Chapter 17


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Chapter 17

  1. 1. Chapter 17 Physiology of the Kidneys 17-1
  2. 2. <ul><li>Chapter 17 Outline </li></ul><ul><li>Overview of Kidney Structure </li></ul><ul><li>Nephron </li></ul><ul><li>Glomerular Filtration </li></ul><ul><li>Function of Nephron Segments </li></ul><ul><li>Renal Clearance </li></ul><ul><li>Hormonal Effects </li></ul><ul><li>Na + , K + , H + , & HC0 3 - Relationships </li></ul><ul><li>Clinical Aspects </li></ul>17-2
  3. 3. Kidney Function <ul><li>Is to regulate plasma & interstitial fluid by formation of urine </li></ul><ul><li>In process of urine formation, kidneys regulate: </li></ul><ul><ul><li>Volume of blood plasma, which contributes to BP </li></ul></ul><ul><ul><li>Waste products in blood </li></ul></ul><ul><ul><li>Concentration of electrolytes </li></ul></ul><ul><ul><ul><li>Including Na + , K + , HC0 3 -, & others </li></ul></ul></ul><ul><ul><li>Plasma pH </li></ul></ul>17-3
  4. 4. Overview of Kidney Structure 17-4
  5. 5. Structure of Urinary System <ul><li>Paired kidneys are on either side of vertebral column below diaphragm </li></ul><ul><ul><li>About size of fist </li></ul></ul><ul><li>Urine flows from kidneys into ureters which empty into bladder </li></ul>Fig 17.1 17-5
  6. 6. Structure of Kidney <ul><li>Cortex contains many capillaries & outer parts of nephrons </li></ul><ul><li>Medulla consists of renal pyramids separated by renal columns </li></ul><ul><ul><li>Pyramid contains minor calyces which unite to form a major calyx </li></ul></ul>Fig 17.2 17-6
  7. 7. Structure of Kidney continued <ul><li>Major calyces join to form renal pelvis which collects urine </li></ul><ul><ul><li>Conducts urine to ureters which empty into bladder </li></ul></ul>Fig 17.3 17-7
  8. 8. Micturition Reflex (Urination) <ul><li>Actions of internal & external urethral sphincters are regulated by reflex center located in sacral part of cord </li></ul><ul><li>Filling of bladder activates stretch receptors that send impulses to micturition reflex center </li></ul><ul><ul><li>This activates Parasymp neurons causing contraction of detrusor muscle that relaxes internal urethral sphincter creating sense of urgency </li></ul></ul><ul><ul><li>There is voluntary control over external urethral sphincter </li></ul></ul><ul><li>When urination is consciously initiated, descending motor tracts to micturition center inhibit somatic motor fibers of external urethral sphincter & urine is expelled </li></ul>17-8
  9. 9. Nephron 17-9
  10. 10. Nephron <ul><li>Is functional unit of kidney responsible for forming urine </li></ul><ul><ul><li>>1 million nephrons/kidney </li></ul></ul><ul><li>Is a long tube & has associated blood vessels </li></ul>Fig 17.2 17-10
  11. 11. Renal Blood Vessels <ul><li>Blood enters kidney through renal artery </li></ul><ul><ul><li>Which divides into interlobar arteries </li></ul></ul><ul><ul><ul><li>That divide into arcuate arteries that give rise to interlobular arteries </li></ul></ul></ul>Fig 17.4 17-11
  12. 12. Renal Blood Vessels <ul><li>Interlobular arteries give rise to afferent arterioles which supply glomeruli </li></ul><ul><li>Glomeruli are mass of capillaries inside glomerular capsule that gives rise to filtrate that enters nephron tubule </li></ul><ul><li>Efferent arteriole drains glomerulus & delivers that blood to peritubular capillaries ( vasa recta ) </li></ul><ul><li>Blood from peritubular capillaries enters veins </li></ul>17-12
  13. 13. Fig 17.5 17-13
  14. 14. Nephron Tubules <ul><li>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 ) </li></ul><ul><li>Tubule ends where it empties into collecting duct ( CD ) </li></ul>Fig 17.2 17-14
