Cholelithiasis

Question 1

Classification of gall stones

Answer 1

1. Based on chemical composition
   *Cholesterol stones :
   ~Pure cholesterol-
   crystalline cholesterol monohydrate+ calcium Bilirubinate + calcium carbonate
   ~ Mixed cholesterol- mixture of cholesterol+ CC + CB +mucin Glycoprotein

• Pigment gall stones : increased unconjugated bilirubin
  ~ Black pigment stones: India, very low cholesterol + CB + CC + mucin Glycoprotein
  ~ Brown pigments stones: Asia, cholesterol <20%+ CB + Ca palmitate+ mucin + FA
  ( Ca phosphate + carbonate - not present)

2. Based on location:
   * intrahepatic - brown pigment stones
   * gallbladder- cholesterol + black
   * Choledocholithiasis (bile duct stones): mixed cholesterol

Question 2

Risk Factors for Gall stones

Answer 2

1. Cholesterol stones.
   ~ increasing age
   ~ female gender: oestrogen increases cholesterol, decrease secretion of bile acids —> lithogenic bile secretion
   ~ pregnancy: slow gallbladder emptying- stasis - precipitation of cholesterol
   ~ oral contraceptives: increase, uptake and synthesis of cholesterol
   ~ environmental factors: increase secretion of cholesterol in bile
   drugs like (clofibrate, octreotide, ceftriaxone), obesity, rapid weight, loss, diet rich
   ~ acquired disorders:Gall bladder stasis
   ~ genetic predisposition
   ~ hereditary: familial - ABCG5 + ABG2 genes
   ~ metabolic abnormalities- diabetes, hyperlipoproteinemia, PBC
2. Pigments stones
   ~ Increasing age
   ~ demography- Asians, rural
   ~ chronic haemolyses
   ~ chronic biliary tract infections
   ~ GI : illeal disease (crohn), ileal resection, cystic fibrosis, pancreatic insufficiency
   ~ alcoholic cirrhosis
   ~ pernicious anaemia

Question 3

Pathogenesis of cholesterol stones

Answer 3

Complex multifactorial process
1. Supersaturation of cholesterol
~ cholesterol is secreted as vesicles or micelles
~ vesicles: cholesterol surrounded by layers of phospholipid bilayer , no bile salts
~ Unilamellar vesicle: cholesterol + 1phospholipid bilayer
~ multilamellar vesicle: cholesterol+ >1 phospholipid bilayer
~ Micellation : vesicle —> complex, aggregate of water soluble molecules
~ mixed micelles- bile acids+ phospholipid+ cholesterol
~ lipophilic portions towords Centre, hydrophilic towards periphery
~ supersaturation: cholesterol concentration of bile > solubility in bile —> lithogenic

~ increased cholesterol secretion: obesity, rich diet, clofibrate, pregnancy, OCP
~ decreased bile salts: crohns, PBS
~ decreased phospholipid( lecithin): MDR-3 mutation

2. Gallbladder hypomotility
   ~ Gall bladder Stasis - aggregation of cholesterol crystals- biliary sludge
3. Nucleation and precipitation
   ~ Unilamellar cholesterol fuses with multilamellar vesicles - Cholesterol monohydrate crystals
   ~ accelerated in litogenic bile
   ~ accelerating nucleation; mucin, calcium, non-mucin Glycoproteins, infection
   ~ antinucleating factors: apolipoproteins, lecithin, Glycoproteins
4. Growth to stone sized aggregates.
   ~ biliary sludge: suspension of cholesterol monohydrate+calcium Bilirubinate in bile
   ~ can resolve, persist or progress
   ~ microlithiasis: crystallisation- Cholesterol monohydrate- microstones- US/ birefringent
   ~ Gall Stone: microstones increase in size- macroscopic

Question 4

Pathogenesis of Pigment stones

Answer 4

1. Black pigment stones
   ~ increase production of unconjugated bilirubin- precipitate as calcium biliruninate
   ~ nidus of mucinous glycoproteins
   ~ causes of increased unconjugated bilirubin: chronic haemolyses (beta thalassaemia, hereditary spherocytosis, sickle cell disease) cirrhosis,ileal dysfunction, pancreatitis
2. Brown pigment stones.
   ~found in gallbladder/ biliary tree
   ~2* to infection and stasis
   ~ bacterial infection- E.coli, Parasitic- ascaris lumbricoides, Clonorchis sinensis
   ~ Bacterial enzymes:
3. Beta glucoronidase : hydrolyse conjugated to unconjugated insoluble BiliRubin
4. Phospholipase : hydrolyse phospholipids- release free fatty acids
5. Hydrolyse bile salts - free, unconjugated bile acids
   ~ these combine with calcium- water insoluble, calcium Bilirubinate - brownstone

Question 5

Morphology of cholesterol stones

Answer 5

~ site: only gallbladder
*Pure Cholesterol: 10%
~ single, pale yellow, round to ovoid
~ granular, hard external surface
~ Large: 2-4 cm
~ cut surface: glistening, long, thin, radiating cholesterol monohydrate crystals
~ radiolucent

• mixed gall stones: more common
  ~ multiple, grey white to black, round or faceted
  ~ small:0.2-3 cm
  ~ cut surface: laminated, dark core
  ~ more cholesterol- radiolucent, more calcium carbonate- radio opaque

Question 6

Morphology of pigment stones

Answer 6

~ Site:
Black :sterile gallbladder bile, Brown:infected intrahepatic or extrahepatic ducts

1. Black stones.
   ~ pure calcium Bilirubinate + other calcium salts
   ~ multiple, shiny black
   ~ irregular, spiculated, moulded, crumble on touch
   ~ small: 0.2-1.5 cm
   ~ radio opaque
2. Brown stones.
   ~ calcium salt of unconjugated bilirubin+ no calcium carbonate/phosphate
   ~ multiple, dull Brown
   ~ laminated , soft, soap, like greasy consistency
   ~small:0.2-1.5 cm
   ~ radiolucent

Question 7

Clinical features and complications of stones in gallbladder

Answer 7

Clinical features
~ asymptomatic
~ inflammation
~ obstruction into cystic duct/CBD
~ Biliary colic- constant, long-lasting

Complications
1. In gallbladder
~ Cholecystitis- acute and chronic
~ empyema of gallbladder- pus
~ hydrops of gallbladder- clear, watery fluid
~ mucocele- cloudy mucoid
~ perforation of gall bladder
~ carcinoma of gallbladder

2. In the bile duct
   ~ biliary obstruction
   ~ acute cholangitis
   ~ acute pancreatitis
3. In the intestine
   ~ biliary fistulas- between biliary system and Bowel/ gallbladder and skin
   ~ gall stone ileus/ Bouverets syndrome- gall stone erodes loop of small intestine- intestinal obstruction