Hyponatremia
Hyponatremia or hyponatraemia is a low concentration of sodium in the blood. It is generally defined as a sodium concentration of less than 135 mmol/L, with severe hyponatremia being below 120 mEq/L. Symptoms can be absent, mild or severe. Mild symptoms include a decreased ability to think, headaches, nausea, and poor balance. Severe symptoms include confusion, seizures, and coma; death can ensue.
The causes of hyponatremia are typically classified by a person's body fluid status into low volume, normal volume, or high volume. Low volume hyponatremia can occur from diarrhea, vomiting, diuretics, and sweating. Normal volume hyponatremia is divided into cases with dilute urine and concentrated urine. Cases in which the urine is dilute include adrenal insufficiency, hypothyroidism, and drinking too much water or too much beer. Cases in which the urine is concentrated include syndrome of inappropriate antidiuretic hormone secretion. High volume hyponatremia can occur from heart failure, liver failure, and kidney failure. Conditions that can lead to falsely low sodium measurements include high blood protein levels such as in multiple myeloma, high blood fat levels, and high blood sugar.
Treatment is based on the underlying cause. Correcting hyponatremia too quickly can lead to complications. Rapid partial correction with 3% normal saline is only recommended in those with significant symptoms and occasionally those in whom the condition was of rapid onset. Low volume hyponatremia is typically treated with intravenous normal saline. SIADH is typically treated by correcting the underlying cause and with fluid restriction while high volume hyponatremia is typically treated with both fluid restriction and a diet low in salt. Correction should generally be gradual in those in whom the low levels have been present for more than two days.
Hyponatremia is the most common type of electrolyte imbalance, and is often found in older adults. It occurs in about 20% of those admitted to hospital and 10% of people during or after an endurance sporting event. Among those in hospital, hyponatremia is associated with an increased risk of death. The economic costs of hyponatremia are estimated at $2.6 billion per annum in the United States.
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. Lower levels of plasma sodium are associated with more severe symptoms. However, mild hyponatremia may be associated with complications and subtle symptoms.Neurological symptoms typically occur with very low levels of plasma sodium. 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 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, without low tonicity, and falsely low sodiums. Those with low tonicity are then grouped by whether the person has high fluid volume, normal fluid volume, or low fluid volume. Hyponatremia can also be a possible side effect of COVID-19 vaccination.High volume
Both sodium and water content increase: Increase in sodium content leads to hypervolemia and water content to hyponatremia.- Cirrhosis of the liver
- Congestive heart failure
- Nephrotic syndrome in the kidneys
- Excessive water consumption
Normal volume
- SIADH
- Hypothyroidism
- Not enough ACTH
- Beer potomania
- Normal physiologic change of pregnancy
- Reset osmostat
Low volume
- Any cause of hypovolemia such as prolonged vomiting, decreased oral intake, severe diarrhea
- Diuretic use
- Addison's disease and congenital adrenal hyperplasia in which the adrenal glands do not produce enough steroid hormones
- Isolated hyperchlorhidrosis, a rare genetic disorder which results in a lifelong tendency to lose excessive amounts of sodium by sweating.
- Pancreatitis
- Prolonged exercise and sweating, combined with drinking water without electrolytes is the cause of exercise-associated hyponatremia. It is common in marathon runners and participants of other endurance events.
- The use of MDMA can result in hyponatremia.
Medication
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
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 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 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. If the feedback system is overwhelmed, this is water intoxication with maximally dilute urine and is caused by 1) pathological water drinking beer potomania, 3) overzealous intravenous solute free water infusion, or 4) infantile water intoxication. "Impairment of urine diluting ability related to ADH" occurs in nine situations: 1) arterial volume depletion 2) hemodynamically mediated, 3) congestive heart failure, 4) cirrhosis, 5) nephrosis, 6) spinal cord disease, 7) Addison's disease, 8) cerebral salt wasting, and 9) syndrome of inappropriate antidiuretic hormone secretion.
If the feed-back system is normal, but an impairment of urine diluting ability unrelated to ADH occurs, this is 1) oliguric kidney failure, 2) tubular interstitial kidney disease, 3) diuretics, or 4) nephrogenic syndrome of antidiuresis.
Sodium is the primary positively charged ion outside of the cell and cannot cross from the interstitial space into the cell. This is because charged sodium ions attract around them up to 25 water molecules, thereby creating a large polar structure too large to pass through the cell membrane: "channels" or "pumps" are required.
Cell swelling also produces activation of volume-regulated anion channels which is related to the release of taurine and glutamate from astrocytes.
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 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.
Moreover, cerebral salt wasting, a type of hypovolemic hyponatremia, which may develop days after subarachnoid hemorrhage, neurosurgery, or stroke, has now been identified as a separate condition caused by increased brain-derived natriuretic peptides and requiring volume replacement instead of fluid restriction.