Renal/Urology · PANCE / PANRE

Hypernatremia

Serum Na >145 mEq/L; almost always reflects free water deficit.

Also known as: hypernatremia, high sodium, diabetes insipidus, DI

Overview

Serum sodium concentration >145 mEq/L. Reflects relative free water deficit. Categorized by volume status: hypovolemic (water loss > sodium loss), euvolemic (pure water loss), and hypervolemic (sodium gain > water gain — uncommon).

Epidemiology

Less common than hyponatremia in outpatients but common in hospitalized patients, particularly elderly with impaired thirst, ICU patients, and those with limited water access. Hospital-acquired hypernatremia carries mortality 40-70%.

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Risk factors

  • Impaired thirst or restricted access to water (elderly, infants, intubated, demented, bedridden)
  • Excess water loss: insensible (fever, ventilator, burns), GI (diarrhea, especially osmotic), renal (diuretics, post-obstructive diuresis, recovery from ATN)
  • Diabetes insipidus — central (CNS injury, surgery, idiopathic, infiltrative) or nephrogenic (lithium, hypercalcemia, hypokalemia, hereditary, sickle cell, demeclocycline)
  • Osmotic diuresis: hyperglycemia, hypertonic feeding, mannitol
  • Iatrogenic: hypertonic saline, sodium bicarbonate administration, hypertonic feedings without sufficient free water

Pathophysiology

Plasma sodium concentration is tightly regulated by thirst (primary defense) and ADH-mediated water reabsorption. Hypernatremia occurs only when thirst is impaired or water access restricted (otherwise patients drink to correct). Cellular dehydration in the brain causes neurologic symptoms; chronic hypernatremia leads to generation of intracellular 'idiogenic osmoles' that, if rapidly corrected, cause cerebral edema.

Clinical presentation

Symptoms

  • Thirst (intact thirst mechanism) — if absent, suspect adipsic or impaired access
  • Lethargy, weakness, restlessness
  • Confusion, irritability
  • Muscle twitching, hyperreflexia
  • Seizures, coma (severe — Na >160)
  • Polyuria, polydipsia (in DI)

Signs / physical exam

  • Volume status — usually mildly hypovolemic in classic hypernatremia
  • Hypovolemic: dry mucous membranes, decreased skin turgor, orthostatic hypotension, sunken eyes
  • Tachycardia
  • Altered mental status, focal neurologic deficits in severe or rapidly developing cases
  • Hypervolemic (rare): edema, hypertension, signs of fluid overload

Classic findings

Elderly nursing home resident with poor oral intake presenting with confusion, dry mucous membranes, and Na >150 — classic hypovolemic hypernatremia from inadequate water intake.

Differential diagnosis

  • Hypovolemic hypernatremia — Volume depletion + water loss; weight loss, dry membranes, orthostasis; urine concentrated if extrarenal loss
  • Diabetes insipidus (central) — Polyuria with dilute urine (osm <300); responds to DDAVP (urine osm rises >50%)
  • Diabetes insipidus (nephrogenic) — Polyuria with dilute urine; does NOT respond to DDAVP; lithium, hypercalcemia, hypokalemia
  • Osmotic diuresis — Polyuria with urine osm 300-600 and high urine glucose or urea; hyperglycemia, tube feeds
  • Adipsic hypernatremia — Hypothalamic lesion impairing thirst; chronic, often refractory; managed by scheduled water intake
  • Hypervolemic hypernatremia — Iatrogenic salt loading (3% saline, NaHCO3); volume overload with elevated Na

Diagnostic workup

Diagnostic criteria

Serum Na >145 + clinical context (volume status, urine output, urine osm) determine etiology. DI confirmed by inability to concentrate urine despite hypertonic state; central DI shows >50% increase in urine osm after DDAVP, nephrogenic shows no response.

