Blakley #2 Flashcards
what is metaldehyde
a molluscide used to control snails and slugs
absorption of metaldehyde
well absorbed in intestine; can become addicting to dogs
metabolism of metaldehyde
rapidly metabolized to acetaldehyde
distribution and excretion of metaldehyde
readily crosses BBB, metaldehyde is responsible for toxicity, acetaldehyde causes vomiting/tremors and is excreted in urine
mechanism of action of metaldehyde
reduces GABA and serotonin levels in brain causing CNS excitation (occasionally depression); depression of medullary respiratory center leads to death
minor mechanisms of metaldehyde
gastroenteritis (chemical irritation), brain damage, mild liver damage
clinical manifestations of excitatory syndrome of metaldehyde toxicity
salivation, tremors, ataxia, continuous convulsions, opisthotonus, nystagmus (cats), elevated BT
clinical manifestations of depressive syndrome of metaldehyde toxicity
emesis, depression, incoordincation, increased RR and HR, cyanosis and coma
PM findings of metaldehyde toxicity
non-specific lesions; congestion and mild hemorrhage of liver, kidney and GIT; stomach smells like apple cider, large amount of content
what does the stomach contents of metaldehyde toxicity smell like
apple cider from acetaldehyde
diagnosis of metaldehyde toxicity
sudden onset of neuro signs, large quantities of pleasant smelling stomach contents, analysis of stomach contents
treatment of metaldehyde toxicity
sedation, anesthesia, emetics, fluids (shock/acidosis) +/- activated charcoal (crisis usually over in 24 hours due to rapid elimination)
species susceptibility with strychnine toxicity
all mammals are highly susceptible (dogs are the most); secondary poisoning/relay toxicity is common
absorption of strychnine
rapidly absorbed; clinical manifestations within 15 minutes to 1 hour
distribution of strychnine
can be detected in liver, kidney, brain, blood or stomach contents (stomach contents are best)
metabolism and excretion of strychnine
metabolized rapidly by liver with half life of 10 days; excreted in urine and saliva
mechanism of action of strychnine
strychnine competitively antagonizes glycine resulting in loss of inhibitory processes and neurological excitation (glycine in the predominant inhibitory neurotransmitter at level of spinal cord and medulla); interferes with post-synaptic inhibitory control at level of spinal cord; also alters K ion gates postsynaptically leading to motor neuron excitability
why does strychnine not interfere with post-synaptic inhibitory control in the brain
because it is regulated by GABA, not glycine
clinical manifestations of strychnine toxicity
sudden onset, apprehension, nervousness, tenesmus, rigid muscle (especially face), tetanic seizures begin in 15 minutes-2hours (extensor rigidity of all 4 limbs), as more strychnine is absorbed relaxation periods between seizures becomes shorter, seizures can be triggered by external stimuli, apnea (anoxia, coma and death within 1-2 hours)
PM findings of strychnine toxicity
no specific lesions because it is a neuro/biochem disturbance; agonal congestion and hemorrhage due to nature of death
diagnosis of strychnine toxicity
sudden death in normal healthy dog; analysis of stomach contents, vomitus or liver
treatment of strychnine toxicity
emergency treatment, apomorphine (emetic; prior to seizures), gastric lavage with activated charcoal or tannic acid (bind/precipitate strychnine), potassium permanganate, sedation, muscle relaxants
most important treatment for strychnine toxicity
sedation
which are the coumarin derivative anticoagulant rodenticides
warfarin, brodifacoum, difencoum
which are the indane dione derivative anticoagulant rodenticides
diphacinone, chlorophacinone, pindone, valone, bromadiolone
toxicity of anticoagulant rodenticides
first generations require repeated exposure for 1-2 weeks; second generation can have problems with a single dose
absorption of anticoagulant rodenticides
well absorbed
distribution of anticoagulant rodenticides
highly protein bound
metabolism and excretion of anticoagulant rodenticides
excreted in urine; warfarin has a half-life of 44 hours; second generations are fat soluble and have longer half lives
mechanism of action of anticoagulant rodenticides
complete inhibition of vitamin K epoxide reductase (reduced vitamin K is required for activation of factors 2, 7, 9 and 10)
when does bleeding occur with anticoagulant rodenticide toxicity
clotting times will be prolonged 3 days after exposure; bleeding by days 4-5 or later
factors altering toxicity of anticoagulant rodenticides
high fat diet, prolonged oral antibiotics (sulfonamides), protein binding drugs, liver disease, prolonged GIT disturbance
clinical manifestations of anticoagulant rodenticide toxicity
severe hemorrhage, sudden onset, dyspnea, anemia, melena, rapid irregular HR, hematoms, abortion, proprioceptive deficits and tender abdomen with 2nd generation products
diagnosis of anticoagulant rodenticide toxicity
elevated coagulation time, elevated PT/PTT, normal platelet count and WBC count, reduced PCV, thoracocentesis, chemical analysis of blood, liver and urine
PM findings of anticoagulant rodenticide toxicity
generalized hemorrhage, mild hepatic necrosis associated with hypoxia from lack of perfusion
treatment of anticoagulant rodenticide toxicity
avoid trauma, blood transfusion,vitamin K1 (oral, takes 12 hours), cholestryamine (bile sequestrant to reduce enterohepatic circulation)
how long does vitamin K1 need to be given to 2nd generation anticoagulant rodenticide toxicity animals
