1. WATER AND ELECTROLYTE BALANCE DRANITZKI ELHALEL MICHAL, MD NEPHROLOGY AND HYPERTENSION SERVICES

2. Total Body Water (TBW) Intracellular space Interstitium } extracellular Vascular Space }

3. TBW = 60% of Body Weight 60% of TBW (36% of weight) - intracellular 40% of TBW (24% of weight) - extracellular

4. Exchange of water between cellular and extracellular fluids 1. OSMOTIC PRESSURE - generated by number of particles per unit volume 2. HYDROSTATIC PRESSURE

5. Main intracellular osmole  K + Main extracellular osmole  Na + Extracellular osmolarity ~2xNa + Extracellular osmolarity = Intracellular osmolarity Normal osmolarity ~280 mOsmol/Kg ~140 mEq/L of Na +

6. 70 kg, male TBW - 42 liter Total Body Solute - 42 liter x 280 mOsmol/l = 11.760 mOsmol Intracellular volume - 25 liter Intracellular osmoles - 25 liter x 280 mOsmol/l = 7000 mOsmol Extracellular volume - 17 liter Extracellular osmoles - 17 liter x 280 mOsmol/l = 4760 mOsmol

7. Substance Plasma Plasma Extracellular Intracellular added osmolarity sodium volume volume NaCl     Water     Isotonic NaCl 0 0  0

8. Plasma Na + concentration is a measure of concentration and not of volume, or of total body sodium

9. Plasma osmolarity  2 x plasma [Na+] + Glucose + Urea ---------------------------------------- Normal values: P Na - 137 - 145 mEq/L Glucose - 3.5-6.5 mmol/L Urea - 3.5-6.5 mmol/L P osm - 275-290 mOsmol/kg Effective P osm - 270-285 mOsm/kg

10. Exchange of Water between Plasma and Interstitial Fluid - Oncotic pressure - Hydrostatic pressure

11. EFFECTIVE BLOOD VOLUME (EBV) 1.Volume in arterial system 2.Pressure perfusing the arterial baroreceptors (carotid, glomerular) REGULATION OF EFFECTIVE BLOOD VOLUME AFFECTS SODIUM STORES BY AFFECTING URINARY SODIUM EXCRETION

12. REGULATION OF EBV 1. SENSORS - volume/pressure receptors: - afferent arteriole - cardiopulmonary - atria - carotid

13. REGULATION OF EBV 2. EFFECTORS a. Sympathetic nervous system: - sympathetic nervous tone - secretion of catecholamines from adrenal medulla  Venous constriction Myocardial contractibility and heart rate Arteriolar constriction Renin secretion Renal tubular Na + reabsorption

14. REGULATION OF EBV b. Renin - Angiotensin - Aldosterone system: arteriolar vasoconstriction renal Na + retention (Angiotensin II, aldosterone) c. Atrial Natriuretic Peptide (ANP) d. Regulation of renal Na + excretion: varies directly with effective blood volume controlled by - GFR - Tubular reabsorption of Na +

15. VOLUME REGULATION Reduced EBV Elevated EBV Sympathetic tone   Renin, Angiotensin, Aldosterone   ANP   Renal sodium excretion  

16. 60-70% 20-30% 5% 4%

17. OSMOREGULATION SENSING - Osmoreceptors in hypothalamus EFFECTORS - Thirst  Drinking - Antidiuretic Hormone (ADH)  water excretion

18. Water Balance Obligatory water output: Urine - 500 ml Skin - 500 ml Respiratory tract - 400 ml Stool - 200 ml

19. Obligatory Water Intake Drinking400 ml Water content of food850 ml Water pruduced by oxidation 350 ml

21. Excersice on a Hot Day A. Water loss  Osmolarity  B. Water + Sodium loss Volume  Osmolarity   Thirst  } water retention  ADH  Volume  Urinary sodium excretion  ADH water retention  Urine - Osmolarity  Na +, Cl - 

