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Chapter 26

Chapter 26. The Urinary System. General. Kidney functions Blood ionic composition - Na + , Cl - , sulfate (SO 4 2- ), phosphate (PO 4 2- ) Blood pH – physical removal of H + Blood volume – fluid volume regulation Blood pressure - renin Blood osmolarity – ions and fluid levels

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Chapter 26

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  1. Chapter 26 The Urinary System

  2. General • Kidney functions • Blood ionic composition - Na+, Cl-, sulfate (SO42-), phosphate (PO42-) • Blood pH – physical removal of H+ • Blood volume – fluid volume regulation • Blood pressure - renin • Blood osmolarity – ions and fluid levels • Hormone production • Calcitrol • Erythropoietin • Blood glucose levels - gluconeogenesis • Waste removal • Ammonia and urea from deamination • Bilirubin from hgb • Creatinine • Uric acid

  3. Kidney – Internal Macro Anatomy • Hilus • Cortex • Medulla • Pyramid • Column

  4. Kidney - Internal Micro Anatomy • Nephron - functional unit of kidney • 3 functions: • filtration • reabsorption • secretion • Different sites different functions: renal corpuscle, renal tubule, collecting duct, peritubular capillaries

  5. 1. Renal Corpuscle 2. Renal Tubule Nephron • 2 major parts to the nephron

  6. Nephron • Renal corpuscle • Site of fluid filtration • 2 components • Glomerulus • group of capillary loops • blood in by afferent arteriole • blood out by efferent arteriole • Glomerular (Bowman's) capsule • double walled epithelial cup • outer wall (parietal layer) separated from inner wall (visceral layer) by capsular (Bowman's) space • As blood flows through capillary - capillary filtration • Water, most solutes pass into capsular space • Large proteins, formed elements from blood do not pass

  7. Nephron • Renal tubule - where filtered fluid passes from capsule • Proximal convoluted tubule (PCT) • Loop of Henle (nephron loop) • Distal convoluted tubule (DCT) • Short connecting tubules • Collecting ducts • Merge to papillary duct • Then to minor calyx • 30 papillary ducts/papillae

  8. Renal Corpuscle Histology • Each nephron portion has distinctive features • Histology of Glomerular filter • Three layers of tissue • From inside to out prevents movement of progressively smaller particles

  9. Physiology of Urine Formation • Glomerular filtration - first step in urine formation • forcing of fluids, dissolved substances through membrane by pressure • same as in caps • results in filtrate • 180 L/day, about 60x plasma volume • 178-179 L/day reabsorbed

  10. Glomerular Filtration • Net filtration pressure (NFP) - depends on 3 pressures: • glomerular blood hydrostatic pressure (GBHP) • capsular hydrostatic pressure (CHP) • blood colloid osmotic pressure (BCOP) 1 3 2

  11. Glomerular Filtration • 3 structural features of renal corpuscles enhance filtering capacity: • Glomerular caps very long - surface area for filtration • Filter (endothelium-capsular membrane) is porous, thin • glomerular caps 50x more permeable than regular cap • basement membrane, filtration slits only permit passage of small molecules • Cap BP high - efferent arteriole < diameter afferent art -  filtration pressure

  12. Glomerular Filtration Rate (GFR) • GFR • Amount of filtrate that forms in all renal corpuscles in both kidneys/min • Adults GFR 125 ml/min (180 L/day) • Regulation of GFR • When more blood flows into glomerulus GFR  • Glomerular blood flow (GBF) depends on systemic blood pressure, diameter of afferent/efferent arterioles • If BP falls to where glomerular capillary pressure is 42 mmHg, no filtration, anuria

  13. Tubule Histology • Juxtaglomerular apparatus (JGA) • Ascending LofH contacts afferent arteriole • Macula Densa • special cells in this area monitor Na+Cl- content in filtrate • able to work w/ JG cells • Juxtaglomerular (JG) cells • modified smooth muscle • secrete vasodilators • Both work together to regulate BP

  14. Glomerular Filtration Rate (GFR) • 3 principal regulators of GFR: • Renal autoregulation of GFR • ability of kidneys to maintain a constant BP and GFR despite changes in systemic AP • high bp causes afferent arteriole to constrict – keeps GBF constant • negative feedback from JGA – high delivery of filtered Na+ and Cl- to macula densa causes constriction of afferent arteriole (decrease release of vasodilators)

