What is the most common cause of hypernatremia?

Every cell in the body needs water to survive, but it's possible to get too much or too little of the liquid, and that can cause some pretty serious problems.

The body's fluid balance is not only affected by water that's taken in by consuming food and beverages and released in urine and sweat, but also by the concentration of sodium, an electrolyte. Electrolytes are minerals that carry an electrical charge when dissolved in a liquid such as blood. In the body, sodium is mainly found in the fluid outside of cells and plays an important role in the movement of water into and out of them.

Two different disorders, known as hyponatremia and hypernatremia, may result from changes in the balance of water in the body and levels of sodium in the blood. [How Much Salt Do You Need to Survive?]

Hyponatremia and hypernatremia are primarily disorders of water metabolism, said Dr. David Mount, a kidney specialist and clinical chief of the renal division at Brigham and Women's Hospital in Boston.

In hyponatremia, an excess of water in the body can lead to a low concentration of sodium in the blood, he said. And in hypernatremia, a deficit of water in the body can lead to a high concentration of sodium in the blood.

Hyponatremia is a low concentration of sodium in the blood because of an excessive retention of water, Mount said. In this electrolyte abnormality, there is too much water in the body and this dilutes sodium levels in the bloodstream, he noted.

Hyponatremia occurs when blood sodium goes below normal levels, which is 135 milliequivalents/liter (mEq/L).

When sodium levels in the blood are too low, extra water goes into body cells causing them to swell. This swelling can be especially dangerous for brain cells, resulting in neurological symptoms such as headache, confusion, irritability, seizures or even coma.

The symptoms of hyponatremia may be more serious when blood sodium levels drop very quickly and may be milder when they dip gradually, as that allows the body more time to adjust to the change. Other symptoms of the disorder include muscle cramps or weakness, nausea, vomiting, tiredness and a lack of energy.

Hyponatremia can result from an illness or from taking certain medications. According to the National Kidney Foundation, some of the causes may include:

• Severe vomiting or diarrhea.
• Excessive fluid intake, such as during endurance activities or from excessive thirst.
• Taking diuretics, medications that help flush excess water and sodium from the body.
• Kidney failure, a condition in which the kidneys have difficulty eliminating extra fluid from the body.
• Congestive heart failure, which can lead to a build-up of excess fluid in the body.
• Burns affecting a large area of the body.
• Small cell lung cancer.
• Taking antidepressants, including some commonly used selective serotonin reuptake inhibitors, particularly in older adults.
• Syndrome of inappropriate antidiuretic hormone secretion, a condition in which the body makes too much antidiuretic hormone, causing the body to retain too much water and diluting levels of sodium.

People can also consume excessive amounts of water during exercise and develop hyponatremia, Mount told Live Science. Exercise-associated hyponatremia is more likely to affect endurance athletes, such as marathoners, triathletes and ultra-distance race competitors.

Hyponatremia is not a permanent condition, although certain people may be more prone to the disorder than others because of lifestyle habits or a medical condition.

Treatment for hyponatremia depends on its cause and seriousness. In moderate cases of hyponatremia that are the result of diet, taking diuretics or drinking too much water, a person may need to restrict water intake, consume salty foods — such as bouillon or pretzels — or adjust diuretic intake to raise blood sodium levels.

A person with severe hyponatremia may be given a very concentrated saline solution intravenously. But sodium levels need to be corrected slowly and in a controlled fashion, to prevent swollen brain tissue, Mount said.

Hypernatremia

In hypernatremia, the body contains too little water relative to the amount of sodium, Mount said. This causes sodium levels to become abnormally high in the blood — more than 145 mEq/L — which causes water to move out of body tissues and into the blood in an attempt to equalize the concentration between the two. Water can be lost from brain cells, causing them to shrink, which can be dangerous.

Too much sodium in the blood is a common problem in older adults, especially those who have been hospitalized or are in long-term care facilities, Mount said. The disorder can also affect much younger people: Infants may experience hypernatremia if they have severe diarrhea, for example. [4 Tips for Reducing Sodium in Your Diet]

Besides thirst, many of the symptoms of hypernatremia, such as irritability, restlessness and muscle twitching, affect the central nervous system and stem from a loss of water content from brain cells. In some cases, hypernatremia can be life-threatening. Similar to hyponatremia, other symptoms of hypernatremia include feeling tired or lacking energy, confusion, seizures or coma.

The main cause of hypernatremia usually involves dehydration due to an impaired thirst mechanism or limited access to water, according to the Merck Manual. The disorder can also result from diarrhea or vomiting, taking diuretics or having a high fever.

People who aren't always able to provide water for themselves may be more at risk for hypernatremia. This includes people on tube feedings and those with altered mental status (stroke or dementia), plus people who are very young or very old and frail, according to a review in the New England Journal of Medicine.

Older people are more prone to hypernatremia because their thirst mechanism, kidney function, and hormones regulating salt and water balance may not work as effectively.

The main treatment for hypernatremia is simply to replenish fluids. A person with a mild case of hypernatremia can usually just drink fluids to recover. But in more severe instances, water and a small amount of sodium are given intravenously in controlled amounts over a 48-hour period to slowly reduce sodium levels to a normal range.