4-6 weeks; if you shorted treatment they will relapse by 8-9 days later so want to check at 4 (warfarin needs only 1 weeks)
why don’t you treat anticoagulant toxicity with vitamin K3
because it requires metabolic activation – epoxide reductase is inhibited by the anticoagulant
what are the toxicokinetics of alpha-naphthyl thiourea (ANTU)
rapid absorption, metabolism, and excretion; symptoms within an hour
mechanism of action of ANTU
increases permeability of pulmonary capillaries (transudates in airway); cause of death is anoxia from decreased lung perfusion
clinical manifestations of ANTU
vomiting, salivation, dyspnea, frothing/coughing, cyanosis, increased HR that sounds muffled, dog sitting position to increase lung volume, schock
PM findings of ANTU
massive pulmonary edema; hydrothorax and froth, agonal hemorrhage and congestion
diagnosis of ANTU toxicity
history, clinical and pathological changes; chemical analysis needs to be done within 24 hours of death
treatment of ANTU toxicity
diuretics, steroids and atropine (all too slow to be clinically significant)
what is fluoroacetate
one of the most potent toxic rodenticides, water soluble, colorless, odorless powder
toxicokinetics of fluoroacetate
rapidly absorbed, metabolic activation is required so there is about a 1 hour delay before clinical signs
mechanism of action of fluroacetate
replaces the acetyl coenzyme A in the Kreb’s cycle; (converted to fluorocitrate, the aconitase enzyme that would normally convert citric acid to isocitric acid is inhibited by fluorocitrate) – cellular respiration and energy production stop due to blocked kreb’s cycle
clinical manifestations of fluoroacetate poisoning (early stages)
restlessness, hyperirritability, frenzy, barking
clinical manifestations of fluoroacetate poisoning (late stages)
vomiting, diarrhea, tenesmus, urination, defecation, dyspnea, intermittent tonic-clonic convulsions, periods of running (dogs), cardiac arrythmia and fibrillation, vocalization (cat), elevated BT
PM of fluoroacetate poisoning
no pathognomonic lesion; agonal hemorrhage and congestion
diagnosis of fluoroacetate poisoning
death within 2-12 hours (respiratory failure, cardiac arrythmia and fibrillation), history, clinical and PM
why is analysis of fluoroacetate difficult
because it is no longer present as fluoroacetate
treatment of fluoroacetate
calcium ketoglutarate can be beneficial to correct the Ca imbalance and ketoglutarate provides and essential energy substrate after the metabolic block
absorption of zinc phosphide
reacts with stomach acids to form phosphine gas – instantaneous, gas is readily absorbed
excretion and metabolism of zinc phosphide
both parent compound and phosphine gas are eliminated readily
mechanism of action of zinc phosphide
irritant and inhibits cytochrome C oxidase
clinical manifestations of zinc phosphide
irritation can cause vomiting; 4-5 hours later – depression, tremors, hyperesthesia, seizures, running has been observed, salivation and dyspnea. (colic and bloat in livestock)
PM of zinc phosphide toxicity
congested lungs with interlobular edema, gastritis, irritation, tubular degeneration and necrosis of kidney, fatty degeneration of liver, stomach contents may have acetylene or garlic odor
what do the stomach contents smell like with zinc phosphide
garlic odor or acetylene
diagnosis of zinc phosphide toxicity
analyze stomach contents for zinc
treatment of zinc phosphide toxicity
fluids and bicarb to control shock and acidosis; atropine to reduce pulmonary secretions; poor prognosis
what is cholecalciferol
a vitamin D product that tends to have toxic irreversible damage (syndrome can be produced by ingestion of rodent baits, vitamin D supplements or excessive levels of vitamin D in feed)
toxicokinetics of cholecalciferol
rapid absorption, symptoms within 24 hours, metabolized in liver and excreted in kidney
mechanism of action of cholecalciferol
increased absorption of Ca from GIT and enhanced Ca mobilization from bone – hypercalcemia causes conduction problems and metastatic calcification of soft tissues
clinical manifestations of cholecalciferol
vomiting, anorexia, diarrhea, tremors, hypoesthesia, depression and lethargy
PM of cholecalciferol
with sufficient dose death occurs in 24 hours; calcification in kidney, hemorrhagic gastroenteritis, mineralization, degeneration and necrosis in other organ systems
normal ionophore mechanism of action
increases intracellular Na and decreasing intracellular K – alters electrolyte balance of host, bacteria and protozoa (increases propionic/acetic acid ratio thus improving energy utilization)
ionophore mechanism of toxicity
K transport is altered in the mitochondria leading to reduced ATP hydrolysis and energy production; possibly also cause increase in Ca intracellularly (heart is very susceptible); as intracellular K decreases, cytotoxicity increases
toxicokinetics of ionophores
limited absorption, rapid metabolism, short withdrawal times
species susceptibility differences in ionophore susceptibility
horses are the most susceptible, chickens are the least
predisposing factors to ionophore toxicity
vitamin E/Se deficiency, T-2 toxin exposure, drug interactions
clinical manifestations of ionophore toxicity (horses)
leg weakness progressing to paralysis, sore muscles, staggering, ataxia, reluctant to move, huge increased HR, congested MM, hemoconcentration, hypovolemia, shock, arrythmia, dyspnea, anorexia, sweating, ventral pitting edema (later)
PM of acute sudden death ionophore toxicity
no lesions
PM of delayed death ionophore toxicity
