Hepatic Toxicants Flashcards
Where can our pets get into too much iron?
vitamins, fertilizers, and slug/snail baits
Clinical Signs of Iron Toxicity
vomiting, diarrhea, stomach ulcers
Iron Toxicity MOA
not enough ferritin and transferrin, results in free iron which gets into liver, heart, brain, and more, increases free radicals
First Organ System Affected by Iron Toxicity?
gastrointestinal (GI)
Iron Overdose Treatment
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
Antidote to Iron Overdose?
Desferal (deferoxamine)
Acetaminophen Clinical Signs
methemoglobinemia, tachycardia, tachypnea, weakness, lethargy, face/paw edema, hypothermia, vomiting, death
Methemoglobinemia
chocolate/muddy brown blood and mucous membranes
Acetaminophen Toxicity Treatment
emesis, activated charcoal and cathartic, N-acetylcysteine, fluids
Can you give Cimetidine to cats?
NO!! It inhibits cytochrome p450 which is a cat’s only way to convert
Antidote for acetaminophen toxicity?
N-acetylcysteine!
NAC (N-acetylcysteine)
precursor to glutathione, binds directly to NAPQI, decreases half-life of methemoglobin
Are ferrets sensitive to acetaminophen?
yep, just like cats! (obligate carnivores)
NAPQI
metabolite of acetaminophen that causes centrilobular liver necrosis
Xylitol affects what species?
DOGS and only dogs
Are all 5-carbon sugar alcohols a problem?
no, only xylitol (others include sorbitol, mannitol, etc)
Clinical Signs of Xylitol Poisoning
high insulin, hypoglycemia, leads to liver failure
(also vomiting, depression, weakness, ataxia, seizures/coma, diarrhea, cramping, hypokalemia, hypernatremia)
Can you treat xylitol with activated charcoal?
no, it doesn’t bind
Primary treatment for xylitol ingestion?
dextrose
also small frequent meals and liver protectants, monitor blood glucose
Pyrrolizidine Alkaloid Plants
essentially weedy, wild, yellow or blue flowers and seed pods
ragwort, groundsel, fiddleneck, rattlebox
Pyrrolizidine Alkaloids MOA
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
Species most sensitive to Pyrrolizidine Alkaloids?
pigs (but uncommon)
Species where we see most Pyrrolizidine Alkaloid toxicity?
cattle and horses (these plants grow pretty wild in the west)
Clinical Signs of ACUTE Pyrrolizidine Alkaloid Toxicity
hepatic failure, anorexia, depression, icterus, ascites
Clinical Signs of CHRONIC Pyrrolizidine Alkaloid Toxicity
overall unthrifty, photosensitive, icteric
Horses: Walla Walla Walking Disease, Missouri Bottoms Disease (circling, head pressing)
Cattle/Pigs: chronic liver failure and hard liver disease
3 pathognomonic Lesions for Pyrrolizidine Alkaloid Toxicity
- Hepatocytomegaly
- Fibrosis
- Bile Duct Proliferation
Treatment for Pyrrolizidine Alkaloid Toxicity
not really… give fluids, laxative, high protein/low carb diet
Clinical Signs Cycad and Sago Palm Toxicity
[bloody] vomit, depression, anorexia, hyperbilirubinemia –> liver failure
3 Toxins in the Palms
- Cycasin (GI irritation and hepatic necrosis)
- BMAA (neurotoxic AA)
- Unidentified (Parkinson’s like)
Toxin in Palms that affects dogs?
cycasin
Toxin in Palms that affects cattle?
BMAA
Amatoxins
found in mushrooms; inhibits RNA polymerase interfering with transcription and translation, eventually breaking down cell membranes in the liver
3 Phases of Clinical Signs in Amatoxin
- GI Signs
- The Honeymoon
- Hepatic failure, abdominal pain, seizures, encephalopathy, coma, death
Treatment for Amatoxins
emesis, activated charcoal, aspirate the gallbladder, NPO, give OCTREOTIDE
octreotide
main treatment for amatoxin mushrooms (blocks carrier molecule OATP1B3 so amatoxins cannot leave the gallbladder)
2 Syndromes of Blue Green Algae
- Acute hepatotoxicosis
- Acute neurotoxicosis
Blue Green Algae MOA
microcystin causes hyperphosphorylation of cytoskeletal proteins leading to disorganization of actin and cellular collapse, eventually causing intrahepatic hemorrhage and death
Clinical Signs of Blue Green Algae
weakness, stupor, prolonged CRT, pale MM, bloody diarrhea, coma, tremors, seizures, hypovolemic shock –> hemorrhage and liver failure
Blue Green Algae Prognosis?
poor
Aflatoxins
aspergillus, in crops with high energy content (corn, peanuts, cottonseed, rice, sweet potaters)
How are aflatoxins eliminated?
bile, urine, feces, eggs, milk
Acute Aflatoxin Signs
massive liver necrosis and death
Chronic Aflatoxin Toxicity Signs
reduced weight gain, rough hair coats, anemia, jaundice, anorexia, depression, ascites, elevated hepatic enzymes
Aflatoxin Lesions
diffuse fatty liver, distorted liver, bile duct proliferation, granules and vacuoles in hepatocytes
Screening for Aflatoxins
test, also blacklights
Can aflatoxins lead to carcinogenesis?
yes
Prevention of Aflatoxins
prevent crop damage
dry corn (15% moisture or less)
clays (bind and make less toxic)
ammoniation of feedstuffs
Kojic Acid
metabolite of aspergillus that causes problems
