Urinary System I: Kidneys and Urine Formation

1. Urinary System I: Kidneys and Urine Formation • Functions of the Urinary System • Organs of the Urinary System • The Kidney • Coverings and Regions • Blood Flow • Nephrons: Glomeruli and Renal Tubules • Urine Formation • Urinalysis • Ureters, Bladder, and Urethra

2. Functions of the Urinary System: Blood Filtration • Elimination of waste products • Nitrogenous wastes (amino groups from amino acids) • Toxins • Drugs • Regulate aspects of homeostasis • Water balance • Electrolytes • Acid-base balance in the blood • Blood pressure • Red blood cell production (erythropoietin) • Activation of vitamin D

3. Organs of the Urinary system • Kidneys • Against the dorsal body wall • At the level of T12 to L3 • The right kidney is slightly lower than the left • Retroperitoneal (posterior to and outside of parietal peritoneum) • Attached to ureters, renal blood vessels, and nerves at renal hilus • Covered with adipose • Ureters • Urinary bladder • Urethra

4. Coverings of the Kidneys • Renal capsule • Surrounds each kidney • Adipose capsule • Fascia layer/adventitia (connective tissue) substitutes for serosae outside of peritoneal cavity • Surrounds the kidney • Provides protection to the kidney • Helps keep the kidney in its correct location

5. Regions of the Kidney • Kidney Regions • Renal cortex – outer region • Renal medulla – inside the cortex • Renal pelvis – inner collecting tube • Kidney Structures • Medullary pyramids – triangular regions of tissue in the medulla • Renal columns – extensions of cortex-like material inward • Calyces – cup-shaped structures that funnel urine towards the renal pelvis

6. Blood Flow in the Kidneys Glomerular capillaries Peritubular capillaries Unique: Incoming vessels enter as an arteriole, narrow into a capillary bedin the glomerulus, leave in an arteriole, and then break into the peritubular capillary bed before leaving as venus blood.

7. The Nephron

8. Glomerulus and Bowman’s Capsule • A specialized capillary bed • Attached to narrow arterioles on both sides (maintains high pressure in capsule) • Fenestrated glomerular endothelium • Allows filtrate to pass from plasma into the glomerular capsule • Layers of Bowman’s capsule • Parietal layer: simple squamous epithelium • Visceral layer: branching epithelial podocytes • Extensions terminate in foot processes that cling to basement membrane • Filtration slits allow filtrate to pass into the capsular space Filtration slits Capsular space

9. Renal Tubule • Proximal convoluted tubule • Loop of Henle • Distal convoluted tubule • Collecting duct Figure 15.3b

10. Two Types of Nephrons • Cortical nephrons • Located entirely in the cortex • Includes most nephrons (> 85%) • Juxtamedullary nephrons • Found at the boundary of the cortex and medulla • Important in the production of concentrated urine Cortex Medulla

11. Juxtaglomerular Apparatus (JGA) • Macula densa: sensors of the filtrate • Tall, closely packed cells lining the ascending Lof H or PCT • Water and NaCl concentration detected by osmo -and chemoreceptors • If ↓filtrate water volume, then stimulation of renin release by JG, ↑blood water volume , ↑blood pressure . • If ↓NaCl in PCT filtrate; ↑dilation of afferent arteriole  ↓reduce filtration rate, ↑Na + stays in filtrate by tubules, ↑blood Na+ , • If ↑NaCl in PCT filtrate; then ↑renin release by JG, ↑blood water volume , ↑blood pressure . • Granular cells (juxtaglomerular, or JG cells): pressure sensors of incoming blood and storage of renin • Enlarged, smooth muscle cells of blood afferent arteriole • Secretory granules release renin when epi & NE in blood • Act as mechanoreceptors that sense low blood pressure • Responds to stimuli by macula densa • Extraglomerular mesangial cells

12. Peritubular Capillaries • Arise from efferent arteriole of the glomerulus • Cling to adjacent renal tubules in cortex • Low-pressure, porous capillaries adapted for absorption • Reabsorb (reclaim) some substances from collecting tubes • Empty into venules • Vasa recta are the long vessels parallel to long loops of Henle Filtrate efferent afferent arterioles Water is reclaimed from filtrate into venous circulation via peritubular capillaries

13. Epithelia in the Tubules Are Designed for Filtration and Absorption Glomerular capsule: parietal layer Renal cortex Basement membrane Renal medulla Renal corpuscle Podocyte • Glomerular capsule Renal pelvis Fenestrated endothelium of the glomerulus • Glomerulus Distal convoluted tubule Ureter Glomerular capsule: visceral layer Kidney Microvilli Mitochondria Proximal convoluted tubule Highly infolded plasma membrane Cortex Proximal convoluted tubule cells and thick ascending L 0f H Medulla Thick segment Distal convoluted tubule cells Thin segment Loop of Henle • Descending limb • Ascending limb Collecting duct Loop of Henle (thin-segment) cells Principal cell Intercalated cell Mostly cuboidal epithelium with modifications in membrane surfaces Collecting duct cells Figure 25.5

