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Essentials of, , Medical Physiology
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®, , Jaypee Brothers Medical Publishers (P) Ltd, Headquarters, Jaypee Brothers Medical Publishers (P) Ltd, 4838/24, Ansari Road, Daryaganj, New Delhi 110 002, India, Phone: +91-11-43574357, Fax: +91-11-43574314, Email: jaypee@jaypeebrothers.com, , Overseas Offices, J.P. Medical Ltd, 83 Victoria Street, London, SW1H 0HW (UK), Phone: +44-2031708910, Fax: +02-03-0086180, Email: info@jpmedpub.com, Jaypee Brothers Medical Publishers (P) Ltd, 17/1-B Babar Road, Block-B, Shaymali, Mohammadpur, Dhaka-1207, Bangladesh, Mobile: +08801912003485, Email: jaypeedhaka@gmail.com, , Jaypee-Highlights Medical Publishers Inc., City of Knowledge, Bld. 237, Clayton, Panama City, Panama, Phone: + 507-301-0496, Fax: + 507-301-0499, Email: cservice@jphmedical.com, Jaypee Brothers Medical Publishers (P) Ltd, Shorakhute, Kathmandu, Nepal, Phone: +00977-9841528578, Email: jaypee.nepal@gmail.com, , Website: www.jaypeebrothers.com, Website: www.jaypeedigital.com, © 2012, Jaypee Brothers Medical Publishers, All rights reserved. No part of this book may be reproduced in any form or by any means without the prior permission of the publisher., Inquiries for bulk sales may be solicited at: jaypee@jaypeebrothers.com, This book has been published in good faith that the contents provided by the authors contained herein are original, and is intended for educational, purposes only. While every effort is made to ensure accuracy of information, the publisher and the authors specifically disclaim any damage, liability,, or loss incurred, directly or indirectly, from the use or application of any of the contents of this work. If not specifically stated, all figures and tables, are courtesy of the authors. Where appropriate, the readers should consult with a specialist or contact the manufacturer of the drug or device., Essentials of Medical Physiology, First Edition: 1999, Second Edition: 2000, Third Edition: 2004, Fourth Edition: 2006, Fifth Edition: 2010, Sixth Edition: 2012, ISBN 978-93-5025-936-8, Printed at
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Dedicated to, Our beloved students
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Foreword to the Sixth Edition, Madha Medical college & ReseaRch institute, Approved by Medical Council of India, New Delhi,, Affiliated to Tamil Nadu Dr. M.G.R. Medical University, Chennai, Proc. No. AffIn. III (3)/4206/2010, Thandalam, Kovur (Near Porur), Chennai-600 122. Phone : 044 - 2478 0333, 2478 0055, E-mail: madhahospital@gmail.com, , Dr S MaDaN KuMar MD, Dip. A & E, Director, , It is my privilege and pleasure to give this foreword to sixth edition of the textbook Essentials of Medical Physiology, written by two of our dedicated and renowned teachers Dr K Sembulingam and Dr Prema Sembulingam. Since, the publication of first edition in the year 1999, this book has been accepted by the faculty of many universities in, and out of country. It has become popular among medical, dental and paramedical students because of its elegant, presentation, simple language and clear illustrations with diagrams, flow charts and tables., The authors have taken concerted efforts to improve the contents and update the information in every subsequent, edition of this book. This sixth edition with newly formatted and updated tables, flow charts and self-explanatory, diagrams will help the students in better understanding and performance in various types of examinations. Clinical, physiology with updated information in this edition will help the students for their clinical knowledge to a great extent., I congratulate Dr K Sembulingam and Dr Prema Sembulingam on their great effort in bringing sixth edition of this, book., , Dr S Madan Kumar MD, Dip. A & E, Director, Madha Medical College & Research Institute, Thandalam, Kovur (Near Porur), Chennai, Tamil Nadu, India
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Foreword to the First Edition, sRi RaMachandRa Medical college and ReseaRch institute, (deeMed univeRsity), 1, RAMAChANDRA NAGAR, PoRUR, ChENNAI-600 116, , Dr TK ParTha SaraThy FRCs (C) FACs, Diplomate of the American Board of surgery, vICE-ChANCElloR, , off, Fax, , : 4828027-29, 31-33, : 091-44-48277008, , Telex : 41-25050 PCo IN, , It is indeed with a great sense of pleasure and privilege that I give this foreword to the book Essentials of Medical, Physiology written by two of our dedicated teachers Dr K Sembulingam and Dr Prema Sembulingam. The students, have always appreciated the efforts of these two teachers and their ability to make physiology easily comprehended, and interesting. Why one more book in physiology, is what I asked myself first before I reviewed the book. The book, has been largely directed to the broad and specific needs of the undergraduate students, and simplicity and clarity, have been emphasized. The students can easily assimilate the logical sequence in which the subjects have been, presented not only for them to understand the same but also perform well in the various types of objective and, routine examinations., Several readily understandable diagrams and tables have been included to make subject comprehension and, revision easy. Applied physiology, clinical importance and altered situations in pediatrics, geriatrics and pregnancy, have been well brought out. The approach utilized in dealing with the subject of physiology would be appreciated, by other teachers as well. I have no doubts that this will be a valuable addition to the armamentarium of a student, of physiology who is preparing for examination and is seeking a strong foundation to build further on., Here at Sri Ramachandra Medical College and Research Institute (Deemed University), Chennai, Tamil Nadu, India,, the faculty involved in writing and editing books of this nature are greatly appreciated, and I as its Vice-Chancellor, wish to congratulate the Sembulingams on their great effort., , TK Partha Sarathy FRCS (C) FACS, Diplomate of the American Board of Surgery, Vice-Chancellor, Sri Ramachandra Medical College and Research, Institute (Deemed University), Porur, Chennai, Tamil Nadu, India
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Preface to the Sixth Edition, With this Sixth edition, Sembulingam’s Essentials of Medical Physiology enters into its second decade and the core, subject matter with updated physiological information remain as green as ever. We live in an era where the thirst, for knowledge and urge for learning is so much increased that even a layman knows the fundamentals of common, disorders like diabetes mellitus, hypertension, jaundice, etc. So, it becomes doubly important to fulfill the expectations, of the educated mass, especially in medical field., We are humbly thankful and heavenly happy for the popularity of this book among the undergraduate and, postgraduate students of medical, dental and paramedical courses, doctors and other health professionals in and, out of our country., Like many other successful textbooks, this book also has sailed through the years smoothly, fruitfully and, successfully. May be because, it meets the needs of every group of the readers. Students are happy because it is, student-friendly while reading, and exam-friendly while revising. Knowledge seekers are happy because they get, the updated and recent developments in the field of physiology. Doctors are happy because applied aspects are, covered adequately., Our thirst for improving this textbook is growing every year by seeing outright acceptance of this book by the, students, and the appreciation and overwhelming support given by our fellow teachers. The most comments and, the suggestions, we receive from our readers, are responsible for better shaping of this book in every edition., This edition is enriched with addition of many more flow charts, tables and descriptive diagrams to make the, subject matter easier and approachable for all class of students. Many chapters are upgraded as per the suggestions, from our colleagues and fellow teachers from various institutes and universities in and out of India., Our thirst for improving this book is still alive. The improvement is possible only by the comments and suggestions, expressed by the readers. So, we welcome the opinions, comments and valuable suggestions from one and all who, happen to come across this book., , K Sembulingam, ksembu@yahoo.com, , Prema Sembulingam, prema_sembu@yahoo.com
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Preface to the First Edition, The need for having a simple book with basic principles of Medical Physiology has been felt since long. A sincere and, maiden attempt has been made with the idea of fulfilling the requirements of present-day curriculum. The script of, the book is formatted in such a way that it will be suitable not only for medical students, but also for dental students, and the students of allied health subjects like Physiotherapy, Occupational Therapy, Pharmacy, Nursing, Speech,, Hearing and Language, etc., Written in a textbook form, this book encompasses the knowledge of basic principles of physiology in each system., An attempt is also made to describe the applied physiology in each system., To give an idea of the matters to be studied, the topics are listed at the beginning of each chapter. Most of the, figures are given in schematic form to enable students to understand and reproduce the facts. The probable questions, given for each section will help the students preparing for examinations. However, it will be ideal for the students to, read each section thoroughly before referring to the questions., We will be very happy to receive opinions, comments and valuable suggestions from all our senior colleagues,, fellow teachers and students so that, every aspect of the book can be reviewed in succeeding editions., , K Sembulingam, Prema Sembulingam
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Acknowledgments, We express our profound gratitude to Late Mr NPV Ramasamy Udayar, Founder Chancellor, Sri Ramachandra, Medical College and Research Institute (Deemed University), Chennai, Tamil Nadu, India for his keen interest in all, the academic activities of the faculty members., We would like to express our sincere gratitude to Sri VR Venkatachalam, the Chancellor of Sri Ramachandra, Medical College and Research Institute (Deemed University) for accepting to grace the occasion of ‘Book Releasing, Ceremony’ of Essentials of Medical Physiology—first edition and for releasing the book. We are very much thankful, to the former Vice-Chancellor of this University Dr TK Partha Sarathy, who honored us by attending the function and, received the first copy of the book. We are also overwhelmed by his magnanimity for his encouragement and for, going through the entire script before giving the foreword., We sincerely thank Mrs Radha Venkatachalam, Registrar and Administrative Director, Sri Ramachandra Medical, College and Research Institute (Deemed University), who always encouraged the faculty of the university for, publications., We thank Dr Sylvia Walter, Professor Emeritus, Department of Physiology, Sri Ramachandra Medical College, and Research Institute (Deemed University), who is the inspiration for us to bring out this book. We are also indebted, to her for giving many valuable clues to modify the script in many chapters. Our special thanks to Dr V Srinivasan,, Former Professor and Head, Department of Physiology, Sri Ramachandra Medical College and Research Institute, (Deemed University) for his strong belief in this project, constant encouragement and valuable suggestions. We are, very much grateful to Dr V Srinivasan for his keen interest and valuable suggestions for upgrading the script in each, edition., We thank all our fellow teachers and senior professors from various institutes and universities in and out of India, for their comments and suggestions, which enabled us to bring out each edition of the book successfully., We are deeply indebted to our students of Sri Ramachandra Medical College and Research Institute (Deemed, University), Chennai, Tamil Nadu, India and MR Medical College, Gulbarga, Karnataka, India who were the spirit, behind the idea of bringing out this book., Our special thanks to Dr M Chandrasekar, Vice-Principal and Head, Department of Physiology, Meenakshi Medical, College, Kanchipuram, Tamil Nadu, India for writing a review article on this book in the Journal ‘Biomedicine’, (Vol 20, No. 1). Many valuable suggestions from him enabled us to upgrade the book in each edition., We are grateful to Professor Mafauzy Mohamad, Director, Health Campus, Universiti Sains Malaysia, Kelantan,, Malaysia for providing the photos of endocrine disorder patients. We are thankful to Dr Nivaldo Medeiros, Former, Director of Hematology and Cytology Services, Central Laboratory, University of Säo Paulo, School of Medicine,, USA for giving us the hematology pictures., Our profound thanks are due to Dr S Peter, Founder and Chairman, Madha Group of Academic Institutions for, the recognition, appreciation and encouragement given to us in bringing out this edition. We are thankful to, Dr S Madan Kumar, Director, Madha Medical College & Research Institute for his keen interest in publishing this, edition. We also thank him for accepting and rendering foreword for this edition. We thank Dr K Gajendran, Principal,, Madha Medical College & Research Institute for his constant encouragement in bringing out this edition., We are thankful to Shri Jitendar P Vij (CEO), Mr Tarun Duneja (Director-Publishing) and Mr KK Raman (Production, Manager) of M/s Jaypee Brothers Medical Publishers (P) Ltd, New Delhi, India for publishing the book in the same, format as we wanted. We thank Ms Chetna Malhotra Vohra (Senior Business Executive Manager) for coordinating, the processing of this edition. We thank Ms Sajini SV (Project Leader), Ms Hemalata Malini B and Mr Samiulla (DTP, Operators); Ms Nandini N, Ms Ramya VR, Ms Bhavya M, and Ms Nikita G (Proofreaders) of Bengaluru Production, Unit, M/s Jaypee Brothers Medical Publishers (P) Ltd, Bengaluru Branch, for their wholehearted contribution while, formatting the book. We also thank Ms Shilpa K Bhat (Graphic Designer), of Bengaluru Production Unit for making, the figures attractive.
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Special Acknowledgments, We sincerely acknowledge the following fellow teachers for their valuable suggestions. All the points suggested by, them were acknowledged and incorporated in this edition., 1. Dr M Chandrasekar, Vice Principal and Head, Department of Physiology, Meenakshi Medical College, Kanchipuram, Tamil Nadu, India, 2. Dr P Sai Kumar, Vice Principal and Professor, Department of Physiology, Sri Balaji Medical College and Hospital, Chennai, Tamil Nadu, India, 3. Dr B Vishwanatha Rao, Professor, Department of Physiology, Madras Medical College, Chennai, Tamil Nadu, India, 4. Dr K Sarayu, Professor and Head, Department of Physiology, KAT Viswanathan Government Medical College, Trichy, Tamil Nadu, India, 5. Dr D Venkatesh, Professor, Department of Physiology, MS Ramaiah Medical College, Bengaluru, Karnataka, India, , 6. Dr S Manikandan, Associate Professor, Department of Physiology, Tagore Medical College, Chennai, Tamil Nadu, India, 7. Dr NV Mishra, Associate Professor, Department of Physiology, Medical College, Nagpur (MS), Maharashtra, India, 8. Dr KS Udayashankar, Professor and Head, Department of Physiology, Sri Rajarajeshwari Medical College and Hospital, Bengaluru, Karnataka, India, 9. Dr MG Hymavthi, Professor, Department of Physiology, Sri Rajarajeshwari Medical College and Hospital, Bengaluru, Karnataka, India
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Contents, SECTIoN 1, GENERAL PHySIoLoGy, 1., 2., 3., 4., 5., , Cell .....................................................................................................................................3, Cell Junctions .................................................................................................................22, Transport through Cell Membrane ................................................................................27, Homeostasis ...................................................................................................................38, Acid-Base Balance .........................................................................................................42, , SECTIoN 2, BLooD AND BoDy FLUIDS, 6., 7., 8., 9., 10., 11., 12., 13., 14., 15., 16., 17., 18., 19., 20., 21., 22., 23., 24., 25., 26., 27., , Body Fluids .....................................................................................................................51, Blood ...............................................................................................................................58, Plasma Proteins..............................................................................................................61, Red Blood Cells ..............................................................................................................66, Erythropoiesis ................................................................................................................71, Hemoglobin and Iron Metabolism .................................................................................77, Erythrocyte Sedimentation Rate ...................................................................................83, Packed Cell Volume and Blood Indices........................................................................86, Anemia.............................................................................................................................89, Hemolysis and Fragility of Red Blood Cells ................................................................95, White Blood Cells ...........................................................................................................97, Immunity........................................................................................................................107, Platelets .........................................................................................................................122, Hemostasis ...................................................................................................................127, Coagulation of Blood ...................................................................................................129, Blood Groups................................................................................................................139, Blood Transfusion ........................................................................................................146, Blood Volume................................................................................................................148, Reticuloendothelial System and Tissue Macrophage...............................................151, Spleen ............................................................................................................................153, Lymphatic System and Lymph ....................................................................................155, Tissue Fluid and Edema ..............................................................................................159
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xviii, , Essentials of Medical Physiology, , SECTIoN 3, MUSCLE PHySIoLoGy, 28., 29., 30., 31., 32., 33., 34., 35., , Classification of Muscles.............................................................................................167, Structure of Skeletal Muscle .......................................................................................169, Properties of Skeletal Muscle......................................................................................176, Changes during Muscular Contraction ......................................................................188, Neuromuscular Junction .............................................................................................200, Smooth Muscle .............................................................................................................204, Electromyogram and Disorders of Skeletal Muscle ..................................................210, Endurance of Muscle ...................................................................................................214, , SECTIoN 4, DIGESTIVE SySTEM, 36., 37., 38., 39., 40., 41., 42., 43., 44., 45., 46., 47., , Introduction to Digestive System ...............................................................................219, Mouth and Salivary Glands .........................................................................................223, Stomach ........................................................................................................................230, Pancreas........................................................................................................................241, Liver and Gallbladder ...................................................................................................249, Small Intestine ..............................................................................................................261, Large Intestine ..............................................................................................................266, Movements of Gastrointestinal Tract .........................................................................270, Gastrointestinal Hormones .........................................................................................281, Digestion, Absorption and Metabolism of Carbohydrates .......................................287, Digestion, Absorption and Metabolism of Proteins ..................................................290, Digestion, Absorption and Metabolism of Lipids ......................................................292, , SECTIoN 5, RENAL PHySIoLoGy AND SKIN, 48., 49., 50., 51., 52., 53., 54., 55., 56., , Kidney............................................................................................................................301, Nephron .........................................................................................................................304, Juxtaglomerular Apparatus .........................................................................................309, Renal Circulation ..........................................................................................................312, Urine Formation ............................................................................................................315, Concentration of Urine.................................................................................................325, Acidification of Urine and Role of Kidney in Acid-Base Balance ............................330, Renal Function Tests ...................................................................................................333, Renal Failure .................................................................................................................337
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Contents, , 57., 58., 59., 60., 61., 62., 63., , Micturition .....................................................................................................................339, Dialysis and Artificial Kidney ......................................................................................346, Diuretics ........................................................................................................................348, Structure of Skin...........................................................................................................351, Functions of Skin .........................................................................................................354, Glands of Skin ..............................................................................................................356, Body Temperature ........................................................................................................359, , SECTIoN 6, ENDoCRINoLoGy, 64., 65., 66., 67., 68., 69., 70., 71., 72., 73., , Introduction to Endocrinology ....................................................................................367, Hormones ......................................................................................................................371, Pituitary Gland ..............................................................................................................375, Thyroid Gland ...............................................................................................................388, Parathyroid Glands and Physiology of Bone ............................................................399, Endocrine Functions of Pancreas ..............................................................................415, Adrenal Cortex ..............................................................................................................425, Adrenal Medulla ............................................................................................................439, Endocrine Functions of other organs .......................................................................444, Local Hormones ...........................................................................................................447, , SECTIoN 7, REPRoDUCTIVE SySTEM, 74., 75., 76., 77., 78., 79., 80., 81., 82., 83., 84., 85., 86., 87., 88., , Male Reproductive System ..........................................................................................455, Seminal Vesicles...........................................................................................................467, Prostate Gland ..............................................................................................................468, Semen ............................................................................................................................470, Female Reproductive System .....................................................................................473, ovary .............................................................................................................................476, Menstrual Cycle ............................................................................................................482, ovulation .......................................................................................................................492, Menopause ....................................................................................................................494, Infertility .......................................................................................................................496, Pregnancy and Parturition...........................................................................................498, Placenta .........................................................................................................................505, Pregnancy Tests ...........................................................................................................508, Mammary Glands and Lactation .................................................................................510, Fertility Control .............................................................................................................513, , xix
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xx, , Essentials of Medical Physiology, , SECTIoN 8, CARDIoVASCULAR SySTEM, 89., 90., 91., 92., 93., 94., 95., 96., 97., 98., 99., 100., 101., 102., 103., 104., 105., 106., 107., 108., 109., 110., 111., 112., 113., 114., 115., 116., 117., , Introduction to Cardiovascular System .....................................................................519, Properties of Cardiac Muscle ......................................................................................525, Cardiac Cycle ................................................................................................................533, Heart Sounds ................................................................................................................544, Cardiac Murmur ............................................................................................................549, Electrocardiogram (ECG).............................................................................................551, Vector.............................................................................................................................558, Arrhythmia ....................................................................................................................562, Effect of Changes in Electrolyte Concentration on Heart ........................................570, Cardiac output..............................................................................................................572, Heart-Lung Preparation ...............................................................................................582, Cardiac Function Curves .............................................................................................584, Heart Rate......................................................................................................................587, Hemodynamics .............................................................................................................595, Arterial Blood Pressure ...............................................................................................602, Venous Pressure ..........................................................................................................617, Capillary Pressure ........................................................................................................620, Arterial Pulse ................................................................................................................622, Venous Pulse ................................................................................................................627, Coronary Circulation ....................................................................................................629, Cerebral Circulation .....................................................................................................634, Splanchnic Circulation.................................................................................................638, Capillary Circulation.....................................................................................................640, Circulation through Skeletal Muscle ..........................................................................644, Cutaneous Circulation .................................................................................................646, Fetal Circulation and Respiration ...............................................................................648, Hemorrhage ..................................................................................................................651, Circulatory Shock and Heart Failure ..........................................................................654, Cardiovascular Adjustments during Exercise ...........................................................664, , SECTIoN 9, RESPIRAToRy SySTEM AND ENVIRoNMENTAL PHySIoLoGy, 118., 119., 120., 121., , Physiological Anatomy of Respiratory Tract .............................................................673, Pulmonary Circulation .................................................................................................678, Mechanics of Respiration ............................................................................................682, Pulmonary Function Tests...........................................................................................690
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Contents, , 122., 123., 124., 125., 126., 127., 128., 129., 130., 131., 132., , Ventilation .....................................................................................................................700, Inspired Air, Alveolar Air and Expired Air ..................................................................703, Exchange of Respiratory Gases .................................................................................705, Transport of Respiratory Gases .................................................................................711, Regulation of Respiration ............................................................................................716, Disturbances of Respiration........................................................................................723, High Altitude and Space Physiology ..........................................................................737, Deep Sea Physiology ...................................................................................................743, Effects of Exposure to Cold and Heat ........................................................................746, Artificial Respiration ....................................................................................................749, Effects of Exercise on Respiration .............................................................................751, , SECTIoN 10, NERVoUS SySTEM, 133., 134., 135., 136., 137., 138., 139., 140., 141., 142., 143., 144., 145., 146., 147., 148., 149., 150., 151., 152., 153., 154., 155., 156., 157., , Introduction to Nervous System .................................................................................757, Neuron ...........................................................................................................................759, Classification of Nerve Fibers .....................................................................................764, Properties of Nerve Fibers...........................................................................................766, Degeneration and Regeneration of Nerve Fibers ......................................................770, Neuroglia .......................................................................................................................773, Receptors ......................................................................................................................775, Synapse .........................................................................................................................780, Neurotransmitters ........................................................................................................787, Reflex Activity ...............................................................................................................795, Spinal Cord ...................................................................................................................803, Somatosensory System and Somatomotor System .................................................828, Physiology of Pain .......................................................................................................838, Brainstem ......................................................................................................................844, Thalamus .......................................................................................................................847, Internal Capsule............................................................................................................853, Hypothalamus ...............................................................................................................855, Cerebellum ....................................................................................................................863, Basal Ganglia ................................................................................................................878, Cerebral Cortex.............................................................................................................884, Limbic System ..............................................................................................................898, Reticular Formation......................................................................................................901, Preparations of Animals for Experimental Studies ...................................................906, Proprioceptors ..............................................................................................................908, Posture and Equilibrium ..............................................................................................913, , xxi
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158., 159., 160., 161., 162., 163., 164., , Vestibular Apparatus ....................................................................................................919, Electroencephalogram (EEG) ......................................................................................929, Physiology of Sleep .....................................................................................................931, Epilepsy .........................................................................................................................935, Higher Intellectual Functions ......................................................................................937, Cerebrospinal Fluid (CSF) ...........................................................................................949, Autonomic Nervous System (ANS).............................................................................954, , SECTIoN 11, SPECIAL SENSES, 165., 166., 167., 168., 169., 170., 171., 172., 173., 174., 175., 176., 177., , Structure of the Eye .....................................................................................................965, Visual Process ..............................................................................................................978, Field of Vision ...............................................................................................................987, Visual Pathway .............................................................................................................989, Pupillary Reflexes.........................................................................................................994, Color Vision ..................................................................................................................999, Errors of Refraction....................................................................................................1004, Structure of Ear ..........................................................................................................1007, Auditory Pathway .......................................................................................................1013, Mechanism of Hearing ...............................................................................................1016, Auditory Defects .........................................................................................................1022, Sensation of Taste ......................................................................................................1024, Sensation of Smell .....................................................................................................1028, , • Index ..................................................................................................................................1033
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Introduction, Physiology is the most fascinating and ancient branch of science. It is fascinating because, it unfolds the mystery of, complicated functional aspects of individual organs in the body. It is ancient because, it exists ever since the origin, of life. Even before knowing the language, culture and society, man knew about the hunger, thirst, pain and fear, which are the basics of physiology., Physiology is defined as the study of functions of various systems and different organs of the body. Physiology, is of different types namely, Human Physiology, Animal Physiology and Plant Physiology. Human Physiology and, Animal Physiology are very much inter-related. Knowledge of Human Physiology is essential to understand the other, allied subjects like Biochemistry, Pharmacology, Pathology, Medicine, etc. However, it is worthwhile to have a brief, knowledge of anatomy of different systems and various organs to understand the principles of Human Physiology., The basic physiological functions include, provision of oxygen and nutrients, removal of metabolites and other, waste products, maintenance of blood pressure and body temperature, hunger and thirst, locomotor functions, special, sensory functions, reproduction and the higher intellectual functions like learning and memory., In the unicellular organisms, all the physiological functions are carried out by simple diffusion through the cell, membrane. Because of the evolutionary and ecological changes over the years, individual system is developed for, each function such as digestive system, cardiovascular system, respiratory system, excretory system, etc. Every, system in the body is independent structurally and functionally yet, all the systems are interdependent., Human Physiology is usually studied under the following headings:, 1., 2., 3., 4., 5., 6., 7., 8., 9., 10., 11., , General Physiology, Blood and Body Fluids, Muscle Physiology, Digestive System, Renal Physiology and Excretion, Endocrinology, Reproductive System, Cardiovascular System, Respiratory System and Environmental Physiology, Nervous System, Special Senses
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Section, , 1, , 1., 2., 3., 4., 5., , General Physiology, , Cell .............................................................................................................. 3, Cell Junctions ............................................................................................ 22, Transport through Cell Membrane ............................................................ 27, Homeostasis ............................................................................................. 38, Acid-base Balance .................................................................................... 42
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Chapter, , Cell, , 1, , , , , , , , , , , , , , , , , , , , , INTRODUCTION, STRUCTURE OF THE CELL, CELL MEMBRANE, CYTOPLASM, ORGANELLES IN CYTOPLASM, ORGANELLES WITH LIMITING MEMBRANE, ORGANELLES WITHOUT LIMITING MEMBRANE, NUCLEUS, DEOXYRIBONUCLEIC ACID, GENE, RIBONUCLEIC ACID, GENE EXPRESSION, GROWTH FACTORS, CELL DEATH, CELL ADAPTATION, CELL DEGENERATION, CELL AGING, STEM CELLS, , INTRODUCTION, CELL, All the living things are composed of cells. A single cell, is the smallest unit that has all the characteristics of life., Cell is defined as the structural and functional unit of the, living body., General Characteristics of Cell, Each cell in the body:, 1. Needs nutrition and oxygen, 2. Produces its own energy necessary for its growth,, repair and other activities, 3. Eliminates carbon dioxide and other metabolic wastes, 4. Maintains the medium, i.e. the environment for its, survival, , 5. Shows immediate response to the entry of invaders, like bacteria or toxic substances into the body, 6. Reproduces by division. There are some exceptions, like neuron, which do not reproduce., TISSUE, Tissue is defined as the group of cells having similar, function. There are many types of tissues in the body. All, the tissues are classified into four major types which are, called the primary tissues. The primary tissues include:, 1. Muscle tissue (skeletal muscle, smooth muscle and, cardiac muscle), 2. Nervous tissue (neurons and supporting cells), 3. Epithelial tissue (squamous, columnar and cuboidal, epithelial cells), 4. Connective tissue (connective tissue proper, cartilage, bone and blood).
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4, , Section 1 t General Physiology, , ORGAN, , CELL MEMBRANE, , An organ is defined as the structure that is formed by, two or more primary types of tissues, which execute the, functions of the organ. Some organs are composed of all, the four types of primary tissues. The organs are of two, types, namely tubular or hollow organs and compact or, parenchymal organs. Some of the organs in the body are, brain, heart, lungs, stomach, intestine, liver, gallbladder,, pancreas, kidneys, endocrine glands, etc., , Cell membrane is a protective sheath, enveloping the, cell body. It is also known as plasma membrane or, plasmalemma. This membrane separates the fluid out, side the cell called extracellular fluid (ECF) and the fluid, inside the cell called intracellular fluid (ICF). The cell, membrane is a semipermeable membrane. So, there is, free exchange of certain substances between ECF and, ICF. Thickness of the cell membrane varies from 75 to, 111Å (Fig. 1.2)., , SYSTEM, The organ system is defined as group of organs that work, together to carry out specific functions of the body., Each system performs a specific function. Digestive, system is concerned with digestion of food particles., Excretory system eliminates unwanted substances., Cardiovascular system is responsible for transport of, substances between the organs. Respiratory system, is concerned with the supply of oxygen and removal of, carbon dioxide. Reproductive system is involved in the, reproduction of species. Endocrine system is concerned, with growth of the body and regulation and maintenance, of normal life. Musculoskeletal system is responsible for, stability and movements of the body. Nervous system, controls the locomotion and other activities including the, intellectual functions., , STRUCTURE OF THE CELL, Each cell is formed by a cell body and a membrane, covering the cell body called the cell membrane. Cell, body has two parts, namely nucleus and cytoplasm, surrounding the nucleus (Fig. 1.1). Thus, the structure, of the cell is studied under three headings:, 1. Cell membrane, 2. Cytoplasm, 3. Nucleus., , FIGURE 1.1: Structure of the cell, , COMPOSITION OF CELL MEMBRANE, Cell membrane is composed of three types of substances:, 1. Proteins (55%), 2. Lipids (40%), 3. Carbohydrates (5%)., STRUCTURE OF CELL MEMBRANE, On the basis of structure, cell membrane is called a unit, membrane or a three-layered membrane. The electron, microscopic study reveals three layers of cell membrane,, namely, one central electron-lucent layer and two electron-dense layers. The two electron-dense layers are, placed one on either side of the central layer. The central, layer is a lipid layer formed by lipid substances. The, other two layers are protein layers formed by proteins., Cell membrane contains some carbohydrate molecules, also., Structural Model of the Cell Membrane, 1. Danielli-Davson model, ‘DanielliDavson model’ was the first proposed basic, model of membrane structure. It was proposed by, James F Danielli and Hugh Davson in 1935. And it was, accepted by scientists for many years. This model was, basically a ‘sandwich of lipids’ covered by proteins on, both sides., , FIGURE 1.2: Diagram of the cell membrane
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Chapter 1 t Cell, 2. Unit membrane model, In 1957, JD Robertson replaced ‘DanielliDavson model’, by ‘Unit membrane model’ on the basis of electron, microscopic studies., , 5, , oily structures and cholesterol helps to ‘pack’ the, phospholipids in the membrane. So, cholesterol is, responsible for the structural integrity of lipid layer of the, cell membrane., , 3. Fluid mosaic model, , Functions of Lipid Layer in Cell Membrane, , Later in 1972, SJ Singer and GL Nicholson proposed ‘The, fluid mosaic model’. According to them, the membrane, is a fluid with mosaic of proteins (mosaic means pattern, formed by arrangement of different colored pieces of, stone, tile, glass or other such materials). This model, is accepted by the scientists till now. In this model, the, proteins are found to float in the lipid layer instead of, forming the layers of the sandwich-type model., , Lipid layer of the cell membrane is a semipermeable, membrane and allows only the fat-soluble substances, to pass through it. Thus, the fat-soluble substances like, oxygen, carbon dioxide and alcohol can pass through, this lipid layer. The water-soluble substances such as, glucose, urea and electrolytes cannot pass through this, layer., Protein Layers of the Cell Membrane, , Lipid Layers of the Cell Membrane, The central lipid layer is a bilayered structure. This is, formed by a thin film of lipids. The characteristic feature, of lipid layer is that, it is fluid in nature and not a solid, structure. So, the portions of the membrane move from, one point to another point along the surface of the cell., The materials dissolved in lipid layer also move to all, areas of the cell membrane., Major lipids are:, 1. Phospholipids, 2. Cholesterol., 1. Phospholipids, Phospholipids are the lipid substances containing phosphorus and fatty acids. Aminophospholipids, sphingomyelins, phosphatidylcholine, phosphatidyletholamine,, phosphatidylglycerol, phosphatidylserine and phosphatidylinositol are the phospholipids present in lipid, , layer of cell membrane., Phospholipid molecules are arranged in two layers, (Fig. 1.3). Each phospholipid molecule resembles the, headed pin in shape. The outer part of the phospholipid, molecule is called the head portion and the inner portion, is called the tail portion., Head portion is the polar end and it is soluble in, water and has strong affinity for water (hydrophilic). Tail, portion is the non-polar end. It is insoluble in water and, repelled by water (hydrophobic)., Two layers of phospholipids are arranged in such a, way that the hydrophobic tail portions meet in the center, of the membrane. Hydrophilic head portions of outer, layer face the ECF and those of the inner layer face ICF, (cytoplasm)., , Protein layers of the cell membrane are electron-dense, layers. These layers cover the two surfaces of the, central lipid layer. Protein layers give protection to the, central lipid layer. The protein substances present in, these layers are mostly glycoproteins., Protein molecules are classified into two categories:, 1. Integral proteins or transmembrane proteins., 2. Peripheral proteins or peripheral membrane, proteins., 1. Integral proteins, Integral or transmembrane proteins are the proteins that, pass through entire thickness of cell membrane from one, side to the other side. These proteins are tightly bound, with the cell membrane., Examples of integral protein:, i. Cell adhesion proteins, ii. Cell junction proteins, iii. Some carrier (transport) proteins, iv. Channel proteins, v. Some hormone receptors, vi. Antigens, vii. Some enzymes., , 2. Cholesterol, Cholesterol molecules are arranged in between the, phospholipid molecules. Phospholipids are soft and, , FIGURE 1.3: Lipids of the cell membrane
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6, , Section 1 t General Physiology, , 2. Peripheral proteins, Peripheral proteins or peripheral membrane proteins, are the proteins which are partially embedded in the, outer and inner surfaces of the cell membrane and do, not penetrate the cell membrane. Peripheral proteins, are loosely bound with integral proteins or lipid layer of, cell membrane. So, these protein molecules dissociate, readily from the cell membrane., Examples of peripheral proteins:, i. Proteins of cytoskeleton, ii. Some carrier (transport) proteins, iii. Some enzymes., Functions of Proteins in Cell Membrane, 1. Integral proteins provide the structural integrity of, the cell membrane, 2. Channel proteins help in the diffusion of watersoluble substances like glucose and electrolytes, 3. Carrier or transport proteins help in the transport of, substances across the cell membrane by means of, active or passive transport, 4. Pump: Some carrier proteins act as pumps, by, which ions are transported actively across the cell, membrane, 5. Receptor proteins serve as the receptor sites for, hormones and neurotransmitters, 6. Enzymes: Some of the protein molecules form the, enzymes and control chemical (metabolic) reactions, within the cell membrane, 7. Antigens: Some proteins act as antigens and induce, the process of antibody formation, 8. Cell adhesion molecules or the integral proteins are, responsible for attachment of cells to their neighbors, or to basal lamina., , 3. Some carbohydrate molecules function as the, receptors for some hormones., FUNCTIONS OF CELL MEMBRANE, 1. Protective function: Cell membrane protects the, cytoplasm and the organelles present in the cytoplasm, 2. Selective permeability: Cell membrane acts as a, semipermeable membrane, which allows only some, substances to pass through it and acts as a barrier, for other substances, 3. Absorptive function: Nutrients are absorbed into the, cell through the cell membrane, 4. Excretory function: Metabolites and other waste, products from the cell are excreted out through the, cell membrane, 5. Exchange of gases: Oxygen enters the cell from the, blood and carbon dioxide leaves the cell and enters, the blood through the cell membrane, 6. Maintenance of shape and size of the cell: Cell membrane is responsible for the maintenance of shape, and size of the cell., , CYTOPLASM, Cytoplasm of the cell is the jellylike material formed by, 80% of water. It contains a clear liquid portion called, cytosol and various particles of different shape and, size. These particles are proteins, carbohydrates, lipids, or electrolytes in nature. Cytoplasm also contains many, organelles with distinct structure and function., Cytoplasm is made up of two zones:, 1. Ectoplasm: Peripheral part of cytoplasm, situated, just beneath the cell membrane, 2. Endoplasm: Inner part of cytoplasm, interposed, between the ectoplasm and the nucleus., , Carbohydrates of the Cell Membrane, , ORGANELLES IN CYTOPLASM, , Some of the carbohydrate molecules present in, cell membrane are attached to proteins and form, glycoproteins (proteoglycans). Some carbohydrate, molecules are attached to lipids and form glycolipids., Carbohydrate molecules form a thin and loose, covering over the entire surface of the cell membrane, called glycocalyx., , Cytoplasmic organelles are the cellular structures, embedded in the cytoplasm. Organelles are considered, as small organs of the cell. Some organelles are bound, by limiting membrane and others do not have limiting, membrane (Box 1.1). Each organelle is having a definite, structure and specific functions (Table 1.1)., , Functions of Carbohydrates in Cell Membrance, 1. Carbohydrate molecules are negatively charged and, do not permit the negatively charged substances to, move in and out of the cell, 2. Glycocalyx from the neighboring cells helps in the, tight fixation of cells with one another, , ORGANELLES WITH LIMITING MEMBRANE, ENDOPLASMIC RETICULUM, Endoplasmic reticulum is a network of tubular and, microsomal vesicular structures which are interconnected with one another. It is covered by a limiting membrane, which is formed by proteins and bilayered lipids. The lumen
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Chapter 1 t Cell, BOX 1.1: Cytoplasmic organelles, Organelles with limiting membrane, 1., 2., 3., 4., 5., 6., 7., 8., , Endoplasmic reticulum, Golgi apparatus, Lysosome, Peroxisome, Centrosome and centrioles, Secretory vesicles, Mitochondria, Nucleus, , 7, , between nucleus and cell membrane by connecting the, cell membrane with the nuclear membrane., Types of Endoplasmic Reticulum, , Organelles without limiting membrane, , Endoplasmic reticulum is of two types, namely rough, endoplasmic reticulum and smooth endoplasmic reticulum. Both the types are interconnected and continuous, with one another. Depending upon the activities of the, cells, the rough endoplasmic reticulum changes to, smooth endoplasmic reticulum and vice versa., Rough Endoplasmic Reticulum, , 1. Ribosomes, 2. Cytoskeleton, , of endoplasmic reticulum contains a fluid medium called, endoplasmic matrix. The diameter of the lumen is about, 400 to 700Å. The endoplasmic reticulum forms the link, , It is the endoplasmic reticulum with rough, bumpy or, bead-like appearance. Rough appearance is due to the, attachment of granular ribosomes to its outer surface., Hence, it is also called the granular endoplasmic, , TABLE 1.1: Functions of cytoplasmic organelles, Organelles, , Functions, , Rough endoplasmic reticulum, , 1. Synthesis of proteins, 2. Degradation of wornout organelles, , Smooth endoplasmic reticulum, , 1. Synthesis of lipids and steroids, 2. Role in cellular metabolism, 3. Storage and metabolism of calcium, 4. Catabolism and detoxification of toxic substances, , Golgi apparatus, , 1. Processing, packaging, labeling and delivery of proteins and lipids, , Lysosomes, , 1. Degradation of macromolecules, 2. Degradation of wornout organelles, 3. Removal of excess of secretory products, 4. Secretion of perforin, granzymes, melanin and serotonin, , Peroxisomes, , 1. Breakdown of excess fatty acids, 2. Detoxification of hydrogen peroxide and other metabolic products, 3. Oxygen utilization, 4. Acceleration of gluconeogenesis, 5. Degradation of purine to uric acid, 6. Role in the formation of myelin, 7. Role in the formation of bile acids, , Centrosome, , 1. Movement of chromosomes during cell division, , Mitochondria, , 1. Production of energy, 2. Synthesis of ATP, 3. Initiation of apoptosis, , Ribosomes, , 1. Synthesis of proteins, , Cytoskeleton, , 1. Determination of shape of the cell, 2. Stability of cell shape, 3. Cellular movements, , Nucleus, , 1. Control of all activities of the cell, 2. Synthesis of RNA, 3. Sending genetic instruction to cytoplasm for protein synthesis, 4. Formation of subunits of ribosomes, 5. Control of cell division, 6. Storage of hereditary information in genes (DNA)
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8, , Section 1 t General Physiology, , reticulum (Fig. 1.4). Rough endoplasmic reticulum is, vesicular or tubular in structure., , Functions of Rough Endoplasmic Reticulum, 1. Synthesis of proteins, Rough endoplasmic reticulum is concerned with the, synthesis of proteins in the cell. It is involved with the, synthesis of mainly those proteins which are secreted, from the cells such as insulin from βcells of islets, of Langerhans in pancreas and antibodies from B, lymphocytes., Ribosomes arrange the amino acids into small, units of proteins and transport them into the rough, endoplasmic reticulum. Here, the carbohydrates are, added to the protein units forming the glycosylated, proteins or glycoproteins, which are arranged in the, form of reticular vesicles. These vesicles are transported, mainly to Golgi apparatus for further modification and, processing. Few vesicles are transported to other cytoplasmic organelles., 2. Degradation of worn-out organelles, , FIGURE 1.4: Endoplasmic reticulum, , 3. Storage and metabolism of calcium, Smooth endoplasmic reticulum is the major site of, storage and metabolism of calcium. In skeletal muscle, fibers, it releases calcium which is necessary to trigger, the muscle contraction., , Rough endoplasmic reticulum also plays an important, role in the degradation of worn-out cytoplasmic organelles like mitochondria. It wraps itself around the wornout organelles and forms a vacuole which is often called, the autophagosome. Autophagosome is digested by, lysosomal enzymes (see below for details)., , Smooth endoplasmic reticulum is also concerned, with catabolism and detoxification of toxic substances, like some drugs and carcinogens (cancer-producing, substances) in the liver., , Smooth Endoplasmic Reticulum, , GOLGI APPARATUS, , It is the endoplasmic reticulum with smooth appearance., It is also called agranular reticulum. It is formed by many, interconnected tubules. So, it is also called tubular, , Golgi apparatus or Golgi body or Golgi complex is a, membrane-bound organelle, involved in the processing, of proteins. It is present in all the cells except red blood, cells. It is named after the discoverer Camillo Golgi., Usually, each cell has one Golgi apparatus. Some of the, cells may have more than one Golgi apparatus. Each, Golgi apparatus consists of 5 to 8 flattened membranous, sacs called the cisternae., Golgi apparatus is situated near the nucleus. It has, two ends or faces, namely cis face and trans face. The, cis face is positioned near the endoplasmic reticulum., Reticular vesicles from endoplasmic reticulum enter, the Golgi apparatus through cis face. The trans face, is situated near the cell membrane. The processed, substances make their exit from Golgi apparatus through, trans face (Fig. 1.5)., , endoplasmic reticulum., , Functions of Smooth Endoplasmic Reticulum, 1. Synthesis of non-protein substance, Smooth endoplasmic reticulum is responsible for synthesis of non-protein substances such as cholesterol, and steroid. This type of endoplasmic reticulum is, abundant in cells that are involved in the synthesis of, lipids, phospholipids, lipoprotein substances, steroid, hormones, sebum, etc. In most of the other cells, smooth, endoplasmic reticulum is less extensive than the rough, endoplasmic reticulum., , 4. Catabolism and detoxification, , 2. Role in cellular metabolism, , Functions of Golgi Apparatus, , Outer surface of smooth endoplasmic reticulum contains, many enzymes which are involved in various metabolic, processes of the cell., , Major functions of Golgi apparatus are processing,, packing, labeling and delivery of proteins and other, molecules like lipids to different parts of the cell.
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Chapter 1 t Cell, , 9, , Types of Lysosomes, Lysosomes are of two types:, 1. Primary lysosome, which is pinched off from Golgi, apparatus. It is inactive in spite of having hydrolytic, enzymes, 2. Secondary lysosome, which is the active lysosome., It is formed by the fusion of a primary lysosome with, phagosome or endosome (see below)., Functions of Lysosomes, Lysosomes are often called ‘garbage system’ of the cell, because of their degradation activity. About 50 different, hydrolytic enzymes, known as acid hydroxylases are, present in the lysosomes, through which lysosomes, execute their functions., FIGURE 1.5: Golgi apparatus, , 1. Processing of materials, Vesicles containing glycoproteins and lipids are, transported into Golgi apparatus. Here, the glycoproteins, and lipids are modified and processed., 2. Packaging of materials, All the processed materials are packed in the form of, secretory granules, secretory vesicles and lysosomes,, which are transported either out of the cell or to another, part of the cell. Because of this, Golgi apparatus is called, the ‘post office of the cell’., 3. Labeling and delivery of materials, Finally, the Golgi apparatus sorts out the processed and, packed materials and labels them (such as phosphate, group), depending upon the chemical content for delivery, (distribution) to their proper destinations. Hence, the, Golgi apparatus is called ‘shipping department of the, cell’., , LYSOSOMES, Lysosomes are the membrane-bound vesicular, organelles found throughout the cytoplasm. The lysosomes are formed by Golgi apparatus. The enzymes, synthesized in rough endoplasmic reticulum are, processed and packed in the form of small vesicles in, the Golgi apparatus. Then, these vesicles are pinched, off from Golgi apparatus and become the lysosomes., Among the organelles of the cytoplasm, the, lysosomes have the thickest covering membrane. The, membrane is formed by a bilayered lipid material. It has, many small granules which contain hydrolytic enzymes., , Important lysosomal enzymes, 1. Proteases, which hydrolyze the proteins into amino, acids, 2. Lipases, which hydrolyze the lipids into fatty acids, and glycerides, 3. Amylases, which hydrolyze the polysaccharides, into glucose, 4. Nucleases, which hydrolyze the nucleic acids into, mononucleotides., Mechanism of lysosomal function, Lysosomal functions involve two mechanisms:, 1. Heterophagy: Digestion of extracellular materials, engulfed by the cell via endocytosis, 2. Autophagy: Digestion of intracellular materials such, as worn-out cytoplasmic organelles., Specific functions of lysosomes, 1. Degradation of macromolecules, Macromolecules are engulfed by the cell by means of, endocytosis (phagocytosis, pinocytosis or receptormediated endocytosis: Chapter 3). The macromolecules, such as bacteria, engulfed by the cell via phagocytosis, are called phagosomes or vacuoles. The other, macromolecules taken inside via pinocytosis or, receptor-mediated endocytosis are called endosomes., The primary lysosome fuses with the phagosome or, endosome to form the secondary lysosome. The pH in the, secondary lysosome becomes acidic and the lysosomal, enzymes are activated. The bacteria and the other, macromolecules are digested and degraded by these, enzymes. The secondary lysosome containing these, degraded waste products moves through cytoplasm and
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10, , Section 1 t General Physiology, , fuses with cell membrane. Now the waste products are, eliminated by exocytosis., 2. Degradation of worn-out organelles, The rough endoplasmic reticulum wraps itself around, the worn-out organelles like mitochondria and form, the vacuoles called autophagosomes. One primary, lysosome fuses with one autophagosome to form the, secondary lysosome. The enzymes in the secondary, lysosome are activated. Now, these enzymes digest the, contents of autophagosome., 3. Removal of excess secretory products in the cells, Lysosomes in the cells of the secretory glands remove, the excess secretory products by degrading the secretory, granules., 4. Secretory function – secretory lysosomes, Recently, lysosomes having secretory function, called secretory lysosomes are found in some of the, cells, particularly in the cells of immune system. The, conventional lysosomes are modified into secretory, lysosomes by combining with secretory granules (which, contain the particular secretory product of the cell)., Examples of secretory lysosomes:, i. Lysosomes in the cytotoxic T lymphocytes and, natural killer (NK) cells secrete perforin and, granzymes, which destroy both viral-infected, cells and tumor cells. Perforin is a pore-forming, protein that initiates cell death. Granzymes belong, to the family of serine proteases (enzymes that, dislodge the peptide bonds of the proteins) and, cause the cell death by apoptosis, ii. Secretory lysosomes of melanocytes secrete, melanin, iii. Secretory lysosomes of mast cells secrete, serotonin, which is a vasoconstrictor substance, and inflammatory mediator., PEROXISOMES, Peroxisomes or microbodies are the membrane, limited vesicles like the lysosomes. Unlike lysosomes,, peroxisomes are pinched off from endoplasmic reticulum, and not from the Golgi apparatus. Peroxisomes contain, some oxidative enzymes such as catalase, urate oxidase, and Damino acid oxidase., Functions of Peroxisomes, Peroxisomes:, i. Breakdown the fatty acids by means of a process, called betaoxidation: This is the major function, of peroxisomes, , ii. Degrade the toxic substances such as hydrogen, peroxide and other metabolic products by means, of detoxification. A large number of peroxisomes, are present in the cells of liver, which is the major, organ for detoxification. Hydrogen peroxide is, formed from poisons or alcohol, which enter the, cell. Whenever hydrogen peroxide is produced, in the cell, the peroxisomes are ruptured and, the oxidative enzymes are released. These, oxidases destroy hydrogen peroxide and the, enzymes which are necessary for the production, of hydrogen peroxide, iii. Form the major site of oxygen utilization in the, cells, iv. Accelerate gluconeogenesis from fats, v. Degrade purine to uric acid, vi. Participate in the formation of myelin, viii. Play a role in the formation of bile acids., CENTROSOME AND CENTRIOLES, Centrosome is the membrane-bound cellular organelle, situated almost in the center of cell, close to nucleus., It consists of two cylindrical structures called centrioles, which are made up of proteins. Centrioles are responsible, for the movement of chromosomes during cell division., SECRETORY VESICLES, Secretory vesicles are the organelles with limiting, membrane and contain the secretory substances. These, vesicles are formed in the endoplasmic reticulum and, are processed and packed in Golgi apparatus. Secretory, vesicles are present throughout the cytoplasm. When, necessary, these vesicles are ruptured and secretory, substances are released into the cytoplasm., MITOCHONDRION, Mitochondrion (plural = mitochondria) is a membranebound cytoplasmic organelle concerned with production, of energy. It is a rod-shaped or oval-shaped structure, with a diameter of 0.5 to 1 μ. It is covered by a bilayered, membrane (Fig. 1.6). The outer membrane is smooth and, encloses the contents of mitochondrion. This membrane, contains various enzymes such as acetyl-CoA synthetase, and glycerolphosphate acetyltransferase., The inner membrane is folded in the form of shelf-like, inward projections called cristae and it covers the inner, matrix space. Cristae contain many enzymes and other, protein molecules which are involved in respiration and, synthesis of adenosine triphosphate (ATP). Because of, these functions, the enzymes and other protein molecules
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Chapter 1 t Cell, , 11, , 4. Other functions, Other functions of mitochondria include storage of, calcium and detoxification of ammonia in liver., , ORGANELLES WITHOUT, LIMITING MEMBRANE, FIGURE 1.6: Structure of mitochondrion, , in cristae are collectively known as respiratory chain or, electron transport system., Enzymes and other proteins of respiratory chain, i. Succinic dehydrogenase, ii. Dihydronicotinamide adenine dinucleotide (NADH), dehydrogenase, iii. Cytochrome oxidase, iv. Cytochrome C, v. ATP synthase., Inner cavity of mitochondrion is filled with matrix which, contains many enzymes. Mitochondrion moves freely in, the cytoplasm of the cell. It is capable of reproducing, itself. Mitochondrion contains its own deoxyribonucleic, acid (DNA), which is responsible for many enzymatic, actions. In fact, mitochondrion is the only organelle other, than nucleus, which has its own DNA., Functions of Mitochondrion, 1. Production of energy, Mitochondrion is called the ‘power house’ or ‘power, plant’ of the cell because it produces the energy required, for cellular functions. The energy is produced during the, oxidation of digested food particles like proteins, carbohydrates and lipids by the oxidative enzymes in cristae., During the oxidative process, water and carbon dioxide, are produced with release of energy. The released energy is stored in mitochondria and used later for synthesis, of ATP., , RIBOSOMES, Ribosomes are the organelles without limiting membrane. These organelles are granular and small dot-like, structures with a diameter of 15 nm. Ribosomes are, made up of 35% of proteins and 65% of ribonucleic acid, (RNA). RNA present in ribosomes is called ribosomal, RNA (rRNA). Ribosomes are concerned with protein, synthesis in the cell., Types of Ribosomes, Ribosomes are of two types:, i. Ribosomes that are attached to rough endoplasmic reticulum, ii. Free ribosomes that are distributed in the cytoplasm., Functions of Ribosomes, Ribosomes are called ‘protein factories’ because of, their role in the synthesis of proteins. Messenger RNA, (mRNA) carries the genetic code for protein synthesis, from nucleus to the ribosomes. The ribosomes, in turn, arrange the amino acids into small units of proteins., Ribosomes attached to rough endoplasmic reticulum, are involved in the synthesis of proteins such as the, enzymatic proteins, hormonal proteins, lysosomal proteins and the proteins of the cell membrane., Free ribosomes are responsible for the synthesis of, proteins in hemoglobin, peroxisome and mitochondria., CYTOSKELETON, , 2. Synthesis of ATP, The components of respiratory chain in mitochondrion, are responsible for the synthesis of ATP by utilizing the, energy by oxidative phosphorylation. ATP molecules, diffuse throughout the cell from mitochondrion. Whenever, energy is needed for cellular activity, the ATP molecules, are broken down., 3. Apoptosis, Cytochrome C and second mitochondria-derived activator, of caspases (SMAC)/diablo secreted in mitochondria are, involved in apoptosis (see below)., , Cytoskeleton is the cellular organelle present throughout, the cytoplasm. It determines the shape of the cell and gives, support to the cell. It is a complex network of structures, with varying sizes. In addition to determining the shape of, the cell, it is also essential for the cellular movements and, the response of the cell to external stimuli., Cytoskeleton consists of three major protein, components:, 1. Microtubule, 2. Intermediate filaments, 3. Microfilaments.
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12, , Section 1 t General Physiology, , 1. Microtubules, Microtubules are the straight, hollow and tubular, structures of the cytoskeleton. These organelles without, the limiting membrane are arranged in different bundles., Each tubule has a diameter of 20 to 30 nm. Length of, microtubule varies and it may be 1000 times more than, the thickness., Structurally, the microtubules are formed by bundles, of globular protein called tubulin (Fig. 1.7). Tubulin has, two subunits, namely αsubunit and βsubunit., Functions of microtubules, Microtubules may function alone or join with other, proteins to form more complex structures like cilia,, flagella or centrioles and perform various functions., Microtubules:, i. Determine the shape of the cell, ii. Give structural strength to the cell, iii. Act like conveyer belts which allow the movement, of granules, vesicles, protein molecules and, some organelles like mitochondria to different, parts of the cell, iv. Form the spindle fibers which separate the, chromosomes during mitosis, v. Are responsible for the movement of centrioles, and the complex cellular structures like cilia., , Microfilaments are present throughout the cytoplasm., The microfilaments present in ectoplasm contain, only actin molecules (Fig. 1.9) and those present in, endoplasm contain both actin and myosin molecules., Functions of microfilaments, Microfilaments:, i. Give structural strength to the cell, ii. Provide resistance to the cell against the pulling, forces, iii. Are responsible for cellular movements like, contraction, gliding and cytokinesis (partition of, cytoplasm during cell division)., , NUCLEUS, Nucleus is the most prominent and the largest cellular, organelle. It has a diameter of 10 µ to 22 µ and occupies, about 10% of total volume of the cell., , 2. Intermediate Filaments, Intermediate filaments are the structures that form a, network around the nucleus and extend to the periphery, of the cell. Diameter of each filament is about 10 nm. The, intermediate filaments are formed by ropelike polymers,, which are made up of fibrous proteins (Fig. 1.8)., , FIGURE 1.7: Microtubule, , Subclasses of intermediate filaments, Intermediate filaments are divided into five subclasses:, i. Keratins (in epithelial cells), ii. Glial filaments (in astrocytes), iii. Neurofilaments (in nerve cells), iv. Vimentin (in many types of cells), v. Desmin (in muscle fibers)., , FIGURE 1.8: Intermediate filament, , Functions of intermediate filaments, Intermediate filaments help to maintain the shape of the, cell. These filaments also connect the adjacent cells, through desmosomes., 3. Microfilaments, Microfilaments are long and fine threadlike structures, with a diameter of about 3 to 6 nm. These filaments are, made up of non-tubular contractile proteins called actin, and myosin. Actin is more abundant than myosin., , FIGURE 1.9: Microfilament of ectoplasm
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Chapter 1 t Cell, Nucleus is present in all the cells in the body except, the red blood cells. The cells with nucleus are called, eukaryotes and those without nucleus are known as, prokaryotes. Presence of nucleus is necessary for cell, division., Most of the cells have only one nucleus (uninucleated, cells). Few types of cells like skeletal muscle cells have, many nuclei (multinucleated cells). Generally, the, nucleus is located in the center of the cell. It is mostly, spherical in shape. However, the shape and situation of, nucleus vary in some cells., STRUCTURE OF NUCLEUS, Nucleus is covered by a membrane called nuclear membrane and contains many components. Major components, of nucleus are nucleoplasm, chromatin and nucleolus., Nuclear Membrane, Nuclear membrane is double layered and porous in, nature. This allows the nucleoplasm to communicate with, the cytoplasm. The outer layer of nuclear membrane is, continuous with the membrane of endoplasmic reticulum., The space between the two layers of nuclear membrane, is continuous with the lumen of endoplasmic reticulum., Pores of the nuclear membrane are guarded (lined), by protein molecules. Diameter of the pores is about, 80 to 100 nm. However, it is decreased to about 7 to, 9 nm because of the attachment of protein molecules, with the periphery of the pores. Exchange of materials, between nucleoplasm and cytoplasm occurs through, these pores., Nucleoplasm, Nucleoplasm is a highly viscous fluid that forms the, ground substance of the nucleus. It is similar to cytoplasm, present outside the nucleus., Nucleoplasm surrounds chromatin and nucleolus., It contains dense fibrillar network of proteins called the, nuclear matrix and many substances such as nucleotides, and enzymes. The nuclear matrix forms the structural, framework for organizing chromatin. The soluble liquid, part of nucleoplasm is known as nuclear hyaloplasm., Chromatin, Chromatin is a thread-like material made up of large, molecules of DNA. The DNA molecules are compactly, packed with the help of a specialized basic protein, called histone. So, chromatin is referred as DNA-histone, complex. It forms the major bulk of nuclear material., DNA is a double helix which wraps around central, core of eight histone molecules to form the fundamental, , 13, , packing unit of chromatin called nucleosome. Nucleosomes are packed together tightly with the help of a, histone molecule to form a chromatin fiber., Just before cell division, the chromatin condenses to, form chromosome., Chromosomes, Chromosome is the rod-shaped nuclear structure, that carries a complete blueprint of all the hereditary, characteristics of that species. A chromosome is formed, from a single DNA molecule coiled around histone, molecules. Each DNA contains many genes., Normally, the chromosomes are not visible in the, nucleus under microscope. Only during cell division,, the chromosomes are visible under microscope. This is, because DNA becomes more tightly packed just before, cell division, which makes the chromosome visible, during cell division., All the dividing cells of the body except reproductive, cells contain 23 pairs of chromosomes. Each pair consists, of one chromosome inherited from mother and one from, father. The cells with 23 pairs of chromosomes are called, diploid cells. The reproductive cells called gametes or, sex cells contain only 23 single chromosomes. These, cells are called haploid cells., Nucleolus, Nucleolus is a small, round granular structure of the, nucleus. Each nucleus contains one or more nucleoli., The nucleolus contains RNA and some proteins, which, are similar to those found in ribosomes. The RNA is, synthesized by five different pairs of chromosomes and, stored in the nucleolus. Later, it is condensed to form, the subunits of ribosomes. All the subunits formed in, the nucleolus are transported to cytoplasm through the, pores of nuclear membrane. In the cytoplasm, these, subunits fuse to form ribosomes, which play an essential, role in the formation of proteins., FUNCTIONS OF NUCLEUS, Major functions of nucleus are the control of cellular, activities and storage of hereditary material. Several, processes are involved in the nuclear functions., Functions of nucleus:, 1. Control of all the cell activities that include metabolism,, protein synthesis, growth and reproduction (cell, division), 2. Synthesis of RNA, 3. Formation of subunits of ribosomes, 4. Sending genetic instruction to the cytoplasm for, protein synthesis through messenger RNA (mRNA)
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14, , Section 1 t General Physiology, , 5. Control of the cell division through genes, 6. Storage of hereditary information (in genes), and transformation of this information from one, generation of the species to the next., , DEOXYRIBONUCLEIC ACID, Deoxyribonucleic acid (DNA) is a nucleic acid that carries, the genetic information to the offspring of an organism., DNA forms the chemical basis of hereditary characters., It contains the instruction for the synthesis of proteins in, the ribosomes. Gene is a part of a DNA molecule., DNA is present in the nucleus (chromosome), and mitochondria of the cell. The DNA present in the, nucleus is responsible for the formation of RNA. RNA, regulates the synthesis of proteins by ribosomes. DNA, in mitochondria is called non-chromosomal DNA., STRUCTURE OF DNA, DNA is a doublestranded complex nucleic acid. It, is formed by deoxyribose, phosphoric acid and four, types of bases. Each DNA molecule consists of two, polynucleotide chains, which are twisted around one, another in the form of a double helix. The two chains are, formed by the sugar deoxyribose and phosphate. These, two substances form the backbone of DNA molecule., Both chains of DNA are connected with each other by, some organic bases (Fig. 1.10)., Each chain of DNA molecule consists of many, nucleotides. Each nucleotide is formed by:, 1. Deoxyribose – sugar, 2. Phosphate, 3. One of the following organic (nitrogenous) bases:, Purines, – Adenine (A), – Guanine (G), Pyrimidines – Thymine (T), – Cytosine (C), The strands of DNA are arranged in such a way that, both are bound by specific pairs of bases. The adenine, of one strand binds specifically with thymine of opposite, strand. Similarly, the cytosine of one strand binds with, guanine of the other strand., DNA forms the component of chromosomes, which, carries the hereditary information. The hereditary information that is encoded in DNA is called genome. Each, DNA molecule is divided into discrete units called, genes., , GENE, Gene is a portion of DNA molecule that contains the, message or code for the synthesis of a specific protein, , from amino acids. It is like a book that contains the, information necessary for protein synthesis. Gene is, considered as the basic hereditary unit of the cell., In the nucleotide of DNA, three of the successive, base pairs are together called a triplet or a codon. Each, codon codes or forms code word (information) for one, amino acid. There are 20 amino acids and there is, separate code for each amino acid. For example, the, triplet CCA is the code for glycine and GGC is the code, for proline., Thus, each gene forms the code word for a particular, protein to be synthesized in ribosome (outside the, nucleus) from amino acids., GENETIC DISORDERS, A genetic disorder is a disorder that occurs because, of the abnormalities in an individual’s genetic material, (genome). Genetic disorders are either hereditary dis, orders or due to defect in genes., Causes of Gene Disorders, Genetic disorders occur due to two causes:, 1. Genetic variation: Presence of a different form of, gene, 2. Genetic mutation: Generally, mutation means an, alteration or a change in nature, form, or quality., Genetic mutation refers to change of the DNA, sequence within a gene or chromosome of an, organism, which results in the creation of a new, character., Classification of Genetic Disorders, Genetic disorders are classified into four types:, 1. Single gene disorders, 2. Multifactorial genetic disorders, 3. Chromosomal disorders, 4. Mitochondrial DNA disorders., 1. Single Gene Disorders, Single gene disorders or Mendelian or monogenic, disorders occur because of variation or mutation in one, single gene. Examples include sickle cell anemia and, Huntington’s disease., 2. Multifactorial Genetic Disorders, Multifactorial genetic disorders or polygenic disorders, are caused by combination of environmental factors and, mutations in multiple genes. Examples are coronary heart, disease, Alzheimer’s disease, arthritis and diabetes.
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Chapter 1 t Cell, , 15, , FIGURE 1.10: Structure of DNA. A. Double helical structure of DNA; B. Magnified view of the components of DNA., A = Adenine, C = Cytocine, G= Guanine, P = Phosphate, S = Sugar, T = Thymine., , 3. Chromosomal Disorders, Chromosomal disorder is a genetic disorder caused, by abnormalities in chromosome. It is also called, chromosomal abnormality, anomaly or aberration. It often, results in genetic disorders which involve physical or, mental abnormalities. Chromosomal disorder is caused, by numerical abnormality or structural abnormality., Chromosomal disorder is classified into two types:, i. Structural abnormality (alteration) of chromosomes, which leads to disorders like chromosome instability, syndromes (group of inherited diseases which, cause malignancies), ii. Numerical abnormality of chromosomes which is of, two types:, a. Monosomy due to absence of one chromosome, from normal diploid number. Example is Turner’s, , syndrome, which is characterized by physical, disabilities, b. Trisomy due to the presence of one extra, chromosome along with normal pair of chromosomes in the cells. Example is Down syndrome,, which is characterized by physical disabilities, and mental retardation., 4. Mitochondrial DNA Disorders, Mitochondrial DNA disorders are the genetic disorders, caused by the mutations in the DNA of mitochondria, (nonchromosomal DNA). Examples are Kearns-Sayre, syndrome (neuromuscular disorder characterized by, myopathy, cardiomyopathy and paralysis of ocular muscles) and Leber’s hereditary optic neuropathy (disease, characterized by degeneration of retina and loss of, vision).
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16, , Section 1 t General Physiology, , RIBONUCLEIC ACID, , TRANSCRIPTION OF GENETIC CODE, , Ribonucleic acid (RNA) is a nucleic acid that contains, a long chain of nucleotide units. It is similar to DNA but, contains ribose instead of deoxyribose. Various functions, coded in the genes are carried out in the cytoplasm of, the cell by RNA. RNA is formed from DNA., , The word transcription means copying. It indicates the, copying of genetic code from DNA to RNA. The proteins, are synthesized in the ribosomes which are present in the, cytoplasm. However, the synthesis of different proteins, depends upon the information (sequence of codon), encoded in the genes of the DNA which is present in the, nucleus. Since DNA is a macromolecule, it cannot pass, through the pores of the nuclear membrane and enter, the cytoplasm. But, the information from DNA must be, sent to ribosome. So, the gene has to be transcribed, (copied) into mRNA which is developed from DNA., Thus, the first stage in the protein synthesis is, transcription of genetic code, which occurs within, the nucleus. It involves the formation of mRNA and, simultaneous copying or transfer of information from, DNA to mRNA. The mRNA enters the cytoplasm from, the nucleus and activates the ribosome resulting in, protein synthesis. The formation of mRNA from DNA is, facilitated by the enzyme RNA polymerase., , STRUCTURE OF RNA, Each RNA molecule consists of a single strand of, polynucleotide unlike the doublestranded DNA. Each, nucleotide in RNA is formed by:, 1. Ribose – sugar., 2. Phosphate., 3. One of the following organic bases:, Purines, – Adenine (A), – Guanine (G), Pyrimidines – Uracil (U), – Cytosine (C)., Uracil replaces the thymine of DNA and it has similar, structure of thymine., TYPES OF RNA, , TRANSLATION OF GENETIC CODE, , Ribosomal RNA is present within the ribosome and forms, a part of the structure of ribosome. It is responsible for the, assembly of protein from amino acids in the ribosome., , Translation is the process by which protein synthesis, occurs in the ribosome of the cell under the direction, of genetic instruction carried by mRNA from DNA. Or, it, is the process by which the mRNA is read by ribosome, to produce a protein. This involves the role of other two, types of RNA, namely tRNA and rRNA., The mRNA moves out of nucleus into the cytoplasm., Now, a group of ribosomes called polysome gets, attached to mRNA. The sequence of codons in mRNA, are exposed and recognized by the complementary, sequence of base in tRNA. The complementary, sequence of base is called anticodon. According to the, sequence of bases in anticodon, different amino acids, are transported from the cytoplasm into the ribosome, by tRNA that acts as a carrier. With the help of rRNA,, the protein molecules are assembled from amino acids., The protein synthesis occurs in the ribosomes which are, attached to rough endoplasmic reticulum., , GENE EXPRESSION, , GROWTH FACTORS, , Gene expression is the process by which the information, (code word) encoded in the gene is converted into, functional gene product or document of instruction, (RNA) that is used for protein synthesis., Gene expression involves two steps:, 1. Transcription., 2. Translation., , Growth factors are proteins which act as cell signaling, molecules like cytokines (Chapter 17) and hormones, (Chapter 65). These factors bind with specific surface, receptors of the target cell and activate proliferation,, differentiation and/or maturation of these cells., Often, the term growth factor is interchangeably used, with the term cytokine. But growth factors are distinct, , RNA is of three types. Each type of RNA plays a specific, role in protein synthesis. The three types of RNA are:, 1. Messenger RNA (mRNA), Messenger RNA carries the genetic code of the amino, acid sequence for synthesis of protein from the DNA to, the cytoplasm., 2. Transfer RNA (tRNA), Transfer RNA is responsible for decoding the genetic, message present in mRNA., 3. Ribosomal RNA (rRNA)
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Chapter 1 t Cell, from cytokines. Growth factors act on the cells of the, growing tissues. But cytokines are concerned with the, cells of immune system and hemopoietic cells., Many growth factors are identified. The known growth, factors are:, 1. Plateletderived growth factor – PDGF (Chapter 18), 2. Colony stimulating factors – CSF (Chapter 16), 3. Nerve growth factors – NGF (Chapter 134), 4. Neurotropins (Chapter 134), 5. Erythropoietin (Chapter 10), 6. Thrombopoietin (Chapter 18), 7. Insulinlike growth factors – IGF (Chapter 66), 8. Epidermal growth factor – present in keratinocytes, and fibroblasts. It inhibits growth of hair follicles and, cancer cells, 9. Basic fibroblast growth factor – present in blood, vessels. It is concerned with the formation of new, blood vessels, 10. Myostatin – present in skeletal muscle fibers. It, controls skeletal muscle growth, 11. Transforming growth factors (TGF) – present in, transforming cells (cells undergoing differentiation), and in large quantities in tumors and cancerous, tissue. TGF is of two types:, i. TGFα secreted in brain, keratinocytes and, macrophages. It is concerned with growth of, epithelial cells and wound healing, ii. TGFβ secreted by hepatic cells, T lymphocytes,, B lymphocytes, macrophages and mast cells., When the liver attains the maximum size in, adults, it controls liver growth by inhibiting proliferation of hepatic cells. TGFβ also causes, immunosuppression., , CELL DEATH, , 17, , Functional Significance of Apoptosis, The purpose of apoptosis is to remove unwanted cells, without causing any stress or damage to the neighboring, cells. The functional significance of apoptosis:, 1. Plays a vital role in cellular homeostasis. About, 10 million cells are produced everyday in human, body by mitosis. An equal number of cells die by, apoptosis. This helps in cellular homeostasis, 2. Useful for removal of a cell that is damaged beyond, repair by a virus or a toxin, 3. An essential event during the development and in, adult stage., Examples:, i. A large number of neurons are produced during, the development of central nervous system., But up to 50% of the neurons are removed by, apoptosis during the formation of synapses, between neurons, ii. Apoptosis is responsible for the removal of, tissues of webs between fingers and toes during, developmental stage in fetus, iii. It is necessary for regression and disappearance, of duct systems during sex differentiation in fetus, (Chapter 74), iv. The cell that looses the contact with neighboring, cells or basal lamina in the epithelial tissue dies, by apoptosis. This is essential for the death of old, enterocytes that shed into the lumen of intestinal, glands (Chapter 41), v. It plays an important role in the cyclic sloughing, of the inner layer of endometrium, resulting in, menstruation (Chapter 80), vi. Apoptosis removes the autoaggressive T cells, and prevents autoimmune diseases., , Cell death occurs by two distinct processes:, 1. Apoptosis, 2. Necrosis., , Activation of Apoptosis, , APOPTOSIS, , Apoptosis is activated by either withdrawal of positive, signals (survival factors) or arrival of negative signals., , Apoptosis is defined as the natural or programed death, of the cell under genetic control. Originally, apoptosis, refers to the process by which the leaves fall from trees, in autumn (In Greek, apoptosis means ‘falling leaves’)., It is also called ‘cell suicide’ since the genes of the cell, play a major role in the death., This type of programmed cell death is a normal, phenomenon and it is essential for normal development, of the body. In contrast to necrosis, apoptosis usually, does not produce inflammatory reactions in the, neighboring tissues., , Withdrawal of positive signals, Positive signals are the signals which are necessary for, the long-time survival of most of the cells. The positive, signals are continuously produced by other cells or, some chemical stimulants. Best examples of chemical, stimulants are:, i. Nerve growth factors (for neurons), ii. Interleukin-2 (for cells like lymphocytes)., The absence or withdrawal of the positive signals, activates apoptosis.
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18, , Section 1 t General Physiology, , Arrival of negative signals, Negative signals are the external or internal stimuli which, initiate apoptosis. The negative signals are produced, during various events like:, 1. Normal developmental procedures, 2. Cellular stress, 3. Increase in the concentration of intracellular oxidants, 4. Viral infection, 5. Damage of DNA, 6. Exposure to agents like chemotherapeutic drugs,, X-rays, ultraviolet rays and the death-receptor, ligands., Death-receptor ligands and death receptors, Deathreceptor ligands are the substances which bind, with specific cell membrane receptors and initiate the, process of apoptosis. The common death-receptor, ligands are tumor necrosis factors (TNF α, TNF β) and, Fas ligand (which binds to the receptor called Fas)., Deathreceptors are the cell membrane receptors, which receive the death-receptor ligands. Well-characterized death receptors are TNF receptor-1 (TNFR1) and, TNF-related apoptosis inducing ligand (TRAIL) receptors, called DR4 and DR5., Role of mitochondria in apoptosis, External or internal stimuli initiate apoptosis by activating, the proteases called caspases (cysteinyl-dependent, aspartatespecific proteases). Normally, caspases are, suppressed by the inhibitor protein called apoptosis, , 4. Nuclear membrane becomes discontinuous and the, DNA inside nucleus is cleaved into small fragments, 5. Following the degradation of DNA, the nucleus, breaks into many discrete nucleosomal units, which, are also called chromatin bodies, 6. Cell membrane breaks and shows bubbled, appearance, 7. Finally, the cell breaks into several fragments, containing intracellular materials including chromatin, bodies and organelles of the cell. Such cellular, fragments are called vesicles or apoptotic bodies, 8. Apoptotic bodies are engulfed by phagocytes and, dendritic cells., Abnormal Apoptosis, Apoptosis within normal limits is beneficial for the body., However, too much or too little apoptosis leads to, abnormal conditions., Common abnormalities due to too much apoptosis:, 1. Ischemicrelated injuries, 2. Autoimmune diseases like:, i. Hemolytic anemia, ii. Thrombocytopenia, iii. Acquired immunodeficiency syndrome (AIDS), 3. Neurodegenerative diseases like Alzheimer’s, disease., Common abnormalities due to too little apoptosis:, , inhibiting factor (AIF)., , When the cells receive the apoptotic stimulus,, mitochondria releases two protein materials. First one is, Cytochrome C and the second protein is called second, mitochondria-derived activator of caspases (SMAC) or, its homologudiablo., SMAC/diablo inactivates AIF so that the inhibitor is, inhibited. During this process, SMAC/diablo and AIF, aggregate to form apoptosome which activates caspases., Cytochrome C also facilitates caspase activation., Apoptotic Process, Cell shows sequence of characteristic morphological, changes during apoptosis, viz.:, 1. Activated caspases digest the proteins of cytoskeleton and the cell shrinks and becomes round, 2. Because of shrinkage, the cell losses the contact, with neighboring cells or surrounding matrix, 3. Chromatin in the nucleus undergoes degradation, and condensation, , 1. Cancer, 2. Autoimmune lymphoproliferative syndrome (ALPS)., NECROSIS, Necrosis (means ‘dead’ in Greek) is the uncontrolled, and unprogramed death of cells due to unexpected and, accidental damage. It is also called ‘cell murder’ because, the cell is killed by extracellular or external events. After, necrosis, the harmful chemical substances released, from the dead cells cause damage and inflammation of, neighboring tissues., Causes for Necrosis, Common causes of necrosis are injury, infection,, inflammation, infarction and cancer. Necrosis is induced, by both physical and chemical events such as heat,, radiation, trauma, hypoxia due to lack of blood flow and, exposure to toxins.
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Chapter 1 t Cell, , 19, , Necrotic Process, , CELL ADAPTATION, , Necrosis results in lethal disruption of cell structure and, activity. The cell undergoes a series of characteristic, changes during necrotic process, viz., 1. Cell swells causing damage of the cell membrane, and appearance of many holes in the membrane, 2. Intracellular contents leak out into the surrounding, environment, 3. Intracellular environment is altered, 4. Simultaneously, large amount of calcium ions are, released by the damaged mitochondria and other, organelles, 5. Presence of calcium ions drastically affects the, organization and activities of proteins in the intracellular components, 6. Calcium ions also induce release of toxic materials, that activate the lysosomal enzymes, 7. Lysosomal enzymes cause degradation of cellular, components and the cell is totally disassembled, resulting in death, 8. Products broken down from the disassembled cell, are ingested by neighboring cells., , Cell adaptation refers to the changes taking place in a, cell in response to environmental changes., Normal functioning of the cell is always threatened by, various factors such as stress, chemical agents, diseases, and environmental hazards. Yet, the cell survives and, continues the function by means of adaptation. Only, during extreme conditions, the cell fails to withstand the, hazardous factors which results in destruction and death, of the cell., Cellular adaptation occurs by any of the following, mechanisms., 1. Atrophy, 2. Hypertrophy, 3. Hyperplasia, 4. Dysplasia, 5. Metaplasia., , Reaction of Neighboring Tissues, after Necrosis, , Causes of Atrophy, , Tissues surrounding the necrotic cells react to the, breakdown products of the dead cells, particularly, the derivatives of membrane phospholipids like the, arachidonic acid. Along with other materials, arachidonic, acid causes the following inflammatory reactions in the, surrounding tissues:, 1. Dilatation of capillaries in the region and thereby, increasing local blood flow, 2. Increase in the temperature leading to reddening of, the tissues, 3. Release of histamine from these tissues which, induces pain in the affected area, 4. Migration of leukocytes and macrophages from, blood to the affected area because of increased, capillary permeability, 5. Movement of water from blood into the tissues, causing local edema, 6. Engulfing and digestion of cellular debris and, foreign materials like bacteria by the leukocytes and, macrophages, 7. Activation of immune system resulting in the removal, of foreign materials, 8. Formation of pus by the dead leukocytes during this, process, 9. Finally, tissue growth in the area and wound healing., , ATROPHY, Atrophy means decrease in size of a cell. Atrophy of more, number of cells results in decreased size or wasting of, the concerned tissue, organ or part of the body., , Atrophy is due to one or more number of causes such, as:, i. Poor nourishment, ii. Decreased blood supply, iii. Lack of workload or exercise, iv. Loss of control by nerves or hormones, v. Intrinsic disease of the tissue or organ., Types of Atrophy, Atrophy is of two types, physiological atrophy and, pathological atrophy. Examples of physiological atrophy, are the atrophy of thymus in childhood and tonsils in, adolescence. The pathological atrophy is common in, skeletal muscle, cardiac muscle, sex organs and brain., HYPERTROPHY, Hypertrophy is the increase in the size of a cell., Hypertrophy of many cells results in enlargement or, overgrowth of an organ or a part of the body. Hypertrophy, is of three types., 1. Physiological Hypertrophy, Physiological hypertrophy is the increase in size due, to increased workload or exercise. The common, physiological hypertrophy includes:
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20, , Section 1 t General Physiology, , i. Muscular hypertrophy: Increase in bulk of, skeletal muscles that occurs in response to, strength training exercise, ii. Ventricular hypertrophy: Increase in size of, ventricular muscles of the heart which is advantageous only if it occurs in response to exercise., , 3. Pathological Hyperplasia, Pathological hyperplasia is the increase in number of, cells due to abnormal increase in hormone secretion., It is also called hormonal hyperplasia. For example, in, gigantism, hypersecretion of growth hormone induces, hyperplasia that results in overgrowth of the body., , 2. Pathological Hypertrophy, , DYSPLASIA, , Increase in cell size in response to pathological changes, is called pathological hypertrophy. Example is the, ventricular hypertrophy that occurs due to pathological, conditions such as high blood pressure, where the, workload of ventricles increases., , Dysplasia is the condition characterized by the abnormal, change in size, shape and organization of the cell., Dysplasia is not considered as true adaptation and it, is suggested as related to hyperplasia. It is common in, epithelial cells of cervix and respiratory tract., , 3. Compensatory Hypertrophy, , METAPLASIA, , Compensatory hypertrophy is the increase in size of the, cells of an organ that occurs in order to compensate, the loss or dysfunction of another organ of same type., Examples are the hypertrophy of one kidney when, the other kidney stops functioning; and the increase, in muscular strength of an arm when the other arm is, dysfunctional or lost., HYPERPLASIA, Hyperplasia is the increase in number of cells due to, increased cell division (mitosis). It is also defined as, abnormal or unusual proliferation (multiplication) of cells, due to constant cell division. Hyperplasia results in gross, enlargement of the organ. Hyperplasia involves constant, cell division of the normal cells only. Hyperplasia is of, three types., 1. Physiological Hyperplasia, Physiological hyperplasia is the momentary adaptive, response to routine physiological changes in the body., For example, during the proliferative phase of each, menstrual cycle, the endometrial cells in uterus increase, in number., 2. Compensatory Hyperplasia, Compensatory hyperplasia is the increase in number of, cells in order to replace the damaged cells of an organ, or the cells removed from the organ., Compensatory hyperplasia helps the tissues and, organs in regeneration. It is common in liver. After, the surgical removal of the damaged part of liver,, there is increase in the number of liver cells resulting, in regeneration. Compensatory hyperplasia is also, common in epithelial cells of intestine and epidermis., , Metaplasia is the condition that involves replacement, of one type of cell with another type of cell. It is of two, types., 1. Physiological Metaplasia, Replacement of cells in normal conditions is called, physiological metaplasia. Examples are transformation, of cartilage into bone and transformation of monocytes, into macrophages., 2. Pathological Metaplasia, Pathological metaplasia is the irreversible replacement, of cells due to constant exposure to harmful stimuli. For, example, chronic smoking results in transformation of, normal mucus secreting ciliated columnar epithelial cells, into non-ciliated squamous epithelial cells, which are, incapable of secreting mucus. These transformed cells, may become cancerous cells if the stimulus (smoking), is prolonged., , CELL DEGENERATION, Cell degeneration is a process characterized by damage, of the cells at cytoplasmic level, without affecting, the nucleus. Degeneration may result in functional, impairment or deterioration of a tissue or an organ. It, is common in metabolically active organ like liver, heart, and kidney. Degenerative changes are reversible in, most of the cells., Causes for Cell Degeneration, Common causes for cell degeneration:, 1. Atrophy, hypertrophy, hyperplasia and/or dysplasia, of cell
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Chapter 1 t Cell, 2. Fluid accumulation in the cell, 3. Fat infiltration into the cell, 4. Calcification of cellular organelles., , CELL AGING, Cell aging is the gradual structural and functional, changes in the cells that occur over the passage of time., It is now suggested that cell aging is due to damage, of cellular substances like DNA, RNA, proteins and, lipids, etc. when the cell becomes old. When more, cellular substances are damaged, the cellular function, decreases. This causes deterioration of tissues, organs, or parts of the body. Finally, the health of the body starts, declining and this leads to death. So, the cell aging, determines the health and life span of the body., , STEM CELLS, Stem cells are the primary cells capable of reforming, themselves through mitotic division and differentiating, into specialized cells. These cells serve as repair, system of the body and are present in all multicellular, organisms., TYPES OF STEM CELLS, Stem cells are of two types:, 1. Embryonic stem cells derived from embryo, 2. Adult stem cells derived from adults., 1. Embryonic Stem Cells, Embryonic stem cells are derived from the inner cell, mass of a blastocyst which is an early stage of embryo., It takes about 4 to 5 days after fertilization to reach, the blastocyst stage and it has about 30 to 50 cells., Embryonic stem cells have two important qualities:, i. Self-renewal capacity, ii. Pluripotent nature, i.e. these cells are capable of, differentiating into all types of cells in ectodermal,, endodermal and mesodermal layers., Because of these two qualities, the embryonic stem, cells can be used therapeutically for regeneration or, replacement of diseased or destroyed tissues. In fact,, embryonic pluripotent stem cells are now cultured and, lot of research is going on to explore the possibility of, using these cells in curing the disorders like diabetes, , 21, , mellitus by cell replacement technique. But, ethical, issues arise because the embryo has to be destroyed to, collect the stem cells., Stem cells from umbilical cord blood, Stem cells in umbilical cord blood are collected from, the placenta or umbilical cord. Use of these stem cells, for research and therapeutic purposes does not create, any ethical issue because it does not endanger the life, of the fetus or newborn. Because of vitality and easy, availability, the umbilical cord blood stem cells are, becoming a potent resource for transplant therapies., Nowadays, these stem cells are used to treat about 70, diseases and are used in many transplants worldwide., 2. Adult Stem Cells, Embryonic stem cells do not disappear after birth. But, remain in the body as adult stem cells and play a role, in repair of damaged tissues. However, their number, becomes less. Adult stem cells are the undifferentiated, multipotent progenitor cells found in growing children, and adults. These are also known as somatic stem cells, and are found everywhere in the body. These cells are, capable of dividing and reforming the dying cells and, regenerating the damaged tissues. So, these stem cells, can also be used for research and therapeutic purposes., Adult stem cells are collected from bone marrow., Two types of stem cells are present in bone marrow:, i. Hemopoietic stem cells, which give rise to blood, cells (Chapter 10), ii. Bone marrow stromal cells, which can differentiate into cardiac and skeletal muscle cells., ADVANTAGES OF STEM CELLS, Adult stem cells from bone marrow are used in bone, marrow transplant to treat leukemia and other blood, disorders since 30 years. Recently, it is known that, these stem cells can develop into nerve cells, liver cells,, skeletal muscle cells and cardiac muscle cells., Recent discoveries also reveal that the stem cells, are present in several tissues which include blood, blood, vessels, skeletal muscle, liver, skin and brain. It is also, found that these cells are capable of differentiating into, multiple cell types. So, the cell-based therapy using, stem cells may be possible to treat many diseases, such as heart diseases, diabetes, Parkinson’s disease,, Alzheimer’s disease, spinal cord injury, stroke and, rheumatoid arthritis.
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Chapter, , Cell Junctions, , 2, , DEFINITION AND CLASSIFICATION, OCCLUDING JUNCTIONS, , , , TIGHT JUNCTION, APPLIED PHYSIOLOGY, , COMMUNICATING JUNCTIONS, , , , , GAP JUNCTION, CHEMICAL SYNAPSE, APPLIED PHYSIOLOGY, , ANCHORING JUNCTIONS, , , , , , , ADHERENS JUNCTION, FOCAL ADHESION, DESMOSOME, HEMIDESMOSOME, APPLIED PHYSIOLOGY, , CELL ADHESION MOLECULES, , , TYPES, , DEFINITION AND CLASSIFICATION, Cell junction is the connection between the neighboring, cells or the contact between the cell and extracellular, matrix. It is also called membrane junction., Cell junctions are classified into three types:, 1. Occluding junctions, 2. Communicating junctions, 3. Anchoring junctions., , OCCLUDING JUNCTIONS, Cell junctions which prevent intercellular exchange of, substances are called occluding junctions, i.e. these, junctions prevent the movement of ions and molecules, from one cell to another cell. Tight junctions belong to, this category., TIGHT JUNCTION, Tight junction is the intercellular occluding junction, that prevents the passage of large molecules. It is also, , called zonula occludens. It is the region where the cell, membranes of the adjacent cells fuse together firmly., This type of junction is present in the apical margins of, epithelial and endothelial cells in intestinal mucosa, wall, of renal tubule, capillary wall and choroid plexus., Structure of Tight Junction, Tight junction is made up of a ridge which has two halves., One half of the ridge is from one cell and another half, is from the other cell. Both halves of the ridge fuse with, each other very tightly and occupy the space between, the two cells (Fig. 2.1). Each half of the ridge consists of, tight junction strands., , Proteins of tight junction, Proteins involved in the formation of tight junctions are, classified into two types:, 1. Tight junction membrane proteins or integral mem, brane proteins, such as occludin, claudin and junc, tional adhesion molecules (JAMs)
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Chapter 2 t Cell Junctions, , 23, , 2. Scaffold (framework or platform) proteins or peri, pheral membrane proteins or cytoplasmic plaque, proteins such as cingulin, symplekin and ZO1, 2, 3., Tight junction membrane protein molecules are, anchored in the strands of the ridge and attach with their, counterparts of neighboring cell, so that both the cells, are held together. The scaffold (platform) proteins are, attached with the tight junction membrane proteins and, strengthen the anchoring in the ridges., , 1. Hereditary deafness, 2. Ichthyosis (scaly skin), 3. Sclerosing cholangitis (inflammation of bile duct, causing obstruction), 4. Hereditary hypomagnesemia (low level of magne, sium in the blood), 5. Synovial sarcoma (soft tissue cancer), Functions of tight junction are affected by some, bacteria and viruses also., , Functions of Tight Junction, , COMMUNICATING JUNCTIONS, , 1. Strength and stability: The tight junction holds the, neighboring cells of the tissues firmly and thus, provides strength and stability to the tissues., 2. Selective permeability (gate function): The tight, junction forms a selective barrier for small molecules, and a total barrier for large molecules., In the epithelial and endothelial cells, tight, junction is the most apical intercellular junction,, which functions as selective (semipermeable) dif, fusion barriers between the neighboring cells. This, function is called barrier or gate function. Barrier, function of tight junction regulates the interchange, of ions, water and varieties of macromolecules, between the cells. The magnitude of this function, varies in different tissues. In some epithelial cells,, few substances pass through the tight junction, (by diffusion or active transport). In other cells, no, substance passes through the tight junction., 3. Fencing function: Tight junction prevents the lateral, movement of proteins (integral membrane proteins), and lipids in cell membrane and thus acts as a, fence. The fencing function maintains the different, composition of proteins and lipids between the, apical and basolateral plasma membrane domains., Because of this function, the tight junction is some, times referred as impermeable junction., 4. Maintenance of cell polarity: Fencing function of, the tight junction maintains the cell polarity by, keeping the proteins in the apical region of the cell, membrane., 5. Blood-brain barrier: Tight junction in the brain capill, aries forms the bloodbrain barrier, which prevents, the entrance of many substances from capillary blood, into brain tissues. Only lipidsoluble substances like, drugs and steroid hormones can pass through the, bloodbrain barrier., , Cell junctions which permit the intercellular exchange, of substances are called communicating junctions,, i.e. these junctions permit the movement of ions and, molecules from one cell to another cell. Gap junction and, chemical synapse are the communicating junctions., GAP JUNCTION, Gap junction is the intercellular junction that allows, passage of ions and smaller molecules between the, cells. It is also called nexus. It is present in heart, basal, part of epithelial cells of intestinal mucosa, etc., Structure of Gap Junction, Membranes of the two adjacent cells lie very close to, each other and the intercellular space is reduced from, the usual size of 2.5 to 3 nm. Cytoplasm of the two cells, is connected by the channels formed by the membranes, of both cells. So, the molecules move from one cell to, another cell directly through these channels, without, having contact with extracellular fluid (ECF)., Each channel consists of two halves. Each half, belongs to one of the two adjacent cells. Each half of the, , APPLIED PHYSIOLOGY, Diseases caused by mutation of genes encoding, proteins of tight junction:, , FIGURE 2.1: Tight junction
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24, , Section 1 t General Physiology, 1. Deafness, 2. Keratoderma (thickening of skin on palms and, soles), 3. Cataract (opacity of lens in eye), 4. Peripheral neuropathy (damage to the nerves of, peripheral nervous system), 5. CharcotMarieTooth disease (a form of neuro, pathy), 6. Heterotaxia (abnormal arrangement of organs or, parts of the body in relation to leftright symmetry)., , ANCHORING JUNCTIONS, FIGURE 2.2: Gap junction, , channel is surrounded by 6 subunits of proteins which, are called connexins or connexons (Fig. 2.2)., Functions of Gap Junction, 1. Diameter of the channel in the gap junction is about, 1.5 to 3 nm. So, the channel permits the passage of, glucose, amino acids, ions and other substances,, which have a molecular weight less than 1,000, 2. It helps in the exchange of chemical messengers, between the cells, 3. It helps in rapid propagation of action potential from, one cell to another cell., Regulation of the Diameter of, Channels in Gap Junction, , Anchoring junctions are the junctions, which provide stren, gth to the cells by acting like mechanical attachments,, i.e. these junctions provide firm structural attachment, between two cells or between a cell and the extracellular, matrix (Fig. 2.3). Anchoring junctions are responsible for, the structural integrity of the tissues and are present, in the tissues like heart muscle and epidermis of skin,, which are subjected to severe mechanical stress., The firm attachment between two cells or between, a cell and the extracellular matrix is provided by either, actin filaments or the intermediate filaments. Depending, upon this, anchoring junctions are classified into four, types:, 1. Actin filament attachment, i. Adherens junction (cell to cell), ii. Focal adhesion (cell to matrix), 2. Intermediate filament attachment, i. Desmosome (cell to cell), ii. Hemidesmosome (cell to matrix), , In the gap junctions, the diameter of each channel is, regulated by the intracellular calcium ions. When the, concentration of intracellular calcium ion increases, the, protein subunits of connexin surrounding the channel, come close to each other by sliding. Thus, the diameter, of the channel decreases. The diameter of the channel, is also regulated by pH, electrical potential, hormones, or neurotransmitter., CHEMICAL SYNAPSE, Chemical synapse is the junction between a nerve fiber, and a muscle fiber or between two nerve fibers, through, which the signals are transmitted by the release of, chemical transmitter (Refer Chapter 140)., APPLIED PHYSIOLOGY, Mutation in the genes encoding the connexins causes, diseases such as:, , FIGURE 2.3: Anchoring junctions
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Chapter 2 t Cell Junctions, ADHERENS JUNCTION, Adherens junction is the cell to cell junction, which, connects the actin filaments of one cell to those of, another cell. In some places like epithelial linings, this, junction forms a continuous adhesion (zonula adherens), just below the tight junctions. In adherens junction, the, membranes of the adjacent cells are held together by, some transmembrane proteins called cadherins., Adherens junction provides strong mechanical, attachments of the adjacent cells. Adherens junction is, present in the intercalated disks between the branches, of cardiac muscles (Chapter 89). During the contractions, and relaxation of heart, the cardiac muscle fibers are, held together tightly by means of this junction. The, adherens junction present in epidermis helps the skin to, withstand the mechanical stress., FOCAL ADHESION, Focal adhesion is the cell to matrix junctions,, which connects the actin filaments of the cell to the, extracellular matrix. In epithelia of various organs, this, junction connects the cells with their basal lamina. The, transmembrane proteins, which hold the cell membrane, and the matrix are called integrins., DESMOSOME, Desmosome is a cell to cell junction, where the inter, mediate filaments connect two adjacent cells. Desmo, , 25, , some is also called macula adherens. The membranes, of two adjacent cells, which oppose each other, are, thickened and become spotlike patches. Intermediate, filaments are attached with the thickened patches. Some, of these filaments are parallel to the membrane and, others are arranged in radiating fashion. Desmosomes, function like tight junctions. The transmembrane proteins, involved in desmosome are mainly cadherins., HEMIDESMOSOME, Hemidesmosome is a cell to matrix junction, which, connects the intermediate filaments of the cell to the, extracellular matrix. This type of cell junction is like half, desmosome and the thickening of membrane of only, one cell occurs. So, this is known as hemidesmosome, or half desmosome. Mostly, the hemidesmosome, connects the cells with their basal lamina. The proteins, involved in this are integrins (Table 2.1)., APPLIED PHYSIOLOGY, 1. Dysfunction of adherens junction and focal junction, in colon due to mutation of proteins results in colon, cancer. It also leads to tumor metastasis (spread of, cancer cells from a primary tumor to other parts of, the body), 2. Dysfunction of desmosome causes bullous pem, phigoid (autoimmune disease with tense blistering, , TABLE 2.1: Cell junctions, Junction type, , Proteins involved, , Function, , Example, , Tight junction, , Occludin, Claudin, JAMs, Cingulin, Symplekin, ZO1, 2, 3, , Strength and stability to tissues, Selective permeability, Fencing function, Maintenance of cell polarity, Formation of bloodbrain barrier, , Epithelial lining of intestinal mucosa, and renal tubule, Endothelium in capillary wall and, choroid plexus, , Gap junction, , Connexins, , Allows passage of small molecules, ions, and chemical messengers, Propagation of action potential, , Epithelial lining, Heart, Intestine, , Adherens junction, , Cadherins, , Cell to cell attachment, , Epithelial lining, Heart, Epidermis, , Integrins, , Cell attachment to, Basal lamina, Extracellular matrix, , Epithelial lining, , Desmosome, , Cadherins, , Cell to cell attachment, , Epithelial lining, Skin, , Hemidesmosome, , Integrins, , Cell attachment to, Basal lamina, Extracellular matrix, , Epithelial lining, , Focal adhesions
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26, , Section 1 t General Physiology, , eruptions of the skin). The patients with this disease, develop antibodies against cadherins, 3. Dysfunction of hemidesmosome also causes bullous, pemphigoid. The patients develop antibodies, against integrins., , CELL ADHESION MOLECULES, Cell adhesion molecules (CAMs) or cell adhesion, proteins are the protein molecules, which are respons, ible for the attachment of cells to their neighbors or, to basal lamina (or basal membrane). CAMs form the, important structures of intercellular connections and are, responsible for structural organization of tissues., , TYPES OF CELL ADHESION MOLECULES, Cell adhesion molecules are classified into four types:, 1. Cadherins, which form the molecular limbs between, neighboring cells. These CAMs form adherens, junction and desomosome, 2. Integrins, which form the focal adhesion and, hemidesmosome, 3. IgG super family, which form the cell adhesion, molecules in nervous system, 4. Selectins, which act as receptors for carbohydrates, (ligand or mucin) and are found in platelets and, endothelial cells.
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Transport through, Cell Membrane, , , , , , , , , , Chapter, , 3, , INTRODUCTION, BASIC MECHANISM OF TRANSPORT, PASSIVE TRANSPORT, SPECIAL TYPES OF PASSIVE TRANSPORT, ACTIVE TRANSPORT, SPECIAL TYPES OF ACTIVE TRANSPORT, MOLECULAR MOTORS, APPLIED PHYSIOLOGY, , INTRODUCTION, All the cells in the body must be supplied with essential, substances like nutrients, water, electrolytes, etc. Cells, also must get rid of many unwanted substances like, waste materials, carbon dioxide, etc. The cells achieve, these by means of transport mechanisms across the, cell membrane., Structure of the cell membrane is well suited for the, transport of substances in and out of the cell. Lipids and, proteins of cell membrane play an important role in the, transport of various substances between extracellular, fluid (ECF) and intracellular fluid (ICF). Refer Chapter 1, for details of lipids and proteins of the cell membrane., , BASIC MECHANISM OF TRANSPORT, Two types of basic mechanisms are involved in the, transport of substances across the cell membrane:, 1. Passive transport mechanism, 2. Active transport mechanism., , PASSIVE TRANSPORT, Passive transport is the transport of substances along, the concentration gradient or electrical gradient or, both (electrochemical gradient). It is also known as, diffusion or downhill movement. It does not need, energy. Passive transport is like swimming in the, direction of water flow in a river. Here, the substances, , move from region of higher concentration to the region, of lower concentration. Diffusion is of two types, namely, simple diffusion and facilitated diffusion., Simple diffusion of substances occurs either, through lipid layer or protein layer of the cell membrane., Facilitated diffusion occurs with the help of the carrier, proteins of the cell membrane. Thus, the diffusion can, be discussed under three headings:, 1. Simple diffusion through lipid layer, 2. Simple diffusion through protein layer, 3. Facilitated or carrier-mediated diffusion., SIMPLE DIFFUSION THROUGH LIPID LAYER, Lipid layer of the cell membrane is permeable only to, lipid-soluble substances like oxygen, carbon dioxide and, alcohol. The diffusion through the lipid layer is directly, proportional to the solubility of the substances in lipids, (Fig. 3.1A)., SIMPLE DIFFUSION THROUGH PROTEIN LAYER, Protein layer of the cell membrane is permeable to, water-soluble substances. Mainly, electrolytes diffuse, through the protein layer., Protein Channels or Ion Channels, Throughout the central lipid layer of the cell membrane,, there are some pores. Integral protein molecules of
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28, , Section 1 t General Physiology, , protein layer invaginate into these pores from either, surface of the cell membrane. Thus, the pores present in, the central lipid layer are entirely lined up by the integral, protein molecules. These pores are the hypothetical, pores and form the channels for the diffusion of water,, electrolytes and other substances, which cannot pass, through the lipid layer. As the channels are lined by, protein molecules, these are called protein channels, for water-soluble substances., Types of Protein Channels or Ion Channels, Characteristic feature of the protein channels is the, selective permeability. That is, each channel can permit, only one type of ion to pass through it. Accordingly, the, channels are named after the ions which diffuse through, these channels such as sodium channels, potassium, channels, etc., Regulation of the Channels, Some of the protein channels are continuously opened and most of the channels are always closed. Continuously opened channels are called ungated channels, (Fig. 3.1B). Closed channels are called gated channels., These channels are opened only when required (Fig., 3.1C)., , i. Voltage-gated channels, Voltage-gated channels are the channels which open, whenever there is a change in the electrical potential., For example, in the neuromuscular junction, when action, potential reaches axon terminal, the calcium channels, are opened and calcium ions diffuse into the interior of, the axon terminal from ECF (Chapter 32)., Similarly, in the muscle during the excitation-contraction coupling, the action potential spreads through, the transverse tubules of the sarcotubular system. When, the action potential reaches the cisternae, large number, of calcium ions diffuse from cisternae into sarcoplasm., ii. Ligand-gated channels, Ligand-gated channels are the type of channels which, open in the presence of some hormonal substances., The hormonal substances are called ligands and the, channels are called ligand-gated channels. During the, transmission of impulse through the neuromuscular, junction, acetylcholine is released from the vesicles., The acetylcholine moves through the presynaptic, membrane (membrane of the axon terminal) and, reaches the synaptic cleft. Then, the acetylcholine, molecules cause opening of sodium channels in the, postsynaptic membrane and sodium ions diffuse into, the neuromuscular junction from ECF., , Gated Channels, , iii. Mechanically gated channels, , Gated channels are divided into three categories:, i. Voltage-gated channels, ii. Ligand-gated channels, iii. Mechanically gated channels., , Mechanically gated channels are the channels which, are opened by some mechanical factors. Examples are,, channels present in the pressure receptors (Pacinian, corpuscles) and the receptor cells (hair cells) of organ, , FIGURE 3.1: Hypothetical diagram of simple diffusion through the cell membrane., A. Diffusion through lipid layer; B. Diffusion through ungated channel; C. Diffusion through gated channel.
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Chapter 3 t Transport through Cell Membrane, , 29, , of Corti and vestibular apparatus. When a Pacinian, corpuscle is subjected to pressure, it is compressed, resulting in deformation of its core fiber. This deformation, causes opening of sodium channel and development of, receptor potential (Chapter 139)., Sound waves cause the movement of cilia of hair, cells in organ of Corti (cochlea), which is the receptor, organ in the ear. Movements of the cilia cause opening, of potassium channels leading to the development of, receptor potential (Chapter 174). Similar mechanism, prevails in hair cells of vestibular apparatus also, (Chapter 158)., Ion Channel Diseases, Refer applied physiology of this chapter., FACILITATED OR CARRIERMEDIATED DIFFUSION, Facilitated or carrier-mediated diffusion is the type, of diffusion by which the water-soluble substances, having larger molecules are transported through the, cell membrane with the help of a carrier protein. By this, process, the substances are transported across the cell, membrane faster than the transport by simple diffusion., Glucose and amino acids are transported by, facilitated diffusion. Glucose or amino acid molecules, cannot diffuse through the channels because the, diameter of these molecules is larger than the diameter, of the channels. Molecule of these substances binds, with carrier protein. Now, some conformational change, occurs in the carrier protein. Due to this change, the, molecule reaches the other side of the cell membrane, (Fig. 3.2)., FACTORS AFFECTING RATE OF DIFFUSION, Rate of diffusion of substances through the cell membrane is affected by the following factors:, 1. Permeability of the Cell Membrane, Rate of diffusion is directly proportional to the permeability, of cell membrane. Since the cell membrane is selectively, permeable, only limited number of substances can, diffuse through the membrane., 2. Temperature, Rate of diffusion is directly proportional to the body, temperature. Increase in temperature increases the, rate of diffusion. This is because of the thermal motion, of molecules during increased temperature., , FIGURE 3.2: Hypothetical diagram of facilitated diffusion from, higher concentration (ECF) to lower concentration (ICF)., Stage 1. Glucose binds with carrier protein. Stage 2. Conformational change occurs in the carrier protein and glucose is, released into ICF., , 3. Concentration Gradient or Electrical Gradient, of the Substance across the Cell Membrane, Rate of diffusion is directly proportional to the concentration gradient or electrical gradient of the diffusing, substances across the cell membrane. However,, facilitated diffusion has some limitation beyond certain, level of concentration gradient., 4. Solubility of the Substance, Diffusion rate is directly proportional to the solubility of, substances, particularly the lipid-soluble substances., Since oxygen is highly soluble in lipids, it diffuses very, rapidly through the lipid layer., 5. Thickness of the Cell Membrane, Rate of diffusion is inversely proportional to the thickness, of the cell membrane. If the cell membrane is thick,, diffusion of the substances is very slow., 6. Size of the Molecules, Rate of diffusion is inversely proportional to the size, of the molecules. Thus, the substances with smaller, molecules diffuse rapidly than the substances with, larger molecules., 7. Size of the Ions, Generally, rate of diffusion is inversely proportional to, the size of the ions. Smaller ions can pass through the
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30, , Section 1 t General Physiology, , membrane more easily than larger ions with the same, charge. However, it is not applicable always. For instance,, sodium ions are smaller in size than potassium ions., Still, sodium ions cannot pass through the membrane as, easily as potassium ions because sodium ions have got, the tendency to gather water molecules around them., This makes it difficult for sodium ions to diffuse through, the membrane., , concentration of a solute, through a semipermeable, membrane (Fig. 3.3). The semipermeable membrane, permits the passage of only water or other solvents but, not the solutes., Osmosis can occur whenever there is a difference in, the solute concentration on either side of the membrane., Osmosis depends upon osmotic pressure., Osmotic Pressure, , 8. Charge of the Ions, Rate of diffusion is inversely proportional to the charge, of the ions. Greater the charge of the ions, lesser is the, rate of diffusion. For example, diffusion of calcium (Ca++), ions is slower than the sodium (Na+) ions., , SPECIAL TYPES OF PASSIVE TRANSPORT, In addition to diffusion, there are some special types of, passive transport, viz., 1. Bulk flow, 2. Filtration, 3. Osmosis., BULK FLOW, Bulk flow is the diffusion of large quantity of substances, from a region of high pressure to the region of low, pressure. It is due to the pressure gradient of the, substance across the cell membrane., Best example for bulk flow is the exchange of gases, across the respiratory membrane in lungs. Partial pressure of oxygen is greater in the alveolar air than in the, alveolar capillary blood. So, oxygen moves from alveolar, air into the blood through the respiratory membrane., Partial pressure of carbon dioxide is more in blood than, in the alveoli. So, it moves from the blood into the alveoli, through the respiratory membrane (Chapter 124)., , Osmotic pressure is the pressure created by the solutes, in a fluid. During osmosis, when water or any other, solvent moves from the area of lower concentration to, the area of higher concentration, the solutes in the area, of higher concentration get dissolved in the solvent. This, creates a pressure which is known as osmotic pressure., Normally, the osmotic pressure prevents further, movement of water or other solvent during osmosis., Reverse Osmotic Pressure, Reverse osmosis is a process in which water or other, solvent flows in reverse direction (from the area of, higher concentration to the area of lower concentration, of the solute), if an external pressure is applied on the, area of higher concentration., Colloidal Osmotic Pressure and Oncotic Pressure, The osmotic pressure exerted by the colloidal substances, in the body is called the colloidal osmotic pressure. And,, the osmotic pressure exerted by the colloidal substances, , FILTRATION, Movement of water and solutes from an area of high, hydrostatic pressure to an area of low hydrostatic, pressure is called filtration. Hydrostatic pressure is, developed by the weight of the fluid. Filtration process is, seen at arterial end of the capillaries, where movement, of fluid occurs along with dissolved substances from, blood into the interstitial fluid (Chapter 27). It also occurs, in glomeruli of kidneys (Chapter 52)., OSMOSIS, Osmosis is the special type of diffusion. It is defined, as the movement of water or any other solvent from, an area of lower concentration to an area of higher, , FIGURE 3.3: Osmosis. Red objects = solute, Yellow shade, = water, Green dotted line = semipermeable membrane. In, (I), concentration of solute is high in compartment B and, low in compartment A. So, water moves from A to B through, semipermeable membrane. In (II), entrance of water into B, exerts osmotic pressure.
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Chapter 3 t Transport through Cell Membrane, (proteins) of the plasma is known as oncotic pressure, and it is about 25 mm Hg., Types of Osmosis, Osmosis across the cell membrane is of two types:, 1. Endosmosis: Movement of water into the cell, 2. Exosmosis: Movement of water out of the cell., , ACTIVE TRANSPORT, Active transport is the movement of substances against, the chemical or electrical or electrochemical gradient., It is like swimming against the water tide in a river. It is, also called uphill transport. Active transport requires, energy, which is obtained mainly by breakdown of, high energy compounds like adenosine triphosphate, (ATP)., Active Transport vs Facilitated Diffusion, Active transport mechanism is different from facilitated, diffusion by two ways:, 1. Carrier protein of active transport needs energy,, whereas the carrier protein of facilitated diffusion, does not need energy, 2. In active transport, the substances are transported, against the concentration or electrical or electrochemical gradient. In facilitated diffusion, the substances are transported along the concentration or, electrical or electrochemical gradient., CARRIER PROTEINS OF ACTIVE TRANSPORT, Carrier proteins involved in active transport are of two, types:, 1. Uniport, 2. Symport or antiport., 1. Uniport, Carrier protein that carries only one substance in a, single direction is called uniport. It is also known as, uniport pump., , 2. Symport or Antiport, Symport or antiport is the carrier protein that transports, two substances at a time., Carrier protein that transports two different, substances in the same direction is called symport, or symport pump. Carrier protein that transports two, different substances in opposite directions is called, antiport or antiport pump., , 31, , MECHANISM OF ACTIVE TRANSPORT, When a substance to be transported across the cell, membrane comes near the cell, it combines with, the carrier protein of the cell membrane and forms, substance-protein complex. This complex moves, towards the inner surface of the cell membrane. Now,, the substance is released from the carrier proteins. The, same carrier protein moves back to the outer surface of, the cell membrane to transport another molecule of the, substance., SUBSTANCES TRANSPORTED BY, ACTIVE TRANSPORT, Substances, which are transported actively, are in ionic, form and non-ionic form. Substances in ionic form are, sodium, potassium, calcium, hydrogen, chloride and, iodide. Substances in non-ionic form are glucose, amino, acids and urea., TYPES OF ACTIVE TRANSPORT, Active transport is of two types:, 1. Primary active transport, 2. Secondary active transport., PRIMARY ACTIVE TRANSPORT, Primary active transport is the type of transport, mechanism in which the energy is liberated directly from, the breakdown of ATP. By this method, the substances, like sodium, potassium, calcium, hydrogen and chloride, are transported across the cell membrane., Primary Active Transport of Sodium and, Potassium: Sodium-Potassium Pump, Sodium and potassium ions are transported across the, cell membrane by means of a common carrier protein, called sodium-potassium (Na+-K+) pump. It is also called, Na+-K+ ATPase pump or Na+-K+ ATPase. This pump, transports sodium from inside to outside the cell and, potassium from outside to inside the cell. This pump is, present in all the cells of the body., Na+-K+ pump is responsible for the distribution of, sodium and potassium ions across the cell membrane, and the development of resting membrane potential., Structure of Na+-K+ pump, Carrier protein that constitutes Na+-K+ pump is made, up of two protein subunit molecules, an α-subunit with, a molecular weight of 100,000 and a β-subunit with a, molecular weight of 55,000. Transport of Na+ and K+
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32, , Section 1 t General Physiology, , occurs only by α-subunit. The β-subunit is a glycoprotein, the function of which is not clear., α-subunit of the Na+-K+ pump has got six sites:, i. Three receptor sites for sodium ions on the, inner (towards cytoplasm) surface of the protein, molecule, ii. Two receptor sites for potassium ions on the, outer (towards ECF) surface of the protein, molecule, iii. One site for enzyme adenosine triphosphatase, (ATPase), which is near the sites for sodium., Mechanism of action of Na+-K+ pump, Three sodium ions from the cell get attached to the, receptor sites of sodium ions on the inner surface of the, carrier protein. Two potassium ions outside the cell bind, to the receptor sites of potassium ions located on the, outer surface of the carrier protein (Fig. 3.4, Stage 1)., Binding of sodium and potassium ions to carrier, protein activates the enzyme ATPase. ATPase causes, breakdown of ATP into adenosine diphosphate (ADP), with the release of one high energy phosphate. Now,, the energy liberated causes some sort of conformational, change in the molecule of the carrier protein. Because, of this, the outer surface of the molecule (with potassium, ions) now faces the inner side of the cell. And, the inner, surface of the protein molecule (with sodium ions), faces the outer side of the cell (Fig. 3.4, Stage 2). Now,, dissociation and release of the ions take place so that, the sodium ions are released outside the cell (ECF) and, the potassium ions are released inside the cell (ICF)., Exact mechanisms involved in the dissociation and, release of ions are not yet known., Electrogenic activity of Na+-K+ pump, Na+-K+ pump moves three sodium ions outside the cell, and two potassium ions inside cell. Thus, when the, pump works once, there is a net loss of one positively, charged ion from the cell. Continuous activity of the, sodium-potassium pumps causes reduction in the, number of positively charged ions inside the cell leading, to increase in the negativity inside the cell. This is called, the electrogenic activity of Na+-K+ pump., +, , +, , Abnormalities of Na -K Pump, Refer applied physiology of this Chapter., Transport of Calcium Ions, Calcium is actively transported from inside to outside, the cell by calcium pump. Calcium pump is operated by, a separate carrier protein. Energy is obtained from ATP, , FIGURE 3.4: Hypothetical diagram of sodium-potassium, pump. C = carrier protein. Stage 1: Three Na+ from ICF and, two K+ from ECF bind with ‘C’. Stage 2: Conformational, change occurs in ‘C’ followed by release of Na+ into ECF and, K+ into ICF, , by the catalytic activity of ATPase. Calcium pumps, are also present in some organelles of the cell such, as sarcoplasmic reticulum in the muscle and the, mitochondria of all the cells. These pumps move calcium, into the organelles., Transport of Hydrogen Ions, Hydrogen ion is actively transported across the cell, membrane by the carrier protein called hydrogen pump., It also obtains energy from ATP by the activity of ATPase., The hydrogen pumps that are present in two important, organs have some functional significance., 1. Stomach: Hydrogen pumps in parietal cells of the, gastric glands are involved in the formation of, hydrochloric acid (Chapter 38), 2. Kidney: Hydrogen pumps in epithelial cells of distal, convoluted tubules and collecting ducts are involved, in the secretion of hydrogen ions from blood into, urine (Chapter 54)., SECONDARY ACTIVE TRANSPORT, Secondary active transport is the transport of a substance with sodium ion, by means of a common carrier, protein. When sodium is transported by a carrier protein,, another substance is also transported by the same, protein simultaneously, either in the same direction (of, sodium movement) or in the opposite direction. Thus,, the transport of sodium is coupled with transport of, another substance.
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Chapter 3 t Transport through Cell Membrane, , 33, , Secondary active transport is of two types:, 1. Cotransport, 2. Counter transport., Sodium Cotransport, Sodium cotransport is the process in which, along with, sodium, another substance is transported by a carrier, protein called symport. Energy for movement of sodium, is obtained by breakdown of ATP. And the energy, released by the movement of sodium is utilized for, movement of another substance., Substances carried by sodium cotransport are, glucose, amino acids, chloride, iodine, iron and urate., Carrier protein for sodium cotransport, Carrier protein for the sodium cotransport has two, receptor sites on the outer surface., Among the two sites, one is for binding of sodium, and another site is for binding of other substance., Sodium cotransport of glucose, One sodium ion and one glucose molecule from the, ECF bind with the respective receptor sites of carrier, protein of the cell membrane. Now, the carrier protein, is activated. It causes conformational changes in the, carrier protein, so that sodium and glucose are released, into the cell (Fig. 3.5)., Sodium cotransport of glucose occurs during, absorption of glucose from the intestine and reabsorption, of glucose from the renal tubule., Sodium cotransport of amino acids, Carrier proteins for the transport of amino acids are, different from the carrier proteins for the transport of, glucose. For the transport of amino acids, there are, five sets of carrier proteins in the cell membrane. Each, one carries different amino acids depending upon the, molecular weight of the amino acids., Sodium cotransport of amino acids also occurs, during the absorption of amino acids from the intestine, and reabsorption from renal tubule., Sodium Counter Transport, Sodium counter transport is the process by which the, substances are transported across the cell membrane in, exchange for sodium ions by carrier protein called antiport., Various counter transport systems are:, i. Sodium-calcium counter transport: In this,, sodium and calcium ions move in opposite, directions with the help of a carrier protein. This, type of transport of sodium and calcium ions is, present in all the cells, , FIGURE 3.5: Sodium cotransport. A. Na+ and glucose from, ECF bind with carrier protein; B. Conformational change, occurs in the carrier protein; C. Na+ and glucose are released, into ICF., , ii. Sodium-hydrogen counter transport: In this, system, the hydrogen ions are exchanged for, sodium ions and this occurs in the renal tubular, cells. The sodium ions move from tubular lumen, into the tubular cells and the hydrogen ions, move from tubular cell into the lumen (Figs 3.6, and 3.7), iii. Other counter transport systems: Other counter, transport systems are sodium-magnesium, counter transport, sodium-potassium counter, transport, calcium-magnesium counter transport,, calcium-potassium counter transport, chloridebicarbonate counter transport and chloridesulfate counter transport., , SPECIAL TYPES OF ACTIVE TRANSPORT, In addition to primary and secondary active transport, systems, there are some special categories of active, transport which are generally called the vesicular, transport., Special categories of active transport:, 1. Endocytosis, 2. Exocytosis, 3. Transcytosis., ENDOCYTOSIS, Endocytosis is defined as a transport mechanism, by which the macromolecules enter the cell. Macromolecules (substances with larger molecules) cannot, pass through the cell membrane either by active or by, passive transport mechanism. Such substances are, transported into the cell by endocytosis.
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34, , Section 1 t General Physiology, , FIGURE 3.6: Sodium counter transport. A. Na+ from ECF, and H+ from ICF bind with carrier protein; B. Conformational, change occurs in the carrier protein; C. Na+ enters ICF and H+, enters ECF., , i. Macromolecules (in the form of droplets of fluid), bind to the outer surface of the cell membrane, ii. Now, the cell membrane evaginates around the, droplets, iii. Droplets are engulfed by the membrane, iv. Engulfed droplets are converted into vesicles, and vacuoles, which are called endosomes (Fig., 3.8), v. Endosome travels into the interior of the cell, vi. Primary lysosome in the cytoplasm fuses with, endosome and forms secondary lysosome, vii. Now, hydrolytic enzymes present in the, secondary lysosome are activated resulting in, digestion and degradation of the endosomal, contents., 2. Phagocytosis, Phagocytosis is the process by which particles larger, than the macromolecules are engulfed into the cells., It is also called cell eating. Larger bacteria, larger, antigens and other larger foreign bodies are taken, inside the cell by means of phagocytosis. Only few cells, in the body like neutrophils, monocytes and the tissue, macrophages show phagocytosis. Among these cells,, the macrophages are the largest phagocytic cells., Mechanism of phagocytosis, , FIGURE 3.7: Sodium cotransport and counter transport, by carrier proteins, , Endocytosis is of three types:, 1. Pinocytosis, 2. Phagocytosis, 3. Receptor-mediated endocytosis., , i. When bacteria or foreign body enters the body,, first the phagocytic cell sends cytoplasmic, extension (pseudopodium) around bacteria or, foreign body, ii. Then, these particles are engulfed and, are converted into endosome like vacuole., Vacuole is very large and it is usually called the, phagosome, iii. Phagosome travels into the interior of cell, iv. Primary lysosome fuses with this phagosome, and forms secondary lysosome, v. Hydrolytic enzymes present in the secondary, lysosome are activated resulting in digestion, and degradation of the phagosomal contents, (Fig. 3.9)., , 1. Pinocytosis, Pinocytosis is a process by which macromolecules, like bacteria and antigens are taken into the cells. It is, otherwise called the cell drinking., Mechanism of pinocytosis, Pinocytosis involves following events:, , FIGURE 3.8: Process of pinocytosis
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Chapter 3 t Transport through Cell Membrane, , FIGURE 3.9: Process of phagocytosis, , 3. Receptor-mediated Endocytosis, Receptor-mediated endocytosis is the transport of, macromolecules with the help of a receptor protein., Surface of cell membrane has some pits which contain a, receptor protein called clathrin. Together with a receptor, protein (clathrin), each pit is called receptor-coated pit., These receptor-coated pits are involved in the receptormediated endocytosis (Fig. 3.10)., Mechanism of receptor-mediated endocytosis, i. Receptor-mediated endocytosis is induced by, substances like ligands (Fig. 3.10-i), ii. Ligand molecules approach the cell and bind, to receptors in the coated pits and form ligandreceptor complex (Fig. 3.10-ii), iii. Ligand-receptor complex gets aggregated in the, coated pits. Then, the pit is detached from cell, membrane and becomes the coated vesicle., This coated vesicle forms the endosome (Fig., 3.10-iii), iv. Endosome travels into the interior of the cell., Primary lysosome in the cytoplasm fuses with, endosome and forms secondary lysosome (Fig., 3.10-iv), , 35, , v. Now, the hydrolytic enzymes present in secondary lysosome are activated resulting in release, of ligands into the cytoplasm (Fig. 3.10-v), vi. Receptor may move to a new pit of the cell, membrane (Fig. 3.10-vi)., Receptor-mediated endocytosis play an important, role in the transport of several types of macromolecules, into the cells, viz., i. Hormones: Growth hormone, thyroid stimulating, hormone, luteinizing hormone, prolactin, insulin,, glucagon, calcitonin and catecholamines, ii. Lipids: Cholesterol and low-density lipoproteins, (LDL), iii. Growth factors (GF): Nerve GF, epidermal GF,, platelet-derived GF, interferon, iv. Toxins and bacteria: Cholera toxin, diphtheria, toxin,, pseudomonas, toxin,, recin, and, concanavalin A, v. Viruses: Rous sarcoma virus, semliki forest, virus, vesicular stomatitis virus and adenovirus, vi. Transport, proteins:, Transferrin, and, transcobalamine, vii. Antibodies: IgE, polymeric IgG and maternal, IgG., Some of the receptor-coated pits in cell membrane, are coated with another protein called caveolin instead, of clathrin. Caveolin-coated pits are concerned with the, transport of vitamins into the cell., EXOCYTOSIS, Exocytosis is the process by which the substances are, expelled from the cell. In this process, the substances, are extruded from cell without passing through the cell, membrane. This is the reverse of endocytosis., , FIGURE 3.10: Mechanism of receptor-mediated endocytosis. The numbering of each figure, corresponds with the numbers used in the text.
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36, , Section 1 t General Physiology, the capillary. Many pathogens like human immunodeficiency virus (HIV) are also transported by this mechanism., , MOLECULAR MOTORS, Molecular motors are the protein-based molecular, machines that perform intracellular movements in, response to specific stimuli., FUNCTIONS OF MOLECULAR MOTORS, FIGURE 3.11: Process of exocytosis, , Mechanism of Exocytosis, Exocytosis is involved in the release of secretory, substances from cells. Secretory substances of the, cell are stored in the form of secretory vesicles in the, cytoplasm. When required, the vesicles approach the, cell membrane and get fused with the cell membrane., Later, the contents of the vesicles are released out of, the cell (Fig. 3.11)., Role of Calcium in Exocytosis, Calcium ions play an important role during the release of, some secretory substances such as neurotransmitters., The calcium ions enter the cell and cause exocytosis., However, the exact mechanism of exocytosis is not clear., TRANSCYTOSIS, Transcytosis is a transport mechanism in which an, extracellular macromolecule enters through one side of, a cell, migrates across cytoplasm of the cell and exits, through the other side., Mechanism of Transcytosis, Cell encloses the extracellular substance by invagination, of the cell membrane to form a vesicle. Vesicle then, moves across the cell and thrown out through opposite, cell membrane by means of exocytosis. Transcytosis, involves the receptor-coated pits as in receptor-mediated, endocytosis. Receptor protein coating the pits in this, process is caveolin and not clathrin. Transcytosis is also, called, vesicle trafficking or cytopempsis., Transcytosis plays an important role in selectively, transporting the substances between two environments, across the cells without any distinct change in the, composition of these environments. Example of this type, of transport is the movement of proteins from capillary, blood into interstitial fluid across the endothelial cells of, , 1. Transport of synaptic vesicles containing neurotransmitters from the nerve cell body to synaptic, terminal, 2. Role in cell division (mitosis and meiosis) by pulling, the chromosomes, 3. Transport of viruses and toxins to the interior of the, cell for its own detriment., TYPES OF MOLECULAR MOTORS, Molecular motors are classified into three super, families:, 1. Kinesin, 2. Dynein, 3. Myosin., 1. Kinesin, Kinesin transports substances by moving over the, microtubules. Each kinesin molecule has two heads and, a tail portion. One of the heads hydrolyses ATP to obtain, energy. By utilizing this energy, the other head swings, continuously causing movement of the whole kinesin, molecule (Fig. 3.12). End portion of the tail carries, the cargo (substances to be transported). Kinesin is, responsible for anterograde transport (transport of, substances towards the positive end of microtubule)., 2. Dynein, Dynein is almost similar to kinesin and transports, substances by moving over the microtubules. But it, is responsible for retrograde transport (transport of, substances towards the negative end of microtubule)., 3. Myosin, Myosin transports substances by moving over microfilaments. Myosins are classified into 18 types according, to the amino acid sequence. However, myosin II and, V are functionally significant. Myosin II is involved in, muscle contraction (Chapter 31). Myosin V is involved, in transport of vesicles.
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Chapter 3 t Transport through Cell Membrane, , 37, , APPLIED PHYSIOLOGY, ABNORMALITIES OF SODIUMPOTASSIUM PUMP, Abnormalities in the number or function of Na+-K+ pump, are associated with several pathological conditions., Important examples are:, 1. Reduction in either the number or concentration, of Na+-K+ pump in myocardium is associated with, cardiac failure, 2. Excess reabsorption of sodium in renal tubules is, associated with hypertension., , FIGURE 3.12: Kinesin and dynein motor molecules, , 2. Potassium Channel Diseases, , CHANNELOPATHIES OR ION, CHANNEL DISEASES, , Potassium channel dysfunction causes disorders of, heart, inherited deafness and epileptic seizures in, newborn., , Channelopathies or ion channel diseases are caused, by mutations in genes that encode the ion channels., , 3. Chloride Channel Diseases, , 1. Sodium Channel Diseases, Dysfunction of sodium channels leads to muscle spasm, and Liddle’s syndrome (dysfunction of sodium channels, in kidney resulting in increased osmotic pressure in the, blood and hypertension)., , Dysfunction of chloride channels results in formation, of renal stones and cystic fibrosis. Cystic fibrosis is, a generalized disorder affecting the functions of many, organs such as lungs (due to excessive mucus),, exocrine glands like pancreas, biliary system and, immune system.
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Homeostasis, , , , , , Chapter, , 4, , INTRODUCTION, ROLE OF VARIOUS SYSTEMS OF THE BODY IN HOMEOSTASIS, COMPONENTS OF HOMEOSTATIC SYSTEM, MECHANISM OF ACTION OF HOMEOSTATIC SYSTEM, , , , , NEGATIVE FEEDBACK, POSITIVE FEEDBACK, , INTRODUCTION, ‘Homeostasis’ refers to the maintenance of constant, internal environment of the body (homeo = same; stasis, = standing). Importance of internal environment was, notified by the great biologist of 19th century Claude, Bernard. He enlightened the fact that multicellular, organisms including man live in a perfectly organized and, controlled internal environment, which he called ‘milieu, interieur’. The word ‘homeostasis’ was introduced by, Harvard Professor, Walter B Cannon in 1930., Internal environment in the body is the extracellular, fluid (ECF) in which the cells live. It is the fluid outside, the cell and it constantly moves throughout the body. It, includes blood, which circulates in the vascular system, and fluid present in between the cells called interstitial, fluid. ECF contains nutrients, ions and all other, substances necessary for the survival of the cells., Normal healthy living of large organisms including, human beings depends upon the constant maintenance, of internal environment within the physiological limits. If, the internal environment deviates beyond the set limits,, body suffers from malfunction or dysfunction. Therefore,, the ultimate goal of an organism is to have a normal, healthy living, which is achieved by the maintenance of, internal environment within set limits., The concept of homeostasis forms basis of phy, siology because it explains why various physiological, functions are to be maintained within a normal range and, in case if any function deviates from this range how it is, , brought back to normal. Understanding the concept of, homeostasis also forms the basis for clinical diagnostic, procedures. For example, increased body temperature, beyond normal range as in the case of fever, indicates, that something is wrong in the heat production-heat loss, mechanism in the body. It induces the physician to go, through the diagnostic proceedings and decide about, the treatment., For the functioning of homeostatic mechanism, the, body must recognize the deviation of any physiological, activity from the normal limits. Fortunately, body is, provided with appropriate detectors or sensors, which, recognize the deviation. These detectors sense the, deviation and alert the integrating center. The integrating, center immediately sends information to the concerned, effectors to either accelerate or inhibit the activity so, that the normalcy is restored., , ROLE OF VARIOUS SYSTEMS OF THE, BODY IN HOMEOSTASIS, One or more systems are involved in homeostatic, mechanism of each function. Some of the functions in, which the homeostatic mechanism is well established, are given below:, 1. The pH of the ECF has to be maintained at the, critical value of 7.4. The tissues cannot survive if, it is altered. Thus, the decrease in pH (acidosis), or increase in pH (alkalosis) affects the tissues, markedly. The respiratory system, blood and kidney, help in the regulation of pH.
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Chapter 4 t Homeostasis, 2. Body temperature must be maintained at 37.5°C., Increase or decrease in temperature alters the, metabolic activities of the cells. The skin, respiratory, system, digestive system, excretory system,, skeletal muscles and nervous system are involved, in maintaining the temperature within normal limits., 3. Adequate amount of nutrients must be supplied, to the cells. Nutrients are essential for various, activities of the cell and growth of the tissues. These, substances also form the source of energy required, for various activities of the cells. Nutrients must be, digested, absorbed into the blood and supplied to, the cells. Digestive system and circulatory system, play major roles in the supply of nutrients., 4. Adequate amount of oxygen should be made, available to the cells for the metabolism of the, nutrients. Simultaneously, the carbon dioxide and, other metabolic end products must be removed., Respiratory system is concerned with the supply of, oxygen and removal of carbon dioxide. Kidneys and, other excretory organs are involved in the excretion, of waste products., 5. Many hormones are essential for the metabolism of, nutrients and other substances necessary for the, cells. Hormones are to be synthesized and released, from the endocrine glands in appropriate quantities, and these hormones must act on the body cells, appropriately. Otherwise, it leads to abnormal signs, and symptoms., 6. Water and electrolyte balance should be maintained, optimally. Otherwise it leads to dehydration or, water toxicity and alteration in the osmolality of, the body fluids. Kidneys, skin, salivary glands and, gastrointestinal tract take care of this., 7. For all these functions, the blood, which forms the, major part of internal environment, must be normal., It should contain required number of normal red, blood cells and adequate amount of plasma with, normal composition. Only then, it can transport the, nutritive substances, respiratory gases, metabolic, and other waste products., 8. Skeletal muscles are also involved in homeostasis., This system helps the organism to move around in, search of food. It also helps to protect the organism, from adverse surroundings, thus preventing damage, or destruction., 9. Central nervous system, which includes brain, and spinal cord also, plays an important role in, homeostasis. Sensory system detects the state, of the body or surroundings. Brain integrates and, interprets the pros and cons of these information, and commands the body to act accordingly through, , 39, , FIGURE 4.1: Components of homeostatic system, , motor system so that, the body can avoid the, damage., 10. Autonomic nervous system regulates all the, vegetative functions of the body essential for, homeostasis., , COMPONENTS OF HOMEOSTATIC SYSTEM, Homeostatic system in the body acts through selfregulating devices, which operate in a cyclic manner, (Fig. 4.1). This cycle includes four components:, 1. Sensors or detectors, which recognize the, deviation, 2. Transmission of this message to a control center, 3. Transmission of information from the control center, to the effectors for correcting the deviation, Transmission of the message or information may, be an electrical process in the form of impulses, through nerves or a chemical process mainly in the, form of hormones through blood and body fluids, 4. Effectors, which correct the deviation., , MECHANISM OF ACTION OF, HOMEOSTATIC SYSTEM, Homeostatic mechanism in the body is responsible, for maintaining the normalcy of various body systems., Whenever there is any change in behavioral pattern, of any system, the effectors bring back the normalcy, either by inhibiting and reversing the change or by, supporting and accelerating the change depending, upon requirement of the situation. This is achieved by, means of feedback signals.
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40, , Section 1 t General Physiology, , Feedback is a process in which some proportion of, the output signal of a system is fed (passed) back to the, input. This is done more often intentionally in order to, control the behavior pattern of the system. Whenever, any change occurs, system receives and reacts to two, types of feedback:, 1. Negative feedback, 2. Positive feedback., , NEGATIVE FEEDBACK, Negative feedback is the one to which the system, reacts in such a way as to arrest the change or reverse, the direction of change. After receiving a message,, effectors send negative feedback signals back to the, system. Now, the system stabilizes its own function and, makes an attempt to maintain homeostasis., , FIGURE 4.2: Negative feedback mechanism – secretion of thyroxine., TSH = Thyroid-stimulating hormone., , FIGURE 4.3: Negative feedback mechanism – maintenance of water balance., ADH = Antidiuretic hormone.
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Chapter 4 t Homeostasis, , 41, , FIGURE 4.4: Positive feedback mechanism – coagulation of, blood. Once formed, thrombin induces the formation of more, prothrombin activator., , Many homeostatic mechanisms in the body function, through negative feedback. For example, thyroid-stimulating hormone (TSH) released from pituitary gland stimulates thyroid gland to secrete thyroxine. When thyroxine, level increases in blood, it inhibits the secretion of TSH, from pituitary so that, the secretion of thyroxin from thyroid, gland decreases (Fig. 4.2). On the other hand, if thyroxine, secretion is less, its low blood level induces pituitary, gland to release TSH. Now, TSH stimulates thyroid, gland to secrete thyroxine (Refer Chapter 67 for details)., Another example for negative feedback mechanism is, maintenance of water balance in the body (Fig. 4.3)., POSITIVE FEEDBACK, Positive feedback is the one to which the system reacts, in such a way as to increase the intensity of the change, in the same direction. Positive feedback is less common, than the negative feedback. However, it has its own, significance particularly during emergency conditions., One of the positive feedbacks occurs during the, blood clotting. Blood clotting is necessary to arrest, bleeding during injury and it occurs in three stages., , FIGURE 4.5: Positive feedback mechanism – parturition, , The three stages are:, i. Formation of prothrombin activator, ii. Conversion of prothrombin into thrombin, iii. Conversion of fibrinogen into fibrin., Thrombin formed in the second stage stimulates, the formation of more prothrombin activator in addition, to converting fibrinogen into fibrin (Fig. 4.4). It causes, formation of more and more amount of prothrombin, activator so that the blood clotting process is accelerated, and blood loss is prevented quickly (Chapter 20). Other, processes where positive feedback occurs are milk, ejection reflex (Chapter 66) and parturition (Fig. 4.5), (Chapter 84) and both the processes involve oxytocin, secretion.
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Acid-base Balance, , Chapter, , 5, , INTRODUCTION, HYDROGEN ION AND pH, DETERMINATION OF ACID-BASE STATUS, REGULATION OF ACID-BASE BALANCE, , , , , DEFINITION, REGULATION OF ACID-BASE BALANCE BY RESPIRATORY MECHANISM, REGULATION OF ACID-BASE BALANCE BY RENAL MECHANISM, , DISTURBANCES OF ACID-BASE STATUS, , , , , , , , ACIDOSIS, ALKALOSIS, RESPIRATORY ACIDOSIS, RESPIRATORY ALKALOSIS, METABOLIC ACIDOSIS, METABOLIC ALKALOSIS, , CLINICAL EVALUATION – ANION GAP, , INTRODUCTION, Acid-base balance is very important for the homeostasis, of the body and almost all the physiological activities, depend upon the acid-base status of the body. Acids, are constantly produced in the body. However, the acid, production is balanced by the production of bases so, that the acid-base status of the body is maintained., An acid is the proton donor (the substance that, liberates hydrogen ion). A base is the proton acceptor, (the substance that accepts hydrogen ion)., In spite of continuous production of acids in the, body, the concentration of free hydrogen ion is kept, almost constant at a pH of 7.4 with slight variations., , HYDROGEN ION AND pH, Hydrogen ion (H+) contains only a single proton (positively, charged particle), which is not orbited by any electron., Therefore, it is the smallest ionic particle. However, it is, highly reactive. Because of this, the H+ shows severe, effects on the physiological activities of the body even at, , low concentrations. The normal H+ concentration in the, extracellular fluid (ECF) is 38 to 42 nM/L., The pH is another term for H+ concentration that, is generally used nowadays instead of ‘hydrogen ion, concentration’. The pH scale was introduced in order, to simplify the mathematical handling of large numbers., Negative logarithm of H+ concentration is taken for, calculating the pH as given below., , An increase in H+ ion concentration decreases, the pH (acidosis) and a reduction in H+ concentration, increases the pH (alkalosis). An increase in pH by onefold requires a tenfold decrease in H+ concentration, (Table 5.1)., In a healthy person, the pH of the ECF is 7.40 and it, varies between 7.38 and 7.42. The maintenance of acidbase status is very important for homeostasis, because, even a slight change in pH below 7.38 or above 7.42 will, cause serious threats to many physiological functions.
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Chapter 5 t Acid-base Balance, TABLE 5.1: Hydrogen ion concentration and pH, +, , H (nM/L), , pH, , 10,000, , 5.0, , 1,000, , 6.0, , 100, , 7.0, , 10, , 8.0, , 1, , 9.0, , DETERMINATION OF ACID-BASE STATUS, It is difficult to determine the acid-base status in the, ECF by direct methods. So, an indirect method is, followed by using Henderson-Hasselbalch equation. In, this, to determine the pH of a fluid, the concentration of, bicarbonate ions (HCO3–) and the CO2 dissolved in the, fluid are measured. The pH is calculated as follows:, , Where, pK is constant with pH of 6.1, Thus,, , In addition to this, the pH of plasma is also determined, by using an instrument called pH meter., Normal acid-base ratio is 1:20, i.e. the ratio of 1 part, of CO2 (derived from H2CO3) and 20 parts of HCO3–., If this ratio is altered, the pH also is altered leading to, either acidosis or alkalosis., Thus, the pH of arterial blood is an indirect, measurement of H+ concentration and it reflects the, balance of CO2 and HCO3–., , REGULATION OF ACID-BASE BALANCE, Body is under constant threat of acidosis because of, the production of large amount of acids. Generally, two, types of acids are produced in the body:, 1. Volatile acids, 2. Non-volatile acids., 1. Volatile Acids, Volatile acids are derived from CO2. Large quantity of, CO2 is produced during the metabolism of carbohydrates, and lipids. This CO2 is not a threat because it is almost, totally removed through expired air by lungs., 2. Non-volatile Acids, Non-volatile acids are produced during the metabolism, of other nutritive substances such as proteins. These, , 43, , acids are real threat to the acid-base status of the, body. For example, sulfuric acid is produced during the, metabolism of sulfur containing amino acids such as, cysteine and metheonine; hydrochloric acid is produced, during the metabolism of lysine, arginine and histidine., Fortunately, body is provided with the best regulatory, mechanisms to prevent the hazards of acid production., Compensatory Mechanism, Whenever there is a change in pH beyond the normal, range, some compensatory changes occur in the body, to bring the pH back to normal level. The body has three, different mechanisms to regulate acid-base status:, 1. Acid-base buffer system, which binds free H+, 2. Respiratory mechanism, which eliminates CO2, 3. Renal mechanism, which excretes H+ and conserves, the bases (HCO3–)., Among the three mechanisms, the acid-base buffer, system is the fastest one and it readjusts the pH within, seconds. The respiratory mechanism does it in minutes., Whereas, the renal mechanism is slower and it takes, few hours to few days to bring the pH back to normal., However, the renal mechanism is the most powerful, mechanism than the other two in maintaining the acidbase balance of the body fluids., , REGULATION OF ACID-BASE BALANCE, BY ACID-BASE BUFFER SYSTEM, DEFINITION, An acid-base buffer system is the combination of a, weak acid (protonated substance) and a base – the salt, (unprotonated substance). Buffer system is the one,, which acts immediately to prevent the changes in pH., Buffer system maintains pH by binding with free H+., Types of Buffer Systems, Body fluids have three types of buffer systems, which, act under different conditions:, 1. Bicarbonate buffer system, 2. Phosphate buffer system, 3. Protein buffer system., 1. Bicarbonate Buffer System, Bicarbonate buffer system is present in ECF (plasma)., It consists of the protonated substance, carbonic acid, (H2CO3) which is a weak acid and the unprotonated, substance, HCO3–, which is a weak base. HCO3– is in, the form of salt, i.e. sodium bicarbonate (NaHCO3).
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44, , Section 1 t General Physiology, , Mechanism of action of bicarbonate buffer system, Bicarbonate buffer system prevents the fall of pH in a, fluid to which a strong acid like hydrochloric acid (HCl), is added., Normally, when HCl is mixed with a fluid, pH of, that fluid decreases quickly because the strong HCl, dissociates into H+ and Cl–., But, if bicarbonate buffer system (NaHCO3) is, added to the fluid with HCl, the pH is not altered much., This is because the H+ dissociated from HCl combines, with HCO3– of NaHCO3 and forms a weak H2CO3. This, H2CO3 in turn dissociates into CO2 and H2O., HCl + NaHCO3 → H2CO3 + NaCl, , ↓, , CO2 + H2O, Bicarbonate buffer system also prevents the, increase in pH in a fluid to which a strong base like, sodium hydroxide (NaOH) is added., Normally, when a base (NaOH) is added to a fluid,, pH increases. It is prevented by adding H2CO3, which, dissociates into H+ and HCO3–. The hydroxyl group (OH), of NaOH combines with H+ and forms H2O. And Na+, combines with HCO3– and forms NaHCO3. NaHCO3 is, a weak base and it prevents the increase in pH by the, strong NaOH., As sodium bicarbonate is a very weak base, its, association with H+ is poor. So the rise in pH of the fluid, is very mild., Importance of bicarbonate buffer system, Bicarbonate buffer system is not powerful like the other, buffer systems because of the large difference between, the pH of ECF (7.4) and the pK of bicarbonate buffer, system (6.1). But this buffer system plays an important, role in maintaining the pH of body fluids than the other, buffer systems. It is because the concentration of two, components (HCO3– and CO2) of this buffer system is, regulated separately by two different mechanisms., Concentration of HCO3– is regulated by kidney and, the concentration of CO2 is regulated by the respiratory, system. These two regulatory mechanisms operate constantly and simultaneously, making this system more, effective., 2. Phosphate Buffer System, This system consists of a weak acid, the dihydrogen, phosphate (H2PO4 – protonated substance) in the, form of sodium dihydrogen phosphate (NaH2PO4) and, the base, hydrogen phosphate (HPO4 – unprotonated, substance) in the form of disodium hydrogen phosphate, (Na2HPO4)., , Phosphate buffer system is useful in the intracellular, fluid (ICF), in red blood cells or other cells, as the concentration of phosphate is more in ICF than in ECF., Mechanism of phosphate buffer system, When a strong acid like hydrochloric acid is mixed with, a fluid containing phosphate buffer, sodium dihydrogen, phosphate (NaH2PO4 – weak acid) is formed. This, permits only a mild change in the pH of the fluid., HCl, + Na2HPO4 → NaH2PO4 + NaCl, (strong acid), (weak acid), If a strong base such as sodium hydroxide (NaOH), is added to the fluid containing phosphate buffer, a weak, base called disodium hydrogen phosphate (Na2HPO4) is, formed. This prevents the changes in pH., NaOH, + NaH2PO4 → NaHPO4 + H2O, (strong base), (weak base), Importance of phosphate buffer system, Phosphate buffer system is more powerful than, bicarbonate buffer system as it has a pK of 6.8, which, is close to the pH of the body fluids, i.e. 7.4. In addition, to ICF, phosphate buffer is useful in tubular fluids of, kidneys also. It is because more phosphate ions are, found in tubular fluid., In the red blood cells, the potassium ion concentration, is higher than the sodium ion concentration. So, the, elements of phosphate buffer inside the red blood cells, are in the form of potassium dihydrogen phosphate, (KH2PO4) and dipotassium hydrogen phosphate, (K2HPO4)., 3. Protein Buffer System, Protein buffer systems are present in the blood; both in, the plasma and erythrocytes., Protein buffer systems in plasma, Elements of proteins, which form the weak acids in the, plasma are:, i. C-terminal carboxyl group, N-terminal amino, group and side-chain carboxyl group of glutamic, acid, ii. Side-chain amino group of lysine, iii. Imidazole group of histidine., Protein buffer systems in plasma are more powerful, because of their high concentration in plasma and, because of their pK being very close to 7.4., Protein buffer system in erythrocytes (Hemoglobin), Hemoglobin is the most effective protein buffer and the, major buffer in blood. Due to its high concentration than
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Chapter 5 t Acid-base Balance, the plasma proteins, hemoglobin has about six times, more buffering capacity than the plasma proteins. The, deoxygenated hemoglobin is a more powerful buffer, than oxygenated hemoglobin because of the higher pK., When a hemoglobin molecule becomes deoxygenated in, the capillaries, it easily binds with H+, which are released, when CO2 enters the capillaries. Thus, hemoglobin, prevents fall in pH when more and more CO2 enters the, capillaries., REGULATION OF ACID-BASE BALANCE, BY RESPIRATORY MECHANISM, Lungs play an important role in the maintenance of, acid-base balance by removing CO2 which is produced, during various metabolic activities in the body. This CO2, combines with water to form carbonic acid., Since carbonic acid is unstable, it splits into H+ and, HCO3–., CO2 + H2O → H2CO3 → H+ + HCO3–, Entire reaction is reversed in lungs when CO2, diffuses from blood into the alveoli of lungs., H+ + HCO3– → H2CO3 → CO2 + H2O, And CO2 is blown off by ventilation (Chapter 125)., When metabolic activities increase, more amount of, CO2 is produced in the tissues and the concentration of, H+ increases as seen above. Increased H+ concentration, increases the pulmonary ventilation (hyperventilation), by acting through the chemoreceptors (Chapter 126)., Due to hyperventilation, the excess of CO2 is removed, from the body., , 45, , APPLIED PHYSIOLOGY – DISTURBANCES, OF ACID-BASE STATUS, ACIDOSIS, Acidosis is the reduction in pH (increase in H+, concentration) below normal range., Acidosis is produced by:, 1. Increase in partial pressure of CO2 in the body fluids, particularly in arterial blood, 2. Decrease in HCO3– concentration., ALKALOSIS, Alkalosis is the increase in pH (decrease in H+ concentration) above the normal range (Table 5.2)., Alkalosis is produced by:, 1. Decrease in partial pressure of CO2 in the arterial, blood, 2. Increase in HCO3– concentration., Since the partial pressure of CO2 (pCO2) in arterial, blood is controlled by lungs, the acid-base disturbances, produced by the change in arterial pCO2 are called the, respiratory disturbances., On the other hand, the disturbances in acid-base, status produced by the change in HCO3– concentration, are generally called the metabolic disturbances., Thus the acid-base disturbances are:, 1. Respiratory acidosis, 2. Respiratory alkalosis, 3. Metabolic acidosis, 4. Metabolic alkalosis., RESPIRATORY ACIDOSIS, , REGULATION OF ACID-BASE BALANCE BY, RENAL MECHANISM, Kidney maintains the acid-base balance of the body by, the secretion of H+ and by the retention of HCO3– (Fig., 5.1). Details are given in Chapter 54., , Respiratory acidosis is the acidosis that is caused, by alveolar hypoventilation. During hypoventilation, the lungs fail to expel CO2, which is produced in the, tissues. CO2 is the major end product of oxidation of, carbohydrates, proteins and fats., , FIGURE 5.1: Regulation of acid-base balance
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Section 1 t General Physiology, , 46, , CO2 accumulates in blood where it reacts with, water to form carbonic acid, which is called respiratory, acid. Carbonic acid dissociates into H+ and HCO3–. The, increased H+ concentration in blood leads to decrease, in pH and acidosis., Normal partial pressure of CO2 in arterial blood is, about 40 mm Hg. When it increases above 60 mm Hg, acidosis occurs., , Hyperventilation is primary cause for loss of excess CO2, from the body because during hyperventilation, lot of CO2, is expired through respiratory tract leading to decreased, pCO2. Some of the conditions when decreased pCO2, and respiratory alkalosis occur due to hyperventilation, are given in Table 5.4., , Causes of Excess CO2 in the Body, , METABOLIC ACIDOSIS, , Hypoventilation (decreased ventilation) is the primary, cause for excess CO2 in the body. Some of the conditions, when increase in pCO2 and respiratory acidosis occur, due to hypoventilation are listed in Table 5.3., , Metabolic acidosis is the acid-base imbalance, characterized by excess accumulation of organic acids, in the body, which is caused by abnormal metabolic, processes. Organic acids such as lactic acid, ketoacids, and uric acid are formed by normal metabolism. The, quantity of these acids increases due to abnormality in, the metabolism., , RESPIRATORY ALKALOSIS, Respiratory alkalosis is the alkalosis that is caused, by alveolar hyperventilation. Hyperventilation causes, excess loss of CO2 from the body. Loss of CO2 leads, to decreased formation of carbonic acid and decreased, release of H+. Decreased H+ concentration increases, the pH leading to respiratory alkalosis., When the partial pressure of CO2 in arterial blood, decreases below 20 mm Hg, alkalosis occurs., , Causes of Decrease in CO2 in the Body, , Causes of Metabolic Acidosis, Lactic acid, The amount of lactic acid increases during anaerobic, glycolysis in some abnormal conditions such as, circulatory shock., , TABLE 5.2: Biochemical changes in arterial blood during acid-base disturbance, Acidosis, Parameter, +, , Respiratory, , Alkalosis, Metabolic, , Respiratory, , Metabolic, , H, , Increases, , Increases, , Decreases, , Decreases, , pH, , Decreases, , Decreases, , Increases, , Increases, , Increases, , Decreases, , Decreases, , Increases, , Increases slightly, , Decreases very much, , Decreases slightly, , Increases very much, , pCO2, HCO3, , –, , TABLE 5.3: Causes of acidosis, Respiratory acidosis, , Metabolic acidosis, , 1. Airway obstruction due to bronchitis, bronchospasm,, emphysema, etc., , 1. Lactic acidosis as in circulatory shock, , 2. Lung diseases like fibrosis, pneumonia, etc., , 2. Ketoacidosis as in diabetes mellitus, , 3. Respiratory center depression by anesthetics, sedatives,, cerebral trauma, tumors, etc., , 3. Uric acidosis as in renal failure, , 4. Extrapulmonary thoracic diseases like flail chest,, kyphosis and scoliosis, , 4. Acid poisoning, , 5. Neural diseases like polymyelitis, paralysis of respiratory, muscles, , 5. Renal tubular acidosis due to decreased H+ excretion, 6. Loss of excess HCO3– due to diarrhea and pancreatic,, intestinal, or biliary fistula
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Chapter 5 t Acid-base Balance, , 47, , TABLE 5.4: Causes of alkalosis, Respiratory alkalosis, , Metabolic alkalosis, , 1. Hypoxia as in high altitude, severe anemia and, pulmonary diseases like edema and embolism, 2. Increased respiratory drive due to cerebral disturbances,, voluntary hyperventilation and psychological and, emotional trauma, , 1. Vomiting and congenital diarrhea, 2. Endocrine disorders such as Cushing’s syndrome and, Conn’s syndrome, 3. Diuretic therapy, , TABLE 5.5: Variations in anion gap, Increase in anion gap, , Decrease in anion gap, , 1. Metabolic disorder (inability to metabolize lactic acid), , 1. Hyperchloremic acidosis (increased chloride level in blood), , 2. Dehydration, , 2. Hypoalbuminemia (low albumin level in blood), , 3. Diabetes, starvation, alcoholism (due to increased, production of ketoacid), , 3. Multiple myeloma (due to accumulation of anionic proteins), , 4. Renal disease (failure to excrete acids – phosphate and, sulfate), , 4. Hyponatremia (low blood sodium level), , 5. Respiratory disease (production of excess lactic acid due, to inadequate oxygen supply to tissues), , 5. Renal disease (loss of excess sodium or potassium, through urine), , 6. Genetic disorder (involving enzymes of carbohydrate, metabolism), , 6. Hyperthyroidism, , 7. Nutritional deficiencies, , 7. Toxicity due to lithium or bromide, , Ketoacids, The amount of ketoacids increases because of insulin, deficiency as in the case of diabetes mellitus. In, diabetes mellitus, glucose is not utilized due to lack of, insulin. So, lipids are utilized for liberation of energy, resulting in production of excess acetoacetic acid and, beta hydroxybutyric acid., Uric acid, The amount of uric acid increases in the body due to, the failure of excretion. Normally uric acid is excreted, by kidneys. But in renal diseases, the kidneys fail to, excrete the uric acid., Some of the conditions when the metabolic acids, increase in the body resulting in metabolic acidosis are, listed in Table 5.3., METABOLIC ALKALOSIS, Metabolic alkalosis is the acid-base imbalance caused, by loss of excess H+ resulting in increased HCO3–, concentration. Some of the endocrine disorders, renal, tubular disorders, etc. cause metabolic disorders, leading to loss of H+. It increases HCO3– and pH in the, body leading to metabolic alkalosis., Some of the conditions when excess H+ is lost and, HCO3– content increases leading to metabolic alkalosis, are given in Table 5.4., , CLINICAL EVALUATION OF, DISTURBANCES IN ACID-BASE, STATUS – ANION GAP, Anion gap is an important measure in the clinical, evaluation of disturbances in acid-base status. Only, few cations and anions are measured during routine, clinical investigations. Commonly measured cation is, sodium and the unmeasured cations are potassium,, calcium and magnesium. Usually measured anions are, chloride and bicarbonate. The unmeasured anions are, phosphate, sulfate, proteins in anionic form such as, albumin and other organic anions like lactate., Difference between concentrations of unmeasured, anions and unmeasured cations is called anion gap., It is calculated as:, Anion gap = [Na+] – [HCO3–] – [Cl–], = 144 – 24 – 108 mEq/L, = 12 mEq/L, Normal value of anion gap is 9 to 15 mEq/L. It, increases when concentration of unmeasured anion, increases and decreases when concentration of, unmeasured cations decreases., Anion gap is a useful measure in the differential, diagnosis (diagnosis of the different causes) of acidbase disorders particularly the metabolic acidosis., Variations of anion gap are given in Table 5.5.
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48, , Questions in General Physiology, , QUESTIONS IN GENERAL PHYSIOLOGY, , LONG QUESTIONS, 1. Describe the mechanism of active transport of, substances through cell membrane., 2. Describe the mechanism of passive transport of, substances through cell membrane., 3. Explain the regulation of acid-base balance. Add, a note on disturbances of acid-base balance., 4. Explain the homeostasis in the body with, suitable examples., , SHORT QUESTIONS, 1., 2., 3., 4., 5., 6., 7., 8., 9., 10., 11., 12., 13., 14., , Cell membrane., Proteins of cell membrane., Organelles present in the cytoplasm of the cell., Endoplasmic reticulum., Ribosomes., Mitochondria., Golgi apparatus., RNA., DNA., Cellular organelles taking part in protective, function., Apoptosis., Cellular necrosis., Tight junctions., Gap junctions., , 15., 16., 17., 18., 19., 20., 21., 22., 23., 24., 25., 26., 27., 28., 29., 30., 31., 32., 33., 34., 35., 36., 37., 38., , Passive transport., Active transport., Primary active transport., Secondary active transport., Sodium-potassium pump., Simple diffusion through cell membrane., Facilitated diffusion or carrier-mediated diffusion., Ion channels., Factors affecting diffusion., Pinocytosis., Phagocytosis., Transcytosis., Receptor-mediated endocytosis., Homeostasis., Components of homeostasis., Negative feedback., Positive feedback., Acid-base buffer system., Role of blood in the maintenance of acid-base, balance or acid-base buffer system., Role of lungs in the maintenance of acid-base, balance., Role of kidneys in the maintenance of acid-base, balance., Acidosis., Alkalosis., Anion gap.
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Section, , 2, , 6., 7., 8., 9., 10., 11., 12., 13., 14., 15., 16., 17., 18., 19., 20., 21., 22., , Blood and, Body Fluids, , Body Fluids ............................................................................................... 51, Blood ......................................................................................................... 58, Plasma Proteins ........................................................................................ 61, Red Blood Cells ........................................................................................ 66, Erythropoiesis ........................................................................................... 71, Hemoglobin and Iron Metabolism ............................................................. 77, Erythrocyte Sedimentation Rate ............................................................... 83, Packed Cell Volume and Blood Indices .................................................... 86, Anemia ...................................................................................................... 89, Hemolysis and Fragility of Red Blood Cells .............................................. 95, White Blood Cells ...................................................................................... 97, Immunity .................................................................................................. 107, Platelets .................................................................................................. 122, Hemostasis ............................................................................................. 127, Coagulation of Blood ............................................................................... 129, Blood Groups .......................................................................................... 139, Blood Transfusion ................................................................................... 146
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23., 24., 25., 26., 27., , Blood Volume .......................................................................................... 148, Reticuloendothelial System and Tissue Macrophage ............................. 151, Spleen ..................................................................................................... 153, Lymphatic System and Lymph ................................................................ 155, Tissue Fluid and Edema ......................................................................... 159
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Chapter, , Body Fluids, , , , , , , , , , 6, , INTRODUCTION, SIGNIFICANCE, COMPARTMENTS, COMPOSITION, MEASUREMENT, CONCENTRATION, MAINTENANCE OF WATER BALANCE, APPLIED PHYSIOLOGY, , INTRODUCTION, , IN TRANSPORT MECHANISM, , Body is formed by solids and fluids. Fluid part is more, than two third of the whole body. Water forms most of, the fluid part of the body., In human beings, the total body water varies from, 45% to 75% of body weight. In a normal young adult, male, body contains 60% to 65% of water and 35% to, 40% of solids. In a normal young adult female, the water, is 50% to 55% and solids are 45% to 50%. In females,, water is less because of more amount of subcutaneous, adipose tissue. In thin persons, water content is more, than that in obese persons. In old age, water content, is decreased due to increase in adipose tissue. Total, quantity of body water in an average human being, weighing about 70 kg is about 40 L., , Body water forms the transport medium by which, nutrients and other essential substances enter the cells;, and unwanted substances come out of the cells. Water, forms an important medium by which various enzymes,, hormones, vitamins, electrolytes and other substances, are carried from one part to another part of the body., IN METABOLIC REACTIONS, Water inside the cells forms the medium for various, metabolic reactions, which are necessary for growth and, functional activities of the cells., IN TEXTURE OF TISSUES, Water inside the cells is necessary for characteristic, form and texture of various tissues., , SIGNIFICANCE OF BODY FLUIDS, IN HOMEOSTASIS, Body cells survive in the fluid medium called internal, environment or ‘milieu interieur’. Internal environment, contains substances such as glucose, amino acids,, lipids, vitamins, ions, oxygen, etc. which are essential, for growth and functioning of the cell. Water not only, forms the major constituent of internal environment but, also plays an important role in homeostasis., , IN TEMPERATURE REGULATION, Water plays a vital role in the maintenance of normal, body temperature., , COMPARTMENTS OF BODY FLUIDS –, DISTRIBUTION OF BODY FLUIDS, Total water in the body is about 40 L. It is distributed into, two major compartments:
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52, , Section 2 t Blood and Body Fluids, , 1. Intracellular fluid (ICF): Its volume is 22 L and it, forms 55% of the total body water, 2. Extracellular fluid (ECF): Its volume is 18 L and it, forms 45% of the total body water., ECF is divided into 5 subunits:, i. Interstitial fluid and lymph (20%), ii. Plasma (7.5%), iii. Fluid in bones (7.5%), iv. Fluid in dense connective tissues like cartilage, (7.5%), v. Transcellular fluid (2.5%) that includes:, a. Cerebrospinal fluid, b. Intraocular fluid, c. Digestive juices, d. Serous fluid – intrapleural fluid, pericardial, fluid and peritoneal fluid, e. Synovial fluid in joints, f. Fluid in urinary tract., Volume of interstitial fluid is about 12 L. Volume of, plasma is about 2.75 L. Volume of other subunits of, ECF is about 3.25 L. Water moves between different, compartments (Fig. 6.1)., , COMPOSITION OF BODY FLUIDS, Body fluids contain water and solids. Solids are organic, and inorganic substances., ORGANIC SUBSTANCES, Organic substances are glucose, amino acids and other, proteins, fatty acids and other lipids, hormones and, enzymes., , FIGURE 6.1: Body fluid compartments and movement of fluid, between different compartments. Other fluids = Transcellular, fluid, fluid in bones and fluid in connective tissue., , INDICATOR DILUTION METHOD, , INORGANIC SUBSTANCES, , Principle, , Inorganic substances present in body fluids are sodium,, potassium, calcium, magnesium, chloride, bicarbonate,, phosphate and sulfate., ECF contains large quantity of sodium, chloride,, bicarbonate, glucose, fatty acids and oxygen. ICF, contains large quantities of potassium, magnesium,, phosphates, sulfates and proteins. The pH of ECF is, 7.4. The pH of ICF is 7.0. Differences between ECF and, ICF are given in Table 6.1., , A known quantity of a substance such as a dye is, administered into a specific body fluid compartment., These substances are called the marker substances or, indicators. After administration into the fluid compartment, the substance is allowed to mix thoroughly with, the fluid. Then, a sample of fluid is drawn and the, concentration of the marker substance is determined., Radioactive substances or other substances whose, concentration can be determined by using colorimeter, are generally used as marker substances (Table 6.2)., , MEASUREMENT OF BODY FLUID VOLUME, , Formula to Measure the Volume of Fluid by, Indicator Dilution Method, , Total body water and the volume of different compartments of the body fluid are measured by indicator dilution, method or dye dilution method., , Quantity of fluid in the compartment is measured using, the formula:
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Chapter 6 t Body Fluids, , V = Volume of fluid in the compartment., M = Mass or total quantity of marker substance, injected., C = Concentration of the marker substance in the, sample fluid, Correction factor, Some amount of marker substance is lost through, urine during distribution. So, the formula is corrected as, follows:, M – Amount of substance excreted, Volume =, C, Uses of Indicator Dilution Method, Indicator dilution or dye dilution method is used to, measure ECF volume, plasma volume and the volume, of total body water., Characteristics of Marker Substances, Dye or any substance used as a marker substance, should have the following qualities:, 1. Must be nontoxic, TABLE 6.1: Differences between extracellular fluid (ECF), and intracellular fluid (ICF), Substance, , ECF, , ICF, , Sodium, , 142 mEq/L, , 10 mEq/L, , Calcium, , 5 mEq/L, , 1 mEq/L, , Potassium, , 4 mEq/L, , 140 mEq/L, , 53, , 2. Must mix with the fluid compartment thoroughly, within reasonable time, 3. Should not be excreted rapidly, 4. Should be excreted from the body completely within, reasonable time, 5. Should not change the color of the body fluid, 6. Should not alter the volume of the body fluid., Marker Substances Used to, Measure Fluid Compartments, Marker substances used to measure different fluid, compartment are listed in Table 6.2., MEASUREMENT OF TOTAL BODY WATER, Volume of total body water (fluid) is measured by using, a marker substance which is distributed through all the, compartments of body fluid. Such substances are listed, in Table 6.2., Deuterium oxide and tritium oxide mix with fluids, of all the compartments within few hours after injection., Since plasma is part of total body fluid, the concentration, of marker substances can be obtained from sample of, plasma. The formula for indicator dilution method is, applied to calculate total body water., Antipyrine is also used to measure total body water., But as it takes longer time to penetrate various fluid, compartments, the value obtained is slightly low., MEASUREMENT OF EXTRACELLULAR, FLUID VOLUME, , 0.5 g/dL, , 2-95 g/dL, , Partial pressure of, oxygen, , 35 mm Hg, , 20 mm Hg, , Substances which pass through the capillary membrane, but do not enter the cells, are used to measure ECF, volume. Such marker substances are listed in Table 6.2., These substances remain only in ECF and do not enter, the cell (ICF). When any of these substances is injected, into blood, it mixes with the fluid of all subcompartments, of ECF within 30 minutes to 1 hour. Indicator dilution, method is applied to calculate ECF volume. Since ECF, includes plasma, the concentration of marker substance, can be obtained in the sample of plasma., Some of the marker substances like sodium, chloride,, inulin and sucrose diffuse more evenly throughout all, subcompartments of ECF. So, the measured volume of, ECF by using these substances is referred as sodium, space, chloride space, inulin space and sucrose space., , Partial pressure of, carbon dioxide, , 46 mm Hg, , 50 mm Hg, , Example for Measurement of ECF Volume, , 15 to 20 L (18), , 20 to 25 L (22), , 7.4, , 7.0, , Magnesium, , 3 mEq/L, , 28 mEq/L, , 103 mEq/L, , 4 mEq/L, , Bicarbonate, , 28 mEq/L, , 10 mEq/L, , Phosphate, , 4 mEq/L, , 75 mEq/L, , Sulfate, , 1 mEq/L, , 2 mEq/L, , Chloride, , Proteins, , 2 g/dL, , 16 g/dL, , Amino acids, , 30 mg/dL, , 200 mg/dL, , Glucose, , 90 mg/dL, , 0-20 mg/dL, , Lipids, , Water, pH, , Quantity of sucrose injected (Mass), Urinary excretion of sucrose, Concentration of sucrose in plasma, , : 150 mg, : 10 mg, : 0.01 mg/mL
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54, , Section 2 t Blood and Body Fluids, TABLE 6.2: Marker substances used to measure body, fluid compartments, , Sucrose space =, =, , Mass – Amount lost in urine, , Fluid compartment, Total body water, , 1. Deuterium oxide (D2O), 2. Tritium oxide (T2O), 3. Antipyrine, , Extracellular fluid, , 1. Radioactive sodium, chloride,, bromide, sulfate and thiosulfate., 2. Non-metabolizable saccharides, like inulin, mannitol, raffinose, and sucrose, , Plasma, , 1. Radioactive iodine (131I), 2. Evans blue (T-1824), , Concentration of sucrose in plasma, 150 – 10 mg, , 0.01 mg/mL, = 14,000 mL, , Therefore, the ECF volume = 14 L., MEASUREMENT OF PLASMA VOLUME, The substance which binds with plasma proteins strongly, and diffuses into interstitium only in small quantities or, does not diffuse is used to measure plasma volume., Such substances are listed in Table 6.2., (Measurement of plasma volume and blood volume, is explained in chapter 23)., MEASUREMENT OF INTERSTITIAL, FLUID VOLUME, Volume of interstitial fluid cannot be measured directly. It, is calculated from the values of ECF volume and plasma, volume., Interstitial fluid volume =, ECF volume – Plasma volume, MEASUREMENT OF INTRACELLULAR, FLUID VOLUME, Volume of ICF cannot be measured directly. It is calculated from the values of total body water and ECF., ICF volume = Total fluid volume – ECF volume., , Marker substances, , OSMOLARITY, Osmolarity is another term to express the osmotic, concentration. It is the number of particles (osmoles) per, liter of solution (osmoles/L)., Osmotic pressure in solutions depends upon, osmolality. However, in practice, the osmolarity and, not osmolality is considered to determine the osmotic, pressure because of the following reasons:, i. Measurement of weight (kilogram) of water in, solution is a difficult process, ii. Difference between osmolality and osmolarity is, very much negligible and it is less than 1%., Often, these two terms are used interchangeably., Change in osmolality of ECF affects the volume of, both ECF and ICF. When osmolality of ECF increases,, water moves from ICF to ECF. When the osmolality, decreases in ECF, water moves from ECF to ICF. Water, movement continues until the osmolality of these two, fluid compartments becomes equal., Mole and Osmole, , CONCENTRATION OF BODY FLUIDS, Concentration of body fluids is expressed in three, ways:, 1. Osmolality, 2. Osmolarity, 3. Tonicity., OSMOLALITY, Measure of a fluid’s capability to create osmotic pressure, is called osmolality or osmotic (osmolar) concentration, of a solution. In simple words, it is the concentration of, osmotically active substance in the solution. Osmolality, is expressed as the number of particles (osmoles) per, kilogram of solution (osmoles/kg H2O)., , A mole (mol) is the molecular weight of a substance in, gram. Millimole (mMol) is 1/1000 of a mole. One osmole, (Osm) is the expression of amount of osmotically active, particles. It is the molecular weight of a substance in, grams divided by number of freely moving particles, liberated in solution of each molecule. One milliosmole, (mOsm) is 1/1000 of an osmole., TONICITY, Usually, movement of water between the fluid, compartments is not influenced by small molecules like, urea and alcohol, which cross the cell membrane very, rapidly. These small molecules are called ineffective, osmoles. On the contrary, the larger molecules like
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Chapter 6 t Body Fluids, sodium and glucose, which cross the cell membrane, slowly, can influence the movement of water. Therefore,, such molecules are called effective osmoles. Osmolality, that causes the movement of water from one compartment, to another is called effective osmolality and the effective, osmoles are responsible for this., Tonicity is the measure of effective osmolality. In, terms of tonicity, the solutions are classified into three, categories:, i. Isotonic fluid, ii. Hypertonic fluid, iii. Hypotonic fluid., i. Isotonic Fluid, Fluid which has the same effective osmolality (tonicity), as body fluids is called isotonic fluid. Examples are 0.9%, sodium chloride solution (normal saline) and 5% glucose, solution., Red blood cells or other cells placed in isotonic fluid, (normal saline) neither gain nor lose water by osmosis, (Fig. 6.2). This is because of the osmotic equilibrium, between inside and outside the cell across the cell, membrane., ii. Hypertonic Fluid, Fluid which has greater effective osmolality than the, body fluids is called hypertonic fluid. Example is 2%, sodium chloride solution., When red blood cells or other cells are placed in, hypertonic fluid, water moves out of the cells (exosmosis), resulting in shrinkage of the cells (crenation). Refer, Figure 6.2, iii. Hypotonic Fluid, Fluid which has less effective osmolality than the body, fluids is called hypotonic fluid. Example is 0.3% sodium, chloride solution., When red blood cells or other cells are placed in, hypotonic fluid, water moves into the cells (endosmosis), and causes swelling of the cells (Fig. 6.2). Now the red, blood cells become globular (sphereocytic) and get, ruptured (hemolysis)., , MAINTENANCE OF WATER BALANCE, Body has several mechanisms which work together to, maintain the water balance. The important mechanisms, involve hypothalamus (Chapters 4, 149) and kidneys, (Chapter 53)., , 55, , FIGURE 6.2: Effect of isotonic, hypertonic and hypotonic, solutions on red blood cells, , APPLIED PHYSIOLOGY, DEHYDRATION, Definition, Dehydration is defined as excessive loss of water from, the body. Body requires certain amount of fluid intake, daily for normal functions. Minimum daily requirement, of water intake is about 1 L. This varies with the age, and activity of the individual. The most active individuals, need 2 to 3 L of water intake daily. Dehydration occurs, when fluid loss is more than what is consumed., Classification, Basically, dehydration is of three types:, 1. Mild dehydration: It occurs when fluid loss is about, 5% of total body fluids. Dehydration is not very, serious and can be treated easily by rehydration., 2. Moderate dehydration: It occurs when fluid loss, is about 10%. Dehydration becomes little serious, and immediate treatment should be given by, rehydration., 3. Severe dehydration: It occurs when fluid loss is, about 15%. Dehydration becomes severe and, requires hospitalization and emergency treatment., When fluid loss is more than 15%, dehydration, becomes very severe and life threatening., On the basis of ratio between water loss and sodium, loss, dehydration is classified into three types:, 1. Isotonic dehydration: Balanced loss of water and, sodium as in the case of diarrhea or vomiting., 2. Hypertonic dehydration: Loss of more water than, sodium as in the case of fever., 3. Hypotonic dehydration: Loss of more sodium than, water as in the case of excess use of diuretics.
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56, , Section 2 t Blood and Body Fluids, , Causes, 1. Severe diarrhea and vomiting due to gastrointestinal, disorders, 2. Excess urinary output due to renal disorders, 3. Excess loss of water through urine due to endocrine, disorders such as diabetes mellitus, diabetes, insipidus and adrenal insufficiency, 4. Insufficient intake of water, 5. Prolonged physical activity without consuming, adequate amount of water in hot environment, 6. Excess sweating leading to heat frustration, (extreme loss of water, heat and energy). Severe, sweating and dehydration occur while spending, longer periods on regular basis in the saunas, 7. Use of laxatives or diuretics in order to lose weight, quickly. This is common in athletes., Signs and Symptoms, Mild and moderate dehydration, 1., 2., 3., 4., 5., 6., 7., 8., , Dryness of the mouth, Excess thirst, Decrease in sweating, Decrease in urine formation, Headache, Dizziness, Weakness, Cramps in legs and arms., , Severe dehydration, 1., 2., 3., 4., 5., , Decrease in blood volume, Decrease in cardiac output, Low blood pressure, Hypovolemic cardiac shock, Fainting., , Very severe dehydration, 1., 2., 3., 4., 5., , Damage of organs like brain, liver and kidneys, Mental depression and confusion, Renal failure, Convulsions, Coma., , Dehydration in Infants, Infants suffering from severe diarrhea and vomiting, caused by bacterial or viral infection, develop dehydration. It becomes life threatening if the lost body fluids are, not replaced. This happens when parents are unable to, recognize the signs., , Aging Effects on Dehydration, Elders are at higher risk for dehydration even if they, are healthy. It is because of increased fluid loss and, decreased fluid intake. In some cases, severe dehydration in old age may be fatal., Treatment, Treatment depends upon the severity of dehydration. In, mild dehydration, the best treatment is drinking of water, and stopping fluid loss. However, in severe dehydration, drinking water alone is ineffective because it cannot, compensate the salt loss. So the effective treatment for, severe dehydration is oral rehydration therapy., Oral rehydration therapy, Oral rehydration therapy (ORT) is the treatment for, dehydration in which a oral rehydration solution (ORS), is administered orally. ORS was formulated by World, Health Organization (WHO). This solution contains, anhydrous glucose, sodium chloride, potassium chloride, and trisodium citrate., In case of very severe dehydration, proper treatment, is the intravenous administration of necessary water and, electrolytes., WATER INTOXICATION OR OVERHYDRATION, Definition, Water intoxication is the condition characterized by great, increase in the water content of the body. It is also called, overhydration, hyperhydration, water excess or water, poisoning., Causes, Water intoxication occurs when more fluid is taken than, that can be excreted. Water intoxication due to drinking, excess water is rare when the body’s systems are, functioning normally. But there are some conditions that, can produce water intoxication., 1. Heart failure in which heart cannot pump blood, properly, 2. Renal disorders in which kidney fails to excrete, enough water in urine, 3. Hypersecretion of antidiuretic hormone as in the, case of syndrome of inappropriate hypersecretion, of antidiuretic hormone (SIADH), 4. Intravenous administration of unduly large amount, of medications and fluids than the person’s body, can excrete
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Chapter 6 t Body Fluids, 5. Infants have greater risk of developing water, intoxication in the first month of life, when the filtration, mechanism of the kidney is underdeveloped and, cannot excrete the fluid rapidly, 6. Water intoxication is also common in children having, swimming practice, since they are more prone to, drink too much of water while swimming, 7. An adult (whose heart and kidneys are functioning, normally) can develop water intoxication, if the, person consumes about 8 L of water everyday, regularly., Signs and Symptoms, 1. Since the brain is more vulnerable to the effects of, water intoxication, behavioral changes appear first, 2. Person becomes drowsy and inattentive, 3. Nausea and vomiting occur, 4. There is sudden loss of weight, followed by weakness and blurred vision, 5. Anemia, acidosis, cyanosis, hemorrhage and shock, are also common, , 57, , 6. Muscular symptoms such as weakness, cramps,, twitching, poor coordination and paralysis develop, 7. Severe conditions of water intoxication result in:, i. Delirium (extreme mental condition characterized, by confused state and illusion), ii. Seizures (sudden uncontrolled involuntary muscular contractions), iii. Coma (profound state of unconsciousness, in, which the person fails to respond to external, stimuli and cannot perform voluntary actions)., Treatment, Mild water intoxication requires only fluid restriction. In, very severe cases, the treatment includes:, 1. Diuretics to increase water loss through urine, 2. Antidiuretic hormone (ADH) receptor antagonists, to prevent ADH-induced reabsorption of water from, renal tubules, 3. Intravenous administration of saline to restore, sodium.
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Chapter, , Blood, , 7, , INTRODUCTION, PROPERTIES, COMPOSITION, , , , , BLOOD CELLS, PLASMA, SERUM, , FUNCTIONS, , , , , , , , , , , NUTRITIVE FUNCTION, RESPIRATORY FUNCTION, EXCRETORY FUNCTION, TRANSPORT OF HORMONES AND ENZYMES, REGULATION OF WATER BALANCE, REGULATION OF ACID-BASE BALANCE, REGULATION OF BODY TEMPERATURE, STORAGE FUNCTION, DEFENSIVE FUNCTION, , INTRODUCTION, Blood is a connective tissue in fluid form. It is considered, as the ‘fluid of life’ because it carries oxygen from lungs, to all parts of the body and carbon dioxide from all parts, of the body to the lungs. It is known as ‘fluid of growth’, because it carries nutritive substances from the digestive, system and hormones from endocrine gland to all the, tissues. The blood is also called the ‘fluid of health’, because it protects the body against the diseases and, gets rid of the waste products and unwanted substances, by transporting them to the excretory organs like, kidneys., , PROPERTIES OF BLOOD, 1. Color: Blood is red in color. Arterial blood is scarlet, red because it contains more oxygen and venous, blood is purple red because of more carbon, dioxide., , 2. Volume: Average volume of blood in a normal adult, is 5 L. In a newborn baby, the volume is 450 ml. It, increases during growth and reaches 5 L at the time, of puberty. In females, it is slightly less and is about, 4.5 L. It is about 8% of the body weight in a normal, young healthy adult, weighing about 70 kg., 3. Reaction and pH: Blood is slightly alkaline and its, pH in normal conditions is 7.4., 4. Specific gravity:, Specific gravity of total blood : 1.052 to 1.061, Specific gravity blood cells : 1.092 to 1.101, Specific gravity of plasma, : 1.022 to 1.026, 5. Viscosity: Blood is five times more viscous than, water. It is mainly due to red blood cells and plasma, proteins., , COMPOSITION OF BLOOD, Blood contains the blood cells which are called formed, elements and the liquid portion known as plasma.
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Chapter 7 t Blood, , FIGURE 7.1: Composition of plasma, , TABLE 7.1: Normal values of some important, substances in blood, , BLOOD CELLS, Three types of cells are present in the blood:, 1. Red blood cells or erythrocytes, 2. White blood cells or leukocytes, 3. Platelets or thrombocytes., Hematocrit Value, If blood is collected in a hematocrit tube along with a, suitable anticoagulant and centrifuged for 30 minutes, at a speed of 3000 revolutions per minute (rpm), the, red blood cells settle down at the bottom having a clear, plasma at the top. Plasma forms 55% and red blood, cells form 45% of the total blood. Volume of red blood, cells expressed in percentage is called the hematocrit, value or packed cell volume (PCV). In between the, plasma and the red blood cells, there is a thin layer of, white buffy coat. This white buffy coat is formed by the, aggregation of white blood cells and platelets (see Fig., 12.1)., , Substance, Glucose, , Normal value, 100 to 120 mg/dL, , Creatinine, , 0.5 to 1.5 mg/dL, , Cholesterol, , Up to 200 mg/dL, , Plasma proteins, , 6.4 to 8.3 g/dL, , Bilirubin, , 0.5 to 1.5 mg/dL, , Iron, Copper, , 50 to 150 µg/dL, 100 to 200 mg/dL, , Calcium, , 9 to 11 mg/dL, 4.5 to 5.5 mEq/L, , Sodium, , 135 to 145 mEq/L, , Potassium, , 3.5 to 5.0 mEq/L, , Magnesium, , 1.5 to 2.0 mEq/L, , Chloride, Bicarbonate, , 100 to 110 mEq/L, 22 to 26 mEq/L, , 59
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60, , Section 2 t Blood and Body Fluids, , PLASMA, Plasma is a straw-colored clear liquid part of blood. It, contains 91% to 92% of water and 8% to 9% of solids., The solids are the organic and the inorganic substances, (Fig. 7.1). Table 7.1 gives the normal values of some, important substances in blood., SERUM, Serum is the clear straw-colored fluid that oozes from, blood clot. When the blood is shed or collected in a, container, it clots. In this process, the fibrinogen is, converted into fibrin and the blood cells are trapped in, this fibrin forming the blood clot. After about 45 minutes,, serum oozes out of the blood clot., For clinical investigations, serum is separated from, blood cells and clotting elements by centrifuging. Volume, of the serum is almost the same as that of plasma, (55%). It is different from plasma only by the absence of, fibrinogen, i.e. serum contains all the other constituents, of plasma except fibrinogen. Fibrinogen is absent in, serum because it is converted into fibrin during blood, clotting. Thus,, Serum = Plasma – Fibrinogen, , to the excretory organs like kidney, skin, liver, etc. for, excretion., 4. TRANSPORT OF HORMONES AND ENZYMES, Hormones which are secreted by ductless (endocrine), glands are released directly into the blood. The blood, transports these hormones to their target organs/tissues., Blood also transports enzymes., 5. REGULATION OF WATER BALANCE, Water content of the blood is freely interchangeable, with interstitial fluid. This helps in the regulation of water, content of the body., 6. REGULATION OF ACID-BASE BALANCE, Plasma proteins and hemoglobin act as buffers and help, in the regulation of acid-base balance (Chapter 5)., 7. REGULATION OF BODY TEMPERATURE, Because of the high specific heat of blood, it is responsible, for maintaining the thermoregulatory mechanism in the, body, i.e. the balance between heat loss and heat gain, in the body., , FUNCTIONS OF BLOOD, , 8. STORAGE FUNCTION, , 1. NUTRITIVE FUNCTION, , Water and some important substances like proteins,, glucose, sodium and potassium are constantly required, by the tissues. Blood serves as a readymade source, for these substances. And, these substances are taken, from blood during the conditions like starvation, fluid, loss, electrolyte loss, etc., , Nutritive substances like glucose, amino acids, lipids and, vitamins derived from digested food are absorbed from, gastrointestinal tract and carried by blood to different, parts of the body for growth and production of energy., 2. RESPIRATORY FUNCTION, Transport of respiratory gases is done by the blood. It, carries oxygen from alveoli of lungs to different tissues, and carbon dioxide from tissues to alveoli., 3. EXCRETORY FUNCTION, Waste products formed in the tissues during various, metabolic activities are removed by blood and carried, , 9. DEFENSIVE FUNCTION, Blood plays an important role in the defense of the, body. The white blood cells are responsible for this, function. Neutrophils and monocytes engulf the, bacteria by phagocytosis. Lymphocytes are involved in, development of immunity. Eosinophils are responsible, for detoxification, disintegration and removal of foreign, proteins (Chapters 16 and 17).
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Chapter, , Plasma Proteins, , , , , , , , , , 8, , INTRODUCTION, NORMAL VALUES, SEPARATION, PROPERTIES, ORIGIN, FUNCTIONS, PLASMAPHERESIS, VARIATIONS IN PLASMA PROTEIN LEVEL, , INTRODUCTION, , SEPARATION OF PLASMA PROTEINS, , Plasma proteins are:, 1. Serum albumin, 2. Serum globulin, 3. Fibrinogen., Serum (Chapter 7) contains only albumin and, globulin. Fibrinogen is absent in serum because, it is, converted into fibrin during blood clotting. Because of, this, the albumin and globulin are usually called serum, albumin and serum globulin., , Plasma proteins are separated by the following, methods., , NORMAL VALUES, Normal values of the plasma proteins are:, Total proteins, : 7.3 g/dL (6.4 to 8.3 g/dL), Serum albumin : 4.7 g/dL, Serum globulin : 2.3 g/dL, Fibrinogen, : 0.3 g/dL, ALBUMIN/GLOBULIN RATIO, Ratio between plasma level of albumin and globulin is, called albumin/globulin (A/G) ratio., It is an important indicator of some diseases involving, liver or kidney., Normal A/G ratio is 2 : 1., , 1. PRECIPITATION METHOD, Proteins in the serum are separated into albumin and, globulin. This is done by precipitating globulin with 22%, sodium sulfate solution. Albumin remains in solution., 2. SALTING-OUT METHOD, Serum globulin is separated into two fractions called, euglobulin and pseudoglobulin by salting out with differ, ent solutions. Euglobulin is salted out by full saturation, with sodium chloride solution; half saturation with, magnesium sulfate solution and onethird saturation, with ammonium sulfate solution. It is insoluble in water., Pseudoglobulin is salted out by full saturation with, magnesium sulfate and, half saturation with ammonium, sulfate. It is soluble in water but it cannot be salted out, by sodium chloride solution., 3. ELECTROPHORETIC METHOD, In this, the plasma proteins are separated depending, on their differences in electrical charge and the rate of, migration. It is done in a Tiselius apparatus by using
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62, , Section 2 t Blood and Body Fluids, , paper or cellulose or starch block. By this method, the, proteins are separated into albumin (55%), alpha globulin, (13%), beta globulin (14%), gamma globulin (11%) and, fibrinogen (7%)., 4. COHN’S FRACTIONAL, PRECIPITATION METHOD, By this method, plasma proteins are separated into, albumin and different fractions of globulin, depending, upon their solubility., 5. ULTRACENTRIFUGATION METHOD, In this method, albumin, globulin and fibrinogen are sep, arated depending upon their density. This method is, also useful in determining the molecular weight of these, proteins., 6. GEL FILTRATION CHROMATOGRAPHY, , BUFFER ACTION, Acceptance of hydrogen ions is called buffer action. The, plasma proteins have 1/6 of total buffering action of the, blood., , ORIGIN OF PLASMA PROTEINS, IN EMBRYO, In embryonic stage, the plasma proteins are synthesized, by the mesenchyme cells. The albumin is synthesized, first and other proteins are synthesized later., IN ADULTS, In adults, the plasma proteins are synthesized mainly, from reticuloendothelial cells of liver. The plasma, proteins are synthesized also from spleen, bone marrow,, disintegrating blood cells and general tissue cells., Gamma globulin is synthesized from B lymphocytes., , Gel filtration chromatography is a column chromatogra, phic method by which the proteins are separated on the, basis of size. Protein molecules are separated by passing, through a bed of porous beads. The diffusion of different, proteins into the beads depends upon their size., , Plasma proteins are very essential for the body. Following, are the functions of plasma proteins:, , 7. IMMUNOELECTROPHORETIC METHOD, , 1. ROLE IN COAGULATION OF BLOOD, , By this method, the proteins are separated on the basis of, electrophoretic patterns formed by precipitation at the site, of antigenantibody reactions. This technique provides, valuable quantitative measurement of different proteins., , Fibrinogen is essential for the coagulation of blood, (Chapter 20)., , PROPERTIES OF PLASMA PROTEINS, MOLECULAR WEIGHT, Albumin, :, 69,000, Globulin, : 1,56,000, Fibrinogen : 4,00,000, Thus, the molecular weight of fibrinogen is greater, than that of other two proteins., ONCOTIC PRESSURE, Plasma proteins are responsible for the oncotic or, osmotic pressure in the blood. Osmotic pressure exerted, by proteins in the plasma is called colloidal osmotic, (oncotic) pressure (Chapter 3). Normally, it is about 25, mm Hg. Albumin plays a major role in exerting oncotic, pressure., SPECIFIC GRAVITY, Specific gravity of the plasma proteins is 1.026., , FUNCTIONS OF PLASMA PROTEINS, , 2. ROLE IN DEFENSE MECHANISM OF BODY, Gamma globulins play an important role in the defense, mechanism of the body by acting as antibodies (immune, substances). These proteins are also called immuno, globulins (Chapter 17). Antibodies react with antigens, of various microorganisms, which cause diseases like, diphtheria, typhoid, streptococcal infections, mumps,, influenza, measles, hepatitis, rubella, poliomyelitis, etc., 3. ROLE IN TRANSPORT MECHANISM, Plasma proteins are essential for the transport of various, substances in the blood. Albumin, alpha globulin and, beta globulin are responsible for the transport of the, hormones, enzymes, etc. The alpha and beta globulins, play an important role in the transport of metals in the, blood., 4. ROLE IN MAINTENANCE OF OSMOTIC, PRESSURE IN BLOOD, At the capillary level, most of the substances are, exchanged between the blood and the tissues. However,
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Chapter 8 t Plasma Proteins, because of their large size, the plasma proteins cannot, pass through the capillary membrane easily and remain, in the blood. In the blood, these proteins exert the, colloidal osmotic (oncotic) pressure. Osmotic pressure, exerted by the plasma proteins is about 25 mm Hg., Since the concentration of albumin is more than the, other plasma proteins, it exerts maximum pressure., Globulin is the next and fibrinogen exerts least pressure., Importance of Osmotic Pressure –, Starling’s Hypothesis, Osmotic pressure exerted by the plasma proteins plays, an important role in the exchange of various substances, between blood and the cells through capillary membrane., According to Starling’s hypothesis, the net filtration, through capillary membrane is proportional to the, hydrostatic pressure difference across the membrane, minus the oncotic pressure difference (Chapter 27)., 5. ROLE IN REGULATION OF, ACID-BASE BALANCE, Plasma proteins, particularly the albumin, play an, important role in regulating the acidbase balance in, the blood. This is because of the virtue of their buffering, action (Chapter 5). Plasma proteins are responsible for, 15% of the buffering capacity of blood., 6. ROLE IN VISCOSITY OF BLOOD, Plasma proteins provide viscosity to the blood, which, is important to maintain the blood pressure. Albumin, provides maximum viscosity than the other plasma, proteins., 7. ROLE IN ERYTHROCYTE, SEDIMENTATION RATE, Globulin and fibrinogen accelerate the tendency of, rouleaux formation by the red blood cells. Rouleaux, formation is responsible for ESR, which is an important, diagnostic and prognostic tool (Chapter 12)., 8. ROLE IN SUSPENSION STABILITY OF, RED BLOOD CELLS, During circulation, the red blood cells remain suspended, uniformly in the blood. This property of the red blood cells, is called the suspension stability. Globulin and fibrinogen, help in the suspension stability of the red blood cells., , 63, , 9. ROLE IN PRODUCTION OF, TREPHONE SUBSTANCES, Trephone substances are necessary for nourishment of, tissue cells in culture. These substances are produced, by leukocytes from the plasma proteins., 10. ROLE AS RESERVE PROTEINS, During fasting, inadequate food intake or inadequate, protein intake, the plasma proteins are utilized by the, body tissues as the last source of energy. Plasma proteins, are split into amino acids by the tissue macrophages., Amino acids are taken back by blood and distributed, throughout the body to form cellular protein molecules., Because of this, the plasma proteins are called the, reserve proteins., , PLASMAPHERESIS, DEFINITION, Plasmapheresis is an experimental procedure done, in animals to demonstrate the importance of plasma, proteins. Earlier, this was called Whipple’s experiment, because it was established by George Hoyt Whipple., PROCEDURE, Plasmapheresis is demonstrated in dogs. Blood is, removed completely from the body of the dog. Red blood, cells are separated from plasma and are washed in, saline and reinfused into the body of the same dog along, with a physiological solution called Locke’s solution., Due to sudden lack of proteins, the animal undergoes, a state of shock. If the animal is fed with diet containing, sufficiently high quantity of proteins, the normal level, of plasma proteins is restored within seven days and, the animal survives. The new plasma proteins are, synthesized by the liver of the dog., If the experiment is done in animals after removal, of liver, even if the diet contains adequate quantity of, proteins, the plasma proteins are not produced. The, shock persists in the animal and leads to death., Thus, the experiment ‘plasmapheresis’ is used to, demonstrate:, 1. Importance of plasma proteins for survival, 2. Synthesis of plasma proteins by the liver., CLINICAL SIGNIFICANCE OF PLASMAPHERESIS, – THERAPEUTIC PLASMA EXCHANGE, Plasmapheresis is used as a blood purification proced, ure for an effective temporary treatment of many auto
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64, , Section 2 t Blood and Body Fluids, TABLE 8.1: Variations in plasma protein level, , Plasma Protein, , Total proteins, , Albumin, , Conditions when increases, , Conditions when decreases, , Hyperproteinemia:, 1. Dehydration, 2. Hemolysis, 3. Acute infections like acute hepatitis and, acute nephritis, 4. Respiratory distress syndrome, 5. Excess of glucocorticoids, 6. Leukemia, 7. Rheumatoid arthritis, 8. Alcoholism, , Hypoproteinemia:, 1. Diarrhea, 2. Hemorrhage, 3. Burns, 4. Pregnancy, 5. Malnutrition, 6. Prolonged starvation, 7. Cirrhosis of liver, 8. Chronic infections like chronic hepatitis or, chronic nephritis, 1. Malnutrition, 2. Cirrhosis of liver, 3. Burns, 4. Hypothyroidism, 5. Nephrosis, 6. Excessive intake of water, , 1. Dehydration, 2. Excess of glucocorticoids, 3. Congestive cardiac failure, , Globulin, , 1. Cirrhosis of liver, 2. Chronic infections, 3. Nephrosis, 4. Rheumatoid arthritis, , 1. Emphysema, 2. Acute hemolytic anemia, 3. Glomerulonephritis, 4. Hypogammaglobulinemia, , Fibrinogen, , 1. Acute infections, 2. Rheumatoid arthritis, 3. Glomerulonephritis, 4. Myocardial infarction, 5. Stroke, 6. Trauma, , 1. Liver dysfunction, 2. Use of anabolic steroids, 3. Use of phenobarbital, , A/G ratio, , 1. Hypothyroidism, 2. Excess of glucocorticoids, 3. Hypogammaglobulinemia, 4. Intake of high carbohydrate or protein diet, , 1. Liver dysfunction, 2. Nephrosis, , immune diseases. It is also called therapeutic plasma, exchange., In an autoimmune disease, the immune system, attacks the body’s own tissues through antibodies, (Chapter 17). The antibodies that are proteins in nature, circulate in the bloodstream before attacking the target, tissues. Plasmapheresis is used to remove these, antibodies from the blood., Procedure, Venous blood is removed from the patient and blood, cells are separated from plasma by the equipment called, cell separator. This equipment works on the principle of, a centrifuge. An anticoagulant is used to prevent the, clotting of blood when it is removed from the body. After, the separation of blood cells, the plasma is discarded., The blood cells are returned to the bloodstream of the, , patient by mixing with a substitute fluid (saline) and, sterilized human albumin protein., Uses of Plasmapheresis, Though plasmapheresis is used to remove antibodies, from the blood, it cannot prevent the production of, antibodies by the immune system of the body. So, it can, provide only a temporary benefit of protecting the tissues, from the antibodies. The patients must go for repeated, sessions of this treatment., Plasmapheresis is an effective temporary treatment, for the following diseases:, 1. Myasthenia gravis – autoimmune disease causing, muscle weakness (Chapter 17), 2. Thrombocytopenic purpura – bleeding disorder, (Chapter 20)
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Chapter 8 t Plasma Proteins, 3. Paraproteinemic peripheral neuropathy – dysfunc, tion of peripheral nervous system due to an, abnormal immunoglobulin called paraprotein., 4. Chronic demyelinating polyneuropathy – neurolo, gical disorder characterized by progressive weak, ness and impaired sensory function in the legs, and arms due to the damage of myelin sheath in, peripheral nerves., 5. GuillainBarré syndrome – autoimmune disease, causing weakness, abnormal sensations (like, tingling) in the limbs and paralysis., , 65, , 6. LambertEaton myasthenic syndrome – autoim, mune disorder of the neuromuscular junction., , VARIATIONS IN PLASMA PROTEIN LEVEL, Level of plasma proteins vary independently of one, another. However, in several conditions, the quantity, of albumin and globulin change in opposite direction., Elevation of all fractions of plasma proteins is called, hyperproteinemia and decrease in all fractions of, plasma proteins is called hypoproteinemia. Variations, in the level of plasma proteins are given in Table 8.1.
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Chapter, , Red Blood Cells, , , , , , , , , , , , , 9, , INTRODUCTION, NORMAL VALUE, MORPHOLOGY, PROPERTIES, LIFESPAN, FATE, FUNCTIONS, VARIATIONS IN NUMBER, VARIATIONS IN SIZE, VARIATIONS IN SHAPE, VARIATIONS IN STRUCTURE, , INTRODUCTION, Red blood cells (RBCs) are the non-nucleated formed, elements in the blood. Red blood cells are also known, as erythrocytes (erythros = red). Red color of the red, blood cell is due to the presence of the coloring pigment, called hemoglobin. RBCs play a vital role in transport of, respiratory gases. RBCs are larger in number compared, to the other two blood cells, namely white blood cells, and platelets., , NORMAL VALUE, RBC count ranges between 4 and 5.5 million/cu mm of, blood. In adult males, it is 5 million/cu mm and in adult, females, it is 4.5 million/cu mm., , MORPHOLOGY OF RED BLOOD CELLS, NORMAL SHAPE, Normally, the RBCs are disk shaped and biconcave, (dumbbell shaped). Central portion is thinner and peri, phery is thicker. The biconcave contour of RBCs has, some mechanical and functional advantages., , Advantages of Biconcave Shape of RBCs, 1. Biconcave shape helps in equal and rapid diffusion, of oxygen and other substances into the interior of, the cell., 2. Large surface area is provided for absorption or, removal of different substances., 3. Minimal tension is offered on the membrane when, the volume of cell alters., 4. Because of biconcave shape, while passing through, minute capillaries, RBCs squeeze through the capill, aries very easily without getting damaged., NORMAL SIZE, Diameter, Thickness, , : 7.2 µ (6.9 to 7.4 µ)., : At the periphery it is thicker with 2.2 µ, and at the center it is thinner with 1 µ, (Fig. 9.1). This difference in thickness is, because of the biconcave shape., Surface area : 120 sq µ., Volume, : 85 to 90 cu µ., NORMAL STRUCTURE, Red blood cells are nonnucleated. Only mammal,, which has nucleated RBC is camel. Because of the
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Chapter 9 t Red Blood Cells, , 67, , FIGURE 9.1: Dimensions of RBC., A. Surface view, B. Sectioned view., FIGURE 9.2: Rouleau formation, (Courtesy: Dr Nivaldo Medeiros), , absence of nucleus in human RBC, the DNA is also, absent. Other organelles such as mitochondria and Golgi, apparatus also are absent in RBC. Because of absence, of mitochondria, the energy is produced from glycolytic, process. Red cell does not have insulin receptor and, so the glucose uptake by this cell is not controlled by, insulin., RBC has a special type of cytoskeleton, which is made, up of actin and spectrin. Both the proteins are anchored, to transmembrane proteins by means of another protein, called ankyrin. Absence of spectrin results in hereditary, spherocytosis. In this condition, the cell is deformed,, losses its biconcave shape and becomes globular, (spherocytic). The spherocyte is very fragile and easily, ruptured (hemolyzed) in hypotonic solutions., , PROPERTIES OF RED BLOOD CELLS, ROULEAUX FORMATION, When blood is taken out of the blood vessel, the RBCs, pile up one above another like the pile of coins. This, property of the RBCs is called rouleaux (pleural =, rouleau) formation (Fig. 9.2). It is accelerated by plasma, proteins globulin and fibrinogen., SPECIFIC GRAVITY, Specific gravity of RBC is 1.092 to 1.101., PACKED CELL VOLUME, Packed cell volume (PCV) is the proportion of blood, occupied by RBCs expressed in percentage. It is also, called hematocrit value. It is 45% of the blood and the, plasma volume is 55% (Chapters 7 and 13)., , SUSPENSION STABILITY, During circulation, the RBCs remain suspended uniformly, in the blood. This property of the RBCs is called the, suspension stability., , LIFESPAN OF RED BLOOD CELLS, Average lifespan of RBC is about 120 days. After, the lifetime the senile (old) RBCs are destroyed in, reticuloendothelial system., Determination of Lifespan of Red Blood Cells, Lifespan of the RBC is determined by radioisotope, method. RBCs are tagged with radioactive substances, like radioactive iron or radioactive chromium. Life of, RBC is determined by studying the rate of loss of radio, active cells from circulation., , FATE OF RED BLOOD CELLS, When the cells become older (120 days), the cell, membrane becomes more fragile. Diameter of the, capillaries is less or equal to that of RBC. Younger RBCs, can pass through the capillaries easily. However, because, of the fragile nature, the older cells are destroyed while, trying to squeeze through the capillaries. The destruction, occurs mainly in the capillaries of red pulp of spleen, because the diameter of splenic capillaries is very small., So, the spleen is called ‘graveyard of RBCs’., Destroyed RBCs are fragmented and hemoglobin, is released from the fragmented parts. Hemoglobin is, immediately phagocytized by macrophages of the body,, particularly the macrophages present in liver (Kupffer, cells), spleen and bone marrow.
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68, , Section 2 t Blood and Body Fluids, , Hemoglobin is degraded into iron, globin and, porphyrin. Iron combines with the protein called, apoferritin to form ferritin, which is stored in the body and, reused later. Globin enters the protein depot for later use, (Fig. 9.3). Porphyrin is degraded into bilirubin, which is, excreted by liver through bile (Chapter 40)., Daily 10% RBCs, which are senile, are destroyed in, normal young healthy adults. It causes release of about, 0.6 g/dL of hemoglobin into the plasma. From this 0.9 to, 1.5 mg/dL bilirubin is formed., , FUNCTIONS OF RED BLOOD CELLS, Major function of RBCs is the transport of respiratory, gases. Following are the functions of RBCs:, 1. Transport of Oxygen from the Lungs to the, Tissues, Hemoglobin in RBC combines with oxygen to form, oxyhemoglobin. About 97% of oxygen is transported in, blood in the form of oxyhemoglobin (Chapter 125)., 2. Transport of Carbon Dioxide from the Tissues, to the Lungs, Hemoglobin combines with carbon dioxide and form, carbhemoglobin. About 30% of carbon dioxide is trans, ported in this form., , RBCs contain a large amount of the carbonic, anhydrase. This enzyme is necessary for the formation, of bicarbonate from water and carbon dioxide (Chapter, 125). Thus, it helps to transport carbon dioxide in the, form of bicarbonate from tissues to lungs. About 63% of, carbon dioxide is transported in this form., 3. Buffering Action in Blood, Hemoglobin functions as a good buffer. By this action,, it regulates the hydrogen ion concentration and thereby, plays a role in the maintenance of acidbase balance, (Chapter 5)., 4. In Blood Group Determination, RBCs carry the blood group antigens like A antigen,, B antigen and Rh factor. This helps in determination of, blood group and enables to prevent reactions due to, incompatible blood transfusion (Chapter 21)., , VARIATIONS IN NUMBER OF RED, BLOOD CELLS, PHYSIOLOGICAL VARIATIONS, A. Increase in RBC Count, Increase in the RBC count is known as polycythemia. It, occurs in both physiological and pathological conditions., When it occurs in physiological conditions it is called, physiological polycythemia. The increase in number, during this condition is marginal and temporary. It occurs, in the following conditions:, 1. Age, At birth, the RBC count is 8 to 10 million/cu mm of blood., The count decreases within 10 days after birth due to, destruction of RBCs causing physiological jaundice in, some newborn babies. However, in infants and growing, children, the cell count is more than the value in adults., 2. Sex, Before puberty and after menopause in females the RBC, count is similar to that in males. During reproductive, period of females, the count is less than that of males, (4.5 million/cu mm)., 3. High altitude, , FIGURE 9.3: Fate of RBC, , Inhabitants of mountains (above 10,000 feet from mean, sea level) have an increased RBC count of more than 7, million/cu mm. It is due to hypoxia (decreased oxygen, supply to tissues) in high altitude. Hypoxia stimulates, kidney to secrete a hormone called erythropoietin. The
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Chapter 9 t Red Blood Cells, , 69, , erythropoietin in turn stimulates the bone marrow to, produce more RBCs (Fig. 9.4)., 4. Muscular exercise, There is a temporary increase in RBC count after, exercise. It is because of mild hypoxia and contraction, of spleen. Spleen stores RBCs (Chapter 25). Hypoxia, increases the sympathetic activity resulting in secretion, of adrenaline from adrenal medulla. Adrenaline contracts, spleen and RBCs are released into blood (Fig. 9.5)., 5. Emotional conditions, RBC count increases during the emotional conditions, such as anxiety. It is because of increase in the sympathe, tic activity as in the case of muscular exercise (Fig. 9.5)., 6. Increased environmental temperature, Increase in atmospheric temperature increases RBC, count. Generally increased temperature increases all, the activities in the body including production of RBCs., 7. After meals, There is a slight increase in the RBC count after taking, meals. It is because of need for more oxygen for, metabolic activities., , FIGURE 9.5: Physiological polycythemia in emotional, conditions and exercise, , B. Decrease in RBC Count, Decrease in RBC count occurs in the following physiolo, gical conditions:, 1. High barometric pressures, At high barometric pressures as in deep sea, when, the oxygen tension of blood is higher, the RBC count, decreases., 2. During sleep, RBC count decreases slightly during sleep and imme, diately after getting up from sleep. Generally all the, activities of the body are decreased during sleep includ, ing production of RBCs., 3. Pregnancy, In pregnancy, the RBC count decreases. It is because, of increase in ECF volume. Increase in ECF volume,, increases the plasma volume also resulting in hemodilu, tion. So, there is a relative reduction in the RBC count., PATHOLOGICAL VARIATIONS, Pathological Polycythemia, , FIGURE 9.4: Physiological polycythemia in high altitude, , Pathological polycythemia is the abnormal increase in, the RBC count. Red cell count increases above 7 million/, cu mm of the blood. Polycythemia is of two types, the, primary polycythemia and secondary polycythemia.
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70, , Section 2 t Blood and Body Fluids, , Primary Polycythemia – Polycythemia Vera, , MACROCYTES, , Primary polycythemia is otherwise known as polycythemia, vera. It is a disease characterized by persistent increase, in RBC count above 14 million/cu mm of blood. This, is always associated with increased white blood cell, count above 24,000/cu mm of blood. Polycythemia vera, occurs in myeloproliferative disorders like malignancy, of red bone marrow., , Macrocytes are present in:, i. Megaloblastic anemia, ii. Decreased osmotic pressure in blood., , Secondary Polycythemia, , VARIATIONS IN SHAPE OF RED, BLOOD CELLS, , This is secondary to some of the pathological conditions, (diseases) such as:, 1. Respiratory disorders like emphysema., 2. Congenital heart disease., 3. Ayerza’s disease (condition associated with, hypertrophy of right ventricle and obstruction of, blood flow to lungs)., 4. Chronic carbon monoxide poisoning., 5. Poisoning by chemicals like phosphorus and, arsenic., 6. Repeated mild hemorrhages., All these conditions lead to hypoxia which stimulates, the release of erythropoietin. Erythropoietin stimulates, the bone marrow resulting in increased RBC count., Anemia, Abnormal decrease in RBC count is called anemia. This, is described in Chapter 14., , ANISOCYTES, Anisocytes occurs in pernicious anemia., , Shape of RBCs is altered in many conditions including, different types of anemia., 1. Crenation: Shrinkage as in hypertonic conditions., 2. Spherocytosis: Globular form as in hypotonic, conditions., 3. Elliptocytosis: Elliptical shape as in certain types of, anemia., 4. Sickle cell: Crescentic shape as in sickle cell, anemia., 5. Poikilocytosis: Unusual shapes due to deformed, cell membrane. The shape will be of flask, hammer, or any other unusual shape., , VARIATIONS IN STRUCTURE OF, RED BLOOD CELLS, PUNCTATE BASOPHILISM, , VARIATIONS IN SIZE OF RED, BLOOD CELLS, Under physiological conditions, the size of RBCs in, venous blood is slightly larger than those in arterial, blood. In pathological conditions, the variations in size, of RBCs are:, 1. Microcytes (smaller cells), 2. Macrocytes (larger cells), 3. Anisocytes (cells with different sizes)., MICROCYTES, Microcytes are present in:, i. Iron-deficiency anemia, ii. Prolonged forced breathing, iii. Increased osmotic pressure in blood., , Striated appearance of RBCs by the presence of dots, of basophilic materials (porphyrin) is called punctate, basophilism. It occurs in conditions like lead poisoning., RING IN RED BLOOD CELLS, Ring or twisted strands of basophilic material appear, in the periphery of the RBCs. This is also called the, Goblet ring. This appears in the RBCs in certain types, of anemia., HOWELL-JOLLY BODIES, In certain types of anemia, some nuclear fragments are, present in the ectoplasm of the RBCs. These nuclear, fragments are called HowellJolly bodies.
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Chapter, , Erythropoiesis, , 10, , DEFINITION, SITE OF ERYTHROPOIESIS, , , , IN FETAL LIFE, IN NEWBORN BABIES, CHILDREN AND ADULTS, , PROCESS OF ERYTHROPOIESIS, , , , , STEM CELLS, CHANGES DURING ERYTHROPOIESIS, STAGES OF ERYTHROPOIESIS, , FACTORS NECESSARY FOR ERYTHROPOIESIS, , , , , GENERAL FACTORS, MATURATION FACTORS, FACTORS NECESSARY FOR HEMOGLOBIN FORMATION, , DEFINITION, , IN NEWBORN BABIES, CHILDREN AND ADULTS, , Erythropoiesis is the process of the origin, development, and maturation of erythrocytes. Hemopoiesis or hema, topoiesis is the process of origin, development and, maturation of all the blood cells., , In newborn babies, growing children and adults, RBCs, are produced only from the red bone marrow., 1. Up to the age of 20 years: RBCs are produced from, red bone marrow of all bones (long bones and all, the flat bones)., 2. After the age of 20 years: RBCs are produced, from membranous bones like vertebra, sternum,, ribs, scapula, iliac bones and skull bones and from, the ends of long bones. After 20 years of age,, the shaft of the long bones becomes yellow bone, marrow because of fat deposition and looses the, erythropoietic function., In adults, liver and spleen may produce the blood cells, if the bone marrow is destroyed or fibrosed. Collectively, bone marrow is almost equal to liver in size and weight., It is also as active as liver. Though bone marrow is the, site of production of all blood cells, comparatively 75%, of the bone marrow is involved in the production of, leukocytes and only 25% is involved in the production, of erythrocytes., But still, the leukocytes are less in number than the, erythrocytes, the ratio being 1:500. This is mainly because, of the lifespan of these cells. Lifespan of erythrocytes, is 120 days whereas the lifespan of leukocytes is very, , SITE OF ERYTHROPOIESIS, IN FETAL LIFE, In fetal life, the erythropoiesis occurs in three stages:, 1. Mesoblastic Stage, During the first two months of intrauterine life, the RBCs, are produced from mesenchyme of yolk sac., 2. Hepatic Stage, From third month of intrauterine life, liver is the main, organ that produces RBCs. Spleen and lymphoid, organs are also involved in erythropoiesis., 3. Myeloid Stage, During the last three months of intrauterine life, the RBCs, are produced from red bone marrow and liver.
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72, , Section 2 t Blood and Body Fluids, , short ranging from one to ten days. So the leukocytes, need larger production than erythrocytes to maintain the, required number., , PROCESS OF ERYTHROPOIESIS, STEM CELLS, Stem cells are the primary cells capable of self-renewal, and differentiating into specialized cells (Chapter 1)., Hemopoietic stem cells are the primitive cells in the, bone marrow, which give rise to the blood cells., Hemopoietic stem cells in the bone marrow are called, uncommitted pluripotent hemopoietic stem cells (PHSC)., PHSC is defined as a cell that can give rise to all types of, blood cells. In early stages, the PHSC are not designed, to form a particular type of blood cell. And it is also not, possible to determine the blood cell to be developed, from these cells: hence, the name uncommitted PHSC, (Fig. 10.1). In adults, only a few number of these cells, are present. But the best source of these cells is the, umbilical cord blood., When the cells are designed to form a particular, type of blood cell, the uncommitted PHSCs are called, committed PHSCs. Committed PHSC is defined as a, cell, which is restricted to give rise to one group of blood, cells., , Committed PHSCs are of two types:, 1. Lymphoid stem cells (LSC) which give rise to, lymphocytes and natural killer (NK) cells, 2. Colony forming blastocytes, which give rise to, myeloid cells. Myeloid cells are the blood cells other, than lymphocytes. When grown in cultures, these, cells form colonies hence the name colony forming, blastocytes., Different units of colony forming cells are:, i. Colony forming unit-erythrocytes (CFU-E) –, Cells of this unit develop into erythrocytes, ii. Colony forming unit-granulocytes/monocytes, (CFU-GM) – These cells give rise to granulocytes, (neutrophils, basophils and eosinophils) and, monocytes, iii. Colony forming unit-megakaryocytes (CFU-M), – Platelets are developed from these cells., CHANGES DURING ERYTHROPOIESIS, Cells of CFU-E pass through different stages and finally, become the matured RBCs. During these stages four, important changes are noticed., 1. Reduction in size of the cell (from the diameter of 25, to 7.2 µ), 2. Disappearance of nucleoli and nucleus, , FIGURE 10.1: Stem cells. L = Lymphocyte, R = Red blood cell, N = Neutrophil, B = Basophil,, E = Eosinophil, M = Monocyte, P = Platelet.
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Chapter 10 t Erythropoiesis, 3. Appearance of hemoglobin, 4. Change in the staining properties of the cytoplasm., , 73, , 4. Late normoblast, 5. Reticulocyte, 6. Matured erythrocyte., , STAGES OF ERYTHROPOIESIS, Various stages between CFU-E cells and matured RBCs, are (Fig. 10.2):, 1. Proerythroblast, 2. Early normoblast, 3. Intermediate normoblast., , 1. Proerythroblast (Megaloblast), Proerythroblast or megaloblast is the first cell derived, from CFU-E. It is very large in size with a diameter of, about 20 µ. Its nucleus is large and occupies the cell, almost completely. The nucleus has two or more nucleoli, , FIGURE 10.2: Stages of erythropoiesis. CFU-E = Colony forming unit-erythrocyte,, CFU-M = Colony forming unit-megakaryocyte, CFU-GM = Colony forming unit-granulocyte/monocyte.
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74, , Section 2 t Blood and Body Fluids, , and a reticular network. Proerythroblast does not contain, hemoglobin. The cytoplasm is basophilic in nature., Proerythroblast multiplies several times and finally forms, the cell of next stage called early normoblast. Synthesis, of hemoglobin starts in this stage. However, appearance, of hemoglobin occurs only in intermediate normoblast., 2. Early Normoblast, The early normoblast is little smaller than proerythroblast, with a diameter of about 15 µ. In the nucleus, the, nucleoli disappear. Condensation of chromatin network, occurs. The condensed network becomes dense. The, cytoplasm is basophilic in nature. So, this cell is also, called basophilic erythroblast. This cell develops into, next stage called intermediate normoblast., 3. Intermediate Normoblast, Cell is smaller than the early normoblast with a diameter, of 10 to 12 µ. The nucleus is still present. But, the, chromatin network shows further condensation. The, hemoglobin starts appearing., Cytoplasm is already basophilic. Now, because of the, presence of hemoglobin, it stains with both acidic as well, as basic stains. So this cell is called polychromophilic or, polychromatic erythroblast. This cell develops into next, stage called late normoblast., 4. Late Normoblast, Diameter of the cell decreases further to about 8 to 10 µ., Nucleus becomes very small with very much condensed, chromatin network and it is known as ink-spot nucleus., Quantity of hemoglobin increases. And the cyto, plasm becomes almost acidophilic. So, the cell is now, called orthochromic erythroblast. In the final stage of, late normoblast just before it passes to next stage, the, nucleus disintegrates and disappears. The process by, which nucleus disappears is called pyknosis. The final, remnant is extruded from the cell. Late normoblast, develops into the next stage called reticulocyte., 5. Reticulocyte, Reticulocyte is otherwise known as immature RBC., It is slightly larger than matured RBC. The cytoplasm, contains the reticular network or reticulum, which is, formed by remnants of disintegrated organelles. Due to, the reticular network, the cell is called reticulocyte. The, reticulum of reticulocyte stains with supravital stain., In newborn babies, the reticulocyte count is 2% to, 6% of RBCs, i.e. 2 to 6 reticulocytes are present for, every 100 RBCs. The number of reticulocytes decreases, , during the first week after birth. Later, the reticulocyte, count remains constant at or below 1% of RBCs. The, number increases whenever production and release of, RBCs increase., Reticulocyte is basophilic due to the presence of, remnants of disintegrated Golgi apparatus, mitochondria, and other organelles of cytoplasm. During this stage, the, cells enter the blood capillaries through capillary mem, brane from site of production by diapedesis. Important, events during erythropoiesis is given in Table 10.1, 6. Matured Erythrocyte, Reticular network disappears and the cell becomes the, matured RBC and attains the biconcave shape. The cell, decreases in size to 7.2 µ diameter. The matured RBC, is with hemoglobin but without nucleus., It requires 7 days for the development and maturation, of RBC from proerythroblast. It requires 5 days up to the, stage of reticulocyte. Reticulocyte takes 2 more days to, become the matured RBC., TABLE 10.1: Important events during erythropoiesis, Stage of erythropoiesis, , Important event, , Proerythroblast, , Synthesis of hemoglobin starts, , Early normoblast, , Nucleoli disappear, , Intermediate normoblast, , Hemoglobin starts appearing, , Late normoblast, , Nucleus disappears, , Reticulocyte, , Reticulum is formed., Cell enters capillary from site of, production, , Matured RBC, , Reticulum disappears, Cell attains biconcavity, , FACTORS NECESSARY FOR, ERYTHROPOIESIS, Development and maturation of erythrocytes require variety of factors, which are classified into three categories:, 1. General factors, 2. Maturation factors, 3. Factors necessary for hemoglobin formation., GENERAL FACTORS, General factors necessary for erythropoiesis are:, i. Erythropoietin, ii. Thyroxine, iii. Hemopoietic growth factors, iv. Vitamins.
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Chapter 10 t Erythropoiesis, , 75, , i. Erythropoietin, , iv. Vitamins, , Most important general factor for erythropoiesis is, the hormone called erythropoietin. It is also called, hemopoietin or erythrocyte stimulating factor., , Some vitamins are also necessary for the process of, erythropoiesis. Deficiency of these vitamins cause, anemia associated with other disorders., Vitamins necessary for erythropoiesis:, a. Vitamin B: Its deficiency causes anemia and, pellagra (disease characterized by skin lesions,, diarrhea, weakness, nervousness and dementia)., b. Vitamin C: Its deficiency causes anemia, and scurvy (ancient disease characterized, by impaired collagen synthesis resulting in, rough skin, bleeding gum, loosening of teeth,, poor wound healing, bone pain, lethargy and, emotional changes)., c. Vitamin D: Its deficiency causes anemia and, rickets (bone disease – Chapter 68)., d. Vitamin E: Its deficiency leads to anemia and, malnutrition., , Chemistry, Erythropoietin is a glycoprotein with 165 amino acids., Source of secretion, Major quantity of erythropoietin is secreted by peritubular, capillaries of kidney. A small quantity is also secreted, from liver and brain., Stimulant for secretion, Hypoxia is the, erythropoietin., , stimulant, , for, , the, , secretion, , of, , Actions of erythropoietin, Erythropoietin causes formation and release of new, RBCs into circulation. After secretion, it takes 4 to 5 days, to show the action., Erythropoietin promotes the following processes:, a. Production of proerythroblasts from CFU-E of, the bone marrow, b. Development of proerythroblasts into matured, RBCs through the several stages – early normoblast, intermediate normoblast, late normoblast, and reticulocyte, c. Release of matured erythrocytes into blood. Even, some reticulocytes (immature erythrocytes) are, released along with matured RBCs., Blood level of erythropoietin increases in anemia., ii. Thyroxine, Being a general metabolic hormone, thyroxine, accelerates the process of erythropoiesis at many levels., So, hyperthyroidism and polycythemia are common., iii. Hemopoietic Growth Factors, Hemopoietic growth factors or growth inducers are the, interleukins and stem cell factor (steel factor). Generally, these factors induce the proliferation of PHSCs., Interleukins (IL) are glycoproteins, which belong to the, cytokines family., Interleukins involved in erythropoiesis:, a. Interleukin-3 (IL-3) secreted by T-cells, b. Interleukin-6 (IL-6) secreted by T-cells, endothelial, cells and macrophages, c. Interleukin-11 (IL-11) secreted by osteoblast., , MATURATION FACTORS, Vitamin B12, intrinsic factor and folic acid are necessary, for the maturation of RBCs., 1. Vitamin B12 (Cyanocobalamin), Vitamin B12 is the maturation factor necessary for, erythropoiesis., Source, Vitamin B12 is called extrinsic factor since it is obtained, mostly from diet. Its absorption from intestine requires, the presence of intrinsic factor of Castle. Vitamin B12, is stored mostly in liver and in small quantity in muscle., When necessary, it is transported to the bone marrow to, promote maturation of RBCs. It is also produced in the, large intestine by the intestinal flora., Action, Vitamin B12 is essential for synthesis of DNA in RBCs., Its deficiency leads to failure in maturation of the cell, and reduction in the cell division. Also, the cells are, larger with fragile and weak cell membrane resulting in, macrocytic anemia., Deficiency of vitamin B12 causes pernicious anemia., So, vitamin B12 is called antipernicious factor., 2. Intrinsic Factor of Castle, Intrinsic factor of castle is produced in gastric mucosa, by the parietal cells of the gastric glands. It is essential
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76, , Section 2 t Blood and Body Fluids, , for the absorption of vitamin B12 from intestine. In the, absence of intrinsic factor, vitamin B12 is not absorbed, from intestine. This leads to pernicious anemia., Deficiency of intrinsic factor occurs in:, i. Severe gastritis, ii. Ulcer, iii. Gastrectomy., Hematinic principle, Hematinic principle is the principle thought to be, produced by the action of intrinsic factor on extrinsic, factor. It is also called or antianemia principle. It is a, maturation factor., 3. Folic Acid, Folic acid is also essential for maturation. It is required, for the synthesis of DNA. In the absence of folic acid,, the synthesis of DNA decreases causing failure of, maturation. This leads to anemia in which the cells are, larger and appear in megaloblastic (proerythroblastic), stage. And, anemia due to folic acid deficiency is called, megaloblastic anemia., , FACTORS NECESSARY FOR, HEMOGLOBIN FORMATION, Various materials are essential for the formation of hemo, globin in the RBCs. Deficiency of these substances decreases the production of hemoglobin leading to anemia., Such factors are:, 1. First class proteins and amino acids: Proteins of, high biological value are essential for the formation, of hemoglobin. Amino acids derived from these, proteins are required for the synthesis of protein, part of hemoglobin, i.e. the globin., 2. Iron: Necessary for the formation of heme part of, the hemoglobin., 3. Copper: Necessary for the absorption of iron from, the gastrointestinal tract., 4. Cobalt and nickel: These metals are essential for, the utilization of iron during hemoglobin formation., 5. Vitamins: Vitamin C, riboflavin, nicotinic acid and, pyridoxine are also essential for the formation of, hemoglobin.
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Chapter, , Hemoglobin and, Iron Metabolism, , , , , , , , , , , , 11, , INTRODUCTION, NORMAL HEMOGLOBIN CONTENT, FUNCTIONS, STRUCTURE, TYPES OF NORMAL HEMOGLOBIN, ABNORMAL HEMOGLOBIN, ABNORMAL HEMOGLOBIN DERIVATIVES, SYNTHESIS, DESTRUCTION, IRON METABOLISM, , INTRODUCTION, , FUNCTIONS OF HEMOGLOBIN, , Hemoglobin (Hb) is the iron containing coloring matter of, red blood cell (RBC). It is a chromoprotein forming 95%, of dry weight of RBC and 30% to 34% of wet weight., Function of hemoglobin is to carry the respiratory gases,, oxygen and carbon dioxide. It also acts as a buffer., Molecular weight of hemoglobin is 68,000., , TRANSPORT OF RESPIRATORY GASES, , NORMAL HEMOGLOBIN CONTENT, , 1. Transport of Oxygen, , Average hemoglobin (Hb) content in blood is 14 to 16 g/dL., However, the value varies depending upon the age and, sex of the individual., Age, At birth, : 25 g/dL, After 3rd month, : 20 g/dL, After 1 year, : 17 g/dL, From puberty onwards : 14 to 16 g/dL, At the time of birth, hemoglobin content is very high, because of increased number of RBCs (Chapter 9)., Sex, In adult males, In adult females, , : 15 g/dL, : 14.5 g/dL, , Main function of hemoglobin is the transport of respiratory, gases:, 1. Oxygen from the lungs to tissues., 2. Carbon dioxide from tissues to lungs., , When oxygen binds with hemoglobin, a physical process, called oxygenation occurs, resulting in the formation of, oxyhemoglobin. The iron remains in ferrous state in this, compound. Oxyhemoglobin is an unstable compound, and the combination is reversible, i.e. when more oxygen, is available, it combines with hemoglobin and whenever, oxygen is required, hemoglobin can release oxygen, readily (Chapter 125)., When oxygen is released from oxyhemoglobin, it is, called reduced hemoglobin or ferrohemoglobin., 2. Transport of Carbon Dioxide, When carbon dioxide binds with hemoglobin, carbhe, moglobin is formed. It is also an unstable compound, and the combination is reversible, i.e. the carbon dioxide, can be released from this compound. The affinity of
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78, , Section 2 t Blood and Body Fluids, , hemoglobin for carbon dioxide is 20 times more than, that for oxygen (Chapter 125)., , to 12th week after birth. Both the types of hemoglobin, differ from each other structurally and functionally., , BUFFER ACTION, , Structural Difference, , Hemoglobin acts as a buffer and plays an important role, in acidbase balance (Chapter 5)., , In adult hemoglobin, the globin contains two α-chains, and two β-chains. In fetal hemoglobin, there are two α, chains and two γ-chains instead of β-chains., , STRUCTURE OF HEMOGLOBIN, Hemoglobin is a conjugated protein. It consists of a, protein combined with an ironcontaining pigment. The, protein part is globin and the ironcontaining pigment, is heme. Heme also forms a part of the structure of, myoglobin (oxygenbinding pigment in muscles) and, neuroglobin (oxygenbinding pigment in brain)., , Functionally, fetal hemoglobin has more affinity for, oxygen than that of adult hemoglobin. And, the oxygen, hemoglobin dissociation curve of fetal blood is shifted to, left (Chapter 125)., , ABNORMAL HEMOGLOBIN, , IRON, Normally, it is present in ferrous (Fe2+) form. It is in, unstable or loose form. In some abnormal conditions,, the iron is converted into ferric (Fe3+) state, which is a, stable form., PORPHYRIN, The pigment part of heme is called porphyrin. It is, formed by four pyrrole rings (tetrapyrrole) called, I, II, III, and IV. The pyrrole rings are attached to one another by, methane (CH4) bridges., The iron is attached to ‘N’ of each pyrrole ring and ‘N’, of globin molecule., GLOBIN, Globin contains four polypeptide chains. Among the four, polypeptide chains, two are chains and two are α-chains, (Refer Table 11.1 for molecular weight and number of, amino acids in the polypeptide chains)., TABLE 11.1: Molecular weight and number of amino, acids of polypeptide chains of globin, Molecular, weight, , Amino acids, , α-chain, , 15,126, , 141, , β-chain, , 15,866, , 146, , Polypeptide chain, , Functional Difference, , TYPES OF NORMAL HEMOGLOBIN, Hemoglobin is of two types:, 1. Adult hemoglobin – HbA, 2. Fetal hemoglobin – HbF, Replacement of fetal hemoglobin by adult hemoglobin, starts immediately after birth. It is completed at about 10th, , Abnormal types of hemoglobin or hemoglobin variants, are the pathologic mutant forms of hemoglobin. These, variants are produced because of structural changes, in the polypeptide chains caused by mutation in the, genes of the globin chains. Most of the mutations do not, produce any serious problem. Occasionally, few muta, tions result in some disorders., There are two categories of abnormal hemoglobin:, 1. Hemoglobinopathies, 2. Hemoglobin in thalassemia and related disorders., 1. Hemoglobinopathies, Hemoglobinopathy is a genetic disorder caused by, abnormal polypeptide chains of hemoglobin., Some of the hemoglobinopathies are:, i. Hemoglobin S: It is found in sickle cell anemia., In this, the α-chains are normal and β-chains are, abnormal., ii. Hemoglobin C: The β-chains are abnormal. It is, found in people with hemoglobin C disease, which, is characterized by mild hemolytic anemia and, splenomegaly., iii. Hemoglobin E: Here also the β-chains are abnormal., It is present in people with hemoglobin E disease, which is also characterized by mild hemolytic, anemia and splenomegaly., iv. Hemoglobin M: It is the abnormal hemoglobin, present in the form of methemoglobin. It occurs, due to mutation of genes of both in α and β chains,, resulting in abnormal replacement of amino acids., It is present in babies affected by hemoglobin M, disease or blue baby syndrome. It is an inherited, disease, characterized by methemoglobinemia.
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Chapter 11 t Hemoglobin and Iron Metabolism, 2. Hemoglobin in Thalassemia and, Related Disorders, In thalassemia, different types of abnormal hemoglobins, are present. The polypeptide chains are decreased,, absent or abnormal. In α-thalassemia, the α-chains are, decreased, absent or abnormal and in β-thalassemia,, the β-chains are decreased, absent or abnormal, (Chapter 14). Some of the abnormal hemoglobins found, in thalassemia are hemoglobin G, H, I, Bart’s, Kenya,, Lepore and constant spring., , ABNORMAL HEMOGLOBIN DERIVATIVES, ‘Hemoglobin derivatives’ refer to a blood test to detect, and measure the percentage of abnormal hemoglobin, derivatives., Hemoglobin is the only carrier for transport of oxygen,, without which tissue death occurs within few minutes., When hemoglobin is altered, its oxygen carrying, capacity is decreased resulting in lack of oxygen. So, it, is important to know about the causes and the effects of, abnormal hemoglobin derivatives., Abnormal hemoglobin derivatives are formed by, carbon monoxide (CO) poisoning or due to some drugs, like nitrites, nitrates and sulphanamides., Abnormal hemoglobin derivatives are:, 1. Carboxyhemoglobin, 2. Methemoglobin, 3. Sulfhemoglobin., Normal percentage of hemoglobin derivatives in total, hemoglobin:, Carboxyhemoglobin : 3% to 5 %, Methemoglobin, : less than 3%, Sulfhemoglobin, : trace (undetectable)., Abnormally high levels of hemoglobin derivates, in blood produce serious effects. These derivatives, prevent the transport of oxygen resulting in oxygen lack, in tissues, which may be fatal., CARBOXYHEMOGLOBIN, Carboxyhemoglobin or carbon monoxyhemoglobin, is the abnormal hemoglobin derivative formed by the, combination of carbon monoxide with hemoglobin., Carbon monoxide is a colorless and odorless gas. Since, hemoglobin has 200 times more affinity for carbon, monoxide than oxygen, it hinders the transport of oxygen, resulting in tissue hypoxia (Chapter 127)., Normally, 1% to 3% of hemoglobin is in the form of, carboxyhemoglobin., , 79, , Sources of Carbon Monoxide, 1., 2., 3., 4., 5., 6., 7., 8., 9., , Charcoal burning, Coal mines, Deep wells, Underground drainage system, Exhaust of gasoline engines, Gases from guns and other weapons, Heating system with poor or improper ventilation, Smoke from fire, Tobacco smoking., , Signs and Symptoms of, Carbon Monoxide Poisoning, 1. While breathing air with less than 1% of CO, the Hb, saturation is 15% to 20% and mild symptoms like, headache and nausea appear, 2. While breathing air with more than 1% CO, the, Hb saturation is 30% to 40%. It causes severe, symptoms like:, i. Convulsions, ii. Cardiorespiratory arrest, iii. Unconsciousness and coma., 3. When Hb saturation increases above 50%, death, occurs., METHEMOGLOBIN, Methemoglobin is the abnormal hemoglobin derivative, formed when iron molecule of hemoglobin is oxidized, from normal ferrous state to ferric state. Methemoglobin, is also called ferrihemoglobin., Normal methemoglobin level is 0.6% to 2.5% of total, hemoglobin., Under normal circumstances also, body faces the, threat of continuous production of methemoglobin. But it, is counteracted by erythrocyte protective system called, nicotinamide adenine dinucleotide (NADH) system,, which operates through two enzymes:, 1. Diaphorase I (nicotinamide adenine dinucleotide, phosphate [NADPH]dependent reductase): Res, ponsible for 95% of the action., 2. Diaphorase II (NADPHdependent methemoglobin, reductase): Responsible for 5% of the action., These two enzymes prevent the oxidation of ferrous, iron into ferric iron., Methemoglobinemia, Methemoglobinemia is the disorder characterized by, high level of methemoglobin in blood. It leads to tissue, hypoxia, which causes cyanosis and other symptoms.
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80, , Section 2 t Blood and Body Fluids, , Causes of methemoglobinemia, Methemoglobinemia is caused by variety of factors:, 1. Common factors of daily life:, i. Well water contaminated with nitrates and, nitrites, ii. Fires, iii. Laundry ink, iv. Match sticks and explosives, v. Meat preservatives (which contain nitrates and, nitrites), vi. Mothballs (naphthalene balls), vii. Room deodorizer propellants., 2. Exposure to industrial chemicals such as:, i. Aromatic amines, ii. Fluorides, iii. Irritant gases like nitrous oxide and nitro, benzene, iv. Propylene glycol dinitrate., 3. Drugs:, i., ii., iii., iv., v., , Antibacterial drugs like sulfonamides, Antimalarial drugs like chloroquine, Antiseptics, Inhalant in cyanide antidote kit, Local anesthetics like benzocaine., , 4. Hereditary trait:, Due to deficiency of NADH-dependant reductase or, presence of abnormal hemoglobin M. Hemoglobin M is, common in babies affected by blue baby syndrome (a, pathological condition in infants, characterized by bluish, skin discoloration (cyanosis), caused by congenital heart, defect)., SULFHEMOGLOBIN, , level rises above 10 gm/dL, cyanosis occur. Usually,, serious toxic effects are not noticed., , SYNTHESIS OF HEMOGLOBIN, Synthesis of hemoglobin actually starts in proerythro, blastic stage (Fig. 11.1). However, hemoglobin appears, in the intermediate normoblastic stage only. Production of, hemoglobin is continued until the stage of reticulocyte., Heme portion of hemoglobin is synthesized in, mitochondria. And the protein part, globin is synthesized, in ribosomes., SYNTHESIS OF HEME, Heme is synthesized from succinylCoA and the glycine., The sequence of events in synthesis of hemoglobin:, 1. First step in heme synthesis takes place in the mito, chondrion. Two molecules of succinylCoA combine, with two molecules of glycine and condense to form, δ-aminolevulinic acid (ALA) by ALA synthase., 2. ALA is transported to the cytoplasm. Two molecules, of ALA combine to form porphobilinogen in the, presence of ALA dehydratase., 3. Porphobilinogen is converted into uroporphobilinogen, I by uroporphobilinogen I synthase., 4. Uroporphobilinogen I is converted into uroporpho, bilinogen III by porphobilinogen III cosynthase., 5. From uroporphobilinogen III, a ring structure, called coproporphyrinogen III is formed by, uroporphobilinogen decarboxylase., 6. Coproporphyrinogen III is transported back to the, mitochondrion, where it is oxidized to form proto, porphyrinogen IX by coproporphyrinogen oxidase, 7. Protoporphyrinogen IX is converted into proto, porphyrin IX by protoporphyrinogen oxidase., 8. Protoporphyrin IX combines with iron to form heme, in the presence of ferrochelatase., , Sulfhemoglobin is the abnormal hemoglobin derivative,, formed by the combination of hemoglobin with hydrogen, sulfide. It is caused by drugs such as phenacetin or, sulfonamides., Normal sulfhemoglobin level is less than 1% of total, hemoglobin., Sulfhemoglobin cannot be converted back into, hemoglobin. Only way to get rid of this from the body is, to wait until the affected RBCs with sulfhemoglobin are, destroyed after their lifespan., , FORMATION OF GLOBIN, , Blood Level of Sulfhemoglobin, , CONFIGURATION, , Normally, very negligible amount of sulfhemoglobin is, present in blood which is nondetectable. But when its, , Each polypeptide chain combines with one heme, molecule. Thus, after the complete configuration, each, , Polypeptide chains of globin are produced in the, ribosomes. There are four types of polypeptide chains, namely, alpha, beta, gamma and delta chains. Each, of these chains differs from others by the amino acid, sequence. Each globin molecule is formed by the, combination of 2 pairs of chains and each chain is made, of 141 to 146 amino acids. Adult hemoglobin contains, two alpha chains and two beta chains. Fetal hemoglobin, contains two alpha chains and two gamma chains.
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Chapter 11 t Hemoglobin and Iron Metabolism, , 81, , FIGURE 11.1: Synthesis of hemoglobin, , hemoglobin molecule contains 4 polypeptide chains and, 4 heme molecules., SUBSTANCES NECESSARY FOR, HEMOGLOBIN SYNTHESIS, Various materials are essential for the formation of, hemoglobin in the RBC (Refer Chapter 10 for details)., , DESTRUCTION OF HEMOGLOBIN, After the lifespan of 120 days, the RBC is destroyed, in the reticuloendothelial system, particularly in spleen, and the hemoglobin is released into plasma. Soon, the, hemoglobin is degraded in the reticuloendothelial cells, and split into globin and heme., , Globin is utilized for the resynthesis of hemoglobin., Heme is degraded into iron and porphyrin. Iron is stored, in the body as ferritin and hemosiderin, which are, reutilized for the synthesis of new hemoglobin. Porphyrin, is converted into a green pigment called biliverdin. In, human being, most of the biliverdin is converted into a, yellow pigment called bilirubin. Bilirubin and biliverdin, are together called the bile pigments (Details of bile, pigments are given in Chapter 40)., , IRON METABOLISM, IMPORTANCE OF IRON, Iron is an essential mineral and an important component, of proteins, involved in oxygen transport. So, human
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82, , Section 2 t Blood and Body Fluids, , body needs iron for oxygen transport. Iron is important, for the formation of hemoglobin and myoglobin. Iron is, also necessary for the formation of other substances, like cytochrome, cytochrome oxidase, peroxidase and, , into blood by a protein called ferroportin. In the blood,, ferric iron is converted into ferrous iron and transported., , catalase., , Immediately after absorption into blood, iron combines, with a β-globulin called apotransferrin (secreted by liver, through bile) resulting in the formation of transferrin., And iron is transported in blood in the form of transferrin., Iron combines loosely with globin and can be released, easily at any region of the body., , NORMAL VALUE AND DISTRIBUTION, OF IRON IN THE BODY, Total quantity of iron in the body is about 4 g. Approximate, distribution of iron in the body is as follows:, In the hemoglobin, : 65% to 68%, In the muscle as myoglobin, : 4%, As intracellular oxidative heme compound : 1%, In the plasma as transferrin, : 0.1%, Stored in the reticuloendothelial system, : 25% to 30%, DIETARY IRON, Dietary iron is available in two forms called heme and, nonheme., Heme Iron, Heme iron is present in fish, meat and chicken. Iron in, these sources is found in the form of heme. Heme iron, is absorbed easily from intestine., Non-heme Iron, Iron in the form of nonheme is available in vegetables,, grains and cereals. Nonheme iron is not absorbed, easily as heme iron. Cereals, flours and products of, grains which are enriched or fortified (strengthened) with, iron become good dietary sources of nonheme iron,, particularly for children and women., ABSORPTION OF IRON, Iron is absorbed mainly from the small intestine. It is, absorbed through the intestinal cells (enterocytes), by pinocytosis and transported into the blood. Bile is, essential for the absorption of iron., Iron is present mostly in ferric (Fe3+) form. It is, converted into ferrous form (Fe2+) which is absorbed into, the blood. Hydrochloric acid from gastric juice makes, the ferrous iron soluble so that it could be converted, into ferric iron by the enzyme ferric reductase from, enterocytes. From enterocytes, ferric iron is transported, , TRANSPORT OF IRON, , STORAGE OF IRON, Iron is stored in large quantities in reticuloendothelial, cells and liver hepatocytes. In other cells also it is stored, in small quantities. In the cytoplasm of the cell, iron is, stored as ferritin in large amount. Small quantity of iron, is also stored as hemosiderin., DAILY LOSS OF IRON, In males, about 1 mg of iron is excreted everyday through, feces. In females, the amount of iron loss is very much, high. This is because of the menstruation., One gram of hemoglobin contains 3.34 mg of iron., Normally, 100 mL of blood contains 15 gm of hemoglobin, and about 50 mg of iron (3.34 × 15). So, if 100 mL of, blood is lost from the body, there is a loss of about 50 mg, of iron. In females, during every menstrual cycle, about, 50 mL of blood is lost by which 25 mg of iron is lost. This, is why the iron content is always less in females than in, males., Iron is lost during hemorrhage and blood donation, also. If 450 mL of blood is donated, about 225 mg of iron, is lost., REGULATION OF TOTAL IRON IN THE BODY, Absorption and excretion of iron are maintained almost, equally under normal physiological conditions. When, the iron storage is saturated in the body, it automatically, reduces the further absorption of iron from the gastro, intestinal tract by feedback mechanism., Factors which reduce the absorption of iron:, 1. Stoppage of apotransferrin formation in the liver, so, that the iron cannot be absorbed from the intestine., 2. Reduction in the release of iron from the transferrin,, so that transferrin is completely saturated with iron, and further absorption is prevented.
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Erythrocyte, Sedimentation Rate, , Chapter, , 12, , DEFINITION, DETERMINATION, , , , WESTERGREN’S METHOD, WINTROBE’S METHOD, , NORMAL VALUES, SIGNIFICANCE OF DETERMINING ESR, VARIATIONS OF ESR, , , , PHYSIOLOGICAL VARIATION, PATHOLOGICAL VARIATION, , FACTORS AFFECTING ESR, , , , FACTORS INCREASEING ESR, FACTORS DECREASEING ESR, , DEFINITION, , Westergren Tube, , Erythrocyte sedimentation rate (ESR) is the rate at which, the erythrocytes settle down. Normally, the red blood, cells (RBCs) remain suspended uniformly in circulation., This is called suspension stability of RBCs. If blood is, mixed with an anticoagulant and allowed to stand on a, vertical tube, the red cells settle down due to gravity with, a supernatant layer of clear plasma., ESR is also called sedimentation rate, sed rate or, Biernacki reaction. It was first demonstrated by Edmund, Biernacki in 1897., , The tube is 300 mm long and opened on both ends (Fig., 12.1A). It is marked 0 to 200 mm from above down, wards. Westergren tube is used only for determining, ESR., 1.6 mL of blood is mixed with 0.4 mL of 3.8% sodium, citrate (anticoagulant) and loaded in the Westergren, tube. The ratio of blood and anticoagulant is 4:1. The, tube is fitted to the stand vertically and left undisturbed., The reading is taken at the end of 1 hour., , DETERMINATION OF ESR, There are two methods to determine ESR., 1. Westergren method, 2. Wintrobe method, WESTERGREN METHOD, In this method, Westergren tube is used to determine, ESR., , WINTROBE METHOD, In this method, Wintrobe tube is used to determine, ESR., Wintrobe Tube, Wintrobe tube is a short tube opened on only one end, (Fig. 12.1B). It is 110 mm long with 3 mm bore. Wintrobe, tube is used for determining ESR and PCV. It is marked
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84, , Section 2 t Blood and Body Fluids, , on both sides. On one side the marking is from 0 to 100, (for ESR) and on other side from 100 to 0 (for PCV)., About 1 mL of blood is mixed with anticoagulant,, ethylenediaminetetraacetic acid (EDTA). The blood is, loaded in the tube up to ‘0’ mark and the tube is placed, on the Wintrobe stand. And, the reading is taken after 1, hour., , NORMAL VALUES OF ESR, By Westergren Method, In males, : 3 to, In females : 5 to, Infants, : 0 to, By Wintrobe Method, In males, : 0 to, In females : 0 to, Infants, : 0 to, , 7, 9, 2, , mm in 1 hour, mm in 1 hour, mm in 1 hour, , 9 mm in 1 hour, 15 mm in 1 hour, 5 mm in 1 hour, , SIGNIFICANCE OF DETERMINING ESR, Erythrocyte sedimentation rate (ESR) is an easy,, inexpensive and non-specific test, which helps in diagnosis as well as prognosis. It is non-specific because it, cannot indicate the exact location or cause of disease., But, it helps to confirm the diagnosis. Prognosis means, monitoring the course of disease and response of the, patient to therapy. Determination of ESR is especially, helpful in assessing the progress of patients treated for, certain chronic inflammatory disorders such as:, 1. Pulmonary tuberculosis (Chapter 14), 2. Rheumatoid arthritis (Chapter 14), 3. Polymyalgia rheumatica (inflammatory disease, characterized by pain in shoulder and hip), 4. Temporal arteritis (inflammation of arteries of head)., , VARIATIONS OF ESR, PHYSIOLOGICAL VARIATION, 1. Age: ESR is less in children and infants because of, more number of RBCs., 2. Sex: It is more in females than in males because of, less number of RBCs., 3. Menstruation: The ESR increases during menstrua, tion because of loss of blood and RBCs, 4. Pregnancy: From 3rd month to parturition, ESR, increases up to 35 mm in 1 hour because of, hemodilution., , FIGURE 12.1: A. Westergren tube: This is used for determining, ESR; B. Wintrobe tube: This is used to determine ESR and PCV., , PATHOLOGICAL VARIATION, ESR increases in diseases such as the following, conditions:, 1. Tuberculosis, 2. All types of anemia except sickle cell anemia, 3. Malignant tumors, 4. Rheumatoid arthritis, 5. Rheumatic fever, 6. Liver diseases., ESR decreases in the following conditions:, 1. Allergic conditions, 2. Sickle cell anemia
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Chapter 12 t Erythrocyte Sedimentation Rate, 3. Peptone shock, 4. Polycythemia, 5. Severe leukocytosis., , FACTORS AFFECTING ESR, FACTORS INCREASEING ESR, 1. Specific Gravity of RBC, When the specific gravity of the RBC increases, the, cells become heavier and sedimentation is fast. So ESR, increases., , 85, , 3. Increase in Size of RBC, When the size of RBC increases (macrocyte), ESR also, increases., FACTORS DECREASING ESR, 1. Viscosity of Blood, Viscosity offers more resistance for settling of RBCs., So when the viscosity of blood increases, the ESR, decreases., 2. RBC count, , 2. Rouleaux Formation, Rouleaux formation increases the ESR. Globulin and, fibrinogen accelerate the rouleaux formation., , When RBC count increases, the viscosity of blood is, increased and ESR decreases. And when the RBC, count decreases, ESR increases.
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Chapter, , Packed Cell Volume, and Blood Indices, , , , , , , , , , , 13, , DEFINITION, METHOD OF DETERMINATION, SIGNIFICANCE OF DETERMINING, NORMAL VALUES, VARIATIONS, BLOOD INDICES, IMPORTANCE OF BLOOD INDICES, DIFFERENT BLOOD INDICES, CALCULATION OF BLOOD INDICES, , DEFINITION, , SIGNIFICANCE OF DETERMINING PCV, , Packed cell volume (PCV) is the proportion of blood, occupied by RBCs, expressed in percentage. It is the, volume of RBCs packed at the bottom of a hematocrit, tube when the blood is centrifuged. It is also called, hematocrit value or erythrocyte volume fraction (EVF)., , Determination of PCV helps in:, 1. Diagnosis and treatment of anemia, 2. Diagnosis and treatment of polycythemia, 3. Determination of extent of dehydration and recovery, from dehydration after treatment, 4. Decision of blood transfusion., , METHOD OF DETERMINATION, Blood is mixed with the anticoagulant ethylenediamine, tetraacetic acid (EDTA) or heparin and filled in hematocrit, or Wintrobe tube (110 mm long and 3 mm bore) up to 100, mark. The tube with the blood is centrifuged at a speed, of 3000 revolutions per minute (rpm) for 30 minutes., RBCs packed at the bottom form the packed cell vol, ume and the plasma remains above this. In between the, RBCs and the plasma, there is a white buffy coat, which is, formed by white blood cells and the platelets (Fig. 13.1)., In the laboratories with modern equipments, hema, tocrit is not measured directly but calculated indirectly by, autoanalyzer. It is determined by multiplying RBC count, by mean cell volume. However, some amount of plasma, is always trapped between the RBCs. So, accurate value, is obtained only by direct measurement of PCV., , NORMAL VALUES OF PCV, Normal PCV:, In males, In females, , =, =, , 40% to 45%, 38% to 42%, , VARIATIONS IN PCV, INCREASE IN PCV, PCV increases in:, 1. Polycythemia, 2. Dehydration, 3. Dengue shock syndrome: Dengue fever (tropical, disease caused by flavivirus transmitted by mosquito, Aedes aegypti) of grade III or IV severity.
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Chapter 13 t Packed Cell Volume and Blood Indices, , 87, , DIFFERENT BLOOD INDICES, Blood indices include:, 1. Mean corpuscular volume (MCV)., 2. Mean corpuscular hemoglobin (MCH)., 3. Mean corpuscular hemoglobin concentration, (MCHC)., 4. Color Index (CI)., 1. Mean Corpuscular Volume (MCV), MCV is the average volume of a single RBC and it is, expressed in cubic microns (cu µ). Normal MCV is 90 cu, µ (78 to 90 cu µ)., When MCV is normal, the RBC is called normocyte., When MCV increases, the cell is known as a macrocyte, and when it decreases, the cell is called microcyte., In pernicious anemia and megaloblastic anemia,, the RBCs are macrocytic in nature. In iron deficiency, anemia the RBCs are microcytic., 2. Mean Corpuscular Hemoglobin (MCH), MCH is the quantity or amount of hemoglobin present in, one RBC. It is expressed in micromicrogram or picogram, (pg). Normal value of MCH is 30 pg (27 to 32 pg)., 3. Mean Corpuscular Hemoglobin, Concentration (MCHC), FIGURE 13.1: Packed cell volume, , DECREASE IN PCV, PCV decreases in:, 1. Anemia, 2. Cirrhosis of liver (Chapter 40), 3. Pregnancy, 4. Hemorrhage due to ectopic pregnancy (pregnancy, due to implantation of fertilized ovum in tissues, other than uterine wall), which is characterized by, vaginal bleeding., , BLOOD INDICES, Blood indices are the calculations derived from RBC, count, hemoglobin content of blood and PCV., , IMPORTANCE OF BLOOD INDICES, Blood indices help in diagnosis of the type of anemia., , MCHC is the concentration of hemoglobin in one RBC., It is the amount of hemoglobin expressed in relation to, the volume of one RBC. So, the unit of expression is, percentage. This is the most important absolute value in, the diagnosis of anemia. Normal value of MCHC is 30%, (30% to 38%)., When MCHC is normal, the RBC is normochromic., When the MCHC decreases, the RBC is known, hypochromic. In pernicious anemia and megaloblastic, anemia, RBCs are macrocytic and normochromic or, hypochromic. In iron deficiency anemia, RBCs are, microcytic and hypochromic. A single RBC cannot be, hyperchromic because, the amount of hemoglobin, cannot increase beyond normal., 4. Color Index (CI), Color index is the ratio between the percentage of, hemoglobin and the percentage of RBCs in the blood., Actually, it is the average hemoglobin content in one cell, of a patient compared to the average hemoglobin content
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Section 2 t Blood and Body Fluids, , 88, , in one cell of a normal person. Normal color index is 1.0, (0.8 to 1.2). It was widely used in olden days. However, it, is useful in determining the type of anemia. It increases, in macrocytic (pernicious) anemia and megaloblastic, anemia. It is reduced in iron deficiency anemia. And, it is, normal in normocytic normochromic anemia., , MEAN CORPUSCULAR VOLUME, PCV in mL / 1,000 mL of blood, , MCV =, , RBC count in million/cu mm of blood, PCV in 1000 mL or in 100 mL × 10, , =, , RBC count in million/cu mm, , CALCULATION OF BLOOD INDICES, Blood indices are calculated by using different formula., These calculations require the values of RBC count,, hemoglobin content and PCV., For example, in the blood of a male subject:, RBC count, = 4 million/cu mm., Hemoglobin content = 8 g/dL, PCV, = 30%, , 30 × 10, , MCV =, , 4, , MEAN CORPUSCULAR HEMOGLOBIN, MCH =, , COLOR INDEX, , MCH =, , Hemoglobin in gram per 1000 ml of blood, RBC count in million/cu mm, Hemoglobin in gram per 100 ml of blood × 10, RBC count in million/cu mm, , Color index is calculated by dividing the hemoglobin, percentage by the RBC count percentage., =, , 80, , =, , pg., 4, Thus, MCH = 20 pg or micromicro gram., , Hemoglobin %, RBC %, , MEAN CORPUSCULAR, HEMOGLOBIN CONCENTRATION, , Hemoglobin %, =, , = 75 cu µ., , Thus, MCV = 75 cu µ, , Color index, MCV, MCH and MCHC are calculated, as follows:, , Thus, color index, , cu µ, , Hemoglobin content in the subject, Hemoglobin content in normal persons, , × 100, MCHC =, , Hemoglobin in gram/100 mL of blood, , × 100, , PCV in 100 mL of blood, =, , 8 g/dL, 15 g/dL, , × 100 = 53.3%, , 8, , =, , × 100, , 30, RBC %, =, , =, , RBC count in the subject, , × 100, , RBC count in normal persons, =, , 4 million/cu mm, 5 million/cu mm, , Hemoglobin%, RBC%, , Thus, color index = 0.67, , =, , 53.3%, 80%, , %, 30, Thus, MCHC = 26.67%., RESULTS, , × 100 = 80%, , By using these two values, CI is calculated, Color Index =, , 800, , = 0.67, , CI, = 0.67, (Normal = 0.8 to1.2), MCV, = 75 cu µ (Normal = 78 to 90 cu µ), MCH, = 20 pg, (Normal = 27 to 32 pg), MCHC = 26.67% (Normal = 30% to 38%), Results of these indices indicate that the person is, suffering from microcytic hypochromic anemia, which, commonly occurs during iron deficiency.
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Chapter, , Anemia, , 14, , INTRODUCTION, CLASSIFICATION, SIGNS AND SYMPTOMS, , INTRODUCTION, , 2. Macrocytic Normochromic Anemia, , Anemia is the blood disorder, characterized by the, reduction in:, 1. Red blood cell (RBC) count, 2. Hemoglobin content, 3. Packed cell volume (PVC)., Generally, reduction in RBC count, hemoglobin, content and PCV occurs because of:, 1. Decreased production of RBC, 2. Increased destruction of RBC, 3. Excess loss of blood from the body., All these incidents are caused either by inherited, disorders or environmental influences such as nutritional, problem, infection and exposure to drugs or toxins., , RBCs are larger in size with normal color. RBC count is, less., , CLASSIFICATION OF ANEMIA, Anemia is classified by two methods:, 1. Morphological classification, 2. Etiological classification., MORPHOLOGICAL CLASSIFICATION, Morphological classification depends upon the size and, color of RBC. Size of RBC is determined by mean corpus, cular volume (MCV). Color is determined by mean corpus, cular hemoglobin concentration (MCHC). By this method,, the anemia is classified into four types (Table 14.1):, 1. Normocytic Normochromic Anemia, Size (MCV) and color (MCHC) of RBCs are normal. But, the number of RBC is less., , 3. Macrocytic Hypochromic Anemia, RBCs are larger in size. MCHC is less, so the cells are, pale (less colored)., 4. Microcytic Hypochromic Anemia, RBCs are smaller in size with less color., ETIOLOGICAL CLASSIFICATION, On the basis of etiology (study of cause or origin),, anemia is divided into five types (Table 14.2):, 1. Hemorrhagic anemia, 2. Hemolytic anemia, 3. Nutrition deficiency anemia, 4. Aplastic anemia, 5. Anemia of chronic diseases., TABLE 14.1: Morphological classification of anemia, Type of anemia, , Size of RBC, (MCV), , Color of RBC, (MCHC), , Normocytic normochromic, , Normal, , Normal, , Normocytic hypochromic, , Normal, , Less, , Macrocytic hypochromic, , Large, , Less, , Microcytic hypochromic, , Small, , Less
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90, , Section 2 t Blood and Body Fluids, , 1. Hemorrhagic Anemia, Hemorrhage refers to excessive loss of blood (Chapter, 115). Anemia due to hemorrhage is known as hemorrhagic, anemia. It occurs both in acute and chronic hemorrhagic, conditions., , Due to continuous loss of blood, lot of iron is lost, from the body causing iron deficiency. This affects the, synthesis of hemoglobin resulting in less hemoglobin, content in the cells. The cells also become small. Hence,, the RBCs are microcytic and hypochromic (Table 14.2)., , Acute hemorrhage, , 2. Hemolytic Anemia, , Acute hemorrhage refers to sudden loss of a large quan, tity of blood as in the case of accident. Within about 24, hours after the hemorrhage, the plasma portion of blood, is replaced. However, the replacement of RBCs does, not occur quickly and it takes at least 4 to 6 weeks. So, with less number of RBCs, hemodilution occurs. How, ever, morphologically the RBCs are normocytic and, normochromic., Decreased RBC count causes hypoxia, which, stimulates the bone marrow to produce more number of, RBCs. So, the condition is corrected within 4 to 6 weeks., , Hemolysis means destruction of RBCs. Anemia due, to excessive hemolysis which is not compensated by, increased RBC production is called hemolytic anemia. It, is classified into two types:, A. Extrinsic hemolytic anemia., B. Intrinsic hemolytic anemia., A. Extrinsic hemolytic anemia: It is the type of anemia, caused by destruction of RBCs by external factors., Healthy RBCs are hemolized by factors outside the, blood cells such as antibodies, chemicals and drugs., Extrinsic hemolytic anemia is also called autoimmune, , Chronic hemorrhage, , hemolytic anemia., , It refers to loss of blood by internal or external bleeding,, over a long period of time. It occurs in conditions like, peptic ulcer, purpura, hemophilia and menorrhagia., , Common causes of external hemolytic anemia:, i. Liver failure, ii. Renal disorder, , TABLE 14.2: Etiological classification of anemia, Type of anemia, Hemorrhagic anemia, , Hemolytic anemia, , Causes, Acute loss of blood, , Normocytic, normochromic, , Chronic loss of blood, , Microcytic, hypochromic, , Extrinsic hemolytic anemia:, i. Liver failure, ii. Renal disorder, iii. Hypersplenism, iv. Burns, v. Infections – hepatitis, malaria and septicemia, vi. Drugs – Penicillin, antimalarial drugs and, sulfa drugs, vii. Poisoning by lead, coal and tar, viii. Presence of isoagglutinins like anti Rh, xi. Autoimmune diseases – rheumatoid arthritis, and ulcerative colitis, , Normocytic normochromic, , Intrinsic hemolytic anemia: Hereditary disorders, , Nutrition deficiency, anemia, , Aplastic anemia, , Anemia of chronic, diseases, , Morphology of RBC, , Sickle cell anemia: Sickle shape, Thalassemia: Small and irregular, , Iron deficiency, , Microcytic, hypochromic, , Protein deficiency, , Macrocytic, hypochromic, , Vitamin B12, , Macrocytic, normochromic/hypochromic, , Folic acid, , Megaloblastic, hypochromic, , Bone marrow disorder, , Normocytic, normochromic, , i. Noninfectious inflammatory diseases –, rheumatoid arthritis, ii. Chronic infections – tuberculosis, iii. Chronic renal failure, iv. Neoplastic disorders – Hodgkin’s disease, , Normocytic, normochromic
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Chapter 14 t Anemia, iii., iv., v., vi., , Hypersplenism, Burns, Infections like hepatitis, malaria and septicemia, Drugs such as penicillin, antimalarial drugs and, sulfa drugs, vii. Poisoning by chemical substances like lead,, coal and tar, viii. Presence of isoagglutinins like antiRh, ix. Autoimmune diseases such as rheumatoid, arthritis and ulcerative colitis., B. Intrinsic hemolytic anemia: It is the type of anemia, caused by destruction of RBCs because of the defective, RBCs. There is production of unhealthy RBCs, which are, short lived and are destroyed soon. Intrinsic hemolytic, anemia is often inherited and it includes sickle cell, anemia and thalassemia., Because of the abnormal shape in sickle cell anemia, and thalassemia, the RBCs become more fragile and, susceptible for hemolysis., Sickle cell anemia, Sickle cell anemia is an inherited blood disorder,, characterized by sickleshaped red blood cells. It is also, called hemoglobin SS disease or sickle cell disease. It, is common in people of African origin., Sickle cell anemia is due to the abnormal hemoglobin, called hemoglobin S (sickle cell hemoglobin). In this,, αchains are normal and βchains are abnormal. The, molecules of hemoglobin S polymerize into long chains, and precipitate inside the cells. Because of this, the, RBCs attain sickle (crescent) shape and become more, fragile leading to hemolysis (Fig. 14.1). Sickle cell anemia, occurs when a person inherits two abnormal genes (one, from each parent)., In children, hemolyzed sickle cells aggregate and, block the blood vessels, leading to infarction (stoppage of, blood supply). The infarction is common in small bones., The infarcted small bones in hand and foot results in, varying length in the digits. This condition is known as, hand and foot syndrome. Jaundice also occurs in these, children., Thalassemia, Thalassemia is an inherited disorder, characterized by, abnormal hemoglobin. It is also known as Cooley’s, anemia or Mediterranean anemia. It is more common, in Thailand and to some extent in Mediterranean, countries., Thalassemia is of two types:, i. αthalassemia, ii. βthalassemia., , 91, , The βthalassemia is very common among these, two., In normal hemoglobin, number of α and β polypeptide, chains is equal. In thalassemia, the production of these, chains become imbalanced because of defective, synthesis of globin genes. This causes the precipitation, of the polypeptide chains in the immature RBCs, leading, to disturbance in erythropoiesis. The precipitation also, occurs in mature red cells, resulting in hemolysis., α-Thalassemia, αthalassemia occurs in fetal life or infancy. In this, αchains are less, absent or abnormal. In adults, βchains, are in excess and in children, γchains are in excess., This leads to defective erythropoiesis and hemolysis., The infants may be stillborn or may die immediately after, birth., β-Thalassemia, In βthalassemia, βchains are less in number, absent, or abnormal with an excess of αchains. The αchains, precipitate causing defective erythropoiesis and, hemolysis., 3. Nutrition Deficiency Anemia, Anemia that occurs due to deficiency of a nutritive, substance necessary for erythropoiesis is called nutrition, deficiency anemia. The substances which are necessary, for erythropoiesis are iron, proteins and vitamins like, C, B12 and folic acid. The types of nutrition deficiency, anemia are:, Iron deficiency anemia, Iron deficiency anemia is the most common type of, anemia. It develops due to inadequate availability of, iron for hemoglobin synthesis. RBCs are microcytic and, hypochromic., Causes of iron deficiency anemia:, i. Loss of blood, ii. Decreased intake of iron, iii. Poor absorption of iron from intestine, iv. Increased demand for iron in conditions like, growth and pregnancy., Features of iron deficiency anemia: Features of iron, deficiency anemia are brittle nails, spoonshaped nails, (koilonychias), brittle hair, atrophy of papilla in tongue, and dysphagia (difficulty in swallowing)., Protein deficiency anemia, Due to deficiency of proteins, the synthesis of hemoglobin, is reduced. The RBCs are macrocytic and hypochromic.
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Chapter 14 t Anemia, , 93, , Pernicious anemia or Addison’s anemia, , 5. Anemia of Chronic Diseases, , Pernicious anemia is the anemia due to deficiency of, vitamin B12. It is also called Addison’s anemia. It is due, to atrophy of the gastric mucosa because of autoimmune, destruction of parietal cells. The gastric atrophy results, in decreased production of intrinsic factor and poor, absorption of vitamin B12, which is the maturation factor, for RBC. RBCs are larger and immature with almost, normal or slightly low hemoglobin level. Synthesis of, hemoglobin is almost normal in this type of anemia. So,, cells are macrocytic and normochromic/hypochromic., Before knowing the cause of this anemia, it was, very difficult to treat the patients and the disease was, considered to be fatal. So, it was called pernicious, anemia., Pernicious anemia is common in old age and it is, more common in females than in males. It is associated, with other autoimmune diseases like disorders of, thyroid gland, Addison’s disease, etc. Characteristic, features of this type of anemia are lemon yellow color, of skin (due to anemic paleness and mild jaundice), and red sore tongue. Neurological disorders such as, paresthesia (abnormal sensations like numbness,, tingling, burning, etc.), progressive weakness and, ataxia (muscular incoordination) are also observed in, extreme conditions., , Anemia of chronic diseases is the second common type of, anemia (next to iron deficiency anemia). It is characterized, by short lifespan of RBCs, caused by disturbance in iron, metabolism or resistance to erythropoietin action. Anemia, develops after few months of sustained disease. RBCs, are normocytic and normochromic., Common causes anemia of chronic diseases:, i. Noninfectious inflammatory diseases such, as rheumatoid arthritis (chronic inflammatory, autoimmune disorder affecting joints)., ii. Chronic infections like tuberculosis (infection, caused by Mycobacterium tuberculosis) and, abscess (collection of pus in the infected tissue), in lungs., iii. Chronic renal failure, in which the erythropoietin, secretion decreases (since erythropoietin is, necessary for the stimulation of bone marrow to, produce RBCs, its deficiency causes anemia)., iv. Neoplastic disorders (abnormal and disorganized, growth in tissue or organ) such as Hodgkin’s, disease (malignancy involving lymphocytes), and cancer of lung and breast., RBCs are generally normocytic and normochromic, in this type of anemia. However, in progressive disease, associated with iron deficiency the cells become, microcytic and hypochromic., , Megaloblastic anemia, Megaloblastic anemia is due to the deficiency of another, maturation factor called folic acid. Here, the RBCs are, not matured. The DNA synthesis is also defective, so the, nucleus remains immature. The RBCs are megaloblastic, and hypochromic., Features of pernicious anemia appear in megaloblastic, anemia also. However, neurological disorders may not, develop., 4. Aplastic Anemia, Aplastic anemia is due to the disorder of red bone, marrow. Red bone marrow is reduced and replaced, by fatty tissues. Bone marrow disorder occurs in the, following conditions:, i. Repeated exposure to Xray or gamma ray, radiation., ii. Presence of bacterial toxins, quinine, gold salts,, benzene, radium, etc., iii. Tuberculosis., iv. Viral infections like hepatitis and HIV infections., In aplastic anemia, the RBCs are normocytic and, normochromic., , SIGNS AND SYMPTOMS OF ANEMIA, SKIN AND MUCOUS MEMBRANE, Color of the skin and mucous membrane becomes pale., Paleness is more constant and prominent in buccal and, pharyngeal mucous membrane, conjunctivae, lips, ear, lobes, palm and nail bed. Skin looses the elasticity and, becomes thin and dry. Thinning, loss and early grayness, of hair occur. The nails become brittle and easily, breakable., CARDIOVASCULAR SYSTEM, There is an increase in heart rate (tachycardia) and, cardiac output. Heart is dilated and cardiac murmurs are, produced. The velocity of blood flow is increased., RESPIRATION, There is an increase in rate and force of respiration., Sometimes, it leads to breathlessness and dyspnea, (difficulty in breathing). Oxygenhemoglobin dissociation, curve is shifted to right.
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94, , Section 2 t Blood and Body Fluids, , DIGESTION, , REPRODUCTIVE SYSTEM, , Anorexia, nausea, vomiting, abdominal discomfort and, constipation are common. In pernicious anemia, there is, atrophy of papillae in tongue. In aplastic anemia, necrotic, lesions appear in mouth and pharynx., , In females, the menstrual cycle is disturbed. There, may be menorrhagia, oligomenorrhea or amenorrhea, (Chapter 80)., , METABOLISM, Basal metabolic rate increases in severe anemia., KIDNEY, Renal function is disturbed. Albuminuria is common., , NEUROMUSCULAR SYSTEM, Common neuromuscular symptoms are increased, sensitivity to cold, headache, lack of concentration, rest, lessness, irritability, drowsiness, dizziness or vertigo, (especially while standing) and fainting. Muscles become, weak and the patient feels lack of energy and fatigued, quite often and quite easily.
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Hemolysis and Fragility, of Red Blood Cells, , , , , , , Chapter, , 15, , DEFINITION, PROCESS OF HEMOLYSIS, FRAGILITY TEST, CONDITIONS WHEN HEMOLYSIS OCCURS, HEMOLYSINS, , , , CHEMICAL SUBSTANCES, SUBSTANCES OF BACTERIAL ORIGIN OR, SUBSTANCES FOUND IN BODY, , DEFINITION, , FRAGILITY TEST, , 1. Hemolysis: Hemolysis is the destruction of formed, elements. To define more specifically, it is the, process, which involves the breakdown of red blood, cells (RBCs) and liberation of hemoglobin., 2. Fragility: Susceptibility (to be affected) of RBC, to hemolysis or tendency to break easily is called, fragility (Fragile = easily broken)., Fragility is of two types:, i. Osmotic fragility, which occurs due to exposure, to hypotonic saline, ii. Mechanical fragility, which occurs due to, mechanical trauma (wound or injury)., Under normal conditions, only old RBCs are des, troyed in the reticuloendothelial system. Abnormal hemo, lysis is the process by which even younger RBCs are, destroyed in large number by the presence of hemolytic, agents or hemolysins., , Fragility test is a test that measures the resistance of, erythrocytes in hypotonic saline solution. It is done by using, sodium chloride solution at different concentrations from, 1.2% to 0.2%. The solutions at different concentrations, are taken in series of Cohn’s tubes. Then one drop of, blood to be tested is added to each tube. The sodium, chloride solution and the blood in each tube are mixed, well and left undisturbed for some time., Results can be analyzed by observing the tubes, directly or by centrifuging the tubes after 15 minutes., , PROCESS OF HEMOLYSIS, Normally, plasma and RBCs are in osmotic equilibrium., When the osmotic equilibrium is disturbed, the cells are, affected. For example, when the RBCs are immersed in, hypotonic saline the cells swell and rupture by bursting, because of endosmosis (Chapter 4). The hemoglobin is, released from the ruptured RBCs., , Direct observations, 1. If there is no hemolysis: Fluid in the tube appears, turbid, 2. If hemolysis is started: Turbidity is reduced, 3. If hemolysis is completed: Fluid becomes clear., Observations after centrifugation, 1. If there is no hemolysis: Cells sediment at the bottom, with clear colorless fluid above, 2. If hemolysis is started: Cell sedimentation is less, and the fluid becomes slightly reddish because of, the release of small amount of hemoglobin from few, hemolyzed RBCs, 3. If hemolysis is completed: Fluid becomes more, reddish without any sedimentation due to release of
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96, , Section 2 t Blood and Body Fluids, , more amount of hemoglobin from all the hemolyzed, cells., Index for Fragility, After 20 minutes:, No hemolysis, = up to 0.6%, Onset of hemolysis, = around 0.45%, Completion of hemolysis = around 0.35%, At 0.45%, only the older cells are destroyed, because, their membrane is fragile. So, these cells, cannot withstand this hypotonicity. But, younger cells, are not affected. At 0.35%, even the younger cells are, destroyed., , CONDITIONS WHEN HEMOLYSIS OCCURS, 1., 2., 3., 4., , Hemolytic jaundice, Antigenantibody reactions, Poisoning by chemicals or toxins, While using artificial kidney for hemodialysis or, heartlung machine during cardiac surgery (rare, occasions)., , HEMOLYSINS, Hemolysins or hemolytic agents are the substances,, which cause destruction of RBCs. The hemolysins are, of two types:, A. Chemical substances, , B. Substances of bacterial origin or substances found, in body., A. CHEMICAL SUBSTANCES, 1., 2., 3., 4., 5., 6., 7., 8., 9., , Alcohol, Benzene, Chloroform, Ether, Acids, Alkalis, Bile salts, Saponin, Chemical poisons like:, i. Arsenial preparations, ii. Carbolic acid, iii. Nitrobenzene, iv. Resin., , B. SUBSTANCES OF BACTERIAL ORIGIN OR, SUBSTANCES FOUND IN BODY, 1. Toxic substances or toxins from bacteria:, i. Streptococcus, ii. Staphylococcus, iii. Tetanus bacillus, etc., 2. Venom of poisonous snakes like cobra, 3. Hemolysins from normal tissues.
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Chapter, , White Blood Cells, , , , , , , , , , , 16, , INTRODUCTION, CLASSIFICATION, MORPHOLOGY, NORMAL COUNT, VARIATIONS, LIFESPAN, PROPERTIES, FUNCTIONS, LEUKOPOIESIS, , INTRODUCTION, , 1. Granulocytes, , White blood cells (WBCs) or leukocytes are the colorless, and nucleated formed elements of blood (leuko is derived, from Greek word leukos = white). Alternate spelling for, leukocytes is leucocytes., Compared to RBCs, the WBCs are larger in size, and lesser in number. Yet functionally, these cells are, important like RBCs because of their role in defense, mechanism of body and protect the body from invading, organisms by acting like soldiers., , Depending upon the staining property of granules, the, granulocytes are classified into three types:, i. Neutrophils with granules taking both acidic and, basic stains., ii. Eosinophils with granules taking acidic stain., iii. Basophils with granules taking basic stain., , WBCs Vs RBCs, WBCs differ from RBCs in many aspects. The differences, between WBCs and RBCs are given in Table 16.1., 1. Larger in size., 2. Irregular in shape., 3. Nucleated., 4. Many types., 5. Granules are present in some type of WBCs., 6. Lifespan is shorter., , CLASSIFICATION, Some of the WBCs have granules in the cytoplasm., Based on the presence or absence of granules in the, cytoplasm, the leukocytes are classified into two groups:, 1. Granulocytes which have granules., 2. Agranulocytes which do not have granules., , 2. Agranulocytes, Agranulocytes have plain cytoplasm without granules., Agranulocytes are of two types:, i. Monocytes., ii. Lymphocytes., , MORPHOLOGY OF WHITE BLOOD CELLS, NEUTROPHILS, Neutrophils which are also known as polymorphs have, fine or small granules in the cytoplasm. The granules take, acidic and basic stains. When stained with Leishman’s, stain (which contains acidic eosin and basic methylene, blue) the granules appear violet in color., Nucleus is multilobed (Fig. 16.1). The number of, lobes in the nucleus depends upon the age of cell. In, younger cells, the nucleus is not lobed. And in older, neutrophils, the nucleus has 2 to 5 lobes. The diameter
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98, , Section 2 t Blood and Body Fluids, , TABLE 16.1: Differences between WBCs and RBCs, Feature, , WBCs, , RBCs, , of cell is 10 to 12 µ (Table 16.2). The neutrophils are, ameboid in nature., EOSINOPHILS, , Color, , Colorless, , Red, , Number, , Less: 4,000 to, 11,000/cu mm, , More: 4.5 to 5.5, million/cu mm, , Size, , Larger, Maximum diameter =, 18 µ, , Smaller, Maximum diameter =, 7.4 µ, , Shape, , Irregular, , Disk-shaped and, biconcave, , BASOPHILS, , Nucleus, , Present, , Absent, , Granules, , Present in some types, , Absent, , Types, , Many types, , Only one type, , Basophils also have coarse granules in the cytoplasm., The granules stain purple blue with methylene blue., Nucleus is bilobed. Diameter of the cell is 8 to 10 µ., , Lifespan, , Shorter, ½ to 15 days, , Longer, 120 days, , Eosinophils have coarse (larger) granules in the, cytoplasm, which stain pink or red with eosin. Nucleus, is bilobed and spectacle-shaped. Diameter of the cell, varies between 10 and 14 µ., , MONOCYTES, Monocytes are the largest leukocytes with diameter of, 14 to 18 µ. The cytoplasm is clear without granules., Nucleus is round, oval and horseshoe shaped, bean, shaped or kidney shaped. Nucleus is placed either in, the center of the cell or pushed to one side and a large, amount of cytoplasm is seen., LYMPHOCYTES, Like monocytes, the lymphocytes also do not have, granules in the cytoplasm. Nucleus is oval, bean-shaped, or kidney-shaped. Nucleus occupies the whole of the, cytoplasm. A rim of cytoplasm may or may not be seen., Types of Lymphocytes, Depending upon the size, lymphocytes are divided into, two groups:, 1. Large lymphocytes: Younger cells with a diameter of, 10 to 12 µ., 2. Small lymphocytes: Older cells with a diameter of 7, to 10 µ., Depending upon the function, lymphocytes are, divided into two types:, 1. T lymphocytes: Cells concerned with cellular immunity., 2. B lymphocytes: Cells concerned with humoral, immunity., TABLE 16.2: Diameter and lifespan of WBCs, , FIGURE 16.1: Different white blood cells, , WBC, , Diameter, (µ), , Lifespan, (days), , Neutrophils, , 10 to 12, , 2 to 5, , Eosinophils, , 10 to 14, , 7 to 12, , Basophils, , 8 to 10, , 12 to 15, , Monocytes, , 14 to 18, , 2 to 5, , 7 to 12, , ½ to 1, , Lymphocytes
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Chapter 16 t White Blood Cells, , NORMAL WHITE BLOOD CELL COUNT, 1. Total WBC count (TC): 4,000 to 11,000/cu mm of, blood., 2. Differential WBC count (DC): Given in Table 16.3., , VARIATIONS IN WHITE BLOOD, CELL COUNT, , Leukocytosis is the increase in total WBC count., Leukocytosis occurs in both physiological and pathological conditions., , All types of leukocytes do not share equally in the, increase or decrease of total leukocyte count. In general,, the neutrophils and lymphocytes vary in opposite, directions., Leukocytosis, , Leukopenia, Leukopenia is the decrease in total WBC count. The term, leukopenia is generally used for pathological conditions, only., Granulocytosis, Granulocytosis is the abnormal increase in the number, of granulocytes., , Leukocytosis is the increase in total leukocyte (WBC), count. It occurs in conditions such as:, 1. Infections, 2. Allergy, 3. Common cold, 4. Tuberculosis, 5. Glandular fever., Leukemia, , Granulocytopenia, Granulocytopenia is the abnormal reduction in the, number of granulocytes., Agranulocytosis, Agranulocytosis is the acute pathological condition, characterized by absolute lack of granulocytes., PHYSIOLOGICAL VARIATIONS, 1. Age: WBC count is about 20,000 per cu mm in, infants and about 10,000 to 15,000 per cu mm of, blood in children. In adults, it ranges between 4,000, and 11,000 per cu mm of blood., 2. Sex: Slightly more in males than in females., 3. Diurnal variation: Minimum in early morning and, maximum in the afternoon., TABLE 16.3: Normal values of different WBCs, Percentage, , Absolute value, per cu mm, , Neutrophils, , 50 to 70, , 3,000 to 6,000, , Eosinophils, , 2 to 4, , 150 to 450, , Basophils, , 0 to 1, , 0 to 100, , Monocytes, , 2 to 6, , 200 to 600, , 20 to 30, , 1,500 to 2,700, , Lymphocytes, , Exercise: Increases slightly., Sleep: Decreases., Emotional conditions like anxiety: Increases., Pregnancy: Increases., Menstruation: Increases., Parturition: Increases., , PATHOLOGICAL VARIATIONS, , Leukocytosis, , WBC, , 4., 5., 6., 7., 8., 9., , 99, , Leukemia is the condition which is characterized by, abnormal and uncontrolled increase in leukocyte count, more than 1,000,000/cu mm. It is also called blood, cancer., Leukopenia, Leukopenia is the decrease in the total WBC count. It, occurs in the following pathological conditions:, 1. Anaphylactic shock, 2. Cirrhosis of liver, 3. Disorders of spleen, 4. Pernicious anemia, 5. Typhoid and paratyphoid, 6. Viral infections., Variation in Differential Leukocyte Count, Differential leukocyte count varies in specific diseases., Details are given in Table 16.4., Neutrophilia, Neutrophilia or neutrophilic leukocytosis is the increase, in neutrophil count. It occurs in the following conditions:, 1. Acute infections, 2. Metabolic disorders, 3. Injection of foreign proteins
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100 Section 2 t Blood and Body Fluids, 4. Injection of vaccines, 5. Poisoning by chemicals and drugs like lead, mercury,, camphor, benzene derivatives, etc., 6. Poisoning by insect venom, 7. After acute hemorrhage., , Eosinophilia, Eosinophilia is the increase in eosinophil count and it, occurs in:, 1. Asthma and other allergic conditions, 2. Blood parasitism (malaria, filariasis), , TABLE 16.4: Pathological variations in different types of WBCs, Disorder, , Variation, , Conditions, , Increase in neutrophil count, , 1. Acute infections, 2. Metabolic disorders, 3. Injection of foreign proteins, 4. Injection of vaccines, 5. Poisoning by chemicals and drugs like lead, mercury,, camphor, benzene derivatives, etc., 6. Poisoning by insect venom, 7. After acute hemorrhage, , Decrease in neutrophil count, , 1. Bone marrow disorders, 2. Tuberculosis, 3. Typhoid, 4. Autoimmune diseases, , Increase in eosinophil count, , 1. Allergic conditions like asthma, 2. Blood parasitism (malaria, filariasis), 3. Intestinal parasitism, 4. Scarlet fever, , Eosinopenia, , Decrease in eosinophil count, , 1. Cushing’s syndrome, 2. Bacterial infections, 3. Stress, 4. Prolonged administration of drugs like steroids, ACTH and, epinephrine, , Basophilia, , Increase in basophil count, , 1. Smallpox, 2. Chickenpox, 3. Polycythemia vera, , Basopenia, , Decrease in basophil count, , 1. Urticaria (skin disorder), 2. Stress, 3. Prolonged exposure to chemotherapy or radiation therapy, , Monocytosis, , Increase in monocyte count, , 1. Tuberculosis, 2. Syphilis, 3. Malaria, 4. Kala-azar, , Monocytopenia, , Decrease in monocyte count, , Prolonged use of prednisone (immunosuppressant steroid), , Increase in lymphocyte count, , 1. Diphtheria, 2. Infectious hepatitis, 3. Mumps, 4. Malnutrition, 5. Rickets, 6. Syphilis, 7. Thyrotoxicosis, 8. Tuberculosis, , Decrease in lymphocyte count, , 1. AIDS, 2. Hodgkin’s disease (cancer of lymphatic system), 3. Malnutrition, 4. Radiation therapy, 5. Steroid administration, , Neutrophilia or, neutrophilic, leukocytosis, , Neutropenia, , Eosinophilia, , Lymphocytosis, , Lymphocytopenia
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Chapter 16 t White Blood Cells 101, 3. Intestinal parasitism, 4. Scarlet fever., Basophilia, Basophilia is the increase in basophil count and it occurs, in:, 1. Smallpox, 2. Chickenpox, 3. Polycythemia vera., Monocytosis, Monocytosis is the increase in monocyte count and it, occurs in:, 1. Tuberculosis, 2. Syphilis, 3. Malaria, 4. Kala-azar, 5. Glandular fever., Lymphocytosis, Lymphocytosis is the increase in lymphocyte count and, it occurs in:, 1. Diphtheria, 2. Infectious hepatitis, 3. Mumps, 4. Malnutrition, 5. Rickets, 6. Syphilis, 7. Thyrotoxicosis, 8. Tuberculosis., Neutropenia, Neutropenia is the decrease in neutrophil count. It, occurs in:, 1. Bone marrow disorders, 2. Tuberculosis, 3. Typhoid, 4. Vitamin deficiencies, 5. Autoimmune diseases., Eosinopenia, Decrease in eosinophil count is called eosinopenia. It, occurs in:, 1. Cushing’s syndrome, 2. Bacterial infections, 3. Stress, 4. Prolonged administration of drugs such as steroids,, ACTH, epinephrine., , Basopenia, Basopenia or basophilic leukopenia is the decrease in, basophil count. It occurs in:, 1. Urticaria (skin disorder), 2. Stress, 3. Prolonged exposure to chemotherapy or radiation, therapy., Monocytopenia, Monocytopenia is the decrease in monocyte count. It, occurs in:, 1. Prolonged use of prednisone (immunosuppressant, steroid), 2. AIDS, 3. Chronic lymphoid leukemia., Lymphocytopenia, Lymphocytopenia is the decrease in lymphocytes. It, occurs in:, 1. AIDS, 2. Hodgkin’s disease (cancer of the lymphatic system), 3. Malnutrition, 4. Radiation therapy, 5. Steroid administration., , LIFESPAN OF WHITE BLOOD CELLS, Lifespan of WBCs is not constant. It depends upon the, demand in the body and their function. Lifespan of these, cells may be as short as half a day or it may be as long, as 3 to 6 months. Lifespan of WBCs is given in Table, 16.2., , PROPERTIES OF WHITE BLOOD CELLS, 1. Diapedesis, Diapedesis is the process by which the leukocytes, squeeze through the narrow blood vessels., 2. Ameboid Movement, Neutrophils, monocytes and lymphocytes show amebic, movement, characterized by protrusion of the cytoplasm, and change in the shape., 3. Chemotaxis, Chemotaxis is the attraction of WBCs towards the injured, tissues by the chemical substances released at the site, of injury.
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102 Section 2 t Blood and Body Fluids, 4. Phagocytosis, Neutrophils and monocytes engulf the foreign bodies by, means of phagocytosis (Chapter 3)., , FUNCTIONS OF WHITE BLOOD CELLS, Generally, WBCs play an important role in defense, mechanism. These cells protect the body from invading, organisms or foreign bodies, either by destroying or, inactivating them. However, in defense mechanism,, each type of WBCs acts in a different way., NEUTROPHILS, Neutrophils play an important role in the defense, mechanism of the body. Along with monocytes, the, neutrophils provide the first line of defense against the, invading microorganisms. The neutrophils are the free, cells in the body and wander freely through the tissue, and practically, no part of the body is spared by these, leukocytes., Substances Present in Granules and Cytoplasm, of Neutrophils, Granules of neutrophils contain enzymes like proteases,, myeloperoxidases, elastases and metalloproteinases, (Table 16.5). These enzymes destroy the microorganisms., The granules also contain antibody like peptides called, cathelicidins and defensins, which are antimicrobial, peptides and are active against bacteria and fungi., Membrane of neutrophils contains an enzyme, called NADPH oxidase (dihydronicotinamide adenine, dinucleotide phosphate oxidase). It is activated by the, toxic metabolites released from infected tissues. The, activated NADPH oxidase is responsible for bactericidal, action of neutrophils (see below)., All these substances present in the granules and cell, membrane make the neutrophil a powerful and effective, killer machine., Neutrophils also secrete platelet-activating factor, (PAF), which is a cytokine. It accelerates the aggregation, of platelets during injury to the blood vessel, resulting in, prevention of excess loss of blood., Mechanism of Action of Neutrophils, Neutrophils are released in large number at the site, of infection from the blood. At the same time, new, neutrophils are produced from the progenitor cells. All, the neutrophils move by diapedesis towards the site of, infection due to chemotaxis., Chemotaxis occurs due to the attraction by some, chemical substances called chemoattractants, which are, , released from the infected area. After reaching the area,, the neutrophils surround the area and get adhered to the, infected tissues. Chemoattractants increase the adhesive, nature of neutrophils so that all the neutrophils become, sticky and get attached firmly to the infected area. Each, neutrophil can hold about 15 to 20 microorganisms at a, time. Now, the neutrophils start destroying the invaders., First, these cells engulf the bacteria and then destroy, them by means of phagocytosis (Chapter 3)., Respiratory Burst, Respiratory burst is a rapid increase in oxygen, consumption during the process of phagocytosis by, neutrophils and other phagocytic cells. Nicotinamide, adenine dinucleotide phosphate (NADPH) oxidase is, responsible for this phenomenon. During respiratory, burst, the free radical O2– is formed. 2O2– combine, with 2H+ to form H2O2 (hydrogen peroxide). Both O2–, and H2O2 are the oxidants having potent bactericidal, action., Pus and Pus Cells, Pus is the whitish yellow fluid formed in the infected, tissue by the dead WBCs, bacteria or foreign bodies and, cellular debris. It consists of white blood cells, bacteria, or other foreign bodies and cellular debris. The dead, WBCs are called pus cells., During the battle against the bacteria, many WBCs, are killed by the toxins released from the bacteria. The, dead cells are collected in the center of infected area., The dead cells together with plasma leaked from the, blood vessel, liquefied tissue cells and RBCs escaped, from damaged blood vessel (capillaries) constitute the, pus., EOSINOPHILS, Eosinophils play an important role in the defense, mechanism of the body against the parasites. During, parasitic infections, there is a production of a large, number of eosinophils which move towards the tissues, affected by parasites. Eosinophil count increases also, during allergic diseases like asthma., Eosinophils are responsible for detoxification,, disintegration and removal of foreign proteins., Mechanism of Action of Eosinophils, Eosinophils are neither markedly motile nor phagocytic, like the neutrophils. Some of the parasites are larger in, size. Still eosinophils attack them by some special type, of cytotoxic substances present in their granules. When
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Chapter 16 t White Blood Cells 103, TABLE 16.5: Substances secreted by WBCs, WBC, , Substance secreted, , Action, , Proteases, Myeloperoxidases, Elastases, , Destruction of microorganisms, , Metalloproteinases, Neutrophil, , Eosinophil, , Defensins, , Antimicrobial action, Anti-inflammatory action, Wound healing, Chemotaxis, , Cathelicidins, , Antimicrobial action, , NADPH oxidase, , Bactericidal action, , Platelet-activating factor, , Aggregation of platelets, , Eosinophil peroxidase, , Destruction of worms, bacteria and tumor cells, , Major basic protein, , Destruction of worms, , Eosinophil cationic protein, , Destruction of worms, Neurotoxic action, , Eosinophil-derived neurotoxin, , Neurotoxic action, , Interleukin-4 and 5, , Acceleration of inflammatory response, Destruction of invading organisms, , Heparin, , Prevention of intravascular blood clotting, , Histamine, Bradykinin, Basophil, , Serotonin, Proteases, Myeloperoxidases, , Monocyte, , T lymphocytes, , Production of acute hypersensitivity reactions, , Destruction of microorganisms, , Interleukin-4, , Acceleration of inflammatory response, Destruction of invading organisms, , Interleukin-1, , Acceleration of inflammatory response, Destruction of invading organisms, , Colony stimulation factor, , Formation of colony forming blastocytes, , Platelet-activating factor, , Aggregation of platelets, , Chemokines, , Chemotaxis, , Interleukin-2, 4 and 5, , Acceleration of inflammatory response, Destruction of invading organisms, Activation of T cells, , Gamma interferon, , Stimulation of phagocytic actions of cytotoxic cells, macrophages, and natural killer cells, , Lysosomal enzymes, , Destruction of invading organisms, , Tumor necrosis factor, , Necrosis of tumor, Activation of immune system, Promotion of inflammation, , Chemokines, , Chemotaxis, Contd...
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104 Section 2 t Blood and Body Fluids, , B lymphocytes, , Immunoglobulins, , Destruction of invading organisms, , Tumor necrosis factor, , Necrosis of tumor, Activation of immune system, Acceleration of inflammatory response, , Chemokines, , Chemotaxis, , released over the invading parasites from the granules,, these substances become lethal and destroy the, parasites. The lethal substances present in the granules, of eosinophils and released at the time of exposure to, parasites or foreign proteins are:, 1. Eosinophil peroxidase: This enzyme is capable of, destroying helminths (parasitic worms), bacteria, and tumor cells., 2. Major basic protein (MBP): It is very active against, helminths. It destroys the parasitic worms by, causing distension (ballooning) and detachment of, the tegumental sheath (skin-like covering) of these, organisms., 3. Eosinophil cationic protein (ECP): This substance is, the major destroyer of helminths and it is about 10, times more toxic than MBP. It destroys the parasites, by means of complete disintegration. It is also a, neurotoxin., 4. Eosinophil-derived neurotoxin: It destroys the nerve, fibers particularly, the myelinated nerve fibers., 5. Cytokines: Cytokines such as interleukin-4 and, interleukin-5 accelerate inflammatory responses by, activating eosinophils. These cytokines also kill the, invading organisms., BASOPHILS, Basophils play an important role in healing processes., So their number increases during healing process., Basophils also play an important role in allergy, or acute hypersensitivity reactions (allergy). This is, because of the presence of receptors for IgE in basophil, membrane., Mechanism of Action of Basophils, Functions of basophils are executed by the release of, some important substances from their granules such, as:, 1. Heparin: Heparin is essential to prevent the, intravascular blood clotting., 2. Histamine, slow-reacting substances of anaphylaxis,, bradykinin and serotonin: Theses substances, produce the acute hypersensitivity reactions by, causing vascular and tissue responses., 3. Proteases and myeloperoxidase: These enzymes, destroy the microorganisms., , 4. Cytokine: Cytokine such as interleukin-4 accelerates, inflammatory responses and kill the invading, organisms., Mast Cell, Mast cell is a large tissue cell resembling the basophil., Generally, mast cells are found along with the blood, vessels and are prominently seen in the areas such as, skin, mucosa of the lungs and digestive tract, mouth,, conjunctiva and nose. These cells usually do not enter, the bloodstream., Origin, Mast cells are developed in the bone marrow, but their, precursor cells are different. After differentiation, the, immature mast cells enter the tissues. Maturation of, mast cells takes place only after entering the tissue., Functions, Mast cell plays an important role in producing the, hypersensitivity reactions like allergy and anaphylaxis, (Chapter 17). When activated, the mast cell immediately, releases various chemical mediators from its granules, into the interstitium. Two types of substances are, secreted by mast cell:, 1. Preformed mediators: These substances are already, formed and stored in secretory granules. These, substances are histamine, heparin, serotonin,, hydrolytic enzymes, proteoglycans and chondroitin, sulfates., 2. Newly generated mediators: These substances are, absent in the mast cell during resting conditions, and are produced only during activation. These, substances are arachidonic acid derivatives such as, leukotriene C (LTC), prostaglandin and cytokines., MONOCYTES, Monocytes are the largest cells among the leukocytes., Like neutrophils, monocytes also are motile and, phagocytic in nature. These cells wander freely through, all tissues of the body.
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Chapter 16 t White Blood Cells 105, Monocytes play an important role in defense of the, body. Along with neutrophils, these leukocytes provide, the first line of defense., Monocytes secrete:, 1. Interleukin-1 (IL-1)., 2. Colony stimulating factor (M-CSF)., 3. Platelet-activating factor (PAF)., Monocytes are the precursors of the tissue macrophages. Matured monocytes stay in the blood only for, few hours. Afterwards, these cells enter the tissues from, the blood and become tissue macrophages. Examples, of tissue macrophages are Kupffer cells in liver, alveolar, macrophages in lungs and macrophages in spleen., Functions of macrophages are discussed in Chapter 24., , LYMPHOCYTES, Lymphocytes play an important role in immunity., Functionally, the lymphocytes are classified into two, categories, namely T lymphocytes and B lymphocytes., T lymphocytes are responsible for the development of, cellular immunity and B lymphocytes are responsible for, the development of humoral immunity. The functions of, these two types of lymphocytes are explained in detail, in Chapter 17., , LEUKOPOIESIS, Leukopoiesis is the development and maturation of, leukocytes (Fig. 16.2)., , FIGURE 16.2: Leukopoiesis
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106 Section 2 t Blood and Body Fluids, STEM CELLS, , Colony stimulating Factors, , Committed pluripotent stem cell gives rise to leukocytes, through various stages. Details are given in Chapter, 10., , Colony stimulating factors (CSF) are proteins which, cause the formation of colony forming blastocytes., Colony stimulating factors are of three types:, 1. Granulocyte-CSF (G-CSF) secreted by monocytes, and endothelial cells, 2. Granulocyte-monocyte-CSF (GM-CSF) secreted by, monocytes, endothelial cells and T lymphocytes, 3. Monocyte-CSF (M-CSF) secreted by monocytes, and endothelial cells., , FACTORS NECESSARY FOR LEUKOPOIESIS, Leukopoiesis is influenced by hemopoietic growth, factors and colony stimulating factors. Hemopoietic, growth factors are discussed in Chapter 10.
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Immunity, , , , , , , , , , , , , Chapter, , 17, , DEFINITION AND TYPES OF IMMUNITY, DEVELOPMENT AND PROCESSING OF LYMPHOCYTES, ANTIGENS, DEVELOPMENT OF CELL-MEDIATED IMMUNITY, DEVELOPMENT OF HUMORAL IMMUNITY, NATURAL KILLER CELL, CYTOKINES, IMMUNIZATION, IMMUNE DEFICIENCY DISEASES, AUTOIMMUNE DISEASES, ALLERGY AND IMMUNOLOGICAL HYPERSENSITIVITY REACTIONS, , DEFINITION AND TYPES OF IMMUNITY, , ACQUIRED IMMUNITY OR SPECIFIC IMMUNITY, , Immunity is defined as the capacity of the body to resist, pathogenic agents. It is the ability of body to resist the, entry of different types of foreign bodies like bacteria,, virus, toxic substances, etc., Immunity is of two types:, I. Innate immunity., II. Acquired immunity., , Acquired immunity is the resistance developed in the, body against any specific foreign body like bacteria,, viruses, toxins, vaccines or transplanted tissues. So, this, type of immunity is also known as specific immunity., It is the most powerful immune mechanism that, protects the body from the invading organisms or toxic, substances. Lymphocytes are responsible for acquired, immunity (Fig. 17.1)., , INNATE IMMUNITY OR NON-SPECIFIC IMMUNITY, Innate immunity is the inborn capacity of the body to, resist pathogens. By chance, if the organisms enter, the body, innate immunity eliminates them before the, development of any disease. It is otherwise called the, natural or non-specific immunity., This type of immunity represents the first line of, defense against any type of pathogens. Therefore, it is, also called non-specific immunity., Mechanisms of Innate Immunity, Various mechanisms of innate immunity are given in, Table 17.1., , Types of Acquired Immunity, Two types of acquired immunity develop in the body:, 1. Cellular immunity, 2. Humoral immunity., Lymphocytes are responsible for the development, of these two types of immunity., , DEVELOPMENT AND PROCESSING, OF LYMPHOCYTES, In fetus, lymphocytes develop from the bone marrow, (Chapter 10). All lymphocytes are released in the, circulation and are differentiated into two categories.
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108 Section 2 t Blood and Body Fluids, TABLE 17.1: Mechanisms of innate immunity, Structures and Mediators, , Mechanism, , Gastrointestinal tract, , Enzymes in digestive juices and the acid in stomach destroy the toxic substances or, organisms entering digestive tract through food, Lysozyme present in saliva destroys bacteria, , Respiratory system, , Defensins and cathelicidins in epithelial cells of air passage are antimicrobial peptides, Neutrophils, lymphocytes, macrophages and natural killer cells present in lungs act, against bacteria and virus, , Urinogenital system, , Acidity in urine and vaginal fluid destroy the bacteria, , Skin, , The keratinized stratum corneum of epidermis protects the skin against toxic chemicals, The β-defensins in skin are antimicrobial peptides, Lysozyme secreted in skin destroys bacteria, , Phagocytic cells, , Neutrophils, monocytes and macrophages ingest and destroy the microorganisms and, foreign bodies by phagocytosis, , Interferons, , Inhibit multiplication of viruses, parasites and cancer cells, , Complement proteins, , Accelerate the destruction of microorganisms, , The two categories are:, 1. T lymphocytes or T cells, which are responsible for, the development of cellular immunity, 2. B lymphocytes or B cells, which are responsible for, humoral immunity., T LYMPHOCYTES, T lymphocytes are processed in thymus. The processing, occurs mostly during the period between just before birth, and few months after birth., Thymus secretes a hormone called thymosin, which, plays an important role in immunity. It accelerates the, proliferation and activation of lymphocytes in thymus. It, also increases the activity of lymphocytes in lymphoid, tissues., Types of T Lymphocytes, During the processing, T lymphocytes are transformed, into four types:, 1. Helper T cells or inducer T cells. These cells are, also called CD4 cells because of the presence of, molecules called CD4 on their surface., 2. Cytotoxic T cells or killer T cells. These cells are, also called CD8 cells because of the presence of, molecules called CD8 on their surface., 3. Suppressor T cells., 4. Memory T cells., Storage of T Lymphocytes, After the transformation, all the types of T lymphocytes, leave the thymus and are stored in lymphoid tissues of, lymph nodes, spleen, bone marrow and GI tract., , B LYMPHOCYTES, B lymphocytes were first discovered in the bursa of, Fabricius in birds, hence the name B lymphocytes., Bursa of Fabricius is a lymphoid organ situated near, the cloaca of birds. Bursa is absent in mammals and the, processing of B lymphocytes takes place in liver (during, fetal life) and bone marrow (after birth)., Types of B Lymphocytes, After processing, the B lymphocytes are transformed, into two types:, 1. Plasma cells., 2. Memory cells., Storage of B Lymphocytes, After transformation, the B lymphocytes are stored in the, lymphoid tissues of lymph nodes, spleen, bone marrow, and the GI tract., , ANTIGENS, DEFINITION AND TYPES, Antigens are the substances which induce specific, immune reactions in the body., Antigens are of two types:, 1. Autoantigens or self antigens present on the body’s, own cells such as ‘A’ antigen and ‘B’ antigen in, RBCs., 2. Foreign antigen s or non-self antigens that enter the, body from outside.
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Chapter 17 t Immunity 109, , FIGURE 17.1: Schematic diagram showing development of immunity, , NON-SELF ANTIGENS, Following are non-self antigens:, 1. Receptors on the cell membrane of microbial, organisms such as bacteria, viruses and fungi., , 2. Toxins from microbial organisms., 3. Materials from transplanted organs or incompatible, blood cells., 4. Allergens or allergic substances like pollen grains.
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110 Section 2 t Blood and Body Fluids, Types of Non-self Antigens, , 1. Macrophages, , Non-self antigens are classified into two types, depending, upon the response developed against them in the body:, 1. Antigens, which induce the development of immunity, or production of antibodies (immunogenicity)., 2. Antigens, which react with specific antibodies and, produce allergic reactions (allergic reactivity). (The, allergic reaction is explained in the later part of this, chapter)., , Macrophages are the large phagocytic cells, which, digest the invading organisms to release the antigen., The macrophages are present along with lymphocytes, in almost all the lymphoid tissues., 2. Dendritic Cells, , DEVELOPMENT OF, CELL-MEDIATED IMMUNITY, , Dendritic cells are nonphagocytic in nature. Based on, the location, dendritic cells are classified into three, categories:, i. Dendritic cells of spleen, which trap the antigen, in blood., ii. Follicular dendritic cells in lymph nodes, which, trap the antigen in the lymph., iii. Langerhans dendritic cells in skin, which trap the, organisms coming in contact with body surface., , INTRODUCTION, , 3. B Lymphocytes, , Cell-mediated immunity is defined as the immunity, developed by cell-mediated response. It is also called, cellular immunity or T cell immunity. It involves several, types of cells such as T lymphocytes, macrophages and, natural killer cells and hence the name cell mediated, immunity. Cell-mediated immunity does not involve, antibodies., Cellular immunity is the major defense mechanism, against infections by viruses, fungi and few bacteria like, tubercle bacillus. It is also responsible for delayed allergic, reactions and the rejection of transplanted tissues., Cell-mediated immunity is offered by T lymphocytes, and it starts developing when T cells come in contact, with the antigens. Usually, the invading microbial or, non-microbial organisms carry the antigenic materials., These antigenic materials are released from invading, organisms and are presented to the helper T cells by, antigen-presenting cells., , Recently, it is found that B lymphocytes also act as, antigen-presenting cells. Thus, the B cells function as, both antigen-presenting cells and antigen receiving, cells. However, B cells are the least efficient antigenpresenting cells and need to be activated by helper T, cells., , CHEMICAL NATURE OF THE ANTIGENS, Antigens are mostly the conjugated proteins like, lipoproteins, glycoproteins and nucleoproteins., , ANTIGEN-PRESENTING CELLS, Antigen-presenting cells are the special type of cells, in the body, which induce the release of antigenic, materials from invading organisms and later present, these materials to the helper T cells., Types of Antigen-Presenting Cells, Antigen-presenting cells are of three types:, 1. Macrophages, 2. Dendritic cells, 3. B lymphocytes., Among these cells, macrophages are the major antigen-presenting cells., , Role of Antigen-presenting Cells, Invading foreign organisms are either engulfed by, macrophages through phagocytosis or trapped by, dendritic cells. Later, the antigen from these organisms, is digested into small peptide products. These antigenic, peptide products move towards the surface of the, antigen-presenting cells and bind with human leukocyte, antigen (HLA). HLA is a genetic matter present in the, molecule of class II major histocompatiblility complex, (MHC), which is situated on the surface of the antigenpresenting cells., B-cells ingest the foreign bodies by means of, pinocytosis. Role of B cells as antigen-presenting cells, in the body is not fully understood., MHC and HLA, Major histocompatibility complex (MHC) is a large molecule present in the short arm of chromosome 6. It is made, up of a group of genes which are involved in immune, system. It has more than 200 genes including HLA, genes. HLA is made up of genes with small molecules. It, encodes antigen-presenting proteins on the cell surface., Though MHC molecules and HLA genes are distinct, terms, both are used interchangeably. Particularly in, human, the MHC molecules are often referred as HLA
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Chapter 17 t Immunity 111, molecules. MHC molecules in human beings are divided, into two types:, 1. Class I MHC molecule: It is found on every cell, in human body. It is specifically responsible for, presentation of endogenous antigens (antigens, produced intracellularly such as viral proteins and, tumor antigens) to cytotoxic T cells., 2. Class II MHC molecule: It is found on B cells,, macrophages and other antigen-presenting cells. It, is responsible for presenting the exogenous antigens, (antigens of bacteria or viruses which are engulfed, by antigen-presenting cells) to helper T cells., , 5. Simultaneously, the antigen which is bound to class II, MHC molecules activates the B cells also, resulting in, the development of humoral immunity (see below)., ROLE OF HELPER T CELLS, Helper T cells (CD4 cells) which enter the circulation, activate all the other T cells and B cells. Normal, CD4, count in healthy adults varies between 500 and 1500 per, cubic millimeter of blood., Helper T cells are of two types:, 1. Helper-1 (TH1) cells, 2. Helper-2 (TH2) cells., , Presentation of Antigen, Antigen-presenting cells present their class II MHC, molecules together with antigen-bound HLA to the helper, T cells. This activates the helper T cells through series of, events (Fig. 17.2)., Sequence of Events during Activation, of Helper T cells, 1. Helper T cell recognizes the antigen displayed on, the surface of the antigen-presenting cell with the, help of its own surface receptor protein called T cell, receptor., 2. Recognition of the antigen by the helper T cell, initiates a complex interaction between the helper T, cell receptor and the antigen. This reaction activates, helper T cells., 3. At the same time, macrophages (the antigen-presenting cells) release interleukin-1, which facilitates the, activation and proliferation of helper T cells., 4. Activated helper T cells proliferate and the proliferated cells enter the circulation for further actions., , Role of TH1 Cells, TH1 cells are concerned with cellular immunity and, secrete two substances:, i. Interleukin-2, which activates the other T cells., ii. Gamma interferon, which stimulates the phagocytic activity of cytotoxic cells, macrophages and, natural killer (NK) cells., Role of TH2 Cells, TH2 cells are concerned with humoral immunity and, secrete interleukin-4 and interleukin-5, which are concerned with:, i. Activation of B cells., ii. Proliferation of plasma cells., iii. Production of antibodies by plasma cell., ROLE OF CYTOTOXIC T CELLS, Cytotoxic T cells that are activated by helper T cells,, circulate through blood, lymph and lymphatic tissues, and destroy the invading organisms by attacking them, directly., Mechanism of Action of Cytotoxic T Cells, 1. Receptors situated on the outer membrane of cytotoxic T cells bind the antigens or organisms tightly, with cytotoxic T cells., 2. Then, the cytotoxic T cells enlarge and release cytotoxic substances like the lysosomal enzymes., 3. These substances destroy the invading organisms., 4. Like this, each cytotoxic T cell can destroy a large, number of microorganisms one after another., , FIGURE 17.2: Antigen presentation. The antigen-presenting, cells present their class II MHC molecules together with, antigen-bound HLA to the helper T cells. MHC = Major, histocompatiblility complex. HLA = Human leukocyte antigen., , Other Actions of Cytotoxic T Cells, 1. Cytotoxic T cells also destroy cancer cells, transplanted cells, such as those of transplanted heart or, kidney or any other cells, which are foreign bodies.
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112 Section 2 t Blood and Body Fluids, 2. Cytotoxic T cells destroy even body’s own tissues, which are affected by the foreign bodies, particularly, the viruses. Many viruses are entrapped in the, membrane of affected cells. The antigen of the, viruses attracts the T cells. And the cytotoxic T cells, kill the affected cells also along with viruses. Because, of this, the cytotoxic T cell is called killer cell., ROLE OF SUPPRESSOR T CELLS, Suppressor T cells are also called regulatory T cells., These T cells suppress the activities of the killer T cells., Thus, the suppressor T cells play an important role in, preventing the killer T cells from destroying the body’s, own tissues along with invaded organisms. Suppressor, cells suppress the activities of helper T cells also., ROLE OF MEMORY T CELLS, Some of the T cells activated by an antigen do not enter, the circulation but remain in lymphoid tissue. These T, cells are called memory T cells., In later periods, the memory cells migrate to various, lymphoid tissues throughout the body. When the body, is exposed to the same organism for the second time,, the memory cells identify the organism and immediately, activate the other T cells. So, the invading organism is, destroyed very quickly. The response of the T cells is, also more powerful this time., SPECIFICITY OF T CELLS, Each T cell is designed to be activated only by one type, of antigen. It is capable of developing immunity against, that antigen only. This property is called the specificity, of T cells., , DEVELOPMENT OF HUMORAL IMMUNITY, INTRODUCTION, Humoral immunity is defined as the immunity mediated, by antibodies, which are secreted by B lymphocytes., B lymphocytes secrete the antibodies into the blood, and lymph. The blood and lymph are the body fluids, (humours or humors in Latin). Since the B lymphocytes, provide immunity through humors, this type of immunity, is called humoral immunity or B cell immunity., Antibodies are the gamma globulins produced by B, lymphocytes. These antibodies fight against the invading, organisms. The humoral immunity is the major defense, mechanism against the bacterial infection., As in the case of cell-mediated immunity, the, macrophages and other antigen-presenting cells play an, , important role in the development of humoral immunity, also., ROLE OF ANTIGEN-PRESENTING CELLS, The ingestion of foreign organisms and digestion of, their antigen by the antigen-presenting cells are already, explained., Presentation of Antigen, Antigen-presenting cells present the antigenic products, bound with HLA (which is present in class II MHC, molecule) to B cells. This activates the B cells through, series of events., Sequence of Events during Activation of B Cells, 1. B cell recognizes the antigen displayed on the, surface of the antigen-presenting cell, with the help, of its own surface receptor protein called B cell, receptor., 2. Recognition of the antigen by the B cell initiates a, complex interaction between the B cell receptor and, the antigen. This reaction activates B cells., 3. At the same time, macrophages (the antigen-presenting cells) release interleukin-1, which facilitates the, activation and proliferation of B cells., 4. Activated B cells proliferate and the proliferated cells, carry out the further actions., 5. Simultaneously, the antigen bound to class II MHC, molecules activates the helper T cells, also resulting, in development of cell-mediated immunity (already, explained)., Transformation B Cells, Proliferated B cells are transformed into two types of, cells:, 1. Plasma cells, 2. Memory cells., ROLE OF PLASMA CELLS, Plasma cells destroy the foreign organisms by producing, the antibodies. Antibodies are globulin in nature., The rate of the antibody production is very high, i.e., each plasma cell produces about 2000 molecules of, antibodies per second. The antibodies are also called, immunoglobulins., Antibodies are released into lymph and then transported into the circulation. The antibodies are produced, until the end of lifespan of each plasma cell, which may, be from several days to several weeks.
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Chapter 17 t Immunity 113, ROLE OF MEMORY B CELLS, Memory B cells occupy the lymphoid tissues throughout, the body. The memory cells are in inactive condition, until the body is exposed to the same organism for the, second time., During the second exposure, the memory cells are, stimulated by the antigen and produce more quantity, of antibodies at a faster rate, than in the first exposure., The antibodies produced during the second exposure, to the foreign antigen are also more potent than those, produced during first exposure. This phenomenon forms, the basic principle of vaccination against the infections., ROLE OF HELPER T CELLS, Helper T cells are simultaneously activated by antigen., Activated helper T cells secrete two substances called, interleukin-2 and B cell growth factor, which promote:, 1. Activation of more number of B lymphocytes., 2. Proliferation of plasma cells., 3. Production of antibodies., ANTIBODIES OR IMMUNOGLOBULINS, , heavy chain (H) and one light chain (L). The two chains, in each half are also joined by disulfide bonds (S – S)., The disulfide bonds allow the movement of amino acid, chains. In each antibody, the light chain is parallel to one, end of the heavy chain. The light chain and the part of, heavy chain parallel to it form one arm. The remaining, part of the heavy chain forms another arm. A hinge joins, both the arms (Fig. 17.3)., Each chain of the antibody includes two regions:, 1. Constant region, 2. Variable region., 1. Constant Region, Amino acids present in this region are similar in number, and placement (sequence) in all the antibodies of each, type. So, this region is called constant region or Fc, (Fragment crystallizable) region. Thus, the identification, and the functions of different types of immunoglobulins, depend upon the constant region. This region binds to, the antibody receptor situated on the surface of the cell, membrane. It also causes complement fixation. So, this, region is also called the complement binding region., , An antibody is defined as a protein that is produced by B, lymphocytes in response to the presence of an antigen., Antibody is gamma globulin in nature and it is also called, immunoglobulin (Ig). Immunoglobulins form 20% of the, total plasma proteins. Antibodies enter almost all the, tissues of the body., Types of Antibodies, Five types of antibodies are identified:, 1. IgA (Ig alpha), 2. IgD (Ig delta), 3. IgE (Ig epsilon), 4. IgG (Ig gamma), 5. IgM (Ig mu)., Among these antibodies, IgG forms 75% of the, antibodies in the body., Structure of Antibodies, Antibodies are gamma globulins with a molecular weight, of 1,50,000 to 9,00,000. The antibodies are formed by, two pairs of chains, namely one pair of heavy or long, chains and one pair of light or short chains. Each heavy, chain consists of about 400 amino acids and each light, chain consists of about 200 amino acids., Actually, each antibody has two halves, which are, identical. The two halves are held together by disulfide, bonds (S–S). Each half of the antibody consists of one, , FIGURE 17.3: Structure of antibody (IgG) molecule. VL =, Variable region of light chain, VH = Variable region of heavy, chain, CL = Constant region of light chain, CH1, CH2 and CH3 =, Constant regions of heavy chains.
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114 Section 2 t Blood and Body Fluids, 2. Variable Region, Variable region is smaller compared to constant region., Amino acids occupying this region are different in, number and placement (sequence) in each antibody., So, it is called the variable region. This region enables, the antibody to recognize the specific antigen and to, bind itself with the antigen. So, this region of the chain is, called antigen-binding region or Fab (Fragment antigen, binding) region., Functions of Different Antibodies, 1. IgA plays a role in localized defense mechanism in, external secretions like tear, 2. IgD is involved in recognition of the antigen by B, lymphocytes, 3. IgE is involved in allergic reactions, 4. IgG is responsible for complement fixation, 5. IgM is also responsible for complement fixation., Mechanism of Actions of Antibodies, Antibodies protect the body from invading organisms in, two ways (Fig. 17.4):, 1. By direct actions, 2. Through complement system., 1. Direct Actions of Antibodies, Antibodies directly inactivate the invading organism by, any one of the following methods:, i. Agglutination: In this, the foreign bodies like, RBCs or bacteria with antigens on their surfaces, are held together in a clump by the antibodies., ii. Precipitation: In this, the soluble antigens like, tetanus toxin are converted into insoluble forms, and then precipitated., iii. Neutralization: During this, the antibodies cover, the toxic sites of antigenic products., iv. Lysis: It is done by the most potent antibodies., These antibodies rupture the cell membrane of, the organisms and then destroy them., 2. Actions of Antibodies through, Complement System, The indirect actions of antibodies are stronger than the, direct actions and play more important role in defense, mechanism of the body than the direct actions., Complement system is the one that enhances or, accelerates various activities during the fight against, the invading organisms. It is a system of plasma, enzymes, which are identified by numbers from C1 to, , C9. Including the three subunits of C1 (C1q C1r C1s), there, are 11 enzymes in total. Normally, these enzymes are in, inactive form and are activated in three ways:, a. Classical pathway, b. Lectin pathway, c. Alternate pathway., a. Classical pathway, In this the C1 binds with the antibodies and triggers a, series of events in which other enzymes are activated, in sequence. These enzymes or the byproducts formed, during these events produce the following activities:, i. Opsonization: Activation of neutrophils and macrophages to engulf the bacteria, which are bound, with a protein in the plasma called opsonin., ii. Lysis: Destruction of bacteria by rupturing the, cell membrane., iii. Chemotaxis: Attraction of leukocytes to the site, of antigen-antibody reaction., iv. Agglutination: Clumping of foreign bodies like, RBCs or bacteria., v. Neutralization: Covering the toxic sites of, antigenic products., vi. Activation of mast cells and basophils, which, liberate histamine: Histamine dilates the blood, vessels and increases capillary permeability., So, plasma proteins from blood enter the tissues, and inactivate the antigenic products., b. Lectin pathway, Lectin pathway occurs when mannose-binding lectin, (MBL), which is a serum protein binds with mannose or, fructose group on wall of bacteria, fungi or virus., c. Alternate pathway, Complementary system is also activated by another way,, which is called alternate pathway. It is due to a protein in, circulation called factor I. It binds with polysaccharides, present in the cell membrane of the invading organisms., This binding activates C3 and C5, which ultimately attack, the antigenic products of invading organism., Specificity of B Lymphocytes, Each B lymphocyte is designed to be activated only, by one type of antigen. It is also capable of producing, antibodies against that antigen only. This property of, B lymphocyte is called specificity. In lymphoid tissues,, the lymphocytes, which produce a specific antibody, are, together called the clone of lymphocytes.
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Chapter 17 t Immunity 115, , FIGURE 17.4: Mechanism of action of immunoglobulins, , NATURAL KILLER CELL, Natural killer (NK) cell is a large granular cell that plays, an important role in defense mechanism of the body. It, has an indented nucleus. Considered as the third type of, lymphocyte, it is often called the non-T, non-B cell. It is, derived from bone marrow. NK cell is said to be the first, line of defense in specific immunity, particularly against, viruses., NK cell kills the invading organisms or the cells of, the body without prior sensitization. It is not a phagocytic, cell but its granules contain hydrolytic enzymes such as, perforins and granzymes. These hydrolytic enzymes, play an important role in the lysis of cells of invading, organisms., , 4. Secretes cytokines such as interleukin-2, interferons,, colony stimulating factor (GM-CSF) and tumor, necrosis factor-α. Cytokines are explained later in, this chapter., , CYTOKINES, Cytokines are the hormone-like small proteins acting, as intercellular messengers (cell signaling molecules), by binding to specific receptors of target cells. These, non-antibody proteins are secreted by WBCs and some, other types of cells. Their major function is the activation, and regulation of general immune system of the body., Cytokines are distinct from the other cell-signaling, molecules such as growth factors (Chapter 1) and, hormones (Chapter 65)., , Functions of Natural Killer (NK) Cell, Natural killer cell:, 1. Destroys the viruses, 2. Destroys the viral infected or damaged cells, which, might form tumors, 3. Destroys the malignant cells and prevents development of cancerous tumors, , TYPES OF CYTOKINES, Depending upon the source of secretion and effects,, cytokines are classified into several types:, 1. Interleukins, 2. Interferons, 3. Tumor necrosis factors
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116 Section 2 t Blood and Body Fluids, 4., 5., 6., 7., , Chemokines, Defensins, Cathelicidins, Platelet-activating factor., Source of secretion and actions of these cytokines, are given in Table 17.2., 1. Interleukins, Interleukins (IL) are the polypeptide cytokines which, are produced mainly by the leukocytes and act on other, leukocytes., , 7. Platelet-activating Factor, Platelet-activating factor (PAF) accelerates agglutination, and aggregation of platelets., , IMMUNIZATION, Immunization is defined as the procedure by which the, body is prepared to fight against a specific disease. It is, used to induce the immune resistance of the body to a, specific disease. Immunization is of two types:, 1. Passive immunization, 2. Active immunization., , Types of interleukins, So far, about 16 types of interleukins are identified. IL-1,, IL-2, IL-3, IL-4, IL-5, IL-6 and IL-8 play important role, in the process of immunity. Recently IL-12 (otherwise, called natural killer cell stimulatory factor) and IL-11 are, also considered as important cytokines., 2. Interferons, Interferons (IFN) are the glycoprotein molecules. These, cytokines are considered as antiviral agents., Types of interferons, Interferons are of three types namely, INF-α, INF-β and, INF-γ., 3. Tumor Necrosis Factors, Tumor necrosis factors (TNF) are of three types, TNF-α, (cachectin), TNF-β (lymphotoxin) and TNF-γ., 4. Chemokines, Cytokines having chemoattractant action are called, chemokines., 5. Defensins, Defensins are the antimicrobial peptides., Types of defensins, Two types of defensins are identified in human:, i. α-defensins, secreted by neutrophils, macrophages and paneth cells in small intestine., ii. β-defensins, secreted by airway epithelial cells, (respiratory tract), salivary glands and cutaneous, cells., 6. Cathelicidins, Cathelicidins are also the antimicrobial peptides which, play an important role in a wide range of antimicrobial, activity in air passage and lungs., , PASSIVE IMMUNIZATION, Passive immunization or immunity is produced without, challenging the immune system of the body. It is done, by administration of serum or gamma globulins from, a person who is already immunized (affected by the, disease) to a non-immune person., Passive immunization is acquired either naturally or, artificially., Passive Natural Immunization, Passive natural immunization is acquired from the, mother before and after birth. Before birth, immunity is, transferred from mother to the fetus in the form of maternal antibodies (mainly IgG) through placenta. After birth,, the antibodies (IgA) are transferred through breast milk., Lymphocytes of the child are not activated. In, addition, the antibodies received from the mother are, metabolized soon. Therefore, the passive immunity, is short lived. The significance of passive immunity, that is obtained before birth is the prevention of Rh, incompatibility in pregnancy., Passive Artificial Immunization, Passive artificial immunization is developed by injecting, previously prepared antibodies using serum from humans, or animals. Antibodies are obtained from the persons, affected by the disease or from animals, particularly, horses which have been immunized artificially. The serum, containing the antibody (antiserum) is administered to, people who have developed the disease (therapeutic)., It is also used as a prophylactic measure. Prophylaxis, refers to medical or public health procedures to prevent, a disease in people who may be exposed to the disease, in a later period., This type of immunity is useful for providing immediate protection against acute infections like tetanus,, measles, diphtheria, etc. and for poisoning by insects,, snakes and venom from other animals. It is also used, as a prophylactic measure. However, this may result
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Chapter 17 t Immunity 117, TABLE 17.2: Cytokines, Cytokine, , Source of secretion, T cells, B cells, Eosinophils, Basophils, Monocytes, Mast cells, Macrophages, NK cells, , Action, , Interleukins, , 1., 2., 3., 4., 5., 6., 7., 8., , Interferons, , 1. WBCs, 2. NK cells, 3. Fibroblasts, , 1. Fighting against viral infection by suppressing virus, multiplication in target cells, 2. Inhibition of multiplication of parasites and cancer cells, 3. Promotion of phagocytosis by monocytes and macrophages, 4. Activation of NK cells, , Tumor necrosis factors, , 1., 2., 3., 4., 5., 6., , T cells, B cells, Mast cells, Macrophages, NK cells, Platelets, , 1., 2., 3., 4., , Chemokines, , 1., 2., 3., 4., , T cells, B cells, Monocytes, Macrophages, , Defensins, , 1. Neutrophils, 2. Macrophages, 3. Paneth cells in small, intestine, 4. Airway epithelial cells, 5. Salivary glands, 6. Cutaneous cells, , Cathelicidins, , 1., 2., 3., 4., , Platelet-activating, factor, , 1. Neutrophils, 2. Monocytes, , Neutrophils, Macrophages, Airway epithelial cells, Macrophages, , 1. Activation of T cells, macrophages and natural killer (NK) cells, 2. Promotion of growth of hemopoietic cells and B cells, 3. Acceleration of inflammatory response by activating, eosinophils, 4. Chemotaxis of neutrophils, eosinophils, basophils and T cells, 5. Destruction of invading organisms, , Causing necrosis of tumor, Activation of general immune system, Production of vascular effects, Promotion of inflammation, , Attraction of WBCs by chemotaxis, , 1., 2., 3., 4., 5., , Role in innate immunity in airway surface and lungs, Killing the phagocytozed bacteria, Antiinflammatory actions, Promotion of wound healing, Attraction of monocytes and T cells by chemotaxis, , Antimicrobial activity in air passage and lungs, , Acceleration of agglutination and aggregation of platelets, , in complications and anaphylaxis. There is a risk of, transmitting HIV and hepatitis., , Clinical infection, , Active immunization or immunity is acquired by activating, immune system of the body. Body develops resistance, against disease by producing antibodies following the, exposure to antigens. Active immunity is acquired either, naturally or artificially., , Clinical infection is defined as the invasion of the body, tissues by pathogenic microorganisms which reproduce,, multiply and cause disease by injuring the cells, secreting, a toxin or antigen-antibody reaction. During infection, the, plasma cells produce immunoglobulins to destroy the, invading antigens. Later, due to the activity of memory, cells, body retains the ability to produce the antibodies, against the specific antigens invaded previously., , Active Natural Immunization, , Subclinical infection, , Naturally acquired active immunity involves activation of, immune system in the body to produce antibodies. It is, achieved in both clinical and subclinical infections., , Subclinical infection is defined as an infection in which, symptoms are very mild and do not alert the affected, subject. The disease thus produced may not be severe, , ACTIVE IMMUNIZATION
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118 Section 2 t Blood and Body Fluids, to develop any manifestations. However, it causes the, activation of B lymphocytes, resulting in production of, antibodies., Active Artificial Immunization, Active artificial immunization is a type of immunization is, achieved by the administration of vaccines or toxoids., Vaccines, Vaccine is a substance that is introduced into the body, to prevent the disease produced by certain pathogens., Vaccine consists of dead pathogens or live but attenuated, (artificially weakened) organisms. The vaccine induces, immunity against the pathogen, either by production of, antibodies or by activation of T lymphocytes., Edward Jenner produced first live vaccine. He, produced the vaccine for smallpox from cowpox virus., Nowadays, vaccines are used to prevent many diseases, like measles, mumps, poliomyelitis, tuberculosis,, smallpox, rubella, yellow fever, rabies, typhoid, influenza,, hepatitis B, etc., Toxoids, Toxoid is a substance which is normally toxic and has, been processed to destroy its toxicity but retains its, capacity to induce antibody production by immune, system. Toxoid consists of weakened components or, toxins secreted by the pathogens. Toxoids are used, to develop immunity against diseases like diphtheria,, tetanus, cholera, etc., The active artificial immunity may be effective lifelong or for short period. It is effective lifelong against, the diseases such as mumps, measles, smallpox,, tuberculosis and yellow fever. It is effective only for short, period against some diseases like cholera (about 6, months) and tetanus (about 1 year)., , IMMUNE DEFICIENCY DISEASES, Immune deficiency diseases are a group of diseases in, which some components of immune system is missing, or defective. Normally, the defense mechanism protects, the body from invading pathogenic organism. When the, defense mechanism fails or becomes faulty (defective),, the organisms of even low virulence produce severe, disease. The organisms, which take advantage of, defective defense mechanism, are called opportunists., Immune deficiency diseases caused by such, opportunists are of two types:, 1. Congenital immune deficiency diseases, 2. Acquired immune deficiency diseases., , CONGENITAL IMMUNE DEFICIENCY DISEASES, Congenital diseases are inherited and occur due to, the defects in B cell or T cell or both. The common, examples are DiGeorge syndrome (due to absence of, thymus) and severe combined immune deficiency (due, to lymphopenia or the absence of lymphoid tissue)., ACQUIRED IMMUNE DEFICIENCY DISEASES, Acquired immune deficiency diseases occur due to, infection by some organisms. The most common disease, of this type is acquired immune deficiency syndrome, (AIDS)., Acquired Immune Deficiency Syndrome (AIDS), AIDS is an infectious disease caused by immune, deficiency virus (HIV). A person is diagnosed with, AIDS when the CD4 count is below 200 cells per cubic, millimeter of blood., AIDS is the most common problem throughout, the world because of rapid increase in the number of, victims. Infection occurs when a glycoprotein from HIV, binds to surface receptors of T lymphocytes, monocytes,, macrophages and dendritic cells leading to the destruction, of these cells. It causes slow progressive decrease in, immune function, resulting in opportunistic infections, of various types. The common opportunistic infections,, which kill the AIDS patient are pneumonia (Pneumocystis, carinii) and malignant skin cancer (Kaposi sarcoma)., These diseases are also called AIDS-related diseases., After entering the body of the host, the HIV activates, the enzyme called reverse transcriptase. HIV utilizes this, enzyme and converts its own viral RNA into viral DNA, with the help of host cell DNA itself. Now, the viral DNA, gets incorporated into the host cell DNA and prevents, the normal activities of the host cell DNA. At the same, time, the HIV increases in number inside the host’s, body. The infected host cell ruptures and releases more, number of HIV into the bloodstream. After exposure to, HIV, no symptoms develop for several weeks. This is the, incubation period. The patient develops symptoms only, when sufficient number of infected cells is ruptured. The, common symptoms are fatigue, loss of weight, chronic, diarrhea, low-grade fever, night sweats, oral ulcers,, vaginal ulcers, etc. This phase prolongs for about three, years before the disease is diagnosed., Mode of transmission, The HIV infection spreads when secretions from the, body of infected individual come in contact with blood, of the recipient through the damaged skin or mucous, membrane. The most common ways of infection are
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Chapter 17 t Immunity 119, contaminated blood transfusion, contaminated needles, or other invasive instruments, transmission from mother, to fetus during pregnancy, transmission from mother to, child during delivery or breastfeeding and vaginal sexual, intercourse., Prevention, Prevention of AIDS is essential because the authentic, treatment for this disease has not been established so, far. Progress in the development of effective treatment is, very slow. Moreover, the maximum duration of survival, after initial infection is only about 10 to 15 years. So, it is, necessary to prevent this disease., Following safety measures should be followed to, prevent AIDS:, 1. Public must be educated about the seriousness and, prevention of the disease., 2. HIV infected persons should be educated to avoid, spreading the disease to others., 3. Blood should be screened for HIV before, transfusion., 4. Intravenous drug users should not share the, needles., 5. Pregnant women should get the blood tested for, HIV. If the mother is infected, the treatment with, zidovudine may reduce incidence of infection in, infants. The baby must be given zidovudine for 6, weeks after birth., 6. Young adults and teenagers must be informed, about the safer sex techniques and use of condoms., The need for limitation of sexual partners must be, emphasized., , AUTOIMMUNE DISEASES, Autoimmune disease is defined as a condition in which, the immune system mistakenly attacks body’s own cells, and tissues. Normally, an antigen induces the immune, response in the body. The condition in which the, immune system fails to give response to an antigen is, called tolerance. This is true with respect to body’s own, antigens that are called self antigens or autoantigens., Normally, body has the tolerance against self antigen., However, in some occasions, the tolerance fails or, becomes incomplete against self antigen. This state, is called autoimmunity and it leads to the activation of, T lymphocytes or production of autoantibodies from B, lymphocytes. The T lymphocytes (cytotoxic T cells) or, autoantibodies attack the body’s normal cells whose, surface contains the self antigen or autoantigen., Thus, the autoimmune disease is produced when, body’s normal tolerance decreases and the immune system fails to recognize the body’s own tissues as ‘self’., , Autoimmune diseases are of two types:, 1. Organ specific diseases which affect only one organ, 2. Organ nonspecific or multisystemic diseases, which, affect many organs or systems., HUMAN LEUKOCYTE ANTIGEN SYSTEM, AND AUTOIMMUNE DISEASES, Human leukocyte antigen (HLA) is a group of genes, on human chromosome 6. These genes encode the, proteins which function in the cells to transport the, antigens from within the cell towards the cell surface., HLA is the product of major histocompatilility complex., HLA system monitors the immune system in the, body (see above). The HLA molecules are recognized, by the T and B lymphocytes and hence the name called, antigens. HLA is distributed in almost all the tissues of, the body. Antibodies are directed against the tissues, possessing the HLA, leading to autoimmune diseases., Most of the autoimmune diseases are HLA linked., COMMON AUTOIMMUNE DISEASES, Common autoimmune diseases are:, 1. Insulin-dependent diabetes mellitus, 2. Myasthenia gravis, 3. Hashimoto thyroiditis, 4. Graves disease, 5. Rheumatoid arthritis., 1. Insulin-dependent Diabetes Mellitus, Insulin-dependent diabetes mellitus (IDDM) is very, common in childhood and it is due to HLA-linked, autoimmunity., Common causes for IDDM, i. Development of islet cell autoantibody against, β-cells in the islets of Langerhans in pancreas., ii. Development of antibody against insulin and, glutamic acid decarboxylase., iii. Activation of T cells against islets., Other details of IDDM are given in Chapter 69., 2. Myasthenia Gravis, This neuromuscular disease occurs due to the, development of autoantibodies against the receptors, acetylcholine in neuromuscular junction. Details of, myasthenia gravis are given in Chapter 34., 3. Hashimoto Thyroiditis, Hashimoto thyroiditis is common in the late middle-aged, women. The autoantibodies impair the activity of thyroid
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120 Section 2 t Blood and Body Fluids, follicles leading to hypothyroidism. Hypothyroidism is, explained in detail in Chapter 67., 4. Graves Disease, In some cases, the autoantibodies activate thyroid-stimulating hormone (TSH) receptors leading to hyperthyroidism. The details of this disease are given in Chapter 67., 5. Rheumatoid Arthritis, Rheumatiod arthritis is the disease due to chronic inflammation of synovial lining of joints (synovitis). The synovium, becomes thick, leading to the development of swelling, around joint and tendons. The characteristic symptoms, are pain and stiffness of joints. The chronic inflammation, occurs due to the continuous production of autoantibodies, called rheumatoid arthritis factors (RA factors)., , ALLERGY AND IMMUNOLOGICAL, HYPERSENSITIVITY REACTIONS, The term allergy means hypersensitivity. It is defined as, abnormal immune response to a chemical or physical, agent (allergen). During the first exposure to an allergen,, the immune response does not normally produce any, reaction in the body. Sensitization or an initial exposure, to the allergen is required for the reaction. So, the, subsequent exposure to the allergen causes variety of, inflammatory responses. These responses are called, allergic reactions or immunological hypersensitivity, reactions., Immunological hypersensitivity reactions may be, innate or acquired. These reactions are mediated mostly, by antibodies. In some conditions, T cells are involved., Common symptoms include sneezing, itching and skin, rashes. However, in some persons the symptoms may, be severe., Common allergic conditions are:, 1. Food allergy, 2. Allergic rhinitis, 3. Bronchial asthma, 4. Urticaria., ALLERGENS, Any substance that produces the manifestations of, allergy is called an allergen. It may be an antigen or a, protein or any other type of substance. Even physical, agents can develop allergy., Allergens are introduced by:, 1. Contact (e.g.: chemical substance), 2. Inhalation (e.g.: pollen), 3. Ingestion (e.g.: food), 4. Injection (e.g.: drug)., , Common Allergens, 1. Food substances: Wheat, egg, milk and chocolate., 2. Inhalants: Pollen grains, fungi, dust, smoke,, perfumes and disagreeable odor., 3. Contactants: Chemical substances, metals, animals, and plants., 4. Infectious agents: Parasites, bacteria, viruses and, fungi., 5. Drugs: Aspirin and antibiotics., 6. Physical agents: Cold, heat, light, pressure and, radiation., IMMUNOLOGICAL HYPERSENSITIVE, REACTIONS, Immunological hypersensitive reactions to an agent, give rise to several allergic conditions and autoimmune, diseases., Hypersensitive reactions are classified into five, types:, Type I or anaphylactic reactions., Type II or cytotoxic reactions., Type III or antibody-mediated reactions., Type IV or cell-mediated reactions., Type V or stimulatory/blocking reactions., Type I or Anaphylactic Reactions, Anaphylaxis means exaggerated reactions of the body to, an antigen or other agents to which the body is sensitized, already. It is also called immediate hypersensitive reaction, because it develops within few minutes of exposure to, an allergen. Anaphylactic reactions are mediated by IgE, and other factors involved in inflammation (inflammation, means the protective response of the tissues to the, damage or destruction of cells)., When the body is exposed to an allergen, the IgE, immunoglobulins are produced. Also called reagins or, sensitizing antibodies, these immunoglobulins bind, with the surface receptors of mast cells and circulating, basophils. Mast cells are the granulated wandering cells, found in connective tissue and beneath the mucous, membrane in the throat, lungs and eyes., During subsequent exposure of the body to the, same allergen, the allergen IgE antibody reaction takes, place. This leads to degranulation of mast cells and, basophils, with the release of some chemical mediators, such histamine. The chemical mediators produce the, hypersensitivity reactions. Most serious reactions are, fall in blood pressure (due to vasodilatation),obstruction, of air passage and difficulty in breathing (due to, bronchoconstriction) and shock (Chapter 116).
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Chapter 17 t Immunity 121, Type II or Cytotoxic Reactions, Cytotoxic reactions involve mainly the IgG antibodies,, which bind with antigens on the surface of the cells,, particularly the blood cells. The affected cells are, destroyed. Sometimes, IgM and IgA antibodies are, also involved. The diseases developed due to cytotoxic, reactions are hemolytic diseases of newborn in case of, Rh incompatibility and autoimmune hemolytic anemia., , in contact dermatitis caused by chemical allergens and, during rejection of transplanted tissues. An example of, type IV reaction is the delayed reaction after intradermal, injection of tuberculin in persons who are previously, affected by tuberculosis (tuberculosis skin test or, Mantoux test). The important feature of delayed type, of hypersensitivity is the involvement of T lymphocytes, rather than the antibodies., Type V or Stimulatory/Blocking Reactions, , Type III or Antibody-mediated Reactions, Excess amounts of antibodies like IgG or IgM are, produced in this type. The antigen-antibody complexes, are precipitated and deposited in localized areas like, joints causing arthritis, heart causing myocarditis and, glomeruli of kidney producing glomerulonephritis., Type IV or Cell-mediated Reactions, This type of hypersensitivity is also called delayed or slow, type of hypersensitivity. It is found in allergic reactions, due to the bacteria, viruses and fungi. It is also seen, , It is seen in autoimmune diseases like Graves’ disease, (stimulatory reactions) and myasthenia gravis (blocking, reactions)., Graves’ disease: Normally, TSH combines with surface, receptors of thyroid cells and causes synthesis and, secretion of thyroid hormones. The secretion of thyroid, hormones can be increased by thyroid-stimulating, antibodies (TSAB) produced by plasma cells (B, lymphocytes). The excess secretion of thyroid hormone, leads to Graves’ disease., Myasthenia gravis: It is due to the development of IgG, autoantibodies (see above).
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Chapter, , Platelets, , , , , , , , , , , 18, , INTRODUCTION, STRUCTURE AND COMPOSITION, NORMAL COUNT AND VARIATIONS, PROPERTIES, FUNCTIONS, ACTIVATORS AND INHIBITORS, DEVELOPMENT, LIFESPAN AND FATE, APPLIED PHYSIOLOGY – PLATELET DISORDERS, , INTRODUCTION, , CELL MEMBRANE, , Platelets or thrombocytes are the formed elements of, blood. Platelets are small colorless, non-nucleated and, moderately refractive bodies. These formed elements of, blood are considered to be the fragments of cytoplasm., , Cell membrane of platelet is 6 nm thick. Extensive, invagination of cell membrane forms an open canalicular, system (Fig. 18.1). This canalicular system is a delicate, tunnel system through which the platelet granules, extrude their contents., Cell membrane of platelet contains lipids in the form, of phospholipids, cholesterol and glycolipids, carbohydrates as glycocalyx and glycoproteins and proteins., Of these substances, glycoproteins and phospholipids, are functionally important., , Size of Platelets, Diameter : 2.5 µ (2 to 4 µ), Volume : 7.5 cu µ (7 to 8 cu µ)., Shape of Platelets, Normally, platelets are of several shapes, viz. spherical, or rod-shaped and become oval or disk-shaped when, inactivated. Sometimes, the platelets have dumbbell, shape, comma shape, cigar shape or any other unusual, shape. Inactivated platelets are without processes or, filopodia and the activated platelets develop processes, or filopodia (see below)., , STRUCTURE AND COMPOSITION, Platelet is constituted by:, 1. Cell membrane or surface membrane, 2. Microtubules, 3. Cytoplasm., , Glycoproteins, Glycoproteins prevent the adherence of platelets to normal endothelium, but accelerate the adherence of platelets, to collagen and damaged endothelium in ruptured blood, vessels. Glycoproteins also form the receptors for, adenosine diphosphate (ADP) and thrombin., Phospholipids, Phospholipids accelerate the clotting reactions. The, phospholipids form the precursors of thromboxane A2, and other prostaglandin-related substances.
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Chapter 18 t Platelets 123, MICROTUBULES, Microtubules form a ring around cytoplasm below the cell, membrane. Microtubules are made up of polymerized, proteins called tubulin. These tubules provide structural, support for the inactivated platelets to maintain the disklike shape., CYTOPLASM, Cytoplasm of platelets contains the cellular organelles,, Golgi apparatus, endoplasmic reticulum, mitochondria,, microtubule, microvessels, filaments and granules., Cytoplasm also contains some chemical substances, such as proteins, enzymes, hormonal substances, etc., Proteins, 1. Contractile proteins, i. Actin and myosin: Contractile proteins, which, are responsible for contraction of platelets., ii. Thrombosthenin: Third contractile protein, which, is responsible for clot retraction., 2. von Willebrand factor: Responsible for adherence, of platelets and regulation of plasma level of factor, VIII., 3. Fibrin-stabilizing factor: A clotting factor., 4. Platelet-derived growth factor (PDGF): Responsible, for repair of damaged blood vessels and wound, healing. It is a potent mytogen (chemical agent that, promotes mitosis) for smooth muscle fibers of blood, vessels., 5. Platelet-activating factor (PAF): Causes aggregation, of platelets during the injury of blood vessels,, resulting in prevention of excess loss of blood., 6. Vitronectin (serum spreading factor): Promotes, adhesion of platelets and spreading of tissue cells in, culture., 7. Thrombospondin: Inhibits angiogenesis (formation, of new blood vessels from pre-existing vessels)., Enzymes, 1. Adensosine triphosphatase (ATPase), 2. Enzymes necessary for synthesis of prostaglandins., Hormonal Substances, 1. Adrenaline, 2. 5-hydroxytryptamine (5-HT; serotonin), 3. Histamine., Other Chemical Substances, 1. Glycogen, 2. Substances like blood group antigens, , 3. Inorganic substances such as calcium, copper,, magnesium and iron., Platelet Granules, Granules present in cytoplasm of platelets are of two, types:, 1. Alpha granules, 2. Dense granules., Substances present in these granules are given in, Table 18.1., Alpha granules, Alpha granules contain:, 1. Clotting factors – fibrinogen, V and XIII, 2. Platelet-derived growth factor, 3. Vascular endothelial growth factor (VEGF), 4. Basic fibroblast growth factor (FGF), 5. Endostatin, 6. Thrombospondin., Dense granules, Dense granules contain:, 1. Nucleotides, 2. Serotonin, 3. Phospholipid, 4. Calcium, 5. Lysosomes., , NORMAL COUNT AND VARIATIONS, Normal platelet count is 2,50,000/cu mm of blood. It ranges between 2,00,000 and 4,00,000/cu mm of blood., PHYSIOLOGICAL VARIATIONS, 1. Age: Platelets are less in infants (1,50,000 to, 2,00,000/cu mm) and reaches normal level at 3rd, month after birth., 2. Sex: There is no difference in the platelet count, between males and females. In females, it is reduced, during menstruation., 3. High altitude: Platelet count increases., 4. After meals: After taking food, the platelet count, increases., TABLE 18.1: Substances present in platelet granules, Alpha granules, Clotting factors: fibrinogen, V and XIII, Platelet-derived growth factor, Vascular endothelial growth factor, Basic fibroblast growth factor, Endostatin, Thrombospondin, , Dense granules, Nucleotides, Serotonin, Phospholipid, Calcium, Lysosomes
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124 Section 2 t Blood and Body Fluids, During activation, the platelets change their shape, with elongation of long filamentous pseudopodia which, are called processes or filopodia (Fig. 18.2)., Filopodia help the platelets aggregate together., Activation and aggregation of platelets is accelerated, by ADP, thromboxane A2 and platelet-activating factor, (PTA: cytokine secreted by neutrophils and monocytes;, Chapter 16)., AGGLUTINATION, Agglutination is the clumping together of platelets., Aggregated platelets are agglutinated by the actions of, some platelet agglutinins and platelet-activating factor., , FUNCTIONS OF PLATELETS, , FIGURE 18.1: Platelet under electron microscope, , Normally, platelets are inactive and execute their actions, only when activated. Activated platelets immediately, release many substances. This process is known as, platelet release reaction. Functions of platelets are, carried out by these substances., Functions of platelets are:, 1. ROLE IN BLOOD CLOTTING, , PATHOLOGICAL VARIATIONS, Refer applied physiology of this chapter., , PROPERTIES OF PLATELETS, Platelets have three important properties (three ‘A’s):, 1. Adhesiveness, 2. Aggregation, 3. Agglutination., ADHESIVENESS, Adhesiveness is the property of sticking to a rough, surface. During injury of blood vessel, endothelium is, damaged and the subendothelial collagen is exposed., While coming in contact with collagen, platelets are, activated and adhere to collagen. Adhesion of platelets, involves interaction between von Willebrand factor, secreted by damaged endothelium and a receptor protein, called glycoprotein Ib situated on the surface of platelet, membrane. Other factors which accelerate adhesiveness, are collagen, thrombin, ADP, Thromboxane A2, calcium, ions, P-selectin and vitronectin., , Platelets are responsible for the formation of intrinsic, prothrombin activator. This substance is responsible for, the onset of blood clotting (Chapter 20)., 2. ROLE IN CLOT RETRACTION, In the blood clot, blood cells including platelets are, entrapped in between the fibrin threads. Cytoplasm of, platelets contains the contractile proteins, namely actin,, myosin and thrombosthenin, which are responsible for, clot retraction (Chapter 20)., 3. ROLE IN PREVENTION OF, BLOOD LOSS (HEMOSTASIS), Platelets accelerate the hemostasis by three ways:, i. Platelets secrete 5-HT, which causes the constriction of blood vessels., ii. Due to the adhesive property, the platelets seal, the damage in blood vessels like capillaries., iii. By formation of temporary plug, the platelets, seal the damage in blood vessels (Chapter 19)., , AGGREGATION (GROUPING OF PLATELETS), , 4. ROLE IN REPAIR OF RUPTURED, BLOOD VESSEL, , Aggregation is the grouping of platelets. Adhesion is, followed by activation of more number of platelets by, substances released from dense granules of platelets., , Platelet-derived growth factor (PDGF) formed in cytoplasm of platelets is useful for the repair of the endothelium, and other structures of the ruptured blood vessels.
