Transcript Diseases of gallbladder

Diseases of gall bladder
Drawing of the normal embryologic development of the gallbladder and bile ducts illustrates the
foregut (A), the cranial end of the hepatic diverticulum, which represents pars hepatica (B) and the
cystic diverticulum (C). The ventral (D) and dorsal (E) pancreas are also demonstrated.
Normal gallbladder histology. The undulating mucosal epithelium overlies a delicate lamina and
only one smooth muscle layer.
No muscularis mucosae .No submucosa.
Normal physiology
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Bile excretion is normally 500-1000 ml/day
Bile is concentrated 5-10x via active absorption of electrolytes accompanied
by passive movement of water
CCK causes gallbladder contraction and release of stored bile 50ml into gut
Bile is critical for intestinal absorption of dietary fat, but NOT the gallbladder.
Bile is 2/3 bile salts, bicarbonate rich, has 3% organic solutes.
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Bile salts: cholates, chenodeoxycholates, deoxycholates, lithocholates, are
highly effective detergents, solubilize water-insoluble lecithin secreted by
the liver
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Lecithin (phosphatidylcholine): hydrophobic, non-aqueous;
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95% of secreted bile salts is reabsorbed in ileum and returned to liver via
portal blood, called enterohepatic circulation of bile salts.
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Cholesterol is eliminated by loss of 0.5 g of bile salts per day
Congenital Anomalies
• Congenitally absent/Agenesis
• Duplication
• Aberrant location (partial or complete
embedding in liver substance)
• Foulded fundus creating phrygian cap
• Hypoplastic narrowing of biliary channels
Abnormal position
Left sided (with or without situs inversus), intrahepatic (5%), retroperitoneal,
suprahepatic; also within falciform ligament, lesser sac or abdominal wall.
Agenesis (absence)
Usually no cystic duct either
Associated with choledocholithiasis, duodenal atresia and other congenital anomalies
No clinical significance
Cysts
May begin as pseudodiverticula (Rokitansky-Aschoff sinuses) with progressive occlusion
of communication with gallbladder
Diverticula
Solitary, 6 mm to 8 cm
Rarely are congenital anomalies with all 3 layers of gallbladder wall
Usually pseudodiverticula (Rokitansky-Aschoff sinuses) with incomplete muscular wall;
due to cholelithiasis or cholecystitis
Heterotopia
Also called ectopia or choristoma
Normal tissue in abnormal location
Usually incidental
Includes liver; gastric ,pancreatic heterotopia with acinar tissue, rarely islets, that may
cause acute pancreatitis in gallbladder
Gastric Hetrotropia
Pancreatic hetrotropia
Hourglass gallbladder
Divided by central constriction
Variant of transverse septate gallbladder
Usually acquired, due to septum of inflamed fibrous tissue or adenomyomatous
hyperplasia
Hypoplasia
Associated with extrahepatic biliary atresia
Micro gallbladder
Defined as less than 2-3 cm long, 0.5 -1.5 cm wide
Associated with idiopathic neonatal hepatitis, alpha-1-antitrypsin disease, cystic
fibrosis
Multiseptate gallbladder
Congenital or acquired
3-10 communicating compartments lined by columnar epithelium
Stones often present in adults .
Phrygian cap
Inversion of distal fundus into body, to which it may become adherent
Either anatomic variant or acquired abnormality
Present in 5% of cholecystograms.
Wandering gallbladder
Long mesentery or no firm attachment to liver
At risk for torsion.
Figure 18-48 Phrygian cap of the gallbladder; the fundus is folded inward.
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© 2005 Elsevier
Cholelithiasis
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Upto 20% of adult population
Majority is symptom free
90% cholesterol stones
10% pigment stones (bilirubin & calcium)
Cholesterol gallstones.
Pigment gallstones.
Gallstones
prevalence & risk factors
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Cholesterol stones
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European & Americans
Advancing age
Estrogen , oral contraceptives & pregnancy
Obesity & metabolic Syn
Rapid weight reduction
Gallbladder stasis ;neurogenic or hormonal
D19H is
1. ABCG5 & ABG2 gene variant
( ATP-binding cassette transporters).
