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What causes gallstones?

What Causes Gallstones?

There are four direct causes of gallstones. However, various underlying conditions are risk factors for these causes: (vii.124, 129-130, 133, 135)

Table VII.20: Causes & Risk Factors for Gallstones
Primary Cause Conditions That Promote What Makes the Condition a Risk Factor?
Too Much Cholesterol in Gallbladder Obesity and Other Metabolic Conditions

High insulin levels associated with diabetes and obesity cause: (vii.124)

  • ↑ Synthesis of cholesterol in liver. (vii.124)
  • ↑ Insulin resistance. (vii.130)
  • ↑ Cholesterol secretion from liver. (vii.124)
Hormones

(typically from oral contraceptives or hormone replacement therapy)
  • ↑ Cholesterol secretion from liver (estrogen). (vii.124)
  • ↓ Bile emptying from gallbladder (both estrogen and progesterone). (vii.124)
Genetic
  • ↑ Uptake of cholesterol in liver. (vii.130)
  • ↓ Enzyme activity that produces bile acids. (vii.130)
Rapid Weight Loss & Yo-Yo Dieting
  • ↑ Cholesterol secretion from liver. (vii.130)
  • ↓ Gallbladder contractions and emptying (due to low dietary fat). (vii.130)
Ethnicity
  • American Pima Indians. (vii.124)
  • Chilean women and native Mapuche Indians in Chile. (vii.124, 130)
  • Certain northern European populations. (vii.124)
Dietary Factors
  • ↑ Calorie diets. (vii.124)
  • ↑ Cholesterol, high fat diet (long-term). (vii.124, 133)

Increased Age (vii.124)
 
Too Few Bile Acids/Salts and/or Lecithin Ileal Resection
  • ↓ Circulation of bile acids. (vii.130)
Genetic
  • ↑ Uptake of cholesterol in liver. (vii.130)
  • ↓ Enzyme activity that produces bile acids. (vii.130)
Liver Disease

(cirrhosis of the liver; primary biliary cirrhosis (PBC); other liver dysfunction
that increases estrogen)
  • ↓ Bile acid synthesis. (vii.124)
  • ↓ Gallbladder contraction. (vii.124)
Ethnicity

American Pima Indians. (vii.124)
Cystic Fibrosis

Pancreatic dysfunction leads to reduced circulation of bile acids (in non-obese Caucasians). (vii.124)
Crohn's Disease
  • Pancreatic dysfunction leads to reduced circulation of bile acids (in non-obese Caucasians). (vii.124)
  • Poor absorption of bile salts from colon reduces amount that gets returned to the liver. (vii.130)
 
Gallbladder Dysfunction Dietary Factors Too little fat reduces how much cholecystokinin (CCK) is released. This causes fewer gallbladder contractions and the gallbladder empties poorly. (vii.130)
Infection
  • Inflammation of gall bladder lining causes too much water to be absorbed. What's left behind is a sludge that promotes the formation of gallstones. (vii.133)
  • Scar tissue can cause bile duct obstruction. (vii.124, 136)
Impaired Contraction of Gallbladder
  • Incomplete gallbladder emptying allows the mostly-water bile to turn into sludge. This fosters gallstone formation. (vii.124)
  • Excess gallbladder mucus combines with bile proteins (e.g., from bacteria or bilirubin) and promotes crystallization and gallstones. (vii.124)
 
Nucleation
  • Essential early step in gallstone formation, nucleation is the combining of cholesterol molecules into microcrystals. (vii.135)
  • Solid cholesterol crystals form which then bind to other bile substances to form stones. (vii.135)
A greater risk factor in obese women than in obese men. (vii.130)
Final segment of small intestines. (vii.134)
Such as lecithin phospholipids. (vii.135)

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