Gallstones are hard, pebble-like objects that develop in and sometimes interfere with normal functioning of the gallbladder. Under normal circumstances, the gallbladder acts as a reservoir for bile that it receives from the liver and periodically discharges into the small intestine. Bile is mostly water, with variable amounts of cholesterol, bile salts, and bilirubin. Gallstones develop when the bile becomes oversaturated with one or more of these. Treatment of symptomatic gallstones is typically laparoscopic removal of the gallbladder, but nonsurgical options can be used in special circumstances. The size and number of gallstones can vary widely.
The stones can be classified based on their composition; most are either predominantly cholesterol or predominantly bilirubin combined with calcium ions. In Europe and the US, gallstones are made predominantly of cholesterol. Pigmented stones of calcium and bilirubin salts are more common in Japan.
Signs and Symptoms
Gallstones may be present without any symptoms and may be found incidentally during surgery or on routine radiologic study. If symptoms are present, they may include:
- Abdominal pain is the most dramatic sign of gallstone disease, and may be severe. The pain is sometimes called biliary colic and is usually felt mostly in the right upper abdomen. This pain may also be felt in the back. The pain is often felt after eating heavy (especially fatty) meals, which cause the gallbladder contraction to be especially active. The pain can be steady or intermittent.
- Jaundice, or yellow discoloration of the skin, indicates that the stone is located in the common bile duct and preventing exit of bile into the small intestine.
- Clay-colored stool (a result of an inability to absorb fat)
- Nausea and vomiting
- Abdominal fullness
Cholesterol gallstones form in bile that is supersaturated with cholesterol from the liver. Stone formation starts with the appearance of microstones that aggregate and grow to form macrostones. It is not known why the liver secretes bile with such a high cholesterol concentration, but some mechanisms have been proposed:
- An enzyme defect that alters the liver's metabolism of cholesterol
- Diminished secretion of bile acids
- Decreased reuptake of bile salts from the small intestine, which decreases the bile acid pool
- Some combination of the above
The cause of pigmented stones (bilirubin and calcium salts) is often related to biliary infection and increased amounts of unconjugated bilirubin in the bile. Hemolysis can contribute to excess unconjugated bilirubin as in, for example, sickle cell anemia. Hemolysis is the breaking open of red blood cells and the release of hemoglobin into the blood stream . Gallstones can cause problems when they become large enough to block the cystic duct that allows fluid to enter and leave the gallbladder.
A tentative diagnosis of gallstones can be made on historical and physical findings, but other causes of acute abdominal pain must be ruled out. Imaging studies can often clinch the diagnosis by identifying stones in the gallbladder or surrounding ducts. Several techniques deserve special mention:
- Abdominal ultrasound is most commonly used to diagnose gallstones and gallbladder inflammation.
- Computed tomography (CT) scan. The CT scan is like an x-ray that produces cross-section images of the body. The test may show the gallstones or complications, such as infection and rupture of the gallbladder or bile ducts.
- Cholescintigraphy (HIDA scan). A small amount of radioactive material is given to the patient. This material is absorbed by the gallbladder, which is then stimulated to contract. The test is used to diagnose abnormal contraction of the gallbladder or obstruction of the bile ducts.
- Endoscopic retrograde cholangiopancreatography (ERCP). ERCP is used to locate and remove stones in the bile ducts. An endoscope is introduced via the throat and stomach into the small intestine. From there, the camera and capture basket are moved into the affected bile duct to allow removal of the offending stone(s).
- Blood tests. Blood tests may be performed to look for signs of infection, obstruction, pancreatitis, or jaundice.
Removal of the gallbladder is the treatment of choice for symptomatic gallstones; this is usually achieved through only a few small incisions that allow a laparoscope and tools to enter the abdomen with minimal surrounding tissue injury in a procedure called a laparoscopic cholecystectomy. The standard open procedure leaves a large incision and significantly longer recovery times.
Chenodeoxycholic acid (Chenix) and ursodeoxycholic acid (Actigall) are bile salts that can be given orally and can dissolve cholesterol-containing stones. These medicines are useful for patients who cannot have surgery for other underlying medical reasons.