8. Inborn disorder of bile acid metabolism
9. Hyperlipidemia
Pathogenesis of cholesterol stones
Only 10% are pure (at least 90% cholesterol), the
remainder are mixtures with at least 60%
cholesterol by weight
1. initially bile supersaturation with cholesterol
occurs,
2. Cholesterol monohydrate precipitates when no
longer soluble in bile; (initial crystallization),
3. Accelerated cholesterol nucleation in the bile
4. then stone growth facilitated by bile stasis
hypomotility of GB
5. & mucin hypersecretion
four contributing factors for cholelithiasis:
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supersaturation,
cholesterol crystal nucleation,
gallbladder hypomotility,
and accretion within the gallbladder mucous
layer.
Gallstones
prevalence & risk factors
• Pigment stones
– Asian >Westerners - rural>urban
– Chronic haemolytic syndromes
– Biliary infection
– G.I. disorder;
• ileal disease (crohn),
• ileal resection or bypass,
• cystic fibrosis with pancreatic insuffiency
Pathogenesis of pigment stones
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Composed of calcium salts of unconjugated bilirubin.
Black stones associated with (increased unconjugated bilirubin in
bile) Composed of calcium bilirubinate, calcium salts &
mucin glycoprotein
• older age,
• chronic hemolysis,
• cirrhosis,
• sclerosing cholangitis
• severe ileal dysfunction or bypass
Brown (not black) stones associated with infected bile (usually E.
coli).
• Microbial glucuronidase hydrolysis bilirubin glucuronide,
• Ascaris lumbricoides or schistosoma liver fluke
Cholecystitis
• Acute cholecystitis
– Calculus
– Acalculus
• Chronic cholecystitis
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AIDS-related,
emphysematous,
eosinophilic,
follicular,
gangrenous,
granulomatous,
malakoplakia,
porcelain gallbladder,
xanthogranulomatous
Acute cholecystitis
morphology
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GB usually enlarged & tense
Discolored by subserosal hemorrhage
GB wall thickened, edematous & hyperemic.
Serosa covered by fibrin or suppurative coagulative
exudative.
Calculous cholecystitis shows obstructing stone in neck
of gall bladder or cystic duct.
Empyema GB lumen contains pure pus.
Gangrenous cholecystitis GB transformed into necrotic
green-black organ.
Emphysematous cholecystitis clostridia & choliforms.
Acute cholecystitis
clinical features
• Acute Calculous cholecystitis
– Right upper quardrant or epigastric pain.
– Fever,anorexia,tachycardia,sweating,N/V
– Leukocytosis ↑ ALP ,↑ S.bilirubin
– Presentation can be severe sudden or mild
which may resolve spontaneously without
medical intervention
• Acute Acalculous cholecystitis ↑ insidious
but ↑ γ perforation.
I-Acute Calculus Cholecystitis
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90% of cases due to gallstones
50% have bacterial infection
50% of those with jaundice have coexisting choledocholithiasis
Due to chemical irritation inflammation of obstructed GB.
Mucosal phospholipase hydrolyzes luminal lecithin to toxic
lysolecithin
Protective glycoprotein layer is disrupted exposing mucosal
epithelium to detergent action of bile salts
PG released within the wall of distended GB → mural & mucosal
inflammation.
GB dysmotility→ distention & ↑ intraluminal pressure ↓ blood flow to
mucosa
Frequent in DM with gallstones
Acute calculous cholecystitis; the stone was not photographed.
II-Acute Acalculus Cholecystitis
Risk factors
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10% of cases
Sepsis with hypotension & multisystem organ failure.
Immunosuppression
Major trauma & burn
Diabetes mellitis
Infections eg salmonella typhi.
Systemic vasculitis
Severe atherosclerotic ischemia
May be associated with infection by CMV, cryptosporidia or
microsporidia in AIDS patients
• 10-50% mortality
• Cocaine related acute cholecystitis
II-Acute Acalculus Cholecystitis
pathogenesis
• 10% of acute cholecystitis
• Due to ischemia, systemic vasculitis ,severe
atherosclerosis.
