General Considerations

The major causes of ascites are listed in Table 46–1. In North America and Europe, 90% of the cases of ascites are due to cirrhosis, malignancy, and congestive heart failure. In Europe and other countries tuberculous peritonitis is not uncommon. Ascites is a cardinal manifestation of decompensated cirrhosis of the liver. Approximately 50% of patients with cirrhosis will develop ascites within 10 years. The development of ascites in patients with cirrhosis provides important prognostic information as up to 50% of such patients will die within 5 years.

Pathogenesis

A. Development of Cirrhotogenic Ascites

Five major factors are involved in the pathogenesis of cirrhotogenic ascites: portal hypertension, hypoalbuminemia, sodium retention, water retention, and increased lymph formation.

Portal hypertension is universally present in patients with ascites secondary to cirrhosis of the liver. Two major mechanisms contribute to the development of portal hypertension: (1) distortion of the hepatic vascular architecture caused by reduction in the intrahepatic arterial bed as a result of fibrosis and nodule formation, and (2) increased production of vasodilatory substances, most importantly nitric oxide synthase.

Hypoalbuminemia results from decreased albumin synthesis that, in turn, is secondary to impaired hepatocellular synthetic function. It should be emphasized that there is no critical level of serum albumin at which ascites formation takes place. In one large series of cirrhotic patients with ascites, serum albumin levels ranged from 2.3 g% to 3.8 g%.

Increased sodium retention appears to be related primarily to abnormalities of proximal tubular function, and increased proximal tubular reabsorption of sodium. The latter occurs due to increased aldosterone secretion in response to changes in effective circulating blood volume. Activation of the renin-angiotensin-aldosterone system contributes to abnormal sodium retention.

It has long been appreciated that cirrhotic patients have an impaired ability to excrete a water load. A major factor in the abnormal water retention is abnormal delivery of sodium in the distal tubule with a consequent inability to generate free water. This is augmented by increased vasopressin secretion (antidiuretic hormone [ADH]) in response to a decreased effective circulating blood volume.

Increased lymph formation occurs in the liver and splanchnic circulation.

B. Hormone Alterations

Table 46–2 lists key hormone alterations in cirrhotogenic ascites. In decompensated cirrhosis, serum levels of renin, aldosterone, ADH, and norepinephrine are all increased. In patients who respond to diuretic therapy, there is normalization of these levels. However, in patients with refractory ascites, despite expansion of intravascular volume, serum renin, ADH, aldosterone, and norepinephrine remain inappropriately elevated.

Circulatory dysfunction is important in cirrhotogenic ascites. Initially, plasma volume, cardiac output, and heart rate increase because the splanchnic circulation behaves functionally as a large arteriovenous fistula. With progression of liver disease, portal pressure increases further, as does splanchnic vasodilation. There is increased sodium retention and ascites formation. The renin-angiotensin-aldosterone system and sympathetic nervous system become activated in parallel with intense reduction in urinary sodium excretion to values of less than 10 mEq/24 h. Increased secretion of ADH occurs at later stages, which explains why hyponatremia is a later event in decompensated cirrhosis.

C. Decreased Effective Circulating Blood Volume

Table 46–3 contrasts changes in mean arterial pressure, plasma volume, cardiac index, plasma renin level, and norepinephrine level in cirrhotic patients with and without hepatorenal syndrome with values in healthy individuals. In patients with cirrhosis and ascites, plasma volume is increased 50% above normal; additionally, the cardiac index is increased as are plasma renin and norepinephrine levels. In patients with hepatorenal syndrome, similar changes persist despite intravascular volume repletion.

The key factors leading to the development of cirrhotogenic ascites are summarized later. Cirrhosis gives rise to portal hypertension, which results in splanchnic arterial vasodilation. Splanchnic arterial vasodilation then leads to a decreased effective arterial circulating blood volume and activation of the renin-angiotensin and sympathetic nervous systems, which, in turn, results in renal vasoconstriction and sodium retention. The splanchnic vasodilation causes increased capillary pressure and permeability that contribute to ascites. Splanchnic arterial vasodilation also results in increased venous return and increased cardiac output as it acts as an arteriovenous fistula. This, in turn, can result in pulmonary vasodilation and infrequently results in the hepatopulmonary syndrome.

Although circulating blood volume is increased in cirrhotogenic ascites, the effective blood volume (ie, the fraction present within the intrathoracic circulation that is able to influence baroreceptors, the sympathetic nervous system, and the renin-angiotensin system [ADH]) is actually reduced. This mechanism promotes sodium and water retention. A large volume of blood enters and leaves the portal venous system rapidly due to decreased splanchnic resistance. The hyperdynamic circulation leads to vasodilation of the pulmonary circulation to allow increased venous return. Increased venous return and arterial hypertension of the systemic circulation lead to increased blood volume, tachycardia, and increased cardiac output, as summarized in Table 46–3.

Clinical Findings

A. Symptoms and Signs

Patients with decompensated cirrhosis and ascites often exhibit peripheral stigmata of chronic parenchymal liver disease. These include spider angiomata, palmar erythema, gynecomastia, parotid enlargement, Dupuytren contracture, paucity of axillary and pubic hair, and testicular atrophy, with the north-south testicular diameter being less than 3 cm. The triad of findings of parotid enlargement, gynecomastia, and Dupuytren contracture usually implies an alcoholic etiology leading to the patient’s cirrhosis. The triad of findings of hepatomegaly, ascites, and increased venous collateral of the anterior abdominal walls always indicates the presence of portal hypertension.

A diagnosis of cirrhosis can be made on the basis of two physical findings and two laboratory findings. The two physical findings are asterixis and ascites; the two laboratory findings are hypoalbuminemia (serum albumin levels <2.8 g/dL) and prolongation of the prothrombin time (international normalized ratio [INR] >1.6). The presence of “classical” physical findings (eg, bulging flanks, shifting dullness, and a fluid wave), however, is only about 60–70% accurate in predicting the presence of ascites.

B. Laboratory Findings

Patients with ascites should always be evaluated with diagnostic paracentesis to determine the cause. The most useful parameter to classify ascites is the SAAG, which is calculated by subtracting the ascites albumin concentration from the serum value. With approximately 98% accuracy a difference of greater than 1.1 g/dL is consistent with ascites secondary to portal hypertension. Conversely, gradients less than 1.1 g/dL are associated with ascites due to inflammation, infection, malignancy, and disorders such as pancreatogenous ascites, tuberculous peritonitis with ascites. Thus, the underlying cause can be readily differentiated.

In patients with cirrhotogenic ascites, measurement of urine electrolytes is important. If ascites is due to cirrhosis, urine sodium excretion will be low (eg, frequently <10 mEq/24 h) and potassium excretion increased to a value of greater than 30 mEq/24 h. This can also be used as a baseline measurement to determine the effectiveness of diuretic therapy as distal-acting agents such as spironolactone frequently cause a reversal of the abnormal sodium-potassium ratio. In addition, if patients with cirrhotogenic ascites are found to have high urine sodium excretion it would suggest another complicating factor such as malignancy.