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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Question 1RenalMedium
An 82-year-old nursing home resident is brought in with lethargy and decreased oral intake for 5 days. She is afebrile, blood pressure 96/58 mmHg, with dry mucous membranes and poor skin turgor. Serum sodium is 158 mEq/L, BUN 48 mg/dL, creatinine 1.4 mg/dL. Urine osmolality is 720 mOsm/kg. Which of the following is the most appropriate first-line management?
ADesmopressin
B5% dextrose in water
COral free water
DIsotonic saline
Reveal answer & full explanation
Correct answer: D — Isotonic saline
ADesmopressin
B5% dextrose in water
COral free water
DIsotonic saline✓
Why Isotonic saline is correct
This patient has hypovolemic hypernatremia (sodium 158 mEq/L) from inadequate water intake, evidenced by hypotension (BP 96/58 mmHg), dry mucous membranes, poor skin turgor, an elevated BUN-to-creatinine ratio, and appropriately concentrated urine (720 mOsm/kg)
In hypernatremia with hemodynamic instability, the first priority is restoring intravascular volume with isotonic saline before addressing the free water deficit
Once perfusion is restored, the free water deficit is corrected gradually with hypotonic fluids, lowering sodium no faster than 0.5 mEq/L per hour or 10-12 mEq/L per day to prevent cerebral edema
Why the others are wrong
5% dextrose in water — provides free water but is inappropriate as initial therapy in a hypotensive patient and risks too-rapid sodium correction (premature closure on free-water deficit)
Desmopressin — treats central diabetes insipidus; this patient's concentrated urine and clear volume depletion indicate hypovolemic hypernatremia (confused-with diabetes insipidus)
Oral free water — suits mild hypernatremia in an alert, hemodynamically stable patient who can drink, but this lethargic, hypotensive patient cannot reliably take oral fluids, and free water distributes across total body water, leaving little in the intravascular space to correct her hypotension (wrong-priority)
Question 2RenalMedium
An 82-year-old nursing home resident with advanced dementia is brought in for 3 days of progressive lethargy and confusion. Staff report he has been refusing most food and fluids and has had no diarrhea or vomiting. On exam he is afebrile, heart rate is 104/min, and blood pressure is 96/58 mm Hg with a 20 mm Hg orthostatic drop. Mucous membranes are dry, skin turgor is decreased, and his eyes appear sunken. He is somnolent but rousable with intermittent muscle twitching. Serum sodium is 158 mEq/L, serum osmolality is 322 mOsm/kg, and urine osmolality is 780 mOsm/kg. Which of the following best explains his hypernatremia?
ANeurogenic diabetes insipidus
BNephrogenic diabetes insipidus
CHyperglycemic osmotic diuresis
DHypovolemic free-water loss
EHypertonic sodium overload
Reveal answer & full explanation
Correct answer: D — Hypovolemic free-water loss
ANeurogenic diabetes insipidus
BNephrogenic diabetes insipidus
CHyperglycemic osmotic diuresis
DHypovolemic free-water loss✓
EHypertonic sodium overload
Why Hypovolemic free-water loss is correct
Serum Na 158 mEq/L with serum osmolality 322 mOsm/kg confirms a hypertonic state from a free water deficit, not sodium excess.
The concentrated urine (osm 780 mOsm/kg, >700) shows an intact ADH axis appropriately retaining water; the kidney is responding correctly, so the problem is inadequate intake plus extrarenal/insensible losses.
The clinical picture is the classic setup: an elderly demented patient with impaired thirst and restricted water access who develops volume depletion (tachycardia, orthostasis, dry membranes, decreased turgor, sunken eyes) and neurologic symptoms (confusion, muscle twitching).
Management is free water replacement (oral water or D5W/0.45% saline) after restoring perfusion with isotonic fluid, correcting Na no faster than ~10 mEq/L per 24 h to avoid cerebral edema.
Why the others are wrong
Neurogenic diabetes insipidus is ADH deficiency (central DI) causing polyuria with inappropriately dilute urine (osm <300); this patient's urine is maximally concentrated at 780, excluding it.
Nephrogenic diabetes insipidus is renal ADH resistance (lithium, hypercalcemia, hypokalemia) that likewise produces dilute urine which fails to concentrate; it is incompatible with a urine osm of 780.
Hyperglycemic osmotic diuresis drives water loss with an intermediate urine osm of 300-600 and a high urinary solute load; the maximally concentrated urine and absence of an osmotic load argue against it.
Hypertonic sodium overload — tempting because a high serum sodium sounds like too much sodium, and sodium gain from hypertonic saline or sodium bicarbonate does raise Na with a concentrated urine, but it expands extracellular volume, whereas his tachycardia, orthostasis, dry mucous membranes, and decreased turgor show volume depletion from a free water deficit.
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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)
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
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
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 Category
Examples
Urine Osmolality
Treatment
Pure water loss
Insensible (fever), inadequate intake
High (>700)
Free water replacement
Hypotonic fluid loss
GI diarrhea, osmotic diuresis, sweating
Variable (300-700)
Isotonic resuscitation then free water
Central DI
Pituitary surgery, trauma, idiopathic
Low (<300); responds to DDAVP
DDAVP, water replacement
Nephrogenic DI
Lithium, hypercalcemia, hypokalemia, hereditary
Low (<300); no DDAVP response
Remove cause, thiazide, low Na diet
Sodium gain (rare)
Hypertonic saline, NaHCO3, salt poisoning
High
Loop 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); in the elderly 0.5 × kg (men) or 0.45 × 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
Chronic (>48 h or unknown duration): lower Na by no more than ~10 mEq/L per 24 h (~0.5 mEq/L/h) to prevent cerebral edema; acute (<48 h, e.g., salt loading) can be corrected faster (~1 mEq/L/h)
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
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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