Gallstone disease is the most common disorder affecting the body's biliary system, the network of organs and ducts that create, transport, store, and release bile. Bile is a thick fluid, made in the liver and stored in the gallbladder, that acts in the small intestine to digest fat. Bile contains cholesterol, water, proteins, bilirubin (a breakdown product from blood cells), bile salts (the chemicals necessary to digest fat), and small amounts of copper or other materials. If the chemical balance of bile contains too much of any of these components, particularly of cholesterol, crystals form and can harden into stones.
In size, gallstones can be as small as a grain of sand or as large as a golf ball. A person can form one large stone in his or her gallbladder, or hundreds. About 10 percent of the population have gallstones, but the vast majority experience no symptoms and need no treatment. However, in 1 percent to 2 percent of these people, gallstones can cause problems by lodging in bile ducts, stopping the flow of bile or digestive enzymes, and leading to severe abdominal pain, vomiting, inflammation, and even life-threatening infection.
There are two types of gallstones: cholesterol and pigment stones. About 80 percent of all gallstones are cholesterol stones, yellow-green stones made up of hardened cholesterol. Cholesterol stones are associated with bile that contains an overabundance of cholesterol, or is "supersaturated" with cholesterol. The other 20 percent of gallstones are pigment stones, composed of bilirubin and other elements. Pigment stones are often seen in Asian cultures but rarely in U.S. patients. They are black or brown in color, and why they occur is not fully understood. Black pigment stones tend to remain in the gallbladder, whereas brown pigment stones often lodge in bile ducts.
The prevalence of gallstone disease varies worldwide. High rates occur in the United States, Chile, Sweden, Germany, and Austria. Pima Indian women have among the highest rates of gallstone disease in the world; nearly 70 percent have gallstones by age 30. On the other hand, Asian populations have a low incidence of gallstones, and the Masai people of East Africa have none at all.
In the United States, an estimated 10 to 15 percent of adults have gallstone disease. About a million new cases are diagnosed each year, and some 800,000 operations are performed to treat gallstones, making gallstone disease the most common gastrointestinal disorder requiring hospitalization. The medical cost of gallstones in the United States is estimated to be about $5 billion yearly. The primary therapy for gallstones that are causing pain, inflammation, or infection is removal of the gallbladder.
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Gallstones are caused by an imbalance of the substances such as cholesterol that make up bile, a liquid made by the body to digest fat. If there are excessive amounts of cholesterol in bile, for example, crystals form. Over time, the crystals can stick to one another to form stones in the gallbladder, the body's storage tank for bile. If these stones lodge in the neck of the gallbladder or the bile ducts connecting the gallbladder to the liver and the small intestine, pain, inflammation or other symptoms can result, leading to serious complications.
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Cholesterol stones, the most common type of gallstones, account for at least 80 percent of all cases. They form when three conditions exist:
- The bile must be supersaturated with cholesterol, meaning it contains a very large amount compared with the other components of bile.
- The cholesterol in bile must rapidly transform into crystals.
- There may be a decrease in gallbladder contractions. Without proper movement of the gallbladder cholesterol, crystals in the bile remain in the gallbladder long enough to form stones.
Factors that appear to create or encourage these conditions include:
- Use of hormone replacement therapy and birth control pills. These drugs appear to raise the level of cholesterol in bile and also reduce gallbladder movement.
- Use of cholesterol-lowering drugs. Medications such as clofibrate reduce the amount of cholesterol in blood but raise the level in bile.
- Pregnancy. Extra estrogen in a pregnant woman's system results in supersaturation of the bile with cholesterol and decreased gallbladder movement.
- Rapid weight loss. Gallstone formation is one of the most frequent and significant complications of rapid weight loss. Cholesterol is activated from fatty tissue and secreted into the bile, leading to both cholesterol supersaturation and diminished gallbladder contractions. Studies of people on very low calorie weight-loss plans or among people who experience rapid weight loss resulting from gastric bypass surgery indicate that gallstone formation is a common unwanted side effect. Fasting also decreases gallbladder movement and causes bile to overconcentrate cholesterol, leading to gallstones.