  15. 15. Glomerular (Bowman's) Capsule <ul><li>Surrounds glomerulus </li></ul><ul><ul><li>Together they form renal corpuscle </li></ul></ul><ul><li>Is where glomerular filtration occurs </li></ul><ul><ul><li>Filtrate passes into PCT </li></ul></ul>Fig 17.6 17-15 Glomerular capsule PCT
  16. 16. Proximal Convoluted Tubule <ul><li>Walls consist of single layer of cuboidal cells with millions of microvilli </li></ul><ul><ul><li>Which increase surface area for reabsorption </li></ul></ul><ul><ul><li>Nephron Function animation </li></ul></ul>17-16
  17. 17. Type of Nephrons <ul><li>Cortical nephrons originate in outer 2/3 of cortex </li></ul><ul><li>Juxtamedullary nephrons originate in inner 1/3 cortex </li></ul><ul><ul><li>Have long LHs </li></ul></ul><ul><ul><li>Important in producing concentrated urine </li></ul></ul>Fig 17.6 17-17
  18. 18. Glomerular Filtration 17-18
  19. 19. Glomerular Filtration <ul><li>Glomerular capillaries & Bowman's capsule form a filter for blood </li></ul><ul><ul><li>Glomerular Caps are fenestrated --have large pores between its endothelial cells </li></ul></ul><ul><ul><ul><li>100-400 times more permeable than other Caps </li></ul></ul></ul><ul><ul><ul><li>Small enough to keep RBCs, platelets, & WBCs from passing </li></ul></ul></ul><ul><ul><ul><li>Pores are lined with negative charges to keep blood proteins from filtering </li></ul></ul></ul>17-19
  20. 20. <ul><li>To enter tubule filtrate must pass through narrow filtration slits formed between pedicels of podycytes of glomerular capsule </li></ul>Glomerular Filtration continued Fig 17.8 17-20
  21. 21. Fig 17.7 17-21
  22. 22. Fig 17.9 17-22
  23. 23. Glomerular Ultrafiltrate <ul><li>Is fluid that enters glomerular capsule, whose filtration was driven by blood pressure </li></ul>Fig 17.10 17-23
  24. 24. Glomerular Filtration Rate (GFR) <ul><li>Is volume of filtrate produced by both kidneys/min </li></ul><ul><ul><li>Averages 115 ml/min in women; 125 ml/min in men </li></ul></ul><ul><ul><li>Totals about 180L/day (45 gallons) </li></ul></ul><ul><ul><ul><li>So most filtered water must be reabsorbed or death would ensue from water lost through urination </li></ul></ul></ul>17-24
  25. 25. Regulation of GFR <ul><li>Is controlled by extrinsic & intrinsic ( autoregulation ) mechanisms </li></ul><ul><li>Vasoconstriction or dilation of afferent arterioles affects rate of blood flow to glomeruli & thus GFR </li></ul>17-25
  26. 26. Sympathetic Effects <ul><li>Sympathetic activity constricts afferent arteriole </li></ul><ul><ul><li>Helps maintain BP & shunts blood to heart & muscles </li></ul></ul>Fig 17.11 17-26
  27. 27. Renal Autoregulation <ul><li>Allows kidney to maintain a constant GFR over wide range of BPs </li></ul><ul><li>Achieved via effects of locally produced chemicals on afferent arterioles </li></ul><ul><li>When average BP drops to 70 mm Hg afferent arteriole dilates </li></ul><ul><li>When average BP increases, afferent arterioles constrict </li></ul>17-27
  28. 28. 17-28
  29. 29. Renal Autoregulation <ul><li>Is also maintained by negative feedback between afferent arteriole & volume of filtrate ( tubuloglomerular feedback ) </li></ul><ul><ul><li>Increased flow of filtrate sensed by macula densa (part of juxtaglomerular apparatus ) in thick ascending LH </li></ul></ul><ul><ul><ul><li>Signals afferent arterioles to constrict </li></ul></ul></ul>17-29
  30. 30. Function of Nephron Segments 17-30
  31. 31. Reabsorption of Salt & H 2 0 <ul><li>In PCT returns most molecules & H 2 0 from filtrate back to peritubular capillaries </li></ul><ul><ul><li>About 180 L/day of ultrafiltrate produced; only 1–2 L of urine excreted/24 hours </li></ul></ul><ul><ul><ul><li>Urine volume varies according to needs of body </li></ul></ul></ul><ul><ul><ul><li>Minimum of 400 ml/day urine necessary to excrete metabolic wastes ( obligatory water loss ) </li></ul></ul></ul>17-31
