Hyponatremia

Signs and symptoms

Signs and symptoms of hyponatremia include nausea and vomiting, headache, short-term memory loss, confusion, lethargy, fatigue, loss of appetite, irritability, muscle weakness, spasms or cramps, seizures, and decreased consciousness or coma. The presence and severity of signs and symptoms are related to the level of salt in the blood, with lower levels of plasma sodium associated with more severe symptoms. However, emerging data suggest that mild hyponatremia (plasma sodium levels at 131–135 mmol/L) is associated with numerous complications or subtle, presently unrecognized symptoms (for example, increased falls, altered posture and gait, reduced attention).

Neurological symptoms typically occur with very low levels of plasma sodium (usually <115 mmol/L). When sodium levels in the blood become very low, water enters the brain cells and causes them to swell. This results in increased pressure in the skull and causes hyponatremic encephalopathy. As pressure increases in the skull, herniation of the brain can occur, which is a squeezing of the brain across the internal structures of the skull. This can lead to headache, nausea, vomiting, confusion, seizures, brain stem compression and respiratory arrest, and non-cardiogenic accumulation of fluid in the lungs. This is usually fatal if not immediately treated.

Symptom severity depends on how fast and how severe the drop in blood salt level. A gradual drop, even to very low levels, may be tolerated well if it occurs over several days or weeks, because of neuronal adaptation. The presence of underlying neurological disease such as a seizure disorder or non-neurological metabolic abnormalities, also affects the severity of neurologic symptoms.

Chronic hyponatremia can lead to such complications as neurological impairments. These neurological impairments most often affect gait (walking) and attention, and can lead to increased reaction time and falls. Hyponatremia, by interfering with bone metabolism, has been linked with a doubled risk of osteoporosis and an increased risk of bone fracture.

Causes

The specific causes of hyponatremia are generally divided into those that occur with high fluid volume, those with normal fluid volume, and those with low fluid volume. Too little sodium in the diet alone is very rarely the cause of hyponatremia.

High volume hyponatremia

Both sodium and water content increase: Increase in sodium content leads to hypervolemia and water content to hyponatremia. Total body water and sodium are regulated independently.

Normal volume hyponatremia

There is volume expansion in the body, no edema, but hyponatremia occurs

Low volume hyponatremia

The hypovolemia (extracellular volume loss) is due to total body sodium loss. The hyponatremia is caused by a relatively smaller loss in total body water.

Prolonged periods of exercise may be a cause, known as exercise-associated hyponatremia (EAH). It is common in marathon runners and participants of other endurance events. The use of MDMA can result in hyponatremia. This likely occurs as a result of fluid loss via sweating and replacement with water without electrolytes.

Other causes

Miscellaneous causes of hyponatremia that are not included under the above classification scheme include the following:

Diagnosis

The history, physical exam, and laboratory testing are required to diagnose and determine the underlying cause of hyponatremia. A blood test demonstrating a serum sodium less than 135 mmol/L is diagnostic for hyponatremia. The history and physical exam are necessary to help determine if the patient is hypovolemic, euvolemic, or hypervolemic, which has important implications in determining the underlying cause. An assessment is also made to determine if the patient is experiencing symptoms from their hyponatremia. These include assessments of alertness, concentration, and orientation.

False hyponatremia

False hyponatremia, also known as spurious, pseudo, hypertonic, or artifactual hyponatremia is when the lab tests read low sodium levels but there is no hypotonicity. In hypertonic hyponatremia, resorption of water by molecules such as glucose (hyperglycemia or diabetes) or mannitol (hypertonic infusion) occurs. In isotonic hyponatremia a measurement error due to high blood triglyceride level (most common) or paraproteinemia occurs. It occurs when using techniques that measure the amount of sodium in a specified volume of serum/plasma, or that dilute the sample before analysis.

True hyponatremia

True hyponatremia, also known as hypotonic hyponatremia, is the most common type. It is often simply referred to as "hyponatremia." Hypotonic hyponatremia is categorized in 3 ways based on the person's blood volume status. Each category represents a different underlying reason for the increase in ADH that led to the water retention and thence hyponatremia:

Acute versus chronic

Chronic hyponatremia is when sodium levels drop gradually over several days or weeks and symptoms and complications are typically moderate. Chronic hyponatremia is often called asymptomatic hyponatremia in clinical settings because it is thought to have no symptoms; however, emerging data suggests that "asymptomatic" hyponatremia is not actually asymptomatic.

Acute hyponatremia is when sodium levels drop rapidly, resulting in potentially dangerous effects, such as rapid brain swelling, which can result in coma and death.

Pathophysiology

Sodium is the primary positively charged ion in the environment outside of the cell and cannot freely cross from the interstitial space into the cell. Charged sodium ions attract up to 25 water molecules around them thereby creating a large polar structure too large to pass through the cell membrane.

Treatment

The treatment of hyponatremia depends on the underlying cause and whether the person's blood volume status is high, normal, or low.

Fluids

In the setting of hypovolemia, intravenous administration of normal saline (salt) is usual, care being taken not to raise the serum sodium level (salt level in the blood) too quickly (see below). Euvolemic hyponatremia is usually managed by fluid restriction and treatment to abolish any stimuli for ADH secretion such as nausea. Likewise, drugs causing SIADH are discontinued if possible. Patients with euvolemic hyponatremia that persists despite those measures may be candidates for a so-called vaptan drug as discussed below. Hypervolemic hyponatremia is usually treated by addressing the underlying heart or liver failure. If it is not possible to do so, the treatment becomes the same as that for euvolemic hyponatremia (that is, fluid restriction and/or use of a vaptan drug).

Hyponatremia is corrected slowly, to lessen the risk of the development of central pontine myelinolysis (CPM), a severe neurological disease involving a breakdown of the myelin sheaths covering parts of nerve cells. In fact, overly rapid correction of hyponatremia is the most common cause of that potentially devastating disorder. During treatment of hyponatremia, the serum sodium (salt level in the blood) is not allowed to rise by more than 8 mmol/L over 24 hours (that is, 0.33 mmol/L/h rate of rise). In practice, too rapid correction of hyponatremia and thence CPM is most likely to occur during the treatment of hypovolemic hyponatremia. In particular, once the hypovolemic state has been corrected, the signal for ADH release disappears. At that point, there is an abrupt water diuresis (an increase in urination since there is no longer any ADH acting to retain the water). A rapid and profound rise in serum sodium (salt level in the blood) can then occur. Should the rate of rise of serum sodium exceed 0.33 mmol/L/h over several hours, vasopressin may be administered to prevent ongoing rapid water diuresis (excessive urination).

Medications

There is tentative evidence that vasopressin receptor antagonists (vaptans), such as conivaptan, may be slightly more effective than fluid restriction in those with high volume or normal volume hyponatremia. They should not be used in people with low volume. Their use is SIADH is unclear.

Epidemiology

Hyponatremia is the most common electrolyte disorder. Electrolytes are sodium (salt), potassium, calcium, magnesium, chloride, hydrogen phosphate, and hydrogen carbonate. The disorder is more frequent in females, the elderly, and in people who are hospitalized. The incidence of hyponatremia depends largely on the patient population. A hospital incidence of 15–20% is common, while only 3–5% of people who are hospitalized have a serum sodium level (salt blood level) of less than 130 mmol/L. Hyponatremia has been reported in up to 30% of elderly patients in nursing homes and is also present in approximately 30% of depressed patients on selective serotonin reuptake inhibitors.

People who have hyponatremia who require hospitalisation have a longer length of stay (with associated increased costs) and also have a higher likelihood of requiring readmission. This is particularly the case in men and in the elderly.