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Chapter 17

Chapter 17. Physiology of the Kidneys. 17-1. Chapter 17 Outline Overview of Kidney Structure Nephron Glomerular Filtration Function of Nephron Segments Renal Clearance Hormonal Effects Na + , K + , H + , and HCO 3 - Relationships Clinical Aspects. 17-2. Kidney Function.

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Chapter 17

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  1. Chapter 17 Physiology of the Kidneys 17-1

  2. Chapter 17 Outline • Overview of Kidney Structure • Nephron • Glomerular Filtration • Function of Nephron Segments • Renal Clearance • Hormonal Effects • Na+, K+, H+, and HCO3- Relationships • Clinical Aspects 17-2

  3. Kidney Function • Is to regulate plasma and interstitial fluid by formation of urine • In process of urine formation, kidneys regulate: • Volume of blood plasma, which contributes to BP • Waste products in blood • Concentration of electrolytes • Including Na+, K+, HCO3-, and others • Plasma pH 17-3

  4. Overview of Kidney Structure 17-4

  5. 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

  6. Structure of Kidney • Cortex contains many capillaries and outer parts of nephrons • Medulla consists of renal pyramids separated by renal columns • Pyramid contains minor calyces which unite to form a major calyx 17-6

  7. Structure of Kidney continued • Major calyces join to form renal pelvis which collects urine • Conducts urine to ureters which empty into bladder 17-7

  8. Micturition Reflex (Urination) • Bladder has a smooth muscle wall called the detrussor muscle • Stretch can cause spontaneous APs and contraction • Also innervated and controlled by parasympathetic • Drugs for overactive bladders target muscarinic receptors 17-8

  9. Micturition Reflex (Urination) continued • Actions of internal and externalurethralsphincters are regulated by reflex center located in sacral part of cord • Filling of bladder activates stretch receptors that send impulses to micturition reflex center • This activates Parasymp neurons causing contraction of detrusor muscle that relaxes internal urethral sphincter creating sense of urgency • There is voluntary control over external urethral sphincter • When urination is consciously initiated, descending motor tracts to micturition center inhibit somatic motor fibers of external urethral sphincter and urine is expelled 17-9

  10. Nephron 17-10

  11. Nephron • Is functional unit of kidney; responsible for forming urine • >1 million nephrons/kidney • Is a long tube and has associated blood vessels 17-11

  12. 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 17-12

  13. Renal Blood Vessels continued • Interlobular arteries give rise to afferent arterioles which supply glomeruli • Glomeruli are mass of capillaries inside glomerular capsule that gives rise to filtrate that enters nephron tubule • Efferent arteriole drains glomerulus and delivers that blood to peritubular capillaries (vasa recta) • Blood from peritubular capillaries enters veins 17-13

  14. 17-14

  15. Nephron Tubules • Tubular part of nephron begins with glomerular capsule which transitions into proximal convoluted tubule (PCT), then to descending and ascending limbs of Loop of Henle (LH), and distal convoluted tubule (DCT) • Tubule ends where it empties into collecting duct (CD) 17-15

  16. Glomerular (Bowman's) Capsule • Surrounds glomerulus • Together they form renal corpuscle • Is where glomerular filtration occurs • Filtrate passes into PCT 17-16

  17. Proximal Convoluted Tubule • Walls consist of single layer of cuboidal cells with millions of microvilli • Which increase surface area for reabsorption 17-17

  18. 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 17-18

  19. Glomerular Filtration 17-19

  20. Glomerular Filtration • Glomerular capillaries and Bowman's capsule form a filter for blood • Glomerular Caps are fenestrated--have large pores between its endothelial cells • Big enough to allow any plasma molecule to pass • 100-400 times more permeable than other Caps 17-20

  21. Glomerular Filtration continued • To enter tubule filtrate must pass through narrow slit diaphragms formed between pedicels (foot processes) of podocytes of glomerular capsule 17-21