  32. 32. Reabsorption of Salt & H 2 0 continued <ul><li>Return of filtered molecules is called reabsorption </li></ul><ul><li>Water is never transported </li></ul><ul><ul><li>Other molecules are transported & water follows by osmosis </li></ul></ul>Fig 17.13 17-32
  33. 33. PCT <ul><li>Filtrate in PCT is isosmotic to blood ( 300 mOsm/L ) </li></ul><ul><li>Thus reabsorption of H 2 0 by osmosis cannot occur without active transport (AT) </li></ul><ul><ul><li>Is achieved by AT of Na+ out of filtrate </li></ul></ul><ul><ul><ul><li>Loss of + charges causes Cl- to passively follow Na+ </li></ul></ul></ul><ul><ul><ul><li>Water follows salt by osmosis </li></ul></ul></ul>Fig 17.14 17-33
  34. 34. Insert fig. 17.14 Fig 17.15 17-34
  35. 35. Significance of PCT Reabsorption <ul><li>≈ 65% Na + , Cl - , & H 2 0 is reabsorbed in PCT & returned to bloodstream </li></ul><ul><li>An additional 20% is reabsorbed in descending loop of Henle </li></ul><ul><li>Thus 85% of filtered H 2 0 & salt are reabsorbed early in tubule </li></ul><ul><ul><li>This is constant & independent of hydration levels </li></ul></ul><ul><ul><li>Energy cost is 6% of calories consumed at rest </li></ul></ul><ul><ul><li>The remaining 15% is reabsorbed variably, depending on level of hydration </li></ul></ul>17-35
  36. 36. Concentration Gradient in Kidney <ul><li>In order for H 2 0 to be reabsorbed, interstitial fluid must be hypertonic </li></ul><ul><li>Osmolality of medulla interstitial fluid ( 1200-1400 m O sm ) is 4X that of cortex & plasma ( 300 m O sm ) </li></ul><ul><ul><li>This concentration gradient results largely from loop of Henle which allows interaction between descending & ascending limbs </li></ul></ul>17-36
  37. 37. Descending Limb LH <ul><li>Is permeable to H 2 0 </li></ul><ul><li>Is impermeable to, & does not AT, salt </li></ul><ul><li>Because deep regions of medulla are 1400 m O sm, H 2 0 diffuses out of filtrate until it equilibrates with interstitial fluid </li></ul><ul><ul><li>This H 2 0 is reabsorbed by capillaries </li></ul></ul>Fig 17.17 17-37
  38. 38. Ascending Limb LH <ul><li>Has a thin segment in depths of medulla & thick part toward cortex </li></ul><ul><li>Impermeable to H 2 0; permeable to salt; thick part ATs salt out of filtrate </li></ul><ul><ul><li>AT of salt causes filtrate to become dilute (100 m O sm) by end of LH </li></ul></ul>Fig 17.17 17-38
  39. 39. Vasa Recta <ul><li>Is important component of countercurrent multiplier </li></ul><ul><li>Permeable to salt, H 2 0 (via aquaporins ), & urea </li></ul><ul><li>Recirculates salt, trapping some in medulla interstitial fluid </li></ul><ul><li>Reabsorbs H 2 0 coming out of descending limb </li></ul><ul><li>Descending section has urea transporters </li></ul><ul><li>Ascending section has fenestrated capillaries </li></ul>Fig 17.18 17-42
  40. 40. 17-44
  41. 41. Collecting Duct (CD) <ul><li>Plays important role in water conservation </li></ul><ul><li>Is impermeable to salt in medulla </li></ul><ul><li>Permeability to H 2 0 depends on levels of ADH </li></ul>17-45
  42. 42. ADH <ul><li>Is secreted by post pituitary in response to dehydration </li></ul><ul><li>Stimulates insertion of aquaporins (water channels) into plasma membrane of CD </li></ul><ul><li>When ADH is high, H 2 0 is drawn out of CD by high osmolality of interstitial fluid </li></ul><ul><ul><li>& reabsorbed by vasa recta </li></ul></ul>Fig 17.21 17-46
  43. 43. Renal Clearance 17-48
