Disorders of the Gall Bladder and Extra Hepatic Ducts Flashcards
Cholelithiasis (Gallstones) - Epidemiology
- 10-20% of adults in developed countries
- >20 million people in U.S.
- >80% “silent” (asymptomatic)
- 2 types
- cholesterol (80%)
– most common type in Western nations
- pigment (20%)
– more common in non-Western nations
Choleliathiasis - Cholesterol Stones Composition
- Composition: >50% crystalline cholesterol monohydrate
- Pathogenesis:
- cholesterol usually soluble in bile (aggregates with bile salts and lecithins)
- when cholesterol concentrations too high, bile becomes supersaturated and cholesterol precipitates out forming cholesterol monohydrate crystals
- crystals aggregate, forming stones
Cholelithiasis - Cholesterol Stones Contributing Factors
- biliary hypersecretion of cholesterol
- gallbladder hypomotility – promotes nucleation
- altered composition of bile – favors accelerated nucleation of cholesterol crystals
- mucus hypersecretion – traps crystals, thereby promoting aggregation into stones
Risk Factors for Cholesterol Stones
- Native American descent
- increased age
- female sex
- increased estrogen (OCPs, pregnancy)
- obesity, especially after rapid weight loss
- clofibrate (increased biliary excretion of cholesterol)
- gallbladder stasis (e.g. biliary dyskinesia)
- family history
- inborn errors of metabolism (e.g. hyperlipidemia)
- This is a long list…try to at least remember the 4 Fs:
Female, Fat, Forty, Fertile!!
Choleliathiasis - Pigment Stones Composition
- Composition: mostly bilirubin calcium salts
- Pathogenesis:
- infection of biliary tract (bacterial or parasitic) leads to release of microbial beta-glucuronidases, which hydrolyze bilirubin glucuronides, releasing bilirubin OR
- intravascular hemolysis leads to increased biliary excretion of conjugated bilirubin
Choleliathiasis - Pigment STones Risk Factors
•Risk Factors: hemolytic syndromes, bacterial or parasitic infection of the biliary tract (E. coli, Ascaris lumbricoides, Opisthorchis sinensis)
Cholesterol Stones Morphology
- Cholesterol Stones
- Pure cholesterol – pale yellow, round to ovoid, with finely granular, hard external surface; radiolucent
- When mixed with calcium, phosphates, and bilirubin, may be discolored (cut surface gray-white to black) and lamellated; if enough calcium present may be radiopaque
- When multiple may become multifaceted from rubbing against each other
Pigment Stones Morphology
- Black – form in sterile bile; usually small (<1.5 cm) and numerous; soft and friable with speculated, molded contours; often radio-opaque due to high calcium content
- Brown – form in infected intra- and extra-hepatic ducts; laminated and soft with soapy/greasy consistency; radiolucent
Cholesterolosis
•Cholesterol esters accumulate within lamina propria, grossly look like yellow flecks on mucosal surface (“strawberry gallbladder”)
Cholesterolosis in Lamina Propria
Clinical Presentations of Choleliathiasis
- Acute Calculus Cholecystitis
- Acute Acalculus Cholecystitis
- Chronic Cholecystitis
Acute Calculus Cholecystitis
- Most common complication of gallstones
- Results from chemical irritation and inflammation caused by obstruction of gallbladder neck/cystic duct
Acute Calculus Cholecystitis - Signs and Symptoms
o progressive RUQ or epigastric pain
o possible mild fever, anorexia, increased heart rate, diaphoresis, nausea/vomiting
o jaundice suggests a common bile duct obstruction
o physical exam: RUQ tenderness, + Murphy’s sign
o labs: mild increase WBC, possible mild ↑alkaline phosphatase
o “attacks” usually resolve in 24 hrs, sometimes 7-10 days
o up to 25% may develop progressively severe symptoms requiring immediate surgery
o recurrent attacks common
Acute Acalculus Cholecystitis
- No gallstones present; usually occurs in critically ill pts (e.g. after major nonbiliary surgery, severe trauma, severe burns, multiorgan system failure, sepsis, prolonged IV hyperalimentation, post-partum)
- Less commonly may occur in outpatients with vasculitis, atherosclerotic ischemic disease or AIDS
- Related to ischemia due to decreased flow through cystic artery
Acute Acalculus Cholecystitis - Signs and Symptoms
o Much more insidious – difficult to diagnose
o May be no localizing signs/symptoms
o May be fatal if not recognized and treated early!!!
