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The Urinary System, , rid body of CO2 from energy metabolism of cells, 4. liver, liver excretes bile pigments, salts, calcium, some toxins, , Urine production and elimination are one of the most, important mechanisms of body homeostasis, , 2. elimination of excess nutrients & excess hormones, , all body systems are directly or indirectly affected by, kidney function, , 3. helps to regulate blood volume & pressure, blood pressure is directly affected by the volume of fluids, retained or removed from body:, , eg. composition of blood is determined more by kidney function, than by diet, , eg. excessive salts promote water retention, greater volume ! increases BP, , main function of kidneys is to get rid of metabolic, wastes, , eg. dehydration, lower volume ! decreases BP, , !typically referred to as “excretory system”, , 4. regulation of electrolytes & body pH, , excretory wastes = metabolic wastes, , 5. regulates erythropoiesis, , ! chemicals & toxins produced by cells during, metabolism, , kidneys produce hormone = erythropoietin that regulates, erythropoiesis:, , General Functions of Urinary System:, , hypoxic ! secretes more erythropoietin, excessive O2 inhibits hormone production, , 1. removal of metabolic wastes & toxins, , 6. aids in calcium absorption, , but we have several organs that serve an excretory function, other than kidneys:, , affects the absorption of Calcium from intestine by helping to, activate Vitamin D circulating in blood, , 1. kidneys, 2. skin, sweat glands rid body of water, minerals,, some nitrogenous wastes (ammonia), 3. lungs, Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 1, , Anatomy of Urinary System, Organs:, kidneys, ureters, bladder, urethra, , –, –, –, –, , Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , extensions of the cortex = renal columns, divides the medulla into 6-10 renal, pyramids, , clean and filter blood, tubes that take urine to bladder, stores urine until eliminated, removes urine from body, , papilla of each pyramid nestled in cup shaped, calyces, calyces converge to form renal pelvis, , 1. kidneys, , 2. ureters, , dorsal body wall, , the rest of urinary system is “plumbing”, , retroperitoneal ! behind parietal peritoneum, just above waist, , renal pelvis funnels urine to paired ureters, !tubular extensions of renal pelvis, , surrounded by renal capsule, , peristalsis moves urine along to bladder, 3. bladder, , ! barrier against trauma and spread of, infections, , small, size of walnut when empty, , hilum = indentation where vessels and ureter, attach, , can hold up to 800 ml (24 oz) voluntarily, up to 2000 ml (60 oz) when obstructed, , wall consists of 4 layers, , Frontal Section of Kidney, , mucosa, , cortex, outer zone of kidney, , (same as GI tract), , -innermost layer, secretes mucous for protection from, corrosive effects of urine, , medulla, interior of kidney, Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 2, , submucosa -fibrous connective tissue, 3, , Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 4

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Histology of Kidney, , muscularis -several smooth muscle layers, serosa, , -visceral peritoneum, , nephron = functional units of kidneys, each kidney is composed of over 1 million nephrons, , involuntary internal & voluntary external, urethral sphincters, , two basic parts:, , as bladder expands to hold urine, , 1. nephric tubule, = microscopic, highly convoluted tubule, , ! activates stretch receptors in wall that, monitor volume, , 2. associated blood supply, can find various parts of the nephron and its blood supply in the, cortex and medulla of kidney, , ! when volume exceeds 200 ml the receptor, signals enter our conscious perception, = desire to urinate, , Nephric Tubule, , 4. urethra, , the nephric tubule is organized into several discrete, structures:, , male:, , Bowman’s Capsule, , dual function:, , cup shaped mouth of nephron, usually in cortex, , ! rid body of urine, ! release of seminal fluid during orgasm, , Proximal Convoluted Tubule, attached to Bowman’s Capsule, highly coiled (convoluted), inner surface contains microvilli, , female:, single function: rids body of urine, , Loop of Henle, large loop consisting of:, descending limb & ascending limb, extends down into medulla, , shorter, ! more prone to UTI’s, Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 5, , Distal Convoluted Tubule, , Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 6, , !branches eventually into afferent arterioles, , appears similar to PCT, , Afferent Arteriole, , Collecting Tubule, , bring blood to individual nephrons, , many DCT’s drain into one collecting tubule, bundles of collecting tubules = pyramids, , Glomerulus, , Pyramids drain into Calyces (sing. = calyx), , dense capillary bed, formed by afferent arteriole, inside Bowman’s capsule, , Calyces coalesce to form pelvis, , Bowman’s Capsule + Glomerulus = Renal Corpuscle, , Efferent Arteriole, , Blood Supply, , blood leaves glomerulus via efferent arteriole, [! artery!capillary bed! artery], , kidneys are highly vascularized, , Peritubular Capillaries, , every minute, 1200 ml/min of blood flows through, kidneys, , efferent arteriole divides into another capillary bed, surrounds the rest of the nephric tubule, (PCT-LH-DCT-CT), , !