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Chapter 18 t Platelets 125, , LIFESPAN AND FATE OF PLATELETS, Average lifespan of platelets is 10 days. It varies, between 8 and 11 days. Platelets are destroyed by, tissue macrophage system in spleen. So, splenomegaly, (enlargement of spleen) decreases platelet count and, splenectomy (removal of spleen) increases platelet, count., A, , B, , FIGURE 18.2: A. Inactive platelets. B. Activated platelets., , APPLIED PHYSIOLOGY –, PLATELET DISORDERS, , ACTIVATORS AND INHIBITORS, OF PLATELETS, , Platelet disorders occur because of pathological variation, in platelet count and dysfunction of platelets., Platelet disorders are:, 1. Thrombocytopenia, 2. Thrombocytosis, 3. Thrombocythemia, 4. Glanzmann’s thrombasthenia., , ACTIVATORS OF PLATELETS, , 1. Thrombocytopenia, , 5. ROLE IN DEFENSE MECHANISM, By the property of agglutination, platelets encircle the, foreign bodies and destroy them., , 1. Collagen, which is exposed during damage of blood, vessels, 2. von Willebrand factor, 3. Thromboxane A2, 4. Platelet-activating factor, 5. Thrombin, 6. ADP, 7. Calcium ions, 8. P-selectin: Cell adhesion molecule secreted from, endothelial cells, 9. Convulxin: Purified protein from snake venom., INHIBITORS OF PLATELETS, 1., 2., 3., 4., , Nitric oxide, Clotting factors: II, IX, X, XI and XII, Prostacyclin, Nucleotidases which breakdown the ADP., , Decrease in platelet count is called thrombocytopenia. It, leads to thrombocytopenic purpura (Chapter 20)., Thrombocytopenia occurs in the following, conditions:, i. Acute infections, ii. Acute leukemia, iii. Aplastic and pernicious anemia, iv. Chickenpox, v. Smallpox, vi. Splenomegaly, vii. Scarlet fever, viii. Typhoid, ix. Tuberculosis, x. Purpura, xi. Gaucher’s disease., 2. Thrombocytosis, , DEVELOPMENT OF PLATELETS, Platelets are formed from bone marrow. Pluripotent stem, cell gives rise to the colony forming unit-megakaryocyte, (CFU-M). This develops into megakaryocyte. Cytoplasm, of megakaryocyte form pseudopodium. A portion of, pseudopodium is detached to form platelet, which enters, the circulation (Fig. 10.2)., Production of platelets is influenced by colony-stimulating factors and thrombopoietin. Colony-stimulating, factors are secreted by monocytes and T lymphocytes., Thrombopoietin is a glycoprotein like erythropoietin. It is, secreted by liver and kidneys., , Increase in platelet count is called thrombocytosis., Thrombocytosis occurs in the following conditions:, i. Allergic conditions, ii. Asphyxia, iii. Hemorrhage, iv. Bone fractures, v. Surgical operations, vi. Splenectomy, vii. Rheumatic fever, viii. Trauma (wound or injury or damage caused by, external force).
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126 Section 2 t Blood and Body Fluids, 3. Thrombocythemia, , 4. Glanzmann’s Thrombasthenia, , Thrombocythemia is the condition with persistent and, abnormal increase in platelet count. Thrombocythemia, occurs in the following conditions:, i. Carcinoma, ii. Chronic leukemia, iii. Hodgkin’s disease., , Glanzmann’s thrombasthenia is an inherited hemorrhagic disorder, caused by structural or functional abnormality of platelets. It leads to thrombasthenic purpura, (Chapter 20). However, the platelet count is normal., It is characterized by normal clotting time, normal or, prolonged bleeding time but defective clot retraction.
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Chapter, , Hemostasis, , 19, , DEFINITION, STAGES OF HEMOSTASIS, , , , , VASOCONSTRICTION, PLATELET PLUG FORMATION, COAGULATION OF BLOOD, , DEFINITION, Hemostasis is defined as arrest or stoppage of bleeding., , STAGES OF HEMOSTASIS, When a blood vessel is injured, the injury initiates a, series of reactions, resulting in hemostasis. It occurs in, three stages (Fig. 19.1):, 1. Vasoconstriction, 2. Platelet plug formation, 3. Coagulation of blood., VASOCONSTRICTION, Immediately after injury, the blood vessel constricts, and decreases the loss of blood from damaged, portion. Usually, arterioles and small arteries constrict., Vasoconstriction is purely a local phenomenon. When the, blood vessels are cut, the endothelium is damaged and, the collagen is exposed. Platelets adhere to this colla, gen and get activated. The activated platelets secrete, serotonin and other vasoconstrictor substances which, cause constriction of the blood vessels. Adherence of, , platelets to the collagen is accelerated by von Willebrand, factor. This factor acts as a bridge between a specific, glycoprotein present on the surface of platelet and, collagen fibrils., PLATELET PLUG FORMATION, Platelets get adhered to the collagen of ruptured blood, vessel and secrete adenosine diphosphate (ADP) and, thromboxane A2. These two substances attract more and, more platelets and activate them. All these platelets aggre, gate together and form a loose temporary platelet plug or, temporary hemostatic plug, which closes the ruptured, vessel and prevents further blood loss. Platelet aggrega, tion is accelerated by plateletactivating factor (PAF)., COAGULATION OF BLOOD, During this process, the fibrinogen is converted into, fibrin. Fibrin threads get attached to the loose platelet, plug, which blocks the ruptured part of blood vessels, and prevents further blood loss completely. Mechanism, of blood coagulation is explained in the next chapter.
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128 Section 2 t Blood and Body Fluids, , FIGURE 19.1: States of hemostasis. ADP = Adenosine diphosphate; PAF = Plateletactivating factor.
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Coagulation of Blood, , , , , , , , , , , , Chapter, , 20, , DEFINITION, FACTORS INVOLVED IN BLOOD CLOTTING, SEQUENCE OF CLOTTING MECHANISM, BLOOD CLOT, ANTICLOTTING MECHANISM IN THE BODY, ANTICOAGULANTS, PHYSICAL METHODS TO PREVENT BLOOD CLOTTING, PROCOAGULANTS, TESTS FOR BLOOD CLOTTING, APPLIED PHYSIOLOGY, , DEFINITION, Coagulation or clotting is defined as the process in which, blood loses its fluidity and becomes a jelly-like mass few, minutes after it is shed out or collected in a container., , FACTORS INVOLVED IN BLOOD CLOTTING, Coagulation of blood occurs through a series of, reactions due to the activation of a group of substances., Substances necessary for clotting are called clotting, factors., Thirteen clotting factors are identified:, Factor I, Fibrinogen, Factor II, Prothrombin, Factor III, Thromboplastin (Tissue factor), Factor IV, Calcium, Factor V, Labile factor (Proaccelerin or accelerator, globulin), Factor VI, Presence has not been proved, Factor VII, Stable factor, Factor VIII Antihemophilic factor (Antihemophilic, globulin), Factor IX, Christmas factor, Factor X, Stuart-Prower factor, Factor XI, Plasma thromboplastin antecedent, , Factor XII, Hageman factor (Contact factor), Factor XIII Fibrin-stabilizing factor (Fibrinase)., Clotting factors were named after the scientists who, discovered them or as per the activity, except factor, IX. Factor IX or Christmas factor was named after the, patient in whom it was discovered., , SEQUENCE OF CLOTTING MECHANISM, ENZYME CASCADE THEORY, Most of the clotting factors are proteins in the form of, enzymes. Normally, all the factors are present in the, form of inactive proenzyme. These proenzymes must, be activated into enzymes to enforce clot formation. It is, carried out by a series of proenzyme-enzyme conversion, reactions. First one of the series is converted into an, active enzyme that activates the second one, which, activates the third one; this continues till the final active, enzyme thrombin is formed., Enzyme cascade theory explains how various, reactions, involved in the conversion of proenzymes, to active enzymes take place in the form of a cascade., Cascade refers to a process that occurs through a series, of steps, each step initiating the next, until the final step, is reached.
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130 Section 2 t Blood and Body Fluids, Stages of Blood Clotting, In general, blood clotting occurs in three stages:, 1. Formation of prothrombin activator, 2. Conversion of prothrombin into thrombin, 3. Conversion of fibrinogen into fibrin., STAGE 1: FORMATION OF PROTHROMBIN, ACTIVATOR, Blood clotting commences with the formation of a, substance called prothrombin activator, which converts, prothrombin into thrombin. Its formation is initiated by, substances produced either within the blood or outside, the blood., Thus, formation of prothrombin activator occurs, through two pathways:, i. Intrinsic pathway, ii. Extrinsic pathway., i. Intrinsic Pathway for the Formation, of Prothrombin Activator, In this pathway, the formation of prothrombin activator, is initiated by platelets, which are within the blood itself, (Fig. 20.1)., Sequence of Events in Intrinsic pathway, i. During the injury, the blood vessel is ruptured., Endothelium is damaged and collagen beneath, the endothelium is exposed., ii. When factor XII (Hageman factor) comes, in contact with collagen, it is converted into, activated factor XII in the presence of kallikrein, and high molecular weight (HMW) kinogen., iii. The activated factor XII converts factor XI into, activated factor XI in the presence of HMW, kinogen., iv. The activated factor XI activates factor IX in the, presence of factor IV (calcium)., v. Activated factor IX activates factor X in the, presence of factor VIII and calcium., vi. When platelet comes in contact with collagen, of damaged blood vessel, it gets activated and, releases phospholipids., vii. Now the activated factor X reacts with platelet, phospholipid and factor V to form prothrombin, activator. This needs the presence of calcium, ions., viii. Factor V is also activated by positive feedback, effect of thrombin (see below)., , ii. Extrinsic Pathway for the Formation, of Prothrombin Activator, In this pathway, the formation of prothrombin activator, is initiated by the tissue thromboplastin, which is formed, from the injured tissues., Sequence of Events in Extrinsic Pathway, i. Tissues that are damaged during injury release, tissue thromboplastin (factor III). Thromboplastin, contains proteins, phospholipid and glycoprotein,, which act as proteolytic enzymes., ii. Glycoprotein and phospholipid components of, thromboplastin convert factor X into activated, factor X, in the presence of factor VII., iii. Activated factor X reacts with factor V and, phospholipid component of tissue thromboplastin, to form prothrombin activator. This reaction, requires the presence of calcium ions., STAGE 2: CONVERSION OF PROTHROMBIN, INTO THROMBIN, Blood clotting is all about thrombin formation. Once, thrombin is formed, it definitely leads to clot formation., Sequence of Events in Stage 2, i. Prothrombin activator that is formed in intrinsic, and extrinsic pathways converts prothrombin, into thrombin in the presence of calcium (factor, IV)., ii. Once formed thrombin initiates the formation of, more thrombin molecules. The initially formed, thrombin activates Factor V. Factor V in turn, accelerates formation of both extrinsic and, intrinsic prothrombin activator, which converts, prothrombin into thrombin. This effect of thrombin, is called positive feedback effect (Fig. 20.1)., STAGE 3: CONVERSION OF FIBRINOGEN, INTO FIBRIN, The final stage of blood clotting involves the conversion, of fibrinogen into fibrin by thrombin., Sequence of Events in Stage 3, i. Thrombin converts inactive fibrinogen into, activated fibrinogen due to loss of 2 pairs of
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Chapter 20 t Coagulation of Blood 131, , FIGURE 20.1: Stages of blood coagulation. a = Activated, + = Thrombin induces formation of more thrombin, (positive feedback); HMW = High molecular weight., , polypeptides from each fibrinogen molecule. The, activated fibrinogen is called fibrin monomer., ii. Fibrin monomer polymerizes with other monomer, molecules and form loosely arranged strands of, fibrin., , iii. Later these loose strands are modified into dense, and tight fibrin threads by fibrin-stabilizing factor, (factor XIII) in the presence of calcium ions (Fig., 20.1). All the tight fibrin threads are aggregated, to form a meshwork of stable clot.
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132 Section 2 t Blood and Body Fluids, , BLOOD CLOT, DEFINITION AND COMPOSITION OF CLOT, Blood clot is defined as the mass of coagulated blood, which contains RBCs, WBCs and platelets entrapped in, fibrin meshwork., RBCs and WBCs are not necessary for clotting, process. However, when clot is formed, these cells are, trapped in it along with platelets. The trapped RBCs are, responsible for the red color of the clot., The external blood clot is also called scab. It adheres, to the opening of damaged blood vessel and prevents, blood loss., , 2. Thrombomodulin combines with thrombin and forms, a thrombomodulin-thrombin complex, 3. Thrombomodulin-thrombin, complex, activates, protein C, 4. Activated protein C inactivates factor V and VIII in, the presence of a cofactor called protein S, 5. Protein C also inactivates the t-PA inhibitor, 6. Now, the t-PA becomes active, 7. Activated t-PA and lysosomal enzymes activate, plasminogen to form plasmin. Plasminogen is also, activated by thrombin and u-PA (Fig. 20.2)., , CLOT RETRACTION, After the formation, the blood clot starts contracting. And, after about 30 to 45 minutes, the straw-colored serum, oozes out of the clot. The process involving the contraction, of blood clot and oozing of serum is called clot retraction., Contractile proteins, namely actin, myosin and, thrombosthenin in the cytoplasm of platelets are, responsible for clot retraction., FIBRINOLYSIS, Lysis of blood clot inside the blood vessel is called, fibrinolysis. It helps to remove the clot from lumen of the, blood vessel. This process requires a substance called, plasmin or fibrinolysin., Formation of Plasmin, Plasmin is formed from inactivated glycoprotein called, plasminogen. Plasminogen is synthesized in liver, and it is incorporated with other proteins in the blood, clot. Plasminogen is converted into plasmin by tissue, plasminogen activator (t-PA), lysosomal enzymes and, thrombin. The t-PA and lysosomal enzymes are released, from damaged tissues and damaged endothelium., Thrombin is derived from blood. The t-PA is always, inhibited by a substance called t-PA inhibitor. It is also, inhibited by factors V and VIII., Besides t-PA, there is another plasminogen activator, called urokinase plasminogen activator (u-PA). It is, derived from blood., Sequence of Events Involved in the, Activation of Plasminogen, 1. During intravascular clotting, the endothelium of the, blood vessel secretes a thrombin-binding protein, the, thrombomodulin. It is secreted by the endothelium, of all the blood vessels, except the minute vessels, of brain., , FIGURE 20.2: Fibrinolysis. t-PA = Tissue plasminogen, activator, u-PA = Urokinase plasminogen activator.
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Chapter 20 t Coagulation of Blood 133, , ANTICLOTTING MECHANISM IN THE BODY, , Mechanism of Action of Heparin, , Under physiological conditions, intravascular clotting, does not occur. It is because of the presence of some, physicochemical factors in the body., , Heparin:, , 1. Physical Factors, i. Continuous circulation of blood., ii. Smooth endothelial lining of the blood vessels., 2. Chemical Factors – Natural Anticoagulants, i. Presence of natural anticoagulant called heparin, that is produced by the liver, ii. Production of thrombomodulin by endothelium, of the blood vessels (except in brain capillaries)., Thrombomodulin is a thrombin-binding protein., It binds with thrombin and forms a thrombomodulin-thrombin complex. This complex activates protein C. Activated protein C along with, its cofactor protein S inactivates Factor V and, Factor VIII. Inactivation of these two clotting, factors prevents clot formation, iii. All the clotting factors are in inactive state., , ANTICOAGULANTS, Substances which prevent or postpone coagulation of, blood are called anticoagulants., Anticoagulants are of three types:, 1. Anticoagulants used to prevent blood clotting inside, the body, i.e. in vivo., 2. Anticoagulants used to prevent clotting of blood that, is collected from the body, i.e. in vitro., 3. Anticoagulants used to prevent blood clotting both in, vivo and in vitro., 1. HEPARIN, Heparin is a naturally produced anticoagulant in the body., It is produced by mast cells which are the wandering, cells present immediately outside the capillaries in many, tissues or organs that contain more connective tissue., These cells are abundant in liver and lungs. Basophils, also secrete heparin., Heparin is a conjugated polysaccharide. Commercial, heparin is prepared from the liver and other organs of, animals. Commercial preparation is available in liquid, form or dry form as sodium, calcium, ammonium or, lithium salts., , i. Prevents blood clotting by its antithrombin, activity. It directly suppresses the activity of, thrombin, ii. Combines with antithrombin III (a protease, inhibitor present in circulation) and removes, thrombin from circulation, iii. Activates antithrombin III, iv. Inactivates the active form of other clotting, factors like IX, X, XI and XII (Fig. 20.3)., Uses of Heparin, Heparin is used as an anticoagulant both in vivo and in, vitro., Clinical use, Intravenous injection of heparin (0.5 to 1 mg/kg body, weight) postpones clotting for 3 to 4 hours (until it is, destroyed by the enzyme heparinase). So, it is widely, used as an anticoagulant in clinical practice. In clinics,, heparin is used for many purposes such as:, i. To prevent intravascular blood clotting during, surgery., ii. While passing the blood through artificial kidney, for dialysis., iii. During cardiac surgery, which involves heartlung machine., iv. To preserve the blood before transfusion., Use in the laboratory, Heparin is also used as anticoagulant in vitro while, collecting blood for various investigations. About 0.1 to, 0.2 mg is sufficient for 1 mL of blood. It is effective for 8, to 12 hours. After that, blood will clot because heparin, only delays clotting and does not prevent it., Heparin is the most expensive anticoagulant., 2. COUMARIN DERIVATIVES, Warfarin and dicoumoral are the derivatives of coumarin., Mechanism of Action, Coumarin derivatives prevent blood clotting by inhibiting, the action of vitamin K. Vitamin K is essential for the, formation of various clotting factors, namely II, VII, IX, and X.
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134 Section 2 t Blood and Body Fluids, 4. OXALATE COMPOUNDS, Oxalate compounds prevent coagulation by forming, calcium oxalate, which is precipitated later. Thus, these, compounds reduce the blood calcium level., Earlier sodium and potassium oxalates were, used. Nowadays, mixture of ammonium oxalate and, potassium oxalate in the ratio of 3 : 2 is used. Each, salt is an anticoagulant by itself. But potassium oxalate, alone causes shrinkage of RBCs. Ammonium oxalate, alone causes swelling of RBCs. But together, these, substances do not alter the cellular activity., Mechanism of Action, Oxalate combines with calcium and forms insoluble, calcium oxalate. Thus, oxalate removes calcium from, blood and lack of calcium prevents coagulation., Uses, FIGURE 20.3: Mechanism of action of heparin, , Oxalate compounds are used only as in vitro, anticoagulants. 2 mg of mixture is necessary for 1 ml, of blood. Since oxalate is poisonous, it cannot be used, in vivo., , Uses, Dicoumoral and warfarin are the commonly used oral, anticoagulants (in vivo). Warfarin is used to prevent, myocardial infarction (heart attack), strokes and, thrombosis., 3. EDTA, Ethylenediaminetetraacetic acid (EDTA) is a strong, anticoagulant. It is available in two forms:, i. Disodium salt (Na2 EDTA)., ii. Tripotassium salt (K3 EDTA)., Mechanism of Action, These substances prevent blood clotting by removing, calcium from blood., Uses, EDTA is used as an anticoagulant both in vivo and in, vitro. It is:, i. Commonly administered intravenously, in cases, of lead poisoning., ii. Used as an anticoagulant in the laboratory (in, vitro). 0.5 to 2.0 mg of EDTA per mL of blood, is sufficient to preserve the blood for at least 6, hours. On refrigeration, it can preserve the blood, up to 24 hours., , 5. CITRATES, Sodium, ammonium and potassium citrates are used as, anticoagulants., Mechanism of Action, Citrate combines with calcium in blood to form insoluble, calcium citrate. Like oxalate, citrate also removes calcium, from blood and lack of calcium prevents coagulation., Uses, Citrate is used as in vitro anticoagulant., i. It is used to store blood in the blood bank as:, a. Acid citrate dextrose (ACD): 1 part of ACD, with 4 parts of blood, b. Citrate phosphate dextrose (CPD): 1 part of, CPD with 4 parts of blood, ii. Citrate is also used in laboratory in the form of, formol-citrate solution (Dacie’s solution) for RBC, and platelet counts., OTHER SUBSTANCES WHICH PREVENT, BLOOD CLOTTING, Peptone, C-type lectin (proteins from venom of, viper snake) and hirudin (from the leach Hirudinaria, manillensis) are the known anticoagulants.
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Chapter 20 t Coagulation of Blood 135, , PHYSICAL METHODS TO PREVENT, BLOOD CLOTTING, Coagulation of blood is postponed or prevented by the, following physical methods:, COLD, Reducing the temperature to about 5°C postpones the, coagulation of blood., COLLECTING BLOOD IN A CONTAINER, WITH SMOOTH SURFACE, Collecting the blood in a container with smooth surface, like a silicon-coated container prevents clotting. The, smooth surface inhibits the activation of factor XII and, platelets. So, the formation of prothrombin activator is, prevented., , PROCOAGULANTS, Procoagulants or hemostatic agents are the substances, which accelerate the process of blood coagulation., Procoagulants are:, , 1., 2., 3., 4., 5., 6., , Bleeding time, Clotting time, Prothrombin time, Partial prothrombin time, International normalized ratio, Thrombin time., , BLEEDING TIME, Bleeding time (BT) is the time interval from oozing of, blood after a cut or injury till arrest of bleeding. Usually,, it is determined by Duke method using blotting paper or, filter paper method. Its normal duration is 3 to 6 minutes., It is prolonged in purpura., CLOTTING TIME, Clotting time (CT) is the time interval from oozing of, blood after a cut or injury till the formation of clot. It is, usually determined by capillary tube method. Its normal, duration is 3 to 8 minutes. It is prolonged in hemophilia., PROTHROMBIN TIME, , SODIUM OR CALCIUM ALGINATE, , Prothrombin time (PT) is the time taken by blood to, clot after adding tissue thromboplastin to it. Blood is, collected and oxalated so that, the calcium is precipitated, and prothrombin is not converted into thrombin. Thus,, the blood clotting is prevented. Then a large quantity, of tissue thromboplastin with calcium is added to this, blood. Calcium nullifies the effect of oxalate. The tissue, thromboplastin activates prothrombin and blood clotting, occurs., During this procedure, the time taken by blood to, clot after adding tissue thromboplastin is determined., Prothrombin time indicates the total quantity of, prothrombin present in the blood., Normal duration of prothrombin time is 10 to 12, seconds. It is prolonged in deficiency of prothrombin and, other factors like factors I, V, VII and X. However, it is, normal in hemophilia., , Sosium or calcium alginate substances enhance blood, clotting process by activating the Hageman factor., , PARTIAL PROTHROMBIN TIME OR, ACTIVATED PROTHROMBIN TIME, , THROMBIN, Thrombin is sprayed upon the bleeding surface to arrest, bleeding by hastening blood clotting., SNAKE VENOM, Venom of some snakes (vipers, cobras and rattle, snakes) contains proteolytic enzymes which enhance, blood clotting by activating the clotting factors., EXTRACTS OF LUNGS AND THYMUS, Extract obtained from the lungs and thymus has, thromboplastin, which causes rapid blood coagulation., , OXIDIZED CELLULOSE, Oxidized cellulose causes clotting of blood by activating, the Hageman factor., , TESTS FOR BLOOD CLOTTING, Blood clotting tests are used to diagnose blood disorders., Some tests are also used to monitor the patients treated, with anticoagulant drugs such as heparin and warfarin., , Partial prothrombin time (PPT) is the time taken for the, blood to clot after adding an activator such as phospholipid, along with calcium to it. It is also called activated, partial prothrombin time (APTT). This test is useful in, monitoring the patients taking anticoagulant drugs., It is carried out by observing clotting time after, adding phospholipid, a surface activator and calcium, to a patient’s plasma. Phospholipid serves as platelet, substitute. Commonly used surface activator is kaolin.
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136 Section 2 t Blood and Body Fluids, Normal duration of partial prothrombin time is 30 to 45, seconds. It is prolonged in heparin or warfarin therapy, (since heparin and warfarin inhibit clotting) and deficiency, or inhibition of factors II, V, VIII, IX, X, XI and XII., INTERNATIONAL NORMALIZED RATIO, International normalized ratio (INR) is the rating of, a patient’s prothrombin time when compared to an, average. It measures extrinsic clotting pathway system., INR is useful in monitoring impact of anticoagulant, drugs such as warfarin and to adjust the dosage of, anticoagulants. Patients with atrial fibrillation are usually, treated with warfarin to protect against blood clot, which, may cause strokes. These patients should have regular, blood tests to know their INR in order to adjust warfarin, dosage., Blood takes longer time to clot if INR is higher., Normal INR is about 1. In patients taking anticoagulant, therapy for atrial fibrillation, INR should be between 2, and 3. For patients with heart valve disorders, INR, should be between 3 and 4. But, INR greater than 4, indicates that blood is clotting too slowly and there is a, risk of uncontrolled blood clotting., THROMBIN TIME, , Because of prolonged clotting time, even a mild, trauma causes excess bleeding which can lead to death., Damage of skin while falling or extraction of a tooth may, cause excess bleeding for few weeks. Easy bruising and, hemorrhage in muscles and joints are also common in, this disease., Causes of hemophilia, Hemophilia occurs due to lack of formation of prothrombin, activator. That is why the coagulation time is prolonged., The formation of prothrombin activator is affected due to, the deficiency of factor VIII, IX or XI., Types of hemophilia, Depending upon the deficiency of the factor involved,, hemophilia is classified into three types:, i. Hemophilia A or classic hemophilia: Due to, the deficiency of factor VIII. 85% of people with, hemophilia are affected by hemophilia A., ii. Hemophilia B or Christmas disease: Due to, the deficiency of factor IX. 15% of people with, hemophilia are affected by hemophilia B., iii. Hemophilia C or factor XI deficiency: Due to the, deficiency of factor XI. It is a very rare bleeding, disorder., , Thrombin time (TT) is the time taken for the blood to, clot after adding thrombin to it. It is done to investigate, the presence of heparin in plasma or to detect, fibrinogen abnormalities. This test involves observation, of clotting time after adding thrombin to patient’s, plasma. Normal duration of thrombin time is 12 to 20, seconds. It is prolonged in heparin therapy and during, dysfibrinogenimia (abnormal function of fibrinogen with, normal fibrinogen level)., , Symptoms of hemophilia, , APPLIED PHYSIOLOGY, , Treatment for hemophilia, , BLEEDING DISORDERS, , Effective therapy for classical hemophilia involves, replacement of missing clotting factor., , Bleeding disorders are the conditions characterized by, prolonged bleeding time or clotting time., Bleeding disorders are of three types:, 1. Hemophilia., 2. Purpura., 3. von Willebrand disease., 1. Hemophilia, Hemophilia is a group of sex-linked inherited blood, disorders, characterized by prolonged clotting time., However, the bleeding time is normal. Usually, it affects, the males, with the females being the carriers., , i. Spontaneous bleeding., ii. Prolonged bleeding due to cuts, tooth extraction, and surgery., iii. Hemorrhage in gastrointestinal and urinary, tracts., iv. Bleeding in joints followed by swelling and pain, v. Appearance of blood in urine., , 2. Purpura, Purpura is a disorder characterized by prolonged bleeding, time. However, the clotting time is normal. Characteristic, feature of this disease is spontaneous bleeding under, the skin from ruptured capillaries. It causes small tiny, hemorrhagic spots in many areas of the body. The, hemorrhagic spots under the skin are called purpuric, spots (purple colored patch like appearance). That is, why this disease is called purpura. Blood also sometimes, collects in large areas beneath the skin which are called, ecchymoses.
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Chapter 20 t Coagulation of Blood 137, Types and causes of purpura, , 2. Roughened endothelial lining, , Purpura is classified into three types depending upon, the causes:, , In infection, damage or arteriosclerosis, the endothelium, becomes rough and this initiates clotting., , i. Thrombocytopenic purpura, , 3. Sluggishness of blood flow, , Thrombocytopenic purpura is due to the deficiency of, platelets (thrombocytopenia). In bone marrow disease,, platelet production is affected leading to the deficiency, of platelets., , Decreased rate of blood flow causes aggregation of, platelets and formation of thrombus. Slowness of blood, flow occurs in reduced cardiac action, hypotension,, low metabolic rate, prolonged confinement to bed and, immobility of limbs., , ii. Idiopathic thrombocytopenic purpura, Purpura due to some unknown cause is called idiopathic, thrombocytopenic purpura. It is believed that platelet, count decreases due to the development of antibodies, against platelets, which occurs after blood transfusion., , 4. Agglutination of RBCs, Agglutination of the RBCs leads to thrombosis., Agglutination of RBCs occurs by the foreign antigens or, toxic substances., , iii. Thrombasthenic purpura, , 5. Toxic thrombosis, , Thrombasthenic purpura is due to structural or functional, abnormality of platelets. However, the platelet count is, normal. It is characterized by normal clotting time, normal, or prolonged bleeding time but defective clot retraction., , Thrombosis is common due to the action of chemical, poisons like arsenic compounds, mercury, poisonous, mushrooms and snake venom., , 3. von Willebrand Disease, , Protein C is a circulating anticoagulant, which inactivates, factors V and VIII. Thrombosis occurs in the absence, of this protein. Congenital absence of protein C causes, thrombosis and death in infancy., , von Willebrand disease is a bleeding disorder,, characterized by excess bleeding even with a mild injury., It is due to deficiency of von Willebrand factor, which is, a protein secreted by endothelium of damaged blood, vessels and platelets. This protein is responsible for, adherence of platelets to endothelium of blood vessels, during hemostasis after an injury. It is also responsible for, the survival and maintenance of factor VIII in plasma., Deficiency of von Willebrand factor suppresses, platelet adhesion. It also causes deficiency of factor, VIII. This results in excess bleeding, which resembles, the bleeding that occurs during platelet dysfunction or, hemophilia., THROMBOSIS, Thrombosis or intravascular blood clotting refers to, coagulation of blood inside the blood vessels. Normally,, blood does not clot in the blood vessel because of some, factors which are already explained. But some abnormal, conditions cause thrombosis., Causes of Thrombosis, 1. Injury to blood vessels, During infection or mechanical obstruction, the, endothelial lining of the blood vessel is damaged and it, initiates thrombosis., , 6. Congenital absence of protein C, , Complications of Thrombosis, 1. Thrombus, During thrombosis, lumen of blood vessels is occluded., The solid mass of platelets, red cells and/or clot, which, obstructs the blood vessel, is called thrombus. The, thrombus formed due to agglutination of RBC is called, agglutinative thrombus., 2. Embolism and embolus, Embolism is the process in which the thrombus or a, part of it is detached and carried in bloodstream and, occludes the small blood vessels, resulting in arrests of, blood flow to any organ or region of the body. Embolus, is the thrombus or part of it, which arrests the blood flow., The obstruction of blood flow by embolism is common in, lungs (pulmonary embolism), brain (cerebral embolism), or heart (coronary embolism)., 3. Ischemia, Insufficient blood supply to an organ or area of the body, by the obstruction of blood vessels is called ischemia., Ischemia results in tissue damage because of hypoxia, (lack of oxygen). Ischemia also causes discomfort,
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138 Section 2 t Blood and Body Fluids, pain and tissue death. Death of body tissue is called, necrosis., 4. Necrosis and infarction, Necrosis is a general term that refers to tissue death, caused by loss of blood supply, injury, infection,, inflammation, physical agents or chemical substances., , Infarction means the tissue death due to loss of, blood supply. Loss of blood supply is usually caused, by occlusion of an artery by thrombus or embolus and, sometimes by atherosclerosis (Chapter 67)., Area of tissue that undergoes infarction is called, infarct. Infarction commonly occurs in heart, brain, lungs,, kidneys and spleen.
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Chapter, , Blood Groups, , 21, , INTRODUCTION, ABO BLOOD GROUPS, , , , , , , , , , LANDSTEINER LAW, BLOOD GROUP SYSTEMS, ABO SYSTEM, DETERMINATION OF ABO GROUP, IMPORTANCE OF ABO GROUPS IN BLOOD TRANSFUSION, MATCHING AND CROSS-MATCHING, INHERITANCE OF ABO AGGLUTINOGENS AND AGGLUTININS, TRANSFUSION REACTIONS DUE TO ABO INCOMPATIBILITY, , Rh FACTOR, , , INHERITANCE OF Rh ANTIGEN, TRANSFUSION REACTIONS DUE TO Rh INCOMPATIBILITY, HEMOLYTIC DISEASE OF FETUS AND NEWBORN, , OTHER BLOOD GROUPS, , , , , LEWIS BLOOD GROUP, MNS BLOOD GROUPS, OTHER BLOOD GROUPS, , IMPORTANCE OF KNOWING BLOOD GROUP, , INTRODUCTION, When blood from two individuals is mixed, sometimes, clumping (agglutination) of RBCs occurs. This clumping, is because of the immunological reactions. But, why, clumping occurs in some cases and not in other cases, remained a mystery until the discovery of blood groups by, the Austrian Scientist Karl Landsteiner, in 1901. He was, honored with Nobel Prize in 1930 for this discovery., , ABO BLOOD GROUPS, Determination of ABO blood groups depends upon the, immunological reaction between antigen and antibody., Landsteiner found two antigens on the surface of RBCs, and named them as A antigen and B antigen. These, antigens are also called agglutinogens because of their, capacity to cause agglutination of RBCs. He noticed the, corresponding antibodies or agglutinins in the plasma, , and named them anti-A or α-antibody and anti-B or, β-antibody. However, a particular agglutinogen and the, corresponding agglutinin cannot be present together. If, present, it causes clumping of the blood. Based on this,, Karl Landsteiner classified the blood groups. Later it, became the ‘Landsteiner Law’ for grouping the blood., LANDSTEINER LAW, Landsteiner law states that:, 1. If a particular agglutinogen (antigen) is present in, the RBCs, corresponding agglutinin (antibody) must, be absent in the serum., 2. If a particular agglutinogen is absent in the RBCs,, the corresponding agglutinin must be present in the, serum., Though the second part of Landsteiner law is a fact, it is, not applicable to Rh factor.
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140 Section 2 t Blood and Body Fluids, BLOOD GROUP SYSTEMS, More than 20 genetically determined blood group, systems are known today. But, Landsteiner discovered, two blood group systems called the ABO system and, the Rh system. These two blood group systems are the, most important ones that are determined before blood, transfusions., , Based on the presence or absence of antigen A and, antigen B, blood is divided into four groups:, 1. ‘A’ group, 2. ‘B’ group, 3. ‘AB’ group, 4. ‘O’ group., Blood having antigen A belongs to ‘A’ group. This, blood has β-antibody in the serum. Blood with antigen B, and α-antibody belongs to ‘B’ group. If both the antigens, are present, blood group is called ‘AB’ group and serum, of this group does not contain any antibody. If both, antigens are absent, the blood group is called ‘O’ group, and both α and β antibodies are present in the serum., Antigens and antibodies present in different groups of, ABO system are given in Table 21.1. Percentage of, people among Asian and European population belonging, to different blood group is given in Table 21.2., ‘A’ group has two subgroups namely ‘A1’ and ‘A2’., Similarly ‘AB’ group has two subgroups namely ‘A1B’, and ‘A2B’., DETERMINATION OF ABO GROUP, Determination of the ABO group is also called blood, grouping, blood typing or blood matching., Principle of Blood Typing – Agglutination, Blood typing is done on the basis of agglutination., Agglutination means the collection of separate particles, like RBCs into clumps or masses. Agglutination occurs, if an antigen is mixed with its corresponding antibody, which is called isoagglutinin. Agglutination occurs when, TABLE 21.1: Antigen and antibody present in, ABO blood groups, Antigen in RBC, , A, , B, , AB, , O, , Indians, , Population, , 23, , 33, , 7, , 37, , Asians, , 25, , 25, , 5, , 45, , Europeans, , 42, , 9, , 3, , 46, , A antigen is mixed with anti-A or when B antigen is mixed, with anti-B., , ABO SYSTEM, , Group, , TABLE 21.2: Percentage of people having, different blood groups, , Antibody in serum, , A, , A, , Anti-B ( β ), , B, , B, , Anti-A ( α ), , AB, , A and B, , No antibody, , O, , No antigen, , Anti-A and Anti-B, , Requisites for Blood Typing, To determine the blood group of a person, a suspension, of his RBC and testing antisera are required. Suspension, of RBC is prepared by mixing blood drops with isotonic, saline (0.9%)., Test sera are:, 1. Antiserum A, containing anti-A or α-antibody., 2. Antiserum B, containing anti-B or β-antibody., Procedure, 1. One drop of antiserum A is placed on one end of a, glass slide (or a tile) and one drop of antiserum B on, the other end., 2. One drop of RBC suspension is mixed with each, antiserum. The slide is slightly rocked for 2 minutes., The presence or absence of agglutination is observed, by naked eyes and if necessary, it is confirmed by, using microscope., 3. Presence of agglutination is confirmed by the, presence of thick masses (clumping) of RBCs, 4. Absence of agglutination is confirmed by clear, mixture with dispersed RBCs., Results, 1. If agglutination occurs with antiserum A: The antiserum A contains α-antibody. The agglutination, occurs if the RBC contains A antigen. So, the blood, group is A (Fig. 21.1)., 2. If agglutination occurs with antiserum B: The antiserum B contains β-antibody. The agglutination, occurs if the RBC contains B antigen. So, the blood, group is B., 3. If agglutination occurs with both antisera A and B:, The RBC contains both A and B antigens to cause, agglutination. And, the blood group is AB., 4. If agglutination does not occur either with antiserum, A or antiserum B: The agglutination does not occur, because RBC does not contain any antigen. The, blood group is O.
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Chapter 21 t Blood Groups 141, person needs blood transfusion, another test called, cross-matching is done after the blood is typed. It is, done to find out whether the person’s body will accept, the donor’s blood or not., For blood matching, RBC of the individual (recipient), and test sera are used. Cross-matching is done by, mixing the serum of the recipient and the RBCs of donor., Cross-matching is always done before blood transfusion., If agglutination of RBCs from a donor occurs during, cross-matching, the blood from that person is not used, for transfusion., Matching, = Recipient’s RBC + Test sera., Cross-matching = Recipient’s serum + Donor’s RBC., INHERITANCE OF ABO AGGLUTINOGENS, AND AGGLUTININS, , FIGURE 21.1: Determination of blood group, , IMPORTANCE OF ABO GROUPS, IN BLOOD TRANSFUSION, During blood transfusion, only compatible blood must be, used. The one who gives blood is called the ‘donor’ and, the one who receives the blood is called ‘recipient’., While transfusing the blood, antigen of the donor, and the antibody of the recipient are considered. The, antibody of the donor and antigen of the recipient are, ignored mostly., Thus, RBC of ‘O’ group has no antigen and so, agglutination does not occur with any other group of, blood. So, ‘O’ group blood can be given to any blood, group persons and the people with this blood group are, called ‘universal donors’., Plasma of AB group blood has no antibody. This does, not cause agglutination of RBC from any other group of, blood. People with AB group can receive blood from any, blood group persons. So, people with this blood group, are called ‘universal recipients’., MATCHING AND CROSS-MATCHING, Blood matching (typing) is a laboratory test done to, determine the blood group of a person. When the, , Blood group of a person depends upon the two genes, inherited from each parent. Gene A and gene B are, dominant by themselves and gene O is recessive., Inheritance of blood group is represented schematically, as given in Table 21.3., Agglutinogens appear during the 6th month of, fetal life. Concentration at birth is 1/5 of the adult, concentration. It rises to the adult level at puberty., Agglutinogens are present not only in RBCs but also, present in many organs like salivary glands, pancreas,, kidney, liver, lungs, etc. The A and B agglutinogens are, inherited from the parents as Mendelian phenotypes., Agglutinin α or β is not produced during fetal life. It, starts appearing only 2 or 3 months after birth. Agglutinin, is produced in response to A or B agglutinogens which, enter the body through respiratory system or digestive, system along with bacteria., Agglutinins are the gamma-globulins which are, mainly IgG and IgM immunoglobulins., TRANSFUSION REACTIONS, DUE TO ABO INCOMPATIBILITY, Transfusion reactions are the adverse reactions in the, body, which occur due to transfusion error that involves, transfusion of incompatible (mismatched) blood. The, reactions may be mild causing only fever and hives (skin, disorder characterized by itching) or may be severe, leading to renal failure, shock and death., In mismatched transfusion, the transfusion reactions, occur between donor’s RBC and recipient’s plasma., So, if the donor’s plasma contains agglutinins against, recipient’s RBC, agglutination does not occur because, these antibodies are diluted in the recipient’s blood., But, if recipient’s plasma contains agglutinins against, donor’s RBCs, the immune system launches a response
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142 Section 2 t Blood and Body Fluids, TABLE 21.3: Inheritance of ABO group, Group of, offspring, , Gene from parents, , serum bilirubin level increases above 2 mg/dL, jaundice, occurs (Chapter 40)., , Genotype, , 2. Cardiac Shock, , A+A, A+O, , A, , AA or AO, , B+B, B+O, , B, , BB or BO, , A+B, O+O, , AB, O, , AB, OO, , against the new blood cells. Donor RBCs are agglutinated resulting in transfusion reactions., Severity of Transfusion Reactions, Severity of transfusion reactions varies from mild (fever, and chills) to severe (acute kidney failure, shock and, death). Severity depends upon the amount of blood transfused, type of reaction and general health of the patient., Cause for Transfusion Reactions, Transfusion of incompatible blood produces hemolytic, reactions. The recipient’s antibodies (IgG or IgM), adhere to the donor RBCs, which are agglutinated and, destroyed. Large amount of free hemoglobin is liberated, into plasma. This leads to transfusion reactions., Signs and Symptoms of Transfusion Reactions, Non-hemolytic transfusion reaction, Non-hemolytic transfusion reaction develops within a, few minutes to hours after the commencement of blood, transfusion. Common symptoms are fever, difficulty in, breathing and itching., Hemolytic transfusion reaction, Hemolytic transfusion reaction may be acute or delayed., The acute hemolytic reaction occurs within few minutes, of transfusion. It develops because of rapid hemolysis of, donor’s RBCs. Symptoms include fever, chills, increased, heart rate, low blood pressure, shortness of breath,, bronchospasm, nausea, vomiting, red urine, chest, pain, back pain and rigor. Some patients may develop, pulmonary edema and congestive cardiac failure., Delayed hemolytic reaction occurs from 1 to 5 days, after transfusion. The hemolysis of RBCs results in, release of large amount of hemoglobin into the plasma., This leads to the following complications., 1. Jaundice, Normally, hemoglobin released from destroyed RBC, is degraded and bilirubin is formed from it. When the, , Simultaneously, hemoglobin released into the plasma, increases the viscosity of blood. This increases the, workload on the heart leading to heart failure. Moreover,, toxic substances released from hemolyzed cells reduce, the arterial blood pressure and develop circulatory shock, (Fig. 21.2)., 3. Renal Shutdown, Dysfunction of kidneys is called renal shutdown., The toxic substances from hemolyzed cells cause, constriction of blood vessels in kidney. In addition,, the toxic substances along with free hemoglobin are, filtered through glomerular membrane and enter renal, tubules. Because of poor rate of reabsorption from renal, tubules, all these substances precipitate and obstruct, the renal tubule. This suddenly stops the formation of, urine (anuria)., If not treated with artificial kidney, the person dies, within 10 to 12 days because of jaundice, circulatory, shock and more specifically due to renal shutdown and, anuria., , Rh FACTOR, Rh factor is an antigen present in RBC. This antigen, was discovered by Landsteiner and Wiener. It was first, discovered in Rhesus monkey and hence the name, ‘Rh factor’. There are many Rh antigens but only the D, antigen is more antigenic in human., The persons having D antigen are called ‘Rh positive’, and those without D antigen are called ‘Rh negative’., Among Indian population, 85% of people are Rh positive, and 15% are Rh negative. Percentage of Rh positive, people is more among black people., Rh group system is different from ABO group system, because, the antigen D does not have corresponding, natural antibody (anti-D). However, if Rh positive blood is, transfused to a Rh negative person anti-D is developed, in that person. On the other hand, there is no risk of, complications if the Rh positive person receives Rh, negative blood., INHERITANCE OF Rh ANTIGEN, Rhesus factor is an inherited dominant factor. It may be, homozygous Rhesus positive with DD or heterozygous, Rhesus positive with Dd (Fig. 21.3). Rhesus negative, occurs only with complete absence of D (i.e. with, homozygous dd).
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Chapter 21 t Blood Groups 143, postpartum period, i.e. within a month after delivery, the, mother develops Rh antibody in her blood., When the mother conceives for the second time, and if the fetus happens to be Rh positive again, the Rh, antibody from mother’s blood crosses placental barrier, and enters the fetal blood. Thus, the Rh antigen cannot, cross the placental barrier, whereas Rh antibody can, cross it., , FIGURE 21.2: Complications of mismatched blood transfusion, , TRANSFUSION REACTIONS DUE, TO Rh INCOMPATIBILITY, When a Rh negative person receives Rh positive, blood for the first time, he is not affected much, since, the reactions do not occur immediately. But, the Rh, antibodies develop within one month. The transfused, RBCs, which are still present in the recipient’s blood,, are agglutinated. These agglutinated cells are lysed by, macrophages. So, a delayed transfusion reaction occurs., But, it is usually mild and does not affect the recipient., However, antibodies developed in the recipient remain, in the body forever. So, when this person receives Rh, positive blood for the second time, the donor RBCs are, agglutinated and severe transfusion reactions occur, immediately (Fig. 21.4). These reactions are similar to, the reactions of ABO incompatibility (see above)., HEMOLYTIC DISEASE OF FETUS AND, NEWBORN – ERYTHROBLASTOSIS FETALIS, Hemolytic disease is the disease in fetus and newborn,, characterized by abnormal hemolysis of RBCs. It is due, to Rh incompatibility, i.e. the difference between the Rh, blood group of the mother and baby. Hemolytic disease, leads to erythroblastosis fetalis., Erythroblastosis fetalis is a disorder in fetus,, characterized by the presence of erythroblasts in, blood. When a mother is Rh negative and fetus is Rh, positive (the Rh factor being inherited from the father),, usually the first child escapes the complications of Rh, incompatibility. This is because the Rh antigen cannot, pass from fetal blood into the mother’s blood through the, placental barrier., , However, at the time of parturition (delivery of the, child), the Rh antigen from fetal blood may leak into, mother’s blood because of placental detachment. During, , FIGURE 21.3: Inheritance of Rh antigen
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144 Section 2 t Blood and Body Fluids, Rh antibody which enters the fetus causes, agglutination of fetal RBCs resulting in hemolysis., Severe hemolysis in the fetus causes jaundice. To, compensate the hemolysis of more and more number of, RBCs, there is rapid production of RBCs, not only from, bone marrow, but also from spleen and liver. Now, many, large and immature cells in proerythroblastic stage are, released into circulation. Because of this, the disease is, called erythroblastosis fetalis., Ultimately due to excessive hemolysis severe complications develop, viz., 1. Severe anemia, 2. Hydrops fetalis, 3. Kernicterus., 1. Severe Anemia, Excessive hemolysis results in anemia and the infant, dies when anemia becomes severe., 2. Hydrops Fetalis, Hydrops fetails is a serious condition in fetus, characterized by edema. Severe hemolysis results in the, development of edema, enlargement of liver and spleen, and cardiac failure. When this condition becomes more, severe, it may lead to intrauterine death of fetus., 3. Kernicterus, Kernicterus is the form of brain damage in infants, caused by severe jaundice. If the baby survives anemia, in erythroblastosis fetalis (see above), then kernicterus, develops because of high bilirubin content., The blood-brain barrier is not well developed in, infants as in the adults (Chapter 163). So, the bilirubin, enters the brain and causes permanent brain damage., Most commonly affected parts of brain are basal ganglia,, hippocampus, geniculate bodies, cerebellum and cranial, nerve nuclei. The features of this disease are:, i. When brain damage starts, the babies become, lethargic and sleepy. They have high-pitched, cry, hypotonia and arching of head backwards., ii. As the disease progresses, they develop, hypertonia and opisthotonus (Chapter 155)., iii. Advanced signs of the disease are inability, to suckle milk, irritability and crying, bicycling, movements, choreoathetosis (Chapter 151),, spasticity, (Chapter 34) seizures (Chapter 161),, fever and coma., , should be administered to the mother at 28th, and 34th weeks of gestation, as prophylactic, measure. If Rh negative mother delivers Rh, positive baby, then anti D should be administered, to the mother within 48 hours of delivery. This, develops passive immunity and prevents the, formation of Rh antibodies in mother’s blood., So, the hemolytic disease of newborn does not, occur in a subsequent pregnancy., ii. If the baby is born with erythroblastosis fetalis,, the treatment is given by means of exchange, transfusion (Chapter 22). Rh negative blood, is transfused into the infant, replacing infant’s, own Rh positive blood. It will now take at least, 6 months for the infant’s new Rh positive blood, to replace the transfused Rh negative blood., By this time, all the molecules of Rh antibody, derived from the mother get destroyed., , OTHER BLOOD GROUPS, In addition to ABO blood groups and Rh factor, many, more blood group systems were found, such as Lewis, blood group and MNS blood groups. However, these, systems of blood groups do not have much clinical, importance., LEWIS BLOOD GROUP, Lewis blood group was first found in a subject named, Mrs Lewis. The antibody that was found in this lady, reacted with the antigens found on RBCs and in body, , Prevention or treatment for erythroblastosis fetalis, i. If mother is found to be Rh negative and fetus is, Rh positive, anti D (antibody against D antigen), , FIGURE 21.4: Rh incompatibility
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Chapter 21 t Blood Groups 145, fluids such as saliva, gastric juice, etc. The antigens,, which are named Lewis antigens are formed in the tissues,, released in the body secretions and then absorbed by the, RBC membrane. Because of secretion along with body, secretions, these antigens are also known as secretor, antigens. Presence of Lewis antigens in children leads to, some complications such as retarded growth. Sometimes,, it causes transfusion reactions also., MNS BLOOD GROUPS, MNS blood groups are determined by their reactions, with anti-M, anti-N and anti-S. However, these blood, groups rarely cause any trouble like hemolysis following, transfusion., OTHER BLOOD GROUPS, Other blood groups include:, i. Auberger groups, ii. Diego group, iii. Bombay group, iv. Duffy group, v. Lutheran group, , vi., vii., viii., ix., x., , P group, Kell group, I group, Kidd group, Sulter Xg group., , IMPORTANCE OF KNOWING, BLOOD GROUP, Nowadays, knowledge of blood group is very essential, medically, socially and judicially. The importance of, knowing blood group is:, 1. Medically, it is important during blood transfusions, and in tissue transplants., 2. Socially, one should know his or her own blood, group and become a member of the Blood Donor’s, Club so that he or she can be approached for blood, donation during emergency conditions., 3. It general among the couples, knowledge of blood, groups helps to prevent the complications due to Rh, incompatibility and save the child from the disorders, like erythroblastosis fetalis., 4. Judicially, it is helpful in medico-legal cases to sort, out parental disputes.
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Chapter, , Blood Transfusion, , , , , , , , 22, , INTRODUCTION, PRECAUTIONS, HAZARDS OF BLOOD TRANSFUSION, BLOOD SUBSTITUTES, EXCHANGE TRANSFUSION, AUTOLOGOUS BLOOD TRANSFUSION, , INTRODUCTION, Blood transfusion is the process of transferring blood, or blood components from one person (the donor), into the bloodstream of another person (the recipient)., Transfusion is done as a life-saving procedure to replace, blood cells or blood products lost through bleeding., CONDITIONS WHEN BLOOD TRANSFUSION, IS NECESSARY, Blood transfusion is essential in the following conditions:, 1. Anemia, 2. Hemorrhage, 3. Trauma, 4. Burns, 5. Surgery., , PRECAUTIONS, Certain precautions must be followed before and during, the transfusion of blood to a patient., PRECAUTIONS TO BE TAKEN BEFORE, THE TRANSFUSION OF BLOOD, 1. Donor must be healthy, without any diseases like:, a. Sexually transmitted diseases such as syphilis, b. Diseases caused by virus like hepatitis, AIDS,, etc., , 2. Only compatible blood must be transfused, 3. Both matching and cross-matching must be done, 4. Rh compatibility must be confirmed., PRECAUTIONS TO BE TAKEN WHILE, TRANSFUSING BLOOD, 1. Apparatus for transfusion must be sterile, 2. Temperature of blood to be transfused must be, same as the body temperature, 3. Transfusion of blood must be slow. The sudden, rapid infusion of blood into the body increases the, load on the heart, resulting in many complications., , HAZARDS OF BLOOD TRANSFUSION, Hazards of blood transfusion are of four types:, 1. Reactions due to mismatched (incompatible) blood, transfusion – transfusion reactions, 2. Reactions due to massive blood transfusion, 3. Reactions due to faulty techniques during blood, transfusion, 4. Transmission of infections., REACTIONS DUE TO MISMATCHED BLOOD, TRANSFUSION – TRANSFUSION REACTIONS, Transfusion reactions due to ABO incompatibility and Rh, incompatibility are explained in the Chapter 21.
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Chapter 22 t Blood Transfusion 147, REACTIONS DUE TO MASSIVE, BLOOD TRANSFUSION, Massive transfusion is the transfusion of blood equivalent, or more than the patient’s own blood volume. It leads to, i. Circulatory shock, particularly in patients suffering from chronic anemia, cardiac diseases or, renal diseases, ii. Hyperkalemia due to increased potassium, concentration in stored blood, iii. Hypocalcemia leading to tetany due to massive, transfusion of citrated blood, iv. Hemosiderosis (increased deposition of ion, in the form of hemosiderin, in organs such as, endocrine glands, heart and liver) due to iron, overload after repeated transfusions., REACTIONS DUE TO FAULTY TECHNIQUES, DURING BLOOD TRANSFUSION, Faulty techniques adapted during blood transfusion, leads to:, i. Thrombophlebitis (inflammation of vein,, associated with formation of thrombus)., ii. Air embolism (obstruction of blood vessel due to, entrance of air into the bloodstream)., TRANSMISSION OF INFECTIONS, Blood transfusion without precaution leads to transmission of blood-borne infections such as:, i. HIV, ii. Hepatitis B and A, iii. Glandular fever or infectious mononucleosis, (acute infectious disease caused by EpsteinBarr virus and characterized by fever, swollen, lymph nodes, sore throat and abnormal, lymphocytes), iv. Herpes (viral disease with eruption of small, blister-like vesicles on skin or membranes), v. Bacterial infections., , BLOOD SUBSTITUTES, Fluids infused into the body instead of whole blood are, known as blood substitutes., Commonly used blood substitutes are:, 1. Human plasma, 2. 0.9% sodium chloride solution (saline) and 5%, glucose, 3. Colloids like gum acacia, isinglass, albumin and, animal gelatin., , EXCHANGE TRANSFUSION, Exchange transfusion is the procedure which involves, removal of patient’s blood completely and replacement, with fresh blood or plasma of the donor. It is otherwise, known as replacement transfusion. It is an important, life-saving procedure carried out in conditions such as, severe jaundice, sickle cell anemia, erythroblastosis, fetalis, etc., PROCEDURE, Procedure involves both removal and replacement of, affected blood in stages. Exchange transfusion is carried, out in short cycles of few minutes duration, as follows:, 1. Affected person’s blood is slowly drawn out in small, quantities of 5 to 20 mL, depending upon the age and, size of the person and the severity of the condition., 2. Equal quantity of fresh, prewarmed blood or plasma, is infused through intravenous catheter. This is, carried out for few minutes., 3. Catheter is left in place and the transfusion is, repeated within few hours., 4. This procedure is continued till the whole or, predetermined volume of blood is exchanged., CONDITIONS WHICH NEED, EXCHANGE TRANSFUSION, 1. Hemolytic disease of the newborn (erythroblastosis, fetalis)., 2. Severe sickle cell anemia., 3. Severe polycythemia (replacement with saline,, plasma or albumin)., 4. Toxicity of certain drugs., 5. Severe jaundice in newborn babies, which does, not respond to ultraviolet light therapy. Normally,, neonatal jaundice is treated by exposure to ultraviolet, rays. It breaks down the bilirubin which is excreted, by liver., , AUTOLOGOUS BLOOD TRANSFUSION, Autologous blood transfusion is the collection and, reinfusion of patient’s own blood. It is also called self, blood donation. The conventional transfusion of blood, that is collected from persons other than the patient is, called allogeneic or heterologous blood transfusion., Autologous blood transfusion is used for planned, surgical procedures. Patient’s blood is withdrawn in, advance and stored. Later, it is infused if necessary, during surgery., This type of blood transfusion prevents the transmission of viruses such as HIV or hepatitis B. It also, eliminates transfusion reactions.
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Chapter, , Blood Volume, , , , , , , 23, , NORMAL BLOOD VOLUME, VARIATIONS, MEASUREMENT, REGULATION, APPLIED PHYSIOLOGY, , NORMAL BLOOD VOLUME, Total amount of blood present in the circulatory system,, blood reservoirs, organs and tissues together constitute, blood volume. In a normal young healthy adult male, weighing about 70 kg, the blood volume is about 5 L. It, is about 7% of total body weight. It ranges between 6%, and 8% of body weight. In relation to body surface area,, blood volume is 2.8 to 3.1 L/sq M., , activity, body weight and surface area of the body. In, females, it is slightly less because of loss of blood through, menstruation, more fats and less body surface area., 3. Surface Area of the Body, Blood volume is directly proportional to the surface area, of the body., 4. Body Weight, , VARIATIONS IN BLOOD VOLUME, , Blood volume is directly proportional to body weight., , PHYSIOLOGICAL VARIATIONS, , 5. Atmospheric Temperature, , 1. Age, , Exposure to cold environment reduces the blood volume, and exposure to warm environment increases the blood, volume., , Absolute blood volume is less at birth and it increases, steadily as the age advances. However, at birth, the, blood volume is more when compared to body weight, and less when compared to the body surface area. At, birth and at 24 hours after birth, the blood volume is, about 80 mL/kg body weight. At the end of 6 months, it, increases to about 86 mL/kg. At the end of one year, it, is about 80 mL/kg. It remains at this level until 6 years of, age. At 10 years, it is about 75 mL/kg. At the age of 15, years, the blood volume is about 70 mL/kg body weight,, which is almost the adult volume., , 6. Pregnancy, During early stage of pregnancy, blood volume increases, by 20% to 30% due to the increased fetal mass and, sodium retention. However, it reduces in later stages., 7. Exercise, Exercise increases the blood volume by increasing the, release of erythropoietin and production of more RBCs., , 2. Sex, , 8. Posture, , In males, the blood volume is slightly more than in, females because of the increase in erythropoietic, , Standing (erect posture) for long time reduces the blood, volume by about 15%. It is because the pooling of blood
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Chapter 23 t Blood Volume 149, in lower limbs while standing increases the hydrostatic, pressure. This pressure pushes fluid from blood vessels, into the tissue spaces; so blood volume decreases., 9. High Altitude, Blood volume increases in high altitude. It is because of, hypoxia, which stimulates the secretion of erythropoietin., It induces the production of more RBCs, which leads to, increase in blood volume., 10. Emotion, Excitement increases blood volume. It is because of, sympathetic stimulation, which causes splenic contrac, tion and release of stored blood into circulation., PATHOLOGICAL VARIATIONS, Abnormal increase in blood volume is called hypervolemia, and abnormal decrease in blood volume is called, hypovolemia. Refer applied physiology for details., , MEASUREMENT OF BLOOD VOLUME, Blood volume is measured by two methods, direct, method and indirect method., DIRECT METHOD, , Determination of Plasma Volume, Plasma volume is determined by two methods:, i. Indicator or dye dilution technique, ii. Radioisotope method., i. Determination of plasma volume by indicator or dye, dilution technique, Principles and other details of this technique are explained, in Chapter 6. The dye which is used to measure plasma, volume is Evans blue or T1824., Procedure, 10 mL of blood is drawn from the subject. This is divided, into 2 equal portions. To one part, a known quantity of, the dye is added. This is used as control sample in the, procedure. The other portion is used to determine the, hematocrit value., Then, a known volume of the dye is injected intra, venously. After 10 minutes, a sample of blood is drawn., Then, another 4 samples of blood are collected at the, interval of 10 minutes. All the 5 samples are centrifuged, and plasma is separated from the samples. In each, sample of plasma, the concentration of the dye is, measured by colorimetric method and the average, concentration is found., The subject’s urine is collected and the amount of, dye excreted in the urine is measured., , Direct method is employed only in animals because, it involves sacrificing the life. The animal is killed by, decapitation and the blood is collected. The blood, vessels and the tissues are washed thoroughly with, known quantity of water or saline. And, this is added, to the blood collected already. The total volume is, measured. From this, the volume of water or saline used, for washing the tissues is deducted to obtain the volume, of the blood in the animal., This method was first employed by Welcker, in, 1854. Later, B’Schoff employed the same method on, decapitated criminals, to determine the blood volume in, human beings., , Calculation, , INDIRECT METHOD, , Determination of Blood Cell Volume, , Indirect method is advantageous because, it is used, to measure the blood volume in human beings without, causing any discomfort or any difficulty to the subject., Measurement of total blood volume involves two, steps:, 1. Determination of plasma volume, 2. Determination of blood cell volume., , Blood cell volume is determined by two methods:, i. By hematocrit value, ii. By radioisotope method., , Plasma volume is determined by using the formula,, Volume =, , Amount of dye injected – Amount excreted, Average concentration of dye in plasma, , ii. Determination of plasma volume by radioisotope, method, Radioactive iodine (131I or 132I) is injected. After sometime,, a sample of blood is collected. The radioactivity is, determined by using appropriate counter. From this, the, plasma volume is determined., , i. Determination of blood cell volume by hematocrit value, This is usually done by centrifuging the blood and, measuring the packed cell volume (Chapter 13). Packed
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150 Section 2 t Blood and Body Fluids, cell volume (PCV) is expressed in percentage. If this is, deducted from 100, the percentage of plasma is known., From this and from the volume of plasma, the amount of, total blood is calculated by using the formula., Blood volume =, , 2. Hyperaldosteronism, In hyperaldosteronism, excess retention of sodium and, water leads to increase in the ECF volume and blood, volume., , 100 × Amount of plasma, 100 – PCV, , ii. Determination of blood cell volume by radioisotope, method, , 3. Cirrhosis of the Liver, In this condition, the blood volume is more because of, increase in the plasma volume., , Volume of blood cell is measured by radioisotope, method also. Radioactive chromium (Cr52) is added, with heparinized blood and incubated for 2 hours at, 37°C. During this time, all the red cells in the blood are, ‘tagged’ with Cr52. Then, this is injected intravenously., After giving sufficient time for mixing, a sample of blood, is drawn. Hematocrit value is determined by measuring, the radioactivity in the blood sample. Radioactive iron, (Fe59, Fe55) or radioactive phosphorus (P32) is also used, for determining the hematocrit value., , 4. Congestive Cardiac Failure, , REGULATION OF BLOOD VOLUME, , 1. Hemorrhage or Blood Loss, , Various mechanisms are involved in the regulation of, blood volume. The important ones are the renal and, hormonal mechanisms. Hypothalamus plays a vital role, in the activation of these two mechanisms during the, regulation of blood volume., When blood volume increases, hypothalamus, causes loss of fluid from the body. When the blood, volume reduces, hypothalamus induces retention of, water. Hypothalamus regulates the extracellular fluid, (ECF) volume and blood volume by acting mainly through, kidneys and sweat glands and by inducing thirst. This, function of hypothalamus is described in Chapter 149., Hormones also are involved in the regulation of, blood volume through the regulation of ECF volume., Hormones which are involved in the maintenance of, ECF volume are:, 1. Antidiuretic hormone (Chapter 66), 2. Aldosterone (Chapter 70), 3. Cortisol (Chapter 70), 4. Atrial natriuretic peptide (Chapter 72)., , Acute hemorrhage occurs due to cuts or accidents., The chronic hemorrhage occurs in ulcers, bleeding, piles and excessive uterine bleeding in females during, menstruation., , APPLIED PHYSIOLOGY, HYPERVOLEMIA, Increase in blood volume is called hypervolemia. It, occurs in the following pathological conditions:, , Retention of sodium occurs in this condition. Sodium, retention leads to water retention and increase in ECF, volume, plasma volume and blood volume., HYPOVOLEMIA, Decrease in blood volume is called hypovolemia. It, occurs in the following pathological conditions:, , 2. Fluid Loss, Fluid loss occurs in burns, vomiting, diarrhea, excessive, sweating and polyuria., 3. Hemolysis, Excessive destruction of RBCs occurs because of the, presence of various hemolytic agents and other factors, such as, hypotonic solution, snake venom, acidity or, alkalinity, mismatched blood transfusion, hemorrhagic, smallpox and measles., 4. Anemia, Blood volume decreases in various types of anemia, because of decrease in RBC count. In some cases,, the quantity (volume) of blood remains the same but, the quality of the blood alters. Blood becomes dilute, (hemodilution) because of the entrance of fluid into the, blood vessel., 5. Hypothyroidism, , 1. Hyperthyroidism, Blood volume increases because thyroxine increases, the RBC count and plasma volume., , During hypothyroidism, the blood volume is decreased, because of reduction in plasma volume and RBC, count.
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Reticuloendothelial System Chapter, and Tissue Macrophage, , 24, , DEFINITION AND DISTRIBUTION, , , , RETICULOENDOTHELIAL SYSTEM OR MACROPHAGE SYSTEM, MACROPHAGE, , CLASSIFICATION OF RETICULOENDOTHELIAL CELLS, , , , FIXED RETICULOENDOTHELIAL CELLS – TISSUE MACROPHAGES, WANDERING RETICULOENDOTHELIAL CELLS AND TISSUE MACROPHAGES, , FUNCTIONS OF RETICULOENDOTHELIAL SYSTEM, , DEFINITION AND DISTRIBUTION, RETICULOENDOTHELIAL SYSTEM OR, MACROPHAGE SYSTEM, Reticuloendothelial system or tissue macrophage system is, the system of primitive phagocytic cells, which play an important role in defense mechanism of the body. The reticuloendothelial cells are found in the following structures:, 1. Endothelial lining of vascular and lymph channels., 2. Connective tissue and some organs like spleen,, liver, lungs, lymph nodes, bone marrow, etc., Reticular cells in these tissues form the tissue, macrophage system., MACROPHAGE, Macrophage is a large phagocytic cell, derived from, monocyte (Chapter 17)., , CLASSIFICATION OF, RETICULOENDOTHELIAL CELLS, , Tissue macrophages are present in the following, areas:, 1. Connective Tissue, Reticuloendothelial cells in connective tissues and in, serous membranes like pleura, omentum and mesentery, are called the fixed macrophages of connective tissue., 2. Endothelium of Blood Sinusoid, Endothelium of the blood sinusoid in bone marrow,, liver, spleen, lymph nodes, adrenal glands and pituitary, glands also contain fixed cells. Kupffer cells present in, liver belong to this category., 3. Reticulum, Reticulum of spleen, lymph node and bone marrow, contain fixed reticuloendothelial cells., 4. Central Nervous System, , Reticuloendothelial cells are classified into two types:, 1. Fixed reticuloendothelial cells or tissue macrophages., 2. Wandering reticuloendothelial cells., , Meningocytes of meninges and microglia form the tissue, macrophages of brain., , FIXED RETICULOENDOTHELIAL CELLS –, TISSUE MACROPHAGES, , Tissue macrophages are present in the alveoli of lungs., , Fixed reticuloendothelial cells are also called the tissue, macrophages or fixed histiocytes because, these cells, are usually located in the tissues., , 5. Lungs, , 6. Subcutaneous Tissue, Fixed reticuloendothelial, subcutaneous tissue also., , cells, , are, , present, , in
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152 Section 2 t Blood and Body Fluids, WANDERING RETICULOENDOTHELIAL, CELLS AND TISSUE MACROPHAGES, Wandering reticuloendothelial cells are also called, free histiocytes. There are two types of wandering, reticuloendothelial cells:, 1. Free Histiocytes of Blood, i. Neutrophils, ii. Monocytes, which become macrophages and, migrate to the site of injury or infection., , 3. Secretion of Interleukins, Tissue macrophages secrete the following interleukins,, which help in immunity:, i. Interleukin-1 (IL-1): Accelerates the maturation, and proliferation of specific B lymphocytes and, T lymphocytes., ii. Interleukin-6 (IL-6): Causes the growth of B, lymphocytes and production of antibodies., iii. Interleukin-12 (IL-12): Influences the T helper, cells., , 2. Free Histiocytes of Solid Tissue, , 4. Secretion of Tumor Necrosis Factors, , During emergency, the fixed histiocytes from connective, tissue and other organs become wandering cells and, enter the circulation., , Two types of tumor necrosis factors (TNF) are secreted, by tissue macrophages:, i. TNF-α: Causes necrosis of tumor and activates, the immune responses in the body, ii. TNF-β: Stimulates immune system and vascular, response, in addition to causing necrosis of, tumor., , FUNCTIONS OF, RETICULOENDOTHELIAL SYSTEM, Reticuloendothelial system plays an important role in the, defense mechanism of the body. Most of the functions, of the reticuloendothelial system are carried out by the, tissue macrophages., Functions of tissue macrophages:, 1. Phagocytic Function, Macrophages are the large phagocytic cells, which, play an important role in defense of the body by, phagocytosis., When any foreign body invades, macrophages, ingest them by phagocytosis and liberate the antigenic, products of the organism. The antigens activate the, helper T lymphocytes and B lymphocytes. (Refer, Chapter 17 for details)., Lysosomes of macrophages contain proteolytic, enzymes and lipases, which digest the bacteria and, other foreign bodies., , 5. Secretion of Transforming Growth Factor, Tissue macrophages secrete transforming growth factor,, which plays an important role in preventing rejection of, transplanted tissues or organs by immunosuppression., 6. Secretion of Colony-stimulation Factor, Colony-stimulation factor (CSF) secreted by macrophages is M-CSF. It accelerates the growth of granulocytes, monocytes and macrophages., 7. Secretion of Platelet-derived Growth Factor, Tissue macrophages secrete the platelet-derived growth, factor (PDGF), which accelerates repair of damaged, blood vessel and wound healing., 8. Removal of Carbon Particles and Silicon, , 2. Secretion of Bactericidal Agents, Tissue macrophages secrete many bactericidal agents, which kill the bacteria. The important bactericidal agents, of macrophages are the oxidants. An oxidant is a, substance that oxidizes another substance., Oxidants secreted by macrophages are:, i. Superoxide (O2– ), ii. Hydrogen peroxide (H2O2), iii. Hydroxyl ions (OH–)., These oxidants are the most potent bactericidal, agents. So, even the bacteria which cannot be digested, by lysosomal enzymes are degraded by these oxidants., , Macrophages ingest the substances like carbon dust, particles and silicon, which enter the body., 9. Destruction of Senile RBC, Reticuloendothelial cells, particularly those in spleen, destroy the senile RBCs and release hemoglobin, (Chapter 9)., 10. Destruction of Hemoglobin, Hemoglobin released from broken senile RBCs is degraded by the reticuloendothelial cells (Chapter 11).
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Chapter, , Spleen, , 25, , STRUCTURE, , , , RED PULP, WHITE PULP, , FUNCTIONS, , , , , , FORMATION OF BLOOD CELLS, DESTRUCTION OF BLOOD CELLS, BLOOD RESERVOIR FUNCTION, ROLE IN DEFENSE OF BODY, , APPLIED PHYSIOLOGY, , , , SPLENOMEGALY AND HYPERSPLENISM, HYPOSPLENISM AND ASPLENIA, , STRUCTURE OF SPLEEN, , FUNCTIONS OF SPLEEN, , Spleen is the largest lymphoid organ in the body and, it is highly vascular. It is situated in left hypochondrial, region, i.e. upper left part of the abdomen, behind the, stomach and just below the diaphragm. About 10% of, people have one or more accessory spleens which are, situated near the main spleen., Spleen is covered by an outer serous coat and, an inner fibromuscular capsule. From the capsule, the, trabeculae and trabecular network arise. All the three, structures, viz. capsule, trabeculae and trabecular, network contain collagen fibers, elastic fibers, smooth, muscle fibers and reticular cells. The parenchyma of, spleen is divided into red and white pulp., , 1. FORMATION OF BLOOD CELLS, , RED PULP, Red pulp consists of venous sinus and cords of structures, like blood cells, macrophages and mesenchymal cells., WHITE PULP, The structure of white pulp is similar to that of lymphoid, tissue. It has a central artery, which is surrounded by, splenic corpuscles or Malpighian corpuscles. These, corpuscles are formed by lymphatic sheath containing, lymphocytes and macrophages., , Spleen plays an important role in the hemopoietic, function in embryo. During the hepatic stage, spleen, produces blood cells along with liver. In myeloid stage,, it produces the blood cells along with liver and bone, marrow., 2. DESTRUCTION OF BLOOD CELLS, Older RBCs, lymphocytes and thrombocytes are, destroyed in the spleen. When the RBCs become old, (120 days), the cell membrane becomes more fragile., Diameter of most of the capillaries is less or equal to that, of RBC. The fragile old cells are destroyed while trying, to squeeze through the capillaries because, these cells, cannot withstand the stress of squeezing., Destruction occurs mostly in the capillaries of spleen, because the splenic capillaries have a thin lumen. So,, the spleen is known as ‘graveyard of RBCs’., 3. BLOOD RESERVOIR FUNCTION, In animals, spleen stores large amount of blood., However, this function is not significant in humans. But,, a large number of RBCs are stored in spleen. The RBCs
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154 Section 2 t Blood and Body Fluids, are released from spleen into circulation during the, emergency conditions like hypoxia and hemorrhage., , 6. Cysts in spleen, 7. Hodgkin’s disease, 8. Glandular fever., , 4. ROLE IN DEFENSE OF BODY, Spleen filters the blood by removing the microorganisms., The macrophages in splenic pulp destroy the microorganisms and other foreign bodies by phagocytosis., Spleen contains about 25% of T lymphocytes and, 15% of B lymphocytes and forms the site of antibody, production., , Effects of Splenomegaly, 1., 2., 3., 4., , Hemolysis resulting in anemia, Leukopenia, Thrombocytopenia, Increase in plasma volume., , HYPOSPLENISM AND ASPLENIA, , APPLIED PHYSIOLOGY, SPLENOMEGALY AND HYPERSPLENISM, Splenomegaly refers to enlargement of spleen. Increase, in the activities of spleen is called hypersplenism., Some diseases cause splenomegaly resulting in, hypersplenism., Diseases which cause splenomegaly:, 1. Infectious diseases such as malaria, typhoid and, tuberculosis, 2. Inflammatory diseases like rheumatoid arthritis, 3. Pernicious anemia, 4. Liver diseases, 5. Hematological disorders like spherocytosis, , Hyposplenism or hyposplenia refers to diminished, functioning of spleen. It occurs after partial removal of, spleen due to trauma or cyst. Asplenia means absence, of spleen. Functional asplenia means normal functions, of spleen. It occurs in the following conditions:, 1. Congenital absence of spleen function (congenital, asplenia)., 2. Acquired through surgical removal of spleen, (splenectomy)., 3. Acquired through some diseases, which destroy, spleen to such an extent that it becomes nonfunctional. This process is called autosplenectomy., The diseases which cause autosplenectomy are, sickle cell anemia and spherocytosis.
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Lymphatic System, and Lymph, , Chapter, , 26, , LYMPHATIC SYSTEM, , , , , ORGANIZATION, DRAINAGE, SITUATION, , LYMPH NODES, , , , , STRUCTURE, FUNCTIONS, APPLIED PHYSIOLOGY – SWELLING OF LYMPH NODES, , LYMPH, , , , , , FORMATION, RATE OF FLOW, COMPOSITION, FUNCTIONS, , LYMPHATIC SYSTEM, Lymphatic system is a closed system of lymph channels, or lymph vessels, through which lymph flows. It is a, one-way system and allows the lymph flow from tissue, spaces toward the blood., ORGANIZATION OF LYMPHATIC SYSTEM, Lymphatic system arises from tissue spaces as a, meshwork of delicate vessels. These vessels are called, lymph capillaries., , Lymph capillaries start from tissue spaces as, enlarged blind-ended terminals called capillary bulbs., These bulbs contain valves, which allow flow of lymph in, only one direction. There are some muscle fibers around, these bulbs. These muscle fibers cause contraction of, bulbs so that, lymph is pushed through the vessels., Lymph capillaries are lined by endothelial cells., Capillaries unite to form large lymphatic vessels., Lymphatic vessels become larger and larger because of, the joining of many tributaries along their course., The structure of lymph capillaries is slightly different, from that of the blood capillaries. Lymph capillaries are, , more porous and the cells lie overlapping on one another., This allows the fluid to move into the lymph capillaries, and not in the opposite direction., DRAINAGE OF LYMPHATIC SYSTEM, Larger lymph vessels ultimately form the right lymphatic, duct and thoracic duct. Right lymphatic duct opens into, right subclavian vein and the thoracic duct opens into, left subclavian vein. Thoracic duct drains the lymph from, more than two third of the tissue spaces in the body (Fig., 26.1)., SITUATION OF LYMPH VESSELS, Lymph vessels are situated in the following regions:, 1. Deeper layers of skin, 2. Subcutaneous tissues, 3. Diaphragm, 4. Wall of abdominal cavity, 5. Omentum, 6. Linings of respiratory tract except alveoli, 7. Linings of digestive tract, 8. Linings of urinary tract
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156 Section 2 t Blood and Body Fluids, Cortex, Cortex of lymph node consists of primary and secondary, lymphoid follicles. Primary follicle develops first. When, some antigens enter the body and reach the lymph, nodes, the cells of primary follicle proliferate. The active, proliferation of the cells occurs in a particular area of, the follicle called the germinal center. After proliferation, of cells, the primary follicles become the secondary, follicle. Cortex also contains some B lymphocytes,, which are usually aggregated into the primary follicles., Macrophages are also found in the cortex., Paracortex, Paracortex is in between the cortex and medulla., Paracortex contains T lymphocytes., Medulla, Medulla contains B and T lymphocytes and macrophages., Blood vessels of lymph node pass through medulla., Lymphatic Vessels to Lymph Node, , FIGURE 26.1: Lymph drainage. Blue area = Drained by right, lymphatic duct; Pink area = Drained by thoracic duct., , 9. Linings of genital tract, 10. Liver, 11. Heart., Lymph vessels are not present in the following, structures:, 1. Superficial layers of skin, 2. Central nervous system, 3. Cornea, 4. Bones, 5. Alveoli of lungs., , Lymph node receives lymph by one or two lymphatic, vessels called afferent vessels. Afferent vessels divide, into small channels. Lymph passes through afferent, vessels and small channels and reaches the cortex. It, circulates through cortex, paracortex and medulla of the, lymph node. From medulla, the lymph leaves the node, via one or two efferent vessels., Distribution of Lymph Nodes, Lymph nodes are present along the course of lymphatic, vessels in elbow, axilla, knee and groin. Lymph nodes, , LYMPH NODES, Lymph nodes are small glandular structures located in, the course of lymph vessels. The lymph nodes are also, called lymph glands or lymphatic nodes., STRUCTUTRE OF LYMPH NODES, Each lymph node constitutes masses of lymphatic, tissue, covered by a dense connective tissue capsule., The structures are arranged in three layers namely, cortex, paracortex and medulla (Fig. 26.2)., , FIGURE 26.2: Structure of a lymph node
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Chapter 26 t Lymphatic System and Lymph 157, are also present in certain points in abdomen, thorax, and neck, where many lymph vessels join., FUNCTIONS OF LYMPH NODES, Lymph nodes serve as filters which filter bacteria and, toxic substances from the lymph., Functions of the lymph nodes are:, 1. When lymph passes through the lymph nodes, it is, filtered, i.e. the water and electrolytes are removed., But, the proteins and lipids are retained in the, lymph., 2. Bacteria and other toxic substances are destroyed, by macrophages of lymph nodes. Because of this,, lymph nodes are called defense barriers., APPLIED PHYSIOLOGY – SWELLING, OF LYMPH NODES, During infection or any other processes in a particular, region of the body, activities of the lymph nodes in that, region increase. This causes swelling of the lymph nodes., Sometimes, the swollen lymph nodes cause pain., , Most common cause of swollen lymph nodes, is infection. Lymph nodes situated near an infected, area swell immediately. When the body recovers from, infection, the lymph nodes restore their original size, gradually, in one or two weeks., Causes for Lymph Node Swelling, 1. Skin infection of arm causes swelling of lymph nodes, in armpit., 2. Tonsillitis or throat infection causes swelling of, lymph nodes in neck., 3. Infection of genital organs or leg results in swelling, of lymph nodes in groin., 4. Viral infections such as glandular fever which affect, the whole body cause swelling of lymph nodes in, various parts of the body., 5. Cancer in a particular region may spread into the, nearby lymph nodes causing the swelling., Examples:, i. Throat cancer may spread into lymph nodes in, neck., , FIGURE 26.3: Composition of lymph
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158 Section 2 t Blood and Body Fluids, ii. Lung cancer may spread into lymph nodes in, chest., iii. Breast cancer may spread into lymph nodes in, armpit., iv. Intestinal cancer may spread into lymph nodes, in abdomen., v.. Lymphomas (cancer of lymphatic system) and, leukemia cause swelling of lymph nodes in many, parts of the body., , LYMPH, FORMATION OF LYMPH, Lymph is formed from interstitial fluid, due to the, permeability of lymph capillaries. When blood passes, via blood capillaries in the tissues, 9/10th of fluid passes, into venous end of capillaries from the arterial end., And, the remaining 1/10th of the fluid passes into lymph, capillaries, which have more permeability than blood, capillaries., So, when lymph passes through lymph capillaries,, the composition of lymph is more or less similar to that of, interstitial fluid including protein content. Proteins present, in the interstitial fluid cannot enter the blood capillaries, because of their larger size. So, these proteins enter, lymph vessels, which are permeable to large particles, also., Addition of Proteins and Fats, Tissue fluid in liver and gastrointestinal tract contains, more protein and lipid substances. So, proteins and lipids, enter the lymph vessels of liver and gastrointestinal tract, in large quantities. Thus, lymph in larger vessels has, more proteins and lipids., Concentration of Lymph, When the lymph passes through the lymph nodes, it is, concentrated because of absorption of water and the, , electrolytes. However, the proteins and lipids are not, absorbed., RATE OF LYMPH FLOW, About 120 mL of lymph flows into blood per hour. Out of, this, about 100 mL/hour flows through thoracic duct and, 20 mL/ hour flows through the right lymphatic duct., Factors Increasing the Flow of Lymph, Flow of lymph is promoted by the increase in:, 1. Interstitial fluid pressure., 2. Blood capillary pressure., 3. Surface area of lymph capillary by means of, dilatation., 4. Permeability of lymph capillaries., 5. Functional activities of tissues., COMPOSITION OF LYMPH, Usually, lymph is a clear and colorless fluid. It is formed, by 96% water and 4% solids. Some blood cells are also, present in lymph (Fig. 26.3)., FUNCTIONS OF LYMPH, 1. Important function of lymph is to return the proteins, from tissue spaces into blood., 2. It is responsible for redistribution of fluid in the body., 3. Bacteria, toxins and other foreign bodies are remov, ed from tissues via lymph., 4. Lymph flow is responsible for the maintenance of, structural and functional integrity of tissue. Obstruc, tion to lymph flow affects various tissues, particularly, myocardium, nephrons and hepatic cells., 5. Lymph flow serves as an important route for intestinal, fat absorption. This is why lymph appears milky after, a fatty meal., 6. It plays an important role in immunity by transport of, lymphocytes.
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Tissue Fluid and Edema, , Chapter, , 27, , DEFINITION, FUNCTIONS, FORMATION, , , , FILTRATION, REABSORPTION, , APPLIED PHYSIOLOGY – EDEMA, , , , , , , DEFINITION, TYPES, INTRACELLULAR EDEMA, EXTRACELLULAR EDEMA, PITTING AND NON-PITTING EDEMA, , DEFINITION, Tissue fluid is the medium in which cells are bathed. It is, otherwise known as interstitial fluid. It forms about 20%, of extracellular fluid (ECF)., , FUNCTIONS OF TISSUE FLUID, Because of the capillary membrane, there is no direct, contact between blood and cells. And, tissue fluid acts as, a medium for exchange of various substances between, the cells and blood in the capillary loop. Oxygen and, nutritive substances diffuse from the arterial end of, capillary through the tissue fluid and reach the cells., Carbon dioxide and waste materials diffuse from the, cells into the venous end of capillary through this fluid., , FORMATION OF TISSUE FLUID, Formation of tissue fluid involves two processes:, 1. Filtration., 2. Reabsorption., FILTRATION, Tissue fluid is formed by the process of filtration., Normally, the blood pressure (also called hydrostatic, , pressure) in arterial end of the capillary is about 30, , mm Hg. This hydrostatic pressure is the driving force, for filtration of water and other substances from blood, into tissue spaces. Along the course of the capillary, the, pressure falls gradually and it is about 15 mm Hg at the, venous end., Capillary membrane is not permeable to the large, molecules, particularly the plasma proteins. So, these, proteins remain in the blood and exert a pressure called, oncotic pressure or colloidal osmotic pressure. It is, about 25 mm Hg., Osmotic pressure is constant throughout the, circulatory system and it is an opposing force for the, filtration of water and other materials from capillary blood, into the tissue space. However, the hydrostatic pressure, in the arterial end of the capillary (30 mm Hg) is greater, than the osmotic pressure. And, the net filtration pressure, of 5 mm Hg is responsible for continuous filtration (Fig., 27.1)., Starling Hypothesis, Determination of net filtration pressure is based on, Starling hypothesis. Starling hypothesis states that the, net filtration through capillary membrane is proportional, to the hydrostatic pressure difference across the
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160 Section 2 t Blood and Body Fluids, membrane minus the oncotic pressure difference. These, pressures are called Starling forces (Refer Chapter 52, for more details)., , is specific areas of the body such as abdomen, lungs, and extremities like feet, ankles and legs. Accumulation, of fluid may be inside or outside the cell., , REABSORPTION, , TYPES OF EDEMA, , Fluid filtered at the arterial end of capillaries is reabsorbed, back into the blood at the venous end of capillaries. Here, also, the pressure gradient plays an important role. At, the venous end of capillaries, the hydrostatic pressure, is less (15 mm Hg) and the oncotic pressure is more (25, mm Hg). Due to the pressure gradient of 10 mm Hg, the, fluid is reabsorbed along with waste materials from the, tissue fluid into the capillaries. About 10% of filtered fluid, enters the lymphatic vessels., Thus, the process of filtration at the arterial end of, the capillaries helps in the formation of tissue fluids and, the process of reabsorption at the venous end helps to, maintain the volume of tissue fluid., , Edema is classified into two types, depending upon the, body fluid compartment where accumulation of excess, fluid occurs:, 1. Intracellular edema, 2. Extracellular edema., INTRACELLULAR EDEMA, , APPLIED PHYSIOLOGY – EDEMA, , 1. Edema due to Malnutrition, , DEFINITION, Edema is defined as the swelling caused by excessive, accumulation of fluid in the tissues. It may be generalized, or local. Edema that involves the entire body is called, generalized edema. Local edema is the one that occurs, , Intracellular edema is the accumulation of fluid inside, the cell. It occurs because of three reasons:, 1. Malnutrition, 2. Poor metabolism, 3. Inflammation of the tissues., , Malnutrition occurs because of poor intake of food or, poor circulatory system, through which the nutritive, substances are supplied. Due to the lack of nutrition,, the ionic pumps of the cell membrane are depressed, leading to poor exchange of ions. Especially, the sodium, ions leaking into the cells cannot be pumped out. Excess, , FIGURE 27.1: Formation of tissue fluid. Plasma proteins remain inside the blood capillary as the capillary, membrane is not permeable to plasma proteins.
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Chapter 27 t Tissue Fluid and Edema 161, sodium inside the cells causes endosmosis, resulting in, intracellular edema., 2. Edema due to Poor Metabolism, Poor metabolism is caused by poor blood supply. Poor, blood supply leads to lack of oxygen. It results in poor, function of cell membrane and edema, as explained, above., 3. Edema due to Inflammation of Tissues, During inflammation of the tissues, usually the, permeability of cell membrane increases. This causes, the movement of many ions, including sodium into the, cells resulting in endosmosis and intracellular edema., EXTRACELLULAR EDEMA, Extracellular edema is defined as the accumulation of, fluid outside the cell., Causes for extracellular edema, 1. Abnormal leakage of fluid from capillaries into, interstitial space., 2. Obstruction of lymphatic vessels that prevents fluid, return from interstitium to blood., Conditions which lead to extracellular edema, 1., 2., 3., 4., 5., , Heart failure., Renal disease., Decreased amount of plasma proteins., Lymphatic obstruction., Increased endothelial permeability., , 1. Edema due to Heart Failure, Edema occurs in heart failure because of various, reasons such as:, i. Failure of heart to pump blood: Failure of the heart, to pump blood from veins to arteries increases, venous pressure and capillary pressure. This, leads to increased capillary permeability and, leakage of fluid from blood into interstitial fluid,, causing extracellular edema., ii. Fall in blood pressure during heart failure: It, decreases the glomerular filtration rate in the, kidneys, resulting in sodium and water retention., So, the volume of blood and body fluid increases., This in turn increases the capillary hydrostatic, pressure. These two factors together increase, the accumulation of fluid causing extracellular, edema., iii. Low blood supply to kidneys during heart, failure: It increases renin secretion, which in turn, , increases aldosterone secretion. Aldosterone, increases the reabsorption of sodium and water, from renal tubules into ECF resulting in the, development of extracellular edema., Pulmonary Edema, Pulmonary edema is the accumulation of fluid in, pulmonary interstitium. In left heart failure, the blood, is easily pumped into pulmonary circulation by right, ventricle. However, the blood cannot return from lungs, to left side of the heart because of weakness of this, side of the heart. This increases pulmonary vascular, pressure leading to leakage of fluid from capillaries into, pulmonary interstitium. It causes pulmonary edema, which can be life threatening., 2. Edema due to Renal Diseases –, Generalized Edema, In renal disease, the kidneys fail to excrete water and, electrolytes particularly sodium, leading to retention of, water and electrolytes. So, the fluid leaks from blood into, interstitial space causing extracellular edema. Initially,, the edema develops in the legs, but later it progresses, to the entire body (generalized edema)., 3. Edema due to Decreased Amount, of Plasma Proteins, When the amount of plasma proteins decreases, the, colloidal osmotic pressure decreases. Because of this,, the permeability of the capillary increases, resulting in, increased capillary filtration. So, more amount of water, leaks out of the capillary. It accumulates in the tissue, spaces resulting in extracellular edema., Amount of plasma proteins decreases during, the conditions like malnutrition, liver diseases, renal, diseases, burns and inflammation., 4. Edema due to Lymphatic, Obstruction – Lymphedema, Lymphedema is the edema caused by lymphatic, obstruction. It is common in filariasis. During this, disease, the parasitic worms live in the lymphatics and, obstruct the drainage of lymph. Accumulation of lymph, along with cellular reactions leads to swelling that is very, prominent in legs and scrotum. Repeated obstruction of, lymphatic drainage in these regions results in fibrosis, and development of elephantiasis., Elephantiasis, Elephantiasis is a disorder of lymphatic system,, characterized by thickening of skin and extreme
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162 Section 2 t Blood and Body Fluids, enlargement of the affected area, most commonly, limbs (legs), genitals, certain areas of trunk and parts, of head., 5. Edema due to Increased Endothelial Permeability, The permeability of the capillary endothelium increases, in conditions like burns, inflammation, trauma, allergic, reactions and immunologic reactions, which lead to, oozing out of fluid. This fluid accumulates leading to, development of edema., PITTING AND NON-PITTING EDEMA, Interstitial fluid is present in the form of a gel that is, almost like a semisolid substance. It is because the, interstitial fluid is not present as fluid but is bound in, a proteoglycan meshwork. It does not allow any free, space for the fluid movement except for a diameter of, about a few hundredths of a micron., , Normal volume of interstitial fluid is 12 L and it exerts, a negative pressure of about 3 mm Hg. It applies a slight, suction effect and holds the tissues together. However,, in abnormal conditions, where the interstitial fluid volume, increases enormously, the pressure becomes positive., Most of the fluid becomes free fluid that is not bound to, proteoglycan meshwork. It flows freely through tissue, spaces, producing a swelling called edema. This type, of edema is known as pitting edema because, when, this area is pressed with the finger, displacement of fluid, occurs producing a depression or pit. When the finger, is removed, the pit remains for few seconds, sometimes, as long as one minute, till the fluid flows back into that, area., Edema also develops due to swelling of the cells or, clotting of interstitial fluid in the presence of fibrinogen., This is called non-pitting edema because, it is hard and, a pit is not formed by pressing.
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Questions in Blood and Body Fluids 163, , QUESTIONS IN BLOOD AND BODY FLUIDS, , LONG QUESTIONS, 1. What are the compartments of body fluid?, Enumerate the differences between ECF and ICF, and explain the measurement of ECF volume., 2. What is indicator dilution technique? How is it, applied in the measurement of total body water?, Describe dehydration briefly., 3. Give a detailed account of erythropoiesis., 4. Define erythropoiesis. List the different stages of, erythropoiesis. Describe the changes which take, place in each stage and the factors necessary for, erythropoiesis., 5. Describe the morphology, development and, functions of leukocytes., 6. Describe the development of cell-mediated, immunity., 7. Describe the development of humoral immunity., 8. Define blood coagulation. Describe the, mechanisms involved in coagulation. Add a note, on anticoagulants., 9. Enumerate the factors involved in blood, coagulation and describe the intrinsic mechanism, of coagulation., 10. Give an account of extrinsic mechanism of, coagulation of blood. Give a brief description of, bleeding disorders., 11. What is normal blood volume and what are the, factors regulating blood volume? Describe the, measurement of blood volume and give a brief, account of edema., 12. Give an account of tissue fluid. Add a note on, edema., , SHORT QUESTIONS, 1., 2., 3., 4., 5., 6., 7., 8., 9., 10., 11., 12., 13., , Dye or indicator dilution technique., Measurement of total body water., Measurement of ECF volume., Measurement of ICF volume., Measurement of blood volume., Measurement of plasma volume., Dehydration., Water intoxication., Functions of blood., Plasma proteins., Plasmapheresis., Functions of RBCs., Fate of RBCs., , 14., 15., 16., 17., 18., 19., 20., 21., 22., 23., 24., 25., 26., 27., 28., 29., 30., 31., 32., 33., 34., 35., 36., 37., 38., 39., 40., 41., 42., 43., 44., 45., 46., 47., 48., 49., 50., 51., 52., 53., 54., 55., 56., 57., 58., 59., 60., , Lifespan of RBCs., Physiological variations of RBC count., Polycythemia., Stem cells., Factors necessary for erythropoiesis., Destruction of hemoglobin., Abnormal hemoglobin., Abnormal hemoglobin derivatives., Iron metabolism., Pernicious anemia., Erythrocyte sedimentation rate., Packed cell volume or hematocrit., Anemia., Blood indices., Hemolysins., Types and morphology WBCs., Functions of WBCs., T lymphocytes., B lymphocytes., Role of macrophages/antigen-presenting cells in, immunity., Immunoglobulins or antibodies., Immune deficiency diseases., Autoimmune diseases., Immunization., Cytokines., Platelets., Hemostasis., Fibrinolysis., Tests for coagulation., Anticoagulants., Procoagulants., Bleeding disorders., Hemophilia., Purpura., Thrombosis., ABO blood groups., Rh factor., Transfusion reactions., Hemolytic disease of the newborn/, erythroblastosis fetalis., Exchange transfusion, Blood volume., Reticuloendothelial system or tissue macrophage., Functions of spleen., Lymph., Lymph nodes., Tissue fluid., Edema.
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Section, , 3, , 28., 29., 30., 31., 32., 33., 34., 35., , Muscle Physiology, , Classification of Muscles ......................................................................... 167, Structure of Skeletal Muscle ................................................................... 169, Properties of Skeletal Muscle .................................................................. 176, Changes during Muscular Contraction .................................................... 188, Neuromuscular Junction ......................................................................... 200, Smooth Muscle ....................................................................................... 204, Electromyogram and Disorders of Skeletal Muscle ................................ 210, Endurance of Muscle .............................................................................. 214
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Classification of Muscles, , Chapter, , 28, , DEPENDING UPON STRIATIONS, DEPENDING UPON CONTROL, DEPENDING UPON SITUATION, , Human body has more than 600 muscles. Muscles, perform many useful functions and help us in doing, everything in day-to-day life. Muscles are classified by, three different methods, based on different factors:, I. Depending upon the presence or absence of, striations, II. Depending upon the control, III. Depending upon the situation., , 1. Voluntary Muscle, , DEPENDING UPON STRIATIONS, , 2. Involuntary Muscle, , Depending upon the presence or absence of cross, striations, the muscles are divided into two groups:, 1. Striated muscle, 2. Non-striated muscle., , Muscle that cannot be controlled by the will is called, involuntary muscle. Cardiac muscle and smooth muscle, are involuntary muscles. These muscles are innervated, by autonomic nerves., , 1. Striated Muscle, , DEPENDING UPON SITUATION, , Striated muscle is the muscle which has a large number, of cross-striations (transverse lines). Skeletal muscle, and cardiac muscle belong to this category., , Depending upon situation, the muscles are classified, into three types:, 1. Skeletal muscle, 2. Cardiac muscle, 3. Smooth muscle., Features of these muscles are given in Table 28.1., , 2. Non-striated Muscle, Muscle which does not have cross-striations is called, non-striated muscle. It is also called plain muscle or, smooth muscle. It is found in the wall of the visceral, organs., , DEPENDING UPON CONTROL, Depending upon control, the muscles are classified into, two types:, , 1. Voluntary muscle, 2. Involuntary muscle., , Voluntary muscle is the muscle that is controlled by the, will. Skeletal muscles are the voluntary muscles. These, muscles are innervated by somatic nerves., , 1. Skeletal Muscle, Skeletal muscle is situated in association with bones, forming the skeletal system. The skeletal muscles, form 40% to 50% of body mass and are voluntary, and striated. These muscles are supplied by somatic, nerves.
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168 Section 3 t Muscle Physiology, TABLE 28.1: Features of skeletal, cardiac and smooth muscle fibers, Features, , Skeletal muscle, , Cardiac muscle, , Smooth muscle, , Location, , In association with bones, , In the heart, , In the visceral organs, , Shape, , Cylindrical and unbranched, , Branched, , Spindle-shaped, unbranched, , Length, , 1 cm to 4 cm, , 80 µ to 100 μ, , 50 µ to 200 μ, , Diameter, , 10 µ to 100 μ, , 15 µ to 20 μ, , 2 µ to 5 μ, , Number of nucleus, , More than one, , One, , One, , Cross-striations, , Present, , Present, , Absent, , Myofibrils, , Present, , Present, , Absent, , Sarcomere, , Present, , Present, , Absent, , Troponin, , Present, , Present, , Absent, , Sarcotubular system, , Well developed, , Well developed, , Poorly developed, , ‘T’ tubules, , Long and thin, , Short and broad, , Absent, , Depolarization, , Upon stimulation, , Spontaneous, , Spontaneous, , Fatigue, , Possible, , Not possible, , Not possible, , Summation, , Possible, , Not possible, , Possible, , Tetanus, , Possible, , Not possible, , Possible, , Resting membrane potential, , Stable, , Stable, , Unstable, , For trigger of contraction,, calcium binds with, , Troponin, , Troponin, , Calmodulin, , Source of calcium, , Sarcoplasmic reticulum, , Sarcoplasmic reticulum, , Extracellular, , Speed of contraction, , Fast, , Intermediate, , Slow, , Neuromuscular junction, , Well defined, , Not well defined, , Not well defined, , Action, , Voluntary action, , Involuntary action, , Involuntary action, , Control, , Only neurogenic, , Myogenic, , Neurogenic and myogenic, , Nerve supply, , Somatic nerves, , Autonomic nerves, , Autonomic nerves, , Fibers of the skeletal muscles are arranged in, parallel. In most of the skeletal muscles, muscle fibers, are attached to tendons on either end. Skeletal muscles, are anchored to the bones by the tendons., 2. Cardiac Muscle, Cardiac muscle forms the musculature of the heart., These muscles are striated and involuntary. Cardiac, muscles are supplied by autonomic nerve fibers., , 3. Smooth Muscle, Smooth muscle is situated in association with viscera. It, is also called visceral muscle. It is different from skeletal, and cardiac muscles because of the absence of crossstriations, hence the name smooth muscle. Smooth, muscle is supplied by autonomic nerve fibers. Smooth, muscles form the main contractile units of wall of the, various visceral organs.
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Structure of Skeletal Muscle, , Chapter, , 29, , MUSCLE MASS, MUSCLE FIBER, MYOFIBRIL, , , MICROSCOPIC STRUCTURE, , SARCOMERE, , , ELECTRON MICROSCOPIC STUDY, , CONTRACTILE ELEMENTS (PROTEINS) OF MUSCLE, , , , , , MYOSIN MOLECULE, ACTIN MOLECULE, TROPOMYOSIN, TROPONIN, , OTHER PROTEINS OF THE MUSCLE, SARCOTUBULAR SYSTEM, , , , STRUCTURES, FUNCTIONS, , COMPOSITION OF MUSCLE, , MUSCLE MASS, , MUSCLE FIBER, , Muscle mass or muscle tissue is made up of a large, number of individual muscle cells or myocytes. The, muscle cells are commonly called muscle fibers because, these cells are long and slender in appearance. Skeletal, muscle fibers are multinucleated and are arranged, parallel to one another with some connective tissue in, between (Fig. 29.1)., Muscle mass is separated from the neighboring, tissues by a thick fibrous tissue layer known as fascia., Beneath the fascia, muscle is covered by a connective, tissue sheath called epimysium. In the muscle, the, muscle fibers are arranged in various groups called, bundles or fasciculi. Connective tissue sheath that, covers each fasciculus is called perimysium. Each, muscle fiber is covered by a connective tissue layer, called the endomysium (Fig. 29.2)., , Each muscle cell or muscle fiber is cylindrical in shape., Average length of the fiber is 3 cm. It varies between, 1 cm and 4 cm, depending upon the length of the, muscle. The diameter of the muscle fiber varies from, 10 µ to 100 µ. The diameter varies in a single muscle., Muscle fibers are attached to a tough cord of, connective tissue called tendon. Tendon is in turn, attached to the bone. Tendon of some muscles is thin,, flat and stretched but tough. Such type of tendon is, called aponeurosis., Each muscle fiber is enclosed by a cell membrane, called plasma membrane, that lies beneath the endomy, sium. It is also called sarcolemma (Fig. 29.3). Cytoplasm, of the muscle is known as sarcoplasm.
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170 Section 3 t Muscle Physiology, , FIGURE 29.1: Structure of a skeletal muscle, , Structures embedded within the sarcoplasm are:, Nuclei, Myofibril, Golgi apparatus, Mitochondria, Sarcoplasmic reticulum, Ribosomes, Glycogen droplets, Occasional lipid droplets., Each muscle fiber has got one or more nuclei. In long, muscle fibers, many nuclei are seen. Nuclei are oval or, elongated and situated just beneath the sarcolemma., Usually in other cells, the nucleus is in the interior of, the cell., All the organelles of muscle fiber have the same, functions as those of other cells., 1., 2., 3., 4., 5., 6., 7., 8., , MYOFIBRIL, Myofibrils or myofibrillae are the fine parallel filaments, present in sarcoplasm of the muscle cell. Myofibrils run, through the entire length of the muscle fiber., In the cross-section of a muscle fiber, the myofibrils, appear like small distinct dots within the sarcoplasm., Diameter of the myofibril is 0.2 to 2 µ. The length of, a myofibril varies between 1 cm and 4 cm, depending, upon the length of the muscle fiber (Table 29.1)., In some muscle fibers, some of the myofibrils are, arranged in groups called Cohnheim’s areas or fields., , FIGURE 29.2: Diagram showing. A. Skeletal muscle mass;, B. Crosssection of muscle; C. One muscle fasciculus., , MICROSCOPIC STRUCTURE OF A MYOFIBRIL, Light microscopic studies show that, each myofibril, consists of a number of two alternating bands which, are also called the sections, segments or disks. These, bands are formed by muscle proteins., The two bands are:, 1. Light band or ‘I’ band., 2. Dark band or ‘A’ band.
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Chapter 29 t Structure of Skeletal Muscle 171, , SARCOMERE, Definition, Sarcomere is defined as the structural and functional, unit of a skeletal muscle. It is also called the basic, contractile unit of the muscle., Extent, Each sarcomere extends between two ‘Z’ lines, of myofibril. Thus, each myofibril contains many, sarcomeres arranged in series throughout its length., When the muscle is in relaxed state, the average length, of each sarcomere is 2 to 3 µ., FIGURE 29.3: A. One muscle cell; B. One myofibril., , Light Band or ‘I’ Band, Light band is called ‘I’ (isotropic) band because it, is isotropic to polarized light. When polarized light is, passed through the muscle fiber at this area, light rays, are refracted at the same angle., Dark Band or ‘A’ Band, Dark band is called ‘A’ (anisotropic) band because it, is anisotropic to polarized light. When polarized light is, passed through the muscle fiber at this area, the light, rays are refracted at different directions (An = not; iso, = it; trops = turning). Dark band is also called ‘Q’ disk, (Querscheibe = cross disk)., In an intact muscle fiber, ‘I’ band and ‘A’ band of, the adjacent myofibrils are placed side-by-side. It gives, the appearance of characteristic crossstriations in the, muscle fiber., I band is divided into two portions, by means of, a narrow and dark line called ‘Z’ line or ‘Z’ disk (in, German, zwischenscheibe = between disks). The ‘Z’, line is formed by a protein disk, which does not permit, passage of light. The portion of myofibril in between two, ‘Z’ lines is called sarcomere., , Components, Each myofibril consists of an alternate dark ‘A’ band and, light ‘I’ band (Fig. 29.4). In the middle of ‘A’ band, there is, a light area called ‘H’ zone (H = hell = light – in German,, H = Henson – discoverer). In the middle of ‘H’ zone lies, the middle part of myosin filament. This is called ‘M’ line, (in German-mittel = middle). ‘M’ line is formed by myosin, binding proteins., ELECTRON MICROSCOPIC STUDY, OF SARCOMERE, Electron microscopic studies reveal that the sarcomere, consists of many threadlike structures called, myofilaments., , Myofilaments are of two types:, 1. Actin filaments, 2. Myosin filaments., , TABLE 29.1: Dimensions of structures in skeletal muscle, Structure, , Length, , Diameter, , Muscle fiber, , 1 cm to 4 cm, , 10 µ to 100 µ, , Myofibril, , 1 cm to 4 cm, , 0.2 µ to 2 µ, , Actin filament, , 1µ, , 20 Å, , Myosin filament, , 1.5 μ, , 115 Å, , FIGURE 29.4: Sarcomere. A = A band, I = I band.
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172 Section 3 t Muscle Physiology, Actin Filaments, Actin filaments are the thin filaments with a diameter of, 20 Å and a length of 1 µ. These filaments extend from, either side of the ‘Z’ lines, run across ‘I’ band and enter, into ‘A’ band up to ‘H’ zone., Myosin Filaments, Myosin filaments are thick filaments with a diameter of, 115 Å and a length of 1.5 µ. These filaments are situated, in ‘A’ band., Cross-bridges, Some lateral processes (projections) called cross, bridges arise from each myosin filament. These bridges, have enlarged structures called myosin heads at their, tips. Myosin heads attach themselves to actin filaments., These heads pull the actin filaments during contraction, of the muscle, by means of a mechanism called sliding, mechanism or ratchet mechanism., During the contraction of the muscle, the actin, filaments glide down between the myosin filaments, towards the center of ‘H’ zone and approach the, corresponding actin filaments from the next ‘Z’ line (Fig., 29.5). The ‘Z’ lines also approach the ends of myosin, , filaments, so that the ‘H’ zone and ‘I’ bands are shortened, during contraction of the muscle. During the relaxation, of the muscle, the actin filaments and ‘Z’ lines come, back to the original position., , CONTRACTILE ELEMENTS, (PROTEINS) OF MUSCLE, Myosin filaments are formed by myosin molecules., Actin filaments are formed by three types of proteins, called actin, tropomyosin and troponin. These four, proteins together constitute the contractile proteins or, the contractile elements of the muscle., MYOSIN MOLECULE, Each myosin filament consists of about 200 myosin, molecules. Though about 18 classes of myosin are, identified, only myosin II is present in the sarcomere., Myosin II is a globulin with a molecular weight, of 480,000. Each myosin molecule is made up of 6, polypeptide chains, of which two are heavy chains and, four are light chains (Fig. 29.5). Molecular weight of, each heavy chain is 200,000 (2 × 200,000 = 400,000)., Molecular weight of each light chain is 20,000 (4 ×, 20,000 = 80,000). Thus, total molecular weight of each, myosin molecule is 480,000 (400,000 + 80,000)., Portions of Myosin Molecule, Each myosin molecule has two portions:, 1. Tail portion, 2. Head portion., Tail portion of myosin molecule, It is made up of two heavy chains, which twist around, each other in the form of a double helix (Fig. 29.6)., Head portion of myosin molecule, At one end of the double helix, both the heavy chains, turn away in opposite directions and form the globular, head portion. Thus the head portion has two parts. Two, light chains are attached to each part of the head portion, of myosin molecule (Fig. 29.6)., , FIGURE 29.5: Sarcomere in resting muscle A. Contracted, muscle; B. During contraction; Z lines come close, H zone and, I band are reduced and no change in A band., , FIGURE 29.6: Diagram showing myosin filament., ATP = Adenosine triphosphate.
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Chapter 29 t Structure of Skeletal Muscle 173, Each myosin head has two attachment sites. One, site is for actin filament and the other one is for one, ATP molecule (Fig. 29.7). Myosin head is absent in the, central part of myosin filament, i.e. in the ‘H’ zone., ACTIN MOLECULE, Actin molecules are the major constituents of the thin, actin filaments. Each actin molecule is called F-actin, and it is the polymer of a small protein known as G-actin., There are about 300 to 400 actin molecules in each, actin filament. The molecular weight of each molecule, is 42,000. The actin molecules in the actin filament are, also arranged in the form of a double helix., Each Factin molecule has an active site to which, the myosin head is attached (Fig. 29.8)., TROPOMYOSIN, , TROPONIN, It is formed by three subunits:, 1. Troponin I, which is attached to Factin, 2. Troponin T, which is attached to tropomyosin, 3. Troponin C, which is attached to calcium ions., , OTHER PROTEINS OF THE MUSCLE, In addition to the contractile proteins, the sarcomere, contains several other proteins such as:, 1. Actinin, which attaches actin filament to ‘Z’ line., 2. Desmin, which binds ‘Z’ line with sarcolemma., 3. Nebulin, which runs in close association with and, parallel to actin filaments., 4. Titin, a large protein connecting ‘M’ line and ‘Z’ line., Each titin molecule forms scaffolding (framework), for sarcomere and provides elasticity to the muscle., , About 40 to 60 tropomyosin molecules are situated, along the double helix strand of actin filament. Each, tropomyosin molecule has the molecular weight, of 70,000. In relaxed condition of the muscle, the, tropomyosin molecules cover all the active sites of, Factin molecules., , FIGURE 29.7: Myosin molecule formed by two heavy chains, and four light chains of polypeptides, , FIGURE 29.8: Part of actin filament., Troponin has three subunits, T, C and I., , FIGURE 29.9: Diagram showing the relation between, sarcotubular system and parts of sarcomere. Only few, myofilaments are shown in the myofibril drawn on the right, side of the diagram.
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174 Section 3 t Muscle Physiology, , FIGURE 29.10: Composition of skeletal muscle, , When the muscle is stretched, the titin unfolds itself., However, if the stretching is more, it offers resistance, and protects the sarcomere from overstretching., 5. Dystrophin, a rodshaped large protein that connects, actin filament to dystroglycan. Dystroglycan is a, transmembrane protein, present in the sarcolemma., Dystrophin and dystroglycan form dystrophin, dystroglycan or dystrophinglycoprotein complex., , SARCOTUBULAR SYSTEM, Sarcotubular system is a system of membranous, structures in the form of vesicles and tubules in the, sarcoplasm of the muscle fiber. It surrounds the myofibrils embedded in the sarcoplasm (Fig. 29.9)., STRUCTURES CONSTITUTING THE, SARCOTUBULAR SYSTEM, Sarcotubular system is formed mainly by two types of, structures:, , 1. Ttubules, 2. Ltubules or sarcoplasmic reticulum., T-Tubules, Ttubules or transverse tubules are narrow tubules, formed by the invagination of the sarcolemma. These, tubules penetrate all the way from one side of the, muscle fiber to an another side. That is, these tubules, penetrate the muscle cell through and through. Because, of their origin from sarcolemma, the Ttubules open to, the exterior of the muscle cell. Therefore, the ECF runs, through their lumen., L-Tubules or Sarcoplasmic Reticulum, Ltubules or longitudinal tubules are the closed tubules, that run in long axis of the muscle fiber, forming, sarcoplasmic reticulum. These tubules form a closed, tubular system around each myofibril and do not open, to exterior like Ttubules.
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Chapter 29 t Structure of Skeletal Muscle 175, Ltubules correspond to the endoplasmic reticulum, of other cells. At regular intervals, throughout the length, of the myofibrils, the L-tubules dilate to form a pair, of lateral sacs called terminal cisternae. Each pair of, terminal cisternae is in close contact with Ttubule. The, Ttubule along with the cisternae on either side is called, the triad of skeletal muscle., In human skeletal muscle, the triads are situated at, the junction between ‘A’ band and ‘I’ band. Calcium ions, are stored in Ltubule and the amount of calcium ions is, more in cisternae., FUNCTIONS OF SARCOTUBULAR SYSTEM, Function of T-Tubules, Ttubules are responsible for rapid transmission of, impulse in the form of action potential from sarcolemma, to the myofibrils. When muscle is stimulated, the action, potential develops in sarcolemma and spreads through, it. Since Ttubules are the continuation of sarcolemma,, the action potential passes through them and reaches, the interior of the muscle fiber rapidly., , Function of L-Tubules, Ltubules store a large quantity of calcium ions. When, action potential reaches the cisternae of Ltubule, the, calcium ions are released into the sarcoplasm. Calcium, ions trigger the processes involved in contraction of the, muscle. The process by which the calcium ions cause, contraction of muscle is called excitationcontraction, coupling (Chapter 31)., , COMPOSITION OF MUSCLE, Skeletal muscle is formed by 75% of water and, 25% of solids. Solids are 20% of proteins and 5% of, organic substances other than proteins and inorganic, substances (Fig. 29.10)., Among the proteins, the first eight proteins are, already described in this chapter. Myoglobin is present, in sarcoplasm. It is also called myohemoglobin. Its, function is similar to that of hemoglobin, that is, to carry, oxygen. It is a conjugated protein with a molecular, weight of 17,000.
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Properties of, Skeletal Muscle, , Chapter, , 30, , EXCITABILITY, , , , , , DEFINITIONS, TYPES OF STIMULUS, QUALITIES OF STIMULUS, EXCITABILITY CURVE OR STRENGTH-DURATION CURVE, , CONTRACTILITY, , , , , , , , TYPES OF CONTRACTION, SIMPLE MUSCLE CONTRACTION OR TWITCH OR CURVE, CONTRACTION TIME – RED MUSCLE AND PALE MUSCLE, FACTORS AFFECTING FORCE OF CONTRACTION, LENGTH-TENSION RELATIONSHIP, REFRACTORY PERIOD, , MUSCLE TONE, , , , , DEFINITION, MAINTENANCE OF MUSCLE TONE, APPLIED PHYSIOLOGY – ABNORMALITIES OF MUSCLE TONE, , EXCITABILITY, DEFINITIONS, Excitability, Excitability is defined as the reaction or response of a, tissue to irritation or stimulatiosn. It is a physicochemical, change., Stimulus, Stimulus is the change in environment. It is defined as, an agent or influence or act, which causes the response, in an excitable tissue., TYPES OF STIMULUS, Stimuli, which can excite the tissue are of four types :, 1. Mechanical stimulus (pinching), 2. Electrical stimulus (electric shock), , 3. Thermal stimulus (applying heated glass rod or ice, piece), 4. Chemical stimulus (applying chemical substances, like acids)., Electrical stimulus is commonly used for experimental, purposes because of the following reasons:, i. It can be handled easily, ii. Intensity (strength) of stimulus can be easily, adjusted, iii. Duration of stimulus can be easily adjusted, iv. Stimulus can be applied to limited (small) area, on the tissues, v. Damage caused to tissues is nil or least., QUALITIES OF STIMULUS, To excite a tissue, the stimulus must possess two, characters:, 1. Intensity or strength, 2. Duration.
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Chapter 30 t Properties of Skeletal Muscle 177, 1. Intensity, , Method to Obtain the Curve, , Intensity or strength of a stimulus is of five types:, i. Subminimal stimulus, ii. Minimal stimulus, iii. Submaximal stimulus, iv. Maximal stimulus, v. Supramaximal stimulus., Stimulus whose strength (or voltage) is sufficient to, excite the tissue is called threshold or liminal or minimal, stimulus. Other details are given under the heading, ‘Factors affecting force of contraction’ in this chapter., , In this curve, the strength of the stimulus is plotted, (in volts) vertically and the duration (in milliseconds), horizontally., To start with, a stimulus with higher strength or, voltage (4 or 5 volt) is applied. The minimum duration,, taken by the stimulus with particular strength to excite, the tissue is noted. The strength and duration are, plotted in the graph. Then, the strength of the stimulus, is decreased and the duration is determined. Like this,, the voltage is decreased gradually and the duration is, determined every time. All the results are plotted and, the curve is obtained., , 2. Duration, Whatever may be the strength of the stimulus, it must, be applied for a minimum duration to excite the tissue., However, the duration of a stimulus depends upon, the strength of the stimulus. For a weak stimulus,, the duration is longer and for a stronger stimulus, the, duration is shorter. The relationship between the strength, and duration of stimulus is demonstrated by means of, excitability curve or strength-duration curve., EXCITABILITY CURVE OR, STRENGTH-DURATION CURVE, Excitability curve is the graph that demonstrates the, exact relationship between the strength and the duration, of a stimulus. So, it is also called the strength-duration, curve (Fig. 30.1)., , Characteristic Features of the Curve, The shape of the curve is similar in almost all the, excitable tissues. Following are the important points to, be observed in the excitability curve:, 1. Rheobase, 2. Utilization time, 3. Chronaxie., 1. Rheobase, Rheobase is the minimum strength (voltage) of stimulus,, which can excite the tissue. The voltage below this, cannot excite the tissue, whatever may be the duration, of the stimulus., 2. Utilization Time, Utilization time is the minimum time required for rheobasic strength of stimulus (threshold strength) to excite, the tissue., 3. Chronaxie, Chronaxie is the minimum time required for a stimulus, with double the rheobasic strength (voltage) to excite, the tissue., Importance of chronaxie, Measurement of chronaxie determines the excitability, of the tissues. It is used to compare the excitability in, different tissues. Longer the chronaxie, lesser is the, excitability., Normal chronaxie, In human skeletal muscles : 0.08 to 0.32 milliseconds., In frog skeletal muscle, : 3 milliseconds., Variations in chronaxie, , FIGURE 30.1: Strength–duration curve. R = Rheobase,, UT = Utilization time, C = Chronaxie., , Chronaxie is:, 1. Ten times more in skeletal muscles of infants than in, the skeletal muscles of adults
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178 Section 3 t Muscle Physiology, 2. Shorter in red muscles than in pale muscles, 3. Shorter in warm-blooded (homeothermic) animals, than in cold-blooded (poikilothermic) animals, 4. Shortened during increased temperature and, prolonged during cold temperature, 5. Longer in paralyzed muscles than in normal, muscle, 6. Prolonged gradually during progressive neural, diseases., , Simple contraction of the muscle is called simple, muscle twitch and the graphical recording of this is, called simple muscle curve., Important Points in Simple Muscle Curve, , Contractility is the response of the muscle to a stimulus., Contraction is defined as the internal events of muscle, with change in either length or tension of the muscle, fibers., , Four points are to be observed in simple muscle curve:, 1. Point of stimulus (PS): The time when the stimulus, is applied., 2. Point of contraction (PC): The time when muscle, begins to contract., 3. Point of maximum contraction (PMC): The point up, to which the muscle contracts. It also indicates the, beginning of relaxation of the muscle., 4. Point of maximum relaxation (PMR): The point when, muscle relaxes completely., , TYPES OF CONTRACTION, , Periods of Simple Muscle Curve, , Muscular contraction is classified into two types based, on change in the length of muscle fibers or tension of, the muscle:, 1. Isotonic contraction, 2. Isometric contraction., , All the four points mentioned above divide the entire, simple muscle curve into three periods:, 1. Latent period (LP), 2. Contraction period (CP), 3. Relaxation period (RP)., , CONTRACTILITY, , 1. Isotonic Contraction, Isotonic contraction is the type of muscular contraction, in which the tension remains the same and the length, of the muscle fiber is altered (iso = same: tonic =, tension)., Example: Simple flexion of arm, where shortening of, muscle fibers occurs but the tension does not change., , 1. Latent period, Latent period is the time interval between the point of, stimulus and point of contraction. The muscle does not, show any mechanical activity during this period., , 2. Isometric Contraction, Isometric contraction is the type of muscular contraction, in which the length of muscle fibers remains the same, and the tension is increased., Example: Pulling any heavy object when muscles, become stiff and strained with increased tension but the, length does not change., SIMPLE MUSCLE CONTRACTION, OR TWITCH OR CURVE, The contractile property of the muscle is studied by, using gastrocnemius-sciatic preparation from frog. It is, also called muscle-nerve preparation., When the stimulus with threshold strength is applied,, the muscle contracts and then relaxes. These activities, are recorded graphically by using suitable instruments., The contraction is recorded as upward deflection from, the base line. And, relaxation is recorded as downward, deflection back to the base line (Fig. 30.2)., , FIGURE 30-2: Isotonic simple muscle curve, PS = Point of stimulus, PC = Point of contraction, PMC = Point of maximum contraction, PMR = Point of maximum relaxation, LP = Latent period (0.01 sec), CP = Contraction period (0.04 sec), RP = Relaxation period (0.05 sec)
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Chapter 30 t Properties of Skeletal Muscle 179, 2. Contraction period, Contraction period is the interval between point of, contraction and point of maximum contraction. Muscle, contracts during this period., 3. Relaxation period, Relaxation period is the interval between point of, maximum contraction and point of maximum relaxation., The muscle relaxes during this period., Duration of different periods in a typical simple, muscle curve:, Latent period, : 0.01 second, Contraction period : 0.04 second, Relaxation period : 0.05 second, Total twitch period : 0.10 second, Contraction period is always shorter than relaxation, period. It is because, the contraction is an active process, and relaxation is a passive process., , Similarly, depending upon contraction time and, myosin ATPase activity the muscle fibers are also, divided into two types:, 1. Type I fibers or slow fibers or slow twitch fibers,, which have small diameter., 2. Type II fibers or fast fibers or fast twitch fibers, which, have large diameter., Most of the skeletal muscles in human beings, contain both the types of fibers., Red Muscles, Muscles, which contain large quantity of myoglobin are, called red muscles. These muscles are also called slow, muscles or slow twitch muscles. Red muscles have, large number of type I fibers. The contraction time is, longer in this type of muscles., Example: Back muscles and gastrocnemius, muscles., Pale Muscles, , Causes of Latent Period, 1. Latent period is the time taken by the impulse to, travel along the nerve from place of stimulation to, muscle., 2. It is the time taken for the onset of initial chemical, changes in the muscle., 3. It is due to the delay in the conduction of impulse at, the neuromuscular junction., 4. It is due to the resistance offered by viscosity of the, muscle., 5. It is also due to the inertia of the recording instrument., Variations in Latent Period, Latent period is not constant. It varies even in, physiological conditions. It decreases in high temperature. It increases in low temperature, during fatigue, and with increase in weight., CONTRACTION TIME – RED MUSCLE, AND PALE MUSCLE, Contraction time or total twitch period varies from, species to species. It is less in homeothermic animals, than in poikilothermic animals. In the same animal, it, varies in different groups of muscles., Based on contraction time, the skeletal muscles are, classified into two types:, 1. Red muscles, 2. Pale muscles., , Muscles, which contain less quantity of myoglobin are, called pale muscles or white muscles. These muscles, are also called fast muscles or fast twitch muscles. Pale, muscles have large number of type II fibers. Contraction, time is shorter in this type of muscles., Examples: Hand muscles and ocular muscles., Characteristic features of red and pale muscles are, given in Table 30.1., FACTORS AFFECTING FORCE, OF CONTRACTION, Force of contraction of the skeletal muscle is affected by, the following factors:, 1. Strength of stimulus, 2. Number of stimulus, 3. Temperature, 4. Load., 1. Effect of Strength of Stimulus, When the muscle is stimulated by stimuli with different, strength (voltage of current), the force of contraction, also differs., Types of strength of stimulus, Strength of stimulus is of five types:, i. Subminimal or subliminal stimulus: It is less, than minimal strength and does not produce any, response in the muscle if applied once.
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180 Section 3 t Muscle Physiology, TABLE 30.1: Features of red and pale muscles, Red (slow) muscle, , Pale (fast) muscle, , 1., , Type I fibers are more, , Type II fibers are more, , 2., , Myoglobin content is high. So, it is red, , Myoglobin content is less. So, it is pale, , 3., , Sarcoplasmic reticulum is less extensive, , Sarcoplasmic reticulum is more extensive, , 4., , Blood vessels are more extensive, , Blood vessels are less extensive, , 5., , Mitochondria are more in number, , Mitochondria are less in number, , 6., , Response is slow with long latent period, , Response is rapid with short latent period, , 7., , Contraction is less powerful, , Contraction is more powerful, , 8., , This muscle is involved in prolonged and continued, activity as it undergoes sustained contraction, , This muscle is not involved in prolonged and continued, activity as it relaxes immediately, , 9., , Fatigue occurs slowly, , Fatigue occurs quickly, , Depends upon cellular respiration for ATP production, , Depends upon glycolysis for ATP production, , 10., , ii. Minimal stimulus, threshold stimulus or liminal, stimulus: It is the least strength of stimulus at which, minimum force of contraction is produced., iii. Submaximal stimulus: It is more than minimal and, less than maximal strength of stimulus. It produces, more force of contraction than minimal stimulus., iv. Maximal stimulus: It produces almost the maximum, force of contraction., v. Supramaximal stimulus: It produces the maximum, force of contraction. Beyond this, the force of, contraction cannot be increased., 2. Effect of Number of Stimulus, Contractility of the muscle varies, depending upon the, number of stimuli. If a single stimulus is applied, muscle, contracts once (simple muscle twitch). Two or more than, two (multiple) stimuli produce two different effects., Effects of two successive stimuli, When two stimuli are applied successively to a muscle,, three different effects are noticed depending upon the, interval between the two stimuli (Fig. 30.3):, i. Beneficial effect, ii. Superposition or wave summation, iii. Summation effect., i. Beneficial Effect, When two successive stimuli are applied to the muscle, in such a way that the second stimulus falls after the, relaxation period of the first curve, two separate curves, are obtained and the force of second contraction is, greater than that of first one. This is called beneficial, effect., , Cause for beneficial effect, During first contraction, the temperature increases., It decreases the viscosity of muscle. So, the force of, second contraction is more., ii. Superposition, While applying two successive stimuli, if the second, stimulus falls during relaxation period of first twitch,, two curves are obtained. However, the first curve is, superimposed by the second curve. This is called superposition or superimposition or incomplete summation., Here also, the second curve is bigger than the first curve, because of beneficial effect., iii. Summation, If second stimulus is applied during contraction period, or, during second half of latent period, the two contractions, are summed up and a single curve is obtained. This is, called summation curve or complete summation curve., Summation curve is different from the simple, muscle curve because, the amplitude of the summation, curve is greater than that of simple muscle curve. This is, due to the summation of two contractions to give rise to, one single curve. Base of the summation curve is also, broader than that of the simple muscle curve., Effects of multiple stimuli, In a muscle-nerve preparation, the multiple stimuli cause, two types of effects depending upon the frequency of, stimuli:, i. Fatigue, ii. Tetanus.
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Chapter 30 t Properties of Skeletal Muscle 181, i. Fatigue, Definition, Fatigue is defined as the decrease in muscular activity, due to repeated stimuli. When stimuli are applied, repeatedly, after some time, the muscle does not show, any response to the stimulus. This condition is called, fatigue., Fatigue curve, When the effect of repeated stimuli is recorded, continuously, the amplitude of first two or three, contractions increases. It is due to the beneficial effect., Afterwards, the force of contraction decreases gradually., It is shown by gradual decrease in the amplitude of, the curves. All the periods are gradually prolonged., Just before fatigue occurs, the muscle does not relax, completely. It remains in a partially contracted state. This, state is called contracture or contraction remainder, (Fig. 30.4)., Causes for fatigue, a. Exhaustion of acetylcholine in motor endplate, b. Accumulation of metabolites like lactic acid and, phosphoric acid, c. Lack of nutrients like glycogen, d. Lack of oxygen., , b. Anterior gray horn cells (motor neurons) of, spinal cord, c. Neuromuscular junction, d. Muscle., Recovery of the muscle after fatigue, Fatigue is a reversible phenomenon. Fatigued muscle, recovers (Fig. 30.5) if given rest and nutrition. For this,, the muscle is washed with saline., Causes of recovery, a. Removal of metabolites, b. Formation of acetylcholine at the neuromuscular, junction, c. Re-establishment of normal polarized state of, the muscle, d. Availability of nutrients, e. Availability of oxygen., The recovered muscle differs from the fresh resting, muscle by having acid reaction. The fresh resting muscle, is alkaline. But the muscle, recovered from fatigue is, acidic. So it relaxes slowly., In the intact body, all the processes involved, in recovery are achieved by circulation itself. In, human beings, fatigue is recorded by using Mosso’s, ergograph., , Site (seat) of fatigue, In the muscle-nerve preparation of frog, neuromuscular, junction is the first seat of fatigue. It is proved by direct, stimulation of fatigued muscle. Fatigued muscle gives, response if stimulated directly. However, the force of, contraction is less and the contraction is very slow., Second seat of fatigue is the muscle. And the nerve, cannot be fatigued., In the intact body, the sites of fatigue are in the, following order:, a. Betz (pyramidal) cells in cerebral cortex, , ii. Tetanus, Definition, Tetanus is defined as the sustained contraction of muscle, due to repeated stimuli with high frequency. When the, multiple stimuli are applied at a higher frequency in such, a way that the successive stimuli fall during contraction, period of previous twitch, the muscle remains in state of, tetanus. It relaxes only after the stoppage of stimulus or, when the muscle is fatigued., , FIGURE 30.3: Effects of two successive stimuli. PS1 = Point of first stimulus, PS2 = Point of second stimulus.
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182 Section 3 t Muscle Physiology, , FIGURE 30.4: Fatigue curve. PS = Point of stimulus., , FIGURE 30.5: Recovery curve. PS = Point of stimulus., , Tetanus and genesis of tetanus curves, Genesis of tetanus and tetanus in frog’s muscle is, recorded by using the instrument called vibrating, interruptor. It is used to adjust the frequency of stimuli, as 5, 10, 15, 20, 25, 30 and 35/second. While increasing, the frequency, fusion of contractions increases every, time and finally complete tetanus occurs (Fig. 30.6)., Nowadays, electronic stimulator is used. By using, this instrument, the stimuli with different strength and, frequency are obtained., When the frequency of stimuli is not sufficient to, cause tetanus, the fusion of contractions is not complete., It is called incomplete tetanus or clonus., Frequency of stimuli necessary to cause tetanus, and clonus, In frog gastrocnemius-sciatic preparation, the frequency, of stimuli required to cause tetanus is 40/second and for, clonus it is 35/second., , In gastrocnemius muscle of human being, the, frequency required to cause tetanus is 60/second. And, for clonus, the frequency of stimuli necessary is 55/, second., Pathological Tetanus, Sustained contraction of muscle due to repeated stimuli, of high frequency is usually called physiological tetanus., It is distinct from pathological tetanus, which refers to, the spastic contraction of the different muscle groups, in pathological conditions. This disease is caused by, bacillus Clostridium tetani found in the soil, dust and, manure. The bacillus enters the body through a cut,, wound or puncture caused by objects like metal pieces,, metal nails, pins, wood splinters, etc., This disease affects the nervous system and its, common features are muscle spasm and paralysis., The first appearing symptom is the spasm of the jaw
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Chapter 30 t Properties of Skeletal Muscle 183, muscles resulting in locking of jaw. Therefore, tetanus, is also called lockjaw disease. The manifestations of, tetanus are due to a toxin secreted by the bacteria. If, timely treatment is not provided, the condition becomes, serious and it may even lead to death., Treppe or Staircase Phenomenon, Treppe or staircase phenomenon is the gradual increase, in force of contraction of muscle when it is stimulated, repeatedly with a maximal strength at a low frequency., It is due to beneficial effect. Treppe is distinct from, summation of contractions and tetanus., , i. Excitability of muscle decreases, ii. Chemical processes are slowed or delayed, iii. Viscosity of the muscle increases., High or hot temperature – Heat rigor, At high temperature above 60°C, the muscle develops heat, rigor. Rigor refers to shortening and stiffening of muscle, fibers. Heat rigor is the rigor that occurs due to increased, temperature. It is an irreversible phenomenon., Cause of heat rigor is the coagulation of muscle, proteins, actin and myosin., Other types of rigors, , 3. Effect of Variations in Temperature, If the temperature of muscle is altered, the force of, contraction is also affected (Fig. 30.7)., Warm temperature, At warm temperature of about 40°C, the force of muscle, contraction increases and all the periods are shortened, because of the following reasons:, i. Excitability of muscle increases, ii. Chemical processes involved in muscular, contraction are accelerated, iii. Viscosity of muscle decreases., Cold temperature, At cold temperature of about 10°C, the force of contraction decreases and all the periods are prolonged, because of the following reasons:, , i. Cold rigor: Due to the exposure to severe cold., It is a reversible phenomenon., ii. Calcium rigor: Due to increased calcium content., It is also reversible., iii. Rigor mortis: Develops after death., Rigor mortis, Rigor mortis refers to a condition of the body after death,, which is characterized by stiffness of muscles and joints, (Latin word ‘rigor’ means stiff). It occurs due to stoppage, of aerobic respiration, which causes changes in the, muscles., Cause of rigor mortis, Soon after death, the cell membrane becomes highly, permeable to calcium. So a large number of calcium ions, , FIGURE 30.6: Genesis of tetanus and tetanus curves
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184 Section 3 t Muscle Physiology, 4. Effect of Load, Load acting on muscle is of two types:, i. After load, ii. Free load., After load, After load is the load, that acts on the muscle after the, beginning of muscular contraction. Example of after load, is lifting any object from the ground. The load acts on, muscles of arm only after lifting the object off the ground,, i.e. only after beginning of the muscular contraction., Free load, FIGURE 30.7: Effects of variations of temperature, , enters the muscle fibers and promotes the formation, of actomyosin complex resulting in contraction of the, muscles., Few hours after death, all the muscles of body, undergo severe contraction and become rigid. The, joints also become stiff and locked., Normally for relaxation, the muscle needs to drive out, the calcium, which requires ATP. But during continuous, muscular contraction and other cellular processes after, death, the ATP molecules are completely exhausted., New ATP molecules cannot be produced because of lack, of oxygen. So in the absence of ATP, the muscles remain, in contracted state until the onset of decomposition., Medicolegal importance of rigor mortis, Rigor mortis is useful in determining the time of death., Onset of stiffness starts between 10 minutes and 3, hours after death depending upon condition of the body, and environmental temperature at the time of death. If, the body is active or the environmental temperature is, high at the time of death, the stiffness sets in quickly., The stiffness develops first in facial muscles and, then spreads to other muscles. The maximum stiffness, occurs around 12 to 24 hours after death. The stiffness, of muscles and joints continues for 1 to 3 days., Afterwards, the decomposition of the general, tissues starts. Now the lysosomal intracellular hydrolytic, enzymes like cathepsins and calpains are released., These enzymes hydrolyze the muscle proteins, actin, and myosin resulting in breakdown of actomyosin, complex. It relieves the stiffness of the muscles. This, process is known as resolution of rigor., , Free load is the load, which acts on the muscle freely,, even before the onset of contraction of the muscle. It is, otherwise called fore load. Example of free load is filling, water from a tap by holding the bucket in hand., Free load Vs after load, Free load is more beneficial (advantageous) since force, of contraction and work done by the muscles are greater, in free-loaded condition than in after-loaded condition. It, is because, in free-loaded condition, the muscle fibers, are stretched and the initial length of muscle fibers is, increased. It facilitates the force of contraction. This is, in accordance with Frank-Starling law., Frank-Starling law, Frank-Starling law states that the force of contraction is, directly proportional to the initial length of muscle fibers, within physiological limits., Experiment to prove Frank-Starling law, Frank-Starling law can be proved by using the musclenerve preparation of frog. First, one simple muscle curve, is recorded with 10 g weight in after-loaded condition, of the muscle (Fig. 30.8). Then, many contractions are, recorded by increasing the weight everytime, until the, muscle fails to lift the weight or till the curve becomes, almost flat near the base line. The work done by the, muscle is calculated for every weight (Fig. 30.9)., Effects of increasing the weight in after-loaded, condition are:, i. Force of contraction decreases gradually, ii. Latent period prolongs, iii. Contraction and relaxation periods shorten (Fig., 30.8)., Afterwards, the muscle (with weight added for last, contraction) in after-loaded condition, is brought to the, free-loaded condition and stimulated. Now, the muscle
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Chapter 30 t Properties of Skeletal Muscle 185, contracts and a curve is recorded. The work done by the, muscle is calculated., Work done in free-loaded condition is more than in, after-loaded condition. This proves Frank-Starling law,, i.e. the force of contraction is directly proportional to the, initial length of muscle fiber., Work done by the muscle, Work done is calculated by the formula:, Work done = W × h, Where, W = Weight lifted by the muscle, h = Height up to which the weight is lifted, ‘h’ is determined by the formula, l×H, h =, L, This formula is derived as follows:, Δ ABC, =, Δ DEC, BC, AB, L, =, or, EC, DE, l, h×L =, h, L, l, H, h, , =, , =, , H, h, , l×H, l×H, L, , = Length between fulcrum and writing point, = Length between fulcrum and point where weight, is added, = Height of the curve, = Height up to which the weight is lifted, So work done by the muscle =, l×H, W×, g cm, L, Work done is expressed as ergs or g cm., , Optimum load, Optimum load is the load at which the work done by the, muscle is maximum., LENGTH-TENSION RELATIONSHIP, Tension or force developed in the muscle during resting, condition and during contraction varies with the length, of the muscle., Tension developed in the muscle during resting, condition is known as passive tension. Tension, developed in the muscle during isometric contraction is, called total tension., , FIGURE 30.8: Effect of after load and free load. PS = Point of, stimulus. In free-loaded condition, the force of contraction is, greater than in after-loaded condition with the same weight., , Active Tension, Difference between the passive tension and total, tension at a particular length of the muscle is called, active tension. Active tension is considered as the real, tension that is generated in the muscle during contractile, process. It can be determined by the length-tension, curve., Length-Tension Curve, Length-tension curve is the curve that determines, the relationship between length of muscle fibers and, the tension developed by the muscle. It is also called, length-force curve. The curve is obtained by using frog, gastrocnemius-sciatic preparation. Muscle is attached, to micrometer on one end and to a force transducer on, other end. Muscle is not allowed to shorten because of, its attachment on both the ends (Fig. 30.10)., A micrometer is used to set length of the muscle, fibers. Force transducer is connected to a polygraph., Polygraph is used to measure the tension developed by, the muscle during isometric contraction.
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186 Section 3 t Muscle Physiology, tension gradually increases up to the resting length., During stretching of the muscle beyond resting length,, there is reduction in the overlap between the actin and, myosin filaments and the number of cross bridges., And the active tension starts declining beyond resting, length., REFRACTORY PERIOD, , FIGURE 30.9: Work done by the muscle, L = Length between fulcrum and writing point, l = Length between fulcrum and point where weight is, added, H = Height of the curve, h = Height up to which the weight is lifted, W = Weight, , To begin with, the minimum length of the muscle, is set by using the micrometer. The passive tension is, determined by using force transducer. Then the muscle, is stimulated and total tension is determined. From these, two values the active tension is calculated. Then the, length of muscle is increased gradually. At every length,, both passive tension and total tension are determined, followed by calculation of active tension. All the values, of active tension at different lengths are plotted to obtain, the length-tension curve (Fig. 30.11). From the curve the, resting length is determined., , Refractory period is the period at which the muscle, does not show any response to a stimulus. It is because, already one action potential is in progress in the muscle, during this period. The muscle is unexcitable to further, stimulation until it is repolarized., Refractory period is of two types., 1. Absolute refractory period, 2. Relative refractory period, 1. Absolute Refractory Period, Absolute refractory period is the period during which the, muscle does not show any response at all, whatever, may be the strength of stimulus., , Resting Length, Resting length is the length of the muscle at which the, active tension is maximum. Active tension is proportional, to the length of the muscle up to resting length. Beyond, resting length, the active tension decreases., Tension Vs Overlap of Myofilaments, Length-tension relationship is explained on the basis of, sliding of actin filaments over the myosin filaments during, muscular contraction. The active tension is proportional, to overlap between actin and myosin filaments in the, sarcomere and the number of cross bridges formed, between actin and myosin filaments. When the length, of the muscle is less than the resting length, there is, increase in the overlap between the actin and myosin, filaments and the number of cross bridges. The active, , FIGURE 30.10: Experimental setup to measure the tension, developed in the muscle
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Chapter 30 t Properties of Skeletal Muscle 187, Significance of long refractory period in cardiac muscle, Because of the long refractory period, cardiac muscle, does not show:, i. Complete summation of contractions, ii. Fatigue, iii. Tetanus., , MUSCLE TONE, DEFINITION, Muscle tone is defined as continuous and partial, contraction of the muscles with certain degree of vigor, and tension. More details on muscle tone are given in, Chapter 157., MAINTENANCE OF MUSCLE TONE, In Skeletal Muscle, FIGURE 30.11: Length-tension curve, , 2. Relative Refractory Period, Relative refractory period is the period, during which the, muscle shows some response if the strength of stimulus, is increased to maximum., Refractory Period in Skeletal Muscle, In skeletal muscle, whole of the latent period is refractory, period. The absolute refractory period falls during first, half of latent period (0.005 sec). And, relative refractory, period extends during second half of latent period (0.005, sec). Totally, it is 0.01 sec., Refractory Period in Cardiac Muscle, In cardiac muscle, absolute refractory period extends, throughout contraction period (0.27 sec). And, relative, refractory period extends during first half of relaxation, period (about 0.26 sec). Totally it is about 0.53 sec., Thus, the refractory period in cardiac muscle is very, long compared to that of skeletal muscle., , Maintenance of tone in skeletal muscle is neurogenic. It, is due to continuous discharge of impulses from gamma, motor neurons in anterior gray horn of spinal cord. The, gamma motor neurons in spinal cord are controlled by, higher centers in brain (Chapter 157)., In Cardiac Muscle, In cardiac muscle, maintenance of tone is purely, myogenic, i.e. the muscles themselves control the, tone. The tone is not under nervous control in cardiac, muscle., In Smooth Muscle, In smooth muscle, tone is myogenic. It depends upon, calcium level and number of cross bridges., APPLIED PHYSIOLOGY – ABNORMALITIES, OF MUSCLE TONE, Abnormalities of muscle tone are:, 1. Hypertonia, 2. Hypotonia, 3. Myotonia., Refer Chapter 34 for details.
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Changes during, Muscular Contraction, , Chapter, , 31, , INTRODUCTION, ELECTRICAL CHANGES, , , , , , , , RESTING MEMBRANE POTENTIAL, ACTION POTENTIAL, ACTION POTENTIAL CURVE, MONOPHASIC, BIPHASIC AND COMPOUND ACTION POTENTIALS, GRADED POTENTIAL, PATCH-CLAMP TECHNIQUE, , PHYSICAL CHANGES, HISTOLOGICAL CHANGES, , , , ACTOMYOSIN COMPLEX, MOLECULAR BASIS OF CONTRACTION, , CHEMICAL CHANGES, , , LIBERATION OF ENERGY, CHANGES IN pH, , THERMAL CHANGES, , , , , RESTING HEAT, INITIAL HEAT, RECOVERY HEAT, , INTRODUCTION, The muscle contracts when it is stimulated. Contraction, of the muscle is a physical or mechanical event. In addi, tion, several other changes occur in the muscle., Changes taking place during muscular contraction:, 1. Electrical changes, 2. Physical changes, 3. Histological (molecular) changes, 4. Chemical changes, 5. Thermal changes., , ELECTRICAL CHANGES DURING, MUSCULAR CONTRACTION, Electrical events occur in the muscle during resting, condition as well as active conditions. Electrical potential, , in the muscle during resting condition is called resting, membrane potential., Electrical changes that occur in active conditions,, i.e. when the muscle is stimulated are together called, action potential., Electrical potentials in a muscle (or any living tissue), are measured by using a cathode ray oscilloscope or, computerized polygraph., RESTING MEMBRANE POTENTIAL, Resting membrane potential is defined as the electrical, potential difference (voltage) across the cell membrane, (between inside and outside of the cell) under resting, condition., It is also called membrane potential, transmembrane, potential, transmembrane potential difference or trans, membrane potential gradient.
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Chapter 31 t Changes during Muscular Contraction 189, When two electrodes are connected to a cathode, ray oscilloscope through a suitable amplifier and placed, over the surface of the muscle fiber, there is no potential, difference, i.e. there is zero potential difference. But,, if one of the electrodes is inserted into the interior of, muscle fiber, potential difference is observed across the, sarcolemma (cell membrane). There is negativity inside, and positivity outside the muscle fiber. This potential, difference is constant and is called resting membrane, potential. The condition of the muscle during resting mem, brane potential is called polarized state. In human, skeletal muscle, the resting membrane potential is, –90 mV., Ionic Basis of Resting Membrane Potential, Development and maintenance of resting membrane, potential in a muscle fiber or a neuron are carried out by, movement of ions, which produce ionic imbalance across, the cell membrane. This results in the development of, more positivity outside and more negativity inside the cell., Ionic imbalance is produced by two factors:, 1. Sodiumpotassium pump, 2. Selective permeability of cell membrane., 1. Sodium-potassium pump, Sodium and potassium ions are actively transported in, opposite directions across the cell membrane by means, of an electrogenic pump called sodiumpotassium, pump. It moves three sodium ions out of the cell and, two potassium ions inside the cell by using energy from, ATP. Since more positive ions (cations) are pumped, outside than inside, a net deficit of positive ions occurs, inside the cell. It leads to negativity inside and positivity, outside the cell (Fig. 31.1). More details of this pump are, given in Chapter 3., 2. Selective permeability of cell membrane, Permeability of cell membrane depends largely on the, transport channels. The transport channels are selec, tive for the movement of some specific ions. Their, permeability to these ions also varies. Most of the chan, nels are gated channels and the specific ions can move, across the membrane only when these gated channels, are opened., Two types of channels are involved:, i. Channels for major anions like proteins, ii. Leak channels., i. Channels for major anions (negatively charged, substances) like proteins, Channels for some of the negatively charged large subs, tances such as proteins, organic phosphate and sulfate, compounds are absent or closed. So, such substances, remain inside the cell and play a major role in the, , development and maintenance of negativity inside the, cell (resting membrane potential)., ii. Leak channels, Leak channels are the passive channels, which maintain, the resting membrane potential by allowing movement, of positive ions (Na+ and K+) across the cell membrane., Three important ions, sodium, chloride and, potassium are unequally distributed across the cell, membrane. Na+ and Cl– are more outside and K+ is, more inside., Since, Cl– channels are mostly closed in resting, conditions Cl– are retained outside the cell. Thus, only, the positive ions, Na+ and K+ can move across the cell, membrane., Na+ is actively transported (against the concentration, gradient) out of cell and K+ is actively transported (against, the concentration gradient) into the cell. However,, because of concentration gradient, Na+ diffuses back, into the cell through Na+ leak channels and K+ diffuses, out of the cell through K+ leak channels., In resting conditions, almost all the K+ leak, channels are opened but most of the Na+ leak channels, are closed. Because of this, K+, which are transported, actively into the cell, can diffuse back out of the cell in, an attempt to maintain the concentration equilibrium., But among the Na+, which are transported actively out, of the cell, only a small amount can diffuse back into, the cell. That means, in resting conditions, the passive, K+ efflux is much greater than the passive Na+ influx., It helps in establishing and maintaining the resting, membrane potential., After establishment of the resting membrane, potential (i.e. inside negativity and outside positivity),, the efflux of K+ stops in spite of concentration gradient., It is because of two reasons:, i. Positivity outside the cell repels positive K+ and, prevents further efflux of these ions, ii. Negativity inside the cell attracts positive K+ and, prevents further leakage of these ions outside., Importance of intracellular potassium ions, Concentration of K+ inside the cell is about 140 mEq/L. It, is almost equal to that of Na+ outside. The high concen, tration of K+ inside the cell is essential to check the, negativity. Normally, the negativity (resting membrane, potential) inside the muscle fiber is –90 mV and in a, nerve fiber, it is –70 mV. It is because of the presence, of negatively charged proteins, organic phosphates and, sulfates, which cannot move out normally. Suppose if the, K+ is not present or decreased, the negativity increases
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190 Section 3 t Muscle Physiology, , FIGURE 31.1: Development of resting membrane potential by sodiumpotassium (Na+K+) pump and diffusion of ions. Na+K+, pump actively pumps three Na+ outside and two K+ into the cell. However, the diffusion of K+ out of the cell is many times greater, than the diffusion of Na+ inside the cell because many of the K+ leak channels are opened and many of the Na+ leak channels, are closed., , beyond –120 mV, which is called hyperpolarization. At, this stage, the development of action potential is either, delayed or does not occur., , ACTION POTENTIAL CURVE, , Action potential is defined as a series of electrical, changes that occur in the membrane potential when the, muscle or nerve is stimulated., Action potential occurs in two phases:, 1. Depolarization, 2. Repolarization., , Action potential curve is the graphical registration of, electrical activity that occurs in an excitable tissue, such as muscle after stimulation. It shows three major, parts:, 1. Latent period, 2. Depolarization, 3. Repolarization., Resting membrane potential in skeletal muscle is, –90 mV and it is recorded as a straight baseline (Fig., 31.2)., , Depolarization, , 1. Latent Period, , Depolarization is the initial phase of action potential, in which inside of the muscle becomes positive and, outside becomes negative. That is, the polarized state, (resting membrane potential) is abolished resulting in, depolarization., , Latent period is the period when no change occurs in, the electrical potential immediately after applying the, stimulus. It is a very short period with duration of 0.5 to, 1 millisecond., , Repolarization, , When a stimulus is applied, there is a slight irregular, deflection of baseline for a very short period. This is, called stimulus artifact. The artifact occurs because of, the disturbance in the muscle due to leakage of current, from stimulating electrode to the recording electrode., The stimulus artifact is followed by latent period., , ACTION POTENTIAL, , Repolarization is the phase of action potential in which, the muscle reverses back to the resting membrane, potential. That is, within a short time after depolarization, the inside of muscle becomes negative and outside, becomes positive. So, the polarized state of the muscle, is reestablished., Properties of Action Potential, Properties of action potential are listed in Table 31.1., , Stimulus artifact, , 2. Depolarization, Depolarization starts after the latent period. Initially, it is, very slow and the muscle is depolarized for about 15 mV.
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Chapter 31 t Changes during Muscular Contraction 191, Firing level and depolarization, After the initial slow depolarization for 15 mV (up to –75, mV), the rate of depolarization increases suddenly. The, point at which, the depolarization increases suddenly is, called firing level., , Unlike the Na+ channels, the K+ channels remain, open for longer duration. These channels remain, opened for few more milliseconds after completion of, repolarization. It causes efflux of more number of K+, producing more negativity inside. It is the cause for, hyperpolarization., , Overshoot, From firing level, the curve reaches isoelectric potential, (zero potential) rapidly and then shoots up (overshoots), beyond the zero potential (isoelectric base) up to +55, mV. It is called overshoot., 3. Repolarization, When depolarization is completed (+55 mV), the, repolarization starts. Initially, the repolarization occurs, rapidly and then it becomes slow., Spike potential, Rapid rise in depolarization and the rapid fall in, repolarization are together called spike potential. It lasts, for 0.4 millisecond., After depolarization or negative after potential, Rapid fall in repolarization is followed by a slow re, polarization. It is called after depolarization or negative, after potential. Its duration is 2 to 4 milliseconds., After hyperpolarization or positive after potential, After reaching the resting level (–90 mV), it becomes, more negative beyond resting level. This is called after, hyperpolarization or positive after potential. This lasts, for more than 50 milliseconds. After this, the normal, resting membrane potential is restored slowly., Ionic Basis of Action Potential, Voltage gated Na+ channels and the voltage gated K+, channels play important role in the development of, action potential., During the onset of depolarization, voltage gated, sodium channels open and there is slow influx of Na+., When depolarization reaches 7 to 10 mV, the voltage, gated Na+ channels start opening at a faster rate. It is, called Na+ channel activation. When the firing level is, reached, the influx of Na+ is very great and it leads to, overshoot., But the Na+ transport is short lived. It is because, of rapid inactivation of Na+ channels. Thus, the Na+, channels open and close quickly. At the same time, the, K+ channels start opening. This leads to efflux of K+ out, of the cell, causing repolarization., , FIGURE 31.2: Action potential in a skeletal muscle, A = Opening of few Na+ channels, B = Opening of many Na+ channels, C = Closure of Na+ channels and opening, of K+ channels, D = Closure of K+ channels
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192 Section 3 t Muscle Physiology, MONOPHASIC, BIPHASIC AND COMPOUND, ACTION POTENTIALS, Monophasic Action Potential, Monophasic action potential is the series of electrical, changes that occur in a stimulated muscle or nerve, fiber, which is recorded by placing one electrode on its, surface and the other inside. It is characterized by a, positive deflection. The action potential in the muscle, discussed above belongs to this category., Biphasic Action Potential, , electrodes becomes zero and the graph shows the, baseline (Fig. 31.3E). Since this recording shows, both positive and negative components it is called, biphasic action potential., Effect of crushing or local anesthetics, When a small portion of axon between the two electrodes, is affected by crushing or local anesthetics, the action, potential cannot travel through this part of the axon. So,, while recording the potential only a single deflection, (monophasic) action potential is recorded (Fig. 31.4)., , Biphasic or diphasic action potential is the series of, electrical changes in a stimulated muscle or nerve, fiber, which is recorded by placing both the recording, electrodes on the surface of the muscle or nerve fiber. It, is characterized by a positive deflection followed by an, isoelectric pause and a negative deflection., Recording of biphasic action potential, Biphasic action potential is recorded by extracellular, electrodes, i.e. by placing both the recording electrodes, on the surface of a nerve fiber or muscle. Figure 31.3, explains the biphasic action potential in an axon., Sequence of events of biphasic action potential:, 1. In resting state before stimulation, the potential, difference between the two electrodes is zero. So, the recording shows a baseline (Fig. 31.3A)., 2. When the axon is stimulated at one end, the action, potential (impulse) is generated and it travels, towards the other end of an axon by passing, through the recording electrodes. When the impulse, reaches first electrode, the membrane under this, electrode becomes depolarized (outside negative), but the membrane under second electrode is still, in polarized state (outside positive). By convention,, this is graphically recorded as an upward deflection, (Fig. 31.3B)., 3. When the impulse crosses and travels away from the, first electrode, the membrane under this electrode, is repolarized. Later when the impulse just travels, in between the two electrodes (before reaching the, second electrode) the potential difference between, both the electrode falls to zero and the baseline is, recorded (Fig. 31.3C), 4. When the impulse reaches the second electrode,, the membrane under this electrode is depolarized, (outside negative) and a negative deflection is, recorded (Fig. 31.3D)., 5. When the impulse travels away from second, electrode, the membrane under this gets repolarized., Once again the potential difference between the two, , FIGURE 31.3: Biphasic action potential in an axon recorded, by placing both the electrodes outside the axon, A = Resting state – zero potential, B = Depolarization of membrane under first electrode, C = Repolarization of membrane under first electrode, followed by zero potential, D = Depolarization of membrane under second electrode, E = Repolarization of membrane under second electrode
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Chapter 31 t Changes during Muscular Contraction 193, TABLE 31.1: Properties of action potential, and graded potential, Action Potential, , FIGURE 31.4: Monophasic action potential in a crushed axon, , Graded potential, , Propagative, , Nonpropagative, , Longdistance signal, , Shortdistance signal, , Both depolarization and, repolarization, , Only depolarization or, hyperpolarization, , Obeys allornone law, , Does not obey allornone law, , Summation is not possible Summation is possible, , Compound Action Potential, Compound action potential (CAP) is the algebraic, summation of all the action potentials produced by all, the nerve fibers. Each nerve is made up of thousands of, axons. While stimulating the whole nerve, all the nerve, fibers are activated and produce action potential. The, compound action potential is obtained by recording all, the action potentials simultaneously., GRADED POTENTIAL, Graded potential is a mild local change in the membrane, potential that develops in receptors, synapse or neuro, muscular junction when stimulated. It is also called, graded membrane potential, graded depolarization or, local potential. It is nonpropagative and characterized by, mild depolarization or hyperpolarization. Graded poten, tial is distinct from the action potential and the properties, of these two potentials are given in table 31.1., In most of the cases, the graded potential is, responsible for the generation of action potential. How, ever, in some cases the graded potential hyperpolarizes, the membrane potential (more negativity than resting, membrane potential) and inhibits the generation of action, potential (as in inhibitory synapses: Chapter 140)., Different Graded potentials, 1. End plate potential in neuromuscular junction, (Chapter 32), 2. Electronic potential in nerve fibers (Chapter 136), 3. Receptor potential (Chapter 139), 4. Excitatory postsynaptic potential (Chapter 140), 5. Inhibitory postsynaptic potential (Chapter 140)., PATCH-CLAMP TECHNIQUE, Patchclamp technique or patch clamping is the method, to measure the ion currents across the biological, membranes. This advanced technique in modern, electrophysiology was established by Erwin Neher, in 1992. Patch clamp is modified as voltage clamp to, , Has refractory period, , No refractory period, , study the ion currents across the membrane of neuron, (Chapter 136)., Procedure, Patch-clamp experiments use mostly the cultured cells., The cells isolated from the body are placed in dishes, containing culture media and kept in an incubator., Probing a single cell, The dish with tissue culture cells is mounted on a, microscope. A micropipette with an opening of about, 0.5 µ is also mounted by means of a pipette holder. The, pipette is filled with saline solution. An electrode is fitted, to the pipette and connected to a recording device called, patch-clamp amplifier. The micropipette is pressed firmly, against the membrane of an intact cell. A gentle suction, applied to the inside of the pipette forms a tight seal of, giga ohms (GΩ) resistance between the membrane and, the pipette., This patch (minute part) of the cell membrane under, the pipette is studied by means of various approaches, called patch-clamp configurations (Fig. 31.5)., Patch-clamp Configurations, 1. Cell-attached patch, The cell is left intact with its membrane. This allows, measurement of current flow through ion channel or, channels under the micropipette (Fig. 31.5 A)., 2. Inside-out patch, From the cell-attached configuration, the pipette is gently, pulled away from the cell. It causes the detachment of, a small portion of membrane from the cell. The external, surface of the membrane patch faces pipette solution., But internal surface of the membrane patch is exposed, out hence the name insideout patch (Fig. 31.5 B)., Pipette with membrane patch is inserted into a, container with free solution. Concentration of ions can
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194 Section 3 t Muscle Physiology, also helps to study the effects of neurotransmitters and, compounds like ozone, Gprotein regulators, etc. on the, ion channels., , PHYSICAL CHANGES DURING, MUSCULAR CONTRACTION, Physical change, which takes place during muscular, contraction, is the change in length of the muscle fibers or, change in tension developed in the muscle. Depending, upon this, the muscular contraction is classified into, two types namely isotonic contraction and isometric, contraction (refer previous chapter)., , HISTOLOGICAL CHANGES DURING, MUSCULAR CONTRACTION, ACTOMYOSIN COMPLEX, In relaxed state of the muscle, the thin actin filaments, from opposite ends of sarcomere are away from each, other leaving a broad ‘H’ zone., During contraction of the muscle, actin (thin), filaments glide over myosin (thick) filaments and form, actomyosin complex., FIGURE 31.5: Patch-clamp configurations, , be altered in the free solution. It is used to study the, effect of alterations in the ion concentrations on the ion, channels., 3. Whole-cell patch, From the cell-attached configuration, further suction is, applied to the inside of the pipette. It causes rupture, of the membrane and the pipette solution starts mixing, with intracellular fluid. When the mixing is complete, the, equilibrium is obtained between the pipette solution and, the intracellular fluid (Fig. 31.5 C)., Whole-cell patch is used to record the current flow, through all the ion channels in the cell. The cellular, activity also can be studied directly., 4. Outside-out patch, From the whole-cell configuration the pipette is gently, pulled away from the cell. A portion of membrane is torn, away from the cell. Immediately, the free ends of the, torn membrane fuse and reseal forming a membrane, vesicle at tip of the pipette. The pipette solution enters, the membrane vesicle and forms the intracellular fluid., The vesicle is placed inside a bath solution, which forms, the extracellular environment (Fig. 31.5D)., This patch is used to study the effect of changes, in the extracellular environment on the ion channels. It, , MOLECULAR BASIS OF, MUSCULAR CONTRACTION, Molecular mechanism is responsible for formation of, actomyosin complex that results in muscular contraction., It includes three stages:, 1. Excitation-contraction coupling., 2. Role of troponin and tropomyosin., 3. Sliding mechanism., 1. Excitation-contraction Coupling, Excitation-contraction coupling is the process that, occurs in between the excitation and contraction of the, muscle. This process involves series of activities, which, are responsible for the contraction of excited muscle., Stages of excitation-contraction coupling, When a muscle is excited (stimulated) by the impulses, passing through motor nerve and neuromuscular junc, tion, action potential is generated in the muscle fiber., Action potential spreads over sarcolemma and also, into the muscle fiber through the ‘T’ tubules. The ‘T’, tubules are responsible for the rapid spread of action, potential into the muscle fiber. When the action potential, reaches the cisternae of ‘L’ tubules, these cisternae are, excited. Now, the calcium ions stored in the cisternae, are released into the sarcoplasm (Fig. 31.6). The calcium ions from the sarcoplasm move towards the actin, filaments to produce the contraction.
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Chapter 31 t Changes during Muscular Contraction 195, 2. Role of Troponin and Tropomyosin, Normally, the head of myosin molecules has a strong, tendency to get attached with active site of F actin., However, in relaxed condition, the active site of F actin, is covered by the tropomyosin. Therefore, the myosin, head cannot combine with actin molecule., Large number of calcium ions, which are released, from ‘L’ tubules during the excitation of the muscle, bind, with troponin C. The loading of troponin C with calcium, ions produces some change in the position of troponin, molecule. It in turn, pulls tropomyosin molecule away from, F actin. Due to the movement of tropomyosin, the active, site of F actin is uncovered and exposed. Immediately, the head of myosin gets attached to the actin., 3. Sliding Mechanism and Formation of, Actomyosin Complex – Sliding Theory, , FIGURE 31.6: Excitation-contraction coupling, , Thus, the calcium ion forms the link or coupling, material between the excitation and the contraction of, muscle. Hence, the calcium ions are said to form the, basis of excitation-contraction coupling., , Sliding theory explains how the actin filaments slide, over myosin filaments and form the actomyosin complex, during muscular contraction. It is also called ratchet, theory or walk along theory., Each cross bridge from the myosin filaments has, got three components namely, a hinge, an arm and a, head., After binding with active site of F actin, the myosin, head is tilted towards the arm so that the actin filament, is dragged along with it (Fig. 31.7). This tilting of head is, called power stroke. After tilting, the head immediately, breaks away from the active site and returns to the, original position. Now, it combines with a new active, site on the actin molecule. And, tilting movement occurs, again. Thus, the head of cross bridge bends back and, forth and pulls the actin filament towards the center of, sarcomere. In this way, all the actin filaments of both the, ends of sarcomere are pulled. So, the actin filaments of, , FIGURE 31.7: Diagram showing power stroke by myosin head., Stage 1: Myosin head binds with actin; Stage 2: Tilting of myosin head (power stroke) drags the actin filament.
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196 Section 3 t Muscle Physiology, opposite sides overlap and form actomyosin complex., Formation of actomyosin complex results in contraction, of the muscle., When the muscle shortens further, the actin, filaments from opposite ends of the sarcomere approach, each other. So, the ‘H’ zone becomes narrow. And, the, two ‘Z’ lines come closer with reduction in length of, the sarcomere. However, the length of ‘A’ band is not, altered. But, the length of ‘I’ band decreases., When the muscular contraction becomes severe,, the actin filaments from opposite ends overlap and the, ‘H’ zone disappears., Changes in sarcomere during muscular contraction, Thus, changes that take place in sarcomere during, muscular contraction are:, 1. Length of all the sarcomeres decreases as the ‘Z’, lines come close to each other, 2. Length of the ‘I’ band decreases since the actin, filaments from opposite side overlap, 3. ‘H’ zone either decreases or disappears, 4. Length of ‘A’ band remains the same., Summary of sequence of events during muscular, contraction is given in Figure 31.8., Energy for Muscular Contraction, Energy for movement of myosin head (power stroke), is obtained by breakdown of adenosine triphosphate, (ATP) into adenosine diphosphate (ADP) and inorganic, phosphate (Pi)., Head of myosin has a site for ATP. Actually the head, itself can act as the enzyme ATPase and catalyze the, breakdown of ATP. Even before the onset of contraction,, an ATP molecule binds with myosin head., When tropomyosin moves to expose the active, sites, the head is attached to the active site. Now, ATPase cleaves ATP into ADP and Pi, which remains in, head itself. The energy released during this process is, utilized for contraction., When head is tilted, the ADP and Pi are released, and a new ATP molecule binds with head. This process, is repeated until the muscular contraction is completed., Relaxation of the Muscle, , FIGURE 31.8: Sliding mechanism, , Relaxation of the muscle occurs when the calcium ions, are pumped back into the L tubules. When calcium, ions enter the L tubules, calcium content in sarcoplasm, decreases leading to the release of calcium ions from, the troponin. It causes detachment of myosin from, actin followed by relaxation of the muscle (Fig. 31.9)., The detachment of myosin from actin obtains energy, from breakdown of ATP. Thus, the chemical process of
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Chapter 31 t Changes during Muscular Contraction 197, Energy liberated during ATP breakdown is sufficient, for maintaining full contraction of the muscle for a short, duration of less than one second., Resynthesis of ATP, Adenosine diphosphate, which is formed during ATP, breakdown, is immediately utilized for the resynthesis, of ATP. But, for the resynthesis of ATP, the ADP cannot, combine with Pi. It should combine with a highenergy, phosphate radical. There are two sources from which, the highenergy phosphate is obtained namely, creatine, phosphate and carbohydrate metabolism., Resynthesis of ATP from creatine phosphate, , FIGURE 31.9: Sequence of events during, muscular relaxation, , muscular relaxation is an active process although the, physical process is said to be passive., Molecular Motors, Along with other proteins and some enzymes, actin and, myosin form the molecular motors, which are involved, in movements. Refer Chapter 3 for details., , CHEMICAL CHANGES DURING, MUSCULAR CONTRACTION, LIBERATION OF ENERGY, Energy necessary for muscular contraction is liberated, during the processes of breakdown and resynthesis of, ATP., Breakdown of ATP, During muscular contraction, the supply of energy is, from the breakdown of ATP. This is broken into ADP and, inorganic phosphate (Pi) and energy is liberated., ATP → ADP + Pi, ↓, Energy, Energy liberated by breakdown of ATP is responsible, for the following activities during muscular contraction:, 1. Spread of action potential into the muscle, 2. Liberation of calcium ions from cisternae of ‘L’, tubules into the sarcoplasm, 3. Movements of myosin head, 4. Sliding mechanism., , Immediate supply of high-energy phosphate radical, is from the creatine phosphate (CP). Plenty of CP, is available in resting muscle. In the presence of the, enzyme creatine phosphotransferase, highenergy, phosphate is released from creatine phosphate. The, reaction is called Lohmann’s reaction., ADP + CP → ATP + Creatine, Energy produced in this reaction is sufficient to, maintain muscular contraction only for few seconds., Creatine should be resynthesized into creatine phos, phate and this requires the presence of highenergy, phosphate. So, the required amount of highenergy, phosphate radicals is provided by the carbohydrate, metabolism in the muscle., Resynthesis of ATP by carbohydrate metabolism, Carbohydrate metabolism starts with catabolic reactions, of glycogen in the muscle. In resting muscle, an adequate, amount of glycogen is stored in sarcoplasm., Each molecule of glycogen undergoes catabolism, to, produce ATP. The energy liberated during the catabolism, of glycogen can cause muscular contraction for a longer, period. The first stage of catabolism of glycogen is via, glycolysis. It is called glycolytic pathway or EmbdenMeyerhof pathway (Fig. 31.10)., Glycolysis, Each glycogen molecule is converted into 2 pyruvic acid, molecules. Only small amount of ATP (2 molecules) is, synthesized in this pathway., This pathway has 10 steps. Each step is catalyzed, by one or two enzymes as shown in Figure 31.10., During glycolysis, 4 hydrogen atoms are released, which are also utilized for formation of additional, molecules of ATP. Formation of ATP by the utilization of, hydrogen is explained later., Further changes in pyruvic acid depend upon the, availability of oxygen. In the absence of oxygen, the
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198 Section 3 t Muscle Physiology, pyruvic acid is converted into lactic acid that enters the, Cori cycle. It is known as anerobic glycolysis. If oxygen, is available, the pyruvic acid enters into Krebs cycle. It, is known as aerobic glycolysis., Cori cycle, Lactic acid is transported to liver where it is converted, into glycogen and stored there. If necessary, glycogen, breaks into glucose, which is carried by blood to muscle., Here, the glucose is converted into glycogen, which, enters the EmbdenMeyerhof pathway (Figs 31.11 and, 31.12)., Krebs cycle, Krebs cycle is otherwise known as tricarboxylic acid, cycle (TCA cycle) or citric acid cycle. A greater amount, of energy is liberated through this cycle. The pyruvic acid, derived from glycolysis is taken into mitochondria where, it is converted into acetyl coenzyme A with release of, 4 hydrogen atoms. The acetyl coenzyme A enters the, Krebs cycle., Krebs cycle is a series of reactions by which acetyl, coenzyme A is degraded in various steps to form carbon, , FIGURE 31.11: Cori cycle, , FIGURE 31.12: Schematic diagram showing carbohydrate, metabolism in muscle, , dioxide and hydrogen atoms. All these reactions occur, in the matrix of mitochondrion. During Krebs cycle, 2, molecules of ATP and 16 atoms of hydrogen are released. Hydrogen atoms are also utilized for the formation, of ATP (see below)., Significance of Hydrogen Atoms Released, during Carbohydrate Metabolism, , FIGURE 31.10: Glycolysis/EmbdenMeyerhof pathway, Number of ATP molecules formed in this pathway:, Total ATP formed, = 4 molecules, Loss of ATP during phosphorylation = 2 molecules, Net ATP formed during glycolysis, = 2 molecules, , Altogether 24 hydrogen atoms are released during, glycolysis and Krebs cycle:, 4H : During breakdown of glycogen into pyruvic, acid, 4H : During formation of acetyl coenzyme A from, pyruvic acid, 16H : During degradation of acetyl coenzyme A in, Krebs cycle.
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Chapter 31 t Changes during Muscular Contraction 199, Hydrogen atoms are released in the form of two, pockets into intracellular fluid and it is catalyzed by the, enzyme dehydrogenase. Once released, 20 hydrogen, atoms combine with nicotinamide adenine dinucleotide, (NAD), which acts as hydrogen carrier. NAD transfers, the hydrogen atoms to the cytochrome system where, oxidative phosphorylation takes place. Oxidative phosphorylation is the process during which the ATP mole, cules are formed by utilizing hydrogen atoms., For every 2 hydrogen atoms 3 molecules of ATP, are formed. So, from 20 hydrogen atoms 30 molecules, of ATP are formed. Remaining 4 hydrogen atoms enter, the oxidative phosphorylation processes directly without, combining with NAD. Only 2 ATP molecules are formed, for every 2 hydrogen atoms. So, 4 hydrogen atoms, give rise to 4 ATP molecules. Thus, 34 ATP molecules, are formed from the hydrogen atoms released during, glycolysis and Krebs cycle., Summary of Resynthesis of ATP during, Carbohydrate Metabolism, A total of 38 ATP molecules are formed during breakdown, of each glycogen molecule in the muscle as summarized, below:, During glycolysis, : 2 molecules of ATP, During Krebs cycle, : 2 molecules of ATP, By utilization of hydrogen : 34 molecules of ATP, Total, : 38 molecules of ATP, CHANGES IN pH DURING, MUSCULAR CONTRACTION, Reaction and the pH of muscle are altered in different, stages of muscular contraction., In Resting Condition, During resting condition, the reaction of muscle is, alkaline with a pH of 7.3., During Onset of Contraction, At the beginning of the muscular contraction, the reaction, becomes acidic. The acidity is due to dephosphorylation, of ATP into ADP and Pi., During Later Part of Contraction, During the later part of contraction, the muscle becomes, alkaline. It is due to the resynthesis of ATP from CP., At the End of Contraction, At the end of contraction, the muscle becomes once, again acidic. This acidity is due to the formation of, pyruvic acid and/or lactic acid., , THERMAL CHANGES DURING MUSCULAR, CONTRACTION, During muscular contraction, heat is produced. Not all, the heat is liberated at a time. It is released in different, stages:, 1. Resting heat, 2. Initial heat, 3. Recovery heat., RESTING HEAT, Heat produced in the muscle at rest is called the resting, heat. It is due to the basal metabolic process in the, muscle., INITIAL HEAT, During muscular activity, heat production occurs in three, stages:, i. Heat of activation, ii. Heat of shortening, iii. Heat of relaxation., i. Heat of Activation, Heat of activation is the heat produced before the actual, shortening of the muscle fibers. Most of this heat is, produced during the release of calcium ions from ‘L’, tubules. It is also called maintenance heat., ii. Heat of Shortening, Heat of shortening is the heat produced during contraction, of muscle. The heat is produced due to various structural, changes in the muscle fiber like movements of cross, bridges and myosin heads and breakdown of glycogen., iii. Heat of Relaxation, Heat released during relaxation of the muscle is known, as the heat of relaxation. In fact, it is the heat produced, during the contraction of muscle due to breakdown of, ATP molecule. It is released when the muscle lengthens, during relaxation., RECOVERY HEAT, Recovery heat is the heat produced in the muscle, after the end of activities. After the end of muscular, activities, some amount of heat is produced due to the, chemical processes involved in resynthesis of chemical, substances broken down during contraction.
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Neuromuscular Junction, , Chapter, , 32, , DEFINITION AND STRUCTURE, , , , DEFINITION, STRUCTURE, , NEUROMUSCULAR TRANSMISSION, , , , , , , RELEASE OF ACETYLCHOLINE, ACTION OF ACETYLCHOLINE, ENDPLATE POTENTIAL, MINIATURE ENDPLATE POTENTIAL, FATE OF ACETYLCHOLINE, , NEUROMUSCULAR BLOCKERS, DRUGS STIMULATING NEUROMUSCULAR JUNCTION, MOTOR UNIT, , , , , DEFINITION, NUMBER OF MUSCLE FIBERS IN MOTOR UNIT, RECRUITMENT OF MOTOR UNITS, , APPLIED PHYSIOLOGY – DISORDERS OF NEUROMUSCULAR JUNCTION, , , , MYASTHENIA GRAVIS, EATON-LAMBERT SYNDROME, , DEFINITION AND STRUCTURE, DEFINITION, Neuromuscular junction is the junction between terminal, branch of the nerve fiber and muscle fiber., , This portion of the axis cylinder is expanded like a bulb,, which is called motor endplate., Axon terminal contains mitochondria and synaptic, vesicles. Synaptic vesicles contain the neurotransmitter, , STRUCTURE, Skeletal muscle fibers are innervated by the motor, nerve fibers. Each nerve fiber (axon) divides into many, terminal branches. Each terminal branch innervates, one muscle fiber through the neuromuscular junction, (Fig. 32.1)., Axon Terminal and Motor Endplate, Terminal branch of nerve fiber is called axon terminal., When the axon comes close to muscle fiber, it loses, the myelin sheath. So, the axis cylinder is exposed., , FIGURE 32.1: Longitudinal section of neuromuscular junction
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Chapter 32 t Neuromuscular Junction 201, substance, acetylcholine (Ach). The Ach is synthesized, by mitochondria present in the axon terminal and stored, in the vesicles. Mitochondria contain ATP, which is the, source of energy for the synthesis of acetylcholine., Synaptic Trough or Gutter, Motor endplate invaginates inside the muscle fiber and, forms a depression, which is known as synaptic trough, or synaptic gutter. The membrane of the muscle fiber, below the motor endplate is thickened., Synaptic Cleft, Membrane of the nerve ending is called the presynaptic, membrane. Membrane of the muscle fiber is called, postsynaptic membrane. Space between these two, membranes is called synaptic cleft., Synaptic cleft contains basal lamina. It is a thin layer, of spongy reticular matrix through which, the extracellular, fluid diffuses. An enzyme called acetylcholinesterase, (AchE) is attached to the matrix of basal lamina, in large, quantities., Subneural Clefts, Postsynaptic membrane is the membrane of the muscle, fiber. It is thrown into numerous folds called subneural, clefts. Postsynaptic membrane contains the receptors, called nicotinic acetylcholine receptors (Fig. 32.2)., , NEUROMUSCULAR TRANSMISSION, Definition, Neuromuscular transmission is defined as the transfer of, information from motor nerve ending to the muscle fiber, through neuromuscular junction. It is the mechanism, , by which the motor nerve impulses initiate muscle, contraction., Events of Neuromuscular Transmission, A series of events take place in the neuromuscular, junction during this process (Fig. 32.3). The events are:, 1. Release of acetylcholine, 2. Action of acetylcholine, 3. Development of endplate potential, 4. Development of miniature endplate potential, 5. Destruction of acetylcholine., 1. RELEASE OF ACETYLCHOLINE, When action potential reaches axon terminal, it opens, the voltage-gated calcium channels in the membrane, of axon terminal. Calcium ions from extracellular fluid, (ECF) enter the axon terminal. These cause bursting of, the vesicles by forcing the synaptic vesicles move and, fuse with presynaptic membrane. Now, acetylcholine, is released from the ruptured vesicles. By exocytosis,, acetylcholine diffuses through the presynaptic membrane and enters the synaptic cleft., Each vesicle contains about 10,000 acetylcholine, molecules. And, at a time, about 300 vesicles open and, release acetylcholine., 2. ACTION OF ACETYLCHOLINE, After entering the synaptic cleft, acetylcholine molecules, bind with nicotinic receptors present in the postsynaptic, membrane and form acetylcholine-receptor complex. It, increases the permeability of postsynaptic membrane for, sodium by opening the ligand-gated sodium channels., Now, sodium ions from ECF enter the neuromuscular, junction through these channels. And there, sodium, ions alter the resting membrane potential and develops, the electrical potential called the endplate potential., 3. DEVELOPMENT OF ENDPLATE POTENTIAL, Endplate potential is the change in resting membrane, potential when an impulse reaches the neuromuscular, junction. Resting membrane potential at neuromuscular, junction is –90 mV. When sodium ions enter inside,, slight depolarization occurs up to –60 mV, which is, called endplate potential., Properties of Endplate Potential, , FIGURE 32.2: Structure of neuromuscular junction, , Endplate potential is a graded potential (Chapter 31), and it is not action potential. Refer Table 31.1 for the, properties of graded potential.
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202 Section 3 t Muscle Physiology, Miniature endplate potential cannot produce action, potential in the muscle. When more and more quanta of, acetylcholine are released continuously, the miniature, endplate potentials are added together and finally, produce endplate potential resulting in action potential, in the muscle., 5. DESTRUCTION OF ACETYLCHOLINE, Acetylcholine released into the synaptic cleft is destroyed very quickly, within one millisecond by the enzyme,, acetylcholinesterase. However, the acetylcholine is so, potent, that even this short duration of 1 millisecond is, sufficient to excite the muscle fiber. Rapid destruction, of acetylcholine has got some important functional, significance. It prevents the repeated excitation of the, muscle fiber and allows the muscle to relax., Reuptake Process, Reuptake is a process in neuromuscular junction,, by which a degraded product of neurotransmitter reenters the presynaptic axon terminal where it is reused., Acetylcholinesterase splits (degrades) acetylcholine, into inactive choline and acetate. Choline is taken, back into axon terminal from synaptic cleft by reuptake, process. There, it is reused in synaptic vesicle to form, new acetylcholine molecule., , NEUROMUSCULAR BLOCKERS, , FIGURE 32.3: Sequence of events during neuromuscular, transmission. Ach = Acetylcholine, ECF = Extracellular fluid., , Significance of Endplate Potential, Endplate potential is non-propagative. But it causes the, development of action potential in the muscle fiber., 4. DEVELOPMENT OF MINIATURE, ENDPLATE POTENTIAL, Miniature endplate potential is a weak endplate potential, in neuromuscular junction that is developed by the, release of a small quantity of acetylcholine from axon, terminal. And, each quantum of this neurotransmitter, produces a weak miniature endplate potential. The, amplitude of this potential is only up to 0.5 mV., , Neuromuscular blockers are the drugs, which prevent, transmission of impulses from nerve fiber to the muscle, fiber through the neuromuscular junctions. These, drugs are used widely during surgery and trauma, care. Neuromuscular blockers used during anesthesia, relax the skeletal muscles and induce paralysis so that, surgery can be conducted with less complication., Following are important neuromuscular blockers,, which are commonly used in clinics and research., 1. Curare, Curare prevents the neuromuscular transmission, by combining with acetylcholine receptors. So, the, acetylcholine cannot combine with the receptors. And,, the endplate potential cannot develop. Since curare, blocks the neuromuscular transmission by acting on the, acetylcholine receptors, it is called receptor blocker., 2. Bungarotoxin, Bungarotoxin is a toxin from the venom of deadly, snakes. It affects the neuromuscular transmission by, blocking the acetylcholine receptors.
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Chapter 32 t Neuromuscular Junction 203, 3. Succinylcholine and Carbamylcholine, These drugs block the neuromuscular transmission by, acting like acetylcholine and keeping the muscle in a, depolarized state. But, these drugs are not destroyed by, cholinesterase. So, the muscle remains in a depolarized, state for a long time., 4. Botulinum Toxin, Botulinum toxin is derived from the bacteria Clostridium, botulinum. It prevents release of acetylcholine from, axon terminal into the neuromuscular junction., , DRUGS STIMULATING, NEUROMUSCULAR JUNCTION, Neuromuscular junction can be stimulated by some, drugs like neostigmine, physostigmine and diisopropyl, fluorophosphate. These drugs inactivate the enzyme,, acetylcholinesterase. So, the acetylcholine is not hydrolyzed. It leads to repeated stimulation and continuous, contraction of the muscle., , MOTOR UNIT, DEFINITION, Single motor neuron, its axon terminals and the muscle, fibers innervated by it are together called motor unit., Each motor neuron activates a group of muscle fibers, through the axon terminals. Stimulation of a motor, neuron causes contraction of all the muscle fibers, innervated by that neuron., NUMBER OF MUSCLE FIBERS IN, MOTOR UNIT, Number of muscle fiber in each motor unit varies. The, motor units of the muscles concerned with fine, graded, , and precise movements have smaller number of muscle, fibers., For example,, Laryngeal muscles : 2 to 3 muscle fibers per motor unit, Pharyngeal muscles : 2 to 6 muscle fibers per motor unit, Ocular muscles, : 3 to 6 muscle fibers per motor unit, Muscles concerned with crude or coarse movements have motor units with large number of muscle, fibers. There are about 120 to 165 muscle fibers in each, motor unit in these muscles. Examples are the muscles, of leg and back., RECRUITMENT OF MOTOR UNITS, While stimulating the muscle with weak strength, only, a few motor units are involved. When the strength of, stimulus is increased, many motor units are put into, action. So, the force of contraction increases. The, process by which more and more motor units are put, into action is called recruitment of motor unit. Thus, the, graded response in the muscle is directly proportional to, the number of motor units activated., Activation of motor units can be studied by, electromyography., , APPLIED PHYSIOLOGY – DISORDERS, OF NEUROMUSCULAR JUNCTION, MYASTHENIA GRAVIS, Myasthenia gravis is an autoimmune disorder of, neuromuscular junction caused by antibodies to, cholinergic receptors. Refer Chapter 34 for details., EATON-LAMBERT SYNDROME, Eaton-Lambert syndrome is also an autoimmune, disorder of neuromuscular junction. It is caused by, antibodies to calcium channels in axon terminal. Refer, Chapter 34 for details.
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Chapter, , Smooth Muscle, , , , , , , , , , , 33, , DISTRIBUTION, FUNCTIONS, STRUCTURE, TYPES, ELECTRICAL ACTIVITY IN SINGLE-UNIT SMOOTH MUSCLE, ELECTRICAL ACTIVITY IN MULTIUNIT SMOOTH MUSCLE, CONTRACTILE PROCESS, NEUROMUSCULAR JUNCTION, CONTROL OF SMOOTH MUSCLE, , DISTRIBUTION OF SMOOTH MUSCLE, , IN CARDIOVASCULAR SYSTEM, , Smooth muscles are non-striated (plain) and involuntary, muscles. These muscles are present in almost all the, organs in the form of sheets, bundles or sheaths around, other tissues. Smooth muscles form the major contractile, tissues of various organs., Structures in which smooth muscle fibers are, present:, 1. Wall of organs like esophagus, stomach and, intestine in the gastrointestinal tract, 2. Ducts of digestive glands, 3. Trachea, bronchial tube and alveolar ducts of, respiratory tract, 4. Ureter, urinary bladder and urethra in excretory, system, 5. Wall of the blood vessels in circulatory system, 6. Arrector pilorum of skin, 7. Mammary glands, uterus, genital ducts, prostate, gland and scrotum in the reproductive system, 8. Iris and ciliary body of the eye., , Smooth muscle fibers around the blood vessels regulate, blood pressure and blood flow through different organs, and regions of the body., , FUNCTIONS OF SMOOTH MUSCLE, Smooth muscles are concerned with very important, functions in different parts of the body., , IN RESPIRATORY SYSTEM, Contraction and relaxation of smooth muscle fibers of, the air passage alter the diameter of air passage and, regulate the inflow and outflow of air., IN DIGESTIVE SYSTEM, Smooth muscle fibers in digestive tract help in movement of food substances, mixing of food substance with, digestive juices, absorption of digested material and, elimination of unwanted substances. Sphincters along, the digestive tract regulate the flow of materials., IN RENAL SYSTEM, Smooth muscle fibers in renal blood vessels regulate, renal blood flow and glomerular filtration. Smooth, muscles in the ureters propel urine from kidneys to, urinary bladder through ureters. Smooth muscles present, in urinary bladder help voiding urine to the exterior.
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Chapter 33 t Smooth Muscle 205, IN REPRODUCTIVE SYSTEM, In males, smooth muscle fibers facilitate the movement, of sperms and secretions from accessory glands along, the reproductive tract. In females, these muscles, accelerate the movement of sperms through genital, tract after sexual act, movement of ovum into uterus, through fallopian tube, expulsion of menstrual fluid and, delivery of the baby., , STRUCTURE OF SMOOTH MUSCLE, Smooth muscle fibers are fusiform or elongated cells., These fibers are generally very small, measuring 2 to, 5 microns in diameter and 50 to 200 microns in length., Nucleus is single and elongated and it is centrally, placed. Normally, two or more nucleoli are present in, the nucleus (Fig. 33.1)., , dense bodies. It helps to transmit the contraction from, one cell to another throughout the tissue., , Myofibrils and Sarcomere, , Covering and Tendons, , Well-defined myofibrils and sarcomere are absent in, smooth muscles. So the alternate dark and light bands, are absent. Absence of dark and light bands gives the, non-striated appearance to the smooth muscle., , Smooth muscle fibers are covered by connective tissue., But the tendons and aponeurosis are absent., , Myofilaments and Contractile Proteins, Contractile proteins in smooth muscle fiber are actin,, myosin and tropomyosin. But troponin or troponin-like, substance is absent., Thick and thin filaments are present in smooth, muscle. However, these filaments are not arranged in, orderly fashion as in skeletal muscle. Thick filaments, are formed by myosin molecules and are scattered in, sarcoplasm. These thick filaments contain more number, of cross bridges than in skeletal muscle. Thin filaments, are formed by actin and tropomyosin molecules., Dense Bodies, Dense bodies are the special structures of smooth, muscle fibers to which the actin and tropomyosin, molecules of thin filaments are attached. The dense, bodies are scattered all over the sarcoplasm in the, network of intermediate filaments, which is formed by, the protein desmin. Some of the dense bodies are firmly, attached with sarcolemma. The anchoring of the dense, bodies, intermediate filaments and thin filaments make, the smooth muscle fiber shorten when sliding occurs, between thick and thin filaments., Another interesting feature is that the dense bodies, are not arranged in straight line. Because of this, smooth, muscle fibers twist like corkscrew during contraction., Adjacent smooth muscle fibers are bound together at, , FIGURE 33.1: Smooth muscle fibers, , Sarcotubular System, Sarcotubular system in smooth muscle fibers is in the, form of network. ‘T’ tubules are absent and ‘L’ tubules, are poorly developed (see Table 28.1)., , TYPES OF SMOOTH MUSCLE FIBERS, Smooth muscle fibers are of two types:, 1. Single-unit or visceral smooth muscle fibers, 2. Multiunit smooth muscle fibers., SINGLE-UNIT OR VISCERAL, SMOOTH MUSCLE FIBERS, Single-unit smooth muscle fibers are the fibers with, interconnecting gap junctions. The gap junctions allow, rapid spread of action potential throughout the tissue so, that all the muscle fibers show synchronous contraction, as a single unit. Single unit smooth muscle fibers are, also called visceral smooth muscle fibers., Features of single-unit smooth muscle fibers:, 1. Muscle fibers are arranged in sheets or bundles, 2. Cell membrane of adjacent fibers fuses at many, points to form gap junctions. Through the gap, junctions, ions move freely from one cell to the, other. Thus a functional syncytium is developed., The syncytium contracts as a single unit. In this, way, the visceral smooth muscle resembles cardiac, muscle more than the skeletal muscle.
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206 Section 3 t Muscle Physiology, Distribution of Single-unit Smooth Muscle Fibers, Visceral smooth muscle fibers are in the walls of the, organs such as gastrointestinal organs, uterus, ureters,, respiratory tract, etc., MULTIUNIT SMOOTH MUSCLE FIBERS, Multiunit smooth muscle fibers are the muscle fibers, without interconnecting gap junctions. These smooth, muscle fibers resemble the skeletal muscle fibers in, many ways., Features of multiunit smooth muscle fibers:, 1. Muscle fibers are individual fibers, 2. Each muscle fiber is innervated by a single nerve, ending, 3. Each muscle fiber has got an outer membrane, made up of glycoprotein, which helps to insulate, and separate the muscle fibers from one another, 4. Control of these muscle fibers is mainly by nerve, signals, 5. These smooth muscle fibers do not exhibit, spontaneous contractions., Distribution of Multiunit Smooth Muscle Fibers, Multiunit muscle fibers are in ciliary muscles of the eye,, iris of the eye, nictitating membrane (in cat), arrector, pili and smooth muscles of the blood vessels and, urinary bladder., , ELECTRICAL ACTIVITY IN, SINGLE-UNIT SMOOTH MUSCLE, Usually 30 to 40 smooth muscle fibers are simultaneously, depolarized, which leads to development of selfpropagating action potential. It is possible because of, gap junctions and syncytial arrangements of single-unit, smooth muscles., RESTING MEMBRANE POTENTIAL, Resting membrane potential in visceral smooth muscle, is very unstable and ranges between –50 and –75 mV., Sometimes, it reaches the low level of –25 mV., CAUSE FOR UNSTABLE RESTING MEMBRANE, POTENTIAL – SLOW-WAVE POTENTIAL, The unstable resting membrane potential is caused by, the appearance of some wave-like fluctuations called, slow waves. The slow waves occur in a rhythmic fashion, at a frequency of 4 to 10 per minute with the amplitude, , of 10 to 15 mV (Fig. 33.2). The cause of the slow-wave, rhythm is not known. It is suggested that it may be due, to the rhythmic modulations in the activities of sodiumpotassium pump. The slow wave is not action potential, and it cannot cause contraction of the muscle. But it, initiates the action potential (see below)., ACTION POTENTIAL, Three types of action potential occur in visceral smooth, muscle fibers:, 1. Spike potential, 2. Spike potential initiated by slow-wave rhythm, 3. Action potential with plateau., 1. Spike Potential, Spike potential in visceral smooth muscle appears, similar to that of skeletal muscle. However, it is different, from the spike potential in skeletal muscles in many, ways. In smooth muscle, the average duration of spike, potential varies between 30 and 50 milliseconds. Its, amplitude is very low and it does not reach the isoelectric, base. Sometimes, the spike potential rises above the, isoelectric base (overshoot). The spike potential is due, to nervous and other stimuli and it leads to contraction, of the muscle., 2. Spike Potential Initiated by, Slow-wave Rhythm, Sometimes the slow-wave rhythm of resting membrane, potential initiates the spike potentials, which lead to, contraction of the muscle. The spike potentials appear, rhythmically at a rate of about one or two spikes at the, peak of each slow wave. The spike potentials initiated, by the slow-wave rhythm cause rhythmic contractions, of smooth muscles. This type of potentials appears, mostly in smooth muscles, which are self-excitatory, and contract themselves without any external stimuli., So, the spike potentials initiated by slow-wave rhythm, are otherwise called pacemaker waves. The smooth, muscles showing rhythmic contractions are present in, some of the visceral organs such as intestine., 3. Action Potential with Plateau, This type of action potential starts with rapid depolarization as in the case of skeletal muscle. But, repolarization does not occur immediately. The muscle remains, depolarized for long periods of about 100 to 1,000, milliseconds. This type of action potential is responsible, for sustained contraction of smooth muscle fibers. After, the long depolarized state, slow repolarization occurs.
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Chapter 33 t Smooth Muscle 207, , FIGURE 33.2: Electrical activities in smooth muscle, A = Slow-wave rhythm of resting membrane potential, B = Spike potential, C = Spike potential initiated by slow wave rhythm, D = Action potential with plateau, , TONIC CONTRACTION OF SMOOTH, MUSCLE WITHOUT ACTION POTENTIAL, Smooth muscles of some visceral organs maintain a, state of partial contraction called tonus or tone. It is, due to the tonic contraction of the muscle that occurs, without any action potential or any stimulus. Sometimes,, the tonic contraction occurs due to the action of some, hormones., IONIC BASIS OF ACTION POTENTIAL, The important difference between action potential in, skeletal muscle and smooth muscle lies in the ionic basis, of depolarization. In skeletal muscle, the depolarization, occurs due to opening of sodium channels and entry, , of sodium ions from extracellular fluid into the muscle, fiber. But in smooth muscle, the depolarization is due to, entry of calcium ions rather than sodium ions. Unlike the, fast sodium channels, the calcium channels open and, close slowly. It is responsible for the prolonged action, potential with plateau in smooth muscles. The calcium, ions play an important role during the contraction of the, muscle., , ELECTRICAL ACTIVITY IN, MULTIUNIT SMOOTH MUSCLE, Electrical activity in multiunit smooth muscle is different, from that in the single unit smooth muscle. Electrical, changes leading to contraction of multiunit smooth
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208 Section 3 t Muscle Physiology, muscle are triggered by nervous stimuli. Nerve endings, secrete the neurotransmitters like acetylcholine and, noradrenaline. Neurotransmitters depolarize the, membrane of smooth muscle fiber slightly leading to, contraction. The action potential does not develop. This, type of depolarization is called local depolarization, or excitatory junctional potential (EJP). This local, depolarization travels throughout the entire smooth, muscle fiber and causes contraction. Local depolarization, is developed because the multiunit smooth muscle fibers, are too small to develop action potential., , CONTRACTILE PROCESS IN, SMOOTH MUSCLE, Compared to skeletal muscles, in smooth muscles,, the contraction and relaxation processes are slow. The, latent period is also long. Thus, the total twitch period, is very long and it is about 1 to 3 seconds. In skeletal, muscle, the total twitch period is 0.1 sec., MOLECULAR BASIS OF SMOOTH, MUSCLE CONTRACTION, The process of excitation and contraction is very slow, in smooth muscles because of poor development of ‘L’, tubules (sarcoplasmic reticulum). So, the calcium ions,, which are responsible for excitation-contraction coupling, must be obtained from the extracellular fluid. It makes, the process of excitation-contraction coupling slow., , Relaxation of the muscle occurs due to dissociation, of calcium-calmodulin complex., Length-Tension Relationship – Plasticity, Plasticity is the adaptability of smooth muscle fibers to, a wide range of lengths. If the smooth muscle fiber is, stretched, it adapts to this new length and contracts when, stimulated. Because of this property, tension produced, in the muscle fiber is not directly proportional to resting, length of the muscle fiber. In other words, Starling’s, law is not applicable to smooth muscle. Starling’s law, is applicable in skeletal and cardiac muscles and the, tension or force of contraction is directly proportional to, initial length of fibers in these muscles., The property of plasticity in smooth muscle fibers is, especially important in digestive organs such as stomach,, which undergo remarkable changes in volume., In spite of plasticity, smooth muscle fibers contract, powerfully like the skeletal muscle fibers. Smooth, muscle fibers also show sustained tetanic contractions, like skeletal muscle fibers., , NEUROMUSCULAR JUNCTION, IN SMOOTH MUSCLE, Well-defined neuromuscular junctions are absent in, smooth muscle. The nerve fibers (axons) do not end in the, , Calcium-calmodulin Complex, Stimulation of ATPase activity of myosin in smooth, muscle is different from that in the skeletal muscle. In, smooth muscle, the myosin has to be phosphorylated, for the activation of myosin ATPase., Phosphorylation of myosin occurs in the following, manner:, 1. Calcium, which enters the sarcoplasm from the, extracellular fluid combines with a protein called, calmodulin and forms calcium-calmodulin complex, (Fig. 33.3), 2. It activates calmodulin-dependent myosin light, chain kinase, 3. This enzyme in turn causes phosphorylation of, myosin followed by activation of myosin ATPase, 4. Now, the sliding of actin filaments starts., Phosphorylated myosin gets attached to the actin, molecule for longer period. It is called latch-bridge, mechanism and it is responsible for the sustained, contraction of the muscle with expenditure of little, energy., , FIGURE 33.3: Molecular basis of smooth muscle contraction
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Chapter 33 t Smooth Muscle 209, form of endplate. Instead, these nerve fibers end on, smooth muscle fibers in three different ways:, 1. Nerve fibers diffuse on the sheet of smooth muscle, fibers without making any direct contact with the, muscle. The diffused nerve fibers form diffuse, junctions, which contain neurotransmitters., Neurotransmitters are released into the matrix,, which coats the smooth muscle fiber. From here, the neurotransmitters enter the muscle fibers, 2. In some smooth muscle fibers, the axon terminal ends in the form of many varicosities. The, varicosities have vesicles, which contain the, neurotransmitter. Neurotransmitter is released, from varicosities through their wall into the, muscle fiber, 3. In some of the multiunit smooth muscle fibers,, a gap is present between varicosities and the, membrane of smooth muscle fibers, which, resembles the synaptic cleft in skeletal muscle., The width of this gap is 30 to 40 nm. This gap, is called contact junction and it functions as, neuromuscular junction of skeletal muscle., , CONTROL OF SMOOTH MUSCLE, Smooth muscle fibers are controlled by:, 1. Nervous factors, 2. Humoral factors., NERVOUS FACTORS, Smooth muscles are supplied by both sympathetic and, parasympathetic nerves, which antagonize (act opposite, to) each other and control the activities of smooth muscles. However, these nerves are not responsible for the, initiation of any activity in smooth muscle. The tonus of, smooth muscles is also independent of nervous control., HUMORAL FACTORS, Activity of smooth muscle is also controlled by humoral, factors, which include hormones, neurotransmitters and, other humoral factors., , Hormones and Neurotransmitters, Action of the hormones and neurotransmitters depends, upon the type of receptors present in membrane of, smooth muscle fibers in particular area. The receptors, are of two types, excitatory receptors and inhibitory, receptors., If excitatory receptors are present, the hormones or, the neurotransmitters contract the muscle by producing, depolarization. If inhibitory receptors are present, the, hormones or the neurotransmitters relax the muscles by, producing hyperpolarization., Hormones and neurotransmitters, which act on, smooth muscles are:, 1. Acetylcholine, 2. Antidiuretic hormone (ADH), 3. Adrenaline, 4. Angiotensin II, III and IV, 5. Endothelin, 6. Histamine, 7. Noradrenaline, 8. Oxytocin, 9. Serotonin., Other Humoral Factors, Humoral factors other than the hormones cause, relaxation of smooth muscle fibers., Humoral factors which relax the smooth muscles:, 1. Lack of oxygen, 2. Excess of carbon dioxide, 3. Increase in hydrogen ion concentration, 4. Adenosine, 5. Lactic acid, 6. Excess of potassium ion, 7. Decrease in calcium ion, 8. Nitric oxide (NO), the endothelium-derived relaxing, factor (EDRF).
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Electromyogram and, Disorders of Skeletal Muscle, , , , , , Chapter, , 34, , DEFINITION, ELECTROMYOGRAPHIC TECHNIQUE, ELECTROMYOGRAM, DISORDERS OF SKELETAL MUSCLE – MYOPATHY, , , , , , , , , MUSCULAR DYSTROPHY, DISEASES INVOLVING MUSCLE TONE, FIBRILLATION AND DENERVATION HYPERSENSITIVITY, MYASTHENIA GRAVIS, LAMBERT-EATON SYNDROME, McARDLE DISEASE, MITOCHONDRIAL MYOPATHY, NEMALINE MYOPATHY, , DEFINITION, Electromyography is the study of electrical activity of, the muscle. Electromyogram (EMG) is the graphical, registration of the electrical activity of the muscle., , ELECTROMYOGRAPHIC TECHNIQUE, Cathode ray oscilloscope or a polygraph is used to record, the electromyogram. Two types of electrodes are used, for recording the electrical activities of the muscle:, 1. Surface electrode or skin electrode for studying the, activity of a muscle., 2. Needle electrodes for studying the electrical activity, of a single motor unit., , less. When the force increases, larger potentials are, obtained due to the recruitment of more and more, number of motor neurons., Uses of Electromyogram, Electromyogram is useful in the diagnosis of neuro, muscular diseases such as motor neuron lesions,, peripheral nerve injury and myopathies., , ELECTROMYOGRAM, Structural basis for electromyogram is the motor unit., Electrical potential developed by the activation of one, motor unit is called motor unit potential. It lasts for 5 to 8, milliseconds and has an amplitude of 0.5 mV. Mostly it, is monophasic (Fig. 34.1)., Electrical potential recorded from the whole muscle, shows smaller potentials if the force of contraction is, , FIGURE 34.1: Electromyogram during alternate contraction, and relaxation of biceps muscle
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Chapter 34 t Electromyogram and Disorders of Skeletal Muscle 211, , DISORDERS OF SKELETAL, MUSCLES – MYOPATHY, Myopathy is a muscular disorder in which the dysfunction, of muscle fiber leads to muscular weakness. Myopathies, may be acquired or genetically derived. These diseases, may or may not involve the nervous system., Common diseases of skeletal muscles are:, 1. Muscular dystrophy, 2. Diseases involving muscle tone, 3. Fibrillation and denervation hypersensitivity, 4. Myasthenia gravis, 5. LambertEaton syndrome, 6. McArdle disease, 7. Mitochondrial myopathy, 8. Nemaline myopathy., 1. MUSCULAR DYSTROPHY, Muscular dystrophy is a disease characterized by, progressive degeneration of muscle fibers, without, the involvement of nervous system. Mostly it has, a hereditary origin. The muscles fail to regenerate,, resulting in progressive weakness and confinement to a, wheelchair. Eventually, death occurs. Common types of, muscular dystrophy are Duchenne muscular dystrophy, and Becker muscular dystrophy., Duchenne Muscular Dystrophy, Duchenne muscular dystrophy is a sexlinked recessive, disorder. It is due to the absence of a gene product, called dystrophin in the X chromosome. Dystrophin is, necessary for the stability of sarcolemma. This disease, is characterized by degeneration and necrosis of muscle, fibers. The degenerated muscle fibers are replaced, by fat and fibrous tissue. Common symptom is the, muscular weakness. Sometimes, there is enlargement, of muscles (pseudohypertrophy). In severe conditions,, the respiratory muscles become weak, resulting in, difficulty in breathing and death., Becker Muscular Dystrophy, Becker muscular dystrophy is also a sexlinked disorder., It occurs due to the reduction in quantity or alteration, of dystrophin. Common features of this disorder, are slow progressive weakness of legs and pelvis,, pseudohypertrophy of calf muscles, difficulty in walking,, fatigue and mental retardation., 2. DISEASES INVOLVING MUSCLE TONE, Hypertonia, Hypertonia or hypertonicity is a muscular disease, characterized by increased muscle tone and inability of, the muscle to stretch., , Causes, Hypertonia occurs in upper motor neuron lesion (Chapter, 144). During the lesion of upper motor neuron, inhibition, of lower motor neurons (gammamotorneurons in the, spinal cord) is lost. It causes exaggeration of lower, motor neuron activity, resulting in hypertonia., In children, hypertonia is associated with cerebral, palsy (permanent disorder caused by brain damage,, which occurs at or before birth and is characterized by, muscular impairment). Here also, the motor pathway, is affected. Such children usually have speech and, language delays, with lack of communication skills., Hypertonia and spasticity, Hypertonia may be related to spasticity, but it is present, with or without spasticity. Spasticity is a motor disorder, characterized by stiffness of the certain muscles due, to continuous contraction. Hypertonicity is one of the, major symptoms of spasticity. Paralysis (complete loss, of function) of the muscle due to hypertonicity is called, spastic paralysis., In hypertonia, there is a resistance to passive, movement and it does not depend on velocity (the, speed at which the movement occurs), where as in, spasticity there is an increase in resistance to sudden, passive movement. It is velocity dependent, i.e. faster, the passive movement stronger the resistance., Hypotonia, Hypotonia is the muscular disease characterized by, decreased muscle tone. The tone of the muscle is, decreased or lost. Muscle offers very little resistance to, stretch. Muscle becomes flaccid (lack of firmness) and, the condition is called flaccidity., Causes, Major cause for hypotonia is lower motor neuron lesion, (Chapter 144). The paralysis of muscle with hypotonicity, is called flaccid paralysis and it results in wastage of, muscles., Hypotonia may also occur because of central, nervous system dysfunction, genetic disorders or, muscular disorders., Clinical conditions associated with hypotonia are:, i. Down syndrome (chromosomal disorder,, characterized by physical and learning, disabilities), ii. Myasthenia gravis (see below), iii. Kernicterus (brain damage caused by jaundice, in infants; Chapter 163), iv. Congenital cerebellar ataxia (incoordination), v. Muscular dystrophy
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212 Section 3 t Muscle Physiology, vi., vii., viii., ix., , Congenital hypothyroidism, Hypervitaminosis D, Rickets (Chapter 68), Infant botulism (paralysis due to botulinum toxin)., , Myotonia, Myotonia is a congenital disease characterized by continu, ous contraction of muscle and slow relaxation even after, the cessation of voluntary act. The main feature of this, disease is the muscle stiffness, which is sometimes, referred as cramps. Muscle relaxation is delayed., This type of muscular stiffness with delayed, relaxation causes discomfort during simple actions, like walking, grasping and chewing. The muscles are, enlarged (hypertrophy) because of the continuous, contraction. Myotonia sets in during early to late, childhood and it is not progressive., , 4. MYASTHENIA GRAVIS, Myasthenia gravis is an autoimmune disease of, neuromuscular junction caused by antibodies to cholin, ergic receptors. It is characterized by grave weakness, of the muscle due to the inability of neuromuscular, junction to transmit impulses from nerve to the muscle., It is a serious and sometimes a fatal disease., Causes, Myasthenia gravis is caused due to the development, of autoantibodies (IgG autoantibodies) against the, receptors of acetylcholine (Chapter 17). That is, the, body develops antibodies against its own acetylcholine, receptors. These antibodies prevent binging of, acetylcholine with it receptors or destroy the receptors., So, though the acetylcholine release is normal, it cannot, execute its action., , Cause, Myotonia is caused by mutation in the genes of channel, proteins in sarcolemma. Such disorders are called, channelopathies., , Symptoms, , Fibrillation, , Muscles which are more susceptible for myasthenia, gravis are muscles of neck, limbs, eyeballs and the, muscle responsible for eyelid movements, chewing,, swallowing, speech and respiration., Common symptoms are:, i. Slow and weak muscular contraction because, of the defective neuromuscular activity, ii. Inability to maintain the prolonged contraction of, skeletal muscle, iii. Quick fatigability when the patient attempts, repeated muscular contractions, iv. Weakness and fatigability of arms and legs, v. Double vision and droopy eyelids due to the, weakness of ocular muscles, vi. Difficulty in swallowing due to weakness of, throat muscles, vii. Difficulty in speech due to weakness of muscles, of speech., In severe conditions, there is paralysis of muscles., Patient dies mostly due to the paralysis of respiratory, muscles., , Fibrillation means fine irregular contractions of individual, muscle fibers., , Treatment, , Types, Myotonia is of two types:, i. Becker-type myotonia or generalized myotonia,, which is more common than Thomsentype, myotonia. It is an autosomal recessive disorder, produced by defective genes contributed by, both the parents, ii. Thomsen-type myotonia is relatively rare and it, is an autosomal recessive disorder produced by, defective gene contributed by one parent., 3. FIBRILLATION AND DENERVATION, HYPERSENSITIVITY, Denervation of a skeletal muscle (lower motor neuron, lesion) causes fibrillation with flaccid paralysis and, denervation hypersensitivity., , Denervation Hypersensitivity, After denervation, the muscle becomes highly sensitive, to acetylcholine, which is released from neuromuscular, junction. It is called denervation hypersensitivity., , Myasthenia gravis is treated by administration of cholin, esterase inhibitors such as neostigmine and pyridostigmine. These drugs inhibit cholinesterase, which, degrades acetylcholine. So acetylcholine remaining in the, synaptic cleft for long period can bind with its receptors.
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Chapter 34 t Electromyogram and Disorders of Skeletal Muscle 213, 5. LAMBERT-EATON SYNDROME, Lamberteaton syndrome is a disorder of neuromuscular, junction caused by development of antibodies against, calcium channel in the nerve terminal, resulting in, reduction in the release of quanta of acetylcholine. This, disease is commonly associated with carcinoma. So, it, is also called carcinomatous myopathy. This disease is, characterized by several features of myasthenia gravis., In addition, the patients have blurred vision and dry, mouth., 6. McARDLE DISEASE, McArdle disease is a glycogen storage disease (accu, mulation of glycogen in muscles) due to the mutation of, genes involving the muscle glycogen phosphorylase,, , necessary for the breakdown of glycogen in muscles., Muscular pain and stiffness are the common features of, this disease., 7. MITOCHONDRIAL MYOPATHY, Mitochondrial myopathy is an inherited disease due to, the defects in the mitochondria (which provide critical, source of energy) of muscle fibers., 8. NEMALINE MYOPATHY, Nemaline myopathy is a congenital myopathy charac, terized by microscopic changes and formation of small, rod-like structures in the muscle fibers. It is also called, nemaline-rod myopathy. The features are delayed deve, lopment of motor activities and weakness of muscles.
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Endurance of Muscle, , Chapter, , 35, , STRENGTH OF THE MUSCLE, , , TYPES OF MUSCLE STRENGTH, , POWER OF THE MUSCLE, ENDURANCE OF THE MUSCLE, , Three factors are essential for the contraction of skeletal, muscle:, 1. Strength of the muscle, 2. Power of the muscle, 3. Endurance of the muscle., Strength and power of the muscle are the two factors, which determine the endurance of the muscle. Power of, the muscle is developed by strength of the muscle, , STRENGTH OF THE MUSCLE, Maximum force that can be developed during contraction is known as strength of the muscle. It is defined, as the maximal contractile force produced per square, centimeter of the cross-sectional area of a skeletal, muscle. The normal force produced by a muscle is about, 3 to 4 kg/cm2 area of muscle. If the size of the muscle is, more, the strength developed also will be more., The size of the muscle can be increased either, by exercise or by some hormones like androgens. For, example, weight lifters will have the quadriceps muscle, with cross-sectional area of about 150 cm2. So, the total, strength of the quadriceps muscles is between 500 and, 550 kg/cm2., TYPES OF MUSCLE STRENGTH, Strength of the muscle is of two types:, 1. Contractile strength, 2. Holding strength., 1. Contractile Strength, Contractile strength is the strength of the muscle during, the actual contraction or shortening of muscle fibers. For, , example, while jumping, when a person takes his body, off the ground, there is contraction of the leg muscles., This is called the contractile strength., 2. Holding Strength, Holding strength is the force produced while stretching, the contracted muscles. For example, while landing, after jumping, the leg muscles are stretched. The force, developed by the muscles at that time is called the, holding strength. The holding strength is greater than, the contractile strength., , POWER OF THE MUSCLE, Amount of work done by the muscle in a given unit of, time is called the power. Power of the muscle depends, upon three factors. Muscle power is directly proportional, to these factors:, 1. Strength of the muscle., 2. Force of contraction., 3. Frequency of contraction., Muscle power is generally expressed in kilogrammeter per min (kg-m/min), i.e. the weight lifted by, a muscle to a height of 1 meter for one minute. The, maximum power achieved by all the muscles in the body, of a highly trained athlete, with all the muscles working, together is approximately,, First 8 to 10 seconds : 7,000 kg-m/min, Next 1 minute, : 4,000 kg-m/min, Next 30 minute, : 1,700 kg-m/min, This shows that the maximum power is developed, only for a short period of time.
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Chapter 35 t Endurance of Muscle 215, , ENDURANCE OF THE MUSCLE, Capacity of the muscle to withstand the power produced, during activity is called endurance. It depends mostly on, the supply of nutrition to the muscle., Most important nutritive substance for the muscle, is glycogen. This is actually stored in the muscle before, the beginning of the activity. More amount of glycogen, , can be stored in the muscles if a person takes diet, containing more carbohydrates than the diet containing, fat or a mixed diet. Following is the amount of glycogen, stored in the muscle in persons taking different diets., High carbohydrate diet : 40 gm/kg muscle, Mixed diet, : 20 gm/kg muscle, High fat diet, : 6 gm/kg muscle.
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216 Questions in Muscle Physiology, , QUESTIONS IN MUSCLE PHYSIOLOGY, , LONG QUESTIONS, 1. Enumerate the properties of muscles and give, an account on contractile property of the skeletal, muscle., 2. List the various changes taking place during, muscular contraction and explain the molecular, basis of contraction., 3. Write about the electrical changes during muscular, contraction., 4. Explain the ionic basis of electrical events during, contraction of skeletal muscle., 5. Describe the neuromuscular junction with a, suitable diagram. Add a note on neuromuscular, transmission, , SHORT QUESTIONS, 1., 2., 3., 4., 5., 6., 7., 8., 9., 10., 11., 12., 13., 14., , Compare skeletal muscle and cardiac muscle., Compare skeletal muscle and smooth muscle., Sarcomere., Contractile elements of the muscle., Muscle proteins., Sarcotubular system., Sarcoplasmic reticulum., Composition of muscle., Excitability or strength-duration curve., Factors affecting force of muscular contraction., Simple muscle curve., Latent period., Differences between pale and red muscles., Effects of two successive stimuli on muscle., , 15., 16., 17., 18., 19., 20., 21., 22., 23., 24., 25., 26., 27., 28., 29., 30., 31., 32., 33., 34., 35., 36., 37., 38., 39., 40., 41., 42., 43., 44., 45., , Effects of temperature variation on muscle., Rigor., Effects of repeated stimuli on skeletal muscle., Fatigue., Tetanus., Starling’s law of muscle., Refractory period., Muscle tone., Resting membrane potential., Action potential., Graded potential., Patch clamp., Actomyosin complex., Excitation-contraction coupling., Sliding theory of muscular contraction., Chemical changes during muscular contraction., Liberation of energy for muscular contraction., Thermal changes during muscular contraction., Electrical activity in smooth muscle., Molecular basis of smooth muscular contraction., Neuromuscular junction., Neuromuscular transmission., Endplate potential., Neuromuscular blockers., Motor unit., Electromyogram., Myopathy., Muscular dystrophy., Myasthenia gravis., Hypertonia., Hypotonia.
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Section, , 4, , 36., 37., 38., 39., 40., 41., 42., 43., 44., 45., 46., 47., , Digestive System, , Introduction to Digestive System ............................................................. 219, Mouth and Salivary Glands ..................................................................... 223, Stomach .................................................................................................. 230, Pancreas ................................................................................................. 241, Liver and Gallbladder .............................................................................. 249, Small Intestine ......................................................................................... 261, Large Intestine ........................................................................................ 266, Movements of Gastrointestinal Tract ....................................................... 270, Gastrointestinal Hormones ...................................................................... 281, Digestion, Absorption and Metabolism of Carbohydrates ....................... 287, Digestion, Absorption and Metabolism of Proteins .................................. 290, Digestion, Absorption and Metabolism of Lipids ..................................... 292
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Chapter, , Introduction to, Digestive System, , 36, , INTRODUCTION, FUNCTIONAL ANATOMY, WALL OF GASTROINTESTINAL TRACT, , , , , , MUCUS LAYER, SUBMUCUS LAYER, MUSCULAR LAYER, SEROUS OR FIBROUS LAYER, , NERVE SUPPLY TO GASTROINTESTINAL TRACT, , , , INTRINSIC NERVE SUPPLY, EXTRINSIC NERVE SUPPLY, , INTRODUCTION, Digestion is defined as the process by which food is, broken down into simple chemical substances that can, be absorbed and used as nutrients by the body. Most, of the substances in the diet cannot be utilized as such., These substances must be broken into smaller particles,, so that they can be absorbed into blood and distributed, to various parts of the body for utilization. Digestive, system is responsible for these functions., Digestive process is accomplished by mechanical, and enzymatic breakdown of food into simpler chemical compounds. A normal young healthy adult consumes, about 1 kg of solid diet and about 1 to 2 liter of liquid, diet every day. All these food materials are subjected to, digestive process, before being absorbed into blood and, distributed to the tissues of the body. Digestive system, plays the major role in the digestion and absorption of, food substances., Thus, the functions of digestive system include:, 1. Ingestion or consumption of food substances, 2. Breaking them into small particles, 3. Transport of small particles to different areas of the, digestive tract, 4. Secretion of necessary enzymes and other substances for digestion, , 5. Digestion of the food particles, 6. Absorption of the digestive products (nutrients), 7. Removal of unwanted substances from the body., , FUNCTIONAL ANATOMY OF, DIGESTIVE SYSTEM, Digestive system is made up of gastrointestinal tract, (GI tract) or alimentary canal and accessory organs,, which help in the process of digestion and absorption, (Fig. 36.1). GI tract is a tubular structure extending from, the mouth up to anus, with a length of about 30 feet. It, opens to the external environment on both ends., GI tract is formed by two types of organs:, 1. Primary digestive organs., 2. Accessory digestive organs., 1. Primary Digestive Organs, Primary digestive organs are the organs where actual, digestion takes place., Primary digestive organs are:, i. Mouth, ii. Pharynx, iii. Esophagus, iv. Stomach
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220 Section 4 t Digestive System, v. Small intestine, vi. Large intestine., 2. Accessory Digestive Organs, Accessory digestive organs are those which help primary digestive organs in the process of digestion., Accessory digestive organs are:, i. Teeth, ii. Tongue, iii. Salivary glands, iv. Exocrine part of pancreas, v. Liver, vi. Gallbladder., , Mucosa has three layer of structures:, i. Epithelial lining, ii. Lamina propria, iii. Muscularis mucosa., Epithelial Lining, Epithelial lining is in contact with the contents of GI tract., The type of cells in this layer varies in different parts of, GI tract. The inner surface of mouth, surface of tongue,, inner surface of pharynx and esophagus have stratified, squamous epithelial cells. However, mucus membrane, lining the other parts such as stomach, small intestine, and large intestine has columnar epithelial cells., , WALL OF GASTROINTESTINAL TRACT, , Lamina Propria, , In general, wall of the GI tract is formed by four layers, which are from inside out:, 1. Mucus layer, 2. Submucus layer, 3. Muscular layer, 4. Serous or fibrous layer., , Lamina propria is formed by connective tissues, which, contain fibroblasts, macrophages, lymphocytes and, eosinophils., , 1. MUCUS LAYER, Mucus layer is the innermost layer of the wall of GI, tract. It is also called gastrointestinal mucosa or mucus, membrane. It faces the cavity of GI tract., , Muscularis Mucosa, Muscularis mucosa layer consists of a thin layer of, smooth muscle fibers. It is absent in mouth and pharynx., It is present from esophagus onwards., 2. SUBMUCUS LAYER, Submucus layer is also present in all parts of GI tract,, except the mouth and pharynx. It contains loose collagen, fibers, elastic fibers, reticular fibers and few cells of, connective tissue. Blood vessels, lymphatic vessels and, nerve plexus are present in this layer., 3. MUSCULAR LAYER, , FIGURE 36.1: Gastrointestinal tract, , Muscular layer in lips, cheeks and wall of pharynx, contains skeletal muscle fibers. The esophagus has both, skeletal and smooth muscle fibers. Wall of the stomach, and intestine is formed by smooth muscle fibers., Smooth muscle fibers in stomach are arranged in, three layers:, i. Inner oblique layer, ii. Middle circular layer, iii. Outer longitudinal layer., Smooth muscle fibers in the intestine are arranged, in two layers:, i. Inner circular layer, ii. Outer longitudinal layer., Auerbach nerve plexus is present in between the, circular and longitudinal muscle fibers. The smooth, muscle fibers present in inner circular layer of anal, canal constitute internal anal sphincter. The external, anal sphincter is formed by skeletal muscle fibers.
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Chapter 36 t Introduction to Digestive System 221, 4. SEROUS OR FIBROUS LAYER, Outermost layer of the wall of GI tract is either serous or, fibrous in nature. The serous layer is also called serosa, or serous membrane and it is formed by connective, tissue and mesoepithelial cells. It covers stomach, small, intestine and large intestine., The fibrous layer is otherwise called fibrosa and it, is formed by connective tissue. It covers pharynx and, esophagus., , NERVE SUPPLY TO, GASTROINTESTINAL TRACT, GI tract has two types of nerve supply:, I. Intrinsic nerve supply, II. Extrinsic nerve supply., INTRINSIC NERVE SUPPLY –, ENTERIC NERVOUS SYSTEM, Intrinsic nerves to GI tract form the enteric nervous, system that controls all the secretions and movements, of GI tract. Enteric nervous system is present within the, wall of GI tract from esophagus to anus. Nerve fibers, of this system are interconnected and form two major, networks called, 1. Auerbach plexus, 2. Meissner plexus., These nerve plexus contain nerve cell bodies,, processes of nerve cells and the receptors. The receptors in the GI tract are stretch receptors and chemoreceptors. Enteric nervous system is controlled by, extrinsic nerves., 1. Auerbach Plexus, Auerbach plexus is also known as myenteric nerve, plexus. It is present in between the inner circular muscle, layer and the outer longitudinal muscle layer (Fig. 36.2)., Functions of Auerbach plexus, Major function of this plexus is to regulate the movements of GI tract. Some nerve fibers of this plexus, accelerate the movements by secreting the excitatory, neurotransmitter substances like acetylcholine, serotonin and substance P. Other fibers of this plexus, inhibit the GI motility by secreting the inhibitory neurotransmitters such as vasoactive intestinal polypeptide, (VIP), neurotensin and enkephalin., 2. Meissner Nerve Plexus, Meissner plexus is otherwise called submucus nerve, plexus. It is situated in between the muscular layer and, submucosal layer of GI tract., , FIGURE 36.2: Structure of intestinal wall with, intrinsic nerve plexus, , Functions of Meissner plexus, Function of Meissner plexus is the regulation of, secretory functions of GI tract. These nerve fibers cause, constriction of blood vessels of GI tract., EXTRINSIC NERVE SUPPLY, Extrinsic nerves that control the enteric nervous system, are from autonomic nervous system. Both sympathetic, and parasympathetic divisions of autonomic nervous, system innervate the GI tract (Fig. 36.3)., Sympathetic Nerve Fibers, Preganglionic sympathetic nerve fibers to GI tract arise, from lateral horns of spinal cord between fifth thoracic, and second lumbar segments (T5 to L2). From here, the, fibers leave the spinal cord, pass through the ganglia of, sympathetic chain without having any synapse and then, terminate in the celiac and mesenteric ganglia. The, postganglionic fibers from these ganglia are distributed, throughout the GI tract., Functions of sympathetic nerve fibers, Sympathetic nerve fibers inhibit the movements, and decrease the secretions of GI tract by secreting, the neurotransmitter noradrenaline. It also causes, constriction of sphincters., Parasympathetic Nerve Fibers, Parasympathetic nerve fibers to GI tract pass through, some of the cranial nerves and sacral nerves. The preganglionic and postganglionic parasympathetic nerve, fibers to mouth and salivary glands pass through facial, and glossopharyngeal nerves.
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222 Section 4 t Digestive System, , FIGURE 36.3: Extrinsic nerve supply to GI tract., T5 = 5th thoracic segment of spinal cord, L1 = 1st lumbar segment of spinal cord, S2 = 2nd sacral segment of spinal cord, , Preganglionic parasympathetic nerve fibers to esophagus, stomach, small intestine and upper part of large, intestine pass through vagus nerve. Preganglionic nerve, fibers to lower part of large intestine arise from second,, third and fourth sacral segments (S2, S3 and S4) of, spinal cord and pass through pelvic nerve. All these, preganglionic parasympathetic nerve fibers synapse, , with the postganglionic nerve cells in the myenteric and, submucus plexus., Functions of parasympathetic nerve fibers, Parasympathetic nerve fibers accelerate the movements and increase the secretions of GI tract. The, neurotransmitter secreted by the parasympathetic nerve, fibers is acetylcholine (Ach).
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Mouth and Salivary Glands, , , , , , , , , , Chapter, , 37, , FUNCTIONAL ANATOMY OF MOUTH, FUNCTIONS OF MOUTH, SALIVARY GLANDS, PROPERTIES AND COMPOSITION OF SALIVA, FUNCTIONS OF SALIVA, REGULATION OF SALIVARY SECRETION, EFFECT OF DRUGS AND CHEMICALS ON SALIVARY SECRETION, APPLIED PHYSIOLOGY, , FUNCTIONAL ANATOMY OF MOUTH, , MAJOR SALIVARY GLANDS, , Mouth is otherwise known as oral cavity or buccal, cavity. It is formed by cheeks, lips and palate. It encloses, , Major glands are:, 1. Parotid glands, 2. Submaxillary or submandibular glands, 3. Sublingual glands., , the teeth, tongue and salivary glands. Mouth opens, anteriorly to the exterior through lips and posteriorly, through fauces into the pharynx., Digestive juice present in the mouth is saliva, which, is secreted by the salivary glands., , FUNCTIONS OF MOUTH, Primary function of mouth is eating and it has few other, important functions also., Functions of mouth include:, 1. Ingestion of food materials, 2. Chewing the food and mixing it with saliva, 3. Appreciation of taste of the food, 4. Transfer of food (bolus) to the esophagus by, swallowing, 5. Role in speech, 6. Social functions such as smiling and other, expressions., , SALIVARY GLANDS, In humans, the saliva is secreted by three pairs of major, (larger) salivary glands and some minor (small) salivary, glands., , 1. Parotid Glands, Parotid glands are the largest of all salivary glands,, situated at the side of the face just below and in front of, the ear. Each gland weighs about 20 to 30 g in adults., Secretions from these glands are emptied into the oral, cavity by Stensen duct. This duct is about 35 mm to 40, mm long and opens inside the cheek against the upper, second molar tooth (Fig. 37.1)., 2. Submaxillary Glands, Submaxillary glands or submandibular glands are, located in submaxillary triangle, medial to mandible., Each gland weighs about 8 to 10 g. Saliva from these, glands is emptied into the oral cavity by Wharton duct,, which is about 40 mm long. The duct opens at the side, of frenulum of tongue, by means of a small opening on, the summit of papilla called caruncula sublingualis.
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224 Section 4 t Digestive System, TABLE 37.1: Ducts of major salivary glands, Gland, , Duct, , Parotid gland, , Stensen duct, , Submaxillary gland, , Wharton duct, , Sublingual gland, , Ducts of Rivinus/Bartholin duct, , 5. Palatal Glands, Palatal glands are found beneath the mucus membrane, of the soft palate., CLASSIFICATION OF SALIVARY GLANDS, Salivary glands are classified into three types, based on, the type of secretion:, 1. Serous Glands, FIGURE 37.1: Major salivary glands, , 3. Sublingual Glands, Sublingual glands are the smallest salivary glands, situated in the mucosa at the floor of the mouth. Each, gland weighs about 2 to 3 g. Saliva from these glands is, poured into 5 to 15 small ducts called ducts of Rivinus., These ducts open on small papillae beneath the tongue., One of the ducts is larger and it is called Bartholin duct, (Table 37.1). It drains the anterior part of the gland and, opens on caruncula sublingualis near the opening of, submaxillary duct., MINOR SALIVARY GLANDS, 1. Lingual Mucus Glands, Lingual mucus glands are situated in posterior one third, of the tongue, behind circumvallate papillae and at the, tip and margins of tongue., 2. Lingual Serous Glands, Lingual serous glands are located near circumvallate, papillae and filiform papillae., 3. Buccal Glands, Buccal glands or molar glands are present between, the mucus membrane and buccinator muscle. Four to, five of these are larger and situated outside buccinator,, around the terminal part of parotid duct., 4. Labial Glands, Labial glands are situated beneath the mucus membrane, around the orifice of mouth., , Serous glands are mainly made up of serous cells. These, glands secrete thin and watery saliva. Parotid glands, and lingual serous glands are the serous glands., 2. Mucus Glands, Mucus glands are mainly made up of mucus cells., These glands secrete thick, viscous saliva with high, mucin content. Lingual mucus glands, buccal glands, and palatal glands belong to this type., 3. Mixed Glands, Mixed glands are made up of both serous and mucus, cells. Submandibular, sublingual and labial glands are, the mixed glands., STRUCTURE AND DUCT SYSTEM, OF SALIVARY GLANDS, Salivary glands are formed by acini or alveoli. Each, acinus is formed by a small group of cells which surround, a central globular cavity. Central cavity of each acinus, is continuous with the lumen of the duct. The fine duct, draining each acinus is called intercalated duct. Many, intercalated ducts join together to form intralobular duct., Few intralobular ducts join to form interlobular ducts,, which unite to form the main duct of the gland (Fig. 37.2)., A gland with this type of structure and duct system is, called racemose type (racemose = bunch of grapes)., , PROPERTIES AND COMPOSITION, OF SALIVA, PROPERTIES OF SALIVA, 1. Volume: 1000 mL to 1500 mL of saliva is secreted, per day and it is approximately about 1 mL/minute.
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Chapter 37 t Mouth and Salivary Glands 225, 2. Reaction: Mixed saliva from all the glands is slightly, acidic with pH of 6.35 to 6.85, 3. Specific gravity: It ranges between 1.002 and 1.012, 4. Tonicity: Saliva is hypotonic to plasma., COMPOSITION OF SALIVA, Mixed saliva contains 99.5% water and 0.5% solids., Composition of saliva is given in Figure 37.3., , FUNCTIONS OF SALIVA, Saliva is a very essential digestive juice. Since it has many, functions, its absence leads to many inconveniences., 1. PREPARATION OF FOOD FOR SWALLOWING, , FIGURE 37.2: Diagram showing acini and duct system, in salivary glands, , Contribution by each major salivary gland is:, i. Parotid glands, : 25%, ii. Submaxillary glands : 70%, iii. Sublingual glands, : 5%., , When food is taken into the mouth, it is moistened and, dissolved by saliva. The mucus membrane of mouth is, also moistened by saliva. It facilitates chewing. By the, movement of tongue, the moistened and masticated, food is rolled into a bolus. Mucin of saliva lubricates the, bolus and facilitates swallowing., 2. APPRECIATION OF TASTE, Taste is a chemical sensation. By its solvent action,, saliva dissolves the solid food substances, so that the, , FIGURE 37.3: Composition of saliva
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226 Section 4 t Digestive System, dissolved substances can stimulate the taste buds. The, stimulated taste buds recognize the taste., 3. DIGESTIVE FUNCTION, Saliva has three digestive enzymes, namely salivary, amylase, maltase and lingual lipase (Table 37.1)., Salivary Amylase, Salivary amylase is a carbohydrate-digesting (amylolytic), enzyme. It acts on cooked or boiled starch and converts, it into dextrin and maltose. Though starch digestion, starts in the mouth, major part of it occurs in stomach, because, food stays only for a short time in the mouth., Optimum pH necessary for the activation of salivary, amylase is 6. Salivary amylase cannot act on cellulose., Maltase, Maltase is present only in traces in human saliva and it, converts maltose into glucose., Lingual Lipase, Lingual lipase is a lipid-digesting (lipolytic) enzyme. It, is secreted from serous glands situated on the posterior, aspect of tongue. It digests milk fats (pre-emulsified, fats). It hydrolyzes triglycerides into fatty acids and, diacylglycerol (Table 37.2)., 4. CLEANSING AND PROTECTIVE FUNCTIONS, i. Due to the constant secretion of saliva, the, mouth and teeth are rinsed and kept free off, food debris, shed epithelial cells and foreign, particles. In this way, saliva prevents bacterial, growth by removing materials, which may serve, as culture media for the bacterial growth., ii. Enzyme lysozyme of saliva kills some bacteria, such as staphylococcus, streptococcus and, brucella., iii. Proline-rich proteins present in saliva posses, antimicrobial property and neutralize the toxic, substances such as tannins. Tannins are present, in many food substances including fruits., , iv. Lactoferrin of saliva also has antimicrobial, property., v. Proline-rich proteins and lactoferrin protect the, teeth by stimulating enamel formation., vi. Immunoglobulin IgA in saliva also has, antibacterial and antiviral actions., vii. Mucin present in the saliva protects the mouth, by lubricating the mucus membrane of mouth., ROLE IN SPEECH, By moistening and lubricating soft parts of mouth and, lips, saliva helps in speech. If the mouth becomes dry,, articulation and pronunciation becomes difficult., EXCRETORY FUNCTION, Many substances, both organic and inorganic, are, excreted in saliva. It excretes substances like mercury,, potassium iodide, lead, and thiocyanate. Saliva also, excretes some viruses such as those causing rabies, and mumps., In some pathological conditions, saliva excretes, certain substances, which are not found in saliva under, normal conditions. Example is glucose in diabetes, mellitus. In certain conditions, some of the normal, constituents of saliva are excreted in large quantities., For example, excess urea is excreted in saliva during, nephritis and excess calcium is excreted during, hyperparathyroidism., REGULATION OF BODY TEMPERATURE, In dogs and cattle, excessive dripping of saliva during, panting helps in the loss of heat and regulation of body, temperature. However, in human beings, sweat glands, play a major role in temperature regulation and saliva, does not play any role in this function., REGULATION OF WATER BALANCE, When the body water content decreases, salivary secretion also decreases. This causes dryness of the mouth, and induces thirst. When water is taken, it quenches the, thirst and restores the body water content., , TABLE 37.2: Digestive enzymes of saliva, Enzyme, , Source of secretion, , Activator, , Action, , Salivary amylase, , All salivary glands, , Acid medium, , Converts starch into maltose, , Maltase, , Major salivary glands, , Acid medium, , Converts maltose into glucose, , Lingual lipase, , Lingual glands, , Acid medium, , Converts triglycerides of milk fat into fatty, acids and diacylglycerol
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Chapter 37 t Mouth and Salivary Glands 227, , REGULATION OF SALIVARY SECRETION, , NERVE SUPPLY TO SALIVARY GLANDS, , pass through the tympanic branch of glossopharyngeal, nerve, tympanic plexus and lesser petrosal nerve and, end in otic ganglion (Fig. 37.5)., Postganglionic fibers arise from this ganglion and, supply the parotid gland by passing through auriculotemporal branch in mandibular division of trigeminal, nerve., , Salivary glands are supplied by both parasympathetic, and sympathetic divisions of autonomic nervous system., , Function of Parasympathetic Fibers, , Salivary secretion is regulated only by nervous mechanism. Autonomic nervous system is involved in the, regulation of salivary secretion., , PARASYMPATHETIC FIBERS, Parasympathetic Fibers to Submandibular, and Sublingual Glands, Parasympathetic preganglionic fibers to submandibular, and sublingual glands arise from the superior salivatory, nucleus, situated in pons. After taking origin from this, nucleus, the preganglionic fibers run through nervus, intermedius of Wrisberg, geniculate ganglion, the motor, fibers of facial nerve, chorda tympani branch of facial, nerve and lingual branch of trigeminal nerve and finally, reach the submaxillary ganglion (Fig. 37.4)., Postganglionic fibers arising from this ganglion, supply the submaxillary and sublingual glands., , Stimulation of parasympathetic fibers of salivary glands, causes secretion of saliva with large quantity of water., It is because the parasympathetic fibers activate the, acinar cells and dilate the blood vessels of salivary, glands. However, the amount of organic constituents in, saliva is less. The neurotransmitter is acetylcholine., SYMPATHETIC FIBERS, Sympathetic preganglionic fibers to salivary glands, arise from the lateral horns of first and second thoracic, segments of spinal cord. The fibers leave the cord, through the anterior nerve roots and end in superior, cervical ganglion of the sympathetic chain., Postganglionic fibers arise from this ganglion and, are distributed to the salivary glands along the nerve, plexus, around the arteries supplying the glands., , Parasympathetic Fibers to Parotid Gland, Parasympathetic preganglionic fibers to parotid gland, arise from inferior salivatory nucleus situated in the, upper part of medulla oblongata. From here, the fibers, , Function of Sympathetic Fibers, Stimulation of sympathetic fibers causes secretion of, saliva, which is thick and rich in organic constituents such, , FIGURE 37.4: Parasympathetic nerve supply to submaxillary and sublingual glands
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228 Section 4 t Digestive System, , EFFECT OF DRUGS AND CHEMICALS, ON SALIVARY SECRETION, Substances which increase salivary secretion, 1. Sympathomimetic drugs like adrenaline and, ephedrine., 2. Parasympathomimetic drugs like acetylcholine,, pilocarpine, muscarine and physostigmine., 3. Histamine., Substances which decrease salivary secretion, 1. Sympathetic depressants like ergotamine and, dibenamine., 2. Parasympathetic depressants like atropine and, scopolamine., 3. Anesthetics such as chloroform and ether stimulate, the secretion of saliva. However, deep anesthesia, decreases the secretion due to central inhibition., , APPLIED PHYSIOLOGY, FIGURE 37.5: Parasympathetic nerve supply to parotid gland, , as mucus. It is because, these fibers activate the acinar, cells and cause vasoconstriction. The neurotransmitter, is noradrenaline., REFLEX REGULATION OF, SALIVARY SECRETION, Salivary secretion is regulated by nervous mechanism, through reflex action., Salivary reflexes are of two types:, 1. Unconditioned reflex., 2. Conditioned reflex., 1. Unconditioned Reflex, Unconditioned reflex is the inborn reflex that is present, since birth. It does not need any previous experience, (Chapter 162). This reflex induces salivary secretion, when any substance is placed in the mouth. It is due to, the stimulation of nerve endings in the mucus membrane, of the oral cavity., 2. Conditioned Reflex, Conditioned reflex is the one that is acquired by, experience and it needs previous experience (Chapter, 162). Presence of food in the mouth is not necessary to, elicit this reflex. The stimuli for this reflex are the sight,, smell, hearing or thought of food., , HYPOSALIVATION, Reduction in the secretion of saliva is called, hyposalivation. It is of two types, namely temporary, hyposalivation and permanent hyposalivation., 1. Temporary hyposalivation occurs in:, i. Emotional conditions like fear., ii. Fever., iii. Dehydration., 2. Permanent hyposalivation occurs in:, i. Sialolithiasis (obstruction of salivary duct)., ii. Congenital absence or hypoplasia of salivary, glands., iii. Bell palsy (paralysis of facial nerve)., HYPERSALIVATION, Excess secretion of saliva is known as hypersalivation., Physiological condition when hypersalivation occurs is, pregnancy. Hypersalivation in pathological conditions is, called ptyalism, sialorrhea, sialism or sialosis., Hypersalivation occurs in the following pathological, conditions:, 1. Decay of tooth or neoplasm (abnormal new growth, or tumor) in mouth or tongue due to continuous, irritation of nerve endings in the mouth., 2. Disease of esophagus, stomach and intestine., 3. Neurological disorders such as cerebral palsy, mental, retardation, cerebral stroke and parkinsonism., 4. Some psychological and psychiatric conditions., 5. Nausea and vomiting.
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Chapter 37 t Mouth and Salivary Glands 229, OTHER DISORDERS, In addition to hyposalivation and hypersalivation,, salivary secretion is affected by other disorders also,, which include:, 1. Xerostomia, 2. Drooling, 3. Chorda tympani syndrome, 4. Paralytic secretion of saliva, 5. Augmented secretion of saliva, 6. Mumps, 7. Sjögren syndrome., 1. Xerostomia, Xerostomia means dry mouth. It is also called pasties or, cottonmouth. It is due to hyposalivation or absence of, salivary secretion (aptyalism)., Causes, i., ii., iii., iv., v., , Dehydration or renal failure., Sjögren syndrome (see below)., Radiotherapy., Trauma to salivary gland or their ducts., Side effect of some drugs like antihistamines,, antidepressants, monoamine oxidase inhibitors,, antiparkinsonian drugs and antimuscarinic drugs., vi. Shock., vii. After smoking marijuana (psychoactive compound from the plant Cannabis)., Xerostomia causes difficulties in mastication, swa, llowing and speech. It also causes halitosis (bad breath;, exhalation of unpleasant odors)., 2. Drooling, Uncontrolled flow of saliva outside the mouth is called, drooling. It is often called ptyalism., Causes, Drooling occurs because of excess production of saliva, in, association with inability to retain saliva within the mouth., Drooling occurs in the following conditions:, i. During teeth eruption in children., ii. Upper respiratory tract infection or nasal allergies, in children., iii. Difficulty in swallowing., iv. Tonsillitis., v. Peritonsillar abscess., 3. Chorda Tympani Syndrome, Chorda tympani syndrome is the condition characterized, by sweating while eating. During trauma or surgical, , procedure, some of the parasympathetic nerve fibers to, salivary glands may be severed. During the regeneration,, some of these nerve fibers, which run along with chorda, tympani branch of facial nerve may deviate and join with, the nerve fibers supplying sweat glands. When the food, is placed in the mouth, salivary secretion is associated, with sweat secretion., 4. Paralytic Secretion of Saliva, When the parasympathetic nerve to salivary gland, is cut in experimental animals, salivary secretion, increases for first three weeks and later diminishes;, finally it stops at about sixth week. The increased, secretion of saliva after cutting the parasympathetic, nerve fibers is called paralytic secretion. It is because, of hyperactivity of sympathetic nerve fibers to salivary, glands after cutting the parasympathetic fibers. These, hyperactive sympathetic fibers release large amount, of catecholamines, which induce paralytic secretion., Moreover, the acinar cells of the salivary glands become, hypersensitive to catecholamines after denervation. The, paralytic secretion does not occur after the sympathetic, nerve fibers to salivary glands are cut., 5. Augmented Secretion of Saliva, If the nerves supplying salivary glands are stimulated, twice, the amount of saliva secreted by the second, stimulus is more than the amount secreted by the first, stimulus. It is because, the first stimulus increases, excitability of acinar cells, so that when the second stimulus, is applied, the salivary secretion is augmented., 6. Mumps, Mumps is the acute viral infection affecting the parotid, glands. The virus causing this disease is paramyxovirus., It is common in children who are not immunized. It, occurs in adults also. Features of mumps are puffiness, of cheeks (due to swelling of parotid glands), fever, sore, throat and weakness. Mumps affects meninges, gonads, and pancreas also., 7. Sjögren Syndrome, Sjögren syndrome is an autoimmune disorder in which, the immune cells destroy exocrine glands such as, lacrimal glands and salivary glands. It is named after, Henrik Sjögren who discovered it. Common symptoms, of this syndrome are dryness of the mouth due to lack, of saliva (xerostomia), persistent cough and dryness of, eyes. In some cases, it causes dryness of skin, nose and, vagina. In severe conditions, the organs like kidneys,, lungs, liver, pancreas, thyroid, blood vessels and brain, are affected.
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Chapter, , Stomach, , , , , , , , , , , , 38, , FUNCTIONAL ANATOMY OF STOMACH, GLANDS OF STOMACH – GASTRIC GLANDS, FUNCTIONS OF STOMACH, PROPERTIES AND COMPOSITION OF GASTRIC JUICE, FUNCTIONS OF GASTRIC JUICE, SECRETION OF GASTRIC JUICE, REGULATION OF GASTRIC SECRETION, COLLECTION OF GASTRIC JUICE, GASTRIC ANALYSIS, APPLIED PHYSIOLOGY, , FUNCTIONAL ANATOMY OF STOMACH, , 3. Body or Corpus, , Stomach is a hollow organ situated just below the, diaphragm on the left side in the abdominal cavity., Volume of empty stomach is 50 mL. Under normal, conditions, it can expand to accommodate 1 L to 1.5 L of, solids and liquids. However, it is capable of expanding, still further up to 4 L., , Body is the largest part of stomach forming about 75%, to 80% of the whole stomach. It extends from just below, the fundus up to the pyloric region (Fig. 38.1)., , PARTS OF STOMACH, In humans, stomach has four parts:, 1. Cardiac region, 2. Fundus, 3. Body or corpus, 4. Pyloric region., 1. Cardiac Region, Cardiac region is the upper part of the stomach where, esophagus opens. The opening is guarded by a sphinc, ter called cardiac sphincter, which opens only towards, stomach. This portion is also known as cardiac end., 2. Fundus, Fundus is a small domeshaped structure. It is elevated, above the level of esophageal opening., , 4. Pyloric Region, Pyloric region has two parts, antrum and pyloric canal., The body of stomach ends in antrum. Junction between, body and antrum is marked by an angular notch called, incisura angularis. Antrum is continued as the narrow, canal, which is called pyloric canal or pyloric end. Pyloric, canal opens into first part of small intestine called duo, denum. The opening of pyloric canal is guarded by a sphin, cter called pyloric sphincter. It opens towards duodenum., Stomach has two curvatures. One on the right side, is lesser curvature and the other on left side is greater, curvature., , STRUCTURE OF STOMACH WALL, Stomach wall is formed by four layers of structures:, 1. Outer serous layer: Formed by peritoneum, 2. Muscular layer: Made up of three layers of smooth, muscle fibers, namely inner oblique, middle circular, and outer longitudinal layers
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Chapter 38 t Stomach 231, STRUCTURE OF GASTRIC GLANDS, 1. Fundic Glands, Fundic glands are considered as the typical gastric, glands (Fig. 38.2). These glands are long and tubular., Each gland has three parts, viz. body, neck and, isthmus., Cells of fundic glands, 1., 2., 3., 4., 5., , FIGURE 38.1: Parts of stomach, , 3. Submucus layer: Formed by areolar tissue, blood, vessels, lymph vessels and Meissner nerve plexus., 4. Inner mucus layer: Lined by mucussecreting, columnar epithelial cells. The gastric glands are, situated in this layer. Under resting conditions,, the mucosa of the stomach is thrown into many, folds. These folds are called rugae. The rugae, disappear when the stomach is distended after, meals. Throughout the inner mucus layer, small, depressions called gastric pits are present. Glands, of the stomach open into these pits. Inner surface of, mucus layer is covered by 2 mm thick mucus., , Chief cells or pepsinogen cells, Parietal cells or oxyntic cells, Mucus neck cells, Enterochromaffin (EC) cells or Kulchitsky cells, Enterochromaffinlike (ECL) cells., Parietal cells are different from other cells of the, gland because of the presence of canaliculi (singular, = canaliculus). Parietal cells empty their secretions into, the lumen of the gland through the canaliculi. But, other, cells empty their secretions directly into lumen of the, gland., 2. Pyloric Glands, Pyloric glands are short and tortuous in nature. These, glands are formed by G cells, mucus cells, EC cells and, ECL cells., 3. Cardiac Glands, Cardiac glands are also short and tortuous in structure,, with many mucus cells. EC cells, ECL cells and chief, cells are also present in the cardiac glands, , GLANDS OF STOMACH –, GASTRIC GLANDS, Glands of the stomach or gastric glands are tubular, structures made up of different types of cells. These, glands open into the stomach cavity via gastric pits., CLASSIFICATION OF GLANDS, OF THE STOMACH, Gastric glands are classified into three types, on the, basis of their location in the stomach:, 1. Fundic glands or main gastric glands or oxyntic, glands: Situated in body and fundus of stomach, 2. Pyloric glands: Present in the pyloric part of the, stomach, 3. Cardiac glands: Located in the cardiac region of the, stomach., , FIGURE 38.2: Gastric glands
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232 Section 4 t Digestive System, Enteroendocrine Cells, , 4. HEMOPOIETIC FUNCTION, , Enteroendocrine cells are the hormonesecreting cells, present in the glands or mucosa of gastrointestinal tract,, particularly stomach and intestine. The enteroendocrine, cells present in gastric glands are G cells, EC cells and, ECL cells (Table 38.1)., , Refer functions of gastric juice., , FUNCTIONS OF GASTRIC GLANDS, , PROPERTIES AND COMPOSITION, OF GASTRIC JUICE, , Function of the gastric gland is to secrete gastric juice., Secretory activities of different cells of gastric glands, and enteroendocrine cells are listed in Table 38.1., , 5. EXCRETORY FUNCTION, Many substances like toxins, alkaloids and metals are, excreted through gastric juice., , Gastric juice is a mixture of secretions from different, gastric glands., , FUNCTIONS OF STOMACH, , PROPERTIES OF GASTRIC JUICE, , 1. MECHANICAL FUNCTION, , Volume, Reaction, , i. Storage Function, Food is stored in the stomach for a long period, i.e., for 3 to 4 hours and emptied into the intestine slowly., The maximum capacity of stomach is up to 1.5 L. Slow, emptying of stomach provides enough time for proper, digestion and absorption of food substances in the small, intestine., ii. Formation of Chyme, Peristaltic movements of stomach mix the bolus with, gastric juice and convert it into the semisolid material, known as chyme., 2. DIGESTIVE FUNCTION, , : 1200 mL/day to 1500 mL/day., : Gastric juice is highly acidic with a pH, of 0.9 to 1.2. Acidity of gastric juice is, due to the presence of hydrochloric, acid., Specific gravity : 1.002 to 1.004, COMPOSITION OF GASTRIC JUICE, Gastric juice contains 99.5% of water and 0.5% solids., Solids are organic and inorganic substances. Refer Fig., 38.3 for composition of gastric juice., , FUNCTIONS OF GASTRIC JUICE, 1. DIGESTIVE FUNCTION, , 3. PROTECTIVE FUNCTION, , Gastric juice acts mainly on proteins. Proteolytic enzymes, of the gastric juice are pepsin and rennin (Table 38.2)., Gastric juice also contains some other enzymes like, gastric lipase, gelatinase, urase and gastric amylase., , Refer functions of gastric juice., , Pepsin, , Refer functions of gastric juice., , TABLE 38.1: Secretory function of cells in gastric glands, Cell, , Chief cells, , Secretory products, Pepsinogen, Rennin, Lipase, Gelatinase, Urase, , Parietal cells, , Hydrochloric acid, Intrinsic factor of Castle, , Mucus neck cells, , Mucin, , G cells, , Gastrin, , Enterochromaffin (EC) cells, , Serotonin, , Enterochromaffinlike (ECL) cells Histamine, , Pepsin is secreted as inactive pepsinogen. Pepsinogen, is converted into pepsin by hydrochloric acid. Optimum, pH for activation of pepsinogen is below 6., Action of pepsin, Pepsin converts proteins into proteoses, peptones and, polypeptides. Pepsin also causes curdling and digestion, of milk (casein)., Gastric Lipase, Gastric lipase is a weak lipolytic enzyme when compared, to pancreatic lipase. It is active only when the pH is, between 4 and 5 and becomes inactive at a pH below
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Chapter 38 t Stomach 233, 2.5. Gastric lipase is a tributyrase and it hydrolyzes, tributyrin (butter fat) into fatty acids and glycerols., Actions of Other Enzymes of Gastric Juice, i. Gelatinase: Degrades type I and type V gelatin, and type IV and V collagen (which are proteo, glycans in meat) into peptides, ii. Urase: Acts on urea and produces ammonia, iii. Gastric amylase: Degrades starch (but its action, is insignificant), iv. Rennin: Curdles milk (present in animals only)., , Vitamin B12 is an important maturation factor during, erythropoiesis. Absence of intrinsic factor in gastric, juice causes deficiency of vitamin B12, leading to, pernicious anemia (Chapter 14)., PROTECTIVE FUNCTION –, FUNCTION OF MUCUS, Mucus is a mucoprotein, secreted by mucus neck cells, of the gastric glands and surface mucus cells in fundus,, body and other parts of stomach. It protects the gastric, wall by the following ways:, Mucus:, , 2. HEMOPOIETIC FUNCTION, Intrinsic factor of Castle, secreted by parietal cells of, gastric glands plays an important role in erythropoiesis., It is necessary for the absorption of vitamin B12 (which, is called extrinsic factor) from GI tract into the blood., , i. Protects the stomach wall from irritation or, mechanical injury, by virtue of its high viscosity., ii. Prevents the digestive action of pepsin on the, wall of the stomach, particularly gastric mucosa., , FIGURE 38.3: Composition of gastric juice, , TABLE 38.2: Digestive enzymes of gastric juice, Enzyme, , Activator, , Substrate, , End products, , Pepsin, , Hydrochloric acid, , Proteins, , Proteoses, peptones and polypeptides, , Gastric lipase, , Acid medium, , Triglycerides of butter, , Fatty acids and glycerols, , Gastric amylase, , Acid medium, , Starch, , Dextrin and maltose (negligible action), , Gelatinase, , Acid medium, , Gelatin and collagen of meat, , Peptides, , Urase, , Acid medium, , Urea, , Ammonia
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234 Section 4 t Digestive System, iii. Protects the gastric mucosa from hydrochloric, acid of gastric juice because of its alkaline, nature and its acidcombining power., 4. FUNCTIONS OF HYDROCHLORIC ACID, Hydrochloric acid is present in the gastric juice:, i. Activates pepsinogen into pepsin, ii. Kills some of the bacteria entering the stomach, along with food substances. This action is called, bacteriolytic action, iii. Provides acid medium, which is necessary for, the action of hormones., , SECRETION OF GASTRIC JUICE, SECRETION OF PEPSINOGEN, , Factors Stimulating the Secretion, of Hydrochloric Acid, 1. Gastrin, 2. Histamine, 3. Vagal stimulation., Factors Inhibiting the Secretion, of Hydrochloric Acid, 1. Secretin, 2. Gastric inhibitory polypeptide, 3. Peptide YY., , REGULATION OF GASTRIC SECRETION, Regulation of gastric secretion and intestinal secretion, is studied by some experimental procedures., , Pepsinogen is synthesized from amino acids in the, ribosomes attached to endoplasmic reticulum in chief, cells. Pepsinogen molecules are packed into zymogen, granules by Golgi apparatus., When zymogen granule is secreted into stomach, from chief cells, the granule is dissolved and pepsinogen, is released into gastric juice. Pepsinogen is activated, into pepsin by hydrochloric acid., , METHODS OF STUDY, , SECRETION OF HYDROCHLORIC ACID, , Procedure, , According to Davenport theory, hydrochloric acid, secretion is an active process that takes place in the, canaliculi of parietal cells in gastric glands. The energy, for this process is derived from oxidation of glucose., Carbon dioxide is derived from metabolic activities, of parietal cell. Some amount of carbon dioxide is, obtained from blood also. It combines with water to form, carbonic acid in the presence of carbonic anhydrase., This enzyme is present in high concentration in parietal, cells. Carbonic acid is the most unstable compound and, immediately splits into hydrogen ion and bicarbonate, ion. The hydrogen ion is actively pumped into the, canaliculus of parietal cell., Simultaneously, the chloride ion is also pumped, into canaliculus actively. The chloride is derived from, sodium chloride in the blood. Now, the hydrogen ion, combines with chloride ion to form hydrochloric acid. To, compensate the loss of chloride ion, the bicarbonate ion, from parietal cell enters the blood and combines with, sodium to form sodium bicarbonate. Thus, the entire, process is summarized as (Fig. 38.4):, CO2 + H2O + NaCl → HCl + NaHCO3, , To prepare a Pavlov pouch, stomach of an anesthetized, dog is divided into a larger part and a smaller part by, making an incomplete incision. The mucus membrane, , 1. Pavlov Pouch, Pavlov pouch is a small part of the stomach that is, incompletely separated from the main portion and made, into a small baglike pouch (Fig. 38.5). Pavlov pouch, was designed by the Russian scientist Pavlov, in a dog, during his studies on conditioned reflexes., , FIGURE 38.4: Secretion of hydrochloric acid in the, parietal cell of gastric gland
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Chapter 38 t Stomach 235, is completely divided. A small part of muscular coat, called isthmus is retained. Isthmus connects the two, parts., The cut edges of major portions are stitched. Smaller, part is also stitched, leaving a small outlet. This outlet, is brought out through the abdominal wall and used to, drain the pouch., Nerve supply of Pavlov pouch, Pavlov pouch receives parasympathetic (vagus) nerve, fibers through isthmus and sympathetic fibers through, blood vessels., Use of Pavlov pouch, Pavlov pouch is used to demonstrate the different, phases of gastric secretion, particularly the cephalic, phase and used to demonstrate the role of vagus in, cephalic phase., 2. Heidenhain Pouch, Heidenhain pouch is the modified Pavlov pouch. It is, completely separated from main portion of stomach by, cutting the isthmus without damaging blood vessels. So,, the blood vessels are intact. Thus, Heidenhain pouch, does not have parasympathetic supply, but the sym, pathetic fibers remain intact through the blood vessels., Uses of Heidenhain pouch, Heidenhain pouch is useful to demonstrate the role of, sympathetic nerve and the hormonal regulation of gastric, secretion after vagotomy (cutting the vagus nerve)., , 3. Bickel Pouch, In this, even the sympathetic nerve fibers are cut by, removing the blood vessels. So, Bickel pouch is a totally, denervated pouch., Uses of Bickel pouch, Bickel pouch is used to demonstrate the role of hormones, in gastric secretion., 4. Farrel and Ivy Pouch, Farrel and Ivy pouch is prepared by completely removing, the Bickel pouch from the stomach and transplanting it, in the subcutaneous tissue of abdominal wall or thoracic, wall in the same animal. New blood vessels develop, after some days. It is used for experimental purpose,, when the new blood vessels are developed., Uses of Farrel and Ivy pouch, This pouch is useful to study the role of hormones during, gastric and intestinal phases of gastric secretion., 5. Sham Feeding, Sham feeding means the false feeding. It is another, experimental procedure devised by Pavlov to demons, trate the regulation of gastric secretion., Procedure, i. A hole is made in the neck of an anesthetized, dog, ii. Esophagus is transversely cut and the cut ends, are drawn out through the hole in the neck, iii. When the dog eats food, it comes out through, the cut end of the esophagus, iv. But the dog has the satisfaction of eating the, food. Hence it is called sham feeding., This experimental procedure is supported by the, preparation of Pavlov pouch with a fistula from the, stomach. The fistula opens to exterior and it is used to, observe the gastric secretion. The animal is used for, experimental purpose after a week, when healing is, completed., Advantage of sham feeding, Sham feeding is useful to demonstrate the secretion of, gastric juice during cephalic phase. In the same animal, after vagotomy, sham feeding does not induce gastric, secretion. It proves the role of vagus nerve during, cephalic phase., PHASES OF GASTRIC SECRETION, , FIGURE 38.5: Pavlov pouch, , Secretion of gastric juice is a continuous process. But, the quantity varies, depending upon time and stimulus.
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236 Section 4 t Digestive System, Accordingly, gastric secretion occurs in three different, phases:, I. Cephalic phase, II. Gastric phase, III. Intestinal phase., In human beings, a fourth phase called interdigestive, phase exists. Each phase is regulated by neural mechan, ism or hormonal mechanism or both., CEPHALIC PHASE, Secretion of gastric juice by the stimuli arising from, head region (cephalus) is called cephalic phase (Fig., 38.6). This phase of gastric secretion is regulated by, nervous mechanism. The gastric juice secreted during, this phase is called appetite juice., During this phase, gastric secretion occurs even, without the presence of food in stomach. The quantity of, the juice is less but it is rich in enzymes and hydrochloric, acid., , Nervous mechanism regulates cephalic phase, through reflex action. Two types of reflexes occur:, 1. Unconditioned reflex, 2. Conditioned reflex., 1. Unconditioned Reflex, Unconditioned reflex is the inborn reflex. When food, is placed in the mouth, salivary secretion is induced, (Chapter 37). Simultaneously, gastric secretion also, occurs., Stages of reflex action:, i. Presence of food in the mouth stimulates the, taste buds and other receptors in the mouth, ii. Sensory (afferent) impulses from mouth pass via, afferent nerve fibers of glossopharyngeal and, facial nerves to amygdala and appetite center, present in hypothalamus, , FIGURE 38.6: Schematic diagram showing the regulation of gastric secretion, CCKPZ = Cholecystokininpancreozymin, GIP = Gastric inhibitory peptide, VIP = Vasoactive intestinal peptide.
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Chapter 38 t Stomach 237, iii. From here, the efferent impulses pass through, dorsal nucleus of vagus and vagal efferent nerve, fibers to the wall of the stomach, iv. Vagal efferent nerve endings secrete acetylcho, line, which stimulates gastric secretion., 2. Conditioned Reflex, Conditioned reflex is the reflex response acquired by, previous experience (Chapter 162). Presence of food in, the mouth is not necessary to elicit this reflex. The sight,, smell, hearing or thought of food, which induce salivary, secretion induce gastric secretion also., Stages of reflex action:, i. Impulses from the special sensory organs (eye,, ear and nose) pass through afferent fibers of, neural circuits to the cerebral cortex. Thinking of, food stimulates the cerebral cortex directly, ii. From cerebral cortex, the impulses pass through, dorsal nucleus of vagus and vagal efferents and, reach the stomach wall, iii. Vagal nerve endings secrete acetylcholine,, which stimulates the gastric secretion., Experimental evidences to prove cephalic phase, i. Unconditioned reflex of gastric secretion is prov, ed by sham feeding along with Pavlov pouch, (see above). After vagotomy, sham feeding, does not cause gastric secretion. It proves the, importance of vagus nerve in this phase., ii. Conditioned reflex of gastric secretion is proved, by Pavlov pouch and belldog experiment, (Chapter 162)., GASTRIC PHASE, Secretion of gastric juice when food enters the stomach, is called gastric phase. This phase is regulated by both, nervous and hormonal control. Gastric juice secreted, during this phase is rich in pepsinogen and hydrochloric, acid., Mechanisms involved in gastric phase are:, 1. Nervous mechanism through local myenteric reflex, and vagovagal reflex, 2. Hormonal mechanism through gastrin, Stimuli, which initiate these two mechanisms are:, 1. Distention of stomach, 2. Mechanical stimulation of gastric mucosa by bulk of, food, 3. Chemical stimulation of gastric mucosa by the food, contents., , 1. Nervous Mechanism, Local myenteric reflex, Local myenteric reflex is the reflex elicited by stimulation, of myenteric nerve plexus in stomach wall. After, entering stomach, the food particles stimulate the local, nerve plexus (Chapter 36) present in the wall of the, stomach. These nerve fibers release acetylcholine,, which stimulates the gastric glands to secrete a large, quantity of gastric juice. Simultaneously, acetylcholine, stimulates G cells to secrete gastrin (see below)., Vagovagal reflex, Vagovagal reflex is the reflex which involves both afferent, and efferent vagal fibers. Entrance of bolus into the, stomach stimulates the sensory (afferent) nerve endings, of vagus and generates sensory impulses. These, sensory impulses are transmitted by sensory fibers of, vagus to dorsal nucleus of vagus, located in medulla of, brainstem. This nucleus in turn, sends efferent impulses, through the motor (efferent) fibers of vagus, back to, stomach and cause secretion of gastric juice. Since,, both afferent and efferent impulses pass through vagus,, this reflex is called vagovagal reflex (Fig. 38.7)., 2. Hormonal Mechanism – Gastrin, Gastrin is a gastrointestinal hormone secreted by the G, cells which are present in the pyloric glands of stomach., Small amount of gastrin is also secreted in mucosa of, upper small intestine. In fetus, it is also secreted by islets, of Langerhans in pancreas. Gastrin is a polypeptide, containing G14, G17 or G34 amino acids., Gastrin is released when food enters stomach., Mechanism involved in the release of gastrin may be the, local nervous reflex or vagovagal reflex. Nerve endings, release the neurotransmitter called gastrinreleasing, peptide, which stimulates the G cells to secrete gastrin., Actions of gastrin on gastric secretion, Gastrin stimulates the secretion of pepsinogen and, hydrochloric acid by the gastric glands. Refer Chapter, 44 for other actions of gastrin., Experimental evidences of gastric phase, Nervous mechanism of gastric secretion during gastric, phase is proved by Pavlov pouch. Hormonal mechanism, of gastric secretion is proved by Heidenhain pouch,, Bickel pouch and Farrel and Ivy pouch., INTESTINAL PHASE, Intestinal phase is the secretion of gastric juice when, chyme enters the intestine. When chyme enters the
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238 Section 4 t Digestive System, , FIGURE 38.7: Vagovagal reflex, , intestine, initially, the gastric secretion increases but, later it stops. Intestinal phase of gastric secretion is, regulated by nervous and hormonal control., Initial Stage of Intestinal Phase, Chyme that enters the intestine stimulates the duodenal, mucosa to release gastrin, which is transported to, stomach by blood. There it increases gastric secretion., Later Stage of Intestinal Phase, After the initial increase, there is a decrease or complete, stoppage of gastric secretion. Gastric secretion is, inhibited by two factors:, 1. Enterogastric reflex, 2. Gastrointestinal (GI) hormones., 1. Enterogastric reflex, Enterogastric reflex inhibits the gastric secretion and, motility. It is due to the distention of intestinal mucosa, by chyme or chemical or osmotic irritation of intestinal, mucosa by chemical substances in the chyme. It is media, ted by myenteric nerve (Auerbach) plexus and vagus., , 2. Gastrointestinal hormones, Presence of chyme in the intestine stimulates the secre, tion of many GI hormones from intestinal mucosa and, other structures. All these hormones inhibit the gastric, secretion. Some of these hormones inhibit the gastric, motility also., GI hormones which inhibit gastric secretion:, i. Secretin: Secreted by the presence of acid, chyme in the intestine, ii. Cholecystokinin: Secreted by the presence, of chyme containing fats and amino acids in, intestine, iii. Gastric inhibitory peptide (GIP): Secreted by the, presence of chyme containing glucose and fats, in the intestine, iv. Vasoactive intestinal polypeptide (VIP): Secreted, by the presence of acidic chyme in intestine, v. Peptide YY: Secreted by the presence of fatty, chyme in intestine., In addition to these hormones, pancreas also, secretes a hormone called somatostatin during
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Chapter 38 t Stomach 239, intestinal phase. It also inhibits gastric secretion. Refer, Chapter 44 for details of GI hormones., Thus, enterogastric reflex and intestinal hormones, collectively apply a strong brake on the secretion and, motility of stomach during intestinal phase., , i. A piece of bread and a cup of tea, ii. Wheat biscuit and 400 mL of water, iii. 300 mL of oatmeal gruel., Fractional gastric analysis, , Intestinal phase of gastric secretion is demonstrated by, Bickel pouch and Farrel and Ivy pouch., , After the ingestion of a test meal, gastric juice is collected, at every 15th minute for a period of two and a half hours., All these samples are analyzed for peptic activity and, acidity., , INTERDIGESTIVE PHASE, , 2. Nocturnal Gastric Analysis, , Secretion of small amount of gastric juice in between, meals (or during period of fasting) is called interdigestive, phase. Gastric secretion during this phase is mainly, due to the hormones like gastrin. This phase of gastric, secretion is demonstrated by Farrel and Ivy pouch., , Patient is given a clear liquid diet at noon and at 5 pm., At 7.30 pm, the tube is introduced into the patients’s, stomach. Then from 8 pm to 8 am, hourly samples of, gastric juice are collected and analyzed., , Experimental evidences for intestinal phase, , 3. Histamine Test, FACTORS INFLUENCING GASTRIC SECRETION, Gastric secretion is also influenced by some factors, which increase the gastric secretion by stimulating, gastric mucosa such as:, 1. Alcohol, 2. Caffeine., , After overnight fasting, the stomach is emptied in the, morning by aspiration. Then histamine is injected, subcutaneously (0.01 mg/kg). Histamine stimulates, secretion of hydrochloric acid in the stomach. After 30, minutes, 4 samples of gastric juice are collected over a, period of 1 hour at 15 minutes interval and analyzed., , COLLECTION OF GASTRIC JUICE, , APPLIED PHYSIOLOGY, , In human beings, the gastric juice is collected by using, Ryle tube. The tube is made out of rubber or plastic. It is, passed through nostril or mouth and through esophagus, into the stomach. A line is marked in the tube. The, entrance of the tip of the tube into stomach is indicated, when this line comes near the mouth. Then, the contents, of stomach are collected by means of aspiration., , Gastric secretion is affected by the following disorders:, , GASTRIC ANALYSIS, For analysis, the gastric juice is collected from patient only, in the morning. Analysis of the gastric juice is done for the, diagnosis of ulcer and other disorders of stomach., Gastric juice is analyzed for the following:, 1. Measurement of peptic activity, 2. Measurement of gastric acidity: Total acid, free acid, (hydrochloric acid) and combined acid., METHODS OF GASTRIC ANALYSIS, 1. Fractional Test Meal (FTM), After overnight fasting, the gastric juice is collected., Then, the patient takes a small test meal called fractional, test meal (FTM)., Typical test meals are:, , 1. GASTRITIS, Inflammation of gastric mucosa is called gastritis. It may, be acute or chronic. Acute gastritis is characterized by, inflammation of superficial layers of mucus membrane, and infiltration with leukocytes, mostly neutrophils., Chronic gastritis involves inflammation of even the, deeper layers and infiltration with more lymphocytes. It, results in the atrophy of the gastric mucosa, with loss, of chief cells and parietal cells of glands. Therefore, the, secretion of gastric juice decreases., Causes of Acute Gastritis, i. Infection with bacterium Helicobacter pylori, ii. Excess consumption of alcohol, iii. Excess administration of Aspirin and other non, steroidal antiinflammatory drugs (NSAIDs), iv. Trauma by nasogastric tubes, v. Repeated exposure to radiation (rare)., Causes of Chronic Gastritis, i. Chronic infection with Helicobacter pylori
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240 Section 4 t Digestive System, ii. Longterm intake of excess alcohol, iii. Longterm use of NSAIDs, iv. Autoimmune disease., Features, Features of gastritis are nonspecific. Common feature, is abdominal upset or pain felt as a diffused burning, sensation. It is often referred to epigastric pain. Other, features are:, i. Nausea, ii. Vomiting, iii. Anorexia (loss of appetite), iv. Indigestion, v. Discomfort or feeling of fullness in the, epigastric region, vi. Belching (process to relieve swallowed air, that is accumulated in stomach)., 2. GASTRIC ATROPHY, Gastric atrophy is the condition in which the muscles of, the stomach shrink and become weak. Gastric glands, also shrink, resulting in the deficiency of gastric juice., Cause, , Causes, i. Increased peptic activity due to excessive, secretion of pepsin in gastric juice, ii. Hyperacidity of gastric juice, iii. Reduced alkalinity of duodenal content, iv. Decreased mucin content in gastric juice or, decreased protective activity in stomach or, duodenum, v. Constant physical or emotional stress, vi. Food with excess spices or smoking (classical, causes of ulcers), vii. Longterm use of NSAIDs (see above) such as, Aspirin, Ibuprofen and Naproxen, viii. Chronic inflammation due to Helicobacter pylori., Features, Most common feature of peptic ulcer is severe burning, pain in epigastric region. In gastric ulcer, pain occurs, while eating or drinking. In duodenal ulcer, pain is felt 1, or 2 hours after food intake and during night., Other symptoms accompanying pain are:, i. Nausea, ii. Vomiting, iii. Hematemesis (vomiting blood), iv. Heartburn (burning pain in chest due to regurgi, tation of acid from stomach into esophagus), v. Anorexia (loss of appetite), vi. Loss of weight., , Gastric atrophy is caused by chronic gastritis called, chronic atrophic gastritis. There is atrophy of gastric, mucosa including loss of gastric glands. Autoimmune, atrophic gastritis also causes gastric atrophy., , 4. ZOLLINGER-ELLISON SYNDROME, , Features, , ZollingerEllison syndrome is characterized by secretion, of excess hydrochloric acid in the stomach., , Generally, gastric atrophy does not cause any noticeable, symptom. However, it may lead to achlorhydria (absence, of hydrochloric acid in gastric juice) and pernicious, anemia. Some patients develop gastric cancer., 3. PEPTIC ULCER, Ulcer means the erosion of the surface of any organ due, to shedding or sloughing of inflamed necrotic tissue that, lines the organ. Peptic ulcer means an ulcer in the wall, of stomach or duodenum, caused by digestive action, of gastric juice. If peptic ulcer is found in stomach, it, is called gastric ulcer and if found in duodenum, it is, called duodenal ulcer., , Cause, This disorder is caused by tumor of pancreas. Pancreatic, tumor produces a large quantity of gastrin. Gastrin, increases the hydrochloric acid secretion in stomach by, stimulating the parietal cells of gastric glands., Features, i. Abdominal pain, ii. Diarrhea (frequent and watery, loose bowel, movements), iii. Difficulty in eating, iv. Occasional hematemesis (see above).
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Chapter, , Pancreas, , 39, , FUNCTIONAL ANATOMY AND NERVE SUPPLY OF PANCREAS, PROPERTIES AND COMPOSITION OF PANCREATIC JUICE, FUNCTIONS OF PANCREATIC JUICE, , , , , , , DIGESTIVE FUNCTIONS, DIGESTION OF PROTEINS, DIGESTION OF LIPIDS, DIGESTION OF CARBOHYDRATES, NEUTRALIZING ACTION, , MECHANISM OF PANCREATIC SECRETION, , , , SECRETION OF PANCREATIC ENZYMES, SECRETION OF BICARBONATE IONS, , REGULATION OF PANCREATIC SECRETION, , , , , , STAGES OF PANCREATIC SECRETION, CEPHALIC PHASE, GASTRIC PHASE, INTESTINAL PHASE, , COLLECTION OF PANCREATIC JUICE, , , , IN ANIMALS, IN HUMAN, , APPLIED PHYSIOLOGY, , , , PANCREATITIS, STEATORRHEA, , FUNCTIONAL ANATOMY AND, NERVE SUPPLY OF PANCREAS, Pancreas is a dual organ having two functions, namely, endocrine function and exocrine function. Endocrine, function is concerned with the production of hormones, (Chapter 69). The exocrine function is concerned with, the secretion of digestive juice called pancreatic juice., FUNCTIONAL ANATOMY OF EXOCRINE, PART OF PANCREAS, Exocrine part of pancreas resembles salivary gland in, structure. It is made up of acini or alveoli. Each acinus, , has a single layer of acinar cells with a lumen in the, center. Acinar cells contain zymogen granules, which, possess digestive enzymes., A small duct arises from lumen of each alveolus., Some of these ducts from neighboring alveoli unite to, form intralobular duct. All the intralobular ducts unite, to form the main duct of pancreas called Wirsung duct., Wirsung duct joins common bile duct to form ampulla of, Vater, which opens into duodenum (see Fig. 40.3)., In some persons, an accessory duct called duct of, Santorini exists. It also opens into duodenum, proximal, to the opening of ampulla of Vater.
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242 Section 4 t Digestive System, NERVE SUPPLY TO PANCREAS, Pancreas is supplied by both sympathetic and para, sympathetic fibers. Sympathetic fibers are supplied, through splanchnic nerve and parasympathetic fibers, are supplied through vagus nerve., , PROPERTIES AND COMPOSITION, OF PANCREATIC JUICE, , i. High bicarbonate content makes the pancreatic, juice highly alkaline, so that it protects the intes, tinal mucosa from acid chyme by neutralizing it, ii. Bicarbonate ions provide the required pH (7 to, 9) for the activation of pancreatic enzymes., , FUNCTIONS OF PANCREATIC JUICE, Pancreatic juice has digestive functions and neutralizing, action., , PROPERTIES OF PANCREATIC JUICE, Volume, : 500 to 800 mL/day, Reaction, : Highly alkaline with a pH of 8 to 8.3, Specific gravity : 1.010 to 1.018, COMPOSITION OF PANCREATIC JUICE, Pancreatic juice contains 99.5% of water and 0.5%, of solids. The solids are the organic and inorganic, substances. Composition of pancreatic juice is given in, Fig. 39.1., Bicarbonate content is very high in pancreatic juice., It is about 110 to 150 mEq/ L, against the plasma level of, 24 mEq/L. High bicarbonate content of pancreatic juice, is important because of two reasons:, , DIGESTIVE FUNCTIONS OF PANCREATIC JUICE, Pancreatic juice plays an important role in the digestion, of proteins and lipids. It also has mild digestive action, on carbohydrates., DIGESTION OF PROTEINS, Major proteolytic enzymes of pancreatic juice are trypsin, and chymotrypsin. Other proteolytic enzymes are carbo, xypeptidases, nuclease, elastase and collagenase., 1. Trypsin, Trypsin is a single polypeptide with a molecular weight, of 25,000. It contains 229 amino acids., , FIGURE 39.1: Composition of pancreatic juice
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244 Section 4 t Digestive System, acids. Activity of pancreatic lipase is accelerated in the, presence of bile. Optimum pH required for activity of this, enzyme is 7 to 9., Digestion of fat by pancreatic lipase requires two, more factors:, i. Bile salts, which are responsible for the emulsi, fication of fat, prior to their digestion, ii. Colipase, which is a coenzyme necessary for, the pancreatic lipase to digest the dietary lipids., About 80% of the fat is digested by pancreatic lipase., Deficiency or absence of this enzyme leads to excretion, of undigested fat in feces (steatorrhea; see below)., , NEUTRALIZING ACTION OF, PANCREATIC JUICE, When acid chyme enters intestine from stomach,, pancreatic juice with large quantity of bicarbonate is, released into intestine. Presence of large quantity of, bicarbonate ions makes the pancreatic juice highly, alkaline. This alkaline pancreatic juice neutralizes acidity, of chyme in the intestine., Neutralizing action is an important function of, pancreatic juice because it protects the intestine from, the destructive action of acid in the chyme., , 2. Cholesterol ester hydrolase, , MECHANISM OF, PANCREATIC SECRETION, , Cholesterol ester hydrolase or cholesterol esterase, converts cholesterol ester into free cholesterol and fatty, acid by hydrolysis., , SECRETION OF PANCREATIC ENZYMES, , 3. Phospholipase A, Phospholipase A is activated by trypsin. Phospholipase, A digests phospholipids, namely lecithin and cephalin, and converts them into lysophospholipids. It converts, lecithin into lysolecithin and cephalin into lysocephalin., 4. Phospholipase B, Phospholipase B is also activated by trypsin. It converts, lysophospholipids (lysolecithin and lysocephalin) to, phosphoryl choline and free fatty acids., 5. Colipase, Colipase is a small coenzyme, secreted as inactive, procolipase. Procolipase is activated into colipase by, trypsin. Colipase facilitates digestive action of pancreatic, lipase on fats., 6. Bile-salt-activated lipase, Bilesaltactivated lipase is the lipolytic enzyme activated, by bile salt. It is also called carboxyl ester lipase or, cholesterol esterase. This enzyme has a weak lipolytic, action than pancreatic lipase. But it hydrolyses a variety, of lipids such as phospholipids, cholesterol esters and, triglycerides. Human milk contains an enzyme similar to, bile-salt-activated lipase (Table 39.1)., DIGESTION OF CARBOHYDRATES, Pancreatic amylase is the amylolytic enzyme present in, pancreatic juice. Like salivary amylase, the pancreatic, amylase also converts starch into dextrin and maltose., , Pancreatic enzymes are synthesized in ribosomes,, which are attached to the endoplasmic reticulum of, acinar cells in pancreas. The raw materials for the, synthesis of pancreatic enzymes are the amino acids,, which are derived from the blood. After synthesis, the, enzymes are packed into different zymogen granules, by Golgi apparatus and stored in cytoplasm. When, stimulated, the acinar cells release zymogen granules, into the pancreatic duct. From the granules, the enzymes, are liberated into intestine., SECRETION OF BICARBONATE IONS, Bicarbonate ions of pancreatic juice are secreted from, the cells of pancreatic ductules and released into the, pancreatic duct., Mechanism of bicarbonate secretion, 1. Carbon dioxide derived from blood or metabolic, process combines with water inside the cell to, form carbonic acid in the presence of carbonic, anhydrase, 2. Carbonic acid dissociates into hydrogen and bicar, bonate ions, 3. Bicarbonate ions are actively transported out of the, cell into the lumen, 4. Hydrogen ion is actively transported into blood in, exchange for sodium ion, 5. Sodium ion from the cell is transported into the, lumen, where it combines with bicarbonate to form, sodium bicarbonate, 6. Because of the loss of sodium and bicarbonate, ions from the blood, there is some disturbance in, the osmotic equilibrium of the blood. To maintain
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Chapter 39 t Pancreas 245, TABLE 39.1: Digestive enzymes of pancreatic juice, Enzyme, , Activator, , Acts on (substrate), , End products, , Trypsin, , Enterokinase, Trypsin, , Proteins, , Proteoses and polypeptides, , Chymotrypsin, , Trypsin, , Proteins, , Polypeptides, , Carboxypeptidases, , Trypsin, , Polypeptides, , Amino acids, , Nucleases, , Trypsin, , RNA and DNA, , Mononucleotides, , Elastase, , Trypsin, , Elastin, , Amino acids, , Collagenase, , Trypsin, , Collagen, , Amino acids, , Pancreatic lipase, , Alkaline medium, , Triglycerides, , Monoglycerides and fatty acids, , Cholesterol ester hydrolase, , Alkaline medium, , Cholesterol ester, , Cholesterol and fatty acids, , Phospholipase A, , Trypsin, , Phospholipids, , Lysophospholipids, , Phospholipase B, , Trypsin, , Lysophospholipids, , Phosphoryl choline and free fatty acids, , Colipase, , Trypsin, , Facilitates action of, pancreatic lipase, , –, , Phospholipids, , Lysophospholipids, , Bilesaltactivated lipase, Pancreatic amylase, , Trypsin, –, , Cholesterol esters, , Cholesterol and fatty acids, , Triglycerides, , Monoglycerides and fatty acids, , Starch, , Dextrin and maltose, , the osmotic equilibrium, water leaves the blood and, enters the lumen of pancreatic duct by osmosis, 7. In the lumen, bicarbonate combines with water, forming the solution of bicarbonate., , REGULATION OF PANCREATIC, SECRETION, Secretion of pancreatic juice is regulated by both, nervous and hormonal factors., STAGES OF PANCREATIC SECRETION, Pancreatic juice is secreted in three stages (Fig. 39.2), like the gastric juice:, 1. Cephalic phase, 2. Gastric phase, 3. Intestinal phase., These three phases of pancreatic secretion, correspond with the three phases of gastric secretion., 1. CEPHALIC PHASE, As in case of gastric secretion, cephalic phase is regulat, ed by nervous mechanism through reflex action., Two types of reflexes occur:, 1. Unconditioned reflex, 2. Conditioned reflex., , Unconditioned Reflex, Unconditioned reflex is the inborn reflex. When food, is placed in the mouth, salivary secretion (Chapter, 37) and gastric secretion (Chapter 38) are induced., Simultaneously, pancreatic secretion also occurs., Stages of reflex action:, i. Presence of food in the mouth stimulates the, taste buds and other receptors in the mouth, ii. Sensory (afferent) impulses from mouth reach, dorsal nucleus of vagus and efferent impulses, reach pancreatic acini via vagal efferent nerve, fibers, iii. Vagal efferent nerve endings secrete acetyl, choline, which stimulates pancreatic secretion., Conditioned Reflex, Conditioned reflex is the reflex response acquired by, previous experience (Chapter 162). Presence of food in, the mouth is not necessary to elicit this reflex. The sight,, smell, hearing or thought of food, which induce salivary, secretion and gastric secretion induce pancreatic, secretion also., Stages of reflex action:, i. Impulses from the special sensory organs (eye,, ear and nose) pass through afferent fibers of
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246 Section 4 t Digestive System, neural circuits to the cerebral cortex. Thinking of, food stimulates the cerebral cortex directly, ii. From cerebral cortex, the impulses pass through, dorsal nucleus of vagus and vagal efferents and, reach pancreatic acini, iii. Vagal nerve endings secrete acetylcholine,, which stimulates pancreatic secretion., 2. GASTRIC PHASE, Secretion of pancreatic juice when food enters the, stomach is known as gastric phase. This phase of, pancreatic secretion is under hormonal control. The, hormone involved is gastrin., When food enters the stomach, gastrin is secreted, from stomach (Chapter 39). When gastrin is transported, to pancreas through blood, it stimulates the pancreatic, secretion. The pancreatic juice secreted during gastric, phase is rich in enzymes., 3. INTESTINAL PHASE, Intestinal phase is the secretion of pancreatic juice when, the chyme enters the intestine. This phase is also under, hormonal control., When chyme enters the intestine, many hormones, are released. Some hormones stimulate the pancreatic, secretion and some hormones inhibit the pancreatic, secretion., , Hormones Stimulating Pancreatic Secretion, i. Secretin, ii. Cholecystokinin., Secretin, Secretin is produced by S cells of mucous membrane, in duodenum and jejunum. It is secreted as inactive, prosecretin, which is activated into secretin by acid, chyme., The stimulant for the release and activation of, prosecretin is the acid chyme entering intestine., Products of protein digestion also stimulate the hormo, nal secretion., Action of secretin, Secretin stimulates the secretion of watery juice which is, rich in of bicarbonate ion and high in volume. It increases, the pancreactic secretion by acting on pancreatic, ductules via cyclic AMP (messenger). Other actions of, secretin are explained in Chapter 44., Cholecystokinin, Cholecystokinin (CCK) is also called cholecystokinin, pancreozymin (CCKPZ). It is secreted by I cells in, duodenal and jejunal mucosa. The stimulant for the, , FIGURE 39.2: Schematic diagram showing the regulation of pancreatic secretion
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Chapter 39 t Pancreas 247, release of this hormone is the chyme containing, digestive products such as fatty acids, peptides and, amino acids., Action of cholecystokinin, Cholecystokinin stimulates the secretion of pancreatic, juice which is rich in enzyme and low in volume,, by acting on pancreatic acinar cells via inosine, triphosphate (second messenger). The other actions of, cholecystokinin are described in Chapter 44., Hormones Inhibiting Pancreatic Secretion, i. Pancreatic polypeptide (PP) secreted by PP, cells in islets of Langerhans of pancreas, ii. Somatostatin secreted by D cells in islets of, Langerhans of pancreas, iii. Peptide YY secreted by intestinal mucosa, iv. Peptides like ghrelin and leptin, Refer Chapter 44 for details of these hormones., , COLLECTION OF PANCREATIC JUICE, IN ANIMALS, In animals, the pancreatic juice is collected by connecting, a fistula between the pancreatic duct and the opening in, the abdominal wall., IN HUMAN, In human beings, a multilumen tube is inserted through, nose or mouth, till the tip of this tube reaches the intestine, near the ampulla of Vater. The tube has a marking. The, entrance of the tip of the tube into the intestine near, the ampulla is indicated when this line comes near the, mouth. The tube has three lumens. Small balloons are, attached to the two outer lumens. When balloons are, inflated by air, the intestine near the ampulla is enlarged., Now, the pancreatic juice is collected through the middle, lumen by means of aspiration., , APPLIED PHYSIOLOGY, PANCREATITIS, Pancreatitis is the inflammation of pancreatic acini. It is, a rare but dangerous disease., Pancreatitis is of two types:, 1. Acute pancreatitis, 2. Chronic pancreatitis., , 1. Acute Pancreatitis, Acute pancreatitis is more severe and it occurs because, of heavy alcohol intake or gallstones., Features of acute pancreatitis:, i., ii., iii., iv., v., , Severe upper abdominal pain, Nausea and vomiting, Loss of appetite and weight, Fever, Shock., , 2. Chronic Pancreatitis, Chronic pancreatitis develops due to repeated acute, inflammation or chronic damage to pancreas., Causes of chronic pancreatitis, i. Longtime consumption of alcohol, ii. Chronic obstruction of ampulla of Vater by, gallstone, iii. Hereditary cause (passed on genetically from, one generation to another), iv. Congenital abnormalities of pancreatic duct, v. Cystic fibrosis, a generalized disorder affecting, the functions of many organs such as lungs, (due to excessive mucus), exocrine glands like, pancreas, biliary system and immune system, vi. Malnutrition (poor nutrition; mal = bad), vii. Idiopathic pancreatitis (due to unknown cause)., Features of chronic pancreatitis, i. Complete destruction of pancreas: During the, obstruction of biliary ducts, more amount of, trypsinogen and other enzymes are accumulated., In spite of the presence of trypsin inhibitor in, acini, some trypsinogen is activated. Trypsin, in turn activates other proteolytic enzymes. All, these enzymes destroy the pancreatic tissues, completely, ii. Absence of pancreatic enzymes: Pancreatitis, is more dangerous because the destruction of, acinar cells in pancreas leads to deficiency or, total absence of pancreatic enzymes. So the, digestive processes are affected; worst affected
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248 Section 4 t Digestive System, , iii., iv., v., vi., , is fat digestion that results in steatorrhea (see, below), Severe pain in upper abdominal region, which, radiates to the back, Fever, nausea and vomiting, Tender and swollen abdomen, Weight loss., , STEATORRHEA, Steatorrhea is the formation of bulky, foulsmelling,, frothy and claycolored stools with large quantity of, undigested fat because of impaired digestion and, absorption of fat., , Causes of Steatorrhea, Any condition that causes indigestion or malabsorption, of fat leads to steatorrhea. Various causes of steatorrhea, are:, 1. Lack of pancreatic lipase: Since most of the fat is, digested only by pancreatic lipase, its deficiency, leads to steatorrhea, 2. Liver disease affecting secretion of bile: Bile salts, are essential for the digestion of fat by lipase and, absorption of fat from intestine. Absence of bile, salts results in excretion of fatty stool, 3. Celiac disease: Atrophy of intestinal villi leads to, malabsorption, resulting in steatorrhea, 4. Cystic fibrosis (see above).
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Liver and Gallbladder, , , , , , , , , , , , , , Chapter, , 40, , FUNCTIONAL ANATOMY OF LIVER AND BILIARY SYSTEM, BLOOD SUPPLY TO LIVER, PROPERTIES AND COMPOSITION OF BILE, SECRETION OF BILE, STORAGE OF BILE, BILE SALTS, BILE PIGMENTS, FUNCTIONS OF BILE, FUNCTIONS OF LIVER, GALLBLADDER, REGULATION OF BILE SECRETION, APPLIED PHYSIOLOGY, , FUNCTIONAL ANATOMY OF LIVER, AND BILIARY SYSTEM, Liver is a dual organ having both secretory and excretory, functions. It is the largest gland in the body, weighing, about 1.5 kg in man. It is located in the upper and right, side of the abdominal cavity, immediately beneath, diaphragm., LIVER, , Hepatocytes and Hepatic Plates, Hepatocytes are arranged in columns, which form the, hepatic plates. Each plate is made up of two columns of, cells. In between the two columns of each plate lies a, bile canaliculus (Fig. 40.2)., In between the neighboring plates, a blood space, called sinusoid is present. Sinusoid is lined by the, endothelial cells. In between the endothelial cells some, special macrophages called Kupffer cells are present., , Hepatic Lobes, , Portal Triads, , Liver is made up of many lobes called hepatic lobes, (Fig. 40.1). Each lobe consists of many lobules called, hepatic lobules., , Each lobule is surrounded by many portal triads. Each, portal triad consists of three vessels:, 1. A branch of hepatic artery, 2. A branch of portal vein, 3. A tributary of bile duct., Branches of hepatic artery and portal vein open, into the sinusoid. Sinusoid opens into the central vein., Central vein empties into hepatic vein., Bile is secreted by hepatic cells and emptied into, bile canaliculus. From canaliculus, the bile enters the, , Hepatic Lobules, Hepatic lobule is the structural and functional unit of, liver. There are about 50,000 to 100,000 lobules in the, liver. The lobule is a honeycomb-like structure and it is, made up of liver cells called hepatocytes.
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250 Section 4 t Digestive System, hepatic artery divides into many branches. Each branch, enters a portal triad., , FIGURE 40.1: Posterior surface of liver, , tributary of bile duct. Tributaries of bile duct from, canaliculi of neighboring lobules unite to form small bile, ducts. These small bile ducts join together and finally, form left and right hepatic ducts, which emerge out of, liver., BILIARY SYSTEM, Biliary system or extrahepatic biliary apparatus is, formed by gallbladder and extrahepatic bile ducts (bile, ducts outside the liver). Right and left hepatic bile ducts, which come out of liver join to form common hepatic, duct. It unites with the cystic duct from gallbladder to, form common bile duct (Fig. 40.3). All these ducts have, similar structures., Common bile duct unites with pancreatic duct to, form the common hepatopancreatic duct or ampulla of, Vater, which opens into the duodenum., There is a sphincter called sphincter of Oddi at, the lower part of common bile duct, before it joins the, pancreatic duct. It is formed by smooth muscle fibers of, common bile duct. It is normally kept closed; so the bile, secreted from liver enters gallbladder where it is stored., Upon appropriate stimulation, the sphincter opens and, allows flow of bile from gallbladder into the intestine., , FIGURE 40.2: Hepatic lobule, , BLOOD SUPPLY TO LIVER, Liver receives maximum blood supply of about 1,500, mL/minute. It receives blood from two sources, namely, the hepatic artery and portal vein (Fig. 40.4)., HEPATIC ARTERY, Hepatic artery arises directly from aorta and supplies, oxygenated blood to liver. After entering the liver, the, , FIGURE 40.3: Biliary system
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Chapter 40 t Liver and Gallbladder 251, , FIGURE 40.5: Enterohepatic circulation, FIGURE 40.4: Schematic diagram of blood flow through liver, , PORTAL VEIN, Portal vein is formed by superior mesenteric vein and, splenic vein. It brings deoxygenated blood from stomach,, intestine, spleen and pancreas. Portal blood is rich in, monosaccharides and amino acids. It also contains bile, salts, bilirubin, urobilinogen and GI hormones. However,, the oxygen content is less in portal blood., Flow of blood from intestine to liver through portal, vein is known as enterohepatic circulation (Fig. 40.5)., The blood from hepatic artery mixes with blood from, portal vein in hepatic sinusoids. Hepatic cells obtain, oxygen and nutrients from the sinusoid., HEPATIC VEIN, Substances synthesized by hepatic cells, waste products, and carbon dioxide are discharged into sinusoids., Sinusoids drain them into central vein of the lobule., Central veins from many lobules unite to form bigger, veins, which ultimately form hepatic veins (right and left), which open into inferior vena cava., , PROPERTIES AND COMPOSITION, OF BILE, PROPERTIES OF BILE, Volume, Reaction, , : 800 to 1,200 mL/day, : Alkaline, , pH, : 8 to 8.6, Specific gravity : 1.010 to 1.011, Color, : Golden yellow or green., COMPOSITION OF BILE, Bile contains 97.6% of water and 2.4% of solids. Solids, include organic and inorganic substances. Refer Fig., 40.6 for details., , SECRETION OF BILE, Bile is secreted by hepatocytes. The initial bile secreted, by hepatocytes contains large quantity of bile acids,, bile pigments, cholesterol, lecithin and fatty acids., From hepatocytes, bile is released into canaliculi. From, here, it passes through small ducts and hepatic ducts, and reaches the common hepatic duct. From common, hepatic duct, bile is diverted either directly into the, intestine or into the gallbladder., Sodium, bicarbonate and water are added to bile, when it passes through the ducts. These substances, are secreted by the epithelial cells of the ducts. Addition, of sodium, bicarbonate and water increases the total, quantity of bile., , STORAGE OF BILE, Most of the bile from liver enters the gallbladder, where it, is stored. It is released from gallbladder into the intestine, whenever it is required. When bile is stored in gallbladder,
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252 Section 4 t Digestive System, TABLE 40.1: Differences between liver bile, and gallbladder bile, Types of entities, , Liver bile, , pH, , 8 to 8.6, , Gallbladder bile, 7 to 7.6, , Specific gravity, , 1010 to 1011, , 1026 to 1032, , Water content, , 97.6%, , 89%, , Solids, , 2.4%, , 11%, , Bile Salts, , 0.5 g/dL, , 6.0 g/dL, , Bile Pigments, , 0.05 g/dL, , 0.3 g/dL, , Cholesterol, , 0.1 g/dL, , 0.5 g/dL, , Fatty Acids, , 0.2 g/dL, , 1.2 g/dL, , Lecithin, , 0.05 g/dL, , 0.4 g/dL, , Mucin, , Absent, , Present, , Organic substances, , FIGURE 40.6: Composition of bile, , it undergoes many changes both in quality and quantity, such as:, 1. Volume is decreased because of absorption of, a large amount of water and electrolytes (except, calcium and potassium), 2. Concentration of bile salts, bile pigments, cholesterol,, fatty acids and lecithin is increased because of, absorption of water and electrolytes, 3. The pH is decreased slightly, 4. Specific gravity is increased, 5. Mucin is added to bile (Table 40.1)., , BILE SALTS, Bile salts are the sodium and potassium salts of bile, acids, which are conjugated with glycine or taurine., FORMATION OF BILE SALTS, Bile salts are formed from bile acids. There are two, primary bile acids in human, namely cholic acid and, chenodeoxycholic acid, which are formed in liver and, enter the intestine through bile. Due to the bacterial action, in the intestine, the primary bile acids are converted into, secondary bile acids:, , Cholic acid → deoxycholic acid, Chenodeoxycholic acid → lithocholic acid, Secondary bile acids from intestine are transported, back to liver through enterohepatic circulation. In liver,, the secondary bile acids are conjugated with glycine, (amino acid) or taurin (derivative of an amino acid) and, form conjugated bile acids, namely glycocholic acid, and taurocholic acids. These bile acids combine with, sodium or potassium ions to form the salts, sodium, or potassium glycocholate and sodium or potassium, taurocholate (Fig. 40.7)., , Inorganic substances, Sodium, , 150 mEq/L, , 135 mEq/L, , Calcium, , 4 mEq/L, , 22 mEq/L, , Potassium, , 5 mEq/L, , 12 mEq/L, , 100 mEq/L, , 10 mEq/L, , 30 mEq/L, , 10 mEq/L, , Chloride, Bicarbonate, , ENTEROHEPATIC CIRCULATION, OF BILE SALTS, Enterohepatic circulation is the transport of substances, from small intestine to liver through portal vein. About, 90% to 95% of bile salts from intestine are transported to, liver through enterohepatic circulation. Remaining 5% to, 10% of the bile salts enter large intestine. Here, the bile, salts are converted into deoxycholate and lithocholate,, which are excreted in feces., FUNCTIONS OF BILE SALTS, Bile salts are required for digestion and absorption of, fats in the intestine. The functions of bile salts are:, 1. Emulsification of Fats, Emulsification is the process by which the fat globules, are broken down into minute droplets and made in the, form of a milky fluid called emulsion in small intestine,, by the action of bile salts., Lipolytic enzymes of GI tract cannot digest the fats, directly because the fats are insoluble in water due to the, surface tension. Bile salts emulsify the fats by reducing, the surface tension due to their detergent action. Now, the fats can be easily digested by lipolytic enzymes.
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Chapter 40 t Liver and Gallbladder 253, , FIGURE 40.7: Formation of bile salts, , Unemulsified fat usually passes through the intes, tine and then it is eliminated in feces., Emulsification of fats by bile salts needs the pres, ence of lecithin from bile., , salts act as cholagogues indirectly by stimulating the, secretion of hormone cholecystokinin. This hormone cau, ses contraction of gallbladder, resulting in release of bile., , 2. Absorption of Fats, , Laxative is an agent which induces defecation. Bile salts, act as laxatives by stimulating peristaltic movements of, the intestine., , Bile salts help in the absorption of digested fats from, intestine into blood. Bile salts combine with fats and, make complexes of fats called micelles. The fats in the, form of micelles can be absorbed easily., 3. Choleretic Action, Bile salts stimulate the secretion of bile from liver. This, action is called choleretic action., 4. Cholagogue Action, Cholagogue is an agent which causes contraction of, gallbladder and release of bile into the intestine. Bile, , 5. Laxative Action, , 6. Prevention of Gallstone Formation, Bile salts prevent the formation of gallstone by keeping, the cholesterol and lecithin in solution. In the absence, of bile salts, cholesterol precipitates along with lecithin, and forms gallstone., , BILE PIGMENTS, Bile pigments are the excretory products in bile. Bilirubin, and biliverdin are the two bile pigments and bilirubin is, the major bile pigment in human beings.
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254 Section 4 t Digestive System, Bile pigments are formed during the breakdown of, hemoglobin, which is released from the destroyed RBCs, in the reticuloendothelial system (Fig. 40.8)., FORMATION AND EXCRETION, OF BILE PIGMENTS, Stages of formation and circulation of bile pigments:, 1. Senile erythrocytes are destroyed in reticuloen, dothelial system and hemoglobin is released from, them, 2. Hemoglobin is broken into globin and heme, 3. Heme is split into iron and the pigment biliverdin, 4. Iron goes to iron pool and is reused, 5. First formed pigment biliverdin is reduced to bilirubin., 6. Bilirubin is released into blood from the reticulo, endothelial cells, 7. In blood, the bilirubin is transported by the plasma, protein, albumin. Bilirubin circulating in the blood is, called free bilirubin or unconjugated bilirubin, 8. Within few hours after entering the circulation, the, free bilirubin is taken up by the liver cells, 9. In the liver, it is conjugated with glucuronic acid to, form conjugated bilirubin, 10. Conjugated bilirubin is then excreted into intestine, through bile., , FATE OF CONJUGATED BILIRUBIN, Stages of excretion of conjugated bilirubin:, 1. In intestine, 50% of the conjugated bilirubin is, converted into urobilinogen by intestinal bacteria., First the conjugated bilirubin is deconjugated into free, bilirubin, which is later reduced into urobilinogen., 2. Remaining 50% of conjugated bilirubin from intestine, is absorbed into blood and enters the liver through, portal vein (enterohepatic circulation). From liver, it, is reexcreted in bile, 3. Most of the urobilinogen from intestine enters liver, via enterohepatic circulation. Later, it is reexcreted, through bile, 4. About 5% of urobilinogen is excreted by kidney, through urine. In urine, due to exposure to air, the, urobilinogen is converted into urobilin by oxidation, 5. Some of the urobilinogen is excreted in feces as, stercobilinogen. In feces, stercobilinogen is oxidized, to stercobilin., NORMAL PLASMA LEVELS OF BILIRUBIN, Normal bilirubin (Total bilirubin) content in plasma is 0.5, to 1.5 mg/dL. When it exceeds 1mg/dL, the condition is, called hyperbilirubinemia. When it exceeds 2 mg/dL,, jaundice occurs., , FIGURE 40.8: Formation and circulation of bile pigments
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Chapter 40 t Liver and Gallbladder 255, , FUNCTIONS OF BILE, , FUNCTIONS OF LIVER, , Most of the functions of bile are due to the bile salts., , Liver is the largest gland and one of the vital organs of the, body. It performs many vital metabolic and homeostatic, functions, which are summarized below., , 1. DIGESTIVE FUNCTION, Refer functions of bile salts., 2. ABSORPTIVE FUNCTIONS, Refer functions of bile salts., 3. EXCRETORY FUNCTIONS, Bile pigments are the major excretory products of the, bile. Other substances excreted in bile are:, i. Heavy metals like copper and iron, ii. Some bacteria like typhoid bacteria, iii. Some toxins, iv. Cholesterol, v. Lecithin, vi. Alkaline phosphatase., 4. LAXATIVE ACTION, Bile salts act as laxatives (see above)., 5. ANTISEPTIC ACTION, Bile inhibits the growth of certain bacteria in the lumen, of intestine by its natural detergent action., 6. CHOLERETIC ACTION, Bile salts have the choleretic action (see above)., 7. MAINTENANCE OF pH IN, GASTROINTESTINAL TRACT, , 1. METABOLIC FUNCTION, Liver is the organ where maximum metabolic reactions, such as metabolism of carbohydrates, proteins, fats,, vitamins and many hormones are carried out., 2. STORAGE FUNCTION, Many substances like glycogen, amino acids, iron, folic, acid and vitamins A, B12 and D are stored in liver., 3. SYNTHETIC FUNCTION, Liver produces glucose by gluconeogenesis. It synthe, sizes all the plasma proteins and other proteins (except, immunoglobulins) such as clotting factors, complement, factors and hormonebinding proteins. It also synthesizes, steroids, somatomedin and heparin., 4. SECRETION OF BILE, Liver secretes bile which contains bile salts, bile, pigments, cholesterol, fatty acids and lecithin., The functions of bile are mainly due to bile salts. Bile, salts are required for digestion and absorption of fats in, the intestine. Bile helps to carry away waste products, and breakdown fats, which are excreted through feces, or urine., 5. EXCRETORY FUNCTION, , As bile is highly alkaline, it neutralizes the acid chyme, which enters the intestine from stomach. Thus, an, optimum pH is maintained for the action of digestive, enzymes., , Liver excretes cholesterol, bile pigments, heavy metals, (like lead, arsenic and bismuth), toxins, bacteria and, virus (like that of yellow fever) through bile., , 8. PREVENTION OF GALLSTONE FORMATION, , 6. HEAT PRODUCTION, , Refer function of bile salts., 9. LUBRICATION FUNCTION, , Enormous amount of heat is produced in the liver, because of metabolic reactions. Liver is the organ where, maximum heat is produced., , The mucin in bile acts as a lubricant for the chyme in, intestine., , 7. HEMOPOIETIC FUNCTION, , 10. CHOLAGOGUE ACTION, Bile salts act as cholagogues (see above)., , In fetus (hepatic stage), liver produces the blood, cells (Chapter 10). It stores vitamin B12 necessary, for erythropoiesis and iron necessary for synthesis
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256 Section 4 t Digestive System, of hemoglobin. Liver produces thrombopoietin that, promotes production of thrombocytes., 8. HEMOLYTIC FUNCTION, The senile RBCs after a lifespan of 120 days are, destroyed by reticuloendothelial cells (Kupffer cells) of, liver., 9. INACTIVATION OF HORMONES, AND DRUGS, Liver catabolizes the hormones such as growth hormone,, parathormone, cortisol, insulin, glucagon and estrogen., It also inactivates the drugs, particularly the fatsoluble, drugs. The fatsoluble drugs are converted into water, soluble substances, which are excreted through bile or, urine., 10. DEFENSIVE AND DETOXIFICATION, FUNCTIONS, Reticuloendothelial cells (Kupffer cells) of the liver play, an important role in the defense of the body. Liver is also, involved in the detoxification of the foreign bodies., i. Foreign bodies such as bacteria or antigens are, swallowed and digested by reticuloendothelial, cells of liver by means of phagocytosis., ii. Reticuloendothelial cells of liver also produce, substances like interleukins and tumor necrosis, factors, which activate the immune system of, the body (Chapter 17)., iii. Liver cells are involved in the removal of toxic, property of various harmful substances. Removal, of toxic property of the harmful agent is known, as detoxification., Detoxification in liver occurs in two ways:, a. Total destruction of the substances by means, of metabolic degradation., b. Conversion of toxic substances into non, toxic materials by means of conjugation with, glucuronic acid or sulfates., , GALLBLADDER, Bile secreted from liver is stored in gallbladder. The, capacity of gallbladder is approximately 50 mL., Gallbladder is not essential for life and it is removed, (cholecystectomy) in patients suffering from gallbladder, dysfunction. After cholecystectomy, patients do not, suffer from any major disadvantage. In some species,, gallbladder is absent., , FUNCTIONS OF GALLBLADDER, Major functions of gallbladder are the storage and, concentration of bile., 1. Storage of Bile, Bile is continuously secreted from liver. But it is released, into intestine only intermittently and most of the bile is, stored in gallbladder till it is required., 2. Concentration of Bile, Bile is concentrated while it is stored in gallbladder., The mucosa of gallbladder rapidly reabsorbs water and, electrolytes, except calcium and potassium. But the, bile salts, bile pigments, cholesterol and lecithin are not, reabsorbed. So, the concentration of these substances, in bile increases 5 to 10 times (Fig. 40.9)., 3. Alteration of pH of Bile, The pH of bile decreases from 8 – 8.6 to 7 – 7.6 and it, becomes less alkaline when it is stored in gallbladder., 4. Secretion of Mucin, Gallbladder secretes mucin and adds it to bile. When bile, is released into the intestine, mucin acts as a lubricant, for movement of chyme in the intestine., 5. Maintenance of Pressure in Biliary System, Due to the concentrating capacity, gallbladder maintains, a pressure of about 7 cm H2O in biliary system. This, pressure in the biliary system is essential for the release, of bile into the intestine., FILLING AND EMPTYING OF GALLBLADDER, Usually, the sphincter of Oddi is closed during fasting, and the pressure in the biliary system is only 7 cm H2O., Because of this pressure, the bile from liver enters the, gallbladder., While taking food or when chyme enters the, intestine, gallbladder contracts along with relaxation of, sphincter of Oddi. Now, the pressure increases to about, 20 cm H2O. Because of the increase in pressure, the, bile from gallbladder enters the intestine. Contraction, of gallbladder is influenced by neural and hormonal, factors.
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Chapter 40 t Liver and Gallbladder 257, , FIGURE 40.9: Diagram showing the formation of bile from liver and changes taking place in the composition of gallbladder bile, , 1. Neural Factor, Stimulation of parasympathetic nerve (vagus) causes, contraction of gallbladder by releasing acetylcholine., The vagal stimulation occurs during the cephalic phase, and gastric phase of gastric secretion., 2. Hormonal Factor, When a fatty chyme enters the intestine from stomach,, the intestine secretes the cholecystokinin, which causes, contraction of the gallbladder., , REGULATION OF BILE SECRETION, Bile secretion is a continuous process though the amount, is less during fasting. It starts increasing after meals and, continues for three hours. Secretion of bile from liver, and release of bile from the gallbladder are influenced, by some chemical factors, which are categorized into, three groups:, , 1. Choleretics, 2. Cholagogue, 3. Hydrocholeretic agents., 1. Choleretics, Substances which increase the secretion of bile from, liver are known as choleretics., Effective choleretic agents are:, i. Acetylcholine, ii. Secretin, iii. Cholecystokinin, iv. Acid chyme in intestine, v. Bile salts., 2. Cholagogues, Cholagogue is an agent which increases the release of, bile into the intestine by contracting gallbladder.
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258 Section 4 t Digestive System, Common cholagogues are:, i. Bile salts, ii. Calcium, iii. Fatty acids, iv. Amino acids, v. Inorganic acids, All these substances stimulate the secretion of, cholecystokinin, which in turn causes contraction of, gallbladder and flow of bile into intestine., , Common causes of hemolytic jaundice are:, i. Renal disorder, ii. Hypersplenism, iii. Burns, iv. Infections such as malaria, v. Hemoglobin abnormalities such as sickle cell, anemia or thalassemia, vi. Drugs or chemical substances causing red cell, damage, vii. Autoimmune diseases., , 3. Hydrocholeretic Agents, Hydrocholeretic agent is a substance which causes, the secretion of bile from liver, with large amount of, water and less amount of solids. Hydrochloric acid is a, hydrocholeretic agent., , 2. Hepatic or Hepatocellular or, Cholestatic Jaundice, , APPLIED PHYSIOLOGY, , Hepatic jaundice is the type of jaundice that occurs due, to the damage of hepatic cells. Because of the damage,, the conjugated bilirubin from liver cannot be excreted, and it returns to blood., , JAUNDICE OR ICTERUS, , Causes, , Jaundice or icterus is the condition characterized by, yellow coloration of the skin, mucous membrane and, deeper tissues due to increased bilirubin level in blood., The word jaundice is derived from the French word, ‘jaune’ meaning yellow., The normal serum bilirubin level is 0.5 to 1.5 mg/dL., Jaundice occurs when bilirubin level exceeds 2 mg/dL., Types of Jaundice, Jaundice is classified into three types:, 1. Prehepatic or hemolytic jaundice, 2. Hepatic or hepatocellular jaundice, 3. Posthepatic or obstructive jaundice., 1. Prehepatic or Hemolytic Jaundice, Hemolytic jaundice is the type of jaundice that occurs, because of excessive destruction of RBCs resulting in, increased blood level of free (unconjugated) bilirubin. In, this condition, the excretory function of liver is normal., But the quantity of bilirubin increases enormously. The, liver cells cannot excrete that much excess bilirubin, rapidly. Unconjugated bilirubin is insoluble in water and, is not excreted in urine. So, it accumulates in the blood, resulting in jaundice., Formation of urobilinogen also increases resulting in, the excretion of more amount of urobilinogen in urine., Causes, Any condition that causes hemolytic anemia can lead to, hemolytic jaundice., , i. Infection (infective jaundice) by virus, resulting, in hepatitis (viral hepatitis), ii. Alcoholic hepatitis, iii. Cirrhosis of liver, iv. Exposure to toxic materials., 3. Posthepatic or Obstructive or, Extrahepatic Jaundice, Posthepatic type of jaundice occurs because of the, obstruction of bile flow at any level of the biliary system., The bile cannot be excreted into small intestine. So, bile, salts and bile pigments enter the circulation. The blood, contains more amount of conjugated bilirubin (Table, 40.2)., Causes, i. Gallstones, ii. Cancer of biliary system or pancreas., HEPATITIS, Hepatitis is the liver damage caused by many agents. It, is characterized by swelling and inadequate functioning, of liver. Hepatitis may be acute or chronic. In severe, conditions, it may lead to liver failure and death., Causes and Types, 1. Viral infection (viral hepatitis: see below), 2. Bacterial infection like leptospirosis and Q fever, 3. Excess consumption of alcohol
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Chapter 40 t Liver and Gallbladder 259, TABLE 40.2: Features of different types of jaundice, Features, , Prehepatic jaundice, (Hemolytic), , Hepatic jaundice, (hepatocellular), , Posthepatic jaundice, (Obstructive), , Cause, , Excess breakdown of RBCs, , Liver damage, , Obstruction of bile ducts, , Type of bilirubin in blood, , Unconjucated, , Conjugated and unconjugated, , Conjugated, , Urinary excretion of, urobilinogen, , Increases, , Decreases, , Decreases, Absent in severe obstruction, , Fecal excretion of, stercobilinogen, , Increases, , Decreases (pale feces), , Absent (claycolored feces), , van den Bergh reaction, , Indirect – positive, , Biphasic, , Direct – positive, , Liver functions, , Normal, , Abnormal, , Exaggerated, , Blood picture, , Anemia, Reticulocytosis, Abnormal RBC, , Normal, , Normal, , Plasma albumin and, globulin, , Normal, , Albumin – increases, Globulin – increases, A : G ratio – decreases, , Normal, , Hemorrhagic tendency, , Absent, , Present due to lack of vitamin K, , Present due to lack of vitamin K, , 4., 5., 6., 7., 8., , Excess administration of drugs like paracetamol, Poisons like carbon tetrachloride and aflatoxin, Wilson disease (Chapter 151), Circulatory insufficiency, Inheritance from mother during parturition., , Viral Hepatitis, Viral hepatitis is the type of hepatitis caused by viruses., It is caused by two types of viruses, hepatitis A and, hepatitis B., Causes of viral hepatitis, i. Mainly by intake of water and food contaminated, with hepatitis virus, ii. Sharing needles with infected persons, iii. Accidental prick by infected needle, iv. Having unprotected sex with infected persons, v. Inheritance from mother during parturition, vi. Blood transfusion from infected donors., Hepatitis caused by hepatitis B virus is more, common and considered more serious because it may, lead to cirrhosis and cancer of liver., Features of Hepatitis, 1., 2., 3., 4., 5., , Fever, Nausea, Vomiting, diarrhea and loss of appetite, Headache and weakness, In addition, chronic hepatitis is characterized by, , i., ii., iii., iv., v., , Stomach pain, Paleness of skin, Darkcolored urine and pale stool, Jaundice, Personality changes., , CIRRHOSIS OF LIVER, Cirrhosis of liver refers to inflammation and damage of, parenchyma of liver. It results in degeneration of hepatic, cells and dysfunction of liver., Causes, 1. Infection, 2. Retention of bile in liver due to obstruction of ducts, of biliary system, 3. Enlargement of liver due to intoxication, 4. Inflammation around liver (perihepatitis), 5. Infiltration of fat in hepatic cells., Features, 1., 2., 3., 4., 5., 6., 7., 8., , Fever, nausea and vomiting, Jaundice, Increased heart rate and cardiac output, Portal hypertension, Muscular weakness and wasting of muscles, Drowsiness, Lack of concentration and confused state of mind, Coma in advanced stages.
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260 Section 4 t Digestive System, GALLSTONES, Definitions, Gallstone is a solid crystal deposit that is formed by, cholesterol, calcium ions and bile pigments in the gall, bladder or bile duct. Cholelithiasis is the presence of, gallstones in gallbladder. Choledocholithiasis is the, presence of gallstones in the bile ducts., Formation of Gallstones, Normally, cholesterol present in the bile combines, with bile salts and lecithin, which make the cholesterol, soluble in water. Under some abnormal conditions, this, watersoluble cholesterol precipitates resulting in the, formation of gallstone., Initially, small quantity of cholesterol begins to, precipitate forming many small crystals of cholesterol, in the mucosa of gallbladder. This stimulates further, formation of crystals and the crystals grow larger and, larger. Later, bile pigments and calcium are attached to, these crystals, resulting in formation of gallstones., Causes for Gallstone Formation, 1., 2., 3., 4., , Reduction in bile salts and/or lecithin, Excess of cholesterol, Disturbed cholesterol metabolism, Excess of calcium ions due to increased concen, tration of bile, , 5. Damage or infection of gallbladder epithelium. It, alters the absorptive function of the mucous mem, brane of the gallbladder. Sometimes, there is, excessive absorption of water or even bile salts,, leading to increased concentration of cholesterol,, bile pigments and calcium ions, 6. Obstruction of bile flow from the gallbladder., Diagnosis of Gallstone, Presence of gallstone is diagnosed by ultrasound, scanning and cholangiography. Cholangiography is the, radiological study of biliary ducts after the administration, of a contrast medium., Features, Common feature of gallstone is the pain in stomach area, or in upper right part of the belly under the ribs. Other, features include nausea, vomiting, abdominal bloating, and indigestion., Treatment for Gallstone, Simple cholesterol gallstones can be dissolved over, a period of one or two years by giving 1 to 1.5 gm, of chemodeoxycholic acid daily. This increases the, concentration of bile acids. So, excessive concentration, of bile does not occur., In severe conditions, the gallbladder has to be, removed (cholecystectomy). Laparoscopic surgery is, the common method.
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Chapter, , Small Intestine, , , , , , , , , , 41, , FUNCTIONAL ANATOMY, INTESTINAL VILLI AND GLANDS, PROPERTIES AND COMPOSITION OF SUCCUS ENTERICUS, FUNCTIONS OF SUCCUS ENTERICUS, FUNCTIONS OF SMALL INTESTINE, REGULATION OF SECRETION OF SUCCUS ENTERICUS, METHODS OF COLLECTION OF SUCCUS ENTERICUS, APPLIED PHYSIOLOGY, , FUNCTIONAL ANATOMY, Small intestine is the part of gastrointestinal (GI) tract,, extending between the pyloric sphincter of stomach, and ileocecal valve, which opens into large intestine. It, is called small intestine because of its small diameter,, compared to that of the large intestine. But it is longer, than large intestine. Its length is about 6 meter., Important function of small intestine is absorption., Maximum absorption of digested food products takes, place in small intestine., Small intestine consists of three portions:, 1. Proximal part known as duodenum, 2. Middle part known as jejunum, 3. Distal part known as ileum., Wall of the small intestine has all the four layers as, in stomach (Chapter 36)., , INTESTINAL VILLI AND GLANDS, OF SMALL INTESTINE, INTESTINAL VILLI, Mucous membrane of small intestine is covered by, minute projections called villi. The height of villi is about, 1 mm and the diameter is less than 1 mm., Villi are lined by columnar cells, which are called, enterocytes. Each enterocyte gives rise to hair-like, projections called microvilli. Villi and microvilli increase, , the surface area of mucous membrane by many folds., Within each villus, there is a central channel called, lacteal, which opens into lymphatic vessels. It contains, blood vessels also., CRYPTS OF LIEBERKÜHN OR, INTESTINAL GLANDS, Crypts of Lieberkühn or intestinal glands are simple, tubular glands of intestine. Intestinal glands do not, penetrate the muscularis mucosa of the intestinal wall,, but open into the lumen of intestine between the villi., Intestinal glands are lined by columnar cells. Lining of, each gland is continuous with epithelial lining of the villi, (Fig. 41.1)., Epithelial cells lining the intestinal glands undergo, division by mitosis at a faster rate. Newly formed cells, push the older cells upward over the lining of villi., These cells which move to villi are called enterocytes., Enterocytes secrete the enzymes. Old enterocytes are, continuously shed into lumen along with enzymes., Types of cells interposed between columnar cells of, intestinal glands:, 1. Argentaffin cells or enterochromaffin cells, which, secrete intrinsic factor of Castle, 2. Goblet cells, which secrete mucus, 3. Paneth cells, which secrete the cytokines called, defensins.
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262 Section 4 t Digestive System, , FUNCTIONS OF SUCCUS ENTERICUS, 1. DIGESTIVE FUNCTION, Enzymes of succus entericus act on the partially, digested food and convert them into final digestive, products. Enzymes are produced and released into, succus entericus by enterocytes of the villi., Proteolytic Enzymes, Proteolytic enzymes present in succus entericus are, the peptidases, which are given in Fig. 41.2. These, peptidases convert peptides into amino acids., Amylolytic Enzymes, , FIGURE 41.1: Intestinal gland and villus, , Amylolytic enzymes of succus entericus are listed in, Fig. 41.2., Lactase, sucrase and maltase convert the, disaccharides (lactose, sucrose and maltose) into two, molecules of monosaccharides (Table 41.1)., Dextrinase converts dextrin, maltose and maltriose, into glucose. Trehalase or trehalose glucohydrolase, causes hydrolysis of trehalose (carbohydrate present in, mushrooms and yeast) and converts it into glucose., , BRUNNER GLANDS, , Lipolytic Enzyme, , In addition to intestinal glands, the first part of duodenum, contains some mucus glands, which are called Brunner, glands. These glands penetrate muscularis mucosa and, extend up to the submucus coat of the intestinal wall., Brunner glands open into the lumen of intestine directly., Brunner gland secretes mucus and traces of enzymes., , Intestinal lipase acts on triglycerides and converts them, into fatty acids., , PROPERTIES AND COMPOSITION, OF SUCCUS ENTERICUS, Secretion from small intestine is called succus, entericus., PROPERTIES OF SUCCUS ENTERICUS, Volume : 1800 mL/day, Reaction : Alkaline, pH, : 8.3, COMPOSITION OF SUCCUS ENTERICUS, Succus entericus contains water (99.5%) and solids, (0.5%). Solids include organic and inorganic substances, (Fig. 41.2). Bicarbonate concentration is slightly high in, succus entericus., , 2. PROTECTIVE FUNCTION, i. Mucus present in the succus entericus protects, the intestinal wall from the acid chyme, which, enters the intestine from stomach; thereby it, prevents the intestinal ulcer., ii. Defensins secreted by paneth cells of intestinal, glands are the antimicrobial peptides., These peptides are called natural peptide antibiotics, because of their role in killing the phagocytosed, bacteria., 3. ACTIVATOR FUNCTION, Enterokinase present in intestinal juice activates, trypsinogen into trypsin. Trypsin, in turn activates other, enzymes (Chapter 39)., 4. HEMOPOIETIC FUNCTION, Intrinsic factor of Castle present in the intestine plays, an important role in erythropoiesis (Chapter 10). It is, necessary for the absorption of vitamin B12.
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Chapter 41 t Small Intestine 263, , FIGURE 41.2: Composition of succus entericus, , 5. HYDROLYTIC PROCESS, , 5. ACTIVATOR FUNCTION, , Intestinal juice helps in all the enzymatic reactions of, digestion., , Refer functions of succus entericus., 6. HEMOPOIETIC FUNCTION, , FUNCTIONS OF SMALL INTESTINE, 1. MECHANICAL FUNCTION, Mixing movements of small intestine help in the thorough, mixing of chyme with the digestive juices like succus, entericus, pancreatic juice and bile., , Refer functions of succus entericus., 7. HYDROLYTIC FUNCTION, Refer functions of succus entericus., TABLE 41.1: Digestive enzymes of succus entericus, , 2. SECRETORY FUNCTION, Small intestine secretes succus entericus, enterokinase, and the GI hormones., 3. HORMONAL FUNCTION, , Enzyme, , Substrate, , End products, , Peptidases, , Peptides, , Amino acids, , Sucrase, , Sucrose, , Fructose and glucose, , Maltase, , Maltose and, maltriose, , Glucose, , Small intestine secretes many GI hormones such as, secretin, cholecystokinin, etc. These hormones regulate, the movement of GI tract and secretory activities of small, intestine and pancreas (Chapter 44)., , Lactase, , Lactose, , Galactose and, glucose, , Dextrinase, , Dextrin, maltose, and maltriose, , Glucose, , 4. DIGESTIVE FUNCTION, , Trehalase, , Trehalose, , Glucose, , Refer functions of succus entericus., , Intestinal lipase, , Triglycerides, , Fatty acids
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264 Section 4 t Digestive System, 8. ABSORPTIVE FUNCTIONS, Presence of villi and microvilli in small intestinal mucosa, increases the surface area of mucosa. This facilitates, the absorptive function of intestine., Digested products of foodstuffs, proteins, carbohydrates, fats and other nutritive substances such as, vitamins, minerals and water are absorbed mostly in small, intestine. From the lumen of intestine, these substances, pass through lacteal of villi, cross the mucosa and enter, the blood directly or through lymphatics., Absorption of Carbohydrates, Refer Chapter 45., Absorption of Proteins, Refer Chapter 46., Absorption of Fats, , entericus. Stimulation of sympathetic nerves causes, vasoconstriction and decreases the secretion of succus, entericus. But, the role of these nerves in the regulation, of intestinal secretion in physiological conditions is, uncertain., However, the local nervous reflexes play an, important role in increasing the secretion of intestinal, juice. When chyme enters the small intestine, the mucosa, is stimulated by tactile stimuli or irritation. It causes the, development of local nervous reflexes, which stimulate, the glands of intestine., HORMONAL REGULATION, When chyme enters the small intestine, intestinal mucosa, secretes enterocrinin, secretin and cholecystokinin,, which promote the secretion of succus entericus by, stimulating the intestinal glands., , Refer Chapter 47., , METHODS OF COLLECTION, OF SUCCUS ENTERICUS, , Absorption of Water and Minerals, , IN HUMAN, , i. In small intestine, sodium is absorbed actively. It, is responsible for absorption of glucose, amino, acids and other substances by means of sodium, cotransport., ii. Water moves in or out of the intestinal lumen, until the osmotic pressure of intestinal contents, becomes equal to that of plasma., iii. In ileum, chloride ion is actively absorbed in, exchange for bicarbonate. The significance of, this exchange is not known., iv. Calcium is actively absorbed mostly in upper, part of small intestine., , In human beings, the intestinal juice is collected by, using multilumen tube. The multilumen tube is inserted, through nose or mouth, until the tip of this tube reaches, the intestine. A line is marked on the tube. Entrance of, tip of the tube into small intestine is indicated when this, line comes near the mouth. This tube has three lumens., To the outer two lumens, small balloons are attached., When these balloons are inflated, the intestine is, enlarged. Now, the intestinal juice is collected through, the middle lumen, by means of aspiration., IN ANIMALS, , Absorption of Vitamins, , Thiry Loop, , Most of the vitamins are absorbed in upper part of, small intestine and vitamin B12 is absorbed in ileum., Absorption of water-soluble vitamins is faster than fatsoluble vitamins., , A portion of intestine is separated from the gut by, incising at both ends. The cut ends of the main gut are, connected and the continuity is re-established. One, end of isolated segment is closed and the other end is, brought out through abdominal wall. It is called Thiry, loop or Thiry fistula., , REGULATION OF SECRETION, OF SUCCUS ENTERICUS, Secretion of succus entericus is regulated by both, nervous and hormonal mechanisms., NERVOUS REGULATION, Stimulation of parasympathetic nerves causes vasodilatation and increases the secretion of succus, , Thiry-Vella Loop, Thiry-Vella loop is the modified Thiry loop. In this, a, long segment of intestine is cut and separated from the, main gut. Both the ends of this segment are brought out, through the abdominal wall. The cut ends of the main, gut are joined.
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Chapter 41 t Small Intestine 265, , APPLIED PHYSIOLOGY, , Cause, , 1. MALABSORPTION, , The cause of this disease is not known and it may be, related to infectious organisms., , Malabsorption is the failure to absorb nutrients such as, proteins, carbohydrates, fats and vitamins., Malabsorption affects growth and development of, the body. It also causes specific diseases (see below)., 2. MALABSORPTION SYNDROME, Malabsorption syndrome is the condition characterized, by the failure of digestion and absorption in small, intestine. Malabsorption syndrome is generally caused, by Crohn’s disease, tropical sprue, steatorrhea and, celiac disease., , 3. CROHN’S DISEASE OR ENTERITIS, Enteritis is an inflammatory bowel disease (IBD), characterized by inflammation of small intestine. Usually, it, affects the lower part of small intestine, the ileum. The, inflammation causes malabsorption and diarrhea., Causes, Crohn’s disease develops because of abnormalities of, the immune system. The immune system reacts to a virus, or a bacterium, resulting in inflammation of the intestine., Features, i., ii., iii., iv., v., vi., , Malabsorption of vitamin, Weight loss, Abdominal pain, Diarrhea, Rectal bleeding, anemia and fever, Delayed or stunted growth in children., , 4. TROPICAL SPRUE, Tropical sprue is a malabsorption syndrome, affecting, the residents of or the visitors to tropical areas where, the disease is epidemic., , Features, i., ii., iii., iv., , Indigestion, Diarrhea, Anorexia and weight loss, Abdominal and muscle cramps., , 5. STEATORRHEA, Steatorrhea is the condition caused by deficiency of, pancreatic lipase, resulting in malabsorption of fat. Refer, Chapter 39 for details., 6. CELIAC DISEASE, Celiac disease is an autoimmune disorder characterized, by the damage of mucosa and atrophy of villi in small, intestine, resulting in impaired digestion and absorption., It is also known as gluten-sensitive enteropathy, celiac, sprue and non-tropical sprue., Cause, Celiac disease is caused by gluten. It is a protein present, in wheat, oats, rye, barley and other grains. Gluten is, like a poison to individuals with celiac disease, because, it damages the intestine severely., Features, i., ii., iii., iv., v., vi., , Diarrhea, Steatorrhea, Abdominal pain, Weight loss, Irritability, Depression.
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Chapter, , Large Intestine, , 42, , FUNCTIONAL ANATOMY, , , , PARTS OF LARGE INTESTINE, STRUCTURE OF WALL OF LARGE INTESTINE, , SECRETIONS OF LARGE INTESTINE, , , , COMPOSITION OF LARGE INTESTINAL JUICE, FUNCTIONS OF LARGE INTESTINAL JUICE, , FUNCTIONS OF LARGE INTESTINE, , , , , , , ABSORPTIVE FUNCTION, FORMATION OF FECES, EXCRETORY FUNCTION, SECRETORY FUNCTION, SYNTHETIC FUNCTION, , DIETARY FIBER, APPLIED PHYSIOLOGY, , , , , , DIARRHEA, CONSTIPATION, APPENDICITIS, ULCERATIVE COLITIS, , FUNCTIONAL ANATOMY OF, LARGE INTESTINE, , STRUCTURE OF WALL OF, LARGE INTESTINE, , Large intestine or colon extends from ileocecal valve up, to anus (Fig. 36.1)., , Wall of large intestine is formed by four layers of, structures like any other part of the gut., 1. Serous layer: It is formed by peritoneum, 2. Muscular layer: Smooth muscles of large intestine, are distributed in two layers, namely the outer, longitudinal layer and inner circular layer. The, longitudinal muscle fibers of large intestine are, arranged in the form of three long bands called, tenia coli. The length of the tenia coli is less when, compared to the length of large intestine. Because, of this, the large intestine is made into series of, pouches called haustra, , PARTS OF LARGE INTESTINE, Large intestine is made up of the following parts:, 1. Cecum with appendix, 2. Ascending colon, 3. Transverse colon, 4. Descending colon, 5. Sigmoid colon or pelvic colon, 6. Rectum, 7. Anal canal.
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Chapter 42 t Large Intestine 267, 3. Submucus layer: It is not well developed in large, intestine, 4. Mucus layer: The crypts of Leiberkühn are present, in mucosa of large intestine. But the villi, which are, present in mucus membrane of small intestine, are, absent in the large intestine. Only mucus-secreting, glands are present in the mucosa of large intestine., , SECRETIONS OF LARGE INTESTINE, Large intestinal juice is a watery fluid with pH of 8.0., COMPOSITION OF LARGE INTESTINAL JUICE, Large intestinal juice contains 99.5% of water and 0.5%, of solids (Fig. 42.1). Digestive enzymes are absent and, concentration of bicarbonate is high in large intestinal, juice., , FUNCTIONS OF LARGE INTESTINE, 1. ABSORPTIVE FUNCTION, Large intestine plays an important role in the absorption, of various substances such as:, i. Water, ii. Electrolytes, iii. Organic substances like glucose, iv. Alcohol, v. Drugs like anesthetic agents, sedatives and, steroids., 2. FORMATION OF FECES, After the absorption of nutrients, water and other, substances, the unwanted substances in the large, intestine form feces. This is excreted out., , FUNCTIONS OF LARGE INTESTINAL JUICE, Neutralization of Acids, Strong acids formed by bacterial action in large intestine, are neutralized by the alkaline nature of large intestinal, juice. The alkalinity of this juice is mainly due to the, presence of large quantity of bicarbonate., Lubrication Activity, Mucin present in the secretion of large intestine lubricates the mucosa of large intestine and the bowel, contents, so that, the movement of bowel is facilitated., Mucin also protects the mucus membrane of, large intestine by preventing the damage caused by, mechanical injury or chemical substances., , 3. EXCRETORY FUNCTION, Large intestine excretes heavy metals like mercury,, lead, bismuth and arsenic through feces., 4. SECRETORY FUNCTION, Large intestine secretes mucin and inorganic substances, like chlorides and bicarbonates., 5. SYNTHETIC FUNCTION, Bacterial flora of large intestine synthesizes folic acid,, vitamin B12 and vitamin K. By this function, large, intestine contributes in erythropoietic activity and blood, clotting mechanism., , DIETARY FIBER, , FIGURE 42.1: Composition of large intestinal juice, , Dietary fiber or roughage is a group of food particles, which pass through stomach and small intestine without, being digested and reach the large intestine unchanged., Other nutritive substances of food are digested and, absorbed before reaching large intestine., Characteristic feature of dietary fiber is that it is, not hydrolyzed by digestive enzymes. So, it escapes, digestion in small intestine and passes to large intestine., It provides substrate for microflora of large intestine and, increases the bacterial mass. The anaerobic bacteria,, in turn, degrade the fermentable components of the, fiber. Thus, in large intestine, some of the components, of fiber are broken down and absorbed and remaining, components are excreted through feces.
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268 Section 4 t Digestive System, Components of Dietary Fiber, Major components of dietary fiber are cellulose,, hemicelluloses, D-glucans, pectin, lignin and gums., Cellulose, hemicelluloses and pectin are partially, degradable, while other components are indigestible., Dietary fiber also contains minerals, antioxidants and, other chemicals that are useful for health., Sources of Dietary Fiber, Sources of dietary fiber are fruits, vegetables, cereals,, bread and wheat grain (particularly its outer layer)., Significance of Dietary Fiber, Diet with high dietary fiber has health benefits since, dietary fiber:, 1. Delays emptying of stomach, 2. Increases formation of bulk and soft feces and, eases defecation, 3. Contains substances such as antioxidants and other, useful substances., When high dietary fiber food is taken, other foods,, which may cause some diseases may be decreased in, quantity or completely excluded from diet. Diet with high, fiber content tends to be low in energy and it may be, useful in reducing the body weight. Some components, of dietary fiber also reduce blood cholesterol level and, thereby decrease the risk for coronary heart disease, and gallstones., Dietary fiber is suggested for treating or to prevent, constipation and bowel syndrome. It is also useful in, treatment of some disorders such as diabetics, cancer,, ulcer, etc., , APPLIED PHYSIOLOGY, DIARRHEA, Diarrhea is the frequent and profuse discharge of, intestinal contents in loose and fluid form. It occurs due, to the increased movement of intestine. It may be acute, or chronic., , 1. Dietary abuse: Diarrhea is caused by intake of, contaminated water or food, artificial sweeteners, found in food, spicy food, etc., 2. Food intolerance: Acute diarrhea is caused mainly, by indigestion of food substances, particularly, lactose, a sugar present in milk and milk products, may not be digested easily, 3. Infections by:, i. Bacteria such as Escherichia coli, Salmonella,, Shigella, etc., ii. Viruses like rotavirus, hepatitis virus, etc., iii. Parasites like Entamoeba histolytica, Giardia, lamblia, etc., 4. Reaction to medicines such as:, i. Antibiotics, ii. Antihypertensive drugs, iii. Antacids containing magnesium, iv. Laxatives, 5. Intestinal diseases: Chronic diarrhea occurs during, inflammation of intestine, irritable bowel syndrome, and abnormal motility of the intestine., Features, Severe diarrhea results in loss of excess water and, electrolytes. This leads to dehydration and electrolyte, imbalance. Chronic diarrhea results in hypokalemia, and metabolic acidosis. Other features of diarrhea are, abdominal pain, nausea and bloating (a condition in, which the subject feels the abdomen full and tight due, to excess intestinal gas)., CONSTIPATION, Failure of voiding of feces, which produces discomfort is, known as constipation. It is due to the lack of movements, necessary for defecation (Chapter 43). Due to the, absence of mass movement in colon, feces remain in, the large intestine for a long time, resulting in absorption, of fluid. So the feces become hard and dry., Causes, , Causes, Normally, when digested food passes through colon,, large portion of fluid is absorbed and only a semisolid, stool remains. In diarrhea, the fluid is not absorbed, sufficiently, resulting in watery bowel discharge. Acute, diarrhea may be caused by temporary problems like, infection and chronic diarrhea may be due to disorders, of intestinal mucosa. Thus, the general causes of, diarrhea are:, , 1. Dietary causes, Lack of fiber or lack of liquids in diet causes, constipation., 2. Irregular bowel habit, Irregular bowel habit is most common cause for, constipation. It causes constipation by inhibiting the, normal defecation reflexes.
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Chapter 42 t Large Intestine 269, 3. Spasm of sigmoid colon, Spasm in the sigmoid colon (spastic colon) prevents its, motility, resulting in constipation., 4. Diseases, Constipation is common in many types of diseases., 5. Dysfunction of myenteric plexus, in large intestine – megacolon, Megacolon is the condition characterized by distension, and hypertrophy of colon, associated with constipation., It is caused by the absence or damage of ganglionic, cells in myenteric plexus, which causes dysfunction, of myenteric plexus. It leads to accumulation of large, quantity of feces in colon. The colon is distended to a, diameter of 4 to 5 inch. It also results in hypertrophy of, colon. Congenital development of megacolon is called, , lower right side of the abdomen. It becomes severe, within 6 to 12 hours, 2. Nausea, 3. Vomiting, 4. Constipation or diarrhea, 5. Difficulty in passing gas, 6. Low fever, 7. Abdominal swelling, 8. Loss of appetite., If not treated immediately, the appendix may rupture, and the inflammation will spread to the whole body,, leading to severe complications, sometimes even death., Therefore, the treatment of appendicitis is considered, as an emergency., Usual standard treatment for appendicitis is, appendectomy (surgical removal of appendix)., , Hirschsprung disease., , ULCERATIVE COLITIS, , 6. Drugs, , Ulcerative colitis is an inflammatory bowel disease, (IBD), characterized by the inflammation and ulcerative, aberrations in the wall of the large intestine. It is also, known as colitis or proctitis. Rectum and lower part of, the colon are commonly affected. Sometimes, the entire, colon is affected., Ulcerative colitis can occur at any age. More, commonly, it affects people in the age group of 15 to 30, years. Rarely it affects 50 to 70 years old people., , The drugs like diuretics, pain relievers (narcotics),, antihypertensive drugs (calcium channel blockers),, antiparkinson drugs, antidepressants and the anticonvulsants cause constipation., APPENDICITIS, Inflammation of appendix is known as appendicitis., Appendix is a small, worm-like appendage, projecting, from cecum of ascending colon. It is situated on the, lower right side of the abdomen., Appendix does not have any function in human, beings. But, it can create major problems when diseased., Appendicitis can develop at any age. However, it is very, common between 10 and 30 years of age., Causes, The cause for appendicitis is not known. It may occur by, bacterial or viral infection. It also occurs during blockage, of connection between appendix and large intestine by, feces, foreign body or tumor., Features, 1. Main symptom of appendicitis is the pain, which, starts around the umbilicus and then spreads to the, , Cause, Exact cause for ulcerative colitis is not known. However,, it is believed that the interaction between the immune, system and viral or bacterial infection causes this, disease., Features, 1., 2., 3., 4., 5., 6., 7., 8., 9., , Abdominal pain, Diarrhea with blood in the stools, Early fatigue, Loss of appetite and weight, Arthritis and osteoporosis, Eye inflammation, Liver diseases like hepatitis, cirrhosis, etc., Skin rashes, Anemia.
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Movements of, Gastrointestinal Tract, , , , , , , , , , , Chapter, , 43, , MASTICATION, DEGLUTITION, MOVEMENTS OF STOMACH, FILLING AND EMPTYING OF STOMACH, VOMITING, MOVEMENTS OF SMALL INTESTINE, MOVEMENTS OF LARGE INTESTINE, DEFECATION, EVACUATION OF GASES FROM GASTROINTESTINAL TRACT, , MASTICATION, , CONTROL OF MASTICATION, , Mastication or chewing is the first mechanical process, in the gastrointestinal (GI) tract, by which the food, substances are torn or cut into small particles and, crushed or ground into a soft bolus., , Action of mastication is mostly a reflex process. It is, carried out voluntarily also. The center for mastication, is situated in medulla and cerebral cortex. Muscles of, mastication are supplied by mandibular division of 5th, cranial (trigeminal) nerve., , Significances of mastication, 1. Breakdown of foodstuffs into smaller particles, 2. Mixing of saliva with food substances thoroughly, 3. Lubrication and moistening of dry food by saliva, so, that the bolus can be easily swallowed, 4. Appreciation of taste of the food., MUSCLES AND THE MOVEMENTS, OF MASTICATION, Muscles of Mastication, 1., 2., 3., 4., , Masseter muscle, Temporal muscle, Pterygoid muscles, Buccinator muscle., , Movements of Mastication, 1. Opening and closure of mouth, 2. Rotational movements of jaw, 3. Protraction and retraction of jaw., , DEGLUTITION, Definition, Deglutition or swallowing is the process by which food, moves from mouth into stomach., Stages of Deglutition, Deglutition occurs in three stages:, I. Oral stage, when food moves from mouth to, pharynx, II. Pharyngeal stage, when food moves from, pharynx to esophagus, III. Esophageal stage, when food moves from, esophagus to stomach., ORAL STAGE OR FIRST STAGE, Oral stage of deglutition is a voluntary stage. In this, stage, the bolus from mouth passes into pharynx by, means of series of actions.
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Chapter 43 t Movements of Gastrointestinal Tract 271, Sequence of Events during Oral Stage, 1. Bolus is placed over postero-dorsal surface of the, tongue. It is called the preparatory position, 2. Anterior part of tongue is retracted and depressed., 3. Posterior part of tongue is elevated and retracted, against the hard palate. This pushes the bolus, backwards into the pharynx, 4. Forceful contraction of tongue against the palate, produces a positive pressure in the posterior part of, oral cavity. This also pushes the food into pharynx, (Fig. 43.1)., PHARYNGEAL STAGE OR SECOND STAGE, Pharyngeal stage is an involuntary stage. In this stage,, the bolus is pushed from pharynx into the esophagus., Pharynx is a common passage for food and air. It, divides into larynx and esophagus. Larynx lies anteriorly, and continues as respiratory passage. Esophagus lies, behind the larynx and continues as GI tract. Since, pharynx communicates with mouth, nose, larynx and, esophagus, during this stage of deglutition, bolus from, the pharynx can enter into four paths:, 1. Back into mouth, 2. Upward into nasopharynx, 3. Forward into larynx, 4. Downward into esophagus., However, due to various coordinated movements,, bolus is made to enter only the esophagus. Entrance of, bolus through other paths is prevented as follows:, 1. Back into Mouth, Return of bolus back into the mouth is prevented by:, i. Position of tongue against the soft palate (roof, of the mouth), ii. High intraoral pressure, developed by the, movement of tongue., 2. Upward into Nasopharynx, Movement of bolus into the nasopharynx from pharynx, is prevented by elevation of soft palate along with its, extension called uvula., 3. Forward into Larynx, Movement of bolus into the larynx is prevented by the, following actions:, i. Approximation of the vocal cords, ii. Forward and upward movement of larynx, iii. Backward movement of epiglottis to seal the, opening of the larynx (glottis), , iv. All these movements arrest respiration for a few, seconds. It is called deglutition apnea., Deglutition apnea, Apnea refers to temporary arrest of breathing. Deglutition, apnea or swallowing apnea is the arrest of breathing, during pharyngeal stage of deglutition., 4. Entrance of Bolus into Esophagus, As the other three paths are closed, the bolus has to, pass only through the esophagus. This occurs by the, combined effects of various factors:, i. Upward movement of larynx stretches the, opening of esophagus, ii. Simultaneously, upper 3 to 4 cm of esophagus, relaxes. This part of esophagus is formed by the, cricopharyngeal muscle and it is called upper, esophageal sphincter or pharyngoesophageal, sphincter, , iii. At the same time, peristaltic contractions start in, the pharynx due to the contraction of pharyngeal, muscles, iv. Elevation of larynx also lifts the glottis away from, the food passage., All the factors mentioned above act together so, that, bolus moves easily into the esophagus. The whole, process takes place within 1 to 2 seconds and this, process is purely involuntary., ESOPHAGEAL STAGE OR THIRD STAGE, Esophageal stage is also an involuntary stage. In, this stage, food from esophagus enters the stomach., Esophagus forms the passage for movement of bolus, from pharynx to the stomach. Movements of esophagus, are specifically organized for this function and the, movements are called peristaltic waves. Peristalsis, means a wave of contraction, followed by the wave, of relaxation of muscle fibers of GI tract, which travel, in aboral direction (away from mouth). By this type of, movement, the contents are propelled down along the, GI tract., When bolus reaches the esophagus, the peristaltic, waves are initiated. Usually, two types of peristaltic, contractions are produced in esophagus., 1. Primary peristaltic contractions, 2. Secondary peristaltic contractions., 1. Primary Peristaltic Contractions, When bolus reaches the upper part of esophagus, the, peristalsis starts. This is known as primary peristalsis.
