(See also Water and Sodium Balance Water and Sodium Balance Body fluid volume and electrolyte concentration are normally maintained within very narrow limits despite wide variations in dietary intake, metabolic activity, and environmental stresses. Homeostasis... read more and Neonatal Hypernatremia Neonatal Hypernatremia Hypernatremia is a serum sodium concentration > 150 mEq/L (> 150 mmol/L), usually caused by dehydration. Signs include lethargy and seizures. Treatment is cautious hydration with IV saline... read more .)
Etiology of Hypernatremia
Hypernatremia reflects a deficit of total body water (TBW) relative to total body sodium content. Because total body sodium content is reflected by extracellular fluid (ECF) volume status, hypernatremia must be considered along with status of the ECF volume:
Note that the ECF volume is not the same as effective plasma volume. For example, decreased effective plasma volume may occur with decreased ECF volume (as with diuretic use or hemorrhagic shock Shock Shock is a state of organ hypoperfusion with resultant cellular dysfunction and death. Mechanisms may involve decreased circulating volume, decreased cardiac output, and vasodilation, sometimes... read more ), but it may also occur with increased ECF volume (eg, in heart failure Heart Failure (HF) Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular (LV) failure causes shortness of breath and fatigue, and right ventricular (RV) failure causes peripheral and abdominal... read more , hypoalbuminemia, or capillary leak syndrome).
Hypernatremia usually involves an impaired thirst mechanism or limited access to water, either as contributing factors or primary causes. The severity of the underlying disorder that results in an inability to drink in response to thirst and the effects of hyperosmolality on the brain are thought to be responsible for a high mortality rate in hospitalized adults with hypernatremia. There are several common causes of hypernatremia (see table Principal Causes of Hypernatremia Principal Causes of Hypernatremia ).
Hypernatremia associated with hypovolemia occurs with sodium loss accompanied by a relatively greater loss of water from the body. Common extrarenal causes include most of those that cause hyponatremia Hyponatremia Hyponatremia is decrease in serum sodium concentration < 136 mEq/L (< 136 mmol/L) caused by an excess of water relative to solute. Common causes include diuretic use, diarrhea, heart failure... read more and volume depletion. Either hypernatremia or hyponatremia can occur with severe volume loss, depending on the relative amounts of sodium and water lost and the amount of water ingested before presentation.
Renal causes of hypernatremia and volume depletion include therapy with diuretics. Loop diuretics inhibit sodium reabsorption in the concentrating portion of the nephrons and can increase water clearance. Osmotic diuresis can also impair renal concentrating capacity because of a hypertonic substance present in the tubular lumen of the distal nephron. Glycerol, mannitol, and occasionally urea can cause osmotic diuresis resulting in hypernatremia.
The most common cause of hypernatremia due to osmotic diuresis is hyperglycemia in patients with diabetes Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more . Because glucose does not penetrate cells in the absence of insulin, hyperglycemia further dehydrates the intracellular fluid (ICF) compartment. The degree of hyperosmolality in hyperglycemia may be obscured by the lowering of serum sodium resulting from movement of water out of cells into the ECF (translational hyponatremia Hyponatremia Hyponatremia is decrease in serum sodium concentration < 136 mEq/L (< 136 mmol/L) caused by an excess of water relative to solute. Common causes include diuretic use, diarrhea, heart failure... read more ). Patients with renal disease can also be predisposed to hypernatremia when their kidneys are unable to maximally concentrate urine.
Hypernatremia with euvolemia is a decrease in TBW with near-normal total body sodium (pure water deficit). Extrarenal causes of water loss, such as excessive sweating, result in some sodium loss, but because sweat is hypotonic (particularly when people are heat acclimatized), hypernatremia can result before significant hypovolemia. A deficit of almost purely water also occurs in central diabetes insipidus ArginineVasopressin Deficiency (Central Diabetes Insipidus) Arginine vasopressin deficiency (central diabetes insipidus) results from a deficiency of vasopressin (antidiuretic hormone [ADH]) due to a hypothalamic-pituitary disorder. Polyuria and polydipsia... read more and nephrogenic diabetes insipidus Nephrogenic Diabetes Insipidus Nephrogenic diabetes insipidus (NDI) is an inability to concentrate urine due to impaired renal tubule response to vasopressin (ADH), which leads to excretion of large amounts of dilute urine... read more .
