Hyponatremia or hyponatraemia is a low concentration of
sodium
Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable iso ...
in the
blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...
.
[ It is generally defined as a sodium concentration of less than 135 ]mmol/L
Molar concentration (also called molarity, amount concentration or substance concentration) is a measure of the concentration of a chemical species, in particular of a solute in a solution, in terms of amount of substance per unit volume of solut ...
(135 mEq/L
An equivalent (symbol: officially equiv; unofficially but often Eq) is the amount of a substance that reacts with (or is ''equivalent'' to) an arbitrary amount (typically one mole) of another substance in a given chemical reaction. It is an arc ...
), with severe hyponatremia being below 120 mEq/L.[ Symptoms can be absent, mild or severe.][ Mild symptoms include a decreased ability to think, ]headache
Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches.
Headaches can occur as a result ...
s, nausea, and poor balance. Severe symptoms include confusion, seizures
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...
, and coma
A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
; 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
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
, vomiting
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose.
Vomiting can be the result of ailments like food poisoning, gastroenteri ...
, diuretics
A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics i ...
, 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
Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by excessive unsuppressible release of antidiuretic hormone (ADH) either from the posterior pituitary gland, or an abnormal non-pituitary source. Unsuppressed ADH ca ...
(SIADH).[ High volume hyponatremia can occur from ]heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
, liver failure, and kidney failure
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
.[ Conditions that can lead to falsely low sodium measurements include high blood protein levels such as in ]multiple myeloma
Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, an ...
, high blood fat levels, and high blood sugar
Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even ...
.
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
Saline (also known as saline solution) is a mixture of sodium chloride (salt) and water. It has a number of uses in medicine including cleaning wounds, removal and storage of contact lenses, and help with dry eyes. By injection into a vein i ...
.[ 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
Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes in the body. Electrolytes play a vital role in maintaining homeostasis in the body. They help to regulate heart and neurological function, ...
, 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
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
and vomiting
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose.
Vomiting can be the result of ailments like food poisoning, gastroenteri ...
, headache
Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches.
Headaches can occur as a result ...
, short-term memory loss
Amnesia is a deficit in memory caused by brain damage or disease,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be caused temporarily by the use o ...
, confusion
In medicine, confusion is the quality or state of being bewildered or unclear. The term "acute mental confusion" , lethargy
Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overwo ...
, fatigue, loss of appetite
Anorexia is a medical term for a loss of appetite. While the term in non-scientific publications is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while others i ...
, irritability
Irritability (also called as crankiness) is the excitatory ability that living organisms have to respond to changes in their environment. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessi ...
, muscle weakness, spasms or cramp
A cramp is a sudden, involuntary, painful skeletal muscle contraction or overshortening associated with electrical activity; while generally temporary and non-damaging, they can cause significant pain and a paralysis-like immobility of the aff ...
s, seizures
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...
, and decreased consciousness or coma
A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
. 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 (for example, increased falls, altered posture and gait, reduced attention, impaired cognition, and possibly higher rates of death).
Neurological
Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal ...
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 (cerebral edema
Cerebral edema is excess accumulation of fluid ( edema) in the intracellular or extracellular spaces of the brain. This typically causes impaired nerve function, increased pressure within the skull, and can eventually lead to direct compres ...
). This results in increased pressure in the skull and causes ''hyponatremic encephalopathy''. As pressure increases in the skull, herniation of the brain
Brain herniation is a potentially deadly side effect of very high pressure within the skull that occurs when a part of the brain is squeezed across structures within the skull. The brain can shift across such structures as the falx cerebri, the te ...
can occur, which is a squeezing of the brain across the internal structures of the skull. This can lead to headache, nausea, vomiting, confusion, seizure
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with l ...
s, brain stem
The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is co ...
compression and respiratory arrest
Respiratory arrest is a sickness caused by apnea (cessation of breathing) or respiratory dysfunction severe enough it will not sustain the body (such as agonal breathing). Prolonged apnea refers to a patient who has stopped breathing for a long p ...
