Urinary System I. Kidneys A. Anatomy 1. External Anatomy (Review Anatomy) a. Kidneys are retroperitoneal b. Right kidney is lower due to liver c. Terms: (1) renal capsule, renal adipose capsule, hilum (small amount) 2. Internal Anatomy a. Gross structures: (1) Cortex (2) Medulla (3) Renal pyramids (a) Medullary rays - extend from pyramids into cortex (b) Renal column - extension of cortex between pyramids (c) Renal papillae - tip of pyramid (4) Minor and Major calyces (5) Renal pelvis (6) Ureter b. Microscopic structures of kidney (1) Nephron - basic functional unit of the kidney (a) Consists of renal corpuscle, proximal convoluted tubule, loop of Henle (nephron loop), distal convoluted tubule. (b) 1,300,000 nephrons / kidney (c) 1/3 must be functional for survival (2) renal corpuscle - enlarged end of nephron (a) glomerulus - network of capillaries. i) fenestrae (windows) ii) Afferent arteriole - supplies blood to glomerulus iii) Efferent arteriole - drains glomerulus (b) Bowman’s capsule - surrounds the glomerulus i) parietal layer - outer layer simple squamous epithelium ii) visceral layer - inner layer made of podocytes iii) fenestrae - openings in capillary walls. iv) filtration slits - between the podocytes surrounding capillaries (c) Filtration membrane

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i) composed of capillary endothelium (with fenestrae), basement membrane, podocytes (with filtration slits) ii) urine passes from capillary to lumen of Bowman’s capsule (3) juxtaglomerular apparatus (a) juxtaglomerular cells - smooth muscle cells form a cuff around the afferent and efferent arteriole (b) macula densa - specialized cells in portion of distal convoluted tubule in contact with the afferent arteriole / juxtaglomerular cells. (4) Proximal convoluted tubule (a) simple cuboidal epi. (b) contain microvilli on luminal surface (5) Loope of Henle (nephric loop) (a) desending limb i) similar in structure to proximal tubule ii) thin near end iii) change form simple cuboidal to simple squam. (b) ascending limb i) transition form simple squamous to simple cuboidal (6) Distal Convoluted tubule (a) simple cuboidal with no microvilli (7) Collecting ducts (a) simple cuboidal (b) extend through the medulla to papillae. 3. Arteries and Veins a. Renal artery b. segmental a. c. interlobar - within renal columns d. Arcuate a. - across base of pyramid e. Interlobular a. - project into cortex. f. Afferent a. g. Glomerulus h. Efferent a. i. Peritubular capillaries - around proximal and distal convoluted tubules (1) vasa recta - enter medulla along with loops j. Interlobular v. k. Arcuate veins l. Interlobar veins 2

m. Renal vein 4. Ureters and urinary bladder a. Ureters - extend inferiorly from kidney from renal pelvis b. Urinary bladder (1) muscular container. (2) size depends on presence of urine (3) Trigone - triangular area between two ureters and urethra (4) Urethra (a) internal urinary sphincter - smooth muscle (b) external urinary sphincter - skeletal muscle II. Urine Production Nephron is the functional unit of the kidney - produces urine 3 steps to Urine production - filtration, reabsorption, secretion (Fig. 26.8) a. Filtration - movement of material across the filtration membrane into Boman’s capsule as a result of pressure. b. reabsorption of solutes across nephron wall back into the bloo d by active transport and co-transport mechanisms. c. reabsorption of water back into the blood by osmosis d. secretion of solut es across the wall of the nephron into filtrate. Urine produced consists of the substances filltered and secreted into the nephron minus the substances reabsorbed.

