The gallbladder is small sac-like organ, which sits just under the liver in the right upper abdomen. It stores and concentrates bile produced by the liver; the bile is released into the small intestine as needed to aid in fat digestion. Bile is a chemically complex fluid; two of the components--cholesterol and bilirubin--are important in the formation of gallstones. A gallstone forms when substances in the bile form solid crystals that aggregate to form stones. Gallstone size ranges from smaller than a grain of sand to larger than a chestnut. A person with gallstone disease may have a single stone or many stones of various sizes. Gallstones are divided into two main types, cholesterol stones and pigment stones.
Cholesterol
The liver breaks down cholesterol to form bile acids. The liver's production of bile salts and the secretion of cholesterol itself into the bile are the body's primary mechanism to get rid of excess total body cholesterol. People who form cholesterol gallstones have an excessive amount of cholesterol in their bile. The overabundance of cholesterol causes it to form a fatty, crystalline solid. Predisposing factors for the formation of cholesterol gallstones include obesity, diabetes, a high-calorie and high-fat diet, high estrogen levels and rapid weight loss. Each of these risk factors causes increased secretion of cholesterol into the bile, which can lead to cholesterol gallstone formation.
Bilirubin
Bilirubin is the breakdown product of hemoglobin, the substance in red blood cells that carries oxygen to the body's cells. Each day, old red blood cells are removed from the circulation and replaced by new ones. As the old red blood cells are broken down, bilirubin is released. The liver processes the bilirubin, which is secreted into the bile. Diseases and conditions that increase the body's bilirubin load or decrease the liver's capacity to process bilirubin can cause an abnormally high concentration of free bilirubin in the bile. The overabundance of bilirubin causes it to form crystals with the mineral calcium.
Calcium bilirubinate crystals are the primary component of pigment gallstones. They are called pigment stones because of their black coloration. Pigment stones that form in the presence of infection or inflammation contain fatty acids in addition to calcium bilirubinate. These pigment stones are typically brown rather than black.
Mucin and Nucleating Proteins
When either cholesterol or calcium bilirubinate crystals initially form in the bile, they are present as individual microscopic solids--a far cry from a stone at this stage. However, a sugar-containing protein called mucin and other proteins interact with the individual crystals, helping them bind together to form a stone. This process is called nucleation. Mucin and other nucleating proteins are present in all gallstones.
References
- "Harrison's Principles of Internal Medicine, 16th Edition"; Anthony S. Fauci, M.D., Eugene Braunwald, M.D., J. Larry Jameson, M.D., Ph.D., Dennis L. Kasper, M.D., Stephen L. Hauser, M.D., Dan L. Longo, M.D., Editors; 2004
- American Gastroenterological Association: Gallstones, how they form
- Merck Manual: Cholelithiasis
- Mayo Clinic: Gallstones
- National Institute of Diabetes and Digestive and Kidney Diseases: Gallstones