Chronic Cholecystitis
- May or may not be associated with prior attacks
- >90% associated with cholelithiasis
- pathogenesis not well understood
- bacteria (E. coli, enterococci) present in bile in 1/3 of pts
- symptoms: recurrent bouts of steady or colicky RUQ or epigastric pain +/- nausea, vomiting, intolerance for fatty foods
Acute Cholecystitis Morphology
- gallbladder enlarged, tense
- blotchy red and/or green-black discoloration due to subserosal hemorrhages
- fibrinous exudates on serosal surface
- obstructing stone often present in neck/cystic duct
- bile in lumen may be mixed with hemorrhage, pusinfiltration, possible necrosis
Acute Cholecystitis Morphology - Special Cases
- empyema – lumen filled with pus; gallbladder wall thickened, edematous, hyperemic
- gangrenous cholecystitis – gallbladder wall necrotic; prone to perforation
- emphysematous cholecystitis – gas in gallbladder wall due to infection with gas-forming organisms (Clostridia, coliforms); most common in diabetics
Acute Cholecystitis Morphology - Microscopic Changes
•microscopic changes: edema, vascular congestion, leukocytic infiltration, possible necrosis
Chronic Cholecystitis
- changes variable
- serosa usually smooth and glistening
- +/- serosal adhesions from prior bouts of inflammation
- wall thickened (>0.2 cm) and gray-white in color
- bile clear, green-yellow, mucoid, often mixed with stones
Chronic Cholecystitis - Microscopic Changes
•microscopic changes:
- variable inflammation
- subepithelial and subserosal fibrosis
- Rokitansky-Aschoff sinuses (outpouchings of mucosal epithelium through wall)
Chronic Cholecystitis - Special Conditions
- porcelain gallbladder – dystrophic calcification within gallbladder wall; associated with increased risk of cancer
- xanthogranulomatous cholecystitis – gall bladder shrunken and nodular; microscopically see numerous lipid-laden histiocytes with abundant fibrous tissue response
- hydrops – atrophic, chronically obstructed gall bladder filled with clear secretions
Complications – may occur 2o to acute or chronic cholecystitis
- cholangitis and sepsis due to bacterial superinfection
- gallbladder perforation with local abscess formation
- gallbladder rupture with secondary peritonitis
- biliary-enteric fistula/gallstone ileus
- aggravation of previous illness
- choledocholithiasis and related complications
Choledocholithiasis
- at least one gallstone in the common bile duct
- occurs in 10-20% of pts with cholelithiasis
- risk factors include a history of gallstones
- found in 3-10% of patients undergoing cholecystectomy
- may be asymptomatic or may cause symptoms from:
o duct obstruction
o pancreatitis
o cholangitis
o hepatic abscess
o secondary biliary cirrhosis
o calculus cholecystitis
Cholangitis
- bacterial infection of the bile ducts
- bacteria probably enter biliary tract through sphincter of Oddi
- if spreads up into intrahepatic ducts, ascending cholangitis
- usually caused by GNRs (E. coli, Klebsiella, Bacteroides, etc)
- symptoms: fever, chills, abdominal pain, jaundice
- suppurative cholangitis – purulent bile fills bile ducts and extends into hepatic parenchyma resulting in abscesses
- Clinical Triad = CHARCOT’S TRIAD
- Fever
- Jaundice
- RUQ pain
Biliary Atresia
- Extrahepatic biliary atresia – complete obstruction of bile flow due to destruction/ absence of some or all-extrahepatic bile ducts
- most common cause of death from liver disease and most common indication for liver transplant in early childhood
- 2 types:
- fetal (20%) – aberrant intrauterine development of extrahepatic biliary tree
- perinatal (80%) – normally developed biliary tree destroyed shortly after birth
- cause unknown –multiple pathogenetic mechanisms may exist
- symptoms: normal at birth; rapidly develop neonatal jaundice, acholic stools
- Labs: bilirubin usually 6-12 mg/dl at time of presentation
- Morphology: inflammation and fibrosis of bile ducts with small duct proliferation; portal tract edema and fibrosis; cholestasis; cirrhosis develops in 3-6 months if untreated
- fatal within 2 yrs without surgical intervention
- Type III most common – obstruction of bile ducts at or above porta hepatis
Biliary Atresia - Histology
– Inflammation/stricture of hepatic or common bile ducts
– Periductular inflammation and destruction with bile duct proliferation
– Portal tract edema and fibrosis– cholestasis
Choledochal Cysts
•congenital dilatations of the common bile duct; increased risk of bile duct carcinoma
Adenomas
•benign epithelial tumors similar to those seen elsewhere in the gastrointestinal tract
Inflammatory Polyps
•mucosal projections lined by columnar epithelium, with a central stromal core infiltrated by chronic inflammatory cells and lipid-laden macrophages
Adenomyosis
•hyperplasia of the muscularis with intramural hyperplastic glands
Carcinoma - Gallbladder
- Slight female predominance
- Most common in 7th decade
- Stones and/or infection may be risk factors
- Symptoms same as for cholelithiasis
- Usually an incidental finding at surgery; most have invaded liver
- Poor prognosis (1% 5 year survival)
- Morphology:
o 2 patterns of growth
- infiltrating – irregular, diffuse thickening of wall; wall grossly feels firm
- exophytic – irregular, cauliflower-like mass growing into lumen and invading underlying wall
o usually adenocarcinoma, rarely squamous or carcinoid
Carcinoma - Extrahepatic Bile Ducts
- elderly patient presenting with painless jaundice
- slight male predominance
- risk factors: biliary tree fluke infections (Clonorchis sinensis), primary sclerosing cholangitis, IBD, choledochal cysts
- symptoms: painless jaundice, nausea, vomiting, weight loss; hepatomegaly in 50%, palpable GB in 25%
- poor prognosis (mean survival 6-18 months)
- morphology:
o gross: firm gray nodules within bile duct wall
o infiltrative type may cause diffuse wall thickening
o usually adenocarcinoma with variable amount of mucin o extensive fibrosis accompanies epithelial proliferation
o Klatskin tumor – arises at confluence of right and left hepatic ducts; slow growing, very sclerotic, rarely metastasize
Infiltrating Gallbladder Carcinoma
Exophytic Gallbladder Carcinoma
Gallbladder Carcinoma Histology
Klatskin Tumor
