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Chapter 25

Chapter 25. The Urinary System. G.R. Pitts, J.R. Schiller, and James F. Thompson, Ph.D. General. During metabolism cells produce wastes waste - any substance acquired or produced in excess with no function in body e.g. - CO 2 , H 2 O, heat

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Chapter 25

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  1. Chapter 25 The Urinary System G.R. Pitts, J.R. Schiller, and James F. Thompson, Ph.D.

  2. General • During metabolism cells produce wastes • waste - any substance acquired or produced in excess with no function in body • e.g. - CO2, H2O, heat • All wastes must be eliminated, or at least maintained at low concentrations • Additionally, protein breakdown leaves nitrogenous wastes • Excess sodium (Na+), chloride (Cl-), potassium (K+), sulfate (SO42-), phosphate (PO42-), and hydrogen ion (H+) must be regulated

  3. General • Several organs transport, neutralize, store and remove wastes • Body fluid and body fluid buffers • Blood and blood buffers • Liver • Lungs • Sudoriferous (sweat) glands (minor) • Hair and nails (minor) • GI tract and liver • Kidneys

  4. General • Urinary system • Maintains fluid homeostasis including: • regulation of volume and composition by eliminating certain wastes while conserving needed materials • regulation of blood pH • regulation of hydrostatic pressure of blood and, indirectly, of other body fluids • Contributions to metabolism • helps synthesize calcitriol (active form of Vitamin D) • secretes erythropoietin • performs gluconeogenesis during fasting or starvation • deaminates certain amino acids to eliminate ammonia

  5. Kidneys • Paired reddish organs, just above waist on posterior wall of abdomen • partially protected by 11th, 12th ribs • right kidney sits lower than the left kidney • receive 20-25% of the resting cardiac output • Consume 20-25% of the O2 used by the body at rest

  6. Kidneys (cont.) • Retroperitoneal, as are ureters and urinary bladder

  7. Kidney - Internal Gross Anatomy Know these terms for lecture and lab exams!

  8. Kidney - Internal Micro Anatomy • Nephron – the functional unit of kidney • Three physiological processes: 1) filtration, 2) reabsorption , and 3) secretion • These three processes cooperate to achieve the various functions of the kidney • Different sites different primary functions

  9. The Functions of the Kidney • Nephron forms urine from blood plasma • 1) formation of a plasma filtrate • 2) reabsorption of useful molecules from the filtrate to prevent their loss in urine • 3) secretion of excess electrolytes and certain wastes (nitrogenous wastes, H+) in concentrations greater than their concentration in plasma • 4) regulation of water balance by concentrating or diluting the urine • 5) minor endocrine function – releasing hormone erythropoietin to stimulate RBC production • 6) releasing renin for angiotensinogen activation

  10. Kidney - Internal Micro Anatomy • ~A million nephrons are located in the cortex • The filtrate is carried by the collecting duct system through the medulla • The urine is collected at the papillae into the minor and major calyxes Nephron Papilla Minor Calyx

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

  12. Nephron • Renal corpuscle • site of plasma filtration • 2 components • glomerulus • tuft of capillary loops • fed by afferent arteriole • drained by efferent arteriole • glomerular (Bowman's) capsule • double walled cup lined by simple squamous epithelium • outer wall (parietal layer) separated from inner wall (visceral layer = podocytes) by capsular (Bowman's) space • as blood flows through capillary tuft – filtration occurs • water and most dissolved molecules pass into capsular space • large proteins and formed elements in the blood do not cross

  13. 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 pap ducts/papillae DCT PCT ducts Loop

  14. Nephron • Cortical vs. juxtamedullary nephrons • Location related to the length of loop of the nephron • 15-20% of the nephrons have longer loops and increased involvement inthe reabsorption of water H2O

  15. Renal Corpuscle Histology • Each nephron portion has distinctive features • Histology of the glomerular filtration membrane • Three components to the filter • From inside to out, the layers prevent movement of progressively smaller particles

