Disorders of the biliary tract affect a significant portion of the worldwide population, and the overwhelming majority of cases are attributable to cholelithiasis (gallstones). In the United States, 20% of persons older than 65 years have gallstones and 1 million newly diagnosed cases of gallstones are reported each year.
To better understand these disorders, a brief discussion of the normal structure and function of the biliary tree is needed. Bile is the exocrine secretion of the liver and is produced continuously by hepatocytes. It contains cholesterol and waste products, such as bilirubin and bile salts, which aid in the digestion of fats. Half the bile produced runs directly from the liver into the duodenum via a system of ducts, ultimately draining into the common bile duct (CBD). The remaining 50% is stored in the gallbladder. In response to a meal, this bile is released from the gallbladder via the cystic duct, which joins the hepatic ducts from the liver to form the CBD. The CBD runs in the hepatodudoenal ligament and then courses through the head of the pancreas for approximately 2 cm; it joins the terminal part of the pancreatic duct to form the apulla of Vater before passing through the papilla of Vater into the duodenum. 
Biliary obstruction refers to the blockage of any duct that carries bile from the liver to the gallbladder or from the gallbladder to the small intestine. This can occur at various levels within the biliary system. The major signs and symptoms of biliary obstruction result directly from the failure of bile to reach its proper destination.
The clinical setting of cholestasis or failure of biliary flow may be due to biliary obstruction by mechanical means or by metabolic factors in the hepatic cells. For the sake of simplicity, the primary focus of this article is mechanical causes of biliary obstruction, further separating them into intrahepatic and extrahepatic causes. The discussion of intracellular/metabolic causes of cholestasis is very complex, the pathogenesis of which is not always clearly defined. Therefore, these causes are mentioned but are not discussed in detail.
Intrahepatic cholestasis generally occurs at the level of the hepatocyte or biliary canalicular membrane. Causes include hepatocellular disease (eg, viral hepatitis, drug-induced hepatitis), drug-induced cholestasis, biliary cirrhosis, and alcoholic liver disease. In hepatocellular disease, interference in the 3 major steps of bilirubin metabolism, ie, uptake, conjugation, and excretion, usually occurs. Excretion is the rate-limiting step and is usually impaired to the greatest extent. As a result, conjugated bilirubin predominates in the serum.
Extrahepatic obstruction to the flow of bile may occur within the ducts or secondary to external compression. Overall, gallstones are the most common cause of biliary obstruction. Other causes of blockage within the ducts include malignancy, infection, and biliary cirrhosis. External compression of the ducts may occur secondary to inflammation (eg, pancreatitis) and malignancy. Regardless of the cause, the physical obstruction causes a predominantly conjugated hyperbilirubinemia.
Accumulation of bilirubin in the bloodstream and subsequent deposition in the skin causes jaundice (icterus). Conjunctival icterus is generally a more sensitive sign of hyperbilirubinemia than generalized jaundice. Total serum bilirubin values are normally 0.2-1.2 mg/dL. Jaundice may not be clinically recognizable until levels are at least 3 mg/dL.  Urine bilirubin is normally absent. When it is present, only conjugated bilirubin is passed into the urine. This may be evidenced by dark-colored urine seen in patients with obstructive jaundice or jaundice due to hepatocellular injury. However, reagent strips are very sensitive to bilirubin, detecting as little as 0.05 mg/dL. Thus, urine bilirubin may be found before serum bilirubin reaches levels high enough to cause clinical jaundice.
The lack of bilirubin in the intestinal tract is responsible for the pale stools typically associated with biliary obstruction. The cause of itching (pruritus) associated with biliary obstruction is not clear. Some believe it may be related to the accumulation of bile acids in the skin. Others suggest it may be related to the release of endogenous opioids.
Causes of biliary obstruction can be separated into intrahepatic and extrahepatic.
Mechanical or intrahepatic causes are most commonly hepatitis and cirrhosis. Drugs may also cause direct damage to hepatocytes and metabolic obstruction. Note the following:
Hepatitis is inflammation of the liver characterized by diffuse or patchy necrosis. Causes of hepatitis include viruses, drugs, and alcohol.
