Causes

What causes gallstones?

Gallstones are common; they occur in approximately 20% of women in the US, Canada and Europe, but there is a large variation in prevalence among ethnic groups. For example, gallstones occur 1 ½ to 2 times more commonly among Scandinavians and Mexican-Americans. Among American Indians, gallstone prevalence reaches more than 80%. These differences probably are accounted for by genetic (hereditary) factors. First-degree relatives (parents, siblings, and children) of individuals with gallstones are 1 ½ times more likely to have gallstones than if they did not have a first-degree relative with gallstones. Further support comes from twin studies that genetic factors are important in determining who gets gallstones. Among non-identical pairs of twins (who share 50% of their genes with each other), both individuals in a pair have gallstones 8% of the time. Among identical pairs of twins (who share 100% of their genes with each other), both individuals in a pair have gallstones 23% of the time.

There are several types of gallstones and each type has a different cause.

Cholesterol gallstones

Cholesterol gallstones are made primarily of cholesterol. They are the most common type of gallstone, comprising 80% of gallstones in individuals from Europe and the Americas. Cholesterol is one of the substances that liver cells secrete into bile. (Secretion of cholesterol into bile is an important way in which the liver eliminates excess cholesterol from the body.)

In order for bile to carry cholesterol, the cholesterol must be dissolved in the bile. Cholesterol is a fat, however, and bile is an aqueous or watery solution; fats do not dissolve in watery solutions. In order to make the cholesterol dissolve in bile, the liver also secretes two detergents-bile acids and lecithin-into the bile. These detergents, just like dish-washing detergents, dissolve the fatty cholesterol so that it can be carried by bile through the ducts. If the liver secretes too much cholesterol for the amount of bile acids and lecithin it secretes, some of the cholesterol does not dissolve. Similarly, if the liver does not secrete enough bile acids and lecithin, some of the cholesterol also does not dissolve. In either case, the undissolved cholesterol sticks together and forms particles of cholesterol that grow in size and eventually form larger gallstones.

There are two other processes that promote the formation of cholesterol gallstones though neither process is able to cause cholesterol gallstones by itself. The first is abnormally rapid formation and growth of cholesterol particles into gallstones. Thus, with the same concentrations of cholesterol, bile acids and lecithin in their bile, patients with gallstones form particles of cholesterol more rapidly than individuals without gallstones. The second process that promotes the formation and growth of gallstones is reduced contraction and emptying of the gallbladder that allows bile to sit in the gallbladder longer so that there is more time for cholesterol particles to form and grow.

Pigment gallstones

Pigment gallstones are the second most common type of gallstone. Although pigment gallstones comprise only 15% of gallstones in individuals from Europe and the Americas, they are more common than cholesterol gallstones in Southeast Asia. There are two types of pigment gallstones.

1. black pigment gallstones, and
2. brown pigment gallstones.

Pigment is a waste product formed from hemoglobin, the oxygen-carrying chemical in red blood cells. The hemoglobin from old red blood cells that are being destroyed is changed into a chemical called bilirubin and released into the blood. Bilirubin is removed from the blood by the liver. The liver modifies the bilirubin and secretes the modified bilirubin or into bile.

Black pigment gallstones:

If there is too much bilirubin in bile, the bilirubin combines with other constituents in bile, for example, calcium, to form pigment (so-called because it is dark brown in color). Pigment dissolves poorly in bile and, like cholesterol, it sticks together and forms particles that grow in size and eventually form gallstones. The pigment gallstones that form in this manner are called black pigment gallstones because they are black and hard.

Brown pigment gallstones:

If there is reduced contraction of the gallbladder or obstruction to the flow of bile through the ducts, bacteria may ascend from the duodenum into the bile ducts and gallbladder. The bacteria alter the bilirubin in the ducts and gallbladder, and the altered bilirubin then combines with calcium to form pigment. The pigment then combines with fats in bile (cholesterol and fatty acids from lecithin) to form particles that grow into gallstones. This type of gallstone is called a brown pigment gallstone because it is more brown than black. It also is softer than black pigment gallstones.

Other types of gallstones.

Other types of gallstones are rare. Perhaps the most interesting type of gallstone is the gallstone that forms in patients taking the antibiotic, ceftriaxone (Rocephin). Ceftriaxone is unusual in that it is eliminated from the body in bile in high concentrations. It combines with calcium in bile and becomes insoluble. Like cholesterol and pigment, the insoluble ceftriaxone and calcium form particles that grow into gallstones. Fortunately, most of these gallstones disappear once the antibiotic is discontinued; however, they still may cause problems until they disappear. Another rare type of gallstone is formed from calcium carbonate.

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