  15. Glomerular Filtration Rate (GFR) • 3 principal regulators of GFR (cont.): • Hormonal regulation of GFR • Angiotensin II • catalyzed from angiotensinogen by renin released from JGA cells • 4 important functions • vasoconstriction (of afferent arteriole) •  aldosterone •  thirst •  ADH •  Na+ reabsorption • ANP • secreted by cells in atria of heart in response to stretch •  GFR by “relaxing” glomerular cap, promotes excretion of H2O, Na+ • suppresses ADH, aldosterone, renin

  16. Glomerular Filtration Rate (GFR) • 3 principal regulators of GFR (cont.): • Neural regulation • vessels of kidney supplied by vasoconstrictor fibers from SNS, with strong stim afferent constricts more than efferent • strong SNS stim causes JGA cells to secrete renin and adrenal medulla to secrete Epi

  17. Tubular Reabsorption • Movement of water, solutes back into tubule • Filter 180 L/day of fluid and solutes • filtering is non-specific • much of this (Na+, K+, Glucose, etc.) needed by body • must get them back into blood • about 99% of filtrate reabsorbed in tubule • Epithelial cells in PCT  surface area (microvilli) for reabsorption – most (65%) reabsorption occurs in PCT • DCT and collecting ducts fine tune reabsorption

  18. Reabsorption of Na+ in PCT • PCT site of most reabsorption - more Na+ ions filtered than all but H2O • Mechanisms that aid Na+ reabsorption • Na+/ K+ ATPase on basolateral side very important • Keep concentration of Na+ inside tubule cells low • Keep interior of cell negatively charged • Double gradient for Na+ movement into cell • Requires E!

  19. Reabsorption of Nutrients in PCT • 100% of filtered glucose, AA's, lactic acid, other useful metabolites reabsorbed by Na+ symporters - secondary active transport • Why are these secondary active transporters?

  20. Reabsorption of Na+ • Na+ passively diffuses from fluid in tubule lumen into cells • pulls other solutes with it via secondary active transport •  reabsorption of water (osmosis – following solutes) •  [ ] of remaining solutes •  diffusion from lumen into tubular epithelium of remaining solute •  reabsorption of water (osmosis – following solutes)

  21. Reabsorption of Nutrients • Transport maximum (Tm) • each type of symporter has upper limit on how fast it can work • work is transport of solutes • upper limit is max concentration that can still be transported out of tubule, reabsorbed • anything above max is lost in the urine • Renal threshold • plasma concentration at which a substance begins to spill into urine because Tm has been surpassed • renal tubule concentration too high, all cannot be reabsorbed by transporters • glucose and diabetics

  22. Reabsorption in the PCT • By the end of the PCT the following reabsorption has occurred: • 100% of filtered nutrients • 80-90% of filtered HCO3- • 65% of Na+ and water, • 50% of Cl- and K+

  23. Reabsorption in Loop of Henle • Cells in thin descending limb only permeable to water • No solute movement out of thin descending limb

  24. Reabsorption in Loop of Henle • Cells in thick ascending LofH feature symporters • reabsorb 1 Na+, 1 K+, 2 Cl- • dependent on lo [Na+] for function • little or no H2O reabsorbed from thick ascending LofH • Creates high osmotic concentration in kidney medulla • L of H reabsorb 30% of K+ , 20% of Na+ , 35% of Cl- , 15% of H2O • H2O reabsorption not coupled to reabsorb of filtered solutes (osmosis) • “Back side sets up the front”

  25. Reabsorption in DCT, Collecting Duct • Filtrate reaching DCT has 80% filtered solutes, H2O reabsorbed • DCT • Na+/ Cl- symporter • Ca++ reabsorbed here due to PTH • reabsorbs another 10-15% of filtrate

  26. Reabsorption in DCT, Collecting Duct • Principal cells present in late DCT and collecting duct • 2 hormones act on principal cells to modify ion and fluid reabsorption • Aldosterone • renin, angiotensin system •  Na+ reabsorption •  principal cell basolateral Na+/K+ ATPases • Anti-Diuretic Hormone (ADH) • generally principal cells have low H2O permeability • hypothalamus monitors osmotic concentration, if conc  release ADH through post. pituitary •  H2O reabsorption • adds H2O pores to apical membrane to increase H2O permeability

