URINARY SYSTEM. Primary functions. Major organs & structures

Transcription

1 URINARY SYSTEM Primary functions Excretion of metabolic wastes Regulation of water and ion balances Regulation of blood pressure Vitamin D activation Regulation of rbc s (erythropoietin) Gluconeogenesis Major organs & structures Kidneys Ureters Urinary bladder Urethra See Fig

2 Daily intake / output Balanced Body Fluids Tab

3 Body Fluids Fluid totals ~ 60% body weight ~ 42 L (70 kg male) Major compartments Intracellular fluid ~ 67% Interstitial fluid ~ 26% Plasma ~ 7% Fig

4 Body Fluids Comparison of substance concentrations 4 Table. 25-2, Figs. 25-2,3

5 Osmosis? Osmosis & Osmotic Equilibrium Diffusion of H 2 O through a semipermeable membrane from low solute conc. to high solute conc. Fig

6 Osmosis & Osmotic Equilibrium Effect of solutions on cells Isotonic Hypertonic Hypotonic Figs. 25-5,6 6

7 Osmoles Osmosis & Osmotic Equilibrium Describes total number of solute particles in solution (regardless of composition) 1 osm = 1 mole (6.02x10 23 ) of solute particles Typically expressed a milliosmoles (mosm) 1 osm = 1000 mosm Osmolarity Osmolar concentration of solution = osm/l solution Osmolality Osmolal concentration of solution = osm/kg H 2 0 7

8 Osmosis & Osmotic Equilibrium Osmotic pressure The amount of pressure required to prevent osmosis (pressure opposing osmosis) Directly proportional to number of osmotically active particles in solution particle concentration osmotic pressure 8

9 Osmosis & Osmotic Equilibrium van t Hoff s law Relates osmotic pressure & osmolarity = CRT = osmotic pressure C = solute concentration (osm/l) R = ideal gas constant (mmhg) T = normal body temp (310 K) At 1 mosm/l, = 19.3 mmhg for every 1 mosm gradient across a membrane, 19.3 mmhg osmotic pressure exerted p

10 Application Osmosis & Osmotic Equilibrium What is the potential osmotic pressure of physiological saline (0.9% NaCl)? 0.9% NaCl = 0.9g/100ml or 9g/L 9g/L NaCl MW (58.5 g/mol) = mol/l Osmolarity (osm/l) = mol/l x 2 = osm/l = 308 mosm/l Each molecule of NaCl = 2 osmoles (Na + + Cl - ) Osmotic pressure = 308 mosm/l x 19.3 mmhg/mosm/l = 5944 mmhg p

11 Gross Anatomy of the Kidney Capsule Renal cortex Contains renal corpuscles Renal medulla Segmented into lobes (renal pyramids) Groups of collecting ducts draining to renal pelvis Renal calyces Renal pelvis Ureter Fig

12 Gross Anatomy of the Kidney Blood supply Renal artery & vein (at hilum) Interlobar arteries & veins Arcuate arteries & veins Feed / drain nephrons Interlobular arteries & veins Blood flow Receive ~22% of cardiac output (1,100 ml/min) See Fig

13 The Nephron Primary functional unit of the kidney ~ 1x10 6 / kidney but highly variable Fig

14 Renal corpuscle Glomerulus The Nephron Capillary with afferent & efferent arterioles Site of filtration membrane Bowman s capsule Surrounds glomerulus Collects filtrate 14 Fig. 26-4

15 Tubules The Nephron Proximal tubule Reabsorption of most nutrients Active: ex., glucose, aa s, Na + Passive: Cl -, H 2 O Fig

16 Tubules The Nephron Loop of Henle Descending: H 2 O reabsorption Ascending: Na +, Cl -, K + reabsorption Fig

17 Tubules The Nephron Distal tubule Reabsorption/secretion of Na +, Cl - Site of aldosterone activity Fig

18 Collecting ducts The Nephron Reabsorption of H 2 0, urea Site of ADH activity ~250/kidney; ~4,000 nephrons each Fig

19 Capillary beds Glomerulus Arterial capillary bed Peritubular capillaries Surround renal tubules Reclaim filtrate Some secretion The Nephron Fig

