Describe the epidemiology.
Sex: ♀ > ♂ (2–3:1)
Prevalence: approx. 10–20% of the adult population in developed countries
Peak incidence: > 40 years
List general causes.
Imbalance in bile salts, lecithin (stabilizer), cholesterol, calcium carbonate, and bilirubin
Biliary stasis is a key component in gallstone formation.
Impaired gallbladder emptying (e.g., due to bowel rest, prolonged total parenteral nutrition, pregnancy ) → biliary sludge → bile stasis (cholestasis)
List risk factors for cholesterol stones.
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)
Describe the pathophysiology of gallstones (most common stones 95%).
abnormal hepatic cholesterol metabolism → ↑ cholesterol concentration in bile and ↓ bile salts and lecithin → hypersaturated bile → precipitation of cholesterol and calcium carbonate → cholesterol stones or mixed stones
During pregnancy, increased estrogen levels cause increased secretion of lithogenic bile (rich in cholesterol), resulting in the formation of cholesterol gallstones. Increased progesterone levels cause smooth muscle relaxation, decreased and impaired gallbladder contraction, and subsequent bile stasis and formation of gallstones.
Rule of the 6 Fs: Fat, Female, Fertile, Forty, Fair-skinned, Family history.
List risk factors for black pigment stones.
Chronic hemolytic anemias (e.g., sickle cell disease, hereditary spherocytosis)
(Alcoholic) cirrhosis
Crohn disease
Total parenteral nutrition
Advanced age
Describe the pathophysiology of black pigment stones.
↑ hemolysis → increase in circulating unconjugated bilirubin → increased uptake and conjugation of bilirubin → precipitation of bilirubin polymers and stone formation
Describe the risk factors and pathophyisology of mixed/brown pigment stones.
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
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