Hyponatremia

Epidemiology

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Etiology

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• Most common electrolyte disorder in hospitalized pts
• Euvolemic: SIADH (assoc. w/ small cell lung cancer, CNS disorders, SSRIs, carbamazepine), primary polydipsia, beer potomania.
• Hypovolemic: Diuretics (especially thiazides), GI losses (vomiting, diarrhea), mineralocorticoid deficiency (e.g., Addison disease).
• Hypervolemic: CHF, cirrhosis, nephrotic syndrome, advanced CKD.

Pathophysiology

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Clinical features

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Diagnostics

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• Initial Step: Measure serum osmolality (S_osm) to classify:
  • Hypertonic (>295 mOsm/kg): Due to hyperglycemia or mannitol. Calculate corrected Na⁺:
    • Corrected Na⁺ = Measured Na⁺ + [1.6 × (Glucose - 100) / 100].
    • The body doesn’t actually have a sodium deficit. If you lower the glucose (w/ insulin), water shifts back into cells, and Na⁺ will naturally rise back to normal.
  • Isotonic (275–295 mOsm/kg): Pseudohyponatremia due to hyperlipidemia or hyperproteinemia.
    • A laboratory artifact (illusion) caused by older testing methods
  • Hypotonic (<275 mOsm/kg): True hyponatremia. Proceed to urine studies.
• Next Step: Measure urine osmolality (U_osm): determine ADH is on or off. Under normal physiology, if serum osmolality is low (dilute blood/hyponatremia), the brain should turn off ADH secretion.
  • U_osm <100 mOsm/kg: ADH is off. Primary polydipsia or beer potomania (normal renal diluting capacity).
  • U_osm >100 mOsm/kg: ADH is on. Impaired water excretion. Proceed to volume status + urine sodium (U_Na).
• Key Lab Classifications (Hypotonic w/ U_osm >100):
  • Hypovolemic:
    • U_Na <20 mEq/L: Extrarenal losses (GI, skin, third-spacing).
    • U_Na >20 mEq/L: Renal losses (thiazide diuretics, mineralocorticoid deficiency).
  • Euvolemic:
    • U_Na >40 mEq/L (often >30): SIADH (requires low S_osm <275, high U_osm >100, and normal thyroid/adrenal function).
  • Hypervolemic:
    • U_Na <20 mEq/L: CHF, cirrhosis (decreased effective arterial blood volume).
    • U_Na >20 mEq/L: AKI or CKD.

Treatment

• Severe / Symptomatic (Seizures, Coma, Severe Encephalopathy):
  • First-line: 3% hypertonic saline (100 mL IV bolus, repeat up to 2 times as needed).
  • Goal: Rapidly raise Na⁺ by 4–6 mEq/L to relieve cerebral edema, then switch to maintenance/slow correction.
• Hypovolemic Hyponatremia:
  • First-line: 0.9% Normal Saline (NS) to restore intravascular volume.
  • Warning: Once volume is restored, ADH drops rapidly, risking rapid aquaresis and overcorrection. Monitor Na⁺ closely.
• Euvolemic Hyponatremia (SIADH):
  • First-line: Fluid restriction (typically <1 L/day) + treat underlying cause.
  • Second-line: Oral salt tablets, loop diuretics.
  • Refractory: Demeclocycline or Vaptans (e.g., Tolvaptan).
• Hypervolemic Hyponatremia:
  • First-line: Fluid and sodium restriction + loop diuretics.
• Critical Safety Limit (Chronic Hyponatremia / Unknown Duration):
  • Limit correction rate to <6–8 mEq/L per 24 hours to prevent ODS.
  • Overcorrection rescue: Stop active tx; give D5W +/- DDAVP to rescue and re-lower Na⁺.∂

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Complications

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Osmotic demyelination syndrome (ODS)

• Definition: damage to the myelin sheath of the white matter in the CNS caused by a sudden rise in serum osmolality
• This osmotic gradient pulls water out of brain cells, leading to cell shrinkage, apoptosis, and stripping of myelin sheaths (demyelination), particularly of oligodendrocytes.
• The pons is uniquely susceptible due to its compact structure of gray and white matter, leading to the classic presentation of Central Pontine Myelinolysis (CPM).
• Causes
  • Iatrogenic: rapid correction of chronic hyponatremia
    • High-risk factors for ODS: alcohol use disorder (Malnutrition & Low Solute Intake), malnutrition, liver disease, hypokalemia, initial sodium concentration ≤ 105 mEq/L
  • Rapid changes in other osmotically active solutes (e.g., glucose)
• Clinical features
  • Biphasic course: Initial improvement from hyponatremia correction, followed by neurologic deterioration 2-6 days later.
  • Classic Pontine Sx: Spastic quadriplegia, pseudobulbar palsy (dysarthria, dysphagia), and potentially “locked-in” syndrome.
• Diagnostics
  • MRI brain: T2-hyperintense (bright) signal in the central pons.
    • Rapid Na+ Correction → Oligodendrocyte Death → Demyelination → Tissue Breakdown → Edema (↑ Free Water) → ↑ T2 Signal → Hyperintensity (Brightness) on MRI