A. Filtration -movement of fluid across the filtration membrane (Table 26.2) 1. Renal fraction - part of the total cardiac output that passes through the urine a. 21% of cardiac output flows through the kidney (1) 5600 ml / min X 21% = 1176 ml / min 2. renal blood flow rate = 1176 ml / min 3. Renal plasma flow rate = renal blood flow rate X portion of the blood that is plasma (55%) a. 1176 ml / min X 0.55 = 646 ml / min. 4. Filtration fraction - part of plasma filtered into Bo man’s capsule a. 19% of plasma b. 650 ml / min X 0.19% = 123.5 ml plasma / min c. ~125 ml of filtrate is produced each minute d. Glomerular filtration rate - amount of filtrate produced each minute 3

(1) approximately 180 L per day e. 99% is reabsobed - less than 1 % becomes urine 5. Filtration Barrier a. Filtration membrane: (1) Consists of: the capillary endothelium, basement membrane, podocytes (2) sto ps blood cells and proteins fro m entering Boman’s capsule (a) moleucules larger than 7 nm (40,000 daltons) i) albumin - ~7nm enters in small amounts (3) lets other blood components enter (a) water and solutes of small diameter (b) Small proteins that pass are reabsorbed by endocytosis in proximal tubule. 6. Filtration Pressure a. Result of the sum of the forces that move fluid out of the glomerular capillary into the lumen of bowman’s capsule and those that move the fluid out of the capsule and into the capillary. b. Forces fluid from capillary into the capsule. (1) Glomerular capillary pressure = 45 mmHg (much higher than in most capillaries) (2) Capsule pressure = 10 mmHg (3) Colloid osmotic pressure - result of unfiltered plasma proteins remaining in capillary (a) = 28 mmHg. (4) Total filtration pressure is ~ 10 mmHg. (a) 45 - 10 -28 = 7 mmHg c. Pressure is determined by the diameter size of afferent and efferent capillaries (1) afferents and glomerular capillaries have a large diameter and low resistance. (2) efferents have a small diameter and high resistance. (a) As vessel diameter decreases, resistance to flow increases resulting in a higher pressure in the glomerular capillary. (3) Diameters are adjustable by the smooth muscle in walls of afferent and efferent arterioles. B. Tubular reabsorption - movement of substances from the filtrate back into the blood 1. Filtrate leaves capsule and travels through the ducts a. Substances in filtrate must be reabsorbed. b. Solutes to be reabsorbed: (1) amino acids, glucose, fructose, Na+ , K+, Ca++, HCO 3-, Cl(a) transported acro ss the epithelial cells of nephron by cotransport (2) Water follows solutes (a) Water is reabsorbed as solutes move back into low pressure peritubular capillaries c. Urine is composed of high concentrations of: (1) Urea, uric acid, creatinine, K+ (2) can be toxic in high concentrations d. Regulation of the conc entration of the urine is re gulated by the p ermea bility

and rea bsorption c haracte ristics of the diffe rent portions of the nephr on. (1) 99% of the volume of the filtrate is reabsorbed 2. Transport in the proximal tubule -(remind of structure) 4

a. Active transport of Na+ (Basal membrane) (1) from cytoplasm through the basal cell membrane to interstitial fluid (outside duct) (2) creates a low concentration of Na+ in the cell (3) result: net movement of Na+ from high concentration in duct into the cells of the duct. (4) This concentration gradient is the source of energy for other transport mechanisms. b. Cotransport (1) Carrier molecules on the Apical membrane: (a) move amino acids, glucose, phosphate, lactate, chloride ions. (b) are specific (2) concentration gradient for Na+ ions provides the energy. (3) Cotransported molecules move through the basal membrane by fascilitated diffusion c. Countertransport is used for H+ ions (1) As Na+ ions move into the cell, H+ ions are move out of the cell. d. Diffusion between cells. (1) K+, Ca++, Mg++ move from lumen, between cells into interstitial space by diffusion. e. Water follows Solutes (1) Amino acids, Na++, K+, HCO3-, and Cl- are moved against their concentration gradient (2) Water follows the movement of ions by osmosis f. 65% of filtrate is reabsorbed in proximal tubule. (1) Concentration of filtrate remains about the same as the interstitial fluid 3. Transport in the Loop of Henle a. Descending limb (1) concentration of solutes is high in medulla (2) permiability is high to water and moderat e to urea, Na+ and other ions (3) water moves out or nephron, some solutes move in (4) filtrate volume is reduced by another 15% (5) filtrate is concentrated (1200 mOsm / L) compared to 300 mOsm / L in blood b. Ascending limb (1) impermeable to water (2) Na+, K+ and Cl- ions are trasported out of nephron into the interstitial fluid. (3) result: (a) the concentration of the solutes is reduced to 100mOsm when it reaches the distal tubule (b) filtrate is much more dilute(lower concentration of solutes) than when it enters the loop of Henle. 4. Transport in the Distal Tubule and Collecting Duct a. Na+ and Cl- ions are active transported across the wall b. Osmolarity changes from cortex (300 mOsm) to medulla (1200 mOSm) c. Permeability is dependent on the pressence of ADH (1) ADH increases permeability of cell to water (a) water moves by osmosis out of tubule and duct (2) No ADH: Cells are impermiable to water (a) water remains in the nephron (3) Fitrat e movemement summary: 5

