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Tublar transport & Osmolality.ppt
- 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 H20 Na+ 142 mM; K+ 4 mM; H+ 40 nM (pH 7.40) 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 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?
- 4. IC EC Na+ Cl- 288 mOsm/kg Osmol Thirst ADH H2O intake H2O excretion EC Na+ Cl- 288 mOsm/kg Osmol Thirst ADH H2O excretion H2O H2O Na+ Na+ IC
- 5. Weight NaCl gr 10 5.0 Days Na+ intake UNa + • V Kg Effect of Changing NaCl in Diet
- 6. Renal Architecture Na filtered = GFR x PNa Na excreted = V x UNa
- 8. Fraction in urine (x 100) Fractional Na+in Urine along the Nephron
- 9. % Reabsorption of Filtered NaCl
- 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 Na H+ H 2 O Proximal Tubule Na+ Reabsorption HCO3 Na Na/H exchanger Na/solute co-transporter
- 15. PR = Kf (C - i) – (PC- Pi) PR = Kf ( - P) Starling’s Forces in Peritubular Capillary
- 16. Lumen Capillary Trans-cellular Active transport of Na and HCO3 Intercellular Leak Starling Forces across capillary (DP - DP ) Driving Forces for Salt and Water Absorption in the Proximal Tubule
- 17. Na K NKCC ROMK NKCC Na:K:2Cl Co-transporter Furosemide sensitive cotransporter ROMK K channel CLC-Kb Chloride 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 K K 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 UNa + • 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 H20 Na+ 142 mM; K+ 4 mM; H+ 40 nM (pH 7.40) 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 urine
- 26. IC EC Na+ Cl- 288 mOsm/kg Osmol Thirst ADH H2O intake H2O excretion EC Na+ Cl- 288 mOsm/kg Osmol Thirst ADH H2O excretion H2O H2O Na+ Na+ IC
- 27. Plasma ADH (AVP)
- 28. Urine Osmolality as a function of Plasma ADH
- 29. Urine/Plasma Osmolality in Rat Posmol 290 mosm/Kg H20 Uosmol max: 1200 min: 60 mosm/Kg H20
- 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. Principal Na + absorption ENaC Water absorption Aquaporin 2 K + secretion ROMK Intercalated H+ Transport H + ATPase Cell Types of the Collecting Tubule
- 33. Descending limb 300 600 900 1200 H2O H2O H2O 1200 1000 700 NaClK 400 100 NaClK NaClK NaClK 100 H2O NaCl H2O NaCl 60 150 NaCl H2O NaCl Cortical collecting duct Distal tubule Ascending limb Urea 300 H2O 600 H2O Urea 900 H2O NaCl 1000 H2O Urea 1200 H2O 300 900 1000 1200 Medullary collecting duct +ADH Active transport Passive Urinary Concentration Cortex Medulla
- 34. 300 600 900 1200 1400 35% 25% 15% 3% < 1% 10% No ADH Maximal ADH Proximal tubule Henle’s loop Distal tubule Cortical collecting duct Medullary collecting duct Osmolarity (mOsm/L) Urinary Concentration and Dilution % water remaining
- 35. Urine/Plasma Osmolality in Rat Posmol 290 mosm/Kg H20 Uosmol max: 1200 min: 60 mosm/Kg H20