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272 Section 4 t Digestive System, , FIGURE 43.1: Stages of deglutition. A. Preparatory stage; B. Oral stage; C. Pharyngeal stage; D. Esophageal stage., , After origin, the peristaltic contractions pass down, through the rest of the esophagus, propelling the bolus, towards stomach., Pressure developed during the primary peristaltic, contractions is important to propel the bolus. Initially,, the pressure becomes negative in the upper part of, esophagus. This is due to the stretching of the closed, esophagus by the elevation of larynx. But immediately,, the pressure becomes positive and increases up to 10, to 15 cm of H2O., 2. Secondary Peristaltic Contractions, If the primary peristaltic contractions are unable to propel, the bolus into the stomach, the secondary peristaltic, contractions appear and push the bolus into stomach., Secondary peristaltic contractions are induced by, the distention of upper esophagus by the bolus. After, origin, these contractions pass down like the primary, contractions, producing a positive pressure., Role of Lower Esophageal Sphincter, Distal 2 to 5 cm of esophagus acts like a sphincter, and it is called lower esophageal sphincter. It is, constricted always. When bolus enters this part of the, esophagus, this sphincter relaxes so that the contents, enter the stomach. After the entry of bolus into the, stomach, the sphincter constricts and closes the lower, end of esophagus. The relaxation and constriction of, sphincter occur in sequence with the arrival of peristaltic, contractions of esophagus., , DEGLUTITION REFLEX, Though the beginning of swallowing is a voluntary, act, later it becomes involuntary and is carried out by, a reflex action called deglutition reflex. It occurs during, the pharyngeal and esophageal stages., Stimulus, When the bolus enters the oropharyngeal region, the, receptors present in this region are stimulated., Afferent Fibers, Afferent impulses from the oropharyngeal receptors, pass via the glossopharyngeal nerve fibers to the, deglutition center., Center, Deglutition center is at the floor of the fourth ventricle in, medulla oblongata of brain., Efferent Fibers, Impulses from deglutition center travel through, glossopharyngeal and vagus nerves (parasympathetic, motor fibers) and reach soft palate, pharynx and, esophagus. The glossopharyngeal nerve is concerned, with pharyngeal stage of swallowing. The vagus nerve, is concerned with esophageal stage., Response, The reflex causes upward movement of soft palate, to, close nasopharynx and upward movement of larynx,
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Chapter 43 t Movements of Gastrointestinal Tract 273, to close respiratory passage so that bolus enters the, esophagus. Now the peristalsis occurs in esophagus,, pushing the bolus into stomach., APPLIED PHYSIOLOGY, , Types of movements in stomach, 1. Hunger contractions, 2. Receptive relaxation, 3. Peristalsis., , 1. Dysphagia, , 1. HUNGER CONTRACTIONS, , Dysphagia means difficulty in swallowing., , Hunger contractions are the movements of empty, stomach. These contractions are related to the sensations of hunger., Hunger contractions are the peristaltic waves, superimposed over the contractions of gastric smooth, muscle as a whole. This type of peristaltic waves is, different from the digestive peristaltic contractions., The digestive peristaltic contractions usually occur in, body and pyloric parts of the stomach. But, peristaltic, contractions of empty stomach involve the entire, stomach. Hunger contractions are of three types:, , Causes of dysphagia, i. Mechanical obstruction of esophagus due to, tumor, strictures, diverticular hernia (out pouching of the wall), etc., ii. Decreased movement of esophagus due to, neurological disorders such as parkinsonism, iii. Muscular disorders leading to difficulty in swallowing during oral stage or esophageal stage., 2. Esophageal Achalasia or Achalasia Cardia, Esophageal achalasia or achalasia cardia is a neuromuscular disease, characterized by accumulation of, food substances in the esophagus preventing normal, swallowing. It is due to the failure of lower esophageal, (cardiac) sphincter to relax during swallowing. The accumulated food substances cause dilatation of esophagus., Features of esophageal achalasia, i., ii., iii., iv., , Dysphagia, Chest pain, Weight loss, Cough., , 3. Gastroesophageal Reflux Disease (GERD), GERD is a disorder characterized by regurgitation, of acidic gastric content through esophagus. The, regurgitated gastric content flows into pharynx or mouth., Regurgitation is due to the weakness or incompetence, (failure to constrict) of lower esophageal sphincter., Features of GERD, i. Heart burn or pyrosis (painful burning sensation, in chest due to regurgitation of acidic gastric, content into esophagus), ii. Esophagitis (inflammation of esophagus), iii. Dysphagia, iv. Cough and change of voice, v. Esophageal ulcers or cancer (in chronic cases)., , MOVEMENTS OF STOMACH, Activities of smooth muscles of stomach increase during, gastric digestion (when stomach is filled with food) and, when the stomach is empty., , Type I Hunger Contractions, Type I hunger contractions are the first contractions, to appear in the empty stomach, when the tone of the, gastric muscles is low. Each contraction lasts for about, 20 seconds. The interval between contractions is about, 3 to 4 seconds. Tone of the muscles does not increase, between contractions. Pressure produced by these, contractions is about 5 cm of H2O., Type II Hunger Contractions, Type II hunger contractions appear when the tone of, stomach is stronger. Tone increases in stomach if food, intake is postponed, even after the appearance of the, type I contractions. Each of the type II contractions, lasts for 20 seconds like type I contractions. But the, pause between the contractions is decreased. Pressure, produced by these contractions is 10 to 15 cm of H2O., Type III Hunger Contractions, Type III hunger contractions are like incomplete tetanus., These contractions appear when the hunger becomes, severe and the tone increases to a great extent. Type III, hunger contractions are rare in man as the food is taken, usually before the appearance of these contractions., These contractions last for 1 to 5 minutes. The pressure, produced by these contractions increases to 10 to 20, cm of H2O., When the stomach is empty, the type I contractions, occur first, followed by type II contractions. If food intake, is still postponed, then type III contractions appear and, as soon as food is consumed, hunger contractions, disappear.
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274 Section 4 t Digestive System, 2. RECEPTIVE RELAXATION, , Chyme, , Receptive relaxation is the relaxation of the upper portion of the stomach when bolus enters the stomach from, esophagus. It involves the fundus and upper part of the, body of stomach. Its significance is to accommodate the, food easily, without much increase in pressure inside, the stomach. This process is called accommodation of, stomach., , Chyme is the semisolid mass of partially digested food, that is formed in the stomach. It is acidic in nature., Acid chyme is emptied from stomach into the intestine, slowly, with the help of peristaltic contractions. It takes, about 3 to 4 hours for emptying of the chyme. This slow, emptying is necessary to facilitate the final digestion and, maximum (about 80%) absorption of the digested food, materials from small intestine. Gastric emptying occurs, due to the peristaltic waves in the body and pyloric part, of the stomach and simultaneous relaxation of pyloric, sphincter., Gastric emptying is influenced by various factors of, the gastric content and food., , 3. PERISTALSIS, When food enters the stomach, the peristaltic contraction or peristaltic wave appears with a frequency of 3, per minute. It starts from the lower part of the body of, stomach, passes through the pylorus till the pyloric, sphincter., , Initially, the contraction appears as a slight indentation on the greater and lesser curvatures and travels, towards pylorus. The contraction becomes deeper while, traveling. Finally, it ends with the constriction of pyloric, sphincter. Some of the waves disappear before reaching, the sphincter. Each peristaltic wave takes about one, minute to travel from the point of origin to the point of, ending., This type of peristaltic contraction is called digestive, peristalsis because it is responsible for the grinding of, food particles and mixing them with gastric juice for, digestive activities., , FILLING AND EMPTYING OF STOMACH, FILLING OF STOMACH, While taking food, it arranges itself in the stomach in, different layers. The first eaten food is placed against, the greater curvature in the fundus and body of the, stomach. The successive layers of food particles lie, nearer, the lesser curvature, until the last portion of, food eaten lies near the upper end of lesser curvature,, adjacent to cardiac sphincter., The liquid remains near the lesser curvature and, flows towards the pyloric end of the stomach along a, V-shaped groove. This groove is formed by the smooth, muscle and it is called magenstrasse. But, if a large, quantity of fluid is taken, it flows around the entire food, mass and is distributed over the interior part of stomach,, between wall of the stomach and food mass., EMPTYING OF STOMACH, Gastric emptying is the process by which the chyme, from stomach is emptied into intestine. Food that is, swallowed enters the stomach and remains there for, about 3 hours. During this period, digestion takes place., Partly digested food in stomach becomes the chyme., , Factors Affecting Gastric Emptying, 1. Volume of gastric content, For any type of meal, gastric emptying is directly, proportional to the volume. If the content of stomach, is more, a large amount is emptied into the intestine, rapidly., 2. Consistency of gastric content, Emptying of the stomach depends upon consistency, (degree of density) of the contents. Liquids, particularly, the inert liquids like water leave the stomach rapidly., Solids leave the stomach only after being converted, into fluid or semifluid. Undigested solid particles are not, easily emptied., 3. Chemical composition, Chemical composition of the food also plays an important, role in the emptying of the stomach. Carbohydrates are, emptied faster than the proteins. Proteins are emptied, faster than the fats. Thus, the fats are emptied very, slowly., 4. pH of the gastric content, Gastric emptying is directly proportional to pH of the, chyme., 5. Osmolar concentration of gastric content, Gastric content which is isotonic to blood, leaves the, stomach rapidly than the hypotonic or hypertonic, content., REGULATION OF GASTRIC EMPTYING, Gastric emptying is regulated by nervous and hormonal, factors.
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Chapter 43 t Movements of Gastrointestinal Tract 275, Nervous Factor, Nervous factor which regulates the emptying of stomach, is the enterogastric reflex., Enterogastric Reflex, Enterogastric reflex is the reflex that inhibits gastric, emptying. It is elicited by the presence of chyme in, the duodenum, which prevents further emptying of, stomach., Mechanism of enterogastric reflex, 1. Presence of chyme in duodenum causes generation, of nerve impulses which are transmitted to stomach, by the intrinsic nerve fibers of GI tract. After reaching, the stomach, these impulses inhibit emptying., 2. Impulses from duodenum pass via extrinsic, sympathetic fibers to stomach and inhibit emptying., 3. Some impulses from duodenum travel through, afferent vagal fibers to the brainstem. Normally,, brainstem neurons send excitatory impulses to, stomach through efferent vagal fibers and stimulate, gastric emptying. However, the impulses from, duodenum inhibit these brainstem neurons and, thereby inhibit gastric emptying., Factors which initiate enterogastric reflex, 1., 2., 3., 4., 5., , Duodenal distension, Irritation of the duodenal mucosa, Acidity of the chyme, Osmolality of the chyme, Breakdown products of proteins and fats., , Hormonal Factors, When an acid chyme enters the duodenum, the, duodenal mucosa releases some hormones which, enter the stomach through blood and inhibit the motility, of stomach., Hormones inhibiting gastric motility and emptying, 1., 2., 3., 4., 5., 6., , Vasoactive intestinal peptide (VIP), Gastric inhibitory peptide (GIP), Secretin, Cholecystokinin, Somatostatin, Peptide YY., , APPLIED PHYSIOLOGY – ABNORMAL, GASTRIC EMPTYING, 1. Gastric Dumping Syndrome, Gastric dumping syndrome or rapid gastric emptying is, the condition characterized by series of upper abdominal, , symptoms. It is due to the rapid or quick dumping, of undigested food from stomach into the jejunum., It occurs in patients following partial gastrectomy, (removal of stomach) or gastroenterostomy (gastric, bypass surgery). The rapid gastric emptying may begin, immediately after taking meals (early dumping) or about, few hours after taking meals (late dumping)., Causes, i. Gastric surgery., ii. Zollinger-Ellison syndrome (rare disorder due to, severe peptic ulcer and gastrin-secreting tumor, in pancreas)., Symptoms of early dumping, i. Nausea and vomiting, ii. Bloating (increase in abdominal volume with, feeling of abdominal fullness and tightness), iii. Diarrhea, iv. Sweating and weakness, v. Fatigue and dizziness, vi. Fainting and palpitations (sensation of heart, beat)., Symptoms of late dumping, i. Hypoglycemia, ii. Sweating and weakness, iii. Dizziness., 2. Gastroparesis, Gastroparesis is a chronic disorder characterized, by delayed gastric emptying. It usually occurs as a, secondary disorder, precipitated by a primary cause., Causes, i., ii., iii., iv., v., vi., , Diabetes mellitus, Postsurgical complications, Motility disorder, Gastric infection, Metabolic and endocrine disorder, Decrease in myenteric ganglia (rare)., , Symptoms, i. Early satiety (feeling full with small quantity of, food), ii. Nausea, iii. Vomiting, iv. Bloating, v. Upper abdominal discomfort.
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276 Section 4 t Digestive System, , VOMITING, Vomiting or emesis is the abnormal emptying of stomach, and upper part of intestine through esophagus and, mouth., CAUSES OF VOMITING, 1., 2., 3., 4., 5., 6., 7., 8., 9., 10., 11., , Presence of irritating contents in GI tract, Mechanical stimulation of pharynx, Pregnancy, Excess intake of alcohol, Nauseating sight, odor or taste, Unusual stimulation of labyrinthine apparatus, as in, the case of sea sickness, air sickness, car sickness, or swinging, Abnormal stimulation of sensory receptors in other, organs like kidney, heart, semicircular canals or, uterus, Drugs like antibiotics, opiates, etc., Any GI disorder, Acute infection like urinary tract infection, influenza,, etc., Metabolic disturbances like carbohydrate starvation, and ketosis (pregnancy), uremia, ketoacidosis, (diabetes) and hypercalcemia., , MECHANISM OF VOMITING, Nausea, Vomiting is always preceded by nausea. Nausea is, unpleasant sensation which induces the desire for, vomiting. It is characterized by secretion of large amount, of saliva containing more amount of mucus., Retching, Strong involuntary movements in the GI tract which, start even before actual vomiting. These movements, intensify the feeling of vomiting. This condition is called, retching (try to vomit) and vomiting occurs few minutes, after this., Act of Vomiting, Act of vomiting involves series of movements that takes, place in GI tract., Sequence of events:, 1. Beginning of antiperistalsis, which runs from ileum, towards the mouth through the intestine, pushing, the intestinal contents into the stomach within few, minutes. Velocity of the antiperistalsis is about 2 to, 3 cm/second, 2. Deep inspiration followed by temporary cessation of, breathing, , 3. Closure of glottis, 4. Upward and forward movement of larynx and hyoid, bone, 5. Elevation of soft palate, 6. Contraction of diaphragm and abdominal muscles, with a characteristic jerk, resulting in elevation of, intra-abdominal pressure, 7. Compression of the stomach between diaphragm, and abdominal wall leading to rise in intragastric, pressure, 8. Simultaneous relaxation of lower esophageal sphincter, esophagus and upper esophageal sphincter, 9. Forceful expulsion of gastric contents (vomitus), through esophagus, pharynx and mouth., Movements during act of vomiting throw the vomitus, (materials ejected during vomiting) to the exterior, through mouth. Some of the movements play important, roles by preventing the entry of vomitus through other, routes and thereby prevent the adverse effect of the, vomitus on many structures., Such movements are:, 1. Closure of glottis and cessation of breathing, prevents entry of vomitus into the lungs, 2. Elevation of soft palate prevents entry of vomitus, into the nasopharynx, 3. Larynx and hyoid bone move upward and forward, and are placed in this position rigidly. This causes, the dilatation of throat, which allows free exit of, vomitus., VOMITING REFLEX, Vomiting is a reflex act. Sensory impulses for vomiting, arise from the irritated or distended part of GI tract or, other organs and are transmitted to the vomiting center, through vagus and sympathetic afferent fibers., Vomiting center is situated bilaterally in medulla, oblongata near the nucleus tractus solitarius., Motor impulses from the vomiting center are, transmitted through V, VII, IX, X and XII cranial nerves, to the upper part of GI tract; and through spinal nerves, to diaphragm and abdominal muscles., Center for Vomiting during Motion Sickness, and Vomiting Induced by Drugs, Center for vomiting during motion sickness and vomiting, induced by drugs such as morphine, apomorphine, etc., is on the floor of fourth ventricle. This area is called, chemoreceptor trigger zone. During motion sickness,, the afferent impulses from vestibular apparatus reach, vomiting center through this zone.
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Chapter 43 t Movements of Gastrointestinal Tract 277, Center for Psychic-stimuli-induced Vomiting, Center for vomiting due to psychic stimuli such as, nauseating odor, sight or noise is in cerebral cortex., , MOVEMENTS OF SMALL INTESTINE, Movements of small intestine are essential for mixing, the chyme with digestive juices, propulsion of food and, absorption., Types of Movements of Small Intestine, Movements of small intestine are of four types:, 1. Mixing movements:, i. Segmentation movements, ii. Pendular movements., 2. Propulsive movements:, i. Peristaltic movements, ii. Peristaltic rush., 3. Peristalsis in fasting – migrating motor complex, 4. Movements of villi., 1. MIXING MOVEMENTS, Mixing movements of small intestine are responsible, for proper mixing of chyme with digestive juices such, as pancreatic juice, bile and intestinal juice. The, mixing movements of small intestine are segmentation, contractions and pendular movements., , clock. Small portions of intestine (loops) sweep forward, and backward or upward and downward. It is a type of, mixing movement, noticed only by close observation., It helps in mixing of chyme with digestive juices., 2. PROPULSIVE MOVEMENTS, Propulsive movements are the movements of small, intestine which push the chyme in the aboral direction, through intestine. The propulsive movements are, peristaltic movements and peristaltic rush., i. Peristaltic Movements, Peristalsis is defined as the wave of contraction, followed by wave of relaxation of muscle fibers. In GI, tract, it always travels in aboral direction. Stimulation of, smooth muscles of intestine initiates the peristalsis. It, travels from point of stimulation in both directions. But, under normal conditions, the progress of contraction in, an oral direction is inhibited quickly and the contractions, disappear. Only the contraction that travels in an aboral, direction persists., Starling’s law of intestine, Depending upon the direction of the peristalsis, ‘Law of, intestine’ was put forth by Starling., According to the law of intestine, the response of, the intestine for a local stimulus consists of a contraction, , i. Segmentation Contractions, Segmentation contractions are the common type of, movements of small intestine, which occur regularly or, irregularly, but in a rhythmic fashion. So, these movements, are also called rhythmic segmentation contractions., The contractions occur at regularly spaced intervals, along a section of intestine. The segment of the intestine, involved in each contraction is about 1 to 5 cm long., The segments of intestine in between the contracted, segments are relaxed. The length of the relaxed, segments is same as that of the contracted segments., These alternate segments of contraction and relaxation, give appearance of rings, resembling the chain of, sausages., After sometime, the contracted segments are, relaxed and the relaxed segments are contracted (Fig., 43.2). Therefore, the segmentation contractions chop, the chyme many times. This helps in mixing of chyme, with digestive juices., ii. Pendular Movement, Pendular movement is the sweeping movement of small, intestine, resembling the movements of pendulum of, , FIGURE 43.2: Movements of small intestine
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278 Section 4 t Digestive System, of smooth muscle above and relaxation below the, stimulated area., Peristaltic contractions start at any part of the, intestine and travel towards anal end, at a velocity of, 1 to 2 cm/sec. The contractions are always weak and, usually disappear after traveling for few centimeter., Because of this, the average movement of chyme, through small intestine is very slow and the average, velocity of movement of the chyme is less than 1 cm/, sec. So, the chyme requires several hours to travel from, duodenum to the end of small intestine., Peristaltic waves in small intestine increase to a, great extent immediately after a meal. This is because of, gastroenteric reflex, which is initiated by the distention, of stomach. Impulses for this reflex are transmitted from, stomach along the wall of the intestine via myenteric, plexus., , 4. MOVEMENTS OF VILLI, , ii. Peristaltic Rush, , MOVEMENTS OF LARGE INTESTINE, , Sometimes, the small intestine shows a powerful peristaltic contraction. It is caused by excessive irritation of, intestinal mucosa or extreme distention of the intestine., This type of powerful contraction begins in duodenum, and passes through entire length of small intestine and, reaches the ileocecal valve within few minutes. This is, called peristaltic rush or rush waves., Peristaltic rush sweeps the contents of intestine into, the colon. Thus, it relieves the small intestine off either, irritants or excessive distention., , Usually, the large intestine shows sluggish movements., Still, these movements are important for mixing,, propulsive and absorptive functions., , 3. PERISTALSIS IN FASTING –, MIGRATING MOTOR COMPLEX, Migrating motor complex is a type of peristaltic, contraction, which occurs in stomach and small intestine, during the periods of fasting for several hours. It is also, called migrating myoelectric complex. It is different, from the regular peristalsis because, a large portion of, stomach or intestine is involved in the contraction. The, contraction extends to about 20 to 30 cm of stomach or, intestine. This type of movement occurs once in every, 1½ to 2 hours., It starts as a moderately active peristalsis in the, body of stomach and runs through the entire length of, small intestine. It travels at a velocity of 6 to 12 cm/min., Thus, it takes about 10 minutes to reach the colon after, taking origin from the stomach., Significance of Peristalsis in Fasting, Migrating motor complex sweeps the excess digestive, secretions into the colon and prevents the accumulation, of the secretions in stomach and intestine. It also sweeps, the residual indigested materials into colon., , Intestinal villi also show movements simultaneously, along with intestinal movements. It is because of the, extension of smooth muscle fibers of the intestinal wall, into the villi., Movements of villi are shortening and elongation,, which occur alternatively and help in emptying lymph, from the central lacteal into the lymphatic system. The, surface area of villi is increased during elongation. This, helps absorption of digested food particles from the, lumen of intestine., Movements of villi are caused by local nervous, reflexes, which are initiated by the presence of chyme, in small intestine. Hormone secreted from the small, intestinal mucosa called villikinin is also believed to play, an important role in increasing the movements of villi., , Types of Movements of Large Intestine, Movements of large intestine are of two types:, 1. Mixing movements: Segmentation contractions, 2. Propulsive movements: Mass peristalsis., 1. MIXING MOVEMENTS –, SEGMENTATION CONTRACTIONS, Large circular constrictions, which appear in the colon,, are called mixing segmentation contractions. These, contractions occur at regular distance in colon. Length, of the portion of colon involved in each contraction is, nearly about 2.5 cm., 2. PROPULSIVE MOVEMENTS –, MASS PERISTALSIS, Mass peristalsis or mass movement propels the feces, from colon towards anus. Usually, this movement occurs, only a few times every day. Duration of mass movement, is about 10 minutes in the morning before or after, breakfast. This is because of the neurogenic factors, like gastrocolic reflex (see below) and parasympathetic, stimulation., , DEFECATION, Voiding of feces is known as defecation. Feces is formed, in the large intestine and stored in sigmoid colon. By the, influence of an appropriate stimulus, it is expelled out
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Chapter 43 t Movements of Gastrointestinal Tract 279, through the anus. This is prevented by tonic constriction, of anal sphincters, in the absence of the stimulus., DEFECATION REFLEX, Mass movement drives the feces into sigmoid or pelvic, colon. In the sigmoid colon, the feces is stored. The, desire for defecation occurs when some feces enters, rectum due to the mass movement. Usually, the desire, for defecation is elicited by an increase in the intrarectal, pressure to about 20 to 25 cm H2O., Usual stimulus for defecation is intake of liquid, like coffee or tea or water. But it differs from person to, person., Act of Defecation, Act of defecation is preceded by voluntary efforts like, assuming an appropriate posture, voluntary relaxation, of external sphincter and the compression of abdominal, contents by voluntary contraction of abdominal, muscles., Usually, the rectum is empty. During the development, of mass movement, the feces is pushed into rectum, and the defecation reflex is initiated. The process of, defecation involves the contraction of rectum and, relaxation of internal and external anal sphincters., Internal anal sphincter is made up of smooth muscle, and it is innervated by parasympathetic nerve fibers via, pelvic nerve. External anal sphincter is composed of, skeletal muscle and it is controlled by somatic nerve, fibers, which pass through pudendal nerve. Pudendal, nerve always keeps the external sphincter constricted, and the sphincter can relax only when the pudendal, nerve is inhibited., , nerve fibers of pelvic nerve. Motor impulses cause, strong contraction of descending colon, sigmoid colon, and rectum and relaxation of internal sphincter., Simultaneously, voluntary relaxation of external, sphincter occurs. It is due to the inhibition of pudendal, nerve, by impulses arising from cerebral cortex (Fig., 43.3)., CONSTIPATION, Constipation is the failure of voiding of feces. Refer, Chapter 42 for details., , EVACUATION OF GASES FROM, GASTROINTESTINAL TRACT, Normally, gas accumulates in the GI tract either because, of entrance of outside air or production of gases in the, body. Accordingly, the gases accumulated in GI tract are, classified into two groups:, 1. Exogenous gases, 2. Endogenous gases., , Gastrocolic Reflex, Gastrocolic reflex is the contraction of rectum, followed, by the desire for defecation caused by distention of, stomach by food. It is mediated by intrinsic nerve fibers, of GI tract., This reflex causes only a weak contraction of, rectum. But, it initiates defecation reflex., PATHWAY FOR DEFECATION REFLEX, When rectum is distended due to the entry of feces by, mass movement, sensory nerve endings are stimulated., Impulses from the nerve endings are transmitted via, afferent fibers of pelvic nerve to the defecation center,, situated in sacral segments (center) of spinal cord., The center in turn, sends motor impulses to the, descending colon, sigmoid colon and rectum via efferent, , FIGURE 43.3: Defecation reflex. Afferent and efferent fibers, of the reflex pass through pelvic (parasympathetic) nerve., Voluntary control of defecation is by pudendal (somatic) nerve., Defecation center is in the sacral segments of spinal cord
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280 Section 4 t Digestive System, 1. Exogenous Gases, Exogenous gases form about 90% of accumulated gases., These gases enter the GI tract either by swallowing, through mouth or drinking carbonated beverages., 2. Endogenous Gases, Endogenous gases form about 10% of accumulated, gases. These gases are produced by digestion of food, stuffs and interaction between bacteria and food stuffs, in the intestine., EVACUATION OF ACCUMULATED GASES, Evacuation of accumulated gases usually occurs by two, processes:, 1. Belching, 2. Flatulence., BELCHING, Belching is the process by which the gas accumulated, in stomach is expelled through mouth. It is also called, burping. It occurs because of inflation (distention) of, stomach by swallowed air. The distention of the stomach, causes abdominal discomfort and the belching expels, the air and relieves the discomfort., Most of the gas accumulated in stomach is expelled, through mouth. Only a small amount enters the intestine., Causes for Accumulation of Gases in Stomach, 1. Aerophagia: Swallowing large amounts of air due to, gulping the food or drink too rapidly, 2. Drinking carbonated beverages, 3. During some emotional conditions like anxiety lot of, air enters the stomach through mouth., Act of Belching, Belching is not a simple act and it requires the, coordination of several activities such as:, 1. Closure of larynx, which prevents entry of liquid or, food with the air from stomach into the lungs., 2. Elevation of larynx and relaxation of upper, esophageal sphincter. It allows exit of air through, esophagus more easily., , 3. Opening of lower esophageal sphincter., 4. Descent of diaphragm, which increases abdominal, pressure and decreases intrathoracic pressure., All these activities are responsible for the expulsion, of air from stomach to the exterior via esophagus., FLATULENCE, Flatulence is the production of a mixture of intestinal, gases. The mixture of gases is known as flatus (in, Latin, flatus = wind). Expulsion of flatus through anus, under pressure is called farting or passing gas. Farting, is associated with disagreeable odor (due to odorous, gases) and sound (due to vibration of anal sphincter)., Quantity of Flatus, Average flatus released by human is about 500 to 1500, mL per day, with 10 to 25 episodes throughout the day., Source of Gases in Intestine, Flatulence is the mixture of gases present in the intestine., Flatulence by swallowed air is rare., Common sources of gases in flatulence are:, 1. Bacterial action on undigested sugars and polysaccharides (e.g. starch, cellulose), 2. Digestion of some flatulence producing food stuffs, such as cheese, yeast in bread, oats, onion, beans,, cabbage, milk, etc., Constituents of Flatus, Major constituents of flatus:, 1. Swallowed non-odorous gases, i. Nitrogen (major constituent), ii. Oxygen, 2. Non-odorous gases produced by microbes, i. Methane, ii. Carbon dioxide, iii. Hydrogen, 3. Odorous materials such as, i. Low molecular weight fatty acids like butyric, acid, ii. Reduced sulfur compounds (hydrogen sulfide, and carbonyl sulfide).
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Gastrointestinal Hormones, , Chapter, , 44, , INTRODUCTION, CELLS SECRETING THE HORMONES, DESCRIPTION OF GASTROINTESTINAL HORMONES, , , , , , , , , , , , , , , , , , , GASTRIN, SECRETIN, CHOLECYSTOKININ, GLUCOSE-DEPENDENT INSULINOTROPIC HORMONE, VASOACTIVE INTESTINAL POLYPEPTIDE, GLUCAGON, GLICENTIN, GLUCAGON-LIKE POLYPEPTIDE-1, GLUCAGON-LIKE POLYPEPTIDE-2, SOMATOSTATIN, PANCREATIC POLYPEPTIDE, PEPTIDE YY, NEUROPEPTIDE Y, MOTILIN, SUBSTANCE P, GHRELIN, OTHER GASTROINTESTINAL HORMONES, , INTRODUCTION, , Neuroendocrine Cells or APUD Cells, , Gastrointestinal (GI) hormones are the hormones secreted, in GI tract. These hormones are polypeptides in nature, and belong to the family of local hormones (Chapter, 73). Major function of these hormones is to regulate the, secretory activities and motility of the GI tract., , Enteroendocrine cells which secrete hormones from, amines are known as amine precursor uptake and, decarboxylation cells (APUD cells) or neuroendocrine, cells. For the synthesis of a GI hormone, first a precursor, substance of an amine is taken up by these cells. Later,, this precursor substance is decarboxylated to form the, amine. From this amine, the hormone is synthesized., Because of the uptake of the amine precursor and, decarboxylation of this precursor substance, these cells, are called APUD cells. This type of cells is also present, in other parts of the body, particularly the brain, lungs, and the endocrine glands., , CELLS SECRETING THE HORMONES, Enteroendocrine Cells, Enteroendocrine cells are the hormone-secreting cells, in GI tract. These are the nerve cells and glandular, cells which are present in the gastric mucosa, intestinal, mucosa and the pancreatic cells.
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282 Section 4 t Digestive System, Enterochromaffin Cells, Enteroendocrine cells which secrete serotonin are called, enterochromaffin cells., , DESCRIPTION OF, GASTROINTESTINAL HORMONES, 1. GASTRIN, Gastrin is a peptide with 34 amino acid residues. It, is secreted mainly by the G cells of pyloric glands of, stomach. It is also secreted by TG cells in stomach,, duodenum and jejunum. In fetus, the islets of, Langerhans also secrete this hormone (Table 44.1)., , Gastrin is secreted from stomach during the gastric, (second) phase of gastric secretion and from small intestine, during the intestinal (third) phase of gastric secretion., Stimulant for Secretion, Stimulants for secretion of gastrin are:, i. Presence of food in the stomach., ii. Stimulation of local nervous plexus in stomach, and small intestine., iii. Vagovagal reflex during the gastric phase of, gastric secretion: Gastrin-releasing polypeptide, is released at the vagal nerve ending. It causes, the secretion of gastrin by stimulating the G cells, or TG cells., , TABLE 44.1: Gastrointestinal hormones, Hormone, , Source of secretion, , Actions, , G cells in stomach, TG cells in GI tract, Islets in fetal pancreas, Anterior pituitary, Brain, , Stimulates gastric secretion and motility, Promotes growth of gastric mucosa, Stimulates release of pancreatic hormones, Stimulates secretion of pancreatic juice, Stimulates secretion of pancreatic hormones, , S cells of small intestine, , Stimulates secretion of watery and alkaline pancreatic, secretion, Inhibits gastric secretion and motility, Constricts pyloric sphincter, Increases potency of cholecystokinin action, , Cholecystokinin, , I cells of small intestine, , Contracts gallbladder, Stimulates pancreatic secretion with enzymes, Accelerates secretin activity, Increases enterokinase secretion, Inhibits gastric motility, Increases intestinal motility, Augments contraction of pyloric sphincter, Suppresses hunger, Induces drug tolerance to opioids, , Gastric inhibitory peptide, (GIP), , K cells in duodenum and jejunum, Antrum of stomach, , Stimulates insulin secretion, Inhibits gastric secretion and motility, , Vasoactive intestinal, polypeptide (VIP), , Stomach, Small and large intestines, , Dilates splanchnic (peripheral) blood vessels, Inhibits Hcl secretion in gastric juice, Stimulates secretion of succus entericus, Relaxes smooth muscles of intestine, Augments acetylcholine action on salivary glands, Stimulates insulin secretion, , Glucagon, , α-cells in pancreas, A cells in stomach, L cells in intestine, , Increases blood sugar level, , Glicentin, , L cells in duodenum and jejunum, , Increases blood sugar level, , Glucagon-like polypeptide-1, (GLP-1), , α-cells in pancreas, Brain, , Stimulates insulin secretion, Inhibits gastric motility, , GLP-2, , L cells in ileum and colon, , Suppresses appetite, , Gastrin, , Secretin, , Contd...
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Chapter 44 t Gastrointestinal Hormones 283, Contd..., Hormone, , Source of secretion, , Actions, , Somatostatin, , Hypothalamus, D cells in pancreas, D cells in stomach and small, intestine, , Inhibits secretion of growth hormone, Inhibits gastric secretion and motility, Inhibits secretion of pancreatic juice, Inhibits secretion of GI hormones, , Pancreatic polypeptide, , PP cells in pancreas, Small intestine, , Increases secretion of glucagons, Decreases pancreatic secretion, , Peptide YY, , L cells of ileum and colon, , Inhibits gastric secretion and motility, Reduces secretion of pancreatic juice, Inhibits intestinal motility and bowel passage, Suppresses appetite and food intake, , Neuropeptide Y, , Ileum and colon, Brain and autonomic nervous system Increases blood flow in enteric blood vessels, (ANS), , Motilin, , Mo cells in stomach and intestine, Enterochromoffin cells in intestine, , Accelerates gastric emptying, Increases movements of small intestine, Increases peristalsis in colon, , Substance P, , Brain, Small intestine, , Increases movements of small intestine, , Ghrelin, , Stomach, Hypothalamus, Pituitary, Kidney, Placenta, , Promotes growth hormone (GH) release, Induces appetite and food intake, Stimulates gastric emptying, , Actions, Gastrin:, i. Stimulates gastric glands to secrete gastric juice, with more pepsin and hydrochloric acid., ii. Accelerates gastric motility., iii. Promotes growth of gastric mucosa., iv. Stimulates secretion of pancreatic juice, which, is rich in enzymes., v. Stimulates islets of Langerhans in pancreas to, release pancreatic hormones., 2. SECRETIN, Secretin is a peptide hormone with 27 amino acid, residues. Historical importance of secretin is that, it was, the first ever hormone discovered. It was discovered, in 1902 by Bayliss and Starling. It is secreted by the S, cells of duodenum, jejunum and ileum., Secretin is first produced in an inactive form called, prosecretin. It is converted into secretin by the acidity, of chyme., Stimulant for Secretion, Stimulant for the release and activation of prosecretin is, the acid chyme entering the duodenum from stomach., , Products of protein digestion also stimulate secretin, secretion., Actions, Major actions, Secretin stimulates exocrine pancreatic secretion. It acts, on the cells of pancreatic ductule via cyclic AMP and, causes secretion of large amount of watery juice with, high content of bicarbonate ion. Bicarbonate content of, pancreatic juice (released by secretin) has functional, significance (Chapter 39)., Other actions, Secretin:, i. Inhibits secretion of gastric juice, ii. Inhibits motility of stomach, iii. Causes constriction of pyloric sphincter, iv. Increases the potency of action of cholecystokinin, on pancreatic secretion., 3. CHOLECYSTOKININ, Cholecystokinin is made up of 39 amino acid residues., Previously it was thought that there were two separate, hormones, namely pancreozymin and cholecystokinin. It
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284 Section 4 t Digestive System, was thought that pancreozymin stimulated the secretion, of pancreatic juice with large amount of enzymes and the, cholecystokinin stimulated the contraction of gallbladder., But now it is established that the same hormone has, actions on both pancreas and gallbladder. So, it is, named as cholecystokinin-pancreozymin (CCK-PZ) or, cholecystokinin (CCK)., Cholecystokinin is secreted by I cells in mucosa of, duodenum and jejunum. A small quantity of the hormone, is secreted in the ileum also., Stimulant for Secretion, Stimulant for the release of this hormone is the presence, of chyme-containing digestive products of fats and, proteins, viz. fatty acids, peptides and amino acids in, the upper part of small intestine., Actions, , Actions, Gastric inhibitory peptide (GIP):, i. Stimulates the beta cells in the islets of, Langerhans in pancreas to release insulin., It causes insulin secretion, whenever chyme, with glucose enters the small intestine. Hence, it is called glucose-dependent insulinotropic, hormone., ii. Inhibits the secretion of gastric juice., iii. Inhibits gastric motility., Recent studies reveal that GIP does not show, significant action on gastric secretion., 5. VASOACTIVE INTESTINAL POLYPEPTIDE, Vasoactive intestinal polypeptide (VIP) contains 28, amino acid residues. This polypeptide is secreted in the, stomach and small intestine. A small amount of this, hormone is also secreted in large intestine., , Major actions, Cholecystokinin:, i. Contracts gallbladder., ii. Stimulates exocrine pancreatic secretion: It, activates the pancreatic acinar cells via the, second messenger inositol triphosphate., Cholecystokinin causes secretion of pancreatic, juice with large amount of enzymes., Other actions, Cholecystokinin:, i. Accelerates the activity of secretin to produce, alkaline pancreatic juice, with large amount of, bicarbonate ions., ii. Increases the secretion of enterokinase., iii. Inhibits the gastric motility., iv. Increases the motility of intestine., v. Augments contraction of pyloric sphincter., vi. Plays an important role in satiety by suppressing, hunger., vii. Induces drug tolerance to opioids., 4. GLUCOSE-DEPENDENT, INSULINOTROPIC HORMONE, Earlier it was called gastric inhibitory peptide (GIP). It is, a peptide hormone, formed by 42 amino acid residues., It is secreted by K cells in duodenum and in jejunum. It, is also secreted in antrum of stomach., , Stimulant for Secretion, Presence of acid chyme in the stomach and intestine, causes secretion of VIP., Actions, Vasoactive intestinal polypeptide (VIP):, i. Dilates splanchnic (peripheral) blood vessels., ii. Inhibits hydrochloric acid secretion in gastric, juice., iii. Stimulates secretion of succus entericus with, large amounts of electrolytes and water., iv. Relaxes smooth muscles of intestine., v. Augments action of acetylcholine on salivary, glands., vi. Stimulates insulin secretion., 6. GLUCAGON, Glucagon has 29 amino acid residues. It is secreted, mainly by alpha cells of islets of Langerhans in, pancreas. It is also secreted by A cells in the stomach, and L cells in the intestine. In intestine, it is secreted as, preproglucagon., , Stimulant for Secretion, Presence of food with more fat and protein in the, stomach is the stimulant for glucagon secretion in, stomach and duodenum. Hypoglycemia is the stimulant, for secretion of pancreatic glucagon., , Stimulant for Secretion, GIP is secreted when chyme containing glucose and fat, enters the duodenum., , Action, Glucagon increases blood sugar level (Chapter 69).
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Chapter 44 t Gastrointestinal Hormones 285, 7. GLICENTIN, Glicentin polypeptide is secreted by L cells in duodenum, and jejunum and α-cells of pancreatic islets. It is also, secreted in brain., Precursor of this hormone is the preproglucagon. In, intestine, the preproglucagon is converted into glicentin, and glucagon-like polypeptide-2 (GLP-2). In pancreas, it, is converted into glucagon, glucagon-like polypeptide-1, (GLP-1) and major proglucagon fragment., Stimulant for Secretion, Glicentin is secreted when chyme with fat and protein, enters the intestine., Action, Like glucagon, glicentin also increases the blood sugar, level., 8. GLUCAGON-LIKE POLYPEPTIDE-1, , and D cells of pancreatic islets also. Somatostatin is, secreted in two forms, one with 14 amino acids and the, other one with 28 amino acids., Stimulant for Secretion, Presence of chyme with glucose and proteins in stomach, and small intestine causes release of somatostatin., Actions, Somatostatin:, i. Inhibits the secretion of growth hormone (GH), and thyroid-stimulating hormone (TSH) from, anterior pituitary, ii. Inhibits gastric secretion and motility, iii. Inhibits secretion of pancreatic juice, iv. Inhibits secretion of GI hormones such as:, a. Gastrin, b. Cholecystokinin (CCK), c. Vasoactive intestinal polypeptide (VIP), d. Gastric inhibitory peptide (GIP)., , Glucagon-like polypeptide-1 (GLP-1) is secreted in, α-cells of pancreatic islets (see above). Structurally, it is, similar to GLP-2 and glucagon. It is found in brain also., , 11. PANCREATIC POLYPEPTIDE, , Stimulant for Secretion, , Source of Secretion, , Presence of food with glucose in the small intestine, stimulates the release of GLP-1., , Pancreatic polypeptide is a polypeptide with 36 amino, acid residues. It is secreted mainly by the PP cells of, the islets of Langerhans in pancreas. It is also found in, small intestine (Table 44.1)., , Actions, Glucagon-like polypeptide-1 (GLP-1):, i. Stimulates the insulin secretion from β-cells of, islets in pancreas, ii. Inhibits gastric motility., , Stimulant for Secretion, Pancreatic polypeptide is secreted by the presence of, chyme with proteins in the small intestine. It is also, secreted in conditions like hypoglycemia, fasting and, , 9. GLUCAGON-LIKE POLYPEPTIDE-2, , exercise., , Glucagon-like polypeptide-2 (GLP-2) is secreted by L, cells in ileum and colon (see above). Structurally, it is, , Actions, , similar to GLP-1 and glucagons. Like GLP-1, it is also, found in brain., Stimulant for Secretion, Presence of food with glucose in the small intestine, stimulates the release of GLP-2 also., Action, GLP-2 is believed to suppress appetite., , Pancreatic polypeptide:, i. Increases the secretion of glucagon from α-cells, of islets of Langerhans in pancreas., ii. Decreases the secretion of pancreatic juice from, exocrine part of pancreas., 12. PEPTIDE YY, Polypeptide YY with 36 amino acid residues, is structurally related to pancreatic polypeptide and neuropeptide Y. It is secreted in L cells of ileum and colon., , 10. SOMATOSTATIN, Somatostatin was first found in hypothalamus and named, as growth hormone-inhibiting hormone. Now it is found, in D cells of stomach and upper part of small intestine, , Stimulant for Secretion, Presence of fat-containing chyme stimulates the release, of peptide YY.
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286 Section 4 t Digestive System, Actions, , Stimulant for Secretion, , Peptide YY:, , Secretion of substance P in intestine is caused by the, presence of chyme., , i. Inhibits gastric secretion and motility, ii. Reduces secretion of pancreatic juice, iii. Inhibits the intestinal motility and stops passage, of bowel beyond ileum (ileal brake), iv. Suppresses appetite and food intake., 13. NEUROPEPTIDE Y, , Actions, In GI tract, substance P increases the mixing and, propulsive movements of small intestine (refer Chapter, 141 for its actions in brain)., 16. GHRELIN, , Neuropeptide Y contains 36 amino acid residues. It is, structurally related to pancreatic polypeptide and peptide, YY. It is secreted by enteric nerve endings particularly in, ileum and colon. It is also secreted in medulla, hypothalamus and neurons of autonomic nervous system, (ANS)., , Ghrelin is a recently discovered hormone. This 28, amino acid polypeptide is synthesized by epithelial, cells in the fundus of stomach. It is also produced in, smaller amounts in hypothalamus, pituitary, kidney and, placenta., , Stimulant for Secretion, , Stimulant for Secretion, , Secretion of neuropeptide Y is stimulated by fatcontaining chyme., , Secretion of ghrelin increases during fasting and, decreases when stomach is full., , Action, , Actions, , Neuropeptide Y increases the blood flow in enteric blood, vessels and stimulates food intake (Chapter 141)., , Ghrelin:, , 14. MOTILIN, Motilin is built by 22 amino acid residues. It is secreted, by Mo cells, which are present in stomach and intestine., It is also believed to be secreted by enterochromoffin, cells of intestine., Stimulant for Secretion, Motilin is secreted when the chyme from stomach enters, the duodenum., , i. Promotes the secretion of growth hormone (GH), by stimulating somatotropes (growth hormone, synthesizing cells) in anterior pituitary. Receptors, for this hormone called growth hormone, secretogogues receptor (GHS-R) were identified, in the somatotropes before the discovery of the, hormone itself. These receptors are also found, in adipose tissue, heart and hypothalamus., ii. Induces appetite and food intake by acting via, feeding center in hypothalamus (Chapter 149)., iii. Stimulates gastric emptying., , Actions, , OTHER GASTROINTESTINAL HORMONES, , Motilin:, , Mucosa of GI tract secretes many other hormones such, as:, 1. Enkephalins, 2. Dynorphin, 3. Neurotensin, 4. Serotonin, 5. Urogastrone, 6. Enterocrinin, 7. Villikinin, 8. Guanylin, 9. Bombesin., However, the significant biological actions of these, hormones on GI tract are not clear., , i. Accelerates gastric emptying, ii. Increases the mixing and propulsive movements, of small intestine, iii. Increases the peristalsis in colon., 15. SUBSTANCE P, Source of Secretion, Substance P is a neurotransmitter with 11 amino acid, residues. It is secreted at the pain nerve endings in, brain and enteric nerve endings in small intestine.
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Digestion, Absorption, and Metabolism, of Carbohydrates, , , , , , , Chapter, , 45, , CARBOHYDRATES IN DIET, DIGESTION, ABSORPTION, METABOLISM, DIETARY FIBER, , CARBOHYDRATES IN DIET, , DIGESTION OF CARBOHYDRATES, , Human diet contains three types of carbohydrates:, , IN THE MOUTH, , 1. POLYSACCHARIDES, , Enzymes involved in the digestion of carbohydrates, are known as amylolytic enzymes. The only amylolytic, enzyme present in saliva is the salivary amylase or, ptyalin (Chapter 37)., , Large polysaccharides are glycogen, amylose and, amylopectin, which are in the form of starch (glucose, polymers). Glycogen is available in non-vegetarian diet., Amylose and amylopectin are available in vegetarian, diet because of their plant origin., 2. DISACCHARIDES, Two types of disaccharides are available in the diet., i. Sucrose (Glucose + Fructose), which is called, table sugar or cane sugar, ii. Lactose (Glucose + Galactose), which is the, sugar available in milk., 3. MONOSACCHARIDES, Monosaccharides consumed in human diet are mostly, glucose and fructose., Other carbohydrates in the diet include, i. Alcohol, ii. Lactic acid, iii. Pyruvic acid, iv. Pectins, v. Dextrins, vi. Carbohydrates in meat., Diet also contains large amount of cellulose, which, cannot be digested in the human GI tract so it is not, considered as a food for human beings., , IN THE STOMACH, Gastric juice contains a weak amylase, which plays a, minor role in digestion of carbohydrates., IN THE INTESTINE, Amylolytic enzymes present in the small intestine are, derived from pancreatic juice and succus entericus, (Table 45.1)., Amylolytic Enzyme in Pancreatic Juice, Pancreatic juice contains pancreatic amylase (Chapter, 39)., Amylolytic Enzymes in Succus Entericus, Amylolytic enzymes present in succus entericus are, maltase, sucrase, lactase, dextrinase and trehalase, , (Chapter 41)., FINAL PRODUCTS OF, CARBOHYDRATE DIGESTION, Final products of carbohydrate digestion are monosac, charides, which are glucose, fructose and galactose.
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288 Section 4 t Digestive System, TABLE 45.1: Digestion of carbohydrates, Area, , Juice, , Enzyme, , Substrate, , End product, , Mouth, , Saliva, , Salivary amylase, , Polysaccharides – cooked, starch, , Disaccharides – dextrin and, maltose, , Stomach, , Gastric juice, , Gastric amylase, , Weak amylase, , The action is negligible, , Pancreatic juice, , Pancreatic amylase, , Polysaccharides, , Disaccharides, – Dextrin, maltose and maltriose, , Sucrase, , Sucrose, , Glucose and fructose, , Maltase, , Maltose and maltriose, , Glucose, , Lactase, , Lactose, , Glucose and galactose, , Dextrinase, , Dextrin, maltose and maltriose Glucose, , Trehalase, , Trehalose, , Small, intestine, , Succus entericus, , Glucose represents 80% of the final product of carbo, hydrate digestion. Galactose and fructose represent the, remaining 20%., , ABSORPTION OF CARBOHYDRATES, Carbohydrates are absorbed from the small intestine, mainly as monosaccharides, viz. glucose, galactose, and fructose., ABSORPTION OF GLUCOSE, Glucose is transported from the lumen of small intestine, into the epithelial cells in the mucus membrane of small, intestine, by means of sodium cotransport. Energy for, this is obtained by the binding process of sodium ion, and glucose molecule to carrier protein., From the epithelial cell, glucose is absorbed into the, portal vein by facilitated diffusion. However, sodium ion, moves laterally into the intercellular space. From here, it, is transported into blood by active transport, utilizing the, energy liberated by breakdown of ATP., ABSORPTION OF GALACTOSE, Galactose is also absorbed from the small intestine in, the same mechanism as that of glucose., ABSORPTION OF FRUCTOSE, Fructose is absorbed into blood by means of facilitated, diffusion. Some molecules of fructose are converted, into glucose. Glucose is absorbed as described above., , METABOLISM OF CARBOHYDRATES, Metabolism is the process in which food substances, undergo chemical and energy transformation. After, , Glucose, , digestion and absorption, food substances must be, utilized by the body. The utilization occurs mainly by, oxidative process in which the carbohydrates, proteins, and lipids are burnt slowly to release energy. This, process is known as catabolism., Part of the released energy is utilized by tissues for, physiological actions and rest of the energy is stored as, rich energy phosphate bonds and in the form of proteins,, carbohydrates and lipids in the tissues. This process is, called anabolism., Metabolism of carbohydrates is given in the form of, schematic diagram (Fig. 45.1)., , DIETARY FIBER, Dietary fiber or roughage is a group of food particles, which pass through stomach and small intestine, without, being digested and reach the large intestine unchanged., Other nutritive substances of food are digested and, absorbed before reaching large intestine., Characteristic feature of dietary fiber is that it is, not digestible by digestive enzymes. So it escapes, digestion in small intestine and passes to large intestine., It provides substrate for microflora of large intestine and, increases the bacterial mass. The anaerobic bacteria, in turn, degrade the fermentable components of the, fiber. Thus, in large intestine, some of the components, of fiber are broken down and absorbed and remaining, components are excreted through feces., Components of Dietary Fiber, Major components of dietary fiber are cellulose,, hemicelluloses, Dglucans, pectin, lignin and gums., Cellulose, hemicelluloses and pectin are partially, degradable, while other components are indigestible., Dietary fiber also contains minerals, antioxidants and, other chemicals that are useful for health.
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Chapter 45 t Digestion, Absorption and Metabolism of Carbohydrates 289, , FIGURE 45.1: Schematic diagram of carbohydrate metabolism, , Source of Dietary Fiber, Source of dietary fiber are fruits, vegetables, cereals,, bread and wheat grain (particularly its outer layer)., Health Benefits of Dietary Fiber, 1. By intake of high dietary fiber food, some disease, producing food substances may be decreased in, quantity or completely excluded in diet, 2. Dietary fiber helps in weight maintenance because it, requires more chewing and promotes hunger satisfaction by delaying the emptying of stomach and by, giving the person a sense of fullness of stomach, , 3. Diet with high fiber content tends to be low in energy, and it is also useful in reducing the body weight, 4. Dietary fiber increases the formation of bulk and, soft feces and eases defecation, 5. It contains some useful substances such as, antioxidants, 6. Some components of dietary fiber also reduce blood, cholesterol level and thereby, decrease the risk of, some diseases such as coronary heart disease and, gallstones, , 7. Dietary fiber is also suggested to prevent or to, treat some disorders such as constipation, bowel, syndrome, diabetics, ulcer and cancer.
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Digestion, Absorption, and Metabolism, of Proteins, , , , , , Chapter, , 46, , PROTEINS IN DIET, DIGESTION, ABSORPTION, METABOLISM, , PROTEINS IN DIET, Foodstuffs containing high protein content are meat,, fish, egg and milk. Proteins are also available in wheat,, soybeans, oats and various types of pulses., Proteins present in common foodstuffs are:, 1. Wheat: Glutenin and gliadin, which constitute, gluten, 2. Milk: Casein, lactalbumin, albumin and myosin, 3. Egg: Albumin and vitellin, 4. Meat: Collagen, albumin and myosin., , Dietary proteins are formed by long chains of amino, acids, bound together by peptide linkages., , DIGESTION OF PROTEINS, Enzymes responsible for the digestion of proteins are, called proteolytic enzymes., IN THE MOUTH, Digestion of proteins does not occur in mouth, since, saliva does not contain any proteolytic enzymes. So, the, digestion of proteins starts only in stomach (Table 46.1)., , TABLE 46.1: Digestion of proteins, Area, , Juice, , Enzyme, , Substrate, , End product, , Mouth, , Saliva, , No proteolytic enzyme, , Polysaccharides –, cooked starch, , Disaccharides – dextrin and, maltose, , Stomach, , Gastric juice, , Pepsin, , Proteins, , Proteoses, peptones, large, polypeptides, , Proteoses, Peptones, , Dipeptides, Tripeptides, Polypeptides, , Carboxypeptidases A and B, , Dipeptides, Tripeptides, Polypeptides, , Amino acids, , Dipeptidases, , Dipeptides, , Tripeptidases, , Tripeptides, , Amino peptidases, , Large polypeptides, , Trypsin, Pancreatic juice, Small, intestine, Succus entericus, , Chymotrypsin, , Amino acids
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Chapter 46 t Digestion, Absorption and Metabolism of Proteins 291, , FIGURE 46.1: Schematic diagram of protein metabolism, , IN THE STOMACH, Pepsin is the only proteolytic enzyme in gastric juice, (Chapter 38). Rennin is also present in gastric juice. But, , it is absent in human., , dipeptidases, tripeptidases and aminopeptidases, , (Chapter 41)., , FINAL PRODUCTS OF PROTEIN DIGESTION, , IN THE SMALL INTESTINE, , Final products of protein digestion are the amino acids,, which are absorbed into blood from intestine., , Most of the proteins are digested in the duodenum and, jejunum by the proteolytic enzymes of the pancreatic, juice and succus entericus., , ABSORPTION OF PROTEINS, , Proteolytic Enzymes in Pancreatic Juice, Pancreatic juice contains trypsin, chymotrypsin and, carboxypeptidases. Trypsin and chymotrypsin are, called endopeptidases, as these two enzymes break the, , Proteins are absorbed in the form of amino acids from, small intestine. The levo amino acids are actively, absorbed by means of sodium cotransport, whereas,, the dextro amino acids are absorbed by means of, facilitated diffusion., , interior bonds of the protein molecules (Chapter 39)., , Absorption of amino acids is faster in duodenum, and jejunum and slower in ileum., , Proteolytic Enzymes in Succus Entericus, , METABOLISM OF PROTEINS, , Final digestion of proteins is by the proteolytic, enzymes present in the succus entericus. It contains, , Metabolism of proteins is given in the form of a schematic, diagram (Fig. 46.1).
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Digestion, Absorption, and Metabolism, of Lipids, , , , , , , , , , Chapter, , 47, , LIPIDS IN DIET, DIGESTION, ABSORPTION, STORAGE, TRANSPORT IN BLOOD – LIPOPROTEINS, ADIPOSE TISSUE, METABOLISM, LIPID PROFILE, , LIPIDS IN DIET, , 1. Monounsaturated Fats, , Lipids are mostly consumed in the form of neutral fats,, which are also known as triglycerides. Triglycerides, are made up of glycerol nucleus and free fatty acids., Triglycerides form the major constituent in foods of, animal origin and much less in foods of plant origin., Apart from triglycerides, usual diet also contains small, quantities of cholesterol and cholesterol esters., Dietary fats are classified into two types:, 1. Saturated fats, 2. Unsaturated fats., , Unsaturated fats which contain one double bond bet, ween the carbon atoms are called monounsaturated, fats., , SATURATED FATS, Saturated fats are the fats which contain triglycerides, formed from only saturated fatty acids. The fatty acids, having maximum amount of hydrogen ions without, any double bonds between carbon atoms are called, saturated fatty acids., UNSATURATED FATS, Fats containing unsaturated fatty acids are known as, unsaturated fats. Unsaturated fatty acids are fatty acids, formed by dehydrogenation of saturated fatty acids., Unsaturated fats are classified into three types:, 1. Monounsaturated fats, 2. Polyunsaturated fats, 3. Trans fats., , 2. Polyunsaturated Fats, Unsaturated fats with more than one double bond, between the carbon atoms are called polyunsaturated, fats. Polyunsaturated fats belong to the family of, essential fatty acids (fatty acids required in diet)., Polyunsaturated fats are of two types:, 1. Omega-3 fats or omega3 fatty acids having double, bond in the third space from the end of the carbon, chain, 2. Omega-6 fats or omega6 fatty acids having double, bond in the sixth space from the end of the carbon, chain., Both omega-3 and omega-6 fatty acids are beneficial, to the body. However, consuming too much of omega6, fatty acids results in hazards than benefits. So, the diet, containing 3 : 1 ratio of omega-6 to omega-3 fatty acids, is often recommended by experts., 3. Trans Fats, Trans fats or trans fatty acids are unsaturated fatty acids,, with molecules containing trans (across or opposite, side) double bonds between carbon atoms.
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Chapter 47 t Digestion, Absorption and Metabolism of Lipids 293, Sources and the functions of the different types of, dietary fats are listed in Table 47.1., , Lipolytic Enzymes in Pancreatic Juice, Pancreatic lipase is the most important enzyme for the, , Lipids are digested by lipolytic enzymes., , digestion of fats. Other lipolytic enzymes of pancreatic, juice are cholesterol ester hydrolase, phospholipase A, and phospholipase B (Chapter 39)., , IN THE MOUTH, , Lipolytic Enzyme in Succus Entericus, , Saliva contains lingual lipase. This enzyme is secreted, by lingual glands of mouth and swallowed along with, saliva. So, the lipid digestion does not commence in the, mouth (Table 47.2) (Chapter 37)., , Intestinal lipase is the only lipolytic enzyme present in, , IN THE STOMACH, , Fatty acids, cholesterol and monoglycerides are the, final products of lipid digestion., , DIGESTION OF LIPIDS, , Gastric lipase or tributyrase is the lipolytic enzyme, present in gastric juice (Chapter 38)., , IN THE INTESTINE, Almost all the lipids are digested in the small intestine, because of the availability of bile salts, pancreatic, lipolytic enzymes and intestinal lipase., Role of Bile Salts, Bile salts play an important role in the digestion of lipids, (Chapter 40)., , succus entericus (Chapter 41)., FINAL PRODUCTS OF FAT DIGESTION, , ABSORPTION OF LIPIDS, Monoglycerides, cholesterol and fatty acids from the, micelles enter the cells of intestinal mucosa by simple, diffusion., From here, further transport occurs as follows:, 1. In the mucosal cells, most of the monoglycerides, are converted into triglycerides. Triglycerides are, also formed by re-esterification of fatty acids with, more than 10 to 12 carbon atoms. Some of the, cholesterol is also esterified., , TABLE 47.1: Sources and functions of dietary fats, Type of fat, , Saturated fats, , Monounsaturated fats, , Polyunsaturated fats, , Trans fats, , Sources, , Functions, , Full fat milk, cheese, cream, butter. Commercially, baked biscuits and pastries, Increase blood cholesterol and thereby increase, Deepfried fast food, the risk of atherosclerosis and coronary heart, Coconut oil and palm oil, diseases, Fatty meat, Oils (canola, olive and peanut oils), Decrease blood cholesterol and thereby, Nuts (cashews, almonds, hazelnuts and peanuts), decrease the risk of coronary heart diseases, Margarine, Fruits and vegetables, Vegetable oils (sunflower, safflower, corn or soy, oils), Nuts (walnuts), Flax seeds, Polyunsaturated margarines, Lean meat, Fish and sea foods, Egg, Milk, Cheese and table margarines, Lamb and beef, , Decrease, Blood cholesterol and triglycerides and thereby, reduces blood pressure, Risk of coronary heart diseases, Risk of obesity, Platelet aggregation and prevents excess blood, clotting, Inflammation throughout body, Increase, Diseasecountering actions in the body, Increase low density lipoproteins and thereby, increase the risk of atherosclerosis and, coronary heart diseases
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294 Section 4 t Digestive System, TABLE 47.2: Digestion of lipids, Area, , Juice, , Enzyme, , Substrate, , Fatty acid, 1, 2diacylglycerol, , Mouth, , Saliva, , Lingual lipase, , Stomach, , Gastric juice, , Gastric lipase (weak lipase) Triglycerides, , Fatty acids, Glycerol, , Pancreatic lipase, , Triglycerides, , Monoglycerides, Fatty acid, , Cholesterol ester hydrolase, , Cholesterol ester, , Free cholesterol, Fatty acid, , Phospholipase A, , Phospholipids, , Lysophospholipids, , Phospholipase B, , Lysophospholipids, , Phosphoryl choline, Free fatty acids, , Colipase, , Facilitates action of, pancreatic lipase, , –, , Phospholipids, , Lysophospholipids, , Cholesterol esters, , Cholesterol and fatty acids, , Triglycerides, , Fatty acids, Glycerol (weak action), , Pancreatic juice, Small, intestine, , Bilesaltactivated lipase, Succus entericus, , Intestinal lipase, , Triglycerides, , End product, , Triglycerides and cholesterol esters are coated with, a layer of protein, cholesterol and phospholipids to form, the particles called chylomicrons., Chylomicrons cannot pass through the membrane, of the blood capillaries because of the larger size. So,, these lipid particles enter the lymph vessels and then, are transferred into blood from lymph., 2. Fatty acids containing less than 10 to 12 carbon, atoms enter the portal blood from mucosal cells and, are transported as free fatty acids or unesterified, fatty acids. Most of the fats are absorbed in the, upper part of small intestine. Presence of bile is, essential for fat absorption., , When other tissues of the body need energy,, triglycerides stored in adipose tissue is hydrolyzed into, FFA and glycerol. FFA is transported to the body tissues, through blood., , STORAGE OF LIPIDS, , Lipoproteins are the small particles in the blood which, contain cholesterol, phospholipids, triglycerides and, proteins. Proteins are betaglobulins called apoproteins., , Lipids are stored in adipose tissue and liver. Fat stored, in adipose tissue is called neutral fat or tissue fat., When chylomicrons are traveling through capillaries of, adipose tissue or liver, the enzyme called lipoprotein, lipase present in the capillary endothelium hydrolyzes, triglycerides of chylomicrons into free fatty acids (FFA), and glycerol. FFA and glycerol enter the fat cells, (adipocytes or lipocytes) of the adipose tissue or liver, cells. Then, the FFA and glycerol are again converted, into triglycerides and stored in these cells. Other contents, of chylomicrons such as cholesterol and phospholipids,, which are released into the blood combine with proteins, to form lipoproteins., , TRANSPORT OF LIPIDS IN, BLOOD – LIPOPROTEINS, Free fatty acids are transported in the blood in, combination with albumin. Other lipids are transported, in the blood, in the form of lipoproteins., LIPOPROTEINS, , Classification of Lipoproteins, Lipoproteins are classified into four types on the basis, of their density:, 1. Very-low-density lipoproteins (VLDL): Contain high, concentration of triglycerides (formed from FFA and, glycerol) and moderate concentration of cholesterol, and phospholipids, 2. Intermediate-density lipoproteins (IDL): Formed, by the removal of large portion of triglycerides, from VLDL by lipoprotein lipase. Concentration of
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Chapter 47 t Digestion, Absorption and Metabolism of Lipids 295, cholesterol and phospholipids increases because of, removal of triglycerides, 3. Low-density lipoproteins (LDL): Formed from IDL by, the complete removal of triglycerides. These lipo, proteins contain only cholesterol and phospholipids, 4. High-density lipoproteins (HDL): Contain high, concentrations of proteins with low concentration of, cholesterol and phospholipids., All the lipoproteins are synthesized in liver. HDL is, synthesized in intestine also., , Very-low-density lipoprotein, Verylowdensity lipoprotein (VLDL) carries cholesterol, from liver to organs and tissues in the body. It is also, associated with atherosclerosis and heart disease., , ADIPOSE TISSUE, , Primary function of lipoproteins is to transport the lipids, via blood to and from the tissues. Functions of each type, of lipoproteins are given in Table 47.3., , Adipose tissue or fat is a loose connective tissue that, forms the storage site of fat in the form of triglycerides., It is composed of adipocytes, which are also called, fat cells or lipocytes. Obesity does not depend on the, body weight, but on the amount of body fat, specifically, adipose tissue., Adipose tissue is of two types, white adipose tissue, and brown adipose tissue., , Importance of Lipoproteins, , WHITE ADIPOSE TISSUE OR WHITE FAT, , High-density lipoprotein, , White adipose tissue is distributed through the body, beneath the skin, forming subcutaneous fat. It also, surrounds the internal organs. This adipose tissue is, formed by fat cells which are unilocular, i.e. these cells, contain one large vacuole filled with fat., , Functions of Lipoproteins, , Highdenisty lipoprotein (HDL) is referred as the, ‘good cholesterol’ because it carries cholesterol and, phospholipids from tissues and organs back to the, liver for degradation and elimination. It prevents the, deposition of cholesterol on the walls of arteries, by, carrying cholesterol away from arteries to the liver., High level of HDL is a good indicator of a healthy, heart, because it reduces the blood cholesterol level., HDL also helps in the normal functioning of some, hormones and certain tissues of the body. It is also used, for the formation of bile in liver., Low-density lipoprotein, Lowdensity lipoprotein (LDL) is considered as the, ‘bad cholesterol’ because it carries cholesterol and, phospholipids from the liver to different areas of the, body, viz. muscles, other tissues and organs such as, heart. It is responsible for deposition of cholesterol on, walls of arteries causing atherosclerosis (blockage and, hardening of the arteries). High level of LDL increases, the risk of heart disease., TABLE 47.3: Functions of lipoproteins, Lipoproteins, , Functions, , VLDL, , Transports triglycerides from liver to, adipose tissue, , IDL, , Transports triglycerides, cholesterol and, phospholipids from liver to peripheral, tissues, , LDL, , Transports cholesterol and phospholipids, from liver to tissues and organs like, heart, , HDL, , Transports cholesterol and phospholipids, from tissues and organs like heart back, to liver, , Functions of White Adipose Tissue, White adipose tissue has three functions:, 1. Storage of energy: Main function of white adipose, tissue is the storage of lipids. Utilization or storage, of fat is regulated by hormones, particularly insulin,, depending upon the blood glucose level. If the, blood glucose level increases, insulin stimulates, synthesis and storage of fat in white adipose tissue, (Chapter 69). On the other hand, if blood glucose, level decreases insulin causes release of fat from, adipose tissue. Released fat is utilized for energy, 2. Heat insulation: Insulation function is due to, the presence of adipose tissue beneath the skin, (subcutaneous adipose tissue), 3. Protection of internal organs: White adipose tissue, protects the body and internal organs by surrounding, them and by acting like a mechanical cushion., BROWN ADIPOSE TISSUE OR BROWN FAT, Brown adipose tissue is a specialized form of adipose, tissue, having the function opposite to that of white, adipose tissue. It is present only in certain areas of the, body such as back of neck and intrascapular region., It is abundant in infants forming about 5% of total, adipose tissue. After infancy, brown adipose tissue, disappears gradually and forms only about 1% of total, adipose tissue in adults. It is formed by fat cells which, are multilocular, i.e. these cells contain many small
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296 Section 4 t Digestive System, , FIGURE 47.1: Schematic diagram of lipid metabolism, , vacuoles filled with fat. The coloration of this adipose, tissue is due to high vascularization and large number, of iron-rich mitochondria., Functions of Brown Adipose Tissue, Brown adipose tissue does not store lipids but, generates heat by burning lipids. In infants and, hibernating animals, brown adipose tissue plays an, important role in regulating body temperature via, , non-shivering thermogenesis. Heat production in, , brown fat is very essential for survival of infants and, small animals in cold environment. It is because,, the lipid in this tissue releases energy directly as heat., The mitochondria found in brown adipose tissue, contain a unique uncoupling protein called mitochondrial, uncoupling protein 1 (UCP1). Also called thermogenin,, this protein allows the controlled entry of protons without, adenosine triphosphate (ATP) synthesis, in order to, generate heat.
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Chapter 47 t Digestion, Absorption and Metabolism of Lipids 297, TABLE 47.4: Values of lipid profile, Lipids, , Desirable optimal level, , Borderline range, , High-risk level, , Total cholesterol, , < 200 mg/dL, , 200 to 240 mg/dL, , > 240, , mg/dL, , Triglycerides, , < 150 mg/dL, , 150 to 200 mg/dL, , > 200, , mg/dL, , mg/dL, , < 40, , mg/dL, , 60 to 100 mg/dL, , > 100, , mg/dL, , HDL, , > 60 mg/dL, , LDL, , < 60 mg/dL, , Total cholesterol – HDL ratio, , <, , 2, , METABOLISM OF LIPIDS, Metabolism of lipids is given in the form of schematic, diagram (Fig. 47.1)., LIPID PROFILE, Lipid profile is a group of blood tests which are carried, out to determine the risk of coronary artery diseases, (CAD). Results of lipid profile are considered as good, indicators of whether someone is prone to develop, stroke or heart attack, caused by atherosclerosis. In, order to plan the course of treatment, the results of the, , 40 to 60, 2 to 6, , >, , 6, , lipid profile are correlated with age, sex and other risk, factors of heart disease., Tests included in lipid profile are total cholesterol,, triglyceride, HDL, LDL, VLDL and total cholesterol –, HDL ratio., Total cholesterol to HDL ratio is helpful in predicting, atherosclerosis and CAD. It is obtained by dividing total, cholesterol by HDL. High total cholesterol and low HDL, increases the ratio. The increase in the ratio is undesirable., Conversely, high HDL and low total cholesterol lowers, the ratio and the decrease in the ratio is desirable. The, values of lipid profile are given in Table 47.4.
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298 Questions in Digestive System, , QUESTIONS IN DIGESTIVE SYSTEM, , LONG QUESTIONS, 1. What are the different types of salivary glands?, Describe the composition, functions and regulation, of secretion of saliva., 2. Explain the composition and functions of gastric, juice and give an account of hormonal regulation, of gastric secretion., 3. Describe the different phases of gastric secretion, with experimental evidences., 4. Explain the composition, functions and regulation, of secretion of pancreatic juice., 5. Describe the composition, functions and regulation, of secretion of bile. Enumerate the differences, between the liver bile and gallbladder bile. Add a, note on enterohepatic circulation., 6. Give an account of succus entericus., 7. Write an essay on gastric motility. What are the, factors influencing gastric emptying?, 8. Describe in detail, the gastrointestinal movements., , SHORT QUESTIONS, 1., 2., 3., 4., 5., 6., 7., 8., 9., 10., 11., 12., 13., 14., 15., 16., , Properties and composition of saliva., Functions of saliva., Nerve supply to salivary glands., Glands of stomach., Functions of stomach., Properties and composition of gastric juice., Functions of gastric juice, Mechanism of secretion of hydrochloric acid in, stomach., Pavlov’s pouch., Sham feeding., Cephalic phase of gastric secretion., Gastrin., Hormones acting on stomach., FTM., Peptic ulcer., Exocrine function of pancreas., , 17., 18., 19., 20., 21., 22., 23., 24., 25., 26., 27., 28., 29., 30., 31., 32., 33., 34., 35., 36., 37., 38., 39., 40., 41., 42., 43., 44., 45., 46., 47., 48., 49., 50., 51., 52., 53., 54., 55., 56., , Properties and composition of pancreatic juice., Functions of pancreatic juice., Regulation of exocrine function of pancreas., Steatorrhea., Secretin., Cholecystokinin., Composition of bile., Functions of bile., Bile salts., Bile pigments., Enterohepatic circulation., Functions of liver., Differences between liver bile and gallbladder bile., Functions of gallbladder., Jaundice., Hepatitis., Gallstones., Succus entericus., Functions of small intestine., Functions of large intestine., Mastication., Swallowing., Dysphagia., Movements of stomach., Filling and emptying of stomach., Hunger contractions., Vomiting., Movements of small intestine., Peristalsis., Movements of large intestine., Defecation., Constipation., Diarrhea., Gastrointestinal hormones., Digestion and absorption of carbohydrates., Dietary fiber., Digestion and absorption of proteins., Digestion and absorption of lipids., Lipoproteins., Brown fat.
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Section, , 5, , 48., 49., 50., 51., 52., 53., 54., 55., 56., 57., 58., 59., 60., 61., 62., 63., , Renal Physiology, and Skin, , Kidney ..................................................................................................... 301, Nephron .................................................................................................. 304, Juxtaglomerular Apparatus ..................................................................... 309, Renal Circulation ..................................................................................... 312, Urine Formation ...................................................................................... 315, Concentration of Urine ............................................................................ 325, Acidification of Urine and Role of Kidney in Acid-base Balance ............. 330, Renal Function Tests ............................................................................... 333, Renal Failure ........................................................................................... 337, Micturition ................................................................................................ 339, Dialysis and Artificial Kidney ................................................................... 346, Diuretics .................................................................................................. 348, Structure of Skin ...................................................................................... 351, Functions of Skin ..................................................................................... 354, Glands of Skin ......................................................................................... 356, Body Temperature ................................................................................... 359
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Chapter, , Kidney, , 48, , INTRODUCTION, FUNCTIONS OF KIDNEY, , , , , , , ROLE IN HOMEOSTASIS, HEMOPOIETIC FUNCTION, ENDOCRINE FUNCTION, REGULATION OF BLOOD PRESSURE, REGULATION OF BLOOD CALCIUM LEVEL, , FUNCTIONAL ANATOMY OF KIDNEY, , , , DIFFERENT LAYERS OF KIDNEY, TUBULAR STRUCTURES OF KIDNEY, , INTRODUCTION, Excretion is the process by which the unwanted, substances and metabolic wastes are eliminated from, the body., A large amount of waste materials and carbon dioxide are produced in the tissues during metabolic, process. In addition, residue of undigested food,, heavy metals, drugs, toxic substances and pathogenic, organisms like bacteria are also present in the body., All these substances must be removed to keep the, body in healthy condition. Various systems/organs in the, body are involved in performing the excretory function, viz., 1. Digestive system excretes food residues in the form, of feces. Some bacteria and toxic substances also, are excreted through feces, 2. Lungs remove carbon dioxide and water vapor, 3. Skin excretes water, salts and some wastes. It also, removes heat from the body, 4. Liver excretes many substances like bile pigments,, heavy metals, drugs, toxins, bacteria, etc. through, bile., Although various organs are involved in removal of, wastes from the body, their excretory capacity is limited., But renal system or urinary system has maximum, excretory capacity and so it plays a major role in, homeostasis., , Renal system includes:, A pair of kidneys, Ureters, Urinary bladder, Urethra., Kidneys produce the urine. Ureters transport the, urine to urinary bladder. Urinary bladder stores the urine, until it is voided (emptied). Urine is voided from bladder, through urethra (Fig. 48.1)., 1., 2., 3., 4., , FUNCTIONS OF KIDNEY, Kidneys perform several vital functions besides formation, of urine. By excreting urine, kidneys play the principal, role in homeostasis. Thus, the functions of kidney are:, 1. ROLE IN HOMEOSTASIS, Primary function of kidneys is homeostasis. It is, accomplished by the formation of urine. During the, formation of urine, kidneys regulate various activities in, the body, which are concerned with homeostasis such, as:, i. Excretion of Waste Products, Kidneys excrete the unwanted waste products, which, are formed during metabolic activities:
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302 Section 5 t Renal Physiology and Skin, organs, kidneys play major role in preventing acidosis., In fact, kidneys are the only organs, which are capable, of eliminating certain metabolic acids like sulfuric and, phosphoric acids., 2. HEMOPOIETIC FUNCTION, Kidneys stimulate the production of erythrocytes by, secreting erythropoietin. Erythropoietin is the important, stimulating factor for erythropoiesis (Chapter 10). Kidney, also secretes another factor called thrombopoietin,, which stimulates the production of thrombocytes, (Chapter 18)., 3. ENDOCRINE FUNCTION, Kidneys secrete many hormonal substances in addition, to erythropoietin and thrombopoietin (Chapter 72)., Hormones secreted by kidneys, FIGURE 48.1: Urinary system, , a. Urea (end product of amino acid metabolism), b. Uric acid (end product of nucleic acid metabolism), c. Creatinine (end product of metabolism in muscles), d. Bilirubin (end product of hemoglobin degradation), e. Products of metabolism of other substances., Kidneys also excrete harmful foreign chemical, substances such as toxins, drugs, heavy metals, pesticides, etc., ii. Maintenance of Water Balance, Kidneys maintain the water balance in the body by, conserving water when it is decreased and excreting, water when it is excess in the body. This is an important, process for homeostasis (Refer Chapter 4 for details)., iii. Maintenance of Electrolyte Balance, Maintenance of electrolyte balance, especially sodium, is in relation to water balance. Kidneys retain sodium if, the osmolarity of body water decreases and eliminate, sodium when osmolarity increases., iv. Maintenance of Acid–Base Balance, The pH of the blood and body fluids should be, maintained within narrow range for healthy living. It is, achieved by the function of kidneys (Chapter 54). Body, is under constant threat to develop acidosis, because, of production of lot of acids during metabolic activities., However, it is prevented by kidneys, lungs and blood, buffers, which eliminate these acids. Among these, , i., ii., iii., iv., v., , Erythropoietin, Thrombopoietin, Renin, 1,25-dihydroxycholecalciferol (calcitriol), Prostaglandins., , 4. REGULATION OF BLOOD PRESSURE, Kidneys play an important role in the long-term regulation, of arterial blood pressure (Chapter 103) by two ways:, i. By regulating the volume of extracellular fluid, ii. Through renin-angiotensin mechanism., 5. REGULATION OF BLOOD CALCIUM LEVEL, Kidneys play a role in the regulation of blood calcium, level by activating 1,25-dihydroxycholecalciferol into, vitamin D. Vitamin D is necessary for the absorption of, calcium from intestine (Chapter 68)., , FUNCTIONAL ANATOMY OF KIDNEY, Kidney is a compound tubular gland covered by a, connective tissue capsule. There is a depression on, the medial border of kidney called hilum, through which, renal artery, renal veins, nerves and ureter pass., DIFFERENT LAYERS OF KIDNEY, Components of kidney are arranged in three layers (Fig., 48.2):, 1. Outer cortex, 2. Inner medulla, 3. Renal sinus.
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Chapter 48 t Kidney 303, divided into 8 to 18 medullary or Malpighian pyramids., Broad base of each pyramid is in contact with cortex, and the apex projects into minor calyx., 3. Renal Sinus, Renal sinus consists of the following structures:, i. Upper expanded part of ureter called renal, pelvis, , ii. Subdivisions of pelvis: 2 or 3 major calyces and, about 8 minor calyces, iii. Branches of nerves, arteries and tributaries of, veins, iv. Loose connective tissues and fat., TUBULAR STRUCTURES OF KIDNEY, , FIGURE 48.2: Longitudinal section of kidney, , 1. Outer Cortex, Cortex is dark and granular in appearance. It contains, renal corpuscles and convoluted tubules. At intervals,, cortical tissue penetrates medulla in the form of columns,, which are called renal columns or columns of Bertini., 2. Inner Medulla, Medulla contains tubular and vascular structures, arranged in parallel radial lines. Medullary mass is, , Kidney is made up of closely arranged tubular structures, called uriniferous tubules. Blood vessels and interstitial, connective tissues are interposed between these, tubules., Uriniferous tubules include:, 1. Terminal or secretary tubules called nephrons,, which are concerned with formation of urine, 2. Collecting ducts or tubules, which are concerned, with transport of urine from nephrons to pelvis of, ureter., Collecting ducts unite to form ducts of Bellini,, which open into minor calyces through papilla. Other, details are given in Chapter 49.
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Chapter, , Nephron, , 49, , INTRODUCTION, RENAL CORPUSCLE, , , , SITUATION – TYPES OF NEPHRON, STRUCTURE, , TUBULAR PORTION OF NEPHRON, , , , , PROXIMAL CONVOLUTED TUBULE, LOOP OF HENLE, DISTAL CONVOLUTED TUBULE, , COLLECTING DUCT, PASSAGE OF URINE, , INTRODUCTION, Nephron is defined as the structural and functional unit of, kidney. Each kidney consists of 1 to 1.3 millions of nephrons., The number of nephrons starts decreasing after about 45, , to 50 years of age at the rate of 0.8% to 1% every year., Each nephron is formed by two parts (Fig. 49.1):, 1. A blind end called renal corpuscle or Malpighian, corpuscle, , 2. A tubular portion called renal tubule., , FIGURE 49.1: Structure of nephron
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Chapter 49 t Nephron 305, , RENAL CORPUSCLE, Renal corpuscle or Malpighian corpuscle is a spheroidal, and slightly flattened structure with a diameter of about, 200 µ., Function of the renal corpuscle is the filtration of, blood which forms the first phase of urine formation., SITUATION OF RENAL CORPUSCLE AND, TYPES OF NEPHRON, Renal corpuscle is situated in the cortex of the kidney, either near the periphery or near the medulla., Classification of Nephrons, Based on the situation of renal corpuscle, the nephrons, are classified into two types:, 1. Cortical nephrons or superficial nephrons: Nephrons, having the corpuscles in outer cortex of the kidney, near the periphery (Fig. 49.2). In human kidneys,, 85% nephrons are cortical nephrons., , 2. Juxtamedullary nephrons: Nephrons having, the corpuscles in inner cortex near medulla or, corticomedullary junction., Features of the two types of nephrons are given in, Table 49.1., STRUCTURE OF RENAL CORPUSCLE, Renal corpuscle is formed by two portions:, 1. Glomerulus, 2. Bowman capsule., Glomerulus, Glomerulus is a tuft of capillaries enclosed by Bowman, capsule. It consists of glomerular capillaries interposed, between afferent arteriole on one end and efferent, arteriole on the other end. Thus, the vascular system in, the glomerulus is purely arterial (Fig. 49.3)., Glomerular capillaries arise from the afferent arte, riole. After entering the Bowman capsule, the afferent, , FIGURE 49.2: Types of nephron, , FIGURE 49.3: Renal corpuscle, , TABLE 49.1: Features of two types of nephron, Features, , Cortical nephron, , Juxtamedullary nephron, , Percentage, , 85%, , 15%, , Situation of renal corpuscle, , Outer cortex near the periphery, , Inner cortex near medulla, , Short, , Long, , Loop of Henle, , Hairpin bend penetrates only up to outer, zone of medulla, , Hairpin bend penetrates up to the tip of papilla, , Blood supply to tubule, , Peritubular capillaries, , Vasa recta, , Function, , Formation of urine, , Mainly the concentration of urine and also, formation of urine
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306 Section 5 t Renal Physiology and Skin, arteriole divides into 4 or 5 large capillaries. Each large, capillary subdivides into many small capillaries. These, small capillaries are arranged in irregular loops and form, anastomosis. All the smaller capillaries finally reunite to, form the efferent arteriole, which leaves the Bowman, capsule., Diameter of the efferent arteriole is less than that, of afferent arteriole. This difference in diameter has got, functional significance., Functional histology, Glomerular capillaries are made up of single layer of, endothelial cells, which are attached to a basement, membrane. Endothelium has many pores called, fenestrae or filtration pores. Diameter of each pore is, 0.1 µ. Presence of the fenestra is the evidence of the, filtration function of the glomerulus., Bowman Capsule, Bowman capsule is a capsular structure, which enclo, ses the glomerulus., It is formed by two layers:, i. Inner visceral layer, ii. Outer parietal layer., Visceral layer covers the glomerular capillaries. It, is continued as the parietal layer at the visceral pole., Parietal layer is continued with the wall of the tubular, portion of nephron. The cleftlike space between the, visceral and parietal layers is continued as the lumen of, the tubular portion., Functional anatomy of Bowman capsule resembles, a funnel with filter paper. Diameter of Bowman capsule, is 200 µ., Functional histology, Both the layers of Bowman capsule are composed of, a single layer of flattened epithelial cells resting on a, basement membrane. Basement membrane of the, visceral layer fuses with the basement membrane of, glomerular capillaries on which the capillary endothelial, cells are arranged. Thus, the basement membranes,, which are fused together, form the separation between, the glomerular capillary endothelium and the epithelium, of visceral layer of Bowman capsule., Epithelial cells of the visceral layer fuse with the, basement membrane but the fusion is not complete., Each cell is connected with basement membrane by, cytoplasmic extensions of epithelial cells called pedicles, or feet. These pedicles are arranged in an interdigitating, manner leaving small cleftlike spaces in between. The, cleftlike space is called slit pore. Epithelial cells with, pedicles are called podocytes (Fig. 49.4)., , FIGURE 49.4: Filtering membrane in renal corpuscle. It is, formed by capillary endothelium on one side (red) and visceral, layer of Bowman capsule (yellow) on the other side., , TUBULAR PORTION OF NEPHRON, Tubular portion of nephron is the continuation of Bowman, capsule., It is made up of three parts:, 1. Proximal convoluted tubule, 2. Loop of Henle, 3. Distal convoluted tubule., PROXIMAL CONVOLUTED TUBULE, Proximal convoluted tubule is the coiled portion arising, from Bowman capsule. It is situated in the cortex. It is, continued as descending limb of loop of Henle. Length, of proximal convoluted tubule is 14 mm and the diameter, is 55 µ. Proximal convoluted tubule is continued as loop, of Henle., Functional histology, Proximal convoluted tubule is formed by single layer of, cuboidal epithelial cells. Characteristic feature of these, cells is the presence of hairlike projections directed, towards the lumen of the tubule. Because of the, presence of these projections, the epithelial cells are, called brush-bordered cells., LOOP OF HENLE, Loop of Henle consists of:, i. Descending limb, ii. Hairpin bend, iii. Ascending limb.
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Chapter 49 t Nephron 307, i. Descending Limb, , Thin ascending segment, , Descending limb of loop of Henle is made up of two, segments:, a. Thick descending segment, b. Thin descending segment., , Thin ascending segment is the continuation of hairpin, bend. It is also lined by flattened epithelial cells without, brush border., Total length of thin descending segment, hairpin, bend and thin ascending segment of Henle loop is, 10 mm to 15 mm and the diameter is 15 µ., Thin ascending segment is continued as thick, ascending segment., , Thick descending segment, Thick descending segment is the direct continuation of, the proximal convoluted tubule. It descends down into, medulla. It has a length of 6 mm and a diameter of 55 µ., It is formed by brushbordered cuboidal epithelial cells., Thin descending segment, Thick descending segment is continued as thin des, cending segment (Fig. 49.5). It is formed by flattened, epithelial cells without brush border and it is continued, as hairpin bend of the loop., ii. Hairpin Bend, Hairpin bend formed by flattened epithelial cells without, brush border and it is continued as the ascending limb, of loop of Henle., , Thick ascending segment, Thick ascending segment is about 9 mm long with a, diameter of 30 µ. Thick ascending segment is lined by, cuboidal epithelial cells without brush border., The terminal portion of thick ascending segment,, which runs between the afferent and efferent arterioles, of the same nephrons forms the macula densa. Macula, densa is the part of juxtaglomerular apparatus (Chapter, 50)., Thick ascending segment ascends to the cortex, and continues as distal convoluted tubule., Length and Extent of Loop of Henle, , iii. Ascending Limb, Ascending limb or segment of Henle loop has two, parts:, a. Thin ascending segment, b. Thick ascending segment., , Length and the extent of the loop of Henle vary in, different nephrons:, i. In cortical nephrons, it is short and the hairpin bend, penetrates only up to outer medulla, , FIGURE 49.5: Parts of nephron
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308 Section 5 t Renal Physiology and Skin, TABLE 49.2: Size and cells of different parts of nephron and collecting duct, Segment, , Epithelium, , Length, (mm), , Diameter, (µ), , , , 200, , Bowman Capsule, , Flattened epithelium, , Proximal convoluted tubule, , Cuboidal cells with brush border, , 14, , 55, , Thick descending segment, , Cuboidal cells with brush border, , 6, , 55, , Thin descending segment, hairpin bend, and thin ascending segment, , Flattened epithelium, , Thick ascending segment, , Cuboidal epithelium without brush border, , 9, , 30, , Distal convoluted tubule, , Cuboidal epithelium without brush border, , 14.5 to 15, , 22 to 50, , Collecting duct, , Cuboidal epithelium without brush border, , 20 to 22, , 40 to 200, , ii. In juxtamedullary nephrons, this is long and the, hairpin bend extends deep into the inner medulla., In some nephrons it even runs up to the papilla., DISTAL CONVOLUTED TUBULE, , 10 to 15, , 15, , duct is formed by cuboidal or columnar epithelial, cells., Functional histology, , Distal convoluted tubule is the continuation of thick, ascending segment and occupies the cortex of kidney., It is continued as collecting duct. The length of the distal, convoluted tubule is 14.5 to 15 mm. It has a diameter of, 22 to 50 µ (Table 49.2)., , Collecting duct is formed by two types of epithelial, cells:, 1. Principal or P cells, 2. Intercalated or I cells., These two types of cells have some functional, significance (Chapters 53 and 54)., , Functional histology, , PASSAGE OF URINE, , Distal convoluted tubule is lined by single layer of, cuboidal epithelial cells without brush border. Epithelial, cells in distal convoluted tubule are called intercalated, cells (I cells)., , At the inner zone of medulla, the straight collecting ducts, from each medullary pyramid unite to form papillary, ducts or ducts of Bellini, which open into a ‘V’ shaped, area called papilla. Urine from each medullary pyramid, is collected in the papilla. From here it is drained into a, minor calyx. Three or four minor calyces unite to form, one major calyx. Each kidney has got about 8 minor, calyces and 2 to 3 major calyces., From minor calyces urine passes through major, calyces, which open into the pelvis of the ureter. Pelvis is, the expanded portion of ureter present in the renal sinus., From renal pelvis, urine passes through remaining, portion of ureter and reaches urinary bladder., , COLLECTING DUCT, Distal convoluted tubule continues as the initial or, arched collecting duct, which is in cortex. The lower part, of the collecting duct lies in medulla. Seven to ten initial, collecting ducts unite to form the straight collecting duct,, which passes through medulla., Length of the collecting duct is 20 to 22 mm and, its diameter varies between 40 and 200 µ. Collecting
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310 Section 5 t Renal Physiology and Skin, Glomerular mesangial cells are phagocytic in nature., These cells also secrete glomerular interstitial matrix,, prostaglandins and cytokines., JUXTAGLOMERULAR CELLS, Juxtaglomerular cells are specialized smooth muscle, cells situated in the wall of afferent arteriole just before it, enters the Bowman capsule. These smooth muscle cells, are mostly present in tunica media and tunica adventitia, of the wall of the afferent arteriole., Juxtaglomerular cells are also called granular cells, because of the presence of secretary granules in their, cytoplasm., Polar Cushion or Polkissen, Juxtaglomerular cells form a thick cuff called polar, cushion or polkissen around the afferent arteriole, before it enters the Bowman capsule., , FUNCTIONS OF, JUXTAGLOMERULAR APPARATUS, Primary function of juxtaglomerular apparatus is the, secretion of hormones. It also regulates the glomerular, blood flow and glomerular filtration rate., SECRETION OF HORMONES, Juxtaglomerular apparatus secretes two hormones:, 1. Renin, 2. Prostaglandin., 1. Renin, Juxtaglomerular cells secrete renin. Renin is a peptide, with 340 amino acids. Along with angiotensins, renin, forms the renin-angiotensin system, which is a hormone, system that plays an important role in the maintenance, of blood pressure (Chapter 103)., Stimulants for renin secretion, Secretion of renin is stimulated by four factors:, i. Fall in arterial blood pressure, ii. Reduction in the ECF volume, iii. Increased sympathetic activity, iv. Decreased load of sodium and chloride in, macula densa., Renin-angiotensin system, When renin is released into the blood, it acts on a, specific plasma protein called angiotensinogen or renin, substrate. It is the α2-globulin. By the activity of renin,, the angiotensinogen is converted into a decapeptide, , called angiotensin I. Angiotensin I is converted into, angiotensin II, which is an octapeptide by the activity, of angiotensin-converting enzyme (ACE) secreted, from lungs. Most of the conversion of angiotensin I into, angiotensin II takes place in lungs., Angiotensin II has a short half-life of about 1 to 2, minutes. Then it is rapidly degraded into a heptapeptide, called angiotensin III by angiotensinases, which are, present in RBCs and vascular beds in many tissues., Angiotensin III is converted into angiotensin IV, which is, a hexapeptide (Fig. 50.2)., Actions of Angiotensins, Angiotensin I, Angiotensin I is physiologically inactive and serves only, as the precursor of angiotensin II., Angiotensin II, Angiotensin II is the most active form. Its actions are:, On blood vessels:, i. Angiotensin II increases arterial blood pressure, by directly acting on the blood vessels and, causing vasoconstriction. It is a potent constrictor, of arterioles. Earlier, when its other actions were, not found it was called hypertensin., ii. It increases blood pressure indirectly by, increasing the release of noradrenaline from, postganglionic sympathetic fibers. Noradrenaline, is a general vasoconstrictor (Chapter 71)., On adrenal cortex:, It stimulates zona glomerulosa of adrenal cortex to, secrete aldosterone. Aldosterone acts on renal tubules, and increases retention of sodium, which is also, responsible for elevation of blood pressure., On kidney:, i. Angiotensin II regulates glomerular filtration rate, by two ways:, a. It constricts the efferent arteriole, which, causes decrease in filtration after an initial, increase (Chapter 52), b. It contracts the glomerular mesangial cells, leading to decrease in surface area of, glomerular capillaries and filtration (see, above), ii. It increases sodium reabsorption from renal, tubules. This action is more predominant on, proximal tubules., On brain:, i. Angiotensin II inhibits the baroreceptor reflex, and thereby indirectly increases the blood, pressure. Baroreceptor reflex is responsible for, decreasing the blood pressure (Chapter 103)
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Chapter, , Renal Circulation, , , , , , 51, , INTRODUCTION, RENAL BLOOD VESSELS, MEASUREMENT OF RENAL BLOOD FLOW, REGULATION OF RENAL BLOOD FLOW, , , AUTOREGULATION, , SPECIAL FEATURES OF RENAL CIRCULATION, , INTRODUCTION, Blood vessels of kidneys are highly specialized to, facilitate the functions of nephrons in the formation of, urine. In the adults, during resting conditions both the, kidneys receive 1,300 mL of blood per minute or about, 26% of the cardiac output., Maximum blood supply to kidneys has got the, functional significance. Renal arteries supply blood to, the kidneys., , RENAL BLOOD VESSELS, Renal Artery, Renal artery arises directly from abdominal aorta and, enters the kidney through the hilus. While passing, through renal sinus, the renal artery divides into many, segmental arteries., , FIGURE 51.1: Renal blood vessels, , Arcuate Artery, Each arcuate artery gives rise to interlobular arteries., Interlobular Artery, , Segmental Artery, Segmental artery subdivides into interlobar arteries, (Fig. 51.1)., Interlobar Artery, Interlobar artery passes in between the medullary, pyramids. At the base of the pyramid, it turns and runs, parallel to the base of pyramid forming arcuate artery., , Interlobular arteries run through the renal cortex, perpendicular to arcuate artery. From each interlobular, artery, numerous afferent arterioles arise., Afferent Arteriole, Afferent arteriole enters the Bowman capsule and forms, glomerular capillary tuft. After entering the Bowman, capsule, the afferent arteriole divides into 4 or 5 large, capillaries.
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Chapter 51 t Renal Circulation 313, Glomerular Capillaries, Each large capillary divides into small glomerular, capillaries, which form the loops. And, the capillary, loops unite to form the efferent arteriole, which leaves, the Bowman capsule., Efferent Arteriole, Efferent arterioles form a second capillary network, called peritubular capillaries, which surround the tubular, portions of the nephrons. Thus, the renal circulation, forms a portal system by the presence of two sets of, capillaries namely glomerular capillaries and peritubular, capillaries., , veins, interlobar veins, segmental veins and finally the, renal vein (Fig. 51.3)., Renal vein leaves the kidney through the hilus and, joins inferior vena cava., , MEASUREMENT OF RENAL, BLOOD FLOW, Blood flow to kidneys is measured by using plasma, clearance of para-aminohippuric acid (Refer Chapter 55)., , REGULATION OF RENAL BLOOD FLOW, Renal blood flow is regulated mainly by autoregulation., The nerves innervating renal blood vessels do not have, any significant role in this., , Peritubular Capillaries and Vasa Recta, Peritubular capillaries are found around the tubular, portion of cortical nephrons only. The tubular portion of, juxtamedullary nephrons is supplied by some specialized, capillaries called vasa recta. These capillaries are, straight blood vessels hence the name vasa recta. Vasa, recta arise directly from the efferent arteriole of the, juxtamedullary nephrons and run parallel to the renal, tubule into the medulla and ascend up towards the, cortex (Fig. 51.2)., Venous System, Peritubular capillaries and vasa recta drain into the, venous system. Venous system starts with peritubular, venules and continues as interlobular veins, arcuate, , FIGURE 51.2: Renal capillaries, , FIGURE 51.3: Schematic diagram showing renal blood flow
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314 Section 5 t Renal Physiology and Skin, AUTOREGULATION, Autoregulation is the intrinsic ability of an organ to, regulate its own blood flow (Chapter 102). Autoregulation, is present in some vital organs in the body such as, brain, heart and kidneys. It is highly significant and more, efficient in kidneys., Renal Autoregulation, Renal autoregulation is important to maintain the, glomerular filtration rate (GFR). Blood flow to kidneys, remains normal even when the mean arterial blood, pressure vary widely between 60 mm Hg and 180 mm, Hg. This helps to maintain normal GFR., Two mechanisms are involved in renal autoregulation:, 1. Myogenic response, 2. Tubuloglomerular feedback., 1. Myogenic Response, Whenever the blood flow to kidneys increases, it, stretches the elastic wall of the afferent arteriole., Stretching of the vessel wall increases the flow of, calcium ions from extracellular fluid into the cells. The, influx of calcium ions leads to the contraction of smooth, muscles in afferent arteriole, which causes constriction, of afferent arteriole. So, the blood flow is decreased., 2. Tubuloglomerular Feedback, Macula densa plays an important role in tubuloglomerular, , feedback, which controls the renal blood flow and GFR., Refer Chapter 52 for details., , SPECIAL FEATURES OF, RENAL CIRCULATION, Renal circulation has some special features to cope up, with the functions of the kidneys. Such special features, are:, 1. Renal arteries arise directly from the aorta. So, the, high pressure in aorta facilitates the high blood flow, to the kidneys., 2. Both the kidneys receive about 1,300 mL of blood, per minute, i.e. about 26% of cardiac output. Kidneys, are the second organs to receive maximum blood, flow, the first organ being the liver, which receives, 1,500 mL per minute, i.e. about 30% of cardiac, output., 3. Whole amount of blood, which flows to kidney has, to pass through the glomerular capillaries before, entering the venous system. Because of this, the, blood is completely filtered at the renal glomeruli., 4. Renal circulation has a portal system, i.e. a double, network of capillaries, the glomerular capillaries and, peritubular capillaries., 5. Renal glomerular capillaries form high pressure, bed with a pressure of 60 mm Hg to 70 mm Hg. It is, much greater than the capillary pressure elsewhere, in the body, which is only about 25 mm Hg to 30 mm, Hg. High pressure is maintained in the glomerular, capillaries because the diameter of afferent arteriole, is more than that of efferent arteriole. The high, capillary pressure augments glomerular filtration., 6. Peritubular capillaries form a low pressure bed, with a pressure of 8 mm Hg to 10 mm Hg. This low, pressure helps tubular reabsorption., 7. Autoregulation of renal blood flow is well, established.
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Chapter, , Urine Formation, , 52, , INTRODUCTION, GLOMERULAR FILTRATION, , , , , , , , , INTRODUCTION, METHOD OF COLLECTION OF GLOMERULAR FILTRATE, GLOMERULAR FILTRATION RATE (GFR), FILTRATION FRACTION, PRESSURES DETERMINING FILTRATION, FILTRATION COEFFICIENT, FACTORS REGULATING (AFFECTING) GFR, , TUBULAR REABSORPTION, , , , , , , , , , , INTRODUCTION, METHOD OF COLLECTION OF TUBULAR FLUID, SELECTIVE REABSORPTION, MECHANISM OF REABSORPTION, ROUTES OF REABSORPTION, SITE OF REABSORPTION, REGULATION OF TUBULAR REABSORPTION, THRESHOLD SUBSTANCES, TRANSPORT MAXIMUM – Tm VALUE, REABSORPTION OF IMPORTANT SUBSTANCES, , TUBULAR SECRETION, , , , INTRODUCTION, SUBSTANCES SECRETED IN DIFFERENT SEGMENTS OF RENAL TUBULES, , SUMMARY OF URINE FORMATION, , INTRODUCTION, Urine formation is a blood cleansing function. Normally,, about 1,300 mL of blood (26% of cardiac output) enters, the kidneys. Kidneys excrete the unwanted substances, along with water from the blood as urine. Normal urinary, output is 1 L/day to 1.5 L/day., Processes of Urine Formation, When blood passes through glomerular capillaries, the, plasma is filtered into the Bowman capsule. This process, is called glomerular filtration., , Filtrate from Bowman capsule passes through the, tubular portion of the nephron. While passing through, the tubule, the filtrate undergoes various changes both, in quality and in quantity. Many wanted substances, like glucose, amino acids, water and electrolytes are, reabsorbed from the tubules. This process is called, tubular reabsorption., And, some unwanted substances are secreted into, the tubule from peritubular blood vessels. This process, is called tubular secretion or excretion (Fig. 52.1)., Thus, the urine formation includes three processes:
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316 Section 5 t Renal Physiology and Skin, 2. Basement membrane, Basement membrane of glomerular capillaries and, the basement membrane of visceral layer of Bowman, capsule fuse together. The fused basement membrane, separates the endothelium of glomerular capillary and, the epithelium of visceral layer of Bowman capsule., 3. Visceral layer of Bowman capsule, This layer is formed by a single layer of flattened epi, thelial cells resting on a basement membrane. Each, cell is connected with the basement membrane by, cytoplasmic extensions called pedicles or feet. Epithelial, cells with pedicles are called podocytes (Refer to Fig., 49.4). Pedicles interdigitate leaving small cleftlike, spaces in between. The cleftlike space is called slit, pore or filtration slit. Filtration takes place through, these slit pores., Process of Glomerular Filtration, FIGURE 52.1: Events of urine formation, , A. Glomerular filtration, B. Tubular reabsorption, C. Tubular secretion., Among these three processes filtration is the, function of the glomerulus. Reabsorption and secretion, are the functions of tubular portion of the nephron., , GLOMERULAR FILTRATION, INTRODUCTION, Glomerular filtration is the process by which the blood is, filtered while passing through the glomerular capillaries, by filtration membrane. It is the first process of urine, formation. The structure of filtration membrane is well, suited for filtration., Filtration Membrane, Filtration membrane is formed by three layers:, 1. Glomerular capillary membrane, 2. Basement membrane, 3. Visceral layer of Bowman capsule., 1. Glomerular capillary membrane, Glomerular capillary membrane is formed by single, layer of endothelial cells, which are attached to the, basement membrane. The capillary membrane has, many pores called fenestrae or filtration pores with a, diameter of 0.1 µ., , When blood passes through glomerular capillaries,, the plasma is filtered into the Bowman capsule. All the, substances of plasma are filtered except the plasma, proteins. The filtered fluid is called glomerular filtrate., Ultrafiltration, Glomerular filtration is called ultrafiltration because even, the minute particles are filtered. But, the plasma proteins, are not filtered due to their large molecular size. The, protein molecules are larger than the slit pores present, in the endothelium of capillaries. Thus, the glomerular, filtrate contains all the substances present in plasma, except the plasma proteins., METHOD OF COLLECTION OF, GLOMERULAR FILTRATE, Glomerular filtrate is collected in experimental animals, by micropuncture technique. This technique involves, insertion of a micropipette into the Bowman capsule, and aspiration of filtrate., GLOMERULAR FILTRATION RATE, Glomerular filtration rate (GFR) is defined as the total, quantity of filtrate formed in all the nephrons of both the, kidneys in the given unit of time., Normal GFR is 125 mL/minute or about 180 L/day., FILTRATION FRACTION, Filtration fraction is the fraction (portion) of the renal, plasma, which becomes the filtrate. It is the ratio
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Chapter 52 t Urine Formation 317, between renal plasma flow and glomerular filtration rate., It is expressed in percentage., Filtration fraction =, , GFR, Renal plasma flow, , × 100, , 125 mL/min, , × 100, 650 mL/min, = 19.2%., Normal filtration fraction varies from 15% to 20%., =, , PRESSURES DETERMINING FILTRATION, Pressures, which determine the GFR are:, 1. Glomerular capillary pressure, 2. Colloidal osmotic pressure in the glomeruli, 3. Hydrostatic pressure in the Bowman capsule., These pressures determine the GFR by either, favoring or opposing the filtration., , Net filtration pressure is about 20 mm Hg and, it, varies between 15 and 20 mm Hg., Starling Hypothesis and Starling Forces, Determination of net filtration pressure is based on, Starling hypothesis. Starling hypothesis states that the, net filtration through capillary membrane is proportional, to hydrostatic pressure difference across the membrane, minus oncotic pressure difference. Hydrostatic pressure, within the glomerular capillaries is the glomerular, capillary pressure., All the pressures involved in determination of, filtration are called Starling forces., FILTRATION COEFFICIENT, Filtration coefficient is the GFR in terms of net filtration, pressure. It is the GFR per mm Hg of net filtration, pressure. For example, when GFR is 125 mL/min and, net filtration pressure is 20 mm Hg., , 1. Glomerular Capillary Pressure, , 125 mL, , Glomerular capillary pressure is the pressure exerted, by the blood in glomerular capillaries. It is about 60 mm, Hg and, varies between 45 and 70 mm Hg. Glomerular, capillary pressure is the highest capillary pressure in the, body. This pressure favors glomerular filtration., , Filtration coefficient =, , 2. Colloidal Osmotic Pressure, , 1. Renal Blood Flow, , It is the pressure exerted by plasma proteins in the, glomeruli. The plasma proteins are not filtered through, the glomerular capillaries and remain in the glomerular, capillaries. These proteins develop the colloidal, osmotic pressure, which is about 25 mm Hg. It opposes, glomerular filtration., , It is the most important factor that is necessary for, glomerular filtration. GFR is directly proportional to renal, blood flow. Normal blood flow to both the kidneys is, 1,300 mL/minute. The renal blood flow itself is controlled, by autoregulation. Refer previous chapter for details., , 20 mm Hg, = 6.25 mL/mm Hg, , FACTORS REGULATING (AFFECTING) GFR, , 2. Tubuloglomerular Feedback, 3. Hydrostatic Pressure in Bowman Capsule, It is the pressure exerted by the filtrate in Bowman, capsule. It is also called capsular pressure. It is about, 15 mm Hg. It also opposes glomerular filtration., Net Filtration Pressure, Net filtration pressure is the balance between pressure, favoring filtration and pressures opposing filtration. It, is otherwise known as effective filtration pressure or, , essential filtration pressure., , Net filtration pressure =, , Tubuloglomerular feedback is the mechanism that, regulates GFR through renal tubule and macula densa, (Fig. 52.2). Macula densa of juxtaglomerular apparatus, in the terminal portion of thick ascending limb is sensitive, to the sodium chloride in the tubular fluid., When the glomerular filtrate passes through the, terminal portion of thick ascending segment, macula, densa acts like a sensor. It detects the concentration, of sodium chloride in the tubular fluid and accordingly, alters the glomerular blood flow and GFR. Macula densa, detects the sodium chloride concentration via Na+K+, 2Cl– cotransporter (NKCC2)., When the concentration of sodium chloride, increases in the filtrate, , = 60 – (25 + 15) = 20 mm Hg., , When GFR increases, concentration of sodium chloride, increases in the filtrate. Macula densa releases adenosine
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318 Section 5 t Renal Physiology and Skin, dilatation of afferent arteriole and constriction of efferent, arteriole leads to increase in glomerular blood flow and, GFR., 3. Glomerular Capillary Pressure, Glomerular filtration rate is directly proportional to, glomerular capillary pressure. Normal glomerular, capillary pressure is 60 mm Hg. When glomerular, capillary pressure increases, the GFR also increases., Capillary pressure, in turn depends upon the renal blood, flow and arterial blood pressure., 4. Colloidal Osmotic Pressure, , FIGURE 52.2: Tubuloglomerular feedback., NaCl = Sodium chloride, GFR = Glomerular filtration rate., , from ATP. Adenosine causes constriction of afferent, arteriole. So the blood flow through glomerulus, decreases leading to decrease in GFR. Adenosine acts, on afferent arteriole via adenosine A1 receptors., There are several other factors, which increase or, decrease the sensitivity of tubuloglomerular feedback., Factors increasing the sensitivity of tubuloglo, merular feedback:, i. Adenosine, ii. Thromboxane, iii. Prostaglandin E2, iv. Hydroxyeicosatetranoic acid., Factors decreasing the sensitivity of tubuloglo, merular feedback:, i. Atrial natriuretic peptide, ii. Prostaglandin I2, iii. Cyclic AMP (cAMP), iv. Nitrous oxide., When the concentration of sodium chloride, decreases in the filtrate, When GFR decreases, concentration of sodium chloride, decreases in the filtrate. Macula densa secretes, prostaglandin (PGE2), bradykinin and renin., PGE2 and bradykinin cause dilatation of afferent, arteriole. Renin induces the formation of angiotensin, II, which causes constriction of efferent arteriole. The, , Glomerular filtration rate is inversely proportional, to colloidal osmotic pressure, which is exerted by, plasma proteins in the glomerular capillary blood., Normal colloidal osmotic pressure is 25 mm Hg. When, colloidal osmotic pressure increases as in the case of, dehydration or increased plasma protein level GFR, decreases. When colloidal osmotic pressure is low as in, hypoproteinemia, GFR increases., 5. Hydrostatic Pressure in Bowman Capsule, GFR is inversely proportional to this. Normally, it is 15, mm Hg. When the hydrostatic pressure increases in, the Bowman capsule, it decreases GFR. Hydrostatic, pressure in Bowman capsule increases in conditions, like obstruction of urethra and edema of kidney beneath, renal capsule., 6. Constriction of Afferent Arteriole, Constriction of afferent arteriole reduces the blood flow, to the glomerular capillaries, which in turn reduces, GFR., 7. Constriction of Efferent Arteriole, If efferent arteriole is constricted, initially the GFR, increases because of stagnation of blood in the, capillaries. Later when all the substances are filtered, from this blood, further filtration does not occur. It is, because, the efferent arteriolar constriction prevents, outflow of blood from glomerulus and no fresh blood, enters the glomerulus for filtration., 8. Systemic Arterial Pressure, Renal blood flow and GFR are not affected as long, as the mean arterial blood pressure is in between 60, and 180 mm Hg due to the autoregulatory mechanism, (Chapter 51). Variation in pressure above 180 mm Hg or, below 60 mm Hg affects the renal blood flow and GFR
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Chapter 52 t Urine Formation 319, accordingly, because the autoregulatory mechanism, fails beyond this range., 9. Sympathetic Stimulation, Afferent and efferent arterioles are supplied by, sympathetic nerves. The mild or moderate stimulation, of sympathetic nerves does not cause any significant, change either in renal blood flow or GFR., Strong sympathetic stimulation causes severe, constriction of the blood vessels by releasing the, neurotransmitter substance, noradrenaline. The effect, is more severe on the efferent arterioles than on the, afferent arterioles. So, initially there is increase in, filtration but later it decreases. However, if the stimulation, is continued for more than 30 minutes, there is recovery, of both renal blood flow and GFR. It is because of, reduction in sympathetic neurotransmitter., 10. Surface Area of Capillary Membrane, GFR is directly proportional to the surface area of the, capillary membrane., If the glomerular capillary membrane is affected as, in the cases of some renal diseases, the surface area, for filtration decreases. So there is reduction in GFR., 11. Permeability of Capillary Membrane, GFR is directly proportional to the permeability of, glomerular capillary membrane. In many abnormal, conditions like hypoxia, lack of blood supply, presence, of toxic agents, etc. the permeability of the capillary, membrane increases. In such conditions, even plasma, proteins are filtered and excreted in urine., 12. Contraction of Glomerular Mesangial Cells, Glomerular mesangial cells are situated in between the, glomerular capillaries. Contraction of these cells decrea, ses surface area of capillaries resulting in reduction in, GFR (refer Chapter 51 for details)., 13. Hormonal and Other Factors, Many hormones and other secretory factors alter GFR, by affecting the blood flow through glomerulus., Factors increasing GFR by vasodilatation, i., ii., iii., iv., v., vi., , Atrial natriuretic peptide, Brain natriuretic peptide, cAMP, Dopamine, Endothelialderived nitric oxide, Prostaglandin (PGE2)., , Factors decreasing GFR by vasoconstriction, i., ii., iii., iv., v., vi., , Angiotensin II, Endothelins, Noradrenaline, Plateletactivating factor, Plateletderived growth factor, Prostaglandin (PGF2)., , TUBULAR REABSORPTION, INTRODUCTION, Tubular reabsorption is the process by which water and, other substances are transported from renal tubules, back to the blood. When the glomerular filtrate flows, through the tubular portion of nephron, both quantitative, and qualitative changes occur. Large quantity of water, (more than 99%), electrolytes and other substances, are reabsorbed by the tubular epithelial cells. The, reabsorbed substances move into the interstitial fluid, of renal medulla. And, from here, the substances move, into the blood in peritubular capillaries., Since the substances are taken back into the blood, from the glomerular filtrate, the entire process is called, tubular reabsorption., METHOD OF COLLECTION OF TUBULAR FLUID, There are two methods to collect the tubular fluid for, analysis., 1. Micropuncture Technique, A micropipette is inserted into the Bowman capsule, and different parts of tubular portion in the nephrons, of experimental animals, to collect the fluid. The fluid, samples are analyzed and compared with each other to, assess the changes in different parts of nephron., 2. Stop-flow Method, Ureter is obstructed so that the back pressure rises, and stops the glomerular filtration. The obstruction is, continued for 8 minutes. It causes some changes in the, fluid present in different parts of the tubular portion., Later, the obstruction is released and about 30, samples of 0.5 mL of urine are collected separately at, regular intervals of 30 seconds. The first sample contains, the fluid from collecting duct. Successive samples, contain the fluid from distal convoluted tubule, loops of, Henle and proximal convoluted tubule respectively. All, the samples are analyzed.
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320 Section 5 t Renal Physiology and Skin, SELECTIVE REABSORPTION, , 2. Paracelluar Route, , Tubular reabsorption is known as selective reabsorption, because the tubular cells reabsorb only the substances, necessary for the body. Essential substances such, as glucose, amino acids and vitamins are completely, reabsorbed from renal tubule. Whereas the unwanted, substances like metabolic waste products are not, reabsorbed and excreted through urine., , In this route, the substances move through the, intercellular space., It includes transport of substances from:, i. Tubular lumen into interstitial fluid present in, lateral intercellular space through the tight, junction between the cells, ii. Interstitial fluid into capillary (Fig. 52.3)., , MECHANISM OF REABSORPTION, , SITE OF REABSORPTION, , Basic transport mechanisms involved in tubular, reabsorption are of two types:, 1. Active reabsorption, 2. Passive reabsorption., , Reabsorption of the substances occurs in almost all the, segments of tubular portion of nephron., , 1. Active Reabsorption, , About 7/8 of the filtrate (about 88%) is reabsorbed, in proximal convoluted tubule. The brush border of, epithelial cells in proximal convoluted tubule increases, the surface area and facilitates the reabsorption., Substances reabsorbed from proximal convoluted, tubule are glucose, amino acids, sodium, potassium,, calcium, bicarbonates, chlorides, phosphates, urea, uric, acid and water., , Active reabsorption is the movement of molecules, against the electrochemical (uphill) gradient. It needs, liberation of energy, which is derived from ATP., Substances reabsorbed actively, Substances reabsorbed actively from the renal tubule, are sodium, calcium, potassium, phosphates, sulfates,, bicarbonates, glucose, amino acids, ascorbic acid, uric, acid and ketone bodies., , 1. Substances Reabsorbed from Proximal, Convoluted Tubule, , 2. Substances Reabsorbed from Loop of Henle, , 2. Passive Reabsorption, , Substances reabsorbed from loop of Henle are sodium, and chloride., , Passive reabsorption is the movement of molecules, along the electrochemical (downhill) gradient. This, process does not need energy., , 3. Substances Reabsorbed from Distal, Convoluted Tubule, , Substances reabsorbed passively, , Sodium, calcium, bicarbonate and water are reabsorbed, from distal convoluted tubule., , Substances reabsorbed passively are chloride, urea, and water., ROUTES OF REABSORPTION, , REGULATION OF TUBULAR REABSORPTION, Tubular reabsorption is regulated by three factors:, , Reabsorption of substances from tubular lumen into the, peritubular capillary occurs by two routes:, 1. Trancelluar route, 2. Paracellular route., 1. Transcellular Route, In this route the substances move through the cell., It includes transport of substances from:, a. Tubular lumen into tubular cell through apical, (luminal) surface of the cell membrane, b. Tubular cell into interstitial fluid, c. Interstitial fluid into capillary., , FIGURE 52.3: Routes of reabsorption
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Chapter 52 t Urine Formation 321, 1. Glomerulotubular balance, 2. Hormonal factors, 3. Nervous factors., , 1. Highthreshold substances, 2. Lowthreshold substances, 3. Nonthreshold substances., , 1. Glomerulotubular Balance, , 1. High-threshold Substances, , Glomerulotubular balance is the balance between the, filtration and reabsorption of solutes and water in kidney., When GFR increases, the tubular load of solutes and, water in the proximal convoluted tubule is increased. It, is followed by increase in the reabsorption of solutes and, water. This process helps in the constant reabsorption of, solute particularly sodium and water from renal tubule., , Highthreshold substances are those substances, which, do not appear in urine under normal conditions. The food, substances like glucose, amino acids, acetoacetate, ions and vitamins are completely reabsorbed from, renal tubules and do not appear in urine under normal, conditions. These substances can appear in urine, only, if their concentration in plasma is abnormally high or in, renal diseases when reabsorption is affected. So, these, substances are called highthreshold substances., , Mechanism of glomerulotubular balance, Glomerulotubular balance occurs because of osmotic, pressure in the peritubular capillaries. When GFR increa, ses, more amount of plasma proteins accumulate in the, glomerulus. Consequently, the osmotic pressure increa, ses in the blood by the time it reaches efferent arteriole, and peritubular capillaries. The elevated osmotic pressure, in the peritubular capillaries increases reabsorption of, sodium and water from the tubule into the capillary blood., 2. Hormonal Factors, Hormones, which regulate GFR are listed in Table 52.1., 3. Nervous Factor, Activation of sympathetic nervous system increases the, tubular reabsorption (particularly of sodium) from renal, tubules. It also increases the tubular reabsorption indirectly, by stimulating secretion of renin from juxtaglomerular, cells. Renin causes formation of angiotensin II, which, increases the sodium reabsorption (Chapter 50)., THRESHOLD SUBSTANCES, Depending upon the degree of reabsorption, various, substances are classified into three categories:, , 2. Low-threshold Substances, Lowthreshold substances are the substances, which, appear in urine even under normal conditions. The, substances such as urea, uric acid and phosphate are, reabsorbed to a little extend. So, these substances, appear in urine even under normal conditions., 3. Non-threshold Substances, Nonthreshold substances are those substances,, which are not at all reabsorbed and are excreted in, urine irrespective of their plasma level. The metabolic, end products such as creatinine are the nonthreshold, substances., TRANSPORT MAXIMUM – Tm VALUE, Tubular transport maximum or Tm is the rate at which, the maximum amount of a substance is reabsorbed, from the renal tubule., So, for every actively reabsorbed substance, there, is a maximum rate at which it could be reabsorbed. For, example, the transport maximum for glucose (TmG) is, 375 mg/minute in adult males and about 300 mg/minute, in adult females., , TABLE 52.1: Hormones regulating tubular reabsorption, Hormone, , Action, , Aldosterone, , Increases sodium reabsorption in ascending limb, distal convoluted tubule and collecting duct, , Angiotensin II, , Increases sodium reabsorption in proximal tubule, thick ascending limb, distal tubule and, collecting duct (mainly in proximal convoluted tubule), , Antidiuretic hormone, , Increases water reabsorption in distal convoluted tubule and collecting duct, , Atrial natriuretic factor, , Decreases sodium reabsorption, , Brain natriuretic factor, , Decreases sodium reabsorption, , Parathormone, , Increases reabsorption of calcium, magnesium and hydrogen, Decreases phosphate reabsorption, , Calcitonin, , Decreases calcium reabsorption
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322 Section 5 t Renal Physiology and Skin, Threshold Level in Plasma for Substances, having Tm Value, Renal threshold is the plasma concentration at which, a substance appears in urine. Every substance having, Tm value has also a threshold level in plasma or blood., Below that threshold level, the substance is completely, reabsorbed and does not appear in urine. When the, concentration of that substance reaches the threshold,, the excess amount is not reabsorbed and, so it appears, in urine. This level is called the renal threshold of that, substance., For example, the renal threshold for glucose is 180, mg/dL. That is, glucose is completely reabsorbed from, tubular fluid if its concentration in blood is below 180, mg/dL. So, the glucose does not appear in urine. When, the blood level of glucose reaches 180 mg/dL it is not, reabsorbed completely; hence it appears in urine., REABSORPTION OF IMPORTANT SUBSTANCES, Reabsorption of Sodium, From the glomerular filtrate, 99% of sodium is reabsor, bed. Two thirds of sodium is reabsorbed in proximal, convoluted tubule and remaining one third in other seg, ments (except descending limb) and collecting duct., Sodium reabsorption occurs in three steps:, 1. Transport from lumen of renal tubules into the, tubular epithelial cells, 2. Transport from tubular cells into the interstitial fluid, 3. Transport from interstitial fluid to the blood., 1. Transport from Lumen of Renal Tubules, into the Tubular Epithelial Cells, Active reabsorption of sodium ions from lumen into the, tubular cells occurs by two ways:, i. In exchange for hydrogen ion by antiport (sodium, counterport protein) – in proximal convoluted, tubules, ii. Along with other substances like glucose and, amino acids by symport (sodium cotransport, protein) – in other segments and collecting duct., It is believed that some amount of sodium diffuses, along the electrochemical gradient from lumen into, tubular cell across the luminar membrane. The electro, chemical gradient is developed by sodiumpotassium, pump (see below)., 2. Transport from Tubular Cells into, the Interstitial Fluid, Sodium is pumped outside the cells by sodium, potassium pump. This pump moves three sodium ions, , from the cell into interstitium and two potassium ions, from interstitium into the cell., Tubular epithelial cells are connected with their, neighboring cells by tight junctions at their apical luminal, edges. But, beyond the tight junction, a small space, is left between the adjoining cells along their lateral, borders. This space is called lateral intercellular space., The interstitium extends into this space., Most of the sodium ions are pumped into the lateral, intercellular space by sodiumpotassium pump. The rest, of the sodium ions are pumped into the interstitium by, the sodiumpotassium pump situated at the basal part, of the cell membrane., (Transport of sodium out of the tubular cell by sodium, potassium pump, decreases the sodium concentration, within the cell. This develops an electrochemical gradient, between the lumen and tubular cell resulting in diffusion, of sodium into the cell)., 3. Transport from Interstitial Fluid to the Blood, From the interstitial fluid, sodium ions enter the, peritubular capillaries by concentration gradient., In the distal convoluted tubule, the sodium re, absorption is stimulated by the hormone aldosterone, secreted by adrenal cortex., Reabsorption of Water, Reabsorption of water occurs from proximal and distal, convoluted tubules and in collecting duct., Reabsorption of water from proximal convoluted, tubule – obligatory water reabsorption, Obligatory reabsorption is the type of water reabsorption, in proximal convoluted tubule, which is secondary, (obligatory) to sodium reabsorption. When sodium, is reabsorbed from the tubule, the osmotic pressure, decreases. It causes osmosis of water from renal, tubule., Reabsorption of water from distal convoluted tubule, and collecting duct – facultative water reabsorption, Facultative reabsorption is the type of water reabsorption, in distal convoluted tubule and collecting duct that, occurs by the activity of antidiuretic hormone (ADH)., Normally, the distal convoluted tubule and the collecting, duct are not permeable to water. But in the presence of, ADH, these segments become permeable to water, so, it is reabsorbed., Mechanism of action of ADH – Aquaporins, Antidiuretic hormone increases water reabsorption, in distal convoluted tubules and collecting ducts by
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Chapter 52 t Urine Formation 323, stimulating the water channels called aquaporins. ADH, combines with vasopressin (V2) receptors in the tubular, epithelial membrane and activates adenyl cyclase,, to form cyclic AMP. This cyclic AMP activates the, aquaporins, which increase the water reabsorption., Aquaporins (AQP) are the membrane proteins,, which function as water channels. Though about 10, aquaporins are identified in mammals only 5 are found, in humans. Aquaporin1, 2 and 3 are present in renal, tubules. Aquaporin4 is present in brain and aquaporin5, is found in salivary glands. Aquaporin2 forms the water, channels in renal tubules., Reabsorption of Glucose, Glucose is completely reabsorbed in the proximal, convoluted tubule. It is transported by secondary active, transport (sodium cotransport) mechanism. Glucose and, sodium bind to a common carrier protein in the luminal, membrane of tubular epithelium and enter the cell. The, carrier protein is called sodium-dependant glucose, cotransporter 2 (SGLT2). From tubular cell glucose is, transported into medullary interstitium by another carrier, protein called glucose transporter 2 (GLUT2)., Tubular maximum for glucose (TmG), In adult male, TmG is 375 mg/minute and in adult, females it about 300 mg/minute., Renal threshold for glucose, Renal threshold for glucose is 180 mg/dL in venous, blood. When the blood level reaches 180 mg/dL glucose, is not reabsorbed completely and appears in urine., Splay, Splay means deviation. With normal GFR of 125 mL/, minute and TmG of 375 mg/minute in an adult male the, predicted (expected) renal threshold for glucose should, be 300 mg/dL. But actually it is only 180 mg/dL., When the renal threshold curves are drawn by using, these values, the actual curve deviates from the ‘should, be’ or predicted or ideal curve (Fig. 52.4). This type of, deviation is called splay. Splay is because of the fact, that all the nephrons do not have the same filtering and, reabsorbing capacities., Reabsorption of Amino Acids, Amino acids are also reabsorbed completely in proximal, convoluted tubule. Amino acids are reabsorbed actively, by the secondary active transport mechanism along, with sodium., , FIGURE 52.4: Splay in renal threshold curve for glucose, , Reabsorption of Bicarbonates, Bicarbonate is reabsorbed actively, mostly in proximal, tubule (Chapter 54). It is reabsorbed in the form of, carbon dioxide., Bicarbonate is mostly present as sodium bicarbonate, in the filtrate. Sodium bicarbonate dissociates into sodium, and bicarbonate ions in the tubular lumen. Sodium, diffuses into tubular cell in exchange of hydrogen., Bicarbonate combines with hydrogen to form carbonic, acid. Carbonic acid dissociates into carbon dioxide and, water in the presence of carbonic anhydrase. Carbon, dioxide and water enter the tubular cell., In the tubular cells, carbon dioxide combines with, water to form carbonic acid. It immediately dissociates, into hydrogen and bicarbonate. Bicarbonate from the, tubular cell enters the interstitium. There it combines, with sodium to form sodium bicarbonate (Fig. 54.1)., , TUBULAR SECRETION, INTRODUCTION, Tubular secretion is the process by which the substances, are transported from blood into renal tubules. It is also, called tubular excretion. In addition to reabsorption from, renal tubules, some substances are also secreted into, the lumen from the peritubular capillaries through the, tubular epithelial cells., Dye phenol red was the first substance found to be, secreted in renal tubules in experimental conditions., Later many other substances were found to be secreted.
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324 Section 5 t Renal Physiology and Skin, Such substances are:, 1. Paraaminohippuric acid (PAH), 2. Diodrast, 3. 5hydroxyindoleacetic acid (5HIAA), 4. Amino derivatives, 5. Penicillin., , Thus, urine is formed in nephron by the processes of, glomerular filtration, selective reabsorption and tubular, secretion., , SUBSTANCES SECRETED IN DIFFERENT, SEGMENTS OF RENAL TUBULES, , 1. Glomerular filtration, , 1. Potassium is secreted actively by sodiumpotassium, pump in proximal and distal convoluted tubules and, collecting ducts, 2. Ammonia is secreted in the proximal convoluted, tubule, 3. Hydrogen ions are secreted in the proximal and, distal convoluted tubules. Maximum hydrogen ion, secretion occurs in proximal tubule, 4. Urea is secreted in loop of Henle., , SUMMARY OF URINE FORMATION, Urine formation takes place in three processes (Refer, to Fig. 52.1):, , Plasma is filtered in glomeruli and the substances reach, the renal tubules along with water as filtrate., 2. Tubular Reabsorption, The 99% of filtrate is reabsorbed in different segments, of renal tubules., 3. Tubular Secretion, Some substances are transported from blood into the, renal tubule., With all these changes, the filtrate becomes urine.
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Concentration of Urine, , , , , , , , Chapter, , 53, , INTRODUCTION, MEDULLARY GRADIENT, COUNTERCURRENT MECHANISM, ROLE OF ADH, SUMMARY OF URINE CONCENTRATION, APPLIED PHYSIOLOGY, , INTRODUCTION, Every day 180 L of glomerular filtrate is formed with large, quantity of water. If this much of water is excreted in, urine, body will face serious threats. So the concentration, of urine is very essential., Osmolarity of glomerular filtrate is same as that of, plasma and it is 300 mOsm/L. But, normally urine is, concentrated and its osmolarity is four times more than, that of plasma, i.e. 1,200 mOsm/L., Osmolarity of urine depends upon two factors:, 1. Water content in the body, 2. Antidiuretic hormone (ADH)., Mechanism of urine formation is the same for, dilute urine and concentrated urine till the fluid reaches, the distal convoluted tubule. However, dilution or, concentration of urine depends upon water content of, the body., FORMATION OF DILUTE URINE, When, water content in the body increases, kidney, excretes dilute urine. This is achieved by inhibition of, ADH secretion from posterior pituitary (Chapter 66)., So water reabsorption from renal tubules does not, take place (see Fig. 53.4) leading to excretion of large, amount of water. This makes the urine dilute., FORMATION OF CONCENTRATED URINE, When the water content in body decreases, kidney, retains water and excretes concentrated urine. Forma, , tion of concentrated urine is not as simple as that of, dilute urine., It involves two processes:, 1. Development and maintenance of medullary, gradient by countercurrent system, 2. Secretion of ADH., , MEDULLARY GRADIENT, MEDULLARY HYPEROSMOLARITY, Cortical interstitial fluid is isotonic to plasma with the, osmolarity of 300 mOsm/L. Osmolarity of medullary, interstitial fluid near the cortex is also 300 mOsm/L., However, while proceeding from outer part towards, the inner part of medulla, the osmolarity increases, gradually and reaches the maximum at the inner most, part of medulla near renal sinus. Here, the interstitial, fluid is hypertonic with osmolarity of 1,200 mOsm/L (Fig., 53.1)., This type of gradual increase in the osmolarity of, the medullary interstitial fluid is called the medullary, gradient. It plays an important role in the concentration, of urine., DEVELOPMENT AND MAINTENANCE OF, MEDULLARY GRADIENT, Kidney has some unique mechanism called counter, current mechanism, which is responsible for the develop, ment and maintenance of medullary gradient and hyper, osmolarity of interstitial fluid in the inner medulla.
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326 Section 5 t Renal Physiology and Skin, Role of Loop of Henle in Development, of Medullary Gradient, Loop of Henle of juxtamedullary nephrons plays a major, role as countercurrent multiplier because loop of these, nephrons is long and extends upto the deeper parts of, medulla., Main reason for the hyperosmolarity of medullary, interstitial fluid is the active reabsorption of sodium, chloride and other solutes from ascending limb of Henle, loop into the medullary interstitium. These solutes, accumulate in the medullary interstitium and increase, the osmolarity., Now, due to the concentration gradient, the sodium, and chlorine ions diffuse from medullary interstitium, into the descending limb of Henle loop and reach the, ascending limb again via hairpin bend., Thus, the sodium and chlorine ions are repeatedly re, circulated between the descending limb and ascending, limb of Henle loop through medullary interstitial fluid, leaving a small portion to be excreted in the urine., Apart from this there is regular addition of more and, more new sodium and chlorine ions into descending, limb by constant filtration. Thus, the reabsorption of, sodium chloride from ascending limb and addition of, new sodium chlorine ions into the filtrate increase or, multiply the osmolarity of medullary interstitial fluid and, medullary gradient. Hence, it is called countercurrent, multiplier., , FIGURE 53.1: Countercurrent multiplier., Numerical indicate osmolarity (mOsm/L), , Other Factors Responsible for Hyperosmolarity, of Medullary Interstitial Fluid, , COUNTERCURRENT MECHANISM, , In addition to countercurrent multiplier action provided, by the loop of Henle, two more factors are involved in, hyperosmolarity of medullary interstitial fluid., , COUNTERCURRENT FLOW, , i. Reabsorption of sodium from collecting duct, , A countercurrent system is a system of ‘U’shaped, tubules (tubes) in which, the flow of fluid is in opposite, direction in two limbs of the ‘U’shaped tubules., , Reabsorption of sodium from medullary part of collect, ing duct into the medullary interstitium, adds to the, osmolarity of inner medulla., ii. Recirculation of urea, , Divisions of Countercurrent System, Countercurrent system has two divisions:, 1. Countercurrent multiplier formed by loop of Henle, 2. Countercurrent exchanger formed by vasa recta., COUNTERCURRENT MULTIPLIER, Loop of Henle, Loop of Henle functions as countercurrent multiplier. It, is responsible for development of hyperosmolarity of, medullary interstitial fluid and medullary gradient., , Fifty percent of urea filtered in glomeruli is reabsorbed, in proximal convoluted tubule. Almost an equal amount, of urea is secreted in the loop of Henle. So the fluid in, distal convoluted tubule has as much urea as amount, filtered., Collecting duct is impermeable to urea. However,, due to the water reabsorption from distal convoluted, tubule and collecting duct in the presence of ADH, urea, concentration increases in collecting duct. Now due to, concentration gradient, urea diffuses from inner medullary, part of collecting duct into medullary interstitium.
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Chapter 53 t Concentration of Urine 327, Due to continuous diffusion, the concentration, of urea increases in the inner medulla resulting in, hyperosmolarity of interstitium in inner medulla., Again, by concentration gradient, urea enters the, ascending limb. From here, it passes through distal, convoluted tubule and reaches the collecting duct. Urea, enters the medullary interstitium from collecting duct. By, this way urea recirculates repeatedly and helps to maintain, the hyperosmolarity of inner medullary interstitium. Only, a small amount of urea is excreted in urine., Urea recirculation accounts for 50% of hyper, osmolarity in inner medulla. Diffusion of urea from, collecting duct into medullary interstitium is carried out, by urea transporters, UTA1 and UTA3, which are, activated by ADH., COUNTERCURRENT EXCHANGER, Vasa Recta, Vasa recta functions as countercurrent exchanger. It is, responsible for the maintenance of medullary gradient,, which is developed by countercurrent multiplier (Fig., 53.2)., Role of Vasa Recta in the Maintenance, of Medullary Gradient, Vasa recta acts like countercurrent exchanger because, of its position. It is also ‘U’shaped tubule with a, descending limb, hairpin bend and an ascending limb., Vasa recta runs parallel to loop of Henle. Its descending, limb runs along the ascending limb of Henle loop and, its ascending limb runs along with descending limb of, Henle loop., The sodium chloride reabsorbed from ascending, limb of Henle loop enters the medullary interstitium., From here it enters the descending limb of vasa recta., Simultaneously water diffuses from descending limb of, vasa recta into medullary interstitium., The blood flows very slowly through vasa recta., So, a large quantity of sodium chloride accumulates, in descending limb of vasa recta and flows slowly, towards ascending limb. By the time the blood reaches, the ascending limb of vasa recta, the concentration, of sodium chloride increases very much. This causes, diffusion of sodium chloride into the medullary interstitium., Simultaneously, water from medullary interstitium, enters the ascending limb of vasa recta. And the cycle, is repeated., If the vasa recta would be a straight vessel without, hairpin arrangement, blood would leave the kidney, quickly at renal papillary level. In that case, the blood, would remove all the sodium chloride from medullary, , FIGURE 53.2: Countercurrent exchanger., Numerical indicate osmolarity (mOsm/L), , interstitium and thereby the hyperosmolarity will be, decreased. However, this does not happen, since the, vasa recta has a hairpin bend., Therefore, when blood passes through the, ascending limb of vasa recta, sodium chloride diffuses, out of blood and enters the interstitial fluid of medulla, and, water diffuses into the blood., Thus, vasa recta retains sodium chloride in the, medullary interstitium and removes water from it. So, the, hyperosmolarity of medullary interstitium is maintained., The blood passing through the ascending limb of vasa, recta may carry very little amount of sodium chloride, from the medulla., Recycling of urea also occurs through vasa recta., From medullary interstitium, along with sodium chloride,, urea also enters the descending limb of vasa recta., When blood passes through ascending limb of vasa
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328 Section 5 t Renal Physiology and Skin, recta, urea diffuses back into the medullary interstitium, along with sodium chloride., Thus, sodium chloride and urea are exchanged for, water between the ascending and descending limbs of, vasa recta, hence this system is called countercurrent, exchanger., , ROLE OF ADH, Final concentration of urine is achieved by the action, of ADH. Normally, the distal convoluted tubule and, collecting duct are not permeable to water. But the, presence of ADH makes them permeable, resulting, in water reabsorption. Water reabsorption induced by, ADH is called facultative reabsorption of water (Refer, Chapter 52 for details)., A large quantity of water is removed from the fluid, while passing through distal convoluted tubule and, collecting duct. So, the urine becomes hypertonic with, an osmolarity of 1,200 mOsm/L (Fig. 53.3)., , FIGURE 53.3: Role of ADH in the formation of concentrated, urine. ADH increases the permeability for water in distal, convoluted tubule and collecting duct. Numerical indicate, osmolarity (mOsm/L), , SUMMARY OF URINE CONCENTRATION, When the glomerular filtrate passes through renal, tubule, its osmolarity is altered in different segments as, described below (Fig. 53.4)., 1. BOWMAN CAPSULE, Glomerular filtrate collected at the Bowman capsule is, isotonic to plasma. This is because it contains all the, substances of plasma except proteins. Osmolarity of, the filtrate at Bowman capsule is 300 mOsm/L., 2. PROXIMAL CONVOLUTED TUBULE, When the filtrate flows through proximal convoluted, tubule, there is active reabsorption of sodium and, chloride followed by obligatory reabsorption of water., , FIGURE 53.4: Mechanism for the formation of dilute urine., Numerical indicate osmolarity (mOsm/L)
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Chapter 53 t Concentration of Urine 329, So, the osmolarity of fluid remains the same as in the, case of Bowman capsule, i.e. 300 mOsm/L. Thus, in, proximal convoluted tubules, the fluid is isotonic to, plasma., , 3. THICK DESCENDING SEGMENT, When the fluid passes from proximal convoluted tubule, into the thick descending segment, water is reabsorbed, from tubule into outer medullary interstitium by means, of osmosis. It is due to the increased osmolarity in the, medullary interstitium, i.e. outside the thick descending, tubule. The osmolarity of the fluid inside this segment is, between 450 and 600 mOsm/L. That means the fluid is, slightly hypertonic to plasma., 4. THIN DESCENDING SEGMENT, OF HENLE LOOP, As the thin descending segment of Henle loop passes, through the inner medullary interstitium (which is, increasingly hypertonic) more water is reabsorbed., This segment is highly permeable to water and so the, osmolarity of tubular fluid becomes equal to that of the, surrounding medullary interstitium., In the short loops of cortical nephrons, the osmolarity, of fluid at the hairpin bend of loop becomes 600 mOsm/L., And, in the long loops of juxtamedullary nephrons, at, the hairpin bend, the osmolarity is 1,200 mOsm/L. Thus, in this segment the fluid is hypertonic to plasma., 5. THIN ASCENDING SEGMENT, OF HENLE LOOP, When the thin ascending segment of the loop ascends, upwards through the medullary region, osmolarity, decreases gradually., Due to concentration gradient, sodium chloride, diffuses out of tubular fluid and osmolarity decreases, to 400 mOsm/L. The fluid in this segment is slightly, , between 150 and 200 mOsm/L. The fluid inside becomes, hypotonic to plasma., , 7. DISTAL CONVOLUTED TUBULE AND, COLLECTING DUCT, In the presence of ADH, distal convoluted tubule and, collecting duct become permeable to water resulting in, water reabsorption and final concentration of urine. It is, found that in the collecting duct, Principal (P) cells are, responsible for ADH induced water reabsorption., Reabsorption of large quantity of water increases, the osmolarity to 1,200 mOsm/L (Fig. 53.3). The urine, becomes hypertonic to plasma., , APPLIED PHYSIOLOGY, 1. Osmotic Diuresis, Diuresis is the excretion of large quantity of water through, urine. Osmotic diuresis is the diuresis induced by the, osmotic effects of solutes like glucose. It is common in, diabetes mellitus (Chapter 69)., 2. Polyuria, Polyuria is the increased urinary output with frequent, voiding. It is common in diabetes insipidus. In this, disorder, the renal tubules fail to reabsorb water because, of ADH deficiency (Chapter 66)., 3. Syndrome of Inappropriate Hypersecretion, of ADH (SIADH), It is a pituitary disorder characterized by hypersecretion of, ADH is the SIADH. Excess ADH causes water retention,, which decreases osmolarity of ECF (Chapter 66)., 4. Nephrogenic Diabetes Insipidus, , hypertonic to plasma., , Sometimes, ADH secretion is normal but the renal, tubules fail to give response to ADH resulting in polyuria., This condition is called nephrogenic diabetes insipidus., , 6. THICK ASCENDING SEGMENT, , 5. Bartter Syndrome, , This segment is impermeable to water. But there is, active reabsorption of sodium and chloride from this., Reabsorption of sodium decreases the osmolarity, of tubular fluid to a greater extent. The osmolarity is, , Bartter syndrome is a genetic disorder characterized, by defect in the thick ascending segment. This causes, decreased sodium and water reabsorption resulting in, loss of sodium and water through urine.
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Acidification of Urine, and Role of Kidney in, Acid-base Balance, , Chapter, , 54, , INTRODUCTION, REABSORPTION OF BICARBONATE IONS, SECRETION OF HYDROGEN IONS, , , , SODIUM-HYDROGEN ANTIPORT PUMP, ATP-DRIVEN PROTON PUMP, , REMOVAL OF HYDROGEN IONS AND ACIDIFICATION OF URINE, , , , , BICARBONATE MECHANISM, PHOSPHATE MECHANISM, AMMONIA MECHANISM, , APPLIED PHYSIOLOGY, , INTRODUCTION, Kidney plays an important role in maintenance of acidbase balance by excreting hydrogen ions and retaining, bicarbonate ions., Normally, urine is acidic in nature with a pH of 4.5 to, 6. Metabolic activities in the body produce large quantity, of acids (with lot of hydrogen ions), which threaten to, push the body towards acidosis., However, kidneys prevent this by two ways:, 1. Reabsorption of bicarbonate ions (HCO3–), 2. Secretion of hydrogen ions (H+)., , REABSORPTION OF BICARBONATE IONS, About 4,320 mEq of HCO3– is filtered by the glomeruli, everyday. It is called filtered load of HCO3–. Excretion, of this much HCO3– in urine will affect the acid-base, balance of body fluids. So, HCO3– must be taken back, from the renal tubule by reabsorption., , SECRETION OF HYDROGEN IONS, Reabsorption of filtered HCO3– occurs by the secretion, of H+ in the renal tubules. About 4,380 mEq of H+ appear, every day in the renal tubule by means of filtration and, secretion. Not all the H+ are excreted in urine. Out of, 4,380 mEq, about 4,280 to 4,330 mEq of H+ is utilized, , for the reabsorption of filtered HCO3–. Only the remaining, 50 to 100 mEq is excreted. It results in the acidification, of urine., Secretion of H+ into the renal tubules occurs by the, formation of carbonic acid. Carbon dioxide formed in the, tubular cells or derived from tubular fluid combines with, water to form carbonic acid in the presence of carbonic, anhydrase. This enzyme is available in large quantities, in the epithelial cells of the renal tubules. The carbonic, acid immediately dissociates into H+ and HCO3– (Fig., 54.1)., H+ is secreted into the lumen of proximal convoluted, tubule, distal convoluted tubule and collecting duct., Distal convoluted tubule and collecting duct have a, special type of cells called intercalated cells (I cells), that are involved in handling hydrogen and bicarbonate, ions., Secretion of H+ occurs by two pumps:, i. Sodium-hydrogen antiport pump, ii. ATP-driven proton pump., SODIUM-HYDROGEN ANTIPORT PUMP, When sodium ion (Na+) is reabsorbed from the tubular, fluid into the tubular cell, H+ is secreted from the cell, into the tubular fluid in exchange for Na+. The sodiumhydrogen antiport pump present in the tubular cells
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Chapter 54 t Acidification of Urine and Role of Kidney in Acid-base Balance 331, is responsible for the exchange of Na+ and H+. This, type of sodium-hydrogen counter transport occurs, predominantly in distal convoluted tubule (Table 54.1)., ATP-DRIVEN PROTON PUMP, This is an additional pump for H+ secretion in distal, convoluted tubule and collecting duct. This pump, operates by energy from ATP., , REMOVAL OF HYDROGEN IONS AND, ACIDIFICATION OF URINE, Role of Kidney in Preventing Metabolic Acidosis, Kidney plays an important role in preventing metabolic, acidosis (Chapter 5) by excreting H+., , Excretion of H+ occurs by three mechanisms:, 1. Bicarbonate mechanism, 2. Phosphate mechanism, 3. Ammonia mechanism., BICARBONATE MECHANISM, All the filtered HCO3– in the renal tubules is reabsorbed., About 80% of it is reabsorbed in proximal convoluted, tubule, 15% in Henle loop and 5% in distal convoluted, tubule and collecting duct. The reabsorption of HCO3–, utilizes the H+ secreted into the renal tubules., H+ secreted into the renal tubule, combines with, filtered HCO3– forming carbonic acid (H2CO3). Carbonic, acid dissociates into carbon dioxide and water in the, presence of carbonic anhydrase. Carbon dioxide and, water enter the tubular cell., In the tubular cells, carbon dioxide combines with, water to form carbonic acid. It immediately dissociates, into H+ and HCO3–. HCO3– from the tubular cell enters, the interstitium. Simultaneously Na+ is reabsorbed from, the renal tubule under the influence of aldosterone., HCO3– combines with Na+ to form sodium bicarbonate, (NaHCO3). Now, the H+ is secreted into the tubular, lumen from the cell in exchange for Na+ (Fig. 54.1)., Thus, for every hydrogen ion secreted into lumen, of tubule, one bicarbonate ion is reabsorbed from the, tubule. In this way, kidneys conserve the HCO3–. The, reabsorption of filtered HCO3– is an important factor in, maintaining pH of the body fluids., PHOSPHATE MECHANISM, , FIGURE 54.1: Reabsorption of bicarbonate ions by secretion, of hydrogen ions in renal tubule. P = sodium-hydrogen antiport, pump, TABLE 54.1: Mechanisms involved in secretion of, hydrogen ions in renal tubule, Mechanism, , Segment of renal tubule, , Sodium-hydrogen pump, , Distal convoluted tubule, , ATP-driven proton pump, , Distal convoluted tubule, Collecting duct, , Bicarbonate mechanism, , Proximal convoluted tubule, Henle loop, Distal convoluted tubule, , Phosphate mechanism, , Distal convoluted tubule, Collecting duct, , Ammonia mechanism, , Proximal convoluted tubule., , In the tubular cells, carbon dioxide combines with water, to form carbonic acid. It immediately dissociates into, H+ and HCO3–. HCO3– from the tubular cell enters the, interstitium. Simultaneously, Na+ is reabsorbed from, renal tubule under the influence of aldosterone. Na+, enters the interstitium and combines with HCO3–. H+ is, secreted into the tubular lumen from the cell in exchange, for Na+ (Fig. 54.2)., H+, which is secreted into renal tubules, reacts, with phosphate buffer system. It combines with sodium, hydrogen phosphate to form sodium dihydrogen, phosphate. Sodium dihydrogen phosphate is excreted, in urine. The H+, which is added to urine in the form of, sodium dihydrogen, makes the urine acidic. It happens, mainly in distal tubule and collecting duct because of, the presence of large quantity of sodium hydrogen, phosphate in these segments.
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332 Section 5 t Renal Physiology and Skin, , FIGURE 54.2: Excretion of hydrogen ions, in combination with phosphate ions, , AMMONIA MECHANISM, This is the most important mechanism by which kidneys, excrete H+ and make the urine acidic. In the tubular, epithelial cells, ammonia is formed when the amino, acid glutamine is converted into glutamic acid in the, presence of the enzyme glutaminase. Ammonia is also, formed by the deamination of some of the amino acids, such as glycine and alanine (Fig. 54.3)., Ammonia (NH3) formed in tubular cells is secreted, into tubular lumen in exchange for sodium ion. Here,, it combines with H+ to form ammonium (NH4). The, tubular cell membrane is not permeable to ammonium., Therefore, it remains in the lumen and then excreted, into urine. Thus, H+ is added to urine in the form of, , FIGURE 54.3: Excretion of hydrogen ions, in combination with ammonia, , ammonium compounds resulting in acidification of urine., For each NH4 excreted one HCO3– is added to interstitial, fluid., This process takes place mostly in the proximal, convoluted tubule because glutamine is converted into, ammonia in the cells of this segment., Thus, by excreting H+ and conserving HCO3–,, kidneys produce acidic urine and help to maintain the, acid-base balance of body fluids., , APPLIED PHYSIOLOGY, Metabolic acidosis occurs when kidneys fail to excrete, metabolic acids. Metabolic alkalosis occurs when, kidneys excrete large quantity of hydrogen. Refer, Chapter 5 for details.
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Renal Function Tests, , Chapter, , 55, , PROPERTIES AND COMPOSITION OF NORMAL URINE, , , , PROPERTIES OF URINE, COMPOSITION OF URINE, , RENAL FUNCTION TESTS, , , , , , EXAMINATION OF URINE – URINALYSIS, PHYSICAL EXAMINATION, MICROSCOPIC EXAMINATION, CHEMICAL ANALYSIS, , EXAMINATION OF BLOOD, EXAMINATION OF BLOOD AND URINE, , PROPERTIES AND COMPOSITION, OF NORMAL URINE, PROPERTIES OF URINE, Volume, Reaction, Specific gravity, Osmolarity, Color, Odor, , :, :, :, :, :, :, , 1,000 to 1,500 mL/day, Slightly acidic with pH of 4.5 to 6, 1.010 to 1.025, 1,200 mOsm/L, Normally, straw colored, Fresh urine has light aromatic odor., If stored for some time, the odor, becomes stronger due to bacterial, decomposition., , COMPOSITION OF URINE, Urine consists of water and solids. Solids include organic, and inorganic substances (Fig. 55.1)., , RENAL FUNCTION TESTS, Renal function tests are the group of tests that are, performed to assess the functions of kidney., Renal function tests are of three types:, A. Examination of urine alone, , FIGURE 55.1: Quantity of solids excreted in urine, (mMols/day), , B. Examination of blood alone, C. Examination of blood and urine., EXAMINATION OF URINE – URINALYSIS, Routine examination of urine or urinalysis is a group of, diagnostic tests performed on the sample of urine., Urinalysis is done by:, i. Physical examination, ii. Microscopic examination, iii. Chemical analysis.
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334 Section 5 t Renal Physiology and Skin, PHYSICAL EXAMINATION, , 3. Epithelial Cells, , 1. Volume, , Normally few tubular epithelial cells slough into urine., Presence of many epithelial cells suggests nephrotic, syndrome and tubular necrosis., , Increase in urine volume indicates increase in protein, catabolism and renal disorders such as chronic renal, failure, diabetes insipidus and glycosuria., 2. Color, Normally urine is straw colored. Abnormal coloration of, urine is due to several causes such as jaundice, hema, turia, hemoglobinuria, medications, excess urobilino, gen, ingestion of beetroot or color added to food., 3. Appearance, Normally urine is clear. It becomes turbid in both, physiological and pathological conditions. Physiological, conditions causing turbidity of urine are precipitation, of crystals, presence of mucus or vaginal discharge., Pathological conditions causing turbidity are presence, of blood cells, bacteria or yeast., 4. Specific Gravity, Specific gravity of urine is the measure of dissolved, solutes (particles) in urine. It is low in diabetes insipidus, and high in diabetes mellitus, acute renal failure and, excess medications., 5. Osmolarity, Osmolarity of urine decreases in diabetes insipidus., 6. pH and Reaction, Measurement of pH is useful in determining the metabolic, or respiratory acidosis or alkalosis. The pH decreases, in renal diseases. In normal conditions, pH of urine, depends upon diet. It is slightly alkaline in vegetarians, and acidic in non-vegetarians., MICROSCOPIC EXAMINATION, Microscopic examination of centrifuged sediment of, urine is useful in determining the renal diseases., , 4. Casts, Casts are the cylindrical bodies that are casted (molded), in the shape of renal tubule. Casts may be hyaline,, granular or cellular in nature. Hyaline and granular, casts, which are formed by precipitation of proteins may, appear in urine in small numbers. The number increases, in proteinuria due to glomerulonephritis., Cellular casts are formed by sticking together of, some cells. Red blood cell casts appear in urine during, glomerulonephritis and tubular necrosis. White blood, cell casts appear in pyelonephritis. Epithelial casts are, formed during acute tubular necrosis., 5. Crystals, Several types of crystals are present in normal urine., Common crystals are the crystals of calcium oxalate,, calcium phosphate, uric acid and triple phosphate, (calcium, ammonium and magnesium)., Abnormal crystals such as crystals of cystine and, tyrosine appear in liver diseases., 6. Bacteria, Bacteria are common in urine specimens because of, normal microbial flora of urinary tract, urethra and, vagina and because of their ability to multiply rapidly in, urine. Culture studies are necessary to determine the, presence of bacteria in urine., CHEMICAL ANALYSIS, Chemical analysis of urine helps to determine the, presence of abnormal constituents of urine or presence, of normal constituents in abnormal quantity. Both the, findings reveal the presence of renal abnormality., Following are the common chemical tests of urine:, 1. Glucose, , Presence of red blood cells in urine indicates glomerular, disease such as glomerulonephritis., , Glucose appears in urine when the blood glucose level, increases above 180 mg/dL. Glycosuria (presence of, glucose in urine) may be the first indicator of diabetes, mellitus., , 2. White Blood Cells, , 2. Protein, , Normally few white blood cells appear in high power field., The number increases in acute glomerulonephritis,, infection of urinary tract, vagina or cervix., , Presence of excess protein (proteinuria) particularly, albumin (albuminuria) in urine indicates renal diseases., Urinary excretion of albumin in a normal healthy adult, , 1. Red Blood Cells
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Chapter 55 t Renal Function Tests 335, is about 30 mg/day. It exceeds this level in glomerulonephritis. It also increases in fever and severe exercise., 3. Ketone Bodies, Ketonuria (presence of ketone bodies in urine) occurs in, pregnancy, fever, diabetes mellitus, prolonged starvation, and glycogen storage diseases., , Uric acid, : 2.5 mg/dL, Creatinine, : 0.5 to 1.5 mg/dL, The blood level of these substances increases in, renal failure., , EXAMINATION OF BLOOD AND URINE, Plasma Clearance, , 4. Bilirubin, Bilirubin appears in urine (bilirubinuria) during hepatic, and posthepatic jaundice., 5. Urobilinogen, Normally, about 1 to 3.5 mg of urobilinogen is excreted, in urine daily. Excess of urobilinogen in urine indicates, hemolytic jaundice., , 6. Bile Salts, Presence of bile salts in urine reveals jaundice., 7. Blood, Presence of blood in urine (hematuria) indicates, glomerulonephritis, renal stones, infection or malignancy, of urinary tract. Hematuria must be confirmed by microscopic examination since chemical test fails to distinguish, the presence of red blood cells or hemoglobin in urine., , Plasma clearance is defined as the amount of plasma, that is cleared off a substance in a given unit of time., It is also known as renal clearance. It is based on Fick, principle., Determination of clearance value for certain, substances helps in assessing the following renal, functions:, 1. Glomerular filtration rate, 2. Renal plasma flow, 3. Renal blood flow., Value of following factors is required to determine, the plasma clearance of a particular substance:, 1. Volume of urine excreted, 2. Concentration of the substance in urine, 3. Concentration of the substance in blood., Formula to calculate clearance value, C =, , 8. Hemoglobin, Hemoglobin appears in urine (hemoglobinuria) during, excess hemolysis., 9. Nitrite, Presence of nitrite in urine indicates presence of bacteria, in urine since some bacteria convert nitrate into nitrite in, urine., , EXAMINATION OF BLOOD, 1. Estimation of Plasma Proteins, Normal values of plasma proteins:, Total proteins : 7.3 g/dL (6.4 to 8.3 g/dL), Serum albumin : 4.7 g/dL, Serum globulin : 2.3 g/dL, Fibrinogen, : 0.3 g/dL, Level of plasma proteins is altered during renal failure., 2. Estimation of Urea, Uric Acid and Creatinine, Normal values :, Urea, : 25 to 40 mg/dL, , Where, C, U, V, P, , =, =, =, =, , UV, P, Clearance, Concentration of the substance in urine, Volume of urine flow, Concentration of the substance in plasma., , 1. Measurement of Glomerular Filtration Rate, A substance that is completely filtered but neither, reabsorbed nor secreted should be used to measure, glomerular filtration rate (GFR). Inulin is the ideal, substance used to measure GFR. It is completely, filtered and neither reabsorbed nor secreted. So, inulin, clearance indicates GFR., Inulin clearance, A known amount of inulin is injected into the body. After, sometime, the concentration of inulin in plasma and, urine and the volume of urine excreted are estimated., For example,, Concentration of inulin in urine = 125 mg/dL, Concentration of inulin in plasma = 1 mg/dL, Volume of urine output, = 1 mL/min
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336 Section 5 t Renal Physiology and Skin, Thus,, UV, , Glomerular filtration rate =, , =, , 125 × 1, , P, = 125 mL/min, , 1, , Creatinine clearance is also used to measure GFR, accurately. It is easier than inulin clearance, because,, creatinine is already present in body fluids and its, plasma concentration is steady throughout the day. It, is completely filtered and being a metabolite it is neither, reabsorbed nor secreted. The normal value of GFR by, this method is approximately the same as determined, by inulin clearance., , 2. Measurement of Renal Plasma Flow, To measure renal plasma flow, a substance, which is, filtered and secreted but not reabsorbed, should be, used. Such a substance is paraaminohippuric acid, (PAH). PAH clearance indicates the amount of plasma, passed through kidneys., A known amount of PAH is injected into the body., After sometime, the concentration of PAH in plasma and, urine and the volume of urine excreted are estimated., For example,, Concentration of PAH in urine, = 66 mg/dL, Concentration of PAH in plasma = 0.1 mg/dL, Volume of urine output, = 1 mL/min, , i. Renal plasma flow, ii. Percentage of plasma volume in blood., i. Renal plasma flow, Renal plasma flow is measured by using PAH, clearance., ii. Percentage of plasma volume in blood, Percentage of plasma volume is indirectly determined, by using packed cell volume (PCV)., For example,, If PCV = 45%, Plasma volume in the blood = 100 – 45 = 55%, That is 55 mL of plasma is present in every 100 mL, of blood., Calculation of renal blood blow, Renal blood flow is calculated with the values of renal, plasma volume and percentage of plasma in blood by, using a formula given below., Renal blood flow =, , Renal plasma flow, % of plasma in blood, , For example,, Renal plasma flow = 660 mL/min, Amount of plasma in blood = 55%, Renal blood flow =, , 55/100, = 1,200 mL/min, , Thus,, Renal plasma flow =, , =, , UV, P, 66 × 1, 0.1, , = 660 mL/min, Diodrast clearance also can be used to measure, this., 3. Measurement of Renal Blood Flow, Values of factors necessary to determine renal blood, flow are:, , 660, , Urea Clearance Test, Urea clearance test is a clinical test to assess renal, function by using clearance of urea from plasma by, kidney every minute. This test requires a blood sample, to determine urea level in blood and two urine sample, collected at 1 hour interval to determine the urea cleared, by kidneys into urine. Normal value of urea clearance is, 70 mL/min., Urea is a waste product formed during protein, metabolism and excreted in urine. So, determination, of urea clearance forms a specific test to assess renal, function.
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Chapter, , Renal Failure, , 56, , INTRODUCTION, ACUTE RENAL FAILURE, , , , CAUSES, FEATURES, , CHRONIC RENAL FAILURE, , , , CAUSES, FEATURES, , INTRODUCTION, Renal failure refers to failure of excretory functions, of kidney. It is usually, characterized by decrease in, glomerular filtration rate (GFR). So GFR is considered, as the best index of renal failure. However, decrease, in GFR is not affected much during the initial stages of, renal failure. If 50% of the nephrons are affected, GFR, decreases only by 20% to 30%. It is because of the, compensatory mechanism by the unaffected nephrons., The renal failure may be either acute or chronic., Renal failure is always accompanied by other, complications such as:, 1. Deficiency of calcitriol (activated vitamin D) resulting, in reduction of calcium absorption from intestine, and hypocalcemia (Chapter 72). Deficiency of cal, citriol and hypocalcemia may cause secondary, hyperparathyroidism in some patients, 2. Deficiency of erythropoietin resulting in anemia, 3. Disturbances in acidbase balance., , ACUTE RENAL FAILURE, Acute renal failure is the abrupt or sudden stoppage, of renal functions. It is often reversible within few days, to few weeks. Acute renal failure may result in sudden, life-threatening reactions in the body with the need for, emergency treatment., , CAUSES, 1. Acute nephritis (inflammation of kidneys), which, usually develops by immune reaction, 2. Damage of renal tissues by poisons like lead,, mercury and carbon tetrachloride, 3. Renal ischemia, which develops during circulatory, shock, 4. Acute tubular necrosis (necrosis of tubular cells, in kidney) caused by burns, hemorrhage, snake, bite, toxins (like insecticides, heavy metals and, carbon tetrachloride) and drugs (like diuretics,, aminoglycosides and platinum derivatives), 5. Severe transfusion reactions, 6. Sudden fall in blood pressure during hemorrhage,, diarrhea, severe burns and cholera, 7. Blockage of ureter due to the formation of calculi, (renal stone) or tumor., FEATURES, 1. Oliguria (decreased urinary output), 2. Anuria (cessation of urine formation) in severe, cases, 3. Proteinuria (appearance of proteins in urine) includ, ing albuminuria (excretion of albumin in urine), 4. Hematuria (presence of blood in urine)
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338 Section 5 t Renal Physiology and Skin, 5. Edema due to increased volume of extracellular fluid, (ECF) caused by retention of sodium and water, 6. Hypertension within few days because of increased, ECF volume, 7. Acidosis due to the retention of metabolic end, products, 8. Coma due to severe acidosis (if the patient is not, treated in time) resulting in death within 10 to 14, days., , CHRONIC RENAL FAILURE, Chronic renal failure is the progressive, long standing, and irreversible impairment of renal functions., When some of the nephrons loose the function, the, unaffected nephrons can compensate it. However, when, more and more nephrons start losing the function over, the months or years, the compensatory mechanism fails, and chronic renal failure develops., CAUSES, 1., 2., 3., 4., 5., 6., 7., 8., , Chronic nephritis, Polycystic kidney disease, Renal calculi (kidney stones), Urethral constriction, Hypertension, Atherosclerosis, Tuberculosis, Slow poisoning by drugs or metals., , FEATURES, , of kidney to excrete the metabolic end products and, toxic substances., Common features of uremia, i., ii., iii., iv., v., vi., vii., viii., , Anorexia (loss of appetite), Lethargy, Drowsiness, Nausea and vomiting, Pigmentation of skin, Muscular twitching, tetany and convulsion, Confusion and mental deterioration, Coma., , 2. Acidosis, Uremia results in acidosis, which leads to coma and, death., 3. Edema, Failure of kidney to excrete sodium and electrolytes, causes increase in extracellular fluid volume resulting in, development of edema., 4. Blood Loss, Gastrointestinal bleeding accompanied by platelet, , dysfunction leads to heavy loss of blood., 5. Anemia, , Since, erythropoietin is not secreted in the kidney during, renal failure, the production of RBC decreases resulting, in normocytic normochromic anemia., , 1. Uremia, Uremia is the condition characterized by excess, accumulation of end products of protein metabolism, such as urea, nitrogen and creatinine in blood. There is, also accumulation of some toxic substances like organic, acids and phenols. Uremia occurs because of the failure, , 6. Hyperparathyroidism, Secondary hyperparathyroidism is developed due to the, deficiency of calcitriol (1,25dihydroxycholecalciferol). It, increases the removal of calcium from bones resulting, in osteomalacia.
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Chapter, , Micturition, , 57, , INTRODUCTION, FUNCTIONAL ANATOMY OF URINARY BLADDER AND URETHRA, , , , , URINARY BLADDER, URETHRA, URETHRAL SPHINCTERS, , NERVE SUPPLY TO URINARY BLADDER AND SPHINCTERS, , , , , SYMPATHETIC NERVE SUPPLY, PARASYMPATHETIC NERVE SUPPLY, SOMATIC NERVE SUPPLY, , FILLING OF URINARY BLADDER, , , , PROCESS OF FILLING, CYSTOMETROGRAM, , MICTURITION REFLEX, APPLIED PHYSIOLOGY – ABNORMALITIES OF MICTURITION, , , , , , ATONIC BLADDER – EFFECT OF DESTRUCTION OF SENSORY NERVE FIBERS, AUTOMATIC BLADDER, UNINHIBITED NEUROGENIC BLADDER, NOCTURNAL MICTURITION, , INTRODUCTION, Micturition is a process by which urine is voided from the, urinary bladder. It is a reflex process. However, in grown, up children and adults, it can be controlled voluntarily, to some extent. The functional anatomy and nerve, supply of urinary bladder are essential for the process, of micturition., , FUNCTIONAL ANATOMY OF URINARY, BLADDER AND URETHRA, URINARY BLADDER, Urinary bladder is a triangular hollow organ located in, lower abdomen. It consists of a body and neck. Wall of, the bladder is formed by smooth muscle. It consists of, three ill-defined layers of muscle fibers called detrusor, muscle, viz. the inner longitudinal layer, middle circular, layer and outer longitudinal layer. Inner surface of urinary, , bladder is lined by mucus membrane. In empty bladder,, the mucosa falls into many folds called rugae., At the posterior surface of the bladder wall, there is, a triangular area called trigone. At the upper angles of, this trigone, two ureters enter the bladder. Lower part of, the bladder is narrow and forms the neck. It opens into, urethra via internal urethral sphincter., URETHRA, Male urethra has both urinary function and reproductive, function. It carries urine and semen. Female urethra has, only urinary function and it carries only urine. So, male, urethra is structurally different from female urethra., Male Urethra, Male urethra is about 20 cm long. After origin from, bladder it traverses the prostate gland, which lies below, the bladder and then runs through the penis (Fig. 57.1).
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340 Section 5 t Renal Physiology and Skin, , FIGURE 57.1: Male urinary bladder and urethra, , Throughout its length, the urethra has mucus glands, called glands of Littre., Male urethra is divided into three parts:, 1. Prostatic urethra, 2. Membranous urethra, 3. Spongy urethra., 1. Prostatic urethra, Prostatic urethra is 3 cm long and it runs through, prostate gland. The prostatic fluid is emptied into this, part of urethra through prostatic sinuses. Sperms from, vas deferens and the fluid from seminal vesicles are, also emptied into prostatic urethra via ejaculatory ducts, (Chapter 74)., Part of the urethra after taking origin from neck of, bladder before entering the prostate gland is known as, preprostatic urethra. Its length is about 0.5 to 1.5 cm. This, part of urethra is considered as part of prostatic urethra., 2. Membranous urethra, Membranous urethra is about 1 to 2 cm long. It runs, from base of the prostate gland through urogenital, diaphragm up to the bulb of urethra., 3. Spongy urethra, Spongy urethra is also known as cavernous urethra and, its length is about 15 cm. Spongy urethra is surrounded, by corpus spongiosum of penis. It is divided into a, , proximal bulbar urethra and a distal penil urethra. Penile, urethra is narrow with a length of about 6 cm. It ends, with external urethral meatus or orifice, which is located, at the end of penis., The bilateral bulbourethral glands open into spongy, urethra. Bulbourethral glands are also called Cowper, glands., , Female Urethra, Female urethra is narrower and shorter than male, urethra. It is about 3.5 to 4 cm long. After origin from, bladder it traverses through urogenital diaphragm and, runs along anterior wall of vagina. Then it terminates, at external orifice of urethra, which is located between, clitoris and vaginal opening (Fig. 57.2)., URETHRAL SPHINCTERS, There are two urethral sphincters in urinary tract:, 1. Internal urethral sphincter, 2. External urethral sphincter., 1. Internal Urethral sphincter, This sphincter is situated between neck of the bladder, and upper end of urethra. It is made up of smooth muscle, fibers and formed by thickening of detrusor muscle. It, is innervated by autonomic nerve fibers. This sphincter, closes the urethra when bladder is emptied.
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Chapter 57 t Micturition 341, 2. External Urethral sphincter, , bladder and so, the sympathetic nerve is called nerve, , External sphincter is located in the urogenital diaphragm., This sphincter is made up of circular skeletal muscle, fibers, which are innervated by somatic nerve fibers., , NERVE SUPPLY TO URINARY, BLADDER AND SPHINCTERS, Urinary bladder and the internal sphincter are supplied, by sympathetic and parasympathetic divisions of auto, nomic nervous system where as, the external sphincter, is supplied by the somatic nerve fibers (Fig. 57.3)., , of filling., , PARASYMPATHETIC NERVE SUPPLY, Preganglionic fibers of parasympathetic nerve form, the pelvic nerve or nervus erigens. Pelvic nerve fibers, arise from second, third and fourth sacral segments, (S1, S2 and S3) of spinal cord. These fibers run through, hypogastric ganglion and synapse with postganglionic, neurons situated in close relation to urinary bladder and, internal sphincter (Table 57.1)., Function of Parasympathetic Nerve, , SYMPATHETIC NERVE SUPPLY, Preganglionic fibers of sympathetic nerve arise from, first two lumbar segments (L1 and L2) of spinal cord., After leaving spinal cord, the fibers pass through, lateral sympathetic chain without any synapse in the, sympathetic ganglia and finally terminate in hypogastric, ganglion. The postganglionic fibers arising from this, ganglion form the hypogastric nerve, which supplies, the detrusor muscle and internal sphincter., , Stimulation of parasympathetic (pelvic) nerve causes, contraction of detrusor muscle and relaxation of, the internal sphincter leading to emptying of urinary, bladder. So, parasympathetic nerve is called the nerve, of emptying or nerve of micturition., Pelvic nerve has also the sensory fibers, which carry, impulses from stretch receptors present on the wall of, the urinary bladder and urethra to the central nervous, system., , Function of Sympathetic Nerve, , SOMATIC NERVE SUPPLY, , The stimulation of sympathetic (hypogastric) nerve, causes relaxation of detrusor muscle and constriction, of the internal sphincter. It results in filling of urinary, , External sphincter is innervated by the somatic nerve, called pudendal nerve. It arises from second, third and, fourth sacral segments of the spinal cord., , FIGURE 57.2: Female urinary bladder and urethra, TABLE 57.1: Functions of nerves supplying urinary bladder and sphincters, Nerve, , On detrusor, muscle, , Sympathetic nerve, , Relaxation, , Parasympathetic nerve, Somatic nerve, , On internal, sphincter, , On external, sphincter, , Function, , Constriction, , Not supplied, , Filling of urinary bladder, , Contraction, , Relaxation, , Not supplied, , Emptying of urinary bladder, , Not supplied, , Not supplied, , Constriction, , Voluntary control of micturition
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342 Section 5 t Renal Physiology and Skin, A reasonable volume of urine can be stored in, urinary bladder without any discomfort and without much, increase in pressure inside the bladder (intravesical, pressure). It is due to the adaptation of detrusor muscle., This can be explained by cystometrogram., CYSTOMETROGRAM, Definition, Cystometry is the technique used to study the, relationship between intravesical pressure and volume, of urine in the bladder. Cystometrogram is the graphical, registration (recording) of pressure changes in urinary, bladder in relation to volume of urine collected in it., Method of Recording Cystometrogram, , Pudendal nerve maintains the tonic contraction of the, skeletal muscle fibers of the external sphincter and, keeps the external sphincter constricted always., During micturition, this nerve is inhibited. It causes, relaxation of external sphincter leading to voiding of, urine. Thus, the pudendal nerve is responsible for, voluntary control of micturition., , A doublelumen catheter is introduced into the urinary, bladder. One of the lumen is used to infuse fluid into the, bladder and the other one is used to record the pressure, changes by connecting it to a suitable recording, instrument., First, the bladder is emptied completely. Then, a, known quantity of fluid is introduced into the bladder at, regular intervals. The intravesical pressure developed, by the fluid is recorded continuously. A graph is obtained, by plotting all the values of volume and the pressure., This graph is the cystometrogram (Fig. 57.4)., , FILLING OF URINARY BLADDER, , Description of Cystometrogram, , FIGURE 57.3: Nerve supply to urinary bladder and urethra, , Function of Pudendal Nerve, , PROCESS OF FILLING, Urine is continuously formed by nephrons and it flows, into urinary bladder drop by drop through ureters. When, urine collects in the pelvis of ureter, the contraction sets, up in pelvis. This contraction is transmitted through rest, of the ureter in the form of peristaltic wave up to trigone, of the urinary bladder. Peristaltic wave usually travels at, a velocity of 3 cm/second. It develops at a frequency of, 1 to 5 per minute. The peristaltic wave moves the urine, into the bladder., After leaving the kidney, the direction of the ureter is, initially downward and outward. Then, it turns horizontally, before entering the bladder. At the entrance of ureters, into urinary bladder, a valvular arrangement is present., When peristaltic wave pushes the urine towards bladder,, this valve opens towards the bladder. The position of, ureter and the valvular arrangement at the end of ureter, prevent the back flow of urine from bladder into the, ureter when the detrusor muscle contracts. Thus, urine, is collected in bladder drop by drop., , Cystometrogram shows three segments., , FIGURE 57.4: Cystometrogram. Dotted lines indicate the, contraction of detrusor muscle.
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Chapter 57 t Micturition 343, Segment I, , MICTURITION REFLEX, , Initially, when the urinary bladder is empty, the intravesical, pressure is 0. When about 100 mL of fluid is collected,, the pressure rises sharply to about 10 cm H2O., , Micturition reflex is the reflex by which micturition, occurs. This reflex is elicited by the stimulation of stretch, receptors situated on the wall of urinary bladder and, urethra. When about 300 to 400 mL of urine is collected, in the bladder, intravesical pressure increases. This, stretches the wall of bladder resulting in stimulation of, stretch receptors and generation of sensory impulses., , Segment II, Segment II shows the plateau, i.e. no change in intra, vesical pressure. It remains at 10 cm H2O even after, introducing 300 to 400 mL of fluid. It is because of, adaptation of urinary bladder by relaxation. It is in, accordance with law of Laplace., Law of Laplace, According to this law, the pressure in a spherical organ, is inversely proportional to its radius, the tone remaining, constant. That is, if radius is more, the pressure is less, and if radius is less the pressure is more, provided the, tone remains constant., P =, , T, , R, Where, P = Pressure, T = Tension, R = Radius, Accordingly in the bladder, the tension increases, as the urine is filled. At the same time, the radius also, increases due to relaxation of detrusor muscle. Because, of this, the pressure does not change and plateau, appears in the graph., With 100 mL of urine and 10 cm H2O of intravesical, pressure, the desire for micturition occurs. Desire for, micturition is associated with a vague feeling in the, perineum. But it can be controlled voluntarily., An additional volume of about 200 to 300 mL of, urine can be collected in bladder without much increase, in pressure. However, when total volume rises beyond, 400 mL, the pressure starts rising sharply., Segment III, As the pressure increases with collection of 300 to 400, mL of fluid, the contraction of detrusor muscle becomes, intense, increasing the consciousness and the urge, for micturition. Still, voluntary control is possible up to, volume of 600 to 700 mL at which the pressure rises to, about 35 to 40 cm H2O., When the intravesical pressure rises above 40 cm, water, the contraction of detrusor muscle becomes still, more intense. And, voluntary control of micturition is not, possible. Now, pain sensation develops and micturition, is a must at this stage., , Pathway for Micturition Reflex, Sensory (afferent) impulses from the receptors reach, the sacral segments of spinal cord via the sensory fibers, of pelvic (parasympathetic) nerve. Motor (efferent), impulses produced in spinal cord, travel through motor, fibers of pelvic nerve towards bladder and internal, sphincter. Motor impulses cause contraction of detrusor, muscle and relaxation of internal sphincter so that, urine, enters the urethra from the bladder (Fig. 57.5)., Once urine enters urethra, the stretch receptors in, the urethra are stimulated and send afferent impulses, to spinal cord via pelvic nerve fibers. Now the impulses, generated from spinal centers inhibit pudendal nerve., So, the external sphincter relaxes and micturition, occurs., Once a micturition reflex begins, it is self-regenerative, i.e. the initial contraction of bladder further, activates the receptors to cause still further increase, in sensory impulses from the bladder and urethra., These impulses, in turn cause further increase in reflex, contraction of bladder. The cycle continues repeatedly, until the force of contraction of bladder reaches the, maximum and the urine is voided out completely., During micturition, the flow of urine is facilitated, by the increase in the abdominal pressure due to the, voluntary contraction of abdominal muscles., Higher Centers for Micturition, Spinal centers for micturition are present in sacral, and lumbar segments. But, these spinal centers are, regulated by higher centers. The higher centers, which, control micturition are of two types, inhibitory centers, and facilitatory centers., Inhibitory centers for micturition, Centers in midbrain and cerebral cortex inhibit the, micturition by suppressing spinal micturition centers., Facilitatory centers for micturition, Centers in pons facilitate micturition via spinal, centers. Some centers in cerebral cortex also facilitate, micturition.
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344 Section 5 t Renal Physiology and Skin, loses the tone and becomes flaccid. So the bladder is, completely filled with urine without any micturition., Now, urine overflows in drops as and when it, enters the bladder. It is called overflow incontinence or, overflow dribbling., , Conditions of Destruction of Sensory Nerve Fibers, 1. Spinal injury: During the first stage (stage of spinal, shock) after injury to sacral segments of spinal cord, (Chapter 143) the bladder becomes atonic, 2. Syphilis: Syphilis results in the degenerative nervous, disorder called tabes dorsalis, which is characterized, by the degeneration of dorsal (sensory) nerve roots, (Chapter 143). Degeneration of sensory nerve roots, of sacral region develops atonic bladder. The atonic, bladder in tabes dorsalis is called tabetic bladder., AUTOMATIC BLADDER, , FIGURE 57.5: Micturition reflex, , APPLIED PHYSIOLOGY –, ABNORMALITIES OF MICTURITION, ATONIC BLADDER – EFFECT OF, DESTRUCTION OF SENSORY NERVE FIBERS, Atonic bladder is the urinary bladder with loss of tone, in detrusor muscle. It is also called flaccid neurogenic, bladder or hypoactive neurogenic bladder. It is caused, by destruction of sensory (pelvic) nerve fibers of urinary, bladder., Due to the destruction of sensory nerve fibers, the, bladder is filled without any stretch signals to spinal cord., Due to the absence of stretch signals, detrusor muscle, , Automatic bladder is the urinary bladder characterized, by hyperactive micturition reflex with loss of voluntary, control. So, even a small amount of urine collected, in the bladder elicits the micturition reflex resulting in, emptying of bladder., This occurs during the second stage (stage of, recovery) after complete transection of spinal cord, above the sacral segments., During the first stage (stage of spinal shock) after, complete transection of spinal cord above sacral, segments, the urinary bladder loses the tone and, becomes atonic resulting in overflow incontinence., During the second stage after shock period, the, micturition reflex returns. However, the voluntary control, is lacking because of absence of inhibition or facilitation, of micturition by higher centers. There is hypertrophy of, detrusor muscles so that the capacity of bladder reduces., Some patients develop hyperactive micturition reflex., UNINHIBITED NEUROGENIC BLADDER, Uninhibited neurogenic bladder is the urinary bladder, with frequent and uncontrollable micturition caused by, lesion in midbrain. It is also called spastic neurogenic, bladder or hyperactive neurogenic bladder., The lesion in midbrain causes continuous excitation, of spinal micturition centers resulting in frequent and, uncontrollable micturition. Even a small quantity of urine, collected in bladder will elicit the micturition reflex., NOCTURNAL MICTURITION, Nocturnal micturition is the involuntary voiding of urine, during night. It is otherwise known as enuresis or
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Chapter 57 t Micturition 345, bedwetting. It occurs due to the absence of voluntary, , control of micturition. It is a common and normal process, in infants and children below 3 years. It is because of, incomplete myelination of motor nerve fibers of the, bladder. When myelination is complete, voluntary control, of micturition develops and bedwetting stops., , If nocturnal micturition occurs after 3 years of age, it is considered abnormal. It occurs due to neurological, disorders like lumbosacral vertebral defects. It can also, occur due to psychological factors. Loss of voluntary, control of micturition occurs even during the impairment, of motor area of cerebral cortex.
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Chapter, , Dialysis and, Artificial Kidney, , 58, , DIALYSIS, ARTIFICIAL KIDNEY, , , , , , , , , MECHANISM OF FUNCTION OF ARTIFICIAL KIDNEY, , FREQUENCY AND DURATION OF DIALYSIS, DIALYSATE, PERITONEAL DIALYSIS, UREMIA, COMPLICATIONS OF DIALYSIS, , DIALYSIS, Dialysis is the procedure to remove waste materials, and toxic substances and to restore normal volume and, composition of body fluid in severe renal failure. It is, also called hemodialysis., , ARTIFICIAL KIDNEY, Artificial kidney is the machine that is used to carry, out dialysis during renal failure. It is used to treat the, patients suffering from:, 1. Acute renal failure, 2. Chronic or permanent renal failure., MECHANISM OF FUNCTION, OF ARTIFICIAL KIDNEY, The term dialysis refers to diffusion of solutes from, an area of higher concentration to the area of lower, concentration, through a semipermeable membrane., This forms the principle of artificial kidney., Patient’s arterial blood is passed continuously, or intermittently through the artificial kidney and then, back to the body through the vein. Heparin is used as, an anticoagulant while passing the blood through the, machine., Inside the artificial kidney, the blood passes through a, dialyzer called hemofilter, which contains minute channels, , interposed between two cellophane membranes (Fig., 58.1). The cellophane membranes are porous in nature., The outer surface of these membranes is bathed in the, dialyzing fluid called dialysate. The used dialysate in the, artificial kidney is constantly replaced by fresh dialysate., Urea, creatinine, phosphate and other unwanted, substances from the blood pass into the dialysate by, concentration gradient. The essential substances, required by the body diffuse from dialysate into blood., Almost all the substances, except plasma proteins are, exchanged between the blood and dialysate through, the cellophane membranes., In addition to the dialyzer, the dialysis machine has, several blood pumps with pressure monitors, which, enable easy flow of blood from the patient to the machine, and back to the patient. It also has pumps for flow of, fresh dialysate and for drainage of used dialysate., Total amount of blood in the dialysis machine at a, time is about 500 mL. The rate of blood flow through the, dialysis machine is about 200 to 300 mL/minute. The, rate of dialysate flow is about 500 mL/minute., , FREQUENCY AND DURATION OF DIALYSIS, The frequency and duration of dialysis depends upon, the severity of renal dysfunction. Dialysis is done usually, thrice a week in severe uremia. Each time, the artificial, kidney is used for about 6 hours.
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Chapter 58 t Dialysis and Artificial Kidney 347, , FIGURE 58.1: Principle of dialysis, , DIALYSATE, The concentration of various substances in the dialysate, is adjusted in accordance with the needs of the patient’s, body. The fluid does not contain urea, urate, sulfate,, phosphate or creatinine, so that, these substances, move from the blood to the dialysate., The fluid has low concentration of sodium, potassium, and chloride ions than in the uremic blood. But the, concentration of glucose, bicarbonate and calcium ions, is more in the dialysate than in the uremic blood., , PERITONEAL DIALYSIS, Peritoneal dialysis is the technique in which peritoneal, membrane is used as a semipermeable membrane. It, is also used to treat the patients suffering from renal, failure., A catheter is inserted into the peritoneal cavity through, anterior abdominal wall and sutured. The dialysate is, passed through this catheter under gravity. The required, electrolytes from dialysate pass through vascular perito, neum into blood vessels of abdominal cavity. Urea,, creatinine, phosphate and other unwanted substances, diffuse from blood vessels into dialysate. Later, dialysate, is drained from peritoneal cavity by gravity., Peritoneal dialysis is a simple, convenient and, lessexpensive technique, compared to hemodialysis., , Patients themselves can change the fluid on an, outpatient basis. However, it has few drawbacks. It is, less efficient in removing some of the toxic substances, and it may lead to complications by infections., , UREMIA, Uremia is explained in Chapter 56. Blood level of urea,, nitrogen and creatinine increases during uremia. Toxic, substances such as organic acids and phenols also, accumulate in blood., Artificial kidney can excrete more than double the, amount of urea that could be excreted by both the, normal kidneys. About 200 to 250 mL of plasma could be, cleared off urea per minute by the artificial kidney. But,, the urea clearance by normal kidney is only about 70, mL/minute. Refer Chapter 55 for urea clearance test., , COMPLICATIONS OF DIALYSIS, Complications of dialysis depend upon the patient’s, condition, age, existence of diseases other than renal, failure and many other factors., Common complications of dialysis in individuals, having only renal dysfunction are:, 1. Sleep disorders, 2. Anxiety, 3. Depression.
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Chapter, , Diuretics, , , , , , 59, , INTRODUCTION, GENERAL USES OF DIURETICS, ABUSES AND COMPLICATIONS OF DIURETICS, TYPES OF DIURETICS, , , , , , , , , OSMOTIC DIURETICS, DIURETICS WHICH INHIBIT ACTIVE REABSORPTION OF ELECTROLYTES, DIURETICS WHICH INHIBIT ACTION OF ALDOSTERONE, DIURETICS WHICH INHIBIT ACTIVITY OF CARBONIC ANHYDRASE, DIURETICS WHICH INCREASE GLOMERULAR FILTRATION RATE, DIURETICS WHICH INHIBIT SECRETION OF ADH, DIURETICS WHICH INHIBIT ADH RECEPTORS, , INTRODUCTION, Diuretics or diuretic agents are the substances, which enhance the urine formation and output. These, substances increase the excretion of water, sodium and, chloride through urine. Diuretic agents increase the urine, formation, by influencing any of the processes involved, in urine formation. Diuretics are commonly called ‘water, pills’., , GENERAL USES OF DIURETICS, Diuretics are generally used for the treatment of disorders, involving increase in extracellular fluid volume like:, 1. Hypertension, 2. Congestive cardiac failure, 3. Edema., Diuretic agents prevent hypertension, congestive, cardiac failure and edema, by increasing the urinary, output and reducing extracellular fluid (ECF) volume., , ABUSES AND COMPLICATIONS, OF DIURETICS, Nowadays, diuretics are misused in order to reduce, the body weight and keep the body slim. Even persons, , suffering from eating disorders attempt to reduce body, weight by misusing the diuretics., However, prolonged use of these substances leads, to complications like syndrome of diuretic-dependent, sodium retention, characterized by edema. The adverse, effects depend upon the type of diuretic agents used., Adverse Effects of Diuretics, 1., 2., 3., 4., 5., 6., 7., 8., , Dehydration, Electrolyte imbalance, Potassium deficiency, Headache, Dizziness, Renal damage, Cardiac arrhythmia, Heart palpitations., , TYPES OF DIURETICS, Diuretics are classified into seven types:, 1. Osmotic diuretics, 2. Diuretics which inhibit active reabsorption of electro, lytes, 3. Diuretics which inhibit action of aldosterone
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Chapter 59 t Diuretics 349, 4. Diuretics which inhibit activity of carbonic, anhydrase, 5. Diuretics which increase glomerular filtration rate, 6. Diuretics which inhibit secretion of ADH, 7. Diuretics which inhibit ADH receptors., OSMOTIC DIURETICS, Osmotic diuretics are the substances that induce osmotic, diuresis. Osmotic diuresis is the type of diuresis that, occurs because of increased osmotic pressure. Some, of the osmotically active substances are not reabsorbed, from renal tubules. When injected in large quantities, into the body, these substances increase the osmotic, pressure in the tubular fluid. Increased osmotic pressure, in the tubular fluid, in turn reduces water reabsorption. It, leads to excretion of excess of water through urine., Elevated blood sugar level in diabetes can also, cause osmotic diuresis in the same manner., Examples, i., ii., iii., iv., , Urea, Mannitol, Sucrose, Glucose., , DIURETICS WHICH INHIBIT ACTIVE, REABSORPTION OF ELECTROLYTES, Diuretics of this type inhibits the active reabsorption, of electrolytes like sodium and potassium from the, renal tubular fluid. Inhibition of electrolyte reabsorption, causes osmotic diuresis. These diuretic agents are of, three types:, 1. Loop Diuretics – Diuretics which Inhibit, the Electrolyte Reabsorption in Thick, Ascending Limb of Henle Loop, Loop diuretics are the substances that inhibit electrolyte, reabsorption in Henle loop. These diuretics inhibit the, sodium and chloride reabsorption from thick ascending, limb of Henle loop. So, the osmotic pressure in tubular, fluid increases, leading to diuresis. The osmolarity of, medullary interstitial fluid also decreases due to inhibition, of sodium reabsorption into medullary interstitium. So,, the medullary interstitium fails to concentrate the urine,, resulting in loss of excess fluid through urine., Examples, i. Furosemide, ii. Torasemide, iii. Bumetanide., , 2. Diuretics which Inhibit Active, Transport of Electrolytes In Proximal, Part of Distal Convoluted Tubule, Diuretics of this type inhibit sodium reabsorption in proximal, part of the distal convoluted tubules. These diuretics are, usually called thiazide and related diuretics., Examples, i. Chlorothiazide, ii. Metolazone, iii. Chlortalidone., 3. Diuretics which Inhibit Active Transport, of Electrolytes in Distal Part of Distal, Convoluted Tubule and Collecting Duct, Some of the diuretics inhibit reabsorption of sodium, and excretion of potassium in distal portion of the distal, convoluted tubule and collecting duct. Such substances, are called potassium-retaining diuretics or potassiumsparing diuretics., , Examples, i. Triamterene, ii. Amiloride., DIURETICS WHICH INHIBIT, ACTION OF ALDOSTERONE, Some diuretics inhibit sodium reabsorption and, potassium excretion in the distal convoluted tubule and, collecting duct, by inhibiting the action of aldosterone., These substances are also called the potassium, retaining diuretics or aldosterone antagonists., Examples, i. Spironolactone, ii. Eperenone., DIURETICS WHICH INHIBIT ACTIVITY, OF CARBONIC ANHYDRASE, Some diuretics inhibit the activity of carbonic anhydrase, in proximal convoluted tubules and prevent reabsorption, of bicarbonates from renal tubules, resulting in osmotic, diuresis. Such diuretic agents are called carbonic, anhydrase inhibitors. Acetazolamide is a carbonic, anhydrase inhibitor., DIURETICS WHICH INCREASE GLOMERULAR, FILTRATION RATE, Some xanthines (alkaloids, used as mild stimulants) cause, diuresis by increasing the glomerular filtration rate and to, some extent by decreasing the sodium reabsorption.
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350 Section 5 t Renal Physiology and Skin, Examples, i. Caffeine, ii. Theophylline., DIURETICS WHICH INHIBIT, SECRETION OF ANTIDIURETIC HORMONE, Some diuretics produce diuresis by inhibiting the, secretion of ADH., , Examples, i. Water, ii. Ethanol., DIURETICS WHICH INHIBIT ANTIDIURETIC, HORMONE RECEPTORS, The antagonists of V2 receptors cause diuresis by, inhibiting the receptors of antidiuretic hormone, thereby, preventing the activity of this hormone.
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Chapter, , Structure of Skin, , 60, , INTRODUCTION, , , LAYERS OF SKIN, , EPIDERMIS, , , , , , , STRATUM CORNEUM, STRATUM LUCIDUM, STRATUM GRANULOSUM, STRATUM SPINOSUM, STRATUM GERMINATIVUM, , DERMIS, , , , SUPERFICIAL PAPILLARY LAYER, RETICULAR LAYER, , APPENDAGES OF SKIN, COLOR OF SKIN, , , , PIGMENTATION OF SKIN, HEMOGLOBIN IN THE BLOOD, , INTRODUCTION, Skin is the largest organ of the body. It is not uniformly, thick. At some places it is thick and at some places it is, thin. The average thickness of the skin is about 1 to 2, mm. In the sole of the foot, palm of the hand and in the, interscapular region, it is considerably thick, measuring, about 5 mm. In other areas of the body, the skin is thin., It is thinnest over eyelids and penis, measuring about, 0.5 mm only., LAYERS OF SKIN, Skin is made up of two layers:, I. Outer epidermis, II. Inner dermis., , EPIDERMIS, Epidermis is the outer layer of skin. It is formed by, stratified epithelium. Important feature of epidermis, is that, it does not have blood vessels (Fig. 60.1)., , Nutrition is provided to the epidermis by the capillaries, of dermis., Layers of Epidermis, Epidermis is formed by five layers:, 1. Stratum corneum, 2. Stratum lucidum, 3. Stratum granulosum, 4. Stratum spinosum, 5. Stratum germinativum., 1. STRATUM CORNEUM, Stratum corneum is also known as horny layer. It is the, outermost layer and consists of dead cells, which are, called corneocytes. These cells lose their nucleus due to, pressure and become dead cells. The cytoplasm is flat, tened with fibrous protein known as keratin. Apart from, this, these cells also contain phospholipids and glycogen.
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352 Section 5 t Renal Physiology and Skin, , FIGURE 60.1: Structure of skin, , 2. STRATUM LUCIDUM, , 5. STRATUM GERMINATIVUM, , Stratum lucidum is made up of flattened epithelial cells., Many cells have degenerated nucleus and in some, cells, the nucleus is absent. As these cells exhibit, shiny character, the layer looks like a homogeneous, translucent zone. So, this layer is called stratum lucidum, (lucid = clear)., , Stratum germinativum is a thick layer made up of, polygonal cells, superficially and columnar or cuboidal, epithelial cells in the deeper parts. Here, new cells are, constantly formed by mitotic division. The newly formed, cells move continuously towards the stratum corneum., The stem cells, which give rise to new cells, are known, as keratinocytes., Another type of cells called melanocytes are, scattered between the keratinocytes. Melanocytes, produce the pigment called melanin. The color of the, skin depends upon melanin., From this layer, some projections called rete ridges, extend down up to dermis. These projections provide, anchoring and nutritional function., , 3. STRATUM GRANULOSUM, Stratum granulosum is a thin layer with two to five, rows of flattened rhomboid cells. Cytoplasm contains, granules of a protein called keratohyalin. Keratohyalin, is the precursor of keratin., 4. STRATUM SPINOSUM, Stratum spinosum is also known as prickle cell layer, because, the cells of this layer possess some spinelike, protoplasmic projections. By these projections, the cells, are connected to one another., , DERMIS, Dermis is the inner layer of the skin. It is a connective, tissue layer, made up of dense and stout collagen fibers,
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Chapter 60 t Structure of Skin 353, fibroblasts and histiocytes. Collagen fibers exhibit elastic, property and are capable of storing or holding water., Collagen fibers contain the enzyme collagenase, which, is responsible for wound healing., , Hair follicles with hair, nails, sweat glands, sebaceous, glands and mammary glands are considered as append, ages of the skin., , Layers of Dermis, , COLOR OF SKIN, , Dermis is made up of two layers:, 1. Superficial papillary layer, 2. Deeper reticular layer., , Color of skin depends upon two important factors:, 1. Pigmentation of skin, 2. Hemoglobin in the blood., , SUPERFICIAL PAPILLARY LAYER, , PIGMENTATION OF SKIN, , Superficial papillary layer projects into the epidermis., It contains blood vessels, lymphatics and nerve fibers., This layer also has some pigmentcontaining cells, known as chromatophores., Dermal papillae are fingerlike projections, arising, from the superficial papillary dermis. Each papilla, contains a plexus of capillaries and lymphatics, which, are oriented perpendicular to the skin surface. The, papillae are surrounded by rete ridges, extending from, the epidermis., , Cells of the skin contain a brown pigment called melanin,, which is responsible for the color of the skin. It is synthe, sized by melanocytes, which are present mainly in, the stratum germinativum and stratum spinosum of, epidermis. After synthesis, this pigment spreads to the, cells of the other layers., , RETICULAR LAYER, Reticular layer is made up of reticular and elastic fibers., These fibers are found around the hair bulbs, sweat, glands and sebaceous glands. The reticular layer, also contains mast cells, nerve endings, lymphatics,, epidermal appendages and fibroblasts., Immediately below the dermis, subcutaneous tissue, is present. It is a loose connective tissue, which connects, the skin with the internal structures of the body. It serves, as an insulator to protect the body from excessive heat, and cold of the environment. Lot of smooth muscles, called arrector pili are also found in skin around the hair, follicles., , APPENDAGES OF SKIN, , Melanin, Melanin is the skin pigment and it forms the major, color determinant of human skin. Skin becomes dark, when melanin content increases. It is protein in nature, and it is synthesized from the amino acid tyrosine via, dihydroxyphenylalanine (DOPA)., Deficiency of melanin leads to albinism (hypopig, mentary congenital disorder)., HEMOGLOBIN IN THE BLOOD, Amount and nature of hemoglobin that circulates in the, cutaneous blood vessels play an important role in the, coloration of the skin., Skin becomes:, i. Pale, when hemoglobin content decreases, ii. Pink, when blood rushes to skin due to cutaneous, vasodilatation (blushing), iii. Bluish during cyanosis, which is caused by, excess amount of reduced hemoglobin.
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Chapter, , Functions of Skin, , 61, , FUNCTIONS OF SKIN, , , , , , , , , , , PROTECTIVE FUNCTION, SENSORY FUNCTION, STORAGE FUNCTION, SYNTHETIC FUNCTION, REGULATION OF BODY TEMPERATURE, REGULATION OF WATER AND ELECTROLYTE BALANCE, EXCRETORY FUNCTION, ABSORPTIVE FUNCTION, SECRETORY FUNCTION, , FUNCTIONS OF SKIN, Primary function of skin is protection of organs. However,, it has many other important functions also., 1. PROTECTIVE FUNCTION, Skin forms the covering of all the organs of the body and, protects these organs from the following factors:, i. Bacteria and toxic substances, ii. Mechanical blow, iii. Ultraviolet rays., , inflammation, immunological reactions, tissue repair, and wound healing, b. Antimicrobial peptides like β-defensins, which, prevent invasion of microbes., ii. Protection from Mechanical Blow, Skin is not tightly placed over the underlying organs, or tissues. It is somewhat loose and moves over the, underlying subcutaneous tissues. So, the mechanical, impact of any blow to the skin is not transmitted to the, underlying tissues., , i. Protection from Bacteria and Toxic Substances, Skin covers the organs of the body and protects, the organs from having direct contact with external, environment. Thus, it prevents the bacterial infection., Lysozyme secreted in skin destroys the bacteria., Keratinized stratum corneum of epidermis is responsible, for the protective function of skin. This layer also offers, resistance against toxic chemicals like acids and alkalis., If the skin is injured, infection occurs due to invasion of, bacteria from external environment., During injury or skin infection, the keratinocytes, secrete:, a. Cytokines like interleukins, α-tumor necrosis, factor and γ-interferon, which play important role in, , iii. Protection from Ultraviolet Rays, Skin protects the body from ultraviolet rays of sunlight., Exposure to sunlight or to any other source of ultraviolet, rays increases the production of melanin pigment in, skin. Melanin absorbs ultraviolet rays. At the same time,, the thickness of stratum corneum increases. This layer, of epidermis also absorbs the ultraviolet rays., 2. SENSORY FUNCTION, Skin is considered as the largest sense organ in the, body. It has many nerve endings, which form the, specialized cutaneous receptors (Chapter 139).
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Chapter 61 t Functions of Skin 355, These receptors are stimulated by sensations of, touch, pain, pressure or temperature sensation and, convey these sensations to the brain via afferent nerves., At the brain level, perception of different sensations, occurs., , of sebum prevents loss of heat from the body in cold, environment. More details are given in Chapter 63., 6. REGULATION OF WATER AND, ELECTROLYTE BALANCE, , 3. STORAGE FUNCTION, , Skin regulates water balance and electrolyte balance by, excreting water and salts through sweat., , Skin stores fat, water, chloride and sugar. It can also, store blood by the dilatation of the cutaneous blood, vessels., , 7. EXCRETORY FUNCTION, , 4. SYNTHETIC FUNCTION, Vitamin D3 is synthesized in skin by the action of, ultraviolet rays from sunlight on cholesterol., 5. REGULATION OF BODY TEMPERATURE, Skin plays an important role in the regulation of, body temperature. Excess heat is lost from the body, through skin by radiation, conduction, convection and, evaporation. Sweat glands of the skin play an active, part in heat loss, by secreting sweat. The lipid content, , Skin excretes small quantities of waste materials like, urea, salts and fatty substance., 8. ABSORPTIVE FUNCTION, Skin absorbs, ointments., , fat-soluble, , substances, , and, , some, , 9. SECRETORY FUNCTION, Skin secretes sweat through sweat glands and sebum, through sebaceous glands. By secreting sweat, skin, regulates body temperature and water balance. Sebum, keeps the skin smooth and moist.
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Chapter, , Glands of Skin, , 62, , GLANDS OF SKIN, SEBACEOUS GLANDS, SWEAT GLANDS, , , , ECCRINE GLANDS, APOCRINE GLANDS, , GLANDS OF SKIN, Skin contains two types of glands, namely sebaceous, glands and sweat glands., , SEBACEOUS GLANDS, Sebaceous glands are simple or branched alveolar, glands, situated in the dermis of skin., Structure, Sebaceous glands are ovoid or spherical in shape and, are situated at the side of the hair follicle. These glands, develop from hair follicles. So, the sebaceous glands, are absent over the thick skin, which is devoid of hair, follicles. Each gland is covered by a connective tissue, capsule. The alveoli of the gland are lined by stratified, epithelial cells., Sebaceous glands open into the neck of the hair, follicle through a duct. In some areas like face, lips,, nipple, glans penis and labia minora, the sebaceous, glands open directly into the exterior., Secretion of Sebaceous Gland – Sebum, Sebaceous glands secrete an oily substance called, sebum. Sebum is formed by the liquefaction of the, alveolar cells and poured out through the ducts either, via the hair follicle or directly into the exterior., Composition of Sebum, Sebum contains:, 1. Free fatty acids, , 2., 3., 4., 5., 6., , Triglycerides, Squalene, Sterols, Waxes, Paraffin., , Functions of Sebum, 1. Free fatty acid content of the sebum has antibacterial, and antifungal actions. Thus, it prevents the infection, of skin by bacteria or fungi, 2. Lipid nature of sebum keeps the skin smooth and oily., It protects the skin from unnecessary desquamation, and injury caused by dryness, 3. Lipids of the sebum prevent heat loss from the body., It is particularly useful in cold climate., Activation of Sebaceous Glands at Puberty, Sebaceous glands are inactive till puberty. At the time of, puberty, these glands are activated by sex hormones in, both males and females., At the time of puberty, particularly in males, due to, the increased secretion of sex hormones, especially, dehydroepiandrosterone, the sebaceous glands are, stimulated suddenly. It leads to the development of acne, on the face., Acne, Acne is the localized inflammatory condition of the skin,, characterized by pimples on face, chest and back. It, occurs because of overactivity of sebaceous glands., Acne vulgaris is the common type of acne that is
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Chapter 62 t Glands of Skin 357, developed during adolescence. Acne disappears within, few years, when the sebaceous glands become adapted, to the sex hormones., , SWEAT GLANDS, Sweat glands are of two types:, 1. Eccrine glands, 2. Apocrine glands., , secretion increases during increase in temperature and, emotional conditions., Eccrine glands play an important role in regulating, the body temperature by secreting sweat. Sweat, contains water, sodium chloride, urea and lactic acid., Control of Eccrine Glands, Eccrine glands are under nervous control and are, supplied by sympathetic postganglionic cholinergic, nerve fibers, which secrete acetylcholine. Stimulation of, these nerves causes secretion of sweat., , ECCRINE GLANDS, Distribution, Eccrine glands are distributed throughout the body (Table, 62.1). There are many eccrine glands over thick skin., Structure, Eccrine sweat gland is a tubular coiled gland., It consists of two parts:, 1. A coiled portion lying deeper in dermis, which, secretes the sweat, 2. A duct portion, which passes through dermis and, epidermis., Eccrine sweat gland opens out through the sweat, pore. The coiled portion is formed by single layer, of columnar or cuboidal epithelial cells, which are, secretory in nature. Epithelial cells are interposed by, the myoepithelial cells. Myoepithelial cells support the, secretory epithelial cells., The duct of eccrine gland is formed by two layers of, cuboidal epithelial cells., Secretory Activity of Eccrine Glands, Eccrine glands function throughout the life since birth., These glands secrete a clear watery sweat. The, , APOCRINE GLANDS, Distribution, Apocrine glands are situated only in certain areas of the, body like axilla, pubis, areola and umbilicus., Structure, Apocrine glands are also tubular coiled glands. The, coiled portion lies in deep dermis. But, the duct opens, into the hair follicle above the opening of sebaceous, gland., Secretory Activity of Apocrine Glands, Apocrine sweat glands are nonfunctional till puberty and, start functioning only at the time of puberty. In old age,, the function of these glands gradually declines., The secretion of the apocrine glands is thick and, milky. At the time of secretion, it is odorless. When, microorganisms grow in this secretion, a characteristic, odor develops in the regions where apocrine glands, are present. Secretion increases only in emotional, conditions., , TABLE 62.1: Differences between eccrine and apocrine sweat glands, Features, , Eccrine glands, , Apocrine glands, , 1. Distribution, , Throughout the body, , Only in limited areas like axilla, pubis, areola, and umbilicus, , 2. Opening, , Exterior through sweat pore, , Into the hair follicle, , 3. Period of functioning, , Function throughout life, , Start functioning only at puberty, , 4. Secretion, , Clear and watery, , Thick and milky, , 5. Regulation of body, temperature, , Play important role in temperature, regulation, , Do not play any role in temperature, regulation, , 6. Conditions when secretion, increases, , During increased temperature and, emotional conditions, , Only during emotional conditions, , 7. Control of secretory activity, , Under nervous control, , Under hormonal control, , 8. Nerve supply, , Sympathetic cholinergic fibers, , Sympathetic adrenergic fibers
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358 Section 5 t Renal Physiology and Skin, Apocrine glands do not play any role in temperature, regulation like eccrine glands., Control of Apocrine Glands, Apocrine glands are innervated by sympathetic, adrenergic nerve fibers. But, the secretory activity is, not under nervous control. However, adrenaline from, adrenal medulla causes secretion by apocrine glands., Glands of eyelids, glands of external auditory, meatus and mammary glands are the modified apocrine, glands., Pheromones, Pheromones are a group of chemical substances that, are secreted by apocrine glands. Some scientists call, this substance as vomeropherins. When secreted into, environment by an organism, pheromones produce, some behavioral or physiological changes in other, , members of the same species. Pheromones are mostly, present in urine, vaginal fluid and other secretions of, mammals and influence the behavior and reproductive, cycle in these animals., Details of pheromones in lower animals are well, documented. However, human pheromones are not, fully studied., Recently, it is found that the pheromones excreted, in axilla of a woman affects the menstrual cycle of, her room-mate or other woman living with her. These, substances stimulate receptors of vomeronasal, receptors. Vomeronasal receptors are distinct from, other olfactory receptors and detect specially the odor, of pheromones. Impulses from these receptors are, transmitted to hypothalamus, which influences the, menstrual cycle via pituitary gonadal axis. This effect of, pheromones on the menstrual cycle of other individuals, is called dormitory effect. Refer Chapter 177 for details, of vomeronasal organ and its receptors.
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Body Temperature, , Chapter, , 63, , INTRODUCTION, , , , HOMEOTHERMIC ANIMALS, POIKILOTHERMIC ANIMALS, , BODY TEMPERATURE, , , , , NORMAL BODY TEMPERATURE, TEMPERATURE AT DIFFERENT PARTS OF THE BODY, VARIATIONS OF BODY TEMPERATURE, , HEAT BALANCE, , , , HEAT GAIN OR HEAT PRODUCTION IN THE BODY, HEAT LOSS FROM THE BODY, , REGULATION OF BODY TEMPERATURE, , , , , HEAT LOSS CENTER, HEAT GAIN CENTER, MECHANISM OF TEMPERATURE REGULATION, , APPLIED PHYSIOLOGY, , , , HYPERTHERMIA – FEVER, HYPOTHERMIA, , INTRODUCTION, , BODY TEMPERATURE, , Living organisms are classified into two groups, depending, upon the maintenance (regulation) of body temperature:, 1. Homeothermic animals, 2. Poikilothermic animals., , Body temperature can be measured by placing the clini, cal thermometer in different parts of the body such as:, 1. Mouth (oral temperature), 2. Axilla (axillary temperature), 3. Rectum (rectal temperature), 4. Over the skin (surface temperature)., , HOMEOTHERMIC ANIMALS, Homeothermic animals are the animals in which the, body temperature is maintained at a constant level,, irrespective of the environmental temperature. Birds, and mammals including man belong to this category., They are also called warmblooded animals., , NORMAL BODY TEMPERATURE, Normal body temperature in human is 37°C (98.6°F),, when measured by placing the clinical thermometer in, the mouth (oral temperature). It varies between 35.8°C, and 37.3°C (96.4°F and 99.1°F)., , POIKILOTHERMIC ANIMALS, Poikilothermic animals are the animals in which the, body temperature is not constant. It varies according to, the environmental temperature. Amphibians and reptiles, are the poikilothermic animals. These animals are also, called coldblooded animals., , TEMPERATURE AT DIFFERENT PARTS, OF THE BODY, Axillary temperature is 0.3°C to 0.6°C (0.5°F to 1°F) lower, than the oral temperature. The rectal temperature is, , 0.3°C to 0.6°C (0.5°F to 1°F) higher than oral temperature.
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360 Section 5 t Renal Physiology and Skin, The superficial temperature (skin or surface temperature), varies between 29.5°C and 33.9°C (85.1°F and 93°F)., , is called hypothermia (Refer applied physiology in this, Chapter)., , Core Temperature, , HEAT BALANCE, , Core temperature is the average temperature of, structures present in deeper part of the body. The, core temperature is always more than oral or rectal, temperature. It is about 37.8°C (100°F)., , Regulation of body temperature depends upon the, balance between heat produced in the body and the, heat lost from the body., , VARIATIONS OF BODY TEMPERATURE, , HEAT GAIN OR HEAT PRODUCTION, IN THE BODY, , Physiological Variations, , Various mechanisms involved in heat production in the, body are:, , 1. Age, In infants, the body temperature varies in accordance, to environmental temperature for the first few days after, birth. It is because the temperature regulating system, does not function properly during infancy. In children,, the temperature is slightly (0.5°C) more than in adults, because of more physical activities. In old age, since the, heat production is less, the body temperature decreases, slightly., 2. Sex, In females, the body temperature is less because of low, basal metabolic rate, when compared to that of males., During menstrual phase it decreases slightly., 3. Diurnal variation, In early morning, the temperature is 1°C less. In the, afternoon, it reaches the maximum (about 1°C more, than normal)., 4. After meals, The body temperature rises slightly (0.5°C) after, meals., 5. Exercise, During exercise, the temperature raises due to, production of heat in muscles., 6. Sleep, During sleep, the body temperature decreases by, 0.5°C., 7. Emotion, During emotional conditions, the body temperature, increases., 8. Menstrual cycle, In females, immediately after ovulation, the temperature, rises (0.5°C to 1°C) sharply. It decreases (0.5°C) during, menstrual phase., , 1. Metabolic Activities, Major portion of heat produced in the body is due to the, metabolism of foodstuffs. It is called heat of metabolism., Heat production is more during metabolism of fat., About 9 calories of heat is produced during metabolism, of fats, when 1 L of oxygen is utilized. For the same, amount of oxygen, carbohydrate metabolism produces, 4.7 calories of heat. Protein metabolism produces 4.5, calories/L., Liver is the organ where maximum heat is produced, due to metabolic activities., 2. Muscular Activity, Heat is produced in the muscle both at rest and during, activities. During rest, heat is produced by muscle tone., Heat produced during muscular activity is called heat, of activity. About 80% of heat of activity is produced by, skeletal muscles., 3. Role of Hormones, Thyroxine and adrenaline increase the heat production, by accelerating the metabolic activities., 4. Radiation of Heat from the Environment, Body gains heat by radiation. It occurs when the environ, mental temperature is higher than the body temperature., 5. Shivering, Shivering refers to shaking of the body caused by rapid, involuntary contraction or twitching of the muscles as, during exposure to cold. Shivering is a compensatory, physiological mechanism in the body, during which, enormous heat is produced., , Pathological Variations, , 6. Brown Fat Tissue, , Abnormal increase in body temperature is called, hyperthermia or fever and decreased body temperature, , Brown adipose tissue is one of the two types of, adipose tissues, the other being white adipose tissue.
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Chapter 63 t Body Temperature 361, It produces enormous body heat, particularly in infants., Refer Chapter 47 for details., HEAT LOSS FROM THE BODY, Maximum heat is lost from the body through skin and, small amount of heat is lost through respiratory system,, kidney and GI tract. When environmental temperature is, less than body temperature, heat is lost from the body., Heat loss occurs by the following methods:, , HEAT LOSS CENTER, Heat loss center is situated in preoptic nucleus of anterior, hypothalamus. Neurons in preoptic nucleus are heat, sensitive nerve cells, which are called thermoreceptors, (Fig. 63.1)., Stimulation of preoptic nucleus results in cutaneous, vasodilatation and sweating. Removal or lesion of this, nucleus increases the body temperature., HEAT GAIN CENTER, , 1. Conduction, Three percent of heat is lost from the surface of the, body to other objects such as chair or bed, by means, of conduction., , Heat gain is otherwise known as heat production, center. It is situated in posterior hypothalamic nucleus., Stimulation of posterior hypothalamic nucleus causes, shivering. The removal or lesion of this nucleus leads to, fall in body temperature., , 2. Radiation, Sixty percent of heat is lost by means of radiation, i.e., transfer of heat by infrared electromagnetic radiation, from body to other objects through the surrounding air., 3. Convection, Fifteen percent of heat is lost from body to the air, by convection. First the heat is conducted to the air, surrounding the body and then carried away by air, currents, i.e. convection., 4. Evaporation – Insensible Perspiration, When water evaporates, heat is lost. Twenty two percent, of heat is lost through evaporation of water., Normally, a small quantity of water is continuously, evaporated from skin and lungs. We are not aware of it., So it is called the insensible perspiration or insensible, water loss. It is about 50 mL/hour. When body, temperature increases, sweat secretion is increased, and water evaporation is more with more of heat loss., 5. Panting, Panting is the rapid shallow breathing, associated with, dribbling of more saliva. In some animals like dogs which, do not have sweat glands, heat is lost by evaporation of, water from lungs and saliva by means of panting., , REGULATION OF BODY TEMPERATURE, Body temperature is regulated by hypothalamus, which, sets the normal range of body temperature. The set, point under normal physiological conditions is 37°C., Hypothalamus has two centers which regulate the, body temperature:, 1. Heat loss center, 2. Heat gain center., , MECHANISM OF TEMPERATURE REGULATION, When Body Temperature Increases, When body temperature increases, blood temperature, also increases. When blood with increased temperature, passes through hypothalamus, it stimulates the, thermoreceptors present in the heat loss center in, preoptic nucleus. Now, the heat loss center brings the, temperature back to normal by two mechanisms:, 1. Promotion of heat loss, 2. Prevention of heat production, 1. Promotion of heat loss, When body temperature increases, heat loss center, promotes heat loss from the body by two ways:, i. By increasing the secretion of sweat: When, sweat secretion increases, more water is lost, from skin along with heat, ii. By inhibiting sympathetic centers in posterior, hypothalamus: This causes cutaneous vaso, dilatation. Now, the blood flow through skin, increases causing excess sweating. It increases, the heat loss through sweat, leading to decrease, in body temperature., 2. Prevention of heat production, Heat loss center prevents heat production in the body, by inhibiting mechanisms involved in heat production,, such as shivering and chemical (metabolic) reactions., When Body Temperature Decreases, When the body temperature decreases, it is brought, back to normal by two mechanisms:, 1. Prevention of heat loss, 2. Promotion of heat production.
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362 Section 5 t Renal Physiology and Skin, , FIGURE 63.1: Regulation of body temperature, , 1. Prevention of heat loss, When body temperature decreases, sympathetic, centers in posterior hypothalamus cause cutaneous, vasoconstriction. This leads to decrease in blood flow to, skin and so the heat loss is prevented., 2. Promotion of heat production, Heat production is promoted by two ways:, i. Shivering: When body temperature is low, the heat, gain center stimulates the primary motor center, for shivering, situated in posterior hypothalamus, near the wall of the III ventricle and shivering, occurs. During shivering, enormous heat is pro, duced because of severe muscular activities., ii. Increased metabolic reactions: Sympathetic, centers, which are activated by heat gain, center, stimulate secretion of adrenaline and, , noradrenaline. These hormones, particularly, adrenaline increases the heat production by, accelerating cellular metabolic activities., Simultaneously, hypothalamus secretes thyro, tropinreleasing hormone. It causes release of, thyroidstimulating hormone from pituitary. It in, turn, increases release of thyroxine from thyroid., Thyroxine accelerates the metabolic activities in, the body and this increases heat production., Chemical thermogenesis: It is the process in, which heat is produced in the body by metabolic, activities induced by hormones., , APPLIED PHYSIOLOGY, HYPERTHERMIA – FEVER, Elevation of body temperature above the set point is, called hyperthermia, fever or pyrexia. Fever itself is not
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Chapter 63 t Body Temperature 363, an illness. But it is an important sign of something going, wrong in the body. It is the part of body’s response to, disease. Fever may be beneficial to body and on many, occasions, it plays an important role in helping the body, fight the diseases, particularly the infections., Classification of Fever, Fever is classified into three categories:, 1. Low-grade fever: When the body temperature rises, to 38°C to 39°C, (100.4°F to 102.2°F), 2. Moderate-grade fever: When the temperature rises, to 39°C to 40°C (102.2°F to 104°F), 3. High-grade fever: When the temperature rises, above 40°C to 42°C (104°F to 107.6°F)., Hyperpyrexia, Hyperpyrexia is the rise in body temperature beyond, 42°C (107.6°F). Hyperpyrexia results in damage of, body tissues. Further increase in temperature becomes, life threatening., Causes of Fever, 1. Infection: Certain substances (pyrogens) released, from bacteria or parasites affect the heatregulating, system in hypothalamus, resulting in the production, of excess heat and fever., 2. Hyperthyroidism: Increased basal metabolic rate, during hyperthyroidism causes fever, 3. Brain lesions: When lesion involves temperature, regulating centers, fever occurs., 4. Diabetes insipidus: In this condition, fever occurs, without any apparent cause., Signs and Symptoms, Signs and symptoms depend upon the cause of fever:, 1. Headache, 2. Sweating, 3. Shivering, 4. Muscle pain, 5. Dehydration, 6. Loss of appetite, 7. General weakness., Hyperpyrexia may result in:, 1. Confusion, 2. Hallucinations, 3. Irritability, 4. Convulsions., HYPOTHERMIA, Decrease in body temperature below 35°C (95°F) is, called hypothermia. It is considered as the clinical state, , of subnormal body temperature, when the body fails to, produce enough heat to maintain the normal activities., The major setback of this condition is the impairment of, metabolic activities of the body. When the temperature, drops below 31°C (87.8°F), it becomes fatal. Elderly, persons are more susceptible for hypothermia., Classification of Hypothermia, Hypothermia is classified into three categories:, 1. Mild hypothermia: When the body temperature falls, to 35°C to 33°C (95°F to 91.4°F), 2. Moderate hypothermia: When the body temperature, falls to 33°C to 31°C (91.4°F to 87.8°F), 3. Severe hypothermia: When the body temperature, falls below 31° C (87.8°F)., Causes of Hypothermia, 1., 2., 3., 4., 5., 6., 7., , Exposure to cold temperatures, Immersion in cold water, Drug abuse, Hypothyroidism, Hypopituitarism, Lesion in hypothalamus, Hemorrhage in certain parts of the brainstem,, particularly pons., , Signs and Symptoms, 1. Mild hypothermia, Uncontrolled intense shivering occurs. The affected, person can manage by self. But the movements, become less coordinated. The chillness causes pain, and discomfort., 2. Moderate hypothermia, Shivering slows down or stops but the muscles become, stiff. Mental confusion and apathy (lack of feeling, or emotions) occurs. Respiration becomes shallow,, followed by drowsiness. Pulse becomes weak and, blood pressure drops. Sometimes a strange behavior, develops., 3. Severe hypothermia, The person feels very weak and exhausted with, incoordination and physical disability. The skin becomes, chill and its color changes to bluish gray. Eyes are, dilated. The person looses consciousness gradually., Breathing slows down, followed by stiffness of arms and, legs. Pulse becomes very weak and blood pressure, decreases very much, resulting in unconsciousness., Further drop in body temperature leads to death.
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364 Questions in Renal Physiology and Skin, , QUESTIONS IN RENAL PHYSIOLOGY AND SKIN, , LONG QUESTIONS, 1. Describe the process of urine formation., 2. What are the different stages of urine formation?, Explain the role of glomerulus of nephron in the, formation of urine., 3. Give an account of role of renal tubule in the, process of urine formation., 4. What is countercurrent mechanism? Describe the, anatomical and physiological basis of counter, current mechanism in kidney., 5. Describe the mechanism involved in the, concentration of urine., 6. Describe the role of kidneys in maintaining acid, base balance., 7. Give an account of micturition., 8. What is normal body temperature? Explain heat, balance and regulation of body temperature. Add, a note on fever., , SHORT QUESTIONS, 1., 2., 3., 4., 5., 6., 7., 8., 9., 10., 11., 12., , Functions of kidney., Structure of nephron., Renal corpuscle., Juxtaglomerular apparatus., Reninangiotensin system., Peculiarities of renal circulation., Autoregulation of renal circulation., Glomerular filtration rate., Effective filtration pressure in kidney., Tubuloglomerular feedback., Glomerulotubular feedback., Reabsorption of glucose in renal tubule., , 13., 14., 15., 16., 17., 18., 19., 20., 21., 22., 23., 24., 25., 26., 27., 28., 29., 30., 31., 32., 33., 34., 35., 36., 37., 38., 39., 40., 41., 42., 43., 44., , Reabsorption of water in renal tubule., Reabsorption of sodium in renal tubules., Reabsorption of bicarbonate in renal tubules., Secretion in renal tubule., Renal failure., Renal medullary gradient., Countercurrent multiplier., Countercurrent exchanger., Actions of hormones on renal tubules., Acidification of urine., Role of kidney in maintaining acidbase balance., Plasma clearance., Measurement of glomerular filtration rate., Measurement of renal blood (or plasma) flow., Nerve supply to urinary bladder and sphincters., Cystometrogram., Micturition reflex., Abnormalities of urinary bladder., Dialysis/artificial kidney., Diuretics/loop diuretics., Renal failure., Structure of skin., Functions of skin., Sebaceous glands., Sweat glands., Differences between eccrine glands and apocrine, glands., Pheromones., Regulation of body temperature., Role of hypothalamus in temperature regulation., Heat balance., Hyperthermia., Hypothermia.
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Section, , 6, , 64., 65., 66., 67., 68., 69., 70., 71., 72., 73., , Endocrinology, , Introduction to Endocrinology .................................................................. 367, Hormones ................................................................................................ 371, Pituitary Gland ......................................................................................... 375, Thyroid Gland .......................................................................................... 388, Parathyroid Glands and Physiology of Bone ........................................... 399, Endocrine Functions of Pancreas ........................................................... 415, Adrenal Cortex ........................................................................................ 425, Adrenal Medulla ...................................................................................... 439, Endocrine Functions of Other Organs ..................................................... 444, Local Hormones ...................................................................................... 447
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Chapter, , Introduction to, Endocrinology, , 64, , INTRODUCTION, , , , , CELL-TO-CELL SIGNALING, CHEMICAL MESSENGERS, ENDOCRINE GLANDS, , METHODS OF STUDY, , , , , STUDY OF ENDOCRINE GLANDS, STUDY OF HORMONES, STUDY OF ENDOCRINE DISORDERS, , INTRODUCTION, , Classification of Chemical Messengers, , All the physiological activities of the body are regulated, by two major systems:, 1. Nervous system, 2. Endocrine system., These two systems interact with one another and, regulate the body functions. This section deals with, endocrine system and Section 10 deals with nervous, system. Endocrine system functions by secreting some, chemical substances called hormones., , Generally the chemical messengers are classified into, two types:, 1. Classical hormones secreted by endocrine glands, 2. Local hormones secreted from other tissues., , CELL-TO-CELL SIGNALING, Celltocell signaling refers to the transfer of information, from one cell to another. It is also called cell signaling, or intercellular communication. The cells of the body, communicate with each other through some chemical, substances called chemical messengers., CHEMICAL MESSENGERS, Chemical messengers are the substances involved in, cell signaling. These messengers are mainly secreted, from endocrine glands. Some chemical messengers are, secreted by nerve endings and the cells of several other, tissues also., All these chemical messengers carry the message, (signal) from the signaling cells (controlling cells) to, the target cells. The messenger substances may be the, hormones or hormonelike substances., , However, recently chemical messengers are classi, fied into four types:, 1. Endocrine messengers, 2. Paracrine messengers, 3. Autocrine messengers, 4. Neurocrine messengers., 1. Endocrine Messengers, Endocrine messengers are the classical hormones. A, hormone is defined as a chemical messenger, synthe, sized by endocrine glands and transported by blood to, the target organs or tissues (site of action)., Examples are growth hormone and insulin., 2. Paracrine Messengers, Paracrine messengers are the chemical messengers,, which diffuse from the control cells to the target cells, through the interstitial fluid. Some of these substances, directly enter the neighboring target cells through gap, junctions. Such substances are also called juxtacrine, messengers or local hormones., Examples are prostaglandins and histamine.
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368 Section 6 t Endocrinology, 3. Autocrine Messengers, , Neurohormone, , Autocrine messengers are the chemical messengers, that control the source cells which secrete them. So,, these messengers are also called intracellular chemical, , Neurohormone is a chemical substance that is released, by the nerve cell directly into the blood and transported, to the distant target cells., Examples are oxytocin, antidiuretic hormone and, hypothalamic releasing hormones., Some of the chemical mediators act as more than one, type of chemical messengers. For example, noradrena, line and dopamine function as classical hormones as, well as neurotransmitters. Similarly, histamine acts as, neurotransmitter and paracrine messenger., , mediators., , Examples are leukotrienes., 4. Neurocrine or Neural Messengers, Neurocrine or neural messengers are neurotransmitters, and neurohormones (Fig. 64.1)., Neurotransmitter, Neurotransmitter is an endogenous signaling molecule, that carries information form one nerve cell to another, nerve cell or muscle or another tissue., Examples are acetylcholine and dopamine., , ENDOCRINE GLANDS, Endocrine glands are the glands which synthesize and, release the classical hormones into the blood. Endocrine, glands are also called ductless glands because the, , FIGURE 64.1: Chemical messengers
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Chapter 64 t Introduction to Endocrinology 369, hormones secreted by them are released directly into, blood without any duct. Endocrine glands are distinct, from exocrine glands which release their secretions, through ducts., Endocrine glands play an important role in, homeostasis and control of various other activities in the, body through their hormones. Hormones are transported, by blood to target organs or tissues in different parts of, the body, where the actions are executed., Major endocrine glands: Fig. 64.2., Hormones secreted by endocrine glands: Table 64.1., Hormones secreted by gonads: Table 64.2., Hormones secreted by other organs: Table 64.3., Local hormones: Table 64.4., , METHODS OF STUDY, STUDY OF ENDOCRINE GLANDS, Methods followed to study an endocrine gland:, 1. Functional Anatomy, i., ii., iii., iv., v., , Situation, Divisions or parts, Histology, Blood supply, Nerve supply., , FIGURE 64.2: Diagram showing major endocrine glands, , 3. Evidences to Support the Functions of the Gland, , 2. Functions, i. Hormones secreted by the gland, ii. Actions of each hormone., , i. Effects of extirpation (removal) of the gland, ii. Effects of administration of extract or the hor, mone of the gland, iii. Clinical observation., , TABLE 64.1: Hormones secreted by major endocrine glands, Mineralocorticoids, , Anterior pituitary, , 1. Growth hormone (GH), 2. Thyroidstimulating hormone (TSH), 3. Adrenocorticotropic hormone (ACTH), 4. Follicle stimulating hormone (FSH), 5. Luteinizing hormone (LH), 6. Prolactin, , Posterior pituitary, , 1. Antidiuretic hormone (ADH), 2. Oxytocin, , Thyroid gland, , 1. Thyroxine (T4), 2. Triiodothyronine (T3), 3. Calcitonin, , Parathyroid gland, , Parathormone, , Pancreas –, Islets of Langerhans, , 1. Insulin, 2. Glucagon, 3. Somatostatin, 4. Pancreatic polypeptide, , 1. Aldosterone, 2. 11deoxycorticosterone, Glucocorticoids, Adrenal cortex, , 1. Cortisol, 2. Corticosterone, Sex hormones, 1. Androgens, 2. Estrogen, 3. Progesterone, , Adrenal medulla, , 1. Catecholamines, 2. Adrenaline (Epinephrine), 3. Noradrenaline (Norepinephrine), 4. Dopamine
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370 Section 6 t Endocrinology, TABLE 64.2: Hormones secreted by gonads, Testis, , 1. Testosterone, 2. Dihydrotestosterone, 3. Androstenedion, , Ovary, , 1. Estrogen, 2. Progesterone, , TABLE 64.3: Hormones secreted by other organs, Pineal gland, , Melatonin, , Thymus, , 1. Thymosin, 2. Thymin, , Kidney, , 1. Erythropoietin, 2. Thrombopoietin, 3. Renin, 4. 1,25dihydroxycholecalcifero (calcitriol), 5. Prostaglandins, , Heart, , 1. Atrial natriuretic peptide, 2. Brain natriuretic peptide, 3. Ctype natriuretic peptide, , Placenta, , 1. Human chorionic gonadotropin (HCG), 2. Human chorionic somatomammotropin, 3. Estrogen, 4. Progesterone, TABLE 64.4: Local hormones, , 1. Prostaglandins, 2. Thromboxanes, 3. Prostacyclin, 4. Leukotrienes, 5. Lipoxins, 6. Acetylcholine, , 7. Serotonin, 8. Histamine, 9. Substance P, 10. Heparin, 11. Bradykinin, 12. Gastrointestinal hormones, , 4. Regulation of Activity of the Gland, i. By other endocrine glands, ii. By other factors, iii. By feedback mechanism., 5. Applied Physiology, i. Disorders due to hyperactivity of the gland, ii. Disorders due to hypoactivity of the gland., STUDY OF HORMONES, A hormone is usually studied as follows:, 1. Source of secretion (gland as well as the cell that, secretes the hormone), 2. Chemistry, 3. Halflife, 4. Synthesis and metabolism, 5. Actions, 6. Mode of action, 7. Regulation of secretion, , 8. Applied physiology, i. Disorders due to hypersecretion of the hormone, ii. Disorders due to hyposecretion of the hormone., Half-life of the Hormones, Halflife is defined as the time during which half the, quantity of a hormone, drug or any substance is, metabolized or eliminated from circulation by biological, process. It is also defined as the time during which the, activity or potency of a substance is decreased to half, of its initial value., Halflife is also called biological halflife. Halflife, of a hormone denotes the elimination of that hormone, from circulation., STUDY OF ENDOCRINE DISORDERS, An endocrine disorder is studied by analyzing:, 1. Causes, 2. Signs and symptoms, 3. Syndrome., 1. Causes, Endocrine disorder may be due to the hyperactivity, or hypoactivity of the concerned gland. Secretion of, hormones increases during hyperactivity and decreases, during hypoactivity., 2. Signs and Symptoms, A sign is the feature of a disease as detected by the, doctor during the physical examination. So, it is the, objective physical evidence of disease found by the, examiner., Examples of signs are yellow coloration of skin and, mucous membrane in jaundice, paleness in anemia,, enlargement of liver, etc., A symptom is the feature of a disease felt by the, patient. So, it is the subjective evidence perceived by, the patient. In simple words, it is a noticeable change in, the body, experienced by the patient., Examples of symptoms are fever, itching, swelling,, tremor, etc., 3. Syndrome, Syndrome is the combination of signs and symptoms, (associated with a disease), which occur together, and suggest the presence of a certain disease or the, possibility of developing the disease., Examples are Stoke-Adams syndrome and, syndrome of inappropriate antidiuretic hormone hyper, secretion (SIADH).
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372 Section 6 t Endocrinology, PROTEIN HORMONES, Protein hormones are large or small peptides. Protein, hormones are secreted by pituitary gland, parathyroid, glands, pancreas and placenta (‘P’s)., TYROSINE DERIVATIVES, Two types of hormones, namely thyroid hormones and, adrenal medullary hormones are derived from the amino, acid tyrosine., , HORMONAL ACTION, INTRODUCTION, Hormone does not act directly on target cells. First it, combines with receptor present on the target cells and, forms a hormone-receptor complex. This hormonereceptor complex induces various changes or reactions, in the target cells., , FIGURE 65.1: Situation of hormonal receptors, , HORMONE RECEPTORS, Hormone receptors are the large proteins present in, the target cells. Each cell has thousands of receptors., Important characteristic feature of the receptors is that,, each receptor is specific for one single hormone, i.e., each receptor can combine with only one hormone., Thus, a hormone can act on a target cell, only if the, target cell has the receptor for that particular hormone., Situation of the Hormone Receptors, , Hormone in the form of hormone-receptor complex, enters the target cell by means of endocytosis and, executes the actions. The whole process is called, internalization., , After internalization, some receptors are recycled,, whereas many of them are degraded and new receptors, are formed. Formation of new receptors takes a long, time. So, the number of receptors decreases when, hormone level increases., , Hormone receptors are situated either in cell membrane, or cytoplasm or nucleus of the target cells as follows:, 1. Cell membrane: Receptors of protein hormones and, adrenal medullary hormones (catecholamines) are, situated in the cell membrane (Fig. 65.1), 2. Cytoplasm: Receptors of steroid hormones are, situated in the cytoplasm of target cells, 3. Nucleus: Receptors of thyroid hormones are in the, nucleus of the cell., , MECHANISM OF HORMONAL ACTION, , Regulation of Hormone Receptors, , BY ALTERING PERMEABILITY, OF CELL MEMBRANE, , Receptor proteins are not static components of the, cell. Their number increases or decreases in various, conditions., Generally, when a hormone is secreted in excess,, the number of receptors of that hormone decreases due, to binding of hormone with receptors. This process is, called down regulation. During the deficiency of the, hormone, the number of receptor increases, which is, called upregulation., , Hormone does not act on the target cell directly. It, combines with receptor to form hormone-receptor, complex. This complex executes the hormonal action, by any one of the following mechanisms:, 1. By altering permeability of cell membrane, 2. By activating intracellular enzyme, 3. By acting on genes., , Neurotransmitters in synapse or neuromuscular junction, act by changing the permeability of postsynaptic, membrane., For example, in a neuromuscular junction, when, an impulse (action potential) reaches the axon terminal, of the motor nerve, acetylcholine is released from the, vesicles. Acetylcholine increases the permeability of, the postsynaptic membrane for sodium, by opening the
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Chapter 65 t Hormones 373, ligand-gated sodium channels. So, sodium ions enter the, neuromuscular junction from ECF through the channels, and cause the development of endplate potential. Refer, Chapter 32 for details., BY ACTIVATING INTRACELLULAR ENZYME, Protein hormones and the catecholamines act by, activating the intracellular enzymes., First Messenger, The hormone which acts on a target cell, is called first, messenger or chemical mediator. It combines with the, receptor and forms hormone-receptor complex., Second Messenger, Hormone-receptor complex activates the enzymes of, the cell and causes the formation of another substance, called the second messenger or intracellular hormonal, mediator., , Second messenger produces the effects of the, hormone inside the cells. Protein hormones and the, catecholamines act through second messenger. Most, common second messenger is cyclic AMP., Cyclic AMP, Cyclic AMP, cAMP or cyclic adenosine 3’5’monophosphate acts as a second messenger for protein, hormones and catecholamines., Formation of cAMP – Role of G proteins, G proteins or guanosine nucleotide-binding proteins, are the membrane proteins situated on the inner surface, of cell membrane. These proteins play an important role, in the formation of cAMP, Each G protein molecule is made up of trimeric, (three) subunits called α, β and γ subunits. The α-subunit, is responsible for most of the biological actions. It is, bound with guanosine diphosphate (GDP) and forms, α-GDP unit. The α-subunit is also having the intrinsic, enzyme activity called GTPase activity. The β and γ, subunits always bind together to form the β-γ dimmer., It can also bring about some actions. In the inactivated, G protein, both α-GDP unit and β-γ dimmer are united, (Fig. 65.2: Stage 1)., Sequence of events in the formation of cAMP, i. Hormone binds with the receptor in the cell membrane and forms the hormone-receptor complex, ii. It activates the G protein, iii. G protein releases GDP from α-GDP unit, , FIGURE 65.2: Mode of action of protein hormones and catecholamines. H = Hormone. R = Receptor, α, β, γ = G protein, GDP, = Guanosine diphosphate, GTP = Guanosine triphosphate,, ECF = Extracellular fluid, cAMP = Cyclic adenosine 3’5’-monophosphate, ATP = Adenosine triphosphate., , iv. The α-subunit now binds with a new molecule of, GTP, i.e. the GDP is exchanged for GTP, v. This exchange triggers the dissociation of α-GTP, unit and β-γ dimmer from the receptor, vi. Both α-GTP unit and β-γ dimmer now activate the, second messenger pathways (Fig. 65.2: Stage 2), vii. The α-GTP unit activates the enzyme adenyl, cyclase, which is also present in the cell membrane. Most of the adenyl cyclase protrudes into, the cytoplasm of the cell from inner surface of, the cell membrane, viii. Activated adenyl cyclase converts the adenosine triphosphate of the cytoplasm into cyclic, adenosine monophosphate (cAMP), When the action is over, α-subunit hydrolyzes, the attached GTP to GDP by its GTPase activity. This, allows the reunion of α-subunit with β-γ dimmer and, commencing a new cycle (Fig. 65.2: Stage 1)., Actions of cAMP, Cyclic AMP executes the actions of hormone inside the, cell by stimulating the enzymes like protein kinase A.
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374 Section 6 t Endocrinology, Cyclic AMP produces the response, depending upon, the function of the target cells through these enzymes., Response produced by cAMP, Cyclic AMP produces one or more of the following, responses:, i. Contraction and relaxation of muscle fibers, ii. Alteration in the permeability of cell membrane, iii. Synthesis of substances inside the cell, iv. Secretion or release of substances by target cell, v. Other physiological activities of the target cell., Other Second Messengers, In addition to cAMP, some other substances also act, like second messengers for some of the hormones in, target cells., , FIGURE 65.3: Mode of action of steroid hormones. Thyroid, hormones also act in the similar way but their receptors are in, the nucleus. HR = Hormone-receptor complex, , i. Calcium ions and calmodulin, Many hormones act by increasing the calcium ion, which, fucntions as second messenger along with another, protein called calmodulin or troponin C. Calmodulin is, present in smooth muscles and troponin C is present, in skeletal muscles. Calcium-calmodulin complex, activates various enzymes in the cell, which cause the, physiological responses. Common enzyme activated, by calcium-calmodulin complex is the myosin kinase in, smooth muscle. Myosin kinase catalyses the reactions,, resulting in muscular contraction (Chapter 33)., In the skeletal muscle, calcium ions bind with, troponin C, which is similar to calmodulin (Chapter 31)., ii. Inositol triphosphate, Inositol, triphosphate, (IP3), is, formed, from, phosphatidylinositol biphosphate (PIP2)., Hormone-receptor complex activates the enzyme, phospholipase, which converts PIP2 into IP3. IP3 acts on, protein kinase C and causes the physiological response, by the release of calcium ions into the cytoplasm of, target cell., iii. Diacylglycerol, Diacylglycerol (DAG) is also produced from PIP2. It acts, via protein kinase C., , iv. Cyclic guanosine monophosphate, Cyclic guanosine monophosphate (cGMP) functions, like cAM P by acting on protein kinase A., BY ACTING ON GENES, Thyroid and steroid hormones execute their function by, acting on genes in the target cells (Fig. 65.3)., Sequence of Events during Activation of Genes, i. Hormone enters the interior of cell and binds with, receptor in cytoplasm (steroid hormone) or in, nucleus (thyroid hormone) and forms hormonereceptor complex, ii. Hormone-receptor complex moves towards the, DNA and binds with DNA, iii. This increases transcription of mRNA, iv. The mRNA moves out of nucleus and reaches, ribosomes and activates them, v. Activated ribosomes produce large quantities of, proteins, vi. These proteins produce physiological responses, in the target cells.
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Chapter, , Pituitary Gland, , 66, , INTRODUCTION, , , , , DIVISIONS, DEVELOPMENT, REGULATION OF SECRETIONS, , ANTERIOR PITUITARY OR ADENOHYPOPHYSIS, , , , , , , , PARTS, HISTOLOGY, REGULATION, HORMONES, GROWTH HORMONE, OTHER HORMONES, , POSTERIOR PITUITARY OR NEUROHYPOPHYSIS, , , , , , , PARTS, HISTOLOGY, HORMONES, ANTIDIURETIC HORMONE, OXYTOCIN, , APPLIED PHYSIOLOGY – DISORDERS OF PITUITARY GLAND, , , , , , , HYPERACTIVITY OF ANTERIOR PITUITARY, HYPOACTIVITY OF ANTERIOR PITUITARY, HYPERACTIVITY OF POSTERIOR PITUITARY, HYPOACTIVITY OF POSTERIOR PITUITARY, HYPOACTIVITY OF ANTERIOR AND POSTERIOR PITUITARY, , INTRODUCTION, Pituitary gland or hypophysis is a small endocrine, gland with a diameter of 1 cm and weight of 0.5 to 1 g., It is situated in a depression called ‘sella turcica’,, present in the sphenoid bone at the base of skull. It is, connected with the hypothalamus by the pituitary stalk, or hypophyseal stalk., DIVISIONS OF PITUITARY GLAND, Pituitary gland is divided into two divisions:, 1. Anterior pituitary or adenohypophysis, 2. Posterior pituitary or neurohypophysis., , Both the divisions are situated close to each other., Still both are entirely different in their development,, structure and function., Between the two divisions, there is a small and, relatively avascular structure called pars intermedia., Actually, it forms a part of anterior pituitary., DEVELOPMENT OF PITUITARY GLAND, Both the divisions of pituitary glands develop from, different sources., Anterior pituitary is ectodermal in origin and arises, from the pharyngeal epithelium as an upward growth, known as Rathke pouch.
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376 Section 6 t Endocrinology, Posterior pituitary is neuroectodermal in origin and, arises from hypothalamus as a downward diverticulum., Rathke pouch and the downward diverticulum from, hypothalamus grow towards each other and meet in the, midway between the roof of the buccal cavity and base, of brain. There, the two structures lie close together., , HISTOLOGY, , REGULATION OF SECRETION, , Chromophobe Cells, , Hypothalamo-hypophyseal Relationship, The relationship between hypothalamus and pituitary, gland is called hypothalamo-hypophyseal relationship., Hormones secreted by hypothalamus are transported to, anterior pituitary and posterior pituitary. But the mode of, transport of these hormones is different., Hormones from hypothalamus are transported to, anterior pituitary through hypothalamo-hypophysial portal, blood vessels. But, the hormones from hypothalamus, to posterior pituitary are transported by nerve fibers of, hypothalamo-hypophyseal tract (see below for details)., , ANTERIOR PITUITARY OR, ADENOHYPOPHYSIS, Anterior pituitary is also known as the master gland, because it regulates many other endocrine glands, through its hormones., PARTS, Anterior pituitary consists of three parts (Fig. 66.1):, 1. Pars distalis, 2. Pars tuberalis, 3. Pars intermedia., , Anterior pituitary has two types of cells, which have, different staining properties:, 1. Chromophobe cells, 2. Chromophil cells., , Chromophobe cells do not possess granules and stain, poorly. These cells form 50% of total cells in anterior, pituitary. Chromophobe cells are not secretory in nature,, but are the precursors of chromophil cells., Chromophil Cells, Chromophil cells contain large number of granules and, are darkly stained., Types of chromophil cells, Chromophil cells are classified by two methods., 1. Classification on the basis of staining property:, Chromophil cells are divided into two types:, i. Acidophilic cells or alpha cells, which form 35%, ii. Basophilic cells or beta cells, which form 15%., 2. Classification on the basis of secretory nature:, Chromophil cells are classified into five types:, i. Somatotropes, which secrete growth hormone, ii. Corticotropes, which secrete adrenocorticotropic, hormone, iii. Thyrotropes, which secrete thyroid-stimulating, hormone (TSH), iv. Gonadotropes, which secrete follicle-stimulating, hormone (FSH) and luteinizing hormone (LH), v. Lactotropes, which secrete prolactin., Somatotropes and lactotropes are acidophilic cells,, whereas others are basophilic cells. Somatotropes form, about 30% to 40% of the chromophil cells. So, pituitary, tumors that secrete large quantities of human growth, hormone are called acidophilic tumors., REGULATION OF ANTERIOR, PITUITARY SECRETION, , FIGURE 66.1: Parts of pituitary gland, Adenohypophysis, Neurohypophysis, , Hypothalamus controls anterior pituitary by secreting, the releasing and inhibitory hormones (factors), which, are called neurohormones. These hormones from, hypothalamus are transported anterior pituitary through, hypothalamo-hypophyseal portal vessels., Some special nerve cells present in various parts, hypothalamus send their nerve fibers (axons) to median, eminence and tuber cinereum. These nerve cells, synthesize the hormones and release them into median
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Chapter 66 t Pituitary Gland 377, eminence and tuber cinereum. From here, the hormones, are transported by blood via hypothalamo-hypophyseal, portal vessels to anterior pituitary (Fig. 66.2)., Releasing and Inhibitory Hormones, Secreted by Hypothalamus, 1. Growth hormone-releasing hormone (GHRH):, Stimulates the release of growth hormone, 2. Growth hormone-releasing polypeptide (GHRP):, Stimulates the release of GHRH and growth hormone, 3. Growth hormone-inhibitory hormone (GHIH) or, somatostatin: Inhibits the growth hormone release, 4. Thyrotropic-releasing hormone (TRH): Stimulates, the release of thyroid stimulating hormone, 5. Corticotropin-releasing hormone (CRH): Stimulates, the release of adrenocorticotropin, 6. Gonadotropin-releasing hormone (GnRH): Stimulates the release of gonadotropins, FSH and LH, 7. Prolactin-inhibitory hormone (PIH): Inhibits prolactin, secretion. It is believed that PIH is dopamine., HORMONES SECRETED BY, ANTERIOR PITUITARY, Six hormones are secreted by the anterior pituitary:, 1. Growth hormone (GH) or somatotropic hormone, (STH), 2. Thyroid-stimulating hormone (TSH) or thyrotropic, hormone, 3. Adrenocorticotropic hormone (ACTH), 4. Follicle-stimulating hormone (FSH), , 5. Luteinizing hormone (LH) in females or interstitialcell-stimulating hormone (ICSH) in males, 6. Prolactin., Recently, the hormone β-lipotropin is found to be, secreted by anterior pituitary., Tropic Hormones, First five hormones of anterior pituitary stimulate the other, endocrine glands. Growth hormone also stimulates the, secretory activity of liver and other tissues. Therefore,, these five hormones are called tropic hormones., Prolactin is concerned with milk secretion., Gonadotropic Hormones, Follicle-stimulating hormone and the luteinizing hormone are together called gonadotropic hormones or, gonadotropins because of their action on gonads., GROWTH HORMONE, Source of Secretion, Growth hormone is secreted by somatotropes which are, the acidophilic cells of anterior pituitary., Chemistry, Blood Level and Daily Output, GH is protein in nature, having a single-chain polypeptide, with 191 amino acids. Its molecular weight is 21,500., Basal level of GH concentration in blood of normal, adult is up to 300 g/dL and in children, it is up to 500 ng/, dL. Its daily output in adults is 0.5 to1.0 mg., Transport, Growth hormone is transported in blood by GH-binding, proteins (GHBPs)., Half-life and Metabolism, Half-life of circulating growth hormone is about 20, minutes. It is degraded in liver and kidney., Actions of Growth Hormone, , FIGURE 66.2: Blood supply to pituitary gland, , GH is responsible for the general growth of the body., Hypersecretion of GH causes enormous growth of the, body, leading to gigantism. Deficiency of GH in children, causes stunted growth, leading to dwarfism., GH is responsible for the growth of almost all tissues, of the body, which are capable of growing. It increases, the size and number of cells by mitotic division. GH also, causes specific differentiation of certain types of cells, like bone cells and muscle cells.
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378 Section 6 t Endocrinology, GH also acts on the metabolism of all the three, major types of foodstuffs in the body, viz. proteins, lipids, and carbohydrates., 1. On metabolism, GH increases the synthesis of proteins, mobilization of, lipids and conservation of carbohydrates., a. On protein metabolism, GH accelerates the synthesis of proteins by:, i. Increasing amino acid transport through cell, membrane: The concentration of amino acids, in the cells increases and thus, the synthesis of, proteins is accelerated., ii. Increasing ribonucleic acid (RNA) translation:, GH increases the translation of RNA in the, cells (Refer Chapter 1 for details of translation)., Because of this, ribosomes are activated and, more proteins are synthesized., GH can increase the RNA translation even, without increasing the amino acid transport into, the cells., iii. Increasing transcription of DNA to RNA: It also, stimulates the transcription of DNA to RNA., RNA, in turn accelerates the synthesis of, proteins in the cells (Refer Chapter 1 for details, of transcription)., iv. Decreasing catabolism of protein: GH inhibits, the breakdown of cellular protein. It helps in the, building up of tissues., v. Promoting anabolism of proteins indirectly: GH, increases the release of insulin (from β-cells of, islets in pancreas), which has anabolic effect on, proteins., b. On fat metabolism, GH mobilizes fats from adipose tissue. So, the, concentration of fatty acids increases in the body fluids., These fatty acids are used for the production of energy, by the cells. Thus, the proteins are spared., During the utilization of fatty acids for energy, production, lot of acetoacetic acid is produced by liver, and is released into the body fluids, leading to ketosis., Sometimes, excess mobilization of fat from the adipose, tissue causes accumulation of fat in liver, resulting in, fatty liver., , c. On carbohydrate metabolism, Major action of GH on carbohydrates is the conservation, of glucose., Effects of GH on carbohydrate metabolism:, i. Decrease in the peripheral utilization of glucose, for the production of energy: GH reduces the, , peripheral utilization of glucose for energy, production. It is because of the formation, of acetyl-CoA during the metabolism of fat,, influenced by GH. The acetyl-CoA inhibits the, glycolytic pathway. Moreover, since the GH, increases the mobilization of fat, more fatty acid, is available for the production of energy. By this, way, GH reduces the peripheral utilization of, glucose for energy production., ii. Increase in the deposition of glycogen in the, cells: Since glucose is not utilized for energy, production by the cells, it is converted into, glycogen and deposited in the cells., iii. Decrease in the uptake of glucose by the cells:, As glycogen deposition increases, the cells, become saturated with glycogen. Because of, this, no more glucose can enter the cells from, blood. So, the blood glucose level increases., iv. Diabetogenic effect of GH: Hypersecretion of, GH increases blood glucose level enormously., It causes continuous stimulation of the β-cells, in the islets of Langerhans in pancreas and, increase in secretion of insulin. In addition, to this, the GH also stimulates β-cells directly, and causes secretion of insulin. Because of, the excess stimulation, β-cells are burnt out at, one stage. This causes deficiency of insulin,, leading to true diabetes mellitus or full-blown, diabetes mellitus. This effect of GH is called the, diabetogenic effect., , 2. On bones, In embryonic stage, GH is responsible for the, differentiation and development of bone cells. In later, stages, GH increases the growth of the skeleton. It, increases both the length as well as the thickness of, the bones., In bones, GH increases:, i. Synthesis and deposition of proteins by, chondrocytes and osteogenic cells, ii. Multiplication of chondrocytes and osteogenic cells, by enhancing the intestinal calcium absorption, iii. Formation of new bones by converting chondrocytes into osteogenic cells, iv. Availability of calcium for mineralization of bone, matrix., GH increases the length of the bones, until epiphysis, fuses with shaft, which occurs at the time of puberty., After the epiphyseal fusion, length of the bones cannot, be increased. However, it stimulates the osteoblasts, strongly. So, the bone continues to grow in thickness, throughout the life. Particularly, the membranous bones
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Chapter 66 t Pituitary Gland 379, such as the jaw bone and the skull bones become, thicker under the influence of GH., Hypersecretion of GH before the fusion of epiphysis, with the shaft of the bones causes enormous growth of, the skeleton, leading to a condition called gigantism., Hypersecretion of GH after the fusion of epiphysis, with the shaft of the bones leads to a condition called, acromegaly., , Mode of Action of GH – Somatomedin, GH acts on bones, growth and protein metabolism, through somatomedin secreted by liver. GH stimulates, the liver to secrete somatomedin. Sometimes, in spite, of normal secretion of GH, growth is arrested (dwarfism), due to the absence or deficiency of somatomedin., Somatomedin, Somatomedin is defined as a substance through, which growth hormone acts. It is a polypeptide with the, molecular weight of about 7,500., Types of somatomedin, Somatomedins are of two types:, i. Insulin-like growth factor-I (IGF-I), which is also, called somatomedin C, ii. Insulin-like growth factor-II., Somatomedin C (IGF-I) acts on the bones and, protein metabolism. Insulin-like growth factor-II plays, an important role in the growth of fetus., Duration of action of GH and somatomedin C, GH is transported in blood by loose binding with plasma, protein. So, at the site of action, it is released from, plasma protein rapidly. Its action also lasts only for a short, duration of 20 minutes. But, the somatomedin C binds, with plasma proteins very strongly. Because of this, the, molecules of somatomedin C are released slowly from, the plasma proteins. Thus, it can act continuously for a, longer duration. The action of somatomedin C lasts for, about 20 hours., Mode of action of somatomedin C, Somatomedin C acts through the second messenger, called cyclic AMP (refer previous Chapter)., Growth hormone receptor, GH receptor is called growth hormone secretagogue, (GHS) receptor. It is a transmembrane receptor, belonging to cytokine receptor family. GH binds with the receptor, situated mainly in liver cells and forms the hormonereceptor complex. Hormone-receptor complex induces, various intracellular enzyme pathways, resulting in, , somatomedin secretion. Somatomedin in turn, executes, the actions of growth hormone., Regulation of GH Secretion, Growth hormone secretion is altered by various factors., However, hypothalamus and feedback mechanism play, an important role in the regulation of GH secretion, GH secretion is stimulated by:, 1. Hypoglycemia, 2. Fasting, 3. Starvation, 4. Exercise, 5. Stress and trauma, 6. Initial stages of sleep., GH secretion is inhibited by:, 1. Hyperglycemia, 2. Increase in free fatty acids in blood, 3. Later stages of sleep., Role of hypothalamus in the secretion of GH, Hypothalamus regulates GH secretion via three, hormones:, 1. Growth hormone-releasing hormone (GHRH):, It increases the GH secretion by stimulating the, somatotropes of anterior pituitary, 2. Growth hormone-releasing polypeptide (GHRP): It, increases the release of GHRH from hypothalamus, and GH from pituitary, 3. Growth hormone-inhibitory hormone (GHIH) or, somatostatin: It decreases the GH secretion., Somatostatin is also secreted by delta cells of islets, of Langerhans in pancreas., These three hormones are transported from, hypothalamus to anterior pituitary by hypothalamohypophyseal portal blood vessels., Feedback control, GH secretion is under negative feedback control, (Chapter 4). Hypothalamus releases GHRH and GHRP,, which in turn promote the release of GH from anterior, pituitary. GH acts on various tissues. It also activates, the liver cells to secrete somatomedin C (IGF-I)., Now, the somatomedin C increases the release, of GHIH from hypothalamus. GHIH, in turn inhibits the, release of GH from pituitary. Somatomedin also inhibits, release of GHRP from hypothalamus. It acts on pituitary, directly and inhibits the secretion of GH (Fig. 66.3)., GH inhibits its own secretion by stimulating the, release of GHIH from hypothalamus. This type of, feedback is called short-loop feedback control. Similarly,, GHRH inhibits its own release by short-loop feedback, control.
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380 Section 6 t Endocrinology, Whenever, the blood level of GH decreases, the, GHRH is secreted from the hypothalamus. It in turn, causes secretion of GH from pituitary., Role of ghrelin in the secretion of GH, Ghrelin is a peptide hormone synthesized by epithelial, cells in the fundus of stomach. It is also produced in, smaller amount in hypothalamus, pituitary, kidney and, placenta (Chapter 44). Ghrelin promotes secretion of, GH by stimulating somatotropes directly., OTHER HORMONES OF ANTERIOR PITUITARY, Thyroid-stimulating Hormone (TSH), TSH is necessary for the growth and secretory activity, of the thyroid gland. It has many actions on the thyroid, gland. Refer Chapter 67 for details of TSH., Adrenocorticotropic Hormone (ACTH), ACTH is necessary for the structural integrity and the, secretory activity of adrenal cortex. It has other functions, also. Refer Chapter 70 for details of ACTH., , Follicle-stimulating Hormone (FSH), Follicle-stimulating hormone is a glycoprotein made up, of one α-subunit and a β-subunit. The α-subunit has 92, amino acids and β-subunit has 118 amino acids. The, half-life of FSH is about 3 to 4 hours., Actions of FSH, In males, FSH acts along with testosterone and, accelerates the process of spermeogenesis (refer, Chapter 74 for details)., In females FSH:, 1. Causes the development of graafian follicle from, primordial follicle, 2. Stimulates the theca cells of graafian follicle and, causes secretion of estrogen (refer Chapter 79 for, details), 3. Promotes the aromatase activity in granulosa cells,, resulting in conversion of androgens into estrogen, (Chapter 80)., Luteinizing Hormone (LH), LH is a glycoprotein made up of one α-subunit and, one β-subunit. The α-subunit has 92 amino acids and, β-subunit has 141 amino acids. The half-life of LH is, about 60 minutes., Actions of LH, In males, LH is known as interstitial cell-stimulating, hormone (ICSH) because it stimulates the interstitial, cells of Leydig in testes. This hormone is essential for, the secretion of testosterone from Leydig cells (Chapter, 74)., In females, LH:, 1. Causes maturation of vesicular follicle into graafian, follicle along with follicle-stimulating hormone, 2. Induces synthesis of androgens from theca cells of, growing follicle, 3. Is responsible for ovulation, 4. Is necessary for the formation of corpus luteum, 5. Activates the secretory functions of corpus luteum., Prolactin, , FIGURE 66.3: Regulation of GH secretion. GHIH = Growth, hormone-inhibiting hormone, GHRH = Growth hormonereleasing hormone, GHRP = Growth hormone-releasing, polypeptide. Growth hormone and somatomedin stimulate, hypothalamus to release GHIH . Somatomedin inhibits anterior, pituitary directly. Solid green line = Stimulation/secretion,, Dashed red line = Inhibition., , Prolactin is a single chain polypeptide with 199 amino, acids. Its half-life is about 20 minutes. Prolactin is, necessary for the final preparation of mammary glands, for the production and secretion of milk., Prolactin acts directly on the epithelial cells of mammary glands and causes localized alveolar hyperplasia., Refer Chapter 87 for details.
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Chapter 66 t Pituitary Gland 381, β-lipotropin, β-lipotropin is a polypeptide hormone with 31 amino, acids. It mobilizes fat from adipose tissue and promotes, lipolysis. It also forms the precursor of endorphins. This, hormone acts through the adenyl cyclase., , POSTERIOR PITUITARY, OR NEUROHYPOPHYSIS, PARTS, Posterior pituitary consists of three parts:, 1. Pars nervosa or infundibular process, 2. Neural stalk or infundibular stem, 3. Median eminence., Pars tuberalis of anterior pituitary and the neural, stalk of posterior pituitary together form the hypophyseal, stalk., , HISTOLOGY, Posterior pituitary is made up of neural type of cells, called pituicytes and unmyelinated nerve fibers., Pituicytes, Pituicytes are the fusiform cells derived from glial cells., These cells have several processes and brown pigment granules. Pituicytes act as supporting cells and do, not secrete any hormone., Unmyelinated Nerve Fibers, , nerve fibers of hypothalamo-hypophyseal tract (Fig., 66.4), by means of axonic flow. Proteins involved in, transport of these hormones are called neurophysins, (see below)., In the posterior pituitary, these hormones are, stored at the nerve endings. Whenever, the impulses, from hypothalamus reach the posterior pituitary, these, hormones are released from the nerve endings into, the circulation. Hence, these two hormones are called, neurohormones., , Experimental Evidence, Secretion of posterior pituitary hormones in hypothalamus, and their transport to posterior pituitary are proved, by experimental evidences. When the pituitary stalk, is cut above the pituitary gland, by leaving the entire, hypothalamus intact, the hormones drip through the cut, end of the nerves in the pituitary stalk. This proves the, fact that the hormones are secreted by hypothalamus., Neurophysins, Neurophysins are the binding proteins which transport, ADH and oxytocin from hypothalamus to posterior, pituitary via hypothalamo-hypophyseal tract and storage, of these hormones in posterior pituitary. Neurophysin I or, oxytocin-neurophysin is the binding protein for oxytocin, and neurophysin II or ADH-neurophysin is the binding, protein for ADH., , Unmyelinated nerve fibers come from supraoptic and, paraventricular nuclei of the hypothalamus through the, pituitary stalk., Other Structures, Posterior pituitary also has numerous blood vessels,, hyaline bodies, neuroglial cells and mast cells., HORMONES OF POSTERIOR PITUITARY, Posterior pituitary hormones are:, 1. Antidiuretic hormone (ADH) or vasopressin, 2. Oxytocin., Source of Secretion of Posterior, Pituitary Hormones, Actually, the posterior pituitary does not secrete any, hormone. ADH and oxytocin are synthesized in the, hypothalamus. From hypothalamus, these two hormones, are transported to the posterior pituitary through the, , FIGURE 66.4: Hypothalamo-hypophyseal tracts
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382 Section 6 t Endocrinology, ANTIDIURETIC HORMONE, Source of Secretion, Antidiuretic hormone (ADH) is secreted mainly by, supraoptic nucleus of hypothalamus. It is also secreted, by paraventricular nucleus in small quantity. From, here, this hormone is transported to posterior pituitary, through the nerve fibers of hypothalamo-hypophyseal, tract, by means of axonic flow., Chemistry and Half-life, Antidiuretic hormone is a polypeptide containing 9 amino, acids. Its half-life is 18 to 20 minutes., Actions, Antidiuretic hormone has two actions:, 1.Retention of water, 2.Vasopressor action., 1. Retention of water, Major function of ADH is retention of water by acting, on kidneys. It increases the facultative reabsorption of, water from distal convoluted tubule and collecting duct, in the kidneys (Chapter 52)., In the absence of ADH, the distal convoluted tubule, and collecting duct are totally impermeable to water. So,, reabsorption of water does not occur in the renal tubules, and dilute urine is excreted. This leads to loss of large, amount of water through urine. This condition is called, diabetes insipidus and the excretion of large amount of, water is called diuresis., Mode of action on renal tubules, ADH increases water reabsorption in tubular epithelial, membrane by regulating the water channel proteins, called aquaporins through V2 receptors (Chapter 52)., 2. Vasopressor action, In large amount, ADH shows vasoconstrictor action., Particularly, causes constriction of the arteries in all, parts of the body. Due to vasoconstriction, the blood, pressure increases. ADH acts on blood vessels through, V1A receptors., However, the amount of ADH required to cause the, vasopressor effect is greater than the amount required, to cause the antidiuretic effect., , Potent stimulants for ADH secretion are:, 1. Decrease in the extracellular fluid (ECF) volume, 2. Increase in osmolar concentration in the ECF., Role of osmoreceptors, Osmoreceptors are the receptors which give response, to change in the osmolar concentration of the blood., These receptors are situated in the hypothalamus near, supraoptic and paraventricular nuclei. When osmolar, concentration of blood increases, the osmoreceptors, are activated. In turn, the osmoreceptors stimulate the, supraoptic and paraventricular nuclei which send motor, impulses to posterior pituitary through the nerve fibers, and cause release of ADH. ADH causes reabsorption, of water from the renal tubules. This increases ECF, volume and restores the normal osmolarity., OXYTOCIN, Source of Secretion, Oxytocin is secreted mainly by paraventricular nucleus, of hypothalamus. It is also secreted by supraoptic, nucleus in small quantity and it is transported from, hypothalamus to posterior pituitary through the nerve, fibers of hypothalamo-hypophyseal tract., In the posterior pituitary, the oxytocin is stored in, the nerve endings of hypothalamo-hypophyseal tract., When suitable stimuli reach the posterior pituitary from, hypothalamus, oxytocin is released into the blood., Oxytocin is secreted in both males and females., Chemistry and Half-life, Oxytocin is a polypeptide having 9 amino acids. It has a, half-life of about 6 minutes., Actions in Females, In females, oxytocin acts on mammary glands and, uterus., Action of oxytocin on mammary glands, Oxytocin causes ejection of milk from the mammary, glands. Ducts of the mammary glands are lined by myoepithelial cells. Oxytocin causes contraction of the myoepithelial cells and flow of milk from alveoli of mammary, glands to the exterior through duct system and nipple., The process by which the milk is ejected from alveoli of, mammary glands is called milk ejection reflex or milk letdown reflex. It is one of the neuroendocrine reflexes., , Regulation of Secretion, , Milk ejection reflex, , ADH secretion depends upon the volume of body fluid, and the osmolarity of the body fluids., , Plenty of touch receptors are present on the mammary, glands, particularly around the nipple. When the
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Chapter 66 t Pituitary Gland 383, infant suckles mother nipple, the touch receptors, are stimulated. The impulses discharged from touch, receptors are carried by the somatic afferent nerve, fibers to paraventricular and supraoptic nuclei of, hypothalamus., Now hypothalamus, in turn sends impulses to the, posterior pituitary through hypothalamo-hypophyseal, tract. Afferent impulses cause release of oxytocin into the, blood. When the hormone reaches the mammary gland,, it causes contraction of myoepithelial cells, resulting in, ejection of milk from mammary glands (Fig. 66.5)., As this reflex is initiated by the nervous factors, and completed by the hormonal action, it is called a, neuroendocrine reflex. During this reflex, large amount of, oxytocin is released by positive feedback mechanism., , Action on uterus, Oxytocin acts on pregnant uterus and also non-pregnant, uterus., On pregnant uterus, Throughout the period of pregnancy, oxytocin secretion, is inhibited by estrogen and progesterone. At the end, of pregnancy, the secretion of these two hormones, decreases suddenly and the secretion of oxytocin, increases. Oxytocin causes contraction of uterus and, helps in the expulsion of fetus., During the later stages of pregnancy, the number of, receptors for oxytocin increases in the wall of the uterus., Because of this, the uterus becomes more sensitive to, oxytocin., Oxytocin secretion increases during labor. At the, onset of labor, the cervix dilates and the fetus descends, through the birth canal. During the movement of fetus, through cervix, the receptors on the cervix are stimulated, and start discharging large number of impulses. These, impulses are carried to the paraventricular and supraoptic, nuclei of hypothalamus by the somatic afferent nerve, fibers. Now, these two hypothalamic nuclei secrete large, quantity of oxytocin, which enhances labor by causing, contraction of uterus (Chapter 84)., Throughout labor, large quantity of oxytocin is, released by means of positive feedback mechanism,, i.e. oxytocin induces contraction of uterus, which in turn, causes release of more amount of oxytocin (Fig. 4.5)., The contraction of uterus during labor is also a, neuroendocrine reflex. Oxytocin also stimulates the, release of prostaglandins in the placenta. Prostaglandins, intensify the uterine contraction induced by oxytocin., On non-pregnant uterus, , FIGURE 66.5: Milk ejection reflex, , The action of oxytocin on non-pregnant uterus is to, facilitate the transport of sperms through female genital, tract up to the fallopian tube, by producing the uterine, contraction during sexual intercourse., During the sexual intercourse, the receptors in the, vagina are stimulated. Vaginal receptors generate the, impulses, which are transmitted by somatic afferent, nerves to the paraventricular and supraoptic nuclei of, hypothalamus. When, these two nuclei are stimulated,, oxytocin is released and transported by blood. While, reaching the female genital tract, the hormone causes, antiperistaltic contractions of uterus towards the fallopian, tube. It is also a neuroendocrine reflex., Sensitivity of uterus to oxytocin is accelerated by, estrogen and decreased by progesterone.
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384 Section 6 t Endocrinology, Action in Males, In males, the release of oxytocin increases during, ejaculation. It facilitates release of sperm into urethra, by causing contraction of smooth muscle fibers in, reproductive tract, particularly vas deferens., Mode of Action of Oxytocin, Oxytocin acts on mammary glands and uterus by, activating G-protein coupled oxytocin receptor., , iv. Pituitary tumor also causes visual disturbances., It compresses the lateral fibers of optic chiasma,, leading to bitemporal hemianopia (Chapter, 168), 2. Acromegaly, Acromegaly is the disorder characterized by the, enlargement, thickening and broadening of bones,, particularly in the extremities of the body., Causes, , APPLIED PHYSIOLOGY – DISORDERS, OF PITUITARY GLAND, , Acromegaly is due to hypersecretion of GH in adults, after the fusion of epiphysis with shaft of the bone., Hypersecretion of GH is because of tumor of acidophil, cells in the anterior pituitary., , Disorders of pituitary gland are given in Table 66.1., HYPERACTIVITY OF ANTERIOR PITUITARY, , Signs and symptoms, , 1. Gigantism, Gigantism is the pituitary disorder characterized by, excess growth of the body. The subjects look like the, giants with average height of about 7 to 8 feet., Causes, Gigantism is due to hypersecretion of GH in childhood, or in pre-adult life before the fusion of epiphysis of bone, with shaft. Hypersecretion of GH is because of tumor of, acidophil cells in the anterior pituitary., Signs and symptoms, i. General overgrowth of the person leads to, the development of a huge stature, with a, height of more than 7 or 8 feet. The limbs are, disproportionately long, ii. Giants are hyperglycemic and they develop, glycosuria and pituitary diabetes. Hyperglycemia, causes constant stimulation of β-cells of islets, of Langerhans in the pancreas and release of, insulin. However, the overactivity of β-cells of, Langerhans in pancreas leads to degeneration, of these cells and deficiency of insulin and, ultimately, diabetes mellitus is developed, iii. Tumor of the pituitary gland itself causes, constant headache, , i. Acromegalic or gorilla face: Face with rough, features such as protrusion of supraorbital, ridges, broadening of nose, thickening of lips,, thickening and wrinkles formation on forehead, and prognathism (protrusion of lower jaw) (Fig., 66.6), ii. Enlargement of hands and feet (Fig. 66.7), iii. Kyphosis (extreme curvature of upper back –, thoracic spine), iv. Thickening of scalp. Scalp is also thrown into, folds or wrinkles like bulldog scalp, v. Overgrowth of body hair, vi. Enlargement of visceral organs such as lungs,, thymus, heart, liver and spleen, vii. Hyperactivity of thyroid, parathyroid and adrenal, glands, viii. Hyperglycemia and glucosuria, resulting in, diabetes mellitus, ix. Hypertension, x. Headache, xi. Visual disturbance (bitemporal hemianopia)., 3. Acromegalic Gigantism, Acromegalic gigantism is a rare disorder with symptoms, of both gigantism and acromegaly. Hypersecretion of GH, , TABLE 66.1: Disorders of pituitary gland, Parts involved, , Hyperactivity, , Hypoactivity, , Anterior pituitary, , Gigantism, Acromegaly, Acromegalic gigantism, Cushing disease, , Posterior pituitary, , Syndrome of inappropriate hypersecretion of ADH (SIADH), , Diabetes insipidus, , Anterior and posterior pituitary, , –, , Dystrophia adiposogenitalis, , Dwarfism, Acromicria, Simmond disease
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Chapter 66 t Pituitary Gland 385, , FIGURE 66.6: Acromegaly (Courtesy: Prof Mafauzy Mohamad), , Usually, the disorder due to the pituitary cause is, called Cushing disease and when it is due to the adrenal, cause, it is called Cushing syndrome., Details of this condition are given in Chapter 70., HYPOACTIVITY OF ANTERIOR PITUITARY, 1. Dwarfism, Dwarfism is a pituitary disorder in children, characterized, by the stunted growth., Causes, FIGURE 66.7: A. Normal hand; B. Acromegalic hand, (Courtesy: Prof Mafauzy Mohamad), , in children, before the fusion of epiphysis with shaft of, the bones causes gigantism and if hypersecretion of, GH is continued even after the fusion of epiphysis, the, symptoms of acromegaly also appear., 4. Cushing Disease, It is also a rare disease characterized by obesity., Causes, Cushing disease develops by basophilic adenoma of, adenohypophysis. It increases the secretion of adrenocorticotropic hormone, which in turn stimulates the, adrenal cortex to release cortisol. Cushing disease also, develops by hyperplasia or tumor of adrenal cortex., , Reduction in GH secretion in infancy or early childhood, causes dwarfism. It occurs because of the following, reasons:, i. Tumor of chromophobes: It is a non-functioning, tumor, which compresses and destroys the normal, cells secreting GH. It is the most common cause, for hyposecretion of GH, leading to dwarfism, ii. Deficiency of GH-releasing hormone secreted, by hypothalamus, iii. Deficiency of somatomedin C, iv. Atrophy or degeneration of acidophilic cells in, the anterior pituitary, iv. Panhypopituitarism: In this condition, there is, reduction in the secretion of all the hormones, of anterior pituitary gland. This type of dwarfism, is associated with other symptoms due to the, deficiency of other anterior pituitary hormones.
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386 Section 6 t Endocrinology, Signs and symptoms, i. Primary symptom of hypopituitarism in children, is the stunted skeletal growth. The maximum, height of anterior pituitary dwarf at the adult age, is only about 3 feet, ii. But the proportions of different parts of the body, are almost normal. Only the head becomes, slightly larger in relation to the body, iii. Pituitary dwarfs do not show any deformity and, their mental activity is normal with no mental, retardation, iv. Reproductive function is not affected, if there is, only GH deficiency. However, during panhypopituitarism, the dwarfs do not obtain puberty due, to the deficiency of gonadotropic hormones., Laron dwarfism, Laron dwarfism is a genetic disorder. It is also called GH, insensitivity. It occurs due to the presence of abnormal, growth hormone secretagogue (GHS) receptors in, liver. GHS receptors become abnormal because of the, mutation of genes for the receptors., GH secretion is normal or high. But the hormone, cannot stimulate growth because of the abnormal GHS, receptors. So, dwarfism occurs., Psychogenic dwarfism, Dwarfism occurs if the child is exposed to extreme, emotional deprivation or stress. The short stature is, because of deficiency of GH. This type of dwarfism is, called psychogenic dwarfism, psychosocial dwarfism, or stress dwarfism., Dwarfism in dystrophia adiposogenitalis, Dystrophia adiposogenitalis or Fröhlich syndrome is, a pituitary disorder (see below). Dwarfism occurs if it, develops in children., Dwarfism in panhypopituitarism, Panhypopituitarism is the pituitary disorder due to, reduction in secretion of all anterior pituitary hormones., These dwarfs do not attain puberty., 2. Acromicria, Acromicria is a rare disease in adults characterized by, the atrophy of the extremities of the body., Causes, Deficiency of GH in adults causes acromicria. The, secretion of GH decreases in the following conditions:, i. Deficiency of GH-releasing hormone from, hypothalamus, , ii. Atrophy or degeneration of acidophilic cells in, the anterior pituitary, iii. Tumor of chromophobes: It is a non-functioning, tumor, which compresses and destroys the, normal cells secreting the GH. This is the most, common cause for hyposecretion of GH leading, to acromicria, iv. Panhypopituitarism: In this condition, there is, a reduction in secretion of all the hormones of, anterior pituitary gland. Acromicria is associated, with other symptoms due to the deficiency of, other anterior pituitary hormones., Signs and symptoms, i. Atrophy and thinning of extremities of the body,, (hands and feet) are the major symptoms in, acromicria, ii. Acromicria, is, mostly, associated, with, hypothyroidism, iii. Hyposecretion of adrenocortical hormones also, is common in acromicria, iv. The person becomes lethargic and obese, v. There is loss of sexual functions., 3. Simmond Disease, Simmond disease is a rare pituitary disease. It is also, called pituitary cachexia., Causes, It occurs mostly in panhypopituitarism, i.e. hyposecretion, of all the anterior pituitary hormones due to the atrophy, or degeneration of anterior pituitary., Symptoms, i. A major feature of Simmond disease is the, rapidly developing senile decay. Thus, a 30years-old person looks like a 60-years-old, person. The senile decay is mainly due to, deficiency of hormones from target glands of, anterior pituitary, i.e. the thyroid gland, adrenal, cortex and the gonads, ii. There is loss of hair over the body and loss of, teeth, iii. Skin on face becomes dry and wrinkled. So, there, is a shrunken appearance of facial features. It is, the most common feature of this disease., HYPERACTIVITY OF POSTERIOR PITUITARY, Syndrome of Inappropriate Hypersecretion, of Antidiuretic Hormone (SIADH), SIADH is the disease characterized by loss of sodium, through urine due to hypersecretion of ADH.
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Chapter 66 t Pituitary Gland 387, Causes, SIADH occurs due to cerebral tumors, lung tumors and, lung cancers because the tumor cells and cancer cells, secrete ADH., In normal conditions, ADH decreases the urine, output by facultative reabsorption of water in distal, convoluted tubule and the collecting duct. Urine that is, formed is concentrated with sodium and other ions. Loss, of sodium decreases the osmalarity of plasma, making, it hypotonic. Hypotonic plasma inhibits ADH secretion, resulting in restoration of plasma osmolarity., However, in SIADH, secretion of ADH from tumor, or cancer cells is not inhibited by hypotonic plasma. So, there is continuous loss of sodium, resulting in persistent, plasma hypotonicity., Signs and symptoms, 1., 2., 3., 4., 5., 6., 7., , Loss of appetite, Weight loss, Nausea and vomiting, Headache, Muscle weakness, spasm and cramps, Fatigue, Restlessness and irritability., In severe conditions, the patients die because of, convulsions and coma., HYPOACTIVITY OF POSTERIOR PITUITARY, Diabetes Insipidus, Diabetes insipidus is a posterior pituitary disorder, characterized by excess excretion of water through, urine., Causes, This disorder develops due to the deficiency of ADH,, which occurs in the following conditions:, i. Lesion (injury) or degeneration of supraoptic, and paraventricular nuclei of hypothalamus, ii. Lesion in hypothalamo-hypophyseal tract, iii. Atrophy of posterior pituitary, iv. Inability of renal tubules to give response to ADH, hormone. Such condition is called nephrogenic, diabetes insipidus (see below)., Signs and symptoms, i. Polyuria: Excretion of large quantity of dilute, urine, with increased frequency of voiding is, called polyuria. Daily output of urine varies, between 4 to 12 liter. In the absence of ADH, the, epithelial cells of distal convoluted tubule in the, nephron and the collecting duct of the kidney, become impermeable to water. So, water is not, , reabsorbed from the renal tubule and collecting, duct, leading to loss of water through urine., ii. Polydipsia: Intake of excess water is called, polydipsia. Because of polyuria, lot of water is, lost from the body. It stimulates the thirst center, in hypothalamus, resulting in intake of large, quantity of water., iii. Dehydration: In some cases, the thirst center in, the hypothalamus is also affected by the lesion., Water intake decreases in these patients and, loss of water through urine is not compensated., So, dehydration develops which may lead to, death., Nephrogenic diabetes insipidus, Nephrogenic diabetes insipidus is a genetic disorder, due to inability of renal tubules to give response to ADH., It is caused by mutations of genes of V2 receptors or, aquaporin 2., HYPOACTIVITY OF ANTERIOR, AND POSTERIOR PITUITARY, Dystrophia Adiposogenitalis, Dystrophia adiposogenitalis is a disease characterized, by obesity and hypogonadism, affecting mainly the, adolescent boys. It is also called Fröhlich syndrome or, hypothalamic eunuchism., , Causes, Dystrophia adiposogenitalis is due to hypoactivity of, both anterior pituitary and posterior pituitary. Common, cause of this disease is the tumor in pituitary gland and, hypothalamic regions, concerned with food intake and, gonadal development. Other causes are injury or atrophy, of pituitary gland and genetic inability of hypothalamus, to secrete luteinizing hormone-releasing hormone., Symptoms, Obesity is the common feature of this disorder. Due to, the abnormal stimulation of feeding center, the person, overeats and consequently becomes obese. Obesity is, accompanied by sexual infantilism (failure to develop, secondary sexual characters) or eunuchism. Dwarfism, occurs if the disease starts in growing age. In children,, it is called infantile or prepubertal type of Fröhlich, syndrome., This disease develops in adults also. When it occurs, in adults, it is called adult type of Fröhlich syndrome. In, adults, the major symptoms are obesity and atrophy of, sex organs., Other features of this disorder are behavioral, changes and loss of vision. Some patients develop, diabetes insipidus.
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Thyroid Gland, , , , , , , , , , , , , , Chapter, , 67, , INTRODUCTION, HISTOLOGY OF THYROID GLAND, HORMONES OF THYROID GLAND, SYNTHESIS OF THYROID HORMONES, STORAGE OF THYROID HORMONES, RELEASE OF THYROID HORMONES, TRANSPORT OF THYROID HORMONES IN THE BLOOD, FUNCTIONS OF THYROID HORMONES, MODE OF ACTION OF THYROID HORMONES, APPLIED PHYSIOLOGY – DISORDERS OF THYROID GLAND, TREATMENT FOR THYROID DISORDERS, THYROID FUNCTION TESTS, , INTRODUCTION, Thyroid is an endocrine gland situated at the root of, the neck on either side of the trachea. It has two lobes,, which are connected in the middle by an isthmus (Fig., 67.1). It weighs about 20 to 40 g in adults. Thyroid is, larger in females than in males. The structure and the, function of the thyroid gland change in different stages, , of the sexual cycle in females. Its function increases, slightly during pregnancy and lactation and decreases, during menopause., , HISTOLOGY OF THYROID GLAND, Thyroid gland is composed of large number of closed, follicles. These follicles are lined with cuboidal epithelial, cells, which are called the follicular cells. Follicular, cavity is filled with a colloidal substance known as, thyroglobulin, which is secreted by the follicular cells., Follicular cells also secrete tetraiodothyronine (T4 or, thyroxine) and tri-iodothyronine (T3). In between the, follicles, the parafollicular cells are present (Fig. 67.2)., These cells secrete calcitonin., , HORMONES OF THYROID GLAND, , FIGURE 67.1: Thyroid gland, , Thyroid gland secretes three hormones:, 1. Tetraiodothyronine or T4 (thyroxine), 2. Tri-iodothyronine or T3, 3. Calcitonin., T4 is otherwise known as thyroxine and it forms, about 90% of the total secretion, whereas T3 is only 9%, to 10%. Details of calcitonin are given in next chapter.
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Chapter 67 t Thyroid Gland 389, , SYNTHESIS OF THYROID HORMONES, Synthesis of thyroid hormones takes place in thyroglobulin, present in follicular cavity. Iodine and tyrosine are, essential for the formation of thyroid hormones. Iodine, is consumed through diet. It is converted into iodide, and absorbed from GI tract. Tyrosine is also consumed, through diet and is absorbed from the GI tract., For the synthesis of normal quantities of thyroid, hormones, approximately 1 mg of iodine is required, per week or about 50 mg per year. To prevent iodine, deficiency, common table salt is iodized with one part, of sodium iodide to every 100,000 parts of sodium, chloride., FIGURE 67.2: Histology of thyroid gland, , STAGES OF SYNTHESIS OF, THYROID HORMONES, , Chemistry, Both T4 and T3 are iodine-containing derivatives of, amino acid tyrosine., Potency and Duration of Action, The potency of T3 is four times more than that of T4. T4, acts for longer period than T3. Duration of T4 action is, four times more than T3 action. This is because of the, difference in the affinity of these hormones to plasma, proteins. T3 has less affinity for plasma proteins and, combines loosely with them, so that it is released quickly., T4 has more affinity and strongly binds with plasma, proteins, so that it is released slowly. Therefore, T3 acts, on the target cells immediately and T4 acts slowly., , Synthesis of thyroid hormones occurs in five stages:, 1. Thyroglobulin synthesis, 2. Iodide trapping, 3. Oxidation of iodide, 4. Transport of iodine into follicular cavity, 5. Iodination of tyrosine, 6. Coupling reactions., 1. Thyroglobulin Synthesis, Endoplasmic reticulum and Golgi apparatus in the, follicular cells of thyroid gland synthesize and secrete, thyroglobulin continuously. Thyroglobulin molecule is a, large glycoprotein containing 140 molecules of amino, acid tyrosine. After synthesis, thyroglobulin is stored in, the follicle., , Half-life, Thyroid hormones have long half-life. T4 has a long halflife of 7 days. Half-life of T3 is varying between 10 and, 24 hours., Rate of Secretion, Thyroxine, = 80 to 90 µg/day, Tri-iodothyronine = 4 to 5 µg/day, Reverse T3, = 1 to 2 µg/day., , 2. Iodide Trapping, Iodide is actively transported from blood into follicular, cell, against electrochemical gradient. This process is, called iodide trapping., Iodide is transported into the follicular cell along with, sodium by sodium-iodide symport pump, which is also, called iodide pump. Normally, iodide is 30 times more, concentrated in the thyroid gland than in the blood., However, during hyperactivity of the thyroid gland, the, concentration of iodide increases 200 times more., , Plasma Level, Total T3, Total T4, , = 0.12 µg/dL, =, 8 µg/dL., , Metabolism of Thyroid Hormones, Degradation of thyroid hormones occurs in muscles,, liver and kidney., , 3. Oxidation of Iodide, Iodide must be oxidized to elementary iodine, because, only iodine is capable of combining with tyrosine to form, thyroid hormones. The oxidation of iodide into iodine, occurs inside the follicular cells in the presence of, thyroid peroxidase. Absence or inactivity of this enzyme, stops the synthesis of thyroid hormones.
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390 Section 6 t Endocrinology, 4. Transport of Iodine into Follicular Cavity, From the follicular cells, iodine is transported into the, follicular cavity by an iodide-chloride pump called, pendrin., , 5. Iodination of Tyrosine, Combination of iodine with tyrosine is known as, iodination. It takes place in thyroglobulin. First, iodine is, transported from follicular cells into the follicular cavity,, where it binds with thyroglobulin. This process is called, organification of thyroglobulin. Then, iodine (I) combines, with tyrosine, which is already present in thyroglobulin, (Fig. 67.3). Iodination process is accelerated by the, enzyme iodinase, which is secreted by follicular cells., Iodination of tyrosine occurs in several stages., Tyrosine is iodized first into monoiodotyrosine (MIT) and, later into di-iodotyrosine (DIT). MIT and DIT are called, the iodotyrosine residues., 6. Coupling Reactions, Iodotyrosine residues get coupled with one another. The, coupling occurs in different configurations, to give rise to, different thyroid hormones., Coupling reactions are:, i. One molecule of DIT and one molecule of MIT, combine to form tri-iodothyronine (T3), , ii. Sometimes one molecule of MIT and one, molecule of DIT combine to produce another, form of T3 called reverse T3 or rT3. Reverse T3 is, only 1% of thyroid output, iii. Two molecules of DIT combine to form tetraiodothyronine (T4), which is thyroxine., Tyrosine + I =, MIT + I, =, DIT + MIT =, MIT + DIT =, DIT + DIT =, , Monoiodotyrosine (MIT), Di-iodotyrosine (DIT), Tri-iodothyronine (T3), Reverse T3, Tetraiodothyronine or Thyroxine (T4), , STORAGE OF THYROID HORMONES, After synthesis, the thyroid hormones remain in the, form of vesicles within thyroglobulin and are stored for, long period. Each thyroglobulin molecule contains 5 or, 6 molecules of thyroxine. There is also an average of, 1 tri-iodothyronine molecule for every 10 molecules of, thyroxine., In combination with thyroglobulin, the thyroid, hormones can be stored for several months. Thyroid, gland is unique in this, as it is the only endocrine gland, that can store its hormones for a long period of about, 4 months. So, when the synthesis of thyroid hormone, stops, the signs and symptoms of deficiency do not, appear for about 4 months., , FIGURE 67.3: Synthesis of thyroid hormones
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Chapter 67 t Thyroid Gland 391, , RELEASE OF THYROID HORMONES, FROM THE THYROID GLAND, Thyroglobulin itself is not released into the bloodstream., On the other hand, the hormones are first cleaved from, thyroglobulin and released into the blood., Sequence of Events, 1. Follicular cell sends foot-like extensions called, pseudopods, which close around the thyroglobulinhormone complex. This process is mediated by a, receptor-like substance called megalin, which is, present in the membrane of follicular cell, 2. Pseudopods convert thyroglobulin-hormone complex into small pinocytic vesicles, 3. Then, lysosomes of the cell fuse with these, vesicles, 4. Digestive enzymes such as proteinases present, in lysosomes digest (proteolysis) the thyroglobulin, and release the hormones, 5. Now, the hormones diffuse through base of the, follicular cell and enter the capillaries., Only T3 and T4 are released into the blood. In the, peripheral tissues, T4 is converted into T3. A small, amount of inactive reverse T3 is also formed. It is the, biologically inactive form of T3 and it is produced when, T4 is converted into T3., MIT and DIT are not released into blood. These, iodotyrosine residues are deiodinated by an enzyme, called iodotyrosine deiodinase, resulting in the release, of iodine. The iodine is reutilized by the follicular cells for, further synthesis of thyroid hormones. During congenital, absence of iodotyrosine deiodinase, MIT and DIT are, excreted in urine and the symptoms of iodine deficiency, develop., , TRANSPORT OF THYROID, HORMONES IN THE BLOOD, Thyroid hormones are transported in the blood by three, types of proteins:, 1. Thyroxine-binding globulin (TBG), 2. Thyroxine-binding prealbumin (TBPA), 3. Albumin., 1. Thyroxine-binding Globulin (TBG), Thyroxine-binding globulin is a glycoprotein and its, concentration in the blood is 1 to 1.5 mg/dL. It has a, great affinity for thyroxine and about one third of the, hormone combines strongly with this protein., , 2. Thyroxine-binding Prealbumin (TBPA), TBPA transports one fourth of the thyroid hormones. It is, also called transthyretin (TTR)., 3. Albumin, Albumin transports about one tenth of the thyroid, hormones., , FUNCTIONS OF THYROID HORMONES, Thyroid hormones have two major effects on the body:, I. To increase basal metabolic rate, II. To stimulate growth in children., The actions of thyroid hormones are:, 1. ACTION ON BASAL METABOLIC RATE (BMR), Thyroxine increases the metabolic activities in most of, the body tissues, except brain, retina, spleen, testes, and lungs. It increases BMR by increasing the oxygen, consumption of the tissues. The action that increases, the BMR is called calorigenic action., In hyperthyroidism, BMR increases by about 60%, to 100% above the normal level and in hypothyroidism it, falls by 20% to 40% below the normal level., 2. ACTION ON PROTEIN METABOLISM, Thyroid hormone increases the synthesis of proteins in, the cells. The protein synthesis is accelerated by the, following ways:, i. By Increasing the Translation of RNA, Thyroid hormone increases the translation of RNA in the, cells. Because of this, the ribosomes are activated and, more proteins are synthesized., ii. By Increasing the Transcription of DNA to RNA, Thyroid hormone also stimulates the transcription of, DNA to RNA. This in turn accelerates the synthesis of, proteins in the cells (see above)., iii. By Increasing the Activity of Mitochondria, In addition to acting at nucleus, thyroid hormone acts, at mitochondrial level also. It increases the number, and the activity of mitochondria in most of the cells of, the body. Thyroid hormone accelerates the synthesis, of RNA and other substances from mitochondria, by, activating series of enzymes. In turn, the mitochondria, increase the production of ATP, which is utilized for the, energy required for cellular activities.
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392 Section 6 t Endocrinology, iv. By Increasing the Activity of Cellular Enzymes, Thyroid hormones also increase the activity of at least, 100 or more intracellular enzymes such as alphaglycerophosphate dehydrogenase and oxidative, enzymes. These enzymes accelerate the metabolism of, proteins and the carbohydrates., Though thyroxine increases synthesis of protein, it, also causes catabolism of proteins., 3. ACTION ON CARBOHYDRATE METABOLISM, Thyroxine stimulates almost all processes involved in, the metabolism of carbohydrate., Thyroxine:, i. Increases the absorption of glucose from GI, tract, ii. Enhances the glucose uptake by the cells, by, accelerating the transport of glucose through, the cell membrane, iii. Increases the breakdown of glycogen into, glucose, iv. Accelerates gluconeogenesis., 4. ACTION ON FAT METABOLISM, Thyroxine decreases the fat storage by mobilizing it, from adipose tissues and fat depots. The mobilized, fat is converted into free fatty acid and transported by, blood. Thus, thyroxine increases the free fatty acid level, in blood., 5. ACTION ON PLASMA AND LIVER FATS, Even though there is an increase in the blood level of, free fatty acids, thyroxine specifically decreases the, cholesterol, phospholipids and triglyceride levels in, plasma. So, in hyposecretion of thyroxine, the cholesterol, level in plasma increases, resulting in atherosclerosis., Thyroxine also increases deposition of fats in the, liver, leading to fatty liver. Thyroxine decreases plasma, cholesterol level by increasing its excretion from liver, cells into bile. Cholesterol enters the intestine through, bile and then it is excreted through the feces., 6. ACTION ON VITAMIN METABOLISM, Thyroxine increases the formation of many enzymes., Since vitamins form essential parts of the enzymes, it, is believed that the vitamins may be utilized during the, formation of the enzymes. Hence, vitamin deficiency is, possible during hypersecretion of thyroxine., 7. ACTION ON BODY TEMPERATURE, Thyroid hormone increases the heat production in the, body, by accelerating various cellular metabolic processes, , and increasing BMR. It is called thyroid hormoneinduced thermogenesis. During hypersecretion of, thyroxine, the body temperature increases greatly,, resulting in excess sweating., 8. ACTION ON GROWTH, Thyroid hormones have general and specific effects on, growth. Increase in thyroxine secretion accelerates the, growth of the body, especially in growing children. Lack of, thyroxine arrests the growth. At the same time, thyroxine, causes early closure of epiphysis. So, the height of the, individual may be slightly less in hypothyroidism., Thyroxine is more important to promote growth and, development of brain during fetal life and first few years, of postnatal life. Deficiency of thyroid hormones during, this period leads to mental retardation., 9. ACTION ON BODY WEIGHT, Thyroxine is essential for maintaining the body weight., Increase in thyroxine secretion decreases the body, weight and fat storage. Decrease in thyroxine secretion, increases the body weight because of fat deposition., 10. ACTION ON BLOOD, Thyroxine accelerates erythropoietic activity and, increases blood volume. It is one of the important general, factors necessary for erythropoiesis. Polycythemia is, common in hyperthyroidism., 11. ACTION ON CARDIOVASCULAR SYSTEM, Thyroxine increases the overall activity of cardiovascular, system., i. On Heart Rate, Thyroxine acts directly on heart and increases the, heart rate. It is an important clinical investigation for, diagnosis of hypothyroidism and hyperthyroidism., ii. On the Force of Contraction of the Heart, Due to its effect on enzymatic activity, thyroxine, generally increases the force of contraction of the, heart. But in hyperthyroidism or in thyrotoxicosis, the, heart may become weak due to excess activity and, protein catabolism. So, the patient may die of cardiac, decompensation., , Cardiac decompensation refers to failure of the, heart to maintain adequate circulation associated with, dyspnea, venous engorgement (veins overfilled with, blood) and edema.
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Chapter 67 t Thyroid Gland 393, iii. On Blood Vessels, Thyroxine causes vasodilatation by increasing the, metabolic activities. During increased metabolic, activities, a large quantity of metabolites is produced., These metabolites cause vasodilatation., , psychoneurotic problems such as anxiety complexes,, excess worries or paranoid thoughts (the persons, think without justification that other people are plotting, or conspiring against them or harassing them)., Hyposecretion of thyroxine leads to lethargy and, somnolence (excess sleep)., , iv. On Arterial Blood Pressure, , 15. ACTION ON SKELETAL MUSCLE, , Because of increase in rate and force of contraction of, the heart, increase in blood volume and blood flow by, the influence of thyroxine, cardiac output increases. This, in turn, increases the blood pressure. But, generally,, the mean pressure is not altered. Systolic pressure, increases and the diastolic pressure decreases. So,, only the pulse pressure increases (Chapter 103)., , Thyroxine is essential for the normal activity of skeletal, muscles. Slight increase in thyroxine level makes the, muscles to work with more vigor. But, hypersecretion, of thyroxine causes weakness of the muscles due to, catabolism of proteins. This condition is called thyrotoxic, myopathy. The muscles relax very slowly after the, contraction. Hyperthyroidism also causes fine muscular, tremor. Tremor occurs at the frequency of 10 to 15 times, per second. It is due to the thyroxine-induced excess, neuronal activity, which controls the muscle. The lack of, thyroxine makes the muscles more sluggish., , 12. ACTION ON RESPIRATION, Thyroxine increases the rate and force of respiration, indirectly. The increased metabolic rate (caused by, thyroxine) increases the demand for oxygen and, formation of excess carbon dioxide. These two factors, stimulate the respiratory centers to increase the rate, and force of respiration (Chapter 126)., 13. ACTION ON GASTROINTESTINAL TRACT, Generally, thyroxine increases the appetite and food, intake. It also increases the secretions and movements, of GI tract. So, hypersecretion of thyroxine causes, diarrhea and the lack of thyroxine causes constipation., , 16. ACTION ON SLEEP, Normal thyroxine level is necessary to maintain normal, sleep pattern. Hypersecretion of thyroxine causes, excessive stimulation of the muscles and central nervous, system. So, the person feels tired, exhausted and feels, like sleeping. But, the person cannot sleep because, of the stimulatory effect of thyroxine on neurons. On, the other hand, hyposecretion of thyroxine causes, somnolence., , 14. ACTION ON CENTRAL NERVOUS SYSTEM, , 17. ACTION ON SEXUAL FUNCTION, , Thyroxine is very essential for the development and, maintenance of normal functioning of central nervous, system (CNS)., , Normal thyroxine level is essential for normal sexual, function. In men, hypothyroidism leads to complete loss, of libido (sexual drive) and hyperthyroidism leads to, impotence., , i. On Development of Central Nervous System, Thyroxine is very important to promote growth and, development of the brain during fetal life and during, the first few years of postnatal life. Thyroid deficiency, in infants results in abnormal development of synapses,, defective myelination and mental retardation., ii. On the Normal Function of Central, Nervous System, Thyroxine is a stimulating factor for the central nervous, system, particularly the brain. So, the normal functioning, of the brain needs the presence of thyroxine. Thyroxine, also increases the blood flow to brain., Thus, during the hypersecretion of thyroxine, there, is excess stimulation of the CNS. So, the person is, likely to have extreme nervousness and may develop, , In women, hypothyroidism causes menorrhagia and, polymenorrhea (Chapter 80). In some women, it causes, irregular menstruation and occasionally amenorrhea., Hyperthyroidism in women leads to oligomenorrhea, and sometimes amenorrhea (Chapter 80)., , 18. ACTION ON OTHER ENDOCRINE GLANDS, Because of its metabolic effects, thyroxine increases, the demand for secretion by other endocrine glands., , MODE OF ACTION OF, THYROID HORMONES, In the target cells (particularly cells of liver, muscle and, kidney), most of the T4 is deiodinated to form T3. So, the, true intracellular hormone is T3, rather than T4. Moreover,, T3 is found freely in the plasma and T4 is usually bound
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394 Section 6 t Endocrinology, with plasma proteins. So, at the site of action, T3 acts, more quickly than T4. T3 also has got high binding affinity, for thyroid hormone receptor., Thyroid hormones act by activating the genes and, increasing the genetic transcription (Chapter 65). In, addition, the thyroid hormone also acts at mitochondrial, level by stimulating the synthesis of proteins and RNA., Sequence of Events, 1. Thyroid hormones enter the nucleus of cell and, bind with thyroid hormone receptors (TR), which are, either attached to DNA genetic strands or in close, proximity to them., 2. TR is always bound to another receptor called, retinoid X receptor (RXR). Exact role of RXR is not, clear. Thyroid hormones bind with receptors and, form the hormone-receptor complex, 3. This complex initiates the transcription process by, activating the enzymes such as RNA polymerase, and phosphoprotein kinases, 4. It also stimulates the synthesis of nuclear proteins., Thus, a large number of mRNA is formed, which, activate the ribosomes to synthesize the new, proteins, 5. New proteins are involved in many activities, including the enzymatic actions., , REGULATION OF SECRETION, OF THYROID HORMONES, Secretion of thyroid hormones is controlled by, anterior pituitary and hypothalamus through feedback, mechanism. Many factors are involved in the regulation, of thyroid secretion., ROLE OF PITUITARY GLAND, Thyroid-stimulating Hormone, Thyroid-stimulating hormone (TSH) secreted by anterior, pituitary is the major factor regulating the synthesis and, release of thyroid hormones. It is also necessary for the, growth and the secretory activity of the thyroid gland., Thus, TSH influences every stage of formation and, release of thyroid hormones., Chemistry, Thyroid-stimulating hormone is a peptide hormone with, one α-chain and one β-chain., Half-life and Plasma Level, Half-life of TSH is about 60 minutes. The normal plasma, level of TSH is approximately 2 U/mL., , Actions of Thyroid-stimulating Hormone, Thyroid-stimulating hormone increases:, 1. The number of follicular cells of thyroid, 2. The conversion of cuboidal cells in thyroid gland, into columnar cells and thereby it causes the, development of thyroid follicles, 3. Size and secretory activity of follicular cells, 4. Iodide pump and iodide trapping in follicular cells, 5. Thyroglobulin secretion into follicles, 6. Iodination of tyrosine and coupling to form the, hormones, 7. Proteolysis of the thyroglobulin, by which release, of hormone is enhanced and colloidal substance is, decreased., Immediate effect of TSH is proteolysis of the, thyroglobulin, by which thyroxine is released within 30, minutes. Effect of TSH on other stages in thyroxine, synthesis takes place after some hours, days or, weeks., Mode of Action of TSH, TSH acts through cyclic AMP mechanism., ROLE OF HYPOTHALAMUS, Hypothalamus regulates thyroid secretion by controlling, TSH secretion through thyrotropic-releasing hormone, (TRH). From hypothalamus, TRH is transported through, the hypothalamo-hypophyseal portal vessels to the, anterior pituitary. After reaching the pituitary gland, the, TRH causes the release of TSH., FEEDBACK CONTROL, Thyroid hormones regulate their own secretion through, negative feedback control, by inhibiting the release of, TRH from hypothalamus and TSH from anterior pituitary, (Fig. 67.4)., ROLE OF IODIDE, Iodide is an important factor regulating the synthesis, of thyroid hormones. When the dietary level of iodine, is moderate, the blood level of thyroid hormones is, normal. However, when iodine intake is high, the, enzymes necessary for synthesis of thyroid hormones, are inhibited by iodide itself, resulting in suppression of, hormone synthesis. This effect of iodide is called WolffChaikoff effect., , ROLE OF OTHER FACTORS, Many other factors are involved in the regulation of, thyroid secretion in accordance to the needs of the, body.
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Chapter 67 t Thyroid Gland 395, Causes of Hyperthyroidism, Hyperthyroidism is caused by:, 1. Graves’ disease, 2. Thyroid adenoma., 1. Graves’ disease, Graves’ disease is an autoimmune disease and it is, the most common cause of hyperthyroidism. Normally,, TSH combines with surface receptors of thyroid cells, and causes the synthesis and secretion of thyroid, hormones. In Graves’ disease, the B lymphocytes, (plasma cells) produce autoimmune antibodies called, thyroid-stimulating autoantibodies (TSAbs). These, antibodies act like TSH by binding with membrane, receptors of TSH and activating cAMP system of the, thyroid follicular cells. This results in hypersecretion of, thyroid hormones., Antibodies act for a long time even up to 12 hours in, contrast to that of TSH, which lasts only for an hour or, so. The high concentration of thyroid hormones caused, by the antibodies suppresses the TSH production also., So, the concentration of TSH is low or almost zero in, plasma of most of the hyperthyroid patients., 2. Thyroid adenoma, FIGURE 67.4: Regulation of secretion of thyroid hormones, , Factors increasing the secretion of thyroid, hormones:, 1. Low basal metabolic rate, 2. Leptin, 3. α-melanocyte-stimulating hormone, Leptin (from adipose tissue) and α-melanocytestimulating hormone (from pituitary) increase the, release of TRH and synthesis of T4. The low body, temperature also stimulates the synthesis of thyroid, hormones. However, this occurs only in infants., Factors decreasing the secretion of thyroid hormones:, 1. Excess iodide intake, 2. Stress, 3. Somatostatin, 4. Glucocorticoids, 5. Dopamine., These factors decrease the secretion of thyroid, hormones, by inhibiting the release of TRH., , APPLIED PHYSIOLOGY –, DISORDERS OF THYROID GLAND, HYPERTHYROIDISM, Increased secretion of thyroid hormones is called, hyperthyroidism., , Sometimes, a localized tumor develops in the thyroid, tissue. It is known as thyroid adenoma and it secretes, large quantities of thyroid hormones. It is not associated, with autoimmunity. As far as this adenoma remains, active, the other parts of thyroid gland cannot secrete, the hormone. This is because, the hormone secreted, from adenoma depresses the production of TSH., Signs and Symptoms of Hyperthyroidism, 1. Intolerance to heat as the body produces lot of heat, due to increased basal metabolic rate caused by, excess of thyroxine, 2. Increased sweating due to vasodilatation, 3. Decreased body weight due to fat mobilization, 4. Diarrhea due to increased motility of GI tract, 5. Muscular weakness because of excess protein, catabolism, 6. Nervousness, extreme fatigue, inability to sleep, mild, tremor in the hands and psychoneurotic symptoms, such as hyperexcitability, extreme anxiety or worry., All these symptoms are due to the excess stimulation, of neurons in the central nervous system, 7. Toxic goiter (see below), 8. Oligomenorrhea or amenorrhea (Chapter 80), 9. Exophthalmos (see below), 10. Polycythemia, 11. Tachycardia and atrial fibrillation
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396 Section 6 t Endocrinology, 12. Systolic hypertension, 13. Cardiac failure., , Myxedema, , 3. Non-pitting type of edema, i.e. when pressed,, it does not make pits and the edema is hard., It is because of accumulation of proteins with, hyaluronic acid and chondroitin sulfate, which, form a hard tissue with increased accumulation, of fluid, 4. Atherosclerosis: It is the hardening of the walls of, arteries because of accumulation of fat deposits, and other substances. In myxedema, it occurs, because of increased plasma level of cholesterol, which leads to deposition of cholesterol on the, walls of the arteries., Atherosclerosis produces arteriosclerosis, which, refers to thickening and stiffening of arterial wall., Arteriosclerosis causes hypertension., Other general features of hypothyroidism in adults, are:, 1. Anemia, 2. Fatigue and muscular sluggishness, 3. Extreme somnolence with sleeping up to 14 to, 16 hours per day, 4. Menorrhagia and polymenorrhea, 5. Decreased cardiovascular functions such as, reduction in rate and force of contraction of the, heart, cardiac output and blood volume, 6. Increase in body weight, 7. Constipation, 8. Mental sluggishness, 9. Depressed hair growth, 10. Scaliness of the skin, 11. Frog-like husky voice, 12. Cold intolerance., , Myxedema is the hypothyroidism in adults, characterized, by generalized edematous appearance., , Cretinism, , Exophthalmos, Protrusion of eye balls is called exophthalmos. Most,, but not all hyperthyroid patients develop some degree, of protrusion of eyeballs., Causes for exophthalmos, Exophthalmos in hyperthyroidism is due to the edematous swelling of retro-orbital tissues and degenerative, changes in the extraocular muscles., Effect of exophthalmos on vision, Severe exophthalmic condition leads to blindness, because of two reasons:, 1. Protrusion of the eyeball, which stretches and, damages the optic nerve, resulting in blindness or, 2. Due to the protrusion of eyeballs, the eyelids, cannot be closed completely while blinking, or during sleep. So, the constant exposure of, eyeball to atmosphere causes dryness of the, cornea, leading to irritation and infection. It, finally results in ulceration of the cornea leading, to blindness., HYPOTHYROIDISM, Decreased secretion of thyroid hormones is called, hypothyroidism. Hypothyroidism leads to myxedema in, adults and cretinism in children., , Causes for myxedema, Myxedema occurs due to diseases of thyroid gland,, genetic disorder or iodine deficiency. In addition, it is also, caused by deficiency of thyroid-stimulating hormone or, thyrotropin-releasing hormone., Common cause of myxedema is the autoimmune, disease called Hashimoto’s thyroiditis, which is, common in late middle-aged women (Chapter 17). In, most of the patients, it starts with glandular inflammation, called thyroiditis caused by autoimmune antibodies., Later it leads to destruction of the glands., Signs and symptoms of myxedema, Typical feature of this disorder is an edematous, appearance throughout the body. It is associated with, the following symptoms:, 1. Swelling of the face, 2. Bagginess under the eyes, , Cretinism is the hypothyroidism in children, characterized, by stunted growth., Causes for cretinism, Cretinism occurs due to congenital absence of thyroid, gland, genetic disorder or lack of iodine in the diet., Features of cretinism, 1. A newborn baby with thyroid deficiency may, appear normal at the time of birth because, thyroxine might have been supplied from mother., But a few weeks after birth, the baby starts, developing the signs like sluggish movements, and croaking sound while crying. Unless treated, immediately, the baby will be mentally retarded, permanently., 2. Skeletal growth is more affected than the soft, tissues. So, there is stunted growth with bloated
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Chapter 67 t Thyroid Gland 397, body. The tongue becomes so big that it hangs, down with dripping of saliva. The big tongue, obstructs swallowing and breathing. The tongue, produces characteristic guttural breathing that, may sometimes choke the baby., Cretin Vs dwarf, A cretin is different from pituitary dwarf. In cretinism,, there is mental retardation and the different parts of, the body are disproportionate. Whereas, in dwarfism,, the development of nervous system is normal and the, parts of the body are proportionate (Fig. 67.5). The, reproductive function is affected in cretinism but it may, be normal in dwarfism., GOITER, Goiter means enlargement of the thyroid gland. It occurs, both in hypothyroidism and hyperthyroidism., Goiter in Hyperthyroidism – Toxic Goiter, Toxic goiter is the enlargement of thyroid gland with, increased secretion of thyroid hormones, caused by, thyroid tumor., Goiter in Hypothyroidism – Non-toxic Goiter, Non-toxic goiter is the enlargement of thyroid gland, without increase in hormone secretion. It is also called, hypothyroid goiter (Fig. 67.6)., Based on the cause, the non-toxic hypothyroid, goiter is classified into two types., 1. Endemic colloid goiter, 2. Idiopathic non-toxic goiter., , FIGURE 67.5: Cretinism (3-month-old baby), (Courtesy: Prof Mafauzy Mohamad), , 1. Endemic colloid goiter, Endemic colloid goiter is the non-toxic goiter caused, by iodine deficiency. It is also called iodine deficiency, goiter. Iodine deficiency occurs when intake is less, than 50 µg/day. Because of lack of iodine, there is, no formation of hormones. By feedback mechanism,, hypothalamus and anterior pituitary are stimulated., It increases the secretion of TRH and TSH. The TSH, then causes the thyroid cells to secrete tremendous, amounts of thyroglobulin into the follicle. As there are, no hormones to be cleaved, the thyroglobulin remains, as it is and gets accumulated in the follicles of the gland., This increases the size of gland., In certain areas of the world, especially in the Swiss, Alps, Andes, Great Lakes region of United States and, in India, particularly in Kashmir Valley, the soil does not, contain enough iodine. Therefore, the foodstuffs also, do not contain iodine. The endemic colloid goiter was, very common in these parts of the world before the, introduction of iodized salts., 2. Idiopathic non-toxic goiter, Idiopathic non-toxic goiter is the goiter due to unknown, cause. Enlargement of thyroid gland occurs even without iodine deficiency. The exact cause is not known. It is, suggested that it may be due to thyroiditis and deficiency, of enzymes such as peroxidase, iodinase and deiodinase, which are required for thyroid hormone synthesis., Some foodstuffs contain goiterogenic substances, (goitrogens) such as goitrin. These substances contain, antithyroid substances like propylthiouracil. Goitrogens, suppress the synthesis of thyroid hormones. Therefore,, TSH secretion increases, resulting in enlargement of, the gland. Such goitrogens are found in vegetables like, turnips and cabbages. Soybean also contains some, amount of goitrogens., , FIGURE 67.6: Non-toxic goiter, (Courtesy: Prof Mafauzy Mohamad)
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398 Section 6 t Endocrinology, , TREATMENT FOR THYROID DISORDERS, , the size of the gland is also reduced with decreased, blood supply. Because of this, iodides are frequently, administered to hyperthyroid patients for 2 or 3 weeks,, prior to surgical removal of the thyroid gland., , TREATMENT FOR HYPERTHYROIDISM, , 2. By Surgical Removal, , The goitrogens become active only during low, iodine intake., , 1. By using Antithyroid Substances, Antithyroid substances are the drugs which suppress, the secretion of thyroid hormones. Hyperthyroidism in, early stage can be treated by antithyroid substances., Three well-known antithyroid substances are:, i. Thiocyanate, ii. Thiourylenes, iii. High concentration of inorganic iodides., i. Thiocyanate, Thiocyanate prevents synthesis of thyroxine by inhibiting, iodide trapping. The active pump which transports iodide, into the thyroid cells, can transport thiocyanate ions also., So, administration of thiocyanate in high concentrations, causes competitive inhibition of iodide transport into, the cell. So, iodide trapping is inhibited, leading to the, inhibition of synthesis of thyroxine., ii. Thiourylenes, Thiourylenes are the thiourea-related substances such, as propylthiouracil and methimazole, which prevent the, formation of thyroid hormone from iodides and tyrosine., It is achieved partly by blocking peroxidase enzyme, activity and partly by blocking coupling of iodinated, tyrosine to form either T3 or T4., During the use of these two antithyroid substances,, even though the synthesis of thyroid hormone is, inhibited, the formation of thyroglobulin is not stopped., The deficiency of the hormone increases the TSH, secretion, which increases the size of thyroid gland, with more secretion of thyroglobulin. Thyroglobulin, accumulates in the gland and causes enlargement of, the gland, resulting in non-toxic goiter., iii. High concentration of inorganic iodides, Iodides in high concentration decrease all phases of, thyroid activity, including the release of hormones. So,, , In advanced cases of hyperthyroidism, treatment by, using antithyroid substances is not possible. So, thyroid, gland of these patients must be removed. Surgical, removal of thyroid gland is called thyroidectomy. Before, surgery, the patient is prepared by reducing the basal, metabolic rate. It is done by injecting propylthiouracil, for several weeks, until basal metabolic rate reaches, almost the basal level. The high concentration of iodides, is administered for 2 weeks. It decreases the size of the, gland and blood supply to a very great extent. Because, of these precautions, the mortality after the operation, decreases very much., TREATMENT FOR HYPOTHYROIDISM, The only treatment for hypothyroidism is the administration of thyroid extract or ingestion of pure thyroxine in, the form of tablets, orally., , THYROID FUNCTION TESTS, Functional status of thyroid gland is assessed by the, following tests:, 1. Measurement of plasma level of T3 and T4: For, hyperthyroidism or hypothyroidism, the most, accurate diagnostic test is the direct measurement, of concentration of “free” thyroid hormones in the, plasma, i.e. T3 and T4., 2. Measurement of TRH and TSH: There is almost total, absence of these two hormones in hyperthyroidism., It is because of negative feedback mechanism, by, the increased level of thyroid hormones., 3. Measurement of basal metabolic rate: In hyperthyroidism, basal metabolic rate is increased, by about 30% to 60%. Basal metabolic rate is, decreased in hypothyroidism by 20% to 40%.
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Parathyroid Glands and, Physiology of Bone, , Chapter, , 68, , INTRODUCTION, PARATHORMONE, , , , , , , ACTIONS OF PARATHORMONE, ACTIONS ON BLOOD CALCIUM LEVEL, ACTIONS ON BLOOD PHOSPHATE LEVEL, MODE OF ACTION, REGULATION OF SECRETION, , APPLIED PHYSIOLOGY – DISORDERS OF PARATHYROID GLANDS, , , , , HYPOPARATHYROIDISM – HYPOCALCEMIA, HYPERPARATHYROIDISM – HYPERCALCEMIA, PARATHYROID FUNCTION TESTS, , CALCITONIN, , , , ACTIONS, REGULATION OF SECRETION, , CALCIUM METABOLISM, , , , , , , , , IMPORTANCE OF CALCIUM, NORMAL VALUE, TYPES OF CALCIUM, SOURCE OF CALCIUM, DAILY REQUIREMENTS, ABSORPTION AND EXCRETION, REGULATION OF BLOOD CALCIUM LEVEL, , PHOSPHATE METABOLISM, , , , , IMPORTANCE OF PHOSPHATE, NORMAL VALUE, REGULATION OF PHOSPHATE LEVEL, , PHYSIOLOGY OF BONE, , , , , , , , , , , , FUNCTIONS, CLASSIFICATION, PARTS, COMPOSITION, STRUCTURE, TYPES OF CELLS IN BONE, BONE GROWTH, BONE REMODELING, REPAIR OF BONE AFTER FRACTURE, APPLIED PHYSIOLOGY – DISEASES OF BONE
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400 Section 6 t Endocrinology, , INTRODUCTION, , Half-life and Plasma Level, , Human beings have four parathyroid glands, which are, situated on the posterior surface of upper and lower, poles of thyroid gland (Fig. 68.1). Parathyroid glands, are very small in size, measuring about 6 mm long, 3 mm, wide and 2 mm thick, with dark brown color., , Parathormone has a half-life of 10 minutes. Normal, plasma level of PTH is about 1.5 to 5.5 ng/dL., , Histology, Each parathyroid gland is made up of chief cells and, oxyphil cells. Chief cells secrete parathormone. Oxyphil, cells are the degenerated chief cells and their function is, known. However, these cells may secrete parathormone, during pathological condition called parathyroid adenoma., The number of oxyphil cells increases after puberty., , PARATHORMONE, Parathormone secreted by parathyroid gland is essential, for the maintenance of blood calcium level within a very, narrow critical level. Maintenance of blood calcium level, is necessary because calcium is an important inorganic, ion for many physiological functions (see below)., Source of Secretion, Parathormone (PTH) is secreted by the chief cells of the, parathyroid glands., Chemistry, Parathormone is protein in nature, having 84 amino, acids. Its molecular weight is 9,500., , Synthesis, Parathormone is synthesized from the precursor called, prepro-PTH containing 115 amino acids. First, the, prepro-PTH enters the endoplasmic reticulum of chief, cells of parathyroid glands. There it is converted into a, prohormone called pro-PTH, which contains 96 amino, acids. Pro-PTH enters the Golgi apparatus, where it is, converted into PTH., Metabolism, Sixty to seventy percent of PTH is degraded by Kupffer, cells of liver, by means of proteolysis. Degradation of, about 20% to 30% PTH occurs in kidneys and to a, lesser extent in other organs., ACTIONS OF PARATHORMONE, PTH plays an important role in maintaining blood calcium, level. It also controls blood phosphate level., ACTIONS OF PARATHORMONE, ON BLOOD CALCIUM LEVEL, Primary action of PTH is to maintain the blood calcium, level within the critical range of 9 to 11 mg/dL. The blood, calcium level has to be maintained critically because, it, is very important for many of the activities in the body., PTH maintains blood calcium level by acting on:, 1. Bones, 2. Kidney, 3. Gastrointestinal tract., 1. On Bone, Parathormone enhances the resorption of calcium, from the bones (osteoclastic activity) by acting on, osteoblasts and osteoclasts of the bone., Resorption of calcium from bones occurs in two, phases:, i. Rapid phase, ii. Slow phase., Rapid phase, , FIGURE 68.1: Parathyroid glands on the posterior, surface of thyroid gland, , Rapid phase occurs within minutes after the release of, PTH from parathyroid glands. Immediately after reaching, the bone, PTH gets attached with the receptors on the, cell membrane of osteoblasts and osteocytes. The, hormone-receptor complex increases the permeability of, membranes of these cells for calcium ions. It accelerates
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Chapter 68 t Parathyroid Glands and Physiology of Bone 401, the calcium pump mechanism, so that calcium ions, move out of these bone cells and enter the blood at a, faster rate., Slow phase, Slow phase of calcium resorption from bone is due to, the activation of osteoclasts by PTH. When osteoclasts, are activated, some substances such as proteolytic, enzymes, citric acid and lactic acid are released from, lysosomes of these cells. All these substances digest, or dissolve the organic matrix of the bone, releasing the, calcium ions. The calcium ions slowly enter the blood., PTH increases calcium resorption from bone by, stimulating the proliferation of osteoclasts also., 2. On Kidney, PTH increases the reabsorption of calcium from the, renal tubules along with magnesium ions and hydrogen, ions. It increases calcium reabsorption mainly from distal, convoluted tubule and proximal part of collecting duct., PTH also increases the formation of 1,25dihydroxycholecalciferol (activated form of vitamin D), from 25-hydroxycholecalciferol in kidneys (see below)., 3. On Gastrointestinal Tract, PTH increases the absorption of calcium ions from the, GI tract indirectly. It increases the formation of 1,25dihydroxycholecalciferol in the kidneys. This vitamin, in, turn increases the absorption of calcium from GI tract., Thus, the activated vitamin D is very essential for, the absorption of calcium from the GI tract. And PTH is, essential for the formation of activated vitamin D., , and is inhibited by 25-hydroxycholecalciferol itself by, feedback mechanism. This inhibition is essential for two, reasons:, i. Regulation of the amount of active vitamin D, ii. Storage of vitamin D for months together., If vitamin D3 is converted into 25-hydroxycholecalciferol, it remains in the body only for 2 to, 5 days. But vitamin D3 is stored in liver for several, months., Second step, 25-hydroxycholecalciferol is converted into 1,25dihydroxycholecalciferol (calcitriol) in kidney. It is the, active form of vitamin D3. This step needs the presence, of PTH., Role of Calcium Ion in Regulating, 1, 25-Dihydroxycholecalciferol, When blood calcium level increases, it inhibits the, formation, of, 1,25-dihydroxycholecalciferol., The, mechanism involved in the inhibition of the formation of, 1,25-dihydroxycholecalciferol is as follows:, i. Increase in calcium ion concentration directly, suppresses the conversion of 25-hydroxycholecalciferol into 1,25-dihydroxycholecalciferol., This effect is very mild, , Role of PTH in the activation of vitamin D, Vitamin D is very essential for calcium absorption, from the GI tract. But vitamin D itself is not an active, substance. Instead, vitamin D has to be converted into, 1, 25-dihydroxycholecalciferol in the liver and kidney in, the presence of PTH. The 1,25-dihydroxycholecalciferol, is the active product., Activation of vitamin D, There are various forms of vitamin D. But, the most, important one is vitamin D3. It is also known as cholecalciferol. Vitamin D3 is synthesized in the skin from, 7-dehydrocholesterol, by the action of ultraviolet rays from, the sunlight. It is also obtained from dietary sources., The activation of vitamin D3 occurs in two steps, (Fig. 68.2)., First step, Cholecalciferol (vitamin D3) is converted into 25hydroxycholecalciferol in the liver. This process is limited, , FIGURE 68.2: Schematic diagram showing, activation of vitamin D
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402 Section 6 t Endocrinology, ii. Increase in calcium ion concentration decreases, the PTH secretion, which in turn suppresses the, conversion of 25-hydroxycholecalciferol into, 1,25-dihydroxycholecalciferol., This regulates the calcium ion concentration of, plasma itself indirectly, i.e. when the PTH synthesis is, inhibited, the conversion of 25-hydroxycholecalciferol, into 1,25-hydroxycholecalciferol is also inhibited. Lack of, 1,25-dihydroxycholecalciferol, decreases the absorption, of calcium ions from the intestine, from the bones and, from the renal tubules as well. This makes the calcium, level in the plasma to fall back to normal., Actions of 1, 25-Dihydroxycholecalciferol, 1. It increases the absorption of calcium from the, intestine, by increasing the formation of calciumbinding proteins in the intestinal epithelial cells., These proteins act as carrier proteins for facilitated, diffusion, by which the calcium ions are transported., The proteins remain in the cells for several weeks, after 1,25-dihydroxycholecalciferol has been, removed from the body, thus causing a prolonged, effect on calcium absorption, 2. It increases the synthesis of calcium-induced, ATPase in the intestinal epithelium, 3. It increases the synthesis of alkaline phophatase in, the intestinal epithelium, 4. It increases the absorption of phosphate from, intestine along with calcium., ACTIONS OF PARATHORMONE, ON BLOOD PHOSPHATE LEVEL, PTH decreases blood level of phosphate by increasing, its urinary excretion. It also acts on bone and GI tract., , Sequence of events, i. PTH converts 25-hydroxycholecalciferol into, 1,25-dihydroxycholecalciferol (calcitriol: active, form of vitamin D3) in kidney, ii. Calcitriol increases the synthesis of calcium, induced ATPase in the intestinal epithelium, iii. ATPase increases the synthesis of alkaline, phophatase, iv. Alkaline phosphatase increases the absorption, of phosphate from intestine along with calcium., MODE OF ACTION OF PARATHORMONE, Parathormone Receptors, Parathormone receptors (PTH receptors) are of three, types, PTHR1, PTHR2 and PTHR3, which are G proteincoupled receptors. PTHR1 is physiologically more, important than the other two types. PTHR1 mediates, the actions of PTH and PTH-related protein (see below)., Role of PTHR2 and PTHR3 is not known clearly., On the target cells, PTH binds with PTHR1 which, is coupled to G protein and forms hormone-receptor, complex. Hormone-receptor complex causes formation, of cAMP, which acts as a second messenger for the, hormone., REGULATION OF, PARATHORMONE SECRETION, Blood level of calcium is the main factor regulating the, secretion of PTH. Blood phosphate level also regulates, PTH secretion., Blood Level of Calcium, , It is the effect of PTH by which phosphate is excreted, through urine. PTH increases phosphate excretion by, inhibiting reabsorption of phosphate from renal tubules., It acts mainly on proximal convoluted tubule., , Parathormone secretion is inversely proportional to, blood calcium level. Increase in blood calcium level, decreases PTH secretion., Conditions when PTH secretion decreases are:, 1. Excess quantities of calcium in the diet, 2. Increased vitamin D in the diet, 3. Increased resorption of calcium from the bones,, caused by some other factors such as bone, diseases., On the other hand, decrease in calcium ion, concentration of blood increases PTH secretion, as in, the case of rickets, pregnancy and in lactation., , 3. On Gastrointestinal Tract, , Blood Level of Phosphate, , Parathormone increases the absorption of phosphate, from GI tract through calcitriol., , PTH secretion is directly proportional to blood phosphate, level. Whenever the blood level of phosphate increases,, , 1. On Bone, Along with calcium resorption, PTH also increases, phosphate absorption from the bones., 2. On Kidney, Phosphaturic action
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Chapter 68 t Parathyroid Glands and Physiology of Bone 403, it combines with ionized calcium to form calcium, hydrogen phosphate. This decreases ionized calcium, level in blood which stimulates PTH secretion., , APPLIED PHYSIOLOGY – DISORDERS, OF PARATHYROID GLANDS, Disorders of parathyroid glands are of two types:, I. Hypoparathyroidism, II. Hyperparathyroidism., HYPOPARATHYROIDISM – HYPOCALCEMIA, Hyposecretion of PTH is called hypoparathyroidism., It leads to hypocalcemia (decrease in blood calcium, level)., Causes for Hypoparathyroidism, 1. Surgical, , removal, , of, , parathyroid, , glands, , (parathyroidectomy), , 2. Removal of parathyroid glands during surgical, removal of thyroid gland (thyroidectomy), 3. Autoimmune disease, 4. Deficiency of receptors for PTH in the target cells., In this, the PTH secretion is normal or increased, but the hormone cannot act on the target cells. This, condition is called pseudohypoparathyroidism., Hypocalcemia and Tetany, Hypoparathyroidism leads to hypocalcemia, by decreasing the resorption of calcium from bones. Hypocalcemia, causes neuromuscular hyperexcitability, resulting in, hypocalcemic tetany. Normally, tetany occurs when, plasma calcium level falls below 6 mg/dL from its normal, value of 9.4 mg/dL., Hypocalcemic Tetany, Tetany is an abnormal condition characterized by violent, and painful muscular spasm (spasm = involuntary, muscular contraction), particularly in feet and hand. It, is because of hyperexcitability of nerves and skeletal, muscles due to calcium deficiency., Signs and symptoms of hypocalcemic tetany:, 1. Hyper-reflexia and convulsions, Increase in neural excitability results in hyper-reflexia, (overactive reflex actions) and convulsive muscular, contractions., , FIGURE 68.3: Carpopedal spasm, , Attitude of hand in carpopedal spasm includes:, i. Flexion at wrist joint, ii. Flexion at metacarpophalangeal joints, iii. Extension at interphalangeal joints, iv. Adduction of thumb., 3. Laryngeal stridor, Stridor means noisy breathing. Laryngeal stridor means, a loud crowing sound during inspiration, which occurs, mainly due to laryngospasm (involuntary contraction, of laryngeal muscles). Laryngeal stridor is a common, dangerous feature of hypocalcemic tetany., , 4. Cardiovascular changes, i. Dilatation of the heart, ii. Prolonged duration of ST segment and QT, interval in ECG, iii. Arrhythmias (irregular heartbeat), iv. Hypotension, v. Heart failure., 5. Other features, i., ii., iii., iv., , Decreased permeability of the cell membrane, Dry skin with brittle nails, Hair loss, Grand mal, petit mal or other seizures (Chapter, 161), v. Signs of mental retardation in children or, dementia in adults (Chapter 162)., When the calcium level falls below 4 mg/dL, it, becomes fatal. During such severe hypocalcemic conditions, tetany occurs so quickly that a person develops, spasm of different groups of muscles in the body. Worst, affected are the laryngeal and bronchial muscles which, develop respiratory arrest, resulting in death., , 2. Carpopedal spasm, Carpopedal spasm is the spasm in hand and feet that, occurs in hypocalcemic tetany. During spasm, the hand, shows a peculiar attitude (Fig. 68.3)., , Latent Tetany, Latent tetany, also known as subclinical tetany is the, neuromuscular hyperexcitability due to hypocalcemia
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404 Section 6 t Endocrinology, that develops before the onset of tetany. It is, characterized by general weakness and cramps in feet, and hand. Hyperexcitability in these patients is detected, by some signs, which do not appear in normal persons., 1. Trousseau sign, Trousseau sign is the spasm of the hand that is, developed after 3 minutes of arresting the blood flow, to lower arm and hand. The blood flow to lower arm, and hand is arrested by inflating the blood pressure cuff, 20 mm Hg above the patient’s systolic pressure., 2. Chvostek sign, Chvostek sign is the twitch of the facial muscles, caused, by a gentle tap over the facial nerve in front of the ear. It, is due to the hyperirritability of facial nerve., 3. Erb sign, Hyperexcitability of the skeletal muscles even to a mild, electrical stimulus is called Erb sign. It is also called, Erb-Westphal sign., , HYPERPARATHYROIDISM – HYPERCALCEMIA, Hypersecretion of PTH is called hyperparathyroidism., It results in hypercalcemia. Hyperparathyroidism is of, three types:, 1. Primary hyperparathyroidism, Primary hyperparathyroidism is due to the development, of tumor in one or more parathyroid glands. Sometimes,, tumor may develop in all the four glands., 2. Secondary hyperparathyroidism, Secondary hyperparathyroidism is due to the physiological compensatory hypertrophy of parathyroid, glands, in response to hypocalcemia which occurs due, to other pathological conditions such as:, i. Chronic renal failure, ii. Vitamin D deficiency, iii. Rickets., 3. Tertiary hyperparathyroidism, Tertiary hyperparathyroidism is due to hyperplasia, (abnormal increase in the number of cells) of all, the parathyroid glands that develops due to chronic, secondary hyperparathyroidism., Hypercalcemia, Hypercalcemia is the increase in plasma calcium level., It occurs in hyperparathyroidism because of increased, resorption of calcium from bones., , Signs and symptoms of hypercalcemia, i. Depression of the nervous system, ii. Sluggishness of reflex activities, iii. Reduced ST segment and QT interval in ECG, iv. Lack of appetite, v. Constipation., Depressive effects of hypercalcemia are noticed, when the blood calcium level increases to 12 mg/dL., The condition becomes severe with 15 mg/dL and, it becomes lethal when blood calcium level reaches, 17 mg/dL., Other effects of hypercalcemia:, i. Development of bone diseases such as osteitis, fibrosa cystica, ii. Development of parathyroid poisoning. It is the, condition characterized by severe manifestations, that occur when blood calcium level rises, above 15 mg/dL. In hyperparathyroidism, the, concentration of both calcium and phosphate, increases leading to formation of calciumphosphate crystals. Concentration of phosphate, also increases because, kidney cannot excrete, the excess amount of phosphate resorbed from, the bone, iii. Deposition of calcium-phosphate crystals in renal, tubules, thyroid gland, alveoli of lungs, gastric, mucosa and in the wall of the arteries, resulting, in dysfunction of these organs. Renal stones are, formed when it is deposited in kidney., PARATHYROID FUNCTION TESTS, 1. Measurement of blood calcium level, 2. Chvostek sign and Trousseau sign for hypoparathyroidism., , CALCITONIN, Source of Secretion, Calcitonin is secreted by the parafollicular cells or, clear cells (C cells), situated amongst the follicles in, thyroid gland. In lower animals, the parafollicular cells, are derived from ultimobranchial glands, which develop, from fifth pharyngeal pouches. In human being, the, ultimobranchial glands and fifth pharyngeal pouches, are rudimentary and their cells are incorporated with, fourth pharyngeal pouches and distributed amongst the, follicles of thyroid gland., Recently, calcitonin is found in brain, prostate and, bronchial cells of lungs. However, the physiological role, of calcitonin from non-thyroid tissues is not known.
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Chapter 68 t Parathyroid Glands and Physiology of Bone 405, Chemistry and Synthesis, Calcitonin is a polypeptide chain with 32 amino acids. Its, molecular weight is about 3,400. It is synthesized from, procalcitonin., , cells. Gastrin also is known to stimulate the release of, calcitonin., , CALCIUM METABOLISM, , Plasma Level and Half-life, , IMPORTANCE OF CALCIUM, , Plasma level of calcitonin is 1 to 2 ng/dL. It has a halflife of 5 to 10 minutes., , Calcium is very essential for many activities in the body, such as:, 1. Bone and teeth formation, 2. Neuronal activity, 3. Skeletal muscle activity, 4. Cardiac activity, 5. Smooth muscle activity, 6. Secretory activity of the glands, 7. Cell division and growth, 8. Coagulation of blood., , Metabolism, Calcitonin is degraded and excreted by liver and kidney., ACTIONS OF CALCITONIN, 1. On Blood Calcium Level, Calcitonin plays an important role in controlling the blood, calcium level. It decreases the blood calcium level and, thereby counteracts parathormone., Calcitonin reduces the blood calcium level by acting, on bones, kidneys and intestine., i. On bones, Calcitonin stimulates osteoblastic activity and facilitates, the deposition of calcium on bones. At the same time,, it suppresses the activity of osteoclasts and inhibits the, resorption of calcium from bones. It inhibits even the, development of new osteoclasts in bones., ii. On kidney, Calcitonin increases excretion of calcium through urine,, by inhibiting the reabsorption from the renal tubules., iii. On intestine, Calcitonin prevents the absorption of calcium from, intestine into the blood., 2. On Blood Phosphate Level, With respect to calcium, calcitonin is an antagonist to, PTH. But it has similar actions of PTH, with respect to, phosphate. It decreases the blood level of phosphate by, acting on bones and kidneys., i. On bones, Calcitonin inhibits the resorption of phosphate from bone, and stimulates the deposition of phosphate on bones., ii. On kidney, Calcitonin increases the excretion of phosphate through, urine, by inhibiting the reabsorption from renal tubules., REGULATION OF CALCITONIN SECRETION, High calcium content in plasma stimulates the calcitonin, secretion through a calcium receptor in parafollicular, , NORMAL VALUE, In a normal young healthy adult, there is about 1,100, g of calcium in the body. It forms about 1.5% of total, body weight. 99% of calcium is present in the bones, and teeth and the rest is present in the plasma. Normal, blood calcium level ranges between 9 and 11 mg/dL., TYPES OF CALCIUM, Calcium in Plasma, Calcium is present in three forms in plasma:, i. Ionized or diffusible calcium: Found freely in, plasma and forms about 50% of plasma calcium., It is essential for vital functions such as neuronal, activity, muscle contraction, cardiac activity,, secretions in the glands, blood coagulation, etc., ii. Non-ionized or non-diffusible calcium: Present, in non-ionic form such as calcium bicarbonate., It is about 8% to 10% of plasma calcium, iii. Calcium bound to albumin: Forms about 40% to, 42% of plasma calcium., Calcium in Bones, Calcium is constantly removed from bone and deposited, in bone. Bone calcium is present in two forms:, i. Rapidly exchangeable calcium or exchangeable, calcium: Available in small quantity in bone and, helps to maintain the plasma calcium level, ii. Slowly exchangeable calcium or stable calcium:, Available in large quantity in bones and helps in, bone remodeling., Process of calcium metabolism is explained, schematically in Fig. 68.4.
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406 Section 6 t Endocrinology, , FIGURE 68.4: Schematic diagram showing calcium metabolism. Values belong to adults, , SOURCE OF CALCIUM, , ABSORPTION AND EXCRETION, OF CALCIUM, , 1. Dietary Source, Calcium is available in several foodstuffs. Percentage of, calcium in different food substance is:, Whole milk, = 10%, Low fat milk, = 18%, Cheese, = 27%, Other dairy products, = 17%, Vegetables, = 7%, Other substances such as, meat, egg, grains, sugar,, coffee, tea, chocolate, etc. = 21%, 2. From Bones, Besides dietary calcium, blood also gets calcium from, bone by resorption., DAILY REQUIREMENTS OF CALCIUM, 1 to 3 years, 4 to 8 years, 9 to 18 years, 19 to 50 years, 51 years and above, Pregnant ladies and, lactating mothers, , = 500 mg, = 800 mg, = 1,300 mg, = 1,000 mg, = 1,200 mg, = 1,300 mg, , Calcium taken through dietary sources is absorbed from, GI tract into blood and distributed to various parts of the, body. Depending upon the blood level, the calcium is, either deposited in the bone or removed from the bone, (resorption). Calcium is excreted from the body through, urine and feces., Absorption from Gastrointestinal Tract, Calcium is absorbed from duodenum by carriermediated active transport and from the rest of the small, intestine, by facilitated diffusion. Vitamin D is essential, for the absorption of calcium from GI tract., Excretion, While passing through the kidney, large quantity of, calcium is filtered in the glomerulus. From the filtrate,, 98% to 99% of calcium is reabsorbed from renal tubules, into the blood. Only a small quantity is excreted through, urine., Most of the filtered calcium is reabsorbed in the distal, convoluted tubules and proximal part of collecting duct., In distal convoluted tubule, parathormone increases the, reabsorption. In collecting duct, vitamin D increases the, reabsorption and calcitonin decreases reabsorption.
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Chapter 68 t Parathyroid Glands and Physiology of Bone 407, , FIGURE 68.5: Schematic diagram showing regulation of blood calcium level, , About 1,000 mg of calcium is excreted daily. Out, of this, 900 mg is excreted through feces and 100 mg, through urine., , reduces the blood calcium level mainly by decreasing, bone resorption (see above for details)., Effects of Other Hormones, , REGULATION OF BLOOD CALCIUM LEVEL, Blood calcium level is regulated mainly by three, hormones (Figs 68.5 and 68.6):, 1. Parathormone, 2. 1,25-dihydroxycholecalciferol (calcitriol), 3. Calcitonin., , In addition to the above mentioned three hormones,, growth hormone and glucocorticoids also influence the, calcium level., , 1. Parathormone, Parathormone is a protein hormone secreted by, parathyroid gland and its main function is to increase, the blood calcium level by mobilizing calcium from bone, (resorption) (See above for details)., 2. 1,25-dihydroxycholecalciferol – Calcitriol, Calcitriol is a steroid hormone synthesized in kidney., It is the activated form of vitamin D. Its main action is, to increase the blood calcium level by increasing the, calcium absorption from the small intestine (see above, for details)., 3. Calcitonin, Calcitonin secreted by parafollicular cells of thyroid, gland. Thyroid gland is a calcium-lowering hormone. It, , FIGURE 68.6: Effect of hormones on blood calcium level
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408 Section 6 t Endocrinology, 1. Growth hormone, , 1. Parathormone, , Growth hormone increases the blood calcium level by, increasing the intestinal calcium absorption. It is also, suggested that it increases the urinary excretion of, calcium. However, this action is only transient., , Parathormone stimulates resorption of phosphate from, bone and increases its urinary excretion. It also increases, the absorption of phosphate from gastrointestinal tract, through calcitriol. The overall action of parathormone, decreases the plasma level of phosphate., , 2. Glucocorticoids, Glucocorticoids (cortisol) decrease blood calcium by, inhibiting intestinal absorption and increasing the renal, excretion of calcium., , PHOSPHATE METABOLISM, , 2. Calcitonin, Calcitonin also decreases the plasma level of phosphate, by inhibiting bone resorption and stimulating the urinary, excretion., , Phosphorus (P) is an essential mineral that is required, , 3. 1,25-Dihydroxycholecalciferol – Calcitriol, , by every cell in the body for normal function. Phosphorus, is present in many food substances, such as peas,, dried beans, nuts, milk, cheese and butter. Inorganic, phosphorus (Pi) is in the form of the phosphate (PO4)., The majority of the phosphorus in the body is found as, phosphate. Phosphorus is also the body’s source of, phosphate. In body, phosphate is the most abundant, intracellular anion., , Calcitriol hormone increases absorption of phosphate, from small intestine (Fig. 68.7)., Effects of Other Hormones, In addition to the above mentioned three hormones,, growth hormone and glucocorticoids also influence the, phosphate level., 1. Growth hormone, , IMPORTANCE OF PHOSPHATE, 1. Phosphate is an important component of many, organic substances such as, ATP, DNA, RNA and, many intermediates of metabolic pathways, 2. Along with calcium, it forms an important constituent, of bone and teeth, 3. It forms a buffer in the maintenance of acid-base, balance., , Growth hormone increases the blood phosphate level, by increasing the intestinal phosphate absorption., 2. Glucocorticoids, Glucocorticoids (cortisol) decreases blood phosphate, by inhibiting intestinal absorption and increasing the, renal excretion of phosphate., , NORMAL VALUE, Total amount of phosphate in the body is 500 to 800 g., Though it is present in every cell of the body, 85% to, 90% of body’s phosphate is found in the bones and, teeth. Normal plasma level of phosphate is 4 mg/dL., REGULATION OF PHOSPHATE LEVEL, Phosphorus is taken through dietary sources. It is, absorbed from GI tract into blood. It is also resorbed, from bone. From blood it is distributed to various parts, of the body. While passing through the kidney, large, quantity of phosphate is excreted through urine., Blood phosphate level is regulated mainly by three, hormones:, 1. Parathormone, 2. Calcitonin, 3. 1,25-dihydroxycholecalciferol (calcitriol)., , FIGURE 68.7: Effect of hormones on blood phosphate level
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Chapter 68 t Parathyroid Glands and Physiology of Bone 409, , PHYSIOLOGY OF BONE, Bone or osseous tissue is a specialized rigid connective, tissue that forms the skeleton. It consists of special, type of cells and tough intercellular matrix of ground, substance. The matrix is formed by organic substances, like collagen and it is strengthened by the deposition, of mineral salts like calcium phosphate and calcium, carbonate. Throughout the life, bone is renewed by the, process of bone formation and bone resorption., FUNCTIONS OF BONE, 1. Protective function: Protects soft tissues and vital, organs of the body, 2. Mechanical function: Supports the body and, brings out various movements of the body by their, attachment to the muscles and tendons, 3. Metabolic function: Plays an important role in the, metabolism homeostasis of calcium and phosphate, in the body., 4. Hemopoietic function: Red bone marrow in the, bones is the site of production of blood cells., FIGURE 68.8: Parts of long bone, , CLASSIFICATION OF BONE, Depending upon the size and shape, the bones are, classified into five types:, 1. Long bones: Bones of the limbs, 2. Short bones: Bones in the wrist and ankle, 3. Flat bones: Skull bones, mandible, scapula, etc., 4. Irregular bones: Vertebra, 5. Sesamoid bones: Patella., PARTS OF BONE, Long bones are formed by a cylindrical tube of bone, tissue, which has three portions:, 1. Diaphysis: Midportion or midshaft, 2. Epiphysis: Wider extremity or the head on either, end, 3. Metaphysis: Portion between the diaphysis and the, epiphysis (Fig. 68.8)., In growing age, a layer of cartilage called epiphyseal, cartilage or epiphyseal plate or growth plate is present, in between epiphysis and metaphysis. Epiphyseal plate, is responsible for the longitudinal growth of the bones., COMPOSITION OF BONE, Bone consists of the tough organic matrix to which the, bone salts are deposited., , Matrix, Bone matrix is composed of protein fibers called, collagen fibers, which are embedded in the gelatinous, ground substance. These collagen fibers form about, 90% of the bone. The ground substance is formed by, ECF and proteoglycans. Proteoglycans are chondroitin, sulfate and hyaluronic acid, which are concerned with, the regulation and deposition of bone salts., Bone Salts, The crystalline salts present in bones are called, hydroxyapatites, which contain calcium and phosphate., Apart from these substances, some other salts like, sodium, potassium, magnesium and carbonate are also, present in the bone. The salts of the bone strengthen, the bone matrix., STRUCTURE OF BONE, Bone is covered by an outer white fibrous connective, layer called periosteum and an inner dense fibrous, membrane called endosteum. The tendons from, the muscles are attached to periosteum. The heads, (epiphysis) of bone are covered by a hyaline cartilage., It forms the synovial joint with adjoining bones.
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410 Section 6 t Endocrinology, Bones have two layers of structures:, 1. Outer compact bone, 2. Inner spongy bone., In most of the bones, both compact and spongy, forms are present. However, the thickness of each type, varies in different regions. The epiphysis contains large, amount of spongy bone and outer thin compact bone. In, diaphysis, the amount of compact bone is more and the, spongy bone is very thin., Compact Bone, Compact or cortical bone is the hard and dense material, forming about 80% of bone in the body. Its main, functions are mechanical function and the protection of, bone marrow., Compact bone consists of minute cylindrical, structures called osteones or Haversian systems (Fig., 68.9), which are formed by concentric layers of collagen., Collagen lamellae are called Haversian lamellae. In the, center of each osteon, there is a canal called Haversian, canal that contains the blood vessels, lymph vessels, and nerve fibers. The Haversian systems communicate, with each other by transverse canals called Volkmann, canal., , Within the Haversian systems, there are small, cavities called lacunae, inside which the osteocytes, are trapped. Osteocytes send long processes called, canaliculi. The canaliculi from neighboring osteocytes, unite to form tight junctions., Marrow cavity, Compact bone has a large narrow cavity called marrow, cavity or medullary cavity, which contains yellow bone, marrow., Spongy Bone, Spongy or trabecular or cancellous bone forms 20%, of bone in the body and it contains red bone marrow., It is made of bone spicules, which are separated by, spaces., TYPES OF CELLS IN BONE, Bone has three major types of cells:, 1. Osteoblasts, 2. Osteocytes, 3. Osteoclasts., , FIGURE 68.9: Structure of compact bone, , epiphyseal plate. The osteoblasts arise from the giant, multinucleated primitive cells called the osteoprogenitor, cells. Differentiation of osteoprogenitor cells into, osteoblasts (Table 68.1) is accelerated by some, hormones and some bone proteins called skeletal, growth factors. These growth factors stimulate the, growth of osteoblasts also., Functions of osteoblasts, i. Role in the formation of bone matrix, Osteoblasts are responsible for the synthesis of bone, matrix by secreting type I collagen and a protein called, matrix gla protein (MGP) or osteocalcin. Other proteins, involved in the matrix synthesis are also produced by, the osteoblasts. Such proteins are transforming growth, factor (TGF), insulin-like growth factor (IGF), fibroblast, growth factor (FGF) and platelet-derived growth factor, (PDGF)., ii. Role in calcification, Osteoblasts are rich in enzyme alkaline phosphatase,, which is necessary for deposition of calcium in the bone, matrix (calcification)., , 1. Osteoblasts, , iii. Synthesis of proteins, , Osteoblasts are the bone cells concerned with bone, formation (osteoblastic activity). These cells are situated, in the outer surface of bone, the marrow cavity and, , Osteoblasts synthesize the proteins called matrix gla, protein and osteopontin, which are involved in the, calcification.