  44. 44. Renal Clearance <ul><li>Refers to ability of kidney to remove substances from blood & excrete them in urine </li></ul><ul><li>Occurs by filtration & by secretion </li></ul><ul><li>Secretion is opposite of reabsorption--substances from vasa recta are transported into tubule & excreted </li></ul><ul><li>Reabsorption decreases renal clearance; secretion increases clearance </li></ul>Fig 17.22 17-49
  45. 45. Secretion of Drugs <ul><li>Many drugs, toxins, & metabolites are secreted by organic anion transporters of the PCT </li></ul><ul><ul><li>Involved in determining half-life of many therapeutic drugs </li></ul></ul>17-50
  46. 46. Measurement of Renal Blood Flow <ul><li>Not all blood delivered to glomerulus is filtered into glomerular capsule </li></ul><ul><ul><li>20% is filtered; rest passes into efferent arteriole & back into circulation </li></ul></ul><ul><ul><li>Substances that aren't filtered can still be cleared by active transport (secretion) into tubules </li></ul></ul>17-55
  47. 47. Glucose & Amino Acid Reabsorption <ul><li>Filtered glucose & amino acids are normally 100% reabsorbed from filtrate </li></ul><ul><ul><li>Occurs in PCT by carrier-mediated cotransport with Na+ </li></ul></ul><ul><ul><ul><li>Transporter displays saturation if ligand concentration in filtrate is too high </li></ul></ul></ul><ul><ul><ul><ul><li>Level needed to saturate carriers & achieve maximum transport rate is transport maximum ( T m ) </li></ul></ul></ul></ul><ul><ul><li>Glucose & amino acid transporters don't saturate under normal conditions </li></ul></ul>17-58
  48. 48. Glycosuria <ul><li>Is presence of glucose in urine </li></ul><ul><li>Occurs when glucose > 180-200mg/100ml plasma (= renal plasma threshold ) </li></ul><ul><ul><li>Glucose is normally absent because plasma levels stay below this value </li></ul></ul><ul><ul><li>Hyperglycemia has to exceed renal plasma threshold </li></ul></ul><ul><ul><li>Diabetes mellitus occurs when hyperglycemia results in glycosuria </li></ul></ul>17-59
  49. 49. Hormonal Effects 17-60
  50. 50. Electrolyte Balance <ul><li>Kidneys regulate levels of Na + , K + , H + , HC0 3 - , Cl-, & PO 4 -3 by matching excretion to ingestion </li></ul><ul><li>Control of plasma Na + is important in regulation of blood volume & pressure </li></ul><ul><li>Control of plasma of K + important in proper function of cardiac & skeletal muscles </li></ul>17-61
  51. 51. Role of Aldosterone in Na + /K + B alance <ul><li>90% filtered Na + & K + reabsorbed before DCT </li></ul><ul><ul><li>Remaining is variably reabsorbed in DCT & cortical CD according to bodily needs </li></ul></ul><ul><ul><ul><li>Regulated by aldosterone (controls K + secretion & Na + reabsorption) </li></ul></ul></ul><ul><ul><ul><li>In the absence of aldosterone, 80% of remaining Na + is reabsorbed in DCT & cortical CD </li></ul></ul></ul><ul><ul><ul><li>When aldosterone is high all remaining Na + is reabsorbed </li></ul></ul></ul>17-62
  52. 52. Renin-Angiotensin-Aldosterone System <ul><li>Is activated by release of renin from granular cells within afferent arteriole </li></ul><ul><ul><li>Renin converts angiotensinogen to angiotensin I </li></ul></ul><ul><ul><ul><li>Which is converted to Angio II by angiotensin-converting enzyme ( ACE ) in lungs </li></ul></ul></ul><ul><ul><ul><li>Angio II stimulates release of aldosterone </li></ul></ul></ul>17-65
  53. 53. Regulation of Renin Secretion <ul><li>Inadequate intake of NaCl always causes decreased blood volume </li></ul><ul><ul><li>Because lower osmolality inhibits ADH, causing less H 2 O reabsorption </li></ul></ul><ul><ul><li>Low blood volume & renal blood flow stimulate renin release </li></ul></ul><ul><ul><ul><li>Via direct effects of BP on granular cells & by Symp activity initiated by arterial baroreceptor reflex (see Fig 14.26) </li></ul></ul></ul>17-66