(a) 65% of filtrate removed in proximal tubule (b) 15% in loop of Henle (c) 19% in distal tubule and collecting duct when ADH is present 5. Changes in the Concentration of Solutes in the Nephron a. Urea - enters the nephron at the same concentration as the blood (1) it is only passively reabsorbed (a) 40-60% taken back up while 99% of water is reabsorbed (b) Result: i) concentration of urea increases as water is removed. ii) Urea is excret ed from the body b. Urate ions, creatinine sulfates, phosphates and nitrat es are removed in a similar way. (1) removal of toxic substances maintains homeo stasis C. Tubular Secretion - active transport of substances into the nephron. 1. Can be active or passive 2. Ammonia is synthesized in the epithelial cells of ducts and passively diffuses into the nephron 3. H+, K+ ions are actively transported into the nephron (Proximal and distal tubules) 4. Penicillin - not normally found in the body is actively transported out. D. Urine concentration mechanism 1. Kidney can produce urine of varying concentrations a. From 65 to 1200 mOsm / L b. When large volumes of water are consumed the kidney produces large amounts of dilute urine c. When water is limited the urine is concentrated. d. Homeostatis is maintained at 300 mOsm / L 2. Medullary concentration gradient a. Osmolarity in tips of renal pyramids reaches 1200 mOsm/kg tissue b. Depends on vasa recta, loop of Henle and distribution of urea. (1) Vasa recta (a) reabsorb water and solutes that enter the interstitial fluid (b) must reabsorb water etc while maintaining a high concentration of solutes in the medullary interstitial fluid. (c) forms a countercurrent system (note blood flow is reversed to tubule flow) i) Blood flows from cortex to the medulla and back in parallel tubules to the loop of Henle but in a reversed direction of flow (ie. Counter current). ii) As if blood flows to the medulla a) water diffuses from the blood into the interstitial space b) solutes flow from concentrated interstitial fluid into blood iii) At apex a) blood is the same concentration as the interstitial fluid iv) Medulla to cortex a) solutes diffuse out of vasa recta into interstitial fluid b) water diffuses into the blood. v) blood leaving is only slightly more concentrated than blood entering (2) Loop of Henle (a) Countercurrent multiplier system i) increases the concentration of Na+ ions within the medulla while making the filtrate dilute. 6

ii) the countercurrent system is assisted by active transport mechanisms a) moves solutes from the lumen of ascending limb to interstitial fluid b) ascending limb is not permiable to water. c) water is carried away iii) makes the concentrating function of the kidney more efficient iv) Active transport of solutes helps maintian a high concentration of solutes in the interstitial fluid of the medulla v) filtrate in ascending limb decreases from 1200mOsm to 100 mOsm/kg. (3) Urea (a) Urea diffuses into descending limb of loop (b) Ascending limb of the loop of Henle and distal tubules are not permeable to urea (c) collecting duct are permiable (d) urea diffuses o ut of collecting duct and into the descending limb (e) Result: A high concentration of Urea is maintained in the medulla 3. Summary of Changes in Filtrate Volume and Concentration a. 180 L of filtrate enters the nephron each day b. 65% reabsorbed in the proximal tubule (1) solutes are transported from the lumen into the interstitial fluid (2) water follows - proximal tubule is permeable to water c. 15% of filtrate is reabsorbed in the descending loop of Henle (1) Loop passes through the concentrated fluid of the medulla (2) Descending limb is permeable to water (3) Water diffuses out of the tubule into the concentrated interstitial fluid. (4) Concentration inside = concentration outside by apex of medulla. d. Ascending Limb is not permeable to water (1) Na+, K+ and Cl- are actively transported out of the filtrate and into the interstitial fluid (2) Result: No change in volume but concentration drops to 100mOsm/L (less concentrated than cortex) e. Distal tubule and collecting duct are permeable to water if ADH is present. (1) With ADH - water diffuses from the concentrated filtrate into the interstitial fluid. (2) 19% of filtrate is reabsorbed. f. 1% of filtrate remains as urine. III.