20 Categories Cortical nephrons 85% Almost entirely in cortex The Nephron Fig

21 The Nephron Categories Juxtamedullary nephrons Close to cortexmedullary junction L of H extend deep into medulla Important in concentrating urine Peritubular capillaries surrounding L of H modified (vasa recta) Fig

22 Urine Formation The ultimate garage sale: Filtration Reabsorption Secretion Excretion Take out everything that fits through the door Bring back everything you want Take back out XS items Everything left goes 22

23 Urine Formation Filtration Reabsorption Secretion Excretion Excretion = Filtration Reabsorption + Secretion nephron function Fig

24 Urine Formation Not all substances treated equally A = freely filtered, not reabsorbed B = freely filtered, partly reabsorbed C = freely filtered, completely reabsorbed D = freely filtered, secreted E = not filtered, not secreted 24 Fig. 26-9

25 Blood flow Filtrate Glomerular Filtration ~1.1 L/min (~1,600 L/day) ~180 L/day Process entire plasma volume ~60x/day Urine formation ~1.5 L/day (<1% of filtrate) Why the need for the high filtration rate? 25

26 Anatomy of the Filtration Apparatus Blood supply through afferent & efferent arterioles Maintain & regulate pressure Efferent arteriole Smaller diameter resistance 26 Fig

27 Anatomy of the Filtration Apparatus Filtration membrane Fenestrated capillary epithelium Passage of fluids & small solutes 27 Fig

28 Anatomy of the Filtration Apparatus Podocytes Feet attach to endothelium Spaces between form slit pores Passage of filtrate to capsular space See Fig

29 Podocytes 29

30 Glomerular Filtration Essentially a passive process Fluids/solutes forced out by hydrostatic pressure Filterability based on Size of molecule Pores ~8 nm diameter Molecules <3 nm, freely pass E.g., water, glucose, aa s, N-wastes Molecules >7-9 nm, usually blocked 30

31 Substance Filterability Based on MW Substance MW Filterability Water Sodium Glucose Myoglobin 17, Albumin 69, See Tab

32 Glomerular Filtration Essentially a passive process Fluids/solutes forced out by hydrostatic pressure Filterability based on Size of molecule Charge of molecule (+) filtered easier than (-) of same size Proteoglycans (- charged) on surfaces of Plasma membranes of capillaries Plasma membranes of Podocytes Within basement membrane E.g., albumin ~6 nm (small enough) but not filtered (- charged) Fig

33 Glomerular Filtration Forces favoring filtration Glomerular hydrostatic pressure (P G ) ~60 mmhg Fig

34 Glomerular Filtration Forces opposing filtration Bowman s capsule hydrostatic pressure (P B ) ~18 mmhg Glomerular colloid osmotic pressure ( G ) ~32 mmhg Fig

35 Net filtration pressure Glomerular Filtration NFP = P G - P B - G ~10 mmhg Fig

36 Glomerular Filtration Rate (GFR) GFR = K f x NFP K f = glomerular capillary filtration coefficient Reflects conductivity & capillary surface area K f = GFR / NFP Normal GFR GFR (both kidneys) ~125 ml/min (~180 L/day) NFP ~10 mmhg K f ~12.5 ml/min/mmhg 36

37 K f = GFR NFP Factors Affecting GFR Reduction in glomerular capillaries Increased thickness of glomerular capillary membrane P G = GFR arterial pressure, sympathetic activity P B = GFR Urinary tract obstruction G = GFR plasma proteins See Table

38 Factors Affecting GFR arterial resistance efferent arteriole resistance Increases resistance to outflow blood pressure glomerular hydrostatic pressure (P G ) GFR Fig

39 Factors Affecting GFR arterial resistance afferent arteriole resistance Restricts blood flow to glomerulus blood pressure glomerular hydrostatic pressure (P G ) GFR Fig

40 Regulation of Filtration Intrinsic control mechanisms (autoregulation) Maintain relatively constant GFR under normal daily arterial pressure fluctuations Prevents excessive / inadequate urine production that would accompany large changes in GFR Tubuloglomerular feedback mechanism Control GFR based on glomerular pressure and NaCl concentrations Extrinsic control mechanisms ANS 40

41 Tubuloglomerular Feedback Mechanism Involves specialized tubular arrangement Juxtaglomerular apparatus (JGA) Juxtaglomerular cells Walls of afferent (1 0 ) & efferent arterioles 41 Fig

