Ascites is a detectable collection of free fluid in the peritoneal cavity. Ascitic fluid is derived from the vascular compartment subserving the hepatosplanchnic viscera. Two factors are important in the formation of ascites: an increased total body sodium and water, and increased sinusoidal portal pressure. In cirrhosis, hepatic dysfunction and sinusoidal portal pressure probably both send a message to the kidney to retain excess sodium and fluid, while the portal hypertension serves to localize excess fluid to the peritoneal cavity rather than the periphery. Portal hypertension alone without hepatic dysfunction rarely results in ascites.

The pathogenesis of ascites formation remains controversial. The "underfill" theory proposes that ascites occurs as a primary event. Sequestration of fluid into the peritoneal cavity as a result of changes in Starling's forces within the splanchnic circulation results in a reduction of the circulatory volume. This in turn leads to stimulation of the sympathetic nervous and renin-angiotensin-aldosterone systems, which promote renal sodium and water retention. The "overflow theory," on the other hand, proposes that renal sodium retention occurs as a primary event. This may be due to the increased production of a sodium-retaining factor or the reduced synthesis of a natriuretic factor by the diseased liver. The circulatory volume is expanded. In the presence of abnormal Starling's forces in the splanchnic circulation, the retained fluid is preferentially localized to the peritoneal cavity as ascites. More recently, "the peripheral arterial vasodilation hypothesis," which encompasses features of both the underfill and overflow theories, was put forward. It proposes that in cirrhosis, arterial vasodilation leads to a decrease in splanchnic and systemic vascular resistance with pooling of blood in the splanchnic circulation, leading to a reduction in the effective arterial blood volume. This in turn activates neurohumoral pressor systems, promoting renal sodium and water retention in an attempt to restore the effective arterial blood volume and maintain blood pressure. When increased renal sodium reabsorption cannot compensate for the arterial vasodilation, arterial underfilling occurs. Then the cascade of further activation of various neurohumoral pressor systems leading to increased sodium retention begins, and ultimately ascites is formed (Figure 13).

Arterial vasodilation is also responsible for the hyperdynamic circulation that is often evident in cirrhosis. This clinically manifests as an increased cardiac output, bounding pulse, wide pulse pressure and systemic hypotension. Locally produced vasodilators may be responsible. More recently, it has been proposed that chronic endotoxemia associated with cirrhosis may stimulate the synthesis and release of a potent endothelin-derived relaxing factor, nitric oxide, resulting in splanchnic and systemic vasodilation.

Clinically, the first evidence of ascites is an increase in abdominal girth accompanied by weight gain. Peritoneal fluid of less than 2 L is difficult to detect clinically, and ultrasound is useful in defining small amounts of ascites. The patient is sallow and intravascularly depleted. Muscle wasting is profound. The abdomen is distended, often with fullness in the flanks and an everted umbilicus. Scrotal edema is frequent. Distended abdominal wall veins that radiate from the umbilicus represent the presence of portal-systemic collaterals. The earliest sign of ascites is dullness to percussion in the flanks. Shifting dullness and a fluid thrill mean that more fluid is present.

A pleural effusion is found in a small percentage of patients with ascites, usually on the right side. This is due to the presence of a diaphragmatic defect that allows ascitic fluid to pass into the pleural cavity.

Examination of ascitic fluid by diagnostic paracentesis should be performed at first presentation, or when there is alteration of the patient's clinical state, such as a sudden increase in the amount of ascitic fluid, worsening of encephalopathy or presence of fever. The purpose of the examination is to rule out other complications such as spontaneous bacterial peritonitis, tuberculosis and hepatocellular carcinoma. Ascitic fluid analysis should include a total polymorph count, protein and albumin concentrations and direct inoculation of at least 10 mL of ascitic fluid each into blood culture bottles at the bedside, as this increases the positive culture yield. A serum-ascitic fluid albumin gradient of greater than 11 g/L represents cirrhotic rather than malignant ascites. A high protein content may be associated with the Budd-Chiari syndrome or seen in pancreatic ascites. A total polymorph count of greater than 250/µL is diagnostic of spontaneous bacterial peritonitis.

Although bed rest will result in a redistribution of body fluid, fluid and salt restriction is required to mobilize the ascites. The patient is usually prescribed a no-added-salt diet containing 2 g (100 mmol) sodium/day, and monitored carefully with daily weights. Measurement of abdominal girth is unreliable, as gaseous distention is common. Too rapid mobilization of fluid will result in worsening of renal function; one should aim at a weight loss of 0.5 kg/day. Patients with peripheral edema can have their fluid mobilized more rapidly, as the edema fluid can easily be absorbed to replenish the intravascular volume.

Diuretic therapy is usually required in addition to salt and fluid restriction. The potassium-sparing diuretic spironolactone can be given in a single daily dose, starting at a dose of 100 mg/day, and may be increased by 100 mg per week up to 400 mg/day if the response is inadequate. Spironolactone has a slow onset of action, and therefore frequent dose adjustments are unnecessary. Its half-life in cirrhotic patients can be as long as 10 days; therefore, it also has a slow offset of action and patients should still be monitored after spironolactone is discontinued. One of its unacceptable side effects is painful gynecomastia. Other potassium-sparing diuretics, such as amiloride and triamterene, are less potent but acceptable alternatives. If there is no diuretic response and the patient is compliant with the sodium intake, a loop diuretic such as furosemide is added. Electrolyte abnormalities are common with diuretic therapy and should be monitored regularly. Hypokalemia and hypochloremic alkalosis can precipitate encephalopathy. Too rapid diuresis can lead to azotemia and the hepatorenal syndrome.

