Hepatotoxins Flashcards
Meglaocytosis means enlarged _____ with markedly enlarged ____
hepatocytes; nuclei
What does steatophepatits mean?
Fatty liver with inflammation present
What is aka Birch Sugar and is toxic to dogs with the primary targets being the _____ with indirect _____
Xylitol (“Birch sugar”); pancreas with indirect hepatotoxicity
Xylitol MOA:
Stimulation of the pancreas to release insulin in a dose-depend. manner
Clin path findings assoc. with toxicity for Xylitol:
Hypoglycemia, liver enzymes normal if dog can mobilize glycogen to overcome hypoglycemia, otherwise can see increased ALT, AST, GGT within 2-3 hours, later PT and PTT will be increased
Xylitol overall net effect is….
Increased glucose uptake without compensatory glucose production= synthetic hypoglycemia!!!
Profound hypoglycemia and elevated liver enzymes due to inability to buffer glycogen suggests what toxicity???
Xylitol toxicity
Cycad (Sago Palm) is an ornamental plant in tropical US whose seeds are bright _____ and produced by the ___ plant
Orange; female
Cycad (Sago palm) toxic principles:
Glycosides (hepatotoxin)–> cycasin metabolized to methylazoxymethanol and neurotoxin amino acid B meth-L-alanine
MOA of Cycad:
Glucose molecule on cycasin hydrolyzed in gut to yeild sugars and methylazoxymethanol, all sp. affected and time frame of toxicity is acute within 24 hrs
Lab diagnosis of Cycad (Sago Palm):
Increased ALT, ALP, AST, GGT, bilirubin, azotemia, increased PT and PTT bc hepatotoxic so causing prolonged coag., and glucosuria/bilirubinuria/hematuria of the urine
TX of Cycad
Aggressive bc many cases are fatal!! Supportive care, Vit K, SAMe or NAC (antioxidants to help spare liver damage), iv fluids with dextrose
Microcystis aeruginosa–>
A blue green algae, one celled and colonized in clusters of small coccoid cells help together by mucinous secretions. Blooms with nutrient runoff (esp. hos., nitrogen, K+). Warm and sunny conditions
What is the most common cyanotoxin of Microcystis aeruginosa?
Microcystin
Tx of Microcystis aeruginosa:
Detox of the toxin, supportive care, SAMe or NAC (antioxidants), cholestyramine (binds with bile acids in intestine and forms insoluble complexes to prevent reabsorption)
What is aka “Death Angel”???
Amanita phalloides
Amanita phalloides characteristics:
Long white stalk with bulbous base, skirt on upper part of the stalk, white oval cap and found in moist woodlands on east and west coasts under wood (oak)
Toxic principle of Amanita phalloides (“Death Angel”)
Amanitins (not able to be degraded in stomach so of greater concern) and phalloidins (degraded in stomach so little less of concern)
MOA of Amanita phalloides:
Amanitins causing GI mucosal and hepatic injury, reduction of protein synthesis and acute signs presented
Amanita phalloides clinical signs:
GI, hepatic, hepatorenal (progression occurs in that order)
Lab diag. of Amanita phalloides and lesions associated:
Elevated hepatocellular enzymes (ALT, AST), hyperbilirubinemia, urine sample shows amanitins; lesions being massive liver necrosis with icterus, GI issues, and renal tubular acidosis
What are some methods/medications that help remove toxins?
Pen G- interferes with EHR of amatoxins
SAM-e, NPO (limits gall bladder contractions- nothing by mouth), Octerotide (inhibits gall bladder contract), percutaneous biliary drainage (guided by U/S)
Xanthium strumarium (Cocklebur) and Xanthium spinosum (Sheepbur) Characteristics:
Annual, found in moist places in US, have true leaves, seedlings and seeds are in cotyledon stage = toxic!!!
What stage must the X. strumarium/spinosum must be in to be toxic??? Most intoxication is from grazing on plants in this stage.
Cotyledon
As true leaves develop of the bur plants, the toxicity _____
decreases
Cocklebur has two seeds, one germinates in the first growing szn and the other the next. What is the toxin during this phase?
cotyledon stage has Carboxyatractylosides as the toxin
Xanthium strumarium (cocklebur):
- What is the toxic principle?
- What is the MOA???
- What is the toxic part of the plant?
