eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Critical Care
Hyponatremia
Updated: Apr 16, 2009
Introduction
Background
Hyponatremia is defined as serum sodium (Na) concentration of less than 135 mEq/L. Plasma Na plays a significant role in plasma osmolality and tonicity (serum osmolarity = 2Na + Glu/18 + BUN/2.8). Changes in plasma osmolality are responsible for the signs and symptoms of hyponatremia and also the complications that happen during treatment in the presence of high-risk factors. Whereas hypernatremia always denotes hypertonicity, hyponatremia can be associated with low, normal, or high tonicity. Hyponatremia is the most common electrolyte disorder encountered in hospitalized patients.
Clinical presentation of hyponatremia happens as a result of a rapid of fall in serum Na and also the absolute level of serum Na. Fifty percent of presenting children develop symptoms when serum Na levels fall below 125 mEq/L, a relatively high level when compared with adults. Although morbidity widely varies, serious complications can arise from hyponatremia and can also happen during treatment. Understanding the pathophysiology and treatment options for hyponatremia is important because significant morbidity and mortality are possible.
Pathophysiology
Hyponatremia can develop because of (1) excessive free water, a common cause in hospitalized patients receiving hypotonic solutions; (2) excessive renal or extrarenal losses of Na or renal retention of free water; (3) rarely, deficient intake of Na.
Under normal circumstances, the human body is able to maintain serum Na in the normal range (135-145 mEq/L) despite wide fluctuations in fluid intake. The body's defense against developing hyponatremia is the kidney's ability to generate dilute urine and excrete free water in response to changes in serum osmolarity and intravascular volume status.
Hospital-acquired hyponatremia is the most common cause of hyponatremia in children. Some studies have outlined the association of hyponatremia and the hypotonic fluid typically used in the pediatric population. Excessive antidiuretic hormone (ADH) is present in most hospitalized patients, either as an appropriate response to hemodynamic and/or osmotic stimuli or as an inappropriate secretion of ADH. ADH is also secreted in response to pain, nausea, and vomiting and during the use of certain medications such as morphine during the postoperative period. Use of hypotonic fluids in presence of circulating ADH can causes free water retention resulting in hyponatremia. In certain clinical conditions, ADH secretion occurs even when serum osmolarity is low or normal, hence the term syndrome of inappropriate ADH secretion (SIADH).
Other conditions that can lead to hyponatremia include states with increased total body water such as with cirrhosis, cardiac failure, or nephrotic syndrome. Diuretic use and decreased intake of Na can also lead to hyponatremia.
Loss of Na via the GI tract and or urinary tract in excess of free water can result in hyponatremia. GI losses can occur in different disease states with excessive fluid loss, namely gastroenteritis, fistulas, or serous fluid drainage after surgery. Na can be lost via the kidney; use of diuretics is the most common culprit, followed by other causes, such as salt-losing nephritis, mineralocorticoid deficiency, and cerebral salt-wasting syndrome (CSWS). Hyponatremia is rarely caused by deficient Na intake.
Clinical manifestations vary from an asymptomatic state to severe neurologic dysfunction. CNS symptoms predominate in hyponatremia, although cardiovascular and musculoskeletal findings may be present. Factors that contribute to CNS symptoms are (1) the rate at which serum Na levels change, (2) the absolute serum Na level, (3) the duration of the abnormal serum Na level, (4) the presence of other CNS pathology risk factors, and (5) the presence of excessive ADH levels.
CNS Effects
Hyponatremia exerts most of its clinical effects on the brain. Brain volume is regulated by equal osmolality of extracellular and intracellular fluid. When extracellular osmolality decreases, water influx occurs in the brain resulting in cerebral edema. Cerebral edema is responsible for symptoms such as headache, nausea, vomiting, irritability, and seizures.If hyponatremia is acute (ie, within hours), the change in osmolality causes influx of water resulting in cerebral edema. If hyponatremia occurs slowly (ie, over days), the brain has adaptive response to protect itself from edema formation. The brain’s adaptive response is mediated through different mechanisms and also modified by different factors as discussed below.
Mechanisms implied in cerebral edema formation include the following:
- Na-K ATPase system
- Aquaporin channels
- Organic osmolytes
The brain’s adaptive response to protect itself from edema occurs over several days. Once the brain has adapted to the hypo-osmolar conditions, a correction of the hypo-osmolar extracellular space to an euvolemic or hyper-osmolar state that is too rapid leads to a rapid efflux of water from brain tissue, resulting in dehydration of brain cells. The resultant condition is called osmotic demyelination syndrome (ODS). Previously, this pathological injury was described only in the pons, hence the term central pontine myelinolysis (CPM). Although it predominantly affects the pons, this condition is now known to occur in other parts of brain as well (see Complications).