22. Half Isotonic Saline Infusion A. Osmolarity   ADH  B. Volume   Sodium excretion  ADH   Urine - Osmolarity  Na +, Cl - 

23. Isotonic Saline Infusion A. Osmolarity - no change B. Volume   Sodium excretion  ADH  Urine - Isosmotic urine

24. Congestive Heart Failure A. EBV   Urinary Sodium excretion  ADH   Total Body Sodium  (Edema) Total Body water  Plasma Osmolarity  Plasma Sodium  Urine Osmolarity  Urine Na +, Cl - 

25. Primary Renal Sodium Retention Total Body Sodium  Total Body Water 

26. Secretory Diarrheas = Isoosmotic Fluid containing Na + and K + as in the Plasma EBV - decreased P Osm - no change P Na - no change ADH - increased Renin + Aldosterone - increased ANP - decreased  Urinary Sodium Excretion - decreased Urine Osmolarity - increased

28. Hyponatremia and hypoosmolality = Impaired renal water excretion Hypernatremia and hyperosmolarity = Impaired thirst mechanism or no access to water

29. Hypoosmolarity and Hyponatremia - SYMPTOMS Nausea Malaise Headache Lethargy Seizures Coma Cause - Brain Edema

30. Hyponatremia – Etiology Disorders of impaired water excretion A. Effective blood volume depletion GI losses Renal losses: diuretics, hypoaldostronism, Na + -wasting nephropathy Skin losses: exercise, burns Edematous states: heart failure, hepatic cirrhosis, nephrotic syndrome, protein loosing enteropathy B. Diuretics: Thiazides, loop diuretics C. Renal failure

31. Hyponatremia – Etiology D. Non-hypovolemic states ofADH excess Syndrom of inappropriate ADH secretion Cortisol deficiency Hypothiroidism E. Decreased solute intake F. Cerebral salt wasting Disordders with normal water excretion A. Primary polydipsia B. Reset osmostat: pregnancy, psychosis, quadriplegia, malnutrition

32. Diuretics 1. Volume depletion 2. Inhibition of urinary dilution 3. K + depletion Most common - THIAZIDES

33. 60-70% 20-30% 5% 4%

34. Syndrome of Inappropriate ADH Secretion = Impaired water excretion 1. Hypoosmolarity and Hyponatremia 2. Increased urine osmolarity NO DECREASED EBV Na + EXCRETION IS NORMAL

35. SIADH - ETIOLOGY 1. Neuropsychiatric disorders 2. Drugs 3. Pulmonary disease 4. Post-operative 5. Severe nausea 6. Ectopic production 7. Exogenous administration of ADH

36. PSEUDOHYPONATREMIA Low plasma Na + with normal P osm A. Severe hyperlipidemia B. Severe hyperproteinemia Low plasma Na + with elevated P osm A. Hyperglicemia B. Administration of hypertonic Manitol

38. Hyponatremia - DIAGNOSIS 1. Patient history 2. Estimate Volume status 3. Plasma Osmolarity 4. Urine Osmolarity 5. Urine Na + concentration

39. Hyponatremia – Treatment 1. Estimate neurological symptoms 2. Estimate volume status 3. Decide – water restriction or sodium load or both 4. Correct slowly!!!! ~ ½ meq/l/h TREAMENT COMPLICATION: CENTRAL PONTINE MYELINOLYSIS

40. Estimation of Sodium deficit Na + deficit = 0.5 x weight (125-plasma Na + ) Example: 70kg female, plasma Na + 113meq/l Na + deficit = 35(125-113)=420 meq Time of correction: 12meq/l =24h 0.5meq/l/h Fluids: Hypertonic (3%) saline = 513meq/l 420 meq = 818 ml of hypertonic saline

41. If hypovolemia coexist: Treat with normal (0.9%) saline. First, Sodium will rise slowly in plasma.When hypovolemia will be corrected ADH levels will drop, and water excretion will correct plasma Na +.

