Epidemiology
Etiology
- Ectopic ADH Production: Small cell lung cancer (most common paraneoplastic cause).
- CNS Disorders: Stroke, hemorrhage, infection, trauma, surgery.
- Pulmonary Disease: Pneumonia (esp. bacterial), TB, positive pressure ventilation.
- Drugs: Carbamazepine, Cyclophosphamide, SSRIs, TCAs.
Pathophysiology
- ↑ ADH secretion → receptor-mediated signaling cascade in the distal convoluted tubules and the collecting ducts of the kidneys → build-up of additional water canals (aquaporin-2) in the luminal cell membrane
- Water is drawn out of the urine and into the hyperosmolar kidney tissue → concentration of urine and ↑ Urine osmolality (becomes higher than serum osmolality)
- Water retention → ↓ serum osmolality with transient volume expansion → ↑ ANP, ↑ BNP, and ↓ aldosterone → ↑ urinary sodium and water excretion → normal extracellular fluid volume and low plasma osmolality (euvolemic hyponatremia)
- Osmotic fluid shifts → cerebral edema and ↑ intracranial pressure (may occur in patients with extremely low Na+ levels)
Clinical features
Symptoms of hyponatremia
- Mild
- Anorexia
- Nausea, vomiting
- Headache
- Muscle cramps
- Moderate
- Muscle weakness
- Lethargy
- Confusion
- Severe
- Seizures
- Altered consciousness
Tip
Both SIADH and Primary hyperaldosteronism have no edema. A hyponatremic patient with edema should raise suspicion for other conditions (e.g. congestive heart failure).
Diagnostics
Treatment
- Always treat the underlying cause.
- Asymptomatic/Mild Hyponatremia: Fluid restriction (<800 mL/day) is first-line. Salt tablets can be added.
- Moderate/Severe Hyponatremia: ADH antagonists (e.g., Tolvaptan, Conivaptan). Demeclocycline is a second-line option.
- Severe, Symptomatic (seizures, coma): Hypertonic saline (3% NaCl). Administer slowly.
- Complication of Treatment: Rapid correction of chronic hyponatremia (>8-10 mEq/L in 24h) can cause Osmotic Demyelination Syndrome (ODS), previously known as Central Pontine Myelinolysis. Remember: “From low to high, your pons will die.”