=1/5th of cardiac output, , Renal Vein, returns blood to vena cava, , 45 gallons/day; all blood ~60x‘s/day, , more blood perfuses the kidney per weight than any, other organ, (much more than eg. brain, heart, liver, etc), within the kidney, bloodflow is greatest in the cortex where, glomeruli are located; flow decreases with depth in the, medulla, , Renal Artery, brings blood to kidney, Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 7, , Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 8

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Urinary Physiology, , kidneys can maintain a fairly constant filtration rate, ! changes in arterial pressure from 80 to 180 mmHg produce, little change in blood flow and filtration rate in glomerulus, , urine formation in nephrons occurs by:, 1. filtration, 2. reabsorption, 3. secretion, , if blood pressure is reduced below this urine, formation slows down, filtrate is essentially the same composition as plasma, without formed elements or proteins, , 1. Filtration, occurs in renal corpuscle:, Glomerulus, , !, , solutes (filtrate) enter Bowmans capsule, , Bowmans Capsule, , 2. Tubular Reabsorption, , water, salts, small molecules and wastes are filtered, out of blood, , urine is not the same composition as this filtrate, Composition of Plasma, Filtrate & Urine, , capillaries of glomerulus:, , (solids in grams/24hrs; water in liters/24 hrs), , fenestrated capillaries, ! act like sieve, , Plasma, Proteins, Glucose, Salts, Water, Urea, Uric Acid, Creatinine, , molecules less than 10,000MW, , have higher filtration pressure than other, capillaries of body, afferent arteriole is larger than efferent arteriole, , 8,000, 180, 1,498, 180, 50, 8, 1.5, , Filtrate, 15, 180, 1,498, 180, 50, 8, 1.5, , Reabsorbed, Amount, %, 15, 100.0%, 180, 100.0%, 1,486, 99.1%, 178, 99.2%, 25, 50.0%, 7.2, 90.0%, 0, 0.0%, , Urine, 0, 0, 12, 1.5, 25, 0.8, 1.8, , most of the filtrate is reabsorbed, overall, ~99% of glomerular filtrate gets reabsorbed, !only ~1% of original filtrate actually leaves the, body as urine, , ! increases pressure in glomerulus, pressure ~55mmHg, (vs 35mmHg in most capillaries), , !reabsorption is more selective, 9, , Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , needed nutrients are conserved, wastes and toxins are eliminated, blood levels of fluids, salts, acidity etc are actively regulated, , Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 10, , all small proteins, glucose, amino acids are, reabsorbed, most water, most salts are reabsorbed, , main metabolic wastes removed by kidneys are, “nitrogen wastes”:, 1. urea, 2. uric acid, 3. creatinine, , Loop of Henle, additional Cl+ and Na+ ions are reabsorbed by, active transport, , 1. urea, main nitrogen containing waste produced during metabolism, formed in liver as result of protein breakdown, concentration in urine mainly determined by dietary intake\, , under the control of aldosterone, (mineralocorticoids), secretion controlled by salt, concentrations in tissue fluids, , 2. uric acid, end product of nucleic acid metabolism, some is also secreted by PCT, , also affects reabsorption of water, (water follows salt), , 3. creatinine, normal end product of muscle metabolism, , Distal Convoluted Tubule & Collecting Tubule, , occurs all along nephric tubule, , additional water is reabsorbed, , but different substances are reabsorbed back into, blood from different parts of tubule:, , under control of ADH (antidiuretic hormone), , Proximal Convoluted Tubule, , No ADH ! tubules are practically, impermeable to water, , ~80% of materials to be reabsorbed are, reabsorbed in PCT, , with ADH ! tubules are permeable to, water, , cells lining PCT have, microvilli, Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 11, , Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 12

