The word ascites is of Greek origin (askos) and means bag or sac. Ascites describes the condition of pathologic fluid collection within the abdominal cavity. Healthy men have little or no intraperitoneal fluid, but women may normally have as much as 20 mL, depending on the phase of their menstrual cycle. This article focuses only on ascites associated with cirrhosis.
See the image below.
View Image | This computed tomography scan demonstrates free intraperitoneal fluid due to urinary ascites. |
For patient education resources, see Digestive Disorders Center and Heart Health Center, as well as Cirrhosis, Hepatitis B (HBV, HepB), Hepatitis C, and Congestive Heart Failure.
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.[1]
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.
Ambulatory patients with an episode of cirrhotic ascites have a 3-year mortality rate of 50%. The development of refractory ascites carries a poor prognosis, with a 1-year survival rate of less than 50%.[2]
Healthy men have little or no intraperitoneal fluid, but women may normally have as much as 20 mL, depending on the phase of their menstrual cycle.
The prognosis for patients with ascites due to liver disease depends on the underlying disorder, the degree of reversibility of a given disease process, and the response to treatment.
The most important aspect of patient education is determining when therapy is failing and recognizing the need to see a physician. Unfortunately, in most cases, liver failure has a dismal prognosis. All patients must be taught which complications are potentially fatal and the signs and symptoms that precede them.
Abdominal distention and/or pain despite maximal diuretic therapy are common problems, and patients must realize the importance of seeing a physician immediately.
Patients with ascites often state that they have recently noticed an increase in their abdominal girth.
Because most cases of ascites are due to liver disease, patients with ascites should be asked about risk factors for liver disease. These include the following:
Patients with alcoholic liver disease who alternate between heavy alcohol consumption and abstention (or light consumption) may experience ascites in a cyclic fashion.
When a patient with a very long history of stable cirrhosis develops ascites, the possibility of superimposed hepatocellular carcinoma (HCC) should be considered.
Obesity, hypercholesterolemia, and type 2 diabetes mellitus are recognized causes of nonalcoholic steatohepatitis, which can progress to cirrhosis.
Patients with a history of cancer, especially gastrointestinal cancer, are at risk for malignant ascites. Malignancy-related ascites is frequently painful, whereas cirrhotic ascites is usually painless.
Patients who develop ascites in the setting of established diabetes or nephrotic syndrome may have nephrotic ascites.
The physical examination in a patient with ascites should focus on the signs of portal hypertension and chronic liver disease. Note the following:
Portal hypertension (serum-ascites albumin gradient [SAAG] >1.1 g/dL)
Hypoalbuminemia (SAAG <1.1 g/dL)
Miscellaneous conditions (SAAG <1.1 g/dL)
Infections
Malignant conditions
Other rare conditions
The most common complication of ascites is the development of spontaneous bacterial peritonitis (ascitic fluid with PMN count of >250 μ L). Note the following:
Complications of paracentesis include infection, electrolyte imbalances, bleeding, and bowel perforation. Bowel perforation should be considered in any patient with recent paracentesis who develops a new onset of fever and/or abdominal pain. All patients with long-standing ascites are at risk of developing umbilical hernias. Large-volume paracentesis often results in large intravascular fluid shifts. This can be avoided by administering albumin replacement if more than 5 L is removed.
Acute kidney injury in the setting of ascites and cirrhosis is a medical emergency, requiring prompt diagnosis and multimodal management.[5]
Abdominal ultrasonography, diagnostic paracentesis, and ascitic fluid cultures are recommended by the British Society of Gastroenterology, the European Association for the Study of the Liver (EASL), and the American Association for the Study of Liver Diseases (AASLD), particularly in the setting of supsected infection.[1]
Laparoscopy may be valuable for the diagnosis of otherwise unexplained cases, especially if malignant ascites is suspected.[6] This may be of particular importance in the diagnosis of malignant mesothelioma.
In patients with new-onset ascites of unknown origin, peritoneal fluid should be sent for cell count, albumin level, culture, total protein, Gram stain, and cytology. Note the following:
Elevation of the diaphragm, with or without sympathetic pleural effusions (hepatic hydrothorax), is visible in the presence of massive ascites. More than 500 mL of fluid is usually required for ascites to be diagnosed based on findings from abdominal films.
