Pathology of the GI Tract- Liver and Gallbladder (3) Flashcards
what is the most common morphologic pattern of drug or toxin induced liver injury?
necrosis of perivenular hepatocytes (zone 3) is the typical feature of drug-induced liver injury
what is the most common culprit for idiosyncratic reactions, which are the most common form of drug-induced liver injury ?
antimicrobial drugs
what are the three forms of alcohol related liver disease?
steatosis, steatohepatitis, and steatofibrosis/cirrhosis
how does steatosis present?
hepatomegaly with minimal symptoms, mildly elevated bilirubin and alk phos
how does steatohepatitis present?
tender hepatomegaly, +/- cholestasis, hyperbilirubinemia, AST:ALT 2:1 levels, elevated alk phos
how does steatofibrosis/cirrhosis present?
labs reveal hepatic dysfunction if enough liver tissue left, hypoproteinemia, coag abnormalities
what is NAFLD strongly associated with?
insulin resistance
what is a patient with NASH at risk for developing?
NASH cirrhosis or HCC
where does fibrosis of the liver typically develop?
around the central vein
how does pediatric NAFLD differ from adult NAFLD?
typically children show more diffuse steatosis and portal (rather than central) fibrosis, and ballooned hepatocytes may not be present
how does NAFLD present?
it is typically asymptomatic except for signs and symptoms of metabolic syndrome
what is hemochromatosis caused by?
excessive iron absorption
what is occurring in hereditary hemochromatosis?
regulation of intestinal absorption of dietary iron is abnormal
what is the main regulator of iron absorption?
hepcidin
what gene encodes for hepcidin?
HAMP gene
where is hepcidin produced?
the liver
the adult form of hemochromatosis is usually caused by mutations of what gene?
HFE gene
what is the most common HFE mutation?
a cysteine-to-tyrosine substitution at amino acid 282
which population of people is the HFE mutation most common?
caucasian populations of european origin
what are the principal manifestations of hemochromatosis?
hepatomegaly, abdominal pain, abnormal skin pigmentation, deranged glucose homeostasis or DM, cardiac dysfunction, and atypical arthritis
how is hemochromatosis diagnosed?
very high levels of serum iron and ferritin and liver biopsy or genetic testing screening of family members of probands is important
what stain shows hemochromatosis on histology slides?
prussian-blue stain
what could be the final outcome of hemochromatosis?
cirrhosis or cardiac disease; hepatocellular carcinoma
what is wilson disease?
an autosomal recessive disorder caused by mutation of the ATP7B gene resulting in impaired copper excretion into bile and a failure to incorporate copper into ceruloplasmin
what are the manifestations of wilson disease?
accumulation of toxic levels of copper in many tissues and organs (liver, brain, and eye); hemolytic anemia
what is the age of onset of wilson disease?
6 to 40 years of age
how is the biochemical diagnosis of wilson disease made?
decreased serum ceruloplasmin, increased hepatic copper content, and increased urinary excretion of copper
how does a patient with wilson disease present?
some with acute or chronic liver disease, some may have neurologic involvement (movement disorders or psychiatric symptoms) or hemolytic anemia
what happens when copper is deposited into Descemet’s membrane of the cornea?
it presents as Kayser-Fleischer rings
what is alpha-1-antitrypsin deficiency?
an autosomal recessive disorder of protein folding marked by very low levels of circulating alpha-1 antitrypsin
what is the function of alpha-1-antitrypsin?
it inhibits proteases (particularly neutrophil elastase)
what does alpha-1-antitrypsin deficiency lead to?
pulmonary emphysema and it causes liver disease as a consequence of hepatocellular accumulation of the misfolded protein
what is the most common clinically significant mutation leading to alpha-1-antitrypsin deficiency?
PiZ
when is alpha-1-antitrypsin deficiency diagnosed?
because of it’s early presentation with liver disease, alpha 1 AT deficiency is the most commonly diagnosed inherited hepatic disorder in infants and children
what type of mutation leads to alpha-1 AT deficiency?
a point mutation (glu342–>Lys342)
what are the histologic features associated with alpha-1 AT deficiency?
cytoplasmic globular inclusions in hepatocytes
what are the 3 clinical presentations of alpha-1 AT deficiency?
neonatal hepatitis with cholestatic jaundice; adolescence (hepatitis, cirrhosis, or lung disease); middle to late life (cirrhosis +/- HCC)
