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

2. Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) 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 urine

3. 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 How do we maintain ECF Volume?

5. Weight NaCl gr 10 5.0 Days Na + intake U Na + V Kg Effect of Changing NaCl in Diet

6. Renal Architecture Na filtered = GFR x P Na Na excreted = V x U Na

7. Nephron Segments

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

9. % Reabsorption of Filtered NaCl

10. Renal Oxygen Consumption

11. 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 Sodium Absorption

12. 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 The Na + K + ATPase

13. PCT DCT ThAL CD Tubular Segments

14. Na K Glucose, AA Na H+ H 2 O Proximal Tubule Na + Reabsorption HCO 3 Na Na/H exchanger Na/solute co-transporter

15. P R = Kf (  C -  i ) – (P C - P i ) P R = Kf (  -  P) Starling’s Forces in Peritubular Capillary

16. Lumen Capillary Trans-cellular Active transport of Na and HCO 3 Intercellular Leak Starling Forces across capillary (  P  Driving Forces for Salt and Water Absorption in the Proximal Tubule

17. Na K NKCC ROMK NKCCNa:K:2Cl Co-transporter Furosemide sensitive cotransporter ROMKK channel CLC-KbChloride Channel CLC-Kb Sodium Absorption in Thick Ascending Limb

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

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

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

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

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

23. Weight NaCl gr 10 5.0 Days Na + intake U Na + V Kg Effect of Changing NaCl in Diet

24. Renal Handling of Glucose

25. Cells Extracellular Fluid Volume ~ 1/3 body water; Osmol 290 mOsm/Kg H 2 0 Na + 142 mM; K + 4 mM; H + 40 nM (pH 7.40) 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 urine

27. Plasma ADH (AVP)

28. Urine Osmolality as a function of Plasma ADH

29. Urine/Plasma Osmolality in Rat Posmol 290 mosm/Kg H 2 0 Uosmol max: 1200 min: 60 mosm/Kg H 2 0

30. 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 Tubular Fluid Osmolality

31. Binds to V2 Receptor in collecting tubule Increases production of cyclic AMP Causes fusion of vesicles containing Aquaporin 2 with the apical membrane AQP2 V2R Mechanism of action of Vasopressin

32. PrincipalNa + absorption ENaC Water absorptionAquaporin 2 K + secretionROMK IntercalatedH + TransportH + ATPase Cell Types of the Collecting Tubule

33. Descendinglimb 300 600 900 1200 H2OH2OH2OH2O H2OH2OH2OH2O H2OH2OH2OH2O 1200 1000 700 NaClK 400 100 NaClK NaClK NaClK 100 H2OH2OH2OH2ONaCl H2OH2OH2OH2ONaCl 60150 NaCl H2OH2OH2OH2O NaCl Corticalcollectingduct Distal tubule Ascendinglimb Urea 300 H2OH2OH2OH2O 600 H2OH2OH2OH2O Urea 900 H2OH2OH2OH2O NaCl 1000 H2OH2OH2OH2O Urea 1200 H2OH2OH2OH2O 300 900 1000 1200 Medullarycollectingduct +ADH Active transport Passive Urinary Concentration Cortex Medulla

34. 300 600 900 1200 1400 35% 25% 15% 3% < 1% 10% No ADH MaximalADH ProximaltubuleHenle’sloopDistaltubuleCorticalcollectingductMedullarycollectingduct Osmolarity (mOsm/L) Urinary Concentration and Dilution % water remaining

35. Urine/Plasma Osmolality in Rat Posmol 290 mosm/Kg H 2 0 Uosmol max: 1200 min: 60 mosm/Kg H 2 0