myopathy and CHF are evident with hydrothorax, ascites, pulmonary edema
diagnosis of ionophore toxicity
need to run tests on day 1; myoglobinuria, creatinine phosphokinase, LDH2 (reflects RBC membrane damage), ECG (T wave depression and S-T segment depression), hemoconcentration, tryponin (cardiac specific)
what may chronic monensin toxicity show
edema on the feet
treatment of ionophore toxicity
muscle damage is permanent; fluids and steroids for shock but be cautious (if kidney damage), mineral oil, diuretics (caution), vitamin E/Se
what species is most affected by salt poisoning
swine
what is required for salt poisoning
water deprivation and an imbalance of Na and water
when do animals have increased water requirements
lactation, renal disease, high salt intake, high protein intake, high environmental temperature, exercise
causes of water deprivation
medicated water, frozen water supplies, faulty water system, overcrowding, new surroundings, neglect, electrified water system
mechanism of action of salt poisoning
restricted water intake causes the blood and brain Na levels to rise; inhibition of anaerobic glycolysis and energy processes necessary for brain; the levels of ATP necessary to remove Na from brain don’t work; if water is restored Na concentration in blood rapidly declines; thus to maintain osmotic balance water moves into the brain (AA in brain also contribute to its high osmolarity)
clinical manifestations of salt poisoning
intermittent tonic-clonic seizures, depression, anorexia, blind, deaf, aimless wandering, circling, opisthotonus, head pressing
clinical manifestations of salt poisoning in cattle
diarrhea and anorexia; neuro signs not common
PM of salt poisoning
few gross lesions; mild gastric inflammation and ulcers
Histology of salt poisoning
eosinophilic meningoencephalitis, cerebral edema and necrosis, macrophage infiltration of cortex, endothelial proliferation of white matter
diagnosis of salt poisoning
elevated sodium levels in serum, CSF, brain
treatment of salt poisoning
controlled water intake after deprived period could help; no successful treatment – just take to butcher
what do many fertilizers contain
urea (46-0-0) and ammonium (34-0-0)
how do you differentiate whether fertilizer contained urea or nitrate based on the animal
urea will be hydrolyzed in the gut causing increased rumen pH and normal colored blood; nitrate fertilizer causes chocolate brown blood and normal pH
species susceptibility of urea poisoning
only ruminants are susceptible; horses to a certain extent; (all species susceptible to ammonium ion)
how is urea utilized in the rumen
it is hydrolyzed by rumen microflora to form ammonia and carbon dioxide by the urease enzyme (not regulated); ammonia is incorporated by rumen microflora into protein; excess ammonia is transported to liver where it is converted back to urea and excreted in urine (can also be recycled into AA)
when does urea toxicity result
when the capacity of the recycling system for ammonia is exceeded – high levels of ammonia result in toxicity
what are the optimal conditions for urea hydrolysis
pH of 7.7-8.0 and temperature of 49C
predisposing factors to urea toxicity
no previous urea exposure (naive microflora), fasting, starvation, dehydration (can’t excrete in urine), hepatic insufficiency, high roughage diet (more optimal pH), elevated BT, stress, disease ((Young are less susceptible))
biochemical changes in urea toxicity
excess ammonia enters blood causing and increased pH and inhibition of the Kreb’s cycle –> compensatory glycolysis to elevated blood glucose and lactic acid –> drop in pH; inhibition of energy processes cause increase K release from cells with cell membrane damage and thus cardiotoxicity; ammonia also has strong irritant effect on lungs
clinical manifestations of urea toxicity
onset can be within 10 minutes; restlessness, belligerant periods, head pressing, hyperesthesia, tremors, twitching, spasms, eyelids, tonic seizures, opisthotonus, saw-horse stance, rumen stasis, bloat, groaning, grinding teeth, no diarrhea, frothy salivation (lose urea through saliva), incoordination, recumbency of front end, dyspnea from pulmonary edema, jugular pulse, hyperthermia
what are the most notable signs of urea toxicity
GIT signs; rumen stasis, bloat, groaning, grinding teeth, no diarrhea, frothy salivation (lose urea through saliva)
PM of urea toxicity
rumen pH greater than 7.5 (do ASAP because ammonia evaporates), pulmonary edema, ammonia odor, catarrhal gastroenteritis, petechial hemorrhage
diagnosis of urea toxicity
measurement of blood and rumen pH; also ammonia levels
treatment of urea toxicity
administer vinegar and cold water (make rumen environment less ideal for urease enzyme)
factors related to plant growth that increase the likelihood of plant poisoning
age of plant, growth conditions, portion of plan, plant injury, post harvest storage, plant species, soil condition, fall sprouting
what toxic compounds are present in oak
gallotannins and polyhydroxyphenolic compounds
where are toxic compounds present in oak
leaves and acorns
mechanism of action of oak toxicity
tannins act as astringents to destroy epithelial cells of GIT and renal
clinical manifestations of oak toxicity
GIT signs first then renal insufficiency; anorexia, dullness, colic, rumen stasis, dehydration, emaciation, constipation then hemorrhagic diarrhea, hematuria, polyuria, ascites and hydrothorax, icterus
PM of oak toxicity
GIT ulcers, enteritis, edema, ascites, tubular nephrosis and necrosis, acorns in rumen, hyaline membrane
clinical pathology of oak toxicity
