1. Vivek Bhalla, MD Division of Nephrology Stanford University School of Medicine September 14th, 2015 Regulation of Water Balance

2. Learning Objectives (3) 1.A rise in tonicity does what? –Stimulates ADH, thirst 2. How is the kidney primed to concentrate urine? –Countercurrent multiplication –Countercurrent exchange 3. How that concentrating mechanism is utilized to maintain water balance? –What does ADH do to the kidney?

3. “Big Picture” Hypothalamus

4. “Big Picture” Hypothalamus

5. Hypothalamus Paraventricular NeuronsParaventricular Neurons Supraoptic NucleiSupraoptic Nuclei

6. ADH Release

7. Kidney Anatomy

8. Hyperosmotic Medulla Tubular LumenTubular Lumen Tubular epithelial CellsTubular epithelial Cells InterstitiumInterstitium Endothelial cells – vasa rectaEndothelial cells – vasa recta Blood within the vasa rectaBlood within the vasa recta

9. Kidney Anatomy Tubular LumenTubular Lumen Tubular epithelial CellsTubular epithelial Cells InterstitiumInterstitium Endothelial cells – vasa rectaEndothelial cells – vasa recta Blood within the vasa rectaBlood within the vasa recta

10. Kidney Anatomy

11. Hyperosmotic Medulla How is this gradient established?

12. Hyperosmotic Medulla

13. Counter Current Multiplication

15. Countercurrent Multiplication

16. Countercurrent Exchange A-Artery B-Vein C-Collecting Duct

17. Countercurrent Exchange

18. Too Much or Too Little ADH % of water remaining In the lumen Relative to the original glomerular filtrate

19. Aquaporins – Water Channels

21. Urinary Concentration

22. Take Home Points (3) 1.ADH release and thirst are regulated by tonicity 2. Countercurrent multiplication and exchange ready the medulla for ADH-dependent water reabsorption 3. ADH stimulates Aquaporin 2 insertion in the luminal (apical) membrane along the collecting duct