Page 655 - Robbins Basic Pathology by Vinay Kumar, Abul K. Abbas, Jon C. Aster

Clinical Features
70% to 80% of individuals with gallstones remain asymp-
tomatic throughout life, with the risk of symptoms dimin-
ishing over time. In the unfortunate minority, however, the
symptoms are striking. There is usually pain, often excru-
ciating, which typically localizes to the right upper quad-
rant or epigastric region and can be constant or, less
commonly, spasmodic. Such “biliary” pain is caused by
gallbladder or biliary tree obstruction, or by inflammation
of the gallbladder itself. More severe complications include
empyema, perforation, fistulas, inflammation of the biliary
tree, and obstructive cholestasis or pancreatitis. The larger
the calculi, the less likely they are to enter the cystic or
common ducts to produce obstruction; it is the very small
stones, or “gravel,” that are more dangerous. Occasionally
a large stone may erode directly into an adjacent loop of
small bowel, generating intestinal obstruction (gallstone
ileus).
Cholecystitis
Inflammation of the gallbladder may be acute, chronic, or
acute superimposed on chronic, and almost always occurs
in association with gallstones. In the United States, chole-
cystitis is one of the most common indications for abdomi-
nal surgery. Its epidemiologic distribution closely parallels
that of gallstones.
MORPHOLOGY
In acute cholecystitis, the gallbladder usually is enlarged
and tense, and it assumes a bright red or blotchy, violaceous
color, the latter imparted by subserosal hemorrhages. The
serosa frequently is covered by a fibrinous, or in severe
cases, fibrinopurulent exudate. In 90% of cases, stones are
present, often obstructing the neck of the gallbladder or the
cystic duct. The gallbladder lumen is filled with cloudy or
turbid bile that may contain fibrin, blood, and frank pus.
When the contained exudate is mostly pus, the condition is
referred to as empyema of the gallbladder. In mild cases
the gallbladder wall is thickened, edematous, and hyperemic.
In more severe cases the gallbladder is transformed into a
green-black necrotic organ—a condition termed gangre-
nous cholecystitis. On histologic examination, the inflam-
matory reactions are not distinctive and consist of the usual
patterns of acute inflammation (i.e., edema, leukocytic infil-
tration, vascular congestion, frank abscess formation, or gan-
grenous necrosis).
The morphologic changes in chronic cholecystitis are
extremely variable and sometimes subtle. The mere presence
of stones within the gallbladder, even in the absence of acute
inflammation, often is taken as sufficient justification for the one third of cases. Unlike acute calculous cholecystitis,
diagnosis. The gallbladder may be contracted, of normal size,
or enlarged. Mucosal ulcerations are infrequent; the submu-
cosa and subserosa often are thickened from fibrosis. In the
absence of superimposed acute cholecystitis, mural lympho-
cytes are the only signs of inflammation.
Acute Calculous Cholecystitis
Acute inflammation of a gallbladder that contains stones is
termed acute calculous cholecystitis and is precipitated by
obstruction of the gallbladder neck or cystic duct. It is the
Gallbladder Diseases 641
most common major complication of gallstones and the most
common reason for emergency cholecystectomy. Manifestations
of obstruction may appear with remarkable suddenness
and constitute a surgical emergency. In some cases,
however, symptoms may be mild and resolve without
medical intervention.
Acute calculous cholecystitis is initially the result of
chemical irritation and inflammation of the gallbladder
wall in the setting of obstruction to bile outflow. The action
of phospholipases derived from the mucosa hydrolyzes
biliary lecithin to lysolecithin, which is toxic to the mucosa.
The normally protective glycoprotein mucous layer is dis-
rupted, exposing the mucosal epithelium to the direct
detergent action of bile salts. Prostaglandins released
within the wall of the distended gallbladder contribute
to mucosal and mural inflammation. Distention and
increased intraluminal pressure also may compromise
blood flow to the mucosa. These events occur in the absence
of bacterial infection; only later may bacterial contamina-
tion develop.
Acute Acalculous Cholecystitis
Between 5% and 12% of gallbladders removed for acute
cholecystitis contain no gallstones. Most cases occur in seri-
ously ill patients. Some of the most common predisposing
insults are
• Major, nonbiliary surgery
• Severe trauma (e.g., from motor vehicle crashes)
• Severe burns
• Sepsis
Other contributing factors include dehydration, gallblad-
der stasis and sludging, vascular compromise, and, ulti-
mately, bacterial contamination.
Chronic Cholecystitis
Chronic cholecystitis may be the sequel to repeated bouts
of acute cholecystitis, but in most instances it develops
without any history of acute attacks. Like acute cholecysti-
tis it is almost always associated with gallstones. However,
gallstones do not seem to have a direct role in the initiation
of inflammation or the development of pain, because
chronic acalculous cholecystitis causes symptoms and mor-
phologic alterations similar to those seen in the calculous
form. Rather, supersaturation of bile predisposes the
patient to both chronic inflammation and, in most instances,
stone formation. Microorganisms, usually E. coli and
enterococci, can be cultured from the bile in only about
stone obstruction of gallbladder outflow in chronic chole-
cystitis is not a requisite. Most gallbladders removed at
elective surgery for gallstones show features of chronic
cholecystitis, making it likely that biliary symptoms emerge
after long-term coexistence of gallstones and low-grade
inflammation.
Clinical Features
Acute calculous cholecystitis presents with biliary pain that
lasts for more than 6 hours. The pain is severe, usually
steady, upper abdominal in location, and often radiates
to the right shoulder. Fever, nausea, leukocytosis, and
prostration are classic; the presence of conjugated