18.3 Flashcards
what is the morphology associated w/ toxicity due to acetaminophen use
massive necrosis (hepatocellular necrosis)
CYP P450 makes toxic metabolite in acinus zone 3. In severe injury the zone injury extends to the periportal hepatocytes → acute hepatic failure
what is the morphology associated w/ toxicity due to anabolic steroid use
bland hepatocellular cholestasis w/o inflam (cholestatic);
peliosis hepatis: blood filled cavities, not lined by endothelial cells (vascular lesion)
hepatocellular adenoma
what is the morphology associated w/ toxicity due to aspirin
(reye syndrome) - microvesicular steatosis (diffuse small droplets fat)
what agents are associated with the development of
hepatocellular adenoma
HCC
cholangiocarcinoma
angiosarcoma
Hepatocellular adenoma: oral contraceptives, anabolic steroid
HCC: EtOH, thorotrast
Cholangiocarcinoma: thorotrast
Angiosarcoma: thorotrast; vinyl chloride
what is the pathogenesis of alc related liver dz
alcohol is a major cause of liver dz in western countries and often leads to death and disability early in life
alc dehydrogenase in the cytosol usually metabolize alc
in high levels - the ethanol-ozidizing system (CYP2E1) located in the SER plays a role –> the alc competes w/ other metabolites and delays the catabolism of other drugs and potentiate its defects
how does steatosis present in alc related liver dz
hepatomegaly w/ minimal symptom; mildly increased bili
how does steatohepatitis present in alc related liver dz
tender hepatomegaly, +/- cholestasis, increased bili;
ast:alt 2:1 (<300-400), increased ALP, nonspecific sxs
how does steatofibrosis/cirrhosis present in alc related liver dz
hepatic dysfxn seen via labs, hypoproteinemia, coag abnormalities: activation of sinusoidal stellate cells and portal fibroblasts → fibrosis
what determines long term survivial for alc liver dz
Survival is up 90% if you stop drinking and don’t have jaundice, ascites or hematemesis
but if continued it drops to 50-60%
Pts w/ advance dz die from hepatic coma, massive GI hemorrhage, intercurrent infxn, hepatorenal syndrome and HCC.
what are the symptoms of acute alcoholism
associated w/ CNS effects but could lead to hepatic and gastric changes
reversible if stopped drinking
how does chronic alcoholims present
affects the liver and stomach but also the GI tract, CNS, CV, pancreas. Liver is the main site of chronic injury.
The alimentary tract can be affected too
B1 def and cause peripheral neuropathy and wernicke-korsakoff syndrome - risk of many other nutrition deficits as well.
Cerebral atrophy, cerebellar degeneration, optic neuropathy.
CV injury is in the myocardium and may cause dilated congestive cardiomyopathy.
risk for acute/chronic pancreatitis
if pregnant the baby is in danger of fetal alcohol syndrome.
increased risk for oral, esophagus and liver CA and also breast CA in women.
what are the criteria for metabolic syndrome
what is NAFLD
how can it progress
MC CLD in USA
more prevalent in hispanics
NAFLD entails the presence of hepatic steatosis in pts who do not drink or do not have other causes that could lead to 2ndary hepatic steatosis.
associated w/ metabolic dz
how does NAFLD present histologically
>5% hepatocytes - fat droplets accumulate
NASH, which has significant overlap with the histology of alcoholic hepatitis
NAFLD presents differently in children, who may have more diffuse steatosis and portal fibrosis and ballooned hepatocytes may not be present
what can help determine the clinical management of NAFLD
Fibrosis –> around central V as “spider webs’ ‘ of pericellular collagen deposition (it’s also referred to as chicken wire pattern) - seen on trichrome stain
can progress to bridging fibrosis and then cirrhosis
Cirrhosis is often subclinical for years and the steatosis/ballooned hepatocytes may be reduced/absent
what is cellular mechanism of hemochromatosis
Iron abs is regulated by hepcidin (encoded by HAMP gene, produced and secreted by the liver). The adult form of hemochromatosis is due to HFE gene mutation, MC C282Y