, 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.
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
Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...
and an increased risk of bone fracture
A bone fracture (abbreviated FRX or Fx, Fx, or #) is a medical condition in which there is a partial or complete break in the continuity of any bone in the body. In more severe cases, the bone may be broken into several fragments, known as a '' ...
.
Causes
The specific causes of hyponatremia are generally divided into those with low tonicity (lower than normal concentration of solutes
In chemistry, a solution is a special type of homogeneous mixture composed of two or more substances. In such a mixture, a solute is a substance dissolved in another substance, known as a solvent. If the attractive forces between the solvent ...
), 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.][ Too little sodium in the diet alone is very rarely the cause of hyponatremia.
]
High volume
Both sodium and water content increase: Increase in sodium content leads to hypervolemia and water content to hyponatremia.
* Cirrhosis
Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...
of the liver[
* ]Congestive heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, ...
[
* Nephrotic syndrome in the kidneys][
* Excessive drinking of fluids][
]
Normal volume
There is volume expansion in the body, no edema, but hyponatremia occurs
* SIADH
Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by excessive unsuppressible release of antidiuretic hormone (ADH) either from the posterior pituitary gland, or an abnormal non-pituitary source. Unsuppressed ADH ca ...
(and its many causes)[
* Hypothyroidism][
* Not enough ]ACTH
Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important c ...
[
* ]Beer potomania
Potomania (From Latin ''pōtō'' "I drink (liquor)" + mania) is a specific hypo-osmolality syndrome related to massive consumption of beer, which is poor in solutes and electrolytes. With little food or other sources of electrolytes, consumpti ...
* Normal physiologic change of pregnancy
Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occurs by sexual intercourse, but ca ...
* Reset osmostat The osmostat is the regulatory center in the hypothalamus that controls the osmolality of the extracellular fluid. The area in the anterior region of the hypothalamus contains the osmoreceptors, cells that control osmolality via the secretion of a ...
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.
* Any cause of hypovolemia such as prolonged vomiting, decreased oral intake, severe diarrhea[
* Diuretic use (due to the diuretic causing a volume depleted state and thence ADH release, and not a direct result of diuretic-induced urine sodium loss)][
* ]Addison's disease
Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adre ...
and congenital adrenal hyperplasia
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders characterized by impaired cortisol synthesis. It results from the deficiency of one of the five enzymes required for the synthesis of cortisol in the adrenal cort ...
in which the adrenal gland
The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which ...
s do not produce enough steroid hormones (combined glucocorticoid and mineralocorticoid deficiency
Hypoaldosteronism is an endocrinological disorder characterized by decreased levels of the hormone aldosterone. Similarly, isolated hypoaldosteronism is the condition of having lowered aldosterone without corresponding changes in cortisol. (The ...
)[
* ]Pancreatitis
Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types: acute pancreatitis, and chronic pancr ...
[
* Prolonged exercise and sweating, combined with drinking water without electrolytes is the cause of ]exercise-associated hyponatremia
Exercise-associated hyponatremia, is a fluid-electrolyte disorder caused by a decrease in sodium levels (hyponatremia) during or up to 24 hours after prolonged physical activity. This disorder can develop when marathon runners or endurance event at ...
(EAH).[ It is common in marathon runners and participants of other endurance events.
* The use of ]MDMA
3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in Tablet (pharmacy), tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for Recreational dru ...
(ecstasy) can result in hyponatremia.
Medication
Antipsychotics
Antipsychotics, also known as neuroleptics, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but ...
have been reported to cause hyponatremia in a review of medical articles from 1946 to 2016.
Available evidence suggests that all classes of psychotropics
A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior.
T ...
, i.e., antidepressants
Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...
, antipsychotics
Antipsychotics, also known as neuroleptics, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but ...
