Epidemiology
Etiology
Cholesterol stones (∼ 80% of cases)
- Radiolucent with radiopaque areas due to calcifications (< 20%)
- Composed of cholesterol and calcium carbonate
- Risk factors
- Obesity, insulin resistance, dyslipidemia
- Female sex
- Especially during reproductive years due to increased levels of estrogen and progesterone
- Increased estrogen levels cause increased secretion of bile rich in cholesterol, (lithogenic bile), which can result in the formation of cholesterol gallstones.
- Increased progesterone levels cause smooth muscle relaxation, decreased gallbladder contraction, and subsequent bile stasis with formation of gallstones.
- Multiparity or pregnancy
- Age (> 40 years of age)
- European, Native American, or Hispanic ancestry
- Family history
- Drugs: fibrates (inhibition of cholesterol 7-α hydroxylase), estrogen therapy, oral contraceptives
- Malabsorption (e.g., Crohn disease, ileal resection, cystic fibrosis)
- Rapid weight loss (e.g., after bariatric surgery)
Black pigment stones
- Radiopaque
- Composed of calcium bilirubinate
- Risk factors
- Chronic hemolytic anemias (e.g., sickle cell disease, hereditary spherocytosis)
- (Alcoholic) cirrhosis
- Crohn disease
- Total parenteral nutrition
- Advanced age
- Pathophysiology: ↑ hemolysis → increase in circulating unconjugated bilirubin → increased uptake and conjugation of bilirubin → precipitation of bilirubin polymers and stone formation
Mixed/brown pigment stones
- Radiolucent
- Risk factors: bacterial infections and parasites (e.g., Clonorchis sinensis, Opisthorchis species) in the biliary tract, sclerosing cholangitis
- Pathophysiology: infection or infestation → release of β-glucuronidase (by injured hepatocytes and bacteria) → hydrolyzes conjugated bilirubin and lecithin in the bile → increased unconjugated bilirubin and fatty acids → precipitation of calcium carbonate, cholesterol, and calcium bilirubinate (dark color) in bile
- Unconjugated bilirubin is lipid-soluble and insoluble in water. This insolubility allows it to precipitate with calcium ions, forming calcium bilirubinate. While conjugated bilirubin is water-soluble (bound to glucuronic acid) and remains dissolved in bile, preventing precipitation.
- β-glucuronidase: a lysosomal enzyme that deconjugates direct bilirubin. Present in breast milk and can cause neonatal unconjugated hyperbilirubinemia. Also found in intestinal brush border cells, where it deconjugates direct bilirubin to release indirect bilirubin that is then reabsorbed and recycled. Bacterial β-glucuronidase in the biliary tract is implicated in the pathogenesis of brown pigment gallstones.
Pathophysiology
Clinical features
Diagnostics
Treatment
Nonoperative management of cholelithiasis
Indications
- Patients at high risk of complications due to surgery or anesthesia (e.g., recent myocardial infarction)
- Patients unwilling to undergo surgery
Oral bile acid dissolution therapy
- May be useful in dissolving pure cholesterol stones (i.e., radiolucent stones) that are < 0.5 cm
- Ursodeoxycholic acid
- Duration of therapy: 6–24 months [17][33]