Essential hypernatremia (primary hypodipsia) occasionally occurs in children with brain damage and in chronically ill older adults. It is characterized by an impaired thirst mechanism (eg, caused by lesions of the brain’s thirst center). Altered osmotic trigger for vasopressin release is another possible cause of euvolemic hypernatremia; some lesions cause both an impaired thirst mechanism and an altered osmotic trigger. The nonosmotic release of vasopressin appears intact, and these patients are generally euvolemic.
Hypernatremia in rare cases is associated with volume overload. In this case, hypernatremia results from a grossly elevated sodium intake associated with limited access to water. One example is the excessive administration of hypertonic sodium bicarbonate during treatment of lactic acidosis Lactic Acidosis Lactic acidosis is a high anion gap metabolic acidosis due to elevated blood lactate. Lactic acidosis results from overproduction of lactate, decreased metabolism of lactate, or both. (See also... read more . Hypernatremia can also be caused by the administration of hypertonic saline or incorrectly formulated hyperalimentation.
Hypernatremia in older adults
Hypernatremia is common among older adults, particularly postoperative patients and those receiving tube feedings or parenteral nutrition. Other contributing factors may include the following:
Dependence on others to obtain water
Impaired thirst mechanism
Impaired renal concentrating capacity (due to diuretics, impaired vasopressin release, or nephron loss accompanying aging or other renal disease)
Impaired angiotensin II production (which may contribute directly to the impaired thirst mechanism)
Symptoms and Signs of Hypernatremia
The major symptom of hypernatremia is thirst. The absence of thirst in conscious patients with hypernatremia suggests an impaired thirst mechanism. Patients with difficulty communicating or ambulating may be unable to express thirst or obtain access to water. Sometimes patients with difficulty communicating express thirst by becoming agitated.
The major signs of hypernatremia result from central nervous system (CNS) dysfunction due to brain cell shrinkage. Confusion, neuromuscular excitability, hyperreflexia, seizures, or coma may result. Cerebrovascular damage with subcortical or subarachnoid hemorrhage and venous thromboses have been described in children who died of severe hypernatremia.
In chronic hypernatremia, osmotically active substances are generated in CNS cells (idiogenic osmoles) and increase intracellular osmolality. Therefore, the degree of brain cell dehydration and resultant CNS symptoms are less severe in chronic than in acute hypernatremia.
When hypernatremia occurs with abnormal total body sodium, the typical symptoms of volume depletion Volume Depletion Volume depletion, or extracellular fluid (ECF) volume contraction, occurs as a result of loss of total body sodium. Causes include vomiting, excessive sweating, diarrhea, burns, diuretic use... read more or volume overload Volume Overload Volume overload generally refers to expansion of the extracellular fluid (ECF) volume. ECF volume expansion typically occurs in heart failure, kidney failure, nephrotic syndrome, and cirrhosis... read more are present. Patients with renal concentrating defects typically excrete a large volume of hypotonic urine. When losses are extrarenal, the route of water loss is often evident (eg, vomiting, diarrhea, excessive sweating), and the urinary sodium concentration is low.
Diagnosis of Hypernatremia
The diagnosis is by measuring serum sodium. Physical examination is done to determine if volume depletion or overload is also present. In patients who do not respond to simple rehydration or in whom hypernatremia recurs despite adequate access to water, further diagnostic testing is warranted. Determination of the underlying disorder requires assessment of urine volume and osmolality, particularly after water deprivation.