, mood stabilizers, and sedative/hypnotics
Hypnotic (from Greek ''Hypnos'', sleep), or soporific drugs, commonly known as sleeping pills, are a class of (and umbrella term for) psychoactive drugs whose primary function is to induce sleep (or surgical anesthesiaWhen used in anesthesia ...
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
A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from ''tri-'' and ''glyceride'').
Triglycerides are the main constituents of body fat in humans and other vertebrates, as w ...
levels or extreme elevation of immunoglobulin
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
s as may occur in multiple myeloma
Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, an ...
.[
* Hyponatremia with elevated tonicity can occur with ]high blood sugar
Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even ...
, 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
Body fluids, bodily fluids, or biofluids, sometimes body liquids, are liquids within the human body. In lean healthy adult men, the total body water is about 60% (60–67%) of the total body weight; it is usually slightly lower in women (52-55% ...
compartments and subcompartments and their regulation; how under normal circumstances the body is able to maintain the sodium concentration within a narrow range (homeostasis
In biology, homeostasis (British English, British also homoeostasis) Help:IPA/English, (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physics, physical, and chemistry, chemical conditions maintained by organism, living systems. Thi ...
of body fluid
Body fluids, bodily fluids, or biofluids, sometimes body liquids, are liquids within the human body. In lean healthy adult men, the total body water is about 60% (60–67%) of the total body weight; it is usually slightly lower in women (52-55% ...
osmolality
Molality is a measure of the number of moles of solute in a solution corresponding to 1 kg or 1000 g of solvent. This contrasts with the definition of molarity which is based on a specified volume of solution.
A commonly used unit for molali ...
); 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
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
, there are osmoreceptors
An osmoreceptor is a sensory receptor primarily found in the hypothalamus of most homeothermic organisms that detects changes in osmotic pressure. Osmoreceptors can be found in several structures, including two of the circumventricular organs – t ...
which respond to an elevated serum sodium in body fluids by signalling the posterior pituitary gland to secrete antidiuretic hormone (ADH) (vasopressin
Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travel ...
). 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. If the feedback system is overwhelmed, this is water intoxication with maximally dilute urine and is caused by 1) pathological water drinking ( psychogenic polydipsia), 2) beer potomania
Potomania (From Latin ''pōtō'' "I drink (liquor)" + mania) is a specific hypo-osmolality syndrome related to massive consumption of beer, which is poor in solutes and electrolytes. With little food or other sources of electrolytes, consumpti ...
, 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 (SIADH).
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 channel
Volume-regulated anion channels (VRACs) are crucial to the regulation of cell size by transporting chloride ions and various organic osmolytes, such as taurine or glutamate, across the plasma membrane, and that is not the only function these chann ...
s which is related to the release of taurine
Taurine (), or 2-aminoethanesulfonic acid, is an organic compound that is widely distributed in animal tissues. It is a major constituent of bile and can be found in the large intestine, and accounts for up to 0.1% of total human body weight. I ...
and glutamate
Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...
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.
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 chemical biology, tonicity is a measure of the effective osmotic pressure gradient; the water potential of two solutions separated by a partially-permeable cell membrane. Tonicity depends on the relative concentration of selective membrane ...
. In hypertonic hyponatremia, resorption of water by molecules such as glucose (hyperglycemia or diabetes) or mannitol
Mannitol is a type of sugar alcohol used as a sweetener and medication. It is used as a low calorie sweetener as it is poorly absorbed by the intestines. As a medication, it is used to decrease pressure in the eyes, as in glaucoma, and to lo ...
(hypertonic infusion) occurs. In isotonic hyponatremia a measurement error due to high blood triglyceride level (most common) or paraprotein
A myeloma protein is an abnormal antibody (immunoglobulin) or (more often) a fragment thereof, such as an immunoglobulin light chain, that is produced in excess by an abnormal monoclonal proliferation of plasma cells, typically in multiple myelo ...
emia 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:
* 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
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, ...
, 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
Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by excessive unsuppressible release of antidiuretic hormone (ADH) either from the posterior pituitary gland, or an abnormal non-pituitary source. Unsuppressed ADH ca ...