• Cystic artery is end artery with no collateral
circulation
• Inflammation & edema of the wall compromising
blood flow
• GB stasis
• Accumulation of biliary sludge (cholesterol
microcrystal).
• Cystic duct obstruction by mucus & viscous bile.
Chronic cholecystitis
• Most cholecystectomies are performed for intermittent obstruction of
gallbladder neck / cystic duct by gallstones, causing biliary colic
• 95% are associated with cholelithiasis
• 75% women, ages 40+
• 1/3 E.coli & enterococci
• Rokitansky Aschoff sinuses
• Procelain gallbladder - dystrophic calcifications
• Xanthogranulomatous – thickened
• Hydrops / mucocele
– Distended gallbladder containing clear and watery (hydrops) or mucoid
secretions (mucocele), instead of bile
– Adult cases almost always due to impacted stones in ampulla or cystic
duct.
Chronic cholecystitis with cholesterol stones. The gallbladder wall is thickened and gray-white,
owing to fibrosis and inflammation. The mucosa is effaced. Multiple faceted cholesterol gallstones
are present within the lumen. The exterior of the specimen is black as a result of India ink
application.
Complication of cholecystitis
• Bactrial superinfection with cholangitis or
sepsis
• GB perforation with local abscess
• GB rupture with peritonitis
• Biliary fistula – intestinal fistula
• Procelain GB ↑ cancer
Extra hepatic Bile ducts
• Choledocholithiasis - stones within bile ducts
• Asian ↑ γ primary which are pigmented stones &
associated with BT infections.
– Complications
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Obstuctive jaundice
Pancreatitis
Cholangitis
Hepatic abscess
Sec biliary cirrhosis
Acute calculous cholecystitis
Ascending cholangitis
Biliary Atresia
• 1:1200 live births
• Within first 3 months of life
• 20% Fetal form due to aberrant
intrauterine development associated with
– malrotation of Ab.viscera ,interrupted IVC
,polysplenia & Cong HD.
• Perinatal form = destruction of normal BT.
Sec to Viral infection & autoimmunity.
Biliary Atresia
Morphology
• Present with neonatal cholestasis
• Intrahepatic bile ducts inflammation &
destruction ,bile duct proliferation ,PT
edema & fibrosis, parenchymal cholestasis
• Cirrhosis develops within 3 to 6 months of
birth.
• Type I common ducts
• Type II hepatic bile ducts
• Type III 90% at or above the porta hepatis
Figure 18-54 Biliary atresia, schematized to show the pattern of biliary tract injury.
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 February 2006 12:33 PM)
© 2005 Elsevier
Choledochal cyst
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Congenital dilation of CBD
Often > 10 yrs age
Present with biliary colic
20 % symptomatic in adulthood.
