Rose Lou Marie C.

Agbay, MD DPSP
Normal gallbladder histology. The undulating mucosal epithelium overlies a delicate
lamina and only one smooth muscle layer. This is different from elsewhere in the
gut, where two muscle layers exist (muscularis mucosa and muscularis propria).
Congenital Anomalies
 1. Congenitally absent
 2. Gallbladder duplication
 conjoined or independent cystic ducts
 3. Bilobed gallbladder
 presence of longitudinal or transverse septum
 4. Aberrant locations of the gallbladder
 partial or incomplete embedding on the liver substance
 5. Folded fundus
 phrygian cap
 6. Agenesis
 any portion of the hepatic or common bile ducts
 7. Hypoplastic narrowing of biliary channels
 true “biliary atresia”
Congenital Anomalies
 1. Congenitally absent
 2. Gallbladder duplication
 conjoined or independent cystic ducts
 3. Bilobed gallbladder
 presence of longitudinal or transverse septum
 4. Aberrant locations of the gallbladder
 partial or incomplete embedding on the liver substance
 5. Folded fundus
 phrygian cap
 6. Agenesis
 all or any portion of the hepatic or common bile ducts
 7. Hypoplastic narrowing of biliary channels
 true “biliary atresia”
CHOLELITHIASIS (GALLSTONES)

 cholesterol stones
 - 90% of cases
 - crystalline cholesterol monohydrate

 pigment stones
 - bilirubin calcium salts
Pathogenesis of Cholesterol Stones
Four contributing factors for cholelithiasis:
1. The bile must be supersaturated with
cholesterol
- Cholesterol is rendered soluble in bile by
aggregation with water-soluble bile salts
and water-insoluble lecithins

2. Hypomotility of the gallbladder promotes

nucleation

3. Cholesterol nucleation in the bile is

accelerated
- When cholesterol concentrations exceed
the solubilizing capacity of bile
(supersaturation), cholesterol can no
longer remain dispersed and nucleates
into solid cholesterol monohydrate
crystals

4. Hypersecretion of mucus in the gallbladder

traps the nucleated crystals, leading to their
aggregation into stones
Pathogenesis of Pigment Stones
 Pigment gallstones
 complex mixtures of abnormal insoluble calcium salts of
unconjugated bilirubin along with inorganic calcium salts

 Disorders that are associated with elevated levels of

unconjugated bilirubin in bile

1. Hemolytic syndromes
 secretion of conjugated bilirubin into the bile increases
 about 1% of bilirubin glucuronides are deconjugated in the biliary
tree, the large amounts of unconjugated bilirubin produced may
exceed its solubility
2. Severe ileal dysfunction (or bypass)
3. Bacterial contamination of the biliary tree
4. Infection of the biliary tract
 Escherichia coli, Ascaris lumbricoides, O. sinensis
 infection of the biliary tract leads to release of microbial β-
glucuronidases, which hydrolyze bilirubin glucuronides
Cholesterol stones
Pure cholesterol stones are pale yellow, round to ovoid, and have a finely
granular, hard external surface .
Stones composed largely of cholesterol are radiolucent.
 Pigment gallstones
“Black” pigment stones

-contain oxidized polymers of the

calcium salts of unconjugated
bilirubin, small amounts of calcium
carbonate, calcium phosphate, and
mucin glycoprotein, and some
cholesterol monohydrate crystals

- sterile gallbladder bile

- < 1.5 cm in diameter; present in

great number

- contours are usually spiculated

and molded

- radiopaque
 Pigment gallstone
“Brown” pigment stones

-pure calcium salts of unconjugated

bilirubin, mucin glycoprotein, a
substantial cholesterol fraction, and
calcium salts of palmitate and
stearate

- infected intrahepatic or extrahepatic

ducts

- laminated and soft and may have a

soap-like or greasy consistency

- radiolucent
Cholesterolosis
- cholesterol hypersecretion by the
liver promotes excessive
accumulation of cholesterol esters in
the lamina propria of the gallbladder

- mucosal surface – studded with

minute yellow flecks (strawberry
appearance)
 CHOLECYSTITIS

 Acute cholecystitis

 Chronic cholecystitis
Acute Cholecystitis
 Acute calculous cholecystitis
 an acute inflammation of the gallbladder
 90% of cases caused by obstruction of the neck or cystic duct
 primary complication of gallstones
 develops in diabetic patients who have symptomatic gallstones
 most common reason for emergency cholecystectomy

