3. BILIARY TRACT
Cholelithiasis (Gallstones)
Cholesterol Stones
• More prevalent in:
1. Industrialized countries
2. Advancing age 20 to cholesterol
3. Caucasian women hypersecretion
4. Pregnancy & oral contraceptive use
• Estrogenic influence inc. expression of hepatic
lipoprotein receptors + inc. hepatic HMG-CoA reductase
activity inc. cholesterol uptake & biosynthesis
5. Gallbladder stasis (neurogenic and hormonal)
4. BILIARY TRACT
Cholelithiasis (Gallstones)
Cholesterol Stones
• More prevalent in:
6. Inborn error of metabolism
a. Impaired bile salt secretion and synthesis
b. Defects in lipoprotein receptors – hyperlipidemia
syndromes
7. Obesity and rapid weight loss increased biliary
cholesterol secretion
5. BILIARY TRACT
Pathogenesis:
Cholesterol conc. > solubilizing
Hepatocellular hypersecretion capacity of bile
of cholesterol SUPERSATURATION
Dec. ability of mucosa to Inc. free cholesterol penetrate
detoxify by esterification GB wall
Dec. responsiveness to GALLBLADDER Stasis
cholecystokinin HYPOMOTILITY
PROMOTE MUCUS ACCELERATED
HYPERSECRETION & CHOLESTEROL CRYSTAL
STONE MICROPRECIPITATION OF NUCLEATION
CALCIUM SALTS
6. BILIARY TRACT
Morphology:
• Cholesterol monohydrate + calcium salts
• Pale yellow, round to ovoid, finely granular
• Pure cholesterol stones radiolucent
• If with calcium carbonate radio-opaque
• Incidental finding of cholesterolosis accumulation
of cholesterol enters within lamina propia of GB
mucosal surface with minute yellow flecks
“strawberry” gallbladder
9. BILIARY TRACT
Pigment Stones
• Increased incidence in:
1. Asians
2. Rural areas
3. Chronic hemolytic syndromes
4. Bacterial contamination of biliary tract
5. GI diseases – ileal disease (e.g. Crohn’s) or bypass
6. Cystic fibrosis with pancreatic insufficiency
10. BILIARY TRACT
Pathogenesis:
• Infection of biliary tract (E. coli, A. lumbricoides,
Opistorchis sinensis) release of microbial -glucuronidase
hydrolysis of B2 increased B1
• Intravascular hemolysis hepatic secretion of B2 (+)
deconjugation in biliary tree increased B1
11. BILIARY TRACT
Morphology:
• Mixture of abnormal insoluble calcium salts of B1 +
inorganic calcium salts
• Two types:
1. Black pigment stones
• Found in sterile GB bile
• Oxidized polymers of calcium salts of B1, calcium
carbonate, calcium phosphate, mucin
glycoprotein and little amount of cholesterol
monohydrate crystals
• Rarely > 1.5 cm diameter
12. BILIARY TRACT
Morphology:
• Two types:
1. Black pigment stones
• Present in greater number; 50% - 75% radio-
opaque; crumble to touch
2. Brown stones
• Found in infected intra- and extrahepatic ducts
• Pure calcium salts of B1, mucin glycoprotein,
substantial cholesterol fraction, calcium salts of
palmitate and stearate
• Laminated and soft with soap-like or greasy
consistency
• Radiolucent
14. BILIARY TRACT
Clinical Features of Gallstones
• 70% - 80% asymptomatic
• May present with biliary pain – excruciating and constant,
colicky most prominent
• Complications:
1. Cholecystitis 6. Obstructive cholestasis
2. Empyema 7. Pancreatitis
3. Perforation 8. Erode into adjacent small bowel
4. Fistula formation loop gallstone ileus
5. Cholangitis 9. Increased risk for CA
15. BILIARY TRACT
CHOLECYSTITIS
Acute Calculous Cholecystitis
• Primary complication of gallstones
• Most common reason for emergency
cholecystectomy
• Precipitated by obstruction of neck or cystic duct
16. BILIARY TRACT
Acute Calculous Cholecystitis: Pathogenesis
OBSTRUCTION Hydrolysis of luminal Production of toxic
lecithins by mucosal lysolecithins
phospholipases
Exposure of epithelium Disruption of
to direct detergent glycoprotein mucus
action of bile salts layer
(+) GB distention & Compromised
(+) GB dysmotility inc. intraluminal mucosal blood flow
pressure
INFLAMMATION
17. BILIARY TRACT
Acute Calculous Cholecystitis: Morphology
Gross:
GB enlarged and tense
Bright red or blotchy; violaceous to green-black (if
with necrosis, called gangrenous cholecystitis
Subserosal hemorrhages
Cloudy or turbid bile fibrin, frank pus, hemorrhage
• If pure pus, called empyema of gallbladder
Microscopic: acute inflammation
19. Histological section of severe acute cholecystitis showing
extensive ulceration of the mucosa, haemorrhage, oedema and a
dense transmural infiltrate of neutrophils and mononuclear
inflammatory cells.
