1. Water Balance: Hypo- and Hypernatremia Vivek Bhalla, MD Division of Nephrology Stanford University School of Medicine September 14th, 2015

2. Clinical Relevance

3. Learning Objectives (5) Define serum osmolality Review ADH release and action on the kidney Define Hyponatremia and discuss causes Define Hypernatremia and discuss causes Distinguish between disorders of water and salt

4. Serum Osmolality Posm = 2Na + Glucose/18 + BUN/2.8

5. Serum Osmolality Posm = 2Na + Glucose/18 + BUN/2.8 Effective Posm = 2Na

6. Serum Osmolality Posm = 2Na + Glucose/18 + BUN/2.8 Effective Posm = 2Na Na concentration [Na] = Na / H2O

7. Serum Osmolality Posm = 2Na + Glucose/18 + BUN/2.8 Effective Posm = 2Na Na concentration [Na] = Na / H2O If Sodium amount changes or H2O water changes then [Na] changes

8. Osmolality is a force… CellBlood Vessel

9. 280 CellBlood Vessel Serum Osmolality

10. 280 260 280 Serum Osmolality

11. 280 260 Serum Osmolality

12. 280 260 320 280

13. 260 320

14. Osmotic sensors in the Hypothalamus (H) ADHRelease

15. Hypothalamus Paraventricular NeuronsParaventricular Neurons Supraoptic NucleiSupraoptic Nuclei

16. ADH Release

17. ADH Action Low ADH 200 Low Uosm = 100-200 mOsm

18. 280 H ADHRelease

19. 310 ADHRelease H

20. ADHRelease H

21. ADH Action High ADH 400 600 800 1000 1200 High Uosm = 1000-1200 mOsm

22. ADH Release

23. 280 H ADHRelease

24. H ADHRelease

25. ADH Action High ADH 400 600 800 1000 1200 High Uosm = 1000-1200 mOsm

26. Hyponatremia Defined as a plasma sodium concentration of < 135 mEq/L Implies hypo-osomolality Na/ECF (water)

27. ADH Release

28. Heart failure Cirrhosis Nephrotic syndrome Volume depletion Decreased effective arterial blood volume “Appropriate” ADH release H ADHRelease

29. Heart failure Cirrhosis Nephrotic syndrome Volume depletion Normal effective arterial blood volume SIADH H * ADHRelease

30. Hyponatremia SIADH Tumors (brain/lung) Medications Heart Failure Cirrhosis Nephrotic syndrome Volume depletion *

31. Diuretics and Water Balance Do thiazide diuretics predispose to hyponatremia? Do loop diuretics predispose to hyponatremia?

32. ADH Action High ADH 400 600 800 1000 1200 High Uosm = 100 mOsm

33. Diuretics and Water Balance Do thiazide diuretics predispose to hyponatremia? –Sodium reabsorbed in distal convoluted tubule with no concomitant water reabsorption –ADH can be increased if patient has volume depletion due to diuretics Do loop diuretics predispose to hyponatremia? –Sodium reabsorbed in thick limb of loop of Henle with no concomitant water reabsorption, but…. –ADH can’t work because NKCC2 required for generation and maintenace of hyperosmotic medulla, i.e. nothing for ADH to act on Yes No

34. Hypernatremia Na concentration [Na] = Na/H2ONa concentration [Na] = Na/H2O

35. Hypernatremia No access to water Kidney losing water

36. 280 310 H ADHRelease

37. H ADHRelease

38. ADH Release

39. What if the kidney is losing water?

40. No effective ADH Action Low ADH 200 Low Uosm = 100-200 mOsm

41. Case 47 year old Asian female with past history of breast CA Admitted to the hospital with pneumonia Required mechanical ventilation Her plasma osmolality began rising –P osm of 280 on admission –Increased to 290, then 300, then 310

42. Case Despite the rise in her Posm, her urine output was excessive and dilute The urine osm was only 100 mOsm/L

44. What if the kidney is losing water? Diabetes insipidus –Central Tumor that disrupts ADH release Ischemia (e.g. Sheehan’s syndrome)

45. Case 52 y/o male with a past psychiatric history presents with an acute gallbladder attack and is taken to the operating room. His serum sodium is 145 meq/L preoperatively and rises to 160 meq/L by the next morning. The nurses note a large urine output.

46. Case Serum sodium = 160 meq/L Urine osm = 140 mOsm/kg The physicians administer subcutaneous vasopressin (ADH) and there is no change in the Urine osm. Diagnosis?

47. Na Principal Cell of the Distal Nephron AQP2

48. Li Principal Cell of the Distal Nephron AQP2

50. Li Principal Cell of the Distal Nephron

51. What if the kidney is losing water? Diabetes insipidus –Central Tumor that disrupts ADH release Ischemia Alcohol –Nephrogenic Lithium

52. The Difference between Salt and Water Salt : Disorders of Volume –e.g. salt-sensitive hypertension (too much salt and water; but isotonic) Salt concentration: Disorders of Water –e.g. hyponatremia (too much water RELATIVE to salt) A patient can have one, the other, or both

53. The Difference between Salt and Water NORMAL HYPONATREMIA Na HYPONATREMIA Na HYPONATREMIA Na HYPOVOLEMIA EUVOLEMIAHYPERVOLEMIA

54. The Difference between Salt and Water NORMAL HYPERNATREMIA Na HYPERNATREMIA Na HYPERNATREMIA Na HYPOVOLEMIA EUVOLEMIAHYPERVOLEMIA Na

55. Learning Objectives (5) Define serum osmolality Review ADH release and action on the kidney Define Hyponatremia and discuss causes Define Hypernatremia and discuss causes Distinguish between disorders of water and salt