Cholelithiasis – etiology, pathogenesis, clinical manifestations, and complications
Cholelithiasis refers to the formation of gallstones within the gallbladder.
Etiology
Risk factors for cholesterol stones (most common type, ~80%)
- Female (estrogen increases cholesterol secretion).
- Obesity, metabolic syndrome.
- Rapid weight loss.
- Pregnancy.
- High cholesterol diet.
- Age >40 years.
- Genetic predisposition (e.g., Native American ancestry).
Risk factors for pigment stones
- Chronic hemolytic anemias (e.g., sickle cell disease).
- Cirrhosis.
- Biliary infections.
- Total parenteral nutrition.
Pathogenesis
Cholesterol stones
- Supersaturation of bile with cholesterol→ cholesterol precipitates as crystals.( too much cholesterol in bile, it exceeds the solubilizing capacity of bile salts and phospholipids.)
- Normally, gallbladder contractions expel bile regularly. Hypomotility of gallbladder (stasis)(e.g., during fasting, pregnancy, TPN), bile stays stagnant → crystals have time toaggregate and grow into stones.
- Mucin hypersecretion (gallbladder epithelium) acts as a scaffold for stone growth(helping crystals stick together and form larger stones)
Pigment stones
- Formed from calcium bilirubinate.
- Occur in conditions with increased unconjugated bilirubin which precipitates and combines with calcium.
- , (e.g., hemolysis )- (e.g., sickle cell anemia → increased breakdown of RBCs → more bilirubin).
- Biliary infections, where bacteria release β-glucuronidase, converting conjugated bilirubin back to unconjugated form → promotes stone formation.
Clinical manifestations
- Often asymptomatic (most patients).
- Biliary colic:
- Sudden RUQ or epigastric pain, often after fatty meals.
- Radiates to right shoulder or back.
- Lasts 30 minutes to a few hours, then resolves as gallbladder relaxes.