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Toxicology > Hepatotoxicology > Flashcards

Hepatotoxicology Flashcards

1
Q

five main functions of the liver

A 
nutrient homeostasis 
filtration of particulates
protein synthesis
bioactivation and detoxification
formation of bile and biliary secretion
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2
Q

three main organs blood that travels to the liver

A

stomach
spleen
intestines

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3
Q

collect bile and drain into the bile duct

A

canaliculi

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4
Q

structural liver unit

A

hepatic lobule

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5
Q

functional liver unit

A

hepatic acinus

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6
Q

filter out small particles which are digested or encapsulated

A

kupffer cells

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7
Q

accumulate fat materials and other lipids

A

ito cells

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8
Q

how does bile get through the canaliculi

A

the liver cells are able to contract using actin fibers

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9
Q

what is the blood supply into the liver

A

60-70% portal vein

30-40% hepatic artery

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10
Q

why is cholic acid such a good bile salt

A

has a hydrophobic side and a hydrophilic side to form micelles around lipids

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11
Q

when there is secretion into the intestine and then reabsorption back into the portal vein

A

enterohepatic cycling

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12
Q

heme to biliverdin metabolism

A

heme oxygenate using NADPH

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13
Q

biliverdin to bilirubin metabolism

A

biliverdin reductase using NADPH

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14
Q

what color is biliverdin

A

green

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15
Q

what color is biliruin

A

yellow

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16
Q

bilirubin to bile metabolism

A

UDP-glucuronyl transferase

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17
Q

deposits of fat cause liver enlargement

A

fatty liver

18
Q

scar tissue forms more liver cell injury occurs

A

live fibrosis

19
Q

scar tissue makes liver hard and unable to work properly

A

cirrhosis

20
Q

symptoms of liver damage (6)

A 
cell death
canalicular cholestasis 
bile duct damage
sinusoidal damage
fibrosis and cirrhosis
tumors
21
Q

three characteristics of apoptosis

A

necrosis/apoptosis
release of ALT/AST
focal or zonal cell death,

22
Q

characteristics of canalicular cholestasis

A

reduced bile flow

release of bile comp in blood (jaundice)

23
Q

bile duct damage…

A

cholestasis
epithelial inflammation
methylene dianiline (epping jaundice)

24
Q

sinusoidal damage…

A

causes veno-occlusive disease

25
Q

fibrosis and cirrhosis…

A

accumulation of collagen, scar tissue, function impairment, irreversible damage

26
Q

two characteristic of tumors

A

cell type dependent

aflatoxin

27
Q

susceptibility of liver depends on three things

A

high blood flow
high biotransformation activity
storage of essential compounds

28
Q

three places for first step ethanol metabolism

A

microsomes
cytosol
peroxisomes

29
Q

microsomes use what enzyme for ethanol metabolism

A

CYP2E1

30
Q

cytosol/mitochondria use what enzyme for ethanol metabolism

A

ADH

31
Q

peroxisomes what enzyme for ethanol metabolism

A

catalase

32
Q

ethanol is metabolized to ____in the first step

A

acetaldehyde

33
Q

where does the second step of ethanol metabolism take place

A

mitochondria

34
Q

what enzyme is used in the mitochondria for ethanol metabolism

A

ALDH

35
Q

acetaldehyde is metabolized to ____in the mitochondria

A

acetic acid

36
Q

inflammatory response to liver damage with an influx/activation of immune cells

A

hepatitis

37
Q

two ways to get hepatitis

A

viral infections

toxicant induced

38
Q

neoantigen formation

A

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

39
Q

attach actin filaments, collapse of scaffolding, no bile transport in canaliculi

A

phalloidin and microcystin

40
Q

inhibits bile salt explorer

A

cyclosporine A

41
Q

p-glycoprotein inhibitors

A

estrogen glucuronides

42
Q

six causes for cholestasis

A 
impaired uptake
diminished contractility of canaliculus
diminished transcytosis
leaky paracellular junctions
impaired secretion
concentration of reactive species

Toxicology (20 decks)

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