elevated BUN and creatinine, elevated liver enzymes, altered electrolytes, USG low, hematuria, proteinuria
treatment of oak toxicity
add CaOH to grain ration to precipitate gallotannins in gut and prevent absorption; reduce access, supplemental feed
diagnosis of oak toxicity
GI problems, kidney problems, time of year, history
mechanism of action of red maple toxicity (acer rubrum)
component of leaves causes oxidative damage characterized by intravascular hemolysis and methemoglobinemia
clinical manifestations of red maple toxicity
weakness, increased RR and HR, pale, hemoglobinuria, hemoglobinemia, jaundice, anemia, methemoglobinemia, heinz bodies
treatment of red maple toxicity
non are very effective, especially if methemoglobinemia is present; blood transfusion, fluids, peritoneal dialysis
susceptibility of species to nitrate/nitrite poisoning
primarily a problem in ruminants; monogastrics have a limited ability to convert nitrate to nitrite (unlikely to develop toxicity) but can see with consumption of brines containing nitrite
sources of nitrate
forage crops, nitrate fertilizer, contaminated water, numerous weeds – both feed and water sources will produce additive effects (10x more available in water)
factors influencing nitrate accumulation in plants
high soil nitrate, plant species, part of plant (stalk and leaves are higher), age of plant (immature>mature), drought, light and length of day (nitrate reductase requires light), temperature (frost reduces nitrate metabolism), soil pH, plant disease, herbicide application, aeration of soil, Mo, S and P deficiency (needed for reductase), late season sprouting
mechanisms of action of nitrate/nitrite toxicity
both are toxic but nitrite ion is more toxic; nitrate converted to nitrite in rumen; under normal circumstances nitrite is converted to ammonia or AA
what is the rate limiting step of nitrate/nitrite metabolism
metabolism of nitrite to ammonia/AA
nitrate effects
Cl displacement causing hypochloremia and alkalosis, diuresis (dehydration), GIT irritation, iodine displacement (goitre)
nitrite effects
methemoglobin formation (hemoglobin oxidation), vasodilation, NO2 gas formation causing pneumonitis, vitamin A inactivation
how does death occur with nitrate/nitrite toxicity
tissue anoxia
clinical manifestations of nitrate/nitrite toxicity
nitrate causes gastroenteritis, abdominal pain, diarrhea and salivation; nitrite causes severe manifestations in 4 hours with death in 12-24 as a respiratory distress syndrome (cyanosis, rapid weak HR, dyspnea, muddy chocolate brown MM, urination, incoordination, muscle weakness, abortion, bloat, coma, convulsion, death
PM of nitrate/nitrite toxicity
mild gastroenteritis, chocolate brown discoloration of most tissues, petechial hemorrhage in heart and trachea, poorly clotting blood, and mild pulmonary edema
susceptibility of adult versus fetus to nitrate/nitrite toxicity
fetal hemoglobin is more readily converted to methemoglobin therefore fetus is more susceptible than adult
diagnosis of nitrate/nitrite toxicity
feed analysis, water analysis, methemoglobin levels are best measurement
treatment of nitrate/nitrite toxicity
methylene blue is best (if you overdose though you end up with more methemoglobin), vasoconstrictors, vitamin A supplementation, mineral oil
prevention of nitrate/nitrite toxicity
dilute high nitrate feeds, feed highly fermentable carbohydrate ration
what are hydrocyanic acid or prussic acid poisoning associated with the ingestion of (cyanide poisoning)
ingestion of plants containing cyanogenic glycosides
what is the toxic principle of plants containing cyanogenic glycosides
HCN – small molecule that is well absorbed from resp and GI
sources of cyanide
plants or pits of various fruits; peaches, cherries, almonds, sorghum, sudan grass, cherry leaves, arrow grass, white clover
factors affecting cyanide accumulation
what changes nitrate a little bit, changes CN a lot; wilting, trampling, frost, drought, herbicide, fertilizer, age of plants (younger contain more), declining day length
species susceptibility of cyanide poisoning
ruminants > monogastrics because greater capacity to metabolize cyanogenic glycosides (horses and swine are less susceptible)
metabolism of CN
80% is metabolized in liver by rhodanase enzyme, CN accepts sulfur molecule to form thiocyanate (SCN); 15% of CN can be excreted unmetabolized in lungs or urine
when does CN toxicity occur
when the natural detoxification system (SCN) is exceeded or the source of sulfur is depleted
what smell can be detected in exhaled gases or rumen contents of CN poisoned animals
bitter almond smell
mechanism of action of CN toxicity
high binding affinity for ferric compounds; forms a stable inactive complex with cytochrome oxidase thus stopping cellular respiration leading to acute histotoxic anoxia
clinical manifestations of cyanide toxicity
life threatening manifestations within 15 minutes to an hour, excitement, rapid breathing to dyspnea, muscle twitching, tremors, staggering, terminal anoxic convulsions, opisthotonus, nystagmus, pupil dilation, cyanosis, bloat, blood is bright cherry red
what color is the blood in cyanide toxicity
bright cherry red (highly oxygenated but no oxygen change occurs)
PM of cyanide toxicity
MM are congested and bright red, gastroenteritis, unclotted blood often, endocardial hemorrhage and congestion, bitter almond smell in rumen (with chronic poisoning can observe axonal degeneration and demyelination)
diagnosis of cyanide poisoning