Caroli disease along with cystic dilatation
of intrahepatic BT
• Complications
– Stone formation, stenosis, pancreatitis,
hepatic biliary obs , carcinoma
Secondary sclerosing
cholangitis
• Much more common than primary sclerosing cholangitis
• Causes: biliary obstruction (choledocholithiasis, post-operative,
chronic pancreatitis, choledochal cyst, extrahepatic biliary atresia),
• infection (immunodeficiency states), toxins, ischemia, malignancy,
other (chronic graft vs. host disease, sarcoidosis, Langerhans cell
histiocytosis, systemic mastocytosis)
• Associated with hepatic lobar atrophy, bacterial infection
• Micro: fibrosis, inflammation, ulceration, foreign body granulomas
• DD: bile duct carcinoma (no lobular pattern of peribiliary glands, no
concentric fibrosis around peribiliary glands, infiltrating glands,
perineural invasion, often marked cytologic atypia)
Primary sclerosing cholangitis
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Chronic cholestatic disorder of unknown origin (possibly autoimmune)
involving entire biliary tract from ampulla of Vater to small intrahepatic bile
ducts or gallbladder
Much less common than secondary sclerosing cholangitis
Rule of 70’s: 70% men, 70% have chronic inflammatory bowel disease
(particularly ulcerative colitis which is usually detected first; only 4% with
ulcerative colitis have primary sclerosing cholangitis, which is unaffected by
colectomy), 70% younger than age 45
Also associated with chronic pancreatitis (15-25%), Riedel’s thyroiditis,
retroperitoneal and mediastinal fibrosis, orbital pseudotumor, Sjogren’s
syndrome, angioimmunoblastic lymphadenopathy
Symptoms: fatigue, pruritis, jaundice
Complications: biliary cirrhosis and liver failure in all cases with median
survival 9-12 years; cholangiocarcinoma (10-43%), colon carcinoma
End stage disease is associated with hyperplasia of glands of extrahepatic
bile ducts, with low incidence of dysplasia and adenocarcinoma,
Carcinoma of extrahepatic bile
ducts
• 90-95% of extrahepatic bile duct
malignancies are adenocarcinomas (bile
duct carcinoma, cholangiocarcinoma)
• Present in 0.5% of autopsies
Tumors of GB
• Benign
– Adenoma
• Tubular
• Papillary
• Tubulopapillary
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Inflammatory Polyp
Adenomyosis,
cholesterol polyp,
granular cell tumor,
hyperplastic/metaplastic polyp,
inflammatory polyp,
villous papilloma
Tumors of GB
• Malignant
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gallbladder carcinoma
carcinoma in situ
clear cell carcinoid,
Ewings/PNET
gastrointestinal stromal tumor,
large cell neuroendocrine carcinoma,
malignant fibrous histiocytoma,
metastases to gallbladder,
mucinous tumor
sarcomatoid carcinoma
small cell carcinoma
squamous cell carcinoma
Carcinoma of GB
• Common in women 7th decade of life
• Gallstone risk factor 0.5% after 20 years
• Infiltrating pattern is more common appear as thickening of GB wall ,
or perforation & fistula formation to adjacent viscera.
• Exophytic pattern grows into the lumen as cauliflower mass.
• Fundus & neck of GB commonest site
• Adenocarcinomas
• Adenosquamous CA
• Carcinoid or carcinosarcoma
• Papillary tumors have better prognosis
• Peritonium, GIT & lung common site of metastasis
Figure 18-55 Gallbladder adenocarcinoma. A, The opened gallbladder contains a large, exophytic tumor that virtually fills the lumen. B, Malignant glandular structures are
present within a densely fibrotic gallbladder wall.
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 February 2006 12:33 PM)
© 2005 Elsevier
Figure 18-55 Gallbladder adenocarcinoma. A, The opened gallbladder contains a large, exophytic tumor that virtually fills the lumen. B, Malignant glandular structures are
present within a densely fibrotic gallbladder wall.
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 27 February 2006 12:33 PM)
© 2005 Elsevier
TNM staging for Carcinoma of gallbladder and cystic
duct
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Primary tumor (T) - carcinoma of gallbladder and cystic duct
TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: Carcinoma in situ
T1: Tumor invades lamina propria or muscular layer
T1a: Tumor invades lamina propria
T1b: Tumor invades muscular layer
T2: Tumor invades perimuscular connective tissue; no extension beyond serosa or into liver
T3: Tumor perforates the serosa (visceral peritoneum) or directly invades the liver or one other
adjacent organ or structure, such as the stomach, duodenum, colon, pancreas, omentum or
extrahepatic bile ducts
T4: Tumor invades main portal vein or hepatic artery or invades two or more extrahepatic organs
or structures
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Regional lymph nodes (N) - carcinoma of gallbladder and cystic duct
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis to nodes along the cystic duct, common bile duct, hepatic artery or portal vein
N2: Metastases to periaortic, pericaval, superior mesenteric artery or celiac artery lymph nodes
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Distant metastasis (M) - carcinoma of gallbladder and cystic duct
M0: No distant metastasis
M1: Distant metastasis