In patients with increased urine output, a water deprivation test Diagnosis is occasionally used to differentiate among several polyuric states, such as central diabetes insipidus ArginineVasopressin Deficiency (Central Diabetes Insipidus) Arginine vasopressin deficiency (central diabetes insipidus) results from a deficiency of vasopressin (antidiuretic hormone [ADH]) due to a hypothalamic-pituitary disorder. Polyuria and polydipsia... read more and nephrogenic diabetes insipidus Nephrogenic Diabetes Insipidus Nephrogenic diabetes insipidus (NDI) is an inability to concentrate urine due to impaired renal tubule response to vasopressin (ADH), which leads to excretion of large amounts of dilute urine... read more .
Treatment of Hypernatremia
Replacement of intravascular volume and of free water
Replacement of both intravascular volume and free water is the main goal of treatment. Oral hydration is effective in conscious patients without significant gastrointestinal dysfunction. In severe hypernatremia or in patients unable to drink because of continued vomiting or mental status changes, IV hydration is preferred. Hypernatremia that has occurred within the last 24 hours should be corrected over the next 24 hours. However, hypernatremia that is chronic or of unknown duration should be corrected over 48 hours, and the serum osmolality should be lowered at a rate of no faster than 0.5 mOsm/L/hour to avoid cerebral edema caused by excess brain solute. The amount of water (in liters) necessary to replace existing deficits may be estimated by the following formula:
where TBW is in liters and is estimated by multiplying weight in kilograms by 0.6 for men and by 0.5 for women; serum sodium can be in mEq/L or mmol/L. This formula assumes constant total body sodium content. In patients with hypernatremia and depletion of total body sodium content (ie, patients who have volume depletion), the free water deficit is greater than that estimated by the formula.
In patients with hypernatremia and ECF volume overload (excess total body sodium content), the free water deficit can be replaced with 5% dextrose in water (D/W), which can be supplemented with a loop diuretic. However, too-rapid infusion of 5% D/W may cause glucosuria, thereby increasing salt-free water excretion and hypertonicity, especially in patients with diabetes mellitus. Other electrolytes, including serum potassium, should be monitored and should be replaced as needed.
In patients with hypernatremia and euvolemia, free water can be replaced using either 5% D/W or 0.45% saline.
Treatment of patients with central diabetes insipidus Treatment Arginine vasopressin deficiency (central diabetes insipidus) results from a deficiency of vasopressin (antidiuretic hormone [ADH]) due to a hypothalamic-pituitary disorder. Polyuria and polydipsia... read more and acquired nephrogenic diabetes insipidus Nephrogenic Diabetes Insipidus Nephrogenic diabetes insipidus (NDI) is an inability to concentrate urine due to impaired renal tubule response to vasopressin (ADH), which leads to excretion of large amounts of dilute urine... read more are discussed elsewhere.
In patients with hypernatremia and hypovolemia, particularly in patients with diabetes with nonketotic hyperglycemic coma, 0.45% saline can be given as an alternative to a combination of 0.9% normal saline and 5% D/W to replenish sodium and free water. Alternatively, ECF volume and free water can be replaced separately, using the formula given previously to estimate the free water deficit. When severe acidosis (pH < 7.10) is present, sodium bicarbonate solution can be added to 5% D/W or 0.45% saline, as long as the final solution remains hypotonic.
Hypernatremia is usually caused by limited access to water or an impaired thirst mechanism, and less commonly by diabetes insipidus.
Manifestations include confusion, neuromuscular excitability, hyperreflexia, seizures, and coma.
Patients who do not respond to simple rehydration or in whom there is no obvious cause may need assessment of urine volume and osmolality, particularly after water deprivation.
Replace intravascular volume and free water orally or intravenously at a rate dictated by how acutely (< 24 hour) or chronically (> 24 hour) the hypernatremia has developed, while watching other serum electrolyte levels (especially potassium and bicarbonate) as well.