What are the differential causes of hyponatremia?

Differential Causes of Hyponatremia

Hyponatremia should be classified based on volume status (hypovolemic, euvolemic, or hypervolemic) and plasma osmolality to determine the underlying cause. 1, 2

Classification by Plasma Osmolality

Hypotonic Hyponatremia (Plasma Osmolality <275 mOsm/kg)

This represents true hyponatremia and is the most common form. 3, 4

Isotonic Hyponatremia (Normal Plasma Osmolality 275-290 mOsm/kg)

• Pseudohyponatremia - caused by severe hyperlipidemia or hyperproteinemia (laboratory artifact) 1, 3
• Post-transurethral prostatic resection syndrome - from absorption of irrigation fluid 3

Hypertonic Hyponatremia (Plasma Osmolality >290 mOsm/kg)

• Hyperglycemia - each 100 mg/dL glucose >100 mg/dL decreases sodium by 1.6 mEq/L 1, 3
• Mannitol administration 3

Hypotonic Hyponatremia by Volume Status

Hypovolemic Hyponatremia (ECF Depletion)

Urine Sodium <30 mmol/L (Extrarenal Losses):

• Gastrointestinal losses - vomiting, diarrhea, nasogastric suction 1, 3
• Third-space losses - burns, pancreatitis, peritonitis 1, 3
• Excessive sweating 3

Urine Sodium >20 mmol/L (Renal Losses):

• Diuretic use (especially thiazides) 1, 3, 4
• Cerebral salt wasting (CSW) - particularly in neurosurgical patients with subarachnoid hemorrhage 1, 2, 5
• Adrenal insufficiency 2, 3
• Salt-losing nephropathy 2
• Osmotic diuresis 3

Euvolemic Hyponatremia (Normal ECF)

Urine Sodium >20-40 mmol/L and Urine Osmolality >300 mOsm/kg:

• Syndrome of Inappropriate Antidiuretic Hormone (SIADH) - the most common cause 1, 2, 6
  • Malignancies (especially small cell lung cancer) 2, 5
  • CNS disorders (meningitis, encephalitis, stroke, trauma) 2, 5
  • Pulmonary disease (pneumonia, tuberculosis) 2, 5
  • Medications (SSRIs, carbamazepine, NSAIDs, opiates, antipsychotics) 1, 4
• Hypothyroidism 1, 2
• Glucocorticoid deficiency 2, 3
• Reset osmostat syndrome 3

Urine Sodium <20 mmol/L and Urine Osmolality <100 mOsm/kg:

• Primary polydipsia (psychogenic or dipsogenic) 1, 2
• Beer potomania (excessive beer consumption with poor solute intake) 1, 4
• Acute water intoxication 3

Hypervolemic Hyponatremia (ECF Expansion with Edema)

Urine Sodium >20 mmol/L:

• Advanced renal failure 2, 3

Urine Sodium <20 mmol/L:

• Congestive heart failure 1, 3, 6
• Liver cirrhosis with ascites - affects ~60% of cirrhotic patients 1, 3, 6
• Nephrotic syndrome 3

Key Diagnostic Discriminators

• Serum uric acid <4 mg/dL has 73-100% positive predictive value for SIADH (though may also occur in CSW) 1, 2
• Urinary sodium <30 mmol/L has 71-100% positive predictive value for response to normal saline infusion 1, 2
• Fractional excretion of urea is typically decreased in heart failure due to increased proximal tubular reabsorption 1
• Central venous pressure can help distinguish CSW (CVP <6 cm H₂O) from SIADH (CVP 6-10 cm H₂O) in neurosurgical patients 2

Common Clinical Pitfalls

• Physical examination alone has poor accuracy for determining volume status (sensitivity 41.1%, specificity 80%) 1, 2
• Distinguishing between SIADH and cerebral salt wasting is critical in neurosurgical patients, as treatment approaches differ fundamentally - CSW requires volume replacement while SIADH requires fluid restriction 1, 2, 5
• Even mild hyponatremia (130-135 mmol/L) should not be ignored, as it increases fall risk (21% vs 5%) and mortality (60-fold increase) 1, 6