Regulation of Urine Concentration and Vo lume A. Urine can be dilute or very concentrated and can be produced in small or large amounts 1. Filtrate reabsorption in the proximal tubule and descending limb is obligatory 2. Reabsorption in the distal tubule and collecting duct is regulated a. Homeostasis is maintained by these segments b. Regulation involves hormonal mechanisms, autoregulation and the nervous system. B. Hormonal Mechanisms 1. Antidiuretic Hormone a. Released from posterior pitutitary (1) made in supraoptic nucleus which has osmoreceptors. (2) regulated by blood pressure (baroreceptors) in aorta that send signals to supraoptic b. Blood volume decrease, BP decreases and/or osmolarity increases (1) result: 7

(a) greater release of ADH and (b) greater reabsorption of water from distal tubule and collecting duct c. Volume increases and osmolarity decreases (1) result: (a) decrease in ADH release (b) decrease in reabsorption of water from distal tubule and collecting duct d. Diabetes insipidus - large volume, no taste (1) due to insufficient ADH production (2) 10 - 20 L of urine produced / day e. Diabetes mellitus- large volume w/ glucose 2. Renin-Angiot ensin-Aldosterone a. Renin (1) produced by the juxtaglomerular apparatus (2) Rate of production increases as BP decreases or Na+ (Cl-)concentration decreases (3) monitored by the macula densa b. Renin causes angiotensinogen to be converted to angiotensin I c. Angiotensin I is converted to angiotensin II in the lungs. d. Angiotensin II (1) is a potent vasoconstrictor and (2) activates the zona glomerulosa of adrenal to produce aldosterone. e. Aldosterone (1) increase the expression/ synthesis of transport proteins for Na+ ions across the membrane (2) Result: increased reabsorption (active transport) of Na+ in ascending limb of Loop and excretion of K+ and H+ 3. Atrial Nat uiuretic Hormone a. Secreted by cardiac muscle b. BP increase causes increase in production c. ANH inhibits ADH secretion d. Decrease in ADH causes large amounts of dilute urine to be produced. e. Blood volume and pressure drops. C. Autoregulation 1. Involves changes in the degree of constriction in the afferent arterioles - thus changing the rate of filtation. 2. Mechanism unclear 3. BP increase results in constriction of afferent arterioes a. Prevents an increase in renal blood flow and filtration pressure / filtrate formation 4. BP decreases - dilation of the afferent arteriole a. Prevents a decrease in renal blood flow and filtration pressure D. Effect fo Sympathetic Stimulation of Kidney Function 1. Sympathetic neurons: a. innervate blood vessels releasing NE and b. constricting small arteries and afferent arteioles 8

2. Decreases renal blood flow and filtrate formation. 3. Shock or intense exercise decreases the rate of urine formation. 4. Extreme shock can reduce blood flow to the kidney to the degree that normal metabolism is affected - results in kidney tissue damage . IV.

Urine Movement A. Urine Flow Through the Nephron and the Ureters 1. Flow into the renal pelvis is due to hydrostatic pressure generated at the glomerulus 2. Urine flows through ureters due to peristaltic movement in the ureters. a. Peristaltic movement can generate pressure of 50 mmHg. b. Pressure in the bladder compresses the uret er at the trigone prevent ing backflow o f urine c. Bladder pressure increases as bladder is filled d. Capacity 400-500 ml no change in pressure e. Above 500 ml pressure increases causing a micturition reflex B. Micturition Reflex

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