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Urine Analysis, , 3. Tubular Secretion, cells of DCT and CT can also actively secrete, some substances, , the kidneys perform their homeostatic functions of, controlling the composition of internal fluids of, body, , esp K+ and H+ HCO3 NH4, some drugs (eg. penecillin), , the by-product of these activities is Urine, , usually urine is slightly acidic, , urine contains a high concentration of solutes, , ! normal diet produces more acid than alkaline waste, products, , in a healthy person, its volume, pH and solute, concentration vary with the needs of body, during certain pathologies, the characteristics of urine, may change dramatically, an analysis of urine volume, physical and, chemical properties can provide valuable, information on the internal conditions of the, body, Physical Characteristics, eg. Volume, normal = 1000 – 1800ml/day (2-3.5 pints), influenced by:, blood pressure, blood volume, temperature, diuretics, mental state, , Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 13, , general health, , Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 14, , pus from infections, , eg. Color, , Chemical Characteristics, , normal = yellow-amber (from hemoglobin breakdown), , eg. proteins, , influenced by:, ratio of solutes, ! >solute conc., = darker yellow to brownish, ! <solute conc., = less color to colorless, diet (eg. beets), blood in urine, , normally too large to filter out, presence indicates increased permeability of glomerular, membrane due to:, injury, high blood pressure, irritation, toxins, , eg. glucose, , eg. pH, , normally, all is filtered and all reabsorbed, body reabsorbs as much as is needed, , normal urine is slightly acidic: 5.0 - 7.8, influenced by:, diet, , when it appears in urine indicates high blood sugar, concentrations, ! symptom of diabetes mellitis, , eg. high protein ! acidic, vegetables ! alkaline, metabolic disorders:, eg. lungs, kidneys, digestive system, etc, , eg. ketones, produced when excessive quantities of fats are, being catabolized, , eg. Cells and Castings, , high quantities may be caused by:, diabetes, starvation, dieting, !too little carbohydrates in diet, , normally find epithelial cells and some bacterial cells, Bacteria, < 100-1000/ml = contamination by normal flora, >100,000/ml = indicates active colonization of urinary, system, RBC’s & WBC’s, presence is almost always pathological, inflammation of urinary organs, Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 15, , Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 16

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The Aging Urinary System, , older women become increasingly subject to, incontinence, ! esp if pelvic wall muscles have been, weakened by pregnancy and childbearing, , kidneys show lots of atrophy in old age, ! from ages 25 to 85; number of nephrons, declines by 30 – 40%, ! up to 1/3rd of remaining glomeruli become, atherosclerotic, bloodless and nonfunctional, , incontinence can also result from senescence of, sympathetic NS, , kidneys of 90 yr old man are 20 – 40% smaller than, those of a 30 yr old and receive only half as much, blood, proportionately less efficient at clearing wastes, ! while renal function remains adequate there is, little reserve capacity, reduced renal function is a significant factor in, overmedication of the aged, !drug doses often have to be reduced, water balance is more difficult, ! kidneys become less responsive to ADH and, sense of thirst is blunted, voiding and bladder control become problematic:, ~80% of men over 80 are affected by benign, prostatic hyperplasia that compresses the, urethra, ! reduces force of urine stream, ! makes it harder to empty bladder, Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 17, , Disorders of Urinary System, , Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 18, , form in renal pelvis, , Acute or Chronic Renal Failure, (or renal insufficiency), , usually small enough to pass into urine flow, , most serious disorder of urinary system, nephrons can regenerate and restore kidney function after shortterm injuries or individual nephrons can enlarge to, compensate, ! a person can survive with as little as 1/3rd of one, kidney, when 75% are lost the remaining cannot maintain homeostasis, , sometimes are up to several centimeters and block pelvis or \, ureter, ! leads to destruction of nephrons as pressure builds, in kidney, a large, jagged stone passing down ureter can stimulate strong, contractions that can be excruciatingly painful, can also damage ureter and cause hematuria, causes:, hypercalcemia, dehydration, pH imbalances, frequent UTI’s, enlarged prostate causing urine retention, , result is azotemia and acidosis, may also lead to anemia, , Cystitis (=bladder infection), , (largest stone on record: 3 lbs 16” x14” in body cavity), , most are ascending infections! move up urethra from outside, especially common in women, if untreated bacteria can spread up ureters to cause pyelitis or, infection of pelvis, if infection reaches renal cortex and nephrons = pyelonephritis, kidney infections can also result from invasion by blood borne, pathogens (=descending infection), , Kidney Stones, =Renal Calculus is a hard granule of calcium, phosphate, uric acid, and protein, Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 19, , Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 20

