eMedicine Specialties > Emergency Medicine > Endocrine & Metabolic

Hyponatremia

Author: Sandy Craig, MD, Adjunct Associate Professor, Department of Emergency Medicine, University of North Carolina at Chapel Hill, Carolinas Medical Center
Contributor Information and Disclosures

Updated: Apr 13, 2010

Introduction

Background

Serum sodium concentration and serum osmolarity normally are maintained under precise control by homeostatic mechanisms involving stimulation of thirst, secretion of antidiuretic hormone (ADH), and renal handling of filtered sodium. Clinically significant hyponatremia is relatively uncommon and is nonspecific in its presentation; therefore, the physician must consider the diagnosis in patients presenting with vague constitutional symptoms or with altered level of consciousness. Irreparable harm can befall the patient when abnormal serum sodium levels are corrected too quickly or too slowly. The physician must have a thorough understanding of the pathophysiology of hyponatremia to initiate safe and effective corrective therapy. The patient's fluid status must be accurately assessed upon presentation, as it guides the approach to correction.

Hypovolemic hyponatremia

Total body water (TBW) decreases; total body sodium (Na⁺) decreases to a greater extent. The extracellular fluid (ECF) volume is decreased.

Euvolemic hyponatremia

TBW increases while total sodium remains normal. The ECF volume is increased minimally to moderately but without the presence of edema.

Hypervolemic hyponatremia

Total body sodium increases, and TBW increases to a greater extent. The ECF is increased markedly, with the presence of edema.

Redistributive hyponatremia

Water shifts from the intracellular to the extracellular compartment, with a resultant dilution of sodium. The TBW and total body sodium are unchanged. This condition occurs with hyperglycemia or administration of mannitol.

Pseudohyponatremia

The aqueous phase is diluted by excessive proteins or lipids. The TBW and total body sodium are unchanged. This condition is seen with hypertriglyceridemia and multiple myeloma.

Pathophysiology

Serum sodium concentration is regulated by stimulation of thirst, secretion of ADH, feedback mechanisms of the renin-angiotensin-aldosterone system, and variations in renal handling of filtered sodium. Increases in serum osmolarity above the normal range (280-300 mOsm/kg) stimulate hypothalamic osmoreceptors, which, in turn, cause an increase in thirst and in circulating levels of ADH. ADH increases free water reabsorption from the urine, yielding urine of low volume and relatively high osmolarity and, as a result, returning serum osmolarity to normal. ADH is also secreted in response to hypovolemia, pain, fear, nausea, and hypoxia.

Aldosterone, synthesized by the adrenal cortex, is regulated primarily by serum potassium but also is released in response to hypovolemia through the renin-angiotensin-aldosterone axis. Aldosterone causes absorption of sodium at the distal renal tubule. Sodium retention obligates free water retention, helping to correct the hypovolemic state. The healthy kidney regulates sodium balance independently of ADH or aldosterone by varying the degree of sodium absorption at the distal tubule. Hypovolemic states, such as hemorrhage or dehydration, prompt increases in sodium absorption in the proximal tubule. Increases in vascular volume suppress tubular sodium reabsorption, resulting in natriuresis and helping to restore normal vascular volume. Generally, disorders of sodium balance can be traced to a disturbance in thirst or water acquisition, ADH, aldosterone, or renal sodium transport.

Hyponatremia is physiologically significant when it indicates a state of extracellular hyposmolarity and a tendency for free water to shift from the vascular space to the intracellular space. Although cellular edema is well tolerated by most tissues, it is not well tolerated within the rigid confines of the bony calvarium. Therefore, clinical manifestations of hyponatremia are related primarily to cerebral edema. The rate of development of hyponatremia plays a critical role in its pathophysiology and subsequent treatment. When serum sodium concentration falls slowly, over a period of several days or weeks, the brain is capable of compensating by extrusion of solutes and fluid to the extracellular space. Compensatory extrusion of solutes reduces the flow of free water into the intracellular space, and symptoms are much milder for a given degree of hyponatremia.

When serum sodium concentration falls rapidly, over a period of 24-48 hours, this compensatory mechanism is overwhelmed and severe cerebral edema may ensue, resulting in brainstem herniation and death.

Frequency

United States

Hyponatremia is the most common electrolyte disorder, with a marked increase among hospitalized and nursing home patients. A 1985 prospective study of inpatients in a US acute care hospital found an overall incidence of approximately 1% and a prevalence of approximately 2.5%. On the surgical ward, approximately 4.4% of postoperative patients developed hyponatremia within 1 week of surgery. Hyponatremia has also been observed in approximately 30% of patients treated in the intensive care unit.¹

International

Though clearly not indicative of the overall prevalence internationally, hyponatremia has been observed in as high as 42.6% of patients in a large acute care hospital in Singapore and in 30% of patients hospitalized in an acute care setting in Rotterdam.^2,3

Mortality/Morbidity

Pathophysiologic differences between patients with acute and chronic hyponatremia engender important differences in their morbidity and mortality.