14. Urine Formation Processes • A. Filtration • Nonselective passive process • Water and solutes smaller than proteins are forced through capillary walls, no cells - essentially plasma • Filtrate is collected in the glomerular capsule and leaves via the renal tubule • Blood pressure relatively high in glomerulus • Efficient filtration driven by hydrostatic pressure • B. Tubular Reabsorption • The peritubular capillaries reabsorb several materials: H2O, glucose, amino acids, ions • Some reabsorption is passive, most is active • Nitrogenous waste products not reabsorbed, nor excess water, urea, uric acid, or creatinine • Most reabsorption occurs in the proximal convoluted tubule • C. Tubular Secretion • Some materials pumped from the peritubular capillaries into the renal tubules: H+, K+, creatinine • Materials left in the renal tubule move toward the ureter

15. Net Filtration Pressure (NFP) at the Glomerulus Afferent arteriole Glomerular capsule NFP = HPg – (OPg + HPc) = (push outwards - back pressure inwards) Glomerular (blood) hydrostatic pressure (HPg = 55 mm Hg) 10 mm Hg Blood colloid osmotic pressure (Opg = 30 mm Hg) Net filtration pressure Capsular hydrostatic pressure (HPc = 15 mm Hg) Figure 25.11

16. Glomerular Filtration Rate • Volume of filtrate formed per minute by the kidneys (120–125 ml/min) • Governed by (and directly proportional to) • Total surface area available for filtration • Filtration membrane permeability • Flow rate (GFR) is tightly controlled by two types of mechanisms • Intrinsic controls (renal autoregulation) • Extrinsic controls (nervous and endocrine regulation

17. Intrinsic Controls (Renal Autoregulation) of GFR • Local action within the kidney • Myogenic mechanism •  BP  constriction of afferent arterioles • Helps maintain normal GFR • Protects glomeruli from damaging high BP •  BP  dilation of afferent arterioles • Helps maintain normal GFR • Tubuloglomerular feedback mechanism, which senses changes in the juxtaglomerular apparatus • Flow-dependent mechanism directed by the macula densa cells • If GFR increases, filtrate flow rate increases in the tubule • Filtrate NaCl concentration will be high because of insufficient time for reabsorption • Macula densa cells of the JGA respond to NaCl by releasing a vasoconstricting chemical that acts on the afferent arteriole  GFR

18. Extrinsic controls of GFR • Nervous and endocrine mechanisms that maintain blood pressure, but affect kidney function • Under normal conditions at rest • Renal blood vessels are dilated • Renal autoregulation mechanisms prevail • Under extreme stress • Norepinephrine is released by the sympathetic nervous system; epinephrine is released by the adrenal medulla • NE and Epi cause constriction of afferent arterioles, inhibiting filtration and triggering the release of renin from JGA cells leading to renin-angiotensin cascade

19. Extrinsic Controls: Renin-Angiotensin Mechanism • Triggered when the granular cells of the JGA release renin angiotensinogen (a plasma globulin) renin angiotensin I angiotensin converting enzyme (ACE) angiotensin II

20. Effects of Angiotensin II • Constricts arteriolar smooth muscle, causing mean arterial pressure to rise (hypertensive) • Stimulates the reabsorption of Na+ • Acts directly on the renal tubules • Triggers adrenal cortex to release aldosterone (hypertensive • Stimulates the hypothalamus to release ADH and activates the thirst center (increases hydration) • Constricts efferent arterioles, decreasing peritubular capillary hydrostatic pressure and increasing fluid reabsorption (saves water) • Causes glomerular mesangial cells to contract, decreasing the surface area available for filtration (saving water)

21. Extrinsic Controls: Renin-Angiotensin Mechanism • Triggers for renin release by granular cells • Reduced stretch of granular cells (MAP below 80 mm Hg) • Stimulation of the granular cells by activated macula densa cells • Direct stimulation of granular cells via 1-adrenergic receptors by renal nerves

22. SYSTEMIC BLOOD PRESSURE (–) Blood pressure in afferent arterioles; GFR Baroreceptors in blood vessels of systemic circulation Granular cells of juxtaglomerular apparatus of kidney GFR Release (+) Stretch of smooth muscle in walls of afferent arterioles Filtrate flow and NaCl in ascending limb of Henle’s loop (+) (+) Renin Sympathetic nervous system Catalyzes cascade resulting in conversion Targets Vasodilation of afferent arterioles Angiotensinogen Angiotensin II (+) (+) (+) Macula densa cells of JG apparatus of kidney Adrenal cortex Systemic arterioles Releases Vasoconstriction; peripheral resistance Aldosterone Release of vasoactive chemical inhibited Targets Kidney tubules Vasodilation of afferent arterioles Na+ reabsorption; water follows (+) Stimulates (–) Inhibits Increase Decrease GFR Blood volume Systemic blood pressure Tubuloglomerular mechanism of autoregulation Myogenic mechanism of autoregulation Hormonal (renin-angiotensin) mechanism Neural controls Intrinsic mechanisms directly regulate GFR despite moderate changes in blood pressure (between 80 and 180 mm Hg mean arterial pressure). Extrinsic mechanisms indirectly regulate GFR by maintaining systemic blood pressure, which drives filtration in the kidneys. Figure 25.12