20. BILIARY TRACT
Acute Acalculous Cholecystitis
• Occurs in the absence of gallstones
• Seen in severely ill patients
• Usually occurs in the following circumstances:
1. Post-operative state (major, non-biliary surgery)
2. Severe trauma
3. Severe burns
4. Multi-system organ failure
5. Sepsis
6. Prolonged IV hyperalimentation
7. Postpartum state
21. BILIARY TRACT
Acute Acalculous Cholecystitis: Pathogenesis
• Result from ischemia
• Contributing factors:
1. Dehydration & multiple blood transfusion inc. pigment
load
2. Hyperalimentation & assisted ventilation GB stasis
3. Accumulation of microcrystals of cholesterol, viscous bile
and GB mucus cystic duct obstruction without stone
formation
4. Inflammation and edema of wall compromise blood flow
5. Bacterial contamination and generation of lysolecithins
22.
23. This intraoperative photograph shows a subserosal perforation
of an acute, emphysematous, acalculous cholecystitis in a 58-
year-old diabetic man. He presented with features suggestive of
ileus.
25. BILIARY TRACT
Chronic Cholecystitis
• Associated with cholelithiasis (90%)
• Calculous or acalculous
• Organisms: E. coli and Enterococci
• Symptoms of chronic calculous cholecystitis similar
to the acute form
• Morphology: variable
Subserosal fibrosis
Thickened wall and opaque gray-white appearance
26. BILIARY TRACT
Chronic Cholecystitis
• Microscopic:
Mild cases – lymphocytes, plasma cells, macrophages
Severe cases – subepithelial and subserosal fibrosis
with mononuclear infiltration
Rokitansky-Aschoff sinuses
28. BILIARY TRACT
Chronic Cholecystitis
• Other forms (rare):
1. Porcelain GB
• Extensive dystrophic calcification within GB
• Inc. association with GB carcinoma
2. Xanthogranulomatous cholecystitis
• Shrunken, nodular and chronically inflamed GB with
foci of necrosis and hemorrhage; gallstones usually
present
3. Hydrops of GB
• Atrophic, chronically obstructed GB containing only
clear secretions
30. BILIARY TRACT
Chronic Cholecystitis: Clinical Features
1. Recurrent attacks of steady or colicky
epigastric or RUQ pain
2. Nausea and vomiting
3. Intolerance for fatty foods
31. BILIARY TRACT
Chronic Cholecystitis: Complications
1. Bacterial superinfection cholangitis or sepsis
2. GB perforation and local abscess formation
3. GB rupture with peritonitis
4. Biliary enteric (cholecystenteric) fistula
5. Aggravation of pre-existing medical illness
32. BILIARY TRACT
Tumors of Gallbladder
1. Adenomas
• Benign epithelial localized neoplastic growth of
lining epithelium
• Tubular, papillary or tubulopapillary
2. Inflammatory polyps
• Sessile mucosal projections
• Chronic inflammatory cells & lipid-laden
macrophages
3. Adenomyosis
• Hyperplasia of muscularis with intraluminal
hyperplastic glands
33. BILIARY TRACT
Cancer of Gallbladder
• Women > males; 7th decade
• (+) gallstones in 60% - 90% of cases chronic irritation
and inflammation
• Majority adenocarcinoma; 5% SSCA
• Two forms:
1. Infiltrative
• More common; poorly-defined
• Scirrhous with firm consistency
• Can cause direct penetration of GB wall or fistula
formation to adjacent viscera
34. BILIARY TRACT
Cancer of Gallbladder
2. Exophytic
• Grows into the lumen
• Irregular, cauliflower mass with invasion of
