creation date: 2025-09-29 16:37
tags: Pathologies
Hypernatremia
Background
Definitions
Hypernatremia refers to an excess of sodium relative to the water content of the body. The relevance of water content is due to sodium (and its anions) making up most of the effective osmoles in the extracellular fluid.
As such, serum sodium represents the water content of the body more so than the sodium levels and thus the approach to etiology, evaluation, and treatment revolves around water.
Tonicity refers to the activity of solutes (in most cases, sodium) that do not easily cross cell membrane. As water can freely move across membranes, tonicity effectively dictates water movement, cell volume, and volume status.
- Hypertonicity refers to a high plasma sodium concentration
- Hypotonicity refers to a low plasma sodium concentration
It should be noted that hypernatremia due to water depletion is referred to as dehydration (compared to hypovolemia which involves depletion of water and salt).
Etiology
There are three mechanisms which can cause hypernatremia.
Unreplaced water losses (most common by far)
- Skin loss (both insensible and sensible) - most sodium is removed from sweat
- Gastrointestinal loss - gastric (vomiting or drainage), small intestine secretion, osmotic diarrheas
- Urinary losses - AVP deficiency or osmotic diuresis (eg. glucouria)
- Hypothalamic lesions - affecting thirst/osmoreceptor function (eg. adipsic diabetes insipidus)
Water loss into cells
- Transient hypernatremia induced by:
- Severe exercise
- Electroshock-induced seizures
- Administration of potassium for hypokalemia (intracellular movement of potassium moves water with it)
- Typically returns to normal within 5-15 minutes
Sodium overload
- Salt poisoning - more common in infants due to accidental salt use (eg. in place of sugar)
- Iatrogenic sodium loading - administration of isotonic saline that is equivalent to hypertonic such as during treatment of uncontrolled diabetes
Pathogenesis
Sodium is a largely extracellular solute, owing to Na-K-ATPase pumping Na out and K in. Approximately 30% are bound to large ployanionic molecules (proteoglycans) which are components of bone, cartilage, and connective tissue. Binding of sodium allows for excess sodium to accumulate without altering serum sodium and affecting cell volume.
In the pathogenesis of hypernatremia, the concentration of sodium in serum rises. This is most commonly due to water loss which concentrates the sodium within the plasma. However, administration/ingestion of sodium can also increase sodium levels.
In normal physiology, increases in plasma tonicity stimulates release of arginine vasopressin (AVP; aka ADH), which minimizes water loss, and thirst, for water repletion.
However, in patients who cannot respond to thirst or lacks a thirst response, hypernatremia can develop.
Clinical Presentation
Signs & Symptoms
Acute hypernatremia (eg. following incorrect infusion) can result in rapid decrease in brain volume:
- Focal intracerebral and subarachnoid hemorrhages
- Neurologic damage
- Demyelinating brain lesions
These manifest as:
- Initially: lethargy, weakness, irritability
- Progress: twitching, seizures, coma
It should be noted that chronic hypernatremia rarely present with neurologic symptoms due to cerebral adaptation (or if there is may be difficult due to unrelated neurologic conditions). As such, assessment may be difficult.
History & Physical Exam
History may find evidence of fluid loss (eg. diarrhea, diuretic use).
Physical examination may find signs of dehydration. It should be noted that signs of dehydration can be underestimated due to extracellular water shift.
Risk factors
Hypernatremia is primarily seen in infants and elderly population. In both these populations, there is an elevated risk in inadequate fluid intake.
Hospitalized patients are also at risk due to the inability to manage own thirst and relying on the care team to prescribe adequate fluid delivery.
Diagnosis
Criteria
Hypernatremia is defined as a serum sodium >145 mmol/L.
It is classified as acute if the hypernatremia has been present for ≤48 hours and chronic is longer.
Work-up
The workup is primarily used to elucidate etiology if it is not evident. This can consist of:
- Volume assessment:
- Hypovolemic - osmotic diuresis, GI losses, sweating
- Euvolemic - water loss
- Hypervolemic - sodium overload
- Urine osmolality which:
- Low (<300 mosmol/kg) suggests AVP deficiency or resistance
- Intermediate (300-600 mosmol/kg) may be due to osmotic diuresis or AVP disorder
- High (>700 mosmol/kg) suggests AVP is normal and losses is likely extrarenal
If diabetes insipidus is suspected, further testing can be done to confirm diagnosis.
Differential
The differential consist of the varying etiology of hypernatremia.
Red Flags / Complications
In acute cases, neurologic damage can be irreversible and rapid treatment should be done. Chronic hypernatremia is also associated with higher levels of mortality.
Management
Fluid repletion
As hypernatremia actually describe a fluid depleted state, the mainstay treatment is fluid repletion.
Calculation of water deficit
Water deficit = Current TBW x ((Serum [Na] / 140) - 1)
- Total body water (TBW) = 60% and 50% of lean body weight of male and female, respectively
- 10% of TBW should be subtracted to account for volume depleted state of hypernatremia
Example: 60 kg female with sodium of 168 mmol/L:
Chronic hypernatremia
In chronic setting, there is much lower urgency. As such, a slower rate of repletion should be used to avoid adverse effects.
This is typically a 5% dextrose in water at 1.35 mL/kg/hr up to a maximum of 150 mL/hr. The regimen’s goal is a correction rate of lowering 10 mmol/L in 24 hours, avoiding exceding by 12 mmol/L in 24 hours.
Acute hypernatremia
In acute cases, more rapid repletion is warranted to avoid complications.
- Salt poisoning: as fast as possible (at least 6 mL/kg/hr) with 5% dextrose in water /hypotonic IV fluids or emergency hemodialysis
- AVP disorder: 3-6 mL/kg/hr of 5% dextose in water
- If central, add desmopressin
- If nephrogenic, use thiazide diuretics
- Hyperglycemia: either swap to 2.5% dextose or use non-glucose fluid option such as Ringer’s lactate
Limiting further water loss
Correction of underlying conditions will likely be necessary to prevent further recurrence. This would depend on etiology.