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11 Cards in this Set

  • Front
  • Back

which hepatoocyte zone is daged most by carbon tetrachloride?

zone 3 necrosis occurs because it is metabolized by CYP2e1 to CCl3, a toxic radical


radicals can be ,metabolized by anti-oxidant molecule to a non-toxic species, but that is phase 2 enzyme biotransformation, of which the is a reduced availability in zone 3

Mtabolism of Ethanol EtOH

ADH and ALDH metabolize ethanol to form acetate


under normal conditions the body can handle this fine


to much ethanol disrupts lipid handling



th increased alcohol consumption, cyp2e1 is induced


yp2e1 metabolized ethanol into reactive species and acetylaldehyde



overwhelms ability of ALDH to metabolize/ detoxicate acetylaldehyde



preferentially damages zone 3

Hepatopathology- liver damage

Steatosis


Steatohepatitis


Fibrosis


Cirrhosis


Cancer

Define Steatosis

fatty liver



caused by dysfunctional regulation of fatty acid production, metabolism, transport in liver


Alcoholism



Can develop into more serious forms of liver damage


more vulnerable to additional toxic insults


Define and describe Steatohepatitis

Steatosis can progress to steatohepititis



signals additional damage to hepatocytes



damaged cells initiate inflammatory response


mediated by kupffer cells in hepatocytes


inflammatory response is mostly there to help the cells


too much information can be harmful

Define and describe liver fibrosis (scar tissue)

inflammation and cell damage triggers a repair mechanism



hepatocytes produce excessive amounts of collagen that forms a scar within the liver




can disrupt the normal function of the hepatocytes and liver


alteration in xenobiotic transport and biotransformation



describe and define cirrhosis

fibrosis can progress to cirrhosis



excessive fibrosis can cause severe liver dysfunction


leads to progressive damage to hepatocytes and liver function


liver failure

describe and define hepatic carcinoma

another end stage of major damage to heatocytes



can progress from steatosis, steatohepatitis and fibrosis



cancerous cells arise from hepatocytes


increased cell turnover


direct interactions with DNA with toxicant or toxic metabolite

What is the relationship between Aflatoxin an liver damage?

toxic metabolite is mycotoxin



its found in contaminated crops


cereals, peanuts, tree nuts, spices



mtabolized by CYP3A4



Metabolite forms DNA adducts


DNA damage, mutation, carcinogenesis

Cyanobacteria and routes of exposure

cyanobacteria are part of algal blooms found in both fresh and marine water



recent increase in algal blooms, domestically and internationally


role of climate change in these processes




produces toxin called microcystin



exposure through contaminated water, oysters/cams/seafood, and recreational activities



cyanobacteria and liver toxicity

microcystin targets liver and inhibits proteins involved in signal transduction in the cell


leads to death of hepatocytes



mcrocystin influxed through SLC transporters



biotransformation occurs through Phase 2 conjugation with GSH