Toxic and Metabolic Diseases of the Liver

Question 1

why does the liver receive a lot of absorbed toxins, bacterial by-products, and orally administered drugs?

Answer 1

first-pass clearance

Question 2

what is the major site of bioactivation (biotransformation)?

Answer 2

liver

Question 3

what is bioactivation/biotransformation?

Answer 3

rendering drugs more water-soluble to increase their secretion by kidney or gall bladder

Question 4

how does conversion to more polar metabolites often occur?

Answer 4

via cytochrome P450 system

Question 5

what is the most common site of hepatotoxicity?

Answer 5

centrilobular necrosis

Question 6

what causes periportal necrosis?

Answer 6

toxins that do not require bioactivation

Question 7

when can chronic hepatic injury occur?

Answer 7

repeated exposures: long term grazing toxic plants, long term drug use

Question 8

what is jaundice?

Answer 8

hyperbilirubinemia

Question 9

what is edema and ascites from?

Answer 9

hypoproteinemia and portal hypertension

Question 10

what are some hepatotoxins?

Answer 10

xylitol
blue-green algae/microcytin
fungal: alfatoxins
plants: pyrrolizidine alkaloids
mushrooms

Question 11

what does microcystin LR do?

Answer 11

disorganization hepatocytes and endothelial cytoskeletal proteins
disruption shape/integrity: necrosis
massive hepatic necrosis

Question 12

what does 8,9-epoxide do?

Answer 12

binds to DNA and proteins of hepatocytes

Question 13

what may be the most common cause of liver disease in general equine practice and cattle?

Answer 13

plants: pyrrolizidine alkaloid toxicity

Question 14

what is phase II of hepatic metabolism?

Answer 14

conjugation: UDP glucuronyl transferase and glutathione

Question 15

what are the differential diagnoses for centrilobular necrosis?

Answer 15

toxin that undergoes bioactivation by cytochrome P450
hypoxic injury: anemia

Question 16

what causes periportal necrosis?

Answer 16

toxins that do not require bioactivation: metal salts

Question 17

what describes an intrinsic hepatotoxin?

Answer 17

predictable, dose related, reproducible
high incidence of injury in expose individuals

Question 18

what describes an idiosyncratic hepatotoxin?

Answer 18

non-predictable, less dose related, may be delayed
occur in very small proportion of exposed individuals

Question 19

what does xylitol cause in the liver?

Answer 19

acute, centrilobular to massive hepatic necrosis
widespread hemorrhage

Question 20

what produces microcystin LR?

Answer 20

Microcystis aeruginosa (cyanobacteria)

Question 21

what do Aspergillus sp and Penicilium sp produce?

Answer 21

alfatoxin B1

Question 22

what is alfatoxin B1 converted to?

Answer 22

8,9-epoxide
this binds to DNA and proteins of hepatocytes

Question 23

what is megalocytosis?

Answer 23

increase in nuclear and cytoplasmic size

Question 24

what does dehydropyrrolizidine alkaloid from pyrrolizidine alkaloids do?

Answer 24

inhibits mitosis in hepatocytes: replacement by fibrosis and bile duct hyperplasia

Question 25

how does pyrrolizidine alkaloid toxicosis present?

Answer 25

acute manifestation of chronic disease

Question 26

what do amanitins (from some mushrooms) do?

Answer 26

inhibit mRNA synthesis: inhibits protein synthesis massive hepatocellular necrosis

Question 27

what type of necrosis does vitamin E/selenium deficiency cause?

Answer 27

hepatosis dietetica centrilobular to massive hepatic necrosis

Question 28

what are the three possible causes of copper toxicity in sheep?

Answer 28

high copper ingestion low molybdenum impaired copper excretion

Question 29

what is the most common presentation for lysosomal storage diseases?

Answer 29

neurological disease

Question 30

what can amyloidosis lead to?

Answer 30

liver rupture and hemoabdomen

Question 31

why is biotransformation sometimes bad?

Answer 31

can lead to bioactivation: free radicals

Question 32

which phase of hepatic metabolism may result in highly reactive intermediates?

Answer 32

phase 1: conversion to more polar metabolite

Question 33

what leads to massive necrosis?

Answer 33

higher dose or highly toxic mushroom blue-green algae

Question 34

what are the outcomes of acute hepatotoxicity?

Answer 34

cell death, hemorrhage, fatty degeneration may be rapid regeneration if stromal framework survives

Question 35

what happens in chronic hepatic injury?

Answer 35

hepatocellular loss, fibrosis, nodular regeneration usually with inflammation

Question 36

what is the mechanism of intrinsic hepatotoxins?

Answer 36

conversion to reactive metabolites: free radicals

Question 37

what are the mechanisms of idiosyncratic toxins?

Answer 37

hypersensitivity related toxic metabolite-dependent: phase I metabolism excessive generation

Question 38

what does NAPQI (highly toxic metabolite of acetaminophen) binding to hemoglobin lead to?

Answer 38

methemoglobinemia

Question 39

how do animals get exposed to alpha toxins?

Answer 39

contaminated food or waste

Question 40

what is seen in subacute/chronic cases of alpha toxin?

Answer 40

fatty degeneration bile duct hyperplasia fibrosis

Question 41

what are some plants with pyrrolizidine alkaloid toxicity?

Answer 41

Senecio jacobaea and vulgaris Crotalaria spp Heliotropium spp

Question 42

what can be seen in the blood with pyrrolizidine alkaloid toxicity?

Answer 42

hyperammonemia (hepatic encephalopathy) hypoproteinemia (generalized edema)