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Download Renin-Angiotensin System
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Volume of Urine GFR ~ 50 200 L/d Urine, ~ 0.5 – 15 L/d Intake: Na+ ~ 5-200 mmoles/day K+~ 50-300 “ H20 ~ 0.5-3 L/day H+ ~ 50-100 mEq/day Air water ~ 3000 mOsm/Kg H20 Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H20 Na+ 142 mM; K+ 4 mM; H+ 40 nM (pH 7.40) Cells urine How do we maintain ECF Volume? By keeping ECV Na+ content, ECFV (~ 10-15 L) x [Na+] (140 mEq/L) ~ 1,400 – 2,100 mEq fairly constant despite variations on intake Na+ EC 288 Na+ Cl- mOsm/kg Thirst H2O intake ADH H2O excretion Osmol IC Na+ H2 O EC Na+ Cl- 288 mOsm/kg Thirst Osmol ADH IC H2 O H2O excretion Effect of Changing NaCl in Diet Weight Kg 10 Na+ intake NaCl 5.0 gr UNa+ • V Days Renal Architecture Na filtered = GFR x PNa Na excreted = V x UNa Nephron Segments Fractional Na+in Urine along the Nephron Fraction in urine (x 100) % Reabsorption of Filtered NaCl Renal Oxygen Consumption Sodium Absorption Na K Entry into the Cell down an electrochemical gradient Na channel, or Na coupled solute carriers Exit into the blood by the Na:K ATPase The Na + K + ATPase Located in the basolateral membrane of Renal Tubular Cells Inhibited by the cardiac glycosides digoxin and ouabain Nielsen et al., Amer. J. Physiol.277:F257. 1999 Tubular Segments PCT DCT ThAL CD Proximal Tubule Na+ Reabsorption Glucose, AA Na K HCO3 Na Na/H exchanger Na/solute co-transporter Na Na H+ H O 2 Starling’s Forces in Peritubular Capillary PR = Kf (C - i) – (PC- Pi) PR = Kf ( - P) Driving Forces for Salt and Water Absorption in the Proximal Tubule Capillary Trans-cellular Lumen Active transport of Na and HCO3 Intercellular Leak Starling Forces across capillary (DP - DP ) Sodium Absorption in Thick Ascending Limb Na CLC-Kb NKCC K ROMK NKCC Na:K:2Cl Co-transporter Furosemide sensitive cotransporter ROMK K channel CLC-Kb Chloride Channel Apical Transporters of the Thick Ascending Limb NKCC Nielsen et al., Amer. J. Physiol. 282: F34.2002 ROMK Sodium Absorption in Distal Tubule TSC Na K TSC Na:Cl Co-transporter Thiazide sensitive cotransporter Sodium Absorption in Collecting Duct Na K ENaC K ENaC K Epithelial Na Channel Amiloride sensitive K channel Aldosterone Effect on Na+ and K+ in the Collecting Duct Aldo Renin-Angiotensin System angiotensinogen renin angiotensin I converting enzyme angiotensin II efferent constriction; PT reabsorption vasoconstriction aldosterone; CD reabsorption Effect of Changing NaCl in Diet Weight Kg 10 Na+ intake NaCl 5.0 gr UNa+ • V Days Renal Handling of Glucose Intake: Na+ ~ 5-200 mmoles/day K+~ 50-300 “ H20 ~ 0.5-3 L/day H+ ~ 50-100 mEq/day Air water ~ 3000 mOsm/Kg H20 Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H20 Na+ 142 mM; K+ 4 mM; H+ 40 nM (pH 7.40) Cells urine Na+ EC 288 Na+ Cl- mOsm/kg Thirst H2O intake ADH H2O excretion Osmol IC Na+ H2 O EC Na+ Cl- 288 mOsm/kg Thirst Osmol ADH IC H2 O H2O excretion Plasma ADH (AVP) Urine Osmolality as a function of Plasma ADH Urine/Plasma Osmolality in Rat Posmol 290 mosm/Kg H20 Uosmol max: 1200 min: 60 mosm/Kg H20 Tubular Fluid Osmolality PCT DCT ThAL CD PCT iso-osmolar ThAL hypo-osmolar DCT hypo-osmolar CD hypo-osmolar in the absence of vasopressin (Antidiuretic Hormone) hyper-osmolar in the presence of vasopressin Mechanism of action of Vasopressin AQP2 V2R Binds to V2 Receptor in collecting tubule Increases production of cyclic AMP Causes fusion of vesicles containing Aquaporin 2 with the apical membrane Cell Types of the Collecting Tubule Na + absorption Water absorption K + secretion Intercalated H+ Transport Principal ENaC Aquaporin 2 ROMK H + ATPase Urinary Concentration Active transport Passive NaCl NaCl H2O H2O NaCl 100 Descending limb 60 H2O 150 NaCl Cortical collecting duct Distal tubule Cortex 300 NaClK Medulla600 NaClK H2O 100 300 400 Ascending limb H2O H2O H2O 700 900 NaClK 1000 Urea 1200 H O 1000 2 1200 +ADH 600 Urea NaClK 900 300 900 H2O NaCl H2O 1000 Urea 1200 H2O 1200 Medullary collecting duct Urinary Concentration and Dilution Osmolarity (mOsm/L) 1400 25% % water remaining 1200 < 1% 900 600 Maximal ADH 300 3% 35% Proximal tubule 15% Henle’s loop No ADH Distal tubule Cortical collecting duct 10% Medullary collecting duct Urine/Plasma Osmolality in Rat Posmol 290 mosm/Kg H20 Uosmol max: 1200 min: 60 mosm/Kg H20
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