Patterns of liver injury Flashcards
evolution of fatty liver disease
Hepatic steatosis, steatohepatitis, fibrosis/cirrhosis, CA (HCC)
what is metabolic syndrome
central (around waist) obesity, DM 2, HTN, dyslipidemia
What causes macrovesicular fatty liver
nurtritional (obesity, TPN), metabolic (DM, hyperlipidemia), drug-related (EtOH, corticosteroids)
what causes microvesicular fatty liver
pregnancy, Reye’s syndrome, tetracyclines
Lipogranulomas
cause lipoapoptosis. Exposure of non-adipose tissue (heliver) to excess long-chain FAs
PPARalpha
becomes defective/overloaded in fatty liver dz.
PPAR alpha vs gamma
alpha is signaled when fat comes into system and helps burn fat. Gamma stores fat
what pattern of drinking contributes more to liver damage: binge or steady
steady
ADH/ALDH2 pathway of alcohol metabolism
EtOH converted by Alcohol dehydrogenase (ADH) to acetaldehyde (toxic) in the cytosol which aldehyde dehydrogenase (ALDH2) then converts to acetate in the mitochondria.
Mutations in alcohol metabolism
most asians have mutant ADh that metabolizes EtOH faster resulting in acetaldehyde accumulation. ALDH2 mutation in some groups leads to inactivity and acetaldehyde buildup.
CYPs in EtOH metabolism
2E1. Generates ROS which damage hepatocytes and stimulate stellate cells to make collagen
three histo features of alcoholic hepatitis
necrosis, Mallory bodies, PMN infiltration
two major effects of acetaldehyde on liver
stellate cell activation leading to fibrosis. Steatohepatitis by altering metabolism and leading to hepatocyte death