Refractory ascites is defined as ascites unresponsive to 400 mg of spironolactone or 30 mg of amiloride plus up to 120 mg of furosemide daily for two weeks. Noncompliance with sodium restriction is a major and often overlooked cause of resistant ascites, and careful questioning of the patient and the patient's relatives is often required to confirm this. Other causes of resistant ascites include the development of spontaneous bacterial peritonitis, hepatocellular carcinoma and intrinsic renal pathology. Refractory ascites without any underlying cause usually indicates advanced cirrhosis associated with a grave prognosis, with only a 50% survival at two years. Large-volume paracentesis is now recognized as a safe and effective therapy for the treatment of refractory ascites. Removal of ascitic fluid volume of up to 5 L without the simultaneous infusion of plasma expanders such as concentrated albumin is safe in non-edematous patients. Larger volumes can be removed in edematous patients. However, repeated paracenteses may not be practical for all patients with refractory ascites, and a peritoneovenous (LeVeen) shunt should be considered in selected patients with good liver reserve. It may be dramatically effective in resolving the ascites, but in patients with decompensated liver disease it is followed by higher morbidity and mortality. Previous abdominal surgery, spontaneous bacterial peritonitis and large varices are relative contraindications to the procedure. Early complications include pulmonary edema and disseminated intravascular coagulopathy. Late complications include thrombosis of the superior vena cava, infection and blockage or dislodgement of the shunt, all of which require its immediate removal. In suitable patients, the LeVeen shunt, in addition to improved management of ascites, can significantly enhance well-being and nutritional status. More recently, a transjugular intrahepatic portal-systemic shunt (TIPS) has been shown to be an effective means of managing refractory ascites. This method involves creating a communication between a branch of the hepatic vein and a branch of the portal vein held open by a metal stent. Liver transplantation should always be considered as a treatment option in these patients.

Spontaneous bacterial peritonitis (SBP) is a common and often fatal complication of cirrhosis. In this clinical syndrome, ascites becomes infected in the absence of a recognizable cause of peritonitis. Its increased incidence over the past decade may be due to greater recognition. It is particularly frequent if the patient has severely decompensated cirrhosis with jaundice. In most cases, the infection occurs after admission into hospital. About one-third of cases of SBP are asymptomatic; therefore, the clinician should not hesitate in performing a diagnostic paracentesis. Typically, it presents with fever and/or abdominal pain. It may also present atypically, solely as a worsening of the encephalopathy or renal dysfunction. Diagnosis of SBP is made by paracentesis. Positive culture results may take 48 hours and Gram's stains of ascitic fluid are positive in only 10-50% of infected patients. The "gold standard" for diagnosis of SBP is a polymorphonuclear (PMN) count of >250 cells/µL. A variant of SBP known as culture-negative neutrocytic ascites occurs as culture-negative cases of suspected SBP with an ascitic fluid PMN count of >250 cells/µL. The patients with culture-negative neutrocytic ascites have the same clinical presentation and carry the same unfavorable prognosis as those with SBP. Therefore, treatment for suspected SBP should start immediately after the diagnostic PMN count rather than waiting for positive culture results. Gram-negative bacilli account for 70% of cases of SBP. E. coli is the most common pathogen isolated. Other gram-negative organisms include Klebsiella species, Citrobacter freundii, Proteus and Enterobacter. Gram-positive organisms are responsible for 25% of cases; these include Streptococcus pneumoniae, Streptococcus viridans, group D streptococci and Staphylococcus aureus. Anaerobic organisms are uncommon causes of SBP, as the oxygen tension in the ascitic fluid is too high for their survival. Among these, Bacteroides species appear to be more common than other anaerobes. Cefotaxime, a broad-spectrum, third-generation cephalosporin, is now recognized as the treatment of choice for SBP. Its spectrum includes most organisms responsible for SBP and it is not nephrotoxic in the therapeutic range. A 5-day course of cefotaxime 2 g IV every 8 hours has been shown to be as effective as a 10-day course. The ascitic fluid PMN count should decrease rapidly, normalizing within 48 hours in response to treatment together with a parallel clinical improvement. Aminoglycosides should not be used since cirrhotic patients are particularly sensitive to their nephrotoxic effects, and monitoring serum levels of aminoglycosides is no guarantee against aminoglycoside-induced nephrotoxicity.

Secondary bacterial peritonitis should be considered as a differential diagnosis if the following features are present: (1) multiple organisms are grown from the ascitic fluid; (2) ascitic fluid protein concentration >l g/dL; or (3) PMN count remains high despite antibiotic therapy (Table 19).

Radiographic examinations are required to exclude perforation of the gastrointestinal tract, with emergency surgery only where perforation is confirmed. Despite successful treatment of SBP, the prognosis of these patients remains poor. SBP recurs frequently in cirrhotic patients. Selective intestinal decontamination to eliminate aerobic gram-negative bacilli with oral nonabsorbable antibiotics has proved effective in reducing the recurrence of SBP. Norfloxacin 400 mg daily has the advantages of rarely causing bacterial resistance and having a low incidence of side effects when administered chronically. The less expensive drug trimethoprim-sulfamethoxazole may be as effective for prophylaxis as norfloxacin. Despite decreased SBP recurrence rates with prophylactic antibiotics, no change in mortality has been demonstrated as yet. All patients who have experienced one episode of SBP should be considered for liver transplantation.