Hiponatremia

PRIMARY CARE

Review Article

Primary Care

H YPONATREMIA
AND

HORACIO J. ADROGUÉ, M.D., NICOLAOS E. MADIAS, M.D.

YPONATREMIA 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 tothe 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 andhypotonicity (Fig. 1B, 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 (Fig. 1C). Importantly, patients who have hypotonichyponatremia 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 inthe extracellular compartment (as occurs with hyperglycemia or retention of hypertonic mannitol); serum osmolality is increased, as is tonicity, the latter causing dehydration of cells (Fig. 1D). Re-

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tention 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 ofwater. 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 thislaboratory 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

From the Department ofMedicine, Baylor College of Medicine and Methodist Hospital, and the Renal Section, Department of Veterans Affairs Medical Center, Houston (H.J.A.); and the Department of Medicine, Tufts University School of Medicine, and the Division of Nephrology and Tupper Research Institute, New England Medical Center, Boston (N.E.M.). Address reprint requests to Dr. Madias at the Division of Nephrology, NewEngland Medical Center, Box 172, 750 Washington St., Boston, MA 02111, or at nmadias@infonet.tufts.edu. ©2000, Massachusetts Medical Society.

Hypotonic (dilutional) hyponatremia represents an excess of water in relation to existing sodium stores, which can be decreased, essentially normal, or increased (Fig. 1). Retention of water most commonly reflects the presence of conditions that impair renalexcretion 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 1).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...