Allostasis and the Clinical Manifestations of Mild to Moderate Chronic Hyponatremia: No Good Adaptation Goes Unpunished

When homeostatic regulatory systems are unable to maintain a normal serum sodium concentration, the organism must adapt to demands of a disordered internal environment, a process known as “allostasis.” Human cells respond to osmotic stress created by an abnormal serum sodium level with the same adaptations used by invertebrate organisms that do not regulate body fluid osmolality. To avoid intolerable changes in their volume, cells export organic osmolytes when exposed to a low serum sodium concentration and accumulate these intracellular solutes when serum sodium concentration increases. The brain’s adaptation to severe hyponatremia (serum sodium < 120 mEq/L) has been studied extensively. However, adaptive responses occur with less severe hyponatremia and other tissues are affected; the consequences of these adaptations are incompletely understood. Recent epidemiologic studies have shown that mild (sodium, 130-135 mEq/L) and moderate (sodium, 121-129 mEq/L) chronic hyponatremia, long thought to be inconsequential, is associated with adverse outcomes. Adaptations of the heart, bone, brain, and (possibly) immune system to sustained mild to moderate hyponatremia may adversely affect their function and potentially the organism’s survival. This review explores what is known about the consequences of mild to moderate chronic hyponatremia and the potential benefits of treating this condition.