acute toxicity with sudden onset of neuro symptoms and confirmed by measurement of cyanhemoglobin in heparinized blood (analysis needs to be within 4 hours because CN will dissipate); can also look at rumen contents, plant, liver and muscle; field test for CN with color reaction
treatment of cyanide poisoning
sodium thiosulfate IV (thiosulfate reacts with cyanhemoglobin to produce thiocyanate and functional hemoglobin; stress of handling often kills more than helps
goitrogenic syndrome of chronic cyanide poisoning
cyanide is thyrotoxic so observe goitre in lambs
sorghum cystitis of chronic cyanide poisoning
horses consuming sorghum or sudan grass develop a syndrome characterized by neuronal degeneration (neuro and nephro); ataxia (axonal degeneration and demyelination), cystitis, urinary incontinence, pyelonephrities, joint fixation in fetus
livestock oxalate poisoning is caused by
ingestion of plants containing oxalates and produces syndrome with hypocalcemia and renal failure
pet oxalate poisoning is caused by
ingestion of ethylene glycol producing syndrome with metabolic acidosis and renal failure
plants that contain Na or K salts of oxalates
rhubarb leaves, beet leaves, halogeton, greasewood
susceptibility to plant oxalate poisoning
sheep are more susceptible than cattle; pregnant/lactating or hungry animals that eat large quantities are more susceptible
toxicokinetics of plant oxalate poisoning
Na and K oxalate salts are well absorbed; Ca salts are poorly absorbed (can feed CaOH to bind to Na/K oxalates in gut); Na/K salts complex with Ca in blood, rumen wall or capillaries
how does rumen normally handle Na/K oxalate salts
microflora metabolize the two carbon oxalate molecules to form CO2 and bicarb – when this is overwhelmed oxalate salts are absorbed
factors influencing plant oxalate toxicity
dose, rate of ingestion, type of tumen microflora (can adapt), high Ca is protective in feed (so is low pH), cobalt deficiency increases toxicity, water consumption causes increased absorption
mechanism of action of plant oxalate toxicity
hypocalcemia from formation of Ca oxalate; oxalate crystals damage renal epithelium, capillaries and rumen wall
clinical manifestations of plant oxalate toxicity
milk fever 2-6 hours after ingestion (paresis, muscle weakness, twitching, increased HR), osteodystrophia fibrosa (chronic ingestion by horses), nephrosis, urinary calculi, vascular damage, rumen dysfunction
diagnosis of plant oxalate toxicity
low calcium, reduced PCV, elevated BUN
PM of plant oxalate toxicity
ascities, hydrothorax, oxalate crystal striations in kidney, urinary calculi, rumenitis
treatment of plant oxalate toxicity
oral administration of CaOH to precipitate in GIT and calcium borogluconate with caution
prevention of plant oxalate toxicity
dietary supplementation with Ca, don’t feed to pregnant/lactating
ethylene glycol mechanism of action
first 2-4 hours has a narcotic effect, next 24 hours ethylene glycol is metabolized to aldehydes and acids (ultimately oxalic acid)
clinical manifestations of ethylene glycol toxicity
alcohol intoxication in first 4 hours (depression, vomiting, ataxia, incoordination, diuresis); metabolic acidosis leads to increased HR and RR; by 48 hours, uremic state due to renal damage, elevated BUN and AG, reduced blood pH, proteinuria, hematuria, hyperglycemia
when is it crucial to diagnose ethylene glycol toxicity
prior to irreversible kidney damage; do a blood gas
PM of ethylene glycol toxicity
gastritis, pale swollen kidney with oxalate striatins, mild pulmonary edema
diagnosis of ethylene glycol
blood gas, kits to detect ethylene glycol in blood
treatment of ethylene glycol
4-methylprazol in dogs only (inhibits alcohol dehydrogenase and prevents oxalate formation); butylene glycol for cats; fluids and bicarb for acidosis and shock, activated charcoal very early on
which fungus produces aflatoxin
aspergillus
which plant is aflatoxin (mycotoxin) associated with
peanuts
mechanism of action of aflatoxin
inhibits protein synthesis by affecting both mRNA synthesis and DNA synthesis
target organ of aflatoxin
liver
clinical manifestations of acute aflatoxin toxicity
depression, poor production, anorexia, rumen stasis, ataxia, icterus and hematomas
clinical manifestations of chronic aflatoxin toxicity
reduce feed efficiency, weight gain and milk production, anorexia, icterus, anemia, ascites, large abdomen
PM of acute aflatoxin toxicity
centrilobular hepatic necrosis, bile duct proliferation and fibrosis, hemorrhage, ascites
clinical pathology of aflatoxin toxicity
mild anemia, elevated liver enzymes, increased bilirubin, increased PT, decreased BUN, reduced CMI (decreased WBC)
diagnosis of aflatoxin toxicity
chemical analysis of feed, possibly tissues (bile, liver kidney)
residue concerns with aflatoxin toxicity
rapidly cleared in 3-4 days; secreted in milk at relevant levels; carcinogen
treatment of aflatoxin toxicity
remove from feed; possibly vitamin E/Se
what fungus produces zearalenone mycotoxin
fusarium
what crop is zearalenone associated with
corn – also present in many types of grain
zearalenone toxicokinetics
well absorbed, rapid metabolism, enterohepatic recycling prolongs retention, secreted in milk
mechanism of action of zearalenone toxicity
binds receptors for estradiol causing estrogenic effects; inhibits secretion and release of FSH leading to inhibition of follicle maturation
clinical manifestations of zearalenone toxicity
older cattle and swine are more resistant; infertility, anestrus, stillbirth, vulvovaginitis(swine), vaginal/rectal prolapse (cattle),pseudopregnancy, early embryonic death, repeat breeding
diagnosis of zearalenone
