Chapter 44. The Extrahepatic Biliary System

The extrahepatic biliary system is composed of the bile ducts and the gallbladder (Figure 44-1). In 70% of patients, the common bile duct and pancreatic duct join at the ampulla of Vater and have a common duodenal opening. In the other 30%, the pancreatic and bile ducts open separately. The common bile duct has a luminal diameter of 0.5–0.7 cm in the adult.

Histologically, the entire biliary tract is lined by mucus-secreting columnar epithelium. In the gallbladder, the epithelium is thrown up into delicate folds, and mucous glands are buried deeply in the smooth muscle wall (Aschoff-Rokitansky sinuses).

The biliary system stores and delivers the bile secreted by the liver into the duodenum, with the gallbladder acting as a reservoir in which the bile is stored and concentrated (from about 1000 mL/d down to 50 mL/d). The gallbladder is not required for adequate functioning of the system. Bile is an alkaline fluid that contains the excretory bilirubin pigments, bile acids and bile salts, cholesterol, inorganic ions, and mucus. Cholesterol, which is insoluble in water, is maintained in solution by the formation of complexes with the hydrophilic bile salts and lecithin.

Pain

Several types of pain occur in diseases of the extrahepatic biliary system. Biliary colic is severe intermittent pain in the right upper abdomen that radiates to the back and right shoulder. It is caused by increased muscular contraction of the bile duct and occurs when there is bile duct obstruction. Vague epigastric pain (dyspepsia), which may be aggravated by ingestion of fatty foods, is common in patients with gallstones and chronic cholecystitis. The mechanism of this pain is unknown. Constant right upper abdominal pain, often severe, occurs in acute cholecystitis when extension of inflammation involves the pain-sensitive parietal peritoneum.

Obstructive Jaundice

(Figure 44-2)

Obstruction of the common bile duct results in obstructive jaundice. The biliary system undergoes dilation proximal to the obstruction, and bile backs up in the liver (cholestasis). The gallbladder undergoes enlargement when it is normal; in patients who have gallstones and fibrotic thickening of the gallbladder wall, gallbladder enlargement does not occur (Courvoisier's law).

Cholecystography & Cholangiography

The biliary tract may be outlined by a radiopaque dye, permitting evaluation of its anatomy. The dye may be given orally or intravenously to be excreted in bile. Oral cholecystography and intravenous cholangiography have a high failure rate in patients with obstructive jaundice because the dye is not excreted in adequate amounts in the bile. Dye may also be injected into the common bile duct through an endoscope in the duodenum (endoscopic retrograde cholangiopancreatography, ERCP) or directly into the dilated intrahepatic ducts in patients with obstructive jaundice (transhepatic cholangiography, THC). ERCP also permits the taking of biopsy specimens from the terminal part of the common bile duct and samples of bile for cytologic study.

Other Radiologic Techniques

Ultrasonography and computerized tomography are extremely accurate in detecting dilated bile ducts, calculi in the biliary system, and masses in the head of the pancreas and bile ducts. When a mass is present, a fine needle may be passed into it under radiologic guidance and material aspirated for cytologic diagnosis (fine-needle aspiration biopsy). Hepatobiliary (HIDA) scans utilize an agent that is rapidly excreted into bile, permitting evaluation of the biliary tract.

Functional Evaluation

Tests to evaluate obstructive jaundice have been considered in Chapter 42: The Liver: I. Structure & Function; Infections. Chemical examination of bile is of little clinical diagnostic value and is rarely performed.

Anatomic Variations of the Biliary System

Minor variations in the way in which the common hepatic, cystic, and common bile ducts connect are very common and frequently associated with varying distributions of the arteries supplying the biliary system and liver. Recognition of these normal variations is important at cholecystectomy in order to prevent accidental ligation of ducts and blood vessels.

Anatomic abnormalities of the gallbladder include absence, duplication with the presence of two gallbladders, intrahepatic location, and floating gallbladder surrounded by peritoneum and connected to the inferior surface of the liver by a pedicle. A peculiar abnormality is a focal concentric narrowing of the body of the gallbladder, producing an expanded fundus (“phrygian cap” gallbladder).

Biliary Atresia

Biliary atresia is the most common cause of neonatal obstructive jaundice. Atresia is failure of development of the lumen in the epithelial cord that ultimately becomes the bile ducts; this failure may be complete or incomplete. The cause of atresia is controversial; some authorities believe it is the result of an intrauterine infection. Atresia commonly involves the extrahepatic bile ducts only; more rarely, the intrahepatic ducts are involved. Complete atresia involving the entire system is associated with a high mortality rate. The liver shows the features of severe large bile duct obstruction with secondary biliary cirrhosis.