• Patients with acute hyponatremia (developing over 48 h or less) are subject to more severe degrees of cerebral edema for a given serum sodium level. The primary cause of morbidity and death is brainstem herniation and mechanical compression of vital midbrain structures. Rapid identification and correction of serum sodium level is necessary in patients with severe acute hyponatremia to avert brainstem herniation and death.
• Patients with chronic hyponatremia (developing over more than 48 h) experience milder degrees of cerebral edema for a given serum sodium level. Brainstem herniation has not been observed in patients with chronic hyponatremia. The principal direct causes of morbidity and death are status epilepticus (when chronic hyponatremia reaches levels of 110 mEq/L or less) and cerebral pontine myelinolysis (an unusual demyelination syndrome that occurs in association with chronic hyponatremia).
• The distinction between acute hyponatremia and chronic hyponatremia has critical implications in terms of morbidity and mortality and in terms of proper corrective therapy.
• A 2009 study of 98,411 hospitalized patients found that even mild degrees of hyponatremia were associated with increased in-hospital, 1-year and 5-year mortality rates. Mortality was particularly increased in those with cardiovascular disease, metastatic cancer, and those undergoing orthopedic procedures.⁴
• A 2009 study in Copenhagen concluded that hyponatremia in the range of 130-137 mEq/L is also associated with increased mortality rates in the general population.⁵

Sex

Overall incidence of hyponatremia is approximately equal in males and females, though postoperative hyponatremia appears to be more common in menstruant females.

Age

Hyponatremia is most common in the extremes of age; these groups are less able to experience and express thirst and less able to regulate fluid intake autonomously. Specific settings that have been known to pose particular risk include the following:

• Infants fed tap water in an effort to treat symptoms of gastroenteritis
• Infants fed dilute formula in attempt to ration
• Elderly patients with diminished sense of thirst, especially when physical infirmity limits independent access to food and drink

Clinical

History

• The number and severity of symptoms increase with the degree of hyponatremia and the rapidity with which it develops. When the serum sodium level falls gradually, over a period of several days or weeks, sodium levels as low as 110 mEq/L may be reached with minimal symptomatology. In contrast, an equivalent fall in serum sodium level over 24-48 hours may overwhelm compensatory mechanisms, leading to severe cerebral edema, coma, or brainstem herniation.
• Symptoms range from mild anorexia, headache, and muscle cramps, to significant alteration in mental status including confusion, obtundation, coma, or status epilepticus.
• Hyponatremia is often seen in association with pulmonary/mediastinal disease or CNS disorders. Hyponatremia must be considered in patients with pneumonia, active tuberculosis, pulmonary abscess, neoplasm, or asthma, as well as in patients with CNS infection, trauma, or neoplasm. Patients with carcinoma of the nasopharynx, duodenum, stomach, pancreas, ureter, prostate, or uterus also have an increased risk.
• Hyponatremia is associated with numerous medications. The patient's medication list should be examined for drugs known to cause hyponatremia.
• Hyponatremia has been noted in patients with poor dietary intake who consume large amounts of beer (called beer potomania) and after use of the recreational drug N- methyl-3,4-methylenedioxyamphetamine (ie, MDMA or ecstasy). MDMA-induced hyponatremia occurs via multiple mechanisms; these include the induction of syndrome of inappropriate antidiuretic hormone (SIADH), the encouragement to drink large amounts of water to prevent unpleasant side effects of the drug, and the tendency among those intoxicated to be involved in vigorous physical activity that results in heavy sweating.
• A history of hypothyroidism or adrenal insufficiency should be sought because each is associated with hyposmolar hyponatremia.
• Patients with clinically significant hyponatremia present with nonspecific symptoms attributable to cerebral edema. These symptoms, especially when coupled with a recent history of altered fluid balance, should suggest the possibility of hyponatremia.
  • Anorexia
  • Nausea and vomiting
  • Difficulty concentrating
  • Confusion
  • Lethargy
  • Agitation
  • Headache
  • Seizures

Physical

Physical findings are highly variable and dependent on the degree and the chronicity of hyponatremia. Patients with acutely developing hyponatremia are typically symptomatic at a level of approximately 120 mEq/L. Those patients with chronic hyponatremia tolerate much lower levels.