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Fluid & Electrolyte Balance, , output is crucial element in control of fluids and, electrolytes, , body is ~2/3rds water (males=63%; women=52%), , most important output organ is kidney, , balance means: input = output, , major control of urine volume is reabsorption of water, , Inputs, 1. digestive tract: food and drink, , reabsorption can be controlled to make output match, input, , food ~1200ml/d; beverages ~1000ml/d, , controlled by two major hormones:, , 2. metabolism: each cell produces water in, catabolism of glucose, , ADH, Aldosterone, , 250-300ml/d, , additional factors that can affect fluid loss:, , Outputs, , 1. urine volume can also be affected by amount of, solutes in urine, , 1. urine (kidneys), main loss, ~1500ml/d, , ! the more solutes the more urine, , 2. lungs: water vapor expired with air, , Diabetes mellitis, excess glucose spills over into urine, causes excess water to enter nephric tubule by, osmosis, results in excessive water loss & dehydration, , at rest skin and lungs loose ~900ml/d, , 3. sweat (skin), in hot environment with vigorous exercise can lose up to, 4L/h, , 2. hyperventilation, , 4. feces (intestines), , over extended time can lose significant, water from lungs, , normally small losses, ~100ml, Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 21, , may result in dehydration, , 22, , eg. dehydration, , 3. excessive sweating, up to 4L/hour, , output > input, caused by:, excessive sweating, water deprivation, chronic diarrhea, excessive vomiting, , 4. prolonged vomiting or diarrhea, Electrolyte Composition of Fluids, fluids in the body contain critical electrolytes and other, solutes:, cations: Na+; Ca++; K+; Mg++, anions: Cl- ; CHO3- ; HPO4- -; Proteins, , eg. athletes can lose up to 4l of water/hour, but can only safely take in ~2l/hr, Blood loses water ! ECF loses water ! cells lose, water, , These electrolytes function:, , infants & elderly more likely to suffer dehydration, since their kidneys are less able to conserve, water, , 1. essential nutrients or building blocks, 2. serve critical role in regulation of various, metabolic pathways, , treatment: replace water and lost electrolytes, , 3. affecting membrane potentials of muscle and, nerve cells, , eg. water intoxication, , 4. control water movement between, compartments by affecting osmotic pressures, 5. help to regulate pH of body fluids, Water Balance Disorders, Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , input > output, often happens after dehydration, ! water is taken in too quickly without, electrolytes, input ! to blood ! to tissue spaces ! to cells, , 23, , Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 24

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Acid/Base Balance, can cause edema as water collects in ISF, causes cells to swell as it moves from tissue spaces, into cells, especially affects cells sensitive to ion, concentrations: muscle and nerve cells, , some of most critical ions in body fluids are H+, (hydrogen) and OH- (hydroxyl) ions, the concentrations of these two ions affect the acidity, or alkalinity of body fluids, acidity/alkalinity is measured on pH scale, 1pH unit = 10 fold change in [H+], pH of 7 is neutral, pH < 7: more H+, fewer OHpH > 7: fewer H+, more OH-, , can result in:, heat cramps, convulsions, confusion, coma, , large organic molecules, especially proteins, are, extremely sensitive to changes in pH, ! easily denatured, , eg. edema, =abnormal accumulation of water in ECF, , since proteins serve a wide variety of roles in the body, (enzymes, fibers, carriers, hormones, oxygen transport,, immunity, etc), , caused by:, decreases in plasma proteins due to, liver disease, kidney disease, starvation, obstruction of lymphatic vessels, increased venous pressure, increased capillary permeability, eg. inflammation, sunburn, , variations in pH affect almost every aspect of, physiology and cell metabolism, even slight changes in pH can be fatal, blood = 7.35 – 7.45, !7 or "7.8 is fatal, , various acids and bases continually enter and