Hypernatremia

Hypernatremia — a serum sodium above 145 mEq/L — almost always reflects a free water deficit rather than sodium excess. The body's primary defenses against hypernatremia are the thirst mechanism and the kidney's ability to concentrate urine under ADH stimulation. When either fails — impaired thirst, inability to access water, ADH deficiency, or ADH resistance — hypernatremia develops.

Because thirst is such a powerful defense, hypernatremia in a conscious patient with normal thirst and free access to water is unusual. Most cases occur in patients who cannot access or communicate their thirst: elderly patients with cognitive impairment, intubated patients, infants, and patients with altered mental status. Hypernatremia in these populations is often a marker of inadequate free water provision rather than a primary disease process.

The clinical consequences of hypernatremia are primarily neurological. Brain cells shrink as water moves out of cells along the osmotic gradient. Symptoms range from irritability, restlessness, and confusion at mild levels to seizures, coma, and intracranial hemorrhage (from tearing of bridging veins as the brain shrinks away from the skull) at severe levels.

Hypernatremia results from three categories of causes: pure water loss, hypotonic fluid loss, and — rarely — sodium gain.

Pure water loss occurs when free water is lost without solute. Diabetes insipidus (DI) is the paradigmatic cause: central DI from ADH deficiency (pituitary surgery, trauma, infiltrative disease) or nephrogenic DI from ADH resistance (lithium, hypercalcemia, hypokalemia, genetic). The key clue is inappropriately dilute urine — urine osmolality below 300 mOsm/kg in the setting of hypernatremia and hyperosmolality. Insensible losses from fever, sweating, and respiratory losses also cause pure water loss, but the kidney compensates by concentrating urine maximally.

Hypotonic fluid loss occurs when fluid containing less sodium than plasma is lost. Osmotic diuresis — from hyperglycemia, mannitol, or high urea load from enteral feeds — causes loss of hypotonic urine. Diarrhea in infants causes hypotonic stool losses. Loop diuretics cause loss of hypotonic urine. In all these cases, the lost fluid has less sodium than plasma, so the remaining plasma becomes more concentrated.

Sodium gain is the least common cause and is almost always iatrogenic: hypertonic saline administration, sodium bicarbonate infusion, or hypertonic enteral feeds. It is distinguished from water loss by the clinical context and by the absence of signs of volume depletion.

The first diagnostic step is to measure urine osmolality. In a hypernatremic patient, the kidney should be concentrating urine maximally — urine osmolality should be above 700–800 mOsm/kg. If urine osmolality is inappropriately low (below 300 mOsm/kg), the kidney is failing to concentrate urine despite the hyperosmolar stimulus, pointing toward diabetes insipidus.

To distinguish central from nephrogenic DI, administer desmopressin (DDAVP) and measure the urine osmolality response. In central DI, DDAVP increases urine osmolality by more than 50% (the kidney can respond to exogenous ADH). In nephrogenic DI, DDAVP produces little or no response (the kidney is resistant to ADH).

Urine osmolality between 300 and 700 mOsm/kg suggests a partial defect — partial central DI, partial nephrogenic DI, or osmotic diuresis. Clinical context and the response to DDAVP help distinguish these.

The treatment of hypernatremia is free water replacement. The route and rate depend on the severity, the duration, and the clinical setting.

For mild to moderate hypernatremia in a patient who can drink, oral free water is the preferred route — it is the most physiologic and avoids the risks of IV hypotonic fluid. For patients who cannot drink, enteral free water via feeding tube is the next preferred route.

IV free water replacement uses hypotonic fluids: D5W (effectively free water after glucose is metabolized), 0.45% saline (half-normal saline), or 0.2% saline. The choice depends on whether volume repletion is also needed. A patient who is both hypernatremic and volume-depleted should receive isotonic saline first to restore hemodynamic stability, then transition to hypotonic fluids for free water replacement.

The correction rate is critical. For chronic hypernatremia (present for more than 48 hours, or unknown duration), the safe correction rate is no more than 10–12 mEq/L per 24 hours — approximately 0.5 mEq/L per hour. Faster correction causes cerebral edema as the brain's idiogenic osmoles draw water into cells faster than they can be cleared. For acute hypernatremia (developing within 48 hours), faster correction — up to 1 mEq/L per hour — is acceptable because idiogenic osmoles have not had time to accumulate.

Calculate the free water deficit to estimate the volume of replacement needed: Free water deficit = 0.6 × weight (kg) × [(serum Na / 140) − 1]. This is an estimate — frequent monitoring of serum sodium (every 4–6 hours during active correction) is essential to ensure the correction rate is appropriate.

Central DI is treated with desmopressin (DDAVP), a synthetic ADH analogue. It can be given intranasally, orally, or IV/subcutaneously. The dose is titrated to urine output and serum sodium. Patients with central DI who are conscious and have intact thirst can often self-regulate by drinking to thirst — DDAVP is most important in patients who cannot regulate their own intake.

Nephrogenic DI is treated by addressing the underlying cause when possible (stopping lithium, correcting hypercalcemia or hypokalemia). When the cause cannot be reversed, thiazide diuretics (paradoxically) reduce urine output in nephrogenic DI by causing mild volume depletion, which increases proximal tubular reabsorption and reduces the volume delivered to the collecting duct. NSAIDs and amiloride are additional options in selected cases.

Lithium-induced nephrogenic DI deserves special mention: lithium accumulates in collecting duct cells and impairs aquaporin-2 expression. Stopping lithium may not fully reverse the DI if it has been present for years. Amiloride blocks the ENaC channel through which lithium enters collecting duct cells and can reduce lithium accumulation.