42 Tubuloglomerular Feedback Mechanism Involves specialized tubular arrangement Juxtaglomerular complex Juxtaglomerular cells Macula densa Initial portion of distal tubule Close contact with afferent/efferent arterioles 42 Fig

43 Juxtaglomerular Cells Modified smooth muscle Produce & store renin Respond to pressure changes Decreased arterial pressure promotes renin release Angiotensin II constricts efferent arterioles Results in glomerular hydrostatic pressure Figs. 19-9,

44 Macula Densa Sense changes in volume via changes in Na + & Cl - concentrations Decreased flow through L of H Slower flow Increased ion reabsorption Decreased ion concentration in filtrate Response to Na + & Cl - Vasodilate afferent arterioles Stimulate renin release from JG cells Vasoconstriction of efferent arterioles Results in glomerular hydrostatic pressure 44

45 Tubuloglomerular Feedback Overview Fig

46 Autonomic Control of GFR Sympathetic division Strong stimulus = GFR Constriction of renal arterioles Slower flow Parasympathetic division Stimulus =? 46

47 Tubular Processing of Filtrate Reabsorption & secretion processes Reclaim desired filtrate components Discard additional/excess plasma components Structures involved Proximal tubule Loop of Henle Distal tubule Collecting ducts 47

48 Typical F, R & E Rates Tab

49 Transport Mechanisms Paracellular and transcellular pathways Active & passive processes Benefits of active transport? Primary & secondary active transport cotransport Pumps, channels or endocytosis Figs. 27-1, 3 49

50 Na + H 2 O Transport Mechanisms Reabsorbed primarily by transcellular active transport Reabsorbed entirely by osmosis (passive) 50

51 Rate of transport dependent on limitations of transport mechanisms Transport maximum Active Transport Rate Point at which transport mechanisms are saturated Solutes in concentration above this point will be excreted Substance glucose amino acids plasma proteins creatinine* See p.331 Transport Maximum 320 mg/min 1.5mM/min 30 mg/min 16 mg/min 51

52 Glucose Transport Fig

53 Proximal Tubule Primary site of reabsorption Nearly all nutrients & other substances reabsorbed E.g., glucose, aa s, vitamins, electrolytes Substance % Reabsorbed in PT K + > 90 HCO - 3 ~ 90 Na + ~ 70 H 2 O ~ 70 Cl - ~ 50 53

54 Extensive brush border Proximal Tubule Increased surface area for transport E.g., glucose, aa s, vitamins, electrolytes Fig

55 Loop of Henle Descending limb Thin segment Very permeable to H 2 O Reabsorption Concentrates filtrate Ascending limb Thick segment Impermeable to H 2 O Active reabsorption Na +, K +, Cl - Dilutes filtrate Fig

56 Ascending Loop Thick Segment Fig

57 Distal Tubule Additional reabsorption dependent on body needs Only ~10% Na + & ~20% H 2 O from original filtrate remaining Na + reabsorption enhanced by aldosterone Site of atrial naturietic peptide activity Na + reabsorption blood vol. & pressure Fig

58 Reabsorption of H 2 O ADH Collecting Duct Reabsorption of urea Acid (H + ) & base (HCO 3- ) regulation Fig

59 Solute Concentrations Through the Tubular System Secreted (not needed) Reabsorbed (needed) Fig

60 ~ 95% H 2 O ~ 5% solutes urea Na + K + Urine Composition phosphates uric acid creatinine Normal osmolarity ~500 mosm/l 60

61 Diuresis Fig

62 Urine Formation Kidneys can regulate water excretion independent of solute excretion. Therefore Can excrete large volumes of dilute urine Can excrete small volumes of concentrated urine Can do both without major changes in rates of solute excretion 62

63 Dependent on Nephron structure Concentrating Urine Hyperosmotic interstitial concentration gradient of the medulla 63

64 Formation of Dilute Urine Purpose: excretion of excess water Primary influence = ADH plasma osmolarity ADH secretion H 2 O reabsorption [urine] / output Fig

65 ADH [electrolytes] osmosis H 2 O Y cell swells Y signal post. pituitary [electrolytes] H 2 O not reabsorbed X kidneys ADH 65

