1. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chapter 17 Physiology of the Kidneys 17-1

2. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Kidney Function  Regulation of ECF through formation of urine. (primary function).  Regulate volume of blood plasma.  BP.  Regulate concentration of waste products in the blood.  Regulate concentration of electrolytes.  Na +, K +, and HC0 3 -.  Regulate pH. 17-3

3. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Structure of Urinary System  Paired kidneys are on either side of vertebral column below diaphragm  About size of fist  Urine flows from kidneys into ureters which empty into bladder 17-5

4. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Structure of Kidney  Cortex contains many capillaries & outer parts of nephrons  Medulla consists of renal pyramids separated by renal columns  Pyramid contains minor calyces which unite to form a major calyx Fig 17.2 17-6

5. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Structure of Kidney continued  Major calyces join to form renal pelvis which collects urine  Conducts urine to ureters which empty into bladder Fig 17.3 17-7

6. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Nephron  Is functional unit of kidney responsible for forming urine  >1 million nephrons/kidney  Is a long tube & has associated blood vessels Fig 17.2 17-10

7. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Renal Blood Vessels  Blood enters kidney through renal artery  Which divides into interlobar arteries  That divide into arcuate arteries that give rise to interlobular arteries 17-11

8. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Renal Blood Vessels  Interlobular arteries give rise to afferent arterioles which supply glomeruli  Glomeruli are masses of capillaries inside glomerular capsule that gives rise to filtrate that enters nephron tubule  Efferent arteriole drains glomerulus & delivers that blood to peritubular capillaries (vasa recta)  Blood from peritubular capillaries enters veins 17-12

9. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Vasa Recta  Extend from deeper portions of peritubular capillary network which surround juxtamedullary nephrons.  So are deep into medulla and important in maintaining salt concentration in medulla.  Only 1%-2% of blood entering kidney goes to vasa recta vessels.

10. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 17-13

11. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Nephron Tubules  Tubular part of nephron begins with glomerular capsule which transitions into proximal convoluted tubule (PCT), then to descending & ascending limbs of Loop of Henle (LH), & distal convoluted tubule (DCT)  Tubule ends where it empties into collecting duct (CD) 17-14

12. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glomerular (Bowman's) Capsule  Surrounds glomerulus  Together they form renal corpuscle  Is where glomerular filtration occurs  Filtrate passes into PCT Glomerular capsule PCT 17-15

13. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Proximal Convoluted Tubule  Walls consist of single layer of cuboidal cells with millions of microvilli. Function?  They increase surface area for reabsorption 17-16

14. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Type of Nephrons  Cortical nephrons originate in outer 2/3 of cortex  Juxtamedullary nephrons originate in inner 1/3 cortex  Have long LHs  Important in producing concentrated urine 17-17

15. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Vasa Recta  Blood vessels that extend from deeper portions of peritubular capillary network which surround juxtamedullary nephrons.  So are deep into medulla and important in maintaining salt concentration in medulla.  Only 1%-2% of blood entering kidney goes to vasa recta vessels.

16. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glomerular Filtration  Glomerular capillaries & Bowman's capsule form a filter for blood  Glomerular Caps are fenestrated--have large pores between their endothelial cells  100-400 times more permeable than other Caps  Small enough to keep RBCs, platelets, & WBCs from passing  Pores are lined with negative charges to keep blood proteins from filtering 17-19

17. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  To enter tubule filtrate must pass through narrow filtration slits formed between pedicels of podycytes of glomerular capsule Glomerular Filtration continued 17-20

18. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 17-21

19. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Fig 17.9 17-22

20. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glomerular Ultrafiltrate  Is fluid that enters glomerular capsule, whose filtration was driven by blood pressure 17-23

21. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glomerular Filtration Rate (GFR)  Is volume of filtrate produced by both kidneys/min  Averages 115 ml/min in women; 125 ml/min in men  Totals about 180L/day (45 gallons)  So most filtered water must be reabsorbed or death would ensue from water lost through urination 17-24

22. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Filtration Pressure  Filtration of blood depends on the force of glomerular blood hydrostatic pressure in relation to two opposing forces:  capsular hydrostatic pressure  blood colloidal osmotic pressure.

23. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Filtration Pressure  Osmotic pressure = 30 mm Hg.  Capsular hydrostatic pressure = 20 mm Hg.  So hydrostatic pressure of glomerular blood must be greater than 50 mm Hg or filtration ends. Usually = 60 mm Hg.

24. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. GF Facilitated by:  Length of highly coiled glomerular capillaries providing vast surface area.  Filtration membrane structure; endothelial pores, basement membrane (semi- permeable), filtration slits.  Efferent arteriole smaller than afferent so pressure higher than in other capillaries.  Avg. = 60mm Hg as compared to 30mm Hg in others  Endothelial membrane of capillaries thinner than other capillaries

25. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Regulation of GFR  Is controlled by extrinsic & intrinsic (autoregulation) mechanisms  Vasoconstriction or dilation of afferent arterioles affects rate of blood flow to glomeruli & thus GFR 17-25

26. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Sympathetic Effects  Sympathetic activity constricts afferent arteriole  Helps maintain BP & shunts blood to heart & muscles 17-26

27. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Renal Autoregulation  Allows kidney to maintain a constant GFR over wide range of BPs  Achieved via effects of locally produced chemicals on afferent arterioles  When average BP drops to 70 mm Hg afferent arteriole dilates  When average BP increases, afferent arterioles constrict 17-27

28. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 17-28

29. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Renal Autoregulation  Is also maintained by negative feedback between afferent arteriole & volume of filtrate (tubuloglomerular feedback)  Increased flow of filtrate sensed by macula densa (part of juxtaglomerular apparatus) in thick ascending LH  Signals afferent arterioles to constrict 17-29

30. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Juxtaglomerular Apparatus  Region in each nephron where the afferent arterioles come in contact with the thick ascending limb of the loop.  Smooth muscle cells become modified into granular cells which secrete renin.  Macula densa: Inhibit renin secretion when blood [Na + ] increases.

31. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Renin-angiotension Pathway  Low Na causes juxta-glomerular cells to release renin.  R-A pathway causes vasoconstriction of efferent arterioles  Glomerular pressure rises  Aldosterone produced and increases Na

32. Function of Nephron Segments 17-30

33. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Reabsorption of Salt & H 2 0  In PCT returns most molecules & H 2 0 from filtrate back to peritubular capillaries  About 180 L/day of ultrafiltrate produced; only 1–2 L of urine excreted/24 hours  Urine volume varies according to needs of body  Minimum of 400 ml/day urine necessary to excrete metabolic wastes (obligatory water loss) 17-31

34. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Reabsorption of Salt & H 2 0 continued  Return of filtered molecules is called reabsorption  Water is never transported  Other molecules are transported & water follows by osmosis Fig 17.13 17-32

35. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. PCT  Filtrate in PCT is isosmotic to blood (300 mOsm/L)  Thus reabsorption of H 2 0 by osmosis cannot occur without active transport (AT)  Is achieved by AT of Na+ out of filtrate  Loss of + charges causes Cl- to passively follow Na+  Water follows salt by osmosis Fig 17.14 17-33

36. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Insert fig. 17.14 Fig 17.15 17-34

37. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Significance of PCT Reabsorption  ≈65% Na +, Cl -, & H 2 0 is reabsorbed in PCT & returned to bloodstream  An additional 20% is reabsorbed in descending loop of Henle  Thus 85% of filtered H 2 0 & salt are reabsorbed early in tubule  This is constant & independent of hydration levels  Energy cost is 6% of calories consumed at rest  The remaining 15% is reabsorbed variably, depending on level of hydration 17-35

38. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Concentration Gradient in Kidney  In order for H 2 0 to be reabsorbed, interstitial fluid must be hypertonic  Osmolality of medulla interstitial fluid (1200-1400 m O sm) is 4X that of cortex & plasma (300 m O sm)  This concentration gradient results largely from loop of Henle which allows interaction between descending & ascending limbs 17-36

39. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Descending Limb LH  Is permeable to H 2 0  Is impermeable to, & does not AT, salt  Because deep regions of medulla are 1400 m O sm, H 2 0 diffuses out of filtrate until it equilibrates with interstitial fluid  This H 2 0 is reabsorbed by capillaries Fig 17.17 17-37

40. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Descending Limb LH  Deeper regions of medulla reach 1400 mOsm/L.  Impermeable to passive diffusion of NaCl.  Permeable to H 2 0.  Hypertonic interstitial fluid causes H 2 0 movement out of the descending limb via osmosis.  Fluid volume decreases in tubule, causing higher [Na+] in the ascending limb.

41. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Ascending Limb LH  Has a thin segment in depths of medulla & thick part toward cortex  Impermeable to H 2 0; permeable to salt; thick part ATs salt out of filtrate  AT of salt causes filtrate to become dilute (100 m O sm) by end of LH Fig 17.17 17-38

42. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. AT in Ascending Limb LH  NaCl is actively extruded from thick ascending limb into interstitial fluid  Na + diffuses into tubular cell with secondary active transport of K + and Cl -  Occurs at a ratio of 1 Na + & 1 K + to 2 Cl - Insert fig. 17.15 Fig 17.16 17-39

43. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  Na + is AT across basolateral membrane by Na + / K + pump  Cl - passively follows Na + down electrical gradient  K + passively diffuses back into filtrate  Walls are impermeable to H 2 0 so filtrate gets diluted as goes up. AT in Ascending Limb LH continued 17-40

44. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Countercurrent Multiplier System  Countercurrent flow & proximity allow descending & ascending limbs of LH to interact in way that causes osmolality to build in medulla  Salt pumping in thick ascending part raises osmolality around descending limb, causing more H 2 0 to diffuse out of filtrate  This raises osmolality of filtrate in descending limb which causes more concentrated filtrate to be delivered to ascending limb  As this concentrated filtrate is subjected to AT of salts, it causes even higher osmolality around descending limb (positive feedback)  Process repeats until equilibrium is reached when osmolality of medulla is 1400 17-41

45. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Countercurrent Multiplication  Flow in opposite directions in the ascending and descending limbs.  Close proximity of the 2 limbs:  Allows interaction.  Positive feedback.

46. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Vasa Recta  Is important component of countercurrent multiplier  Permeable to salt, H 2 0 (via aquaporins), & urea  Recirculates salt, trapping some in medulla interstitial fluid  Reabsorbs H 2 0 coming out of descending limb  Descending section has urea transporters  Ascending section has fenestrated capillaries Fig 17.18 17-42

47. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  Vasa recta maintains hypertonicity by countercurrent exchange.  NaCl and urea diffuse into descending limb and diffuse back into medullary tissue fluid.  [Solute] is higher in the ascending limb than in the tissue fluid.  Walls are permeable to H 2 0, NaCl and urea  Colloid osmotic pressure > interstitial fluid.

48. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 17-44

49. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Urea  Contributes to total osmolality of interstitial fluid.  Ascending limb LH and terminal CD are permeable to urea.  Urea diffuses out CD and into ascending limb.

50. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Collecting Duct  Medullary area impermeable to high [NaCl] that surrounds it.  The walls of the CD are permeable to H 2 0.  H 2 0 is drawn out of the CD by osmosis.  Rate of osmotic movement is determined by the # of aquaporins in the cell membrane.  Permeable to H 2 0 depends upon the presence of ADH.  ADH binds to its membrane receptors on CD, incorporating water channels into cell membrane.

51. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. ADH  Is secreted by post pituitary in response to dehydration  Stimulates insertion of aquaporins (water channels) into plasma membrane of CD  When ADH is high, H 2 0 is drawn out of CD by high osmolality of interstitial fluid  & reabsorbed by vasa recta Fig 17.21 17-46

52. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Osmolality of Different Regions of the Kidney Fig 17.20 17-47

53. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Secretion  Secretion of substances from the blood (peritubular capillaries) to the urine.  Allows the kidneys to rapidly eliminate certain potential toxins.

54. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glucose and Amino Acid Reabsorption  Filtered glucose and amino acids are normally reabsorbed by the nephrons.  Carrier mediated transport:  Saturation.  Exhibit T m.  Renal transport threshold:  Minimum [plasma] of a substance that results in excretion of that substance in the urine.

55. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Renal Plasma Clearance  Substances in the plasma are removed and excreted in the urine.  If a substance is not reabsorbed or secreted, then the amount excreted = amount filtered.

56. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Electrolyte Balance  Kidneys regulate Na +, K +, H +, Cl -, HC0 3 -, PO 4 -2.  Control of Na + important in regulation of blood volume and pressure.  Control of plasma of K + important in proper function of cardiac and skeletal muscles.  Match ingestion with urinary excretion.

57. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Role of Aldosterone  90% K + reabsorbed in early part of the nephron.  When aldosterone is absent, no K+ is excreted in the urine.  Final [K+] controlled in CD by aldosterone.  High [K+] or low [Na+] stimulates the secretion of aldosterone.  Only means by which K + is secreted.

58. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Na + Reabsorption  In the absence of aldosterone, 80% remaining Na + is reabsorbed.  2% is excreted (30 g/day).  Final [Na+] controlled in CD by aldosterone.

59. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Renal Acid-Base Regulation  Kidneys help regulate blood pH by excreting H + and reabsorbing HC0 3 -.  Most of the H + secretion occurs across the walls of the PCT in exchange for Na +.  Normal urine normally is slightly acidic because the kidneys reabsorb almost all HC0 3 - and excrete H +.  Returns blood pH back to normal range.