No one is sure what causes pigment stones to form. They tend to develop in people who have underlying diseases, including cirrhosis of the liver, biliary tract infections, and hereditary blood disorders such as sickle cell anemia, in which too much bilirubin is formed.
The gallbladder is a small, hollow organ, shaped like a crook-necked squash, that is located under the liver. It is bound by blood vessels, connective tissue, and bile ducts. It is the key storage facility for bile, which is essential to the body's digestive system.
When bile is secreted by the liver, it flows through a system of tubelike ducts, called hepatic ducts, to the gallbladder. There, it is stored until bile is needed to digest fat from food. After a meal, the gallbladder contracts and pushes bile through the cystic duct into another tubelike structure called the common bile duct. The common bile duct then releases bile to the duodenum, the first portion of the small intestine, where it begins to break down fat.
Gallstones can block the flow of bile if they lodge in any part of this complicated system of ducts. If bile becomes trapped in these ducts, it can lead to inflammation of the gallbladder. The end of the common bile duct also allows the flow of digestive enzymes out of the pancreas. If a gallstone blocks the opening to the common bile duct, these enzymes can become trapped in the pancreas and lead to a condition called gallstone pancreatitis, which is extremely painful and serious.
If any portion of this biliary system remains blocked by gallstones for an extended period, possibly fatal infections of the gallbladder, liver, or pancreas can result. Persistent severe pain accompanied by fever, jaundice (yellowing of the skin and whites of the eyes), or clay-colored stools requires immediate medical attention and treatment for gallstone disease.
A number of factors put people at higher risk of gallstones:
Gender: The prevalence of gallstones is higher in women than in men; indeed, studies have shown that gallstone disease is common in young women but rare in young men. Women between the ages of 20 and 60 are three times more likely to develop gallstones than are men in the same age group. And by age 60, 20 percent of American women have gallstones.
One key explanation for the gender difference is that estrogen increases the concentration of cholesterol in bile, leading to an excess of cholesterol and slowed gallbladder movement. During pregnancy, women are especially vulnerable, and multiple pregnancies increase a woman's risk. The estrogen in oral contraceptives and hormone replacement therapy has the same impact on bile and gallbladder movement.
Age: The incidence of gallstone disease increases with age. Generally, young people under age 20 who suffer from gallstones have underlying conditions such as cystic fibrosis. The likelihood of developing gallstones increases after age 60.
Genetics: Family history and ethnicity are critical risk factors in development of gallstones, though no gene responsible for gallstone formation has yet been discovered.
American Indians are at particular risk, because they are known to secrete high levels of cholesterol in bile. A majority of American Indian men have gallstones by age 60, and among Pima Indian women, 70 percent will have gallstones by age 30. Hispanics and Mexican-Americans, particularly women, also have high rates of gallstone disease. And both men and women from Norway and Chile suffer increased rates of gallstone disease.
African-Americans seem to have lower rates of gallstone disease than American Indians, whites, or Hispanics.
Obesity: Obesity is a significant risk factor, particularly for women. Women with a body mass index of over 30—in the obese range—have twice the risk of gallstone disease of women who are not overweight. One explanation for the link between obesity and gallstones is that the overweight condition tends to upset the balance between cholesterol and other components of bile, either by reducing the other components relative to cholesterol or by causing excessive secretion of cholesterol into the bile. Obesity also slows down the emptying of the gallbladder.
Location of body fat: Belly fat, that spare tire around the middle, dramatically increases the chance of developing stones. One recent study of 42,000 healthy nurses showed that when women put on weight around their waists, the risk of developing gallstone disease requiring surgery nearly doubled.
Diabetes: People with diabetes often have high levels of triglycerides in their blood, and these fatty acids tend to increase the risk of gallstones.
Last reviewed on 7/23/09
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