What is hypernatremia, its causes, pathophysiology, signs and symptoms, and classification in the elderly, infants, and individuals with underlying medical conditions, such as diabetes insipidus, kidney failure, hyperaldosteronism, or Cushing's syndrome?

Hypernatremia: Definition, Causes, Pathophysiology, Signs and Symptoms, and Classification

Definition

Hypernatremia is defined as a serum sodium concentration greater than 145 mmol/L, representing a state of relative water deficit compared to total body sodium. 1, 2, 3

Pathophysiology

The fundamental mechanism of hypernatremia involves dysfunction of the body's normal water homeostasis, which depends on three critical factors: arginine vasopressin (AVP) secretion, intact thirst mechanism, and appropriate renal response to AVP. 2

• Hypernatremia reflects an imbalance where free water loss exceeds sodium excretion, or less commonly, results from excessive sodium intake 4
• The body normally maintains osmolality between 280-295 mOsm/kg through coordinated AVP release, thirst response, and renal water conservation 2
• When hypernatremia develops, cellular dehydration occurs as water shifts from the intracellular to extracellular compartment to maintain osmotic equilibrium 3
• In chronic hypernatremia (>48 hours), brain cells generate idiogenic osmoles to protect against volume loss, making rapid correction dangerous as it can cause cerebral edema 1, 4

Classification by Volume Status

Hypovolemic Hypernatremia

This occurs from combined water and sodium losses, where water loss exceeds sodium loss, and can result from renal or extrarenal causes. 5, 3

• Renal losses: osmotic diuresis, loop diuretics, post-obstructive diuresis 5
• Extrarenal losses: gastrointestinal losses (diarrhea, vomiting), excessive sweating, burns 6, 5

Euvolemic Hypernatremia

This represents pure water loss with normal total body sodium, most commonly from diabetes insipidus. 3

• Central (neurogenic) diabetes insipidus: caused by traumatic brain injury, neurosurgery, vascular events, infections, or tumors affecting the hypothalamus or posterior pituitary 3
• Nephrogenic diabetes insipidus: results from renal resistance to AVP, commonly caused by lithium therapy, hypokalemia, hypercalcemia, or chronic kidney disease 3
• Insensible losses: respiratory losses in mechanically ventilated patients, fever 5

Hypervolemic Hypernatremia

This occurs from sodium gain exceeding water gain, representing both sodium and water excess. 3

• Acute form: iatrogenic from hypertonic saline or sodium bicarbonate administration 3
• Chronic form: primary hyperaldosteronism, Cushing's syndrome 3

Classification by Duration and Severity

By Duration

• Acute hypernatremia: developing in <24-48 hours 3, 4
• Chronic hypernatremia: developing over >48 hours 4

By Severity

• Mild: 145-150 mmol/L 3
• Moderate: 150-160 mmol/L 3
• Severe/threatening: >160 mmol/L 3

Signs and Symptoms

The clinical manifestations of hypernatremia primarily reflect central nervous system dysfunction from cellular dehydration, with severity correlating to both the degree and rapidity of sodium elevation. 6, 5

Neurological Manifestations

• Altered mental status: confusion, lethargy, irritability progressing to obtundation 6, 5
• Seizures: particularly with rapid development or severe hypernatremia 6
• Coma: in severe cases if untreated 4
• Muscle weakness, tremors, hyperreflexia, or hyporeflexia 5
• Intracranial hemorrhage: from brain shrinkage causing vascular tearing (in acute severe cases) 5

Other Clinical Features

• Intense thirst: in conscious patients with intact thirst mechanism 4
• Signs of volume depletion: in hypovolemic hypernatremia (tachycardia, hypotension, decreased skin turgor, dry mucous membranes) 5
• Signs of volume overload: in hypervolemic hypernatremia (edema, elevated jugular venous pressure) 5

Special Population Considerations

Neonates and Infants

In very low birth weight infants, hypernatremia is often iatrogenic, resulting from incorrect replacement of transepidermal water loss, inadequate water intake, or excessive sodium intake during the transition phase. 1

• Therapeutic measures must be based on assessment of intravascular volume and hydration status 1
• Rapid correction can induce cerebral edema, seizures, and neurological injury; a reduction rate of 10-15 mmol/L/24h is recommended 1, 7
• Some neonates with salt-wasting conditions (Bartter syndrome types 1 and 2) may develop secondary nephrogenic diabetes insipidus, creating a therapeutic dilemma where salt supplementation worsens polyuria and risks hypernatremic dehydration 1

Elderly Patients

Older adults are particularly vulnerable to hypernatremia due to diminished thirst perception, reduced renal concentrating ability, increased comorbidities, and higher use of diuretic medications. 1

• Water homeostasis is more vulnerable with tendency toward both hypo- and hypervolemia 1
• Risk of delirium and confusion is higher during acute illness 1
• Hypophosphatemia during refeeding can provoke acute psychotic changes and delirium, especially when glucose infusion causes rapid intracellular shifts 1

Patients with Underlying Conditions

Diabetes Insipidus:

• Central diabetes insipidus requires desmopressin (DDAVP) replacement in addition to free water 4
• Nephrogenic diabetes insipidus may require thiazide diuretics and dietary sodium restriction 5
• Salt supplementation is contraindicated in patients with secondary nephrogenic diabetes insipidus and hypernatremic dehydration 1

Kidney Failure:

• Impaired urinary concentrating ability increases hypernatremia risk 6
• Renal replacement therapy may be needed for acute severe hypernatremia (<24 hours), but must be initiated cautiously in chronic hypernatremia to avoid rapid sodium drops 4

Hyperaldosteronism and Cushing's Syndrome:

• These cause chronic hypervolemic hypernatremia through excessive mineralocorticoid activity 3
• Treatment focuses on addressing the underlying endocrine disorder 3

Common Pitfalls and Caveats

Critical errors in hypernatremia management can lead to devastating neurological complications:

• Overly rapid correction of chronic hypernatremia (>48 hours) can cause cerebral edema and seizures; correction should not exceed 10-15 mmol/L per 24 hours or 0.5 mmol/L per hour 1, 7, 3
• Using normal saline (0.9% NaCl) as primary rehydration fluid in hypernatremic patients worsens the condition due to its high sodium content (154 mmol/L) 7
• Undercorrection or overcorrection are both associated with poor prognosis and increased mortality 5
• Failing to identify the volume status (hypovolemic vs. euvolemic vs. hypervolemic) leads to inappropriate treatment 5
• In neonates with salt-wasting tubulopathies and secondary nephrogenic diabetes insipidus, salt supplementation paradoxically worsens hypernatremia 1
• Inadequate monitoring of serum sodium during correction (should be checked every 2-4 hours initially) can result in complications 5