Background

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. [1]

Pathophysiology
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. [2] 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.

Etiology
Causes of biliary obstruction can be separated into intrahepatic and
extrahepatic.
Intrahepatic causes
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
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. [3]
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.

Epidemiology
United States data
The incidence of biliary obstruction is approximately 5 cases per 1000 people.
Race-related demographics
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%.
Sex-related demographics
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.

Prognosis
The prognosis as well as the mortality and morbidity of biliary obstruction
depends on the cause.
Complications
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. [4]
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