Toxins

Question 1

What does cocklebur toxicity affect? Most toxic part?

Answer 1

Pigs; seeds/cotyledon

Question 2

Toxic principle of cocklebur?

Answer 2

Carboxyatractyloside inhibits ATP synthesis

Question 3

What does gossypol toxicity affect? Why?

Answer 3

Monogastrics (horses pigs); ruminants detoxify in rumen

Question 4

Toxic principle of gossypol?

Answer 4

Inhibits Glutathione-S-transferase (can’t metabolize things)

Question 5

Other key histo with gossypol?

Answer 5

Skeletal and myocardial necrosis

Question 6

What does aflatoxin affect? Who is least susceptible?

Answer 6

All species; Sheep/cattle

Question 7

How does aflatoxin damage liver?

Answer 7

P-450 dependent metabolism- cytotoxic and mutagenic

Question 8

What associated lesion is aflatoxin associated with?

Answer 8

Cholangiocarcinomas, hepatomas, hepatic carcinomas

Question 9

Toxic principle of aflatoxin

Answer 9

Aflatoxin B1 most toxic, produced by Aspergillus flavus

Question 10

Key histo with aflatoxin

Answer 10

Megalocytes, biliary hyperplasia, fibrosis, nodular regeneration

Question 11

Where do you find pyrrolizidine alkaloids?

Answer 11

Senecio, Crotalaria, Heliotropium plants

Question 12

Toxic principle of pyrrolizidine alkaloids

Answer 12

Dehydropyrrolizidine (DHP) alkaloids produced through P-450 enzymes, bind proteins, amino acids, nucleic acids

Question 13

Most common appearance of pyrrolizidine alkaloid toxicity?

Answer 13

Phasic or chronic, vs. acute

Question 14

Key histo with pyrrolizidine?

Answer 14

Fibrosis, megalocytosis, fuctular reaction, nodular regeneration

Question 15

What breed gets copper toxicosis? Cause?

Answer 15

Bedlington terriers; COMMD1 mutation

Question 16

Other causes of copper toxicity

Answer 16

Altered excretion (in bile), excess intake, low dietary molybdenum and high zinc

Question 17

Stain for copper

Answer 17

Rhodanine, rubeanic acid

Question 18

Key histo for copper toxicity

Answer 18

Centrilobular necrosis and inflammation, golden brown copper granules in cytoplasm

Question 19

Toxic principle for copper

Answer 19

Cu catalyzes free radical formation

Question 20

What produces phomopsin?

Answer 20

Diaporthe toxica fungus, which grows on Lupinus sp.

Question 21

Toxic principle of phomopsin

Answer 21

Phomopsin A and B (mycotoxins) inhibit microtubules, which arrests mitosis in metaphase

Question 22

Key histo with phomopsin

Answer 22

Numerous mitoses

Question 23

What associated conditions occur with phomopsin toxicity in sheep?

Answer 23

Secondary photosensitization

Question 24

Toxic principle of mebendazole?

Answer 24

Idiosyncratic drug reaction- acute hepatic failure even at therapeutic doses

Question 25

What kind of toxin is acetaminophen?

Answer 25

Intrinsic hepatotoxin (dose-dependent)

Question 26

Toxic principle of acetaminophen

Answer 26

Saturates glucuronidation and sulfation detox P450 pathways, so increased formation of NAPQI, which depletes glutathione (GSH)

Question 27

Why are cats more sensitive to acetaminophen?

Answer 27

Less glucuronyltransferase, so can't scavenge metabolites as well

Question 28

Other clinical signs seen in cats with acetaminophen toxicity

Answer 28

Methemoglobinemia, Heinz-body formation

Question 29

Target of zinc toxicity

Answer 29

Pancreas, but also concentrates in hepatocytes, spleen, renal tubular epithelium

Question 30

Other manifestation of zinc toxicity

Answer 30

Heinz body hemolytic anemia

Question 31

Key histo with zinc toxicity

Answer 31

Pancreatic degeneration, necrosis, tubular complexes, fibrosis and loss, ISLETS SPARED

Question 32

What does NSAID toxicity look like in horses? Others?

Answer 32

Right dorsal colitis; gastric ulceration, thrombosis, fibrinoid vascular necrosis

Question 33

Toxic principle of NSAIDs

Answer 33

Decreased COX1 and 2, so decreased PGE2 (mucosal protection), and directly cytotoxic to mucosal/vascular/endothelium

Question 34

Toxic principle of microcystin (blue-green algae)

Answer 34

Microcystin LR cyclic heptapeptide inhibits cytoplasmic protein phosphatases 1 and 2A, causing necrosis of sinusoidal endothelium

Question 35

What does Lantana toxicity do? In what species?

Answer 35

Causes cholestasis in cattle, leading to icterus and photosensitization

Question 36

Toxic principle of Lantana

Answer 36

Pentacyclic triterpenes (Lantadene A)

Question 37

Histo seen with Lantana (three different organs)

Answer 37

Intrahepatic cholestasis, myocardial necrosis, acute renal tubular injury

Question 38

What produces sporidesmin?

Answer 38

Fungus Pithomyces chartarum on ryegrass

Question 39

Toxic principle of sporidesmin

Answer 39

Concentrates in bile, causes oxidative injury and biliary epithelial necrosis

Question 40

Which liver lobe is most affected by sporidesmin?

Answer 40

Left

Question 41

Key histo with sporidesmin

Answer 41

Necrotizing cholangitis, vascular necrosis, bile plugs

Question 42

Key histo with arsenic toxicity

Answer 42

Congestion, submucosal edema, hemorrhage, and ulceration of abomasum