leave, body:, in foods and drink, gastric secretions, bicarbonates from pancreas, , Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 25, , etc, , Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , pH =, , acids and bases are also made as a normal part of, metabolism:, , buffers act by combining with strong acids or bases and, taking them out of solution, ! “absorbs” the H or OH ions, , waste products like CO2 and ammonia are turned into acids, in the blood, , body is protected against large changes in pH in two, step process:, , all buffers have limited capacity, , 1. buffers, , – absorb excess hydrogen or hydroxyl ions to, prevent drastic changes in pH, , !buffering alone cannot maintain homeostasis, indefinitely, , – acids (or bases) are removed, , at some point the acids and bases must actually be, removed from the body, , from body by:, , skin, , - can secrete H+ and HCO3– as CO2 is eliminated H+ are converted, to water, – can excrete some acids in sweat, , two main removal systems:, 1. Respiratory Mechanisms, 2. Excretory Mechanisms, , Buffers, a buffer is a substance that prevents marked changes, in pH of a solution when acids or bases are added, , Respiratory Mechanisms, respiration plays vital role in removing excess acids, , eg. 1 drop of HCl in pure water, pH =, 7, 3.5, , with each expiration, CO2 and therefore H+ are, , 1 drop of HCl in plasma, Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , major buffers in body fluids:, bicarbonate, phosphate, hemoglobin, plasma proteins, , need some mechanism to neutralize them:, , kidneys, lungs, , 7.27, , ! blood is buffered, , breakdown of proteins, carbohydrates lipids and nucleic, acids produce acids: amino acids, fatty acids, pyruvic, acid, etc, , 2. elimination, , 7.41, , 26, , 27, , Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 28

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removed, carbonic anhydrase, , CO2 + H2O, , H2CO3, , H+ + HCO3-, , pH receptors in arteries can increase or decrease, respiratory rate based on buildup of acids in blood, acidosis ! stimulates hyperventilation, Excretory Mechanisms, cells of DCT and CT can secrete H+ & HCO3-, , symptoms:, labored breathing, cyanosis, depression of CNS ! drowsiness,, disorientation, coma ! death, can be compensated for by kidneys, , if blood pH decreases below normal levels tubules will, increase secretion of H+, , b. Metabolic Acidosis, accumulation of non-respiratory acids or, excessive loss of bases, eg. poor kidney function, prolonged diarrhea, severe vomiting ! loss of duodenal fluids, diabetes mellitis ! ketone bodies are acidic, , more efficient mechanism than respiratory system, usually urine is slightly acidic, ! normal diet produces more acid than alkaline waste products, , Acid/Base Imbalances, , 2. Alkalosis, !accumulation of excess bases, !excessive loss of acids, , 1. Acidosis, ! accumulation of excess acids, ! excessive loss of bases, , a. Respiratory Alkalosis, caused by hyperventilation, , a. Respiratory Acidosis, hypoventilation; factors that cause buildup of, CO2 in blood, generally due to factors that hinder pulmonary, ventilation, Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , may also be caused by strokes, meningitis and, brain tumors, , 29, , fever, inflammation and severe liver, disease, some poisonings, hyperventilation sometimes accompanies, pulmonary diseases such as asthma,, pulmonary edema, and pulmonary, embolism, maternal hyperventilation often occurs, throughout pregnancy possibly caused, by effects of hormones on CNS, , hyperventilation causes too much CO2 to be, ventilated causing an increase in pH, anxiety, 30, , Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , Summary of Acid-Base Homeostasis, Acids produced, by Metabolism, , Acids produced, by respiration, , Acids in, foods and drinks, , Excessive loss or, gain of acids or bases, , Buffers, , many underwater swimmers have died when they, hyperventilated to try to prolong their time, underwater, , [bicarbonates; phosphates; proteins], , Acids and Bases combine with chemical buffers to prevent harmful changes in pH and, allow time for lungs and kidneys to remove them, , symptoms:, light headedness, agitation, tingling, dizziness, b. Metabolic Alkalosis, caused by:, gastric drainage (lavage), prolonged vomiting of stomach contents, too many antacids, , Breathing Rate, , Tubular Secretion, , stimulated by CO2 & H+ ions, , secrete excess H+ or HCO3- into urine, , regulates CO2 in plasma, , regulates pH of blood, , Acid/Base Homeostasis, , Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 31, , Human Anatomy & Physiology: Urinary System; Ziser Lecture Notes, 2010.5, , 32