- carboxyatractyloside, burs bad for wool
- glycoside upcouples ox. phosp.which decreases cellular ATP and produces hypoglycemia/hepatic toxicity
- in seed (Cotyledons)
What species are most affected by Xanthium strumarium (cocklebur)???
Pigs, then sheep
Xanthium strumarium (cocklebur) time frame for signs to occur is _____ to ____ -____
12 hours to 2 days after ingestion for signs and symptoms to happen
Pyrrolizidine alkaloid (PA) Plants: are usually _____ and ___ are most sensitive
Bitter; young
Pyrrolizidine alkaloid (PA) Plant the compound itself is not toxic, its the metabolism of the plant. T/F
True!!!
Crotolaria spectabilis (Rattlebox) is a type of Pyrrolizidine alkaloid (PA) Plants: that has this type of annual flower/legume
Yellow pea like flower with alternate simple leaves, oval. Found on roadsides in US
Senecio glabellus (Butterweed, Yellowtop) is a type of Pyrrolizidine alkaloid (PA) Plant that is perennial and has numerous _____ disc flowers in _____ and are seen in what months?
Yellow; clusters; March-June
Senecio jacobaea (Ragwort, Ragweed) is a type of Pyrrolizidine alkaloid (PA) Plant that is biennial and has yellow flowers with a stinking smell, flowers during what months?
June- Nov.
Also found along roadsides, in NW US
What are the toxic parts of PA plants?
Early spring and fall seeds, flowers, and dried forms are the most toxic.
Relative sensitivity to PA- ____ more sensitive than _____. And ____(species) and _____ (species) are most often reported as poisoned. What is the most sensitive species???
Young more than old; horses are cattle; most sensitive is pig
Lesions assoc. with PA toxicosis:
Portal fibrosis, mehalocytosis, bile duct hyperplasia, bile stasis, nodular hyperplasia, hepatocellular necrosis, cirrhosis can often cross placenta and affect fetus, some PA is assoc. with carcinogens
TX of PA toxicosis:
Usually unable to tx very successfully, but can do supportive care of liver issues
Ricinus communis (Castor-Bean) characteristics:
Seeds look like ticks, fruit is capsule shiny
Toxin compound of Ricinus communis (Castor bean) plant is???
Phytotoxin (ricin) which is heat-labile and disrupts protein synthesis, ricin is a select agent used for bioterrorism attacks
What part of the castor bean plant is toxic???
All of it. Seeds are just the MOSTTT toxic
What are the signs of Ricinus communis (Castor bean) plant and lesions associated???
Signs: Colic, emesis, diarrhea. Lesions- seed ingestion will cause severe redness, edema, necrosis of the mucosa of GI tract esp. stomach and small intestines
What is a photosens. occuring secondary to liver disease caused by a toxin?
Hepatic (Type III) photosensitivity rxn
Photosensitization signs and lesions….
occur in 1-3 days, will cause sun burn that turns into exudative vesicles/ulcers and some blindness. Sheep can get ears and face edema= “Big Head”
Sheep can get “Big Head” with _______
Photosensitization
Tetradymia toxin is called ________
Furanosesquiterpenes
Sheep eat _____ when there is nothing else avail. it causes acute death from ____ _____. What occurs with less effected?
Tetradymia; hepatic damage; chronic photosens. (Big Head)
Lantana is a common plant in MS and its toxins are found in what part of the plant? What species is most commonly affected? What lesions does this causse?
folliage and green berries. Grazing ruminants are primarily affected- causes digestive irritation, liver dz, photosens.
Primary photosensation is caused by what 3 plants we discussed in class?
St. John’s wart, Buckwheat, Bishops weed
Primary photosensitization MOA:
Plant molecule goes directly to the surface of the skin and create unstable energized molecules which mesh with other cells and cause free radical release which damage the cell membrane
Fagopyrum esculentum (Buckwheat)
Grown as cover crop for grains, toxic compound is Fagopyrin which is present in the green and dried up plant. Not in the seeds.
St. John’s wort
In eastern US, dots on bottom of the leaves help ID plant, toxic compound is the hypericin which IS THE BLACK DOT
Ammi majus (Bishops Weed)
Toxic compound is psoralens (furocoumarin) and allll parts of the plant are toxic, concentrated in the seeds
