Pathogenesis of water and sodium retention in cirrhosis

The pathogenesis of renal sodium and water retention in cirrhosis involves extrarenal mechanisms because when kidneys from cirrhotic patients are transplanted into persons with normal livers, renal sodium and water retention no longer occurs. Cirrhosis is accompanied by portal hypertension, which leads to a hyperdynamic circulatory state. The Peripheral Arterial Vasodilation Hypothesis incriminates a relative underfilling of the arterial vascular compartment, which leads to the same neurohumoral responses that occurs in low cardiac output. Activation of the renain-angiotensin-aldosterone axis and the sympathetic system as well as non-osmotic release of vasopressin are well documented in cirrhosis. This sequence of events results in renal water and sodium retention, failure to escape from the sodium-retaining effect of aldosterone, and renal resistance to atrial natriuretic peptide. Dilutional hyponatremia is the strongest predictor of the occurrence of hepatorenal syndrome. The pathogenesis of the peripheral arterial vasodilation is not completely elucidated, but there is evidence for a major role of nitric oxide (NO). Increased vascular NO production has been demonstrated in cirrhosis. In the rat model of cirrhosis, normalization of vascular NO production with a NOS inhibitor corrects the hyperdynamic circulation, improves sodium and water excretion, and decreases neurohumoral activation. This insight into the mechanism(s) of the peripheral arterial vasodilation in cirrhosis should provide new tools in the treatment of edema and ascites, a major cause of morbidity and mortality in cirrhosis.