• Most abnormal findings on physical examination are characteristically neurologic in origin.
  • Level of alertness ranging from alert to comatose
  • Variable degrees of cognitive impairment (eg, difficulty with short-term recall; loss of orientation to person, place, or time; frank confusion or depression)
  • Focal or generalized seizure activity
  • In those patients with acute severe hyponatremia, signs of brainstem herniation, including coma; fixed, unilateral, dilated pupil; decorticate or decerebrate posturing; sudden severe hypertension and respiratory arrest
• In addition to neurologic findings, patients may exhibit signs of hypovolemia or hypervolemia. Determining the hydration status of the patient may help establish the etiology of the hyponatremia and direct subsequent treatment.
  • Dry mucous membranes, tachycardia, diminished skin turgor, and orthostasis suggest hypovolemic hyponatremia due to excessive loss of body fluids and replacement with inappropriately dilute fluids.
  • Pulmonary rales, S₃ gallop, jugular venous distention, peripheral edema, or ascites suggest hypervolemic hyponatremia due to excess retention of sodium and free water (ie, cirrhosis, nephrotic syndrome, congestive heart failure).
  • Patients who lack findings of hypovolemia or hypervolemia are considered to have euvolemic hyponatremia, which is consistent with such etiologies as exogenous free water load, hypothyroidism, cortisol deficiency, or SIADH.
• Other nonspecific signs include muscle weakness and cramping. Rhabdomyolysis is an occasional consequence of hyponatremia and should be considered in patients with muscle pain or tenderness.

Causes

• Hypovolemic hyponatremia develops as sodium and free water are lost and replaced by inappropriately hypotonic fluids, such as tap water, half-normal saline, or dextrose in water. Sodium can be lost through renal or nonrenal routes. Nonrenal routes include GI losses, excessive sweating, third spacing of fluids (eg, ascites, peritonitis, pancreatitis, burns), and cerebral salt-wasting syndrome.
  • Excess fluid losses (eg, vomiting, diarrhea, excessive sweating, GI fistulas or drainage tubes, pancreatitis, burns) that have been replaced primarily by hypotonic fluids
  • Acute or chronic renal insufficiency, in which the patient may be unable to excrete adequate amounts of free water
  • Salt-wasting nephropathy
  • Cerebral salt-wasting syndrome seen in patients with traumatic brain injury, aneurysmal subarachnoid hemorrhage, and intracranial surgery. Cerebral salt-wasting must be distinguished from SIADH because both conditions can cause hyponatremia in neurosurgical patients, and yet the pathophysiology and treatment are different.⁶
  • Prolonged exercise in a hot environment, especially in patients who hydrate aggressively with hyposmolar fluids during exertion. Severe symptomatic hyponatremia has been reported in marathon runners and in recreational hikers in the Grand Canyon.
• Euvolemic hyponatremia implies normal sodium stores and a total body excess of free water. This occurs in patients who take in excess hypotonic fluids.
  • Psychogenic polydipsia, often in psychiatric patients
  • Administration of hypotonic intravenous or irrigation fluids during procedures or in the immediate postoperative period^7,8
  • In one meta-analysis, administration of hypotonic maintenance intravenous fluids to hospitalized children has been associated with an increased incidence of acute hyponatremia compared with administration of isotonic maintenance fluids.⁹
  • Infants who may have been given inappropriate amounts of free water
  • Ingestion of sodium phosphate or sodium picosulfates and magnesium citrate combination as a bowel preparation before colonoscopy or colorectal surgery¹⁰
  • SIADH
• Hypervolemic hyponatremia occurs when sodium stores increase inappropriately.
  • This may result from renal causes such as acute or chronic renal failure, when dysfunctional kidneys are unable to excrete the ingested sodium load. It also may occur in response to states of decreased effective intravascular volume.
  • History of hepatic cirrhosis, congestive heart failure, or nephrotic syndrome, in which patients are subject to insidious increases in total body sodium and free water stores
• Uncorrected hypothyroidism or cortisol deficiency (adrenal insufficiency, hypopituitarism)
• Consumption of large quantities of beer or use of the recreational drug MDMA (ecstasy)
• Hyponatremia can be caused by many medications. Known offenders include acetazolamide, amiloride, amphotericin, aripiprazole, atovaquone, thiazide diuretics, amiodarone, basiliximab, angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors, bromocriptine, carbamazepine, carboplatin, carvedilol, celecoxib, cyclophosphamide, clofibrate, desmopressin, donepezil, duloxetine, eplerenone, gabapentin, haloperidol, heparin, hydroxyurea, indapamide, indomethacin, ketorolac, levetiracetam, loop diuretics, lorcainide, mirtazapine, mitoxantrone, nimodipine, oxcarbazepine, opiates, oxytocin, pimozide, propafenone, proton pump inhibitors, quetiapine, sirolimus, ticlopidine, tolterodine, vincristine, selective serotonin reuptake inhibitors, sulfonylureas, trazodone, tolbutamide, venlafaxine, zalcitabine, and zonisamide.

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