Cholelithiasis and Gallstones

• Cholelithiasis refers to the presence of gallstones in the gallbladder.
• Gallstones affect 10-20% of adults in the US, Canada, and Europe.
• The prevalence is 20-40% in Latin American countries.
• The prevalence is 3-4% in Asian countries.
• Approximately 1 million new cases of gallstones are diagnosed annually in the United States.
• Two-thirds of affected individuals undergo surgery to remove 25 to 50 tons of stones per year.
• Cholesterol stones and pigment stones are the two main types of gallstones.

Cholesterol Stones

• Cholesterol stones contain crystalline cholesterol monohydrate.
• 80% of stones in the United States, Canada, and Europe are cholesterol stones.
• Cholesterol gallstones are more prevalent in the United States and Western Europe (90%).
• The prevalence rate can approach 50% in Native American groups like the Pima, Hopi, and Navajo.
• They arise exclusively in the gallbladder.
• Pure cholesterol stones are pale yellow and consist of 50-100% cholesterol.
• Increasing proportions of calcium carbonate, phosphates, and bilirubin impart gray-white to black discoloration.
• Most are radiolucent, but up to 20% may be radiopaque due to calcium carbonate content.

Pigment Stones

• Pigment stones are made of bilirubin calcium salts.
• Pigment gallstones are the predominant type in non-Western populations.
• They arise primarily in individuals with diseases leading to chronic red cell hemolysis.
• They may arise anywhere in the biliary tree.
• Black pigment stones are found in sterile gallbladder bile.
• Brown stones are found in infected intra-hepatic or extrahepatic ducts.
• They contain calcium salts of unconjugated bilirubin, other calcium salts, mucin glycoproteins, and cholesterol.
• 50% to 75% of black stones are radiopaque due to calcium carbonates and phosphates.
• Brown stones are radiolucent since they contain calcium soaps.

Risk Factors for Gallstones

• Age and sex are identifiable risk factors in up to 80% of individuals with gallstones.
• Gallstone prevalence increases with age.
• Less than 5% to 6% of the population younger than 40 years have stones.
• 25% to 30% of those older than 80 years have stones.
• The prevalence in women of all ages is about twice as high as in men.
• A positive family history imparts increased risk.
• Inborn errors of metabolism (impaired bile salt synthesis and secretion) increase risk.
• Approximately 25% of the risk of cholelithiasis is determined by genetics.
• Estrogens increase hepatic cholesterol uptake and synthesis, leading to excess biliary secretion of cholesterol.
• Oral contraceptive use and pregnancy increase risk due to estrogen effects.
• Obesity, metabolic syndrome, and rapid weight loss are strongly associated with increased biliary cholesterol secretion.
• Gallbladder hypomotility predisposes to gallstones.
• Pregnancy, rapid weight loss, and spinal cord injury can cause hypomotility.

Risk Factors Table Summary: Cholesterol Stones

• Advancing age
• Female sex hormones
• Female sex
• Oral contraceptives
• Pregnancy
• Obesity and insulin resistance
• Rapid weight reduction
• Gallbladder stasis
• Inborn disorders of bile acid metabolism
• Dyslipidemia syndromes

Risk Factors Table Summary: Pigment Stones

• Chronic hemolysis (e.g., sickle cell anemia, hereditary spherocytosis)
• Biliary infection
• Gastrointestinal disorders: ileal disease (e.g., Crohn disease), ileal resection or bypass, cystic fibrosis with pancreatic insufficiency

Pathogenesis: Cholesterol Stones

• Bile formation eliminates excess cholesterol from the body.
• Cholesterol is rendered water-soluble by aggregation with bile salts and lecithins.
• Supersaturation occurs when cholesterol concentrations exceed solubilizing capacity.
• Cholesterol crystallizes out of solution when supersaturation occurs.
• Gallstone formation is enhanced by hypomobility and mucus hypersecretion.
• Hypomobility promotes crystal nucleation.
• Mucus traps crystals, enhancing aggregation into stones.

Pathogenesis: Pigment Stones

• Pigment stones are made up of insoluble calcium bilirubinate salts.
• They form when bile contains a high concentration of unconjugated bilirubin.
• Conditions that cause high concentration of unconjugated bilirubin are chronic red cell hemolysis and biliary tract infections.
• Cirrhosis and Crohn disease are also associated with pigment gallstones.
• In cirrhosis, reduced bile salt synthesis hinders solubilization of bilirubin.
• In Crohn disease, there is increased concentration of bilirubin likely due to altered enterohepatic cycling of bilirubin.

Clinical Features

• Gallstones may be asymptomatic for decades.
• 70-80% of individuals with gallstones never develop symptoms.
• Individuals may experience right upper quadrant or epigastric pain, often excruciating, which may be constant or spasmodic.
• Such pain is caused by gallbladder or biliary tree obstruction or by inflammation of the gallbladder itself.
• Pain often follows a fatty meal that induces gallbladder contraction, pressing a stone against the gallbladder outlet.
• More severe complications include empyema, perforation, fistulas, inflammation of the biliary tree, cholestasis, and pancreatitis.
• Smaller stones or "gravel" are more dangerous as larger stones are unlikely to enter the cystic or common ducts to produce obstruction.
• A large stone may erode directly into an adjacent loop of small bowel, generating intestinal obstruction (gallstone ileus).
• Gallstones are an important risk factor for carcinoma of the gallbladder.