underlying wall
• Most common site of involvement: fundus and neck;
lateral wall (20%)
• With centrifugal invasion of liver at time of discovery
• Common site of seeding: lungs, peritoneum, GIT
37. BILIARY TRACT
Cancer of Gallbladder
• Clinical:
• Indistinguishable from cholelithiasis abdominal
pain, jaundice, anorexia, nausea and vomiting
• Palpable GB
• Features of acute cholecystitis
38. EXTRAHEPATIC BILIARY TRACT
Choledocholithiasis
• Stones within the bile ducts of the biliary tree
• Higher incidence in Asia pigmented stones
• Clinical: usually asymptomatic but may manifest with:
1. Obstruction
2. Pancreatitis
3. Cholangitis
4. Hepatic abscess
5. Secondary biliary cirrhosis
6. Acute calculous cholecystitis
39.
40. EXTRAHEPATIC BILIARY TRACT
Cholangitis
• Bacterial infection of the bile ducts
• Secondary to obstruction to bile flow due to stones
• Other causes:
1. In-dwelling stents or catheters
2. Tumors
3. Acute pancreatitis
4. Benign strictures
5. Infection (viruses, fungi, parasites)
41.
42. EXTRAHEPATIC BILIARY TRACT
Cholangitis
• Pathogenesis: obstruction stasis secondary
bacterial infection enter biliary tract via sphincter
of Oddi
• Organisms: enteric gram (-) aerobes (E. coli),
Klebsiella, Clostridium, Bacteroides, Enterobacter,
group D Streptococci
• Clinical: fever and chills, abdominal pain, jaundice
43. EXTRAHEPATIC BILIARY TRACT
Ascending Cholangitis
• Infection of intrahepatic biliary radicals
Suppurative Cholangitis
• Bile ducts distended and filled with purulent bile
• Most severe form lead to sepsis
44. EXTRAHEPATIC BILIARY TRACT
Biliary Atresia
• Complete obstruction of lumen of extrahepatic biliary tree
within the first three months of life
• Pathogenesis: two forms
1. Fetal form (20% of cases)
• 20 to failure of establishment of laterality of thoracic
and abdominal organ development aberrant
intrauterine development of extrahepatic biliary
tree
• Associated with: malrotation of viscera, interrupted
IVC, polysplenia, congenital heart disease
45. EXTRAHEPATIC BILIARY TRACT
Biliary Atresia
Pathogenesis: two forms
2. Perinatal form
• More common; normally developed biliary tree
destroyed following birth
• Causes:
a. Possible viral infection (Reovirus & Rotavirus)
b. Genetic predisposition
46. EXTRAHEPATIC BILIARY TRACT
Biliary Atresia
Morphology:
Inflammation and fibrosing stricture of hepatic or
common bile ducts
Periductal inflammation of intrahepatic ducts
Obstruction of intrahepatic biliary tree
47. EXTRAHEPATIC BILIARY TRACT
Biliary Atresia
Classification:
Type I – limited to CBD
Type II – CBD + hepatic duct with patent
proximal branches
Type III – 90%; with obstruction of bile ducts at
or above the porta hepatis
Types I and II – surgically correctable
Type III – not correctable; liver transplant
48. Diagram depicting types of
extrahepatic biliary atresia, based on
a classification established by Kasai:
Type I: occlusion of common bile duct
Type IIa: obliteration of common
hepatic duct
Type IIb: obliteration of common bile
duct and hepatic and cystic ducts,
with uninvolved gallbladder and
cystically dilated ducts at porta
hepatis
Type III: obliteration of common,
hepatic, and cystic ducts without
anastomosable ducts at porta hepatis.
