Gallstones afflict 10% to 20% of adults residing in Western countries in the Northern Hemisphere, 20% to 40% in Latin American countries, and only 3% to 4% in Asian countries. In the United States, about 1 million new cases of gallstones are diagnosed annually, and two-thirds of individuals so affected undergo surgery, resulting in the removal of as much as 25 to 50 million tons of stones per year! There are two main types of gallstones: cholesterol stones, containing crystalline cholesterol monohydrate (80% of stones in Western countries), and pigment stones, made of bilirubin calcium salts.
Bile formation is the only significant pathway for elimination of excess cholesterol from the body, either as free cholesterol or as bile salts. Cholesterol is rendered water-soluble by aggregation with bile salts and lecithins. When cholesterol concentrations exceed the solubilizing capacity of bile (supersaturation), cholesterol can no longer remain dispersed and crystallizes out of solution. Cholesterol gallstone formation is enhanced by hypomobility of the gallbladder (stasis), which promotes nucleation, and by mucus hypersecretion, with consequent trapping of the crystals, thereby enhancing their aggregation into stones.
Pigment stones form when the bile contains a high concentration of unconjugated bilirubin in the biliary tree, as may occur in patients with chronic extravascular red cell hemolysis or with certain infections of the biliary tract, such as liver flukes. The precipitates are primarily insoluble calcium bilirubinate salts.
The major risk factors for gallstones are listed in
Table 16.6 . In up to 80% of individuals with gallstones, the only identifiable risk factors are age and gender. Some elaboration on these risk factors follows: • Age and gender. The prevalence of gallstones increases throughout life. In the United States, less than 5% to 6% of the population younger than 40 years of age has stones, in contrast with 25% to 30% of those older than http://ebooksmedicine.net
Table 16.6 Risk Factors for Gallstones
Demography:NorthernEuropeans,NorthandSouthAmericans,Native
Americans,MexicanAmericansAdvancingageFemalesexhormones
Demography:AsianmorethanWestern,ruralmorethanurbanChronichemolysis(e.g.,sicklecellanemia,hereditaryspherocytosis)BiliaryinfectionGastrointestinaldisorders:ilealdisease(e.g.,Crohndisease),ileal resectionorbypass,cysticfibrosiswithpancreaticinsufficiency 80 years of age. The prevalence in women of all ages is about twice as high as in men.
Ethnic and geographic. Cholesterol gallstone prevalence approaches 50% to 75% in certain Native American populations (Pima, Hopi, and Navajo), whereas pigment stones are rare. The high prevalence in these populations seems to be related to biliary cholesterol hypersecretion.
Heredity. In addition to ethnicity, a positive family history imparts increased risk, as do a variety of inborn errors of metabolism, such as those associated with impaired bile salt synthesis and secretion.
Environment. Estrogens increase hepatic cholesterol uptake and synthesis, leading to excess biliary secretion of cholesterol. These effects explain the increased risk for gallstone disease with oral contraceptive use and with pregnancy. Obesity, rapid weight loss, and treatment with the hypocholesterolemic agent clofibrate also are strongly associated with increased biliary cholesterol secretion and risk for gallstone disease.
Acquired disorders. Any condition in which gallbladder motility is reduced predisposes to gallstones, such as pregnancy, rapid weight loss, and spinal cord injury. In most cases, however, gallbladder hypomotility is present without obvious cause.