Gallstone: Causes of Formation

Gallstones are prevalent throughout the world, more common in the western countries. Like in USA many studies has shown presence of gallstones in at least 20% of women and in 8% of men over the age of 40. Up to 40% in women above 65 years have gallstones. It is estimated that in US alone at least 25 million persons have gallstones and approximately 1 million new cases of gallstone develop each year.

Gallstones are formed because of abnormality in bile constituents. Gallstones are divided into two major types: first one cholesterol stones account for 80% of the total, and the next, pigment stones comprising the remaining. Cholesterol gallstones are of “brown” type and contain more than 50% cholesterol monohydrate plus a mixture of calcium salts, bile pigments, proteins, and fatty acids. Pigment stones are composed mainly of calcium billirubinate and they contain less than 20% cholesterol. Pigment stones are classified into “black” and “brown” types. “Brown” types are formed due to chronic infection of gall bladder.

Cholesterol is insoluble in water. Bile acids, bile salts and bile pigments are required for making the cholesterol, soluble. The most important factor for the causation of gallstone is increased billiary secretion of cholesterol. Increased billiary secretion of cholesterol may occur in association with obesity, high caloric and cholesterol rich diets, or drugs like clofibrate. Genetics play a very important role in the formation of gallstones. In a twin study in Sweden genetic factors accounted for 25%, shared environmental factors for 13%, and individual environmental factors for 62% for the formation of gallstones.

The following are the predisposing factors in the formation of Cholesterol and Pigment Gallstone:

Cholesterol stones:

      Obesity: due to high cholesterol content in blood and higher secretion of biliary cholesterol. In obese people even if cholesterol in normal secretion of biliary cholesterol is higher.

      Demographic/genetic factors: Prevalence of gallstone is highest in North American Indians, Chilean Indians, and Chilean Hispanics, greater in Northern Europe and North America than in Asia. Prevalence is lowest in Japan.

      Female sex: Estrogen a female sex hormone stimulates hepatic lipoprotein receptors, increase uptake of dietary cholesterol, and increase biliary cholesterol secretion. Natural estrogens, other estrogens, and oral contraceptives lead to decreased bile salt secretion and decreased conversion of cholesterol to cholesteryl esters and leads to cholesterol deposition.

      Increasing age: As age increases the biliary secretion of cholesterol also increases, and decreased size of bile acid pool, decreased secretion of bile salts.

      Weight loss: Mobilization of tissue cholesterol leads to increased biliary cholesterol secretion while enterohepatic circulation of bile acids is decreased.

     Drug therapy (clofibrate): Increased biliary secretion of cholesterol.

      Decreased bile acid secretion: As seen in genetic defect and primary billiary cirrhosis.

      Reduced gall bladder motility: This leads to stasis and formation of cholesterol sludge, as seen in fasting, pregnancy, drugs and prolonged parenteral nutrition.

      Decreased phospholipid secretion: Due to genetic defect.

      Miscellaneous: High calorie, high fat diet and spinal cord injury.

Pigment Stones

Demographic/genetic factors: Asia, rural setting.

Alcoholic cirrhosis

Chronic biliary tract infection, parasite infections.

Chronic hemolysis.

Pernicious anemia.

Increasing age.

Ileal disease, ileal resection or bypass.

Cystic fibrosis

Black pigment stones are composed of either pure calcium bilirubinate or polymer like complexes with calcium and mucin glycoproteins. They are more common in patients of chronic hemolytic states (with increased conjugated billirubin in bile), liver cirrhosis, Gilbert’s syndrome and cystic fibrosis. Brown pigment stones are composed mainly of calcium salts of unconjugated bilirubin with varying amounts of cholesterol and protein. Pigment stone formation is especially prominent in Asians and is often associated with infections in the gall bladder and biliary tree.