42. Treatment of SIADH 1.Water restriction 2. Hypertonic saline or NaCl tablets 3. Loop diuretics 4. Demeclocycline

44. Hyperosmolarity and Hypernatremia - SYMPTOMS Lethergy Weakness Irritability Twitching Seizures Coma Cause - Brain Dehydration

45. Hypernatremia – Etiology w ater loss A. Insensible loss – Increased sweating, evaporation Burns Respiratory infection B. Renal loss – Central Diabetes Insipidus Nephrogenic Diabetes Insipidus Osmotic diuresis C. Gastrointestinal loss – Osmotic diarrhea D. Hypothalamic disoreders E. Water loss into cells – Seizures Rabdomyolysis

46. Hypernatremia – Etiology cont. Sodium retention A. Administration of hypertonic NaCl or NaHCO 3 B. Ingestion of sodium

47. Hypernatremia – DIAGNOSIS 1. Patient history 2. Estimate volume status 3. Plasma osmolarity 4. Urine volume 5. Urine osmolarity 6. Urine Na + concentration

48. DIABETES INSIPIDUS- CENTRAL-ETIOLOGY 1.Idiopathic – familial 2. Post surgery to hyopthalamus 3. Head trauma 4. Hypoxic or ischemic encephalopathy (shock, arrest, Sheehan’s syndrom) 5. Neoplastic 6. Histiocytosis X 7. Sarcoidosis 8. Anorexia nervosa 9. Cerebral aneurysm 10. Encephalitis or meningitis

49. DIABETES INSIPIDUS – NEPHROGENIC- ETIOLOGY 1.Decreased water permeability of the collecting tubule a. Congenital b. Hypercalcemia c. Hypokalemia d. Drugs (Lithium, Demeclocycline, Streptozocin) e. Sjogren’s syndrom f. Amyloidosis

50. Diabetes Insipidus – Nephrogenic Etiology – con. 2. Interference with countercurrent mechanism a. Osmotic diuresis b. Loop diuretics c. Renal failure d. Hypercalcemia e. Hypokalemia f. Sickle cell anemia 3. Increased periferal degradation of ADH a. Pregnancy 4. Unknown mechanism a. Isofamid b. Methoxyflurane

52. Hypernatremia – Treatment 1. Estimate neurological symptoms 2. Estimate volume status 3. Treat slowly ~ 0.5 meq/l/h

53. Estimate water deficit Water deficit = CBW[plasma Na + /140 – 1] CBW= Current Body Water For males 0.5 X weight For females 0.4 X weight Example: 50kg female has plasma Na + of 183meq/l

54. Example: 50kg female has plasma Na + of 183meq/l Water deficit = 0.4 X 50[183/140-1]=6 liters Time of treatment = (183-140)meq/l =86h 0.5 meq/l/h If no need for quick fluid replacment, treat with 5% glucose. Don’t forget to add insensible loss, ~700 ml/d Estimate continous loss of water and electrolites.

56. Hyponatremia and hypoosmolality = Impaired renal water excretion Hypernatremia and hyperosmolarity = Impaired thirst mechanism or no access to water

57. POLYURIA – D.D. 1.Water diuresis (urine osmolarity 300) Saline loading Postobstructive diuresis Hyperglycemia Very high protein diet Na + wasting nephropathy

58. POLYURIA – DIAGNOSIS 1. Patient history 2. Estimate volume status 3. Measure Glucose level in plasma 4. Plasma osmolarity 5. Urine osmolarity 6. If DI is suspected but no hyperosmolarity is present, perform water restriction test

59. Water restriction test Purpose – to induce hyperosmolarity to stimulate maximal ADH secretion Follow: 1. Plasma osmolarity 2. Urine volume 3. Urine osmolarity When plasma osmolarity > 295 mosmol/l or Urine osmolarity is stable, give exogenous ADH

60. THE END