Gallbladder Disease

Pathophysiology, Diagnosis, and Treatment

Simore Afamefuna, PharmD Candidate; Shari N. Allen, PharmD, BCPP


US Pharmacist. 2013;38(3):33-41. 

In This Article


Gallstones are hard, pebble-like structures that obstruct the cystic duct. The formation of gallstones is often preceded by the presence of biliary sludge, a viscous mixture of glycoproteins, calcium deposits, and cholesterol crystals in the gallbladder or biliary ducts.[5] In the U.S., most gallstones consist largely of bile supersaturated with cholesterol.[1,2] This hypersaturation, which results from the cholesterol concentration being greater than its solubility percentage, is caused primarily by hypersecretion of cholesterol due to altered hepatic cholesterol metabolism.[1,3] A distorted balance between pronucleating (crystallization-promoting) and antinucleating (crystallization-inhibiting) proteins in the bile also can accelerate crystallization of cholesterol in the bile.[1–3,5] Mucin, a glycoprotein mixture secreted by biliary epithelial cells, has been documented as a pronucleating protein. It is the decreased degradation of mucin by lysosomal enzymes that is believed to promote the formation of cholesterol crystals.[3]

Loss of gallbladder muscular-wall motility and excessive sphincteric contraction also are involved in gallstone formation.[1] This hypomotility leads to prolonged bile stasis (delayed gallbladder emptying), along with decreased reservoir function.[3,5] The lack of bile flow causes an accumulation of bile and an increased predisposition for stone formation. Ineffective filling and a higher proportion of hepatic bile diverted from the gallbladder to the small bile duct can occur as a result of hypomotility.[1,5]

Occasionally, gallstones are composed of bilirubin, a chemical that is produced as a result of the standard breakdown of RBCs. Infection of the biliary tract and increased enterohepatic cycling of bilirubin are the suggested causes of bilirubin stone formation. Bilirubin stones, often referred to as pigment stones, are seen primarily in patients with infections of the biliary tract or chronic hemolytic diseases (or damaged RBCs).[1,3,6] Pigment stones are more frequent in Asia and Africa.[3,6]

The pathogenesis of cholecystitis most commonly involves the impaction of gallstones in the bladder neck, Hartmann's pouch, or the cystic duct; gallstones are not always present in cholecystitis, however.[5] Pressure on the gallbladder increases, the organ becomes enlarged, the walls thicken, the blood supply decreases, and an exudate may form.[2,5] Cholecystitis can be either acute or chronic, with repeated episodes of acute inflammation potentially leading to chronic cholecystitis. The gallbladder can become infected by various microorganisms, including those that are gas forming. An inflamed gallbladder can undergo necrosis and gangrene and, if left untreated, may progress to symptomatic sepsis.[1,2,5] Failure to properly treat cholecystitis may result in perforation of the gallbladder, a rare but life-threatening phenomenon.[2,5,7] Cholecystitis also can lead to gallstone pancreatitis if stones dislodge down to the sphincter of Oddi and are not cleared, thus blocking the pancreatic duct.[1]