  16. Histology of Filtration Membrane • Endothelium of glomerulus • Single layer of capillary endothelium with fenestrations • Prevents RBC passage; WBCs use diapedesis to get out

  17. Histology of Filtration Membrane • Basement membrane of glomerulus • Between endothelium and visceral layer of glom. capsule • Prevents passage of large protein molecules

  18. Histology of Filtration Membrane • Filtration slits in podocytes • Podocytes • specialized epithelium of visceral layer • footlike extensions with filtration slits between extensions • Restricts passage of medium-sized proteins

  19. Histology of Filtration Membrane

  20. Tubule Histology • PCT - cuboidal cells with apical microvilli • Descending Loop, and beginning of Ascending Loop • simple squamous epithelium • water permeable • Remainder of Ascending limb of the Loop • cuboidal to low columnar epithelial cells • impermeable to water • permeable to solute (ions) • DCT, collecting ducts • cuboidal with specialized cells • principal cells - sensitive to ADH (antidiuretic hormone) • intercalated cells - secrete H+

  21. Renal Blood Supply • Important vessels • Renal arteries • 20-25% of resting CO • 1200 ml/min • Segmental arteries • Interlobar arteries - through columns • Arcuate arteries • Interlobular arteries Refer to the kidney models in lab.

  22. Renal Blood Supply peritubular capillaries • Important vessels • Afferent arterioles - each renal corpuscle receives one • Glomerular capillaries • Efferent arterioles - drain blood from glomerulus cortex -------- medulla • Peritubular capillaries - around cortical nephrons • Vasa recta - long networks from the efferent arteriole around the Loop (juxtamedullary nephrons) Vasa recta

  23. Renal Blood Supply • Important vessels • Interlobular veins • Arcuate veins • Interlobar veins • Segmental veins • Renal veins - exits hilus Refer to the kidney models in lab.

  24. Renin-Angiotensin System • Juxtaglomerular apparatus (JGA) • Distal tubule contacts afferent arteriole at renal corpuscle • Juxtaglomerular (JG) cells • modified smooth muscle cells in afferent arteriole wall detect changes in blood pressure (a stretch reflex) • Secrete enzyme renin to trigger Renin-Angiotensin System if blood pressure falls JG afferent art. efferent art. Distal Convoluted Tubule

  25. Renin-Angiotensin System • Juxtaglomerular apparatus (JGA) • Distal tubule contacts afferent arteriole at renal corpuscle • Macula Densa (MD) cells • special cells in the wall of the distal tubule in this area monitor the osmotic potential in the filtrate in the distal tubule • stimulate JG cells to release renin if filtrate is too dilute, indicating insufficient filtration and/or low blood pressure/low blood volume • Both JG and MD cells work together to regulate blood pressure and blood volume JG afferent art. MD efferent art. Distal Convoluted Tubule

  26. Renin-Angiotensin System • Hepatocytes secrete inactive precursor Angiotensinogen into the bloodstream • Juxtaglomerular (JG) cells secrete the enzyme reninto convert Angiotensinogen to Angiotensin I in the bloodstream • Angiotensin I is transported to the lungs where Angiotensin Converting Enzyme (ACE) converts Angiotensin I to Angiotensin II • Both Angiotensin I and Angiotensin II act as circulating hormones to increase blood pressure and blood volume; AII is stronger

  27. Renal Nerve Supply • Nerves from renal plexus of Sympathetic Division of ANS innervate the kidney • Vasomotor nerves accompany the renal arteries and their branches • What is the role of sympathetic stimulation on renal blood flow? • In “Fight or Flight” or muscular exertion: • decrease renal arterial flow • decrease urine production • maintain blood volume • increase systemic blood pressure