(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.[ How quickly treatment is required depends on a person's symptoms.][ Fluids are typically the cornerstone of initial management.][ In those with severe disease an increase in sodium of about 5 mmol/L over one to four hours is recommended.][ A rapid rise in serum sodium is anticipated in certain groups when the cause of the hyponatremia is addressed thus warranting closer monitoring in order to avoid overly rapid correction of the blood sodium concentration. These groups include persons who have hypovolemic hyponatremia and receive intravenous fluids (thus correcting their hypovolemia), persons with adrenal insufficiency who receive ]hydrocortisone
Hydrocortisone is the name for the hormone cortisol when supplied as a medication. Uses include conditions such as adrenocortical insufficiency, adrenogenital syndrome, high blood calcium, thyroiditis, rheumatoid arthritis, dermatitis, asthm ...
, persons in whom a medication causing increased ADH release has been stopped, and persons who have hyponatremia due to decreased salt and/or solute intake in their diet who are treated with a higher solute diet. If large volumes of dilute urine are seen, this can be a warning sign that overcorrection is imminent in these individuals.
Sodium deficit = (140 – serum sodium) x total body water
Total body water = kilograms of body weight x 0.6
Fluids
Options include:
* Mild and asymptomatic hyponatremia is treated with adequate solute intake (including salt and protein) and fluid restriction starting at 500 millilitres per day (mL/d) of water with adjustments based on serum sodium levels. Long-term fluid restriction of 1,200–1,800 mL/d may maintain the person in a symptom-free state.
* 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
Furosemide is a loop diuretic medication used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It may also be used for the treatment of high blood pressure. It can be taken by injection into a vein or by mouth ...
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.
Medications
American and European guidelines come to different conclusions regarding the use of medications.[ In the United States they are recommended in those with SIADH, cirrhosis, or heart failure who fail limiting fluid intake.][ In Europe they are not generally recommended.]
There is tentative evidence that vasopressin receptor antagonist A vasopressin receptor antagonist (VRA) is an agent that interferes with action at the vasopressin receptors. Most commonly VRAs are used in the treatment of hyponatremia, especially in patients with congestive heart failure, liver cirrhosis or SIAD ...
s (vaptans), such as conivaptan
Conivaptan, sold under the brand name Vaprisol, is a non-peptide inhibitor of the receptor for anti-diuretic hormone, also called vasopressin. It was approved in 2004 for hyponatremia (low blood sodium levels). The compound was discovered by As ...
, 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.][ They may also be used in people with chronic hyponatremia due to SIADH that is insufficiently responsive to fluid restriction and/or sodium tablets.]
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.[
Daily use of ]urea
Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid.
Urea serves an important r ...
by mouth, while not commonly used due to the taste, has tentative evidence in SIADH.[ However, it is not available in many areas of the world.][
]
Precautions
Raising the serum sodium concentration too rapidly may cause osmotic demyelination syndrome
Central pontine myelinolysis is a neurological condition involving severe damage to the myelin sheath of nerve cells in the ''pons'' (an area of the brainstem). It is predominately iatrogenic (treatment-induced), and is characterized by acute par ...
. 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.[ The disorder is more frequent in females, the elderly, and in people who are hospitalized. The number of cases of hyponatremia depends largely on the population. In hospital it affects about 15–20% of people; however, only 3–5% of people who are hospitalized have a sodium level less than 130 mmol/L. Hyponatremia has been reported in up to 30% of the elderly in nursing homes and is also present in approximately 30% of people who are depressed on ]selective serotonin reuptake inhibitor
Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions.
SSRIs increase the extracellul ...
s.
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
Further reading
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External links
Hyponatremia
at the Mayo Clinic
Sodium
at Lab Tests Online
ICD-10 code for Hyponatremia
- Diagnosis Code
{{Electrolyte abnormalities
Electrolyte disturbances
Mineral deficiencies
Sodium
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