based on clinical signs of estrogenic effects; typically a herd problem
treatment of zearalenone
remove from contaminated feed; repair prolapses, prostaglandin F2 alpha will reduce the CL
residue concerns with zearalenone toxicity
not a concern
fungus that produces trichothecene mycotoxin
fusarium
3 most common metabolites of trichothecene mycotoxins in canada
T-2 toxin (5x more toxic than DON), DAS, and vomitoxin/DON (least toxic)
species susceptibility to trichothecene mycotoxins
pigs and horses are more susceptible than cattle
mechanism of action of trichothecene mycotoxins
potent inhibitors of protein synthesis, inhibit DNA/RNA synthesis, directly cytotoxic (destroy lymphocytes), immunosuppressive, irritation, vomitoxin crosses BBB and activates emetic centers
clinical manifestations of trichothecene mycotoxin toxicity
feed refusal is presenting complaint; dermal necrosis, gastroenteritis, hemorrhage, leukopenia, embryotoxic, abortion, weakness, ataxia, depression
metabolism and excretion of trichothecene mycotoxins
rapid metabolism and excretion with residues not being a major concern
diagnosis of trichothecene mycotoxins
analysis of feed
treatment of trichothecene mycotoxin toxicity
remove from feed and symptomatic; antibiotics for secondary infections, treat ulcers, fluids
fungus that ergot is produced by
claviceps;
what plants are trichothecene mycotoxins in
brome grass, sedge grass, rye, wheat, barley, oats, triticale
what is the most sensitive indicator of ergot exposure
agalactia associated with reduced prolactin production and mammary gland development (persists for entire lactation)
what syndrome is associated with higher levels of ergot contamination
convulsive
mechanism of action of ergot toxicity
induces contraction of smooth muscles;vasoconstriction of arteries; alpha-adrengergic blocking effect
toxicokinetics of ergot
absorption orally is slow and incomplete, rapid metabolism, excreted in bile (reaches steady state with chronic exposure)
convulsive syndrome of ergot toxicity manifestation
CNS stimulation, hyperexcitability, tremors, hypermetria, ataxia, belligerance, convulsions
gangrenous syndrome of ergot toxicity manifestations
follows prolonged exposure at lower levels; unthrifty appearance due to vasoconstriction of rumen wall causing decreased VFA absorption, lameness in hindlimbs, elevated HR and RR, reduced milk production
effect of ergot toxicity late in gestation
inhibitory effects on prolactin leading to agalactia and neonatal starvation; horses are most susceptible
diagnosis of ergot
clinical signs and feed analysis
treatment of ergot toxicity
remove from contaminated feed
fungus associated with ochratoxin
aspergillus, penicllium
primary target organ of ochratoxin
kidney
mechanism of action of ochratoxin
binds to proteins and reduces synthesis; alters carbohydrate metabolism; inhibits carboxypeptidase; reduces t+mRNA synthesis; increases free radical production
clinical manifestations of ochratoxin
uremic syndrom, anorexia, vomiting, diarrhea, dehydration, depression, PU/PD, immunosuppression, teratogenicity
clinical pathology of ochratoxin
elevate PCV, BUN and serum creatinine, proteinuria, glucosuria, casts, elevated liver enzymes
PM of ochratoxin
nephrosis, pale swollen kidneys, interstitial fibrosis/necrosis, tubular swelling and atrophy, thickened basement membranes, necrosis of liver, gastritis with possible ulcers
fungus that produces dicoumarol
penicillium
what plant is dicoumarol associated with
moldy sweet clover
mechanism of action of dicoumarol
competes for the same receptor as vitamin K thus inhibiting synthesis of vitamin K dependent coagulation factors (prothrombin, 7, 9, 10)
susceptibility to dicoumarol
influenced by protein binding; cattle are most susceptible
toxicokinetics of dicoumarol
well absorbed, readily crosses placent, half-life of 54 hours in cattle, 23 hours in sheep; blood levels decline rapidly while liver levels remain elevated for longer
clinical manifestations of dicoumarol
massive hemorrhage, animals continue to eat until late stage, HR and RR elevated, pale MM, prolonged CRT, hematomas, abortion (fetus is more susceptible), neonatal death, CNS disturbance, dyspnea
clinical pathology of dicoumarol
anemia, normal WBC, elevated clotting time, elevated prothrombin time
diagnosis of dicoumarol
elevated prothrombin time, analyze tissues for dicoumarol (dicoumarol can pass in milk)
treatment of dicoumarol
remove suspected feed (dilution is ineffective), blood transfusion, vitamin K
recommendations for feeding sweet clover to cattle
don’t feed to pregnant animals in last trimester, feed rotation, routine blood monitoring, withdrawal of 6 weeks before dehorning etc., don’t ship cattle until clotting times have returned to normal
what fungus is fumonisin (mycotoxin) produced by
fusarium (corn)
susceptibility to fumonisin toxicity
horses are most susceptible
mechanism of action of fumonisin toxicity
interfere with biosynthesis of sphingolipids causing decreased membrane stability
clinical manifestations of fumonisin toxicity in horses
equine leukoencephalomalacia – depression, blindness, ataxia, circling, wandering, facial paralysis, swallowing problems, head pressing, death in 1-3 days
clinical manifestations of fumonisin toxicity in pigs
dyspnea, cyanosis, weakness, death in a week
diagnosis of fumonisin toxicity
elevated liver enzymes, bilirubin, cholesterol and BUN; WBC and protein in CSF
PM of fumonisin toxicity
necrosis and malacia of cerebral white matter, hemorrhage in white matter, liver necrosis and apoptosis, kidney nephrosis, pulmonary edema (pigs)