  28. Physiology of Urine Formation • Glomerular filtration - first step in urine formation • forcing of fluids and dissolved solutes through membrane by hydrostatic pressure • same process as in systemic capillaries • results in a filtrate • 180 L/day, about 60 times plasma volume • 178-179 L/day is reabsorbed (~99%) 1-2 L/day of urine is typical

  29. Glomerular Filtration • 3 structural features of the renal corpuscles enhance their filtering capacity: • Glomerular capillaries are relatively long which increases theirsurface area for filtration • Filter (endothelium-capsular membrane) is thin and porous • Fenestrated glomerular capillaries are 50 times more permeable than regular capillaries • The filtration slits of the basement membrane only permit passage of small molecules • Glomerular Capillary blood pressure is high – the efferent arteriole diameter is less than the afferent arteriole diameter -- increasing filtration pressure in the renal corpuscle

  30. Glomerular Filtration • Net filtration pressure (NFP) depends on 3 pressures: • glomerular blood hydrostatic pressure (GBHP) • capsular hydrostatic pressure (CHP) • blood colloid osmotic pressure (BCOP) NFP = GBHP – CHP – BCOP 10 = 55 - 15 - 30 1 2 3

  31. Glomerular Filtration Rate (GFR) • GFR • Volume of filtrate that forms in all renal corpuscles in both kidneys/min • Adult’s GFR 125 mL/min (180 L/day) • Regulation of GFR • When more blood flows into glomerulus, GFR  • GFR depends on systemic blood pressure, and the diameter of afferent & efferent arterioles • If glomerular capillary blood pressure falls much below 45 mm Hg, no filtration occurs  anuria (no urine output)

  32. Glomerular Filtration Rate (GFR) • 3 principal regulators of GFR: • Renal autoregulation of GFR • the kidneys are able to maintain a relatively constant internal blood pressure and GFR despite changes in systemic arterial pressure • there is negative feedback from the JuxtaGlomerular Apparatus adjusting blood pressure and blood volume

  33. Glomerular Filtration Rate (GFR) • 3 principal regulators of GFR (cont.): • Hormonal regulation of GFR • Angiotensin I & II • activated by renin released from JG cells and further by ACE in the lungs • 5 important functions • direct vasoconstriction •  aldosterone secretion •  thirst generated at the hypothalamus •  ADH secretion •  Na+ reabsorption (H2O follows passively) • Net Effect  increased blood pressure and blood volume

  34. Glomerular Filtration Rate (GFR) • 3 principal regulators of GFR (cont.): • Hormonal regulation of GFR • Angiotensin I & II • Atrial Natriuretic Peptide (ANP) • secreted by cells in atria of heart in response to stretch •  GFR, promotes excretion of H2O, Na+, but retention of K+ • suppresses output of ADH, aldosterone, and renin • Net Effect  decreased blood pressure and blood volume • Aldosterone • secreted by cells in adrenal cortex in response to angiotensin I & II (and ACTH) •  GFR, promotes retention of H2O, Na+, but excretion of K+ • antagonist to Atrial Natriuretic Peptide • Net Effect  increased blood pressure and blood volume

  35. Glomerular Filtration Rate (GFR) • 3 principal regulators of GFR (cont.): • Neural regulation • kidney’s blood vessels supplied by vasoconstrictor fibers from Sympathetic Division of ANS which release Norepinephrine • strong sympathetic stimulation causes JG cells to secrete renin and the adrenal medulla to secrete Epinephrine

  36. GFR Control modest

  37. Tubular Reabsorption • Movement of water and certain solutes back into bloodstream from the renal tubule • Filter 180 L/day of fluid and solutes • nutrients (Na+, K+, Glucose, etc.) are needed by body • body will expend ATP to get them back into blood • about 99% of the filtrate volume is reabsorbed from the tubule by active transport and osmosis • Epithelial cells in PCT (microvilli) increase surface area for tubular reabsorption • DCT and collecting ducts play a lesser role in nutrient/solute reabsorption