Labs

  • BMP — serum Na, glucose, creatinine, urea
  • Serum osmolality — confirms hypertonic state
  • Urine osmolality — concentrated (>700) = appropriate ADH response; dilute (<300) = DI; intermediate = partial DI or osmotic diuresis
  • Urine sodium and electrolytes
  • Calcium, potassium (correct hypercalcemia/hypokalemia exacerbating nephrogenic DI)
  • Water deprivation test ± DDAVP challenge to distinguish central vs nephrogenic DI

Imaging

  • MRI pituitary/hypothalamus if central DI suspected (look for stalk lesion, tumor, infiltration; loss of posterior pituitary bright spot on T1)

Diagnostic algorithm

Cause CategoryExamplesUrine OsmolalityTreatment
Pure water lossInsensible (fever), inadequate intakeHigh (>700)Free water replacement
Hypotonic fluid lossGI diarrhea, osmotic diuresis, sweatingVariable (300-700)Isotonic resuscitation then free water
Central DIPituitary surgery, trauma, idiopathicLow (<300); responds to DDAVPDDAVP, water replacement
Nephrogenic DILithium, hypercalcemia, hypokalemia, hereditaryLow (<300); no DDAVP responseRemove cause, thiazide, low Na diet
Sodium gain (rare)Hypertonic saline, NaHCO3, salt poisoningHighLoop diuretic + D5W
Etiologic categories of hypernatremia with characteristic urine findings and treatment approach.

Treatment

First-line

  • Calculate free water deficit: TBW × ((current Na / 140) − 1), where TBW = 0.6 × kg (men) or 0.5 × kg (women)
  • Restore volume first if hemodynamically unstable: isotonic saline (NS or LR) until perfusion adequate
  • Then correct free water deficit with hypotonic fluid: oral water if alert, D5W IV, or 0.45% saline IV
  • Maximum correction rate 10 mEq/L per 24 h (slower if chronic >48 h) to prevent cerebral edema
  • Address ongoing losses (insensible, urinary, GI) plus deficit
  • Treat underlying cause

Second-line / adjunct

  • Central DI: desmopressin (DDAVP) — nasal, oral, or SC; dose-titrated to urine output and Na
  • Nephrogenic DI: low-sodium diet, thiazide diuretic (paradoxically reduces urine output by inducing mild volume depletion), amiloride (for lithium-induced)
  • Stop offending medication if drug-induced (lithium discontinuation may not reverse if long-term)
  • Hypervolemic hypernatremia: loop diuretic + free water replacement (D5W)
  • Monitor Na every 4-6 hours during acute correction

Complications

  • Cerebral edema and seizures from rapid correction (especially chronic hypernatremia)
  • Intracranial hemorrhage (cellular dehydration causes brain shrinkage and bridging vein tearing — especially infants)
  • Subdural hematoma
  • Renal failure (severe hypovolemia)
  • Death — hospital-acquired hypernatremia has 40-70% mortality (often reflects severity of underlying illness)
  • Permanent neurologic injury from acute severe hypernatremia

PANCE pearls

  • Most hypernatremia reflects FREE WATER DEFICIT, not sodium excess. Treatment is water replacement, not sodium restriction.
  • Thirst is a powerful defense against hypernatremia — its presence means the disease is mild; its absence (cognitive impairment, intubation, adipsia) is the setup for severe disease.
  • Diabetes insipidus differentiation: central DI responds to DDAVP (urine osm rises >50%); nephrogenic does not.
  • Correction rate <10 mEq/L per 24 h to avoid cerebral edema — analogous to the cautious approach in chronic hyponatremia.
  • Lithium causes nephrogenic DI in ~20% of patients on chronic therapy; amiloride blocks lithium entry into collecting duct cells.
  • Hospital-acquired hypernatremia is often iatrogenic from inadequate free water replacement in patients with ongoing losses — preventable with careful intake/output tracking.

References

  • Adrogue Madias — Hypernatremia (Adrogué and Madias, NEJM 2000)
  • Sterns 2015 — Disorders of Plasma Sodium — Causes, Consequences, and Correction (Sterns, NEJM 2015)

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