Hyponatremia in cirrhosis: pathophysiology and management.

Abstract

Hyponatremia is frequently seen in patients with ascites secondary to advanced cirrhosis and portal hypertension. The development of ascites in patients with cirrhosis is multi-factorial. Portal hypertension and the associated systemic vasodilation lead to activation of the sodium-retaining neurohumoral mechanisms which include the renin-angiotensin-aldosterone system, sympathetic nervous system and antidiuretic hormone (ADH). The net effect is the avid retention of sodium and water to compensate for the low effective circulatory volume resulting in the development of ascites. Although not apparent in the early stages of cirrhosis, the progression of cirrhosis and ascites leads to impairment of the kidneys to eliminate solute- free water. This leads to additional compensatory mechanisms including non-osmotic secretion of ADH, also known as arginine vasopressin, further worsening excess water retention and thereby hyponatremia. Hyponatremia is associated with increased morbidity and mortality in patients with cirrhosis, and is an important prognostic marker both before and after liver transplant. The management of hyponatremia in this setting is a challenge as conventional therapy for hyponatremia including fluid restriction and loop diuretics are frequently inefficacious. In this review, we discuss the pathophysiology and various treatment modalities, including selective vasopressin receptor antagonists, for the management of hyponatremia in patients with cirrhosis.