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Chapter 68 t Parathyroid Glands and Physiology of Bone 411, Fate of osteoblasts, After taking part in bone formation, the osteoblasts, differentiate into osteocytes, which are trapped inside, the lacunae of calcified bone., 2. Osteocytes, Osteocytes are the bone cells concerned with, maintenance of bone. Osteocytes are small flattened and, rounded cells, embedded in the bone lacunae. These, cells are the major cells in developed bone and are, derived from the matured osteoblasts. The cytoplasmic, processes from osteocytes run into canaliculi and, ramify throughout the bone matrix. The processes from, neighboring osteocytes have contact with each other, forming tight junctions., Functions of osteocytes, i. Help to maintain the bone as living tissue, because of their metabolic activity, ii. Maintain the exchange of calcium between the, bone and ECF., 3. Osteoclasts, Osteoclasts are the bone cells that are concerned with, bone resorption (osteoclastic activity). Osteoclasts are, the giant phagocytic multinucleated cells found in the, lacunae of bone matrix. These bone cells are derived, from hemopoietic stem cells via monocytes colony, forming units-M (CFU-M)., Functions of osteoclasts, i. Responsible for bone resorption during bone, remodeling, ii. Synthesis and release of lysosomal enzymes, necessary for bone resorption into the bone, resorbing compartment., BONE GROWTH, Embryo has a cartilaginous skeleton. The cartilage is, composed of large amount of solid but flexible matrix., The matrix is derived from a protein called chondrin,, that is secreted by the cartilage cells or chondriocytes., Some of the cartilage is converted into bones., Ossification and Calcification, Ossification is the conversion of cartilage into bone. At, the time of birth, the skeleton consists of 50% cartilage, and 50% bone. At the age of 2 years and thereafter, the, skeleton consists 35% cartilage and 65% bone., Ossification is carried out by the osteoblasts, which, enter the cartilage and lay down the matrix around, , them. Osteoblasts synthesize collagen fibers, which, produce the matrix called osteoid. Then, calcium is, deposited on the matrix. The deposition of calcium is, called calcification., Growth in Length, During growth, the epiphysis at the end of each long bone, is separated from diaphysis by a plate of proliferative, cartilage termed as epiphyseal plate., Increase in the length of the bone occurs due to, the formation of new bone from epiphyseal plate. The, thickness of the epiphyseal plate reduces as the length, of bone increases. Increase in length of the bone occurs, as long as the epiphyseal plates remain separated from, diaphysis (shaft). The growth of the bone stops when, the epiphysis fuses with the shaft. The process by which, epiphysis fuses with shaft is called the epiphyseal fusion, or closure. It occurs usually at the time of puberty. Width, of the bone increases due to increase in thickness of, periosteum or the outer layers of compact bone., BONE REMODELING, Bone remodeling is a dynamic lifelong process in, which old bone is resorbed and new bone is formed., Usually, it takes place in groups of bone cells called the, basic multicellular units (BMU). The entire process of, remodeling extends for about 100 days in compact bone, and about 200 days in spongy bone., Processes of bone remodeling, 1. Bone resorption: Destruction of bone matrix and, removal of calcium (osteoclastic activity)., 2. Bone formation: Development and mineralization of, new matrix (osteoblastic activity)., Bone Resorption – Osteoclastic Activity, Osteoclastic activity is the process that involves, destruction of bone matrix, followed by removal of, calcium. Osteoclasts are responsible for bone resorption, by their osteoclastic activity., Part of the bone to be resorbed is known as bone, resorbing compartment. The osteoclast present in, this compartment attaches itself to the periosteal or, endosteal surface of bone through villi-like membranous, extensions. This process is mediated by the surface, receptors called integrins. At the point of attachment, a, ruffled border is formed by folding of the cell membrane., Resorption of that particular compartment occurs, by some substances released from membranous extensions of osteoclasts such as:, 1. Collagenase, 2. Phosphatase
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412 Section 6 t Endocrinology, 3. Lysosomal enzymes, 4. Acids like citric acid and lactic acid., Sequence of events during bone resorption, 1. Citric acid and lactic acid cause acidification of the, area and decrease pH to 4, 2. Lysosomal enzymes are activated at this pH, 3. Activated enzymes digest or dissolve the collagen, 4. Enzymes also dissolve the hydroxyapatite and form, solution of bone salts, 5. All the dissolved materials are now released into, ECF, 6. Some elements enter the blood, 7. Remaining elements are cleaned up by the, macrophages, 8. A shallow cavity is formed in the bone resorbing, compartment., Bone Formation – Osteoblastic Activity, Osteoblastic activity is the process which involves the, synthesis of collagen and formation of bone matrix that, is mineralized. Osteoblasts are concerned with bone, formation. Osteoblasts synthesize and release collagen, into the shallow cavity formed after resorption in the bone, resorbing compartment. The collagen fibers arrange, themselves in regular units and form the organic matrix, called osteoid., Mineralization, Mineralization is the process by which the minerals are, deposited on bone matrix. Mineralization starts about 10, to 12 days after the formation of osteoid. First, a large, quantity of calcium phosphate is deposited. Afterwards,, the hydroxide and bicarbonate ions are gradually added, causing the formation of hydroxyapatite crystals., The process of mineralization is accelerated by the, enzyme alkaline phosphatase, secreted by osteoblast., The process also requires the availability of adequate, amount of calcium and phosphate in the ECF., The completely mineralized bone surrounds the, osteoblast. Now, the synthetic activity of osteoblast is, reduced slowly and the cell is converted into osteocytes., Later, the bone is arranged in concentric lamellae on the, inner surface of the cavity. At the end of the formation, of new bone, the cavity is reduced to form Haversian, canal., Significance of Bone Remodeling, In children, 1. Thickness of bone increases, 2. Bone obtains strength in proportion to the growth, , 3. Shape of the bone is realtered in relation to growth, of the body., In adults, 1. Toughness of bone is maintained, 2. Mechanical integrity of skeleton, throughout life, 3. Blood calcium level is maintained., , is, , ensured, , Regulation of Bone Remodeling, Bone remodeling occurs continuously throughout the, life. So a balance is maintained always between the, bone resorption and bone formation., However, in persons like athletes, soldiers and, others, in whom the bone stress is more, the bone, becomes heavy and strong. It is because of the, stimulation of osteoblastic activity and mineralization of, bone by repeated physical stress., Apart from the physical stress, a variety of hormonal, substances and growth factors are involved in regulation, of bone resorption and bone formation (Table 68.1)., REPAIR OF BONE AFTER FRACTURE, The process of healing after bone fracture involves, joining of broken ends by the deposition of new bone., Stages of Bone Repair after Fracture, 1. Formation of hematoma between the broken ends, of bone and surrounding soft tissues. Hematoma, means swelling or mass of blood clot confined to a, tissue or space due to rupture of blood vessel, 2. Development of acute inflammation, 3. Phagocytosis of hematoma, debris and fragments, of bone by macrophages, 4. Formation of granular tissue and development of, new blood vessels, 5. Development of new osteoblasts and formation of, new bone called callus, 6. Spreading of new bone to fill the gap between the, broken ends of bones, 7. Reshaping of new bone by osteoclasts, which, remove excess callus and formation of canal in the, new bone., APPLIED PHYSIOLOGY –, DISEASES OF BONE, 1. Osteoporosis, Osteoporosis is the bone disease characterized by the, loss of bone matrix and minerals. Osteoporosis means, ‘porous bones’.
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Chapter 68 t Parathyroid Glands and Physiology of Bone 413, TABLE 68.1: Factors regulating bone remodeling, Event, , Stimulating factors, , Inhibiting Factors, , Bone formation, , 1. Growth hormone, 2. Calcitonin, 3. Insulin, 4. Testosterone, 5. Estrogen, 6. Insulin-like growth factor, 7. Transforming growth factor-β, 8. Skeletal growth factor, 9. Bone-derived growth factor, 10. Platelet-derived growth factor, , Cortisol, , Mineralization, , 1. Calcitonin, 2. Insulin, 3. Vitamin D, , Cortisol, , Bone resorption, , 1. Parathormone, 2. Thyroxine, 3. Cortisol, 4. Prostaglandins, 5. Interleukin-1, 6. Estrogen, 7. Calcitonin, , Testosterone, , Causes of osteoporosis, Osteoporosis occurs due to excessive bone resorption, and decreased bone formation. Osteoporosis is common, in women after 60 years. The various risk factors are, given in Box 68.1., Manifestations of osteoporosis, Loss of bone matrix and minerals leads to loss of bone, strength, associated with architectural deterioration of, bone tissue. Ultimately, the bones become fragile with, high risk of fracture. Commonly affected bones are, vertebrae and hip., 2. Rickets, Rickets is the bone disease in children, characterized by, inadequate mineralization of bone matrix. It occurs due, to vitamin D deficiency. Vitamin D deficiency develops, due to insufficiency in diet or due to inadequate exposure, to sunlight., BOX 68.1: Risk factors for osteoporosis, 1. Sedentary life, 2. Genetic factor, 3. Early menopause or ovariectomy, 4. Excessive smoking, 5. Excessive alcohol or caffeine intake, 6. Prolonged high intake of protein, 7. Prolonged medication with drugs like corticosteroids and, cyclosporin, 8. Endocrine disorders like hypothyroidism, Cushing, syndrome, acromegaly and hypogonadism., , Deficiency of vitamin D affects the reabsorption of, calcium and phosphorus from renal tubules, resulting in, calcium deficiency. It causes inadequate mineralization, of epiphyseal growth plate in growing bones. This defect, produces various manifestations., Causes of rickets, Causes of rickets are given in Table 68.2., Features of rickets, i. Collapse of chest wall: Due to the flattening of, sides of thorax with prominent sternum. This, deformity of the chest with projecting sternum is, called pigeon chest or chicken chest or pectus, carinatum., , ii. Rachitic rosary: A visible swelling where the, ribs join their cartilages. It is because of the, development of nodules at sternal end of ribs,, which forms the rachitic rosary, iii. Kyphosis: Extreme forward curvature of the, upper back bone (thoracic spine) with convexity, backward (forward bending). Severe kyphosis, TABLE 68.2: Common causes of rickets, and osteomalacia, Deficiency of, vitamin D, , Low dietary intake, Inadequate synthesis in skin, Reduced absorption from intestine, , Renal diseases, , Chronic renal failure, Dialysis-induced bone disease, Renal tubular acidosis.
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414 Section 6 t Endocrinology, causes formation of a hump (protuberance), which is called humpback, hunchback or Pott, curvature, , iv. Lordosis: Extreme forward curvature of back, bone in lumbar region: also called hollow back, or saddle back, v. Scoliosis: Lateral curvature of spine, vi. Harrison sulcus: A groove in rib cage due to, pulling of diaphragm inwards, vii. Bowing of hands and legs, viii. Enlargement of liver and spleen, ix. Tetany: In advanced stages, the patient may, die because of tetany, involving the respiratory, muscles., , 3. Osteomalacia, Rickets in adults is called osteomalacia or adult rickets., Causes of osteomalacia, Osteomalacia occurs because of deficiency of vitamin, D. It also occurs due to prolonged damage of kidney, (renal rickets)., Features of osteomalacia, i. Vague pain, ii. Tenderness in bones and muscles, iii. Myopathy leading to waddling gait (gait means, the manner of walking). In waddling gait, the feet, are wide apart and walk resembles that of a duck, iv. Occasional hypoglycemic tetany.
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Endocrine Functions, of Pancreas, , , , , , , , , Chapter, , 69, , ISLETS OF LANGERHANS, INSULIN, GLUCAGON, SOMATOSTATIN, PANCREATIC POLYPEPTIDE, REGULATION OF BLOOD GLUCOSE LEVEL, APPLIED PHYSIOLOGY, , ISLETS OF LANGERHANS, , SYNTHESIS, , Endocrine function of pancreas is performed by the, islets of Langerhans. Human pancreas contains about, 1 to 2 million islets., Islets of Langerhans consist of four types of cells:, 1. A cells or α-cells, which secrete glucagon, 2. B cells or β-cells, which secrete insulin, 3. D cells or δ-cells, which secrete somatostatin, 4. F cells or PP cells, which secrete pancreatic, polypeptide., , Synthesis of insulin occurs in the rough endoplasmic, reticulum of β-cells in islets of Langerhans. It is synthesized as preproinsulin, that gives rise to proinsulin., Proinsulin is converted into insulin and C peptide through, a series of peptic cleavages. C peptide is a connecting, peptide that connects α and β chains. At the time of, secretion, C peptide is detached., Preproinsulin → Proinsulin, Peptic cleavage ↓, Insulin, , INSULIN, SOURCE OF SECRETION, Insulin is secreted by B cells or the β-cells in the islets of, Langerhans of pancreas., , METABOLISM, Binding of insulin to insulin receptor is essential for its, removal from circulation and degradation. Insulin is, degraded in liver and kidney by a cellular enzyme called, insulin protease or insulin-degrading enzyme., , CHEMISTRY AND HALF-LIFE, Insulin is a polypeptide with 51 amino acids and a, molecular weight of 5,808. It has two amino acid chains, called α and β chains, which are linked by disulfide, bridges. The α-chain of insulin contains 21 amino acids, and β-chain contains 30 amino acids. The biological, half-life of insulin is 5 minutes., , ACTIONS OF INSULIN, Insulin is the important hormone that is concerned with, the regulation of carbohydrate metabolism and blood, glucose level. It is also concerned with the metabolism, of proteins and fats., 1. On Carbohydrate Metabolism, , PLASMA LEVEL, Basal level of insulin in plasma is 10 µU/mL., , Insulin is the only antidiabetic hormone secreted in, the body, i.e. it is the only hormone in the body that
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416 Section 6 t Endocrinology, reduces blood glucose level. Insulin reduces the blood, glucose level by its following actions on carbohydrate, metabolism:, i. Increases transport and uptake of glucose by the cells, Insulin facilitates the transport of glucose from blood, into the cells by increasing the permeability of cell membrane to glucose. Insulin stimulates the rapid uptake of, glucose by all the tissues, particularly liver, muscle and, adipose tissues. But, it is not required for glucose uptake, in some tissues such as brain (except hypothalamus),, renal tubules, mucous membrane of intestine and, RBCs. Insulin also increases the number of glucose, transporters, especially GLUT 4 in the cell membrane., Glucose transporters: Usually, glucose is transported into, the cells by sodium-glucose symport pump. In addition, to symport pump, most of the cells have another type of, transport proteins called glucose transporters (GLUT)., So far, seven types of GLUT are identified (GLUT 1–7)., Among these, GLUT4 is insulin sensitive and it is located, in cytoplasmic vesicles. It is present in large numbers in, muscle fibers and adipose cells., When insulin-receptor complex is formed in the, membrane of such cells, the vesicles containing GLUT4, are attracted towards the membrane and GLUT4, is released into the membrane. Now, GLUT4 starts, transporting the glucose molecules from extracellular, fluid (ECF) into the cell. The advantage of GLUT4 is that, it transports glucose at a faster rate., ii. Promotes peripheral utilization of glucose, Insulin promotes the peripheral utilization of glucose., In presence of insulin, glucose which enters the cell is, oxidized immediately. The rate of utilization depends, upon the intake of glucose., iii. Promotes storage of glucose – glycogenesis, Insulin promotes the rapid conversion of glucose into, glycogen (glycogenesis), which is stored in the muscle, and liver. Thus, glucose is stored in these two organs, in the form of glycogen. Insulin activates the enzymes, which are necessary for glycogenesis. In liver, when, glycogen content increases beyond its storing capacity,, insulin causes conversion of glucose into fatty acids., iv. Inhibits glycogenolysis, Insulin prevents glycogenolysis, i.e. the breakdown of, glycogen into glucose in muscle and liver., v. Inhibits gluconeogenesis, Insulin prevents gluconeogenesis, i.e. the formation of, glucose from proteins by inhibiting the release of amino, acids from muscle and by inhibiting the activities of, enzymes involved in gluconeogenesis., , Thus, insulin decreases the blood glucose level by:, i. Facilitating transport and uptake of glucose by, the cells, ii. Increasing the peripheral utilization of glucose, iii. Increasing the storage of glucose by converting, it into glycogen in liver and muscle, iv. Inhibiting glycogenolysis, v. Inhibiting gluconeogenesis., 2. On Protein Metabolism, Insulin facilitates the synthesis and storage of proteins, and inhibits the cellular utilization of proteins by the, following actions:, i. Facilitating the transport of amino acids into the, cell from blood, by increasing the permeability of, cell membrane for amino acids, ii. Accelerating protein synthesis by influencing, the transcription of DNA and by increasing the, translation of mRNA, iii. Preventing protein catabolism by decreasing, the activity of cellular enzymes which act on, proteins, iv. Preventing conversion of proteins into glucose., Thus, insulin is responsible for the conservation, and storage of proteins in the body., 3. On Fat Metabolism, Insulin stimulates the synthesis of fat. It also increases, the storage of fat in the adipose tissue., Actions of insulin on fat metabolism are:, i. Synthesis of fatty acids and triglycerides, Insulin promotes the transport of excess glucose into, cells, particularly the liver cells. This glucose is utilized, for the synthesis of fatty acids and triglycerides. Insulin, promotes the synthesis of lipids by activating the, enzymes which convert:, a. Glucose into fatty acids, b. Fatty acids into triglycerides., ii. Transport of fatty acids into adipose tissue, Insulin facilitates the transport of fatty acids into the, adipose tissue., iii. Storage of fat, Insulin promotes the storage of fat in adipose tissue by, inhibiting the enzymes which degrade the triglycerides., 4. On Growth, Along with growth hormone, insulin promotes growth of, body by its anabolic action on proteins. It enhances the
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Chapter 69 t Endocrine Functions of Pancreas 417, transport of amino acids into the cell and synthesis of, proteins in the cells. It also has the protein-sparing effect,, i.e. it causes conservation of proteins by increasing the, glucose utilization by the tissues., Houssay Animal, The importance of insulin and growth hormone in the, growth of the body is demonstrated by Houssay animal., Houssay animal is one in which both anterior pituitary, and pancreas are removed. Administration of either, insulin or growth hormone alone does not induce growth, in this animal. However, the administration of both, the hormones stimulates the growth. This proves the, synergistic actions of these two hormones on growth., MODE OF ACTION OF INSULIN, On the target cells, insulin binds with the receptor protein, and forms the insulin-receptor complex. This complex, executes the action by activating the intracellular, enzyme system., Insulin Receptor, Insulin receptor is a glycoprotein with a molecular weight, of 340,000. It is present in almost all the cells of the, body., Subunits of insulin receptor, Insulin receptor is a tetramer, formed by four glycoprotein, subunits (two α-subunits and two β-subunits). The, α-subunits protrude out of the cell and the β-subunits, protrude inside the cell (Fig. 69.1). The α and β subunits, are linked to each other by disulfide bonds. Intracellular, surfaces of α-subunits have the enzyme activity –, protein kinase (tyrosine kinase) activity., When insulin binds with α-subunits of the receptor, protein, the tyrosine kinase at the β-subunit (that, protrudes into the cell) is activated by means of, autophosphorylation., Activated tyrosine kinase acts on many intracellular, enzymes by phosphorylating or dephosphorylating them, so that some of the enzymes are activated while others, are inactivated., Thus, insulin action is exerted on the target cells by, the activation of some intracellular enzymes and by the, inactivation of other enzymes., REGULATION OF INSULIN SECRETION, Insulin secretion is mainly regulated by blood glucose, level., , FIGURE 69.1: Diagram showing the structure of, insulin receptor. S–S = Disulfide bond., , In addition, other factors like amino acids, lipid, derivatives, gastrointestinal and endocrine hormones, and autonomic nerve fibers also stimulate insulin, secretion., 1. Role of Blood Glucose Level, When blood glucose level is normal (80 to 100 mg/dL),, the rate of insulin secretion is low (up to 10 µU/minute)., When blood glucose level increases between 100 and, 120 mg/dL, the rate of insulin secretion rises rapidly to, 100 µU/minute. When blood glucose level rises above, 200 mg/dL, the rate of insulin secretion also rises very, rapidly up to 400 µU/minute., Biphasic effect of glucose, Action of blood glucose on insulin secretion is biphasic., i. Initially, when blood glucose level increases, after a meal, the release of insulin into, blood increases rapidly. Within few minutes,, concentration of insulin in plasma increases up, to 100 µU/mL from the basal level of 10 µU/mL., It is because of release of insulin that is stored, in pancreas. Later, within 10 to 15 minutes, the, insulin concentration in the blood reduces to half, the value, i.e. up to 40 to 50 µU/mL of plasma.
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418 Section 6 t Endocrinology, ii. After 15 to 20 minutes, the insulin secretion rises, once again. This time it rises slowly but steadily., It reaches the maximum between 2 and 2½, hours. The prolonged increase in insulin release, is due to the formation of new insulin molecules, continuously from pancreas (Fig. 69.2)., , All these diabetogenic hormones increase the blood, glucose level, which stimulates β-cells of islets of, Langerhans. So insulin secretion is increased., Prolonged hypersecretion of these hormones causes, exhaustion of β-cells, resulting in diabetes mellitus., 6. Role of Autonomic Nerves, , 2. Role of Proteins, Excess amino acids in blood also stimulate insulin, secretion. Potent amino acids are arginine and lysin., Without any increase in blood glucose level, the amino, acids alone can cause a slight increase in insulin, secretion. However, amino acids potentiate the action, of glucose on insulin secretion so that, in the presence, of amino acids, elevated blood glucose level increases, insulin secretion to a great extent., 3. Role of Lipid Derivatives, The β-ketoacids such as acetoacetate also increase, insulin secretion., 4. Role of Gastrointestinal Hormones, Insulin secretion is increased by some of the, gastrointestinal hormones such as gastrin, secretin,, CCK and GIP., 5. Role of Endocrine Hormones, Diabetogenic hormones like glucagon, growth hormone, and cortisol also stimulate insulin secretion, indirectly., , Stimulation of parasympathetic nerve to the pancreas, (right vagus) increases insulin secretion. Chemical, neurotransmitter involved is acetylcholine. Stimulation, of sympathetic nerves inhibits the secretion of insulin, and the neurotransmitter is noradrenaline., However, the role of these nerves on the regulation, of insulin secretion under physiological conditions is not, clear., , GLUCAGON, SOURCE OF SECRETION, Glucagon is secreted from A cells or α-cells in the islets, of Langerhans of pancreas. It is also secreted from A, cells of stomach and L cells of intestine., CHEMISTRY AND HALF-LIFE, Glucagon is a polypeptide with a molecular weight of, 3,485. It contains 29 amino acids. Half-life of glucagon, is 3 to 6 minutes., SYNTHESIS, Glucagon is synthesized from the preprohormone, precursor called preproglucagon in the α-cells of islets., Preproglucagon is converted into proglucagon, which, gives rise to glucagon., METABOLISM, About 30% of glucagon is degraded in liver and 20% in, kidney. The cleaved glucagon fragments are excreted, through urine. 50% of the circulating glucagon is, degraded in blood itself by enzymes such as serine and, cysteine proteases., , ACTIONS OF GLUCAGON, Actions of glucagon are antagonistic to those of insulin, (Table 69.1). It increases the blood glucose level,, peripheral utilization of lipids and the conversion of, proteins into glucose., 1. On Carbohydrate Metabolism, FIGURE 69.2: Changes in plasma level of insulin after meals., Increase in blood glucose level after meals produces biphasic, effect on plasma level of insulin., , Glucagon increases the blood glucose level by:, i. Increasing glycogenolysis in liver and releasing, glucose from the liver cells into the blood.
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Chapter 69 t Endocrine Functions of Pancreas 419, TABLE 69.1: Differences between insulin and glucagon, Features, , Insulin, , Glucagon, , Source of secretion, , β-cells of islets of langerhans, , α-cells of islets of langerhans, , Action on carbohydrate, metabolism, , Decreases blood glucose level by:, 1. Facilitating transport and uptake of glucose, by all cells except liver cells, 2. Increasing peripheral utilization of glucose, 3. Increasing glycogenesis in liver and muscle, 4. Preventing glycogenolysis, 5. Preventing gluconeogenesis, , Increases blood glucose level by:, 1. Facilitating glucose transport into liver cells, 2. Increasing glycogenolysis, 3. Increasing gluconeogenesis, , Action on protein, metabolism, , 1. Facilitates amino acid transport, 2. Accelerates protein synthesis, 3. Prevents protein catabolism, 4. Prevents conversion of proteins into glucose, , 1. Increases transport of amino acids into liver, cells, 2. Increases utilization of amino acids for, gluconeogenesis, , Action on fat, metabolism, , 1. Increases synthesis and storage of fat, 2. No ketogenic effect, , 1. Increases lipolysis, 2. Promotes ketogenesis, , Blood fatty acids, , Decreases, , Increases, , Hypersecretion leads to, , Hypoglycemia, , Hyperglycemia, , Hyposecretion leads to, , Diabetes mellitus, , Hypoglycemia, , Glucagon does not induce glycogenolysis in, muscle, ii. Increasing gluconeogenesis in liver by:, a. Activating the enzymes, which convert, pyruvate into phosphoenol pyruvate, b. Increasing the transport of amino acids into, the liver cells. The amino acids are utilized, for glucose formation., , via G protein. Adenyl cyclase causes the formation of, cyclic adenosine monophosphate (AMP) which brings, out the actions of glucagon. Glucagon receptor is a, peptide with a molecular weight of 62,000., REGULATION OF GLUCAGON SECRETION, Secretion of glucagon is controlled mainly by glucose, and amino acid levels in the blood., , 2. On Protein Metabolism, , 1. Role of Blood Glucose Level, , Glucagon increases the transport of amino acids into liver, cells. The amino acids are utilized for gluconeogenesis., , Important factor that regulates the secretion of glucagon, is the decrease in blood glucose level. When blood, glucose level decreases below 80 mg/dL of blood,, α-cells of islets of Langerhans are stimulated and more, glucagon is released. Glucagon, in turn increases the, blood glucose level. On the other hand, when blood, glucose level increases, α-cells are inhibited and the, secretion of glucagon decreases., , 3. On Fat Metabolism, Glucagon shows lipolytic and ketogenic actions. It, increases lipolysis by increasing the release of free fatty, acids from adipose tissue and making them available for, peripheral utilization. The lipolytic activity of glucagon, in, turn promotes ketogenesis (formation of ketone bodies), in liver., 4. Other Actions, Glucagon:, i. Inhibits the secretion of gastric juice, ii. Increases the secretion of bile from liver., , 2. Role of Amino Acid Level in Blood, Increase in amino acid level in blood stimulates the, secretion of glucagon. Glucagon, in turn converts the, amino acids into glucose., 3. Role of Other Factors, Factors which increase glucagon secretion:, , MODE OF ACTION OF GLUCAGON, On the target cells (mostly liver cells), glucagon, combines with receptor and activates adenyl cyclase, , i. Exercise, ii. Stress, iii. Gastrin
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420 Section 6 t Endocrinology, iv. Cholecystokinin (CCK), v. Cortisol., Factors which inhibit glucagon secretion:, i., ii., iii., iv., , Somatostatin, Insulin, Free fatty acids, Ketones., , SOMATOSTATIN, SOURCE OF SECRETION, Somatostatin is secreted from:, 1. Hypothalamus, 2. D cells (δ-cells) in islets of Langerhans of pancreas, 3. D cells in stomach and upper part of small, intestine., CHEMISTRY AND HALF-LIFE, Somatostatin is a polypeptide. It is synthesized in two, forms, namely somatostatin-14 (with 14 amino acids), and somatostatin-28 (with 28 amino acids). Both the, forms have similar actions. Half-life of somatostatin is, 2 to 4 minutes., SYNTHESIS, Somatostatin is synthesized from the precursor, prosomatostatin. Prosomatostatin is converted mostly, into somatostatin-14 in the D cells of islets in pancreas., However, in the intestine, large amount of somatostatin28 is produced from prosomatostatin., METABOLISM, , REGULATION OF SECRETION, OF SOMATOSTATIN, Pancreatic Somatostatin, Secretion of pancreatic somatostatin is stimulated, by glucose, amino acids and CCK. The tumor of D, cells of islets of Langerhans causes hypersecretion, of somatostatin. It leads to hyperglycemia and other, symptoms of diabetes mellitus., Gastrointestinal Tract Somatostatin, Secretion of somatostatin in GI tract is increased by the, presence of chyme-containing glucose and proteins in, stomach and small intestine., , PANCREATIC POLYPEPTIDE, SOURCE OF SECRETION, Pancreatic polypeptide is secreted by F cells or PP cells, in the islets of Langerhans of pancreas. It is also found, in small intestine., CHEMISTRY AND HALF-LIFE, Pancreatic polypeptide is a polypeptide with 36 amino, acids. Its half-life is 5 minutes., SYNTHESIS, Pancreatic polypeptide is synthesized from preprohormone precursor called prepropancreatic polypeptide in the PP cells of islets., METABOLISM, , Somatostatin is degraded in liver and kidney., , Pancreatic polypeptide is degraded and removed from, circulation mainly in kidney., , ACTIONS OF SOMATOSTATIN, , ACTIONS OF PANCREATIC POLYPEPTIDE, , 1. Somatostatin acts within islets of Langerhans and,, inhibits β and α cells, i.e. it inhibits the secretion of, both glucagon and insulin, 2. It decreases the motility of stomach, duodenum and, gallbladder, 3. It reduces the secretion of gastrointestinal hormones, gastrin, CCK, GIP and VIP, 4. Hypothalamic somatostatin inhibits the secretion of GH, and TSH from anterior pituitary. That is why, it is also, called growth hormone-inhibitory hormone (GHIH)., MODE OF ACTION OF SOMATOSTATIN, Somatostatin brings out its actions through cAMP., , Exact physiological action of pancreatic polypeptide is, not known. It is believed to increase the secretion of, glucagon from α-cells in islets of Langerhans., MODE OF ACTION OF, PANCREATIC POLYPEPTIDE, Pancreatic polypeptide brings out its actions through, cAMP., REGULATION OF SECRETION, Secretion of pancreatic polypeptide is stimulated by, the presence of chyme containing more proteins in the, small intestine.
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Chapter 69 t Endocrine Functions of Pancreas 421, , REGULATION OF BLOOD GLUCOSE, LEVEL (BLOOD GLUCOSE LEVEL), , ROLE OF OTHER HORMONES IN THE, MAINTENANCE OF BLOOD GLUCOSE LEVEL, , NORMAL BLOOD GLUCOSE LEVEL, , Other hormones which increase the blood glucose level, are:, 1. Growth hormone (Chapter 66), 2. Thyroxine (Chapter 67), 3. Cortisol (Chapter 70), 4. Adrenaline (Chapter 71)., Thus, liver helps to maintain the blood glucose, level by storing glycogen when blood glucose level, is high after meals; and by releasing glucose, when, blood glucose level is low after 2 to 3 hours of food, intake. Insulin helps to control the blood glucose level,, especially after meals, when it increases. Glucagon and, other hormones help to maintain the blood glucose level, by raising it in between the meals., , In normal persons, blood glucose level is controlled, within a narrow range. In the early morning after, overnight fasting, the blood glucose level is low ranging, between 70 and 110 mg/dL of blood. Between first, and second hour after meals (postprandial), the blood, glucose level rises to 100 to 140 mg/dL. Glucose level, in blood is brought back to normal at the end of second, hour after the meals., Blood glucose regulating mechanism is operated, through liver and muscle by the influence of the, pancreatic hormones – insulin and glucagon. Many, other hormones are also involved in the regulation of, blood glucose level. Among all the hormones, insulin is, the only hormone that reduces the blood glucose level, and it is called the antidiabetogenic hormone. The, hormones which increase blood glucose level are called, diabetogenic hormones or anti-insulin hormones., Necessity of Regulation of Blood Glucose Level, Regulation of blood glucose (sugar) level is very essential, because, glucose is the only nutrient that is utilized for, energy by many tissues such as brain tissues, retina, and germinal epithelium of the gonads., ROLE OF LIVER IN THE MAINTENANCE, OF BLOOD GLUCOSE LEVEL, , APPLIED PHYSIOLOGY, HYPOACTIVITY – DIABETES MELLITUS, Diabetes mellitus is a metabolic disorder characterized, by high blood glucose level, associated with other, manifestations. ‘Diabetes’ means ‘polyuria’ and, ‘mellitus’ means ‘honey’. The name ‘diabetes mellitus’, was coined by Thomas Willis, who discovered sweetness, of urine from diabetics in 1675., In most of the cases, diabetes mellitus develops, due to deficiency of insulin., Classification of Diabetes Mellitus, , Liver serves as an important glucose buffer system., When blood glucose level increases after a meal, the, excess glucose is converted into glycogen and stored, in liver. Afterwards, when blood glucose level falls, the, glycogen in liver is converted into glucose and released, into the blood. The storage of glycogen and release of, glucose from liver are mainly regulated by insulin and, glucagon., , There are several forms of diabetes mellitus, which, occur due to different causes. Diabetes may be primary, or secondary. Primary diabetes is unrelated to another, disease. Secondary diabetes occurs due to damage or, disease of pancreas by another disease or factor., Recent classification divides primary diabetes, mellitus into two types, Type I and Type II. Differences, between the two types are given in Table 69.2., , ROLE OF INSULIN IN THE MAINTENANCE, OF BLOOD GLUCOSE LEVEL, , Type I Diabetes Mellitus, , Insulin decreases the blood glucose level and it is the, only antidiabetic hormone available in the body (Refer, the actions of insulin on carbohydrate metabolism in this, Chapter)., ROLE OF GLUCAGON IN THE MAINTENANCE, OF BLOOD GLUCOSE LEVEL, Glucagon increases the blood glucose level (Refer, actions of glucagon on carbohydrate metabolism in this, Chapter)., , Type I diabetes mellitus is due to deficiency of insulin, because of destruction of β-cells in islets of Langerhans., This type of diabetes mellitus may occur at any age of, life. But, it usually occurs before 40 years of age and, the persons affected by this require insulin injection., So it is also called insulin-dependent diabetes mellitus, (IDDM). When it develops at infancy or childhood, it is, called juvenile diabetes., Type I diabetes mellitus develops rapidly and progresses at a rapid phase. It is not associated with obesity,, but may be associated with acidosis or ketosis.
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422 Section 6 t Endocrinology, Causes of type I diabetes mellitus, , Type II diabetes mellitus may or may not be, associated with ketosis, but often it is associated with, obesity., , 1. Degeneration of β-cells in the islets of Langerhans, of pancreas, 2. Destruction of β-cells by viral infection, 3. Congenital disorder of β-cells, 4. Destruction of β-cells during autoimmune diseases., It is due to the development of antibodies against, β-cells (Refer Chapter 17 for details)., , Causes for type II diabetes mellitus, In this type of diabetes, the structure and function of, β-cells and blood level of insulin are normal. But insulin, receptors may be less, absent or abnormal, resulting in, insulin resistance., Common causes of insulin resistance are:, 1. Genetic disorders (significant factors causing type II, diabetes mellitus), 2. Lifestyle changes such as bad eating habits and, physical inactivity, leading to obesity, 3. Stress., , Other forms of type 1 diabetes mellitus, 1. Latent autoimmune diabetes in adults (LADA):, LADA or slow onset diabetes has slow onset and, slow progress than IDDM and it occurs in later life, after 35 years. It may be difficult to distinguish LADA, from type II diabetes mellitus, since pancreas takes, longer period to stop secreting insulin., 2. Maturity onset diabetes in young individuals, (MODY): It is a rare inherited form of diabetes, mellitus that occurs before 25 years. It is due to, hereditary defects in insulin secretion., , Other forms of type II diabetes mellitus, 1. Gestational diabetes: It occurs during pregnancy. It, is due to many factors such as hormones secreted, during pregnancy, obesity and lifestyle before and, during pregnancy. Usually, diabetes disappears, after delivery of the child. However, the woman, has high risk of development of type II diabetes, later., 2. Pre-diabetes: It is also called chemical, subclinical,, latent or borderline diabetes. It is the stage between, normal condition and diabetes. The person does not, show overt (observable) symptoms of diabetes but, there is an increase in blood glucose level. Though, pre-diabetes is reversible, the affected persons are, at a high risk of developing type II diabetes mellitus., , Type II Diabetes Mellitus, Type II diabetes mellitus is due to insulin resistance, (failure of insulin receptors to give response to insulin)., So, the body is unable to use insulin. About 90% of, diabetic patients have type II diabetes mellitus. It usually, occurs after 40 years. Only some forms of Type II diabetes, require insulin. In most cases, it can be controlled by, oral hypoglycemic drugs. So it is also called noninsulindependent diabetes mellitus (NIDDM)., , TABLE 69.2: Differences between type I and type II diabetes mellitus, Features, , Type I (IDDM), , Type II (NIDDM), , Age of onset, , Usually before 40 year, , Usually after 40 year, , Major cause, , Lack of insulin, , Lack of insulin receptor, , Insulin deficiency, , Yes, , Partial deficiency, , Immune destruction of β-cells, , Yes, , No, , Involvement of other endocrine disorders, , No, , Yes, , Hereditary cause, , Yes, , May or may not be, , Need for insulin, , Always, , Not in initial stage, May require in later stage, , Insulin resistance, , No, , Yes, , Control by oral hypoglycemic agents, , No, , Yes, , Symptoms appear, , Rapidly, , Slowly, , Body weight, , Usually thin, , Usually overweight, , Stress-induced obesity, , No, , Yes, , Ketosis, , Yes, , May or may not be
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Chapter 69 t Endocrine Functions of Pancreas 423, Secondary Diabetes Mellitus, , 3. Polyuria, , Secondary diabetes mellitus is rare and only about 2%, of diabetic patients have secondary diabetes. It may, be temporary or may become permanent due to the, underlying cause., , Excess urine formation with increase in the frequency of, voiding urine is called polyuria. It is due to the osmotic, diuresis caused by increase in blood glucose level., , Causes of secondary diabetes mellitus, , Increase in water intake is called polydipsia. Excess, loss of water decreases the water content and increases, the salt content in the body. This stimulates the thirst, center in hypothalamus. Thirst center, in turn increases, the intake of water., , 1. Endocrine disorders such as gigantism, acromegaly, and Cushing’s syndrome., Hyperglycemia in these conditions causes excess, stimulation of β-cells. Constant and excess stimulation, in turn causes burning out and degeneration of, β-cells. The β-cell exhaustion leads to permanent, diabetes mellitus., 2. Damage of pancreas due to disorders such as chronic, pancreatitis, cystic fibrosis and hemochromatosis, (high iron content in body causing damage of, organs), 3. Pancreatectomy (surgical removal), 4. Liver diseases such as hepatitis C and fatty liver, 5. Autoimmune diseases such as celiac disease, 6. Excessive use of drugs like antihypertensive, drugs (beta blockers and diuretics), steroids, oral, contraceptives, chemotherapy drugs, etc., 7. Excessive intake of alcohol and opiates., Signs and Symptoms of Diabetes Mellitus, Various manifestations of diabetes mellitus develop, because of three major setbacks of insulin deficiency., 1. Increased blood glucose level (300 to 400 mg/dL), due to reduced utilization by tissue, 2. Mobilization of fats from adipose tissue for energy, purpose, leading to elevated fatty acid content in, blood. This causes deposition of fat on the wall of, arteries and development of atherosclerosis, 3. Depletion of proteins from the tissues., Following are the signs and symptoms of diabetes, mellitus:, 1. Glucosuria, , 4. Polydipsia, , 5. Polyphagia, Polyphagia means the intake of excess food. It is very, common in diabetes mellitus., 6. Asthenia, Loss of strength is called asthenia. Body becomes very, weak because of this. Asthenia occurs due to protein, depletion, which is caused by lack of insulin. Lack of insulin, causes decrease in protein synthesis and increase in, protein breakdown, resulting in protein depletion. Protein, depletion also occurs due to the utilization of proteins for, energy in the absence of glucose utilization., 7. Acidosis, During insulin deficiency, glucose cannot be utilized by, the peripheral tissues for energy. So, a large amount, of fat is broken down to release energy. It causes the, formation of excess ketoacids, leading to acidosis., One more reason for acidosis is that the ketoacids, are excreted in combination with sodium ions through, urine (ketonuria). Sodium is exchanged for hydrogen, ions, which diffuse from the renal tubules into ECF, adding to acidosis., 8. Acetone breathing, In cases of severe ketoacidosis, acetone is expired in, the expiratory air, giving the characteristic acetone or, fruity breath odor. It is a life-threatening condition of, severe diabetes., , Glucosuria is the loss of glucose in urine. Normally,, glucose does not appear in urine. When glucose level, rises above 180 mg/dL in blood, glucose appears in, urine. It is the renal threshold level for glucose., , 9. Kussmaul breathing, , 2. Osmotic diuresis, , Osmotic diuresis leads to dehydration, which causes, circulatory shock. It occurs only in severe diabetes., , Osmotic diuresis is the diuresis caused by osmotic, effects. Excess glucose in the renal tubules develops, osmotic effect. Osmotic effect decreases the reabsorption of water from renal tubules, resulting in, diuresis. It leads to polyuria and polydipsia., , Kussmaul breathing is the increase in rate and depth of, respiration caused by severe acidosis., 10. Circulatory shock, , 11. Coma, Due to Kussmaul breathing, large amount of carbon, dioxide is lost during expiration. It leads to drastic
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424 Section 6 t Endocrinology, reduction in the concentration of bicarbonate ions, causing severe acidosis and coma. It occurs in severe, cases of diabetes mellitus., Increase in the blood glucose level develops, hyperosmolarity of plasma which also leads to coma. It, is called hyperosmolar coma., Complications of Diabetes Mellitus, Prolonged hyperglycemia in diabetes mellitus causes, dysfunction and injury of many tissues, resulting in some, complications. Development of these complications, is directly proportional to the degree and duration, of hyperglycemia. However, the patients with wellcontrolled diabetes can postpone the onset or reduce, the rate of progression of these complications., Initially, the untreated chronic hyperglycemia affects, the blood vessels, resulting in vascular complications, like atherosclerosis. Vascular complications are responsible for the development of most of the complications, of diabetes such as:, 1. Cardiovascular complications like:, i. Hypertension, ii. Myocardial infarction, 2. Degenerative changes in retina called diabetic, retinopathy, 3. Degenerative changes in kidney known as diabetic, nephropathy, 4. Degeneration of autonomic and peripheral nerves, called diabetic neuropathy., , tract if taken orally. So, it is generally administered by, subcutaneous injection., Type II diabetes mellitus, Type II diabetes mellitus is treated by oral hypoglycemic, drugs. Patients with longstanding severe diabetes, mellitus may require a combination of oral hypoglycemic, drugs with insulin to control the hyperglycemia., Oral hypoglycemic drugs are classified into three, types., 1. Insulin secretagogues: These drugs decrease the, blood glucose level by stimulating insulin secretion, from β-cells. Sulfonylureas (tolbutamide, gluburide,, glipizide, etc.) are the commonly available insulin, secretagogues, 2. Insulin sensitizers: These drugs decrease the, blood glucose level by facilitating the insulin action, in the target tissues. Examples are biguanides, (metformin) and thiazolidinediones (pioglitazone, and rosiglitazone), 3. Alpha glucosidase inhibitors: These drugs control, blood glucose level by inhibiting α-glucosidase. This, intestinal enzyme is responsible for the conversion, of dietary and other complex carbohydrates into, glucose and other monosaccharides, which can be, absorbed from intestine. Examples of α-glucosidase, inhibitors are acarbose and meglitol., HYPERACTIVITY – HYPERINSULINISM, , Diagnostic Tests for Diabetes Mellitus, Diagnosis of diabetes mellitus includes the determination, of:, 1. Fasting blood glucose, 2. Postprandial blood glucose, 3. Glucose tolerance test (GTT), 4. Glycosylated (glycated) hemoglobin., Determination of glycosylated hemoglobin is, commonly done to monitor the glycemic control of the, persons already diagnosed with diabetes mellitus., , Hyperinsulinism is the hypersecretion of insulin., Cause of Hyperinsulinism, Hyperinsulinism occurs due to the tumor of β-cells in the, islets of Langerhans., Signs and Symptoms of Hyperinsulinism, 1. Hypoglycemia, , Abnormal response in diagnostic tests, , Blood glucose level falls below 50 mg/dL., , Abnormal response in diagnostic tests occurs in, conditions like pre-diabetes (see above). There is, an increased fasting blood glucose level or impaired, (decreased) glucose tolerance., , 2. Manifestations of central nervous system, , Treatment for Diabetes Mellitus, Type I diabetes mellitus, Type I diabetes mellitus is treated by exogenous insulin., Since insulin is a polypeptide, it is degraded in GI, , Manifestations of central nervous system occur when, the blood glucose level decreases. All the manifestations, are together called neuroglycopenic symptoms., Initially, the activity of neurons increases, resulting, in nervousness, tremor all over the body and sweating., If not treated immediately, it leads to clonic convulsions, and unconsciousness. Slowly, the convulsions cease, and coma occurs due to the damage of neurons.
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Adrenal Cortex, , , , , , , , , , , , Chapter, , 70, , IMPORTANCE OF ADRENAL GLANDS, FUNCTIONAL ANATOMY, HISTOLOGY OF ADRENAL CORTEX, HORMONES, SYNTHESIS, TRANSPORT AND FATE OF ADRENOCORTICAL HORMONES, MINERALOCORTICOIDS, GLUCOCORTICOIDS, ADRENAL SEX HORMONES, EXOGENOUS STEROIDS, APPLIED PHYSIOLOGY, , IMPORTANCE OF ADRENAL GLANDS, Adrenal glands are called the ‘life-saving glands’ or, ‘essential endocrine glands’. It is because the absence, of adrenocortical hormones causes death within 3 to, 15 days and absence of adrenomedullary hormones,, drastically decreases the resistance to mental and, physical stress., , FUNCTIONAL ANATOMY, OF ADRENAL GLANDS, There are two adrenal glands. Each gland is situated on, the upper pole of each kidney. Because of the situation,, adrenal glands are otherwise called suprarenal glands., Each gland weighs about 4 g., , functions resemble that of sympathetic nervous system., Adrenal cortex develops from the mesonephros, which, give rise to the renal tissues. It secretes entirely a, different group of hormones known as corticosteroids., , HISTOLOGY OF ADRENAL CORTEX, Adrenal cortex is formed by three layers of structure., Each layer is distinct from one another., 1. Outer zona glomerulosa, 2. Middle zona fasciculata, 3. Inner zona reticularis., , PARTS OF ADRENAL GLAND, Adrenal gland (Fig. 70.1) is made of two distinct parts:, 1. Adrenal cortex: Outer portion, constituting 80% of, the gland, 2. Adrenal medulla: Central portion, constituting 20%, of the gland., These two parts are different from each other in, development, structure and functions. Adrenal medulla, develops from the neural crest, which gives origin to, sympathetic nervous system. So, its secretions and, , FIGURE 70.1: Adrenal gland
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426 Section 6 t Endocrinology, , HORMONES OF ADRENAL CORTEX, Adrenocortical hormones are steroids in nature, hence, the name ‘corticosteroids’. Based on their functions,, corticosteroids are classified into three groups:, 1. Mineralocorticoids, 2. Glucocorticoids, 3. Sex hormones., , SYNTHESIS, TRANSPORT AND FATE, OF ADRENOCORTICAL HORMONES, SYNTHESIS, All adrenocortical hormones are steroid in nature and, are synthesized mainly from cholesterol that is absorbed, directly from the circulating blood. Small quantity of, cholesterol is also synthesized within the cortical cells, from acetylcoenzyme A (acetyl-CoA). Synthesis of, aldosterone is given in Fig. 70.2., TRANSPORT, Mineralocorticoids, , are found free in plasma. Albumin plays a very little role, in glucocorticoid transport., Sex Hormones, Adrenal sex hormones are transported by another, special plasma protein known as sex hormone-binding, globulin., , FATE OF CORTICOSTEROIDS, Corticosteroids are degraded mainly in the liver and, conjugated to form glucuronides and to a lesser extent,, form sulfates. About 25% of corticosteroids are excreted, in bile and feces and remaining 75%, in the urine., , MINERALOCORTICOIDS, Mineralocorticoids are the corticosteroids that act on, the minerals (electrolytes), particularly sodium and, potassium., Mineralocorticoids are:, 1. Aldosterone, 2. 11-deoxycorticosterone., , Mineralocorticoids are transported in blood by binding, with plasma proteins, especially globulins. The binding, is loose and 50% of these hormones are present in free, form., , SOURCE OF SECRETION, , Glucocorticoids, , CHEMISTRY AND HALF-LIFE, , Glucocorticoids are transported by a special plasma, protein known as glucocorticoids-binding globulin or, transcortin. Ninety four percent of glucocorticoids are, transported by this protein, whereas about 6% of them, , Mineralocorticoids are C21 steroids having 21 carbon, atoms. Half-life of mineralocorticoids is 20 minutes., , Mineralocorticoids are secreted by zona glomerulosa of, adrenal cortex., , DAILY OUTPUT AND PLASMA LEVEL, Daily output and plasma level of mineralocorticoids are, given in Table 70.1., FUNCTIONS OF MINERALOCORTICOIDS, Ninety percent of mineralocorticoid activity is provided, by aldosterone., Life-saving Hormone, Aldosterone is very essential for life and it maintains, the osmolarity and volume of ECF. It is usually called, TABLE 70.1: Daily output and plasma level, of mineralocorticoids, Daily output, (µg), , Plasma level, (µg/dL), , Aldosterone, , 0.15, , 0.006, , 11-Deoxycorticosterone, , 0.2, , 0.006, , Hormone, , FIGURE 70.2: Synthesis of aldosterone
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Chapter 70 t Adrenal Cortex 427, life-saving hormone because, its absence causes, death within 3 days to 2 weeks. Aldosterone has three, important functions., It increases:, 1. Reabsorption of sodium from renal tubules, 2. Excretion of potassium through renal tubules, 3. Secretion of hydrogen into renal tubules., Actions of aldosterone are:, 1. On Sodium Ions, Aldosterone acts on the distal convoluted tubule and, the collecting duct and increases the reabsorption of, sodium. During hypersecretion of aldosterone, the loss, of sodium through urine is only few milligram per day., But during hyposecretion of aldosterone, the loss of, sodium through urine increases (hypernatriuria) up to, about 20 g/day. It proves the importance of aldosterone, in regulation of sodium ion concentration and osmolality, in the body., 2. On Extracellular Fluid Volume, When sodium ions are reabsorbed from the renal, tubules, simultaneously water is also reabsorbed. Water, reabsorption is almost equal to sodium reabsorption; so, the net result is the increase in ECF volume., Even though aldosterone increases the sodium, reabsorption from renal tubules, the concentration, of sodium in the body does not increase very much, because water is also reabsorbed simultaneously., But still, there is a possibility for mild increase in, concentration of sodium in blood (mild hypernatremia)., It induces thirst, leading to intake of water which again, increases the ECF volume and blood volume., , ANP causes excretion of sodium in spite of, increase in aldosterone secretion, ii. It causes pressure diuresis (excretion of excess, salt and water by high blood pressure) through, urine. This decreases the salt and water content, in ECF, in spite of hypersecretion of aldosterone, (Fig. 70.3)., Besides ANP, two more natriuretic peptides called, brain natriuretic peptide (BNP) and C-type natriuretic, peptide (CNP) are also secreted by cardiac muscle, (Chapter 72). BNP and CNP also have similar actions of, ANP on sodium excretion., Significance of aldosterone escape, Because of aldosterone escape, edema does not occur., 4. On Potassium Ions, Aldosterone increases the potassium excretion through, the renal tubules. When aldosterone is deficient, the, potassium ion concentration in ECF increases leading to, hyperkalemia. Hyperkalemia results in serious cardiac, toxicity, with weak contractions of heart and development, of arrhythmia. In very severe conditions, it may cause, cardiac death. When aldosterone secretion increases, it, leads to hypokalemia and muscular weakness., 5. On Hydrogen Ion Concentration, While increasing the sodium reabsorption from renal, tubules, aldosterone causes tubular secretion of hydro-, , 3. On Blood Pressure, Increase in ECF volume and the blood volume finally, leads to increase in blood pressure., Aldosterone escape or escape phenomenon, Aldosterone escape refers to escape of the kidney, from salt-retaining effects of excess administration, or secretion of aldosterone, as in the case of primary, hyperaldosteronism., Mechanism of aldosterone escape, When aldosterone level increases, there is excess, retention of sodium and water. This increases the volume, of ECF and blood pressure. Aldosterone-induced high, blood pressure decreases the ECF volume through two, types of reactions:, i. It stimulates secretion of atrial natriuretic, peptide (ANP) from atrial muscles of the heart:, , FIGURE 70.3: Aldosterone escape
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428 Section 6 t Endocrinology, gen ions. To some extent, secretion of hydrogen ions, is in exchange for sodium ions. It obviously reduces, the hydrogen ion concentration in the ECF. In normal, conditions, aldosterone is essential to maintain acidbase balance in the body. In hypersecretion, it causes, alkalosis and in hyposecretion, it causes acidosis., 6. On Sweat Glands and Salivary Glands, Aldosterone has almost the similar effect on sweat, glands and salivary glands as it shows on renal tubules., Sodium is reabsorbed from sweat glands under the, influence of aldosterone, thus the loss of sodium from, the body is prevented. Same effect is shown on saliva, also. Thus, aldosterone helps in the conservation of, sodium in the body., , Sequence of Events, 1. Since aldosterone is lipid soluble, it diffuses readily, into the cytoplasm of the tubular epithelial cells, through the lipid layer of the cell membrane, 2. In the cytoplasm, aldosterone binds with the specific, receptor protein, 3. Aldosterone-receptor complex diffuses into the, nucleus where it binds to deoxyribonucleic acid, (DNA) and causes formation of mRNA, 4. The mRNA diffuses back into the cytoplasm and, causes protein synthesis along with ribosomes., Most of the synthesized proteins are in the form, of enzymes. One of such enzymes is sodiumpotassium ATPase, which helps in the transport of, sodium and potassium., REGULATION OF SECRETION, , 7. On Intestine, Aldosterone increases sodium absorption from the, intestine, especially from colon and prevents loss of, sodium through feces. Aldosterone deficiency leads to, diarrhea, with loss of sodium and water., MODE OF ACTION, Aldosterone acts through the messenger RNA (mRNA), mechanism., , Aldosterone secretion is regulated by four important, factors (Fig. 70.4) which are given below in the order of, their potency:, 1. Increase in potassium ion (K+) concentration in ECF, 2. Decrease in sodium ion (Na+) concentration in ECF, 3. Decrease in ECF volume, 4. Adrenocorticotropic hormone (ACTH)., Increase in the concentration of potassium ions is, the most effective stimulant for aldosterone secretion., , FIGURE 70.4: Importance of aldosterone. ECF = Extracellular fluid.
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Chapter 70 t Adrenal Cortex 429, It acts directly on the zona glomerulosa and increases, the secretion of aldosterone. Decrease in sodium ion, concentration and ECF volume stimulates aldosterone, secretion through renin-angiotensin mechanism. Renin, secreted from juxtaglomerular apparatus of kidney acts, on angiotensinogen in the plasma and converts it into, angiotensin I, which is converted into angiotensin II by, converting enzyme (ACE) secreted by lungs. Angiotensin, II acts on the zona glomerulosa to secrete more, aldosterone. Aldosterone in turn, increases the retention, of sodium and water and excretion of potassium. This, leads to increase in the sodium ion concentration and, ECF volume., Now, the increased sodium ion concentration and, the ECF volume inhibit the juxtaglomerular apparatus, and stop the release of renin. So, angiotensin II is not, formed and release of aldosterone from adrenal cortex, is stopped (Fig. 70.5)., Adrenocorticotropic hormone mainly stimulates, the secretion of glucocorticoids. It has only a mild, stimulating effect on aldosterone secretion., , SOURCE OF SECRETION, Glucocorticoids are secreted mainly by zona fasciculata, of adrenal cortex. A small quantity of glucocorticoids is, also secreted by zona reticularis. Synthesis of cortisol is, given in Fig. 70.6., CHEMISTRY AND HALF-LIFE, Glucocorticoids are C21 steroids having 21 carbon, atoms. Half-life of cortisol is 70 to 90 minutes and that, of corticosterone is 50 minutes. Half-life of cortisone is, not known., DAILY OUTPUT AND PLASMA LEVEL, Daily output and plasma level of glucocorticoids are, given in Table 70.2., FUNCTIONS OF GLUCOCORTICOIDS, Cortisol or hydrocortisone is more potent and it has 95%, of glucocorticoid activity. Corticosterone is less potent,, TABLE 70.2: Daily output and plasma level, of glucocorticoids, , GLUCOCORTICOIDS, Glucocorticoids act mainly on glucose metabolism., Glucocorticoids are:, 1. Cortisol, 2. Corticosterone, 3. Cortisone., , Hormone, Cortisol, Corticosterone, , FIGURE 70.5: Regulation of aldosterone secretion, , Daily output, (µg), , Plasma level, (µg/dL), , 10.0, , 13.9, , 3.0, , 0.4
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430 Section 6 t Endocrinology, , FIGURE 70.6: Synthesis of cortisol, , showing only 4% of glucocorticoid activity. Cortisone, with 1% activity is secreted in minute quantity., , these hormones causes hypoglycemia and fasting, during adrenal insufficiency will be fatal. It decreases, blood glucose level to a great extent, resulting in death., , Life-protecting Hormone, Like aldosterone, cortisol is also essential for life but in, a different way. Aldosterone is a life-saving hormone,, whereas cortisol is a life-protecting hormone because, it, helps to withstand the stress and trauma in life., Glucocorticoids have metabolic effects on, carbohydrates, proteins, fats and water. These hormones, also show mild mineralocorticoid effect. Removal of, adrenal glands in human beings and animals causes, disturbances of metabolism. Exposure to even mild, harmful stress after adrenalectomy, leads to collapse, and death., 1. On Carbohydrate Metabolism, Glucocorticoids increase the blood glucose level by two, ways:, i. By promoting gluconeogenesis in liver from, amino acids: Glucocorticoids enhance the, breakdown of proteins in extrahepatic cells,, particularly the muscle. It is followed by release, of amino acids into circulation. From blood,, amino acids enter the liver and get converted, into glucose (gluconeogenesis), ii. By inhibiting the uptake and utilization of glucose, by peripheral cells: This action is called antiinsulin action of glucocorticoids., Hypersecretion of glucocorticoids increases, the blood glucose level, resulting in hyperglycemia,, glucosuria and adrenal diabetes. Hyposecretion of, , 2. On Protein Metabolism, Glucocorticoids promote the catabolism of proteins,, leading to:, i. Decrease in cellular proteins, ii. Increase in plasma level of amino acids, iii. Increase in protein content in liver., Glucocorticoids cause catabolism of proteins by the, following methods:, i. By releasing amino acids from body cells (except, liver cells), into the blood, ii. By increasing the uptake of amino acids by, hepatic cells from blood. In hepatic cells, the, amino acids are used for the synthesis of, proteins and carbohydrates (gluconeogenesis)., Thus, glucocorticoids cause mobilization of proteins, from tissues other than liver. In hypersecretion of, glucocorticoids, there is excess catabolism of proteins,, resulting in muscular wasting and negative nitrogen, balance., , 3. On Fat Metabolism, Glucocorticoids cause mobilization and redistribution of, fats. Actions on fats are:, i. Mobilization of fatty acids from adipose tissue, ii. Increasing the concentration of fatty acids in, blood, iii. Increasing the utilization of fat for energy.
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Chapter 70 t Adrenal Cortex 431, Glucocorticoids decrease the utilization of glucose., At the same time, these hormones mobilize fats and, make the fatty acids available for utilization, by which, energy is liberated. It leads to the formation of a large, amount of ketone bodies. It is called ketogenic effect of, glucocorticoids., Hypersecretion of glucocorticoids causes an, abnormal type of obesity by increasing the deposition, of fat in certain areas such as abdomen, chest, face and, buttocks., , Glucocorticoids play an important role in the maintenance, of water balance, by accelerating excretion of water. The, adrenal insufficiency causes water retention and water, intoxication after intake of large quantity of water., 5. On Mineral Metabolism, Glucocorticoids enhance the retention of sodium and, to lesser extent, increase the excretion of potassium., Thus, hypersecretion of glucocorticoids causes edema,, hypertension, hypokalemia and muscular weakness., Glucocorticoids decrease the blood calcium by inhibiting, its absorption from intestine and increasing the excretion, through urine., 6. On Bone, stimulate, , 10. On Central Nervous System, Glucocorticoids are essential for normal functioning, of nervous system. Insufficiency of these hormones, causes personality changes like irritability and lack of, concentration. Sensitivity to olfactory and taste stimuli, increases in adrenal insufficiency., 11. Permissive Action of Glucocorticoids, , 4. On Water Metabolism, , Glucocorticoids, , to adrenaline and noradrenaline, leading to vascular, collapse., , the, , bone, , resorption, , (osteoclastic activity) and inhibit bone formation and, mineralization (osteoblastic activity). So, in hypersecretion of glucocorticoids, osteoporosis occurs., , 7. On Muscles, Glucocorticoids increase the catabolism of proteins in, muscle. So, hypersecretion causes muscular weakness, due to loss of protein., 8. On Blood Cells, Glucocorticoids decrease the number of circulating, eosinophils by increasing the destruction of eosinophils, in reticuloendothelial cells. These hormones also, decrease the number of basophils and lymphocytes and, increase the number of circulating neutrophils, RBCs, and platelets., 9. On Vascular Response, Presence of glucocorticoids is essential for the, constrictor action of adrenaline and noradrenaline. In, adrenal insufficiency, the blood vessels fail to respond, , Permissive action of glucocorticoids refers to execution, of actions of some hormones only in the presence of, glucocorticoids., Examples:, i. Calorigenic effect of glucagon, ii. Lipolytic effect of catecholamines, iii. Vascular effects of catecholamines, iv. Bronchodilator effect of catecholamines., 12. On Resistance to Stress, Exposure to any type of stress, either physical or, mental, increases the secretion of adrenocorticotropic, hormone (ACTH), which in turn increases glucocorticoid, secretion. The increase in glucocorticoid level is very, essential for survival during stress conditions, as it offers, high resistance to the body against stress., Glucocorticoids enhance the resistance by the, following ways:, i. Immediate release and transport of amino acids, from tissues to liver cells for the synthesis of, new proteins and other substances, which are, essential to withstand the stress, ii. Release of fatty acids from cells for the production, of more energy during stress, iii. Enhancement of vascular response to, catecholamines and fatty acid-mobilizing, action of catecholamines, which are necessary, to withstand the stress, iv. Prevention of severity of other changes in the, body caused by stress., 13. Anti-inflammatory Effects, Inflammation is defined as a localized protective, response induced by injury or destruction of tissues., When the tissue is injured by mechanical or chemical, factors, some substances are released from the affected, area. These substances produce series of reactions in, the affected area:
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432 Section 6 t Endocrinology, i. Chemical substances such as histamine,, serotonin, leukotrienes, prostaglandins and, bradykinin, which are released from damaged, tissue cause vasodilatation and erythema, (rushing of blood) in the affected area, ii. From blood, many leukocytes, particularly, neutrophils and monocytes infiltrate the affected, area. Leukocytes play an important role in the, defensive mechanism (Chapter 16), iii. Vasodilator substances released in the affected, area increase the permeability of capillary, membrane, resulting in oozing out of fluid from, blood into interstitial space, iv. Coagulation occurs in the interstitial fluid, because of fibrinogen and other proteins, which, are leaked out from blood, v. Finally, edema occurs in that area which may be, non-pitting type because of hard clot formation., Glucocorticoids, prevent, the, inflammatory, reactions. Even if inflammation has already started, the, glucocorticoids cause an early resolution of inflammation, and rapid healing., Glucocorticoids prevent the inflammatory changes, by:, i. Inhibiting the release of chemical substances, from damaged tissues and thereby preventing, vasodilatation and erythema in the affected, area, ii. Causing vasoconstriction through the permissive, action on catecholamines. This also prevents, rushing of blood to the injured area, iii. Decreasing the permeability of capillaries and, preventing loss of fluid from plasma into the, affected tissue, iv. Inhibiting the migration of leukocytes into the, affected area, v. Suppressing T cells and other leukocytes, so, that there is reduction in the reactions of tissues, which enhance the inflammatory process., 14. Anti-allergic Actions, Corticosteroids prevent various reactions in allergic, conditions as in the case of inflammation., 15. Immunosuppressive Effects, Glucocorticoids suppress the immune system of, the body by decreasing the number of circulating T, lymphocytes. It is done by suppressing proliferation, of T cells and the lymphoid tissues (lymph nodes and, thymus). Glucocorticoids also prevent the release of, interleukin-2 by T cells., , Thus, hypersecretion or excess use of glucocorticoids, decreases the immune reactions against all foreign, bodies entering the body. It leads to severe infection, causing death., Immunological reactions, which are common, during organ transplantation, may cause rejection of, the transplanted tissues. Glucocorticoids are used to, suppress the immunological reactions because of their, immunosuppressive action., MODE OF ACTION, Glucocorticoids bind with receptors to form hormonereceptor complex, which activates DNA to form mRNA., mRNA causes synthesis of enzymes, which alter the, cell function., REGULATION OF SECRETION, Anterior pituitary regulates glucocorticoid secretion, by secreting adrenocorticotropic hormone (ACTH)., ACTH secretion is regulated by hypothalamus through, corticotropin-releasing factor (CRF)., Role of Anterior Pituitary – ACTH, Anterior pituitary controls the activities of adrenal cortex, by secreting ACTH. ACTH is mainly concerned with the, regulation of cortisol secretion and it plays only a minor, role in the regulation of mineralocorticoid secretion., Source of secretion, ACTH is secreted by the basophilic chromophilic cells of, anterior pituitary., Chemistry, plasma level and half-life, ACTH is a single chained polypeptide with 39 amino, acids. The daily output of this hormone is 10 ng and the, concentration in plasma is 3 ng/dL. Half-life of ACTH is, 10 minutes., Synthesis, ACTH is synthesized from a protein called preproopiomelanocortin (POMC). Along with ACTH, the POMC, gives rise to some more byproducts called β-lipotropin,, γ-lipotropin and β-endorphin. Two more byproducts,, namely α-melanocyte-stimulating hormone (α-MSH), and β-melanocyte-stimulating hormone (β-MSH) are, also secreted in animals. However, MSH activity is, shown by ACTH and other byproducts from POMC in, human beings., Actions, ACTH is necessary for the structural integrity and, secretory activity of adrenal cortex. It has other functions, also.
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Chapter 70 t Adrenal Cortex 433, Actions of ACTH on adrenal cortex (Adrenal actions), 1. Maintenance of structural integrity and vascularization of zona fasciculata and zona reticularis of, adrenal cortex. In hypophysectomy, these two, layers in the adrenal cortex are atrophied, 2. Conversion of cholesterol into pregnenolone,, which is the precursor of glucocorticoids. Thus,, adrenocorticotropic hormone is responsible for the, synthesis of glucocorticoids, 3. Release of glucocorticoids, 4. Prolongation of glucocorticoid action on various, cells., Other (Nonadrenal) actions of ACTH, 1. Mobilization of fats from tissues, 2. Melanocyte-stimulating effect. Because of structural, similarity with melanocyte-stimulating hormone, (MSH), ACTH shows melanocyte-stimulating effect., It causes darkening of skin by acting on melanophores, which are the cutaneous pigment cells, containing melanin., Mode of action of ACTH, ACTH acts by the formation of cyclic AMP., Role of Hypothalamus, Hypothalamus also plays an important role in the, regulation of cortisol secretion by controlling the ACTH, secretion through corticotropin-releasing factor (CRF)., It is also called corticotropin-releasing hormone. CRF, reaches the anterior pituitary through the hypothalamohypophyseal portal vessels., CRF stimulates the corticotropes of anterior pituitary, and causes the synthesis and release of ACTH., CRF secretion is induced by several factors such, as emotion, stress, trauma and circadian rhythm., CRF in turn, causes release of ACTH, which induces, glucocorticoid secretion., Feedback Control, Cortisol regulates its own secretion through negative, feedback control by inhibiting the release of CRF from, hypothalamus and ACTH from anterior pituitary (Fig., 70.7)., Circadian rhythm of ACTH, ACTH secretion follows circadian rhythm (Chapter, 149), i.e. it varies in different periods of the day. The, rate of secretion of both ACTH and CRF is high in the, morning and low in the evening. Hypothalamus plays, an important role in the circadian fluctuations of ACTH, secretion., , FIGURE 70.7: Regulation of cortisol secretion, , ADRENAL SEX HORMONES, Adrenal sex hormones are secreted mainly by zona, reticularis. Zona fasciculata secretes small quantities, of sex hormones. Adrenal cortex secretes mainly the, male sex hormones, which are called androgens. But, small quantity of estrogen and progesterone are also, secreted by adrenal cortex. Synthesis of sex hormones, is given in Fig. 70.8., Androgens secreted by adrenal cortex:, 1. Dehydroepiandrosterone, 2. Androstenedione, 3. Testosterone., Dehydroepiandrosterone is the most active adrenal, androgen. Androgens, in general, are responsible, for masculine features of the body (Chapter 74). But, in normal conditions, the adrenal androgens have, insignificant physiological effects, because of the low, amount of secretion both in males and females., In congenital hyperplasia of adrenal cortex or tumor, of zona reticularis, an excess quantity of androgens is, secreted. In males, it does not produce any special effect, because, large quantity of androgens are produced by, testes also. But in females, the androgens produce, masculine features. Some of the androgens are, converted into testosterone. Testosterone is responsible
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434 Section 6 t Endocrinology, , FIGURE 70.8: Synthesis of adrenal sex hormones, , for the androgenic activity in adrenogenital syndrome, or congenital adrenal hyperplasia., , EXOGENOUS STEROIDS, Corticosteroids are used as drugs since long. Exogenous steroids are extracted from adrenal cortex of animals, or prepared artificially., Commercially available synthetic drugs with corticosteroid effects are widely used. These drugs are either, used as replacement of natural hormones (replacement, therapy) in patients with deficiency disorders such as, Addison disease or to treat a variety of other conditions such as arthritis, allergic conditions, asthma, skin, disorders, etc., SYNTHETIC STEROIDS, Synthetic steroids that are commonly used are:, 1. Cortisone and hydrocortisone, which are used for, replacement therapy have both glucocorticoid and, mineralocorticoid effects, 2. Prednisolone has more glucocorticoid activity than, mineralocorticoid activity, 3. Fludrocortisone (9-fluorocortisol) has more, mineralocorticoid activity than glucocorticoid activity., It has most potent mineralocorticoid effect., 4. Dexamethasone has only glucocorticoid effect., , APPLIED PHYSIOLOGY, HYPERACTIVITY OF ADRENAL CORTEX, Hypersecretion of adrenocortical hormones leads to the, following conditions:, 1. Cushing syndrome, 2. Hyperaldosteronism, 3. Adrenogenital syndrome., CUSHING SYNDROME, Cushing syndrome is a disorder characterized by, obesity., Causes, Cushing syndrome is due to the hypersecretion of, glucocorticoids, particularly cortisol. It may be either, due to pituitary origin or adrenal origin., If it is due to pituitary origin, it is known as Cushing, disease. If it is due to adrenal origin it is called Cushing, syndrome. Generally, these two terms are used, interchangeably., Pituitary Origin, Increased secretion of ACTH causes hyperplasia of, adrenal cortex, leading to hypersecretion of glucocorticoid. ACTH secretion is increased by:, i. Tumor in pituitary cells, particularly in basophilic, cells which secrete ACTH
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Chapter 70 t Adrenal Cortex 435, ii. Malignant tumor of non-endocrine origin like, cancer of lungs or abdominal viscera, iii. Hypothalamic disorder causing hypersecretion, of corticotropin-releasing hormone., Adrenal Origin, Cortisol secretion is increased by:, i. Tumor in zona fasciculata of adrenal cortex, ii. Carcinoma of adrenal cortex, iii. Prolonged treatment of chronic inflammatory, diseases like rheumatoid arthritis, with high, dose of exogenous glucocorticoids, iv. Prolonged treatment with high dose of ACTH,, which stimulates adrenal cortex to secrete, excess glucocorticoids., Recently, Cushing syndrome is classified into two, types:, i. ACTH-dependent Cushing syndrome which is, due to hypersecretion of ACTH, ii. ACTH-independent Cushing syndrome in, which the secretion of ACTH is normal. The, syndrome develops due to abnormal membrane, receptors for some peptides like interleukin-1,, gonadotropin-releasing hormone and gastric, inhibitory polypeptide in the cells of zona, fasciculata. The binding of these peptides to, the abnormal receptors increases secretion of, glucocorticoids, resulting in Cushing syndrome., Cushing syndrome that is developed by, treatment with exogenous glucocorticoids also, belongs to this type., Signs and Symptoms, i. Characteristic feature of this disease is the, disproportionate distribution of body fat, resulting in some abnormal features:, a. Moon face: The edematous facial appearance, due to fat accumulation and retention of, water and salt, b. Torso: Fat accumulation in the chest and, abdomen. Arms and legs are very slim in, proportion to torso (torso means trunk of the, body), c. Buffalo hump: Due to fat deposit on the back, of neck and shoulder, d. Pot belly: Due to fat accumulation in upper, abdomen (Fig. 70.9)., ii. Purple striae: Reddish purple stripes on, abdomen due to three reasons:, a. Stretching of abdominal wall by excess, subcutaneous fat, , FIGURE 70.9: Cushing syndrome, (Courtesy: Prof Mafauzy Mohamad), , iii., iv., , v., , vi., , vii., viii., ix., x., , xi., , xii., , xiii., xiv., , b. Rupture of subdermal tissues due to stretching, c. Deficiency of collagen fibers due to protein, depletion., Thinning of extremities, Thinning of skin and subcutaneous tissues, due to protein depletion caused by increased, catabolism of proteins, Aconthosis: Skin disease characterized by, darkened skin patches in certain areas such as, axilla, neck and groin, Pigmentation of skin, especially in ACTHdependent type due to hypersecretion of ACTH, which has got melanocyte-stimulating effect, Facial plethora: Facial redness, Hirsutism: Heavy growth of body and facial hair, Weakening of muscles because of protein, depletion, Bone resorption and osteoporosis due to protein, depletion. Bone becomes susceptible to easy, fracture, Hyperglycemia due to gluconeogenesis (from, proteins) and inhibition of peripheral utilization, of glucose. Hyperglycemia leads to glucosuria, and adrenal diabetes, Hypertension by the mineralocorticoid effects of, glucocorticoids – retention of sodium and water, results in increase in ECF volume and blood, volume, leading to hypertension, Immunosuppression resulting in susceptibility, for infection, Poor wound healing., , Tests for Cushing Syndrome, i. Observation of external features, ii. Determination of blood sugar and cortisol levels, iii. Analysis of urine for 17-hydroxysteroids.
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436 Section 6 t Endocrinology, Treatment for Cushing Syndrome, Treatment depends upon the cause of the disease., Treatment may include cortisol-inhibiting drugs, surgical, removal of pituitary or adrenal tumor, radiation or, chemotherapy., , iv. Muscular weakness due to potassium depletion, v. Metabolic alkalosis due to secretion of large, amount of hydrogen ions into the renal tubules., Metabolic alkalosis reduces blood calcium level, causing tetany., , Nelson syndrome, , ADRENOGENITAL SYNDROME, , Nelson syndrome is a disorder that develops after, surgical removal of both adrenal glands. It is because of, the growth of pituitary tumor that secretes excess ACTH., The features include headache and visual problems., Nelson syndrome can be treated with radiation or, surgical removal of the pituitary gland., , Under normal conditions, adrenal cortex secretes small, quantities of androgens which do not have any significant, effect on sex organs or sexual function. However, secretion, of abnormal quantities of adrenal androgens develops, adrenogenital syndrome. Testosterone is responsible for, the androgenic activity in adrenogenital syndrome., , HYPERALDOSTERONISM, , Causes, , Increased secretion, hyperaldosteronism., , of, , aldosterone, , is, , called, , Adrenogenital syndrome is due to the tumor of zona, reticularis in adrenal cortex., , Causes and Types, , Symptoms, , Depending upon the causes, hyperaldosteronism is, classified into two types:, i. Primary hyperaldosteronism, ii. Secondary hyperaldosteronism., , Adrenogenital syndrome is characterized by the, tendency for the development of secondary sexual, character of opposite sex., , Primary Hyperaldosteronism, , Increased secretion of androgens causes development, of male secondary sexual characters. The condition is, called adrenal virilism. Symptoms are:, i. Masculinization due to increased muscular, growth, ii. Deepening of voice, iii. Amenorrhea, iv. Enlargement of clitoris, v. Male type of hair growth., , Primary hyperaldosteronism is otherwise known as, Conn syndrome. It develops due to tumor in zona, glomerulosa of adrenal cortex. In primary hyperaldosteronism, edema does not occur because of, escape phenomenon., Secondary Hyperaldosteronism, Secondary hyperaldosteronism occurs due to extra, adrenal causes such as:, i. Congestive cardiac failure, ii. Nephrosis, iii. Toxemia of pregnancy, iv. Cirrhosis of liver., Signs and Symptoms, i. Increase in ECF volume and blood volume, ii. Hypertension due to increase in ECF volume, and blood volume, iii. Severe depletion of potassium, which causes, renal damage. The kidneys fail to produce, concentrated urine. It leads to polyuria and, polydipsia, , Symptoms in females, , Symptoms in males, Sometimes, the tumor of estrogen secreting cells, produces more than normal quantity of estrogens in, males. It produces some symptoms such as:, i. Feminization, ii. Gynecomastia (enlargement of breast), iii. Atrophy of testis, iv. Loss of interest in women., HYPOACTIVITY OF ADRENAL CORTEX, Hyposecretion of adrenocortical hormones leads to the, following conditions:, 1. Addison disease or chronic adrenal insufficiency, 2. Congenital adrenal hyperplasia.
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Chapter 70 t Adrenal Cortex 437, ADDISON DISEASE OR CHRONIC, ADRENAL INSUFFICIENCY, Addison disease is the failure of adrenal cortex to secrete, corticosteroids., Types of Addison Disease, i. Primary Addison disease due to adrenal cause, ii. Secondary Addison disease due to failure of, anterior pituitary to secrete ACTH, iii. Tertiary Addison disease due failure of hypothalamus to secrete corticotropin-releasing factor, (CRF)., Causes for Primary Addison Disease, i. Atrophy of adrenal cortex due to autoimmune, diseases, ii. Destruction of the gland because of, tuberculosis, iii. Destruction of hormone-secreting cells in, adrenal cortex by malignant tissues, iv. Congenital failure to secrete cortisol, v. Adrenalectomy and failure to take hormone, therapy., , ii. Measurement of amount of steroids excreted in, urine., Addisonian Crisis or Adrenal Crisis, or Acute Adrenal Insufficiency, Adrenal crisis is a common symptom of Addison disease,, characterized by sudden collapse associated with an, increase in need for large quantities of glucocorticoids., The condition becomes fatal if not treated in time., Causes, i., ii., iii., iv., v., , Exposure to even mild stress, Hypoglycemia due to fasting, Trauma, Surgical operation, Sudden withdrawal of glucocorticoid treatment., , CONGENITAL ADRENAL HYPERPLASIA, Congenital adrenal hyperplasia is a congenital, disorder, characterized by increase in size of adrenal, cortex. Size increases due to abnormal increase in the, number of steroid-secreting cortical cells., , Signs and Symptoms, , Causes, , Signs and symptoms develop in Addison disease, because of deficiency of both cortisol and aldosterone., Common signs and symptom are:, i. Pigmentation of skin and mucous membrane, due to excess ACTH secretion, induced by, cortisol deficiency. ACTH causes pigmentation, by its melanocyte-stimulating action, ii. Muscular weakness, iii. Dehydration with loss of sodium, iv. Hypotension, v. Decreased cardiac output and decreased, workload of the heart, leading to decrease in, size of the heart, vi. Hypoglycemia, vii. Nausea, vomiting and diarrhea. Prolonged, vomiting and diarrhea cause dehydration and, loss of body weight, viii. Susceptibility to any type of infection, ix. Inability to withstand any stress, resulting in, Addisonian crisis (see below)., , Even though the size of the gland increases, cortisol, secretion decreases. It is because of the congenital, deficiency of the enzymes necessary for the synthesis, of cortisol, particularly, 21-hydroxylase., Lack of this enzyme reduces the synthesis of, cortisol, resulting in ACTH secretion from pituitary by, feedback mechanism. ACTH stimulates the adrenal, cortex causing hyperplasia, with accumulation of lipid, droplets. Hence, it is also called congenital lipid adrenal, , Tests for Addison Disease, i. Measurement of blood level of cortisol and, aldosterone, , FIGURE 70.10: Congenital adrenal hyperplasia (Macrogenitosomia praecox) (Courtesy: Prof Mafauzy Mohamad)
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438 Section 6 t Endocrinology, hyperplasia. Cortisol cannot be synthesized because of, , lack of 21-hydroxylase. Therefore, due to the constant, simulation of adrenal cortex by ACTH, the secretion of, androgens increases. It results in sexual abnormalities, such as virilism., , Features of macrogenitosomia praecox:, i. Precocious body growth, causing stocky appearance called infant Hercules, ii. Precocious sexual development with enlarged, penis even at the age of 4 years., In girls, , Symptoms, , Adrenal hyperplasia produces a condition known as, , In girls, adrenal hyperplasia produces masculinization., It is otherwise called virilism. In some cases of genetic disorders, the female child is born with external, genitalia of male type. This condition is called, , macrogenitosomia praecox (Fig. 70.10)., , pseudohermaphroditism., , In boys
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Chapter, , Adrenal Medulla, , 71, , INTRODUCTION, HORMONES OF ADRENAL MEDULLA, , , , PLASMA LEVEL OF CATECHOLAMINES, HALF-LIFE OF CATECHOLAMINES, , SYNTHESIS OF CATECHOLAMINES, METABOLISM OF CATECHOLAMINES, ACTIONS OF ADRENALINE AND NORADRENALINE, , , , MODE OF ACTION – ADRENERGIC RECEPTORS, ACTIONS, , REGULATION OF SECRETION OF ADRENALINE AND NORADRENALINE, DOPAMINE, APPLIED PHYSIOLOGY – PHEOCHROMOCYTOMA, , INTRODUCTION, Medulla is the inner part of adrenal gland and it forms, 20% of the mass of adrenal gland. It is made up of, interlacing cords of cells known as chromaffin cells., Chromaffin cells are also called pheochrome cells or, chromophil cells. These cells contain fine granules, which are stained brown by potassium dichromate., Types of chromaffin cells, Adrenal medulla is formed by two types of chromaffin, cells:, 1. Adrenaline-secreting cells (90%), 2. Noradrenaline-secreting cells (10%)., , PLASMA LEVEL OF CATECHOLAMINES, 1. Adrenaline, : 3 µg/dL, 2. Noradrenaline : 30 µg/dL, 3. Dopamine, : 3.5 µg/dL, HALF-LIFE OF CATECHOLAMINES, Half-life of catecholamines is about 2 minutes., , SYNTHESIS OF CATECHOLAMINES, Catecholamines are synthesized from the amino acid, tyrosine in the chromaffin cells of adrenal medulla (Fig., 71.1). These hormones are formed from phenylalanine, also. But phenylalanine has to be converted into tyrosine., , HORMONES OF ADRENAL MEDULLA, Adrenal medullary hormones are the amines derived, from catechol and so these hormones are called, catecholamines., , Catecholamines secreted by adrenal medulla, 1. Adrenaline or epinephrine, 2. Noradrenaline or norepinephrine, 3. Dopamine., , Stages of Synthesis of Catecholamines, 1. Formation of tyrosine from phenylalanine in the, presence of enzyme phenylalanine hydroxylase, 2. Uptake of tyrosine from blood into the chromaffin, cells of adrenal medulla by active transport, 3. Conversion of tyrosine into dihydroxyphenylalanine, (DOPA) by hydroxylation in the presence of tyrosine, hydroxylase
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440 Section 6 t Endocrinology, , FIGURE 71.2: Metabolism of catecholamines. COMT =, Catechol-O-methyltransferase, MAO = Monoamine oxidase., , Stages of Metabolism of Catecholamines, 1. Methoxylation of adrenaline into meta-adrenaline, and noradrenaline into metanoradrenaline in, the presence of ‘catechol-O-methyltransferase’, (COMT). Meta-adrenaline and meta-noradrenaline, are together called metanephrines, 2. Oxidation of metanephrines into vanillylmandelic, acid (VMA) by monoamine oxidase (MAO), Removal of Catecholamines, FIGURE 71.1: Synthesis of catecholamines. DOPA = Dihydroxyphenylalanine, PNMT = Phenylethanolamine-Nmethyltransferase., , 4. Decarboxylation of DOPA into dopamine by DOPA, decarboxylase, , 5. Entry of dopamine into granules of chromaffin cells, 6. Hydroxylation of dopamine into noradrenaline by, the enzyme dopamine beta-hydroxylase, 7. Release of noradrenaline from granules into the, cytoplasm, 8. Methylation of noradrenaline into adrenaline by the, most important enzyme called phenylethanolamineN-methyltransferase (PNMT). PNMT is present in, chromaffin cells., , Catecholamines are removed from body through urine, in three forms:, i. 15% as free adrenaline and free noradrenaline, ii. 50% as free or conjugated meta-adrenaline and, meta-noradrenaline, iii. 35% as vanillylmandelic acid (VMA)., , ACTIONS OF ADRENALINE, AND NORADRENALINE, Adrenaline and noradrenaline stimulate the nervous, system. Adrenaline has significant effects on metabolic, functions and both adrenaline and noradrenaline have, significant effects on cardiovascular system., , METABOLISM OF CATECHOLAMINES, , MODE OF ACTION OF ADRENALINE, AND NORADRENALINE –, ADRENERGIC RECEPTORS, , Eighty five percent of noradrenaline is taken up by the, sympathetic adrenergic neurons. Remaining 15% of, noradrenaline and adrenaline are degraded (Fig. 71.2)., , Actions of adrenaline and noradrenaline are executed, by binding with receptors called adrenergic receptors,, which are present in the target organs.
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Chapter 71 t Adrenal Medulla 441, Adrenergic receptors are of two types:, 1. Alpha-adrenergic receptors, which are subdivided, into alpha-1 and alpha-2 receptors, 2. Beta-adrenergic receptors, which are subdivided, into beta-1 and beta-2 receptors., Refer Table 71.1 for the mode of action of these, receptors., ACTIONS, Circulating adrenaline and noradrenaline have similar, effect of sympathetic stimulation. But, the effect of, adrenal hormones is prolonged 10 times more than, that of sympathetic stimulation. It is because of the, slow inactivation, slow degradation and slow removal of, these hormones., Effects of adrenaline and noradrenaline on various, target organs depend upon the type of receptors present, in the cells of the organs. Adrenaline acts through, both alpha and beta receptors equally. Noradrenaline, acts mainly through alpha receptors and occasionally, through beta receptors., 1. On Metabolism (via Alpha and Beta Receptors), Adrenaline influences the metabolic functions more than, noradrenaline., i. General metabolism: Adrenaline increases, oxygen consumption and carbon dioxide, removal. It increases basal metabolic rate. So, it, is said to be a calorigenic hormone, ii. Carbohydrate metabolism: Adrenaline increases, the blood glucose level by increasing the, glycogenolysis in liver and muscle. So, a large, quantity of glucose enters the circulation, iii. Fat metabolism: Adrenaline causes mobilization, of free fatty acids from adipose tissues., Catecholamines need the presence of, glucocorticoids for this action., 2. On Blood (via Beta Receptors), Adrenaline decreases blood coagulation time. It, increases RBC count in blood by contracting smooth, , muscles of splenic capsule and releasing RBCs from, spleen into circulation., 3. On Heart (via Beta Receptors), Adrenaline has stronger effects on heart than noradrenaline. It increases overall activity of the heart, i.e., i. Heart rate (chronotropic effect), ii. Force of contraction (inotropic effect), iii. Excitability of heart muscle (bathmotropic, effect), , iv. Conductivity in heart muscle (dromotropic, effect)., , 4. On Blood Vessels (via Alpha and, Beta-2 Receptors), Noradrenaline has strong effects on blood vessels., It causes constriction of blood vessels throughout, the body via alpha receptors. So it is called ‘general, vasoconstrictor’. Vasoconstrictor effect of noradrenaline increases total peripheral resistance., Adrenaline also causes constriction of blood vessels., However, it causes dilatation of blood vessels in skeletal, muscle, liver and heart through beta-2 receptors. So, the, total peripheral resistance is decreased by adrenaline., Catecholamines need the presence of glucocorticoids, for these vascular effects., 5. On Blood Pressure (via Alpha and, Beta Receptors), Adrenaline increases systolic blood pressure by, increasing the force of contraction of the heart and, cardiac output. But, it decreases diastolic blood, pressure by reducing the total peripheral resistance., Noradrenaline increases diastolic pressure due to, general vasoconstrictor effect by increasing the total, peripheral resistance. It also increases the systolic, blood pressure to a slight extent by its actions on heart., The action of catecholamines on blood pressure needs, the presence of glucocorticoids., , TABLE 71.1: Adrenergic receptors, Receptor, , Mode of action, , Response, , Alpha-1 receptor, , Activates IP3 through phospholipase C, , Alpha-2 receptor, , Inhibits adenyl cyclase and cAMP, , Beta-1 receptor, , Activates adenyl cyclase and cAMP, , Mediates actions of adrenaline and noradrenaline, equally, , Beta-2 receptor, , Activates adenyl cyclase and cAMP, , Mediates more of adrenaline actions than, noradrenaline actions, , IP3 = Inositol triphosphate, , Mediates more of noradrenaline actions than, adrenaline actions
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442 Section 6 t Endocrinology, Thus, hypersecretion of catecholamines leads to, hypertension., 6. On Respiration (via Beta-2 Receptors), Adrenaline increases rate and force of respiration., Adrenaline injection produces apnea, which is known, as adrenaline apnea. It also causes bronchodilation., 7. On Skin (via Alpha and Beta-2 Receptors), Adrenaline causes contraction of arrector pili. It also, increases the secretion of sweat., 8. On Skeletal Muscle (via Alpha and, Beta-2 Receptors), Adrenaline causes severe contraction and quick fatigue, of skeletal muscle. It increases glycogenolysis and, release of glucose from muscle into blood. It also causes, vasodilatation in skeletal muscles., 9. On Smooth Muscle (via Alpha and, Beta Receptors), Catecholamines cause contraction of smooth muscles, in the following organs:, i. Splenic capsule, ii. Sphincters of gastrointestinal (GI) tract, iii. Arrector pili of skin, iv. Gallbladder, v. Uterus, vi. Dilator pupillae of iris, vii. Nictitating membrane of cat., Catecholamines cause relaxation of smooth, muscles in the following organs:, i. Non-sphincteric part of GI tract (esophagus,, stomach and intestine), ii. Bronchioles, iii. Urinary bladder., 10. On Central Nervous System, (via Beta Receptors), , ii. On sweat glands (via beta-2 receptors): Increase, the secretion of apocrine sweat glands, iii. On lacrimal glands (via alpha receptors):, Increase the secretion of tears, iv. On ACTH secretion (via alpha receptors):, Adrenaline increases ACTH secretion, v. On nerve fibers (via alpha receptors): Adrenaline, decreases the latency of action potential, in the nerve fibers, i.e. electrical activity is, accelerated, vi. On renin secretion (via beta receptors): Increase, the rennin secretion from juxtaglomerular, apparatus of the kidney., , REGULATION OF SECRETION, OF ADRENALINE AND NORADRENALINE, Adrenaline and noradrenaline are secreted from adrenal, medulla in small quantities even during rest. During, stress conditions, due to sympathoadrenal discharge,, a large quantity of catecholamines is secreted. These, hormones prepare the body for fight or flight reactions., Catecholamine secretion increases during exposure, to cold and hypoglycemia also., , DOPAMINE, Dopamine is secreted by adrenal medulla. Type of cells, secreting this hormone is not known. Dopamine is also, secreted by dopaminergic neurons in some areas of, brain, particularly basal ganglia. In brain, this hormone, acts as a neurotransmitter., Injected dopamine produces the following effects:, 1. Vasoconstriction by releasing norepinephrine, 2. Vasodilatation in mesentery, 3. Increase in heart rate via beta receptors, 4. Increase in systolic blood pressure. Dopamine does, not affect diastolic blood pressure., Deficiency of dopamine in basal ganglia produces, nervous disorder called parkinsonism (Chapter 151)., , APPLIED PHYSIOLOGY –, PHEOCHROMOCYTOMA, , Adrenaline increases the activity of brain. Adrenaline, secretion increases during ‘fight or flight reactions’ after, exposure to stress. It enhances the cortical arousal and, other facilitatory functions of central nervous system., , Pheochromocytoma is a condition characterized by, hypersecretion of catecholamines., , 11. Other Effects of Catecholamines, , Cause, , i. On salivary glands (via alpha and beta-2, receptors): Cause vasoconstriction in salivary, gland, leading to mild increase in salivary, secretion, , Pheochromocytoma is caused by tumor of chromophil, cells in adrenal medulla. It is also caused rarely, by tumor of sympathetic ganglia (extra-adrenal, pheochromocytoma).
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Chapter 71 t Adrenal Medulla 443, Signs and Symptoms, Characteristic feature of pheochromocytoma is hypertension. This type of hypertension is known as endocrine, or secondary hypertension., 1., 2., 3., 4., 5., 6., , Other features:, Anxiety, Chest pain, Fever, Headache, Hyperglycemia, Metabolic disorders, , 7., 8., 9., 10., 11., 12., , Nausea and vomiting, Palpitation, Polyuria and glucosuria, Sweating and flushing, Tachycardia, Weight loss., , Tests for Pheochromocytoma, Pheochromocytoma is detected by measuring metanephrines and vanillylmandelic acid in urine and, catecholamines in plasma.
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Endocrine Functions, of Other Organs, , Chapter, , 72, , PINEAL GLAND, , , , SITUATION AND STRUCTURE, FUNCTIONS, , THYMUS, , , , SITUATION, FUNCTIONS, , KIDNEYS, , , , , , , ERYTHROPOIETIN, THROMBOPOIETIN, RENIN, 1,25-DIHYDROXYCHOLECALCIFEROL, PROSTAGLANDINS, , HEART, , , , , ATRIAL NATRIURETIC PEPTIDE, BRAIN NATRIURETIC PEPTIDE, C-TYPE NATRIURETIC PEPTIDE, , PINEAL GLAND, , Melatonin, , SITUATION AND STRUCTURE, , Source of secretion, , Pineal gland or epiphysis is located in the diencephalic, area of brain above the hypothalamus. It is a small coneshaped structure with a length of about 10 mm., Pineal gland has two types of cells:, 1. Large epithelial cells called parenchymal cells, 2. Neuroglial cells., In adults, the pineal gland is calcified. But, the epithelial, cells exist and secrete the hormonal substance., , Melatonin is secreted by the parenchymal cells of pineal, gland., , FUNCTIONS, Pineal gland has two functions:, 1. It controls the sexual activities in animals by, regulating the seasonal fertility. However, the, pineal gland plays little role in regulating the sexual, functions in human being, 2. It secretes the hormonal substance called, melatonin., , Chemistry, Melatonin is an indole (N-acetyl-5-methoxytryptamine)., Actions of melatonin, Melatonin acts mainly on gonads. Its action differs from, species to species. In some animals, it stimulates the, gonads while in other animals, it inhibits the gonads., In humans, it inhibits the onset of puberty by, inhibiting the gonads., Diurnal variation in melatonin secretion, Melatonin secretion is more in darkness than in daylight., In animals, the secretion of melatonin varies according, to activities in different periods of the day, i.e. circadian
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Chapter 72 t Endocrine Functions of Other Organs 445, rhythm (Chapter 149). Hypothalamus is responsible for, the circadian fluctuations of melatonin secretion., , Recently, it is discovered that kidney secretes small, quantity of C-type natriuretic peptide (see below)., , THYMUS, , ERYTHROPOIETIN, , SITUATION, , Source of Secretion, , Thymus is situated in front of trachea, below the thyroid, gland. Thymus is small in newborn infants and gradually, enlarges till puberty and then decreases in size., , Endothelial cells of peritubular capillaries in the kidney, secrete erythropoietin. The stimulant for its secretion is, hypoxia. Erythropoietin is a glycoprotein with 165 amino, acids., , FUNCTIONS, Thymus has lymphoid function and endocrine function., It plays an important role in development of immunity in, the body., Thymus has two functions:, 1. Processing the T lymphocytes, 2. Endocrine function., 1. Processing the T Lymphocytes, Thymus plays an essential role in the development of, immunity by processing the T lymphocytes (Chapter 17)., The lymphocytes which are produced in bone marrow, are processed in thymus into T lymphocytes. It occurs, during the period between 3 months before birth and 3, months after birth. So, the removal of thymus 3 months, after birth, will not affect the cell-mediated immunity., 2. Endocrine Function of Thymus, Thymus secretes two hormones:, i. Thymosin, ii. Thymin., Thymosin, Thymosin is a peptide. It accelerates lymphopoiesis and, proliferation of T lymphocytes., Thymin, Thymin is also called thymopoietin. It suppresses, the neuromuscular activity by inhibiting acetylcholine, release. Hyperactivity of thymus causes myasthenia, gravis., , Action of Erythropoietin, Erythropoietin stimulates the bone marrow and causes, erythropoiesis. More details are given in Chapter 10., THROMBOPOIETIN, Source of Secretion, Thrombopoietin is a glycoprotein. It is secreted by, kidneys and liver., Action of Thrombopoietin, Thrombopoietin stimulates the production of platelets., RENIN, Source of Secretion, The granular cells of juxtaglomerular apparatus of the, kidney secrete renin., Actions of Renin, When renin is released into the blood, it acts on a specific, plasma protein called alpha-2 globulin. It is also called, angiotensinogen or renin substrate., Renin converts angiotensinogen into angiotensin I,, which is converted into angiotensin II by a converting, enzyme. The other details of renin and angiotensin II, are given in Chapter 50., 1,25-DIHYDROXYCHOLECALCIFEROL –, CALCITRIOL, , KIDNEYS, , Formation of 1,25-dihydroxycholecalciferol, , Kidneys secrete five hormonal substances:, 1. Erythropoietin, 2. Thrombopoietin, 3. Renin, 4. 1,25-dihydroxycholecalciferol (calcitriol), 5. Prostaglandins., , 1,25-dihydroxycholecalciferol is otherwise known, as calcitriol or activated vitamin D. It is formed from, cholecalciferol, which is present in skin and intestine., The cholecalciferol (vitamin D3) from skin or intestine is, converted into 25-hydroxycholecalciferol in liver. This in, turn, is activated into 1,25-dihydroxycholecalciferol by, parathormone in kidney (refer Chapter 68).
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446 Section 6 t Endocrinology, Actions of 1,25-Dihydroxycholecalciferol, The activated vitamin D plays an important role in, the maintenance of blood calcium level. It acts on, the intestinal epithelium and enhances absorption of, calcium from intestine into the blood. Details are given, in Chapter 68., PROSTAGLANDINS, Source of Secretion, Prostaglandins secreted from kidney are PGA2 and, PGE2. These hormones are secreted by juxtaglomerular, cells and type I interstitial cells present in medulla of, kidney., Action of Prostaglandins, Prostaglandins decrease the blood pressure by systemic vasodilatation, diuresis and natriuresis. Details of, prostaglandins are given in Chapter 73., , HEART, Heart secretes the hormones atrial natriuretic peptide, and brain natriuretic peptide. Recently, another peptide, called C-type natriuretic peptide is found in heart., ATRIAL NATRIURETIC PEPTIDE, Atrial natriuretic peptide (ANP) is a polypeptide with, 28 amino acids. It is secreted by atrial musculature of, the heart. Recently, it is found in hypothalamus of brain, also. However, its action in brain is not known., ANP is secreted during overstretching of atrial, muscles in conditions like increase in blood volume. ANP,, in turn increases excretion of sodium (followed by water, excretion) through urine and helps in the maintenance, of extracellular fluid (ECF) volume and blood volume. It, also lowers blood pressure., Effect of ANP on Sodium Excretion, Atrial natriuretic peptide increases excretion of sodium, ions through urine by:, 1. Increasing glomerular filtration rate by relaxing, mesangeal cells and dilating afferent arterioles, , 2. Inhibiting sodium reabsorption from distal convoluted tubules and collecting ducts in kidneys, 3. Increasing the secretion of sodium into the renal, tubules., Escape phenomenon, Thus, ANP is responsible for escape phenomenon and, prevention of edema in primary hyperaldosteronism, in, spite of increased ECF volume (Refer Chapter 70 for, details)., Effect of ANP on Blood Pressure, ANP decreases the blood pressure by:, 1. Vasodilatation by relaxing the smooth muscle fibers,, mainly in arterioles and venules, 2. Inhibiting renin secretion from juxtaglomerular, apparatus of kidney, 3. Inhibiting vasoconstrictor effect of angiotensin II, 4. Inhibiting vasoconstrictor effects of catecholamines., BRAIN NATRIURETIC PEPTIDE, Brain natriuretic peptide (BNP) is also called B-type, natriuretic peptide. It is a polypeptide with 32 amino, acids. It is secreted by the cardiac muscle. It is also, secreted in some parts of the brain. The stimulant for its, secretion is not known., BNP has same actions of ANP (see above). On, brain, its actions are not known., Clinical Importance of BNP, Measurement of plasma level of BNP (BNP test), is becoming an important diagnostic tool for heart, diseases. Normally, blood contains very small amount, of BNP. However, in conditions like heart failure, BNP, level is increased in blood., C-TYPE NATRIURETIC PEPTIDE, C-type natriuretic peptide (CNP) is the newly discovered, peptide hormone. It is a 22 amino acid peptide., Initially, it was identified in brain. Now, it is known to be, secreted by several tissues which include myocardium,, endothelium of blood vessels, gastrointestinal tract and, kidneys. The functions of this hormone are not fully, studied. It is believed that it has similar action of atrial, natriuretic peptide.
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Chapter, , Local Hormones, , 73, , INTRODUCTION, LOCAL HORMONES SYNTHESIZED IN TISSUES, , , , PROSTAGLANDINS AND ITS RELATED HORMONES, OTHER LOCAL HORMONES SYNTHESIZED IN TISSUES, , LOCAL HORMONES PRODUCED IN BLOOD, , , KININS, , INTRODUCTION, Local hormones are the substances which act on, the same area of their secretion or in immediate, neighborhood. The endocrine hormones are secreted, in one place but execute their actions on some other, remote place., Local hormones are usually released in an, inactive form and are activated by some conditions or, substances., , Classification of Local Hormones, Local hormones are classified into two types:, I. Hormones synthesized in tissues, II. Hormones synthesized in blood., , LOCAL HORMONES SYNTHESIZED, IN TISSUES, Local hormones synthesized in the tissues are:, 1. Prostaglandins and related substances, 2. Other local hormones synthesized in tissues., PROSTAGLANDINS AND, ITS RELATED HORMONES, Prostaglandins and other hormones which are, derived from arachidonic acid are collectively called, eicosanoids. The eicosanoids are:, 1. Prostaglandins, 2. Thromboxanes, 3. Prostacyclin, , 4. Leukotrienes, 5. Lipoxins, Synthesis of eicosanoids, Phospholipids of the cell membrane are released by the, action of phospholipase A2. Phospholipids are converted, into arachidonic acid. Arachidonic acid is converted into, an endoperoxide called prostaglandin G2 (PGG2), which, is converted into prostaglandin H2 (PGH2). PGH2 gives, rise to prostaglandins, prostacyclin and thromboxanes, (Fig. 73.1)., 1. Prostaglandins, Prostaglandins were first discovered and isolated from, human semen by Ulf von Euler of Sweden, in 1930. He, thought that these hormones were secreted by prostate, gland hence the name prostaglandins. However, now it is, believed that almost all the tissues of the body including, renal tissues (Chapter 72) synthesize prostaglandins., Chemistry, Prostaglandins are unsaturated fatty acids with a, cyclopentane ring and 20 carbon atoms., Synthesis, Prostaglandins are synthesized from arachidonic acid., Types, A variety of prostaglandins are identified. Active forms of, prostaglandins are PGA2, PGD2, PGE2 and PGF2.
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448 Section 6 t Endocrinology, , FIGURE 73.1: Synthesis of prostaglandins and related hormones., HPETE = Hydroperoxyeicosatetraenoic acid, , Actions, Prostaglandins show variety of physiological actions in, the body. Various actions of prostaglandins are:, i. On blood: Prostaglandins accelerate the capacity, of RBCs to pass through minute blood vessels., ii. On blood vessels: PGE2 causes vasodilatation., iii. On GI tract: The prostaglandins reduce gas, tric secretion. In experimental animals, prosta, glandins inhibit the formation of peptic ulcer., iv. On respiratory system: PGE2 causes, bronchodilatation., v. On lipids: Some of the prostaglandins are, antilipolytic agents. These hormones inhibit the, release of free fatty acids from adipose tissue., vi. On nervous system: In brain, prostaglandins, control or alter the actions of neurotransmitters., vii. On reproduction: Prostaglandins play an, important role in regulating the reproductive, cycle. These hormones also cause degeneration, of corpus luteum (luteolysis). Prostaglandins, increase the receptive capacity of cervical, mucosa for sperms and cause reverse peristaltic, movement of uterus and fallopian tubes during, coitus. This in turn, increases the velocity of, sperm transport in female genital tract., Prostaglandins (PGE2) play an important, role during parturition and facilitate labor by, increasing the force of uterine contractions., Prostaglandins are secreted from uterine, tissues, fetal membranes and placenta. Their, , concentration increases in maternal blood and, amniotic fluid at the time of labor. Prostaglandins, increase the force of uterine contractions by, elevating the concentration of calcium ions in, the smooth muscle fibers of uterus., When injected intra-amniotically during, pregnancy, prostaglandins induce abortion., When injected during last stages of pregnancy,, prostaglandins induce labor., viii. On kidney: The prostaglandins stimulate, juxtaglomerular apparatus and enhance the, secretion of renin, diuresis and natriuresis., Mode of action of prostaglandins, Prostaglandins mainly act by the formation of second, messenger cyclic AMP., 2. Thromboxanes, Thromboxanes are derived from arachidonic acid., Thromboxanes are of two types:, i. Thromboxane A2, which is secreted in platelets, ii. Thromboxane B2, the metabolite of thromboxane, A2., Actions, Thromboxane A2:, i. Causes vasoconstriction, ii. Plays an important role in hemostasis by acce, lerating aggregation of platelets, iii. Accelerates clot formation.
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Chapter 73 t Local Hormones 449, 3. Prostacyclin, , 1. Acetylcholine, , Prostacyclin is also a derivative of arachidonic acid. It, is produced in the endothelial cells and smooth muscle, cells of blood vessels., , Acetylcholine is the cholinergic neurotransmitter, (Chapter 164). It is the transmitter substance at neuro, muscular junction. It is also secreted by other nerve, endings and other cells., , Actions, It causes vasodilatation, aggregation., , and, , inhibits, , platelet, , 4. Leukotrienes, Leukotrienes are derived from arachidonic acid via, 5hydroperoxyeicosatetraeonic acid (5HPETE). Leuko, trienes are the mediators of allergic responses. These, hormones also promote inflammatory reactions., The release of leukotrienes increases when some, allergic agents combine with antibodies like IgE., Actions, Leukotrienes cause:, i. Bronchiolar constriction, ii. Arteriolar constriction, iii. Vascular permeability, iv. Attraction of neutrophils and eosinophils towards, the site of inflammation., 5. Lipoxins, Lipoxins are also derived from arachidonic acid via 15, hydroperoxyeicosatetraeonic acid (15HPETE). Lipoxins, are of two types namely, lipoxin A and lipoxin B., Actions, Lipoxin A causes dilation of minute blood vessels. Both, the types inhibit the cytotoxic effects of killer T cells., OTHER LOCAL HORMONES, SYNTHESIZED IN TISSUES, In addition to prostaglandins and related hormonal, substances, tissues secrete some more hormones, which are listed below:, 1. Acetylcholine, 2. Serotonin, 3. Histamine, 4. Substance P, 5. Heparin, 6. Leptin, 7. Gastrointestinal hormones., , Source of secretion, i. Presynaptic terminals, ii. Preganglionic parasympathetic nerve, iii. Postganglionic parasympathetic nerve, iv. Preganglionic sympathetic nerve, v. Postganglionic sympathetic cholinergic nerves, such as:, a. Nerves supplying eccrine sweat glands, b. Sympathetic vasodilator nerves in skeletal, muscle, vi. Nerves in amacrine cells of retina, vii. Mast cell, viii. Gastric mucosa, ix. Lungs, x. Many regions of brain., Actions, Acetylcholine:, i. Produces excitatory function of synapse by, opening the sodium channels, ii. Activates smooth muscles in GI tract, urinary, tract and skeletal muscles, iii. Inhibits cardiac function, iv. Causes vasodilatation., Destruction, Acetylcholine is very quick in action. Immediately, after executing the action, it is destroyed by acetylcholinesterase. This enzyme is present in basal lamina, of the synaptic cleft., 2. Serotonin, Serotonin is otherwise known as 5hydroxytryptamine., Source of secretion, Serotonin is secreted in the following structures:, i. Hypothalamus, ii. Limbic system, iii. Cerebellum, iv. Spinal cord
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450 Section 6 t Endocrinology, v., vi., vii., viii., , Retina, Gastrointestinal tract, Lungs, Platelets., , Actions, Serotonin:, i. Is an inhibitory substance (Chapter 141), ii. Inhibits impulses of pain sensation in posterior, gray horn of spinal cord, iii. Causes mood depression and induces sleep, (Chapter160), iv. Causes vasoconstriction., 3. Histamine, Source of secretion, Histamine is secreted in nerve endings of hypothalamus,, limbic cortex and other parts of cerebral cortex and, spinal cord. Histamine is also released from tissues, during allergic condition, inflammation or damage., Actions, i. It is an excitatory neurotransmitter substance, ii. Histamine released from tissues causes, vasodilatation and enhances the capillary, permeability for fluid and plasma proteins, from blood into the affected tissues. So, the, accumulation of fluid with proteins develops, local edema, iii. In GI tract, histamine increases the motility., 4. Substance P, Source of secretion, i. Nerve endings (first order neurons of pain, pathway) in spinal cord and retina (Chapters, 141 and 145), ii. GI tract (by the presence of chyme)., Actions, i. Substance P is the neurotransmitter for pain, ii. It is also the neurotransmitter substance in GI, tract. In GI tract, it increases the mixing and, propulsive movements of small intestine., 5. Heparin, Source of secretion, i. Mast cells, ii. Basophils., , Actions, Heparin is a naturally produced anticoagulant (Refer, Chapter 20 for other details)., 6. Leptin, Leptin (in Greek, it means thin) is a protein hormone, with 167 amino acids., Source of secretion, Leptin is secreted by adipocytes in adipose tissues., Actions, Leptin plays an important role in controlling the adipose, tissue and food intake. Leptin acts on hypothalamus and, inhibits the feeding center, resulting in stoppage of food, intake (Chapter 149). At the same time, it also stimulates, the metabolic reactions involved in utilization of fat, stored in adipose tissue for energy. Thus, the circulating, leptin level informs the brain about the energy storage, and the necessity to regulate metabolic reactions, food, intake and body weight., Mode of action of leptin, Refer Chapter 149 for mode of leptin and leptin, receptors., 7. Gastrointestinal Hormones, Gastrointestinal hormones are explained in Chapter, 44., , LOCAL HORMONES PRODUCED, IN BLOOD, Local hormones produced in the blood are:, 1. Serotonin, 2. Angiotensinogen, 3. Kinins., Serotonin is described above. Angiotensinogen is, explained in Chapter 50., KININS, Kinins are biologically active protein hormones which, are circulating in blood. Kinins are of two types:, 1. Bradykinin, 2. Kallidin., Along with other proteins of their family, kinins form, the kinin system or kinin-kallikrein system.
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452 Questions in Endocrinology, , QUESTIONS IN ENDOCRINOLOGY, , LONG QUESTIONS, 1. Enumerate the hormones secreted by pituitary, gland. Describe the actions and regulation of, secretion of growth hormone. Write in brief about, effects of hypersecretion of anterior pituitary, gland., 2. Give an account of hypothalamohypophyseal, relations., 3. Describe the synthesis, storage, release,, transport, functions and regulation of secretion of, thyroid hormones., 4. Explain the functions and regulation of secretion, of parathormone. Add a note on the disorders of, parathormone., 5. What is the importance of calcium in the body?, Explain the regulation of blood calcium level. Add, a note on tetany., 6. Enlist the hormones secreted by pancreas., Explain the functions and regulation of secretion, of insulin., 7. Describe in detail the regulation of blood sugar, level., 8. Classify the hormones secreted by adrenal cortex., Explain the actions and regulation of secretion of, cortisol., 9. Enumerate the corticosteroids. Describe the actions, and regulation of secretion of aldosterone., 10. What are catecholamines? Explain the synthesis,, metabolism, actions and regulation of secretion, of catecholamines., , SHORT QUESTIONS, 1., 2., 3., 4., 5., 6., 7., 8., 9., 10., 11., 12., 13., 14., 15., 16., , Mechanism of hormonal action., Mechanism of action of protein hormones., Mechanism of action of steroid hormones., Second messenger., Growth hormone., Thyroidstimulating hormone., Adrenocorticotropic hormone., Gonadotropins., Somatomedin., Oxytocin., Antidiuretic hormone., Neuroendocrine reflex., Milk ejection reflex., Disorders of anterior pituitary gland., Gigantism., Acromegaly., , 17., 18., 19., 20., 21., 22., 23., 24., 25., 26., 27., 28., 29., 30., 31., 32., 33., 34., 35., 36., 37., 38., 39., 40., 41., 42., 43., 44., 45., 46., 47., 48., 49., 50., 51., 52., 53., 54., 55., 56., 57., 58., 59., 60., 61., 62., 63., 64., 65., 66., , Dwarfism., Acromicria., Simmond disease., Fröhlich syndrome., Disorders of posterior pituitary gland., Hypothalamohypophyseal relations., Diabetes insipidus., Synthesis of thyroid hormones., Thyroglobulin., Thyroxine., Hyperthyroidism/thyrotoxicosis/Graves disease., Hypothyroidism., Goiter., Cretinism., Myxedema., Antithyroid substances., Parathormone., Tetany., Hypercalcemia/hypocalcemia., Insulin., Glucagon., Somatostatin., Diabetes mellitus., Hyperinsulinism., Cortisol., Nonmetabolic actions of cortisol., Aldosterone., Aldosterone escape., Adrenal androgens., Cushing syndrome or disease., Hyperaldosteronism., Atrial natriuretic peptide or endocrine function of, heart., Adrenogenital syndrome., Virilism., Addison disease., Addisonian crisis., Synthesis of catecholamines., Actions of catecholamines., Adrenergic receptors., Dopamine., Pheochromocytoma., Functions of pineal gland., Melatonin., Functions of thymus., Endocrine functions of kidney., Local hormones., Prostaglandins., Acetylcholine., Leptin., Kinins.
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Section, , 7, , 74., 75., 76., 77., 78., 79., 80., 81., 82., 83., 84., 85., 86., 87., 88., , Reproductive, System, , Male Reproductive System ..................................................................... 455, Seminal Vesicles ..................................................................................... 467, Prostate Gland ........................................................................................ 468, Semen ..................................................................................................... 470, Female Reproductive System ................................................................. 473, Ovary ....................................................................................................... 476, Menstrual Cycle ...................................................................................... 482, Ovulation ................................................................................................. 492, Menopause ............................................................................................. 494, Infertility .................................................................................................. 496, Pregnancy and Parturition ....................................................................... 498, Placenta .................................................................................................. 505, Pregnancy Tests ...................................................................................... 508, Mammary Glands and Lactation ............................................................. 510, Fertility Control ........................................................................................ 513
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Male Reproductive System, , Chapter, , 74, , INTRODUCTION, FUNCTIONAL ANATOMY OF TESTES, , , , , COVERINGS, PARENCHYMA, SEMINIFEROUS TUBULES, , FUNCTIONS OF TESTES, GAMETOGENIC FUNCTIONS OF TESTES – SPERMATOGENESIS, , , , STAGES OF SPERMATOGENESIS, FACTORS AFFECTING SPERMATOGENESIS, , ENDOCRINE FUNCTIONS OF TESTES, , , , , , , , , HORMONES SECRETED BY TESTES, TESTOSTERONE SECRETION IN DIFFERENT PERIODS OF LIFE, FUNCTIONS OF TESTOSTERONE, MODE OF ACTION OF TESTOSTERONE, REGULATION OF TESTOSTERONE SECRETION, ANABOLIC STEROIDS, PRODUCTION OF FEMALE SEX HORMONES IN MALES, , MALE ANDROPAUSE OR CLIMACTERIC, APPLIED PHYSIOLOGY, , , , , EFFECTS OF EXTIRPATION OF TESTES, HYPERGONADISM IN MALES, HYPOGONADISM IN MALES, , ACCESSORY SEX ORGANS IN MALES, , INTRODUCTION, Reproductive system ensures the continuation of, species. Gonads are the primary reproductive organs, , which produce the gametes (egg or ovum); a pair of, testes (singular = testis) produces sperms in males and, a pair of ovaries produces ovum in females., Normally, most of the animals including humans, are either definite males or definite females. However,, in some organisms like earthworms and snails, both, sexes may be present in the same organism and this, condition is known as hermaphroditism., In humans and most of the higher animals,, reproduction occurs sexually, i.e. by mating. However,, , there are some species like insects which can produce, offsprings without mating., Reproductive organs include:, 1. Primary sex organs, 2. Accessory sex organs., Primary Sex Organs, Testes are the primary sex organs or gonads in males., Accessory Sex Organs, Accessory sex organs in males are:, 1. Seminal vesicles, 2. Prostate gland
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456 Section 7 t Reproductive System, 3. Urethra, 4. Penis., External and Internal Genitalia, Reproductive organs are generally classified into two, groups, namely external genitalia (genital organs) and, internal genitalia. External genital organs in males are, scrotum, penis and urethra. Remaining sex organs, constitute the internal genitalia., , Thus, there are two ejaculatory ducts each of which, receives sperm from vas deferens and secretions of, seminal vesicle on its own side. Both the ejaculatory, ducts empty into a single urethra. Actually, ejaculatory, ducts open into prostatic part of urethra., COVERINGS OF TESTIS, Each testis is enclosed by three coverings., 1. Tunica Vasculosa, , FUNCTIONAL ANATOMY OF TESTES, Testes are the primary sex organs or gonads in males., There are two testes in almost all the species. In human, beings, both the testes are ovoid or walnut-shaped, bodies that are located and suspended in a sac-like, structure called scrotum., Each testis weighs about 15 to 19 g and measures, about 5 × 3 cm. Testis is made up of about 900 coiled, tubules known as seminiferous tubules, which produce, sperms. Seminiferous tubules continue as the vas, efferens, which form the epididymis. It is continued as, vas deferens., , Vas deferens is also called ductus deferens,, spermatic deferens or sperm duct. From epididymis, in scrotum, the vas deferens extends on its one side, upwards into abdominal cavity via inguinal canal., Terminal portion of vas deferens is called ampulla (Fig., 74.1). Ampulla of vas deferens joins ducts of seminal, vesicle of same side, to form ejaculatory duct., , Tunica vasculosa is the innermost covering. It is made, up of connective tissue and it is rich in blood vessels, 2. Tunica Albuginea, Tunica albuginea is the middle covering. It is a dense, fibrous capsule, 3. Tunica Vaginalis, Tunica vaginalis is the outermost closed cleft like, covering, formed by mesothelial cells. It is formed by, visceral and parietal layers, which glide on one another, and allow free movement of testes. Visceral layer of, tunica vaginalis adheres to tunica albuginea and the, parietal layer lines the inner surface of the scrotum., Anterior and lateral surfaces of testis are covered, by all the three layers. Posterior surface is covered by, tunica albuginea only., PARENCHYMA OF TESTIS, Lobules of Testis, Tunica albuginea on the posterior surface of testis is, thickened to form the mediastinum testis. From this,, the connective tissue septa called septula testis radiate, into testis and bind with tunica albuginea at various, points. Because of this, testis is divided into a number, of pyramidal lobules, with bases directed towards the, periphery and the apices towards the mediastinum, (Fig. 74.2)., The septula do not form complete partition so the, lobules of testis anastomose with one another at many, places. Each testis has about 200 to 300 lobules., Seminiferous Tubules, , FIGURE 74.1: Male reproductive system and, other organs of pelvis, , Each lobule contains 1 to 4 coiled tubules known, as the seminiferous tubules, which are surrounded, and supported by interlobular connective tissue., Seminiferous tubules do not end bluntly, but form single,, double or triple arches. Limbs of an arch are not in the, same lobule (fig. 74.2). Other details of seminiferous, tubules are given below.
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Chapter 74 t Male Reproductive System 457, Wall of the seminiferous tubule is formed by three, layers:, 1. Outer capsule or tunica propria, formed by fibroelastic connective tissue, 2. Thin homogeneous basement membrane, 3. Complex stratified epithelium, which consists of two, types of cells:, i. Spermatogenic cells or germ cells, ii. Sertoli cells or supporting cells., Spermatogenic Cells, , FIGURE 74.2: Structure of testis, , Rete Testis, Rete testis is a network of thin-walled channels present, in mediastinum. All the seminiferous tubules open into, the rete testis., Vas Efferens, From rete testis, 8 to 15 tubules called vas efferens, arise. Vas efferens join together and form the head, of epididymis and then converge to form the duct of, epididymis (Fig. 74.3)., , Spermatogenic cells or germ cells present in seminiferous, tubules are precursor cells of spermatozoa. These, cells lie in between Sertoli cells and are arranged in an, orderly manner in 4 to 8 layers., In children, the testis is not fully developed. Therefore,, the spermatogenic cells are in primitive stage called, spermatogonia. With the onset of puberty, spermatogonia, develop into sperms through different stages., Stages of spermatogenic cells, Different stages of spermatogenic cells seen from, periphery to the lumen of seminiferous tubules are:, 1. Spermatogonium, 2. Primary spermatocyte, 3. Secondary spermatocyte, 4. Spermatid., , Epididymis, Duct of epididymis is an enormously convoluted tubule,, with a length of about 4 meter. It begins at head, where, it receives vas efferens., Vas Deferens, At the caudal pole of testis, epididymis turns sharply, upon itself and continues as vas deferens, without any, definite demarcation., Interstitial Cells of Leydig, Interstitial cells of Leydig are the hormone secreting cells, of testis, lying in between the seminiferous tubules., SEMINIFEROUS TUBULES, Seminiferous tubules are thread-like convoluted tubular, structures which produce the spermatozoa or sperms., There are about 400 to 600 seminiferous tubules in each, testis. Each tubule is 30 to 70 cm long with a diameter, of 150 to 300 µ., , FIGURE 74.3: Pathway for the passage of sperms
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458 Section 7 t Reproductive System, Sertoli Cells, Sertoli cells are the supporting cells for spermatogenic, cells in seminiferous tubules. These cells are also called, sustentacular cells or nurse cells., Sertoli cells are the large and tall irregular columnar, cells, extending from basement membrane to lumen, of the seminiferous tubule. Germ cells present in, seminiferous tubule are attached to Sertoli cells by, means of cytoplasmic connection. This attachment, between germ cells and Sertoli cells exists till the, matured spermatozoa are released into the lumen of, seminiferous tubules., Functions of Sertoli cells, Sertoli cells provide support, protection and nourishment, for the spermatogenic cells present in seminiferous, tubules., Sertoli cells:, 1. Support and nourish the spermatogenic cells till the, spermatozoa are released from them, 2. Secrete the enzyme aromatase, which converts, androgens into estrogen, 3. Secrete androgen-binding protein (ABP), which is, essential for testosterone activity, especially during, spermatogenesis, 4. Secrete estrogen-binding protein (EBP), 5. Secrete inhibin, which inhibits FSH release from, anterior pituitary, 6. Secrete activin, which has opposite action of inhibin, (increases FSH release), 7. Secrete müllerian regression factor (MRF) in fetal, testes. MRF is also called müllerian inhibiting, substance (MIS). MRF is responsible for the, regression of müllerian duct during sex differentiation, in fetus., Blood-testes Barrier, Blood-testes barrier is a mechanical barrier that separates blood from seminiferous tubules of the testes. It is, formed by tight junctions between the adjacent Sertoli, cells, near the basal membrane of seminiferous tubule., Functions of blood-testes barrier, 1. Protection of seminiferous tubules, Blood-testes barrier protects the seminiferous tubules, and spermatogenic cells by preventing the entry of toxic, substances from blood and fluid of the surrounding, tissues into the lumen of seminiferous tubules. However,, blood-testes barrier permits substances essential for, spermatogenic cells., , Substances prevented by blood-testes barrier:, i. Large molecules including proteins, polysaccharides and cytotoxic substances, ii. Medium-sized molecules like galactose., Substances permitted by blood-testes barrier:, i. Nutritive substances essential for spermatogenic, cells, ii. Hormones necessary for spermatogenesis, iii. Water., 2. Prevention of autoimmune disorders, Blood-testes barrier also prevents the development of, autoimmune disorders by inhibiting the movement of, antigenic products of spermatogenesis, from testis into, blood., Damage of blood-testes barrier, Blood-testes barrier is commonly damaged by trauma, or viral infection like mumps. Whenever, the bloodtestes barrier is damaged the sperms enter the blood., The immune system of the body is activated, resulting in, the production of autoantibodies against sperms. The, antibodies destroy the germ cells, leading to consequent, sterility., , FUNCTIONS OF TESTES, Testes performs two functions:, 1. Gametogenic function: Spermatogenesis, 2. Endocrine function: Secretion of hormones., , GAMETOGENIC FUNCTIONS, OF TESTES – SPERMATOGENESIS, Spermatogenesis is the process by which the male, gametes called spermatozoa (sperms) are formed from, the primitive spermatogenic cells (spermatogonia) in, the testis (Fig. 74.4). It takes 74 days for the formation, of sperm from a primitive germ cell. Throughout, the process of spermatogenesis, the spermatogenic, cells have cytoplasmic attachment with Sertoli cells., Sertoli cells supply all the necessary materials for, spermatogenesis through the cytoplasmic attachment., STAGES OF SPERMATOGENESIS, Spermatogenesis occurs in four stages:, 1. Stage of proliferation, 2. Stage of growth, 3. Stage of maturation, 4. Stage of transformation.
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Chapter 74 t Male Reproductive System 459, , FIGURE 74.4: Spermatogenesis. Number in parenthesis indicate chromosomal number, , 1. Stage of Proliferation, , 3. Stage of Maturation, , Each spermatogonium contains diploid number (23, pairs) of chromosomes. One member of each pair is, from maternal origin and the other one from paternal, origin. The 23 pairs include 22 pairs of autosomal, chromosomes and one pair of sex chromosomes., Sex chromosomes are one X chromosome and one Y, chromosome., During the proliferative stage, spermatogonia, divide by mitosis, without any change in chromosomal, number. In man, there are usually seven generations of, spermatogonia. The last generation enters the stage of, growth as primary spermatocyte., During this stage, the spermatogonia migrate along, with Sertoli cells towards the lumen of seminiferous, tubule., , After reaching the full size, each primary spermatocyte, quickly undergoes meiotic or maturation division, which, occurs in two phases:, , 2. Stage of Growth, In this stage, the primary spermatocyte grows into a, large cell. Apart from growth, there is no other change, in spermatocyte during this stage., , First phase, In the first phase, each primary spermatocyte divides, into two secondary spermatocytes. The significance, of the first meiotic division is that each secondary, spermatocyte receives only the haploid or half the, number of chromosomes. 23 chromosomes include 22, autosomes and a X or a Y chromosome., Second phase, During this phase, each secondary spermatocyte undergoes second meiotic division, resulting in two smaller, cells called spermatids. Each spermatid has haploid, number of chromosomes., 4. Stage of Transformation, There is no further division. Spermatids are transformed, into matured spermatozoa (sperms), by means of, spermeogenesis and released by spermination.
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460 Section 7 t Reproductive System, Spermeogenesis, Spermeogenesis is the process by which spermatids, become matured spermatozoa., Changes taking place during spermeogenesis:, i. Condensation of nuclear material, ii. Formation of acrosome, mitochondrial spiral, filament and tail structures, iii. Removal of extraneous (extra volume of, nonessential) cytoplasm., , cells and spermatogonia and induces the proliferation, of spermatogonia. It also stimulates the formation of, estrogen and androgen-binding protein from Sertoli, cells (Fig. 74.5)., ii. Testosterone, Testosterone is responsible for the sequence of remaining, stages in spermatogenesis. It is also responsible for the, maintenance of spermatogenesis. Testosterone activity, is largely influenced by androgen-binding protein., , Spermination, , iii. Estrogen, , Spermination is the process by which the matured, sperms are released from Sertoli cells into the lumen of, seminiferous tubules., Refer Chapter 77 for structure of sperm., , Estrogen is formed from testosterone in Sertoli cells. It, is necessary for spermeogenesis., , FACTORS AFFECTING SPERMATOGENESIS, Spermatogenesis is influenced by:, 1. Sertoli cells, 2. Hormones, 3. Other factors., 1. Role of Sertoli Cell in Spermatogenesis, Sertoli cells influence spermatogenesis by:, i. Supporting and nourishing the germ cells, ii. Providing hormonal substances necessary for, spermatogenesis, iii. Secreting androgen-binding protein (ABP),, which is essential for testosterone activity,, particularly on spermatogenesis, iv. Releasing sperms into the lumen of seminiferous, tubules (spermination)., 2. Role of Hormones in Spermatogenesis, Spermatogenesis is influenced by many hormones,, which act either directly or indirectly: Table 74.1, gives the hormones essential for each stage of, spermatogenesis., Hormones necessary for spermatogenesis are:, i. Follicle-stimulating hormone (FSH), ii. Testosterone, iii. Estrogen, iv. Luteinizing hormone (LH), v. Growth hormone (GH), vi. Inhibin, vii. Activin., i. Follicule-stimulating hormone, Follicule-stimulating hormone is responsible for the, initiation of spermatogenesis. It binds with Sertoli, , iv. Luteinizing Hormone, In males, this hormone is called interstitial cellstimulating hormone. It is essential for the secretion of, testosterone from Leydig cells., v. Growth Hormone, Growth hormone is essential for the general metabolic, processes in testis. It is also necessary for the proliferation of spermatogonia. In pituitary dwarfs, the, spermatogenesis is severely affected., vi. Inhibin, Inhibin is a peptide hormone and serves as a transforming, growth factor. It is secreted by Sertoli cells. In females,, it is secreted by granulosa cells of ovarian follicles. Its, secretion is stimulated by FSH., Inhibin plays an important role in the regulation of, spermatogenesis by inhibiting FSH secretion through, feedback mechanism. FSH secreted from anterior, pituitary induces spermatogenesis by stimulating Sertoli, cells. It also stimulates the secretion of inhibin from, Sertoli cells. So, when the rate of spermatogenesis, increases, there is a simultaneous increase in inhibin, secretion also. Inhibin in turn, acts on anterior pituitary, and inhibits the secretion of FSH, leading to decrease in, the pace of spermatogenesis., TABLE 74.1: Hormones necessary for spermatogenesis, Stage of spermatogenesis, , Hormones necessary, , Stage of proliferation, , Follicle-stimulating hormone, Growth hormone, , Stage of growth, , Testosterone, Growth hormone, , Stage of maturation, , Testosterone, Growth hormone, , Stage of transformation, , Testosterone, Estrogen
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Chapter 74 t Male Reproductive System 461, In cryptorchidism, the testes are in the abdomen,, where the temperature is always higher than that of, scrotum. High temperature in the abdomen causes, degeneration of seminiferous tubules and stoppage of, spermatogenesis., ii. Diseases, Infectious diseases such as mumps cause degeneration of, seminiferous tubules and stoppage of spermatogenesis., , ENDOCRINE FUNCTIONS OF TESTES, HORMONES SECRETED BY TESTES, Testes secrete male sex hormones, which are collectively, called the androgens., Androgens secreted by testes are:, 1. Testosterone, 2. Dihydrotestosterone, 3. Androstenedione., Among these three androgens, testosterone, is secreted in large quantities. However, dihydrotestosterone is more active., Female sex hormones, namely estrogen and, progesterone are also found in testes. Two more, hormones activin and inhibin are also secreted in testes., However, these two hormones do not have androgenic, FIGURE 74.5: Role of hormones in spermatogenesis. Blue, arrow = Stimulation, Red dotted arrow = inhibition, GnRH =, Gonadotropin-releasing hormone, FSH = Follicle-stimulating, hormone, LH = Lutinizing hormone, GH = Growth hormone., , It is believed that inhibin also inhibits FSH, secretion indirectly by inhibiting GnRH secretion from, hypothalamus., vii. Activin, Activin is also a peptide hormone secreted in gonads, along with inhibin. The exact location of its secretion in, testis is not known. It is suggested that activin is secreted, by Sertoli cells and Leydig cells., Activin has opposite actions of inhibin. It increases the, secretion of FSH and accelerates spermatogenesis., 3. Role of Other Factors in Spermatogenesis, i. Increase in body temperature, Increase in body temperature prevents spermatogenesis. Normally, the temperature in scrotum is, about 2°C less than the body temperature. This low, temperature is essential for spermatogenesis. When the, temperature increases, the spermatogenesis stops. It is, very common in cryptorchidism (undescended testes)., , actions., , Source of Secretion of Androgens, Androgens are secreted in large quantities by testes, and in small quantity by adrenal cortex., Testes, In testes, androgens are secreted by the interstitial, cells of Leydig, which form 20% of mass of adult testis., Leydig cells are numerous in newborn male baby and in, adult male. But in childhood, these cells are scanty or, nonexisting. So, the secretion of androgens occurs in, newborn babies and after puberty., Adrenal cortex, Androgens secreted by zona reticularis of adrenal, cortex are testosterone, androstenedione and, dehydroepiandrosterone. Adrenal androgens do not, have any significant physiological actions because, of their small quantity. In abnormal conditions, the, hypersecretion of adrenal androgens results in sexual, disorders (Chapter 70)., Chemistry, Testosterone is a C19 steroid.
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462 Section 7 t Reproductive System, Synthesis, Androgens are steroid hormones synthesized from, cholesterol. Androgens are also synthesized directly, from acetate. Synthesis of male sex hormones is given, in Fig. 70.2, Chapter 70., Plasma Level and Transport, Plasma level of testosterone in an adult male varies, between 300 and 700 ng/dL. In adult female, the, testosterone level is 30 to 60 mg/dL., Two thirds of testosterone is transported in plasma, by gonadal steroid-binding globulin. It is β-globulin in, nature and it is also called sex steroid-binding globulin., The remaining one third of testosterone is transported, by albumin., Metabolism, In many target tissues, testosterone is converted, into dehydrotestosterone, which is the most active, androgen. In some of the tissues such as adipose tissue,, hypothalamus and liver, testosterone is converted into, estradiol. Major portion of testosterone is degraded in, liver. It is converted into inactive forms of androsterone, and dehydroepiandrosterone. These two substances, are later conjugated and excreted through urine., TESTOSTERONE SECRETION, IN DIFFERENT PERIODS OF LIFE, Testosterone secretion starts at 7th week of fetal life, by fetal genital ridge. Fetal testes begin to secrete, testosterone at about 2nd to 4th month of fetal life. In fetal, life, testosterone secretion from testes is stimulated by, human chorionic gonadotropins, secreted by placenta., But in childhood, practically no testosterone is, secreted approximately until 10 to 12 years of age., Afterwards, the testosterone secretion starts and it, increases rapidly at the onset of puberty and lasts, through most of the remaining part of life. The secretion, starts decreasing after 40 years and becomes almost, zero by the age of 90 years (Fig. 74.6)., FUNCTIONS OF TESTOSTERONE, In general, testosterone is responsible for the, distinguishing characters of masculine body. It also, plays an important role in fetal life., Functions of Testosterone in Fetal Life, Testosterone performs three functions in fetus:, 1. Sex differentiation in fetus, , FIGURE 74.6: Plasma testosterone in different, ages of male humans, , 2. Development of accessory sex organs, 3. Descent of the testes., 1. Sex differentiation in fetus, Sex chromosomes are responsible for the determination, of sex of the fetus (Chapter 84), whereas testosterone is, responsible for the sex differentiation of fetus., Fetus has two genital ducts:, i. Müllerian duct, which gives rise to female, accessory sex organs such as vagina, uterus, and fallopian tube, ii. Wolffian duct, which gives rise to male accessory, sex organs such as epididymis, vas deferens, and seminal vesicles., If testosterone is secreted from the genital ridge, of the fetus at about 7th week of intrauterine life,, the müllerian duct system disappears and male sex, organs develop from Wolffian duct., In addition to testosterone, müllerian regression, factor (MRF) secreted by Sertoli cells is also responsible for regression of müllerian duct., In the absence of testosterone, Wolffian duct, regresses and female sex organs develop from, müllerian duct.
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Chapter 74 t Male Reproductive System 463, 2. Development of accessory sex organs, and external genitalia, Testosterone is also essential for the growth of the, external genitalia, viz. penis and scrotum and other, accessory sex organs, namely genital ducts, seminal, vesicles and prostate., 3. Descent of testes, Descent of testes is the process by which testes enter, scrotum from abdominal cavity. Initially, testes are, developed in the abdominal cavity and are later pushed, down into the scrotum through inguinal canal, just, before birth. The process by which testes enter the, scrotum is called the descent of testes. Testosterone is, necessary for descent of testes., Cryptorchidism, Cryptorchidism is a congenital disorder characterized, by the failure of one or both the testes to descent from, abdomen into scrotum. In such case, the testes are, called undescended testes. Males with untreated testes, are prone for testicular cancer., Treatment, Administration of testosterone or gonadotropic, hormones (which stimulate Leydig cells) causes, descent of testes, provided the inguinal canal is large, enough to allow the passage of testes. Surgery is, required if the inguinal canal is narrow., Functions of Testosterone in Adult Life, Testosterone has two important functions in adult:, 1. Effect on sex organs, 2. Effect on secondary sexual characters., 1. Effect on sex organs, Testosterone increases the size of penis, scrotum and, the testes after puberty. All these organs are enlarged, at least 8 folds between the onset of puberty and the, age of 20 years, under the influence of testosterone., Testosterone is also necessary for spermatogenesis., 2. Effect on secondary sexual characters, Secondary sexual characters are the physical and, behavioral characteristics that distinguish the male, from female. These characters appear at the time of, puberty in humans. Testosterone is responsible for the, development of secondary sexual characters in males., , Secondary sexual characters in males:, i. Effect on muscular growth, One of the most important male sexual characters is the, development of musculature after puberty. Muscle mass, increases by about 50%, due to the anabolic effect of, testosterone on proteins. Testosterone accelerates the, transport of amino acids into the muscle cells, synthesis, of proteins and storage of proteins. Testosterone also, decreases the breakdown of proteins., ii. Effect on bone growth, After puberty, testosterone increases the thickness of, bones by increasing the bone matrix and deposition of, calcium. It is because of the protein anabolic activity of, testosterone. Deposition of calcium is secondary to the, increase in bone matrix., In addition to increase in the size and strength, of bones, testosterone also causes early fusion of, epiphyses of long bones with shaft. So, if testes are, removed before puberty, the fusion of epiphyses is, delayed and the height of the person increases., iii. Effect on shoulder and pelvic bones, Testosterone causes broadening of shoulders and it has, a specific effect on pelvis, which results in:, a. Lengthening of pelvis, b. Funnel-like shape of pelvis., c. Narrowing of pelvic outlet., Thus, pelvis in males is different from that of females,, which is broad and round or oval in shape., iv. Effect on skin, Testosterone increases the thickness of skin and, ruggedness of subcutaneous tissue. These changes, in skin are due to the deposition of proteins in skin. It, also increases the quantity of melanin pigment, which is, responsible for the deepening of the skin color., Testosterone enhances the secretory activity of, sebaceous glands. So, at the time of puberty, when the, body is exposed to sudden increase in testosterone, secretion, the excess secretion of sebum leads to, development of acne on the face. After few years, the, skin gets adapted to testosterone secretion and the, acne disappears., v. Effect on hair distribution, Testosterone causes male type of hair distribution on, the body, i.e. hair growth over the pubis, along linea, alba up to umbilicus, on face, chest and other parts of, the body such as back and limbs. In males, the pubic
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464 Section 7 t Reproductive System, hair has the base of the triangle downwards where as in, females it is upwards. Testosterone decreases the hair, growth on the head and may cause baldness, if there is, genetic background., , REGULATION OF, TESTOSTERONE SECRETION, , vi. Effect on voice, , During fetal life, the testosterone secretion from testes, is stimulated by human chorionic gonadotropin,, which has the properties similar to those of luteinizing, hormone. Human chorionic gonadotropin stimulates, the development of Leydig cells in the fetal testes and, promotes testosterone secretion., , At the time of adolescence, the boys have a cracking, voice. It is because of the testosterone effect, which, causes:, a. Hypertrophy of laryngeal muscles, b. Enlargement of larynx and lengthening, c. Thickening of vocal cords., Later, the cracking voice changes gradually into a, typical adult male voice with a bossing sound., vii. Effect on basal metabolic rate, At the time of puberty and earlier part of adult life,, the testosterone increases the basal metabolic rate, to about 5% to 10% by its anabolic effects on protein, metabolism., , In Fetus, , In Adults, Luteinizing hormone (LH) or interstitial cell stimulating, , hormone (ICSH) stimulates the Leydig cells and the, quantity of testosterone secreted is directly proportional, to the amount of LH available., Secretion of LH from anterior pituitary gland is, stimulated by luteinizing hormone releasing hormone, (LHRH) from hypothalamus., , viii. Effect on electrolyte and water balance, , Feedback Control, , Testosterone increases the sodium reabsorption from, renal tubules, along with water reabsorption. It leads to, increase in ECF volume., , Testosterone regulates its own secretion by negative, feedback mechanism. It acts on hypothalamus and, , ix. Effect on blood, Testosterone has got erythropoietic action. So, after, puberty, testosterone causes mild increase in RBC, count. It also increases the blood volume by increasing, the water retention and ECF volume., MODE OF ACTION OF TESTOSTERONE, Testosterone combines with receptor proteins. The, testosterone-receptor complex migrates to nucleus,, binds with a nuclear protein and induces the DNA-RNA, transcription process. In 30 minutes, the RNA polymer, is activated and the concentration of RNA increases., The quantity of DNA also increases., So, the testosterone primarily stimulates the protein, synthesis in the target cells, which are responsible for, the development of secondary sexual characters., Testosterone is converted into dihydrotestosterone, (DHT) in the target cells of some accessory sex, organs such as epididymis and penis. DHT combines, with receptor proteins and the DHT-receptor complex, induces the DNA-RNA transcription process. DHTreceptor complex is more stable than testosteronereceptor complex., In brain, testosterone is converted into estrogen, (estradiol)., , inhibits the secretion of LHRH. When LHRH secretion, is inhibited, LH is not released from anterior pituitary,, resulting in stoppage of testosterone secretion from, testes. On the other hand, when testosterone production, is low, lack of inhibition of hypothalamus leads to secretion of testosterone through LHRH and LH (Fig. 74.7)., ANABOLIC STEROIDS, Anabolic steroids are the synthetic forms of testosterone,, which are used to increase the growth of muscles and, bones. Like androgens, these steroids also increase, the growth of muscles and bones by accelerating, protein synthesis (anabolic effect). These drugs are, also called anabolic-androgenic steroids (AAS)., Therapeutic Uses of Anabolic Steroids, 1., 2., 3., 4., , Growth stimulation, Bone marrow stimulation, Hormone replacement therapy, Induction of puberty in males., , Abuse of Anabolic Steroids, Anabolic steroids are commonly used by athletes, to improve their performances during competitions,, particularly in professional sports. Organizations of, many sports have banned the use of anabolic steroids, by their athletes.
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Chapter 74 t Male Reproductive System 465, Progesterone, Progesterone is also produced from androgens in males, though the quantity is very less. Plasma progesterone, level in normal adult male is 0.3 ng/mL., , MALE ANDROPAUSE OR CLIMACTERIC, Male andropause or climacteric is the condition in men,, characterized by emotional and physical changes in the, body, due to low androgen level with aging. It is also, called viropause., After the age of 50, testosterone secretion starts, declining. It is accompanied by decrease in number and, secretory activity of Leydig cells. Low level of testosterone, increases the secretion of FSH and LH, which leads, to some changes in the body. It does not affect most, of the men. But some men develop symptoms similar, to those of female menopausal syndrome (Chapter, 82). Common symptoms are hot flashes, illusions of, suffocation and mood changes., , APPLIED PHYSIOLOGY, EFFECTS OF EXTIRPATION OF TESTES, FIGURE 74.7: Regulation of testosterone secretion. LHRH =, Luteinizing hormone-releasing hormone, ICSH = Interstitial, cell-stimulating hormone., , PRODUCTION OF FEMALE, SEX HORMONES IN MALES, In addition to androgens, female sex hormones are also, produced in testes., Estrogen, Small amount of estrogen is produced in males. Estrogen, level in plasma of normal adult male is 12 to 34 pg/mL., Estrogens have three sources of production in males., 1. Adrenal Cortex, , Extirpation (removal) of testes is called castration., Effects of castration depend upon the age when testes, are removed., 1. Effects of Extirpation of Testes, before Puberty – Eunuchism, If a boy looses the testes before puberty, he continues, to have infantile sexual characters throughout his life, and this condition is called eunuchism. Height of the, person is slightly more but the bones are weak and thin., Muscles become weak and shoulder remains narrow., Sex organs do not increase in size and the male, secondary sexual characters do not develop. The voice, remains like that of a child., There is abnormal deposition of fat on buttocks, hip,, pubis and breast, resembling the feminine distribution., , Adrenal cortex secretes small quantity of estrogen., Refer Chapter 70 for details., , 2. Effects of Extirpation of Testes, Immediately after Puberty, , 2. Testes, , If testes are removed after puberty, some of the male, secondary sexual characters revert to those of a child, and other masculine characters are retained., Sex organs are depressed. Seminal vesicles and, prostate undergo atrophy. Penis remains smaller. Voice, remains mostly masculine but other secondary sexual, characters like masculine hair distribution, musculature, and thickness of bones are lost. There may be loss of, sexual desire and sexual activities., , Up to 20% of estrogen in males is produced in testes., Estrogen is formed from androgens in Sertoli cells of, testes, by the influence of the enzyme aromatase., 3. Other Organs, About 80% of estrogen is formed from androgens in, other organs, particularly liver.
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466 Section 7 t Reproductive System, 3. Effect of Extirpation of Testes in Adults, , Before puberty, , Removal of testes in adults does not cause loss of, secondary sexual characters. But, accessory sex organs, start degenerating. The sexual desire is not totally, lost. Erection occurs but ejaculation is rare because, of degeneration of accessory sex organs and lack of, sperms., , Features of hypogonadism are similar to those, developed due to extirpation of testes before puberty,, which are described above., , HYPERGONADISM IN MALES, Hypergonadism is the condition characterized by, hypersecretion of sex hormones from gonads., Cause, Hypergonadism in males is mainly due to the tumor, of Leydig cells. It is common in prepubertal boys who, develop precocious pseudopuberty., , After puberty, Symptoms are similar to those developed due to the, removal of testes after puberty (see above)., In adults, Same symptoms, which develop after extirpation of, testes, occur in this condition., Hypogonadism caused by testicular disorders, increases the gonadotropin secretion and the, condition is called hypergonadotropic hypogonadism., Hypogonadism that occurs due to deficiency of, gonadotropins (pituitary or hypothalamic disorder) is, called hypogonadotropic hypogonadism., , Symptoms, There is a rapid growth of musculature and bones., But, the height of the person is less because of early, closure of epiphysis. There is excess development of, sex organs and secondary sexual characters., The tumors also secrete estrogenic hormones, which, cause gynecomastia (the enlargement of breasts)., HYPOGONADISM IN MALES, , Fröhlich Syndrome, Fröhlich syndrome is the disorder characterized by, obesity and hypogonadism in adolescent boys. It is, also called adiposogenital syndrome or hypothalamic, eunuchism. Refer Chapter 66 for details., , ACCESSORY SEX ORGANS IN MALES, , Hypogonadism is a condition characterized by reduction, in the functional activity of gonads., , Seminal Vesicles, , Causes, , Prostate gland, , Hypogonadism in males is due to various abnormalities, of testes:, 1. Congenital nonfunctioning of testes, 2. Under-developed testes due to absence of human, chorionic gonadotropins in fetal life, 3. Cryptorchidism, associated with partial or total, degeneration of testes, 4. Castration, 5. Absence of androgen receptors in testes, 6. Disorder of the gonadotropes (cells secreting gonadotropins) in anterior pituitary, 7. Hypothalamic disorder., , Prostate gland is explained in Chapter 76., , Signs and Symptoms, Clinical picture of male hypogonadism depends upon, whether the testicular deficiency develops before or, after puberty., , Seminal vesicles are explained in Chapter 75., , Urethra, Urethra in male has both reproductive and urinary, functions. Refer Chapter 57 for details of urethra. Urethra, contains mucus glands throughout its length, which, are called glands of Littre. The bilateral bulbourethral, glands or Cowper glands also open into the urethra., Penis, Penis is the male genital organ. Urethra passes through, penis and opens to the exterior. Penis is formed by three, erectile tissue masses, i.e. a paired corpora cavernosa, and an unpaired corpus spongiosum. Corpus, spongiosum surrounds the urethra and terminates, distally to form glans penis.
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Chapter, , Seminal Vesicles, , 75, , STRUCTURE OF SEMINAL VESICLES, PROPERTIES AND COMPOSITION OF SEMINAL FLUID, , , , PROPERTIES, COMPOSITION, , FUNCTIONS OF SEMINAL FLUID, , , , , NUTRITION TO SPERMS, CLOTTING OF SEMEN, FERTILIZATION, , STRUCTURE OF SEMINAL VESICLES, Seminal vesicles are the paired glands situated in, lower abdomen on either side of prostate gland behind, urinary bladder. Each seminal vesicle is a hollow sac of, irregular shape and is lined by complexly folded mucous, membrane., Epithelial cells of the mucous membrane are, secretory in nature and secrete seminal fluid. Duct of, seminal vesicle from each side joins with ampulla of vas, deferens to form ejactulatory duct. Thus seminal fluid is, emptied into ejaculatory ducts, which open into urethra., Refer Chapter 57 for details., , PROPERTIES AND COMPOSITION, OF SEMINAL FLUID, PROPERTIES, Seminal fluid is mucoid and viscous in nature. It is, neutral or slightly alkaline in reaction. It adds to the bulk, of semen as it forms 60% of the total semen., COMPOSITION, Seminal vesicles secrete several important substances., Refer Figure 77.1 for the products of seminal fluid., , FUNCTIONS OF SEMINAL FLUID, NUTRITION TO SPERMS, Fructose and other nutritive substances in seminal, fluid are utilized by sperms after being ejaculated into, the female genital tract., , CLOTTING OF SEMEN, Immediately after ejaculation, semen clots because, of the conversion of fibrinogen from seminal fluid into, fibrin., FERTILIZATION, Prostaglandin of seminal fluid enhances fertilization of, ovum by:, 1. Increasing the receptive capacity of cervical, mucosa for sperms, 2. Initiating reverse peristaltic movement of uterus, and fallopian tubes. This in turn, increases the, rate of transport of sperms in female genital, tract during coitus (oxytocin is also responsible, for this process).
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Chapter, , Prostate Gland, , 76, , STRUCTURE OF PROSTATE GLAND, PROPERTIES AND COMPOSITION OF PROSTATIC FLUID, , , , PROPERTIES, COMPOSITION, , FUNCTIONS OF PROSTATIC FLUID, , , , , MAINTENANCE OF SPERM MOTILITY, CLOTTING OF SEMEN, LYSIS OF COAGULUM, , APPLIED PHYSIOLOGY – ENLARGEMENT OF, PROSTATE GLAND, , STRUCTURE OF PROSTATE GLAND, Human prostate gland weighs about 40 g. It consists, of 20 to 30 separate glands, which open separately, into the urethra. These glands are tubuloalveolar in, nature. Epithelial lining of these glands is made up of, columnar cells. Prostate secretes prostatic fluid, which, is emptied into prostatic urethra through prostatic, sinuses (Chapter 57)., , less than 6.0. There are some factors, which decrease, the pH and motility of sperm both in vas deferens and, female genital tract., In vas deferens, End products of metabolic activities in the sperm make, the fluid in vas deferens acidic, so that the sperms are, nonmotile., In female genital tract, , PROPERTIES AND COMPOSITION, OF PROSTATIC FLUID, PROPERTIES, Prostate fluid is a thin, milky and alkaline fluid. It forms, 30% of total semen., , Vaginal secretions in females are highly acidic with a pH, of 3.5 to 4.0. So, when semen is ejaculated into female, genital tract at coitus, sperms are nonmotile initially., However, the alkaline prostatic secretion, which is, also present in semen neutralizes the acidity in vagina, and maintains a pH of 6.0 to 6.5. At this pH, the sperms, become motile and chances of fertilization are enhanced., , COMPOSITION, Refer Figure 77.1 for the products secreted by prostate, gland., , CLOTTING OF SEMEN, , FUNCTIONS OF PROSTATIC FLUID, , The clotting enzymes present in prostatic fluid convert, fibrinogen (from seminal vesicles) into coagulum. It is, essential for holding the sperms in uterine cervix., , MAINTENANCE OF SPERM MOTILITY, , LYSIS OF COAGULUM, , Prostatic fluid provides optimum pH for the motility of, sperms. Generally, sperms are nonmotile at a pH of, , The coagulum is dissolved by fibrinolysin of prostatic, fluid, so that the sperms become motile.
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Chapter 76 t Prostate Gland 469, , APPLIED PHYSIOLOGY –, ENLARGEMENT OF PROSTATE GLAND, Enlargement of prostate gland is of two types:, 1. Benign enlargement, 2. Malignant enlargement., 1. Benign enlargement, Hyperplasia of glandular structures and connective, tissues causes benign (nonmalignant) enlargement of, prostate gland. It occurs in some men after 60 years of, age, due to unknown causes., , Enlarged prostate gland stretches the urethra and, obstructs urine outflow from bladder., Common symptoms are increase in the frequency, of urination, difficulty in urination, dribbling of urine after, urination and occasional renal failure., 2. Malignant enlargement, Malignant enlargement (cancer) of prostate gland also, causes obstruction of urinary passage. In addition, the, metastasis (spread of cancer from primary site to other, places) affects the other tissues, particularly bones.
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Chapter, , Semen, , , , , , 77, , INTRODUCTION, NATURE OF SEMEN, PROPERTIES OF SEMEN, COMPOSITION OF SEMEN, , , , , SPERM, PRODUCTS FROM SEMINAL VESICLES, PRODUCTS FROM PROSTATE GLAND, , SEMEN ANALYSIS, QUALITIES OF SEMEN REQUIRED FOR FERTILITY, APPLIED PHYSIOLOGY, , INTRODUCTION, Semen is a white or grey fluid that contains sperms. It, is the collection of fluids from testes, seminal vesicles,, prostate gland and bulbourethral glands. Semen, is discharged during sexual act and the process of, discharge of semen is called ejaculation., Testes contribute sperms. Prostate secretion, gives milky appearance to the semen. Secretions from, seminal vesicles and bulbourethral glands provide, mucoid consistency to semen., , NATURE OF SEMEN, At the time of ejaculation, human semen is liquid in, nature. Immediately, it coagulates and after some time, it becomes liquid once again (secondary liquefaction)., Fibrinogen secreted from the seminal vesicle, is converted into a weak coagulum by the clotting, enzymes secreted from prostate gland. Coagulum, is liquefied after about 30 minutes, as it is lysed by, fibrinolysin produced in prostate gland., When semen is ejaculated, the sperms are nonmotile due to the viscosity of coagulum. When the, coagulum dissolves, the sperms become motile., , PROPERTIES OF SEMEN, 1. Specific gravity : 1.028, 2. Volume, : 2 mL to 6 mL per ejaculation, 3. Reaction, : It is alkaline with a pH of 7.5., Alkalinity is due to the prostate, fluid., , COMPOSITION OF SEMEN, Semen contains 10% sperms and 90% of fluid part, which, is called seminal plasma. Seminal plasma contains the, products from seminal vesicle and prostate gland (Fig., 77.1). It also has small amount of secretions from the, mucus glands, particularly the bulbourethral glands., SPERM, Sperm is the male gamete (reproductive cell), developed, in the testis. It is also called spermatozoon (plural =, spermatozoa). Matured sperm is 60 µ long., Sperm Count, Total count of sperm is about 100 to 50 million/mL of, semen. Sterility occurs when the sperm count falls, below 20 million/mL.
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Chapter 77 t Semen 471, , FIGURE 77.1: Composition of semen, , Though the sperms can be stored in male genital, tract for longer periods, after ejaculation the survival, time is only about 24 to 48 hours at a temperature, equivalent to body temperature., Rate of motility of sperm in female genital tract is, about 3 mm/minute. Sperms reach the fallopian tube, in about 30 to 60 minutes after sexual intercourse., Uterine contractions during sexual act facilitate the, movement of sperms., Structure of Sperm, Sperm consists of four parts (Fig. 77.2):, 1. Head, 2. Neck, 3. Body, 4. Tail., 1. Head, Head of sperm is oval in shape (in front view), with a, length of 3 to 5 µ and width of up to 3 µ. Anterior portion, of head is thin., Head is covered by a thin cell membrane and it is, formed by a condensed nucleus with a thin cytoplasm., Anterior two thirds of the head is called acrosome or, galea capitis., , Acrosome, Acrosome is the thick cap like anterior part of sperm, head. It develops from Golgi apparatus and it is made, up of mucopolysaccharide and acid phosphatase., Acrosome also contains hyaluronidase and proteolytic, , FIGURE 77.2: Human sperm, , enzymes, which are essential for the sperm to fertilize, the ovum., 2. Neck, Head is connected to the body by a short neck. Its, anterior end is formed by thick disk-shaped anterior end
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472 Section 7 t Reproductive System, knob, which is also called proximal centriole. Posterior, end is formed by another similar structure known as, posterior end knob. It gives rise to the axial filament, of body., Often, the neck and body of sperm are together, called midpiece., 3. Body, Body is cylindrical with a length of 5 to 9 µ and the, thickness of 1 µ. The body of the sperm consists of, a central core called axial filament, covered by thin, cytoplasmic capsule., Axial filament starts from posterior end knob of the, neck. It passes through the body and a perforated disc, called end disk or end ring centriole. Finally, the axial, filament reaches the tail as axial thread., In the body, the axial filament is surrounded, by a closely wound spiral filament consisting of, mitochondria., 4. Tail, Tail of the sperm consists of two segments:, i. Chief or main piece: It is enclosed by cytoplasmic capsule and has an axial thread. It is 40, to 50 µ long, ii. Terminal or end piece: It has only the axial, filament., , QUALITIES OF SEMEN REQUIRED, FOR FERTILITY, Minimum required qualities of semen for fertility are:, 1. Volume of semen per ejaculation must be at least, 2 mL, 2. Sperm count must be at least 20 million/mL, 3. Number of sperms in each ejaculation must be at, least 40 million, 4. 75% of sperms per ejaculation must be alive, 5. 50% of sperms must be motile, 6. 30% of sperms must have normal shape and, structure, 7. Sperms with head defect must be less than 35%, 8. Sperms with midpiece defect must be less than 20%, 9. Sperms with tail defect must be less than 20%., , APPLIED PHYSIOLOGY, Azoospermia, Azoospermia is the condition characterized by lack of, sperm in semen. It is a congenital disease. It is also, caused by excess use of corticosteroids and androgens., Oligozoospermia, Oligozoospermia is the low sperm count with less than, 20 million of sperms/mL of semen. Oligozoospermia, causes infertility., Teratozoospermia, , PRODUCTS FROM PROSTATE GLAND, , Teratozoospermia is the condition characterized by, presence of sperms with abnormal morphology. It is, also called teratospermia. It occurs in Crohn’s disease,, Hodgkin disease and celiac disease. The abnormal, morphology of sperm results in infertility., , Products of prostate gland are given in Figure 77.1., , Aspermia, , PRODUCTS FROM SEMINAL VESICLES, Products of seminal vesicles are given in Figure 77.1., , SEMEN ANALYSIS, Analysis of semen evaluates the qualities of semen,, which is useful to investigate the infertility., Parameters of semen analysis:, 1. Volume, 2. Reaction and pH, 3. Liquefaction, 4. Sperm count, 5. Morphology of sperm, 6. Motility of sperms, 7. Pus cells and RBCs, 8. Fructose level., , Aspermia is the lack of semen. It occurs due to retrograde ejaculation. Retrograde ejaculation is the, entrance of semen into urinary bladder instead of, entering urethra. It is due to dysfunction of sphincter, of the bladder, which is caused by prostatic surgery or, excess use of drugs. Aspermia leads to infertility., Oligospermia, Oligospermia is a genetic disorder characterized by low, volume of semen., Hematospermia, Hematospermia is the appearance of blood in sperm. It, occurs due to infection of urethra or prostate. It is also, common in congenital bleeding disorder.
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Female Reproductive, System, , Chapter, , 78, , FEMALE REPRODUCTIVE ORGANS, , , , , PRIMARY SEX ORGANS, ACCESSORY SEX ORGANS, FUNCTIONAL ANATOMY OF ACCESSORY SEX, ORGANS, , SEXUAL LIFE IN FEMALES, , , , , FIRST PERIOD, SECOND PERIOD, THIRD PERIOD, , FEMALE REPRODUCTIVE ORGANS, Female reproductive system comprises of primary sex, organs and accessory sex organs (Fig. 78.1)., PRIMARY SEX ORGANS, Primary sex organs are a pair of ovaries, which produce, eggs or ova and secrete female sex hormones, the, , estrogen and progesterone. Details of structure and, functions of ovary are given in Chapter 79., ACCESSORY SEX ORGANS, Accessory sex organs in females are:, 1. A system of genital ducts: Fallopian tubes, uterus,, cervix and vagina (Figs. 78.2 and 78.3), , FIGURE 78.1: Female reproductive organs and other organs of pelvis
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474 Section 7 t Reproductive System, , FIGURE 78.2: Female reproductive system, , tubes open. Uterus communicates with peritoneal, cavity through fallopian tubes., Virgin uterus is pyriform in shape and is flattened, anteroposteriorly. It measures about 7.5 cm in length,, 5 cm in breadth at its upper part and about 2.5 cm in, thickness. There is a constriction almost at the middle, of uterus called isthmus., Divisions of uterus, Uterus is divided into three portions:, 1. Fundus (above the entrance points of fallopian tubes), 2. Body (between fundus and isthmus), 3. Cervix (below isthmus)., Structure of uterus, FIGURE 78.3: Section of uterus, , 2. External genitalia: Labia majora, labia minora and, clitoris., Mammary glands are not the female genital organs, but are the important glands of female reproductive, system., FUNCTIONAL ANATOMY OF, ACCESSORY SEX ORGANS, Uterus, Uterus is otherwise known as womb. It lies in the pelvic, cavity, in between the rectum and urinary bladder., Uterus is a hollow muscular organ with a thick wall. It, has a central cavity, which opens into vagina through, cervix. On either side at its upper part, the fallopian, , Uterus is made up of three layers:, 1. Serous or outer layer, 2. Myometrium or middle muscular layer, 3. Endometrium or inner mucus layer., 1. Serous or outer layer, Serous or outer layer is the covering of uterus derived, from peritoneum. Anteriorly, it covers the uterus com, pletely, but posteriorly it covers only up to the isthmus., 2. Myometrium or middle muscular layer, Myometrium is the thickest layer of uterus and it is, made up of smooth muscle fibers., Smooth muscle fibers of myometrium are arranged, in three layers:, i. External myometrium with transversely arranged, muscle fibers
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Chapter 78 t Female Reproductive System 475, ii. Middle myometrium with muscle fibers arranged, longitudinally, obliquely and transversely, iii. Internal myometrium with circular muscle fibers., Muscular layer is interdisposed with blood vessels,, nerve fibers, lymphatic vessels and areolar tissues., , 2. Lower vaginal portion, which projects into the, anterior wall of the vagina and it communicates with, vagina through external os (orifice) of cervix. Mucus, membrane of this portion is formed by stratified, epithelial cells., , 3. Endometrium or inner mucus layer, , Vagina, , Endometrium is smooth and soft with pale red color. It is, made up of ciliated columnar epithelial cells., Surface of the endometrium has minute orifices,, through which tubular follicles of endometrium open., Endometrium also contains connective tissue in which, the uterine glands are present. Uterine glands are lined, by ciliated columnar epithelial cells., , Vagina is a short tubular organ. It is lined by mucus, membrane, which is formed by stratified epithelial cells., , Changes in uterus, Uterus changes its size, structure and function in, different phases of sexual life., Just before menstruation, uterus is enlarged,, becomes more vascular. The endometrium thickens with, more blood supply. This layer is desquamated during, menstruation and reformed after menstrual period., During pregnancy, uterus is enlarged very much, with increase in weight. After parturition (delivery), it, comes back to its original size but the cavity remains, larger. In old age, uterus is atrophied., Cervix, Cervix is the lower constricted part of uterus. It is divided, into two portions:, 1. Upper supravaginal portion, which communicates, with body of uterus through internal os (orifice), of cervix. Mucus membrane of this portion has, glandular follicles, which secrete mucus., , SEXUAL LIFE IN FEMALES, Lifespan of a female is divided into three periods., FIRST PERIOD, First period extends from birth to puberty. During this, period, primary and accessory sex organs do not, function. These organs remain quiescent. Puberty, occurs at the age of 12 to 15 years., SECOND PERIOD, Second period extends from onset of puberty to the, onset of menopause. First menstrual cycle is known as, menarche. Permanent stoppage of the menstrual cycle, in old age is called menopause, which occurs at the, age of about 45 to 50 years. During the period between, menarche and menopause, women menstruate and, reproduce., THIRD PERIOD, Third period extends after menopause to the rest of the, life.
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Chapter, , Ovary, , 79, , INTRODUCTION, FUNCTIONAL ANATOMY OF OVARY, , , , MEDULLA, CORTEX, , OVARIAN HORMONES, , , , , , ESTROGEN, FUNCTIONS OF ESTROGEN, PROGESTERONE, FUNCTIONS OF PROGESTERONE, , INTRODUCTION, Ovary is the gonad or primary sex organs in females., A woman has two ovaries. Ovaries have two functions,, gametogenic and endocrine functions. Gametogenic, function is the production and release of ovum or, egg, which is the female gamete (reproductive cell)., Endocrine function of ovaries is the secretion of female, sex hormones., , FUNCTIONAL ANATOMY OF OVARY, Ovaries are flattened ovoid bodies, with dimensions of, 4 cm in length, 2 cm in width and 1 cm in thickness., Each ovary is attached at hilum to the broad ligament,, by means of mesovarium and ovarian ligament., Each ovary has two portions:, 1. Medulla, 2. Cortex., MEDULLA, Medulla or zona vasculosa is the central deeper portion, of the ovary. It has the stroma of loose connective tissues., It contains blood vessels, lymphatics, nerve fibers and, bundles of smooth muscle fibers near the hilum., CORTEX, Cortex is the outer broader portion and has compact, cellular layers. It is interrupted at the hilum, where the, , medulla is continuous with mesovarium. Cortex is lined, by the germinal epithelium underneath a fibrous layer, known as ‘tunica albuginea’., Cortex consists of the following structures:, i. Glandular structures, which represent ovarian, follicles at different stages, ii. Connective tissue cells, iii. Interstitial cells, which are clusters of epithelial, cells with fine lipid granules formed mainly from, theca interna., Ovarian Follicles, In the intrauterine life, outer part of cortex contains, the germinal epithelium, which is derived from the, germinal ridges. When fetus develops, the germinal, epithelium gives rise to a number of primordial ova., The primordial ova move towards the inner substance, of cortex. A layer of spindle cells called granulose cells, from the ovarian stroma surround the ova. Primordial, ovum along with granulosa cells is called the primordial, follicle (Fig. 79.1)., At 7th or 8th month of intrauterine life, about 6, million primordial follicles are found in the ovary. But, at the time of birth, only 1 million primordial follicles, are seen in both the ovaries and the rest of the follicles, degenerate. At the time of puberty, the number decreases, further to about 300,000 to 400,000. After menarche,, during every menstrual cycle, one of the follicles matures
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Chapter 79 t Ovary 477, and in small quantity by corpus luteum of the ovaries., Estrogen secretion is predominant at the later stage of, follicular phase before ovulation (Chapter 80)., Estrogen is derived from androgens, particularly, androstenedione, which is secreted in theca interna, cells. Androstenedione migrates from theca cells to, granulosa cells, where it is converted into estrogen by, the activity of the enzyme aromatase., A small quantity of estrogen is also secreted by, adrenal cortex. In pregnant woman, a large amount of, estrogen is secreted by the placenta., Chemistry, Estrogen is a C18 steroid., Different Forms, , FIGURE 79.1: Ovarian follicles and corpus luteum, , and releases its ovum. During every menstrual cycle,, only one ovum is released from any one of the ovaries., During every cycle, many of the follicles degenerate., The degeneration of the follicles is called atresia and, the degenerated follicles are known as atretic follicles., The atretic follicles become fibrous and the fibrotic, follicles are called the corpus fibrosa. Atresia occurs at, all levels of follicles. Usually, the degenerated follicles, disappear without leaving any scar., Functions of Ovaries, Ovaries are the primary sex organs in females. Functions, of ovaries are:, 1. Secretion of female sex hormones, 2. Oogenesis, 3. Menstrual cycle., Sex hormones are discussed in this Chapter., Oogenesis and menstrual cycle are explained in the, next Chapter., , OVARIAN HORMONES, Ovary secretes the female sex hormones estrogen, and progesterone. Ovary also secretes few more, hormones, namely inhibin (Chapter 80), relaxin, (Chapter 84) and small quantities of androgens., ESTROGEN, Source of Secretion, In a normal non-pregnant woman, estrogen is secreted, in large quantity by theca interna cells of ovarian follicles, , Estrogen is present in three forms in plasma:, 1. β-estradiol, 2. Estrone, 3. Estriol., All the three forms of estrogen are present in, significant quantities in plasma. The quantity and, potency of β-estradiol are more than those of estrone, and estriol., Plasma Level, Plasma level of estrogen in females at normal, reproductive age varies during different phases of, menstrual cycle. In follicular phase, it is 30 to 200 pg/mL, (Fig. 80.4). In normal adult male, estrogen level is 12 to, 34 pg/mL., Half-life, Half-life of estrogen is 30 to 60 minutes., Synthesis, The different forms of estrogen are synthesized from, the cholesterol or acetate. If estrogen is formed from, acetate, first acetate is converted into cholesterol., Pathway for synthesis of estrogen, Acetate → Cholesterol → Pregnenolone, , ↓, , Estrogen ← Testosterone ← Progesterone, During synthesis of estrogen, progesterone and, testosterone are synthesized first (Fig. 70.2). Then,, before leaving the ovaries, almost all the testosterone, and much of the progesterone are converted into, estrogen. About 1/15 of testosterone is secreted into, the plasma of the female by the ovaries.
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478 Section 7 t Reproductive System, Transport in Plasma, , 3. Effect on Fallopian Tubes, , Estrogen is transported mainly by the plasma protein,, albumin. A small quantity of estrogen is also transported, by globulin. The binding of estrogen with the plasma, protein is loose, so that the hormones are released into, the tissues easily., , Estrogen:, i. Acts on the mucosal lining of the fallopian, tubes and increases the number and size of the, epithelial cells, especially the ciliated epithelial, cells lining the fallopian tubes, ii. Increases the activity of the cilia, so that the, movement of ovum in the fallopian tube is, facilitated, iii. Enhances the proliferation of glandular tissues, in fallopian tubes., All these changes are necessary for the fertilization, of ovum., , Metabolism, Estrogen is degraded mainly in the liver. Here, it is, conjugated with glucuronides and sulfates. About one, fifth of the conjugated products are excreted in the bile., Most of the remaining part is excreted in the urine. Liver, also converts the potent active beta estradiol into the, almost inactive estrogen, the estriol., FUNCTIONS OF ESTROGEN, Major function of estrogen is to promote cellular, proliferation and tissue growth in the sexual organs and, in other tissues, related to reproduction. In childhood, the, estrogen is secreted in small quantity. During puberty,, the secretion increases sharply, resulting in changes in, the sexual organs. Effects of estrogen are:, 1. Effect on Ovarian Follicles, Estrogen promotes the growth of ovarian follicles by, increasing the proliferation of the follicular cells. It also, increases the secretory activity of theca cells (Refer, Chapter 80 for details)., , 4. Effect on Vagina, Estrogen:, i. Changes the vaginal epithelium from cuboidal, into stratified type; the stratified epithelium is, more resistant to trauma and infection, ii. Increases the layers of the vaginal epithelium by, proliferation, iii. Reduces the pH of vagina, making it more, acidic., All these changes are necessary for the prevention, of certain common vaginal infections such as gonorrheal, vaginitis. Such infections can be cured by the administration of estrogen., 5. Effect on Secondary Sexual Characters, Estrogen is responsible for the development of secondary, sexual characters (Chapter 74) in females., , 2. Effect on Uterus, , Secondary sexual characters in female, , Estrogen produces the following changes in uterus:, i. Enlargement of uterus to about double of, its childhood size due to the proliferation of, endometrial cells, ii. Increase in the blood supply to endometrium, iii. Deposition of glycogen and fats in endometrium, iv. Proliferation and dilatation of blood vessels of, endometrium, v. Proliferation and dilatation of the endometrial, glands, which become more tortuous with, increased blood flow, vi. Increase in the spontaneous activity of the, uterine muscles and their sensitivity to oxytocin, vii. Increase in the contractility of the uterine, muscles., All these changes prepare uterus for pregnancy., , i. Hair distribution: Hair develops in the pubic, region and axilla. In females, pubic hair has the, base of the triangle upwards. Body hair growth, is less. Scalp hair grows profusely, ii. Skin: Skin becomes soft and smooth. Vascularity, of skin also increases, iii. Body shape: Shoulders become narrow, hip, broadens, thighs converge and the arms, diverge. Fat deposition increases in breasts and, buttocks, iv. Pelvis:, a. Broadening of pelvis with increased, transverse diameter, b. Round or oval shape of pelvis, c. Round or oval=shaped pelvic outlet., Thus, pelvis in females is different from that of, males, which is funnel shaped.
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Chapter 79 t Ovary 479, iv. Voice: Larynx remains in prepubertal stage,, which produces high-pitch voice., , uterus, liver, heart and kidneys. The β estrogen receptors, are present in ovaries and other tissues., Estrogen acts through genes., , 6. Effect on Breast, Estrogen causes:, i. Development of stromal tissues of breasts, ii. Growth of an extensive ductile system, iii. Deposition of fat in the ductile system., All these effects prepare the breasts for lactation., Estrogen causes development of lobules and alveoli, of the breasts, to some extent. However, progesterone, is necessary for the full growth of breast and prolactin, is necessary for its function., 7. Effect on Bones, Estrogen increases osteoblastic activity. So, at the, time of puberty, the growth rate increases enormously., But, at the same time, estrogen causes early fusion of, the epiphysis with the shaft. This effect is much stronger, in females than the similar effect of testosterone in, males. As a result, the growth of the females usually, ceases few years earlier than in the males., In old age, the estrogen is not secreted or it, becomes scanty. It leads to osteoporosis, in which the, bones become extremely weak and fragile. Because, of this, the bones are highly susceptible for fractures, (Chapter 68)., 8. Effect on Metabolism, , Regulation of Estrogen Secretion, Estrogen secretion is regulated by follicle-stimulating, hormone (FSH) released from anterior pituitary. Release, of FSH is stimulated by the gonadotropin-releasing, hormone (GnRH) secreted from hypothalamus., Theca cells and granulosa cells have many FSH, receptors. After binding with the receptors, FSH acts via, cAMP and stimulates the secretory activities of theca, and granulosa cells. Estrogen inhibits secretion of FSH, and GnRH by negative feedback. Inhibin secreted by, granulosa cells (Chapter 80) also decreases estrogen, secretion, by inhibiting the secretion of FSH and GnRH, (Fig. 79.2)., PROGESTERONE, Source of Secretion, In non-pregnant woman, a small quantity of progesterone, is secreted by theca interna cells of ovaries during the, first half of menstrual cycle, i.e. during follicular stage., But, a large quantity of progesterone is secreted during, the latter half of each menstrual cycle, i.e. during, secretory phase by the corpus luteum. Small amount of, progesterone is secreted from adrenal cortex also., In pregnant woman, large amount of progesterone is, secreted by the corpus luteum in the first trimester. In the, second trimester, corpus luteum degenerates. Placenta, , i. On protein metabolism, Estrogen induces anabolism of proteins, by which it, increases the total body protein., ii. On fat metabolism, Estrogen causes deposition of fat in the subcutaneous, tissues, breasts, buttocks and thighs. The overall specific, gravity of the female body is considerably lesser than, that of males because of fat deposition., 9. Effect on Electrolyte Balance, Estrogen causes sodium and water retention from the, renal tubules. This effect is normally insignificant but, in pregnancy, it becomes more significant., Mode of Action of Estrogen, Estrogen receptors situated on nuclear membrane of, target cells are of two types namely α and β estrogen, receptors. The α-estrogen receptors are present in, , FIGURE 79.2: Regulation of estrogen secretion., Red dotted lines indicate inhibition.
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480 Section 7 t Reproductive System, secretes large quantity of progesterone in second and, third trimesters., Chemistry, Progesterone is a C21 steroid., Half-life, Half-life of progesterone is 4 to 5 minutes., Synthesis, Progesterone is synthesized from acetate or cholesterol in, the ovaries, along with estrogen (Fig. 70.2, Chapter 70)., Plasma Level, Plasma level of progesterone in females at normal, reproductive age varies during different phases of, menstrual cycle. In follicular phase, it is about 0.9 ng/mL, (Fig. 80.4). In normal adult male, progesterone level is, 0.3 ng/mL., Transport in Blood, Like estrogen, progesterone is also transported in the, blood by the plasma proteins – albumin and globulin., , Progesterone:, i. Increases the thickness of the endometrium by, increasing the number and size of the cells, Thickness of endometrium increases from 1 mm, thickness at the beginning of secretory phase to, about 5 to 6 mm at the end of secretory phase., ii. Increases the size of uterine glands and these, glands become more tortuous, iii. Increases the secretory activities of epithelial, cells of uterine glands, iv. Increases the deposition of lipid and glycogen in, the stromal cells of endometrium, v. Increases the blood supply to endometrium., It is due to increase in size of the vessels and, vasodilatation, vi. Decreases the frequency of uterine contractions, during pregnancy. Because of this, the expulsion, of the implanted ovum is prevented., 3. Effect on Cervix, Progesterone increases the thickness of cervical, mucosa and thereby inhibits the transport of sperm, into uterus. This effect is utilized in the contraceptive, actions of minipills., 4. Effect on the Mammary Glands, , Metabolism, Within few minutes after secretion, almost all the, progesterone is degraded into other steroids, which, do not have progesterone effect. The degradation, occurs in liver. The main end product of progesterone, degradation is pregnanediol, which is conjugated with, glucuronic acid and excreted in the urine., , Progesterone promotes the development of lobules, and alveoli of mammary glands by proliferating and, enlarging the alveolar cells. It also makes the breasts, secretory in nature. It makes the breasts to swell by, increasing the secretory activity and fluid accumulation, in the subcutaneous tissue., 5. Effect on Hypothalamus, , FUNCTIONS OF PROGESTERONE, Progesterone is concerned mainly with the final, preparation of the uterus for pregnancy and the breasts, for lactation. The effects of progesterone are:, , Progesterone inhibits the release of LH from hypothalamus through feedback effect. This effect is utilized, for its contraceptive action., 6. Thermogenic Effect, , 1. Effect on Fallopian Tubes, Progesterone promotes the secretory activities of, mucosal lining of the fallopian tubes. Secretions of, fallopian tubes are necessary for nutrition of the fertilized, ovum, while it is in fallopian tube before implantation., , Progesterone increases the body temperature after, ovulation. The mechanism of thermogenic action is not, known. It is suggested that progesterone increases the, body temperature by acting on hypothalamic centers, for temperature regulation., , 2. Effect on the Uterus, , 7. Effect on Respiration, , Progesterone promotes the secretory activities of, uterine endometrium during the secretory phase of, the menstrual cycle. Thus, the uterus is prepared for, implantation of the fertilized ovum., , During luteal phase of menstrual cycle and during, pregnancy, progesterone increases the ventilation via, respiratory center. This decreases the partial pressure, of carbon dioxide in the alveoli.
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Chapter 79 t Ovary 481, 8. Effect on Electrolyte Balance, Progesterone increases the reabsorption of sodium and, water from the renal tubules. However, in large doses,, it is believed to cause excretion of sodium and water., This may be due to an indirect effect, i.e. progesterone, combines with the same receptors, which bind with, aldosterone. So, the action of aldosterone is blocked,, leading to the excretion of sodium and water., Mode of Action of Progesterone, The progesterone receptors situated on the nuclear, membrane of target cells are of two types, namely, , A-progesterone receptors and B-progesterone receptors. Exact location of each type of progesterone, receptor is not clear., Like estrogen, progesterone also acts through, genes., Regulation of Progesterone Secretion, LH from anterior pituitary activates the corpus luteum, to secrete progesterone. Secretion of LH is influenced, by the gonadotropin-releasing hormone secreted in, hypothalamus. Progesterone inhibits the release of LH, from anterior pituitary by negative feedback.
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Chapter, , Menstrual Cycle, , 80, , INTRODUCTION, , , , , DEFINITION, DURATION OF MENSTRUAL CYCLE, CHANGES DURING MENSTRUAL CYCLE, , OVARIAN CHANGES DURING MENSTRUAL CYCLE, , , , , FOLLICULAR PHASE, OVULATION, LUTEAL PHASE, , UTERINE CHANGES DURING MENSTRUAL CYCLE, , , , , MENSTRUAL PHASE, PROLIFERATIVE PHASE, SECRETORY PHASE, , CHANGES IN CERVIX AND VAGINA DURING MENSTRUAL CYCLE, , , , CHANGES IN CERVIX DURING MENSTRUAL CYCLE, VAGINAL CHANGES DURING MENSTRUAL CYCLE, , REGULATION OF MENSTRUAL CYCLE, , , , , HORMONES INVOLVED IN REGULATION, REGULATION OF OVARIAN CHANGES, REGULATION OF UTERINE CHANGES, , APPLIED PHYSIOLOGY – ABNORMAL MENSTRUATION, , , , , , MENSTRUAL SYMPTOMS, PREMENSTRUAL SYNDROME, ABNORMAL MENSTRUATION, ANOVULATORY CYCLE, , INTRODUCTION, DEFINITION, Menstrual cycle is defined as cyclic events that take, place in a rhythmic fashion during the reproductive period, of a woman’s life. Menstrual cycle starts at the age of, 12 to 15 years, which marks the onset of puberty. The, commencement of menstrual cycle is called menarche., Menstrual cycle ceases at the age of 45 to 50 years., Permanent cessation of menstrual cycle in old age is, called menopause., , DURATION OF MENSTRUAL CYCLE, Duration of menstrual cycle is usually 28 days. But,, under physiological conditions, it may vary between, 20 and 40 days., CHANGES DURING MENSTRUAL CYCLE, During each menstrual cycle, series of changes occur in, ovary and accessory sex organs., These changes are divided into 4 groups:, 1. Ovarian changes, 2. Uterine changes
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Chapter 80 t Menstrual Cycle 483, 3. Vaginal changes, 4. Changes in cervix., All these changes take place simultaneously., , OVARIAN CHANGES DURING, MENSTRUAL CYCLE, Changes in the ovary during each menstrual cycle occur, in two phases:, A. Follicular phase, B. Luteal phase., Ovulation occurs in between these two phases., FOLLICULAR PHASE, Follicular phase extends from the 5th day of the cycle, until the time of ovulation, which takes place on 14th, day. Maturation of ovum with development of ovarian, follicles takes place during this phase., Ovarian Follicles, Ovarian follicles are glandular structures present in, the cortex of ovary. Each follicle consists of the ovum, surrounded by epithelial cells, namely granulosa cells., The follicles gradually grow into a matured follicle, through various stages., Different follicles:, 1., 2., 3., 4., , Primordial follicle, Primary follicle, Vesicular follicle, Matured follicle or graafian follicle., , 1. Primordial Follicle, At the time of puberty, both the ovaries contain about, 400,000 primordial follicles. Diameter of the primordial, follicle is about 15 to 20 µ and that of ovum is about 10 µ., Each primordial follicle has an ovum, which is, incompletely surrounded by the granulosa cells (Chapter, 79, Fig. 79.1). These cells provide nutrition to the ovum, during childhood., Granulosa cells also secrete the oocyte maturation, inhibiting factor, which keeps ovum in the immature, stage. All the ova present in the ovaries are formed, before birth. No new ovum is developed after birth., At the onset of puberty, under the influence of FSH, and LH the primordial follicles start growing through, various stages., 2. Primary Follicle, Primordial follicle becomes the primary follicle, when, ovum is completely surrounded by the granulosa cells., , During this stage, the follicle and the ovum increase in, size. Diameter of the follicle increases to 30 to 40 µ and, that of ovum increases to about 20 µ. The follicle is not, covered by a definite connective tissue capsule., Changes taking place during development, of primary follicle, i. Proliferation of granulosa cells and increase in, size of the follicle, ii. Increase in size of the ovum, iii. Onset of formation of connective tissue capsule, around the follicle., Primary follicles develop into vesicular follicles., 3. Vesicular Follicle, Under the influence of FSH, about 6 to 12 primary follicles, start growing and develop into vesicular follicles., Changes taking place during the development of, vesicular follicle, i. Changes in granulosa cells, ii. Changes in ovum, iii. Formation of capsule., i. Changes in granulosa cells, a. First, the proliferation of granulosa cells occurs, b. A cavity called follicular cavity or antrum is, formed in between the granulosa cells, c. Antrum is filled with a serous fluid called the, liquor folliculi, , d. With continuous proliferation of granulosa cells,, the follicle increases in size, e. Antrum with its fluid also increases in size, f. Ovum is pushed to one side and it is surrounded, by granulosa cells, which forms the germ hill or, cumulus oophorus, , g. Granulosa cells, which line the antrum form, membrana granulosa, , h. Cells of germ hill become columnar and form, corona radiata., , ii. Changes in ovum, a. First, the ovum increases in size and its diameter, increases to 100 to 150 µ, b. Nucleus becomes larger and vesicular, c. Cytoplasm becomes granular, d. Thick membrane is formed around the ovum,, which is called zona pellucida, e. A narrow cleft appears between ovum and zona, pellucida. This cleft is called perivitelline space.
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484 Section 7 t Reproductive System, iii. Formation of capsule, Spindle cells from the stroma of ovarian cortex are, modified and form a covering sheath around the follicle., The covering sheath is known as follicular sheath or, theca folliculi., , Theca folliculi divides into two layers:, a. Theca interna, b. Theca externa., , a. Theca interna, Theca interna is the inner vascular layer with loose, connective tissue. This layer also contains special type, of epithelial cells with lipid granules and some delicate, collagen fibers., Epithelial cells become secretory in nature and start, secreting the female sex hormones, especially estrogen., Hormones are released into the fluid of antrum., b. Theca externa, Theca externa is the outer layer of follicular capsule, and consists of thickly packed fibers and spindleshaped cells., After about 7th day of menstrual cycle, one of the, vesicular follicles outgrows others and becomes the, dominant follicle. It develops further to form graafian, follicle. Other vesicular follicles degenerate and become, atretic by means of apoptosis., 4. Graafian Follicle, Graafian follicle is the matured ovarian follicle with, maturing ovum (Fig. 80.1). It is named after the Dutch, physician and anatomist, Regnier De Graaf., Changes taking place during the development, of graafian follicle, i. Size of the follicle increases to about 10 to 12, mm. It extends through the whole thickness of, ovarian cortex, ii. At one point, the follicle encroaches upon tunica, albuginea and protrudes upon surface of the, ovary. This protrusion is called stigma. At the, stigma, the tunica albuginea becomes thin, iii. Follicular cavity becomes larger and distended, with fluid, iv. Ovum attains maximum size, v. Zona pellucida becomes thick, vi. Corona radiata becomes prominent, vii. Small spaces filled with fluid appear between, the cells of germ hill, outside the corona radiata., These spaces weaken the attachment of the, ovum to the follicular wall, viii. Theca interna becomes prominent. Its thickness, becomes double with the formation of rich, capillary network, , FIGURE 80.1: Graafian follicle, , ix. On the 14th day of menstrual cycle, graafian, follicle is ready for the process of ovulation., OVULATION, Ovulation is the process by which the graafian follicle, ruptures with consequent discharge of ovum into the, abdominal cavity. It is influenced by LH. Ovulation, occurs on 14th day of menstrual cycle in a normal cycle, of 28 days. The ovum enters the fallopian tube., Process of Ovulation, Mechanism of ovulation is not known clearly. Process, of ovulation is explained in the next Chapter., Stages of ovulation, 1. Rupture of graafian follicles takes place at the, stigma, 2. Follicular fluid oozes out, 3. Germ hillock is freed from wall, 4. Ovum is expelled out into the abdominal cavity along, with some amount of fluid and granulosa cells, 5. From abdominal cavity, the ovum enters the fallopian, tube through the fimbriated end., Other details are given in the next Chapter., Ovum becomes haploid before or during ovulation, by the formation of polar bodies. After ovulation, the, ovum is viable only for 24 to 48 hours. So it must be, fertilized within that time., Fertilized ovum is called zygote. Zygote moves, from fallopian tube and reaches the uterus on 3rd day, after ovulation. It is implanted in the uterine wall on 6th, or 7th day.
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Chapter 80 t Menstrual Cycle 485, If fertilization does not occur, ovum degenerates., Generally, only one ovum is released from one of the, ovaries., , fluid containing fibrin. Corpus luteum obtains a diameter, of 15 mm and remains in the ovary till the end of the, cycle., , LUTEAL PHASE, , Structure of Corpus Luteum, , Luteal phase extends between 15th and 28th day of, menstrual cycle. During this phase, corpus luteum is, developed and hence this phase is called luteal phase, (Fig. 80.2)., , In the corpus luteum, granulosa cells and theca interna, cells are transformed into lutein cells called granulosa, , Corpus Luteum, Corpus luteum is a glandular yellow body, developed, from the ruptured graafian follicle after the release of, ovum. It is also called yellow body., Development of Corpus Luteum, Soon after the rupture of graafian follicle and release, of ovum, the follicle is filled with blood. Now the follicle, is called corpus hemorrhagicum. The blood clots, slowly. Corpus hemorrhagicum does not degenerate, immediately. It is transformed into corpus luteum., Follicular cavity closes gradually by the healing of, the wound. Blood clot is gradually replaced by a serous, , lutein cells and theca lutein cells. The process which, transforms the granulosa and theca cells into lutein cells, is called luteinization., Granulosa lutein cells contain fine lipid granules and, the yellowish pigment granules. The yellowish pigment, granules give the characteristic yellow color to corpus, luteum., Theca lutein cells contain only lipid granules and, not the yellow pigment., Follicular cavity is greatly reduced with irregular, outline. It is filled with the serous fluid and remnants of, blood clots., Functions of Corpus Luteum, 1. Secretion of hormones, Corpus luteum acts as a temporary endocrine gland., It secretes large quantity of progesterone and small, amount of estrogen. Granulosa lutein cells secrete, progesterone and theca lutein cells secrete estrogen., LH influences the secretion of these two hormones., 2. Maintenance of pregnancy, If pregnancy occurs, corpus luteum remains active for, about 3 months, i.e. until placenta develops. Hormones, secreted by corpus luteum during this period maintain, the pregnancy., Abortion occurs if corpus luteum becomes inactive, or removed before third month of pregnancy, i.e. before, placenta starts secreting the hormones., Fate of Corpus Luteum, Fate of corpus luteum depends upon whether ovum is, fertilized or not., 1. If the ovum is not fertilized, , FIGURE 80.2: Ovarian follicle, , If fertilization does not take place, the corpus luteum, reaches the maximum size about one week after, ovulation. During this period, it secretes large quantity, of progesterone with small quantity of estrogen. Then,, it degenerates into the corpus luteum menstrualis or, spurium. The cells decrease in size and the corpus, luteum becomes smaller and involuted. Afterwards,, the corpus luteum menstrualis is transformed into a
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486 Section 7 t Reproductive System, whitish scar called corpus albicans. The process by, which corpus luteum undergoes regression is called, luteolysis., , 2. If ovum is fertilized, If ovum is fertilized and pregnancy occurs, the corpus, luteum persists and increases in size. It attains a, diameter of 20 to 30 mm and it is transformed into, corpus luteum graviditatis (verum) or corpus luteum, of pregnancy. It remains in the ovary for 3 to 4, months. During this period, it secretes large amount of, progesterone with small quantity of estrogen, which are, essential for the maintenance of pregnancy. After 3 to 4, months, placenta starts secreting these hormones and, corpus luteum degenerates., , UTERINE CHANGES DURING, MENSTRUAL CYCLE, During each menstrual cycle, along with ovarian changes,, uterine changes also occur simultaneously (Fig. 80.3)., Uterine changes occur in three phases:, 1. Menstrual phase, 2. Proliferative phase, 3. Secretory phase., MENSTRUAL PHASE, After ovulation, if pregnancy does not occur, the, thickened endometrium is shed or desquamated. This, desquamated endometrium is expelled out through, vagina along with blood and tissue fluid. The process, of shedding and exit of uterine lining along with blood, and fluid is called menstruation or menstrual bleeding., It lasts for about 4 to 5 days. This period is called, , menstrual phase or menstrual period. It is also called, menses, emmenia or catamenia., The day when bleeding starts is considered as the, first day of the menstrual cycle., Two days before the onset of bleeding, that is on, 26th or 27th day of the previous cycle, there is a sudden, reduction in the release of estrogen and progesterone, from ovary. Decreased level of these two hormones is, responsible for menstruation., Changes in Endometrium during, Menstrual Phase, i. Lack of estrogen and progesterone causes sudden, involution of endometrium, ii. It leads to reduction in the thickness of endometrium,, up to 65% of original thickness, iii. During the next 24 hours, the tortuous blood vessels, in the endometrium undergo severe constriction., Endometrial vasoconstriction is because of three, reasons:, a. Involution of endometrium, b. Actions of vasoconstrictor substances like prostaglandin, released from tissues of involuted, endometrium, c. Sudden lack of estrogen and progesterone, (which are vasodilators), iv. Vasoconstriction leads to hypoxia, which results in, necrosis of the endometrium, v. Necrosis causes rupture of blood vessels and, oozing of blood, vi. Outer layer of the necrotic endometrium is, separated and passes out along with blood, vii. This process is continued for about 24 to 36 hours, , FIGURE 80.3: Uterine changes during menstrual cycle
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Chapter 80 t Menstrual Cycle 487, viii. Within 48 hours after the reduction in the secretion, of estrogen and progesterone, the superficial layers, of endometrium are completely desquamated, ix. Desquamated tissues and the blood in the, endometrial cavity initiate the contraction of uterus, x. Uterine contractions expel the blood along with, desquamated uterine tissues to the exterior through, vagina., During normal menstruation, about 35 mL of blood, along with 35 mL of serous fluid is expelled. The, blood clots as soon as it oozes into the uterine cavity., Fibrinolysin causes lysis of clot in uterine cavity itself,, so that the expelled menstrual fluid does not clot., However, in the pathological conditions involving uterus,, the lysis of blood clot does not occur. So the menstrual, fluid comes out with blood clot., Menstruation stops between 3rd and 7th day of, menstrual cycle. At the end of menstrual phase, the, thickness of endometrium is only about 1 mm. This is, followed by proliferative phase., PROLIFERATIVE PHASE, Proliferative phase extends usually from 5th to 14th day, of menstruation, i.e. between the day when menstruation, stops and the day of ovulation. It corresponds to the, follicular phase of ovarian cycle., At the end of menstrual phase, only a thin layer, (1 mm) of endometrium remains, as most of the endometrial stroma is desquamated., Changes in Endometrium during, Proliferative Phase, i. Endometrial cells proliferate rapidly, ii. Epithelium reappears on the surface of endometrium, within the first 4 to 7 days, iii. Uterine glands start developing within the, endometrial stroma, iv. Blood vessels appear in the stroma, v. Proliferation of endometrial cells occurs continuously,, so that the endometrium reaches the thickness of 3, to 4 mm at the end of proliferative phase., All these uterine changes during proliferative phase, occur because of the influence of estrogen released, from ovary. On 14th day, ovulation occurs under the, influence of LH. This is followed by secretory phase., , After ovulation, corpus luteum is developed in, the ovary. It secretes a large quantity of progesterone, along with a small amount of estrogen. Estrogen, causes further proliferation of cells in uterus, so that, the endometrium becomes more thick. Progesterone, causes further enlargement of endometrial stroma and, further growth of glands., Under the influence of progesterone, the endometrial, glands commence their secretory function. Many, changes occur in the endometrium before commencing, the secretory function., Changes in Endometrium during, Secretory Phase, i. Endometrial glands become more tortuous. Because, of increase in size, the glands become tortuous to, get accommodated within the endometrium, ii. Cytoplasm of stromal cells increases because of, the deposition of glycogen and lipids, iii. Many new blood vessels appear within endometrial, stroma. Blood vessels also become tortuous, iv. Blood supply to endometrium increases, v. Thickness of endometrium increases up to 6 mm., Actually, secretory phase is the preparatory period,, during which the uterus is prepared for implantation of, ovum. All these uterine changes during secretory phase, occur due to the influence of estrogen and progesterone., Estrogen is responsible for repair of damaged, endometrium and growth of the glands. Progesterone, is responsible for further growth of these structures and, secretory activities in the endometrium., If a fertilized ovum is implanted during this phase, and if the implanted ovum starts developing into a, fetus, then further changes occur in the uterus for the, survival of the developing fetus. If the implanted ovum is, unfertilized or if pregnancy does not occur, menstruation, occurs after this phase and a new cycle begins., , CHANGES IN CERVIX AND VAGINA, DURING MENSTRUAL CYCLE, CHANGES IN CERVIX DURING, MENSTRUAL CYCLE, Mucus membrane of the cervix also shows cyclic, changes during different phases of menstrual cycle., Proliferative Phase, , SECRETORY PHASE, Secretory phase extends between 15th and 28th day of, the menstrual cycle, i.e. between the day of ovulation and, the day when menstruation of next cycle commences., , During proliferative phase, the mucus membrane of, cervix becomes thinner and more alkaline due to the, influence of estrogen. It helps in the survival and motility, of spermatozoa.
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488 Section 7 t Reproductive System, Secretory Phase, During secretory phase, the mucus membrane of cervix, becomes more thick and adhesive because of actions, of progesterone., VAGINAL CHANGES DURING, MENSTRUAL CYCLE, Proliferative Phase, Epithelial cells of vagina are cornified. Estrogen is, responsible for this., Secretory Phase, Vaginal epithelium proliferates due to the actions of, progesterone. It is also infiltrated with leukocytes., These two changes increase the resistance of vagina, for infection., , REGULATION OF MENSTRUAL CYCLE, Regulation of menstrual cycle is a complex process that, is carried out by a well organized regulatory system., The regulatory system is a highly integrated system,, which includes hypothalamus, anterior pituitary and, ovary with its growing follicle. In the whole scenario,, the growing follicle has a vital role to play., HORMONES INVOLVED IN REGULATION, The regulatory system functions through the hormones, of hypothalamo-pituitary-ovarian axis., Hormones involved in the regulation of menstrual, cycle are:, 1. Hypothalamic hormone: GnRH, 2. Anterior pituitary hormones: FSH and LH, 3. Ovarian hormones: Estrogen and progesterone., Hormonal level during menstrual cycle is shown in, Fig. 80.4., Hypothalamic Hormone – GnRH, GnRH triggers the cyclic changes during menstrual cycle, by stimulating secretion of FSH and LH from anterior, pituitary. GnRH secretion depends upon two factors:, i. External factors like psychosocial events, which act, on hypothalamus via cortex and many other brain, centers, ii. Feedback effects of ovarian changes via ovarian, hormones., Anterior Pituitary Hormones – FSH and LH, FSH and LH modulate the ovarian and uterine, changes by acting directly and/or indirectly via ovarian, , hormones. FSH stimulates the recruitment and growth, of immature ovarian follicles. LH triggers ovulation and, sustains corpus luteum., Secretion of FSH and LH is under the influence of, GnRH., Ovarian Hormones – Estrogen and Progesterone, Estrogen and progesterone which are secreted by, follicle and corpus luteum, show many activities during, menstrual cycle. Ovarian follicle secretes large quantity, of estrogen and corpus luteum secretes large quantity, of progesterone., Estrogen secretion reaches the peak twice in each, cycle; once during follicular phase just before ovulation, and another one during luteal phase (Fig. 80.4). On, the other hand, progesterone is virtually absent during, follicular phase till prior to ovulation. But it plays a critical, role during luteal phase., Estrogen is responsible for the growth of follicles., Both the steroids act together to produce the changes, in uterus, cervix and vagina., Both the ovarian hormones are under the influence, of GnRH, which acts via FSH and LH. In addition, the, secretion of GnRH, FSH and LH is regulated by ovarian, hormones., REGULATION OF OVARIAN CHANGES, Follicular Phase, 1. The biological clock responsible to trigger the cyclic, events is the pulsatile secretion of GnRH, at about, every 2 hours (due to some mechanism that is not, understood clearly), 2. Pulsatile release of GnRH stimulates the secretion, of FSH and LH from anterior pituitary, 3. LH induces the synthesis of androgens from theca, cells of growing follicle, 4. FSH promotes aromatase activity in granulosa, cells of the follicle (Chapter 79), resulting in the, conversion of androgens into estrogen. It also, promotes follicular development, 5. Estrogen is responsible for development and growth, of graafian follicle. It also stimulates the secretory, activities of theca cells, 6. Estrogen also exerts a double feedback control on, GnRH, i. Initially, when estrogen secretion is moderate, it, exerts a negative feedback control on GnRH so, that GnRH secretion is inhibited. This leads to, decrease in secretion of FSH and LH (negative, feedback), ii. During later period of follicular phase, when a, large amount of estrogen is secreted by the
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Chapter 80 t Menstrual Cycle 489, , FIGURE 80.4: Hormonal level during menstrual cycle. LH = Luteinizing hormones, FSH = Follicle-stimulating hormone., , maturing follicle, it exerts a positive feedback, effect on GnRH secretion. Now, GnRH secretion, is increased, resulting in secretion of large, quantity of FSH and LH. This in turn, facilitates, the growth of graafian follicle, 7. In addition, estrogen shows the following actions:, i. Increases the number of FSH and LH receptors, on the granulosa cells of follicles and increases, the sensitivity of these cells for FSH and LH, ii. Facilitates the faster growth of graafian follicle, 8. LH is necessary to provide the final touches for the, growth of graafian follicle. It stimulates the secretion, of estrogen. At the same time, it stimulates the theca, cells to secrete progesterone., , Ovulation, LH is important for ovulation. Without LH, ovulation does, not occur even with a large quantity of FSH. The need, for excessive secretion of LH for ovulation is known as, ovulatory surge for LH or luteal surge., Prior to ovulation, a large quantity of LH is secreted, due to positive feedback effect of estrogen on GnRH,, as mentioned above., Luteal Phase, Role of LH, Ovarian changes during luteal phase depend mainly on, LH.
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490 Section 7 t Reproductive System, Luteinizing hormone:, 1. Induces development of corpus luteum from the, follicle (devoid of ovum) by converting the granulosa, cells into lutein cells, 2. Stimulates corpus luteum to secrete progesterone, and estrogen, 3. Necessary for the maintenance of corpus luteum., Role of FSH, FSH also plays a role during luteal phase., Follicle-stimulating hormone:, 1. Maintains the secretory activity of corpus luteum, 2. Stimulates lutein cells to secrete inhibin, which in, turn inhibits FSH secretion., If the ovum is not fertilized or if implantation of, ovum does not take place, the changes in the level of, the hormones produce some effects on corpus luteum, which are:, 1. Progesterone and estrogen secreted from corpus, luteum, inhibit the secretion of FSH and LH from, anterior pituitary by negative feedback, 2. Granulosa lutein cells secrete another hormone, called inhibin (which is also secreted by Sertoli cells, of testes in males: Chapter 74). Inhibin also inhibits, the secretion of FSH and LH by negative feedback, 3. In the absence of FSH and LH, the corpus luteum, becomes inactive, 4. Finally, the corpus luteum regresses by means of, luteolysis; so progesterone and estrogen are not, available, 5. Absence of progesterone and estrogen induces the, secretion of GnRH from hypothalamus, 6. GnRH stimulates the secretion of FSH and LH from, anterior pituitary, 7. FSH and LH stimulate the new immature follicles,, resulting in the commencement of next cycle., REGULATION OF UTERINE CHANGES, Uterine changes during menstrual cycle are influenced, by estrogen and progesterone., Proliferative Phase, During proliferative stage, the repair of the damaged, endometrium occurs mainly by estrogen., Estrogen stimulates:, 1. Proliferation of cells in endometrial stroma, 2. Development of uterine glands and appearance of, blood vessels in the endometrial stroma., , Secretory Phase, Secretory phase of uterine changes, coincides with luteal, phase of ovarian cycle. Under the influence of FSH and, LH from anterior pituitary, the corpus luteum secretes, large amount of progesterone and small amount of, estrogen. Progesterone is responsible for endometrial, changes along with estrogen during this phase., Progesterone stimulates:, 1. Growth of endometrial glands and makes them, more tortuous, 2. Growth of blood vessels and makes them also, tortuous, leading to increase in blood flow to, endometrium, 3. Secretory activities of endometrial glands., Thus, during the secretory phase, the structure,, blood flow and secretory functions of uterus are, influenced by estrogen and progesterone secreted by, corpus luteum., Menstrual Phase, If pregnancy does not occur, menstrual phase occurs:, 1. During the last two days of secretory phase, i.e. two, days prior to onset of menstruation, the secretion of, large quantity of progesterone and estrogen from, corpus luteum inhibits the secretion of FSH and LH, from anterior pituitary, by negative feedback, 2. In the absence of LH and FSH, the corpus luteum, becomes inactive and starts regressing, 3. Sudden withdrawal (absence) of ovarian hormones, progesterone and estrogen occurs, 4. It leads to menstrual bleeding., Lack of ovarian hormones causes the release of, gonadotropins once again from anterior pituitary. It, results in the onset of development of new follicles in, ovary and the cycle repeats., , APPLIED PHYSIOLOGY –, ABNORMAL MENSTRUATION, MENSTRUAL SYMPTOMS, Menstrual symptoms are the unpleasant symptoms, with discomfort, which appear in many women during, menstruation. These symptoms are due to hormonal, withdrawal, leading to cramps in uterine muscle before, or during menstruation., Common Menstrual Symptoms, 1. Abdominal pain, 2. Dysmenorrhea (menstrual pain), 3. Headache
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Chapter 80 t Menstrual Cycle 491, 4., 5., 6., 7., , Occasional nausea and vomiting, Irritability, Depression, Migraine (neurological disorder, characterized by, intense headache causing disability)., , PREMENSTRUAL SYNDROME, Premenstrual syndrome (PMS) is the symptom of stress, that appears before the onset of menstruation. It is also, called premenstrual stress syndrome, premenstrual, stress or premenstrual tension. It lasts for about 4 to, 5 days prior to menstruation. Symptoms appear due to, salt and water retention caused by estrogen., Common Features, 1., 2., 3., 4., 5., 6., 7., 8., 9., , Mood swings, Anxiety, Irritability, Emotional instability, Headache, Depression, Constipation, Abdominal cramping, Bloating (abdominal swelling)., , ABNORMAL MENSTRUATION, 1. Amenorrhea: Absence of menstruation, 2. Hypomenorrhea: Decreased menstrual bleeding, , 3. Menorrhagia: Excess menstrual bleeding, 4. Oligomenorrhea: Decreased frequency of menstrual, bleeding, 5. Polymenorrhea:, Increased, frequency, of, menstruation, 6. Dysmenorrhea: Menstruation with pain, 7. Metrorrhagia: Uterine bleeding in between, menstruations., ANOVULATORY CYCLE, Anovulatory cycle is the menstrual cycle in which, ovulation does not occur. The menstrual bleeding occurs, but the release of ovum does not occur. It is common, during puberty and few years before menopause. When, it occurs before menopause, it is called perimenopause., If it occurs very often during childbearing years, it leads, to infertility., Common Causes, 1., 2., 3., 4., 5., 6., , Hormonal imbalance, Prolonged strenuous exercise program, Eating disorders, Hypothalamic dysfunctions, Tumors in pituitary gland, ovary or adrenal gland, Long-term use of drugs like steroidal oral, contraceptives.
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Chapter, , Ovulation, , , , , , 81, , INTRODUCTION, PROCESS OF OVULATION, HORMONAL REGULATION OF OVULATION, DETERMINATION OF OVULATION TIME, , , , , , , DETERMINATION OF BASAL BODY TEMPERATURE, DETERMINATION OF HORMONAL EXCRETION IN URINE, DETERMINATION OF HORMONAL LEVEL IN PLASMA, ULTRASOUND SCANNING, CERVICAL MUCUS PATTERN, , SIGNIFICANCE OF DETERMINING OVULATION TIME, , INTRODUCTION, Ovulation is the process by which the graafian follicle, in the ovary ruptures and the ovum is released into the, abdominal cavity. Ovulation occurs on the 14th day of, menstrual cycle in a normal cycle of 28 days., The ovum, which is released into the abdominal, cavity, enters the fallopian tube through the fimbriated, end of the tube. Usually, only one ovum is released from, any one of the ovaries. LH is responsible for ovulation., , PROCESS OF OVULATION, Prior to ovulation, large amount of LH is secreted (luteal, surge). This causes changes in the graafian follicle, leading to ovulation., Stages of Ovulation, 1. Graafian follicle moves towards the periphery of, ovary, 2. New blood vessels are formed in the ovary by, actions of LH and progesterone, 3. These blood vessels protrude into the wall of the, follicle, , 4. This increases the blood flow to the follicle, 5. Now, prostaglandin is released from granulosa cells, of the follicle, 6. It causes leakage of plasma into the follicle, 7. Just before ovulation the follicle swells and pro, trudes against the capsule of the ovary. This, protrusion is called stigma, 8. Then, progesterone activates the proteolytic, enzymes present in the cells of theca interna, 9. These enzymes weaken the follicular capsule and, cause degeneration of the stigma, 10. After about 30 minutes, fluid begins to ooze from, the follicle through the stigma, 11. It decreases the size of the follicle causing rupture, of stigma, 12. Now, ovum is released from the follicle along with, fluid and plenty of small granulosa cells into the, abdominal cavity (Fig. 81.1)., , HORMONAL REGULATION, OF OVULATION, Hormonal regulation of ovulation is discussed in the, previous chapter.
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Chapter 81 t Ovulation 493, DETERMINATION OF BASAL, BODY TEMPERATURE, Body temperature is measured for few days during the, mid period of menstrual cycle. Temperature is measured, in the morning by placing the thermometer in rectum or, vagina. There is a slight fall in the basal temperature, just prior to ovulation. And the temperature increases, after ovulation. The alteration in the temperature is, very mild and it is about ± 0.3°C to 0.5°C. The increase, in temperature is due to the thermogenic effect of, progesterone (Chapter 79)., DETERMINATION OF HORMONAL, EXCRETION IN URINE, At the time of ovulation, there is an increase in the urinary, excretion of metabolic end products of estrogen and, progesterone. The end products of estrogen metabolism, are estrone, estriol and 17-β-estradiol. The end product, of progesterone metabolism is pregnanediol., DETERMINATION OF HORMONAL, LEVEL IN PLASMA, Plasma level of FSH, LH, estrogen and progesterone, is measured. Hormone level is altered at the time of, ovulation and after ovulation., At the time of ovulation:, i. FSH level decreases, ii. LH level increases, iii. Estrogen level increases., After ovulation:, Progesterone level increases., ULTRASOUND SCANNING, , FIGURE 81.1: Process of ovulation, , Process of ovulation can be observed in ultrasound, scanning., CERVICAL MUCUS PATTERN, , DETERMINATION OF OVULATION TIME, Various methods are available to determine the ovu, lation time. In human beings, usually indirect methods, are adopted such as:, 1. Determination of basal body temperature, 2. Determination of hormonal excretion in urine, 3. Determination of hormonal level in plasma, 4. Ultrasound scanning, 5. Cervical mucus pattern., , When the cervical mucus spread on a slide is examined, under microscope, it shows a fern pattern. This pattern, disappears after ovulation., , SIGNIFICANCE OF DETERMINING, OVULATION TIME, Determination of ovulation time is helpful for family, planning by rhythm method (Chapter 88).
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Chapter, , Menopause, , 82, , CLIMACTERIC AND MENOPAUSE, CAUSE FOR MENOPAUSE, CHANGES DURING MENOPAUSE, , , , , CAUSE, SYMPTOMS, TREATMENT – HORMONE REPLACEMENT THERAPY (HRT), , CLIMACTERIC AND MENOPAUSE, Climacteric is the period in old age when reproductive, system undergoes changes due to the decreased, secretion of sex hormones, estrogen and progesterone., It occurs at the age of 45 to 55. In females, climacteric, is accompanied by menopause., Menopause is defined as the period when perma, nent cessation of menstruation takes place. Normally, it, occurs at the age of 45 to 55 years., In some women, the menstruation stops suddenly., In others, the menstrual flow decreases gradually during, every cycle and finally it stops. Sometimes irregular, menstruation occurs with lengthening or shortening of, the period with less or more flow., Early menopause may occur because of, surgical removal of ovaries (ovariectomy) or uterus, (hysterectomy) as a part of treatment for abnormal, menstruation. Usually, females with short menstrual, cycle attain menopause earlier than the females with, longer cycle. Cigarette smoking causes earlier onset of, menopause., , CAUSE FOR MENOPAUSE, Due to advancement of age, the atrophy of ovaries, occurs. It leads to the cessation of menstrual cycle, causing menopause. Throughout a woman’s sexual life,, about 450 of the primordial follicles grow into graafian, follicles and ovulate, while thousands of the follicles, degenerate., , At the age of 45 years, only few primordial follicles, remain in the ovary to be stimulated by FSH and LH., Now, the production of estrogen by ovary decreases, due to the decrease in the number of primordial, follicles. When estrogen secretion becomes almost, zero, FSH and LH are continuously secreted. When all, the primordial follicles are atrophied, estrogen secretion, stops completely., , CHANGES DURING MENOPAUSE –, POSTMENOPAUSAL SYNDROME, Postmenopausal syndrome is the group of symptoms, that appear in women immediately after menopause. It, is characterized by certain physical, physiological and, psychological changes. The symptoms start appearing, soon after the ovaries stop functioning., CAUSE, Major cause for the symptoms is the lack of estrogen, and progesterone. Symptoms may persist till the body, gets acclimatized to the absence of estrogen and, progesterone., SYMPTOMS, Symptoms do not appear in all women. Some women, develop mild symptoms and some women develop, severe symptoms, which last for few months to few, years.
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Chapter 82 t Menopause 495, Symptoms of postmenopausal syndrome:, 1. Hot flashes characterized by extreme flushing of, the skin: Hot flashes start with discomfort in the, abdomen and chill followed by the feeling of heat, spreading towards the head. Then the face becomes, red followed by sweating and exhaustion., 2. Vasomotor instability: Wide fluctuation in blood, pressure may be present. Blood pressure, increases suddenly and it comes back to normal, automatically., 3. Fatigue, 4. Nervousness, 5. Emotional outburst like crying and anger, 6. Mental depression, 7. Insomnia, 8. Palpitation, 9. Vertigo, 10. Headache, 11. Numbness or tingling sensation, 12. Urinary disturbances such as increased frequency, of micturition, , 13. Long-term effects of estrogen lack such as osteoporosis and atherosclerosis: Osteoporosis is the, bone disease resulting in reduction in bone mass., And the bones become susceptible for fracture., Atherosclerosis is the condition characterized by, deposition of cholesterol on the wall of the blood, vessels., TREATMENT – HORMONE, REPLACEMENT THERAPY, Most of the women manage it very well. But, about, 15% of the women need treatment. In many cases,, psychotherapy works very well. If it fails, hormone, replacement therapy (HRT) is given. Daily adminis, tration of estrogen in small quantities will reverse, the symptoms. The combination of estrogen and pro, gesterone is considered to be more advantageous, because progesterone prevents the estrogen-induced, cancer and hyperplasia of myometrium. Dose of the, hormones should be gradually reduced to prevent the, reoccurrence of postmenopausal symptoms.
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Chapter, , Infertility, , 83, , DEFINITION, INFERTILITY IN MALES, , , CAUSES, , INFERTILITY IN FEMALES, , , CAUSES, , DEFINITION, , 3. Obstruction of Reproductive Ducts, , Infertility is the inability to produce the offspring. In, females, it is the inability to conceive a child by natural, process or inability to carry pregnancy till the comple, tion of term. Infertility occurs due to various factors such, as immature reproductive system, defective reproductive, system, endocrine disorders, etc., , Obstruction of reproductive ducts like vas deferens, leads to infertility., , INFERTILITY IN MALES, CAUSES, 1. Decreased Sperm Count – Oligozoospermia, Normal sperm count in a male is about 100 to 150, millions/mL of semen. Infertility occurs when the sperm, count decreases below 20 millions/mL of semen. Sperm, count decreases because of disruption of seminiferous, tubules or acute infection in testis. In some males, there, is possibility of sterility (permanent inability to produce, offspring) because of absence of spermatogenesis as, in the case of cryptorchidism or underdeveloped testis, (Chapter 74)., 2. Abnormal Sperms, Sometimes, the sperm count may be normal, but the, structure of the sperm may be abnormal. The sperms, may be without tail and nonmotile or with two heads or, with abnormal head. When a large number of abnormal, sperms are produced infertility occurs (Chapter 77)., , 4. Other Disorders, i., ii., iii., iv., v., vi., vii., viii., , Cryptorchidism, Trauma, Mumps, Longterm use of drugs, Alcoholism, Genetic disorders, Hypothalamic disorders, Disorders of pituitary, thyroid and pancreas., , INFERTILITY IN FEMALES, CAUSES, 1. Abnormalities of Ovary, Sometimes, a thick capsule develops around the ovaries, and prevents ovulation. In some women, ovaries develop, cysts (membranous sac containing fluid) or become, fibrotic (hardened tissues resulting from lymphedema)., In these conditions, maturation and release of ovum, does not occur., 2. Abnormalities of Uterus, A type of endometrial tissue similar to uterine, endometrium grows in the pelvic cavity surrounding
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Chapter 83 t Infertility 497, the uterus, fallopian tubes and ovaries. It is called, endometriosis. And, pregnancy does not occur in this, condition., In some cases, there is low grade infection or, inflammation or abnormal hormonal stimulation in the, cervix. It leads to the abnormal secretion of thick mucus, in cervix, which prevents entry of sperm and fertilization, of ovum., 3. Absence of Ovulation, Ovulation does not occur in some females, because of, hyposecretion of gonadotropic hormones. Quantities, , of these hormones are not sufficient enough to cause, maturation of ovum or release of ovum. The cycle, without ovulation is known as anovulatory cycle., 4. Other Disorders, i., ii., iii., iv., v., , Diabetes mellitus, Renal diseases, Liver diseases, Hypothalamic disorders, Disorders of pituitary gland, thyroid and adrenal, glands.
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Pregnancy and Parturition, , Chapter, , 84, , INTRODUCTION, FERTILIZATION OF THE OVUM, SEX CHROMOSOMES AND SEX DETERMINATION, , , , SEX CHROMOSOMES, SEX DETERMINATION, , IMPLANTATION, DEVELOPMENT OF PLACENTA AND EMBRYO, MATERNAL CHANGES DURING PREGNANCY, , , , , , STRUCTURAL CHANGES, INCREASE IN BODY WEIGHT, METABOLIC CHANGES, CHANGES IN PHYSIOLOGICAL SYSTEMS, , GESTATION PERIOD, PARTURITION, , , , , , , , , BRAXTON HICKS CONTRACTIONS, FALSE LABOR CONTRACTIONS, STAGES OF PARTURITION, MECHANISM OF LABOR, ROLE OF UTERUS, ROLE OF CERVIX, ROLE OF HORMONES, , INTRODUCTION, Ovum is released from graafian follicle of ovary into the, abdominal cavity at the time of ovulation., From abdominal cavity, ovum enters fallopian tube, through the fimbriated end. Entry of ovum is facilitated, by movement of cilia present in the inner surface of, fimbriated end., Ovum of matured follicle in the ovary is in primary, oocyte stage with diploid number (23 pairs) of, chromosomes. Just before ovulation, meiotic division, takes place in the ovum. Primary oocyte divides into, a secondary oocyte and a first polar body. First polar, body is expelled out. Secondary oocyte contains only 23, chromosomes (haploid). Remaining 23 chromosomes, are lost in the expelled first polar body., , Thus, when the ovum is released into abdominal, cavity during ovulation, it is in the secondary oocyte, stage with haploid number of chromosomes., , FERTILIZATION OF THE OVUM, Fertilization refers to fusion (union) of male and female, gamates (sperm and ovum) to form a new offspring., If sexual intercourse occurs at ovulation time and, semen is ejaculated in the vagina, the sperms travel, through the vagina and uterus to reach the fallopian, tube. Sperms reach the ovarian end of fallopian tube, within 30 to 60 minutes., Movement of the sperm through uterus is facilitated, by the antiperistaltic contractions of uterine muscles., Uterine contractions are induced by oxytocin, which
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Chapter 84 t Pregnancy and Parturition 499, is secreted from posterior pituitary by neuroendocrine, reflex during sexual intercourse (Chapter 66). Uterine, contractions are also facilitated by prostaglandin (PGE2), present in male seminal fluid., Among 200 to 300 millions of sperms entering, female genital tract, only a few thousand sperms reach, the spot near the ovum. Among these few thousand, sperms, only one succeeds in fertilizing the ovum., During fertilization, the sperm enters the ovum, by penetrating the multiple layers of granulosa cells, known as corona radiata present around the ovum. It, is facilitated by hyaluronidase and proteolytic enzymes, present in acrosome of sperm. Proteolytic enzymes, from acrosome of the successful sperm diffuse through, the structures of zona pellucida and inactivate the other, sperms entering the ovum., Penetrating movement of sperm is enabled by a, protein called CatSper present in the tail portion of the, sperm. It is a tunnel-shaped protein and forms the ion, channel for entry of calcium into sperm cell., Immediately after fertilization, ovum, which is in, secondary oocyte stage, divides into a matured ovum, and a second polar body. Second polar body is expelled., Nucleus of matured ovum becomes female pronucleus, with 23 chromosomes, which include 22 autosomes and, one sex chromosome called X chromosome., Simultaneously, head of sperm swells and becomes, male pronucleus. Then 23 chromosomes of the sperm, and 23 chromosomes of ovum arrange themselves to, reform the 23 pairs of chromosomes in the fertilized, ovum., , SEX CHROMOSOMES AND, SEX DETERMINATION, SEX CHROMOSOMES, All the dividing cells in the body have 23 pairs of, chromosomes. Among the 23 pairs, 22 pairs are called, somatic chromosomes or autosomes. Remaining one, pair of chromosomes is called sex chromosomes. Sex, chromosomes are X and Y chromosomes., SEX DETERMINATION, Sex chromosomes are responsible for sex determination., During fertilization of ovum, 23 chromosomes from ovum, and 23 chromosomes from the sperm unite together to, form the 23 pairs (46) of chromosomes in the fertilized, ovum. Now, sex determination occurs. Ovum contains, the X chromosome. Sperm has either X chromosome or, Y chromosome. When the ovum is fertilized by a sperm, with X chromosome, the child will be female with XX, chromosome. And, if the ovum is fertilized by a sperm, , with Y chromosome, the sex of the child will be male, with XY chromosome. So, the sex of the child depends, upon the male partner., Role of testosterone in sex differentiation is explained in Chapter 74., , IMPLANTATION, Implantation is the process by which the fertilized ovum, called zygote implants (fixes itself or gets attached) in, the endometrial lining of uterus., After the fertilization, the ovum is known as zygote., Zygote takes 3 to 5 days to reach the uterine cavity from, fallopian tube. While travelling through the fallopian tube,, the zygote receives its nutrition from the secretions of, fallopian tube., After reaching the uterus, the developing zygote, remains freely in the uterine cavity for 2 to 4 days, before it is implanted. Thus, it takes about 1 week for, implantation after the day of fertilization. During the stay, in uterine cavity before implantation, the zygote receives, its nutrition from the secretions of endometrium, which, is known as uterine milk., Just before implantation, the zygote develops into, morula and then the implantation starts. A layer of, spherical cells called trophoblast cells is formed around, morula. Trophoblast cells release proteolytic enzymes, over the surface of endometrium. These enzymes, digest the cells of the endometrium. Now, morula moves, through the digested part of endometrium and implants, itself., , DEVELOPMENT OF PLACENTA, AND EMBRYO, Already uterus is prepared by progesterone secreted, from the corpus luteum during secretory phase of, menstrual cycle. After implantation, placenta develops, between morula and endometrium., When implantation occurs, there is further increase, in the thickness of endometrium because of continuous, secretion of progesterone from corpus luteum. At this, stage, the endometrial stromal cells are called decidual, cells and the endometrium at the implanted area is, called decidua., Now the trophoblastic cells of morula develop, into cords, which are attached with decidual portion of, endometrium. Blood capillaries grow into these cords, from the blood vessels of the newly formed embryo. At, about 16th day after fertilization, heart of embryo starts, pumping the blood into the trophoblastic cords., At the same time, blood sinusoids develop around, the trophoblastic cords. These sinusoids receive blood, from the mother.
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500 Section 7 t Reproductive System, Trophoblastic cells form some vascular projections, into which fetal capillaries grow. These vascular projections become placental villi., Thus, the final form of placenta has got the fetal part, and the maternal part., Fetal part of placenta contains the two umbilical, arteries, which carry fetal blood to the placental villi, through the capillaries. The blood returns back to fetus, through umbilical vein. Maternal part of placenta is, formed by uterine arteries through which blood flows, into sinusoids that surround the villi. The blood returns, back to mother’s body through uterine vein., Functions of placenta are described in detail in, Chapter 85., , MATERNAL CHANGES, DURING PREGNANCY, During pregnancy, the changes are noticed in various, organs, body weight, the metabolic activities and functional status of different physiological systems in the, mother., STRUCTURAL CHANGES, Various structural changes are noticed in the primary, sex organs, accessory sex organs and in the mammary, glands during pregnancy., 1. Ovaries, Follicular changes do not appear in ovary and ovulation, does not occur because the secretion of FSH and, LH from anterior pituitary is inhibited. Corpus luteum, enlarges and secretes a large quantity of progesterone, and little estrogen, which are essential for maintaining, the pregnancy. It continues for 3 months and then,, corpus luteum degenerates. By this time placenta, develops fully and takes over the function of secreting, estrogen and progesterone. It continues throughout the, period of pregnancy thus inhibiting the secretion of FSH, and LH., 2. Uterus, When the fetus grows, uterus undergoes changes in, volume, size, shape and weight., i. Volume, Volume of uterus increases gradually due to fetal, growth. From almost zero volume, uterus reaches about, 5 to 7 liters at the end of pregnancy. Out of this, 50%, of the volume is due to the fetus and rest is due to the, placenta, amniotic fluid, etc., , ii. Size, Size of the uterus also increases due to:, a. Hyperplasia (increase in number of cells) of, myometrium, b. Hypertrophy (increase in size of the cells) of, myometrium, c. Growth of fetus., iii. Shape, The shape of non-pregnant uterus is pyriform. As the fetus, grows, at the 12th week of pregnancy, it becomes globular., Then, once again it becomes pyriform gradually., iv. Weight, Non-pregnant uterus weighs about 30 to 50 g. The, weight increases as the pregnancy advances. At the, end of pregnancy, the uterine weight increases to about, 1,000 to 1,200 g., v. Histological changes, Endometrium shows formation of decidua, which is the, bed for the fertilized ovum during the initial stages of, pregnancy. Later, by the end of 3 months, three layers, of decidua are formed:, a. Decidua basalis, which is the maternal part, b. Decidua capsularis that surrounds fetal sac, c. Decidua parietalis, which lines rest of uterine, wall., After the 3rd month, the decidua capsularis and, parietalis fuse together., 3. Vagina, Vagina increases in size and its color changes to violet, due to increased blood supply. There is deposition of, glycogen in the epithelial cells., 4. Cervix, In cervix, the number of glands, blood supply and mucus, secretion increase. The tough cervix becomes soft and, it is closed by mucus plug., 5. Fallopian Tube, The number of epithelial cells and blood supply increase, in fallopian tubes., 6. Mammary Glands, Size of the mammary glands increases because of, development of new ducts and alveoli, deposition of fat, and increased vascularization. Pigmentation of nipple, and areola occurs.
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Chapter 84 t Pregnancy and Parturition 501, INCREASE IN BODY WEIGHT, Average weight gained by the body during pregnancy is, about 12 kg. Approximate weight of various structures,, which adds to the weight gain:, 1. Fetus, : 3.5 kg, 2. Amniotic fluid, : 2.0 kg, 3. Placenta, : 1.5 kg, 4. Increase in maternal : 5.0 kg, body weight, If proper prenatal care is not taken, the body weight, increases greatly by about 20 to 30 kg., METABOLIC CHANGES, The metabolic activities are accelerated in the body, due to increased secretion of various hormones like, thyroxine, cortisol and sex hormones., 1. Basal Metabolic Rate, Increase in the secretion of various hormones especially thyroxine increases the basal metabolic rate by, about 15% in the later stages of pregnancy., 2. Protein Metabolism, The anabolism of proteins increases during pregnancy., Positive nitrogen balance occurs. The deposition of, proteins increases in the uterus., , as well. Calcium and phosphorus are necessary for the, growing fetus., CHANGES IN PHYSIOLOGICAL SYSTEMS, 1. Blood, The blood volume increases by about 20% or about, 1 L. This increase is mainly because of increase in, plasma volume. It causes hemodilution. Because of, great demand for iron by the fetus, the mother usually, develops anemia. It can be rectified by proper prenatal, care and iron replacement., 2. Cardiovascular System, Cardiac output, Generally, cardiac output increases by about 30% in the, first trimester. After the 3rd month, cardiac output starts, decreasing and reaches almost the normal level in the, later stages of pregnancy., Blood pressure, Arterial blood pressure remains unchanged during, the first trimester. During the second trimester, there, is a slight decrease in blood pressure. It is due to the, diversion of blood to uterine sinuses. And, hypertension, develops if proper prenatal care is not taken., , 3. Carbohydrate Metabolism, , Pre-eclampsia, , Blood glucose level increases leading to glucosuria., Ketosis develops either due to less food or more vomiting., Because of all these reasons, there is hyperplasia of, beta cells of islets of Langerhans in pancreas leading to, increase in secretion of insulin. Inspite of this, there is, possibility of developing diabetes in pregnancy or latent, diabetes after delivery., , Pre-eclampsia is the hypertensive disorder of pregnancy., It is otherwise known as toxemia of pregnancy. About, 3% to 4% of the pregnant women suffer from this. It, usually occurs during last trimester of pregnancy., , 4. Lipid Metabolism, During pregnancy, there is deposition of about 3 to 4 kg, of fat in the maternal body. It also increases the blood, cholesterol level and ketosis., 5. Water and Mineral Metabolism, Estrogen and progesterone are secreted by corpus, luteum in the first trimester and by placenta later. These, hormones increase the retention of sodium and water., Secretion of aldosterone increases during pregnancy., Aldosterone in turn increases the reabsorption of, sodium from renal tubules. Apart from water and sodium, retention, there is retention of calcium and phosphorus, , Cause for hypertension, 1. Release of vasoconstrictor substances from, placenta, 2. Hypersecretion of adrenal hormones and other, hormones, which cause vasoconstriction, 3. Development of autoimmune processes induced, by the presence of placenta or fetus., Other symptoms associated with hypertension, 1. Decreased blood flow to kidney and thickening of, glomerular capillary membrane, leading to reduction in GFR and urinary output, 2. Retention of sodium and water, 3. Decreased urinary output along with retention of, sodium and water results in increased extracellular, fluid volume and edema, 4. Excretion of proteins through urine.
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502 Section 7 t Reproductive System, Eclampsia, Eclampsia is the serious condition of pre-ecclampsia, characterized by severe vascular spasm, dangerous, hypertension and convulsive muscular contractions, almost like seizures. It occurs just before, during or, immediately after delivery. It leads to death, if timely, treatment is not given., Features of eclampsia, 1., 2., 3., 4., 5., 6., 7., , Spasm of blood vessels, Very severe hypertension, Renal failure, Liver failure, Heart failure, Convulsions, Coma., , Treatment for eclampsia, Treatment should be immediate. It includes administration of, quick acting vasodilator drugs or termination of pregnancy., , and prolactin increases. However, the secretion of FSH, and LH decreases very much. It is because of negative, feedback control by estrogen and progesterone, which, are continuously secreted from corpus luteum initially, and placenta later on., ii. Adrenal cortex, There is moderate increase in secretion of cortisol,, which helps in the mobilization of amino acids from the, mother’s tissues to the fetus. Aldosterone secretion, also increases. It reaches the maximum at the end of, pregnancy. Along with estrogen and progesterone,, aldosterone is responsible for the retention of water and, sodium., iii. Thyroid gland, The size and the secretory activity of thyroid gland, increase during pregnancy. The increased secretion of, thyroxine helps in the preparation of mammary glands, for lactation. It is also responsible for increase in basal, metabolic rate., , 3. Respiratory System, , iv. Parathyroid glands, , Overall activity of respiratory system increases, slightly. Tidal volume, pulmonary ventilation and, oxygen utilization are increased., , Parathyroid glands also show an increase in the size, and secretory activity. Parathormone is responsible for, maintenance of calcium level in mother’s blood in spite, of loss of large amount of calcium to fetus., , 4. Excretory System, Renal blood flow and GFR increase resulting in, increase in urine formation. It is because of increase, in fluid intake and the increased excretory products, from fetus. The urine becomes diluted with the specific, gravity of 1,025. In the first trimester, the frequency of, micturition increases because of the pressure exerted, by the uterus on bladder., 5. Digestive System, During the initial stages of pregnancy, the morning, sickness occurs in mother. It involves nausea, vomiting, and giddiness. This is because of the hormonal imbalance. The motility of GI tract decreases by progesterone, and constipation is common. Indigestion and hypo, chlorhydria (decrease in the amount of hydrochloric, acid in gastric juice) also occur., 6. Endocrine System, i. Anterior pituitary, During pregnancy, the size of anterior pituitary increases, by about 50%. And secretion of corticotropin, thyrotropin, , 7. Nervous System, There is general excitement of nervous system during, pregnancy. It leads to the psychological imbalance, such as change in the moods, excitement or depression, in the early stages of pregnancy. During the later months, of pregnancy, the woman becomes very much excited, because of anticipation of delivery of the baby, labor, pain, etc., , GESTATION PERIOD, Gestation period refers to the pregnancy period. The, average gestation period is about 280 days or 40, weeks from the date of last menstrual period (LMP)., Traditionally, it is calculated as 10 lunar months., However, in terms of modern calendar it is calculated, as 9 months and 7 days. If the menstrual cycle is, normal 28 day cycle, the fertilization of ovum by the, sperm occurs on 14th day after LMP. Thus the actual, duration of human pregnancy is 280 – 14 = 266 days. If, the pregnancy ends before 28th week, it is referred as, miscarriage. If the pregnancy ends before 37th week,, then it is considered as premature labor.
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Chapter 84 t Pregnancy and Parturition 503, , PARTURITION, , Third Stage, , Parturition is the expulsion or delivery of the fetus from, the mother’s body. It occurs at the end of pregnancy., The process by which the delivery of fetus occurs is, called labor. It involves various activities such as, contraction of uterus, dilatation of cervix and opening, of vaginal canal., , During this stage, the placenta is detached from the, decidua and is expelled out from uterus. It occurs, within 10 to 15 minutes after the delivery of the child., , BRAXTON HICKS CONTRACTIONS, , MECHANISM OF LABOR, The slow and weak contractions of uterus commence at, about a month before parturition. Later, the contractions, gradually obtain strength and finally are converted into, labor contractions at the time of labor. Exact cause for, the onset of labor contractions is not known. It is strongly, believed that the labor contractions are induced by the, signal from fetus. And during labor, reflexes from uterus, and cervix produce the powerful uterine contractions., Thus, uterus and cervix play an important role in labor., Many hormones are also involved during parturition., , Braxton Hicks contractions are the weak, irregular,, short and usually painless uterine contractions, which, start after 6th week of pregnancy. These contractions, are named after the British doctor, John Braxton Hicks, who discovered them in 1872. It is suggested that these, contractions do not induce cervical dilatation but may, cause softening of cervix. Often called the practice, contractions, Braxton Hicks contractions help the, uterus practice for upcoming labor. Sometimes these, contractions cause discomfort., Braxton Hicks contractions are triggered by, several factors such as:, 1. Touching the abdomen, 2. Movement of fetus in uterus, 3. Physical activity, 4. Sexual intercourse, 5. Dehydration., , Once started, the uterine contractions cause the, development of more and more strong contractions. That, is, the irritation of uterine muscle during initial contraction, leads to further reflex contractions. It is called positive, feedback mechanism. It plays an important role, not, only in producing more number of uterine contractions, but also the contractions to become more and more, powerful., , FALSE LABOR CONTRACTIONS, , ROLE OF CERVIX, , While nearing the time of delivery, the Braxton Hicks, contractions become intense and are called false labor, contractions. The false labor contractions are believed, to help cervical dilatation., , Cervix also plays an important role in increasing the, strength of uterine contractions. When the head of fetus, is forced against the cervix during the first stage of labor,, the cervix stretches. It causes stimulation of muscles, of cervix, which in turn results in reflex contractions of, uterus., , STAGES OF PARTURITION, Parturition occurs in three stages:, First Stage, First, the strong uterine contractions called labor con, tractions commence. Labor contractions arise from, fundus of uterus and move downwards so that the head, of fetus is pushed against cervix. It results in dilatation, of cervix and opening of vaginal canal. Exact cause for, the onset of labor is not known. This stage extends for a, variable period of time., Second Stage, In this stage, the fetus is delivered out from uterus, through cervix and vaginal canal. This stage lasts for, about 1 hour., , ROLE OF UTERUS, , ROLE OF HORMONES, Hormones involved in the process of parturition:, Maternal Hormones, 1., 2., 3., 4., 5., , Oxytocin, Prostaglandins, Cortisol, Catecholamines, Relaxin., , Fetal Hormones, 1. Oxytocin, 2. Cortisol, 3. Prostaglandins.
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504 Section 7 t Reproductive System, Placental Hormones, 1. Estrogen, 2. Progesterone, 3. Prostaglandins., Estrogen, Estrogen is continuously secreted along with progesterone throughout the gestation period. However, in, the later period, the quantity of estrogen released is, much greater than that of progesterone., Estrogen:, i. Increases the force of uterine contractions, ii. Increases the number of oxytocin receptors in, uterine wall, iii. Accelerates the synthesis of prostaglandin from, uterus., Progesterone, Progesterone plays an important role in labor indirectly, by its sudden withdrawal at the end of pregnancy., Throughout the period of gestation, progesterone, suppresses uterine contractions. It also inhibits the, synthesis of prostaglandin (PGE2), which is necessary for, uterine contraction. Progesterone inhibits prostaglandin, synthesis by inhibiting the release of the enzyme, phospholipase A, which is essential for prostaglandin, synthesis., Sudden decrease in progesterone secretion at the, end of gestation period increases the uterine contractions, and PGE2 synthesis., Oxytocin, Oxytocin:, i. Causes contraction of smooth muscle of uterus, and enhances labor. During the later stages of, pregnancy, the number of receptors for oxytocin, increases in the wall of uterus by the influence of, estrogen. Because of this, the uterus becomes, more sensitive to oxytocin., ii. Stimulates the release of prostaglandins in the, decidua., Oxytocin is released in large quantity during labor. It, is due to neuroendocrine reflex. During the movement, of fetus through cervix, the receptors on the cervix are, stimulated and start discharging a large number of, impulses. Impulses are carried to hypothalamus by the, , somatic nerve fibers and result in the release of a large, quantity of oxytocin, which enhances labor. The release, of more amount of oxytocin occurs due to positive, feedback (Chapter 66)., Relaxin, Relaxin is secreted from maternal ovary (corpus luteum), during the initial period of pregnancy. It is secreted, in large quantity at the time of labor by placenta and, mammary glands (Chapter 87)., Relaxin:, i. Helps labor by softening the cervix and loosening, the ligaments of symphysis pubis, so that the, dilatation of cervix occurs, ii. Increases the number of receptors for oxytocin, in the myometrium, iii. Simultaneously suppresses the inhibitory action, of progesterone on uterine contraction so that, the uterus starts contracting, iv. Facilitates the development of mammary, glands., Prostaglandins, In recent times, prostaglandins are considered to, play a vital role in labor. Prostaglandins particularly, PGE2 facilitate labor by increasing the force of uterine, contractions. The prostaglandins are secreted from, uterine tissues, fetal membranes and placenta. Their, concentration is increased in maternal blood and, amniotic fluid at the time of labor., Prostaglandins increase the force of uterine, contractions by elevating the intracellular concentration, of calcium ions in the uterine muscles., Catecholamines, It is believed that the circulating adrenaline and noradrenaline also might increase the uterine contraction, through alpha adrenergic receptors., Cortisol, At the time of labor, hypothalamus releases large quantity of corticotropin-releasing hormone, which increases, the release of cortisol from the adrenal cortex. Cortisol, enhances the uterine contraction and plays an important, role in helping the mother to withstand the stress during, labor.
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Chapter, , Placenta, , 85, , INTRODUCTION, FUNCTIONS OF PLACENTA, , , , , , NUTRITIVE FUNCTION, EXCRETORY FUNCTION, RESPIRATORY FUNCTION, ENDOCRINE FUNCTION, , FETOPLACENTAL UNIT, , , FUNCTIONS OF FETOPLACENTAL UNIT, , INTRODUCTION, , EXCRETORY FUNCTION, , Placenta is a temporary membranous vascular organ, that develops in females during pregnancy. It is expelled, after childbirth. Placenta forms a link between the fetus, and mother. It is considered as an anchor for the growing, fetus. It is not only the physical attachment between, the fetus and mother, but also forms the physiological, connection between the two., Placenta is implanted in the wall of the uterus. It is, formed from both embryonic and maternal tissues. So,, it consists of two parts namely the fetal part and the, mother’s part. It is connected to the fetus by umbilical, cord, which contains blood vessels and connective, tissue. Development of placenta is explained in Chapter, 84., The delivery of fetus is followed by the expulsion of, placenta. After expulsion of the placenta, the umbilical, cord is cut. The site of attachment of placenta in the, center of anterior abdomen of fetus is called navel or, umbilicus., , Metabolic end products and other waste products from, the fetal body are excreted into the mother’s blood, through placenta., , FUNCTIONS OF PLACENTA, NUTRITIVE FUNCTION, Nutritive substances, electrolytes and hormones neces, sary for the development of fetus diffuse from mother’s, blood into fetal blood through placenta., , RESPIRATORY FUNCTION, Fetal lungs are nonfunctioning and placenta forms, the respiratory organ for fetus. Oxygen necessary for, fetus is received by diffusion from the maternal blood, and carbon dioxide from fetal blood diffuses into the, mother’s blood through placenta., Exchange of Respiratory Gases between, Fetal Blood and Maternal Blood, Exchange of respiratory gases between fetal blood, and maternal blood occurs mainly because of pressure, gradient. Partial pressure of oxygen in the maternal, blood is 50 mm Hg. In fetal blood, the partial pressure of, oxygen is 30 mm Hg. This pressure gradient of 20 mm Hg, causes the diffusion of oxygen into the fetal blood., This pressure gradient is very low, compared to the, gradient existing between partial pressure of oxygen in, arterial blood and alveoli in adults. Still, an adequate, quantity of oxygen is available for fetus., It is because of two reasons:, 1. The hemoglobin in fetal blood has 20 times more, affinity for oxygen than the adult hemoglobin
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506 Section 7 t Reproductive System, 2. The concentration of hemoglobin is about 50%, more in fetal blood than in adult blood., Bohr effect and Double Bohr effect, , 2. Estrogen, Placental estrogen is similar to ovarian estrogen in, structure and function., , Bohr effect is the decrease in the affinity of hemoglobin, for oxygen due to increased carbon dioxide tension., When carbon dioxide tension decreases, the affinity of, hemoglobin for oxygen is increased. All the metabolic, end products including carbon dioxide are completely, excreted from fetus into the maternal blood. This, develops low partial pressure of carbon dioxide in fetal, blood. So, the affinity of fetal hemoglobin for oxygen, increases resulting in diffusion of more amount of, oxygen from mother’s blood into fetal blood., At the same time, because of entrance of fetal carbon, dioxide into maternal blood, partial pressure of carbon, dioxide is very high in mother’s blood. It decreases the, affinity of mother’s hemoglobin for oxygen resulting in, diffusion of more amount of oxygen into the fetal blood., Double Bohr effect is the operation of Bohr effect in, both fetal blood and maternal blood., , Actions of placental estrogen, , ENDOCRINE FUNCTION, , i. On endometrium of uterus: Accelerates the, proliferation and development of decidual cells, in the endometrium of uterus. The decidual cells, are responsible for the supply of nutrition to the, embryo in the early stage., ii. On the movements of uterus: Inhibits the, contraction of muscles in the pregnant uterus., It is an important function of progesterone as it, prevents expulsion of fetus during pregnancy., iii. On breasts: Causes enlargement of breasts and, growth of duct system of the breasts., Progesterone is responsible for further development, and preparation of mammary glands for lactation., , Hormones secreted by placenta are:, 1. Human chorionic gonadotropin, 2. Estrogen, 3. Progesterone, 4. Human chorionic somatomammotropin, 5. Relaxin., 1. Human Chorionic Gonadotropin, Human chorionic gonadotropin (hCG) is a glycoprotein., Its chemical structure is similar to that of LH., Actions of hCG, i. On corpus luteum: hCG is responsible for the, preservation and the secretory activity of corpus, luteum. Progesterone and estrogen secreted by, corpus luteum are essential for the maintenance, of pregnancy. Deficiency or absence of hCG, during the first 2 months of pregnancy leads to, termination of pregnancy (abortion), because of, involution of corpus luteum., ii. On fetal testes: Action of hCG on fetal testes is, similar to that of LH in adults. It stimulates the, interstitial cells of Leydig and causes secretion, of testosterone. The testosterone is necessary, for the development of sex organs in male, fetus., , i. On uterus: Causes enlargement of the uterus so, that, the growing fetus can be accommodated., ii. On breasts: Responsible for the enlargement of, the breasts and growth of the duct system in the, breasts., iii. On external genitalia: Causes enlargement of, the female external genitalia., iv. On pelvis: Relaxes pelvic ligaments. It facilitates, the passage of the fetus through the birth canal, at the time of labor., 3. Progesterone, Placental progesterone is similar to ovarian progesterone, in structure and function., Actions of placental progesterone, , 4. Human Chorionic Somatomammotropin, Human chorionic somatomammotropin (HCS) is a, protein hormone secreted from placenta. It is often, called placental lactogen. It acts like prolactin and growth, hormone secreted from pituitary. So, it is believed to, act on mammary glands and to enhance the growth of, fetus by influencing the metabolic activities. It increases, the amount of glucose and lipids in the maternal blood,, which are transferred to fetus., Actions of HCS, i. On breasts: In experimental animals, adminis, tration of HCS causes enlargement of mammary, glands and induces lactation. That is why, it is
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Chapter 85 t Placenta 507, , FIGURE 85.1: Fetoplacental unit. DHEAS = Dehydroepiandrosterone sulfate,, 16OHDHEAS = 16hydoxydehydroepiandrosterone sulfate., , named as mammotropin. However, the action of, this hormone on the breasts of pregnant women, is not known., ii. On protein metabolism: HCS acts like GH on, protein metabolism. It causes anabolism of, proteins and accumulation of proteins in the fetal, tissues. Thus, the growth of fetus is enhanced., iii. On carbohydrate metabolism: It reduces the, peripheral utilization of glucose in the mother, leading to availability of large quantity of glucose, to the growing fetus., iv. On lipid metabolism: It mobilizes fat from the, adipose tissue of the mother. A large amount of, free fatty acid is made available as the source, of energy in the mother’s body. It compensates, the loss of glucose from the mother’s blood to, fetus., 5. Relaxin, Relaxin is a polypeptide, which is secreted by corpus, luteum. It is also secreted in large quantity by placenta, and mammary glands at the time of labor (Refer Chapter, 84)., , FETOPLACENTAL UNIT, Fetoplacental unit refers to the interaction between, fetus and placenta in the formation of steroid hormones., The interaction between fetus and placenta occurs, because some of the enzymes involved in steroid, synthesis present in fetus are absent in placenta and, those enzymes, which are absent in fetus are present, in placenta., , Due to this interaction during synthesis of steroid, hormones, fetus and placenta are together called, fetoplacental unit (Fig. 85.1)., FUNCTIONS OF FETOPLACENTAL UNIT, Placenta and fetus interact with each other in the, synthesis of steroid hormones in the following manner:, 1. Cholesterol, which is the precursor for steroid, hormones, is obtained by placenta from mother’s, blood, 2. Placenta synthesizes pregnenolone from cholesterol, 3. From pregnenolone, progesterone is formed, 4. Some amount of the pregnenolone from placenta, enters fetus. Fetal liver also produces a small, quantity of pregnenolone, 5. Pregnenolone from placenta and fetal liver forms, the substrate for the formation of two substances in, the adrenal gland of the fetus:, i. Dehydroepiandrosterone sulfate (DHEAS), ii. 16hydroxydehydroepiandrosterone, sulfate, (16OHDHEAS)., Some of the DHEAS is also hydroxylated into 16, OHDHEAS in fetal liver, 6. DHEAS and 16OHDHEAS are transported back, into the placenta to form estrogen, 7. Estradiol is synthesized from DHEAS and estriol, from 16OHDHEAS. These two forms of estrogen, enter mother’s blood, 8. Some amount of the progesterone enters the fetus, from placenta, 9. From this progesterone, cortisol and corticosterone, are synthesized in fetal adrenal glands.
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Chapter, , Pregnancy Tests, , 86, , INTRODUCTION, BIOLOGICAL TEST, IMMUNOLOGICAL TESTS, , INTRODUCTION, Pregnancy test is the test used to detect or confirm, pregnancy. The basis of pregnancy tests is to determine, the presence of the human chorionic gonadotropin, (hCG) in the urine of woman suspected for pregnancy., Both biological and immunological tests are available, to determine the presence of hCG in the urine of the, pregnant woman., , urine is injected subcutaneously into immature rat and, ovarian changes are observed after 6 hours. If the, urine is injected intraperitoneally, the ovarian changes, can be observed within 2 hours., FRIEDMAN TEST, In this test, 10 to 15 mL of urine is injected intravenously, into rabbit and ovulation is observed by examining the, ovaries after 48 hours., , BIOLOGICAL TESTS, , HOGBEN TEST, , These tests are performed by using experimental animals., The biological tests for pregnancy can be performed only, after 2 or 3 weeks of conception so that, the concentration, of hCG in urine is sufficient to show the result., , In this test, about 20 to 30 ml of urine is concentrated, and injected into the dorsal lymph sac of South African, toad, Xenopus levis. If hCG is present in the urine, it, causes ovulation after 12 hours., , ASCHHEIM-ZONDEK TEST, , GALLI-MAININI TEST, , Aschheim-Zondek test was the first test invented for, confirming the pregnancy. It depends upon the ovarian, changes in immature mice caused by hCG. The, immature mice do not ovulate naturally., Ovulation occurs only if hCG is injected. 2 mL of urine, from the woman suspected for pregnancy is injected daily, for 2 days into the immature mice. 5 days after injection, of urine, the mice are killed. The ovaries are examined for, the presence of corpora lutea (plural for corpus luteum), and hemorrhages, which indicates ovulation. Ovulation, is due to the presence of hCG in urine., , In this test, 2 mL of urine is injected into the male, amphibian (toad or frog). hCG in urine causes expulsion, of spermatozoa within 2 hours., Biological tests are outdated after the development, of immunological tests., , KUPPERMAN TEST, Kupperaman test is the modification of AschheimZondek test, in order to save time. In this, an immature, rat is used instead of immature mice. About 2 mL of, , Disadvantages of Biological Tests, Biological tests for pregnancy are replaced by, immunological tests because of several disadvantages:, 1. The biological test require animals, 2. Tests can be performed only after 2 to 3 weeks, of pregnancy so that sufficient quantity of hCG is, excreted in urine, 3. Results are not obtained quickly; one has to wait for, 2 to 48 hours, 4. Tests involve tedious procedures such as sacrificing, the animals.
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Chapter 86 t Pregnancy Tests 509, , IMMUNOLOGICAL TESTS, Presence of hCG is also determined by using, immunological techniques. Immunological tests, are based on double antigen-antibody reactions., Commonly performed immunological test is known as, Gravindex test., , PRINCIPLE, Principle is to determine the agglutination of sheep, RBCs coated with hCG. Latex particles could also be, used instead of sheep RBCs., REQUISITES, 1. Antiserum from Rabbit, Urine from a pregnant woman is collected and hCG is, isolated. This hCG is injected into a rabbit., The rabbit develops antibodies against hCG. The, antibodies are called hCG antibody or anti-hCG. The, rabbit’s blood is obtained and serum is separated., The serum containing hCG antibody is called rabbit, antiserum or hCG antiserum. It is readily available in, the market., , FIGURE 86.1: Immunological test for pregnancy, , free antibody is available. Agglutination of hCG molecules, by antibodies is not visible because it is colorless., Later when latex particles are added, these, particles are not agglutinated because, free antibody, is not available. Thus, absence of agglutination of latex, particles indicates that the woman is pregnant., Presence of Agglutination of Latex Particles, , 2. Red Blood Cells from Sheep, RBCs are obtained from sheep blood and are coated with, pure hCG obtained from urine of the pregnant women., Nowadays, instead of sheep RBCs, the rubberized, synthetic particles called the latex particles are used., 3. Urine, Fresh urine sample of the woman, who needs to confirm, pregnancy is used for Gravindex test., PROCEDURE, 1. One drop of hCG antiserum is taken on a glass, slide. One drop of urine from the woman who wants, to confirm pregnancy is added to this and both are, mixed well., 2. Now, one drop of latex particles is added to this and, mixed., OBSERVATION AND RESULT, Result is determined by observing the agglutination of, latex particles added to mixer of hCG antiserum and, woman’s urine., Absence of Agglutination of Latex Particles, If hCG is present in urine, it is agglutinated by antibodies, of antiserum and all the antibodies are fully used up. No, , If urine without hCG is mixed with antiserum, the, antibodies are freely available. When latex particles, are added, the antibodies cause agglutination of these, latex particles. Agglutination of latex particles can be, seen clearly even with naked eye. Thus, presence of, agglutination of latex particles indicates that, the woman, is not pregnant (Fig. 86.1)., ADVANTAGES OF IMMUNOLOGICAL, TESTS FOR PREGNANCY, 1. Immunological tests are more accurate, 2. Result is obtained quickly within few minutes, 3. These tests can be carried out very easily. The, procedure is not cumbersome, as in the case of, biological tests, 4. Immunological tests can be performed on 5th day, of conception. By biological methods, the tests can, be performed only after 2 or 3 weeks of conception., It is because, the concentration of hCG required, for producing changes in the animals is excreted in, urine only after 2 or 3 weeks of pregnancy, 5. Recently available immunological tests are more, sensitive and involve single step method. Test kit, is available in the form of cards. These pregnancy, test cards can be used even in the first few days, of conception. Most sensitive test can detect hCG, level as low as 20 mIU/mL.
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Chapter, , Mammary Glands, and Lactation, , , , , , 87, , DEVELOPMENT OF MAMMARY GLANDS, ROLE OF HORMONES IN GROWTH OF MAMMARY GLANDS, LACTATION, BREAST MILK, , DEVELOPMENT OF MAMMARY GLANDS, AT BIRTH, At the time of birth, mammary gland is rudimentary and, consists of only a tiny nipple and few radiating ducts, from it., , During the second half, there is enormous, growth of glandular tissues and the development is, completed for the production of milk just before the, end of gestation period., , ROLE OF HORMONES IN GROWTH, OF MAMMARY GLANDS, , AT CHILDHOOD, Till puberty, there is no difference in the structure of, mammary gland between male and female., AT PUBERTY, At the time of puberty and afterwards there is a vast, change in the structure of female mammary gland due, to hormonal influence. The beginning of changes in, mammary gland is called thelarche. It occurs at the, time of puberty, just before menarche (Chapter 80). At, puberty, there is growth of duct system and formation, of glandular tissue. During every sexual cycle, at the, time of menstruation there is slight regression and, in between the phases of menstruation, proliferative, changes occur. On the whole, progressive enlargement, occurs, which is also due to the deposition of fat., , Various hormones are involved in the development and, growth of breasts at different stages:, 1. Estrogen, 2. Progesterone, 3. Prolactin, 4. Placental hormones, 5. Other hormones., 1. ESTROGEN, Growth of Ductile System, Estrogen causes growth and branching of duct system;, so the normal development of duct system in breasts, at puberty depends upon estrogen. Estrogen is also, responsible for the accumulation of fat in breasts., , DURING PREGNANCY, , 2. PROGESTERONE, , During pregnancy, the mammary glands enlarge to, a great extent accompanied by marked changes, in structure. During first half of pregnancy, the duct, system develops further with appearance of many new, alveoli. No milk is secreted by the gland now., , Growth of Glandular Tissue, The development of stroma of the mammary glands, depends upon progesterone activity. Progesterone also, stimulates the development of glandular tissues.
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Chapter 87 t Mammary Glands and Lactation 511, 3. PROLACTIN, , Role of hormones in lactogenesis, , Prolactin is necessary for milk secretion. However,, it also plays an important role in growth of mammary, glands during pregnancy., Normally, prolactin is inhibited by prolactin-inhibiting, hormone secreted from hypothalamus. However, prolactin, secretion starts increasing from 5th month of pregnancy., At that time, it acts directly on the mammary glands and, causes proliferation of epithelial cells of alveoli., , Prolactin is responsible for lactogenesis. During pregnancy,, particularly in later months, large quantity of prolactin, is secreted. But the activity of this hormone is suppressed, by estrogen and progesterone secreted by placenta., Because of this, lactation is prevented during pregnancy., Immediately after the delivery of the baby and, expulsion of placenta, there is sudden loss of estrogen, and progesterone. Now, the prolactin is free to exert its, action on breasts and to promote lactogenesis., , 4. PLACENTAL HORMONES, Estrogen and progesterone secreted from placenta, are essential for further development of mammary, glands during pregnancy. Both the hormones stimulate, the proliferation of ducts and glandular cells during, pregnancy., 5. OTHER HORMONES, Growth hormone, thyroxine and cortisol enhance the, overall growth and development of mammary glands, in all stages. Relaxin also facilitates the development, of mammary glands. It is secreted by corpus luteum,, mammary glands and placenta. Its major function is to, facilitate dilatation of cervix during labor (Chapter 84)., , LACTATION, Lactation means synthesis, secretion and ejection of milk., Lactation involves two processes:, A. Milk secretion, B. Milk ejection., MILK SECRETION, Synthesis of milk by alveolar epithelium and its passage, through the duct system is called milk secretion., Milk secretion occurs in two phases:, 1. Initiation of milk secretion or lactogenesis, 2. Maintenance of milk secretion or galactopoiesis., 1. Initiation of Milk Secretion or Lactogenesis, Although small amount of milk secretion occurs at later, months of pregnancy, a free flow of milk occurs only, after the delivery of the child. The milk, which is secreted, initially before parturition is called colostrum., Colostrum is lemon yellow in color and it is rich in, protein (particularly globulins) and salts. But its sugar, content is low. It contains almost all the components of, milk except fat., , 2. Maintenance of Milk Secretion or Galactopoiesis, Galactopoiesis depends upon the hormones like growth, hormone, thyroxine and cortisol, which are essential, for continuous supply of glucose, amino acids, fatty, acids, calcium and other substances necessary for the, milk production (Fig. 87.1)., Role of hypothalamus in galactopoiesis, Galactopoiesis occurs till 7 to 9 months after delivery, of child provided feeding the baby with mother’s milk is, continued till then. In fact, the milk production is continued, only if feeding the baby is continued. Suckling of nipple by, the baby is responsible for continuous milk production., When the baby suckles, the impulses from touch, receptors around the nipple stimulate hypothalamus., It is suggested that hypothalamus releases some, prolactin-releasing factors, which cause the prolactin, secretion from anterior pituitary. Prolactin acts on, glandular tissues and maintains the functional activity, of breast for subsequent nursing., MILK EJECTION, Milk ejection is the discharge of milk from mammary, gland. It depends upon suckling exerted by the baby, and on contractile mechanism in breast, which expels, milk from alveoli into the ducts., Milk ejection is a reflex phenomenon. It is called, milk ejection reflex or milk let-down reflex. It is a, neuroendocrine reflex., , Milk Ejection Reflex, Milk ejection reflex is explained in Chapter 66., EFFECT OF LACTATION ON, MENSTRUAL CYCLE, Woman who nurses her child regularly does not have, menstrual cycle for about 24 to 30 weeks after delivery.
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512 Section 7 t Reproductive System, , FIGURE 87.1: Process of lactation and role of hormones, , It is because, regular nursing the baby stimulates, prolactin secretion continuously. Prolactin inhibits GnRH, secretion resulting in suppression of gonadotropin, secretion. In the absence of gonadotropin, the ovaries, become inactive and ovulation does not occur., When the frequency of nursing the baby decreases, (after about 24 weeks) the secretion of GnRH and, gonadotropins starts slowly. When sufficient quantity of, gonadotropins is secreted, the menstrual cycle starts., , BREAST MILK, Breast or human milk forms the primary source of, nutrition for infants., COMPOSITION, Breast milk contains about 88.5% of water and 11.5%, of solids. Important solids are lactose, lactalbumin, iron,, vitamins A and D and minerals., ADVANTAGES OF BREAST MILK, Breast milk is always considered superior to animal, milk (cow milk or goat milk) because it consists of, , sufficient quantity of all the substances necessary for, infants like iron, vitamins and minerals., Besides nourishment of infant, the breast milk, also provides several antibodies, which help the infant, resist the infection by lethal bacteria. Even some, neutrophils and macrophages are secreted in milk., These phagocytic cells protect the infant by destroying, microbes in the infant’s body., DISADVANTAGES OF ANIMAL MILK, 1. It causes irritation of GI tract and anemia, 2. Excess proteins and fats in animal milk are difficult, to digest and absorb by the infants, 3. High content of casein is harder to digest resulting, in GI bleeding and anemia, 4. High concentrations of sodium and potassium, in animal milk causes overstraining of immature, kidneys in infants, 5. Low iron content in animal milk develops iron defici, ency anemia, 6. It has low content of vitamins and essential fatty, acids.
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Chapter, , Fertility Control, , , , , , , 88, , INTRODUCTION, RHYTHM METHOD (SAFE PERIOD), MECHANICAL BARRIERS – PREVENTION OF ENTRY OF SPERM INTO UTERUS, CHEMICAL METHODS, ORAL CONTRACEPTIVES (PILL METHOD), , , , , , , CLASSICAL OR COMBINED PILLS, SEQUENTIAL PILLS, MINIPILLS OR MICROPILLS, DISADVANTAGES AND ADVERSE EFFECTS OF ORAL CONTRACEPTIVES, LONG-TERM CONTRACEPTIVES, , INTRAUTERINE CONTRACEPTIVE DEVICE (IUCD), , , , MECHANISM OF ACTION OF IUCD, DISADVANTAGES OF IUCD, , MEDICAL TERMINATION OF PREGNANCY (MTP) – ABORTION, , , , , DILATATION AND CURETTAGE (D AND C), VACUUM ASPIRATION, ADMINISTRATION OF PROSTAGLANDIN, , SURGICAL METHOD (STERILIZATION) – PERMANENT METHOD, , , , TUBECTOMY, VASECTOMY, , INTRODUCTION, Fertility control is the use of any method or device to, prevent pregnancy. It is also called birth control, family, planning or contraception. Fertility control techniques, may be temporary or permanent. Several methods are, available for fertility control., , RHYTHM METHOD (SAFE PERIOD), Rhythm method of fertility control is based on the, time of ovulation. After ovulation, i.e. on the 14th day, of menstrual cycle, the ovum is fertilized during its, passage through fallopian tubes. Its viability is only for, 2 days after ovulation and should be fertilized within, this period., Sperms survive only for about 24 to 48 hours, after ejaculation in the female genital tract. If sexual, , intercourse occurs during this period, i.e. between, few days before and few days after ovulation, there, is chance of pregnancy. This period is called the, dangerous period. Pregnancy can be avoided if there is, no sexual intercourse during this period. The prevention, of pregnancy by avoiding sexual mating during this, period is called rhythm method., The periods, when pregnancy does not occur are, 4 to 5 days after menstrual bleeding and 5 to 6 days, before the onset of next cycle. These periods are, together called safe period., Advantages and Disadvantages, It is one of the most successful methods of fertility, control provided the woman knows the exact day, of ovulation. However, it is not a successful method, because of various reasons. Basic knowledge about
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514 Section 7 t Reproductive System, the menstrual cycle is necessary to determine the day, of ovulation. Self-restraint is essential to avoid sexual, intercourse. Because of the practical difficulties, this, method is not popular., , MECHANICAL BARRIERS – PREVENTION, OF ENTRY OF SPERM INTO UTERUS, Mechanical barriers are used to prevent the entry of, sperm into uterine cavity. These barriers are called, condoms. The male condom is a leak proof sheath, made, of latex. It covers the penis and does not allow entrance, of semen into the female genital tract during coitus., In females, the commonly used condom is cervical, cap or diaphragm. It covers the cervix and prevents, entry of sperm into uterus., , CHEMICAL METHODS, Chemical substances, which destroy the sperms, are, applied in female genital tract before coitus. Destruction, of sperms is called spermicidal action. The spermicidal, substances are available in the form of foam tablet, jelly,, cream and paste., , ORAL CONTRACEPTIVES (PILL METHOD), Oral contraceptives are the drugs taken by mouth (pills), to prevent pregnancy. These pills prevent pregnancy by, inhibiting maturation of follicles and ovulation. This leads, to alteration of normal menstrual cycle. The menstrual, cycle becomes the anovulatory cycle., This method of fertility control is called pill method and, pills are called contraceptive pills or birth control pills., These pills contain synthetic estrogen and progesterone., Contraceptive pills are of three types:, 1. Classical or combined pills, 2. Sequential pills, 3. Minipills or micropills., 1. CLASSICAL OR COMBINED PILLS, Classical or combined pills contain a moderate dose, of synthetic estrogen like ethinyl estradiol or mestranol, and a mild dose of synthetic progesterone like norethindrone or norgestrol., Pills are taken daily from 5th to 25th day of, menstrual cycle. The withdrawal of the pills after 25th, day causes menstrual bleeding. The intake of pills is, resumed again after 5th day of the next cycle., , It suppresses the release of gonadotropins, FSH and, LH from pituitary by means of feedback mechanism., Lack of FSH and LH prevents the maturation of follicle,, and ovulation. In addition, progesterone increases the, thickness of mucosa in cervix, which is not favorable, for transport of sperm. When the pills are withdrawn, after 21 days the menstrual flow starts., 2. SEQUENTIAL PILLS, Sequential pills contain a high dose of estrogen along, with moderate dose of progesterone. These pills also, prevent ovulation., Sequential pills are taken in two courses:, i. Daily for 15 days from 5th to 20th day of the, menstrual cycle and then, ii. During the last 5 days, i.e. 23rd to 28th day., 3. MINIPILLS OR MICROPILLS, Minipills contain a low dose of only progesterone, and are taken throughout the menstrual cycle. It, prevents pregnancy without affecting ovulation. The, progesterone increases the thickness of cervical, mucosa, so that the transport of sperms is inhibited. It, also prevents implantation of ovum., DISADVANTAGES AND ADVERSE EFFECTS, OF ORAL CONTRACEPTIVES, About 40% of women who use contraceptive pills may, have minor transient side effects. However, long term, use of oral contraceptives causes some serious side, effects. Some of the side effects are rare, but may be, dangerous., Following are the disadvantages and adverse, effects of oral contraceptives:, 1. Major practical difficulty is the regular intake of the, pills, 2. May not be suitable for women having disorders, such as diabetes, cardiovascular diseases or liver, diseases, 3. Clotting tendency of blood due to suppressed, production of anticoagulants in liver, 4. Hypertension and heart attack, 5. Increases the risk of stroke, 6. Tenderness of breast and risk of breast cancer, (but may decrease the risk of ovarian and uterine, cancer)., LONG-TERM CONTRACEPTIVES, , Mechanism of Action, During the continuous intake of the pills, there is relatively, large amount of estrogen and progesterone in the blood., , To avoid taking pills daily, the long-term contraceptives, are used. These contraceptives are in the form of, implants containing mainly progesterone. The implants,
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Chapter 88 t Fertility Control 515, TABLE 88.1: Contraceptive methods in, males and females, , which are inserted beneath the skin release the drug, slowly and prevent fertility for 4 to 5 years. Though it, seems to be effective, it may produce amenorrhea., , Males, , Females, , INTRAUTERINE CONTRACEPTIVE DEVICE, (IUCD) – PREVENTION OF FERTILIZATION, AND IMPLANTATION OF OVUM, , Rhythm method, , Fertilization and the implantation of ovum are prevented, by inserting some object made from metal or plastic, into uterine cavity. Such object is called intrauterine, contraceptive device (IUCD)., , Chemical, methods, , Chemical substances, applied in genital, tract, , Oral, contraceptives, , Classical pills, Sequential pills, Mini pills, , Implants, , Intrauterine, contraceptive, device:, Lippe loop, Copper T, , Medical, termination, of pregnancy, (MTP), , Dilation and curettage, Vacuum aspiration, Prostaglandin, administration, , Condom, , Safe period, Male condom, , MECHANISM OF ACTION OF IUCD, Intrauterine contraceptive device prevents fertilization, and implantation of the ovum. The IUCD with copper, content has spermicidal action also. The IUCD which, is loaded with synthetic progesterone slowly releases, progesterone. Progesterone causes thickening of cervical mucus and prevents entry of sperm into uterus., The common IUCDs are Lippes loop, which is ‘S’, shaped and made of plastic and copper T, which is, made up of copper. It is inserted into the uterine cavity, by using some special applicator., , Surgical, method, (sterilization), , Vasectomy, , Cervical cap, Diaphragm, , Tubectomy, , DISADVANTAGES OF IUCD, IUCD has some disadvantages. It has the tendency to:, 1. Cause heavy bleeding in some women, 2. Promote infection, 3. Come out of uterus accidentally., , MEDICAL TERMINATION, OF PREGNANCY (MTP) – ABORTION, Abortion is done during first few months of pregnancy., This method is called medical termination of pregnancy, (MTP). There are three ways of doing MTP (Table 88.1)., DILATATION AND CURETTAGE (D AND C), In this method, the cervix is dilated and the implanted, ovum or zygote is removed., VACUUM ASPIRATION, The implanted ovum is removed by vacuum aspiration, method. This is done up to 12 weeks of pregnancy., ADMINISTRATION OF PROSTAGLANDIN, Administration of prostaglandin like PGE2 and PGF2, intravaginally increases uterine contractions resulting, in abortion., , SURGICAL METHOD (STERILIZATION) –, PERMANENT METHOD, Permanent sterility is obtained by surgical methods. It is, also called sterilization., TUBECTOMY, In tubectomy, the fallopian tubes are cut and both the, cut ends are ligated. It prevents entry of ovum into, uterus. The operation is done through vaginal orifice in, the postpartum period. During other periods, it is done, by abdominal incision. Tubectomy is done quickly (in, few minutes) by using a laparoscope., Though tubectomy causes permanent sterility, if, necessary recanalization of fallopian tube can be done, using plastic tube by another surgical procedure., VASECTOMY, In vasectomy, the vas deferens is cut and the cut ends, are ligated. So the sperms cannot enter the ejaculatory, duct and the semen is devoid of sperms. It is done by, surgical procedure with local anesthesia. If necessary,, the recanalization of vas deferens can be done with, plastic tube.
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516 Questions in Reproductive System, , QUESTIONS IN REPRODUCTIVE SYSTEM, , LONG QUESTIONS, 1. Describe the functions of testis and regulation of, testicular functions., 2. Describe the actions and regulation of secretion, of testosterone., 3. What are the female sex hormones? Explain their, actions., 4. What is menstrual cycle? Explain the ovarian, changes taking place during menstrual cycle., 5. Describe the uterine changes during menstrual, cycle., 6. Give an account of menstrual cycle and explain, the hormonal regulation of menstrual cycle., 7. Give an account of lactation. And, add a note on, the role of various hormones in the development, of mammary glands and lactation., , SHORT QUESTIONS, 1., 2., 3., 4., 5., 6., 7., 8., 9., 10., 11., 12., 13., 14., 15., , Gametogenic function of testis or spermatogenesis., Endocrine functions of testis., Sertoli cells., Testosterone., Cryptorchidism., Secondary sexual characters in males., Puberty in males., Seminal vesicles., Prostate gland., Semen., Spermatozoa., Effects of removal of testes., Hyper and hypogonadism in males., Estrogen., Progesterone., , 16., 17., 18., 19., 20., 21., 22., 23., 24., 25., 26., 27., 28., 29., 30., 31., 32., 33., 34., 35., 36., 37., 38., 39., 40., 41., 42., 43., 44., 45., 46., 47., 48., , Follicle-stimulating hormone., Luteinizing hormone., Gonadotropins., Secondary sexual characters in females., Puberty in females., Ovarian follicles., Graafian follicle., Ovulation., Corpus luteum., Hormonal regulation of menstrual cycle., Menopause., Infertility in females., Infertility in males., Maternal changes during pregnancy., Functions of placenta., Placental hormones., Fetoplacental unit., Parturition., Pregnancy tests., Role of hormones in lactation., Prolactin., Lactation., Milk ejection reflex., Oxytocin., Safe period/Rhythm method., Condoms., Oral contraceptives., IUCD., MTP., Vasectomy., Tubectomy., Contraceptive methods in females., Contraceptive methods in males.
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Section, , 8, , 89., 90., 91., 92., 93., 94., 95., 96., 97., 98., 99., 100., 101., 102., 103., 104., 105., , Cardiovascular, System, , Introduction to Cardiovascular System ................................................... 519, Properties of Cardiac Muscle .................................................................. 525, Cardiac Cycle .......................................................................................... 533, Heart Sounds .......................................................................................... 544, Cardiac Murmur ...................................................................................... 549, Electrocardiogram (ECG) ........................................................................ 551, Vector ...................................................................................................... 558, Arrhythmia ............................................................................................... 562, Effect of Changes in Electrolyte Concentration on Heart ........................ 570, Cardiac Output ........................................................................................ 572, Heart-lung Preparation ............................................................................ 582, Cardiac Function Curves ......................................................................... 584, Heart Rate ............................................................................................... 587, Hemodynamics ....................................................................................... 595, Arterial Blood Pressure ........................................................................... 602, Venous Pressure ..................................................................................... 617, Capillary Pressure ................................................................................... 620
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106., 107., 108., 109., 110., 111., 112., 113., 114., 115., 116., 117., , Arterial Pulse ........................................................................................... 622, Venous Pulse .......................................................................................... 627, Coronary Circulation ............................................................................... 629, Cerebral Circulation ................................................................................ 634, Splanchnic Circulation ............................................................................. 638, Capillary Circulation ................................................................................ 640, Circulation through Skeletal Muscle ........................................................ 644, Cutaneous Circulation ............................................................................. 646, Fetal Circulation and Respiration ............................................................ 648, Hemorrhage ............................................................................................ 651, Circulatory Shock and Heart Failure ....................................................... 654, Cardiovascular Adjustments during Exercise .......................................... 664
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Introduction to, Cardiovascular System, , Chapter, , 89, , CARDIOVASCULAR SYSTEM, HEART, , , , , , , , , , RIGHT SIDE, LEFT SIDE, SEPTA, LAYERS OF THE WALL, PERICARDIUM, MYOCARDIUM, ENDOCARDIUM, VALVES, , ACTIONS OF THE HEART, , , , , , CHRONOTROPIC ACTION, INOTROPIC ACTION, DROMOTROPIC ACTION, BATHMOTROPIC ACTION, , BLOOD VESSELS, , , , , ARTERIAL SYSTEM, VENOUS SYSTEM, COMPLICATIONS IN BLOOD VESSELS, , DIVISIONS OF CIRCULATION, , , , SYSTEMIC CIRCULATION, PULMONARY CIRCULATION, , CARDIOVASCULAR SYSTEM, Cardiovascular system includes heart and blood, vessels. Heart pumps blood into the blood vessels., Blood vessels circulate the blood throughout the body., Blood transports nutrients and oxygen to the tissues, and removes carbon dioxide and waste products from, the tissues., , HEART, Heart is a muscular organ that pumps blood throughout, the circulatory system. It is situated in between two lungs, in the mediastinum. It is made up of four chambers, two, atria and two ventricles. The musculature of ventricles, , is thicker than that of atria. Force of contraction of heart, depends upon the muscles., RIGHT SIDE OF THE HEART, Right side of the heart has two chambers, right atrium, and right ventricle. Right atrium is a thin walled and, low pressure chamber. It has got the pacemaker known, as sinoatrial node that produces cardiac impulses and, atrioventricular node that conducts the impulses to the, ventricles., Right atrium receives venous (deoxygenated) blood, via two large veins:, 1. Superior vena cava that returns venous blood from, the head, neck and upper limbs
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520 Section 8 t Cardiovascular System, 2. Inferior vena cava that returns venous blood from, lower parts of the body (Fig. 89.1)., Right atrium communicates with right ventricle, through tricuspid valve. Wall of right ventricle is thick., Venous blood from the right atrium enters the right, ventricle through this valve., From the right ventricle, pulmonary artery arises. It, carries the venous blood from right ventricle to lungs. In, the lungs, the deoxygenated blood is oxygenated., LEFT SIDE OF THE HEART, Left side of the heart has two chambers, left atrium, and left ventricle. Left atrium is a thin walled and low, pressure chamber. It receives oxygenated blood from, the lungs through pulmonary veins. This is the only, exception in the body, where an artery carries venous, blood and vein carries the arterial blood., Blood from left atrium enters the left ventricle through, mitral valve (bicuspid valve). Wall of the left ventricle, is very thick. Left ventricle pumps the arterial blood to, different parts of the body through systemic aorta., , and left ventricles are separated from one another by, interventricular septum. The upper part of this septum, , is a membranous structure, whereas the lower part of it, is muscular in nature., LAYERS OF WALL OF THE HEART, Heart is made up of three layers of tissues:, 1. Outer pericardium, 2. Middle myocardium, 3. Inner endocardium., PERICARDIUM, Pericardium is the outer covering of the heart. It is made, up of two layers:, i. Outer parietal pericardium, ii. Inner visceral pericardium., The space between the two layers is called, pericardial cavity or pericardial space and it contains, a thin film of fluid., i. Outer Parietal Pericardium, , SEPTA OF THE HEART, Right and left atria are separated from one another, by a fibrous septum called interatrial septum. Right, , Parietal pericardium forms a strong protective sac for, the heart. It helps also to anchor the heart within the, mediastinum., , FIGURE 89.1: Section of the heart
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Chapter 89 t Introduction to Cardiovascular System 521, Parietal pericardium is made up two layers:, a. Outer fibrous layer, b. Inner serous layer., , Important difference between skeletal muscle, and cardiac muscle is that the cardiac muscle fiber is, branched and the skeletal muscle is not branched., , Fibrous layer, , Intercalated disk, , Fibrous layer of the parietal pericardium is formed by, thick fibrous connective tissue. It is attached to the, diaphragm and it is continuous with tunica adventitia, (outer wall) of the blood vessels, entering and leaving, the heart. It is attached with diaphragm below. Because, of the fibrous nature, it protects the heart from over, stretching., , Intercalated disk is a tough double membranous, structure, situated at the junction between the branches, of neighboring cardiac muscle fibers. It is formed by the, fusion of the membrane of the cardiac muscle branches, (Fig. 89.2)., Intercalated disks form adherens junctions, which, play an important role in the contraction of cardiac, muscle as a single unit (Chapter 2)., , Serous layer, Serous layer is formed by mesothelium, together with, a small amount of connective tissue. Mesothelium, contains squamous epithelial cells which secrete a, small amount of fluid, which lines the pericardial space., This fluid prevents friction and allows free movement of, heart within pericardium, when it contracts and relaxes., The total volume of this fluid is only about 25 to 35 mL., ii. Inner Visceral Pericardium, Inner visceral pericardium lines the surface of, myocardium. It is made up of flattened epithelial cells., This layer is also known as epicardium., MYOCARDIUM, Myocardium is the middle layer of wall of the heart, and it is formed by cardiac muscle fibers or cardiac, myocytes. Myocardium forms the bulk of the heart and, it is responsible for pumping action of the heart. Unlike, skeletal muscle fibers, the cardiac muscle fibers are, involuntary in nature., Refer Chapter 28 for features of cardiac muscles., Myocardium has three types of muscle fibers:, i. Muscle fibers which form contractile unit of, heart, ii. Muscle fibers which form pacemaker, iii. Muscle fibers which form conductive system., , Syncytium, Syncytium means tissue with cytoplasmic continuity, between adjacent cells. However, cardiac muscle, is like a physiological syncytium, since there is no, continuity of the cytoplasm and the muscle fibers are, separated from each other by cell membrane. At the, sides, the membranes of the adjacent muscle fibers, fuse together to form gap junctions. Gap junction is, permeable to ions and it facilitates the rapid conduction, of action potential from one fiber to another. Because, of this, all the cardiac muscle fibers act like a single, unit, which is referred as syncytium., Syncytium in human heart has two portions,, syncytium of atria and the syncytium of ventricles. Both, the portions of syncytium are connected by a thick nonconducting fibrous ring called the atrioventricular ring., ii. Muscle Fibers which Form the Pacemaker, Some of the muscle fibers of heart are modified into a, specialized structure known as pacemaker. These muscle, fibers forming the pacemaker have less striation., Pacemaker, Pacemaker is structure in the heart that generates the, impulses for heart beat. It is formed by pacemaker cells, , i. Muscle Fibers which Form Contractile, Unit of Heart, These cardiac muscle fibers are striated and resemble, the skeletal muscle fibers in structure. Cardiac muscle, fiber is bound by sarcolemma. It has a centrally placed, nucleus. Myofibrils are embedded in the sarcoplasm., Sarcomere of the cardiac muscle has all the contractile, proteins, namely actin, myosin, troponin and, tropomyosin. Sarcotubular system in cardiac muscle is, similar to that of skeletal muscle., , FIGURE 89.2: Cardiac muscle fibers
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522 Section 8 t Cardiovascular System, called P cells. Sinoatrial (SA) node forms the pacemaker, in human heart. Details of pacemaker are given in next, chapter., iii. Muscle Fibers which Form Conductive System, Conductive system of the heart is formed by modified, cardiac muscle fibers. Impulses from SA node, are transmitted to the atria directly. However, the, impulses are transmitted to ventricles through various, components of conducting system, which are explained, in the next chapter., ENDOCARDIUM, Endocardium is the inner most layer of heart wall. It is a, thin, smooth and glistening membrane. It is formed by a, single layer of endothelial cells, lining the inner surface, of the heart. Endocardium continues as endothelium of, the blood vessels., VALVES OF THE HEART, There are four valves in human heart. Two valves are in, between atria and the ventricles called atrioventricular, valves. Other two are the semilunar valves, placed at, the opening of blood vessels arising from ventricles,, namely systemic aorta and pulmonary artery. Valves of, the heart permit the flow of blood through heart in only, one direction., Atrioventricular Valves, Left atrioventricular valve is otherwise known as mitral, valve or bicuspid valve. It is formed by two valvular cusps, or flaps (Fig. 89.3). Right atrioventricular valve is known, as tricuspid valve and it is formed by three cusps., Brim of the atrioventricular valves is attached to, atrioventricular ring, which is the fibrous connection, between the atria and ventricles. Cusps of the valves, are attached to papillary muscles by means of chordae, tendineae. Papillary muscles arise from inner surface, of the ventricles. Papillary muscles play an important, role in closure of the cusps and in preventing the back, flow of blood from ventricle to atria during ventricular, contraction., Atrioventricular valves open only towards ventricles, and prevent the backflow of blood into atria., Semilunar Valves, Semilunar valves are present at the openings of systemic, aorta and pulmonary artery and are known as aortic, valve and pulmonary valve respectively. Because of the, , FIGURE 89.3: Valves of the heart, , half moon shape, these two valves are called semilunar, valves. Semilunar valves are made up of three flaps., Semilular valves open only towards the aorta and, pulmonary artery and prevent the backflow of blood into, the ventricles., , ACTIONS OF THE HEART, Actions of the heart are classified into four types:, 1. Chronotropic action, 2. Inotropic action, 3. Dromotropic action, 4. Bathmotropic action., CHRONOTROPIC ACTION, Chronotropic action is the frequency of heartbeat or, heart rate. It is of two types:, i. Tachycardia or increase in heart rate, ii. Bradycardia or decrease in heart rate., INOTROPIC ACTION, Force of contraction of heart is called inotropic action. It, is of two types:, i. Positive inotropic action or increase in the force, of contraction, ii. Negative inotropic action or decrease in the, force of contraction.
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Chapter 89 t Introduction to Cardiovascular System 523, DROMOTROPIC ACTION, Dromotropic action is the conduction of impulse through, heart. It is of two types:, i. Positive dromotropic action or increase in the, velocity of conduction, ii. Negative dromotropic action or decrease in the, velocity of conduction., BATHMOTROPIC ACTION, Bathmotropic action is the excitability of cardiac muscle., It is also of two types:, i. Positive bathmotropic action or increase in the, excitability of cardiac muscle, ii. Negative bathmotropic action or decrease in the, excitability of cardiac muscle., Regulation of Actions of Heart, All the actions of heart are continuously regulated. It is, essential for the heart to cope up with the needs of the, body. All the actions are altered by stimulation of nerves, supplying the heart or some hormones or hormonal, substances secreted in the body., , BLOOD VESSELS, Vessels of circulatory system are the aorta, arteries,, arterioles, capillaries, venules, veins and venae cavae., Structural differences between different blood vessels, are given in Table 89.1., ARTERIAL SYSTEM, Arterial system comprises the aorta, arteries and, arterioles. Walls of the aorta and arteries are formed by, three layers:, 1. Outer tunica adventitia, which is made up of connective tissue layer. It is the continuation of fibrous, layer of parietal pericardium., , 2. Middle tunica media, which is formed by smooth, muscles, 3. Inner tunica intima, which is made up of endothelium., It is the continuation of endocardium., Aorta, arteries and arterioles have two laminae of, elastic tissues:, i. External elastic lamina between tunica adventitia, and tunica media, ii. Internal elastic lamina between tunica media, and tunica intima., Aorta and arteries have more elastic tissues and the, arterioles have more smooth muscles., Arterial branches become narrower and their walls, become thinner while reaching the periphery. Aorta has, got the maximum diameter of about 25 mm. Diameter, of the arteries is gradually decreased and at the end, arteries, it is about 4 mm. It further decreases to 30 µ, in the arterioles and ends up with 10 µ in the terminal, arterioles. Resistance (peripheral resistance) is offered, to blood flow in the arterioles and so these vessels are, called resistant vessels., Arterioles are continued as capillaries, which are, small, thin walled vessels having a diameter of about, 5 to 8 µ. Capillaries are functionally very important, because, the exchange of materials between the blood, and the tissues occurs through these vessels., VENOUS SYSTEM, From the capillaries, venous system starts and it includes venules, veins and venae cavae. Capillaries end in, venules, which are the smaller vessels with thin muscular, wall than the arterioles. Diameter of the venules is, about 20 µ. At a time, a large quantity of blood is held in, venules and hence the venules are called capacitance, vessels. Venules are continued as veins, which have, the diameter of 5 mm. Veins form superior and inferior, venae cavae, which have a diameter of about 30 mm., , TABLE 89.1: Structural and dimensional differences between different blood vessel walls, Blood vessel, , Diameter, , Thickness of, the wall, , Elastic tissue, , Smooth muscle, fibers, , Fibrous tissue, , Aorta, , 25 mm, , 2 mm, , More, , Less, , More, , Artery, , 4 mm, , 1 mm, , More, , More, , Moderate, , Arteriole, , 30 µ, , 6 µ, , Moderate, , More, , Moderate, , Terminal arteriole, , 10 µ, , 2 µ, , Less, , More, , Moderate, , 8 µ, , 0.5 µ, , Absent, , Absent, , Moderate, , 20 µ, , 1 µ, , Absent, , Absent, , Less, , 5 mm, , 0.5 mm, , Less, , More, , Moderate, , 30 mm, , 1.5 mm, , Less, , More, , More, , Capillary, Venule, Vein, Vena cava
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524 Section 8 t Cardiovascular System, Walls of the veins and venae cavae are made up of, inner endothelium, elastic tissues, smooth muscles and, outer connective tissue layer. In the veins and venae, cavae, the elastic tissue is less but the smooth muscle, fibers are more., COMPLICATIONS IN BLOOD VESSELS, Aorta and Arteries, Arterial blood vessels are highly susceptible for, arteriosclerosis and atherosclerosis. Arteriosclerosis is, the disease of the arteries, associated with hardening,, thickening and loss of elasticity in the wall of the, vessels. Atherosclerosis is the disease marked by the, narrowing of lumen of arterial vessel due to deposition, of cholesterol., Arterioles, When the tone of the smooth muscles in the arterioles, increases, hypertension occurs., Capillaries, Permeability of the capillary membrane may increase, resulting in shock or edema due to leakage of fluid,, proteins and other substances from blood., , FIGURE 89.4: Systemic and pulmonary circulation, , Inflammation of the wall of veins leads to the formation, of intravascular clot called thrombosis. The clot gets, dislodged, as thrombus. The thrombus travels through, blood and causes embolism. Embolism obstructs the, blood flow to vital organs such as brain, heart and lungs,, leading to many complications., , and reaches the tissues. Exchange of various, substances between blood and the tissues occurs at, the capillaries., After exchange of materials, blood enters the, venous system and returns to right atrium of the heart., From right atrium, blood enters the right ventricle., Thus, through systemic circulation, oxygenated, blood is supplied from heart to the tissues and venous, blood returns to the heart from tissues., , DIVISIONS OF CIRCULATION, , PULMONARY CIRCULATION, , Blood flows through two divisions of circulatory system:, 1. Systemic circulation, 2. Pulmonary circulation., , Pulmonary circulation is otherwise called lesser, circulation. Blood is pumped from right ventricle to lungs, through pulmonary artery. Exchange of gases occurs, between blood and alveoli of the lungs at pulmonary, capillaries. Oxygenated blood returns to left atrium, through the pulmonary veins., Thus, left side of the heart contains oxygenated or, arterial blood and the right side of the heart contains, deoxygenated or venous blood., , Veins, , SYSTEMIC CIRCULATION, Systemic circulation is otherwise known as greater, circulation (Fig. 89.4). Blood pumped from left ventricle, passes through a series of blood vessels, arterial system
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Chapter, , Properties of, Cardiac Muscle, , 90, , EXCITABILITY, , , , , , DEFINITION, ELECTRICAL POTENTIALS IN CARDIAC MUSCLE, IONIC BASIS OF ACTION POTENTIAL, SPREAD OF ACTION POTENTIAL THROUGH CARDIAC MUSCLE, , RHYTHMICITY, , , , , DEFINITION, PACEMAKER, ELECTRICAL POTENTIAL IN SINOATRIAL NODE, , CONDUCTIVITY, , , , CONDUCTIVE SYSTEM IN HUMAN HEART, VELOCITY OF IMPULSES AT DIFFERENT PARTS OF CONDUCTIVE SYSTEM, , CONTRACTILITY, , , , , , ALL-OR-NONE LAW, STAIRCASE PHENOMENON, SUMMATION OF SUBLIMINAL STIMULI, REFRACTORY PERIOD, , EXCITABILITY, , Action Potential, , DEFINITION, , Action potential in cardiac muscle is different from that, of other tissues such as skeletal muscle, smooth muscle, and nervous tissue. Duration of the action potential in, cardiac muscle is 250 to 350 msec (0.25 to 0.35 sec)., , Excitability is defined as the ability of a living tissue to, give response to a stimulus. In all the tissues, initial, response to a stimulus is electrical activity in the form of, action potential. It is followed by mechanical activity in, the form of contraction, secretion, etc., ELECTRICAL POTENTIALS, IN CARDIAC MUSCLE, Refer Chapter 31 for basics of electrical potentials in, the muscle., , Phases of action potential, Action potential in a single cardiac muscle fiber occurs, in four phases:, 1. Initial depolarization, 2. Initial repolarization, 3. A plateau or final depolarization, 4. Final repolarization., , Resting Membrane Potential, Resting membrane potential in:, Single cardiac muscle fiber : – 85 to – 95 mV, Sinoatrial (SA) node, : – 55 to – 60 mV, Purkinje fibers, : – 90 to – 100 mV., , 1. Initial Depolarization, Initial depolarization is very rapid and it lasts for about 2, msec (0.002 sec). Amplitude of depolarization is about, + 20 mV (Fig. 90.1).
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526 Section 8 t Cardiovascular System, suddenly and slow sodium channels open, resulting in, slow influx of low quantity of sodium ions., 3. Plateau or Final Depolarization, Plateau is due to the slow opening of calcium, channels. These channels are kept open for a longer, period and cause influx of large number of calcium, ions. Already the slow sodium channels are opened,, , FIGURE 90.1: Action potential in ventricular muscle., 1 = Depolarization, 2 = Initial rapid repolarization, 3 = Plateau,, 4 = Final repolarization., , 2. Initial Repolarization, Immediately after depolarization, there is an initial rapid, repolarization for a short period of about 2 msec. The, end of rapid repolarization is represented by a notch., , through which slow influx of sodium ions continues., Because of the entry of calcium and sodium ions into, the muscle fiber, positivity is maintained inside the, muscle fiber, producing prolonged depolarization, i.e., plateau. Calcium ions entering the muscle fiber play an, important role in the contractile process., 4. Final Repolarization, , Final repolarization is due to efflux of potassium, ions. Number of potassium ions moving out of the, muscle fiber exceeds the number of calcium ions, moving in. It makes negativity inside, resulting in final, repolarization. Potassium efflux continues until the end, of repolarization., , 3. Plateau or Final Depolarization, Afterwards, the muscle fiber remains in depolarized, state for sometime before further repolarization. It forms, the plateau (stable period) in action potential curve. The, plateau lasts for about 200 msec in atrial muscle fibers, and for about 300 msec in ventricular muscle fibers., Due to long plateau in action potential, the contraction, time is also longer in cardiac muscle by 5 to 15 times, than in skeletal muscle., 4. Final Repolarization, Final repolarization occurs after the plateau. It is a slow, process and it lasts for about 50 to 80 msec before the, re-establishment of resting membrane potential., , Restoration of Resting Membrane Potential, At the end of final repolarization, all sodium ions, which, had entered the cell throughout the process of action, potential move out of the cell and potassium ions move, into the cell, by activation of sodium-potassium pump., Simultaneously, excess of calcium ions, which had, entered the muscle fiber also move out through sodiumcalcium pump. Thus, the resting membrane potential is, restored., SPREAD OF ACTION POTENTIAL, THROUGH CARDIAC MUSCLE, , Initial depolarization (first phase) is because of rapid, opening of fast sodium channels and the rapid influx of, sodium ions, as in the case of skeletal muscle fiber., , Action potential spreads through cardiac muscle very, rapidly because of the presence of gap junctions, between the cardiac muscle fibers. Gap junctions are, permeable junctions and allow free movement of ions, and so the action potential spreads rapidly from one, muscle fiber to another fiber., Action potential is transmitted from atria to ventricles, through the fibers of specialized conductive system,, which is explained later in this chapter., , 2. Initial Repolarization, , RHYTHMICITY, , IONIC BASIS OF ACTION POTENTIAL, 1. Initial Depolarization, , Initial repolarization is due to the transient (short, duration) opening of potassium channels and efflux, of a small quantity of potassium ions from the muscle, fiber. Simultaneously, the fast sodium channels close, , DEFINITION, Rhythmicity is the ability of a tissue to produce its own, impulses regularly. It is also called autorhythmicity or
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Chapter 90 t Properties of Cardiac Muscle 527, self-excitation. Property of rhythmicity is present in all, the tissues of heart. However, heart has a specialized, excitatory structure, from which the discharge of, impulses is rapid. This specialized structure is called, pacemaker. From here, the impulses spread to other, parts through the specialized conductive system., , 3. Atrial muscle, : 40 to 60/minute, 4. Purkinje fibers, : 35 to 40/minute, 5. Ventricular muscle : 20 to 40/minute., Pacemaker in Amphibian Heart, , Pacemaker is the structure of heart from which the, impulses for heartbeat are produced. It is formed by the, pacemaker cells called P cells. In mammalian heart, the, pacemaker is sinoatrial node (SA node). It was Lewis Sir, Thomas, who named SA node as pacemaker of heart,, in 1918., , Sinus venosus is the pacemaker in amphibian heart. It, is experimentally proved by:, 1. Applying Stannius ligatures, 2. When sinus venosus is warmed by warm Ringer, solution, heart rate increases, 3. When sinus venosus is cooled by cold Ringer, solution, heart rate decreases, 4. Electrical activity starts first in sinus venosus., , Sinoatrial Node, , Stannius ligature experiment, , Sinoatrial (SA) node is a small strip of modified cardiac, muscle, situated in the superior part of lateral wall of right, atrium, just below the opening of superior vena cava., The fibers of this node do not have contractile elements., These fibers are continuous with fibers of atrial muscle,, so that the impulses from the SA node spread rapidly, through atria., Other parts of heart such as atrioventricular (AV), node, atria and ventricle also can produce the impulses, and function as pacemakers. Still, SA node is called the, pacemaker because the rate of production of impulse, (rhythmicity) is more in SA node than in other parts. It is, about 70 to 80/minute., , Stannius ligature experiment was demonstrated by, German biologist Stannius in a pithed frog. Ligature, means tying. Pithing is a process by which the brain and, spinal cord are severed by using a needle, to abolish all, the reflex activities during the experiment. Pithed frog is, technically dead but some of its organs such as heart,, continue to function for some time., Chest wall of a pithed frog is opened and heart, is exposed. A bent pin is fixed at the tip of ventricle, and attached to a recording device by means of a, thread. After recording the normal heartbeats (normal, cardiogram or sinus rhythm), a ligature is applied, between the sinus venosus and right auricle. It is called, first Stannius ligature., When this ligature is applied, the heart stops, beating immediately. It is because the impulses, produced by sinus venosus cannot be conducted, to the other chambers of the heart. However, the, sinus contractions are continued. After sometime,, auricular muscle becomes the pacemaker and starts, producing the impulses for heartbeat, but at a slower, rate. Auricular contraction occurs first, followed by, ventricular contraction. This rhythm of the heart is called, auriculoventricular rhythm (Fig. 90.2)., When a second ligature is applied between auricles, and ventricle, the heart stops beating again, because, impulses from auricles cannot reach the ventricle. After, few minutes, the ventricle produces its own impulses, and starts beating but at a much slower rate. The slow, independent ventricular rhythm is called idioventricular, rhythm. Thus, all the three parts of the heart, sinus, venosus, auricular musculature and ventricular musculature have the property of rhythmicity. However,, sinus venosus is the pacemaker because it produces, the impulses at a faster rate., , PACEMAKER, , Experimental Evidences, Experimental evidences to prove that SA node is the, pacemaker in mammalian heart:, 1. Stimulation of SA node accelerates the heart rate, 2. Destruction of SA node causes immediate stoppage, of the heartbeat. After sometime, atrioventricular, node becomes the pacemaker and starts generating, the impulses. So the heart starts beating, but the, rate is slow., 3. Local cooling of SA node decreases the heart rate, 4. Local warming of SA node increases the heart rate, 5. Electrical activity starts first in SA node., Spread of Impulses from SA Node, Mammalian heart has got a specialized conductive, system, by which the impulses from SA node spreads to, other parts of the heart (see below)., Rhythmicity of Different Parts of Human Heart, 1. SA node, 2. AV node, , : 70 to 80/minute, : 40 to 60/minute
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528 Section 8 t Cardiovascular System, , FIGURE 90.2: Effect of Stannius ligatures on frog’s heart, , Spread of Impulses from Sinus Venosus, Amphibian heart does not have any specialized, conductive system. Pacemaker in amphibian heart is, the sinus venosus and impulses from sinus venosus, spreads through the muscles of auricles and ventricle., Rhythmicity of Different Parts of Amphibian Heart, 1. Sinus venosus, : 40 to 60/minute, 2. Auricular muscle, : 20 to 40/minute, 3. Ventricular muscle : 15 to 20/minute., ELECTRICAL POTENTIAL IN SA NODE, Resting Membrane Potential – Pacemaker Potential, Pacemaker potential is the unstable resting membrane, potential in SA node. It is also called prepotential., Electrical potential in SA node is different from that, of other cardiac muscle fibers. In SA node, each impulse, triggers the next impulse. It is mainly due to the unstable, resting membrane potential., Resting membrane potential in SA node has, a negativity of –55 to –60 mV. It is different from the, negativity of –85 to –95 mV in other cardiac muscle, fibers., , FIGURE 90.3: Pacemaker potential, , Action Potential, Depolarization starts very slowly and the threshold level, of –40 mV is reached very slowly. After the threshold, level, rapid depolarization occurs up to +5 mV. It is, followed by rapid repolarization. Once again, the resting, membrane potential becomes unstable and reaches the, threshold level slowly (Fig. 90.3)., , Ionic Basis of Electrical Activity in Pacemaker, Pacemaker potential or resting membrane potential, Resting membrane potential is not stable in the SA, node. To start with, the sodium ions leak into the, pacemaker fibers and cause slow depolarization. This
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Chapter 90 t Properties of Cardiac Muscle 529, slow depolarization forms the initial part of pacemaker, potential. Then, the calcium channels start opening., At the beginning, there is a slow influx of calcium ions, causing further depolarization in the same slower rate. It, forms the later part of the pacemaker potential., Thus, the initial part of pacemaker potential is due, to slow influx of sodium ions and the later part is due to, the slow influx of calcium ions., Depolarization, When the negativity is decreased to –40 mV, which is, the threshold level, the action potential starts with rapid, depolarization. The depolarization occurs because of, influx of more calcium ions. Unlike in other tissues, the, depolarization in SA node is mainly due to the influx of, calcium ions, rather than sodium ions., Repolarization, After rapid depolarization, repolarization starts. It is, due to the efflux of potassium ions from pacemaker, fibers. Potassium channels remain open for a longer, time, causing efflux of more potassium ions. It leads, to the development of more negativity, beyond the level, of resting membrane potential. It exists only for a short, period. Then, the slow depolarization starts once again,, leading to the development of pacemaker potential,, which triggers the next action potential., , CONDUCTIVITY, Human heart has a specialized conductive system,, through which impulses from SA node are transmitted, to all other parts of the heart (Fig. 90.4)., , CONDUCTIVE SYSTEM IN HUMAN HEART, Conductive system of the heart is formed by the modified, cardiac muscle fibers. These fibers are the specialized, cells, which conduct the impulses rapidly from SA node, to the ventricles. Conductive tissues of the heart are, also called the junctional tissues., Components of Conductive System, in Human Heart, 1., 2., 3., 4., , AV node, Bundle of His, Right and left bundle branches, Purkinje fibers., SA node is situated in right atrium, just below the, opening of superior vena cava. AV node is situated in, right posterior portion of intra-atrial septum. Impulses, from SA node are conducted throughout right and, left atria. Impulses also reach the AV node via some, specialized fibers called internodal fibers., There are three types of internodal fibers:, 1. Anterior internodal fibers of Bachman, 2. Middle internodal fibers of Wenckebach, 3. Posterior internodal fibers of Thorel., All these fibers from SA node converge on AV, node and interdigitate with fibers of AV node. From, AV node, the bundle of His arises. It divides into right, and left branches, which run on either side of the, interventricular septum. From each branch of bundle, of His, many Purkinje fibers arise and spread all over, the ventricular myocardium., , FIGURE 90.4: Sinoatrial node and conductive system of the heart
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530 Section 8 t Cardiovascular System, VELOCITY OF IMPULSES AT DIFFERENT, PARTS OF CONDUCTIVE SYSTEM, 1., 2., 3., 4., 5., 6., , Atrial muscle fibers, : 0.3 meter/second, Internodal fibers, : 1.0 meter/second, AV node, : 0.05 meter/second, Bundle of His, : 0.12 meter/second, Purkinje fibers, : 4.0 meter/second, Ventricular muscle fibers : 0.5 meter/second., Thus, the velocity of impulses is maximum in, Purkinje fibers and minimum at AV node., , CONTRACTILITY, Contractility is ability of the tissue to shorten in length, (contraction) after receiving a stimulus. Various factors, affect the contractile properties of the cardiac muscle., Following are the contractile properties:, ALL-OR-NONE LAW, According to all-or-none law, when a stimulus is applied,, whatever may be the strength, the whole cardiac, muscle gives maximum response or it does not give, any response at all. Below the threshold level, i.e. if the, strength of stimulus is not adequate, the muscle does, not give response., All-or-none law is demonstrated in the quiescent, (quiet) heart of frog. Heart is made quiescent by applying, the first Stannius ligature in between the sinus venosus, and right auricle., Ventricle is stimulated by placing the electrode at, the base of ventricle., First, one stimulus is applied with a minimum strength, of 1 volt at the base of ventricle and the contraction, is recorded. Then, after 20 seconds, the strength of, stimulus is increased to 2 volt and the stimulus is applied., , The curve is recorded. The procedure is repeated by, increasing the strength every time and applying the, stimulus with an interval of 20 seconds (Fig. 90.5)., Amplitude of all contractions remains the same,, irrespective of increasing the strength of stimulus. This, shows that cardiac muscle obeys all-or-none law., Cause for All-or-none law, All-or-none law is applicable to whole cardiac muscle., It is because of syncytial arrangement of cardiac, muscle. In the case of skeletal muscle, all-or-none law, is applicable only to a single muscle fiber., STAIRCASE PHENOMENON, When the ventricle of a quiescent heart of frog is, stimulated at a short interval of 2 seconds, without, changing the strength, the force of contraction increases, gradually for the first few contractions and then it remains, same. Gradual increase in the force of contraction is, called staircase phenomenon., Cause for Staircase Phenomenon, Staircase phenomenon occurs because of beneficial, effect (Chapter 30), which facilitates the force of, successive contraction. So, there is a gradual increase, in force of contraction (Fig. 90.5)., SUMMATION OF SUBLIMINAL STIMULI, When a stimulus with a subliminal strength is applied,, the quiescent heart does not show any response. When, few stimuli with same subliminal strength are applied in, succession, the heart shows response by contraction,, due to the summation of stimuli., , FIGURE 90.5: All-or-none law and staircase phenomenon in cardiac muscle
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Chapter 90 t Properties of Cardiac Muscle 531, REFRACTORY PERIOD, Refractory period is the period in which the muscle does, not show any response to a stimulus. It is of two types:, 1. Absolute refractory period, 2. Relative refractory period., Absolute Refractory Period, Absolute refractory period is the period during which the, muscle does not show any response at all, whatever, may be the strength of the stimulus. It is because, the, depolarization occurs during this period. So, a second, depolarization is not possible., , its duration is 0.27 sec. Relative refractory period extends, during first half of relaxation period, which is about 0.26, sec. So, the total refractory period is 0.53 sec., Significance of Long Refractory Period, in Cardiac Muscle, Long refractory period in cardiac muscle has three, advantages:, 1. Summation of contractions does not occur, 2. Fatigue does not occur, 3. Tetanus does not occur., Demonstration of Refractory Period in Heart, , Relative Refractory Period, Relative refractory period is the period during which, the muscle shows response if the strength of stimulus, is increased to maximum. It is the stage at which the, muscle is in repolarizing state., Refractory Period in Skeletal Muscle, In skeletal muscle, the refractory period is short., Absolute refractory period extends during the first, half of latent period, measuring about 0.005 sec., Relative refractory period extends during the second, half of latent period measuring 0.005 sec. So, the total, refractory period is 0.01 sec., Refractory Period in Cardiac Muscle, Cardiac muscle has a long refractory period compared, to skeletal muscle. Absolute refractory period extends, throughout the contraction period of cardiac muscle and, , Refractory period is demonstrated in the heart of a, pithed frog. Refractory period can be recorded in, beating heart as well as the quiescent heart., Refractory period in beating heart, First, normal cardiogram is recorded with the heart of, a pithed frog. The impulses for heartbeat arise from, the sinus venosus. An electrical (external) stimulus, is applied by keeping the electrode at the base of the, ventricle. When the stimulus is applied during systole,, the heart does not show any response. It is because the, absolute refractory period extends throughout systole, (Fig. 90.6)., When a stimulus is applied during diastole, the, heart contracts because, diastole is the relative, refractory period. This contraction of the heart is called, extrasystole or premature contraction. Etrasystole is, followed by the stoppage of heart in diastole for a while., This diastole is longer than the diastole after regular, , FIGURE 90.6: Refractory period in beating heart of frog
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532 Section 8 t Cardiovascular System, contraction. Temporary stoppage of the heart before, it starts contracting is called compensatory pause., Duration of extrasystole and compensatory pause is, equivalent to the duration of two cardiac cycles., Cause for compensatory pause, A natural impulse from sinus venosus arrives at the time, of contraction period of extrasystole. As this period is, absolute refractory period, the natural impulse cannot, cause contraction of heart. And the heart has to wait for, the arrival of next natural impulse from sinus venosus. Till, the arrival of next impulse, the heart stops in diastole., Refractory period in quiescent heart, Frog’s heart is made quiescent by applying the first, Stannius ligature. Electrode is placed over the base of, ventricle. When two stimuli are applied successively, in such a way that the second stimulus falls during, contraction period, the heart contracts only once. It, is because of the first stimulus. There is no response, to second stimulus because systole is the absolute, , FIGURE 90.7: Refractory period in quiescent heart of a frog., PS1 = Point of first stimulus, PS2 = Point of second stimulus., , refractory period. However, when a second stimulus is, applied during diastole, the heart contracts again and, second contraction superimposes over the first one., This shows that the relative refractory period extends, during diastole (Fig. 90.7).
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Cardiac Cycle, , Chapter, , 91, , DEFINITION, EVENTS, DIVISIONS AND DURATION, , , , ATRIAL EVENTS, VENTRICULAR EVENTS, , DESCRIPTION OF ATRIAL EVENTS, , , , ATRIAL SYSTOLE, ATRIAL DIASTOLE, , DESCRIPTION OF VENTRICULAR EVENTS, , , , , , , , , ISOMETRIC CONTRACTION PERIOD, EJECTION PERIOD, PROTODIASTOLE, ISOMETRIC RELAXATION PERIOD, RAPID FILLING PHASE, SLOW FILLING PHASE, LAST RAPID FILLING PHASE, , INTRA-ATRIAL PRESSURE CHANGES DURING CARDIAC CYCLE, , , , , , SIGNIFICANCE, METHODS OF STUDY, MAXIMUM AND MINIMUM PRESSURE IN ATRIA, INTRA-ATRIAL PRESSURE CURVE, , INTRAVENTRICULAR PRESSURE CHANGES DURING CARDIAC CYCLE, , , , , , SIGNIFICANCE, METHODS OF STUDY, MAXIMUM AND MINIMUM PRESSURE IN VENTRICLES, INTRAVENTRICULAR PRESSURE CURVE, , AORTIC PRESSURE CHANGES DURING CARDIAC CYCLE, , , , , , SIGNIFICANCE, METHOD OF STUDY, MAXIMUM AND MINIMUM PRESSURE IN AORTA, AORTIC PRESSURE CURVE, , VENTRICULAR VOLUME CHANGES DURING CARDIAC CYCLE, , , , , , SIGNIFICANCE, METHODS OF STUDY, VOLUME OF BLOOD IN RIGHT AND LEFT VENTRICLES, VENTRICULAR VOLUME CURVE
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534 Section 8 t Cardiovascular System, , DEFINITION, Cardiac cycle is defined as the succession of (sequence, of) coordinated events taking place in the heart during, each beat. Each heartbeat consists of two major, periods called systole and diastole. During systole,, heart contracts and pumps the blood through arteries., During diastole, heart relaxes and blood is filled in the, heart. All these changes are repeated during every, heartbeat, in a cyclic manner., , EVENTS OF CARDIAC CYCLE, Events of cardiac cycle are classified into two:, 1. Atrial events, 2. Ventricular events., , DIVISIONS AND DURATION, OF CARDIAC CYCLE, When the heart beats at a normal rate of 72/minute,, duration of each cardiac cycle is about 0.8 second., , DESCRIPTION OF ATRIAL EVENTS, ATRIAL SYSTOLE, Atrial systole is also known as last rapid filling phase or, presystole. It is usually considered as the last phase of, ventricular diastole. Its duration is 0.11 second., During this period, only a small amount, i.e. 10% of, blood is forced from atria into ventricles. Atrial systole is, not essential for the maintenance of circulation. Many, persons with atrial fibrillation survive for years, without, suffering from circulatory insufficiency. However, such, persons feel difficult to cope up with physical stress like, exercise., Pressure and Volume Changes, , ATRIAL EVENTS, Atrial events are divided into two divisions:, 1. Atrial systole, = 0.11 (0.1) sec, 2. Atrial diastole, = 0.69 (0.7) sec., , During atrial systole, the intraatrial pressure increases., Intraventricular pressure and ventricular volume also, increase but slightly., Fourth Heart Sound, , VENTRICULAR EVENTS, Ventricular events are divided into two divisions:, 1. Ventricular systole, = 0.27 (0.3) sec, 2. Ventricular diastole, = 0.53 (0.5) sec., In clinical practice, the term ‘systole’ refers to ven, tricular systole and ‘diastole’ refers to ventricular diastole., Ventricular systole is divided into two subdivisions and, ventricular diastole is divided into five subdivisions., Ventricular Systole, 1. Isometric contraction, 2. Ejection period, , Among the atrial events, atrial systole occurs during, the last phase of ventricular diastole. Atrial diastole is, not considered as a separate phase, since it coincides, with the whole of ventricular systole and earlier part of, ventricular diastole., , Time (second), = 0.05, = 0.22, 0.27, , Contraction of atrial musculature causes the production, of fourth heart sound., ATRIAL DIASTOLE, After atrial systole, the atrial diastole starts. Simultane, ously, ventricular systole also starts. Atrial diastole, lasts for about 0.7 sec (accurate duration is 0.69 sec)., This long atrial diastole is necessary because, this is, the period during which atrial filling takes place. Right, atrium receives deoxygenated blood from all over the, body through superior and inferior venae cavae. Left, atrium receives oxygenated blood from lungs through, pulmonary veins., Atrial Events Vs Ventricular Events, , Ventricular Diastole, 1., 2., 3., 4., 5., , Protodiastole, Isometric relaxation, Rapid filling, Slow filling, Last rapid filling, , =, =, =, =, =, , 0.04, 0.08, 0.11, 0.19, 0.11, 0.53, , Out of 0.7 sec of atrial diastole, first 0.3 sec (0.27 sec, accurately) coincides with ventricular systole. Then,, ventricular diastole starts and it lasts for about 0.5, sec (0.53 sec accurately). Later part of atrial diastole, coincides with ventricular diastole for about 0.4 sec. So,, the heart relaxes as a whole for 0.4 sec. Figure 91.1, shows the correlation between atrial and ventricular, events of cardiac cycle.
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Chapter 91 t Cardiac Cycle 535, increases above the pressure in the aorta and, pulmonary artery, the semilunar valves open. Thus,, the pressure rise in ventricle, caused by isometric, contraction is responsible for the opening of semilunar, valves, leading to ejection of blood from the ventricles, into aorta and pulmonary artery., EJECTION PERIOD, Due to the opening of semilunar valves and isotonic, contraction of ventricles, blood is ejected out of both the, ventricles. Hence, this period is called ejection period., Duration of this period is 0.22 second. Ejection period, is of two stages:, 1. First Stage or Rapid Ejection Period, First stage starts immediately after the opening of, semilunar valves. During this stage, a large amount of, blood is rapidly ejected from both the ventricles. It lasts, for 0.13 second., FIGURE 91.1: Atrial and ventricular events of cardiac cycle, , DESCRIPTION OF VENTRICULAR EVENTS, ISOMETRIC CONTRACTION PERIOD, Isometric contraction period in cardiac cycle is the first, phase of ventricular systole. It lasts for 0.05 second., Isometric contraction is the type of muscular contraction, characterized by increase in tension, without any change, in the length of muscle fibers. Isometric contraction, of ventricular muscle is also called isovolumetric, contraction., , Immediately after atrial systole, the atrioventricular, valves are closed due to increase in ventricular, pressure. Semilunar valves are already closed. Now,, ventricles contract as closed cavities, in such a way, that there is no change in the volume of ventricular, chambers or in the length of muscle fibers. Only the, tension increases in ventricular musculature., Because of increased tension in ventricular, musculature during isometric contraction, the pressure, increases sharply inside the ventricles., First Heart Sound, Closure of atrioventricular valves at the beginning of this, phase produces first heart sound., Significance of Isometric Contraction, During isometric contraction period, the ventricular, pressure increases greatly. When this pressure, , 2. Second Stage or Slow Ejection Period, During this stage, the blood is ejected slowly with much, less force. Duration of this period is 0.09 second., End-systolic Volume, Ventricles are not emptied at the end of ejection period, and some amount of blood remains in each ventricle., Amount of blood remaining in ventricles at the end of, ejection period (i.e. at the end of systole) is called end, systolic volume. It is 60 to 80 mL per ventricle., Measurement of end-diastolic volume, Endsystolic volume is measured by radionuclide angio, cardiography (multigated acquisition – MUGA scan), and echocardiography. It is also measured by cardiac, catheterization, computed tomography (CT) scan and, magnetic resonance imaging (MRI) (Chapter 109)., Ejection Fraction, Ejection fraction refers to the fraction (or portion) of end, diastolic volume (see below) that is ejected out by each, ventricle per beat. From 130 to 150 mL of enddiastolic, volume, 70 mL is ejected out by each ventricle (stroke, volume). Normal ejection fraction is 60% to 65%., Determination of ejection fraction, Ejection fraction (Ef) is the stroke volume divided by, enddiastolic volume expressed in percentage. Stroke, volume (SV) is, enddiastolic volume (EDV) minus end, systolic volume (ESV).
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536 Section 8 t Cardiovascular System, Ejection fraction is calculated as:, Ef, , =, , Where,, Ef, =, SV =, EDV =, ESV =, , SV, EDV, , =, , EDV – ESV, EDV, , Ejection fraction, Stroke volume, Enddiastolic volume, Endsystolic volume., , Significance of determining ejection fraction, Ejection fraction is the measure of left ventricular, function. Clinically, it is considered as an important, index for assessing the ventricular contractility. Ejec, tion fraction decreases in myocardial infarction and, cardiomyopathy., , PROTODIASTOLE, Protodiastole is the first stage of ventricular diastole,, hence the name protodiastole. Duration of this period, is 0.04 second. Due to the ejection of blood, the, pressure in aorta and pulmonary artery increases and, pressure in ventricles drops., When intraventricular pressure becomes less than, the pressure in aorta and pulmonary artery, the semilunar, valves close. Atrioventricular valves are already closed, (see above). No other change occurs in the heart during, this period. Thus, protodiastole indicates only the end of, systole and beginning of diastole., Second Heart Sound, Closure of semilunar valves during this phase produces, second heart sound., ISOMETRIC RELAXATION PERIOD, Isometric relaxation is the type of muscular relaxation,, characterized by decrease in tension without any, change in the length of muscle fibers. Isometric relaxa, tion of ventricular muscle is also called isovolumetric, relaxation., , During isometric relaxation period, once again all the, valves of the heart are closed (Fig. 91.2). Now, both the, ventricles relax as closed cavities without any change, in volume or length of the muscle fiber. Intraventricular, pressure decreases during this period. Duration of, isometric relaxation period is 0.08 second., Significance of Isometric Relaxation, During isometric relaxation period, the ventricular pres, sure decreases greatly. When the ventricular pressure, becomes less than the pressure in the atria, the, , atrioventricular valves open. Thus, the fall in pressure, in the ventricles, caused by isometric relaxation is, responsible for the opening of atrioventricular valves,, resulting in filling of ventricles., RAPID FILLING PHASE, When atrionventricular valves are opened, there is a, sudden rush of blood (which is accumulated in atria, during atrial diastole) from atria into ventricles. So, this, period is called the first rapid filling period. Ventricles, also relax isotonically. About 70% of filling takes place, during this phase, which lasts for 0.11 second., Third Heart Sound, Rushing of blood into ventricles during this phase causes, production of third heart sound., SLOW FILLING PHASE, After the sudden rush of blood, the ventricular filling, becomes slow. Now, it is called the slow filling. It is, also called diastasis. About 20% of filling occurs in this, phase. Duration of slow filling phase is 0.19 second., LAST RAPID FILLING PHASE, Last rapid filling phase occurs because of atrial systole., After slow filling period, the atria contract and push a, small amount of blood into ventricles. About 10% of, ventricular filling takes place during this period. Flow of, additional amount of blood into ventricle due to atrial, systole is called atrial kick., End-diastolic Volume, Enddiastolic volume is the amount of blood remaining, in each ventricle at the end of diastole. It is about 130 to, 150 mL per ventricle., Measurement of end-diastolic volume, Enddiastolic volume is measured by the same methods,, which are used to measure endsystolic volume (see, above)., , INTRA-ATRIAL PRESSURE CHANGES, DURING CARDIAC CYCLE, SIGNIFICANCE, Pressure in the atria is called the intraatrial pressure., Intraatrial pressure is responsible for opening of the, atrioventricular valves and ventricular filling. It is also, the main factor for the development of venous pulse.
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Chapter 91 t Cardiac Cycle 537, , FIGURE 91.2: Events of cardiac cycle, , METHODS OF STUDY, , Pulmonary Capillary Wedge Pressure, , Right atrial pressure is recorded directly by cardiac, catheterization (Chapter 98). Left atrial pressure is, determined indirectly by measuring pulmonary capillary, wedge pressure, which reflects the left atrial pressure, accurately., , Pulmonary capillary wedge pressure is the pressure, exerted in the pulmonary capillary bed after obstructing, the proximal part of pulmonary artery., Pulmonary capillary wedge pressure is measured, by using a balloontipped multilumen cardiac catheter
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538 Section 8 t Cardiovascular System, (SwanGanz catheter). Tip of the catheter is not open, , but a pressure transducer is attached to it., By means of venous puncture, the catheter is, guided through right atrium into right ventricle. From, the right ventricle, it is advanced towards the proximal, portion of pulmonary artery and the balloon is inflated, with air by using a syringe. This occludes the pulmonary, artery. Then, the catheter alone is advanced further into, distal portion of pulmonary artery, leaving the inflated, balloon at the proximal portion. It allows the catheter to, float in a wedge position. Now the pressure existing in, the pulmonary capillary bed ahead of catheter is called, pulmonary capillary wedge pressure (the word wedge, refers to being obstructed)., When the proximal part of pulmonary artery is, obstructed, pressure in the distal part falls rapidly and, after about 10 seconds, it becomes equal to left atrial, pressure. It is because of the absence of any valve, between pulmonary capillary bed and left atrium. So,, the left atrial pressure can be determined by measuring, pulmonary capillary wedge pressure., , TABLE 91.1: Pressure changes during cardiac cycle, Area, , Maximum, pressure, , Minimum, pressure, , Left atrium, , 7 to 8 mm Hg, , 0 to 2 mm Hg, , Right atrium, , 5 to 6 mm Hg, , 0 to 2 mm Hg, , Left ventricle, , 120 mm Hg, , 5 mm Hg, , Right ventricle, , 25 mm Hg, , 2 to 3 mm Hg, , Systemic aorta, , 120 mm Hg, , 80 mm Hg, , 25 mm Hg, , 7 to 8 mm Hg, , Pulmonary artery, , has three positive waves, a, c and v and three negative, waves, x, x1 and y (Fig. 91.3)., ‘a’ Wave, ‘a’ wave is the first positive wave and occurs during, , atrial systole. The pressure rises sharply up to 5 mm Hg, , in right atrium and 7 mm Hg in left atrium. After reaching, the peak, the pressure starts decreasing., ‘x’ Wave, , Maximum and minimum pressures in the left and right, atria are given in Table 91.1., , ‘x’ wave is the first negative wave and appears during, the onset of atrial diastole. Because of relaxation of, atria, the pressure falls. Atrioventricular valves close at, the end of this wave., , INTRA-ATRIAL PRESSURE CURVE, , ‘c’ Wave, , Intraatrial pressure curve is similar to the tracing of, jugular venous pulse, which is known as phlebogram. It, , ‘c’ wave is the second positive wave and this appears, during isometric contraction. Rise in pressure is due to, , MAXIMUM AND MINIMUM PRESSURE IN ATRIA, , FIGURE 91.3: Intraarterial pressure changes during cardiac cycle., a, c, v = Positive waves. x, x1, y = Negative waves.
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Chapter 91 t Cardiac Cycle 539, the closure of atrioventricular valves and the increased, intraventricular pressure., When atrioventricular valves close, there is a, little back flow of blood towards atria. When the, intraventricular pressure increases, there is bulging of, AV valves into the atria. Because of these two factors,, the atrial pressure rises., ‘x1’ Wave, ‘x1’ wave is the second negative wave and appears, during ejection period. During ejection period, the, contraction of ventricular musculature pulls the, atrioventricular ring towards the ventricles. This causes, fall in atrial pressure., , INTRAVENTRICULAR PRESSURE CURVE, Intraventricular pressure curve has seven segments, (Fig. 91.4)., ‘A-B’ Segment, ‘AB’ segment is a positive wave and appears during, atrial systole. Rise in pressure during this period is due, to the entry of a small amount of blood into the ventricles, because of atrial systole. The pressure rises to about 6, to 7 mm Hg in the right ventricle and to about 7 to 8 mm, Hg in the left ventricle., ‘B’ indicates the closure of atrioventricular valves., ‘B-C’ Segment, , ‘v’ Wave, ‘v’ wave is the third positive wave, which is obtained, during atrial diastole. It shows a gradual increase in, atrial pressure due to filling of blood in atria (venous, return)., ‘y’ Wave, ‘y’ wave is the third negative wave and appears after the, opening of AV valves when the blood rushes from atria, into ventricles. So, the pressure in the atria falls., , INTRAVENTRICULAR PRESSURE, CHANGES DURING CARDIAC CYCLE, SIGNIFICANCE, Intraventricular pressure is the pressure developed, inside the ventricles of the heart. It is essential for the, circulation of blood, because the flow of blood through, systemic and pulmonary circulation depends upon the, pressure at which the blood is pumped out of ventricles., Thus, intraventricular pressure is essential for the, circulation of blood., METHODS OF STUDY, Intraventricular pressure is measured by cardiac, catheterization., MAXIMUM AND MINIMUM PRESSURE, IN VENTRICLES, There is some difference in the pressure in right, ventricle and left ventricle. The pressure is always more, in left ventricle than in the right ventricle. Maximum, and minimum pressures in the ventricles are given in, Table 91.1., , ‘BC’ segment appears during isometric contraction., During isometric contraction period, there is a sharp rise, in the intraventricular pressure., ‘C’ denotes the opening of semilunar valves., ‘C-D’ Segment, ‘CD’ segment appears during ejection period. During, ejection period, the pressure in the ventricles rises to the, peak and then falls down. First part of the curve indicates, the maximum ejection and the pressure increases to the, maximum. Second part of the curve represents the slow, ejection phase when the pressure decreases., Maximum pressure rise in right ventricle is about 25, mm Hg and the maximum pressure rise in left ventricle, is about 120 mm Hg, during the peak of this wave., Maximum pressure in the left ventricle is 4 to 5 times, more than that in the right ventricle, because of the thick, wall of the left ventricle., ‘D-E’ Segment, ‘DE’ segment appears during protodiastole. Pressure, decreases slightly due to the starting of ventricular, relaxation., ‘E’ indicates the closure of semilunar valves., ‘E-F’ Segment, ‘EF’ segment is obtained during isometric relaxation., There is a sharp fall in the intraventricular pressure, during this phase. Pressure in the ventricle falls below, the pressure in the atria and this causes the opening of, atrioventricular valves., ‘F’ represents the opening of atrioventricular, valves.
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540 Section 8 t Cardiovascular System, , FIGURE 91.4: Intraventricular pressure changes during cardiac cycle, , ‘F-G’ Segment, , METHOD OF STUDY, , ‘FG’ segment appears during rapid filling phase. In spite, of filling of blood, pressure decreases in the ventricles. It, is because of the relaxation of the ventricles., , Changes in aortic pressure during the cardiac cycle are, recorded by using catheter., , ‘G-A’ Segment, ‘GA’ segment is the last part of intraventricular pressure, curve. It is obtained during slow filling phase. Because, of continuous relaxation of ventricles during slow filling, period, the ventricular pressure decreases further., , AORTIC PRESSURE CHANGES, DURING CARDIAC CYCLE, SIGNIFICANCE, Aortic pressure is the pressure developed in the aorta., It is necessary to maintain the blood flow through the, circulatory system., , MAXIMUM AND MINIMUM, PRESSURE IN AORTA, Pressure in systemic aorta is always higher than, that of pulmonary artery. It is because of the higher, pressure in left ventricle than in the right ventricle., Maximum and minimum pressures in aorta are given, in Table 91.1. Minimum pressure in systemic aorta is, much greater than the minimum pressure in the left, ventricle. It is due to the presence of elastic tissues in, the aorta, which enable the aorta to recoil and maintain, the minimum pressure at a higher level., AORTIC PRESSURE CURVE, During the ejection period of the cardiac cycle, the, pressure in the aorta increases and reaches the peak.
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Chapter 91 t Cardiac Cycle 541, During diastole, it reduces gradually and reaches the, minimum level. At the time of closure of semilunar, valves, an incisura occurs due to back flow of some, blood towards the ventricles (Fig. 91.5)., , VENTRICULAR VOLUME CHANGES, DURING CARDIAC CYCLE, SIGNIFICANCE, Volume of blood in the ventricles is an important factor, to maintain cardiac output and blood circulation., , METHODS OF STUDY, 1. By using Henderson Cardiometer, This study is done only in animals. Cardiometer is a cup, shaped device with an outlet. At the top, it is closed by, means of a rubber diaphragm. A small hole is made in, the diaphragm, through which the ventricles of the animal, are pushed. Cardiometer is connected to a recording, device like Marey tambour (a small stainless steel, capsule covered by rubber membrane) or polygraph, to, record the volume changes (Fig. 99.1)., , FIGURE 91.5: Comprehensive diagram showing ECG, phonocardiogram,, pressure changes and volume changes during cardiac cycle
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542 Section 8 t Cardiovascular System, , FIGURE 91.6: Ventricular volume changes during cardiac cycle, , 2. By Angiography, , Ejection Fraction, , Angiography is the radiographic study of heart and, blood vessels using a radiopaque contrast medium., During angiography, it is possible to measure the, ventricular dimensional area and thickness of ventricular, wall. From the values obtained, the ventricular volume, is calculated., , Ejection fraction (Ef) is the stroke volume divided by, enddiastolic volume, expressed in percentage. See, above for determination and significance of determining, ejection period., , VOLUME OF BLOOD IN RIGHT, AND LEFT VENTRICLES, , VENTRICULAR VOLUME CURVE, Ventricular volume curve recorded by using Henderson, cardiometer has seven segments (Fig. 91.6)., ‘A-B’ Segment, , End-diastolic Volume and End-systolic Volume, Amount of blood is the same in both right and left, ventricles. Maximum volume of blood in each ventricle, after filling (enddiastolic volume) is 130 to 150 mL., Minimum volume of blood left in the ventricles at the, end of ejection period (end of systolic volume) is 60 to, 80 mL., See above for measurement of enddiastolic volume, and endsystolic volume., , ‘AB’ segment wave is because of atrial systole or last, filling phase of ventricles, during which a small amount, of blood enters the ventricles from the atria. It increases, the ventricular volume slightly., ‘B’ indicates the closure of atrioventricular valves., ‘B-C’ Segment, ‘BC’ segment is a positive wave, which is obtained, during isometric contraction. Actually, the ventricular
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Chapter 91 t Cardiac Cycle 543, volume is not altered during isometric contraction., However, the slight upward deflection of this wave is, an artifact. It is because the heart thrusts itself into the, cardiometer during isometric contraction., ‘C’ represents the opening of semilunar valves., ‘C-D’ Segment, ‘CD’ segment occurs during ejection period. Initially,, there is a sharp fall in the ventricular volume. This, occurs during rapid ejection. Later, during slow ejection, period, the blood leaves the ventricles slowly. So the, ventricular volume decreases slowly., ‘D-E’ Segment, ‘DE’ segment part of the ventricular volume curve is, recorded during protodiastole. There is no change in, the ventricular volume during protodiastole., ‘E’ denotes the closure of semilunar valves., , ‘E-F’ Segment, ‘EF’ segment appears during isometric relaxation, period of the cardiac cycle. Actually, the ventricular, volume is not altered during isometric relaxation., However, there is a slight upward deflection in the curve, due to artifact. It is because of the entrance of blood, into coronary artery from aorta during this period. It, increases the pressure within the cardiometer., ‘F’ indicates the opening of atrioventricular valves., ‘F-G’ Segment, ‘FG’ segment appears during rapid filling phase. Rapid, rise in ventricular volume is due to sudden rush of blood, after the opening of atrioventricular valves., ‘G-A’ Segment, ‘GA’ segment is recorded during slow filling phase. Ven, tricular volume increases slowly because of slow filling.
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Chapter, , Heart Sounds, , 92, , INTRODUCTION, , , , DIFFERENT HEART SOUNDS, IMPORTANCE OF HEART SOUNDS, , DESCRIPTION OF DIFFERENT HEART SOUNDS, , , , , , FIRST HEART SOUND, SECOND HEART SOUND, THIRD HEART SOUND, FOURTH HEART SOUND, , TRIPLE AND QUADRUPLE HEART SOUNDS, , , , TRIPLE HEART SOUND OR GALLOP RHYTHM, QUADRUPLE HEART SOUND, , METHODS OF STUDY OF HEART SOUNDS, , , , , BY STETHOSCOPE, BY MICROPHONE, BY PHONOCARDIOGRAM, , INTRODUCTION, Heart sounds are the sounds produced by mechanical, activities of heart during each cardiac cycle., Heart sounds are produced by:, 1. Flow of blood through cardiac chambers, 2. Contraction of cardiac muscle, 3. Closure of valves of the heart., Heart sounds are heard by placing the ear over the, chest or by using a stethoscope or microphone. These, sounds are also recorded graphically., DIFFERENT HEART SOUNDS, Four heart sounds are produced during each cardiac, cycle:, 1. First heart sound, 2. Second heart sound, 3. Third heart sound, 4. Fourth heart sound., First and second heart sounds are called classical, heart sounds and are heard by using the stethoscope., , These two sounds are more prominent and resemble, the spoken words ‘LUB, (or LUBB) and ‘DUBB’ (or, DUP), respectively., Third heart sound is a mild sound and it is not heard, by using stethoscope in normal conditions. But it can, be heard by using a microphone. Fourth heart sound is, an inaudible sound. It becomes audible in pathological, conditions only. This sound is studied only by graphic, registration, i.e. the phonocardiogram., IMPORTANCE OF HEART SOUNDS, Study of heart sounds has important diagnostic value in, clinical practice because alteration in the heart sounds, indicates cardiac diseases involving valves of the, heart., , DESCRIPTION OF HEART SOUNDS, FIRST HEART SOUND, First heart sound is produced during isometric contraction, period and earlier part of ejection period (Table 92.1).
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Chapter 92 t Heart Sounds 545, TABLE 92.1: Heart sounds, Features, , First heart sound, , Second heart sound, , Third heart sound, , Fourth heart sound, , Occurs during, , Isometric contraction, period and part of, ejection period, , Protodiastole and part, of isometric relaxation, , Rapid filling phase, , Atrial systole, , Characteristics, , Long, soft and low, pitched, Resembles the word, ‘LUBB’, , Short, sharp and high, pitched, Resembles the word, ‘DUP’, , Low pitched, , Inaudible sound, , Cause, , Closure of, atrioventricular valves, , Closure of semilunar, valves, , Rushing of blood, into ventricle, , Contraction of atrial, musculature, , Duration (sec), , 0.10 to 0.17, , 0.10 to 0.14, , 0.07 to 0.10, , 0.02 to 0.04, , 50, , 1 to 6, , 1 to 4, , Between ‘T’ wave, and ‘P’ wave, , Between ‘P’ wave, and ‘Q’ wave, , 1 to 4, , 1 to 2, , Frequency (cycles per sec) 25 to 45, Relation with ECG, , Coincides with peak of, ‘R’ wave, , Precedes or appears, 0.09 second after, peak of ‘T’ wave, , Number of vibrations in, phonocardiogram, , 9 to 13, , 4 to 6, , Causes, , Applied Physiology, , Major cause for first heart sound is the sudden and, synchronous (simultaneous) closure of atrioventricular, valves. However, some other factors are also involved., Four types of factors are responsible for the production, of the first heart sound., , 1. Reduplication of first heart sound, , 1. Valvular factor, Synchronous closure of atrioventricular valves set, up the vibrations in the valvular leaflets and chordae, tendineae. These vibrations are mainly responsible for, the production of the first heart sound., 2. Vascular factor, Rush of blood from the ventricles into aorta and, , pulmonary artery during ejection period is also, responsible for the production of the first heart sound., 3. Muscular factor, Myocardial tension and the contraction of ventricular, , muscle during isometric contraction and the ejection, periods also add to the production of the first heart sound., 4. Atrial factor, Vibrations produced by the atrial systole also play a, role in the production of the first heart sound., Characteristics, First heart sound is a long, soft and low-pitched sound., It resembles the spoken word ‘LUBB’. The duration of, this sound is 0.10 to 0.17 second. Its frequency is 25 to, 45 cycles/second., , Reduplication means splitting of the heart sound. First, heart sound is split when the atrioventricular valves, do not close simultaneously (asynchronous closure)., Splitting of first heart sound in normal conditions, (physiological splitting) is rare. Pathological splitting, of first heart sound occurs in stenosis of atrioventricular, valves and atrial septal defect., 2. Soft first heart sound, Heart sound becomes soft when the intensity of sound, decreases. A soft first heart sound is heard in low blood, pressure, severe heart failure, myocardial infarction and, myxedema., 3. Loud or accentuated first heart sound, First heart sound becomes louder or accentuated, (becoming prominent) in conditions like mitral stenosis,, Wolff-Parkinson-White syndrome and acute rheumatic, fever. It is loud in patients with thin chest wall also., 4. Cannon sound, Cannon sound refers to the loud first heart sound that is, heard intermittently. It is heard in ventricular tachycardia, and complete atrioventricular block., First Heart Sound and ECG, First heart sound coincides with peak of ‘R’ wave in, ECG.
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546 Section 8 t Cardiovascular System, SECOND HEART SOUND, Second heart sound is produced at the end of, protodiastolic period., , Pulmonary valve produces loud sound during pulmonary, hypertension., 3. Soft second heart sound, , Cause, , Second heart sound becomes soft in heart failure., , Second heart sound is produced due to the sudden and, synchronous closure of the semilunar valves., , Second Heart Sound and ECG, , Characteristics, Second heart sound is a short, sharp and high-pitched, sound. It resembles the spoken word ‘DUBB’ (or DUP)., Duration of second heart sound is 0.10 to 0.14 second., Its frequency is 50 cycles/second., Applied Physiology, 1. Reduplication of second heart sound, Splitting of second heart sound occurs due to, asynchronous closure of semilunar valves. It may occur, both in physiological and pathological conditions., Physiological splitting: It occurs during deep inspiration., Normally, aortic valve closes prior to the closure of, pulmonary valve. Interval between the two valves widens, during inspiration and narrows during expiration., Increased negative intrathoracic pressure during, deep inspiration increases lung expansion and venous, return into right atrium. However, the venous return, from lungs to left atrium is reduced during this condition., Because of increased venous return in right atrium and, subsequent increase in blood volume in right ventricle,, pulmonary valve is kept open for slightly longer time than, the aortic valve. So, the pulmonary valve closes little, later than the aortic valve causing splitting of second, heart sound., Pathological splitting: The splitting of second heart, sound occurs during pulmonary stenosis, right bundle, branch block and right ventricular hypertrophy., Reverse splitting: It is the splitting of second heart, sound, in which aortic valve closes after the closure, of pulmonary valve. It is due to the delay in emptying, of left ventricle. It is also called paradoxical splitting, (paradoxical = contradictory or opposite). Reverse, splitting is common in left bundle-branch block, aortic, stenosis and left ventricular hypertrophy., 2. Loud or accentuated second heart sound, Loud or accentuated second heart sound is produced, by the closure of either aortic valve or pulmonary valve., Aortic valve produces loud sound during systemic, hypertension and coarctation (narrowing) of aorta., , Second heart sound coincides with the ‘T’ wave in, ECG. Sometimes, it may precede the ‘T’ wave or it may, commence after the peak of ‘T’ wave., THIRD HEART SOUND, Third heart sound is a low-pitched sound that is produced, during rapid filling period of the cardiac cycle. It is also, called ventricular gallop or protodiastolic gallop, as it is, produced during earlier part of diastole., Usually, the third heart sound is inaudible by, stethoscope and it can be heard only by using, microphone., Causes, Third heart sound is produced by the rushing of blood, into ventricles and vibrations set up in the ventricular, wall during rapid filling phase. It may also be due to, vibrations set up in chordae tendineae., Characteristics, Third heart sound is a short and low-pitched sound., Duration of this sound is 0.07 to 0.10 second. Its, frequency is 1 to 6 cycles/second., Conditions when Third Heart Sound, becomes Audible by Stethoscope, Third heart sound can be heard by stethoscope in, children and athletes. Pathological conditions when, third heart sound becomes loud and audible by, stethoscope are aortic regurgitation, cardiac failure and, cardiomyopathy with dilated ventricles., When third heart sound is heard by stethoscope,, the condition is called triple heart sound (see below)., Third heart sound is usually heard best with the bell of, stethoscope placed at the apex beat area, when the, patient is in left lateral decubitus (lying on left side), position., Third Heart Sound and ECG, Third heart sound appears between ‘T’ and ‘P’ waves, of ECG.
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Chapter 92 t Heart Sounds 547, FOURTH HEART SOUND, Normally, the fourth heart sound is an inaudible sound., It becomes audible only in pathological conditions. It, is studied only by graphical recording, i.e. by phonocardiography. This sound is produced during atrial, systole (late diastole) and it is considered as the, physiologic atrial sound. It is also called atrial gallop or, , second heart sounds. It is also called gallop rhythm,, since it resembles the sound of a horse’s gallop. Usually,, it is indicative of serious cardiovascular disease., Conditions when Triple Heart, Sound is Produced, , presystolic gallop., , Triple heart sound is produced in conditions like, myocardial infarction and severe hypertension., , Causes, , QUADRUPLE HEART SOUND, , Fourth heart sound is produced by contraction of, atrial musculature and vibrations are set up in atrial, musculature, flaps of the atrioventricular valves, during systole. It is also due to the vibrations set up, in the ventricular myocardium because of ventricular, distention during atrial systole., Characteristics, Fourth heart sound is a short and low-pitched sound., Duration of this sound is 0.02 to 0.04 second. Its, frequency is 1 to 4 cycles/second., Conditions when Fourth Heart Sound, becomes Audible, Fourth heart sound becomes audible by stethoscope, when the ventricles become stiff. Ventricular stiffness, occurs in conditions like ventricular hypertrophy, long, standing hypertension and aortic stenosis. To overcome, the ventricular stiffness, the atria contract forcefully,, producing audible fourth heart sound., When fourth heart sound is heard by stethoscope,, the condition is called triple heart sound (see below). It, is usually heard best with the bell of stethoscope placed, at the apex beat area, when the patient is in supine or, left semilateral position., Fourth Heart Sound and ECG, , Quadruple heart sound is an abnormal rhythm of heart,, characterized by four clear heart sounds during each, heart beat. It is also called quadruple rhythm. It is due, to third and fourth heart sounds that are heard besides, first and second heart sounds. It is also called quadruple, gallop., , Quadruple heart sound is also indicative of serious, cardiovascular disease., Conditions when Quadruple Heart, Sound is Produced, Quadruple heart sound is produced in patients with, congestive heart failure., Summation Gallop, Whenever there is tachycardia in patients with, quadruple heart sound, the third and fourth heart, sounds merge together and give rise to a single, sound. This sound is called summation gallop and it, resembles gallop rhythm., , METHODS OF STUDY, OF HEART SOUNDS, Heart sounds are studied by three methods:, 1. By using stethoscope, 2. By using microphone, 3. By using phonocardiogram., , Fourth heart sound coincides with the interval between, the end of ‘P’ wave and the onset of ‘Q’ wave., , BY STETHOSCOPE, , TRIPLE AND QUADRUPLE, HEART SOUNDS, , First and second heart sounds are heard on the, auscultation areas, by using the stethoscope. The chest, piece of the stethoscope is placed over four areas on, the chest, which are called auscultation areas., , TRIPLE HEART SOUND, OR GALLOP RHYTHM, , Auscultation Areas, , Triple heart sound or triple rhythm is an abnormal, rhythm of heart, characterized by three clear heart, sounds during each heart beat. It is due to an abnormal, third or fourth heart sound that is heard besides first and, , i. Mitral area (Bicuspid area), Mitral area is in the left 5th intercostal space, about 10, cm away from the midline (midclavicular line). Sound, produced by the closure of mitral valve (first heart
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548 Section 8 t Cardiovascular System, sound) is transmitted well into this area. It is also called, apex beat area because apex beat is felt in this area., Apex beat, Apex beat is the thrust of the apex of ventricles, against, the chest wall during systole., ii. Tricuspid area, Tricuspid area is on the xiphoid process. Sound, produced by the closure of tricuspid valve (first heart, sound) is transmitted well into this area., iii. Pulmonary area, Pulmonary area is on the left 2nd intercostal space,, close to sternum. Sound produced by the closure of, pulmonary valve (second heart sound) is heard well on, this area., iv. Aortic area, Aortic area is over the right 2nd intercostal space,, close to the sternum. On this area, the sound produced, by the closure of aortic valve (second heart sound) is, heard well., First heart sound is best heard in mitral and tricuspid, areas. However, it is heard in other areas also but the, intensity is less. Similarly, the second heart sound is, best heard in pulmonary and aortic areas. It is also, heard in other areas with less intensity., BY MICROPHONE, A highly sensitive microphone is placed over the chest., The heart sounds are amplified by means of an amplifier, and heard by using a loudspeaker. First, second and, third heart sounds are heard by this method., , BY PHONOCARDIOGRAM, Phonocardiography is the technique used to record the, heart sounds. Phonocardiogram is the graphical record, of heart sounds. It is done by placing an electronic sound, transducer over the chest. This transducer is connected, to a recording device like polygraph. All the four heart, sounds can be recorded in phonocardiogram. It helps to, analyze the frequency of the sound waves., Appearance of Heart Sounds, in Phonocardiogram, In phonocardiogram, the heart sounds are recorded in, the following manner (Fig. 91.6)., First heart sound, First heart sound is recorded as single group of waves., The waves are of small amplitude to start with. Later,, the amplitude rapidly rises and falls to form crescendo, and diminuendo series of waves. About 9 to 13 waves, appear., Second heart sound, Second heart sound appears as single group of waves,, which have same amplitude. About 4 to 6 waves are, recorded., Third heart sound, Third heart sound is found in phonocardiogram with only, 1 to 4 waves grouped together., Fourth heart sound, Mostly, the fourth heart sound merges with first heart, sound. If it appears as separate form, it has 1 to 2 waves, with very low amplitude.
