Biliary tract disease

Aetiology, genetics, pathogenesis and pathology

Most biliary pathology is secondary to gallstones. Eighty percent of gallstones in the Western world are composed primarily of cholesterol, but stones may also be formed from bile pigment (due to haemolysis) or may be of mixed origin. These components precipitate out to form crystals when bile is concentrated in the gallbladder. The crystals, if trapped in the gallbladder mucus, can grow, producing gallbladder sludge and then stones. Infection can play a role in the precipitation of stones, with bacteria—long dead—often found inside gallstones, as is explicit in the well-known aphorism of Lord Moynihan: ‘A gallstone is a tomb stone erected to the memory of organisms that lie dead with in them’. Symptoms occur when the gallbladder contracts, often after a meal, resulting in occlusion of the cystic duct by a stone and causing visceral pain (biliary colic). On relaxation of the gallbladder, the stone falls back into the gallbladder and symptoms subside. More prolonged gallbladder outlet obstruction leads to acute cholecystitis. Gallbladder distension and increased intraluminal pressure lead to inflammation, ischaemia and subsequent necrosis of the mucosal wall. Infection is not thought to play an initial part in the development of acute cholecystitis, but secondary infection may occur in up to 50% of cases. The main difference between acute cholecystitis and biliary colic is the inflammatory component, leading to ongoing pain, fever, localized peritonism and an elevated white cell count (WCC). Secondary bacterial infection is usually caused by aerobic bowel flora (such as Escherichia coli , Klebsiella species and, less commonly, Enterococcus faecalis ). Anaerobes are found infrequently, usually in the presence of obstruction.

Cholangitis requires the presence of two factors: biliary obstruction and infection.

Epidemiology

Around 10% to 15% of Western adults have gallstones (cholelithiasis). Stones are less common in African and Asian populations. In young adults, four times more females are affected than males, but the disparity narrows with age. The lifetime risk of gallstones is 35% in women and 20% in men. In women, the risk is increased further during and after pregnancy and with oral contraceptive use. This is likely due to endogenous sex hormones that enhance cholesterol secretion and increase bile cholesterol saturation.

Other risk factors for the development of gallstones include increasing age, diabetes, obesity, rapid weight loss, drugs (most notably exogenous oestrogens, octreotide, clofibrate and ceftriaxone), genetic predisposition, diseases of the terminal ileum and abnormal lipid profile.

Two-thirds of gallstones are asymptomatic. Gallstones may be present for decades before symptoms develop. Asymptomatic patients become symptomatic at a rate of 1% to 4% per year, but the risk decreases with time. Risk factors for stones becoming symptomatic are smoking, pregnancy and obesity. Stones may cause acute or chronic cholecystitis, acute biliary pain (biliary colic), pancreatitis or obstructive jaundice.

Biliary colic is the most common presentation (56%), followed by acute cholecystitis (36%), obstructive pancreatitis and cholangitis. Less common presentations include empyema, perforation, fistula formation, gallstone ileus, hydrops or mucocele of the gallbladder and carcinoma of the gallbladder.

Prevention

Many of the risk factors for gallstones, such as age and gender, are fixed. There is limited evidence to support preventive strategies, but maintaining a healthy weight and following a low-fat, high-fibre diet may reduce the risk. Patients on long-term statins also appear to be protected from gallstones. Ursodeoxycholic acid is useful in preventing high-risk patients (e.g. morbidly obese patients undergoing rapid weight loss following bariatric surgery) from developing gallstones. However, ursodeoxycholic acid has no effect on the reduction of symptoms once stones have formed.

Clinical features

Differential diagnosis

The differential diagnosis of RUQ pain includes the following:

• Peptic ulcer disease, including perforation

• Acute pancreatitis

• Coronary ischaemia, especially involving the inferior myocardial surface

• Appendicitis, especially retrocaecal or in pregnancy

• Renal disease, including renal colic and pyelonephritis

• Colonic pathology, such as irritable bowel syndrome

• Hepatic pathology, especially hepatitis

• Right lower lobe pneumonia

Clinical investigations

Investigations in biliary pain are aimed at confirming the diagnosis, establishing the presence of gallstones and detecting complications.