Toxicology

Question 1

Ethanol metabolism

Answer 1

alcohol dehydrogenase> acetaldehyde -aldehyde dehydrogenase>acetic acid -> CO2 +H2O or ethanol -CYP2E1/NADPH> acetaldehyde -CYP2E1/NADPH> acetic acid

Question 2

Ethanol

Answer 2

coma/death > 0.5%=0.5% 500 mg/dL, liver damage, depletes NAD -> increase lactate and glycerol -> fatty liver, aldehydes more tox - vomiting, hypertension

Question 3

Ethylene glycol

Answer 3

antifreeze ->glycolic acid (toxic) + glyoxylic acid (toxic) -> calcium oxalate (toxic), excreted in urine

Question 4

Ethanol IV

Answer 4

BAC 100-150 mg/mL within 8 hours, saturates ADH. + CA2+, NaHCO3 - supportive = replaces+neutralises

Question 5

Methanol

Answer 5

solvent, paint thinner, GI tract absorption, formaldehyde -ALDH> formic acid (toxic) -folate> CO2 + H2O, 12-24 hour asymptomatic, blindness, acidosis

Question 6

Liver lobule

Answer 6

Central vein, centrolobular (zone 3, high CYP), midzonal (2), periportal (1, high O2, GSH), portal triads

Question 7

Hepatocytes

Answer 7

90% of liver, contain enzymes and cofactors for metabolism and gluconeogenesis+ transaminases (ALT and AST)

Question 8

Kupfer cell

Answer 8

macrophage of liver, zone 1, release O2 and N2 free radicals, can move if needed

Question 9

Endothelial cells

Answer 9

release cytokines and mediators of inflammation when free radicals present, communication network

Question 10

Ito cells

Answer 10

fat storage (glycerol), produce collagen fibres when full (liver cirrhosis)

Question 11

Fatty liver

Answer 11

hepatic fat content >5%, reversible cell death rate, acute hepatotoxins, store fat

Question 12

Cholestasis

Answer 12

impaired ability to form bile/bile duct damage, increased serum levels of bile acids and bilirubin

Question 13

Necrosis

Answer 13

hepatocyte cell death = cant clean up, swelling, leaking of transaminases, influx of inflammatory cells (neutrophils and macrophages)

Question 14

Zonal necrosis

Answer 14

specific zone (centrolobular necrosis)

Question 15

Multifocal necrosis

Answer 15

randomly distributed, single dead cells or clusters

Question 16

Cirrhosis

Answer 16

end stage, fibrous tissue/scars, some regenerating hepatocytes, irreversible, loss of metabolic/detoxifying capabilities

Question 17

Paracetamol hepatotoxicity

Answer 17

centrolobular (high cyp low GSH), ethanol - increase cyp -> increase liver injury (takes time + dose) possible to decrease liver injury

Question 18

Toxicity

Answer 18

parent compound or metabolite, activity and toxicity