pathogenesis of diseases of the gallbladder and biliary tract
DESCRIPTION
Pathogenesis of diseases of the gallbladder and biliary tract. John J O’Leary. Biliary tract disorders. Disease of intra-hepatic ducts. LARGE DUCT BILIARY OBSTRUCTION, PRIMARY BILIARY CIRRHOSIS, PRIMARY SCLEROSING CHOLANGITIS. LARGE DUCT BILIARY OBSTRUCTION. - PowerPoint PPT PresentationTRANSCRIPT
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Pathogenesis of diseases of the gallbladder and
biliary tract
John J O’Leary
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Biliary tract disorders
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Disease of intra-hepatic ducts
LARGE DUCT BILIARY OBSTRUCTION,
PRIMARY BILIARY CIRRHOSIS,
PRIMARY SCLEROSING CHOLANGITIS
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LARGE DUCT BILIARY OBSTRUCTION
• Usually extrahepatic, rarely intrahepatic at porta hepatis• Causes - gallstones, tumours, strictures, biliary atresia• Effects on the liver:
Acini - perivenular (zone 3) cholestasis Portal tracts - bile duct proliferation at margins of tracts - neutrophil polymorph infiltrate - oedema of connective tissue Sometimes bile “infarcts” and bile lakes (duct rupture)
• Complications: - acute suppurative cholangitis (ascendingcholangitis).
- liver abscesses if untreated - secondary biliary cirrhosis if unrelieved
• Clinical features of cholestatic jaundice
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PRIMARY BILIARY CIRRHOSIS
• A chronic cholestatic disease due to a non-suppurative destructive cholangitis of intrahepatic bile ducts, immune mediated
• F:M as 10:1. Age range 20-80years, peak at 40-50• May be associated with other autoimmune diseases• Very insidious onset, may be asymptomatic for decades, pruritis,
fatigue, xanthelasmas, leading to frank cholestatic jaundice, cirrhosis• 90-95% positive anti-mitochondrial antibodies (AMA) against E2 subunit
of pyruvate dehydrogenase complex inner mitochondrial membrane• Characteristically a granulomatous destruction of bile ducts. Leads to
ductopenia. Copper accumulates in periportal hepatocytes due to chronic cholestasis. Chronic inflammation in portal tracts with interface hepatitis. Portal fibrosis progresses to cirrhosis
• Liver biopsy used to confirm diagnosis and to stage the disease
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PRIMARY SCLEROSING CHOLANGITIS
• A chronic cholestatic disease due to a non-specific inflammatory fibrosis of bile ducts, intrahepatic and extrahepatic
• M:F as 2:1. Affects mostly young men
• 70% have ulcerative colitis. Linkage with HLAB8, DR2, DR3. pANCA+
• May be associated with other rare fibrosing conditions
• May be asymptomatic, pruritis and cholestatic jaundice and then cirrhosis develop over many years
• Concentric fibrosis of bile ducts; may result in a scar at site of duct. Leads to ductopenia. Copper accumulates in periportal hepatocytes. Usually scanty lymphocytic infiltrate. Portal fibrosis progresses to cirrhosis. Liver biopsy used to confirm diagnosis and stage
• 10% at risk of developing cholangiocarcinoma
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MISCELLANEOUS BILE DUCT DISEASES
• Acquired sclerosing cholangitis can occur in a number of conditions including AIDS.
• Bile duct injury can also occur with liver allografts, graft-versus-host-disease (GVHD), viral hepatitis, drugs, toxins, pyogenic infections, parasitic infestations and other rare conditions.
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Disease of extra-hepatic bile ducts
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• Biliary atresia is among several neonatal and childhood disorders such as the fibropolycystic disorders which include congenital hepatic fibrosis and various cystic conditions.
• Cholangitis – acute inflammation of the wall of bile ducts. Can result from obstruction of the biliary tree.
• Choledocholithiasis – presence of gallstones in the biliary tree
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Cholangitis
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Biliary atresia
• Neonatal cholestasis• Occurs in 1:10,000 live births• Complete obstruction of bile flow caused by destruction or
absence of all or part of the extra-hepatic bile ducts• Most likely an acquired inflammatory disorder on unknown cause• Most frequent cause of death from liver disease in early childhood• Features:
– Inflammation and fibrosing stricture of the hepatic or common bile duct
– Inflammation of the major intra-hepatic ducts with destruction– Features of biliary obstruction on biopsy– Peri-portal fibrosis within 3-6 months of birth
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Biliary atresia
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Gall bladder disorders
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Cholelithiasis: gallstones
• Gallstones afflict 10% of the population• 80% of stones are cholesterol stones• Remainder: bilirubin calcium salts [pigment stones]• Risk factors:
– Demography [Europe, N & S America, Mexico]– Advancing age– Female sex– Obesity– Rapid weight reduction– Gallbladder stasis– Hyerlipidaemia– Chronic haemolytic syndromes– Biliary infection– Gastrointestinal disorders: [CD, CF, pancreatic insufficiency]
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Gallstones
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Cholecystitis
• Inflammation of the gallbladder• Acute and chronic• Almost always occurs in association with stones• May get empyema [pus] in the acute phase• Approx. 5-10% of gallbladders removed for acute
cholecystitis do not contain stones• Chronic: results from acute bouts and is commonly
associated with gallstones
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Acute cholecystitis
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Chronic cholecystitis
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Carcinoma of the gallbladder
• Fifth most common cancer of the digestive tract• Most frequently occurs in the 7th decade of life• 5 year survival: 1%• Rarely resectable when found• Gallstones are present in 50-70% of cases• In Asia: parasitic and pyogenic disease associated• Symptoms:
– Abdominal pain, anorexia, jaundice, nausea and vomiting
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Carcinoma of the gallbladder
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Molecular progression of carcinoma of the gallbladder
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2 molecular pathways fordevelopment of gallbladder carcinoma
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Carcinoma of the extra-hepatic bile ducts [including the Ampulla of Vater]
• Cholangiocarcinomas• Extremely insidious onset, painless with progressive
jaundice• Hepatomegaly present in 50% of patients• Distended gallbladder in approx. 25% of patients• Features of extra-hepatic bile duct obstruction
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Carcinoma of extra-hepatic bile ducts