🪨 Cholesterol vs Pigment Gallstone Formation Simulator

Normal Bile — A Balanced Ternary Solution

Healthy bile keeps cholesterol dissolved inside bile salt micelles.

• ~800 mL: Bile produced per day (by hepatocytes)
• 2: Cholesterol carriers (micelles and vesicles)
• ~3 g: Bile salt pool (recycled ~6×/day)
• <1.0: Normal saturation index (undersaturated bile)

The bile solubility triangle

Cholesterol needs bile salts and phospholipids to stay soluble.

Micelle transport

Mixed micelles shuttle cholesterol safely through watery bile.

Enterohepatic recycling

Bile salts are reabsorbed in the ileum and reused.

Cholesterol Supersaturation Begins

Excess liver cholesterol overwhelms the available bile salt supply.

• >1.0: Cholesterol saturation index (supersaturated bile)
• ~3×: Risk multiplier, obesity (higher hepatic cholesterol output)
• ↑ secretion: Estrogen effect (pregnancy, oral contraceptives)
• up to 30%: Rapid weight loss risk (develop gallstones)

Hepatic hypersecretion

The liver pumps out more cholesterol than bile salts can hold.

Gallbladder stasis

Poor emptying lets supersaturated bile linger and concentrate.

Common risk factors

Obesity, rapid weight loss, and estrogen raise cholesterol output.

Cholesterol Monohydrate Crystal Nucleation

Dissolved cholesterol precipitates into microscopic crystal seeds.

• Monohydrate: Crystal type (plate-like cholesterol crystals)
• Pro-nucleating: Mucin gel role (traps crystal nuclei)
• Days–weeks: Nucleation time (before first stone visible)
• >70% cholesterol: Stone composition (defines a cholesterol stone)

Vesicle aggregation

Cholesterol-rich vesicles fuse and crystallize out of solution.

Pro-nucleating factors

Mucin glycoproteins accelerate crystal formation in stagnant bile.

From crystal to stone

Crystals clump together and slowly enlarge into a stone.

Hemolysis or Infection Drives Pigment Stones

Excess bilirubin binds calcium and precipitates as dark pigment.

• Hemolysis / infection: Trigger (sickle cell, cirrhosis, biliary infection)
• Sterile: Black stones (from chronic hemolysis)
• Infected: Brown stones (bacterial deconjugation of bilirubin)
• β-glucuronidase: Key enzyme (unmasks free bilirubin)

Bilirubin overload

Hemolysis floods bile with unconjugated bilirubin pigment.

Calcium binding

Free bilirubin binds calcium to form an insoluble salt.

Infection route

Bacterial enzymes deconjugate bilirubin, seeding brown pigment stones.

A Mature Gallstone Has Formed

Aggregated crystals harden into a single solid gallstone.

• ~10–15%: Prevalence (of adults worldwide)
• ~80%: Cholesterol stones (of all gallstones)
• ~20%: Pigment stones (black and brown types)
• ~20%: Symptomatic rate (of stone carriers)

Cholesterol stone outcome

Yellow-green, layered stones dominate in Western populations.

Pigment stone outcome

Small, dark, brittle stones dominate hemolytic patients.

Clinical significance

Stones can obstruct the cystic or common bile duct.