Etiology, diagnostics and therapy of hyponatremias

Abstract

Etiopathogenesis, diagnostics and therapy of hyponatremias are summarized for clinicians. Hyponatremia is the most common electrolyte abnormality. Mild to moderate hyponatremia and severe hyponatremia are found in 15-30% and 1-4% of hospitalized patients, respectively. Pathophysiologically, hyponatremias are classified into two groups: hyponatremia due to non-osmotic hypersecretion of vasopressin (hypovolemic, hypervolemic, euvolemic) and hyponatremia of non-hypervasopressinemic origin (pseudohyponatremia, water intoxication, cerebral salt wasting syndrome). Patients with mild hyponatremia are almost always asymptomatic. Severe hyponatremia is usually associated with central nervous system symptoms and can be life-threatening. Diagnostic evaluation of patients with hyponatremia is directed toward identifying the extracellular fluid volume status, the neurological symptoms and signs, the severity and duration of hyponatremia, the rate at which hyponatremia developed. The first step to determine the probable cause of hyponatremia is the differentiation of the hypervasopressinemic and non-hypervasopressinemic hyponatremias with measurement of plasma osmolality, glucose, lipids and proteins. For further differential diagnosis of hyponatremia, the determination of urine osmolality, the clinical assessment of extracellular fluid volume status and the measurement of urine sodium concentration provide important information. The most important representative of euvolemic hyponatremias is SIADH. The diagnosis of SIADH is based on the exclusion of other hyponatremic conditions; low plasma osmolality (<275 mosmol/kg) and inappropriate urine concentration (urine osmolality >100 mosmol/kg) are of pathognomic value. Acute (<48 hrs) severe hyponatremia (<120 mmol/l) necessitates emergency care with rapid restoration of normal osmotic milieu (1 mmol/l/hr increase rate of serum sodium). Patients with chronic symptomatic hyponatremia have a high risk of osmotic demyelination syndrome in brain if rapid correction of the plasma sodium occurs (maximal rate of correction of serum sodium should be 0.5 mmol/l/hr or less). The conventional treatments for chronic asymptomatic hyponatremia (except hypovolemic patients) include water restriction and/or the use of demeclocycline or lithium or furosemide and salt supplementation. Vasopressin receptor antagonists have opened a new forthcoming therapeutic era. V2 receptor antagonists, such as lixivaptan, tolvaptan, satavaptan and the V2+V1A receptor antagonist conivaptan promote the electrolyte-sparing excretion of free water and lead to increased serum sodium.