Hepatotoxicology Flashcards
five main functions of the liver
nutrient homeostasis filtration of particulates protein synthesis bioactivation and detoxification formation of bile and biliary secretion
three main organs blood that travels to the liver
stomach
spleen
intestines
collect bile and drain into the bile duct
canaliculi
structural liver unit
hepatic lobule
functional liver unit
hepatic acinus
filter out small particles which are digested or encapsulated
kupffer cells
accumulate fat materials and other lipids
ito cells
how does bile get through the canaliculi
the liver cells are able to contract using actin fibers
what is the blood supply into the liver
60-70% portal vein
30-40% hepatic artery
why is cholic acid such a good bile salt
has a hydrophobic side and a hydrophilic side to form micelles around lipids
when there is secretion into the intestine and then reabsorption back into the portal vein
enterohepatic cycling
heme to biliverdin metabolism
heme oxygenate using NADPH
biliverdin to bilirubin metabolism
biliverdin reductase using NADPH
what color is biliverdin
green
what color is biliruin
yellow
bilirubin to bile metabolism
UDP-glucuronyl transferase
deposits of fat cause liver enlargement
fatty liver
scar tissue forms more liver cell injury occurs
live fibrosis
scar tissue makes liver hard and unable to work properly
cirrhosis
symptoms of liver damage (6)
cell death canalicular cholestasis bile duct damage sinusoidal damage fibrosis and cirrhosis tumors
three characteristics of apoptosis
necrosis/apoptosis
release of ALT/AST
focal or zonal cell death,
characteristics of canalicular cholestasis
reduced bile flow
release of bile comp in blood (jaundice)
bile duct damage…
cholestasis
epithelial inflammation
methylene dianiline (epping jaundice)
sinusoidal damage…
causes veno-occlusive disease
fibrosis and cirrhosis…
accumulation of collagen, scar tissue, function impairment, irreversible damage
two characteristic of tumors
cell type dependent
aflatoxin
susceptibility of liver depends on three things
high blood flow
high biotransformation activity
storage of essential compounds
three places for first step ethanol metabolism
microsomes
cytosol
peroxisomes
microsomes use what enzyme for ethanol metabolism
CYP2E1
cytosol/mitochondria use what enzyme for ethanol metabolism
ADH
peroxisomes what enzyme for ethanol metabolism
catalase
ethanol is metabolized to ____in the first step
acetaldehyde
where does the second step of ethanol metabolism take place
mitochondria
what enzyme is used in the mitochondria for ethanol metabolism
ALDH
acetaldehyde is metabolized to ____in the mitochondria
acetic acid
inflammatory response to liver damage with an influx/activation of immune cells
hepatitis
two ways to get hepatitis
viral infections
toxicant induced
neoantigen formation
drug comes into cell
bioactivation and adduct formation
drug protein adducts act as immunogens
forms antibodies which bind to protein adducts in the plasma membranes
attach actin filaments, collapse of scaffolding, no bile transport in canaliculi
phalloidin and microcystin
inhibits bile salt explorer
cyclosporine A
p-glycoprotein inhibitors
estrogen glucuronides
six causes for cholestasis
impaired uptake diminished contractility of canaliculus diminished transcytosis leaky paracellular junctions impaired secretion concentration of reactive species
