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1 of 124 - Bovine – orange/ Equine – green/ Cat – red/ Dog – Blue / Sheep and Goat - yellow Toxicology Small Animals - Xylitol - o Problem in Dogs. o Rapid release of insulin – monitor for hypoglycemia – due to rapid release of insulin ▪ Vomitin...

1 of 124 - Bovine – orange/ Equine – green/ Cat – red/ Dog – Blue / Sheep and Goat - yellow Toxicology Small Animals - Xylitol - o Problem in Dogs. o Rapid release of insulin – monitor for hypoglycemia – due to rapid release of insulin ▪ Vomiting/ weakness/ ataxia/ depression/ hypokalemia seizures and coma ▪ Why hypokalemia in – storage? o Less commonly hepatic failure ( liver issues) o Treatment: Begin fluids -containing dextrose/ run baseline glucose/ run liver values( coags as well)/ hepatoprotectants if necessary ( SAM – E). - Bleach- o Dilute stomach with milk, DO NOT induce emesis because can cause further damage, GI protectants - Black widow spiders = Latrodectus mactans, L. Hesperus o Acetylcholine is the toxin binds calcium channels – leading to ascending motor paralysis and destruction of peripheral nerves o Recumbent, vocalizing, pain, rigidity with muscle spasms – death from respiratory/ cardiovascular failure - Rodenticides - o Warfarin = anticoagulant – interferes with II, VII, IX, and X ▪ Give Vitamin K1, if chronic give plasma as well ▪ Prothrombin time (PT) will be prolonged soonest after ingestion – because VII has shortest half life and is part of extrinsic system o Brodifacoum = D-con – inhibits epoxide reductase (loss of Vitamin K – interferes with II, VII, IX, and X) ▪ Give Vitamin K, monitor prothrombin time (PT) o Cholecalciferol = gets converted to active Vitamin D to cause increased resorption of calcium and gut absorption of calcium leading to sometimes fatal hypercalcemia - Ethylene glycol - o High anion gap, azotemia, calcium oxalate crystalluria, metabolic acidosis, hyperglycemia, and either polyuria or oliguria (anuria in worst case), hypocalcemia (from chelation of Ca by EG metabolites) o Treatment aimed at alcohol dehydrogenase – give 4- methylpyrazole (4-MP) – does not work in CATS ▪ Ethanol competes with this enzyme when given soon after exposure ▪ 4-MP better than ethanol because doesn’t cause hyperosmolality, metabolic acidosis, CNS depression - Organophosphate - o Inhibit acetylcholinesterase causing muscarinic signs such as hypersalivation, incoordination, and bloat o Treatment = atropine or 2-PAM (pralidoxime – anticholinesterase) - Fleet enemas - o High in phosphorus – leads to decrease in serum calcium due to law of mass action 2 of 124 ▪ Hypernatremia and hyperphosphatemia – due to absorption from the colon ▪ Hypocalcemia leads to weakness, shock, tremors, and seizures o Give calcium gluconate, phosphorus binders, with severe cases of hyperkalemia give insulin and dextrose - Strychnine = snail bait o Competitively antagonizes action of glycine – loss of impulse contractility in the spinal cord and brainstem – affects striated muscle o Give methocarbamol (for convulsions), prevent stimulation - Chocolate = methylxanthines (theobromine, caffeine) o CNS excitation, tachycardia, vasoconstriction o Highest concentration of toxin in unsweetened baking chocolate - Pyrethrins = toxic to CATS, alters activity of sodium ion channels to increase length of depolarization o Depression, hypersalivaiton, ataxia, muscle tremors ! treat with methocarbamol, bathe to remove product - Acetominophen = toxic to CATS o Cats lack glutathione and glucoronyl transferase – leads to methemoglobinemia (dark brown blood – due to oxidative damage to hemoglobin), may also see Heinz bodies o Treatment with N-acetylcysteine - HEINZ BODY ANEMIA = methylene blue, molybdenum deficiency, rye grass, brassica family o Zinc – from pennies minted after 1983 o Onions – can cause hemolytic anemia ▪ HEMOGLOBINURIA and hemoglobinemia – Heinz body anemia due to oxidative damage to RBCs o Red maple leaves = Acer rubrum – HORSES – see icterus (due to low oxygen content of blood), colic - RENAL FAILURE - o Grapes and raisins – o Lillies – ACUTE RENAL FAILURE in cats – toxic ones = Stargazer lily (Lillium family) ▪ Peace – calcium oxalate ▪ Lily of the Valley – cardiotoxin ▪ Day Lilly – Renal toxicity ▪ Easter Lilly – Renal toxicity. ▪ Cala Lilly – calcium oxalates ▪ Tiger Lilly – renal toxin Large Animals - Zealalenone – affects PIGS, potent estrogenic metabolite produced by Fusarium o Hyperestrogenism and pseudopregnancy - Salt poisoning - o LESION = perivascular infiltration of eosinophils o Pathogenesis = too much blood sodium causes increased osmolarity and water from the brain diffuses into the vasculature, brain responds by forming