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 T 12 to L 3 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 Unique: Incoming vessels enter as an arteriole, narrow into a capillary bed in the glomerulus, leave in an arteriole, and then break into the peritubular capillary bed before leaving as venus blood. Peritubular capillaries Glomerular capillaries

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 oExtensions terminate in foot processes that cling to basement membrane oFiltration slits allow filtrate to pass into the capsular space Capsular space Filtration slits

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 Medulla Cortex

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 efferent afferent arterioles Water is reclaimed from filtrate into venous circulation via peritubular capillaries Filtrate

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

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: H 2 O, 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. Figure 25.11 Glomerular capsule Afferent arteriole 10 mm Hg Net filtration pressure Glomerular (blood) hydrostatic pressure (HP g = 55 mm Hg) Blood colloid osmotic pressure (Op g = 30 mm Hg) Capsular hydrostatic pressure (HP c = 15 mm Hg) NFP = HP g – (OP g + HP c ) = (push outwards - back pressure inwards) Net Filtration Pressure (NFP) at the Glomerulus

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 oIntrinsic controls (renal autoregulation) oExtrinsic controls (nervous and endocrine regulation

17. Intrinsic Controls (Renal Autoregulation) of GFR  Local action within the kidney Myogenic mechanism o  BP  constriction of afferent arterioles  Helps maintain normal GFR  Protects glomeruli from damaging high BP o  BP  dilation of afferent arterioles  Helps maintain normal GFR Tubuloglomerular feedback mechanism, which senses changes in the juxtaglomerular apparatus oFlow-dependent mechanism directed by the macula densa cells oIf GFR increases, filtrate flow rate increases in the tubule oFiltrate NaCl concentration will be high because of insufficient time for reabsorption oMacula 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 1.Constricts arteriolar smooth muscle, causing mean arterial pressure to rise (hypertensive) 2.Stimulates the reabsorption of Na + Acts directly on the renal tubules Triggers adrenal cortex to release aldosterone (hypertensive 3.Stimulates the hypothalamus to release ADH and activates the thirst center (increases hydration) 4.Constricts efferent arterioles, decreasing peritubular capillary hydrostatic pressure and increasing fluid reabsorption (saves water) 5.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. Figure 25.12 Stretch of smooth muscle in walls of afferent arterioles Blood pressure in afferent arterioles; GFR Vasodilation of afferent arterioles GFR Myogenic mechanism of autoregulation Release of vasoactive chemical inhibited 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. Tubuloglomerular mechanism of autoregulation Hormonal (renin-angiotensin) mechanism Neural controls SYSTEMIC BLOOD PRESSURE GFR Macula densa cells of JG apparatus of kidney Filtrate flow and NaCl in ascending limb of Henle’s loop Targets Granular cells of juxtaglomerular apparatus of kidney AngiotensinogenAngiotensin II Adrenal cortexSystemic arterioles (+) Renin Release Catalyzes cascade resulting in conversion (+) Kidney tubules Aldosterone Releases Targets Vasoconstriction; peripheral resistance Blood volume Na + reabsorption; water follows Systemic blood pressure (+) (–) Increase Decrease Stimulates Inhibits Baroreceptors in blood vessels of systemic circulation Sympathetic nervous system (+) (–) Vasodilation of afferent arterioles

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: H 2 O, 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 Most reabsorption occurs here Na +, K + resabsorbed Hormone regulated reabsorption of Ca 2+ (  by PTH), water (  ADH) Na + (  aldosterone and ANP) H2OH2O  Urea reabs. with  ADH In general:  ADH  Concentrated urine  Water conservation ----------------  Aldosterone (often triggered by  Angio- tensin II)  Dilute urine  Na + conservation  Blood pressure Reduces the volume and saltiness of the filtrate

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 H 2 O, which passes out of the filtrate into the hyperosmotic medullary interstitial fluid Filtrate osmolality increases to ~1200 mOsm  Ascending limb Impermeable to H 2 O Selectively permeable to solutes oNa + and Cl – are passively reabsorbed in the thin segment, actively reabsorbed in the thick segment Filtrate osmolarity decreases to 100 mOsm

27. Loop of Henle Osmolality of interstitial fluid (mOsm) Inner medulla Outer medulla Cortex Active transport Passive transport Water impermeable (a) Countercurrent multiplier. The long loops of Henle of the juxtamedullary nephrons create the medullary osmotic gradient. H2OH2O H2OH2O H2OH2O H2OH2O H2OH2O H2OH2O H2OH2O NaCI Countercurrent in Loop of Henle Extracts Water then Salt Figure 25.16a Renal function online animation 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.

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 H 2 O

29. NaCI H 2 O NaCI H 2 O NaCI H 2 O NaCI H 2 O NaCI H 2 O NaCI H 2 O NaCI H 2 O NaCI H 2 O Vasa recta To vein Osmolality of interstitial fluid (mOsm) Blood from efferent arteriole Inner medulla Outer medulla Cortex Passive transport (b) Countercurrent exchanger. The vasa recta preserves the medullary gradient while removing reabsorbed water and solutes. Figure 25.16b Countercurrent in Loop of Henle Peritubular Capillaries Maintains Salt Gradient Online kidney physiology animation 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.

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 H 2 O reabsorption such as caffeine and many drugs

32. Kidney Dialysis Continuous ambulatory peritoneal dialysis (CAPD)