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Chapter, , Cardiac Murmur, , 93, , INTRODUCTION, , , CAUSES OF MURMUR, , CLASSIFICATION OF MURMUR, , , , , SYSTOLIC MURMUR, DIASTOLIC MURMUR, CONTINUOUS MURMUR, , INTRODUCTION, Cardiac murmur is the abnormal or unusual heart sound., It is also called abnormal heart sound or cardiac bruit., Cardiac murmur is heard by stethoscope, along with, normal heart sounds., Cardiac murmur is heard by placing chest piece of, stethoscope over the auscultatory areas. Murmur due, to disease of a particular valve is heard well over the, auscultatory area of that valve. Sometimes, the murmur, is felt by palpation as ‘thrills’. In some patients, murmur, is heard without any aid, even at a distance of few feet, away from the patient., , in streamline through the heart and blood vessels., However, during abnormal conditions like valvular, diseases, the blood flow becomes turbulent. It, produces the cardiac murmur., Murmur is produced because of valvular diseases,, septal defects and vascular defects (Table 93.1)., Valvular Diseases, Valvular diseases are of two types:, 1. Stenosis, 2. Incompetence., 1. Stenosis, , CAUSES OF MURMUR, Cardiac murmur is produced because of change, in the pattern of blood flow. Normally, blood flows, , Stenosis means narrowing of heart valve. Blood flows, rapidly with turbulence through the narrow orifice of the, valve, resulting in murmur., , TABLE 93.1: Causes for cardiac murmur, Type of murmur, , Causes, , Systolic murmur, , 1. Incompetence of atrioventricular valves, 2. Stenosis of semilunar valves, 3. Anemia, 4. Septal defect, 5. Coarctation of aorta, , Diastolic murmur, , 1. Stenosis of atrioventricular valves, 2. Incompetence of semilunar valves, , Continuous murmur, , 1. Patent ductus arteriosus
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550 Section 8 t Cardiovascular System, 2. Incompetence, , 5. Coarctation of Aorta, , Incompetence refers to weakening of the heart valve., When the valve becomes weak, it cannot close properly., It causes back flow of blood, resulting in turbulence., This disease is also called regurgitation or valvular, , Coarctation of aorta is a congenital disorder, charac, terized by the narrowing of a part of systemic aorta. A, loud murmur is produced during systole and it is heard, in the earlier part of diastole also., , insufficiency., , DIASTOLIC MURMUR, , CLASSIFICATION OF MURMUR, Cardiac murmur is classified into three types:, A. Systolic murmur, B. Diastolic murmur, C. Continuous murmur., SYSTOLIC MURMUR, Systolic murmur is the murmur which is produced during, systole. It is produced in the following conditions:, 1. Incompetence of Atrioventricular Valves, When the atrioventricular valves become weak, these, valves cannot close completely. It causes regurgitation, of blood from ventricles to the atria during ventricular, systole, producing the murmur. It is a harsh blowing, sound with high frequency., 2. Stenosis of Semilunar Valves, During stenosis of aortic valve, the left ventricular, pressure raises up to 300 mm Hg during systole. It causes, a greater turbulence in the blood flow. The vibrations of, this sound can be felt as ‘thrills’ by palpation over lower, neck region and upper chest. In severe conditions, the, sound is heard even a few feet away from the affected, person. It is a harsh and a loud sound., 3. Murmur due to Anemia, A systolic murmur is heard in severe anemia because of, reduced viscosity and accelerated flow of blood., 4. Septal Defect, During interventricular septal defect, blood flows from, left ventricle to right ventricle during systole. It produces, a systolic murmur. Septal defect is a rare disorder., , Diastolic murmur is the murmur that is produced during, diastole. It is produced in the following conditions:, 1. Stenosis of Atrioventricular Valves, When the atrioventricular valves become narrow, the, turbulence of blood flow occurs during diastole, i.e., when blood enters the ventricles from atria. Murmur, due to stenosis of mitral valve is heard better at mitral, area. Murmur due to stenosis of tricuspid valve is, heard best at tricuspid area. It is a weak sound with, low frequency., Sometimes, murmur due to mitral stenosis cannot, be heard by stethoscope, due to low frequency. But it, can be felt as a mild thrill over mitral area of the chest., 2. Incompetence of Semilunar Valves, Murmur is produced during the regurgitation of blood, from aorta into the ventricle, through incompetent, semilunar valve during diastole. It is like a blowing, sound with low frequency., CONTINUOUS MURMUR, Continuous murmur is the murmur that is heard in, conditions such as patent ductus arteriosus., Patent Ductus Arteriosus, Intact ductus arteriosus is called patent ductus, arteriosus (Chapter 114). A continuous murmur is heard, in this condition. However, intensity of the sound is more, during systole and less during diastole. Because of this,, it is also called machinery murmur., It is a harsh blowing sound and is heard best in, the pulmonary area. The murmur is heard 1 year after, birth.
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Electrocardiogram (ECG), , Chapter, , 94, , DEFINITIONS, USES OF ECG, ELECTROCARDIOGRAPHIC GRID, , , , , DURATION, AMPLITUDE, SPEED OF THE PAPER, , ECG LEADS, , , , BIPOLAR LEADS, UNIPOLAR LEADS, , WAVES OF NORMAL ECG, , , , , , ‘P’ WAVE, ‘QRS’ COMPLEX, ‘T’ WAVE, ‘U’ WAVE, , INTERVALS AND SEGMENTS OF ECG, , , , , , ‘P-R’ INTERVAL, ‘Q-T’ INTERVAL, ‘S-T’ SEGMENT, ‘R-R’ INTERVAL, , DEFINITIONS, , Electrocardiogram, , Electrocardiography, , Electrocardiogram (ECG or EKG from electrokardiogram in Dutch) is the record or graphical registration, of electrical activities of the heart, which occur prior to, the onset of mechanical activities. It is the summed, electrical activity of all cardiac muscle fibers recorded, from surface of the body., , Electrocardiography is the technique by which, electrical activities of the heart are studied. The spread, of excitation through myocardium produces local, electrical potential. This low-intensity current flows, through the body, which acts as a volume conductor., This current can be picked up from surface of the body, by using suitable electrodes and recorded in the form, of electrocardiogram. This technique was discovered, by Dutch physiologist, Einthoven Willem, who is, considered the father of electrocardiogram (ECG)., Electrocardiograph, Electrocardiograph is the instrument (machine) by, which electrical activities of the heart are recorded., , USES OF ECG, Electrocardiogram is useful in determining, diagnosing the following:, 1. Heart rate, 2. Heart rhythm, 3. Abnormal electrical conduction, 4. Poor blood flow to heart muscle (ischemia), 5. Heart attack, , and
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552 Section 8 t Cardiovascular System, 6. Coronary artery disease, 7. Hypertrophy of heart chambers., , ELECTROCARDIOGRAPHIC GRID, The paper that is used for recording ECG is called ECG, paper. ECG machine amplifies the electrical signals, produced from the heart and records these signals on a, moving ECG paper., Electrocardiographic grid refers to the markings, (lines) on ECG paper. ECG paper has horizontal and, vertical lines at regular intervals of 1 mm. Every 5th line, (5 mm) is thickened., DURATION, Time duration of different ECG waves is plotted, horizontally on X-axis., On X-axis, 1 mm = 0.04 second, 5 mm = 0.20 second, AMPLITUDE, Amplitude of ECG waves is plotted vertically on Y-axis., On Y-axis, 1 mm = 0.1 mV, 5 mm = 0.5 mV, SPEED OF THE PAPER, Movement of paper through the machine can be, adjusted by two speeds, 25 mm/second and 50 mm/, second. Usually, speed of the paper during recording, is fixed at 25 mm/second. If heart rate is very high,, speed of the paper is changed to 50 mm/second., , record electrocardiogram. Heart is presumed to lie in, the center of Einthoven triangle., Electrical potential generated from the heart appears, simultaneously on the roots of the three limbs, namely, the left arm, right arm and the left leg., Refer next Chapter for Einthoven law., ECG is recorded in 12 leads, which are generally, classified into two categories., I. Bipolar leads, II. Unipolar leads., BIPOLAR LIMB LEADS, Bipolar limb leads are otherwise known as standard, limb leads. Two limbs are connected to obtain these, leads and both the electrodes are active recording, electrodes, i.e. one electrode is positive and the other, one is negative (Fig. 94.1)., Standard limb leads are of three types:, a. Limb lead I, b. Limb lead II, c. Limb lead III., Lead I, Lead I is obtained by connecting right arm and left arm., Right arm is connected to the negative terminal of the, instrument and the left arm is connected to the positive, terminal., Lead II, Lead II is obtained by connecting right arm and left leg., Right arm is connected to the negative terminal of the, instrument and the left leg is connected to the positive, terminal., , ECG LEADS, ECG is recorded by placing series of electrodes on the, surface of the body. These electrodes are called ECG, leads and are connected to the ECG machine., Electrodes are fixed on the limbs. Usually, right arm,, left arm and left leg are chosen. Heart is said to be in, the center of an imaginary equilateral triangle drawn by, connecting the roots of these three limbs. This triangle, is called Einthoven triangle., Einthoven Triangle and Einthoven Law, Einthoven triangle is defined as an equilateral triangle, that is used as a model of standard limb leads used to, , FIGURE 94.1: Position of electrodes for standard limb leads, RA = Right arm, LA = Left arm, LL=Left leg.
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Chapter 94 t Electrocardiogram (ECG) 553, Lead III, Lead III is obtained by connecting left arm and left leg., Left arm is connected to the negative terminal of the, instrument and the left leg is connected to the positive, terminal., UNIPOLAR LEADS, Here, one electrode is active electrode and the other, one is an indifferent electrode. Active electrode is, positive and the indifferent electrode is serving as a, composite negative electrode., , Unipolar leads are of two types:, 1. Unipolar limb leads, 2. Unipolar chest leads., FIGURE 94.2: Position of electrodes for chest leads, (V1 to V6), , 1. Unipolar Limb Leads, Unipolar limb leads are also called augmented limb leads, or augmented voltage leads. Active electrode is connected, to one of the limbs. Indifferent electrode is obtained by, connecting the other two limbs through a resistance., Unipolar limb leads are of three types:, i. aVR lead, ii. aVL lead, iii. aVF lead., i. aVR lead, Active electrode is from right arm. Indifferent electrode, is obtained by connecting left arm and left leg., ii. aVL lead, Active electrode is from left arm. Indifferent electrode is, obtained by connecting right arm and left leg., iii. aVF lead, Active electrode is from left leg (foot). Indifferent electrode, is obtained by connecting the two upper limbs., , V3 : In between V2 and V4, V4 : Over left 5th intercostal space on the mid, clavicular line, V5 : Over left 5th intercostal space on the anterior, axillary line, V6 : Over left 5th intercostal space on the mid, axillary line., , WAVES OF NORMAL ECG, Normal ECG consists of waves, complexes, intervals, and segments. Waves of ECG recorded by limb, lead II are considered as the typical waves. Normal, electrocardiogram has the following waves, namely P,, Q, R, S and T (Table 94.1 and Fig. 94.3). Einthoven, had named the waves of ECG starting from the middle, of the English alphabets (P) instead of starting from the, beginning (A)., Major Complexes in ECG, , 2. Unipolar Chest Leads, Chest leads are also called ‘V’ leads or precardial chest, leads. Indifferent electrode is obtained by connecting the, three limbs, viz. left arm, left leg and right arm, through, a resistance of 5000 ohms. Active electrode is placed, on six points over the chest (Fig. 94.2). This electrode, is known as the chest electrode and the six points over, the chest are called V1, V2, V3, V4, V5 and V6. V indicates, vector, which shows the direction of current flow., Position of chest leads:, V1 : Over 4th intercostal space near right sternal, margin, V2 : Over 4th intercostal space near left sternal, margin, , 1., 2., 3., 4., , ‘P’ wave, the atrial complex, ‘QRS’ complex, the initial ventricular complex, ‘T’ wave, the final ventricular complex, ‘QRST’, the ventricular complex., , ‘P’ WAVE, ‘P’ wave is a positive wave and the first wave in ECG. It, is also called atrial complex., Cause, ‘P’ wave is produced due to the depolarization of atrial, musculature. Depolarization spreads from SA node to, all parts of atrial musculature. Atrial repolarization is not
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554 Section 8 t Cardiovascular System, TABLE 94.1: Waves of normal ECG, Wave/Segment, , From – To, , Cause, , Duration (second), , Amplitude (mV), , P wave, , –, , Atrial depolarization, , 0.1, , 0.1 to 0.12, , QRS complex, , Onset of Q wave to the, end of S wave, , Ventricular depolarization and, atrial repolarization, , 0.08 to 0.10, , Q = 0.1 to 0.2, R=l, S = 0.4, , T wave, , –, , Ventricular repolarization, , 0.2, , 0.3, , P-R interval, , Onset of P wave to onset Atrial depolarization and, of Q wave, conduction through AV node, , 0.18 (0.12 to 0.2), , –, , Q-T interval, , Onset of Q wave and, end of T wave, , Ventricular depolarization and, ventricular repolarization, , 0.4 to 0.42, , –, , S-T segment, , End of S wave and onset, of T wave, , Isoelectric, , 0.08, , –, , recorded as a separate wave in ECG because it merges, with ventricular repolarization (QRS complex)., , ‘QRS’ COMPLEX, , Normal duration of ‘P’ wave is 0.1 second., , ‘QRS’ complex is also called the initial ventricular, complex. ‘Q’ wave is a small negative wave. It is continued as the tall ‘R’ wave, which is a positive wave. ‘R’, wave is followed by a small negative wave, the ‘S’ wave., , Amplitude, , Cause, , Normal amplitude of ‘P’ wave is 0.1 to 0.12 mV., , ‘QRS’ complex is due to depolarization of ventricular, musculature. ‘Q’ wave is due to the depolarization of, , Morphology, , basal portion of interventricular septum. ‘R’ wave is due, to the depolarization of apical portion of interventricular, septum and apical portion of ventricular muscle. ‘S’, wave is due to the depolarization of basal portion of, ventricular muscle near the atrioventricular ring., , Duration, , ‘P’ wave is normally positive (upright) in leads I, II,, aVF, V4, V5 and V6. It is normally negative (inverted) in, aVR. It is variable in the remaining leads, i.e. it may be, positive, negative, biphasic or flat (Fig. 94.4)., Clinical Significance, Variation in the duration, amplitude and morphology, of ‘P’ wave helps in the diagnosis of several cardiac, problems such as:, 1. Right atrial hypertrophy: ‘P’ wave is tall (more than, 2.5 mm) in lead II. It is usually pointed, 2. Left atrial dilatation or hypertrophy: It is tall and, broad based or M shaped, 3. Atrial extrasystole: Small and shapeless ‘P’ wave,, followed by a small compensatory pause, 4. Hyperkalemia: ‘P’ wave is absent or small, 5. Atrial fibrillation: ‘P’ wave is absent, 6. Middle AV nodal rhythm: ‘P’ wave is absent, 7. Sinoatrial block: ‘P’ wave is inverted or absent, 8. Atrial paroxysmal tachycardia: ‘P’ wave is inverted, 9. Lower AV nodal rhythm: ‘P’ wave appears after QRS, complex., , Duration, Normal duration of ‘QRS’ complex is between 0.08 and, 0.10 second., Amplitude, Amplitude of ‘Q’ wave = 0.1 to 0.2 mV., Amplitude of ‘R’ wave = 1 mV., Amplitude of ‘S’ wave = 0.4 mV., Morphology, ‘Q’ wave is normally small with amplitude of 4 mm or, less. It is less than 25% of amplitude of ‘R’ wave in, leads I, II, aVL, V5 and V6. In the remaining leads, its, amplitude is < 0.2 mm., From chest leads V1 to V6, ‘R’ wave becomes, gradually larger. It is smaller in V6 than V5. ‘S’ wave is, large in V1 and larger in V2. It gradually becomes smaller, from V3 to V6.
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Chapter 94 t Electrocardiogram (ECG) 555, , FIGURE 94.3: Waves of normal ECG
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556 Section 8 t Cardiovascular System, Clinical Significance, Variation in duration, amplitude and morphology of, ‘T’ wave helps in the diagnosis of several cardiac, problems such as:, 1. Acute myocardial ischemia: Hyperacute ‘T’ wave, develops. Hyperacute ‘T’ wave refers to a tall and, broad-based ‘T’ wave, with slight asymmetry., 2. Old age, hyperventilation, anxiety, myocardial infarc, tion, left ventricular hypertrophy and pericarditis: ‘T’, wave is small, flat or inverted, 3. Hypokalemia: ‘T’ wave is small, flat or inverted, 4. Hyperkalemia: ‘T’ wave is tall and tented., ‘U’ WAVE, ‘U’ wave is not always seen. It is also an insignificant, wave in ECG. It is supposed to be due to repolarization, of papillary muscle., Clinical Significance, , FIGURE 94.4: 12-lead ECG, (Courtesy: Dr Atul Ruthra), , Clinical Significance, Variation in the duration, amplitude and morphology, of ‘QRS’ complex helps in the diagnosis of several, cardiac problems such as:, 1. Bundle branch block: QRS is prolonged or deformed, 2. Hyperkalemia: QRS is prolonged., , Appearance of ‘U’ wave in ECG indicates some clinical, conditions such as:, 1. Hypercalcemia, thyrotoxicosis and hypokalemia: ‘U’, wave appears. It is very prominent in hypokalemia., 2. Myocardial ischemia: Inverted ‘U’ wave appears., , INTERVALS AND SEGMENTS OF ECG, ‘P-R’ INTERVAL, , Cause, , ‘P-R’ interval is the interval between the onset of ‘P’, wave and onset of ‘Q’ wave., ‘P-R’ interval signifies the atrial depolarization and, conduction of impulses through AV node. It shows the, duration of conduction of the impulses from the SA node, to ventricles through atrial muscle and AV node., ‘P’ wave represents the atrial depolarization. Short, isoelectric (zero voltage) period after the end of ‘P’, wave represents the time taken for the passage of, depolarization within AV node., , ‘T’ wave is due to the repolarization of ventricular, , Duration, , ‘T’ WAVE, ‘T’ wave is the final ventricular complex and is a positive, wave., , musculature., , Duration, Normal duration of ‘T’ wave is 0.2 second., Amplitude, Normal amplitude of ‘T’ wave is 0.3 mV., Morphology, ‘T’ wave is normally positive in leads I, II and V5 and V6., It is normally inverted in lead aVR. It is variable in the, other leads, i.e. it is positive, negative or flat., , Normal duration of ‘P-R interval’ is 0.18 second and, varies between 0.12 and 0.2 second. If it is more than, 0.2 second, it signifies the delay in the conduction of, impulse from SA node to the ventricles. Usually, the, delay occurs in the AV node. So it is called the AV nodal, delay., , Clinical Significance, Variation in the duration of ‘P-R’ intervals helps in the, diagnosis of several cardiac problems such as:, 1. It is prolonged in bradycardia and first degree heart, block
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Chapter 94 t Electrocardiogram (ECG) 557, 2. It is shortened in tachycardia, Wolf-ParkinsonWhite syndrome, Lown-Ganong-Levine syndrome,, Duchenne muscular dystrophy and type II glycogen, storage disease., ‘Q-T’ INTERVAL, ‘Q-T’ interval is the interval between the onset of ‘Q’, wave and the end of ‘T’ wave., ‘Q-T’ interval indicates the ventricular depolarization, and ventricular repolarization, i.e. it signifies the, electrical activity in ventricles., Duration, Normal duration of Q-T interval is between 0.4 and 0.42, second., Clinical Significance, 1. ‘Q-T’ interval is prolonged in long ‘Q-T’ syndrome,, myocardial infarction, myocarditis, hypocalcemia, and hypothyroidism, 2. ‘Q-T’ interval is shortened in short ‘Q-T’ syndrome, and hypercalcemia., , 3. ‘S-T’ segment is prolonged in hypocalcemia, 4. ‘S-T’ segment is shortened in hypercalcemia., ‘R-R’ INTERVAL, ‘R-R’ interval is the time interval between two consecutive, ‘R’ waves., Significance, ‘R-R’ interval signifies the duration of one cardiac, cycle., Duration, Normal duration of ‘R-R’ interval is 0.8 second., Significance of Measuring ‘R-R’ Interval, Measurement of ‘R-R’ interval helps to calculate:, 1. Heart rate, 2. Heart rate variability., 1. Heart Rate, Heart rate is calculated by measuring the number of ‘R’, waves per unit time., , ‘S-T’ SEGMENT, , Calculation of heart rate, , ‘S-T’ segment is the time interval between the end of, ‘S’ wave and the onset of ‘T’ wave. It is an isoelectric, period., , Time is plotted horizontally (X-axis). On X-axis, interval, between two thick lines is 0.2 sec (see above). Time, duration for 30 thick lines is 6 seconds. Number of ‘R’, waves (QRS complexes) in 6 seconds (30 thick lines), is counted and multiplied by 10 to obtain heart rate. For, the sake of convenience, the ECG paper has special, time marking at every 3 seconds. So it is easy to find the, time duration of 6 seconds., , J Point, The point where ‘S-T’ segment starts is called ‘J’ point., It is the junction between the QRS complex and ‘S-T’, segment., Duration of ‘S-T’ Segment, Normal duration of ‘S-T’ segment is 0.08 second., Clinical Significance, Variation in the duration of ‘S-T’ segment and its, deviation from isoelectric base indicates the pathological conditions such as:, 1. Elevation of ‘S-T’ segment occurs in anterior or, inferior myocardial infarction, left bundle branch, block and acute pericarditis. In athletes, ‘S-T’, segment is usually elevated, 2. Depression of ‘S-T’ segment occurs in acute myocardial ischemia, posterior myocardial infarction,, ventricular hypertrophy and hypokalemia, , 2. Heart Rate Variability, Heart rate variability (HRV) refers to the beat-tobeat variations. Under resting conditions, the ECG of, healthy individuals exhibits some periodic variation in, ‘R-R’ intervals. This rhythmic phenomenon is known as, respiratory sinus arrhythmia (RSA), since it fluctuates, with the phases of respiration. ‘R-R’ interval decreases, during inspiration and increases during expiration, (Chapter 96)., Significance of Heart Rate Variability, HRV decreases in many clinical conditions like:, 1. Cardiovascular dysfunctions such as hypertension, 2. Diabetes mellitus, 3. Psychiatric problems such as panic and anxiety.
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Chapter, , Vector, , 95, , INTRODUCTION, INSTANTANEOUS MEAN VECTOR, DEGREE OF INSTANTANEOUS MEAN VECTOR, , , DEGREE OF INSTANTANEOUS MEAN VECTOR AT DIFFERENT LIMB LEADS, , CALCULATED VECTOR OR MEAN QRS VECTOR, , , CALCULATION OF MEAN QRS VECTOR, , VECTORAL ANALYSIS, VECTOR CARDIOGRAM, , INTRODUCTION, Cardiac vector is the direction at which electrical, potential generated in the heart travels at an instant. It, is also called cardiac axis., Vector is represented by an arrow. Arrowhead, shows the direction of electrical potential. Length of the, arrow represents the amplitude (magnitude or voltage), of the potential., , INSTANTANEOUS MEAN VECTOR, Current flows in all directions. Mean direction of, flow of electrical potential at one instance is known, as instantaneous mean vector or instantaneous, summated vector (Fig. 95.1)., For example, when current flows through, interventricular septum from the base of ventricles, towards apex, the electrical potential generated by flow, of current travels in different directions as follows:, 1. Electrical potential travels downwards through, the interventricular septum, towards the apical, part, i.e. from depolarized part of septum towards, non-depolarized (polarized) part of septum. This, potential is strong., 2. Through the inner surface of ventricles, the potential, travels upwards from apical part towards the base., Magnitude of this potential is very weak., , FIGURE 95.1: Instantaneous mean vector when current, flows through interventricular septum of the heart, , 3. Through the outer surface of heart, the electrical, potential travels downwards. It has a higher, magnitude., Though the potential travels in all directions in this, instance, the potential flowing downwards (from base, to apex of the heart) is much greater in magnitude, than the potential flowing in other directions. Thus,, the mean direction of flow of electrical potential in this, instance is downwards. This downward vector is called
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Chapter 95 t Vector 559, instantaneous mean vector or instantaneous summated, vector at this instance., , DEGREE OF INSTANTANEOUS, MEAN VECTOR, While recording electrocardiogram (ECG) in different, limb leads, the degree of vector is altered. Direction of, current flow is always from negative point towards the, positive point. When the electrical potential flows in a, horizontal plane from right side towards left side of the, heart, the degree of vector is zero (Fig. 95.2)., DEGREE OF INSTANTANEOUS MEAN, VECTOR AT DIFFERENT LIMB LEADS, Standard Limb Lead I (Right Arm and Left Arm), In this instance, the electrical potential travels from, right side (negative point) of the heart towards the left, side (positive point) in the horizontal plane. So, the, degree of vector is considered as zero., Standard Limb Lead II (Right Arm and Left Leg), Vector is from above downwards and slightly towards, left, i.e. at 60°., Standard Limb Lead III (Left Arm and Left Leg), Here, vector is from above downwards and slightly, towards right at 120°., Lead Augmented Vector Right (aVR), Vector is from below towards upper part of the heart, and slightly towards right at 210°., , Lead Augmented Vector Front (aVF), Vector is from above downwards at 90°., Lead Augmented Vector Left (aVL), In this, the vector is from below, towards upper part of, the heart and slightly towards left, at –30° or at +330°., , CALCULATED VECTOR OR, MEAN QRS VECTOR, Instantaneous mean vector cannot be determined by the, recording of ECG. But, another vector can be calculated, by measuring the amplitude of QRS complex from the, ECG, recorded in standard limb leads. It is called the, calculated vector or mean QRS vector., It is also called the electrical axis of the heart or, cardiac vector., Calculated cardiac vector is useful in the diagnosis, of heart diseases., CALCULATION OF MEAN QRS VECTOR, Calculation of mean QRS vector depends upon the, fact that if the amplitude of QRS complex is determined, from ECG recorded at any two standard limb leads, the, amplitude of QRS complex in the remaining lead can be, known from the calculation., Amplitude is measured in mm. For determining the, amplitude of QRS complex, first the height of R wave is, measured. From this value, height of negative wave Q, or S (whichever is more) is deducted. The calculation is, based on Einthoven triangle., Einthoven Triangle, Refer previous Chapter for Einthoven triangle., Steps for Calculation of Mean QRS Vector, , FIGURE 95.2: Degree of instantaneous vector, at different leads, , 1. An equilateral triangle is drawn on a plain paper., This triangle represents Einthoven triangle. Each, side of this triangle represents one standard limb, lead., 2. From the midpoint of each side, a perpendicular line, is drawn towards the center. Meeting point of the, perpendicular lines represents center of electrical, activity in the heart (Fig. 95.3)., 3. On each side of triangle, the amplitude of QRS, complex is plotted from midpoint towards the positive, point of the lead. For example, the amplitude of, QRS complex in lead I is 10 mm and in lead II, it is, 16 mm (Fig. 95.4)., 4. In the triangle, upper side represents lead I and in, this lead, the left is positive. So, a 10 mm line is drawn
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560 Section 8 t Cardiovascular System, Amplitude of QRS Complex in Lead III, Amplitude (electrical potential) of QRS complex in lead, III can be calculated by applying Einthoven law., Einthoven law, Einthoven law states that potential differences between, the bipolar leads measured simultaneously will, at, any given moment, have the values II = I + III. That is,, the potential of any wave or complex in lead II of ECG, is equal to the sum of potentials in lead I and lead III., Einthoven law is the modification of Kirchhoff’s law of, voltage., FIGURE 95.3: Einthoven triangle. C = Center of electrical, activity, RA = Right arm, LA = Left arm, LL = Left leg, LI, LII, and LIII = Standard limb leads., , Kirchhoff’s law of voltage, According to Kirchhoff law, the algebraic sum of voltage, rise in a closed circuit is equal to the algebraic sum of, voltage drops., Application of Einthoven law in calculating QRS, complex, , FIGURE 95.4: Calculation of cardiac vector., Arrow in the center indicates the cardiac vector., , 5., 6., , 7., , 8., , on upper side from the midpoint, towards left, (positive). This 10 mm distance along the axis of, lead I is called projected vector for lead I., In the same way, the projected vector for Lead II is, drawn on the right side of the triangle, From the positive end of each projected vector, another perpendicular line is drawn towards interior, of the triangle, Now an arrow is drawn between center of electrical, activity and the meeting point of perpendicular lines, from positive end of projected vectors (Fig. 95.5)., This arrow shows the vector. Arrowhead is drawn, towards positive end, i.e. downwards., Degree and the length of the arrow are measured., Degree denotes the direction of vector and length, denotes the magnitude., , By applying Einthoven law, amplitude (electrical potential) of QRS complex in one lead can be mathematically, calculated, by summing up or subtracting the amplitude, in other two leads, depending upon the potentials of, these leads., For example, amplitude of QRS in lead II = I + III, and the amplitude of QRS in lead III = II – I. Thus,, in this case of Einthoven triangle mentioned above,, amplitude of QRS in lead I is 1 mV and lead II is 1.6, mV. Thus, the amplitude of QRS in lead III is 0.6 mV., It can also be measured from the triangle drawn to, calculate the vector (Fig. 95.5)., , FIGURE 95.5: Determination of vector in Lead I and Lead II
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Chapter 95 t Vector 561, , VECTORAL ANALYSIS, , VECTOR CARDIOGRAM, , Mean QRS vector (cardiac axis) in normal conditions is, at about +59°. It varies between –30° and +110°., When the axis deviates towards the left, i.e. in anticlockwise direction, away from –30°, it is called left axis, deviation. When the axis deviates towards the right, (clockwise direction), away from +110°, it is known as, right axis deviation., , From the recording of the electrocardiogram, only, the calculated vector, i.e. cardiac axis is determined., Instantaneous mean vector cannot be determined by, the electrocardiogram, but it can be determined by, means of vector cardiogram., Vector cardiogram is the simultaneous recording, of electrical potential in different axis across the heart, above, downward and sideward. It is obtained by using, a cathode-ray oscilloscope. The technique is equal to, connecting the tops of all instantaneous mean vectors, in the series of 3 loops. It is done by means of a, sophisticated electronic device along with oscilloscope., Each loop of electronic connection is used to record, different vector cardiogram called P vector cardiogram,, QRS vector cardiogram and T vector cardiogram., , Left axis deviation, Left axis deviation occurs in left ventricular hypertrophy,, left bundle-branch block and posterior wall infarction., Right axis deviation, Right axis deviation occurs due to right ventricular, hypertrophy, right bundle-branch block and anterior wall, infarction.
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Chapter, , Arrhythmia, , 96, , DEFINITION, CLASSIFICATION, NORMOTOPIC ARRHYTHMIA, , , , , SINUS ARRHYTHMIA, SINUS TACHYCARDIA, SINUS BRADYCARDIA, , ECTOPIC ARRHYTHMIA, , , , , , , , HEART BLOCK, EXTRASYSTOLE, PAROXYSMAL TACHYCARDIA, ATRIAL FLUTTER, ATRIAL FIBRILLATION, VENTRICULAR FIBRILLATION, , ABNORMAL PACEMAKER, ARTIFICIAL PACEMAKER, CURRENT OF INJURY, , DEFINITION, Arrhythmia refers to irregular heartbeat or disturbance in, the rhythm of heart. In arrhythmia, heartbeat may be fast, or slow or there may be an extra beat or a missed beat., It occurs in physiological and pathological conditions., , Normotopic arrhythmia is of three types:, 1. Sinus arrhythmia, 2. Sinus tachycardia, 3. Sinus bradycardia., SINUS ARRHYTHMIA, , In arrhythmia, SA node may or may not be the, pacemaker. If SA node is not the pacemaker, any other, part of the heart such as atrial muscle, AV node and, ventricular muscle becomes the pacemaker., Accordingly, arrhythmia is classified into two types:, A. Normotopic arrhythmia, B. Ectopic arrhythmia., , Sinus arrhythmia is a normal rhythmical increase, and decrease in heart rate, in relation to respiration., It is also called respiratory sinus arrhythmia (RSA)., Normal sinus rhythm means the normal heartbeat with, SA node as the pacemaker., Normal heart rate is 72 per minute. However, under, physiological conditions, in a normal healthy person,, heart rate varies according to the phases of respiratory, cycle. Heart rate increases during inspiration and, decreases during expiration., , NORMOTOPIC ARRHYTHMIA, , ECG Changes, , Normotopic arrhythmia is the irregular heartbeat, in, which SA node is the pacemaker., , ECG is normal during sinus arrhythmia. Only the duration, of R-R interval varies rhythmically according to phases, , CLASSIFICATION
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Chapter 96 t Arrhythmia 563, , FIGURE 96.1: ECG in sinus arrhythmia. Normal P-QRS-T., R-R interval is shortened during inspiration and prolonged, during expiration (Courtesy: Dr Atul Ruthra)., , of respiration (Fig. 96.1). It is shortened during inspiration, and prolonged during expiration (Chapter 94)., Cause, Sinus arrhythmia is due to fluctuation in the discharge of, impulses from SA node (Fig. 96.2). During inspiration,, the lungs are inflated and the intrathoracic pressure, decreases. This increases the venous return. Inflation, of lungs stimulates the stretch receptors of lungs, which, send impulses to vasodilator area (cardioinhibitory, center) through afferent fibers of vagus. It leads to, reflex inhibition of vasodilator area and reduction in, , vagal tone. Because of these two factors, heart rate, increases. Simultaneously, increased venous return, initiates Bainbridge reflex that causes increase in heart, rate (Chapter 101)., During expiration, the lungs are deflated and, intrathoracic pressure increases. This decreases the, venous return. During deflation of lungs, the stretch, receptors are not stimulated and vasodilator area is not, inhibited. So, vagal tone increases, resulting in decreased, heart rate. Simultaneously, decreased venous return, abolishes Bainbridge reflex. It also decreases the heart, rate., SINUS TACHYCARDIA, Sinus tachycardia is the increase in discharge of, impulses from SA node, resulting in increase in heart, rate. Discharge of impulses from SA node is very rapid, and the heart rate increases up to 100/minute and, sometimes up to 150/minute., ECG Changes, ECG is normal in sinus tachycardia, except for short R-R, intervals because of increased heart rate (Fig. 96.3)., , FIGURE 96.2: Sinus arrhythmia
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564 Section 8 t Cardiovascular System, Physiological conditions when sinus, bradycardia occurs, 1. Sleep, 2. Athletic heart., FIGURE 96.3: ECG in sinus tachycardia. Normal P-QRS-T., R-R interval is shortened. Heart rate is more than 100/min, (Courtesy: Dr Atul Ruthra)., , Conditions when Sinus Tachycardia Occurs, Sinus tachycardia occurs in physiological as well as, pathological conditions., Physiological conditions when tachycardia occurs, 1., 2., 3., 4., , Exercise, Emotion, High altitude, Pregnancy., , Pathological conditions when tachycardia occurs, 1., 2., 3., 4., 5., 6., 7., , Fever, Anemia, Hyperthyroidism, Hypersecretion of catecholamines, Cardiomyopathy, Valvular heart disease, Hemorrhagic shock., , Features of Sinus Tachycardia, 1., 2., 3., 4., 5., , Palpitations (sensation of feeling the heartbeat), Dizziness, Fainting, Shortness of breath, Chest discomfort (angina)., , SINUS BRADYCARDIA, Sinus bradycardia is the reduction in discharge of, impulses from SA node resulting in decrease in heart, rate. Heart rate is less than 60/minute., , Pathological conditions when sinus, bradycardia occurs, 1., 2., 3., 4., 5., 6., 7., 8., 9., , Disease of SA node, Hypothermia, Hypothyroidism, Heart attack, Congenital heart disease, Degenerative process of aging, Obstructive jaundice, Increased intracranial pressure, Use of certain drugs like beta blockers, channel, blockers, digitalis and other antiarrhythmic drugs, 10. Atherosclerosis. Bradycardia due to atherosclerosis, of carotid artery, at the region of carotid sinus is, called carotid sinus syndrome., Features of Sinus Bradycardia, 1., 2., 3., 4., 5., 6., , Sick sinus syndrome, Fatigue, Weakness, Shortness of breath, Lack of concentration, Difficulty in exercising., , Sick sinus syndrome, Sick sinus syndrome is the common feature of sinus, bradycardia. It is the condition characterized by dizziness and unconsciousness., , ECTOPIC ARRHYTHMIA, Ectopic arrhythmia is the abnormal heartbeat, in which, one of the structures of heart other than SA node, becomes the pacemaker. Impulses produced by these, structures are called ectopic foci., , ECG Changes, ECG shows prolonged waves and prolonged R-R, interval (Fig. 96.4)., Conditions when Sinus Bradycardia Occurs, Sinus bradycardia occurs in both physiological and, pathological conditions. It occurs during sleep. It is, common in athletes due to the cardiovascular reflexes,, in response to increased force of contraction of heart., , FIGURE 96.4: ECG in sinus bradycardia. Normal P-QRS-T., R-R interval is prolonged. Heart rate is less than 60/min., (Courtesy: Dr Atul Ruthra).
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Chapter 96 t Arrhythmia 565, Subtypes of Ectopic Arrhythmia, , HEART BLOCK, , Ectopic arrhythmia is further divided into two subtypes:, 1. Homotopic arrhythmia, in which the impulses for, heartbeat arise from any part of conductive system, 2. Heterotopic arrhythmia, in which the impulses arise, from the musculature of heart other than conductive, system., , Heart block is the blockage of impulses generated, by SA node in the conductive system. Because of, the blockage, the impulses cannot reach the cardiac, musculature, resulting in ectopic arrhythmia. Based on, the area affected, the heart block is classified into two, types (Fig. 96.5):, 1. Sinoatrial block, 2. Atrioventricular block., , Different Ectopic Arrhythmia, 1., 2., 3., 4., 5., 6., , Heart block, Extrasystole, Paroxysmal tachycardia, Atrial flutter, Atrial fibrillation, Ventricular fibrillation., , Sinoatrial Block – AV Nodal Rhythm, Sinoatrial block is the failure of impulse transmission, from SA node to AV node. It is also called sinus, block. During sinoatrial block, heart stops beating., Immediately, AV node takes over the pacemaker, function and produces the impulses. This leads to AV, nodal (atrioventricular) rhythm., , FIGURE 96.5: Classification of arrhythmia. AV = Atrioventricular.
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566 Section 8 t Cardiovascular System, Sinoatrial block is due to the defect in internodal, fibers and it occurs suddenly. Initially, the heart stops, for a while. Then after few seconds, the AV node, becomes the pacemaker and the heart starts beating, with decreased rate of 40 to 60/minute., Impulses may be discharged from any part of AV, node, viz., 1. In upper nodal rhythm, the impulses are discharged, from the upper part of AV node. In this rhythm, the P, wave of ECG is inverted. QRS complex and T wave, are normal, 2. In middle nodal rhythm, the impulses are by the, middle part of AV node. Here, all the chambers of, the heart contract simultaneously. P wave of ECG is, absent as it merges with QRS complex, 3. In lower nodal rhythm, the impulses are produced by, the lower part of AV node. In this condition, ventricular, contraction occurs prior to atrial contraction as the, impulses reach the ventricles prior to the atria. In, ECG, QRS complex appears prior to P wave and, R-P interval is obtained instead of P-R interval. It is, called reversed heart block., Atrioventricular Block, Atrioventricular block is the heart block in which the, impulses are not transmitted from atria (from AV node), to ventricles because of defective conductive system., Atrioventricular block is of two categories:, 1. Incomplete heart block, 2. Complete heart block., , ii. Second degree heart block, Second degree heart block is the type of heart block in, which some of the impulses produced by SA node fail, to reach the ventricles. It is also called the partial heart, block. When some of the impulses from SA node fail to, reach the ventricles, one ventricular contraction occurs, for every 2, 3 or 4 atrial contractions, i.e. 2 : 1, 3 : 1 or 4, : 1. In ECG, the ventricular complex (QRST) is missing, accordingly., During frequent development of second degree, heart block, bradycardia occurs., iii. Wenckebach phenomenon or syndrome, Wenckebach phenomenon is a type of heart block, characterized by progressive increase in AV nodal, delay, resulting in missing of one beat. Afterwards, the, conduction of impulse is normal or slightly delayed. In, ECG, the progressive lengthening of P-R interval is, noticed till QRST complex disappears., iv. Bundle branch block, Bundle branch block (BBB) is the heart block that, occurs during dysfunction of right or left branch of, bundle of His. During this type of block, the impulse, from atria reaches unaffected ventricle first. Then, from, here, the impulse travels to the affected side. So, ECG, shows normal ventricular rate, but the QRS complex is, prolonged or deformed., 2. Complete Heart Block, (Third degree heart block), , Incomplete heart block is the condition in which the, transmission of impulses from atria to ventricles is, slowed down and not blocked completely. Impulses, reach ventricles late., Incomplete heart block is of four types:, i. First degree heart block, ii. Second degree heart block, iii. Wenckebach phenomenon, iv. Bundle branch block., , Complete heart block is the condition in which the, impulses produced by SA node cannot reach the, ventricles. It is also called complete atrioventricular, block or third degree heart block. Because of this, the, ventricles beat in their own rhythm, independent of atrial, beat. It is called idioventricular rhythm., Complete heart block occurs due to any one of the, following causes:, i. Disease of AV node, which leads to AV nodal, block, ii. Defective conductive system below the level of, AV node, causing infranodal block., , i. First degree heart block, , i. AV nodal block, , First degree heart block is the heart block in which, the conduction of impulses through AV node is very, slow, i.e. the AV nodal delay is longer. It is also called, delayed conduction. In ECG, the P-R interval is very, much prolonged and is more than 0.2 second., First degree heart block is common in young adults, and trained athletes. It is also caused by rheumatic fever, and some drugs. It does not produce any symptom., , In this type of block, a part of AV node is defective, and the unaffected part becomes the pacemaker., Rhythmicity of AV node is about 45 to 60/minute., , 1. Incomplete Heart Block, , ii. Infranodal block, Infranodal block is the heart block in which the impulses, from SA node are blocked in the branches of bundle of, His (below the level of AV node). In this condition, the
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Chapter 96 t Arrhythmia 567, distal part of the conductive system (i.e. the Purkinje, fibers) becomes the pacemaker. The rhythmicity of, Purkinje fibers is about 35/minute. Sometimes, a part, of ventricular musculature becomes the pacemaker, and the ventricular rate in such conditions is about 20/, minute., Third degree heart block is the serious one since it, decreases the pumping action of the heart. Very often,, it results in Stokes-Adams syndrome. It may also cause, heart failure., , Parts of the heart which give origin for ectopic foci, are AV node, bundle of His, atrial musculature and, ventricular musculature., Accordingly, extrasystole is divided into three, types:, 1. Atrial extrasystole, 2. Nodal extrasystole, 3. Ventricular extrasystole., , Stokes-Adams syndrome, , Atrial extrasystole is the premature contraction, produced by a stimulus arising from atrial muscle. In, this condition, an extra P wave appears immediately, after the regular T wave. P wave is small and shapeless., The P-R interval of this beat is short., , Stokes-Adams syndrome is the sudden attack of, dizziness and unconsciousness caused by heart block., It may be accompanied by convulsions also. In many, patients suffering from heart block, the complete heart, block occurs intermittently. When the block occurs, the, ventricles stop beating immediately. Ectopic pacemaker, (AV node, Purkinje fiber or ventricular muscle) starts, functioning only after 5 to 30 seconds., During this time, the blood circulation is affected, because of lack of ventricular output. Brain cannot, withstand the stoppage of blood supply and oxygen, supply even for 5 seconds. Before the onset of discharge, from ectopic pacemaker, dizziness and fainting occurs., If the discharge of impulses from ectopic pacemaker is, delayed beyond 30 seconds, death occurs., EXTRASYSTOLE, Extrasystole and Compensatory Pause, Extrasystole is the premature contraction of the heart, before its normal contraction. It is caused by an ectopic, focus (discharge of an impulse from any part of the heart, other than the SA node). The ectopic focus produces, an extra beat of the heart that is always followed by, a compensatory pause. Compensatory pause is the, period during which the heart stops in relaxed state., Cause for the compensatory pause, In the cardiac muscle, absolute refractory period, extends throughout contraction period. When the, heart is in extrasystole (because of ectopic focus),, an impulse is discharged from natural pacemaker, SA, node. As this natural impulse reaches the myocardium, during the contraction period of extrasystole, the, myocardium does not give response, because it is, refractory now. For the next beat, the heart has to wait, till the discharge of next natural impulse from SA node., During this time, the heart stops in diastole. It is the, cause for compensatory pause (Chapter 90)., , 1. Atrial Extrasystole, , 2. Nodal Extrasystole, Nodal extrasystole is caused by stimulus arising from, AV node. P wave is merged with QRS complex and all, the chambers of the heart contract together., 3. Ventricular Extrasystole, Ventricular extrasystole is the extrasystole that is, caused by stimulus from ventricular muscle. In this, condition, an extra QRS complex follows the regular T, wave. This QRS complex is prolonged as the impulse is, conducted through ventricular muscle and not through, the conductive system. This QRS complex also has a, high voltage. T wave of this beat is inverted., Conditions when Extrasystole Occurs, Extrasystole is associated with organic diseases of, the heart. Particularly, any ischemic area of ventricular, musculature can produce an ectopic focus., Other conditions which produce extrasystole:, i. Emotions, ii. Severe exhaustion, iii. Excessive ingestion of coffee or alcohol, iv. Excessive smoking, v. Hyperthyroidism, vi. Reflexes elicited from abnormal viscera., PAROXYSMAL TACHYCARDIA, Paroxysmal tachycardia is the sudden attack of, increased heart rate due to ectopic foci arising from, atria, AV node or ventricle. It is also called BouveretHoffmann syndrome., , Increase in heart rate due to ectopic foci arising, from either atria or AV node is called supraventricular
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568 Section 8 t Cardiovascular System, tachycardia (SVT). It differs from ventricular tachycardia,, which does not depend upon atria or AV node. The, attack lasts for a period of few seconds to few hours., It also stops suddenly. After the attack, heart functions, normally. Symptoms include palpitations, chest pain,, rapid breathing and dizziness., Paroxysmal tachycardia is of three types:, 1. Atrial paroxysmal tachycardia, 2. AV nodal paroxysmal tachycardia, 3. Ventricular paroxysmal tachycardia., , 1. Atrial Paroxysmal Tachycardia, Atrial paroxysmal tachycardia is the sudden increase in, heart rate caused by ectopic impulses discharged from, atrial musculature. Heart rate is 150 to 220/minute. P, wave in ECG is inverted, with normal QRST., 2. AV Nodal Paroxysmal Tachycardia –, Bundle of Kent, AV nodal paroxysmal tachycardia is the sudden increase, in heart rate caused by ectopic foci arising from AV node, due to a temporary block in the conductive system. It, also involves circus movement. This type of tachycardia, is very common in some healthy persons who have got, an additional conductive system. This system is formed, by some abnormal junctional tissues constituting a, structure called bundle of Kent. Bundle of Kent connects, the atria and ventricles directly, so the conduction is very, rapid than through the regular conductive system., Circus movement – Re-entry and atrial echo beat, Circus movement is defined as circuitous propagation of, impulses around a structural or functional obstruction,, resulting in re-entry of the impulse and re-excitation, of heart. When there is a sudden and temporary block, in normal conductive system, the impulses from SA, node reach the ventricle through bundle of Kent. By, this time, the blockage in normal conductive system, disappears. Now, the impulse, which passes through, bundle of Kent, after exciting the ventricular muscle,, travels in the opposite direction through the normal, conductive system and finally, it re-enters the AV, node. Re-entered impulse activates the AV node and, depolarizes the atria, resulting in atrial contraction. It is, called atrial echo beat., Re-entered nodal impulse simultaneously spreads, to ventricle through normal conductive system,, completing the circus movement. This circus movement, is repeated producing tachycardia called AV nodal, paroxysmal tachycardia. ECG shows normal QRST, complex. But P wave is mostly absent., , Wolff-Parkinson-White syndrome, Wolff-Parkinson-White syndrome is the condition, characterized by repeated attacks of AV nodal, paroxysmal tachycardia in persons with bundle of Kent., ECG shows short P-R interval with normal QRS complex, and T wave., Lown-Ganong-Levin syndrome, Lown-Ganong-Levin syndrome is another condition, characterized by AV nodal paroxysmal tachycardia., This occurs in persons who have got another type of, abnormal conductive fibers like bundle of Kent. These, fibers also connect atria and distal part of conductive, system directly bypassing the AV node. So the impulse, from SA node reaches ventricle through the abnormal, conductive fibers. After exciting the ventricular muscle,, the impulse travels in opposite direction through normal, conductive system and finally, it re-enters the AV node., The re-entered impulse activates the AV node causing, atrial contraction. ECG shows short P-R interval with, normal QRS complex and T wave., 3. Ventricular Paroxysmal Tachycardia, Ventricular paroxysmal tachycardia is the sudden, increase in heart rate caused by ectopic foci arising, from ventricular musculature. Sometimes, a part of, ventricular muscle, particularly an ischemic area is, excited abnormally, followed by a series of extrasystole., This condition is dangerous as the circus movement, is developed within ventricular muscle. This circus, movement leads to ventricular fibrillation, which is fatal., ATRIAL FLUTTER, Atrial flutter is an arrhythmia characterized by rapid, ineffective atrial contractions, caused by ectopic foci, originating from atrial musculature. It is often associated, with atrial paroxysmal tachycardia. Both the atria beat, rapidly like the wings of a bird, hence the name atrial, flutter., Atrial rate is about 250 to 350/minute. Maximum, number of impulses conducted by AV node is about, 230 to 240 /minute. So, during atrial flutter, the second, degree of heart block occurs. The ratio between atrial, beats and ventricular beats is 2 : 1 or sometimes 3 : 1., Atrial flutter is common in patients suffering from, cardiovascular diseases such as hypertension and, coronary artery disease. Initially, it is marked by, palpitations that are unnoticed. However, prolonged, atrial flutter may lead to atrial fibrillation or heart failure.
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Chapter 96 t Arrhythmia 569, ATRIAL FIBRILLATION, Atrial fibrillation is the type of arrhythmia characterized, by rapid and irregular atrial contractions at the rate, of 300 to 400 beats/minute. It is mostly due to circus, movement of impulses within atrial musculature. P, wave is absent in ECG., Atrial fibrillation is common in old people and, patients with heart diseases. Though it is not lifethreatening, it may cause complications. If it continues, for long time, it may cause blood clot and blockage of, blood flow to vital organs., , iii., iv., v., vi., , Wolff-Parkinson-White syndrome, Lown-Ganong-Levine syndrome, Atrial flutter, Atrial fibrillation., , 3. Ventricular Musculature as Pacemaker, If ventricular muscle becomes the pacemaker, following, arrhythmias are developed:, i. Ventricular extrasystole, ii. Ventricular paroxysmal tachycardia, iii. Ventricular fibrillation., , VENTRICULAR FIBRILLATION, Ventricular fibrillation is the dangerous cardiac arrhythmia, characterized by rapid and irregular twitching of, ventricles. Ventricles beat very rapidly and irregularly, due to the circus movement of impulses within, ventricular muscle. The rate reaches 400 to 500/minute., This is triggered by ventricular extrasystole. This type, of arrhythmia is serious as it leads to death, since the, ventricles cannot pump blood., Ventricular fibrillation is very common during electric, shock and during ischemia of conductive system. It, also occurs in other conditions like coronary occlusion,, chloroform anesthesia, cyclopropane anesthesia,, trauma of heart and disturbances of heart (due to, improper handling) during cardiac surgery., , ABNORMAL PACEMAKER, Abnormal pacemaker is the part of the heart other than, SA node that becomes the pacemaker and discharges, ectopic foci. Various types of arrhythmia develop, when an abnormal pacemaker is activated. These, arrhythmias are already described in this Chapter., Common abnormal pacemakers:, 1. Atrioventricular node, 2. Atrial musculature, 3. Ventricular musculature., , ARTIFICIAL PACEMAKER, Artificial pacemaker is a small electronic device that, is surgically implanted to regulate abnormal heartbeat., It contains a battery powered pulse generator, that, produces electrical impulses capable of stimulating, the heart. This pacemaker is implanted under the skin, over the chest of the patient. Pulses generated by this, device are transmitted to the heart through electrodes., Electrodes connected to the device are inserted and, passed through a vein and positioned in the heart, chambers. The device has a lithium battery that may last, for 10 to 15 years. The outer casing of the pacemaker, is usually made of titanium, which is rarely rejected by, body’s immune system., Pulse generator of the pacemaker has multiple, functions. It is programmed to cope up with the needs of, the individual patient., , CURRENT OF INJURY, , When AV node becomes the pacemaker, the following, arrhythmias occur:, i. AV nodal rhythm, ii. AV nodal extrasystole, iii. AV nodal paroxysmal tachycardia., , Current of injury means flow of current from an injured, region of heart to the unaffected part. When ischemia, occurs in any part of the ventricular musculature due, to coronary occlusion, that part of ventricle becomes, depolarized either partially or completely and the, repolarization does not occur. It causes flow of current, from affected (depolarized) part to unaffected part of the, ventricular muscle., Current of injury in myocardial infarction affects the, ECG pattern and cardiac vector. In ECG, the J point, and ST segments are displaced (Chapter 94). Deviation, of cardiac axis is also common during the current of, injury., , 2. Atrial Musculature as Pacemaker, , Cardiac Axis, , Following arrhythmias occur if atrial musculature, becomes the pacemaker:, i. Atrial extrasystole, ii. Atrial paroxysmal tachycardia, , In the infarction of anterior wall of the ventricle, the, cardiac axis (vector) is deviated to right up to +150° due, to current of injury and in the posterior wall infarction,, there is left axis deviation up to –95°., , 1. AV Node as Pacemaker
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Effect of Changes in, Electrolyte Concentration, on Heart, , Chapter, , 97, , INTRODUCTION, EFFECT OF CHANGES IN SODIUM ION CONCENTRATION, EFFECT OF CHANGES IN POTASSIUM ION CONCENTRATION, , , , EFFECT OF HYPERKALEMIA, EFFECT OF HYPOKALEMIA, , EFFECT OF CHANGES IN CALCIUM ION CONCENTRATION, , , , EFFECT OF HYPERCALCEMIA, EFFECT OF HYPOCALCEMIA, , EXPERIMENTAL EVIDENCES, , INTRODUCTION, , EFFECT OF HYPERKALEMIA, , Distribution of electrolytes in extracellular fluid and, intracellular fluid is responsible for the electrical activity, of the tissues including myocardium. Thus, any change, in the concentration of any electrolyte will definitely alter, the electrical activity of cardiac muscle., , Hyperkalemia decreases:, 1. Resting membrane potential, leading to hyperpolarization, 2. Excitability of the muscle., Effects of hyperkalemia on the excitability of cardiac, muscle, depend upon the severity of hyperkalemia., , EFFECT OF CHANGES IN, SODIUM ION CONCENTRATION, Normal sodium ion concentration in blood is 135 to 145, mEq/L. Change in concentration of sodium ion does not, alter the electrical activity of heart severely. Only the low, level of sodium ion in body fluids reduces the electrical, activity of cardiac muscle and electrocardiogram (ECG), shows low-voltage waves., Changes in the concentration of potassium and, calcium ions have significant effects on heart., , EFFECT OF CHANGES IN, POTASSIUM ION CONCENTRATION, Normal potassium ion concentration in blood is about, 3.5 to 5 mEq/L. Changes in ECG appear when the, potassium level increases to 6 mEq/L (hyperkalemia) or, when it decreases to 2 mEq/L (hypokalemia)., , Changes in ECG When Potassium Level, Increases to 6 or 7 mEq/L, T wave is tall and tented. P-R interval and QRS complex, are normal., Changes in ECG When Potassium Level, Increases to 8 mEq/L, P-R interval and the duration of QRS complex are, prolonged because, hyperkalemia decreases the rate, of conduction. P wave may be small., Changes in ECG When Potassium Level, Increases beyond 9 mEq/L, Severe hyperkalemia makes the atrial muscle, unexcitable. So, P wave is absent in ECG. QRS complex, merges with T wave. This condition is fatal because, it
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Chapter 97 t Effect of Changes in Electrolyte Concentration on Heart 571, leads to ventricular fibrillation or stoppage of heart in, diastole, due to the lack of excitability., , the heart muscle. In clinical conditions, the effect of, hypercalcemia is very rare., , EFFECT OF HYPOKALEMIA, , Changes in ECG, , Hypokalemia decreases the sensitivity of heart muscle., Changes in ECG When Potassium Level, Falls to 2 mEq/L, 1. S-T segment is depressed, 2. T wave is small, flat or inverted, 3. U wave appears. Sometimes, the U wave merges, with T wave. Because of this, the Q-T interval is, mistaken for being prolonged., Changes in ECG When Potassium Level Falls, below 2 mEq/L, 1. Depression of S-T segment below the isoelectric, baseline, 2. Inversion of T wave, 3. Appearance of prominent U wave, 4. Prolongation of P-R interval., , EFFECT OF CHANGES IN, CALCIUM ION CONCENTRATION, Normal concentration of calcium ion in blood is 9 to 11, mg/dL (4.5 to 5.5 mEq/L). Mostly, hypocalcemia affects, the heart, rather than hypercalcemia., EFFECT OF HYPERCALCEMIA, Hypercalcemia is the elevation in blood calcium, level. It increases the excitability and contractility of, , 1. Shortening of duration of S-T segment, 2. Shortening of QT interval, 3. Appearance of U wave., Calcium Rigor, Stoppage of the heart in systole, due to hypercalcemia, is called the calcium rigor. It can be demonstrated in, experimental animals by infusing large quantity of, calcium. Calcium rigor is a reversible phenomenon and, the heart starts functioning normally, when the calcium, ions are washed., EFFECT OF HYPOCALCEMIA, Hypocalcemia is the reduction in blood calcium level. It, reduces the excitability of the cardiac muscle., Changes in ECG, 1. Prolongation of S-T segment, 2. Prolongation of Q-T interval, 3. Appearance of a prominent U wave., , EXPERIMENTAL EVIDENCES, Effects of ions on heart are demonstrated experimentally by perfusion of heart from animals such as frog, and rabbit.
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Chapter, , Cardiac Output, , 98, , INTRODUCTION, DEFINITIONS AND NORMAL VALUES, , , , , STROKE VOLUME, MINUTE VOLUME, CARDIAC INDEX, , EJECTION FRACTION, CARDIAC RESERVE, VARIATIONS IN CARDIAC OUTPUT, , , , PHYSIOLOGICAL VARIATIONS, PATHOLOGICAL VARIATIONS, , DISTRIBUTION OF CARDIAC OUTPUT, FACTORS MAINTAINING CARDIAC OUTPUT, , , , , , VENOUS RETURN, FORCE OF CONTRACTION, HEART RATE, PERIPHERAL RESISTANCE, , MEASUREMENT OF CARDIAC OUTPUT, , , , DIRECT METHODS, INDIRECT METHODS, , CARDIAC CATHETERIZATION, , , , , , DEFINITION, CONDITIONS WHEN CARDIAC CATHETERIZATION IS PERFORMED, PROCEDURE, USES OF CARDIAC CATHETERIZATION, , INTRODUCTION, Cardiac output is the amount of blood pumped from, each ventricle. Usually, it refers to left ventricular output, through aorta. Cardiac output is the most important, factor in cardiovascular system, because rate of blood, flow through different parts of the body depends upon, cardiac output., , DEFINITIONS AND NORMAL VALUES, Usually, cardiac output is expressed in three ways:, , 1. Stroke volume, 2. Minute volume, 3. Cardiac index., However, in routine clinical practice, cardiac output, refers to minute volume., STROKE VOLUME, Stroke volume is the amount of blood pumped out by, each ventricle during each beat., Normal value: 70 mL (60 to 80 mL) when the heart rate, is normal (72/minute).
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Chapter 98 t Cardiac Output 573, MINUTE VOLUME, Minute volume is the amount of blood pumped out by, each ventricle in one minute. It is the product of stroke, volume and heart rate:, Minute volume = Stroke volume × Heart rate, Normal value: 5 L/ventricle/minute., CARDIAC INDEX, Cardiac index is the minute volume expressed in relation, to square meter of body surface area. It is defined as, the amount of blood pumped out per ventricle/minute/, square meter of the body surface area., Normal value: 2.8 ± 0.3 L/square meter of body surface, area/minute (in an adult with average body surface area, of 1.734 square meter and normal minute volume of, 5 L/minute)., , EJECTION FRACTION, Ejection fraction is the fraction of end diastolic volume, that is ejected out by each ventricle. Normal ejection, fraction is 60% to 65%. Refer Chapter 91 for details., , CARDIAC RESERVE, Cardiac reserve is the maximum amount of blood that, can be pumped out by heart above the normal value., Cardiac reserve plays an important role in increasing, the cardiac output during the conditions like exercise., It is essential to withstand the stress of exercise., Cardiac reserve is usually expressed in percentage., In a normal young healthy adult, the cardiac reserve is, 300% to 400%. In old age, it is about 200% to 250%., It increases to 500% to 600% in athletes. In cardiac, diseases, the cardiac reserve is minimum or nil., , VARIATIONS IN CARDIAC OUTPUT, PHYSIOLOGICAL VARIATIONS, 1. Age: In children, cardiac output is less because of, less blood volume. Cardiac index is more than that, in adults because of less body surface area., 2. Sex: In females, cardiac output is less than in males, because of less blood volume. Cardiac index is, more than in males, because of less body surface, area., 3. Body build: Greater the body build, more is the, cardiac output., 4. Diurnal variation: Cardiac output is low in early, morning and increases in day time. It depends, upon the basal conditions of the individuals., , 5. Environmental temperature: Moderate change in, temperature does not affect cardiac output. Increase, in temperature above 30°C raises cardiac output., 6. Emotional conditions: Anxiety, apprehension and, excitement increases cardiac output about 50% to, 100% through the release of catecholamines, which, increase the heart rate and force of contraction., 7. After meals: During the first one hour after taking, meals, cardiac output increases., 8. Exercise: Cardiac output increases during exercise, because of increase in heart rate and force of, contraction., 9. High altitude: In high altitude, the cardiac output, increases because of increase in secretion of, adrenaline. Adrenaline secretion is stimulated by, hypoxia (lack of oxygen)., 10. Posture: While changing from recumbent to upright, position, the cardiac output decreases., 11. Pregnancy: During the later months of pregnancy,, cardiac output increases by 40%., 12. Sleep: Cardiac output is slightly decreased or it is, unaltered during sleep., PATHOLOGICAL VARIATIONS, Increase in Cardiac Output, Cardiac output increases in the following conditions:, 1. Fever: Due to increased oxidative processes, 2. Anemia: Due to hypoxia, 3. Hyperthyroidism: Due to increased basal metabolic, rate., Decrease in Cardiac Output, Cardiac output decreases in the following conditions:, 1. Hypothyroidism: Due to decreased basal metabolic, rate, 2. Atrial fibrillation: Because of incomplete filling of, ventricles, 3. Incomplete heart block with coronary sclerosis or, myocardial degeneration: Due to defective pumping, action of the heart, 4. Congestive cardiac failure: Because of weak, contractions of heart, 5. Shock: Due to poor pumping and circulation, 6. Hemorrhage: Because of decreased blood volume., , DISTRIBUTION OF CARDIAC OUTPUT, The whole amount of blood pumped out by the right, ventricle goes to lungs. But, the blood pumped by the, left ventricle is distributed to different parts of the body.
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574 Section 8 t Cardiovascular System, Fraction of cardiac output distributed to a particular, region or organ depends upon the metabolic activities, of that region or organ., Distribution of Blood Pumped out of Left Ventricle, Distribution of blood pumped out of left ventricle to, different organs and the percentage of cardiac output, are given in Table. 98.1. Heart, which pumps the blood, to all other organs, receives the least amount of blood., Liver receives maximum amount of blood., , FACTORS MAINTAINING CARDIAC OUTPUT, Cardiac output is maintained (determined) by four, factors:, 1. Venous return, 2. Force of contraction, 3. Heart rate, 4. Peripheral resistance., 1. VENOUS RETURN, , thoracic cavity expands and makes the intrathoracic, pressure more negative. It increases the diameter of, inferior vena cava, resulting in increased venous return., At the same time, descent of diaphragm increases the, intra-abdominal pressure, which compresses abdominal, veins and pushes the blood upward towards the heart, and thereby the venous return is increased (Fig. 98.1)., Respiratory pump is much stronger in forced, respiration and in severe muscular exercise., ii. Muscle Pump, Muscle pump is the muscular activity that helps in, return of the blood to heart. During muscular activities,, the veins are compressed or squeezed. Due to the, presence of valves in veins, during compression the, blood is moved towards the heart (Fig. 98.2). When, muscular activity increases, the venous return is more., When the skeletal muscles contract, the vein located, in between the muscles is compressed. Valve of the vein, , Venous return is the amount of blood which is returned to, heart from different parts of the body. When it increases,, the ventricular filling and cardiac output are increased., Thus, cardiac output is directly proportional to venous, return, provided the other factors (force of contraction,, heart rate and peripheral resistance) remain constant., Venous return in turn, depends upon five factors:, i. Respiratory pump, ii. Muscle pump, iii. Gravity, iv. Venous pressure, v. Sympathetic tone., i. Respiratory Pump, Respiratory pump is the respiratory activity that helps, the return of blood, to heart during inspiration. It is also, called abdominothoracic pump. During inspiration,, TABLE 98.1: Distribution of blood pumped, out of left ventricle, Organ, , Amount of blood, (mL/ minute), , Percentage, , Liver, , 1,500, , 30, , Kidney, , 1,300, , 26, , Skeletal muscles, , 900, , 18, , Brain, , 800, , 16, , Skin, bone and GI, tract, , 300, , 6, , Heart, , 200, , 4, , 5,000, , 100, , Total, , FIGURE 98.1: Effect of respiratory pump on venous return
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Chapter 98 t Cardiac Output 575, proximal to the contracting muscles (Fig. 98.2 A) is, opened and the blood is propelled towards the heart., Valve of the vein distal to the muscles is closed by the, back flow of blood., During relaxation of the muscles (Fig. 98.2 B), the, valve proximal to muscles closes and prevents the back, flow of blood. The valve distal to the muscles opens, and allows the blood to flow upwards., iii. Gravity, Gravitational force reduces the venous return. When a, person stands for a long period, gravity causes pooling, of blood in the legs, which is called venous pooling., Because of venous pooling, the amount of blood, returning to heart decreases., , iv. Venous Pressure, Venous pressure also affects the venous return. Pressure, in the venules is 12 to 18 mm Hg. In the smaller and, larger veins, the pressure gradually decreases. In the, great veins, i.e. inferior vena cava and superior vena, cava, the pressure falls to about 5.5 mm Hg. At the, junction of venae cavae and right atrium, it is about 4.6, mm Hg. Pressure in the right atrium is still low and it, alters during cardiac action. It falls to zero during atrial, diastole. This pressure gradient at every part of venous, tree helps as a driving force for venous return., v. Sympathetic Tone, Venous return is aided by sympathetic or vasomotor tone, (Chapter 103), which causes constriction of venules., Venoconstriction pushes the blood towards heart., , FIGURE 98.2: Mechanism of muscle pump. A. During, contraction of the muscle; B. During relaxation of the muscle., , Thus, force of contraction of heart and cardiac, output are directly proportional to preload., Afterload, Afterload is the force against which ventricles must, contract and eject the blood. Force is determined by, the arterial pressure. At the end of isometric contraction, period, semilunar valves are opened and blood is ejected, into the aorta and pulmonary artery. So, the pressure, increases in these two vessels. Now, the ventricles have, to work against this pressure for further ejection. Thus,, the afterload for left ventricle is determined by aortic, pressure and afterload for right ventricular pressure is, determined by pressure in pulmonary artery., Force of contraction of heart and cardiac output are, inversely proportional to afterload., , 2. FORCE OF CONTRACTION, Cardiac output is directly proportional to the force of, contraction, provided the other three factors remain, constant. According to Frank-Starling law, force of, contraction of heart is directly proportional to the initial, length of muscle fibers, before the onset of contraction., Force of contraction depends upon preload and, afterload., , 3. HEART RATE, Cardiac output is directly proportional to heart rate, provided, the other three factors remain constant., Moderate change in heart rate does not alter the, cardiac output. If there is a marked increase in heart, rate, cardiac output is increased., If there is marked decrease in heart rate, cardiac, output is decreased., , Preload, Preload is the stretching of the cardiac muscle fibers, at the end of diastole, just before contraction. It is due, to increase in ventricular pressure caused by filling, of blood during diastole. Stretching of muscle fibers, increases their length, which increases the force of, contraction and cardiac output., , 4. PERIPHERAL RESISTANCE, Peripheral resistance is the resistance offered to, blood flow at the peripheral blood vessels. Peripheral, resistance is the resistance or load against which the, heart has to pump the blood. So, the cardiac output is, inversely proportional to peripheral resistance.
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576 Section 8 t Cardiovascular System, Resistance is offered at arterioles so, the arterioles, are called resistant vessels. In the body, maximum, peripheral resistance is offered at the splanchnic, region. Other details of peripheral resistance are given, in Chapter 102., , blood vessel passes through the cleft. The probe almost, encircles the blood vessel. The probe is connected to, the electronic device to measure the volume of blood, flow., Advantage of this flowmeter is that the blood vessel, need not be cut open., , MEASUREMENT OF CARDIAC OUTPUT, , Ultrasonic Doppler flowmeter, , Cardiac output is measured by direct methods and, indirect methods. Direct methods are used only in, animals. Indirect methods are used both in animals and, human beings., , Principle: Ultrasound is the sound with very high, frequency. It is very much beyond the audible range, of human ears. The waves of the ultrasound are, transmitted through a blood vessel. These sound, waves are called transmitted waves. While passing, through the blood vessels, the sound waves hit against, the blood cells, particularly the red blood cells and are, reflected back. Frequency of the reflected waves is, different from that of the transmitted waves. This effect, is called the Doppler effect (named after the discoverer, Johann Christian Doppler). Alteration in the frequency, of reflected waves depends upon the velocity of blood, flowing through the blood vessel. By detecting the, differences between frequencies of transmitted and, reflected sound waves, the velocity of blood flow and, then the volume of blood flow are determined., Instrument: Ultrasonic device has piezoelectric crystals,, which produce the ultrasonic waves and act as sensors, to receive the reflected waves. This device is connected, to an electronic equipment, which detects the difference, between the frequencies of transmitted and reflected, waves and thereby, determines the velocity of blood, flow and the volume of blood flow., , MEASUREMENT OF CARDIAC OUTPUT, BY DIRECT METHODS, Direct methods used to measure cardiac output in, animals:, 1. By using cardiometer, 2. By using flowmeter., 1. By Using Cardiometer, This is described in Chapter 91., 2. By Using Flowmeter, Mechanical flowmeter, Mechanical flowmeter is used to measure cardiac, output or the amount of blood flow to any organ. It is, used only in animals. It has an inlet, a measuring device, in the middle and an outlet. Aorta or the artery entering, any organ is cut. Inlet and outlet of the flowmeter are, inserted into cut ends of the blood vessel. When the, blood passes through the flowmeter, the measuring, device determines the amount of blood flow (Fig. 99.1)., Electromagnetic flowmeter, Principle: Principle of this flowmeter is to develop an, electromagnetic field by means of two coils of wire. If, the coils are placed on either side of a blood vessel,, the electromagnetic field is produced around the, vessel. When blood flows through the vessel, there, is an alteration in the electromagnetic field. By using, appropriate electrodes, the changes in the magnetic, field can be detected. By connecting electrodes to an, electronic device, velocity of blood flow is determined, on the basis of changes in the magnetic field. From, the velocity of blood flow, the volume of blood flow is, calculated., Instrument: An electromagnetic probe is devised with, the electromagnetic coils and the electrodes. The probe, has a cleft and it is fixed in such a way that the intact, , Disadvantages of Direct Methods, i. Direct methods to measure cardiac output can, be used only in animals, ii. Blood vessel has to be cut open at the risk of, animal’s life, iii. While using cardiometer, the size of the, cardiometer must be suitable for the size of the, heart, iv. While using mechanical flowmeter, diameter, of inlet and the outlet of the flowmeter must be, equivalent to the diameter of the blood vessel., MEASUREMENT OF CARDIAC OUTPUT, BY INDIRECT METHODS, Several methods are available to measure cardiac, output. Each method has got its own advantages, and disadvantages. Generally, the safe and accurate, method is preferred. In view of safety, always noninvasive methods are preferred. The invasive method
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Chapter 98 t Cardiac Output 577, is also accepted provided, it gives accurate results. In, addition to providing measurement of cardiac output,, nowadays the methods are expected to provide other, hemodynamic data and some useful information about, the structure and movements of valves and chambers, of the heart., Invasive and Non-invasive Methods, Invasive method refers to a procedure which involves, invasion or penetration of healthy tissues, organs or, parts of the body, by means of perforation, puncture,, incision, injection or catheterization. Non-invasive, method means the procedure that does not involve, invasion or penetration of tissues, organs or parts of the, body., Different Indirect Methods, Indirect methods used to measure cardiac output:, 1. By using Fick principle, 2. Indicator (dye) dilution technique, 3. Thermodilution technique, 4. Ultrasonic Doppler transducer technique, 5. Doppler echocardiography, 6. Ballistocardiography., , Modification of Fick principle to, measure cardiac output, Fick principle is modified to measure the cardiac output, or a part of cardiac output (amount of blood to an organ)., Thus, cardiac output or the amount of blood flowing, through an organ in a given unit of time is determined, by the formula:, , Cardiac output =, , Arteriovenous difference of the, substance across the organ, By modifying Fick principle, cardiac output is, measured in two ways:, i. By using oxygen consumption, ii. By using carbon dioxide given out., Measurement of Cardiac Output by, Using Oxygen Consumption, Fick principle is used to measure the cardiac output, by determining the amount of oxygen consumed in the, body in a given period of time and dividing this value by, the arteriovenous difference across the lungs., , 1. By Using Fick Principle, Adolph Fick described Fick principle in 1870. According, , to this principle, the amount of a substance taken up, by an organ (or by the whole body) or given out in a, unit of time is the product of amount of blood flowing, through the organ and the arteriovenous difference of, the substance across the organ., Amount of, Amount of, Arteriovenous, substance, = blood, ×, difference, taken or given, flow/minute, For example,, Amount of blood flowing through lungs is 5,000 mL/, minute, O2 content in arterial blood = 20 mL/100 mL of blood, O2 content in venous blood = 15 mL/100 mL of blood, Amount of, Amount of, Arteriovenous, oxygen, = blood, × difference of O2, moved from, flow/minute, lungs to blood, = 5,000 x, , = 5,000 x, , 20 – 15, 100, 5, , = 250, 100, Amount of oxygen moved from lungs to blood, = 250 mL/minute, , Amount of substance taken or, given by the organ/minute, , Cardiac output =, , O2 consumed (in mL/minute), Arteriovenous O2 difference, , Oxygen consumption: Amount of oxygen consumed is, measured by using a respirometer or BMR apparatus, (Benedict Roth apparatus)., , Oxygen content in arterial blood: Blood is collected from, any artery to determine the oxygen content in arterial, blood. Oxygen content is determined by blood gas, analysis., Oxygen content in venous blood: Only mixed venous, blood is used to determine the oxygen content of venous, blood, since oxygen content is different in different, veins. Mixed venous blood is collected from right atrium, or pulmonary artery. It is done by introducing a catheter, through basilar vein of forearm. Oxygen is determined, from this blood by blood gas analysis (Fig. 98.3)., Calculation, For example, in a subject, the following data are, obtained:, O2 consumed (by lungs), = 250 mL/minute, O2 content in arterial blood = 20 mL/100 mL of blood, O2 content in venous blood = 15 mL/100 mL of blood, Cardiac output =, , O2 consumed (in mL/minute), Arteriovenous O2 difference
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578 Section 8 t Cardiovascular System, , =, , 250, , =, , 250 × 100, , 5/100, , 5, , = 5,000 mL/minute, 5 mL of oxygen is taken by 100 mL of blood while, passing through the lungs. Thus, 250 mL of oxygen, is taken by 5,000 mL of blood. Since cardiac output, is equivalent to the amount of blood passing through, pulmonary circulation, the cardiac output = 5 L/minute., , Since cardiac output is equal to the amount of blood, passing through lungs (pulmonary circulation), the, cardiac output = 5 L/minute, Nitrous oxide is also used to measure cardiac output, by applying Fick principle., Advantage of measurement of cardiac, output by Fick principle, The results are accurate., Disadvantage, , Measurement of Cardiac Output by, Using Carbon Dioxide, Cardiac output is also measured by knowing the, arteriovenous difference of carbon dioxide and amount, of carbon dioxide given out (removed) by lungs (Fig., 98.4). Thus:, Cardiac output =, , CO2 evolved (in mL/minute), Arteriovenous CO2 difference, , Fick principle is an invasive method and involves the, insertion of catheter through subject vein., 2. Indicator (Dye) Dilution Method, Indicator dilution technique is described in detail in, Chapter 6. Marker substance used to measure cardiac, output is lithium chloride., Advantage, The results are accurate., , Calculation, For example, in a subject, CO2 removed by lungs, = 200 mL/minute, CO2 content in arterial blood = 56 mL/100 mL of blood, CO2 content in venous blood = 60 mL/100 mL of blood, 200, , Cardiac output =, , 60 – 56 mL/100 mL, 200 ×100, =, 4, = 5,000 mL = 5 L/minute, , FIGURE 98.3: Oxygen consumption, , Disadvantage, Indicator dilution method is an invasive method and, involves injection of marker substance., 3. Thermodilution Technique, Cardiac output can also be measured by thermodilution, technique or thermal indicator method. This method is, the modified indicator dilution method. It is the popular, method to measure cardiac output., In this method, a known volume of cold sterile, solution is injected into the right atrium via inferior vena, , FIGURE 98.4: Carbon dioxide given out
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Chapter 98 t Cardiac Output 579, cava by using a catheter. Cardiac output is measured by, determining the resultant change in the blood temperature, in pulmonary artery. For this purpose, two thermistors, (temperature transducers) are used. One of them is, placed in the inferior vena cava and the second one is, placed in pulmonary artery. A pulmonary artery catheter, is used to place the thermistors in their positions., A known quantity of cold saline or cold dextrose, solution is injected into inferior vena cava. Thermistors, determine the temperature of blood entering the heart, via inferior vena cava and temperature of blood leaving, the heart via pulmonary artery. From the values of, temperature, cardiac output is measured by applying, indicator dilution technique., Advantages, Results are accurate in this method. Even low cardiac, output can be measured. Saline is also harmless., Catheter is also used to determine hemodynamic, pressures and to collect mixed venous blood., Disadvantage, Thermodilution technique is an invasive method and it, requires catheterization., Continuous cardiac output measurement catheter, Cardiac output can be measured continuously by using, a modified pulmonary artery catheter called continuous, cardiac output measurement catheter (CCO catheter)., CCO catheter works on thermodilution principle. Instead, of injecting cold saline, a heating filament which delivers, heat directly to blood is used. The heating filament is fitted, to the ventricular portion of the catheter. Cardiac output, is measured as done in thermodilution technique. This, method is commonly used in intensive care unit (ICU)., 4. Esophageal Ultrasonic Doppler, Transducer Technique, Esophageal ultrasonic doppler transducer technique, involves insertion of a flexible probe into midthoracic, part of esophagus. A pulse wave ultrasonic Doppler, transducer is fixed at the tip of the probe. This transducer, calculates the velocity of blood flow in descending aorta, (refer ultrasonic Doppler flow meter for details). The, diameter of aorta is determined by echocardiography, (see below). Cardiac output is calculated by using the, values of velocity of blood flow and diameter of aorta., , Disadvantages, Esophageal ultrasonic doppler transducer is an invasive, method and results are less accurate., 5. Doppler Echocardiography, Doppler echocardiography is a method for detecting, the direction and velocity of moving blood within the, heart. This is also a popular method to measure cardiac, output., Echocardiography is a diagnostic procedure, which, uses the ultrasound waves (more than 20,000 Hz) to, produce the image of the heart muscle. Ultrasound, waves which reflect or echo off the heart can determine, the size, shape, movement of the valves and chambers, and the flow of blood through the heart., During echocardiographic examination, the patient, lies bare-chested on the examination table. A special, gel is spread over the chest to help the transducer, make good contact and slide smoothly over the skin., The transducer is a small hand operated device,, which is attached to machine by a flexible cable. The, transducer is placed against the chest. The transducer, produces and directs ultrasound waves into the chest., Some of the waves get reflected (or echoed) back to, the transducer. The reflection of sound waves depends, upon the type of tissues and blood. The reflected sound, waves are received by the transducer and translated, into an image of the heart and displayed on a monitor, or recorded on paper or tape., Echocardiography may also show the abnormalities, in functioning of heart valves or damage to the, myocardium from an earlier heart attack., When Doppler principle is applied in echocardiography, it enables the determination of direction,, rate and other characteristics of blood flow. Doppler, echocardiography is based upon the changes in, frequency of the reflected sound waves from red blood, cells (refer ultrasonic Doppler flow meter for details)., By Doppler echocardiography, the velocity of blood, flow through aortic valve is determined. The diameter, of the aorta is determined by simple echocardiography., From these values, cardiac output is calculated., Advantage, Doppler echocardiography is a non-invasive technique. It, also provides other useful information about the structures, and movements of valves and chambers of heart., , Advantages, , Disadvantage, , The cardiac output can be measured continuously. This, can be used during cardiac surgery., , Doppler echocardiography method provides, accurate results. It requires well trained operator., , less
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580 Section 8 t Cardiovascular System, 6. Ballistocardiographic Method, , PROCEDURE, , Ballistocardiography is the technique to record the, movements of the body caused by ballistic recoil,, associated with contraction of heart and ejection of, blood. It is based on Newton’s third law of motion (for, every action there is an equal and opposite reaction)., When heart pumps blood into aorta and pulmonary, artery, a recoiling force is exerted against heart and the, body. It is similar to that of ballistic recoil when a bullet, is fired from a riffle., Pulsations due to this ballistic recoil can be recorded, graphically by making the subject to lie on a suspended, bed, movable in the long axis of the body. The cardiac, output is determined by analyzing the graph obtained., , Cardiac catheterization is performed by insertion, of catheter into the peripheral blood vessel through, skin, by needle puncture. This procedure is called, percutaneous insertion of catheter., , Advantage, The only advantage of ballistocardiography is that it is a, non-invasive method., Disadvantage, Ballistocardiography is not a commonly used technique, because it involves cumbersome procedures for, calibrating the equipment and analyzing the graph. It, also does not provide accurate results., , CARDIAC CATHETERIZATION, DEFINITION, Catheter is a thin radiopaque tube, made up of, elastic web, rubber, plastic, glass or metal. Cardiac, catheterization is an invasive procedure in which a, catheter is inserted intravascularly into any chamber of, the heart or a blood vessel., Cardiac catheterization is helpful to study the, different variables of hemodynamics, both in normal and, diseased states. Cardiac catheterization was discovered, by a German medical student Werner Forsmann, who, practiced this technique first on himself., CONDITIONS WHEN CARDIAC, CATHETERIZATION IS PERFORMED, Cardiac catheterization is generally performed:, 1. When clinical assessments indicate rapid deterioration of patient’s health and immediate treatment., This is the most common condition when cardiac, catheterization is needed., 2. Whenever there is a need to confirm the suspected, cardiac disease of a patient, 3. Whenever there is need to determine anatomical and, physiological status of heart and blood vessels., , Left Heart Catheterization, Left heart catheterization is done by passing a catheter, through femoral artery, brachial artery or axillary artery., Catheter is guided into left ventricle under fluoroscopic, observation via aorta. From left ventricle, the catheter is, advanced into left atrium., In patients with aortic stenosis or prosthetic (artificial), valve, the direct left ventricular puncture is performed., Under local anesthesia, a needle with a catheter is, inserted through the thoracic wall at the level of apex, beat. When the needle enters left ventricle, the catheter, is advanced through the needle into left ventricle and, later the needle is removed., Latest technology includes catheterization through, radial artery, which is called transradial catheterization., Right Heart Catheterization, Right heart catheterization is usually performed by, venous puncture via femoral vein. Catheter can also, be introduced via internal jugular vein, subclavian, vein or medial vein. Under fluoroscopic observation,, the catheter is advanced into right atrium. From right, atrium, it can be guided into right ventricle and also into, pulmonary artery., USES OF CARDIAC CATHETERIZATION, Cardiac catheterization is useful for both diagnostic and, therapeutic purposes. It gives crucial information about, the need for cardiac surgery, coronary angioplasty and, other therapeutic procedures. It also gives information, about anticipated risks and reversibility in the patient’s, condition during cardiac surgery or other therapeutic, interventions., , Diagnostic Uses of Cardiac Catheterization, 1. Blood samples are collected during cardiac, catheterization to measure oxygen saturation and, the concentration of ischemic metabolites like, lactate, 2. Cardiac output is measured by using Fick principle,, indicator dilution technique or thermodilution, technique during cardiac catheterization
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Chapter 98 t Cardiac Output 581, 3. Angiography is done with the help of catheterization., Angiography or arteriography is the diagnostic or, therapeutic radiography (imaging technique), in, which the fluoroscopic picture is used to visualize, the blood filled structures like cardiac chambers,, arteries and veins of heart and other blood vessels,, by using a radiopaque contrast medium. It is, used to determine the obstruction or occlusion of, coronary blood vessels or other blood vessels. It is, also used to determine the anomalies of coronary, blood vessels., 4. Various pressures are determined by attaching a, pressure transducer to the cardiac catheter., Right heart catheterization is used to measure:, i. Right atrial pressure, ii. Right ventricular pressure, iii. Pulmonary arterial pressure, iv. Pulmonary capillary wedge pressure., Left heart catheterization is used to measure:, i. Aortic pressure, ii. Left ventricular pressure, iii. Left atrial pressure., Therapeutic Uses of Cardiac Catheterization –, Interventional Cardiology, Cardiac catheterization is performed for various, therapeutic procedures. Interventional cardiology is, a branch of cardiology that deals with performance, of traditional surgical procedures by cardiac, catheterization. It helps in:, 1. Thrombolysis, 2. Percutaneous transluminal coronary angioplasty, 3. Laser coronary angioplasty, 4. Catheter ablation., 1. Thrombolysis, Thrombolysis (reperfusion therapy) is the procedure, used to break up and dissolve a thrombus (clot), in the coronary artery of patient affected by acute, myocardial infarction due to coronary thrombus. Cardiac, catheterization is used for intracoronary administration, of thrombolytic agents which cause thrombolysis., , Thrombolytic agents:, i. Tissue plasminogen activator, ii. Streptokinase, iii. Urokinase., All these thrombolytic agents convert plaminogen, into plasmin, which degrades fibrin in clot and restore, normal blood flow., 2. Percutaneous transluminal coronary angioplasty, Coronary angioplasty means the correction of, narrowed or totally obstructed lumen of blood vessels, by mechanical methods. In percutaneous transluminal, coronary angioplasty (PTCA), a narrowed coronary, artery is dilated by inflating a balloon attached to, the tip of catheter that is introduced into the blood, vessel. Sometimes, a stent (expandable wire mesh), is introduced into the corrected blood vessel by the, catheter to keep the vessel in dilated state., 3. Laser coronary angioplasty, Catheter is also used to emit laser (Light amplification, by stimulated emission of radiation) energy. Laser, energy which is emitted into the occluded coronary, artery vaporizes the atherosclerotic plaque in the, diseased vessel. This technique is called laser coronary, angioplasty., 4. Catheter ablation, Catheter ablation is the procedure to destroy (ablate) an, area of cardiac tissue that blocks the electrical pathway, or produces abnormal electrical impulses, resulting in, cardiac arrhythmia such as supraventricular tachycardia, (SVT) or Wolff-Parkinson-White syndrome (Chapter 96)., It involves advancing a catheter (with electrodes, attached to its tip) towards the heart via either femoral, vein or subclavian vein. When the catheter enters right, atrium, arrhythmia is induced. Then the electrodes at, the tip of catheter record the electrical potentials. By, using these recordings, the area of faulty electrical, site is pinpointed. This procedure is called electrical, mapping., , Once the damaged site is confirmed, radiofrequency, energy is used to destroy the small amount of tissue, , that disturbs the electrical flow through the heart. Thus,, the healthy heart rhythm is restored. Tissue is also, destroyed by freezing with intense cold (cryoablation).
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Heart-lung Preparation, , Chapter, , 99, , INTRODUCTION, PROCEDURE, USES OF HEART-LUNG PREPARATION, , INTRODUCTION, Heart-lung preparation is an experimental set up,, devised by Starling. It is used to demonstrate the effects, of various factors on the activities of heart, particularly, heart rate and cardiac output. This preparation is also, used to record the cardiac function curves., , PROCEDURE, Heart-lung preparation is usually done in dogs. After, giving anesthesia, neck of the dog is opened and a, tracheal cannula is inserted into the trachea. Tracheal, cannula is connected to a respiratory pump, so that, respiration in the animal is controlled artificially, to avoid, any disturbance during the experimental procedure, (Fig. 99.1)., Then, chest is opened and an arterial cannula, is inserted into one of the branches of aorta. All the, other branches from arch of aorta and descending, aorta are ligated. Arterial cannula is connected to two, instruments:, 1. Mercury manometer to measure the arterial blood, pressure, 2. Air bottle, which provides elasticity artificially (as in, the case of arterial wall)., Thus, the blood ejected from left ventricle passes, into air bottle through the arterial cannula and rubber, tubes. From the air bottle, the blood is diverted through, a tube which provides artificial resistance. Air bottle is, also connected to a pressure bottle. Pressure bottle, is attached to a pressure pump. This pump is used to, maintain the pressure within the set up., , Artificial resistance is offered by applying pressure, surrounding the resistance tube. Resistance tube is, also connected to a manometer., After passing through the resistance tube, blood, is allowed to flow through a warming glass coil, which, is kept inside a water bath with a heater. Temperature, of water bath is controlled, so that the temperature of, blood could be maintained., Warming coil is connected to a venous reservoir, through a flowmeter, which determines the amount, of blood flow (cardiac output). Venous reservoir is, connected to superior vena cava by a rubber tube. A, screw type clamp is fitted to the rubber tube. This clamp, is used to adjust the amount of blood returning to heart, (venous return). A thermometer is also fitted to the tube, to note the temperature of blood., A third mercury manometer is connected to the, inferior vena cava. It is used to determine the venous, pressure. A cardiometer is fitted to the ventricle. This, cardiometer is connected to a recording device like, Marey tambour or polygraph, to record the ventricular, volume changes., Pulmonary circulation is kept intact for continuous, oxygenation of blood., , USES OF HEART-LUNG PREPARATION, Thus, in this set up, the heart works as an isolated organ., So, the effects of various factors can be demonstrated, on the activities of heart, like heart rate, ventricular, volume and cardiac output.
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Chapter 99 t Heart-lung Preparation 583, , FIGURE 99.1: Heart-lung preparation., SVC = Superior vena cava, IVC = Inferior vena cava, PA = Pulmonary artery, PV = Pulmonary vein., , Examples, 1. When venous return decreases, stroke volume, decreases, 2. When venous return increases, stroke volume, increases, 3. When resistance increases, cardiac output, decreases, 4. When resistance decreases, cardiac output, increases, , 5. Heart-lung preparation is also used to record two, types of cardiac function curves:, i. Cardiac output curves, ii. Venous return curves., Though the cardiac function curves are obtained in, experiments using the animals, these curves represent, the functions of the ventricles in human heart also, (Chapter 100).
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Cardiac Function Curves, , Chapter, , 100, , INTRODUCTION, CARDIAC OUTPUT CURVES, , , , , NORMAL CARDIAC OUTPUT CURVES, FACTORS AFFECTING CARDIAC OUTPUT CURVES, EFFECT OF EXTRACARDIAC PRESSURE ON CARDIAC OUTPUT CURVE, , VENOUS RETURN CURVES, ANALYSIS OF CARDIAC FUNCTION CURVES, , , COUPLING OF CARDIAC AND VASCULAR FUNCTIONS, , INTRODUCTION, Cardiac function curves are Frank-Starling curves,, which demonstrate the capacity of ventricles to pump, blood and to maintain blood circulation throughout, the body. Most of the cardiac function curves are, obtained from animal experiments, by using heart-lung, preparation. However, these curves are considered to, represent the functions of ventricles in human heart., Cardiac function curves are of two types:, 1. Cardiac output curves, 2. Venous return curves., , CARDIAC OUTPUT CURVES, Cardiac output curves are the curves that show the, relationship between cardiac output and right atrial, pressure. Right atrial pressure, in turn, depends upon, venous return., NORMAL CARDIAC OUTPUT CURVES, Normally, left ventricular output is 5 L/minute, when, the pressure in right atrium is 2 mm Hg. When the, atrial pressure rises between 4 and 8 mm Hg, the left, ventricular output also increases. It increases to about, two and a half times of normal (basal) output, i.e. the, output increases to about 13 to 14 L/minute. This is the, maximum limit for increase in cardiac output. Further, , increase in right atrial pressure does not increase, the ventricular output and the curve shows a plateau, (Fig. 100.1)., Right ventricular output is 5 L/minute, when the right, atrial pressure is zero. This reaches the maximum, i.e., 13 to 14 L/minute when the atrial pressure increases, between 2 and 4 mm Hg (Fig. 100.1)., Thus, the cardiac output curves demonstrate that, cardiac output is directly proportional to atrial pressure, up to a certain extent (as explained above)., Plateau of the curve shows that the heart can, control the output by itself if the atrial pressure rises, beyond +8 mm Hg. It is due to the fact that in normal, conditions, venous return is decreased when atrial, pressure raises above +8 mm Hg., FACTORS AFFECTING CARDIAC, OUTPUT CURVES, Shifting of cardiac output curve to left indicates increase, in cardiac output and shifting to right indicates decrease, in cardiac output. The conditions which shift the cardiac, output curve to left or right are discussed below:, Shift to Left, When there is an abnormal increase in the functioning of, the heart (hypereffective heart), the cardiac output curve, is shifted to left, indicating increase in cardiac output.
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Chapter 100 t Cardiac Function Curves 585, EFFECT OF EXTRACARDIAC PRESSURE, ON CARDIAC OUTPUT CURVE, Extracardiac pressure is the pressure outside the heart., Intrapleural pressure is the major extracardiac pressure., When it increases above the normal level, i.e. from –6, to –2 mm Hg or becomes positive, the venous return, decreases, resulting in decrease in cardiac output. Cardiac output curve is shifted to right. It happens in opening, of thoracic cage and in positive pressure breathing., When the intrapleural pressure decreases, i.e., when it becomes more negative, the venous return, increases and the cardiac output also increases. The, curve is shifted towards left. It is common in negative, pressure breathing., , Cardiac Tamponade, , FIGURE 100.1: Normal cardiac output curves, , Conditions when shift to left occurs, 1. Combined stimulation of sympathetic and the parasympathetic nerves supplying the heart: It causes, hyperexcitation of the heart, resulting in increased, rate and force of contraction. The cardiac output, increases up to 25 L/minute (i.e. the plateau is shifted, to left). Increase in output is about twice the maximum, output in normal conditions (13 to 14 L/minute)., 2. Hypertrophy of heart: It increases cardiac output up, to 10 to 19 L/minute. It is because of increase in, force of contraction., 3. Excitation (by cardiac nerves) of the heart along, with hypertrophy of the ventricles: In this condition,, the cardiac output is elevated above 35 L/minute., It occurs in Marathon runners. Increase in cardiac, output is an important factor for prolonged running, time of Marathon runners., Shift to Right, When the functioning of heart decreases (hypoeffective, heart), cardiac output curve is shifted to right, indicating, decrease in cardiac output., Conditions when shift to right occurs, 1. Stimulation of parasympathetic nerve fibers of the, heart, 2. Inhibition of sympathetic nerves to heart, 3. Myocardial infarction, 4. Diseases of the valves in the heart, 5. Congenital heart diseases., , Cardiac tamponade is the mechanical compression of, heart due to accumulation of fluid in pericardial space., In addition to intrapleural pressure, accumulation of fluid, in pericardial space also increases the extracardiac, pressure and compresses the heart. In cardiac, tamponade, the cardiac output decreases and output, curve is shifted to right., , VENOUS RETURN CURVES, Venous return curves are the curves which demonstrate, the relationship between venous return (blood flow in, vascular system) and right atrial pressure. Venous, return curves are also called systemic vascular function, curves., , Normally, 5 L of blood returns to heart every, minute. When right atrial pressure increases, venous, return decreases due to backpressure. When venous, return decreases, the cardiac output also decreases, (Fig. 100.2)., , ANALYSIS OF CARDIAC, FUNCTION CURVES, Relation of cardiac output and venous return with right, atrial pressure is determined when cardiac output, curves and venous return curves are merged together, (Fig. 100.3)., COUPLING OF CARDIAC, AND VASCULAR FUNCTIONS, Cardiac output represents cardiac function and venous, return represents vascular function. Coupling or merging, of cardiac output (cardiac function) curves and venous, return (vascular function) curves shows that when, venous return is normal (5 L/minute), the cardiac output, as well as the right atrial pressure are normal.
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586 Section 8 t Cardiovascular System, , FIGURE 100.2: Venous return curve, , FIGURE 100.3: Analysis of cardiac function curves, , Relation between cardiac output and venous return, under normal conditions is represented by (A). When, the venous return increases (B), the cardiac output also, , increases along with increase in right atrial pressure., Thus, any factor that alters venous return alters the, cardiac output also.
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Chapter, , Heart Rate, , 101, , HEART RATE, , , , , NORMAL HEART RATE, TACHYCARDIA, BRADYCARDIA, , REGULATION OF HEART RATE, VASOMOTOR CENTER – CARDIAC CENTER, , , , , VASOCONSTRICTOR AREA, VASODILATOR AREA, SENSORY AREA, , MOTOR (EFFERENT) NERVE FIBERS TO HEART, , , , PARASYMPATHETIC NERVE FIBERS, SYMPATHETIC NERVE FIBERS, , SENSORY (AFFERENT) NERVE FIBERS FROM HEART, FACTORS AFFECTING VASOMOTOR CENTER – REGULATION OF VAGAL TONE, , , , , , , , , IMPULSES FROM HIGHER CENTERS, IMPULSES FROM RESPIRATORY CENTERS, IMPULSES FROM BARORECEPTORS, IMPULSES FROM CHEMORECEPTORS, IMPULSES FROM RIGHT ATRIUM, IMPULSES FROM OTHER AFFERENT NERVES, BEZOLD-JARISCH REFLEX, , HEART RATE, NORMAL HEART RATE, Normal heart rate is 72/minute. It ranges between 60, and 80 per minute., TACHYCARDIA, Tachycardia is the increase in heart rate above 100/, minute., Physiological Conditions when, Tachycardia Occurs, 1. Childhood, , 2. Exercise, 3. Pregnancy, 4. Emotional conditions such as anxiety., Pathological Conditions when, Tachycardia Occurs, 1., 2., 3., 4., 5., 6., 7., , Fever, Anemia, Hypoxia, Hyperthyroidism, Hypersecretion of catecholamines, Cardiomyopathy, Diseases of heart valves.
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588 Section 8 t Cardiovascular System, BRADYCARDIA, , Areas of Vasomotor Center, , Bradycardia is the decrease in heart rate below 60/, minute., , Vasomotor center is formed by three areas:, 1. Vasoconstrictor area, 2. Vasodilator area, 3. Sensory area., , Physiological Conditions when, Bradycardia Occurs, 1. Sleep, 2. Athletes., , VASOCONSTRICTOR AREA –, CARDIOACCELERATOR CENTER, Situation, , Pathological Conditions when, Bradycardia Occurs, 1., 2., 3., 4., 5., 6., 7., , Hypothermia, Hypothyroidism, Heart attack, Congenital heart disease, Degenerative process of aging, Obstructive jaundice, Increased intracranial pressure., , Vasoconstrictor area is situated in the reticular formation, of medulla in floor of IV ventricle and it forms the lateral, portion of vasomotor center. It is otherwise known as, pressor area or cardioaccelerator center., Function, Vasoconstrictor area increases the heart rate by sending, accelerator impulses to heart, through sympathetic, nerves. It also causes constriction of blood vessels. Stimu, lation of this center in animals increases the heart rate and, its removal or destruction decreases the heart rate., , Drugs which Induce Bradycardia, 1. Beta blockers, 2. Channel blockers, 3. Digitalis and other antiarrhythmic drugs., , REGULATION OF HEART RATE, Heart rate is maintained within normal range constantly., It is subjected for variation during normal physiological, conditions such as exercise, emotion, etc. However,, under physiological conditions, the altered heart rate, is quickly brought back to normal. It is because of the, perfectly tuned regulatory mechanism in the body., Heart rate is regulated by the nervous mechanism,, which consists of three components:, A. Vasomotor center, B. Motor (efferent) nerve fibers to the heart, C. Sensory (afferent) nerve fibers from the heart., , VASOMOTOR CENTER –, CARDIAC CENTER, Vasomotor center is the nervous center that regulates the, heart rate. It is the same center in brain, which regulates, the blood pressure. It is also called the cardiac center., Vasomotor center is bilaterally situated in the, reticular formation of medulla oblongata and lower part, of pons., , Control, Vasoconstrictor area is under the control of hypothalamus and cerebral cortex., VASODILATOR AREA –, CARDIOINHIBITORY CENTER, Situation, Vasodilator area is also situated in the reticular formation, of medulla oblongata in the floor of IV ventricle. It forms, the medial portion of vasomotor center. It is also called, depressor area or cardioinhibitory center., Function, Vasodilator area decreases the heart rate by sending, inhibitory impulses to heart through vagus nerve. It also, causes dilatation of blood vessels. Stimulation of this, area in animals with weak electric stimulus decreases, the heart rate and stimulation with a strong stimulus, stops the heartbeat. When this area is removed or, destroyed, heart rate increases., Control, Vasodilator area is under the control of cerebral cortex, and hypothalamus. It is also controlled by the impulses, from baroreceptors, chemoreceptors and other sensory, impulses via afferent nerves.
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Chapter 101 t Heart Rate 589, SENSORY AREA, , Origin, , Situation, Sensory area is in the posterior part of vasomotor center,, which lies in nucleus of tractus solitarius in medulla, and pons., , Parasympathetic nerve fibers supplying heart arise from, the dorsal nucleus of vagus. This nucleus is situated, in the floor of fourth ventricle in medulla oblongata and, is in close contact with vasodilator area., Distribution, , Function, Sensory area receives sensory impulse via glosso, pharyngeal nerve and vagus nerve from periphery,, particularly, from the baroreceptors. In turn, this area, controls the vasoconstrictor and vasodilator areas., , MOTOR (EFFERENT) NERVE, FIBERS TO HEART, Heart receives efferent nerves from both the divisions of, autonomic nervous system. Parasympathetic fibers arise, from the medulla oblongata and pass through vagus, nerve. Sympathetic fibers arise from upper thoracic (T1, to T4) segments of spinal cord (Fig. 101.1)., , Preganglionic parasympathetic nerve fibers from, dorsal nucleus of vagus reach the heart by passing, through the main trunk of vagus and cardiac branch, of vagus. After reaching the heart, preganglionic fibers, terminate on postganglionic neurons. Postganglionic, fibers from these neurons innervate heart muscle., Most of the fibers from right vagus terminate in, sinoatrial (SA) node. Remaining fibers supply the atrial, muscles and atrioventricular (AV) node. Most of the, fibers from left vagus supply AV node and some fibers, supply the atrial muscle and SA node., Ventricles do not receive the vagus nerve supply., Few fibers are located in the bases of ventricles, but the, functions of these nerve fibers are not known., , PARASYMPATHETIC NERVE FIBERS, Parasympathetic nerve fibers are the cardioinhibitory, nerve fibers. These nerve fibers reach the heart through, the cardiac branch of vagus nerve., , Function, Vagus nerve is cardioinhibitory in function and carries, inhibitory impulses from vasodilator area to the heart., , FIGURE 101.1: Nerve supply to heart
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590 Section 8 t Cardiovascular System, Vagal Tone, Vagal tone is the continuous stream of inhibitory impulses, from vasodilator area to heart via vagus nerve. Heart, rate is kept under control because of vagal tone., These impulses reach the heart and exert inhibitory, effect on heart. Heart rate is inversely proportional to, vagal tone. In experimental animals (dog), removal of, vagal input (by sectioning vagus) increases the heart, rate. This proves the existence of vagal tone. Under, resting conditions, vagal tone dominates sympathetic, tone (see below)., Impulses from different parts of the body regulate, the heart rate through vasomotor center, by altering the, vagal tone. Vagal tone is also called cardioinhibitory, tone or parasympathetic tone., Effect of Stimulation of Vagus Nerve, Effect of stimulation of right vagus nerve –, Vagal escape, Right vagus supplies mainly SA node. Stimulation of, right vagus in experimental animals such as dog, with, a weak stimulus causes reduction in heart rate and, force of contraction. Stimulation with strong stimulus, causes stoppage of heart due to inhibition of SA node., If the stimulus is continued for some time, the ventricle, starts beating; but the rate of contraction is slower than, before. This is because of vagal escape., Vagal escape refers to escape of ventricle from, inhibitory effect of vagal stimulation. If stimulation of, vagus nerve is stopped, heart starts beating normally, (Fig. 101.2)., Cause for vagal escape, Stimulation of right vagus stops the heartbeat due to, inhibition of SA node and atria. However, ventricles, are not supplied by vagus. So, the ventricles are not, inhibited by vagal stimulation. Because of this, when, stoppage of heart beat is continued for some time (by, vagal stimulation), a part of ventricular musculature, becomes pacemaker and starts producing impulses. It, results in contraction of ventricles, which is called vagal, escape., Thus, vagal escape includes only ventricular, contractions. However, the rhythmicity of ventricular, muscle is less and it is about 20/minute., Effect of stimulation of left vagus nerve – heart block, Left vagus supplies mainly the AV node. Stimulation of, left vagus in dog with a weak stimulus causes a slight, , FIGURE 101.2: Effect of vagal stimulation on frog heart, , reduction in rate of ventricular contraction. Stimulation, of left vagus causes inhibition of AV node. Because of, inhibition of AV node, some of the impulses from SA node, are not conducted to ventricles. This is called the partial, heart block. The ratio between atrial contraction and, ventricular contraction is 2 : 1, 3 : 1 or 4 : 1, depending, upon the strength of stimulus., Stimulation of left vagus with strong stimulus causes, stoppage of ventricular contraction, which is called, complete heart block. This is because of the complete, inhibition of AV node. The prolongation of stimulation, causes idioventricular rhythm, which is different from, the rhythm of atrial contraction., Mode of Action of Vagus Nerve, Vagus nerve inhibits the heart by secreting the, neurotransmitter substance known as acetylcholine., SYMPATHETIC NERVE FIBERS, Sympathetic nerve fibers supplying the heart have, cardioacceleratory function., Origin, Preganglionic fibers of the sympathetic nerves to heart, arise from lateral gray horns of the first 4 thoracic (T1 to, T4) segments of the spinal cord. These segments of the, spinal cord receive fibers from vasoconstrictor area of, vasomotor center., Course and Distribution, Preganglionic fibers reach the superior, middle and, inferior cervical sympathetic ganglia situated in, the sympathetic chain. Inferior cervical sympathetic, ganglion fuses with first thoracic sympathetic ganglion,, forming stellate ganglion. From these ganglia, the, postganglionic fibers arise.
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Chapter 101 t Heart Rate 591, Postganglionic fibers form three nerves:, 1. Superior cervical sympathetic nerve, which inner, vates larger arteries and base of the heart, 2. Middle cervical sympathetic nerve, which supplies, the rest of the heart, 3. Inferior cervical sympathetic nerve, which serves as, sensory (afferent) nerve from the heart., Function, Sympathetic nerves are cardioaccelerators in func, tion and carry cardioaccelerator impulses from, vasoconstrictor area to the heart., Sympathetic Tone, Sympathetic tone or cardioaccelerator tone is, the continuous stream of impulses produced by, the vasoconstrictor area. Impulses pass through, sympathetic nerves and accelerate the heart rate., Under normal conditions, the vagal tone is, dominant over sympathetic tone. Whenever vagal tone, is reduced or abolished, the sympathetic tone becomes, powerful. It is generally believed that the sympathetic, tone does not play an important role in the regulation of, cardiac function under resting physiological conditions., However, it plays a definite role in increasing the heart, rate during emergency conditions., Rate of contraction of a completely denervated, heart of dog is higher than the rate of an innervated, heart in resting conditions. This shows that under, resting conditions, the vagal tone is dominant over, sympathetic tone., , FACTORS AFFECTING VASOMOTOR, CENTER – REGULATION OF VAGAL TONE, Vasomotor center regulates the cardiac activity by, receiving impulses from different sources in the body., After receiving the impulses from different sources, the, vasodilator area alters the vagal tone and modulates, the activities of the heart., Various sources from which the impulses reach the, vasomotor center:, 1. IMPULSES FROM HIGHER CENTERS, Vasomotor center is mainly controlled by the impulses from, higher centers in cerebral cortex and hypothalamus., Cerebral Cortex, Area 13 in cerebral cortex is concerned with emotional, reactions of the body. During emotional conditions,, this area sends inhibitory impulses to the vasodilator, area. This causes reduction in vagal tone, leading to, increase in heart rate., Hypothalamus, Hypothalamus influences the heart rate via vasomotor, center. Stimulation of posterior and lateral hypothalamic, nuclei causes tachycardia. Stimulation of preoptic and, anterior nuclei causes bradycardia., 2. IMPULSES FROM RESPIRATORY CENTERS, , noradrenaline., , In forced breathing, heart rate increases during, inspiration and decreases during expiration. This, variation is called respiratory sinus arrhythmia. This, is common in some children and in some adults even, during quiet breathing., Sinus arrhythmia is due to the alteration of vagal, tone because of impulses arising from respiratory, centers during inspiration. These impulses inhibit the, vasodilator area, resulting in decreased vagal tone and, increased heart rate. During expiration, the respiratory, center stops sending impulses to vasodilator center., Now, vagal tone increases, leading to decrease in, heart rate., , SENSORY (AFFERENT) NERVE, FIBERS FROM HEART, , 3. IMPULSES FROM BARORECEPTORS –, MAREY REFLEX, , Afferent (sensory) nerve fibers from the heart pass, through inferior cervical sympathetic nerve. These, nerve fibers carry sensations of stretch and pain from, the heart to brain via spinal cord., , Baroreceptors, , Effect of Stimulation of Sympathetic Nerves, Stimulation of sympathetic nerves increases the rate, and force of contraction of heart. The effect depends, upon the strength of stimulus., Mode of Action of Sympathetic Nerves, Cardioacceleration by sympathetic stimulation is, due to the release of neurotransmitter substance,, , Baroreceptors are the receptors which give response, to change in blood pressure. These receptors are also, called pressoreceptors.
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592 Section 8 t Cardiovascular System, Situation, Depending upon the situation, baroreceptors are divided, into two types:, 1. Carotid baroreceptors, situated in carotid sinus,, which is present in the wall of internal carotid artery, near the bifurcation of common carotid artery., 2. Aortic baroreceptors, situated in the wall of arch of, aorta., , area, which in turn increases the vagal tone, leading to, decrease in heart rate (Fig. 101.4). Marey reflex includes, aortic reflex and carotid sinus reflex., When pressure is less, the baroreceptors are not, stimulated. So, no impulses go to nucleus of tractus, solitarius. There are no inhibitory impulses to the heart, and heart rate is not decreased. Thus, the heart rate is, inversely proportional to blood pressure., , Nerve Supply, , Marey law, , Carotid baroreceptors are supplied by Hering nerve,, which is the branch of glossopharyngeal (IX cranial), nerve. Aortic baroreceptors are supplied by aortic, nerve, which is a branch of vagus (X cranial) nerve, (Fig. 101.3)., Nerve fibers from the baroreceptors reach the, nucleus of tractus solitarius, which is situated adjacent, to vasomotor center in medulla oblongata., , According to Marey law, the pulse rate (which represents, heart rate) is inversely proportional to blood pressure., Baroreceptors induce the Marey reflex only during, resting conditions. So, in many conditions such as, exercise, there is an increase in both blood pressure, and heart rate., , Function – Marey Reflex, , Chemoreceptors, , Baroreceptors regulate the heart rate through Marey, reflex. Stimulus for this reflex is increase in blood, pressure., Marey reflex is a cardioinhibitory reflex that, decreases heart rate when blood pressure increases., Whenever blood pressure increases, the aortic and, carotid baroreceptors are stimulated and stimulatory, impulses are sent to nucleus of tractus solitarius via, Hering nerve and aortic nerve (afferent nerves). Now,, the nucleus of tractus solitarius stimulates vasodilator, , Chemoreceptors are receptors giving response to, change in chemical constituents of blood, particularly, oxygen, carbon dioxide and hydrogen ion concentration., , FIGURE 101.3: Nerve supply to baroreceptors, and chemoreceptors, , 4. IMPULSES FROM CHEMORECEPTORS, , FIGURE 101.4: Marey (cardioinhibitory) reflex
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Chapter 101 t Heart Rate 593, Situation, Peripheral chemoreceptors are situated in the carotid, body and aortic body, adjacent to baroreceptors., Structure, Chemoreceptors are made up of two types of cells, type, I or glomus cells and type II or sustentacular cells., Glomus cells have afferent nerve endings, which are, stimulated by hypoxia. Type II cells are glial cells and, provide support for type I cells., Nerve Supply, Chemoreceptors in the carotid body are supplied by, Hering nerve, which is the branch of glossopharyngeal, , nerve. Chemoreceptors in the aortic body are supplied, by aortic nerve which is the branch of vagus nerve, (Fig. 101.3)., Function, Whenever there is hypoxia, hypercapnea and, increased hydrogen ions concentration in the blood, the, chemoreceptors are stimulated and inhibitory impulses, are sent to vasodilator area. Vagal tone decreases and, heart rate increases. Chemoreceptors play a major role, in maintaining respiration than the heart rate., Sinoaortic Mechanism and Buffer Nerves, Sinoaortic mechanism is the mechanism of baro, receptors and chemoreceptors in carotid and aortic, regions, that regulates heart rate, blood pressure and, respiration. The nerves supplying these receptors are, called buffer nerves., 5. IMPULSES FROM RIGHT ATRIUM –, BAINBRIDGE REFLEX, , FIGURE 101.5: Bainbridge (cardioaccelerator) reflex, , nerve to vasodilator area of vasomotor center. Vasodilator, , area is inhibited, resulting in decrease in vagal tone and, increase in heart rate (Fig. 101.5)., 6. IMPULSES FROM OTHER, AFFERENT NERVES, Stimulation of sensory nerves produces varying effects., Examples:, i. Stimulation of receptors in nasal mucous, membrane causes bradycardia. Impulses from, nasal mucous membrane pass via the branches, of V cranial nerve and decrease the heart rate., ii. Most of the painful stimuli cause tachycardia, and some cause bradycardia. Impulses are, transmitted via pain nerve fibers (Fig. 101.6)., , Bainbridge reflex is a cardioaccelerator reflex that, increases the heart rate when venous return is increased., Since this reflex arises from right atrium, it is also called, , 7. BEZOLD-JARISCH REFLEX, , Increase in venous return causes distention of right, atrium and stimulation of stretch receptors, situated in, the wall of right atrium. Stretch receptors, in turn, send, inhibitory impulses through inferior cervical sympathetic, , Bezold-Jarisch reflex is the reflex characterized by, bradycardia and hypotension, caused by stimulation of, chemoreceptors present in the wall of left ventricles by, substances such as alkaloids. It is also called coronary, , right atrial reflex.
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594 Section 8 t Cardiovascular System, , FIGURE 101.6: Factors regulating vagal tone and heart rate, , chemoreflex. Vagal fibers form the afferent and efferent, pathways of this reflex., , Conditions when Bezold-Jarisch Reflex Occurs, Bezold-Jarisch reflex is a pathological reflex and it, does not occur in physiological conditions., , 1., 2., 3., 4., 5., , Conditions when this reflex occurs:, Myocardial infarction, Administration of thrombolytic agents, Hemorrhage, Aortic stenosis, Syncope.
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Chapter, , Hemodynamics, , 102, , INTRODUCTION, MEAN VOLUME OF BLOOD FLOW, , , , , , , DEFINITION AND FORMULA, IMPORTANCE, METHODS OF STUDY, TYPES OF BLOOD FLOW, FACTORS DETERMINING VOLUME OF BLOOD FLOW, , HAGEN-POISEUILLE EQUATION, WINDKESSEL EFFECT, VELOCITY OF BLOOD FLOW, , , , , , , DEFINITION, MEAN VELOCITY OF BLOOD FLOW, METHODS OF STUDY, FACTORS MAINTAINING VELOCITY, PHASIC CHANGES IN THE VELOCITY OF BLOOD FLOW, , CIRCULATION TIME, , , , , , , DEFINITION, MEASUREMENT OF CIRCULATION TIME, TYPICAL CIRCULATION TIMES, TOTAL CIRCULATION TIME AND HEARTBEAT, CONDITIONS ALTERING CIRCULATION TIME, , LOCAL REGULATION OF BLOOD FLOW – AUTOREGULATION, , , , , , INTRODUCTION, ROLE OF PRESSURES IN AUTOREGULATION, THEORIES OF AUTOREGULATION, AUTOREGULATION IN SOME VITAL ORGANS, , INTRODUCTION, Dynamics means study of motion. Hemodynamics, , refers to the study of movement of blood through, circulatory system., Major function of cardiovascular system is to pump, the blood and to circulate it through different parts of, the body. It is essential for the maintenance of pressure, and other physical factors within the blood vessels, so, that the volume of blood supplied to different parts of, , the body is adequate. Circulatory system is designed for, carrying out all these actions., , MEAN VOLUME OF BLOOD FLOW, DEFINITION AND FORMULA, Mean volume of blood flow is the volume of blood which, flows into the region of circulatory system in a given unit, of time. It is the product of mean velocity and the cross-
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596 Section 8 t Cardiovascular System, sectional area of the vascular bed., Q=V×A, Where,, Q = Quantity of blood, V = Velocity of blood flow, A = Cross-sectional area of the blood vessel., IMPORTANCE, In terms of transport of foodstuffs and oxygen to the, tissues and waste products away from the tissues,, mean volume of blood flow is of greater physiological, importance than linear velocity., METHODS OF STUDY, 1. By Using Flowmeters, Different types of flowmeters are described in Chapter, 98., 2. By Using Plethysmograph, Plethysmograph is an instrument used for measuring, the volume of an enclosed organ., 3. By Venous Occlusion Plethysmography, In this, the venous outflow from an organ is stopped by, clamping the vein, without disturbing the artery. Blood, flow into the organ causes a corresponding increase, in its volume for the first few seconds. This increase in, volume is recorded graphically. Amount of blood flow is, determined by proper calibration of the graph., 4. By Fick Principle, Fick principle is explained in the measurement of cardiac, output in Chapter 98., TYPES OF BLOOD FLOW, Blood flow through a blood vessel is of two types:, 1. Streamline or laminar flow, 2. Turbulent flow., , does not produce any sound within the vessel (Fig., 102.1). Streamline flow occurs only at velocities up to, a critical level., 2. Turbulent Flow, Turbulent flow is the noisy flow. When the velocity, of blood flow increases above critical level, the flow, becomes turbulent. Turbulent flow creates sounds., Reynolds number, Critical velocity at which the flow becomes turbulent is, known as Reynolds number., , Formula to determine Reynolds number:, NR =, NR, P, D, V, η, , =, =, =, =, =, , PDV, η, Reynolds number, Density of the blood, Diameter of the vessel, Velocity of the flow, Viscosity of the blood, , FACTORS DETERMINING VOLUME, OF BLOOD FLOW, Volume of blood flow is determined by five factors:, 1. Pressure gradient, 2. Resistance to blood flow, 3. Viscosity of blood, 4. Diameter of blood vessels, 5. Velocity of blood flow., 1. Pressure Gradient, Volume of blood flowing through any blood vessel is, directly proportional to the pressure gradient. Pressure, , gradient is the pressure difference between the two, ends of the blood vessel., , 1. Streamline Flow, Streamline flow is a silent flow. Within the blood vessel,, a very thin layer of blood is in contact with the vessel, wall. It does not move or moves very slowly. Next layer, within the vessel has a low momentum. Next layer of, blood has a slightly higher momentum. Gradually, the, momentum increases in the inner layers, so that the, momentum is greatest in the center of the stream., This type of flow is known as streamline flow and it, , FIGURE 102.1: Streamline flow and turbulent flow
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Chapter 102 t Hemodynamics 597, Formula to determine pressure gradient, Pressure gradient = P1 – P2, Where,, P1 = Pressure at proximal end of the vessel, P2 = Pressure at distal end of the vessel., Maximum pressure gradient exists between the, aorta and the inferior vena cava. The pressure in aorta, is 120 mm Hg and the pressure in inferior vena cava is, 0 mm Hg. So, the pressure gradient is 120 – 0 = 120, mm Hg. Pressure gradient in different areas of vascular, bed is given in Table 102.1., 2. Resistance to Blood Flow, (Peripheral Resistance), Volume of blood flow is inversely proportional to, the resistance. Resistance is the friction, tension or, hindrance, against which the blood has to flow. Peripheral, resistance means the resistance offered to blood flow, in peripheral blood vessels. Though resistance exists in, all the blood vessels to some extent, it is remarkable in, the peripheral vessels, particularly the arterioles., Determinants of peripheral resistance, i. Radius of blood vessels, ii. Pressure gradient, iii. Viscosity of blood., Peripheral resistance is inversely related to radius, of the blood vessel, i.e. lesser the radius, more will be, the resistance. Radius of the arterioles is very less. It is, because the arterioles remain partially constricted all the, time due to sympathetic tone. So, the resistance is more., Hence, the arterioles are called resistant vessels., , Formula to determine resistance, Resistance =, , =, , Pressure gradient, Volume of blood flow, P1 – P2, Q, , 3. Viscosity of Blood, Volume of blood flow is inversely proportional to the, viscosity of blood. Viscosity is the friction of blood against, the wall of the blood vessel. Isaac Newton described, viscosity as the internal friction or lack of slipperiness., Viscosity influences the blood flow through resistance., Factors determining viscosity, RBC count is the main factor which determines the, viscosity of the blood. Another factor determining, viscosity is plasma protein, mainly albumin., When hemoconcentration occurs as in case of, burns or in polycythemia, the viscosity increases and, the velocity of blood flow decreases, so the volume of, blood reaching the organ is decreased., 4. Diameter of Blood Vessels, Volume of blood flow is directly proportional to the, diameter of the blood vessels. When the diameter of a, segment of blood vessel is considered, the aorta has the, maximum diameter and capillary has got the minimum, diameter. But, in circulation, the diameter of the vessel, is considered in relation to the cross-sectional area, through which the blood flows., , TABLE 102.1: Pressure gradient in different areas of vascular bed, P1, (mm Hg), , P2, (mm Hg), , Pressure gradient, (mm Hg), , Between aorta and vena cava, , 120, , 0, , 120, , Between two ends of aorta, , 120, , 100, , 20, , Between beginning of arteries and end of arterioles, , 100, , 30, , 70, , Between arterial and venous ends of capillaries, , 30, , 15, , 15, , Between two ends of venules, , 15, , 10, , 5, , Between two ends of veins, , 10, , 0, , 10, , 0, , –2, , –2, , Blood vessels, , Between two ends of vena cava, , P1 = Pressure at proximal end of the blood vessel, P2 = Pressure at distal end of the blood vessel, Pressure gradient = P1 – P2.
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598 Section 8 t Cardiovascular System, Cross-sectional area is progressively increased as, the arteries ramify and as the distance from the heart, is increased. Cross-sectional area of each branch is, smaller, but the sum of the cross-sectional areas of all, the branches is always greater than that of the parent, vessel. In this way, the aorta has got less cross-sectional, area of 4 cm2, compared to that of capillaries, which is, 2,500 cm2., But, the cross-sectional area is subjected to variations, under physiological and pathological conditions. Diameter of the aorta depends upon the elasticity of the, wall and its recoiling tendency helps in maintaining the, flow and pressure. Diameter of the arterioles depends, upon the sympathetic tone., 5. Velocity of Blood Flow, Volume of blood flow is directly proportional to the, velocity of blood flow. Velocity of blood flow is the rate, at which blood flows through a particular region. It is, described later in this chapter., , HAGEN-POISEUILLE EQUATION, Hagen and Poiseuille have worked on dynamics, extensively. Equation which explains the relationship, between different variables of dynamics, is named, after them. Variables of dynamics are applied to, hemodynamics also., According to Hagen-Poiseuille equation, volume, (Q) of any fluid flowing through a rigid tube is:, 1. Directly proportional to pressure gradient (P1 – P2), 2. Directly proportional to the fourth power of radius, (r4), 3. Inversely proportional to the length of the tube (L)., Thus, Q = K, , (P1 – P2) × r4, , L, K is the constant for fluid flowing at a temperature., It is directly proportional to temperature of the fluid., Viscosity of the fluid is also affected by the temperature., Viscosity is inversely proportional to temperature of, the fluid. Therefore in the equation, the constant ‘K’ is, expressed as the reciprocal of viscosity (η)., So, Q =, , (P1 – P2 ) × r4, L×η, , Volume of flow of fluid is always expressed in a, given unit of time. π/8 is the arithmetic value derived, while determining volume of fluid flowing in a given unit, of time. So, the equation has to be rewritten as:, , Q, , =, , =, Thus, Q =, , (P1 – P2) × r4, L × η × π/8, (P1 – P2) × πr4, 8 (L × η), (P1 – P2) πr4, 8 (L × η), , WINDKESSEL EFFECT, Windkessel effect is the recoiling effect of blood, vessels that converts the pulsatile flow of blood into a, continuous flow. Blood vessels showing the windkessel, effect are known as windkessel vessels., Mean velocity of the blood that flows through the, aorta is more than 50 cm/second, but it is not constant., During systole, it increases up to 120 cm/second and, during diastole, it becomes almost negative. This, variation is noticed even in the larger arteries., During systole, velocity of blood flow reaches, maximum, because of the force created by contraction, of the heart. Therefore, the maximum volume of blood, is pumped into the aorta. During diastole, this force, is absent and the volume of blood entering the aorta, is zero. Thus, the flow of blood into the aorta is not, continuous. This type of flow is called pulsatile flow., However, the flow of blood through other blood, vessels is continuous. It is because of the behavioral, pattern of aorta and to a little extent, the behavioral, pattern of larger arteries. During systole, the aorta is, completely dilated and during diastole, it recoils. The, elastic recoiling of this vessel creates the continuous, momentum of blood. So, the pulsatile flow of blood is, converted into a continuous flow., This effect was named as windkessel effect by Otto, Frank, in 1899. Windkessel is a German word used for, an ‘elastic reservoir’., Thus, the windkessel vessels play an important role, in maintaining the continuous flow of blood through the, circulatory tree by acting as a second pump, the first, pump being the heart., , VELOCITY OF BLOOD FLOW, DEFINITION, Velocity of blood flow is the rate at which blood flows, through a particular region of the body. It mainly, depends upon the diameter or cross-sectional area of, blood vessel.
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Chapter 102 t Hemodynamics 599, MEAN VELOCITY OF BLOOD FLOW, IN DIFFERENT VESSELS, , PHASIC CHANGES IN THE VELOCITY, OF BLOOD FLOW, , Mean velocity (cm/second) of blood flow in different, blood vessels:, Large arteries : 50.00, Small arteries :, 5.00, Arterioles, :, 0.50, Capillaries, :, 0.05, Venules, :, 0.10, Small veins, :, 1.00, Large veins, :, 2.00, , Velocity of blood flow is altered according to the phases, of cardiac cycle. Blood flows in the large arteries at a, greater speed during systole than during diastole. In, common carotid artery, the velocity reaches 50 cm/sec, during systole and it is only 30 cm/sec during diastole., , METHODS OF STUDY, , Circulation time is the time taken by blood to travel, through a part or whole of the circulatory system., If a substance is injected into a vein, the time taken, by it to appear in the blood of the same vein or in the, corresponding vein on the opposite side shows the, total circulation time., Similarly, if the transit is from vein to the lungs, it, shows the circulation time through pulmonary circuit, and if it is from vein to capillaries, it shows the time for, flow through pulmonary circuit, left heart and arteries to, capillaries, i.e. the total circulation time minus the time, for venous return., , 1. By Using Flowmeters, Flowmeters are described in Chapter 98., 2. By Hemodromography, Hemodromography is a technique by which the velocity, of blood is continuously recorded., FACTORS MAINTAINING VELOCITY, Three factors are responsible for the maintenance of, the velocity of blood flow:, 1. Cardiac output, 2. Cross-sectional area of the blood vessel, 3. Viscosity of the blood., 1. Cardiac Output, Velocity of blood flow is directly proportional to cardiac, output. Increase in cardiac output leads to increase in, the velocity of blood flow in all parts of the circulation., 2. Cross-sectional Area of Blood Vessels, Velocity of blood flow is inversely proportional to the total, cross-sectional area of the vascular bed, through which, the blood circulates. Cross-sectional area increases, progressively as the arteries ramify. Cross-sectional, area of each branch is smaller, but the sum of the crosssectional areas of all the branches is always greater than, that of the parent vessel. So, velocity of blood flow is, decreased as the distance from the heart is increased., 3. Viscosity of Blood, Velocity of blood flow is inversely proportional to the, viscosity of blood. If viscosity is more, the velocity, of blood flow is reduced (See in Factors maintaining, volume of blood flow). It is because of the friction of, blood against arterial wall, which is more when viscosity, of blood is increased., , CIRCULATION TIME, DEFINITION, , MEASUREMENT OF CIRCULATION TIME, Circulation time is measured by introducing some, easily recognized substance into bloodstream and, determining the time when the substance appears at a, given point (end point) in the circulation., The injected substance must produce some, characteristic response at its end point, so that its, appearance could be easily recognized. Introduction, of the substance into circulation is done by injecting, through median cubital vein or directly into the heart., Substances used for Measuring, Circulation Time, 1. Histamine: Causes flushing of face due to, vasodilatation, 2. Dehydrocholine (20%): Gives a bitter taste when it, reaches the tongue, 3. Ether or acetone: Detectable in breath by smell, 4. Sodium cyanide (small dose): Causes hyperpnea, when it reaches the carotid artery (by acting on, baroreceptors), 5. Dye fluorescein: Identified at the end point by yellow, color; it is used for total circulation time, 6. Radioactive substances: Detected at various points, of the body by using an ionization chamber.
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600 Section 8 t Cardiovascular System, TYPICAL CIRCULATION TIMES, 1. Arm vein to arm vein (total circulation time): 25, seconds (22 to 28), determined by using dye, fluorescein, 2. Arm vein to face: 24 seconds, determined by using, histamine, 3. Arm vein to tongue: 11 seconds (8 to 16), determined, by using dehydrocholine, 4. Arm vein to lung (pulmonary circulatory time):, 6 seconds (4 to 6), determined by using ether or, acetone, 5. Arm vein to heart (shortest circulation time):, 4 seconds, determined by using radioactive, substances, 6. Arm vein to carotid artery: 14 seconds (12 to 15),, determined by using sodium cyanide., , LOCAL REGULATION OF BLOOD, FLOW – AUTOREGULATION, INTRODUCTION, Autoregulation means the regulation of blood flow to an, organ by the organ itself. It is defined as the intrinsic, ability of an organ to regulate a constant blood flow,, in spite of changes in the perfusion pressure (arterial, pressure – venous pressure)., Normally, a sudden increase or decrease in arterial, blood pressure momentarily increases or decreases the, blood flow. Local mechanisms start functioning and the, blood flow is brought to relatively normal level within few, minutes., Autoregulatory response is independent of neural, and hormonal influences. So, it is the intrinsic capacity, of the organ., , TOTAL CIRCULATION TIME AND HEARTBEAT, , ROLE OF PRESSURES IN AUTOREGULATION, , Number of heartbeat/total circulation time, however,, remains the same for human beings and all the animals,, i.e. about 30/total circulation time., , Perfusion Pressure and Effective, Perfusion Pressure, , CONDITIONS ALTERING CIRCULATION TIME, Circulation time is decreased when the velocity of, blood flow is increased and the circulation time is more, when the velocity is less., Conditions when Circulation Time, is Prolonged (Sluggish Blood Flow), 1. Myxedema: Due to decreased metabolic activity, 2. Polycythemia: Due to increased viscosity of blood, 3. Cardiac failure: Due to inability of the heart to pump, blood., Conditions when Circulation Time, is Shortened (Rapid Blood Flow), 1. Exercise: Due to increased cardiac activity and, vasodilatation, 2. Adrenaline administration: Due to increased cardiac, activity, 3. Hyperthyroidism: Due to increased metabolic, activity, 4. Anemia: Due to decreased blood volume and less, viscosity, 5. Decrease in peripheral resistance: Due to, vasodilatation., , Generally, the term perfusion pressure refers to balance, between the pressure in blood vessels on either side of, the organ, i.e. arterial pressure minus venous pressure, (PA – PV) across the organ., However, the blood flow to any organ or region of the, body depends up on the effective perfusion pressure., Effective perfusion pressure is the perfusion pressure, divided by resistance in the blood vessels., Formula to determine effective perfusion pressure, EFP =, EFP, PA, PV, R, , =, =, =, =, , PA – PV, R, Effective perfusion pressure, Arterial pressure, Venous pressure, Resistance, , But basically, the major factor that determines the, perfusion pressure and effective perfusion pressure is, the mean arterial pressure. The normal mean arterial, blood pressure is about 93 mm Hg. Usually, blood, flow through an organ is kept constant when the mean, arterial pressure increases up to 170 mm Hg or when it, falls till 60 mm Hg (the range varies slightly in different, organs). However, beyond this range, the autoregulation, fails and the blood flow is altered in relation to rise or, fall in pressure.
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Chapter 102 t Hemodynamics 601, THEORIES OF AUTOREGULATION, , 2. Metabolic Theory, , Autoregulation is explained by two theories:, 1. Myogenic theory, 2. Metabolic theory., , According to metabolic theory the normal blood flow is, maintained by the metabolic end products. Normally,, the flow of blood washes away the metabolic end, products. When the blood flow is reduced, there is, accumulation of metabolites. These metabolites dilate, the blood vessels and bring the blood flow back to, normal. Conversely, when blood flow increases, the, vasodilator metabolites are washed out of the tissues, quickly. It leads to vasoconstriction and the volume of, blood flow becomes normal., Common vasodilators of metabolic origin:, i. Adenosine, ii. Carbon dioxide, iii. Lactate, iv. Hydrogen., , 1. Myogenic Theory, According to this theory, the intrinsic contractile, property of the smooth muscle fibers present in the, blood vessels is responsible for autoregulation. It is, known that the sudden stretching of blood vessels, causes contraction of smooth muscle fibers present, in the wall of the vessels, particularly small arteries, and arterioles. So, when the arterial blood pressure, increases suddenly, the stretching of the blood vessels, immediately causes vasoconstriction and thereby, the, blood flow is controlled., Stretching of blood vessels due to increased, blood pressure increases the flow of calcium ions into, the cells from ECF. Calcium influx causes contraction, of smooth muscles in the blood vessels, leading to, vasoconstriction., On the other hand, when the blood pressure is, less, the stretching of blood vessels is less causing, vasodilatation and increase in blood flow., , AUTOREGULATION IN SOME VITAL ORGANS, Volume of blood flow is regulated by local mechanisms, in almost all the tissues of the body. However, autoregulation is more effective in some of the vital organs, like kidney (Chapter 51), heart (Chapter 108) and brain, (Chapter 109). Mechanism of autoregulation also varies, slightly in these organs.
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Arterial Blood Pressure, , Chapter, , 103, , DEFINITIONS AND NORMAL VALUES, , , , , , SYSTOLIC BLOOD PRESSURE, DIASTOLIC BLOOD PRESSURE, PULSE PRESSURE, MEAN ARTERIAL PRESSURE, , VARIATIONS, , , , PHYSIOLOGICAL VARIATIONS, PATHOLOGICAL VARIATIONS, , DETERMINANTS OF ARTERIAL BLOOD PRESSURE, , , , CENTRAL FACTORS, PERIPHERAL FACTORS, , REGULATION OF ARTERIAL BLOOD PRESSURE, NERVOUS MECHANISM, , , , , , VASOMOTOR CENTER, VASOCONSTRICTOR FIBERS, VASODILATOR FIBERS, MECHANISM OF ACTION OF VASOMOTOR CENTER, , RENAL MECHANISM, , , , BY REGULATION OF EXTRACELLULAR FLUID VOLUME, THROUGH RENIN-ANGIOTENSIN MECHANISM, , HORMONAL MECHANISM, , , , HORMONES WHICH INCREASE BLOOD PRESSURE, HORMONES WHICH DECREASE BLOOD PRESSURE, , LOCAL MECHANISM, , , , LOCAL VASOCONSTRICTORS, LOCAL VASODILATORS, , MEASUREMENT OF ARTERIAL BLOOD PRESSURE, , , , DIRECT METHOD, INDIRECT METHOD, , APPLIED PHYSIOLOGY, , , , HYPERTENSION, HYPOTENSION
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Chapter 103 t Arterial Blood Pressure 603, , DEFINITIONS AND NORMAL VALUES, , VARIATIONS, , Arterial blood pressure is defined as the lateral pressure, exerted by the column of blood on wall of arteries., The pressure is exerted when blood flows through the, arteries. Generally, the term ‘blood pressure’ refers to, arterial blood pressure., Arterial blood pressure is expressed in four different, terms:, 1. Systolic blood pressure, 2. Diastolic blood pressure, 3. Pulse pressure, 4. Mean arterial blood pressure., , Blood pressure is altered in physiological and pathologi, cal conditions. Systolic pressure is subjected for, variations easily and quickly and its variation occurs in, a wider range. Diastolic pressure is not subjected for, easy and quick variations and its variation occurs in a, narrow range., , SYSTOLIC BLOOD PRESSURE, , Systolic pressure in different age, , Systolic blood pressure (systolic pressure) is defined as, the maximum pressure exerted in the arteries during, systole of heart., Normal systolic pressure: 120 mm Hg (110 mm Hg, to 140 mm Hg)., DIASTOLIC BLOOD PRESSURE, Diastolic blood pressure (diastolic pressure) is defined, as the minimum pressure exerted in the arteries during, diastole of heart., Normal diastolic pressure: 80 mm Hg (60 mm Hg to, 80 mm Hg)., PULSE PRESSURE, Pulse pressure is the difference between the systolic, pressure and diastolic pressure., Normal pulse pressure: 40 mm Hg (120 – 80 = 40)., MEAN ARTERIAL BLOOD PRESSURE, Mean arterial blood pressure is the average pressure, existing in the arteries. It is not the arithmetic mean, of systolic and diastolic pressures. It is the diastolic, pressure plus one third of pulse pressure. To determine, the mean pressure, diastolic pressure is considered, than the systolic pressure. It is because, the diastolic, period of cardiac cycle is longer (0.53 second) than the, systolic period (0.27 second)., Normal mean arterial pressure: 93 mm Hg (80 + 13, = 93)., Formula to calculate mean arterial blood pressure:, Mean arterial blood pressure, = Diastolic pressure + 1/3 of pulse pressure, = 80 +, , 40, 3, , = 93.3 mm Hg, , PHYSIOLOGICAL VARIATIONS, 1. Age, Arterial blood pressure increases as age advances., Newborn, After 1 month, After 6 month, After 1 year, At puberty, At 50 years, At 70 years, At 80 years, , :, :, :, :, :, :, :, :, , 70 mm Hg, 85 mm Hg, 90 mm Hg, 95 mm Hg, 120 mm Hg, 140 mm Hg, 160 mm Hg, 180 mm Hg, , Diastolic pressure in different age, Newborn, After 1 month, After 6 month, After 1 year, At puberty, At 50 years, At 70 years, At 80 years, , :, :, :, :, :, :, :, :, , 40 mm Hg, 45 mm Hg, 50 mm Hg, 55 mm Hg, 80 mm Hg, 85 mm Hg, 90 mm Hg, 95 mm Hg, , 2. Sex, In females, up to the period of menopause, arterial, pressure is 5 mm Hg, less than in males of same age., After menopause, the pressure in females becomes, equal to that in males of same age., 3. Body Built, Pressure is more in obese persons than in lean, persons., 4. Diurnal Variation, In early morning, the pressure is slightly low. It gradually, increases and reaches the maximum at noon. It, becomes low in evening.
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604 Section 8 t Cardiovascular System, 5. After Meals, Arterial blood pressure is increased for few hours after, meals due to increase in cardiac output., 6. During Sleep, Usually, the pressure is reduced up to 15 to 20 mm Hg, during deep sleep. However, it increases slightly during, sleep associated with dreams., 7. Emotional Conditions, During excitement or anxiety, the blood pressure is, increased due to release of adrenaline., 8. After Exercise, After moderate exercise, systolic pressure increases, by 20 to 30 mm Hg above the basal level due to, increase in rate and force of contraction and stroke, volume. Normally, diastolic pressure is not affected, by moderate exercise. It is because, the diastolic, pressure depends upon peripheral resistance, which is, not altered by moderate exercise., After severe muscular exercise, systolic pressure, rises by 40 to 50 mm Hg above the basal level. But,, the diastolic pressure reduces because the peripheral, resistance decreases in severe muscular exercise., More details are given in Chapter 117., PATHOLOGICAL VARIATIONS, Pathological variations of arterial blood pressure are, hypertension and hypotension. Refer applied physiology, of this chapter for details., , DETERMINANTS OF ARTERIAL BLOOD, PRESSURE – FACTORS MAINTAINING, ARTERIAL BLOOD PRESSURE, Some factors are necessary to maintain normal blood, pressure. These factors are called local factors,, mechanical factors or determinants of blood pressure, (Table 103.1)., , 4., 5., 6., 7., 8., 9., , Blood volume, Venous return, Elasticity of blood vessels, Velocity of blood flow, Diameter of blood vessels, Viscosity of blood., , CENTRAL FACTORS, 1. Cardiac Output, Systolic pressure is directly proportional to cardiac, output. Whenever the cardiac output increases, the, systolic pressure is increased and when cardiac output, is less, the systolic pressure is reduced. Cardiac output, increases in muscular exercise, emotional conditions,, etc. So in these conditions, the systolic pressure is, increased. In conditions like myocardial infarction, the, cardiac output decreases, resulting in fall in systolic, pressure., 2. Heart Rate, Moderate changes in heart rate do not affect arterial, blood pressure much. However, marked alteration in the, heart rate affects the blood pressure by altering cardiac, output (Chapter 98)., PERIPHERAL FACTORS, 3. Peripheral Resistance, Peripheral resistance is the important factor, which, maintains diastolic pressure. Diastolic pressure is, directly proportional to peripheral resistance. Peripheral, resistance is the resistance offered to the blood flow, at the periphery. Resistance is offered at arterioles,, which are called the resistant vessels. When peripheral, resistance increases, diastolic pressure is increased, and when peripheral resistance decreases, the diastolic, pressure is decreased., TABLE 103.1: Local factors determining arterial, blood pressure, Arterial blood pressure, , Arterial blood pressure is, directly proportional to, , 1. Cardiac output, 2. Heart rate, 3. Peripheral resistance, 4. Blood volume, 5. Venous return, 6. Velocity of blood flow, 7. Viscosity of blood, , Arterial blood pressure is, inversely proportional to, , 1. Elasticity of blood vessel, 2. Diameter of blood vessel, , Types of Local Factors, Local factors are divided into two types:, A. Central factors, which are pertaining to the heart:, 1. Cardiac output, 2. Heart rate, B. Peripheral factors, which are pertaining to blood, and blood vessels:, 3. Peripheral resistance, , Factors
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Chapter 103 t Arterial Blood Pressure 605, 4. Blood Volume, , 7. Velocity of Blood Flow, , Blood pressure is directly proportional to blood volume., Blood volume maintains the blood pressure through the, venous return and cardiac output. If the blood volume, increases, there is an increase in venous return and, cardiac output, resulting in elevation of blood pressure, (Fig. 103.1)., , Pressure in a blood vessel is directly proportional to, the velocity of blood flow. If the velocity of blood flow, increases, the resistance is increased. So, the pressure, is increased., , 5. Venous Return, Blood pressure is directly proportional to venous return., When venous return increases, there is an increase in, ventricular filling and cardiac output, resulting in eleva, tion of arterial blood pressure., 6. Elasticity of Blood Vessels, Blood pressure is inversely proportional to the elasticity, of blood vessels. Due to elastic property, the blood, vessels are distensible and are able to maintain the, pressure. When the elastic property is lost, the blood, vessels become rigid (arteriosclerosis) and pressure, increases as in old age. Deposition of cholesterol,, fatty acids and calcium ions produce rigidity of blood, vessels and atherosclerosis, leading to increased blood, pressure., , 8. Diameter of Blood Vessels, Arterial blood pressure is inversely proportional to the, diameter of blood vessel. If the diameter decreases, the, peripheral resistance increases, leading to increase in, the pressure., 9. Viscosity of Blood, Arterial blood pressure is directly proportional to the, viscosity of blood. When viscosity of blood increases,, the frictional resistance is increased and this increases, the pressure., , REGULATION OF ARTERIAL, BLOOD PRESSURE, Arterial blood pressure varies even under physiological, conditions. However, immediately it is brought back to, normal level because of the presence of well organized, regulatory mechanisms in the body. Body has four such, regulatory mechanisms to maintain the blood pressure, within normal limits (Fig. 103.2):, A. Nervous mechanism or shortterm regulatory, mechanism, B. Renal mechanism or longterm regulatory, mechanism, C. Hormonal mechanism, D. Local mechanism., , NERVOUS MECHANISM FOR, REGULATION OF BLOOD PRESSURE –, SHORT-TERM REGULATION, , FIGURE 103.1: Effect of blood volume and venous return on, arterial blood pressure, , Nervous regulation is rapid among all the mechanisms, involved in the regulation of arterial blood pressure., When the pressure is altered, nervous system brings the, pressure back to normal within few minutes. Although, nervous mechanism is quick in action, it operates only, for a short period and then it adapts to the new pressure., Hence, it is called shortterm regulation. The nervous, mechanism regulating the arterial blood pressure, operates through the vasomotor system.
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606 Section 8 t Cardiovascular System, , FIGURE 103.2: Regulation of blood pressure. ECF = Extracellular fluid., , Vasomotor System, Vasomotor system includes three components:, 1. Vasomotor center, 2. Vasoconstrictor fibers, 3. Vasodilator fibers., VASOMOTOR CENTER, Vasomotor center is bilaterally situated in the reticular, formation of medulla oblongata and the lower part of, the pons., Vasomotor center consists of three areas:, i. Vasoconstrictor area, ii. Vasodilator area, iii. Sensory area., i. Vasoconstrictor Area, Vasoconstrictor area is also called the pressor, area. It forms the lateral portion of vasomotor center., Vasoconstrictor area sends impulses to blood vessels, through sympathetic vasoconstrictor fibers. So, the, stimulation of this area causes vasoconstriction and rise, in arterial blood pressure. This area is also concerned, with acceleration of heart rate (Chapter 101)., ii. Vasodilator Area, Vasodilator area is otherwise called depressor area., It forms the medial portion of vasomotor center. This, area suppresses the vasoconstrictor area and causes, vasodilatation. It is also concerned with cardioinhibition, (Chapter 101)., , pons. This area receives sensory impulses via glosso, pharyngeal and vagal nerves from the periphery, parti, cularly from the baroreceptors. Sensory area in turn,, controls the vasoconstrictor and vasodilator areas., VASOCONSTRICTOR FIBERS, Vasoconstrictor fibers belong to the sympathetic division, of autonomic nervous system. These fibers cause, vasoconstriction by the release of neurotransmitter, substance, noradrenaline. Noradrenaline acts through, alpha receptors of smooth muscle fibers in blood, vessels., Vasoconstrictor fibers play major role than the, vasodilator fibers in the regulation of blood pressure., Vasomotor Tone, Vasomotor tone is the continuous discharge of impulses, from vasoconstrictor center through the vasoconstrictor, fibers. Vasomotor tone plays an important role in, regulating the pressure by producing a constant partial, state of constriction of the blood vessels. Thus, the arterial, blood pressure is directly proportional to the vasomotor, tone. Vasomotor tone is also called sympathetic, vasoconstrictor tone or sympathetic tone., VASODILATOR FIBERS, Vasodilator fibers are of three types:, i. Parasympathetic vasodilator fibers, ii. Sympathetic vasodilator fibers, iii. Antidromic vasodilator fibers., , iii. Sensory Area, , i. Parasympathetic Vasodilator Fibers, , Sensory area is in the nucleus of tractus solitarius,, which is situated in posterolateral part of medulla and, , Parasympathetic vasodilator fibers cause dilatation of, blood vessels by releasing acetylcholine.
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Chapter 103 t Arterial Blood Pressure 607, ii. Sympathetic Vasodilator Fibers, , Nerve supply, , Some of the sympathetic fibers cause vasodilatation in, certain areas, by secreting acetylcholine. Such fibers, are called sympathetic vasodilator or sympathetic, cholinergic fibers. Sympathetic cholinergic fibers,, which supply the blood vessels of skeletal muscles, are, important in increasing the blood flow to muscles by, vasodilatation, during conditions like exercise., Sympathetic cholinergic vasodilator fibers form, the important part of vasomotor system. Signals for, the vasodilator fibers are generated in cerebral cortex., Signals are relayed through the fibers from cerebral, cortex to lateral gray horn of the spinal cord via, hypothalamus, midbrain and medulla. In the spinal cord,, these impulses activate the preganglionic sympathetic, fibers. These fibers in turn, activate the postganglionic, fibers. Postganglionic fibers cause dilatation of blood, vessels by secreting acetylcholine., , Refer Chapter 101 and Figure 101.3., , iii. Antidromic Vasodilator Fibers, Normally, the impulses produced by a cutaneous recep, tor (like pain receptor) pass through sensory nerve, fibers. But, some of these impulses pass through the, other branches of the axon in the opposite direction and, reach the blood vessels supplied by these branches., These impulses now dilate the blood vessels. It is called, the antidromic or axon reflex and the nerve fibers are, called antidromic vasodilator fibers (see Fig. 113.1,, Chapter 113)., MECHANISM OF ACTION OF, VASOMOTOR CENTER IN THE, REGULATION OF BLOOD PRESSURE, Vasomotor center regulates the arterial blood pressure, by causing vasoconstriction or vasodilatation. However,, its actions depend upon the impulses it receives from, other structures such as baroreceptors, chemoreceptors,, higher centers and respiratory centers. Among these, structures, baroreceptors and chemoreceptors play a, major role in the shortterm regulation of blood pressure., 1. Baroreceptor Mechanism, Baroreceptors are the receptors, which give response, to change in blood pressure. Baroreceptors are also, called pressoreceptors., Situation, Baroreceptors are situated in the carotid sinus and wall, of the aorta (Refer Chapter 101)., , Functions, Role of baroreceptors when blood pressure increases, When arterial blood pressure rises rapidly, baro, receptors are activated and send stimulatory impulses to, nucleus of tractus solitarius through glassopharyngeal, and vagus nerves. Now, the nucleus of tractus solitarius, acts on both vasoconstrictor area and vasodilator areas, of vasomotor center. It inhibits the vasoconstrictor area, and excites the vasodilator area., Inhibition of vasoconstrictor area reduces, vasomotor tone. Reduction in vasomotor tone causes, vasodilatation, resulting in decreased peripheral, resistance. Simultaneous excitation of vasodilator center, increases vagal tone (Chapter 101). This decreases, the rate and force of contraction of heart, leading to, reduction in cardiac output. These two factors, i.e., decreased peripheral resistance and reduced cardiac, output bring the arterial blood pressure back to normal, level (Fig. 103.3)., Role of baroreceptors when blood pressure decreases, The fall in arterial blood pressure or the occlusion of, common carotid arteries decreases the pressure in, carotid sinus. This causes inactivation of baroreceptors., Now, there is no inhibition of vasoconstrictor center or, excitation of vasodilator center. Therefore, the blood, pressure rises., Information regarding blood pressure within the, range of 50 to 200 mm Hg (mean arterial pressure), reaches the vasomotor center through the carotid baro, receptors. Information about the blood pressure range of, 100 to 200 mm Hg goes through aortic baroreceptors., Both carotid and aortic baroreceptors are stimulated, by the rising pressure than the steady pressure and, their response depends upon the rate of increase in the, blood pressure., Since the baroreceptor mechanism acts against, the rise in arterial blood pressure, it is called pressure, buffer mechanism or system and the nerves from, baroreceptors are called the buffer nerves., 2. Chemoreceptor Mechanism, Chemoreceptors are the receptors giving response to, change in chemical constituents of blood. Peripheral, chemoreceptors influence the vasomotor center.
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608 Section 8 t Cardiovascular System, , FIGURE 103.3: Regulation of blood pressure by baroreceptor mechanism, , Situation, , i. Cerebral cortex, , Peripheral chemoreceptors are situated in the carotid, body and aortic body (Chapter 101)., Refer Chapter 101 and Figure 101.3., , Area 13 in cerebral cortex is concerned with emotional, reactions. During emotional conditions, this area sends, impulses to vasomotor center. Vasomotor center is, activated, the vasomotor tone is increased and the, pressure rises., , Function, , ii. Hypothalamus, , Peripheral chemoreceptors are sensitive to lack of, oxygen, excess of carbon dioxide and hydrogen ion, concentration in blood. Whenever blood pressure, decreases, blood flow to chemoreceptors decreases,, resulting in decreased oxygen content and excess of, carbon dioxide and hydrogen ion. These factors excite, the chemoreceptors, which send impulses to stimulate, vasoconstrictor center. Blood pressure rises and blood, flow increases. Chemoreceptors play a major role in, maintaining respiration rather than blood pressure, (Chapter 126)., , Stimulation of posterior and lateral nuclei of hypo, thalamus causes vasoconstriction and increase in, blood pressure. Stimulation of preoptic area causes, vasodilatation and decrease in blood pressure. Impulses, from hypothalamus are mediated via vasomotor center., , Nerve supply, , Sinoaortic mechanism, Mechanism of action of baroreceptors and, chemoreceptors in carotid and aortic region constitute, sinoaortic, mechanism., Nerves, supplying, the, baroreceptors and chemoreceptors are called buffer, nerves because these nerves regulate the heart rate, (Chapter 101), blood pressure and respiration (Chapter, 126)., 3. Higher Centers, Vasomotor center is also controlled by the impulses, from the two higher centers in the brain., , 4. Respiratory Centers, During the beginning of expiration, arterial blood, pressure increases slightly, i.e. by 4 to 6 mm Hg. It, decreases during later part of expiration and during, inspiration because of two factors:, i. Radiation of impulses from respiratory centers, towards vasomotor center at different phases of, respiratory cycle, ii. Pressure changes in thoracic cavity, leading to, alteration of venous return and cardiac output., , RENAL MECHANISM FOR, REGULATION OF BLOOD PRESSURE –, LONG-TERM REGULATION, Kidneys play an important role in the longterm regulation, of arterial blood pressure. When blood pressure alters, slowly in several days/months/years, the nervous
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Chapter 103 t Arterial Blood Pressure 609, mechanism adapts to the altered pressure and looses, the sensitivity for the changes. It cannot regulate the, pressure any more. In such conditions, the renal, mechanism operates efficiently to regulate the blood, pressure. Therefore, it is called longterm regulation., Kidneys regulate arterial blood pressure by two, ways:, 1. By regulation of ECF volume, 2. Through reninangiotensin mechanism., BY REGULATION OF EXTRACELLULAR, FLUID VOLUME, When the blood pressure increases, kidneys excrete, large amounts of water and salt, particularly sodium, by, means of pressure diuresis and pressure natriuresis., Pressure diuresis is the excretion of large quantity of, water in urine because of increased blood pressure., Even a slight increase in blood pressure doubles the, water excretion. Pressure natriuresis is the excretion of, large quantity of sodium in urine., Because of diuresis and natriuresis, there is a, decrease in ECF volume and blood volume, which in, turn brings the arterial blood pressure back to normal, level., When blood pressure decreases, the reabsorption, of water from renal tubules is increased. This in turn,, increases ECF volume, blood volume and cardiac, output, resulting in restoration of blood pressure., , THROUGH RENIN-ANGIOTENSIN MECHANISM, Source of renin secretion, formation of angiotensin, and conditions when renin is secreted are described in, Chapter 50., Actions of Angiotensin II, When blood pressure and ECF volume decrease,, renin secretion from kidneys is increased. It converts, angiotensinogen into angiotensin I. This is converted, into angiotensin II by ACE (angiotensinconverting, enzyme)., Angiotensin II acts in two ways to restore the blood, pressure:, i. It causes constriction of arterioles in the body so, that the peripheral resistance is increased and, blood pressure rises. In addition, angiotensin, II causes constriction of afferent arterioles in, kidneys, so that glomerular filtration reduces., This results in retention of water and salts,, increases ECF volume to normal level. This, in turn increases the blood pressure to normal, level., ii. Simultaneously, angiotensin II stimulates the, adrenal cortex to secrete aldosterone. This, hormone increases reabsorption of sodium from, renal tubules. Sodium reabsorption is followed, by water reabsorption, resulting in increased, , FIGURE 103.4: Regulation of blood pressure by reninangiotensin mechanism. ACE = Angiotensinconverting enzyme.
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610 Section 8 t Cardiovascular System, ECF volume and blood volume. It increases the, blood pressure to normal level (Fig. 103.4)., Actions of Angiotensin III and Angiotensin IV, Like angiotensin II, the angiotensins III and IV also, increase the blood pressure and stimulate adrenal, cortex to secrete aldosterone (Chapter 50)., , HORMONAL MECHANISM FOR, REGULATION OF BLOOD PRESSURE, Many hormones are involved in the regulation of blood, pressure. Hormones, which increase or decrease the, arterial blood pressure are listed in Table 103.2., HORMONES WHICH INCREASE, BLOOD PRESSURE, Hormones, which increase the arterial blood pressure, have different mechanism of action., 1. Adrenaline, Adrenaline is secreted by the adrenal medulla. It is, also released by sympathetic postganglionic nerve, endings. Adrenaline regulates the blood pressure by, acting through heart and blood vessels. It increases, systolic pressure by increasing the force of contraction, of the heart and cardiac output. It decreases diastolic, pressure by reducing the total peripheral resistance., Adrenaline causes constriction of blood vessels, through alpha receptors. It also causes dilatation of, blood vessels through β2receptors in some areas, of the body like skeletal muscle, liver and heart. So,, the total peripheral resistance is reduced leading to, decrease in diastolic pressure (Chapter 71)., 2. Noradrenaline, Noradrenaline is secreted by the adrenal medulla. It, is also released by sympathetic postganglionic nerve, endings. Noradrenaline increases diastolic pressure, due to its general vasoconstrictor effect (Chapter 71). It, has stronger effects on blood vessels than on the heart., It causes constriction of all blood vessels throughout, the body via alpha receptors. So it is called ‘general, vasoconstrictor’. The action of noradrenaline is to, increase the total peripheral resistance and diastolic, pressure., It also increases the systolic pressure slightly, by, increasing the force of contraction of heart., , 3. Thyroxine, Thyroxine secreted form thyroid gland increases, systolic pressure but decreases the diastolic pressure., It increases the systolic pressure by increasing cardiac, output. The cardiac output is increased because of, increase in the blood volume and force of contraction, of the heart (Chapter 67)., Thyroxine has indirect action on diastolic pressure., Large quantities of metabolites are produced during, increased metabolic activity induced by thyroxine. These, metabolites cause vasodilatation, leading to decrease, in peripheral resistance. It causes decrease in diastolic, pressure., Generally, mean arterial pressure is not altered by, the activity of thyroxine. Systolic pressure is increased, and the diastolic pressure is decreased. So, only the, pulse pressure increases., 4. Aldosterone, Aldosterone is secreted from adrenal cortex. It causes, retention of sodium and water and thereby, increases, the ECF fluid volume and blood volume, leading to, increase in blood pressure. Thus, an increase in the, secretion of aldosterone increases the blood pressure, by increasing the blood volume (Chapter 70)., 5. Vasopressin, Vasopressin or ADH, which is secreted by posterior, pituitary has a potent action on the blood vessels,, particularly the arteries. It causes constriction of the, arteries in all parts of the body. Due to the vasoconstriction,, the blood pressure is increased. However, the amount of, this hormone required to cause the vasopressor effect, is very much high than the amount required to cause the, antidiuretic effect (Chapter 66)., 6. Angiotensins, Angiotensin II, III and IV, which are obtained from, angiotensinogen cause constriction of systemic, arterioles and elevate blood pressure (Chapter 50)., 7. Serotonin, Serotonin is otherwise known as 5-hydroxytryptamine., Serotonin is secreted from many sources (refer, Chapter 73 for details). It increases the blood pressure, by vasoconstriction.
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Chapter 103 t Arterial Blood Pressure 611, TABLE 103.2: Hormones involved in regulation, of arterial blood pressure, Hormones which increase, arterial blood pressure, , Hormones which decrease, arterial blood pressure, , 1. Adrenaline*, 2. Noradrenaline, 3. Thyroxine*, 4. Aldosterone, 5. Vasopressin, 6. Angiotensin, 7. Serotonin, , 1. Vasoactive intestinal, polypeptide (VIP), 2. Bradykinin, 3. Prostaglandin, 4. Histamine, 5. Acetylcholine, 6. Atrial natriuretic peptide, 7. Brain natriuretic peptide, 8. Ctype natriuretic peptide, , *Adrenaline and thyroxine increase systolic pressure but, decrease diastolic pressure., , HORMONES WHICH DECREASE, BLOOD PRESSURE, Following hormones decrease the arterial blood pressure, by causing vasodilatation:, 1. Vasoactive Intestinal Polypeptide, Vasoactive intestinal polypeptide (VIP) is secreted in, the stomach and small intestine. A small amount of, this hormone is also secreted in large intestine. VIP is, a vasodilator and causes dilatation of peripheral blood, vessels and decrease in blood pressure., 2. Bradykinin, Bradykinin is produced in blood during the conditions, like inflammation. During such conditions, the enzyme, in the blood called kallikrein is activated. It acts on, α2globulin to form kallidin, which is converted into, bradykinin (Chapter 73)., Bradykinin is a vasodilator substance and causes, reduction in blood pressure., 3. Prostaglandins, Prostaglandin PGE2 is a vasodilator substance. It is, secreted from almost all tissues of the body (Chapter, 73). It decreases blood pressure., 4. Histamine, Histamine is secreted in nerve endings of hypothalamus,, limbic cortex and other parts of cerebral cortex. Histamine, is also released from tissues during allergic conditions,, inflammation or damage (Chapter 73)., Histamine causes vasodilatation and decreases the, blood pressure., , 5. Acetylcholine, Acetylcholine is the cholinergic neurotransmitter released, from many sources (Chapter 73). Acetylcholine causes, vasodilatation and decreases the blood pressure., 6. Atrial Natriuretic Peptide, Atrial natriuretic peptide (ANP) is a hormone secreted, by the atrial musculature of heart. It causes dilatation, of blood vessels and decreases the blood pressure, (Chapter 72)., 7. Brain Natriuretic Peptide, Brain natriuretic peptide (BNP) is a hormone secreted, by the atrial musculature of heart. Like ANP, this, hormone also causes dilatation of blood vessels and, decreases the blood pressure (Chapter 72)., 8. C-type Natriuretic Peptide, Ctype natriuretic peptide (CNP) is secreted by several, tissues including myocardium and vascular endothelium, (Chapter 71). CNP decreases blood pressure by, vasodilatation., , LOCAL MECHANISM FOR REGULATION, OF BLOOD PRESSURE, In addition to nervous, renal and hormonal mechanisms,, some local substances also regulate the blood pressure., The local substances regulate the blood pressure by, vasoconstriction or vasodilatation., LOCAL VASOCONSTRICTORS, Local vasoconstrictor substances are derived from, vascular endothelium. These substances are called, endothelium-derived constricting factors (EDCF)., Common EDCF are endothelins (ET), which are peptides, with 21 amino acids. Three types of endothelins ET1,, ET2 and ET3 are identified so far., Endothelins are produced by stretching of blood, vessels. These peptides act by activating phospholipase,, which in turn activates prostacyclin and thromboxane, A2. These two substances cause constriction of blood, vessels and increase the blood pressure., LOCAL VASODILATORS, Local vasodilators are of two types:, 1. Vasodilators of metabolic origin, 2. Vasodilators of endothelial origin.
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612 Section 8 t Cardiovascular System, Vasodilators of Metabolic Origin, Vasodilators of metabolic origin are carbon dioxide,, lactate, hydrogen ions and adenosine (Table 103.3)., Vasodilators of Endothelial Origin, Nitric oxide (NO) is an endotheliumderived relaxing, factor (EDRF). It is synthesized from arginine. Nitric oxide, synthesis is stimulated by acetylcholine, bradykinin,, VIP, substance P and platelet breakdown products. As, nitric oxide is a vasodilator, deficiency of this leads to, constant vasoconstriction and hypertension., Other functions of nitric oxide are penile erection with, vasodilatation and engorgement of corpora cavernosa,, activation of macrophages in brain, destruction of, cancer cells and relaxation of smooth muscles of, gastrointestinal tract., i. NO3 (nitrate), ii. NO+ (nitrosonium cation), iii. NO– (nitroxyl anion)., , Apparatus, , MEASUREMENT OF ARTERIAL, BLOOD PRESSURE, Blood pressure was first measured in horse in 1733, by, Stephen Hales, with a long tube of about 9 feet length., Later, Poiseuille reduced the length of the tube to one, foot and used mercury to balance the column of blood., In 1847, Ludwig placed a float on the top of mercury, column and made continuous recording possible., Introduction of rubber tubing, anesthesia and manometer, enabled the accurate measurement of blood pressure., Blood pressure is measured by two methods:, A. Direct method, B. Indirect method., DIRECT METHOD, Direct method to measure arterial blood pressure, is employed only in animals. Animal is given suitable, TABLE 103.3: Local substances involved in the, regulation of arterial blood pressure, Local vasodilators, , EDCF:, 1. ET1, 2. ET2, 3. ET3, , Metabolic, products, 1., 2., 3., 4., , Carbon dioxide, Lactate, Hydrogen, Adenosine, , INDIRECT METHOD, Indirect method is used to measure arterial blood, pressure in man as well as in animals., , Types of nitric oxide, , Local, vasoconstrictors, (Endothelins), , anesthesia, then the neck is opened and a tracheal, cannula is inserted into the trachea. This tracheal, cannula is connected to a respiratory pump, so that the, respiration in the animal is controlled artificially to avoid, any disturbance during the experimental procedure. A, venous cannula is inserted through the femoral vein. It, is used to infuse saline to compensate blood loss during, experimental procedure., Carotid artery is cannulated and connected to a, mercury manometer. By using a kymograph, the blood, pressure can be recorded continuously in the form of, graph. The cannula inserted into carotid artery can also, be connected to an electronic pressure transducer,, which in turn is connected to a recording device like, polygraph to obtain the recordings., , Endothelins (ET), EDRF:, 1. Nitric oxide, , Apparatus used to measure blood pressure in human, beings is called sphygmomanometer. Along with, sphygmomanometer, stethoscope is also necessary to, measure blood pressure., Principle, When an external pressure is applied over the artery,, the blood flow through it is obstructed. And the pressure, required to cause occlusion of blood flow indicates the, pressure inside the vessel., Procedure, Brachial artery is usually chosen because of, convenience. The arm cuff of sphygmomanometer is, tied around upper arm, above the cubital fossa. Cuff, should not be too tight or too loose. It is connected, to sphygmomanometer. Now, blood pressure can be, measured by three methods., 1. Palpatory method, 2. Auscultatory method, 3. Oscillatory method., 1. Palpatory method, First, the radial pulse is felt. While feeling the pulse,, pressure is increased in the cuff by inflating air into it,, with the help of a hand pump. While doing this, mercury, column in the sphygmomanometer shows the pressure, in the cuff., When pressure is increased in the arm cuff, brachial, artery is compressed and blood flow is obstructed. So,
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Chapter 103 t Arterial Blood Pressure 613, radial pulse disappears. When radial pulse disappears,, the pressure is further increased by about 20 mm Hg., Then, the pressure in the cuff is slowly reduced by, releasing the valve of the hand pump, i.e. the cuff is, deflated slowly. This is done by feeling the pulse and, simultaneously watching the mercury column in the, apparatus. Pressure is noted when the pulse reappears., This pressure indicates the systolic pressure., Disadvantage of palpatory method is that the, diastolic pressure cannot be measured., 2. Auscultatory method, Auscultatory method is the most accurate method to, determine arterial blood pressure. After determining, the systolic pressure in palpatory method, the pressure, in the cuff is raised by about 20 mm Hg above that, level, so that the brachial artery is occluded due to, compression. Now, the chest piece of the stethoscope, is placed over the antecubital fossa and the arm cuff, is slowly deflated. While doing so, series of sounds, are heard through the stethoscope. These sounds, are known as Korotkoff sounds, named after the, discoverer Korotkoff (1905). While reducing the, pressure, Korotkoff sounds have five phases:, First phase – appearance of tapping sound, While decreasing the pressure from arm cuff, the, occlusion of the artery is relieved and when blood starts, flowing through the artery, first sound appears suddenly., In a normal person, it appears, when the pressure is, reduced to 120 mm Hg. It is a clear tapping sound., Appearance of tapping sound indicates systolic, pressure. When the pressure is reduced further by 10, mm Hg from the initial level, this sound slowly becomes, louder., Second phase – appearance of murmuring sound, Following the clear taping sound, a murmuring sound, is heard when the pressure is reduced further by about, 15 mm Hg., Third phase – appearance of gong sound, After the murmuring sound, a very clear and louder, sound is heard. It is of gong type. It is heard while, reducing the pressure by another 15 mm Hg., Fourth phase – appearance of muffled sound, Next to the gong type sound, a mild and muffled sound, is heard when the pressure is decreased further by, 5 mm Hg., , Thus, in auscultatory method, the appearance of, clear tapping sound during first phase indicates the, systolic pressure and disappearance of the muffling, sound in fifth phase shows diastolic pressure., 3. Oscillatory method, When pressure in the arm cuff is increased above the, level of systolic pressure, the artery is occluded due, to compression. At this stage, the mercury column in, the manometer remains static. When the pressure is, gradually reduced, some oscillations occur at the top of, the mercury column. While deflating the cuff further, the, amplitude and duration of oscillations increase suddenly., It denotes systolic pressure. When the cuff pressure is, reduced further, the amplitude and duration of oscillations, is reduced. It reflects the diastolic pressure., Because of its inaccuracy, this method is not followed, in routine clinical practice. By connecting the manometer, to an appropriate recording device, the oscillations of, mercury column can be recorded graphically., Automatic Blood Pressure Instrument, Nowadays automatic blood pressure instrument is, widely used. The instrument has a microprocessordriven air pump, which automatically inflates the arm, cuff at a fixed pressure value. Then, it records the, pressure oscillation pattern during a stepwise deflation., The principle of measuring pressure depends up on, the nonlinear properties of brachial arterial wall, which, induce nonconstant oscillations of the cuff pressure, during deflation. The sensors in the instrument detect, the oscillometric waves and determine the systolic, pressure, diastolic pressure, pulse pressure and mean, arterial pressure. The instrument determines the pulse, rate also., Automatic instrument does not need expert, personnel to measure the blood pressure since it has, the selfmeasuring facilities. However, the accuracy of, oscillometric method is still controversial., Microprocessor controlled blood pressure monitors, that are fixed around wrist or finger are also available., , APPLIED PHYSIOLOGY, Pathological variations of arterial blood pressure:, A. Hypertension, B. Hypotension., HYPERTENSION, , Fifth phase – disappearance of muffled sound, , Definition, , Muffling sound disappears. Disappearance of this sound, indicates diastolic pressure., , Hypertension is defined as the persistent high blood, pressure. Clinically, when the systolic pressure remains
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614 Section 8 t Cardiovascular System, elevated above 150 mm Hg and diastolic pressure, remains elevated above 90 mm Hg, it is considered, as hypertension. If there is increase only in systolic, pressure, it is called systolic hypertension., Types of Hypertension, Hypertension is divided into two types:, 1. Primary hypertension or essential hypertension, 2. Secondary hypertension., 1. Primary Hypertension or, Essential Hypertension, Primary hypertension is the elevated blood pressure, in the absence of any underlying disease. It is also, called essential hypertension. Arterial blood pressure is, increased because of increased peripheral resistance,, which occurs due to some unknown cause., Primary hypertension is of two types:, i. Benign hypertension, ii. Malignant hypertension., i. Benign hypertension, Benign hypertension is the high blood pressure that does, not cause any problem. It is defined as the essential, hypertension that runs a relatively long and symptomless, course. In early stages of this condition, there is moderate, increase in blood pressure, with systolic pressure of, 200 mm Hg and the diastolic pressure of about 100 mm, Hg. However, in resting conditions and sleep, the blood, pressure returns to normal level. Later, there is a further, increase in blood pressure and it does not come back to, normal level in resting conditions. Persistent increase in, pressure over the years causes development of vascular,, cardiac or renal diseases., ii. Malignant hypertension, Malignant hypertension is a severe form of hypertension, with a rapid course leading to progressive cardiac and, renal diseases. It is also called accelerated hypertension., In this case, the blood pressure is elevated to a great, extent. Systolic pressure rises to about 250 mm Hg, and diastolic pressure rises to 150 mm Hg. It is always, developed due to the combined effects of primary and, secondary hypertension. Malignant hypertension cause, severe damage of tunica intima of small blood vessels, and organs like eye (retina), heart, brain and kidneys. It is, a fatal disease, since it causes death within few years., 2. Secondary Hypertension, Secondary hypertension is the high blood pressure due, to some underlying disorders. The different forms of, secondary hypertension are:, , i. Cardiovascular hypertension, Cardiovascular hypertension is produced due to the, cardiovascular disorders such as:, a. Atherosclerosis: Hardening of blood vessels due to, fat deposition, b. Coarctation of aorta: Narrowing of aorta., ii. Endocrine hypertension, Endocrine hypertension is developed because of hyper, activity of some endocrine glands:, a. Pheochromocytoma: Tumor in adrenal medulla,, resulting in excess secretion of catecholamines, b. Hyperaldosteronism: Excess secretion of aldos, terone from adrenal cortex, c. Cushing syndrome: Excess secretion of gluco, corticoids from adrenal cortex., iii. Renal hypertension, Renal diseases causing hypertension:, a. Stenosis of renal arteries, b. Tumor of juxtaglomerular cells, leading to excess, production of angiotensin II, c. Glomerulonephritis., iv. Neurogenic hypertension, Nervous disorders producing hypertension:, a. Increased intracranial pressure, b. Lesion in tractus solitarius, c. Sectioning of nerve fibers from carotid sinus., v. Hypertension during pregnancy, Some pregnant women develop hypertension because, of toxemia of pregnancy. Arterial blood pressure, is elevated by the low glomerular filtration rate and, retention of sodium and water. It may be because of, some autoimmune processes during pregnancy or, release of some vasoconstrictor agents from placenta, or due to the excessive secretion of hormones causing, rise in blood pressure. Hypertension is associated with, convulsions in eclampsia (Chapter 84)., Experimental Hypertension, Hypertension can be produced in experimental animals, by various methods. These methods correlate with the, causes of hypertension in human beings., Experimental hypertension is produced by the, following methods:, 1. Clamping the renal artery, 2. Denervation of baroreceptors in carotid sinus and, aortic arch
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Chapter 103 t Arterial Blood Pressure 615, 3. Injections of corticosteroids, 4. Infusion of salt with aldosterone., , the contractility of myocardium. It causes decrease in, cardiac output and fall in blood pressure., , Goldblatt hypertension, , 4. Vasodilators, , Goldblatt hypertension is one of the experimental, hypertension produced in dogs by Goldblatt and it is, named after him. He removed one kidney of the dog and, clamped the artery of other kidney. It produced slow and, steady increase in arterial pressure. The elevation of, blood pressure was due to excessive secretion of renin, from intact kidney, leading to the formation of a large, quantity of angiotensin II. It is known as ‘one kidney, Goldblatt hypertension’. Hypertension is also developed, when the artery of one kidney is clamped without doing, anything with the kidney of the other side. It is called, ‘two kidney Goldblatt hypertension’. It is due to the, reninangiotensin mechanism and retention of salts., , Vasodilator agents reduce blood pressure by vaso, dilatation., , Manifestations of Hypertension, Severe manifestations of primary hypertension:, 1. Renal failure, 2. Left ventricular failure, 3. Myocardial infarction, 4. Cerebral hemorrhage, 5. Retinal hemorrhage., , 5. Diuretics, Diuretics cause diuresis and reduce the ECF volume, and blood volume. So, blood pressure is decreased., 6. Inhibitors of angiotensin-converting enzyme, (ACE inhibitors), ACE inhibitors reduce the blood pressure by blocking, the formation of angiotensin., 7. Depressors of vasomotor center, Depressor drugs act on vasomotor center and reduce, the vasomotor tone. So, vasoconstriction is prevented., 8. Angiotensin II receptor blockers, Angiotensin II receptor blockers or antagonists are, the antihypertensive drugs that decrease the blood, pressure by blocking the effect of angiotensin II, (vasoconstriction and secretion of aldosterone)., HYPOTENSION, , Treatment of Hypertension, , Definition, , Secondary hypertension is cured by treating the disease, causing hypertension. Primary hypertension can be, controlled but cannot be cured., Following are the antihypertensive drugs to control, primary hypertension:, , Hypotension is the low blood pressure. When the, systolic pressure is less than 90 mm Hg, it is considered, as hypotension., , 1. Beta adrenoceptor blockers, Beta adrenoceptor blockers or beta antagonists, (adrenergic beta blockers or beta blockers) block, , the effect of sympathetic nerves on heart and blood, vessels by binding with beta adrenoceptors, so that, there is reduction in cardiac output and inhibition of, vasoconstriction, leading to fall in blood pressure., 2. Alpha adrenoceptor blockers, , Alpha adrenoceptor blockers or alpha antagonists, (adrenergic alpha blockers or alpha blockers) block the, effect of sympathetic nerves on blood vessels by binding, with alpha adrenoceptors, leading to vasodilatation and, fall in blood pressure., 3. Calcium channel blockers, Calcium channel blockers are drugs, which block the, calcium channels in myocardium and thereby, reduce, , Types, 1. Primary hypotension, 2. Secondary hypotension., 1. Primary hypotension, Primary hypotension is the low blood pressure that, develops in the absence of any underlying disease and, develops due to some unknown cause. It is also called, essential hypotension. Frequent fatigue and weakness, are the common symptoms of this condition. However,, the persons with primary hypotension are not easily, susceptible to heart or renal disorders., 2. Secondary hypotension, Secondary hypotension is the hypotension that occurs, due to some underlying diseases. Diseases, which, cause hypotension are:, i. Myocardial infarction, ii. Hypoactivity of pituitary gland, iii. Hypoactivity of adrenal glands
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616 Section 8 t Cardiovascular System, iv. Tuberculosis, v. Nervous disorders., Orthostatic hypotension, Orthostatic hypotension is the sudden fall in blood, pressure while standing for some time. It is due to, , the effect of gravity. It develops in persons affected, by myasthenia gravis or some nervous disorders like, tabes dorsalis, syringomyelia and diabetic neuro, pathy. Common symptom of this condition is orthostatic syncope. Syncope is described in detail in, Chapter 116.
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Chapter, , Venous Pressure, , 104, , DEFINITION AND NORMAL VALUES, , , , VENOUS PRESSURE IN EXTREMITIES OF THE BODY, VENOUS PRESSURE IN CENTRAL AND PERIPHERAL VEINS, , VARIATIONS OF VENOUS PRESSURE, , , , PHYSIOLOGICAL VARIATIONS, PATHOLOGICAL VARIATIONS, , MEASUREMENT, , , , DIRECT METHOD, INDIRECT METHOD, , FACTORS REGULATING VENOUS PRESSURE, , , , , , , , LEFT VENTRICULAR CONTRACTION OR VIS A TERGO, RIGHT ATRIAL PRESSURE OR VIS A FRONTE, RESISTANCE OR VIS A LATRE, VOLUME OF VENOUS BLOOD, PERIPHERAL RESISTANCE, GRAVITY AND POSTURE, , EFFECT OF RESPIRATION ON VENOUS PRESSURE, , , , VALSALVA MANEUVER, MÜELLER MANEUVER, , DEFINITION AND NORMAL VALUES, Venous pressure is the pressure exerted by the, contained blood in the veins. The pressure in vena cava, and right atrium is called central venous pressure. The, pressure in peripheral veins is called peripheral venous, pressure., , Pressure is not same in all the veins. It varies in, different veins in the extremities of the body and also, varies from central veins to peripheral veins., VENOUS PRESSURE IN EXTREMITIES, OF THE BODY, Venous pressure is less in the parts of the body above, the level of the heart and it is more in parts below the, level of the heart. Pressure in:, , Jugular vein: 5.1 mm Hg (6.9 cm H2O), Dorsal venous arch of foot: 13.2 mm Hg (17.9 cm, H2O)., (1 mm Hg pressure = 1.359 cm H2O pressure), VENOUS PRESSURE IN CENTRAL, AND PERIPHERAL VEINS, Pressure is greater in peripheral veins than in central, veins. Pressure in:, Antecubital vein: 7.1 mm Hg (9.6 cm H2O), Superior vena cava: 4.6 mm Hg (6.2 cm H2O)., , VARIATIONS OF VENOUS PRESSURE, Venous pressure is altered both in physiological and, pathological conditions.
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618 Section 8 t Cardiovascular System, PHYSIOLOGICAL VARIATIONS, Venous pressure increases in:, 1. Changing from standing to supine position, 2. Tilting the body, 3. Forced expiration (Valsalva maneuver), 4. Contraction of abdominal and limb muscles, 5. Effect of gravity during prolonged travelling or, standing, 6. Excitement., PATHOLOGICAL VARIATIONS, Venous pressure increases in:, 1. Low cardiac output, 2. Congestive heart failure, 3. Venous obstruction, 4. Failure of valves in veins, 5. Paralysis of muscles, 6. Immobilization of parts of body, 7. Renal failure., Venous pressure decreases in:, 1. Severe hemorrhage, 2. Surgical shock., , MEASUREMENT OF VENOUS PRESSURE, DIRECT METHOD, Central venous pressure is measured by a catheter, introduced through median cubital vein of forearm., Position of tip of the catheter is checked by fluoroscopy., Other end of catheter is connected to a manometer,, which measures the pressure. Peripheral venous, pressure is measured by using a needle connected to, a manometer., INDIRECT METHOD, Measurement of venous pressure is done by using, an apparatus designed by Ranger. By this apparatus,, collapse of the vein is noticed by the reflection of, light through a transparent device. Pressure required, to cause the collapse of peripheral vein denotes the, pressure in the particular vein., , FACTORS REGULATING, VENOUS PRESSURE, 1. LEFT VENTRICULAR CONTRACTION, OR VIS A TERGO, Left ventricular contraction is also called vis a tergo, or force from behind. It forces the blood through the, arteries, arterioles, capillaries and veins to the right, , atrium. Venous pressure is directly proportional to left, ventricular pressure. By the time blood passes through, capillaries and reaches the venules, the pressure, becomes less than 8 mm Hg and when it reaches right, atrium, the pressure may be less than 1 mm Hg., 2. RIGHT ATRIAL PRESSURE OR, VIS A FRONTE, Right atrial pressure is also called vis a fronte or force, from front. It determines the venous return. It is also, called central venous pressure, which in turn regulates, the peripheral venous pressure. Normal right atrial, pressure is 0 mm Hg., 3. RESISTANCE OR VIS A LATRE, Resistance offered to blood flow through the veins is also, called vis a latre or force from side. Venous pressure is, directly proportional to the resistance, which is due to, venous tone and extravascular factors. Because of the, thin-walled nature, veins and venules are compressed, by the extravascular factors such as:, i. Compression of arm vein while passing over, first rib, ii. Compression of neck veins in erect posture due, to fall in pressure and by atmospheric pressure, iii. Compression of abdominal veins by increased, intra-abdominal pressure, iv. Compression of veins while passing in between, the muscles., 4. VOLUME OF VENOUS BLOOD, Venous pressure is directly proportional to the volume, of blood in the venous system., 5. PERIPHERAL RESISTANCE, Venous pressure is inversely proportional to peripheral, resistance. When peripheral resistance is more,, arterioles constrict and the veins are filled with less, blood. Hence, the pressure decreases. When peripheral, resistance is less, the veins are filled with more blood, and venous pressure increases., 6. GRAVITY AND POSTURE, Pressure is more in the veins below the level of heart and, the pressure is less in veins above the level of heart., Weight of the column of blood in veins influences, the venous pressure. During prolonged standing, the, pressure in lower extremities is more (90 cm H2O). It is
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Chapter 104 t Venous Pressure 619, TABLE 104.1: Valsalva maneuver Vs Müeller maneuver, Features, , Valsalva maneuver, , Müeller maneuver, , 1. Intrathoracic pressure, , Increases up to +50 mm Hg, , Decreases up to –70 mm Hg, , 2. Central vein in thorax, , Compressed, , Dilated and blood rushes, , 3. Venous return to right atrium, , Decreases, , Increases, , 4. Peripheral venous pressure, , Increases to 30 cm H2O, , Decreases to 3 cm H2O, , 5. Central venous pressure, , Decreases, , Increases, , because of pooling of blood in the legs due to gravity. It, increases the weight of the column of blood, leading to, increase in pressure. During the movement, the venous, pressure in foot decreases., In head region, the venous pressure is –10 cm, H2O because of the hydrostatic suction below the skull., So, there is always a negative venous pressure in the, head., , Uses of Valsalva Maneuver, , EFFECT OF RESPIRATION ON, VENOUS PRESSURE, , The subject is asked to blow against sphygmomanometer, in which the pressure is maintained at 40 mm Hg, for 30 seconds. Then the changes in heart rate, blood, pressure or murmurs are observed to evaluate the, cardiovascular disorders., , During normal quiet breathing, the central venous, pressure is altered in accordance with intrathoracic, pressure. Thus, during inspiration, the central venous, pressure decreases because of decreased intrathoracic, pressure. During expiration, it increases because of, increased intrathoracic pressure., The effect of respiration on venous pressure is, demonstrated by some procedures which exaggerate, these effects on venous pressure. Such procedures, are Valsalva maneuver and Mueller maneuver., VALSALVA MANEUVER OR, VALSALVA EXPERIMENT, Valsalva maneuver is the forced expiratory effort with, closed glottis. It is performed by attempting to exhale, forcibly, while keeping the mouth and nose closed., Effects of Valsalva Maneuver, During this maneuver, the intrathoracic pressure, becomes positive and increases greatly. It may reach, +50 mm Hg. High intrathoracic pressure produces the, following effects (Table 104.1):, 1. Compression of central vein in thorax, 2. Decrease in venous return to right atrium, 3. Increase in peripheral venous pressure to about 30, cm H2O, due to accumulation of blood in peripheral, veins such as veins of neck, face and limbs, 4. Decrease in central venous pressure., , 1. Valsalva maneuver is used as a diagnostic tool, to evaluate the cardiovascular disorders. Best, example is the 30 minutes endurance test., 2. Valsalva maneuver is practiced to relieve chest, pain, 3. It is used to correct the abnormal heart rhythms., 30 seconds endurance test, , MÜELLER MANEUVER OR, MÜELLER EXPERIMENT, Müeller maneuver or experiment is the forced inspiratory, effort with closed glottis. It is performed by attempting, to inhale forcibly, while keeping the mouth and nose, closed. It is also called reverse Valsalva maneuver., Effects of Müeller Maneuver, During this maneuver, the intrathoracic pressure, decreases greatly (becomes more negative). It is about, –70 mm Hg. This pressure produces the following, effects (Table 104.1):, 1. Dilatation of right atrium and central vein because of, increase in negative intrathoracic pressure, 2. Rapid emptying of blood from peripheral veins into, the central veins and increase in venous return to, right atrium, 3. Decrease in peripheral venous pressure to less than, 3 to 4 cm H2O, 4. Increase in central venous pressure., Uses of Müeller Maneuver, Müeller maneuver is used to evaluate:, 1. Upper respiratory tract problems, 2. Sleep apnea syndrome.
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Capillary Pressure, , , , , , , Chapter, , 105, , INTRODUCTION, REGIONAL VARIATIONS, MEASUREMENT, REGULATION, CAPILLARY ONCOTIC PRESSURE, , INTRODUCTION, , Capillary Pressure in Lungs, , Definition, , In lungs, the pulmonary capillary pressure is low and it, is about 7 mm Hg. It favors exchange of gases between, blood and alveoli., , Capillary pressure is the pressure exerted by the, blood contained in capillary. It is also called capillary, hydrostatic pressure., , MEASUREMENT, , Significance, , Direct Method, , Capillary pressure is responsible for the exchange of, various substances between blood and interstitial fluid, through capillary wall., , Capillary pressure was first measured by EM Landis,, when he was a medical student. Minute vessels in the web, of foot in a frog were cannulated by using micropipette,, with a diameter of 5 µ at the tip with the aid of microscope., The cannula was connected to a manometer., This method was later followed to measure capillary, pressure in other organs., , Normal Values, Generally, the pressure in the arterial end of the capillary, is about 30 to 32 mm Hg and in venous end it is 15 mm, Hg. However, capillary pressure varies depending upon, the function of the organ or region of the body., , REGIONAL VARIATIONS, Regional variation in capillary pressure is in relation to, the physiological activities of the particular region. So,, it has some functional significance. Capillary pressure, remarkably varies in kidneys and lungs., Capillary Pressure in Kidneys, In kidneys, the glomerular capillary pressure is high., It is about 60 mm Hg. This high capillary pressure is, responsible for glomerular filtration., , Indirect Method, Indirect method is based upon the principle of exerting, an external pressure necessary to obstruct the flow of, blood in capillaries. The capillaries are observed under, microscope., , REGULATION, Arterioles play an important role in regulating the, capillary pressure and the pressure in capillaries is, considered as a function of arteriolar resistance., When the arterioles constrict, resistance increases, in arterioles, which raises the arterial blood pressure. At
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Chapter 105 t Capillary Pressure 621, the same time, the volume of blood flowing into capillaries, decreases, leading to fall in capillary pressure., On the other hand, during dilatation of arterioles,, the resistance decreases and arterial blood pressure, decreases. But the capillary pressure increases because, of increase in volume of blood flowing into capillaries, (Fig. 105.1)., , CAPILLARY ONCOTIC PRESSURE, , FIGURE 105.1: Regulation of capillary pressure, , Capillary membrane is permeable to all substances, except plasma proteins. So, the plasma proteins stay, within the capillaries and exert some pressure which is, called oncotic pressure or colloidal osmotic pressure., Normal oncotic pressure is about 25 mm Hg. Among, the plasma proteins, albumin exerts 70% of oncotic, pressure., Oncotic pressure plays an important role in filtration, across capillary membrane, particularly in renal glome, rular capillaries.
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Chapter, , Arterial Pulse, , 106, , INTRODUCTION, TRANSMISSION OF PULSE, , , , VELOCITY OF TRANSMISSION OF PULSE, DELAY IN TRANSMISSION OF PULSE, , METHODS OF RECORDING ARTERIAL PULSE, , , , , BY MANOMETER, BY DUDGEON SPHYGMOGRAPH, BY ELECTRONIC PULSE TRANSDUCER, , INTERPRETATION OF ARTERIAL PULSE TRACING, PULSE POINTS, EXAMINATION OF RADIAL PULSE, , , , , , , , RATE, RHYTHM, CHARACTER, VOLUME, CONDITION OF THE BLOOD VESSEL WALL, DELAYED PULSE, , APPLIED PHYSIOLOGY – ABNORMAL PULSE, , , , , , , , , , PULSUS DEFICIT, PULSUS ALTERNANS, ANACROTIC PULSE, THREADY PULSE OR WEAK PULSE, PULSUS PARADOXUS, WATER HAMMER PULSE, ABNORMAL PULSE IN PATENT DUCTUS ARTERIOSUS, ABNORMAL PULSE IN AORTIC REGURGITATION, , INTRODUCTION, Arterial pulse is defined as the pressure changes, transmitted in the form of waves through arterial wall, and blood column from heart to periphery., When heart contracts, the blood is ejected into aorta, with great force. It causes distension of this blood vessel, and a rise in pressure. A pressure wave is produced, on the elastic wall of the aorta. It travels rapidly from, the heart and can be felt after a brief interval, at any, superficial peripheral artery like radial artery at wrist., , Pulse rate is the accurate measure of heart rate,, except in conditions like pulses deficit (see below)., , TRANSMISSION OF PULSE, Central arterial pulse is transmitted to the peripheral, arteries as peripheral arterial pulse. Formation and, transmission of pulse wave depends upon the elasticity, of blood vessels. Thus, when the walls of the arteries, are more distensible, the pressure rise is less and so, the transmission of pulse is less. When the arterial wall
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Chapter 106 t Arterial Pulse 623, loses its elastic property and becomes rigid as in old, age, the pressure rise is more and the transmission of, pulse is also more., Pulse is not transmitted to capillaries because, capillaries are devoid of elastic tissues., , INTERPRETATION OF ARTERIAL, PULSE TRACING, Pulse recorded in radial artery or femoral artery is the, typical peripheral pulse (Fig. 106.1). Peripheral pulse, tracing has three main features:, , VELOCITY OF TRANSMISSION OF PULSE, Average velocity at which the pulse wave is transmitted, varies between 7 and 9 meter/second. Pulse travels, faster than the blood. Maximum velocity of blood flow in, the body (in larger arteries) is only 50 cm/second., , 1. Anacrotic Limb, , DELAY IN TRANSMISSION OF PULSE, , 2. Catacrotic Limb, , At the arteries, pulse is felt after a short interval from the, beginning of ventricular systole. This delay is very small, and it can be measured only by accurate recording. The, delay is directly proportional to the distance from heart., Delay of pulse at:, 1. Common carotid artery: 0.01 to 0.02 second, 2. Radial artery: About 0.08 second., , Catacrotic limb is the descending limb or downstroke. It, is due to the fall in pressure during diastole., , METHODS OF RECORDING, ARTERIAL PULSE, , Anacrotic limb or primary wave is the ascending limb, or upstroke. It is due to the rise in pressure during, systole., , 3. Catacrotic Notch, In the upper part of the catacrotic limb of pulse tracing,, a small notch appears. It is known as catacrotic notch, or incisura. This notch is produced by the backflow, of blood during the closure of semilunar valves at the, beginning of diastolic period, which produces slight, increase in the pressure., , BY MANOMETER, In animals, pulse is recorded by inserting a cannula, into the dissected artery. This cannula is connected to a, manometer or any recording device., BY DUDGEON SPHYGMOGRAPH, Dudgeon sphygmograph is tied to the wrist in such a way, that, a small plate rests on the skin over radial artery., Movements of arterial wall are magnified by a series of, levers and are recorded on a moving strip of smoked, paper. This instrument is outdated and it is replaced by, electronic pulse transducers., , 4. Precatacrotic and Postcatacrotic Waves, The wave appearing before the catacrotic notch is, called precatacrotic wave. The wave appearing after, the notch is called postcatacrotic wave., , PULSE POINTS, Usually, pulse is palpated on the radial artery because it, is easily approachable and placed superficially. However,, arterial pulse can be felt in different areas on the body., These areas are called pulse points. Pulse points and, the area of palpation are given in Table 106.1., , BY ELECTRONIC PULSE TRANSDUCER, Pulse transducer is placed over the finger and tied., This device throws light on the blood vessel through, skin. Sensor of the transducer detects the light rays, reflected from the flowing blood. Alteration in frequency, of the reflected light rays is amplified and recorded by, connecting the transducer to a recording device like, polygraph. The record shows finger pulse volume, which, represents the arterial pulse tracing., , FIGURE 106.1: Radial pulse tracing
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624 Section 8 t Cardiovascular System, TABLE 106.1: Pulse points, Pulse point, , Area of palpation, , 1. Temporal pulse, , Over the temple, in front of ear on superficial temporal artery, , 2. Facial pulse, , On facial artery at the angle of jaw, , 3. Carotid pulse, , In the neck along anterior border of sternocleidomastoid muscle on common carotid artery, , 4. Axillary pulse, , In axilla on axillary artery, , 5. Brachial pulse, , In cubital fossa along medial border of biceps muscle on brachial artery, , 6. Radial pulse, , Over the thumbside of wrist between tendons of brachioradialis and flexor carpi radialis, muscles on radial artery, , 7. Ulnar pulse, , Over the little fingerside of wrist on ulnar artery, , 8. Femoral pulse, , In the groin on femoral artery, , 9. Popliteal pulse, , Behind knee, in the popliteal fossa on popliteal artery, , 10. Dorsalis pedis pulse, , Over the dorsum of foot on dorsalis pedis artery, , 11. Tibial pulse, , Over the back of the ankle, behind medial malleolus on posterior tibial artery, , EXAMINATION OF RADIAL PULSE, , 1. RATE, , Examination of pulse is a valuable clinical procedure., Pulse represents the heartbeat. By examining pulse,, important information regarding cardiac function such, as rate of contraction, rhythmicity, etc. can be obtained., In addition, an experienced physician can determine, the mean arterial pressure by hardness of pulse and its, amplitude., , Pulse rate is the number of pulse per minute. It has to, be counted at least for 30 seconds. Pulse rate in adults, is 72/minute., , Method of Examining Radial Pulse, Subject is made to sit comfortably with forearm placed, in mid or semi prone position, with wrist slightly flexed., The observer must stand by the right side of the subject., Tips of the middle three fingers (index finger, middle, finger and ring finger) are placed over the radial artery, below the wrist at the base of thumb. Light pressure is, applied by the fingers until the pulse is felt. If necessary,, the fingers are moved around till the pulse is felt., Index finger is used to occlude blood flow from, radial artery. Ring finger is used to occlude retrograde, flow of blood from ulnar artery through palmar arch., Middle finger is used to assess the pulse., Observations during Examination of Pulse, 1., 2., 3., 4., 5., 6., , Rate, Rhythm, Character, Volume, Condition of blood vessel wall, Delayed pulse., , Pulse Rate at Different Age, In fetus, At birth, At 10 years of age, After puberty, , :, :, :, :, , 150 to 180/minute, 130 to 140/minute, 90/minute, 72/minute., , Variations, Conditions that alter the heart rate alter pulse rate also., Pulse rate increases during:, i., ii., iii., iv., v., vi., vii., , Exercise, Pregnancy, Emotional conditions, Fever, Anemia, Hypersecretion of catecholamines, Hyperthyroidism., , Pulse rate decreases during:, i., ii., iii., iv., , Sleep, Hypothermia, Hypothyroidism, Incomplete heart block.
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Chapter 106 t Arterial Pulse 625, 2. RHYTHM, Rhythm is the regularity of pulse. It refers to interval, between beats. Under normal conditions, the pulse, appears at regular intervals. Rhythm of the pulse, becomes irregular in conditions like atrial fibrillation,, extrasystole and other types of arrhythmia (Chapter, 96)., Pulse with irregular rhythm is of two types:, i. Regularly irregular pulse, ii. Irregularly irregular pulse., 3. CHARACTER, Character denotes the tension on the vessel wall, produced by the waves of pulse. It is usually evaluated, at right carotid artery. Normally, it is not possible to detect, the different waves of the pulse or slight variations in, the character or form of the pulse. However, it becomes, more prominent in some abnormal conditions such as, anacrotic pulse, water hammer pulse, pulsus paradoxus,, etc. which are explained later in this chapter., 4. VOLUME, Volume is the determination of movement of the vessel, wall, produced by the transmission of pulse wave. It is, also a measure of pulse pressure. It depends upon the, condition of the blood vessel., 5. CONDITION OF THE BLOOD VESSEL WALL, Condition of wall of the blood vessel is assessed, by feeling the radial artery and rolling it against the, underlying bones. Normally, the wall of the vessel is not, palpable in children and young adults. However, in old, age the wall of the vessel becomes rigid and palpable., In abnormal conditions like arteriosclerosis, it is felt as, a hard rope., , in the arrival of femoral pulse indicates coarctation, (narrowing) of aorta. This delay is called femoral delay,, radial femoral delay or radiofemoral delay., ii. Radial-radial Delay, When both the radial pulses are examined simultaneously,, sometimes the arrival of pulse is delayed on one side., It is called radio-radial delay or radial-radial delay or, radial-radial inequality. This indicates the narrowing of, large artery due to atherosclerosis., , APPLIED PHYSIOLOGY –, ABNORMAL PULSE, 1. PULSUS DEFICIT, Pulsus deficit is the abnormal condition in which the, pulse rate is less than the heart rate. It occurs in atrial, fibrillation, when the stroke volume is reduced. Because, of reduced stroke volume, some of the pulse waves, become weak and disappear before reaching the, peripheral arteries. Pulsus deficit is the only condition in, which pulse rate is less than the heart rate., 2. PULSUS ALTERNANS, Pulsus alternans is the abnormal condition in which, the amplitude of every second wave in pulse tracing is, relatively smaller. It is because of the alternate variation in, the force of ventricular contraction. However, the rhythm of, the pulse is not altered. It is common in severe myocardial, diseases, paroxysmal tachycardia and atrial fibrillation., 3. ANACROTIC PULSE, Anacrotic pulse is the abnormal pulse, characterized, by a slow ascending limb which has a notch called, anacrotic notch. It is produced in aortic stenosis, when, ejection is slow., , 6. DELAYED PULSE, , 4. THREADY PULSE OR WEAK PULSE, , Sometimes, the arrival of pulse in certain peripheral, arteries is delayed. It is an important feature to be noted, because it is useful in diagnosis of certain diseases., Types of delayed pulse:, i. Femoral delay, ii. Radial-radial delay., , Thready or weak pulse is the abnormal pulse in which, the volume of pulse becomes very feeble and is, hardly felt at the arteries. It usually occurs whenever, the stroke volume decreases or when there is severe, vasoconstriction, as in the case of severe hemorrhage, or severe chills. In these conditions, the sympathetic, activity increases enormously, leading to generalized, vasoconstriction., , i. Femoral Delay, While palpating radial pulse and femoral pulse, simultaneously, there is a short delay in the arrival, of femoral pulse wave. Normally, it is negligible and, unnoticed. However, the prolonged or noticeable delay, , 5. PULSUS PARADOXUS, Pulsus paradoxus is the condition when the pulse, becomes very strong and very weak alternately, in
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626 Section 8 t Cardiovascular System, relation to respiratory cycle. Normally, there is a slight, increase in volume of pulse during inspiration and slight, decrease in volume during expiration. But, it is hardly, noticed. However, when it becomes very prominent,, it is pathological. This type of pulse is noticed in, cardiac tamponade (Chapter 100). It is also noticed in, physiological conditions such as deep breathing., 6. WATER HAMMER PULSE, Water hammer pulse is the abnormal pulse, characterized, by a rapid upstroke and an equally rapid downstroke. It, is also called collapsing or Corrigan pulse. It is seen, in conditions like aortic regurgitation, patent ductus, arteriosus and arteriovenous fistula. It is best felt by, raising the arm of the subject and holding it by grasping, the wrist with palm of the observer., 7. ABNORMAL PULSE IN PATENT, DUCTUS ARTERIOSUS, Patent ductus arteriosus is the permanent existence of, ductus arteriosus. In fetus, the lungs are nonfunctioning., So, the blood which is pumped by right ventricle into, the pulmonary artery, is diverted to systemic aorta, through ductus arteriosus. Ductus arteriosus closes, after birth. However, in some cases, it exists without, closing (Fig. 106.2)., Pulse pressure wave is very much altered in this, condition. Since, the blood flows from systemic aorta, , FIGURE 106.3: Radial pulse tracing in patent ductus, arteriosus and aortic regurgitation, , to pulmonary artery, after every ventricular systole,, the blood flows out of aorta quickly. It decreases the, diastolic pressure and the catacrotic limb of the pulse, tracing falls below the level of 80 mm Hg., Flow of blood from aorta to pulmonary artery, increases the venous return to left side of the heart. So,, left ventricular output increases, which in turn elevates, the systolic pressure in arteries. Thus, in pulse tracing,, the peak of the pulse wave is elevated above the level, of 120 mm Hg. So, the pulse tracing in this condition, reveals the increased pulse pressure (Fig. 106.3)., 8. ABNORMAL PULSE IN, AORTIC REGURGITATION, , FIGURE 106.2: Diagram showing ductus arteriosus, , Aortic regurgitation is the backflow of blood from aorta, into left ventricle. It is common during incompetence, of semilunar valve in aorta. It decreases the diastolic, pressure. Because of backflow of blood, the left, ventricular filling increases greatly, leading to increase, in output and systolic pressure. Thus, the pulse tracing, in aortic regurgitation is more or less similar to that in, patent ductus arteriosus. Only difference is that in the, tracing during aortic regurgitation, the incisura is very, mild. And in severe conditions, when the aortic valve, does not close, the incisura is absent (Fig. 106.3).
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Chapter, , Venous Pulse, , , , , , , , 107, , INTRODUCTION, SIGNIFICANCE, EXAMINATION OF VENOUS PULSE, METHODS TO RECORD VENOUS PULSE, RECORDING OF VENOUS PULSE – JUGULAR VENOUS PULSE TRACING, APPLIED PHYSIOLOGY – ABNORMAL VENOUS PULSE, , , , , ELEVATED JUGULAR VENOUS PULSE, KUSSMAUL SIGN, ABNORMALITIES OF WAVES IN JUGULAR PULSE TRACING, , INTRODUCTION, Venous pulse is defined as the pressure changes, transmitted in the form of waves from right atrium to, veins near heart. Venous pulse is observed only in, larger veins near the heart such as jugular vein., Observation of venous pulse is an integral part of, the physical examination because it reflects right atrial, pressure and the hemodynamic events in right atrium., , SIGNIFICANCE, 1. Venous pulse recording is used to determine the, rate of atrial contraction, just as the record of arterial, pulse is used to determine the rate of ventricular, contraction, 2. Many phases of cardiac cycle can be recognized by, means of venous pulse tracing, 3. Venous pulse tracing is the simple and accurate, method to measure the duration of different phases, in diastole, 4. Venous pulse also represents the atrial pressure, changes taking place during cardiac cycle., , EXAMINATION OF VENOUS PULSE, Inspection of jugular vein pulsations is routinely done by, bedside examination of neck veins. It provides valuable, information about the cardiac function., , To observe the pulsation of internal jugular vein,, head of the subject is tilted upwards at 45°. However,, in patients with increased venous pressure, the head, should be tilted as much as 90°. Pulsations of jugular, vein can be noticed when light is passed across the skin, overlying internal jugular vein with relaxed neck muscles., Simultaneous palpation of the left carotid artery helps, the examiner confirm the venous pulsations., , METHODS TO RECORD VENOUS PULSE, A small funnel covered by thin rubber membrane is placed, over the skin at the level of external jugular vein, in the, supraclavicular fossa. Slight pressure is exerted to provide, perfect contact between edge of the funnel and skin., Pressure changes in the vein cause some oscillations, in rubber membrane through the skin. The oscillations, are transmitted through rubber tube to a recording device, like Marey tambour. Nowadays, electronic transducer, is used for this purpose., The subject should be in such a position so as to, avoid the effect of gravity, which tends to empty veins, and reduce the amplitude of the venous pulse., , RECORDING OF VENOUS PULSE –, JUGULAR VENOUS PULSE TRACING, Recording of jugular venous pulse is called phlebogram., It is similar to intra-atrial pressure curve (Fig. 107.1).
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628 Section 8 t Cardiovascular System, , APPLIED PHYSIOLOGY –, ABNORMAL VENOUS PULSE, ELEVATED JUGULAR VENOUS PULSE, , FIGURE 107.1: Phlebogram, , Like intra-atrial pressure curve, phlebogram also, has three positive waves, namely a, c, v and three, negative waves namely x, x1, y., ‘a’ Wave, ‘a’ wave is the first positive wave. It is due to rise in atrial, pressure during atrial systole. It precedes ventricular, systole., ‘x’ Wave, ‘x’ wave is a negative wave due to fall in atrial pressure., It coincides with atrial diastole and beginning of, ventricular systole., , ‘c’ Wave, ‘c’ wave is a positive wave due to rise in atrial pressure, during isometric contraction period. During this period,, the atrioventricular valves bulge into the atria and, increase the pressure in the atria slightly., Earlier, it was thought that this wave was due to, transmission of pulse from neighboring carotid artery., Hence, it was called ‘c’ wave., ‘x1’ Wave, ‘x1’ wave is a negative wave due to fall in atrial pressure, during ejection period. During ejection period, the, atrioventricular ring is pulled towards ventricles causing, distention of atria. So, the atrial pressure falls., ‘v’ Wave, ‘v’ wave is a positive wave due to rise in atrial, pressure. The pressure increases because of filling of, atria (venous return). It is obtained during isometric, relaxation period or during atrial diastole., ‘y’ Wave, ‘y’ wave is a negative wave which denotes fall in, atrial pressure. Pressure falls due to the opening of, atrioventricular valve and emptying of blood into the, ventricle. This wave appears during rapid and slow, filling periods. ‘y’ wave is followed by ‘a’ wave and the, cycle is repeated., , Elevated jugular venous pulse indicates the rise in right, ventricular pressure., It occurs in:, 1. Bradycardia, 2. Pericardial effusion, 3. Constrictive pericarditis, 4. Tricuspid stenosis, 5. Pulmonary hypertension., KUSSMAUL SIGN, Kussmaul sign is the increase in venous distention and, venous pressure. Normally, it occurs during inspiration., Pathological Conditions when, Kussmaul Sign occurs, 1., 2., 3., 4., , Cardiac tamponade, Constrictive pericarditis, Restrictive cardiomyopathy, Right ventricular infarction., , ABNORMALITIES OF WAVES IN, JUGULAR PULSE TRACING, 1. Elevation of ‘a’ Wave, Elevation of ‘a’ wave occurs in:, i. Tricuspid stenosis, ii. Pulmonary hypertension., 2. Cannon ‘a’ Wave, Giant ‘a’ wave with abrupt fall (downward deflection) is, called Cannon ‘a’ wave. It appears in:, i. Complete heart block, ii. Paroxysmal atrioventricular nodal tachycardia, iii. Ventricular tachycardia., 3. Abnormal ‘v’ Wave, ‘v’ wave becomes abnormal in tricuspid incompetence., 4. Abnormal ‘x’ Wave, Abnormal ‘x’ wave appears in:, i. Atrial fibrillation, ii. Cardiac temponade, iii. Constrictive pericarditis., 5. Abnormal ‘y’ Wave, ‘y’ wave becomes abnormal in:, i. Tricuspid regurgitation, ii. Constrictive pericarditis.
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Coronary Circulation, , Chapter, , 108, , DISTRIBUTION OF CORONARY BLOOD VESSELS, , , , , CORONARY ARTERIES, VENOUS DRAINAGE, PHYSIOLOGICAL SHUNT, , CORONARY BLOOD FLOW AND ITS MEASUREMENT, , , , NORMAL CORONARY BLOOD FLOW, MEASUREMENT OF CORONARY BLOOD FLOW, , PHASIC CHANGES IN CORONARY BLOOD FLOW, , , , PHASIC CHANGES IN LEFT VENTRICLE, PHASIC CHANGES IN RIGHT VENTRICLE, , FACTORS REGULATING CORONARY BLOOD FLOW, , , , , , NEED FOR OXYGEN, METABOLIC FACTORS, CORONARY PERFUSION PRESSURE, NERVOUS FACTORS, , APPLIED PHYSIOLOGY – CORONARY ARTERY DISEASE, , , , , , CORONARY OCCLUSION, MYOCARDIAL ISCHEMIA AND NECROSIS, MYOCARDIAL INFARCTION – HEART ATTACK, CARDIAC PAIN – ANGINA PECTORIS, , DISTRIBUTION OF CORONARY, BLOOD VESSELS, CORONARY ARTERIES, Heart muscle is supplied by two coronary arteries,, namely right and left coronary arteries, which are the, first branches of aorta. Arteries encircle the heart in the, manner of a crown, hence the name coronary arteries, (Latin word corona = crown)., , Variations in Coronary Arteries, 1. In 50% to 60% of human beings, the right coronary, artery is larger (right dominant) and supplies more, blood to heart than left coronary artery, 2. In 15% to 20% of human beings, the left coronary, artery is larger (left dominant), 3. In 20% to 30% of human beings, both arteries, supply almost equal amount of blood., , Right and Left Coronary Arteries, , Branches of Coronary Arteries, , Right coronary artery supplies whole of the right, ventricle and posterior portion of left ventricle. Left, coronary artery supplies mainly the anterior and lateral, parts of left ventricle. There are many variations in, diameter of coronary arteries., , Coronary arteries divide and subdivide into smaller, branches, which run all along the surface of the heart., Smaller branches are called epicardiac arteries and, give rise to further smaller branches known as final, arteries or intramural vessels. Final arteries run at right
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630 Section 8 t Cardiovascular System, angles through the heart muscle, near the inner aspect, of wall of the heart., , Indirect Method, , VENOUS DRAINAGE, , Coronary blood flow is measured by applying Fick, principle (Chapter 98) using nitrous oxide (N2O). The, subject is asked to inhale a known quantity of the gas, with atmospheric air. Then, blood samples are collected, from an artery and from coronary sinus, by using a, catheter. The blood flow is determined by using the, formula:, , Venous drainage from heart muscle is by three types of, vessels., 1. Coronary Sinus, Coronary sinus is the larger vein draining 75% of total, coronary flow. It drains blood from left side of the heart, and opens into right atrium near tricuspid valve., 2. Anterior Coronary Veins, Anterior coronary veins drain blood from right side of the, heart and open directly into right atrium., 3. Thebesian Veins, Thebesian veins drain deoxygenated blood from, myocardium, directly into the concerned chamber of the, heart., PHYSIOLOGICAL SHUNT, Physiological shunt is the diverted route (diversion),, through which the venous (deoxygenated) blood is, mixed with arterial blood. Deoxygenated blood flowing, from thebesian veins into cardiac chambers makes up, the part of normal physiological shunt., Other component of physiological shunt is the drain, age of deoxygenated blood from bronchial circulation, into pulmonary vein, without being oxygenated. Refer, Chapter 119 for more details about physiological shunt., , 1. By Fick principle, , Blood flow =, , Amount of N2O taken up/minute, Arteriovenous difference of N2O content, , 2. By using Doppler flowmeter, Piezoelectric crystals are used in the Doppler, flowmeter probe, to transmit and receive the pulses of, high frequency sound waves (Chapter 98). The Doppler, flowmeter probe is mounted to a catheter and positioned, at the ostium of right or left coronary artery to measure, the velocity of phasic flow of blood. The cross-sectional, area of the artery is determined by angiography. From, velocity of blood flow and cross-sectional area, the, volume of blood flow is calculated., , 3. By videodensitometry, Videodensitometry is the technique used to measure, both velocity of blood flow and the cross-sectional area, of coronary arteries, simultaneously. From these two, values, the coronary blood flow can be calculated., , PHASIC CHANGES IN CORONARY, BLOOD FLOW, , Normal blood flow through coronary circulation is, about 200 mL/minute. It forms 4% of cardiac output. It, is about 65 to 70 mL/minute/100 g of cardiac muscle., , Blood flow through coronary arteries is not constant. It, decreases during systole and increases during diastole, (Fig. 108.1)., Intramural vessels or final arteries supplying, myocardium are perpendicular to the cardiac muscles., So, during systole, the intramural vessels are, compressed and blood flow is reduced. During diastole,, the compression is released and the blood vessels are, distended. So, the blood flow increases., , MEASUREMENT OF CORONARY, BLOOD FLOW, , PHASIC CHANGES IN, LEFT VENTRICLE, , CORONARY BLOOD FLOW, AND ITS MEASUREMENT, NORMAL CORONARY BLOOD FLOW, , Direct Method, Coronary blood flow is measured by using an, electromagnetic flowmeter. It is directly placed around, any coronary artery (refer Chapter 98 for details of, electromagnetic flowmeter)., , In left ventricle, during the onset of isometric contraction,, blood flow declines sharply due to two reasons, namely, increase in myocardial tissue pressure and decrease, in aortic pressure., During ejection period, rise in aortic pressure causes, a sharp rise in flow into left coronary artery. However,
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Chapter 108 t Coronary Circulation 631, Coronary blood flow is regulated mainly by local, vascular response to the needs of cardiac muscle., Factors regulating coronary blood flow:, 1. Need for oxygen, 2. Metabolic factors, 3. Coronary perfusion pressure, 4. Nervous factors., 1. NEED FOR OXYGEN, , FIGURE 108.1: Phasic changes in coronary blood flow, , the flow of blood through coronary capillaries is less., It is due to the high intramural myocardial pressure, in the contracting ventricle. Decreased blood flow is, maintained until the closure of aortic valve, i.e. till the, end of systole., During the onset of diastole, blood flow rises, and it reaches the peak sharply. During the later part, of diastole, the flow is reduced slightly along with, decreasing aortic pressure. Once again, there is a, sharp fall in flow during the onset of systole., PHASIC CHANGES IN, RIGHT VENTRICLE, A small amount of blood flows into right ventricle during, systole. It is because the force of contraction is not as, severe as in the case of left ventricle. Still, the amount, of blood flowing is very much less than that during, diastole., , FACTORS REGULATING, CORONARY BLOOD FLOW, Autoregulation, Like any other organ, heart also has the capacity to, regulate its own blood flow by autoregulation (Chapter, 102). Coronary blood flow is not affected when mean, arterial pressure varies between 60 and 150 mm Hg., Several factors are involved in the autoregulation, mechanism., , Oxygen is the most important factor maintaining blood, flow through the coronary blood vessels. Amount of, blood passing through coronary circulation is directly, proportional to the consumption of oxygen by cardiac, muscle., Even in resting condition, a large amount of, oxygen, i.e. 70% to 80% is consumed from the blood, by heart muscle than by any other tissues. In conditions, associated with increased cardiac activity, the need for, oxygen increases enormously., Thus, the need for oxygen, i.e. hypoxia immediately, causes coronary vasodilatation and increases the blood, flow to heart., 2. METABOLIC FACTORS, Coronary vasodilatation during hypoxic conditions, occurs because of some metabolic products, which, increase the coronary blood flow by vasodilatation., Reactive Hyperemia, Reactive hyperemia is the increase in blood flow due to, the vasodilator effects of metabolites., Metabolic Products which Increase, the Coronary Blood Flow, Adenosine, Adenosine is a potent vasodilator and it increases the, blood flow to cardiac muscle. During hypoxia, ATP in the, muscle is degraded in large amount, forming ADP. Some, ADP molecules are further degraded into adenosine,, which is released into tissue fluids of heart muscle., Other substances, Other substances which increase the coronary blood, flow by vasodilatation are:, i. Potassium, ii. Hydrogen, iii. Carbon dioxide, iv. Adenosine phosphate compounds.
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632 Section 8 t Cardiovascular System, 3. CORONARY PERFUSION PRESSURE, Perfusion pressure is the balance between mean, arterial pressure and venous pressure (Chapter 102)., Thus, coronary perfusion pressure is the balance, between mean arterial pressure in aorta and the right, atrial pressure. Since right aterial pressure is low, the, mean arterial pressure becomes the major factor that, maintains the coronary blood flow. Range of mean, arterial pressure at which the coronary blood flow can, be maintained is given above., 4. NERVOUS FACTORS, Coronary blood vessels are innervated both by para, sympathetic and sympathetic divisions of autonomic, nervous system. It is not known whether the autonomic, nerves have direct effect on blood flow in various, conditions. However, these nerves influence the coronary, blood flow indirectly by acting on the musculature of, heart., For example, stimulation of sympathetic nerves, increases the rate and force of contraction of heart. This, in turn, causes liberation of more metabolites which, dilate the blood vessels and increase the coronary, blood flow. Similarly, when parasympathetic nerves are, stimulated, the cardiac functions are inhibited and the, production of metabolites is less. Coronary blood flow, decreases., , APPLIED PHYSIOLOGY –, CORONARY ARTERY DISEASE, Coronary artery disease (CAD) is the heart disease, that is caused by inadequate blood supply to cardiac, muscle due to occlusion of coronary artery. It is also, called coronary heart disease., CORONARY OCCLUSION, Definition, Coronary occlusion is the partial or complete obstruction, of the coronary artery., , becomes narrow. In severe conditions, the artery is, completely occluded., Development of atherosclerotic plaque is common, in coronary arteries near the origin from aorta. This, plaque activates platelets, resulting in thrombosis and, the blood clot is called thrombus. When three fourth, of the lumen of the coronary artery is obstructed either, by atherosclerotic plaque or thrombus, the blood flow, to myocardium is reduced. It results in ischemia of, myocardium. Coronary thrombosis is associated with, spasm of coronary artery., Smaller blood vessels are occluded by the thrombus, or part of atherosclerotic plaque, detached from coronary, artery. This thrombus or part of the plaque is called, embolus., , MYOCARDIAL ISCHEMIA AND NECROSIS, Myocardial Ischemia, Myocardial ischemia is the reaction of a part of, myocardium in response to hypoxia. Hypoxia develops, when blood flow to a part of myocardium decreases, severely due to occlusion of a coronary artery., Blood flow is usually restored if a small quantum of, myocardium is affected by ischemia due to obstruction, of smaller blood vessels. It is due to rapid development, of coronary collateral arteries., Necrosis, Necrosis refers to death of cells or tissues by injury, or disease in a localized area. Ischemia leads to, necrosis of myocardium if a large part of myocardium, is involved or the occlusion is severe involving larger, blood vessels. Necrosis is irreversible., MYOCARDIAL INFARCTION –, HEART ATTACK, Myocardial infarction is the necrosis of myocardium, caused by insufficient blood flow due to embolus,, thrombus or vascular spasm. It is also called heart, attack. In myocardial infarction, death occurs rapidly, due to ventricular fibrillation., , Cause, Coronary occlusion is caused by atherosclerosis, a, condition associated with deposition of cholesterol on the, walls of the artery. In due course, this part of the arterial, wall becomes fibrotic and it is called atherosclerotic, plaque. The plaque is made up of cholesterol, calcium, and other substances from blood. Because of the, atherosclerotic plaque, the lumen of the coronary artery, , Myocardial Stunning, Myocardial stunning is a type of transient mechanical, dysfunction of heart, caused by a mild reduction in blood, flow. A substantial reduction in coronary blood flow, causes ischemia followed by necrosis. A mild reduction, in blood flow causes only ischemia and it may not be, sufficient to cause necrosis of myocardium. However,
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Chapter 108 t Coronary Circulation 633, it produces some transient (short lived) mechanical, disturbances or dysfunction of the heart. Since it is short, lived, heart recovers completely from this., Symptoms of Myocardial Infarction, Common symptoms of myocardial infarction:, 1. Cardiac pain, 2. Nausea, 3. Vomiting, 4. Palpitations, 5. Difficulty in breathing, 6. Extreme weakness, 7. Sweating, 8. Anxiety., CARDIAC PAIN – ANGINA PECTORIS, Cardiac pain is the chest pain that is caused by, myocardial ischemia. It is also called angina pectoris., It is the common manifestation of coronary artery, disease. Pain starts beneath the sternum and radiates, to the surface of left arm and left shoulder. Cardiac pain, is a referred pain and it is felt over the body, away from, heart. It is because, heart and left arm develop from the, same dermatomal segment in embryo., Cause for Cardiac Pain, Ischemia is mainly due to hypoxia. During myocardial, ischemia, there is accumulation of anaerobic metabolic, end products such as uric acid. Metabolites and other, pain producing substances like substance P, histamine, and kinin stimulate the sensory nerve endings, leading, to pain., , Chronic Angina Pectoris, In chronic angina pectoris, the patient does not feel the, pain normally. The pain is felt only when the workload, of heart increases. The workload of the heart increases, in conditions like exercise and emotional outburst., When the frequency of angina attack increases, the, patient is prone to develop acute myocardial infarction., Treatment for Angina Pectoris, 1. By using drugs, i. Vasodilator drugs: Vasodilator drugs like, glycerol trinitrate or sodium nitrite relieve the, pain by dilating coronary arteries. However, the, main therapeutic effect of such drugs is to dilate, splanchnic blood vessels, which cause reduction, in venous return, cardiac output, workload of the, heart and oxygen consumption in myocardium, so that, release of pain promoting substances is, inhibited., ii. Calcium channel blockers: These drugs block, the influx of calcium into the cells. When calcium, influx is blocked, the myocardial contractility and, workload of the heart are decreased., iii. Sympathetic blocking agents: Sympathetic, blocking agents like propranolol (beta blockers), block the betaadrenergic receptors and inhibit, the cardiac activity. This decreases heart rate,, stroke volume, workload on heart and oxygen, consumption. It also stops the production of, nociceptive substances in myocardium., 2. By thrombolysis, , Sensory Pathway, , Refer Chapter 98., , Sensory pathway from the heart is as follows:, 1. Inferior cervical sympathetic nerve fibers (Chapter, 101) carrying the sensations of pain (or stretch), from the heart reach the posterior gray horn of first, 4 thoracic segments of spinal cord, 2. Here, these fibers synapse with second order, neurons (substantial gelatinosa of Rolando) of, lateral spinothalamic tract, 3. Fibers from substantial gelatinosa of Rolando form, lateral spinothalamic tract and reach the sensory, cortex via thalamus., If hypoxia in myocardium is relieved by coronary, collateral circulation or by treatment, the pain producing, substances are washed away by blood flow., , 3. By surgical methods, i. Aortic-coronary artery bypass graft: Part of, myocardium affected by coronary occlusion is, detected by angiography. Then, the anastomosis, is made between aorta and the coronary artery, beyond occlusion, by a technique called aortic, coronary artery bypass graft. Mostly, a small vein, from lower limb is used for anastomosis. Though, this method can relieve the pain, it is not useful if, the myocardium is damaged extensively., ii. Percutaneous transluminal coronary angioplasty, (PTCA): Refer Chapter 98., iii. Laser coronary angioplasty: Refer Chapter 98.
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Cerebral Circulation, , Chapter, , 109, , INTRODUCTION, CEREBRAL VESSELS AND NORMAL CEREBRAL BLOOD FLOW, MEASUREMENT OF CEREBRAL BLOOD FLOW, , , , , , , KETY AND SCHMIDT NITROUS OXIDE METHOD, BY USING RADIOACTIVE SUBSTANCES, BY COMPUTERIZED AXIAL TOMOGRAPHY (CAT), BY POSITRON EMISSION TOMOGRAPHY (PET), BY MAGNETIC RESONANCE IMAGING (MRI), , REGULATION OF CEREBRAL BLOOD FLOW, , , , , AUTOREGULATION, CHEMICAL FACTORS, NERVOUS FACTORS, , APPLIED PHYSIOLOGY – STROKE, , INTRODUCTION, Brain tissues need adequate blood supply continuously., Stoppage of blood flow to brain for 5 seconds leads to, unconsciousness and for 5 minutes leads to irreparable, damage to the brain cells., , CEREBRAL VESSELS AND NORMAL, CEREBRAL BLOOD FLOW, Brain receives blood from the basilar artery and internal, carotid artery. Branches of these arteries form circle of, Willis. Venous drainage is by sinuses, which open into, internal jugular vein., , Normally, brain receives 750 to 800 mL of blood, per minute. It is about 15% to 16% of total cardiac, output and about 50 to 55 mL/100 g of brain tissue per, minute., , MEASUREMENT OF CEREBRAL, BLOOD FLOW, 1. KETY AND SCHMIDT NITROUS, OXIDE METHOD, Nitrous oxide method is an indirect method to measure, the blood flow to the brain. It is based on Fick principle, (Chapter 98). Nitrous oxide is used as an indicator, substance in this method., The subject is asked to inhale nitrous oxide at a low, concentration, which is less than the amount required, for anesthesia. After inhalation of the gas for about 10, minutes, the amount of nitrous oxide retained in the brain, tissues becomes equal to the amount of nitrous oxide, present in cerebral venous blood. Now, the concentration, of nitrous oxide is determined in the arterial blood and
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Chapter 109 t Cerebral Circulation 635, cerebral venous blood and the cerebral blood flow is, calculated by the formula:, Cerebral blood flow =, , Amount of N2O taken by brain, Arteriovenous difference of N2O, , 2. BY USING RADIOACTIVE SUBSTANCES, Radioactive substances method is used to determine, the amount of blood flow to different regions of the, cerebral cortex. Radioactive substance is injected into, the carotid artery. By measuring the radioactivity in the, brain tissues using radioactive detectors (scintillation, counter), the blood flowing through each area of brain, is determined. Advantage of this method is that the, blood flow to about 250 areas of cerebral cortex can, be measured by using many radioactive detectors., Radioactive xenon and 2-deoxyglucose are the, commonly used radioactive substances to measure, the cerebral blood flow., 3. BY COMPUTERIZED AXIAL TOMOGRAPHY, Computerized axial tomography (CT or CAT) scanning, was introduced in 1970s. Tomography scanning is, a process which combines many two dimensional, X-ray images to generate cross sectional pictures of, different organs or regions of the body. Advancement, of technology resulted in combination of many three, dimensional X-ray images of body structures and organs, including brain. CT scan of brain is useful to determine, brain damage and local changes in cerebral blood flow,, while the subject performs a task., 4. BY POSITRON EMISSION TOMOGRAPHY, Positron emission tomography (PET) scanner is a type, of computerized tomography machine. A short-lived, radioactive substance called radionuclide combined, with sugar is injected into the patient. Radionuclide, emits positrons (antiparticle or antimatter counterpart, of electron). Positron emissions from radionuclide are, detected by rotating the PET scanner around patient’s, head. PET is used to study blood volume, oxygen, consumption, pH, glucose utilization, blood flow and, the activity of receptors in brain cells., 5. BY MAGNETIC RESONANCE IMAGING, Magnetic resonance imaging (MRI) is a different type of, imaging technique. It involves polarization of hydrogen, atoms in the soft tissues by using a large magnet, , and detecting the resonant signals (summation of, the spinning energies within the living cells) from the, tissues. Since the images are very clear, this technique, is useful for scanning soft tissues, brain, spinal cord,, abdomen, joints and malignant tissues. MRI is also, used to measure blood flow to the organs such as brain., Measurement of blood flow to a part or area of the, organ is called functional magnetic resonance imaging, (fMRI)., , REGULATION OF CEREBRAL, BLOOD FLOW, Cerebral circulation is regulated by three factors:, 1. Autoregulation, 2. Chemical factors, 3. Neural factors., AUTOREGULATION, Like any other vital organ, brain also regulates its own, blood flow by means of autoregulation (Chapter 102)., However, the autoregulation in brain has got its own, limitations. It depends upon:, i. Effective perfusion pressure, ii. Cerebral vascular resistance., Cerebral blood flow is directly proportional to the, balance between effective perfusion pressure and the, vascular resistance in brain., i. Effective Perfusion Pressure, Effective perfusion pressure is the balance between, the mean arterial blood pressure and venous pressure, across the organ, divided by resistance (Chapter 102)., Since venous pressure is zero in brain, mean arterial, blood pressure plays an important role in regulating, cerebral blood flow. Autoregulation is possible in brain, if the mean arterial pressure is within the range of, 60 mm Hg and 140 mm Hg. Autoregulation fails beyond, this range on either side., ii. Cerebral Vascular Resistance, When the vascular resistance is more, the blood flow, to the brain is less. Resistance to blood flow in brain, is offered by intracranial pressure, cerebrospinal fluid, pressure and viscosity of blood., Intracranial pressure and cerebrospinal fluid pressure, Increase in the intracranial pressure or the pressure, exerted by the cerebrospinal fluid (CSF) compresses, the cerebral blood vessels and decreases blood flow., These pressures are elevated in conditions like head
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636 Section 8 t Cardiovascular System, injury. However, severe ischemic effects are avoided by, some protective reflexes such as Cushing reflex., Cushing reflex, Cushing reflex is a protective reflex that helps save the, brain tissues from ischemic effects during the periods, of reduced cerebral blood flow. It is also called Cushing, reaction, response or phenomenon., Increase in intracranial pressure or increase in, CSF pressure compresses the cerebral blood vessels, and decreases the blood flow. However, blood flow, is decreased only for a short period. It is restored, immediately by means of Cushing reflex. When cerebral, blood flow decreases by the compression of cerebral, arteries, the cerebral ischemia develops. Compression, of blood vessels decreases the blood flow to vasomotor, center also. Local hypoxia and hypercapnea activate, vasomotor center, resulting in peripheral vasoconstriction, and rise in the arterial pressure. The increased arterial, pressure helps to restore the cerebral blood flow., Thus, Cushing reflex plays the most important role in, maintaining the cerebral blood flow (Fig. 109.1)., Cushing reflex operates only when the rise in arterial, blood pressure is proportional to increase in intracranial, pressure. When the increase in intracranial pressure is, very high and if it exceeds the arterial blood pressure, this, , protective mechanism fails. And the cerebral ischemia, becomes severe, leading to irreversible damage of the, brain tissues., Monro-Kellie doctrine, According to Monro-Kellie doctrine or principle, though, the cerebral arteries are compressed by increased, intracranial pressure or cerebrospinal fluid pressure,, the volume of brain tissue is not affected. It is because, the brain tissue is not compressible., Viscosity, Increase in the viscosity of blood as in polycythemia,, increases the cerebral vascular resistance and blood, flow decreases. When viscosity decreases as in the, case of anemia, the resistance is decreased and blood, flow increases. Thus, the cerebral blood flow is inversely, proportional to the viscosity of blood., CHEMICAL FACTORS, Chemical factors which increase the cerebral blood, flow:, i. Decreased oxygen tension, ii. Increased carbon dioxide tension, iii. Increased hydrogen ion concentration., Carbon dioxide is the most important factor, as it, causes dilatation of cerebral blood vessels, leading to, increase in blood flow. A moderate increase in carbon, dioxide tension does not alter the blood flow due to, autoregulation. When arterial partial pressure of carbon, dioxide rises above 45 mm Hg, the cerebral blood flow, increases., Carbon dioxide combines with water to form, carbonic acid, which dissociates into bicarbonate ions, and hydrogen ion. The hydrogen ion causes dilatation, of blood vessels in brain., Hypoxia increases cerebral blood flow by, vasodilatation., NERVOUS FACTORS, , FIGURE 109.1: Schematic representation of Cushing reflex., CSF = Cerebrospinal fluid., , Cerebral blood vessels are supplied by sympathetic, vasoconstrictor fibers. But, these fibers do not play, any role in regulating cerebral blood flow under normal, conditions. In pathological conditions like hypertension,, the sympathetic nerves cause constriction of cerebral, blood vessels, leading to reduction in blood flow. It, prevents cerebral vascular hemorrhage and cerebral, stroke.
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Chapter 109 t Cerebral Circulation 637, , APPLIED PHYSIOLOGY – STROKE, Definition, Stroke is the sudden death of neurons in localized, area of brain due to inadequate blood supply. It is, characterized by reversible or irreversible paralysis with, other symptoms. Stroke is also called cardiovascular, accident (CVA) or brain attack., Types, Stroke is classified into two types:, 1. Ischemic stroke, which occurs due to interruption, of blood flow to a part of brain by thrombus or, atherosclerotic embolus, 2. Hemorrhagic stroke, which develops by the rupture, of a blood vessel in the brain and spilling of blood, into the surrounding areas., Causes, Most common factors (risk factors) which causes stroke, are:, , 1., 2., 3., 4., 5., 6., , Heart disease, Hypertension, High cholesterol in blood, High blood sugar (diabetes mellitus), Heavy smoking, Heavy alcohol consumption., , Symptoms, Symptoms of stroke depend upon the area of brain that, is damaged. Generally, stroke causes dizziness, loss of, consciousness, coma or death., Other features of stroke:, 1. Weakness, 2. Numbness or paralysis, particularly on one side of, the body, 3. Impairment of speech, 4. Emotional disturbances, 5. Loss of coordination, 6. Loss of memory.
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Splanchnic Circulation, , Chapter, , 110, , INTRODUCTION, MESENTERIC CIRCULATION, , , , DISTRIBUTION OF BLOOD FLOW, REGULATION OF MESENTERIC BLOOD FLOW, , SPLENIC CIRCULATION, , , , , IMPORTANCE OF SPLENIC CIRCULATION, STORAGE OF BLOOD, REGULATION OF BLOOD FLOW TO SPLEEN, , HEPATIC CIRCULATION, , , , , BLOOD VESSELS, NORMAL BLOOD FLOW, REGULATION OF BLOOD FLOW TO LIVER, , INTRODUCTION, , 1. Local Autoregulation, , Splanchnic or visceral circulation constitutes three, portions:, 1. Mesenteric circulation supplying blood to GI tract, 2. Splenic circulation supplying blood to spleen, 3. Hepatic circulation supplying blood to liver., Unique feature of splanchnic circulation is that the, blood from mesenteric bed and spleen forms a major, amount of blood flowing to liver. Blood flows to liver from, GI tract and spleen through portal system., , Local autoregulation is the primary factor regulating, blood flow through mesenteric bed (Chapter 102)., , MESENTERIC CIRCULATION, , 3. Nervous Factor, , DISTRIBUTION OF BLOOD FLOW, Stomach : 35 mL/100 g/minute, Intestine : 50 mL/100 g/minute, Pancreas : 80 mL/100 g/minute., REGULATION OF MESENTERIC, BLOOD FLOW, Mesenteric blood flow is regulated by the following, factors:, , 2. Activity of Gastrointestinal Tract, Contraction of the wall of the GI tract reduces blood flow, due to compression of blood vessels. And relaxation of, wall of GI tract increases the blood flow due to removal, of compression on the vessel wall., , Mesenteric blood flow is regulated by sympathetic nerve, fibers. Increase in sympathetic activity as in the case, of emotional conditions or ‘fight and flight reactions’, constrict the mesenteric blood vessels. So, more blood, is diverted to organs like skeletal muscles, heart and, brain, which need more blood during these conditions., Parasympathetic nerves do not have any direct action, on the mesenteric blood vessels. But these nerves, increase the contraction of GI tract which compresses, the blood vessels, resulting in reduction in blood flow.
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Chapter 110 t Splanchnic Circulation 639, 4. Chemical Factors – Functional Hyperemia, , NORMAL BLOOD FLOW, , Functional hyperemia is the increase in mesenteric, blood flow immediately after food intake. It is mainly, because of gastrin and cholecystokinin secreted after, food intake. In addition to these two GI hormones,, digestive products of food substances such as glucose, and fatty acids also cause vasodilatation and increase, the mesenteric blood flow., , Liver receives maximum amount of blood as compared to, any other organ in the body since, most of the metabolic, activities are carried out in the liver. Blood flow to liver, is 1,500 mL/minute, which forms 30% of the cardiac, output. It is about 100 mL/100 g of tissue/minute., Normally, about 1,100 mL of blood flows through, portal vein and remaining 400 mL of blood flows through, hepatic artery. However, portal vein carries only about, 25% of oxygen to liver. It is because it carries the blood,, which has already passed through the blood vessels of, GI tract, where oxygen might have been used. Hepatic, artery transports 75% of oxygen to the liver., , SPLENIC CIRCULATION, IMPORTANCE OF SPLENIC CIRCULATION, Spleen is the main reservoir for blood. Due to the, dilatation of blood vessels, a large amount of blood is, stored in spleen. And the constriction of blood vessels by, sympathetic stimulation releases blood into circulation., STORAGE OF BLOOD, In spleen, two structures are involved in storage of, blood, namely splenic venous sinuses and splenic, pulp (Chapter 25)., Small arteries and arterioles open directly into the, venous sinuses. When spleen distends, sinuses swell, and large quantity of blood is stored. Capillaries of, splenic pulp are highly permeable. So, most of the blood, cells pass through capillary membrane and are stored, in the pulp., Venous sinuses and the pulp are lined with, reticuloendothelial cells., , REGULATION OF BLOOD FLOW TO LIVER, Blood flow to liver is regulated by the following factors:, 1. Systemic Blood Pressure, Systemic blood pressure is the important factor, responsible for blood flow to liver and hepatic blood flow, is directly proportional to systemic blood pressure., 2. Splenic Contraction, During splenic, increases., , contraction,, , blood, , flow, , to, , liver, , 3. Movements of Intestine, Motility of intestine increases hepatic blood flow., 4. Chemical Factors, , Blood flow to spleen is regulated by sympathetic nerve, fibers., , Chemical factors which increase the blood flow to liver, by vasodilatation are:, i. Excess carbon dioxide, ii. Lack of oxygen, iii. Increase in hydrogen ion concentration., , HEPATIC CIRCULATION, , 5. Nervous Factors, , BLOOD VESSELS, , Sympathetic fibers to liver cause vasoconstriction in, liver and decrease the blood flow., Sympathetic fibers to liver and other portions of, splanchnic circulation pass through splanchnic nerve., Role of parasympathetic fibers in hepatic circulation is, not known., , REGULATION OF BLOOD FLOW, TO SPLEEN, , Liver receives blood from two sources:, 1. Hepatic artery, 2. Portal vein., More details are given in Chapter 40.
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Capillary Circulation, , Chapter, , 111, , INTRODUCTION, , , , , , MICROCIRCULATION, FEATURES OF CAPILLARIES, DIMENSIONS OF CAPILLARIES, VELOCITY AND VOLUME OF BLOOD FLOW, , STRUCTURE OF CAPILLARIES, , , , ENDOTHELIAL CELLS, PERICYTES, , PATTERN OF CAPILLARY SYSTEM, , , , , PREFERENTIAL CHANNELS, TRUE CAPILLARIES, ANATOMICAL AND PHYSIOLOGICAL SHUNTS, , PECULIARITIES OF CAPILLARY BLOOD FLOW, FUNCTIONS OF CAPILLARIES, , , , , DIFFUSION, FILTRATION, PINOCYTOSIS, , FACTORS CONTROLLING CAPILLARY CIRCULATION, , , , NERVOUS FACTORS, CHEMICAL FACTORS, , INTRODUCTION, MICROCIRCULATION, Microcirculation refers to flow of blood through the, minute blood vessels such as arterioles, capillaries and, venules. Capillary circulation forms the major part of, microcirculation. Human body contains about 10 billion, capillaries., Study of Capillary Circulation, Blood flow through capillaries is studied by focusing the, capillaries under dissecting microscope. Frog’s web,, mesentery of mammals and fingernail bed of humans, can be observed by using microscope., , FEATURES OF CAPILLARIES, 1. Capillaries arise from arterioles and form the actual, functional area of circulatory system, i.e. exchange, of materials between blood and tissues, 2. Structurally, capillaries are very narrow and short., However, quantitatively, these vessels outnumber, the other blood vessels. About 10 billion capillaries, are present in the body., 3. Each capillary lies in a very close proximity to the, cells of the tissues at a distance of about 20 to, 30 mm. This enables easy and rapid exchange of, substances between blood and the tissues through, interstitial fluid.
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Chapter 111 t Capillary Circulation 641, DIMENSIONS OF CAPILLARIES, Dimensions of capillaries are given in Table 111.1., TABLE 111.1: Dimensions and details of capillaries, Dimensions/Details, , Normal value, , Total number of capillaries, , 10 billion, , Surface area of all capillaries, , 500 to 700 sq m, , Average length, , 0.5 to 1 mm, , Average diameter, , 8µ, , Pressure at arterial end, , 30 to 32 mm Hg, , Pressure at venous end, , 14 to 16 mm Hg, , Velocity of blood flow, , 0.05 cm/second, , VELOCITY AND VOLUME OF BLOOD FLOW, Average velocity of blood flow through capillaries is, 0.05 cm/second. About 5% of total blood is present in, capillaries., , STRUCTURE OF CAPILLARIES, Capillaries are formed by single layer of endothelial, cells, which are wrapped around by pericytes., ENDOTHELIAL CELLS, Endothelial cells of the capillaries are thin, flattened,, nucleated polygonal cells joined together by a cement, substance., Capillaries do not have muscular coat. Yet, these, blood vessels actively modify their own diameter in, response to nervous, hormonal, chemical and physical, stimuli. Endothelial cells themselves alter the diameter, of capillaries by swelling or shrinking., In most of the capillaries, adjacent endothelial cells, leave a cleft called fenestra through which several, substances may traverse the endothelium by means of, transcytosis (Fig. 111.1). However, in cerebral capillaries, the fenestra are absent because the endothelial cells, fuse to each other by tight junctions (Chapter 163)., , and secrete several vasoactive agents, growth factors,, extracellular matrix and components of basement, membrane. Pericytes are also involved in regulation of, blood flow through endothelial junctions particularly in, conditions such as inflammation., , PATTERN OF CAPILLARY SYSTEM, Capillaries are disposed between arterioles and venules., From the arterioles, the meta-arterioles take origin (Fig., 111.2). From meta-arterioles, two types of capillaries, arise:, 1. Preferential channels, 2. True capillaries., 1. PREFERENTIAL CHANNELS, Preferential channels are also called continuous, capillaries. After arising from meta-arterioles, these, capillaries form a network and finally join the venules., Preferential channels or continuous capillaries have, same diameter as meta-arterioles., 2. TRUE CAPILLARIES, True capillaries also form a network and join the venules., Diameter of the true capillaries is less than that of the, meta-arterioles., Precapillary Sphincter, Beginning of true capillaries is encircled by smooth, muscle fibers. It functions as a sphincter; so it is known, as precapillary sphincter. It controls the blood flow, through true capillaries., ANATOMICAL AND PHYSIOLOGICAL SHUNTS, Anatomical Shunt, Anatomical shunt is the direct link between arterioles, and venules. It is also called arteriovenous shunt. Flow, , PERICYTES, Pericyte is a perivascular mesenchymal like cell associated with walls of small blood vessels such as capillaries, and postcapillary vessels. It is similar to renal mesangial, cell. It is also known as mural cell or Rouget cell (named, after the discoverer Charles Rouget)., Pericytes extend long cytoplasmic processes,, which wrap around the endothelial cells. Pericytes, play important role in remodeling and maintenance of, capillary system. These cells are contractile in nature, , FIGURE 111.1: Cross section of capillary
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642 Section 8 t Cardiovascular System, , FIGURE 111.2: Capillary bed, , of blood through the capillaries where exchange of, nutrients, gases and other substances takes place is, called nutritional flow. Blood flow through anatomical, shunt is called non-nutritional flow. Non-nutritional blood, flow occurs in many tissues of the body particularly, during resting conditions when metabolic activities are, low., Physiological Shunt, Physiological shunt is the link between arterial and, venous side of circulation provided by meta-arteriole., Many tissues of the body such as muscles do not have, anatomical shunts. However, the meta-arteriole in these, tissues acts as the physiological shunt between arterial, and venous sides of the circulation. Non-nutritional blood, flow occurs through physiological shunt under resting, conditions., , 2., 3., , 4., 5., 6., , triction and dilatation of meta-arterioles and the alternate opening and closure of precapillary sphincters., Direction of blood flow through capillaries is not fixed, as in the case of other blood vessels. Blood may flow, in opposite direction in two adjacent capillaries., In capillaries, blood flows as a single pile or single, row of blood cells. In other blood vessels, the blood, flows in either axial stream containing mainly blood, cells or peripheral stream containing plasma., Under resting conditions, most of the capillaries, lie in collapsed state. Only during activity, all the, capillaries open up and increase the vascularity., Amount of blood flowing through the capillary system, throughout the body is very low. It is only about, 150 mL/minute., Velocity of blood flow is least in capillaries. It is only, about 0.05 cm/second. It facilitates exchange of, substances between capillaries and tissues., , Shunt in Capillaries Vs Shunt in Heart, , FUNCTIONS OF CAPILLARIES, , Physiological shunt in capillaries is different from, physiological shunt in heart. In capillaries, the oxygenated, blood flows towards deoxygenated blood. But in heart,, the deoxygenated blood flows towards the oxygenated, blood (Chapter 108)., , Most important function of capillaries is the exchange, of substances between blood and tissues. Oxygen,, nutrients and other essential substances enter the, tissues from capillary blood; carbon dioxide, metabolites, and other unwanted substances are removed from the, tissues by capillary blood., Exchange of materials across the capillary endothelium occurs by the following processes:, 1. Diffusion, 2. Filtration, 3. Pinocytosis., , PECULIARITIES OF CAPILLARY, BLOOD FLOW, 1. Blood does not pass through capillary system, continuously. It is because of the alternate cons-
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Chapter 111 t Capillary Circulation 643, DIFFUSION, , PINOCYTOSIS, , Diffusion is the main process for exchange of gases,, water, glucose, sodium, urea and many other substances. These substances diffuse through the intercellular clefts present in the endothelial wall of the capillaries., Diffusion occurs because of concentration gradient, across the capillary wall., , Larger molecules are transported across the capillary, endothelium in the form of vesicles. Large molecules, are packed as vesicles in the capillary endothelial cells., These vesicles are transported across the endothelial, membrane by the process called pinocytosis (Chapter 3)., , FILTRATION, Site of filtration of substances through capillary membrane varies in different organs. In skeletal muscles,, cardiac muscles, kidneys and intestine, filtration occurs, through the slit pores present in capillary endothelium., Capillaries in other organs have discontinued endothelium through which filtration occurs., Filtration of substances through capillary endothelium, depends upon the net filtration pressure. Net filtration, pressure is the balance between the driving pressures, and the opposing pressures. It is well explained by, Starling hypothesis (Chapter 52). Process of filtration is, explained in Chapter 27., , FACTORS CONTROLLING, CAPILLARY CIRCULATION, Capillary blood flow is controlled by the nervous and, chemical factors., NERVOUS FACTORS, Capillaries are mainly supplied by the sympathetic vasoconstrictor fibers., CHEMICAL FACTORS, Many chemical factors such as excess of carbon dioxide, increased hydrogen ion concentration, lack of, oxygen, histamine and metabolites like lactic acid cause, dilatation of capillaries. Serotonin causes constriction of, capillaries.
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Circulation through, Skeletal Muscle, , Chapter, , 112, , INTRODUCTION, FACTORS REGULATING BLOOD FLOW TO SKELETAL MUSCLE, , , , , MECHANICAL FACTORS, CHEMICAL FACTORS, NERVOUS FACTORS, , APPLIED PHYSIOLOGY – VARICOSE VEINS, , INTRODUCTION, , NERVOUS FACTORS, , During resting condition, blood flow to skeletal muscle, is 4 to 7 mL/100 g/minute. During exercise, it increases, to about 100 mL/100 g/minute., , Blood vessels of the skeletal muscles are mostly, innervated by sympathetic nerve fibers and few para, sympathetic nerve fibers are also seen. Special feature, of sympathetic nerve fibers supplying the skeletal, muscles is that these nerve fibers are vasodilators and, not constrictors. Since the sympathetic nerve fibers, cause dilatation of blood vessels in muscle by secreting, acetylcholine, these nerve fibers are called sympathetic, vasodilator fibers or sympathetic cholinergic fibers., , FACTORS REGULATING BLOOD, FLOW TO SKELETAL MUSCLE, Blood flow through skeletal muscle is regulated by, three factors:, 1. Mechanical factors, 2. Chemical factors, 3. Nervous factors., MECHANICAL FACTORS, During contraction of the muscle, blood vessels are, compressed and the blood flow decreases. And during, relaxation of the muscle, compression of blood vessels, is relieved and the blood flow increases., In severe muscular exercise, blood flow increases, in between the muscular contractions., CHEMICAL FACTORS, Important chemical factors, which regulate the blood, flow through skeletal muscles, are lack of oxygen,, excess of carbon dioxide and increased hydrogen ion, concentration. All these chemical factors increase the, blood flow to muscle by causing vasodilatation., , APPLIED PHYSIOLOGY –, VARICOSE VEINS, Varicose vein is the vein that becomes irregularly swollen, (twisted or tortuous) and enlarged. Superficial veins of, the leg are mostly affected., Causes for Varicose Vein, 1. Permanent dilatation of veins due to incompetence, of the valves of the veins or absence of muscular, activity for long periods. So, varicose veins are, common in the individuals with occupations, which, require standing for long periods., 2. Thrombophlebitis (inflammation of vein associated, with formation of thrombus).
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Chapter 112 t Circulation through Skeletal Muscle 645, Varicose veins may also develop in obese persons, and pregnant women., Varicose Vein in Obesity, Obesity is the major factor for varicose veins. Excess fat, increases the pressure on veins of legs and aggravate, the condition., , Varicose Vein in Pregnancy, During pregnancy, varicose veins develop because of, two reasons:, 1. Increased blood level of progesterone, which dilates, the blood vessel, 2. Enlarged uterus, which compresses the major veins in, pelvic region leading to increase in venous pressure.
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Cutaneous Circulation, , , , , , , Chapter, , 113, , ARCHITECTURE OF CUTANEOUS BLOOD VESSELS, FUNCTIONS OF CUTANEOUS CIRCULATION, NORMAL BLOOD FLOW TO SKIN, REGULATION OF CUTANEOUS BLOOD FLOW, APPLIED PHYSIOLOGY – VASCULAR RESPONSES OF SKIN TO MECHANICAL STIMULI, , , , WHITE REACTION, LEWIS TRIPLE RESPONSE, , ARCHITECTURE OF CUTANEOUS, BLOOD VESSELS, Architecture of cutaneous blood vessels is formed in the, following manner:, 1. Arterioles arising from the smaller arteries reach, the base of papillae of dermis (Chapter 60), 2. Then, these arterioles turn horizontally and give rise, to meta-arterioles, 3. From meta-arterioles, hairpin-shaped capillary, loops arise. Arterial limb of the loop ascends, vertically in the papillae and turns to form a venous, limb, which descends down., 4. After reaching the base of papillae, few venous limbs, of neighboring papillae unite to form the collecting, venule, , 5. Collecting venules anastomose with one another to, form the subpapillary venous plexus, 6. Subpapillary plexus runs horizontally beneath the, bases of papillae and drain into deeper veins., , FUNCTIONS OF CUTANEOUS, CIRCULATION, Cutaneous blood flow performs two functions:, 1. Supply of nutrition to skin, 2. Regulation of body temperature by heat loss., , NORMAL BLOOD FLOW TO SKIN, Under normal conditions, the blood flow to skin is, about 250 mL/square meter/minute. When the body, , temperature increases, cutaneous blood flow increases, up to 2,800 mL/square meter/minute because of cutaneous vasodilatation., , REGULATION OF CUTANEOUS, BLOOD FLOW, Cutaneous blood flow is regulated mainly by body, temperature. Hypothalamus plays an important role in, regulating cutaneous blood flow., When body temperature increases, the hypothalamus is activated. Hypothalamus in turn causes, cutaneous vasodilatation by acting through medullary, vasomotor center. Now, blood flow increases in skin., Increase in cutaneous blood flow causes the loss of heat, from the body through sweat. When body temperature, is low, vasoconstriction occurs in the skin. Therefore,, the blood flow to skin decreases and prevents the heat, loss from skin., , APPLIED PHYSIOLOGY –, VASCULAR RESPONSES OF SKIN, TO MECHANICAL STIMULI, Vascular responses of skin are the reactions developed, in blood vessels of skin when some mechanical stimuli, are applied over the surface of it., Vascular responses of skin are of two types:, A. White reaction, B. Lewis triple response.
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Chapter 113 t Cutaneous Circulation 647, WHITE REACTION, White reaction is the response of the blood vessels, in skin to a mechanical stimulus. When the surface of, skin is stroked lightly with a pointed object, a pale line, appears within 20 seconds. This line takes the path, of the stroke. This response in skin is known as white, reaction. Maximum intensity of the line is obtained in 1, minute and it fades away after 5 minutes., White reaction is due to the constriction of, cutaneous capillaries. Capillaries constrict because, of the local stimulation of capillary wall and exertion of, tension upon capillary wall. No nervous factor is involved, in this process., LEWIS TRIPLE RESPONSE, Lewis triple response is the vascular response of skin that, includes three consecutive reactions of blood vessels, of skin to a mechanical stimulus. It was discovered by, Lewis Sir Thomas in 1927. He noticed that the vascular, reactions of skin to various injuries occur in three stages, and named these reactions as triple response., Three reactions of this response:, 1. Red reaction, 2. Flare, 3. Wheal., 1. Red Reaction, Red reaction is the appearance of a red line when a, pointed instrument is drawn firmly over the surface of, the skin. This reaction occurs over the line of the stroke., Red reaction appears within 15 seconds after the stroke., It obtains the maximum intensity at the end of 1 minute, and disappears later gradually., Red reaction is because of dilatation of capillaries, due to mechanical stimulus. This reaction is purely a local, response. It occurs due to the release of histamine-like, substance from the tissues damaged by the stimulus., Lewis called it ‘H’ substance., Red reaction does not depend upon nervous factors., It occurs even after the sectioning or degeneration of, nerves of skin., 2. Flare, If the stroke is applied with little more force or if the, stroke is repeated on the same line, the red reaction, spreads around the line of stroke. It spreads for about, 10 cm from the line of stroke, depending upon the force, applied. This is called flare or spreading flush. Flare, appears within 30 seconds after appearance of red, line. It also disappears later. Flare is due to dilatation of, arterioles. It depends upon nervous mechanism and is, due to axon reflex., , FIGURE 113.1: Axon reflex during flare, , Axon Reflex, Axon reflex or antidromic reflex is the process by which, the impulses are conducted in a direction opposite to the, normal direction. Normally, the impulses produced by a, cutaneous pain receptor pass through sensory nerve, fiber towards the nerve cell body in posterior nerve, root ganglion. Some of these impulses pass through, the other branches of the same fiber in the opposite, direction and reach the blood vessels supplied by these, branches. Impulses now dilate the blood vessels. This, is called the antidromic or axon reflex (Fig. 113.1)., Nerve fibers transmitting the impulses in the opposite, direction are called antidromic vasodilator fibers., Flare occurs if the main trunk of nerves is cut. It, does not occur when the nerves degenerate., 3. Wheal, When intensity of stimulus is severe, the surface of skin, on the line of stroke is interrupted. A small elevation or, swelling is seen in the surrounding area up to a height, of 2 mm. It is called wheal or local edema., Wheal appears within 3 minutes after the stimulus, and it replaces the red line. Maximum height is obtained, within 5 minutes and it disappears after several hours., Wheal appears due to the leakage of fluid from, capillaries. The permeability of capillary membrane, is increased. Wheal does not depend upon nervous, mechanism., Dermographism, The process of embossing signs over skin is called, dermographism. It is also called writing on skin. Some, letters or designs can be embossed upon the skin over, back or in the forearm in the same manner by which the, wheal is produced.
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Chapter, , Fetal Circulation, and Respiration, , , , , , 114, , INTRODUCTION, BLOOD VESSELS IN FETUS, FETAL LUNGS, CHANGES IN CIRCULATION AND RESPIRATION AFTER, BIRTH – NEONATAL CIRCULATION AND RESPIRATION, , , , , , , , FIRST BREATH OF THE CHILD, FLOW OF BLOOD TO LUNGS, CLOSURE OF FORAMEN OVALE, REVERSAL OF BLOOD FLOW IN DUCTUS ARTERIOSUS, CLOSURE OF DUCTUS VENOSUS, CLOSURE OF DUCTUS ARTERIOSUS, , INTRODUCTION, Fetal circulation is different from that of adults because, of the presence of placenta. Since fetal lungs are nonfunctioning, placenta is responsible for exchange of, gases between fetal blood and mother’s blood. So, the, blood from right ventricle is diverted to placenta., Development of heart is completed at 4th week of, intrauterine life and it starts beating at the rate of 65, per minute. Along with heart, the blood vessels also, develop. Heart rate gradually increases and reaches, the maximum rate of about 140 beats per minute just, before birth., Fetus is connected with the mother through, placenta. Fetal blood passes to placenta through, umbilical vessels and the maternal blood runs through, uterine vessels. These two sets of blood vessels lie in, close proximity in the placenta through which exchange, of substances takes place between mother’s blood and, fetal blood. However, there is no direct admixture of, maternal and fetal blood (Fig. 114.1)., , BLOOD VESSELS IN FETUS, As fetal lungs are non-functioning, there is no necessity, of large amount of blood to be pumped into lungs., Instead, the fetal heart pumps large quantity of blood, into the placenta for exchange of substances. From, , placenta, the umbilical veins collect the blood, which, has more oxygen and nutrients. Umbilical vein passes, through liver. Some amount of blood is supplied to liver, from umbilical vein. However, a large quantity of blood, is diverted from umbilical vein into the inferior vena, cava through ductus venosus. Liver receives blood, from portal vein also., In liver, the oxygenated blood mixes slightly with, deoxygenated blood and enters the right atrium via, inferior vena cava. From right atrium, major portion, of blood is diverted into left atrium via foramen ovale., Foramen ovale is an opening in intra-atrial septum., Blood from upper part of the body enters the right, atrium through superior vena cava. From right atrium,, blood enters right ventricle. From here, blood is pumped, into pulmonary artery. From pulmonary artery, blood, enters the systemic aorta through ductus arteriosus., Only a small quantity of blood is supplied to fetal, lungs. Blood from left ventricle is pumped into aorta., Fifty percent of blood from aorta reaches the placenta, through umbilical arteries., , FETAL LUNGS, Pulmonary vascular resistance is the resistance offer-, , ed to blood flow through pulmonary vascular bed. This, resistance is very high in fetus because of the non-
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Chapter 114 t Fetal Circulation and Respiration 649, , FIGURE 114.1: Fetal circulation, , functioning of fetal lungs. The high resistance in fetal, lungs increases the pressure in the blood vessels, of lungs. Because of the high pressure, the blood is, diverted from pulmonary artery into aorta via ductus, arteriosus., , CHANGES IN CIRCULATION AND, RESPIRATION AFTER BIRTH – NEONATAL, CIRCULATION AND RESPIRATION, 1. FIRST BREATH OF THE CHILD, When fetus is delivered and umbilical cord is cut and tied,, the lungs start functioning. When placental blood flow is, cut off, there is sudden hypoxia and hypercapnia. Now,, , the respiratory center is strongly stimulated by these, two factors and the respiration starts. Initially, there is, gasping, which is followed by normal respiration., 2. FLOW OF BLOOD TO LUNGS, Lungs expand during the first breath of the infant., Expansion of lungs causes immediate reduction in the, pulmonary vascular resistance and a sudden fall in, pressure in the blood vessels of lungs. Therefore, the, blood flow from pulmonary artery to lungs increases., 3. CLOSURE OF FORAMEN OVALE, When blood starts flowing through the pulmonary circu, lation, the oxygenated blood from the lungs returns to
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650 Section 8 t Cardiovascular System, , FIGURE 114.2: Fetal, neonatal and adult circulation. RA = Right atrium, LA = Left atrium, RV = Right ventricle,, LV = Left ventricle, FO = Foramen ovale, DA = Ductus arteriosus, SVC = Superior vena cava, IVC = Inferior, vena cava, Dashed blue line (Fetal circulation) indicates flow of very less quantity of blood., , left atrium. It causes increase in the left atrial pressure., Simultaneously, due to stoppage of blood from placenta,, pressure in inferior vena cava is decreased. It leads to, fall in right atrial pressure. Thus, the pressure in right, atrium is less and the pressure in left atrium is already, high. This causes the closure of foramen ovale. Within, few days after birth, the foramen ovale closes completely, and fuses with the atrial wall., , nary aorta (Fig. 114.2). The reversed flow in ductus arteriosus is heard as continuous murmur in infants., , 4. REVERSAL OF BLOOD FLOW, IN DUCTUS ARTERIOSUS, , 6. CLOSURE OF DUCTUS ARTERIOSUS, , In fetus, since pulmonary arterial pressure is very high,, the blood passes from pulmonary artery into aorta via, ductus arteriosus. However, in neonatal life, since the, systemic arterial pressure is more than pulmonary, arterial pressure, the blood passes in opposite direction, in ductus arteriosus, i.e. from systemic aorta into pulmo-, , 5. CLOSURE OF DUCTUS VENOSUS, Due to the contraction of smooth muscle near junction, between umbilical vein and ductus venosus, the constriction and closure of ductus venosus occurs. Later, the, ductus venosus becomes fibrous band., , Ductus arteriosus starts closing due to narrowing., It closes completely after 2 days and the adult type, of circulation starts. In some rare cases, the ductus, arteriosus does not close. It remains intact producing, a continuous murmur. This condition with intact ductus, arteriosus is known as patent ductus arteriosus (Refer, to Chapter 106).
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Chapter, , Hemorrhage, , 115, , DEFINITION, TYPES AND CAUSES OF HEMORRHAGE, , , , , , , ACCIDENTAL HEMORRHAGE, CAPILLARY HEMORRHAGE, INTERNAL HEMORRHAGE, POSTPARTUM HEMORRHAGE, HEMORRHAGE DUE TO PREMATURE DETACHMENT OF PLACENTA, , COMPENSATORY EFFECTS OF HEMORRHAGE, , , , IMMEDIATE COMPENSATORY EFFECTS OF HEMORRHAGE, DELAYED COMPENSATORY EFFECTS OF HEMORRHAGE, , DEFINITION, , 3. INTERNAL HEMORRHAGE, , Hemorrhage is defined as the excess loss of blood due, to rupture of blood vessels., , Internal hemorrhage is the bleeding in viscera. It is, caused by rupture of blood vessels in the viscera. The, blood accumulates in viscera., , TYPES AND CAUSES OF HEMORRHAGE, Hemorrhage occurs due to various reasons. Based on the, cause, hemorrhage is classified into five categories:, 1. ACCIDENTAL HEMORRHAGE, Accidental hemorrhage occurs in road accidents and, industrial accidents, which are very common in the, developed and developing countries., Accidental hemorrhage is of two types:, i. Primary hemorrhage, which occurs immediately, after the accident, ii. Secondary hemorrhage, which takes place, sometime (about few hours) after the accident., 2. CAPILLARY HEMORRHAGE, Capillary hemorrhage is the bleeding due to the rupture, of blood vessels, particularly capillaries. It is very, common in brain (cerebral hemorrhage) and heart during, cardiovascular diseases. The rupture of the capillary is, followed by spilling of blood into the surrounding areas., , 4. POSTPARTUM HEMORRHAGE, Excess bleeding that occurs immediately after labor, (delivery of the baby) is called postpartum hemorrhage., In some cases, it is very severe and leads to major, complications., 5. HEMORRHAGE DUE TO PREMATURE, DETACHMENT OF PLACENTA, In some cases, the placenta is detached from the uterus, of mother before the due date of delivery causing severe, hemorrhage., , COMPENSATORY EFFECTS, OF HEMORRHAGE, Many effects are observed during and after hemorrhage., Effects are different in acute hemorrhage and chronic, hemorrhage.
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652 Section 8 t Cardiovascular System, Acute Hemorrhage, Acute hemorrhage is the sudden loss of large quantity of, blood. It occurs in conditions like accidents. Decreased, blood volume in acute hemorrhage causes hypovolemic, shock (Chapter 116)., Chronic Hemorrhage, Chronic hemorrhage is the loss of blood either by, internal or by external bleeding over a long period of, time. Internal bleeding occurs in conditions like ulcer., External bleeding occurs in conditions like hemophilia, and excess vaginal bleeding (menorrhagia). Chronic, hemorrhage produces different types of effects such as, anemia., Compensatory Effects, After hemorrhage, series of compensatory reactions, develop in the body to cope up with the blood loss., Compensatory effects of hemorrhage are of two, types., A. Immediate compensatory effects, B. Delayed compensatory effects., IMMEDIATE COMPENSATORY EFFECTS, OF HEMORRHAGE, 1. On Cardiovascular System, Reduced blood volume after hemorrhage decreases, venous return, ventricular filling and cardiac output. In, severe hemorrhage, there is fall in blood pressure also., However, when blood loss is slow or less, the arterial, blood pressure is not affected much. If it is affected it is, restored quickly., During mild hemorrhage, During slow or mild hemorrhage when there is loss of, a small amount of blood up to 350 to 500 mL the blood, pressure decreases slightly and soon it returns back to, normal., Mechanism involved in maintenance of blood, pressure:, i. Usually when arterial blood pressure increases,, the carotid and aortic baroreceptors are stimu, lated and send impulses to brain resulting, in decrease in blood pressure (Chapter, 103). During hemorrhage when the arterial, blood pressure falls, baroreceptors become, inactivated and stop discharging impulses., ii. This increases the vasomotor tone leading to, vasoconstriction. This type of reflex vasocons, triction occurs in all regions of the body except, brain and heart., , iii. Vasoconstriction results in increase in the peri, pheral resistance, iv. Loss of blood also causes reflex constriction of, veins, v. Venoconstriction enhances the venous return,, ventricular filling and stroke volume, vi. Thus, because of increased peripheral resis, tance and stroke volume the arterial blood, pressure is restored, vii. One more factor is involved in this mechanism., Vasoconstriction occurs in the organs having, reservoir function such as skin, liver and spleen., Blood from these reservoir organs is directed into, systemic circulation. This may compensate the, volume of blood that is lost during hemorrhage., During severe hemorrhage, When hemorrhage is severe with loss of about 1,500 to, 2,000 mL of blood, the arterial blood pressure falls to a, great extend. It is because of decreased venous return, and stroke volume., In the heart, the reflex tachycardia increases the, quantity of metabolic products in myocardium. These, metabolic products cause coronary vasodilatation., 2. On Skin, Vasoconstriction in skin, which occurs after hemorrhage, decreases the cutaneous blood flow. It increases the, deoxygenation of blood and large quantity of reduced, hemoglobin is accumulated in cutaneous blood vessels., It results in greyish pallor color of skin., Sometimes cyanosis develops in certain areas of, the body. Skin also becomes cold due to less blood flow., Sweating is decreased., 3. On Tissue Fluid, Arteriolar constriction decreases the capillary pres, sure. Therefore, tissue fluid enters capillaries. It, helps to compensate the blood loss. It also causes, hemodilution., , 4. On Kidneys, Constriction of afferent and efferent arterioles of kidneys, after hemorrhage decreases the glomerular filtration, rate (GFR) very much. Therefore, the urinary output, decreases. The blood level of nitrogenous substances,, particularly urea, increases resulting in uremia., Severe hemorrhage leads to fall in arterial blood, pressure and damage of renal tubules resulting in acute, renal failure., , 5. On Renin Secretion, Hypoxia produced after blood loss increases secretion, of renin from kidney and the subsequent formation of
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Chapter 115 t Hemorrhage 653, angiotensin II. Angiotensin II helps in restoring blood, pressure by producing generalized vasoconstriction., It also increases release of aldosterone from adrenal, cortex. Aldosterone causes retention of sodium and this, helps increasing the blood pressure. Angiotensins III, and IV are also involved in restoring the blood pressure, (Chapter 50)., 6. On Secretion of Antidiuretic Hormone, Antidiuretic hormone (ADH) is released in large quantities, immediately after the hemorrhage. It is probably due to, increased osmolality of body fluid by aldosterone induced, sodium retention. ADH promotes water retention and, helps in restoring osmolality and volume of ECF., 7. On Secretion of Catecholamines, Sympathetic activity increases due to blood loss. It, causes secretion of large quantities of catecholamines,, which are also involved in restoring blood pressure by, the vasoconstrictor effect., 8. On Respiration, Hemorrhage causes stagnant hypoxia because of, decrease in venous return, cardiac output and velocity, of blood flow. Hypoxia stimulates the chemoreceptors, leading to increase in respiratory rate. The catecho, lamines, which are secreted in large quantities due, to hemorrhage, increase the respiratory movements, through reticular activating system (RAS)., 9. On Nervous System, i. On brain, Though hemorrhage causes vasoconstriction in many, organs of the body, it causes vasodilatation in brain. It, is because of increased sympathetic activity. However,, the blood flow to brain is not affected very much after, hemorrhage because of autoregulation., ii. On reticular formation, Catecholamines stimulate the RAS. It causes restless, ness, anxiety and increased motor activity after hemorr, hage. The respiratory movements are also accelerated, due to stimulation of RAS., iii. Fainting, When hemorrhage is severe, cardiac output decreases, and blood pressure falls. The autoregulation in brain, , fails to cope up with the hypotension. So, the blood flow, to brain decreases resulting in fainting (refer Chapter, 116 for details)., iv. Cerebral ischemia, When the blood flow to brain is severely affected due to, hypoxia, ischemia of the brain tissues develops within 5, minutes. It causes irreversible damage to brain tissues., DELAYED COMPENSATORY EFFECTS, OF HEMORRHAGE, If hemorrhage is not severe, some delayed compen, satory reactions occur. These reactions help to restore, blood volume, blood pressure and blood flow to different, regions of the body., Delayed reactions are:, 1. Restoration of plasma volume, 2. Restoration of plasma proteins, 3. Restoration of red blood cell count and hemoglobin, content., 1. Restoration of Plasma Volume, During the period of hemorrhage itself, tissue fluid starts, entering the blood because of low capillary pressure., So, the plasma volume increases., Because of increase in plasma volume, hemodilution, occurs. So, the concentration of plasma proteins and, hemoglobin is low. Transport of fluid from tissues is, continued for long time after hemorrhage., 2. Restoration of Plasma Proteins, The reserve proteins stored in liver start mobilizing, within few hours after hemorrhage. Liver also starts, synthesizing the plasma proteins. Restoration of plasma, proteins occurs within 3 to 4 days. Plasma proteins help, to retain the fluid transported from tissues to blood., 3. Restoration of Red Blood Cell Count, and Hemoglobin Content, Hypoxia that is developed after hemorrhage stimu, lates the secretion of erythropoietin from kidney. Eryth, ropoietin in turn stimulates red bone marrow causing, erythropoiesis. However, restoration of RBC count is a, slow process. It takes about 4 to 6 weeks. Reticulocyte, count increases in blood., Hemoglobin content also comes back to normal, level along with RBC count, if the diet contains adequate, quantity of iron and proteins.
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Circulatory Shock and, Heart Failure, , Chapter, , 116, , DEFINITION, MANIFESTATIONS OF CIRCULATORY SHOCK, STAGES OF CIRCULATORY SHOCK, , , , , FIRST STAGE OR COMPENSATED STAGE, SECOND STAGE OR PROGRESSIVE STAGE, THIRD STAGE OR IRREVERSIBLE STAGE, , TYPES AND CAUSES OF CIRCULATORY SHOCK, , , , , , SHOCK DUE TO DECREASED BLOOD VOLUME, SHOCK DUE TO INCREASED VASCULAR CAPACITY, SHOCK DUE TO CARDIAC DISEASES, SHOCK DUE TO OBSTRUCTION OF BLOOD FLOW, , TREATMENT FOR CIRCULATORY SHOCK, , , , , , , , , BLOOD TRANSFUSION, PLASMA TRANSFUSION, ADMINISTRATION OF PLASMA SUBSTITUTES, ADMINISTRATION OF SYMPATHOMIMETIC DRUGS, ADMINISTRATION OF GLUCOCORTICOIDS, OXYGEN THERAPY, BY CHANGING THE POSTURE, , HEART FAILURE, , , , , , , INTRODUCTION, CAUSES, SIGNS AND SYMPTOMS, TYPES, COMPENSATED VERSUS DECOMPENSATED HEART FAILURE, , DEFINITION, Shock is a general term that refers to the depression or, suppression of body functions produced by any disorder., Circulatory shock refers to the shock developed by, inadequate blood flow throughout the body. It is a lifethreatening condition and it may result in death if the, affected person is not treated immediately., , MANIFESTATIONS OF, CIRCULATORY SHOCK, Characteristic feature of all types of circulatory shock, is the insufficient blood flow to the tissues particularly, , the brain. Major cause of decreased blood flow is the, reduction in cardiac output., Following are the manifestations of circulatory, shock:, 1. Whenever cardiac output is decreased, arterial, blood pressure drops down, 2. Low blood pressure produces reflex tachycardia, and reflex vasoconstriction, 3. Tachycardia decreases the diastolic period. So,, filling of the heart reduces leading to decrease, in stroke volume and systolic pressure. This, decreases the pulse pressure below 20 mm Hg., Pulse also becomes feeble.
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Chapter 116 t Circulatory Shock and Heart Failure 655, 4. Stagnant hypoxia develops because of decreased, velocity of blood flow, 5. Skin becomes pale and cold due to the vaso, constriction, 6. Along with hypoxia, cyanosis also develops in, many parts of the body, particularly ear lobes and, fingertips, 7. Glomerular filtration rate (GFR) and urinary output, are reduced due to fall in blood pressure and, constriction of renal blood vessels, 8. Metabolic activities of myocardium are accelerated, because of reduced blood flow and increased heart, rate. A large amount of lactic acid is produced,, resulting in acidosis., 9. Acidosis decreases myocardial efficiency and pumping action of the heart leading to further reduction in, cardiac output, 10. So, the blood flow to vital organs is severely, affected, 11. Lack of blood flow to brain tissues produces ischemia, resulting in fainting and irreparable damage of brain, tissues, 12. Finally the damage of brain tissues and cardiac, arrest kill the victim., , STAGES OF CIRCULATORY SHOCK, Circulatory shock occurs in three stages:, 1. First stage or compensated stage, 2. Second stage or progressive stage, 3. Third stage or irreversible stage., FIRST STAGE OR COMPENSATED STAGE, First stage is also called non-progressive stage. When, blood loss is less than 10% of total volume, the blood, pressure decreases only moderately. And the regulatory, mechanisms in the body operate successfully to re, establish normal blood pressure and normal blood, flow throughout the body. Thus the shock becomes, nonprogressive and the person recovers. Regulatory, mechanisms involve negative feedback control., Regulatory mechanisms are:, i. Baroreceptor mechanism, ii. Renal mechanism, iii. ADH mechanism., i. Baroreceptor Mechanism, Ischemic response by baroreceptors initiates strong, sympathetic stimulation, which causes vasoconstriction, and tachycardia (Fig. 116.1)., ii. Renal Mechanism, Kidneys release large amount of renin that increases, the angiotensin II formation. Angiotensin II produces, , intense vasoconstriction and increases release of, aldosterone from adrenal cortex. Aldosterone in turn, promotes retention of water and salts by kidneys. This, helps in restoration of blood volume., iii. ADH Mechanism, Antidiuretic hormone (ADH) released from posterior, pituitary increases retention of water by kidneys. ADH, also enhances vasoconstriction., Because of severe vasoconstriction caused by, the regulatory mechanisms, normal blood pressure is, re-established. Retention of water by kidneys and the, consequent fluid shift mechanism that moves water, from interstitial space and intestinal lumen restores, the blood volume. And the person recovers if shock, is not severe enough to progress further. With proper, treatment, the progression can be arrested completely., SECOND STAGE OR PROGRESSIVE STAGE, Second stage is also called decompensated stage. When, the shock is severe, positive feedback system develops, so that regulatory mechanisms become inadequate to, compensate. And the shock enters progressive stage., With immediate and appropriate treatment, this stage of, shock can be reversed., During this stage, blood pressure falls to a low level,, which is not adequate to maintain the blood flow to, cardiac muscle. So the myocardium starts deteriorating, because of lack of nutrition and oxygen. Toxic substances, released from tissues also suppress the myocardium., Particularly, the bacterial toxin called endotoxin affects, the myocardium severely (Fig. 116.2)., Loss of blood flow also causes suppression of, vasomotor system and the sympathetic system. This, causes further fall in blood pressure. Due to low, pressure, thrombosis starts in small blood vessels like, capillaries. Now the capillary permeability increases, allowing passage of fluid from blood vessels into, interstitial space. Finally because of tissue deterioration, severe symptoms start appearing. And the shock, progresses to irreversible stage., THIRD STAGE OR IRREVERSIBLE STAGE, Third stage is the last stage prior to the collapse. It is, also called refractory stage. Irreversible stage leads, to death regardless of type of treatment offered to the, patient. It is because the brain fails to function due to, severe cerebral ischemia. The blood pressure falls, drastically. Even the infusion of blood fails to restore, blood pressure. Finally, cardiac failure occurs due, to decrease in the myocardial activity and reduced, arteriolar tone resulting in death of the affected person., Details of this stage are given in Figure 116.3.
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656 Section 8 t Cardiovascular System, , FIGURE 116.1: Compensated stage of circulatory shock. ADH = Antidiuretic hormone.
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Chapter 116 t Circulatory Shock and Heart Failure 657, , FIGURE 116.2: Progressive stage of circulatory shock
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658 Section 8 t Cardiovascular System, , FIGURE 116.3: Irreversible stage of circulatory shock
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Chapter 116 t Circulatory Shock and Heart Failure 659, , TYPES AND CAUSES OF, CIRCULATORY SHOCK, , 1. Hemorrhagic Shock, , Circulatory shock is primarily classified into four types, (Fig. 116.4)., A. Shock due to decreased blood volume, B. Shock due to increased vascular capacity, C. Shock due to cardiac disease, D. Shock due to obstruction of blood flow., SHOCK DUE TO DECREASED BLOOD, VOLUME – HYPOVOLEMIC SHOCK, Shock due to decreased blood volume is called, hypovolemic shock or cold shock. It occurs when there is, acute loss of at least 10% to 15% of blood. Loss of blood, less than 10% may not produce any significant effect, because of immediate compensatory mechanism., Important Manifestations of Hypovolemic Shock, 1., 2., 3., 4., 5., 6., , Decrease in cardiac output, Low blood pressure, Thin thready pulse, Pale and cold skin, Increase in respiratory rate, Restlessness or lethargy., , Pathological Conditions when Hypovolemic, Shock Occurs, 1., 2., 3., 4., 5., , Hemorrhage: Hemorrhagic shock, Trauma: Traumatic shock, Surgery: Surgical shock, Burns: Burn shock, Dehydration: Dehydration shock., , Hemorrhagic shock is the shock due to hemorrhage., Acute hemorrhage as in the case of accident causes, shock. Chronic hemorrhage as in ulcers does not, produce shock. Details of effects of hemorrhage are, given in the Chapter 115., 2. Traumatic Shock, Trauma means serious injury or wound caused by, , some external force. Shock caused by trauma is called, traumatic shock. Shock occurs due to the damage of, muscles and bones, which is common in battlefields, and road accidents. Apart from loss of blood, the, plasma escapes to the tissue spaces., Following are the common symptoms of traumatic, shock:, Crush syndrome, , Crush syndrome is the condition characterized by, renal failure when the limb of a person is crushed or, compressed in traumatic condition. Myoglobin and, some toxic substances released from affected muscles, damage the renal tubular cells leading to degeneration, of renal tubules. Stimulation of somatic afferents from, the damaged muscles causes constriction of renal blood, vessels. All these factors result in renal failure., Reperfusion injury, Reperfusion injury refers to dysfunction of myocardium,, blood vessels or any other tissue, which is induced by, restoration of blood flow to previously ischemic tissue., It is also called injury by reperfusion., Due to compression or damage during traumatic, conditions, the ischemic tissues release some toxic, substances. Later, when blood supply is restored to the, , FIGURE 116.4: Different types of circulatory shock
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660 Section 8 t Cardiovascular System, tissues again, the toxic substances enter the tissues, and cause further damage of the tissues. Common, instance is myocardial reperfusion injury., 3. Surgical Shock, Surgical shock is the shock developed by surgical, procedures. Surgical shock develops due to some, reasons like internal hemorrhage, external hemorrhage, and dehydration that occur during or after surgical, procedures., 4. Burn Shock, Burn shock is the shock produced by the effects of burn., In burns, loss of plasma through the burnt surface is more, than the loss of whole blood. It decreases the ECF volume, and plasma volume, resulting in hemoconcentration., This leads to sluggish blood flow, which decreases the, cerebral blood flow causing shock., 5. Dehydration Shock, Shock due to dehydration is called dehydration shock., Dehydration means decrease in water content of the, body. It decreases the blood volume resulting in shock., Refer Chapter 6 for the causes of dehydration., SHOCK DUE TO INCREASED VASCULAR, CAPACITY – VASOGENIC SHOCK, In this case, the blood volume is normal. Shock occurs, because of inadequate blood supply to the tissues, due to increased vascular capacity. Capacity of the, vascular system increases by the extensive dilatation, of blood vessels. It is also known as vasogenic or low, resistance or distributive shock., Causes and Types of Vasogenic Shock, 1. Sudden loss of vasomotor tone: Neurogenic shock, 2. Anaphylaxis: Anaphylactic shock, 3. Sepsis: Septic shock., 1. Neurogenic Shock, Neurogenic shock is the type of shock characterized by, sudden depression of nervous system due to extensive, vasodilatation caused by loss of vasomotor tone., Conditions when neurogenic shock develops, i. Ischemia of brain: Severe ischemia in medulla, depresses the activity of vasomotor center, ii. General anesthesia, iii. Spinal anesthesia, iv. Emotional conditions: Extreme emotions cause, sudden and exaggerated activity of autonomic, , nervous system, the subject faints because of, neurogenic shock., Syncope (Fainting), Syncope or fainting is the sudden and transient (shorttime) loss of consciousness and postural tone with, spontaneous recovery. It occurs due to temporary, inadequate cerebral blood flow., Types of syncope:, i. Vasovagal syncope or emotional fainting:, Fainting is caused by sudden stimulation of, vagus nerve. It is also called neurocardiogenic, syncope. It is due to extreme activation of, parasympathetic division of autonomic nervous, system. There is sudden decrease in heart, rate (bradycardia) because of inhibition of, myocardium by vagus. At the same time, the, blood pressure also decreases (hypotension), due to severe vasodilatation by the, parasympathetic nerve fibers (Fig. 116.5)., Simultaneously, sympathetic tone is decreased, and it also causes vasodilatation leading to, hypotension., Because of bradycardia and hypotension,, the cerebral blood flow decreases. This results, in fainting. Vasovagal syncope is common in, conditions like severe emotional distress and, exertion., ii. Postural syncope: Loss of consciousness, because of prolonged standing. It is due to, pooling of blood in lower limbs during prolonged, standing resulting in decreased blood supply to, the brain., iii. Micturition syncope: Fainting during micturition., It is common in the patients who suffer from, orthostatic hypotension. Fall in blood pressure, while standing is called orthostatic hypotension, (Chapter 103)., iv. Effort syncope: Fainting caused during exercise, or any other strain. It is the common symptom in, the patients with stenosis of semilunar valves., These patients faint during exercise or any, other physical strain. It is due to the failure of, the heart to increase the cardiac output, when, the tissues need more blood flow., v. Cough syncope: Fainting while coughing. Sometimes, severe cough increases intrathoracic, pressure, which reduces the venous return and, cardiac output leading to fainting., vi. Carotid sinus syncope: Fainting in persons, wearing dress with tight collar. Tight collar of, the dress exerts pressure over the region of, carotid sinus. This leads to reduction in heart, rate, vasodilatation and fainting.
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Chapter 116 t Circulatory Shock and Heart Failure 661, Conditions when septic shock occurs, i. Infection of the uterus and fallopian tube, commonly, occurring in abortion by instrumentation, ii. Infection of peritoneum, iii. Spreading of skin infection due to bacteria like, streptococci or staphylococci, iv. Spread of infection from any other part of the, body., Septic shock develops due to the depression of, myocardium, dilatation of blood vessels and increased, permeability of capillary membrane. All these effects, occur due to the toxic substances released by bacteria., Septic shock is also called as vasogenic, cardiogenic, or hypovolemic shock., Endotoxin shock, Endotoxin shock is the shock developed by a bacterial, toxin called endotoxin. Endotoxin is a lipopolysaccharide., It causes vasodilatation and depresses myocardial, activity. It also activates the macrophages to release, cytokines. Endotoxin shock is very common during the, infection of alimentary tract by gram-negative bacteria, like colon bacilli. It is actually released from dead, bacteria. Endotoxin shock can also occur in urinary tract, infection., SHOCK DUE TO CARDIAC DISEASES –, CARDIOGENIC SHOCK, Shock due to cardiac disease is also called cardiogenic, shock., FIGURE 116.5: Schematic representation, of vasovagal syncope, , 2. Anaphylactic Shock, , Conditions when Cardiogenic Shock Occurs, 1. Arrhythmia, particularly those which lead to reduced, cardiac output, 2. Depressed activity of myocardium due to ischemia, 3. Congestive cardiac disease., , Anaphylaxis means exaggerated allergic reaction to a, foreign protein or antigen or any other substance to which, the person has been previously sensitized (Chapter 17)., Shock that develops during anaphylactic reactions is, called anaphylactic shock. Shock occurs because of, vasodilatation and sudden fall in blood pressure. It is, caused by the chemical mediators such as histamine, that are secreted during anaphylactic reaction., , SHOCK DUE TO OBSTRUCTION OF, BLOOD FLOW – OBSTRUCTIVE SHOCK, , 3. Septic Shock, , Conditions when Obstructive Shock Occurs, , Sepsis is the pathological condition characterized by, , the presence of pathogenic organisms or their toxins, in blood or tissues. Shock developed during sepsis is, known as septic shock or blood poisoning., , Shock developed due to the obstruction of blood flow, through circulatory system is called obstructive shock., , 1. Tumor in myocardium, 2. Cardiac tamponade (Chapter 100), 3. Obstruction of blood vessels in lungs due to, embolism.
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662 Section 8 t Cardiovascular System, , TREATMENT FOR CIRCULATORY SHOCK, , BY CHANGING THE POSTURE, , Treatment for shock is based on the cause of the shock., Following are the various measures taken during the, treatment of shock., , This is the first measure to be taken in cases of, hemorrhagic and neurogenic shock. The head down, position (by raising the bed at the foot end) increases, venous return, cardiac output and cerebral blood flow., However, this should not be used for longer periods, because prolonged head down position might affect, the ventilation. It is because of effect of the increased, pressure exerted by abdominal viscera on diaphragm., , BLOOD TRANSFUSION, Transfusion of whole blood is done in hypovolemic, shock except burn shock., PLASMA TRANSFUSION, Plasma transfusion is very useful in burns or other, shocks in which there is loss of more plasma., , HEART FAILURE, INTRODUCTION, , Plasma substitute is a solution of a substance that, is used for transfusion instead of plasma. Plasma, substitutes are used when plasma is not available., , Heart failure or cardiac failure is the condition in which, the heart looses the ability to pump sufficient amount of, blood to all parts of the body. Heart failure may involve, left ventricle or right ventricle or both. It may be acute, or chronic., , Commonly used Plasma Substitutes, , Acute Heart Failure, , ADMINISTRATION OF PLASMA SUBSTITUTES, , i. Plasma expanders (solutions of sugar with, high molecular weight such as dextran); such, substances do not escape through capillary, membrane, ii. Concentrated human serum albumin, iii. Hypertonic solutions, which cause drawing of, fluid into blood from interstitial space., ADMINISTRATION OF, SYMPATHOMIMETIC DRUGS, Sympathomimetic drugs like epinephrine and norepine, phrine are useful in neurogenic and anaphylactic, shocks, which occur due to vasodilatation. These two, drugs restore the blood pressure by vasoconstriction., However, the sympathomimetic drugs should not, be used for longer period since, these drugs induce, severe myocardial activity. In traumatic and cardiogenic, shocks, dopamine is used., ADMINISTRATION OF GLUCOCORTICOIDS, Glucocorticoids are administered in serious conditions., Glucocorticoids increase the glucose metabolism in, damaged tissues, prevent further damage of tissues, and increase the myocardial activity., OXYGEN THERAPY, Oxygen therapy is given only in severe conditions, involving reduced oxygenation of tissues., , Acute heart failure refers to sudden and rapid onset of, signs and symptoms of abnormal heart functions. Its, symptoms are severe initially. However, the symptoms, last for a very short time and the condition improves, rapidly. Usually it requires treatment., Chronic Heart Failure, Chronic heart failure is the heart failure that is charac, terized by the symptoms that appear slowly over a, period of time and become worst gradually., Congestive Heart Failure, Congestive heart failure is a general term used to, describe the heart failure resulting in accumulation of, fluid in lungs and other tissues. When heart is not able, to pump blood through aorta, the blood remains in heart., It results in dilatation of the chambers and accumulation, of blood in veins (vascular congestion). Fluid retention, and pulmonary edema also occur in this condition., CAUSES OF HEART FAILURE, Common causes of heart failure are:, 1. Coronary artery disease, 2. Defective heart valves, 3. Arrhythmia, 4. Cardiac muscle disease such as cardiomyopathy, 5. Hypertension, 6. Congenital heart disease
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Chapter 116 t Circulatory Shock and Heart Failure 663, 7., 8., 9., 10., 11., , Diabetes, Hyperthyroidism, Anemia, Lung disorders, Inflammation of cardiac muscle (myocarditis) due, to viral infection, drugs, alcohol, etc., , SIGNS AND SYMPTOMS OF HEART FAILURE, Signs and Symptoms of Chronic Heart Failure, 1., 2., 3., 4., 5., 6., 7., 8., , Fatigue and weakness, Rapid and irregular heartbeat, Shortness of breathing, Fluid retention and weight gain, Loss of appetite, Nausea and vomiting, Cough, Chest pain, if developed by myocardial infarction., , Signs and Symptoms of Acute Heart Failure, Signs and symptoms of acute heart failure may, be same as chronic heart failure. But the signs and, symptoms appear suddenly and severely. When heart, starts to fail suddenly, the fluid accumulates in lungs, causing pulmonary edema. It results in sudden and, severe shortness of breath, cough with pink, foamy, mucus and heart palpitations. It may lead to sudden, death, if not attended immediately., TYPES OF HEART FAILURE, 1. Systolic Heart Failure, Systolic heart failure is the heart failure due to the, decreased ability of heart to contract. It may involve, right heart or left heart or both. It is caused either by, muscular weakness or valvular defect. Ventricles may, be filled with blood but cannot pump it out with sufficient, force. Ejection fraction decreases to about 20%. So the, amount of blood pumped to the body and to the lungs is, decreased. As a result, more amount of blood remains, in ventricle. Later the blood starts accumulating in, lungs or systemic veins or both. Usually the ventricle, enlarges in systolic heart failure., , 2. Diastolic Heart Failure, Diastolic heart failure is the heart failure that occurs, when the ventricles cannot relax properly due to the, stiffening of cardiac muscle. So, there is reduction in, ventricular filling and cardiac output., 3. Right Sided Heart Failure, Right sided heart failure occurs due to loss of pumping, action of the right side of the heart. Because of loss of, pumping action of right ventricle, blood accumulates in, right atrium and blood vessels. It causes edema in the, feet, ankles, legs and abdomen., 4. Left Sided Heart Failure, Left sided heart failure is due to the loss of pumping, action of the left side of the heart. It causes congestion, of lungs., COMPENSATED VERSUS, DECOMPENSATED HEART FAILURE, Chronic heart failure may be compensated or de, compensated., Compensated Heart Failure, Compensated heart failure is the heart failure with, adequate cardiac output. Heart tries to maintain cardiac, output by normal compensatory mechanisms such as, increase in heart rate, increase in force of ventricular, contraction and ventricular hypertrophy. In compensated, heart failure, the symptoms are stable and features of fluid, retention and pulmonary edema are absent. Eventually,, in most of the patients the heart can no longer meet the, demand even by compensatory mechanisms and this, condition leads to decompensated heart failure., Decompensated Heart Failure, Decompensated heart failure is the heart failure with, inadequate cardiac output. It is characterized by, deterioration and sudden and drastic worsening of, cardiac function, resulting in death.
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Cardiovascular Adjustments Chapter, during Exercise, , 117, , INTRODUCTION, TYPES OF EXERCISE, , , , DYNAMIC EXERCISE, STATIC EXERCISE, , AEROBIC AND ANAEROBIC EXERCISES, , , , , AEROBIC EXERCISE, ANAEROBIC EXERCISE, METABOLISM IN AEROBIC AND ANAEROBIC EXERCISES, , SEVERITY OF EXERCISE, , , , , MILD EXERCISE, MODERATE EXERCISE, SEVERE EXERCISE, , EFFECTS OF EXERCISE, , , , , , , , , ON BLOOD, ON BLOOD VOLUME, ON HEART RATE, ON CARDIAC OUTPUT, ON VENOUS RETURN, ON BLOOD FLOW TO SKELETAL MUSCLES, ON BLOOD PRESSURE, , INTRODUCTION, During exercise, there is an increase in metabolic needs, of body tissues, particularly the muscles., Various adjustments in the body during exercise, are aimed at:, 1. Supply of various metabolic requisites like nutrients, and oxygen to muscles and other tissues involved, in exercise, 2. Prevention of increase in body temperature., , TYPES OF EXERCISE, Exercise is generally classified into two types depending, upon the type of muscular contraction:, 1. Dynamic exercise, 2. Static exercise., , Cardiovascular changes are slightly different in, these two types of exercise., DYNAMIC EXERCISE, Dynamic exercise primarily involves the isotonic, muscular contraction. It keeps the joints and muscles, moving. Examples are swimming, bicycling, walking,, etc. Dynamic exercise involves external work, which is, the shortening of muscle fibers against load., In this type of exercise, the heart rate, force of, contraction, cardiac output and systolic blood pressure, increase. However, the diastolic blood pressure is, unaltered or decreased. It is because, during dynamic, exercise, peripheral resistance is unaltered or decreased, depending upon the severity of exercise.
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Chapter 117 t Cardiovascular Adjustments during Exercise 665, STATIC EXERCISE, Static exercise involves isometric muscular contraction, without movement of joints. Example is pushing heavy, object. Static exercise does not involve external work., During this exercise, apart from increase in heart rate,, force of contraction, cardiac output and systolic blood, pressure, the diastolic blood pressure also increases., It is because of increase in peripheral resistance during, static exercise., , AEROBIC AND ANAEROBIC EXERCISES, Based on the type of metabolism involved, exercise is, classified into two types:, 1. Aerobic exercise, 2. Anaerobic exercise., The terms aerobic and anaerobic refer to the energy, producing process during exercise. Aerobic means ‘with, air’ or ‘with oxygen’. Anaerobic means ‘without air’ or, ‘without oxygen’. Both aerobic and anaerobic exercises, are required to maintain physical fitness., , Body obtains energy by burning glycogen stored in the, muscles without oxygen hence it is called anaerobic, exercise., Burning glycogen without oxygen liberates lactic, acid. Accumulation of lactic acid leads to fatigue., Therefore, this type of exercise cannot be performed for, longer period. And a recovery period is essential before, going for another burst of anaerobic exercise. Anaerobic, exercise helps to increase the muscle strength., Examples of anaerobic exercise:, 1. Pull-ups, 2. Push-ups, 3. Weightlifting, 4. Sprinting, 5. Any other rapid burst of strenuous exercise., METABOLISM IN AEROBIC AND, ANAEROBIC EXERCISES, , Aerobic exercise involves activities with lower intensity,, which is performed for longer period. The energy is, obtained by utilizing nutrients in the presence of oxygen, and hence it is called aerobic exercise. At the beginning,, the body obtains energy by burning glycogen stored in, liver. After about 20 minutes, when stored glycogen, is exhausted the body starts burning fat. Body fat is, converted into glucose, which is utilized for energy., Aerobic exercise requires large amount of oxygen, to obtain the energy needed for prolonged exercise., Examples of aerobic exercise:, 1. Fast walking, 2. Jogging, 3. Running, 4. Bicycling, 5. Skiing, 6. Skating, 7. Hockey, 8. Soccer, 9. Tennis, 10. Badminton, 11. Swimming, 12. Rowing., , When a person starts doing some exercise like jogging,, bicycling or swimming, the muscles start utilizing, energy. In order to have quick energy during the first, few minutes, the muscles burn glycogen stored in, them. During this period, fat is not burnt. Only glycogen, is burnt and it is burnt without using oxygen. This is, called anaerobic metabolism. Lactic acid is produced, during this period. Presence of lactic acid causes some, sort of burning sensation in the muscles particularly, the muscles of arms, legs and back., Muscles burn all the muscle glycogen within 3 to 5, minutes. If the person continues the exercise beyond, this, glycogen stored in liver is converted into glucose,, which is transported to muscles through blood. Now, the body moves into aerobic metabolism. The glucose, obtained from liver is burnt in the presence of oxygen., No more lactic acid is produced. So the burning, sensation in the muscles disappears. Proper breathing, is essential during this period so that adequate oxygen, is supplied to the muscles to extract the energy from, glucose. The supply of glucose from liver in combination, with adequate availability of oxygen allows the person, to continue the exercise., Utilization of all the glycogen stored in liver is, completed by about 20 minutes. If the exercise is, continued beyond this, the body starts utilizing the fat. The, stored fat called body fat is converted into carbohydrate,, which is utilized by the muscles. This allows the person, to do the exercise for a longer period., , ANAEROBIC EXERCISE, , SEVERITY OF EXERCISE, , Anaerobic exercise involves exertion for short periods, followed by periods of rest. It uses the muscles at high, intensity and a high rate of work for a short period., , Cardiovascular and other changes in the body depend, upon the severity of exercise also. Based on severity,, the exercise is classified into three types., , AEROBIC EXERCISE
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666 Section 8 t Cardiovascular System, 1. MILD EXERCISE, Mild exercise is the very simple form of exercise like, slow walking. Little or no change occurs in cardiovascular, system during mild exercise., 2. MODERATE EXERCISE, Moderate exercise does not involve strenuous muscular, activity. So, this type of exercise can be performed for, a longer period. Exhaustion does not occur at the end, of moderate exercise. The examples of this type of, exercise are fast walking and slow running., , Increased heart rate during exercise is due to four, factors:, i. Impulses from proprioceptors, which are present, in the exercising muscles; these impulses act, through higher centers and increase the heart, rate, ii. Increased carbon dioxide tension, which acts, through medullary centers, iii. Rise in body temperature, which acts on cardiac, centers via hypothalamus, increased temperature also stimulates SA node directly, iv. Circulating catecholamines, which are secreted, in large quantities during exercise., , 3. SEVERE EXERCISE, Severe exercise involves strenuous muscular activity., The severity can be maintained only for short duration., Fast running for a distance of 100 or 400 meters is, the best example of this type of exercise. Complete, exhaustion occurs at the end of severe exercise., , EFFECTS OF EXERCISE ON, CARDIOVASCULAR SYSTEM, 1. ON BLOOD, Mild hypoxia developed during exercise stimulates the, juxtaglomerular apparatus to secrete erythropoietin. It, stimulates the bone marrow and causes release of red, blood cells. Increased carbon dioxide content in blood, decreases the pH of blood., 2. ON BLOOD VOLUME, More heat is produced during exercise and the thermoregulatory system is activated. This in turn, causes, secretion of large amount of sweat leading to:, i. Fluid loss, ii. Reduced blood volume, iii. Hemoconcentration, iv. Sometimes, severe exercise leads to even, dehydration., 3. ON HEART RATE, Heart rate increases during exercise. Even the thought, of exercise or preparation for exercise increases the, heart rate. It is because of impulses from cerebral cortex, to medullary centers, which reduces vagal tone., In moderate exercise, the heart rate increases, to 180 beats/minute. In severe muscular exercise, it, reaches 240 to 260 beats/minute. Increased heart rate, during exercise is mainly because of vagal withdrawal., Increase in sympathetic tone also plays some role., , 4. ON CARDIAC OUTPUT, Cardiac output increases up to 20 L/minute in moderate, exercise and up to 35 L/minute during severe exercise., Increase in cardiac output is directly proportional to the, increase in the amount of oxygen consumed during, exercise., During exercise, the cardiac output increases, because of increase in heart rate and stroke volume., Heart rate increases because of vagal withdrawal., Stroke volume increases due to increased force of, contraction. Because of vagal withdrawal, sympathetic, activity increases leading to increase in rate and force, of contraction., 5. ON VENOUS RETURN, Venous return increases remarkably during exercise, because of muscle pump, respiratory pump and, splanchnic vasoconstriction (Chapter 98)., 6. ON BLOOD FLOW TO SKELETAL MUSCLES, There is a great increase in the amount of blood, flowing to skeletal muscles during exercise. In resting, condition, the blood supply to the skeletal muscles is, 3 to 4 mL/100 g of the muscle/minute. It increases up, to 60 to 80 mL in moderate exercise and up to 90 to, 120 mL in severe exercise., During the muscular activity, stoppage of blood, flow occurs when the muscles contract. It is because of, compression of blood vessels during contraction. And in, between the contractions, the blood flow increases., Sometimes the blood supply to muscles starts, increasing even during the preparation for exercise. It, is due to the sympathetic activity. Sympathetic nerves, cause vasodilatation in muscles. The sympathetic nerve, fibers causing vasodilatation in skeletal muscle are, called sympathetic cholinergic fibers since these fibers, secrete acetylcholine instead of noradrenaline.
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Chapter 117 t Cardiovascular Adjustments during Exercise 667, Several other factors also are responsible for the, increase in blood flow to muscles during exercise., All such factors increase the amount of blood flow to, muscles by means of dilatation of blood vessels of the, muscles. Such factors are:, i. Hypercapnea, ii. Hypoxia, iii. Potassium ions, iv. Metabolites like lactic acid, v. Rise in temperature, vi. Adrenaline secreted from adrenal medulla, vii. Increased sympathetic cholinergic activity., 7. ON BLOOD PRESSURE, During moderate isotonic exercise, the systolic, pressure is increased. It is due to increase in heart rate, and stroke volume. Diastolic pressure is not altered, because peripheral resistance is not affected during, moderate isotonic exercise., , In severe exercise involving isotonic muscular, contraction, the systolic pressure enormously increases, but the diastolic pressure decreases. Decrease in, diastolic pressure is because of the decrease in peripheral resistance. Decrease in peripheral resistance is, due to vasodilatation caused by metabolites., During exercise involving isometric contraction,, the peripheral resistance increases. So, the diastolic, pressure also increases along with systolic pressure., Blood Pressure after Exercise, Large quantities of metabolic end products are produced, during exercise. These substances accumulate in the, tissues, particularly the skeletal muscle. Metabolic end, products cause vasodilatation. So, the blood pressure, falls slightly below the resting level after the exercise., However, the pressure returns to resting level quickly, as soon as the metabolic end products are removed, from muscles.
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668 Questions in Cardiovascular System, , QUESTIONS IN CARDIOVASCULAR SYSTEM, , LONG QUESTIONS, 1. Define cardiac cycle. Describe various events of, cardiac cycle with pressure and volume changes., 2. Define electrocardiogram. Describe the waves,, segments and intervals of normal ECG. Add a, note on ECG leads., 3. Give the definitions, normal values and variations, of cardiac output. Explain the factors regulating, cardiac output., 4. What is cardiac output? Enumerate the various, methods to measure cardiac output and explain, the measurement of cardiac output by applying, Fick principle., 5. Describe the innervation of heart and the regulation of heart rate., 6. Define arterial blood pressure. Describe the nerv, ous regulation of arterial blood pressure., 7. Describe renal mechanism of (long term) regulation of arterial blood pressure., 8. What is the normal blood flow through coronary, circulation? Explain the phasic changes, measurement and regulation of coronary blood blow., 9. Give an account of cerebral circulation., 10. Define hemorrhage. Explain various effects of, hemorrhage., 11. Describe the cardiovascular and respiratory, changes during exercise., , SHORT QUESTIONS, 1., 2., 3., 4., 5., 6., 7., 8., 9., 10., 11., 12., 13., 14., 15., 16., 17., 18., , Action potential in cardiac muscle., Pacemaker., Pacemaker potential., Conductive system in heart., Allornone law., Refractory period in cardiac muscle., Isometric contraction period., Atrial pressure changes during cardiac cycle., Ventricular pressure changes during cardiac cycle., Ventricular volume changes during cardiac cycle., Ejection fraction., Heart sounds., First and second heart sounds., Phonocardiogram., Cardiac murmurs., Waves of normal ECG., ECG leads., Mean QRS vector., , 19., 20., 21., 22., 23., 24., 25., 26., 27., 28., 29., 30., 31., 32., 33., 34., 35., 36., 37., 38., 39., 40., 41., 42., 43., 44., 45., 46., 47., 48., 49., 50., 51., 52., 53., 54., 55., 56., 57., 58., 59., 60., 61., 62., 63., 64., 65., 66., , Vectorcardiogram., Sinus arrhythmia., Heart block., Extrasystole., Stokes-Adams syndrome., Abnormal pacemaker., Current of injury., Effect of electrolyte changes on heart., Venous return., Peripheral resistance., Fick principle., Cardiac catheterization., Cardiac function curves., Cardiac centers., Nerve supply to heart., Vagal tone., Marey reflex., Sinoaortic mechanism., Buffer nerves., Baroreceptors., Chemoreceptors., Bainbridge reflex., Streamline and turbulent flow of blood., Windkessel effect., Mean volume of blood flow., Velocity of blood flow., Circulation time., Autoregulation., Determinants of arterial blood pressure., Vasomotor center., Vasomotor tone., Nerve supply to blood vessels., Renal regulation of blood pressure., Vasoconstrictor substances., Vasodilator substances., Renin-angiotensin mechanism., Hypertension., Venous pressure., Capillary pressure., Arterial pulse., Phlebogram., Phasic changes in coronary blood flow., Regulation of coronary circulation., Coronary occlusion., Myocardial infarction., Angina pectoris., Physiological shunt in heart., Measurement of cerebral blood flow.
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Questions in Cardiovascular System 669, 67., 68., 69., 70., 71., 72., 73., 74., , Regulation of cerebral blood flow., Cushing reflex., Stroke or cardiovascular accident., Capillary circulation (microcirculation)., Shunt in capillaries., Cutaneous circulation., Vascular responses of skin., Lewis triple response., , 75., 76., 77., 78., 79., 80., 81., 82., , Fetal circulation., Neonatal circulation., Hemorrhage., Manifestations of circulatory shock., Syncope or fainting., Vasovagal syncope., Cardiovascular changes in moderate exercise., Effect of exercise on blood pressure.
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Section, , 9, , 118., 119., 120., 121., 122., 123., 124., 125., 126., 127., 128., 129., 130., 131., 132., , Respiratory System, and Environmental, Physiology, , Physiological Anatomy of Respiratory Tract ............................................ 673, Pulmonary Circulation ............................................................................. 678, Mechanics of Respiration ........................................................................ 682, Pulmonary Function Tests ....................................................................... 690, Ventilation ................................................................................................ 700, Inspired Air, Alveolar Air and Expired Air ................................................. 703, Exchange of Respiratory Gases ............................................................. 705, Transport of Respiratory Gases ............................................................. 711, Regulation of Respiration ........................................................................ 716, Disturbances of Respiration .................................................................... 723, High Altitude and Space Physiology ....................................................... 737, Deep Sea Physiology .............................................................................. 743, Effects of Exposure to Cold and Heat ..................................................... 746, Artificial Respiration ................................................................................ 749, Effects of Exercise on Respiration .......................................................... 751
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Physiological Anatomy of, Respiratory Tract, , Chapter, , 118, , INTRODUCTION, , , , TYPES OF RESPIRATION, PHASES OF RESPIRATION, , FUNCTIONAL ANATOMY OF RESPIRATORY TRACT, RESPIRATORY UNIT, , , , STRUCTURE OF RESPIRATORY UNIT, RESPIRATORY MEMBRANE, , NON-RESPIRATORY FUNCTIONS OF RESPIRATORY TRACT, , , , , , , , , , , , OLFACTION, VOCALIZATION, PREVENTION OF DUST PARTICLES, DEFENSE MECHANISM, MAINTENANCE OF WATER BALANCE, REGULATION OF BODY TEMPERATURE, REGULATION OF ACID-BASE BALANCE, ANTICOAGULANT FUNCTION, SECRETION OF ANGIOTENSIN-CONVERTING ENZYME, SYNTHESIS OF HORMONAL SUBSTANCES, , RESPIRATORY PROTECTIVE REFLEXES, , , , , COUGH REFLEX, SNEEZING REFLEX, SWALLOWING REFLEX, , INTRODUCTION, Respiration is the process by which oxygen is taken in, and carbon dioxide is given out. The first breath takes, place only after birth. Fetal lungs are non-functional., So, during intrauterine life the exchange of gases, between fetal blood and mother’s blood occurs through, placenta., After the first breath, the respiratory process con, tinues throughout the life. Permanent stoppage of, respiration occurs only at death., , Late childhood : 15 to 25/minute, Adult, : 12 to 16/minute., TYPES OF RESPIRATION, Respiration is classified into two types:, 1. External respiration that involves exchange of, respiratory gases, i.e. oxygen and carbon dioxide, between lungs and blood, 2. Internal respiration, which involves exchange of, gases between blood and tissues., PHASES OF RESPIRATION, , Normal Respiratory Rate at Different Age, Newborn, : 30 to 60/minute, Early childhood : 20 to 40/minute, , Respiration occurs in two phases:, 1. Inspiration during which air enters the lungs from, atmosphere
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674 Section 9 t Respiratory System and Environmental Physiology, 2. Expiration during which air leaves the lungs., During normal breathing, inspiration is an active, process and expiration is a passive process., , FUNCTIONAL ANATOMY OF, RESPIRATORY TRACT, Respiratory tract is the anatomical structure through, which air moves in and out. It includes nose, pharynx,, larynx, trachea, bronchi and lungs (Fig. 118.1)., , Functions of intrapleural fluid, 1. It functions as the lubricant to prevent friction, between two layers of pleura, 2. It is involved in creating the negative pressure called, intrapleural pressure within intrapleural space., Pleural Cavity in Abnormal Conditions, In some pathological conditions, the pleural cavity, expands with accumulation of air (pneumothorax), water, (hydrothorax), blood (hemothorax) or pus (pyothorax)., , Pleura, Each lung is enclosed by a bilayered serous membrane, called pleura or pleural sac. Pleura has two layers, namely inner visceral and outer parietal layers. Visceral, layer is attached firmly to the surface of the lungs., At hilum, it is continuous with parietal layer, which is, attached to the wall of thoracic cavity., Intrapleural Space or Pleural Cavity, Intrapleural space or pleural cavity is the narrow space, in between the two layers of pleura., Intrapleural Fluid, Intrapleural space contains a thin film of serous fluid, called intrapleural fluid, which is secreted by the visceral, layer of the pleura., , Tracheobronchial Tree, Trachea and bronchi are together called tracheo, bronchial tree. It forms a part of air passage., Components of tracheobronchial tree, 1. Trachea bifurcates into two main or primary bronchi, called right and left bronchi, 2. Each primary bronchus enters the lungs and divides, into secondary bronchi, 3. Secondary bronchi divide into tertiary bronchi. In, right lung, there are 10 tertiary bronchi and in left, lung, there are eight tertiary bronchi, 4. Tertiary bronchi divide several times with reduction, in length and diameter into many generations of, bronchioles, , 5. When the diameter of bronchiole becomes 1 mm or, less, it is called terminal bronchiole, 6. Terminal bronchiole continues or divides into, respiratory bronchioles, which have a diameter of, 0.5 mm., Upper and Lower Respiratory Tracts, Generally, respiratory tract is divided into two parts:, 1. Upper respiratory tract that includes all the, structures from nose up to vocal cords; vocal cords, are the folds of mucous membrane within larynx, that vibrates to produce the voice, 2. Lower respiratory tract, which includes trachea,, bronchi and lungs., , RESPIRATORY UNIT, Parenchyma of lungs is formed by respiratory unit, that forms the terminal portion of respiratory tract., Respiratory unit is defined as the structural and, functional unit of lung. Exchange of gases occurs only, in this part of the respiratory tract., STRUCTURE OF RESPIRATORY UNIT, FIGURE 118.1: Respiratory tract, , Respiratory unit starts from the respiratory bronchioles, (Fig. 118.2). Each respiratory bronchiole divides into
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Chapter 118 t Physiological Anatomy of Respiratory Tract 675, alveolar ducts. Each alveolar duct enters an enlarged, structure called the alveolar sac. Space inside the, alveolar sac is called antrum. Alveolar sac consists of a, cluster of alveoli. Few alveoli are present in the wall of, , alveolar duct also., Thus, respiratory unit includes:, 1. Respiratory bronchioles, 2. Alveolar ducts, 3. Alveolar sacs, 4. Antrum, 5. Alveoli., Each alveolus is like a pouch with the diameter of, about 0.2 to 0.5 mm. It is lined by epithelial cells., Alveolar Cells or Pneumocytes, Alveolar epithelium consists of alveolar cells or pneumo, cytes, which are of two types namely type I alveolar, cells and type II alveolar cells., , RESPIRATORY MEMBRANE, Respiratory membrane is the membranous structure, through which the exchange of gases occurs., Respiratory membrane separates air in the alveoli, from the blood in capillary. It is formed by the alveolar, membrane and capillary membrane. Respiratory mem, brane has a surface area of 70 square meter and thick, ness of 0.5 micron. Structure of respiratory membrane, is explained in Chapter 124 (See Fig. 124.1)., , NON-RESPIRATORY FUNCTIONS, OF RESPIRATORY TRACT, Besides primary function of gaseous exchange, the, respiratory tract is involved in several nonrespiratory, functions of the body. Particularly, the lungs function as, a defense barrier and metabolic organs, which synthe, size some important compounds. Nonrespiratory, functions of the respiratory tract are:, , Type I alveolar cells, Type I alveolar cells are the squamous epithelial cells, forming about 95% of the total number of cells. These, cells form the site of gaseous exchange between the, alveolus and blood., Type II alveolar cells, Type II alveolar cells are cuboidal in nature and form, about 5% of alveolar cells. These cells are also called, granular pneumocytes. Type II alveolar cells secrete, alveolar fluid and surfactant., , 1. OLFACTION, Olfactory receptors present in the mucous membrane, of nostril are responsible for olfactory sensation., 2. VOCALIZATION, Along with other structures, larynx forms the speech, apparatus. However, larynx alone plays major role in, the process of vocalization. Therefore, it is called sound, box., 3. PREVENTION OF DUST PARTICLES, Dust particles, which enter the nostrils from air, are, prevented from reaching the lungs by filtration action of, the hairs in nasal mucous membrane. Small particles,, which escape the hairs, are held by the mucus secreted, by nasal mucous membrane. Those dust particles,, which escape nasal hairs and nasal mucous membrane,, are removed by the phagocytic action of macrophages, in the alveoli., Particles, which escape the protective mechanisms, in nose and alveoli are thrown out by cough reflex and, sneezing reflex (Chapter 126)., 4. DEFENSE MECHANISM, , FIGURE 118.2: Respiratory unit, , Lungs play important role in the immunological, defense system of the body. Defense functions of, the lungs are performed by their own defenses and, by the presence of various types of cells in mucous, membrane lining the alveoli of lungs. These cells are, leukocytes, macrophages, mast cells, natural killer, cells and dendritic cells.
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676 Section 9 t Respiratory System and Environmental Physiology, i. Lung’s Own Defenses, , vi. Defense through Dendritic Cells, , Epithelial cells lining the air passage secrete some in, nate immune factors called defensins and cathelicidins., These substances are the antimicrobial peptides, which, play an important role in lung’s natural defenses. Refer, Chapter 17 for detail., , Dendritic cells in the lungs play important role in, immunity. Along with macrophages, these cells function, as antigen presenting cells., , ii. Defense through Leukocytes, Leukocytes, particularly the neutrophils and lympho, cytes present in the alveoli of lungs provide defense, mechanism against bacteria and virus. Neutrophils kill, the bacteria by phagocytosis. Lymphocytes develop, immunity against bacteria., iii. Defense through Macrophages, Macrophages engulf the dust particles and the, pathogens, which enter the alveoli and thereby act as, scavengers in lungs. Macrophages are also involved in, the development of immunity by functioning as antigen, presenting cells. When foreign organisms invade the, body, the macrophages and other antigen presenting, cells kill them. Later, the antigen from the organisms is, digested into polypeptides. Polypeptide products are, presented to T lymphocytes and B lymphocytes by the, macrophages., Macrophages secrete interleukins, tumor necrosis, factors (TNF) and chemokines (Chapter 24). Interleukins, and TNF activate the general immune system of the, body (Chapter 17). Chemokines attract the white blood, cells towards the site of any inflammation., iv. Defense through Mast Cell, Mast cell is a large cell resembling the basophil. Mast, cell produces the hypersensitivity reactions like allergy, and anaphylaxis (Chapter 17). It secretes heparin,, histamine, serotonin and hydrolytic enzymes., v. Defense through Natural Killer Cell, Natural killer (NK) cell is a large granular cell,, considered as the third type of lymphocyte. Usually NK, cell is present in lungs and other lymphoid organs. Its, granules contain hydrolytic enzymes, which destroy the, microorganisms., NK cell is said to be the first line of defense in, specific immunity particularly against viruses., It destroys the viruses and viral infected or, damaged cells, which may form the tumors. It also, destroys the malignant cells and prevents development, of cancerous tumors. NK cells secrete interferons and, the tumor necrosis factors (Chapter 17)., , 5. MAINTENANCE OF WATER BALANCE, Respiratory tract plays a role in water loss mechanism., During expiration, water evaporates through the, expired air and some amount of body water is lost by, this process., 6. REGULATION OF BODY TEMPERATURE, During expiration, along with water, heat is also lost, from the body. Thus, respiratory tract plays a role in, heat loss mechanism., 7. REGULATION OF ACID-BASE BALANCE, Lungs play a role in maintenance of acidbase balance, of the body by regulating the carbon dioxide content, in blood. Carbon dioxide is produced during various, metabolic reactions in the tissues of the body. When it, enters the blood, carbon dioxide combines with water, to form carbonic acid. Since carbonic acid is unstable,, it splits into hydrogen and bicarbonate ions., CO2 + H2O → H2CO3 → H+ + HCO3–, Entire reaction is reversed in lungs when carbon, dioxide is removed from blood into the alveoli of lungs, (Chapter 125)., H+ + HCO3– → H2CO3 → CO2 + H2O, As carbon dioxide is a volatile gas, it is practically, blown out by ventilation., When metabolic activities are accelerated, more, amount of carbon dioxide is produced in the tissues., Concentration of hydrogen ion is also increased., This leads to reduction in pH. Increased hydrogen, ion concentration causes increased pulmonary venti, lation (hyperventilation) by acting through various, mechanisms like chemoreceptors in aortic and carotid, bodies and in medulla of the brain (Chapter 126). Due to, hyperventilation, excess of carbon dioxide is removed, from body fluids and the pH is brought back to normal., 8. ANTICOAGULANT FUNCTION, Mast cells in lungs secrete heparin. Heparin is an, anticoagulant and it prevents the intravascular clotting., , 9. SECRETION OF ANGIOTENSINCONVERTING ENZYME, Endothelial cells of the pulmonary capillaries secrete, the angiotensinconverting enzyme (ACE). It converts
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Chapter 118 t Physiological Anatomy of Respiratory Tract 677, the angiotensin I into active angiotensin II, which plays, an important role in the regulation of ECF volume and, blood pressure (Chapter 50)., 10. SYNTHESIS OF HORMONAL SUBSTANCES, Lung tissues are also known to synthesize the hormonal, substances, prostaglandins, acetylcholine and serotonin,, which have many physiological actions in the body, including regulation of blood pressure (Chapter 73)., , RESPIRATORY PROTECTIVE REFLEXES, Respiratory protective reflexes are the reflexes that, protect lungs and air passage from foreign particles., Respiratory process is modified by these reflexes in, order to eliminate the foreign particles or to prevent, the entry of these particles into the respiratory tract., Following are the respiratory protective reflexes:, COUGH REFLEX, Cough is a modified respiratory process characterized, by forced expiration. It is a protective reflex and it is, caused by irritation of respiratory tract and some other, areas such as external auditory canal (see below)., Causes, Cough is produced mainly by irritant agents. It is, also produced by several disorders such as cardiac, disorders (congestive heart failure), pulmonary, disorders (chronic obstructive pulmonary disease –, COPD) and tumor in thorax, which may exert pressure, on larynx, trachea, bronchi or lungs., Mechanism, Cough begins with deep inspiration followed by forced, expiration with closed glottis. This increases the intra, pleural pressure above 100 mm Hg. Then, glottis, opens suddenly with explosive outflow of air at a high, velocity. Velocity of the airflow may reach 960 km/hour., It causes expulsion of irritant substances out of the, respiratory tract., Reflex Pathway, Receptors that initiate the cough are situated in, several locations such as nose, paranasal sinuses,, larynx, pharynx, trachea, bronchi, pleura, diaphragm,, pericardium, stomach, external auditory canal and, tympanic membrane., , Afferent nerve fibers pass via vagus, trigeminal,, glossopharyngeal and phrenic nerves. The center for, cough reflex is in the medulla oblongata., Efferent nerve fibers arising from the medullary, center pass through the vagus, phrenic and spinal, motor nerves. These nerve fibers activate the primary, and accessory respiratory muscles., SNEEZING REFLEX, Sneezing is also a modified respiratory process, characterized by forced expiration. It is a protective reflex, caused by irritation of nasal mucous membrane., Causes, Irritation of the nasal mucous membrane occurs be, cause of dust particles, debris, mechanical obstruction, of the airway and excess fluid accumulation in the, nasal passages., Mechanism, Sneezing starts with deep inspiration, followed by, forceful expiratory effort with opened glottis resulting in, expulsion of irritant agents out of respiratory tract., Reflex Pathway, Sneezing is initiated by the irritation of nasal mucous, membrane, the olfactory receptors and trigeminal nerve, endings present in the nasal mucosa., Afferent nerve fibers pass through the trigeminal, and olfactory nerves. Sneezing center is in medulla, oblongata. It is located diffusely in spinal nucleus of, trigeminal nerve, nucleus solitarius and the reticular, formation of medulla., Efferent nerve fibers from the medullary center, pass via trigeminal, facial, glossopharyngeal, vagus, and intercostal nerves. These nerve fibers activate the, pharyngeal, tracheal and respiratory muscles., SWALLOWING (DEGLUTITION) REFLEX, Swallowing reflex is a respiratory protective reflex, that prevents entrance of food particles into the air, passage during swallowing., While swallowing of the food, the respiration is, arrested for a while. Temporary arrest of respiration is, called apnea. Arrest of breathing during swallowing is, called swallowing apnea or deglutition apnea. It takes, place during pharyngeal stage, i.e. second stage of, deglutition and prevents entry of food particles into the, respiratory tract. Refer Chapter 43 for details.
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Pulmonary Circulation, , Chapter, , 119, , PULMONARY BLOOD VESSELS, , , , , , , , , , , PULMONARY ARTERY, BRONCHIAL ARTERY, PHYSIOLOGICAL SHUNT, , CHARACTERISTIC FEATURES OF PULMONARY BLOOD VESSELS, PULMONARY BLOOD FLOW, PULMONARY BLOOD PRESSURE, MEASUREMENT OF PULMONARY BLOOD FLOW, REGULATION OF PULMONARY BLOOD FLOW, , , , , , , CARDIAC OUTPUT, VASCULAR RESISTANCE, NERVOUS FACTORS, CHEMICAL FACTORS, GRAVITY AND HYDROSTATIC PRESSURE, , PULMONARY BLOOD VESSELS, Pulmonary blood vessels include pulmonary artery,, which carries deoxygenated blood to alveoli of lungs, and bronchial artery, which supply oxygenated blood, to other structures of lungs (see below)., PULMONARY ARTERY, Pulmonary artery supplies deoxygenated blood pumped, from right ventricle to alveoli of lungs (pulmonary, circulation). After leaving the right ventricle, this artery, divides into right and left branches. Each branch enters, the corresponding lung along with primary bronchus., After entering the lung, branch of the pulmonary artery, divides into small vessels and finally forms the capillary, plexus that is in intimate relationship to alveoli. Capillary, plexus is solely concerned with alveolar gas exchange., Oxygenated blood from the alveoli is carried to left, atrium by one pulmonary vein from each side., BRONCHIAL ARTERY, Bronchial artery arises from descending thoracic aorta., It supplies arterial blood to bronchi, connective tissue, , and other structures of lung stroma, visceral pleura, and pulmonary lymph nodes. Venous blood from these, structures is drained by two bronchial veins from each, side. Bronchial veins from right side drain into azygos, vein and the left bronchial veins drain into superior, hemiazygos or left superior intercostal veins. However,, the blood from distal portion of bronchial circulation is, drained directly into the tributaries of pulmonary veins., PHYSIOLOGICAL SHUNT, Definition, Physiological shunt is defined as a diversion through, which the venous blood is mixed with arterial blood., Components, Physiological shunt has two components:, 1. Flow of deoxygenated blood from bronchial circula, tion into pulmonary veins without being oxygenated, makes up part of normal physiological shunt, 2. Flow of deoxygenated blood from thebesian veins, into cardiac chambers directly (Chapter 108).
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Chapter 119 t Pulmonary Circulation 679, Venous Admixture and Wasted Blood, Physiological shunt results in venous admixture., Venous admixture refers to mixing of deoxygenated, blood with oxygenated blood. Fraction of venous blood,, which is not fully oxygenated is generally considered, as wasted blood., Normal Shunt Level and its Variations, Normal physiological shunt of venous blood to the left, side of heart is 1% to 2% of cardiac output. In normal, persons, it may increase up to 5% of cardiac output,, which may be due to mismatching of ventilationperfusion ratio within physiological limits., Pathological increase in the shunt occurs in several, conditions such as acute pulmonary infections and, bronchiectasis (permanent dilatation of bronchi due, to chronic pulmonary infections and inflammatory, processes)., Physiological Shunt Vs Physiological, Dead Space, Physiological shunt is analogous to physiological dead, space (Chapter 122). Physiological shunt includes, wasted blood and physiological dead space includes, wasted air. Both wasted blood and wasted air exist on, either side of alveolar membrane and both affect the, ventilation-perfusion ratio (Chapter 122)., , CHARACTERISTIC FEATURES OF, PULMONARY BLOOD VESSELS, Following are the characteristic features of pulmonary, blood vessels:, 1. Pulmonary artery has a thin wall. Its thickness is, only about one third of thickness of the systemic, aortic wall. Wall of other pulmonary blood vessels is, also thin., 2. Pulmonary blood vessels are highly elastic and, more distensible, 3. Smooth muscle coat is not well developed in the, pulmonary blood vessels, 4. True arterioles have less smooth muscle fibers, 5. Pulmonary capillaries are larger than systemic, capillaries. Pulmonary capillaries are also dense, and have multiple anastomosis, so, each alveolus, occupies a capillary basket., 6. Vascular resistance in pulmonary circulation is very, less; it is only one tenth of systemic circulation, 7. Pulmonary vascular system is a low pressure, system. Pulmonary arterial pressure and pulmonary capillary pressure are very low (see below)., , 8. Pulmonary artery carries deoxygenated blood, from heart to lungs and pulmonary veins carry, oxygenated blood from lungs to heart, 9. Physiological shunt is present., , PULMONARY BLOOD FLOW, Lungs receive the whole amount of blood that is pumped, out from right ventricle. Output of blood per minute is, same in both right and left ventricle. It is about 5 liter., Thus, the lungs accommodate amount of blood,, which is equal to amount of blood accommodated by all, other parts of the body., , PULMONARY BLOOD PRESSURE, Pulmonary blood vessels are more distensible than, systemic blood vessels. So the blood pressure is less, in pulmonary blood vessels. Thus, the entire pulmonary, vascular system is a low pressure bed., Pulmonary Arterial Pressure, Systolic pressure, : 25 mm Hg, Diastolic pressure, : 10 mm Hg, Mean arterial pressure : 15 mm Hg., Pulmonary Capillary Pressure, Pulmonary capillary pressure is about 7 mm Hg. This, pressure is sufficient for exchange of gases between, alveoli and blood., , MEASUREMENT OF PULMONARY, BLOOD FLOW, Pulmonary blood flow is measured by applying Fick, principle. Details are given in Chapter 98., , REGULATION OF PULMONARY, BLOOD FLOW, Pulmonary blood flow is regulated by the following, factors:, 1. Cardiac output, 2. Vascular resistance, 3. Nervous factors, 4. Chemical factors, 5. Gravity and hydrostatic pressure., 1. CARDIAC OUTPUT, Pulmonary blood flow is directly proportional to, cardiac output. So, any factor that alters the cardiac, output, also affects pulmonary blood flow.
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680 Section 9 t Respiratory System and Environmental Physiology, Cardiac output is in turn regulated by four factors:, i. Venous return, ii. Force of contraction, iii. Rate of contraction, iv. Peripheral resistance., Refer Chapter 98 for details of factors affecting, cardiac output., 2. VASCULAR RESISTANCE, Pulmonary blood flow is inversely proportional to the, pulmonary vascular resistance. Pulmonary vascular, resistance is low compared to systemic vascular, resistance. Pulmonary vascular resistance is altered, in different phases of respiration. During inspiration,, pulmonary blood vessels are distended because, of decreased intrathoracic pressure. This causes, decrease in vascular resistance resulting in increased, pulmonary blood flow (Fig. 119.1). During expiration,, the pulmonary vascular resistance increases resulting, in decreased blood flow., During the conditions like exercise, the vascular, resistance decreases and blood flow increases. It, is influenced by the exercise-induced hypoxia and, hypercapnea., 3. NERVOUS FACTORS, Stimulation of sympathetic nerves under experimental, conditions increases the pulmonary vascular resistance by vasoconstriction and the stimulation of parasympathetic, i.e. vagus nerve decreases the vascular, resistance by vasodilatation., However, under physiological conditions, it is, doubtful whether autonomic nerves play any role in, regulating the blood flow to lungs., , FIGURE 119.1: Schematic diagram showing increase in, pulmonary blood flow during inspiration, , 4. CHEMICAL FACTORS, Excess of carbon dioxide or lack of oxygen causes, vasoconstriction. The cause for pulmonary vasoconstriction by hypoxia is not known. But it has some, significance. If some part of lungs is affected by, hypoxia, there is constriction of capillaries in that area., Thus, blood is directed to the alveoli of neighboring, area where gaseous exchange occurs., 5. GRAVITY AND HYDROSTATIC PRESSURE, Normally in standing position, blood pressure in lower, extremity of the body is very high and in upper parts, above the level of heart, the pressure is low. This is, because of the effect of gravitational force., A similar condition is observed to some extent in, lungs also. Pulmonary vascular pressure varies in, different parts of the lungs:, i. Apical Portion – Zone 1, Normally, in the apical portion of lungs, pulmonary, capillary pressure is almost same as alveolar pressure., So, the pulmonary arterial pressure is just sufficient, for flow of blood into alveolar capillaries. However, if, pulmonary arterial pressure decreases or if alveolar, pressure increases, the capillaries are collapsed. This, prevents flow of blood to alveoli. So, this zone of lung is, called area of zero blood flow (Fig. 119.2)., Under these conditions, there is no gaseous exchange in this zone of lungs. So, it is considered as the, part of physiological dead space, which is ventilated, but not perfused. And, the ventilation-perfusion ratio, increases. It may lead to growth of bacteria, particularly, tubercle bacilli making this part of lungs susceptible, for tuberculosis., , FIGURE 119.2: Pattern of blood flow in various, areas of lungs
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Chapter 119 t Pulmonary Circulation 681, ii. Midportion – Zone 2, , iii. Lower Portion – Zone 3, , In the midportion of lungs, the pressure in alveoli is, less than pulmonary systolic pressure and more than, the pulmonary diastolic pressure. Because of this, the, blood flow to the alveoli increases during systole and, decreases during diastole. So, this zone of the lung is, called area of intermittent flow. Ventilation-perfusion, ratio is normal., , In the lower portion of lungs, the pulmonary arterial, pressure is high and it is more than alveolar pressure, both during systole and diastole. So the blood flows, continuously. Hence, this part of lungs is called area, of continuous blood flow. Ventilation-perfusion ratio, decreases because of increased blood flow.
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Mechanics of Respiration, , Chapter, , 120, , RESPIRATORY MOVEMENTS, , , , , , INTRODUCTION, MUSCLES OF RESPIRATION, MOVEMENTS OF THORACIC CAGE, MOVEMENTS OF LUNGS, , RESPIRATORY PRESSURES, , , , INTRAPLEURAL PRESSURE, INTRA-ALVEOLAR PRESSURE, , COMPLIANCE, , , , , , , DEFINITION, NORMAL VALUES, TYPES, MEASUREMENT, APPLIED PHYSIOLOGY, , WORK OF BREATHING, , , , WORK DONE BY RESPIRATORY MUSCLES, UTILIZATION OF ENERGY, , RESPIRATORY MOVEMENTS, INTRODUCTION, Respiration occurs in two phases namely inspiration, and expiration., During inspiration, thoracic cage enlarges and, lungs expand so that air enters the lungs easily. During, expiration, the thoracic cage and lungs decrease in size, and attain the preinspiratory position so that air leaves, the lungs easily., During normal quiet breathing, inspiration is the, active process and expiration is the passive process., , However, respiratory muscles are generally classi, fied into two types:, 1. Primary or major respiratory muscles, which are, responsible for change in size of thoracic cage, during normal quiet breathing, 2. Accessory respiratory muscles that help primary, respiratory muscles during forced respiration., Inspiratory Muscles, Muscles involved in inspiratory movements are known, as inspiratory muscles., Primary inspiratory muscles, , MUSCLES OF RESPIRATION, Respiratory muscles are of two types:, 1. Inspiratory muscles, 2. Expiratory muscles., , Primary inspiratory muscles are the diaphragm, which, is supplied by phrenic nerve (C3 to C5) and external, intercostal muscles, supplied by intercostal nerves, (T1 to T11).
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Chapter 120 t Mechanics of Respiration 683, Accessory inspiratory muscles, , Pump handle movement, , Sternocleidomastoid, scalene, anterior serrati, eleva, tors of scapulae and pectorals are the accessory, inspiratory muscles., Expiratory Muscles, , Contraction of external intercostal muscles causes, elevation of these ribs and upward and forward move, ment of sternum. This movement is called pump handle, movement. It increases anteroposterior diameter of, the thoracic cage., , Primary expiratory muscles, , Bucket handle movement, , Primary expiratory muscles are the internal intercostal, muscles, which are innervated by intercostal nerves., , Simultaneously, the central portions of these ribs (arch, es of ribs) move upwards and outwards to a more hori, zontal position. This movement is called bucket handle, movement and it increases the transverse diameter of, thoracic cage., , Accessory expiratory muscles, Accessory expiratory muscles are the abdominal, muscles., , 3. Lower Costal Series, MOVEMENTS OF THORACIC CAGE, Inspiration causes enlargement of thoracic cage. Thor, acic cage enlarges because of increase in all diameters,, viz. anteroposterior, transverse and vertical diameters., Anteroposterior and transverse diameters of thoracic, cage are increased by the elevation of ribs. Vertical, diameter is increased by the descent of diaphragm., In general, change in the size of thoracic cavity, occurs because of the movements of four units of, structures:, 1. Thoracic lid, 2. Upper costal series, 3. Lower costal series, 4. Diaphragm., , Lower costal series includes seventh to tenth pair of, ribs. Movement of lower costal series increases the, transverse diameter of thoracic cage by bucket handle, movement., Bucket handle movement, Lower costal series of ribs also show bucket handle, movement by swinging outward and upward. This, movement increases the transverse diameter of the, thoracic cage., Eleventh and twelfth pairs of ribs are the floating, ribs. These ribs are not involved in changing the size of, thoracic cage., 4. Diaphragm, , 1. Thoracic Lid, Thoracic lid is formed by manubrium sterni and the first, pair of ribs. It is also called thoracic operculum., Movement of thoracic lid increases the anteroposterior diameter of thoracic cage. Due to the con, traction of scalene muscles, the first ribs move upwards, to a more horizontal position. This increases the antero, posterior diameter of upper thoracic cage., , Movement of diaphragm increases the vertical dia, meter of thoracic cage. Normally, before inspiration, the diaphragm is dome shaped with convexity facing, upwards. During inspiration, due to the contraction,, muscle fibers are shortened. But the central tendinous, portion is drawn downwards so the diaphragm is flat, tened. Flattening of diaphragm increases the vertical, diameter of the thoracic cage., , 2. Upper Costal Series, , MOVEMENTS OF LUNGS, , Upper costal series is constituted by second to sixth, pair of ribs. Movement of upper costal series increases, the anteroposterior and transverse diameter of the, thoracic cage., Movement of upper costal series is of two types:, i. Pump handle movement, ii. Bucket handle movement., , During inspiration, due to the enlargement of thoracic, cage, the negative pressure is increased in the thoracic, cavity. It causes expansion of the lungs. During expira, tion, the thoracic cavity decreases in size to the preinspiratory position. Pressure in the thoracic cage also, comes back to the preinspiratory level. It compresses, the lung tissues so that, the air is expelled out of lungs.
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684 Section 9 t Respiratory System and Environmental Physiology, Collapsing Tendency of Lungs, Lungs are under constant threat to collapse even in, resting conditions because of certain factors., Factors Causing Collapsing Tendency of Lungs, Two factors are responsible for the collapsing tendency, of lungs:, 1. Elastic property of lung tissues: Elastic tissues of, lungs show constant recoiling tendency and try to, collapse the lungs, 2. Surface tension: It is the tension exerted by the fluid, secreted from alveolar epithelium on the surface of, alveolar membrane., Fortunately, there are some factors, which save the, lungs from collapsing., Factors Preventing Collapsing Tendency, of Lungs, In spite of elastic property of lungs and surface tension, in the alveoli of lungs, the collapsing tendency of lungs, is prevented by two factors:, 1. Intrapleural pressure: It is the pressure in the, pleural cavity, which is always negative (see below)., Because of negativity, it keeps the lungs expanded, and prevents the collapsing tendency of lungs, produced by the elastic tissues., 2. Surfactant: It is a substance secreted in alveolar epi, thelium. It reduces surface tension and prevents the, collapsing tendency produced by surface tension., Surfactant, Surfactant is a surface acting material or agent that is, responsible for lowering the surface tension of a fluid., Surfactant that lines the epithelium of the alveoli in lungs, is known as pulmonary surfactant and it decreases the, surface tension on the alveolar membrane., Source of secretion of pulmonary surfactant, Pulmonary surfactant is secreted by two types of cells:, 1. Type II alveolar epithelial cells in the lungs, which, are called surfactant secreting alveolar cells or, pneumocytes. Characteristic feature of these cells is, the presence of microvilli on their alveolar surface., 2. Clara cells, which are situated in the bronchioles., These cells are also called bronchiolar exocrine, cells., Chemistry of surfactant, Surfactant is a lipoprotein complex formed by lipids, especially phospholipids, proteins and ions., , 1. Phospholipids: Phospholipids form about 75%, of the surfactant. Major phospholipid present in, the surfactant is dipalmitoylphosphatidylcholine, (DPPC)., 2. Other lipids: Other lipid substances of surfactant are, triglycerides and phosphatidylglycerol (PG)., 3. Proteins: Proteins of the surfactant are called, specific surfactant proteins. There are four main, surfactant proteins, called SPA, SPB, SPC and, SPD. SPA and SPD are hydrophilic, while SPB, and SPC are hydrophobic. Surfactant proteins are, vital components of surfactant and the surfactant, becomes inactive in the absence of proteins., 4. Ions: Ions present in the surfactant are mostly, calcium ions., Formation of surfactant, Type II alveolar epithelial cells and Clara cells have, a special type of membrane bound organelles called, lamellar bodies, which form the intracellular source of, surfactant. Laminar bodies contain surfactant phos, pholipids and surfactant proteins. These materials are, synthesized in endoplasmic reticulum and stored in, laminar bodies., By means of exocytosis, lipids and proteins of, lamellar bodies are released into surface fluid lining the, alveoli. Here, in the presence of surfactant proteins and, calcium, the phospholipids are arranged into a lattice, (meshwork) structure called tubular myelin. Tubular, myelin is in turn converted into surfactant in the form of, a film that spreads over the entire surface of alveoli., Most of the surfactant is absorbed into the type II, alveolar cells, catabolized and the products are loaded, into lamellar bodies for recycling., Factors necessary for the formation, and spreading of surfactant, Formation of surfactant requires many substances. For, mation of tubular myelin requires DPPC, PG and the, hydrophobic proteins, SPB and SPC. Formation of, surfactant film requires SPB, SPC and PG., Type II alveolar epithelial cells occupy only about, 5% of alveolar surface. However, the surfactant must, spread over the entire alveolar surface. It is facilitated, by PG and calcium ions., Glucocorticoids play important role in the formation, of surfactant., Functions of surfactant, 1. Surfactant reduces the surface tension in the, alveoli of lungs and prevents collapsing tendency, of lungs.
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Chapter 120 t Mechanics of Respiration 685, Surfactant acts by the following mechanism:, Phospholipid molecule in the surfactant has two, portions. One portion of the molecule is hydrophilic. This portion dissolves in water and lines, the alveoli. Other portion is hydrophobic and it is, directed towards the alveolar air. This surface of the, phospholipid along with other portion spreads over, the alveoli and reduces the surface tension. SPB, and SPC play active role in this process., 2. Surfactant is responsible for stabilization of the, alveoli, which is necessary to withstand the collaps, ing tendency., 3. It plays an important role in the inflation of lungs, after birth. In fetus, the secretion of surfactant, begins after the 3rd month. Until birth, the lungs, are solid and not expanded. Soon after birth, the, first breath starts because of the stimulation of, respiratory centers by hypoxia and hypercapnea., Although the respiratory movements are attempted, by the infant, the lungs tend to collapse repeatedly., And, the presence of surfactant in the alveoli, prevents the lungs from collapsing., 4. Another important function of surfactant is its role, in defense within the lungs against infection and, inflammation. Hydrophilic proteins SPA and SPD, destroy the bacteria and viruses by means of, opsonization. These two proteins also control the, formation of inflammatory mediators., Effect of deficiency of surfactant – respiratory, distress syndrome, Absence of surfactant in infants, causes collapse of, lungs and the condition is called respiratory distress, syndrome or hyaline membrane disease. Deficiency, of surfactant occurs in adults also and it is called adult, , intrathoracic pressure since it is exerted in the whole, , of thoracic cavity., Normal Values, Respiratory pressures are always expressed in relation, to atmospheric pressure, which is 760 mm Hg. Under, physiological conditions, the intrapleural pressure is, always negative., Normal values are:, 1. At the end of normal inspiration:, –6 mm Hg (760 – 6 = 754 mm Hg), 2. At the end of normal expiration:, –2 mm Hg (760 – 2 = 758 mm Hg), 3. At the end of forced inspiration:, –30 mm Hg, 4. At the end of forced inspiration with closed glottis, (Müller maneuver):, –70 mm Hg, 5. At the end of forced expiration with closed glottis, (Valsalva maneuver):, +50 mm Hg., Cause for Negativity of Intrapleural Pressure, Pleural cavity is always lined by a thin layer of fluid that, is secreted by the visceral layer of pleura. This fluid, is constantly pumped from the pleural cavity into the, lymphatic vessels. Pumping of fluid creates the negative, pressure in the pleural cavity., Intrapleural pressure becomes positive in Valsalva, maneuver (Chapter 104) and in some pathological condi, tions such as pneumothorax, hydrothorax, hemothorax, and pyothorax., , respiratory distress syndrome (ARDS)., , In addition, the deficiency of surfactant increases, the susceptibility for bacterial and viral infections., , RESPIRATORY PRESSURES, Two types of pressures are exerted in the thoracic, cavity and lungs during process of respiration:, 1. Intrapleural pressure or intrathoracic pressure, 2. Intraalveolar pressure or intrapulmonary pressure., INTRAPLEURAL PRESSURE, Definition, Intrapleural pressure is the pressure existing in pleural, cavity, that is, in between the visceral and parietal layers, of pleura. It is exerted by the suction of the fluid that, lines the pleural cavity (Fig. 120.1). It is also called, , Measurement, Intrapleural pressure is measured by direct method and, indirect method. In the direct method, the intrapleural, pressure is determined by introducing a needle into the, pleural cavity and connecting the needle to a mercury, manometer. In indirect method, intrapleural pressure, is measured by introducing the esophageal balloon,, which is connected to a manometer. Intrapleural, pressure is considered as equivalent to the pressure, existing in the esophagus., Significance of Intrapleural Pressure, Throughout the respiratory cycle intrapleural pressure, remains lower than intraalveolar pressure. This keeps, the lungs always inflated.
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686 Section 9 t Respiratory System and Environmental Physiology, , FIGURE 120.1: Changes in respiratory pressures during inspiration and expiration., ‘0’ indicates the normal atmospheric pressure (760 mm Hg)., , Intrapleural pressure has two important functions:, 1. It prevents the collapsing tendency of lungs, 2. Because of the negative pressure in thoracic, region, larger veins and vena cava are enlarged,, i.e. dilated. Also, the negative pressure acts like, suction pump and pulls the venous blood from, lower part of body towards the heart against, gravity. Thus, the intrapleural pressure is respon, sible for venous return. So, it is called the respiratory pump for venous return (Chapter 98)., INTRA-ALVEOLAR PRESSURE, , 1., 2., 3., 4., 5., , Normal values are:, During normal inspiration:, –1 mm Hg (760 – 1 = 759 mm Hg), During normal expiration:, +1 mm Hg (760 + 1 = 761 mm Hg), At the end of inspiration and expiration:, Equal to atmospheric pressure (760 mm Hg), During forced inspiration with closed glottis, (Müller maneuver): –80 mm Hg, During forced expiration with closed glottis, (Valsalva maneuver): +100 mm Hg., , Definition, , Measurement, , Intraalveolar pressure is the pressure existing in the, alveoli of the lungs. It is also known as intrapulmonary, , Intraalveolar pressure is measured, plethysmograph (Chapter 121)., , pressure., , Normal Values, Normally, intraalveolar pressure is equal to the atmos, pheric pressure, which is 760 mm Hg. It becomes negative, during inspiration and positive during expiration., , by, , using, , Significance of Intra-alveolar Pressure, 1. Intraalveolar pressure causes flow of air, in and out of alveoli. During inspiration, the, intraalveolar pressure becomes negative, so, the atmospheric air enters the alveoli. During
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Chapter 120 t Mechanics of Respiration 687, expiration, intraalveolar pressure becomes, positive. So, air is expelled out of alveoli., 2. Intraalveolar pressure also helps in exchange of, gases between the alveolar air and the blood., Transpulmonary Pressure, Transpulmonary pressure is the pressure difference, between intraalveolar pressure and intrapleural, pressure. It is the measure of elastic forces in lungs,, which is responsible for collapsing tendency of lungs., , COMPLIANCE, , Specific Compliance, The term specific compliance is introduced to assess, the stiffness of lung tissues more accurately. Specific, compliance is the compliance per liter of lung volume., It is usually reported for expiration at functional residual, capacity. It is the compliance divided by functional, residual capacity., Compliance of lungs, Specific compliance, =, of lungs, Functional residual capacity, Functional residual capacity is the volume of air, present in lungs at the end of normal expiration., , DEFINITION, Compliance is the ability of the lungs and thorax to, expand or it is the expansibility of lungs and thorax. It, is defined as the change in volume per unit change in, the pressure., , TYPES OF COMPLIANCE, Compliance is of two types:, 1. Static compliance, 2. Dynamic compliance., , Significance of Determining Compliance, , 1. Static Compliance, , Determination of compliance is useful as it is the, measure of stiffness of lungs. Stiffer the lungs, less is, the compliance., , Static compliance is the compliance measured under, static conditions, i.e. by measuring pressure and, volume when breathing does not take place (see below)., Static compliance is the pressure required to overcome, the elastic resistance of respiratory system for a given, tidal volume under zero flow (static) condition., , NORMAL VALUES, Compliance is expressed by two ways:, 1. In relation to intraalveolar pressure, 2. In relation to intrapleural pressure., Compliance in Relation to Intra-alveolar Pressure, Compliance is the volume increase in lungs per unit, increase in the intraalveolar pressure., 1. Compliance of lungs and thorax together:, 130 mL/1 cm H2O pressure, 2. Compliance of lungs alone:, 220 mL/1 cm H2O pressure., , 2. Dynamic Compliance, Dynamic compliance is the compliance measured during, dynamic conditions, i.e. during breathing., , Static Compliance Vs Dynamic Compliance, In healthy subjects, there is little difference between, static and dynamic compliance. In patients with stiff, lungs, the dynamic compliance decreases while little, change occurs in the static compliance., , Compliance in Relation to Intrapleural Pressure, Compliance is the volume increase in lungs per unit, decrease in the intrapleural pressure., 1. Compliance of lungs and thorax together:, 100 mL/1 cm H2O pressure, 2. Compliance of lungs alone:, 200 mL/1 cm H2O pressure., Thus, if lungs could be removed from thorax,, the expansibility (compliance) of lungs alone will be, doubled. It is because of the absence of inertia and, restriction exerted by the structures of thoracic cage,, which interfere with expansion of lungs., , MEASUREMENT OF COMPLIANCE, Measurement of Static Compliance, To measure the static compliance, the subject is, asked to inspire air periodically at regular steps from, a spirometer. In each step, a known volume of air is, inspired. At the end of each step, intrapleural pressure, is measured by means of an esophageal balloon., Then, the air is expired in steps until the volume returns, to original preinspiratory level. Intrapleural pressure is, measured at the end of each step.