hyperosmolar (idiogenic osmoles) to draw water back into the brain – REHYDRATE SLOWLY or will cause water to diffuse into the brain too rapidly ▪ See neurologic signs – head pressing, stargazing, blindness, seizures ▪ Causes hemolysis because water rushes into RBCs and they lyse - COPPER - o Toxicity – common in SHEEP (pigs very resistant to high copper) 3 of 124 ▪ Cattle and horse feed contain too much copper for sheep – most common exposure. ▪ Hemolytic anemia in sheep – liver levels build up until suddenly released causing massive hemolysis and resulting in icterus – will see methemoglobinemia, hemoglobinemia, hemoglobinuria o Deficiency = see in SHEEP – enzootic ataxia, swayback ▪ Primary (low copper intake), secondary (high molybdenum, sulfur, iron, selenium, etc.) ▪ Enzootic ataxia – see in lambs 1-2 months old ▪ Swayback – congenitally or in very young lambs, progressive ascending paralysis - Grass tetany/staggers – o Phalaris (canary grasses – Phalaris, Lolium, Cynodon, Paspalum) - ▪ Stiff-legged gait, hyperexcitability, nystagmus, head tremors, fall and flail wildly ▪ Remove them from the pasture and they should get better o HYPOMAGNESEMIA - ▪ Magnesium important for nervous system function and enzyme reactions ▪ Occur in lactating animals in early spring on lush pastures that are well-fertilized with nitrogen and potassium, high levels of these inhibit magnesium absorption from the GI tract ▪ Restlessness, staggers, over-alert appearance, excitable, fall down with convulsions and die - Black walnut = LAMINITIS in horses - GI TOXINS o Slaframine = moldy red clover ▪ HYPERSALIVATION ▪ slobbers o Oak leaves and acorns - ▪ Hemorrhagic diarrhea, abdominal pain, tenesmus, colic, death ▪ Cattle = renal damage, NOT in horses o Cantharidin = aka blister beetle toxicity ▪ COLICKING in horses, cardiovascular shock, endotoxic shock, renal failure, vesicles in mouth or tongue – watery diarrhea, neuro signs if live long enough Renal tubular damage (may see hematuria), cardiac arryhthmias Abrupt onset of colic, fever, hypersalivation, frequent urination, hematuria o Claviceps purpura = parasitic fungus – ERGOTISM ▪ Found on rye, oats, wheat, and Kentucky bluegrass ▪ Alkaloids causes vascular constriction, thrombosis, gangrene, vomiting, colic, diarrhea, constipation ▪ Find ergot in the grain! - NEUROTOXINS o Blue green algae = Anabaena, Microcystis, Aphanizomenon ▪ Toxin absorbed through mucous membranes, causes post-synaptic depolarizing block ▪ Dead animals next to a pond – i.e. birds and cattle 4 of 124 ▪ Miosis, ptyalism, bradycardia, diarrhea, ataxia, convulsions, death – can die within minutes (as little as 1.5L can kill a cow) ▪ Two kinds: Nicotinic agonists – mimics the mechanism of acetylcholine Acetylcholinesterase inhibitor - o Nightshade = atropine like alkaloid—> causing parasympatholytic ▪ CNS signs – dilated pupils, progressive paralysis, depression txt: physostigmine o Water hemlock – LEAVES very toxic ▪ Grand mal seizures, salivation, tachypnea, birth defects similar to lupine, death o Perennial ryegrass - ▪ Ataxia and tremors as result of activating GABA receptors when infected with an endophytic fungus o Lead poisoning = contaminated petroleum products (i.e. used motor oil) ▪ Acute blindness, dullness, down and unable to rise, vocalizing, unaware of presence ▪ Sample of rumen contents has oily sheen ▪ Treat with Calcium EDTA to chelate – use calcium to help prevent hypocalcemia, do not use sodium EDTA because sodium will bind up calcium and cause hypocalcemia o Sorghum - ▪ Lesion = myelomalacia of lower spinal cord – pelvic limb incoordination, urine dribbling – DEATH o Yellow star thistle = Centaurea solstitialis ▪ Lesion = nicropallidal encephalomalacia – loss of globus pallidus and substantia nigra ▪ Loss of prehension (dystonia of lip muscles and tongue), tremoring, dysphagia, unable to prehend feed – GRAVE prognosis, euthanasia recommended because die of dehydration or starvation - REPRODUCTIVE TOXINS o False hellbore = Veratrum californicum ▪ Teratogen called cyclopamine – cyclopia, anophthalmos, cleft palate, metacarpal hypoplasia Day 14 of gestation = craniofacial deformities Day 30 of gestation = limb and bone shortening in metacarpal/metatarsal joints o Locoweeds (Astragalus, Oxytropis, Swainsona) = abortions, weak lambs, bent legs ▪ Inhibit alpha-mannosidases – widespread neurovisceral cytoplasmic vacuolation – and abortion and neuro system abnormalities (i.e. ataxia) ▪ Grow in WEST with other forages are scarce – see in dry condition in Rocky Mountains 5 of 124 o Fescue = Neotyphodium coenophialum (ergopeptine alkaloids – dopamine agonists) ▪ Prolactin suppression – inhibit lactation, thickened