Without treatment, death occurs in infancy. Surgical treatment may be successful in cases where atresia is partial. In cases where atresia involves intrahepatic ducts, liver transplantation represents the only hope of survival.

Choledochal Cyst

Choledochal cyst, although uncommon, is the most frequent cause of obstructive jaundice in older children. Choledochal cysts are caused by focal dilation, often massive, of the common bile duct. The wall is thick and fibrotic, and the cavity contains bile. Rarely, dilation of intrahepatic bile ducts (Caroli's disease) may coexist.

Women are more commonly affected. Clinical presentation is with pain, jaundice, and a cystic mass in the right upper quadrant.

Most gallbladder diseases are associated with the formation of gallstones (cholelithiasis). Gallstones are usually formed in the gallbladder and rarely in the common bile duct.

Etiology & Incidence

(Table 44-1)

Cholesterol-Based Gallstones

Pure, mixed, and combined cholesterol-based gallstones are common and are formed when the concentration of cholesterol is increased or when bile salts are decreased. (Bile salts keep cholesterol in solution.) Women are more apt to be affected. Middle age, obesity, and multiparity (“fat, fertile females in their forties and fifties”) increase the risk to as high as 20%. Oral contraceptives increase biliary cholesterol excretion and predispose to gallstones. Three fourths of Native American women develop gallstones. The incidence is also high in South American and Mexican women.

In patients with terminal ileal disease such as Crohn's disease or those who have undergone ileal resection and ileal bypass surgery, failure of bile salt reabsorption in the terminal ileum is associated with decreased bile salt levels in bile and formation of gallstones.

Patients with diabetes mellitus also have an increased incidence of cholesterol gallstones, probably related to increased cholesterol levels in bile.

Pigment (Bilirubin) Stones

These are uncommon and occur (1) in patients suffering from chronic hemolytic anemias such as sickle cell disease and thalassemia, in whom bilirubin excretion is greatly increased; and (2) in patients with parasitic infestations, most commonly Clonorchis sinensis, in whom the parasite ova form a nidus for pigment stones (see Oriental Cholangiohepatitis, Chapter 42: The Liver: I. Structure & Function; Infections).

Clinicopathologic Syndromes

(Figure 44-3)

Asymptomatic Gallstones

Thirty percent or more of patients with gallstones have no symptoms, and gallstones are frequently found incidentally at radiologic examination. Only about 25% of gallstones contain sufficient calcium to be visible on plain x-rays, but ultrasonography and computerized tomography are highly effective at detecting gallstones. The presence of asymptomatic gallstones is not an indication for surgical removal.

Acute Cholecystitis

Acute cholecystitis rarely occurs in the absence of gallstones. In 80% of cases, a stone is found obstructing the cystic duct, leading to stasis of bile in the gallbladder. The residual bile becomes highly concentrated and causes a chemical acute inflammation. The damaged gallbladder is then susceptible to infection by bacteria; Escherichia coli and other gram-negative bacilli are cultured from the bile in 80% of cases.

Pathologically, the gallbladder shows congestion, thickening of the wall by edema, mucosal ulceration, and fibrinous exudation. Large numbers of neutrophils are present. The gallbladder may become filled with pus (empyema of the gallbladder). In severe cases, necrosis of the wall occurs, with greenish-black discoloration (gangrenous cholecystitis). Perforation may lead to local abscess formation or to generalized peritonitis.

Clinically, acute cholecystitis produces acute onset of fever and right upper quadrant pain. An enlarged, tender gallbladder is palpable in 40% of cases; mild jaundice may be seen in about 20%. Treatment is with antibiotics and surgical drainage or cholecystectomy.

Chronic Cholecystitis

Chronic cholecystitis almost never occurs without gallstones. Pathologically, the gallbladder is contracted and its wall thickened by fibrosis (Figure 44-4), with infiltration by lymphocytes, plasma cells, and macrophages. Calcification may occur in the wall; when extensive, the gallbladder is outlined on abdominal x-ray (porcelain gallbladder). The mucosa of the gallbladder may be near normal or thinned by pressure of a stone, or it may show yellow flecks due to accumulation of cholesterol-filled foamy macrophages in the mucosa (cholesterolosis).

