1. Daniel R. Kapusta, Ph.D. Department of Pharmacology, LSUHSC MEB Rm 7106 568-3940; dkapus@lsuhsc.edu Urine Concentration and Dilution Regulation of Sodium and Water Balance

2. Urine Concentration and Dilution

3. AVP-dependent water permeability in the distal nephron

4. Aquaporin 2 – mediated water reabsorption in DCT

5. Countercurrent SYSTEM 1. Countercurrent flow: direction – anatomy 2. Countercurrent exchange: vasa recta 3. Countercurrent multiplication: tubules

6. 1. Countercurrent FLOW  DVR  TAL  tdloop  AVR * Hairpin configuration - anatomical - loops of Henle (tubules) - vasa recta (capillaries) * Descending limbs close to ascending limbs * Fluid flow in opposite directions

7. 2. Countercurrent EXCHANGER * Vasa recta (capillaries) - Countercurrent exchangers - Passive process depends on diffusion of solutes & water in both directions across permeable walls of the vasa recta

8. 3. Countercurrent MULTIPLIER Loops of Henle (tubules) * countercurrent multipliers - Pumping solute creates a large axial gradient - Establishes hyperosmotic medullary interstitial fluid ISF Osmotic gradient

9. Segmental renal tubular sodium reabsorption

10. Recycling of urea in the kidney

11. Renal handling of water in states of water diuresis

12. Renal handling of water in states of antidiuresis

13. Renal handling of water in states of water diuresis and antidiuresis

14. SIADH – Syndrome of inappropriate secretion of ADH Central diabetes insipidus Nephrogenic diabetes insipidus Vasopressin Pathologies

15. Regulation of Sodium and Water Balance

16. Distribution of Total Body Water (TBW)

17. Total Body Water Balance: Input = Output

18. Total Body Sodium Balance: Input = Output

19. Regulation of Arterial Blood Pressure BP = CO x TPR

20. Regulation of Arterial Blood Pressure BP = CO x TPR HR x SV

21. Regulation of Arterial Blood Pressure

22. Volume and Sodium/Osmole Sensors

24. Regulation of Arterial Blood Pressure: Closed loop system

25. Regulation of Arterial Blood Pressure and Total Body Water / Sodium Balance Neural Control

26. Neural Control Mechanisms: Baroreceptors

27. Sympathetic control mechanisms regulating arterial blood pressure and sodium/water excretion

28. Renal sympathetic nerves and kidney function

29. Renal nerves contribute to segmental renal tubular sodium reabsorption

30. Renal nerves innervate the afferent renal arterioles:  1 receptor activation: renin release  1 adrenoceptor activation: vasoconstriction

31. Reduction in arterial blood volume activates the renal sympathetic nerves to enhance renal tubular sodium reabsorption

32. Regulation of Arterial Blood Pressure and Total Body Water / Sodium Balance Humoral Control - Angiotensin II - Aldosterone - Atrial Natriuretic Peptide (ANP)

33. The renin-angiotensin-aldosterone system

34. Angiotensin II

35. Regulation of extracellular fluid volume

36. Angiotensin II and renovascular hypertension

37. Angiotensin and aldosterone enhance the renal tubular reabsorption of sodium  U Na V

38. Chronic high salt diet reduces plasma renin (and Ang II) and increases plasma atrial natriuretic peptide levels High NaCl intake

39. Volume expansion: Integration of neural and humoral pathways to augment sodium and water excretion

40. Volume contraction: Integration of neural and humoral pathways to reduce sodium and water excretion

41. Deranged neural and humoral control in hypertension

42. Deranged neural and humoral control in congestive heart failure

43. Regulation of Arterial Blood Pressure and Total Body Water / Sodium Balance Humoral Control AVP = ADH

44. Hypothalamic control of vasopressin (antidiuretic hormone) secretion

45. ADH secretion is more sensitive to changes in plasma osmolarity than to changes in blood volume

46. At plasma AVP levels that evoke thirst, water reabsorption and urine osmolality are already maximally increased

47. Central “osmoreceptors” and AVP secretion

48. Major Causes of Hyponatremia and Hypo-osmolality

49. Major Causes of Hypernatremia