treatment of fumonisin toxicity
none specifically; neuro damage is irreversible
toxicokinetics of oil poisoning
most are lipophilic and are readily absorbed by all routes including respiratory
mechanism of action of oil poisoning
irritation, GIT dysfunction through stimulation or microorganism alteration, bonemarrow suppression
clinical manifestations of oil poisoning
aspiration pneumonia (oil is 100 fold more toxic if inhaled so causes ciliary and cough function to not work), lipid pneumonia (WBC skyrocket), bloat, anorexia, weight loss, ketosis, oil smell in rumen (float contents), dyspnea, ataxia, incoordination, abortion, elevated BT
clinical pathology of oil poisoning
leukopenia followed by a neutrophilia (use to tell when exposed), anemia, marrow depression, elevated BUN/liver enzymes
PM of oil poisoning
evidence of oil in rumen, bloat, GIT irritation, mild degeneration of liver, nephrosis, pulmonary congestion and consolidation, pulmonary abscesses, fibrinous pleuritis, dermal irritation
other concerns regarding oil poisoning
milk taint and meat residues, low vitamin E/A, impaired reproduction, cancer, endocrine disruption
treatment of oil poisoning
activated charcoal, mineral oil, antibiotics for secondary infection; bathe wild life with detergent to remove oil and prevent hypothermia; do not induce vomiting
toxicokinetics of coal tar and phenol compounds
well absorbed orally and reasonably through the skin; metabolized in liver by glucoronidation so cats are more susceptible
mechanism of action of coal tar and phenol compounds
protoplasmic toxicant causes liver necrosis and renal tubular necrosis; ingestion of clay pigeons by swin results in hemorrhagic hepatitis
clinical manifestations of coal tar and phenol compounds
sudden death with high dose; low to moderate dose – anorexia, depression, weakness, tremors, jaundice, secondary anemia, possible photosensitization
PM of coal and phenol compounds
necrosis and ulceration of skin, enlarged pale kidney with tubular necrosis, centrilobular degeneration and necrosis of liver, icterus
clinical pathology of coal and phenol compounds
proteinuria, hematuria, epithelial cells/casts, elevated liver enzymes
diagnosis of coal and phenol compounds
pathological and circumstantial information
treatment of coal and phenol compounds
activated charcoal and wash skin with detergent; gastric lavage; vitamin E
two groups of chemicals in polyhalogenated biphenyls
PBB (more toxic) and PCB
why were PBB and PCB banned
embryotoxic, teratogenic, carcinogenic, immunosuppressive, residues, potent enzyme inducers
mechanism of action of PBB and PCB
enzyme induction; degenerative and membrane changes in variety of tissues
clinical manifestations of PBB/PCB toxicity in dairy cattle
insidious vague onset, weight loss, reduced milk production, abnormal hoof development, atrophy of udder, increased urination and lacrimation, hematomas, thrombocytopenia, abscesses, metritis, abortion, prolonged gestation, alopecia, chloroacne
PM of PBB/PCB toxicity
emaciation, thymic atrophy, heptaic fatty change, renal tubular degeneration, ascites
treatment of PBB/PCB toxicity
slaughter and disposal because of residue and reproductive effects; burning is best way
factors influencing fluoride toxicity
amount ingested, duration of exposure, solubility, age (young and fetus are more susceptible), nutritional status (high Ca protective), stress
toxicokinetics of fluoride toxicity
well absorbed, cumulative poison (predisposition to calcified tissues), fetus accumulates
mechanism of action of fluoride toxicity
delays and alters normal mineralization of bones and teeth
clinical manifestation of acute fluoride toxicity
symptoms within 30 minutes, irritation, colic, saliva, vomiting, hemorrhagic gastroenteritis, stiffness, muscle weakness, convulsions, cardiac failure
chronic fluoride toxicity manifestations
lameness, stiffness, unthrifty, mottled brownb and uneven tooth enamel, exostoses, lapping of water due to dental pain
diagnosis of fluoride toxicity
history of lameness and dental problems; usually a herd problem
treatment of fluoride toxicity
prevent with administration of aluminum salts at 10x the level of fluoride
characteristics of ammonia gas
strong base and highly irritant/caustic; generated from sewage pits or fertilizer with no smell
mechanism of action of ammonia gas
ammonium hydroxide is formed in lungs causing damage
manifestations of acute exposure to ammonia gas
coughing, dyspnea, pulmonary edema, lacrimation, poultry with opacity in eyes (blinding)
treatment of ammonia gas toxicity
improve ventilation
nitrogen oxide gases characteristics
highly toxic, NO2 and N2O4 are at equilibrium with each other
mechanism of action of nitrogen oxide gas toxicity
react with moist membranes of lung tissue to form nitric acid –> caustic properties of nitric acid cause irritation, pulmonary edema and direct alveolar damage; methemoglobin can also be produced
clinical manifestation of nitrogen oxide gas toxicity
dyspnea, coughing, salivation, lacrimation, reddened MM, bronchitis, emphysema, secondary bacterial infection
treatment of nitrogen oxide gas toxicity
improve ventilation
where are sulfur oxide gases produced
industrial sources such as high sulfur coal or oil combustion
mechanism of action of sulfur oxide gas toxicity
sulfur reacts with water in lungs to form sulfuric acid that has a caustic effect leading to irritation, pulmonary edema, hemorrhage and emphysema
clinical manifestations of sulfur oxide gas toxicity
lacrimation, salivation, coughing, bronchoconstriction, cyanosis, red MM
PM of sulfur oxide gas toxicity