Symptoms are usually vague; abdominal pain, often related to the ingestion of fatty foods, is the most common feature. Biliary colic—severe intermittent right upper quadrant pain—may occur when the cystic duct is obstructed.

Movement of Gallstones

Migration of gall-stones from the gallbladder may cause obstruction or fistula formation.

1. Cystic duct obstruction is characterized by distention of the gallbladder with watery bile (hydrops) or mucus (mucocele). Acute cholecystitis also complicates duct obstruction.

2. Common bile duct obstruction may be intermittent, with attacks of biliary colic, jaundice, and high fever due to cholangitis (Charcot's triad of symptoms). Less commonly, obstruction is complete, leading to deep jaundice. In patients with obstructive jaundice resulting from stones, the presence of chronic cholecystitis prevents dilation of the gallbladder (Courvoisier's law; see Figure 44-2). Impaction of a gallstone in the ampulla of Vater may obstruct the pancreatic duct, leading to acute pancreatitis.

3. Fistulous tracts develop rarely between the gallbladder and intestine due to the chronic inflammation. A large gallstone may then pass directly through such a cholecystoenteric fistula into the intestine, causing intestinal obstruction (gallstone ileus).

Fibrous strictures of the common bile duct are an important cause of obstructive jaundice. They occur (1) after biliary surgery, most frequently cholecystectomy; (2) after external trauma (rarely); and (3) following inflammation, either caused by a gallstone in the bile duct or chronic pancreatitis.

Sclerosing cholangitis is a rare specific disease that occurs in patients with chronic ulcerative colitis. Its cause is unknown, but immunologic injury is thought to be involved. The large bile ducts both within and outside the liver undergo irregular fibrosis with narrowing, leading to obstructive jaundice. Sclerosing cholangitis is difficult to distinguish from bile duct carcinoma.

Fibrous strictures of the biliary system, both intrahepatic and extrahepatic, occur in Clonorchis sinensis infection. Multiple strictures of the bile duct are associated with irregular dilation of the biliary system and the presence of numerous pigment stones and sludge containing parasites and ova.

Benign Neoplasms

Benign neoplasms are rare in the biliary system. Papillary adenoma, which may occur at the ampulla of Vater or in the gallbladder, is the most common type. It presents as a polyp.

The biliary tract is a site in which granular cell tumors occur. Granular cell tumors are believed to be variants of schwannomas and are composed of large cells containing an abundance of granular cytoplasm. Although rare, these neoplasms are important because they cause stenosis of the common bile duct and resemble bile duct carcinoma.

Carcinoma of the Gallbladder

Carcinomas of the gallbladder and biliary tree are relatively uncommon—less than 1% of causes of cancer in the United States. Gallbladder carcinoma is much more common in women, following the sex distribution of gallstones (80% of gallbladder carcinomas are associated with gallstones), and occurs with high frequency among Native Americans and persons of Central and South American origin. Chronic cholecystitis with extensive calcification of the wall (porcelain gallbladder) is associated with a 25% incidence of carcinoma.

Grossly, gallbladder carcinoma presents as a polypoid mass that projects into the lumen, with infiltration of the wall (Figure 44-5). In some cases, the infiltrative component dominates, producing thickening of the wall. Histologically, it is an adenocarcinoma of variable differentiation frequently associated with marked fibrosis and a tendency to perineural invasion.

Most cases of gallbladder carcinoma are found in patients being evaluated for gallstones. In advanced disease, there is weight loss, a palpable mass, or evidence of metastases. The prognosis depends on the stage. Tumors confined to the gallbladder have a good prognosis. When there is extension through the wall of the gallbladder into the liver or peritoneum with or without evidence of metastatic disease, the 5-year survival rate is close to zero.

Carcinoma of the Bile Ducts

Although uncommon, bile duct carcinoma represents an important cause of obstructive jaundice in adults. Tumors may involve the hepatic ducts at the hilum of the liver (Klatskin tumor) or the common bile duct, most commonly at its terminal portion (at the ampulla of Vater; Figure 44-6).

Bile duct carcinoma tends to cause obstructive jaundice at an early stage. Histologically, these tumors are usually well differentiated and associated with marked sclerosis.

Bile duct carcinoma grows slowly, with local extension along the biliary system and neighboring structures. Lymph node involvement is early, but bloodstream metastasis usually occurs late. The ultimate prognosis is poor, although many patients have a long survival.