1. SODIUM HOMEOSTASIS Mohammed Almeziny BsPharm R,Ph. Msc PhD Clinical Pharmacist

2. Introduction  Sodium is the principle cation of extracellular fluid  The regulation of osmolarity (80%).  The acid-base balance.  The membrane potential of cells.

3. Introduction Cont’d  The total is 4200 mmol (60mmol/kg).  40% bone 50% extracellular 10 intracellular.

4. Daily requirement  1-3 mmol/kg/day  1 liter of 0.9% provides 154 mmol N+

6. HYPONATREMIA

7. Definition  Serum sodium concentration less than 132 mmol/l  The sodium con.. Is a reflection of water balance rather than total body sodium.

8. Type of hyponatremia  Hypovolemic hyponatremia  Euvolemic hyponatremia  Hypervolemic hyponatremia  Redistributive hyponatremia  Pseudohyponatremia

9. Hypovolemic hyponatremia  A decrease in total body water (TBW) and a greater decrease in total body sodium (Na + ) occur. The extracellular fluid (ECF) volume is decreased.

10. Euvolemic hyponatremia  An increase in TBW with normal total sodium occurs. The ECF volume is increased minimally to moderately, but edema is not present.

11. Hypervolemic hyponatremia  An increase in total body sodium and a greater increase in TBW occur. The ECF is increased markedly, and edema is present.

12. Redistributive hyponatremia  A shift of water from the intracellular to the extracellular compartment occurs with a resultant dilution of sodium. The TBW and total body sodium are unchanged. This condition occurs with hyperglycemia.

13. Pseudohyponatremia  A dilution of the aqueous phase by excessive proteins or lipids occurs. The TBW and total body sodium are unchanged. This condition is seen with hypertriglyceridemia and multiple myeloma.

14. Diagnostic approach to hyponatremia Normal (280mOsm) Elevated (>280mOsm) Low (<280 mOsm) Measure serum Osmolality Isotonic hyponatremia Hypertonic hyponatremia Clinically asses ECF volume Next slide Hyperlipidemia Hyperproteinemia Isotonic infision Hyperglycemia Hypertonic infusion

15. Low ( BP, HR) poor skin turgor Elevated (edema) Normal Hypovolemic Hypotonic hyponatremia hypervolemic Hypotonic hyponatremia Isovolemic Hypotonic hyponatremia Total body Na deficit GI, skin,lung kidney Adrenal insufficiency Total body Na excess CHF, Liver damage Nephrosis Total body Na normal H2O intoxication SIADH, Renal Failure K loss Reset Osmstat Diagnostic approach to hyponatremia cont’d

16. Interpreting Lab. Data  Urinary Sodium help to distinguish between renal and nonrenal losses.  urine sodium < 20 mEq/L.  e.g cirrhosis, nephrosis, congestive heart failure  SIADH will have urine sodium levels in excess of 20 mEq/L.

17. Causes  Drugs. thiazide diuretics, amiodarone, chlorpropamide, cyclophosphamide, clofibrate, carbamazepine, oxcarbazepine, opiates, oxytocin, desmopressin, vincristine, selective serotonin reuptake inhibitors, trazodone or tolbutamide

18. Causes cont’d  Adrenal Insufficiency and Adrenal Crisis Congestive Heart Failure and Pulmonary Edema Gastroenteritis Hypothyroidism and Myxedema Coma Renal Failure, Acute Renal Failure, Chronic and Dialysis Complications Syndrome of Inappropriate Antidiuretic Hormone Secretion(SIADH).

19. Clinical presentation  Depend on the degree and the chronicity of hyponatremia.  120 mEq/L  110 mEq/L  Most abnormalities on physical exam are neurological in origin.

20. Clinical presentation cont’d  Anorexia  Nausea and vomiting  Difficulty concentrating  Confusion  Lethargy  Agitation  Headache  Seizures

21. Calculate adult Na deficit in hyponatremia  Na mEq.= (140 mEq/L - patient's serum Na) x (0.5X body weight).  An increase in serum sodium of 4-6 mEq/L is generally sufficient  0.5 mEq/L/hr or 12 mEq/L/day or 18 mEq/L/2 day’s.

22. Hypernatremia

23. Definition  Serum sodium concentration More than 145 mmol/l  The sodium con.. Is a reflection of water balance rather than total body sodium.

24. Etiology and Pathophysiology  Hypernatremia in adults has a mortality of 40 to 60%.  The elderly are particularly susceptible, especially in warm weather, due to a reduced thirst response and underlying diseases.

25. Principal Causes of Hypernatremia  Extrarenal losses  GI: Vomiting, diarrhea  Skin: Burns, excessive sweating  Renal losses  Intrinsic renal disease  Loop diuretics  Osmotic diuresis (glucose, urea, mannitol) Hypernatremia with hypovolemia (decreased TBW and Na; relatively greater decrease in TBW)

26. Principal Causes of Hypernatremia cont’d  Extrarenal losses  Respiratory: Tachypnea  Skin: Fever, excessive sweating  Renal losses  Central diabetes insipidus  Nephrogenic diabetes insipidus  Other  Inability to access water  Primary hypodipsia  Reset osmostat Hypernatremia with euvolemia (decreased TBW; near-normal total body Na)

27. Principal Causes of Hypernatremia cont’d  Hypertonic fluid administration (hypertonic saline, NaHCO3, total parenteral nutrition)  Mineralocorticoid excess  Adrenal tumors secreting deoxycorticosterone  Congenital adrenal hyperplasia (caused by 11- hydroxylase defect) Hypernatremia with hypervolemia rare

28. Symptoms and Signs  The major signs of hypernatremia result from CNS dysfunction due to brain cell shrinkage. Confusion, neuromuscular excitability, seizures, or coma may result; cerebrovascular damage with subcortical or subarachnoid hemorrhage and venous thromboses are frequent in patients dying from severe hypernatremia.

29. Treatment  Free water deficit = TBW × [(plasma Na/140) − 1] TBW × [(plasma Na/140) − 1] TBW = body wt x 0.6 = liters  if hypernatremia is chronic or of unknown duration, it should be corrected over 48 h, and the plasma osmolality should be lowered at a rate of no more than 2 mOsm/L/h to avoid cerebral edema caused by excess brain solute.  Loop diuretics

30. Treatment cont’d  In patients with hypernatremia and depletion of total body Na content (ie, who have volume depletion), the free water deficit is greater than that estimated by the formula.  In patients with hypernatremia and ECF volume overload (excess total body Na content), the free water deficit can be replaced with 5% D/W, which can be supplemented with a loop diuretic.

31. Treatment cont’d  In patients with hypernatremia and euvolemia, free water can be replaced using either 5% D/W or 0.45% saline.