Page 656 - Robbins Basic Pathology by Vinay Kumar, Abul K. Abbas, Jon C. Aster

642 C H A P T E R 15 Liver, Gallbladder, and Biliary Tract
hyperbilirubinemia suggests obstruction of the common
bile duct. The right subcostal region is markedly tender
and rigid as a result of spasm of the abdominal muscles;
occasionally a tender, distended gallbladder can be pal-
pated. Mild attacks usually subside spontaneously over 1
to 10 days; however, recurrence is common. Approximately
25% of symptomatic patients are sufficiently ill to require
surgical intervention.
Symptoms arising from acute acalculous cholecystitis
usually are obscured by the generally severe clinical condi-
tion of the patient. The diagnosis therefore rests on keeping
this possibility in mind.
Chronic cholecystitis does not have the striking manifesta-
tions of the acute forms and is usually characterized by
recurrent attacks of steady epigastric or right upper quad-
rant pain. Nausea, vomiting, and intolerance for fatty foods
are frequent accompaniments.
The diagnosis of acute cholecystitis usually is based on
the detection of gallstones by ultrasonography, typically
accompanied by evidence of a thickened gallbladder wall.
Chronic cholecystitis, on the other hand, is a pathologic
diagnosis based on the examination of the resected gall-
bladder. Attention to this disorder is important because of
the potential for the following serious complications:
• Bacterial superinfection with cholangitis or sepsis
• Gallbladder perforation and local abscess formation
• Gallbladder rupture with diffuse peritonitis
• Biliary enteric (cholecystenteric) fistula, with drainage of periportal fibrogenesis, which eventually leads to scar­
bile into adjacent organs, entry of air and bacteria into
the biliary tree, and potentially gallstone-induced intes-
tinal obstruction (ileus)
• Aggravation of preexisting medical illness, with cardiac,
pulmonary, renal, or liver decompensation
DISORDERS OF EXTRAHEPATIC
BILE DUCTS
Choledocholithiasis and Cholangitis
Choledocholithiasis and cholangitis are considered together
because these conditions frequently go hand in hand. Cho-
ledocholithiasis is the presence of stones within the biliary
tree. In Western nations, almost all stones are derived from
the gallbladder; in Asia, there is a much higher incidence
of primary ductal and intrahepatic, usually pigmented,
stone formation. Choledocholithiasis may not immediately
obstruct major bile ducts; asymptomatic stones are found
in about 10% of patients at the time of surgical cholecystec-
tomy. Symptoms may develop because of (1) biliary
obstruction, (2) cholangitis, (3) hepatic abscess, (4) chronic
liver disease with secondary biliary cirrhosis, or (5) acute
calculous cholecystitis.
Cholangitis is the term used for acute inflammation of the
wall of bile ducts, almost always caused by bacterial infec-
tion of the normally sterile lumen. It can result from any
lesion obstructing bile flow, most commonly choledocholi-
thiasis, and also from surgery involving the biliary tree.
Other causes include tumors, indwelling stents or cathe-
ters, acute pancreatitis, and benign strictures. Bacteria most
likely enter the biliary tract through the sphincter of Oddi,
rather than by the hematogenous route. Ascending cholan-
gitis refers to the propensity of bacteria, once within the
biliary tree, to infect intrahepatic biliary ducts. The usual
pathogens are E. coli, Klebsiella, Enterococci, Clostridium, and
Bacteroides. Two or more organisms are found in half of the
cases. In some world populations, parasitic cholangitis is a
significant problem. Causative organisms include Fasciola
hepatica or schistosomiasis in Latin America and the Near
East, Clonorchis sinensis or Opisthorchis viverrini in the Far
East, and cryptosporidiosis in persons with acquired
immunodeficiency syndrome.
Bacterial cholangitis usually produces fever, chills,
abdominal pain, and jaundice. The most severe form of
cholangitis is suppurative cholangitis, in which purulent
bile fills and distends bile ducts, with an attendant risk
of liver abscess formation. Because sepsis rather than cho-
lestasis is the predominant risk in cholangitic patients,
prompt diagnosis and intervention are imperative.
Secondary Biliary Cirrhosis
Prolonged obstruction of the extrahepatic biliary tree
results in profound damage to the liver itself. The most
common cause of obstruction is extrahepatic cholelithiasis.
Other obstructive conditions include biliary atresia (dis-
cussed later on), malignancies of the biliary tree and head
of the pancreas, and strictures resulting from previous sur-
gical procedures. The initial morphologic features of cho-
lestasis were described earlier and are entirely reversible
with correction of the obstruction. However, secondary
inflammation resulting from biliary obstruction initiates
ring and nodule formation, generating secondary biliary
cirrhosis.
Biliary Atresia
Biliary atresia is a major cause of neonatal cholestasis,
accounting for one third of the cases of cholestasis in infants
and occurring in approximately 1 in 10,000 live births.
Biliary atresia is defined as a complete obstruction of bile flow
caused by destruction or absence of all or part of the extrahepatic
bile ducts. It is the most frequent cause of death from liver
disease in early childhood and accounts for more than half
of the referrals of children for liver transplantation.
The salient features of biliary atresia include
• Inflammation and fibrosing stricture of the hepatic or
common bile ducts
• Inflammation of major intrahepatic bile ducts, with pro-
gressive destruction of the intrahepatic biliary tree
• Florid features of biliary obstruction on liver biopsy (i.e.,
ductular reaction, portal tract edema and fibrosis, and
parenchymal cholestasis)
• Periportal fibrosis and cirrhosis within 3 to 6 months of
birth
Clinical Course
Infants with biliary atresia present with neonatal cholesta-
sis; there is a slight female predominance. Affected infants
have normal birth weights and postnatal weight gain.
Stools become acholic as the disease evolves. Laboratory