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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 “ H 2 0 ~ 0.5-3 L/day H + ~ 50-100 mEq/day. Air water ~ 3000 mOsm/Kg H 2 0. Extracellular Fluid Volume ~ 1/3 body water ; Osmol 290 mOsm/Kg H 2 0
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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 bodywater; 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
Effect of Changing NaCl in Diet Weight Kg 10 Na+ intake NaCl gr 5.0 UNa+ • V Days
Renal Architecture Na filtered = GFR x PNa Na excreted = V x UNa
Fractional Na+in Urine along the Nephron Fraction in urine (x 100)
Na K Sodium Absorption 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 CD ThAL
Proximal Tubule Na+ Reabsorption Na Glucose, AA Na Na H+ H2O K HCO3 Na Na/H exchanger Na/solute co-transporter
Starling’sForces in Peritubular Capillary PR = Kf (C - i) – (PC- Pi) PR = Kf ( - P)
Driving Forces for Salt and WaterAbsorption in the Proximal Tubule Lumen Capillary Trans-cellular 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-KbChloride Channel
Apical Transporters of the Thick Ascending Limb NKCC ROMK Nielsen et al., Amer. J. Physiol. 282: F34.2002
Sodium Absorption in Distal Tubule Na TSC K TSC Na:Cl Co-transporter Thiazide sensitive cotransporter
Sodium Absorption in Collecting Duct Na ENaC K K ENaC Epithelial Na Channel Amiloride sensitive K K channel
Aldosterone Effect on Na+ and K+ in the Collecting Duct Aldo
Renin-Angiotensin System aldosterone; CD reabsorption angiotensinogen renin angiotensin I converting enzyme angiotensin II efferent constriction; PT reabsorption vasoconstriction
Effect of Changing NaCl in Diet Weight Kg 10 Na+ intake NaCl gr 5.0 UNa+ • V Days
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
Urine/Plasma Osmolality in Rat Posmol 290 mosm/Kg H20 Uosmol max: 1200 min: 60mosm/Kg H20
Tubular Fluid Osmolality PCT DCT CD ThAL 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
AQP2 V2R Mechanism of action of Vasopressin 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 PrincipalNa + absorptionENaC Water absorptionAquaporin 2 K + secretion ROMK IntercalatedH+ TransportH + ATPase
Urinary Concentration NaCl NaCl H2O H2O NaCl Cortical collecting duct H2O 100 60 150 Descending limb NaCl Distal tubule 300 300 NaClK H2O 300 100 +ADH 600 Ascending limb H2O NaClK 600 400 H2O Urea Medullary collecting duct NaClK 900 900 900 700 H2O H2O NaCl NaClK 1000 Urea 1200 1000 1000 H2O H2O Urea 1200 1200 1200 H2O Active transport Passive Cortex Medulla
Urinary Concentration and Dilution 1400 % water remaining 25% 1200 < 1% 900 Osmolarity (mOsm/L) 600 Maximal ADH 300 3% 35% 15% 10% No ADH Proximal tubule Henle’s loop Distal tubule Cortical collecting duct Medullary collecting duct
Urine/Plasma Osmolality in Rat Posmol 290 mosm/Kg H20 Uosmol max: 1200 min: 60mosm/Kg H20