What causes hypernatremia?

Causes of Hypernatremia

Hypernatremia (Na >145 mmol/L) most commonly results from inadequate water intake relative to losses, rather than from pure sodium excess, with iatrogenic causes being particularly frequent in hospitalized patients. 1

Primary Mechanisms

Hypernatremia reflects an imbalance where water content is deficient compared to sodium content in body fluids 2. The condition develops when dysfunction occurs in the three key regulatory mechanisms: arginine vasopressin (AVP) secretion, thirst mechanism, and renal response to AVP 3.

Major Etiologic Categories

Hypovolemic Hypernatremia (Water Loss Exceeds Sodium Loss)

Renal losses:

• Osmotic diuresis from hyperglycemia or mannitol administration 4
• Excessive diuretic use, particularly in patients with liver disease 1
• Loop diuretics causing hypotonic fluid loss 5

Extrarenal losses:

• Gastrointestinal losses from diarrhea, vomiting, fistulas, or drainage tubes 1
• Excessive sweating, particularly in endurance athletes without adequate water replacement 1
• Transepidermal water loss, especially critical in very low birth weight infants 6, 1

Euvolemic Hypernatremia (Pure Water Loss)

Diabetes insipidus:

• Central (neurogenic): Traumatic brain injury, neurosurgery, vascular events, infections, or tumors affecting the hypothalamus or pituitary 4
• Nephrogenic: Lithium therapy (most common pharmacologic cause), hypokalemia, hypercalcemia, chronic kidney disease 4, 5

Insensible losses:

• Impaired thirst mechanism in elderly or neurologically impaired patients 5
• Lack of access to water in hospitalized or institutionalized patients 5

Hypervolemic Hypernatremia (Sodium Gain)

Acute causes:

• Hypertonic saline or sodium bicarbonate infusions 4
• Excessive sodium administration in parenteral nutrition 1
• Inadvertent sodium intake during the neonatal transition phase 6

Chronic causes:

• Primary hyperaldosteronism 4
• Cushing syndrome 4

High-Risk Clinical Contexts

Pediatric Populations

In very low birth weight infants, hypernatremia is predominantly iatrogenic, resulting from incorrect replacement of transepidermal water loss, inadequate water intake, or excessive sodium intake during the transition phase 6, 1. This population requires particularly careful monitoring as they have immature renal tubular function and high insensible water losses 6.

Hospitalized Patients

Inadequate fluid prescription represents the most common iatrogenic cause in hospital settings 1. This occurs when maintenance fluids fail to account for ongoing losses or when hypotonic losses are replaced with isotonic solutions 2.

Athletes

Excessive sweating without adequate free water replacement during endurance exercise can produce hypernatremia, though this is less common than exercise-associated hyponatremia 1.

Critical Diagnostic Distinction

Urine osmolality and sodium measurements are essential to determine whether kidneys are appropriately concentrating urine and help differentiate between renal and extrarenal causes 1. In diabetes insipidus, urine osmolality remains inappropriately low (<300 mOsm/kg) despite elevated serum osmolality 3.

Common Pitfalls

• Overlooking iatrogenic causes: Always review all fluid orders, parenteral nutrition composition, and medication lists for sodium-containing preparations 6, 1
• Assuming pure dehydration: Hypernatremia rarely results from pure sodium excess, but this must be excluded by assessing volume status 2, 4
• Missing medication-induced nephrogenic diabetes insipidus: Lithium is the classic culprit, but other medications can impair renal concentrating ability 4
• Failing to assess access to water: Particularly in elderly, institutionalized, or neurologically impaired patients who cannot communicate thirst or access fluids independently 5