Pathology 2 Flashcards
What are the mechanisms of drug and toxin related liver injury?
direct hepatocyte toxicity - acetaminophen, Amanita phalloides, mushroom
Hepatic injury induced inflammation - alcohol
Hepatic conversion of drugs to active toxins
immune mediated injury - granulomatous
What are examples of dose dependent drug toxins to liver?
acetaminophen
chemo
Amanita toxin
What are examples of idiosyncratic drug toxins to liver?
antibiotics
isoniazid
What are the different patterns of vascular disease in the liver?
sinusoidal obstruction syndrome = veno-occlusive disease - chemotherapy, bush tea
Budd-Chiari syndrome = hepatic vein thrombosis - OCPs
Peliosis hepatis - anabolic steroids and tamoxifen
What are the different patterns of tumors in the liver?
hepatic adenoma - OCPs, anabolic steroids
HCC - aflatoxin, thorotrast
cholangiocarcinoma - thorotrast
angiosarcoma - thorotrast, vinyl chloride
What are the 3 different kinds of alcoholic liver disease?
steatosis = fatty liver - 90-100% heavy drinkers
alcoholic hepatitis/steatohepatitis - 10-35%
progressive livery injury and dev of cirrhosis - 8-20% of those who dev steatohepatitis
HCC in 3-6% of alcoholic hepatitis
What effects lead to the development of alcoholic steatosis?
hepatocytes take up fatty acids that alcohol mobilizes from adipocytes - fatty acid oxidation is reduced and assembly and secretion of lipoproteins by VLDL impaired
What is theorized to cause most of the deleterious effects of alcohol on the liver?
acetaldehyde and its metabolites - induce lipid peroxidation, bind to proteins, affect tubulin –> Mallory bodies, mitochondria and membranes, ROS formed
How is alcohol metabolized by the liver?
degraded by alcohol DH, p450, and catalase
What are the histopathologic features of alcoholic steatohepatitis?
steatosis, ballooning degeneration, hepatocyte dropout/necrosis, Mallory bodies (int filaments), inflammatory infiltrates, fibrosis
What are the histopathologic features of alcoholic cirrhosis?
indistinguishable from other forms of end stage
steatosis and mallory bodies lost
What are non alcoholic steatosis and NASH associated with?
“metabolic syndrome” - obesity, type II diabetes, HTN, dyslipidemias, insulin resistance
What mechanisms cause accumulation of triglycerides in hepatocytes in NAFLD?
impaired oxidation of fatty acids
increased synthesis and uptake of fatty acids
decreased hepatic secretion of VLDL
What are two things that NAFLD/NASH can cause?
cryptogenic cirrhosis
incidental elevated aminotransferases
What are the serologic features of autoimmune hepatitis?
primarily in women
autoantibodies - anti nuclear, anti smooth muscle, anti liver/kidney microsomal, soluble liver/liver-pancreas antibodies, elevated IgG
What does the histologic picture of autoimmune hepatitis look like and what are important exceptions?
like chronic viral hepatitis
prominent interface hepatitis and plasma cell rich inflammatory infiltrate
What are causes of secondary hemochromatosis?
parenteral iron overload from transfusions and renal failure
ineffective erythropoiesis - beta thalassemia, sideroblastic anemia, myelodysplastic syndrome
increased oral intake
chronic liver disease
What lab findings are present in hemochromatosis?
elevated transferrin saturation (>50%)
hepatic iron index (2 is primary hemochromatosis)
What is alpha1antitrypsin?
serine protease inhibitor, esp neutrophil elastase
synthesized in liver
How is accumulated AAT visible?
eosinophilic, globular material in lysosomes in cytoplasm of hepatocytes
PAS+
What other conditions are adults with primary hemochromatosis at risk for?