23. Urine Formation Processes • A. Filtration • Nonselective passive process • Water and solutes smaller than proteins are forced through capillary walls, no cells - essentially plasma • Filtrate is collected in the glomerular capsule and leaves via the renal tubule • Blood pressure relatively high in glomerulus • Efficient filtration driven by hydrostatic pressure • B. Tubular Reabsorption • The peritubular capillaries reabsorb several materials: H2O, glucose, amino acids, ions • Some reabsorption is passive, most is active • Nitrogenous waste products not reabsorbed, nor excess water, urea, uric acid, or creatinine • Most reabsorption occurs in the proximal convoluted tubule • C. Tubular Secretion • Some materials pumped from the peritubular capillaries into the renal tubules: H+, K+, creatinine • Materials left in the renal tubule move toward the ureter

24. Mechanism of Urine Formation Hormone regulated reabsorption of Ca2+ ( by PTH), water ( ADH) Na+ ( aldosterone and ANP) Most reabsorption occurs here • In general: •  ADH • Concentrated urine • Water conservation ---------------- •  Aldosterone (often triggered by  Angio-tensin II) • Dilute urine • Na+ conservation • Blood pressure H2O  Urea reabs. with  ADH Reduces the volume and saltiness of the filtrate Na+, K+ resabsorbed

25. Countercurrent Mechanism • Occurs when fluid flows in opposite directions in two adjacent segments of the same tube • E.g. Filtrate flow in the loop of Henle (countercurrent multiplier) • E.g. Blood flow in the vasa recta (countercurrent exchanger) • Role of countercurrent mechanisms • Establish and maintain an osmotic gradient • Allow the kidneys to vary urine concentration (but especially make dilute urine) • Allow for more efficient exchange of ions or gases

26. Countercurrent Multiplier: Loop of Henle • Descending limb • Freely permeable to H2O, which passes out of the filtrate into the hyperosmotic medullary interstitial fluid • Filtrate osmolality increases to ~1200 mOsm • Ascending limb • Impermeable to H2O • Selectively permeable to solutes • Na+ and Cl– are passively reabsorbed in the thin segment, actively reabsorbed in the thick segment • Filtrate osmolarity decreases to 100 mOsm

27. Countercurrent in Loop of Henle Extracts Water thenSalt Osmolality of interstitial fluid (mOsm) H2O NaCI Cortex Active transport Passive transport NaCI H2O Water impermeable NaCI H2O The salty outer medulla created by the ascending loop amplifies the extraction of water in the descending loop. Without countercurrent, much less water would be removed and therefore would be less efficient. NaCI H2O Outer medulla H2O NaCI H2O H2O Inner medulla Loop of Henle Renal function online animation Figure 25.16a (a) Countercurrent multiplier. The long loops of Henle of the juxtamedullary nephrons create the medullary osmotic gradient.

28. Countercurrent Exchanger: Vasa Recta • The Vasa Recta (peritubular capillaries parallel to the Loop of Henle • Maintain the osmotic gradient • Deliver blood to the medullary tissues • Protect the medullary osmotic gradient by preventing rapid removal of salt, and by removing reabsorbed H2O

29. Countercurrent in Loop of Henle Peritubular Capillaries Maintains Salt Gradient Osmolality of interstitial fluid (mOsm) Blood from efferent arteriole Passive transport To vein NaCI H2O NaCI H2O Cortex The saltier cortex created by the ascending vasa recta peritubular capillaries amplifies the extraction of water in the descending loop. Without countercurrent, much less would remain in the blood. NaCI H2O NaCI H2O Online kidney physiology animation Outer medulla NaCI H2O NaCI H2O NaCI H2O NaCI H2O Inner medulla Vasa recta (b) Countercurrent exchanger. The vasa recta preserves the medullary gradient while removing reabsorbed water and solutes. Figure 25.16b

30. Urea Recycling • Urea moves between the collecting ducts and the loop of Henle • Secreted into filtrate by facilitated diffusion in the ascending thin segment • Reabsorbed by facilitated diffusion in the collecting ducts deep in the medulla • More collecting duct reabsorption if ADH present • Contributes to the high osmolality in the medulla

31. Diuretics • Chemicals that enhance the urinary output • Osmotic diuretics: substances not reabsorbed, (e.g., high glucose in a diabetic patient) causes increased water and urine volume • ADH inhibitors such as alcohol • Substances that inhibit Na+ reabsorption and obligatory H2O reabsorption such as caffeine and many drugs

32. Kidney Dialysis Continuous ambulatory peritoneal dialysis (CAPD)