Chapter 11.5 - Cirrhosis

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What is the pathology here? What characteristics make it so?Alcoholic hepatitis (results from chemical injury to hepatocytes, generally seen with binge drinking) -swelling and ballooning of hepatocytes with necrosis and acute inflammation. -also note the presence of a Mallory body (highly characteristic feature) which are the dark pink accumulations you can see in the hepatocytes. Mallory bodies are damaged intermediate filaments (cytokeratin) -presents with painful hepatomegaly and elevated liver enzymes (AST>ALT...because AST is located in the mitochondria and AST is a mitochondrial poison)What 2 things could cause brown pigment in the hepatocytes?-lipofuscin: a by-product from turnover, normal 'wear and tear' of peroxidized lipids. Seen as the hepatocytes age, kind of like the gray hair of the cell. -iron *distinguish with Prussian blue stain (will show iron)Study the image:brown pigment deposited in hepatocytes - IronStudy the image: what kind of stain is this and what kind of molecule does it stain?Prussian blue stainStudy the image:Describe the primary and secondary causes of hemochromotosis.Primary: AR defect in iron absorption - due to mutations in HFE gene, usually C282Y (cysteine is replaced by tyrosine at amino acid 282). Enterocytes no longer regulate the amount of iron entering the blood. secondary: due to chronic transfusionsWhen does hemochromotosis present and what is the classic triad?-late adulthood classic triad: cirrhosis, secondary diabetes mellitus (damage to islets, 'bronze diabetes'), and bronze skin (iron deposited in skin). *other findings: cardiac arrhythmias and gonadal dysfunction.Wilson's disease is due to _________________________.AR defect in ATP mediated hepatocyte copper transport - results in a lack of copper transport into bile and lack of copper incorporation into ceruloplasmin (molecule that puts copper in the blood)Copper builds up in hepatocytes, leaks into serum and deposits in tissues. What can this cause? When does it manifest and how?-copper mediated production of hydroxyl free radicals leads to tissue damage -presents in childhood with cirrhosis, neurologic manifestations (behavioral changes, dementia, chorea, and Parkinsonian symptoms due to deposition of copper in basal ganglia) Kayser-Fleisher rings in corneaT/F: Hemochromotosis and Wilson's disease both have increased risk for hepatocellular carcinomaTrueWhat is the treatment for hemochromotosis? Treatment for Wilson's disease?H - phlebotomy Wilson's Disease - D-penicillamine (chelates copper)What causes primary biliary cirrhosis? What antibody is a marker of the disease?granulomatous destruction of intrahepatic ducts -classically arises in women (average age 40) -antimitochondrial antibody -presents with features of obstructive jaundice and cirrhosis is a late complication._______ ________ _________ is inflammation and fibrosis of intrahepatic and extrahepatic bile ducts. What is the etiology? How does it present?Primary sclerosing cholangitis -etiology unknown but associated with ulcerative colitis - p-ANCA is often positive. -presents with obstructive jaundice; cirrhosis is a late complication -increased risk for cholangiocarcinomaStudy the image:What pathology is shown here?Primary Sclerosing Cholangitis -note the periductal fibrosis with an onion-skin appearance. -uninvolved regions are dilated resulting in a "beaded" appearance on contrast imaging.What syndrome is fulminant liver failure and encephalopathy in children with viral illness who take aspirin and is likely related to mitochondrial damage of hepatocytes? How does it present?Reye's syndrome -hypoglycemia, elevated liver enzymes, nausea with vomiting; may progress to coma and death_______ ______ is a benign tumor of hepatocytes, associated with oral contraceptive use; regress upon cessation of drug.hepatic adenomaList the 3 risk factors of hepatocellular carcinoma.1. chronic hepatitis (HBV and HCV) 2. Cirrhosis 3. Aflatoxins derived from Aspergillus (induce p53 mutations)What are some causes of cirrhosis?-alcohol, nonalcoholic fatty liver disease, hemochromotosis, wilson's disease, and A1AT deficiency) Alpha 1-antitrypsin (A1AT) is produced in the liver, and one of its functions is to protect the lungs from neutrophil elastase, an enzyme that can disrupt connective tissue (per wikipedia)Hepatocellular carcinoma has an increased risk for Budd-Chiari syndrome how?because hepatocellullar carcinoma can invade the hepatic vein, causing a liver infarction secondary to obstruction -presents with painful hepatomegaly and ascites.What is the serum marker for hepatocellular carcinoma?alpha-fetoproteinWhat is the most common source of metastasis to the liver?-breast, colon, pancreas, and lung.Study the image:Metastatic carcinoma to the liver - clinically may present with a nodular free edge of the liver.