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Volume of Urine

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

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  1. Volume of Urine GFR ~ 50 - 200 L/d Urine, ~ 0.5 – 15 L/d

  2. 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

  3. 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

  4. Effect of Changing NaCl in Diet Weight Kg 10 Na+ intake NaCl gr 5.0 UNa+ • V Days

  5. Renal Architecture Na filtered = GFR x PNa Na excreted = V x UNa

  6. Nephron Segments

  7. Fractional Na+in Urine along the Nephron Fraction in urine (x 100)

  8. % Reabsorption of Filtered NaCl

  9. Renal Oxygen Consumption

  10. 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

  11. 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

  12. Tubular Segments PCT DCT CD ThAL

  13. Proximal Tubule Na+ Reabsorption Na Glucose, AA Na Na H+ H2O K HCO3 Na Na/H exchanger Na/solute co-transporter

  14. Starling’sForces in Peritubular Capillary PR = Kf (C - i) – (PC- Pi) PR = Kf ( - P)

  15. 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 )

  16. 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

  17. Apical Transporters of the Thick Ascending Limb NKCC ROMK Nielsen et al., Amer. J. Physiol. 282: F34.2002

  18. Sodium Absorption in Distal Tubule Na TSC K TSC Na:Cl Co-transporter Thiazide sensitive cotransporter

  19. Sodium Absorption in Collecting Duct Na ENaC K K ENaC Epithelial Na Channel Amiloride sensitive K K channel

  20. Aldosterone Effect on Na+ and K+ in the Collecting Duct Aldo

  21. Renin-Angiotensin System aldosterone; CD reabsorption angiotensinogen renin angiotensin I converting enzyme angiotensin II efferent constriction; PT reabsorption vasoconstriction

  22. Effect of Changing NaCl in Diet Weight Kg 10 Na+ intake NaCl gr 5.0 UNa+ • V Days

  23. Renal Handling of Glucose

  24. 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

  25. Plasma ADH (AVP)

  26. Urine Osmolality as a function of Plasma ADH

  27. Urine/Plasma Osmolality in Rat Posmol 290 mosm/Kg H20 Uosmol max: 1200 min: 60mosm/Kg H20

  28. 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

  29. 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

  30. Cell Types of the Collecting Tubule PrincipalNa + absorptionENaC Water absorptionAquaporin 2 K + secretion ROMK IntercalatedH+ TransportH + ATPase

  31. 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

  32. 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

  33. Urine/Plasma Osmolality in Rat Posmol 290 mosm/Kg H20 Uosmol max: 1200 min: 60mosm/Kg H20

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