placenta, dystocia, agalactia, prolonged gestation, weak or stillborn foals = REPRO FAILURE IN MARES Reproductive inefficiency, does not cause congenital defects ▪ Clinical signs = lameness, sloughing of rear hooves, decreased weight gain, fat necrosis o Lupine = “crooked calf disease” ▪ Arthrogryposis, malpositioning in the uterus, cleft palate o Ponderosa pine needles - ▪ Abortion in LAST trimester, retained placenta - COAGULOPATHY o Bracken fern = bone marrow suppression (low neutrophils and lymphocytes) ▪ Toxic glycoside (ptaquiloside) and thiaminase ▪ Enzootic hematuria – hemorrhagic cystitis that progresses to neoplastic changes in the bladder ▪ Can cause polioencephalomalacia due to thiaminase – more so in HORSES than other animals o CYANIDE = choke cherry (arrow grass, Sudan and Johnson grasses, Sorghum) ▪ Bright red mucous membranes – cyanide blocks cellular respiration and oxidative transport – hemoglobin unable to release oxygen (venous blood stays oxygenated) ▪ Bright red blood, bitter almond smell to GI tract on necropsy ▪ Treatment = sodium thiosulfate, sodium nitrate, methylene blue (NOT supplemental oxygen) o Carbon monoxide - ▪ Cherry red mucous membranes – differentiate from cyanide by lack of almond smell o Nitrates - ▪ BROWN blood o Moldy sweet clover = vitamin K antagonist = dicumarol (Warfarin like) ▪ Necessary for production of factors II, VII, IX, and X – causes hemorrhage, NOT hemolysis ▪ Prothrombin time (PT) – to diagnose because factor VII depleted first and is part of extrinsic o Anthrax - ▪ Common in horses and cows – sudden death, colic, fever, SQ edema – dead horses do not show signs of rigor mortis with unclotted blood exuding from their orifices ▪ DO NOT NECROSPY THE ANIMAL!! Could release spores into environment. Notify the authorities! ▪ Diagnosis = obtain vitreous humor (or blood from an ear scrape) ▪ ZOONOTIC = human forms are intestinal, pulmonary, cutaneous - CARDIAC TOXINS = 6 of 124 o milkweed, gossypol (in cottonseeds), oleander, rhododendron, foxglove, white snakeroot o All of these can cause acute death or arrhythmias o Ionophores = i.e. monensin (also lasalocid, salmonycin) – toxic to HORSES ▪ Coccidiostat used in cattle – horses very susceptible ▪ Myocardial necrosis and dilated cardiomyopathy – heart murmur, respiratory distress, staggering, profuse sweating, hemoglobinuria – look at fractional shortening with ECHO to determine prognosis ▪ Empty GI tract by using mineral oil, activated charcoal, fluid therapy - PULMONARY TOXINS o Perilla mint = type I pneumocytes and bronchiolar epithelial cells ▪ Dyspnea, frothing at the mouth – wet, emphysematous lungs on necropsy ▪ High mortality because get permanent fibrosis of the lungs o Moldy sweet potatoes = Fusarium solani ▪ Produces 4-ipomeanol (4-IP) – atypical interstitial pneumonia ▪ Grunting, frothing at mouth, deep cough, respiratory distress, death after 2-5 days ▪ Lungs wet, firm and fail to collapse – same lesions as seen with 3-MI o Brassica plants = rape, kale, turnips = FOG FEVER (acute bovine pulmonary edema and emphysema, grunts) ▪ Contain lots of tryptophan which is converted to 3-methyl-indole (3-MI) – leads to atypical interstitial pneumonia and emphysema and cyanosis ▪ Seen in cattle on lush forage - frothy nasal discharge, SQ emphysema, loud cough, open mouth breathing, crackles and wheezes - HEPATIC TOXINS o Pyrrolizidine alkaloids = fiddleneck (Amsinkia intermedia), common groundsel, ragwort, Senecio ▪ Inhibit mitosis of hepatocytes so can’t multiple – acute liver failure, hepatic encephalopathy, icterus ▪ Diagnostic = megalocytosis, periportal fibrosis, bile duct hyperplasia Presents similar to Theiler’s disease – in horses – use histopath to differentiate ▪ May also see secondary photosensitization = sunburned white areas on skin Normal chlorophyll breakdown products (phylloerythrin) are usually cleared by the liver, with liver damage this accumulates in the skin and results in UV damage Primary photosensitization = St. John’s Wort, Erodium, Brassica, Hypericum o Contain hypericin – causes large areas of skin sloughing, mainly unpigmented areas Photosensitization due to liver disease – usually chlorophyll in diet is converted to phylloerythrin and excreted by the liver – with hepatic disease it is deposited in skin – UV reacts with it and causes dermal damage ! lesions on weight areas o Aflatoxin = mycotoxin (from Aspergillus) ▪ Similar lesions to PAs - but pathologists thing megalocytes is pathogenic for PAs Subacute hepatic necrosis and fibrosis ▪ Primarily found in moldy grains 7 of 124 Clinical Pathology and Hematology - Miscellaneous facts - o Lactate – can measure to assess perfusion – reflection of anaerobic metabolism (normal