Several factors contribute to the overall risk of gallstone disease. These include obesity, female gender, middle age, and parenthood (giving the mnemonic "fat, female, forty, and fertile"). Other risk factors include ancestry, as some ethnic groups are predisposed to gallstone formation. Pima and other American Indian women have prevalence rates of about 75%, for example. People with gallbladder, pancreatic, or intestinal disease are also at increased risk. People with hemolytic anemias are especially prone to pigmented gallstones. One study noted gallstones in 31% of patients with sickle cell anemia.
Other risk factors include diets high in fat and cholesterol and low in fiber, rapid weight loss such as with bariatric (weight loss) surgery, diabetes, and administration of cholesterol-lowering drugs.
Physical exercise also appears to decrease the risk of gallstones in men. Leitzmann MF, Stampfer MJ, Willett WC, Speigelman D, Colditz GA, Giovannucci EL. The relation of physical activity to risk for symptomatic gallstone disease in men. Ann Intern Med. 1998 Mar 15;128(6):417-25. Abstract | Full Text </ref>
Gallstones that become lodged in the biliary tract can cause several related problems:
- Cholecystitis or inflammation of the gallbladder.
- Gallstone pancreatitis can occur when stones block the pancreatic duct, leaving the digestive enzymes that usually exit the pancreas with nowhere to go. This results in partial digestion of the pancreas itself, and is extremely painful.
- Blockage of the hepatic ducts, which carry bile out of the liver
- Blockage of the cystic duct, which takes bile to and from the gallbladder
- Blockage of the common bile duct, which takes bile from the cystic and hepatic ducts to the small intestine.
Bile trapped in these ducts can cause inflammation in the gallbladder, the ducts, or in rare cases, the liver. If any of the bile ducts remain blocked for a significant period of time, severe damage or infection can occur in the gallbladder, liver, or pancreas. Left untreated, the condition can be fatal. Warning signs of a serious problem are fever, jaundice, and persistent pain.
A new surgical procedure, known as NOTES (natural orifice transluminal endoscopic surgery) involves accessing the abdomen through body orifices, eliminating the need for abdominal incisions. The procedure is being studied as a possible option for the removal of the gallbladder (cholecystectomy). 
There is also research ongoing to determine the efficacy of using baloon dilation in conjunction with the traditional endoscopic sphincterotomy (using an endoscope to enlarge the bile duct opening by cutting the sphincter muscle) to make removal of larger gallstones easier. 
The largest American population-based study of gallstone disease (NHANES III) estimated that more than 20 million Americans have undergone gallbladder surgery or currently have gallstones. Gallstone disease in the Western world has an estimated prevalence of 10-15% and more than 75% are cholesterol-enriched gallstones. Ethnic differences in gallbladder disease prevalence differed according to sex. Since the known risk factors only partially explain the epidemiologic patterns observed, there are apparently several unknown risk factors.
The largest gallstone on record was removed from an 80-year old woman in 1952 and weighed 6.29 kg (13.84 pounds). The record number for most gallstones removed from an individual is 3,110.
- ↑ Walker TM, Hambleton IR, Serjeant GR. Gallstones in sickle cell disease: observations from The Jamaican Cohort study. J Pediatr. 2000 Jan;136(1):80-5. Abstract
- ↑ Leitzmann MF, Stampfer MJ, Willett WC, Speigelman D, Colditz GA, Giovannucci EL. Coffee intake is associated with lower risk of symptomatic gallstone disease in women. Gastroenterology. 2002 Dec;123(6):1823-30. Abstract
- ↑ Leitzmann MF, Stampfer MJ, Willett WC, Speigelman D, Colditz GA, Giovannucci EL. A prospective study of coffee consumption and the risk of symptomatic gallstone disease in men. JAMA. 1999 Jun 9;281(22):2106-12. Abstract | Full Text
- ↑ Wagh MS, Thompson CC. Surgery insight: natural orifice transluminal endoscopic surgery--an analysis of work to date. Nat Clin Pract Gastroenterol Hepatol. 2007 Jul;4(7):386-92. Abstract | Full Text
- ↑ Maydeo A, Bhandari S. Balloon sphincteroplasty for removing difficult bile duct stones. Endoscopy. 2007 Nov;39(11):958-61. Epub 2007 Aug 15. Abstract
- ↑ Everhart JE, Khare M, Hill M, Maurer KR. Prevalence and ethnic differences in gallbladder disease in the United States. Gastroenterology. 1999 Sep;117(3):632-9. Abstract
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