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688 Section 9 t Respiratory System and Environmental Physiology, Values of volume and pressure are plotted to obtain, a curve, which is called pressure-volume curve. From, this curve compliance can be calculated. This curve, also shows the difference in inspiration and expiration, (Fig. 120.2)., Measurement of Dynamic Compliance, Dynamic compliance is measured during normal, breathing. It is measured by determining the lung volume, and esophageal pressure (intrapleural pressure) at the, end of inspiration and expiration when the lungs are, apparently stationary., APPLIED PHYSIOLOGY, Increase in Compliance, Compliance increases due to loss of elastic property, of lung tissues, which occurs both in physiological and, pathological conditions:, 1. Physiological condition: Old age, 2. Pathological condition: Emphysema (Fig. 120.3)., , FIGURE 120.2: Pressurevolume curve, , Decrease in Compliance, Compliance decreases in several pathological condi, tions such as:, 1. Deformities of thorax like kyphosis and scoliosis, (Chapter 68), 2. Fibrotic pleurisy (inflammation of pleura resulting in, fibrosis), 3. Paralysis of respiratory muscles, 4. Pleural effusion (Chapter 127), 5. Abnormal thorax such as pneumothorax, hydro, thorax, hemothorax and pyothorax (Chapter 127)., , WORK OF BREATHING, Work of breathing is the work done by respiratory, muscles during breathing to overcome the resistance, in thorax and respiratory tract., , FIGURE 120.3: Variations in lung compliance, , WORK DONE BY RESPIRATORY MUSCLES, During respiratory processes, inspiration is active, process and the expiration is a passive process. So,, during quiet breathing, respiratory muscles perform the, work only during inspiration and not during expiration., , 1. Airway resistance, 2. Elastic resistance of lungs and thorax, 3. Nonelastic viscous resistance., 1. Airway Resistance, , UTILIZATION OF ENERGY, During the work of breathing, the energy is utilized to, overcome three types of resistance:, , Airway resistance is the resistance offered to the, passage of air through respiratory tract. Resistance, increases during bronchiolar constriction, which in
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Chapter 120 t Mechanics of Respiration 689, , FIGURE 120.4: Work of breathing, , creases the work done by the muscles during breathing., Work done to overcome the airway resistance is called, airway resistance work., , 2. Elastic Resistance of Lungs and Thorax, Energy is required to expand lungs and thorax against, the elastic force. Work done to overcome this elastic, resistance is called compliance work., , 3. Non-elastic Viscous Resistance, Energy is also required to overcome the viscosity of, lung tissues and tissues of thoracic cage. Work done, to overcome this viscous resistance is called tissue, resistance work., , Above factors are explained by the curve that, shows the relation between lung volume and pleural, pressure (Fig. 120.4).
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Pulmonary Function Tests, , , , , , , , , , , , , Chapter, , 121, , INTRODUCTION, LUNG VOLUMES, LUNG CAPACITIES, MEASUREMENT OF LUNG VOLUMES AND CAPACITIES, MEASUREMENT OF FUNCTIONAL RESIDUAL CAPACITY AND RESIDUAL VOLUME, VITAL CAPACITY, FORCED EXPIRATORY VOLUME OR TIMED VITAL CAPACITY, RESPIRATORY MINUTE VOLUME, MAXIMUM BREATHING CAPACITY OR MAXIMUM VENTILATION VOLUME, PEAK EXPIRATORY FLOW RATE, RESTRICTIVE AND OBSTRUCTIVE RESPIRATORY DISEASES, , INTRODUCTION, , Dynamic Lung Function Tests, , Pulmonary function tests or lung function tests are use, ful in assessing the functional status of the respiratory, system both in physiological and pathological condi, tions. Lung function tests are based on the measurement, of volume of air breathed in and out in quiet breathing, and forced breathing. These tests are carried out mostly, by using spirometer., , Dynamic lung function tests are based on time, i.e. the, rate at which air flows into or out of lungs. These tests, include forced vital capacity, forced expiratory volume,, maximum ventilation volume and peak expiratory flow., Dynamic lung function tests are useful in deter, mining the severity of obstructive and restrictive lung, diseases., , TYPES OF LUNG FUNCTION TESTS, Lung function tests are of two types:, 1. Static lung function tests, 2. Dynamic lung function tests., Static Lung Function Tests, Static lung function tests are based on volume of, air that flows into or out of lungs. These tests do not, depend upon the rate at which air flows., Static lung function tests include static lung volumes, and static lung capacities., , LUNG VOLUMES, Static lung volumes are the volumes of air breathed, by an individual. Each of these volumes represents, the volume of air present in the lung under a specified, static condition (specific position of thorax)., Static lung volumes are of four types:, 1. Tidal volume, 2. Inspiratory reserve volume, 3. Expiratory reserve volume, 4. Residual volume.
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Chapter 121 t Pulmonary Function Tests 691, TIDAL VOLUME, Tidal volume (TV) is the volume of air breathed in and, out of lungs in a single normal quiet respiration. Tidal, volume signifies the normal depth of breathing., Normal Value, 500 mL (0.5 L)., INSPIRATORY RESERVE VOLUME, Inspiratory reserve volume (IRV) is an additional volume, of air that can be inspired forcefully after the end of, normal inspiration., Normal Value, 3,300 mL (3.3 L)., EXPIRATORY RESERVE VOLUME, Expiratory reserve volume (EVR) is the additional, volume of air that can be expired out forcefully, after, normal expiration., Normal Value, 1,000 mL (1 L)., , Residual volume is significant because of two, reasons:, 1. It helps to aerate the blood in between breathing, and during expiration, 2. It maintains the contour of the lungs., Normal Value, 1,200 mL (1.2 L), , LUNG CAPACITIES, Static lung capacities are the combination of two or, more lung volumes., Static lung capacities are of four types:, 1. Inspiratory capacity, 2. Vital capacity, 3. Functional residual capacity, 4. Total lung capacity., INSPIRATORY CAPACITY, Inspiratory capacity (IC) is the maximum volume of air, that is inspired after normal expiration (end expiratory, position). It includes tidal volume and inspiratory reserve, volume (Fig. 121.1)., IC = TV + IRV, = 500 + 3,300 = 3,800 mL, , RESIDUAL VOLUME, Residual volume (RV) is the volume of air remaining in lungs even after forced expiration. Normally,, lungs cannot be emptied completely even by forceful, expiration. Some quantity of air always remains in the, lungs even after the forced expiration., , VITAL CAPACITY (VC), Vital capacity (VC) is the maximum volume of air that, can be expelled out forcefully after a deep (maximal), inspiration. VC includes inspiratory reserve volume,, tidal volume and expiratory reserve volume., , FIGURE 121.1: Lung volumes and capacities. TV = Tidal volume, IRV = Inspiratory reserve volume,, ERV = Expiratory reserve volume, RV = Residual volume, IC = Inspiratory capacity, FRC = Functional, residual capacity, VC = Vital capacity, TLC = Total lung capacity.
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692 Section 9 t Respiratory System and Environmental Physiology, VC = IRV + TV + ERV, = 3,300 + 500 + 1,000 = 4,800 mL, Vital capacity is significant physiologically and its, determination is useful in clinical diagnosis as explained, later in this chapter., FUNCTIONAL RESIDUAL CAPACITY, Functional residual capacity (FRC) is the volume of air, remaining in lungs after normal expiration (after normal, tidal expiration). Functional residual capacity includes, expiratory reserve volume and residual volume., FRC = ERV + RV, = 1,000 + 1,200 = 2,200 mL, TOTAL LUNG CAPACITY, Total lung capacity (TLC) is the volume of air present, in lungs after a deep (maximal) inspiration. It includes, all the volumes., TLC = IRV + TV + ERV + RV, = 3,300 + 500 + 1,000 + 1,200 = 6,000 mL, , MEASUREMENT OF LUNG VOLUMES, AND CAPACITIES, Spirometry is the method to measure lung volumes and, capacities. Simple instrument used for this purpose is, called spirometer. Modified spirometer is known as, respirometer. Nowadays plethysmograph is also used, to measure lung volumes and capacities., SPIROMETER, Spirometer is made up of metal and it contains two, chambers namely outer chamber and inner chamber, (Fig. 121.2). Outer chamber is called the water cham, ber because it is filled with water. A floating drum is, immersed in the water in an inverted position. Drum is, counter balanced by a weight. Weight is attached to the, top of the inverted drum by means of string or chain. A, pen with ink is attached to the counter weight. Pen is, made to write on a calibrated paper, which is fixed to a, recording device., Inner chamber is inverted and has a small hole at, the top. A long metal tube passes through the inner, , FIGURE 121.2: Spirometer. During expiration, the air enters the spirometer from lungs., Inverted drum moves up and the pen draws a downward curve on the recording drum.
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Chapter 121 t Pulmonary Function Tests 693, chamber from the bottom towards the top. Upper end of, this tube reaches the top portion of the inner chamber., Then the tube passes through a hole at the top of inner, chamber and penetrates into outer water chamber, above the level of water. A rubber tube is connected, to the outer end of the metal tube. At the other end of, this rubber tube, a mouthpiece is attached. Subject, respires through this mouthpiece by closing the nose, with a nose clip., When the subject breathes with spirometer, during, expiration, drum moves up and the counter weight comes, down. Reverse of this occurs when the subject breathes, the air from the spirometer, i.e. during inspiration. Up, ward and downward movements of the counter weight, are recorded in the form of a graph. Upward deflection, of the curve in the graph shows inspiration and the, downward deflection denotes expiration., Spirometer is used only for a single breath. Repeated, cycles of respiration cannot be recorded by using this, instrument because carbon dioxide accumulates in the, spirometer and oxygen or fresh air cannot be provided, to the subject., Respirometer, Respirometer is the modified spirometer. It has provision, for removal of carbon dioxide and supply of oxygen., Carbon dioxide is removed by placing soda lime, inside the instrument. Oxygen is supplied to the, instrument from the oxygen cylinder, by a suitable valve, system., , Oxygen is filled in the inverted drum above water, level and the subject can breathe in and out with, instrument for about 6 minutes and recording can be, done continuously., Spirogram, Spirogram is the graphical record of lung volumes and, capacities using spirometer. Upward deflection of the, spirogram denotes inspiration and the downward curve, indicates expiration (Fig. 121.3). In order to determine, the lung volumes and capacities, following four levels, are to be noted in spirogram:, 1. Normal end expiratory level, 2. Normal end inspiratory level, 3. Maximum expiratory level, 4. Maximum inspiratory level., COMPUTERIZED SPIROMETER, Computerized spirometer is the solid state electronic, equipment. It does not contain a drum or water, chamber. Subject has to respire into a sophisticated, transducer, which is connected to the instrument by, means of a cable., Disadvantages of Spirometry, By using simple spirometer, respirometer or comput, erized spirometer, not all the lung volumes and lung, capacities can be measured., , FIGURE 121.3: Spirogram. TV = Tidal volume, IRV = Inspiratory reserve volume, ERV = Expiratory reserve volume, RV =, Residual volume, IC = Inspiratory capacity, FRC = Functional residual capacity, VC = Vital capacity, TLC = Total lung capacity.
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694 Section 9 t Respiratory System and Environmental Physiology, Volume, which cannot be measured by spirometry,, is the residual volume. Capacities, which include, residual volume also cannot be measured. Capacities, that include residual volume are functional residual, capacity and total lung capacity., Volume and capacities, which cannot be measured, by spirometry, are measured by nitrogen washout, technique or helium dilution technique or by body, , Measured Values, , plethysmograph., , Calculation, , PLETHYSMOGRAPHY, , From the above data, the functional residual capacity, of the subject is calculated in the following way:, , Plethysmography is a technique used to measure all the, lung volumes and capacities. It is explained later., , MEASUREMENT OF FUNCTIONAL, RESIDUAL CAPACITY AND, RESIDUAL VOLUME, Residual volume and the functional residual capacity, cannot be measured by spirometer and can be deter, mined by three methods:, 1. Helium dilution technique, 2. Nitrogen washout method, 3. Plethysmography., , For example, the following data of a subject are obtained, from the experiment:, 1. Initial volume of air in respirometer = 5 L (5,000 mL), 2. Initial concentration of helium in respirometer = 15%, 3. Final concentration of helium in respirometer = 10%., , FRC =, , V (C1 – C2), C2, , FRC =, , 5,000 (15/100 – 10/100), , mL, , 10/100, =, , 5,000 (5/100), , mL, , 10/100, =, , 5,000 × 5, , mL, , 10, = 2,500 mL, , 1. HELIUM DILUTION TECHNIQUE, Procedure to Measure Functional, Residual Capacity, Respirometer is filled with air containing a known, quantity of helium. Initially, the subject breathes, normally. Then, after the end of expiration, subject, breathes from respirometer. Helium from respirometer, enters the lungs and starts mixing with air in lungs., After few minutes of breathing, concentration of helium, in the respirometer becomes equal to concentration, of helium in the lungs of subject. It is called the, equilibration of helium. After equilibration of helium, between respirometer and lungs, concentration of, helium in respirometer is determined (Fig. 121.4)., Functional residual capacity is calculated by the, formula:, FRC =, , V (C1 – C2), , C2, Where,, C1, = Initial concentration of helium in the, respirometer, C2, = Final concentration of helium in the, respirometer, V, = Initial volume of air in the respirometer., , Thus, the functional residual capacity in this subject, is 2,500 mL., Procedure to Measure Residual Volume, To determine functional residual capacity, the subject, starts breathing with respirometer after the end of, normal expiration. To measure residual volume, the, subject should start breathing from the respirometer, after forced expiration., 2. NITROGEN WASHOUT METHOD, Normally, concentration of nitrogen in air is 80%. So, if, total quantity of nitrogen in the lungs is measured, the, volume of air present in lungs can be calculated., Procedure to Measure Functional, Residual Capacity, Subject is asked to breathe normally. At the end of normal, expiration, the subject inspires pure oxygen through a, valve and expires into a Douglas bag. This procedure is, repeated for 6 to 7 minutes, until the nitrogen in lungs, is displaced by oxygen. Nitrogen comes to the Douglas, bag. Afterwards, following factors are measured to, calculate functional residual capacity.
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Chapter 121 t Pulmonary Function Tests 695, Measured Values, For example, the following data are obtained from the, experiment with a subject:, i. Volume of air collected, ii. Concentration of nitrogen, in the collected air, iii. Normal concentration of, nitrogen in the air., , = 40 L (40,000 mL), = 5%, = 80%, , Calculation, From the above data, the functional residual capacity of, the subject is calculated in the following way:, FRC =, , C1 × V, C2, , FRC =, , 5/100 × 40,000, , mL, , 80/100, =, , 5 × 40,000, , mL, , 80, = 2,500 mL., Thus, functional residual capacity in this subject is, 2,500 mL., Procedure to Measure Residual Volume, , FIGURE 121.4: Measurement of functional residual, capacity by using helium, , Calculation, i. Volume of air collected in Douglas bag, ii. Concentration of nitrogen in Douglas bag., By using the data, the functional residual capacity is, calculated by using the formula:, FRC =, Where,, V, =, C1, =, C2, , =, , C1 × V, C2, Volume of air collected, Concentration of nitrogen in the collected, air, Normal concentration of nitrogen in the, air., , To measure the functional residual capacity, the subject, starts inhaling pure oxygen after the end of normal, expiration and to determine the residual volume, the, subject starts breathing pure oxygen after forceful, expiration., 3. PLETHYSMOGRAPHY, Plethysmography is a technique to study the variations, in the size or volume of a part of the body such as, limb. Plethysmograph is the instrument used for this, purpose. Whole body plethysmograph is the instrument, used to measure the lung volumes including residual, volume., Plethysmography is based on Boyle’s law of gas,, which states that the volume of a sample of gas is, inversely proportional to the pressure of that gas at, constant temperature., Subject sits in an airtight chamber of the whole, body plethysmograph and breathes normally through, a mouthpiece connected to a flow transducer called, pneumotachograph. It detects the volume changes
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696 Section 9 t Respiratory System and Environmental Physiology, during different phases of respiration. After normal, breathing for few minutes, the subject breathes rapidly, with maximum force. During maximum expiration, the, lung volume decreases very much. But volume of gas, in the chamber increases with decrease in pressure., By measuring the volume and pressure changes in, side the chamber, volume of lungs is calculated by, using the formula:, P1 × V = P2 (V – ∆ V), Where,, P1 and P2 = Pressure changes, V = Functional residual capacity., , 1., 2., 3., 4., 5., 6., 7., 8., 9., 10., 11., , Asthma, Emphysema, Weakness or paralysis of respiratory muscle, Pulmonary congestion, Pneumonia, Pneumothorax, Hemothorax, Pyothorax, Hydrothorax, Pulmonary edema, Pulmonary tuberculosis., , VITAL CAPACITY, , Measurement, , DEFINITION, , Vital capacity is measured by spirometry. The subject is, asked to take a deep inspiration and expire forcefully., , Vital capacity is the maximum volume of air that can be, expelled out of lungs forcefully after a maximal or deep, inspiration., , FORCED VITAL CAPACITY, , LUNG VOLUMES INCLUDED, IN VITAL CAPACITY, Vital capacity includes inspiratory reserve volume, tidal, volume and expiratory reserve volume., NORMAL VALUE, VC = IRV + TV + ERV, = 3,300 + 500 + 1,000 = 4,800 mL., VARIATIONS OF VITAL CAPACITY, Physiological Variations, 1. Sex: In females, vital capacity is less than in, males, 2. Body built: Vital capacity is slightly more in, heavily built persons, 3. Posture: Vital capacity is more in standing, position and less in lying position, 4. Athletes: Vital capacity is more in athletes, 5. Occupation: Vital capacity is decreased in, people with sedentary jobs. It is increased in, persons who play musical wind instruments, such as bugle and flute., Pathological Variations, Vital capacity is decreased in the following respiratory, diseases:, , Forced vital capacity (FVC) is the volume of air that, can be exhaled forcefully and rapidly after a maximal or, deep inspiration. It is a dynamic lung capacity., Normally FVC is equal to VC. However in some, pulmonary diseases, FVC is decreased., , FORCED EXPIRATORY VOLUME, OR TIMED VITAL CAPACITY, DEFINITION, Forced expiratory volume (FEV) is the volume of air,, which can be expired forcefully in a given unit of time, (after a deep inspiration). It is also called timed vital, capacity or forced expiratory vital capacity (FEVC). It, is a dynamic lung volume., FEV1 = Volume of air expired forcefully in 1 second, FEV2 = Volume of air expired forcefully in 2 seconds, FEV3 = Volume of air expired forcefully in 3 seconds., NORMAL VALUES, Forced expiratory volume in persons with normal, respiratory functions is as follows:, FEV1 = 83% of total vital capacity, FEV2 = 94% of total vital capacity, FEV3 = 97% of total vital capacity, After 3rd second = 100% of total vital capacity.
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Chapter 121 t Pulmonary Function Tests 697, SIGNIFICANCE OF DETERMINING FEV, , MEASUREMENT, , Vital capacity may be almost normal in some of the, respiratory diseases. However, the FEV has great, diagnostic value, as it is decreased significantly in some, respiratory diseases., It is very much decreased in obstructive diseases, like asthma and emphysema. It is slightly reduced in, some restrictive respiratory diseases like fibrosis of, lungs (Fig. 121.5)., , Subject is asked to breathe forcefully and rapidly with, a respirometer for 15 seconds. Volume of air inspired, and expired is measured from the spirogram. From this, value, the MBC is calculated for 1 minute., For example, MBC in 12 seconds = 32 L, MBC per minute =, , 32, , × 60 L, , 12, = 160 L, , RESPIRATORY MINUTE VOLUME, DEFINITION, , PEAK EXPIRATORY FLOW RATE, , Respiratory minute volume (RMV) is the volume of, air breathed in and out of lungs every minute. It is the, product of tidal volume (TV) and respiratory rate (RR)., , DEFINITION, , RMV = TV × RR, = 500 × 12 = 6,000 mL., , Peak expiratory flow rate (PEFR) is the maximum rate, at which the air can be expired after a deep inspiration., NORMAL VALUE, , NORMAL VALUE, , In normal persons, it is 400 L/minute., , Normal respiratory minute volume is 6 L., , MEASUREMENT, , VARIATIONS, , Peak expiratory flow rate is measured by using Wright, peak flow meter or a mini peak flow meter., , Respiratory minute volume increases in physiological, conditions such as voluntary hyperventilation, exercise, and emotional conditions. It is reduced in respiratory, diseases., , MAXIMUM BREATHING CAPACITY OR, MAXIMUM VENTILATION VOLUME, DEFINITION, Maximum breathing capacity (MBC) is the maximum, volume of air, which can be breathed in and out of, lungs by forceful respiration (hyperventilation: increase, in rate and force of respiration) per minute. It is also, called maximum ventilation volume (MVV)., MBC is a dynamic lung capacity and it is reduced in, respiratory diseases., NORMAL VALUE, In healthy adult male, it is 150 to 170 L/minute and in, females, it is 80 to 100 L/minute., , SIGNIFICANCE OF DETERMINING PEFR, Determination of PEFR rate is useful for assessing, the respiratory diseases especially to differentiate the, obstructive and restrictive diseases. Generally, PEFR, is reduced in all type of respiratory disease. However,, reduction is more significant in the obstructive diseases, than in the restrictive diseases., Thus, in restrictive diseases, the PEFR is 200 L/min, ute and in obstructive diseases, it is only 100 L/minute., , RESTRICTIVE AND OBSTRUCTIVE, RESPIRATORY DISEASES, Diseases of respiratory tract are classified into two, types:, 1. Restrictive respiratory disease, 2. Obstructive respiratory disease., These two types of respiratory diseases are deter, mined by lung functions tests, particularly FEV.
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698 Section 9 t Respiratory System and Environmental Physiology, , FIGURE 121.5: Forced expiratory volume. FEV = Forced expiratory volume.
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Chapter 121 t Pulmonary Function Tests 699, TABLE 121.1: Restrictive and obstructive respiratory diseases, Type, , Restrictive respiratory diseases, , Obstructive respiratory diseases, , Structures involved, , Disease, Polio myelitis, , CNS, , Myasthenia gravis, , CNS and thoracic cavity, , Flail chest (broken ribs), , Thoracic cavity, , Paralysis of diaphragm, , CNS, , Spinal cord diseases, , CNS, , Pleural effusion, , Thoracic cavity, , Asthma, Chronic bronchitis, Emphysema, Cystic fibrosis, , Lower respiratory tract, , Laryngotracheobronchitis, Epiglottis, Tumors, Severe cough and cold with phlegm, , Upper respiratory tract, , RESTRICTIVE RESPIRATORY DISEASE, , OBSTRUCTIVE RESPIRATORY DISEASE, , Restrictive respiratory disease is the abnormal res, piratory condition characterized by difficulty in inspiration. Expiration is not affected. Restrictive respiratory, disease may be because of abnormality of lungs,, thoracic cavity or/and nervous system., , Obstructive respiratory disease is the abnormal, respiratory condition characterized by difficulty in, expiration., Obstructive and respiratory diseases are listed in, Table 121.1.
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Chapter, , Ventilation, , 122, , VENTILATION, PULMONARY VENTILATION, , , , DEFINITION, NORMAL VALUE AND CALCULATION, , ALVEOLAR VENTILATION, , , , DEFINITION, NORMAL VALUE AND CALCULATION, , DEAD SPACE, , , , , , DEFINITION, TYPES, NORMAL VALUE, MEASUREMENT, , VENTILATION-PERFUSION RATIO, , , , , , , DEFINITION, NORMAL VALUE AND CALCULATION, SIGNIFICANCE, WASTED AIR AND WASTED BLOOD, VARIATIONS, , VENTILATION, , NORMAL VALUE AND CALCULATION, , In general, the word ‘ventilation’ refers to circulation, of replacement of air or gas in a space. In respiratory, physiology, ventilation is the rate at which air enters or, leaves the lungs. Ventilation in respiratory physiology, is of two types:, 1. Pulmonary ventilation, 2. Alveolar ventilation., , Normal value of pulmonary ventilation is 6,000 mL, (6 L)/minute. It is the product of tidal volume (TV) and, the rate of respiration (RR)., It is calculated by the formula:, , PULMONARY VENTILATION, , Pulmonary ventilation, = Tidal volume × Respiratory rate, = 500 mL × 12/minute, = 6,000 mL/minute., , DEFINITION, , ALVEOLAR VENTILATION, , Pulmonary ventilation is defined as the volume of air, moving in and out of respiratory tract in a given unit, of time during quiet breathing. It is also called minute, ventilation or respiratory minute volume (RMV)., Pulmonary ventilation is a cyclic process, by which, fresh air enters the lungs and an equal volume of air, leaves the lungs., , DEFINITION, Alveolar ventilation is the amount of air utilized for, gaseous exchange every minute., Alveolar ventilation is different from pulmonary, ventilation. In pulmonary ventilation, 6 L of air moves, in and out of respiratory tract every minute. But the
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Chapter 122 t Ventilation 701, whole volume of air is not utilized for exchange of, gases. Volume of air subjected for exchange of gases, is the alveolar ventilation. Air trapped in the respiratory, passage (dead space) does not take part in gaseous, exchange., , Wasted ventilation and wasted air, , NORMAL VALUE AND CALCULATION, , NORMAL VALUE OF DEAD SPACE, , Normal value of alveolar ventilation is 4,200 mL (4.2 L)/, minute., It is calculated by the formula:, , Volume of normal dead space is 150 mL. Under, normal conditions, physiological dead space is equal to, anatomical dead space. It is because, all the alveoli are, functioning and all the alveoli receive adequate blood, flow in normal conditions., Physiological dead space increases during res, piratory diseases, which affect the pulmonary blood flow, or the alveoli., , Alveolar ventilation, = (Tidal volume – Dead space) x Respiratory rate, = (500 – 150) mL × 12/minute, = 4,200 mL (4.2 L)/minute., , DEAD SPACE, DEFINITION, Dead space is defined as the part of the respiratory, tract, where gaseous exchange does not take place. Air, present in the dead space is called dead space air., TYPES OF DEAD SPACE, Dead space is of two types:, 1. Anatomical dead space, 2. Physiological dead space., Anatomical Dead Space, Anatomical dead space extends from nose up to termi, nal bronchiole. It includes nose, pharynx, trachea,, bronchi and branches of bronchi up to terminal, bronchioles. These structures serve only as the, passage for air movement. Gaseous exchange does, not take place in these structures., Physiological Dead Space, Physiological dead space includes anatomical dead, space plus two additional volumes., Additional volumes included in physiological dead, space are:, 1. Air in the alveoli, which are non-functioning. In some, respiratory diseases, alveoli do not function because, of dysfunction or destruction of alveolar membrane., 2. Air in the alveoli, which do not receive adequate, blood flow. Gaseous exchange does not take place, during inadequate blood supply., These two additional volumes are generally con, sidered as wasted ventilation., , Wasted ventilation is the volume of air that ventilates, physiological dead space. Wasted air refers to air that, is not utilized for gaseous exchange. Dead space air is, generally considered as wasted air., , MEASUREMENT OF DEAD SPACE –, NITROGEN WASHOUT METHOD, Dead space is measured by single breath nitrogen, washout method. The subject respires normally for few, minutes. Then, he takes a sudden inhalation of pure, oxygen., Oxygen replaces the air in dead space (air passage),, i.e. the dead space air contains only oxygen and it, pushes the other gases into alveoli., Now, the subject exhales through a nitrogen meter., Nitrogen meter shows the concentration of nitrogen in, expired air continuously., First portion of expired air comes from upper part, of respiratory tract or air passage, which contains only, oxygen. Next portion of expired air comes from the, alveoli, which contains nitrogen. Now, the nitrogen meter, shows the nitrogen concentration, which rises sharply, and reaches the plateau soon. By using data obtained, from nitrogen meter, a graph is plotted. From this graph,, the dead space is calculated (Fig. 122.1)., The graph has two areas, area without nitrogen, and area with nitrogen. Area of the graph is measured, by a planimeter or by computer. Area without nitrogen, indicates dead space air., It is calculated by the formula:, , Dead space =, , Area, without N2, , Volume of, × expired air, , Area, Area, with N2 + without N2, For example, in a subject:, Area with nitrogen, = 70 sq cm, Area without nitrogen = 30 sq cm, Volume of air expired = 500 mL
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702 Section 9 t Respiratory System and Environmental Physiology, , Dead space, , =, , =, , 30, , × 500, , 70 + 30, 30, , × 500, 100, = 150 mL., , VENTILATION-PERFUSION RATIO, DEFINITION, Ventilationperfusion ratio is the ratio of alveolar, ventilation and the amount of blood that perfuse the, alveoli., It is expressed as VA/Q. VA is alveolar ventilation and, Q is the blood flow (perfusion)., NORMAL VALUE AND CALCULATION, Normal Value, Normal value of ventilationperfusion ratio is about, 0.84., Calculation, Alveolar ventilation is calculated by the formula:, Ventilationperfusion ratio, , =, , Alveolar ventilation, Pulmonary blood flow, , Alveolar ventilation = (Tidal volume – Dead space) ×, Respiratory rate, = (500 – 150) mL × 12/minute, = 4,200 mL/minute, Blood flow through alveoli, (Pulmonary blood flow) = 5,000 mL/minute, Therefore,, 4,200, Ventilationperfusion ratio =, 5,000, =, , 0.84, , SIGNIFICANCE OF VENTILATIONPERFUSION RATIO, Ventilation-perfusion ratio signifies the gaseous exchange. It is affected if there is any change in alveolar, ventilation or in blood flow., Ventilation without perfusion = dead space, Perfusion without ventilation = shunt, WASTED AIR AND WASTED BLOOD, Ventilationperfusion ratio is not perfect because of exist, ence of two factors on either side of alveolar membrane., , FIGURE 122.1: Measurement of dead space, , These factors are:, 1. Physiological dead space, which includes wasted, air (see above), 2. Physiological shunt, which includes wasted blood, (Chapter 119)., VARIATIONS IN VENTILATIONPERFUSION RATIO, Physiological Variation, 1. Ratio increases, if ventilation increases without any, change in blood flow, 2. Ratio decreases, if blood flow increases without any, change in ventilation, 3. In sitting position, there is reduction in blood flow, in the upper part of the lungs (zone 1) than in the, lower part (zone 3). Therefore, in zone 1 of lungs, ventilationperfusion ratio increases three times., At the same time, in zone 3 of the lungs, because, of increased blood flow ventilation-perfusion ratio, decreases (Chapter 119)., Pathological Variation, In chronic obstructive pulmonary diseases (COPD),, ventilation is affected because of obstruction and des, truction of alveolar membrane. So, ventilationperfusion, ratio reduces greatly.
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Chapter, , Inspired Air, Alveolar Air, and Expired Air, , 123, , INSPIRED AIR, , , , DEFINITION, COMPOSITION, , ALVEOLAR AIR, , , , , , DEFINITION, COMPOSITION, RENEWAL, METHOD OF COLLECTION, , EXPIRED AIR, , , , , DEFINITION, COMPOSITION, METHOD OF COLLECTION, , INSPIRED AIR, , ALVEOLAR AIR, , DEFINITION, , DEFINITION, , Inspired air is the atmospheric air, which is inhaled, during inspiration., , Alveolar air is the air present in alveoli of lungs. Its, composition is given in Table 123.1., , COMPOSITION, , Alveolar Air Vs Inspired Air, , Composition of inspired air is given in Table 123.1., , Alveolar air is different from inspired air in four ways:, , TABLE 123.1: Composition of inspired air, alveolar air and expired air, Air, , Gas, Oxygen, Carbon dioxide, Nitrogen, Water vapor, etc., Total, , Inspired, (atmospheric) air, , Alveolar air, , Expired air, , Content, (mL%), , Partial, pressure, (mm Hg), , Content, (mL%), , Partial, pressure, (mm Hg), , Content, (mL%), , Partial, pressure, (mm Hg), , 20.84, , 159.00, , 13.60, , 104.00, , 15.70, , 120.00, , 0.04, , 0.30, , 5.30, , 40.00, , 3.60, , 27.00, , 78.62, , 596.90, , 74.90, , 569.00, , 74.50, , 566.00, , 0.50, , 3.80, , 6.20, , 47.00, , 6.20, , 47.00, , 100.00, , 760.00, , 100.00, , 760.00, , 100.00, , 760.00
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704 Section 9 t Respiratory System and Environmental Physiology, 1. Alveolar air is partially replaced by the atmospheric, air during each breath, 2. Oxygen diffuses from the alveolar air into pulmonary, capillaries constantly, 3. Carbon dioxide diffuses from pulmonary blood into, alveolar air constantly, 4. Dry atmospheric air is humidified, while passing, through respiratory passage before entering the, alveoli (Table 123.1)., COMPOSITION, Composition of alveolar air is given in Table 123.1., RENEWAL, , Alveolar air is collected by using Haldane-Priestely, tube. This tube consists of a canvas rubber tube, which, is 1 m long and having a diameter of 2.5 cm. It is opened, on both ends., A mouthpiece is fitted at one end of the tube. Near, the mouthpiece, there is a side tube, which is fixed, with a sampling tube. Mouthpiece and the side tube, are interconnected by means of a three-way cock., By keeping the mouthpiece in the mouth, the subject, makes a forceful expiration through the mouthpiece., Alveolar air is expired at the end of forced expiration. So,, by using the three-way cock, the last portion of expired, air (alveolar air) is collected in the sampling tube., , EXPIRED AIR, , Alveolar air is constantly renewed. Rate of renewal is, slow during normal breathing. During each breath, out, of 500 mL of tidal volume only 350 mL of air enters, the alveoli and the remaining quantity of 150 mL (30%), becomes dead space air. Hence, the amount of alveolar, air replaced by new atmospheric air with each breath is, only about 70% of the total alveolar air., Thus,, Alveolar air =, , METHOD OF COLLECTION, , 350, , × 100 = 70%, , 500, Slow renewal of alveolar air is responsible for, prevention of sudden changes in concentration of gases, in the blood., , DEFINITION, Expired air is the amount of air that is exhaled during, expiration. It is a combination of dead space air and, alveolar air., COMPOSITION, Concentration of gases in expired air is somewhere, between inspired air and alveolar air. Composition of, expired air is given in Table 123.1 along with composition, of inspired air and alveolar air., METHOD OF COLLECTION, Expired air is collected by using Douglas bag.
Page 727 :
Exchange of, Respiratory Gases, , Chapter, , 124, , INTRODUCTION, EXCHANGE OF RESPIRATORY GASES IN LUNGS, , , , , , , RESPIRATORY MEMBRANE, DIFFUSING CAPACITY, DIFFUSION COEFFICIENT AND FICK LAW OF DIFFUSION, DIFFUSION OF OXYGEN, DIFFUSION OF CARBON DIOXIDE, , EXCHANGE OF RESPIRATORY GASES AT TISSUE LEVEL, , , , DIFFUSION OF OXYGEN FROM BLOOD INTO THE TISSUES, DIFFUSION OF CARBON DIOXIDE FROM TISSUES INTO THE BLOOD, , RESPIRATORY EXCHANGE RATIO, , , , DEFINITION, NORMAL VALUES, , RESPIRATORY QUOTIENT, , , , DEFINITION, NORMAL VALUE, , INTRODUCTION, , RESPIRATORY MEMBRANE, , Oxygen is essential for the cells. Carbon dioxide,, which is produced as waste product in the cells must, be expelled from the cells and body. Lungs serve to, exchange these two gases with blood., , Respiratory membrance is a membranous structure, through which exchange of respiratory gases takes, place. It is formed by epithelium of respiratory unit, and endothelium of pulmonary capillary. Epithelium, of respiratory unit is a very thin layer (Chapter 118)., Since, the capillaries are in close contact with this, membrane, alveolar air is in close proximity to capillary, blood. This facilitates gaseous exchange between air, and blood (Fig. 124.1)., Respiratory membrane is formed by different layers, of structures belonging to the alveoli and capillaries., , EXCHANGE OF RESPIRATORY, GASES IN LUNGS, In the lungs, exchange of respiratory gases takes place, between the alveoli of lungs and the blood. Oxygen, enters the blood from alveoli and carbon dioxide is, expelled out of blood into alveoli. Exchange occurs, through bulk flow diffusion (Chapter 3)., Exchange of gases between blood and alveoli, takes place through respiratory membrane. Refer, Chapter 118 for details., , Layers of Respiratory Membrane, Different layers of respiratory membrane from within, outside are given in Table 124.1., In spite of having many layers, respiratory membrane, is very thin with an average thickness of 0.5 μ. Total
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706 Section 9 t Respiratory System and Environmental Physiology, surface area of the respiratory membrane in both the, lungs is about 70 square meter., Average diameter of pulmonary capillary is only, 8 µ, which means that the RBCs with a diameter of, 7.4 µ actually squeeze through the capillaries. Therefore,, the membrane of RBCs is in close contact with capillary, wall. This facilitates quick exchange of oxygen and car, bon dioxide between the blood and alveoli., DIFFUSING CAPACITY, Diffusing capacity is defined as the volume of gas, that diffuses through the respiratory membrane each, minute for a pressure gradient of 1 mm Hg., TABLE 124.1: Layers of respiratory membrane, Portion, , Alveolar portion, , Layers, 1. Monomolecular layer, of surfactant, which, spreads over the surface, of alveoli, 2. Thin fluid layer that lines, the alveoli, 3. Alveolar epithelial layer,, which is composed, of thin epithelial cells, resting on a basement, membrane, , Between alveolar and, capillary portions, , 4. An interstitial space, , Capillary portion, , 5. Basement membrane of, capillary, 6. Capillary endothelial, cells, , Diffusing Capacity for Oxygen, and Carbon Dioxide, Diffusing capacity for oxygen is 21 mL/minute/1 mm Hg., Diffusing capacity for carbon dioxide is 400 mL/minute/1, mm Hg. Thus, the diffusing capacity for carbon dioxide, is about 20 times more than that of oxygen., Factors Affecting Diffusing Capacity, 1. Pressure gradient, Diffusing capacity is directly proportional to pressure, gradient. Pressure gradient is the difference between, the partial pressure of a gas in alveoli and pulmonary, capillary blood (see below). It is the major factor, which, affects the diffusing capacity., 2. Solubility of gas in fluid medium, Diffusing capacity is directly proportional to solubility, of the gas. If the solubility of a gas is more in the fluid, medium, a large number of molecules dissolve in it and, diffuse easily., 3. Total surface area of respiratory membrane, Diffusing capacity is directly proportional to surface area, of respiratory membrane. Surface area of respiratory, membrane in each lung is about 70 sq m. If the total, surface area of respiratory membrane decreases, the, diffusing capacity for the gases is decreased. Diffusing, capacity is decreased in emphysema in which many of, the alveoli are collapsed because of heavy smoking or, oxidant gases., 4. Molecular weight of the gas, Diffusing capacity is inversely proportional to molecular, weight of the gas. If the molecular weight is more, the, density is more and the rate of diffusion is less., 5. Thickness of respiratory membrane, Diffusion is inversely proportional to the thickness, of respiratory membrane. More the thickness of res, piratory membrane less is the diffusion. It is because, the distance through which the diffusion takes place is, long. In conditions like fibrosis and edema, the diffusion, rate is reduced, because the thickness of respiratory, membrane is increased., Relation between Diffusing Capacity, and Factors Affecting it, , FIGURE 124.1: Structure of respiratory membrane, , Relation between diffusing capacity and the factors, affecting it is expressed by the following formula:
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Chapter 124 t Exchange of Respiratory Gases 707, DC ∞, DC, Pg, S, A, Mw, D, , =, =, =, =, =, =, , Pg × S × A, , Mw × D, Diffusing capacity, Pressure gradient, Solubility of gas, Surface area of respiratory membrane, Molecular weight, Thickness of respiratory membrane., , Thus,, Amount diffused = Area × Concentration gradient, × Diffusion coefficient, Formula of Fick law:, J=–D×A×, , dc, , Diffusion coefficient is defined as a constant (a factor, of proportionality), which is the measure of a substance, diffusing through the concentration gradient. It is also, known as diffusion constant. It is related to size and, shape of the molecules of the substance., , dx, Where,, J, = Amount of substance diffused, D, = Diffusion coefficient, A, = Area through which diffusion occurs, dc/dx = Concentration gradient., Negative sign in the formula indicates that diffusion, occurs from region of higher concentration to region of, lower concentration. Diffusion coefficient reduces when, the molecular size of diffusing substance is increased., It increases when the size is decreased, i.e. the smaller, molecules diffuse rapidly than the larger ones., , Fick Law of Diffusion, , DIFFUSION OF OXYGEN, , Diffusion is well described by Fick law of diffusion., According to this law, amount of a substance crossing, a given area is directly proportional to the area, available for diffusion, concentration gradient and a, constant known as diffusion coefficient., , Diffusion of Oxygen from Atmospheric, Air into Alveoli, , DIFFUSION COEFFICIENT AND, FICK LAW OF DIFFUSION, Diffusion Coefficient, , FIGURE 124.2: Diffusion of oxygen from alveolus, to pulmonary capillary, , Partial pressure of oxygen in the atmospheric air is 159, mm Hg and in the alveoli, it is 104 mm Hg. Because of, , FIGURE 124.3: Diffusion of carbon dioxide from, pulmonary capillary to alveolus
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708 Section 9 t Respiratory System and Environmental Physiology, TABLE 124.2: Partial pressure and content of oxygen and carbon dioxide in alveoli, capillaries and tissue, Arterial end, of pulmonary, capillary, , Alveoli, , Venous end, of pulmonary, capillary, , Arterial end, of systemic, capillary, , Tissue, , Venous end, of systemic, capillary, , pO2 (mm Hg), , 40, , 104, , 104, , 95, , 40, , 40, , Gas, , Oxygen content (mL%), , 14, , –, , 19, , 19, , –, , 14, , pCO2 (mm Hg), , 46, , 40, , 40, , 40, , 46, , 46, , Carbon dioxide content (mL%), , 52, , –, , 48, , 48, , –, , 52, , the pressure gradient of 55 mm Hg, oxygen easily enters, from atmospheric air into the alveoli (Table 124.2)., , of 6 mm Hg is responsible for the diffusion of carbon, dioxide from blood into the alveoli (Fig. 124.3)., , Diffusion of Oxygen from Alveoli into Blood, , Diffusion of Carbon Dioxide from Alveoli, into Atmospheric Air, , When blood passes through pulmonary capillary, RBC is, exposed to oxygen only for 0.75 second at rest and only, for 0.25 second during severe exercise. So, diffusion of, oxygen must be quicker and effective. Fortunately, this, is possible because of pressure gradient., Partial pressure of oxygen in the pulmonary capi, llary is 40 mm Hg and in the alveoli, it is 104 mm Hg., Pressure gradient is 64 mm Hg. It facilitates the diffusion, of oxygen from alveoli into the blood (Fig. 124.2)., , In atmospheric air, partial pressure of carbon dioxide is, very insignificant and is only about 0.3 mm Hg whereas,, in the alveoli, it is 40 mm Hg. So, carbon dioxide enters, passes to atmosphere from alveoli easily., , EXCHANGE OF RESPIRATORY, GASES AT TISSUE LEVEL, , DIFFUSION OF CARBON DIOXIDE, , Oxygen enters the cells of tissues from blood and, carbon dioxide is expelled from cells into the blood., , Diffusion of Carbon Dioxide from, Blood into Alveoli, , DIFFUSION OF OXYGEN FROM, BLOOD INTO THE TISSUES, , Partial pressure of carbon dioxide in alveoli is 40 mm Hg, whereas in the blood it is 46 mm Hg. Pressure gradient, , Partial pressure of oxygen in venous end of pulmonary, capillary is 104 mm Hg. However, partial pressure of, , FIGURE 124.4: Diffusion of oxygen from capillary to tissue, , FIGURE 124.5: Diffusion of carbon dioxide, from tissue to capillary
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Chapter 124 t Exchange of Respiratory Gases 709, oxygen in the arterial end of systemic capillary is only, 95 mm Hg. It may be because of physiological shunt in, lungs. Due to venous admixture in the shunt (Chapter, 119), 2% of blood reaches the heart without being, oxygenated., Average oxygen tension in the tissues is 40 mm, Hg. It is because of continuous metabolic activity, and constant utilization of oxygen. Thus, a pressure, gradient of about 55 mm Hg exists between capillary, blood and the tissues so that oxygen can easily diffuse, into the tissues (Fig. 124.4)., Oxygen content in arterial blood is 19 mL% and in, the venous blood, it is 14 mL%. Thus, the diffusion of, oxygen from blood to tissues is 5 mL/100 mL of blood., , DIFFUSION OF CARBON DIOXIDE, FROM TISSUES INTO THE BLOOD, Due to continuous metabolic activity, carbon dioxide, is produced constantly in the cells of tissues. So, the, partial pressure of carbon dioxide is high in the cells and, is about 46 mm Hg. Partial pressure of carbon dioxide, in arterial blood is 40 mm Hg. Pressure gradient of 6, mm Hg is responsible for the diffusion of carbon dioxide, from tissues to the blood (Figs. 124.5 and 124.6)., Carbon dioxide content in arterial blood is 48 mL%., And in the venous blood, it is 52 mL%. So, the diffusion, of carbon dioxide from tissues to blood is 4 mL/100 mL, of blood (Fig. 124.5)., , FIGURE 124.6: Partial pressure and content of oxygen and carbon dioxide in blood, alveoli and tissues
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710 Section 9 t Respiratory System and Environmental Physiology, , RESPIRATORY EXCHANGE RATIO, DEFINITION, Respiratory exchange ratio (R) is the ratio between the, net output of carbon dioxide from tissues to simultaneous, net uptake of oxygen by the tissues., R =, , CO2 output, O2 uptake, , the R is about 0.825. In steady conditions, respiratory, exchange ratio is equal to respiratory quotient., , RESPIRATORY QUOTIENT, DEFINITION, Respiratory quotient is the molar ratio of carbon di, oxide production to oxygen consumption. It is used to, determine the utilization of different foodstuffs., , NORMAL VALUES, , NORMAL VALUE, , Value of R depends upon the type of food substance, that is metabolized., When a person utilizes only carbohydrates for meta, bolism, R is 1.0. That means during carbohydrate, metabolism, the amount of carbon dioxide produced in, the tissue is equal to the amount of oxygen consumed., If only fat is used for metabolism, the R is 0.7. When, fat is utilized, oxygen reacts with fats and a large portion, of oxygen combines with hydrogen ions to form water, instead of carbon dioxide. So, the carbon dioxide output, is less than the oxygen consumed. And the R is less., If only protein is utilized, R is 0.803., However, when a balanced diet containing average, quantity of proteins, carbohydrates and lipids is utilized,, , For about 1 hour after meals the respiratory quotient, is 1.0. It is because usually, immediately after taking, meals, only the carbohydrates are utilized by the tissues., During the metabolism of carbohydrates, one molecule, of carbon dioxide is produced for every molecule of, oxygen consumed by the tissues. Respiratory quotient, is 1.0, which is equal to respiratory exchange ratio., After utilization of all the carbohydrates available,, body starts utilizing fats. Now the respiratory quotient, becomes 0.7. When the proteins are metabolized, it, becomes 0.8., During exercise, the respiratory quotient increases, (Chapter 132).
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Transport of, Respiratory Gases, , Chapter, , 125, , INTRODUCTION, TRANSPORT OF OXYGEN, , , , , AS SIMPLE SOLUTION, IN COMBINATION WITH HEMOGLOBIN, OXYGEN-HEMOGLOBIN DISSOCIATION CURVE, , TRANSPORT OF CARBON DIOXIDE, , , , , , , AS DISSOLVED FORM, AS CARBONIC ACID, AS BICARBONATE, AS CARBAMINO COMPOUNDS, CARBON DIOXIDE DISSOCIATION CURVE, , INTRODUCTION, , AS SIMPLE SOLUTION, , Blood serves to transport the respiratory gases. Oxygen,, which is essential for the cells is transported from alveoli, of lungs to the cells. Carbon dioxide, which is the waste, product in cells is transported from cells to lungs., , Oxygen dissolves in water of plasma and is transported, in this physical form. Amount of oxygen transported in, this way is very negligible. It is only 0.3 mL/100 mL, of plasma. It forms only about 3% of total oxygen in, blood. It is because of poor solubility of oxygen in, water content of plasma. Still, transport of oxygen in, this form becomes important during the conditions, like muscular exercise to meet the excess demand of, oxygen by the tissues., , TRANSPORT OF OXYGEN, Oxygen is transported from alveoli to the tissue by, blood in two forms:, 1. As simple physical solution, 2. In combination with hemoglobin., Partial pressure and content of oxygen in arterial, blood and venous blood are given in Table 125.1., TABLE 125.1: Gases in arterial and venous blood, Arterial, blood, , Venous, blood, , Partial pressure (mm Hg), , 95, , 40, , Content (mL%), , 19, , 14, , Partial pressure (mm Hg), , 40, , 46, , Content (mL%), , 48, , 52, , Gas, Oxygen, Carbon, dioxide, , IN COMBINATION WITH HEMOGLOBIN, Oxygen combines with hemoglobin in blood and is, transported as oxyhemoglobin. Transport of oxygen, in this form is important because, maximum amount, (97%) of oxygen is transported by this method., Oxygenation of Hemoglobin, Oxygen combines with hemoglobin only as a physical combination. It is only oxygenation and not, oxida tion. This type of combination of oxygen with, hemoglobin has got some advantages. Oxygen can be, readily released from hemoglobin when it is needed.
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712 Section 9 t Respiratory System and Environmental Physiology, Hemoglobin accepts oxygen readily whenever the partial, pressure of oxygen in the blood is more. Hemoglobin, gives out oxygen whenever the partial pressure of, oxygen in the blood is less., Oxygen combines with the iron in heme part of, hemoglobin. Each molecule of hemoglobin contains 4, atoms of iron. Iron of the hemoglobin is present in ferrous, form. Each iron atom combines with one molecule of, oxygen. After combination, iron remains in ferrous, form only. That is why the combination of oxygen with, hemoglobin is called oxygenation and not oxidation., Oxygen Carrying Capacity of Hemoglobin, Oxygen carrying capacity of hemoglobin is the amount, of oxygen transported by 1 gram of hemoglobin. It is, 1.34 mL/g., , hemoglobin accepts oxygen and when the partial pressure of oxygen is less, hemoglobin releases oxygen., Method to Plot Oxygen-hemoglobin, Dissociation Curve, Ten flasks or tonometers are taken. Each one is, filled with a known quantity of blood with known, concentration of hemoglobin. Blood in each tonometer, is exposed to oxygen at different partial pressures., Tonometer is rotated at a constant temperature till the, blood takes as much of oxygen as it can. Then, blood, is analyzed to measure the percentage saturation of, hemoglobin with oxygen. Partial pressure of oxygen, and saturation of hemoglobin are plotted to obtain the, oxygen-hemoglobin dissociation curve., Normal Oxygen-hemoglobin Dissociation Curve, , Oxygen Carrying Capacity of Blood, Oxygen carrying capacity of blood refers to the amount, of oxygen transported by blood. Normal hemoglobin, content in blood is 15 g%., Since oxygen carrying capacity of hemoglobin is, 1.34 mL/g, blood with 15 g% of hemoglobin should carry, 20.1 mL% of oxygen, i.e. 20.1 mL of oxygen in 100 mL, of blood., But, blood with 15 g% of hemoglobin carries only 19, mL% of oxygen, i.e. 19 mL of oxygen is carried by 100, mL of blood (Table 125.1). Oxygen carrying capacity of, blood is only 19 mL% because the hemoglobin is not, fully saturated with oxygen. It is saturated only for about, 95%., , Under normal conditions, oxygen-hemoglobin dissociation curve is ‘S’ shaped or sigmoid shaped (Fig.125.1)., Lower part of the curve indicates dissociation of oxygen, from hemoglobin. Upper part of the curve indicates, the uptake of oxygen by hemoglobin depending upon, partial pressure of oxygen., P50, P50 is the partial pressure of oxygen at which hemoglobin, saturation with oxygen is 50%. When the partial pressure of oxygen is 25 to 27 mm Hg, the hemoglobin is, , Saturation of Hemoglobin with Oxygen, Saturation is the state or condition when hemoglobin, is unable to hold or carry any more oxygen. Saturation, of hemoglobin with oxygen depends upon partial, pressure of oxygen. And it is explained by oxygenhemoglobin dissociation curve., OXYGEN-HEMOGLOBIN, DISSOCIATION CURVE, Oxygen-hemoglobin dissociation curve is the curve, that demonstrates the relationship between partial, pressure of oxygen and the percentage saturation, of hemoglobin with oxygen. It explains hemoglobin’s, affinity for oxygen., Normally in the blood, hemoglobin is saturated, with oxygen only up to 95%. Saturation of hemoglobin, with oxygen depends upon the partial pressure of, oxygen. When the partial pressure of oxygen is more,, , FIGURE 125.1: Oxygen-hemoglobin dissociation curve
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Chapter 125 t Transport of Respiratory Gases 713, saturated to about 50%. That is, the blood contains 50%, of oxygen. At 40 mm Hg of partial pressure of oxygen,, the saturation is 75%. It becomes 95% when the partial, pressure of oxygen is 100 mm Hg., Factors Affecting Oxygen-hemoglobin, Dissociation Curve, Oxygen-hemoglobin dissociation curve is shifted to left, or right by various factors:, 1. Shift to left indicates acceptance (association) of, oxygen by hemoglobin, 2. Shift to right indicates dissociation of oxygen from, hemoglobin., 1. Shift to right, Oxygen-hemoglobin dissociation curve is shifted to, right in the following conditions:, i. Decrease in partial pressure of oxygen, ii. Increase in partial pressure of carbon dioxide, (Bohr effect), iii. Increase in hydrogen ion concentration and, decrease in pH (acidity), iv. Increased body temperature, v. Excess of 2,3-diphosphoglycerate (DPG) in, RBC. It is also called 2,3-biphosphoglycerate, (BPG). DPG is a byproduct in Embden-Meyerhof pathway of carbohydrate metabolism. It, combines with β-chains of hemoglobin. In conditions like muscular exercise and in high attitude,, the DPG increases in RBC. So, the oxygenhemoglobin dissociation curve shifts to right to, a great extent., , Due to this pressure gradient, carbon dioxide, enters the blood and oxygen is released from the blood, to the tissues. Presence of carbon dioxide decreases, the affinity of hemoglobin for oxygen. It enhances, further release of oxygen to the tissues and oxygendissociation curve is shifted to right., Factors influencing Bohr effect, All the factors, which shift the oxygen-dissociation curve, to right (mentioned above) enhance the Bohr effect., , TRANSPORT OF CARBON DIOXIDE, Carbon dioxide is transported by the blood from cells, to the alveoli., Carbon dioxide is transported in the blood in four, ways:, 1. As dissolved form (7%), 2. As carbonic acid (negligible), 3. As bicarbonate (63%), 4. As carbamino compounds (30%)., AS DISSOLVED FORM, Carbon dioxide diffuses into blood and dissolves in the, fluid of plasma forming a simple solution. Only about, 3 mL/100 mL of plasma of carbon dioxide is transported, as dissolved state. It is about 7% of total carbon, dioxide in the blood., AS CARBONIC ACID, Part of dissolved carbon dioxide in plasma combines, with the water to form carbonic acid. Transport of, carbon dioxide in this form is negligible., , 2. Shift to left, , AS BICARBONATE, , Oxygen-hemoglobin dissociation curve is shifted to, left in the following conditions:, i. In fetal blood because, fetal hemoglobin has, got more affinity for oxygen than the adult, hemoglobin, ii. Decrease in hydrogen ion concentration and, increase in pH (alkalinity)., , About 63% of carbon dioxide is transported as bicarbonate. From plasma, carbon dioxide enters the, RBCs. In the RBCs, carbon dioxide combines with, water to form carbonic acid. The reaction inside RBCs, is very rapid because of the presence of carbonic, anhydrase. This enzyme accelerates the reaction., Carbonic anhydrase is present only inside the RBCs, and not in plasma. That is why carbonic acid formation, is at least 200 to 300 times more in RBCs than in, plasma., Carbonic acid is very unstable. Almost all carbonic, acid (99.9%) formed in red blood corpuscles, dissociates, into bicarbonate and hydrogen ions. Concentration of, bicarbonate ions in the cell increases more and more., Due to high concentration, bicarbonate ions diffuse, through the cell membrane into plasma., , Bohr Effect, Bohr effect is the effect by which presence of carbon, dioxide decreases the affinity of hemoglobin for oxygen., Bohr effect was postulated by Christian Bohr in 1904., In the tissues, due to continuous metabolic activities,, the partial pressure of carbon dioxide is very high and, the partial pressure of oxygen is low.
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714 Section 9 t Respiratory System and Environmental Physiology, Chloride Shift or Hamburger Phenomenon, Chloride shift or Hamburger phenomenon is the exchange of a chloride ion for a bicarbonate ion across, RBC membrane. It was discovered by Hartog Jakob, Hamburger in 1892., Chloride shift occurs when carbon dioxide enters the, blood from tissues. In plasma, plenty of sodium chloride, is present. It dissociates into sodium and chloride ions, (Fig. 125.2). When the negatively charged bicarbonate, ions move out of RBC into the plasma, the negatively, charged chloride ions move into the RBC in order to, maintain the electrolyte equilibrium (ionic balance)., Anion exchanger 1 (band 3 protein), which acts, like antiport pump in RBC membrane is responsible, for the exchange of bicarbonate ions and chloride, ions. Bicarbonate ions combine with sodium ions in, the plasma and form sodium bicarbonate. In this form,, it is transported in the blood., Hydrogen ions dissociated from carbonic acid are, buffered by hemoglobin inside the cell., Reverse Chloride Shift, Reverse chloride shift is the process by which chloride, ions are moved back into plasma from RBC shift. It, occurs in lungs. It helps in elimination of carbon, dioxide from the blood. Bicarbonate is converted back, into carbon dioxide, which has to be expelled out. It, takes place by the following mechanism:, , When blood reaches the alveoli, sodium bicarbonate in plasma dissociates into sodium and bicarbonate, ions. Bicarbonate ion moves into the RBC. It makes, chloride ion to move out of the RBC into the plasma, where, it combines with sodium and forms sodium chloride., Bicarbonate ion inside the RBC combines with, hydrogen ion forms carbonic acid, which dissociates, into water and carbon dioxide. Carbon dioxide is then, expelled out., AS CARBAMINO COMPOUNDS, About 30% of carbon dioxide is transported as carbamino compounds. Carbon dioxide is transported in, blood in combination with hemoglobin and plasma, proteins. Carbon dioxide combines with hemoglobin to, form carbamino hemoglobin or carbhemoglobin. And, it combines with plasma proteins to form carbamino, proteins. Carbamino hemoglobin and carbamino, proteins are together called carbamino compounds., Carbon dioxide combines with proteins or hemoglobin with a loose bond so that, carbon dioxide is, easily released into alveoli, where the partial pressure, of carbon dioxide is low. Thus, the combination of, carbon dioxide with proteins and hemoglobin is a, reversible one. Amount of carbon dioxide transported, in combination with plasma proteins is very less compared to the amount transported in combination with, hemoglobin. It is because the quantity of proteins in, plasma is only half of the quantity of hemoglobin., , FIGURE 125.2: Transport of carbon dioxide in blood in the form of bicarbonate and chloride shift
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Chapter 125 t Transport of Respiratory Gases 715, CARBON DIOXIDE DISSOCIATION CURVE, Carbon dioxide is transported in blood as physical, solution and in combination with water, plasma, proteins and hemoglobin. The amount of carbon, dioxide combining with blood depends upon the partial, pressure of carbon dioxide., Carbon dioxide dissociation curve is the curve, that demonstrates the relationship between the partial, pressure of carbon dioxide and the quantity of carbon, dioxide that combines with blood., Normal Carbon Dioxide Dissociation Curve, Normal carbon dioxide dissociation curve shows that, the carbon dioxide content in the blood is 48 mL%, when the partial pressure of carbon dioxide is 40, mm Hg and it is 52 mL% when the partial pressure of, carbon dioxide is 48 mm Hg. Carbon dioxide content, becomes 70 mL% when the partial pressure is about, 100 mm Hg (Fig. 125.3)., Haldane Effect, Haldane effect is the effect by which combination of, oxygen with hemoglobin displaces carbon dioxide from, hemoglobin. It was first described by John Scott Haldane, in 1860. Excess of oxygen content in blood causes shift, of the carbon dioxide dissociation curve to right., Causes for Haldane effect, Due to the combination with oxygen, hemoglobin becomes strongly acidic. It causes displacement of carbon dioxide from hemoglobin in two ways:, , FIGURE 125.3: Carbon dioxide dissociation curve, , 1. Highly acidic hemoglobin has low tendency to, combine with carbon dioxide. So, carbon dioxide is, displaced from blood., 2. Because of the acidity, hydrogen ions are released, in excess. Hydrogen ions bind with bicarbonate, ions to form carbonic acid. Carbonic acid in turn, dissociates into water and carbon dioxide. Carbon, dioxide is released from blood into alveoli., Significance of Haldane effect, Haldane effect is essential for:, 1. Release of carbon dioxide from blood into the, alveoli of lungs, 2. Uptake of oxygen by the blood.
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Regulation of Respiration, , Chapter, , 126, , INTRODUCTION, NERVOUS MECHANISM, , , , , , , , RESPIRATORY CENTERS, MEDULLARY CENTERS, PONTINE CENTERS, CONNECTIONS OF RESPIRATORY CENTERS, INTEGRATION OF RESPIRATORY CENTERS, FACTORS AFFECTING RESPIRATORY CENTERS, , CHEMICAL MECHANISM, , , , CENTRAL CHEMORECEPTORS, PERIPHERAL CHEMORECEPTORS, , INTRODUCTION, , RESPIRATORY CENTERS, , Respiration is a reflex process. But it can be controlled, voluntarily for a short period of about 40 seconds., However, by practice, breathing can be withheld for, a long period. At the end of that period, the person is, forced to breathe., Respiration is subjected to variation, even under, normal physiological conditions. For example, emotion, and exercise increase the rate and force of respiration. But the altered pattern of respiration is brought, back to normal, within a short time by some regulatory, mechanisms in the body., Normally, quiet regular breathing occurs because, of two regulatory mechanisms:, 1. Nervous or neural mechanism, 2. Chemical mechanism., , Respiratory centers are group of neurons, which, control the rate, rhythm and force of respiration. These, centers are bilaterally situated in reticular formation, of the brainstem (Fig. 126.1). Depending upon the, situation in brainstem, the respiratory centers are, classified into two groups:, A. Medullary centers consisting of, 1. Dorsal respiratory group of neurons, 2. Ventral respiratory group of neurons, B. Pontine centers, 3. Apneustic center, 4. Pneumotaxic center., , NERVOUS MECHANISM, , Situation, , Nervous mechanism that regulates the respiration, includes:, 1. Respiratory centers, 2. Afferent nerves, 3. Efferent nerves., , Dorsal respiratory group of neurons are diffusely, situated in the nucleus of tractus solitarius which is, present in the upper part of the medulla oblongata (Fig., 126.1). Usually, these neurons are collectively called, , MEDULLARY CENTERS, 1. Dorsal Respiratory Group of Neurons, , inspiratory center.
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Chapter 126 t Regulation of Respiration 717, 2. Ventral Respiratory Group of Neurons, Situation, Ventral respiratory group of neurons are present in, nucleus ambiguous and nucleus retroambiguous., These two nuclei are situated in the medulla oblongata,, anterior and lateral to the nucleus of tractus solitarius., Earlier, the ventral group neurons were collectively, called expiratory center., Ventral respiratory group has both inspiratory and, expiratory neurons. Inspiratory neurons are found in, the central area of the group. Expiratory neurons are, in the caudal and rostral areas of the group., Function, Normally, ventral group neurons are inactive during, quiet breathing and become active during forced breathing. During forced breathing, these neurons stimulate, both inspiratory muscles and expiratory muscles., Experimental evidence, Electrical stimulation of the inspiratory neurons in, ventral group causes contraction of inspiratory muscles, and prolonged inspiration. Stimulation of expiratory, neurons causes contraction of expiratory muscles and, prolonged expiration., FIGURE 126.1: Nervous regulation of respiration., Solid green line = Stimulation, Dotted red line = Inhibition., , PONTINE CENTERS, 3. Apneustic Center, , All the neurons of dorsal respiratory group are, inspiratory neurons and generate inspiratory ramp by, the virtue of their autorhythmic property (Table 126.1)., , Function, Dorsal group of neurons are responsible for basic, rhythm of respiration (see below for details)., Experimental evidence, Electrical stimulation of these neurons in animals by, using needle electrode causes contraction of inspiratory muscles and prolonged inspiration., , Situation, Apneustic center is situated in the reticular formation of, lower pons., Function, Apneustic center increases depth of inspiration by, acting directly on dorsal group neurons., Experimental evidence, Stimulation of apneustic center causes apneusis., Apneusis is an abnormal pattern of respiration, charac-, , TABLE 126.1: Medullary centers, Features, , Dorsal group, , Ventral group, , Situation, , Diffusely situated in nucleus of tractus solitarius In nucleus ambiguous and nucleus retroambiguous, , Type of neurons, , Inspiratory neurons, , Inspiratory and expiratory neurons, , Function, , Always active, Generate inspiratory ramp, Has autorhythmic property, , Inactive during quiet breathing, Active during forced breathing
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718 Section 9 t Respiratory System and Environmental Physiology, terized by prolonged inspiration followed by short,, inefficient expiration., 4. Pneumotaxic Center, , 2. Stretch receptors of lungs via vagus nerve., By receiving afferent impulses from these receptors, respiratory centers modulate the movements of, thoracic cage and lungs through efferent nerve fibers., , Situation, , INTEGRATION OF RESPIRATORY CENTERS, , Pneumotaxic center is situated in the dorsolateral part, of reticular formation in upper pons. It is formed by, neurons of medial parabrachial and subparabrachial, nuclei. Subparabrachial nucleus is also called ventral, parabrachial or Kölliker-Fuse nucleus., Function, Primary function of pneumotaxic center is to control, the medullary respiratory centers, particularly the, dorsal group neurons. It acts through apneustic center., Pneumotaxic center inhibits the apneustic center so, that the dorsal group neurons are inhibited. Because, of this, inspiration stops and expiration starts. Thus,, pneumotaxic center influences the switching between, inspiration and expiration., Pneumotaxic center increases respiratory rate by, reducing the duration of inspiration., , Role of Medullary Centers, Rhythmic discharge of inspiratory impulses, Dorsal respiratory group of neurons are responsible, for the normal rhythm of respiration. These neurons, maintain the normal rhythm of respiration by discharging, impulses (action potentials) rhythmically. These, impulses are transmitted to respiratory muscles by, phrenic and intercostal nerves., Inspiratory ramp, Inspiratory ramp is the pattern of impulse discharge, from dorsal respiratory group of neurons. These impulses are characterized by steady increase in amplitude of the action potential. Impulse discharge from, these neurons is not sudden and it is also not uniform., , Experimental evidence, , Inspiratory ramp signals, , Stimulation of pneumotaxic center does not produce, any typical effect, except slight prolongation of, expiration, by inhibiting the dorsal respiratory group, of neurons through apneustic center. Destruction or, inactivation of pneumotaxic center results in apneusis., , To start with, the amplitude of action potential is low. It, is due to the activation of only few neurons. Later, more, and more neurons are activated, leading to gradual, increase in the amplitude of action potential in a ramp, fashion. Impulses of this type discharged from dorsal, group of neurons are called inspiratory ramp signals., Ramp signals are not produced continuously but, only for a period of 2 seconds, during which inspiration, occurs. After 2 seconds, ramp signals stop abruptly, and do not appear for another 3 seconds. Switching, off the ramp signals causes expiration. At the end of, 3 seconds, inspriatory ramp signals reappear in the, same pattern and the cycle is repeated., Normally, during inspiration, dorsal respiratory, group neurons inhibit expiratory neurons of ventral, group. During expiration, the expiratory neurons, inhibit the dorsal group neurons. Thus, the medullary, respiratory centers control each other., , CONNECTIONS OF RESPIRATORY CENTERS, Efferent Pathway, Nerve fibers from respiratory centers leave the brain, stem and descend in anterior part of lateral columns of, spinal cord., These nerve fibers terminate on motor neurons, in the anterior horn cells of cervical and thoracic, segments of spinal cord. From motor neurons of spinal, cord, two sets of nerve fibers arise:, 1. Phrenic nerve fibers (C3 to C5), which supply the, diaphragm, 2. Intercostal nerve fibers (T1 to T11), which supply, the external intercostal muscles., Vagus nerve also contains some efferent fibers, from the respiratory centers., , Significance of inspiratory ramp signals, Significance of inspiratory ramp signals is that there is, a slow and steady inspiration, so that the filling of lungs, with air is also steady., , Afferent Pathway, Respiratory centers receive afferent impulses from:, 1. Peripheral chemoreceptors and baroreceptors via, branches of glossopharyngeal and vagus nerves, , Role of Pontine Centers, Pontine respiratory centers regulate the medullary, centers. Apneustic center accelerates the activity of
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Chapter 126 t Regulation of Respiration 719, dorsal group of neurons and the stimulation of this, center causes prolonged inspiration., Pneumotaxic center inhibits the apneustic center, and restricts the duration of inspiration., Pre-Bötzinger Complex, Pre-Bötzinger complex (pre-BötC) is an additional, respiratory center found in animals. It is formed by a, group of neurons called pacemaker neurons, located in, the ventrolateral part of medulla. Pacemaker neurons, generate the rhythmic respiratory impulses. Medullary, centers send nerve fibers into this complex. Exact, functioning mechanism of this complex is not known., FACTORS AFFECTING, RESPIRATORY CENTERS, Respiratory centers regulate the respiratory movements, by receiving impulses from various sources in the body., , FIGURE 126.2: HeringBreuer inflation reflex. DGN = Dorsal, respiratory group of neurons. Dashed red arrow indicates, inhibition., , 1. Impulses from Higher Centers, Higher centers alter the respiration by sending impulses, directly to dorsal group of neurons. Impulses from, anterior cingulate gyrus, genu of corpus callosum,, olfactory tubercle and posterior orbital gyrus of cerebral, cortex inhibit respiration. Impulses from motor area and, Sylvian area of cerebral cortex cause forced breathing., , limits the overstretching of lung tissues. Reverse of this, reflex is called Hering-Breuer deflation reflex and it, takes place during expiration. During expiration, as the, stretching of lungs is absent, deflation occurs., , 2. Impulses from Stretch Receptors of Lungs:, Hering-Breuer Reflex, , ‘J’ receptors are juxtacapillary receptors which are, present on the wall of the alveoli and have close contact, with the pulmonary capillaries. AS Paintal discovered, that these receptors are the sensory nerve endings, of vagus. Nerve fibers from these receptors are non, myelinated and belong to C type. Few receptors are, found on the wall of the bronchi., , HeringBreuer reflex is a protective reflex that restricts, inspiration and prevents overstretching of lung tissues., It is initiated by the stimulation of stretch receptors of, air passage., Stretch receptors are the receptors which give, response to stretch of the tissues. These receptors are, situated on the wall of the bronchi and bronchioles., Expansion of lungs during inspiration stimulates, the stretch receptors. Impulses from stretch receptors, reach the dorsal group neurons via vagal afferent fibers, and inhibit them. So, inspiration stops and expiration, starts (Fig. 126.2). Thus, the overstretching of lung, tissues is prevented., However, HeringBreuer reflex does not operate, during quiet breathing. It operates, only when the tidal, volume increases beyond 1,000 mL., , 3. Impulses from ‘J’ Receptors of Lungs, , Conditions when ‘J’ receptors are stimulated, i., ii., iii., iv., v., vi., , Pulmonary congestion, Pulmonary edema, Pneumonia, Over inflation of lungs, Microembolism in pulmonary capillaries, Stimulation by exogenous and endogenous chemical substances such as histamine, halothane,, bradykinin, serotonin and phenyldiguanide., , Hering-Breuer inflation reflex and deflation reflex, , Effect of stimulation of ‘J’ receptors, , The above mentioned reflex is called Hering-Breuer, inflation reflex since it restricts the inspiration and, , Stimulation of the ‘J’ receptors produces a reflex, response, which is characterized by apnea. Apnea is
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720 Section 9 t Respiratory System and Environmental Physiology, followed by hyperventilation, bradycardia, hypotension, and weakness of skeletal muscles., Role of ‘J’ receptors in physiological conditions is, not clear. However, these receptors are responsible, for hyperventilation in patients affected by pulmonary, congestion and left heart failure., 4. Impulses from Irritant Receptors of Lungs, Besides stretch receptors, there is another type of, receptors in the bronchi and bronchioles of lungs,, called irritant receptors. Irritant receptors are stimulated by irritant chemical agents such as ammonia and, sulfur dioxide. These receptors send afferent impulses, to respiratory centers via vagal nerve fibers., Stimulation of irritant receptors produces reflex, hyperventilation along with bronchospasm. Hyperventilation along with bronchospasm prevents further, entry of harmful agents into the alveoli., , 8. Impulses from Thermoreceptors, Thermoreceptors are cutaneous receptors, which give, response to change in the environmental temperature., Thermoreceptors are of two types, namely receptors for, cold and receptors for warmth. When body is exposed, to cold or when cold water is applied over the body,, cold receptors are stimulated and send impulses to, cerebral cortex via somatic afferent nerves. Cerebral, cortex in turn, stimulates the respiratory centers and, causes hyperventilation., 9. Impulses from Pain Receptors, Pain receptors are those which give response to pain, stimulus. Whenever pain receptors are stimulated, the, impulses are sent to cerebral cortex via somatic afferent, nerves. Cerebral cortex in turn, stimulates the respiratory, centers and causes hyperventilation (Fig. 126.3)., , 5. Impulses from Baroreceptors, , CHEMICAL MECHANISM, , Baroreceptors or pressoreceptors are the receptors, which give response to change in blood pressure. Refer, Chapter 101 for details of baroreceptors., , Chemical mechanism of regulation of respiration is, operated through the chemoreceptors. Chemoreceptors, are the sensory nerve endings, which give response to, changes in chemical constituents of blood., , Function, Baroreceptors in carotid sinus and arch of aorta give, response to increase in blood pressure. Whenever, arterial blood pressure increases, baroreceptors are, activated and send inhibitory impulses to vasomotor, center in medulla oblongata. This causes decrease in, blood pressure and inhibition of respiration. However,, in physiological conditions, the role of baroreceptors in, regulation of respiration is insignificant., 6. Impulses from Chemoreceptors, Chemoreceptors play an important role in the chemical, regulation of respiration. Details of chemoreceptors, and chemical regulation of respiration are explained, later in this Chapter., 7. Impulses from Proprioceptors, Proprioceptors are the receptors which give response, to change in the position of body. These receptors are, situated in joints, tendons and muscles. Proprioceptors, are stimulated during the muscular exercise and send, impulses to brain, particularly cerebral cortex, through, somatic afferent nerves. Cerebral cortex in turn causes, hyperventilation by sending impulses to medullary respiratory centers., , Changes in Chemical Constituents of, Blood which Stimulate Chemoreceptors, 1. Hypoxia (decreased pO2), 2. Hypercapnea (increased pCO2), 3. Increased hydrogen ion concentration., Types of Chemoreceptors, Chemoreceptors are classified into two groups:, 1. Central chemoreceptors, 2. Peripheral chemoreceptors., CENTRAL CHEMORECEPTORS, Central chemoreceptors, present in the brain., , are, , the, , chemoreceptors, , Situation, Central chemoreceptors are situated in deeper part of, medulla oblongata, close to the dorsal respiratory group, of neurons. This area is known as chemosensitive, area and the neurons are called chemoreceptors., Chemoreceptors are in close contact with blood and, cerebrospinal fluid.
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Chapter 126 t Regulation of Respiration 721, , FIGURE 126.3: Factors affecting respiratory centers, , Mechanism of Action, Central chemoreceptors are connected with respiratory, centers, particularly the dorsal respiratory group of, neurons through synapses. These chemoreceptors, act slowly but effectively. Central chemoreceptors are, responsible for 70% to 80% of increased ventilation, through chemical regulatory mechanism., Main stimulant for central chemoreceptors is the, increased hydrogen ion concentration. However, if, hydrogen ion concentration increases in the blood, it, cannot stimulate the central chemoreceptors because,, the hydrogen ions from blood cannot cross the bloodbrain barrier and blood-cerebrospinal fluid barrier., On the other hand, if carbon dioxide increases in, the blood, it can easily cross the blood-brain barrier and, bloodcerebrospinal fluid barrier and enter the interstitial, fluid of brain or the cerebrospinal fluid. There, the carbon, dioxide combines with water to form carbonic acid. Since, carbonic acid is unstable, it immediately dissociates into, hydrogen ion and bicarbonate ion (Fig. 126.4)., , CO2 + H2O → H2CO3 → H+ + HCO3–, Hydrogen ions stimulate the central chemoreceptors., From chemoreceptors, the excitatory impulses are, sent to dorsal respiratory group of neurons, resulting, in increased ventilation (increased rate and force of, breathing). Because of this, excess carbon dioxide is, washed out and respiration is brought back to normal., Lack of oxygen does not have significant effect on, the central chemoreceptors, except that it generally, depresses the overall function of brain., PERIPHERAL CHEMORECEPTORS, Peripheral chemoreceptors are the chemoreceptors, present in carotid and aortic region. Refer Chapter 101, for details., Mechanism of Action, Hypoxia is the most potent stimulant for peripheral, chemoreceptors. It is because of the presence of
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722 Section 9 t Respiratory System and Environmental Physiology, , FIGURE 126.4: Chemical regulation of respiration. CSF = Cerebrospinal fluid., , oxygen sensitive potassium channels in the glomus, cells of peripheral chemoreceptors., Hypoxia causes closure of oxygen sensitive, potassium channels and prevents potassium efflux., This leads to depolarization of glomus cells (receptor, potential) and generation of action potentials in nerve, ending., These impulses pass through aortic and Hering, nerves and excite the dorsal group of neurons. Dorsal, , group of neurons in turn, send excitatory impulses to, respiratory muscles, resulting in increased ventilation., This provides enough oxygen and rectifies the lack of, oxygen., In addition to hypoxia, peripheral chemoreceptors, are also stimulated by hypercapnea and increased, hydrogen ion concentration. However, the sensitivity, of peripheral chemoreceptors to hypercapnea and, increased hydrogen ion concentration is mild.
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Chapter, , Disturbances of, Respiration, , , , , , , , , , , , , , , , , , , , , , , 127, , INTRODUCTION, APNEA, HYPERVENTILATION, HYPOVENTILATION, HYPOXIA, OXYGEN TOXICITY (POISONING), HYPERCAPNEA, HYPOCAPNEA, ASPHYXIA, DYSPNEA, PERIODIC BREATHING, CYANOSIS, CARBON MONOXIDE POISONING, ATELECTASIS, PNEUMOTHORAX, PNEUMONIA, BRONCHIAL ASTHMA, PULMONARY EDEMA, PLEURAL EFFUSION, PULMONARY TUBERCULOSIS, EMPHYSEMA, , INTRODUCTION, Normal respiratory pattern is called eupnea. Respiratory, pattern is altered by many ways. Altered patterns of, respiration are:, 1. Tachypnea: Increase in the rate of respiration, 2. Bradypnea: Decrease in the rate of respiration, 3. Polypnea: Rapid, shallow breathing resembling, panting in dogs. In this type of breathing, only the, rate of respiration increases but the force does not, increase significantly., 4. Apnea: Temporary arrest of breathing, , 5. Hyperpnea: Increase in pulmonary ventilation due, to increase in rate or force of respiration. Increase, in rate and force of respiration occurs after exercise., It also occurs in abnormal conditions like fever or, other disorders., 6. Hyperventilation: Abnormal increase in rate and, force of respiration, which often leads to dizziness, and sometimes chest pain, 7. Hypoventilation: Decrease in rate and force of, respiration, 8. Dyspnea: Difficulty in breathing, 9. Periodic breathing: Abnormal respiratory rhythm.
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724 Section 9 t Respiratory System and Environmental Physiology, , APNEA, , 4. Vagal Apnea, , DEFINITION, , Vagal apnea is an experimental apnea, which is, produced by the stimulation of vagus nerve in animals., Stimulation of vagus nerve causes apnea by inhibiting, the inspiratory center., , Apnea is defined as the temporary arrest of breathing., Literally, apnea means absence of breathing. Apnea, can also be produced voluntarily, which is called breath, holding or voluntary apnea., APNEA TIME, , 5. Adrenaline Apnea, , CONDITIONS WHEN APNEA OCCURS, , Adrenaline apnea is the apnea that occurs after, injection of adrenaline. Administration of adrenaline, produces marked increase in arterial blood pressure., It stimulates the baroreceptors, which in turn reflexly, inhibit vasomotor center and the respiratory centers,, causing fall in blood pressure and apnea., , 1. Voluntary Effort, , CLINICAL CLASSIFICATION OF APNEA, , Breath holding time is known as apnea time. It is about, 40 to 60 seconds in a normal person, after a deep, inspiration., , Arrest of breathing by voluntary effort is known as, voluntary apnea or breath holding. Breath holding time, can be increased beyond 40 to 60 seconds by practice,, exercise, willpower and yoga., At the end of voluntary apnea, the subject is, forced to breathe, which is called the breaking point., It is because of the accumulation of carbon dioxide in, blood, which stimulates the respiratory centers. Besides, increased carbon dioxide content in blood, hypoxia, and increased hydrogen ion concentration are also, responsible for stimulation of respiratory centers. Apnea, is always followed by hyperventilation., 2. Apnea after Hyperventilation, Apnea occurs after hyperventilation. It is due to lack, of carbon dioxide. During hyperventilation, more, carbon dioxide is washed out. So, partial pressure of, carbon dioxide in the blood decreases and the number, of stimuli to the respiratory centers also decreases,, leading to apnea. During apnea, carbon dioxide, accumulates in the blood. When partial pressure of, carbon dioxide increases, the respiratory centers are, stimulated and respiration starts., 3. Deglutition Apnea, Arrest of breathing during deglutition is known as, deglutition (swallowing) apnea. It occurs reflexly during, pharyngeal stage of deglutition. When the bolus is, pushed into esophagus from pharynx during pharyngeal, stage of deglutition, there is possibility for bolus to, enter the respiratory passage through larynx, causing, serious consequences like choking. This is prevented, by deglutition apnea, during which the larynx is closed, by backward movement of epiglottis (Chapter 43)., , Clinically, apnea is classified into three types:, 1. Obstructive apnea, 2. Central apnea, 3. Mixed apnea., 1. Obstructive Apnea, Obstructive apnea occurs because of obstruction in the, respiratory tract. Respiratory tract obstruction is mainly, due to excess tissue growth like tonsils and adenoids., Common obstructive apnea is the sleep apnea., Sleep apnea, Sleep apnea is the temporary stoppage of breathing, that occurs repeatedly during sleep. It is also called, sleep disordered breathing (SDB). It commonly affects, overweight people., Major cause for sleep apnea is obstruction of upper, respiratory tract by excess tissue growth in airway, like, enlarged tonsils and large tongue., Characteristic feature of sleep apnea is loud, snoring. Snoring without sleep apnea is called simple, or primary snoring. But snoring with sleep apnea, is serious and it may become life threatening. If left, unnoticed, it may lead to hypertension, heart failure and, stroke (refer Chapter 160 for sleep apnea syndrome)., 2. Central Apnea, Central apnea occurs due to brain disorders, especially when the respiratory centers are affected. It is seen, in premature babies. Typical feature of central apnea, is a short pause in between breathing.
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Chapter 127 t Disturbances of Respiration 725, 3. Mixed Apnea, Mixed apnea is a combination of central and obstructive, apnea. It is usually seen in premature babies and in, full-term born infants. Main reason for mixed apnea is, the abnormal control of breathing due to immature or, underdeveloped brain or respiratory system., , HYPERVENTILATION, DEFINITION, Hyperventilation means increased pulmonary ventilation due to forced breathing. It is also called over, ventilation. In hyperventilation, both rate and force, of breathing are increased and a large amount of air, moves in and out of lungs. Thus, pulmonary ventilation is, increased to a great extent. Very often, hyperventilation, leads to dizziness, discomfort and chest pain., CONDITIONS WHEN, HYPERVENTILATION OCCURS, Hyperventilation mostly occurs in conditions like, exercise when partial pressure of carbon dioxide (pCO2), is increased. Excess of carbon dioxide stimulates the, respiratory centers. Voluntarily also, hyperventilation, can be produced. It is called voluntary hyperventilation., EFFECTS OF HYPERVENTILATION, During hyperventilation, excessive carbon dioxide is, washed out. In blood, the partial pressure of carbon, dioxide is reduced. It causes suppression of respiratory, centers, resulting in apnea. Apnea is followed by, Cheyne-Stokes type of periodic breathing. After a, period of Cheyne-Stokes breathing, normal respiration, is restored (Fig. 127.1)., , FIGURE 127.1: Effects of hyperventilation, , EFFECTS OF HYPOVENTILATION, Hypoventilation results in development of hypoxia along, with hypercapnea. It increases the rate and force of, respiration, leading to dyspnea. Severe conditions result, in lethargy, coma and death (Fig. 127.2)., , HYPOXIA, DEFINITION, , HYPOVENTILATION, DEFINITION, Hypoventilation is the decrease in pulmonary ventilation caused by decrease in rate or force of breathing., Thus, the amount of air moving in and out of lungs is, reduced., CONDITIONS WHEN, HYPOVENTILATION OCCURS, Hypoventilation occurs when respiratory centers are, suppressed or by administration of some drugs. It occurs, during partial paralysis of respiratory muscles also., , Hypoxia is defined as reduced availability of oxygen, to the tissues. The term anoxia refers to absence of, oxygen. In olden days, the term anoxia was in use., Since there is no possibility for total absence of oxygen, in living conditions, use of this term is abandoned., CLASSIFICATION AND CAUSES, OF HYPOXIA, Four important factors which leads to hypoxia are:, 1. Oxygen tension in arterial blood, 2. Oxygen carrying capacity of blood, 3. Velocity of blood flow, 4. Utilization of oxygen by the cells.
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726 Section 9 t Respiratory System and Environmental Physiology, iv. Cardiac disorders, in which enough blood is not, pumped to transport oxygen., i. Low oxygen tension in inspired air, Oxygen tension in inspired air is reduced in the following, conditions:, a. High altitude, b. While breathing air in closed space, c. While breathing gas mixture containing low partial, pressure of oxygen (PO2)., Because of these conditions, required quantity of, oxygen cannot enter the lungs., ii. Respiratory disorders associated with decreased, pulmonary ventilation, , FIGURE 127.2: Effects of hypoventilation, , On the basis of above factors, hypoxia is classified, into four types:, 1. Hypoxic hypoxia, 2. Anemic hypoxia, 3. Stagnant hypoxia, 4. Histotoxic hypoxia., Each type of hypoxia may be acute or chronic., Simultaneously, two or more types of hypoxia may be, present., 1. Hypoxic Hypoxia, Hypoxic hypoxia means decreased oxygen content in, blood. It is also called arterial hypoxia., Causes for hypoxic hypoxia, Hypoxic hypoxia is caused by four factors., i. Low oxygen tension in inspired (atmospheric) air,, which does not provide enough oxygen, ii. Respiratory disorders associated with decreased, pulmonary ventilation, which does not allow intake, of enough oxygen, iii. Respiratory disorders associated with inadequate, oxygenation in lungs, which does not allow diffusion, of enough oxygen, , Pulmonary ventilation decreases in the following, conditions:, a. Obstruction of respiratory passage as in asthma, b. Nervous and mechanical hindrance to respiratory, movements as in poliomyelitis, c. Depression of respiratory centers as in brain, tumors, d. Pneumothorax., In these conditions, even though enough oxygen is, available in the atmosphere, it cannot reach the lungs., iii. Respiratory disorders associated with inadequate, oxygenation of blood in lungs, Inadequate oxygenation of blood in lungs occurs in the, following conditions:, a. Impaired alveolar diffusion as in emphysema, b. Presence of non-functioning alveoli as in fibrosis, c. Filling of alveoli with fluid as in pulmonary edema,, pneumonia, pulmonary hemorrhage, d. Collapse of lungs as in bronchiolar obstruction, e. Lack of surfactant, f. Abnormal pleural cavity such as pneumothorax,, hydrothorax, hemothorax and pyothorax, g. Increased venous admixture as in the case of, bronchiectasis., In these conditions, in spite of oxygen availability, and entrance of oxygen into the alveoli, it cannot diffuse, into the blood., iv. Cardiac disorders, In congestive heart failure, oxygen availability and, diffusion are normal, but the blood cannot be pumped, from heart properly.
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Chapter 127 t Disturbances of Respiration 727, Characteristic features of hypoxic hypoxia, Hypoxic hypoxia is characterized by reduced oxygen, tension in arterial blood. All other features remain normal (Table 127.1)., , iv. Combination of hemoglobin with gases other than, oxygen and carbon dioxide, When hemoglobin combines with carbon monoxide,, hydrogen sulfide or nitrous oxide, it looses the capacity, to transport oxygen (Chapter 11)., , 2. Anemic Hypoxia, , Characteristic features of anemic hypoxia, , Anemic hypoxia is the condition characterized by the, inability of blood to carry enough amount of oxygen., Oxygen availability is normal. But the blood is not able, to take up sufficient amount of oxygen due to anemic, condition., , Anemic hypoxia is characterized by decreased oxygen, carrying capacity of blood. All other features remain, normal (Table 127.1)., , Causes for anemic hypoxia, , Stagnant hypoxia is the hypoxia caused by decreased, velocity of blood flow. It is otherwise called hypokinetic, hypoxia., , Any condition that causes anemia can cause anemic, hypoxia. It is caused by the following conditions:, i. Decreased number of RBCs, ii. Decreased hemoglobin content in the blood, iii. Formation of altered hemoglobin, iv. Combination of hemoglobin with gases other than, oxygen and carbon dioxide., i. Decreased number of RBCs, RBC decreases in conditions like bone marrow diseases,, hemorrhage, etc., ii. Decreased hemoglobin content in the blood, , 3. Stagnant Hypoxia, , Causes for stagnant hypoxia, Stagnant hypoxia occurs mainly due to reduction in, velocity of blood flow. Velocity of blood flow decreases, in the following conditions:, i. Congestive cardiac failure, ii. Hemorrhage, iii. Surgical shock, iv. Vasospasm, v. Thrombosis, vi. Embolism., , Conditions which decrease the RBC count or change, the structure, shape and size of RBC (microcytes,, macrocytes, spherocytes, sickle cells, poikilocytes, etc.), can decrease the hemoglobin content in blood., , Characteristic features of stagnant hypoxia, , iii. Formation of altered hemoglobin, , 4. Histotoxic Hypoxia, , Poisoning with chlorates, nitrates, ferricyanides,, etc. causes oxidation of iron into ferric form and the, hemoglobin is known as methemoglobin. Methemoglobin cannot combine with oxygen. Thus, the, quantity of hemoglobin available for oxygen transport is, decreased (Chapter 11)., , Stagnant hypoxia is characterized by decreased velocity, of blood flow. All other features remain normal (Table, 127.1)., , Histotoxic hypoxia is the type of hypoxia produced by, the inability of tissues to utilize oxygen., Causes for histotoxic hypoxia, Histotoxic hypoxia occurs due to cyanide or sulfide, poisoning. These poisonous substances destroy the, , TABLE 127.1: Characteristic features of different types of hypoxia, Features, 1. PO2 in arterial blood, , Hypoxic hypoxia, , Anemic hypoxia, , Stagnant hypoxia, , Histotoxic hypoxia, , Reduced, , Normal, , Normal, , Normal, , 2. Oxygen carrying capacity of blood, , Normal, , Reduced, , Normal, , Normal, , 3. Velocity of blood flow, , Normal, , Normal, , Reduced, , Normal, , 4. Utilization of oxygen by tissues, , Normal, , Normal, , Normal, , Reduced, , 100%, , 75%, , < 50%, , Not useful, , 5. Efficacy of oxygen therapy
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728 Section 9 t Respiratory System and Environmental Physiology, cellular oxidative enzymes and there is a complete, paralysis of cytochrome oxidase system. So, even if, oxygen is supplied, the tissues are not in a position to, utilize it., Characteristic features of histotoxic hypoxia, Histotoxic hypoxia is characterized by inability of, tissues to utilize oxygen even if it is delivered. All other, features remain normal (Table 127.1)., EFFECTS OF HYPOXIA, Acute and severe hypoxia leads to unconsciousness., If not treated immediately, brain death occurs. Chronic, hypoxia produces various symptoms in the body., Effects of hypoxia are of two types:, 1. Immediate effects, 2. Delayed effects., Immediate Effects, i. Effects on blood, Hypoxia induces secretion of erythropoietin from kidney., Erythropoietin increases production of RBC. This in turn,, increases the oxygen carrying capacity of blood., ii. Effects on cardiovascular system, Initially, due to the reflex stimulation of cardiac and, vasomotor centers, there is an increase in rate and, force of contraction of heart, cardiac output and blood, pressure. Later, there is reduction in the rate and force of, contraction of heart. Cardiac output and blood pressure, are also decreased., iii. Effects on respiration, Initially, respiratory rate increases due to chemoreceptor, reflex. Because of this, large amount of carbon dioxide, is washed out leading to alkalemia. Later, the respiration, tends to be shallow and periodic. Finally, the rate and, force of breathing are reduced to a great extent due to, the failure of respiratory centers., iv. Effects on digestive system, Hypoxia is associated with loss of appetite, nausea and, vomiting. Mouth becomes dry and there is a feeling of, thirst., , vi. Effects on central nervous system, In mild hypoxia, the symptoms are similar to those of, alcoholic intoxication., , Individual is depressed, apathetic with general, loss of self control. The person becomes talkative,, quarrelsome, ill-tempered and rude. The person starts, shouting, singing or crying., There is disorientation and loss of discriminative, ability and loss of power of judgment. Memory is, impaired. Weakness, lack of coordination and fatigue, of muscles are common in hypoxia., If hypoxia is acute and severe, there is a sudden, loss of consciousness. If not treated immediately, coma, occurs, which leads to death., Delayed Effects of Hypoxia, Delayed effects appear depending upon the length, and severity of the exposure to hypoxia., The person becomes highly irritable and develops, the symptoms of mountain sickness, such as nausea,, vomiting, depression, weakness and fatigue., TREATMENT FOR HYPOXIA –, OXYGEN THERAPY, Best treatment for hypoxia is oxygen therapy, i.e. treating, the affected person with oxygen. Pure oxygen or oxygen, combined with another gas is administered., Oxygen therapy is carried out by two methods:, 1. By placing the patient’s head in a ‘tent’ containing, oxygen, 2. By allowing the patient to breathe oxygen either, from a mask or an intranasal tube., Depending upon the situation, oxygen therapy can, be given either under normal atmospheric pressure or, under high pressure (hyperbaric oxygen)., In Normal Atmospheric Pressure, With normal atmospheric pressure, i.e. at one atmosphere (760 mm Hg), administration of pure oxygen is, well tolerated by the patient for long hours. However,, after 8 hours or more, lung tissues show fluid effusion, and edema. Other tissues are not affected very much, because of hemoglobin-oxygen buffer system., , v. Effects on kidneys, , In High Atmospheric Pressure –, Hyperbaric Oxygen, , Hypoxia causes increased secretion of erythropoietin, from the juxtaglomerular apparatus. And alkaline urine, is excreted., , Hyperbaric oxygen is the pure oxygen with high atmospheric pressure of 2 or more than 2 atmosphere., Hyperbaric oxygen therapy with 2 to 3 atmosphere
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Chapter 127 t Disturbances of Respiration 729, is tolerated by the patient for about 5 hours. During, this period, the dissolved form of oxygen increases in, arterial blood because the oxygen carrying capacity, of hemoglobin is limited. At this level, tissue oxygen, tension also increases to about 200 mm Hg. However,, tissues tolerate the high partial pressure of oxygen,, without much adverse effects. But, oxygen toxicity, develops when pure oxygen is administered for long, periods. Refer oxygen toxicity below., Efficacy of Oxygen Therapy in Different, Types of Hypoxia, Oxygen therapy is the best treatment for hypoxia. But it, is not effective equally in all types of hypoxia. Value of, oxygen therapy depends upon the type of hypoxia. So,, before deciding the oxygen therapy, one should recall, the physiological basis of different types of hypoxia., In hypoxic hypoxia, the oxygen therapy is 100%, useful. In anemic hypoxia, oxygen therapy is moderately, effective to about 70%. In stagnant hypoxia, the, effectiveness of oxygen therapy is less than 50%. In, histotoxic hypoxia, the oxygen therapy is not useful at, all. It is because, even if oxygen is delivered, the cells, cannot utilize oxygen., , HYPERCAPNEA, DEFINITION, Hypercapnea is the increased carbon dioxide content, of blood., CONDITIONS WHEN, HYPERCAPNEA OCCURS, Hypercapnea occurs in conditions, which leads to, blockage of respiratory pathway, as in case of asphyxia., It also occurs while breathing the air containing excess, carbon dioxide content., EFFECTS OF HYPERCAPNEA, 1. Effects on Respiration, During hypercapnea, the respiratory centers are, stimulated excessively. It leads to dyspnea., 2. Effects on Blood, The pH of blood reduces and blood becomes acidic., 3. Effects on Cardiovascular System, , OXYGEN TOXICITY (POISONING), DEFINITION AND CAUSE, Oxygen toxicity is the increased oxygen content in, tissues, beyond certain critical level. It is also called, oxygen poisoning. It occurs because of breathing pure, oxygen with a high pressure of 2 to 3 atmosphere, (hyperbaric oxygen). In this condition, an excess, amount of oxygen is transported in plasma as dissolved, form because oxygen carrying capacity of hemoglobin, is limited to 1.34 mL/g., EFFECTS OF OXYGEN TOXICITY, 1. Lung tissues are affected first with tracheobronchial irritation and pulmonary edema, 2. Metabolic rate increases in all the body tissues and, the tissues are burnt out by excess heat. Heat also, destroys cytochrome system, leading to damage of, tissues., 3. When brain is affected, first hyperirritability occurs., Later, it is followed by increased muscular twitching,, ringing in ears and dizziness., 4. Finally, the toxicity results in convulsions, coma and, death., , Hypercapnea is associated with tachycardia and, increased blood pressure. There is flushing of skin due, to peripheral vasodilatation., 4. Effects on Central Nervous System, During hypercapnea, the nervous system is also affected, resulting in headache, depression and laziness., These symptoms are followed by muscular rigidity, fine, tremors and generalized convulsions. Finally, giddiness, and loss of consciousness occur., , HYPOCAPNEA, DEFINITION, Hypocapnea is the decreased carbon dioxide content, in blood., CONDITIONS WHEN, HYPOCAPNEA OCCURS, Hypocapnea occurs in conditions associated with hypoventilation. It also occurs after prolonged hyperventilation,, because of washing out of excess carbon dioxide.
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730 Section 9 t Respiratory System and Environmental Physiology, EFFECTS OF HYPOCAPNEA, 1. Effects on Respiration, Respiratory centers are depressed, leading to decreased, rate and force of respiration., 2. Effects on Blood, The pH of blood increases, leading to respiratory alkalosis. Calcium concentration decreases. It causes, tetany, which is characterized by neuromuscular hyperexcitability and carpopedal spasm., 3. Effects on Central Nervous System, Dizziness, mental confusion, muscular twitching and, loss of consciousness are the common features of, hypocapnea., , ASPHYXIA, DEFINITION, Asphyxia is the condition characterized by combination, of hypoxia and hypercapnea, due to obstruction of air, passage., CONDITIONS WHEN ASPHYXIA OCCURS, Axphyxia develops in conditions characterized by, acute obstruction of air passage such as:, 1. Strangulation, 2. Hanging, 3. Drowning, etc., , Duration of this stage is less than 1 minute. Hypercapnea, acts on brain and produces the following effects:, i. Violent expiratory efforts, ii. Generalized convulsions, iii. Increase in heart rate, iv. Increase in arterial blood pressure, v. Loss of consciousness., 3. Stage of Collapse, Stage of collapse lasts for about 3 minutes. Severe, hypoxia produces the following effects during this, stage:, i. Depression of centers in brain and disappearance of convulsions, ii. Development of respiratory gasping occurs., During respiratory gasping, there is stretching, of the body with opening of mouth, as if gasping, for breath., iii. Dilatation of pupils, iv. Decrease in heart rate, v. Loss of all reflexes., Duration between the gasps is gradually increased, and finally death occurs., All together, asphyxia extends only for 5 minutes., The person can survive only by timely help such as, relieving the respiratory obstruction, good aeration, etc., , DYSPNEA, DEFINITION, , Effects of asphyxia develop in three stages:, 1. Stage of hyperpnea, 2. Stage of convulsions, 3. Stage of collapse., , Dyspnea means difficulty in breathing. It is otherwise, called the air hunger. Normally, the breathing goes on, without consciousness. When breathing enters the, consciousness and produces discomfort, it is called, dyspnea. Dyspnea is also defined ‘as a consciousness of necessity for increased respiratory effort’., , 1. Stage of Hyperpnea, , DYSPNEA POINT, , Hyperpnea is the first stage of asphyxia. It extends, for about 1 minute. In this stage, breathing becomes, deep and rapid. It is due to the powerful stimulation, of respiratory centers by excess of carbon dioxide., Hyperpnea is followed by dyspnea and cyanosis. Eyes, become more prominent., , Dyspnea point is the level at which there is increased, ventilation with severe breathing discomfort. The normal, person is not aware of any increase in breathing until the, pulmonary ventilation is doubled. The real discomfort, develops when ventilation increases by 4 or 5 times., , EFFECTS OF ASPHYXIA, , CONDITIONS WHEN DYSPNEA OCCURS, 2. Stage of Convulsions, Stage of convulsions is characterized mainly by convulsions (uncontrolled involuntary muscular contractions)., , Physiologically, dyspnea occurs during severe muscular exercise. The pathological conditions when, dyspnea occurs are:
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Chapter 127 t Disturbances of Respiration 731, 1. Respiratory Disorders, , CHEYNE-STOKES BREATHING, , Dyspnea occurs in the respiratory disorders, characterized by mechanical or nervous hindrance to respiratory movements and obstruction in any part of, respiratory tract. Thus, dyspnea occurs in:, i. Pneumonia, ii. Pulmonary edema, iii. Pulmonary effusion, iv. Poliomyelitis, v. Pneumothorax, vi. Severe asthma, etc., , Features of Cheyne-Stokes Breathing, , 2. Cardiac Disorders, Dyspnea is common in left ventricular failure and, decompensated mitral stenosis., , Cheyne-Stokes breathing is the periodic breathing, characterized by rhythmic hyperpnea and apnea. It is, the most common type of periodic breathing. It is marked, by two alternate patterns of respiration:, i. Hyperpneic period, ii. Apneic period., Hyperpneic period – waxing and waning of breathing, To begin with, the breathing is shallow. Force of, respiration increases gradually and reaches the, maximum (hyperpnea). Then, it decreases gradually and reaches minimum and is followed by apnea., Gradual increase followed by gradual decrease in force, of respiration is called waxing and waning of breathing, (Fig. 127.3)., , 3. Metabolic Disorders, , Apneic period, , Metabolic disorders, which cause dyspnea are, diabetic acidosis, uremia and increased hydrogen ion, concentration., , When, the force of breathing is reduced to minimum,, cessation of breathing occurs for a short period. It is, again followed by hyperpneic period and the cycle, is repeated. Duration of one cycle is about 1 minute., Sometimes, waxing and waning of breathing occurs, without apnea., , DYSPNEIC INDEX, Dyspneic index is the index between breathing reserve, and maximum breathing capacity (MBC). Breathing, reserve is the balance (difference) between MBC and, respiratory minute volume (RMV)., For example, in a normal subject, MBC is 116 L and, RMV is 6 L., , Causes for Waxing and Waning, Initially, during forced breathing, large quantity of, carbon dioxide is washed out from blood. When partial, pressure of carbon dioxide decreases, respiratory, centers become inactive. It causes apnea. During, , MBC – RMV, Dyspneic index =, , × 100, MBC, , =, , 116 – 6, , × 100, , 116, = 94.8%., Dyspnea develops when the dyspneic index, decreases below 60%., , PERIODIC BREATHING, DEFINITION AND TYPES, Periodic breathing is the abnormal or uneven respiratory, rhythm. It is of two types:, 1. Cheyne-Stokes breathing, 2. Biot breathing., , FIGURE 127.3: Periodic breathing
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732 Section 9 t Respiratory System and Environmental Physiology, apnea,, , there is accumulation of carbon dioxide, , (hypercapnea) and reduction in oxygen tension, (hypoxia). Now, the respiratory centers are activated,, , resulting in gradual increase in the force of breathing., When the force of breathing reaches maximum, the, cycle is repeated (Fig. 127.4)., Conditions when Cheyne-Stokes, Breathing Occurs, , BIOT BREATHING, Features of Biot Breathing, , Cheyne-Stokes breathing occurs in both physiological, and pathological conditions., Physiological conditions when Cheyne-Stokes, breathing occurs, i., ii., iii., iv., v., vi., , iii. During advanced renal diseases, leading to, uremia, iv. Poisoning by narcotics, v. In premature infants., , During deep sleep, In high altitude, After prolonged voluntary hyperventilation, During hibernation in animals, In newborn babies, After severe muscular exercise., , Pathological conditions when Cheyne-Stokes, breathing occurs, i. During increased intracranial pressure, ii. During advanced cardiac diseases, leading to, cardiac failure, , Biot breathing is another form of periodic breathing, characterized by period of apnea and hyperpnea., Waxing and waning of breathing do not occur (Fig., 127.2). After apneic period, hyperpnea occurs abruptly., Causes of Abrupt Apnea and Hyperpnea, Due to apnea, carbon dioxide accumulates and it, stimulates the respiratory centers, leading to hyperventilation. During hyperventilation, lot of carbon dioxide is washed out. So, the respiratory centers are not, stimulated and apnea occurs., Conditions when Biot Breathing Occurs, Biot breathing does not occur in physiological conditions. It occurs only in pathological conditions. It occurs, in conditions involving nervous disorders due to lesions, or injuries to brain., , FIGURE 127.4: Cycle of waxing and waning
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Chapter 127 t Disturbances of Respiration 733, , CYANOSIS, , SOURCES OF CARBON MONOXIDE, , DEFINITION, , Common sources for carbon monoxide are exhaust of, gasoline engines, coal mines, gases from guns, deep, wells and underground drainage system (Chapter 11)., , Cyanosis is defined as the diffused bluish coloration, of skin and mucus membrane. It is due to the presence, of large amount of reduced hemoglobin in the blood., Quantity of reduced hemoglobin should be at least 5 to, 7 g/dL in the blood to cause cyanosis., DISTRIBUTION OF CYANOSIS, When it occurs, cyanosis is distributed all over the body., But, it is more marked in certain regions where the skin, is thin. These areas are lips, cheeks, ear lobes, nose, and fingertips above the base of the nail., CONDITIONS WHEN CYANOSIS OCCURS, 1. Any condition which leads to arterial hypoxia and, stagnant hypoxia. Cyanosis does not occur in, anemic hypoxia because the hemoglobin content, itself is less. It does not occur in histotoxic hypoxia, because of tissue damage., 2. Conditions when altered hemoglobin is formed., Due to poisoning, hemoglobin is altered into, methemoglobin or sulfhemoglobin, which causes, cyanosis. The cyanotic discoloration is due to the, dark color of these compounds only and not due to, reduced hemoglobin., 3. Conditions like polycythemia when blood flow is, slow. During polycythemia, because of increased, RBC count, the viscosity of blood is increased and it, leads to sluggishness of blood flow. So the quantity, of deoxygenated blood increases, which causes, bluish discoloration of skin., , CYANOSIS AND ANEMIA, Cyanosis usually occurs only when the quantity of, reduced hemoglobin is about 5 g/dL to 7 g/dL. But,, in anemia, the hemoglobin content itself is less. So,, cyanosis cannot occur in anemia., , CARBON MONOXIDE POISONING, INTRODUCTION, Carbon monoxide is a dangerous gas since it causes, death. This gas was used by Greeks and Romans for, the execution of criminals. Carbon monoxide causes, more deaths than any other gases., , TOXIC EFFECTS OF CARBON MONOXIDE, Carbon monoxide is a dangerous gas because it, displaces oxygen from hemoglobin, by binding with same, site in hemoglobin for oxygen. So, oxygen transport and, oxygen carrying capacity of the blood are decreased., Hemoglobin has got 200 times more affinity for, carbon monoxide than for oxygen. So, even with low, partial pressure of 0.4 mm Hg of carbon monoxide in, alveoli, 50% of hemoglobin is saturated with it. It can be, dangerous if the partial pressure increases to 0.6 mm, Hg, (1/1,000 of volume concentration in air). Presence, of carboxyhemoglobin decreases the release of, oxygen from hemoglobin and the oxygen-hemoglobin, dissociation curve shifts to left., It is still more dangerous because, during carbon, monoxide poisoning, the partial pressure of oxygen, in blood may normal in spite of low oxygen content of, blood. So, the regular feedback stimulation of respiratory, centers by hypoxia does not take place because of, normal partial pressure of oxygen., However, low oxygen content in blood affects the, brain, resulting in unconsciousness. The condition becomes fatal if immediate treatment is not given., Carbon monoxide is toxic to the cytochrome system, in cells also., SYMPTOMS OF CARBON, MONOXIDE POISONING, Symptoms of carbon monoxide poisoning depend upon, its concentration:, 1. While breathing air with 1% of carbon monoxide,, saturation of hemoglobin with carbon monoxide, becomes 15% to 20%. Mild symptoms like, headache and nausea appear., 2. While breathing air containing carbon monoxide, more than 1%, the saturation becomes 30% to 40%., It causes convulsions, cardiorespiratory arrest,, loss of consciousness and coma., 3. When hemoglobin saturation is above 50%, death, occurs.
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734 Section 9 t Respiratory System and Environmental Physiology, TREATMENT FOR CARBON, MONOXIDE POISONING, Treatment for carbon monoxide poisoning includes:, 1. Immediate termination of exposure to carbon, monoxide, 2. Providing adequate ventilation and artificial, respiration, 3. Administration of 100% oxygen if possible. It is to, replace carbon monoxide, 4. Administration of air with few percent of carbon, dioxide, if possible. It is done to stimulate the, respiratory centers., , TYPES AND EFFECTS, Pneumothorax is of three types:, 1. Open pneumothorax, 2. Closed pneumothorax, 3. Tension pneumothorax., 1. Open Pneumothorax, After the injury, an open communication is developed, between pleural cavity and exterior. It is known as open, pneumothorax. Air enters the pleural cavity during, inspiration and comes out during expiration. Collapse of, lungs causes hypoxia, hypercapnea, dyspnea, cyanosis, and asphyxia., , ATELECTASIS, 2. Closed Pneumothorax, DEFINITION, Atelectasis refers to partial or complete collapse of, lungs. When a large portion of lung is collapsed, the, partial pressure of oxygen is reduced in blood, leading, to respiratory disturbances., CAUSES, 1. Deficiency or inactivation of surfactant. It causes, collapse of lungs due to increased surface tension,, which leads to respiratory distress syndrome., 2. Obstruction of a bronchus or a bronchiole. In this, condition, the alveoli attached to the bronchus or, bronchiole are collapsed., 3. Presence of air (pneumothorax), fluid (hydrothorax),, blood (hemothorax) or pus (pyothorax) in the pleural, space., , During a mild injury, air enters into the pleural cavity and, then the hole in the pleura is sealed and closed. It is, called the closed pneumothorax. It does not produce, hypoxia. Air from the pleural cavity is absorbed slowly., 3. Tension Pneumothorax, During injuries, sometimes the tissues over the hole, in the chest wall or the lungs behave like a fluttering, valve. It permits entrance of air into pleural cavity, during inspiration but prevents the exit of air during, expiration, due to its valvular nature. Because of this,, the intrapleural pressure increases above atmospheric, pressure. This condition is very fatal, since it results in, collapse of the whole lung., , PNEUMONIA, , EFFECTS, , DEFINITION, , Effects of atelectasis are decreased partial pressure of, oxygen, leading to dyspnea., , Pneumonia is the inflammation of lung tissues, followed, by the accumulation of blood cells, fibrin and exudates, in the alveoli. Affected part of the lungs becomes, , PNEUMOTHORAX, , consolidated., , DEFINITION, , CAUSES, , Pneumothorax is the presence of air in pleural space., Intrapleural pressure, which is always negative,, becomes positive in pneumothorax and it causes, collapse of lungs., , Inflammation of lung is caused by:, 1. Bacterial or viral infection, 2. Inhaling noxious chemical substance., , CAUSES, , Pneumonia is of two types, namely lobar pneumonia, and lobular pneumonia. When it is lobular and, associated with inflammation of bronchi, it is known as, , Air enters the pleural cavity because of damage of, chest wall or lungs during accidents, bullet injury or, stab injury., , TYPES, , bronchopneumonia.
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Chapter 127 t Disturbances of Respiration 735, EFFECTS, , FEATURES, , Following are the effects of pneumonia:, 1. Fever, 2. Compression of chest and chest pain, 3. Shallow breathing, 4. Cyanosis, 5. Sleeplessness (insomnia), 6. Delirium., , Asthma is a paroxysmal (sudden) disorder because, the attack commences and ends abruptly. During the, attack, the difficulty is felt both during inspiration and, expiration. Bronchioles have inherent tendency to dilate, during inspiration and constrict during expiration. So,, more difficulty is experienced during expiration. During, expiration, great effort is exerted by all the expiratory, muscles causing compression of chest. There is severe, contraction of abdominal muscles also. So, air from, lungs is pushed through the constricted bronchioles,, producing a whistling sound., Because of difficulty during expiration, the lungs are, not deflated completely, so that the residual volume and, functional residual capacity are increased., There is reduction in:, i. Tidal volume, ii. Vital capacity, iii. Forced expiratory volume in 1 second (FEV1), iv. Alveolar ventilation, v. Partial pressure of oxygen in blood., Carbon dioxide accumulates, resulting in acidosis,, dyspnea and cyanosis., , Delirium, Delirium is the extreme mental condition that is caused, by cerebral hypoxia., Features of delirium, i. Confused mental state (confused way of thought, and speech), ii. Illusion (misinterpretation of a sensory stimulus), iii. Hallucination (feeling of sensations such as touch,, pain, taste, smell, etc. without any stimulus), iv. Disorientation (loss of ability to recognize place,, time and other persons), v. Hyperexcitability, vi. Loss of memory., , PULMONARY EDEMA, , BRONCHIAL ASTHMA, , DEFINITION, , DEFINITION, , Pulmonary edema is the accumulation of serous fluid in, the alveoli and the interstitial tissue of lungs., , Bronchial asthma is the respiratory disease characterized, by difficult breathing with wheezing. Wheezing refers, to whistling type of respiration. It is due to bronchiolar, constriction, caused by spastic contraction of smooth, muscles in bronchioles, leading to obstruction of air, passage. Obstruction is further exaggerated by the, edema of mucus membrane and accumulation of, mucus in the lumen of bronchioles., CAUSES, 1. Inflammation of air passage: Leukotrienes released, from eosinophils and mast cells during inflammation, cause bronchospasm., 2. Hypersensitivity of afferent glossopharyngeal, and vagal ending in larynx and afferent trigeminal, endings in nose: Hypersensitivity of these nerve, endings is produced by some allergic substances, like foreign proteins., 3. Pulmonary edema and congestion of lungs caused, by left ventricular failure: Asthma developed due to, this condition is called cardiac asthma., , CAUSES, 1. Increased pulmonary capillary pressure due to left, ventricular failure or mitral valve disease, 2. Pneumonia, 3. Breathing harmful chemicals like chlorine or sulfur, dioxide., EFFECTS, Effects of pulmonary edema are severe dyspnea, cough, with frothy bloodstained expectoration, cyanosis and, cold extremities., Chronic interstitial edema leads to asthma. Alveolar edema is fatal and causes sudden death due to, suffocation., , PLEURAL EFFUSION, DEFINITION, Pleural effusion is the accumulation of large amount of, fluid in the pleural cavity.
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736 Section 9 t Respiratory System and Environmental Physiology, CAUSES, 1. Blockage of lymphatic drainage, 2. Excessive transudation of fluid from pulmonary, capillaries due to increased pulmonary capillary, pressure caused by left ventricular failure, 3. Inflammation of pleural membrane which damages, the capillary membrane, allowing leakage of fluid, and plasma proteins into the pleural cavity., FEATURES, Pleural effusion causes atelectasis, leading to dyspnea, and other respiratory disturbances., , PULMONARY TUBERCULOSIS, DEFINITION, Tuberculosis is the disease caused by tubercle bacilli., This disease can affect any organ in the body. However,, the lungs are affected more commonly. Infected tissue is, invaded by macrophages and later it becomes fibrous., Affected tissue is called tubercle., FEATURES, Initially, alveoli in the affected part become nonfunctioning, due to thickness of respiratory membrane., If a large part of lungs is involved, the diffusing capacity, is very much reduced. In severe conditions, the, destruction of the lung tissue is followed by formation of, large abscess cavities., , EMPHYSEMA, DEFINITION AND CAUSES, Emphysema is one of the obstructive respiratory, diseases in which lung tissues are extensively damaged., Damage of lung tissues results in loss of alveolar walls., Because of this, the elastic recoil of lungs is also lost., Emphysema is caused by:, 1. Cigarette smoking, 2. Exposure to oxidant gases, 3. Untreated bronchitis., DEVELOPMENT OF EMPHYSEMA, 1. Smoke or oxidant gases irritate the bronchi and, bronchioles, leading to chronic infection, , 2. It increases the mucus secretion from the respiratory, epithelial cells causing obstruction of air passage, 3. Cilia of respiratory epithelial cells are partially, paralyzed and the movement is very much reduced., Because of this, the mucus cannot be removed from, the respiratory passage., 4. Destruction of alveolar mucus membrane, 5. Destruction of elastic tissues occur. Normally,, there is loss of some elastic tissues because of, the proteolytic enzyme called elastase. But, that, is very much negligible. Moreover, liver produces, elastase inhibitors especially, α1-antitrypsin,, which prevents the destruction of elastic tissues., But, due to heavy smoking or because of constant, exposure to oxidant gases, the pulmonary alveolar, macrophages increase in number. Macrophages, release a chemical substance, which attracts a, large number of leukocytes. Leukocytes release, proteases including elastase, which destroy the, elastic tissues of the lungs., EFFECTS OF EMPHYSEMA, 1. Airway resistance increases several times due to, the bronchiolar obstruction. So, the movement of, air through the respiratory passage becomes very, difficult. It is more pronounced during expiration., 2. Due to the destruction of alveolar membrane and, elastic tissues, the lungs become loose and floppy., So, the diffusing capacity reduces to a great extent., However, lung compliance increases (Chapter, 120) and the aeration of blood is impaired. Enough, oxygen cannot diffuse into blood and carbon, dioxide cannot diffuse out., 3. Obstruction also affects ventilation-perfusion ratio,, resulting in poor aeration of blood, 4. Due to the destruction of lung tissues, the number, of pulmonary capillaries also decreases. It increases the pulmonary vascular resistance, leading to pulmonary hypertension., 5. Over the years, chronic emphysema could lead, to hypoxia and hypercapnea. It will finally cause, prolonged and severe air hunger (dyspnea), leading, to death.
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Chapter, , High Altitude and, Space Physiology, , 128, , HIGH ALTITUDE, BAROMETRIC PRESSURE AND PARTIAL PRESSURE OF, OXYGEN AT DIFFERENT ALTITUDES, CHANGES IN THE BODY AT HIGH ALTITUDE, , , , , , EFFECTS OF HYPOXIA, EFFECTS OF EXPANSION OF GASES ON THE BODY, EFFECTS OF REDUCED ATMOSPHERIC TEMPERATURE, EFFECTS OF LIGHT RAYS, , MOUNTAIN SICKNESS, , , , , DEFINITION, SYMPTOMS, TREATMENT, , ACCLIMATIZATION, , , , DEFINITION, CHANGES DURING ACCLIMATIZATION, , AVIATION PHYSIOLOGY, , , , , , ACCELERATIVE FORCE, GRAVITATIONAL FORCE, EFFECTS OF GRAVITATIONAL FORCES ON THE BODY, PREVENTION OF EFFECTS OF G FORCES ON THE BODY, , SPACE PHYSIOLOGY, , , EFFECTS OF TRAVEL BY SPACECRAFT, , HIGH ALTITUDE, High altitude is the region of earth located at an altitude, of above 8,000 feet from mean sea level. People can, ascend up to this level, without any adverse effect., Different altitudes are given in Table 128.1., Characteristic feature of high altitude is the low, barometric pressure. However, amount of oxygen, available in the atmosphere is same as that of sea level., Due to low barometric pressure, partial pressure of, gases, particularly oxygen proportionally decreases. It, leads to hypoxia., Carbon dioxide in high altitude is very much, negligible and it does not create any problem., , TABLE 128.1: Different altitudes, Altitude, High altitude, Very high altitude, Extreme altitude, , Feet, , Meter, , 8,000 to 13,000, , 2,500 to 4,000, , 13,000 to 18,000, , 4,000 to 5,500, , > 18,000, , > 5,500, , BAROMETRIC PRESSURE AND, PARTIAL PRESSURE OF OXYGEN, AT DIFFERENT ALTITUDES, Barometric pressure decreases at different altitudes., Accordingly, partial pressure of oxygen also decreases
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738 Section 9 t Respiratory System and Environmental Physiology, and produces various effects on the body. Barometric, pressure and partial pressure of oxygen at different, altitudes and their common effects on the body are, given in Table 128.2., , CHANGES IN THE BODY AT, HIGH ALTITUDE, When a person is exposed to high altitude, particularly, by rapid ascent, the various systems in the body, cannot cope with lowered oxygen tension and effects, of hypoxia start. Besides hypoxia, some other factors, are also responsible for the changes in functions of the, body at high altitude., Factors Affecting Physiological Functions, at High Altitude, 1., 2., 3., 4., , Hypoxia, Expansion of gases, Fall in atmospheric temperature, Light rays., , EFFECTS OF HYPOXIA, Refer Chapter 127 for effects of hypoxia., , EFFECTS OF EXPANSION OF GASES, ON THE BODY, Volume of gases increases when the barometric, pressure is reduced. So at high altitude, due to the, decreased barometric pressure, volume of all gases, increases in atmospheric air, as well as in the body., At the sea level with atmospheric pressure of 760, mm Hg, if the volume of gas is 1 liter, at the height of, 18,000 feet (where atmospheric pressure is 379 mm, Hg), it becomes 2 liter. And it becomes 3 liter, at the, height of 30,000 feet (where atmospheric pressure is, 226 mm Hg)., Expansion of gases in GI tract causes painful, distention of stomach and intestine. It is minimized by, supporting the abdomen with a belt or by evacuation, of the gases. Expansion of gases also destroys the, alveoli., During very rapid ascent from sea level to over 30,000, feet height, the gases evolve as bubbles, particularly, nitrogen, resulting in decompression sickness. Refer, Chapter 129 for details of decompression sickness., , TABLE 128.2: Barometric pressure, partial pressure of oxygen and common effects at different altitudes, Altitude, (feet), , Barometric, pressure, (mm Hg), , Partial pressure, of oxygen, (mm Hg), , Sea level, , 760, , 159, , –, , 5,000, , 600, , 132, , No hypoxia, , 10,000, , 523, , 110, , Mild symptoms of hypoxia start appearing, , 90, , Moderate hypoxia develops with following symptoms:, – Reduction in visual acuity, – Effects on mental functions:, – Improper judgment and, – Feeling of over confidence, , 15,000, , 400, , Common effects, , 20,000, , 349, , 73, , Severe hypoxia appears with cardiorespiratory symptoms such as, – Increase in heart rate and cardiac output, – Increase in respiratory rate and respiratory minute volume, This is the highest level for permanent inhabitants, , 25,000, , 250, , 62, , This is the critical altitude for survival, – Hypoxia becomes severe, – Breathing oxygen becomes essential, , 29,628, , 235, , 49, , This is the height of Mount Everest, , 30,000, , 226, , 47, , Symptoms become severe even with oxygen, , 50,000, , 87, , 18, , Hypoxia becomes more severe even with pure oxygen
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Chapter 128 t High Altitude and Space Physiology 739, EFFECTS OF REDUCED, ATMOSPHERIC TEMPERATURE, Environmental temperature falls gradually at high, altitudes. The temperature decreases to about 0°C, at the height of 10,000 feet. It becomes –22°C at the, height of 20,000 feet. At the altitude of 40,000 feet, the, temperature falls to –44°C. Injury due to cold or frostbite, occurs if the body is not adequately protected by warm, clothing., , 4. Nervous System, Symptoms occuring in nervous system are headache,, depression, disorientation, irritability, lack of sleep,, weakness and fatigue. These symptoms are developed, because of cerebral edema. Sudden exposure to, hypoxia in high altitude causes vasodilatation in brain., Autoregulation mechanism of cerebral blood flow fails, to cope with hypoxia. It leads to an increased capillary, pressure and leakage of fluid from capillaries into the, brain tissues., , EFFECTS OF LIGHT RAYS, Skin becomes susceptible for injury due to many, harmful rays like ultraviolet rays of sunlight. Moreover,, the sunrays reflected by the snow might injure the, retina of the eye, if it is not protected with suitable tinted, glasses., Severity of all these effects depends upon the, speed at which one ascends in high altitude. The, effects are comparatively milder or moderate in slow, ascent and are severe in rapid ascent., , MOUNTAIN SICKNESS, DEFINITION, Mountain sickness is the condition characterized, by adverse effects of hypoxia at high altitude. It is, commonly developed in persons going to high altitude, for the first time. It occurs within a day in these persons,, before they get acclimatized to the altitude., SYMPTOMS, In mountain sickness, the symptoms occur mostly in, digestive system, cardiovascular system, respiratory, system and nervous system. Symptoms of mountain, sickness are:, 1. Digestive System, Loss of appetite, nausea and vomiting occur because of, expansion of gases in GI tract., 2. Cardiovascular System, Heart rate and force of contraction of heart increases., , TREATMENT, Symptoms of mountain sickness disappear by breathing, oxygen., , ACCLIMATIZATION, DEFINITION, Acclimatization refers to the adaptations or the, adjustments by the body in high altitude. While staying, at high altitudes for several days to several weeks, a, person slowly gets adapted or adjusted to the low, oxygen tension, so that hypoxic effects are reduced. It, enables the person to ascent further., CHANGES DURING ACCLIMATIZATION, Various changes that take place during acclimatization, help the body to cope with adverse effects of hypoxia, at high altitude. Following changes occur in the body, during acclimatization:, 1. Changes in Blood, During acclimatization, RBC count increases and, packed cell volume rises from normal value of 45% to, about 59%. Hemoglobin content in the blood rises from, 15 g% to 20 g%. So, the oxygen carrying capacity of the, blood is increased. Thus, more oxygen can be carried, to tissues, in spite of hypoxia. Increase in packed cell, volume and hemoglobin content is due to erythropoietin, actions., Increase in RBC count, packed cell volume and, hemoglobin content is due to erythropoietin, that is, released from juxtaglomerular apparatus of kidney., , 3. Respiratory System, Pulmonary blood pressure increases due to increased, blood flow. Blood flow increases because of vasodi, latation induced by hypoxia. Increased pulmonary blood, pressure results in pulmonary edema, which casus, breathlessness., , 2. Changes in Cardiovascular System, Overall activity of cardiovascular system is increased in, high altitude. There is an increase in rate and force of, contraction of the heart and cardiac output. Vascularity, in the body is increased due to vasodilatation induced
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740 Section 9 t Respiratory System and Environmental Physiology, by hypoxia. So, blood flow to vital organs such as heart,, brain, muscles, etc. increases., , produce severe physiological effects. Accelerative, forces are developed in the flight during linear, radial or, centripetal and angular acceleration., , 3. Changes in Respiratory System, i. Pulmonary ventilation, Pulmonary ventilation increases up to 65%. This is the, immediate compensation for hypoxia in high altitude, and this alone helps the person to ascend several, thousand feet. Increase in pulmonary ventilation is due, to the stimulation of chemoreceptors (Chapter 126)., ii. Pulmonary hypertension, Increased cardiac output increases the pulmonary blood, flow that leads to pulmonary hypertension. It is very, common even in persons acclimatized to high altitude., In some of these persons, pulmonary hypertension is, associated with right ventricular hypertrophy., iii. Diffusing capacity of gases, Due to increased pulmonary blood flow and increased, ventilation, diffusing capacity of gases increases in, alveoli. It enables more diffusion of oxygen in blood., 4. Changes in Tissues, Both in human beings and animals residing at high, altitudes permanently, the cellular oxidative enzymes, involved in metabolic reactions are more than the inhabi, tants at sea level., Even when a sea level inhabitant stays at high, altitude for certain period, the amount of oxidative, enzymes is not increased. So, the elevation in the, amount of oxidative enzymes occurs only in fully, acclimatized persons. An increase in the number of, mitochondria is observed in these persons., , AVIATION PHYSIOLOGY, Aviation physiology is the study of physiological, responses of the body in aviation environment., Flying exerts great effects on the body through, accelerative forces and gravitational forces, which are, developed during the flight maneuvering. Pilots and, other crew members of aircraft are trained to overcome, the effects of these forces., ACCELERATIVE FORCE, Acceleration means change in velocity. Flying straight, in horizontal plane with constant velocity has minimum, effects on the body. However, changes in velocity, , GRAVITATIONAL FORCE, Gravitational force (G force) is the major factor that, develops accelerative force. G force and the direction, in which body receives the force are responsible for, physiological changes in the body during acceleration., Force or pull of gravity upon the body is expressed, in G unit. On the earth, this pull is responsible for body, weight. Force of gravity while sitting, standing or lying, position is considered to be equal to body weight and it, is referred as 1 G. G unit increases in acceleration. If we, say that G unit increases to 5 G during acceleration, it, means that the force of gravity on body at that moment, is equal to five times the body weight., While traveling in an airplane, elevator or a car,, if there is a sudden change in speed or direction,, passengers are thrown or centrifuged in the opposite, direction. It is because of change in the G unit. G unit may, increase or decrease. Increase in G unit is called positive, G and decrease in G unit is called negative G. Positive, G occurs while increasing the speed (acceleration)., Negative G occurs while decreasing the speed (slowing, down; deceleration). G unit is altered during the change, in direction also., While flying, both positive G and negative G cause, physiological changes in the body., EFFECTS OF GRAVITATIONAL FORCES, ON THE BODY, Effects of Positive G, Major effects of positive G during acceleration are, on the blood circulation. When G unit increases to, about 4 to 5 G, blood is pushed toward the lower, parts of the body including abdomen. So the cardiac, output decreases, resulting in reduced blood supply, to the brain and eyes. Decreased blood flow in turn,, decreases oxygen supply (hypoxia) to the head and, leads to following disturbances:, 1. Grayout, Grayout is the graying of vision that occurs when, blood flow to eyes starts diminishing. It occurs because, the retina is more sensitive to hypoxia than brain., Though physical impairment does not occur, grayout, is considered as a warning for decreased blood flow, to head.
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Chapter 128 t High Altitude and Space Physiology 741, 2. Blackout, Blackout is the complete loss of vision that occurs, when retinal function is affected by hypoxia. Conscious, ness and muscular activities are still retained. But it, indicates the risk of loss of consciousness., , and neck. It causes bradycardia or irregular heartbeat,, which adds to stagnation of blood in head. All these, factors ultimately lead to unconsciousness., PREVENTION OF EFFECTS OF G FORCES, ON THE BODY, , 3. Loss of consciousness, When force increases beyond 5 G, hypoxia reaches, the critical level and causes loss of consciousness., It may be associated with convulsions. Unconscious, state may last for about 15 seconds. After recovery, from unconsciousness, the person needs another 10, to 15 minutes for orientation. If the affected person, happens to be a lone pilot, then he will loose control, over his aircraft., , Body can be protected from the effects of G forces,, particularly positive G by the following methods:, 1. By Using Abdominal Belts, Pooling of blood in the abdominal blood vessels is, prevented by using abdominal belt and leaning forward, while sitting in the aircraft. This procedure postpones, grayout or blackout., , 4. Fracture of bones, When force increases to about 20 G, bones, particularly, the spine, becomes susceptible for fracture even during, sitting posture., , 2. By Using Anti-G Suit, AntiG suit exerts a positive pressure on lower limbs, and abdomen and prevents the pooling of blood in lower, part of the body., , Effects of Negative G, Negative G develops while flying downwards (inverted, flying). It causes the following disturbances:, 1. Hyperemia, When the force decreases to –4 to –6 G, hyperemia, (abnormal increase in blood flow) occurs in head, because the blood is pushed towards head. Sometimes, the blood accumulates in head, resulting in brain, edema. There is congestion, flushing of face and mild, headache. Negative G at this level is tolerable and the, effects are only momentary. Brain also can withstand, hyperemia in such conditions., 2. Redout and headache, Redout is the blurring of vision and sudden reddening, of visual field, caused by engorgement of blood vessels, in head. When the negative G reaches to about –15 G, to –20 G, there is dilatation and congestion of blood, vessels in head and eyes, resulting in redout and, headache. Blood vessels in brain may not be affected, much because of CSF. When blood accumulates in, brain, there is simultaneous pooling of CSF in cranium., The high pressure exerted by CSF acts as a cushion, (buffer) and protects the blood vessels of brain., 3. Loss of consciousness, High negative G affects the body by other means. It, increases the pressure in the blood vessels of chest, , SPACE PHYSIOLOGY, Space physiology is the study of physiological responses, of the body in space and spacecrafts., Major differences between the environments of earth, and space are atmosphere, radiation and gravity. These, three factors challenge the human survival in space., Atmospheric factors include atmospheric pressure,, temperature, humidity and gas composition., Spacecraft or spacelab is provided with stable, and sophisticated environmental control system, which, maintains all the atmospheric factors close to earth’s, environment. Astronauts also wear launch and entry, suit (LES). LES is a pressurized suit that protects the, body from space environment., Another factor which affects the body in the space, is weightlessness. Weightlessness is because of, absence of gravity (microgravity)., EFFECTS OF TRAVEL BY SPACECRAFT, While traveling by spacecraft, the astronauts experi, ence some intense symptoms only during blast off,, due to acceleration and during landing because of, deceleration. Otherwise, the accelerative forces, are least while traveling in a spacecraft, since the, spacecraft cannot make rapid changes in speed or, direction like an aircraft.
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742 Section 9 t Respiratory System and Environmental Physiology, Most of the physiological changes occur due to, weightlessness in space travel. These changes are, responsible for the adaptation of astronaut’s body to, space environment. Further, problems develop only, when they return to earth. They require a longtime to, readapt to earth environment., Effects of weightlessness in spacecraft are:, 1. Effects on Cardiovascular, Systems and Kidneys, Cardiovascular changes are due to the fluid shift. Due, to absence of gravity, blood moves from lower part to, upper part of the body (upper trunk and head). It causes, enlargement of heart to cope up with increased blood, flow. In addition, there is an accumulation of other body, fluids in upper part. Now, the compensatory mechanism, in the body interprets the increase in blood and other, fluids as a serious threat and starts correcting it by, excreting large amount of fluid through kidneys. It, causes decrease in blood volume and the heart need, not pump the blood against gravity in space. So, initially, enlarged heart starts shrinking slowly and becomes, small. Thus during the initial fluid shift, astronauts, experience dizziness or feeling of fainting., Along with water, kidneys excrete electrolytes also., Because of this, osmolarity of body fluids is not altered., So the thirst center is not stimulated and the astronauts, do not feel thirsty during space travel., , 2. Effects on Blood, Plasma volume decreases due to excretion of fluid, through urine. RBC count also decreases and it is called, space anemia., 3. Effects on Musculoskeletal System, Because of microgravity in space, the muscles need not, support the body against gravity. Astronauts move by, floating instead of using their legs. This leads to decrease, in muscle mass and muscle strength. Endurance of, the muscles also decreases. Bones become weak., Osteoclastic activity increases during space travel., Calcium removed from bone is excreted through urine., 4. Effects on Immune System, Space travel causes suppression of immune system in, the body., 5. Space Motion Sickness, After obtaining weightlessness, some astronauts, develop space motion sickness. It is characterized by, nausea, vomiting, headache and malaise (generalized, feeling of discomfort or lack of wellbeing or illness that, is associated with sensation of exhaustion). It persists, for two or three days and then disappears. It is thought, that the motion sickness occurs due to abnormal, stimulation of vestibular apparatus and fluid shift.
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Deep Sea Physiology, , Chapter, , 129, , INRODUCTION, BAROMETRIC PRESSURE AT DIFFERENT DEPTHS, EFFECT OF HIGH BAROMETRIC PRESSURE – NITROGEN NARCOSIS, , , , , , MECHANISM, SYMPTOMS, PREVENTION, TREATMENT, , DECOMPRESSION SICKNESS, , , , , , , DEFINITION, CAUSE, SYMPTOMS, PREVENTION, TREATMENT, , SCUBA, , INTRODUCTION, In high altitude, the problem is with low atmospheric, (barometric) pressure. In deep sea or mines, the, problem is with high barometric pressure. Increased, pressure creates two major problems:, 1. Compression effect on the body and internal, organs, 2. Decrease in volume of gases., , BAROMETRIC PRESSURE, AT DIFFERENT DEPTHS, At sea level, the barometric pressure is 760 mm Hg,, which is referred as 1 atmosphere. At the depth of, every 33 feet (about 10 m), the pressure increases by 1, atmosphere. Thus, at the depth of 33 feet, the pressure, is 2 atmospheres. It is due to the air above water and, the weight of water itself. Pressure at different depths is, given in Table 129.1., , EFFECT OF HIGH BAROMETRIC, PRESSURE – NITROGEN NARCOSIS, Narcosis refers to unconsciousness or stupor produced, by drugs. Stupor refers to lethargy with suppression, of sensations and feelings. Nitrogen narcosis means, narcotic effect produced by nitrogen at high pressure., Nitrogen narcosis is common in deep sea divers,, who breathe compressed air (air under high pressure)., Breathing compressed air is essential for a deep sea, diver or an underwater tunnel worker. It is to equalize, the surrounding high pressure acting on thoracic wall, and abdomen., Eighty percent of the atmospheric air is nitrogen., Being an inert gas, it does not produce any known effect, on the functions of the body at normal atmospheric, pressure (sea level). When a person breathes, pressurized air as in deep sea, the narcotic effect of, nitrogen appears. It produces an altered mental state,, similar to alcoholic intoxication.
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744 Section 9 t Respiratory System and Environmental Physiology, TABLE 129.1: Barometric pressure and its effects at different depth, Depth, (feet), Sea level, 33, , Atmospheric pressure, (mm Hg), , Effects on the subject, , 1, , –, , 2, , –, , 66, , 3, , –, , 100, , 4, , Symptoms of nitrogen narcosis appear, , 133, , 5, , Lack of concentration, Becomes jovial and careless, , 166, , 6, , Starts feeling drowsy, , 200, , 7, , Feels fatigued, weak and careless, , 233, , 8, , Looses power of judgment, Unable to do skilled work, , 266, , 9, , Becomes unconscious, , Barometric pressure: 1 atmosphere = 760 mm Hg, , MECHANISM, Nitrogen is soluble in fat. During compression by high, barometric pressure in deep sea, nitrogen escapes, from blood vessels and gets dissolved in the fat, present in various parts of the body, especially the, neuronal membranes. Dissolved nitrogen acts like an, anesthetic agent suppressing the neuronal excitability., Nitrogen remains in dissolved form in the fat till the, person remains in the deep sea., SYMPTOMS, 1. First symptom starts appearing at a depth of 120, feet. The person becomes very jovial, careless, and does not understand the seriousness of the, conditions., 2. At the depth of 150 to 200 feet, the person becomes, drowsy, 3. At 200 to 250 feet depth, the person becomes, extremely fatigued and weak. There is loss of con, centration and judgment. Ability to perform skilled, work or movements is also lost., 4. Beyond the depth of 250 feet, the person becomes, unconscious., , Nitrogen narcosis may be prevented by limiting, the depth of dives. Effects of nitrogen narcosis may, also be minimized by safe diving procedures such, as proper maintenance of equipments and less work, effort. In addition, alcohol consumption should be, avoided 24 hours before diving., TREATMENT, Symptoms of nitrogen narcosis completely disappear, when the diver returns to a depth of 60 feet. There, is no need for any further treatment since nitrogen, narcosis does not have any hangover effect. However,, the physician should be consulted if the diver loses, consciousness., , DECOMPRESSION SICKNESS, DEFINITION, Decompression sickness is the disorder that occurs, when a person returns rapidly to normal surroundings, (atmospheric pressure) from the area of high, atmospheric pressure like deep sea. It is also known, as dysbarism, compressed air sickness, caisson, disease, bends or diver’s palsy., , PREVENTION, Nitrogen narcosis can be prevented by mixing helium, with oxygen. Helium is used as a substitute for nitrogen,, to dilute oxygen during deep water diving. Helium also, produces some effects like nausea and dizziness. But,, the adverse effects of helium are less severe than, nitrogen narcosis., , CAUSE, High barometric pressure at deep sea leads to, compression of gases in the body. Compression reduces, the volume of gases., Among the respiratory gases, oxygen is utilized, by tissues. Carbon dioxide can be expired out. But,
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Chapter 129 t Deep Sea Physiology 745, nitrogen, which is present in high concentration, i.e., 80% is an inert gas. So, it is neither utilized nor expired., When nitrogen is compressed by high atmospheric, pressure in deep sea, it escapes from blood vessels, and enters the organs. As it is fat soluble, it gets, dissolved in the fat of the tissues and tissue fluids. It is, very common in the brain tissues., As long as the person remains in deep sea, nitro, gen remains in solution and does not cause any pro, blem. But, if the person ascends rapidly and returns to, atmospheric pressure, decompression sickness occurs., Due to sudden return to atmospheric pressure, the, nitrogen is decompressed and escapes from the tissues, at a faster rate. Being a gas, it forms bubbles while, escaping rapidly. The bubbles travel through blood, vessels and ducts. In many places, the bubbles obstruct, the blood flow and produce air embolism, leading to, decompression sickness., Underground tunnel workers who use the caissons, (pressurized chambers) also develop decompression, (caisson disease) sickness. Pressure in the chamber, is increased to prevent the entry of water inside., Decompression sickness also occurs in a person, who ascends up rapidly from sea level in an airplane, without any precaution., SYMPTOMS, Symptoms of decompression sickness are mainly due, to the escape of nitrogen from tissues in the form of, bubbles., Symptoms are:, 1. Severe pain in tissues, particularly the joints, pro, duced by nitrogen bubbles in the myelin sheath of, sensory nerve fibers, 2. Sensation of numbness, tingling or pricking (par, esthesia) and itching, 3. Temporary paralysis due to nitrogen bubbles in the, myelin sheath of motor nerve fibers, 4. Muscle cramps associated with severe pain, 5. Occlusion of coronary arteries followed by coronary, ischemia, caused by bubbles in the blood, , 6. Occlusion of blood vessels in brain and spinal cord, also, 7. Damage of tissues of brain and spinal cord because, of obstruction of blood vessels by the bubbles, 8. Dizziness, paralysis of muscle, shortness of breath, and choking occur, 9. Finally, fatigue, unconsciousness and death., PREVENTION, Decompression sickness is prevented by proper, precautionary measures. While returning to mean sea, level, the ascent should be very slow with short stay, at regular intervals. Stepwise ascent allows nitrogen, to come back to the blood, without forming bubbles. It, prevents the decompression sickness., TREATMENT, If a person is affected by decompression sickness, first, recompression should be done. It is done by keeping, the person in a recompression chamber. Then, he is, brought back to atmospheric pressure by reducing the, pressure slowly., Hyperbaric oxygen therapy may be useful., , SCUBA, SCUBA (selfcontained underwater breathing appara, tus) is used by the deep sea divers and the underwater, tunnel workers, to prevent the ill effects of increased, barometric pressure in deep sea or tunnels., This instrument can be easily carried and it, contains air cylinders, valve system and a mask. By, using this instrument, it is possible to breathe air or, gas mixture without high pressure. Also, because of, the valve system, only the amount of air necessary, during inspiration enters the mask and the expired air, is expelled out of the mask., Disadvantage of this instrument is that the person, using this can remain in the sea or tunnel only for a, short period. Especially, beyond the depth of 150 feet,, the person can stay only for few minutes.
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Effects of Exposure, to Cold and Heat, , Chapter, , 130, , EFFECTS OF EXPOSURE TO COLD, , , , HEAT PRODUCTION, PREVENTION OF HEAT LOSS, , EFFECTS OF EXPOSURE TO SEVERE COLD, , , , LOSS OF TEMPERATURE REGULATING CAPACITY, FROSTBITE, , EFFECTS OF EXPOSURE TO HEAT, , , , , , HEAT EXHAUSTION, DEHYDRATION EXHAUSTION, HEAT CRAMPS, HEATSTROKE – SUNSTROKE, , EFFECTS OF EXPOSURE TO COLD, During exposure to cold, the body temperature is, maintained by two mechanisms (Chapter 63)., 1. Heat production, 2. Prevention of heat loss., HEAT PRODUCTION, When body is exposed to cold, heat is produced by the, following activities:, 1. By Accelerating Metabolic Activities, Heat gain center in hypothalamus is stimulated during, exposure to cold. It activates the sympathetic centers,, which cause secretion of adrenaline and noradrenaline., These hormones, especially adrenaline increase heat, production by accelerating cellular metabolic activities., 2. By Shivering, Shivering is the increased involuntary muscular activity, with slight vibration of the body in response to fear,, onset of fever or exposure to cold. Shivering occurs, when the body temperature falls to about 25°C (77°F)., Primary motor center for shivering is situated in posterior, , hypothalamus near the wall of the III ventricle. During, exposure to cold, heat gain center activates the motor, center and shivering occurs. Enormous heat is produced, during shivering due to severe muscular activities., PREVENTION OF HEAT LOSS, When the body is exposed to cold, heat gain center in, the posterior nucleus of hypothalamus is stimulated., It activates the sympathetic centers in posterior hypo, thalamus, resulting in cutaneous vasoconstriction and, decrease in blood flow. Due to decrease in cutaneous, blood flow, sweat secretion is decreased and heat loss, is prevented., , EFFECTS OF EXPOSURE TO, SEVERE COLD, Exposure of body to severe cold leads to death, if quick, remedy is not provided. The survival time depends, upon environmental temperature., If a person is exposed to ice cold water, i.e. 0°C, for 20 to 30 minutes, the body temperature falls below, 25°C (77°F) and the person can survive if he is placed, immediately in hot water tub with a temperature of 43°C
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Chapter 130 t Effects of Exposure to Cold and Heat 747, (110°F). Survival time at 9°C (28°F) is about 1 hour and, at 15.5°C (60°F) it is about 5 hours., Effects of exposure of body to extreme cold are:, 1. Loss of temperature regulating capacity, 2. Frostbite., LOSS OF TEMPERATURE, REGULATING CAPACITY, Temperature regulating capacity of hypothalamus is, affected when the body temperature decreases to about, 34.4°C (94°F). Hypothalamus totally looses the power, of temperature regulation when body temperature falls, below 25°C (77°F). Shivering does not occur., In addition to loss of hypothalamic function, the, metabolic activities are also suppressed. Sleep or coma, develops due to depression of central nervous system., FROSTBITE, Frostbite is the freezing of surface of the body when, it is exposed to cold. It occurs due to sluggishness of, blood flow. Most commonly, the exposed areas such, as ear lobes and digits of hands and feet are affected., Frostbite is common in mountaineers. Prolonged, exposure will lead to permanent damage of the cells,, followed by thawing and gangrene (death and decay, of tissues) formation., , EFFECTS OF EXPOSURE TO HEAT, Effects of exposure to heat are:, 1. Heat exhaustion, 2. Dehydration exhaustion, 3. Heat cramps, 4. Heatstroke (sunstroke)., HEAT EXHAUSTION, Heat exhaustion is the body’s response to excess, loss of water and salt through sweat, caused by expo, sure to hot environmental conditions. In fact, it is the, warning that body is getting too hot. Heat exhaustion, results in loss of consciousness and collapse. Before, the loss of consciousness, following warning signs, appear in the body:, i. Increased heart rate, ii. Increased cardiac output, iii. Dilatation of cutaneous blood vessels, iv. Increased moisture of the body, v. Fall in blood pressure, vi. Weakness and uneasiness, vii. Mild dyspnea., , DEHYDRATION EXHAUSTION, Prolonged exposure to heat results in dehydration. It is, due to excessive sweating. Dehydration leads to fall in, cardiac output and blood pressure. Collapse occurs if, treatment is not given immediately., HEAT CRAMPS, Severe painful cramps occur due to reduction in the, quantity of salts and water as a result of increased, sweating, during continuous exposure to heat., HEATSTROKE – SUNSTROKE, Heatstroke, Heatstroke is an abnormal type of hyperthermia, that occurs during exposure to extreme heat. It is, characterized by increase in body temperature above, 41°C (106°F), accompanied by some physical and, neurological symptoms. Compared to other effects of, exposure to heat such as heat exhaustion and heat, cramps, heatstroke is very severe and often becomes, fatal if not treated immediately. Hypothalamus loses the, power of regulating body temperature., Sunstroke, Sunstroke is the hyperthermia caused by prolonged, exposure to sun during summer in desert or tropical, areas., Persons Susceptible to Heatstroke or Sunstroke, People more susceptible to heatstroke or sunstroke, are:, i. Infants, ii. Old people with renal, cardiac or pulmonary, disorders, iii. People doing physical labor under sun, iv. Sportsmen involved in continuous sports, activities without break., Features, Common features of heatstroke or sunstroke are:, i. Nausea and vomiting, ii. Dizziness, iii. Headache, iv. Abdominal pain, v. Difficulty in breathing, vi. Vertigo
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748 Section 9 t Respiratory System and Environmental Physiology, vii. Confusion, viii. Muscle cramps and convulsions, ix. Paralysis, x. Unconsciousness., If immediate and vigorous treatment is not given,, damage of brain tissues occurs, resulting in coma and, death., Heatstroke and Humidity, Development of heatstroke depends upon humidity of, the environment. If the environmental air is completely, dry, exposure of body for several hours even to, a temperature of 54.4°C (130°F) does not cause, heatstroke. If air is 100% humid, even the temperature, of 41°C (106.8°F) causes heatstroke., Prevention, Heatstroke or sunstroke can be avoided by the following, measures:, , i. Avoiding dehydration by taking plenty of fluids, such as water or sports drinks, ii. Taking frequent breaks during work or sports, activity, iii. Wearing light clothes with hat., Treatment, Person affected by heatstroke or sunstroke must be, treated before the damage of organs. The subject, should be immediately moved from hot environment and, hospitalized as soon as possible. Immediate cooling, of the body is the usual treatment. The person must be, immersed in cold water or cold water may be sprayed, on the skin. If water supply is not sufficient, cooling, the head and neck of the subject should be done first., Ice cubes can be rubbed on head and neck. Ice packs, must be kept under armpits and groin. Cooling efforts, should be continued till the body temperature falls to, about 35°C.
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Artificial Respiration, , Chapter, , 131, , CONDITIONS WHEN ARTIFICIAL RESPIRATION IS REQUIRED, METHODS OF ARTIFICIAL RESPIRATION, , , , MANUAL METHODS, MECHANICAL METHODS, , CONDITIONS WHEN ARTIFICIAL, RESPIRATION IS REQUIRED, Artificial respiration is required whenever there is an, arrest of breathing, without cardiac failure. Arrest of, breathing occurs in the following conditions:, 1. Accidents, 2. Drowning, 3. Gas poisoning, 4. Electric shock, 5. Anesthesia., Stoppage of oxygen supply for 5 minutes causes, irreversible changes in tissues of brain, particularly, tissues of cerebral cortex. So, artificial respiration, (resuscitation) must be started quickly without any, delay, before the development of cardiac failure., Purpose of artificial respiration is to ventilate the, alveoli and to stimulate the respiratory centers., , METHODS OF ARTIFICIAL RESPIRATION, Methods of artificial respiration are of two types:, 1. Manual methods, 2. Mechanical methods., MANUAL METHODS, Manual methods of resuscitation can be applied quickly, without waiting for the availability of any mechanical, aids., Affected person must be provided with clear, air. Clothes around neck and chest regions must be, , loosened. Mouth, face and throat should be cleared of, mucus, saliva, foreign particles, etc. Tongue must be, drawn forward and it must be prevented from falling, posteriorly, which may cause airway obstruction., Manual methods are of two types:, i. Mouth-to-mouth method, ii. Holger Nielsen method., Mouth-to-mouth Method, The subject is kept in supine position and the, resuscitator (person who give resuscitation) kneels, at the side of the subject. By keeping the thumb on, subject’s mouth, the lower jaw is pulled downwards., Nostrils of the subject are closed with thumb and index, finger of the other hand., Resuscitator then takes a deep breath and exhales, into the subject’s mouth forcefully. Volume of exhaled, air must be twice the normal tidal volume. This expands, the subject’s lungs. Then, the resuscitator removes, his mouth from that of the subject. Now, a passive, expiration occurs in the subject due to elastic recoil of, the lungs. This procedure is repeated at a rate of 12 to, 14 times a minute, till normal respiration is restored., Mouth-to-mouth method is the most effective, manual method because, carbon dioxide in expired air, of the resuscitator can directly stimulate the respiratory, centers and facilitate the onset of respiration. Only, disadvantage is that the close contact between the, mouths of resuscitator and subject may not be acceptable for various reasons.
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750 Section 9 t Respiratory System and Environmental Physiology, Holger Nielsen Method or Back Pressure, Arm Lift Method, Subject is placed in prone position with head turned, to one side. Hands are placed under the cheeks with, flexion at elbow joint and abduction of arms at the, shoulders. Resuscitator kneels beside the head of, the subject. By placing the palm of the hands over the, back of the subject, the resuscitator bends forward with, straight arms (without flexion at elbow) and applies, pressure on the back of the subject., Weight of the resuscitator and pressure on back, of the subject compresses his chest and expels air, from the lungs. Later, the resuscitator leans back. At, the same time, he draws the subject’s arm forward by, holding it just above elbow., This procedure causes expansion of thoracic cage, and flow of air into the lungs. The movements are, repeated at the rate of 12 per minute, till the normal, respiration is restored., MECHANICAL METHODS, Mechanical methods of artificial respiration become, necessary when the subject needs artificial respiration, for long periods. It is essential during the respiratory, failure due to paralysis of respiratory muscles or any, other cause., Mechanical methods are of two types:, i. Drinker method, ii. Ventilation method., , airtight chamber, made of iron or steel. Subject is placed, inside this chamber with the head outside the chamber., By means of some pumps, the pressure inside the, chamber is made positive and negative alternately., During the negative pressure in the chamber, the, subject’s thoracic cage expands and inspiration occurs, and during positive pressure the expiration occurs., By using tank respirator, the patient can survive for, a longer time, even up to the period of one year till the, natural respiratory functions are restored., Ventilation Method, A rubber tube is introduced into the trachea of the patient, through the mouth. By using a pump, air or oxygen, is pumped into the lungs with pressure intermittently., When air is pumped, inflation of lungs and inspiration, occur. When it is stopped, expiration occurs and the, cycle is repeated. Apparatus used for ventilation is, called ventilator and it is mostly used to treat acute, respiratory failure., Ventilator is of two types:, a. Volume ventilator, b. Pressure ventilator., Volume ventilator, By volume ventilator, a constant volume of air is pumped, into the lungs of patients intermittently with minimum, pressure., , Drinker Method, , Pressure ventilator, , The machine used in this method is called iron lung, chamber or tank respirator. The equipment has an, , By pressure ventilator, air is pumped into the lungs of, subject with constant high pressure.
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Chapter, , Effects of Exercise, on Respiration, , 132, , INTRODUCTION, EFFECTS OF EXERCISE ON RESPIRATION, , , , , , , , PULMONARY VENTILATION, DIFFUSING CAPACITY FOR OXYGEN, CONSUMPTION OF OXYGEN, OXYGEN DEBT, VO2 MAX, RESPIRATORY QUOTIENT, , INTRODUCTION, Muscular exercise brings about a lot of changes on, various systems of the body. Degree of changes, depends upon the severity of exercise. Refer Chapter, 117 for types and severity of exercise., , EFFECTS OF EXERCISE, ON RESPIRATION, EFFECT ON PULMONARY VENTILATION, Pulmonary ventilation is the amount of air that enters, and leaves the lungs in 1 minute. It is the product of tidal, volume and respiratory rate. It is about 6 liter/minute,, with a normal tidal volume of 500 mL and respiratory, rate of 12/minute., During exercise, hyperventilation, which includes, increase in rate and force of respiration occurs. In, moderate exercise, respiratory rate increases to about, 30/minute and tidal volume increases to about 2,000 mL., Thus, the pulmonary ventilation increases to about 60 L/, minute during moderate exercise. In severe muscular, exercise, it rises still further up to 100 L/minute., Factors increasing pulmonary ventilation, during exercise, 1. Higher centers, 2. Chemoreceptors, , 3. Proprioceptors, 4. Body temperature, 5. Acidosis., 1. Higher Centers, Rate and depth of respiration increase during the onset, of exercise. Sometimes, before starting the exercise,, thought or anticipation of exercise itself increases, the rate and force of respiration. It is a psychic, phenomenon due to the activation of higher centers, like Sylvian cortex and motor cortex of brain. Higher, centers, in turn accelerate the respiratory processes by, stimulating respiratory centers., 2. Chemoreceptors, Chemoreceptors which are stimulated by exerciseinduced hypoxia and hypercapnea, send impulses to, the respiratory centers. Respiratory centers, in turn, increase the rate and force of respiration. Chemoreceptors are described in detail in Chapter 126., 3. Proprioceptors, Proprioceptors, which are activated during exercise, send, impulses to cerebral cortex through the somatic afferent, nerves. Cerebral cortex, in turn causes hyperventilation, by sending impulses to the medullary respiratory, centers. Refer Chapter 156 for proprioceptors.
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752 Section 9 t Respiratory System and Environmental Physiology, 4. Body Temperature, Body temperature which increases by muscular activity,, increases the ventilation by stimulating the respiratory, centers., 5. Acidosis, Acidosis developed during exercise also stimulates the, respiratory centers, resulting in hyperventilation., EFFECT ON DIFFUSING CAPACITY, FOR OXYGEN, Diffusing capacity for oxygen is about 21 mL/minute at, resting condition. It rises to 45 to 50 mL/minute during, moderate exercise because of increased blood flow, through pulmonary capillaries., EFFECT ON CONSUMPTION, OF OXYGEN, Oxygen consumed by the tissues, particularly the, skeletal muscles is greatly enhanced during exercise., Because of vasodilatation in muscles during exercise,, more amount of blood flows through the muscles and, more amount of oxygen diffuses into the muscles from, blood. The amount of oxygen utilized by the muscles is, directly proportional to the amount of oxygen available., EFFECT ON OXYGEN DEBT, Oxygen debt is the extra amount of oxygen required, by the muscles during recovery from severe muscular, exercise. After a period of severe muscular exercise,, , amount of oxygen consumed is greatly increased., Oxygen required is more than the quantity available to, the muscle. This much of oxygen is required not only for, the activity of the muscle but also for reversal of some, metabolic processes such as:, 1. Reformation of glucose from lactic acid, accumulated, during exercise, 2. Resynthesis of ATP and creatine phosphate, 3. Restoration of amount of oxygen dissociated from, hemoglobin and myoglobin., Thus, for the above reversal phenomena, an extra, amount of oxygen must be made available in the body, after severe muscular exercise. Oxygen debt is about, six times more than the amount of oxygen consumed, under resting conditions., EFFECT ON VO2 MAX, VO2 max is the amount of oxygen consumed under, maximal aerobic metabolism. It is the product of, maximal cardiac output and maximal amount of oxygen, consumed by the muscle., In a normal active and healthy male, the VO2 max is, 35 to 40 mL/kg body weight/minute. In females, it is 30, to 35 mL/kg body weight/minute. During exercise, VO2, max increases by 50%., EFFECT ON RESPIRATORY QUOTIENT, Respiratory quotient is the molar ratio of carbon dioxide, production to oxygen consumption. Refer Chapter 124, for details., Respiratory quotient in resting condition is 1.0 and, during exercise it increases to 1.5 to 2. However, at the, end of exercise, the respiratory quotient reduces to 0.5.
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Questions in Respiratory System and Environmental Physiology 753, , QUESTIONS IN RESPIRATORY SYSTEM AND ENVIRONMENTAL PHYSIOLOGY, , LONG QUESTIONS, 1. Describe the various movements of thoracic cage, and lungs during respiration., 2. Describe in detail the pulmonary circulation., 3. Give the definition and normal values of lung, volumes and lung capacities and explain the, measurement of the same., 4. Explain the transport of oxygen in blood., 5. Explain the transport of carbon dioxide in blood., 6. Describe the nervous regulation of respiration., 7. Describe the chemical regulation of respiration., 8. What is hypoxia? Describe the types, causes, and effects of hypoxia. Add a note on oxygen, therapy., 9. Describe the changes in the body at high altitude, and explain the acclimatization., 10. Describe in detail the respiratory and cardiovascular changes during exercise., , SHORT QUESTIONS, 1., 2., 3., 4., 5., 6., 7., 8., 9., 10., 11., 12., 13., 14., 15., 16., 17., 18., 19., 20., 21., , Respiratory unit., Respiratory membrane., Non-respiratory functions of respiratory tract., Physiological shunt., Characteristic features of pulmonary circulation., Collapsing tendency of lungs., Surfactant., Respiratory pressures., Compliance., Work of breathing., Spirometry., Measurement of functional residual capacity., Measurement of residual volume., Vital capacity., MBC or MVV., Forced expiratory volume., Plethysmography., Peak expiratory flow rate., Alveolar ventilation., Dead space., Ventilation perfusion ratio., , 22., 23., 24., 25., 26., 27., 28., 29., 30., 31., 32., 33., 34., 35., 36., 37., 38., 39., 40., 41., 42., 43., 44., 45., 46., 47., 48., 49., 50., 51., 52., 53., 54., 55., 56., 57., 58., 59., 60., 61., 62., , Respiratory quotient or respiratory exchange ratio., Alveolar air., Oxygen hemoglobin dissociation curve., Carbon dioxide dissociation curve., Bohr effect., Haldane effect., Chloride shift., Diffusing capacity., Exchange of gases between alveoli and blood., Exchange of gases between blood and tissues., Respiratory centers., Inspiratory ramp., Hering-Breuer reflex., Receptors of lungs taking part in control of, breathing., Chemoreceptors., Apnea., Hypoxia., Hyperventilation and hypoventilation., Hypercapnea and hypocapnea., Asphyxia., Dyspnea., Periodic breathing., Cyanosis., Oxygen toxicity (poisoning)., Carbon monoxide poisoning., Pneumothorax., Pneumonia., Pulmonary edema., Mountain sickness., Acclimatization., Effect of G force., Decompression sickness., Nitrogen narcosis., Effects of sudden exposure to cold., Effects of sudden exposure to heat., Heatstroke or sunstroke., Artificial respiration., Respiratory changes during exercise., Oxygen debt., VO2 max., Fetal respiration and first breath.
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Section, , 10, , 133., 134., 135., 136., 137., 138., 139., 140., 141., 142., 143., 144., 145., 146., 147., 148., , Nervous System, , Introduction to Nervous System .............................................................. 757, Neuron .................................................................................................... 759, Classification of Nerve Fibers ................................................................. 764, Properties of Nerve Fibers ...................................................................... 766, Degeneration and Regeneration of Nerve Fibers ................................... 770, Neuroglia ................................................................................................. 773, Receptors ................................................................................................ 775, Synapse .................................................................................................. 780, Neurotransmitters .................................................................................... 787, Reflex Activity .......................................................................................... 795, Spinal Cord ............................................................................................. 803, Somatosensory System and Somatomotor System ................................ 828, Physiology of Pain ................................................................................... 838, Brainstem ................................................................................................ 844, Thalamus ................................................................................................ 847, Internal Capsule ...................................................................................... 853
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149., 150., 151., 152., 153., 154., 155., 156., 157., 158., 159., 160., 161., 162., 163., 164., , Hypothalamus ......................................................................................... 855, Cerebellum .............................................................................................. 863, Basal Ganglia .......................................................................................... 878, Cerebral Cortex ....................................................................................... 884, Limbic System ......................................................................................... 898, Reticular Formation ................................................................................. 901, Preparations of Animals for Experimental Studies .................................. 906, Proprioceptors ......................................................................................... 908, Posture and Equilibrium .......................................................................... 913, Vestibular Apparatus ............................................................................... 919, Electroencephalogram (EEG) ................................................................. 929, Physiology of Sleep ................................................................................. 931, Epilepsy ................................................................................................... 935, Higher Intellectual Functions ................................................................... 937, Cerebrospinal Fluid (CSF) ...................................................................... 949, Autonomic Nervous System (ANS) ......................................................... 954
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Chapter, , Introduction, to Nervous System, , 133, , DIVISIONS OF NERVOUS SYSTEM, , , , CENTRAL NERVOUS SYSTEM, PERIPHERAL NERVOUS SYSTEM, , DIVISIONS OF NERVOUS SYSTEM, Nervous system controls all the activities of the body. It, is quicker than other control system in the body, namely, endocrine system. Primarily, nervous system is divided, into two parts:, 1. Central nervous system, 2. Peripheral nervous system., CENTRAL NERVOUS SYSTEM, Central nervous system (CNS) includes brain and, spinal cord. It is formed by neurons and supporting cells, called neuroglia. Structures of brain and spinal cord are, arranged in two layers, namely gray matter and white, matter. Gray matter is formed by nerve cell bodies and, , the proximal parts of nerve fibers, arising from nerve, cell body. White matter is formed by remaining parts of, nerve fibers., In brain, white matter is placed in the inner part and, gray matter is placed in the outer part. In spinal cord,, white matter is in the outer part and gray matter is in the, inner part., Brain is situated in the skull. It is continued as spinal, cord in the vertebral canal through the foramen magnum, of the skull bone. Brain and spinal cord are surrounded, by three layers of meninges called the outer dura mater,, middle arachnoid mater and inner pia mater., The space between arachnoid mater and pia mater, is known as subarachnoid space. This space is filled, with a fluid called cerebrospinal fluid. Brain and spinal, cord are actually suspended in the cerebrospinal fluid., Important parts of brain and segments of spinal cord are, shown in Figure 133.1., , FIGURE 133.1: Parts of central nervous system, , Parts of Brain, Brain consists of three major divisions:, 1. Prosencephalon
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758 Section 10 t Nervous System, , FIGURE 133.2: Parts of brain, , 2. Mesencephalon, 3. Rhombencephalon, 1. Prosencephalon, Prosencephalon is otherwise known as forebrain. It is, further divided into two parts:, i. Telencephalon, which includes cerebral hemi, spheres, basal ganglia, hippocampus and amygda, loid nucleus, ii. Diencephalon, consisting of thalamus, hypothala, mus, metathalamus and subthalamus., , 1. Somatic Nervous System, Somatic nervous system is concerned with somatic, functions. It includes the nerves supplying the skeletal, , muscles. Somatic nervous system is responsible for mus, cular activities and movements of the body (Fig. 133.3)., , 2. Autonomic Nervous System, Autonomic nervous system is concerned with regula, tion of visceral or vegetative functions. So, it is other, wise called vegetative or involuntary nervous system., Autonomic nervous system consists of two divisions,, sympathetic division and parasympathetic division., , 2. Mesencephalon, Mesencephalon is also known as midbrain., 3. Rhombencephalon, Rhombencephalon or hindbrain is subdivided into two, portions:, i. Metencephalon, formed by pons and cerebellum, ii. Myelencephalon or medulla oblongata (Fig. 133.2)., Midbrain, pons and medulla oblongata are together, called the brainstem., PERIPHERAL NERVOUS SYSTEM, Peripheral nervous system (PNS) is formed by neurons, and their processes present in all regions of the body., It consists of cranial nerves, arising from brain and, spinal nerves, arising from the spinal cord. It is again, divided into two subdivisions:, 1. Somatic nervous system, 2. Autonomic nervous system., , FIGURE 133.3: Organization of nervous system
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Chapter, , Neuron, , 134, , INTRODUCTION, CLASSIFICATION, , , , , DEPENDING UPON THE NUMBER OF POLES, DEPENDING UPON THE FUNCTION, DEPENDING UPON THE LENGTH OF AXON, , STRUCTURE, , , , , , , NERVE CELL BODY, DENDRITE, AXON, MYELIN SHEATH, NEURILEMMA, , NEUROTROPHINS – NEUROTROPHIC FACTORS, , , , NERVE GROWTH FACTOR, OTHER NEUROTROPHINS, , INTRODUCTION, Neuron or nerve cell is defined as the structural and, , functional unit of nervous system. Neuron is similar to, any other cell in the body, having nucleus and all the, organelles in cytoplasm. However, it is different from, other cells by two ways:, 1. Neuron has branches or processes called axon and, dendrites, , 2. Neuron does not have centrosome. So, it cannot, undergo division., , 1. Unipolar neurons, 2. Bipolar neurons, 3. Multipolar neurons., 1. Unipolar Neurons, Unipolar neurons are the neurons that have only one, pole. From a single pole, both axon and dendrite arise, (Fig. 134.1). This type of nerve cells is present only in, embryonic stage in human beings., , CLASSIFICATION OF NEURON, , 2. Bipolar Neurons, , Neurons are classified by three different methods., A. Depending upon the number of poles, B. Depending upon the function, C. Depending upon the length of axon., , Neurons with two poles are known as bipolar neurons., Axon arises from one pole and dendrites arise from the, other pole., , DEPENDING UPON THE NUMBER OF POLES, , Multipolar neurons are the neurons which have many, poles. One of the poles gives rise to axon and all other, , Based on the number of poles from which the nerve, fibers arise, neurons are divided into three types:, , 3. Multipolar Neurons, , poles give rise to dendrites.
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760 Section 10 t Nervous System, , STRUCTURE OF NEURON, Neuron is made up of three parts:, 1. Nerve cell body, 2. Dendrite, 3. Axon., Dendrite and axon form the processes of neuron, (Fig. 134.2). Dendrites are short processes and the, axons are long processes. Dendrites and axons are, usually called nerve fibers., NERVE CELL BODY, , FIGURE 134.1: Types of neuron, , DEPENDING UPON THE FUNCTION, On the basis of function, nerve cells are classified into, two types:, 1. Motor or efferent neurons, 2. Sensory or afferent neurons., 1. Motor or Efferent Neurons, Motor or efferent neurons are the neurons which carry, the motor impulses from central nervous system to, peripheral effector organs like muscles, glands, blood, vessels, etc. Generally, each motor neuron has a long, axon and short dendrites., 2. Sensory or Afferent Neurons, Sensory or afferent neurons are the neurons which, carry the sensory impulses from periphery to central, nervous system. Generally, each sensory neuron has a, short axon and long dendrites., , Nerve cell body is also known as soma or perikaryon. It, is irregular in shape. Like any other cell, it is constituted, by a mass of cytoplasm called neuroplasm, which is, covered by a cell membrane. The cytoplasm contains, a large nucleus, Nissl bodies, neurofibrils, mitochondria, and Golgi apparatus. Nissl bodies and neurofibrils are, found only in nerve cell and not in other cells., Nucleus, Each neuron has one nucleus, which is centrally placed, in the nerve cell body. Nucleus has one or two prominent, nucleoli. Nucleus does not contain centrosome. So, the, nerve cell cannot multiply like other cells., Nissl Bodies, Nissl bodies or Nissl granules are small basophilic, granules found in cytoplasm of neurons and are named, after the discoverer. These bodies are present in, soma and dendrite but not in axon and axon hillock., Nissl bodies are called tigroid substances, since, these bodies are responsible for tigroid or spotted, appearance of soma after suitable staining. Dendrites, are distinguished from axons by the presence of Nissl, granules under microscope., , DEPENDING UPON THE LENGTH OF AXON, Depending upon the length of axon, neurons are divided, into two types:, 1. Golgi type I neurons, 2. Golgi type II neurons., 1. Golgi Type I Neurons, Golgi type I neurons have long axons. Cell body of these, neurons is in different parts of central nervous system, and their axons reach the remote peripheral organs., 2. Golgi Type II Neurons, Neurons of this type have short axons. These neurons, are present in cerebral cortex and spinal cord., , FIGURE 134.2: Structure of a neuron
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Chapter 134 t Neuron 761, Nissl bodies are membranous organelles containing, ribosomes. So, these bodies are concerned with, synthesis of proteins in the neurons. Proteins formed in, soma are transported to the axon by axonal flow., Number of Nissl bodies varies with the condition of, the nerve. During fatigue or injury of the neuron, these, bodies fragment and disappear by a process called, chromatolysis. Granules reappear after recovery from, fatigue or after regeneration of nerve fibers., Neurofibrils, Neurofibrils are thread-like structures present in the, form of network in the soma and the nerve processes., Presence of neurofibrils is another characteristic feature, of the neurons. The neurofibrils consist of microfilaments, and microtubules., Mitochondria, Mitochondria are present in soma and in axon. As in, other cells, here also mitochondria form the powerhouse, of the nerve cell, where ATP is produced (Chapter 1)., Golgi Apparatus, Golgi apparatus of nerve cell body is similar to that of, other cells. It is concerned with processing and packing, of proteins into granules (Chapter 1)., DENDRITE, , Coverings of Nerve, The whole nerve is covered by tubular sheath, which is, formed by a areolar membrane. This sheath is called, epineurium. Each fasciculus is covered by perineurium, and each nerve fiber (axon) is covered by endoneurium, (Fig. 134.3)., Internal Structure of Axon – Axis Cylinder, Axon has a long central core of cytoplasm called, axoplasm. Axoplasm is covered by the tubular sheathlike membrane called axolemma. Axolemma is the, continuation of the cell membrane of nerve cell body., Axoplasm along with axolemma is called the axis, cylinder of the nerve fiber (Fig. 134.4)., Axoplasm contains mitochondria, neurofibrils and, axoplasmic vesicles. Because of the absence of Nissl, bodies in the axon, proteins necessary for the nerve, fibers are synthesized in the soma and not in axoplasm., After synthesis, the protein molecules are transported, from soma to axon, by means of axonal flow. Some, neurotransmitter substances are also transported by, axonal flow from soma to axon., Axis cylinder of the nerve fiber is covered by a, membrane called neurilemma (see below)., Non-myelinated Nerve Fiber, Nerve fiber described above is the non-myelinated, nerve fiber, which is not covered by myelin sheath., , Dendrite is the branched process of neuron and it is, branched repeatedly. Dendrite may be present or, absent. If present, it may be one or many in number., Dendrite has Nissl granules and neurofibrils., Dendrite transmits impulses towards the nerve cell, body. Usually, the dendrite is shorter than axon., AXON, Axon is the longer process of nerve cell. Each neuron, has only one axon. Axon arises from axon hillock of the, nerve cell body and it is devoid of Nissl granules. Axon, extends for a long distance away from the nerve cell, body. Length of longest axon is about 1 meter., Axon transmits impulses away from the nerve cell, body., Organization of Nerve, Each nerve is formed by many bundles or groups of, nerve fibers. Each bundle of nerve fibers is called a, fasciculus., , FIGURE 134.3: Cross section of a nerve
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762 Section 10 t Nervous System, Functions of Myelin Sheath, 1. Faster conduction, Myelin sheath is responsible for faster conduction of, impulse through the nerve fibers. In myelinated nerve, fibers, the impulses jump from one node to another, node. This type of transmission of impulses is called, saltatory conduction (Chapter 136)., 2. Insulating capacity, Myelin sheath has a high insulating capacity. Because, of this quality, myelin sheath restricts the nerve impulse, within single nerve fiber and prevents the stimulation of, neighboring nerve fibers., FIGURE 134.4: A. Myelinated nerve fiber;, B. Non-myelinated nerve fiber., , Myelinated Nerve Fiber, Nerve fiber which is insulated by myelin sheath is called, myelinated nerve fibers., MYELIN SHEATH, Myelin sheath is a thick lipoprotein sheath that insulates, the myelinated nerve fiber. Myelin sheath is not a, continuous sheath. It is absent at regular intervals. The, area where myelin sheath is absent is called node of, Ranvier. Segment of the nerve fiber between two nodes, is called internode. Myelin sheath is responsible for, white color of nerve fibers., Chemistry of Myelin Sheath, Myelin sheath is formed by concentric layers of proteins,, alternating with lipids. The lipids are cholesterol, lecithin, and cerebroside (sphingomyelin)., Formation of Myelin Sheath – Myelinogenesis, Formation of myelin sheath around the axon is called, the myelinogenesis. It is formed by Schwann cells in, neurilemma. In the peripheral nerve, the myelinogenesis, starts at 4th month of intrauterine life. It is completed, only in the second year after birth., Before myelinogenesis, Schwann cells of the neurilemma are very close to axolemma, as in the case, of unmyelinated nerve fiber. The membrane of the, Schwann cell is double layered., Schwann cells wrap up and rotate around the axis, cylinder in many concentric layers. The concentric layers, fuse to produce myelin sheath but cytoplasm of the cells, is not deposited. Outermost membrane of Schwann cell, remains as neurilemma. Nucleus of these cells remains, in between myelin sheath and neurilemma., , NEURILEMMA, Neurilemma is a thin membrane, which surrounds the, axis cylinder. It is also called neurilemmal sheath or, sheath of Schwann. It contains Schwann cells, which, have flattened and elongated nuclei. Cytoplasm is thin, and modified to form the thin sheath of neurilemma., One nucleus is present in each internode of the, axon. Nucleus is situated between myelin sheath and, neurilemma., In non-myelinated nerve fiber, the neurilemma, surrounds axolemma continuously. In myelinated, nerve fiber, it covers the myelin sheath. At the node of, Ranvier (where myelin sheath is absent), neurilemma, invaginates and runs up to axolemma in the form of a, finger-like process., Functions of Neurilemma, In non-myelinated nerve fiber, the neurilemma serves, as a covering membrane. In myelinated nerve fiber,, it is necessary for the formation of myelin sheath, (myelinogenesis). Neurilemma is absent in central, nervous system. So, the neuroglial cells called, oligodendroglia are responsible for myelinogenesis in, central nervous system., , NEUROTROPHINS –, NEUROTROPHIC FACTORS, Neurotrophins or neurotrophic factors are the protein, substances, which play an important role in growth and, functioning of nervous tissue., Source of Secretion, Neurotrophins are secreted by many tissues in the body,, particularly muscles, neuroglial cells called astrocytes, and neurons.
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Chapter 134 t Neuron 763, Functions, Neurotrophins:, 1. Facilitate initial growth and development of nerve, cells in central and peripheral nervous system, 2. Promote survival and repair of the nerve cells, 3. Play an important role in the maintenance of nervous, tissue and neural transmission., Recently, it is found that neurotrophins are, capable of making the damaged neurons regrow their, processes in vitro and in animal models. This indicates, the possibilities of reversing the devastating symptoms, of nervous disorders like Parkinson disease and, Alzheimer disease., , Commercial preparations of neurotrophins are, used for the treatment of some neural diseases., Mode of Action, Neurotrophins act via neurotrophin receptors, which, are situated at the nerve terminals and nerve cell body., Neurotrophins bind with receptors and initiate the, phosphorylation of tyrosine kinase., Types, Nerve growth factor (NGF) was the first protein, substance identified as neurotrophin. Now, many types, of neurotophic factors are identified., NERVE GROWTH FACTOR, , 3. NGF plays an important role in treating many, nervous disorders such as Alzheimer disease,, neuron degeneration in aging and neuron regeneration in spinal cord injury., OTHER NEUROTROPHINS, 1. Brain-derived Neurotrophic Growth Factor, Brain-derived neurotrophic growth factor (BDGF) was, first discovered in the brain of pig. Now it is found in human, brain and human sperm. BDGF promotes the survival, of sensory and motor neurons, arising from embryonic, neural crest. It also protects the sensory neurons, in peripheral nervous system and motor neurons of, pyramidal system. It enhances the growth of cholinergic,, dopaminergic and optic nerves. It is suggested that, BDGF may regulate synaptic transmission., Commercial preparation is used to treat motor, neuron diseases., , 2. Ciliary Neurotrophic Factor (CNTF), CNTF is secreted in peripheral nerves, ocular muscles, and cardiac muscle. It protects neurons of ciliary, ganglion and motor neurons., 3. Glial Cell Line-derived Neurotrophic, Factor (GNDF), , Nerve growth factor (NGF) is a neurotrophin found in, many peripheral tissues., , GDNF is found in neuroglial cells. It has a potent, protective action on dopaminergic neurons. It is used, for the treatment of Parkinson disease., , Chemistry, , 4. Fibroblast Growth Factor (FGF), , NGF is a peptide with 118 amino acids. Each molecule, of NGF is made up of two α-subunits, two β-subunits, and two γ-subunits. Only the β-subunits have nerve, growth-stimulating activity., , FGF was first discovered as growth factor promoting, the fibroblastic growth. It is also known to protect the, neurons., , Functions, , Neurotrophin-3 (NT-3) acts on γ-motor neurons, sympathetic neurons and neurons from sensory organs., It also regulates the release of neurotransmitter from, neuromuscular junction., NT-3 is useful for the treatment of motor axonal, neuropathy and diabetic neuropathy., Recently, few more substances belonging to the, neurotrophin family such as NT-4, NT-5 and leukemiainhibiting factor are identified. NT-4 and NT-5 act on, sympathetic neurons, sensory neurons and motor, neurons., , 1. NGF promotes early growth and development, of neurons. Its major action is on sympathetic, and sensory neurons, particularly the neurons, concerned with pain. Because of its major action on, sympathetic neurons, it is also called sympathetic, NGF. NGF also promotes the growth of cholinergic, neurons in cerebral hemispheres., 2. Commercial preparation of NGF extracted from, snake venom and submaxillary glands of male mouse, is used to treat sympathetic neuron diseases., , 5. Neurotrophin-3 (NT-3)
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Chapter, , Classification of, Nerve Fibers, , 135, , BASIS OF CLASSIFICATION, , , , , , , , DEPENDING UPON STRUCTURE, DEPENDING UPON DISTRIBUTION, DEPENDING UPON ORIGIN, DEPENDING UPON FUNCTION, DEPENDING UPON SECRETION OF NEUROTRANSMITTER, DEPENDING UPON DIAMETER AND CONDUCTION OF IMPULSE, , BASIS OF CLASSIFICATION, , 2. DEPENDING UPON DISTRIBUTION, , Nerve fibers are classified by six different methods., The basis of classification differs in each method. Differ, ent methods of classification are listed in Box 135.1., , Nerve fibers are classified into two types, on the basis, of distribution:, i. Somatic Nerve Fibers, , BOX 135.1: Different methods to classify nerve fibers, Classification of nerve fibers, 1., 2., 3., 4., 5., 6., , Depending upon structure, Depending upon distribution, Depending upon origin, Depending upon function, Depending upon secretion of neurotransmitter, Depending upon diameter and conduction of impulse, (ErlangerGasser classification), , 1. DEPENDING UPON STRUCTURE, Based on structure, nerve fibers are classified into two, types:, i. Myelinated Nerve Fibers, Myelinated nerve fibers are the nerve fibers that are, covered by myelin sheath., , Somatic nerve fibers supply the skeletal muscles of the, body., ii. Visceral or Autonomic Nerve Fibers, Autonomic nerve fibers supply the various internal, , organs of the body., , 3. DEPENDING UPON ORIGIN, On the basis of origin, nerve fibers are divided into two, types:, i. Cranial Nerve Fibers, Nerve fibers arising from brain are called cranial, nerve fibers., ii. Spinal Nerve Fibers, Nerve fibers arising from spinal cord are called spinal, nerve fibers., , ii. Non-myelinated Nerve Fibers, Nonmyelinated nerve fibers are the nerve fibers which, are not covered by myelin sheath., , 4. DEPENDING UPON FUNCTION, Functionally, nerve fibers are classified into two types:
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Chapter 135 t Classification of Nerve Fibers 765, TABLE 135.1: Types of nerve fibers, , i. Sensory Nerve Fibers, Sensory nerve fibers carry sensory impulses from, different parts of the body to the central nervous system., These nerve fibers are also known as afferent nerve, fibers., , Type, , Diameter, (µ), , Velocity of conduction, (meter/second), , A alpha, , 12 to 24, , 70 to 120, , A beta, , 6 to 12, , 30 to 70, , A gamma, , 5 to 6, , 15 to 30, , ii. Motor Nerve Fibers, , A delta, , 2 to 5, , 12 to 15, , Motor nerve fibers carry motor impulses from central, nervous system to different parts of the body. These, nerve fibers are also called efferent nerve fibers., , B, , 1 to 2, , C, , < 1.5, , 5. DEPENDING UPON SECRETION, OF NEUROTRANSMITTER, Depending upon the neurotransmitter substance, secreted, nerve fibers are divided into two types:, i. Adrenergic Nerve Fibers, Adrenergic nerve fibers secrete noradrenaline., ii. Cholinergic Nerve Fibers, Cholinergic nerve fibers secrete acetylcholine., 6. DEPENDING UPON DIAMETER AND, CONDUCTION OF IMPULSE, (ERLANGER-GASSER CLASSIFICATION), Erlanger and Gasser classified the nerve fibers into, three major types, on the basis of diameter (thickness), of the fibers and velocity of conduction of impulses:, , 3 to 10, 0.5 to 2, , i. Type A nerve fibers, ii. Type B nerve fibers, iii. Type C nerve fibers., Among these fibers, type A nerve fibers are, the thickest fibers and type C nerve fibers are the, thinnest fibers. Type C fibers are also known as Type, IV fibers. Except type C fibers, all the nerve fibers are, myelinated., Type A nerve fibers are divided into four types:, a., b., c., d., , Type A alpha or Type I nerve fibers, Type A beta or Type II nerve fibers, Type A gamma nerve fibers, Type A delta or Type III nerve fibers., , Velocity of Impulse, Velocity of impulse through a nerve fiber is directly, proportional to the thickness of the fiber. Different types, of nerve fibers along with diameter and velocity of, conduction are given in Table 135.1.
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Properties of Nerve Fibers, , Chapter, , 136, , EXCITABILITY, , , , , ACTION POTENTIAL OR NERVE IMPULSE, ELECTROTONIC POTENTIAL OR LOCAL POTENTIAL, VOLTAGE CLAMPING, , CONDUCTIVITY, , , , MECHANISM OF CONDUCTION OF ACTION POTENTIAL, CONDUCTION THROUGH MYELINATED NERVE FIBER –, SALTATORY CONDUCTION, , REFRACTORY PERIOD, , , , , , , , TYPES OF REFRACTORY PERIOD, , SUMMATION, ADAPTATION, INFATIGABILITY, ALL-OR-NONE LAW, , EXCITABILITY, Excitability is defined as the physiochemical change, that occurs in a tissue when stimulus is applied., Stimulus is defined as an external agent, which, produces excitability in the tissues. Different types of, stimulus, qualities of stimulus and strength-duration, curve are explained in Chapter 30. Chronaxie is an, important parameter to determine the condition of nerve, fiber. Clinically, the damage of nerve fiber is determined, by measuring the chronaxie. It is measured by chronaxie, meter., Nerve fibers have a low threshold for excitation than, the other cells., Response Due to Stimulation of Nerve Fiber, When a nerve fiber is stimulated, based on the strength, of stimulus, two types of response develop:, 1. Action potential or nerve impulse, Action potential develops in a nerve fiber when it is, stimulated by a stimulus with adequate strength. Adequate strength of stimulus, necessary for producing the, , action potential in a nerve fiber is known as threshold or, minimal stimulus. Action potential is propagated., 2. Electrotonic potential or local potential, When the stimulus with subliminal strength is applied,, only electrotonic potential develops and the action, potential does not develop. Electrotonic potential is nonpropagated., Cathelectrotonic and Anelectrotonic Potentials, While recording electrical potential in a nerve fiber, two, electrodes, namely cathode and anode are used. The, potential change that is produced at cathode is called, cathelectrotonic potential. The potential that is developed at anode is known as anelectrotonic potential., Only the cathelectrotonic potential can be transformed into electrotonic potential or action potential., ACTION POTENTIAL OR NERVE IMPULSE, Action potential in a nerve fiber is similar to that in a, muscle, except for some minor differences (Table, 136.1). Action potential in a skeletal muscle fiber is, described in Chapter 31.
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Chapter 136 t Properties of Nerve Fibers 767, TABLE 136.1: Differences between electrical potential, in nerve fiber and muscle fiber, Nerve fiber, , Skeletal muscle, fiber, , Resting membrane, potential, , –70 mV, , –90 mV, , Firing level, , –55 mV, , –75 mV, , End of depolarization, , +35 mV, , +55 mV, , Event, , Properties of Electrotonic Potential, 1. Electrotonic potential is non-propagated, 2. It does not obey all-or-none law. If the intensity, of the stimulus is increased gradually every time,, there is increase in the amplitude till the firing level, is reached, i.e. at 15 mV., VOLTAGE CLAMPING, The term ‘voltage clamping’ refers to an experimental, method that uses electrodes to alter and control the, membrane potential. Voltage clamp technique is a, modified patch clamp technique (Chapter 31) applied, to nerve fibers. It is used to measure the ionic current, across the membrane of nerve fiber by fixing the, membrane potential at a desired voltage., Principle of Voltage Clamping, , Resting membrane potential in the nerve fiber is, –70 mV. The firing level is at –55 mV. Depolarization, ends at +35 mV (Fig. 136.1). Usually, the action, potential starts in the initial segment of nerve fiber., , Normally, the voltage-gated ion channels open and, close in response to positive or negative charge within, the cell. In order to understand the movement of ions, across the membrane (ion flux), it would be necessary, to eliminate the other variable, i.e. the differences in the, membrane potential. It is because of two reasons:, 1. Both the ion flux and membrane potential are interrelated, 2. Differences in membrane potential would lead to, differences in ion flux., So the membrane potential is fixed (clamped) at a, specific level by using voltage clamp. It allows study of, the ion flux through ionic channels at specific membrane, potentials., , Properties of Action Potential, , Equipment for Voltage Clamping, , Properties of action potential are given in Chapter 31., , Voltage clamp equipment has three units:, 1. Recording amplifier, 2. Current generator, 3. Feedback amplifier., 1. Recording amplifier measures the voltage of, membrane potential. Two recording electrodes, namely, the extracelluar electrode and intracellular electrode are connected to this amplifier. Extracellular electrode is placed on the outer surface of, the nerve membrane and the intracellular electrode, is inserted into the nerve fiber., 2. Current generator or signal generator is used, to control the resting membrane potential of the, nerve fiber. The current signals generated by this, instrument are passed into the nerve fiber through a, current electrode., , FIGURE 136.1: Action potential in nerve fiber, , ELECTROTONIC POTENTIAL OR, LOCAL POTENTIAL, Electrotonic potential or local potential is a non-propagated local response that develops in the nerve fiber, when a subliminal stimulus is applied. Subliminal, or subthreshold stimulus does not produce action, potential. But, it alters the resting membrane potential, and produces slight depolarization for about 7 mV. This, slight depolarized state is called electrotonic potential., Firing level is reached only if depolarization occurs up, to 15 mV. Then only action potential can develop., Electrotonic potential is a graded potential (Refer, to Chapter 31).
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768 Section 10 t Nervous System, areas. Like this, depolarization travels throughout the, nerve fiber. Depolarization is followed by repolarization., CONDUCTION THROUGH MYELINATED, NERVE FIBER – SALTATORY CONDUCTION, Saltatory conduction is the form of conduction of nerve, impulse in which, the impulse jumps from one node to, another. Conduction of impulse through a myelinated, nerve fiber is about 50 times faster than through a nonmyelinated fiber. It is because the action potential jumps, from one node to another node of Ranvier instead of, travelling through the entire nerve fiber (Fig. 136.3)., Mechanism of Saltatory Conduction, , FIGURE 136.2: Voltage clamping, , Myelin sheath is not permeable to ions. So, the entry of, sodium from extracellular fluid into nerve fiber occurs, only in the node of Ranvier, where the myelin sheath is, absent. It causes depolarization in the node and not in, the internode. Thus, depolarization occurs at successive, , 3. Feedback amplifier receives feedback inputs from, recording amplifier and current generator and, accordingly modifies the current signals that are, sent into the nerve fiber (Fig. 136.2)., Thus, by voltage clamping, it is possible to maintain, the constant membrane potential at a desired voltage., Nerve Fibers Used for Voltage Clamping, Earlier, the voltage clamp tests were done on the giant, axon of the squid Loligo, whose size facilitates such, tests. Then the investigations were done on the neurons, of small mammals. Nowadays, the tests are done on the, human nerve fibers obtained from surgical procedures., , CONDUCTIVITY, Conductivity is the ability of nerve fibers to transmit, the impulse from the area of stimulation to the other, areas. Action potential is transmitted through the nerve, fiber as nerve impulse. Normally in the body, the action, potential is transmitted through the nerve fiber in only, one direction. However, in experimental conditions, when, the nerve is stimulated, the action potential, travels through the nerve fiber in either direction., MECHANISM OF CONDUCTION, OF ACTION POTENTIAL, Depolarization occurs first at the site of stimulation in the, nerve fiber. It causes depolarization of the neighboring, , FIGURE 136.3: Mode of conduction through nerve fibers, A. Non-myelinated nerve fiber: continuous conduction., B. Myelinated nerve fiber: saltatory conduction (impulse jumps, from node to node). AP = Action potential.
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Chapter 136 t Properties of Nerve Fibers 769, nodes. So, the action potential jumps from one node to, another. Hence, it is called saltatory conduction (saltare, = jumping)., , REFRACTORY PERIOD, Refractory period is the period at which the nerve does, not give any response to a stimulus., TYPES OF REFRACTORY PERIOD, Refractory period is of two types:, 1. Absolute Refractory Period, Absolute refractory period is the period during which, the nerve does not show any response at all, whatever, may be the strength of stimulus., 2. Relative Refractory Period, It is the period, during which the nerve fiber shows, response, if the strength of stimulus is increased to, maximum., Absolute refractory period corresponds to the, period from the time when firing level is reached till, the time when one third of repolarization is completed., Relative refractory period extends through rest of the, repolarization period., , SUMMATION, When one subliminal stimulus is applied, it does not, produce any response in the nerve fiber because, the, subliminal stimulus is very weak. However, if two or more, , subliminal stimuli are applied within a short interval of, about 0.5 millisecond, the response is produced. It is, because the subliminal stimuli are summed up together, to become strong enough to produce the response., This phenomenon is known as summation., , ADAPTATION, While stimulating a nerve fiber continuously, the excitability of the nerve fiber is greater in the beginning. Later, the response decreases slowly and finally the nerve fiber, does not show any response at all. This phenomenon, is known as adaptation or accommodation., Cause for Adaptation, When a nerve fiber is stimulated continuously, depolarization occurs continuously. Continuous depolarization inactivates the sodium pump and increases the, efflux of potassium ions., , INFATIGABILITY, Nerve fiber cannot be fatigued, even if it is stimulated, continuously for a long time. The reason is that nerve, fiber can conduct only one action potential at a time., At that time, it is completely refractory and does not, conduct another action potential., , ALL-OR-NONE LAW, All-or-none law states that when a nerve is stimulated, by a stimulus it gives maximum response or does not, give response at all. Refer Chapter 90 for more details, on all-or-none law.
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Degeneration and, Regeneration of, Nerve Fibers, , Chapter, , 137, , INTRODUCTION, DEGREES OF INJURY, , , , , , , FIRST DEGREE, SECOND DEGREE, THIRD DEGREE, FOURTH DEGREE, FIFTH DEGREE, , DEGENERATIVE CHANGES IN THE NEURON, , , , , WALLERIAN DEGENERATION, RETROGRADE DEGENERATION, TRANSNEURONAL DEGENERATION, , REGENERATION OF NERVE FIBER, , , , CRITERIA FOR REGENERATION, STAGES OF REGENERATION, , INTRODUCTION, When a nerve fiber is injured, various changes occur in, the nerve fiber and nerve cell body. All these changes, are together called the degenerative changes., Causes for Injury, Injury to nerve fiber occurs due to following causes:, 1. Obstruction of blood flow, 2. Local injection of toxic substances, 3. Crushing of nerve fiber, 4. Transection of nerve fiber., , DEGREES OF INJURY, Sunderland had classified the injury to nerve fibers into, , five categories depending upon the order of severity., FIRST DEGREE, , First degree injury is the most common type of injury, to the nerves. It is caused by applying pressure over, , a nerve for a short period leading to occlusion of blood, flow and hypoxia., By first degree of injury, axon is not destroyed but, mild demyelination occurs. It is not a true degeneration., Axon looses the function temporarily for a short time,, which is called conduction block. The function returns, within few hours to few weeks. First degree of injury is, called Seddon neuropraxia., SECOND DEGREE, Second degree is due to the prolonged severe pres, sure, which causes Wallerian degeneration (see, below). However, the endoneurium is intact. Repair and, restoration of function take about 18 months. Second, degree of injury is called axonotmesis., THIRD DEGREE, In this case, the endoneurium is interrupted. Epineurium and perineurium are intact. After degeneration,, the recovery is slow and poor or incomplete. Third, fourth, and fifth degrees of injury are called neurotmesis.
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Chapter 137 t Degeneration and Regeneration of Nerve Fibers 771, FOURTH DEGREE, This type of injury is more severe. Epineurium and, perineurium are also interrupted. Fasciculi of nerve, fibers are disturbed and disorganized. Regeneration is, poor or incomplete., FIFTH DEGREE, Fifth degree of injury involves complete transaction, of the nerve trunk with loss of continuity. Useful, regeneration is not possible unless the cut ends are, rearranged and approximated quickly by surgery., , DEGENERATIVE CHANGES, IN THE NEURON, Degeneration refers to deterioration or impairment, or pathological changes of an injured tissue. When, a peripheral nerve fiber is injured, the degenerative, changes occur in the nerve cell body and the nerve fiber, of same neuron and the adjoining neuron., Accordingly, degenerative changes are classified, into three types:, 1. Wallerian degeneration, 2. Retrograde degeneration, 3. Transneuronal degeneration., WALLERIAN DEGENERATION, OR ORTHOGRADE DEGENERATION, Wallerian degeneration is the pathological change that, occurs in the distal cut end of nerve fiber (axon). It, is named after the discoverer Waller. It is also called, orthograde degeneration. Wallerian degeneration starts, within 24 hours of injury. Change occurs throughout the, length of distal part of nerve fiber simultaneously., Changes in Nerve, i. Axis cylinder swells and breaks up into small pieces., After few days, the broken pieces appear as debris, in the space occupied by axis cylinder (Fig. 137.1)., ii. Myelin sheath is slowly disintegrated into fat, droplets. The changes in myelin sheath occur from, 8th to 35th day., iii. Neurilemmal sheath is unaffected, but the Schwann, cells multiply rapidly. Macrophages invade from, outside and remove the debris of axis cylinder and, fat droplets of disintegrated myelin sheath. So,, the neurilemmal tube becomes empty. Later it is, filled by the cytoplasm of Schwann cell. All these, , FIGURE 137.1: Degeneration and regeneration of nerve fiber, , changes take place for about 2 months from the day, of injury., RETROGRADE DEGENERATION, Retrograde degeneration is the pathological changes,, which occur in the nerve cell body and axon proximal to, the cut end.
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772 Section 10 t Nervous System, Changes in Nerve Cell Body, , CRITERIA FOR REGENERATION, , Changes in the nerve cell body commence within 48, hours after the section of nerve. The changes are:, i. First, the Nissl granules disintegrate into fragments, by chromatolysis, ii. Golgi apparatus is disintegrated, iii. Nerve cell body swells due to accumulation of fluid, and becomes round, iv. Neurofibrils disappear followed by displacement of, the nucleus towards the periphery, v. Sometimes, the nucleus is extruded out of the cell., In this case, death of the neuron occurs and regeneration of the injured nerve is not possible., , Regeneration is possible only if certain criteria are, fulfilled by the degenerated nerve fiber:, 1. Gap between the cut ends of the nerve should not, exceed 3 mm, 2. Neurilemma should be present; as neurilemma is, absent in CNS, the regeneration of nerve does not, occur in CNS, 3. Nucleus must be intact; if it is extruded from nerve, cell body, the nerve is atrophied and the regeneration does not occur, 4. Two cut ends should remain in the same line. Regeneration does not occur if any one end is moved, away., , Changes in Axon Proximal to Cut End, , STAGES OF REGENERATION, , In the axon, changes occur only up to first node of, Ranvier from the site of injury. Degenerative changes, that occur in proximal cut end of axon are similar to, those changes occurring in distal cut end of the nerve, fiber., , 1. First, some pseudopodia like extensions grow from, the proximal cut end of the nerve. These extensions, are called fibrils or regenerative sprouts. The, number of fibrils is up to 100., 2. Fibrils move towards the distal cut end of the nerve, fiber, 3. Some of the fibrils enter the neurilemmal tube of, distal end and form axis cylinder, 4. Schwann cells line up in the neurilemmal tube and, actually guide the fibrils into the tube. Schwann, cells also synthesize nerve growth factors, which, attract the fibrils form proximal segment., 5. Axis cylinder is fully established inside the, neurilemmal tube. These processes are completed, in about 3 months after injury., 6. Myelin sheath is formed by Schwann cells slowly., Myelination is completed in 1 year., 7. Diameter of the nerve fiber gradually increases., However, the degenerated nerve fiber obtains only, 80% of original diameter. Newly formed internodes, are also shorter than the original ones., 8. In the nerve cell body, first the Nissl granules, appear followed by Golgi apparatus, 9. Cell looses the excess fluid; nucleus occupies the, central portion, 10. Though anatomical regeneration occurs in the nerve,, functional recovery occurs after a long period., , TRANSNEURONAL DEGENERATION, If an afferent nerve fiber is cut, the degenerative changes occur in the neuron with which the afferent nerve, fiber synapses. It is called transneuronal degeneration., Examples:, i. Chromatolysis in the cells of lateral geniculate body, occurs due to sectioning of optic nerve, ii. Degeneration of cells in dorsal horn of spinal cord, occurs when the posterior nerve root is cut, iii. Degeneration of cells in ventral horn of spinal cord, occurs when there is tumor in cerebral cortex., , REGENERATION OF NERVE FIBER, The term regeneration refers to regrowth of lost or, destroyed part of a tissue. The injured and degenerated, nerve fiber can regenerate. It starts as early as 4th day, after injury, but becomes more effective only after 30, days and is completed in about 80 days.
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Chapter, , Neuroglia, , 138, , DEFINITION, CLASSIFICATION, CENTRAL NEUROGLIAL CELLS, , , , , ASTROCYTES, MICROGLIA, OLIGODENDROCYTES, , PERIPHERAL NEUROGLIAL CELLS, , , , SCHWANN CELLS, SATELLITE CELLS, , DEFINITION, Neuroglia or glia (glia = glue) is the supporting cell of, the nervous system. Neuroglial cells are non-excitable, and do not transmit nerve impulse (action potential). So,, these cells are also called non-neural cells or glial cells., When compared to the number of neurons, the number, of glial cells is 10 to 15 times greater. Neuroglial cells, play an important role in the reaction of nerve during, infection. Most commonly, neuroglial cells constitute the, site of tumors in nervous system., , CLASSIFICATION OF, NEUROGLIAL CELLS, Neuroglial cells are distributed in central nervous, system (CNS) as well as peripheral nervous system, (PNS). Accordingly the neuroglial cells are classified, into two types:, A. Central neuroglial cells, B. Peripheral neuroglial cells., , CENTRAL NEUROGLIAL CELLS, Neuroglial cells in CNS are of three types:, 1. Astrocytes, , 2. Microglia, 3. Oligodendrocytes., ASTROCYTES, Astrocytes are star-shaped neuroglial cells present, in all the parts of the brain (Fig. 138.1). Two types of, astrocytes are found in human brain:, i. Fibrous astrocytes, ii. Protoplasmic astrocytes., Fibrous Astrocytes, Fibrous astrocytes occupy mainly the white matter., Few fibrous astrocytes are seen in gray matter also., The processes of these cells cover the nerve cells and, synapses. This type of astrocytes play an important, role in the formation of blood-brain barrier by sending, processes to the blood vessels of brain, particularly, the capillaries, forming tight junction with capillary, membrane. Tight junction in turn forms the blood-brain, barrier., Protoplasmic Astrocytes, Protoplasmic astrocytes are present mainly in gray, matter. The processes of neuroglia run between nerve, cell bodies.
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774 Section 10 t Nervous System, ii. Migrate to the injured or infected area of CNS, and act as miniature macrophages., OLIGODENDROCYTES, Oligodendrocytes are the neuroglial cells, which produce myelin sheath around the nerve fibers in CNS., Oligodentrocytes are also called oligodendroglia. Oligodendrocytes have only few processes, which are short., Functions of Oligodendrocytes, Oligodendrocytes:, i. Provide myelination around the nerve fibers in, CNS where Schwann cells are absent, ii. Provide support to the CNS neurons by forming, a semi-stiff connective tissue between the, neurons., FIGURE 138.1: Neuroglial cells in CNS, , Functions of Astrocytes, Astrocytes:, i. Twist around the nerve cells and form the, supporting network in brain and spinal cord, ii. Form the blood-brain barrier and thereby, regulate the entry of substances from blood into, brain tissues (Chapter 163), iii. Maintain the chemical environment of ECF, around CNS neurons, iv. Provide calcium and potassium and regulate, neurotransmitter level in synapses, v. Regulate recycling of neurotransmitter during, synaptic transmission., MICROGLIA, Microglia are the smallest neuroglial cells. These cells, are derived from monocytes and enter the tissues of, nervous system from blood. These phagocytic cells, migrate to the site of infection or injury and are often, called the macrophages of CNS., , PERIPHERAL NEUROGLIAL CELLS, Neuroglial cells in PNS are of two types:, 1. Schwann cells, 2. Satellite cells., SCHWANN CELLS, Schwann cells are the major glial cells in PNS (Refer to, Chapter 134)., Functions of Schwann Cells, Schwann cells:, i. Provide myelination (insulation) around the, nerve fibers in PNS, ii. Play important role in nerve regeneration (Chapter 137), iii. Remove cellular debris during regeneration by, their phagocytic activity., SATELLITE CELLS, Satellite cells are the glial cells present on the exterior, surface of PNS neurons., Functions of Satellite Cells, , Functions of Microglia, Satellite cells:, Microglia:, i. Engulf and destroy the microorganisms and, cellular debris by means of phagocytosis, , i. Provide physical support to the PNS neurons, ii. Help in regulation of chemical environment of, ECF around the PNS neurons.
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Chapter, , Receptors, , 139, , DEFINITION, CLASSIFICATION, , , , EXTEROCEPTORS, INTEROCEPTORS, , PROPERTIES, , , , , , , , SPECIFICITY OF RESPONSE, ADAPTATION – SENSORY ADAPTATION, RESPONSE TO INCREASE IN THE STRENGTH OF STIMULUS, SENSORY TRANSDUCTION, RECEPTOR POTENTIAL, LAW OF PROJECTION, , DEFINITION, Receptors are sensory (afferent) nerve endings that, terminate in periphery as bare unmyelinated endings, or in the form of specialized capsulated structures., Receptors give response to the stimulus. When stimu, lated, receptors produce a series of impulses, which, are transmitted through the afferent nerves., Biological Transducers, Actually receptors function like a transducer. Trans, ducer is a device, which converts one form of energy, into another. So, receptors are often defined as the, biological transducers, which convert (transducer), various forms of energy (stimuli) in the environment into, action potentials in nerve fiber., , Exteroceptors are divided into three groups:, 1. Cutaneous Receptors or Mechanoreceptors, Receptors situated in the skin are called the cutaneous, receptors. Cutaneous receptors are also called mech, anoreceptors because of their response to mechanical, stimuli such as touch, pressure and pain. Touch and, pressure receptors give response to vibration also., Different types of cutaneous receptors are given in, Figure 139.1., 2. Chemoreceptors, Receptors, which give response to chemical stimuli,, are called the chemoreceptors., , CLASSIFICATION OF RECEPTORS, , 3. Telereceptors, , Generally, receptors are classified into two types:, A. Exteroceptors, B. Interoceptors., , Telereceptors are the receptors that give response to, stimuli arising away from the body. These receptors are, also called the distance receptors (Fig. 139.2)., , EXTEROCEPTORS, , INTEROCEPTORS, , Exteroceptors are the receptors, which give response, to stimuli arising from outside the body., , Interoceptors are the receptors, which give response, to stimuli arising from within the body.
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776 Section 10 t Nervous System, Interoceptors are of two types which are as follows:, 1. Visceroceptors, Receptors situated in the viscera are called visce, roceptors. Different visceroceptors are listed in Figure, 139.3., 2. Proprioceptors, Proprioceptors are the receptors, which give response, to change in the position of different parts of the body., Proprioceptors are explained in Chapter 156., , PROPERTIES OF RECEPTORS, 1. SPECIFICITY OF RESPONSE –, MÜLLER LAW, , FIGURE 139.1: Cutaneous receptors, , Specificity of response or Müller law refers to the, response given by a particular type of receptor to a, specific sensation. For example, pain receptors give, response only to pain sensation. Similarly, temperature, receptors give response only to temperature sensation., In addition, each type of sensation depends upon the, part of the brain in which its fibers terminate., Specificity of response is also called Müller’s doc, trine of specific nerve energies., , FIGURE 139.2: Exteroceptors
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Chapter 139 t Receptors 777, , FIGURE 139.3: Interoceptors, , 2. ADAPTATION – SENSORY ADAPTATION, , 4. SENSORY TRANSDUCTION, , Adaptation is the decline in discharge of sensory, impulses when a receptor is stimulated continuously, with constant strength. It is also called sensory, adaptation or desensitization., Depending upon adaptation time, receptors are, divided into two types:, i. Phasic receptors, which get adapted rapidly., Touch and pressure receptors are the phasic, receptors, ii. Tonic receptors, which adapt slowly. Muscle, spindle, pain receptors and cold receptors are, the tonic receptors., , Sensory transduction in a receptor is a process by, which the energy (stimulus) in the environment is, converted into electrical impulses (action potentials) in, nerve fiber (transduction = conversion of one form of, energy into another)., When a receptor is stimulated, it gives response, by sending information about the stimulus to CNS., Series of events occur to carry out this function such, as the development of receptor potential in the receptor, cell and development of action potential in the sensory, nerve., Sensory transduction varies depending upon the, type of receptor. For example, the chemoreceptor con, verts chemical energy into action potential in the sensory, nerve fiber. Touch receptor converts mechanical energy, into action potential in the sensory nerve fiber., , 3. RESPONSE TO INCREASE IN STRENGTH, OF STIMULUS – WEBERFECHNER LAW, During the stimulation of a receptor, if the response given, by the receptor is to be doubled, the strength of stimulus, must be increased 100 times. This phenomenon is, called WeberFechner law, which states that intensity of, response (sensation) of a receptor is directly proportional, to logarithmic increase in the intensity of stimulus., Derivation of Weber-Fechner Law, WeberFechner law is derived as follows:, R = k log S, Where,, R = Intensity of response (sensation), k = Constant, S = Intensity of stimulus, , 5. RECEPTOR POTENTIAL, Definition, Receptor potential is a nonpropagated transmem, brane potential difference that develops when a receptor, is stimulated. It is also called generator potential., Receptor potential is short lived and hence, it is called, transient receptor potential., , Receptor potential is not action potential. It is a, graded potential (Chapter 31). It is similar to excitat, ory postsynaptic potential (EPSP) in synapse, endplate, potential in neuromuscular junction and electrotonic, potential in the nerve fiber.
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778 Section 10 t Nervous System, extends through the corpuscle as center core fiber., The concentric layers of the corpuscle surround the, core fiber of the nerve., Pacinian corpuscles give response to pressure, stimulus. When pressure stimulus is applied, the Paci, nian corpuscle is compressed. This compression, causes elongation or change in shape of the corpuscle., The change in shape of the corpuscle leads to the, deformation of center core fiber of the corpuscle. This, results in the opening of mechanically gated sodium, channels (Chapter 3). So, the positively charged sodium, , FIGURE 139.4: Receptor potential in pacinian corpuscle., Receptor potential leads to development of local circuit, which spreads up to first node within the capsule. It leads to, development of action potential in the first node of nerve fiber., , Properties of Receptor Potential, Receptor potential has two important properties., i. Receptor potential is nonpropagated; it is con, fined within the receptor itself, ii. It does not obey allornone law., Significance of Receptor Potential, When receptor potential is sufficiently strong (when the, magnitude is about 10 mV), it causes development of, action potential in the sensory nerve., Mechanism of Development of Receptor Potential, Pacinian corpuscles are generally used to study the, receptor potential because of their large size and, anatomical configuration. These corpuscles can be, easily dissected from the mesentery of experimental, animals. In the pacinian corpuscle, the tip of the nerve, fiber is unmyelinated. This unmyelinated nerve tip, , FIGURE 139.5: Schematic diagram showing development of, receptor potential and generation of action potential in nerve, fiber.
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Chapter 139 t Receptors 779, ions enter the interior of core fiber. This produces a mild, depolarization, i.e. receptor potential (Fig. 139.4)., , site stimulated. This phenomenon is known as law of, projection., , Generation of Action Potential in the Nerve Fiber, , Examples of Law of Projection, , Receptor potential causes development of a local circuit, of current flow, which spreads along the unmyelinated, part of nerve fiber within the corpuscle., When this local circuit of current reaches the first, node of Ranvier within the corpuscle, it causes open, ing of voltagegated sodium channels and entrance, of sodium ions into the nerve fiber. This leads to, the development of action potential in the nerve fiber, (Fig. 139.5)., 6. LAW OF PROJECTION, When a sensory pathway from receptor to cerebral, cortex is stimulated on any particular site along its, course, the sensation caused by stimulus is always, felt (referred) at the location of receptor, irrespective of, , i. If somesthetic area in right cerebral cortex,, which receives sensation from left hand is, stimulated, sensations are felt in left hand and not, in head., ii. Sensation complained by amputated patients in, the missing limb (phantom limb) is the best example, of law of projection. For example, if a leg has been, amputated, the cut end heals with scar formation., The cut ends of nerve fibers are merged within, the scar. If the cut end of sensory fibers are, stimulated during movement of thigh, the patient, feels as if the sensation is originating from non, existent leg. Sometimes, the patient feels pain, in nonexistent limb. This type of pain is called, phantom limb pain.
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Chapter, , Synapse, , 140, , DEFINITION, CLASSIFICATION, , , , ANATOMICAL CLASSIFICATION, FUNCTIONAL CLASSIFICATION, , FUNCTIONAL ANATOMY, FUNCTIONS, , , , EXCITATORY FUNCTION, INHIBITORY FUNCTION, , PROPERTIES, , , , , , , ONE WAY CONDUCTION – BELL-MAGENDIE LAW, SYNAPTIC DELAY, FATIGUE, SUMMATION, ELECTRICAL PROPERTY, , CONVERGENCE AND DIVERGENCE, , , , CONVERGENCE, DIVERGENCE, , DEFINITION, Synapse is the junction between two neurons. It, is not an anatomical continuation. But, it is only a, physiological continuity between two nerve cells., , 2. Axodendritic synapse in which the axon of one, neuron terminates on dendrite of another neuron, 3. Axosomatic synapse in which axon of one neuron, ends on soma (cell body) of another neuron, (Fig. 140.1)., , CLASSIFICATION OF SYNAPSE, , FUNCTIONAL CLASSIFICATION, , Synapse is classified by two methods:, A. Anatomical classification, B. Functional classification., , Functional classification of synapse is on the basis, of mode of impulse transmission. According to this,, synapse is classified into two categories:, 1. Electrical synapse, 2. Chemical synapse., However, generally the word synapse refers to a, chemical synapse., , ANATOMICAL CLASSIFICATION, Usually synapse is formed by axon of one neuron, ending on the cell body, dendrite or axon of the next, neuron. Depending upon ending of axon, synapse is, classified into three types:, 1. Axoaxonic synapse in which axon of one neuron, terminates on axon of another neuron, , 1. Electrical Synapse, Electrical synapse is the synapse in which the physiolo, gical continuity between the presynaptic and the post
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Chapter 140 t Synapse 781, 2. Chemical Synapse, Chemical synapse is the junction between a nerve fiber, and a muscle fiber or between two nerve fibers, through, which the signals are transmitted by the release of, chemical transmitter. In the chemical synapse, there is, no continuity between the two neurons because of the, presence of a space called synaptic cleft between the, two neurons. Action potential reaching the presynaptic, terminal causes release of neurotransmitter substance, from the vesicles of this terminal. Neurotransmitter, reaches the postsynaptic neuron through synaptic cleft, and causes the production of potential change. Structure, and functions of the chemical synapse are given here., , FUNCTIONAL ANATOMY, OF CHEMICAL SYNAPSE, FIGURE 140.1: Anatomical synapses, , synaptic neurons is provided by gap junction between, the two neurons (Fig. 140.2). There is direct exchange, of ions between the two neurons through the gap, junction. Because of this reason, the action potential, reaching the terminal portion of presynaptic neuron, directly enters the postsynaptic neuron., Important feature of electrical synapse is that the, synaptic delay is very less because of the direct flow of, current. Moreover, the impulse is transmitted in either, direction through the electrical synapse., This type of impulse transmission occurs in some, tissues like the cardiac muscle fibers, smooth muscle, fibers of intestine and the epithelial cells of lens in the, eye., , FIGURE 140.2: Electrical and chemical synapse, , Functional anatomy of a chemical synapse is shown, in Figure 140.3. Neuron from which the axon arises, is called the presynaptic neuron and the neuron on, which the axon ends is called postsynaptic neuron., Axon of the presynaptic neuron divides into many small, branches before forming the synapse. These branches, are known as presynaptic axon terminals., Types of Axon Terminals, 1. Terminal knobs, Some of the terminals are enlarged slightly like knobs, called terminal knobs. Terminal knobs are concerned, with excitatory function of the synapse., , FIGURE 140.3: Structure of chemical synapse
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782 Section 10 t Nervous System, 2. Terminal coils or free endings, Other terminals are wavy or coiled with free ending, without the knob. These terminals are concerned with, inhibitory function., Structures of Axon Terminals and, Presynaptic Membrane, Presynaptic axon terminal has a definite intact mem, brane known as presynaptic membrane., Axon terminal has two important structures:, i. Mitochondria, which help in the synthesis of, neurotransmitter substance, ii. Synaptic vesicles, which store neurotransmitter, substance., , naptic membrane and synaptic cleft and reaches the, postsynaptic membrane. Now, the neurotransmitter, binds with receptor protein present in postsynaptic, membrane to form neurotransmitterreceptor complex., Neurotransmitterreceptor complex causes production, of a nonpropagated EPSP. Common excitatory, neurotransmitter in a synapse is acetylcholine., Mechanism of Development of EPSP, Neurotransmitterreceptor complex causes opening of, ligandgated sodium channels. Now, the sodium ions, , Synaptic Cleft and Postsynaptic Membrane, Membrane of the postsynaptic neuron is called postsynaptic membrane. It contains some receptor, proteins. Small space in between the presynaptic, , membrane and the postsynaptic membrane is called, synaptic cleft. The basal lamina of this cleft contains, cholinesterase, which destroys acetylcholine., , FUNCTIONS OF SYNAPSE, Main function of the synapse is to transmit the, impulses, i.e. action potential from one neuron to, another. However, some of the synapses inhibit these, impulses. So the impulses are not transmitted to the, postsynaptic neuron., On the basis of functions, synapses are divided into, two types:, 1. Excitatory synapses, which transmit the impulses, (excitatory function), 2. Inhibitory synapses, which inhibit the transmission, of impulses (inhibitory function)., EXCITATORY FUNCTION, Excitatory Postsynaptic Potential, Excitatory postsynaptic potential (EPSP) is the non, propagated electrical potential that develops during, the process of synaptic transmission. When the action, potential reaches the presynaptic axon terminal, the, voltagegated calcium channels at the presynaptic, membrane are opened. Now, the calcium ions enter, the axon terminal from ECF (Fig. 140.4)., Calcium ions cause the release of neurotransmitter, substance from the vesicles by means of exocytosis., Neurotransmitter, which is excitatory in function, (excitatory neurotransmitter) passes through presy, , FIGURE 140.4: Sequence of events during synaptic, transmission. Ach = Acetylcholine, ECF = Extracellular fluid,, EPSP = Excitatory postsynaptic potential.
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Chapter 140 t Synapse 783, from ECF enter the cell body of postsynaptic neuron., As the sodium ions are positively charged, resting, membrane potential inside the cell body is altered, and mild depolarization develops. This type of mild, depolarization is called EPSP. It is a local potential, (response) in the synapse., Properties of EPSP, EPSP is confined only to the synapse. It is a graded, potential (Chapter 31). It is similar to receptor potential, and endplate potential., EPSP has two properties:, 1. It is nonpropagated, 2. It does not obey allornone law., , channels. Now, the potassium ions, which are available, in plenty in the cell body of postsynaptic neuron move to, ECF. Simultaneously, chloride channels also open and, chloride ions (which are more in ECF) move inside the cell, body of postsynaptic neuron. The exit of potassium ions, and influx of chloride ions cause more negativity inside,, leading to hyperpolarization. Hyperpolarized state of the, synapse inhibits synaptic transmission (Fig. 140.5)., 2. Presynaptic or Indirect Inhibition, Presynaptic inhibition occurs due to the failure of, presynaptic axon terminal to release sufficient quantity, of excitatory neurotransmitter substance. It is also called, indirect inhibition., , Significance of EPSP, EPSP is not transmitted into the axon of postsynaptic, neuron. However, it causes development of action, potential in the axon., When EPSP is strong enough, it causes the opening, of voltagegated sodium channels in the initial segment, of axon. Now, due to the entrance of sodium ions, the, depolarization occurs in the initial segment of axon, and thus, the action potential develops. From here, the, action potential spreads to other segment of the axon., INHIBITORY FUNCTION, Inhibition of synaptic transmission is classified into five, types:, 1. Postsynaptic or direct inhibition, 2. Presynaptic or indirect inhibition, 3. Negative feedback or Renshaw cell inhibition, 4. Feedforward inhibition, 5. Reciprocal inhibition., 1. Postsynaptic or Direct Inhibition, Postsynaptic inhibition is the type of synaptic inhibition, that occurs due to the release of an inhibitory neuro, transmitter from presynaptic terminal instead of an, excitatory neurotransmitter substance. It is also called, direct inhibition. Inhibitory neurotransmitters are gamma, aminobutyric acid (GABA), dopamine and glycine., Action of GABA – development of inhibitory, postsynaptic potential, Inhibitory postsynaptic potential (IPSP) is the electrical, potential in the form of hyperpolarization that develops, during postsynaptic inhibition. Inhibitory neurotransmitter, substance acts on postsynaptic membrane by binding, with receptor. Transmitterreceptor complex opens the, ligandgated potassium channels instead of sodium, , FIGURE 140.5: Sequence of events during postsynaptic, inhibition. GABA = Gammaaminobutyric acid, ECF = Extra, cellular fluid, IPSP = Inhibitory postsynaptic potential.
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784 Section 10 t Nervous System, Presynaptic inhibition is mediated by axoaxonal, synapses. It is prominent in spinal cord and regulates the, propagation of information to higher centers in brain., Normally, during synaptic transmission, action poten, tial reaching the presynaptic neuron produces develop, ment of EPSP in the postsynaptic neuron. But, in spinal, cord, a modulatory neuron called presynaptic inhibitory, neuron forms an axoaxonic synapse with the presynaptic, neuron (Fig. 140.6)., This inhibitory neuron inhibits the presynaptic neu, ron and decreases the magnitude of action potential, in presynaptic neuron. The smaller action potential, reduces calcium influx. This in turn decreases the, quantity of neurotransmitter released by presynaptic, neuron. So the magnitude of EPSP in postsynaptic, neuron is decreased resulting in synaptic inhibition., 3. Renshaw Cell or Negative Feedback Inhibition, Negative feedback inhibition is the type of synaptic, inhibition, which is caused by Renshaw cells in spinal, cord. Renshaw cells are small motor neurons present, in anterior gray horn of spinal cord (Chapter 143)., Anterior nerve root consists of nerve fibers, which, leave the spinal cord. These nerve fibers arise from, αmotor neurons in anterior gray horn of the spinal cord, and reach the effector organ, muscles. Some of the, fibers called collaterals fibers terminate on Renshaw, cells instead of leaving the spinal cord., , FIGURE 140.7: Renshaw cell inhibition, , When motor neurons send motor impulses,, some of the impulses reach the Renshaw cell by, passing through collaterals. Now, the Renshaw cell, is stimulated. In turn, it sends inhibitory impulses to, αmotor neurons so that, the discharge from motor, neurons is reduced (Fig. 140.7)., In this way, Renshaw cell inhibition represents a, negative feedback mechanism. A Renshaw cell may be, supplied by more than one alpha motor neuron collateral, and it may synapse on many motor neurons., 4. Feedforward Inhibition, Feedforward synaptic inhibition occurs in cerebellum, and it controls the neuronal activity in cerebellum., During the process of neuronal activity in cerebellum,, stellate cells and basket cells, which are activated by, granule cells, inhibit the Purkinje cells by releasing, GABA (Chapter 150). This type of inhibition is called, feedforward inhibition., 5. Reciprocal Inhibition, Inhibition of antagonistic muscles when a group of, muscles are activated is called reciprocal inhibition. It is, because of reciprocal innervation (Chapter 142)., Significance of Synaptic Inhibition, , FIGURE 140.6: Presynaptic inhibition, , Synaptic inhibition in CNS limits the number of impulses, going to muscles and enables the muscles to act, properly and appropriately. Thus, the inhibition helps, to select exact number of impulses and to omit or, block the excess ones. When a poison like strychnine, is introduced into the body, it destroys the inhibitory
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Chapter 140 t Synapse 785, function at synaptic level resulting in continuous and, convulsive contraction even with slight stimulation. In, the nervous disorders like parkinsonism, the inhibitory, system is impaired resulting in rigidity., , PROPERTIES OF SYNAPSE, 1. ONE WAY CONDUCTION –, BELL-MAGENDIE LAW, According to BellMagendie law, the impulses are, transmitted only in one direction in synapse, i.e. from, presynaptic neuron to postsynaptic neuron., 2. SYNAPTIC DELAY, , 4. SUMMATION, Summation is the fusion of effects or progressive in, crease in the excitatory postsynaptic potential in post, synaptic neuron when many presynaptic excitatory, terminals are stimulated simultaneously or when single, presynaptic terminal is stimulated repeatedly. Increased, EPSP triggers the axon potential in the initial segment, of axon of postsynaptic neuron (Fig.140.8)., Summation is of two types:, i. Spatial Summation, Spatial summation occurs when many presynaptic, terminals are stimulated simultaneously., , Synaptic delay is a short delay that occurs during the, transmission of impulses through the synapse. It is due, to the time taken for:, i. Release of neurotransmitter, ii. Passage of neurotransmitter from axon terminal, to postsynaptic membrane, iii. Action of the neurotransmitter to open the ionic, channels in postsynaptic membrane., Normal duration of synaptic delay is 0.3 to 0.5, millisecond. Synaptic delay is one of the causes for, reaction time of reflex activity., Significance of Determining Synaptic Delay, Determination of synaptic delay helps to find out, whether the pathway for a reflex is monosynapatic or, polysynaptic., 3. FATIGUE, During continuous muscular activity, synapse becomes, the seat of fatigue along with Betz cells present in motor, area of frontal lobe of cerebral cortex (Refer Chapter 30, for details of fatigue). Fatigue at synapse is due to the, depletion of neurotransmitter substance, acetylcholine., Depletion of acetylcholine occurs because of two, factors:, i. Soon after the action, acetylcholine is destroyed, by acetylcholinesterase, ii. Due to continuous action, new acetylcholine is, not synthesized., , FIGURE 140.8: Spatial and temporal summation
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786 Section 10 t Nervous System, , FIGURE 140.9: Convergence and divergence, , ii. Temporal Summation, , CONVERGENCE AND DIVERGENCE, , Temporal summation occurs when one presynaptic, terminal is stimulated repeatedly., Thus, both spatial summation and temporal summa, tion play an important role in facilitation of response., , CONVERGENCE, , 5. ELECTRICAL PROPERTY, Electrical properties of the synapse are the EPSP and, IPSP, which are already described in this chapter., , Convergence is the process by which many presynaptic, neurons terminate on a single postsynaptic neuron, (Fig.140.9)., DIVERGENCE, Divergence is the process by which one presynaptic, neuron terminates on many postsynaptic neurons.
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Neurotransmitters, , , , , , , , , , , , Chapter, , 141, , DEFINITION, HISTORY, CRITERIA, CLASSIFICATION, TRANSPORT AND RELEASE, INACTIVATION, REUPTAKE, IMPORTANT NEUROTRANSMITTERS, NEUROMODULATORS, COTRANSMISSION AND COTRANSMITTERS, , DEFINITION, Neurotransmitter is a chemical substance that acts as, a mediator for the transmission of nerve impulse from, one neuron to another neuron through a synapse., , HISTORY, Existence of neurotransmitter was first discovered by, an Austrian scientist named Otto Loewi in 1921. He, dreamt of an experiment, which he did practically and, came out with this discovery., Loewi Experiment, Otto Loewi used two frogs for this experiment. Heart of, frog A was with intact vagus nerve and was placed in a, saline-filled chamber. Heart of frog B was denervated, and was kept in another saline-filled chamber. Both, the chambers were connected in such a way that, the fluid from chamber of frog A could flow into the, chamber of frog B., When vagus nerve of frog A was electrically, stimulated, slowing of heart rate was observed. After, a short delay, the heart rate in frog B also was found, to be slowing down. From this observation, Loewi, speculated that some chemical substance must have, , been released from the vagus nerve of frog A, which, was responsible for the slowing down of the heart rate, in frog B. He named it as ‘vagusstoff’. Later this chemical substance was considered as a neurotransmitter, and called acetylcholine (Ach)., , CRITERIA FOR NEUROTRANSMITTER, Nowadays, many substances are categorized as neurotransmitters. To consider a substance as a neurotransmitter, it should fulfill certain criteria as given, below:, 1. It must be found in a neuron, 2. It must be produced by a neuron, 3. It must be released by a neuron, 4. After release, it must act on a target area and produce some biological effect, 5. After the action, it must be inactivated., , CLASSIFICATION, OF NEUROTRANSMITTERS, DEPENDING UPON CHEMICAL NATURE, Many substances of different chemical nature are, identified as neurotransmitters. Depending upon their
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788 Section 10 t Nervous System, chemical nature, neurotransmitters are classified into, three groups., 1. Amino Acids, Neurotransmitters of this group are involved in fast, synaptic transmission and are inhibitory and excitatory, in action. GABA, glycine, glutamate (glutamic acid) and, aspartate (aspartic acid) belong to this group., , DEPENDING UPON FUNCTION, Some of the neurotransmitters cause excitation of postsynaptic neuron while others cause inhibition., Thus, neurotransmitters are classified into two, types:, 1. Excitatory neurotransmitters, 2. Inhibitory neurotransmitters., , 2. Amines, , 1. Excitatory Neurotransmitters, , Amines are the modified amino acids. These neurotransmitters involve in slow synaptic transmission., These neurotransmitters are also inhibitory and excitatory in action. Noradrenaline, adrenaline, dopamine,, serotonin and histamine belong to this group., , Excitatory neurotransmitter is a chemical substance,, which is responsible for the conduction of impulse, from presynaptic neuron to postsynaptic neuron., Neurotransmitter released from the presynaptic axon, terminal does not cause development of action potential, in the postsynaptic neuron. Rather, it causes some, change in the resting membrane potential, i.e. slight depolarization by the opening of sodium channels in the, postsynaptic membrane and the influx of sodium ions, from ECF. This slight depolarization is called excitatory, postsynaptic potential (EPSP). EPSP in turn causes, development of action potential in the initial segment of, the axon of the postsynaptic neuron (Chapter 140)., , 3. Others, Some neurotransmitters do not fit into any of these, categories. One such substance is acetylcholine. It is, formed from the choline and acetyl coenzyme A in the, presence of the enzyme called choline acetyltransferase., Another substance included in this category is the, soluble gas nitric oxide (NO)., , TABLE 141.1: Neurotransmitters, , Others, , Amines, , Aminoacids, , Group, , Name, , Site of secretion, , Action, , GABA, , Cerebral cortex, cerebellum, basal ganglia, retina and spinal cord, , Inhibitory, , Glycine, , Forebrain, brainstem, spinal cord and retina, , Inhibitory, , Glutamate, , Cerebral cortex, brainstem and cerebellum, , Excitatory, , Aspartate, , Cerebellum, spinal cord and retina, , Excitatory, , Noradrenaline, , Postganglionic adrenergic sympathetic nerve endings, cerebral cortex,, hypothalamus, basal ganglia, brainstem, locus coeruleus and spinal cord, , Excitatory and, inhibitory, , Adrenaline, , Hypothalamus, thalamus and spinal cord, , Excitatory and, inhibitory, , Dopamine, , Basal ganglia, hypothalamus, limbic system, neocortex, retina and, sympathetic ganglia, , Inhibitory, , Serotonin, , Hypothalamus, limbic system, cerebellum, spinal cord, retina,, gastrointestinal (GI) tract, lungs and platelets, , Inhibitory, , Histamine, , Hypothalamus, cerebral cortex, GI tract and mast cells, , Excitatory, , Nitric oxide, , Many parts of CNS, neuromuscular junction and GI tract, , Excitatory, , Acetylcholine, , Preganglionic parasympathetic nerve endings, Postganglionic parasympathetic nerve endings, Preganglionic sympathetic nerve endings, Postganglionic sympathetic cholinergic nerve endings, Neuromuscular junction, cerebral cortex, hypothalamus, basal ganglia,, thalamus, hippocampus and amacrine cells of retina, , Excitatory, , GABA = Gamma-aminobutyric acid, CNS = Central nervous system.
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Chapter 141 t Neurotransmitters 789, Common excitatory neurotransmitters are acetyl, choline and noradrenaline., , 2. Inhibitory Neurotransmitters, Inhibitory neurotransmitter is a chemical substance, which, inhibits the conduction of impulse from the presynaptic, neuron to the postsynaptic neuron (Chapter 140). When, it is released from the presynaptic axon terminal due, to the arrival of action potential, it causes opening of, potassium channels in the postsynaptic membrane and, efflux of potassium ions. This leads to hyperpolarization,, which is called the inhibitory postsynaptic potential, (IPSP). When IPSP is developed, the action potential is, not generated in the postsynaptic neuron., Common inhibitory neurotransmitters are gamma, aminobutyric acid (GABA) and dopamine., , TRANSPORT AND RELEASE, OF NEUROTRANSMITTER, , REUPTAKE OF NEUROTRANSMITTER, Reuptake is a process by which the neurotransmitter, is taken back from synaptic cleft into the axon terminal, after execution of its action. Reuptake process involves, a specific carrier protein for each neurotransmitter., , IMPORTANT NEUROTRANSMITTERS, Some of the important neurotransmitters are described, here. Details of neurotransmitters are given in Tables, 141.1 and 141.2., ACETYLCHOLINE, Acetylcholine is a cholinergic neurotransmitter., It possesses excitatory function. It produces the, excitatory function by opening the ligand-gated sodium, channels (Chapters 32 and 140)., Source, , Neurotransmitter is produced in the cell body of the, neuron and is transported through axon. At the axon, terminal, the neurotransmitter is stored in small packets, called vesicles. Under the influence of a stimulus,, these vesicles open and release the neurotransmitter, into synaptic cleft. It binds to specific receptors on, the surface of the postsynaptic cell. Receptors are G, proteins, protein kinase or ligand-gated receptors., , INACTIVATION OF NEUROTRANSMITTER, After the execution of the action, neurotransmitter is, inactivated by four different mechanisms:, 1. It diffuses out of synaptic cleft to the area where it, has no action, 2. It is destroyed or disintegrated by specific enzymes, 3. It is engulfed and removed by astrocytes (macrophages), 4. It is removed by means of reuptake into the axon, terminal., , Acetylcholine is the transmitter substance at the neuromuscular junction and synapse. It is also released by, the following nerve endings:, 1. Preganglionic parasympathetic nerve, 2. Postganglionic parasympathetic nerve, 3. Preganglionic sympathetic nerve, 4. Postganglionic sympathetic cholinergic nerves:, i. Nerves supplying eccrine sweat glands, ii. Sympathetic vasodilator nerves in skeletal, muscle, 5. Nerves in amacrine cells of retina, 6. Many regions of brain., Synthesis, Ach is synthesized in the cholinergic nerve endings., Synthesis takes place in axoplasm and Ach is stored in, the vesicles. It is synthesized from acetyl coenzyme A, (acetyl CoA). It combines with choline in the presence of, the enzyme choline acetyltransferase to form Ach., , TABLE 141.2: Excitatory and inhibitory neurotransmitters, Excitatory neurotransmitters, 1. Acetylcholine, 2. Nitric oxide, 3. Histamine, 4. Glutamate, 5. Aspartate, , Inhibitory, neurotransmitters, 1. Gamma-aminobutyric acid, 2. Glycine, 3. Dopamine, 4. Serotonin, , Neurotransmitters with excitatory, and inhibitory actions, 1. Noradrenaline, 2. Adrenaline
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790 Section 10 t Nervous System, Fate, Action of Ach is short lived. Within one millisecond, after the release from the vesicles, it is hydrolyzed, into acetate and choline by the enzyme acetylcholin, esterase (Fig. 141.1). This enzyme is present in basal, lamina of the synaptic cleft., Acetylcholine Receptors, There are two types of receptors through which Ach, acts on the tissues namely, muscarinic receptors and, nicotinic receptors. Reason for the terminology of, these receptors is as follows: Poisonous substance, from toadstools called muscarine, acts on a specific, group of receptors known as muscarinic receptors;, similarly, another substance called nicotine acts on a, specific group of receptors known as nicotinic receptors, but Ach acts on both the receptors., Muscarinic receptors are present in all the, organs innervated by the postganglionic fibers of the, parasympathetic system and by the sympathetic, cholinergic nerves. Nicotinic receptors are present, in the synapses between preganglionic and postganglionic neurons of both sympathetic and parasympathetic systems., Nicotinic receptors are also present in the neuromuscular junction on membrane of skeletal muscle., NORADRENALINE, Noradrenaline is the neurotransmitter in adrenergic, nerve fibers. It is released from the following structures:, 1. Postganglionic sympathetic nerve endings, 2. Cerebral cortex, , FIGURE 141.1: Synthesis and breakdown of acetylcholine, , 3., 4., 5., 6., 7., , Hypothalamus, Basal ganglia, Brainstem, Locus ceruleus in pons, Spinal cord., In many places, noradrenaline is the excitatory, chemical mediator and in very few places, it causes, inhibition. It is believed to be involved in dreams,, arousal and elevation of moods. Refer Chapter 71 for, the synthesis of noradrenaline., DOPAMINE, Dopamine is secreted by nerve endings in the following, areas:, 1. Basal ganglia, 2. Hypothalamus, 3. Limbic system, 4. Neocortex, 5. Retina, 6. Small, intensely fluorescent cells in sympathetic, ganglia., Dopamine possesses inhibitory action. Prolactin, inhibitory hormone secreted by hypothalamus is considered to be dopamine. Refer Chapter 71 for the, synthesis of dopamine., SEROTONIN, Serotonin is otherwise known as 5hydroxytryptamine, (5-HT). It is synthesized from tryptophan by hydroxylation and decarboxylation. Large amount of serotonin, (90%) is found in enterochromatin cells of GI tract., Small amount is found in platelets and nervous system., It is secreted in the following structures:, 1. Hypothalamus, 2. Limbic system, 3. Cerebellum, 4. Dorsal raphe nucleus of midbrain, 5. Spinal cord, 6. Retina, 7. GI tract, 8. Lungs, 9. Platelets., It is an inhibitory substance. It inhibits impulses of, pain sensation in posterior gray horn of spinal cord. It, is supposed to cause depression of mood and sleep, (Chapter 145). Serotonin causes vasoconstriction,, platelet aggregation and smooth muscle contraction. It, also controls food intake.
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Chapter 141 t Neurotransmitters 791, HISTAMINE, , NITRIC OXIDE, , Histamine is secreted in nerve endings of hypothalamus,, limbic cortex and other parts of cerebral cortex. It is also, secreted by gastric mucosa and mast cells. Histamine, is an excitatory neurotransmitter. It is believed to play, an important role in arousal mechanism., , Nitric oxide (NO) is a neurotransmitter in the CNS. It, is also the important neurotransmitter in the neuromuscular junctions between the inhibitory motor fibers, of intrinsic nerve plexus and the smooth muscle fibers, of GI tract., Nitric oxide acts as a mediator for the dilator effect, of Ach on small arteries. In the smooth muscle fibers of, arterioles, NO activates the enzyme guanylyl cyclase,, which in turn causes formation of cyclic guanosine, monophosphate (cGMP) from GMP. The cGMP is a, smooth muscle relaxant and it causes dilatation of arterioles. Thus, NO indirectly causes dilatation of arterioles., Peculiarity of NO is that it is neither produced, by the neuronal cells nor stored in the vesicles. It is, produced by nonneuronal cells like the endothelial, cells of blood vessels. From the site of production,, it diffuses into the neuronal and non-neuronal cells, where it exerts its action., , GAMMAAMINOBUTYRIC ACID, Gamma-aminobutyric acid (GABA) is an inhibitory, neurotransmitter in synapses particularly in CNS. It is, responsible for presynaptic inhibition. It is secreted by, nerve endings in the following structures:, 1. Cerebral cortex, 2. Cerebellum, 3. Basal ganglia, 4. Spinal cord, 5. Retina., GABA causes synaptic inhibition by opening potassium channels and chloride channels. So, potassium, comes out of synapse and chloride enters in (Chapter, 140). This leads to hyperpolarization, which is known as, inhibitory postsynaptic potential (IPSP)., , NEUROMODULATORS, Definition, , SUBSTANCE P, Substance P is a neuropeptide that acts as a neurotransmitter and as a neuromodulator (see below)., Substance P is a polypeptide with 11 amino acid, residues. It belongs to a family of 3 related peptides, called neurokinins or tachykinins. The other peptides, of this family are neurokinin A and neurokinin B which, are not well known like substance P., Substance P is secreted by the nerve endings, (first order neurons) of pain pathway in spinal cord. It, is also found in many peripheral nerves, different parts, of brain particularly hypothalamus, retina and intestine, (Chapter 44)., It mediates pain sensation. It is a potent vasodilator, in CNS. It is responsible for regulation of anxiety, stress,, mood disorders, neurotoxicity, nausea and vomiting., , Neuromodulator is the chemical messenger, which, modifies and regulates activities that take place during, the synaptic transmission., These peptides do not propagate nerve impulses, like neurotransmitters., Neuromodulators Vs Neurotransmitters, Neuromodulators are distinct from neurotransmitters., However, both the terms are wrongly interchanged., Neurotransmitters propagate nerve impulses through, synapse whereas neuromodulators modify and regulate, the activities of synaptic transmission (Table 141.3)., Neurotransmitters are packed in small vesicles in, axon terminals only. But neuromodulators are generally, , TABLE 141.3: Differences between neurotransmitters and neuromodulators, Sl No, , Neurotransmitters, , Neuromodulators, , 1, , Propagate nerve impulse through synapse, , Modify and regulate synaptic transmission, , 2, , Packed in small synaptic vesicles, , Packed in large synaptic vesicles, , 3, , Found only in axon terminals, , Found in all parts of the body, , 4, , Generally, neuron has only one neurotransmitter, , Neuron may have one or more neuromodulators, , 5, , Act by changing the electric potential – depolarization or, repolarization, , Have diverse actions, , 6, , Chemically, neurotransmitters are amino acids, amine or others Chemically, neuromodulators are only peptides
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792 Section 10 t Nervous System, packed in large synaptic vesicles, which are present, in all parts of neuron like soma, dendrite, axon and, nerve endings. Many neurons have one conventional, neurotransmitter and one or more neuromodulators., Few peptides like substance P (see above) act as, neurotransmitters and neuromodulators., Actions of Neuromodulators, Neurotransmitters affect the excitability of other, neurons or other tissues (like muscle fiber) by, producing depolarization or hyperpolarization through, the receptors of ionic channels. But neuromodulators, have diverse actions such as:, 1. Regulation of synthesis, breakdown or reuptake of, neurotransmitter, 2. Excitation or inhibition of membrane receptors by acting independently or together with neurotransmitter, 3. Control of gene expression, 4. Regulation of local blood flow, 5. Promotion of synaptic formation, 6. Control of glial cell morphology, 7. Regulation of behavior., Chemistry of Neuromodulators, Generally the neuromodulators are peptides. So neuromodulators are often referred as neuropeptides., Almost all the peptides found in nervous tissues are, neuromodulators., Types of Neuromodulators, Neuromodulators are classified into two types:, 1. Non-opioid peptides, 2. Opioid peptides., NONOPIOID PEPTIDES, Non-opioid neuropeptides act by binding with Gprotein coupled receptors. These neuropeptides are, also called nonopioid neuromodulators. Non-opioid, peptides are listed in Table 141.4., OPIOID PEPTIDES, Peptides, which bind to opioid receptors are called, opioid peptides (Table 141.5). Opioid peptides are also, , called opioid neuropeptides or opioid neuromodulators., Opioid receptors are the membrane proteins located in, nerve endings in brain and GI tract. Opioid receptors, are of three types µ, к and δ. These proteins are called, , opioid receptors because of their affinity towards the, , opiate or morphine, which are derived from opium., Opium is the juice of white poppy (Papaver somni, ferum). It is used as a narcotic to produce hallucinations, and induce sleep. Opiate also induces sleep. Morphine, is a powerful analgesic (pain reliever). Both opiate and, morphine have high medicinal values, but are highly, addictive., These two substances act by binding with the, receptor proteins (opioid receptors) for the natural, neuropeptides. Natural neuropeptides are called, endogenous opioid peptides., , Endogenous opioid peptides have opiate like activity and inhibit the neurons in the brain involved in pain, sensation., Opioid peptides are of three types:, i. Enkephalins, ii. Dynorphins, iii. Endorphins., i. Enkephalins, Enkephalins are the natural opiate peptides recognized, first in pig’s brain. Derived from the precursor proenkephalin, these peptides are present in the nerve endings, in many parts of forebrain, substantia gelatinosa, of brainstem, spinal cord and GI tract. Two types of, enkephalins are known, leucine enkephalin (YGGFL), and methionine enkephalin (YGGFM)., ii. Dynorphins, Dynorphins are derived from prodynorphin. Dynorphins are, found in hypothalamus, posterior pituitary and duodenum., Dynorphins are of two types, α- and β-dynorphins., iii. Endorphins, Endorphins are the large peptides derived from the, precursor pro-opiomelanocortin. Endorphins are predominant in diencephalic region particularly hypothalamus and anterior and intermediate lobes of pituitary, gland. Three types of endorphins are recognized, α-, βand γ-endorphins., , COTRANSMISSION, AND COTRANSMITTERS, Cotransmission is the release of many neurotransmitters, from a single nerve terminal. Cotransmitters are the
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Chapter 141 t Neurotransmitters 793, TABLE 141.4: Nonopioid neuromodulators, Name, , Site of secretion, , Action, , Bradykinin, , Blood vessels, kidneys, , Vasodilator, , Substance P, , Brain, spinal cord, retina peripheral nerves and intestine, , Mediates pain. Regulates anxiety, stress,, mood disorders, neurotoxicity, nausea and, vomiting. Causes vasodilatation., , Secretin, , Cerebral cortex, hypothalamus, thalamus, olfactory bulb,, brainstem and small intestine, , Inhibits gastric secretion and motility, , CCK, , Cerebral cortex, hypothalamus, retina and small intestine, , Contracts gallbladder, Inhibits gastric motility, Increases intestinal motility, , Gastrin, , Hypothalamus, medulla oblongata, posterior pituitary and, gastrointestinal (GI) tract, , Increases gastric secretion and motility, Stimulates islets in pancreas, , VIP, , Cerebral cortex, hypothalamus, retina and intestine, , Causes vasodilatation, , Motilin, , Cerebral cortex, cerebellum, posterior pituitary and, intestine, , Stimulates intestinal motility, , Neurotensin, , Hypothalamus and retina, , Inhibits pain sensation, Decreases food intake, , Vasopressin, , Posterior pituitary, medulla oblongata and spinal cord, , Causes vasoconstriction, , Oxytocin, , Posterior pituitary, medulla oblongata and spinal cord, , Stimulates milk ejection and uterine, contraction, , CRH, , Hypothalamus, , Stimulates release of ACTH, , GHRH, , Hypothalamus, , Stimulates release of growth hormone, , GHRP, , Hypothalamus, , Stimulates release of GHRH, , TRH, , Hypothalamus, other parts of brain and retina, , Stimulates release of thyroid hormones, , Somatostatin, , Hypothalamus, other parts of brain, substantia gelatinosa, and retina, , Inhibits growth hormone secretion, Decreases food intake, , GnRH, , Hypothalamus, preganglionic autonomic nerve endings, and retina, , Inhibits gonadotropin secretion, , Endothelin, , Posterior pituitary, brainstem and endothelium, , Causes vasoconstriction, , Angiotensin II, , Hypothalamus, brainstem and spinal cord, , Causes vasoconstriction, , ANP, , Hypothalamus, brainstem and heart, , Causes vasodilatation, Increases sodium excretion, , BNP, , Hypothalamus and heart, , Causes vasodilatation, Increases sodium excretion, , CNP, , Brain, myocardium, endothelium of blood vessels, GI, tract and kidneys, , Causes vasodilatation, Increases sodium excretion, , Neuropeptide Y, , Medulla, hypothalamus and small intestine, , Increases food intake, Causes vasoconstriction, Increases enteric blood flow, , Ghrelin, , Hypothalamus, stomach, pituitary, kidney and placenta, , Promotes GH release, Induces appetite and food intake, Stimulates gastric emptying, , ACTH = Adrenocorticotropic hormone, ANP = Atrial natriuretic peptide, BNP = Brain natriuretic peptide, CCK = Cholecystokinin., CNP = C-type natriuretic peptide, CRH = Corticotropin-releasing hormone, GHRH = Growth hormone-releasing hormone,, GHRP = Growth hormone-releasing polypeptide, GnRH = Gonadotropin-releasing hormone, TRH = Thyrotropin-releasing, hormone, VIP = Vasoactive intestinal polypeptide.
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794 Section 10 t Nervous System, TABLE 141.5: Opioid neuromodulators, Name, , Site of secretion, , Enkephalins, , Many parts of brain, substantia gelatinosa and retina, , Dynorphins, , Hypothalamus, posterior pituitary and duodenum, , β-endorphin, , Thalamus, hypothalamus, brainstem and retina, , neurotransmitter substances that are released in, addition to primary transmitter at the nerve endings., For many years, it was believed that each neuron, releases only one neurotransmitter substance from its, terminals. Now it is known that some of the neurons, release many neurotransmitter substances. It is also, believed that the additional neurotransmitters, i.e. the, cotransmitters modulate the effects of primary neurotransmitters., Some of the primary neurotransmitters act as cotransmitters in other nerve endings., , Action, Inhibit pain sensation, , Examples of cotransmitters:, 1., 2., 3., 4., 5., 6., 7., 8., 9., 10., , Calcitonin, Dopamine, Dynorphin, GABA, Gene-related peptide, Glutamate, Glycine, Neuropeptide Y, Substance P, Vasoactive intestinal polypeptide (VIP).
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Chapter, , Reflex Activity, , , , , , , , , , , , 142, , DEFINITION AND SIGNIFICANCE OF REFLEXES, REFLEX ARC, CLASSIFICATION OF REFLEXES, SUPERFICIAL REFLEXES, DEEP REFLEXES, VISCERAL REFLEXES, PATHOLOGICAL REFLEXES, PROPERTIES OF REFLEXES, RECIPROCAL INHIBITION AND RECIPROCAL INNERVATION, REFLEXES IN MOTOR NEURON LESION, , DEFINITION AND SIGNIFICANCE, OF REFLEXES, Reflex activity is the response to a peripheral nervous, stimulation that occurs without our consciousness. It is, a type of protective mechanism and it protects the body, from irreparable damages., For example, when hand is placed on a hot object,, it is withdrawn immediately. When a bright light is, thrown into the eyes, eyelids are closed and pupil is, constricted to prevent the damage of retina by entrance, of excessive light into the eyes., , FIGURE 142.1: Simple reflex arc, , 3. Center, , REFLEX ARC, Reflex arc is the anatomical nervous pathway for a, reflex action. A simple reflex arc includes five components (Fig. 142.1)., , Center receives the sensory impulses via afferent, nerve fibers and in turn, it generates appropriate motor, impulses. Center is located in the brain or spinal cord., 4. Efferent Nerve, , 1. Receptor, Receptor is the end organ, which receives the stimulus., When receptor is stimulated, impulses are generated, in afferent nerve., 2. Afferent Nerve, Afferent or sensory nerve transmits sensory impulses, from the receptor to center., , Efferent or motor nerve transmits motor impulses from, the center to the effector organ., 5. Effector Organ, Effector organ is the structure such as muscle or gland, where the activity occurs in response to stimulus., Afferent and efferent nerve fibers may be connected, directly to the center. In some places, one or more
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796 Section 10 t Nervous System, neurons are interposed between these nerve fibers, and the center. Such neurons are called connector, neurons or internuncial neurons or interneurons., , CLASSIFICATION OF REFLEXES, Reflexes are classified by six different methods depending upon various factors. Different methods of classification are listed in Box 142.1., BOX 142.1: Different methods to classify reflexes, Classification of reflexes, 1. Depending upon whether inborn or acquired, 2. Depending upon situation – anatomical classification, 3. Depending upon purpose – physiological, classification, 4. Depending upon number of synapse, 5. Depending upon whether visceral or somatic, 6. Depending upon clinical basis, , 1. DEPENDING UPON WHETHER INBORN, OR ACQUIRED REFLEXES, i. Inborn Reflexes or Unconditioned Reflexes, Unconditioned reflexes are the natural reflexes, which, are present since the time of birth, hence the name inborn, reflexes. Such reflexes do not require previous learning,, training or conditioning. Best example is the secretion, of saliva when a drop of honey is kept in the mouth of a, newborn baby for the first time. The baby does not know, the taste of honey, but still saliva is secreted., ii. Acquired Reflexes or Conditioned Reflexes, Conditioned or acquired reflexes are the reflexes that, are developed after conditioning or training. These, reflexes are not inborn but, acquired after birth. Such, reflexes need previous learning, training or conditioning., Example is the secretion of saliva by sight, smell, thought, or hearing of a known edible substance., 2. DEPENDING UPON SITUATION –, ANATOMICAL CLASSIFICATION, In this method, reflexes are classified depending upon, the situation of the center., i. Cerebellar Reflexes, Cerebellar reflexes are the reflexes which have their, center in cerebellum., ii. Cortical Reflexes, Cortical reflexes are the reflexes that have their center, in cerebral cortex., , iii. Midbrain Reflexes, Midbrain reflexes are the reflexes which have their, center in midbrain., iv. Bulbar or Medullary Reflexes, Bulbar or medullary reflexes are the reflexes which have, their center in medulla oblongata., v. Spinal Reflexes, Reflexes having their center in the spinal cord are, called spinal reflexes. Depending upon the segments, involved, spinal reflexes are divided into three groups:, a. Segmental spinal reflexes, b. Intrasegmental spinal reflexes, c. Suprasegmental spinal reflexes., 3. DEPENDING UPON PURPOSE –, PHYSIOLOGICAL CLASSIFICATION, In this method, reflexes are classified depending upon, the purpose (functional significance)., i. Protective Reflexes or Flexor Reflexes, Protective reflexes are the reflexes which protect the, body from nociceptic (harmful) stimuli. These reflexes, are also called withdrawal reflexes or flexor reflexes., Protective reflexes involve flexion at different joints, hence the name flexor reflexes., ii. Antigravity Reflexes or Extensor Reflexes, Antigravity reflexes are the reflexes that protect the, body against gravitational force. These reflexes are, also called the extensor reflexes because, the extensor, muscles contract during these reflexes resulting in, extension at joints., 4. DEPENDING UPON THE NUMBER, OF SYNAPSE, Depending upon the number of synapse in reflex arc,, reflexes are classified into two types:, i. Monosynaptic Reflexes, Reflexes having only one synapse in the reflex arc are, called monosynaptic reflexes. Stretch reflex is the best, example for monosynaptic reflex and it is elicited due, to the stimulation of muscle spindle.
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Chapter 142 t Reflex Activity 797, ii. Polysynaptic Reflexes, Reflexes having more than one synapse in the reflex, arc are called polysynaptic reflexes. Flexor reflexes, (withdrawal reflexes) are the polysynaptic reflexes., 5. DEPENDING UPON WHETHER, SOMATIC OR VISCERAL REFLEXES, i. Somatic Reflexes, , iii. Visceral reflexes, iv. Pathological reflexes., , SUPERFICIAL REFLEXES, Superficial reflexes are the reflexes, which are elicited, from the surface of the body. Superficial reflexes are, of two types: mucus membrane reflexes and skin, reflexes., , Somatic reflexes are the reflexes, for which the reflex, arc is formed by somatic nerve fibers. These reflexes, involve the participation of skeletal muscles. And there, may be flexion or extension at different joints during, these reflexes., , 1. MUCOUS MEMBRANE REFLEXES, , ii. Visceral or Autonomic Reflexes, , 2. CUTANEOUS REFLEXES OR, SKIN REFLEXES, , Visceral or autonomic reflexes are the reflexes, for, which at least a part of reflex arc is formed by autonomic, nerve fibers. These reflexes involve participation of, smooth muscle or cardiac muscle. Visceral reflexes, include pupillary reflexes, gastrointestinal reflexes,, cardiovascular reflexes, respiratory reflexes, etc., Some reflexes like swallowing, coughing or, vomiting are considered as visceral reflexes. However,, these reflexes involve some participation of skeletal, muscles also., 6. DEPENDING UPON CLINICAL BASIS, Depending upon the clinical basis, reflexes are classified, into four types:, i. Superficial reflexes, ii. Deep reflexes, , Mucous membrane reflexes arise from the mucus, membrane. Details of mucus membrane reflexes are, listed in Table 142.1., , Cutaneous reflexes are elicited from skin by the, stimulation of cutaneous receptors. Details of these, reflexes are given in Table 142.2., , DEEP REFLEXES, Deep reflexes are elicited from deeper structures, beneath the skin like tendon. These reflexes are, otherwise known as tendon reflexes. Details of these, are given in Table 142.3., , VISCERAL REFLEXES, Visceral reflexes are the reflexes arising from pupil, and visceral organs. Other details of visceral reflexes, are already given above., , TABLE 142.1: Superficial mucous membrane reflexes, Reflex, , Stimulus, , Response, , Afferent Nerve, , Center, , Efferent Nerve, , 1. Corneal reflex, , Irritation of cornea, , Blinking of eye, (closure of, eyelids), , 2. Conjunctival, reflex, , Irritation of, conjunctiva, , Blinking of eye, , V cranial nerve, , Pons, , 3. Nasal reflex, (sneezing reflex), , Irritation of, nasal mucus, membrane, , Sneezing, , V cranial nerve, , Motor nucleus of V X cranial nerve and, cranial nerve, upper cervical, nerves, , 4. Pharyngeal, reflex, , Irritation of, pharyngeal, mucus, membrane, , Retching or, gagging (opening, of mouth), , IX cranial nerve, , Nuclei of X cranial, nerve, , X cranial nerve, , 5. Uvular reflex, , Irritation of uvula, , Raising of uvula, , IX cranial nerve, , Nuclei of X cranial, nerve, , X cranial nerve, , V cranial nerve, , Pons, , VII cranial nerve, VII cranial nerve
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798 Section 10 t Nervous System, TABLE 142.2: Superficial cutaneous reflexes, Reflex, , Stimulus, , Response, , Center – spinal, segments involved, , 1. Scapular reflex, , Irritation of skin at the, interscapular space, , Contraction of scapular muscles and, drawing in of scapula, , C5 to T1, , 2. Upper abdominal, reflex, , Stroking the abdominal wall, below the costal margin, , Ipsilateral contraction of abdominal muscle, and movement of umbilicus towards the, site of stroke, , T6 to T9, , 3. Lower abdominal, reflex, , Stroking the abdominal wall at, umbilical and iliac level, , Ipsilateral contraction of abdominal muscle, and movement of umbilicus towards the, site of stroke, , T10 to T12, , 4. Cremasteric, reflex, , Stroking the skin at upper and, inner aspect of thigh, , Elevation of testicles, , L1, L2, , 5. Gluteal reflex, , Stroking the skin over glutei, , Contraction of glutei, , L4 to S1,2, , 6. Plantar reflex, , Stroking the sole, , Plantar flexion and adduction of toes, , 7. Bulbocavernous, reflex, , Stroking the dorsum of glans, penis, , Contraction of bulbocavernosus, , S3, S4, , 8. Anal reflex, , Stroking the perianal region, , Contraction of anal sphincter, , S4, S5, , L5 to S2, , TABLE 142.3: Deep reflexes, Reflex, , Stimulus, , Response, , Center – spinal, segments involved, , 1. Jaw jerk, , Tapping middle of the chin with, slightly opened mouth, , Closure of mouth, , Pons – V cranial, nerve, , 2. Biceps jerk, , Percussion of biceps tendon, , Flexion of forearm, , C5, C6, , 3. Triceps jerk, , Percussion of triceps tendon, , Extension of forearm, , 4. Supinator jerk or radial, periosteal reflex, , Percussion of tendon over, distal end (styloid process) of, radius, , Supination and flexion of forearm, , C7, C8, , 5. Wrist tendon or finger, flexion reflex, , Percussion of wrist tendons, , Flexion of corresponding finger, , C8, T1, , 6. Knee jerk or patellar tendon, reflex, , Percussion of patellar ligament, , Extension of leg, , L2 to L4, , 7. Ankle jerk or Achilles, tendon reflex, , Percussion of Achilles tendon, , Plantar flexion of foot, , L5 to S2, , Following are the visceral reflexes:, 1. Pupillary reflexes, 2. Oculocardiac reflex, 3. Carotid sinus reflex., PUPILLARY REFLEXES, Pupillary reflexes are the reflexes in which, the size of, pupil is altered., Pupillary reflexes are:, i. Light reflex, , C6 to C8, , ii. Accommodation reflex, iii. Ciliospinal reflex., i. Light Reflex, When retina of the eye is stimulated by a sudden flash of, light, constriction of pupil occurs. It is called light reflex., Light reflex of two types:, a. Direct light reflex, in which stimulation of retina, in one eye by flash of light causes constriction, of pupil in the same eye
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Chapter 142 t Reflex Activity 799, b. Indirect or consensual light reflex, in which, stimulation of retina in one eye by flash of light, causes simultaneous constriction of pupil in, the other eye also., , Babinski sign is present in upper motor neuron, lesion. Physiological conditions when Babinski sign, , is present are infancy and deep sleep. It is present in, infants because of non-myelination of pyramidal tracts., , ii. Accommodation Reflex, , CLONUS, , While eyes are fixed on a distant object and if another, object is brought in front of the eye (near the eye) the, vision shifts form far object to near object. During that, time some changes occur in the eyes., Changes during accommodation reflex are:, a. Constriction of pupil, b. Convergence of eyeball, c. Increase in anterior curvature of lens., , Clonus is a series of rapid and repeated involuntary, jerky movements, which occur while eliciting a deep, reflex. When a deep reflex is elicited in a normal person,, the contractions of a muscle or group of muscles are, smooth and continuous. But clonus occurs when the, deep reflexes are exaggerated due to hypertonicity of, muscles in pyramidal tract lesion. Clonus is well seen, in calf muscles producing ankle clonus and quadriceps, producing patella clonus., , iii. Ciliospinal Reflex, Ciliospinal reflex is the dilatation of pupil due to, stimulation of skin over the neck., More details of pupillary reflexes are given in, Chapter 169., OCULOCARDIAC REFLEX, Oculocardiac reflex is the reflex, in which heart rate, decreases due to the pressure applied over eyeball., CAROTID SINUS REFLEX, Carotid sinus reflex is the decrease in heart rate and, blood pressure caused by pressure over carotid sinus, in neck due to tight collar., , PATHOLOGICAL REFLEXES, Pathological reflexes are the reflexes that are elicited, only in pathological conditions. Well-known pathological, reflexes are:, 1. Babinski sign, 2. Clonus, 3. Pendular movements., BABINSKI SIGN, Abnormal plantar reflex is called Babinski sign. It is, , also called Babinski reflex or phenomenon. It is named, after the discoverer Joseph Babinski. In normal plantar, reflex, a gentle scratch over the outer edge of the sole, of foot causes plantar flexion and adduction of all toes., But in Babinski sign, there is dorsiflexion of great toe, and fanning of other toes., When Babinski reflex is present, the condition is, commonly called Babinski positive sign and when it is, negative, the condition is called Babinski negative sign., , Ankle Clonus, Ankle clonus is the repeated rhythmical contractions of, calf muscles caused by sudden dorsiflexion of foot., Repeated rhythmical contractions of calf muscles, lead to a series of rhythmic plantar flexion at ankle, joint. Sudden dorsiflexion of foot is done by supporting, patient’s knee in a slightly flexed position., Patellar Clonus, Patellar clonus is the rhythmic jerky movements of, patella produced by grasping it between thumb and, index finger of the examiner and pushing it down forcibly, towards the foot. It is caused by clonic contractions of, quadriceps muscle., PENDULAR MOVEMENTS, Pendular movements are the slow oscillatory, movements (instead of brisk movements) that are, developed while eliciting a tendon jerk. Unlike clonus,, pendular movements occur because of hypotonicity of, muscles. Pendular movements are very common while, eliciting the knee jerk or patellar tendon reflex in the, patients affected by cerebellar lesion., A tap on the patellar tendon when leg is hanging, freely causes a brisk extension of leg due to the, contraction of quadriceps muscle (knee jerk). In normal, conditions, after the extension, the leg returns back, to resting position immediately. In cerebellar lesion,, the leg swings forwards and backwards several times, before coming to rest. Such movements are similar, to movements of clock’s pendulum hence the name, pendular movements.
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800 Section 10 t Nervous System, , PROPERTIES OF REFLEXES, 1. ONE WAY CONDUCTION, (BELL-MAGENDIE LAW), During any reflex activity, impulses are transmitted in, only one direction through the reflex arc as per BellMagendie law. The impulses pass from receptors to, center and then from center to effector organ., 2. REACTION TIME, Reaction time is the time interval between application, of stimulus and the onset of reflex. It depends upon the, length of afferent and efferent nerve fibers, velocity of, impulse through these fibers and central delay. Central, delay is the delay at the synapse. It is also called, synaptic delay., , 3. SUMMATION, Refer Chapter 140 for details of summation. Summation, in reflex action is of two types:, i. Spatial Summation, When two afferent nerve fibers supplying a muscle are, stimulated separately with subliminal stimulus, there, is no response. But the muscle contracts when both, the nerve fibers are stimulated together with same, strength of stimulus. It is called spatial summation., , But, when both A and B are stimulated together,, the tension produced is (A + B) = 12 units. Thus, the, tension here is less than sum of tension produced when, A and B were stimulated separately. This phenomenon, is called occlusion. Occlusion is due to the overlapping, of the nerve fibers during the distribution., 5. SUBLIMINAL FRINGE, In some reflexes involving the muscle with two nerve, fibers, the tension developed by simultaneous stimulation of two nerves is greater than the sum of tension, produced by the stimulation of these nerves separately., For example, if nerve A is stimulated alone, the, arbitrary unit of tension developed by muscle = 3 units, (Fig. 142.3). If nerve B is stimulated alone, the tension, produced = 3 units. So, the sum of tension developed,, if nerves A and B are stimulated separately = 3 + 3 = 6, units. When both the nerves A and B were stimulated, together, the tension developed is (A + B) = 12 units., Thus, the tension here is greater than the sum of, tension produced, if A and B are separately stimulated., This phenomenon is called subliminal fringe. It is due to, the effect of spatial summation., 6. RECRUITMENT, Recruitment is defined as the successive activation of, additional motor units with progressive increase in force, of muscular contraction., , ii. Temporal Summation, When one nerve fiber is stimulated repeatedly with, subliminal stimuli, these stimuli are summed up to, give response in the muscle. It is called temporal, summation., Thus, both spatial summation and temporal summation play an important role in the facilitation of res, ponses during the reflex activity., 4. OCCLUSION, Occlusion is demonstrated in a flexor reflex involving, a muscle, which is innervated by two motor nerves., These nerves can be called A and B. When both the, nerves, A and B, are stimulated simultaneously, the, tension developed by the muscle is less than the sum, of the tension developed when each nerve is stimulated, separately., For example, if nerve A is stimulated alone, the, arbitrary unit of tension developed is 9. If the nerve B is, stimulated then 9 units of tension is developed. So, the, sum of tension developed when the nerves A and B are, separately stimulated = 9 + 9 = 18 units (Fig. 142.2)., , FIGURE 142.2: Occlusion, , FIGURE 142.3: Subliminal fringe
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Chapter 142 t Reflex Activity 801, When an excitatory nerve is stimulated for a long, time, there is a gradual increase in the response of, reflex activities. It is due to the activation of more and, more motor neurons. Recruitment is similar to the, effect of temporal summation., Indefinite increase in response does not produce, unlimited recruitment. A plateau is reached. Thus,, there is a limit to the number of motor neurons, which, are recruited. So, beyond certain limit, the prolongation, of stimulation does not increase the response., 7. AFTER DISCHARGE, After discharge is the persistence or continuation, of response for some time even after cessation of, stimulus. When a reflex action is elicited continuously, for sometime and then the stimulation is stopped, the, reflex activity (contraction) will be continued for sometime even after the stoppage of the stimulus. It is, because of the discharge of impulses from the center, even after stoppage of stimulus. Internuncial neurons,, which continue to transmit afferent impulses even, after stoppage of stimulus are responsible for after, discharge., 8. REBOUND PHENOMENON, Reflex activities can be forcefully inhibited for some, time. But, when the inhibition is suddenly removed,, the reflex activity becomes more forceful than before, inhibition. It is called rebound phenomenon. Reason, for this state of over excitation is not known., , Reciprocal inhibition occurs because of the reciprocal innervation., RECIPROCAL INNERVATION –, SHERRINGTON LAW, Neural mechanism involved in reciprocal inhibition, was postulated by Sherrington. Hence, it is called, Sherrington law of reciprocal innervation. According to, this law, the reciprocal inhibition is due to segmental, arrangement of afferent and efferent connections in the, spinal cord. Afferent nerve fibers, which evoke flexor, reflex in a limb, have connections with motor neurons, supplying flexors and the motor neurons supplying, the extensors of same side. Afferent nerve excites the, motor neurons, which supply the flexors., Simultaneously, it also inhibits the motor neurons, supplying extensors through an interneuron. Accordingly, the flexor muscles contract and extensor muscles, relax resulting in flexion of the limb (Fig. 142.4)., CROSSED EXTENSOR REFLEX, Crossed extensor reflex is the withdrawal reflex in, which the flexors of the withdrawing limb are excited, (contracting) and extensors are inhibited (relaxed),, while the opposite occurs in the other limb. For example,, while eliciting a flexor reflex activity in a limb, that limb is, flexed. Simultaneously the opposite limb is extended., , 9. FATIGUE, When a reflex activity is continuously elicited for a long, time, the response is reduced slowly and at one stage,, the response does not occur. This type of failure to give, response to the stimulus is called fatigue. Center or the, synapse of the reflex arc is the first seat of fatigue., , RECIPROCAL INHIBITION AND, RECIPROCAL INNERVATION, RECIPROCAL INHIBITION, Reciprocal inhibition is one of the important features of, both flexor and extensor reflexes. Usually, excitation, of one group of muscles is associated with inhibition, of another, i.e. antagonistic group of muscles on the, same side. For example, when a flexor reflex is elicited,, the flexor muscles are excited (contracted) and the, extensor muscles are inhibited (relaxed) in that side., This phenomenon is called the reciprocal inhibition., , FIGURE 142.4: Reciprocal inhibition, (+) = Excitation. (–) = Inhibition.
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802 Section 10 t Nervous System, Crossed extensor reflex is demonstrated in a spinal, animal. When one limb of the animal is pinched, it is, withdrawn, i.e. flexed. But the opposite limb is extended, (Fig. 142.5)., SIGNIFICANCE OF RECIPROCAL INHIBITION, Reciprocal inhibition and reciprocal innervation are, very important in spinal reflexes, which are involved in, locomotion. It helps in the forward movement of one, limb while causing the backward movement of the, opposite limb., , REFLEXES IN MOTOR NEURON LESION, UPPER MOTOR NEURON LESION, FIGURE 142.5: Crossed extensor reflex. Green lines indicate, excitation and red lines indicate inhibition., , Flexors are excited and extensors are inhibited in this, limb, but in the opposite limb, the flexors are inhibited, and extensors are excited. This type of crossed extensor, reflex is because of reciprocal inhibition. It occurs in, upper motor neuron lesion., , During upper motor neuron lesion, all the superficial, reflexes are lost. Deep reflexes are exaggerated and, the Babinski sign is positive (Chapter 144)., LOWER MOTOR NEURON LESION, During lower motor lesion, all the superficial and deep, reflexes are lost (Chapter 144).
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Chapter, , Spinal Cord, , , , , , , , , 143, , INTRODUCTION, GRAY MATTER, WHITE MATTER, TRACTS IN SPINAL CORD, ASCENDING TRACTS, DESCENDING TRACTS, APPLIED PHYSIOLOGY, , INTRODUCTION, , medullaris. A slender non-nervous filament called filum, terminale extends from conus medullaris downward to, , Situation and Extent, , the fundus of the dural sac at the level of second sacral, vertebra., , Spinal cord lies loosely in the vertebral canal. It, extends from foramen magnum where it is continuous, with medulla oblongata, above and up to the lower, border of first lumbar vertebra below., Coverings, Spinal cord is covered by sheaths called meninges,, which are membranous in nature. Meninges are dura, mater, pia mater and arachnoid mater. These coverings, continue as coverings of brain. Meninges are responsible, for protection and nourishment of the nervous tissues., Shape and Length, Spinal cord is cylindrical in shape. Length of the spinal cord, is about 45 cm in males and about 43 cm in females., Enlargements, Spinal cord has two spindle-shaped swellings, namely, cervical and lumbar enlargements. These two portions, , of spinal cord innervate upper and lower extremities, respectively., , Segments, Spinal cord is made up of 31 segments, which are, listed in Box 143.1. In fact, spinal cord is a continuous, structure. Appearance of the segment is by nerves, arising from spinal cord, which are called spinal nerve., Spinal Nerves, Segments of spinal cord correspond to 31 pairs of, spinal nerves in a symmetrical manner. The spinal, nerves are listed in Box 143.1., BOX 143.1: Segments of spinal cord and spinal nerves, Spinal segments/Spinal nerves, 1., 2., 3., 4., 5., , Cervical segments/Cervical spinal nerves, Thoracic segments/Thoracic spinal nerves, Lumbar segments/Lumbar spinal nerves, Sacral segments/Sacral spinal nerves, Coccygeal segment/Coccygeal spinal nerves, , = 8, = 12, = 5, = 5, = 1, , Total, , = 31, , Conus Medullaris and Filum Terminale, , Nerve Roots, , Below the lumbar enlargement, spinal cord rapidly, narrows to a cone-shaped termination called conus, , Each spinal nerve is formed by an anterior (ventral), root and a posterior (dorsal) root. Both the roots on
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804 Section 10 t Nervous System, either side leave the spinal cord and pass through, the corresponding intervertebral foramina. The, first cervical spinal nerves pass through a foramen, between occipital bone and first vertebra, which is, called atlas. Cervical and thoracic roots are shorter, whereas, the lumbar and sacral roots are longer. Long, nerves descend in dural sac to reach their respective, intervertebral foramina. This bundle of descending, roots surrounding the filum terminale resembles the, tail of horse. Hence, it is called cauda equina., Fissure and Sulci, On the anterior surface of spinal cord, there is a deep, furrow known as anterior median fissure. Depth of this, fissure is about 3 mm. Lateral to the anterior median, fissure on either side, there is a slight depression, called the anterolateral sulcus. It denotes the exit of, anterior nerve root. On the posterior aspect, there is, a depression called posterior median sulcus. This, sulcus is continuous with a thin glial partition called the, posterior median septum. It extends inside the spinal, cord for about 5 mm and reaches the gray matter., On either side, lateral to posterior median sulcus,, there is posterior intermediate sulcus. It is continuous, with posterior intermediate septum, which extends for, about 3 mm into the spinal cord. Lateral to the posterior, intermediate sulcus, is the posterolateral sulcus. This, denotes the entry of posterior nerve root., , Internal Structure of Spinal Cord, Neural substance of spinal cord is divided into inner, gray matter and outer white matter (Fig. 143.1)., , GRAY MATTER OF SPINAL CORD, Gray matter of spinal cord is the collection of nerve, cell bodies, dendrites and parts of axons. It is placed, centrally in the form of wings of the butterfly and it, resembles the letter ‘H’. Exactly in the center of gray, matter, there is a canal called the spinal canal., Ventral and the dorsal portions of each lateral half, of gray matter are called ventral (anterior) and dorsal, (posterior) gray horns respectively. In addition, the gray, matter forms a small projection in between the anterior, and posterior horns in all thoracic and first two lumbar, segments. It is called the lateral gray horn. Part of the, gray matter anterior to central canal is called the anterior, gray commissure and part of gray matter posterior to, the central canal is called posterior gray commissure., Neurons in Gray Matter of Spinal Cord, Gray matter contains two types of multipolar neurons:, 1. Golgi type I neurons, Golgi type I neurons have long axons and are usually, found in anterior horns. Axons of these neurons form, the long tracts of spinal cord., , FIGURE 143.1: Section of spinal cord: thoracic segment
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Chapter 143 t Spinal Cord 805, Golgi type II neurons, Golgi type II neurons have short axons, which are found, mostly in posterior horns. Axons of these neurons pass, towards the anterior horn of same side or opposite side., Organization of Neurons in Gray Matter, Organization of neurons in the gray matter of spinal cord, is described in two methods:, 1. Nuclei or columns, 2. Laminae or layers (Fig. 143.2)., NUCLEI, Clusters of neurons are present in the form of nuclei or cell, columns in gray matter. Advantage of this method is that, different nuclei are easily distinguished. Disadvantage, is that some neurons like internuncial neurons, which, are outside the distinct nuclei are not included., , covers the very tip of posterior gray horn and it is found, in all levels of spinal cord., 2. Substantia gelatinosa of Rolando, Substantia gelatinosa of Rolando is a cap-like gelatinous, material at the apex of posterior horn situated in all levels, of spinal cord. It is formed by small neurons., 3. Chief sensory nucleus or nucleus proprius, Chief sensory nucleus is situated in the posterior gray, horn ventral to substantia gelatinosa. It is a poorly, defined cell column located in all segments of spinal cord., 4. Dorsal nucleus of Clarke, Clarke nucleus is also called Clarke column of cells and, it is the collection of well-defined neurons. It occupies, the basal portion of posterior horn. This nucleus is found, in spinal segments between C8 and L3 only., , Nuclei in Posterior Gray Horn, Posterior gray horn contains the nuclei of sensory neurons, which receive impulses from various receptors, of the body through posterior nerve root fibers. There, are four types of nuclei of sensory neurons:, 1. Marginal nucleus, Marginal nucleus is also called posteromarginal, nucleus, marginal zone nucleus or border nucleus. It, , Nuclei in Lateral Gray Horn, Lateral gray horn has cluster of neurons called intermediolateral nucleus. The neurons of this nucleus, give rise to sympathetic preganglionic fibers, which, leave the spinal cord through the anterior nerve root., Intermediolateral nucleus extends between T1 and L2, segments of spinal cord., , FIGURE 143.2: Neurons in gray horn of spinal cord: thoracic segment
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806 Section 10 t Nervous System, Nuclei in Anterior Gray Horn, , Laminae in Anterior Gray Horn, , Anterior gray horn contains the nuclei of lower motor, neurons, which are involved in motor function. These, nuclei are present in almost all the levels of spinal cord., Three types of motor neurons are present in lower, motor neuron nuclei:, , Laminae VIII and IX form the anterior gray horn. These, laminae contain nuclei of motor neurons, which are, concerned with motor functions., , 1. Alpha motor neurons, Alpha motor neurons are large and multipolar cells., Axons of these neurons leave the spinal cord through, the anterior root and end in groups of skeletal muscle, fibers called extrafusal fibers., 2. Gamma motor neurons, Gamma motor neurons are smaller cells scattered, among alpha motor neurons. These neurons send, axons to intrafusal fibers of the muscle spindle., 3. Renshaw cells, These cells are also smaller in size. Renshaw cells are, the inhibitory neurons, which play an important role in, synaptic inhibition at the spinal cord (Chapter 140)., LAMINAE, Neurons of gray matter are distributed in laminae or, layers. Each lamina consists of neurons of different, size and shape. This cytoarchitectural lamination, was identified in 1950 by Brian Burke and Rexed., He classified the neurons in 10 laminae based on his, observation on sections of brain in a neonatal cat., Laminae are also called Rexed laminae., Advantage of this method is that all the neurons, of gray horn are included. Disadvantage is that it is, difficult to distinguish the laminae from one another., , Neurons present in the laminae of anterior gray horn, Motor internuncial neurons,, : Lamina VIII, which are also called interneurons, Motor neurons, : Lamina IX, Lamina Around Central Canal, There is only one lamina around the center of the, spinal canal, the lamina X. It contains neuroglia, which, form the supporting tissue., , WHITE MATTER OF SPINAL CORD, White matter of spinal cord surrounds the gray matter., It is formed by the bundles of both myelinated and nonmyelinated fibers, but predominantly the myelinated, fibers. Anterior median fissure and posterior median, septum divide the entire mass of white matter into two, lateral halves. The band of white matter lying in front, of anterior gray commissure is called anterior white, commissure (Fig. 143.2)., Each half of the white matter is divided by the, fibers of anterior and posterior nerve roots into three, white columns or funiculi:, I. Anterior or Ventral White Column, Ventral white column lies between the anterior median, fissure on one side and anterior nerve root and anterior, gray horn on the other side. It is also called anterior or, ventral funiculus., , Laminae in Posterior Gray Horn, , II. Lateral White Column, , Laminae I to VI constitute the posterior gray horn. These, laminae contain nuclei of sensory neurons, which are, concerned with sensory functions., , Lateral white column is present between the anterior, nerve root and anterior gray horn on one side and, posterior nerve root and posterior gray horn on the other, side. It is also called lateral funiculus., , Nuclei present in the laminae of posterior gray horn, Marginal nucleus, Substantial gelatinosa, of Rolando, Chief sensory nucleus, Dorsal nucleus of Clarke, , : Lamina I, : Laminae II and III, : Laminae III, IV and V, : Lamina VI, , III. Posterior or Dorsal White Column, Dorsal white column is situated between the posterior, nerve root and posterior gray horn on one side and, posterior median septum on the other side. It is also, called posterior or dorsal funiculus., , Lamina in Lateral Gray Horn, , TRACTS IN SPINAL CORD, , Lateral gray horn contains only one lamina, the lamina, VII. It contains intermediolateral nucleus., , Groups of nerve fibers passing through spinal cord are, known as tracts of the spinal cord. The spinal tracts are
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Chapter 143 t Spinal Cord 807, divided into two main groups. They are:, 1. Short tracts, 2. Long tracts., 1. Short Tracts, Fibers of the short tracts connect different parts of, spinal cord itself., Short tracts are of two types:, i. Association or intrinsic tracts, which connect adjacent segments of spinal cord on the same side, ii. Commissural tracts, which connect opposite halves, of same segment of spinal cord., 2. Long Tracts, Long tracts of spinal cord, which are also called, projection tracts, connect the spinal cord with other, parts of central nervous system., Long tracts are of two types:, i. Ascending tracts, which carry sensory impulses, from the spinal cord to brain, ii. Descending tracts, which carry motor impulses from, brain to the spinal cord., , ASCENDING TRACTS OF SPINAL CORD, Ascending tracts of spinal cord carry the impulses of, various sensations to the brain., Pathway for each sensation is formed by two or, three groups of neurons, which are:, 1. First order neurons, 2. Second order neurons, 3. Third order neurons., First Order Neurons, First order neurons receive sensory impulses from the, receptors and send them to sensory neurons present, in the posterior gray horn of spinal cord through their, fibers. Nerve cell bodies of these neurons are located in, the posterior nerve root ganglion., , Third Order Neurons, Third order neurons are in the subcortical areas. Fibers, of these neurons carry the sensory impulses from, subcortical areas to cerebral cortex., Ascending tracts situated in different white funiculi, are listed in Table 143.1 and their features are given in, Table 143.2., 1. ANTERIOR SPINOTHALAMIC TRACT, Anterior spinothalamic tract is formed by the fibers of, second order neurons of the pathway for crude touch, sensation (Figs. 143.3 and 143.4)., Situation, Anterior spinothalamic tract is situated in anterior, white funiculus near the periphery., Origin, Fibers of anterior spinothalamic tract arise from the, neurons of chief sensory nucleus of posterior gray, horn, which form the second order neurons of the crude, touch pathway. First order neurons are situated in the, posterior nerve root ganglia. These neurons receive the, impulses of crude touch sensation from the pressure, receptors. Axons of the first order neurons reach the, chief sensory nucleus through the posterior nerve root., Course, Anterior spinothalamic tract contains crossed fibers., After taking origin, these fibers cross obliquely in the, anterior white commissure and enter the anterior, white column of opposite side. Here, the fibers ascend, through other segments of spinal cord and brainstem, (medulla, pons and midbrain) and reach thalamus., TABLE 143.1: List of ascending tracts of spinal cord, White column, , 1. Anterior spinothalamic tract, , Lateral white column, , 1. Lateral spinothalamic tract, 2. Ventral spinocerebellar tract, 3. Dorsal spinocerebellar tract, 4. Spinotectal tract, 5. Fasiculus dorsolateralis, 6. Spinoreticular tract, 7. Spino-olivary tract, 8. Spinovestibular tract, , Posterior white, column, , 1. Fasciculus gracilis, 2. Fasciculus cuneatus, 3. Comma tract of Schultze, , Second Order Neurons, Second order neurons are the sensory neurons, present in the posterior gray horn. Fibers from these, neurons form the ascending tracts of spinal cord., These fibers carry sensory impulses from spinal, cord to different brain areas below cerebral cortex, (subcortical areas) such as thalamus., All the ascending tracts are formed by fibers of, second order neurons of the sensory pathways except, the ascending tracts in the posterior white funiculus,, which are formed by the fibers of first order neurons., , Tract, , Anterior white column
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Posterior white, column, , Lateral white column, , Anterior white, column, , Situation, , Nucleus cuneatus in, medulla, , Uncrossed fibers, No synapse in spinal, cord, , Posterior nerve root, ganglia, , 1. Fasciculus gracilis, , 2. Fasciculus cuneatus, , 8. Spinovestibular tract, , Nucleus gracilis in, medulla, , Non-specific, , 7. Spino-olivary tract, , Reticular formation of, brainstem, , Crossed and, uncrossed fibers, , Uncrossed fibers, No synapse in spinal, cord, , Intermediolateral cells, , 6. Spinoreticular tract, , Substantia gelatinosa, , Component of lateral, spinothalamic tract, , Superior colliculus, , Posterior nerve root, ganglia, , Posterior nerve root, ganglion, , 5. Fasiculus, dorsolateralis, , Crossing in spinal cord, , Anterior lobe of, cerebellum, , Lateral vestibular, nucleus, , Chief sensory nucleus, , 4. Spinotectal tract, , Uncrossed fibers, , Anterior lobe of, cerebellum, , Crossed and, uncrossed fibers, , Clarke nucleus, , 3. Dorsal, spinocerebellar tract, , Crossing in spinal cord, , Ventral posterolateral, nucleus of thalamus, , Crossing in spinal cord, Forms spinal lemniscus, , Non-specific, , Marginal nucleus, , 2. Ventral, spinocerebellar tract, , Ventral posterolateral, nucleus of thalamus, , Crossing in spinal cord, Forms spinal lemniscus, , Olivary nucleus, , Substantia gelatinosa, , 1. Lateral spinothalamic, tract, , Termination, , Course, , Uncrossed fibers, , Chief sensory nucleus, , Origin, , 1. Anterior, spinothalamic tract, , Tract, , TABLE 143.2: Ascending tracts of spinal cord, , Tactile sensation, Tactile localization, Tactile discrimination, Vibratory sensation, Conscious kinesthetic, sensation, Stereognosis, , Proprioception, , Proprioception, , Consciousness and, awareness, , Pain and temperature, sensations, , Spinovisual reflex, , Subconscious kinesthetic, sensations, , Subconscious kinesthetic, sensations, , Pain and temperature, sensations, , Crude touch sensation, , Function, , 808 Section 10 t Nervous System
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Chapter 143 t Spinal Cord 809, , FIGURE 143.3: Tracts of spinal cord, , Few fibers of this tract ascend in posterior gray horn, for 2 or 3 segments in the same side and then cross, over to the anterior white column of opposite side., While ascending through brainstem, the number of, fibers is considerably reduced since some of the fibers, form the collaterals and reach the reticular formation of, brainstem., Termination, , 2. LATERAL SPINOTHALAMIC TRACT, Lateral spinothalamic tract is formed by the fibers from, second order neurons of the pathway for the sensations, of pain and temperature (Fig. 143.4)., Situation, Lateral spinothalamic tract is situated in the lateral, column towards medial side, i.e. near the gray matter., , Fibers of anterior spinothalamic tract terminate in the, ventral posterolateral nucleus of thalamus. Neurons, of this thalamic nucleus form third order neurons of the, pathway. Fibers from thalamic nucleus carry the impulses, to somesthetic area (sensory cortex) of cerebral cortex., , Origin, , Function, , Course, , Anterior spinothalamic tract carries impulses of crude, touch (protopathic) sensation., , Lateral spinothalamic tract has crossed fibers. Axons, from marginal nucleus and substantia gelatinosa of, Rolando cross to the opposite side and reach the lateral, column of same segment. Few fibers may ascend one, or two segments, then cross to the opposite side and, then ascend in the lateral column., All the fibers pass through medulla, pons and midbrain and reach thalamus along with fibers of anterior, spinothalamic tract. Some of the fibers of lateral spinothalamic tract form collaterals and reach the reticular, formation of brainstem., , Effect of Lesion, Bilateral lesion of this tract leads to loss of crude, touch sensation and loss of sensations like itching, and tickling. Unilateral lesion of this tract causes loss, of crude touch sensation in opposite side below the, level of lesion (because fibers of this tract cross to the, opposite side in spinal cord)., , Fibers of lateral spinothalamic tract take origin from two, sources:, i. Marginal nucleus, ii. Substantia gelatinosa of Rolando.
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810 Section 10 t Nervous System, anterior spinothalamic tract fibers. From here, third, order neuron fibers run to somesthetic area (sensory, cortex) of cerebral cortex., Function, Fibers of lateral spinothalamic tract carry impulses of, pain and temperature sensations. Fibers arising from, this marginal nucleus transmit impulses of fast pain, sensation. Fibers arising from substantia gelatinosa of, Rolando transmit impulses of slow pain and temperature, sensations. Refer Chapter 145 for details of pain fibers., Effect of Lesion, Bilateral lesion of this tract leads to total loss of pain and, temperature sensations on both sides below the level, of lesion. Unilateral lesion or sectioning of the lateral, spinothalamic tract causes loss of pain (analgesia), and temperature (thermoanesthesia) below the level, of lesion in the opposite side., 3. VENTRAL SPINOCEREBELLAR TRACT, Ventral spinocerebellar tract is also known as Gower, tract, indirect spinocerebellar tract or anterior spino, cerebellar tract. It is constituted by the fibers of second, order neurons of the pathway for subconscious, kinesthetic sensation (Fig. 143.5)., Situation, This tract is situated in lateral white column of the, spinal cord along the lateral periphery., Origin, , FIGURE 143.4: Spinothalamic tracts and pathways for crude, touch, pain and temperature sensations. Anterior spinothalamic, tract (red) carries crude touch sensation. Lateral spinothalamic, tract (blue) carries pain and temperature sensations., , Fibers of this tract arise from the marginal nucleus, in posterior gray horn. Neurons of marginal nucleus, form the second order neurons. Fibers from these, neurons make their first appearance in lower lumbar, segments of spinal cord., First order neurons are in the posterior root, ganglia and receive the impulses of proprioception, from the proprioceptors in muscle, tendon and joints., Fibers from neurons of posterior root ganglia reach, the marginal cells through posterior nerve root., Course, , Fibers of lateral spinothalamic tract form spinal, lemniscus along with the fibers of anterior spinothalamic, tract at the lower part of medulla., Termination, Fibers of lateral spinothalamic tract terminate in the, ventral posterolateral nucleus of thalamus along with, , Ventral spinocerebellar tract contains both crossed, and uncrossed fibers. Majority of the fibers from the, marginal nucleus cross the midline and ascend in, lateral white column of opposite side. Some fibers, ascend in the lateral white column of the same side, also. These nerve fibers ascend through other spinal, segments, medulla, pons and midbrain.
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Chapter 143 t Spinal Cord 811, 4. DORSAL SPINOCEREBELLAR TRACT, Dorsal spinocerebellar tract is otherwise called Flech, sig tract, direct spinocerebellar tract or posterior, spinocerebellar tract. Like the ventral spinocerebellar, tract, this tract is also constituted by the second, order neuron fibers of the pathway for subconscious, kinesthetic sensation. The first order neurons are in, the posterior nerve root ganglia. But, the fibers of this, tract are uncrossed (Fig. 143.5)., Situation, Dorsal spinocerebellar tract is situated in the lateral, column along the posterolateral periphery of spinal, cord. It is situated posterior to ventral cerebellar tract, and anterior to the entry of posterior nerve root., Origin, Fibers of this tract originate from the dorsal nucleus, of Clarke situated in the posterior gray matter of the, spinal cord. First appearance of the fibers is in upper, lumbar segments. From lower lumbar and sacral, segments, the impulses are carried upwards by dorsal, nerve roots to upper lumbar segments., Course, Flechsig tract is formed by uncrossed fibers. Axons, from neurons in dorsal nucleus of Clarke (second order, neurons) reach lateral column of same side. Then,, these fibers ascend through other spinal segments and, reach medulla oblongata. From here, the fibers reach, cerebellum through inferior cerebellar peduncle., FIGURE 143.5: Spinocerebellar tracts and pathway for, subconscious kinesthetic sensation, , Termination, , Finally, the fibers reach the cerebellum through the, superior cerebellar peduncle., , Fibers of this tract end in the cortex of anterior lobe, of cerebellum along with ventral spinocerebellar tract, fibers., , Termination, , Function, , These fibers terminate in the cortex of anterior lobe of, , Along with ventral spinocerebellar tract, the dorsal, spinocerebellar tract carries the impulses of subconscious kinesthetic sensation, which are known as, , cerebellum., , Function, Ventral spinocerebellar tract carries the impulses of, subconscious kinesthetic sensation (proprioceptive, impulses from muscles, tendons and joints). Impulses, of subconscious kinesthetic sensation are also called, non-sensory impulses., , non-sensory impulses., , Effect of Lesion, Unilateral loss of the subconscious kinesthetic, sensation occurs in lesion of this tract on the same, side, as this tract has uncrossed fibers., 5. SPINOTECTAL TRACT, , Effect of Lesion, Lesion of this tract leads to loss of subconscious, kinesthetic sensation in the opposite side., , Spinotectal tract is considered as a component of, anterior spinothalamic tract. It is constituted by the, fibers of second order neurons.
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812 Section 10 t Nervous System, Situation, , Function, , Spinotectal tract occupies the lateral side of lateral, white column, anterior to lateral spinothalamic tract. It, , Fibers of the dorsolateral fasciculus carry impulses of, pain and thermal sensations., , is bound anteriorly by anterior nerve root., Origin, , Fibers of this tract originate from the chief sensory, nucleus (like anterior spinothalamic tract). First appearance of the fibers is in upper lumbar segments. This, tract is very prominent in the cervical segments., Course, Spinotectal tract contains crossed fibers. After taking, origin, the fibers cross to opposite side through anterior, white commissure to the lateral column. Then, these, fibers ascend to the midbrain along with anterior, spinothalamic tract., Termination, Fibers of spinotectal tract end in the superior colliculus, of tectum in midbrain., Function, Spinotectal tract is concerned with spinovisual reflex., 6. FASCICULUS DORSOLATERALIS, Fasciculus dorsolateralis is otherwise called tract of, Lissauer. It is considered as a component of lateral, spinothalamic tract. And, it is constituted by the fibers of, first order neurons., Situation, Lissauer tract is situated in the lateral white column, between the periphery of spinal cord and tip of posterior, gray horn., Origin, , 7. SPINORETICULAR TRACT, Spinoreticular tract is formed by the fibers of second, order neurons., Situation, Spinoreticular tract is situated in anterolateral white, column., Origin, Fibers of this tract arise from intermediolateral nucleus., Course, Spinoreticular tract consists of crossed and uncrossed, fibers. After taking origin, some of the fibers cross the, midline and then ascend upwards. Remaining fibers, ascend up in the same side without crossing., Termination, All the fibers terminate in the reticular formation of, brainstem by three ways:, i. Some fibers terminate in nucleus reticularis, gigantocellularis and lateral reticular nucleus of, medulla in the same side. Some fibers terminate, in the nuclei present in the opposite side., ii. Some fibers terminate in nucleus reticularis, pontis caudalis of the pons in the same side or, opposite side, iii. Very few fibers terminate in midbrain., Function, Fibers of the spinoreticular tract are the components, of ascending reticular activating system and are, concerned with consciousness and awareness., , Lissauer tract is formed by fibers arising from the cells, of posterior root ganglia and enters the spinal cord, , 8. SPINOOLIVARY TRACT, , Course, , Spino-olivary tract is situated in anterolateral part of white, column. Origin of the fibers of this tract is not specific., However, the fibers terminate in olivary nucleus of, medulla oblongata. From here, the neurons project into, cerebellum. This tract is concerned with proprioception., , through lateral division of posterior nerve root., , Lissauer tract contains uncrossed fibers. After, entering spinal cord, the fibers pass upwards or, downwards for few segments on the same side, and synapse with cells of substantia gelatinosa, of Rolando. Axons from these cells (second order, neurons) join the lateral spinothalamic tract., , 9. SPINOVESTIBULAR TRACT, Spinovestibular tract is situated in the lateral white, column of the spinal cord. Fibers of this tract arise from
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Chapter 143 t Spinal Cord 813, all the segments of spinal cord and terminate on the, lateral vestibular nucleus. This tract is also concerned, with proprioception., , 10. FASCICULUS GRACILIS, (TRACT OF GOLL) AND, 11. FASCICULUS CUNEATUS, (TRACT OF BURDACH), Fasciculus gracilis and fasciculus cuneatus are together, called ascending posterior column tracts. These tracts, are formed by the fibers from posterior root ganglia., Thus, both the tracts are constituted by the fibers of, first order neurons of sensory pathway (Fig. 143.6)., Situation, Tracts of Goll and Burdach are situated in posterior, white column of spinal cord hence the name posterior, column tracts. In the cervical and upper thoracic, segments of spinal cord, the posterior white column is, divided by posterior intermediate septum into medial, fasciculus gracilis and lateral fasciculus cuneatus., Thus, the fasciculus gracilis is situated medially in, between posterior median sulcus and posterior median, septum on one side and posterior intermediate sulcus, and posterior intermediate septum on the other side., Fasciculus cuneatus is situated laterally. It is bound, medially by posterior intermediate septum and sulcus, and laterally by posterior gray horn, tract of Lissauer, and posterior nerve root., Origin, Fibers of these two tracts are the axons of first order, neurons. Cell body of these neurons is in the posterior, root ganglia and their fibers form the medial division, (bundle) of posterior nerve root., , FIGURE 143.6: Ascending tracts in posterior white column of, spinal cord and pathway for – 1. Fine touch sensation, 2. Tactile, localization, 3. Tactile discrimination, 4. Vibratory sensation,, 5. Conscious kinesthetic sensation, 6. Stereognosis., , Termination, Course, After entering spinal cord, the fibers ascend through, the posterior white column. These fibers do not, synapse in the spinal cord. Some fibers of medial, division of posterior nerve root descend through, posterior white column in the form of fasciculus, interfascicularis or comma tract of Schultze., Fasciculus gracilis contains the fibers from lower, extremities and lower parts of the body, i.e. from, sacral, lumbar and lower thoracic ganglia of posterior, nerve root. Fasciculus cuneatus contains fibers from, upper part of the body, i.e. from upper thoracic and, cervical ganglia of posterior nerve root., , Tracts of Goll and Burdach terminate in the medulla, oblongata. Fibers of fasciculus gracilis terminate in the, nucleus gracilis and the fibers of fasciculus cuneatus, terminate in the nucleus cuneatus. Neurons of these, medullary nuclei form the second order neurons., Axons of second order neurons form the internal, arcuate fibers. Internal arcuate fibers from both sides, cross the midline forming sensory decussation and, then ascend through pons and midbrain as medial, lemniscus. Fibers of medial lemniscus terminate in, ventral posterolateral nucleus of thalamus. From, here, fibers of the third order neurons relay to sensory, area of cerebral cortex.
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814 Section 10 t Nervous System, Functions, Tracts of the posterior white column convey impulses, of following sensations:, i. Fine (epicritic) tactile sensation, ii. Tactile localization (ability to locate the area of, skin where the tactile stimulus is applied with, closed eyes), iii. Tactile discrimination or two point discrimination, (ability to recognize the two stimuli applied over, the skin simultaneously with closed eyes), iv. Sensation of vibration (ability to perceive the, vibrations from a vibrating tuning fork placed, over bony prominence conducted to deep, tissues through skin). It is the synthetic sense, (Chapter 144) produced by combination of, touch and pressure sensations., v. Conscious kinesthetic sensation (sensation or, awareness of various muscular activities in, different parts of the body), vi. Stereognosis (ability to recognize the known, objects by touch with closed eyes). It is also, a synthetic sense produced by combination of, touch and pressure sensations., Effect of Lesion, Lesion of nerve fibers in tracts of Goll and Burdach or, lesion in the posterior white column leads to the following, symptoms on the same side below the lesion:, i. Loss of fine tactile sensation; however, crude, touch sensation is normal, ii. Loss of tactile localization, iii. Loss of two point discrimination, iv. Loss of sensation of vibration, v. Astereognosis (inability to recognize known, objects by touch while closing the eyes), vi. Lack of ability to differentiate the weight of different objects, vii. Loss of proprioception (inability to appreciate, the position and movement of different parts of, the body), viii. Sensory ataxia or posterior column ataxia, (condition characterized by uncoordinated,, slow and clumsy voluntary movements because, of the loss of proprioception)., 12. COMMA TRACT OF SCHULTZE, Comma tract of schultze is also called fasciculus, interfascicularis. It is situated in between tracts of Goll, and Burdach. This tract is formed by the short descending, , fibers, arising from the medial division of posterior, nerve root. These fibers are also considered as the, descending branches of the tracts of Goll and Burdach., Function of this tract is to establish intersegmental, communications and to form short reflex arc., , DESCENDING TRACTS, OF SPINAL CORD, Descending tracts of the spinal cord are formed by, motor nerve fibers arising from brain and descend into, the spinal cord. These tracts carry motor impulses, from brain to spinal cord., Descending tracts of spinal cord are of two types:, A. Pyramidal tracts, B. Extrapyramidal tracts., Descending tracts are listed in Table 143.3 and, their features given in Table 143.4., PYRAMIDAL TRACTS, Pyramidal tracts were the first tracts to be found in man., Pyramidal tracts of spinal cord are the descending tracts, concerned with voluntary motor activities of the body., These tracts are otherwise known as corticospinal, tracts. There are two corticospinal tracts, the anterior, corticospinal tract and lateral corticospinal tract. While, running from cerebral cortex towards spinal cord, the, fibers of these two tracts give the appearance of a, pyramid on the upper part of anterior surface of medulla, oblongata hence the name pyramidal tracts (Fig. 143.7)., Nerve Fibers, All the fibers of the pyramidal tracts are present, since birth. However, myelination of these fibers is, completed in about 2 years after birth. The pyramidal, tracts on each side have more than a million fibers., About 70% of the fibers are large myelinated fibers, having a diameter of 4 to 22 micron., TABLE 143.3: List of descending tracts of spinal cord, Type, Pyramidal tracts, , Tract, 1. Anterior corticospinal tract, 2. Lateral corticospinal tract, , 1. Medial longitudinal fasciculus, 2. Anterior vestibulospinal tract, 3. Lateral vestibulospinal tract, Extrapyramidal tracts 4. Reticulospinal tract, 5. Tectospinal tract, 6. Rubrospinal tract, 7. Olivospinal tract
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Chapter 143 t Spinal Cord 815, , FIGURE 143.7: Pyramidal tracts, , Large fibers of pyramidal tracts have the tendency, to disappear at old age. Since these tracts are, concerned with control of voluntary movements, the, disappearance of the fibers of pyramidal tracts causes, automatic shivering movements in old age., Fibers of pyramidal tracts are the axons of upper, motor neurons., Origin, Fibers of pyramidal tracts arise from following cells or, areas of cerebral cortex:, 1. Giant cells or Betz cells or pyramidal cells in, precentral gyrus of the motor cortex. These, cells are situated in area 4 (primary motor, area) of frontal lobe., 2. Other areas of motor cortex namely, premotor, area (area 6) and supplementary motor areas, , 3. Other parts of frontal lobe, 4. Somatosensory areas of parietal lobe., It is believed that 30% of pyramidal fibers arise, from primary motor area (area 4) and supplementary, motor areas, another 30% from premotor area, (area 6) and the remaining 40% of fibers arise from, somatosensory areas. All the above fibers form fibers, of upper motor neurons of motor pathway., Course, Corona radiata, After taking origin, the nerve fibers run downwards in, a diffused manner through white matter of cerebral, hemisphere and converge in the form of a fan-like, structure along with ascending fibers, which project, from thalamus to cerebral cortex. This fan-like structure
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Pyramidal, Tracts, , Lateral white, fasciculus, , Anterior white column, , 4. Reticulospinal tract, , 5. Tectospinal tract, , 7. Olivospinal tract, , Lateral white column, , Lateral white column, , Reticular formation of, pons and medulla, , Lateral white column, , 3. Lateral, vestibulospinal tract, , 6. Rubrospinal tract, , Lateral vestibular, nucleus, , Anterior white column, , 2. Anterior, vestibulospinal tract, , Inferior olivary nucleus, , Red nucleus, , Superior colliculus, , Medial vestibular, nucleus, , i. Coordination of voluntary and, reflex movements, ii. Control of muscle tone, iii.Control of respiration and, diameter of blood vessels, Control of movement of head in, response to visual and auditory, impulses, Facilitatory influence on flexor, muscle tone, Control of movements due to, proprioception, , Crossed fibers, Extend up to lower cervical, segments, Crossed fibers, Extend up to thoracic, segments, Mostly crossed, Extent – not clear, , i. Maintenance of muscle tone and, posture, ii. Maintenance of position of head, and body during acceleration, , i. Coordination of reflex ocular, movements, ii. Integration of movements of, eyes and neck, , i. Control of voluntary movements, ii. Form upper motor neurons, , Function, , Mostly uncrossed, Extend up to thoracic, segments, , Mostly uncrossed, Extend to all segments, , Uncrossed fibers, Extend up to upper thoracic, segments, , Uncrossed fibers, Extend up to uppercervical, segments, , Vestibular nucleus, Reticular formation, Superior colliculus and, cells of Cajal, , Anterior white column, , 1. Medial longitudinal, fasciculus, , Crossed fibers, , Lateral white column, , Uncrossed fibers, , Course, , Betz cells and other, cells of motor area, , 2. Lateral corticospinal, tract, , Betz cells and other, cells of motor area, , Origin, , Anterior white column, , Situation, , 1. Anterior corticospinal, tract, , Tract, , Termination – fibers of all the tracts terminate in motor neurons situated in the anterior gray horn of spinal cord., , Extrapyramidal tracts, , TABLE 143.4: Descending tracts of spinal cord, , 816 Section 10 t Nervous System
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Chapter 143 t Spinal Cord 817, is called corona radiata. Thus, corona radiata contains, both ascending fibers from thalamus and descending, fibers from cerebral cortex., Internal capsule, While passing down towards the brainstem the corona, radiata converges in the form of internal capsule. It is, situated in between thalamus and caudate nucleus on, the medial side and lenticular nucleus on the lateral, side (Chapter 148)., In pons, , anterior gray horn either directly or through internuncial, neurons. Pyramidal tract fibers terminate on both, α-motor neurons and β-motor neurons. Axons of the, motor neurons leave the spinal cord as spinal nerves, through anterior nerve roots and supply the skeletal, muscles., Neurons giving origin to the fibers of pyramidal, tract are called the upper motor neurons. Anterior, motor neurons in the spinal cord are called the lower, motor neurons., , Function, , The fibers descend down through internal capsule,, midbrain and pons. While descending through pons,, the fibers are divided into different bundles by the, nuclei of pons. At lower border of pons, the fibers are, grouped once again into a compact bundle and then, descend down into medulla oblongata., , motor impulses from motor area of cerebral cortex to, the anterior motor neurons of the spinal cord. These, two tracts are responsible for fine, skilled movements., , In medulla, , Effects of lesion, , This compact bundle of corticospinal fibers gives the, appearance of a pyramid in the anterior surface of, upper part of medulla. So, the corticospinal tracts are, called the pyramidal tracts., At the lower border of medulla, pyramidal tract, on each side is divided into two bundles of unequal, sizes. About 80% of fibers from each side cross to the, opposite side. While crossing the midline, the fibers of, both sides form the pyramidal decussation., , Lesion in the neurons of motor cortex and the fibers, of pyramidal tracts is called the upper motor neuron, lesion. In human beings, pure pyramidal tract lesions, do not occur. Lesion of pyramidal fibers occurs most, commonly in stroke (cardiovascular accident) due to, hemorrhage and thrombosis. During such lesions, many, extrapyramidal fibers are also damaged along with, pyramidal fibers. Because of this reason, neurologists, often consider the lesion as upper motor neuron lesion, and not as pyramidal tract lesion., Following are the effects of lesion:, , In spinal cord, Fibers which cross the midline and form pyramidal, decussation descend through posterior part of lateral, white column of spinal cord. This bundle of crossed, fibers is called the crossed pyramidal tract or lateral, corticospinal tract or indirect corticospinal tract., Remaining 20% of fibers do not cross to the opposite, side but descend down through the anterior white, column of the spinal cord. This bundle of uncrossed, fibers is called the uncrossed pyramidal tract or, anterior corticospinal tract or direct corticospinal, tract. This tract is well marked in cervical region., Since, the fibers of this tract terminate in different, segments of spinal cord, this tract usually gets thinner, while descending through the successive segments of, spinal cord. Fibers of this tract are absent mostly below, the mid thoracic level. Before termination, majority of, the fibers of this anterior corticospinal tract cross to, the opposite side at different levels of spinal cord., Termination, All the fibers of pyramidal tracts, both crossed and, uncrossed fibers, terminate in the motor neurons of, , Pyramidal tracts are concerned with voluntary movements of the body. Fibers of the pyramidal tracts transmit, , 1. Voluntary movements, Voluntary movements of the body are very much, affected. Initially, there is loss of voluntary movements, in the extremities. Later, it involves the other parts of, the body like hip and shoulder., 2. Muscle tone, Muscle tone is increased leading to spasticity. Muscles, are also paralyzed. This type of paralysis of muscles is, called the spastic paralysis. The spasticity is due to the, failure of inhibitory impulses from upper motor neurons,, particularly the neurons of extrapyramidal system to, reach the γ-motor neurons in spinal cord., However, hypotonia occurs in pure pyramidal tract, lesion, which is very rare. In monkeys, sectioning of, pyramidal tract fibers alone results in hypotonia., 3. Reflexes, All the superficial reflexes are lost and the deep reflexes, are exaggerated. Abnormal plantar reflex called, Babinski sign is present (Babinski sign positive).
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818 Section 10 t Nervous System, More details of upper motor neuron lesion are given, in the next chapter., Effects of Lesion at Different Levels, Cerebral cortex, Lesion of pyramidal tract fibers in cerebral cortex causes, hypertonia, spasticity and contralateral monoplegia, (paralysis of one limb) or contralateral hemiplegia, (paralysis of one side of the body)., Internal capsule, Lesion of pyramidal tract fibers at posterior limb of, internal capsule results in contralateral hemiplegia., Brainstem, Lesion at brainstem involves not only pyramidal tract, fibers but also other structures such as VI and VII, cranial nerve nuclei. So the lesion results in contralateral, hemiparesis (weakness of muscles in one side of the, body) along with VI and VII cranial nerve palsies., Spinal cord, Unilateral lesion of lateral corticospinal fibers at upper, cervical segment causes ipsilateral hemiplegia and, bilateral lesion causes quadriplegia (paralysis of all, four limbs) and paralysis of respiratory muscles., Bilateral lesion of these fibers in thoracic and lumbar, segments results in paraplegia (paralysis of both lower, limbs) without paralysis of respiratory muscles., , Course, After entering the spinal cord from the brainstem, the, fibers of medial longitudinal fasciculus descend through, posterior part of anterior white column of the same side., In the spinal cord, this tract is well defined only in upper, cervical segments. Below this level, the fibers run along, with the fibers of anterior vestibulospinal tract., Extent, Fibers of this tract extend up to the upper cervical, segments of spinal cord., , Termination, Fibers of this tract terminate in anterior motor neurons of, the spinal cord along with fibers of anterior vestibulospinal, tract either directly or through internuncial neurons., Function, Medial longitudinal fasciculus helps in the coordination, of reflex ocular movements and the integration of ocular, and neck movements., Effects of Lesion, Reflex ocular movements and reflex neck movements, are affected in the lesion of this tract., 2. ANTERIOR VESTIBULOSPINAL TRACT, , EXTRAPYRAMIDAL TRACTS, , Situation, , Descending tracts of spinal cord other than pyramidal, tracts are called extrapyramidal tracts. Extrapyramidal, tracts are listed in Table 143.3., , Anterior vestibulospinal tract is situated in the anterior, white column, along the periphery of spinal cord lateral, to tectospinal tract., , 1. MEDIAL LONGITUDINAL FASCICULUS, , Origin, , Situation, Medial longitudinal fasciculus descends through posterior part of anterior white column of the spinal cord., , Fibers of this tract arise from medial vestibular nucleus, in medulla oblongata. In fact, anterior vestibulospinal, tract is the extension of medial longitudinal fasciculus., Most of the fibers are uncrossed., , Origin, Actually, this tract is the extension of medial longitudinal, fasciculus of brainstem. Fibers of this tract take origin, from four different areas in brainstem:, i. Vestibular nuclei, ii. Reticular formation, iii. Superior colliculus, iv. Interstitial cells of Cajal., , Extent, Fibers run up to thoracic segments of spinal cord., Course, Fibers of this tract run down from medulla into the, anterior column of spinal cord along the periphery. All, the fibers are uncrossed.
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Chapter 143 t Spinal Cord 819, Termination, Along with fibers of lateral vestibulospinal tract, the, fibers of this tract terminate in anterior motor neurons, directly or through internuncial neurons., , 4. RETICULOSPINAL TRACT, Situation, Reticulospinal tract is situated in the anterior white, column, posterior to anterior vestibulospinal tract., , Function, Function of this tract is explained along with the function, of lateral vestibulospinal tract., 3. LATERAL VESTIBULOSPINAL TRACT, Situation, Lateral vestibulospinal tract occupies the anterior part, of lateral white column of spinal cord., Origin, Fibers of this tract take origin from the lateral, vestibular nucleus in medulla. This nucleus is also, called Deiter nucleus., , Origin, Fibers of this tract arise from the reticular formation, of pons and medulla. Pontine reticular fibers are, uncrossed (direct) and descend in medial part of, anterior column. Fibers from medullary reticular, formation are predominantly uncrossed and only few, fibers are crossed. These fibers descend in lateral part, of anterior column and to some extend in the anterior, part of lateral column., Extent, Fibers of reticulospinal tract extend up to thoracic, segments., , Extent, Fibers of this tract are present throughout the spinal, cord., , Course, From Deiter nucleus, most of the fibers descend, directly through lateral column. Very few fibers cross to, the opposite side before descending., Termination, Fibers of this tract terminate in the anterior motor, neuron, either directly or via internuncial neurons., Functions, Vestibular nuclei receive impulses concerned with, muscle tone and posture from vestibular apparatus, and cerebellum. Vestibular nuclei in turn convey the, impulses to different parts of the body through the, anterior and lateral vestibulospinal tracts., Vestibulospinal tracts are concerned with, adjustment of position of head and body during, angular and linear acceleration., Effect of Lesion, Adjustment of head and body becomes difficult during, acceleration when the vestibulospinal tracts are, affected by lesion., , Termination, Fibers of reticulospinal tract terminate in gamma motor, neurons of anterior gray horn through the internuncial, neuron., Functions, Reticulospinal tract is concerned with control of, movements and maintenance of muscle tone,, respiration and diameter of blood vessels. Pontine, and medullary fibers have opposite effects on these, functions, which are given in Table 143.5., TABLE 143.5: Functions of pontine and medullary, reticulospinal fibers, Function, , Pontine, reticular fibers, , Medullary, reticular fibers, , Control of voluntary, and reflex, Facilitation, movements, , Inhibition, , Control of muscle, tone through, gamma motor, neurons, , Facilitation, , Inhibition, , On respiration, , Favor expiration, , Favor inspiration, , On blood vessels, , Cause, vasoconstriction, , Cause, vasodilatation
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820 Section 10 t Nervous System, Effect of Lesion, , Course, , Lesion of reticulospinal tract causes disturbances in, respiration, blood pressure, movements of body and, muscle tone., , After arising from the red nucleus, the fibers cross the, midline in ventral tegmental decussation and descend, into spinal cord through the reticular formation of pons, and medulla., , 5. TECTOSPINAL TRACT, Termination, Situation, Tectospinal tract is situated in the anterior white, column of spinal cord., , Fibers of rubrospinal tract end in the anterior motor, neurons of the spinal cord via internuncial neurons., Function, , Origin, Nerve fibers of this tract arise from superior colliculus, of midbrain., Extent, Tectospinal tract extends only up to lower cervical, segments., , Course, , Rubrospinal tract exhibits facilitatory influence upon, flexor muscle tone., , 7. OLIVOSPINAL TRACT, Situation, Olivospinal tract is present in lateral white column of, spinal cord., Origin, , After taking origin from superior colliculus, the fibers, cross the midline in dorsal tegmental decussation, and descend in anterior column., , The nerve fibers of the olivospinal tract take origin from, the inferior olivary nucleus, which is present in the, medulla oblongata., , Termination, , Termination, , Fibers of tectospinal tract terminate in the anterior, motor neurons of spinal cord, directly or via internuncial, neurons., , Fibers of this tract terminate in the anterior motor, neurons of spinal cord., Function, , Function, Tectospinal tract is responsible for the movement of, head in response to visual and auditory stimuli., , Functions of the olivospinal tract are not known clearly., It is believed that this tract is involved in reflex movements arising from the proprioceptors., , 6. RUBROSPINAL TRACT, , APPLIED PHYSIOLOGY, , Situation, , Spinal cord injury leads to either temporary or, permanent dysfunction. Dysfunction of spinal cord, occurs because of:, 1. Direct injury due to bullet firing or accidents (on, road, in working place, during communal violence,, etc.), 2. Compression by bone fragments, hematoma or disk, material, 3. Ischemia due to rupture of spinal arteries., During mechanical injury, spinal cord may be cut, into two or one lateral half of the spinal cord may be, damaged or diffused crushing of several segments of, spinal cord may also occur., , Rubrospinal tract is situated in the lateral white, column of spinal cord., Origin, Fibers of this tract arise from large cells (nucleus, magnocellularis) of red nucleus in midbrain., Extent, Nerve fibers of this tract appear in the spinal cord only, up to thoracic segments.
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Chapter 143 t Spinal Cord 821, Accordingly, dysfunction of spinal cord is classified, into four types:, A. Complete transection, B. Incomplete transection, C. Hemisection, D. Diseases of spinal cord., COMPLETE TRANSECTION, OF SPINAL CORD, Complete transection of spinal cord occurs due to:, 1. Bullet injury, which causes dislocation of spinal cord, 2. Accidents, which cause dislocation of spinal cord, or occlusion of blood vessels., Complete transection causes immediate loss of, sensation and voluntary movement below the level of, lesion. In quick transection of spinal cord, the patient, feels himself cut into two. For a while, his mind remains, clear but he feels as if his lower part of the body below, the injury does not exist. It is because his higher, centers remain unaffected but the spinal centers below, the level of injury loose the function., Then the effects (symptoms) of complete, transection of spinal cord start appearing. Effects, occur in three stages:, 1. Stage of spinal shock, 2. Stage of reflex activity, 3. Stage of reflex failure., 1. Stage of Spinal Shock, Stage of spinal shock is the first stage of effects that, occurs immediately after injury. It is also called stage, of flaccidity. Following are the signs and symptoms, that develop during this stage:, i. Paralysis of limbs, Paralysis occurs in two limbs or in all four limbs., Paralysis of limbs depends upon the level of Injury:, a. Injury at the cervical region of the spinal cord leads, to the paralysis of all the four limbs. Paralysis, of all the four limbs is called quadriplegia or, tetraplegia, , b. Injury at the thoracic, lumbar or sacral segments, including cauda equina and conus medullaris, causes paralysis of lower limbs. Paralysis of, lower limbs is called paraplegia., ii. Flaccid paralysis, Paralyzed muscles become flaccid, i.e. loose stiffness, because of loss of tone. This type of paralysis is called, flaccid paralysis., , iii. Loss of reflexes, All the reflexes are lost because of the injury to anterior, and posterior nerve roots., iv. Loss of sensations, All the sensations are lost because of the injury to, posterior nerve roots and sensory neurons in the, posterior gray horn., v. Effect on visceral organs, Some of the visceral organs are also affected;, especially, urinary bladder and rectum are paralyzed., vi. Heart rate, Heart rate is decreased and pulse becomes weak and, thready., vii. Venous return, Venous return is very much decreased. Venous, return depends upon the muscle tone during resting, condition. During activity it depends upon contraction, of skeletal muscle (muscle pump, refer to Chapter 98)., But, in complete transection of spinal cord, muscle, tone is lost and flaccid paralysis occurs. This leads to, decrease in venous return., In addition, the limbs are immobile and smooth, muscles of blood vessels loose the tone. So, the blood, gets accumulated in blood vessels of limbs, particularly, in lower limbs. And, the lower limbs become cold and, blue., , viii. Effect on blood pressure, Effect on blood pressure depends upon the level of, injury:, a. Lesion anywhere below L2 segment, Blood pressure is not affected much because, the sympathetic vasoconstrictor fibers leave, the spinal cord between T1 and L2 segments., b. Lesion at or above T1 segment, All the sympathetic vasoconstrictor fibers, leaving the spinal cord from T1 and L2, segments are transected and are completely, cut off from higher medullary cardiovascular, centers, which regulate the blood pressure., So the blood pressure falls drastically. Mean, arterial pressure falls below 40 mm Hg., Severity of complete transection depends upon, the level of lesion. Complete transection at the level, of cervical region can be very fatal. Because, the, diaphragm and other respiratory muscles are cut off from
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822 Section 10 t Nervous System, respiratory centers. It causes paralysis of respiratory, muscles leading to sudden arrest of breathing., The crushing injury at sacral segments of spinal, cord results in atonic bladder and loss of micturition, reflex (Chapter 57)., In human beings, the stage of spinal shock lasts, for about 3 weeks. In animals the duration of spinal, shock varies in different species. In amphibians like, frog, it lasts only for few minutes. In mammals like, dogs and cats, it lasts for few hours. In monkeys, it, lasts for few days., 2. Stage of Reflex Activity, Stage of reflex activity is also called stage of recovery., After 3 weeks period, depending largely upon the, general health of the patient, the reflex activity begins, to return to the isolated segments of spinal cord below, the level of lesion., Developments taking place in this stage, i. First, the functional activities return to smooth, muscles, ii. Next, the sympathetic tone to blood vessels returns., As the neurons in gray horn act independently of, vasomotor center, the tone in blood vessels is, restored and the blood pressure is also restored, to its normal level., iii. Lastly, after another 3 months, the tone in skeletal, muscle returns. Tone returns to flexor muscles first., So, the flexor muscles of lower limb become less, flabby and offer some resistance to the toes. Though, the tonicity is returned, it is not complete even in, flexor muscles. So, the muscles remain hypotonic., Limbs in this condition tend to adopt a position of, slight flexion and the paralysis is therefore called, the paraplegia in flexion. Limbs cannot support, weight of the body., iv. After few weeks, when tone returns to more, muscles, reflex movements can occur. Flexor, reflexes appear first. To elicit the flexor reflex, a, painful stimulus is required. First reflex, which, usually appears, is the Babinski reflex., v. After a variable period of 1 to 5 weeks of reappearance of flexor reflexes, the extensor reflexes return., Initially, knee jerk returns and then the ankle jerk., vi. In some cases, a widespread reaction can be, elicited by scratching the skin over the lower, limbs or the anterior abdominal wall, depending, upon the level of lesion. This reaction constitutes, the spasm in flexor muscles of both the lower, limbs, evacuation of urinary bladder and profuse, sweating. This is known as the mass reflex., , 3. Stage of Reflex Failure, Though the reflex movements return, muscles below, the level of injury have less power and less resistance., Usually, general condition of the patient starts deteriorating. General infection or toxemia becomes, common. Due to this, the failure of reflex function, develops. The reflexes become more difficult to elicit., The threshold for stimulus increases. Mass reflex is, abolished and the muscles become extremely flaccid, and undergo wasting., INCOMPLETE TRANSECTION, OF SPINAL CORD, If spinal cord is gravely injured, but does not suffer, complete division, the condition is called as incomplete, transection., Symptoms of Incomplete Transection, After incomplete transection of the spinal cord, all the, three stages of complete transection occur., 1. Stage of spinal shock, 2. Stage of reflex activity, 3. Stage of reflex failure., 1. Stage of Spinal Shock, Features are similar to those of complete transection., 2. Stage of Reflex Activity, Features of this stage:, i. Tone returns to extensor muscles first and not to, the flexor muscles. This is because, in incomplete, transection, some of the descending fibers in, lateral column of cord, especially vestibulospinal, and reticulospinal tracts may escape the injury., So, some connections persist between brainstem, and spinal cord. Fibers of vestibulospinal and, reticulospinal tracts mainly reinforce the activity, of extensor motor neurons., Because of this, there is extensor hypertonia, and so, the lower limbs are extended at hip and, knee with toes pointing slightly downwards. This, condition is known as paraplegia in extension., ii. Stretch reflex reappears first. Flexor reflexes, return later. Philipson reflex (clasp-knife reflex), can be elicited., iii. In the upper limb, some resistance is offered, when the arm is flexed at elbow joint passively., That is, the arm cannot be flexed. This resistance, is offered because of the stretch reflex developed, in the triceps muscle. However, if forearm is flexed, forcefully, the resistance to flexion is abolished
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Chapter 143 t Spinal Cord 823, suddenly, leading to quick flexion of arm. This is, called the Philipson reflex or clasp-knife reflex., iv. Mass reflex, which is produced in complete transection, does not occur in incomplete transection, of spinal cord., 3. Stage of Reflex Failure, Features are similar to those of complete transection., HEMISECTION OF SPINAL CORD –, BROWNSÉQUARD SYNDROME, Lesion involving one lateral half of the spinal cord, is called hemisection (Fig. 143.8). It can occur due, to injury during accidents. It can also be produced, experimentally in animals., Symptoms of Hemisection of Spinal Cord, Signs and symptoms, which occur after hemisection of, the spinal cord, constitute Brown-Séquard syndrome., If the hemisection is due to injury, spinal shock, occurs immediately. Muscles loose the tone and become, flaccid. The reflexes are abolished. In case the patient, survives, this stage gradually passes off and certain, signs and symptoms develop. Effects are seen below, the level of lesion and at the level of lesion. Effects in, these areas differ on the same side and opposite side., There are changes in sensory and motor functions., EFFECTS OF HEMISECTION OF SPINAL, CORD BELOW THE LEVEL OF LESION, On the Same Side, , FIGURE 143.8: Hemisection of spinal cord (Brown-Séquard, syndrome). Below the level of lesion: same side = loss of, sensations carried by uncrossed fibers, opposite side = loss, of sensations carried by crossed fibers. At the level of lesion:, same side = complete anesthesia, opposite side = loss of, sensations carried by crossed fibers., , Sensory changes, , Motor changes, , 1. On the same side below the level of lesion, following sensations are lost because these sensations, are carried by the uncrossed fibers of tracts of, Goll and Burdach:, i. Fine touch, ii. Tactile localization, iii. Tactile discrimination, iv. Sensation of vibration, v. Conscious kinesthetic sensation, vi. Stereognosis., 2. Some sensations are not affected because these, sensations are carried by crossed fibers of, spinothalamic tracts. These sensations are:, i. Crude touch, ii. Pain, iii. Temperature., , Motor changes resemble the effects of upper motor, neuron lesion (Chapter 144)., 1. Muscle tone increases, leading to spastic paralysis, 2. Rigidity of limbs occurs, 3. Muscle wastage does not occur, 4. Superficial reflexes are lost, 5. Babinski sign is positive, 6. Deep reflexes are exaggerated, 7. Fall in blood pressure because of loss of vasomotor tone., On the Opposite Side, Sensory changes, 1. On the opposite side, below the level of lesion, the, following sensations are lost completely because,, these sensations are carried by crossed spino, thalamic tracts:
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824 Section 10 t Nervous System, TABLE 143.6: Effects of hemisection (Brown-Séquard syndrome) of spinal cord, , At the level of lesion, , Below the level of lesion, , Level, , Same side, Sensory changes, , Opposite side, Motor changes, , Sensory changes, , Sensations lost, Sensations carried by, uncrossed tracts:, 1. Fine touch, 2. Tactile localization, 3. Tactile discrimination, 4. Vibration sense, 5. Conscious kinesthetic, sensation, 6. Stereognosis, Sensations retained, Sensations carried by crossed, tracts:, 1. Crude touch, 2. Pain, 3. Temperature, , Sensations lost, Sensations carried by, Upper motor neuron lesion, crossed tracts:, type, 1. Crude touch, 2. Pain, 1. Increased tone, 3. Temperature, 2. Spastic paralysis, Sensations retained, 3. Loss of superficial reflexes, Sensations carried by, 4. Exaggeration of deep, uncrossed tracts:, reflexes, 1. Fine touch, 5. Babinski positive sign, 2. Tactile localization, 6. Rigidity in the limbs, 3. Tactile discrimination, 7. No muscular wastage, 4. Vibration sense, 5. Conscious kinesthetic, sensation, 6. Stereognosis, , Complete anesthesia, , Sensations lost, Sensations carried by, crossed tracts:, 1. Crude touch, Lower motor neuron lesion, 2. Pain, type, 3. Temperature, Sensations retained, 1. Loss of muscle tone, Sensations carried by, 2. Flaccid paralysis, uncrossed tracts:, 3. Loss of all reflexes, 1. Fine touch, 4. Wastage of muscle, 2. Tactile localization, 5. Loss of vasomotor tone, 3. Tactile discrimination, 4. Vibration sense, 5. Conscious kinesthetic, sensation, 6. Stereognosis, , i. Crude touch, ii. Pain, iii. Temperature., 2. Following sensations are not affected because,, these sensations are carried by uncrossed tracts, of Goll and Burdach:, i. Fine touch, ii. Tactile localization, iii. Tactile discrimination, iv. Sensation of vibration, v. Conscious kinesthetic sensation, vi. Stereognosis., , Motor changes, , No paralysis, If it occurs:, 1. Very mild, 2. Resembles upper, motor neuron, lesion type, , No paralysis, If it occurs:, 1. Very mild, 2. Resembles lower, motor neuron, lesion type, , pyramidal tract are affected. This is because pyramidal, fibers cross to the opposite side. Paralysis is of upper, motor neuron lesion type., Thus, during hemisection of spinal cord, motor, loss is extensive and sensory loss is less below the, level of lesion on the same side. On the opposite side,, sensory loss is extensive and motor loss is less., EFFECTS OF HEMISECTION OF SPINAL, CORD AT THE LEVEL OF LESION, On the Same Side, , Motor changes, , Sensory changes, , Mostly there may not be any paralysis of muscles., If it occurs, it would be mild as only a few fibers of, , On the same side at the level of hemisection, there is, complete anesthesia. That is, all the sensations are lost
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Chapter 143 t Spinal Cord 825, (Table 143.6). This is because of complete destruction, of the posterior nerve root., , Features, , No motor change occurs. If it occurs, it is very mild, and is similar to the effects of lower motor neuron, lesion (Chapter 144)., , Characteristic features of this disease are the loss, of pain and temperature sensations and muscular, weakness. Severity of the loss of sensations depends, upon the extent of disease in spinal cord., Symptoms of syringomyelia:, 1. If disease is only around central canal, there is loss, of temperature, pain and crude touch sensations, only. It is due to lesion of the fibers crossing through, the anterior gray commissure. Fine touch sensation, is not affected because the fibers of fine touch, pathway are in the posterior white column., 2. If lesion is unilateral, effect occurs only on the, same side, 3. If disease extends to posterior gray horn, all the, sensations are lost. Due to loss of pain and temperature sensations, the affected part is not, withdrawn either reflexly or consciously from a, painful stimulus. So, the affected persons become, prone for injuries. Since, the injury is not perceived, it leads to severe damage to the tissues., 4. If anterior gray horn is affected, there is flaccid, paralysis of muscles. In later stages, both pyramidal, and extrapyramidal tracts are also involved, if the, disease spreads to white matter. It causes spastic, paralysis of limbs, especially in lower limbs, resulting, in spastic paraplegia. Weakness and wasting of, small muscle of limbs occur. Winging of scapula, and scoliosis (lateral curvature of spine) develops., , DISEASES OF SPINAL CORD, , 2. Tabes Dorsalis, , Motor changes, Effects of lower motor neuron lesion occur because the, motor neurons and their fibers leaving the spinal cord, are affected., Motor changes of lower motor neuron lesion are:, 1. Muscles loose the tone and become flaccid and, paralyzed. This type of paralysis with loss of muscle, tone is called flaccid paralysis., 2. All the reflexes are lost, 3. Muscles degenerate and undergo wasting due to, loss of tone, 4. Vasomotor tone is lost., On the Opposite Side, Sensory changes, 1. There is loss of pain, temperature and crude touch, sensations because the crossed spinothalamic, tracts are affected, 2. But tracts of Goll and Burdach are not affected. So,, the sensations carried by these two tracts are not, affected., Motor changes, , 1. Syringomyelia, Syringomyelia is spinal cord disorder characterized, by the presence of fluid-filled cavities in the spinal, cord. Gray matter around the central canal is the most, affected part. So the sensory disturbances are more, pronounced than the motor disturbances., Cause, Stringomyelia occurs due to the over growth of, neuroglial cells in spinal cord accompanied by cavity, formation and accumulation of fluid. Initially, a cavity, appears in gray matter near the central canal of spinal, cord. In later stages, the cavity extends and involves, the surrounding white matter to a variable degree., The disease usually starts in one or two segments., Then, it extends up and down for considerable, distances. Lower cervical and upper thoracic regions, are affected the most., , Tabes dorsalis is another disease of the spinal cord., It is a slowly progressive nervous disorder affecting, both the motor and sensory functions of spinal cord., Cause, It occurs due to the degeneration of posterior (sensory), nerve roots. It usually occurs in syphilis., Posterior nerve roots are affected proximal to the, posterior root ganglia. Ganglia are not affected. Among, the fibers of posterior root, the fibers of lateral division, are affected much. Reason for this type of selective, degeneration is not known., Along with lateral fibers of posterior root, the fibers in, posterior white column of spinal cord are also affected., Features, In tabes dorsalis, both sensory and motor functions are, affected. Following are the features:
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826 Section 10 t Nervous System, Sensations, 1. During the onset of degenerative changes, there is, exaggeration of pain sensation, 2. Then, there is impairment and loss of all sensations, 3. Loss of sensations, particularly pain sensation leads, to deformities of joint. There is no proper support, and movements at the joints become uncontrolled., It is called Charcot joint., 4. Joints enlarge due to inflammation by the development of osteoarthritis., Reflexes, Both superficial and deep reflexes are lost in tabes, dorsalis mostly because of loss of sensations., Voluntary movements, There is lack of coordination of movements (ataxia)., Normal movements like walking also become clumsy., The gait is awkward. Every movement of the limb is, exaggerated while walking. Patient keeps the leg apart,, raises the leg very high and stamps it down forcibly. This, is called stamping gait., Urinary bladder, If sacral segments are affected in tabes dorsalis,, the smooth muscles of the urinary bladder become, hypotonic. Micturition reflexes are lost. And the urinary, bladder becomes atonic bladder (Chapter 57)., 3. Multiple Sclerosis, Multiple sclerosis (MS) is a chronic and progressive, inflammatory disease characterized by demyelination, in brain and spinal cord. It affects the myelinated, nerve fibers of brain, spinal cord and optic nerve, and causes gradual destruction of myelin sheath, (demyelination). When the disease progresses, there, is transection of axons in patches throughout brain, and spinal cord. The term sclerosis refers to scars, (scleroses) in the myelin sheath., Cause, Cause of multiple sclerosis is unknown. It is hypothesized, that multiple sclerosis occurs due to combination and, interaction of environmental factors (chemicals, bacteria, and virus) and genetic factors resulting in abnormal, reactions of immune system. During the process, the, immune system attacks the myelin sheath., , symptoms start appearing. Symptoms become severe, during further progress of the disease., Common initial symptoms:, 1. Mild disturbance in the sensations on face, arms, and legs, 2. Weakness and disturbances in maintenance of, posture, 3. Double vision followed by partial blindness., Other symptoms when the disease progresses:, 1., 2., 3., 4., 5., 6., , Tremor, fatigue and muscle spasms, Speech difficulty, Difficulty in performing day-to-day activities, Bowel problems, Bladder dysfunction, Emotional outbursts like anxiety, anger and, frustration, 7. Short-term memory loss, 8. Complete blindness, 9. Development of suicidal tendency., 4. Disk Prolapse, Intervertebral or spinal disk is the cartilagenous, structure of vertebral column that separates each, vertebra. It is made up of a tough outer fibrous layer, and a soft inner part. Inner part acts as a shock, absorber and cushions the vertebrae while moving. A, small gap in between the adjacent vertebrae allows, nerve roots to enter or leave the spinal cord., Rupture of disk is called disk prolapse. During disk, prolapse, the soft inner material bulges out through, a weak area in the hard outer layer. The bulged disk, material may irritate or compress or damage the, nerve root that passes through the gap between the, vertebrae. Severity of the condition depends upon the, degree of bulging., Causes, 1., 2., 3., 4., 5., , Injury to spinal cord, neck or back, Heavy weight lifting, Sitting for a long time, Sudden violent twisting of the body involving spine, Aging: Because of gradual degeneration of disk, with age. After about 30 years of age, the disk starts, dehydrating. So it is more susceptible for rupture at, the age of 30 to 40 years., , Signs and symptoms, , Symptoms, , Initial attack by multiple sclerosis is often mild or, asymptomatic. As the disease progresses variety of, , Symptoms of disk prolapse include pain and weakness, in the area of prolapse. Most common area of disk
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Chapter 143 t Spinal Cord 827, prolapse is the lower part of vertebral column. If it, compresses the sciatic nerve, the symptoms become, more severe. Pain spreads down the back of leg to, ankle, heel or toes of foot. Lower limb cannot be, lifted sometimes. There is numbness and tingling in, the affected region. Sitting for long period aggravates, the pain and develops other symptoms such as, sneezing, coughing or voiding of urine. Prolonged, , compression of sciatic nerve leads to weakness of leg, muscles., Next common area of disk prolapse is the neck., In this case, the pain is felt in neck, shoulder blade, and armpit. If the nerves supplying upper limbs are, compressed, the pain spreads through the arm up to, the fingers. It also causes stiffness, weakness or tingling, in the upper limbs. Even the movements of fingers or, arm are restricted.
