The accumulation of ascitic fluid represents a state of total-body sodium and water excess, but the event that initiates the unbalance is unclear. Although many pathogenic processes have been implicated in the development of abdominal ascites, about 75% likely occur as a result of portal hypertension in the setting of liver cirrhosis, with the remainder due to infective, inflammatory, and infiltrative conditions. Three theories of ascites formation have been proposed: underfilling, overflow, and peripheral arterial vasodilation.
The underfilling theory suggests that the primary abnormality is inappropriate sequestration of fluid within the splanchnic vascular bed due to portal hypertension and a consequent decrease in effective circulating blood volume. This activates the plasma renin, aldosterone, and sympathetic nervous system, resulting in renal sodium and water retention.
The overflow theory suggests that the primary abnormality is inappropriate renal retention of sodium and water in the absence of volume depletion. This theory was developed in accordance with the observation that patients with cirrhosis have intravascular hypervolemia rather than hypovolemia.
The most recent theory, the peripheral arterial vasodilation hypothesis, includes components of both of the other theories. It suggests that portal hypertension leads to vasodilation, which causes decreased effective arterial blood volume. As the natural history of the disease progresses, neurohumoral excitation increases, more renal sodium is retained, and plasma volume expands. This leads to overflow of fluid into the peritoneal cavity. The vasodilation theory proposes that underfilling is operative early and overflow is operative late in the natural history of cirrhosis.
Although the sequence of events that occurs between the development of portal hypertension and renal sodium retention is not entirely clear, portal hypertension apparently leads to an increase in nitric oxide levels. Nitric oxide mediates splanchnic and peripheral vasodilation. Hepatic artery nitric oxide synthase activity is greater in patients with ascites than in those without ascites.
Regardless of the initiating event, a number of factors contribute to the accumulation of fluid in the abdominal cavity. Elevated levels of epinephrine and norepinephrine are well-documented factors. Hypoalbuminemia and reduced plasma oncotic pressure favor the extravasation of fluid from the plasma to the peritoneal fluid, and, thus, ascites is infrequent in patients with cirrhosis unless both portal hypertension and hypoalbuminemia are present.