18-3: Drug, Alcohol, and Metabolic Diseases Flashcards
which zone of the lobule is most susceptible to necrosis due to toxic substances
central zone of the lobule -> necrosis of perivenular hepatocytes (zone 3)
with idiosyncratic reactions, which agent is most common in causing liver damage?
antimicrobials
what percentage of alcoholics develop cirrhosis?
10-15 percent so drink on friends.
What P450 enzyme isoform is prevalent in metabolizing alcohol?
CYP2E1
describe clinical features of steatosis
hepatomegaly with minimal symptoms, mildly elevated bilirubin and alk phos
describe clinical features of steatohepatitis
tender hepatomegaly, +/- cholestasis, hyperbilirubinemia, AST:ALT 2:1, elevated alk phos
describe clinical features of steatofibrosis/cirrhosis
labs reveal somatic dysfunction if enough liver tissue left, hypoproteinemia, coag abnormalities
What diseases of the liver are diseases of purely metabolism
NAFLD
Hemochromatosis
Wilson disease
Alpha 1 antitrypsin deficiency
What is the most common cause of chronic liver disease in the US
NAFLD
Define NAFLD
presence of hepatic steatosis in individuals who do not consume alcohol and who do not have another cause of secondary hepatic fat accumulation
-histologically associated with metabolic syndrome
how does pediatric NAFLD differ from adult NAFLD
children show more diffuse steatosis and portal (rather than central) fibrosis, and ballooned hepatocytes may not be present.
what causes hemocromatosis
excessive iron absorption
how does excess iron damage the liver?
1) lipid peroxidation
2) stimulation of collagen by stellate cells
3) interaction of ROS with DNA -> HCC
defect in what gene is responsible for hemochromatosis
HFE gene. Cystine-to-tyrosine 282
confined to caucasian
what are the principle manifestations of hemochromatosis
hepatomegaly abd pain abnormal skin pigmentation deranged glucose or DM Cardiac dysfunction
describe wilson disease
AR disorder caused by mutation of the ATP7B gene
impaired copper excretion into bile and failure to incorporate cu into ceruloplasmin.
what is the age of onset for wilson disease
6-40 y/o with average being 11.4 years
what are some clinical features of wilson disease
neurologic movement disorders
hemolytic anemia
acute and chronic liver disease
how do a1AT deficiency affect the liver
accumulation of misfolded protein in liver
what is the usual function of a1AT
inhibition of proteases (elastase, cathepsin G, proteinase 3) released by neutrophils at sites of inflammation
what is the most common clinically significant mutation associated with a1AT?
PiZ
PiZAT sounds like Pizza. shut up I know yall’s fat asses get it
what about the clinical progression of a1AT makes it the most commonly diagnosed inherited hepatic disorder in children
early presentation
Order the mutation alleles from least to most severe in a1-Antitrypsin deficiency
MM SM ZM SZ ZZ