  54. 54. Macula Densa <ul><li>Is region of ascending limb in contact with afferent arteriole </li></ul><ul><li>Cells respond to levels of Na + in filtrate </li></ul><ul><ul><li>Inhibit renin secretion when Na + levels are high </li></ul></ul><ul><ul><li>Causing less aldosterone secretion, more Na + excretion </li></ul></ul>Fig 17.26 17-68
  55. 55. 17-69
  56. 56. Atrial Natriuretic Peptide (ANP) <ul><li>Is produced by atria due to stretching of walls </li></ul><ul><li>Acts opposite to aldosterone </li></ul><ul><li>Stimulates salt & H 2 0 excretion </li></ul><ul><li>Acts as an endogenous diuretic </li></ul>17-70
  57. 57. Renal Acid-Base Regulation <ul><li>Kidneys help regulate blood pH by excreting H + &/or reabsorbing HC0 3 - </li></ul><ul><li>Most H + secretion occurs across walls of PCT in exchange for Na + (Na + /H + antiporter) </li></ul><ul><li>Normal urine is slightly acidic (pH = 5-7) because kidneys reabsorb almost all HC0 3 - & excrete H + </li></ul>17-73
  58. 58. Urinary Buffers <ul><li>Nephron cannot produce urine with pH < 4.5 </li></ul><ul><li>Excretes more H + by buffering H + s with HPO 4 -2 or NH 3 before excretion </li></ul><ul><li>Phosphate enters tubule during filtration </li></ul><ul><li>Ammonia produced in tubule by deaminating amino acids </li></ul><ul><li>Buffering reactions </li></ul><ul><ul><ul><ul><li>HPO 4 -2 + H +  H 2 PO 4 - </li></ul></ul></ul></ul><ul><ul><ul><ul><li>NH 3 + H +  NH 4 + (ammonium ion) </li></ul></ul></ul></ul>17-76
  59. 59. Clinical Aspects 17-77
  60. 60. Diuretics <ul><li>Are used to lower blood volume because of hypertension, congestive heart failure, or edema </li></ul><ul><li>Increase volume of urine by increasing proportion of glomerular filtrate that is excreted </li></ul><ul><li>Loop diuretics are most powerful; inhibit AT salt in thick ascending limb of LH </li></ul><ul><li>Thiazide diuretics inhibit NaCl reabsorption in 1 st part of DCT </li></ul><ul><li>Carbonic anhydrase inhibitors prevent H 2 0 reabsorption in PCT when HC0 s - is reabsorbed </li></ul><ul><li>Osmotic diuretics increase osmotic pressure of filtrate </li></ul>17-78
  61. 61. Kidney Diseases <ul><li>In acute renal failure , ability of kidneys to excrete wastes & regulate blood volume, pH, & electrolytes is impaired </li></ul><ul><ul><li>Rise in blood creatinine & decrease in renal plasma clearance of creatinine </li></ul></ul><ul><ul><li>Can result from atherosclerosis, inflammation of tubules, kidney ischemia, or overuse of NSAIDs </li></ul></ul>17-80
  62. 62. Kidney Diseases continued <ul><li>Glomerulonephritis is inflammation of glomeruli </li></ul><ul><ul><li>Autoimmune attack against glomerular capillary basement membranes </li></ul></ul><ul><ul><ul><li>Causes leakage of protein into urine resulting in decreased colloid osmotic pressure & resulting edema </li></ul></ul></ul>17-81
  63. 63. <ul><li>In renal insufficiency , nephrons have been destroyed as a result of a disease </li></ul><ul><ul><li>Clinical manifestations include salt & H 2 0 retention & uremia (high plasma urea levels) </li></ul></ul><ul><ul><ul><li>Uremia is accompanied by high plasma H + & K + which can cause uremic coma </li></ul></ul></ul><ul><ul><li>Treatment includes hemodialysis </li></ul></ul><ul><ul><ul><li>Patient's blood is passed through a dialysis machine which separates molecules on basis of ability to diffuse through selectively permeable membrane </li></ul></ul></ul><ul><ul><ul><li>Urea & other wastes are removed </li></ul></ul></ul>Kidney Diseases continued 17-82