HCC endocrine insufficiency cardiac disease arthritis skin pigmentation
Where does copper accumulate in Wilsons?
liver and brain, cornea (Kayser-Fleischer rings), kidneys, bones, joints, endocrine glands, urine, look for glycogenated nuclei
What are hemangiomas?
single, localized tumors of benign vascular channels separated by collagenous stroma
What is focal nodular hyperplasia?
mass with characteristic, stellate, fibrous scar radiating from center out - separates nodules of benign hepatocytes - bands of fibrous tissue have abnormal vessels
What is a hepatic adenoma?
no portal tracts, sheets of normal hepatic cords with isolated arteries
risk of hemoperitoneum due to rupture
mutations in Wnt pathway have risk for HCC
associated with hormone use in women
What are bile duct adenomas?
single, small lesions of proliferation of small ductules due to local response to previous injury
What are bile duct microhamartomas?
= von Myenberg complexes
multiple, small, dilated bile ducts in expanded portal tracts
What is the epidemiology of HCC?
high incidence and low incidence geographic areas - male to female ratio higher in high incidence
prevalence increases with age except in high incidence due to vertical transmission of hep B
What are the risk factors for HCC?
cirrhosis
hep b and c
hepatocarcinogens - thorotrast, aflatoxin
genetic susceptibility
What is a marker used to diagnose HCC and monitor therapy?
alpha fetoprotein when elevated
What is the fibrolamellar variant of HCC?
in younger patients - not associated with cirrhosis or other risk factors
better prognosis
What are cholangiocarcinomas?
malignant epithelial tumors (adenocarcinomas) derived from bile ducts
intra or extra hepatic
What are conditions associated with cholangiocarcinoma?
chronic biliary tract inf - liver flukes, thorotrast exposure, primary sclerosing cholangitis, fibrocystic diseases of bile ducts
What is the histologic appearance of cholangiocarcinomas?
well-formed glands in abundant fibrous stroma
may produce mucin
jaundice early
more capacity for spread than HCC
What syndromes can be caused by bone marrow transplants?
graft vs. host --> ductopenia, hepatitis siunsoidal obstruction (veno-occlusive) from pre-transplant chemotherapy regimens nodular regenerative hyperplasia - nodules atrophy intervening parenchyma w/o fibrosis
What syndromes can liver transplants cause?
– Host-versus-graft disease – Acute cellular (T cell mediated) • Hepatitis • Endothelialitis • Portal inflammation with bile duct destruction – Chronic rejection • Ductopenia (vanishing bile duct syndrome) • Obliterative arteriopathy
What are extra-hepatic causes of portal vein obstruction/occlusion?
pylephlebitis from thrombosis of portal vein in hilum of liver (portal hilar adenopathy)
hypercoagulable states
propagation of splenic vein thromboses (pancreatitis)
What are intra-hepatic diseases that can affect portal circulation?
cirrhosis
malignancies invading portal vein
sickle cell crises, DIC with sinusoidal occlusion
hepatoportal sclerosis - affects small vein branches w/o association with cirrhosis
What histologic feature is seen with hepatic infarcts?
bland coagulative necrosis - dual blood supply
What is hepatic vein thrombosis/Budd Chiari syndrome?
acute occlusion - liver swollen with tense capsule and mottled red/purple parenchyma
ascites
centrilobular fibrosis with chronic = cardiac cirrhosis
What are causes of Budd Chiari syndrome?
Polycythemia vera Factor deficiencies Tumors Pregnancy Hormones
What are the causes of sinusoidal obstruction syndrome/veno-occlussive dz?
chemotherapeutic agents (bone marrow transplant) toxins
What is the HELLP syndrome?
seen in pregnancy associated liver dz
hemolysis, elevated liver enzymes, low platelets
complicates eclampsia - periportal hemorrhage and necrosis from fibrin depo in first zones
What are pregnancy associated liver dzs?
HELLP syndrome acute fatty liver - fulminant hepatic failure and encephalopathy hepatic vein thrombosis cholestasis severe acute inf with hep E
What kinds of abnormalities is Reyes syndrome associated with?
mitochondrial enzyme deficiencies