(Redrawn from Desmet and Callea.)
49. EXTRAHEPATIC BILIARY TRACT
Biliary Atresia
Clinical:
Female preponderance
Neonatal cholestasis
Normal birth weight and post-natal weight gain
Initially normal stools acholic stools
Serum bilirubin = 6 – 12 mg/dL
Mod. Increased aminotransferase & ALP levels
50. This 3 month old child died with extrahepatic biliary atresia, a disease in
which there is inflammation with stricture of hepatic or common bile
ducts. This leads to marked cholestasis with intrahepatic bile duct
proliferation, fibrosis, and cirrhosis. This liver was rock hard. The dark
green color comes from formalin acting on bile pigments in the liver from
marked cholestasis, turning bilirubin to biliverdin.
51. EXTRAHEPATIC BILIARY TRACT
Tumors:
Choledochal Cysts
• Congenital dilations of CBD
• Children < 10 y/o
• Jaundice + symptoms of biliary colic
• If with cystic dilation of intrahepatic biliary tree
Caroli disease
• Predispose to: stone formation, stenosis & stricture,
pancreatitis
• In older patients, inc. risk of bile duct CA
52. Type I cysts represent approximately 85% of most series. They are
fusiform in shape.
53. Type II cysts represents less than 2% of cases, and are often
called common bile duct diverticulum.
54. Type III cysts also called choledochoceles represents
approximately 2% of cases. Here the dilatation is localized to
the terminal portion of the biliary tract
55. Type IV cysts represent the remaining approximately 10% of
cases. Here the dilatation affects both intrahepatic and
extrahepatic bile ducts
56. Type V cysts are Caroli's disease .They are purely intrahepatic in
nature, and the association with cancer though present is weak than
the rest of the group. They are frequently associated with portal
hypertension and congenital hepatic fibrosis
57. The choledochal cyst was mobilized
and fixed with holding sutures. Clips
are seen in the cyst, which closed the
right and left hepatic ducts.
Resected specimen: The gallbladder
(left) and the deflated bile duct cyst
were removed (right).
Waidner et al. Journal of Medical Case Reports
2008 2:5 doi:10.1186/1752-1947-2-5
58. EXTRAHEPATIC BILIARY TRACT
Tumors:
Cancer of Extrahepatic Ducts
• Insidious; painless, progressively deepening jaundice
• Elderly; men > women
• Risk factors:
1. Primary sclerosing cholangitis
2. Ulcerative colitis
3. Cystic liver disease (Caroli’s dse and choledochal
cyst)
4. Fluke infection (Clonorchis sinensis)
59. EXTRAHEPATIC BILIARY TRACT
Tumors:
Klatskin Tumors
• Tumors arising from the part of the CBD between the
cystic duct junction and the confluence of the R and L
hepatic ducts
• Characteristic features:
1. Slow growth
2. Marked sclerosis
3. Rare distant metastases
60. Type I tumor Type II tumor
involves the affects the main
main hepatic hepatic duct
duct below bifurcation
the bifurcation
Type III tumor Type IV
involves tumors involve
segmental ducts segmental
beyond the ducts in both
primary hepatic liver lobes
duct bifurcation in
one liver lobe
(type IIIa: right
lobe, type IIIb:
left lobe)
62. EXTRAHEPATIC BILIARY TRACT
Tumors: Clinical Features
Jaundice secondary to obstruction
Decolorization of stools
Nausea and vomiting
Weight loss
Hepatomegaly (50%)
Palpable gallbladder (25%)
Inc. serum ALP and aminotransferases
Bile-stained urine
