1. Disorders of Water Metabolism

2. What primarily affects Sodium levels in the body?

3. Physiology of water balance Almost all dysnatremias are a result of water balance TBW = 60% total body weight 2/3 ECF compartment with water that is freely diffusable b/w ICF and ECF to maintain identical osmolality So, serum osmolality measures all compartments, i.e. -- when total body water is elevated, osmolality falls ADH – governs the excretion of water by the kidney, which prevents dilution of urine when present

4. Osmolality v. Tonicity Osmolality: total number of particles in an aqueous solution (mosmol/kg H2O) Normal Posm = 275-290 mosmol/kg Effective osmolality (tonicity): particles that can exert osmotic force across membranes, via movement of water into or out of cells Na +, glucose and BUN are major determinants of plasma osmolality Posm = 2 x plasma [Na + ] + [Glucose]/18 + [BUN]/2.8 Effective osmoles (Na +, glucose) exert water shifts unlike urea, ethanol

5. Serum osmolality = 285 to 290

6. What factors regulate the ECF? There are multiple sensors (afferent limb that monitors EABV – amount of arterial blood that fills the arterial circulation) Baroreceptors Low pressure baroreceptors in venous beds that monitor for volume overload – atria, pulmonary vascular bed High pressure barocreceptors (carotids) JG apparatus (located at the thick ascending limb of the Loop of Henle to regulate afferent arteriole) – renin release Efferent limb – primarily renal Regulates rate of sodium excretion, which is most significant in the tubules RAAS system – Ang II ADH – released by posterior pituitary with 1% change in blood osm Catecholamine release – directly stimulates sodium reabsorption at PT and LOH

9. ADH ADH is created in supraoptic and paraventricular nuclei Released as granules travels to posterior pituitary gland where it is released as osmolality increases Site of action is collecting tubule Regulated by plasma osmolality (released at 280-290), volume, stress, nausea, pregnancy

11. Differential for hyponatremia

12. Approach to hyponatremia History and physical often gives clue to etiology of hyponatremia -- so take a good history 1. Check serum osm to make sure – hypotonic hyponatremia – total body water issue 2. Determine volume status Hypovolemic ↓ [Na + ] = ↓↓ TBNa/ ↓ TBW Euvolemic ↓ [Na + ] = ↔ TBNa/ ↑ TBW Hypervolemic ↓ [Na + ] = ↑ TBNa/ ↑↑ TBW

13. Approach to hyponatremia 3. Is ADH response appropriate? Is H2O excretion normal or impaired Uosm < 100 mosmol/kg indicates that ADH is appropriately suppressed Primary polydipsia Reset osmostat (when Posm is below normal) Low solute intake Uosm > 100 mosmol/kg occurs in majority of hyponatremic patients and indicates impaired H2O excretion

15. Hypervolemic Hyponatremia Increased water much greater than sodium Usually states of decreased effective circulating volume CHF, nephrotic syndrome, cirrhosis, renal failure What is urine sodium in these cases?

17. Hypovolemic Hyponatremia Total body sodium loss > total body water loss Determine if sodium loss is renal or extrarenal U[Na] < 10 indicated extrarenal loss (Vomiting, diarrhea, third spacing) U[Na] >20 renal losses (diuretics, mineralocorticoid deficiency, salt-losing nephritis, osmotic diuresis, bicarbonaturia, ketonuria

19. Euvolemic Hyponatremia

21. SIADH - Causes

22. Management of hyponatremia

23. What are the clinical signs and symptoms of hyponatremia?

24. Clinical manifestations Depends on rapidity of fall which does not allow for cerebral adaptation Symptoms typically occurs below 125 mmol/L (if from previously normal levels) Mostly neurologic symptoms Nausea, headache, lethargy, ataxia, psychosis, seizures, coma

25. Symptomatic Hyponatermia Key points: 3% saline only if seizures or other neurologic manifestations (can consider faster infusion) Concomitant lasix helps to eliminate free water Frequent labs absolutely necessary What is the risk of too rapid correction?

26. Chronic Asymptomatic Hyponatermia > 48 hours

27. Case examples An 82 y/o woman is admitted from a nursing home with increasing lethargy and confusion. She has a baseline dementia, but is normally animated and interactive with family and staff. She has had a poor appetite over the past year with significant weight loss, and currently eats very little. Two weeks ago HCTZ was added to her medications. Over the past few days, the nurses note some n/v, no diarrhea, fever or other complaints. On exam, she has some dry oral mucosa but she is not orthostatic. There is no evidence of CHF, ascites or edema. She is awake, but lethargic. Neuro exam is nonfocal. Labs: Na 121 (last 130 4 weeks ago), normal renal/liver function. Serum osm 200, urine osm 220, urine Na 30.

28. Differential for hyponatremia Volume depletion from n/v Thiazide diuretic – how does this cause hyponatremia? Tea and toast SIADH

29. How would you treat this patient? Stop diuretic +/- IVF (given ?SIADH) If you gave patient 1L NS and she had SIADH, what would you expect to happen?