PATHOPHYSIOLOGY OF GALLSTONE FORMATION (CHOLELITHIASIS)



Gallstones, the most common cause of biliary tract disease in the United States, occur in 20 to 35 per cent of people by the age of 75 and are of two types: 75 per cent consist primarily of cho­lesterol, whereas 25 per cent, termed pigment stones, are composed of calcium bilirubinate and other calcium salts. Cholesterol, which is insol­uble in water, normally is carried in bile solubi-lized by bile acids and phospholipids. However, in many individuals, not all of whom will develop gallstones, bile contains more cholesterol than can be maintained in stable solution (Fig. 49-1); i.e., it is supersaturated with cholesterol. In the supersaturated bile of many, but not all, such in­dividuals, microscopic cholesterol crystals form.

Gradual deposition of additional layers of cho­lesterol leads to the appearance of macroscopic cholesterol gallstones. The gallbladder is key to gallstone formation; it constitutes an area of bile stasis where slow crystal growth can occur and it also may provide mucus, bacteria, or other ma­terial to act as a nidus to initiate cholesterol crys­tal formation. Many of the recognized predispos­ing factors for cholelithiasis can be understood in terms of the pathophysiological scheme just out­lined: (1) biliary cholesterol saturation is in­creased by estrogens, multiparity, oral contracep­tives, obesity, and terminal ileal disease (which decreases the bile acid pool); (2) bile stasis is in­creased by bile duct strictures, parenteral hyper­alimentation, fasting, and choledochal cysts.
The pathophysiology of pigment stones is less well understood; however increased production of bilirubin (hemolytic states), cirrhosis, and bac­terial deconjugation of bilirubin to a less soluble form are all associated with pigment stone for­mation.