Hyponatremia

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. Lower levels of plasma sodium are associated with more severe symptoms. However, mild hyponatremia (plasma sodium levels at 131–135 mmol/L) may be associated with complications and subtle symptoms This is usually fatal if not immediately treated. Symptom severity depends on how fast and how severe the drop in blood sodium level is. 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. 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 with low tonicity (lower than normal concentration of solutes), without low tonicity, and falsely low sodiums. High volume Both sodium and water content increase: Increase in sodium content leads to hypervolemia and water content to hyponatremia. • Cirrhosis of the liver • SIADH (and its many causes) • Reset osmostat Low volume Hypovolemia (extracellular volume loss) is due to total body sodium loss. Hyponatremia is caused by a relatively smaller loss in total body water. It is common in marathon runners and participants of other endurance events. • The use of MDMA (ecstasy) can result in hyponatremia. Medication Antipsychotics have been reported to cause hyponatremia in a review of medical articles from 1946 to 2016. Available evidence suggests that all classes of psychotropics, i.e., antidepressants, antipsychotics, mood stabilizers, and sedative/hypnotics can lead to hyponatremia. Age is a significant factor for drug induced hyponatremia. Other causes Miscellaneous causes that are not included under the above classification scheme include the following: • False or pseudo hyponatremia is caused by a false lab measurement of sodium due to massive increases in blood triglyceride levels or extreme elevation of immunoglobulins as may occur in multiple myeloma. • Hyponatremia with elevated tonicity can occur with high blood sugar, causing a shift of excess free water into the serum. == Pathophysiology ==

The causes of and treatments for hyponatremia can only be understood by having a grasp of the size of the body fluid compartments and subcompartments and their regulation; how under normal circumstances the body is able to maintain the sodium concentration within a narrow range (homeostasis of body fluid osmolality); conditions can cause that feedback system to malfunction (pathophysiology); and the consequences of the malfunction of that system on the size and solute concentration of the fluid compartments. Normal homeostasis There is a hypothalamic-kidney feedback system which normally maintains the concentration of the serum sodium within a narrow range. This system operates as follows: in some of the cells of the hypothalamus, there are osmoreceptors which respond to an elevated serum sodium in body fluids by signalling the posterior pituitary gland to secrete antidiuretic hormone (ADH) (vasopressin). ADH then enters the bloodstream and signals the kidney to bring back sufficient solute-free water from the fluid in the kidney tubules to dilute the serum sodium back to normal, and this turns off the osmoreceptors in the hypothalamus. Also, thirst is stimulated. Normally, when mild hyponatremia begins to occur, that is, the serum sodium begins to fall below 135 mEq/L, there is no secretion of ADH, and the kidney stops returning water to the body from the kidney tubule. Also, no thirst is experienced. These two act in concert to raise the serum sodium to the normal range. Hyponatremia Hyponatremia occurs 1) when the hypothalamic-kidney feedback loop is overwhelmed by increased fluid intake, 2) the feedback loop malfunctions such that ADH is always "turned on", 3) the receptors in the kidney are always "open" regardless of there being no signal from ADH to be open; or 4) there is an increased ADH even though there is no normal stimulus (elevated serum sodium) for ADH to be increased. Hyponatremia occurs in one of two ways: either the osmoreceptor-aquaporin feedback loop is overwhelmed, or it is interrupted. If it is interrupted, it is either related or not related to ADH. == Diagnosis ==

The history, physical exam, and laboratory testing are required to 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 person is hypovolemic, euvolemic, or hypervolemic, which has important implications in determining the underlying cause. An assessment is also made to determine if the person is experiencing symptoms from their hyponatremia. These include assessments of alertness, concentration, and orientation. Short synacthen test (ACTH stimulation test) is essential as early endocrine evaluation in patients with suspected adrenal insufficiency to avoid misdiagnosis of life-threatening hypoadrenalism that can be devoid of classical hyperkalemia and hypotension. 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: • High volume hyponatremia, wherein there is decreased effective circulating volume (less blood flowing in the body) even though total body volume is increased (by the presence of edema or swelling, especially in the ankles). The decreased effective circulating volume stimulates the release of anti-diuretic hormone (ADH), which in turn leads to water retention. Hypervolemic hyponatremia is most commonly the result of congestive heart failure, liver failure, or kidney disease. • Normal volume hyponatremia, wherein the increase in ADH is secondary to either physiologic but excessive ADH release (as occurs with nausea or severe pain) or inappropriate and non-physiologic secretion of ADH, that is, syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH). Often categorized under euvolemic is hyponatremia due to inadequate urine solute (not enough chemicals or electrolytes to produce urine) as occurs in beer potomania or "tea and toast" hyponatremia, hyponatremia due to hypothyroidism or central adrenal insufficiency, and those rare instances of hyponatremia that are truly secondary to excess water intake. • Low volume hyponatremia, wherein ADH secretion is stimulated by or associated with volume depletion (not enough water in the body) due to decreased effective circulating volume. 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. == Treatment ==

The treatment of hyponatremia depends on the underlying cause. • Moderate and/or symptomatic hyponatremia is treated by raising the serum sodium level by 0.5 to 1 mmol per liter per hour for a total of 8 mmol per liter during the first day with the use of furosemide and replacing sodium and potassium losses with 0.9% saline. • Severe hyponatremia or severe symptoms (confusion, convulsions, or coma): consider hypertonic saline (3%) 1–2 mL/kg IV in 3–4 h. Hypertonic saline may lead to a rapid dilute diuresis and fall in the serum sodium. It should not be used in those with an expanded extracellular fluid volume. Electrolyte abnormalities In persons with hyponatremia due to low blood volume (hypovolemia) from diuretics with simultaneous low blood potassium levels, correction of the low potassium level can assist with correction of hyponatremia. 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. Demeclocycline, while sometimes used for SIADH, has significant side effects including potential kidney problems and sun sensitivity. In many people it has no benefit while in others it can result in overcorrection and high blood sodium levels. Rapid correction of sodium levels can also lead to central pontine myelinolysis (CPM). It is recommended not to raise the serum sodium by more than 10 mEq/L/day. == Epidemiology ==

Hyponatremia is the most commonly seen water–electrolyte imbalance. 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. == References ==