Many nonspecific signs suggest ascites, such as diffuse abdominal haziness, bulging of the flanks, indistinct psoas margins, poor definition of the intra-abdominal organs, erect position density increase, separation of small bowel loops, and centralization of floating gas containing small bowel.
The direct signs are more reliable and specific. In 80% of patients with ascites, the lateral liver edge is medially displaced from the thoracoabdominal wall (Hellmer sign). In the pelvis, fluid accumulates in the rectovesical pouch and then spills into the paravesical fossa. The fluid produces symmetric densities on both sides of the bladder, which is termed a "dog's ear" or "Mickey Mouse" appearance. Medial displacement of the cecum and ascending colon and lateral displacement of the properitoneal fat line are present in more than 90% of patients with significant ascites. Although obliteration of the hepatic angle as been suggested as a sign of increased intra-abdominal fluid, this finding is seen in 80% of healthy patients.
Real-time ultrasonography is the easiest and most sensitive technique for the detection of ascitic fluid. Volumes as small as 5-10 mL can routinely be visualized. Uncomplicated ascites appears as a homogeneous, freely mobile, anechoic collection in the peritoneal cavity that demonstrates deep acoustic enhancement. Free ascites does not displace organs but typically situates itself between them, contouring to organ margins and demonstrating acute angles at the point at which the fluid borders the organ.
The smallest amounts of fluid tend to collect in the Morison pouch (posterior subhepatic space) and around the liver as a sonolucent band. With massive ascites, the small bowel loops have a characteristic polycyclic, "lollipop," or arcuate appearance because they are arrayed on either side of the vertically floating mesentery.
Certain ultrasonographic findings suggest that the ascites may be infected, inflammatory, or malignant. These findings include coarse internal echoes (blood), fine internal echoes (chyle), multiple septa (tuberculous peritonitis, pseudomyxoma peritonei), loculation or atypical fluid distribution, matting or clumping of bowel loops, and thickening of interfaces between fluid and adjacent structures. In malignant ascites, the bowel loops do not float freely but may be tethered along the posterior abdominal wall, plastered to the liver or other organs, or surrounded by loculated fluid collections.
Most patients (95%) with carcinomatous peritonitis have a gallbladder wall that is less than 3 mm thick. Mural thickening of the gallbladder is associated with benign ascites in 82% of cases. The thickening of the gallbladder is primarily a reflection of cirrhosis and portal hypertension.
Ascites is demonstrated well on CT scan images. Small amounts of ascitic fluid localize in the right perihepatic space, the posterior subhepatic space, and the Douglas pouch (rectouterine pouch). See the image below.
View Image | This computed tomography scan demonstrates free intraperitoneal fluid due to urinary ascites. |
A number of CT scan features suggest neoplasia. Hepatic, adrenal, splenic, or lymph node lesions associated with masses arising from the gut, ovary, or pancreas are suggestive of malignant ascites. Patients with malignant ascites tend to have proportional fluid collections in the greater and lesser sacs; whereas, in patients with benign ascites, the fluid is observed primarily in the greater sac and not in the lesser omental bursae.
Abdominal paracentesis: Abdominal paracentesis is the most rapid and perhaps the most cost-effective method of diagnosing the cause of ascites formation. Guidelines from the American Association for the Study of Liver Diseases (AASLD) for management of adult patients with ascites due to cirrhosis advocate paracentesis in all patients with clinically apparent new-onset ascites (class I, level C recommendation).[8]
Bleeding from paracentesis is sufficiently uncommon that the AASLD does not recommend the prophylactic use of fresh frozen plasma or platelets beforehand (class III, level C recommendation).[8]
For more detailed information regarding paracentesis, including images and video, please see the Medscape article Paracentesis [in the Clinical Procedures section].
