1. How are gallstones formed?

Gallstone formation occurs because certain substances in the bile are present
in concentrations that approach the limits of their solubility. When bile is
concentrated in the gallbladder, it can become supersaturated with these substances,
which then precipitate from the solution as microscopic crystals. The crystals are
trapped in the gallbladder mucus, producing gallbladder sludge. Over time, the
crystals grow, aggregate, and fuse to form macroscopic stones. Occlusion of the
ducts by sludge and/or stones produces the complications of gallstone disease.
The two main substances involved in gallstone formation are cholesterol
and calcium bilirubinate.
2. What medications increase the risk for the formation of gallstones?
A number of medications are associated with the formation of cholesterol
gallstones. Estrogens administered for contraception or for the treatment of prostate
cancer increase the risk of cholesterol gallstones by increasing biliary cholesterol
secretion. Clofibrate and other fibrate hypolipidemic drugs increase hepatic
elimination of cholesterol via biliary secretion and appear to increase the risk of
cholesterol gallstones. Somatostatin analogues appear to predispose to gallstones
by decreasing gallbladder emptying.
3. When is surgical intervention indicated in the treatment of gallstones
(cholelithiasis)?
The treatment of gallstones depends upon the stage of disease. [20] Ideally,
interventions in the lithogenic state could prevent gallstone formation, although,
currently, this option is limited to a few special circumstances. Asymptomatic
gallstones may be managed expectantly.
Once gallstones become symptomatic, definitive surgical intervention with
cholecystectomy is usually indicated (typically, laparoscopic cholecystectomy is
the first-line therapy at centers with experience in this procedure). [21] Careful
selection of patients is warranted and should fulfill the following criteria:
- Small stone size (<0.5 to 1 cm)
- Good gallbladder function (eg, normal filling and emptying)
- Minimal or no calcification
Open surgery may be indicated when concomitant gallbladder cancer is
present. In patients with complicated cholecystitis, stabilization of the patient and
gallbladder drainage, followed by cholecystectomy, may be considered
4. Which medications are used for the management of gallstones (cholelithiasis)?
Medical treatments for gallstones, used alone or in combination, include the
following:
- Oral bile salt therapy (ursodeoxycholic acid) (particularly for x-ray-negative
cholesterol gallstones in patients with normal gallbladder function)
- Extracorporeal shockwave lithotripsy (particularly for noncalcified cholesterol
gallstones in patients with normal gallbladder function)
5. What should be included in the differential diagnoses of gallstones
(cholelithiasis)?
Consider that both intra-abdominal and extra-abdominal pathology can
present as upper abdominal pain, and that these conditions may coexist with
cholelithiasis. Among the different entities to consider are peptic ulcer
disease, pancreatitis (acute or chronic), hepatitis, dyspepsia, gastroesophageal
reflux disease (GERD), irritable bowel syndrome, esophageal spasm, pneumonia,
cardiac chest pain, and diabetic ketoacidosis. A careful history and physical
examination should guide further workup.
6. What are the stages of gallstone disease (cholelithiasis)?
Gallstone disease may be thought of as having the following four stages:
- Lithogenic state, in which conditions favor gallstone formation
- Asymptomatic gallstones
- Symptomatic gallstones, characterized by episodes of biliary colic
- Complicated cholelithiasis
7. What is biliary colic?
Pain termed biliary colic occurs when gallstones or sludge fortuitously impact in
the cystic duct during a gallbladder contraction, increasing the gallbladder wall
tension. In most cases, the pain resolves over 30 to 90 minutes as the gallbladder
relaxes and the obstruction is relieved.
8. Why is ultrasonography the imaging study of choice in the workup of
suspected gallstone disease (cholelithiasis)?
Ultrasonography is the procedure of choice in suspected gallbladder or biliary
disease; it is the most sensitive, specific, noninvasive, and inexpensive test for the
detection of gallstones. [14] Moreover, it is simple, rapid, and safe in pregnancy,
and it does not expose the patient to harmful radiation or intravenous contrast. An
added advantage is that it can be performed by skilled practitioners at the bedside.
 The American College of Radiology (ACR) in its Appropriateness Criteria right
upper quadrant pain, published in 2010, supports this conclusion. [15]
Sensitivity is variable and dependent upon operator proficiency, but in general, it is
highly sensitive and specific for gallstones greater than 2 mm. It is less so for
microlithiasis or biliary sludge.
9. What are initial and chronic complications of gallstones (cholelithiasis)?
A gallstone in the common bile duct may impact distally in the ampulla of Vater,
the point where the common bile duct and pancreatic duct join before opening into
the duodenum. Obstruction of bile flow by a stone at this critical point may lead to
abdominal pain and jaundice. Stagnant bile above an obstructing bile duct stone
often becomes infected, and bacteria can spread rapidly back up the ductal system
into the liver to produce a life-threatening infection called ascending cholangitis.
Obstruction of the pancreatic duct by a gallstone in the ampulla of Vater can trigger
activation of pancreatic digestive enzymes within the pancreas itself, leading to
acute pancreatitis.
Chronically, gallstones in the gallbladder may cause progressive fibrosis and loss
of function of the gallbladder, a condition known as chronic cholecystitis. Chronic
cholecystitis predisposes to gallbladder cancer.