Hyponatremia

Risk factors

• Diuretic use, especially thiazides (HCTZ, chlorthalidone)
• SIADH triggers: malignancy (small cell lung), CNS disease (stroke, hemorrhage, infection), pulmonary disease (pneumonia, TB), drugs (SSRIs, carbamazepine, MDMA, antipsychotics)
• Heart failure, cirrhosis, nephrotic syndrome (effective arterial underfilling)
• Adrenal insufficiency, hypothyroidism
• Polydipsia (psychogenic, beer potomania, tea-and-toast)
• Postoperative, hypotonic IV fluid administration
• Exercise-associated hyponatremia (marathon runners over-hydrating with hypotonic fluids)

Pathophysiology

True hypotonic hyponatremia results from excess water relative to sodium. ADH-driven water retention exceeds urinary water excretion capacity. Causes are categorized by volume status: hypovolemic (volume loss replaced with hypotonic fluid), euvolemic (SIADH, hypothyroid, adrenal insufficiency), hypervolemic (HF, cirrhosis, CKD/nephrotic — total body Na increased but water more so). Pseudohyponatremia: severe hyperlipidemia or hyperproteinemia causes lab artifact with normal plasma water Na.

Clinical presentation

Differential diagnosis

• Hypovolemic hyponatremia — Volume depletion + low urine Na (<20) + high urine osm; GI losses, diuretics (high urine Na if active), bleeding
• SIADH (euvolemic) — Normal volume, low serum osm, INAPPROPRIATELY concentrated urine (osm >100), urine Na >40, normal thyroid/adrenal function
• Hypothyroidism / adrenal insufficiency — Test TSH, cortisol; mimic SIADH labs; correct hormone deficit
• Polydipsia / low solute intake — Dilute urine (<100 mOsm/kg), high water intake (psychogenic) or low solute (beer potomania)
• Hypervolemic hyponatremia — Edema, ascites; HF, cirrhosis, nephrotic syndrome; urine Na <20 (except CKD)
• Pseudohyponatremia — Severe hyperlipidemia, hyperproteinemia (multiple myeloma); normal measured osmolality
• Translocational hyponatremia — Hyperglycemia, mannitol; correct Na = measured Na + 1.6 × ((glucose - 100)/100)

Diagnostic workup

Diagnostic algorithm

flowchart TD
  A[Serum Na <135] --> B[Serum osmolality]
  B -->|Normal/High| C[Pseudohyponatremia<br/>or hyperglycemia/mannitol]
  B -->|Low <275| D[True hypotonic<br/>hyponatremia]
  D --> E[Assess volume status]
  E -->|Hypovolemic| F[Urine Na]
  F -->|<20| G[Extrarenal loss<br/>GI, skin, blood]
  F -->|>40| H[Renal loss<br/>diuretic, adrenal insuff]
  E -->|Euvolemic| I[Urine osm]
  I -->|<100| J[Primary polydipsia<br/>low solute]
  I -->|>100| K[SIADH, hypothyroid,<br/>adrenal insuff]
  E -->|Hypervolemic| L[HF, cirrhosis,<br/>nephrotic, CKD]

Treatment

Complications

• Osmotic demyelination syndrome (formerly central pontine myelinolysis) — from overly rapid correction; presents days later with dysarthria, dysphagia, paraparesis, locked-in syndrome; irreversible
• Cerebral edema and herniation from severe acute hyponatremia
• Seizures
• Falls and fractures (chronic mild hyponatremia)
• Increased mortality in hospitalized patients

PANCE pearls

• First step in hyponatremia evaluation: check serum osmolality. Low (<275) = true hypotonic; normal = pseudohyponatremia; high = translocational (hyperglycemia, mannitol).
• SIADH diagnostic criteria: hypotonic hyponatremia + euvolemia + urine osm >100 + urine Na >40 + normal thyroid and adrenal function + no diuretics.
• Correct chronic hyponatremia SLOWLY: max 8-10 mEq/L per 24 hours to avoid osmotic demyelination syndrome. Higher-risk patients (alcoholics, malnourished, hypokalemic): even more cautious.
• Acute symptomatic hyponatremia (<48 h): 3% hypertonic saline is appropriate emergency treatment regardless of chronicity concerns.
• Pseudohyponatremia clue: normal serum osmolality despite low measured Na (lab artifact from hypertriglyceridemia, hyperproteinemia).
• Hyperglycemia correction formula: corrected Na = measured Na + 1.6 × ((glucose − 100)/100). Each 100 mg/dL glucose rise lowers Na ~1.6 mEq/L.

References

• European Society 2014 — Clinical practice guideline on diagnosis and treatment of hyponatraemia (Spasovski et al., Eur J Endocrinol 2014)
• Expert Panel 2013 — Diagnosis, Evaluation, and Treatment of Hyponatremia: Expert Panel Recommendations (Verbalis et al., Am J Med 2013)