 Acalculous cholecystitis
 cholecystitis without gallstones
 10% of patients with cholecystitis
Acute calculous cholecystitis
-- chemical irritation and inflammation of the obstructed gallbladder

mucosal
disruption of the mucosal epithelium
phospholipases
normally protective exposed to the direct
hydrolyzes luminal
glycoprotein mucus detergent action of bile
lecithins to toxic
layer salts
lysolecithins

prostaglandins released distention and

within the wall of the increased intraluminal
gallbladder dysmotility
distended gallbladder pressure compromise
develops
contribute to mucosal blood flow to the
and mural inflammation mucosa

-- occur in the absence of bacterial infection

-- only later in the course may bacterial contamination develop
Acute calculous cholecystitis
 progressive right upper quadrant or epigastric pain

 mild fever, anorexia, tachycardia, sweating, nausea, and

vomiting

 (-) jaundice

 hyperbilirubinemia
 obstruction of the common bile duct

 mild to moderate leukocytosis

 mild elevation in serum alkaline phosphatase

Acute acalculous cholecystitis
cystic duct
obstruction in the
ischemia
absence stone
formation

 Contributing factors
 inflammation and edema of the wall compromising blood flow
 gallbladder stasis, and accumulation of microcrystals of cholesterol
(biliary sludge), viscous bile, and gallbladder mucus

 Risk factors
 sepsis with hypotension and multisystem organ failure
 immunosuppression
 major trauma and burns
 diabetes mellitus
 infections
Acute acalculous cholecystitis
 clinical symptoms tend to be more insidious
 symptoms are obscured by the underlying conditions precipitating the
attacks

 diagnosis rests on a high index of suspicion

 delay in diagnosis or the disease

 gangrene and perforation

 primary bacterial infection

 Salmonella typhi and staphylococci
Acute cholecystitis  enlarged and tense

 bright red or blotchy, violaceous

to green-black discoloration,
imparted by subserosal
hemorrhages

 serosal covering is frequently

layered by fibrin

 an obstructing stone is usually

present in the neck of the
gallbladder or the cystic duct

 lumen may contain one or more

stones and is filled with a cloudy
or turbid bile that may contain
large amounts of fibrin, pus, and
hemorrhage
Chronic Cholecystitis
 repeated episodes of mild to severe acute cholecystitis

 >90 % of cases associated with cholelithiasis

 supersaturation of bile predisposes to both chronic inflammation

and stone formation

 E. coli and enterococci

 Clinical features:
 recurrent attacks of either steady or colicky epigastric or right
upper quadrant pain
 nausea, vomiting, and intolerance for fatty food
Chronic Cholecystitis
 Serosa
 smooth and glistening
 dulled
 subserosal fibrosis
 dense fibrous adhesion
 sequelae of preexistent
acute inflammation
 Wall
 variably thickened
 opaque gray-white
 Lumen
 fairly clear, green-yellow,
mucoid bile
 stones
Chronic Cholecystitis
--scattered lymphocytes, plasma
cells, and macrophages are found in
the mucosa and in the subserosal
fibrous tissue
--marked subepithelial and
subserosal fibrosis
Rokitansky-Aschoff sinuses
buried crypts of epithelium within the
gallbladder wall
--reactive proliferation of the mucosa
and fusion of the mucosal folds
Hydrops of the gallbladder
Choledocholithiasis
Presence of stones within the bile ducts of the biliary tree

 Associated with...
 pigmented stones
 biliary tract infections

 Asymptomatic
 Symptomatic
(1) obstruction
(2) pancreatitis
(3) cholangitis
(4) hepatic abscess
(5) secondary biliary cirrhosis
(6) acute calculous cholecystitis
Cholangitis
Bacterial infection of the bile ducts

 result of any lesion that creates obstruction to bile flow

 choledocholithiasis
 biliary strictures

 indwelling stents or catheters

 tumors
 acute pancreatitis

 fungi
 viruses
 parasites
Ascending cholangitis
Infection of intrahepatic biliary radicles

 bacteria enter the biliary tract through the sphincter of Oddi

 enteric gram-negative aerobes
 E. coli, Klebsiella, Enterococcus, or Enterobacter
 Clostridium and Bacteroides (mixed infection)

 acute inflammation of the wall of the bile ducts with entry of neutrophils
into the luminal space