Hyponatremic Encephalopathy
Risk factors for hyponatremic encephalopathy include age, sex, hypoxia and vasopressin levels.Sex
Epidemiologic data have shown that the risk for developing permanent neurologic sequelae or death from hyponatremic encephalopathy is substantially higher in menstruating women than in men or postmenopausal women.1 The relative risk of death or permanent neurologic damage due to hyponatremic encephalopathy is about 30 times greater for women than for men and about 25 times greater for menstruating women than for postmenopausal women. Although estrogen hormones have been implicated as the cause of this high incidence of hyponatremic encephalopathy, cellular level mechanisms have now been elucidated. Estrogen has a core steroidal structure similar to cardiac glycosides known to inhibit the Na-K ATPase system, impairing adaptive responses. In addition, estrogen also appears to regulate water movement and neurotransmission by affecting AQP4 expression.
Age
Prepubescent children are at increased risk to develop complications because of hyponatremia. Although many other factors may contribute to this increased risk, brain–to–cranial vault ratio plays an important role. The brain reaches adult size by age 6 years, whereas the skull does not reach adult size until age 16 years. As a consequence, children can develop symptomatic hyponatremia with relatively higher Na concentrations than those observed in adults. Good outcomes are reported in young babies with open fontanelles; increased vault compliance supports this hypothesis.
Hypoxia
Hypoxia is a major risk factor for hyponatremic encephalopathy. Patients with symptomatic hyponatremia can develop hypoxia by 2 different mechanisms: noncardiogenic pulmonary edema and hypercapnic respiratory failure. Hypercapnic respiratory failure is due to central respiratory depression and is often the first sign of impending herniation. Noncardiogenic pulmonary edema, on the other hand, is a complex disorder during with increased vascular permeability and increased catecholamine release that often occurs secondary to elevated intracranial pressure.
Hypoxia worsens clinical outcomes in hyponatremic encephalopathy by impairing the brain’s adaptive response through the active transport of Na, which is an energy-dependent process that requires oxygen. It also affects astrocyte volume regulation, which is also energy dependent. Under ordinary circumstances, hypoxia results in an increase in cerebral blood flow to increase the delivery of oxygen;2 the increase in cerebral blood flow can lead to an increase in cerebral blood volume, which also contributes to an increase in intracranial pressure.
Vasopressin
Hyponatremia, except in cases of pure water intoxication, virtually always occurs in the presence of increased plasma levels of vasopressin. Vasopressin leads to decreased cerebral oxygen use in female rat brain but not in male rats. Vasopressin decreases cerebral blood flow by vasoconstriction, resulting in decreased oxygen delivery that, in turn, impairs brain adaptation. Vasopressin also facilitates direct movement of water into brain cells independent of hyponatremia. In addition, it also decreases synthesis of ATP and phosphocreatine, lowers intracellular pH and intracellular buffering, and decreases Ca2+, which affects energy-dependent processes involved in brain adaptation.
Cardiovascular Response to Hyponatremia
Hyponatremia is also often classified by body water volume status: hyponatremia in conjunction with hypervolemia, euvolemia, or hypovolemia. The distribution of water and solute in the intracellular and extracellular spaces determine the intravascular volume. Fluid shifts from the extracellular space to the intracellular space with a subsequent decrease in arterial blood volume. The reduction in intravascular volume may result in hypotension. Because of this fluid shift, hyponatremia causes hemodynamic disturbance more pronounced than that expected for the degree of dehydration.Frequency
United States
Reported frequency varies from 1-30% among hospitalized pediatric patients.
International
In India, the frequency of hyponatremia is 29.8%.3 It is more frequent in summer (36%) than in winter (24%).
Mortality/Morbidity
Overall morbidity and mortality is 42%.
Sex
The incidence of hyponatremia is equal in both sexes. However, CNS complications are most likely to occur among premenopausal women.
Age
Hyponatremic encephalopathy is most common in prepubescent children.
