What are the clinical manifestations of hyponatremia?
Not all patients with hyponatremia will be symptomatic. While neurons are especially sensitive to osmotic stress, astrocyte-mediated expulsion of electrolytes into the extracellular fluid (ECF) over several hours followed by organic osmolytes (e.g., taurine and glutamate) over the ensuing 24 to 48 hours prevents intracellular swelling. Thus, patients who develop a serum sodium concentration between 125 and 135 mEq/L over greater than 48 hours will often have minimal or no symptoms. Observational studies, however, have demonstrated an association between even mild hyponatremia (serum sodium concentration 130 to 134 mEq/L) and increased in-hospital mortality, falls, and reduced bone density. Other studies have noted impaired motor function and gait even with modest reductions in serum sodium concentration. The combination of cognitive impairment, unsteady gait, increased falls, and osteoporosis constitute a “perfect storm” for development of bone fractures. An increase in fracture risk has indeed been documented. Rapid decreases in plasma sodium concentration (from >134 to <125 mEq/L within 48 hours) are faster than compensatory loss of intracellular solute, so the relatively hypertonic intracellular compartment osmotically absorbs water. This cellular swelling particularly affects the brain given the limit to expansion within a tightly encasing cranium. Thus, the manifestations of hyponatremia are predominantly neurologic and include nausea, vomiting, malaise, headache, lethargy, confusion, and muscle cramps. In severe cases, seizures, coma, tentorial herniation, and neurogenic pulmonary edema can occur.