  27. Reabsorption Summary

  28. Tubular Secretion • Removes substances from blood, add to filtrate - includes K+, ammonium (NH4+), creatinine, penicillin • Two primary functions • Helps rid body of substances, generally waste products • Regulate blood pH by secretion of H+

  29. Secretion of K+ • Principal cells in collecting ducts secrete variable amount of K+ due to leaky channels in apical membrane+ (opposite of Na+ reabsorption) • Na+/K+ ATPases in basolateral membrane • Controlled by: • Aldosterone -  aldo,  K+ secretion • K+ concentration in plasma -  levels,  secretion • Na+ levels in DCT - high levels Na+, Na+ reabsorption,  K+ secretion

  30. Secretion of H+ • Cells of renal tubule can  blood pH 3 ways • Secrete H+ into filtrate • Reabsorb filtered HCO3- • Produce more HCO3-

  31. Secretion of H+ • In PCT • CO2 present in cell • carbonic anhydrase works in cell • end with HCO3- and H+ • Na+/H+ exchanger - H+ secondary transport with Na+ reabsorption • combines w/ HCO3- in lumen forms CO2 and H2O • CO2 diffuses back in tubule cell for more HCO3- formation • HCO3- moves back to blood by facilitated transport • Exchanger stimulated by AII for increased Na+ reabsorption

  32. Secretion of H+ • Collecting ducts can secrete H+ • Primary active transport • Generate 1000 fold concentration gradient (drop pH by 3 units) • Carbonic anhydrase • Bicarb scavenged by HCO3-/Cl- antiporter • basolateral • new HCO3- • H+ trapped in tubule lumen by buffers

  33. Secretion of NH3 and NH4+ • Ammonia (NH3) poisonous waste picked up from deamination, generally converted to urea, much less toxic • Can be used as a buffer for H+ to form NH4+ (ammonium) • PCT cells can deaminate and secrete NH4+ in a Na+/NH4+ antiporter when blood pH lo

  34. Summary of Nephron Functions

  35. Summary of Nephron Functions

  36. Summary of Nephron Functions

  37. Summary of Nephron Functions

  38. Summary of Nephron Functions

  39. Producing Dilute Urine • Rate of H2O lost from body dependent on ADH • Mechanism of Urine dilution - No ADH! • Normal concentration in PCT is 300 mOsm/L • Glomerular filtrate isosmotic to plasma • Thick ascending LofH impermeable to water but reabsorbs ions • More ions absorbed in DCT creating hypo-osmotic (hypotonic) urine

  40. Producing Concentrated Urine •  amount of water reabsorbed - make hyperosmotic (hypertonic) urine • Solute and Water Reabsorption • LofH • Collecting duct - in presence of ADH, water moves out • Urea recycling

  41. Producing Concentrated Urine • Countercurrent mechanism • Anatomical arrangement of juxtamedullary nephrons and vasa recta • U-shaped tubes have flow in opposite directions • Descending limb impermeable to ions, permeable to H2O ascending vice-versa • Overall effect • filtrate more concentrated as it flows down descending limb • more dilute as it moves up ascending limb

  42. Producing Concentrated Urine • Countercurrent mechanism • Also, Na+, K+, Cl- build up osmotic gradient in medulla of kidney • Vasa recta also consist of descending/ascending portions • Helps to remove some of the solutes w/out destroying the gradients

  43. Producing Concentrated Urine

  44. The Final Common Pathway • Ureter • extension of kidney pelvis • enter bladder medially from posterior • Physiology • transport urine to bladder • peristalsis primarily, but hydrostatic pressure gravity help

  45. Micturition • Voluntary and involuntary nerve impulses drive process • 700-800 ml capacity • When volume > 200-400 ml stretch receptors fire • Processed in cortex • micturition reflex • initiate a conscious desire to expel urine • PNS driven • Contraction of detrusor, relaxation of internal sphincter A B 2 1 3

  46. The Final Common Pathway • Urethra • Physiology - terminal portion of urinary tract, in males also serves as duct through which semen is discharged from the body • Urine • Volume • 1000-2000 ml/day • influenced by blood pressure, blood osmotic pressure, diet, temperature, diuretics, mental state, general health • Chemical Composition - 95% water, 5% solutes

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