 fever, chills, abdominal pain, and jaundice

 suppurative cholangitis
 most severe form
 purulent bile fills and distends bile ducts
Biliary atresia
 a complete or partial obstruction of the lumen of the
extrahepatic biliary tree within the first 3 months of life

 progressive inflammation and fibrosis of intrahepatic or extrahepatic

bile ducts

 major contributor to neonatal cholestasis

 occurs in approximately 1 : 12,000 live births

 single most frequent cause of death from liver disease in early

childhood
 accounts for 50% to 60% of children referred for liver transplantation
 rapidly progressing secondary biliary cirrhosis
Biliary atresia
Two major forms
 Fetal form
 associated with other anomalies
 ineffective establishment of laterality of thoracic and abdominal organ
development
 malrotation of abdominal viscera, interrupted inferior vena cava,
polysplenia, and congenital heart disease
 presumed cause..
 aberrant intrauterine development of the extrahepatic biliary tree

 Perinatal form
 more common
 unknown etiology
 presumed cause...
 viral infection and autoimmunity
 reovirus, rotavirus, and cytomegalovirus
Biliary atresia
 Type I
 disease is limited to the common duct with patent proximal
branches

 Type II
 disease is limited to the hepatic bile ducts with patent proximal
branches

 Type III
 obstruction of bile ducts at or above the porta hepatis
Salient features of biliary atresia
-inflammation and fibrosing stricture of the hepatic or common bile ducts
-periductular inflammation of intrahepatic bile ducts
-progressive destruction of the intrahepatic biliary tree

Liver biopsy
-marked bile ductular proliferation, portal tract edema and fibrosis, and
parenchymal cholestasis
-inflammatory destruction of intrahepatic ducts leads to paucity of bile ducts and
absence of edema or bile ductular proliferation
Biliary atresia
Clinical Features
 Female>Male

 normal birth weight  postnatal weight gain

 normal stools  acholic stools

 serum bilirubin: 6 to 12 mg/dL

 moderately elevated aminotransferase
 moderately elevated alkaline phosphatase

 liver transplantation with accompanying donor bile ducts

 death usually occurs within 2 years of birth

 without surgical intervention
Choledochal cysts
congenital dilations of the common bile duct

 children before age 10

 jaundice and/or recurrent abdominal pain (biliary colic)
 female-to-male ratio is 3 : 1 to 4 : 1

 Consequence...
 stone formation
 stenosis and stricture
 pancreatitis
 obstructive biliary complications within the liver
 bile duct carcinoma
Different types of choledochal cysts. Normal anatomy is illustrated in the left upper frame.
Type I choledochal cyst is most common and is divided into three categories. Illustrated
here is diffuse or cylindrical dilatation of the common bile duct. Type V choledochal cyst is
an intrahepatic bile duct cyst, which may be single or multiple.
Surgically resected type I choledochal
cyst in continuity with the gallbladder
and cystic duct. The lining of the cyst is
hyperemic and contained scant bilious
material.
The lining of a choledochal cyst is eroded
except for a small cleft-like space centrally.
The wall is edematous with scant chronic
inflammation.
Adenomyosis of the gallbladder
 hyperplasia of the muscle layer, containing intramural hyperplastic
glands
CARCINOMA OF THE
GALLBLADDER
 CARCINOMA OF THE GALLBLADDER
 most common malignancy of the extrahepatic biliary tract
 slightly more common in women
 occurs most frequently in the seventh decade of life

 mean 5-year survival rate about 5% to 12% despite surgical

intervention

 gallstones (cholelithiasis)
 most important risk factor (in 95% of cases)

 gallbladders containing stones or infectious

 irritative trauma and chronic inflammation
 carcinogenic derivatives of bile acids
Infiltrating pattern
-more common

-poorly defined area of diffuse

thickening and induration of the
gallbladder wall
-several square centimeters
or may involve the entire
gallbladder

-scirrhous and have a very firm

consistency

-deep ulceration can cause

direct penetration of the
gallbladder wall or fistula
formation to adjacent viscera
into which the neoplasm has
grown
Exophytic pattern
 grows into the lumen as an
irregular, cauliflower mass but
at the same time invades the
underlying wall

 luminal portion may be

necrotic, hemorrhagic, and
ulcerated
 the most common sites of
involvement are the fundus
and the neck; about 20%
involve the lateral walls
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