  22. Glomerular Filtration continued • Plasma proteins are mostly excluded from the filtrate because of large size and negative charge • The slit diaphragms are lined with negative charges which repel negatively-charged proteins • Some protein (especially albumin) normally enters the filtrate but most is reabsorbed by receptor-mediated endocytosis • In some diseases, a lot of protein appears in the urine (=proteinuria) 17-22

  23. 17-23

  24. 17-24

  25. Glomerular Ultrafiltrate • Is fluid that enters glomerular capsule, whose filtration was driven by blood pressure 17-25

  26. 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 17-26

  27. Regulation of GFR • Is controlled by extrinsic and intrinsic (autoregulation) mechanisms • Vasoconstriction or dilation of afferent arterioles affects rate of blood flow to glomeruli and thus GFR 17-27

  28. Sympathetic Effects • Sympathetic activity constricts afferent arteriole • Helps maintain BP and shunts blood to heart and muscles 17-28

  29. 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 17-29

  30. 17-30

  31. Renal Autoregulation continued • Is also maintained by negative feedback between afferent arteriole and 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 17-31

  32. Function of Nephron Segments 17-32

  33. Reabsorption of Salt and H2O • In PCT returns most molecules and H2O 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) 17-33

  34. Reabsorption of Salt and H2O continued • Return of filtered molecules is called reabsorption • Water is never transported • Other molecules are transported and water follows by osmosis 17-34

  35. PCT • Filtrate in PCT is isosmotic to blood (300 mOsm/L) • Thus reabsorption of H2O 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 17-35

  36. 17-36

  37. Significance of PCT Reabsorption • ~65% Na+, Cl-, and H2O is reabsorbed in PCT and returned to bloodstream • An additional 20% is reabsorbed in descending loop of Henle • Thus 85% of filtered H2O and salt are reabsorbed early in tubule • This is constant and independent of hydration levels • Energy cost is 6% of calories consumed at rest • The remaining 15% is reabsorbed variably, depending on level of hydration 17-37

  38. Concentration Gradient in Kidney • In order for H2O to be reabsorbed, interstitial fluid must be hypertonic • Osmolality of medulla interstitial fluid (1200-1400 mOsm) is 4X that of cortex and plasma (300 mOsm) • This concentration gradient results largely from loop of Henle which allows interaction between descending and ascending limbs 17-38

  39. Descending Limb LH • Is permeable to H2O • Is impermeable to, and does not AT, salt • Because deep regions of medulla are 1400 m Osm, H2O diffuses out of filtrate until it equilibrates with interstitial fluid • This H2O is reabsorbed by capillaries 17-39

  40. Ascending Limb LH • Has a thin segment in depths of medulla and thick part toward cortex • Impermeable to H2O; permeable to salt; thick part ATs salt out of filtrate • AT of salt causes filtrate to become dilute (100 mOsm) by end of LH 17-40

  41. 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+ and 1 K+ to 2 Cl- 17-41

  42. AT in Ascending Limb LH continued • Na+ is AT across basolateral membrane by Na+/ K+ pump • Cl- passively follows Na+ down electrical gradient • K+ passively diffuses back into filtrate 17-42

  43. Countercurrent Multiplier System • Countercurrent flow and proximity allow descending and 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 H2O 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 17-43

  44. Vasa Recta • Is important component of countercurrent multiplier • Permeable to salt, H2O (via aquaporins), and urea • Recirculates salt, trapping some in medulla interstitial fluid • Reabsorbs H2O coming out of descending limb • Descending section has urea transporters • Ascending section has fenestrated capillaries 17-44

  45. Effects of Urea • Urea contributes to high osmolality in medulla • Deep region of collecting duct is permeable to urea and transports it 17-45

  46. 17-46

  47. Collecting Duct (CD) • Plays important role in water conservation • Is impermeable to salt in medulla • Permeability to H2O depends on levels of ADH 17-47

  48. 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, H2O is drawn out of CD by high osmolality of interstitial fluid • And reabsorbed by vasa recta 17-48

  49. Osmolality of Different Regions of the Kidney 17-49

  50. Renal Clearance 17-50

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