Fluid levels are corrected slowly to avoid the risk of cerebral edema, a dangerous condition in which there is swelling of the brain, Mount said.

Hypernatremia can be fatal, and may cause permanent brain damage if not treated properly. Some studies suggest the mortality rate may be more than 50% in hospitalized patients affected by the disorder.

Additional resources:

• Measurement of sodium level in the blood

The diagnosis is based on blood tests indicating that the sodium level is high.

Hypernatremia results from a net water loss or a sodium gain, and it reflects too little water in relation to total body sodium and potassium. In a simplified view, the serum sodium concentration (Na+) can be seen as a function of the total exchangeable sodium and potassium in the body and the total body water. [5] The formula is expressed below:

Na+ = Na+ total body + K+ total body/total body water

Consequently, hypernatremia can only develop as a result of either a loss of free water or a gain of sodium or a combination of both. Hypernatremia by definition is a state of hyperosmolality, because sodium is the dominant extracellular cation and solute. [6]

The normal plasma osmolality (Posm) lies between 275 and 290 mOsm/kg and is primarily determined by the concentration of sodium salts. (Calculated plasma osmolality: 2(Na) mEq/L + serum glucose (mg/dL)/18 + BUN (mg/dL)/2.8). Regulation of the Posm and the plasma sodium concentration is mediated by changes in water intake and water excretion. This occurs via two mechanisms:

• Urinary concentration (via pituitary secretion and renal effects of the antidiuretic hormone arginine vasopressin [AVP]) [7, 8]

• Thirst [9]

In a healthy individual, thirst and AVP release are stimulated by an increase in body fluid osmolality above a certain osmotic threshold, which is approximately 280-290 mOsm/L and is considered to be similar if not identical for both thirst and AVP release. An increased osmolality draws water from cells into the blood, thus dehydrating specific neurons in the brain that serve as osmoreceptors or “tonicity receptors.” It is postulated that the deformation of the neuron size activates these cells (thus acting like mechanoreceptors). On stimulation, they signal to other parts of the brain to initiate thirst and AVP release, resulting in increased water ingestion and urinary concentration, rapidly correcting the hypernatremic state.

Conservation and excretion of water by the kidney depends on the normal secretion and action of AVP and is very tightly regulated. The stimulus for AVP secretion is an activation of hypothalamic osmoreceptors, which occurs when the plasma osmolality reaches a certain threshold (approximately 280 mOsm/kg). At plasma osmolalities below this threshold level, AVP secretion is suppressed to low or undetectable levels. Other afferent stimuli, such as a decrease in effective arterial blood volume, pain, nausea, anxiety, and numerous drugs, can also cause a release of AVP. [10]

AVP is synthesized in specialized magnocellular neurons whose cell bodies are located in the supraoptic and paraventricular nuclei of the hypothalamus. The prohormone is processed and transported down the axon, which terminates in the posterior pituitary gland. From there, it is secreted as active AVP hormone into the circulation in response to an appropriate stimulus (hyperosmolality, hypovolemia).

AVP binds to the V2 receptor located on the basolateral membrane of the principal cells of the renal collection ducts. The binding to this G-protein coupled receptor initiates a signal transduction cascade, leading to phosphorylation of aquaporin-2 and its translocation and insertion into the apical (luminal) membrane, creating "water channels" that enable the absorption of free water in this otherwise water-impermeable segment of the tubular system

Thirst is the body’s mechanism to increase water consumption in response to detected deficits in body fluid. As with AVP secretion, thirst is mediated by an increase in effective plasma osmolality of only 2-3%. Thirst is thought to be mediated by osmoreceptors located in the anteroventral hypothalamus. The osmotic thirst threshold averages approximately 288-295 mOsm/kg. This mechanism is so effective that even in pathologic states in which patients are unable to concentrate their urine (diabetes insipidus) and excrete excessive amounts of urine (10-15 L/d), hypernatremia does not develop because thirst is stimulated and body fluid osmolality is maintained at the expense of profound secondary polydipsia.

Developing hypernatremia is virtually impossible if the thirst response is intact and water available. Thus, sustained hypernatremia can occur only when the thirst mechanism is impaired and water intake does not increase in response to hyperosmolality or when water ingestion is restricted.

Significant hypovolemia stimulates AVP secretion and thirst. Blood pressure decreases of 20-30% result in AVP levels many times those required for maximal antidiuresis.

Hypernatremic states can be classified as isolated water deficits (which are generally not associated with intravascular volume changes), hypotonic fluid deficits, and hypertonic sodium gain.

Acute hypernatremia is associated with a rapid decrease in intracellular water content and brain volume caused by an osmotic shift of free water out of the cells. Within 24 hours, electrolyte uptake into the intracellular compartment results in partial restoration of brain volume. A second phase of adaptation, characterized by an increase in intracellular organic solute content (accumulation of amino acids, polyols, and methylamines), restores brain volume to normal. Some patients complete this adaptive response in less than 48 hours. The accumulation of intracellular solutes bears the risk for cerebral edema during rehydration. The brain cell response to hypernatremia is critical. See the image below.