Cirrhosis is characterized by generalized disorganization of hepatic architecture with nodule formation and scarring in the parenchyma. Cirrhosis results from chronic, not acute, inflammation of the liver. Although many causes exist, the majority of cases of cirrhosis in the United States are sequelae of alcoholic hepatitis or chronic hepatitis B and C infections. PBC is a chronic, progressive, nonsuppurative, granulomatous destruction of the intrahepatic ducts. PBC, an autoimmune destruction of small hepatic ducts, is more common in women than in men.
Drugs, such as anabolic steroids and chlorpromazine, are known to directly cause cholestasis (by mechanisms not entirely understood). Thiazide diuretic use may slightly increase the risk for developing gallstones, the most common cause of biliary obstruction. Amoxicillin/clavulanic acid (Augmentin) is one of the most frequent causes of acute cholestatic injury that can mimic biliary obstruction. Other drugs, such as acetaminophen or isoniazid, can cause hepatocellular necrosis. Typically, drug-induced jaundice appears early with associated pruritus, but the patient's well-being shows little alteration. Generally, symptoms subside promptly when the offending drug is removed.
Extrahepatic causes may be further subdivided into those that are intraductal and those that are extraductal.
Intraductal causes include neoplasms, stone disease, biliary stricture, parasites, primary sclerosing cholangitis (PSC), AIDS-related cholangiopathy, and biliary tuberculosis.
Extraductal obstruction caused by external compression of the biliary ducts may be secondary to neoplasms, pancreatitis, or cystic duct stones with subsequent gallbladder distension.
Neoplasms are various tumors that may lead to biliary obstruction.
Cholangiocarcinomas (rare tumors arising from the biliary epithelium), ampullary carcinomas (neoplasms of the ampulla of Vater), and gallbladder carcinomas (tumors with extension into the CBD) cause obstruction within the ducts.
Metastatic tumors (usually from the gastrointestinal tract or the breast) and the secondary adenopathies in the porta hepatis that may be associated with these tumors can cause external bile duct compression.
Of pancreatic tumors, 60% occur in the head of the pancreas and manifest early with obstructive jaundice.
Stone disease is the most common cause of obstructive jaundice. Gallstones may pass through the CBD and cause obstruction and symptoms of biliary colic and cholecystitis. Larger stones can become lodged in the CBD and cause complete obstruction, with increased intraductal pressure throughout the biliary tree. Mirizzi syndrome is the presence of a stone impacted in the cystic duct or the gallbladder neck, causing inflammation and external compression of the common hepatic duct and thus biliary obstruction.
Of biliary strictures, 95% are due to surgical trauma and 5% are due to external injury to the abdomen or pancreatitis or erosion of the duct by a gallstone. Stone disease is the most common cause of biliary strictures in patients who have not undergone an operation. A tear in the duct causes bile leakage and predisposes the patient to a localized infection. In turn, this accentuates scar formation and the ultimate development of a fibrous stricture.
Of parasitic causes, adult Ascaris lumbricoides can migrate from the intestine into the bile ducts, thereby obstructing the extrahepatic ducts. Eggs of certain liver flukes (eg, Clonorchis sinensis, Fasciola hepatica) can obstruct the smaller bile ducts within the liver, resulting in intraductal cholestasis. This is more common in Asian countries. 
PSC is most common in men aged 20-40 years, and the cause is unknown. However, PSC is commonly associated with inflammatory bowel disease (IBD), most commonly in patients with pancolitis. IBD (the vast majority being ulcerative colitis) is present in 60-80% of patients with PSC, and PSC is found in approximately 3% of patients with ulcerative colitis. PSC is characterized by diffuse inflammation of the biliary tract, causing fibrosis and stricture of the biliary system. It generally manifests as a progressive obstructive jaundice and is most readily diagnosed based on findings from endoscopic retrograde cholangiopancreatography (ERCP).