  38. Reabsorption of Na+ in PCT • PCT is site of most electrolyte reabsorption • Mechanisms which aid Na+ transport • Na+/ K+ ATPase on basolateral side is fundamental • Concentration of Na+ inside the tubular cells is low • Interior of the cell negatively charged • Double gradient for Na+ movement from filtrate to tubular cell • Requires ATP energy

  39. Reabsorption of Nutrients in PCT • ~100% of the filtered glucose and other sugars, AA's, lactic acid, and other useful metabolites are reabsorbed • Na+ symporters power secondary active transport systems • Why secondary? They rely on the Na+/ K+ ATPase pump.

  40. Reabsorption of Na+ in PCT • Na+ is passively transported from the filtrate in tubule lumen into tubular cells to replace the Na+ being actively transported into the peritubular capillaries. Glucose moves with Na+.

  41. Reabsorption of H2O in PCT • H2O follows Na+ passively by osmosis from the filtrate through the tubular cells into the peritubular capillaries

  42. Reabsorption of Nutrients in PCT • The movement of water back to the bloodstream concentrates the remaining solutes in the filtrate [H2O]  [solutes] 

  43. Reabsorption of Nutrients in PCT • The new concentration gradients increase the diffusion of some of the other remaining solutes in the filtrate from lumen to the blood stream.

  44. Transport Maximums (Tm)’s • each type of symporter has an upper limit (maximum) on how fast it can work • any time a substance is in the filtrate in an amount greater than its transport maximum, some of it will be left behind in the urine • only Na+ has no transport maximum because Na+ is being actively transported by the Na+/ K+ ATPase pump at all times.

  45. Renal Thresholds • The Renal Threshold is the plasma concentration at which a substance begins to spill into the urine because its Tm has been surpassed. • If the plasma filtrate concentration is too high, all of the substance cannot be reabsorbed. • For example, glucose spills into the urine in untreated diabetics. • Tm for glucose = 375 mg/min • If blood glucose > 400 mg/100 mL, large quantities of glucose will appear in the urine

  46. Reabsorption in the PCT • By the end of the PCT the following reabsorption has occurred: • 100% of filtered nutrients (sugars, albumin, amino acids, vitamins, etc.) • 80-90% of filtered HCO3- • 65% of Na+ ions and water, • 50% of Cl- and K+ions

  47. Reabsorption in Loop of Henle • Cells in the thin descending limb are only permeable to water • H2O reabsorption is not coupled to reabsorption of filtered solutes (osmosis) in this area as it had been in the PCT • [Note: illustration at right is not thin descending limb of nephron loop]

  48. Reabsorption in Loop of Henle • Cells in the thicker ascending Loop feature sodium-potassium-chloride symporters • reabsorb 1 Na+, 1 K+, 2 Cl- • depend on the low cytoplasmic Na+ concentration to function • little or no H2O is reabsorbed from the thick ascending Loop • Loop reabsorbs 30% of K+, 20% of Na+, 35% of Cl-, and 15% of H2O • H2O reabsorption is not coupled to reabsorption of filtered solutes (osmosis)

  49. Reabsorption in DCT and Collecting Ducts • Filtrate reaching the DCT has already had ~80% of the solutes and H2O reabsorbed • Fluid now has the characteristics of “urine” • DCT is the site of final adjustment of urine composition • less work to do, so no need for microvilli = brush border to increase surface area for tranporters • Na+/K+/Cl- symporter is a major DCT transporter • DCT reabsorbs another 10% of filtrate volume

  50. Reabsorption in DCT and Collecting Duct • Principal cells are present in the distal DCTs and collecting ducts • 3 hormones act on principal cells to modify ion and fluid reabsorption • [1] Anti-Diuretic Hormone (ADH) (from neurohypophysis) •  H2O reabsorption by increasing permeability to H2O in the DCT and collecting duct • details discussed later on

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