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Somatosensory System, and Somatomotor System, , Chapter, , 144, , SOMATOSENSORY SYSTEM, , , , , , , , DEFINITION AND TYPES OF SENSATIONS, TYPES OF SOMATIC SENSATIONS, SENSORY PATHWAYS, SENSORY FIBERS OF TRIGEMINAL NERVE, LEMNISCUS, APPLIED PHYSIOLOGY, , SOMATOMOTOR SYSTEM, , , , , , , , , , , MOTOR ACTIVITIES OF THE BODY, SOMATOMOTOR SYSTEM, SPINAL CORD AND CRANIAL NERVE NUCLEI, CEREBRAL CORTEX, CEREBELLUM, BASAL GANGLIA, CLASSIFICATION OF MOTOR PATHWAYS, UPPER MOTOR NEURON AND LOWER MOTOR NEURON, APPLIED PHYSIOLOGY, , SOMATOSENSORY SYSTEM, DEFINITION AND TYPES OF SENSATIONS, Somatosensory system is defined as the sensory system, associated with different parts of the body., Sensations are of two types:, 1. Somatic sensations, 2. Special sensations., 1. Somatic Sensations, Somatic sensations are the sensations arising from, skin, muscles, tendons and joints. These sensations, have specific receptors, which respond to a particular, type of stimulus., 2. Special Sensations, Special sensations are the complex sensations for, which the body has some specialized sense organs., , These sensations are usually called special senses., Sensations of vision, hearing, taste and smell are the, special sensations., This chapter deals with somatic sensations., TYPES OF SOMATIC SENSATIONS, Generally, somatic sensations are classified into three, types:, 1. Epicritic sensations, 2. Protopathic sensations, 3. Deep sensations., 1. Epicritic Sensations, Epicritic sensations are the mild or light sensations., Such sensations are perceived more accurately., Epicritic sensations are:, i. Fine touch or tactile sensation (Chapter 143), ii. Tactile localization (Chapter 143)
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Chapter 144 t Somatosensory System and Somatomotor System 829, iii. Tactile discrimination (Chapter 143), iv. Temperature sensation with finer range between, 25°C and 40°C., 2. Protopathic Sensations, Protopathic sensations are the crude sensations. These, sensations are primitive type of sensations., Protopathic sensations are:, i. Pressure sensation (Chapter 143), ii. Pain sensation (Chapter 143), iii. Temperature sensation with a wider range, i.e., above 40°C and below 25°C., , b. Subconscious kinesthetic sensation (Chapter, 143). Impulses of this sensation are called nonsensory impulses., iii. Visceral sensations arising from viscera (Fig., 144.1)., Synthetic Senses, Synthetic senses are the sensations synthesized, at cortical level, by integration of impulses of basic, sensations. Two or more basic sensations are combined, in some of the synthetic senses. Best examples of, synthetic senses are vibratory sensation, stereognosis, and two-point discrimination., SENSORY PATHWAYS, , 3. Deep Sensations, Deep sensations are sensations arising from deeper, structures beneath the skin and visceral organs., Deep sensations are:, i. Sensation of vibration or pallesthesia, which is, the combination of touch and pressure sensation, (Chapter 143), ii. Kinesthetic sensation or kinesthesia: Sensation, of position and movements of different parts of the, body. This sensation arises from the proprioceptors, present in muscles, tendons, joints and ligaments., Proprioceptors are the receptors, which give response during various movements of a joint., Kinesthetic sensation is of two types:, a. Conscious kinesthetic sensation (Chapter 143), , Nervous pathways of sensations are called the, sensory pathways. These pathways carry the impulses, from receptors in different parts of the body to centers, in brain., Sensory pathways are of two types:, 1. Pathways of somatosensory system, 2. Pathways of viscerosensory system., Pathways of somatosensory system convey the, information from sensory receptors in skin, skeletal, muscles and joints. Pathways of this system are, constituted by somatic nerve fibers called somatic, afferent nerve fibers., Pathways of viscerosensory system convey the, information from receptors of the viscera. Pathways of, this system are constituted by visceral or autonomic, fibers., , FIGURE 144.1: Classification of sensations
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830 Section 10 t Nervous System, This chapter deals mainly with the somatosensory, system., Somatosensory Pathways, Each sensory pathway is constituted by two or three, groups of neurons:, i. First order neurons, ii. Second order neurons, iii. Third order neurons., Details of these neurons are given in Chapter 143., Pathways of some sensations like kinesthetic sensation, have only first and second order neurons., Details of pathways are given in Table 144.1., Diagrams of pathways are given in Chapter 143, along, with ascending tracts of spinal cord., SENSORY FIBERS OF TRIGEMINAL NERVE, Trigeminal nerve carries somatosensory information, from face, teeth, periodontal tissues (tissues around, teeth), oral cavity, nasal cavity, cranial dura mater and, major part of scalp to sensory cortex. It also conveys, proprioceptive impulses from the extrinsic muscles of, the eyeball., Origin, Sensory fibers of trigeminal nerve arise from the, trigeminal ganglion situated near temporal bone., Peripheral processes of neurons in this ganglion form, three divisions of trigeminal nerve, namely ophthalmic,, mandibular and maxillary divisions. Cutaneous distribution of the three divisions of trigeminal nerve is, shown in Figure 144.2., Central processes from neurons of trigeminal, ganglion enter pons in the form of sensory root., Termination, After reaching the pons, fibers of sensory root divide into, two groups, namely descending fibers and ascending, fibers. Descending fibers terminate on primary sensory, nucleus and spinal nucleus of trigeminal nerve. Primary, sensory nucleus is situated in pons. Spinal nucleus of, trigeminal nerve is situated below the primary sensory, nucleus and extends up to the upper segments of, spinal cord., Ascending fibers of sensory root terminate in the, mesencephalic nucleus of trigeminal nerve, situated, in brainstem above the level of primary sensory, nucleus (Fig. 144.3)., , FIGURE 144.2: Cutaneous distribution (sensory) of the three, divisions of trigeminal nerve, , Central Connections, Majority of fibers from the primary sensory nucleus, and spinal nucleus of trigeminal nerve ascend in the, form of trigeminal lemniscus and terminate in ventral, posteromedial nucleus of thalamus in the opposite side., Remaining fibers from these two nuclei terminate on, the thalamic nucleus of same side. From thalamus, the, fibers pass via superior thalamic radiation and reach the, somatosensory areas of cerebral cortex., Primary sensory nucleus and spinal nucleus of, trigeminal nerve relay the sensations of touch, pressure,, pain and temperature from the regions mentioned, above., Fibers from mesencephalic nucleus form the, trigeminocerebellar tract that enters spinocerebellum via, the superior cerebellar peduncle of the same side. This, nucleus conveys proprioceptive impulses from facial, muscles, muscles of mastication and ocular muscles., LEMNISCUS, Lemniscus or fillet is the prominent bundle of sensory, nerves in brain., Lemniscus is of four types:, 1. Spinal lemniscus formed by spinothalamic tracts in, medulla oblongata, 2. Lateral lemniscus formed by the fibers carrying, sensation of hearing from cochlear nuclei to inferior, colliculus and medial geniculate body
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–, , Ventral posterolateral, nucleus of thalamus,, reticular formation and, midbrain, , Nucleus of Clarke and, Marginal nucleus –, Fibers form dorsal and, ventral spinocerebellar, tracts, Fast pain – marginal, nucleus in spinal cord, Slow pain – substantia, gelatinosa of Rolando, Fibers form lateral, spinothalamic tract, , Posterior nerve root, ganglion, , Posterior nerve root, ganglion, Fast pain – A δ-fibers, Slow pain – C fibers, , Proprioceptors –, Muscle spindle, Golgi tendon apparatus, , Free nerve endings, , Subconscious, kinesthetic sensation, , Pain, , Ventral posterolateral, nucleus of thalamus, , Conscious kinesthetic, sensation, , Nucleus gracilis and, Nucleus cuneatus –, Fibers form internal, arcuate fibers, , Posterior nerve root, ganglion –, Fibers form, Fasciculus gracilis and, Fasciculus cuneatus, , Ventral posterolateral, nucleus of thalamus, , Substantia gelatinosa –, Fibers form lateral, spinothalamic tract, , Warmth – Ruffini end bulb Posterior nerve root, ganglion, Cold – Krause end bulb, , Temperature, , Proprioceptors –, Muscle spindle, Golgi tendon apparatus, , Ventral posterolateral, nucleus of thalamus, , Chief sensory nucleus –, Fibers form anterior, spinothalamic tract, , Ventral posterolateral, nucleus of thalamus, , Third order neuron in, , Nucleus gracilis and, Nucleus cuneatus –, Fibers form internal, arcuate fibers, , Second order neuron in, , Posterior nerve root, ganglion, , Posterior nerve root, ganglion –, Fibers form, Fasciculus gracilis and, Fasciculus cuneatus, , First order neuron in, , Pacinian corpuscle, , Meissner corpuscles and, Merkel disc, , Receptor, , Pressure, Crude touch, , Fine touch, Tactile localization, Tactile discrimination, Vibratory sensation, Stereognosis, , Sensation, , TABLE 144.1: Sensory pathways, , Sensory cortex, , Anterior lobe of, cerebellum, , Sensory cortex, , Sensory cortex, , Sensory cortex, , Sensory cortex, , Center, , Chapter 144 t Somatosensory System and Somatomotor System 831
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832 Section 10 t Nervous System, , FIGURE 144.3: Diagrammatic representation of trigeminal pathway. Trigeminal lemniscus carries impulses of touch,, pressure, pain and temperature sensations to somatosensory cortex. Trigeminocerebellar tract carries proprioceptive, impulses to spinocerebellum., , 3. Medial lemniscus formed by fibers arising from, nucleus cuneatus and nucleus gracilis, 4. Trigeminal lemniscus formed by fibers from, sensory nuclei of trigeminal nerve. This lemniscus, carries general senses from head, neck, face,, mouth, eyeballs and ears., APPLIED PHYSIOLOGY, Lesions or other nervous disorders in sensory pathway, affect the sensory functions of the body. The effects are, given in Table 144.2., , SOMATOMOTOR SYSTEM, MOTOR ACTIVITIES OF THE BODY, Motor activities of the body depend upon different, groups of tissues of the body., Motor activities are divided into two types:, 1. Activities of skeletal muscles, which are involved in, posture and movement, 2. Activities of smooth muscles, cardiac muscles and, other tissues, which are involved in the functions of, various visceral organs., , Activities of skeletal muscles (voluntary functions), are controlled by somatomotor system, which is, constituted by the somatic motor nerve fibers. Activities, of tissues or visceral organs (involuntary functions), are controlled by visceral or autonomic nervous, system, which is constituted by the sympathetic and, parasympathetic systems. Autonomic nervous system, is described in Chapter 164., This chapter deals with somatomotor system., SOMATOMOTOR SYSTEM, Movements of the body depend upon different groups, of skeletal muscles. Various types of movements or, motor activities brought about by these muscles are:, 1. Execution of smooth, precise and accurate, voluntary movements, 2. Coordination of movements responsible for skilled, activities, 3. Coordination of movements responsible for the, maintenance of posture and equilibrium., Voluntary actions and postural movements are, carried out by not only the simple contraction and, relaxation of skeletal muscles but also the adjustments of tone in these muscles. The execution,
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Chapter 144 t Somatosensory System and Somatomotor System 833, TABLE 144.2: Effects of disorders of sensory pathways, No, , Condition, , Definition, , 1., , Anesthesia, , Loss of all sensations, , 2., , Hyperesthesia, , Increased sensitivity to sensory stimuli, , 3., , Hypoesthesia, , Reduction in sensitivity to stimuli, , 4., , Hemiesthesia, , Loss of all sensations in one side of body, , 5., , Paresthesia, , Abnormal sensations such as tingling, burning, prickling and numbness, , 6., , Hemiparesthesia, , Abnormal sensations in one side of body, , 7., , Dissociated anesthesia, , Loss of some sensations while other sensations are intact, , 8., , General anesthesia, , Loss of all sensations with loss of consciousness produced by anesthetic agents, , 9., , Local anesthesia, , Loss of sensations in a restricted area of the body, , 10., , Spinal anesthesia, , Loss of sensations due to spinal cord lesion or anesthetic agents injected beneath, the coverings of spinal cord, , 11., , Tactile anesthesia, , Loss of tactile sensations, , 12., , Tactile hyperesthesia, , Increased sensitivity to tactile stimuli, , 13., , Analgesia, , Loss of pain sensation, , 14., , Hyperalgesia, , Increased sensitivity to pain stimulus, , 15., , Paralgesia, , Abnormal pain sensation, , 16., , Thermoanesthesia or, thermanesthesia or, thermanalgesia, , Loss of thermal sensation, , 17., , Pallanesthesia, , Loss of sensation of vibration, , 18., , Astereognosis, , Loss of ability to recognize known object with closed eyes due to loss of cutaneous, sensations, , 19., , Illusion, , Mental depression due to misinterpretation of a sensory stimulus, , 20., , Hallucination, , Feeling of a sensation without any stimulus, , planning, coordination and adjustments of movements, of the body are under the influence of different parts, of nervous system, which are together called motor, system. Sensory system of the body also plays a vital, role in the control of movements., Spinal reflexes are responsible for most of the, movements concerned with voluntary actions and, posture. Stimulation of receptor activates the motor, neuron in spinal cord, leading to the contraction of, muscle innervated by spinal motor neuron. Apart from, these reflexes, signals for voluntary motor activities are, also sent from different areas of the brain, particularly, the cerebral cortex to spinal motor neurons., Coordination and control of movements initiated by, cerebral cortex depends upon two factors:, 1. Feedback signals from proprioceptors in muscle, and other sensory receptors, 2. Interaction of other parts of brain such as brainstem,, cerebellum and basal ganglia., Thus, the motor system includes spinal cord and, its nerves, cranial nerves, brainstem, cerebral cortex,, , cerebellum and basal ganglia. Neuronal circuits, between these parts of nervous system, which are, responsible for the motor activities are called the motor, pathways. Classification of motor pathways is given in, the later part of this chapter because the knowledge of, role of different parts of nervous system is essential to, understand the classification of the motor pathways., SPINAL CORD AND CRANIAL, NERVE NUCLEI, Motor Neurons, Activities of skeletal muscles are executed by the, impulses discharged from alpha motor neurons situated, in ventral (anterior) gray horn of spinal cord and nuclei, of many of the cranial nerves present in brainstem., Alpha motor neurons in the spinal cord, which, innervate the extrafusal fibers of skeletal muscles are, responsible for the contraction of muscles in upper, limbs, trunk and lower part of the body. The gamma, motor neurons, which innervate the intrafusal fibers of
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834 Section 10 t Nervous System, muscle, are responsible for the maintenance of muscle, tone., Motor neurons of the cranial nerve nuclei situated in, brainstem send their signals to the muscles of neck and, upper part of trunk via cranial nerves., Final Common Pathway, Activities of a particular skeletal muscle depend upon, the excitation of alpha motor neuron (also known as, lower motor neuron) in the spinal cord or cranial nerve, nuclei. This is the only pathway, through which the, signals from other parts of nervous system reach the, muscles (Fig. 144.4). Hence, the alpha motor neurons, are called ‘final common pathway’ of motor system., Functions of Motor Neurons, Motor neurons responsible for the contraction of, skeletal muscles are arranged topographically in the, ventral gray horn of spinal cord. Neurons situated, in the medial part of ventral gray horn innervate the, muscles near midline of the body called axial muscles, and muscles in the proximal portions of limbs called, proximal muscles. These two types of muscles, are involved in the adjustment of posture and gross, movement. Motor neurons in lateral part of ventral gray, horn innervate the muscles in distal portions of the limbs, called distal muscles. Distal muscles are involved in, the well coordinated skilled voluntary movements., , Motor neurons in cranial nerve nuclei of brainstem, innervate the extrinsic muscles of eyeball and muscles, of face, tongue, neck and upper part of trunk. These, muscles are concerned with ocular movements and, movements of facial expressions, chewing, swallowing, and movements of head and shoulder. Motor neurons, are situated in the nuclei of cranial nerves III, IV, V, VI,, VII, IX, X, XI and XII., CEREBRAL CORTEX, Cortical areas concerned with origin of motor signals, are the primary motor area, premotor area and, supplementary motor area in frontal lobe and sensory, area in the parietal lobe. Details of the cortical areas are, given in Chapter 152., Cortical areas send their output signals to spinal, cord via corticospinal tracts and to brainstem via, corticobulbar tracts. About 30% of the fibers forming, corticospinal and corticobulbar tracts take their origin, from primary and supplementary motor cortex, 30%, from premotor area and remaining 40% from parietal, lobe particularly from somatosensory area., CEREBELLUM, Cerebellum plays an important role in planning,, programming and integrating the skilled voluntary, movements. It is also concerned with the maintenance, of muscle tone, posture and equilibrium. Cerebellum, , FIGURE 144.4: Final common pathway
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Chapter 144 t Somatosensory System and Somatomotor System 835, receives impulses from proprioceptors of muscle,, vestibular apparatus, cerebral cortex, brainstem and, basal ganglia. It interprets these impulses and sends, signals to motor cortex, reticular formation and nuclei, of brainstem., Role of cerebellum in motor functions is described, in detail in Chapter 150., , Lateral and Medial Motor Systems, , BASAL GANGLIA, , Fibers of this system terminate on motor neurons, situated in lateral part of ventral gray horn in spinal, cord (directly or via interneurons) and on equivalent, motor neurons of cranial nerve nuclei in brainstem., Components of lateral system:, 1. Lateral corticospinal tract, which arises from, different areas of cerebral cortex and terminates, in the alpha motor neurons situated in lateral part, of ventral gray horn of spinal cord. Other details of, this tract are given in Chapter 143., 2. Rubrospinal tract, which arises from red nucleus in, midbrain (Chapter 143), 3. Part of corticobulbar tract, which arises from different, areas of frontal and parietal lobes of cerebral cortex, along with corticospinal tracts. Part of corticobulbar, tract belonging to lateral motor system terminates, on the nucleus of hypoglossal nerve and motor, nucleus of facial nerve. Fibers from hypoglossal, nerve innervate the muscles of tongue. Fibers from, motor nucleus of facial nerve innervate the muscles, of lower part of face., , Basal ganglia play an important role in the coordination of skilled movements, regulation of automatic, associated movements and control of muscle tone, by sending output signals to motor cortex, reticular, formation and spinal cord. Functions of basal ganglia, are explained in Chapter 151., CLASSIFICATION OF MOTOR PATHWAYS, There are two methods to classify the motor pathways., In the first method of classification, motor pathways, are divided into pyramidal and extrapyramidal tracts. In, the second method, motor pathways are classified into, lateral and medial systems., Pyramidal and Extrapyramidal Pathways, Motor pathways are classified into pyramidal and extrapyramidal tracts, depending upon the situation of their, fibers in medulla oblongata., Pyramidal tracts, Pyramidal tracts are those fibers which form the pyramids in upper part of medulla. Pyramidal tracts are, the anterior and lateral corticospinal tracts. These, tracts control the voluntary movements of the body, (Chapter 143)., Extrapyramidal tracts, Motor pathways other than pyramidal tracts are known, as extrapyramidal tracts., Extrapyramidal tracts are:, 1. Medial longitudinal fasciculus, 2. Anterior and lateral vestibulospinal tracts, 3. Reticulospinal tract, 4. Tectospinal tract, 5. Reticulospinal tract, 6. Rubrospinal tract, 7. Olivospinal tract., Extrapyramidal tracts are concerned with the regulation of tone, posture and equilibrium (Chapter 143)., , Depending upon the location or termination, motor, pathways are divided into two categories, namely the, lateral system or pathway and the medial system or, pathway. Lateral motor system is phylogenetically new, and medial motor system is old., Lateral motor system, , Functions of lateral motor system:, 1. Lateral corticospinal tract activates the muscles of, distal portions of limbs and regulates the skilled, voluntary movements, 2. Rubrospinal tract facilitates the tone in the muscles,, particularly the flexor muscles, 3. Corticobulbar fibers of lateral system are concerned, with the movements of expression in lower part of, face and movements of tongue., Medial motor system, Fibers of medial motor system terminate on motor neurons, situated in the medial part of ventral gray horn of spinal, cord (via interneurons) and on equivalent motor neurons, of cranial nerve nuclei, situated in the brainstem., Components of medial motor system:, 1. Anterior corticospinal tract, which arises from different areas of cerebral cortex and terminates in the, alpha motor neurons situated in medial part of, ventral gray horn of spinal cord (Chapter 143).
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836 Section 10 t Nervous System, 2. Part of corticobulbar fibers of medial system, which, arises from different areas of frontal and parietal, lobes of cerebral cortex along with corticospinal, tracts. Fibers of corticobulbar tract belonging to, medial motor system innervate the muscles of trunk, and limbs, muscles of jaw and muscles of upper, part of face., 3. Lateral and medial vestibulospinal tracts that arise, from lateral vestibular nucleus and medial vestibular, nucleus, respectively (Chapter 143), 4. Reticulospinal tract, which arises from reticular, formation in brainstem (Chapter 143), 5. Tectospinal tract, which takes origin from superior, colliculus of midbrain (Chapter 143)., Functions of medial motor system:, 1. Anterior corticospinal tract is responsible for the, maintenance of posture and equilibrium, 2. Fibers of corticobulbar tract belonging to medial, motor system, innervating muscles of upper part, of trunk are involved in the maintenance of posture, and equilibrium. Fibers innervating muscles of jaw, and face are involved in the movements of chewing, and movements of eyebrow., 3. Vestibulospinal tract is concerned with the adjustment of position of head and body during angular, and linear acceleration, 4. Pontine fibers of reticulospinal tract facilitate the, tone of extensor muscles and regulate the postural, reflexes. However, medullary fibers of this tract, inhibit the tone of the muscles involved in postural, movements., 5. Tectospinal tract is responsible for the movement of, head in response to visual and auditory stimuli., , UPPER MOTOR NEURON AND, LOWER MOTOR NEURON, Neurons of the motor system are divided into upper, motor neurons and lower motor neurons, depending, upon their location and termination., Upper Motor Neuron, Upper motor neurons are the neurons in higher centers, of brain, which control the lower motor neurons., Upper motor neurons are of three types:, 1. Motor neurons in cerebral cortex. Fibers of these, neurons form corticospinal (pyramidal) and, corticobulbar tracts., 2. Neurons in basal ganglia and brainstem nuclei, 3. Neurons in cerebellum., Motor neurons in cerebral cortex, which give origin, to pyramidal tracts belong to the pyramidal system and, the remaining motor neurons belong to extrapyramidal, system., Some controversy exists in including the neurons, of extrapyramidal system under the category of upper, motor neurons. However, considering in terms of the, definition, neurons other than lower motor neurons are, to be named as upper motor neurons., Lower Motor Neuron, Lower motor neurons are the anterior gray horn cells in, spinal cord and motor neurons of cranial nerve nuclei,, situated in brainstem, which innervate the muscles, directly., Thus, the lower motor neurons constitute ‘final, common pathway’ of motor system. Lower motor neurons, are under the influence of upper motor neurons., , TABLE 144.3: Effects of upper motor neuron lesion and lower motor neuron lesion, , Clinical, confirmation, , Clinical, observation, , Effects, , Upper motor neuron lesion, , Lower motor neuron lesion, , 1. Muscle tone, , Hypertonia, , Hypotonia, , 2. Paralysis, , Spastic type of paralysis, , Flaccid type of paralysis, , 3. Wastage of muscle, , Wastage of muscle occurs, , Wastage of muscle occurs, , 4. Superficial reflexes, , Lost, , Lost, , 5. Plantar reflex, , Abnormal plantar reflex – Babinski sign, , Absent, , 6. Deep reflexes, , Exaggerated, , Lost, , 7. Clonus, , Present, , Absent, , 8. Electrical activity, , Normal, , Absent, , 9. Muscles affected, , Groups of muscles are affected, , Individual muscles are affected, , Absent, , Present, , 10. Fascicular twitch in EMG
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Chapter 144 t Somatosensory System and Somatomotor System 837, TABLE 144.4: Types of paralysis, Paralysis, , Parts of the body affected, , Causes, , Monoplegia, , Paralysis of one limb, , Isolated damage of central nervous system or peripheral, nervous system, , Diplegia, , Paralysis of both the upper limbs or, both the lower limbs, , Isolated damage of brain, , Hemiplegia, , Paralysis of upper limb and lower, limb on one side of the body, , Lesion in motor cortex and corticospinal tracts in posterior limb, of internal capsule on the side opposite to the paralysis, , Paraplegia, , Paralysis of lower half of the body, , Injury to lower part of spinal cord, , Paralysis of all the four limbs, , Injury to upper part of spinal cord (shoulder level or above, at, which the motor nerves of upper limbs leave the spinal cord), , Quadriplegia or, tetraplegia, , APPLIED PHYSIOLOGY, Effects of Motor Neuron Lesions, Effects of lesions of upper motor neurons and lower, motor neurons are given in Table 144.3. Effects of lower, motor neuron lesion are the loss of muscle tone and, flaccid paralysis., Effects of upper motor neuron lesion depends, upon the type of neuron involved. Effects of upper, motor neuron lesion are:, 1. Lesion in pyramidal system causes hypertonia and, spastic paralysis. Spastic paralysis involves only, one group of muscles, particularly the extensor, muscles., 2. Lesion in basal ganglia produces hypertonia and, rigidity involving both flexor and extensor muscles, , 3. Lesion in cerebellum causes hypotonia, muscular, weakness and incoordination of movements., Paralysis, Paralysis is defined as the complete loss of strength, and functions of muscle group or a limb., Causes for paralysis, Common causes for paralysis are trauma, tumor,, stroke, cerebral palsy (condition caused by brain injury, immediately after birth), multiple sclerosis (Chapter, 143) and neurodegenerative diseases., Types of paralysis, Paralysis of muscles in the body depends upon type, and location of motor neurons affected by the lesion., Different types of paralysis are given in Table 144.4.
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Chapter, , Physiology of Pain, , , , , , 145, , INTRODUCTION, BENEFITS OF PAIN SENSATION, COMPONENTS OF PAIN SENSATION, PATHWAYS OF PAIN SENSATION, , , , , , FROM SKIN AND DEEPER STRUCTURES, FROM FACE, FROM VISCERA, FROM PELVIC REGION, , VISCERAL PAIN, , , CAUSES OF VISCERAL PAIN, , REFERRED PAIN, , , , , DEFINITION, EXAMPLES OF REFERRED PAIN, MECHANISM OF REFERRED PAIN, , NEUROTRANSMITTERS INVOLVED IN PAIN SENSATION, ANALGESIA SYSTEM, , , ANALGESIC PATHWAY, , GATE CONTROL THEORY, APPLIED PHYSIOLOGY, , INTRODUCTION, Pain is defined as an unpleasant and emotional, experience associated with or without actual tissue, damage. Pain sensation is described in many ways like, sharp, pricking, electrical, dull ache, shooting, cutting,, stabbing, etc. Often it induces crying and fainting., Pain is produced by real or potential injury to the, body. Often it is expressed in terms of injury. For example,, pain produced by fire is expressed as burning sensation;, pain produced by severe sustained contraction of, skeletal muscles is expressed as cramps., Pain may be acute or chronic. Acute pain is a, sharp pain of short duration with easily identified cause., Often it is localized in a small area before spreading to, neighboring areas. Usually it is treated by medications., Chronic pain is the intermittent or constant pain with, , different intensities. It lasts for longer periods. It is, somewhat difficult to treat chronic pain and it needs, professional expert care., , BENEFITS OF PAIN SENSATION, Pain is an important sensory symptom. Though it is, an unpleasant sensation, it has protective or survival, benefits such as:, 1. Pain gives warning signal about the existence of, a problem or threat. It also creates awareness of, injury., 2. Pain prevents further damage by causing reflex, withdrawal of the body from the source of injury, 3. Pain forces the person to rest or to minimize the, activities thus enabling rapid healing of injured part, 4. Pain urges the person to take required treatment to, prevent major damage.
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Chapter 145 t Physiology of Pain 839, , COMPONENTS OF PAIN SENSATION, Pain sensation has two components:, 1. Fast pain, 2. Slow pain., Fast pain is the first sensation whenever a pain, stimulus is applied. It is experienced as a bright, sharp, and localized pain sensation. Fast pain is followed by, the slow pain, which is experienced as a dull, diffused, and unpleasant pain., Receptors for both the components of pain are, same, i.e. the free nerve endings. But, afferent nerve, fibers are different. Fast pain sensation is carried by Aδ, fibers and slow pain sensation is carried by C type of, nerve fibers., , PATHWAYS OF PAIN SENSATION, Pain sensation from various parts of body is carried to, brain by different pathways which are:, 1. Pathway from skin and deeper structures, 2. Pathway from face, 3. Pathway from viscera, 4. Pathway from pelvic region., , from these neurons ascend in the form of the lateral, spinothalamic tract., Fast pain fibers, Fibers of fast pain arise from neurons of marginal, nucleus. Immediately after taking origin, the fibers cross, the midline via anterior gray commissure, reach the, lateral white column of the opposite side and ascend., These fibers form the neospinothalamic fibers in lateral, spinothalamic tract. These nerve fibers terminate in, ventral posterolateral nucleus of thalamus. Some of, the fibers terminate in ascending reticular activating, system of brainstem., Slow pain fibers, Fibers of slow pain, which arise from neurons of sub, stantia gelatinosa, cross the midline and run along, the fibers of fast pain as paleospinothalamic fibers, in lateral spinothalamic tract. One fifth of these fibers, terminate in ventral posterolateral nucleus of thalamus., Remaining fibers terminate in any of the following, areas:, i. Nuclei of reticular formation in brainstem, ii. Tectum of midbrain, iii. Gray matter surrounding aqueduct of Sylvius., , 1. FROM SKIN AND DEEPER STRUCTURES, Third Order Neurons, Receptors, Receptors of pain sensation are the free nerve endings,, which are distributed throughout the body., First Order Neurons, First order neurons are the cells in posterior nerve root, ganglia, which receive the impulses of pain sensation, from pain receptors through their dendrites. These, impulses are transmitted to spinal cord through the, axons of these neurons., Fast pain fibers, Fast pain sensation is carried by Aδ type afferent fibers, which synapse with neurons of marginal nucleus in the, posterior gray horn., Slow pain fibers, Slow pain sensation is carried by C type afferent fibers,, which synapse with neurons of substantia gelatinosa of, Rolando in the posterior gray horn (Fig. 143.4)., Second Order Neurons, Neurons of marginal nucleus and substantia gelatinosa, of Rolando form the second order neurons. Fibers, , Third order neurons of pain pathway are the neurons, in:, i. Thalamic nucleus, ii. Reticular formation, iii. Tectum, iv. Gray matter around aqueduct of Sylvius., Axons from these neurons reach the sensory, area of cerebral cortex (Fig. 145.2). Some fibers from, reticular formation reach hypothalamus., Center for Pain Sensation, Center for pain sensation is in postcentral gyrus of pari, etal cortex. Fibers reaching hypothalamus are concerned, with arousal mechanism due to pain stimulus., 2. FROM FACE, Pain sensation from face is carried by trigeminal nerve, (Chapter 144)., 3. FROM VISCERA, Pain sensation from thoracic and abdominal viscera, is transmitted by sympathetic (thoracolumbar) nerves., Pain from esophagus, trachea and pharynx is carried, by vagus and glossopharyngeal nerves.
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840 Section 10 t Nervous System, 4. FROM PELVIC REGION, Pain sensation from deeper structures of pelvic region, is conveyed by sacral parasympathetic nerves., , VISCERAL PAIN, Pain from viscera is unpleasant. It is poorly localized., CAUSES OF VISCERAL PAIN, 1. Ischemia, Substances released during ischemic reactions such as, bradykinin and proteolytic enzymes stimulate the pain, receptors of viscera., 2. Chemical Stimuli, Chemical substances like acidic gastric juice, leak from, ruptured ulcers into peritoneal cavity and produce pain., 3. Spasm and Overdistention of Hollow Organs, Spastic contraction of smooth muscles in gastrointestinal, tract and other hollow organs of viscera cause pain by, stimulating the free nerve endings. Overdistention of, hollow organs also causes pain., , REFERRED PAIN, DEFINITION, Referred pain is the pain that is perceived at a site, adjacent to or away from the site of origin. Deep pain, and some visceral pain are referred to other areas. But,, superficial pain is not referred., EXAMPLES OF REFERRED PAIN, 1. Cardiac pain is felt at inner part of left arm and left, shoulder (Fig. 145.1), 2. Pain in ovary is referred to umbilicus, 3. Pain from testis is felt in abdomen, 4. Pain in diaphragm is referred to shoulder, 5. Pain in gallbladder is referred to epigastric region, 6. Renal pain is referred to loin., , FIGURE 145.1: Sites of referred pain, , A dermatome includes all the structures or parts of, the body, which are innervated by afferent nerve fibers, of one dorsal root. For example, the heart and inner, aspect of left arm originate from the same dermatome., So, the pain in heart is referred to left arm., , NEUROTRANSMITTERS INVOLVED, IN PAIN SENSATION, , MECHANISM OF REFERRED PAIN, , Glutamate and substance P are the neurotransmitters, secreted by pain nerve endings. Aδ afferent fibers,, which transmit impulses of fast pain secrete glutamate., The C type fibers, which transmit impulses of slow pain, secrete substance P., , Dermatomal Rule, , ANALGESIA SYSTEM, , According to dermatomal rule, pain is referred to a, structure, which is developed from the same dermatome, from which the pain producing structure is developed., , Analgesia system means the pain control system., Body has its own analgesia system in brain, which, provides a shortterm relief from pain. It is also called
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Chapter 145 t Physiology of Pain 841, endogenous analgesic system. Analgesia system, has got its own pathway through which it blocks the, synaptic transmission of pain sensation in spinal, cord and thus attenuates the experience of pain. In, fact analgesic drugs such as opioids act through this, system and provide a controlled pain relief., , ANALGESIC PATHWAY, Analgesic pathway that interferes with pain transmission, is often considered as descending pain pathway, the, ascending pain pathway being the afferent fibers that, transmit pain sensation to the brain (Fig. 145.2)., Role of Analgesic Pathway in Inhibiting, Pain Transmission, 1. Fibers of analgesic pathway arise from frontal lobe, of cerebral cortex and hypothalamus, 2. These fibers terminate in the gray matter surround, ing the third ventricle and aqueduct of Sylvius (peri, aqueductal gray matter), 3. Fibers from here descend down to brainstem and, terminate on:, i. Nucleus raphe magnus, situated in reticular, formation of lower pons and upper medulla, ii. Nucleus reticularis, paragigantocellularis situated, in medulla, 4. Fibers from these reticular nuclei descend through, lateral white column of spinal cord and reach the, synapses of the neurons in afferent pain pathway, situated in anterior gray horn, Synapses of the afferent pain pathway are, between:, i. Aδ type afferent fibers and neurons of marginal, nucleus, ii. C type afferent fibers and neurons of substantia, gelatinosa of Rolando., 5. At synaptic level, analgesic fibers release neuro, transmitters and inhibit the pain transmission, before being relayed to brain., Neurotransmitters of Analgesic Pathway, Neurotransmitters released by the fibers of analgesic, pathway are serotonin and opiate receptor substances, namely enkephalin, dynorphin and endorphin., , GATE CONTROL THEORY, Psychologist Ronald Melzack and the anatomist Patrick, Wall proposed the gate control theory for pain in 1965 to, explain the pain suppression., According to them, the pain stimuli transmitted by, afferent pain fibers are blocked by gate mechanism, , FIGURE 145.2: Pain pathway and analgesic pathway, , located at the posterior gray horn of spinal cord. If the, gate is opened, pain is felt. If the gate is closed, pain is, suppressed., Mechanism of Gate Control at Spinal Level, 1. When pain stimulus is applied on any part of body,, besides pain receptors, the receptors of other, sensations such as touch are also stimulated
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842 Section 10 t Nervous System, 2. When all these impulses reach the spinal cord, through posterior nerve root, the fibers of touch, sensation (posterior column fibers) send collaterals, to the neurons of pain pathway, i.e. cells of marginal, nucleus and substantia gelatinosa, 3. Impulses of touch sensation passing through these, collaterals inhibit the release of glutamate and, substance P from the pain fibers, 4. This closes the gate and the pain transmission is, blocked (Fig. 145.3)., , Role of Brain in Gate Control Mechanism, According to Melzack and Wall, brain also plays some, important role in the gate control system of the spinal, cord as follows:, 1. If the gates in spinal cord are not closed, pain signals, reach thalamus through lateral spinothalamic, tract, 2. These signals are processed in thalamus and sent, to sensory cortex, , FIGURE 145.3: Gate control system
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Chapter 145 t Physiology of Pain 843, 3. Perception of pain occurs in cortical level in context, of the person’s emotional status and previous, experiences, 4. The person responds to the pain based on the, integration of all these information in the brain., Thus, the brain determines the severity and extent, of pain., 5. To minimize the severity and extent of pain, brain, sends message back to spinal cord to close the gate, by releasing pain relievers such as opiate peptides, 6. Now the pain stimulus is blocked and the person, feels less pain., Significance of Gate Control, Thus, gating of pain at spinal level is similar to pre, synaptic inhibition. It forms the basis for relief of pain, through rubbing, massage techniques, application of, , ice packs, acupuncture and electrical analgesia. All, these techniques relieve pain by stimulating the re, lease of endogenous pain relievers (opioid peptides),, which close the gate and block the pain signals., , APPLIED PHYSIOLOGY, 1. Analgesia, Analgesia means loss of pain sensation., 2. Hyperalgesia, Hyperalgesia is defined as the increased sensitivity to, pain sensation., 3. Paralgesia, Abnormal pain sensation is called paralgesia.
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Chapter, , Brainstem, , 146, , , , , , , INTRODUCTION, MEDULLA OBLONGATA, PONS, MIDBRAIN, , , , TECTUM, CEREBRAL PEDUNCLES, , INTRODUCTION, , 4. Vomiting Center, , Brainstem is the part of brain formed by medulla, oblongata, pons and midbrain. Brainstem contains, ascending and descending tracts between brain and, spinal cord. It also contains many centers for regulation, of vital functions in the body., , Vomiting center induces vomiting during irritation or, inflammation of gastrointestinal (GI) tract., , MEDULLA OBLONGATA, Medulla oblongata or medulla is the lowermost part, of brain. It is situated below pons and is continued, downwards as spinal cord. Medulla forms the main, pathway for ascending and descending tracts of the, spinal cord. It also has many important centers which, control the vital functions., , 5. Superior and Inferior Salivatory Nuclei, Salivatory nuclei control the secretion of saliva., 6. Cranial Nerve Nuclei, , Dorsal and ventral group of neurons form the medullary, respiratory centers, which maintain normal rhythmic, respiration., , Nuclei of 12th, 11th, 10th and some nuclei of 8th, and 5th cranial nerves are located in the medulla, oblongata. 12th cranial (hypoglossal) nerve controls the, movements of tongue. 11th cranial (accessory) nerve, controls the movements of shoulder and 10th cranial, (vagus) nerve controls almost all the vital functions, in the body, viz. cardiovascular system, respiratory, system, GI system, etc. 8th cranial nerve (the cochlear, division of this nerve), which has the relay in medulla, oblongata, is concerned with the auditory function., , 2. Vasomotor Center, , 7. Vestibular Nuclei, , Vasomotor center controls blood pressure and heart, rate., , Vestibular nuclei contain the second order neurons, of vestibular nerve. There are four vestibular nuclei,, situated in the rostral part of medulla and caudal part, of pons, namely superior, medial, lateral and inferior, vestibular nuclei. Medial and inferior vestibular nuclei, extend into medulla., , 1. Respiratory Centers, , 3. Deglutition Center, Deglutition center regulates the pharyngeal and eso, phageal stages of deglutition.
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Chapter 146 t Brainstem 845, All the medullary centers and nuclei of cranial nerves, are controlled by higher centers, situated in cerebral, cortex and hypothalamus., , Inferior colliculus is the center for auditory reflexes., Stimulation of this also produces reflex vocalization., CEREBRAL PEDUNCLES, , PONS, Pons forms a bridge between medulla and midbrain., Functions of Pons, 1. Axons of pontine nuclei join to form the middle, cerebellar peduncle or the brachium pontis. Pons, forms the pathway that connects cerebellum with, cerebral cortex., 2. Pyramidal tracts pass through the pons, 3. Medial lemniscus is joined by the fibers of 10th, 9th,, 7th and 5th cranial nerves in pons, 4. Nuclei of 8th, 7th, 6th and 5th cranial nerves are, located in pons, 5. Pons contains the pneumotaxic and apneustic, centers for regulation of respiration, 6. It also contains the vestibular nuclei, which are, already mentioned in medulla oblongata., , MIDBRAIN, Midbrain lies between pons and diencephalon. It, consists of two parts:, A. Tectum, B. Cerebral peduncles., TECTUM, Tectum is formed by two structures:, 1. Superior colliculus, 2. Inferior colliculus., 1. Superior Colliculus, Superior colliculus is a small structure and is an, important center for reflexes. Through tectospinal, tract, superior colliculus controls the movements of, the eyes, head, trunk and limbs, in response to visual, impulses. Efferent fibers from superior colliculus going, to the nucleus of III cranial (oculomotor) nerve cause, constriction of pupil during light reflex. Thus, it forms, the center for light reflex. Superior colliculus also, receives afferents from optic tract, which helps in the, integration of optical and postural reflexes., 2. Inferior Colliculus, Inferior colliculus consists of single layer of neurons to, which the lateral lemniscus (auditory fibers) synapses., , Cerebral peduncles include:, 1. Basis pedunculi, 2. Substantia nigra, 3. Tegmentum, which includes red nucleus., 1. Basis Pedunculus, Basis pedunculus consists of pyramidal tract fibers, in the middle, temporopontine fibers laterally and, frontopontine fibers medially., 2. Substantia Nigra, Substantia nigra is situated below the red nucleus., Substantia nigra is considered as one of the components, of basal ganglia (Chapter 151)., 3. Tegmentum, Tegmentum lies dorsal to substantia nigra and is actually, the upward continuation of the reticular formation in, pons. Tegmentum comprises three decussations and, red nucleus., Decussations in tegmentum, i. Superior cerebellar peduncle, which is formed, by fibers between cerebellum and other parts of, CNS. These fibers are predominantly efferent, fibers from dentate nucleus of cerebellum; few, fibers are from other cerebellar nuclei such as, nucleus globosus and nucleus emboliformis., ii. Forel decussation, which is due to the crossing, of rubrospinal tracts from either side, iii. Meynert decussation, which is due to the, crossing of medial longitudinal bundle that is, formed by efferent fibers of 3rd, 4th and 6th, cranial nerves., Red Nucleus, Red nucleus is a large oval or round mass of gray, matter, extending between the superior colliculus and, hypothalamus., Parts of red nucleus, Red nucleus has two parts:, 1. Nucleus magnocellularis, which is formed by large, cells. Fibers from this form the rubrospinal and, rubrobulbar tracts.
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846 Section 10 t Nervous System, , FIGURE 146.1: Afferent connections of red nucleus, , 2. Nucleus parvocellularis, which is formed by smaller, cells. Fibers from this form mainly the rubroreticular, tract., Connections of red nucleus, Afferent connections: Red nucleus receives fibers, from:, 1. Nucleus parvocellularis, which receives fibers from, motor cortex (area 6) – corticorubral fibers (Fig., 146.1), 2. Nucleus magnocellularis, which receives fibers, from motor cortex (area 6) – pallidorubral fibers, 3. Nucleus magnocellularis, which receives fibers from, dentate nucleus (of opposite side) – cerebellorubral, or dentatorubral tract., Efferent connections: Red nucleus sends efferent, fibers to various parts of brain and spinal cord:, 1. Rubrospinal tract to spinal cord (Fig. 146.2), 2. Rubrobulbar tract to medulla, 3. Rubroreticular fibers to reticular formation, 4. Rubrothalamic tract to lateral ventral nucleus of, thalamus, 5. Rubroolivary tract to inferior olivary nucleus, 6. Fibers to nuclei of 3rd, 4th and 6th cranial nerves., , FIGURE 146.2: Efferent connections of red nucleus, , Functions of red nucleus, 1. Control of muscle tone: Because of its connections, with cerebellum, vestibular apparatus and skeletal, muscle, the red nucleus plays an important role in, facilitating the muscle tone., 2. Control of complex muscular movements:, Red nucleus controls the complex muscular, movements. It plays an important role in the, integration of various impulses received from many, important areas of brain., 3. Control of righting reflexes: Red nucleus is the, center for all righting reflexes except optical righting, reflexes (Chapter 157)., 4. Control of movements of eyeball: Through its, efferent connections with nuclei of 3rd, 4th and 6th, cranial nerves, red nucleus plays an important role, in the control of ocular movements (Chapter 165)., 5. Control of skilled movements: Red nucleus plays, an important role in controlling the skilled muscular, movements by its connections with spinal cord, and cerebral cortex.
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Chapter, , Thalamus, , 147, , INTRODUCTION, THALAMIC NUCLEI, , , , ANATOMICAL CLASSIFICATION, PHYSIOLOGICAL CLASSIFICATION, , CONNECTIONS OF THALAMIC NUCLEI, THALAMIC RADIATIONS, , , , , , ANTERIOR (FRONTAL) PEDUNCLE OR RADIATION, SUPERIOR (CENTROPARIETAL) PEDUNCLE OR RADIATION, POSTERIOR (OCCIPITAL) PEDUNCLE OR RADIATION, INFERIOR (TEMPORAL) PEDUNCLE OR RADIATION, , FUNCTIONS OF THALAMUS, , , , , , , , , RELAY CENTER, CENTER FOR PROCESSING OF SENSORY INFORMATION, CENTER FOR DETERMINING QUALITY OF SENSATIONS, CENTER FOR SEXUAL SENSATIONS, ROLE IN AROUSAL AND ALERTNESS REACTIONS, CENTER FOR REFLEX ACTIVITY, CENTER FOR INTEGRATION OF MOTOR ACTIVITY, , APPLIED PHYSIOLOGY, , , , THALAMIC LESION, THALAMIC SYNDROME, , INTRODUCTION, Thalamus is a large ovoid mass of gray matter, situated, bilaterally in diencephalon. Both thalami form 80% of, diencephalon. Thalami on both sides are connected in, their rostral portions by means of an intermediate mass., Caudal portions are more widely separated by corpora, quadrigemina., , 1., 2., 3., 4., 5., , Midline nuclei, Intralaminar nuclei, Medial mass of nuclei, Lateral mass of nuclei, Posterior group of nuclei., , 1. Midline Nuclei, , THALAMIC NUCLEI, Thalamic nuclei are classified by two methods:, A. Anatomical classification, B. Physiological classification., , Midline nuclei are a group of small nuclei, situated, on the medial surface of thalamus near the midline, (Fig. 147.1)., , ANATOMICAL CLASSIFICATION, , 2. Intralaminar Nuclei, , Thalamus on each side is divided into five main nuclear, groups by ‘Y’-shaped internal medullary lamina., , Intralaminar nuclei are smaller nuclei present in the, medullary septum of thalamus.
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848 Section 10 t Nervous System, 3. Medial Mass of Nuclei, Medial mass of nuclei are situated medial to septum, and it comprises two nuclei:, i. Anterior nucleus, ii. Dorsomedial nucleus., 4. Lateral Mass of Nuclei, This group of nuclei are situated lateral to septum., Lateral mass of nuclei are again divided into two, subgroups:, i. Dorsal group of lateral mass with two nuclei:, a. Dorsolateral nucleus, b. Posterolateral nucleus, ii. Ventral group of lateral mass with three nuclei:, a. Ventral anterior nucleus, b. Ventral lateral nucleus, c. Ventral posterior nucleus. It consists of two, parts:, • Ventral posterolateral nucleus, • Ventral posteromedial nucleus., 5. Posterior Group of Nuclei, Posterior group of nuclei are the continuation of lateral, mass of nuclei. It has two subgroups:, , i. Pulvinar, ii. Metathalamus which consists of two structures:, a. Medial geniculate body, b. Lateral geniculate body., Thalamic reticular nucleus, Thalamus also includes thalamic reticular nucleus,, which is a thin layer of neurons covering the lateral, aspect of thalamus. It is separated from thalamus by, external medullary lamina. It receives information from, reticular formation, cerebral cortex and other thalamic, and sends inhibitory signals to other thalamic nuclei., PHYSIOLOGICAL CLASSIFICATION, On the basis of functions and their projections, thalamic, nuclei are classified into five groups. This type of, classification is also called Bondok classification. Five, groups of thalamic nuclei are:, 1. Specific sensory relay nuclei, 2. Specific motor nuclei, 3. Association or less specific nuclei, 4. Non-specific nuclei, 5. Limbic system nuclei., Nuclei and their functions of each group are given, in Table 147.1., , FIGURE 147.1: Thalamic nucleus. Red = Midline nucleus, Yellow = Intralaminar nuclei, Green = Medial mass of nuclei,, Blue = Lateral mass of nuclei, Pink = Posterior group of nuclei.
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Chapter 147 t Thalamus 849, TABLE 147.1: Bondok classification of thalamic nuclei, Group, , Nuclei, , Functions, , i. Ventral posterior nucleus, ii. Medical geniculate body, iii. Lateral geniculate body, , Project sensory signals to distinct (specific) areas, of cerebral cortex, , 2. Specific nuclei, , i. Ventral anterior nucleus, ii. Ventral lateral nucleus, , Receive signals controlling motor activities from, cerebellum and corpus striatum and send these, signals to motor areas in the cerebral cortex to, complete the feedback system of motor control, mechanism, , 3. Association or less specific nuclei, , i. Dorsolateral nucleus, ii. Posterolateral nucleus, iii. Pulvinar, , Send information to association areas of cerebral, cortex, , 4. Non-specific nuclei, , i. Midline nuclei, ii. Intralaminar nuclei, iii. Reticular nucleus, , Project signals to diffused areas of cerebral cortex, , 5. Limbic system nuclei, , i. Anterior nucleus, ii. Dorsolateral nucleus, , Project into limbic cortex, , 1. Specific sensory relay nuclei, , FIGURE 147.2: Connections of thalamus, , CONNECTIONS OF THALAMIC NUCLEI, Connections of different groups of nuclei are given in, Table 147.2 and Figure 147.2., , THALAMIC RADIATIONS, Thalamic radiation is the collection of nerve fibers, connecting thalamus and cerebral cortex. It contains, both thalamocortical and corticothalamic fibers. All, , these fibers between thalamus and cerebral cortex pass, through internal capsule., Fibers of thalamic radiation are divided into four, groups, which are called thalamic peduncles or thalamic, stalks. Thalamic peduncles are:, 1. Anterior (frontal) thalamic peduncle or radiation, 2. Superior (centroparietal) thalamic peduncle or, radiation, 3. Posterior (occipital) thalamic peduncle or radiation, 4. Inferior (temporal) thalamic peduncle or radiation.
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850 Section 10 t Nervous System, TABLE 147.2: Connections of different nuclear groups of thalamus, Nuclei, , Afferent fibers from, , Efferent fibers to, , 1. Midline nuclei, , Globus pallidus, Hypothalamus, Cerebral cortex, Midbrain nuclei, Reticular formation, , Different areas of cerebral cortex, , 2. Intralaminar nuclei, , Reticular formation, Trigeminal lemniscus, Lateral lemniscus, , Cerebral cortex, Putamen, Caudate nucleus, Other thalamic nuclei, , Mamillary body, , Limbic cortex, , Dorsomedial nucleus, , Hypothalamus, , Limbic cortex, Putamen, Caudate nucleus, Hypothalamus, , Dorsolateral nucleus, , Precuneus cortex, , Precuneus cortex, , Posterolateral nucleus, , Parietal lobe, , Parietal lobe, , Ventral anterior nucleus, , Globus pallidus, , Putamen, Caudate nucleus, Premotor cortex, , Ventral lateral nucleus, , Globus pallidus, Dentate nucleus, Red nucleus, , Putamen, Caudate nucleus, Precentral cortex, , Posterior ventral nucleus, , Trigeminal lemniscus, Medial lemniscus, Spinal lemniscus, , Hypothalamus, Cerebral cortex – areas 3, 1, 2, 5, 7, , Pulvinar, , Inferior parietal lobe, Occipital lobe – areas 18, 19, , Inferior parietal lobe, Occipital lobe – areas 18, 19, , Medial geniculate body, , Auditory tract, , Auditory cortex, , Lateral geniculate body, , Optic tract, , Visual cortex, , Anterior nucleus, 3. Medial mass, , 4. Lateral mass, , 5. Posterior group, , ANTERIOR (FRONTAL) THALAMIC, PEDUNCLE OR RADIATION, , POSTERIOR (OCCIPITAL), THALAMIC PEDUNCLE OR RADIATION, , Anterior thalamic peduncle connects the frontal lobe of, cerebral cortex with medial and lateral thalamic nuclei., It contains mostly motor nerve fibers., , Posterior thalamic peduncle connects occipital lobe of, cerebral cortex with pulvinar and lateral geniculate body., It contains the nerve fibers concerned with vision., , SUPERIOR (CENTROPARIETAL), THALAMIC PEDUNCLE OR RADIATION, , INFERIOR (TEMPORAL), THALAMIC PEDUNCLE OR RADIATION, , Fibers of this peduncle connect postcentral gyrus, (somesthetic area) of parietal lobe and adjacent area, in frontal cortex with lateral mass of thalamic nuclei. It, contains mainly the sensory fibers., , Fibers of this peduncle connect temporal lobe and insula, with pulvinar and medial geniculate body. This peduncle, contains the nerve fibers concerned with hearing.
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Chapter 147 t Thalamus 851, , FUNCTIONS OF THALAMUS, , 4. CENTER FOR SEXUAL SENSATIONS, , Thalamus is primarily concerned with somatic functions, and it plays little role in the visceral functions. Following, are the various functions of thalamus:, , Thalamus forms the center for perception of sexual, sensations., , 1. RELAY CENTER, Thalamus forms the relay center for the sensations., Impulses of almost all the sensations reach the, thalamic nuclei, particularly in the ventral posterolateral, nucleus. After being processed in the thalamus,, the impulses are carried to cerebral cortex through, thalamocortical fibers., 2. CENTER FOR PROCESSING, OF SENSORY INFORMATION, Thalamus forms the major center for processing, the sensory information. All the peripheral sensory, impulses reaching thalamus are integrated and, modified before being sent to specific areas of cerebral cortex. This function of thalamus is usually called, the processing of sensory information., , 5. ROLE IN AROUSAL AND, ALERTNESS REACTIONS, Because of its connections with nuclei of reticular, formation, thalamus plays an important role in arousal, and alertness reactions., 6. CENTER FOR REFLEX ACTIVITY, Since the sensory fibers relay here, thalamus forms the, center for many reflex activities., 7. CENTER FOR INTEGRATION, OF MOTOR ACTIVITY, Through the connections with cerebellum and basal, ganglia, thalamus serves as a center for integration of, motor functions., , APPLIED PHYSIOLOGY, , Functional Gateway for Cerebral Cortex, , THALAMIC LESION, , Almost all the sensations are processed in thalamus, before reaching cerebral cortex. Very little information, of somatosensory function is sent directly to cerebral, cortex without being processed by the thalamic nuclei., Because of this function, thalamus is usually called, ‘functional gateway’ for cerebral cortex., , Thalamic lesion occurs mainly because of blockage, (due to thrombosis) in thalamogeniculate branch of, posterior cerebral artery. Mostly, posteroventral nuclei, of thalamus are affected because the thalamogeniculate branch of posterior cerebral artery supplies, this part of thalamus. Lesion of thalamus leads to a, condition called thalamic syndrome., , 3. CENTER FOR DETERMINING, QUALITY OF SENSATIONS, Thalamus is also the center for determining the quality, of sensations, i.e. to determine the affective nature of, sensations. Usually the sensations have two qualities:, i. Discriminative nature, ii. Affective nature., , THALAMIC SYNDROME, Thalamic syndrome is the neurological disease caused, by infarction of posteroventral part of thalamus. It is, a rare disease and it has many names. Synonyms of, thalamic syndrome are listed in Box 147.1., BOX 147.1: Synonyms of thalamic syndrome, , i. Discriminative Nature, Discriminative nature is the ability to recognize the type,, location and other details of the sensations and it is the, function of cerebral cortex., ii. Affective Nature, Affective nature is the capacity to determine whether, a sensation is pleasant or unpleasant and agreeable, or disagreeable. Determining the affective nature of, sensations is the function of thalamus., , 1., 2., 3., 4., 5., 6., 7., , Dejerine-Roussy syndrome, Thalamic hyperesthetic anesthesia, Thalamic pain syndrome, Central pain syndrome, Central poststroke pain syndrome, Posterior thalamic syndrome, Retrolenticular syndrome, , In thalamic syndrome, whole body becomes hypersensitive to pain. Effects of thalamic lesion occur in the, contralateral (opposite) side.
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852 Section 10 t Nervous System, Following are the symptoms of thalamic syndrome:, 1. Loss of Sensations, Loss of all sensations (anesthesia) occurs as the, sensory relay system in thalamus is affected., 2. Astereognosis, Astereognosis is the loss of ability to recognize a, known object by touch with closed eyes. It is due to the, loss of tactile and kinesthetic sensations in thalamic, syndrome., 3. Ataxia, Ataxia refers to incoordination of voluntary movements. It occurs due to loss of kinesthetic sensation. This, type of ataxia due to loss of sensation is called sensory, ataxia. It is very common in thalamic syndrome., , Pain may be so intense, that it even resists the action, of powerful sedatives like morphine. Threshold for, pain is very much reduced. Even the light touch may, be unpleasant. Sometimes, the patient feels pain, even in the absence of pain stimulus. It becomes, worst in conditions such as emotional disturbance and, exposure to cold or heat. Pain is due to over activity, of medial mass of nuclei of thalamus, which escape, the lesion., Abnormal reaction to various stimuli is called, thalamic over-reaction., 7. Involuntary Movements, Thalamic syndrome is always associated with some, involuntary motor movements., Athetosis, Athetosis means slow writhing and twisting movements., , 4. Thalamic Phantom Limb, , Chorea, , The patient is unable to locate the position of a limb, with closed eyes. The patient may search for the limb, in air or may have the illusion that the limb is lost. This, is called thalamic phantom limb., , Chorea means quick, jerky, involuntary movements., , 5. Anosognosia, Anosognosia is the lack of awareness or denial of, existance of a neurological defect or general illness or, any disability., 6. Spontaneous Pain and, Thalamic Over-reaction, Spontaneous pain occurs often. Pain stimulus is felt, more acutely than in normal conditions (hyperalgesia)., , Intention tremor, Tremor is defined as rapid alternate rhythmic and, involuntary movement of flexion and extension in the, joints of fingers and wrist or elbow. Intention tremor is, the tremor that develops while attempting to do any, voluntary act. Intention tremor is the common feature of, thalamic syndrome., 8. Thalamic Hand or Athetoid Hand, Athetoid hand is the abnormal attitude of hand in, thalamic lesion. It is characterized by moderate flexion, at wrist and hyperextension of all fingers.
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Chapter, , Internal Capsule, , 148, , DEFINITION, SITUATION, DIVISIONS, , , , , , ANTERIOR LIMB, POSTERIOR LIMB, GENU, CAUDAL PORTION, , APPLIED PHYSIOLOGY – EFFECT OF LESIONS, , , , , , IN ANTERIOR LIMB, IN POSTERIOR LIMB, IN GENU, IN CAUDAL PORTION, , DEFINITION, Internal capsule is the broad and compact band of, afferent and efferent fibers connecting cerebral cortex, with brainstem and spinal cord. Cerebral cortex is, connected with brainstem and spinal cord by both, afferent and efferent fibers. Fibers arising from, different parts of cerebral cortex descend down into, white matter of cerebral hemispheres in the form of, radiating mass of fibers called corona radiata. While, passing down towards the brainstem, corona radiata, converges in the form of internal capsule., Fibers from spinal cord and brainstem reach, cerebral cortex in the same route. A large portion of, internal capsule is formed by thalamic radiation., , SITUATION, Internal capsule is situated in between thalamus and, caudate nucleus on the medial side and lenticular, nucleus on the lateral side., , DIVISIONS, Internal capsule has two limbs, the anterior and post, erior limbs. In between these two limbs, lies the genu of, internal capsule. Distal end of posterior limb is continued, , as the caudal portion of internal capsule (Fig. 148.1)., Nerve fibers of each division are given in Table 148.1., ANTERIOR LIMB, Anterior limb of internal capsule is short and lies, between lenticular and caudate nuclei., POSTERIOR LIMB, Posterior limb is long and situated between thalamus, and lenticular nucleus., GENU, Genu is situated between the anterior and the posterior, limbs., CAUDAL PORTION, Caudal portion is otherwise known as retrolenticular, portion of internal capsule., , APPLIED PHYSIOLOGY – EFFECT OF, LESIONS OF INTERNAL CAPSULE, Lesion of internal capsule is caused by thrombosis or, hemorrhage in branches of middle cerebral arteries.
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854 Section 10 t Nervous System, , FIGURE 148.1: Components of internal capsule. Pink = Descending fibers, Blue = Ascending fibers., , The effects of lesion depend upon the part of internal, capsule involved., TABLE 148.1: Fibers of internal capsule, Nerve fibers present, , Division, , 1. Anterior limb, , 1. Anterior thalamic radiation, 2. Prefrontal corticopontine, (frontopontine) tract, 3. Fibers from orbital cortex to, hypothalamus, , 2. Posterior limb, , 1. Corticospinal tracts, 2. Superior thalamic radiation, 3. Frontal corticopontine tract, , 3. Genu, , Corticobulbar tract, , 4. Caudal portion, , Posterior thalamic radiation, , IN POSTERIOR LIMB, Lesion in posterior limb affects the sensory fibers, (thalamocortical fibers). So, it causes:, 1. Contralateral hemianesthesia (loss of sen, sation in opposite side of the body), 2. Contralateral hemihyperesthesia (abnormal, sensation in opposite side of the body), 3. Hemiplegia (paralysis of upper and lower, limbs in one side of the body)., Hemianesthesia and hemiparesthesia occur, because of lesion of superior thalamic radiation., Hemiplegia is due to injury of corticospinal tracts., IN GENU, Lesion in genu causes alteration in motor activities in, opposite side due to damage of corticobulbar fibers., IN CAUDAL PORTION, , IN ANTERIOR LIMB, Anterior limb contains thalamocortical and frontopontine, fibers. Lesion in this limb causes widespread disability, in the body. Both motor and sensory functions are lost., , Lesion in this portion of internal capsule causes, contralateral hemianesthesia. It also produces, hemianopia and deafness, because of the involve, ment of the auditory and visual fibers.
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Chapter, , Hypothalamus, , 149, , INTRODUCTION, NUCLEI, CONNECTIONS, , , , AFFERENT CONNECTIONS, EFFERENT CONNECTIONS, , FUNCTIONS, , , , , , , , , , , , , , , , , SECRETION OF POSTERIOR PITUITARY HORMONES, CONTROL OF ANTERIOR PITUITARY, CONTROL OF ADRENAL CORTEX, CONTROL OF ADRENAL MEDULLA, REGULATION OF AUTONOMIC NERVOUS SYSTEM, REGULATION OF HEART RATE, REGULATION OF BLOOD PRESSURE, REGULATION OF BODY TEMPERATURE, REGULATION OF HUNGER AND FOOD INTAKE, REGULATION OF WATER BALANCE, REGULATION OF SLEEP AND WAKEFULNESS, ROLE IN BEHAVIOR AND EMOTIONAL CHANGES, REGULATION OF SEXUAL FUNCTION, ROLE IN RESPONSE TO SMELL, ROLE IN CIRCADIAN RHYTHM, , APPLIED PHYSIOLOGY – DISORDERS, , , , , , , , DIABETES INSIPIDUS, DYSTROPHIA ADIPOSOGENITALIS, KALLMANN SYNDROME, LAURENCE-MOON-BIEDL SYNDROME, NARCOLEPSY, CATAPLEXY, , INTRODUCTION, , NUCLEI OF HYPOTHALAMUS, , Hypothalamus is a diencephalic structure. It is situated, just below thalamus in the ventral part of diencephalon., It is formed by groups of nuclei, scattered in the walls, and floor of third ventricle. It extends from optic chiasma, to mamillary body., , Nuclei of hypothalamus are divided into three groups:, 1. Anterior or preoptic group, 2. Middle or tuberal group, 3. Posterior or mamillary group., Nuclei of each group are listed in Table 149.1 and, represented diagrammatically in Figure 149.1.
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Chapter 149 t Hypothalamus 857, , FUNCTIONS OF HYPOTHALAMUS, Hypothalamus is the important part of brain, concerned, with homeostasis of the body. It regulates many vital, functions of the body like endocrine functions, visceral, functions, metabolic activities, hunger, thirst, sleep, wakefulness, emotion, sexual functions, etc. (Table 149.2)., 1. SECRETION OF POSTERIOR, PITUITARY HORMONES, Hypothalamus is the site of secretion for the posterior, pituitary hormones. Antidiuretic hormone (ADH) and, oxytocin are secreted by supraoptic and paraventricular, nuclei. These two hormones are transported by means, of axonic or axoplasmic flow through the fibers of hypo, thalamohypophyseal tracts to posterior pituitary. Refer, Chapter 66 for details., 2. CONTROL OF ANTERIOR PITUITARY, Hypothalamus controls the secretions of anterior pituitary, gland by secreting releasing hormones and inhibitory, hormones. It secretes seven hormones., i. Growth hormone-releasing hormone (GHRH), ii. Growth hormone-releasing polypeptide (GHRP), iii. Growth hormone-inhibiting hormone (GHIH) or, somatostatin, iv. Thyrotropin-releasing hormone (TRH), v. Corticotropin-releasing hormone (CRH), vi. Gonadotropin-releasing hormone (GnRH), vii. Prolactin-inhibiting hormone (PIH)., , These hormones are secreted by discrete areas of, hypothalamus and transported to anterior pituitary by, the hypothalamohypophyseal portal blood vessels., Refer Chapter 66 for details., 3. CONTROL OF ADRENAL CORTEX, Anterior pituitary regulates adrenal cortex by secreting, adrenocorticotropic hormone (ACTH). ACTH secretion, is in turn regulated by corticotropin-releasing hormone, (CRH), which is secreted by the paraventricular nucleus, of hypothalamus (Refer Chapter 70 for details)., 4. CONTROL OF ADRENAL MEDULLA, Dorsomedial and posterior hypothamic nuclei are, excited by emotional stimuli. These hypothalamic, nuclei, in turn, send impulses to adrenal medulla, through sympathetic fibers and cause release of, catecholamines, which are essential to cope up with, emotional stress (Chapter 71)., 5. REGULATION OF AUTONOMIC, NERVOUS SYSTEM, Hypothalamus controls autonomic nervous system, (ANS). Sympathetic division of ANS is regulated, by posterior and lateral nuclei of hypothalamus., Parasympathetic division of ANS is controlled by anterior, group of nuclei. The effects of cerebral cortex on ANS, are executed through hypothalamus (Chapter 164)., , FIGURE 149.2: Connections of hypothalamus
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858 Section 10 t Nervous System, TABLE 149.2: Functions of hypothalamus, Functions, , Action/Center, , Nuclei/Parts involved, , 1. Control of anterior pituitary, , Releasing hormones, Inhibiting hormones, , Discrete areas, , 2. Secretion of posterior pituitary hormones, , Oxytocin, Antidiuretic hormone (ADH), , Paraventricular nucleus, Supraoptic nucleus, , 3. Control of adrenal cortex, , Corticotropin-releasing hormone (CRH), , Paraventricular nucleus, , 4. Control of adrenal medulla, , Catecholamines during emotion, , Posterior and dorsomedial nuclei, , 5. Regulation of autonomic nervous system, (ANS), , Sympathetic, Parasympathetic, , Posterior and lateral nuclei, Anterior nuclei, , 6. Regulation of heart rate, , Acceleration, Inhibition, , Posterior and lateral nuclei, Preoptic and anterior nuclei, , 7. Regulation of blood pressure, , Pressor effect, Depressor effect, , Posterior and lateral nuclei, Preoptic area, , 8. Regulation of body temperature, , Heat gain center, Heat loss center, , Posterior hypothalamus, Anterior hypothalamus, , 9. Regulation of hunger and food intake, , Feeding center, Satiety center, , Lateral nucleus, Ventromedial nucleus, , 10. Regulation of water intake, , Thirst center, Water retention by ADH, , Lateral nucleus, Supraoptic nucleus, , 11. Regulation of sleep and wakefulness, , Sleep, Wakefulness, , Anterior hypothalamus, Mamillary body, , 12. Regulation of behavior and emotion, , Reward center, Punishment center, , Ventromedial nucleus, Posterior and lateral nuclei, , 13. Regulation of sexual function, , Sexual cycle, , Arcuate and posterior nuclei, , 14. Regulation of response to smell, , Autonomic responses, , Posterior hypothalamus, , 15. Role in circadian rhythm, , Rhythmic changes, , Suprachiasmatic nucleus, , 6. REGULATION OF HEART RATE, Hypothalamus regulates heart rate through vasomotor, center in the medulla oblongata. Stimulation of posterior, and lateral nuclei of hypothalamus increases the, heart rate. Stimulation of preoptic and anterior nuclei, decreases the heart rate (Chapter 101)., 7. REGULATION OF BLOOD PRESSURE, Hypothalamus regulates the blood pressure by acting, on the vasomotor center. Stimulation of posterior and, lateral hypothalamic nuclei increases arterial blood, pressure and stimulation of preoptic area decreases, the blood pressure (Chapter 103)., , Hypothalamus has two centers which regulate the body, temperature:, i. Heat loss center that is present in preoptic, nucleus of anterior hypothalamus, ii. Heat gain center that is situated in posterior, hypothalamic nucleus., Regulation of body temperature is explained in, Chapter 63., 9. REGULATION OF HUNGER AND, FOOD INTAKE, Food intake is regulated by two centers present in, hypothalamus:, i. Feeding center, ii. Satiety center., , 8. REGULATION OF BODY TEMPERATURE, Body temperature is regulated by hypothalamus, which, sets the normal range of body temperature. The set, point, under normal physiological conditions is 37°C., , Feeding Center, Feeding center is in the lateral hypothalamic nucleus., In experimental conditions, stimulation of this center
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Chapter 149 t Hypothalamus 859, in animals leads to uncontrolled hunger and increased, food intake (hyperphagia), resulting in obesity., Destruction of feeding center leads to loss of appetite, (anorexia) and the animal refuses to take food., Normally, feeding center is always active. That means,, it has the tendency to induce food intake always., Satiety Center, Satiety center is in the ventromedial nucleus of, the hypothalamus. Stimulation of this nucleus in, animals causes total loss of appetite and cessation, of food intake. Destruction of satiety center leads to, hyperphagia and the animal becomes obese. This, type of obesity is called hypothalamic obesity., Satiety center plays an important role in the regulation of food intake by temporary inhibition of feeding, center after food intake., , While taking food, blood glucose level increases., Slowly the glucostats are stimulated and satiety center, is activated. At one stage, it develops the feeling of, ‘fullness’. Now, the satiety center inhibits the feeding, center and stops the food intake., After few hours of food intake, the blood glucose, level decreases and satiety center becomes inactive., So, the feeding center is no longer inhibited. Now it, becomes active and increases the appetite and induces, food intake. After taking food, once again blood glucose, level increases and the cycle is repeated (Fig. 149.3)., However, glucostats do not give response to, very high level of glucose in blood (hyperglycemia)., So, in conditions like diabetes, hyperglycemia fails to, stimulate the satiety center. The satiety center does, not inhibit the feeding center, so the frequency of food, intake increases (polyphagia)., , Mechanism of Regulation of Food Intake, Under normal physiological conditions, appetite and, food intake are well balanced and continues in a, cyclic manner. Feeding center and satiety center of, hypothalamus are responsible for the regulation of, appetite and food intake. These centers are regulated, by the following mechanisms:, i. Glucostatic mechanism, ii. Lipostatic mechanism, iii. Peptide mechanism, iv. Hormonal mechanism, v. Thermostatic mechanism., i. Glucostatic Mechanism, Cells of satiety center function as glucostats or glucose, receptors, which are stimulated by increased blood, glucose level., , ii. Lipostatic Mechanism, Leptin is a peptide secreted by adipocytes (cells of, , adipose tissue). It plays an important role in controlling, the food intake and adipose tissue volume. Details of, leptin are given in Chapter 73., When the volume of adipose tissues increases,, adipocytes secrete and release a large quantity of, leptin into the blood. While circulating through brain,, leptin crosses the blood-brain barrier and enters, hypothalamus., In hypothalamus, leptin inhibits the feeding center,, resulting in loss of appetite and stoppage of food, intake. It is suggested that the cells present in bloodbrain barrier contain many receptor-like proteins, which, are responsible for the transport of leptin across the, barrier., , FIGURE 149.3: Glucostatic mechanism
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860 Section 10 t Nervous System, Mode of action of leptin, Leptin acts through some specific neuropeptides in, hypothalamus, such as:, a. Neuropeptide Y: It is secreted in small intestine,, medulla and hypothalamus. Normally, this peptide, stimulates the food intake. But, leptin inhibits, neuropeptide Y, leading to stoppage of food intake. Refer Chapters 44 and 141 for details of, neuropeptide Y., b. Pro-opiomelanocortin (POMC): It is secreted, from anterior pituitary. It is also secreted from, hypothalamus, lungs, GI tract and placenta., Normally, it inhibits food intake. Leptin stimulates, the secretion of POMC., Leptin receptor, Many leptin receptors are identified. However, leptin acts, via ‘LepRb’, which is the only active receptor present in, many nuclei of hypothalamus., iii. Peptide Mechanism, Some peptides regulate the food intake either by, stimulating or inhibiting the feeding center, directly or, indirectly. The important one among the peptides is, ghrelin., Ghrelin is secreted in stomach (Chapter 44) during, fasting. It directly stimulates the feeding center and, increases the appetite and food intake. Besides ghrelin,, several other peptides are involved in the regulation of, food intake., Peptides, which increase the food intake:, a. Ghrelin, b. Neuropeptide Y., Peptides, which decrease the food intake:, a. Leptin, b. Peptide YY., iv. Hormonal Mechanism, Some endocrine hormones and GI hormones inhibit, the food intake by acting through hypothalamus., Hormones which inhibit the food intake:, a. Somatostatin, b. Oxytocin, c. Glucagon, d. Pancreatic polypeptide, e. Cholecystokinin., v. Thermostatic Mechanism, Food intake is inversely proportional to body temperature. So in fever, the food intake is decreased. Exact, , mechanism of this fact is not known. It is suggested, that the preoptic thermoreceptors (see above) may act, via feeding center. The cytokines are also suggested to, play a role in decreasing the appetite during fever., 10. REGULATION OF WATER BALANCE, Hypothalamus regulates water content of the body by, two mechanisms:, i. Thirst mechanism, ii. Antidiuretic hormone (ADH) mechanism., i. Thirst Mechanism, Thirst center is in the lateral nucleus of hypothalamus., There are some osmoreceptors in the areas adjacent, to thirst center. When the ECF volume decreases, the, osmolality of ECF is increased. If the osmolarity increases, by 1% to 2%, the osmoreceptors are stimulated. Osmoreceptors in turn, activate the thirst center and thirst, sensation is initiated. Now, the person feels thirsty and, drinks water. Water intake increases the ECF volume, and decreases the osmolality (Fig. 149.4)., ii. ADH Mechanism, Simultaneously, when the volume of ECF decreases, with increased osmolality, the supraoptic nucleus is, stimulated and ADH is released. ADH causes retention, of water by facultative reabsorption in the renal tubules., It increases the ECF volume and brings the osmolality, back to the normal level. On the contrary, when ECF, volume is increased, the supraoptic nucleus is not, stimulated and ADH is not secreted. In the absence of, ADH, more amount of water is excreted through urine, and the volume of ECF is brought back to normal., 11. REGULATION OF SLEEP, AND WAKEFULNESS, Mamillary body in the posterior hypothalamus is, considered as the wakefulness center. Stimulation, of mamillary body causes wakefulness and its lesion, leads to sleep. Stimulation of anterior hypothalamus, also leads to sleep., 12. ROLE IN BEHAVIOR AND, EMOTIONAL CHANGES, The behavior of animals and human beings is mostly, affected by two responding systems in hypothalamus, and other structures of limbic system. These two, systems act opposite to one another., The responding systems are concerned with the, affective nature of sensations, i.e. whether the sensations
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Chapter 149 t Hypothalamus 861, Role of Reward and Punishment Centers, The importance of the reward and punishment centers, lies in the behavioral pattern of the individuals. Almost, all the activities of day-to-day life depend upon reward, and punishment. While doing something, if the person, is rewarded or feels satisfied, he or she continues to, do so. If the person feels punished or unpleasant, he, or she stops doing so. Thus, these two centers play, an important role in the development of the behavioral, pattern of a person., Rage, Rage refers to violent and aggressive emotional, expression with extreme anger. It can be developed, in animals by stimulating the punishment centers in, posterior and lateral hypothalamus. The reactions of, rage are expressed by developing a defense posture,, which includes:, i. Extension of limbs, ii. Lifting of tail, iii. Hissing and spitting, iv. Piloerection, v. Wide opening of eyeballs, vi. Dilatation of pupil, vii. Severe savage attack even by mild provocation., Sham Rage, , FIGURE 149.4: Thirst mechanism. ECF = Extracellular fluid., , are pleasant or painful. These two qualities are called, the reward (satisfaction) and punishment (aversion or, avoidance). Hypothalamus has two centers for behaviorial and emotional changes. They are:, i. Reward center, ii. Punishment center., Reward Center, Reward center is situated in medial forebrain bundle, and ventromedial nucleus of hypothalamus. Electrical, stimulation of these areas in animals pleases or satisfies, the animals., Punishment Center, Punishment center is situated in posterior and lateral, nuclei of hypothalamus. Electrical stimulation of these, nuclei in animals leads to pain, fear, defense, escape, reactions and other elements of punishment., , Sham rage means false rage. It is an extreme emotional, condition that resembles rage and occurs in some, pathological conditions in humans., In physiological conditions, the animals and human, beings maintain a balance between the rage and its, opposite state. This balanced condition is called the calm, emotional state. A major irritation may make a person, to loose the temper. However, the minor irritations are, usually ignored or overcome. It is because of inhibitory, influence of cerebral cortex on hypothalamus. But the, calm emotional state is altered during brain lesions. In, some cases, even a mild stimulus evokes sham rage. It, can occur in decorticated animal also., Sham rage is due to release of hypothalamus from, the inhibitory influence of cortical control., 13. REGULATION OF SEXUAL FUNCTION, In animals, hypothalamus plays an important role, in maintaining the sexual functions, especially in, females. A decorticate female animal will have regular, estrous cycle, provided the hypothalamus is intact., In human beings also, hypothalamus regulates the, sexual functions by secreting gonadotropinreleasing
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862 Section 10 t Nervous System, hormones. Arcuate and posterior hypothalamic nuclei, are involved in the regulation of sexual functions., 14. ROLE IN RESPONSE TO SMELL, Posterior hypothalamus along with other structures like, hippocampus and brainstem nuclei are responsible for, the autonomic responses of body to olfactory stimuli., The responses include feeding activities and emotional, responses like fear, excitement and pleasure., 15. ROLE IN CIRCADIAN RHYTHM, Circadian rhythm is the regular recurrence of physiological processes or activities, which occur in cycles of, 24 hours. It is also called diurnal rhythm. The term, circadian is a Latin word, meaning ‘around the day’., Circadian rhythm develops in response to recurring, daylight and darkness. The cyclic changes taking place, in various physiological processes are set by means, of a hypothetical internal clock that is often called, biological clock., , Suprachiasmatic nucleus of hypothalamus plays, an important role in setting the biological clock by its, connection with retina via retinohypothalamic fibers., Through the efferent fibers, it sends circadian signals, to different parts and maintains the circadian rhythm of, sleep, hormonal secretion, thirst, hunger, appetite, etc., Whenever body is exposed to a new pattern of, daylight or darkness rhythm, the biological clock is, reset, provided the new pattern is regular. Accordingly,, the circadian rhythm also changes., , APPLIED PHYSIOLOGY –, DISORDERS OF HYPOTHALAMUS, The lesion of hypothalamus occurs due to tumors,, encephalitis and ischemia. Following features develop, in hypothalamic lesion:, 1. Disturbances in carbohydrate and fat metabolisms,, when lateral, arcuate and ventromedial nuclei are, involved in lesion, 2. Disturbance in sleep due to lesion in mamillary body, and anterior hypothalamus, 3. Disturbance in sympathetic or parasympathetic, function occurs due to lesion in posterior, lateral and, anterior nuclei, 4. Emotional manifestations, leading to sham rage due, to lesion in ventromedial and posterolateral parts, 5. Disturbance in sexual functions due to the lesion in, midhypothalamus., One or more of the above features can become, prominent, resulting in some clinical manifestations, such as:, 1. Diabetes insipidus, 2. Dystrophia adiposogenitalis, , 3., 4., 5., 6., , Kallmann syndrome, Laurence-Moon-Biedl syndrome, Narcolepsy, Cataplexy., , DIABETES INSIPIDUS, Diabetes insipidus is the condition characterized by, excretion of large quantity of water through urine. Refer, Chapter 66 for details., DYSTROPHIA ADIPOSOGENITALIS, This condition is characterized by obesity and sexual, infantilism, associated with dwarfism (if the condition, occurs during growing period). It is also called Fröhlich, syndrome. Refer Chapter 66 for details., KALLMANN SYNDROME, Kallmann syndrome is a genetic disorder characterized, by hypogonadism, associated with anosmia (loss of, olfactory sensation) or hyposmia (decreased olfactory sensation). It is also called hypogonadotropic, hypogonadism, since it occurs due to deficiency of, gonadotropin-releasing hormones, secreted by hypothalamus. Refer Chapter 66 for details., LAURENCE-MOON-BIEDL SYNDROME, This disorder of hypothalamus is characterized by, moon face (facial contours become round by hiding the, bony structures), obesity, polydactylism (having one, or more extra fingers or toes), mental retardation and, hypogenitalism., NARCOLEPSY, Narcolepsy is a hypothalamic disorder with abnormal, sleep pattern. There is a sudden attack of uncontrollable, desire for sleep and the person suddenly falls asleep. It, occurs in the daytime., The sleep may resemble the normal sleep. The, duration of sleep is very short. It may be from few, seconds to 20 minutes. In night, sleep may be normal, but is often disturbed or there may be insomnia (loss, of sleep)., CATAPLEXY, Cataplexy is the sudden uncontrolled outbursts of, emotion associated with narcolepsy. Due to emotional, outburst like anger, fear or excitement, the person, becomes completely exhausted with muscular weak, ness. The attack is brief and last for few seconds to a, few minutes. Consciousness is not lost.
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Chapter, , Cerebellum, , 150, , PARTS, , , , VERMIS, CEREBELLAR HEMISPHERES, , DIVISIONS, , , , , ANATOMICAL DIVISIONS, PHYLOGENETIC DIVISIONS, FUNCTIONAL DIVISIONS, , FUNCTIONAL ANATOMY, , , , , GRAY MATTER, CEREBELLAR NUCLEI, WHITE MATTER, , VESTIBULOCEREBELLUM, , , , , COMPONENTS, CONNECTIONS, FUNCTIONS, , SPINOCEREBELLUM, , , , , COMPONENTS, CONNECTIONS, FUNCTIONS, , CORTICOCEREBELLUM, , , , , , COMPONENTS, CONNECTIONS, AFFERENT-EFFERENT CIRCUIT, FUNCTIONS, , APPLIED PHYSIOLOGY – CEREBELLAR LESIONS, , , , , DISTURBANCES IN TONE AND POSTURE, DISTURBANCES IN EQUILIBRIUM, DISTURBANCES IN MOVEMENTS, , PARTS OF CEREBELLUM, Cerebellum consists of a narrow, worm-like central body, called vermis and two lateral lobes, the right and left, cerebellar hemispheres (Fig. 150.1)., VERMIS, Vermis of cerebellum is formed by nine parts. Part of, vermis on the upper surface of cerebellum is known, , as superior vermis and the part on lower surface of, cerebellum is called inferior vermis., Parts of superior vermis and inferior vermis are, listed in Table 150.1., Nodulus is continued on either side as an, elongated and somewhat lobulated structure called, flocculus. Nodulus and flocculi are together called, flocculonodular lobe. On either side of pyramid, there, is another extension named paraflocculus.
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864 Section 10 t Nervous System, , FIGURE 150.1: Parts and functional divisions of cerebellum, , TABLE 150.1: Parts of superior and inferior vermis, Superior vermis, 1., 2., 3., 4., 5., , Lingula, Central lobe, Culmen, Lobulus simplex, Declive, , Inferior vermis, 6., 7., 8., 9., , Tuber, Pyramid, Uvula, Nodulus, , Fissures Present Over the Surface of Vermis, 1. Primary fissure between culmen and lobulus simplex, 2. Prepyramidal fissure between tuber and pyramid, 3. Posterolateral fissure between uvula and nodulus., CEREBELLAR HEMISPHERES, Cerebellar hemispheres are the extended portions on, either side of vermis., Each hemisphere has two portions:, 1. Lobulus ansiformis or ansiform lobe, which is the, larger portion of cerebellar hemisphere, 2. Lobulus paramedianus or paramedian lobe, which, is the smaller portion of cerebellar hemisphere., , DIVISIONS OF CEREBELLUM, Division of cerebellum into different major parts is done, by three methods:, A. Anatomical divisions, B. Phylogenetic divisions, C. Physiological or functional divisions., , ANATOMICAL DIVISIONS, On structural basis, the whole cerebellum is divided into, three portions:, 1. Anterior lobe, 2. Posterior lobe, 3. Flocculonodular lobe., 1. Anterior Lobe, Anterior lobe includes lingula, central lobe and culmen., It is separated from posterior lobe by primary fissure., 2. Posterior Lobe, Posterior lobe consists of lobulus simplex, declive, tuber,, pyramid, uvula, paraflocculi and the two portions of, hemispheres, viz. ansiform lobe and paramedian lobe., 3. Flocculonodular Lobe, Flocculonodular lobe includes nodulus and the lateral, extension on either side called flocculus. It is separated, from rest of the cerebellum by posterolateral fissure., PHYLOGENETIC DIVISIONS, Depending upon phylogeny, the cerebellum is divided, into two divisions:, 1. Paleocerebellum, 2. Neocerebellum.
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Chapter 150 t Cerebellum 865, 1. Paleocerebellum, Paleocerebellum is the phylogenetically oldest part of, cerebellum. It includes two divisions:, i. Archicerebellum, which includes flocculonodular lobe, ii. Paleocerebellum proper, which includes lingula,, central lobe, culmen, lobulus simplex, pyramid,, uvula and paraflocculi., 2. Neocerebellum, Neocerebellum is the phylogenetically newer portion of, cerebellum. It includes declive, tuber and the two portions, of cerebellar hemispheres, viz. lobulus ansiformis and, lobulus paramedianus., PHYSIOLOGICAL OR, FUNCTIONAL DIVISIONS, Based on functions, the cerebellum is divided into three, divisions:, 1. Vestibulocerebellum, 2. Spinocerebellum, 3. Corticocerebellum., 1. Vestibulocerebellum, Vestibulocerebellum includes flocculonodular lobe that, forms the archicerebellum., 2. Spinocerebellum, Spinocerebellum includes lingula, central lobe, culmen,, lobulus simplex, declive, tuber, pyramid, uvula and, paraflocculi and medial portions of lobulus ansiformis, and lobulus paramedianus., 3. Corticocerebellum, Corticocerebellum includes lateral portions of lobulus, ansiformis and lobulus paramedianus., , FUNCTIONAL ANATOMY, OF CEREBELLUM, Cerebellum is made up of outer gray matter or, cerebellar cortex and an inner white matter. White, matter is formed by afferent and efferent nerve fibers of, cerebellum. Gray masses called cerebellar nuclei are, located within the white matter., GRAY MATTER, Gray matter or cerebellar cortex is made up of, structures arranged in three layers (Fig. 150.2)., , Each layer of gray matter is uniform in structure and, thickness, throughout the cerebellum., Layers of gray matter:, 1. Outer molecular or plexiform layer, 2. Intermediate Purkinje layer, 3. Inner granular layer., 1. Molecular or Plexiform Layer, Molecular or plexiform layer is the outermost layer of, cortex having the cells arranged in two strata. Superficial, stratum contains few star-shaped cells known as stellate, cells. Deep stratum contains basket cells. In addition to, stellate and basket cells, the molecular layer contains, the following structures:, i. Parallel fibers, which are the axons of granule, cells, present in granular layer, ii. Terminal portions of climbing fibers (afferents, from medulla), iii. Dendrites of Purkinje cells and Golgi cells., Cell junctions in molecular layer, Molecular layer contains the following cellular junctions:, i. Dendrites of stellate cells and basket cells, synapse with parallel fibers, which are the axons, of granule cells, ii. Axons of stellate cells end on the dendrites of, Purkinje cells. However, the axon of basket cell, descends down into the Purkinje layer and forms, the transverse fiber, that ends on the soma of, Purkinje cells., iii. Dendrites of Purkinje cells synapse with climbing, fibers and parallel fibers, iv. Dendrites of Golgi cells situated in inner granular, layer enter the molecular layer and end on, parallel fibers., 2. Purkinje Layer, Purkinje layer is situated in between outer molecular layer, and inner granular layer. It is the thinnest layer, having a, single layer of flask-shaped Purkinje cells. Purkinje cells, are the largest neurons in the body. Dendrites of these, cells ascend through the entire thickness of molecular, layer and arborize there. These dendrites terminate, either on climbing fibers or the parallel fibers. Axons, of the basket cells form the transverse fibers, which, descend down and end on the soma of Purkinje cells., Axons of Purkinje cells descend into the white matter, and terminate on the cerebellar nuclei and vestibular, nuclei via cerebellovestibular tract., Purkinje cells are termed as ‘final common path’, of cerebellar cortex. It is because the impulses from
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866 Section 10 t Nervous System, , FIGURE 150.2: Structure of cerebellar cortex. (+) = Excitation, (–) = Inhibition., , different parts of cerebellar cortex are transmitted to, other parts of brain only through Purkinje cells., 3. Granular Layer, Granular layer is the innermost layer of cerebellar, gray matter and it is in between Purkinje layer and the, cerebellar white matter. It is formed by interneurons, called granule cells and Golgi cells. Total number of, interneurons in this layer is about half the number of all, neurons in the whole nervous system., Axon of granule cell ascends into molecular layer and, forms the parallel fiber, which synapses with dendrites, of Purkinje cells, stellate cells, basket cells and Golgi, cells. Dendrites of granule cells and the axon and few, dendrites of a Golgi cell synapse with Mossy fiber. The, synaptic area of these cells is called glomerulus and it, is encapsulated by the processes of glial cells., Afferent Fibers to Cerebellar Cortex, Cerebellar cortex receives afferent signals from other, parts of brain through two types of nerve fibers:, , 1. Climbing fibers, 2. Mossy fibers., 1. Climbing fibers, Climbing fibers arise from the neurons of inferior, olivary nucleus, situated in medulla and reach the, cerebellum via olivocerebellar tract. Inferior olivary, nucleus relays the output signals from motor areas, of cerebral cortex and the proprioceptive signals from, different parts of the body to the cerebellar cortex via, climbing fibers. Proprioceptive impulses from different, parts of the body reach the inferior olivary nucleus, through spinal cord and vestibular system., After reaching the cerebellum, the climbing fibers, ascend into molecular layer and terminate on the, dendrites of Purkinje cells. While passing through, cerebellum, climbing fibers of olivocerebellar tract, send collaterals to cerebellar nuclei. So, impulses, from cerebral cortex and proprioceptors of the body, are conveyed not only to cerebellar cortex, but also to, the cerebellar nuclei through the climbing fibers. Each, climbing fiber innervates one single Purkinje cell.
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Chapter 150 t Cerebellum 867, 2. Mossy fibers, , aspartate. Excitatory effect of climbing fiber on, , Unlike climbing fibers, the mossy fibers have many, sources of origin, namely motor areas of cerebral, cortex, pons, medulla and spinal cord. Fibers arising, from all these areas send collaterals to cerebellar nuclei, before reaching the cerebellar cortex. So, like climbing, fibers, mossy fibers also convey afferent impulses to, both cerebellar nuclei and cerebellar cortex. Some of, the mossy fibers arise from cerebellar nuclei., Mossy fibers reach the granular layer of cerebellar, cortex and divide into many terminals. Each terminal, enters a specialized structure called glomerulus and, ends in a large expanded structure that forms the, central portion of the glomerulus. Dendrites of granule, cells and axon and dendrites of Golgi cells synapse, on the mossy fiber giving a thick bushy appearance., The word ‘mossy’ refers to the appearance of a plant, called moss, which grows into dense clumps and, hence, these fibers are called mossy fibers., , Purkinje cell is very strong because each climbing, fiber ends on a single Purkinje cell (Table 150.2)., Mossy fibers excite the Purkinje cells indirectly. In, the glomeruli, mossy fibers release glutamate and, excite the granule cells and Golgi cells. Collaterals, of mossy fibers activate the cerebellar nuclei also, by glutamate., Granule cells, which are activated by mossy fibers, in turn, excite the Purkinje cells, stellate cells and, the basket cells through the parallel fibers., Neurotransmitter utilized by granule cells is, glutamate or aspartate. Granule cells are the, only excitatory cells in cerebellar cortex, while all, other cells are inhibitory in function. Each mossy, fiber innervates many Purkinje cells indirectly via, granule cells. So, the excitatory effect of mossy, fibers on Purkinje cells is weak., Stellate cells and basket cells, which are activated, by granule cells, inhibit the Purkinje cells by, releasing GABA. This type of inhibition is called, feed forward inhibition (Chapter 140)., Golgi cell that is activated by mossy fibers, in turn,, provides feedback inhibition to granule cells by, releasing GABA, i.e. it inhibits the transmission of, impulse from mossy fiber to granule cell, Cerebellar nuclei are excited by collaterals from, climbing and mossy fibers. In turn, the nuclei send, excitatory impulses to thalamus and different nuclei, in brainstem., However, signals discharged from Purkinje cells, inhibit cerebellar nuclei via GABA. Purkinje cells, , 2., , 3., , 4., , Neuronal Activity in Cerebellar Cortex and Nuclei, Functions of cerebellum are executed mainly by the, impulses discharged from cerebellar nuclei. However,, cerebellar cortex controls the discharge from nuclei, constantly via the fibers of Purkinje cells. It is done, in accordance with the signals received by cerebellar, cortex from different parts of the brain and body via, climbing and mossy fibers., Entire process involves a series of neuronal, activity:, 1. Climbing fibers excite the Purkinje cells directly, and cerebellar nuclei via collaterals, by releasing, , 5., , 6., , 7., , TABLE 150.2: Interneuronal activity in cerebellum, Neuron, , Action on, , Action, , Neurotransmitter, , Climbing fibers, , Purkinje cells and, Cerebellar nuclei, , Excitation, , Aspartate, , Mossy fibers, , Granule cells, Golgi cells and, Cerebellar nuclei, , Excitation, , Glutamate, , Granule cells, , Purkinje cells, Stellate cells, Basket cells, , Excitation, , Glutamate/Aspartate, , Stellate cells, , Purkinje cells, , Inhibition, , GABA, , Basket cells, , Purkinje cells, , Inhibition, , GABA, , Golgi cells, , Granule cells, , Inhibition, , GABA, , Purkinje cells, , Cerebellar nuclei, Vestibular nuclei, , Inhibition, , GABA, , GABA = Gamma aminobutyric acid
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868 Section 10 t Nervous System, inhibit the activities of vestibular nuclei also., Thus, it is clear that the cerebellar cortex plays an, important role in modulating the excitatory signals, of following pathways:, i. From cerebellar nuclei to cerebral cortex via, thalamus, ii. From final common motor pathway via, brainstem and spinal cord., Because of this activity of cerebellar cortex,, movements of body are well organized and, coordinated., CEREBELLAR NUCLEI, Cerebellar nuclei are the masses of gray matter, scattered in the white matter of cerebellum. There are, four nuclei on either side (Fig. 150.3)., 1. Fastigial Nucleus, Fastigial nucleus is also known as nucleus fastigi., Phylogenetically, it is the oldest cerebellar nucleus. It, is placed near the midline on the roof of IV ventricle., , 1. Association fibers, Association fibers connect different regions of same, cerebellar hemisphere., 2. Commissural fibers, Commissural fibers connect the areas of both halves of, cerebellar cortex., 3. Projection fibers, Projection fibers are the afferent and efferent nerve, fibers which connect cerebellum with other parts of, central nervous system. Projection fibers of cerebellum, are arranged in three bundles (Fig. 150.4):, i. Inferior cerebellar peduncles between cerebellum and medulla oblongata, ii. Middle cerebellar peduncles between cerebellum, and pons, iii. Superior cerebellar peduncles between cerebellum and midbrain., i. Inferior Peduncles, , Globosus nucleus is situated lateral to nucleus fastigi., This is also known as nucleus globosus., , Inferior cerebellar peduncles are otherwise called, restiform bodies and contain predominantly afferent, fibers. These nerve fibers transmit the impulses from, tactile receptors, proprioceptors and receptors in, vestibular apparatus to cerebellum., , 3. Emboliform Nucleus, , ii. Middle Peduncles, , Emboliform nucleus is also called nucleus emboliformis. This nucleus is below the nucleus fastigi and, nucleus globosus., , Middle cerebellar peduncles are otherwise called brachia, pontis. These penduncles contain predominantly, the, afferent fibers. Most of the fibers of the middle cerebellar, peduncles are commissural fibers, which connect the, areas of both the halves of cerebellar cortex., , 2. Globosus Nucleus, , 4. Dentate Nucleus, Dentate nucleus is also called nucleus dentatus. It is, the largest cerebellar nucleus. As it is crenated, it is, called dentate nucleus. It is situated lateral to all the, other nuclei., WHITE MATTER OF CEREBELLUM, White matter of cerebellum is formed by afferent and, efferent nerve fibers. These nerve fibers are classified, into three groups., , FIGURE 150.3: Cerebellar nuclei, , FIGURE 150.4: Cerebellar peduncles
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Chapter 150 t Cerebellum 869, iii. Superior Peduncles, Superior cerebellar peduncles are otherwise called, the brachia conjunctivae and contain predominantly,, efferent fibers., , VESTIBULOCEREBELLUM, (ARCHICEREBELLUM), , nucleus globosus, nucleus emboliformis and nucleus, fastigi (Fig. 150.5). Fibers from these nuclei, reach the, vestibulocerebellum (flocculonodular node)., Vestibular nuclei in turn, receive fibers from vestibular apparatus situated in the inner ear, through vestibular division of cochlear (VIII cranial) nerve., Efferent Connections, , Vestibulocerebellum is connected with the vestibular, apparatus and so it is known as vestibulocerebellum., Since vestibulocerebellum is the phylogenetically oldest, part of cerebellum, it is also called archicerebellum., It is concerned with the maintenance of posture and, equilibrium., COMPONENTS, Vestibulocerebellum includes the flocculonodular lobe, that is formed by the nodulus of vermis and its lateral, extensions called flocculi (Fig. 150.1 and Table 150.3)., Uvula of vermis is also considered as the part of, vestibulocerebellum by some physiologists., CONNECTIONS, Afferent Connections, Vestibulocerebellar tract, Vestibulocerebellar tract is formed by the fibers arising, from the vestibular nuclei, situated in pons and medulla., It passes through the inferior cerebellar peduncle, of the same side and reaches the cerebellar nuclei,, , 1. Cerebellovestibular tract, Fibers of cerebellovestibular tract arise from the, flocculonodular lobe, pass through the inferior cerebellar, peduncle of the same side and terminate on the, vestibular nuclei in brainstem., Fibers from vestibular nuclei form medial and, lateral vestibulospinal tracts, which terminate on the, medial group of alpha motor neurons in the spinal cord., This pathway forms the part of medial system of motor, pathway (extrapyramidal system)., 2. Fastigiobulbar tract, Fibers of fastigiobulbar tract arise from fastigial nucleus,, pass through inferior cerebellar peduncle of the same, side and terminate on vestibular nuclei and reticular, formation in medulla oblongata., From vestibular nuclei, vestibulospinal tracts, (mentioned above) arise and terminate on alpha motor, neurons. From reticular formation, reticulospinal tract, arises and terminates on gamma motor neurons in the, spinal cord forming the part of medial motor system, (extrapyramidal system)., , TABLE 150.3: Components and connections of functional divisions of cerebellum, Division, , Components, , Afferent connections, , Efferent connections, , Vestibulocerebellum, , Flocculonodular lobe, (nodulus and flocculi), , Vestibulocerebellar tract, , 1. Cerebellovestibular tract, 2. Fastigiobulbar tract, , Spinocerebellum, , Lingula, Central lobe, Culmen, Lobulus simplex, Declive, Tuber, Pyramid, Uvula, Paraflocculi and, Medial portions of cerebral, hemispheres, , 1. Dorsal spinocerebellar tract, 2. Ventral spinocerebellar tract, 3. Cuneocerebellar tract, 4. Olivocerebellar tract, 5. Pontocerebellar tract, 6. Tectocerebellar tract, 7. Trigeminocerebellar tract, , 1. Fastigiobulbar tract, 2. Cerebelloreticular tract, 3. Cerebello-olivary tract, , Corticocerebellum, , Lateral portions of cerebral, hemispheres, , 1. Pontocerebellar tract, 2. Olivocerebellar tract, , 1. Dentatothalamic tract, 2. Dentatorubral tract
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870 Section 10 t Nervous System, , FIGURE 150.5: Connections of vestibulocerebellum. Red = Affernt connections, Blue = Efferent connections., , FUNCTIONS, Vestibulocerebellum regulates tone, posture and equilibrium by receiving impulses from vestibular apparatus., Vestibular apparatus sends information regarding, gravity, linear movement and angular acceleration to, vestibulocerebellum through vestibulocerebellar tract., Vestibulocerebellum, in turn, sends signals to spinal, cord via vestibulospinal and reticulospinal tracts., Mechanism of Action of Vestibulocerebellum, Normally, vestibular nuclei facilitate the movements, of trunk, neck and limbs through vestibulospinal tracts, and alpha motor neurons. Medullary reticular formation, inhibits the muscle tone through reticulospinal tract, and gamma motor neurons., However,, vestibulocerebellum, inhibits, both, vestibular nuclei and medullary reticular formation. As, a result, the movements of neck, trunk and limbs are, checked and the muscle tone increases. Because, of these effects, any disturbance in posture and, equilibrium is corrected., , In the lesion of vestibulocerebellum, there is a, reduction in muscle tone (hypotonia) and failure to, maintain posture and equilibrium., , SPINOCEREBELLUM, (PALEOCEREBELLUM), Spinocerebellum is connected with spinal cord and, hence the name. It forms the major receiving area, of cerebellum for sensory inputs. It is concerned with, the maintenance of muscle tone and anticipatory, adjustment of muscle contraction during movement., Spinocerebellum is also phylogenetically older part of, cerebellum. It is otherwise called paleocerebellum., COMPONENTS, Spinocerebellum consists of medial portions of, cerebellar hemisphere, paraflocculi and the parts, of vermis, viz. lingula, central lobe, culmen, lobulus, simplex, declive, tuber, pyramid and uvula (Fig. 150.1, and Table 150.3). However, some physiologists do not, consider uvula as a part of spinocerebellum.
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Chapter 150 t Cerebellum 871, CONNECTIONS, Afferent Connections, 1. Dorsal spinocerebellar tract, Dorsal spinocerebellar tract arises from Clarke’s, column of cells in the dorsal gray horn of spinal cord., It is uncrossed tract and reaches the spinocerebellum, through the inferior peduncle of same side (Fig. 150.6)., This tract conveys the proprioceptive information from, the limbs of same side regarding the position and, movements., , in the opposite side and reach the spinocerebellum, through superior cerebellar peduncle. This tract conveys, the information about the position and movements of, opposite limbs to spinocerebellum., 3. Cuneocerebellar tract, Cuneocerebellar tract arises from accessory cuneate, nucleus, situated lateral to cuneate nucleus in, medulla. It reaches the spinocerebellum through the, inferior cerebellar peduncle of the same side. This, tract conveys the proprioceptive impulses from upper, limb, upper trunk and neck to spinocerebellum., , 2. Ventral spinocerebellar tract, , 4. Olivocerebellar tract, , Fibers of ventral spinocerebellar tract arise from the, marginal cells in the dorsal gray horn of spinal cord. After, taking the origin, the fibers cross the midline, ascend, , Olivocerebellar tract is formed by climbing fibers arising, from the inferior olivary nucleus in medulla. After, taking origin, these fibers cross the midline and reach, , FIGURE 150.6: Connections of spinocerebellum. Red = Afferent connections, Blue = Efferent connections.
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872 Section 10 t Nervous System, the spinocerebellum through the inferior cerebellar, peduncle of the opposite side. This tract also gives, collaterals to cerebellar nuclei, particularly the globosus, nucleus and emboliform nucleus. Inferior olivary, nucleus receives afferent fibers from three sources:, i. Brainstem nuclei of same side, ii. Spinal cord through spino-olivary tract of same, side, iii. Cerebral cortex of opposite side., Olivocerebellar tract conveys proprioceptive, impulses from the body and output signals from, cerebral cortex to spinocerebellum., , cerebellar peduncle of same side and terminate in the, reticular formation., From reticular formation, reticulospinal tract arise and, terminate on the gamma motor neurons of spinal cord., , 5. Pontocerebellar tract, , FUNCTIONS, , Pontocerebellar tract arises from pontine nuclei,, crosses the midline and reaches the spinocerebellum, through the middle cerebellar peduncle of opposite, side. Pontine nuclei receive afferents from cerebral, cortex. Pontocerebellar tract conveys the information, to spinocerebellum about the motor signals discharged, from cerebral cortex., , Spinocerebellum regulates tone, posture and equilibrium, by receiving sensory impulses form tactile receptors,, proprioceptors, visual receptors and auditory receptors., Spinocerebellum is the receiving area for tactile,, proprioceptive, auditory and visual impulses. It also, receives the cortical impulses via pontine nuclei., Tactile and proprioceptive impulses are localized, in the spinocerebellum. Localization of tactile and, proprioceptive impulses in spinocerebellum is, determined by stimulating the tactile receptors and, the proprioceptors and by recording the electrical, responses in different parts of spinocerebellum. The, different parts of the body are represented in the, spinocerebellum in the following manner:, Lingula, : Coccygeal region, Central lobe, : Hind limb, Culmen, : Forelimb, Lobulus simplex : Face and head., In cerebral cortex, different parts of the body are, represented in an inverted manner. But in cerebellum,, different parts are represented in upright manner., Spinocerebellum regulates the postural reflexes by, modifying muscle tone. It facilitates the discharge from, gamma motor neurons in spinal cord via cerebellovestibulospinal and cerebello-reticulospinal fibers., Increased discharge from gamma motor neurons increases the muscle tone. Lesion, destruction or abolishing the function of spinocerebellum by cooling, causes, stoppage of discharge from gamma motor neurons,, resulting in hypotonia and disturbances in posture., Spinocerebellum also receives impulses from, optic and auditory pathway and helps in adjustment, of posture and equilibrium in response to visual and, auditory impulses., , 6. Tectocerebellar tract, Tectocerebellar tract arises from superior and, inferior colliculi of tectum in midbrain. It reaches the, spinocerebellum through superior cerebellar peduncle, of the same side. This tract carries visual impulses from, superior colliculus and auditory impulses from inferior, colliculus to spinocerebellum., 7. Trigeminocerebellar tract, Trigeminocerebellar tract is formed by the fibers, arising from mesencephalic nucleus of trigeminal, nerve. It reaches the spinocerebellum via superior, cerebellar peduncle of same side. This tract conveys, proprioceptive information from jaw muscles and, temporomandibular joint to spinocerebellum. It also, carries the sensory impulses from the periodontal, tissues (tissues around the teeth) to spinocerebellum., Efferent Connections, Cortex of spinocerebellum is projected into the nuclei, fastigi, emboliformis and globosus of cerebellum. Fibers, from these nuclei pass through following tracts:, 1. Fastigiobulbar tract, Fastigiobulbar tract arises from fastigial nucleus,, passes through superior cerebellar peduncle of same, side and ends in the reticular formation., , 3. Cerebello-olivary tract, Cerebello-olivary tract arises from the emboliform, and globosus nuclei and reaches the inferior olivary, nucleus of the same side by passing through the, superior cerebellar peduncle. From olivary nucleus, the, olivospinal tract arises and fibers of this tract end on the, alpha motor neurons of spinal cord., , 2. Cerebelloreticular tract, , CORTICOCEREBELLUM, (NEOCEREBELLUM), , Fibers of cerebelloreticular tract arise from the, emboliform and globosus nuclei, pass through superior, , Corticocerebellum is the largest part of cerebellum., Because of its connection with cerebral cortex, it is
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Chapter 150 t Cerebellum 873, called corticocerebellum or cerebrocerebellum. It is, phylogenetically newer part of cerebellum. So, it is also, called neocerebellum. It is concerned with planning,, programming and coordination of skilled movements., , 2. Olivocerebellar tract, , Afferent Connections, , Olivocerebellar tract arises from the inferior olivary, nucleus situated in medulla. It crosses the midline, and enters corticocerebellum via inferior cerebellar, peduncle of the opposite side. There it terminates on, the dentate nucleus and cerebellar cortex. This tract is, formed by climbing fibers., Inferior olivary nucleus receives impulses from, brainstem, spinal cord and cerebral cortex and conveys, these impulses to the corticocerebellum through the, olivocerebellar tract., , 1. Pontocerebellar tract, , Efferent Connections, , Pontocerebellar tract arises from pontine nuclei,, crosses the midline and enters corticocerebellum via, middle cerebellar peduncle (Fig. 150.7). It is the largest, tract in the body having about 20 million nerve fibers., Pontocerebellar tract is also called the corticopontocerebellar circuit. Because, it receives signals from, motor area of cerebral cortex and conveys those signals, to corticocerebellum. It helps the cerebellum in planning, the movements initiated by the cerebral cortex., , Output signals from corticocerebellum are relayed, mainly through the dentate nucleus. Fibers from dentate, nucleus pass through superior cerebellar peduncle,, cross the midline and form decussation with the fibers, of opposite side. After forming the decussation, these, fibers divide into two tracts:, 1. Dentatothalamic tract, 2. Dentatorubral tract., , COMPONENTS, Corticocerebellum includes the lateral portions of, cerebellar hemispheres (Fig. 150.1 and Table 150.3)., CONNECTIONS, , FIGURE 150.7: Connections of corticocerebellum. Red = Afferent connections, Blue = Efferent connections.
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874 Section 10 t Nervous System, 1. Dentatothalamic tract, After crossing, some of the fibers pass through red, nucleus without having any synapse and terminate in, lateral ventral nucleus of thalamus. Tract formed by, these fibers is called dentatothalamic tract. Thalamus in, turn, projects into the motor area of cerebral cortex via, thalamocortical fibers., 2. Dentatorubral tract, Remaining fibers terminate in the red nucleus of, opposite side as dentatorubral tract. Three tracts arise, from red nucleus:, i. Rubrothalamic tract: From red nucleus, this, tract ascends and terminates in lateral ventral, nucleus of thalamus. From here, thalamocortical, fibers arise and reach the cerebral cortex., ii. Rubroreticular tract: It descends down and, ends in reticular formation. Reticular formation, projects into spinal cord via reticulospinal tract., iii. Rubrospinal tract: Red nucleus also projects, directly into spinal cord through rubrospinal, tract., AFFERENT-EFFERENT CIRCUIT (CEREBROCEREBELLO-CEREBRAL CONNECTIONS), Afferent-efferent circuit is an important neuronal, pathway, involved in cerebellar control of voluntary, movements, initiated by the motor area of cerebral, cortex. This pathway includes two tracts:, , 1. Cerebropontocerebellar tract, 2. Dentatorubrothalamocortical tract., 1. Cerebropontocerebellar Tract, Fibers from motor areas 4 and 6 in frontal lobe of cerebral, cortex enter the pontine nuclei. These fibers are called, corticopontine fibers (Figs. 150.8 and 150.9). From, pontine nuclei, the pontocerebellar fibers arise and pass, through middle cerebellar peduncle of the opposite side, and terminate in the cerebellar cortex. This pathway is, called the cerebropontocerebellar tract., 2. Dentatorubrothalamocortical Tract, Cerebellar cortex is, in turn, connected to the dentate, nucleus. Fibers from the dentate nucleus pass via, superior cerebellar peduncle and end in red nucleus, of opposite side. These fibers are called dentatorubral, fibers. From red nucleus, the rubrothalamic fibers go to, thalamus. Thalamus is connected to areas 4 and 6 in, motor cortex of cerebrum by thalamocortical fibers. This, pathway is called dentatorubrothalamocortical tract., FUNCTIONS, Corticocerebellum is concerned with the integration and, regulation of well-coordinated muscular activities. It is, because of its afferent-efferent connection with cerebral, cortex through the cerebro-cerebello-cerebral circuit, (Table 150.4). Apart from its connections with cerebral, cortex, cerebellum also receives feedback signals from, the muscles through the nerve fibers of proprioceptors., , FIGURE 150.8: Cerebro-cerebello-cerebral circuit
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Chapter 150 t Cerebellum 875, , FIGURE 150.9: Schematic representation of cerebro-cerebello-cerebral circuit, , TABLE 150.4: Functions of cerebellum, Functions, 1. Regulation of tone,, posture and equilibrium, , 2. Regulation of coordinated, movements, , Division of cerebellum involved, , By receiving impulses from vestibular apparatus, , Vestibulocerebellum, , By receiving impulses from proprioceptors in muscles,, tendons and joints, tactile receptors, visual, receptors and auditory receptors, , Spinocerebellum, , i., ii., iii., iv., v., , Damping action, Control of ballistic movements, Timing and programming the movements, Servomechanism, Comparator function, , Mechanism of Action of Corticocerebellum, 1. Damping action, , Corticocerebellum, (Neocerebellum), , while doing any skilled or trained work like typing,, cycling, dancing, etc. Corticocerebellum plays an, important role in preplanning the ballistic movements, during learning process., , Damping action refers to prevention of exaggerated, muscular activity. This helps in making the voluntary, movements smooth and accurate. All the voluntary muscular activities are initiated by motor areas of cerebral, cortex. Simultaneously, corticocerebellum receives impulses from motor cortex as well as feedback signals from, the muscles, as soon as the muscular activity starts., Corticocerebellum, in turn, sends information (impulses) to cerebral cortex to discharge only appropriate, signals to the muscles and to cut off any extra impulses., Because of this damping action of corticocerebellum,, the exaggeration of muscular activity is prevented and, the movements become smooth and accurate. Literally,, the word damping means any effect that decreases the, amplitude of mechanical oscillation., , Corticocerebellum plays an important role in timing and, programming the movements, particularly during learning, process. While using a typewriter or while doing any other, fast-skilled work, a chain of movements occur rapidly, in a sequential manner. During the learning process of, these skilled works, corticocerebellum plans the various, sequential movements. It also plans schedule of time, duration of each movement and the time interval between, movements. All the information from corticocerebellum, are communicated to sensory motor area of cerebral, cortex and stored in the form of memory. So, after the, learning process is over, these activities are executed, easily and smoothly in a sequential manner., , 2. Control of ballistic movements, , 4. Servomechanism, , Ballistic movements are the rapid alternate movements, which take place in different parts of the body, , Servomechanism is the correction of any disturbance, or interference while performing skilled work. Once, , 3. Timing and programming the movements
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876 Section 10 t Nervous System, the skilled works are learnt, the sequential movements, are executed without any interruption. Cerebellum lets, the cerebral cortex to discharge the signals, which are, already programed and stored at sensory motor cortex, and does not interfere much. However, if there is any, disturbance or interference, the corticocerebellum, immediately influences the cortex and corrects the, movements., 5. Comparator function, Comparator function of the corticocerebellum is, responsible for the integration and coordination of the, various muscular activities., On one side, cerebellum receives the information, from cerebral cortex, regarding the cortical impulses, which are sent to the muscles. On the other side, it, receives the feedback information (proprioceptive, impulses) from muscles, regarding their actions under, the instruction of cerebral cortex., By receiving the messages from both ends,, corticocerebellum compares the cortical commands for, muscular activity and the actual movements carried out, by the muscles. If any correction is to be done, then,, corticocerebellum sends instructions (impulses) to the, motor cortex., Accordingly, cerebral cortex corrects or modifies, the signals to muscles, so that the movements, become accurate, precise and smooth. This function of, corticocerebellum is known as comparator function., Simultaneously, it also receives impulses from tactile, receptors, eye and ear. Such additional information, facilitates the comparator function of corticocerebellum., , APPLIED PHYSIOLOGY –, CEREBELLAR LESIONS, Cerebellar lesions may be due to tumor, abscess or an, injury. Excess alcohol ingestion also leads to cerebellar, lesions. Loss of functions of cerebellum also occurs due, to degenerative changes in cerebellar cortex, cerebellar, nuclei, cerebellar peduncles and spinocerebellar tracts., In general, during cerebellar lesions, there are, disturbances in posture, equilibrium and movements. In, unilateral lesion, symptoms appear on the affected side, because cerebellum controls the same (ipsilateral) side, of the body., Most of the disturbances are due to the damage to, corticocerebellum (neocerebellum) because in human, beings, it is larger than other divisions., , DISTURBANCES IN TONE AND POSTURE, 1. Atonia or Hypotonia, Atonia is the loss of tone and hypotonia is reduction in, tone of the muscle. Cerebellar lesion causes atonia or, hypotonia, depending upon the severity of the lesion., Atonia or hypotonia due to cerebellar lesion causes, disturbances in the postural reflexes., Cause for atonia or hypotonia during cerebellar, lesion is the loss of facilitatory impulses to gamma motor, neurons in the spinal cord via cerebello-vestibulospinal, and cerebello-reticulospinal fibers., 2. Attitude, Attitude of the body changes in unilateral lesion of the, cerebellum. Changes in the attitude are:, i. Rotation of head towards the opposite side, (unaffected side), ii. Lowering of shoulder on the same side, iii. Abduction of leg on the affected side. Leg is, rotated outward., iv. Weight of the body is thrown on leg of unaffected, side. So, trunk is bent with concavity towards, the affected side., 3. Deviation Movement, Deviation movement is the lateral deviation of arms, when both the arms are stretched and held in front of, the body, with closed eyes. In bilateral lesion, both the, arms deviate and in unilateral lesion, arm of the affected, side deviates., 4. Effect on Deep Reflexes, Pendular movements (Chapter 142) occur while, , eliciting a tendon jerk. These movements are very, common while eliciting the knee jerk or patellar tendon, reflex in the patients affected by cerebellar lesion., A tap on the patellar tendon when leg is hanging, freely causes a brisk extension of leg due to the, contraction of quadriceps muscle. In normal conditions,, after extension, the leg returns back to resting position, immediately. In cerebellar lesion, the leg shows, pendular movements., DISTURBANCES IN EQUILIBRIUM, While Standing, While standing, the legs are spread to provide a broad, base and the body sways side-to-side with oscillations, of the head.
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Chapter 150 t Cerebellum 877, While Moving – Gait, Gait means manner of walking. In cerebellar lesion, a, staggering, reeling and drunken-like gait is observed., DISTURBANCES IN MOVEMENTS, 1. Ataxia: Lack of coordination of movements., 2. Asynergia: Lack of coordination between different, groups of muscles such as protagonists, antagonists, and synergists., 3. Asthenia: Weakness, easy fatigability and slowness, of muscles., 4. Dysmetria: Inability to check exact strength and, duration of muscular contractions required for any, voluntary act. While reaching for an object, the arm, may overshoot (past pointing) or it may fall short of, the object. Overshooting is called hypermetria and, falling short is known as hypometria., 5. Intention tremor: Tremor that occurs while attempting to do any voluntary act. Refer Chapter 147 for, details of tremor., , 6. Astasia: Unsteady voluntary movements., 7. Nystagmus: To and fro movement of eyeball is, called nystagmus. Details of nystagmus are given, in Chapter 158., 8. Rebound phenomenon: When the patient attempts, to do a movement against resistance and if the, resistance is suddenly removed, the limb moves, forcibly in the direction in which the attempt was, made. It is called rebound phenomenon. It is due, to the absence of breaking action of antagonistic, muscle., 9. Dysarthria: Disturbance in speech. It is due to the, incoordination of various muscles and structures, involved in speech., 10. Adiadochokinesis: Ability to do rapid alternate, successive movements such as supination and, pronation of arm is called diadochokinesis. Inability, to do rapid alternate successive movements is called, adiadochokinesis. It is a common feature of cerebellar, lesion. It is also called dysdiadochokinesia.
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Chapter, , Basal Ganglia, , 151, , INTRODUCTION, COMPONENTS, , , , , CORPUS STRIATUM, SUBSTANTIA NIGRA, SUBTHALAMIC NUCLEUS OF LUYS, , CONNECTIONS, FUNCTIONS, , , , , , , , CONTROL OF MUSCLE TONE, CONTROL OF MOTOR ACTIVITY, CONTROL OF REFLEX MUSCULAR ACTIVITY, CONTROL OF AUTOMATIC ASSOCIATED MOVEMENTS, ROLE IN AROUSAL MECHANISM, ROLE OF NEUROTRANSMITTERS IN THE FUNCTIONS OF BASAL GANGLIA, , APPLIED PHYSIOLOGY – DISORDERS, , , , , , , , , , PARKINSON DISEASE, WILSON DISEASE, CHOREA, ATHETOSIS, CHOREOATHETOSIS, HUNTINGTON CHOREA, HEMIBALLISMUS, KERNICTERUS, , INTRODUCTION, , CORPUS STRIATUM, , Basal ganglia are the scattered masses of gray matter, submerged in subcortical substance of cerebral hemi, sphere (Fig. 151.1). Basal ganglia form the part of, extrapyramidal system, which is concerned with motor, activities., , Corpus striatum is a mass of gray matter situated at, the base of cerebral hemispheres in close relation to, thalamus (Fig. 151.2). Corpus striatum is incompletely, divided into two parts by internal capsule:, i. Caudate nucleus, ii. Lenticular nucleus., , COMPONENTS OF BASAL GANGLIA, , i. Caudate Nucleus, , Basal ganglia include three primary components:, 1. Corpus striatum, 2. Substantia nigra, 3. Subthalamic nucleus of Luys., , Caudate nucleus is an elongated arched gray mass,, lying medial to internal capsule. Throughout its length,, the caudate nucleus is related to lateral ventricle., Caudate nucleus has a head portion and a tail portion.
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Chapter 151 t Basal Ganglia 879, a. Outer putamen, b. Inner globus pallidus., Putamen and caudate nucleus are the phylogene, tically newer parts of corpus striatum and these two, parts are together called neostriatum or striatum., Globus pallidus is phylogenetically older part of corpus, striatum. And, it is called pallidum or paleostriatum., Globus pallidus has two parts, an outer part and an, inner part., SUBSTANTIA NIGRA, Substantia nigra is situated below red nucleus. It is, made up of large pigmented and small nonpigmented, cells. The pigment contains high quantity of iron., SUBTHALAMIC NUCLEUS OF LUYS, FIGURE 151.1: Basal ganglia, , Subthalamic nucleus is situated lateral to red nucleus, and dorsal to substantia nigra., , CONNECTIONS OF BASAL GANGLIA, Afferent and efferent connections of corpus striatum, (Figs. 151.3 and 151.4), substantia nigra and sub, thalamic nucleus of Luys are given in Table 151.1., In addition to afferent and efferent connections,, different components of corpus striatum of the same, side are interconnected by intrinsic fibers., 1. Putamen to globus pallidus, 2. Caudate nucleus to globus pallidus, 3. Caudate nucleus to putamen., Different components of corpus striatum in each, side are connected to those of the opposite side by, commissural fibers., , FIGURE 151.2: Corpus striatum, , Head is bulged into lateral ventricle and situated rostral, to thalamus. The tail is long and arched. It extends, along the dorsolateral surface of thalamus and ends, in amygdaloid nucleus., ii. Lenticular Nucleus, Lenticular nucleus is a wedgeshaped gray mass, sit, uated lateral to internal capsule. A vertical plate of, white matter called external medullary lamina, divides, lenticular nucleus into two portions:, , FIGURE 151.3: Afferent connections of corpus striatum
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880 Section 10 t Nervous System, ganglia decrease the muscle tone by inhibiting gamma, motor neurons through descending inhibitory reti, cular system in brainstem. During the lesion of basal, ganglia, muscle tone increases leading to rigidity., 2. CONTROL OF MOTOR ACTIVITY, i. Regulation of Voluntary Movements, , FIGURE 151.4: Efferent and intrinsic connections, of corpus striatum, , FUNCTIONS OF BASAL GANGLIA, Basal ganglia form the part of extrapyramidal system,, which is concerned with integration and regulation, motor activities. Various functions of basal ganglia are:, 1. CONTROL OF MUSCLE TONE, Basal ganglia control the muscle tone. In fact, gamma, motor neurons of spinal cord are responsible for deve, lopment of tone in the muscles (Chapter 157). Basal, , Movements during voluntary motor activity are initiated, by cerebral cortex. However, these movements are, controlled by basal ganglia, which are in close associa, tion with cerebral cortex. During lesions of basal ganglia,, the control mechanism is lost and so the movements, become inaccurate and awkward., Basal ganglia control the motor activities because, of the nervous (neuronal) circuits between basal ganglia, and other parts of the brain involved in motor activity., Neuronal circuits arise from three areas of the cerebral, cortex:, a. Premotor area, b. Primary motor area, c. Supplementary motor area (Chapter 152)., All these nerve fibers from cerebral cortex reach the, caudate nucleus. From here, the fibers go to putamen., Some of the fibers from cerebral cortex go directly to, putamen also. Putamen sends fibers to globus pallidus., Fibers from here run towards the thalamus, subthalamic, nucleus of Luys and substantia nigra. Subthalamic, nucleus and substantia nigra are in turn, projected into, thalamus. Now, the fibers from thalamus are projected, back into primary motor area and other two motor areas,, i.e. premotor area and supplementary motor area., , TABLE 151.1: Connections of basal ganglia, Component, , Afferent connections from, , Efferent connections to, , Corpus striatum, , 1. Thalamic nuclei to caudate nucleus and, putamen, 2. Cerebral cortex to caudate nucleus and, putamen, 3. Substantia nigra to putamen, 4. Subthalamic nucleus to globus pallidus, , 1. Thalamic nuclei, 2. Subthalamic nucleus, 3. Red nucleus, 4. Substantia nigra, 5. Hypothalamus, 6. Reticular formation (Most of the fibers, leave from globus pallidus), , Substantia nigra, , 1. Putamen, 2. Frontal lobe of cerebral cortex, 3. Superior colliculus, 4. Mamillary body of hypothalamus, 5. Medial and lateral lemnisci, 6. Red nucleus, , Putamen, , Subthalamic nucleus of Luys, , Globus pallidus, , 1. Globus pallidus, 2. Red nucleus
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Chapter 151 t Basal Ganglia 881, ii. Regulation of Conscious Movements, Fibers between cerebral cortex and caudate nucleus are, concerned with regulation of conscious movements. This, function of basal ganglia is also known as the cognitive, control of activity. For example, when a stray dog barks, at a man, immediately the person, understands the, situation, turns away and starts running., iii. Regulation of Subconscious Movements, Cortical fibers reaching putamen are directly concerned, with regulation of some subconscious movements,, which take place during trained motor activities, i.e., skilled activities such as writing the learnt alphabet,, paper cutting, nail hammering, etc., 3. CONTROL OF REFLEX, MUSCULAR ACTIVITY, Some reflex muscular activities, particularly visual, and labyrinthine reflexes are important in maintaining, the posture. Basal ganglia are responsible for the, coordination and integration of impulses for these reflex, activities., During lesion of basal ganglia, the postural move, ments, especially the visual and labyrinthine reflexes, become abnormal. These abnormal movements are, associated with rigidity. Rigidity is because of the loss, of inhibitory influence from the cerebral cortex on spinal, cord via basal ganglia., 4. CONTROL OF AUTOMATIC, ASSOCIATED MOVEMENTS, Automatic associated movements are the movements, in the body, which take place along with some motor, activities. Examples are the swing of the arms while, walking, appropriate facial expressions while talking or, doing any work. Basal ganglia are responsible for the, automatic associated movements., , Lesion in basal ganglia causes absence of these, automatic associated movements, resulting in poverty, of movements. Face without appropriate expressions, while doing any work is called mask-like face. Body with, out associated movements is called statue-like body., 5. ROLE IN AROUSAL MECHANISM, Globus pallidus and red nucleus are involved in arousal, mechanism because of their connections with reticular, formation. Extensive lesion in globus pallidus causes, drowsiness, leading to sleep., 6. ROLE OF NEUROTRANSMITTERS IN THE, FUNCTIONS OF BASAL GANGLIA, Functions of basal ganglia on motor activities are execu, ted by some neurotransmitters released by nerve end, ings within basal ganglia. Following neurotransmitters, are released in basal ganglia (Table 151.2):, 1. Dopamine released by dopaminergic fibers from, substantia nigra to corpus striatum (putamen and, caudate nucleus: dopaminergic nigrostriatal fibers):, deficiency of dopamine leads to parkinsonism, 2. Gammaaminobutyric acid (GABA) secreted by, intrinsic fibers of corpus striatum and substantia, nigra, 3. Acetylcholine released by fibers from cerebral, cortex to caudate nucleus and putamen, 4. Substance P released by fibers from globus, pallidus reaching substantia nigra, 5. Enkephalins released by fibers from globus, pallidus reaching substantia nigra, 6. Noradrenaline secreted by fibers between basal, ganglia and reticular formation, 7. Glutamic acid secreted by fibers from subthalamic, nucleus to globus pallidus and substantia nigra., Among these neurotransmitters, dopamine and, GABA are inhibitory neurotransmitters. So, the fibers, , TABLE 151.2: Neurotransmitters involved in the functions of basal ganglia, Neurotransmitter, 1. Dopamine, , Released by, Fibers from substantia nigra to corpus striatum, , Action, Inhibition, , 2. Gamma aminobutyric acid, , Intrinsic fibers of corpus striatum and substantia nigra, , Inhibition, , 3. Acetylcholine, , Fibers from cerebral cortex to caudate nucleus and putamen, , Excitation, , 4. Substance P, , Fibers from globus pallidus reaching substantia nigra, , Excitation, , 5. Enkephalins, , Fibers from globus pallidus reaching substantia nigra, , Excitation, , 6. Noradrenaline, , Fibers between basal ganglia and reticular formation, , Excitation, , 7. Glutamic acid, , Fibers from subthalamic nucleus to globus pallidus and substantia nigra, , Excitation
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882 Section 10 t Nervous System, releasing dopamine and GABA are inhibitory fibers. All, other neurotransmitters have excitatory function., , APPLIED PHYSIOLOGY –, DISORDERS OF BASAL GANGLIA, 1. PARKINSON DISEASE, Parkinson disease is a slowly progressive degenerative, disease of nervous system associated with destruction, of brain cells, which produce dopamine. It is named, after the discoverer James Parkinson. It is also called, parkinsonism or paralysis agitans. Great boxer, Mohammed Ali is affected by parkinsonism because, of repeated blows he might have received on head, resulting in damage of brain cells producing dopamine., Causes of Parkinson Disease, Parkinson disease occurs due to lack of dopamine, caused by damage of basal ganglia. It is mostly due to, the destruction of substantia nigra and the nigrostriatal, pathway, which has dopaminergic fibers. Damage of, basal ganglia usually occurs because of the following, causes:, i. Viral infection of brain like encephalitis, ii. Cerebral arteriosclerosis, iii. Injury to basal ganglia, iv. Destruction or removal of dopamine in basal, ganglia. It occurs mostly due to longterm treat, ment with antihypertensive drugs like reserpine., Parkinsonism due to the drugs is known as, drug-induced parkinsonism., , v. Unknown causes: Parkinsonism can occur, because of the destruction of basal ganglia due, to some unknown causes. This type of parkin, sonism is called idiopathic parkinsonism., , while doing any work. So, it is called static tremor or, resting tremor. It is also called drum-beating tremor, as, the movements are similar to beating a drum. Thumb, moves rhythmically over the index and middle fingers., These movements are called pill-rolling movements., ii. Slowness of movements, Over the time, movements start slowing down (bradykinesia) and it takes a long time even to perform a, simple task. Gradually the patient becomes unable to, initiate the voluntary activity (akinesia) or the voluntary, movements are reduced (hypokinesia). It is because of, hypertonicity of the muscles., iii. Poverty of movements, Poverty of movements is the loss of all automatic, associated movements. Because of absence of the, automatic associate movements, the body becomes, statue-like. The face becomes mask-like, due to absence, of appropriate expressions like blinking and smiling., iv. Rigidity, Stiffness of muscles occurs in limbs resulting in rigidity, of limbs. The muscular stiffness occurs because of, increased muscle tone which is due to the removal of, inhibitory influence on gamma motor neurons. It affects, both flexor and extensor muscles equally. So, the limbs, become more rigid like pillars. The condition is called, lead-pipe rigidity. In later stages the rigidity extends to, neck and trunk., v. Gait, Gait refers to manner of walking. The patient looses, the normal gait. Gait in Parkinson disease is called, festinant gait. The patient walks quickly in short steps, by bending forward as if he is going to catch up the, center of gravity., , Signs and Symptoms of Parkinson Disease, , vi. Speech problems, , Parkinson disease develops very slowly and the early, signs and symptoms may be unnoticed for months or, even for years. Often the symptoms start with a mild, noticeable tremor in just one hand. When the tremor, becomes remarkable the disease causes slowing or, freezing of movements followed by rigidity., Following are the common signs and symptoms of, Parkinson disease:, , Many patients develop speech problems. They may, speak very softly or sometimes rapidly. The words are, repeated many times. Finally, the speech becomes, slurred and they hesitate to speak., , i. Tremor, , viii. Dementia, , Refer Chapter 147 for details of tremor. In Parkinson, disease, the tremor occurs during rest. But it disappears, , In later stages, some patients develop dementia, (Chapter 162)., , vii. Emotional changes, The persons affected by Parkinson disease are often, upset emotionally.
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Chapter 151 t Basal Ganglia 883, Treatment for Parkinson Disease, As Parkinson disease is due to lack of dopamine, caused by damage of dopaminergic fibers, it is treated, by dopamine injection., Dopamine does not cross the bloodbrain barrier., So, another substance called levodopa (Ldopa), which crosses the bloodbrain barrier is injected., Ldopa moves into the brain and there it is converted, into dopamine. Since, Ldopa can be converted into, dopamine in liver, some side effects occur due to, excess dopamine content in liver and blood. So, along, with Ldopa, another substance called carbidopa is, administered. Carbidopa prevents the conversion, of Ldopa into dopamine and carbidopa cannot pass, through bloodbrain barrier. Thus, Ldopa moves into, the brain tissues and is converted into dopamine., Some of the symptoms of Parkinson disease such, as tremor are abolished by surgical destruction of basal, ganglia or thalamic nuclei., 2. WILSON DISEASE, Wilson disease is an inherited disorder characterized, by excess of copper in the body tissues. It is also, known as progressive hepatolenticular degeneration., This disease develops due to damage of the lenticular, nucleus particularly, putamen., In Wilson disease, copper is deposited in the liver,, brain, kidneys and eyes. Copper deposits cause damage, of tissues. And the affected organs stop functioning., In addition to symptoms of Parkinson disease, liver, failure and damage to the central nervous system are, the most predominant effects of this disorder. Wilson, disease is fatal if not treated early., , limbs. Chorea is due to the lesion in caudate nucleus, and putamen., 4. ATHETOSIS, Athetosis is another type of abnormal involuntary, movement, which refers to slow rhythmic and twisting, movements. It is because of the lesion in caudate, nucleus and putamen., 5. CHOREOATHETOSIS, Choreoathetosis is the condition characterized by aim, less involuntary muscular movements. It is due to com, bined effects of chorea and athetosis., 6. HUNTINGTON CHOREA, Huntington disease is an inherited progressive neural, disorder due to the degeneration of neurons secreting, GABA in corpus striatum and substantia nigra. This, disease starts mostly in middle age. It is characterized, by chorea, hypotonia and dementia. In severe cases, bilateral wasting of muscles occurs. It is otherwise called, Huntington disease, chronic progressive chorea,, degenerative chorea or hereditary chorea., , 7. HEMIBALLISMUS, Hemiballismus is a disorder characterized by violent, involuntary abnormal movements on one side of the, body involving mostly the arm. While walking, the arm, swings widely. These movements are called the flinging, movements. These movements are due to the release, phenomenon because of the absence of inhibitory, influence on movements. Hemiballismus occurs due to, degeneration of subthalamic nucleus of Luys., 8. KERNICTERUS, , 3. CHOREA, Chorea is an abnormal involuntary movement. Chorea, means rapid jerky movements. It mostly involves the, , Kernicterus is a form of brain damage in infants caused, by severe jaundice. Basal ganglia are the mainly, affected parts of brain. Refer Chapter 21 for details.
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Chapter, , Cerebral Cortex, , 152, , INTRODUCTION, HISTOLOGY OF CEREBRAL CORTEX, , , , LAYERS OF CEREBRAL CORTEX, PARTS OF CEREBRAL CORTEX, , LOBES OF CEREBRAL CORTEX, CEREBRAL DOMINANCE, , , CEREBRAL DOMINANCE AND HANDEDNESS, , BRODMANN AREAS, FRONTAL LOBE, , , , , PRECENTRAL CORTEX, PREFRONTAL CORTEX OR ORBITOFRONTAL CORTEX, APPLIED PHYSIOLOGY – FRONTAL LOBE SYNDROME, , PARIETAL LOBE, , , , , , SOMESTHETIC AREA I, SOMESTHETIC AREA II, SOMESTHETIC ASSOCIATION AREA, APPLIED PHYSIOLOGY, , TEMPORAL LOBE, , , , , , PRIMARY AUDITORY AREA, SECONDARY AUDITORY AREA, AREA FOR EQUILIBRIUM, APPLIED PHYSIOLOGY – TEMPORAL LOBE SYNDROME, , OCCIPITAL LOBE, , , , AREAS OF VISUAL CORTEX, APPLIED PHYSIOLOGY, , METHODS TO STUDY CORTICAL CONNECTIONS AND FUNCTIONS, , , , , , BY CUTTING OR DESTRUCTION OF NERVE CELL, BY RECORDING ELECTRICAL ACTIVITY – EVOKED POTENTIAL, BY PHYSIOLOGICAL NEURONOGRAPHY, BY SCANNING, , INTRODUCTION, Cerebral cortex is also called pallidum and it consists, , of two hemispheres. Surface area of cerebral cortex in, human beings is 2.2 sq m., Both the cerebral hemispheres are separated by, a deep vertical fissure (deep furrow or groove). The, , separation is complete anteriorly and posteriorly. But in, middle portion, the fissure extends only up to corpus, callosum. Corpus callosum is the broad band of, commissural fibers, connecting the two hemispheres., Surface of the cerebral cortex is characterized by, complicated pattern of sulci (singular = sulcus) and
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Chapter 152 t Cerebral Cortex 885, gyri (singular = gyrus). Sulcus is a slight depression or, groove and gyrus is a raised ridge., , HISTOLOGY OF CEREBRAL CORTEX, LAYERS OF CEREBRAL CORTEX, Cerebral cortex consists of gray matter that surrounds, the deeper white matter. It is formed by different types, of nerve cells along with their processes and neuroglia., It is not uniform throughout. It is thickest, i.e. 4.5 cm at, the precentral gyrus and thinnest at frontal and occipital, poles. According to Economo, the cerebral cortex is, formed by six layers of structures. Following are the, layers from outside to inside:, 1. Molecular or Plexiform Layer, Molecular layer has few small fusiform cells. It also, contains dendrites or axons from cells of deeper, layers., 2. External Granular Layer, External granular layer consists of large number of, closely packed small cells, which are round, polygonal, or triangular in shape. Dendrites of these cells pass into, molecular layer. Axons end in the deeper layers. Some, axons enter white substance of the hemisphere., 3. Outer Pyramidal Layer, Outer pyramidal layer is formed by pyramidal cells,, which are of two sizes. Medium sized pyramidal cells, are in the outer portion and larger pyramidal cells are in, deeper portion., , 4. Internal Granular Layer, Like external granular layer, this layer also has closely, packed smaller cells, which are stellate type. But, the, nerve fibers are more in this layer than in external, granular layer. This layer contains many horizontal, fibers, which appear as a white strip known as outer, strip., , 5. Ganglionic Layer or Internal Pyramidal Layer, Ganglionic layer or internal pyramidal layer consists of, pyramidal cells of graded sizes. It is well developed, in the precentral (motor) cortex. Pyramidal cells in, this region are otherwise known as Betz cells or giant, cells. This layer also contains cells of Martinotti., Martinotti cells are peculiar in that their axons pass, outward towards the surface of the cortex., 6. Fusiform Cell Layer, Fusiform cell layer is in contact with white matter of, cerebral hemisphere. It is composed of closely packed, small spindle-shaped cells., PARTS OF CEREBRAL CORTEX, Cerebral cortex is divided into two parts based on, phylogeny (evolutionary development of a species):, 1. Neocortex, 2. Allocortex., 1. Neocortex, Neocortex is the phylogenetically new structure of cerebral cortex. It is also called isocortex or neopallium., , FIGURE 152.1: Parts of cerebral cortex
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886 Section 10 t Nervous System, This part forms the major portion of cerebral cortex., Part of the cerebral cortex that has all six layers of, structures is called neocortex., 2. Allocortex, Allocortex is the phylogenetically oldest structure of, cerebral cortex. It has less than six layers of structures., It is divided into two divisions namely, archicortex and, paleocortex, which form the parts of limbic system, (Chapter 153)., , LOBES OF CEREBRAL CORTEX, In each hemisphere, there are three surfaces lateral,, medial and inferior surfaces. Neocortex of each cerebral hemisphere consists of four lobes (Figs. 152.1 to, 152.3):, 1. Frontal lobe, 2. Parietal lobe, 3. Occipital lobe, 4. Temporal lobe., Lobes of each hemisphere are demarcated by four, main fissures and sulci:, 1. Central sulcus or Rolandic fissure between frontal, and parietal lobes, , 2. Parieto-occipital sulcus between parietal and occipital lobe, 3. Sylvian fissure or lateral sulcus between parietal, and temporal lobes, 4. Callosomarginal fissure between temporal lobe, and limbic area., , CEREBRAL DOMINANCE, Cerebral dominance is defined as the dominance of, one cerebral hemisphere over the other in the control, of cerebral functions. Both the cerebral hemispheres, are not functionally equivalent. Some functional, asymmetries are well known., CEREBRAL DOMINANCE AND HANDEDNESS, Cerebral dominance is related to handedness, i.e., preference of the individual to use right or left hand., More than 90% of people are right handed. In these, individuals, the left hemisphere is dominant and it, controls the analytical process and language related, functions such as speech, reading and writing. Hence,, left hemisphere of these persons is called dominant or, categorical hemisphere., , FIGURE 152.2: Lobes of cerebral cortex
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Chapter 152 t Cerebral Cortex 887, , FIGURE 152.3: Functional regions on lateral surface of cerebral cortex, , Right hemisphere is called representational hemisphere since it is associated with artistic and visuo-, , FRONTAL LOBE OF CEREBRAL CORTEX, , spatial functions like judging the distance, determining, the direction, recognizing the tones, etc., Lesion in dominant hemisphere leads to language, disorders. Lesion in representational hemisphere causes, only mild effects like astereognosis., Left hemisphere is the dominant hemisphere in, about 75% of the right-handed persons. In the remaining, left-handed persons, right hemisphere controls the, language function. Some of these persons do not have, dominant hemisphere., , Frontal lobe forms one third of the cortical surface., It extends from frontal pole to the central sulcus and, limited below by the lateral sulcus. Frontal lobe of, cerebral cortex is divided into two parts:, A. Precentral cortex, which is situated posteriorly, B. Prefrontal cortex, which is situated anteriorly., , BRODMANN AREAS, Brodmann area is a region of cerebral cortex defined, on the basis of its cytoarchitecture. Cytoarchitecture, means organization of cells. Brodmann areas were, originally defined and numbered in 1909 by Korbinian, Brodmann depending upon the laminar organization, of neurons in the cortex. Some of these areas were, given specific names based on their functions. During, the period of a century Brodmann areas had been, extensively discussed and renamed., , PRECENTRAL CORTEX, Precentral cortex forms the posterior part of frontal, lobe. It includes the lip of central sulcus, whole of, precentral gyrus and posterior portions of superior,, middle and inferior frontal gyri. It also extends to the, medial surface., This part of cerebral cortex is also called excitomotor cortex or area, since the stimulation of different, points in this area causes activity of discrete skeletal, muscle. Precentral cortex is further divided into three, functional areas (Fig. 152.3):, 1. Primary motor area, 2. Premotor area, 3. Supplementary motor area.
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888 Section 10 t Nervous System, 1. Primary Motor Area, , Functions of primary motor area, , Primary motor area extends throughout the precentral, gyrus and the adjoining lip of central sulcus. Areas 4, and 4S are present here., , Primary motor area is concerned with initiation of, voluntary movements and speech., , Structure of primary motor area, , Area 4, , Though this area has all the six layers, the granular, layer is thin. Special structural feature of this layer is the, presence of giant pyramidal cells called Betz cells in, ganglionic layer., , It is a tapering strip of area situated in precentral gyrus, of frontal lobe. Broad end lies superiorly at the upper, border of hemisphere and most of the efferent fibers of, primary motor area arise from this area (Figs. 152.4 and, 152.5)., , Connections of primary motor area, , Function of area 4, , Efferent connections, , Area 4 is the center for movement, as it sends all, efferent (corticospinal) fibers of primary motor area., Through the fibers of corticospinal tracts, area 4, activates the lower motor neurons in the spinal cord. It, activates both α-motor neurons and γ-motor neurons, simultaneously by the process called coactivation, (Chapter 157)., Activation of α-motor neurons causes contraction of, extrafusal fibers of the muscles. Activation of γ-motor, neurons causes contraction of intrafusal fibers leading to increase in muscle tone., , i. Fibers of pyramidal tracts arise from the Betz cells., These fibers synapse with motor neurons in anterior, gray horn of opposite side (few fibers reach the, same side motor neurons) in spinal cord, ii. Frontopontine fibers from this area reach pontine, nuclei of same side, iii. Fibers are also projected to corpus striatum, red, nucleus, thalamus, subthalamus and reticular, formation, iv. Association fibers connect the primary motor area, to other areas of cortex., , Effect of stimulation of area 4, Electrical stimulation of area 4 causes discrete, , Afferent connections, Primary motor area receives fibers from dentate, nucleus (cerebellum) via red nucleus and thalamus., , isolated movements in the opposite side of the body., , The groups of muscles or single isolated muscle may, be activated depending upon the area stimulated., , FIGURE 152.4: Lateral surface of cerebral cortex
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Chapter 152 t Cerebral Cortex 889, , FIGURE 152.5: Medial surface of cerebral cortex, , Localization – homunculus, , Area 4S, , Muscles of various parts of the body are represented in, area 4 in an inverted way from medial to lateral surface., Lower parts of body are represented in medial surface, and upper parts of the body are represented in the, lateral surface., Order of representation from medial to lateral surface: Toes, ankle, knee, hip, trunk, shoulder, arm, elbow,, wrist, hand fingers and face. However, parts of the face, are not represented in inverted manner (Fig. 152.6)., Area 4 is concerned with contraction of discrete, muscles. It sends motor signals to the facial muscles, of both sides (bilateral) and the other muscles of the, opposite side (contralateral)., , Area 4S is called suppressor area. It forms a narrow, strip anterior to area 4. It scrutinizes and suppresses, the extra impulses produced by area 4 and inhibits, exaggeration of movements., , Effect of lesion of area 4, , Premotor area is similar to primary motor area in structure except for the absence of giant pyramidal cells in, ganglionic layer., , Effect of lesion or ablation of area 4 differs in different, species. In cats, the ability to walk is not affected. In monkeys, there is contralateral flaccid paralysis, hypotonia, and loss of reflexes. Myotatic reflexes reappear in a, short time. Recovery occurs only in proximal parts of, limbs but the digits remain permanently paralyzed., In man, the symptoms are severe than in monkeys., In unilateral lesion, paralysis occurs in contralateral side., Complete paralysis is rare. If both sides are affected,, the effect is more severe. Recovery occurs very slowly., During recovery, upper parts of body recover first., If area 4 is affected along with area 6, the effect is, very severe, causing hemiplegia with spastic paralysis., Hemiplegia means the paralysis in one half of the, body. In spastic paralysis, the muscles undergo spastic, contraction due to increased muscle tone., , 2. Premotor Area, Premotor area includes areas 6, 8, 44 and 45. The, premotor area is anterior to primary motor area in the, precentral cortex. The premotor area is concerned with, control of postural movements by sending motor signals, to axial muscles (muscles near the midline of the body)., Structure of premotor area, , Area 6, Area 6 is in the posterior portions of superior, middle, and inferior frontal gyri. It is subdivided into 6a and 6b., It gives origin to some of the pyramidal tract fibers. The, other connections are similar to those of area 4., Functions of area 6, Area 6 has two functions:, i. It is concerned with coordination of movements, initiated by area 4. It helps to make the skilled, movements more accurate and smooth., ii. It is believed to be the cortical center for extrapyramidal system.
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890 Section 10 t Nervous System, occur; but the movements become awkward. It also, produces grasping reflexes. Lesion involving areas 6, and area 4 produces severe symptoms of hemiplegia, with spastic paralysis., Area 8, Area 8 is called frontal eye field. It lies anterior to area 6, in the precentral cortex. It is concerned with movements, of eyeball., This area receives afferent fibers from dorsomedial, nucleus of thalamus and occipital lobe. It sends efferent, fibers to oculomotor nuclei in tegmentum of midbrain., Function of area 8, Frontal eye field is concerned with conjugate movement of eyeballs (Chapter 165). This area initiates, voluntary scanning movements of eyeballs and it is, independent of visual stimuli. It is also responsible for, opening and closing of eyelids, pupillary dilatation and, lacrimation., Effect of stimulation of area 8, Stimulation of this area causes conjugate movements, of eyeballs to the opposite side., Effect of lesion of area 8, Lesion of this area turns the eyes to the affected side., Conjugate movements of eyes are lost. However, pupils, and eyelids are not affected. In animals, while walking,, circular movements occur towards the affected side., Broca area, , FIGURE 152.6: Topographical arrangement (homunculus) of, motor areas in cerebral cortex, , Effect of stimulation of area 6, Electrical stimulation of area 6a in human being causes, the same effects as the stimulation of area 4. However,, the stimulus must be stronger to evoke response from, area 6. The effects of stimulation of this area are:, i. Stimulation of area 6a causes generalized, pattern of movements like rotation of head,, eyes and trunk towards the opposite side, ii. Stimulation of 6b produces rhythmic, complex, coordinated movements involving the muscles, of face, buccal cavity, larynx and pharynx., Effect of lesion of area 6, Lesion or removal of area 6 in monkeys leads to loss of, skilled movements. After the lesion, the recovery may, , Broca area is the motor area for speech. It includes, areas 44 and 45. Broca area is present in left hemisphere, (dominant hemisphere) of right-handed persons and, in the right hemisphere of left-handed persons. It is a, special region of premotor cortex situated in inferior, frontal gyrus. Area 44 is situated in pars triangularis, and 45 in pars opercularis of this gyrus., Function of Broca area, Broca area is responsible for movements of tongue, lips, and larynx, which are involved in speech., Effect of lesion of Broca area, Lesion in Broca area leads to aphasia (Chapter 162)., 3. Supplementary Motor Area, Supplementary motor area is situated in medial, surface of frontal lobe rostral to primary motor area., Various motor movements are elicited by electrical, stimulation of this area like raising the contralateral, arm, turning the head and eye and movements of, synergistic muscles of trunk and legs.
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Chapter 152 t Cerebral Cortex 891, Function of supplementary motor area, , Functions of Prefrontal Cortex, , Exact function of this area is not understood clearly. It is, suggested that it is concerned with coordinated skilled, , Earlier, this area was considered as inexcitable to, electrical stimulation. Hence, it was called the silent, area or association area. But, now it is known that, the stimulation of this area with low voltage electrical, stimulus causes changes in the activity of digestive,, cardiovascular, respiratory and excretory systems and, other autonomic functions. It also causes fear. Various, functions of prefrontal cortex are:, 1. It forms the center for the higher functions like, emotion, learning, memory and social behavior., Short-term memories are registered here., 2. It is the center for planned actions, 3. This area is the seat of intelligence; so, it is also, called the organ of mind, 4. It is responsible for the personality of the individuals, 5. Prefrontal cortex is responsible for the various, autonomic changes during emotional conditions,, because of its connections with hypothalamus and, brainstem., , movements., , Effect of lesion of supplementary motor area, During lesion in this area of human being, the head and, eyeballs turn towards the affected side., Destruction of this area in monkeys causes weak, grasping reflexes in contralateral side and bilateral, hypertonia of shoulder muscles. But, paralysis is not, noticed., PREFRONTAL CORTEX OR, ORBITOFRONTAL CORTEX, Prefrontal cortex is the anterior part of frontal lobe of, cerebral cortex, in front of areas 8 and 44. It occupies, the medial, lateral and inferior surfaces and includes, orbital gyri, medial frontal gyrus and the anterior, portions of superior, middle and inferior frontal gyri., Areas present in prefrontal cortex are 9, 10, 11, 12,, 13, 14, 23, 24, 29 and 32. Areas 12, 13, 14, 23, 24, 29, and 32 are in medial surface (Table 152.1). Areas 9, 10, and 11 are in lateral surface., Connections of Prefrontal Cortex, Afferent fibers, Afferent fibers of prefrontal cortex come from:, 1. Dorsomedial nucleus of thalamus, 2. Hypothalamus, 3. Corpus striatum, 4. Amygdala, 5. Midbrain., Areas 23, 24, 29 and 32 receive fibers from anterior, nucleus of thalamus. Area 32 receives fibers from suppressor area of precentral cortex also., Efferent fibers, Efferent fibers are projected to:, 1. Thalamus, 2. Hypothalamus, 3. Tegmentum, 4. Caudate nucleus, 5. Pons, 6. Temporal lobe of cerebral cortex., Area 13, along with hippocampus, uncus and, amygdala sends fibers to mamillary body of hypothalamus via fornix. This area is concerned with, emotional reactions., , Effect of Lesion of Prefrontal Cortex, Bilateral lesion or removal of prefrontal cortex in human, beings does not cause paralysis. It causes lack of, initiation and loss of mental alertness. Very little or no, change occurs in memory, judgment and intelligence., APPLIED PHYSIOLOGY – FRONTAL, LOBE SYNDROME, Injury or ablation of prefrontal cortex leads to a condition, called frontal lobe syndrome., Features of this syndrome are:, 1. Emotional instability: There is lack of restraint, leading to hostility, aggressiveness and restlessness, 2. Lack of concentration and lack of fixing attention, 3. There is lack of initiation and difficulty in planning, any course of action, 4. Impairment of recent memory occurs. However, the, memory of remote events is not lost., 5. Loss of moral and social sense is common and, there is loss of love for family and friends, 6. There is failure to realize the seriousness of the, condition. The subject has the sense of well-being, and also has flight of ideas., 7. Apart from mental defects, there are some functional, abnormalities also:, i. Hyperphagia (increased food intake), ii. Loss of control over sphincter of the urinary, bladder or rectum, iii. Disturbances in orientation, iv. Slight tremor.
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892 Section 10 t Nervous System, TABLE 152.1: Areas and connections of frontal lobe, Areas, , Afferent fibers from, , Primary motor areas 4, 4s, Precentral cortex, Premotor areas 6, 8, 44, 45, , 1. Cerebellum (Dentate nucleus, – via red nucleus), 2. Thalamus, , Supplementary area, , Prefrontal cortex, , Areas 9, 10, 11, 12, 13, 14, 29,, 23, 24, 32, , PARIETAL LOBE, Parietal lobe extends from central sulcus and merges, with occipital lobe behind and temporal lobe below. This, lobe is separated from occipital lobe by parieto-occipital, sulcus and from temporal lobe by Sylvian sulcus., Parietal lobe is divided into three functional areas:, A. Somesthetic area I, B. Somesthetic area II, C. Somesthetic association area., In addition to these three areas, a part of sensory, motor area is also situated in parietal lobe (see below)., SOMESTHETIC AREA I, Somesthetic area I is also called somatosensory area, I or primary somesthetic or primary sensory area. It, is present in the posterior lip of central sulcus, in the, postcentral gyrus and in the paracentral lobule., Areas of Somesthetic Area I, Somesthetic area I has three areas, which are called, areas 3, 1 and 2. Anterior part of this forms area 3 and, posterior part forms areas 1 and 2., Connections of Somesthetic Area I, Somesthetic area I receives sensory fibers from thalamus via parietal part of thalamic radiation., , 1. Thalamus, 2. Hypothalamus, 3. Corpus striatum, 4. Amygdala, 5. Midbrain, , Efferent fibers to, 1. Corticospinal tract, 2. Pons, 3. corpus striatum, 4. Red nucleus, 5. Thalamus, 6 Subthalamus, 7. Reticular formation, 1. Thalamus, 2. Hypothalamus, 3. Tegmentum, 4. Caudate nucleus, 5. Temporal lobe, , of parts of face from above downwards is eyelids,, nose, cheek, upper lip and lower lip (Fig. 152.7)., Functions of Somesthetic Area I, 1. Somesthetic area I is responsible for perception and, integration of cutaneous and kinesthetic sensations. It receives sensory impulses from cutaneous, receptors (touch, pressure, pain, temperature) and, proprioceptors of opposite side through thalamic, radiation. Area 1 is concerned with sensory perception. Areas 3 and 2 are involved in the integration of, these sensations., 2. This area sends sensory feedback to the premotor, area, 3. This area is also concerned with the movements of, head and eyeballs, 4. Discriminative functions: In addition to perception, of cutaneous and kinesthetic sensation, this area is, also responsible for recognizing the discriminative, features of sensations., Discriminative functions are:, i. Spatial recognition: Tactile localization, two, point discrimination and recognition of position, and passive movements of limbs, ii. Recognition of intensity of different stimuli, iii. Recognition of similarities and differences between the stimuli., , Localization – Homunculus, , Effect of Stimulation of Somesthetic Area I, , Different sensory areas of the body are represented in, postcentral gyrus (primary sensory area) in an inverted, manner as in the motor area. Toes are represented, in lowest part of medial surface, legs at the upper, border of hemispheres, then from above downwards, knee, thigh, hip, trunk, upper limb, neck and face., Representation of face is not inverted. Representation, , Electrical stimulation of somesthetic area I produces, vague sensations like numbness and tingling., Effects of Lesion of Somesthetic Area I, If lesion occurs only in the sensory area without involvement of thalamus, the sensations are still perceived.
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Chapter 152 t Cerebral Cortex 893, with perception of sensation. Thus, the sensory parts, of body have two representations, in somesthetic area, I and area II., SOMESTHETIC ASSOCIATION AREA, Somesthetic association area is situated posterior to, postcentral gyrus, above the auditory cortex and in front, of visual cortex. It has two areas, 5 and 7., Functions of Somesthetic Association Area, Somesthetic association area is concerned with synthesis of various sensations perceived by somesthetic, area I. Thus, the somesthetic association area forms the, center for combined sensations like stereognosis. Lesion, of this area causes astereognosis., Sensory Motor Area, Sensory area of cortex is not limited to postcentral gyrus, in parietal lobe. It extends anteriorly into motor area in, precentral gyrus of frontal lobe. Similarly, the motor, area is extended from precentral gyrus posteriorly into, postcentral gyrus., Thus, the precentral and postcentral gyri are knit, together by association neurons and are functionally, inter-related. So, this area is called sensory motor area., Function of sensory motor area is to store the timing, and programming of various sequential movements of, complicated skilled movements, which are planned by, neocerebellum (Table 152.2)., APPLIED PHYSIOLOGY, , FIGURE 152.7: Topographical arrangement (homunculus), of sensory areas in cerebral cortex, , But, the discriminative functions are lost. If thalamus, also is affected by lesion, there is loss of sensations in, the opposite side of the body., SOMESTHETIC AREA II, Somesthetic area II is situated in postcentral gyrus, below the area of face of somesthetic area I. A part, of this is buried in Sylvian sulcus. It is also known as, secondary somesthetic area or somatosensory area II., Functions of Somesthetic Area II, Somesthetic area II receives sensory impulses from, somesthetic area I and from thalamus directly. Though, the exact role of this area is not clear, it is concerned, , Lesion or ablation of parietal lobe (sensory cortex), results in the following disturbances:, 1. Contralateral disturbance of cutaneous sensations, 2. Disturbances in kinesthetic sensations, 3. Loss of tactile localization and discrimination., , TEMPORAL LOBE, Temporal lobe of cerebral cortex includes three, functional areas (Table 152.3):, A. Primary auditory area, B. Secondary auditory area or auditopsychic area, C. Area for equilibrium., PRIMARY AUDITORY AREA, Primary auditory area includes:, 1. Area 41, 2. Area 42, 3. Wernicke area.
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894 Section 10 t Nervous System, TABLE 152.2: Areas and connections of parietal lobe, Afferent fibers from, , Areas, , Efferent fibers to, , Somesthetic area I – 3, 1, 2 (Primary somesthetic area), , Thalamus, , Premotor area, , Somesthetic area II, , Somesthetic area I, Thalamus, , Motor area, , Somesthetic association areas 5, 7, , Somesthetic area I, , Somesthetic area I, , TABLE 152.3: Areas and connections of temporal lobe, Afferent fibers from, , Areas, Primary auditory areas 41, 42, Wernicke area, Auditopsychic area 22, Area for equilibrium, , 1. Medial geniculate body via auditory, radiation, 2. Pulvinar, , Efferent fibers to, 1. Medial geniculate body, 2. Pulvinar, , Areas 41 and 42 are situated in anterior transverse, gyrus and lateral surface of superior temporal gyrus., Wernicke area is in upper part of superior temporal, gyrus posterior to areas 41 and 42., , This area is concerned with interpretation of, auditory sensation along with Wernicke area. It is also, concerned with storage of memories of spoken words, (Chapter 162)., , Connections of Primary Auditory Area, , AREA FOR EQUILIBRIUM, , Afferent connections, , Area for equilibrium is in the posterior part of superior, temporal gyrus. It is concerned with the maintenance of, equilibrium of the body. Stimulation of this area causes, dizziness, swaying, falling and feeling of rotation., , Primary auditory are receives afferent fibers from:, 1. Medial geniculate body via auditory radiation, 2. Pulvinar of thalamus., Efferent connections, This area sends efferent fibers to:, 1. Medial geniculate body, 2. Pulvinar., Functions of Primary Auditory Area, Primary auditory area is concerned with perception of, auditory impulses, analysis of pitch and determination, of intensity and source of sound., Areas 41 and 42 are concerned only with the perception of auditory sensation (sound). Wernicke area is, responsible for the interpretation of auditory sensation., It carries out this function with the help of secondary, auditory area (area 22). Wernicke area is also, responsible for understanding the auditory information, about any word and sending the information to Broca, area (Chapter 162)., , APPLIED PHYSIOLOGY – TEMPORAL, LOBE SYNDROME, Temporal lobe syndrome is otherwise known as KluverBucy syndrome. It is observed in animals, particularly, monkeys after the bilateral ablation of temporal lobe, along with amygdala and uncus. It occurs in human, beings during bilateral lesions of these structures., Manifestations of this syndrome are:, 1. Aphasia (disturbance in speech: Chapter 162), 2. Auditory disturbances such as frequent attacks, of tinnitus, auditory hallucinations with sounds, like buzzing, ringing or humming. Tinnitus means, noise in the ear. Hallucination means feeling of a, particular type of sensation without any stimulus., 3. Disturbances in smell and taste sensations, 4. Dreamy states: The patients are not aware of their, own activities and have the feeling of unreality, 5. Visual hallucinations associated with hemianopia., , SECONDARY AUDITORY AREA, Secondary auditory area occupies the superior temporal, gyrus. It is also called or auditopsychic area or auditory, association area. It includes area 22., , OCCIPITAL LOBE, Occipital lobe is called the visual cortex. Areas and, connections of occipital lobe is given in Table 152.4.
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Chapter 152 t Cerebral Cortex 895, TABLE 152.4: Areas and connections of occipital lobe, Afferent fibers from, , Areas, , Efferent fibers to, , Primary visual area – 17, Visual association area – 18, , Lateral geniculate body, , Occipital eye field – 19, , AREAS OF VISUAL CORTEX, Occipital lobe consists of three functional areas:, 1. Primary visual area (area 17), 2. Secondary visual area or visuopsychic area (area, 18), 3. Occipital eye field (area 19)., Connections of Occipital Lobe, Occipital lobe receives afferent fibers from lateral, geniculate body. It sends efferent fibers to superior, colliculus and lateral geniculate body., Functions of Occipital Lobe, 1. Primary visual area (area 17) is concerned with perception of visual sensation, 2. Secondary visual area (area 18) is concerned with, interpretation of visual sensation and storage of, memories of visual symbols (Chapter 162), 3. Occipital eye field (area 19) is concerned with reflex, movement of eyeballs. It is also concerned with, associated movements of eyeballs while following, a moving object. (Table 152.5)., APPLIED PHYSIOLOGY, Lesion in the upper or lower part of visual cortex results, in hemianopia. Bilateral lesion leads to total blindness., Refer Chapter 168 for details., , METHODS TO STUDY CORTICAL, CONNECTIONS AND FUNCTIONS, BY CUTTING OR DESTRUCTION, OF NERVE CELL, 1. If the nerve cell body is destroyed, degenerative, changes occur throughout the axon arising from, it. By using Marchi staining technique, course of, the nerve fiber could be traced. If any part of motor, area is destroyed, the degeneration of the fibers, in the pyramidal tracts can be traced. If arm fibers, are involved, the degeneration occurs up to lower, cervical and upper thoracic level., , Superior colliculus, Lateral geniculate body, , 2. If an axon is cut, the nerve cell body (from which the, axon arises) undergoes chromatolysis. If any fiber, in pyramidal tract is cut, the chromatolysis occurs in, nerve cell body situated in motor cortex., Thus, this method is used to study connections and, localization in motor cortex. It is also used for the study, of connections of different parts of cerebral cortex., BY RECORDING ELECTRICAL ACTIVITY –, EVOKED POTENTIAL, When an impulse passes through a nerve, its route and, the termination can be determined by recording the, electrical potentials using microelectrodes at different, points along the course of the nerve fiber. This method, is used to trace certain pathways from or to the cortex,, particularly auditory pathway and pyramidal tract., Evoked Potential, Evoked potential is the electrical potential or electrical, response in a neuron or group of neurons in the brain, produced by an external stimulus. It is also called, evoked cortical potential., , When any receptor of skin or a sense organ (eye, or ear) is stimulated, the impulses pass through the, afferents and reach cerebral cortex. By using scalp, electrodes, the potentials developed in cortical areas, can be recorded. This method is used to determine, the functions of various cortical areas. It is also, used to map out the cortical representation of body, (localization) for sensory function., Evoked potential is recorded by placing the exploring electrode on the surface of the head over, the primary cortical area of the particular sensation., Indifferent electrode is placed on a distant area of head., In human beings small disk like electrodes are placed, on different areas of head by using a tape or washable, paste. Electrode cap, which is placed over the head, can also be used., Analysis and interpretation of the potential is done, by computer. Evoked potential is characterized by two, types of response.
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896 Section 10 t Nervous System, TABLE 152.5: Functions of cortical lobes, Lobe, Primary motor, area, , Frontal lobe, , Precentral cortex, , Premotor area, , Supplementary, motor area, , Parietal lobe, Temporal lobe, , Area 4, , Initiates of movements, , Area 4S, , Inhibits exaggeration of movements initiated by area 4, , Area 6, , Coordinates movements initiated by area 4, Acts as higher center for extrapyramidal system, , Area 8, , Frontal eye field, Concerned with conjugate movements of eyeballs, Concerned with voluntary movements of eyeballs, , Broca area:, Areas 44 and 45, , Initiates movements involved in speech; motor speech, area, , –, , Concerned with coordinated skilled movements, , Areas 9, 10, 11, 12, 13, 14, 23, 24, 29, and 32, , Concerned with emotion, learning, memory and social, behavior, Act as the center for planned actions, Form seat of intelligence, Initiate autonomic changes during emotional conditions, , Area 1, , Perceives cutaneous and kinesthetic sensations, , Areas 3 and 2, , Integrate cutaneous and kinesthetic sensations, , Areas 3, 2 and 1, , Send feedback to premotor area, Concerned with movements of head and eyeballs, Concerned with recognition of discriminative features of, sensations, , Somesthetic, area II, , –, , Perceives cutaneous and kinesthetic sensations, , Somesthetic, association, area, , Areas 5 and 7, , Synthesize sensations perceived by somesthetic area I, (forms the center for combined sensations), , Areas 41 and 42, , Perceive auditory sensation, , Wernicke area, , Interprets auditory sensation (along with area 22), , Secondary, auditory area, , Area 22, , Interprets auditory sensation (along with Wernicke area), , Area for, equilibrium, , –, , Concerned with maintenance of equilibrium of body, , Primary visual, area, , Area 17, , Perceives visual sensation, , Secondary visual, area, , Area 18, , Interprets visual sensation, , Occipital eye field, , Area 19, , Concerned with reflex movement of eyeballs, Concerned with associated movements of eyeballs, while following a moving object, , Prefrontal cortex, , Occipital lobe, , Functions, , Somesthetic, area I, , Primary auditory, area
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Chapter 152 t Cerebral Cortex 897, 1. Primary evoked potential, When the stimulus is applied to the receptor or sense, organ, the primary evoked potential appears after, a latent period of 5 to 10 milliseconds. It includes a, positive wave followed by a small negative wave., Primary evoked potential is highly localized and, appears specifically on the cortical surface where the, particular sensory pathway terminates., 2. Diffuse secondary evoked potential, Finally another larger and prolonged positive wave, called secondary evoked potential is recorded. It is not, localized. It appears on the diffused areas of cortex., Thus, the evoked potential includes P1-N1-P2, sequence, i.e. first positive wave – first negative wave –, second positive wave., , 2. Auditory evoked potential that is recorded when, auditory receptors are stimulated by listening to a, test sound, 3. Somatosensory evoked potential, which is recorded, when the somatic nerves of the limbs are stimulated, by electrical stimulus., BY PHYSIOLOGICAL NEURONOGRAPHY, When a small piece of blotting paper soaked in, strychnine solution is placed over cerebral cortex, the, , nerve cells are stimulated by strychnine. The impulses, discharged by these nerve cells pass through the, axons and reach the termination in other part of cortex, or other part of brain. By recording these impulses, the, connections of cortex can be studied., BY SCANNING, , Diagnostic Uses of Evoked Potential, An evoked potential test determines the functional, status of a nervous pathway. It also measures the time, taken by the nerves to respond to stimulation. Intensity, of response is also measured. Nerves from different, areas of the body may be tested. However, three types, of evoked potentials are commonly used in diagnosis., 1. Visual evoked potential, which is recorded when, the visual receptors are stimulated by looking at a, test pattern, , Nowadays, the functional activities of cerebral cortex, or other parts of the brain are determined by scanning., Due to the fast development of technology, many, sophisticated scanning methods are being introduced., Three such methods used widely are:, 1. Computerized axial tomography (CAT), 2. Positron emission tomography (PET), 3. Magnetic resonance imaging (MRI)., Refer Chapter 109 for details of these scanning, methods.
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Chapter, , Limbic System, , 153, , INTRODUCTION, COMPONENTS, , , , , , ARCHICORTICAL STRUCTURES, PALEOCORTICAL STRUCTURES, JUXTALLOCORTICAL STRUCTURES, SUBCORTICAL STRUCTURES, , CONNECTIONS, FUNCTIONS, , , , , , , , , , , OLFACTION, REGULATION OF ENDOCRINE GLANDS, REGULATION OF AUTONOMIC FUNCTIONS, REGULATION OF FOOD INTAKE, CONTROL OF CIRCADIAN RHYTHM, REGULATION OF SEXUAL FUNCTION, ROLE IN EMOTIONAL STATE, ROLE IN MEMORY, ROLE IN MOTIVATION, , INTRODUCTION, , 2. Paleocortical structures, 3. Juxtallocortical structures, 4. Subcortical structures., , Limbic system is a complex system of cortical and, subcortical structures that form a ring around the, hilus of cerebral hemisphere. Limbus means ring., It is also known as limbic lobe. Earlier, it was called, , ARCHICORTICAL STRUCTURES, , rhinencephalon., , Archicortex forms allocortex along with paleocortex, , In terms of evolutionary development (phylogeny),, limbic system is one of the oldest parts of the brain and, it is related to olfactory lobe. It is found as a prominent, structure in fish, amphibians, reptiles and mammals., Limbic system is primarily related to emotional part, of our life and is extensively concerned with memory., , (Chapter 152). Archicortex is the phylogenetically oldest, structure. It is concerned with memory., , COMPONENTS OF LIMBIC SYSTEM, Structures of limbic system are classified into four, groups (Fig. 153.1):, 1. Archicortical structures, , PALEOCORTICAL STRUCTURES, Paleocortex is in between archicortex and neocortex., It is concerned with olfaction., JUXTALLOCORTICAL STRUCTURES, Juxtallocortex or mesocortex is situated between paleocortex and neocortex.
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Chapter 153 t Limbic System 899, , FIGURE 153.1: Components of limbic system, , SUBCORTICAL STRUCTURES, , Papez Circuit, , Structures situated below the level of cortex are, called subcortical structures. Limbic system includes, six subcortical structures (Figs. 153.1 and 153.2)., , Papez circuit is the interconnections between various, structures of limbic system, which form a complex of, closed circuit. This circuit was described by Papez., Hippocampus is connected to mamillary bodies of, hypothalamus via fornix. Mamillary bodies are connected to anterior thalamic nucleus via mamillothalamic tract. Anterior thalamic nucleus is projected into, cingulate gyrus through medial thalamocortical fibers., Cingulate gyrus is in turn connected to hippocampus, (Fig. 153.3). Papez circuit plays a role in memory, encoding (Chapter 162)., , CONNECTIONS OF LIMBIC SYSTEM, Connections of limbic system are complex. Following, are the major (afferent and efferent) connections of, limbic system:, 1. Fornix: It includes fibers connecting:, i. Hippocampus and septal nuclei with the, mamillary body, ii. Hippocampus with hypothalamic nuclei., 2. Lateral hypothalamus receives afferent fibers from:, i. Hippocampus, ii. Septal nuclei, iii. Olfactory tubercle, iv. Head of caudate nucleus, v. Piriform area, vi. Periamygdaloid area., 3. Caudate nucleus receives fibers from:, i. Cingulate gyrus, ii. Intralaminar nuclei of thalamus., 4. Brainstem reticular formation receives fibers from:, i. Hippocampus, ii. Cingulate gyrus., 5. Papez circuit., , FUNCTIONS OF LIMBIC SYSTEM, 1. OLFACTION, Piriform cortex and amygdaloid nucleus form the, olfactory centers. In lower animals, the amygdaloid, nucleus is concerned primarily with olfaction., 2. REGULATION OF ENDOCRINE GLANDS, Hypothalamus plays an important role in regulation of, endocrine secretion (Chapter 66)., 3. REGULATION OF AUTONOMIC FUNCTIONS, Hypothalamus plays an important role in regulating, the autonomic functions (Chapter 149) such as:, i. Heart rate, ii. Blood pressure
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900 Section 10 t Nervous System, , FIGURE 153.2: Major components of limbic system, , iii. Water balance, iv. Body temperature., 4. REGULATION OF FOOD INTAKE, Along with amygdaloid complex, the feeding center and, satiety center present in hypothalamus regulate food, intake (Chapter 149)., 5. CONTROL OF CIRCADIAN RHYTHM, FIGURE 153.3: Papez circuit, , Hypothalamus is taking major role in the circadian, fluctuations of various physiological activities (Chapter, 149)., 6. REGULATION OF SEXUAL FUNCTIONS, Hypothalamus is responsible for maintaining sexual, functions in both man and animals (Chapter 149)., 7. ROLE IN EMOTIONAL STATE, Emotional state of human beings is maintained by, hippocampus along with hypothalamus (Chapter 149)., , 8. ROLE IN MEMORY, Hippocampus and Papez circuit play an important role, in memory (Chapter 162)., 9. ROLE IN MOTIVATION, Reward and punishment centers present in hypothalamus and other structures of limbic system are, responsible for motivation and the behavior pattern of, human beings (Chapter 149)., Refer Chapter 149 for details of the hypothalamic, functions.
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Reticular Formation, , Chapter, , 154, , DEFINITION, SITUATION, ORGANIZATION OF RETICULAR FORMATION, , , , , , , RAPHE GROUP, PARAMEDIAN GROUP, LATERAL GROUP, MEDIAL GROUP, INTERMEDIATE GROUP, , DIVISIONS OF RETICULAR FORMATION, , , , , NUCLEI OF MEDULLARY RETICULAR FORMATION, NUCLEI OF PONTINE RETICULAR FORMATION, NUCLEI OF MIDBRAIN RETICULAR FORMATION, , CONNECTIONS, , , , AFFERENT CONNECTIONS, EFFERENT CONNECTIONS, , FUNCTIONS, , , , ASCENDING RETICULAR ACTIVATING SYSTEM (ARAS), DESCENDING RETICULAR SYSTEM, , DEFINITION, , 1. RAPHE GROUP, , Reticular formation is a diffused mass of neurons and, nerve fibers, which form an ill-defined meshwork of, reticulum in central portion of the brainstem., , Raphe group of nuclei are situated along the midline, of the brainstem forming a continuous column. Raphe, nuclei secrete serotonin (5-hydroxytryptamine), which, is an inhibitory neurotransmitter., , SITUATION OF, RETICULAR FORMATION, , 2. PARAMEDIAN GROUP, , Reticular formation is situated in brainstem. It extends, downwards into spinal cord and upwards up to thalamus, and subthalamus., , ORGANIZATION OF, RETICULAR FORMATION, Reticular formation is constituted by 5 groups of nuclei., All these nuclei are structurally and functionally distinct., , Paramedian group includes nucleus reticularis paramedianus and pontine reticulotegmental nucleus., These nuclei are concerned with motor functions., 3. LATERAL GROUP, Lateral group of nuclei are situated in the lateral one, third of the tegmentum. It consists of nuclei with small, (parvocellular) cells. Neurons of these nuclei receive, sensory signals from the cranial nerves, cerebellum, and spinal cord.
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902 Section 10 t Nervous System, 4. MEDIAL GROUP, Medial group of nuclei are situated in the medial two, third of the tegmentum. It consists of nuclei with small, cells and giant (gigantocellular) cells. Nuclei of this group, form the major output of the reticular formation and send, fibers to the hypothalamus, thalamus and spinal cord., These nuclei are associated with motor functions., 5. INTERMEDIATE GROUP, Intermediate group of nuclei are present only in the, medulla. It is situated between the lateral and medial, groups of nuclei. These nuclei are concerned with, autonomic regulation of respiration, heart rate and, blood pressure., , DIVISIONS OF RETICULAR FORMATION, Reticular formation is divided into three divisions based, on the location in brainstem:, A. Medullary reticular formation, B. Pontine reticular formation, C. Midbrain reticular formation., Each division of reticular formation has its own, collection of nuclei., NUCLEI OF MEDULLARY, RETICULAR FORMATION, 1., 2., 3., 4., 5., 6., 7., 8., , CONNECTIONS OF, RETICULAR FORMATION, AFFERENT CONNECTIONS, Reticular formation receives collaterals from almost all, the ascending sensory pathways. It also receives fibers, from different parts of the brain (Fig. 154.1):, 1. Optic pathway, 2. Olfactory pathway, 3. Auditory pathway, 4. Taste pathway, 5. Spinal and trigeminal pathways carrying touch, sensation, 6. Pathways for pain, temperature, vibration and kinesthetic sensations, 7. Cerebral cortex, 8. Cerebellum, 9. Corpus striatum, 10. Thalamic nuclei., EFFERENT CONNECTIONS, Reticular formation sends fibers to the following parts of, central nervous system (Fig. 154.2):, 1. Cerebral cortex, 2. Diencephalon: Thalamus, hypothalamus and subthalamus, , Lateral reticular nucleus, Ventral reticular nucleus, Dorsal reticular nucleus, Gigantocellular reticular nucleus, Paragigantocellular reticular nucleus, Paramedian reticular nucleus, Parvocellular reticular nucleus, Magnocellular reticular nucleus., , NUCLEI OF PONTINE, RETICULAR FORMATION, 1., 2., 3., 4., 5., 6., 7., , Nucleus reticularis pontis oralis, Nucleus reticularis pontis caudalis, Locus ceruleus nucleus, Subceruleus reticular nucleus, Tegmenti pontis reticular nucleus, Pedunculopontine reticular nucleus, Nucleus reticular cuneiformis., , NUCLEI OF MIDBRAIN, RETICULAR FORMATION, 1. Red nucleus, 2. Nucleus tegmental pedunculopontis, 3. Nucleus reticular subcuneiformis., , FIGURE 154.1: Afferent connections of reticular formation
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Chapter 154 t Reticular Formation 903, Any type of sensory impulses such as impulses, of proprioception, pain, auditory, visual, taste and, olfactory sensations cause sudden activation of the, ARAS producing arousal phenomenon in animals, and human beings. Even the impulses of visceral, sensations activate this system. Sympathetic stimulation and adrenaline cause arousal by affecting, midbrain., 2. The ARAS also causes emotional reactions, 3. The ARAS plays an important role in regulating, the learning processes and the development of, conditioned reflexes., , Mechanism of Action of ARAS, , FIGURE 154.2: Efferent connections of reticular formation, , Impulses of all the sensations reach cerebral cortex, through two channels:, 1. Classical sensory pathways, 2. Ascending reticular activating system., 1. Classical or specific sensory pathways, , 3. Midbrain: Red nucleus, tectum and substantia nigra, 4. Cerebellum, 5. Spinal cord., , FUNCTIONS OF RETICULAR FORMATION, Based on functions, reticular formation along with its, connections is divided into two systems:, A. Ascending reticular activating system, B. Descending reticular system., , Classical sensory pathways are the pathways, which, transmit the sensory impulses from receptors to, cerebral cortex via thalamus. Some of the pathways, carry impulses of a particular sensation only. For, example, auditory stimulus transmitted by auditory, pathway reaches the auditory cortex via thalamus and, causes perception of sound. Such classical sensory, pathways are called specific sensory pathways., , ASCENDING RETICULAR, ACTIVATING SYSTEM, Ascending reticular activating system (ARAS) begins in, lower part of brainstem, extends upwards through pons,, midbrain, thalamus and finally projects throughout the, cerebral cortex. It projects into cerebral cortex in two, ways:, 1. Via subthalamus, 2. Via thalamus., The ARAS receives fibers from the sensory, pathways via long ascending spinal tracts (Fig. 154.3)., Functions of ARAS, 1. The ARAS is concerned with arousal phenomenon,, alertness, maintenance of attention and wakefulness. Hence, it is called ascending reticular, activating system. Stimulation of midbrain reticular, formation produces wakefulness by generalized, activation of entire brain including cerebral cortex,, thalamus, basal ganglia and brainstem., , FIGURE 154.3: Ascending reticular formation
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904 Section 10 t Nervous System, , FIGURE 154.4: Functional divisions of reticular formation, , 2. Ascending reticular activating system, or non-specific sensory pathway, All the sensory pathways send collaterals to ARAS,, which is a multisynaptic relay system. These collaterals, project in diffused areas of ARAS. So, the sensory, impulses transmitted via the collaterals reach different, parts of ARAS. It also receives afferents from spinal, cord directly in the form of spinoreticular tract. ARAS, in turn sends the impulses to almost all the areas of, cerebral cortex and other parts of brain. Hence, this, pathway is called the non-specific sensory pathway., Non-specific projection of ARAS into the cortex, is responsible for the arousal, alertness and wakefulness. Sensory impulses transmitted directly to, cortex via classical pathway causes perception of only, the particular sensation. Whereas, the impulses transmitted to cortex via ARAS do not cause the perception, of any particular sensation, but cause the generalized, activation of almost all the areas of cerebral cortex and, other parts of brain. This leads to reactions of arousal,, alertness and wakefulness., The ARAS is in turn controlled by the feedback, signals from cerebral cortex. Also, an inhibitory system, controls the activities of ARAS. Inhibitory system involves posterior hypothalamus, intralaminar and anterior, thalamic nuclei and medullary area at the level of, tractus solitarius., Tumor or lesion in ARAS leads to sleeping, sickness or coma. The impact of head injury on ARAS, also causes coma., , DESCENDING RETICULAR SYSTEM, Descending reticular system includes reticular formation, in brainstem, reticulospinal tract and reticular formation, in spiral cord., It modifies the activities of spinal motor neurons., Functionally, descending reticular system is divided into, two subdivisions (Fig. 154.4):, 1. Descending facilitatory reticular system, 2. Descending inhibitory reticular system., Descending Facilitatory Reticular System, Descending facilitatory reticular system is present in, upper and lateral reticular formation. Its functions are:, i. Facilitation of somatomotor activities, a. Descending facilitatory reticular system maintains muscle tone by exciting the gamma motor, neurons in spinal cord; stimulation of this area, causes increased muscle tone, b. It facilitates the movements of the body. Stimulation of this part of reticular system causes, exaggerated movements., c. It plays a role in wakefulness and alertness by, activating the ARAS., ii. Facilitation of vegetative functions, Descending facilitatory reticular system is the center for facilitation of the autonomic functions such, as cardiac function, blood pressure, respiration,, gastrointestinal function and body temperature.
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Chapter 154 t Reticular Formation 905, Descending Inhibitory Reticular System, Descending inhibitory reticular system is located in a, small area in lower and medial reticular formation. Its, functions are:, i. Control of somatomotor activities, a. Descending inhibitory reticular system plays, an important role in the control of muscle, tone. By receiving signals from basal ganglia,, it inhibits the gamma motor neurons of spinal, cord and decreases muscle tone. Stimulation, of this area causes decreased muscle tone., , b. It is responsible for smoothness and accuracy, of voluntary movements. It controls the muscular, activity by inhibiting the motor neurons of spinal, cord., c. It also controls the reflex movements., ii. Control of vegetative functions, Descending inhibitory reticular system is the center, for inhibition of several autonomic functions such, as cardiac function, blood pressure, respiration,, gastrointestinal function and body temperature.
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Preparations of Animals, for Experimental Studies, , , , , , , Chapter, , 155, , INTRODUCTION, DECORTICATE PREPARATION, DECEREBRATE PREPARATION, THALAMIC (MIDBRAIN) PREPARATION, SPINAL PREPARATION, , INTRODUCTION, Various functions of nervous system, particularly the, maintenance of posture and equilibrium are studied by, observing the effects of sections or lesions at different, levels of central nervous system in animals. Commonly, used animals are monkeys, dogs and cats., , DECORTICATE PREPARATION, Decorticate animal is the one without cerebral cortex., It is prepared by removing whole cerebral cortex, leaving basal ganglia intact. It is also prepared by, removing all the connections of cerebral cortex., Effect of decortication varies with species and the, conditions under which the animal is being examined., In a dog or cat, when the animal is on its feet,, posture is normal. Muscle tone is normally distributed, and it is present equally in flexor and extensor muscles., Movements during walking can be performed by reflex, activity. If the animal is suspended in the air, there is, severe hyperextension of all the limbs. In decorticate, monkey, the tone is gravely affected. Movements of, walking cannot occur by reflex activity., Effects in Man, In man, decorticate condition is caused by intracranial, hemorrhage, head injury, brain abscess or brain tumor., Decorticate condition is called decorticate rigidity., Decorticate Rigidity, Decorticate rigidity is the abnormal postural changes, that involve rigid extension of the lower limbs and flexion, , of the upper limbs at elbow joint across the chest. Wrists, and fingers are also flexed. Posture may develop on one, side or both sides of the body., Effects on Reflexes, Reflexes at the neck level can be elicited. These neck, reflexes affect the body also. When the neck is turned to, right, there is flexion of the lower and upper limbs on the, opposite side. But, on the same side, there is extension, of the limbs. It may be due to the cutting or lesion of, direct corticospinal tract. Some fibers of corticospinal, tract are known to have inhibitory influence on the, extensor muscles., , DECEREBRATE PREPARATION, It is prepared by removing all connections of cerebral, hemispheres at the level of midbrain, by sectioning in, between the superior colliculus and inferior colliculus., This preparation is characterized by a state of stiffness, or rigidity, which is known as decerebrate rigidity,, resembling the effects of upper motor neuron lesion., This preparation was first done by Nobel laureate, Sir, Charles Sherrington in cat., Decerebrate Rigidity, Decerebrate rigidity is the rigid extension of all the, limbs due to decerebration. This type of rigidity is, well pronounced in the extensor muscles. The term, decerebrate rigidity was coined by Sherrington in 1897.
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Chapter 155 t Preparations of Animals for Experimental Studies 907, Reason for decerebrate rigidity is the release of, the centers, situated below the section, from higher, inhibitory controls. The inhibitory area is 4S. It is situated, in the motor cortex of cerebrum, just anterior to area 4, and behind area 6. In this area, Betz cells are absent., From here, the fibers are projected to spinal cord via, reticular formation. So in decerebration the discharge, from neurons of area 4S cannot reach spinal motor, neurons. This leads to exaggeration of spinal motor, neurons resulting in rigidity., Decerebrate rigidity is also produced by stopping, the blood flow to the forebrain. It is done by occlusion of, the common carotid artery and the basilar artery at the, center of the pons., Opisthotonos, In decerebrate animal, the caricature or characteristic, posture is the extension of all the four limbs, extension, of the tail and arching of the back or hyperextension of, the spine. This type of attitude of the animal is called, opisthotonos. The animal can stand but, if disturbed, the, posture cannot be maintained., Decerebration in Man, In man, decerebration occurs due to lesion in dience, phalon or midbrain., , THALAMIC (MIDBRAIN) PREPARATION, In thalamic animal, all the connections of thalamus, with cerebral cortex are removed by sectioning at the, superior border of midbrain. All the fine sensations, such as fine touch, tactile discrimination and tactile, localization are lost. The conscious kinesthetic, sensation is also lost. But, the crude touch, pressure,, pain and temperature sensations remain intact., Righting reflexes are retained. The muscle tone is, not affected. Rigidity is absent. But when the animal, is held in air, extensor rigidity develops. Coordination, of the reflex movements is not lost. However, the, exaggeration of movements occurs during emotional, states. Abnormal involuntary movements are absent., , SPINAL PREPARATION, Complete transection of spinal cord is called spinal, preparation. Immediate effect of complete transection, of spinal cord is the spinal shock. The animal recovers, from the shock after some time. Tone is returned to, the flexor muscles. Extensor muscles do not regain the, tone or regain it after some time and these muscles, attain the flaccidity. It is because the facilitatory, impulses from reticular formation are cut off in spinal, preparation. Effects of complete transection of spinal, cord are given in Chapter 143.
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Chapter, , Proprioceptors, , 156, , PROPRIOCEPTORS, MUSCLE SPINDLE, , , , , STRUCTURE, NERVE SUPPLY, FUNCTIONS, , GOLGI TENDON ORGAN, , , , , STRUCTURE, NERVE SUPPLY, FUNCTIONS, , PACINIAN CORPUSCLE, FREE NERVE ENDING, , PROPRIOCEPTORS, It is necessary to know about the proprioceptors to, understand the maintenance of posture and equilibrium,, which is explained in the next chapter., , TABLE 156.1: Situation of proprioceptors, Proprioceptor, , Situation, , Muscle spindle, , Skeletal muscles, , Golgi tendon organ, , Tendons, , Proprioceptors are the receptors, which detect and, give response to movement and change in position of, different parts of the body. These receptors are also, called kinesthetic receptors., , Pacinian corpuscle, , Skin, Fascia over muscles, Tendons, Tissues around joint, Joint capsule, , Situation, , Free nerve ending, , Proprioceptors are situated in labyrinth, muscles,, tendon of the muscles, joints, ligaments and fascia, (Table 156.1)., , Skin, Skeletal muscles, Tendons, Fascia over muscles, Joints, , Labyrinthine proprioceptors, , Labyrinth, , Definition, , Different Proprioceptors, 1., 2., 3., 4., 5., , Muscle spindle, Golgi tendon organ, Pacinian corpuscle, Free nerve ending, Proprioceptors in labyrinth., Proprioceptors in the labyrinth are described in, Chapter 158., , MUSCLE SPINDLE, Muscle spindle is a spindle-shaped proprioceptor, situated in the skeletal muscle. It is formed by modified, skeletal muscle fibers called intrafusal muscle fibers., STRUCTURE OF MUSCLE SPINDLE, Muscle spindle has a central bulged portion and two, tapering ends. Each muscle spindle is formed by 5 to 12
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Chapter 156 t Proprioceptors 909, intrafusal muscle fibers. All these fibers are enclosed, , by a capsule, which is formed by connective tissue., Intrafusal fibers are attached to the capsule on either, end. The capsule is attached to either side of extrafusal, fibers or the tendon of the muscle. Thus, intrafusal fibers, are placed parallel to the extrafusal fibers. Intrafusal, fibers are thin and striated (Fig. 156.1)., Central portion of the intrafusal fibers does not, contract because it has only few or no actin and myosin, filaments. So, this portion acts only as a receptor., Only the end portion of intrafusal fibers can contract., The discharge from gamma motor neurons causes the, contraction of intrafusal fibers., Types of Intrafusal Fibers, Muscle spindle is formed by two types of intrafusal, fibers:, 1. Nuclear bag fiber, 2. Nuclear chain fiber., 1. Nuclear bag fiber, , NERVE SUPPLY TO MUSCLE SPINDLE, Muscle spindle is innervated by both sensory and motor, nerves. It is the only receptor in the body, which has, both sensory and motor nerve supply., Sensory Nerve Supply, Each muscle spindle receives two types of sensory, nerve fibers:, 1. Primary sensory nerve fiber, 2. Secondary sensory nerve fiber., 1. Primary sensory nerve fiber, Primary sensory nerve fiber belongs to type Iα (Aα), nerve fiber. Each sensory (afferent) nerve fiber has two, branches. One of the branches supplies the central, portion of nuclear bag fiber (Fig. 156.2). The other, branch ends in central portion of the nuclear chain, fiber. These branches end in the form of rings around, central portion of nuclear bag and nuclear chain fibers., Therefore, these nerve endings are called annulospiral, endings., , Central portion of this fiber is enlarged like a bag and, contains many nuclei. Hence, it is called the nuclear bag, fiber., 2. Nuclear chain fiber, In nuclear chain fiber, central portion is not bulged and, the nuclei are arranged in the center in the form of a, chain. Nuclear chain fiber is attached to the side of, end portion of nuclear bag fiber., , FIGURE 156.1: Muscle spindle, , FIGURE 156.2: Nerve supply to muscle spindle. Red = Afferent, (sensory) nerve fibers, Blue = Efferent (motor) nerve fibers., Letters in parenthesis indicate the type of nerve fibers.
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910 Section 10 t Nervous System, 2. Secondary sensory nerve fiber, , Muscle spindle as the receptor organ for stretch reflex, , Secondary sensory nerve fiber is a type II (Aβ) nerve, fiber. It innervates only the nuclear chain fiber and, ends near the end portion of nuclear chain fiber like, the petals of the flower. So, this nerve ending is called, , Stimulation of muscle spindle elicits the stretch reflex., Intrafusal muscle fibers are situated parallel to the, extrafusal muscle fibers and are attached to the tendon, of the muscle by means of capsule. So, stretching of the, muscle causes stretching of the muscle spindle also., This stimulates the muscle spindle and it discharges, the sensory impulses. These impulses are transmitted, via the primary and secondary sensory nerve fibers to, the alpha motor neurons in spinal cord. Alpha motor, neurons in turn send motor impulse to muscles through, their fibers and cause contraction of extrafusal fibers, (Fig. 156.3)., , flower spray ending., , Motor Nerve Supply, Motor (efferent) nerve fiber supplying the muscle, spindle belongs to gamma motor neuron (Aγ) type., Motor nerve supply to nuclear bag fiber, Gamma motor nerve fiber supplying the nuclear bag, fiber ends as motor end plate. This nerve ending is, called plate ending. Functionally, it is known as, dynamic gamma efferent (motor) nerve fiber., Motor nerve supply to nuclear chain fiber, Gamma motor nerve fiber supplying the nuclear chain, fiber divides into many branches, which form a network, called trail ending. Functionally, it is known as static, gamma efferent (motor) nerve fiber. Sometimes, it gives, a branch to nuclear bag fiber also., , Response of muscle spindle to stretch, When the muscle is stretched, primary sensory nerve, fibers from muscle spindle discharge impulses. This, response is of two types:, i. Dynamic response, ii. Static response., , FUNCTIONS OF MUSCLE SPINDLE, Muscle spindle gives response to change in the length, of the muscle. It detects how much the muscle is being, stretched and sends this information to central nervous, system (CNS) via sensory nerve fibers. The information, is processed in CNS to determine the position of, different parts of the body. By detecting the change in, length of the muscle, the spindle plays an important, role in preventing the overstretching of the muscles., Muscle spindle has two functions:, 1. It forms the receptor organ for stretch reflex, 2. It plays an important role in maintaining muscle, tone., 1. Role of Muscle Spindle in Stretch Reflex, Stretch reflex, Stretch reflex is the reflex contraction of muscle when, it is stretched. It is also called myotatic reflex. It is, a monosynaptic reflex and the quickest of all the, reflexes. Extensor muscles, particularly the antigravity, muscles exhibit a severe and prolonged contraction, during stretch reflex. Stretch reflex plays an important, role in maintaining posture., , FIGURE 156.3: Stretch reflex. 1. Afferent impulses from, muscle spindle of stretched muscle. 2. Efferent impulses from, α-motor neurons causing contraction of muscle.
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Chapter 156 t Proprioceptors 911, i. Dynamic response, Dynamic response is the response in which the primary, sensory nerve fibers discharge rapidly. When there is a, change in length of the muscle by stretching, primary, sensory nerve fibers from nuclear bag fiber start, discharging impulses very rapidly. But, the discharge, becomes less or nil during continuous stretching of the, muscle. Discharge of impulses start only if there is change, in degree of stretching of the muscle. Thus, the response, depends upon rate of change in length of the muscle., ii. Static response, Static response is the response in which impulses are, discharged rapidly and continuously throughout the, period of muscle stretch by primary sensory nerve fibers, of the nuclear chain fibers., Thus, the muscle spindle gives response to change, in length of the muscle as well as rate of change in, length., Physiologic tremor, Physiologic tremor is the continuous discharge of, actions potentials with low voltage and ineffective, frequency from primary and secondary sensory, nerve fibers of muscle spindle at resting condition., Physiological tremor plays an important role in the, feedback regulation of muscle length., 2. Role of Muscle Spindle in the Maintenance, of Muscle Tone, The state of continuous and partial contraction of the, muscle is called muscle tone (Chapter 157). It is due, to the continuous discharge of impulses from gamma, motor neurons., Gamma motor neurons innervate the intrafusal, fibers. Motor impulses from gamma motor neurons, stimulate the intrafusal fibers of muscle spindle,, which in turn sends sensory impulses back to spinal, cord. Now the alpha motor neurons in spinal cord are, activated resulting in contraction of extrafusal fibers of, muscle. Refer Chapter 157 for details of this process., When the frequency of discharge from gamma motor, neurons increases, activity of muscle spindle is, increased and the muscle tone also increases., , fibers. It is placed in series between the muscle fibers, and the tendon. Golgi tendon organ is formed by a, group of nerve endings covered by a connective tissue, capsule (Fig. 156.4)., NERVE SUPPLY TO GOLGI TENDON ORGAN, Sensory nerve fiber supplying the Golgi tendon organ, belongs to Ib type. The nerve fiber supplying Golgi, tendon organ ramifies into many branches. Each branch, ends in the form of a knob., FUNCTIONS OF GOLGI TENDON ORGAN, Golgi tendon organ gives response to the change in the, force or tension developed in the skeletal muscle during, contraction. It is also the receptor for inverse stretch, reflex and lengthening reaction and thereby prevents, damage of muscle due to overstretching., 1. Role of Golgi Tendon Organ, in Forceful Contraction, During powerful contraction, tension in the muscles, increases and stimulates Golgi tendon organ, which discharges the sensory impulses. Impulses are transmitted by Ib sensory nerve fiber to an inhibitory interneuron, in the spinal cord. Interneuron, in turn, causes, development of inhibitory postsynaptic potential, (IPSP) in motor neurons, which supply the muscle., Now, the contraction of the muscle is inhibited., 2. Role of Golgi Tendon Organ, in Inverse Stretch Reflex, Inverse stretch reflex, Inverse stretch reflex is the sudden decrease in resistance due to relaxation (instead of contraction) when a, , GOLGI TENDON ORGAN, STRUCTURE OF GOLGI TENDON ORGAN, Golgi tendon organ is situated in the tendon of, skeletal muscle near the attachment of extrafusal, , FIGURE 156.4: Golgi tendon apparatus
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912 Section 10 t Nervous System, muscle is stretched excessively. It is also called inverse, myotatic reflex and it is a polysynaptic reflex., Inverse stretch reflex is actually the inhibition of, contraction due to excessive stretching. So, it is also, called the autogenic inhibition., Mechanism of inverse stretch reflex, Excessive stretch of the muscle leads to activation of, Golgi tendon organ, which send afferent impulses which, cause:, i. Stimulation of inhibitory internuncial neuron,, which in turn inhibits alpha motor neuron of the, stretched muscle resulting in relaxation, ii. Stimulation of excitatory internuncial neuron,, which in turn activates alpha motor neuron of, the antagonistic muscle. It leads to contraction of, antagonistic muscle and relaxation of stretched, muscle., 3. Role of Golgi Tendon Organ in Lengthening, Reaction, When tension increases during muscular contraction, caused by stretch reflex, the Golgi tendon organ is, activated. It causes development of a spinal reaction,, which is called the lengthening reaction. It can be, demonstrated in a decerebrate preparation., In decerebrate rigidity, the extension of limbs is, due to spastic contraction of extensor muscles. It is, because of increased discharge from gamma motor, neurons, which facilitates the stretch reflex., , In a decerebrate animal, some resistance is, offered when the arm is flexed at elbow joint passively., That is, the arm cannot be flexed easily. This type, of resistance is offered because of the stretch reflex, developed in the triceps muscle. However, if forearm, is flexed forcefully, resistance to flexion is abolished, suddenly, leading to quick flexion of arm. It is called the, lengthening reaction., Lengthening reaction is due to the activation of, Golgi tendon organ. The sudden flexion of arm is called, the Phillipson reflex or clasp knife reflex., , PACINIAN CORPUSCLE, Pacinian corpuscle is a mechanoreceptor that senses, pressure and vibration. It is situated in the deeper layers, of skin. It is also situated in the tissues surrounding the, joints such as fascia over the muscle, tendons and joint, capsule. Pacinian corpuscles situated in these tissues, are responsible for determining the position of joints., Since pacinian corpuscle is a rapidly adapting, receptor (phasic receptor) it is very sensitive to quick, changes in the position of joints. So it is believed to, send information about joint movement to CNS., , FREE NERVE ENDING, Free nerve ending is the receptor for pain sensation situated in skin, muscles, tendon, fascia and joints. As it is, a slow adapting receptor (tonic receptor) it is maximally, stimulated at specific joint positions. So it is believed to, send information about joint position to CNS.
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Posture and Equilibrium, , Chapter, , 157, , DEFINITION, BASIC PHENOMENA OF POSTURE, , , , MUSCLE TONE, STRETCH REFLEX, , POSTURAL REFLEXES, , , , , CLASSIFICATION OF POSTURAL REFLEXES, STATIC REFLEXES, STATOKINETIC REFLEXES, , DEFINITION, Subconscious adjustment of tone in different muscles, in relation to every movement is known as the posture., Significance of posture is to make the movement smooth, and accurate and to maintain the line of gravity constant, or to keep the body in equilibrium with line of gravity., Posture is not an active movement. It is the passive, movement associated with redistribution of tone in, different groups of related muscles., , BASIC PHENOMENA OF POSTURE, Basic phenomena for maintenance of posture are, muscle tone and stretch reflex., MUSCLE TONE, Definition, Muscle tone is defined as the state of continuous and, passive partial contraction of muscle with certain vigor, and tension. It is also called tonus. It is also defined as, resistance offered by the muscle to stretch., Significance of Muscle Tone, Muscle tone plays an important role in maintenance of, posture. Change in muscle tone enables movement, of different parts of the body. Muscle tone is present, , in all the skeletal muscles. However, tone is more in, antigravity muscles such as extensors of lower limb,, trunk muscles and neck muscles., Development of Muscle Tone, Gamma motor neurons and muscle spindle are res, , ponsible for the development and maintenance of, muscle tone., Muscle tone is purely a reflex process. This reflex is, a spinal segmental reflex. It is developed by continual, synchronous discharge of motor impulses from the, gamma motor neurons present in the anterior gray, horn of the spinal cord (Figs. 157.1 and 157.2)., Sequence of events, 1. Impulses from the gamma motor neurons cause, contraction of end portions of intrafusal fibers, (stimulus), 2. This stretches and activates the central portion of, the intrafusal fibers, which initiates the reflex action, for development of muscle tone by discharging the, impulses, 3. Impulses from the central portion of intrafusal, fibers pass through primary sensory nerve fibers, (afferent fibers) and reach the anterior gray horn, of spinal cord, 4. These impulses stimulate the alpha motor neurons, in anterior gray horn (center)
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914 Section 10 t Nervous System, , FIGURE 157.2: Schematic diagram showing development of, muscle tone, , FIGURE 157.1: Development of muscle tone.1. Impulses from, γmotor neuron stimulate muscle spindle. 2. Afferent impulses, from muscle spindle to αmotor neuron. 3. Efferent impulses, from αmotor neuron produce contraction of extrafusal fibers, and develop muscle tone., , 5. Alpha motor neurons in turn, send impulses to, extrafusal fibers of the muscle through spinal nerve, fibers (efferent fibers), 6. These impulses produce partial contraction of the, muscle fibers resulting in development of muscle, tone (response)., When the frequency of discharge from gamma, motor neurons increases, the activity of muscle spindle, is increased and muscle tone also increases., Stimulation of gamma motor neurons increases the, muscle tone. Lesion in gamma motor neurons leads to, loss of tone in muscles., Regulation of Muscle Tone, Though the muscle tone is developed by discharges from, gamma motor neurons, it is maintained continuously, , and regulated by some supraspinal centers situated in, different parts of brain. Some of these centers increase, the muscle tone by sending facilitatory impulses while, other centers decrease the muscle tone by inhibitory, impulses., , Supraspinal facilitatory centers, Supraspinal centers, which increase the muscle tone:, 1. Motor area 4 in cerebral cortex, 2. Cerebellum, 3. Descending facilitatory reticular system, 4. Red nucleus, 5. Vestibular nucleus., Supraspinal inhibitory centers, Supraspinal centers, which decrease the muscle tone:, 1. Suppressor areas of cerebral cortex, 2. Basal ganglia, 3. Descending inhibitory reticular system., Role of motor area of cerebral cortex – coactivation, Motor area of cerebral cortex influences the activity, of lower motor neurons by sending motor impulses, through the pyramidal tract fibers. Motor impulses
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Chapter 157 t Posture and Equilibrium 915, from cerebral cortex stimulate both αmotor neurons, and γmotor neurons simultaneously. This type of, simultaneous stimulation is called coactivation. It is also, called α-γ coactivation. Stimulation of α-motor neurons, causes contraction of extrafusal fibers. Stimulation, of γ-motor neurons causes contraction of intrafusal, fibers, which leads to increase in muscle tone., , STATIC REFLEXES, Static reflexes are the postural reflexes that maintain, posture at rest. Static reflexes are of four types:, I. General static reflexes or righting reflexes, II. Local static reflexes or supporting reflexes, III. Segmental static reflexes, IV. Statotonic or attitudinal reflexes., , Role of cerebellum and basal ganglia, It is interesting to find that cerebellum and basal ganglia, influence the muscle tone without sending direct fibers, to γmotor neurons. These parts of brain influence the, muscle tone indirectly through brainstem centers., Role of brainstem centers, Brainstem centers which influence the γmotor neurons, are in reticular formation, red nucleus and vestibular, nucleus. These centers modulate the discharge from, γmotor neurons by receiving signals from cerebral, cortex, cerebellum and basal ganglia., Abnormalities, Refer Chapter 34 for details of abnormalities of muscle, tone., STRETCH REFLEX, Basic reflex involved in maintenance of posture is the, stretch reflex, which is described in detail in the previous, chapter., This reflex is normally present and serves particularly, to maintain the body in an upright position. Such reflexes, are, therefore more pronounced in extensor muscles., , POSTURAL REFLEXES, Postural reflexes are the reflexes which are responsible, for maintenance of posture. Afferent impulses for the, maintenance of posture arise from proprioceptors,, vestibular apparatus and retina of eye and reach the, centers in central nervous system (CNS). The centers,, which maintain the posture, are located at different, levels of CNS particularly cerebral cortex, cerebellum,, brainstem and spinal cord. These centers send motor, impulses to the different groups of skeletal muscles, so that appropriate movements occur to maintain the, posture., CLASSIFICATION OF POSTURAL REFLEXES, Postural reflexes are generally classified into two groups:, A. Static reflexes, B. Statokinetic reflexes., , I. General Static Reflexes or Righting Reflexes, General static reflexes are otherwise called righting, reflexes because these reflexes help to maintain an, upright position of the body. Righting reflexes help to, govern the orientation of the head in space, position, of the head in relation to the body and appropriate, adjustment of the limbs and eyes in relation to the, position of the head, so that upright position of the body, is maintained., When a cat, held with its back downwards, is, allowed to fall through the air, it lands upon its paws,, with the head and body assuming the normal attitude in, a flash. A fish resists any attempt to turn it from its normal, position and if it is placed in water upon its back, it flips, almost instantly into the normal swimming position. All, these actions occur because of the righting reflexes., Righting reflexes consist of a chain of reactions,, which occur one after another in an orderly sequence., Each reflex causes the development of the succeeding, one., Righting reflexes are divided into five types:, 1. Labyrinthine righting reflexes acting on the neck, muscles, 2. Neck righting reflexes acting on the body, 3. Body righting reflexes acting on the head, 4. Body righting reflexes acting on the body, 5. Optical righting reflexes., First four reflexes are easily demonstrated, on a thalamic animal or a normal animal, which is, blindfolded., 1. Labyrinthine righting reflexes acting, on the neck muscles, When a thalamic animal (rabbit) is suspended by, holding at the pelvic region, its head turns up, until it, assumes its normal position. It is because of reflexes, arising from labyrinth, the sensory organ concerned with, equilibrium of head, in regard to the position of the body., Turning the body of animal through air into different, positions is followed by compensatory movements, of the head. After extirpation of labyrinths, the head, shows no compensatory movements when the rabbit is, suspended. It hangs simply like that of a dead rabbit.
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916 Section 10 t Nervous System, 2. Neck righting reflexes acting on the body, It is noticed that during labyrinthine righting reflexes,, the head raises up to normal position. It is because of, the contraction of neck muscles. Now, the contraction of, neck muscles produces proprioceptive impulses, which, act on the body and rotate the body in relation to position, of head. This reflex is well noticed, if the animal is laid, down in resting position upon its side on a table., 3. Body righting reflexes acting on the head, Labyrinthine righting reflexes are not the only reflexes, acting on neck muscles to cause rotation of head. If the, animal is laid down upon its side on a table, the unequal, distribution of pressure on that particular side of the, body stimulates exteroceptors on the skin. Impulses, thus generated by exteroceptors, act on neck muscles, and rotate the head., 4. Body righting reflexes acting on the body, When the same animal is laid down on the table on, its side, with head held down to table, to eliminate, labyrinthine and neck righting reflexes, the body, attempts to right itself by raising the lower parts. It is, because of the impulses from exteroceptors on that, side of body acting on the body itself., 5. Optical righting reflexes, Optical righting reflexes are initiated through the retinal, impulses. Center for optical righting reflexes is in the, occipital lobe of cerebral cortex. So, these reflexes are, absent in thalamic animal. Optical righting reflexes help, to correct the position of the body or head with the help, of sight. It is proved in a labyrinthectomized animal., When such an animal is suspended, it rotates its, head to normal position with the help of sight. But, the, movements of head do not occur if eyes of the animal, are closed., Summary of righting reflexes, Following are the sequential events of righting reflexes:, i. When the animal is placed upon its back, labyrinthine, reflexes acting upon neck muscles turn the head, into its normal position in space, in relation to body, ii. Proprioceptive reflexes of neck muscles then bring, the body into its normal position in relation to position, of head, iii. When resting upon a rigid support, these reflexes, are reinforced by the body righting reflexes on the, head as well as on the body, iv. If the animal happens to be a labyrinthectomized, one, then it makes an attempt to recover its upright, , position as a result of operation of the optical righting, reaction. If the optical righting reflexes are abolished, by covering the eyes, the righting ability is lost., Optical righting reflexes are also demonstrated in 3, or 4 weeks old baby. When laid down on belly, i.e. prone, position, the baby tries to raise the head to a vertical, position., Centers for righting reflexes, Centers for the first four righting reflexes are in red, nucleus situated in midbrain. Center for optical righting, reflexes is in the occipital lobe of cerebral cortex (Table, 157.1)., , II. Local Static Reflexes or Supporting Reflexes, Local static reflexes or supporting reactions support the, body in different positions against gravity and also protect, the limbs against hyperextension or hyperflexion., Supporting reactions are classified into two types:, 1. Positive supporting reflexes, 2. Negative supporting reflexes., 1. Positive supporting reflexes, Positive supporting reflexes are the reactions, which, help to fix the joints and make the limbs rigid like pillars,, so that limbs can support the weight of the body against, gravity. It is brought about by the simultaneous reflex, contractions of both extensor and flexor muscles and, other opposing muscles. The impulses for these reflexes, arise from proprioceptors present in the muscles,, joints and tendons and the exteroceptors, particularly, pressure receptors present in deeper layers of the skin, of sole. While standing, the positive supporting reflexes, are developed in the following manner:, i. When an animal stands on its limbs, the pres, sure of the animal’s paw upon the ground pro, duces proprioceptive impulses from flexor and, extensor muscles of the limbs, particularly in, terminal segments of the limbs like digits, ankle, or wrist. The proprioceptive impulses cause, reflex contraction of the muscles of limbs making, the limbs rigid., ii. Excessive extension at the joints is checked or, guarded by the myotatic reflexes setting up in, the flexor muscles. When the flexor muscles are, simultaneously contracting, extensor muscles, cannot be stretched beyond the physiological, limits. Similarly, over activity of the flexor, muscles is prevented by the stretch reflexes, developed in the extensor muscles.
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Chapter 157 t Posture and Equilibrium 917, TABLE 157.1: Static postural reflexes, Reflex, , Center, , Animal preparation to, demonstrate, , 1. Labyrinthine righting reflexes acting on the, neck muscles, General static reflexes, (Righting reflexes), , 2. Neck righting reflexes acting on the body, 3. Body righting reflexes acting on the head, , Segmental static reflexes, Statotonic or attitudinal, reflexes, , Thalamic or normal, blindfolded animal, , Occipital lobe, , Labyrinthectomized, animal, , Spinal cord, , Decorticate animal, , Spinal cord, , Spinal animals, , Medulla oblongata, , Decerebrate animal, , 4. Body righting reflexes acting on the body, 5. Optical righting reflexes, , Local static reflexes, , Red nucleus situated, in midbrain, , 1. Positive supporting reflexes, 2. Negative supporting reflexes, Crossed extensor reflex, 1. Tonic labyrinthine and neck reflexes acting, on the limbs, 2. Labyrinthine and neck reflexes acting on, the eyes, , iii. Impulses arise even from exteroceptors while, standing, when the sole remains in contact, with the ground. It causes stimulation of the, pressure receptors, which are present in, deeper layers of the skin. These impulses from, pressure receptors reinforce the rigidity of the, limbs caused by the proprioceptive impulses., 2. Negative supporting reflexes, Relaxation of the muscles and unfixing of the joints, enable the limbs to flex and move to a new position., It is called negative supporting reaction. It is brought, about by raising the leg off the ground and plantar, flexion of toes and ankle. When the leg is lifted off, the ground, the exteroceptive impulses are stopped., When the toes and ankle joints are plantar flexed, the, stretch stimulus for the plantar muscles is stopped. So,, unlocking of the limbs occurs. Moreover, by the plantar, flexion of the toes and ankle, the dorsiflexor muscles, are stretched, causing relaxation of the extensors and, contraction of the flexors of the knee., The positive and negative supporting reactions, are demonstrated well on a decorticate animal. The, centers for the supporting reflexes are located in the, spinal cord., III. Segmental Static Reflexes, Segmental static reflexes are very essential for walking. During walking, in one leg, the flexors are active, and the extensors are inhibited. On the opposite leg,, , the flexors are inhibited and extensors are active., Thus, the flexors and extensors of the same limb are, not active simultaneously. It is known as crossed, extensor reflex. It is due to the reciprocal inhibition, and the neural mechanism responsible for this reflex, is called Sherrington reciprocal innervation. Refer, Chapter 142 for details., Segmental static reflexes are demonstrated in, spinal animal. And, the centers for these reflexes are, situated in the spinal cord., IV. Statotonic or Attitudinal Reflexes, Statotonic or attitudinal reflexes are developed accord, ing to the attitude of the body and are of two types:, 1. Tonic labyrinthine and neck reflexes acting on the, limbs, 2. Labyrinthine and neck reflexes acting on the eyes., 1. Tonic labyrinthine and neck reflexes, acting on the limbs, Tonic labyrinthine and neck reflexes decrease or, increase the tone of the skeletal muscles of the limbs, in accordance to the attitude or position of the head., These reflexes are best studied in decerebrate animal., The proprioceptors concerned with these reflexes are, in the labyrinthine apparatus. Whenever the position, of the head is altered, the receptors present in the, labyrinth are stimulated and generate impulses. The, impulses are also generated from the neck muscles, when the position of the head is altered. The impulses
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918 Section 10 t Nervous System, from labyrinth produce the same effect on all the four, limbs. But the impulses from neck muscles cause, opposite effects in the forelimbs and hind limbs., The labyrinthine reflexes are particularly effective, on extensor muscles. When the head is dorsiflexed, all, the four limbs are extended maximally and when the, head is ventriflexed, all the four limbs are flexed., In a labyrinthectomized animal where only neck, reflexes are operated, during dorsiflexion of the head,, there is extension of the forelimbs and flexion of the, hind limbs. The ventriflexion of the head causes flexion, of the forelimbs and extension of the hind limbs., The importance of these reflexes is understood, well, while observing the movements during change, in the attitude of a normal animal. When an animal, turns to one side, the limbs of that side become rigid in, order to support the weight of the body. A cat looking, upwards, keeps the hind limbs flexed but forelimbs, remain extended. It gives a suitable inclination to the, back of the animal, which improves the positions of the, head and eyes. When the cat looks down, forelimbs, are flexed and hind limbs are extended, giving the, proper supported inclination at the neck region., 2. Labyrinthine and neck reflexes acting, on the eyes, According to the changes in the position of the head, and neck, the eyes are also moved. These reflexes, , arise from labyrinth and neck muscles. Turning the head, downward causes upward movement of the eyes. The, eyes remain in this position as long as the position of, the head is retained., When the head is moved down, the tone in the, superior recti and inferior oblique are increased and, tone of inferior recti and superior oblique are reduced,, so that the eyeballs move upwards. When the head, is turned to one side, a corresponding compensatory, movement of the eyes occurs., When the head is turned to one side, the eyes, deviate outward or inward in relation to the head. The, eyes are moved in a direction opposite to that of the, head movement. It is because of external and internal, recti., Centers for statotonic reflexes are present in the, medulla oblongata., STATOKINETIC REFLEXES, Statokinetic reflexes are the postural reflexes that, maintain posture during movement. These reflexes, are concerned with both angular (rotatory) and linear, (progressive) movements. The vestibular apparatus, is responsible for these reflexes. So, it is essential to, study the structure and functions of vestibular apparatus, to understand the statokinetic reflexes. The details of, vestibular apparatus are described in Chapter 158.
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Vestibular Apparatus, , Chapter, , 158, , INTRODUCTION, LABYRINTH, , , , BONY LABYRINTH, MEMBRANOUS LABYRINTH, , FUNCTIONAL ANATOMY OF VESTIBULAR APPARATUS, , , , SEMICIRCULAR CANALS, OTOLITH ORGAN OR VESTIBULE, , RECEPTOR ORGAN OF VESTIBULAR APPARATUS, , , , CRISTA AMPULLARIS, MACULA, , NERVE SUPPLY TO VESTIBULAR APPARATUS, , , , FIRST ORDER NEURON, SECOND ORDER NEURON, , FUNCTIONS OF VESTIBULAR APPARATUS, , , , FUNCTIONS OF SEMICIRCULAR CANALS, FUNCTIONS OF OTOLITH ORGAN, , EFFECTS OF STIMULATION OF SEMICIRCULAR CANALS, , , , ROTATIONAL MOVEMENT, CALORIC STIMULATION, , APPLIED PHYSIOLOGY – EFFECT OF LABYRINTHECTOMY, , , , BILATERAL LABYRINTHECTOMY, UNILATERAL LABYRINTHECTOMY, , MOTION SICKNESS, , , , , , DEFINITION, CAUSE, SYMPTOMS, PREVENTION, , INTRODUCTION, Vestibular apparatus is the part of labyrinth or inner, ear. It plays an important role in maintaining posture, and equilibrium through statokinetic reflexes. Other, part of labyrinth is the cochlea, which is concerned with, , sensation of hearing., , LABYRINTH, Labyrinth (inner ear) consists of two structures:, , 1. Bony labyrinth, 2. Membranous labyrinth., BONY LABYRINTH, Bony labyrinth is a series of cavities or channels present in the petrous part of temporal bone. Membranous, labyrinth is situated inside bony labyrinth. The space, between bony labyrinth and membranous labyrinth is, filled with a fluid called perilymph or periotic fluid. This
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920 Section 10 t Nervous System, fluid is similar to ECF in composition with large amount, of sodium ions. Bony labyrinth encloses membranous, labyrinth (Fig. 158.1)., MEMBRANOUS LABYRINTH, Membranous labyrinth is formed by membranous, tubules and sacs. It consists of two portions:, 1. Cochlea, which is concerned with sensation of, hearing (Chapter 172), 2. Vestibular apparatus, which is concerned with, posture and equilibrium., Membranous labyrinth is filled with a fluid called, endolymph or otic fluid. Endolymph is similar to ICF in, composition. It has large quantity of potassium ions., , FUNCTIONAL ANATOMY OF, VESTIBULAR APPARATUS, Vestibular apparatus is formed by three semicircular, canals and otolith organ (vestibule)., SEMICIRCULAR CANALS, Semicircular canals are the tubular structures placed, at right angles to each other. Because of this type of, arrangement, semicircular canals represent the three, , axes of rotation, i.e. vertical, anteroposterior and transverse axes. Semicircular canals are named according, to the situation as follows:, 1. Anterior or superior canal, 2. Posterior canal, 3. Lateral or horizontal or external canal., Anterior and posterior canals are situated vertically, and the lateral canal is situated in horizontal plane, (Fig. 158.2)., When the head is tilted forward at an angle of 30°,, lateral canals of both the sides are at horizontal plane, parallel to earth with the convexities directed outward, and a little backward. Anterior canals are at vertical, plane and directed forward and outward at 45°. Posterior, canals are also at vertical plane, but directed backward, and outward at 45°., Therefore, the plane of position of anterior canal of, one side is parallel to the plane of posterior canal of, opposite side., Ampulla, There are two ends for each semicircular canal. One, end is narrow and the other end is enlarged. The, enlarged end is called ampulla. Ampulla contains the, receptor organ of semicircular canals known as crista, ampullaris. Ampulla of all the three canals and narrow, end of horizontal canal open directly into the utricle. The, narrow ends of anterior and posterior canals open into, utricle jointly, by forming the common crus. Thus, all the, three semicircular canals open into utricle by means of, five openings. Utricle opens into saccule., OTOLITH ORGAN OR VESTIBULE, Otolith organ or vestibule is formed by utricle and saccule. Often utricle and saccule are together called, otoliths. Utricle communicates with saccule through, utriculosaccular duct. Saccule communicates with, cochlear duct through ductus reuniens. Another duct, called endolymphatic duct arises from utriculosaccular, duct. It ends in a bag-like structure called endolymphatic, sac, which lies on the cranial surface of petrous bone., , RECEPTOR ORGAN IN, VESTIBULAR APPARATUS, , FIGURE 158.1: Labyrinth, , Receptor organ in semicircular canal is called crista, ampullaris and that in otolith organ is called macula., These receptor organs contain the proprioceptors.
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Chapter 158 t Vestibular Apparatus 921, , FIGURE 158.2: Position of semicircular canals when the head is tilted at 30°, , RECEPTOR ORGAN IN SEMICIRCULAR, CANAL – CRISTA AMPULLARIS, Crista ampullaris is a crest-like structure situated, inside the ampulla of semicircular canals. The crest, is formed by a receptor epithelium (neuroepithelium),, which consists of hair cells, supporting cells and, secreting epithelial cells. The secreting epithelial cells, secrete the ground substance, proteoglycan. These, cells are arranged in planum semilunatum (group of, epithelial cells) around hair cells (Fig. 158.3)., Hair Cells, , stereocilia. Each stereocilium is attached at its tip to, the neighboring taller one by means of a fine process, called tip link. Because of the tip links, all the stereocilia, are held together. One of the cilia is very tall, which is, named as kinocilium (Fig. 158.4)., , Cupula, From crista ampullaris, a dome-shaped gelatinous, structure extends up to the roof of the ampulla. It is, known as cupula. Cilia of hair cells are projected into, cupula., , Hair cells are the receptor cells (proprioceptors) of, crista ampullaris. There are two types of hair cells, type, I and type II hair cells. Hair cells of semicircular canals,, utricle and saccule receive both afferent and efferent, nerve terminals., Type I hair cells, Type I hair cells are flask shaped. Afferent nerve, terminates in the form of a calyx that surrounds the, cell body. Efferent nerve terminal ends on the surface, of calyx., Type II hair cells, These cells have a cylindrical or test tube shape. Both, afferent and efferent nerve fibers terminate on the, surface cell body without forming calyx., Cilia of hair cells, Apex of each hair cell has a cuticular plate. From, this plate, about 40 to 60 cilia arise, which are called, , FIGURE 158.3: Crista ampullaris
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922 Section 10 t Nervous System, , NERVE SUPPLY TO, VESTIBULAR APPARATUS, Impulses from the hair cells of crista ampullaris and, maculae are transmitted to medulla oblongata and, other parts of central nervous system (CNS) through, the fibers of vestibular division of vestibulocochlear, (VIII cranial) nerve., FIRST ORDER NEURON, , FIGURE 158.4: Hair cells of vestibular apparatus, , RECEPTOR ORGAN IN OTOLITH, ORGAN – MACULA, Receptor organ in otolith organ is called macula. Like, crista ampullaris, macula is also formed by neuroepithelium and supporting cells. Neuroepithelium of, macula also has two types of hair cells, the type I and, type II hair cells (Fig. 158.5)., Otolith Membrane, Like crista ampullaris, macula is also covered by a, gelatinous membrane called otolith membrane. It, is a flat structure and not dome shaped like cupula., The stereocilia and kinocelium of each hair cell are, embedded in otolith membrane. Otolith membrane, contains some crystals, which are called ear dust,, otoconia or statoconia. Otoconia are mainly constituted, by calcium carbonate., Situation of Macula, , First order neurons of the sensory pathway are bipolar, in nature. The soma of bipolar cells is present in, vestibular or Scarpa ganglion, which is situated in the, internal auditory meatus. Dendrites of bipolar cells reach, the receptor organs, i.e. crista ampullaris and maculae, in vestibular apparatus. Branches of the dendrites have, close contact with basal part of hair cells. Dendrites, terminating on type I hair cells are comparatively larger, than those ending on type II hair cells., Axons of the first order neurons (bipolar cells) form, vestibular division of vestibulocochlear nerve. These, fibers reach the medulla oblongata and terminate in, vestibular nuclei. These nerve fibers are called primary, vestibular fibers., Vestibular Nuclei, There are four vestibular nuclei in the medulla, oblongata, viz. superior, inferior, lateral and medial, nuclei. Most of the primary vestibular fibers reaching, superior and medial nuclei come from crista ampullaris of semicircular canals. Lateral vestibular nucleus, receives fibers mainly from maculae of otolith organ, and inferior vestibular nucleus receives fibers from, both crista ampullaris and maculae., Efferent nerve fibers to hair cells, Some neurons in vestibular nuclei send efferent fibers,, which run back to the hair cells along with primary, vestibular fibers (see above). It is believed that these, efferent fibers to hair cells provide tonic inhibition of hair, cells., , Situation of macula is different in utricle and saccule., , Fibers to Cerebellum, , Macula in utricle, , Fibers from some bipolar cells reach cerebellum directly, and terminate in flocculonodular lobe or the fastigial, nucleus in cerebellum., , In utricle, the macula is situated in horizontal plane, so, that the cilia from hair cells are in vertical direction., Macula in saccule, , SECOND ORDER NEURON, , In the case of saccule, macula is in vertical plane and, the cilia are in horizontal direction., , Second order neurons of this pathway are located in, the four vestibular nuclei. Axons from vestibular nuclei
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Chapter 158 t Vestibular Apparatus 923, , FIGURE 158.5: Macula in otolith organ, , form the secondary vestibular fibers. Secondary, vestibular fibers form four tracts:, 1. Vestibulo-ocular tract, 2. Vestibulospinal tract, 3. Vestibuloreticular tract, 4. Vestibulocerebellar tract., 1. Vestibulo-ocular Tract, Fibers from superior, medial and inferior vestibular, nuclei descend downwards for short distance along, with vestibulospinal tract. Afterwards, these fibers, ascend through the medial longitudinal fasciculus, and terminate in the nuclei of III, IV and VI cranial, nerves, thus forming vestibulo-ocular tract. This tract, is concerned with movements of eyeballs in relation, to the position of the head., 2. Vestibulospinal Tract, Fibers from lateral nucleus descend downwards and, form the vestibulospinal tract. Some fibers from this, nucleus ascend upward and join medial longitudinal, fasciculus. Fibers of vestibulospinal tract are involved, in reflex movements of head and body during postural, changes., 3. Vestibuloreticular Tract, Some fibers from vestibular nuclei reach the reticular, formation of brainstem forming reticulospinal tract., , These fibers are concerned with the facilitation of, muscle tone., , 4. Vestibulocerebellar Tract, Some fibers arising from all four vestibular nuclei form, vestibulocerebellar tract and terminate in flocculonodular lobe and fastigial nuclei of cerebellum. This tract, is involved in coordination of movements according to, body position., , FUNCTIONS OF, VESTIBULAR APPARATUS, Receptors of semicircular canals give response, to rotatory movements or angular acceleration of, the head. And receptors of utricle and saccule give, response to linear acceleration of head., Thus, the vestibular apparatus is responsible, for detecting the position of head during different, movements. It also causes reflex adjustments in the, position of eyeball, head and body during postural, changes., FUNCTIONS OF SEMICIRCULAR CANALS, Semicircular canals are concerned with angular (rotatory) acceleration. Semicircular canals sense the rotational movement. Each semicircular canal is sensitive to, rotation in a particular plane.
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924 Section 10 t Nervous System, Superior Semicircular Canal, Superior semicircular canal gives response to rotation, in anteroposterior plane (transverse axis), i.e. front to, back movements like nodding the head while saying, ‘yes – yes’., Horizontal Semicircular Canal, Horizontal semicircular canal gives response to rotation, in horizontal plane (vertical axis), i.e. side to side, movements (left to right or right to left) like shaking the, head while saying ‘no – no’., Posterior Semicircular Canal, Posterior semicircular canal gives response to rotation, in the vertical plane (anteroposterior axis) by which, head is rotated from shoulder to shoulder., Mechanism of Stimulation of Receptor, Cells in Semicircular Canal, At the beginning of rotation, receptor cells are, stimulated by movement of endolymph inside the, semicircular canals. However, receptors are stimulated, only at the beginning and at the stoppage of rotatory, movements. And during rotation at a constant speed,, these receptors are not stimulated., When a person rotates in clockwise direction in, horizontal plane (vertical axis), horizontal canal moves, in clockwise direction. But there is no corresponding, movement of endolymph inside the canal at the beginning of rotation. Because of the inertia, endolymph, remains static. This phenomenon causes relative displacement of endolymph in the direction opposite to that, of the rotation of head. That is, the fluid is pushed in, anticlockwise direction., Thus, in the right horizontal semicircular canal,, the endolymph flows towards the ampulla and in the, left canal, the fluid moves away from the ampulla (Fig., 158.6)., Movement of endolymph in semicircular canal, in, turn causes corresponding movement of gelatinous, cupula. Thus, in the right horizontal canal, the cupula, moves towards the ampulla. Whereas in left canal cupula, moves away from ampulla. In any semicircular canal,, when cupula moves towards the ampulla, stereocilia, of hair cells are pushed towards kinocilium leading to, stimulation of hair cells. When cupula moves away, from ampulla, the stereocilia are pushed away from, kinocilium and hair cells are not stimulated., Thus, at the commencement of rotation in clockwise, direction around vertical axis, hair cells at ampulla of, , FIGURE 158.6: Movement of fluid and excitation of crista, ampullaris in right horizontal semicircular canal during clockwise rotation., , horizontal canal in right ear are stimulated. But, the hair, cells in horizontal canal of left ear are not stimulated., Because of stimulation, the hair cells in right horizontal canal send information (impulses) through, sensory nerve fibers to vestibular, cerebellar and reticular centers. Now, these centers send proper instructions, to various muscles of the body to maintain equilibrium, of the body during angular acceleration (rotation)., On the other hand, rotation in anticlockwise, direction causes stimulation of hair cells in ampulla of, horizontal canal in left ear only. Hair cells of horizontal, canal in right ear are not stimulated. Stimulation of hair, cells in left ear is followed by the process as in the case, of clockwise rotation., Electrical Potential in Hair Cells –, Mechanotransduction, Mechanotransduction is a type of sensory transduction (Chapter 139) in the hair cell (receptor) by, which the mechanical energy (movement of cilia in, hair cell) caused by stimulus is converted into action, potentials in the vestibular nerve fiber., Resting membrane potential in hair cells is –60, mV. Movement of stereocilia of hair cells towards, kinocilium causes opening of mechanically gated, potassium channels (Chapter 3). It is followed by influx, of potassium ions from endolymph which contains, large amount of potassium ions. Potassium ions cause
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Chapter 158 t Vestibular Apparatus 925, development of mild depolarization in hair cells up to, –50 mV. This type of depolarization is called receptor, potential. Besides potassium ions, calcium ions also, enter the hair cells from endolymph., Receptor potential in hair cells is non-propagative., But, it causes generation of action potential in nerve, fibers distributed to hair cells. Depolarization of hair, cells causes them to release a neurotransmitter, which, generates the action potential in the nerve fibers. It is, believed that the probable neurotransmitter may be, glutamate., Movement of stereocilia in the opposite direction, (away from kinocilium) causes hyperpolarization of, hair cells. Calcium may play a role in the development, of hyperpolarization. Hyperpolarization in hair cells, stops generation of action potential in the nerve fibers, (Fig. 158.7)., Adaptation of Receptors in Semicircular, Canal during Rotation, Hair cells of crista ampullaris generate impulses even, at rest. But, the frequency of discharge is very low at, resting conditions. It is about 50 to 100 impulses per, minute., At the commencement of rotation, discharge of, impulses reaches a higher frequency of 600 to 800 per, minute, depending upon the speed of rotation. However,, the rapid discharge of impulses lasts only for the first 20, to 25 seconds of rotation. Afterwards, even if rotation, continues, the frequency of impulses falls back to the, resting level. It is because of the adaptation of receptors, during continuous rotation., Cause for adaptation of receptor cells, At the onset of rotation, endolymph inside the semicircular canal does not move along with semicircular, canal because of inertia of the fluid. So semicircular, canal moves leaving the endolymph behind, which is like, moving in the opposite direction. Now the endolymph, is pushed into ampulla towards the utricle. It causes, stimulation of hair cells but, after about 20 seconds, due to the accumulation of endolymph, a pressure, is developed in ampulla. Due to the back pressure,, endolymph starts moving away from ampulla, i.e. it, starts moving along with semicircular canal at the same, speed. It causes adaptation of the hair cells., Hair cells of crista ampullaris of vertical semicircular canals are stimulated during the rotation of, head in anteroposterior or transverse axis. However,, the mechanism involved is similar to that of the hair, cells of crista ampullaris of horizontal canals., , FIGURE 158.7: Mechanotransduction in hair cell of vestibular, apparatus. During activation, receptor potential develops in, hair cell due to the influx of potassium and calcium ions., Receptor potential causes release of neurotransmitter from, hair cell, which induces development of action potential in, the afferent nerve fiber., , Nystagmus, Nystagmus is the rhythmic oscillatory involuntary movements of eyeball. It is common during rotation. It is due, to the natural stimulatory effect of vestibular apparatus, during rotational acceleration. Nystagmus occurs both, in physiological and pathological conditions., Vestibulo-ocular reflex and nystagmus, Nystagmus is a reflex phenomenon that occurs in order, to maintain the visual fixation. Since the movements of, eyeballs occur in response to stimulation of vestibular, apparatus this reflex is called vestibulo-ocular reflex., Movement of eyeball during nystagmus, Nystagmus has two components of movement, which, occur alternately:, 1. Slow component, 2. Quick component.
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926 Section 10 t Nervous System, 1. Slow component, , FUNCTION OF OTOLITH ORGAN, , At the beginning of rotation, since eyes are fixed at, a particular object (point), eyeballs rotate slowly in, the direction opposite to that of rotation of the head., It is called slow component of nystagmus. It is due, to vestibulo-ocular reflex. This reflex is because of, labyrinthine impulses reaching the ocular muscles via, vestibular nuclei and III, IV and V cranial nerves., , Otolith organ is concerned with linear acceleration and, detects acceleration in both horizontal and vertical, planes. Utricle responds during horizontal acceleration, and saccule responds during vertical acceleration., , 2. Quick component, When the slow movement of eyeballs is limited, the, eyeballs move to a new fixation point in the direction of, rotation of head. This movement to a new fixation point, occurs with a jerk. So, it is called the quick component., Quick component of nystagmus is due to the activation, of some centers in brainstem., Postrotatory nystagmus, Nystagmus that occurs immediately after stoppage of, rotation is called postrotatory nystagmus. It is due to, movement of cupula in opposite direction caused by, the endolymph, when rotation is stopped. Postrotatory, nystagmus can be demonstrated by Barany chair (see, below for details)., Postrotatory Reactions, After the end of rotatory movement, two reactions, occur:, 1. Feeling of rotation in opposite direction, 2. Postrotatory nystagmus., 1. Feeling of rotation in the opposite direction, When rotation in clockwise direction is stopped suddenly, endolymph moves in the direction of rotation in right, horizontal semicircular canal although the semicircular, canal stops moving. So, cupula moves away from, utricle., However, in the case of left horizontal semicircular, canal, endolymph moves into ampulla. There, it pushes, cupula towards the utricle and stimulates the hair cells, in crista of left canal. It causes feeling of rotation in, opposite direction when the rotation is stopped., 2. Postrotatory nystagmus, , Function of Utricle, Position of hair cells of macula helps utricle to respond, to horizontal acceleration. In utricle, the macula is, situated in horizontal plane with the hair cells in vertical, plane (Fig. 158.5). While moving horizontally, because, of inertia the otoconia move in opposite direction and, pull the cilia of hair cells resulting in stimulation of hair, cells., For example, when the body moves forward, the, otoconia fall back in otolith membrane and pull the cilia, of hair cells backward. Pulling of cilia causes stimulation, of hair cells. Hair cells send information (impulses), to vestibular, cerebellar and reticular centers. These, centers in turn send instructions to various muscles, to maintain equilibrium of the body during the forward, movement., Function of Saccule, Macula of saccule is situated in vertical plane with, the cilia of hair cells in horizontal plane. While moving, vertically, as in the case of utricle, otoconia of saccule, move in opposite direction and pull the cilia resulting in, stimulation of hair cells., For example, while climbing up, the otoconia move, down by pulling the cilia downwards. It stimulates, the hair cells, which in turn send information to the, brain centers. And the action follows as in the case of, movement in horizontal plane., Role of Otolith Organ in Resting Position, During resting conditions (in the absence of head, movement), hair cells are stimulated continuously, because of the pulling of otoconia by gravitational force., Stimulation of hair cells produces reflex movements, of head and limbs for the maintenance of posture, in relation to gravity. Because of this function, the, receptors of otolith organ are called gravity receptors., , It is already explained above., Nystagmus in Pathological Conditions, , EFFECTS OF STIMULATION OF, SEMICIRCULAR CANALS, , Nystagmus is very common in lesions of cerebellum, and lesions of brainstem involving vestibular nuclei or, vestibular nerve. It also occurs due to the damage of, labyrinth., , Under experimental conditions, semicircular canals can, be stimulated by two methods:, A. Rotational movement, B. Caloric stimulation.
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Chapter 158 t Vestibular Apparatus 927, ROTATIONAL MOVEMENT, , Effects of Caloric Stimulation, , Semicircular canal can be stimulated by rotational, movement with the help of Barany chair., , Stimulation of semicircular canals by thermal stimulus, develops nystagmus, vertigo and nausea. During the, treatment for ear infection, temperature of fluid instilled, into the ear must be equal to body temperature, so that,, such symptoms of caloric stimulation are avoided., , Barany Chair, Barany chair is a revolving chair. The subject is seated, on this chair with the head tilted forward at 30°. Both the, eyes are closed. The chair is rotated at a speed of 30, RPM for about 20 seconds and then stopped., Effects of Stimulation of Semicircular, Canals by Rotation, Stimulation of semicircular canals during rotation, in Barany chair produces some effects both during, rotation and after the end of rotation., Postrotatory Reactions, Twenty seconds after the stoppage of rotation in, Barany chair, following reactions occur:, 1. Postrotatory nystagmus: Eyes are closed during, rotation by Barany chair. When eyes are opened, after the sudden stoppage of rotation, nystagmus, starts. Postrotatory nystagmus exists for about 30, seconds., 2. Dizziness: Immediately after stoppage of rotation,, there is a feeling of unsteadiness. It is called the, dizziness. Dizziness is associated with feeling of, rotation in the opposite direction., 3. Vertigo: After the end of rotation, there is a feeling of, environment whirling around or, there is a feeling of, rotation of the person himself., 4. Other effects: Rotation for a longer period causes, nausea and vomiting. Blood pressure falls by about, 10 to 15 mm Hg. And, heart rate is reduced by 10 to, 12 beats per minute., , APPLIED PHYSIOLOGY – EFFECT, OF LABYRINTHECTOMY, BILATERAL LABYRINTHECTOMY, Removal of labyrinthine apparatus on both sides leads, to complete loss of equilibrium., Equilibrium could be maintained only by visual sensation. Postural reflexes are severely affected. There is, loss of hearing sensation too., UNILATERAL LABYRINTHECTOMY, Removal of labyrinthine apparatus on one side causes, less effect on postural reflexes. However, severe, autonomic symptoms occur. Autonomic symptoms are, due to unbalanced generation of impulses from the, unaffected labyrinthine apparatus., Symptoms are nausea, vomiting and diarrhea. During movement, the symptoms become very severe., The unaffected labyrinthine apparatus starts compensating the loss of functions of affected labyrinth., Hence, the symptoms disappear slowly after a few, months., , MOTION SICKNESS, DEFINITION, , If Barany chair is rotated with opened eyes, nystagmus, occurs continuously throughout the period of rotation., , Motion sickness is defined as the syndrome of physiological response during movement (travel) to which, the person is not adapted. It can occur while traveling, in any form of vehicle like automobile, ship, aircraft or, spaceship. Motion sickness that occurs while traveling, in a watercraft is called seasickness., , CALORIC STIMULATION, , CAUSE, , Semicircular canals can be stimulated bypassing, hot or cold water into the ear by using a syringe. The, transmission of change in temperature into labyrinth, alters the specific gravity of endolymph. This in turn, causes movement of cupula and stimulation of receptor, cells., , Motion sickness is due to excessive and repeated stimulation of vestibular apparatus. Excessive and repeated, stimulation of vestibular apparatus occurs because of:, 1. Rapid and repeated change in rate of motion while, traveling, 2. Rapid and repeated change in direction., , Reaction during Rotation with Opened Eyes
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928 Section 10 t Nervous System, Psychological factors such as anxiety about the, unfamiliar modes of travel may be added up to cause, motion sickness., SYMPTOMS, 1., 2., 3., 4., 5., 6., 7., , Nausea, Vomiting, Sweating, Diarrhea, Pallor (paleness), Excess salivation, Discomfort, , 8. Headache, 9. Disorientation., PREVENTION, Responses of motion sickness can be prevented by, avoiding greasy and bulky food before travel and by, taking antiemetic drugs (drugs preventing nausea, and vomiting). In experimental animals, motion sickness is abolished by bilateral removal of vestibular, apparatus, sectioning of vestibular nerve or ablation of, flocculonodular lobe.
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Electroencephalogram (EEG), , , , , , , Chapter, , 159, , INTRODUCTION, SIGNIFICANCE OF EEG, METHOD OF RECORDING EEG, WAVES OF EEG, EEG DURING SLEEP, , INTRODUCTION, Electroencephalography is the study of electrical act, , ivities of brain. Electroencephalogram (EEG) is the, graphical recording of electrical activities of brain., Electrical activity of the brain is complicated when, compared to that of a single nerve fiber or neuron. It is, due to the involvement of large number of neurons and, synapses., German psychiatrist Hans Berger was the first one, to analyze the EEG waves systematically and hence, the EEG waves are referred as Berger waves., , SIGNIFICANCE OF EEG, Electroencephalogram is useful in the diagnosis of, neurological disorders and sleep disorders. EEG pat, tern is altered in the following neurological disorders:, 1. Epilepsy, which occurs due to excessive discharge, of impulses from cerebral cortex, 2. Disorders of midbrain affecting ascending reticular, activating system, 3. Subdural hematoma during which there is collec, tion of blood in subdural space over the cerebral, cortex., , METHOD OF RECORDING EEG, Electroencephalograph is the instrument used to, record EEG. The electrodes called scalp electrodes, , from the instrument are placed over unopened skull or, over the brain after opening the skull or by piercing into, brain. Electrodes are of two types, unipolar and bipolar, , electrodes. While using bipolar electrodes, both the, terminals are placed in different parts of brain., When unipolar electrodes are used, the active, electrode is placed over cortex and the indifferent, electrode is kept on some part of the body away from, cortex., , WAVES OF EEG, Electrical activity recorded by EEG may have synchroni, zed or desynchronized waves. Synchronized waves, are the regular and invariant waves, whereas desynchronized waves are irregular and variant. In normal, persons, EEG has three frequency bands (Fig. 159.1):, 1. Alpha rhythm, 2. Beta rhythm, 3. Delta rhythm., In addition to these three types of waves, EEG in, children shows theta waves., ALPHA RHYTHM, Alpha rhythm consists of rhythmical waves, which, appear at a frequency of 8 to 12 waves/second with, the amplitude of 50 µV. Alpha waves are synchronized, waves., , Alpha rhythm is obtained in inattentive brain or, mind as in drowsiness, light sleep or narcosis with, closed eyes. It is abolished by visual stimuli or any other, type of stimuli or by mental effort. So, it is diminished, when eyes are opened.
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930 Section 10 t Nervous System, , FIGURE 159.1: Waves of electroencephalogram, , Waves of alpha rhythm are most marked in parieto, occipital area. Sometimes these waves appear in, other areas also., Alpha Block, , appear. Some controversy exists in naming such, waves. Often very high frequency waves are called, gamma rhythm. However, many scientists consider, these waves as beta rhythm., DELTA RHYTHM, , Alpha block is the replacement of synchronized alpha, waves in EEG by desynchronized and low voltage, waves when the eyes are opened. The desynchronized, waves do not have specific frequency. It occurs due to, any form of sensory stimulation or mental concentration,, such as solving arithmetic problems., Desynchronization is the common term used for, replacement of regular alpha waves with irregular low, voltage waves. It is due to the loss of synchronized, activity in neural elements that are responsible for, regular wave pattern., , Delta rhythm includes waves with low frequency and, high amplitude. These waves have the frequency of 1, to 5 per second with the amplitude of 20 to 200 µV. It, is common in early childhood during waking hours. In, adults, it appears mostly during deep sleep., Presence of delta waves in adults during conditions, other than sleep indicates the pathological process, in brain like tumor, epilepsy, increased intracranial, pressure and mental deficiency or depression. These, waves are not affected by opening the eyes., , BETA RHYTHM, , THETA WAVES, , Beta rhythm includes high frequency waves of 15 to 60, per second but, the amplitude is low, i.e. 5 to 10 µV., Beta waves are desynchronized waves. Beta rhythm, is recorded during mental activity or mental tension or, arousal state. It is not affected by opening the eyes., During higher mental activity or peak performance, state like conscious activity, problem solving and fear,, very high frequency waves of 30 to 100 per second, , Theta waves are obtained generally in children below 5, years of age. These waves are of low frequency and low, voltage waves. Frequency of theta waves is 4 to 8 per, second and the amplitude is about 10 µV., , EEG DURING SLEEP, Changes in the EEG pattern during sleep are described, in Chapter 160.
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Physiology of Sleep, , , , , , , , , Chapter, , 160, , DEFINITION, SLEEP REQUIREMENT, PHYSIOLOGICAL CHANGES DURING SLEEP, TYPES OF SLEEP, STAGES OF SLEEP AND EEG PATTERN, MECHANISM OF SLEEP, APPLIED PHYSIOLOGY – SLEEP DISORDERS, , DEFINITION, , 2. CARDIOVASCULAR SYSTEM, , Sleep is the natural periodic state of rest for mind, and body with closed eyes characterized by partial or, complete loss of consciousness. Loss of consciousness, leads to decreased response to external stimuli and, decreased body movements. Depth of sleep is not, constant throughout the sleeping period. It varies in, different stages of sleep., , Heart Rate, , SLEEP REQUIREMENT, Sleep requirement is not constant. However, average, sleep requirement per day at different age groups is:, 1. Newborn infants : 18 to 20 hours, 2. Growing children : 12 to 14 hours, 3. Adults, : 7 to 9 hours, 4. Old persons, : 5 to 7 hours., , PHYSIOLOGICAL CHANGES, DURING SLEEP, During sleep, most of the body functions are reduced, to basal level. Following are important changes in the, body during sleep:, 1. PLASMA VOLUME, Plasma volume decreases by about 10% during sleep., , During sleep, the heart rate reduces. It varies between, 45 and 60 beats per minute., Blood Pressure, Systolic pressure falls to about 90 to 110 mm Hg., Lowest level is reached about 4th hour of sleep and, remains at this level till a short time before waking, up. Then, the pressure commences to rise. If sleep is, disturbed by exciting dreams, the pressure is elevated, above 130 mm Hg., 3. RESPIRATORY SYSTEM, Rate and force of respiration are decreased. Respiration becomes irregular and Cheyne-Stokes type of, periodic breathing may develop., 4. GASTROINTESTINAL TRACT, Salivary secretion decreases during sleep. Gastric, secretion is not altered or may be increased slightly., Contraction of empty stomach is more vigorous., 5. EXCRETORY SYSTEM, Formation of urine decreases and specific gravity of, urine increases.
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932 Section 10 t Nervous System, 6. SWEAT SECRETION, , doxical sleep. It occupies about 20% to 30% of sleep-, , ing period. Functionally, REM sleep is very important, because, it plays an important role in consolidation of, memory. Dreams occur during this period., , Sweat secretion increases during sleep., 7. LACRIMAL SECRETION, , 2. NON-RAPID EYE MOVEMENT SLEEP –, NREM OR NON-REM SLEEP, , Lacrimal secretion decreases during sleep., 8. MUSCLE TONE, , Non-rapid eye movement (NREM) sleep is the type of, sleep without the movements of eyeballs. It is also called, slow-wave sleep. Dreams do not occur in this type of, sleep and it occupies about 70% to 80% of total sleeping period. Non-REM sleep is followed by REM sleep., Differences between the two types of sleep are, given in Table 160.1., , Tone in all the muscles of body except ocular muscles, decreases very much during sleep. It is called sleep, paralysis., 9. REFLEXES, Certain reflexes particularly knee jerk, are abolished., Babinski sign becomes positive during deep sleep., Threshold for most of the reflexes increases. Pupils are, constricted. Light reflex is retained. Eyeballs move up, and down., , STAGES OF SLEEP AND EEG PATTERN, RAPID EYE MOVEMENT SLEEP, During REM sleep, electroencephalogram (EEG), shows irregular waves with high frequency and low, amplitude. These waves are desynchronized waves., , 10. BRAIN, Brain is not inactive during sleep. There is a characteristic cycle of brain wave activity during sleep with, irregular intervals of dreams. Electrical activity in the, brain varies with stages of sleep (see below)., , NON-RAPID EYE MOVEMENT SLEEP, The NREM sleep is divided into four stages, based on, the EEG pattern. During the stage of wakefulness, i.e., while lying down with closed eyes and relaxed mind, the, alpha waves of EEG appear. When the person proceeds, to drowsy state, the alpha waves diminish (Fig. 160.1)., , TYPES OF SLEEP, Sleep is of two types:, 1. Rapid eye movement sleep or REM sleep, 2. Non-rapid eye movement sleep, NREM sleep or, non-REM sleep., , Stage I: Stage of Drowsiness, Alpha waves are diminished and abolished. EEG, shows only low voltage fluctuations and infrequent, , 1. RAPID EYE MOVEMENT SLEEP –, REM SLEEP, , delta waves., , Stage II: Stage of Light Sleep, , Rapid eye movement sleep is the type of sleep, associated with rapid conjugate movements of the, eyeballs, which occurs frequently. Though the eyeballs, move, the sleep is deep. So, it is also called para-, , Stage II is characterized by spindle bursts at a frequency of 14 per second, superimposed by low voltage, delta waves., , TABLE 160.1: Rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep, Characteristics, , REM sleep, , Non-REM sleep, , 1. Rapid eye movement (REM), , Present, , Absent, , 2. Dreams, , Present, , Absent, , 3. Muscle twitching, , Present, , Absent, , 4. Heart rate, , Fluctuating, , Stable, , 5. Blood pressure, , Fluctuating, , Stable, , 6. Respiration, , Fluctuating, , Stable, , 7. Body temperature, , Fluctuating, , Stable, , 8. Neurotransmitter, , Noradrenaline, , Serotonin
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Chapter 160 t Physiology of Sleep 933, , FIGURE 160.1: Electroencephalogram during wakefulness, different stages of NREM sleep and REM sleep., NREM = Non-rapid eye movement, REM = Rapid eye movement., , Stage III: Stage of Medium Sleep, During this stage, the spindle bursts disappear. Frequency of delta waves decreases to 1 or 2 per second, and amplitude increases to about 100 µV., State IV: Stage of Deep Sleep, Delta waves become more prominent with low, , involved in the onset and maintenance of sleep., However, two centers which induce sleep are located, in brainstem:, 1. Raphe nucleus, 2. Locus ceruleus of pons., Recently, many more areas that induce sleep are, identified in the brain of animals. Inhibition of ascending reticular activating system also results in sleep., , frequency and high amplitude., 1. Role of Raphe Nucleus, , MECHANISM OF SLEEP, Sleep occurs due to the activity of some sleep-inducing, centers in brain. Stimulation of these centers induces, sleep. Damage of sleep centers results in sleeplessness, or persistent wakefulness called insomnia., , Raphe nucleus is situated in lower pons and medulla., Activation of this nucleus results in non-REM sleep. It is, due to release of serotonin by the nerve fibers arising, from this nucleus. Serotonin induces non-REM sleep., 2. Role of Locus Ceruleus of Pons, , SLEEP CENTERS, Complex pathways between the reticular formation, of brainstem, diencephalon and cerebral cortex are, , Activation of this center produces REM sleep. Noradrenaline released by the nerve fibers arising from, locus ceruleus induces REM sleep.
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934 Section 10 t Nervous System, Inhibition of Ascending Reticular, Activating System, Ascending reticular activating system (ARAS) is responsible for wakefulness because of its afferent and, efferent connections with cerebral cortex. Inhibition, of ARAS induces sleep. Lesion of ARAS leads to, permanent somnolence, i.e. coma., , APPLIED PHYSIOLOGY –, SLEEP DISORDERS, 1. INSOMNIA, Insomnia is the inability to sleep or abnormal wakefulness. It is the most common sleep disorder. It occurs, due to systemic illness or mental conditions such as, psychiatric problems, alcoholic addiction and drug, addiction., 2. HYPERSOMNIA, Hypersomnia is the excess sleep or excess need to, sleep. It occurs because of lesion in the floor of the third, ventricle, brain tumors, encephalitis, chronic bronchitis, and disease of muscles. Hypersomnia also occurs in, endocrine disorders such as myxedema and diabetes, insipidus., 3. NARCOLEPSY AND CATAPLEXY, Narcolepsy is the sudden attack of uncontrollable, sleep. Cataplexy is sudden outburst of emotion. Both, the diseases are due to hypothalamic disorders. Refer, Chapter 149 for details., 4. SLEEP APNEA SYNDROME, Sleep apnea is the temporary stoppage of breathing, repeatedly during sleep. Sleep apnea syndrome is, the disorder that involves fluctuations in the rate and, force of respiration during REM sleep with short apneic, episode. Apnea is due to decreased stimulation of, respiratory centers, arrest of diaphragmatic movements,, airway obstruction (Chapter 127) or the combination of, all these factors. When breathing stops, the resultant, hypercapnia and hypoxia stimulate respiration., Sleep apnea syndrome occurs in obesity, myxedema, enlargement of tonsil and lesion in brainstem., Common features of this syndrome are loud snoring, (Chapter 127), restless movements, nocturnal insomnia,, daytime sleepiness, morning headache and fatigue. In, severe conditions, hypertension, right heart failure and, stroke occur., , 5. NIGHTMARE, Nightmare is a condition during sleep that is, characterized by a sense of extreme uneasiness or, discomfort or by frightful dreams. Discomfort is felt, as of some heavy weight on the stomach or chest, or as uncontrolled movement of the body. After a, period of extreme anxiety, the subject wakes with a, troubled state of mind. It occurs mostly during REM, sleep. Nightmare occurs due to improper food intake,, digestive disorders or nervous disorders. It also occurs, during drug withdrawal or alcohol withdrawal., 6. NIGHT TERROR, Night terror is a disorder similar to nightmare. It is, common in children. It is also called pavor nocturnus or, sleep terror. The child awakes screaming in a state of, fright and semiconsciousness. The child cannot recollect, the attack in the morning. Nightmare occurs shortly after, falling asleep and during non-REM sleep. There is no, psychological disturbance., 7. SOMNAMBULISM, Somnambulism is getting up from bed and walking, in the state of sleep. It is also called walking during, sleep or sleep walking (somnus = sleep; ambulare = to, walk). It varies from just sitting up in the bed to walking, around with eyes open and performing some major, complex task. The episode lasts for few minutes to half, an hour. It occurs during non-REM sleep. In children,, it is associated with bedwetting or night terror without, any psychological disturbance. However, in adults it is, associated with psychoneurosis., 8. NOCTURNAL ENURESIS, Nocturnal enuresis is the involuntary voiding of urine, at bed. It is also called or bedwetting. It is common in, children. Refer Chapter 57 for details., 9. MOVEMENT DISORDERS DURING SLEEP, Movement disorders occur immediately after falling, asleep. Sleep start or hypnic jerk is the common movement disorder during sleep. It is characterized by sudden, jerks of arms or legs. Sleep start is a physiological form, of clonus., Other movement disorders are teeth grinding, (bruxism), banging the head and restless moment of, arms or legs.
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Chapter, , Epilepsy, , 161, , INTRODUCTION, TYPES OF EPILEPSY, GENERALIZED EPILEPSY, , , , , GRAND MAL, PETIT MAL, PSYCHOMOTOR EPILEPSY, , LOCALIZED EPILEPSY, , INTRODUCTION, , GENERALIZED EPILEPSY, , Epilepsy, , Generalized epilepsy is the type of epilepsy that occurs, due to excessive discharge of impulses from all parts, of the brain. It is also called general onset seizure or, general onset epilepsy., Generalized epilepsy is subdivided into three, types:, 1. Grand mal, 2. Petit mal, 3. Psychomotor epilepsy., , Epilepsy is a brain disorder characterized by convulsive, seizures or loss of consciousness or both., Convulsion and Convulsive Seizure, Convulsion refers to uncontrolled involuntary muscular, contractions. Convulsive seizure means sudden attack, of uncontrolled involuntary muscular contractions. It, occurs due to paroxysmal (sudden and usually recurring, periodically) uncontrolled discharge of impulses from, neurons of brain, particularly cerebral cortex., Epileptic, Patient affected by epilepsy is called epileptic. The, person with epilepsy remains normal in between seiz, ures. Epileptic attack develops only when excitability of, the neuron is increased, causing excessive neuronal, discharge., , GRAND MAL, Grand mal is characterized by sudden loss of conscious, ness, followed by convulsion. Just before the onset of, convulsions, the person feels the warning sensation in, the form of some hallucination. It is called epileptic, aura., , Convulsions occur in two stages:, a. Tonic stage, b. Clonic stage., , TYPES OF EPILEPSY, , Tonic Stage, , Epilepsy is divided into two categories:, 1. Generalized epilepsy, 2. Localized epilepsy., , Initially, seizure is characterized by tonic contractions of, muscle leading to spasm. Spasm causes twisting facial, features, flexion of arm and extension of lower limbs.
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936 Section 10 t Nervous System, Clonic Stage, Clonic convulsions develop after the tonic stage. This, , stage is characterized by violent jerky movements of, limbs and face due to alternate severe contraction and, relaxation of muscles., At the end of attack, alternative tonic and clonic, convulsions are seen. During the entire period of, seizure, tongue may be bitten., Electroencephalogram (EEG) shows fast waves with, a frequency of 15 to 30 per second during tonic stage., Slow and large waves appear during clonic phase. After, the attack, slow waves are recorded for some time. In, between seizures, EEG shows delta waves in all types, of epileptics., Causes of Grand Mal, Cause of grand mal epilepsy is the excess neural, activity in all parts of brain. Cause for stoppage of, attack is neuronal fatigue. Factors which accelerate, the neural activity resulting in grand mal epilepsy are:, i. Strong emotional stimuli, ii. Hyperventilation and alkalosis, iii. Effects of some drugs, iv. Uncontrolled high fever, v. Loud noises or bright light, vi. Traumatic lesions in any part of brain., PETIT MAL, In this type of epilepsy, the person becomes unconscious suddenly without any warning. The unconscious, ness lasts for a very short period of 3 to 30 seconds., Convulsions do not occur. However, the muscles of, face show twitchlike contractions and there is blinking, of eyes. Afterwards, the person recovers automatically, and becomes normal. Frequency of attack may be, once in many months or many attacks may appear in, rapid series. It usually occurs in late childhood and dis, appears completely at the age of 30 or above., EEG recording shows slow and large waves during, the attack. Each wave is followed by a sharp spike. This, , type of waves appear from recording over any part of, the cerebral cortex indicating the involvement of whole, brain. Delta waves appear in between the seizures., Causes of Petit Mal, Cause of petit mal is not known. It occurs in conditions, like head injury, stroke, brain tumor and brain infection., PSYCHOMOTOR EPILEPSY, Psychomotor epilepsy is characterized by emotional, outbursts such as abnormal rage, sudden anxiety, fear, or discomfort. There is amnesia or a confused mental, state for some period. Some persons have the tendency, to attack others bodily or rub their own face vigorously. In, most cases, the persons are not aware of their activities., Some persons are very well aware of the actions, but, still the abnormal actions cannot be controlled., EEG recordings show low frequency rectangular, waves, ranging between 2 and 4 per second., Causes of Psychomotor Epilepsy, Causes of psychomotor epilepsy are the abnormalities, in temporal lobe and tumor in hypothalamus and, other regions of limbic system like amygdala and, hippocampus., , LOCALIZED EPILEPSY, Epilepsy that occurs because of excessive discharge, of impulses from one part of brain is called localized, epilepsy. It is otherwise known as local or focal epilepsy, or local seizure. It involves only a localized area of, cerebral cortex or the deeper parts of cerebellum, which, are affected by tumor, abscess or vascular defects., The abnormality starts from a particular area and, spreads to adjacent areas, developing slowspreading, muscular contractions. Contractions usually start in the, mouth region and spread down towards the legs. This, type of seizure is also known as jacksonian epilepsy., Causes of Localized Epilepsy, Localized epilepsy is caused by brain tumor.
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Higher Intellectual, Functions, , Chapter, , 162, , HIGHER INTELLECTUAL FUNCTIONS, LEARNING, , , , DEFINITION, CLASSIFICATION, , MEMORY, , , , , , , , , , DEFINITION, ANATOMICAL BASIS, PHYSIOLOGICAL BASIS, CHEMICAL OR MOLECULAR BASIS, CONSOLIDATION, CLASSIFICATION, DRUGS FACILITATING MEMORY, APPLIED PHYSIOLOGY, , CONDITIONED REFLEXES, , , , , , , , , , DEFINITION, CLASSIFICATION, CLASSICAL CONDITIONED REFLEXES, TYPES AND PROPERTIES OF CLASSICAL CONDITIONED REFLEXES, POSITIVE CONDITIONED REFLEXES, NEGATIVE CONDITIONED REFLEXES, INSTRUMENTAL OR OPERANT CONDITIONED REFLEXES, PHYSIOLOGICAL BASIS OF CONDITIONED REFLEXES, , SPEECH, , , , , , , , , , , DEFINITION, MECHANISM, DEVELOPMENT, NERVOUS CONTROL, APPLIED PHYSIOLOGY, APHASIA, DYSARTHRIA OR ANARTHRIA, DYSPHONIA, STAMMERING, , HIGHER INTELLECTUAL FUNCTIONS, Higher intellectual functions are very essential to make, up the human mind. These functions are also called, higher brain functions or higher cortical functions. The, , extensive outer layer of gray matter in cerebral cortex is, responsible for higher intellectual functions., Conditioned reflex forms the basis of all higher, intellectual functions.
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938 Section 10 t Nervous System, , LEARNING, , MEMORY, , DEFINITION, , DEFINITION, , Learning is defined as the process by which new, information is acquired. It alters the behavior of a person, on the basis of past experience., , Memory is defined as the ability to recall past experience, or information. It is also defined as retention of learned, materials. There are various degrees of memory. Some, memories remain only for few seconds, while others, last for hours, days, months or even years together., , CLASSIFICATION OF LEARNING, Learning is classified into two types:, 1. Non-associative learning, 2. Associative learning., 1. Non-associative Learning, Non-associative learning involves response of a person, to only one type of stimulus. It is based on two factors:, i. Habituation, ii. Sensitization., i. Habituation, Habituation means getting used to something, to, which a person is constantly exposed. When a person, is exposed to a stimulus repeatedly, he starts ignoring, the stimulus slowly. During first experience, the event, (stimulus) is novel and evokes a response. However,, it evokes less response when it is repeated. Finally,, the person is habituated to the event (stimulus) and, ignores it., ii. Sensitization, Sensitization is a process by which the body is made, to become more sensitive to a stimulus. It is called, amplification of response. When a stimulus is applied, repeatedly, habituation occurs. But, if the same, stimulus is combined with another type of stimulus,, which may be pleasant or unpleasant, the person, becomes more sensitive to original stimulus., For example, a woman is sensitized to crying sound, of her baby. She gets habituated to different sounds, around her and sleep is not disturbed by these sounds., However, she suddenly wakes up when her baby cries, because of sensitization to crying sound of the baby., Thus, sensitization increases the response to an, innocuous stimulus when that stimulus is applied after, another type of stimulus., , ANATOMICAL BASIS OF MEMORY, Anatomical basis of memory is the synapse in brain., Synapse for memory coding is slightly different from, other synapses. Two separate presynaptic terminals are, present here. One of the terminals is primary presynaptic, terminal, which ends on postsynaptic neuron as in, conventional synapse. This terminal is called sensory, terminal, because sensations are transmitted to the, postsynaptic neuron through this terminal (Fig. 162.1)., Other presynaptic terminal ends on the sensory, terminal itself. This terminal is called facilitator terminal., When, sensory terminal is stimulated alone without facilitator terminal, the firing from sensory terminal, leads to habituation, i.e. the firing decreases slowly., On the other hand, if both the terminals are stimulated,, facilitation occurs and the signals remain strong for, long period, i.e. for few months to few years., PHYSIOLOGICAL BASIS OF MEMORY, Memory is stored in brain by the alteration of synaptic, transmission between the neurons involved in memory., , 2. Associative Learning, Associative learning is a complex process. It involves, learning about relations between two or more stimuli, at a time. Classic example of associative learning is, the conditioned reflex, which is described later in this, chapter., , FIGURE 162.1: Synaptic terminal for memory encoding
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Chapter 162 t Higher Intellectual Functions 939, Storage of memory may be facilitated or habituated, depending upon many factors, such as neurotransmitter,, synaptic transmission, functional status of brain, etc., , CHEMICAL OR MOLECULAR, BASIS OF MEMORY, , Facilitation, , Molecular basis of memory can be explained by, memory engram. Memory engram is a process by which, memory is facilitated and stored in the brain by means, of structural and biochemical changes. Often, it is also, called memory trace., , Facilitation is the process by which memory storage is, enhanced. It involves increase in synaptic transmission, and increased postsynaptic activity. Often, facilitation, is referred as positive memory., The process involved in facilitation of memory is, called memory sensitization., Habituation, Habituation is the process by which memory storage is, attenuated (attenuation = decrease in strength, effect, , or value). It involves reduction in synaptic transmission, and slow stoppage of postsynaptic activity. Sometimes,, habituation is referred as negative memory., Basis for Short-term Memory, Basic mechanism of memory is the development of, new neuronal circuits by the formation of new synapses, and facilitation of synaptic transmission. Number of, presynaptic terminals and size of the terminals are also, increased. This forms the basis of short-term memory., Basis for Long-term Memory, When neuronal circuit is reinforced by constant activity,, memory is consolidated and encoded into different, areas of the brain. This encoding makes memory a, permanent or a long-term memory., Sites of Encoding, Hippocampus and Papez circuit (closed circuit, between hippocampus, thalamus, hypothalamus and, corpus striatum) are the main sites of memory encoding (Chapter 153). Frontal and parietal areas are also, involved in memory storage., , Memory Engram, , Molecular Basis of Facilitation, Molecular mechanism of facilitation is given in Figure, 162.2. In this process, the neurotransmitter serotonin, plays major role. Calcium ions increase the release of, serotonin, which facilitates the synaptic transmission to, a great extent, leading to memory storage., Molecular Basis of Habituation, Habituation is due to passive closure of calcium, channels of terminal membrane. Hence, the release of, transmitter decreases, resulting in decrease in number, of action potential in the postsynaptic neuron. So, the, signals become weak and weakening of signals leads, to habituation., CONSOLIDATION OF MEMORY, The process by which a short-term memory is, crystallized into a long-term memory is called memory, consolidation. Consolidation causes permanent facilitation of synapses. It is possible by rehearsal mechanism,, i.e. rehearsal of same information again and again, accelerates and potentiates the degree of transfer of, short-term memory into long-term memory. This is what, happens in memorizing a poem or a phrase., CLASSIFICATION OF MEMORY, Memory is classified by different methods, on the basis, of various factors., , Experimental Studies of Memory – Aplysia, , Short-term Memories and Long-term Memories, , Most of the experimental studies of memory and, learning are based on the research carried out in the sea, hare (sea snail) called Aplysia. This animal is useful in, brain research because it has a simple uncomplicated, nervous system that can be easily approached in living, animal with simple dissection. Another advantage of, this snail is that the individual nerve cells are large and, brightly colored., Nobel laureate, Eric Kandel was the pioneer to, use Aplysia for the studies of memory and learning., , Generally, memory is classified as short-term memory, and long-term memory., 1. Short-term memory, Short-term memory is the recalling events that, happened very recently, i.e. within hours or days. It is, also known as recent memory. For example, telephone, number that is known today may be remembered till, tomorrow. But if it is not recalled repeatedly, it may be, forgotten on the third day.
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940 Section 10 t Nervous System, day of schooling, birthday celebration of previous year,, picnic enjoyed last week, etc. Long-term memory is, more resistant and is not disrupted easily., Explicit and Implicit Memories, Physiologically, memory is classified into two types,, namely explicit memory and implicit memory., 1. Explicit memory, Explicit memory is defined as the memory that involves, conscious recollection of past experience. It consists, of memories regarding events, which occurred in the, external world around us. The information stored may, be about a particular event that happened at a particular, time and place. Explicit memory is otherwise known, as declarative memory or recognition memory., Examples of explicit memory are recollection of, a birthday party celebrated three days ago, events, taken place while taking breakfast, etc., Explicit memory involves hippocampus and medial, part of temporal lobe., 2. Implicit memory, Implicit memory is defined as the memory in which past, experience is utilized without conscious awareness., It helps to perform various skilled activities properly., Implicit memory is otherwise known as non-declarative, memory or skilled memory., Examples of implicit memory are cycling, driving,, playing tennis, dancing, typing, etc., Implicit memory involves the sensory and motor, pathways., Memories Depending upon Duration, , FIGURE 162.2: Memory engram, , Depending upon duration, memory is classified into, three types:, 1. Sensory memory, 2. Primary memory, 3. Secondary memory., 1. Sensory memory, , Short-term memory may be interrupted by many, factors such as stress, trauma, drug abuse, etc., There is another form of short-term memory called, working memory. It is concerned with recollection of, past experience for a very short period, on the basis of, which an action is executed., , Sensory memory is the ability to retain sensory signals, in sensory areas of brain, for a very short period of few, seconds after the actual sensory experience, i.e. few, hundred milliseconds. But, the signals are replaced by, new sensory signals in less than 1 second. It is the, initial stage of memory. It resembles working memory., , 2. Long-term memory, , 2. Primary memory, , Long-term memory is the recalling of events of weeks,, months, years or sometimes lifetime. It is otherwise, called the remote memory. Examples are, recalling first, , Primary memory is the memory of facts, words, numbers,, letters or other information retained for few minutes, at a time. For example, after searching and finding a
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Chapter 162 t Higher Intellectual Functions 941, telephone number in the directory, we remember the, number for a short while. After appreciating beautiful, scenery, the details of it could be recalled for some, time. Afterwards, it disappears from the memory., Characteristic feature of this type of memory is, that the information is available for recall easily from, memory store itself. One need not search or squeeze, through the mind, but this memory is easily replaced, by new bits of memory, i.e. by looking into another, telephone number, the first one may disappear., 3. Secondary memory, Secondary memory is the storage of information, in brain for a longer period. The information could, be recalled after hours, days, months or years. It is, also called fixed memory or permanent memory. It, resembles long-term memory., DRUGS FACILITATING MEMORY, Several stimulants for central nervous system are, shown to improve learning and memory in animals., Common stimulants are caffeine, physostigmine,, amphetamine, nicotine, strychnine and metrazol., All these substances mentioned above facilitate the, consolidation of memory., APPLIED PHYSIOLOGY – ABNORMALITIES, OF MEMORY, 1. Amnesia, Loss of memory is known as amnesia. Amnesia is, classified into two types:, i. Anterograde amnesia: Failure to establish new, long-term memories. It occurs because of lesion, in hippocampus., ii. Retrograde amnesia: Failure to recall past, remote long-term memory. It occurs in temporal, lobe syndrome., 2. Dementia, Dementia is the progressive deterioration of intellect,, emotional control, social behavior and motivation, associated with loss of memory. It is an age-related, disorder. Usually, it occurs above the age of 65 years., When it occurs under the age of 65, it is called presenile, , below). Other common causes of dementia are hydrocephalus, Huntington chorea, Parkinson disease, viral, encephalitis, HIV infection, hypothyroidism, hypoparathyroidism, Cushing syndrome, alcoholic intoxication,, poisoning by high dose of barbiturate, carbon monoxide,, heavy metals, etc., Clinical features, Common features are loss of recent memory, lack of, thinking and judgment and personality changes. As, the disease progresses, psychiatric features begin to, appear. Motor functions are also affected. Finally, the, patient has to lead a vegetative life without any thinking, power. The person is speechless and is unable to, understand anything., There is no effective treatment for this disorder., Physostigmine, which inhibits cholinesterase causes, moderate improvement., 3. Alzheimer Disease, Alzheimer disease is a progressive neurodegenerative, disease. It is due to degeneration, loss of function and, death of neurons in many parts of brain, particularly, cerebral hemispheres, hippocampus and pons., There is reduction in the synthesis of most of the, neurotransmitters, especially acetylcholine. Synthesis, of acetylcholine decreases due to lack of enzyme, choline acetyltransferase. Norepinephrine synthesis, decreases because of degeneration of locus ceruleus., Dementia is the common feature of this disease., , CONDITIONED REFLEXES, DEFINITION, Conditioned reflex is the acquired reflex that requires, learning, memory and recall of previous experience. It is, acquired after birth and it forms the basis of learning., Conditioned reflex is different from unconditioned, reflex (Table 162.1). Unconditioned reflex is the inborn, reflex, which does not need previous experience., TABLE 162.1: Conditioned reflex Vs unconditioned reflex, Conditioned reflex, , Unconditioned reflex, , Acquired after birth, , Inborn reflex, , dementia., , Needs previous experience, , Does not need previous, experience, , Causes, , Involves learning and, memory, , Does not involve learning, and memory, , Elicited by conditioned, stimulus, , Elicited by unconditioned, stimulus, , Dementia occurs due to many reasons. Most common, cause of dementia is Alzheimer disease. In about, 75% of cases, dementia is due to this disease (given
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942 Section 10 t Nervous System, CLASSIFICATION OF, CONDITIONED REFLEXES, Conditioned reflexes are classified into two types:, A. Classical conditioned reflexes, B. Instrumental conditioned reflexes., CLASSICAL CONDITIONED REFLEXES, Classical conditioned reflexes are those reflexes,, which are established by a conditioned stimulus,, followed by an unconditioned stimulus., Method of Study – Pavlov’s Bell-Dog Experiments, Various types of classical conditioned reflexes and, their properties are demonstrated by the classical belldog experiments (salivary secretion experiments),, done by Ivan Pavlov and his associates., In dogs, the duct of parotid gland or submandibular, gland was taken outside through cheek or chin, respectively and the saliva was collected by some, special apparatus. Apparatus consisted of a funnel,, which is sealed over the opening of the duct. Salivary, secretion was measured in drops by means of an, electrical recorder., TYPES AND PROPERTIES OF, CLASSICAL CONDITIONED REFLEXES, Classical conditioned reflexes are classified into two, groups according to the properties of reflexes, namely, excitation or inhibition:, I. Positive or excitatory conditioned reflexes, II. Negative conditioned reflexes., POSITIVE CONDITIONED REFLEXES, (EXCITATION OF CONDITIONED REFLEXES), Types of positive conditioned reflexes:, 1. Primary conditioned reflex, 2. Secondary conditioned reflex, 3. Tertiary conditioned reflex., 1. Primary Conditioned Reflex, Primary conditioned reflex is the reflex developed, with one unconditioned stimulus and one conditioned, stimulus. This reflex is established in the following way., The animal is fed with food (unconditioned stimulus)., Simultaneously a flash of light (conditioned stimulus), is also shown. Both the stimuli are repeated for some, days. After the development of reflex, the flash of light, (conditioned stimulus) alone causes salivary secretion, without food (unconditioned stimulus)., , 2. Secondary Conditioned Reflex, Secondary conditioned reflex is the reflex developed, with one unconditioned stimulus and two conditioned, stimuli. After establishment of a conditioned reflex with, one conditioned stimulus, another conditioned stimulus, is applied along with the first one. For example, the, animal is fed with food (unconditioned reflex) and, simultaneously a flash of light (first conditioned, stimulus) and a bell sound (second conditioned, stimulus) are applied. After development of the reflex,, bell sound (second conditioned stimulus) alone can, cause salivary secretion (Fig. 162.3)., 3. Tertiary Conditioned Reflex, In this reflex, a third conditioned stimulus is added, and the reflex is established. But, the reflex with more, than three conditioned stimuli is not possible. Many, types of conditioned stimuli associated with sight and, hearing were employed by Pavlov., NEGATIVE CONDITIONED REFLEXES, (INHIBITION OF CONDITIONED REFLEXES), The established conditioned reflexes can be inhibited, by some factors. The inhibition is of two types:, 1. External or indirect inhibition, 2. Internal or direct inhibition., 1. External or Indirect Inhibition, Established conditioned reflex is inhibited by some form, of stimulus, which is quite different from the conditioned, stimulus. It is not related to conditioned stimulus., For example, some disturbing factors like sudden, entrance of a stranger, sudden noise or a strong smell, can abolish the conditioned reflex and inhibit salivary, secretion. This extra stimulus evokes the animal’s, curiosity and distracts the attention. According to, Pavlov, it evokes an investigatory reflex. If the extra, (inhibitory) stimulus is repeated for some time, its, inhibitory effect gets weakened or abolished., 2. Internal or Direct Inhibition, There are four ways in which the established, conditioned reflex is abolished by direct or internal, factors, which are related to the conditioned stimulus., i. Extinction of conditioned reflex, ii. Conditioned inhibition, iii. Inhibition by delay or delayed conditioned reflex, iv. Differential inhibition.
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Chapter 162 t Higher Intellectual Functions 943, , FIGURE 162.3: Conditioned reflexes, , i. Extinction of conditioned reflex, , iv. Differential inhibition, , Extinction is the failure of conditioned reflex. It occurs, if an established conditioned reflex is not reinforced, by unconditioned stimulus. After establishing a, conditioned reflex, the conditioned stimulus must be, coupled with unconditioned stimulus now and then,, i.e. the conditioned stimulus must be reinforced by, unconditioned stimulus. If a conditioned stimulus is, given repeatedly several times, without reinforcing it by, unconditioned stimulus, there is failure of conditioned, reflex. However, the reflex is not abolished if the, unconditioned reflex is also used in between., , Differential inhibition is the failure of conditioned reflex, that occurs when the conditioned stimulus is altered., When an animal is trained or conditioned for a particular, type of conditioned stimulus and if this stimulus is altered, even slightly, the response does not occur. The animal, is able to discriminate the difference. For example, the, alteration in frequency of sound or intensity of light, abolishes the conditioned reflex (Table 162.2)., , ii. Conditioned inhibition, , Instrumental conditioned reflexes are those reflexes, in which the behavior of the person is instrumental., This type of reflexes is developed by the conditioned, stimulus, followed by a reward or a punishment. The, instrumental conditioned reflexes are also called, operant conditioned reflexes or Skinner conditioning., During the development of this type of reflexes,, the animal is taught to perform some task, in order to, obtain a reward or to avoid a punishment. Accordingly,, the instrumental conditioned reflexes are of several, types, such as:, 1. Conditioned avoidance reflex, 2. Food avoidance reflex, 3. Conditioned reward reflex., , Conditioned inhibition is the failure of conditioned reflex, due to introduction of an unknown (new) conditioned, stimulus. When a conditioned stimulus like flash of, light is effective, if another conditioned stimulus like a, bell sound is applied along with this stimulus suddenly,, the response does not occur. Of course, if these two, conditioned stimuli are given with unconditioned, stimulus (food) repeatedly, the secondary conditioned, reflex is developed., iii. Inhibition by delay or delayed conditioned reflex, Inhibition by delay is the absence of response or delayed, response that occurs while eliciting a conditioned reflex by, delaying the unconditioned stimulus. While establishing, a conditioned reflex, the conditioned stimulus (light or, sound) must be followed by unconditioned stimulus, (food) immediately. If the unconditioned stimulus is, applied after a long period, response may be absent or, delayed. The reflex is called delayed conditioned reflex., , INSTRUMENTAL OR OPERANT, CONDITIONED REFLEXES, , Conditioned Avoidance Reflex, Conditioned avoidance reflex is the reflex by which, the animal is trained to avoid an electric shock, by, pressing a bar.
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944 Section 10 t Nervous System, TABLE 162.2: Causes for inhibition of conditioned reflex, Type of inhibition, External inhibition, , Internal inhibition, , Cause, Disturbing factors like a stranger, noise or strong smell, , Extinction of conditioned reflex, , Failure to reinforce the conditioned reflex by unconditioned stimulus, , Conditioned inhibition, , Introduction of unknown (new) conditioned stimulus, , Inhibition by delay, , Delay in applying unconditioned stimulus, , Differential inhibition, , Alteration of conditioned stimulus, , Food Avoidance Conditioning, If an animal is given a tasty food along with injection, of a drug, which produces nausea or sickness, the, animal starts avoiding or hating that food. It is called, , influences of motor impulses from respective motor, areas of the cerebral cortex., DEVELOPMENT OF SPEECH, , food aversion conditioning., , First Stage, , Conditioned Reward Reflex, , First stage in the development of speech is the, association of certain words with visual, tactile,, auditory and other sensations, aroused by objects, in the external world. Association of words with other, sensations is stored as memory., , If the animal is rewarded by a banana by pressing a, bar, the animal repeatedly presses the bar. It is the, conditioned reward reflex., Instrumental conditioned reflexes play an important, role during the learning processes of a child. These, conditioned reflexes are also responsible for the, behavior pattern of an individual., PHYSIOLOGICAL BASIS, OF CONDITIONED REFLEXES, Learning and memory form the physiological basis of, conditioned reflexes., , SPEECH, DEFINITION, Speech is defined as the expression of thoughts by, production of articulate sound, bearing a definite, meaning. It is one of the highest functions of brain., When a sound is produced verbally, it is called, the speech. If it is expressed by visual symbols, it is, known as writing. If visual symbols or written words are, expressed verbally, that becomes reading., MECHANISM OF SPEECH, Speech depends upon coordinated activities of central, speech apparatus and peripheral speech apparatus., Central speech apparatus consists of higher centers,, i.e. the cortical and subcortical centers. Peripheral, speech apparatus includes larynx or sound box,, pharynx, mouth, nasal cavities, tongue and lips. All, the structures of peripheral speech apparatus function, in coordination with respiratory system, with the, , Second Stage, New neuronal circuits are established during the, development of speech. When a definite meaning has, been attached to certain words, pathway between the, auditory area (Heschl area; area 41) and motor area, for the muscles of articulation, which helps in speech, (Broca area 44) is established. The child attempts to, formulate and pronounce the learnt words., Role of Cortical Areas in the, Development of Speech, Development of speech involves integration of three, important areas of cerebral cortex:, 1. Wernicke area, 2. Broca area, 3. Motor area., Role of Wernicke area – Speech understanding, Understanding of speech begins in Wernicke area that, is situated in upper part of temporal lobe. It sends fibers, to Broca area through a tract called arcuate fasciculus., Wernicke area is responsible for understanding the, visual and auditory information required for the production of words. After understanding the words, it, sends the information to Broca area., Role of Broca area – Speech synthesis, Speech is synthesized in the Broca area. It is situated, adjacent to the motor area, responsible for the movements of tongue, lips and larynx, which are necessary
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Chapter 162 t Higher Intellectual Functions 945, for speech. By receiving information required for, production of words from Wernicke area, the Broca, area develops the pattern of motor activities required, to verbalize the words. The pattern of motor activities, is sent to motor area., Role of motor area – Activation of peripheral, speech apparatus, By receiving the pattern of activities from Broca area,, motor area activates the peripheral speech apparatus., It results in initiation of movements of tongue, lips and, larynx required for speech., Later, when the child is taught to read, auditory, speech is associated with visual symbols (area 18)., Then, there is an association of the auditory and visual, areas with the motor area for the muscles of hand., Now, the child is able to express auditory and visual, impressions in the form of written words., NERVOUS CONTROL OF SPEECH, Speech is an integrated and a well-coordinated motor, phenomenon. So, many parts of cortical and subcortical, areas are involved in the mechanism of speech., Subcortical areas concerned with speech are, controlled by cortical areas of dominant hemisphere., In about 95% of human beings, the left cerebral hemisphere is functionally dominant and those persons are, right handed. Following are the motor and sensory, cortical areas concerned with speech., A. Motor Areas, 1. Broca area, Broca area is also called speech center, motor speech, area or lower frontal area. It includes areas 44 and 45., These areas are situated in lower part of lateral surface, of prefrontal cortex., Broca area controls the movements of structures, (tongue, lips and larynx) involved in vocalization., 2. Upper frontal motor area, Upper frontal motor area is situated in paracentral gyrus, over the medial surface of cerebral hemisphere. It, controls the coordinated movements involved in writing., B. Sensory Areas, 1. Secondary auditory area, Secondary auditory area or auditopsychic area includes, area 22. It is situated in the superior temporal gyrus. It is, concerned with the interpretation of auditory sensation, and storage of memories of spoken words., , 2. Secondary visual area, Secondary visual area or visuopsychic area includes, area 18. It is present in angular gyrus of the parietal, cortex. This area is concerned with the interpretation of, visual sensation and storage of memories of the visual, symbols., C. Wernicke Area, Wernicke area is situated in the upper part of temporal, lobe. This area is responsible for the interpretation, of auditory sensation. It also plays an important role, in speech. It is responsible for understanding the, auditory information about any word and sending the, information to Broca area (Table 162.3)., APPLIED PHYSIOLOGY – DISORDERS OF, SPEECH, Speech disorder is a communication disorder, characterized by disrupted speech. It is of four types:, I. Aphasia, II. Anarthria or dysarthria, III. Dysphonia, IV. Stammering., APHASIA, Aphasia is defined as the loss or impairment of speech, due to brain damage (in Greek, aphasia = without, speech). It is an acquired disorder and it is distinct from, developmental disorders of speech or other speech, disorders like dysarthria. Aphasia is not due to paralysis, of muscles of articulation. It is due to damage of speech, centers., Damage of speech centers impairs the expression, and understanding of spoken words. It also affects, reading and writing. Speech function is localized to left, hemisphere in most of the people., Aphasia may be associated with other speech, disorders, which also occur due to brain damage., Causes for Aphasia, Usually aphasia occurs due to damage of one or, more speech centers, which are situated in cerebral, cortex (Table 162.4). Damage of speech centers, occurs due to:, 1. Stroke, 2. Head injury, 3. Severe blow to head, 4. Cerebral tumors, 5. Brain infections, 6. Degenerative diseases.
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946 Section 10 t Nervous System, TABLE 162.3: Role of cortical areas in control of speech, Cortical areas, Motor areas, , Function, , Broca area: Areas 44 and 45, , Controls movement of structures involved in speech, , Upper frontal motor area, , Controls movements involved in writing, , Secondary auditory area: Area 22, , Concerned with interpretation of auditory sensation, Concerned with storage of memories of spoken words, , Secondary visual area: Area 18, , Concerned with interpretation of visual sensation, Concerned with storage of memories of visual symbols, , Sensory areas, , Concerned with interpretation of auditory sensation, Concerned with understanding auditory information and sending it, to Broca area, , Wernicke area, , TABLE 162.4: Features and causes of different types of aphasia, Type of aphasia, , Features, , Cause, , Broca aphasia, , Non-fluent speech problem, , Lesion in left frontal lobe, , Wernicke aphasia, , Speech without any meaning, , Lesion in left temporal lobe, , Global aphasia, , Combined features of Broca aphasia, and Wernicke aphasia, , Widespread lesion in speech areas of left cerebral, hemisphere, , Nominal aphasia, , Inability to name the familiar objects, , Lesion in posterior temporal and inferior parietal gyri, , Motor aphasia, , Difficulty in uttering individual words, , Defect in pathway between left speech center and, precentral cortex, , Auditory aphasia, , Inability to understand spoken words, , Lesion in secondary auditory area, , Visual aphasia, , Inability to understand written symbols, , Lesion in secondary visual area, , Agraphia, , Inability to write, , Defect in pathway between cortical areas concerned, with writing, , Usually, in conditions like head injury, aphasia, occurs suddenly and in conditions like infections, or cerebral tumors, it develops slowly. In children,, traumatic aphasia can develop by exposure to a, horrifying event, without any brain damage. It may be, cured with psychological treatment., Types of Aphasia, Aphasia is classified by different methods. The simple, and convenient clinical classification divides aphasia, into five types:, 1. Broca aphasia, 2. Wernicke aphasia, 3. Global aphasia, 4. Nominal aphasia, 5. Other types of aphasia., 1. Broca aphasia, Broca aphasia is the non-fluent speech problem. It, occurs due to lesion in left frontal lobe of cerebral, cortex. It is also known as expressive aphasia or anter-, , ior aphasia. The affected persons do not complete the, sentences because of their inability to construct the, sentences. They often talk in short phrases by omitting, small words such as ‘and’, ‘is’, ‘for’, etc. They make, great efforts even to initiate speech., Persons with Broca aphasia are able to understand, spoken or written words. Often, they are affected by, weakness or paralysis of right arm or leg. It is due to, damage of frontal lobe, which is also responsible for, motor activities., 2. Wernicke aphasia, Wernicke aphasia is the speech without any meaning., It is also called receptive aphasia or posterior aphasia., Wernicke aphasia occurs due lesion in left temporal, lobe. It is characterized by fluent speech. The affected, persons speak long sentences but without any, meaning. They use incorrect or non-existent words, and cannot speak sensibly. This type of speech is, known as jargon speech., These individuals are unable to understand others’, speech. Because of this weakness, they are unaware
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Chapter 162 t Higher Intellectual Functions 947, of their own mistakes while speaking. Often, they are, mistaken as psychiatric patients., Wernicke aphasia is not associated with paralysis, or weakness of muscles because, the injury does not, involve the centers concerned with movements., , Head’s Classification of Aphasia, , 3. Global aphasia, , Henry Head was the pioneer scientist in the field of, , Global aphasia is the type of aphasia characterized, by combined features of Broca aphasia and Wernicke, aphasia. It is due to widespread lesion in speech, areas caused by infarction of left cerebral hemisphere., It is the most common type of aphasia. The affected, persons can neither speak nor understand the spoken, words. They cannot read and write also. So they have, severe communication problems., 4. Nominal aphasia, Nominal aphasia is the speech disorder characterized, by inability in naming the familiar objects. It is also called, anomic aphasia or amnesic aphasia. It is due to lesion, in posterior temporal and inferior parietal gyri., 5. Other types of aphasia, i. Motor aphasia: It is the speech disorder caused, by the defect in the pathway between left, speech areas and excitomotor or precentral, cortex (Chapter 152). It is also known as verbal, aphasia or dyspraxia or apraxia of speech. It is, characterized by difficulty in uttering individual, words due to lack of coordination between, central speech apparatus (higher cortical, centers) and peripheral speech apparatus. The, affected persons are able to decide what to talk., But they cannot pronounce all the words. They, are able to pronounce only few monosyllables, such as ‘yes’ or ‘no’., ii. Sensory aphasia: It is the inability to understand, words or symbols. It is of two types:, a. Auditory aphasia: Inability to understand, the spoken words. It is also called word, deafness. It is due to the lesion in secondary, auditory area., b. Visual aphasia: Inability to understand written, symbols (difficulty in reading). It is also called, word blindness or dyslexia and it occurs due, to the lesion in secondary visual area., iii. Agraphia: Agraphia means inability to write., There is no defect in the muscles of the hand, concerned with writing. The subject can read, and speak. Agraphia is due to the defect in, the connection between the cortical areas, , concerned with writing. Agraphia differs from, dysgraphia, which is characterized by distorted, writing or writing incorrect letters., , speech disorders and he was the first one to classify, aphasia. In 1926, he classified aphasia into four types., Head’s classification of aphasia is given in Table 162.5., DYSARTHRIA OR ANARTHRIA, , The term dysarthria refers to disturbed articulation., Anarthria means inability to speak. Dysarthria or, anarthria is defined as the difficulty or inability to speak, because of paralysis or ataxia of muscles involved in, articulation. Psychic aspect of speech is not affected., The spoken and written words are understood., Causes of Dysarthria, Dysarthria is caused by damage of brain or the nerves, that control the muscles involved in speech. It occurs in, conditions like stroke, brain injury, degenerative disease, like Parkinson disease and Huntington disease., DYSPHONIA, Dysphonia is a voice disorder. Often, it is characterized, by hoarseness and a sore or a dry throat. Hoarseness, means the difficulty in producing sound while trying to, speak or a change in the pitch or loudness of voice. The, voice may be weak, breathy, scratchy or husky., Causes of Dysphonia, 1., 2., 3., 4., 5., 6., , Trauma of vocal cords, Paralysis of vocal cords, Lumps (nodules) on vocal cords, Inflammation of larynx, Hypothyroidism, Stress (psychological dysphonia)., TABLE 162.5: Head’s classification of aphasia, Type of aphasia, , Features, , Verbal aphasia, , Inability in formation of words, , Syntactical aphasia, , Inability to arrange words in proper, sequence, , Semantic aphasia, , Inability to recognize the, significance of words, , Nominal aphasia, , Inability to name the familiar objects
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948 Section 10 t Nervous System, STAMMERING, Stammering or shuttering is a speech disorder characterized by hesitations and involuntary repetitions of, certain syllables or words. It is also described as a, speech disorder in which normal flow of speech is, disturbed by repetitions, prolongations or abnormal, block or stoppage of sound and syllables. It is due to the, , neurological incoordination of speech and it is common, in children., Stammering is associated with some unusual facial, and body movements. Exact cause for stammering is, not known. It is thought that stammering may be due to, genetic factors, brain damage, neurological disorders or, anxiety.
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Cerebrospinal Fluid (CSF), , Chapter, , 163, , INTRODUCTION, PROPERTIES AND COMPOSITION, FORMATION, , , , , , , , , , , SITE OF FORMATION, MECHANISM OF FORMATION, SUBSTANCES AFFECTING THE FORMATION, , CIRCULATION, ABSORPTION, PRESSURE EXERTED, FUNCTIONS, COLLECTION, , , LUMBAR PUNCTURE, , BLOOD-BRAIN BARRIER, , , , STRUCTURE, FUNCTIONS, , BLOOD-CEREBROSPINAL FLUID BARRIER, APPLIED PHYSIOLOGY – HYDROCEPHALUS, , INTRODUCTION, Cerebrospinal fluid (CSF) is the clear, colorless and, transparent fluid that circulates through ventricles of, brain, subarachnoid space and central canal of spinal, cord. It is a part of extracellular fluid (ECF)., , PROPERTIES AND COMPOSITION, OF CEREBROSPINAL FLUID, Properties, Volume, Rate of formation, Specific gravity, Reaction, , :, :, :, :, , 150 mL (100 mL to 200 mL), 0.3 mL per minute, 1.005, Alkaline., , Composition, Composition of CSF is given in Figure 163.1. Since CSF, is a part of ECF, it contains more amount of sodium, , than potassium. CSF also contains some lymphocytes., CSF secreted by ventricle does not contain any cell., Lymphocytes are added when CSF flows in the spinal, cord., , FORMATION OF CEREBROSPINAL FLUID, SITE OF FORMATION, CSF is formed by choroid plexuses, situated within, the ventricles. Choroid plexuses are tuft of capillary, projections present inside the ventricles and are, covered by pia mater and ependymal covering. A large, amount of CSF is formed in the lateral ventricles., MECHANISM OF FORMATION, CSF is formed by the process of secretion that, involves active transport mechanism. Formation of, CSF does not involve ultrafiltration or dialysis.
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950 Section 10 t Nervous System, , ABSORPTION OF CEREBROSPINAL FLUID, CSF is mostly absorbed by the arachnoid villi into dural, sinuses and spinal veins. Small amount is absorbed, along the perineural spaces into cervical lymphatics, and into the perivascular spaces., The mechanism of absorption is by filtration due to, pressure gradient between hydrostatic pressure in the, subarachnoid space fluid and the pressure that exists, in the dural sinus blood. Colloidal substances pass, slowly and crystalloids are absorbed rapidly., Normally, about 500 mL of CSF is formed everyday, and an equal amount is absorbed., , PRESSURE EXERTED BY, CEREBROSPINAL FLUID, FIGURE 163.1: Composition of cerebrospinal fluid, , SUBSTANCES AFFECTING, THE FORMATION OF CSF, 1. Pilocarpine, ether and extracts of pituitary gland, stimulate the secretion of CSF by stimulating, choroid plexus, 2. Injection of isotonic saline also stimulates CSF, formation, 3. Injection of hypotonic saline causes greater rise in, capillary pressure and intracranial pressure and, fall in osmotic pressure, leading to increase in, CSF formation, 4. Hypertonic saline decreases CSF formation and, decreases the CSF pressure. The increased, intracranial pressure is reduced by injection of, 30% to 35% of sodium chloride or 50% sucrose., , CIRCULATION OF, CEREBROSPINAL FLUID, Major quantity of CSF is formed in lateral ventricles, and enters third ventricle by passing through foramen, of Monro (Figs. 163.2 and 163.3). From here, it passes, to fourth ventricle through aqueductus Sylvius. From, fourth ventricle, CSF enters the cisterna magna and, cisterna lateralis through foramen of Magendie (central, opening) and foramen of Luschka (lateral opening)., From cisterna magna and cisterna lateralis, CSF, circulates through subarachnoid space over spinal, cord and cerebral hemispheres. It also flows into, central canal of spinal cord., , Pressure exerted by CSF in man varies in different, position, viz., Lateral recumbent position : 10 to 18 cm of H2O, Lying position, : 13 cm of H2O, Sitting position, : 30 cm of H2O, Certain events like coughing and crying increase, the pressure by decreasing absorption. Compression of, internal jugular vein also raises the CSF pressure., , FUNCTIONS OF CEREBROSPINAL FLUID, 1. Protective Function, CSF acts as fluid buffer and protects the brain from, shock. Since, the specific gravity of brain and CSF is, more or less same, brain floats in CSF. When head, receives a blow, CSF acts like a cushion and prevents, the movement of brain against the skull bone and, thereby, prevents the damage of brain., However, if the head receives a severe blow, the, brain moves forcefully and hits against the skull bone,, leading to the damage of brain tissues. Brain strikes, against the skull bone at a point opposite to the point, where the blow was applied. So, this type of damage, to the brain is known as countercoup injury., 2. Regulation of Cranial Content Volume, Regulation of cranial content volume is essential, because, brain may be affected if the volume of cranial, content increases. It happens in cerebral hemorrhage, and brain tumors., Increase in cranial content volume is prevented, by greater absorption of CSF to give space for the, increasing cranial contents.
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Chapter 163 t Cerebrospinal Fluid (CSF) 951, , FIGURE 163.2: Circulation of cerebrospinal fluid, , 3. Medium of Exchange, CSF is the medium through which many substances,, particularly nutritive substances and waste materials, are exchanged between blood and brain tissues., , COLLECTION OF CEREBROSPINAL FLUID, CSF is collected either by cisternal puncture or lumbar, puncture. In cisternal puncture, the CSF is collected, by passing a needle between the occipital bone and, atlas, so that it enters cisterna magna. In lumbar, puncture, the lumbar puncture needle is introduced, into subarachnoid space in lumbar region, between, the third and fourth lumbar spines., , back of the subject by joining the highest points of, , iliac crests of both sides. Opposite to midplane, this, , line crosses the fourth lumbar spine., After determining the area of fourth lumbar, spine, third lumbar spine is palpated. The needle, is introduced into subarachnoid space by passing, through soft tissue space between the two spines., Reasons for selecting this site, 1. Spinal cord will not be injured, because, it, terminates below the lower border of the first, lumbar vertebra. Cauda equina may be damaged., But it is regenerated., 2. Subarachnoid space is wider in this site. It is, because the pia mater is reduced very much., , LUMBAR PUNCTURE, Uses of Lumbar Puncture, Posture of Body for Lumbar Puncture, The reclining body is bent forward, so as to flex the, vertebral column as far as possible. Then the body is, brought near edge of a table. The highest point of iliac, crest is determined by palpation. A line is drawn on the, , Lumbar puncture is used for:, 1. Collecting CSF for diagnostic purposes, 2. Injecting drugs (intrathecal injection) for spinal, anesthesia, analgesia and chemotherapy, 3. Measuring the pressure exerted by CSF.
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952 Section 10 t Nervous System, In capillaries of other organs, adjacent endothelial, cells leave the cleft called fenestra, which allows, transcytosis of several substances through endothelium, (Chapter 111). However, in capillaries of brain, fenestra, are absent because, the endothelial cells fuse with each, other by tight junctions (Fig. 163.4)., Tight junctions are formed between endothelial, cells of the capillaries at childhood. At the same time,, cytoplasmic foot processes of astrocytes (neuroglial, cells) develop around capillaries and reinforce the, barrier. Astocytes envelop the vasculature almost, completely., Pericytes also form the important cellular, constituent of BBB. These cells play an important role, in formation and maintenance of tight junction and, structural stability of the barrier. In brain, pericytes, function as macrophages and play an important role in, the defense., FUNCTIONS OF BLOOD-BRAIN BARRIER, BBB acts as both a mechanical barrier and transport, mechanisms. It prevents potentially harmful chemical, substances and permits metabolic and essential, materials into the brain tissues. By preventing injurious, materials and organisms, BBB provides healthy, environment for the nerve cells of brain., Substances which can Pass through, Blood-Brain Barrier, FIGURE 163.3: Cerebrospinal fluid circulation, , BLOOD-BRAIN BARRIER, Blood-brain barrier (BBB) is a neuroprotective structure, that prevents the entry of many substances and, pathogens into the brain tissues from blood., It was observed more than 50 years ago, that, when trypan blue, the acidic dye was injected into, living animals, all the tissues of body were stained by, it, except the brain and spinal cord. This observation, suggested that there was a hypothetical barrier, which, prevented the diffusion of trypan blue into the brain, tissues from the capillaries. This barrier was named, as blood-brain barrier (BBB). It exists in the capillary, membrane of all parts of the brain, except in some, areas of hypothalamus., STRUCTURE OF BLOOD-BRAIN BARRIER, Tight junctions in the endothelial cells of brain capillaries, are responsible for BBB mechanism., , 1., 2., 3., 4., 5., 6., 7., , Oxygen, Carbon dioxide, Water, Glucose, Amino acids, Electrolytes, Drugs such as L-dopa, 5-hydroxytryptamine sulfonamides, tetracycline and many lipid-soluble drugs, 8. Lipid-soluble anesthetic gases such as ether and, nitrous oxide, 9. Other lipid-soluble substances., Substances which cannot Pass through, Blood-Brain Barrier, 1. Injurious chemical agents, 2. Pathogens such as bacteria, 3. Drugs such as Penicillin and the catecholamines., Dopamine also cannot pass through BBB. So,, parkinsonism is treated with L-dopa, instead of, dopamine.
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Chapter 163 t Cerebrospinal Fluid (CSF) 953, , FIGURE 163.4: Blood-brain barrier, , 4. Bile pigments: However, since the barrier is not well, developed in infants, the bile pigments enter the, brain tissues. During jaundice in infants, the bile, pigments enter brain and causes damage of basal, ganglia, leading to kernicterus (refer Chapter 21, for details)., , BLOOD-CEREBROSPINAL, FLUID BARRIER, Blood-CSF barrier is the barrier between blood and, cerebrospinal fluid that exists at the choroid plexus., The function of this barrier is similar to that of BBB. It, does not allow the movement of many substances from, blood to cerebrospinal fluid. It allows the movement of, only those substances which are allowed by BBB., , APPLIED PHYSIOLOGY –, HYDROCEPHALUS, Abnormal accumulation of CSF in the skull, associated, with enlargement of head is called hydrocephalus., During obstruction of any foramen, through which CSF, escapes, the ventricular cavity dilates and this condition, is called internal hydrocephalus. It is also known as, non-communicating hydrocephalus., On the other hand, if the arachnoid villi are blocked,, external or communicating hydrocephalus occurs., Hydrocephalus along with increased intracranial, pressure causes headache and vomiting. In severe, conditions, it leads to atrophy of brain, mental weakness, and convulsions.
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Autonomic Nervous, System (ANS), , , , , , , , , , , , Chapter, , 164, , INTRODUCTION, SYMPATHETIC DIVISION, PARASYMPATHETIC DIVISION, FUNCTIONS, NEUROTRANSMITTERS, SYMPATHOMIMETIC DRUGS, SYMPATHETIC BLOCKERS, PARASYMPATHOMIMETIC DRUGS, PARASYMPATHETIC BLOCKERS, GANGLIONIC BLOCKERS, , INTRODUCTION, Autonomic nervous system (ANS) is primarily, concerned with regulation of visceral or vegetative, functions of the body. So, it is also called vegetative, or involuntary nervous system., DIVISIONS OF ANS, From anatomical and physiological point of view, ANS is, divided into two divisions:, 1. Sympathetic division, 2. Parasympathetic division., Differences and comparison between both the divi, sions of ANS are given in Tables 164.1 and 164.2., , SYMPATHETIC DIVISION, Sympathetic division is otherwise called thoracolumbar, outflow because, the preganglionic neurons are, situated in lateral gray horns of 12 thoracic and first two, lumbar segments of spinal cord. Fibers arising from, here are known as preganglionic fibers. Preganglionic, fibers leave the spinal cord through anterior nerve, root and white rami communicantes and terminate in, the postganglionic neurons, which are situated in the, sympathetic ganglia., , Sympathetic division supplies smooth muscle fibers, of all the visceral organs such as blood vessels, heart,, lungs, glands, gastrointestinal organs, etc., SYMPATHETIC GANGLIA, Ganglia of sympathetic division are classified into three, groups:, A. Paravertebral or sympathetic chain ganglia, B. Prevertebral or collateral ganglia, C. Terminal or peripheral ganglia., A. Paravertebral or Sympathetic Chain Ganglia, Paravertebral or sympathetic chain ganglia are, arranged in a segmental fashion along the anterolateral, surface of vertebral column. Ganglia on either side, of the spinal cord are connected with each other by, longitudinal fibers, to form the sympathetic chains (Fig., 164.1). Both the chains extend from skull to coccyx., Ganglia of the sympathetic chain (trunk) on each, side are divided into four groups:, 1. Cervical ganglia : 8 in number, 2. Thoracic ganglia : 12 in number, 3. Lumbar ganglia : 5 in number, 4. Sacral ganglia, : 5 in number.
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Chapter 164 t Autonomic Nervous System (ANS) 955, TABLE 164.1: Actions of sympathetic and parasympathetic divisions of autonomic nervous system, Effector organ, , Sympathetic division, , Parasympathetic division, , Ciliary muscle, , Relaxation, , Contraction, , Pupil, , Dilatation, , Constriction, , 2. Lacrimal glands, , Decrease in secretion, , Increase in secretion, , 3. Salivary glands, , Decrease in secretion and, vasoconstriction, , Increase in secretion and, vasodilatation, , Motility, , Inhibition, , Acceleration, , Secretion, , Decrease, , Increase, , Sphincters, , Constriction, , Relaxation, , Smooth muscles, , Relaxation, , Contraction, , Relaxation, , Contraction, , Detrusor muscle, , Relaxation, , Contraction, , Internal sphincter, , Constriction, , Relaxation, , 7. Sweat glands, , Increase in secretion, , –, , 8. Heart – rate and force, , Increase, , Decrease, , 9. Blood vessels, , Constriction of all blood vessels,, except those in heart and skeletal Dilatation, muscle, , 1. Eye, , 4. Gastrointestinal tract, , 5. Gallbladder, 6. Urinary bladder, , 10. Bronchioles, , Dilatation, , 1. Cervical ganglia, Eight cervical ganglia are arranged in three groups:, i. Superior cervical ganglion: It is formed by, the fusion of upper four cervical ganglia. It, is the largest ganglion of ANS. It receives, preganglionic fibers from first thoracic spinal, segment (T1) via white rami. Postganglionic, fibers from this ganglion, supply the blood, vessels, glands, etc. Superior cervical ganglion, also sends some fibers to heart through superior, cervical sympathetic nerve and cardiac plexus., ii. Middle cervical ganglion: It is formed by fifth, and sixth cervical ganglia. Preganglionic fibers, arise from T1 segment. Postganglionic fibers, from here supply the sweat glands, thyroid, gland and parathyroid glands. It also sends, fibers to heart via middle cervical sympathetic, nerve and cardiac plexus., iii. Inferior cervical ganglion: This ganglion is, formed by the fusion of seventh and eighth, cervical ganglia. First thoracic ganglion fuses, with inferior cervical ganglion, forming stellate, ganglion. It receives preganglionic fibers from, T1 segment. It sends postganglionic fibers, to heart through inferior cervical sympathetic, , Constriction, , nerve and cardiac plexus. Postganglionic, fibers also form the plexus around subclavian, artery and its branches., 2. Thoracic ganglia, There are 12 thoracic ganglia on each side and these, ganglia are evenly spaced. Thoracic ganglia receive, preganglionic fibers from the thoracic segments of, spinal cord. Postganglionic fibers from thoracic ganglia, are distributed to visceral organs in the thorax and, abdomen., , 3. Lumbar ganglia, There are 5 lumbar ganglia. Preganglionic fibers for, these ganglia arise from first and second lumbar spinal, segments (L1 and L2) and reach the lumbar ganglia., From here, the fibers extend down to sacral ganglia, also. Postganglionic fibers from these ganglia supply, the abdominal and pelvic organs., 4. Sacral ganglia, There are 5 sacral ganglia, which receive the pregang, lionic fibers from L1 and L2 segments. Postganglionic, fibers from sacral ganglia innervate the blood vessels, and sweat glands in the lower limb.
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956 Section 10 t Nervous System, , FIGURE 164.1: Autonomic nervous system
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Chapter 164 t Autonomic Nervous System (ANS) 957, TABLE 164.2: Classical comparison of sympathetic and parasympathetic divisions of autonomic nervous system, Features, , Sympathetic division, , Parasympathetic division, , 1. Location of preganglionic neuron, , Thoracolumbar segments of spinal cord, , Nuclei of III, VII, IX and X cranial nerves, and sacral (S2 to S4) segments of, spinal cord, , 2. Location of postganglionic neuron, , Away from target organ, , Near or in the target organ, , 3. Length of preganglionic fibers, , Relatively short, , Relatively long, , 4. Length of postganglionic fibers, , Relatively long, , Relatively short, , 5. Preganglionic neurotransmitter, , Acetylcholine, , Acetylcholine, , 6. Postganglionic neurotransmitter, , Noradrenaline, , Acetylcholine, , Below the sacral level, both the sympathetic, trunks converge and fuse upon the anterior surface, of coccyx and form a terminal swelling. This terminal, swelling is known as coccygeal ganglion. Unpaired, coccygeal ganglion is also called ganglion impar. It, receives preganglionic fibers from L1 and L2 segments., Postganglionic fibers from here are distributed to the, abdominal viscera and pelvic region., B. Prevertebral or Collateral Ganglia, Prevertebral ganglia are situated in thorax, abdomen, and pelvis, in relation to aorta and its branches., Prevertebral ganglia are:, 1. Celiac ganglion, 2. Superior mesenteric ganglion, 3. Inferior mesenteric ganglion., Prevertebral ganglia receive preganglionic fibers, from T5 to L2 segments. Postganglionic fibers from, these ganglia supply the visceral organs of thorax,, abdomen and pelvis., C. Terminal or Peripheral Ganglia, Terminal ganglia are situated within or close to structures, innervated by them. Heart, bronchi, pancreas and, urinary bladder are innervated by the terminal ganglia., Sympathoadrenergic System, Sympathoadrenergic system is a functional and phylo, genetic unit that includes sympathetic division, and adrenal medulla. Adrenal medulla is a modified, sympathetic ganglion. Since adrenal medulla and, sympathetic division develop from the same neural crest,, their secretions and functions are almost the same. Any, increase in sympathetic activity increases the secretion of, catecholamines from adrenal medulla (refer Chapter 71)., , PARASYMPATHETIC DIVISION, Parasympathetic division of ANS is otherwise called the, craniosacral outflow because, the fibers of this division, arise from brain and sacral segments of spinal cord., , CRANIAL OUTFLOW OR CRANIAL PORTION, OF PARASYMPATHETIC DIVISION, Cranial outflow or cranial portion of parasympathetic, division arises from brainstem. It innervates the, blood vessels of head and neck and many, thoracoabdominal visceral organs. Cranial outflow, includes the following cranial nerves:, 1. Oculomotor (III) nerve, 2. Facial (VII) nerve, 3. Glossopharyngeal (IX) nerve, 4. Vagus (X) nerve., Preganglionic fibers of these cranial nerves arise, from neurons situated at two different levels:, 1. Tectal or midbrain outflow (III cranial nerve), 2. Bulbar level or bulbar outflow (VII, IX and X cranial, nerves)., Preganglionic fibers are longer and reach the, postganglionic neurons, which are situated within the, organs or close to the organs innervated by these, nerves. Preganglionic fibers are myelinated, but the, postganglionic fibers are non-myelinated., 1. Tectal or Midbrain Outflow, Group of cells forming Edinger-Westphal nucleus of, III cranial nerve gives rise to tectal fibers. Fibers from, this nucleus end in ciliary ganglion. Postganglionic, fibers from here supply the sphincter pupillae and ciliary, muscle., 2. Bulbar Level or Bulbar Outflow, Preganglionic fibers are the fibers of VII, IX and X, cranial nerves, which arise from the nuclei present in, the medulla oblongata., Fibers of VII cranial nerve supply the lacrimal, nasal,, submaxillary and sublingual glands. Preganglionic, fibers of this nerve end in sphenopalatine ganglion, and submaxillary ganglion. Postganglionic fibers, from sphenopalatine ganglion supply lacrimal and, nasal glands. Postganglionic fibers from submaxillary, ganglion supply sublingual and submaxillary glands.
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958 Section 10 t Nervous System, Fibers of IX cranial nerve supply the parotid gland., Preganglionic fibers synapse with neurons of otic, ganglion. Postganglionic fibers from otic ganglion supply, the parotid gland., Fibers of X cranial nerve supply visceral organs of, the body. Preganglionic fibers terminate in the ganglia,, which are situated on or near the organs. Postganglionic, fibers from the ganglia supply the organs. Vagus, nerve supplies almost all the organs in the thorax and, abdomen, but not the pelvic organs., SACRAL OUTFLOW OR SACRAL PORTION, OF PARASYMPATHETIC DIVISION, Sacral outflow or sacral portion of parasympathetic, division arises from the sacral segments of spinal, cord. It innervates smooth muscles forming the walls, of viscera and the glands such as large intestine, liver,, spleen, kidneys, bladder, genitalia, etc., Preganglionic fibers arise from anterior gray horn, cells of 2nd, 3rd and 4th (from 1st also in some cases), sacral segments of spinal cord and form the pelvic, nerve (nervi erigens). Fibers end on postganglionic, neurons, which are situated on or near the visceral, organs. Fibers from postganglionic neurons supply, descending colon, rectum, urinary bladder, internal, sphincter, urethra and accessory sex organs., Sacral parasympathetic fibers supply those, visceral organs which are not supplied by vagus., , FUNCTIONS OF ANS, Autonomic nervous system is concerned with the, regulation of functions, which are beyond voluntary, control. By controlling the various vegetative functions,, ANS plays an important role in maintaining constant, internal environment (homeostasis)., Almost all the visceral organs are supplied by both, sympathetic and parasympathetic divisions of ANS, and the two divisions produce antagonistic effects on, each organ. When the fibers of one division supplying, to an organ is sectioned or affected by lesion, the, effects of fibers from other division on the organ, become more prominent., Actions of the sympathetic and parasympathetic, fibers on various structures are given in Table 164.1., , NEUROTRANSMITTERS OF ANS, Different nerve fibers of ANS execute the functions, by releasing some neurotransmitter substances, (Table 164.2)., , SYMPATHETIC FIBERS, 1. Preganglionic fibers: Acetylcholine (Ach), 2. Postganglionic noradrenergic fibers: Noradrenaline, 3. Postganglionic cholinergic fibers: Ach, Postganglionic sympathetic cholinergic nerve fibers, supply sweat glands and blood vessels in heart and in, skeletal muscle., PARASYMPATHETIC FIBERS, 1. Preganglionic fibers: Ach, 2. Postganglionic fibers: Ach, Catecholamines, Synthesis and the metabolism of catecholamines are, explained in Chapter 71., Acetylcholine, Refer Chapter 141 for details of acetylcholine., Receptors of Neurotransmitter, Adrenergic receptors: Details are given in Chapter 71., Acetylcholine receptors: Details are given in Chapter, 141., , SYMPATHOMIMETIC DRUGS, Sympathomimetic drugs or adrenaline-like drugs are, the drugs, which produce the effects of sympathetic, stimulation. Adrenaline and noradrenaline produced, in the body act only for a short duration of about 1 to, 2 minutes. Whereas, sympathomimetic drugs injected, intravenously act for a longer period of about 30 minutes, to 2 hours. Sympathomimetic drugs are:, Drugs Stimulating the Receptors Directly, 1. Phenylephrine (alpha receptors), 2. Isoproterenol (beta receptors), 3. Albuterol (beta2 receptors)., Drugs Inducing the Release of Noradrenaline, 1. Ephedrine, 2. Tyramine, 3. Amphetamine., , SYMPATHETIC BLOCKERS, Sympathetic blockers are the drugs that prevent, actions of sympathetic neurotransmitter. Sympathetic, blockers act on all levels. Actions of blocking agents, are given in Table 164.3.
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Chapter 164 t Autonomic Nervous System (ANS) 959, TABLE 164.3: Actions of sympathetic blocking agents, Blocking agent, , Action, , 1. Reserpine, , Prevention of synthesis and storage of noradrenaline, , 2. Quanethidine, , Prevention of release of noradrenaline, , 3. Phenoxybenzamine, , Blockage of alpha adrenergic receptors, , 4. Phentolamine, , Blockage of alpha adrenergic receptors, , 5. Metaprolal, , Blockage of beta adrenergic receptors, , 6. Hexamethonium, , Blockage of transmission of nerve impulse through sympathetic ganglia, , PARASYMPATHOMIMETIC DRUGS, , PARASYMPATHETIC BLOCKERS, , Parasympathomimetic drugs or Achlike drugs are, drugs, which produce the effects of parasympathetic, stimulation. Ach produced in the body acts only for a, short period, whereas the injected Ach acts for a long, time. Similarly, parasympathomimetic drugs also exhibit, their actions for a longer time. Parasympathomimetic, drugs are:, , Parasympathetic blockers are drugs, which prevent the, actions of parasympathetic neurotransmitter. The drugs, atropine, homatropine and scopolamine inhibit the, actions of Ach by blocking the muscarinic receptors., , 1. Drugs which Act on Muscarinic Receptors, Pilocarpine and methacholine produce their effects by, acting on the muscarinic receptors., , 2. Drugs which Prolong the Action of Ach, Action of Ach can be prolonged by preventing its, destruction. Drugs like neostigmine and physostigmine, inhibit the activity of acetylcholinesterase and so the Ach, is not destroyed quickly., , GANGLIONIC BLOCKERS, Ganglionic blockers are the drugs that prevent the, transmission of impulses from preganglionic neurons, to postganglionic neurons. Tetraethyl ammonium, ion, hexamethonium ion and pentolinium are some, of the ganglionic blockers. These drugs block both, sympathetic and parasympathetic ganglia. However,, ganglionic blockers are commonly used to block, sympathetic ganglia, rather than the parasympathetic, ganglia because sympathetic blockade overshadows, the parasympathetic blockade.
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960 Questions in Nervous System, , QUESTIONS IN NERVOUS SYSTEM, , LONG QUESTIONS, 1. What is neuron? Describe the structure of neuron, and the properties of nerve fibers., 2. What are receptors? Classify them and explain, their properties., 3. What is synapse? Explain the structure, functions, and properties of synapse., 4. Define and classify reflex action. Explain reflex, arc and the properties of reflexes., 5. Name the ascending tracts of the spinal cord and, explain spinothalamic tracts., 6. What are the tracts of spinal cord? Describe the, spinocerebellar tracts., 7. Give an account of tracts in the posterior white, funiculus of spinal cord., 8. Enumerate the descending tracts of spinal cord., Describe in detail the pyramidal tracts. Write, a note on the effects of upper and lower motor, neuron lesions., 9. Write in detail, about the effects of complete and, incomplete transection of spinal cord., 10. What are the thalamic nuclei? Describe the, connections, functions and effects of lesions of, thalamus., 11. Name the hypothalamic nuclei. Explain the, connections, functions and effects of lesions of, hypothalamus., 12. Explain the different parts of cerebellum?, Enumerate the functions of cerebellum. Write a, note on cerebellar lesions., 13. Explain the connections, functions and effects of, lesions of corticocerebellum (neocerebellum)., 14. Explain the connections, functions and effects of, lesions of spinocerebellum (paleocerebellum)., 15. Explain the connections, functions and effects of, lesions of vestibulocerebellum (archicerebellum)., 16. What are the components of basal ganglia?, Give an account of connections, functions and, disorders of basal ganglia., 17. What are the various lobes of cerebral cortex?, Describe their functions. Add a note on frontal, lobe syndrome., 18. Classify the components of limbic system. Explain, the functions of limbic system., 19. What is reticular formation? Describe the connec, tions and the functions of reticular formation., 20. Give an account of postural reflexes., 21. Explain the role of vestibular apparatus in the, maintenance of equilibrium., , SHORT QUESTIONS, 1., 2., 3., 4., 5., 6., 7., 8., 9., 10., 11., 12., 13., 14., 15., 16., 17., 18., 19., 20., 21., 22., 23., 24., 25., 26., 27., 28., 29., 30., 31., 32., 33., 34., 35., 36., 37., 38., 39., 40., 41., 42., 43., 44., 45., 46., 47., , Structure of neuron., Myelin sheath., Neurotrophins., Nerve growth factor., Classification of nerve fibers., Properties of nerve fibers., Action potential in nerve fiber., Voltage clamping., Saltatory conduction., Degeneration of nerve fiber., Wallerian degeneration., Regeneration of nerve fiber., Neuroglia., Exteroceptors., Mechanoceptors., Generator (receptor) potential., Sensory transduction., Synapse., Synaptic transmission., Synaptic inhibition/IPSP., Synaptic potentials/EPSP., Neurotransmitters., Neuromodulators., Opioid peptides., Reflex arc., Properties of reflexes., Superficial reflexes., Deep reflexes., Babinski sign., Spinothalamic tracts., Spinocerebellar tracts., Tracts of Goll and Burdach., Pyramidal tracts., Extrapyramidal tracts., Upper motor neuron lesion., Lower motor neuron lesion., Complete transection of spinal cord., Incomplete transection of spinal cord., BrownSèquard syndrome/Hemisection of spinal, cord., Syringomyelia., Tabes dorsalis., Pathway for fine touch sensations., Pathway for pressure sensation., Pathway for temperature sensations., Pathway for conscious kinesthetic sensations., Pathway for subconscious kinesthetic sensations., Pathway for pain sensations.
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Questions in Nervous System 961, 48., 49., 50., 51., 52., 53., 54., 55., 56., 57., 58., 59., 60., 61., 62., 63., 64., 65., 66., 67., 68., 69., 70., 71., 72., 73., 74., 75., 76., 77., 78., 79., , Pain sensation., Referred pain., Gate theory., Functions of thalamus., Thalamic lesions., Internal capsule., Functions of hypothalamus., Regulation of food intake., Disorders of hypothalamus., Rage and sham rage., Corticocerebellum (neocerebellum)., Spinocerebellum (paleocerebellum)., Corpus striatum., Red nucleus., Functions of basal ganglia., Effects of lesions of basal ganglia., Parkinson disease., Prefrontal lobe of cerebral cortex., Motor areas of cerebral cortex., Frontal lobe of cerebral cortex., Parietal lobe (or sensory areas) of cerebral, cortex., Frontal lobe syndrome., KlüverBucy syndrome., Localization of cortical connections., Papez circuit., Functions of limbic system., ARAS., Decerebrate rigidity., Proprioceptors., Muscle spindle., Stretch reflex., Reciprocal innervation., , 80., 81., 82., 83., 84., 85., 86., 87., 88., 89., 90., 91., 92., 93., 94., 95., 96., 97., 98., 99., 100., 101., 102., 103., 104., 105., 106., 107., 108., 109., 110., , Crossed extensor reflex., Clasp-knife reflex., Righting reflexes., Semicircular canal., Otolith organ., Crista ampullaris., Effects of stimulation of semicircular canals., Nystagmus., Motion sickness., EEG., Epilepsy., EEG pattern during sleep., Physiological changes during sleep., REM and nonREM sleep., Sleep disorders., Learning., Memory., Classical conditioned reflexes., Properties of conditioned reflexes., Speech., Speech disorders., Aphasia., CSF., Bloodbrain barrier., Craniosacral outflow., Thoracolumbar outflow., Role of ANS in the regulation of cardiovascular, functions., Role of ANS in the regulation of gastrointestinal, activity., Neurotransmitters of ANS., Functions of sympathetic division of ANS., Functions of parasympathetic division of ANS.
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Section, , 11, , 165., 166., 167., 168., 169., 170., 171., 172., 173., 174., 175., 176., 177., , Special Senses, , Structure of the Eye ................................................................................ 965, Visual Process......................................................................................... 978, Field of Vision .......................................................................................... 987, Visual Pathway ........................................................................................ 989, Pupillary Reflexes ................................................................................... 994, Color Vision ............................................................................................. 999, Errors of Refraction ............................................................................... 1004, Structure of Ear ..................................................................................... 1007, Auditory Pathway .................................................................................. 1013, Mechanism of Hearing .......................................................................... 1016, Auditory Defects .................................................................................... 1022, Sensation of Taste ................................................................................. 1024, Sensation of Smell ................................................................................ 1028
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Structure of the Eye, SPECIAL SENSES, FUNCTIONAL ANATOMY OF THE EYEBALL, , , , , , , MORPHOLOGY, ORBITAL CAVITY, EYELIDS, CONJUNCTIVA, LACRIMAL GLAND AND TEAR, , WALL OF THE EYEBALL, , , , , OUTER LAYER, MIDDLE LAYER, INNER LAYER, , FUNDUS OCULI, , , , OPTIC DISK – BLIND SPOT, MACULA LUTEA, , INTRAOCULAR FLUID, , , , VITREOUS HUMOR, AQUEOUS HUMOR, , INTRAOCULAR PRESSURE, LENS, , , , STRUCTURE, CHANGES IN THE LENS DURING OLD AGE, , OCULAR MUSCLES, , , , MUSCLES OF THE EYEBALL, INNERVATION OF OCULAR MUSCLES, , OCULAR MOVEMENTS, , , , , , MOVEMENTS IN VERTICAL AXIS, MOVEMENTS IN TRANSVERSE AXIS, MOVEMENTS IN ANTEROPOSTERIOR AXIS, SIMULTANEOUS MOVEMENTS OF BOTH EYES, , APPLIED PHYSIOLOGY, , , , GLAUCOMA, CATARACT, , Chapter, , 165
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966 Section 11 t Special Senses, , SPECIAL SENSES, Special senses or special sensations are the complex, sensations which involve specialized sense organs., These sensations are different from somatic sensations, that arise from skin, muscles, tendons and joints, (Chapter 144)., Special senses are:, 1. Sensation of vision, 2. Sensation of hearing, 3. Sensation of taste, 4. Sensation of smell., , FUNCTIONAL ANATOMY, OF THE EYEBALL, , to anterior pole and fovea centralis, situated lateral to, posterior pole is known as visual axis. Light rays pass, through the visual axis of eyeball (Fig. 165.1). Optic, nerve leaves the eye, little medial to posterior pole., ORBITAL CAVITY, Except anterior one sixth, the eyeball is situated in a, bony cavity known as orbital cavity or eye socket. A, thick layer of areolar tissue is interposed between bone, and eyeball. It serves as a cushion to protect the eyeball, from external force. Eyeballs are attached to orbital, cavity by the ocular muscles., EYELIDS, , MORPHOLOGY, Human eyeball (bulbus oculi) is approximately globe, shaped, with a diameter of about 24 mm. It is slightly, flattened from above downwards. Eyeball is made, up of two segments, an anterior part and a posterior, part. Anterior part is small and forms one sixth of the, eyeball. Posterior part is larger and forms five sixth of, the eyeball. Radius of this part is about 8 mm. Posterior, wall of this part is lined by the light-sensitive structure, called retina., Center of anterior curvature of the eyeball is called, anterior pole and the center of posterior curvature is, called posterior pole. Line joining both the poles is called, optic axis. The line joining a point in cornea, little medial, , Eyelids protect the eyeball from foreign particles coming, in contact with its surface and cutoff the light during, sleep. Eyelids are opened and closed voluntarily, as, well as by reflex action., Margins of eyelids have sensitive hair called the cilia., Each cilium arises from a follicle, which is surrounded, by a sensory nerve plexus. When dust particle comes, in contact with cilia, these sensory nerves are activated,, resulting in rapid blinking of eyelids. It prevents the dust, particles from reaching the eyeball. There are about, 100 to 150 cilia in the upper eyelid and about 50 to 75, cilia in the lower eyelid. Meibomian glands and some, sebaceous glands are also found in the eyelids. These, glands open into the follicles of cilia. Infection of these, glands leads to the development of common eye sty., , FIGURE 165.1: Optical and visual axis
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Chapter 165 t Structure of the Eye 967, Opening between the two eyelids is called, , palpebral fissure. In adults, it is about 25 mm long., , Its width is about 12 mm to 15 mm, when opened., CONJUNCTIVA, , Conjunctiva is a thin mucus membrane, which covers, the exposed part of eye. After covering the anterior, surface, conjunctiva is reflected into the inner surfaces, of eyelids. Part of conjunctiva covering the eyeball is, called bulbar portion. Part covering the eyelid is called, palpebral portion. During closure or opening of eyelids,, the opposed portions of conjunctiva slide over each, other. Surface of conjunctiva is lubricated by thin film of, tear secreted by lacrimal gland., , WALL OF THE EYEBALL, Wall of the eyeball is composed of three layers:, A. Outer layer, which includes cornea and sclera, B. Middle layer, which includes choroid, ciliary body, and iris, C. Inner layer, the retina., OUTER LAYER OR TUNICA EXTERNA, OR TUNICA FIBROSA, Outer layer preserves the shape of the eyeball., Posterior five sixth of this coat is opaque and it is, called the sclera. Anterior one sixth is transparent and, is known as cornea., 1. Sclera, , LACRIMAL GLAND AND TEAR, Lacrimal gland is situated in the shelter of bone,, forming upper and outer border of wall of the eye, socket. From lacrimal gland, tear flows over the, surface of conjunctiva and drains into nose via lacrimal, ducts, lacrimal sac and nasolacrimal duct. Tear, is a hypertonic fluid. Due to its continuous washing, and lubrication, the conjunctiva is kept moist and is, protected from infection. Tear also contains lysozyme, that kills bacteria. Secretion of tears is controlled by the, parasympathetic fibers of facial (VII cranial) nerve., , Sclera is the tough white fibrous outer layer of eyeball,, that covers posterior five sixth of the eye. Anteriorly it, is continuous with cornea (Fig. 165.2)., Sclera is formed by white fibrous tissues and elastic, fibers. Posterior part of sclera, where it is pierced by, the optic nerve is thin with perforations. It is named as, lamina cribrosa., , 2. Cornea, Cornea is the transparent convex anterior portion of the, outer layer of eyeball, which covers the iris and pupil., , FIGURE 165.2: Structure of eyeball
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968 Section 11 t Special Senses, It forms the anterior one sixth of outer layer and it is, continuous with sclera., Though cornea is transparent, it does not appear, transparent. It appears in different colors such as blue,, green, brown, grey and black. It is because of the color, of iris, which is present just behind the cornea. Sclera, overlaps cornea at its periphery and appears in front, as white of the eye. Diameter of cornea is about 12 mm, horizontally and 11 mm vertically., Cornea is formed by five layers:, i. Layer of stratified epithelium, ii. Bowman membrane or anterior elastic lamina, iii. Substantia proper, iv. Descemet layer or posterior elastic lamina, v. Layer of endothelial cells., Cornea has a refractory index of 1.376. It is very, sensitive to pain, touch, pressure and cold. Center, of cornea is more sensitive to pain because of rich, supply of free nerve endings. Normally, cornea is not, vascularized. Therefore, it derives its nourishment mainly, from aqueous humor. However, in some pathological, conditions, cornea becomes vascularized., The transitional part of outer layer between sclera, and cornea is called limbus. It is about 1 mm width., Blood vessels are seen only at the limbus. These blood, vessels form superficial marginal plexus in limbus., MIDDLE LAYER OR TUNICA MEDIA, OR TUNICA VASCULOSA, Middle layer surrounds the eyeball completely, except, for a small opening in front known as pupil., This layer comprises of three structures:, 1. Choroid, 2. Ciliary body, 3. Iris., 1. Choroid, Choroid is the thin vascular layer of eyeball situated, between sclera and retina. It forms posterior five sixth, of middle layer. Choroid is extended anteriorly up to, the insertion of ciliary muscle (the level of ora serrata)., Choroid is separated from sclera by perichoroidal, space. Anteriorly, this space is limited by the insertion, of ciliary muscle into sclera. Posteriorly, this space, ends at a short distance from the optic nerve. Inner, surface of choroid faces the pigment epithelium, (innermost layer) of retina., Choroid is composed of rich capillary plexus,, numerous small arteries and veins., , 2. Ciliary Body, Ciliary body is the thickened anterior part of middle layer, of eye, situated between choroid and iris. It is situated, in front of ora serrata. It is in the form of a ring. Its outer, surface is separated from sclera by perichoroidal space., Inner surface of ciliary body faces the vitreous body and, lens. Suspensory ligaments from the lens are attached, to the ciliary body. Anterior surface of ciliary body faces, towards the center of cornea. From the surface, the iris, arises (Fig. 165.3)., Ciliary body has three parts:, i. Orbiculus ciliaris: It is continuous with choroid, and it forms the posterior two third of ciliary, body. It is about 4 mm broad., ii. Ciliary body proper: It is made up of two sets, of ciliary muscles, namely outer longitudinal, and inner circular muscles. Ciliary muscles are, innervated by the parasympathetic fibers of, oculomotor nerve., iii. Ciliary processes: Ciliary processes are the, finger-like projections from inner surface of ciliary, body. There are about 70 ciliary processes,, projecting towards the central axis of eye to, form radial fringes called corona ciliaris., 3. Iris, Iris is a thin colored curtain-like structure of eyeball,, located in front of the lens. It forms a thin circular, diaphragm with a circular opening in the center called, pupil., , Iris is formed by muscles:, i. Constrictor pupillae or iris sphincter muscle, or pupillary constrictor muscle: It is formed by, circular muscle fibers. Contraction of this muscle, causes constriction of pupil., ii. Dilator pupillae or pupillary dilator muscle: It, is formed by radial muscle fibers. Contraction of, this muscle causes dilatation of pupil., Activities of these muscles increase or decrease, the diameter of pupil and regulate the amount of light, entering the eye. Thus, iris acts like the diaphragm of, a camera., Iris separates the space between cornea and lens, into two chambers, namely anterior and posterior, chambers. Both the chambers communicate with each, other through pupil. Lateral border of anterior chamber, is angular in shape. It is called iris angle or angle of, anterior chamber.
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Chapter 165 t Structure of the Eye 969, , FIGURE 165.3: Wall of the eyeball, , INNER LAYER OR TUNICA INTERNA, OR TUNICA NERVOSA OR RETINA, Retina is a delicate light-sensitive membrane that forms, the innermost layer of eyeball. It extends from the, margin of optic disk to just behind ciliary body. Here,, it ends abruptly as a dentated border known as ora, serrata. Retina has the receptors of vision. Structurally,, retina is made up of 10 layers (Fig. 165.4)., Layers of retina from outside in:, 1. Layer of pigment epithelium, 2. Layer of rods and cones, 3. External limiting membrane, 4. Outer nuclear layer, 5. Outer plexiform layer, 6. Inner nuclear layer, 7. Inner plexiform layer, 8. Ganglion cell layer, 9. Layer of nerve fibers, 10. Internal limiting membrane., 1. Layer of Pigment Epithelium, Layer of pigment epithelium is the outermost layer, situated adjacent to choroid. It is a single layer of, hexagonal epithelial cells. Outer portion of epithelial, cells (towards choroid), contains nucleus and moderate, number of round pigment granules. Inner portion has, plenty of needle-shaped dark pigment granules. Many, , protoplasmic extensions arise from the inner surface of, cells and pass between rods and cones. Cytoplasmic, processes also contain dark pigment granules. The, pigment present in this layer is a melanin called fuscin., Pigment epithelial layer absorbs light and, prevents reflection of light rays back from retina. If, light rays are reflected back by retina, image becomes, blurred. Epithelial cells store vitamin A (retinol) and, remove the debris from rod cells and cone cells by, phagocytic action., 2. Layer of Rods and Cones, Layer of rods and cones lies between pigment epithelial, layer and external limiting membrane. Rods and cones, are the light-sensitive portions of visual receptor cells,, namely rod cells and cone cells. Receptor cells are, arranged in a parallel fashion and are perpendicular, to the inner surface of the eyeball. Structure of rod cell, and cone cell is explained in the next chapter., 3. External Limiting Membrane, External limiting membrane is a thin layer, formed by, the chief supporting elements of retina called the Müller, fibers., , 4. Outer Nuclear Layer, Outer nuclear layer is formed by the fibers and granules, of rods and cones. Granules of rods and cones contain
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970 Section 11 t Special Senses, , FIGURE 165.4: Layers of retina, , nucleus. Nuclei of rods are smaller and round and the, nuclei of cones are larger and oval in shape., 5. Outer Plexiform Layer, Outer plexiform layer contains reticular meshwork, formed by terminal fibers of rods and cones and dendrites, from bipolar cells, situated in the inner nuclear layer., 6. Inner Nuclear Layer, , 8. Ganglion Cell Layer, Multipolar cells are present in this layer. Some cells, are large and are called giant ganglion cells. Other, cells are smaller called midget ganglion cells. Axons, from ganglion cells are in the inner surface of the, retina. These axons form the optic nerve. Dendrites, of ganglion cells synapse with axons of bipolar cells, in the inner plexiform layer. Retinal blood vessels are, also present in this layer., , Inner nuclear layer contains small oval-shaped,, flattened bipolar cells. Axons of bipolar cells go inside, and synapse with dendrites of ganglionic cells in the, inner plexiform layer. Dendrites synapse with fibers of, rods and cones in the outer plexiform layer. This layer, also contains nuclei of Müller supporting fibers and, some association neurons called horizontal cells and, amacrine cells., , Layer of nerve fibers is formed by non-myelinated, axons of ganglionic cells. After taking origin, the axons, run horizontally to a short distance. Afterwards, the, fibers converge towards the optic disk and form the, optic nerve. Neuroglial cells, Müller cells and retinal, blood vessels are also present in this layer., , 7. Inner Plexiform Layer, , 10. Internal Limiting Membrane, , Inner plexiform layer of retina consists of synapses, between dendrites of ganglionic cells and axons of, bipolar cells. It also contains processes from amacrine, cells., , Internal limiting membrane is the innermost layer of, retina and it separates retina from the vitreous body., It is a hyaline membrane, formed by the opposition of, expanded ends of Müller fibers., , 9. Layer of Nerve Fibers
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Chapter 165 t Structure of the Eye 971, , FUNDUS OCULI, , Foveal Vision and Extrafoveal vision, , Fundus oculi is the posterior part of interior eyeball. It, is also called fundus (Fig. 165.5). In living subjects,, fundus is examined by ophthalmoscope., Fundus has two important structures:, 1. Optic disk, 2. Macula lutea with fovea centralis., , When one looks at an object, eyeballs are directed, towards the object, so that, the image of that object falls, on fovea of each eye and the person can see the object, very clearly. It is known as foveal vision., Vision in other parts of retina is called peripheral or, extrafoveal vision. It is less sensitive and enables the, subject to gain only a dim and an ill-defined impression, of surroundings., Degeneration of macula lutea leads to blindness., , OPTIC DISK – BLIND SPOT, Optic disk is a pale disk, situated near the center of, the posterior wall of eyeball. It is also called optic, papilla. It is formed by the convergence of axons from, ganglion cells, while forming the optic nerve. Optic, disk contains all the layers of retina, except rods and, cones. Therefore, it is insensitive to light, i.e. the object, is not seen if the image falls upon this area. Because, of this, the optic disk is known as blind spot., , INTRAOCULAR FLUID, Intraocular fluid (fluid in eyeball) is responsible for the, maintenance of shape of the eyeball., Intraocular fluid is of two types:, 1. Vitreous humor, 2. Aqueous humor., , MACULA LUTEA, , VITREOUS HUMOR, , Macula lutea is a small yellowish area, situated a, little lateral to the optic disk in retina. It is also called, yellow spot. Yellow color of macula lutea is due to the, presence of a yellow pigment. Macula lutea has fovea, centralis in its center., , Vitreous humor is a viscous fluid present behind lens,, in the space between lens and retina. It is also known, as vitreous body. It is a highly viscous and gelatinous, substance that is formed by a fine fibrillar network of, proteoglycan molecules. Major substances in vitreous, humor are albumin and hyaluronic acid. These, substances enter vitreous body from blood, by means, of diffusion., Vitreous humor helps to maintain the shape of, eyeball., , Fovea Centralis, Fovea centralis is a minute depression in the center, of macula lutea. Here, all the layers of retina are very, thin. Diameter of fovea is only about 0.5 mm. Fovea, is the region of most acute vision because it contains, only cones., , AQUEOUS HUMOR, Aqueous humor is a thin fluid present in front of retina., It fills the space between lens and cornea. This space, is divided into anterior and posterior chambers by, iris. Both the chambers communicate with each other, through pupil., Properties of Aqueous Humor, Volume, Reaction and pH, Viscosity, Refractory index, , :, :, :, :, , 0.13 mL, Alkaline with a pH of 7.5, 1.029, 1.34., , Composition of Aqueous Humor, Composition of aqueous humor is given in Figure 165.6., Formation of Aqueous Humor, FIGURE 165.5: Fundus oculi, , Aqueous humor is formed by ciliary processes. It is, formed from plasma within capillary network of ciliary
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972 Section 11 t Special Senses, Measurement of intraocular pressure is an, important part of eye examination. It is measured, by tonometer. When intraocular pressure increases, to about 60 to 70 mm Hg, glaucoma occurs. Refer, Applied Physiology in this chapter for details., , LENS, Lens of the eyeball is crystalline in nature. It is, situated behind the pupil. It is a biconvex, transparent, and elastic structure. It is avascular and receives its, nutrition mainly from the aqueous humor., Lens refracts light rays and helps to focus the, image of the objects on retina. Focal length of human, lens is 44 mm and its refractory power is 23 D., Lens is supported by the suspensory ligaments, (zonular fibers), which are attached with ciliary bodies., FIGURE 165.6: Composition of aqueous humor, , STRUCTURE OF THE LENS, , process by diffusion, ultrafiltration and active transport, through the epithelial cells lining the ciliary processes., After formation, aqueous humor reaches the posterior, chamber by passing through the suspensory ligaments., From here, it reaches the anterior chamber via pupil., Formation of aqueous humor is a continuous, process. Rate of formation is about 2 to 3 µL per, minute. Amount of aqueous humor in anterior chamber, is about 230 µL to 250 µL and in posterior chamber it, is about 50 µL to 60 µL., , Lens is formed of three components:, 1. Capsule, 2. Anterior epithelium, 3. Lens substance., , Drainage of Aqueous Humor, , Anterior epithelium is a single layer of cuboidal, epithelial cells, situated beneath the capsule. At the, margins, epithelial cells are elongated. Epithelial cells, give rise to lens fibers present in the lens substance., , From anterior chamber, the aqueous humor passes into, the angle between cornea and iris called limbus. From, here, it passes through meshwork of trabeculae situated, near the junction of iris and cornea. Then it flows through, canal of Schlemm and reaches the venous system via, anterior ciliary vein (Fig. 165.7)., , 1. Capsule, Capsule is a highly elastic membrane that covers the, lens., 2. Anterior Epithelium, , Functions of Aqueous Humor, Aqueous humor, i. Maintains the shape of eyeball, ii. Maintains the intraocular pressure, iii. Provides nutrients, oxygen and electrolytes to, avascular structures such as lens and cornea, iv. Removes the metabolic end products from lens and, cornea., , INTRAOCULAR PRESSURE, Intraocular pressure is the measure of fluid pressure, in eye, exerted by aqueous humor. Normal intraocular, pressure varies between 12 and 20 mm Hg., , FIGURE 165.7: Circulation and drainage of aqueous humor
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Chapter 165 t Structure of the Eye 973, 3. Lens Substance, , INNERVATION OF OCULAR MUSCLES, , Lens is formed by long lens fibers derived from anterior, epithelium. Lens fibers are prismatic in nature and are, arranged in concentric layers., , Innervation of Intrinsic Muscles, , CHANGES IN THE LENS DURING OLD AGE, Elastic property of lens is decreased in old age due to, the physical changes in lens and its capsule. It causes, presbyopia (Chapter 171)., In old age, lens becomes opaque and this condition, is called cataract. Refer Applied Physiology in this, chapter for details., , OCULAR MUSCLES, MUSCLES OF THE EYEBALL, Muscles of the eyeball are of two types:, A. Intrinsic muscles, B. Extrinsic muscles., Intrinsic Muscles, Intrinsic muscles are formed by smooth muscle fibers, and are controlled by autonomic nerves., Intrinsic muscles of eye are:, 1. Constrictor papillae, 2. Dilator papillae, 3. Ciliary muscle., Actions of constrictor pupillae and dilator pupillae, are already explained along with iris. Contraction of, ciliary muscle increases the anterior curvature of lens, during accommodation (Chapter 169)., Extrinsic Muscles, In general, the term ‘ocular muscles’ refers to extrinsic, muscles of the eyeball. Extrinsic muscles are formed, by skeletal muscle fibers and are controlled by the, somatic nerves. Eyeball moves within the orbit by six, extrinsic skeletal muscles (Fig. 165.8). One end of, each muscle is attached to the eyeball and the other, end to the wall of orbital cavity. There are four straight, muscles (rectus) and two oblique muscles., Extrinsic muscles are:, 1. Superior rectus, 2. Inferior rectus, 3. Medial or internal rectus, 4. Lateral or external rectus, 5. Superior oblique, 6. Inferior oblique., , Intrinsic muscles of eyeball are innervated by both, sympathetic and parasympathetic divisions of, autonomic nervous system., , Parasympathetic nerve fibers, Parasympathetic, , preganglionic, , fibers, , arise, , from, , Edinger-Westphal nucleus of III cranial nerve. After, , passing through III cranial nerve, these fibers synapse, with postganglionic neurons in ciliary ganglion., Postganglionic fibers arising from here pass through, ciliary nerves and innervate the ciliary muscle and, constrictor pupillae. Stimulation of parasympathetic, nerve fibers causes contraction of ciliary muscle and, constrictor pupillae., Sympathetic nerve fibers, Sympathetic preganglionic nerve fibers arise from, lateral horn of first thoracic segment of spinal cord,, pass through sympathetic chain and synapse with, neurons of superior cervical sympathetic ganglion., Postganglionic fibers arising from this ganglion, run, along with carotid artery and its branches, to reach, the intrinsic muscles of the eyeball. Stimulation of, sympathetic nerve fibers causes relaxation of ciliary, muscle and contraction of dilator pupillae., Innervation of Extrinsic Muscles, Extrinsic muscles of eyeball are innervated by somatic, motor nerve fibers. Somatic nerve fibers arise from, cranial nerve nuclei in brainstem and reach the ocular, muscles via three cranial nerves:, 1. Oculomotor (third) nerve, 2. Trochlear (fourth) nerve, 3. Abducent (sixth) nerve., 1. Oculomotor Nerve, Oculomotor nerve supplies:, i. Superior rectus, ii. Inferior rectus., iii. Medial rectus (internal rectus), iv. Inferior oblique., 2. Trochlear Nerve, Trochlear nerve supplies the superior oblique., 3. Abducent Nerve, Abducent nerve supplies the lateral rectus (external, rectus).
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974 Section 11 t Special Senses, , FIGURE 165.8: Extrinsic muscles of eyeball., Numbers in parenthesis indicate the cranial nerve supplying the muscle., , OCULAR MOVEMENTS, , 1. Elevation or Upward Movement, , Eyeball moves or rotates within the orbital socket in any, of the three primary axes, namely vertical, transverse, and anteroposterior axis (Fig. 165.9 and Table 165.1)., , Elevation of eyeball occurs because of the contraction, of superior rectus and inferior oblique muscles., , MOVEMENTS IN VERTICAL AXIS, Movements of eyeball in vertical axis or in horizontal, plane are of two types:, 1. Abduction or Lateral Movement, or Outward Movement, Abduction of eyeball is due to the contraction of lateral, rectus mainly. It is supported by the two oblique, , 2. Depression or Downward Movement, Depression of eyeball is brought out by inferior rectus, and superior oblique., MOVEMENTS IN ANTEROPOSTERIOR AXIS, Movements of eyeball in anteroposterior axis or in the, frontal plane are called torsion or wheel movements., Torsion movements are two types, namely extorsion, and intorsion., , muscles., , 1. Extorsion, , 2. Adduction or Medial Movement, or Inward Movement, , During extorsion, the eyeball is rotated in such a way, that the cornea turns in upward and outward direction., This movement is due to contraction of inferior oblique, and inferior rectus., , Adduction of the eyeball occurs because of the action, of medial or internal rectus, along with action of, superior rectus and inferior rectus., MOVEMENTS IN TRANSVERSE AXIS, Movements of eyeball in transverse axis or in sagittal, plane are of two types:, , 2. Intorsion, During intorsion, the eyeball is rotated so that, the, cornea moves in downward and inward direction. It is, produced by the contraction of superior oblique and, superior rectus muscles.
