Exam 2: Hemoglobinuria, hematuria, and neurotoxins Flashcards
Know the mechanism of action of plant induced hemoglobinuria
plant sulfides (traditionally n-dipropyl disulfide, but a wide variety of oxidative compounds) inhibit glucose-6-phosphate dehydrogenase.. oxidant injury to hemoglobin and RBC to form heinz bodies
Why are cats more susceptible to Heinz body formation?
Oxidation of reactive sulfhydryl (S-H) groups creates disulfide bonds that change the conformation of the hemoglobin protein chains, resulting in precipitation and Heinz body formation
Cats have low glucuronyl transferase = Slow metabolism of compounds with -OH, -COOH, -NH2, -HN, and -SH
Cats have 4x S-H groups in Hb than humans
Onion poisoning – toxin, MOA, clinical signs, treatment
Toxin: organosulfur compounds including n-propyl disulphide
Clinical Signs:
Hemoglobinuria
Weakness, ataxia
Anemia/Pale membranes
Tachycardia
Onion odor
Treatment:
Remove the onion source
Blood transfusions in severely anemic patients
Avoid stressing the animal
Brassica induced hemoglobinuria – toxin, MOA, major members of the Brassica family.
Plants of the Brassica spp. including turnips, kale, rape, cabbage, and brussel sprouts
have been associated with hemolytic anemia in cattle. Hemolytic anemia occurs in cattle
due to the presence of the compound S-methyl-L -cysteine-sulfoxide (SMCO), a sulfur
containing amino acid unique to the family Brassicaceae. –> also leading to heinz body anemia and hemoglobinurea but has many syndromes
Brassica syndromes – list 5 associated syndromes and treatments, if any.
SMCO
Disulfides
Hemoglobinurea
Glucosinolates
Isothiocyanates/thiocyanates
Goitrogenic
Tryptophan in turnip tops
Rumen converts to 3-methyl indole
Pulmonary emphysema / edema
Turnips- high sulfur content,
Thiamine deficiency
copper deficiency
Polioencephalomalacia/Blindness
Hepatotoxicity
Describe how the Descurainia spp. Tansy mustard and Flixweed induce thyroid hyperplasia. Toxin, MOA, treatment/prevention.
The glucosinolate-derived thiocyanates inhibit iodine uptake and can reduce T3 and T4 production. The reduced thyroid hormone levels result in increased thyroid stimulating hormone from the pituitary gland and ultimately thyroid hypertrophy.
In addition to hepatogenous photosensitization Flixweed (Descurainia) is a potential goitrogen
Flixweed can cause significant reproductive failure in goats and should not be fed to pregnant goats.
Remove flixweed from diet and supplement Iodine
Red Maple poisoning – which maples, other trees? Animals effected, Clinical signs/ postmortem damage
red maple (acer rubrum) and hybrids (silver, and sugar) and gallic acid and pyrogallol in pistacia trees
Clinical Signs:
Heinz body anemia/Brown/red urine
Methemoglobinemia
Weakness, lethargy
Icterus, elevated liver enzymes
Postmortem:
Splenomegaly
Enlarged liver with pale centrilobular areas
Brownish/Black kidney
Moldy Sweet clover poisoning – What is toxic principle, How is it created? MOA? Clinical signs? Treatment?
Yellow sweet clover is not poisonous, but fungi can convert coumarin to Dicoumarol. Dicoumarol interferes with the production of vitamin K and therefore affects vitamin K dependent coagulation factors VII, IX, X and prothrombin.
Clinical Signs:
Weakness, depression
Hematomas
Hematuria
Hemarthrosis
Hyphema
Abortion
“No blood clotting”
Prothrombin time > 40sec.
(normal 9-12 sec.)
Whole blood transfusions
Vitamin K1
0.5-2.5mg/kg bw IM
Treatment for 1-2 weeks
Vitamin K3 less effective!
Risk of vitamin K renal toxicosis in horses
What are the 3 primary toxins associated with locoweed (Astragalas and oxytropis)?
Swainsonine
A lysosomal storage disease
Miserotoxins
Nitrotoxins – ‘Cracker heels’
Selenium accumulators
Lameness, hair loss
Photosensitization – Astragalus cicer
Locoweeds are similar in nutrient value to alfalfa
How is swainsonine produced and what is its mechanism of action?
Endophyte Embellisia spp. produces swainsonine
Not found in all Astragalus and Oxytropis species
Passed through milk
Affects all animals
Highest in flowers/seeds
0.75-1 lb/day for 75-85 days
Inhibits alpha mannosidase and golgi mannosidase II
Oligosaccharides accumulate
Lysosomal storage disease
Alters hormone/cytokine/ receptor function
What are the clinical syndromes associated with swainsonine poisoning in locoweed?
CNS signs –”locoism”
Horses common
Depression
Incoordination
Staggering gait
Unpredictable behavior
Prognosis guarded
Reproductive failure
Abortions
Congenital defects (crooked legs)
Hydrops
Reduced fertility
Poor growth rates
(can mimic Bovine Virus Diarrhea)
Congestive heart failure
Lowered immune response
How might swainsonine poisoning be diagnosed?
Availability of plant
Serum Swainsonine (t1/2 -16-20 hrs)
↓ α-mannosidase activity (6 days)
Elevated AP, AST, LDH
Reduced T3/T4, serum protein
Cytoplasmic vacuoles in lymphocytes
Sage poisoning – Clinical signs, toxins
Sage is predominant in the horses diet
Breath and feces smell of sage
Variable neurologic signs
Depressed, walk in circles, stumble
‘looks like locoweed poisoning’
Nonspecific degenerative encephalopathy
Recover when taken off sage
Various Monoterpene toxins (horses)
Similar to thujone, toxin in absinthe
Sesquiterpene lactones (other species)
What are 2 common plants associated with chewing disease? Clinical signs?
russian knapweed, yellow star thistle
Hypertonicity of facial and tongue muscles
Cannot prehend or chew normally
‘Chewing disease’
Inhalation Pneumonia
Circling, head tossing
Dehydration, starvation lead to death
What areas of the brain are necrotic in the Nigropallidalencephalomalacia that are the classic lesions in chewing disease?
Bilaterally symmetrical foci of liquefactive necrosis in the globus pallidus and substantia nigra