AIDS-related cholangiopathy manifests as abdominal pain and elevated liver function test results, suggesting obstruction. The etiology of this disorder in patients who are HIV-positive is thought to be infectious (cytomegalovirus, Cryptosporidium species, and microsporidia have been implicated). Direct cholangiography often reveals abnormal findings in the intrahepatic and extrahepatic ducts that may closely resemble PSC.
Biliary tuberculosis is extremely rare. However, with the resurgence of tuberculosis and the emergence of Mycobacterium tuberculosis strains that are resistant to many drugs, biliary tuberculosis may be encountered more frequently in the future. Histopathologic evidence of caseating granulomatous inflammation with bile cytology revealing M tuberculosis is confirmatory. Polymerase chain reaction is useful to expedite the diagnosis if biliary tuberculosis is being considered.
Biliary obstruction associated with pancreatitis is observed most commonly in patients with dilated pancreatic ducts due to either inflammation with fibrosis of the pancreas or a pseudocyst.
Notably, intravenous feedings predispose patients to bile stasis and a clinical picture of obstructive jaundice. Consider this in the evaluation of biliary obstruction.
Sump syndrome is an uncommon complication of a side-to-side choledochoduodenostomy in which food, stones, or other debris accumulate in the CBD and thereby obstruct normal biliary drainage.
United States data
The incidence of biliary obstruction is approximately 5 cases per 1000 people.
The racial predilection depends on the cause of the biliary obstruction. Gallstones are the most common cause of biliary obstruction. Persons of Hispanic origin and Northern Europeans have a higher risk of gallstones compared to people from Asia and Africa.
Native Americans (particularly Pima Indians) have an increased incidence of obesity and diabetes within their population and are especially prone to developing gallstones. Pima women have a lifetime chance of developing gallstones as high as 80%.
The sexual predilection also depends on the specific cause of the biliary obstruction. Gallstone disease is the most common cause of biliary obstruction. Women are much more likely to develop gallstones than men. By the sixth decade, almost 25% of American women develop gallstones, with as many as 50% of women aged 75 years developing gallstones. This increased risk is likely caused by the effect of estrogen on the liver, causing it to remove more cholesterol from the blood and diverting it into the bile.
Approximately 20% of men aged 75 years have gallstones, with more complicated disease courses occurring in those who have had cholecystectomies.
The prognosis as well as the mortality and morbidity of biliary obstruction depends on the cause.
Note the following:
The complications of cholestasis are proportional to the duration and intensity of the jaundice.
High-grade biliary obstruction begins to cause cell damage after approximately 1 month and, if unrelieved, may lead to secondary biliary cirrhosis.
Acute cholangitis is another complication associated with obstruction of the biliary tract and is the most common complication of a stricture, most often at the level of the CBD. Bile normally is sterile. In the presence of obstruction to flow, stasis favors colonization and multiplication of bacteria within the bile. Concomitant increased intraductal pressure can lead to the reflux of biliary contents and bacteremia, which can cause septic shock and death. For this reason, medical treatment of the patient with cholangitis serves only as a temporizing measure. Long-term relief of the biliary obstruction, whether it be surgical, percutaneous, or endoscopic, is necessary to prevent an adverse outcome. 
Patients with biliary obstruction who undergo biliary tract surgery may develop postoperative acute oliguric renal failure. The complication may be due to nephrotoxic bile salts and pigments, endotoxins, or inflammatory mediators. Elderly patients who are deeply jaundiced are more likely to develop postoperative oliguric renal failure than patients of the same age without jaundice.
Biliary colic that recurs at any point after a cholecystectomy should prompt evaluation for possible choledocholithiasis.
Failure of bile salts to reach the intestine results in fat malabsorption with steatorrhea. In addition, the fat-soluble vitamins A, D, E, and K are not absorbed, resulting in vitamin deficiencies. Disordered hemostasis with an abnormally prolonged PT may further complicate the course of these patients. Cholestyramine and colestipol, used to treat pruritus, bind to bile salts and can exacerbate these vitamin deficiencies.
Persistent cholestasis from any cause may be associated with deposits of cholesterol in the skin (cutaneous xanthomatosis) and, occasionally, in bones and peripheral nerves.
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