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Chapter 165 t Structure of the Eye 975, , FIGURE 165.9: Diagram showing the movements of right eye. MR = Medial rectus, SO = Superior oblique,, LR = Lateral rectus, IO = Inferior oblique, SR = Superior rectus, IR = Inferior rectus., TABLE 165.1: Muscles taking part in ocular movements, Movement, , Primary muscle, , Secondary muscle, , 1. Abduction, , Lateral rectus, , Superior oblique, Inferior oblique, , 2. Adduction, , Medial rectus, , Superior rectus, Inferior rectus, , 3. Elevation, , Superior rectus, , Inferior oblique, , 4. Depression, , Inferior rectus, , Superior oblique, , 5. Extorsion, , Inferior oblique, , Inferior rectus, , 6. Intorsion, , Superior oblique, , Superior rectus, , SIMULTANEOUS MOVEMENTS, OF BOTH EYEBALLS, Simultaneous movements of both eyeballs are of four, types:, , of medial rectus and simultaneous relaxation of, lateral rectus of both eyes. Visual axes move close to, each other. Convergence of eyeballs occurs during, accommodation., Divergence, Divergence is the movement of both eyeballs towards, temporal side. It is due to the simultaneous contraction, of lateral rectus and simultaneous relaxation of medial, rectus of both eyes. Visual axes of the eyes move away, from each other., 3. Pursuit Movement, Pursuit movement is the movement of eyeballs along, with object, when eyeballs follow a moving object., 4. Saccadic Movement, , 1. Conjugate Movement, Conjugate movement is the movement of both eyeballs, in the same direction. Visual axes of both eyes remain, parallel. It is due to contraction of medial rectus of one, eye and lateral rectus of the other eye., , Saccadic movement is the quick jerky movement, of both eyeballs when the fixation of eyes (gaze) is, shifted from one object to another object. It is also, called optokinetic movement., , APPLIED PHYSIOLOGY, 2. Disjugate Movement, Disjugate movement is the movement of both eyeballs, in opposite direction. There are two types of disjugate, movement, namely convergence and divergence., Convergence, Convergence is the movement of both eyeballs, towards nose. It is due to simultaneous contraction, , GLAUCOMA, Glaucoma is a group of diseases characterized by, increased intraocular pressure, which causes damage, of optic nerve, resulting in blindness., In glaucoma, the drainage of aqueous humor, through trabeculae is blocked, resulting in increased, intraocular pressure. When the intraocular pressure
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976 Section 11 t Special Senses, rises above 60 mm Hg, the optic nerve fibers at the optic, disk are compressed. Initially it decreases the visual, field (loss of peripheral vision), which eventually leads, to total blindness., However, with early treatment, often the eyes may, be protected against serious vision loss. Untreated, glaucoma leads to permanent damage of the optic, nerve and results in blindness. In old age, glaucoma, occurs due to the obstruction of trabeculae by fibrous, structures., Types of Glaucoma, Elevation of intraocular pressure causing glaucoma can, occur at any stage of life. Congenital glaucoma develops, in babies born with increased intraocular pressure., Glaucoma in infants is called infantile glaucoma. When it, occurs in childhood, it is known as juvenile glaucoma., Generally glaucoma is divided into two types:, 1. Primary open-angle glaucoma, 2. Primary angle-closure glaucoma., 1. Primary open-angle glaucoma (POAG), POAG is the most common type of glaucoma and it, accounts for about 80% of all cases of glaucoma. The, term open-angle refers to drainage system, which is, responsible for draining the aqueous humor from the, eye. Actually, in POAG there is no visible obstruction, in the drainage system. Still intraocular pressure, increases, causing damage to optic nerve. Exact, cause of POAG is not known yet. It is suggested that, a microscopic (minute) blockage in drainage system, beyond limbus may obstruct the flow of aqueous humor., It causes a gradual increase in intraocular pressure., 2. Primary angle-closure glaucoma (PACG), PACG is characterized by visible obstruction of drainage system for aqueous humor. Iris is pushed against, cornea, preventing the drainage of aqueous humor., Intraocular pressure rises over the period of few hours., Causes of Glaucoma, Major cause of glaucoma is the blockage in drainage, system of aqueous humor in trabeculae, resulting, in increased intraocular pressure. Glaucoma also, develops secondary to other disorders, which affect, the eyes. Common causes of secondary glaucoma are, diabetes, inflammation or injury to eye and excess use, of drugs such as corticosteroid., Symptoms of Glaucoma, Primary open-angle glaucoma is a silent chronic, disease without any early symptoms. Symptoms that, , develop in later stages include heaviness around, eyeball, headache and rapid reduction in visual acuity, and visual field., Early symptoms of angle-closure glaucoma are, severe pain in eye or eyebrow, headache, nausea,, blurred vision and rainbow halo (colored rings) around, bulb light. Immediate care should be taken if two or, more of these symptoms appear together., Treatment for Glaucoma, Treatment does not cure the disease but can prevent, further damage of optic nerve. Treatment is aimed at, lowering the intraocular pressure. It is achieved by, using eye drops or medicines alone or in combination, with laser treatment. If intraocular pressure cannot be, controlled by these methods, surgery is required., CATARACT, Cataract is the opacity or cloudiness in the natural lens, of the eye. It is the major cause of blindness worldwide., When lens becomes cloudy, light rays cannot pass, through it easily and vision is blurred. Cataract develops, in old age after 55 to 60 years., Lens is situated within the sealed capsule. Old cells, die and accumulate within the capsule. Over years, the, accumulation of cells is associated with accumulation of, fluid and denaturation of proteins in lens fibers, causing, cloudiness of lens and blurred image., Causes of Cataract, In addition to age, cataract develops due to many other, causes such as:, 1. Eye injuries, 2. Previous eye surgery, 3. Diseases such as diabetes, Wilson disease and, hypocalcemia, 4. Long-term use of drugs such as steroids,, diuretics and tranquilizers, 5. Long-term unprotected exposure to sunlight, 6. Alcoholism, 7. Family history, 8. Diet containing large quantity of salt., Symptoms of Cataract, Common symptoms of cataract:, 1. Glare, 2. Painless blurred vision, 3. Poor night vision, 4. Diplopia in affected eye, 5. Need for a bright light while reading, 6. Fading of colors.
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Chapter 165 t Structure of the Eye 977, Treatment for Cataract, Surgery is the only treatment for cataract. During surgery,, cloudy lens is removed from the eye through a surgical, incision. The natural lens is replaced with a permanent,, clear and plastic intraocular lens (IOL) implant. Different, procedures are followed to remove the cloudy lens., Common methods are:, 1. Extracapsular extraction, Extracapsular extraction is rather an old technique. A, 12 mm incision is made in the eye under an operating, microscope, to remove the lens as a whole. Posterior, capsule of lens is left in place to hold the IOL implant., Multiple sutures are required to seal the eye after, , surgery. Sutures must be perfect; otherwise astigmatism, may develop., 2. Phacoemulsification, Phacoemulsification (Phaco) is the current technique., Phaco is the procedure in which cataract is broken into, smaller fragments by ultrasonic vibrations. It is done, , through a small (3 mm) incision. An ultrasound (or, laser) probe is used to break the lens material without, damaging the capsule. Lens fragments are aspirated, out of the eye. A foldable IOL is then introduced through, the incision. After entering the eye, the lens unfolds to, take position inside the capsule. No sutures are needed,, as the incision is self-sealing.
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Chapter, , Visual Process, , 166, , INTRODUCTION, IMAGE FORMING MECHANISM, NEURAL BASIS OF VISUAL PROCESS, , , , , STRUCTURE OF ROD CELL, STRUCTURE OF CONE CELL, FUNCTIONS OF RODS AND CONES, , CHEMICAL BASIS OF VISUAL PROCESS, , , , , , , , RHODOPSIN, PHOTOTRANSDUCTION, PHOTOSENSITIVE PIGMENTS IN CONES, DARK ADAPTATION, LIGHT ADAPTATION, NIGHT BLINDNESS, , ELECTRICAL BASIS OF VISUAL PROCESS – ELECTRORETINOGRAM, , , , , DEFINITION, METHOD OF RECORDING ERG, WAVES OF ERG, , ACUITY OF VISION, , , , DEFINITION, TEST FOR VISUAL ACUITY, , INTRODUCTION, , IMAGE FORMING MECHANISM, , Visual process is the series of actions that take place, during visual perception. During visual process, image, of an object seen by the eyes is focused on retina, resulting in production of visual perception of that object., When the image of an object in environment is, focused on retina, the energy in visual spectrum is, converted into electrical potentials (impulses) by rods, and cones of retina through some chemical reactions., Impulses from rods and cones reach the cerebral, cortex through optic nerve and the sensation of vision, is produced in cerebral cortex. Thus, process of visual, sensation is explained on the basis of image formation, and neural, chemical and electrical phenomena., , While looking at an object, light rays from that object are, refracted and brought to a focus upon retina. Image of, the object falls on the retina in an inverted position and, reversed side to side. Inspite of this, the object is seen, in an upright position. It is because of the role played by, cerebral cortex., Light rays are refracted by the lens and cornea., Refractory power is measured in diopter (D). A diopter, is the reciprocal of focal length expressed in meters., Focal length of cornea is 24 mm and refractory, power is 42 D. Focal length of lens is 44 mm and, refractory power is 23 D.
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Chapter 166 t Visual Process 979, , NEURAL BASIS OF VISUAL PROCESS, Retina contains the visual receptors (Fig. 166.1), which, are also called light sensitive receptors, photoreceptors, or electromagnetic receptors. Visual receptors are, , rods and cones. There are about 6 million cones and 12, million rods in the human eye. Distribution of the rods, and cones varies in different areas of retina. Fovea has, only cones and no rods. While proceeding from fovea, towards the periphery of retina, the rods increase and, the cones decrease in number. At the periphery of the, retina, only rods are present and cones are absent., STRUCTURE OF ROD CELL, Rod cells are cylindrical structures with a length of, about 40 to 60 µ and a diameter of about 2 µ., Each rod is composed of four structures:, 1. Outer segment, 2. Inner segment, 3. Cell body, 4. Synaptic terminal., FIGURE 166.1: Structure of visual receptors, , 1. Outer Segment, Outer segment of rod cell is long and slender. So it, gives the rod-like appearance. It is in close contact, with the pigmented epithelial cells. Outer segment of, rod cell is formed by the modified cilia and it contains, a pile of freely floating flat membranous disks. There, are about 1,000 disks in each rod. Disks in rod cells, are closed structures and contain the photosensitive, pigment, the rhodopsin., Rhodopsin is synthesized in inner segments and, inserted into newly formed membranous disks at the, inner portion of outer segment. New disks push the, older disks towards outer tip. Older disks are engulfed, (by phagocytosis) from tip of the outer segment by cells, of pigment epithelial layer. Thus, outer segment of rod, cell is constantly renewed by the formation of new disks., Rate of formation of new disks is 3 or 4 per hour., 2. Inner Segment, Inner segment is connected to outer segment by means, of modified cilium. Inner segment contains many types, of organelles with large number of mitochondria., 3. Cell Body, A slender fiber called rod fiber arises from inner, segment of the rod cell and passes to outer nuclear, layer through external limiting membrane. In outer, nuclear layer, the enlarged portion of this fiber forms the, cell body or rod granule that contains the nucleus., , 4. Synaptic Terminal, A thick fiber arising from the cell body passes to outer, plexiform layer and ends in a small and enlarged, synaptic terminal or body. Synaptic terminal of the rods, synapses with dendrites of bipolar cells and horizontal, cells. Synaptic vesicles present in the synaptic terminal, contain neurotransmitter, glutamate., STRUCTURE OF CONE CELL, Cone cell is the visual receptor with length of 35 µ to, 40 µ and a diameter of about 5 µ. Generally, the cone, cell is flask shaped. Shape and length of the cone, vary in different parts of the retina. Cones in the fovea, are long, narrow and almost similar to rods. Near the, periphery of retina, cones are short and broad., Like rods, cones are also formed by four parts:, 1. Outer segment, 2. Inner segment, 3. Cell body, 4. Synaptic terminal., 1. Outer Segment, Outer segment is small and conical. It does not contain, separate membranous disks as in rods. In cone, the, infoldings of cell membrane form saccules, which are, the counterparts of rod disks.
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980 Section 11 t Special Senses, Photopigment of cone is synthesized in the inner, segment and incorporated into the folding of surface, membrane forming saccule. Renewal of outer segment, of cone is a slow process and it differs from that in rods., It occurs at many sites of the outer segment of cone., 2. Inner Segment, In cones also, the inner segment is connected to outer, segment by a modified cilium as in the case of rods., Though various types of organelles are present in this, segment, the number of mitochondria is more., 3. Cell Body, Cone fiber arising from inner segment is thick and it, enters the inner nuclear layer through external limiting, membrane. In the inner nuclear layer, cone fiber forms, the cell body or cone granule that possesses nucleus., 4. Synaptic Terminal, Fiber from cell body of cone leaves the inner nuclear, layer and enters outer flexiform layer. Here, it ends, in the form of an enlarged synaptic terminal or body., Synaptic vesicle present in the synaptic terminal of cone, cell also possesses the neurotransmitter, glutamate., FUNCTIONS OF RODS AND CONES, Functions of Rods, Rods are very sensitive to light and have a low threshold. So, the rods are responsible for dim light vision or, night vision or scotopic vision. But, rods do not take, part in resolving the details and boundaries of objects, (visual acuity) or the color of the objects (color vision)., Vision by rod is black, white or in the combination of, black and white namely, grey. Therefore, the colored, objects appear faded or greyish in twilight., Functions of Cones, Cones have high threshold for light stimulus. So, the, cones are sensitive only to bright light. Therefore, cone, cells are called receptors of bright light vision or daylight, vision or photopic vision. Cones are also responsible, for acuity of vision and the color vision (Table 166.1)., Achromatic Interval, When an object is placed in front of a person in a, dark room, he cannot see any object. When there is, slight illumination, the person can see the objects but, , without color. It is because, at this level, only rods are, stimulated. When, the illumination is increased, the, threshold for cones is reached. Now, the person can, see the objects in finer details and in color. Interval, between the threshold for rods and cones, i.e. interval, from when an object is first seen and the time when that, object is seen with color is called achromatic interval., , CHEMICAL BASIS OF VISUAL PROCESS, Photosensitive pigments present in rods and cones, are concerned with chemical basis of visual process., Chemical reactions involved in these pigments lead, to the development of electrical activity in retina and, generation of impulses (action potentials), which are, transmitted through optic nerve. Photochemical changes, in the visual receptor cells are called Wald visual cycle., RHODOPSIN, Rhodopsin or visual purple is the photosensitive, pigment of rod cells. It is present in membranous disks, located in outer segment of rod cells., Chemistry of Rhodopsin, Rhodopsin is a conjugated protein with a molecular, weight of 40,000. It is made up of a protein called, opsin and a chromophore. Opsin present in rhodopsin, is known as scotopsin. Chromophore is a chemical, substance that develops color in the cell. Chromophore, present in the rod cells is called retinal. Retinal is the, aldehyde of vitamin A or retinol., Retinal is derived from food sources and it is not, synthesized in the body. It is derived from carotinoid, substances like β-carotene present in carrots., Retinal is present in the form of 11-cis retinal known, as retinine 1. Retinine 1 is present in human eyes. It, is different from retinine 2 that is present in the eyes, of some animals. Significance of 11-cis form of retinal, is that, only in this form it combines with scotopsin to, synthesize rhodopsin., Photochemical Changes in Rhodopsin –, Wald Visual Cycle, When retina is isolated and examined in dark, the rods, appear in red because of rhodopsin. During exposure, to light, rhodopsin is bleached and the color becomes, yellow. When rhodopsin absorbs the light that falls, on retina, it is split into retinine and the protein called, opsin through various intermediate photochemical, reactions (Fig. 166.2).
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Chapter 166 t Visual Process 981, TABLE 166.1: Rods versus cones, Features, , Rods, , Cones, , Number in each eye, , 12 million, , 6 million, , Length, , 40 to 60 µ, , 35 to 40 µ, , Diameter, , 2µ, , 5µ, , Shape, , Cylindrical, , Flask shaped, , Outer segment, , Long and slender, , Small and conical, , Sensitivity to light, , More sensitive, , Sensitive only to bright light, , Threshold, , Low, , High, , Type of vision responsible for, , Dim light vision or night vision or, scotopic vision, , Bright light vision or day light vision or, photopic vision, , Acuity of vision, , Not responsible, , Responsible, , Color vision, , Not responsible, , Responsible, , Photosensitive pigment, , Rhodopsin, , Porphyropsin or iodopsin or cyanopsin, , FIGURE 166.2: Photochemical changes and resynthesis of rhodopsin (Wald visual cycle)., NADH2 = Reduced nicotinamide adenine dinucleotide.
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982 Section 11 t Special Senses, Following changes occur due to absorption of light, energy by rhodopsin:, 1. First, rhodopsin is decomposed into bathorhodopsin, that is very unstable, 2. Bathorhodopsin is converted into lumirhodopsin, 3. Lumirhodopsin decays into metarhodopsin I, 4. Metarhodopsin I is changed to metarhodopsin II, 5. Metarhodopsin II is split into scotopsin and all-trans, retinal, , 6. All-trans retinal is converted into all-trans retinol, (vitamin A) by the enzyme dehydrogenase in the presence of reduced nicotinamide adenine dinucleotide, (NADH2)., Metarhodopsin is usually called activated rhodopsin, since it is responsible for development of receptor, potential in rod cells., Resynthesis of Rhodopsin, First, the all-trans retinal derived from metarhodopsin II, is converted into 11-cis retinal by the enzyme retinal, isomerase. 11-cis retinal immediately combines with, scotopsin to form rhodopsin., All-trans retinol (vitamin A) also plays an important, role in the resynthesis of rhodopsin. All-trans retinol is, converted into 11-cis retinol by the activity of enzyme, retinol isomerase. It is converted into 11-cis retinal,, which combines with scotopsin to form rhodopsin. Alltrans retinol is also reconverted into all-trans retinal., Rhodopsin can be synthesized directly from alltrans retinol (vitamin A) in the presence of nicotinamide, adenine dinucleotide (NADH2). However, the synthesis, of rhodopsin from 11-cis retinal (retinine) is faster than, from 11-cis retinol (vitamin A)., PHOTOTRANSDUCTION, Visual or phototransduction is the process by which, light energy is converted into receptor potential in, , visual receptors., Resting membrane potential in other sensory, receptor cells is usually between –70 and –90 mV., However, in the visual receptors during darkness,, negativity is reduced and resting membrane potential, is about –40 mV. It is because of influx of sodium ions., Normally in dark, sodium ions are pumped out of inner, segments of rod cell to ECF. However, these sodium, ions leak back into the rod cells through membrane of, outer segment and reduce the electronegativity inside, rod cell (Fig. 166.3). Thus, sodium influx maintains, a decreased negative potential up to –40 mV. This, potential is constant and it is also called dark current., , FIGURE 166.3: Maintenance of dark current (resting, potential) in outer segment of rod cell, , Influx of sodium ions into outer segment of rod, cell occurs mainly because of cyclic guanosine, monophosphate (cGMP) present in the cytoplasm of, cell. The cGMP always keeps the sodium channels, opened. Closure of sodium channels occurs due to, reduction in cGMP. Concentration of sodium ions inside, the rod cell is regulated by sodium potassium pump., When light falls on retina, rhodopsin is excited, leading to development of receptor potential in the, rod cells., Phototransduction Cascade, of Receptor Potential, Following is the phototransduction cascade of receptor, potential (Fig. 166.4):, 1. When a photon (the minimum quantum of light, energy) is absorbed by rhodopsin, the 11-cis, retinal is decomposed into metarhodopsin through, few reactions mentioned earlier. Metarhodopsin, II is considered as the active form of rhodopsin., It plays an important role in the development of, receptor potential., 2. Metarhodopsin II activates a G protein called, transducin that is present in rod disks
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Chapter 166 t Visual Process 983, Significance of Hyperpolarization, Hyperpolarization in visual receptor cells reduces the, release of synaptic transmitter glutamate. It leads to, development of response in bipolar cells and ganglionic, cells so that, the action potentials are transmitted to, cerebral cortex via optic pathway., PHOTOSENSITIVE PIGMENTS IN CONES, Photosensitive pigment in cone cells is of three types,, namely porphyropsin, iodopsin and cyanopsin. Only, one of these pigments is present in each cone. Photopigment in cone cell also is a conjugated protein made up of, a protein and chromophore. Protein in cone pigment is, called photopsin, which is different from scotopsin, the, protein part of rhodopsin. However, chromophore of cone, pigment is the retinal that is present in rhodopsin. Each, type of cone pigment is sensitive to a particular light and, the maximum response is shown at a particular light and, wave-length. Details are given in the Table 166.2., Various processes involved in phototransduction, in cone cells are similar to those in rod cells., DARK ADAPTATION, Definition, , FIGURE 166.4: Phototransduction cascade., cGMP = Cyclic guanosine monophosphate., , 3. Activated transducin activates the enzyme called, cyclic guanosine monophosphate phosphodiesterase (cGMP phosphodiesterase), which is also, present in rod disks, 4. Activated cGMP phosphodiesterase hydrolyzes, cGMP to 5’-GMP, 5. Now, the concentration of cGMP is reduced in rod cell, 6. Reduction in concentration of cGMP immediately, causes closure of sodium channels in the membrane, of visual receptors, 7. Sudden closure of sodium channels prevents entry, of sodium ions leading to hyperpolarization. The, potential reaches –70 to –80 mV. It is because of, sodium-potassium pump., Thus, the process of receptor potential in visual, receptors is unique in nature. When other sensory, receptors are excited, the electrical response is in the, form of depolarization (receptor potential). But, in visual, receptors, the response is in the form of hyperpolarization., , Dark adaption is the process by which the person is, able to see the objects in dim light. If a person enters, a dim-lighted room (darkroom) from a bright-lighted, area, he is blind for some time, i.e. he cannot see any, object. After sometime his eyes get adapted and he, starts seeing the objects slowly. Maximum duration for, dark adaptation is about 20 minutes., Causes for Dark Adaptation, Dark adaptation is due to the following changes in, eyeball:, 1. Increased sensitivity of rods as a result, of resynthesis of rhodopsin, Time required for dark adaptation is partly determined, by the time for resynthesis of rhodopsin. In bright light,, most of the pigment molecules are bleached (broken, down). But in dim light, it requires some time for, regeneration of certain amount of rhodopsin, which is, necessary for optimal rod function., Dark adaptation occurs in cones also., 2. Dilatation of pupil, Dilatation of pupil during dark adaptation allows more, and more light to enter the eye.
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984 Section 11 t Special Senses, TABLE 166.2: Sensitivity of cone pigments, Pigment, , Sensitive to, , Wavelength, of maximum response, , Porphyropsin Red, , 665 nm, , Iodopsin, , Green, , 535 nm, , Cyanopsin, , Blue, , 445 nm, , Radiologists, aircraft pilots and others, who need, maximal visual sensitivity in dim light, wear red glass, before entering dim-lighted area, because red light of, spectrum stimulates the rods slightly while the cones, are allowed to function well. Thus, the person wearing, red goggles can see well in bright-lighted area and, also can see the objects clearly, as soon as he enters, the dim-lighted area., Dark Adaptation Curve, Dart adaptation curve is the curve that demonstrates, the relationship between threshold of light stimulus, (illumination) and time spent in dark., Procedure, Experiment to obtain dark adaptation curve is done in, a completely dark room. First, the subject is exposed, to a bright light in order to bleach (breakdown) most of, the photopigment in retina. The subject looks directly, at a bright flashing light with a wavelength of 420 nm, against dark background for about 5 to 7 minutes., Then the bright light is switched off and the subject, is in dark. Now a small dim light (stimulus) is produced., Immediately, the absolute threshold (minimum strength, of stimulus; minimum intensity of light stimulus) for, detecting this dim light is determined by adjusting the, intensity of light (illumination). Time interval between, the switching off bright light and detection of dim, light is noted. After a short time, absolute threshold, is measured again and elapsed time is noted. This, procedure is repeated for about 30 minutes., When the experiment is completed, results are, plotted and the dark adaptation curve is obtained., , Cone adaptation, This first phase is rapid and it is completed in 8 to 10, minutes. During this period the threshold decreases, by 2 to 3 log units. That is the sensitivity of the eye, in dark room increases by 1,000 times within 8 to 10, minutes. By this time, the cones get adapted., Rod-cone break, After the first phase, there is a sudden change in slope, of the curve and this point of curve is called rod-cone, break. Rod-cone break represents the point where, rod sensitivity begins to exceed cone sensitivity and, the remaining part of the curve is determined by the, continuing adaptation of rods., During this phase the threshold decreases further by, 5 to 6 log units. That is the sensitivity of eye in dark room, increases by 100,000 to 1,000,000 times within 20 to 30, minutes. By this time, rods get adapted completely., LIGHT ADAPTATION, Rod adaptation, Second phase of the curve is slow. During this phase,, there is a gradual decrease in the threshold and it is, completed in 20 to 30 minutes., , Parts of dark adaptation curve, Dark adaptation curve is biphasic. First part of the, curve represents threshold of photopic vision, which, indicates the cone adaptation. Second part of the, curve represents threshold of scotopic vision, which, indicates the rod adaptation (Fig. 166.5)., , FIGURE 166.5: Dark adaptation curve. During cone adaptation, threshold decreases by 3 logs and sensitivity of the, eyes increases 1,000 times. During rod adaptation, threshold decreases by 6 logs and sensitivity of the eyes increases, by 1,000,000.
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Chapter 166 t Visual Process 985, Definition, Light adaptation is the process in which eyes get, adapted to increased illumination. When a person enters, a bright-lighted area from a dim-lighted area, he feels, discomfort due to the dazzling effect of bright light. After, some time, when the eyes become adapted to light, he, sees the objects around him without any discomfort. It is, the mere disappearance of dark adaptation. Maximum, period for light adaptation is about 5 minutes., Causes of Light Adaptation, There are two causes of light adaptation:, 1. Reduced sensitivity of rods, During light adaptation, the sensitivity of rods, decreases. It is due to the breakdown of rhodopsin., , a characteristic sequence of potential changes occurs,, which can be recorded in the form of ERG. This, diagnostic procedure is useful in determining retinal, disorders such as cone dystrophy (degeneration of, cones) and retinitis pigmentosa (hyperactivity of the, pigmented retinal epithelial cells, leading to damage of, photoreceptors and blindness)., METHOD OF RECORDING ERG, Electroretinogram is recorded by using a galvanometer, or a suitable recording device. Recording electrode is, placed on the cornea of eye in its usual forward up, looking position. Indifferent electrode is placed over, any moist surface of body, like inside the mouth., WAVES OF ELECTRORETINOGRAM, , NIGHT BLINDNESS, , Electroretinogram has 4 waves namely ‘A’, ‘B’, ‘C’ and, ‘D’ (Fig. 166.6). ‘A’ is the only negative wave and other, three are positive waves. ‘A’, ‘B’ and ‘C’ waves occur, when light stimulus falls on retina. ‘D’ wave occurs when, light stimulus is stopped. ‘A’ and ‘B’ waves arise from, rods and cones. ‘C’ wave arises from pigment epithelial, layer and ‘D’ wave arises from inner nuclear layer., , Definition, , ACUITY OF VISION, , 2. Constriction of pupil, Constriction of pupil reduces the quantity of light rays, entering the eye., , Night blindness is defined as the loss of vision when light, in the environment becomes dim. It is otherwise called, nyctalopia or defective dim light (scotopic) vision., Causes of Night Blindness, , DEFINITION, Acuity of vision is the ability of eye to determine the, precise shape and details of the object. It is also called, visual acuity. Acuity of vision is also defined as the ability, , Night blindness is due to the deficiency of vitamin A,, which is essential for the function of rods., Deficiency of vitamin A occurs because of following, causes:, 1. Diet containing less amount of vitamin A, 2. Decreased absorption of vitamin A from intestine., Vitamin A deficiency causes defective cone, function. Prolonged deficiency leads to anatomical, changes in rods and cones and finally the degeneration, of other retinal layers occurs. So, retinal function can, be restored, only if treatment is given with vitamin A, before the visual receptors start degenerating., , ELECTRICAL BASIS OF VISUAL, PROCESS – ELECTRORETINOGRAM, DEFINITION, Electroretinogram (ERG) is the record of electrical, activity in retina. When light rays stimulate the retina,, , FIGURE 166.6: Electroretinogram
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986 Section 11 t Special Senses, to recognize the separateness of two objects placed, together. Cones of retina are responsible for acuity, of vision. Visual acuity is highly exhibited in fovea, centralis, which contains only cones. It is greatly, reduced during the refractory errors., TEST FOR VISUAL ACUITY, Acuity of vision is tested for distant vision as well, as near vision. If there is any difficulty in seeing the, distant object or the near object, the defect is known, , as error of refraction. Refractive errors are described, separately in Chapter 171., Distant Vision, Snellen chart is used to test the acuity of vision for dis-, , tant vision in the diagnosis of refractive errors of the eye., Near Vision, Jaeger chart is used to test the visual acuity for near, , vision.
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Chapter, , Field of Vision, , 167, , DEFINITION, BINOCULAR AND MONOCULAR VISION, , , , BINOCULAR VISION, MONOCULAR VISION, , DIVISIONS OF VISUAL FIELD, , , , TEMPORAL AND NASAL FIELDS, UPPER AND LOWER FIELDS, , CORRESPONDING RETINAL POINTS, , , DIPLOPIA, , BLIND SPOT, VISUAL FIELD AND RETINA, MAPPING OF VISUAL FIELD, , DEFINITION, , DIVISIONS OF VISUAL FIELD, , Part of the external world seen by one eye, when it is, fixed in one direction is called field of vision or visual, field of that eye. According to Traquair, the visual field, is described as ‘island of vision, surrounded by a sea, of blindness’., , Visual field of the human eye has an angle of 160°, in horizontal meridian and 135° in vertical meridian., Visual filed is divided into four parts:, 1. Temporal field, 2. Nasal field, 3. Upper field, 4. Lower field., , BINOCULAR AND MONOCULAR VISION, BINOCULAR VISION, , TEMPORAL AND NASAL FIELDS, , Binocular vision is the vision in which both the eyes, are used together, so that a portion of external world is, seen by the eyes together. In human and some animals,, eyeballs are placed in front of the head. So, the visual, fields of both the eyes overlap. Because of this, a portion, of the external world is seen by both the eyes., , Visual field of each eye is divided into two unequal, parts, namely outer or temporal field and the inner, or nasal field, by a vertical line passing through the, fixation point (Fig. 167.1). The fixation point is the, meeting point of visual axis with the object., Temporal part of visual field extends up to about, 100° but the nasal part extends only up to 60°, because, it is restricted by nose., , MONOCULAR VISION, Monocular vision is the vision in which each eye is, used separately. In some animals like dog, rabbit and, horse, the eyeballs are present at the sides of head., So, the visual fields of both eyes overlap to a very, small extent. Because of this, different portion of the, external world is seen by each eye., , UPPER AND LOWER FIELDS, Visual field of each eye is also divided into an upper, field and a lower field by a horizontal line passing, through the fixation point. Extent of the upper field, is about 60°, as it is restricted by upper eyelid and, orbital margin. Extent of lower field is about 75°. It is
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988 Section 11 t Special Senses, , FIGURE 167.1: Divisions of visual field, , restricted by cheek. Thus, the visual field is restricted, in all the sides, except in the temporal part., , CORRESPONDING RETINAL POINTS, Corresponding retinal points are the area in retina, of both eyes, on which the light rays from the object, falls. It occurs in the binocular vision. The two images, developed on retina of both eyes are fused into a single, sensation. So, we see the objects with single image., The single sensation is because of the ocular, muscles, which direct the axes of the eyes in such, a way that the light rays from the object fall upon, the corresponding points of both retinas. If the light, rays do not fall on the corresponding retinal points,, diplopia occurs., DIPLOPIA, Diplopia means double vision. While looking at an, object, if the eyeballs are directed in such a way that, the light rays from the object do not fall upon the, corresponding point on the retina of both eyes, a double, vision occurs, i.e. one single object is seen as two., Causes of Diplopia, 1. Permanent diplopia occurs during paralysis or, weakness of ocular muscles. It occurs in myasthenia, gravis also., 2. In alcoholic intoxication, the imbalanced actions of, ocular muscles produce temporary diplopia, 3. Lesions in III, IV and VI cranial nerves, oculomotor, nucleus, red nucleus and cerebral peduncles also, results in diplopia., Experimental Diplopia, Diplopia can be produced experimentally, by the, following methods:, 1. Applying pressure from outer side of one eye and, thus displacing the eye from its normal position, , 2. By holding an object like pen or pencil vertically, in front of face, at about 5 cm from the root of, nose. It is not possible for the convergence of the, eyeballs sufficiently. The light rays from the object, do not fall on the corresponding retinal points and, diplopia occurs., , BLIND SPOT, Blind spot is the small area of retina where visual, receptors are absent. The optic disk in the retina, does not have any visual receptors and if the image, of any object falls on the optic disk, the object cannot, be seen. So this part of the retina is blind hence the, name blind spot., Normally, the darkness in the visual field due to, the blind spot does not cause any inconvenience, because, the fixation of each eye is at different angles., Even when one eye is closed or blind, the person is, not aware of blind spot. However, one can recognize, blind spot by some experimental procedures., , VISUAL FIELD AND RETINA, Light rays from different halves of each visual field do, not fall on the same halves of the retina. Light rays, from temporal part of visual field of an eye fall on the, nasal half of retina of that eye. Similarly, the light rays, from nasal part of visual field fall on the temporal half, of retina of the same side., , MAPPING OF VISUAL FIELD, The shape and extent of visual field is mapped out by, means of an instrument called Goldmann perimeter, and this technique is called perimetry. Visual field is, also determined by Bjerrum (Tangent) screen or by, confrontation test. Humphrey field analyzer is also, used to map visual field and it is more useful to test, the central portion of visual fields.
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Chapter, , Visual Pathway, , , , , , , , 168, , INTRODUCTION, VISUAL RECEPTORS, FIRST ORDER NEURONS, SECOND ORDER NEURONS, THIRD ORDER NEURONS, CONNECTIONS OF VISUAL RECEPTORS TO OPTIC NERVE, , , , PRIVATE PATHWAY, DIFFUSE PATHWAY, , COURSE OF VISUAL PATHWAY, , , , , , , , OPTIC NERVE, OPTIC CHIASMA, OPTIC TRACT, LATERAL GENICULATE BODY, OPTIC RADIATION, VISUAL CORTEX, , APPLIED PHYSIOLOGY – EFFECTS OF LESION AT DIFFERENT, LEVELS OF VISUAL PATHWAY, , INTRODUCTION, , FIRST ORDER NEURONS, , Visual pathway or optic pathway is the nervous pathway, that transmits impulses from retina visual center in, cerebral cortex., In binocular vision, the light rays from temporal, (outer) half of visual field fall upon the nasal part of, corresponding retina. The rays from nasal (inner) half of, visual field fall upon the temporal part of retina., , First order neurons (primary neurons) are bipolar cells, in the retina. Axons from the bipolar cells synapse with, dendrites of ganglionic cells., , VISUAL RECEPTORS, Rods and cones which are present in the retina of, eye form the visual receptors. Fibers from the visual, receptors synapse with dendrites of bipolar cells of, inner nuclear layer of the retina., , SECOND ORDER NEURONS, Second order neurons (secondary neurons) are the, ganglionic cells in ganglionic cell layer of retina. Axons, of the ganglionic cells form optic nerve. Optic nerve, leaves the eye and terminates in lateral geniculate body., , THIRD ORDER NEURONS, Third order neurons are in the lateral geniculate body., Fibers arising from here, reach the visual cortex.
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990 Section 11 t Special Senses, , CONNECTIONS OF VISUAL, RECEPTORS TO OPTIC NERVE, , COURSE OF VISUAL PATHWAY, , Two pathways exist between the visual receptors and, optic nerve:, 1. Private pathway, 2. Diffuse pathway., PRIVATE PATHWAY, The individual cones in fovea centralis are connected to, separate bipolar cells. Each bipolar cell is connected to, separate ganglionic cell, namely midget ganglionic cell., Thus, individual cone is connected to an individual optic, nerve fiber. This type of private pathway is responsible, for visual acuity and intensity discrimination., DIFFUSE PATHWAY, A number of cones and rods are connected with a, polysynaptic bipolar cell. The bipolar cells are connected, to diffused ganglionic cells. So, there is great overlapping. This type of pathway is present outside the fovea., , Visual pathway consists of six components:, 1. Optic nerve, 2. Optic chiasma, 3. Optic tract, 4. Lateral geniculate body, 5. Optic radiation, 6. Visual cortex., OPTIC NERVE, Optic nerve is formed by the axons of ganglionic cells, (Fig. 168.1). Optic nerve leaves the eye through optic, disk. The fibers from temporal part of retina are in lateral, part of the nerve and carry the impulses from nasal half, of visual field of same eye. The fibers from nasal part, of retina are in medial part of the nerve and carry the, impulses from temporal half of visual field of same eye., OPTIC CHIASMA, Medial fibers of each optic nerve cross the midline and, join the uncrossed lateral fibers of opposite side, to form, , FIGURE 168.1: Visual pathway
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Chapter 168 t Visual Pathway 991, the optic tract (Fig. 168.1). This area of crossing of the, optic nerve fibers is called optic chiasma., , also called geniculocalcarine fibers. Optic radiation, ends in visual cortex (Fig. 168.2)., , OPTIC TRACT, , VISUAL CORTEX, , Optic tract is formed by uncrossed fibers of optic nerve, on the same side and crossed fibers of optic nerve, from the opposite side. All the fibers of optic tract run, backward, outward and towards the cerebral peduncle., While reaching the peduncle, the fibers pass between, tuber cinereum and anterior perforated substance., Then, the fibers turn around the peduncle to reach, the lateral geniculate body in thalamus. Here, many, fibers synapse while few fibers just pass through this, and run towards superior colliculus in midbrain. Fibers, from fovea do not enter superior colliculus., Some fibers from fovea of each side pass through, the optic tract of same side and others through the, optic tract of opposite side. Due to crossing of medial, fibers in optic chiasma, the left optic tract carries, impulses from temporal part of left retina and nasal, part of right retina, i.e. it is responsible for vision in, nasal half of left visual field and temporal half of right, visual field. The right optic tract contains fibers from, nasal half of left retina and temporal half of right retina., It is responsible for vision in temporal half of left visual, field and nasal half of right visual field., , Primary cortical center for vision is called visual cortex,, which is located on the medial surface of occipital lobe., It forms the walls and lips of calcarine fissure in medial, surface of occipital lobe., There is a definite localization of retinal projections, upon visual cortex. In fact, the point to point projection, of retina upon visual cortex is well established. The, peripheral retinal representation occupies the anterior, part of visual cortex. Macular representation occupies, the posterior part of visual cortex near occipital pole., , LATERAL GENICULATE BODY, Majority of the fibers of optic tract terminate in lateral, geniculate body, which forms the subcortical center, for visual sensation. From here, the geniculocalcarine, tract or optic radiation arises. This tract is the last, relay of visual pathway., Some of the fibers from optic tract do not synapse, in lateral geniculate body, but pass through it and, terminate in one of the following centers:, i. Superior colliculus: It is concerned with reflex, movements of eyeballs and head, in response, to optic stimulus, ii. Pretectal nucleus: It is concerned with light, reflexes, iii. Supraoptic nucleus of hypothalamus: It is, concerned with the retinal control of pituitary, in animals. But in human, it does not play any, important role., , Areas of Visual Cortex and their Function, Three areas are present in visual cortex:, i. Primary visual area (area 17), which is concerned, with the perception of visual impulses, ii. Secondary visual area or visual association area, (area 18), which is concerned with the interpretation, of visual impulses, iii. Occipital eye field (area 19), which is concerned, with the movement of eyes (Chapter 152)., , APPLIED PHYSIOLOGY – EFFECTS, OF LESION AT DIFFERENT LEVELS, OF VISUAL PATHWAY, Injury to any part of optic pathway causes visual defect, and the nature of defect depends upon the location, and extent of injury. Loss of vision in one visual field, is known as anopia. Loss of vision in one half of visual, field is called hemianopia (Figs. 168.3 to 168.5)., , OPTIC RADIATION, Fibers from lateral geniculate body pass through, internal capsule and form optic radiation. The fibers, between lateral geniculate body and visual cortex are, , FIGURE 168.2: Representation of visual pathway
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992 Section 11 t Special Senses, Effects of Lesion of Optic Chiasma, Nature of defect depends upon the fibers involved:, i. Pressure on uncrossed lateral fibers by, aneurysmal dilatation of carotid artery causes, blindness in the temporal part of retina of, same side, i.e. the retina cannot receive light, stimulus from the objects in nasal half of same, visual field. So, the hemianopia developed is, called left or right nasal hemianopia., ii. If lateral fibers of both sides are affected, the, vision is lost in nasal half of both visual fields,, causing binasal hemianopia. It occurs due to, dilated third ventricle, which forces the angle of, chiasma against carotid arteries. It also occurs, due to dilatation of carotid artery on both sides., iii. Compression of nasal fibers, i.e. crossed fibers by, pituitary tumor causes bitemporal hemianopia., Effects of Lesion of Optic Tract, Lateral, Geniculate Body and Optic Radiation, , FIGURE 168.3: Types of hemianopia, , Hemianopia is classified into two types:, 1. Homonymous hemianopia, 2. Heteronymous hemianopia., 1. Homonymous hemianopia, Homonymous hemianopia means loss of vision in the, same halves of both the visual fields. Loss of vision in, right half of visual field of both eyes is known as right, homonymous hemianopia. Similarly, left homonymous, hemianopia means loss of vision in left half of visual, field of both eyes., 2. Heteronymous hemianopia, Heteronymous hemianopia means loss of vision in, opposite halves of visual field. For example, binasal, heteronymous hemianopia means loss of vision in, right half of left visual field and left half of right visual, field (nasal half of both visual fields). Bitemporal, heteronymous hemianopia is the loss of sight in left, side of left visual field and right side of right visual field, (temporal half of both visual fields)., Effects of Lesion of Optic Nerve, Lesion in one optic nerve will cause total blindness or, anopia in the corresponding visual field. Lesion occurs, due to increased intracranial pressure., , Lesion of optic tract or lateral geniculate body or optic, radiation causes homonymous hemianopia. In the, right-sided lesion, there is loss of vision in right side of, both retina, i.e. in left side of both visual fields – left, homonymous hemianopia. In the left-sided lesion,, there is loss of vision in left half of retina of both eyes, and loss of sight on right half of both visual fields – right, homonymous hemianopia., Effects of Lesion of Visual Cortex, Lesion of upper or lower part of visual cortex leads to, inferior or superior homonymous hemianopia., Macular sparing, In all the conditions mentioned above, total blindness, does not occur because, the macular vision is not, lost. This phenomenon in which the macular vision is, retained (unaffected) in conditions of hemianopia is, called macular sparing., Macular sparing occurs because of the following, reasons:, i. Fibers from macula project into the visual cortex, of both sides, ii. Fibers from macular region are projected into, both anterior and posterior parts of each visual, cortex., Only the bilateral lesion of visual cortex causes total, blindness.
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Chapter 168 t Visual Pathway 993, , FIGURE 168.4: Effects of lesions of optic pathway. Dark shade in circles indicates blindness., A. Lesion of left optic nerve: Total blindness of left eye, B. Lesion of right optic nerve: Total blindness of right eye, C. Lesion of lateral fibers in left side of optic chiasma: Left nasal hemianopia, D. Lesion of lateral fibers in right side of optic chiasma: Right nasal hemianopia, C + D. Lesion of lateral fibers in both sides of optic chiasma: Binasal hemianopia, E. Lesion of medial fibers in optic chiasma: Bitemporal hemianopia, F. Lesion of left optic radiation: Right homonymous hemianopia, G. Lesion of right optic radiation: Left homonymous hemianopia., , FIGURE 168.5: Visual defects
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Chapter, , Pupillary Reflexes, , 169, , INTRODUCTION, LIGHT REFLEX, , , , , , DIRECT LIGHT REFLEX, INDIRECT LIGHT REFLEX, PATHWAY FOR LIGHT REFLEX, CILIOSPINAL REFLEX, , ACCOMMODATION, , , , , , , DEFINITION, MECHANISM OF ACCOMMODATION, ACCOMMODATION REFLEX, PATHWAY FOR ACCOMMODATION REFLEX, RANGE AND AMPLITUDE OF ACCOMMODATION, , APPLIED PHYSIOLOGY, , , , , ARGYLL ROBERTSON PUPIL, HORNER SYNDROME, PRESBYOPIA, , INTRODUCTION, Pupillary reflexes are the visceral reflexes, which alter, the size of pupil. Pupillary reflexes are classified into, three types:, 1. Light reflex, 2. Ciliospinal reflex, 3. Accommodation reflex., , LIGHT REFLEX, Light reflex is the reflex in which pupil constricts when, light is flashed into the eyes. It is also called pupillary, light reflex. Light reflex is of two types:, 1. Direct light reflex, 2. Indirect light reflex., DIRECT LIGHT REFLEX, Direct light reflex is the reflex in which there is, constriction of pupil in an eye when light is thrown into, , that eye. It is also called the direct pupillary light reflex, or the direct reaction to light., INDIRECT LIGHT REFLEX, Indirect light reflex is the reflex that involves constriction, of pupil in both eyes when light is thrown into one eye., If light is flashed into one eye, the constriction of pupil, occurs in the opposite eye, even though no light rays, falls on that eye. It is otherwise called consensual light, reflex., , PATHWAY FOR LIGHT REFLEX, Pathway for light reflex is slightly deviated from visual, pathway. Fibers of light reflex pathway and the fibers of, visual pathway are the same up to optic tract. Beyond, that, these two sets of fibers are separated., When light falls on the eye, the visual receptors, are stimulated. Afferent (sensory) impulses from the, receptors pass through the optic nerve, optic chiasma, and optic tract. At the midbrain level, few fibers get
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Chapter 169 t Pupillary Reflexes 995, separated from optic tract and synapse on the neurons, of pretectal nucleus, which lies close to the superior, colliculus. Pretectal nucleus of midbrain forms the center, for light reflexes. Efferent (motor) impulses from this, nucleus are carried by short fibers to Edinger-Westphal, nucleus (parasympathetic nucleus) of oculomotor nerve, (third cranial nerve). From Edinger-Westphal nucleus,, preganglionic fibers pass through oculomotor nerve and, reach the ciliary ganglion. Postganglionic fibers arising, from ciliary ganglion pass through short ciliary nerves, and reach the eyeball. These fibers cause contraction of, constrictor pupillae muscle of iris (Fig. 169.1)., Reason for consensual light reflex is that, some, of the fibers from pretectal nucleus of one side cross, to the opposite side and end on opposite EdingerWestphal nucleus., CILIOSPINAL REFLEX, Ciliospinal reflex is the dilatation of pupil in eyes caused, by painful stimulation of skin over the neck. It is due to the, , contraction of dilator pupillae muscle. Sensory impulses, pass through cutaneous afferent nerve. The center is, in first thoracic spinal segment. Efferent impulses pass, through sympathetic fibers and reach dilator pupillae., , ACCOMMODATION, DEFINITION, Accommodation is the adjustment of eye to see either, near or distant objects clearly. It is the process by, which light rays from near objects or distant objects, are brought to a focus on sensitive part of retina. It is, achieved by various adjustments made in the eyeball., MECHANISM OF ACCOMMODATION, Light rays from distant objects are approximately parallel, and are less refracted while getting focused on retina., But, the light rays from near objects are divergent. So,, to be focused on retina, these light rays should be, refracted (converged) to a greater extent. There are, three possible ways by which, accommodation occurs:, 1. Retina must be moved towards or away from the, lens. It is done by shortening or elongation of eyeball., So, the divergent, parallel or convergent rays are, focused accurately. This mechanism is present only, in some molluscs and not in human beings., 2. Lens must be moved towards or away from the, retina. It is done in photography. This mechanism, exists in some fishes., 3. Convexity of lens must be altered, so that the, refractory power of lens is altered according to the, need. This mechanism is present in human eye and, it was first suggested by Young and later supported, by Helmholtz (Fig. 169.2)., Young-Helmholtz Theory, , FIGURE 169.1: Pathway for light reflex, , Young-Helmholtz theory describes how the curvature, of lens increases and thereby, the refractive power of, lens is enhanced. When the eyes are fixed on a distant, object (distant vision) lens is flat due to the traction of, suspensory ligaments, which extend from the capsule, of lens and are attached to ciliary processes. Ciliary, processes are attached to choroid through the ciliary, muscle (Refer Fig. 169.1)., When vision is shifted from the distant object to a, near object (near vision), ciliary muscle contracts and, draws the choroid forward. Ciliary processes are brought, closer to lens, i.e. these processes form a small circle., Suspensory ligaments are slackened. Now, the tension, on lens is released. Lens, due to its elastic property,, bulges forward. Anterior curvature (convexity) of lens
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996 Section 11 t Special Senses, is evident by the change in the size and the position of, second image., Other Adjustments in Eyeball, during Accommodation, In addition to increase in anterior curvature of the lens,, two more adjustments are made in the eyeball during, accommodation for near vision., 1. Convergence of both eyeballs: It is necessary to, bring the retinal images on to the corresponding, points, 2. Constriction of pupil: It is necessary to:, i. Increase the visual acuity by reducing lateral, chromatic and spherical aberrations, ii. Reduce the quantity of light entering eye, iii. Increase the depth of focus through more central, part of lens as its convexity is increased., FIGURE 169.2: Accommodation, , increases greatly. A very little change occurs in posterior curvature. This can be demonstrated by using, Purkinje-Sanson images., In resting eye, the intraocular pressure sets up, tension in choroids and pulls the ciliary processes, backward and outward. Suspensory ligaments are, tensed up and the lens becomes flat., Purkinje-Sanson Images, Purkinje-Sanson images are used to demonstrate the, change in convexity of lens during accommodation for, near vision. A subject is made to sit in a darkroom. A, lighted candle is held in front. One eye is opened and, the other eye is closed. Three images of the flame are, seen in the opened eye (Fig. 169.3)., First image is upright and bright. It shines from, the surface of cornea, which acts as a mirror. Second, image is upright, but dim. It is reflected from the, anterior convex surface of the lens. Third image is, inverted and small. It is formed by posterior surface of, the lens, which acts as a concave mirror., When the person looks at a distant object, the, second image reflected from anterior surface of lens, is near the third image from posterior surface. During, accommodation for near vision, no change occurs either, in first image or the third image. But, the second image, becomes smaller and moves towards the first image., Thus, the increased convexity of the anterior, surface of lens during accommodation for near vision, , FIGURE 169.3: Purkinje-Sanson images
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Chapter 169 t Pupillary Reflexes 997, ACCOMMODATION REFLEX, Accommodation is a reflex action. When a person, looks at a near object after seeing a far object, three, adjustments are made in the eyeballs:, 1. Convergence of the eyeballs due to contraction of, the medial recti, 2. Constriction of the pupil due to the contraction of, constrictor pupillae of iris, 3. Increase in the anterior curvature of the lens due to, contraction of the ciliary muscle., Thus, the accommodation reflex involves both, skeletal muscle (medial recti) and smooth muscle, (ciliary muscle and sphincter pupillae)., During accommodation, all the adjustments are, carried out simultaneously. Although accommodation, , is a reflex action, it can be controlled by willpower to, a certain extent., PATHWAY FOR ACCOMMODATION REFLEX, Afferent Pathway, Visual impulses from retina pass through the optic, nerve, optic chiasma, optic tract, lateral geniculate, body and optic radiation to visual cortex (area 17) of, occipital lobe. From here, the association fibers carry, the impulses to frontal lobe (Fig. 169.4)., Center, The center for accommodation lies in frontal eye field, (area 8) that is situated in the frontal lobe of cerebral, cortex., , FIGURE 169.4: Pathway for accommodation reflex
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998 Section 11 t Special Senses, Efferent Pathway, 1. Efferent fibers to ciliary muscle, and sphincter pupillae, From area 8, the corticonuclear fibers pass via, internal capsule to the Edinger-Westphal nucleus of, third cranial nerve. From here, the preganglionic fibers, pass through the third cranial nerve to ciliary ganglion., Postganglionic fibers from ciliary ganglion pass via the, short ciliary nerves and supply the ciliary muscle and, the constrictor pupillae., 2. Efferent fibers to medial rectus, Some of the fibers from frontal eye field terminate in, the somatic motor nucleus of oculomotor nerve. The, fibers from motor nucleus supply medial rectus., RANGE AND AMPLITUDE, OF ACCOMMODATION, , accommodation., , Since, the focal length of eye is different in near, vision and far vision, the refractive power of eye is also, altered. The refractive power during far vision is called, static refraction (R) and that during near vision is called, dynamic refraction (P). The difference between these, two refractive powers (P – R) is called amplitude of, accommodation, which is expressed in diopter., The refractive power is reciprocal of focal length, and the unit for focal length is 1 meter or 100 cm. The, refractory power is expressed as diopter (D)., For example, in a normal eye, if the near point is 10, cm, the dynamic refraction is:, 1 meter, 10 cm, , =, , 100 cm, 10 cm, , Amplitude of Accommodation at Different Ages, Amplitude of accommodation varies with age., Amplitude of accommodation at different age groups is:, 10 years = 11.0 D, 20 years = 9.5 D, 30 years = 7.5 D, 40 years = 5.5 D, 50 years = 2.0 D, 60 years = 1.2 D, 70 years = 1.0 D, , APPLIED PHYSIOLOGY, , The farthest point from the eye at which the object can, be seen is called far point or punctum remotum. In, the normal eye, it is infinite, i.e. at a distance beyond, 6 meters or 20 feet. It is limited only by the size of, object, clearness of the atmosphere and the curvature, of earth., The nearest point from eye at which the object is, seen clearly is called near point or punctum proximum., It is about 7 to 40 cm, depending upon the age. Distance, between far point and near point is called range of, , P =, , In emmetropic (normal) eye, since the far point is at, infinite distance, the static refraction is taken as zero., Now,, Amplitude of accommodation = P – R, = 10 – 0, = 10 D, , = 10 D, , ARGYLL ROBERTSON PUPIL, Argyll Robertson pupil is a clinical condition in which, the light reflex is lost but the accommodation reflex is, present. It is common in tertiary syphilis. It also occurs, because of lesion in Edinger-Westphal nucleus,, diabetes and alcoholic neuropathy., HORNER SYNDROME, Horner syndrome is an eye disorder caused by damage, to cervical sympathetic nerve. It is also called BernardHorner syndrome, Claude Bernard-Horner syndrome or, oculosympathetic palsy., , Symptoms of Horner syndrome appear on the, affected side. The symptoms are:, 1. Ptosis (drooping of upper eyelid), 2. Swelling of lower eyelid, 3. Miosis (abnormal constriction of pupil), 4. Enophthalmos (sinking of eyeball into its cavity), 5. Absence of sweating on affected side of the face., PRESBYOPIA, In old age, the amplitude of accommodation is decreased and the near point is away from the eye. This, condition is called presbyopia. Details are given in, Chapter 171.
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Chapter, , Color Vision, , 170, , INTRODUCTION, VISIBLE SPECTRUM, , , , , , SPECTRAL COLORS, EXTRASPECTRAL COLORS, PRIMARY COLORS, COMPLEMENTARY COLORS, , THEORIES OF COLOR VISION, , , , , , , THOMAS YOUNG TRICHROMATIC THEORY, HELMHOLTZ TRICHROMATIC THEORY, GRANIT DOMINATOR-MODULATOR THEORY, HARTRIDGE POLYCHROMATIC THEORY, HERING’S THEORY OF OPPOSITE COLORS, , COLOR SENSITIVE AREAS IN RETINA, CONTRAST EFFECTS, , , , SIMULTANEOUS CONTRAST, SUCCESSIVE CONTRAST, , AFTERIMAGE, , , , POSITIVE AFTERIMAGE, NEGATIVE AFTERIMAGE, , APPLIED PHYSIOLOGY – COLOR BLINDNESS, , , , , CAUSES FOR ACQUIRED COLOR BLINDNESS, CLASSIFICATION OF COLOR BLINDNESS, TESTS FOR COLOR BLINDNESS, , INTRODUCTION, Human eye can recognize about 150 different colors in, the visible spectrum. Discrimination and appreciation of, colors depend upon the ability of receptors in retina., , VISIBLE SPECTRUM, SPECTRAL COLORS, When sunlight or white light is passed through a glass, prism, it is separated into different colors. Series, of colored light produced by the prism is called the, visible spectrum. Colors that form the spectrum are, , called spectral colors. Spectral colors are red, orange,, yellow, green, blue, indigo and violet (ROYGBIV or, VIBGYOR). In the spectrum, colors occupy the position, according to their wavelengths. Wavelength is the, distance between two identical points in the wave of, light energy. Accordingly, red has got the maximum, wavelength of about 8,000 Å and the violet has got the, minimum wavelength of about 3,000 Å., Light rays longer than red are called infrared rays., Rays shorter than violet are called ultraviolet rays. But,, these two extraordinary types of rays do not evoke the, sensation of vision. Refraction of spectral colors by the
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1000 Section 11 t Special Senses, prism also depends on wavelengths. Red is refracted, less and violet is refracted more. So, longer the light, rays, lesser is the refraction by the prism., Purkinje Phenomenon, Purkinje phenomenon is the shift of brightest part of, spectrum, when the intensity of illumination is changed., When white light is passed through a prism, it splits, into spectral colors from red to violet and if the colors, are viewed at high illumination, the brightest part of, the spectrum is the yellow, i.e. the brightest part of the, spectrum is shifted to left. But when the light intensity, is reduced to that of twilight, the color of the spectrum, fades. Now the brightest part of spectrum is green, i.e., the brightest part of spectrum is shifted to right. It is, called Purkinje shift or effect., According to Purkinje, this effect is due to the, maximal stimulation of cones by yellow and the, maximal stimulation of rods by green., EXTRASPECTRAL COLORS, Extraspectral colors are the colors other than those, present in visible spectrum. These colors are formed, by the combination of two or more spectral colors. For, example, purple is the combination of violet and red., Pink is the combination of red and white., PRIMARY COLORS, Primary colors are those, which when combined together, produce the white. Primary colors are red, green and, blue. These three colors in equal proportion give white., COMPLEMENTARY COLORS, Complementary colors are the pair of two colors,, which produce white when mixed or combined in, proper proportion. Examples of complementary colors, are red and greenish blue; orange and cyan blue;, yellow and indigo blue; violet and greenish yellow;, purple and green., , THEORIES OF COLOR VISION, Many theories are available to explain the mechanism, of perception of color by eyes. However, most of the, theories are not accepted universally. Following are, the five theories, which are recognized:, 1. THOMAS YOUNG TRICHROMATIC THEORY, According to Thomas Young, retina has three types, of cones. Each one possesses its own photosensitive, , substance. Each cone gives response to one of the, primary colors – red, green and blue. Different color, sensations are produced by the stimulation of various, combinations of these three types of cones. For, sensation of white light, all the three types of cones, are stimulated equally., 2. HELMHOLTZ TRICHROMATIC THEORY, Helmholtz substituted the sensitive filaments of optic, nerve for cones. The sensitive filaments of nerves give, response selectively to one or other of the three primary, colors. It is also called Young-Helmholtz theory., 3. GRANIT DOMINATORMODULATOR THEORY, Granit observed that the ganglionic cells of retina are, stimulated by the whole of the visual spectrum. He, studied the action potentials in ganglionic cells, which, are stimulated by light and obtained some sensitivity, curves. Sensitivity curves were recorded by using, different wavelengths of light both in light-adapted and, dark-adapted eyes. On the basis of these sensitivity, curves, Granit classified the ganglionic cells into two, groups namely, dominators and modulators., Dominators, Dominators are responsible for brightness of light., Dominators are further divided into two types:, i. Dominators for cones, which respond in lightadapted eye and a broad sensitivity curve is, produced with the maximum response around, the wavelengths 55 Å, ii. Dominators for rods, which respond in darkadapted eye and in the sensitivity curve the, maximum response is given at the wavelengths, of 500 Å., Modulators, Modulators are responsible for different color sensations. Modulators are of three types:, i. Modulators of blue, which are stimulated by light, with wavelengths of 450 to 470 Å, ii. Modulators of green, which are stimulated by, light with wavelengths of 520 to 540 Å, iii. Modulators of red-yellow, stimulated by light, with wavelengths of 580 to 600 Å., If green light falls on retina, modulators of green, are stimulated and other two are less affected. Thus,, according to Granit, the dominators are responsible, for brightness or intensity of light, both in dark-adapted
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Chapter 170 t Color Vision 1001, (rods) and light-adapted (cones) eyes. The modulators, are responsible for color vision in light-adapted eyes., 4. HARTRIDGE POLYCHROMATIC THEORY, According to this theory, human retina has seven types, of receptors. All the seven receptors are divided into, three units:, , has more cones so, it is more sensitive to color. In, extrafoveal regions, cones are mingled with rods., Retinal area sensitive to blue is largest and to, green is smallest. Red comes next to blue and then, comes yellow. All the color areas of retina are mapped, out by using perimeter., , CONTRAST EFFECTS, , First Unit, , SIMULTANEOUS CONTRAST, , First unit is a tricolor unit consisting of receptors for, orange, green and blue., , Simultaneous contrast is the effect that intensifies, the contrast (difference) between two colors, which, are placed against each other. When black is placed, against white or white against black, these two colors, set one another off, i.e. the black looks blacker and the, white looks whiter. Similarly, the green is enhanced by, red and red by green., Maximum effect of simultaneous contrast is obtained, when the complementary colors are paired. Reason, for simultaneous contrast is that, the stimulation of an, area of retina by one color modifies the response in, the surrounding or neighboring areas. It increases the, sensitivity to other colors in the surrounding receptors., This action is probably due to horizontal cells., , Second Unit, Second unit is a dicolor unit with receptors for yellow, and blue colors. Receptors for yellow and blue are, complementary to each other., Third Unit, Third unit is another dicolor unit with red and bluegreen receptors., 5. HERING’S THEORY OF OPPOSITE COLORS, According to Hering, retina has three photochemical, substances. Each substance produces the sensation, of a particular color by its breakdown or resynthesis., First Substance, First substance is white-black substance. Its breakdown causes sensation of white and resynthesis, causes sensation of black., Second Substance, Second substance is yellow-blue substance. Its breakdown causes sensation of yellow and resynthesis, causes sensation of blue., Third Substance, Third substance is red-green substance. Its breakdown causes sensation of red and resynthesis causes, sensation of green., This theory explains the successive contrast and, afterimages, but not the simultaneous sensation of, antagonistic colors., , COLOR SENSITIVE AREAS IN RETINA, Peripheral part of retina is devoid of cones and is, insensitive to color and gives sensation of white, black, and grey only. Central portion of retina, fovea centralis, , SUCCESSIVE CONTRAST, Successive contrast is the effect of previously viewed, color field on the appearance of currently viewed color, field. When a person looks at a green object after, looking at a bright red, the green object appears to be, more greenish. There is an increase in the sensitivity, to the complementary color., Reason for successive contrast is that, the stimulation of an area of retina modifies its sensitivity to the, successive stimuli. Thus, there is an increase in the, sensitivity to the second color., , AFTERIMAGE, Afterimage is the phenomenon in which retention of, image occurs even after cessation of light stimulus., After looking at a bright object, if the eyes are closed,, the image remains more distinct for some time and then, fades away gradually. Afterimage is of two types:, 1. POSITIVE AFTERIMAGE, Positive afterimage is an afterimage persisting after, closure of eyes or turning towards a dark background., After looking at a bright object, if the eyes are closed or, fixed on a black surface, the afterimage appears to be, bright and with same color of the object.
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1002 Section 11 t Special Senses, 2. NEGATIVE AFTERIMAGE, Negative afterimage is an afterimage that persists while, turning towards a bright background. After looking, at bright object, if the eyes are fixed on white surface, (instead of closing or fixing on a black surface), the, afterimage appears in complementary color. Reason, for negative afterimage is the persistence of activity in, retina, even after the particular stimulus ceases to act., , APPLIED PHYSIOLOGY –, COLOR BLINDNESS, Color blindness is the failure to appreciate one or more, colors. It is common in 8% of males and only in 0.4% of, females, as mostly the color blindness is an inherited, sex-linked recessive character. In addition to hereditary, conditions, color blindness occurs due to acquired, conditions also such as ocular diseases or injury or, disease of retina., The term ‘color blind’ does not mean that objects, are seen only in black and white. Total color blindness, is very rare. There are many types and degrees of, color blindness. The most appropriate term for color, blindness is deficiency of color vision., CAUSES FOR ACQUIRED, COLOR BLINDNESS, 1. Trauma, Injury to eye due to accidents or strokes results in color, blindness., 2. Chronic Diseases, Color blindness is caused by chronic diseases such as:, i. Glaucoma, ii. Degeneration of macula of eye, iii. Retinitis, iv. Sickle cell anemia, v. Leukemia, vi. Diabetes, vii. Liver diseases, viii. Parkinson disease, ix. Alzheimer disease, x. Multiple sclerosis., 3. Drugs, Frequent use of some drugs leads to color blindness:, i. Antibiotics, ii. Antihypertensive drugs, iii. Antituberculosis drugs, , iv. Barbiturates, v. Drugs used to treat psychological problems, and neural disorders., 4. Toxins, Industrial toxins or strong chemicals cause color, blindness. Common substances causing color, blindness are:, i. Fertilizers, ii. Carbon monoxide, iii. Carbon disulfide, iv. Chemicals with high lead content., 5. Alcoholism, Chronic alcoholism results in color blindness., 6. Aging, Color blindness can occur after 60 years of age due to, various changes in eye., CLASSIFICATION OF COLOR BLINDNESS, Based on Young-Helmholtz trichromatic theory, color, blindness is classified into three types (Fig. 170.1):, 1. Monochromatism, Monochromatism is the condition characterized by, total inability to perceive color. It is also called total, color blindness or achromatopsia. Monochromatism, is very rare. Persons with monochromatism are called, monochromats. Retina of monochromats is totally insensitive to color and they see the whole spectrum, in only black, white and different shades of grey. So,, their vision is similar to black and white photography., Monochromatism is divided into two types:, i. Rod monochromatism, Rod monochromatism is the condition in which cones, are functionless and the vision depends purely on rods., So, rod monochramats are totally color blind. They, are dazzled by light but definitely are not blind during, daylight. Their visual acuity is lowered and foveal, vision is absent which results in central scotoma., Central scotoma is the formation of big blind spot in, fovea centralis due to the non-functioning of cones., Rods are also absent in fovea., ii. Cone monochromatism, Cone monochromatism is the condition in which, vision depends upon one single type of cone. Central, scotoma does not occur in this condition.
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Chapter 170 t Color Vision 1003, , FIGURE 170.1: Color blindness, , 2. Dichromatism, , 3. Trichromatism, , Dichromatism is the color blindness in which the subject, can appreciate only two colors. Persons with this defect, are called dichromats. They can match entire spectrum, of colors by only two primary colors because the, receptors for third color are defective. The defects are, classified into three groups:, , Trichromatism is the color blindness in which intensity, of one of the primary colors cannot be appreciated, correctly though the affected persons are able to, perceive all the three colors. Persons with this defect, are called trichromats. Even the dark shades of one, particular color look dull for them. Trichromatism is, classified into three types:, , i. Protanopia, , i. Protanomaly, , Protanopia is the type of dichromatism caused by the, defect in receptor of first primary color, i.e. red. So,, the red color cannot be appreciated. Persons having, protanopia are called protanopes. They use blue and, green to match the colors. Thus, they confuse red with, green., , Protanomaly is the type of trichromatism in which the, perception for red is weak. So to appreciate red color,, the person requires more intensity of red than a normal, person., , ii. Deuteranopia, Deuteranopia is the dichromatism caused by the, defect in receptor of second primary color, i.e. green., Deuteranopes use blue and red colors and they cannot, appreciate green color., iii. Tritanopia, Tritanopia is the dichromatism caused by the defect, in receptor of third primary color, i.e. blue. Tritanopes, use red and green colors and they cannot appreciate, blue color., , ii. Deuteranomaly, Deuteranomaly is the trichromatism in which the perception for green is weak., iii. Tritanomaly, Tritanomaly is the trichromatism with weak perception, for blue., TESTS FOR COLOR BLINDNESS, Three methods are available to determine the color, blindness:, 1. By using Ishihara color charts, 2. By using Holmgren colored wool, 3. By using Edridge-Green lantern.
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Errors of Refraction, , Chapter, , 171, , AMETROPIA, , , , MYOPIA OR SHORT SIGHTEDNESS, HYPERMETROPIA OR LONG SIGHTEDNESS, , ANISOMETROPIA, ASTIGMATISM, , , , , CAUSE, TYPES, CORRECTION, , PRESBYOPIA, , , , CAUSES, CORRECTION, , AMETROPIA, , Cause, , The eye with normal refractive power is called emmetropic eye and the condition is called emmetropia. Any, deviation in the refractive power from normal condition,, resulting in inadequate focusing on retina is called, ametropia and the eye is called ametropic eye. The, defect is due to the change in shape of the eyeball., Ametropia is of two types:, 1. Myopia, 2. Hypermetropia., , In myopia, the refractive power of lens is usually, normal. But, the anteroposterior diameter of the, eyeball is abnormally long. Therefore, the image is, brought to focus a little in front of retina. Light rays,, after coming to a focus, disperse again so, a blurred, image is formed upon retina., , MYOPIA OR SHORT SIGHTEDNESS, Myopia is the eye defect characterized by the inability, to see the distant object. It is otherwise called short, sightedness because the person can see near objects, clearly but not the distant objects. In emmetropia, the, far point is infinite. In myopia, the near vision is normal, but the far point is not infinite, i.e. it is at a definite, distance (Fig. 171.1 and Table 171.1). In extreme, conditions, it may be only a few centimeter away from, the eye (myo = half closed; ops = eye)., , Correction, In myopic eye, in order to form a clear image on the, retina, the light rays entering the eye must be divergent, and not parallel. Thus, the myopic eye is corrected by, using a biconcave lens. Light rays are diverged by the, concave lens before entering the eye (Fig. 171.1)., HYPERMETROPIA OR LONG SIGHTEDNESS, Hypermetropia is the eye defect characterized by the, inability to see near object. It is otherwise known as long, sightedness because the person can see the distant, objects clearly but not the near objects. It is also called, hyperopia. In this defect, distant vision is normal but,, near vision is affected (metras = measure).
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Chapter 171 t Errors of Refraction 1005, Cause, , ANISOMETROPIA, , Hypermetropia is due to decreased anteroposterior, diameter of the eyeball. So, even though the refractive, power of lens is normal, the light rays are not converged, enough to form a clear image on retina, i.e. the light, rays are brought to a focus behind retina. It causes a, blurred image of near objects. Hypermetropia occurs, in childhood, if the eyeballs fail to develop the correct, size. It is common in old age also., , Anisometropia is the condition in which the two eyes, have unequal refractive power. It is corrected by using, different appropriate lens for each eye (Table 171.1)., , Correction, Hypermetropia is corrected by using biconvex lens., Light rays are converged by convex lens before, entering the eye (Fig. 171.1)., , ASTIGMATISM, Astigmatism is the condition in which light rays are not, brought to a sharp point upon retina. It is the common, optical defect. This defect is present in all eyes., When it is moderate, it is known as physiological, astigmatism. When it is well marked, it is considered, abnormal. For example, the stars appear as small, dots of light to a person with normal eye. But in, astigmatism, the stars appear as radiating short lines, of light (A = not; stigma = point)., CAUSE OF ASTIGMATISM, Light rays pass through all meridians of a lens. In a, normal eye, lens has approximately same curvature in, all meridians. So, the light rays are refracted almost, equally in all meridians and brought to a focus., If the curvature is different in different meridians,, vertical, horizontal and oblique, the refractive power is, also different in different meridians. The meridian with, greater curvature refracts the light rays more strongly, than the other meridians. So, these light rays are, brought to a focus in front of the light rays, which pass, through other meridians. Such irregularity of curvature, of lens causes astigmatism., TYPES OF ASTIGMATISM, Astigmatism is of two types:, 1. Regular astigmatism, 2. Irregular astigmatism., 1. Regular Astigmatism, In regular type of astigmatism, the refractive power is, unequal in different meridians because of alteration, of curvature in one meridian. But, it is uniform in all, points throughout the affected meridian., 2. Irregular Astigmatism, , FIGURE 171.1: Errors of refraction, , In irregular type of astigmatism, the refractive power, is unequal not only in different meridians, but it is also, unequal in different points of same meridian.
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1006 Section 11 t Special Senses, TABLE 171.1: Errors of refraction, Type of error, , Cause, , Correction, , Myopia, , Increase in anteroposterior diameter of the eyeball, , Biconcave lens, , Hypermetropia, , Decrease in anteroposterior diameter of the eyeball, , Biconvex lens, , Anisometropia, , Difference in refractive power of both eyes, , Separate lens (biconcave or, biconvex) for each eye as, required, , Astigmatism, , Refractory power of lens is different in different meridians, , Regular astigmatism, , Refractory power of lens is unequal in different meridians, but uniform in one single meridian, , Irregular astigmatism, , Refractory power of lens is unequal in different meridians, as well as in different points in same meridian, , Presbyopia, , Loss of elasticity in lens and weakness of ocular muscles, due to old age, , CORRECTION OF ASTIGMATISM, Astigmatism is corrected by using cylindrical glass lens, having the convexity in the meridians, corresponding, to that of lens of eye having a lesser curvature, i.e., if the horizontal curvature of lens is less, the person, should use cylindrical glass lens with the convexity in, horizontal meridian., , PRESBYOPIA, Presbyopia is the condition characterized by progressive diminished ability of eyes to focus on near, objects with age. It is due to the gradual reduction in, the amplitude of accommodation. It progresses as the, age advances (presbyos = old; ops = eye). Presbyopia, starts developing after middle age. In presbyopia, the, distant vision is unaffected. Only the near vision is, , Cylindrical lens, , Biconvex lens, , affected. The near point is away from eye. In presbyopia,, the anterior curvature of lens does not increase during, near vision. So, the light rays from near objects are not, brought to focus on retina., CAUSES OF PRESBYOPIA, 1. Decreased elasticity of lens is because of the, physical changes in lens and its capsule during, old age. So, the anterior curvature is not increased, during near vision., 2. Decreased convergence of eyeballs due to the, concomitant weakness of ocular muscles in old, age., CORRECTION OF PRESBYOPIA, Presbyopia is corrected by using biconvex lens.
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Chapter, , Structure of Ear, , 172, , EXTERNAL EAR, , , , AURICLE OR PINNA, EXTERNAL AUDITORY MEATUS, , MIDDLE EAR, , , , , AUDITORY OSSICLES, AUDITORY MUSCLES, EUSTACHIAN TUBE, , INTERNAL EAR, , , , , COCHLEA, COMPARTMENTS OF COCHLEA, ORGAN OF CORTI, , EXTERNAL EAR, , EXTERNAL AUDITORY MEATUS, , Ear consists of three parts, namely external ear,, middle ear and internal ear (Fig. 172.1)., External ear is formed by two parts:, 1. Auricle or pinna, 2. External auditory meatus., , External auditory meatus starts from the concha and, extends inside as a slightly curved canal, with a length, of about 55 mm., Meatus consists of two parts:, i. Outer cartilaginous part, ii. Inner bony part., , AURICLE OR PINNA, Auricle or pinna of the external ear consists of, fibrocartilaginous plate covered by connective tissue, and skin. This plate is characteristically folded and, ridged. Skin covering this plate is thin and contains, many fine hairs and sebaceous glands. On the posterior, surface of auricles, many sweat glands are present., In many animals, auricle can be moved and turned, to locate the source of sound or the auricle can be, folded to avoid unwanted sound. But in man, extrinsic, and intrinsic muscles of auricles are rudimentary and, the movement is not possible. The depression of, auricle, which forms the orifice of external auditory, meatus, is called concha., , i. Outer Cartilaginous Part, Cartilaginous part is the initial part of external auditory, meatus and is made up of cartilage. It is covered, by thick skin, which contains stiff hairs. These hairs, prevent the entry of foreign particles., Large sebaceous glands and ceruminous glands, are also present in the skin covering this portion. These, glands are coiled and tubular in nature and open on, the surface of the skin. Columnar epithelial cells of the, glands contain brown pigment granules and fat droplets., Secretions of ceruminous glands, sebaceous glands, and desquamated epithelial cells form the earwax.
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1008 Section 11 t Special Senses, , FIGURE 172.1: Diagram showing the structure of ear, , ii. Inner Bony Part, Inner part of the external auditory meatus is also, covered by skin, which adheres closely to periosteum., Only sebaceous glands are present here. Small fine, hairs are present on the superior wall of the canal. Skin, covering this portion is continuous with cuticular layer of, tympanic membrane., , MIDDLE EAR, Middle ear or tympanic cavity is a small, narrow, ir, regular, laterally compressed chamber, situated within, the temporal bone. It is also known as tympanum. It is, separated from external auditory meatus by tympanic, membrane., , Middle ear consists of the following structures:, 1. Auditory ossicles, 2. Auditory muscles, 3. Eustachian tube., Tympanic Membrane, Tympanic membrane is a thin, semitransparent mem, brane, which separates the middle ear from external, auditory meatus. Periphery of the membrane is fixed to, tympanic sulcus in the surrounding bony ring, by means, of fibrocartilage (Fig. 172.2)., Structure of Tympanic Membrane, Tympanic membrane is formed by three layers:, 1. Lateral cutaneous layer, which is the continuation, of the skin of auditory meatus, , 2. Intermediate fibrous layer, which contains coll, agenous fibers, 3. Medial mucus layer or tympanic mucosa, which, is composed of single layer of cuboidal epithelial, cells., AUDITORY OSSICLES, Auditory ossicles are the three miniature bones,, which are arranged in the form of a chain, extending, across the middle ear from the tympanic membrane, to oval window (Fig. 172.2)., Auditory ossicles are:, i. Malleus, ii. Incus, iii. Stapes., i. Malleus, Malleus is otherwise called hammer. It has a handle,, head and neck. Hand is called manubrium and it is, attached to tympanic membrane. Neck extends from, handle to the head. Head or capitulum articulates with, the body of incus., ii. Incus, Incus is also known as anvil. It looks like a premolar, tooth. Incus has a body, one long process and one, short process. Anterior surface of the body articulates, with the head of malleus. The short process is, attached to a ligament. The long process runs parallel, to handle of malleus. Tip of the long process is like a, knob called lenticular process and it articulates with, the next bone, stapes.
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Chapter 172 t Structure of Ear 1009, ii. Stapedius, Stapedius is the smallest skeletal muscle in human body, with a length of just over 1 mm. It lies in a conical bony, cavity, on the posterior wall of the tympanic cavity., Origin, insertion and nerve supply, Stapedius arises from interior pyramid of tympanic, cavity. Its tendon is inserted into the posterior surface of, neck of stapes. It is supplied by branch of facial nerve., Function, , FIGURE 172.2: Tympanic membrane and auditory ossicles, , iii. Stapes, Stapes is also called stirrup. It is the smallest bone in the, body. It has a head, neck, anterior crus, posterior crus, and a footplate. Head articulates with incus. Footplate, fits into oval window., AUDITORY MUSCLES, Two skeletal muscles are attached to ossicles:, i. Tensor tympani, ii. Stapedius., i. Tensor Tympani, Tensor tympani is larger of the two muscles of, tympanic cavity., Origin, insertion and nerve supply, Tensor tympani arises from cartilaginous portion of, eustachian tube (see below), adjacent to great wing of, sphenoid bone and osseous canal. Its tendon is inserted, on manubrium of malleus, which is in turn attached, to tympanic membrane. Thus, the tensor tympani is, attached to tympanic membrane through malleus. It is, supplied by mandibular division trigeminal nerve., , Stapedius prevents excess movements of stapes., When it contracts, it pulls the neck of stapes back, wards and reduces the movement of footplate against, the fluid in cochlea. Paralysis of stapedius allows, wider range of oscillation of stapes, leading to hyperreaction of auditory ossicles to sound vibrations. This, condition is called hyperacusis. Paralysis of stapedius, occurs in the lesion of facial nerve., Tympanic Reflex, Tympanic reflex is an attenuation reflex characterized, by involuntary contraction of tensor tympani and, stapedius muscles, in response to a loud noise. It has, a latent period of 40 to 80 millisecond., When both the muscles contract, manubrium of, malleus moves inward and stapes is pulled outward., These two actions result in stiffness of auditory ossicles,, so that the transmission of sound is decreased., Significance of tympanic reflex, i. Tympanic reflex protects the tympanic, membrane from being ruptured by loud sound, ii. It also prevents fixation of footplate of stapes,, against oval window, during exposure to loud, sound, iii. It helps to protect the cochlea from damaging, effects of loud sounds. Contraction of tensor, tympani and stapedius during exposure to, loud sound develops stiffness of the auditory, ossicles so that, the transmission of sound into, cochlea is decreased., , Function, Tensor tympani muscle pulls and keeps the tympanic, membrane stretched or tensed constantly. This, constant stretching of tympanic membrane is essential, for the transmission of sound waves, which may reach, any part of the tympanic membrane. Paralysis of, tensor tympani causes hearing impairment., , EUSTACHIAN TUBE, Eustachian tube or the auditory tube is the flattened, canal extending from the anterior wall of middle ear, to nasopharynx. Its upper part is surrounded by, the bony wall and the lower part is surrounded by, fibrocartilaginous plate.
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1010 Section 11 t Special Senses, Eustachian tube connects middle ear with posterior, part of nose and forms the passage of air between, middle ear and atmosphere. So, the pressure on both, sides of tympanic membrane is equalized., , INTERNAL EAR, Internal ear or labyrinth is a membranous structure,, enclosed by a bony labyrinth in petrous part of temporal, bone. It consists the sense organs of hearing and, equilibrium. Sense organ for hearing is the cochlea, and the sense organ for equilibrium is the vestibular, apparatus. Vestibular apparatus is already explained, in Chapter 158., COCHLEA, Cochlea is a coiled structure like a snail’s shell, (cochlea = snail’s shell). It consists of two structures:, 1. Central conical axis formed by spongy bone called, modiolus, , 2. Bony canal or tube, which winds around the, modiolus., In man, the bony canal makes two and a half, turns, starting from the base of the cochlea and ends, at the top (apex) of cochlea. End of the canal is called, cupula. Base of modiolus forms the bottom of internal, auditory meatus, through which cochlear nerve fibers, pass and enter the modiolus. Thus, a section through, the axis of cochlea reveals the central bony pillar,, modiolus and periotic or osseous canal, which coils, around the modiolus., From modiolus, a bony ridge called osseous spiral, lamina projects into the canal, winding around modiolus, like the thread of a screw. Spiral lamina follows the, spiral turns of cochlea and ends at the cupula in a, hookshaped process called hamulus., , brane is also called membranous spiral lamina., Along the basilar membrane are twenty thousand, to thirty thousand tiny fibers that are called basilar, fibers. Each fiber has different size and shape., Fibers near the oval window are short and stiff. While, approaching towards helicotrema (see below) the, basilar fibers gradually become longer and soft., 2. Vestibular Membrane, Vestibular membrane is also known as Reissner, membrane and it is a thin membrane. It is placed, obliquely between the upper surface of osseous spiral, lamina and upper part of spiral ligament., Basilar membrane and vestibular membrane divide, the spiral canal of cochlea into three compartments, called scalae (Fig. 172.3)., Compartments of spiral canal of cochlea:, i. Scala vestibuli, ii. Scala tympani, iii. Scala media., All the three compartments are filled with fluid., Scala vestibuli and scala tympani contain perilymph., Scala media is filled with endolymph., i. Scala vestibuli, Scala vestibuli lies above scala media. It arises from, oval window (fenestra vestibuli), which is closed by the, , COMPARTMENTS OF COCHLEA, Two membranous partitions extend between the, osseous spiral lamina and outer wall of the spiral, canal. Both the membranes divide the spiral canal of, cochlea into three compartments., Membranes of cochlea:, 1. Basilar membrane, 2. Vestibular membrane., 1. Basilar Membrane, Basilar membrane is a connective tissue membrane., It stretches from the tip of the osseous spiral lamina, to tough dense fibrous band called spiral ligament,, which lines the outer wall of the canal. Basilar mem, , FIGURE 172.3: Crosssection of spiral canal of cochlea
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Chapter 172 t Structure of Ear 1011, footplate of stapes. It follows the bony canal up to, its apex. At the apex, it communicates with the scala, tympani through a small canal called helicotrema., ii. Scala tympani, Scala tympani lies below scala media. It is parallel to, scala vestibuli and ends at the round window. Round, window is closed by a strong thin membrane known, as secondary tympanic membrane., iii. Scala media, Scala media is otherwise called cochlear duct,, membranous cochlea or otic cochlea. It is a triangular, compartment enclosed by basilar and vestibular, membranes. It ends blindly at the apex and at the base, of cochlea. A slender ductus reuniens arises from the, basal end and connects scala media with the saccule, of otolith organ., Scala media is formed by upper, outer and lower, walls. Upper wall or vestibular wall is formed by, vestibular membrane. Outer wall is formed by spiral, ligament, which is the thickening of periosteum., Lower wall is called tympanic wall. It is formed by, basilar membrane (membranous spiral lamina) and a, part of osseous spiral lamina. Scala media stretches, between the tip of osseous spiral lamina and spiral, ligament., Basilar membrane consists of straight unbranched, connective tissue fibers, which are called basilar fibers, or the auditory fibers. On the upper surface of the, basilar membrane, epithelial cells are arranged in the, form a special structure called the organ of Corti. It is, the sensory part of cochlea., ORGAN OF CORTI, Organ of Corti is the receptor organ for hearing. It is, the neuroepithelial structure in cochlea (Fig. 172.4)., Situation and Extent, , of organ of Corti are arranged in order from center, towards the periphery of the cochlea., Cells of organ of Corti:, 1. Border cells, 2. Inner hair cells, 3. Inner phalangeal cells, 4. Inner pillar cells, 5. Outer pillar cells, 6. Outer phalangeal cells, 7. Outer hair cells, 8. Cells of Hensen, 9. Cells of Claudius, 10. Tectorial membrane and lamina reticularis., 1. Border Cells, Border cells are the slender columnar cells, arranged, in a single layer on the tympanic lip along the inner, side of inner hair cells. Surfaces of the border cells, have cuticle., 2. Inner Hair Cells, Inner hair cells are flaskshaped cells and are broader, than the outer hair cells. Inner hair cells are arranged in, a single row and occupy only the upper part of epithelial, layer. Rounded base of each cell rests on the adjacent, supporting cells called the inner phalangeal cell. Surface, of the inner hair cell bears a cuticular plate and a number, of short stiff hairs, which are called stereocilia. Each, hair cell has about 100 sterocilia. One of the sterocilia, is larger and it is called kinocilium. Stereocilia are in, contact with the tectorial membrane. Inner hair cells and, outer hair cells together form the receptor cells. Sensory, nerve fibers are distributed around the hair cells. Both, inner hair cells and outer hair cells have afferent and, efferent nerve fibers (Chapter 173)., 3. Inner Phalangeal Cells, , gelatinous tectorial membrane., , Inner phalangeal cells are the supporting cells of inner, hair cells and are arranged in a row along the inner, surface of inner pillar cells. Their bases rest on the, basilar membrane. Cuticular plate of cells (formed by, the lower portion of cells) look like the finger bones,, phalanges., , Structure, , 4 and 5. Inner and Outer Pillar Cells – Rods of Corti, , Organ of Corti is made up of sensory elements called, hair cells and various supporting cells. All the cells, , Inner and outer pillar cells are called rods of Corti., Each pillar cell has a broader base, an elongated body, , Organ of corti rests upon the lip of osseous spiral, lamina and basilar membrane. It extends throughout, the cochlear duct, except for a short distance on, either end. Roof of the organ of Corti is formed by
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1012 Section 11 t Special Senses, , FIGURE 172.4: Organ of Corti, , or pillar and a head at the tip of pillar. Bases of inner, pillar cells are close to the lip of osseous spiral lamina, (tympanic lip), whereas the bases of outer pillar cells, are close to basilar membrane. Pillars of inner and, outer pillar cells slope towards each other and their, heads articulate. Thus, the pillars of cells form series of, arches, which enclose a triangular tunnel called inner, tunnel or tunnel of Corti., 6. Outer Phalangeal Cells, Outer phalangeal cells or the cells of Deiters are the, supporting cells of outer hair cells. Outer phalangeal, cell is the tall columnar cell. It sends stiff phalangeal, processes upward between the hair cells, to form the, part of lamina reticularis., Rows of outer phalangeal cells vary in different, regions of cochlear duct like the outer hair cells, i.e., from three to five rows. Between the inner most outer, phalangeal cells and outer pillar cells, is a fluid space, known as the space of Nuel., 7. Outer Hair Cells, Outer hair cells are the columnar cells occupying, the superficial part of epithelium of organ of Corti., Their bases are supported by outer phalangeal cells., Structure of outer hair cells is similar to that of inner, hair cells (see above)., , 8. Cells of Hensen, Cells of Hensen are tall columnar cells forming the, outer border cells of organ of Corti. These cells are, arranged in several rows on basilar membrane, lateral, to outer phalangeal cells. The space between outer, phalangeal cells and cells of Hensen is called outer, tunnel., 9. Cells of Claudius, Cells of Claudius are cuboidal in nature and line the, lower surface of external spiral sulcus. In certain, areas, some groups of cells are present between the, cells of Claudius and basilar membrane. These cells, are called Boettcher cells., 10. Tectorial Membrane and Lamina Reticularis, Tectorial membrane extends from vestibular lip to the, level of cells of Hensen. It forms the roof of organ of, Corti. It is in contact with the processes of hair cells., It is assumed that the processes of hair cells are, stimulated by the movements of tectorial membrane,, in relation to vibrations in endolymph., Cuticular plates of all the supporting cells, collectively form a reticular membrane, which is known, as lamina reticularis. It covers the organ of Corti. It, looks like a mosaic and has rows of holes, through, which the heads of hair cells are inserted.
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Chapter, , Auditory Pathway, , , , , , , , , 173, , INTRODUCTION, RECEPTORS, FIRST ORDER NEURONS, SECOND ORDER NEURONS, THIRD ORDER NEURONS, CORTICAL AUDITORY CENTERS, APPLIED PHYSIOLOGY – EFFECT OF LESION, , INTRODUCTION, Fibers of auditory pathway pass through cochlear, division of vestibulocochlear nerve (VIII cranial nerve)., It is also known as auditory nerve. Major part of the, auditory pathway lies in medulla oblongata, midbrain, and thalamic region., Higher center for hearing is in temporal lobe of, cerebral cortex, where the fibers of auditory pathway, finally terminate. Fibers are both crossed and uncrossed, so that each cochlea is represented in the, cortex on both sides., , RECEPTORS, Hair cells in organ of Corti are the receptors of the, , auditory sensation. Hair cells are of two types, outer hair, cell and inner hair cell. All the hair cells are innervated by, afferent and efferent nerve fibers. Afferent nerve fibers, from the hair cells form auditory nerve (see below)., , (axons) leave the ear as cochlear nerve fibers and, enter medulla oblongata. In medulla oblongata, these, fibers divide into two groups, which end on ventral, cochlear nucleus and dorsal cochlear nucleus of the, same side in medulla oblongata., Efferent Nerve Fibers to Hair Cells, Efferent nerve fibers of hair cells arise from superior, olivary nucleus. Fibers from this nucleus reach the, hair cells by passing through the ventral and dorsal, cochlear nuclei and cochlear nerve of the same side., Efferent nerve fiber to outer hair cell terminates, directly on the cell body and controls the motility of, this cell (Chapter 174). Efferent nerve fiber to inner, hair cell terminates on the auditory (afferent) nerve, fiber, where it leaves the inner hair cell. It controls the, impulse output from this hair cell., , SECOND ORDER NEURONS, FIRST ORDER NEURONS, First order neurons of auditory pathway are the bipolar, cells of spiral ganglion, situated in modiolus of cochlea, (Fig. 173.1)., Peripheral short processes (dendrites) of the, bipolar cells are distributed around hair cells of organ, of Corti as afferent nerve fibers. Their long processes, , Neurons of dorsal and ventral cochlear nuclei in the, medulla oblongata form the second order neurons of, auditory pathway. Axons of the second order neurons, run in four different groups:, 1. First group of fibers cross the midline and run to the, opposite side, to form trapezoid body. Fibers from, trapezoid body go to the superior olivary nucleus.
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1014 Section 11 t Special Senses, , FIGURE 173.1: Auditory pathway. Blue = First order neuron, Red = Second order neuron,, Green =Third order neuron, Black = Auditory radiation., , 2. Second group of fibers terminate at superior olivary, nucleus of same side via trapezoid body of the, same side, 3. Third group of fibers run in lateral lemniscus of, the same side and terminate in nucleus of lateral, lemniscus of same side, 4. Fourth group of fibers run into reticular formation,, cross the midline as intermediate trapezoid fibers, and finally join the nucleus of lateral lemniscus of, opposite side., , THIRD ORDER NEURONS, Third order neurons are in the superior olivary nuclei, and nucleus of lateral lemniscus. Fibers of the third, order neurons end in medial geniculate body, which, forms the subcortical auditory center., Fibers from medial geniculate body go to the, temporal cortex, via internal capsule as auditory, , radiation. Some fibers from medial geniculate body go, to inferior colliculus of tectum in midbrain. The fibers, , of auditory radiation are involved in reflex movement of, head, in response to auditory stimuli., , CORTICAL AUDITORY CENTERS, Cortical auditory centers are in the temporal lobe of, cerebral cortex (Chapter 152)., Auditory areas are:, 1. Primary auditory area, which includes area 41, area, 42 and Wernicke area, 2. Secondary auditory area or auditopsychic area,, which includes area 22., Areas 41 and 42 are the primary auditory areas, situated in the anterior transverse gyrus and lateral, surface of superior temporal gyrus. Wernicke area, is in upper part of superior temporal gyrus, posterior, to areas 41 and 42. Area 22 occupies the superior, temporal gyrus.
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Chapter 173 t Auditory Pathway 1015, FUNCTIONS OF CORTICAL, AUDITORY CENTERS, Cortical auditory centers are concerned with the perception of auditory impulses, analysis of pitch and intensity of sound and determination of source of sound., Areas 41 and 42 are concerned with the perception, of auditory impulses only. However, analysis and, interpretation of sound are carried out by Wernicke, area, with the help of area 22., , APPLIED PHYSIOLOGY –, EFFECT OF LESION, 1. Lesion of cochlear nerve causes deafness of the ear, 2. Unilateral lesion of auditory pathway, above the, level of cochlear nuclei causes diminished hearing, 3. Degeneration of hair cells in the organ of Corti leads, to presbycusis. Presbycusis is the gradual loss of, hearing. It is common in old age., 4. Lesion in superior olivary nucleus results in poor, localization of sound.
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Mechanism of Hearing, , Chapter, , 174, , INTRODUCTION, ROLE OF EXTERNAL EAR, ROLE OF MIDDLE EAR, , , , , ROLE OF TYMPANIC MEMBRANE, ROLE OF AUDITORY OSSICLES, ROLE OF EUSTACHIAN TUBE, , ROLE OF INNER EAR, , , , TRAVELING WAVE, EXCITATION OF HAIR CELLS, , ELECTRICAL EVENTS DURING PROCESS OF HEARING, , , , , , , SOUND TRANSDUCTION, COCHLEAR MICROPHONIC POTENTIAL, ROLE OF HAIR CELLS, ENDOLYMPHATIC POTENTIAL, ACTION POTENTIAL IN AUDITORY NERVE FIBER, , PROPERTIES OF SOUND, APPRECIATION OF PITCH OF THE SOUND – THEORIES OF HEARING, , , , THEORIES OF FIRST GROUP, THEORIES OF SECOND GROUP, , APPRECIATION OF LOUDNESS OF SOUND, LOCALIZATION OF SOUND, , INTRODUCTION, Sound waves travel through external auditory meatus, and produce vibrations in the tympanic membrane., Vibrations from tympanic membrane travel through, malleus and incus and reach the stapes resulting in the, movement of stapes. Movements of stapes produce, vibrations in the fluids of cochlea. These vibrations, stimulate the hair cells in organ of Corti. This, in, turn, causes generation of action potential (auditory, impulses) in the auditory nerve fibers. When auditory, impulses reach the cerebral cortex, the perception of, hearing occurs., Thus, during the process of hearing, ear converts, energy of sound waves into action potentials in, , auditory nerve fibers. This process is called sound, transduction., , ROLE OF EXTERNAL EAR, External ear directs the sound waves towards, tympanic membrane. Sound waves produce pressure, changes over the surface of tympanic membrane., Accumulation of wax prevents conduction of sound., In many animals, the auricle (pinna) can be turned to, locate the source of sound. Auricle can be folded to, avoid unwanted sound. But in man, the extrinsic and, intrinsic muscles of auricle are rudimentary and the, movement is not possible.
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Chapter 174 t Mechanism of Hearing 1017, , ROLE OF MIDDLE EAR, ROLE OF TYMPANIC MEMBRANE, Due to the pressure changes produced by sound, waves, tympanic membrane vibrates, i.e. it moves in, and out of middle ear. Thus, tympanic membrane acts, as a resonator that reproduces the vibration of sound., ROLE OF AUDITORY OSSICLES, Vibrations set up in tympanic membrane are, transmitted through the malleus and incus and reach, the stapes, causing to and fro movement of stapes, against oval window and against perilymph present in, scala vestibuli of cochlea., Impedance Matching, Impedance matching is the process by which tympanic, membrane and auditory ossicles convert the sound, energy into mechanical vibrations in cochlear fluid with, minimum loss of energy by matching the impedance, offered by fluid., Impedance means obstruction or opposition to the, passage of sound waves. When sound waves reach inner, ear, the fluid (perilymph) in cochlea offers impedance,, i.e. the fluid resists the transmission of sound due to its, own inertia. Tympanic membrane and auditory ossicles effectively reduce the sound impedance., Sound waves are conducted from external ear to, inner ear, with an impedance of only 40%. Remaining, 60% of sound energy developed in tympanic membrane, is transmitted to cochlear fluid by the ossicles. Thus,, along with the help of tympanic membrane, ossicles, match the impedance offered by fluid to a great extent., It is because, the ossicles act like a lever system so, that stapes exerts a greater force (pressure) against the, cochlear fluid. This results in generation of vibrations in, the cochlear fluid. The increased force is very essential, to set up the vibrations in cochlear fluid because of, higher inertia of the fluid., Force exerted by footplate of stapes on cochlear, fluid is 17 to 22 times greater than the force exerted, by sound waves at the tympanic membrane. It is, because of two structural features of ossicles:, 1. Head of malleus is longer than long process of, incus so that a higher force is generated in small, structure, 2. Surface area of tympanic membrane (55 sq mm), is larger compared to that of footplate of stapes, , (3.2 sq mm). So the pressure increases when force, is applied to small area., Thus, the tympanic membrane and the auditory, ossicles are capable of converting the sound energy, into mechanical vibrations in cochlear fluid with, minimum loss of energy., Significance of impedance matching, Impedance matching is the most important function, of middle ear. Because of impedance matching the, sound waves (stimuli) are transmitted to cochlea with, minimum loss of intensity. Without impedance matching, conductive deafness occurs., Types of Conduction, Conduction of sound from external ear to internal ear, through middle ear occurs by three routes:, 1. Ossicular conduction, 2. Air conduction, 3. Bone conduction., 1. Ossicular conduction, Ossicular conduction is the conduction of sound waves, through middle ear by auditory ossicles. In normal, conditions, the sound waves are conducted through, auditory ossicles., 2. Air conduction, Air conduction is the conduction of sound waves, through air in middle ear. If the ossicular chain is, broken, conduction occurs in an alternate route of air, conduction. Air conduction is common in otosclerosis., Otosclerosis is the disease associated with fixation of, stapes to oval window., 3. Bone conduction, Bone conduction is the conduction of sound waves, through middle ear by bones. It occurs when middle, ear is affected. In this type of conduction, sound waves, are transmitted to cochlear fluid by the vibrations set, up in skull bones. Bone conduction is tested by placing, vibrating tuning forks or other vibrating bodies directly, on the skull. This route plays a role in transmission of, extremely loud sounds., ROLE OF EUSTACHIAN TUBE, Eustachian tube is not concerned with hearing, directly. However, it is responsible for equalizing the, pressure on either side of tympanic membrane.
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1018 Section 11 t Special Senses, , ROLE OF INNER EAR, TRAVELING WAVE, Movement of footplate of stapes against oval window, causes movement of perilymph in scala vestibuli. This, fluid does not move all the way from oval window to, round window through helicotrema. It immediately, hits the vestibular membrane near oval window. This, causes movement of fluid in scala media, since the, vestibular membrane is flexible., Movement of fluid in scala media causes bulging, of basal portion of basilar membrane towards scala, tympani (Fig. 174.1)., Bulging of basilar membrane increases the elastic, tension in basilar fibers in that portion of basilar, membrane. Elastic tension in basilar fibers initiates a, wave, which travels along basilar membrane towards, the helicotrema like that of arterial pulse wave. It is, called traveling wave., , FIGURE 174.1: Diagrammatic representation of cochlea., Arrows show displacement of fluid, , Resonance Point, Resonance point is the part of basilar membrane,, which is activated by traveling wave. In the beginning,, each traveling wave is weak (Fig. 174.2). While, traveling through basilar membrane from base towards, apex (helicotrema), the wave becomes stronger and, stronger and at one point (resonance point) of basilar, membrane, it becomes very strong and activates the, basilar membrane. This resonance point of basilar, membrane immediately vibrates back and forth. The, traveling wave stops here and does not travel further., Distance between stapes and resonance point is, inversely proportional to frequency of sound waves, reaching the ear. Traveling wave generated by highpitched sound disappears near the base of the cochlea., Wave generated by medium-pitched sound reaches, half of the way and the wave generated by low-pitched, sound travels the entire distance of basilar membrane., EXCITATION OF HAIR CELLS, Stereocilia of hair cells in organ of Corti are embedded, in tectorial membrane. Hair cells are tightly fixed by, cuticular lamina reticularis and the pillar cells or rods, of Corti., When traveling wave causes vibration of basilar, membrane at the resonance point, the basilar fiber,, rods of Corti, hair cells and lamina reticularis move, as a single unit. It causes movements of stereocilia, leading to excitement of hair cells and generation of, receptor potential., , FIGURE 174.2: Traveling waves for different frequencies, of sound, , ELECTRICAL EVENTS DURING PROCESS, OF HEARING, SOUND TRANSDUCTION, Sound transduction is a type of sensory transduction, (Chapter 139) in the hair cell (receptor cells) in organ, of Corti by which the sound energy is converted into, action potentials in the auditory nerve fiber., Electrical Events of Sound Transduction, Three types of electrical events that occur during, sound transduction are:, 1. Receptor potential or the cochlear microphonic, potential, 2. Endocochlear potential or endolymphatic potential, 3. Action potential in auditory nerve fiber.
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Chapter 174 t Mechanism of Hearing 1019, RECEPTOR POTENTIAL OR COCHLEAR, MICROPHONIC POTENTIAL, Receptor potential or cochlear microphonic potential, is the mild depolarization that is developed in the hair, cells of cochlea when sound waves are transmitted to, internal ear. Resting membrane potential in hair cells is, –60 mV. Sensory transduction mechanism in cochlear, receptor cells is different from the mechanism in other, sensory receptors., When sound waves reach internal ear traveling wave, is produced. It causes vibration of basilar membrane,, which moves stereocilia of hair cells away from modiolus, (towards kinocilium). It causes opening of mechanically gated potassium channels (Chapter 3) and influx of, potassium ions from endolymph, which contains large, amount of potassium ions. Influx of potassium ions, causes development of mild depolarization (receptor, potential) in hair cells up to –50 mV., Cochlear microphonic potential is non-propagative., But, it causes generation of action potential in auditory, nerve fiber. Due to depolarization hair cells release a, neurotransmitter, which generates action potential in, the auditory nerve fibers. Probable neurotransmitter, may be gulatamate., Movement of stereocilia away from modiolus (towards kinocilium) causes depolarization in hair cells., Movement of stereocilia in the opposite direction, (away from kinocilium) causes hyperpolarization., Ionic basis of hyperpolarization is not clearly known., It is suggested that calcium plays an important role, in this process. Hyperpolarization in hair cells stops, generation of action potential in auditory nerve fiber., , sharpness of sound. Hence, the outer hair cells are, collectively called cochlear amplifier. The electromotility, of hair cell is due to the presence of a contractile protein,, prestin (named after a musical notation presto)., Role of Efferent Nerve Fibers of Hair Cells, Efferent nerve fibers (Chapter 173) of hair cells also, play important role during sound transduction by, releasing acetylcholine., Efferent nerve fiber to inner hair cell terminates, on the auditory (afferent) nerve fiber where it leaves, the inner hair cell. It controls the generation of action, potential in auditory nerve fiber by inhibiting the release, of glutamate from inner hair cells., Efferent nerve fiber to outer hair cell terminates, directly on the cell body. It inhibits the electromotility, of this cell., ENDOCOCHLEAR POTENTIAL OR, ENDOLYMPHATIC POTENTIAL, Endocochlear or endolymphatic potential is the electrical potential developed in fluids outside the hair cells., Cochlear Fluids, Cochlear fluids are the extracellular fluids in the inner, ear. These fluids are perilymph and endolymph, which, have different composition., Perilymph, Scala vestibuli and scala tympani are filled with, perilymph, which is similar to ECF in composition with, high concentration of sodium ions., , ROLE OF HAIR CELLS, , Endolymph, , Inner hair cells and outer hair cells have different, roles during sound transduction., , Scala media is filled with endolymph, which contains, high concentration of potassium and low concentration of sodium. It is due to continuous secretion of, potassium ions by stria vascularis into scala media., , Role of Inner Hair Cells, Inner hair cells are responsible for sound transduction, i.e. these receptor cells are the primary sensory, cells, which cause the generation of action potential, in auditory nerve fibers., Role of Outer Hair Cells, Outer hair cells have a different action. These hair cells, are shortened during depolarization and elongated, during hyperpolarization. This process is called, electromotility or mechanoelectrical transduction. This, action of outer hair cells facilitates the movement of, basilar membrane and increases the amplitude and, , Electrical Potential, Difference in potassium concentration is responsible, for the development of an electrical potential difference, between endolymph and perilymph. Potential in, endolymph is positive up to +80 mV., Significance of Endocochlear Potential, Lower portion of the hair cells is bathed by perilymph., Head portion of hair cells penetrates the lamina reticularis and it is bathed by endolymph (Fig. 172.3)., Endolymph has a positive potential (+80 mV).
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1020 Section 11 t Special Senses, So inside the hair cells, the electrical potential is, –60 mV in comparison to that of perilymph and –140, mV in comparison to that of endolymph. High potential, difference sensitizes the hair cells so that, the excitability of hair cells increases. It also increases the response, of cells even to slight movement of stereocilia., ACTION POTENTIAL IN, AUDITORY NERVE FIBER, Action potential in auditory nerve fiber is generated by, cochlear microphonic potential. It obeys all-or-none, law and has a definite threshold and refractory period., Action potential to a click sound with moderate, intensity level consists of three successive spike, potentials called N1 N2 N3 representing synchronous, repetitive firing in many fibers., At high frequency, the synchronization of action, potential disappears and single spike occurs. Action, potential appears 0.5 to 1 millisecond after the, development of cochlear microphonic potential., , PROPERTIES OF SOUND, Sound has two basic properties:, 1. Pitch, which depends upon the frequency of sound, waves. Frequency of sound is expressed in hertz., Frequency of sound audible to human ear lies, between 20 and 20,000 Hz or cycles/second. The, range of greatest sensitivity lies between 2,000, and 3,000 Hz (cycles/second)., 2. Loudness or intensity, which depends upon the, amplitude of sound waves. It is expressed in, decibel (dB). The threshold intensity of sound, wave is not constant. It varies in accordance to, the frequency of sound., , APPRECIATION OF PITCH OF THE, SOUND – THEORIES OF HEARING, Many theories are postulated to explain the mechanism, by which the pitch of the sound is appreciated or the, frequency is analyzed. These theories are generally, classified into two groups. According to the first group,, the analysis of sound frequency is the function of cerebral, cortex and the cochlea merely transmits the sound., According to the second group of theories, the, frequency analysis is done by cochlea, which later, sends the information to cerebral cortex., THEORIES OF FIRST GROUP, 1. Telephone Theory of Rutherford, Telephone theory was postulated by Rutherford in 1880., It is also called frequency theory. According to this, , theory, the cochlea plays a simple role of a telephone, transmitter., , In telephone, sound vibrations are converted into, electrical impulses, which are transmitted by cables, to the receiving end. There the receiver instrument, converts the electrical impulses back into sound waves., Similarly, cochlea just converts the sound waves into, electrical impulses of same frequency. Impulses are, transmitted by auditory nerve fibers to cerebral cortex,, where perception and analysis of sound occur., It is believed that, the nerve fibers can transmit, maximum of 1,000 impulses per second. Thus, the, telephone theory fails to explain the transmission of, sound waves with frequency above 1,000 cycles per, second. So, a second theory was postulated., 2. Volley Theory, In 1949, Wever postulated this theory. Volley means, groups. According to this theory, the impulses of sound, waves with frequency above 1,000 cycles per second are, transmitted by different groups of nerve fibers. However,, this theory has no evidence to prove it. Thus, these two, theories were not accepted by many physiologists., THEORIES OF SECOND GROUP, 1. Resonance Theory of Helmholtz, Resonance theory was the first theory of hearing to, emerge in 1863. According to Helmholtz, analysis of, sound frequency is the function of cochlea. Basilar, membrane contains many basilar fibers. Helmholtz, named these basilar fibers resonators and compared, them with the resonators of piano., When a string in piano is struck, sound with a, particular note is produced. Similarly, when the sound, with a particular frequency is applied, the basilar, fibers in a particular portion of basilar membrane are, stimulated., Resonance theory was not accepted because the, individual resonators could not be identified in cochlea., Gradually, this theory was modified into another theory, called the place theory, which is more widely accepted., 2. Place Theory, According to this theory, nerve fibers from different, portions (places) of organ of Corti on basilar membrane give response to sounds of different frequency., Accordingly, corresponding nerve fiber from organ of, Corti gives information to the brain regarding the portion, of organ of Corti that is stimulated. Many experimental, evidences are available to support place theory.
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Chapter 174 t Mechanism of Hearing 1021, Experimental evidences supporting place theory, i. If a person is exposed to a loud noise of a particular frequency for a long period, he becomes, deaf for that frequency. It is found that the, specific portion of organ of Corti is destroyed as, in the case of boilermaker’s disease., ii. In experimental animals, destruction of a portion, of organ of Corti occurs by exposing the animal, to loud noise of a particular frequency, iii. In human high-tone deafness, there is degeneration of organ of Corti near the base of, cochlea or degeneration of nerve supplying, the cochlea near the base, iv. During exposure to high-frequency sound,, cochlear microphonic potentials show greater, voltage in hair cells near base of the cochlea., Also, during the exposure to low-frequency, sound, cochlear microphonic potentials show, greater voltage in hair cells near apex of the, cochlea., v. There is point-to-point representation of basilar, membrane in auditory cortex., 3. Traveling Wave Theory, From place theory, emerged yet another theory, called the traveling wave theory. This theory explains, how the traveling wave is generated in the basilar, , membrane. Development, generation, movement and, disappearance of traveling wave are already described, earlier in this chapter., , APPRECIATION OF LOUDNESS, OF SOUND, Appreciation of loudness of sound depends upon the, activities of auditory nerve fibers. Intensity or loudness, of sound correlates with two factors:, 1. Rate of discharge from the individual fibers of, auditory nerve, 2. Total number of nerve fibers discharging., When loudness of sound increases, it produces, large vibrations, which spread over longer area of, basilar membrane. This activates large number of hair, cells and recruits more number of auditory nerve fibers., So, the frequency of action potential is also increased., , LOCALIZATION OF SOUND, Sound localization is the ability to detect the source, from where sound is produced or the direction through, which sound wave is traveling. It is important for, survival and it helps to protect us from moving objects, such as vehicles., Cerebral cortex and medial geniculate body are, responsible for localization of sound.
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Chapter, , Auditory Defects, , 175, , TYPES AND CAUSES OF AUDITORY DEFECTS, , , , CONDUCTION DEAFNESS, NERVE DEAFNESS, , TESTS FOR HEARING, , , , , RINNE TEST, WEBER TEST, AUDIOMETRY, , TYPES AND CAUSES, OF AUDITORY DEFECTS, Auditory defects may be either partial or complete., Auditory defects are of two types:, 1. Conduction deafness, 2. Nerve deafness., CONDUCTION DEAFNESS, Conduction deafness is the type of deafness that, occurs due to impairment in transmission of sound, waves in the external ear or middle ear., Causes for Conduction Deafness, i. Obstruction of external auditory meatus with, dry wax or foreign bodies, ii. Thickening of tympanic membrane due to, repeated middle ear infection, iii. Perforation of tympanic membrane due to, inequality of pressure on either side, iv. Otitis media (inflammation of middle ear), v. Otosclerosis (fixation of footplate of stapes, against oval window) due to ankylosis., Ankylosis means the abnormal immobility and, consolidation of a joint., , NERVE DEAFNESS, Nerve deafness is the deafness caused by damage, of any structure in cochlea, such as hair cell, organ of, Corti, basilar membrane or cochlear duct or the lesion, in the auditory pathway., Causes for Nerve Deafness, i. Degeneration of hair cells due to some, antibiotics like streptomycin and gentamicin, ii. Damage of cochlea by prolonged exposure to, loud noise, iii. Tumor affecting VIII cranial nerve., , TESTS FOR HEARING, There are various tests to assess the sensation of, hearing. However, some simple tests called bedside, tests are usually carried before doing conventional, types of hearing tests. Such simple tests are useful to, know whether the hearing is normal or less., Bedside tests:, 1. Whispering test, 2. Tickling of watch test.
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Chapter 175 t Auditory Defects 1023, Whispering Test, The examiner stands about 60 cm away from the, subject at his side and whispers some words. If the, subject is not able to hear the whisper, then hearing, deficit is suspected., Tickling of Watch Test, Wrist watch with tickling sound is kept near the ear of, the subject. The subject suffering from hearing defects, cannot hear the tickling sound of watch., Routine Tests for Hearing, Routine tests for hearing are of three types:, 1. Rinne test, 2. Weber test, 3. Audiometry., First two tests are done by using a tuning fork with, high frequency. Mostly, a tuning fork with 512 cycles per, second is used. By turning fork tests, only the nature of, auditory defect is determined. By audiometry, both nature, and severity of auditory defects can be determined., RINNE TEST, Base of a vibrating tuning fork is placed on mastoid, process, until the subject cannot feel the vibration and, cannot hear the sound. When the subject does not hear, the sound any more, the tuning fork is held in air in front, of the ear of same side. Normal person hears vibration, in air even after the bone conduction ceases because, in, normal conditions, air conduction via ossicles is better, than bone conduction. But in conduction deafness, the, vibrations in air are not heard after cessation of bone, conduction. Thus in conduction deafness, the bone, conduction is better than air conduction., In nerve deafness, both air conduction and bone, conduction are diminished or lost., WEBER TEST, Base of a vibrating tuning fork is placed on the vertex, of skull or the middle of forehead. Normal person hears, the sound equally on both sides. In unilateral conduction, deafness (deafness in one ear), the sound is heard, louder in diseased ear. In unaffected ear, there is a mask, ing effect of environmental noise. So, the sound through, bone conduction is not heard as clearly as on the affected, side. In affected side, the sound is louder due to the, absence of masking effect of environmental noise., During unilateral nerve deafness, sound is heard, louder in the normal ear., , FIGURE 175.1: Audiogram in a patient with, conductive deafness, , AUDIOMETRY, Audiometry is the technique used to determine the nature, and the severity of auditory defect. An instrument called, audiometer is used. This instrument is an electronic, function generator or oscillator, connected to an ear, phone. This instrument is capable of generating sound, waves of different frequencies from lowest to highest., Intensity (loudness or volume) of sound at each, frequency is adjusted on the basis of previous studies in, normal persons., Thus, before calibrating the instrument, minimum, (threshold) volume or intensity or loudness, for each, frequency of sound heard by normal persons is, determined. Minimum intensity is set in the instrument, as zero. Now, while testing the patient, the loudness, is increased above zero level (Fig. 175.1). Intensity of, sound is expressed in decibel (dB)., At a particular frequency, if the patient hears the, sound with loudness of 30 dB above zero level, the, person is said to have hearing loss of 30 dB for that, particular frequency. During the tests by audiometer,, the subject’s ability to hear the sounds with 8 to 10, different frequencies is observed and the hearing loss is, determined for each frequency. By using these values,, the audiogram is plotted., Audiometer has an electronic vibrator also. It is, used to test the bone conduction from mastoid process, into the cochlea.
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Chapter, , Sensation of Taste, , , , , , , , , 176, , TASTE BUDS, PATHWAY FOR TASTE, PRIMARY TASTE SENSATIONS, DISCRIMINATION OF DIFFERENT TASTE SENSATIONS, TASTE SENSATIONS AND CHEMICAL CONSTITUTIONS, TASTE TRANSDUCTION, APPLIED PHYSIOLOGY – ABNORMALITIES OF TASTE SENSATION, , TASTE BUDS, , 3. Circumvallate Papillae, , Sense organs for taste or gustatory sensation are, the taste buds. Taste buds are ovoid bodies with a, diameter of 50 µ to 70 µ. In adults, about 10,000 taste, buds are present and the number is more in children., In old age, many taste buds degenerate and the taste, sensitivity decreases., , Circumvallate papillae are large structures present on, the posterior part of tongue and are many in number., These papillae are arranged in the shape of ‘V’. Each, papilla contains many taste buds (up to 100)., , SITUATION OF TASTE BUDS, , Taste bud is a bundle of taste receptor cells, with, supporting cells embedded in the epithelial covering, of the papillae (Fig. 176.1). Each taste bud contains, about 40 cells, which are the modified epithelial cells., Cells of taste bud are divided into four groups:, , Most of the taste buds are present on the papillae of, tongue. Taste buds are also situated in the mucosa, of epiglottis, palate, pharynx and the proximal part of, esophagus., Types of papillae located on tongue:, 1. Filiform papillae, 2. Fungiform papillae, 3. Circumvallate papillae., 1. Filiform Papillae, Filiform papillae are small and conical-shaped, papillae, situated over the dorsum of tongue. These, papillae contain less number of taste buds (only a few)., 2. Fungiform Papillae, Fungiform papillae are round in shape and are situated, over the anterior surface of tongue near the tip., Numerous fungiform papillae are present. Each papilla, contains moderate number of taste buds (up to 10)., , STRUCTURE OF TASTE BUD, , Type of Cells in Taste Bud, 1., 2., 3., 4., , Type I cells or sustentacular cells, Type II cells, Type III cells, Type IV cells or basal cells., Type I cells and type IV cells are supporting cells., Type III cells are the taste receptor cells. Function, of type II cell is unknown. Type I, II and III cells have, microvilli, which project into an opening in epithelium, covering the tongue. This opening is called taste pore., Neck of each cell is attached to the neck of other. All, the cells of taste bud are surrounded by epithelial cells., There are tight junctions between epithelial cells and, the neck portion of the type I, II and III cells, so that only, the tip of these cells are exposed to fluid in oral cavity.
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Chapter 176 t Sensation of Taste 1025, SECOND ORDER NEURON, Second order neurons are in the nucleus of tractus, solitarius. Axons of second order neurons run through, medial lemniscus and terminate in posteroventral, nucleus of thalamus., THIRD ORDER NEURON, Third order neurons are in the posteroventral nucleus, of thalamus. Axons from third order neurons project, into parietal lobe of the cerebral cortex., TASTE CENTER, Center for taste sensation is in opercular insular cortex,, i.e. in the lower part of postcentral gyrus, which receives, cutaneous sensations from face. Thus, the taste fibers, do not have an independent cortical projection., , PRIMARY TASTE SENSATIONS, FIGURE 176.1: Taste bud, , Cells of taste buds undergo constant cycle of growth,, apoptosis and regeneration., , Primary or fundamental taste sensations are divided, into five types:, 1. Sweet, 2. Salt, , PATHWAY FOR TASTE, RECEPTORS, Receptors for taste sensation are the type III cells of, taste buds. Each taste bud is innervated by about 50, sensory nerve fibers and each nerve fiber supplies at, least five taste buds through its terminals., FIRST ORDER NEURON, First order neurons of taste pathway are in the nuclei, of three different cranial nerves, situated in medulla, oblongata. Dendrites of the neurons are distributed to, the taste buds. After arising from taste buds, the fibers, reach the cranial nerve nuclei by running along the, following nerves (Fig. 176.2):, 1. Chorda tympani fibers of facial nerve, which run, from anterior two third of tongue, 2. Glossopharyngeal nerve fibers, which run from, posterior one third of the tongue, 3. Vagal fibers, which run from taste buds in other, regions., Axons from first order neurons in the nuclei of these, nerves run together in medulla oblongata and terminate, in the nucleus of tractus solitarius., , FIGURE 176.2: Pathway for taste sensation
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1026 Section 11 t Special Senses, 3. Sour, 4. Bitter, 5. Umami., Man can perceive more than 100 different tastes., Other taste sensations are just the combination of two, or more primary taste sensations., Combination of Taste Sensation, with Other Sensations, Sometimes, taste sensation combines with other sensations to give rise to a different sensation. For example,, combination of taste, smell and touch senses, gives, rise to sensation of flavor. Combination of taste with, pain gives rise to sensation of ginger., , DISCRIMINATION OF DIFFERENT, TASTE SENSATIONS, Earlier, it was believed that different areas of tongue, were specialized for different taste sensation. Now it, is clear that all areas of tongue give response to all, types of taste sensations. Usually, in low concentration of taste substance, each taste bud gives response, to one primary taste stimulus. However, in high, concentration, the taste buds give response to more, than one type of taste stimuli., It is also clear now that each afferent nerve fiber from, the taste buds carry impulses of one taste sensation., , TASTE SENSATIONS AND, CHEMICAL CONSTITUTIONS, Substances causing sour or salt tastes are mostly, electrolytes. Bitter and sweet tastes are caused by, electrolytes or non-electrolytes., SWEET TASTE, Sweet taste is produced mainly by organic substances, like monosaccharides, polysaccharides, glycerol,, alcohol, aldehydes, ketones and chloroform. Inorganic, substances, which produce sweet taste are lead and, beryllium., SALT TASTE, Salt taste is produced by chlorides of sodium,, potassium and ammonium, nitrates of sodium and, potassium. Some sulfates, bromides and iodides also, produce salt taste., , SOUR TASTE, Sour taste is produced because of hydrogen ions in, acids and acid salts., BITTER TASTE, Bitter taste is produced by organic substances like, quinine, strychnine, morphine, glucosides, picric acid, and bile salts and inorganic substances like salts of, calcium, magnesium and ammonium. Bitterness of the, salts is mainly due to cations., UMAMI, Umami is the recently recognized taste sensation., Umami is a Japanese word, meaning ‘delicious’., Receptors of this taste sensation respond to glutamate,, particularly monosodium glutamate (MSG), which is, a common ingredient in Asian food. However, excess, MSG consumption is proved to produce Chinese, restaurant syndrome in some people taking Chinese, food regularly. Common symptoms are headache,, flushing, sweating, perioral numbness, chest pain., In severe conditions, airway swelling and obstruction, and cardiac arrhythmia occur., Threshold for Taste Sensations, Sweet taste Sugar, : 1 in 200 dilution, Salt taste, Sodium chloride : 1 in 400 dilution, Sour taste Hydrochloric acid : 1 in 15,000 dilution, Bitter taste Quinine, : 1 in 2,000,000 dilution., Bitter taste has very low threshold and sweet, taste has a high threshold. Threshold for umani is not, known., , TASTE TRANSDUCTION, Taste transduction is the process by which taste, receptor converts chemical energy into action potentials, in the taste nerve fiber. Receptors of taste sensation are, chemoreceptors, which are stimulated by substances, dissolved in mouth by saliva. The dissolved substances, act on microvilli of taste receptors exposed in the taste, pore. It causes the development of receptor potential, in the receptor cells. This in turn, is responsible for the, generation of action potential in the sensory neurons., Taste Receptor, Generally, taste receptor is a G-protein coupled, receptor (GPCR). It is also called G protein gustducin.
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Chapter 176 t Sensation of Taste 1027, However, several other receptors are also involved in, taste sensation. Transduction mechanism is different in, each taste receptor cells., SWEET RECEPTOR, Receptor for sweet taste is GPCR. The sweet, substances bind to receptor and cause depolarization, via cyclic AMP., SALT RECEPTOR, Receptor for salt taste is called epithelial sodium, channel (ENaC). It acts like ENaC receptors in other, parts of the body. When sodium enters, this receptor, releases glutamate, which causes depolarization., SOUR RECEPTOR, Sour sensation also has the same ENaC receptor., The proton (hydrogen) enters the receptor and causes, depolarization. It is believed that besides ENaC, other, receptors such as hyperpolarization-activated cyclic, nucleotide-gated cation channel (HCN) also are, involved in sour sensation., BITTER RECEPTOR, Bitter receptor is a GPCR. In bitter receptor, the sour, substances activate phospholipase C through G, proteins. It causes production of inositol triphosphate, (IP3), which initiates depolarization by releasing, calcium ions., , is intensified by the presence of guanosine monophosphate (GMP) and inosine monophosphate (IMP)., , APPLIED PHYSIOLOGY –, ABNORMALITIES OF TASTE SENSATION, AGEUSIA, Loss of taste sensation is called ageusia. Taste buds, in anterior two thirds of the tongue are innervated by, the chorda tympani branch of facial nerve. Chorda, tympani nerve receives taste fibers from tongue via, lingual branch of mandibular division of trigeminal, nerve. So, the lesion in facial nerve, chorda tympani or, mandibular division of trigeminal nerve causes loss of, taste sensation in the anterior two third of the tongue., Lesion in glossopharyngeal nerve leads to loss of, taste in the posterior one third of the tongue., Temporary loss of taste sensation occurs due, to the drugs like captopril and penicillamine, which, contain sulfhydryl group of substances., HYPOGEUSIA, Hypoguesia is the decrease in taste sensation. It is due, to increase in threshold for different taste sensations., However, the taste sensation is not completely lost., TASTE BLINDNESS, Taste blindness is a rare genetic disorder in which the, ability to recognize substances by taste is lost., DYSGEUSIA, , UMAMI RECEPTOR, Umami receptor is called metabotropic glutamate, receptor (mGluR4). Glutamate causes depolarization of, this receptor. Exact mechanism of depolarization is not, clearly understood. Activation of umami taste receptor, , Disturbance in the taste sensation is called dysgeusia. It is found in temporal lobe syndrome, particularly, when the anterior region of temporal lobe is affected., In this condition, the paroxysmal hallucinations of, taste and smell occur, which are usually unpleasant.
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Chapter, , Sensation of Smell, , 177, , OLFACTORY RECEPTORS, VOMERONASAL ORGAN, , , , , , , , , , VOMERONASAL ORGAN IN HUMAN BEINGS, , OLFACTORY PATHWAY, OLFACTORY TRANSDUCTION, CLASSIFICATION OF ODOR, THRESHOLD FOR OLFACTORY SENSATION, ADAPTATION, APPLIED PHYSIOLOGY – ABNORMALITIES OF OLFACTORY SENSATION, , , , , ANOSMIA, HYPOSMIA, HYPEROSMIA, , OLFACTORY RECEPTORS, Olfactory receptors are situated in olfactory mucus, membrane, which is the modified mucus membrane, that lines upper part of nostril. Olfactory mucus, membrane consists of 10 to 20 millions of olfactory, receptor cells supported by the sustentacular cells., Mucosa also contains mucus-secreting Bowman, glands (Fig. 177.1)., Olfactory receptor cell is a bipolar neuron. Dendrite, of this neuron is short and it has an expanded end, called olfactory rod. From olfactory rod, about 10 to 12, cilia arise. Cilia are non-myelinated, with a length of, 2 µ and a diameter of 0.1 µ. These cilia project to the, surface of olfactory mucus membrane., Mucus secreted by Bowman glands continuously, lines the olfactory mucosa. Mucus contains some, proteins, which increase the actions of odoriferous, substances on receptor cells., , VOMERONASAL ORGAN, Vomeronasal organ is an accessory olfactory organ, found in many animals including mammals. This, organ was discovered in 1813, by a Danish physician, , Ludwig Jacobson, hence it is also called Jacobson, organ. It is enclosed in a cartilaginous capsule, which, , opens into the base of nasal cavity. Olfactory receptors, of this organ are sensitive to non-volatile substances, such as scents and pheromones. Vomeronasal organ, helps the animals to detect even the trace quantities of, chemicals. Impulses from this organ are sent to amygdala and hypothalamus via accessory olfactory bulb., VOMERONASAL ORGAN IN HUMAN BEINGS, In human beings, the vomeronasal organ was considered as vestigial or non-functional. Recently, it is found, that this organ is present in the form of vomeronasal, pits on the anterior part of nasal septum. Receptors of, vomeronasal pit detect odorless human pheromones or, vomeropherins, at a very low concentration in air. Refer, Chapter 62 for details of pheromones. The subconscious detection of odorless chemical messengers in, air is considered as the sixth sense in human beings., , OLFACTORY PATHWAY, Axons of bipolar olfactory receptors pierce the, cribriform plate of ethmoid bone and reach the
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Chapter 177 t Sensation of Smell 1029, , FIGURE 177.1: Olfactory mucus membrane and pathway for olfactory sensation, , olfactory bulb. Here, the axons synapse with dendrites, of mitral cells. Different groups of these synapses, form globular structures called olfactory glomeruli., , Axons of mitral cells leave the olfactory bulb and, form olfactory tract. Olfactory tract runs backward and, ends in olfactory cortex, through the intermediate and, lateral olfactory stria., Olfactory cortex includes the structures, which, form a part of limbic system. These structures, are anterior olfactory nucleus, prepyriform cortex,, olfactory tubercle and amygdala., , OLFACTORY TRANSDUCTION, Olfactory transduction is the process by which, olfactory receptor converts chemical energy into, action potentials in olfactory nerve fiber. The, odoriferous substance stimulates the olfactory, receptors, only if it dissolves in mucus, covering the, olfactory mucus membrane. Molecules of dissolved, substance, bind with receptor proteins in the cilia, and form substance-receptor complex. Substancereceptor complex activates adenyl cyclase that, causes the formation of cyclic AMP. Cyclic AMP in, turn, causes opening of sodium channels, leading to, influx of sodium and generation of receptor potential., Receptor potential causes generation of action, potential in the axon of bipolar neuron., , CLASSIFICATION OF ODOR, Odor is classified into various types. Substances, producing different types of odor are:, 1. Aromatic or resinous odor: Camphor, lavender,, clove and bitter almonds, 2. Ambrosial odor: Musk, 3. Burning odor: Burning feathers, tobacco, roasted, coffee and meat, 4. Ethereal odor: Fruits, ethers and beeswax, 5. Fragrant or balsamic odor: Flowers and perfumes, 6. Garlic odor: Garlic, onion and sulfur, 7. Goat odor: Caproic acid and sweet cheese, 8. Nauseating odor: Decayed vegetables and feces, 9. Repulsive odor: Bed bug., , THRESHOLD FOR, OLFACTORY SENSATION, Ethyl ether, : 5.8 mg/L of air, Chloroform, : 3.3 mg/L of air, Peppermint oil, : 0.02 mg/L of air, Butyric acid, : 0.009 mg/L of air, Artificial musk, : 0.00004 mg/L of air, Methyl mercaptan : 0.0000004 mg/L of air., Thus, methyl mercaptan produces olfactory, sensation even at a low concentration of 0.0000004, mg/L of air.
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1030 Section 11 t Special Senses, , ADAPTATION, Olfactory receptors are phasic receptors and adapt, very rapidly. Within one second, the adaptation occurs, up to 50%., , APPLIED PHYSIOLOGY – ABNORMALITIES, OF OLFACTORY SENSATION, ANOSMIA, Anosmia refers to total loss of sensation of smell,, i.e. inability to recognize or detect any odor. It may, be temporary or permanent. Temporary anosmia, is due to obstruction of nose, which occurs during, common cold, nasal sinus and allergic conditions., , Permanent anosmia occurs during lesion in olfactory, , tract, meningitis and degenerative conditions such as, Parkinson disease and Alzheimer disease., HYPOSMIA, Hyposmia is the reduced ability to recognize and to, detect any odor. The odors can be detected only at, higher concentrations. It is the most common disorder of, smell. Hyposmia also may be temporary or permanent., It occurs due to same causes of anosmia., HYPEROSMIA, Hyperosmia is the increased or exaggerated olfactory, sensation. It is also called olfactory hyperesthesia. It, occurs in brain injury, epilepsy and neurotic conditions.
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Questions in Special Senses 1031, , QUESTIONS IN SPECIAL SENSES, , LONG QUESTIONS, 1. Draw a diagram of visual pathway and explain it., Indicate the effects of lesions at different levels of, optic pathway., 2. Give an account of accommodation. Add a note, on presbyopia., 3. Explain the auditory pathway with suitable, diagram. Add a note on auditory defects., 4. Explain the mechanism of hearing., 5. What is sound transduction? Explain the electrical, events, which occur during sound transduction, 6. Describe how the pitch of the sound is analyzed, in human ear (theories of hearing)., , SHORT QUESTIONS, 1., 2., 3., 4., 5., 6., 7., 8., 9., 10., 11., 12., 13., 14., , Retina., Ocular muscles., Ocular movements., Visual receptors., Aqueous humor., Intraocular pressure., Glaucoma., Fundus oculi., Lens of eye., Cataract., Lacrimal glands., Rhodopsin., Phototransduction., Dark adaptation., , 15., 16., 17., 18., 19., 20., 21., 22., 23., 24., 25., 26., 27., 28., 29., 30., 31., 32., 33., 34., 35., 36., 37., 38., 39., 40., 41., 42., 43., , Light adaptation., Nyctalopia., ERG., Diplopia., Hemianopia., Effects of lesion in optic pathway., Accommodation reflex., Presbyopia., Theories of color vision., Color blindness., Errors of refraction., Auditory ossicles., Tympanic reflex., Cochlea., Organ of Corti., Role of middle ear in hearing (Functions of, middle ear)., Role of inner ear in hearing (Functions of, internal ear)., Impedance matching., Traveling wave., Electrical potentials in cochlea., Theories of hearing., Auditory defects., Tests for hearing., Audiometry., Taste buds., Taste transduction., Taste pathway., Olfactory transduction., Olfactory pathway.
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Index, Page numbers followed by f for figure and t for table, respectively., , A, A band 171, Abdominal belts 741, Abducent nerve 973, Abnormal, apoptosis 18, gastric emptying 275, heart sound 549, hemoglobin 78, derivatives 79, menstruation 490, 491, pacemaker 569, plantar reflex 799, pulse 625, in aortic regurgitation 626, in patent ductus arteriosus 626, rhythm of heart 547, sperms 496, V wave 628, venous pulse 628, X wave 628, Y wave 628, Abnormalities of, micturition 344, ovary 496, sodium-potassium pump 37, taste sensation 1027, uterus 496, waves in jugular pulse tracing 628, ABO, agglutinogens and agglutinins 141, blood groups 139, group 142t, determination of 140, in blood transfusion 141, system 140, Abortion 448, Abrupt, apnea, causes of 732, hyperpnea, causes of 732, Absolute refractory period 186, 531,, 769, Absorption from gastrointestinal tract, 406, Absorption of, calcium 406, , carbohydrates 264, 288, cerebrospinal fluid 950, fats 253, 264, fructose 288, galactose 288, glucose 288, iron 82, lipids 293, minerals 264, proteins 264, 291, vitamins 264, water 264, Absorptive function 6, 255, 264, 267,, 355, Abuse of anabolic steroids 464, Abuses of diuretics 348, Accelerated hypertension 614, Accelerative force 740, Accessory, digestive organs 220, expiratory muscles 683, inspiratory muscles 683, olfactory organ 1028, sex organs 455, 463, 473, 474, in males 466, spleens 153, Accidental hemorrhage 651, Acclimatization 739, Accommodation 995, of stomach 274, reflex 799, 997, 997f, Acetone breathing 423, Acetylcholine 202f, 449, 606, 607, 666,, 789, 958, action of 201, 449, destruction of 202, 449, receptors 790, Acetylcholinesterase 449, Achalasia cardia 273, Achlorhydria 240, Achromatic interval 980, Achromatopsia 1002, Acid-base balance 42, by acid-base buffer system,, regulation of 43, by renal mechanism, regulation, of 45, , by respiratory mechanism, regulation, of 45, regulation of 43, 45f, 60, 676, Acid-base disturbance 46t, Acid-base status, determination of 43, Acidification of urine 330, 331, Acidophilic cells 376, Acidosis 45, 338, 421, 423, 428, causes of 46t, Acini 224, 241, and duct system in salivary glands, 225f, Acne 356, Acquired, color blindness, causes for 1002, immune deficiency diseases 118, immunity or specific immunity 107, Acromegalic gigantism 384, Acromegalic hand 385f, Acromegaly 379, 384, 385f, Acromicria 386, Acrosome 471, Actin 123, filaments 172, molecule 173, Acting on genes 374, Actinin 173, Action in males 384, Action of, acetylcholine 201, and catecholamines 313f, cholecystokinin 247, erythropoietin 445, estrogen 479, GABA 783, GH–somatomedin 379, glucagon 419, insulin 417, leptin 450, 860, oxytocin 384, on mammary glands 382, pancreatic polypeptide 420, parathormone 402, pepsin 232, progesterone 481, prostaglandins 446, 448, protein hormones 373f
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1034 Essentials of Medical Physiology, secretin 246, somatomedin C 379, somatostatin 420, steroid hormones 374f, sympathetic nerves 591, testosterone 464, thrombopoietin 445, thyroid hormones 393, TSH 394, vagus nerve 590, Action potential 190, 206, 525, 528, curve 190, in auditory nerve fiber 1020, in nerve fiber 767f, in skeletal muscle 191f, in ventricular muscle 526f, or nerve impulse 766, properties of 190, 767, with plateau 206, 207, Actions of, acetylcholine 449, adrenal 433, adrenaline 440, angiotensin II 609, angiotensin III 610, angiotensin IV 610, angiotensins 310, antibodies 114, calcitonin 405, camp 373, carboxypeptidases 243, chymotrypsin 243, cytotoxic T cells 111, enzymes of gastric juice 233, erythropoietin 75, FSH 380, gastrin on gastric secretion 237, glucagon 418, growth hormone 377, HCG 506, heart 522, regulation of 523, heparin 450, histamine 450, insulin 415, kallikreins 451, kinins 451, leptin 450, LH 380, melatonin 444, neuromodulators 792, noradrenaline 440, pancreatic polypeptide 420, parasympathetic 955t, parathormone 400, , placental, estrogen 506, progesterone 506, renin 445, serotonin 450, somatostatin 420, sympathetic 955t, blocking agents 959t, thyroid-stimulating hormone 394, trypsin 243, Activation of, apoptosis 17, vitamin D 401, Activators of platelets 125, Active, artificial immunization 118, electrode 553, immunization 117, natural immunization 117, reabsorption 320, tension 185, transport 31, transport mechanism 949, transport vs facilitated diffusion 31, Activin 458, 461, Activity of, cellular enzymes 392, gastrointestinal tract 638, gland, regulation of 370, mitochondria 391, Actomyosin complex 194, 195, Acuity of vision 985, Acute, adrenal insufficiency 437, gastritis, causes of 239, heart failure 662, 663, hemorrhage 90, 652, 659, myocardial ischemia 556, pain 838, pancreatitis 247, renal failure 334, 337, causes 337, 338, Adaptation of, receptors in semicircular canal 925, sensory 777, Addison’s, anemia 93, disease 437, Addisonian crisis 437, Additional respiratory center 719, Adenosine 317, 631, diphosphate 128, triphosphate 31, ADH mechanism 655, 860, Adherens junctions 25, 521, Adhesiveness 124, Adiadochokinesis 877, , Adipocytes 295, Adipose tissue 295, Adiposogenital syndrome 466, Adjustment of tone 913, Adolph fick 577, Adrenal, actions 433, cortex 425, 461, 465, 502, control of 857, crisis 437, gland 425f, functional anatomy of 425, importance of 425, insufficiency, chronic 437, medulla 425, 439, control of 857, origin of Cushing syndrome 435, sex hormones 433, virilism 436, Adrenaline 610, actions of 440, apnea 724, Adrenergic, alpha blockers 615, beta blockers 615, nerve fibers 765, receptors 440, 441t, Adrenocorticotropic hormone 380, 793, Adrenogenital syndrome 436, causes of 436, Adults 62, 71, 464, respiratory distress syndrome 685, rickets 414, stem cells 21, Aerobic, exercises 665, glycolysis 198, Aerobic metabolism 665, Afferent arteriole 312, Afferent arteriole, constriction of 318, Afferent connections 869, 871, 873,, 873f, of corpus striatum 879f, of red nucleus 846f, of reticular formation 902f, to hypothalamus 856, After, discharge 801, hyperpolarization 191, image 1001, load 184, meals 69, puberty 466, Ageusia 1027, Agglutination 114, 124, 140, Agglutination occurs with, antiserum A 140
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Index 1035, antiserum B 140, both antisera A and B 140, Agglutination of, latex particles 509, RBCs 137, Agglutinogen 139, Aggregation 124, Aging effects on dehydration 56, Agranular cells 309, Agranulocytes 97, Agranulocytosis 99, Air, conduction 1017, embolism 147, Airway resistance 688, Akinesia 882, Albinism 353, Albumin 391, 462, ratio 61, Albuminuria 334, Alcoholic intoxication 728, Alcoholism 1002, Aldosterone 610, antagonists 349, escape 427, 427f, importance of 428, Alertness reactions 851, Alkalemia 728, Alkaline urine 728, Alkalosis 45, 428, causes of 47t, Allergens 109, 120, Allergic, reactivity 110, responses 449, Allergy 120, Allocortex 886, Allogeneic or heterologous blood, transfusion 147, All-or-none law 530, 769, and staircase phenomenon in, cardiac muscle 530f, Alpha, adrenergic receptors 441, adrenoceptor blockers 615, and beta receptors 441, block 930, cells 376, glucosidase inhibitors 424, granules 123, motor neurons 806, 833, receptors 441, 442, rhythm 929, waves 932, Alternate pathway 114, Alveolar air 703, 703t, , definition of 703, vs inspired air 703, Alveolar cells 675, or pneumocytes 675, Alveolar, ducts 675, epithelial cells 684, fluid and surfactant 675, hyperplasia 380, membrane 675, sac 675, ventilation 700, definition of 700, Alveoli 224, 241, 675, 708t, 709f, atmospheric air, diffusion of carbon, dioxide from 708, blood, diffusion of oxygen from 708, Alveolus 675, to pulmonary capillary, diffusion of, oxygen from 707f, Alzheimer’s disease 18, 21, 763, Ameboid movement 101, Amenorrhea 393, 491, Ametropia 1004, Ametropic eye 1004, Amine precursor 281, Amines 788, Amino acids 252, 788, of polypeptide chains of globin 78t, reabsorption of 323, Aminopeptidases 291, Aminophospholipids 5, Ammonia mechanism 332, Ammonium 332, Amnesia 936, Amplitude of, accommodation 998, at different ages 998, QRS complex 560, Ampulla 456, 920, of vater 241, 250, Amygdala and appetite center 236, Amylolytic enzyme in pancreatic juice, 287, Amylolytic enzymes 262, 287, Amylolytic enzymes in succus entericus, 287, Anabolic steroids 464, Anabolic steroids, abuse of 464, Anabolic-androgenic steroids 464, Anacrotic, limb 623, pulse 625, Anaerobic, exercises 665, metabolism 665, Analgesia 810, 843, , system 840, Analgesic pathway 841, 841f, Anaphylactic, reactions 661, shock 661, Anatomical, dead space 701, divisions 864, of cerebellum 864, shunt 641, synapses 781f, Anchoring junctions 24, 24f, Androgen-binding protein 458, Androgenic actions 461, Androgens 433, 461, Androsterone 462, Anelectrotonic potentials 766, Anemia 70, 89, 93, 150, 338, 733, classification of 89, of chronic diseases 93, Anemic hypoxia 727, causes for 727, Anerobic glycolysis 198, Anesthesia 852, Angina pectoris 633, treatment for 633, Angiotensin I 310, Angiotensin II, actions of 609, Angiotensin III, actions of 610, Angiotensin IV, actions of 610, Angiotensinases 310, Angiotensin-converting enzyme 310,, 609f, Angiotensinogen or renin substrate 310, Angiotensins 610, actions of 310, Angle of anterior chamber 968, Animal milk, disadvantages of 512, Animals 247, 264, Anisocytes 70, Anisometropia 1005, Ankle clonus 799, Ankylosis 1022, Anopia 991, Anorexia 240, Anosmia 862, 1030, Anosognosia 852, Anovulatory cycle 491, Ansiform lobe 864, Antagonists 615, Anterior, chamber, angle of 968, coronary veins 630, corticospinal tract 817, curvature 995, epithelium 972, limb 853, 854
Page 1057 :
1036 Essentials of Medical Physiology, of internal capsule 853, lobe of cerebellum 864, median fissure 804, or ventral, funiculus 806, white column 806, perforated substance 991, pituitary 502, control of 857, hormones 488, or adenohypophysis 376, secretion, regulation of 376, spinocerebellar tract 810, spinothalamic tract 807, vestibulospinal tract 818, white, column 820, commissure 806, Anterolateral sulcus 804, Anti-allergic actions 432, Antiarrhythmic drugs 564, Antibodies 113, actions of 114, against hCG 509, direct actions of 114, or immunoglobulins 113, Anticlotting mechanism in body 133, Anticoagulant function 676, Anticodon 16, Antidiabetogenic hormone 421, Antidiuretic effect 382, cause 610, Antidiuretic hormone 40f, 382, 857, Antidromic or axon reflex 607, 647, Antidromic vasodilator fibers 607, 647, Anti-G suit 741, Antigen, and antibody in ABO blood groups, 140t, presentation 111f, 112, presenting cells 110, Antigens 108, Antigravity reflexes 796, Antihypertensive drugs 615, Anti-inflammatory effects 431, Anti-insulin action 430, Anti-insulin hormones 421, Antimicrobial peptides 262, Antiperistalsis 276, Antiperistaltic contractions 498, Antiport 31, 322, pump 31, Antiseptic action 255, Antisera A and B, agglutination occurs, with 140, Antiserum A, agglutination occurs with, 140, Antiserum from rabbit 509, , Antithyroid substances 398, Antrum 230, Anuria 337, Anvil 1008, Anxiety complexes 393, Aorta 524, coarctation of 550, Aortic, area 548, coronary artery bypass graft 633, nerve 593, pressure 540, changes cardiac cycle 540, curve 540, reflex 592, regurgitation 626f, valve 522, Apex beat area 548, Aphasia 894, Apical margins 22, Aplastic anemia 93, Apnea 719, 723-725, adrenaline 724, after hyperventilation 724, classification of 724, time 724, Apneic period 731, Apneustic center 717, Apocrine glands 357, control of 358, Apocrine sweat glands 357t, Aponeurosis 169, Apoproteins 294, Apoptosis 11, 17, abnormal 18, activation of 17, inhibiting factor 18, Apoptotic process 18, Apotransferrin 82, Appearance of, gong sound 613, heart sounds in phonocardiogram, 548, muffled sound 613, tapping sound, first phase 613, Appendages of skin 353, Appendicitis 269, Apud cells 281, Aquaporins 382, Aqueductus sylvius 950, Aqueous humor 971, 972, drainage of 972, properties of 971, Arachidonic acid 447, Archicerebellum 865, 869, Archicortex 898, Archicortical structures 898, Architecture of cutaneous blood vessels, , 646, Arcuate artery 312, Area for equilibrium 894, Area of, blood vessels 599, continuous blood flow 681, intermittent flow 681, zero blood flow 680, Areas and connections of, frontal lobe 892t, occipital lobe 895t, parietal lobe 894t, temporal lobe 894t, Areas of, somesthetic area 892, vasomotor center 588, visual cortex 895, 991, Argentaffin cells 261, Arginine 418, Argyll robertson pupil 998, Aromatase 458, activity 380, 488, Arrector pili 206, 353, Arrhythmia 562, classification of 562, 565f, definition of 562, Arterial blood 46t, Arterial blood pressure 393, 602, direct method to 612, regulation of 605, Arterial, cannula 582, pulse 622, system 523, Arteries 524, 629, Arteriography 581, Arterioles 524, dilatation of 647, Arteriosclerosis 396, 524, Artery, pulmonary 583f, Artificial, kidney 346, pacemaker 569, resistance 582, respiration 749, manual methods of 749, valve 580, Ascending, limb 307, of henle loop 349, posterior column tracts 813, reticular activating system 903, 934, reticular formation 903f, tracts of spinal cord 807, 808t, Aschheim-Zondek test 508, Aspermia 472, Asphyxia 730, Asplenia 154
Page 1058 :
Index 1037, Association, fibers 868, tracts 807, Astasia 877, Astereognosis 852, Asthenia 423, 877, Astigmatism 1005, cause of 1005, Astrocytes 773, Asynchronous closure 545, Asynergia 877, Ataxia 852, 877, Atelectasis 734, causes of 734, Atherosclerosis 295, 297, 392, 396,, 495, 524, 564, Atherosclerotic plaque 632, Athetoid hand 852, Athetosis 852, 883, Atlas 804, Atmospheric, air alveoli, diffusion of oxygen from, 707, temperature 148, Atonia 876, Atonic bladder 344, 826, 344, ATP-driven proton pump 331, Atresia 477, Atretic follicles 477, Atrial, complex 553, diastole 534, 539, 628, echo beat 568, events 534, description of 534, of cardiac cycle 535f, vs ventricular events 534, extrasystole 554, 567, factor 545, fibrillation 554, 569, flutter 568, kick 536, musculature, as pacemaker 569, depolarization of 553, of heart 446, natriuretic peptide 427, 446, 611,, 793, paroxysmal tachycardia 554, 568, repolarization 553, systole 534, 542, 547, 628, Atrioventricular, block 566, ring 521, valves 522, 539, 542, 545, Atrium, left 650f, , right 650f, Atrophy 19, causes of 19, Attenuation reflex 1009, Audiometer 1023, Auditopsychic area 894, Auditory, association area 894, defects 1022, evoked potential 897, muscles 1009, nerve fiber, action potential in 1020, ossicles 1008, 1009f, pathway 1013, 1014f, radiation 1014, 1014f, tube 1009, Auerbach, nerve plexus 220, plexus 221, Augmented, limb leads 553, secretion of saliva 229, voltage leads 553, Auricle 1007, Auscultation areas 547, Auscultatory method 613, Autoactive action 243, Autocatalytic action 243, Autocrine messengers 368, Autogenic inhibition 912, Autoimmune, atrophic gastritis 240, diseases 119, hemolytic anemia 90, Autologous blood transfusion 147, Automatic bladder 344, pressure instrument 613, Autonomic, functions, regulation of 899, nerve fibers 797, nervous system 758, 954, 956f, 973, divisions of 955t, regulation of 857, Autophagosomes 10, Autoregulation 314, 600, 631, 635, in some vital organs 601, Autorhythmicity 526, Autosomal chromosomes 459, AV nodal, block 566, delay 556, paroxysmal tachycardia 568, rhythm 565, AV node pacemaker 569, Aviation, environment 740, physiology 740, , Axial, filament 472, muscles 834, tomography 635, Axis cylinder 761, Axoaxonic synapse 780, Axodendritic synapse 780, Axolemma 761, Axon 761, depending upon length of 760, hillock 760, reflex 647, terminal 200, Axosomatic synapse 780, Azoospermia 472, Azygos vein 678, , B, B lymphocytes 98, 108, 110, B’schoff employed 149, Babinski, negative sign 799, positive sign 799, reflex 822, sign 799, 817, Back into mouth 271, Bacteria 334, Bainbridge reflex 563, 593f, Ballistic movements, control of 875, Ballistocardiographic method 580, Balloon-tipped multilumen cardiac, catheter 537, Barany chair 927, Barometric pressure 737, 738t, 744t, different depths 743, Baroreceptor, mechanism 607, 608f, 655, reflex 310, Baroreceptors 591, 720, marey reflex 591, Barrier function 23, Bartholin duct 224, Bartter syndrome 329, Basal, body temperature 493, ganglia 835, 878, 879f, disorders of 882, lamina 201, 449, metabolic rate 501, Basement membrane 316, Basilar, artery 634, fibers 1010, membrane 1010, 1011, Basis pedunculus 845, Basket cells 865
Page 1059 :
1038 Essentials of Medical Physiology, Basopenia 101, Basophil 72f, Basophilia 101, Basophilic, cells 376, erythroblast 74, Basophils 98, 104, Bathmotropic, action 523, effect 441, Bathorhodopsin 982, Becker muscular dystrophy 211, Becker-type myotonia or generalized, myotonia 212, Bedwetting 345, 934, Before puberty 466, Belching 240, 280, Belching, act of 280, Belldog experiment 237, Bell-Magendie law 785, 800, Benedict roth apparatus 577, Beneficial effect 180, Benign, enlargement 469, hypertension 614, Bernard-Horner syndrome 998, Beta, adrenergic receptors 441, adrenoceptor blockers 615, antagonists 615, blockers 615, cells 376, hydroxylase 440, receptors 441, 442, rhythm 930, Betz cells 815, 885, 888, Bezold-Jarisch reflex 593, Bicarbonate 713, 714f, buffer system 43, importance of 44, ions 242, mechanism 331, Bickel pouch 235, Biconcave shape of RBCs 66, Biconvex lens 1005, 1006, Bicuspid, area 547, valve 522, Biernacki reaction 83, Bilateral labyrinthectomy 927, Bile, canaliculus 249, pigments 253, properties of 251, salt-activated lipase 244, salts 252, 335, secretion, regulation of 257, , Biliary system 250, 250f, Bilirubin 253, 335, Bilirubinuria 335, Biliverdin 253, Binasal hemianopia 992, Binocular vision 987, Biological, clock 488, 862, tests 508, disadvantages of 508, Biot breathing 732, Biphasic, action potential 192, effect of glucose 417, Bipolar, cells 922, 979, of spiral ganglion 1013, limb leads 552, neurons 759, olfactory receptors 1028, Birth control pills 514, Bitemporal hemianopia 384, 992, Bitter, receptor 1027, taste 1026, Bjerrum 988, Blackout 741, Bleeding, disorders 136, time 135, Blind spot 971, 988, Blindness 396, Blobulin ratio 61, Block, atrioventricular 566, Blocking reactions 121, Blood 58, 335, 441, 487, 501, 666, action on 392, alveoli, diffusion of carbon dioxide, from 708, bank 134, brain barrier 23, 721, 774, 952, 953f, calcium level 405, regulation of 302, 407, 407f, cell volume 149, cells 59, 431, cells, destruction of 153, cerebrospinal fluid barrier 721, 953, clotting 132, 135, 243, coagulation of 127, 129, definition coagulation of 129, deoxygenated 251, 678, effects on 728, 729, 730, 742, flow in various areas of lungs 680f, flow to liver, regulation of 639, flow to skeletal muscles 666, flow to spleen, regulation of 639, flow, chemical factors of 644, , flow, factors determining volume of, 596, gas analysis 577, glucose level 421, glucose level, regulation of 421, group 141f, determination 68, importance of 145, systems 140, groups 139, 140t, 144, 145, indices 86, 87, different 87, importance of 87, level of, calcium 402, phosphate 402, sulfhemoglobin 80, loss 338, phosphate level 405, poisoning 661, pressure 427, 441, 501, 667, 931, after exercise 667, decreases 607, regulation of 302, 606f, 858, properties of 58, reservoir function 153, substitutes 147, supply to, liver 250, pituitary gland 377f, testes barrier 458, tests 297, tissues, diffusion of oxygen from 708, transfusion 146, 662, typing, principle of 140, vessel walls 523t, vessels 393, 441, 523, 639, 955, area of 599, diameter of 597, 605, in fetus 648, of kidneys 312, volume 148, 666, directly proportional to 605, regulation of 150, Bluish discoloration of skin 733, BMR apparatus 577, Body 472, fluids 51, composition of 52, distribution of 51, plethysmograph 694, righting reflexes acting, on body 916, on head 916, shape 478, temperature 359, action on 392
Page 1060 :
Index 1039, decreases 361, increase in 461, increases 361, regulation of 60, 226,355, 361,, 362f, 676, 858, weight 148, action on 392, increase in 501, Bohr effect 506, 713, Bohr effect, double 506, Boilermaker’s disease 1021, Bolus 270, Bondok classification 848, of thalamic nuclei 849t, Bone 400, 402, 431, classification of 409, composition of 409, conduction 1017, diseases of 412, formation 412, growth 411, marrow stromal cells 21, remodeling 411, 412, regulation of 412, resorption 411, salts 409, Bones 378, 406, Bony, canal 1010, labyrinth 919, pillar 1010, Border cells 1011, Borderline diabetes 422, Botulinum toxin 203, Bouveret-Hoffmann syndrome 567, Bowel syndrome 268, 289, Bowman, capsule 306, 328, glands 1028, Boyle’s law of gas 695, Brachia pontis 868, Bradycardia 522, 588, 593, Bradycardia occurs 588, Bradykinesia 882, Bradykinin 104, 611, Bradypnea 723, Brain 285, 653, 757, 932, damage 144, derived neurotrophic growth factor 763, edema 741, natriuretic peptide 427, 446, 611,793, Brainstem 818, 844, Branches of coronary arteries 629, Braxton hicks contractions 503, Breakdown of, acetylcholine 790f, ATP 197, , Breaking point 724, Breast cancer 158, Breast milk 512, advantages of 512, Breath holding 724, Brian burke 806, Bright light vision 980, Broca area 890, Brodmann areas 887, Bronchial, artery 678, asthma 735, causes of 735, circulation 678, veins 678, Bronchopneumonia 734, Bronchospasm 720, Brown adipose tissue 295, Brown fat 295, tissue 360, Brown-Séquard syndrome 823, syndrome of spinal cord 824t, Brucella 226, Brunner glands 262, Brush-bordered cells 306, Buccal glands 224, Bucket handle movement 683, Buffalo hump 435, Buffer action 62, 78, Buffer nerves 593, 607, 608, Buffering action in blood 68, Bulbar, level 957, or medullary reflexes 796, outflow 957, Bulbourethral glands 340, Bulk flow 30, diffusion 705, Bulldog scalp 384, Bullous pemphigoid 25, Bundle, branch block 566, of kent 568, Bungarotoxin 202, Burn shock 660, Bursa of fabricius 108, , C, C cells 404, C wave 628, Cadherins 26, Caisson disease 745, Calcitonin 404, 407, 408, secretion, regulation of 405, actions of 405, Calcitriol 401, , Calcium 406, 1019, alginate 135, blood level of 402, calmodulin complex 208, channel 213, blockers 615, 633, channels 526, 529, deficiency 413, importance of 405, in bones 405, in plasma 405, ion concentration 571, ions 374, 526, 529, metabolism 405, 406f, phosphate crystals 404, rigor 571, Calculated vector 559, Calculation of, blood indices 88, cardiac vector 560f, heart rate 557, mean QRS vector 559, renal blood blow 336, Callosomarginal fissure 886, Calm emotional state 861, Calmodulin 374, Caloric stimulation 927, Calpains 184, Calyx 921, Canal of Schlemm 972, Canalicular system 122, Canaliculi 410, Cancer 289, cells 387, Cane sugar 287, Cannon, A wave 628, sound 545, Capacitance vessels 523, Capillaries 524, 640, dilatation of 647, dimensions of 641, Capillary, bed 642f, bulbs 155, circulation 640, hemorrhage 651, hydrostatic pressure 620, loops 313, arise 646, membrane 675, oncotic pressure 621, plexus 678, pressure 620, definition of 620, direct method of 620, in kidneys 620
Page 1061 :
1040 Essentials of Medical Physiology, in lungs 620, regulation of 620, 621f, to tissue, diffusion of oxygen from 708f, Capsule 972, Capsule, formation of 484, Carbamino compounds 714, Carbamylcholine 203, Carbohydrate, absorption of 264, 287, 288, digestion of 244, 287, 288t, in diet 287, metabolism 287, 289f, 378, 415,, 418, 430, 501, 507, metabolism, action on 392, of cell membrane 6, Carbon dioxide 578f, 727, diffusing capacity for 706, dissociation curve 715, 715f, Carbon monoxide 79, 733, poisoning 79, 733, poisoning, treatment for 734, Carbonic, acid 234, 713, anhydrase 68, 234, 330, 349, Carboxyhemoglobin 79, Carboxyl ester lipase 244, Carboxypeptidases 243, 291, Carboxypeptidases, actions of 243, Carcinogens 8, Carcinomatous myopathy 213, Cardiac, axis 558, 569, branch of vagus 589, bruit 549, catheterization 580, definition of 580, diagnostic uses of 580, performed 580, center 588, cycle 533, 541f, atrial events of 535f, definition of 534, ventricular events of 535f, decompensation 392, disorders 731, end 230, failure 662, coupling of 585, curves 584, curves, analysis of 585, 586f, glands 231, index 573, murmur 549, causes for 549t, muscle 168, 168t, 187, 525, muscle fibers 521f, output 501, 572, 573, 584, 666, 679, , curves 584, definitions and normal values of, 572, directly proportional to 679, distribution of 573, of systolic pressure 604, pulmonary blood flow 679, pain 633, pain, cause for 633, region 230, reserve 573, shock 142, sphincter 230, tamponade 585, vector 558, Cardioaccelerator, center 588, reflex 593, 593f, tone 591, Cardiogenic shock 661, Cardioinhibitory, center 588, 592, 592f, tone 590, Cardiometer 576, Cardiomyopathy. 536, Cardiorespiratory arrest 733, Cardiovascular, adjustments during exercise 664, changes 403, hypertension 614, system 93, 204, 501, 519, 652, 739,, 931, action on 392, effects on 728, 729, 742, Carotid sinus 607, reflex 592, 799, syncope 660, syndrome 564, Carpopedal spasm 403, 403f, 730, Carrier protein, for sodium cotransport 33, of active transport 31, Cartilage 411, cells 411, Caruncula sublingualis 223, Caseinogen 243, Caspases 18, Casts 334, Catabolism 8, Catacrotic, limb 623, notch 623, Catamenia 486, Cataplexy 862, 934, Cataract 973, 976, causes of 976, treatment for 977, , Catecholamines 504, 958, secreted by adrenal medulla 439, Catechol-o-methyltransferase 440, Cathelectrotonic 766, Cathelicidins 102, 116, 676, Cathepsins 184, Catheter 540, ablation 581, Catheterization 537, Catsper 499, Caudal portion 853, Caudate nucleus 878, Cause, antidiuretic effect 610, for adaptation 769, for adaptation of receptor cells 925, for all-or-none law 530, for beneficial effect 180, for cardiac pain 633, for compensatory pause 532, 567, for hypertension 501, for menopause 494, for negativity of intrapleural, pressure 685, for staircase phenomenon 530, for transfusion reactions 142, for ulcerative colitis 269, for unstable resting membrane 206, for vagal escape 590, gastric atrophy 240, myotonia 212, of astigmatism 1005, of coronary occlusion 632, of decompression sickness 744, of hypergonadism in males 466, of hyperinsulinism 424, of motion sickness 927, of multiple sclerosis 826, of pheochromocytoma 442, of postmenopausal syndrome 494, of rigor mortis 183, of second heart sound 546, of stringomyelia 825, of tabes dorsalis 825, Causes, acute renal failure 337, 338, appendicitis 269, chronic renal failure 338, diarrhea 268, drooling 229, for accumulation of gases in, stomach 280, for acquired color blindness 1002, for anemic hypoxia 727, for cardiac murmur 549t, for cell degeneration 20, for conduction deafness 1022
Page 1062 :
Index 1041, for cretinism 396, for dark adaptation 983, for exophthalmos 396, for extracellular edema 161, for fatigue 181, for gallstone formation 260, for haldane effect 715, for histotoxic hypoxia 727, for hypoparathyroidism 403, for hypoxic hypoxia 726, for injury 770, for lymph node swelling 157, for myxedema 396, for necrosis 18, for nerve deafness 1022, for paralysis 837, for primary addison disease 437, for stagnant hypoxia 727, for type II diabetes mellitus 422, for varicose vein 644, for waxing and waning 731, hypertonia 211, hypotonia 211, of abrupt, apnea 732, hyperpnea 732, of acidosis 46t, of acute gastritis 239, of adrenogenital syndrome 436, of alkalosis 47t, of atelectasis 734, of atrophy 19, of auditory defects 1022, of bronchial asthma 735, of cataract 976, of chronic, gastritis 239, pancreatitis 247, of circulatory shock 659, of congenital adrenal hyperplasia 437, of Cushing syndrome 434, of decrease in CO2 in body 46, of diplopia 988, of dysphagia 273, of endocrine disorder 370, of excess CO2 in body 46, of fever 363, of fourth heart sound 547, of gene disorders 14, of gigantism 384, of glaucoma 976, of grand mal 936, of heart failure 662, of hemophilia 136, of hemorrhage 651, of hyperthyroidism 395, of hypogonadism in males 466, , of hypothermia 363, of infertility in, females 496, males 496, of latent period 179, of light adaptation 985, of localized epilepsy 936, of metabolic acidosis 46, of methemoglobinemia 80, of murmur 549, of night blindness 985, of osteomalacia 414, of osteoporosis 413, of Parkinson disease 882, of petit mal 936, of pleural effusion 736, of pneumonia 734, of pneumothorax 734, of presbyopia 1006, of psychomotor epilepsy 936, of pulmonary edema 735, of purpura 137, of recovery 181, of rickets 413, of secondary diabetes mellitus 423, of sneezing reflex 677, of steatorrhea 248, of stroke 637, of third heart sound 546, of thrombosis 137, of type I diabetes mellitus 422, of viral hepatitis 259, of visceral pain 840, of vomiting 276, xerostomia 229, Celiac, disease 248, 265, 472, ganglia 221, Cell 3, adaptation 19, adhesion molecules 26, aging 21, body 979, 980, death 17, degeneration 20, causes for 20, eating 34, junctions 22, 25t, in molecular layer 865, mediated immunity, development of, 110, membrane 4, 4f, 29, 122, 372, membrane, composition of 4, murder 18, signaling 367, suicide 17, volume 86, , Cellophane membranes 346, Cells 418, acidophilic 376, agranular 309, alpha 376, alveolar 675, epithelial 684, argentaffin 261, basket 865, beta 376, Betz 885, 888, bipolar 922, 979, blood 59, chromaffin 439, chromophil 376, chromophobe 376, dendritic 676, enterochromaffin 261, extraglomerular mesangial 309, goormaghtigh 309, lacis 309, of claudius 1012, of fundic glands 231, of Hensen 1012, of martinotti 885, of posterior root ganglia 812, or α-cells 418, precursor 457, secreting hormones 281, Cell-to-cell signaling 367, Cellular enzymes, activity of 392, Cellulose 226, 287, Center for, determining quality of sensations, 851, integration of motor activity 851, light reflexes 995, pain sensation 839, processing of sensory information, 851, psychic-stimuli-induced vomiting, 277, reflex activity 851, righting reflexes 916, sexual sensations 851, Central, apnea 724, arterial pulse 622, canal 950, chemoreceptors 720, connections 830, factors 604, nervous system 151, 431, 442, 757, action on 393, effects on 728-730, manifestations of 424, neuroglial cells 773
Page 1063 :
1042 Essentials of Medical Physiology, scotoma 1002, sulcus 886, veins 251, 617, venous, direct method of 618, pressure 617, Centroparietal thalamic peduncle or, radiation 850, Centrosome and centrioles 10, Cephalic phase 236, 237, 245, Cerebellar, ataxia 211, cortex 865, hemispheres 863, 864, 870, lesions 799, 876, nuclei 865, 868, 868f, peduncles 868f, reflexes 796, Cerebello-olivary tract 872, Cerebelloreticular tract 872, Cerebellovestibular tract 869, Cerebellum 784, 811, 834, 863, anatomical divisions of 864, divisions of 864, functional anatomy of 865, Cerebral, blood flow, regulation of 635, circulation 634, cortex 588, 591, 608, 796, 834, 884, 885, and hypothalamus 588, dominance 886, edema 739, hemispheres 884, hemorrhage 651, ischemia 653, 655, peduncles 845, 991, vascular resistance 635, vessels 634, Cerebro-cerebello-cerebral, circuit 874f, 875f, connections 874, Cerebrocerebellum 873, Cerebropontocerebellar tract 874, Cerebrospinal fluid 636f, 722f, 757, 949, absorption of 950, circulation 952f, collection of 951, composition of 950f, formation of 949, pressure 635, Ceruminous glands 1007, Cervical, cap or diaphragm 514, ganglia 955, lymphatics 950, mucus pattern 493, sympathetic ganglia 590, , Cervix 475, 500, Channelopathies or ion channel, diseases 37, Channels, for major anions 189, regulation of 28, Charcot joint 826, Charge of ions 30, Charles sherrington 906, Chemical, analysis 334, basis of visual process 980, changes muscular contraction 197, composition 274, constitutions 1026, factors 636, 639, of blood flow 644, of pulmonary blood flow 680, mediator 373, messengers 367, 368f, classification of 367, nature 787, of antigens 110, on salivary secretion 228, poisons 96, regulation of respiration 722f, stimuli 775, 840, substances 123, synapse 24, 781, functional anatomy of 781, thermogenesis 362, Chemistry and synthesis 405, Chemistry of, blood level 377, hormones 371, myelin sheath 762, neuromodulators 792, prostaglandins 447, rhodopsin 980, surfactant 684, Chemoattractants 102, Chemokines 116, Chemoreceptor, mechanism 607, trigger zone 276, Chemoreceptors 592, 720, 751, 775, Chemotaxis 101, 114, Chenodeoxycholic acid 252, Chest pain 633, Chewing 270, Cheyne-Stokes, breathing 731, type of periodic breathing 931, Chicken chest 413, Chief sensory nucleus 805, 807, Children 71, Chill 495, , Chime, formation of 232, Chloride, channel diseases 37, shift 714, 714f, space 53, Choke 397, Cholagogue action 253, 255, Cholagogues 257, Cholecystectomy 260, Cholecystokinin 238, 246, 283, 639, 793, action of 247, pancreozymin 236f, 284, Choleretic action 253, 255, Choleretics 257, Cholestatic jaundice 258, Cholesterol 5, ester hydrolase 244, esterase 244, Cholic acid 252, Cholinergic, nerve fibers 765, neurotransmitter 789, Chondrin 411, Chondriocytes 411, Chondroitin sulfate 396, 409, Chorda tympani, fibers 1025, syndrome 229, Chordae tendineae 522, 545, Chorea 852, 883, Choreoathetosis 883, Choroid 968, Christmas disease 136, Chromaffin cells 439, Chromatin 13, Chromatophores 353, Chromophil cells 376, 439, Chromophobe cells 376, Chromophore 980, Chromosomal disorders 15, Chromosomes 13, Chronaxie 177, 177f, 766, Chronaxie, importance of 177, Chronic, adrenal insufficiency 437, angina pectoris 633, demyelinating polyneuropathy 65, diseases 1002, diseases, anemia of 93, gastritis, causes of 239, heart failure 662, 663, hemorrhage 90, 652, 659, pain 838, pancreatitis 247, pancreatitis, causes of 247, progressive chorea 883, renal failure 334, 338
Page 1064 :
Index 1043, Chronotropic, action 522, effect 441, Chvostek sign 404, Chylomicrons 294, Chyme 274, 286, Chymotrypsin 243, 291, Chymotrypsin, actions of 243, Cilia 966, of hair cells 921, Ciliary, body 968, 969, proper 968, ganglion 973, 995, muscle 973, nerves 973, neurotrophic factor 763, processes 968, 971, Ciliospinal reflex 799, 995, Circadian fluctuations of ACTH, secretion 433, Circadian rhythm 433, 444, of ACTH 433, Circadian rhythm, control of 900, Circulation, and drainage of aqueous humor 972f, divisions of 524, of bile pigments 254f, of cerebrospinal fluid 950, 951f, skeletal muscle 644, time 599, time, definition of 599, Circulatory shock 423, 654, different types of 659f, manifestations of 654, treatment for 662, Circumvallate papillae 1024, Circus movement 568, Cirrhosis of liver 150, 259, Cisterna, lateralis 950, magna 950, Cisternae 8, Cisternal puncture 951, Citrates 134, Clara cells 684, Clarke column of cells 805, Clasp-knife reflex 822, 823, Classic hemophilia 136, Classical, heart sounds 544, pathway 114, pills 514, sensory pathways 903, Classification and causes of hypoxia 725, Classification of, anemia 89, 89t, , apnea 724, arrhythmia 562, 565f, bone 409, chemical messengers 367, color blindness 1002, diabetes mellitus 421, fever 363, genetic disorders 14, glands of the stomach 231, hormones depending upon chemical, nature 371t, hypothermia 363, lipoproteins 294, local hormones 447, motor pathways 835, murmur 550, muscles 167, nephrons 305, nerve fibers 764, neuroglial cells 773, neuron 759, neurotransmitters 787, odor 1029, postural reflexes 915, receptors 775, reflexes 796, reticuloendothelial cells 151, salivary glands 224, sensations 829f, synapse 780, Clathrin 35, Cleansing and protective functions 226, Clear cells 404, Climacteric and menopause 494, Clinical, basis 797, importance of BNP 446, thermometer 359, Clock’s pendulum 799, Clonic, convulsions 424, 936, stage 936, Clonus 799, Closed pneumothorax 734, Clostridium, botulinum 203, tetani 182, Clot, definition and composition of 132, retraction 132, Clotting, of semen 467, 468, time 135, Coactivation 888, 914, Coagulation of blood 127, 129, Coal mines, Coarctation of aorta 550, , Cobalt 76, Cobras snakes 135, Cochlea 1010, Cochlea, compartments of 1010, Cochlear, amplifier 1019, division of vestibulocochlear nerve, 1013, duct 1011, fluids 1019, microphonic potential 1019, Cognitive control 881, Cohn’s fractional precipitation, method 62, Cohnheim’s areas 170, Cold 135, blooded 178, animals 359, temperature 183, Colipase 244, Collagen 409, fibers 409, Collagenase 243, Collapse of lungs 734, Collapsing tendency of lungs 684, Collateral ganglia, prevertebral or 957, Collecting, blood in container with smooth, surface 135, ducts 303, 308, 308t, 329, venule 646, Collection of, cerebrospinal fluid 951, gastric juice 239, glomerular filtrate 316, pancreatic juice 247, succus entericus 264, tubular fluid 319, Colloidal osmotic pressure 30, 159,, 317, 318, Colon cancer 25, Colony stimulating factors 106, Color, blindness 1002, 1003, 1003f, blindness, classification of 1002, index 87, 88, of skin 353, sensitive areas in retina 1001, vision 980, 999, Colostrum 511, Columns of bertini 303, Coma 338, 423, 728, Combined pills 514, Comma tract of Schultze 814, Commissural, fibers 868, tracts 807
Page 1065 :
1044 Essentials of Medical Physiology, Common, allergens 120, autoimmune diseases 119, bile duct 250, causes for IDDM 119, causes of rickets and osteomalacia 413t, factors of daily life 80, features of uremia 338, hepatic duct 250, hepatopancreatic duct 250, menstrual symptoms 490, Communicating junctions 23, Compact bone 410, Comparator function 876, Compartments of, body fluids 51, cochlea 1010, Compensated, heart failure 663, stage of circulatory shock 656f, versus decompensated heart failure 663, Compensatory, effects of hemorrhage 651, hypertrophy 20, mechanism 43, pause 532, 567, pause, cause for 532, 567, Complementary colors 1000, Complete, atrioventricular block 566, destruction of pancreas 247, heart block 566, Complex, muscular movements, control of 846, sensations 828, Compliance 687, in relation to intra-alveolar pressure, 687, in relation to intrapleural pressure 687, increase in 688, work 689, Complications in blood vessels 524, Complications of, diabetes mellitus 424, dialysis 347, diuretics 348, mismatched blood transfusion 143f, thrombosis 137, Components of, basal ganglia 878, cerebellum 869t, conductive system in human heart 529, dietary fiber 268, 288, homeostatic system 39, 39f, limbic system 898, 899f, pain sensation 839, tracheobronchial tree 674, , Composite negative electrode 553, Composition breast milk 512, Composition of, aqueous humor 971, 972f, bile 251, 252f, blood 58, body fluids 52, bone 409, cell membrane 4, cerebrospinal fluid 949, 950f, gastric juice 232, 233, inspired air 703, 703t, large intestinal juice 267, 267f, lymph 157f, 158, muscle 175, normal urine 333, pancreatic juice 242, 242f, plasma 59f, prostatic fluid 468, saliva 224, 225, 225f, sebum 356, semen 470, 471f, seminal fluid 467, skeletal muscle 174f, succus entericus 262, 263f, Composition of urine 333, Compound action potentials 192, 193, Compressed air 743, Computerized spirometer 693, Concentrated urine, formation of 325, Concentration equilibrium 189, Concentration gradient 27, Concentration of, bile 256, body fluids 54, gases in expired air 704, lymph 158, urine 325, Concha 1007, Condition of blood vessel wall 625, Conditioned reflex 228, 237, 245, Conditions, altering circulation time 600, apnea occurs 724, asphyxia occurs 730, Bezold-Jarisch reflex occurs 594, biot breathing occurs 732, blood transfusion 146, cardiogenic shock occurs 661, Cheyne-Stokes breathing occurs 732, circulation time prolonged 600, cyanosis occurs 733, dyspnea occurs 730, extrasystole occurs 567, fourth heart sound becomes audible 547, hemolysis occurs 96, hypercapnea occurs 729, , hypoventilation occurs 725, neurogenic shock develops 660, obstructive shock occurs 661, quadruple heart sound 547, Condoms 514, Conduction, deafness 1022, deafness, causes for 1022, method 361, myelinated nerve fiber 768, of impulses 765, Conductive system, in human heart 529, of heart 529f, Conductivity 529, 768, Cone, adaptation 984, dystrophy 985, monochromatism 1002, Confrontation test 988, Congenital, absence of protein C 137, adrenal hyperplasia 437, 437f, adrenal hyperplasia, causes of 437, bleeding disorder 472, hyperplasia 433, immune deficiency diseases 118, Congestive cardiac failure 150, 662, Conjugate movement 975, Conjugated bilirubin 254, Conjunctiva 967, Conn’s syndrome 436, Connections of, basal ganglia 879, 880t, cerebral hemispheres 906, corticocerebellum 873f, different nuclear groups of, thalamus 850t, hypothalamus 856, 857f, limbic system 899, occipital lobe 895, prefrontal cortex 891, primary, auditory area 894, motor area 888, red nucleus 846, respiratory centers 718, reticular formation 902, somesthetic area I 892, spinocerebellum 871f, thalamic nuclei 849, thalamus 849f, vestibulocerebellum 870f, visual receptors to optic nerve 990, Connective tissue 3, 151, Connector neurons 796, Connexins 24
Page 1066 :
Index 1045, Connexons 24, Conscious, kinesthetic sensation 811, 813f, 814,, 829, movements, regulation of 881, Consensual light reflex 994, Consistency of gastric content 274, Constant region 113, Constipation 268, 279, 289, Constituents of flatus 280, Constriction of, afferent arteriole 318, cutaneous capillaries 647, efferent arteriole 318, pupil 985, Constrictor pupillae 968, 973, Contactants 120, Content of, carbon dioxide 708t, 709f, oxygen 708t, 709f, Continuous murmur 550, Contraceptive, methods in males and females 515t, pills 514, Contracted muscle 172f, Contractile, elements of muscle 172, process in smooth muscle 208, proteins 123, 205, strength 214, Contractility 178, 530, Contraction, of glomerular mesangial cells 319, of muscle 575f, period 179, Contrast effects 1001, Control of, Adrenal, cortex 857, medulla 857, anterior pituitary 857, apocrine glands 358, automatic associated movements 881, ballistic movements 875, circadian rhythm 900, complex muscular movements 846, eccrine glands 357, eyeball 846, mastication 270, motor activity 880, muscle tone 846, 880, reflex muscular activity 881, righting reflexes 846, skilled movements 846, smooth muscle 209, somatomotor activities 905, vegetative functions 905, , Controlling cells 367, Conus medullaris 803, of spinal cord 803, Convection method 361, Convergence 786, 786f, Conversion of, fibrinogen into fibrin 130, prothrombin into thrombin 130, Convulsion and convulsive, seizure 935, Convulsions 733, Convulsive muscular contractions 502, Cooley’s anemia or mediterranean, anemia 91, Copper 76, deposits 883, Core temperature 360, Cori cycle 198, 198f, Cornea 967, Corneocytes 351, Corona, ciliaris 968, radiata 483, 499, 815, Coronary, arteries 629, artery diseases 297, 632, blood, flow 631, flow and measurement 630, vessels, distribution of 629, chemoreflex 593, circulation 629, collateral arteries 632, heart disease 268, 289, occlusion 632, cause of 632, definition of 632, perfusion pressure 632, sinus 630, Corpora cavernosa 466, Corpus 230, albicans 486, callosum 884, fibrosa 477, luteum 477f, 485, development of 485, graviditatis 486, menstrualis or spurium 485, of pregnancy 486, spongiosum 340, 466, striatum 878, 879f, Correction of, astigmatism 1006, presbyopia 1006, Corresponding retinal points 988, Cortex 156, 476, Cortex, adrenal 425, 461, 465, 502, , Cortical, auditory centers 1014, center 991, nephrons 305, reflexes 796, Corticocerebellum 865, 872, Corticohypothalamic fibers 856, Corticospinal tracts 814, Corticotropes 376, Corticotropin-releasing, factor 433, hormone 377, 433, Cortisol 504, secretion, regulation of 433f, Cortisone 434, Cotransmission 792, Cotransmitters 792, Cough 675, reflex 677, syncope 660, Coumarin derivatives 133, Counter transport by carrier proteins, 34f, Countercurrent, exchanger 327, 327f, flow 326, mechanism 326, multiplier 326, 326f, system, divisions of 326, Coupling of, cardiac functions 585, vascular functions 585, Coupling reactions 390, Course of visual pathway 990, Coverings of, nerve 761, spinal cord 803, testis 456, Cowper glands 340, Cowpox virus 118, Cracking voice 464, Cranial, content volume, regulation of 950, nerve, fibers 764, nuclei 833, 844, nerves 221, outflow 957, Creatinine 335, clearance 336, Crenation 70, Crescendo and diminuendo series of, waves 548, Cretin vs dwarf 397, Cretinism 396, 397f, Cretinism, causes for 396, Cribriform plate 1028
Page 1067 :
1046 Essentials of Medical Physiology, Crista ampullaris 920, 921, 921f, Criteria for, neurotransmitter 787, for regeneration 772, Critical velocity 596, Croaking sound 396, Crohn’s disease 265, 472, Cross section of, capillary 641f, nerve 761f, Cross-bridges 172, Crossed and uncrossed fibers 810, Crossed extensor reflex 801, 917, Crossed pyramidal tract 817, Crossed spinothalamic tracts 823, 825, Cross-section of muscle 170t, Crude touch 809, sensation 807, Crush syndrome 659, Crushing, injury 822, or local anesthetics 192, Cryoablation 581, Cryptorchidism 461, 463, Crypts of lieberkühn 261, Crystalline 972, Crystals 334, C-type natriuretic peptide 427, 446, 611, Cuneocerebellar tract 871, Cupula 921, Curare 202, Current of injury 569, Cushing, disease 385, reaction 636, reflex 636, 636f, syndrome 385, 434, 435, 435f, adrenal origin of 435, causes of 434, treatment for 436, Cutaneous, blood flow, regulation of 646, capillaries, constriction of 647, circulation 646, distribution 830f, receptors 775, 776f, reflexes or skin reflexes 797, Cuticular plate 921, 1011, Cyanocobalamin 75, Cyanopsin 983, Cyanosis 733, Cyanosis, distribution of 733, Cycle of waxing and waning 732f, Cyclic, adenosine 313f, AMP 373, guanosine monophosphate 374, , Cylindrical glass 1006, Cysteine 43, Cystic, duct 250, fibrosis 247, Cystometrogram 342, 342f, definition 342, description of 342, Cytoarchitecture 887, Cytochrome, C 18, system 729, Cytokines 16, 104, 115, 117t, 354, Cytoplasm 4, 6, 123, 372, of neutrophils 102, Cytoplasmic organelles 7, Cytoskeleton 11, 67, , D, D cells of, pancreatic 285, stomach 285, Damage of blood-testes barrier 458, Damping action 875, Danielli-Davson model 4, Dark, adaptation 983, causes for 983, curve 984, 984f, band 171, current 982, Daylight vision 980, D-E segment 543, Dead, cells 351, space 701, definition of 701, Deafness 854, Death 728, formation 747, receptor ligands 18, receptors 18, Decapeptide 310, Decarboxylation 440, Decarboxylation cells 281, Decay of tissues 747, Decerebrate, preparation 906, rigidity 906, 912, Decerebration in man 907, Decidua 499, Decidual cells 499, Decompensated heart failure 663, Decompression sickness 744, Decompression sickness,, cause of 744, , Decorticate, preparation 906, rigidity 906, Decrease in, cardiac output 573, 585, compliance 688, muscle tone 880, PCV 87, RBC count 69, Decreased, hemoglobin content in blood 727, number of RBCs 727, sperm count 496, Decreasing catabolism of protein 378, Deep, reflexes 797, 798t, sea physiology 743, sensations 829, sleep 930, Deeper, structures 839, veins 646, Defecation 278, act of 279, reflex 279, 279f, Defective dim light vision 985, Defense, macrophages 676, mast cell 676, mechanism 675, natural killer cell 676, Defensins 102, 116, 261, 262, 676, function 60, mechanism 432, Definition, and cause 729, cystometrogram 342, Degenerative, changes in neuron 771, chorea 883, Deglutition 270, apnea 271, 724, 677, center 844, definition 270, reflex 272, 677, Degradation of worn-out organelles 8, Dehydration 55, 318, exhaustion 747, in infants 56, shock 660, Dehydroepiandrosterone 462, Dehydrotestosterone 462, Deiodinase 397, Delayed, conduction 566, effects of hypoxia 728, pulse 625
Page 1068 :
Index 1047, Delirium 735, Delivery of materials 9, Delta, rhythm 930, waves 932, Dementia 882, Demonstration of refractory period in, heart 531, Demyelination 826, Dendrite 761, Dendritic cells 110, 676, Denervation hypersensitivity 212, Dense, bodies 205, granules 123, Dentate nucleus 868, Dentatorubral tract 874, Dentatorubrothalamocortical, tract 874, Dentatothalamic tract 874, Deoxygenated blood 251, 678, Deoxyribonucleic acid 14, Depletion of neurotransmitter 785, Depolarization 190, Depolarization of atrial, musculature 553, Depression 974, Depressor area 588, Derivation of Weber-Fechner law 777, Derivative of amino acid 252, Dermal 353, Dermatomal rule 840, Dermis 352, Dermographism 647, Descending, facilitatory reticular system 904, inhibitory reticular system 905, limb 307, reticular system 904, tracts of spinal cord 814, 816t, Descent of testes 463, Desmin 173, Desmosome 25, Desquamated 486, Destruction of, acetylcholine 202, 449, blood cells 153, hemoglobin 81, 152, nerve cell 895, sensory nerve fibers 344, Desynchronization 930, Desynchronized waves 930, Detergent action 252, Determination of, ABO group 140, acid-base status 43, ESR 83, , Determining, compliance 687, ESR 84, ovulation time 493, PCV 86, PEFR 697, synaptic delay 785, Detoxification 8, 10, functions 256, Detrusor muscle 339, Deuteranomaly 1003, Deuteranopes 1003, Deuteranopia 1003, Deuterium oxide 53, Development of, central nervous system 393, EPSP 782, receptor potential 778, Deviation movement 876, Dexamethasone 434, Dextrin 226, Dextrinase 287, Diabetes, insipidus 329, 334, 363, 382, 387, 862, mellitus 329, 334, 421-423, causes of type I 422, causes of type II 422, classification of 421, diagnostic tests for 424, treatment for 424, Diabetics 289, Diabetogenic hormones 421, Diacylglycerol 374, Dialysate 346, 347, Dialysis 346, Dialysis, principle of 347f, Diameter of blood vessels 597, 605, Diapedesis 101, Diarrhea 268, 428, Diastolic, blood pressure 441, 603, heart failure 663, murmur 550, pressure 441, 613, in different age 603, Dichromatism 1003, Dichromats 1003, Diencephalon 847, 855, Dietary, abuse 268, causes 268, fiber 267, 268, 269, 288, iron 82, source 406, Differences between, electrical potential in nerve fiber and, muscle fiber 767t, , extracellular fluid and intracellular, fluid 53t, insulin and glucagon 419t, liver bile and gallbladder bile 252t, neurotransmitters and, neuromodulators 791t, type I and type II diabetes mellitus, 422t, WBCs and RBCs 98t, Diffuse, pathway 990, secondary evoked potential 897, Diffused ganglionic cells 990, Diffusing capacity 706, Diffusion of carbon dioxide 708, Digeorge syndrome 118, Digestion of, carbohydrates 244, 287, 288t, lipids 243, 293, 294t, milk 243, proteins 242, 290, 290t, Digestive enzymes of, gastric juice 233t, pancreatic juice 245t, saliva 226t, succus entericus 263t, Digestive, function 226, 232, 255, 262, 263, functions of pancreatic juice 242, organs, accessory 220, peristalsis 274, system 204, 219, 301, 502, 739, effects on 728, functional anatomy of 219, Dihydroxyphenylalanine 439, Dilatation, and curettage 515, of arterioles 647, of capillaries 647, of pupil 799, 983, Dilator pupillae 968, 973, Dilute urine, formation of 325, Dim light vision 980, Dimensions, and details of capillaries 641t, of capillaries 641, of RBC 67f, of structures in skeletal muscle 171t, Diopter 978, Dipalmitoylphosphatidylcholine 684, Dipeptidases 291, Diplegia 837t, Diploid, cells 13, number 459, Diplopia 988, Diplopia, causes of 988
Page 1069 :
1048 Essentials of Medical Physiology, Direct, actions of antibodies 114, corticospinal tract 817, light reflex 994, spinocerebellar tract 811, Directly proportional 574, 596, to resistance 618, Disaccharides 287, Disappearance of muffled sound 613, Discrimination of different taste, sensations 1026, Discriminative nature 851, Disease, addison 437, Boilermaker’s 1021, christmas 136, Hodgkin 93, 472, Alzheimer’s 18, 21, 763, Diseases, involving muscle tone 211, of bone 412, of spinal cord 825, potassium channel 37, Disjugate movement 975, Disk prolapse 826, Disorders of skeletal muscle 210, Distal, convoluted tubule 308, 329, muscles 834, Distant vision 986, Distribution, apocrine glands 357, depending upon 764, eccrine glands 357, of blood flow 638, of blood pumped out of left ventricle, 574, 574t, of body fluids 51, of single-unit smooth muscle fibers 206, Distributive shock 660, Disturbances, in equilibrium 876, in posture 876, in tone 876, of acid-base status 45, Diuresis 609, Diuretic agents 348, Diuretics 348-350, abuses of 348, complications of 348, Diurnal variation in melatonin, secretion 444, Divergence 786, 786f, Diverticulum 376, Divisions of, autonomic nervous system 954, 955t, cerebellum 864, , circulation 524, countercurrent system 326, internal capsule 853, nervous system 757, pituitary gland 375, reticular formation 902, trigeminal nerve 830f, uterus 474, visual field 987, 988f, Dizziness 927, Dominant or categorical hemisphere 886, Dominators 1000, Donor 141, Dopa decarboxylase 440, Dopamine 442, 790, 882, injection 883, Doppler, echocardiography 579, effect 576, flowmeter 630, principle 579, Dormitory effect 358, Dorsal, cochlear nuclei 1013, funiculus 806, nucleus of, clarke 805, 811, vagus 589, respiratory group of neurons 716, spinocerebellar tract 811, 871, white column 806, Dotted lines indicate contraction of, detrusor muscle 342f, Double, antigen-antibody reactions 509, feedback control 488, vision 988, Douglas bag 694, 704, Down’s, regulation 372, syndrome 211, Downward movement 974, Drags actin filament 195f, Drainage of lymphatic system 155, Drinker method 750, Dromotropic, action 523, effect 441, Drooling 229, Drug-induced parkinsonism 882, Drugs 80, 1002, Drugs, act on muscarinic receptors 959, antiarrhythmic 564, induce bradycardia 588, inducing release of, noradrenaline 958, , on salivary secretion 228, prolong action of ACH 959, stimulating, neuromuscular junction 203, receptors directly 958, Drum-beating tremor 882, Duchenne muscular dystrophy 211, Duct of santorini 241, Duct system of salivary glands 224, Ductless glands 368, Ducts of, arteriosus 648, 626f, 650f, arteriosus, closure of 650, bellini 303, 308, deferens 456, major salivary glands 224t, reuniens 920, 1011, rivinus 224, venosus, closure of 650, Ductus, arteriosus 650, venosus 650, Dudgeon sphygmograph 623, Dumbbell shaped 66, Duodenal ulcer 240, Duodenum 282, 284, Dural sinuses 950, During sleep 69, Dwarfism 377, 385, 387, in dystrophia adiposogenitalis 386, in panhypopituitarism 386, Dye, dilution method 578, phenol red 323, Dynamic, compliance 687, exercise 664, gamma efferent 910, lung function tests 690, response 911, Dynein 36, motor molecules 37f, Dynorphins 792, Dysarthria 877, Dysdiadochokinesia 877, Dysfunction of myenteric plexus 269, Dysgeusia 1027, Dysmenorrhea 491, Dysmetria 877, Dysphagia 273, Dysphagia, causes of 273, Dysplasia 20, Dyspnea 723, 730, point 730, venous engorgement 392, Dyspneic index 731, Dystrophia adiposogenitalis 387, 862
Page 1070 :
Index 1049, , E, Ear dust, otoconia or statoconia 922, Early, dumping 275, normoblast 74, Eaton-Lambert syndrome 203, Ecchymoses 136, Eccrine glands 357, control of 357, sweat glands 357t, ECG, changes 562, 563, 564, in sinus arrhythmia 563f, in sinus bradycardia 564f, in sinus tachycardia 564f, leads 552, ECG 535 See Echocardiography, Eclampsia 502, Eclampsia, treatment for 502, Ectodermal 375, Ectopic, arrhythmia 564, arrhythmia, different 565, pacemaker 567, pregnancy 87, Edema 159, 160, 338, to heart failure 161, to increased endothelial permeability, 162, to inflammation of tissues 161, to lymphatic obstruction 161, to malnutrition 160, to poor metabolism 161, to renal diseases 161, Edinger-Westphal nucleus 957, 973, 995, Edridge-Green lantern 1003, EEG 929, EEG during sleep 930, Effective, osmolality 55, perfusion pressure 600, 635, Effector organ 795, Effects, of asphyxia 730, of atelectasis 734, of caloric stimulation 927, of catecholamines 442, of disorders of sensory pathways 833t, of emphysema 736, of exercise on, cardiovascular system 666, respiration 751, of expansion of gases on the body, 738, of exposure to, cold 746, , and heat 746, heat 747, severe cold 746, of extirpation of testes 465, of gravitational forces on body 740, of hemisection 824, of hypercalcemia 404, of lesion of optic tract 992, of lower motor neuron lesion 836t, of travel by spacecraft 741, of two successive stimuli 180, of upper motor neuron lesion 836t, on blood 728, 729, 730, 742, on cardiovascular system 728,, 729, 742, on central nervous system 728-730, on digestive system 728, on immune system 742, on musculoskeletal system 742, Efferent, arteriole 313, arteriole, constriction of 318, connections 869, 870f, 872,, 873f, 888, hypothalamus 856, of red nucleus 846f, of reticular formation 903f, fibers 272, to ciliary muscle 998, to medial rectus 998, nerve 795, fibers to hair cells 922, 1013, pathway 718, 998, vessels 156, Efficacy of oxygen therapy in different, types of hypoxia 729, Effort syncope 660, Egg 290, 476, Eicosanoids 447, Einthoven, law 560, triangle 552, 559, 560f, See, Einthoven law, willem 551, Ejaculation 470, Ejaculatory ducts 340, 456, Ejection, fraction 535, 573, period 535, 539, 543, Elastase 243, Elastic, property of lung tissues 684, reservoir 598, resistance of, lungs 689, of thorax 689, , Electrical, activity in, multiunit smooth muscle 207, single-unit smooth muscle 206, and chemical synapse 781f, basis of visual process 985, gradient 27, of substance 29, mapping 581, potential 1019, in hair cells 924, in SA node 528, in cardiac muscle 525, property 786, synapse 780, Electrocardiogram 551 See ECG, Electrocardiographic grid 552, Electrocardiography, definitions of 551, Electrochemical, downhill gradient 320, uphill gradient 320, Electroencephalogram 929 See EEG, Electroencephalograph 929, Electrogenic activity 32, Electrolyte, balance 355, concentration on heart 570, equilibrium 714, Electromagnetic, flowmeter 576, 630, probe 576, Electromyogram 210, Electromyographic technique 210, Electromyography, definition 210, Electron microscopic study of, sarcomere 171, Electronegativity 982, Electronic, device 569, pulse transducer 623, transducer 627, vibrator 1023, Electrophoretic method 61, Electroretinogram 985 985f, See ERG, Electrotonic potential 766, 767, Electrotonic potential, properties of 767, Elephantiasis 161, Elevated jugular venous pulse 628, Elliptocytosis 70, Embden-Meyerhof pathway 197, Emboliform nucleus 868, Embolism 137, 524, Embolus 137, Embryo 62, Embryonic stem cells 21, Emesis 276, Emmenia 486
Page 1071 :
1050 Essentials of Medical Physiology, Emmetropic eye 998, 1004, Emotional, changes 860, 882, conditions 69, fainting 660, instability 891, outbursts 936, Emphysema 736, Emphysema, development of 736, Emptying of stomach 274, Emulsification of fats 252, Emulsion in small intestine 252, End disk or end ring centriole 472, End of contraction 199, End-diastolic volume 536, 542, Endemic colloid goiter 397, Ending of axon 780, Endocardium 522, Endocochlear potential 1019, Endocrine, disorder 370, disorder, causes of 370, function 241, 302, 506, of other organs 444, of pancreas 415, of testes 461, of thymus 445, glands 368, 369, action on 393, regulation of 899, hypertension 614, messengers 367, or secondary hypertension. 443, system 502, Endocrinology 367, Endocytosis 33, Endogenous, analgesic system. 841, gases 280, opioid peptides 792, Endolymph 924, 1010, 1019, Endolymphatic, potential 1019, sac 920, Endometrium 475, 480, 486, Endomysium 169, Endopeptidases 243, 291, Endoperoxide 447, Endoplasmic reticulum 6, 8f, 234, Endorphins 792, Endosmosis 95, Endothelial cells 641, Endothelium 209, 705, derived relaxing factor 209, 612, of blood sinusoid 151, Endotoxin shock 661, Endplate potential 202, , development of 201, properties of 201, End-systolic volume 535, 542, Endurance of muscle 214, 215, Energy for muscular contraction 196, Enkephalins 792, Enlargement of, heart 742, muscles 211, prostate gland 469, spinal cord 803, Enophthalmos 998, Enteric, nerve endings 286, in small intestine 286, nervous system 221, Enteritis 265, Enterochromaffin cells 261, 282, Enterocytes 261, Enteroendocrine cells 232, 281, Enterogastric reflex 238, 275, Enterohepatic circulation 251, 251f, of bile salts 252, Enterokinase 243, Enteropeptidase 243, Entrance of bolus into, esophagus 271, Entry of sperm into uterus, prevention, of 514, Enuresis 344, Environmental temperature 69, Enzyme, angiotensin-converting 310, cascade theory 129, Enzymes 11, 123, amylolytic 262, 287, of gastric juice, actions of 233, Eosinopenia 101, Eosinophil 72f, cationic protein 104 See ECP, derived neurotoxin 104, peroxidase 104, Eosinophilia 100, Eosinophils 98, 102, Epicardium 521, Epicritic sensations 828, Epidermis 351, Epididymis 456, 457, Epigastric pain 240, Epilepsy 929, 935, Epileptic 935, aura 935, Epimysium 169, Epiphyseal, cartilage 409, fusion 378, 411, plate 409, 411, , Epithelial, cells 286, 334, lining 220, sodium channel 1027, tissue 3, Epithelium of respiratory unit 705, Epstein-Barr virus 147, Equalizing pressure 1017, Equilibrium 913, Equipment for voltage clamping 767, Erb, sign 404, Westphal sign 404, Erlanger-Gasser classification 765, Errors of refraction 986, 1004, 1005f,, 1006f, Erythema 432, Erythroblastosis fetalis 143, Erythroblastosis fetalis, treatment for 144, Erythrocyte, sedimentation rate 83, volume fraction 86, Erythrocytes 66, Erythropoiesis 71, 72, 74t, Erythropoiesis, definition of 71, Erythropoietic, action 464, activity 267, Erythropoietin 68, 75, 445, Erythropoietin, actions of 75, Escape phenomenon 427, 446, Escherichia coli 268, Esophageal, achalasia 273, balloon 687, stage 272, stage or third stage 271, ultrasonic doppler transducer, technique 579, ESR, determination of 83, Essential, endocrine glands 425, hypertension 614, Estimation of, plasma proteins 335, urea 335, Estradiol 462, Estrogen 433, 460, 477, 488, 506, 510, binding protein 458, induced cancer 495, receptors 479, secretion, regulation of 479, 479f, Ethylenediaminetetraacetic acid 134, Etiological classification of anemia 90t, Eukaryotes 13, Eunuchism 465, Eustachian tube 1009
Page 1072 :
Index 1051, Evacuation of accumulated gases 280, Events of, cardiac cycle 534, 537f, neuromuscular transmission 201, urine formation 316f, Evoked, cortical potential 895, potential 895, 897, Exaggerated allergic reaction 661, Examination of, blood 335, radial pulse 624, urine 333, 335, venous pulse 627, Examples of referred pain 840, Excess worries 393, Exchange of, gases 6, respiratory gases 705, in lungs 705, transfusion 147, Excitability 176, 525, 766, curve 177, definition of 176, 525, Excitation, contraction coupling 194, 195f, of hair cells 1018, Excitatory, function 782, neurotransmitters 788, postsynaptic potential 782, 788, Excretion 406, of bile pigments 254, of calcium 406, of hydrogen ions in combination with, ammonia 332f, phosphate ions 332f, of waste products 301, Excretory, function 6, 60, 226, 232, 255, 267,, 355, 505,, system 502, 931, Exocrine, function 241, part of pancreas, functional anatomy, of 241, Exocytosis 35, Exogenous, gases 280, steroids 434, Exopeptidases 243, Exophthalmos 396, causes for 396, on vision 396, Expansibility of, lungs 687, thorax 687, , Experiment to prove frank 184, Expiration 674, Expiratory, center 717, muscles 683, accessory 683, neurons 717, reserve volume 691, 691f, 693f, Expired air 703, 703t, 704, Expired air, definition of 704, Exposure to industrial chemicals 80, Extensor reflexes 796, External, anal sphincter 220, 279, auditory, canal 677, meatus 1007, ear 1007, elastic lamina 523, genitalia 456, 463, 474, granular layer 885, limiting membrane 969, medullary lamina 879, or communicating hydrocephalus 953, OS 475, respiration 673, urethral sphincter 341, Exteroceptors 775, 776f, Extirpation 369, of testes in adults 466, Extorsion 974, Extra-adrenal pheochromocytoma 442, Extracapsular extraction 977, Extracardiac pressure on cardiac output, curve 585, Extracelluar, edema 161, edema, causes for 161, electrode 767, fluid 202f, 313f, 428f, 606f, 861f, volume 427, Extracts of lungs 135, Extrafoveal vision 971, Extrafusal fibers 806, 888, 915, Extraglomerular mesangial cells 309, Extrahepatic, bile ducts 250, biliary apparatus 250, jaundice 258, Extrapyramidal, pathways 835, system 889, tracts 818, 835, Extraspectral colors 1000, Extrasystole 567, Extrinsic, muscles 973, , of eyeball 974f, innervation of 973, nerve supply 221, to GI tract 222f, Eye, socket 966, sty 966, Eyeball, control of 846, movements of 846, during accommodation 996, movements of 846, Eyelids 966, , F, Face 839, Facilitate movements 870, Facilitated diffusion 288, 291, Facilitation of, centers for micturition 343, responses 800, somatomotor activities 904, vegetative functions 904, F-actin 173, Factors, affecting, cardiac output curves 584, diffusing capacity 706, ESR 85, force of contraction 179, gastric emptying 274, oxygen 713, physiological functions 738, rate of diffusion 29, respiratory centers 719, 721f, spermatogenesis 460, vasomotor center 591, causing collapsing tendency of, lungs 684, controlling capillary circulation 643, decreasing ESR 85, determining viscosity 597, increasing, ESR 85, GFR vasodilatation 319, Influencing, Bohr effect 713, gastric secretion 239, involved in blood clotting 129, maintaining, arterial blood pressure 604, cardiac output 574, velocity 599, necessary for, erythropoiesis 74, hemoglobin formation 76
Page 1073 :
1052 Essentials of Medical Physiology, leukopoiesis 106, preventing collapsing tendency of, lungs 684, regulating, blood flow to skeletal, muscle 644, bone remodeling 413t, coronary blood flow 631, vagal tone 594f, venous pressure 618, stimulating secretion of hydrochloric, acid 234, Facultative reabsorption 382, of water 328, Fallopian tube 500, False labor contractions 503, Far point 998, Farrel and Ivy pouch 235, Fascia 169, Fasciculi 169, Fasciculus 761, cuneatus 813, dorsolateralis 812, interfascicularis or comma tract of, schultze 813, Fast, pain fibers 839, synaptic transmission 788, Faster conduction 762, Fastigial nucleus 868, Fastigiobulbar tract 869, 872, Fasting and exercise 285, Fat 284, 285, cells 294, 295, metabolism 378, 416, 419, 430, 479, action on 392, Fatal disease 614, Fate of, adrenocortical hormones 426, conjugated bilirubin 254, corpus luteum 485, corticosteroids 426, osteoblasts 411, RBC 68f, red blood cells 67, Fatigue 181, 785, 801, causes for 181, curve 181, 182, Fats, absorption of 253, 264, addition of 158, Fatty, acids, re-esterification of 293, liver 378, 392, Faulty techniques during blood, transfusion 147, Feces, formation of 267, , Female, gamete 476, genital tract 468, reproductive organs 473, 473f, 474f, urethra 340, 341f, urinary bladder 341f, Femoral, artery 623, delay 625, Fencing function 23, Fenestra 952, vestibuli 1010, Fenestrae or filtration pores 306, 316, Fermentable components 267, Fern pattern 493, Ferrihemoglobin 79, Fertility control 513, Fertilization 467, of ovum 498, Festinant gait 882, Fetal, circulation 648, 649f, hormones 503, life 71, lungs 648, 673, respiration 648, Fetoplacental unit 507, 507f, Fetus 464, Fever 362, causes of 363, classification of 363, F-G segment 543, Fibers, of internal capsule 854t, to cerebellum 922, Fibrillation and denervation, hypersensitivity 212, Fibrils or regenerative sprouts 772, Fibrinolysin 487, Fibrinolysis 132, 132f, Fibrin-stabilizing factor 123, Fibroblast growth factor 763, Fibrocartilaginous plate 1007, Fibrosa 221, Fibrous, astrocytes 773, layer 521, proteins 12, Fick, law of diffusion 707, principle 577, 630, 634, to measure cardiac output 577, Field of vision 987, definition of 987, Fifth degree of injury 771, Fight and flight reactions 442, 638, Filiform papillae 224, 1024, , Filtered load 330, Filtering membrane in renal corpuscle 306f, Filtration 30, 159, action 675, coefficient 317, fraction 316, membrane 316, of substances 643, Filum terminale 803, of spinal cord 803, Fimbriated end 498, Final, common path 865, of cerebellar cortex 865, common pathway 834, 834f, products of, carbohydrate digestion 287, fat digestion 293, protein digestion 291, repolarization 526, ventricular complex 556, Fine touch sensation 813f, Firing level and depolarization 191, First, breath of child 649, degree 770, heart block 566, heart sound 535, 544, 545, 548, and ECG 545, order neuron 1014f, order neurons 807, 813, 839, 922,, 989, 1013, 1025, period of sexual life in females 475, stage or, compensated stage 655, rapid ejection period 535, Fissure 804, Fissures present over surface of, vermis 864, Fixed reticuloendothelial cells 151, Flaccid 344, neurogenic bladder 344, paralysis 821, Flare 647, Flat bones 71, Flatulence 280, Flatus 280, Flatus, constituents of 280, Flechsig tract 811, Flexor reflexes 796, Flight of ideas 891, Flocculi 863, 869, Flocculonodular lobe 863, 869, of cerebellum 864, Flow of, blood to lungs 649, lymph 158
Page 1074 :
Index 1053, Flowmeter 576, 599, Fludrocortisone 434, Fluid, filled cavities 825, loss 150, mosaic model 5, of growth 58, of health 58, of life 58, Fluoroscopic observation 580, Focal, adhesion 25, epilepsy or local seizure 936, Folic acid 76, Follicles 388, Follicles, different 483, Follicle-stimulating hormone 380, 461f,, 489f, Follicular, cavity or antrum 483, cells 388, phase 483, 488, sheath 484, Follicule-stimulating hormone 460, Food, intake, regulation of 900, intolerance 268, substances 120, Footplate 1009, Foramen of, Luschka 950, Magendie 950, Monro 950, ovale 648, 650f, closure of 649, Force of, contraction 575, contraction of heart 392, Forced, breathing 719, expiratory volume 696, 698f, vital capacity 696, Forel decussation 845, Formation, of bile pigments 254, of altered hemoglobin 727, of aqueous humor 971, of bile, pigments 254f, salts 252, 253f, of blood cells 153, of bradykinin from HMW kinogen, 451, of camp 373, Formula to determine resistance 597, Fornix 856, Forward into larynx 271, , Fourth, degree of injury 771, heart sound 534, 547, 548, and ECG 547, causes of 547, Fovea centralis 971, Foveal vision 971, Fractional, gastric analysis 239, test meal 239, Fracture of bones 741, Fractures 479, Fragility 95, test 95, Fragment crystallizable 113, Frank-Starling law 184, 575, Free, bilirubin 254, endings 782, histiocytes of solid tissue 152, load 184, vs after load 184, nerve ending 912, Frequency, and duration of dialysis 346, of stimuli necessary to cause tetanus, and clonus 182, theory 1020, Friedman test 508, Frog’s heart 528f, Fröhlich syndrome 386, 387, 466, 862, Frontal lobe, areas and connections of 892t, of cerebral cortex 887, syndrome 891, Frostbite 747, Fructose 467, absorption of 288, FSH, actions of 380, Full-blown diabetes mellitus 378, Function, depending upon 764, 788, generator 1023, of area 4 888, of artificial kidney 346, of broca area 890, of L-tubules 175, of mucus 233, of otolith organ 926, of parasympathetic fibers 227, 341, of pudendal nerve 342, of saccule 926, of supplementary motor area 891, of sympathetic, fibers 227, nerve 341, of T-tubules 175, of utricle 926, , Functional anatomy 241, 261, 369, of biliary system 249, of eyeball 966, of liver 249, of mouth 223, of ovary 476, of respiratory tract 674, of stomach 230, of testes 456, of urethra 339, of urinary bladder 339, of vestibular apparatus 920, Functional, classification of synapse 780, difference 78, divisions of reticular formation 904f, gateway for cerebral cortex 851, hyperemia 639, regions on lateral surface of cerebral, cortex 887f, residual capacity 691f, 692, 693f, and total lung capacity 694, significance 796, of apoptosis 17, Functions of, absorptive 6, ANS 958, aqueous humor 972, astrocytes 774, auerbach plexus 221, basal ganglia 880, bile 255, blood 60, brain barrier 458, 952, bone 409, brown adipose tissue 296, capillaries 642, carbohydrates in cell, membrance 6, cell membrane 6, cerebellum 875f, cerebrospinal fluid 950, cones 980, corpus luteum 485, cortical, auditory centers 1015, lobes 896t, cutaneous circulation 646, cytoplasmic organelles 7t, dietary fats 293t, different antibodies 114, estrogen 478, exchange of gases 6, excretory 6, fetoplacental unit 507, gallbladder 256, gap junction 24
Page 1075 :
1054 Essentials of Medical Physiology, gastric, glands 232, juice 232, Golgi, apparatus 8, tendon organ 911, hemoglobin 77, hydrochloric acid 234, hypothalamus 857, 858t, intermediate filaments 12, intrapleural fluid 674, juxtaglomerular apparatus 310, kidney 301, large intestinal juice 267, large intestine 267, limbic system 899, lipid layer in cell membrane 5, lipoproteins 295, 295t, liver 255, lymph 158, nodes 157, lysosomes 9, maintenance of shape and size of, the cell 6, meissner plexus 221, microfilaments 12, microglia 774, microtubules 12, mineralocorticoids 426, mitochondrion 11, molecular motors 36, motor neurons 834, mouth 223, muscle spindle 910, myelin sheath 762, natural killer cell 115, nerves supplying urinary bladder and, sphincters 341t, neurilemma 762, nucleus 13, occipital lobe 895, oligodendrocytes 774, osteoblasts 410, osteoclasts 411, osteocytes 411, ovaries 477, pancreatic juice 242, parasympathetic nerve fibers 222, peroxisomes 10, pineal gland 444, placenta 505, plasma proteins 62, platelets 124, pons 845, pontine 819t, prefrontal cortex 891, primary, , auditory area 894, motor area 888, progesterone 480, prostatic fluid 468, protective 6, proteins in cell membrane 6, red, blood cells 68, nucleus 846, reticular formation 903, reticuloendothelial system 152, ribosomes 11, rods 980, rough endoplasmic reticulum 8, sarcotubular system 175, satellite cells 774, Schwann cells 774, sebum 356, selective permeability 6, semicircular canals 923, seminal fluid 467, sertoli cells 458, skin 354, small intestine 263, smooth, endoplasmic reticulum 8, muscle 204, somesthetic, area I 892, area II 893, association area 893, spleen 153, stomach 232, succus entericus 262, sympathetic nerve fibers 221, synapse 782, testes 458, testosterone 462, in adult life 462, 463, thalamus 851, thymus 445, thyroid hormones 391, tight junction 23, tissue fluid 159, vestibular apparatus 923, white, adipose tissue 295, blood cells 102, Fundic glands 231, or main gastric glands or oxyntic, glands 231, Fundus 230, 971, oculi 971, 971f, Fungiform papillae 1024, Fuscin 969, Fusiform cell layer 885, Fusion of epiphysis 384, , G, G cells 282, G protein 982, gustducin 1026, G-A segment 543, GABA, action of 783, G-actin 173, Gait 882, Galactose, absorption of 288, Galea capitis 471, Gallbladder 249, 256, filling and emptying of 256, Galli-Mainini test 508, Gallop rhythm 547, Gallstone, diagnosis of 260, formation, causes for 260, prevention of 253, 255, treatment for 260, Gallstones 260, 268, 289, definitions 260, formation of 260, Gametogenic functions of testes 458, Gamma motor neurons 833, 913, Gamma-aminobutyric acid 789, 791, Ganglion cell layer 970, Ganglionic, blockers 959, cells 970, layer or internal pyramidal, layer 885, Gap junctions 23, 24f, 521, Gases, diffusing capacity of 740, from gastrointestinal tract 279, from guns and other weapons, in arterial 711t, in intestine 280, Gastrectomy 275, Gastric, analysis 239, atrophy 240, atrophy, cause 240, content, consistency of 274, dumping syndrome 275, emptying, abnormal 275, regulation of 274, glands 231, 231f, inhibitory peptide 236f, 238, 284, juice, collection of 239, composition of 232, 233, digestive enzymes of 233t, properties of 232
Page 1076 :
Index 1055, lipase 232, or tributyrase 293, phase 237, 246, pits 231, secretion 238, secretion, regulation of 234, ulcer 240, Gastrin 282, 283, 639, on gastric secretion, actions of 237, releasing polypeptide 282, Gastritis 239, Gastrocnemius-sciatic preparation 178, Gastrocolic reflex 279, Gastroenteric reflex 278, Gastroenterostomy 275, Gastroesophageal reflux disease 273, Gastrointestinal, hormones 238, 281, 282, 282t, 286,, 450, description of 282, tract 219, 220f, 401, 402, 931, action on 393, activity of 638, somatostatin 420, Gastroparesis 275, Gate, control 843, system 842f, theory 841, function 23, Gated channels 28, Gel filtration chromatography 62, Gelatinous cupula 924, Gelatinous tectorial membrane 1011, Gene 14, disorders, causes of 14, expression 16, General, characteristics of cell 3, metabolic processes in testis 460, static reflexes or righting reflexes, 915, uses of diuretics 348, Generalized, edema 161, epilepsy 935, Generation of, action potential 925, in nerve fiber 779, bronchioles 674, Genesis of tetanus, and tetanus curves 183f, curves 182, Genetic, disorders 14, classification of 14, mutation 14, , transcription 394, variation 14, Geniculate body 1014, Geniculocalcarine, fibers 991, tract 991, Genu 853, GERD 273, Germ hill or cumulus oophorus 483, Germinal, epithelium 476, ridges 476, Gestation period 502, Gh insensitivity 386, Gh secretion, regulation of 379, 380f, Ghrelin 286, 860, GI hormones 238, Giant, cells 815, 885, ganglion cells 970, phagocytic multinucleated cells 411, Giddiness 502, Gigantism 377, 379, 384, causes of 384, Gland, adrenal 425f, Glands of, skin 356, small intestine 261, stomach 231, classification of 231, Glandular, fever 147, 157, tissues 510, Glans penis 466, Glanzmann’s thrombasthenia 126, Glaucoma 972, 975, causes of 976, treatment for 976, Glial, cell line-derived neurotrophic factor, 763, cells 773, Glicentin 285, Globin 78, Globin, formation of 80, Globosus nucleus 868, Glomerular, blood flow, regulation of 311, capillaries 313, capillary, membrane 316, pressure 317, 318, filtrate 316, filtration 316, 324, rate 311, 316, 318, 349, mesangial 309, cells 309, , Glomerulonephritis 334, Glomerulotubular balance 321, Glomus cells 593, Glossopharyngeal nerve fibers 1025, Glucagon 284, 418, actions of 418, like polypeptide-1 285, like polypeptide-2 285, secretion, regulation of 419, Glucocorticoids 408, 426, administration of 662, binding globulin 426, Gluconeogenesis 416, Glucose 284, 334, absorption of 288, buffer system 421, dependent insulinotropic hormone, 284, transporter 323, 416, Glucostatic mechanism 859, 859f, Glucostats or glucose receptors 859, Glucosuria 423, 501, Glutamate 867, 979, or aspartate 867, Glutamic acid 332, Glutaminase 332, Glutamine 332, Gluten-sensitive enteropathy 265, Glycine 252, Glycocholate 252, Glycocholic acid 252, Glycogenesis 416, Glycogenolysis 416, Glycolysis 197, Glycolytic pathway 197, Glycoproteins 6, 122, Glycosuria 334, Goblet cells 261, Goiter 397, in hypothyroidism 397, Goitrogens 397, Goldblatt hypertension 615, Goldmann perimeter 988, Golgi, apparatus 8, 9f, 761, cells 865, 866, tendon apparatus 911f, tendon organ 911, type I neurons 760, 804, type II neurons 760, 805, Gonadal steroid-binding globulin 462, Gonadotropes 376, Gonadotropic hormones 377, Gonadotropin-releasing hormone 377,, 461f, Gonadotropins 377, Gonads 455
Page 1077 :
1056 Essentials of Medical Physiology, Gonorrheal vaginitis 478, Good cholesterol 295, Goormaghtigh cells 309, Gorilla face 384, Gower tract 810, G-protein coupled, oxytocin receptor 384, receptor 1026, Graafian follicle 380, 484, 484f, 492, Graded potential 193, 193t, 767, Graded potentials, different 193, Gram-negative bacteria 661, Grand mal 935, Grand mal, causes of 936, Granit dominator-modulator theory 1000, Granular, cells 310, layer 866, pneumocytes 675, Granule cells 866, Granules 969, Granulocytes 97, Granulocytopenia 99, Granulocytosis 99, Granulosa cells 483, 485, Granulosa cells, changes in 483, Granulose cells 476, Granzymes 10, Graphical registration 551, Graves’ disease 120, 395, Graveyard of rbcs 67, Gravindex test 509, Gravitational force 740, Gravity 575, 618, 680, Gray matter of, cerebellum 865, spinal cord 804, Graying of vision 740, Grayout 740, Greater, circulation 524, curvature 230, Growth, factors 16, hormone 377, 408, 460, 461f, actions of 377, inhibiting hormone 285, 377, 420, receptor 379, releasing hormone 377, 793, releasing polypeptide 377, secretagogue 379, of ductile system 510, of glandular tissue 510, plate 409, Guanosine, diphosphate 313f, 373, triphosphate 313f, , Guillain-Barré syndrome 65, Gustatory sensation 1024, Gutter 201, , H, H substance 647, Hagen-poiseuille equation 598, Hair, cells 921, 922, 1013, of vestibular apparatus 922f, distribution 478, follicle 356, Hairpin bend 307, Haldane effect 715, Haldane effect, causes for 715, Haldane-priestely tube 704, Half-life of hormones 370, Hallucination 935, Hamburger phenomenon 714, Hammer 1008, Hamulus 1010, Haploid 459, 484, 498, cells 13, number of chromosomes 459, or half number of chromosomes 459, Harmful stimuli 796, Harrison sulcus 414, Harsh blowing sound 550, Hartridge polychromatic theory 1001, Hashimoto’s thyroiditis 119, 396, Haustra 266, Haversian, canal 410, lamellae 410, systems 410, Hazards of blood transfusion 146, HCG, actions of 506, antiserum 509, HCS, actions of 506, Head 471, or capitulum 1008, portion 5, of myosin molecule 172, Headache 741, Health benefits of dietary fiber 289, Hearing 1022, Heart 441, 446, 519, 601, actions of 522, attack 297, block 565, 590, disease 295, failure 654, 662, 663, acute 662, causes of 662, compensated 663, , rate 392, 557, 575, 587, 594f, 666,, 821, 931, decreases 799, regulation of 588, 858, variability 557, re-excitation of 568, sounds 544, 545t, description of 544, different 544, importance of 544, Heartbeat 600, Heartburn 240, Heart-lung preparation 582, 583f, Heat, balance 360, cramps 747, exhaustion 747, gain, center 361, 858, or heat production in body 360, loss, center 361, 858, from body 361, prevention of 361, 362, 746, of activation 199, of activity 360, of metabolism 360, of relaxation 199, of shortening 199, production 255, 746, prevention of 361, promotion of 362, rigor 183, Heatstroke 747, 748, Heidenhain pouch 235, Helicobacter pylori 239, Helicotrema 1010, 1011, Helium dilution technique 694, Helmholtz trichromatic theory 1000, Hematemesis 240, Hematinic principle 76, Hematocrit value 59, 149, Hematoma 412, Hematospermia 472, Hematuria 334, 335, 337, Heme 78, 80, Heme iron 82, Hemianesthesia 854, Hemianopia 854, 991, Hemiballismus 883, Hemidesmosome 25, Hemihyperesthesia 854, Hemiplegia 837t, Hemisection of spinal cord 823, Hemodromography 599, Hemodynamics 595, Hemofilter 346
Page 1078 :
Index 1057, Hemoglobin 44, 77, 80, 81, 335, abnormal 78, C 78, content 653, derivatives, abnormal 79, destruction of 81, 152, dissociation curve 713, E 78, in blood 353, in thalassemia and related, disorders 79, M 78, S 78, SS disease 91, Hemoglobinopathies 78, Hemoglobinuria 334, 335, Hemolysins 96, Hemolysis 95, 150, and fragility of red blood cells 95, Hemolytic, anemia 90, disease of fetus and newborn 143, function 256, jaundice 258, 335, transfusion reaction 142, Hemophilia 136, causes of 136, treatment for 136, Hemopoietic, function 232, 233, 255, 262, 263,, 302, growth factors 75, stem cells 21, Hemorrhage 651, acute 90, 652, 659, compensatory effects of 651, definition of 651, delayed compensatory effects of, 653, or blood loss 150, to premature detachment of placenta, 651, Hemorrhagic, anemia 90, shock 659, spots 136, stroke 637, Hemosiderin 147, Hemostasis 124, 127, Hemostasis, definition of 127, Hemothorax 674, Henderson cardiometer 541, 542, Henderson-Hasselbalch equation 43, Heparin 104, 450, actions of 450, therapy 136, Heparinase 133, , Hepatic 258, artery 250, circulation 639, lobes 249, lobule 250f, lobules 249, plates 249, sinusoids 251, stage 71, vein 251, Hepatitis 258, 259, Hepatocellular 258, Hepatocytes plates 249, Heptapeptide 310, Hereditary, chorea 883, trait 80, Hering nerve 592, 593, Hering’s theory of opposite colors 1001, Hering-Breuer inflation reflex 719, 719f, Hering-Breuer reflex 719, Hermaphroditism 455, Herpes 147, Heteronymous hemianopia 992, Hexapeptide 310, Hief sensory nucleus 812, High, altitude 737, and space physiology 737, atmospheric pressure 728, barometric pressures 69, 743, concentration of inorganic iodides 398, density lipoprotein 295, or hot temperature 183, pressure bed 314, Highly alkaline 242, High-molecular-weight kinogen 451, See HMW kinogen, High-threshold substances 321, High-tone deafness 1021, Hirschsprung disease 269, Histamine 104, 450, 611, 791, Histamine test 239, Histamine, actions of 450, Histotoxic hypoxia 727, 728, Histotoxic hypoxia, causes for 727, Hodgkin disease 93, 472, Hogben test 508, Holger nielsen method 750, Hollow back 414, Holmgren colored wool 1003, Homeostasis 38, 51, Homeothermic 178, animals 359, Homogeneous, translucent zone 352, hemianopia 992, , Honey 421, Honeycomb-like structure 249, Horizontal semicircular canal 924, Hormonal, action 372, receptors 372f, Hormone 313f, adrenocorticotropic 380, A-melanocyte-stimulating 395, 432, receptors 350, 372, receptors 372, regulation of 372, Β-melanocyte-stimulating 432, Hormones 367-371, 511, 857, and neurotransmitters 209, decrease blood pressure 610, 611, depending upon chemical nature,, classification of 371t, inhibiting, gastric motility and emptying 275, pancreatic secretion 247, involved in regulation 488, of arterial blood pressure 611t, necessary for spermatogenesis 460t, of adrenal, cortex 426, medulla 439, of anterior pituitary 380, 381, of thyroid gland 388, Hormones, effects of 407, 408, anti-insulin 421, chemistry of 371, on blood, calcium level 407f, phosphate level 408f, regulating tubular reabsorption 321t, secreted by, anterior pituitary 377, gonads 370t, hypothalamus 377, kidneys 302, major endocrine glands 369t, other organs 370t, testes 461, stimulating pancreatic secretion 246, Hormone-secreting cells 281, Horner syndrome 998, Horny layer 351, Houssay animal 417, Howell-Jolly bodies 70, Human 247, 264, Chorionic, gonadotropin 464, 506, 508, somatomammotropin 506, leukocyte antigen system 119, milk 244, sperm 471f
Page 1080 :
Index 1059, Hypoxia 68, 486, 649, 725, 730, delayed effects of 728, effects of 728, 738, treatment for 728, types of 727t, Hypoxic hypoxia 726, 727, Hypoxic hypoxia, causes for 726, Hysterectomy 494, , I, I band 171, I cells 284, 308, Ice cubes 748, Idiopathic, non-toxic goiter 397, parkinsonism 882, thrombocytopenic purpura 137, Idioventricular rhythm 527, 566, Ileocecal valve 261, Ileum 283, and colon 286, Iliac crests 951, Image forming mechanism 978, Imaginary equilateral triangle 552, Imaging technique 581, Immature erythrocytes 75, Immediate compensatory effects of, hemorrhage 652, Immune, deficiency diseases 118, system, effects on 742, Immunity 107, Immunity, definition and types of 107, Immunization 116, Immunoelectrophoretic method 62, Immunogenicity 110, Immunological, defense system 675, hypersensitive 120, reactions 120, test for pregnancy 509f, tests 509, for pregnancy, advantages of 509, Immunosuppressive effects 432, Impedance matching 1017, Implantation 499, of ovum 515, Impotence 393, Impulse transmission 780, Inactivation of, hormones and drugs 256, neurotransmitter 789, Inattentive brain or mind 929, Inborn, or acquired reflexes 796, reflexes 796, , Incisura angularis 230, Incompetence 550, of atrioventricular valves 550, of semilunar valves 550, Incomplete, heart block 566, transection of spinal cord 822, Increase in, pulmonary blood flow during, inspiration 680f, RBC count 68, size of RBC 85, Increases muscle tone 872, Increasing, amino acid transport cell, membrane 378, ribonucleic acid 378, transcription of DNA to RNA 378, Incus 1008, Index, finger 624, for fragility 96, Indicator dilution method 52, 578, Indifferent electrode 553, Indigestion and hypochlorhydria 502, Indirect, corticospinal tract 817, inhibition 783, light reflex 994, method of, capillary pressure 620, venous 618, method to arterial blood pressure 612, spinocerebellar tract 810, Infant hercules 438, Infantile glaucoma 976, Infatigability 769, Infectious agents 120, Inferior, Cervical, ganglion 955, sympathetic nerve 591, colliculus 845, 1014, oblique 974, 975f, muscles 974, olivary nucleus 820, 866, peduncles 868, rectus 974, 975f, salivatory nuclei 844, thalamic peduncle or radiation 850, vena cava 520, 583f, 648, 650f, Infertility 472, 496, definition of 496, in females 496, causes of 496, in males 496, causes of 496, , Inflammation of air passage 735, Infranodal block 566, Infrared rays 999, Infrequent delta waves 932, Inguinal canal 463, Inhalants 120, Inhibin 460, Inhibit action of aldosterone 349, Inhibitors of platelets 125, Inhibitory, centers for micturition 343, function 783, hormones 857, neurotransmitters 789, 789t, postsynaptic potential 789, 911, Initial, depolarization 525, heat 199, rapid repolarization 526f, repolarization 526, stage of intestinal phase 238, ventricular complex 554, Injury, by reperfusion 659, degrees of 770, to blood vessels 137, Innate immunity or non-specific, immunity 107, Inner, bony part 1008, hair cells 1011, layer or tunica interna 969, medulla 303, mucus layer 231, 475, nuclear layer 970, phalangeal cells 1011, pillar cells–rods of corti 1011, plexiform layer 970, segment 979, 980, tunnel 1012, visceral pericardium 521, Inorganic substances 52, Inositol triphosphate 374, Inotropic, action 522, effect 441, Insensible perspiration, method 361, Inside-out patch 193, Insomnia 933, 934, Inspiration active process 682, Inspiratory, capacity 691, 691f, 693f, center 716, muscles 682, muscles, accessory 683, neurons 717
Page 1081 :
1060 Essentials of Medical Physiology, ramp 717, 718, signals 718, reserve volume 691, 691f, 693f, Inspired air 703, composition of 703, definition of 703, Instantaneous mean vector 558, 558f, degree of 559, different limb leads, degree of 559, Instantaneous vector, degree of 559f, different leads, degree of 559f, Insulating capacity 762, Insulation function 295, Insulin 415, actions of 415, dependent diabetes mellitus 119, 421, protease or insulin-degrading, enzyme 415, receptor 417, secretagogues 424, secretion, regulation of 417, sensitizers 424, Integral, membrane proteins 22, proteins 5, Integration and regulation 874, Intensity 177, discrimination 990, Intention tremor 852, 877, Interatrial septum 520, Intercalated, cells 330 See I cells, disk 521, duct 224, Intercellular matrix 409, Interdigestive phase 236, 239, Interferons 116, Interleukins 116, Interlobar artery 312, Interlobular, artery 312, ducts 224, Intermediate, density lipoproteins 294, filament 12f, group 902, mass 847, normoblast 74, trapezoid fibers 1014, Intermediolateral nucleus 812, Internal, anal sphincter 220, arcuate fibers 813, capsule 818, 853, 991, capsule, definition of 853, carotid artery 634, , ear 1010, elastic lamina 523, environment or ‘milieu interieur’ 51, genitalia 456, granular layer 885, hemorrhage 651, hydrocephalus 953, jugular vein 634, limiting membrane 970, OS 475, respiration 673, structure of, axon 761, spinal cord 804, urethral sphincter 339, 340, Internalization 372, International normalized ratio 136, Interneuronal activity in, cerebellum 867t, Interneurons 796, Internuncial neurons 796, Interoceptors 775, 777f, Interpretation of arterial pulse, tracing 623, Interstitial cell, of leydig 457, stimulating 464, hormone 380, 460, 465f, Interstitial matrix 310, Intervals and segments of ECG 556, Interventional cardiology 581, Interventricular septum 520, of heart 558f, Intervertebral foramina 804, Intestinal, cancer 158, gland and villus 262f, glands 261, lipase 293, phase 237, 238, 239, 246, initial stage of 238, ulcer 262, villi 261, Intestine 286, 287, 293, 428, Intorsion 974, Intra-alveolar pressure 686, Intra-arterial pressure changes cardiac, cycle 536, 538f, Intra-atrial pressure curve 538, Intracellular, chemical mediators 368, edema 160, electrode 767, enzyme 373, hormonal mediator 373, potassium ions, importance of 189, Intracranial pressure 992, , Intrafusal, fibers 806, 888, 915, of muscle 833, muscle fibers 909, Intraglomerular mesangial cells 309, Intralaminar nuclei 847, 848f, Intralobular duct 224, 241, Intramural vessels 629, Intraocular, fluid 971, pressure 972, Intrapleural, fluid 674, pressure 674, 684, 685, cause for negativity of 685, space 674, Intrapulmonary pressure 686, Intrathoracic pressure 685, Intrauterine, contraceptive device 515, death 144, Intraventricular pressure 539, changes during cardiac cycle 539,, 540f, curve 539, Intravesical pressure 342, Intrinsic, ability 600, capacity 600, factor 233, of castle 75, 261, hemolytic anemia 91, muscles 973, muscles, innervation of 973, nerve supply 221, pathway for formation of prothrombin, activator 130, tracts 807, Inulin, clearance 335, space 53, Inverse, myotatic reflex 912, stretch reflex 911, Inversely proportional 575, 680, to elasticity of blood vessels 605, to resistance 597, Involuntary, movements 852, muscle 167, muscular activity 746, Involve negative feedback control 655, Iodide trapping 389, Iodide-chloride pump 390, Iodinase 397, Iodination of tyrosine 390, Iodine deficiency goiter 397
Page 1082 :
Index 1061, Iodopsin 983, Ion channel diseases 29, Ion channels 27, 28, Ionic balance 714, Ionic basis of, action potential 191, 207, 526, electrical activity in pacemaker 528, resting membrane potential 189, Ions 684, Ions, charge of 30, Iris 968, angle 968, sphincter 968, Iron 76, 78, absorption of 82, deficiency anemia 91, importance of 81, lung chamber 750, metabolism 77, 81, rich mitochondria 296, Irregular, astigmatism 1005, bowel habit causes 268, Irreversible stage 655, of circulatory shock 658f, Irritant receptors of lungs 720, Irritation of, nasal mucous 677, respiratory tract 677, Ischemia 137, 840, Ischemic stroke 637, Ishihara color charts 1003, Islets of langerhans 415, Isoagglutinin 140, Isoelectric, base 191, potential 191, Isometric, contraction 178, 535, 539, 542, 544, period 535, 628, muscular contraction 665, relaxation 536, 539, period 536, 543, 628, Isotonic, contraction 178, dehydration 55, fluid 55, simple muscle curve f, Isotropic 171, Isovolumetric, contraction 535, relaxation 536, Isthmus 474, IUCD, disadvantages of 515, , J, J point 557, J receptors of lungs 719, , Jacksonian epilepsy 936, Jacobson organ 1028, Jaundice 142, 254, 258, 334, Jejunum 282-284, Johann Christian Doppler 576, John braxton hicks 503, Jugular venous pulse tracing 627, Junctional adhesion molecules 22, Juvenile glaucoma 976, Juxtacrine messengers or local, hormones 367, Juxtaglomerular apparatus 309, 309f, Juxtaglomerular apparatus,, definition 309, Juxtaglomerular cells 310, Juxtallocortical structures 898, Juxtamedullary nephrons 305, , K, K cells 284, Kallidin 451, LMW kinogen, formation of 451, Kallikrein 451, Kallikreins, actions of 451, Kallmann syndrome 862, Kaolin 135, Kearns-Sayre syndrome 15, Keratinocytes 352, Kernicterus 144, 211, 883, Ketoacids 47, 423, Ketogenic effect of glucocorticoids 431, Ketone bodies 335, Ketonuria 423, Ketosis 501, Kety and schmidt nitrous oxide, method 634, Kidney 32, 94, 301, 401, 402, 445,, 601, 652, artificial 346, different layers of 302, effects on 728, 742, functional anatomy of 302, plays 330, Kinesin 36, 37f, Kinesthetic sensation or kinesthesia 829, Kinin system 450, Kinin-Kallikrein system 450, Kinins 450, actions of 451, formation of 451, Kinocelium 922, 1011, Kirchhoff’s law of voltage 560, Kluver-Bucy syndrome 894, Koilonychias 91, Kölliker-fuse nucleus 718, Krebs cycle 198, , Kupffer cells 67, 249, 256, Kupperman test 508, Kussmaul, breathing 423, sign 628, occurs 628, , L, L cells 418, in ileum and colon 285, Labial glands 224, Labor 448, contractions 503, Labyrinth 919, 921f, Labyrinthectomy, effect of 927, Labyrinthine 918, Lacis cells 309, Lack of, concentration 891, pancreatic lipase 248, Lacrimal, ducts 967, gland and tear 967, sac 967, secretion 932, Lactase 287, Lactation 511, on menstrual cycle, effect of 511, Lactic acid 46, Lactotropes 376, Lacunae 410, Lambert-Eaton, myasthenic syndrome 65, syndrome 213, Lamellar bodies 684, Lamina, around central canal 806, cribrosa 967, in lateral gray horn 806, propria 220, reticularis 1012, reticularis 1012, Laminae 806, in anterior gray horn 806, in posterior gray horn 806, Landsteiner law 139, Laparoscope 515, Large, intestine 266, functional anatomy of 266, lymphocytes 98, Largest sense organ 354, Laron dwarfism 386, Laryngeal stridor 403, Laryngospasm 403, Laser coronary angioplasty 581, 633
Page 1083 :
1062 Essentials of Medical Physiology, Last rapid filling phase 534, 536, or presystole 534, Latch-Bridge mechanism 208, Late, dumping 275, normoblast 74, Latent, autoimmune diabetes in adults 422, period 178, 190, causes of 179, tetany 403, Lateral, column 809, 811, corticospinal tract 817, decubitus 546, funiculus 806, geniculate body 989, 991, 992, group 901, intercellular space 322, mass of nuclei 848, 848f, motor systems 835, rectus 974, 975, 975f, reticular nucleus 812, spinothalamic tract 809, sulcus 886, surface of cerebral cortex 888f, ventricles 950, vestibular nucleus 813, 819, vestibulospinal tract 819, white column 806, 810, 812, 820, of spinal cord 820, Latex particles, agglutination of 509, Laurence-moon-biedl syndrome 862, Law of, Laplace 343, projection 779, Law, Bell-Magendie 785, Law, Newton 580, Law, Starling 184, of intestine 277, Laxative action 253, 255, Layer of, cerebral cortex 885, cones 969, dermis 353, epidermis 351, nerve fibers 970, pigment epithelium 969, respiratory membrane 705, 706t, retina 970f, rods and 969, skin 351, wall of heart 520, Leak channels 189, Leber’s hereditary optic, neuropathy 15, Lectin pathway 114, , Left, arm 559, atrial dilatation or hypertrophy 554, atrium 520, 650f,, axis deviation 561, heart catheterization 580, nasal hemianopia 993f, or right nasal hemianopia 992, side of heart 520, sided heart failure 663, superior intercostal veins 678, ventricle 520, 650f, ventricular, contraction or vis a tergo 618, pressure, directly proportional to, 618, Lemniscus 830, Length, and extent of loop of henle 307, force curve 185, of spinal cord 803, tension, curve 185, 187f, relationship 185, plasticity 208, Lens 972, biconvex 1005, 1006, old age, changes in 973, substance 973, Lenticular, nucleus 879, process 1008, Leptin 395, 450, actions of 450, receptor 860, Lesion of, area 4, effect 889, broca area, effect 890, effect 1015, internal capsule, effect 853, lateral fibers in left side of optic, chiasma 993f, left optic nerve 993f, optic pathway, effects 993f, prefrontal cortex, effect 891, right optic nerve 993f, supplementary motor area, effect 891, visual cortex, effects 992, Lesser, circulation 524, curvature 230, Lethargy 393, Leukemia 99, Leukocytes 676, Leukocytosis 99, Leukopenia 99, Leukopoiesis 105, 105f, , Leukotrienes 449, Levels of visual pathway 991, Levodopa 883, Lewis, blood group 144, triple response 647, LH, actions of 380, Liberation of energy 197, Liddle’s syndrome 37, Life-protecting hormone 430, Life-saving, glands 425, hormone 426, procedure 146, Lifespan, and fate of platelets 125, of red blood cells 67, of red blood cells 67, of WBCs 98t, of white blood cells 101, Life-threatening 423, 654, reactions 337, Ligand-gated channels 28, Light, adaptation 984, adaptation, causes of 985, band 171, energy 982, rays, effects of 739, reflex 798, 994, 995f, Limbic, lobe 898, system 898, system, connections of 899, Limbus 898, 968, 972, Lingual, lipase 226, 293, mucus glands 224, Lipid, absorption of 292, 293, digestion of 243, 292, 293, 294t, in diet 292, layer 28f, layers of cell membrane 5, metabolism of 292, 296f, 501, 507, of cell membrane 5f, profile 297, Lipocytes 295, Lipolytic 226, enzyme 262, 293, enzyme in succus entericus 293, enzymes in pancreatic juice 293, Lipoprotein lipase 294, Lipoproteins 294, classification of 294, importance of 295, Lipostatic mechanism 859
Page 1084 :
Index 1063, Lipoxins 449, Lippes loop 515, List of, ascending tracts of spinal cord 807t, descending tracts of spinal, cord 814t, Lithium battery 569, Liver 249, 301, disease affecting secretion of bile, 248, failure 883, fats, action on 392, Load, effect of 184, Lobar pneumonia and lobular, pneumonia 734, Lobes of cerebral cortex 886, 886f, Lobules of testis 456, Lobulus, ansiformis 864, paramedianus 864, Local, anesthesia 515, autoregulation 638, depolarization or excitatory, junctional potential 208, factors determining arterial blood, pressure 604t, factors, mechanical factors 604, hormones 370t, 747, classification of 447, produced in blood 450, synthesized in tissues 447, 449, mechanism for regulation of blood, pressure 611, myenteric reflex 237, potential 766, 767, regulation of blood flow–, autoregulation 600, static reflexes 916, substances involved in regulation of, arterial blood pressure 612t, vasoconstrictors 611, vasodilators 611, Localization of sound 1021, Localization–homunculus 889, 892, Localized epilepsy 936, Localized epilepsy, causes of 936, Lockjaw disease 183, Loewi experiment 787, Long bones 71, refractory period 531, in cardiac muscle 187, 531, tracts 807, Longer process of nerve cell 761, Longitudinal section of, kidney 303f, neuromuscular junction 200f, , Long-term, contraceptives 514, regulation 608, Loop, diuretics 349, of henle 306, 326, Loss of, coma 733, consciousness 733, 741, crude touch 809, reflexes 821, sensations 821, 852, temperature regulating capacity 747, vision 741, voluntary movement 821, Loud, or accentuated first heart sound 545, or accentuated second heart sound, 546, snoring 934, sound 550, Loudness or intensity 1020, Loudspeaker 548, Low, barometric pressure 737, density lipoprotein 295, oxygen tension in inspired air 726, pressure, bed 314, 679, system 679, resistance 660, threshold 980, voltage fluctuations 932, Lower, AV nodal rhythm 554, cervical segments 820, costal series 683, extremities 813, fields 987, lumbar segments 810, motor neuron 836, 817, lesion 802, 825, parts of body 813, respiratory tracts 674, Low-molecular-weight kinogen 451 See, LMW kinogen, Lown-Ganong-Levin syndrome 568, Low-threshold substances 321, L-tubules or sarcoplasmic reticulum 174, Lubrication, activity 267, function 255, Ludwig jacobson 1028, Lumbar, ganglia 955, puncture 951, puncture, posture of body for 951, , Lumbosacral vertebral defects 345, Lumirhodopsin 982, Lung, cancer 158, capacities 691, own defenses 676, volumes 690, and capacities 691f, in vital capacity 696, Lungs 151, 301, collapse of 734, collapsing tendency of 684, Luteal phase 485, 489, Luteinization 485, Luteinizing, hormone 380, 460, 464, 489f, 490, releasing hormone 465f, Luteolysis 448, Lutinizing hormone 461f, Lymph 158, capillaries 155, composition of 157f, 158, drainage 156f, formation of 158, node 156, 156f, swelling, causes for 157, vessels 155, Lymphatic, system 155, and lymph 155, organization of 155, vessels to lymph node 156, Lymphedema 161, Lymphocytes 72f, 98, 105, 107, 676, Lymphocytopenia 101, Lymphocytosis 101, Lymphoid organs 71, Lymphomas 158, Lysin 418, Lysis 114, of clot 487, of coagulum 468, Lysosomal enzymes 9, Lysosomes 9, Lysozyme 354, 967, Lysylbradykinin 451, , M, Machinery murmur 550, Macrocytes 70, Macrocytic, hypochromic anemia 89, normochromic anemia 89, Macrogenitosomia praecox 438, Macromolecules, degradation of 9, Macrophage system 151
Page 1085 :
1064 Essentials of Medical Physiology, Macrophages 110, 151, Macula 920, 922, adherens 25, densa 309, 314, 317, in otolith organ 923f, in saccule 922, in utricle 922, lutea 971, Macular, representation 991, sparing 992, Magenstrasse 274, Magnetic resonance imaging 635, Maintenance heat 199, Maintenance of, acid-base balance 302, cell polarity 23, electrolyte balance 302, milk secretion or galactopoiesis 511, muscle tone 187, pH in gastrointestinal tract 255, pregnancy 485, pressure in biliary system 256, shape and size of cell 6, sperm motility 468, spermatogenesis 460, water balance 40f, 55, 302, 676, Major, basic protein 104, calyces 303, calyx 308, complexes in ECG 553, components of limbic system 900f, endocrine glands 369f, salivary glands 223, 224f, Malabsorption 265, syndrome 265, Male, condom 514, gamete 470, reproductive system 455, 456f, urethra 339, urinary bladder and urethra 340f, Malignant, enlargement 469, hypertension 614, Malleus 1008, Malpighian corpuscle 153, 304, Maltase 226, 287, Maltose 226, Mamillotegmental tract 856, Mamillothalamic tract 856, Mammalian heart 527, Mammary glands 500, and lactation 510, Mammary glandsm, development, of 510, , Manifestations of, circulatory shock 654, hypertension 615, hypovolemic shock 659, osteoporosis 413, Manometer 623, Manual methods of artificial, respiration 749, Manubrium 1008, sterni 683, Mapping of visual field 988, Marchi staining 895, Marey, law 592, reflex 592f, function 592, tambour 541, 627, Marginal, nucleus 805, 809, 810, 839, zone nucleus or border nucleus 805, Marker substances 53, Marrow cavity 410, Masculine features 433, Mask-like face 881, Mass, peristalsis 278, reflex 822, Massive blood transfusion 147, Mast cells 104, 133, Master gland 376, Mastication 270, Mastication, control of 270, Matching and cross-matching 141, Maternal, changes during pregnancy 500, hormones 503, Matrix 409, GLA protein 410, Maturation factors 75, Matured erythrocyte 74, Maturity onset diabetes 422, Maximum and minimum pressure in, aorta 540, atria 538, ventricles 539, Maximum, breathing capacity 697, ventilation volume 697, Mcardle disease 213, Mean, Arterial, blood pressure 603, pressure 600, corpuscular, hemoglobin 87, 88, hemoglobin concentration 87, 88, volume 87, 88, , QRS vector 559, velocity of blood flow in different, vessels 599, volume of blood flow 595, Measurement of, arterial blood pressure 612, blood volume 149, body fluid volume 52, capillary pressure 620, cardiac, output 576, output by direct methods 576, output by indirect methods 576, output by using carbon dioxide 578, output by using oxygen, consumption 577, cerebral blood flow 634, circulation time 599, compliance 687, coronary blood flow 630, dead space 702f, nitrogen washout method 701, dynamic compliance 688, end-diastolic volume 535, 536, extracellular fluid volume 53, functional residual capacity and, residual volume 694, glomerular filtration rate 335, interstitial fluid volume 54, intracellular fluid volume 54, lung volumes and capacities 692, plasma volume 54, pulmonary blood flow 679, renal, blood flow 313, 336, plasma flow 336, static compliance 687, total body water 53, venous pressure 618, Meat 290, Mechanical, cushion 295, factors of blood flow 644, flowmeter 576, fragility 95, function 232, 263, methods of artificial respiration 750, Mechanically gated channels 28, Mechanics of respiration 682, Mechanism for, accommodation 995, action of, antibodies 114, basophils 104, bicarbonate buffer system 44, corticocerebellum 875, cytotoxic T cells 111
Page 1086 :
Index 1065, eosinophils 102, heparin 133, 134t, homeostatic system 39, immunoglobulins 115f, IUCD 515, neutrophils 102, vestibulocerebellum 870, active transport 31, aldosterone escape 427, bicarbonate secretion 244, conduction of action potential 768, enterogastric reflex 275, exocytosis 36, formation of dilute urine 328f, glomerulotubular balance 321, hearing 1016, hormonal action 372, innate immunity 107, 108t, inverse stretch reflex 912, labor 503, lysosomal function 9, muscle pump 575f, pancreatic secretion 244, phagocytosis 34, phosphate buffer system 44, pinocytosis 34, reabsorption 320, receptor-mediated endocytosis 35, referred pain 840, regulation of food intake 859, saltatory conduction 768, sleep 933, temperature regulation 361, transcytosis 36, vomiting 276, Mechanoreceptors 775, Mechanotransduction 924, Medial, forebrain bundle 856, group 902, lemniscus 832, 1025, longitudinal fasciculus 818, mass of nuclei 848, motor systems 835, or internal rectus 974, rectus 975, 975f, surface of cerebral cortex 889f, Mediastinum testis 456, Medical termination of pregnancy, abortion 515, Medicolegal importance of rigor, mortis 184, Medium of exchange 951, Medulla 156, 476, adrenal 425, 439, oblongata 796, 844, , Medullary, centers 716, 717t, gradient 325, hyperosmolarity 325, or malpighian pyramids 303, reticulospinal fibers 819t, Megalin 391, Megaloblast 73, Megaloblastic anemia 76, 92f, 93, Meibomian glands 966, Meissner nerve plexus 221, 231, Melanin 353, 354, 969, Melanocytes 352, 353, Melatonin 444, Melatonin, actions of 444, Membrana granulosa 483, Membrane proteins 22, Membranous, bones 71, cochlea 1011, disks 979, labyrinth 920, spiral lamina 1010, urethra 340, Menarche 475, 482, 510, Menopause 475, 482, 494, Menopause, cause for 494, Menorrhagia 491, Menses 486, Menstrual, bleeding 490, cycle 482, definition of 482, duration of 482, regulation of 488, period 486, phase 486, 490, phase, changes in endometrium, during 486, symptoms 490, Menstruation or menstrual bleeding 486, Menstruation, abnormal 490, 491, Mental retardation 392, 393, Mercury manometer 582, 612, Mesangeal cells 446, Mesencephalon 758, Mesenteric, blood flow, regulation of 638, circulation 638, ganglia 221, Mesoblastic stage 71, Mesovarium 476, Messenger rna 16, Meta-adrenaline 440, Metabolic, acidosis 46, 332, acidosis, causes of 46, , activities 360, 746, alkalosis 47, 332, changes 501, disorders 731, factors 631, function 255, reactions 51, 362, theory 601, Metabolism 94, 400, 405, 415, 418, 478, in aerobic and anaerobic, exercises 665, of calcium 8, of carbohydrates 288, of catecholamines 440, 440f, of lipids 296, of pancreatic polypeptide 420, of proteins 291, of somatostatin 420, of thyroid hormones 389, Metabotropic glutamate receptor 1027, Metanoradrenaline 440, Metaplasia 20, Metarhodopsin I 982, Metarhodopsin II 982, Methacholine 959, Methemoglobin 79, 727, Methemoglobinemia 79, Methemoglobinemia, causes of 80, Metheonine 43, Method of, examining radial pulse 624, recording, cystometrogram 342, EEG 929, 985, Method to plot oxygen-hemoglobin, dissociation curve 712, Methods of, artificial respiration 749, gastric analysis 239, recording arterial pulse 623, Methods to record venous pulse 627, Methods to study cortical connections, and functions 895, Methoxylation 440, Methyl mercaptan 1029, Methylation 440, Metrorrhagia 491, Meynert decussation 845, Micelles 253, Microcirculation 640, Microcytes 70, Microcytic hypochromic anemia 89, Microfilament of ectoplasm 12f, Microfilaments 12, Microglia 774, Microphone 548, Micropipette 316
Page 1087 :
1066 Essentials of Medical Physiology, Microprocessor-driven air pump 613, Micropuncture technique 319, Microtubules 12, 12f, 123, Microvilli 261, Micturition 339, reflex 343, syncope 660, Midbrain 758, 796, 845, disorders of 929, preparation 907, reflexes 796, Middle, AV nodal rhythm 554, cervical ganglion 955, ear 1008, finger 624, layer 968, peduncles 868, Midget ganglion cells 970. 990, Midline, nuclei 847, nucleus 848f, Midpiece 472, Migrating, motor complex 278, myoelectric complex 278, Mild, and moderate dehydration 56, dehydration 55, depolarization 925, 1019, exercise 666, hemorrhage 652, hypothermia 363, symptoms like headache and, nausea 733, Milk 290, digestion of 243, ejection 511, reflex 382, 383f, 511, reflex or milk let-down reflex 511, secretion 511, or lactogenesis 511, Mineral metabolism 431, 501, Mineralocorticoids 426, Minerals, absorption of 264, Miniature endplate potential,, development of 202, Minipills or micropills 514, Minor, calyx 303, 308, salivary glands 224, Minute, ventilation 700, volume 573, Miosis 998, Mismatched blood transfusion 146, Mitochondria 200, 761, , Mitochondria, activity of 391, Mitochondrial, DNA disorders 15, myopathy 213, uncoupling protein 1 296, Mitochondrion 10, Mitral, area 5437, valve 522, Mixed, apnea 725, glands 224, Mixing movements 277, MNS blood groups 145, MO cells 286, Model of cell membrane 4, Moderate, dehydration 55, exercise 666, hypothermia 363, Modiolus 1010, Modulators 1000, Modulatory neuron 784, Mole and Osmole 54, Molecular basis of, muscular contraction 194, smooth muscle contraction 208,, 208f, Molecular, motors 36, 197, or plexiform layer 865, 885, Monoamine oxidase 440, Monochromatism 1002, Monocular vision 987, Monocytes 72f, 98, 104, Monocytopenia 101, Monocytosis 101, Monophasic action potential 192, in crushed axon 193f, Monophosphate 373f, Monoplegia 837t, Monosaccharides 287, Monosodium glutamate 1026, Monosomy 15, Monosynaptic reflex 796, 910, Monounsaturated fats 292, Monro-Kellie doctrine 636, Moral and social sense 891, Morphology of, red blood cells 66, white blood cells 97, Mossy fibers 867, Motilin 286, Motion sickness 927, cause of 927, definition of 927, prevention of 928, , Motor, activities of body 832, activity, control of 880, endplate 200, nerve, fibers to heart 589, supply 910, to nuclear bag fiber 910, neuron diseases 763, neuron lesions, effects of 837, or efferent neurons 760, pathways, classification of 835, unit 203, unit, definition 203, Mountain sickness 739, Mountain sickness, treatment of 739, Mouth 287, 290, 293, Mouth and salivary glands 223, Mouth-to-mouth method 749, Movement, disorders during sleep 934, of eyeball during nystagmus 925, Movements of, eyeballs 846, 923, eyes 845, gastrointestinal tract 270, head 845, and body 923, intestine 639, large intestine 278, limbs 845, lungs 683, mastication 270, right eye 975f, shoulder 844, small intestine 277, 277f, stomach 273, thoracic cage 683, tongue 844, trunk 845, villi 278, Mucosa 339, Mucous membrane 93, reflexes 797, Mucus 233, 675, glands 224, layer 220, 267, plug 500, Müeller’s, cells 970, doctrine 776, experiment 619, law 776, maneuver 619, maneuver, effects of 619, supporting fibers 970
Page 1088 :
Index 1067, Müllerian, duct 462, inhibiting substance 458, regression factor 458, 462, Multifactorial genetic disorders 14, Multigated acquisition–muga scan 535, Multilocular 295, Multinucleated cells 13, Multiple, sclerosis 826, sclerosis, cause of 826, stimuli, effects of 180, Multipolar neurons 759, Multiunit smooth muscle fibers 206, Multiunit smooth muscle fibers,, distribution of 206, Mumps 229, 458, Murmur to anemia 550, Murmur, causes of 549, Murmur, classification of 550, Murmuring sound 613, Muscarinic receptors 959, Muscle, cells 169, 171f, composition of 175, fiber 169, 522, mass 169, power of 214, spasm 182, spindle 908, 909f, receptor organ for stretch reflex 910, tissue 3, tone 187, 819, 870, 913, 932, control of 846, 880, definition 187, development of 913, 914f, regulation of 914, Muscles 431, and movements of mastication 270, classification of 167, of eyeball 973, of mastication 270, of respiration 682, part in ocular movements 975t, Muscular, activity 360, contraction 188, 195, 195, contraction, changes in sarcomere, 196, dystrophy 211, exercise 69, factor 545, hypertrophy 20, layer 220, 230, 266, spasm 403, weakness 427, Muscularis mucosa 220, , Musculoskeletal system, effects on 742, Myasthenia gravis 64, 119, 203, 211, 212, Myelin sheath 762, chemistry of 762, formation of 762, Myelinated nerve fibers 762, 762f, 764,, 768f, Myelinogenesis 762, Myeloid stage 71, Myeloperoxidase 104, Myeloproliferative disorders 70, Myenteric nerve plexus 221, Myocardial, infarction 536, heart attack 632, ischemia 632, acute 556, and necrosis 632, stunning 632, tension 545, Myocardium 521, Myocytes 169, Myoepithelial cells 357, Myofibrils 170, 171f, 205, 521, Myofilaments 171, 205, Myogenic, response 314, theory 601, Myoglobin 78, 175, 659, Myometrium or middle muscular, layer 474, Myopathy 414, Myopia or short sightedness 1004, Myosin 36, 123, filaments 172, 172f, head binds with actin 195f, kinase 374, molecule 172, 173, Myotonia 212, Myxedema 396, Myxedema, causes for 396, , N, NADPH oxidase 102, Narcolepsy 862, 934, Narcotic effect of nitrogen 743, Nasal fields 987, Nasolacrimal duct 967, Nasopharynx 271, Natriuresis 609, Natural, detergent action 255, killer cell 115, peptide antibiotics 262, reflexes 796, Nausea 276, 502, , Near vision 986, Nebulin 173, Necessity of regulation of blood glucose, level 421, Neck, reflexes acting on eyes 918, righting reflexes acting on body 916, Necrosis 18, 632, Necrosis, causes for 18, Necrotic, endometrium 486, process 19, tissue 240, Negative, afterimage 1002, feedback 479, control 488, inhibition 784, mechanism 40, 40f, G 740, G, effects of 741, nitrogen balance 430, pressure breathing 585, sign, Babinski 799, signals, arrival of 18, supporting reflexes 917, Negatively charged substances 189, Nelson syndrome 436, Nemaline myopathy 213, Nemaline-rod myopathy 213, Neocerebellum 865, 872, Neocortex 885, Neonatal, and adult circulation 650f, circulation 649, respiration 649, Neostigmine 212, Neostriatum 879, Nephritis 337, Nephrogenic diabetes insipidus 329,, 387, Nephrons 303, 304, Nephrons, classification of 305, Nephrotic syndrome 334, Nerve, abducent 973, aortic 593, cell 759, body 760, body, changes in 772, destruction of 895, changes in 771, coverings of 761, deafness 1022, deafness, causes for 1022, fiber, action potential in 767f
Page 1089 :
1068 Essentials of Medical Physiology, degeneration and regeneration of, 771f, fibers 764, 765, 814, classification of 764, properties of 766, regeneration of 770, 772, used for voltage clamping 768, growth factor 763, impulse 766, impulse, action potential or 766, of emptying 341, organization of 761, regeneration 774, roots 803, supply 592, 593, 607, 608, of pancreas 241, of pavlov pouch 235, to baroreceptors and, chemoreceptors 592, to gastrointestinal tract 221, to golgi tendon organ 911, to heart 589f, to muscle spindle 909, 909f, to pancreas 242, to salivary glands 227, to urinary bladder 341, to urinary bladder and urethra 342f, to vestibular apparatus 922, Nervous, factors 209, 275, 321, 632, 636,, 638, 639, 643, 680, of blood flow 644, of pulmonary blood flow 680, mechanism 237, 716, for regulation of blood pressure, 605, regulation 264, of respiration 717f, system 502, 653, 739, 757, divisions of 757, organization of 758f, tissue 3, Net filtration pressure 317, Neural, basis of visual process 979, factor 257, Neurilemma 762, Neurilemmal sheath 762, Neurocrine or neural messengers 368, Neuroectodermal 376, Neuroendocrine, cells 281, reflexes 382, 383, 504, 511, Neurofibrils 761, Neurogenic, hypertension 614, shock 660, , Neuroglia 773, Neuroglial cells, classification of 773, in CNS 774f, Neuroglobin 78, Neuroglycopenic symptoms 424, Neurohormones 368, 376, Neurohypophysis 381, Neurokinins or tachykinins 791, Neuromodulators 791, actions of 792, chemistry of 792, vs neurotransmitters 791, Neuromuscular, blockers 202, hyperexcitability 403, 730, junction 200, definition 200, disorders of 203, in smooth muscle 208, system 94, transmission 201, 202f, transmission, definition 201, Neuron 759, 760f, Neuron, classification of 759, Neuronal activity in cerebellar cortex, and nuclei 867, Neurons, in gray, horn of spinal cord 805f, matter of spinal cord 804, matter, organization of 805, Α-motor 817, 888, β-motor 817, Neuropeptide Y 286, 860, Neurophysins 381, Neurotransmitter, definition of 787, depletion of 785, Neurotransmitters 368, 787, 788t, 789, classification of 787, involved in, functions of basal ganglia 881t, pain sensation 840, of analgesic pathway 841, of ANS 958, Neurotrophic factors 762, Neurotrophin-3 763, 762, Neurotrophins 763, Neutral fat 294, Neutralization of acids 267, Neutralizing action of pancreatic juice 244, Neutropenia 101, Neutrophil 72f, Neutrophilia 99, Neutrophils 97, 102, 676, Newborn babies 71, , Newly generated mediators 104, Newton’s third law of motion 580, Nickel 76, Nicotinamide adenine dinucleotide 79, Nictitating membrane 206, Night, blindness 985, blindness, causes of 985, terror 934, vision 980, Nightmare 934, Nigrostriatal pathway 882, Nissl, bodies 760, granules 760, Nitric oxide 791, Nitrite 335, Nitrogen, narcosis 743, washout method 694, washout technique 694, Nitrous oxide 634, Nociceptic stimuli 796, Nocturnal, enuresis 934, gastric analysis 239, micturition 344, Nodal extrasystole 567, Node of ranvier 762, Nodulus 863, Noisy flow 596, Nonadrenal actions of ACTH 433, Non-chromosomal DNA 14, Non-heme iron 82, Non-hemolytic transfusion reaction 142, Noninsulin-dependent diabetes, mellitus 422, Non-myelinated nerve fibers 761, 762f,, 764, 768f, Non-neural cells 773, Non-opioid neuromodulators 793t, Non-opioid peptides 792, Non-pitting edema 162, Non-pregnant uterus 383, Non-protein substance 8, Non-rapid eye movement sleep 932, 932t, Non-respiratory functions of respiratory, tract 675, Non-self antigens 109, Non-sensory impulses 811, Non-shivering thermogenesis 296, Non-striated muscle 167, Non-threshold substances 321, Non-toxic goiter 397, 397f, Non-vegetarian diet 287, Non-volatile acids 43, Noradrenaline 442, 606, 610, 790, 933
Page 1090 :
Index 1069, Noradrenaline, actions of 440, Normal, atmospheric pressure 728, blood, flow 639, flow to skin 646, glucose level 421, volume 148, body temperature 359, carbon dioxide dissociation curve 715, cardiac output curves 584, 585f, cardiogram or sinus rhythm 527, cerebral blood flow 634, chronaxie 177, coronary blood flow 630, count and variations 123, diastolic pressure 603, eye 998, function of central nervous system 393, hand 385f, heart rate 587, hemoglobin content 77, mean arterial pressure 603, oxygen-hemoglobin dissociation, curve 712, plasma levels of bilirubin 254, pulse pressure 603, RBC 92f, respiratory rate at different age 673, shunt level 679, systolic pressure 603, value and distribution of iron in, body 82, value of, capillary pressure 620, dead space 701, definitions and 603, different WBCs 99t, ESR 84, PCV 86, some important substances in, blood 59t, white blood cell count 99, Normocytic normochromic anemia 89, Normotopic arrhythmia 562, Nose clip 693, Nuclear, bag fiber 909, chain fiber 909, membrane 13, Nucleases 243, Nuclei 805, in anterior gray horn 806, in lateral gray horn 805, in posterior gray horn 805, of hypothalamus 855, 856f, 856t, of medullary reticular formation 902, , of midbrain reticular formation 902, of pontine reticular formation 902, Nucleolus 13, Nucleoplasm 13, Nucleosome 13, Nucleus 4, 12, 372, 760, ambiguous 717, Edinger-Westphal 957, 973, 995, emboli-formis 868, fastigi 868, globosus 868, gracilis 813, magnocellularis 845, of lateral lemniscus 1014, of tractus solitarius 607, in medulla and pons 589, parvocellularis 846, proprius 805, raphe magnus 841, reticularis 841, gigantocellularis 812, retroambiguous 717, Number of, muscle fibers in motor unit 203, stimulus, effect of 180, Nurse cells 458, Nutrition, deficiency anemia 91, to sperms 467, Nutritive function 60, 505, Nyctalopia 985, Nystagmus 877, 925, in pathological conditions 926, , O, Obesity 387, 421, 934, Obligatory reabsorption of water 328, Observations during examination of, pulse 624, Obstruction of reproductive ducts 496, Obstructive, apnea 724, jaundice 258, respiratory disease 699, Occipital lobe 894, areas and connections of 895t, connections of 895, Octapeptide 310, Ocular, movements 974, muscles 966, 973, muscles, innervation of 973, Oculomotor nerve 973, Oculosympathetic palsy 998, Odor, classification of 1029, Olfaction 675, 899, , Olfactory, bulb 1029, glomeruli 1029, hyperesthesia 1030, mucus membrane 1028, 1029f, organ, accessory 1028, pathway 1028, receptors 1028, sensation 1029f, sensation, abnormalities of 1030, stria 1029, tract 1029, transduction 1029, Oligodendrocytes 774, Oligomenorrhea 393, 491, Oligospermia 472, Oligozoospermia 472, 496, Oliguria 337, Olivocerebellar tract 871, 866, 873, Olivospinal tract 820, Omega-3 fats 292, Omega-6 fats 292, Oncotic pressure 30, 62, 159, One, muscle fasciculus 170f, way conduction 800, Oocyte maturation inhibiting factor 483, Open pneumothorax 734, Opioid, neuromodulators 794t, peptides 792, Opisthotonos 907, Opsin 980, Opsonization 114, Optic chiasma 990, 994, Optic chiasma, effects of lesion of 992, Optic disk 969, 970, 971, Optic nerve 970, 990, 994, connections of visual receptors to 990, effects of lesion of 992, Optic, papilla 971, pathway 989, radiation 991, 992, radiation arises 991, tract 991, 994, Optical, axis 966f, reflexes 845, righting reflexes 916, Optimum load 185, Oral, anticoagulants 134, contraceptives 514, rehydration, solution 56, therapy 56
Page 1091 :
1070 Essentials of Medical Physiology, serrata 968, stage 272f, temperature 359, Orbiculus ciliaris 968, Orbital cavity 966, Orbitofrontal cortex 891, Organ 4, of corti 1011, 1012f, system 4, transplantation 432, Organelles, in cytoplasm 6, with limiting membrane 6, 7, without limiting membrane 7, 11, Organic substances 52, Organification 390, Organs 465, Organs of pelvis 456f, Origin 104, depending upon 764, insertion and nerve supply 1009, of plasma proteins 62, Orthograde degeneration 771, Orthostatic, hypotension 616, 660, syncope 616, Oscillator 1023, Oscillatory method 613, Osmolality 54, Osmolar concentration of gastric, content 274, Osmolarity 54, Osmoreceptors 860, Osmosis 30, Osmotic, diuresis 329, 349, 423, equilibrium 244, fragility 95, pressure 30, Osseous spiral lamina 1010, Ossicular conduction 1017, Osteoblastic activity 410, 412, 431, 479, Osteoblasts 378, 400, 410, Osteocalcin 410, Osteoclastic activity 400, 411, 431, Osteoclasts 400, 411, Osteocytes 410, 411, Osteomalacia 338, 414, Osteomalacia, causes of 414, Osteones 410, Osteoporosis 412, 431, 479, 495, causes of 413, manifestations of 413, Osteoprogenitor cells 410, Other organs of pelvis 473f, Otic cochlea 1011, Otitis media 1022, , Otolith, membrane 922, organ or vestibule 920, Otoliths 920, Otosclerosis 1022, Outer, cartilaginous part 1007, cortex 303, hair cells 1012, nuclear layer 969, parietal pericardium 520, phalangeal cells 1012, pillar cells–rods of corti 1011, plexiform layer 970, pyramidal layer 885, segment 979, serous layer 230, strip 885, Outside-out patch 194, Oval window 1010, Ovarian, changes during menstrual cycle 483, changes, regulation of 488, follicle 476, 477f, 483, 485f, hormones 477, 488, Ovariectomy 494, Ovaries 476, 500, Ovary 476, Ovary, abnormalities of 496, Over ventilation 725, Overdistention of hollow organs 840, Overflow, dribbling 344, incontinence 344, Overhydration 56, Overshoot 191, Ovulation 484, 492, absence of 497, process of 484, 492, 493f, time 493, Ovulatory surge for LH or luteal surge, 489, Ovum 476, 492, changes in 483, discharge of 484, fertilized 486, Oxalate compounds 134, Oxidation of iodide 389, Oxidized cellulose 135, Oxygen 631, 727, carrying capacity of, blood 712, hemoglobin 712, consumption 578f, content in arterial blood 577, diffusing capacity for 706, diffusion of 707, , partial pressure of 737, therapy 662, therapy, treatment for 728, toxicity 729, toxicity, effects of 729, Oxygenated blood 250, 678, Oxygenation 77, of hemoglobin 711, Oxygen-binding pigment in, brain 78, muscles 78, Oxygen-hemoglobin dissociation curve, 712, 712f, Oxytocin 382, 504, on mammary glands, action of 382, , P, P cells 308, 522, 527, P wave 553, Pacemaker 527, abnormal 569, artificial 569, cells 521, 527, in amphibian heart 527, potential 528, 528f, 529, Pacinian corpuscle 912, Packaging of materials 9, Packed cell volume 67, 86, 87f, Pain 809, 810, 812, 838, acute 838, nerve endings in brain 286, pathway 841f, receptors 720, sensation 791, 839, sensation, benefits of 838, Palatal glands 224, Pale muscles 179, 180t, Paleocerebellum 865, 870, proper 865, Paleocortical structures 898, Paleospinothalamic fibers 839, Pallesthesia 829, Pallidohypothalamic fibers 856, Pallidum 884, Palpatory method 612, Palpebral fissure 967, Pancreas 241, 285, Pancreatic, amylase 287, enzymes, absence of 247, juice, collection of 247, composition of 242, 242f, digestive enzymes of 245t, digestive functions of 242, properties of 242
Page 1092 :
Index 1071, lipase 243, 293, lipolytic enzymes 293, polypeptide 285, 420, polypeptide, actions of 420, secretion, regulation of 245, somatostatin 420, Pancreatitis 247, Pancreatitis, acute 247, Paneth cells 261, Panhypopituitarism 385, Panting method 361, Papaver somniferum 792, Papez circuit 899, 900f, Papilla 303, Papillae of dermis 646, Papillary, ducts 308, muscles 522, Para-aminohippuric acid 336, Paracelluar route 320, Paracortex 156, Paracrine messengers 367, Paradoxical, sleep 932, splitting 546, Parafollicular cells 388, 404, Paralgesia 843, Parallel fibers 865, Paralysis 182, 837, causes for 837, of limbs 821, Paralytic secretion of saliva 229, Paramedian, group 901, lobe 864, Paranoid thoughts 393, Paraplegia 821, 837t, in extension 822, in flexion 822, Paraproteinemic peripheral neuropathy 65, Parasympathetic, blockers 959, division 957, fibers 227, 958, to parotid gland 227, to submandibular 227, nerve fibers 221, 589, nerve supply 341, to parotid gland 228f, to submaxillary 227f, tone 590, vasodilator fibers 606, Parasympathomimetic drugs 228, 959, Parathormone 400, 407, 408, actions of 400, on blood, calcium level, actions of 400, , phosphate level, actions of 402, receptors 402, secretion, regulation of 402, Parathyroid, function tests 404, glands 399, 502, disorders of 403, on posterior 400f, on posterior surface of thyroid, gland 400, Parathyroidectomy 403, Paraventricular nucleus 382, Paravertebral or sympathetic chain, ganglia 954, Parenchyma of testis 456, Paresthesia 93, Parietal lobe 892, Parietal lobe, areas and connections, of 894t, Parieto-occipital sulcus 886, Parkinson disease 763, 882, causes of 882, treatment for 883, Parkinsonism or paralysis, agitans 882, Parotid glands 223, Paroxysmal tachycardia 567, Pars intermedia 375, Part of, actin filament 173f, ejection period 544, Partial, heart block 566, 590, pressure 708t, pressure of oxygen 737, 738t, prothrombin time 135, Parts and functional divisions of, cerebellum 864f, Parts of, adrenal gland 425, anterior pituitary 376, bone 409, brain 757, 758f, central nervous system 757f, cerebellum 863, cerebral cortex 885, 885f, conductive system 530, dark adaptation curve 984, large intestine 266, long bone 409f, nephron 307f, pituitary gland 376f, red nucleus 845, stomach 230, 231f, superior and inferior, vermis 864t, Parturition 498, 503, , Passage of, sperms 457f, urine 308, Passive, artificial immunization 116, immunization 116, natural immunization 116, reabsorption 320, tension 185, transport 27, Patch clamp, configurations 193, 194f, technique 193, 767, Patellar clonus 799, Patent ductus arteriosus 550, 650, Pathological, hypertrophy 20, metaplasia 20, polycythemia 69, reflexes 799, splitting 545, 546, tetanus 182, variations 84, 124, in different types of WBCs 100t, of venous pressure 618, Patient with conductive deafness 1023f, Patrick wall 841, Pattern of capillary system 641, Pavlov pouch 234, 235f, Pavor nocturnus 934, PCV, increase in 86, Peak expiratory flow rate 697, Pectus carinatum 413, Peculiarities of capillary blood flow 642, Pedicles 306, Pedicles or feet 316, Pelvic, nerve or nervus erigens 341, organs 955, region 840, Pelvis 478, of ureter 308, Pendrin 390, Pendular movements 277, 799, 876, Pendulum of clock 277, Penis 466, Pepsin 232, 291, Pepsin, action of 232, Peptic ulcer 240, Peptide 284, mechanism 860, YY 238, 285, Peptone, C-type lectin 134, Percutaneous, insertion of catheter 580, transluminal coronary angioplasty, 581, 633
Page 1093 :
1072 Essentials of Medical Physiology, Perfusion pressure 600, Pericardial, cavity 520, space 520, 585, Pericardium 520, Perichoroidal space 968, Pericytes 641, Perilymph 1010, 1019, Perilymph or periotic fluid 919, Perimenopause 491, Perimysium 169, Perineural spaces 950, Periodic breathing 723, 731, 731f, Periods of simple muscle curve 178, Periosteum 409, Periotic or osseous canal 1010, Peripheral, arterial pulse 622, resistance 575, 597, 604, Peripheral, chemoreceptors 721, nervous system 758, neuroglial cells 774, proteins 6, resistance 575, 597, 618, resistance, determinants of 597, utilization 378, veins 617, venous pressure 617, Peristalsis 274, in fasting 278, Peristaltic, movements 277, rush 278, wave 342, Peritoneal dialysis 347, Peritoneum 230, Peritubular capillaries 313, Perivascular spaces 950, Periventricular fibers 856, Perivitelline space 483, Permanent anosmia 1030, Permeability of, capillary membrane 319, cell membrane 29, 372, Permissive action of glucocorticoids 431, Pernicious anemia 93, 233, Peroxidase 397, Peroxisomes 10, Persons susceptible to heatstroke or, sunstroke 747, Petit mal 936, Petit mal, causes of 936, pH 42, pH of gastric content 274, Phacoemulsification 977, Phagocytic function 152, , Phagocytosis 34, 102, 256, Phantom limb pain 779, Pharyngeal, epithelium 375, stage 271, 272f, Pharyngoesophageal sphincter 271, Phases of, action potential 525, gastric secretion 235, respiration 673, Phasic changes in, coronary blood flow 630, 631f, left ventricle 630, right ventricle 631, velocity of blood flow 599, Phasic receptors 777, Phenylalanine 439, hydroxylase 439, Phenylethanolamine-nmethyltransferase 440, Pheochrome cells 439, Pheochromocytoma 442, 443, Pheochromocytoma, cause of 442, Pheromones 358, 1028, Philipson reflex 822, 823, Phlebogram 538, 628, Phonocardiogram 541f, 548, Phosphate 408, blood level of 402, buffer system 44, buffer system, importance of 44, importance of 408, level, regulation of 408, mechanism 331, metabolism 408, Phosphatidylcholine 5, Phosphatidyletholamine 5, Phosphatidylglycerol 5, Phosphatidylinositol 5, Phosphatidylserine 5, Phospholipase A 244, Phospholipase B 244, Phospholipids 5, 122, Photopic vision 980, Photopsin 983, Photoreceptors or electromagnetic, receptors 979, Photosensitive pigments in cones 983, Phototransduction 982, Phototransduction cascade 983f, of receptor potential 982, Physiologic tremor 911, Physiological, changes during sleep 931, conditions, bradycardia occurs 588, tachycardia occurs 564, 587, , dead space 701, hyperplasia 19, 20, jaundice 68, metaplasia 20, neuronography 897, or functional divisions of, cerebellum 865, polycythemia in, emotional conditions and exercise, 69f, high altitude 69f, shunt 630, 678, vs physiological dead space 679, shunts 641, splitting 545, 546, syncytium 521, tetanus 182, variations 84, 99, 123, 148, of venous pressure 618, Physiology of, bone 399, 409, pain 838, sleep 931, Piezoelectric crystals 630, Pigeon chest 413, Pigment granules 969, Pigmentation of skin 353, Pill method 514, Pill method and pills 514, Pill-rolling movements 882, Pilocarpine 959, Pineal gland 444, Pinna 1007, Pinocytic vesicles 391, Pinocytosis 34, 643, Pitch 1020, Pithed frog 527, Pithing 527, Pitting edema 162, Pituicytes 381, Pituitary, cachexia 386, gland 375, development of 375, disorders of 384, 384t, divisions of 375, origin of Cushing syndrome 434, stalk 375, Place theory 1020, Placenta 500, 505, Placenta and embryo, development, of 499, Placental, barrier 143, detachment 143, estrogen, actions of 506, hormones 504, 511
Page 1094 :
Index 1073, progesterone, actions of 506, villi 500, Plantar reflex, abnormal 799, Planum semilunatum 921, Plasma 60, action on 392, clearance 335, composition of 59f, level 389, 405, 415, 462, 477, 480, of catecholamines 439, of mineralocorticoids 426t, membrane 4, proteins 61, edema to decreased amount, of 161, properties of 62, substitutes, administration of 662, testosterone in different ages of male, humans 462f, transfusion 662, volume 149, 931, Plasmalemma 4, Plasmapheresis 63, Plasmin, formation of 132, Plasminogen activator 132, Plateau 526f, Plateau or final depolarization 526, Platelet 72f, activating factor 102, 116, 123, 128f, derived growth factor 123, 124, disorders 125, granules 123, plug formation 127, substitute 135, Platelets 122, development of 125, grouping of 124, properties of 124, Plethysmograph 695, Plethysmography 694, 695, Pleura 674, cavity 674, in abnormal conditions 674, effusion 735, effusion, causes of 736, sac 674, Pneumocystis carinii 118, Pneumonia 734, Pneumonia, causes of 734, Pneumotachograph 695, Pneumotaxic center 718, Pneumothorax 674, 734, Pneumothorax, causes of 734, Podocytes 306, 316, Poikilocytosis 70, Poikilothermic 178, Poikilothermic animals 359, , Point of, contraction, stimulus 182f, Poisoning 729, Polar cushion 310, Poles, depending upon number of 759, Polkissen 310, Polycythemia 68, Polycythemia vera 70, Polydactylism 862, Polydipsia 423, Polygraph 541, Polymenorrhea 393, 491, Polyphagia 423, Polypnea 723, Polysaccharides 287, Polysome 16, Polysynaptic reflexes 797, 912, Polyunsaturated fats 292, Polyuria 329, 421, 423, Pons 845, Pontine centers 717, Pontocerebellar tract 872, 873, Poor localization of sound 1015, Porous bones 412, Porphyrin 78, Porphyropsin 983, Portal, system 314, triads 249, vein 251, vessels 376, Portion of parasympathetic, division 957, Portions of myosin molecule 172, Positive, after potential 191, afterimage 1001, feedback mechanism 41f, 383, feedback mechanism–parturition 41f, Positive G 740, Positive G, effects of 740, Positive sign, Babinski 799, Positive supporting reflexes 916, Positron emission tomography 635, Postcatacrotic waves 623, Posterior, end knob 472, funiculus 806, gray commissure 804, group of nuclei 848, 848f, hypothalamic nucleus 361, intermediate, septum 804, sulcus 804, limb of internal capsule 853, lobe of cerebellum 864, , median, septum 804, sulcus 804, nerve root ganglion 807, pituitary 381, semicircular canal 924, spinocerebellar tract 811, surface of liver 250f, white column 806, 813, Posterolateral sulcus 804, Posteromarginal nucleus 805, Posteroventral nucleus 1025, Posthepatic jaundice 258, Postmenopausal, symptoms 495, syndrome 494, syndrome, cause of 494, Postpartum hemorrhage 651, Postprandial 421, Postrotatory, nystagmus 926, 927, reactions 926, 927, Postsynaptic, membrane 201, 782, or direct inhibition 783, Postural reflexes 845, 915, Postural reflexes, classification of 915, Postural syncope 660, Posture 618, 662, 913, basic phenomena of 913, of body for lumbar puncture 951, Pot belly 435, Potassium, Channel, diseases 37, and efflux 526, ion concentration 570, ions 427, retaining diuretics 349, sodium-potassium pump 31, sparing diuretics 349, Potency 389, Potency and duration of action 389, Pott curvature 414, Poverty of movements 881, 882, Power, of muscle 214, plant 11, stroke 195f, PP cells 285, P-R interval 556, Practice contractions 503, Pre-Bötzinger complex 719, Precapillary sphincter 641, Precatacrotic 623, Precentral cortex 887, Precipitation method 61
Page 1095 :
1074 Essentials of Medical Physiology, Precocious pseudopuberty 466, Precursor cells 457, Pre-diabetes 422, Prednisolone 434, Pre-eclampsia 501, Pre-emulsified fats 226, Preferential channels 641, Preformed mediators 104, Prefrontal cortex 891, Prefrontal cortex, connections of 891, Pregnancy 69, 148, 498, Pregnancy tests 508, Pregnanediol 493, Pregnant uterus 383, Prehepatic jaundice 258, Prekallikrein 451, Premenstrual stress 491, syndrome 491, tension 491, Premotor area 889, Preoptic thermoreceptors 860, Preparation of, animals 906, food for swallowing 225, Preparatory stage 272f, Preproglucagon 285, 418, Prepro-PTH 400, Prepubertal boys 466, Presbyopia 973, 998, 1006, Presbyopia, causes of 1006, Presence of agglutination of latex, particles 509, Presenting cells 110, 112, Pressor area 588, 606, Pressoreceptors 591, 607, Pressure 534, arm lift method 750, bottle 582, changes during cardiac cycle 538t, determining filtration 317, diuresis 427, 609, exerted by cerebrospinal fluid 950, gradient 596, 706, gradient in different areas of vascular, bed 597t, ventilator 750, volume curve 688, 688f, Pressurized air 743, Prestin 1019, Presynaptic 783, inhibition 784f, inhibitory neuron 784, membrane 201, 782, Pretectal nucleus 991, 995, Prevent blood clotting 134, 135, Prevention of, autoimmune disorders 458, , dust particles 675, effects of g forces on body 741, Prickle cell layer 352, Primary, active transport 31, of sodium 31, addison disease, causes for 437, angle-closure glaucoma 976, auditory area 893, auditory area, connections of 894, bile acids 252, bronchi 674, colors 1000, digestive organs 219, evoked potential 897, expiratory muscles 683, follicle 483, hyperaldosteronism 404, 436, 446, hypertension 614, 615, inspiratory muscles 682, motor area 888, motor area, connections of 888, oocyte stage with diploid number, 498, open-angle glaucoma 976, peristalsis 271, peristaltic contractions 271, polycythemia 70, sensory nerve fiber 909, sex organs 455, 456, 473, 476, spermatocyte 459, taste sensations 1025, tissues 3, Primitive germ cell 458, Primordial follicle 476, 483, Principle of, blood typing 140, blood typing–agglutination 140, dialysis 347f, voltage clamping 767, Prism 999, Private pathway 990, Probing single cell 193, Procedure of, cardiac catheterization 580, heart-lung preparation 582, measure functional residual capacity, 694, measure residual volume 694, Process of, bone remodeling 411, erythropoiesis 72, exocytosis 36f, filling 342, glomerular filtration 316, hearing 1018, hemolysis 95, , lactation 512f, ovulation 484, 492, 493f, phagocytosis 35f, pinocytosis 34f, urine formation 315, Processing, of materials 9, T lymphocytes 445, Procoagulants 135, Production of, energy 11, female sex hormones in males 465, Products from, prostate gland 472, seminal vesicles 472, Proenzyme 129, Proerythroblast 73, Progesterone 433, 465, 479, 488, 506,, 510, Progesterone secretion, regulation, of 481, Proglucagon 418, Prognathism 384, Programed death 17, Progressive, hepatolenticular degeneration 883, stage of circulatory shock 657f, weakness and ataxia 93, Projected vector 560, Projection fibers 868, Prokaryotes 13, Prolactin 511, Prolactin-inhibitory hormone 377, Proliferative phase 487, 488, 490, Proliferative phase, changes in, endometrium during 487, Proline-rich proteins 226, Prolonged, hypersecretion 418, standing 660, Promotes, peripheral utilization of glucose 416, storage of glucose 416, Promoting anabolism of proteins, indirectly 378, Promotion of heat, loss 361, production 362, Pro-opiomelanocortin 860, Properties composition of, bile 251, cerebrospinal fluid 949, Properties of, action potential 190, 193t, 767, aqueous humor 971, bile 251, blood 58
Page 1096 :
Index 1075, electrotonic potential 767, endplate potential 201, EPSP 783, gastric juice 232, nerve fibers 766, normal urine 333, pancreatic juice 242, plasma proteins 62, platelets 124, prostatic fluid 468, receptor potential 778, receptors 776, red blood cells 67, reflexes 800, saliva 224, semen 470, seminal fluid 467, skeletal muscle 176, sound 1020, succus entericus 262, synapse 785, urine 333, white blood cells 101, Proprioceptors 720, 751, 776, 908,, 908t, Pro-pth 400, Propulsive movements 277, 278, Prosecretin 283, Prosencephalon 758, Prostacyclin 447, 449, Prostaglandin 311, 446, 447, 499, 504,, 611, administration of 515, G2 447, H2 447, Prostaglandins 447, action of 446, and related hormones 448f, chemistry of 447, related hormones 447, Prostate gland 466, 468, Prostate gland, products from 472, Prostatic, sinuses 340, urethra 340, Prosthetic valve 580, Protanomaly 1003, Protanopia 1003, Proteases 104, Protection from, bacteria 354, mechanical blow 354, toxic substances 354, ultraviolet rays 354, Protective, function 232, 233, 262, 354, 409, 950, reflexes 796, , Protein 285, anabolic activity of testosterone 463, androgen-binding 458, buffer system 44, in erythrocytes 44, in plasma 44, channels 27, deficiency anemia 91, hormones 372, kinase 417, layers of cell membrane 5, metabolism 378, 416, 419, 430,, 479, 501, 507, metabolism, action on 391, Proteins 8, 123, 132, 189, 285, 410, 684, absorption of 264, 290, 291, addition of 158, and amino acids 76, digestion of 242, 290, 290t, in diet 290, metabolism of 290, of tight junction 22, of muscle 172, 173, of respiratory chain 11, Protein-sparing effect 417, Proteinuria 334, 337, Proteoglycans 6, 409, 921, Proteolytic enzymes 262, 499, in pancreatic juice 291, succus entericus 291, Prothrombin, activator, formation of 130, time 135, Protodiastole 536, 539, 543, Protodiastolic period 546, Proton acceptor 42, Protonated substance 43, Protopathic sensations 829, Protoplasmic astrocytes 773, Proximal, centriole 472, convoluted tubule 306, 328, muscles 834, part of distal convoluted tubule 349, Pseudoglobulin 61, Pseudohermaphroditism 438, Pseudohypertrophy 211, Pseudohypoparathyroidism 403, Pseudopods 391, Psychic phenomenon 751, Psychogenic dwarfism 386, Psychomotor epilepsy 936, psychomotor epilepsy, causes of 936, Psychosocial dwarfism 386, PTH-related protein 402, Ptosis 998, Pudendal nerve 279, 341, , Pulmonary, area 548, arterial pressure 679, artery 678, blood flow 679, chemical factors of 680, regulation of 679, blood, pressure 679, vessels 678, 679, capillary, pressure 679, to alveolus, diffusion of carbon, dioxide from 707f, wedge pressure 537, circulation 524, 524f, 678, edema 161, 735, edema, causes of 735, function tests 690, hypertension 740, surfactant 684, tuberculosis 736, valve 522, vascular resistance 648, veins 678, ventilation 700, 740, ventilation, definition of 700, Pulsatile, flow 598, secretion of GNRH 488, Pulse, abnormal 625, delay in transmission of 623, delayed 625, generator 569, in aortic regurgitation, abnormal 626, in patent ductus arteriosus,, abnormal 626, points 623, 624t, pressure 603, rate 624, decreases 624, different age 624, increases 624, Pulsus, alternans 625, deficit 625, paradoxus 625, Pump handle movement 683, Punctate basophilism 70, Punctum, proximum 998, remotum 998, Punishment centers 861, Pupil 797, 968, constriction of 985, dilatation of 799, 983
Page 1097 :
1076 Essentials of Medical Physiology, Pupillary, dilator muscle 968, light reflex 994, light reflex, direct 994, reflexes 798, 994, Pure oxygen 694, Purkinje, cells 784, 865, fibers 529, layer 865, phenomenon 1000, sanson images 996, 996f, shift 1000, Purple striae 435, Purpura 136, Purpuric spots 136, Pursuit movement 975, Pus 102, Pus cells 102, Pyknosis 74, Pyloric, glands 231, region 230, sphincter 261, 274, Pyothorax 674, Pyramidal 835, cells 885, lobules 456, tract lesion 799, tracts 814, 835, Pyrexia 362, Pyridostigmine 212, Pyrrole rings 78, , Q, QRS complex 554, Q-T interval 557, Quadriplegia 818, 821, 837t, Quadruple, heart sound 547, rhythm 547, Qualities of, semen required for fertility 472, stimulus 176, Quantity of, flatus 280, solids excreted in urine 333f, Quick component 926, Quiescent heart 530, of frog 532f, Quiet heart 530, , R, Rabbit antiserum 509, Radial, artery 623, , femoral delay 625, pulse tracing 623f, in patent ductus arteriosus 626f, radial delay 625, Radiation, method 361, of heat from environment 360, Radioactive substances 635, Radiofemoral delay 625, Radiographic study 542, Radionuclide angiocardiography 535, Radiopaque contrast 581, medium 542, Rage 861, Range of accommodation 998, Raphe group 901, Rapid, and slow filling periods 628, blood flow 600, eye movement sleep 932, 932t, filling phase 536, 543, influx of sodium ions 526, jerky movements 883, phase 400, Ratchet theory 195, Rathke pouch 375, Rattle snakes 135, RBC count 85, RBCs See also red blood cells 97, Reabsorption 160, of amino acids 323, of bicarbonate 323, of bicarbonate ions 330, of electrolytes 349, of glucose 323, of important substances 322, of sodium 322, 326, of water 322, Reaction and pH 58, of neighboring tissues after necrosis, 19, rotation with opened eyes 927, Reactive hyperemia 631, Rebound phenomenon 801, 877, Recanalization 515, Receiving area 872, Receptive relaxation 274, Receptor 313f, 775, 795, 839, 1013,, 1025, classification of 775, coated pit 35, mediated endocytosis 35, of neurotransmitter 958, organ 1011, in otolith organ 922, in semicircular canal 921, in vestibular apparatus 920, , potential 777, 778, 982, 983, 1019, potential, properties of 778, properties of 776, β estrogen 479, Reciprocal, inhibition 784, 801, 801f, 802, innervation 801, Recirculation of urea 326, Recovery, heat 199, of muscle after fatigue 181, Recruitment of motor units 203, Rectal temperature 359, Red, blood cells 66, 83, 72f, 77, 334, blood cells, properties of 67, muscles 179, 180t, nucleus 845, connections of 846, in midbrain 820, pulp 153, reaction 647, Redistribution of tone 913, Redout 741, Re-entered nodal impulse 568, Re-esterification of fatty acids 293, Re-excitation of heart 568, Referred pain 840, Referred pain, definition of 840, Reflected waves 576, Reflex 799, 932, activity 795, arc 795, hyperventilation 720, in motor neuron lesion 802, muscular activity, control of 881, ocular movements 818, regulation of salivary secretion 228, Reflexes 906, classification of 796, definition and significance of 795, properties of 800, Refractive power 998, Refractory period 186, 531, 769, in beating heart 531, of frog 531f, in cardiac muscle 187, 531, in quiescent heart 532, in skeletal muscle 187, 531, Refractory, power 978, stage 655, Regeneration of nerve fibers 770, 772, Regional variation in capillary pressure, 620, Regnier de graaf 484, Regular astigmatism 1005
Page 1098 :
Index 1077, Regulation of, acid-base balance 43, 45f, 60, 676, by acid-base buffer system 43, by renal mechanism 45, by respiratory mechanism 45, actions of heart 523, activity of gland 370, anterior pituitary secretion 376, arterial blood pressure 605, autonomic, functions 899, nervous system 857, bile secretion 257, blood, calcium level 302, 407, 407f, flow to liver 639, flow to spleen 639, glucose level 421, pressure 302, 858, 606f, 607,, 608f, pressure by renin-angiotensin, mechanism 609f, volume 150, body temperature 60, 226,355, 361,, 362f, 676, 858, bone remodeling 412, calcitonin secretion 405, capillary pressure 620, 621f, cerebral blood flow 635, channels 28, conscious movements 881, cortisol secretion 433f, cranial content volume 950, cutaneous blood flow 646, endocrine glands 899, estrogen secretion 479, estrogen secretion 479f, extracellular fluid volume 609, food intake 900, gastric emptying 274, gastric secretion 234, 236f, Gh secretion 379, 380f, glomerular blood flow 311, glucagon secretion 419, heart rate 588, 858, hormone receptors 372, hunger and food intake 858, insulin secretion 417, menstrual cycle 488, mesenteric blood flow 638, muscle tone 914, ovarian changes 488, pancreatic secretion 245, parathormone secretion 402, phosphate level 408, progesterone secretion 481, pulmonary blood flow 679, , renal blood flow 313, respiration 716, salivary secretion 227, secretion 376, 382, of adrenaline 442, of somatostatin 420, of succus entericus 264, of thyroid hormones 394, 395f, sexual functions 861, 900, sleep 860, spermatogenesis 460, subconscious movements 881, testosterone secretion 464, testosterone secretion 465f, total iron in body 82, tubular reabsorption 320, uterine changes 490, vagal tone 591, voluntary movements 880, water 355, balance 60, 226, 860, Regurgitation 550, Reissner membrane 1010, Rejection of transplanted tissues 432, Relative refractory period 187, 531, 769, Relaxation of, biceps muscle 210f, muscle 196, 575f, Relaxation period 178, 179, Relaxin 504, 507, Relay center 851, Release of, acetylcholine 201, neurotransmitter 789, thyroid hormones from thyroid, gland 391, REM sleep 932, Removal of, carbon particles 152, catecholamines 440, excess secretory products in cells, 10, hydrogen ions 331, Renal, artery 312, autoregulation 314, blood flow 313f, 317, blood flow, regulation of 313, blood vessels 312, 312f, capillaries 313f, circulation 312, corpuscle 305, 305f, failure 337, 659, failure, acute 334, 337, function tests 333, hypertension 614, ischemia 337, , mechanism 655, mechanism for regulation of blood, pressure 608, pelvis 303, shutdown 142, sinus 303, stones 404, system 204, threshold for glucose 323, tubule 304, Renin 291, 310, 445, actions of 445, angiotensin mechanism 609, angiotensin system 310, 311f, secretion 652, Renshaw, cell inhibition 784, 784f, cells 806, Repair of bone after fracture 412, Reperfusion, injury 659, therapy 581, Replacement, therapy 495, transfusion 147, Repolarization 190, 191, of membrane under first electrode, followed 192, of ventricular musculature 556, Representation of visual pathway 991f, Representational hemisphere 887, Reproductive, cell 470, system 94, 205, 455, Requisites for blood typing 140, Residual volume 691, 691f, 693f, Resistance 523, artificial 582, or vis a latre 618, to blood flow 597, tube 582, Resistant vessels 523, 576, 597, Resolution of rigor 184, Resonance, point 1018, theory of helmholtz 1020, Respiration 93, 442, 653, 723, 728-730, action on 393, artificial 749, on venous pressure, effect of 619, regulation of 716, Respiratory, acid 46, acidosis 45, alkalosis 46, bronchioles 674, burst 102
Page 1099 :
1078 Essentials of Medical Physiology, centers 591, 608, 716, 718, 844, centers, connections of 718, disorders 726, 731, exchange ratio 710, function 60, 505, gases at tissue level 708, gases between fetal blood and, maternal blood 505, membrane 675, 705, minute volume 697, 700, movements 682, muscles 688, pressures 685, protective reflexes 677, pump 574, pump on venous return, effect of 574f, quotient 710, sinus arrhythmia 557, 562, 591, system 204, 502, 739, 931, system, changes in 740, tract 673, 674f, unit 674, 675f, Respirometer 693, Resting, condition 199, heat 199, length 186, membrane potential 188, 206, 525,, 528, tremor 882, Restoration of, Plasma, proteins 653, volume 653, red blood cell count 653, resting membrane potential 526, Restrictive, and obstructive respiratory diseases, 697, 699t, respiratory disease 699, Resuscitator 749, Resynthesis of, ATP 197, ATP by carbohydrate metabolism, 197, 199, ATP from creatine phosphate 197, rhodopsin 981f, 982, Retching 276, Rete, ridges 352, testis 457, Retention of water 382, 860, Reticular, activating system 653, formation 588, 653, 819, 901, connections of 902, definition of 901, , divisions of 902, in upper pons 718, organization of 901, layer 353, system, descending 904, Reticulocyte 74, Reticuloendothelial, cells 152, 639, cells, classification of 151, system 151, Reticulohypothalamic fibers 856, Reticulospinal tract 819, Reticulum 151, Retina 969, 979, 988, Retinal isomerase 982, Retinohypothalamic fibers 856, Retinoid X receptor 394, Retrograde, degeneration 771, ejaculation 472, Retrolenticular portion 853, Reuptake, of neurotransmitter 789, process 202, Reversal of blood flow in ductus, arteriosus 650, Reverse, chloride shift 714, osmotic pressure 30, peristaltic movement 448, 467, splitting 546, transcriptase 118, Reversed heart block 566, Reward center 861, Rexed laminae 806, Reynolds number 596, Rh, antigen 142, 143f, factor 142, incompatibility 144f, Rheobase 177, 177f, Rhesus monkey 142, Rheumatoid arthritis 93, 120, Rhinencephalon 898, Rhodopsin 979, 980, 982, Rhodopsin, chemistry of 980, Rhombencephalon 758, Rhythm method 493, 513, Rhythmic discharge of inspiratory, impulses 718, Rhythmicity 526, definition of 526, of different parts of, amphibian heart 528, human heart 527, Ribonucleic acid 16, Ribosomal RNA 16, , Ribosomes 11, Rickets 413, Rickets, causes of 413, Right and left, branches 674, 678, coronary arteries 629, Right, arm 559, atrial, hypertrophy 554, pressure or vis a fronte 618, reflex 593, atrium 519, 650f, bainbridge reflex 593, axis deviation 561, heart catheterization 580, lymphatic duct 155, side of heart 519, sided heart failure 663, vagus nerve, effect of 590, ventricle 519, 650f, Righting reflexes 916, Righting reflexes, control of 846, Rigid like pillars 882, Rigidity 882, Rigor mortis 183, Rigor mortis, cause of 183, Ring, atrioventricular 521, finger 624, in red blood cells 70, Rinne test 1023, Risk, factors for osteoporosis 413, of heart disease 295, Rod, adaptation 984, cone break 984, monochromatism 1002, Rods versus cones 981t, Rolandic fissure 886, Role as reserve proteins 63, Role in, arousal 851, mechanism 881, behavior 860, blood clotting 124, calcification 410, cellular metabolism 8, circadian rhythm 862, clot retraction 124, coagulation of blood 62, defense mechanism 125, of body 62, emotional state 900, erythrocyte sedimentation rate 63, formation of bone matrix 410
Page 1100 :
Index 1079, homeostasis 301, maintenance of osmotic pressure in, blood 62, memory 900, motivation 900, prevention of blood loss 124, production of trephone substances 63, regulation of acid-base balance 63, repair of ruptured blood vessel 124, response to smell 862, speech 226, suspension stability of red blood, cells 63, transport mechanism 62, viscosity of blood 63, Role of, ADH 328, ADH in formation of concentrated, urine 328f, amino acid level in blood 419, analgesic pathway in inhibiting pain, transmission 841, anterior pituitary 432, antigen 110, 112, auditory ossicles 1017, autonomic nerves 418, baroreceptors 607, bile salts 293, blood glucose level 417, 419, brain in gate control mechanism 842, brainstem centers 915, calcium, in exocytosis 36, ion in regulating 401, cerebellum and basal ganglia 915, cervix 503, cytotoxic T cells 111, efferent nerve fibers of hair cells, 1019, endocrine hormones 418, eustachian tube 1017, external ear 1016, factors in spermatogenesis 461, FSH 490, G proteins 373, gastrointestinal hormones 418, ghrelin in secretion 380, Golgi tendon organ in, forceful contraction 911, inverse stretch reflex 911, lengthening reaction 912, hair cells 1019, helper T cells 111, 113, hormones 360, 503, 512f, in growth of mammary glands 510, in lactogenesis 511, in spermatogenesis 460, , in spermatogenesis 461f, in the maintenance of blood, glucose level 421, hypothalamus 394, 433, in galactopoiesis 511, in secretion 379, inner, ear 1018, hair cells 1019, insulin in maintenance of blood, glucose level 421, iodide 394, kidney in, acid-base balance 330, preventing metabolic acidosis, 331, LH 489, lipid derivatives 418, liver 421, locus ceruleus of pons 933, loop of Henle in development of, medullary gradient 326, lower esophageal sphincter 272, medullary centers 718, memory B cells 113, memory T cells 112, middle ear 1017, mitochondria in apoptosis 18, motor area of cerebral cortex 914, muscle spindle in stretch reflex 910, osmoreceptors 382, other factors 394, otolith organ in resting position 926, outer hair cells 1019, pituitary gland 394, plasma cells 112, pontine centers 718, pressures in autoregulation 600, proteins 418, PTH in activation of vitamin D 401, raphe nucleus 933, reward 861, sertoli cell in spermatogenesis 460, suppressor T cells 112, Th1 cells 111, Th2 cells 111, troponin and tropomyosin 195, tympanic membrane 1017, uterus 503, various systems of body in, homeostasis 38, vasa recta in maintenance of, medullary gradient 327, Rotational movement 927, Rotatory 918, Roughened endothelial lining 137, Rouleaux formation 63, 67, 67f, 85, , Round window 1011, Routes of reabsorption 320, 320f, R-R interval 557, Rubber tube 693, Rubroreticular tract 874, Rubrospinal tract 820, 874, Rubrothalamic tract 874, Rudimentary 510, Rugae 339, , S, S cells of duodenum 283, Saccadic movement 975, Saccules 979, Sacral, ganglia 955, nerves 221, outflow 958, portion of parasympathetic division, 958, Saddle back 414, Safe period 513, Saliva, composition of 225, 225f, digestive enzymes of 226t, properties of 224, Salivary, amylase 226, glands 223, 428, glands, classification of 224, secretion, regulation of 227, Salmonella 268, Salt receptor 1027, Salt taste 1026, Saltatory conduction 768, 768f, Salting-out method 61, Salt-retaining effects 427, Sandwich of lipids 4, Santorini, duct of 241, Sarcolemma 169, 521, Sarcomere 171, 171f, 205, 521, definition 171, in resting muscle 172f, Sarcoplasm 169, Sarcoplasmic reticulum 174, Sarcotubular system 174, 205, 521, Satellite cells 774, Saturated fats 292, Saturation of hemoglobin with oxygen, 712, Scaffold 23, Scaffolding 173, Scala, media 1011, tympani 1011, vestibuli 1010
Page 1101 :
1080 Essentials of Medical Physiology, Scavengers 676, Schlemm, canal of 972, Schwann cells 762, 774, Sclera 967, Scotopic vision 980, 985, Scrotum 456, Scuba 745, Seat of fatigue 181, Sebaceous glands 356, 966, 1007, Sebum 356, composition of 356, sebaceous glands 355, Second, degree of injury 770, heart sound 536, 546, 548, and ECG 546, cause of 546, order neurons 807, 839, 922, 989,, 1013, 1014f, 1025, period of sexual life in females 475, polar body 499, stage or, progressive stage 655, slow ejection period 535, Secondary, active transport 32, auditory area 894, bile acids 252, bronchi 674, diabetes mellitus 423, diabetes mellitus, causes of 423, hyperparathyroidism 404, 436, hypertension 614, 615, liquefaction 470, oocyte 498, first polar body 498, peristaltic contractions 272, polycythemia 70, sensory nerve fiber 910, sexual characters in female 478, spermatocytes 459, tympanic membrane 1011, Secretin 238, 246, 289, 949, Secretin, action of 246, Secretion 75, 377, 382, 400, 404, 415,, 420, 426, 477, 479, 762, Secretion of, adrenaline, regulation of 442, androgens 461, angiotensin-converting enzyme 676, antidiuretic hormone 350, 653, bactericidal agents 152, bicarbonate ions 244, bile 251, 255, catecholamines 653, colony-stimulation factor 152, gastric juice 234, , hormones 310, 485, hydrochloric acid 234, in parietal cell of gastric gland, 234f, hydrogen ions 330, in renal tubule 331t, interleukins 152, large intestine 267, mucin 256, neurotransmitter 765, pancreatic, enzymes 244, polypeptide 420, pepsinogen 234, platelet-derived growth factor 152, posterior pituitary hormones 381,, 857, pulmonary surfactant 684, regulation of 376, 382, sebaceous gland 456, somatostatin, regulation of 420, substances 311, succus entericus, regulation of 264, testosterone from leydig cells 460, thyroxine 40, transforming growth factor 152, tumor necrosis factors 152, Secretory, activity of, apocrine glands 357, eccrine glands 357, function 10, 263, 267, 355, of cells in gastric glands 232t, lysosomes 10, phase 487, 488, 490, phase, changes in endometrium, during 487, vesicles 10, Section of, heart 520f, spinal cord 804f, uterus 474f, Sed rate 83, Seddon neuropraxia 770, Segment III 343, Segmental, artery 312, static reflexes 917, Segmentation contractions 277, 278, Segments of spinal cord 803, Seizures 502, Selective, permeability 6, 23, of cell membrane 189, reabsorption 320, Self blood donation 147, Self-excitation 526, , Self-regenerative 343, Semen 470, analysis 472, clotting of 467, 468, composition of 470, 471f, properties of 470, Semicircular canals 920, by rotation, effects of 927, effects of 926, Semilunar valves 522, 546, Semilunar valves, closure of 539, Seminal vesicles 466, 467, Seminal vesicles, products from 472, Seminiferous tubules 456, 457, Senile decay 386, Sensation of, classification of 829f, definition and types of 828, smell 1028, taste 1024, vibration 829, Sensitivity of cone pigments 984t, Sensory 830f, and motor nerve supply 909, area 589, cerebral cortex 813, changes 823, fibers of trigeminal nerve 830, function 354, motor area 893, nerve 591, 795, fibers 765, fibers from heart 591, fibers, destruction of 344, supply 909, or afferent neurons 760, pathways 633, 829, 831t, transduction 777, Separation of plasma proteins 61, Sepsis 661, Septa of heart 520, Septal defect 550, Septic shock 661, occurs 661, Sequence of, clotting mechanism 129, events, activation of B cells 112, activation of helper T cells 111, in intrinsic pathway 130, in stage 2 130, involved in activation of, plasminogen 132, muscular relaxation 197f, oral stage 271, postsynaptic 783f, Sequential pills 514
Page 1102 :
Index 1081, Serine and cysteine proteases 418, Serotonin 104, 449, 610, 790, Serotonin, actions of 450, Serous, fluid 487, glands 224, layer 266, 521, membrane 221, or fibrous layer 221, or outer layer 474, Sertoli cells 458, Serum 60, globulin 61, spreading factor 123, Servomechanism 875, Severe, anemia 144, dehydration 55, 56, exercise 666, hemorrhage 652, hypothermia 363, Severity of, exercise 665, transfusion reactions 142, Sex, chromosomes 459, 499, differentiation 499, differentiation in fetus 462, hormones 426, hormones, adrenal 433, organs, accessory 455, 473, steroid-binding globulin 462, Sexual, function, action on 393, functions, regulation of 861, 900, life in females 475, Sham, feeding 235, rage 861, Shape of, platelets 122, spinal cord 803, Sheath of Schwann 762, Sheep’s red blood cells 509, Sherrington, law 801, reciprocal innervation 917, Shigella 268, Shivering 360, 362, 746, Shock 654, anaphylactic 661, cardiac diseases 661, obstruction of blood flow –, obstructive shock 661, to decreased blood volume 659, to increased vascular, capacity 660, , Short, axons 760, loop feedback control 379, process 1008, term, memories 891, regulation 605, tracts 807, Shunt in capillaries vs shunt in heart 642, Sick sinus syndrome 564, Sickle cell 70, anemia 91, 92f, disease 91, Sign, Babinski 799, 817, Babinski negative 799, Babinski positive 799, Chvostek 404, Signal generator 767, Signaling cells 367, Silent, area or association area 891, flow 596, Silicon 152, Simmond disease 386, Simple, diffusion lipid layer 27, diffusion protein layer 27, muscle, contraction 178, curve 178, reflex arc 795f, Simultaneous, contrast 1001, movements of both eyeballs 975, Single, gene disorders 14, unit or visceral smooth muscle, fibers 205, unit smooth muscle fibers 205, Sinoaortic mechanism 593, 608, Sinoatrial, block 554, 565, node 527, 529, Sinus, arrhythmia 562, 563f, bradycardia 564, occurs 564, tachycardia 563, 564, occurs 564, venosus 528, Site of, erythropoiesis 71, fatigue 181, formation 949, reabsorption 320, referred pain 840f, , Situation of, depending upon situation 167, pineal gland 444, spinal cord 803, Size, and cells of different parts of, nephron 308t, of ions 29, of molecules 29, of platelets 122, Sjögren syndrome 229, Skeletal, growth factors 410, muscle 167, 168t, 170f, 187, 442,, action on 393, action potential in 191f, circulation 644, composition of 174f, mass 170t, properties of 176, muscles 764, muscles–myopathy, disorders, of 211, Skilled movements, control of 846, Skin 93, 301, 351, 442, 478, 652, 839, Skin, color of 353, Sleep, action on 393, apnea 724, syndrome 934, centers 933, disordered breathing 724, disorders 934, inducing centers 933, requirement 931, start 934, terror 934, Sleeping sickness 904, Sliding, mechanism 196f, theory 195, Slow, component 926, filling phase 536, 540, 543, influx 526, pain fibers 839, phase 401, synaptic transmission 788, Slowness of movements 882, Slow-reacting substances of, anaphylaxis 104, Slow-wave potential 206, Slow-wave rhythm of resting membrane, potential, Slow-wave sleep 932, Sluggish blood flow 600, Sluggishness of blood flow 137, 733
Page 1103 :
1082 Essentials of Medical Physiology, Small, intestine 261, 284, 285, 291, lymphocytes 98, Smaller action potential 784, Smallest skeletal muscle 1009, Smallpox 118, Smoke from 79, Smooth, endoplasmic reticulum 8, muscle 168, 187, 204, 442, control of 209, distribution of 204, fibers 168t, 205f, Snake venom 135, Snakes, cobras 135, rattle 135, vipers 135, Sneezing 675, reflex 677, reflex, causes of 677, Sodium 135, channel 526, diseases 37, chloride 318f, cotransport 33, 33f, 34f, 291, cotransport of, amino acids 33, glucose 33, counter transport 33, 34f, dependant glucose cotransporter 2, 323, glucose symport pump 416, hydrogen antiport pump 330, 331f, influx 982, ion concentration 570, ions 427, 526, 529, potassium pump 189, 526, potassium pump, abnormalities of, 37, space 53, Soft, first heart sound 545, second heart sound 546, Solubility of, gas in fluid medium 706, of substance 29, Somatic, chromosomes or autosomes 499, functions 758, motor nerve fibers 973, nerve, fibers 764, 797, supply 341, nervous system 758, reflexes 797, sensations 828, , Somatomedin 379, Somatomotor, activities, control of 905, system 832, Somatosensory, area 892, evoked potential 897, pathways 830, system 828, Somatostatin 238, 285, 420, 425, Somatostatin, actions of 420, Somatotropes 376, Somesthetic area, areas of 892, I 892, I, connections of 892, II 893, Somesthetic association area 893, Somnambulism 934, Somnolence 393, Sotonic muscular contraction 664, Sound, properties of 1020, transducer 548, transduction 1016, 1018, Sour, receptor 1027, taste 1026, Space, motion sickness 742, of nuel 1012, physiology 741, Spasm 840, 935, of sigmoid colon 269, Spastic, neurogenic bladder 344, paralysis 837, 889, 890, Spasticity 211, Spatial summation 785, 800, Special, features of renal circulation 314, sensations 828, senses 966, Specific, compliance 687, functions of lysosomes 9, gravity 62, 67, of RBC 85, receptors 828, sensory pathways 903, Specificity of, B lymphocytes 114, response 776, T cells 112, Spectral colors 999, Speech, apparatus 675, problems 882, , Speed of paper 552, Sperm 470, count 470, duct 456, Spermatic deferens 456, Spermatids 459, Spermatogenesis 458, 459f, 460, Spermatogenesis, regulation of 460, Spermatogenic cells 457, 458, Spermatogonia 457, Spermatogonium 459, Spermatozoa 458, 459, Spermatozoon 470, Spermeogenesis 380, 459, 460, Spermicidal action 514, 515, Spermination 459, 460, Sperms, abnormal 496, Spherocytosis 70, Sphincter 341, of oddi 250, pupillae 998, Sphingomyelins 5, Spike potential 191, 206, initiated by slow-wave rhythm 206, Spinal, animal 917, canal 804, cord 757, 784, 803, 817, 821, 818, 833, and pathway 813f, conus medullaris of 803, coverings of 803, descending tracts of 814, 816t, diseases of 825, filum terminale of 803, disk 826, injury 344, lemniscus 830, nerve fibers 764, nerves 803, of spinal cord 803, preparation 907, reflexes 796, segmental reflex 913, veins 950, Spindle, bursts 932, cells 484, Spinocerebellum 865, Spinocerebellum, connections of 871f, Spino-olivary tract 812, Spinoreticular tract 812, Spinotectal tract 811, Spinovestibular tract 812, Spinovisual reflex 812, Spiral, canal of cochlea 1010f, ganglion, bipolar cells of 1013, ligament 1010
Page 1104 :
Index 1083, Spirogram 693, 693f, Spirometer 692, 692f, Spirometry, disadvantages of 693, Splanchnic, circulation 638, region 576, Splay 323, in renal threshold curve for glucose, 323f, Spleen 71, 153, Splenic, circulation 639, circulation, importance of 639, contraction 639, pulp 639, venous sinuses 639, Splenomegaly 154, Splenomegaly, effects of 154, Spongy bone 410, Spongy urethra 340, Spontaneous pain 852, Spread of, action potential cardiac muscle 526, impulses from, SA node 527, sinus venosus 528, Spreading flush 647, S-T segment 557, Stable clot 131, Stage of, Blood, clotting 130, coagulation 131f, bone repair after fracture 412, circulatory shock 655, collapse 730, convulsions 730, deep sleep 933, deglutition 270, 272f, drowsiness 932, erythropoiesis 73, 73f, excitation-contraction coupling 194, flaccidity 821, growth 459, hemostasis 127, hyperpnea 730, maturation 459, medium sleep 933, metabolism of catecholamines 440, ovulation 492, pancreatic secretion 245, parturition 503, proliferation 459, recovery 822, reflex, action 236, 237, 245, 273, activity 822, failure 822, 823, , regeneration 772, sleep and eeg pattern 932, spermatogenesis 458, spermatogenic cells 457, spinal shock 821, 822, synthesis of thyroid hormones 389, transformation 459, Stagnant hypoxia 727, Stagnant hypoxia, causes for 727, Staircase phenomenon 183, 530, Staircase phenomenon, cause for 530, Stamping gait 826, Standard limb lead I 559, Stannius 527, ligature experiment 527, ligatures on Frog’s heart, effect of, 528f, Stapedius 1009, Stapes 1009, Staphylococcus 226, Starling, forces 160, 317, hypothesis 63, 159, 317, law 184, of intestine 277, State of rest for mind and body 931, States of hemostasis 128, Static, compliance 687, compliance vs dynamic compliance, 687, conditions 687, exercise 665, gamma efferent 910, lung function tests 690, postural reflexes 917t, reflexes 915, response 911, tremor 882, Statokinetic reflexes 918, Statotonic or attitudinal reflexes 917, Statue-like body 881, Steatorrhea 248, 265, Steatorrhea, causes of 248, Stellate cells 865, Stem cells 21, 72, 72f, 106, advantages of 21, from umbilical cord blood 21, Stenosis 549, of atrioventricular valves 550, of semilunar valves 550, 660, Stensen duct 223, Steps for calculation of mean qrs, vector 559, Stereocilia 922, 924, Stereognosis 813f, Sterilization permanent method 515, , Steroid hormones 371, Stethoscope 547, Stigma 492, Stimulant, for renin secretion 310, for secretion 75, 282, 283, 284, 285, Stimulation of, area 4, effect of 888, area 6, effect of 890, effect of 590, hair cells 924, left vagus nerve, effect of 590, receptor cells in semicircular canal, 924, sympathetic nerves, effect of 591, vagus nerve, effect of 590, Stimulus 272, artifact 190, definitions 176, Stirrup 1009, Stoke-Adams syndrome 370, 567, Stomach 32, 230, 284, 286, 287, 291,, 293, accommodation of 274, filling and emptying of 274, filling of 274, Stop-flow method 319, Storage function 60, 232, 255, 355, Storage of, B lymphocytes 108, bile 251, 256, blood 639, fat 416, iron 82, lipids 294, T lymphocytes 108, thyroid hormones 390, Stratum, corneum 351, germinativum 352, granulosum 352, lucidum 352, spinosum 352, Streamline 549, flow 596 596f, Strength, and stability 23, duration curve 177, 177f, of muscle 214, of stimulus, effect of 179, Streptococcus 226, Stress dwarfism 386, Stretch, receptors of lungs 719, reflex 910, 910f, 912, 915, Stretching of muscle spindle 910, Stria terminalis 856
Page 1105 :
1084 Essentials of Medical Physiology, Striated muscle 167, Striatum 879, Stridor 403, Stringomyelia, cause of 825, Stroke 297, 637, causes of 637, definition of 637, volume 572, Structural model of cell membrane 4, Structure of, axon terminals 782, bone 409, capillaries 641, cell 4, membrane 4, cerebellar cortex 866f, chemical synapse 781f, compact bone 410f, cone cell 979, corpus luteum 485, DNA 14, 15f, ear 1007, 1008f, eye 965, eyeball 967f, gap junction 23, gastric glands 231, Golgi tendon organ 911, hemoglobin 78, intestinal wall with intrinsic nerve, plexus 221f, juxtaglomerular apparatus 309, lens 972, lymph nodes 156, mitochondrion 11f, muscle spindle 908, nephron 304f, neuromuscular junction 201f, neuron 760, nucleus 13, pineal gland 444, premotor area 889, primary motor area 888, prostate gland 468, renal corpuscle 305, respiratory, membrane 706f, unit 674, RNA 16, rod cell 979, seminal vesicles 467, skeletal muscle 169, skin 351, 352f, smooth muscle 205, sperm 471, spleen 153, stomach wall 230, taste bud 1024, , testis 457f, tight junction 22, tympanic membrane 1008, uterus 474, visual receptors 979f, wall of large intestine 266, Subarachnoid space 757, 950, Subclinical tetany 403, Subconscious, kinesthetic sensation 810, 811, 829, movements, regulation of 881, Subcortical, auditory center 1014, center 991, structures 899, Subcutaneous, fat 295, tissue 151, Subdural hematoma 929, Subliminal fringe 800, 800f, Sublingual glands 224, 227, 227f, Submaxillary glands 223, Submucus layer 220, 231, 267, Subneural clefts 201, Subpapillary venous plexus 646, Substances, affecting formation of CSF 950, for measuring circulation time 599, found in body 96, necessary for hemoglobin synthesis 81, of bacterial origin 96, present in, granules 102, platelet granules 123t, reabsorbed from, distal convoluted tubule 320, loop of henle 320, proximal convoluted tubule 320, secreted, by WBCs 103t, in different segments of renal, tubules 324, to measure body fluid compartments, 54t, transported by active transport 31, Substantia, gelatinosa 839, of rolando 805, 809, nigra 845, 879, 882, Subthalamic nucleus of luys 879, Subtypes of ectopic arrhythmia 565, Subunits of insulin receptor 417, Successive contrast 1001, Succinylcholine 203, Succus, Entericus, composition of 262, 263f, , digestive enzymes of 263t, entericus, properties of 262, Sucrase 287, Sucrose space 53, Sudden withdrawal 490, Sulci 804, Sulfhemoglobin 80, Sulfhemoglobin, blood level of 80, Summation 180, 769, 785, gallop 547, of subliminal stimuli 530, Sunstroke 747, Superficial, cutaneous reflexes 798t, marginal plexus 968, mucous membrane reflexes 797t, papillary layer 353, reflexes 797, Superior, cerebellar peduncle 845, cervical, ganglion 955, sympathetic ganglion 973, colliculus 812, 820, 845, 991, hemiazygos 678, oblique 974, 975f, olivary nuclei 1013, 1014, peduncles 869, rectus 974, 975f, muscles 974, salivatory nuclei 844, semicircular canal 924, thalamic peduncle or radiation 850, vena cava 519, 583f, 650f, vermis 863, Superposition 180, Supplementary motor area 890, Supporting, cells 458, place theory 1021, reflexes 916, Supraoptic, nucleus 382, nucleus of hypothalamus 991, Suprarenal glands 425, Supraspinal, facilitatory centers 914, inhibitory centers 914, Supraventricular tachycardia 567, Surface, acting material 684, activator 135, area of, body 148, capillary membrane 319, tension 684, Surfactant 684
Page 1106 :
Index 1085, Surgical, method permanent method 515, shock 660, Suspension stability 67, Suspensory ligaments 968, Sustentacular cells 458, 593, Swallowing, apnea 677, 724, preparation of food for 225, reflex 677, Swan-Ganz catheter 538, Sweat, glands 355, 357, 428, 995, receptor 1027, secretion 932, taste 1026, Swelling of lymph nodes 157, Sylvian fissure 886, Sympathetic, and parasympathetic divisions of, autonomic nervous system 957t, blockers 958, blocking agents 633, blocking agents, actions of 959t, chain 973, cholinergic fibers 607, 644, 666, division of ANS 954, fibers 227, ganglia 954, nerve, fibers 221, 590, 973, supply 341, nerves 588, NGF 763, stimulation 319, tone 575, 591, 598, 606, vasoconstrictor tone 606, vasodilator 607, fibers 607, 644, Sympathoadrenal discharge 442, Sympathoadrenergic system 957, Sympathomimetic drugs 228, 958, Sympathomimetic drugs, administration, of 662, Symport 31, 322, Symptoms of, adrenogenital syndrome 436, carbon monoxide poisoning 733, cataract 976, decompression sickness 745, early dumping 275, glaucoma 976, hemisection of spinal cord 823, hemophilia 136, incomplete transection 822, late dumping 275, motion sickness 928, , mountain sickness 739, myocardial infarction 633, postmenopausal syndrome 494, 495, stroke 637, Synapse 780, classification of 780, properties of 785, Synaptic, cleft 201, 449, 782, delay 785, inhibition 784, terminal 979, 980, trough 201, vesicles 200, Synchronized waves 929, Syncope fainting 660, Syncytial 530, Syncytium 521, Syndrome, adrenogenital 436, adult respiratory distress 685, Bartter 329, Bernard-Horner 998, Bouveret-Hoffmann 567, bowel 268, Brown-Séquard 823, carotid sinus 564, chorda tympani 229, Cushing 435, digeorge 118, diuretic-dependent sodium retention, 348, Down 211, Eaton-Lambert 203, Fröhlich 386, 387, 466, 862, inappropriate hypersecretion of ADH, 329, 386, Kallmann 862, Kearns-Sayre 15, Kluver-Bucy 894, Lambert-Eaton 213, myasthenic 65, Liddle’s 37, Lown-Ganong-Levin 568, malabsorption 265, nelson 436, premenstrual 491, Zollinger-Ellison 240, Synonyms of thalamic syndrome 851, Synthesis 415, 426, 462, 790f, of adrenal sex hormones 434f, of aldosterone 426f, of ATP 11, of catecholamines 439, 440f, of cortisol 430f, of eicosanoids 447, of estrogen 477, , of fatty acids 416, of proteins 8, Synthetic, function 255, 267, 355, senses 829, steroids 434, Syphilis 344, Syringomyelia 825, System of genital ducts 473, Systemic, arterial pressure 318, blood pressure 639, circulation 524, 524f, vascular function curves 585, Systole of heart 603, Systolic, blood pressure 441, 603, heart failure 663, hypertension 614, murmur 550, pressure in different age 603, , T, T lymphocytes 98, 108, Tabes dorsalis 344, 825, Tabes dorsalis, cause of 825, Tabetic bladder 344, Table sugar 287, Tachycardia 522, 587, occurs 564, 587, Tachypnea 723, Tactile, discrimination 813f, 814, localization 813f, sensation 814, Tail 472, portion 5, Tangent 988, Tank respirator 750, Target cells 367, Taste 1025, appreciation of 225, blindness 1027, bud 245, 1024, 1025f, center 1025, receptor 1026, cells 1024, sensation 1025f, 1026, sensation, abnormalities of 1027, transduction 1026, Taurin 252, Taurocholate 252, Taurocholic acids 252, Tear 967, Tectal or midbrain outflow 957, Tectocerebellar tract 872
Page 1107 :
1086 Essentials of Medical Physiology, Tectorial membrane 1011, 1012, Tectospinal tract 820, Tectum 845, Tegmentum 845, Telephone, theory of rutherford 1020, transmitter 1020, Telereceptors 775, Temperature 809, different parts of body 359, effects of variations 184f, regulation 51, sensations 810, transducers 579, Temporal, fields 987, lobe 893, syndrome 894, areas and connections of 894t, summation 785f, 786, 800, 801, thalamic peduncle or radiation 850, Temporary, anosmia 1030, endocrine gland 485, Tendon 169, 205, reflexes 797, Tension, developed in muscle 186f, pneumothorax 734, vs overlap of myofilaments 186, Tensor tympani 1009, Teratospermia 472, Teratozoospermia 472, Terminal, bronchiole 674, coils 782, knobs 781, or peripheral ganglia 957, Tertiary, bronchi 674, hyperparathyroidism 404, Test for visual acuity 986, Testes 461, 465, Testes, descent of 463, Testicular cancer 463, Testis, coverings of 456, Testosterone 460, secretion in different periods of life, 462, secretion, regulation of 464, Tests for hearing 1023, Tests, biological 508, Tetanus 181, 182, Tetanus, definition 181, Tetany 403, Tetraplegia 821, 837t, Texture of tissues 51, , TG cells in stomach 282, Thalamic, animal 915, hand 852, lesion 851, nuclei 847, nuclei, connections of 849, nucleus 848f, over-reaction 852, peduncle or radiation 850, peduncle or radiation, Anterior, (frontal) 850, peduncles 849, phantom limb 852, preparation 907, radiations 849, reticular nucleus 848, stalks 849, Thalamic syndrome 851, Thalamohypothalamic fibers 856, Thalamus 847, Thalamus, connections of 849f, Thalassemia 91, 92f, Thawing and gangrene 747, Thebesian veins 630, 678, Theca, externa 484, folliculi 484, interna 484, interna cells 485, Thelarche 510, Theories of, autoregulation 601, color vision 1000, first group 1020, second group 1020, Therapeutic, plasma exchange 63, radiography 581, uses of, anabolic steroids 464, cardiac catheterization 581, Thermal, changes during muscular contraction, 199, sensations 812, Thermistors 579, Thermoanesthesia 810, Thermodilution technique 578, Thermogenic effect 480, 493, Thermogenin 296, Thermoreceptors 361, 720, Thermostatic mechanism 860, Theta waves 930, Thiazide 349, Thick, ascending segment 307, 329, descending segment 307, 329, , Thickness of, cell membrane 29, respiratory membrane 706, Thin ascending segment 307, of henle loop 329, Thin descending segment 307, of henle loop 329, Thiocyanate 398, Thiourylenes 398, Third, degree, heart block 566, of injury 770, heart sound 536, 546, 548, and ECG 546, causes of 546, order neurons 807, 839, 989, 1014,, 1014f, 1025, period of sexual life in females 475, Thirst, center 860, mechanism 860, 861, Thiry, fistula 264, loop 264, vella loop 264, Thomas young trichromatic theory, 1000, Thomsen-type myotonia 212, Thoracic, duct 155, ganglia 955, lid 683, operculum 683, segment 804f, 805f, 819, 820, Thoracolumbar outflow 954, Thorax and abdomen 955, Thready pulse or weak pulse 625, Threshold, for olfactory sensation 1029, for taste sensations 1026, level in plasma 322, substances 321, Throat, cancer 157, infection 157, Thrombasthenic purpura 137, Thrombin 135, time 136, Thrombocythemia 126, Thrombocytopenia 125, Thrombocytopenic purpura 64, 137, Thrombocytosis 125, Thrombolysis 633, Thrombomodulin 132, Thrombophlebitis 147, Thrombopoietin 125, 302, 445
Page 1108 :
Index 1087, Thrombopoietin, action of 445, Thrombosis 137, 524, Thrombosis, causes of 137, Thrombospondin 123, Thrombosthenin 123, Thromboxanes 447, 448, Thrombus 137, 524, Thymin 445, Thymopoietin 445, Thymosin 445, Thymus 135, 445, Thyroglobulin 388, synthesis 389, Thyroid 388, adenoma 395, disorders, treatment for 398, function tests 398, gland 388, 389f, 388f, 502, gland, disorders of 395, hormone-induced thermogenesis 392, hormones 389, 390f, hormones, regulation of secretion of, 394, 395f, Thyroidectomy 403, Thyroiditis 396, Thyroid-stimulating, autoantibodies 395, hormone 40, 380, 394, Thyrotoxic myopathy 393, Thyrotropes 376, Thyrotropic-releasing hormone 377, Thyroxine 75, 388, 610, Thyroxine-binding, globulin 391, prealbumin 391, Tickling of watch test 1023, Tidal volume 691, 691f, 693f, Tight, collar 660, junction 22, 23f, strands 22, Tigroid substances 760, Tilting of myosin head 195f, Timed vital capacity 696, Timing and programming movements, 875, Tiselius apparatus 61, Tissue 3, 708t, 709f, connective 3, epithelial 3, fat 294, fluid 652, 159, fluid, formation of 159, 160f, macrophages 151, 152, muscle 3, nervous 3, plasminogen activator 132f, , resistance work 689, to capillary, diffusion of carbon, dioxide from 708f, Tissues into blood, diffusion of carbon, dioxide from 709, Tissues, changes in 740, Titin 173, TM value 321, TNF- α 18, TNF- β 18, Tolerance 119, Tone, adjustment of 913, redistribution of 913, Tongue 844, Tonic, contraction 342, of muscle 935, of smooth muscle without action, potential 207, receptors 777, stage 935, Tonicity 54, Tonsillitis 157, Torsion 974, Torso 435, Total, blindness 992, circulation time 600, color blindness 1002, iron in body, regulation of 82, lung, cap 691f, capacity 692, 693f, surface area of respiratory, membrane 706, tension 185, Toxemia 822, of pregnancy 614, Toxic, effects of carbon monoxide 733, goiter 397, substances 655, 659, 660, thrombosis 137, Toxins 1002, Toxoids 118, T-PA inhibitor 132, Trabeculae 972, Trachea 674, Tracheal cannula 582, Tracheobronchial tree 674, Tract, absorption from gastrointestinal 406, anterior, spinocerebellar 810, spinothalamic 807, vestibulospinal 818, , burdach 813, cerebello-olivary 872, cerebelloreticular 872, cerebellovestibular 869, cerebropontocerebellar 874, crossed pyramidal 817, cuneocerebellar 871, dentatorubral 874, dentatorubrothalamocortical 874, dentatothalamic 874, gastrointestinal 219, 220f, 931, hypothalamohypophyseal 381, 856, indirect corticospinal 817, lateral corticospinal 817, lissauer 812, mamillotegmental 856, mamillothalamic 856, nerve supply to gastrointestinal 221, pontocerebellar 872, 873, spino-olivary 812, spinoreticular 812, spinotectal 811, spinovestibular 812, tectospinal 820, vestibulocerebellar 869, 923, vestibulo-ocular 923, vestibuloreticular 923, vestibulospinal 923, Tracts, association 807, crossed spinothalamic 823, 825, in spinal cord 806, intrinsic 807, of spinal cord 809f, Tractus solitarius 716, 1025, Trail ending 910, Trans fats 292, Transcellular route 320, Transcription of, DNA to RNA 391, genetic code 16, Transcytosis 36, 952, Transfer RNA 16, Transferrin 82, Transformation B cells 112, Transfusion, of blood 146, reactions 142, 146, 337, cause for 142, to ABO incompatibility 141, to Rh incompatibility 143, Transient receptor potential 777, Translation of, genetic code 16, RNA 391, Transmission of, infections 147, pulse 622
Page 1109 :
1088 Essentials of Medical Physiology, Transmitted waves 576, Transneuronal degeneration 772, Transport, cell membrane 27, from interstitial fluid to blood 322, from lumen of renal tubules into, tubular epithelial cells 322, from tubular cells into interstitial, fluid 322, in blood 480, in plasma 478, maximum 321, mechanism 51, of calcium ions 32, of carbon dioxide 77, 713, from tissues to lungs 68, in blood 714f, of enzymes 60, of hormones 60, of hydrogen ions 32, of iodine into follicular cavity 390, of iron 82, of lipids in blood 291, of neurotransmitter 789, of oxygen 77, 711, from lungs to tissues 68, of respiratory gases 77, 711, of thyroid hormones in blood 391, Transpulmonary pressure 687, Transradial catheterization 580, Transverse diameter of thoracic cage, 683, Trapezoid body 1013, Trauma 1002, Traumatic shock 659, Traveling wave 1018, for different frequencies of sound, 1018f, theory 1021, Treatment for, angina pectoris 633, carbon monoxide poisoning 734, cataract 977, circulatory shock 662, Cushing syndrome 436, diabetes mellitus 424, eclampsia 502, erythroblastosis fetalis 144, gallstone 260, glaucoma 976, hemophilia 136, hyperthyroidism 398, hypothyroidism 398, hypoxia 728, oxygen therapy 728, Parkinson disease 883, thyroid disorders 398, , Treatment of, hypertension 615, mountain sickness 739, Trehalase 287, Tremor 393, 882, Treppe 183, Tricarboxylic acid cycle 198, Trichromatism 1003, Tricuspid, area 548, valve 522, Trigeminal lemniscus 832, Trigeminocerebellar tract 872, Triglycerides 416, Trigone 339, Tripeptidases 291, Triple, and quadruple heart sounds 547, heart sound 546, 547, response 647, Tritanomaly 1003, Tritanopia 1003, Tritium oxide 53, Trochlear nerve 973, Trophoblastic, cells 499, cords 499, Tropic hormones 377, Tropical, sprue 265, Tropomyosin 173, Troponin 173, Trousseau sign 404, True, capillaries 641, diabetes mellitus 378, Trypsin 242, 291, actions of 243, inhibitor 243, T-tubules 174, Tubectomy 515, Tuber cinereum 991, Tubular, maximum for glucose 323, myelin 684, necrosis 334, 337, portion of nephron 306, reabsorption 319, 324, reabsorption, regulation of 320, secretion 323, 324, structures of kidney 303, Tubulin 12, Tubuloglomerular feedback 311, 314,, 317, 318f, Tumor, cells 387, metastasis 25, necrosis factors 116, , Tunica, adventitia 523, albuginea 456, 476, externa 967, fibrosa 967, media 523, 968, nervosa 969, vaginalis 456, vasculosa 456, 968, Tunnel of corti 1012, Turbulence 550, Turbulent 549, flow 596, 596f, Turner’s syndrome 15, Tympanic, membrane 1008, 1009f, reflex 1009, wall 1011, Tympanum 1008, Type I hair cells 921, Type I or anaphylactic reactions 120, Type II hair cells 921, Type II or cytotoxic reactions 121, Type III or antibody-mediated reactions, 121, Type IV or cell-mediated reactions 121, Type of cells in taste bud 1024, Type V or stimulatory 121, Types causes of purpura 137, Types myotonia 212, Types of, acquired immunity 107, active transport 31, 33, Addison disease 437, antibodies 113, antigen-presenting cells 110, astigmatism 1005, atrophy 19, auditory defects 1022, axon terminals 781, B lymphocytes 108, blood flow 596, buffer systems 43, calcium 405, cell adhesion molecules 26, cells in bone 410, chemoreceptors 720, chromaffin cells 376, 439, circulatory shock 659, compliance 687, conduction 178, 1017, cytokines 115, dead space 701, defensins 116, diuretics 348, edema 160, endoplasmic reticulum 7
Page 1110 :
Index 1089, epilepsy 935, exercise 664, glaucoma 976, heart failure 663, hemianopia 136, 992f, hemorrhage 651, hyperaldosteronism 436, hypertension 614, hypotension 615, hypoxia 727t, 729, interferons 116, interleukins 116, intrafusal fibers 909, jaundice 258, 259t, lung function tests 690, lymphocytes 98, lysosomes 9, molecular motors 36, movements of small intestine 277, muscle strength 214, nephron 305, 305f, 305t, nerve fibers 765t, neuromodulators 792, neuron 760f, non-self antigens 110, normal hemoglobin 78, osmosis 31, paralysis 837, 837t, passive transport 30, pneumonia 734, prostaglandins 447, protein channels 28, refractory period 769, respiration 673, ribosomes 11, rigors 183, RNA 16, sleep 932, smooth muscle fibers 205, somatic sensations 828, somatomedin 379, stem cells 21, stimulus 176, 179, strength 179, stroke 637, syncope 660, T lymphocytes 108, vasogenic shock 660, Typical circulation times 600, Tyrosine 389, 439, derivatives 372, kinase 417, , U, U wave 556, Ulcer 289, , Ulcerative colitis 269, Ultracentrifugation method 62, Ultrasonic, Doppler flowmeter 576, Doppler transducer 579, vibrations 977, waves 576, Ultrasound 576, scanning 493, Ultraviolet, light therapy 147, rays 354, 739, 999, from the sunlight 401, Umami 1026, Umami receptor 1027, Umbilical veins 648, Unconditioned reflexes 228, 236, 796, Unconsciousness 424, Uncontrollable sleep 934, Uncrossed, fibers 811, pyramidal tract 817, Undescended testes 463, Unilateral labyrinthectomy 927, Unilocular 295, Uninhibited neurogenic bladder 344, Unipolar, chest leads 553, leads 553, limb leads 553, neurons 759, Uniport 31, Unit membrane model 5, Universal donors 141, Unmyelinated nerve fibers 381, Unprotonated substance 43, Unsaturated fats 292, Upper, cervical segments 818, costal series 683, esophageal sphincter 271, fields 987, lumbar segments 811, motor neuron 799, 836, lesion 802, 824, respiratory tracts 674, Upregulation 372, Urea, clearance 347, test 336, recirculation of 326, Uremia 338, 347, Uremia, common features of 338, Urethra 339, 456, 466, Urethral sphincters 340, Uric acid 47, 335, Urinalysis 333, , Urinary, bladder 339, bladder, filling of 342, output 315, system 302f, Urine 509, acidification of 330, composition of 333, concentration 328, formation 315, 324, properties of 333, Uriniferous tubules 303, Urobilinogen 254, 335, Urogenital diaphragm 340, Urokinase plasminogen activator 132,, 132f, Use of pavlov pouch 235, Uses of, bickel pouch 235, cardiac catheterization 580, ECG 551, electromyogram 210, farrel and IVY pouch 235, heart-lung preparation 582, heidenhain pouch 235, heparin 133, indicator dilution method 53, lumbar puncture 951, Müeller maneuver 619, plasmapheresis 64, valsalva maneuver 619, Uterine, changes menstrual cycle 486, 486f, changes, regulation of 490, Uterine milk 499, Uterus 474, 500, abnormalities of 496, action on 383, changes in 475, divisions of 474, Utilization, of energy 688, time 177, Utriculosaccular duct 920, , V, V leads or precardial chest leads 553, V wave 628, V wave, abnormal 628, Vaccines 118, Vacuum aspiration 515, Vagal, apnea 724, escape, cause for 590, escape, effect of 590, fibers 1025
Page 1111 :
1090 Essentials of Medical Physiology, stimulation on Frog heart, effect of, 590f, tone 590, withdrawal 666, Vagina 475, 500, during menstrual cycle 487, Vaginal changes during menstrual cycle, 488, Vagovagal reflex 237, 238f, 282, Vagus nerve 235, Valsalva, experiment 619, maneuver 619, 685, maneuver vs Müeller maneuver, 619t, maneuver, effects of 619, Values, belong to adults 406f, of lipid profile 297t, Valves of heart 522, 522f, Valves, atrioventricular 522, Valvular, diseases 549, factor 545, insufficiency 550, leaflets 545, Vanillylmandelic acid 440, Variable region 114, Variation in, anion gap 47t, blood, pressure 603, volume 148, body temperature 360, cardiac output 573, chronaxie 177, coronary arteries 629, differential leukocyte count 99, ESR 84, latent period 179, lung compliance 688f, number of red blood cells 68, PCV 86, plasma protein level 64t, 65, shape of red blood cells 70, size of red blood cells 70, structure of red blood cells 70, temperature, effect of 183, venous pressure 617, ventilation-perfusion ratio 702, vital capacity 696, white blood cell count 99, Varicose vein, causes for 644, in obesity 645, in pregnancy 645, Varicose veins 644, , Vas, deferens 456, 457, 468, efferens 457, recta 313, 327, Vascular, factor 545, functions, coupling of 585, resistance 680, of pulmonary blood flow 680, response 431, of skin to mechanical stimuli 646, spasm 502, Vasectomy 515, Vasoactive intestinal, peptide 236f, polypeptide 238, 284, 611, Vasoconstriction 127, Vasoconstrictor, area 588, 606, fibers 606, Vasodilator, area 588, 606, drugs 633, fibers 606, of endothelial origin 612, of metabolic origin 612, Vasogenic 661, shock 660, shock, types of 660, Vasomotor, center 588, 606, 844, 858, center, areas of 588, tone 606, Vasopressin 610, Vasopressor action 382, Vasopressor effect 610, Vasovagal syncope 660, 661f, Vector 558, cardiogram 561, Vectoral analysis 561, Vegetarian diet 287, Vegetative functions, control of 905, Vein, pulmonary 583, Veins 524, Veins, anterior coronary 630, Velocity of, blood flow 641, blood flow, definition of 598, impulse 765, transmission of pulse 623, Vena cava, inferior 583f, 650f, superior 583f, 650f, Venous, admixture 679, blood 711t, drainage 630, , pressure 575, 617, definition and normal values, of 617, in extremities of body 617, pulse 627, pulse, abnormal 628, reservoir 582, return 574, 666, 821, curve 585, 586f, directly proportional to 605, on arterial blood pressure 605f, system 313, 523, Ventilation 700, method 750, perfusion ratio 702, perfusion ratio, definition of 702, Ventilator 750, Ventral, cochlear nuclei 1013, parabrachial 718, posterolateral nucleus of thalamus, 809, 810, 813, respiratory group of neurons 717, spinocerebellar tract 810, 871, Ventricle, left 650f, right 650f, Ventricular, diastole 534, events 534, description of 535, of cardiac cycle 535f, extrasystole 567, fibrillation 569, hypertrophy 20, musculature pacemaker 569, musculature, depolarization of 554, paroxysmal tachycardia 568, systole 534, 628, volume, changes cardiac cycle 541, 542f, curve 542, Vermis 863, Vertigo 927, Very-low-density lipoprotein 294, 295, Vesicular follicle 483, Vestibular, apparatus 869, division of vestibulocochlear nerve, 922, membrane 1010, 1011, nuclei 844. 922, Vestibulocerebellar tract 869, 923, Vestibulocerebellum 865, 869, Vestibulo-ocular reflex 923, 925, Vestibuloreticular tract 923, Vestibulospinal tract 923
Page 1112 :
Index 1091, Vibratory sensation 813f, Videodensitometry 630, Vipers snakes 135, Viral, hepatitis 259, hepatitis, causes of 259, Virilism 438, Virilism, adrenal 436, Visceral, layer of bowman capsule 316, or autonomic, nerve fibers 764, reflexes 797, or vegetative functions 758, organs 797, 955, pain 840, pain, causes of 840, reflexes 797, sensations 829, smooth muscle fibers 205, Visceroceptors 776, Viscosity 636, of blood 85, 597, 599, 605, Visible spectrum 999, Vision, acuity of 985, binocular 987, bright light 980, monocular 987, Visual, acuity 985, 990, axis 966, 966f, cortex 991, cortex, areas of 895, 991, defects 993f, disturbances 384, evoked potential 897, field 988, field, divisions of 987, 988f, pathway 989, 990f, process 978, process, chemical basis of 980, receptors 979, 989, 004, Vital, capacity 691, 691f, 693f, 696, functions 844, organs 601, Vitamin, A 969, 980, 985, B 75, B12 75, C 75, D 75, 302, D, activation of 401, 401f, deficiency 392, E 75, metabolism, action on 392, , Vitamins 75, 76, Vitamins, absorption of 264, Vitreous humor 971, Vitronectin 123, Vocalization 675, Volatile, acids 43, gas 676, Volkmann canal 410, Volley theory 1020, Voltage clamping 767, 768f, Voltage-gated channels 28, Volume, changes 534, conductor 551, of air flows 690, of blood, flow 598, 605, 641, in left ventricles 542, in right ventricles 542, of venous blood 618, ventilator 750, Voluntary, apnea 724, control 342, effort 724, movements 817, 835, movements, regulation of 880, muscle 167, Vomeronasal, organ 1028, in human beings 1028, receptors 358, Vomeropherins 1028, Vomiting 276, 502, act of 276, causes of 276, center 844, reflex 276, Vomitus 276, von Willebrand, disease 137, factor 123, 124, , W, Waddling gait 414, Wakefulness 860, center 860, Wald visual cycle 980, 981f, Walk along theory 195, Wall of, aorta 607, eyeball 967, 969f, gastrointestinal tract 220, Wallerian degeneration 770, 771, Warfarin therapy 136, , Warm temperature 183, Warm-blooded 178, Warm-blooded animals 359, Warming glass coil 582, Wasted, air 701, 702, blood 679, 702, ventilation 701, Water 501, absorption of 264, balance, regulation of 60, 226, 860, chamber 692, channel proteins 382, hammer pulse 626, intoxication 56, metabolism 431, pills 348, regulation of 355, Watery sweat 357, Waves, in jugular pulse tracing,, abnormalities of 628, of EEG 929, of electroencephalogram 930f, of electroretinogram 985, of normal ECG 553, 554f, 555f, Waxing and waning, causes for 731, of breathing 731, WBCs See also white blood cells 97, Weber test 1023, Weber-Fechner law 777, Weber-Fechner law, derivation of 777, Wenckebach, phenomenon 566, syndrome 566, Westergren, method 83, tube 83, 84f, Wharton duct 223, Wheal 647, Wheat 290, Wheel movements 974, Whether somatic 797, Whipple’s experiment 63, Whispering test 1023, White, adipose tissue 295, blood cells 97, 334, different 98f, properties of 101, buffy coat 86, fat 295, matter of, cerebellum 868, spinal cord 806, pulp 153, reaction 647
Page 1113 :
1092 Essentials of Medical Physiology, Whole-cell patch 194, Wilson disease 883, Windkessel, effect 598, vessels 598, Wings of butterfly 804, Wintrobe, method 83, tube 83, Wirsung duct 241, Withdrawal, of positive signals 17, reflexes 796, Wolffian duct 462, Wolff-parkinson-White syndrome 545,, 568, Woman’s sexual life 494, Womb 474, , Work, done by the muscle 185, 186f, of breathing 688, 689f, Worn-out organelles, degradation of 8,, 10, Writing on skin 647, , X, X wave 628, X wave, abnormal 628, X1 wave 628, Xerostomia 229, Xerostomia, causes 229, , Y, Y wave 628, , Y wave, abnormal 628, Yellow, body 485, spot 971, Yellowish pigment 485, Young-Helmholtz theory 995, YPES of movements of large, intestine 278, , Z, Zero potential 191, Zollinger-Ellison syndrome 240, Zonula, adherens 25, occludens 22, Zygote 484, Zymogen granules 234