66 Tubular activity Formation of Dilute Urine Cortical nephrons Low [ADH] Fig Max Output: ~ 50 mosm/l 66

67 Formation of Concentrated Urine Purpose: water conservation ADH influence plasma osmolarity ADH secretion H 2 O reabsorption [urine] / output Influence of the hyperosmotic environment of renal medulla

68 ADH [electrolytes] osmosis H 2 O Y cell shrinkage Y signal posterior pituitary ADH [electrolytes] reabsorb H 2 O kidneys 68

69 Formation of Concentrated Urine Tubular activity Juxtamedullary nephrons High [ADH] Fig

70 Formation of Concentrated Urine Maximum concentrating ability of kidney dictates how much urine volume must be excreted daily to rid body of metabolic wastes Normal human (70 kg) Need to excrete ~600 mosm/day Max. concentrating ability ~1200 mosm/l Obligatory (minimal) urine volume 600 / 1200 = 0.5 L/day 70

71 Formation of Concentrated Urine Urine concentrating abilities of mammals Human ~1200 mosm/l Aquatic mammals (beaver) ~500 mosm/l Desert mammals (kangaroo rat) ~10,000 mosm/l 71

72 Sea water So You re Adrift at Sea ~3% salt (~ mosm/l) Human drinking 1 L of sea water Solute intake of 2400 mosm Max. concentrating ability 1200 mosm 2400 / 1200 = 2 L urine output Kangaroo Rat drinking sea water 2400 / 10,000 =.24 L urine output 72

73 Countercurrent Mechanism Generates & maintains hyperosmotic environment of medulla Countercurrent multiplier system Establishes hyperosmotic state Loop of Henle & collecting ducts Countercurrent exchange system Maintains hyperosmotic state Vasa recta See Fig

74 Countercurrent Multiplier System Major factors contributing to solute buildup in medulla Active transport of Na +, K +, Cl - & other ions out of the loop of Henle (ascending limb) Active transport of ions from collecting ducts Diffusion of urea from collecting ducts Diffusion of only small amounts of water relative to reabsorption of other solutes 74

75 Countercurrent Multiplier System Assume all concentrations equal (starting point) Active transport of ions in ascending limb Osmosis of H 2 O out of descending limb Additional fluid flow through loop Fig

76 Countercurrent Multiplier System With time & continued concentration of filtrate Active pumping of ions multiplies interstitial solute concentrate Net effect Solutes added to medullary interstitium in excess of water 76

77 Countercurrent Multiplier System Impact of urea Concentrates in distal tubule & superior collecting duct (impermeable) Inferior collecting duct permeable Urea diffuses into medulla Further increases concentration gradient Recirculation into descending loop helps trap urea in medulla Fig

78 Countercurrent Exchange System Major factor in the preservation / maintenance of the medullary solute concentration Involves vasa recta Special characteristics Low blood flow U-shape High permeability to H 2 O, Na + & Cl - along entire length Fig Supplies metabolic needs of medullary tissues but minimizes solute loss 78

79 Renal Clearance The volume of plasma completely cleared of a substance per unit time Use to quantify kidney function 79

80 Clearance rate (ml/min) Renal Clearance C s = (U s x V) / P s U s = [urine]of substance, V = urine flow rate, P S = [plasma] of substance Use to Estimate GFR Conditions for accurate determination Freely filterable Not reabsorbed or secreted GFR = C s 80

81 Example: inulin Administered IV Renal Clearance C s = (U s x V) / P s C s = (125 mg/ml x 1 ml/min) 1 mg/ml Fig C s = GFR = 125 ml/min 81

82 Renal Clearance Compare other solutes to inulin C s = inulin Filtered, not reabsorbed or secreted C s < inulin Filtered & reabsorbed C s > inulin Filtered & secreted Substance C s (ml/min) Glucose 0.0 Na+ 0.9 Cl- 1.3 K PO Inulin Creatinine See p

83 Kidney Failure & Hemodialysis Loss of kidney function Infection, trauma, toxin poisoning, inadequate blood flow Hemodialysis Use semipermeable membrane to facilitate solute transfer between patient blood and dialyzing fluid 83

84 Dialyzing Fluid Tab

85 Artificial Kidney Fig