Ascites may be semi-quantified using the following system:
Sodium restriction (20-30 mEq/d) and diuretic therapy constitute the standard medical management for ascites and are effective in approximately 95% of patients. Note the following:
In a systematic review and meta-analysis of 10 trials comprising 462 patients with cirrhotic ascites, Guo et al reported that midodrine, a vasopressor, used as a novel threapy for the ascites caused by cirrhosis did not improve survival but potentially improved response rates and reduced plasma renin activity.[18] However, when midodrine was used as an alternative to albumin in large-volume paracentesis, the mortality was higher for those receiving midodrine than for those receiving albumin;midodrine and albumin had a similar association with the development paracentesis-induced circulatory dysfunction.[18]
Conservative management appears to be the treatment of choice for patients with chylous ascites.[3]
Patients can actually be maintained free of ascites if sodium intake is limited to 10 mmol/d. However, this is not practical outside a metabolic ward.
Twenty-four–hour urinary sodium measurements are useful in patients with ascites related to portal hypertension in order to assess the degree of sodium avidity, monitor the response to diuretics, and assess compliance with diet.
For grade 3 or 4 ascites, therapeutic paracentesis may be necessary intermittently.
The peritoneovenous shunt is an alternative for patients with medically intractable ascites (see image below).
View Image | Peritoneovenous shunt. |
This is a megalymphatic shunt that returns the ascitic fluid to the central venous system. Beneficial effects of these shunts include increased cardiac output, renal blood flow, glomerular filtration rate, urinary volume, and sodium excretion and decreased plasma renin activity and plasma aldosterone concentration. Although it has largely been supplanted by TIPS, peritoneovenous shunting has been shown to improve short-term survival (compared with paracentesis) in cancer patients with refractory malignant ascites.[19] The AASLD suggests considering peritoneovenous shunting for patients with refractory ascites who are not candidates for paracentesis, transplant, or TIPS (class I, level A recommendation).[8]
The AASLD recommends that patients with cirrhosis and ascites be considered for liver transplantation (class I, level B recommendation).[8]
Consultation with a gastrointestinal specialist and/or hepatologist should be considered for all patients with ascites, particularly if the ascites is refractory to medical treatment.
Sodium restriction of 500 mg/d (22 mmol/d) is feasible in a hospital setting; however, it is unrealistic in most outpatient settings. A more appropriate sodium restriction is 2000 mg/d (88 mmol). Indiscriminate fluid restriction is inappropriate. Fluids need not be restricted unless the serum sodium level drops below 120 mmol/L.
The best method of assessing the effectiveness of diuretic therapy is by monitoring body weight and urinary sodium levels.
In general, the goal of diuretic treatment of ascites should be to achieve a weight loss of 300-500 g/d in patients without edema and 800-1000 g/d in patients with edema.
Once ascites has disappeared, diuretic treatment should be adjusted to maintain the patient free of ascites.
The goals of pharmacotherapy are to reduce morbidity and to prevent complications in patients with ascites.
Diuretics should be initiated in patients whose ascites does not respond to sodium restriction. A useful regimen is to start with spironolactone at 100 mg/d. The addition of loop diuretics may be necessary in some cases to increase the natriuretic effect. If no response occurs after 4-5 days, the dosage may be increased stepwise up to spironolactone at 400 mg/d plus furosemide at 160 mg/d.
Clinical Context: For the management of edema resulting from excessive aldosterone excretion. Competes with aldosterone for receptor sites in distal renal tubules, increasing water excretion while retaining potassium and hydrogen ions. The peak effect of Aldactone is approximately 3 d.
Clinical Context: Increases the excretion of water by interfering with chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule. Dose must be individualized to patient.
Depending on the response, administer at increments of 20-40 mg, no sooner than 6-8 h after the previous dose, until the desired diuresis occurs. When treating infants, titrate in increments of 1 mg/kg/dose until a satisfactory effect is achieved.
Clinical Context: A pyrazine-carbonyl-guanidine unrelated chemically to other known antikaliuretic or diuretic agents. Potassium-conserving (antikaliuretic) drug which, compared with thiazide diuretics, possesses weak natriuretic, diuretic, and antihypertensive activity.
Clinical Context: Helps treat edema in congestive heart failure. Increases excretion of sodium, water, potassium, and hydrogen ions by inhibiting reabsorption of sodium in distal tubules. May be more effective in those with impaired renal function.
Clinical Context: Inhibits tubular reabsorption of electrolytes by increasing the osmotic pressure of glomerular filtrate. Increases urinary output.