Hepatic Toxicants

Question 1

Where can our pets get into too much iron?

Answer 1

vitamins, fertilizers, and slug/snail baits

Question 2

Clinical Signs of Iron Toxicity

Answer 2

vomiting, diarrhea, stomach ulcers

Question 3

Iron Toxicity MOA

Answer 3

not enough ferritin and transferrin, results in free iron which gets into liver, heart, brain, and more, increases free radicals

Question 4

First Organ System Affected by Iron Toxicity?

Answer 4

gastrointestinal (GI)

Question 5

Iron Overdose Treatment

Answer 5

emesis, then magnesium hydroxide (Maalox) to form iron hydroxides which is poorly absorbed so less gets to the liver; also Desferal to protect the liver to get rose wine urine

Question 6

Antidote to Iron Overdose?

Answer 6

Desferal (deferoxamine)

Question 7

Acetaminophen Clinical Signs

Answer 7

methemoglobinemia, tachycardia, tachypnea, weakness, lethargy, face/paw edema, hypothermia, vomiting, death

Question 8

Methemoglobinemia

Answer 8

chocolate/muddy brown blood and mucous membranes

Question 9

Acetaminophen Toxicity Treatment

Answer 9

emesis, activated charcoal and cathartic, N-acetylcysteine, fluids

Question 10

Can you give Cimetidine to cats?

Answer 10

NO!! It inhibits cytochrome p450 which is a cat’s only way to convert

Question 11

Antidote for acetaminophen toxicity?

Answer 11

N-acetylcysteine!

Question 12

NAC (N-acetylcysteine)

Answer 12

precursor to glutathione, binds directly to NAPQI, decreases half-life of methemoglobin

Question 13

Are ferrets sensitive to acetaminophen?

Answer 13

yep, just like cats! (obligate carnivores)

Question 14

NAPQI

Answer 14

metabolite of acetaminophen that causes centrilobular liver necrosis

Question 15

Xylitol affects what species?

Answer 15

DOGS and only dogs

Question 16

Are all 5-carbon sugar alcohols a problem?

Answer 16

no, only xylitol (others include sorbitol, mannitol, etc)

Question 17

Clinical Signs of Xylitol Poisoning

Answer 17

high insulin, hypoglycemia, leads to liver failure
(also vomiting, depression, weakness, ataxia, seizures/coma, diarrhea, cramping, hypokalemia, hypernatremia)

Question 18

Can you treat xylitol with activated charcoal?

Answer 18

no, it doesn’t bind

Question 19

Primary treatment for xylitol ingestion?

Answer 19

dextrose

also small frequent meals and liver protectants, monitor blood glucose

Question 20

Pyrrolizidine Alkaloid Plants

Answer 20

essentially weedy, wild, yellow or blue flowers and seed pods

ragwort, groundsel, fiddleneck, rattlebox

Question 21

Pyrrolizidine Alkaloids MOA

Answer 21

hepatic P450s make toxic pyrroles, react with macromolecules, alkylation of DNA, and then hepatocytes grow but can’t divide (hepatomegaly) and body tries to repair with fibrosis

Question 22

Species most sensitive to Pyrrolizidine Alkaloids?

Answer 22

pigs (but uncommon)

Question 23

Species where we see most Pyrrolizidine Alkaloid toxicity?

Answer 23

cattle and horses (these plants grow pretty wild in the west)

Question 24

Clinical Signs of ACUTE Pyrrolizidine Alkaloid Toxicity

Answer 24

hepatic failure, anorexia, depression, icterus, ascites

Question 25

Clinical Signs of CHRONIC Pyrrolizidine Alkaloid Toxicity

Answer 25

overall unthrifty, photosensitive, icteric Horses: Walla Walla Walking Disease, Missouri Bottoms Disease (circling, head pressing) Cattle/Pigs: chronic liver failure and hard liver disease

Question 26

3 pathognomonic Lesions for Pyrrolizidine Alkaloid Toxicity

Answer 26

1. Hepatocytomegaly 2. Fibrosis 3. Bile Duct Proliferation

Question 27

Treatment for Pyrrolizidine Alkaloid Toxicity

Answer 27

not really... give fluids, laxative, high protein/low carb diet

Question 28

Clinical Signs Cycad and Sago Palm Toxicity

Answer 28

[bloody] vomit, depression, anorexia, hyperbilirubinemia --> liver failure

Question 29

3 Toxins in the Palms

Answer 29

1. Cycasin (GI irritation and hepatic necrosis) 2. BMAA (neurotoxic AA) 3. Unidentified (Parkinson's like)

Question 30

Toxin in Palms that affects dogs?

Answer 30

cycasin

Question 31

Toxin in Palms that affects cattle?

Answer 31

BMAA

Question 32

Amatoxins

Answer 32

found in mushrooms; inhibits RNA polymerase interfering with transcription and translation, eventually breaking down cell membranes in the liver

Question 33

3 Phases of Clinical Signs in Amatoxin

Answer 33

1. GI Signs 2. The Honeymoon 3. Hepatic failure, abdominal pain, seizures, encephalopathy, coma, death

Question 34

Treatment for Amatoxins

Answer 34

emesis, activated charcoal, aspirate the gallbladder, NPO, give OCTREOTIDE

Question 35

octreotide

Answer 35

main treatment for amatoxin mushrooms (blocks carrier molecule OATP1B3 so amatoxins cannot leave the gallbladder)

Question 36

2 Syndromes of Blue Green Algae

Answer 36

1. Acute hepatotoxicosis 2. Acute neurotoxicosis

Question 37

Blue Green Algae MOA

Answer 37

microcystin causes hyperphosphorylation of cytoskeletal proteins leading to disorganization of actin and cellular collapse, eventually causing intrahepatic hemorrhage and death

Question 38

Clinical Signs of Blue Green Algae

Answer 38

weakness, stupor, prolonged CRT, pale MM, bloody diarrhea, coma, tremors, seizures, hypovolemic shock --> hemorrhage and liver failure

Question 39

Blue Green Algae Prognosis?

Answer 39

poor

Question 40

Aflatoxins

Answer 40

aspergillus, in crops with high energy content (corn, peanuts, cottonseed, rice, sweet potaters)

Question 41

How are aflatoxins eliminated?

Answer 41

bile, urine, feces, eggs, milk

Question 42

Acute Aflatoxin Signs

Answer 42

massive liver necrosis and death

Question 43

Chronic Aflatoxin Toxicity Signs

Answer 43

reduced weight gain, rough hair coats, anemia, jaundice, anorexia, depression, ascites, elevated hepatic enzymes

Question 44

Aflatoxin Lesions

Answer 44

diffuse fatty liver, distorted liver, bile duct proliferation, granules and vacuoles in hepatocytes

Question 45

Screening for Aflatoxins

Answer 45

test, also blacklights

Question 46

Can aflatoxins lead to carcinogenesis?

Answer 46

yes

Question 47

Prevention of Aflatoxins

Answer 47

prevent crop damage dry corn (15% moisture or less) clays (bind and make less toxic) ammoniation of feedstuffs

Question 48

Kojic Acid

Answer 48

metabolite of aspergillus that causes problems