pulmonary edema, emphysema, atelectasis, hemorrhage, fibrosis, secondary bacterial pneumonia
treatment of sulfur oxide toxicity
remove from contaminated area
characteristics of hydrogen sulfide gas
extremely toxic; one breath can kill; smells like rotten eggs (but rapidly destroys sense of smell)
what four major gases do sewage pits produce
hydrogen sulfide, ammonia, carbon dioxide, methane
mechanism of action of hydrogen sulfide (3)
irritation (reacts with Na to for Na2S that produces pulmonary edema); enzyme inhibition of cytochrome oxidase enzyme causing cellular respiration to stop (hypoxia); binds with hemoglobin to produce sulfhemoglobin
clinical manifestations of hydrogen sulfide gas
coughing, lacrimation, pulmonary edema,dyspnea, bronchoconstriction, cyanosis, anoxic terminal convulsions
PM of hydrogen sulfide gas toxicity
few gross lesions; may smell hydrogen sulfide on tissues
treatment of hydrogen sulfide gas toxicity
ventilation, oxygen
mechanism of action of carbon monoxide
rapidly absorbed and reacts quickly with hemoglobin to form carboxyhemoglobin
clinical manifestations of carbon monoxide toxicity
CNS excitation to depression, disorientation, muscle weakness, elevated HR/RR, dyspnea, bright red blood and MM (dissipates over time), coma and death
treatment of carbon monoxide toxicity
high levels of oxygen to displace CO from hemoglobin; avoid respiratory stimulants because increase oxygen demand
examples of anionic detergents
laundry detergent, dishwasher detergent, shampoo
anionic detergent toxicity and absorption
slight-moderate toxicity; well absorbed orally, does not penetrate intact skin;
clinical manifestations of anionic detergent toxicity
dermal irritation and blistering can occur; vomiting and diarrhea; ocular exposure can cause corneal erosion and opacity
treatment of anionic detergent toxicity
oral administration of milk/water to dilute, activated charcoal, wash, alkalinization of urine to prevent renal damage
examples of cationic detergents
fabric softeners and sanitizers; highly toxic
absorption of cationic detergents
well absorbed orally but poor dermal absorption
clinical manifestation of cationic detergent toxicity
vomiting, salivation, muscle weakness, fasciculations, CNS or resp depression, corrosive damage to MM, hairloss, skin ulcers
treatment of cationic detergent toxicity
milk or egg whites, activated charcoal, saline cathartic, fluids; emetics are NOT recommended
non-ionic detergents
mild irritation and low toxicity; diarrhea and vomiting, treat with milk or water
what molecule does bleach contain
sodium hypochlorite – not very stable molecule
manifestations of bleach
corrosive on skin and MM; oxidative damage; reacts with stomach acid to produce chlorine gas that animal can inhale causing pulmonary edema (dyspnea, shallow breathing, cyanosis) – bleach also can react with ammonia to make chloramine gas
treatment of bleach exposure
wash, milk of magnesia, milk or water; emetics are contraindicated
long term effects of bleach exposure
pulmonary fibrosis, esophageal stenosis, secondary infections
what body systems does ethanol effect
GIT and CNS
effects of isopropanol
severe CNS depression within 1 hour, respiratory depression; acetone the primary metabolite produces a ketosis
treatment of isopropanol toxicity
emetics are useful within 1-2 hours of ingestion; fluids with bicarb; activated charcoal in INEFFECTIVE
mechanism of action of methanol
metabolized by alcohol dehydrogenase to formaldehyde then formic acid
clinical signs of methanol
CNS depression, ataxia, hypothermia, respiratory depression
toxicokinetics of pine oils and turpentine
readily absorbed, can be detected on breath, metabolized by liver with glucoronidation (cats more susceptible)
clinical signs of pine oils exposure
erythema on exposed MM, tearing and photosensitivity with eye exposure (+inflammation), weakness, CNS depression, ataxia, nausea, salivation, bloody vomiting, aspiration pneumonia can be subsequent to vomiting, hypotension
specific signs observed in cats with pine oil exposure
pulmonary edema, centrilobular hepatic necrosis, renal cortical necrosis
treatments of pine oil and turpentine exposure
milk, egg whites, water; activated charcoal and washing; emetics are contraindicated
Naphthalene toxicity (moth balls)
cats are most susceptible;
Naphthalene clinical signs
vomiting, methemoglobinemia, hemolytic heinz body anemia, hemoglobinuria, liver and kidney damage
treatment of naphthalene toxicity (moth balls)
emesis, activated charcoal, saline cathartic, methylene blue
Para-1,4-dichlorobenzene toxicity (moth ball)
insecticide; vomiting, pain, tremors, seizures; liver and kidney damage
treatment of para-1,4-dichlorobenzene toxicity
activated charcoal, symptomatic, sedation
what do most drain and oven cleaners contain
Na and K hydroxide
effect of drain and oven cleaners
extremely toxic to skin and MM – coagulation to liquefactive necrosis; can have severe necrosis of esophagus leading to stricture
treatment of drain and oven cleaner exposure
diluted vinegar to neutralize base; emetics and gastric lavage are contraindicated
toxic agent in matches and fireworks
potassium chlorate – strong oxidizing agent
clinical manifestation of matches and firework exposure
vomiting, CNS depression, cyanosis, intravascular hemolysis, methemoglobinuria
treatment of matches and firework exposure
vitamin C – slow acting; emetics and gastric lavage
what other than potassium chlorate do fireworks contain
nitrate and perchlorate salts that can cause GIT irritation, vomiting, salivation, pain
