Hiponatremia

Hyponatremia is defined as a decrease in the serum sodium concentration to a level below 136 mmol per liter. Whereas hypernatremia always denotes hypertonicity, hyponatremia can be associated with low, normal, or high tonicity.1,2 Effective osmolality or tonicity refers to the contribution to osmolality of solutes, such as sodium and glucose, that cannot move freely across cell membranes, thereby inducing transcellular shifts in water.3 Dilutional hyponatremia, by far the most common form of the disorder, is caused by water retention. If water intake exceeds the capacity of the kidneys to excrete water, dilution of body solutes results, causing hypo-osmolality and hypotonicity (Figure 1BFigure 1Extracellular-Fluid and Intracellular-Fluid Compartments under Normal Conditions and during States of Hyponatremia., 1E, 1F, and 1G). Hypotonicity, in turn, can lead to cerebral edema, a potentially life-threatening complication.4 Hypotonic hyponatremia can be associated, however, with normal or even high serum osmolality if sufficient amounts of solutes that can permeate cell membranes (e.g., urea and ethanol) have been retained (Figure 1C). Importantly, patients who have hypotonic hyponatremia but normal or high serum osmolality are as subject to the risks of hypotonicity as are patients with hypo-osmolar hyponatremia.
The nonhypotonic hyponatremias are hypertonic (or translocational) hyponatremia, isotonic hyponatremia, and pseudohyponatremia.1,2 Translocational hyponatremia results from a shift of water from cells to the extracellular fluid that is driven by solutes confined in the extracellular compartment (as occurs with hyperglycemia or retention of hypertonic mannitol); serum osmolality is increased, as is tonicity, the latter causing dehydration of cells (Figure 1D). Retention in the extracellular space of large volumes of isotonic fluids that do not contain sodium (e.g., mannitol) generates iso-osmolar and isotonic hyponatremia but no transcellular shifts of water. Pseudohyponatremia is a spurious form of iso-osmolar and isotonic hyponatremia identified when severe hypertriglyceridemia or paraproteinemia increases substantially the solid phase of plasma and the sodium concentration is measured by means of flame photometry.1,2 The increasing availability of direct measurement of serum sodium with the ion-specific electrode has all but eliminated this laboratory artifact.5
A common clinical problem, hyponatremia frequently develops in hospitalized patients.6 Although morbidity varies widely in severity, serious complications can arise from the disorder itself as well as from errors in management. In this article, we focus on the treatment of hyponatremia, emphasizing a quantitative approach to its correction.

Causes

Hypotonic (dilutional) hyponatremia represents an excess of water in relation to existing sodium stores, which can be decreased, essentially normal, or increased (Figure 1). Retention of water most commonly reflects the presence of conditions that impair renal excretion of water1,7,8; in a minority of cases, it is caused by excessive water intake, with a normal or nearly normal excretory capacity (Table 1Table 1Causes of Hypotonic Hyponatremia.).7
Conditions of impaired renal excretion of water are categorized according to the characteristics of the extracellular-fluid volume, as determined by clinical assessment (Table 1).9 With the exception of renal failure, these conditions are characterized by high plasma concentrations of arginine vasopressin despite the presence of hypotonicity.10,11 Depletion of potassium accompanies many of these disorders and contributes to hyponatremia, since the sodium concentration is determined by the ratio of the “exchangeable” (i.e., osmotically active) portions of the body's sodium and potassium content to total body water (Figure 1G).12-14 Patients with hyponatremia induced by thiazides can present with variable hypovolemia or apparent euvolemia, depending on the magnitude of the sodium loss and water retention.1,15-17
Excessive water intake can cause hyponatremia by overwhelming normal water excretory capacity (e.g., primary polydipsia) (Table 1). Frequently, however, psychiatric patients with excessive water intake have plasma arginine vasopressin concentrations that are not fully suppressed and urine that is not maximally dilute, thus contributing to water retention.18,19
Hyperglycemia is the most common cause of translocational hyponatremia (Figure 1D). An increase of 100 mg per deciliter (5.6 mmol per liter) in the serum glucose concentration decreases serum sodium by approximately 1.7 mmol per liter, with the end result a rise in serum osmolality of approximately 2.0 mOsm per kilogram of water.1 Retention of hypertonic mannitol, which occurs in patients with renal insufficiency, has the same effect. In both conditions, the resultant hypertonicity can be aggravated by osmotic diuresis; moderation of hyponatremia or frank hypernatremia can develop, since the total of the sodium and potassium concentrations in the urine falls short of that in serum.20
Massive absorption of irrigant solutions that do not contain sodium (e.g., those used during transurethral prostatectomy) can cause severe and symptomatic hyponatremia. Reflecting the composition of the irrigant, the resultant hyponatremia can be either hypotonic (with an irrigant containing 1.5 percent glycine or 3.3 percent sorbitol) or isotonic (with an irrigant containing 5 percent mannitol). Whether the symptoms derive from the presence of retained solutes, the metabolic products of such solutes, hypotonicity, or the low serum sodium concentration itself remains unclear.21,22
The most common causes of severe hyponatremia in adults are therapy with thiazides, the postoperative state and other causes of the syndrome of inappropriate secretion of antidiuretic hormone, polydipsia in psychiatric patients, and transurethral prostatectomy.1,17,23-25 Gastrointestinal fluid loss, ingestion of dilute formula, accidental ingestion of excessive water, and receipt of multiple tap-water enemas are the main causes of severe hyponatremia in infants and children.17,26

Clinical Manifestations

Just as in hypernatremia, the manifestations of hypotonic hyponatremia are largely related to dysfunction of the central nervous system, and they are more conspicuous when the decrease in the serum sodium concentration is large or rapid (i.e., occurring within a period of hours).27 Headache, nausea, vomiting, muscle cramps, lethargy, restlessness, disorientation, and depressed reflexes can be observed. Whereas most patients with a serum sodium concentration exceeding 125 mmol per liter are asymptomatic, those with lower values may have symptoms, especially if the disorder has developed rapidly.4 Complications of severe and rapidly evolving hyponatremia include seizures, coma, permanent brain damage, respiratory arrest, brain-stem herniation, and death. These complications often occur with excessive water retention in patients who are essentially euvolemic (e.g., those recovering from surgery or those with primary polydipsia); menstruating women appear to be at particular risk.23,28
Hypotonic hyponatremia causes entry of water into the brain, resulting in cerebral edema (Figure 2Figure 2Effects of Hyponatremia on the Brain and Adaptive Responses.). Because the surrounding cranium limits expansion of the brain, intracranial hypertension develops, with a risk of brain injury. Fortunately, solutes leave brain tissues within hours, thereby inducing water loss and ameliorating brain swelling.29,30 This process of adaptation by the brain accounts for the relatively asymptomatic nature of even severe hyponatremia if it develops slowly. Nevertheless, brain adaptation is also the source of the risk of osmotic demyelination.31-33 Although rare, osmotic demyelination is serious and can develop one to several days after aggressive treatment of hyponatremia by any method, including water restriction alone.34-36 Shrinkage of the brain triggers demyelination of pontine and extrapontine neurons that can cause neurologic dysfunction, including quadriplegia, pseudobulbar palsy, seizures, coma, and even death. Hepatic failure, potassium depletion, and malnutrition increase the risk of this complication.1,37

 http://www.nejm.org/doi/pdf/10.1056/NEJM200005183422006