I. Causes

  1. Usually due to hyperdilution rather than Na depletion. Low-sodium diet can't cause it b/c daily Na requirement is low and renal conservation is very tight
  2. Water intoxication
  3. Anuric or polyuric Renal Failure
  4. SIADH (neoplasms, drugs)-Should see high urine osmolarity
  5. Cerebral sodium wasting-may be separate mechanism from SIADH
  6. Severe intravascular volume depletion, e.g. heart failure or edema
  1. ADH stimulated by hypovolemia, overriding inhibition of ADH secretion by hypotonicity
  2. Usually only causes mild hyponatremia
  1. Adrenal insufficiency
  2. Endurance exercise
    1. Fatal cases have been reported
    2. May involve an SIADH-like phenomen on
    3. Prevention relies on not drinking more than one's "sweat rate" (determined by weighing oneself prior to and after an episode of exercise of similar intensity to, and in similar environment as, the endurance exercise), e.g. no more than 800 mL/h
    4. Risk factors:
      1. Exercise > 4h in duration
      2. Low body weight
      3. Female gender
      4. Overhydration prior to or during exercise (e.g.  > 1.5L/hour of fluid during event (electrolyte-containing "sports drinks" no change in risk)
      5. Extreme environmental heat of cold
      6. NSAID use
  3. Diuretics, mostly thiazides
  1. Usually minor in severity, unless pt drinks only hypotonic fluids
  2. Work by blocking Na reabsorption in tubule, limiting dilution of urine
  3. Can also cause hyponatremia secondary to volume depletion
  4. Treat with H2O restriction, K replacement

II. Pathophysiology-possible mechanisms leading to hyponatremia

  1. Too much ADH
  2. Inadequate GFR or delivery of fluid to disal nephron
  3. Enhanced proximal tubule reabsorption
  4. Defective Na reabsorption in the "diluting segment" (ascending loop and distal convoluted tubule)
  5. Increased H2O permeability in diluting segment

III. Differential diagnosis in a patient with hyponatremia based on volemic state and urine sodium concentration

  1. If hypovolemic:
    1. If urine sodium < 10 mEq/L-Extrarenal Na losses (vomiting, diarrhea, burns, "third-spacing" e.g. due to pancreatitis)
    2. If urine sodium > 20mEq/L-Renal losses (e.g. diuretics, mineralocorticoid deficiency, salt-losing nephropathy, osmotic diuresis)
  2. If euvolemic:
    1. If urine sodium > 20mEq/L-SIADH, glucocorticoid deficiency, hypothyroidism, pain, medications, psychiatric disorders
  3. If hypervolemic:
    1. If urine sodium < 10 mEq/L-Hepatic cirrhosis, heart failure, nephrotic syndrome, glomerulonephritis
    2. If urine sodium > 20mEq/L-Acute renal failure, chronic renal failure


  1. If mild, don't need to treat at all
  2. If due to SIADH, free water restriction will help
  3. If due to decreased effective intravascular volume, don't treat with free water restriction; just makes patient thirsty
  4. If severe, treat with hypertonic saline, e.g. 500 ml 3% NaCl over hours (overly-rapid correction, e.g. > 10-12 mmol/L/24h or > 18 mmol/L/48h may lead to "osmotic demyelination syndome")
  5. Oral vasopressin-receptor antagonists
    1. Conivaptan (Vaprisol)-For treatment of euvolemic hyponatremia, e.g. caused by SIADH
    2. Tolvaptan
(Sources include Core Content Review of Family Medicine, 2012)