Clinical
History
The history of patients with hyponatremia may include the following:
- Hypotonic fluid use for maintenance hydration in hospitalized children (potential risk factor)
- Feeding with hypotonic formula or excessive free water during infancy
- Conditions that cause GI, Na-rich fluid loss, including the following:
- Diarrhea
- Vomiting
- Fistulas
- Renal disorders, including the following:
- Salt-losing nephropathy
- Acute renal failure
- Chronic renal failure
- Postoperative states4
- Psychiatric conditions
- Coma
- Drug use
- CNS and pulmonary diseases
- Hypothyroidism
- Adrenal insufficiency
- Cirrhosis
- Congestive heart failure
- Acquired immunodeficiency syndrome (AIDS)
- Cystic fibrosis
Physical
- CNS findings
- Early signs include the following:
- Anorexia
- Headache
- Nausea
- Emesis
- Advanced signs include the following:
- Impaired response to verbal stimuli
- Impaired response to painful stimuli
- Bizarre behavior
- Hallucinations
- Obtundation
- Incontinence
- Respiratory insufficiency
- Seizure activity
- Far-advanced signs include the following:
- Decorticate or decerebrate posturing
- Bradycardia
- Hypertension or hypotension
- Altered temperature regulation
- Dilated pupils
- Seizure activity
- Respiratory arrest
- Coma
- Early signs include the following:
- Cardiovascular findings
- Hypotension
- Tachycardia
- Musculoskeletal findings
- Weakness
- Muscular cramps
Causes
- Hypervolemic hyponatremia (excess free-water retention)
- Congestive heart failure
- Cirrhosis
- Nephrotic syndrome
- Acute or chronic renal failure
- Hypovolemic hyponatremia due to renal loss of sodium in excess of free-water
- Diuretic excess
- Osmotic diuresis
- Salt-wasting diuresis
- Adrenal insufficiency
- Metabolic alkalosis
- Pseudohypoaldosteronism
- Hypovolemic hyponatremia due to extrarenal loss of sodium in excess of free-water
- GI conditions, such as the following:
- Vomiting
- Diarrhea
- Drains
- Fistula
- Sweat
- Cystic fibrosis
- Cerebral salt-wasting syndrome (CSWS)
- Third-spacing conditions, such as the following:
- Pancreatitis
- Burns
- Muscle trauma
- Peritonitis
- Effusions
- Ascites
- GI conditions, such as the following:
- Normovolemic hyponatremia
- Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
- Tumors - Adenocarcinoma of the duodenum, adenocarcinoma of the pancreas, carcinoma of the ureter, carcinoma of the prostate, Hodgkin disease, thymoma, acute leukemia, lymphosarcoma, or histiocytic lymphoma
- Chest disorders - Infection (eg, tuberculosis or bacterial, mycoplasmal, viral, or fungal infection), positive-pressure ventilation, decreased left atrial pressure (eg, due to pneumothorax, atelectasis, asthma, cystic fibrosis, mitral valve commissurotomy, ligation of the patent ductus arteriosus ligation), or malignancy
- CNS disorders - Infection (eg, tuberculous meningitis, bacterial meningitis, encephalitis), trauma, hypoxia-ischemia, psychosis, brain tumor, or miscellaneous CNS disorders (eg, Guillain-Barré syndrome, ventriculoatrial shunt obstruction, acute intermittent porphyria, cavernous sinus thrombosis, multiple sclerosis, anatomic abnormalities, vasculitis, stress, idiopathic causes)
- Drugs
Drugs that impair water excretion.
- Reset osmostat
- Glucocorticoid deficiency
- Hypothyroidism
- Water intoxication due to intravenous (IV) therapy, tap-water enema, or psychogenic water drinking
- Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
More on Hyponatremia |
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| References |
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References
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Further Reading
Keywords
hyponatremia, hypertonicity, hypernatremia, electrolyte abnormality, hospital-acquired hyponatremia, syndrome of inappropriate antidiuretic hormone secretion, SIADH, cardiac failure, cirrhosis, nephrotic syndrome, treatment, diagnosis, gastroenteritis, fistula, salt-wasting nephritis, mineralocorticoid deficiency, cerebral salt-wasting syndrome, CSWS, osmotic demyelination syndrome, ODS, central pontine myelinolysis, CPM, hyponatremic encephalopathy, noncardiogenic pulmonary edema, hypercapnic respiratory failure, dehydration, diarrhea, vomiting, acute renal failure, chronic renal failure, hypothyroidism, adrenal insufficiency
acquired immunodeficiency syndrome, AIDS, cystic fibrosis, hallucinations, obtundation, respiratory insufficiency, seizure activity, hypertension, hypotension, respiratory arrest, congestive heart failure, pancreatitis, adenocarcinoma of the duodenum, adenocarcinoma of the pancreas, carcinoma of the ureter, carcinoma of the prostate, Hodgkin disease, thymoma, acute leukemia, lymphosarcoma, or histiocytic lymphoma, pneumothorax, atelectasis, asthma, cystic fibrosis, mitral valve commissurotomy, ligation of the patent ductus arteriosus ligation, tuberculosis, Guillain-Barré syndrome, ventriculoatrial shunt obstruction, acute intermittent porphyria, cavernous sinus thrombosis, multiple sclerosis, anatomic abnormalities, vasculitis, stress, idiopathic causes
