Harvey's Garden

Cholelithiasis

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Composition

  • Water: ~97% (primary component).
  • Solutes
    • Bile salts (aka bile acids, 50%): Most abundant solute. Amphipathic derivatives of cholesterol. Emulsify fats for digestion; absorb fat-soluble vitamins (A, D, E, K).
    • Phospholipids (40%): Primarily lecithin. Solubilize cholesterol; prevent cholesterol gallstones.
    • Cholesterol (4%): Bile is the primary route of cholesterol excretion from the body.
    • Bilirubin (2%): Pigment derived from heme catabolism. Gives bile its color. Excreted in bile.
    • Water & Electrolytes: Make up the bulk of bile volume. Gallbladder concentrates bile by absorbing water.
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Etiology

Cholesterol stones (∼ 80% of cases)

  • Radiolucent with radiopaque areas due to calcifications (< 20%)
  • Composed of cholesterol and calcium carbonate
  • Risk factors: Fat, female, forty, fertile
    • Obesity, insulin resistance, dyslipidemia
    • Female sex
      • Estrogen ↑ cholesterol secretion into bile and ↓ bile acid synthesis
      • ↑ HMG-CoA reductase activity
      • 2-3x higher risk than males
    • 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
    • Crohn’s Disease / Terminal Ileum Resection: Disruption of enterohepatic circulation → ↓ bile salt reabsorption. t
    • Rapid weight loss: Mobilization of tissue cholesterol.

Black pigment stones

  • Associated with Chronic Hemolysis (e.g., Sickle Cell, Hereditary Spherocytosis) and Cirrhosis.
  • Mechanism: ↑ Unconjugated bilirubin load precipitates with calcium.
  • Typically Radio-opaque.

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

  • Abdominal Ultrasound (US): Best initial and most accurate test for stones in the gallbladder.
    • Shows hyperechoic foci (stones) with a posterior acoustic shadow.
  • Labs: Typically normal in uncomplicated cholelithiasis. LFTs (ALP, GGT, bilirubin) will be elevated if a stone passes into the common bile duct (choledocholithiasis).
  • For suspected ductal stones (choledocholithiasis):
    • MRCP (Magnetic Resonance Cholangiopancreatography): Excellent non-invasive test to visualize the biliary and pancreatic ducts. Used to confirm suspected CBD stones before proceeding to an invasive procedure. Diagnostic only.
    • ERCP (Endoscopic Retrograde Cholangiopancreatography): Gold standard for both diagnosis and therapy of choledocholithiasis. Allows for sphincterotomy and stone extraction.
    • PTC (Percutaneous Transhepatic Cholangiography): Invasive imaging used when ERCP is unsuccessful or contraindicated. Can also be used for therapeutic biliary drainage.
  • HIDA Scan (cholescintigraphy): Primarily used to diagnose acute cholecystitis (not routine for cholelithiasis); shows non-visualization of the gallbladder.

Treatment

  • Asymptomatic: Observation only.
    • Exception: Porcelain Gallbladder Prophylactic cholecystectomy (high adenocarcinoma risk).
  • Symptomatic (Biliary Colic): Elective Laparoscopic Cholecystectomy.
  • Poor Surgical Candidates: Ursodiol (dissolves cholesterol stones; high recurrence).
  • Choledocholithiasis: ERCP followed by cholecystectomy.
  • Acute Cholecystitis: Early cholecystectomy (within 72 hrs).

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