Exam 2- Feed, ionophores, etc. Flashcards
Sodium ion toxicosis- water deprivation causes
Extensive periods without water followed by unrestricted access. Swine are the most commonly affected species.
Cattle: restricted water
Dogs: cured meats, homemade playdough, sea water
Sodium ion toxicosis- mechanism of action
Na+ moves into neurons with dehydration -> increased brain Na+: decreased glycolysis -> decreased energy in neuron -> ATPase pump impaired -> Na+ unable to escape -> unrestricted water acess -> H20 moves into neurons -> edema and brain swelling
Sodium ion toxicosis clinical signs
Swine: rapid onset, thirst, constipation/dry feces, recumbent and paddling, blindness, head pressing, jaw chomping
Cattle: tremors, ataxia, recumbent and paddling, circling
Dogs: GI upset, vomiting, diarrhea, PU/PD Tremors
Sodium ion toxicosis sample collection and testing
Brain: Fresh brain Na+ Swine- Eosinophilic perivascular cuffing
Cattle- edema and neuronal degredation (polio)
Dogs: eosinophils and necrosis not present
Occular fluid
CSF and serum
sodium ion toxicosis treatment
shut off water
Rehydrate slowly- alternate water flow off/on
Use of hypertonic solution preferred to prevent further edema
Mannitol (25%) for edema
Furosemide- 2.2 to 4.4mg/kg PO, IV, or IM BID
Definition of an Ionophore
A substance that can transport ions across a lipid membrane within a cell
Feed efficiency and improved growth
Coccidiostat
Positive effects of ionophores
Improve feed efficiency- reduce gram + & favor Gram - bacteria
change in gram-/gram+ ratio (increasing proprionic acid- morei efficient energy)
Protein metabolism and energy is positively influenced
Ionophores and Mechanism of Action
Overdose -> hemostatic mechanisms fail resulting in an increase of Ca and Na influx.
Increased Ca influx -> Free radical formation -> oxidative damage to tissues
tiamulin potentiation: Directly inhibits CP450 enxzymes. Inhibition of the enzymes causing ionophore accumulation, and additional oxidative damage to tissues - eventual muscle necrosis
Monensin Toxicity
horses are the most susceptible species.
what are Causes of intoxication associated with Ionophores?
Mixing errors, delivery errors, history of eating cattle feed (dogs)
Barn break ins
Why are ionophore intoxications often mis-diagnosed in large animals
Delayed onset of clinical signs
Subtle/non-specific signs
Clinical signs of Ionophore toxicosis in horses
Anorexia, sweating, colic, progressive ataxia, posterior paresis, laterally recumbent, tachycardia, hypotensive
Death (within 24 hours)- can be delayed
Clinical signs of ionophore intoxication in cattle
Anorexia, diarrhea, weakness/ataxia, recumbent, dyspneic, death (2-5 days)
clinical signs are several days after exposure
Clinical signs of ionophore intoxication in Swine
Dog sitting, unable to rise/move, increased vocalization, centrally aware, anorexia, tremors
clinical Signs of ionophore intoxication in Dogs
Flaccid ascending paralysis
High dose results in respiratory paralysis
Alert
Appears like botulism
Clinical Signs of ionophore intoxication in Poultry
Anorexia & diarrhea, weak & ataxic, Drooped head & wings, Sternal recumbency, paralysis
ionophore sample collection and testing
Cattle and horses:
cardiac and skeletal muscle (left papillary muscle)
Swine, sheep, dogs: Skeletal muscle (diaphragm is a good muscle)
Collect muultiple sections!!! Cut into muscle-> never know what you wind
Feed- test for ionophores
Clincal pathology in ionophore intoxication cases
leukocytosis
Increased cardiac troponins, Increased AST, CPK, Protein
Decreased K, NA, Ca
urine: increased Glucose, protein, myoglobin, hemoglobin
Decreased USG
Lesions associated with Ionophore intoxication
Myocardial necrosis
Skeletal muscle necrosis
ascited, hydrothorax, pulmonary edema, hepatic congestion
Lesions associated with ionophore intoxication and Poultry
Cardiac and skeletal muscle necrosis Pulmonary and hepatic edema Gastroenteritis Ascites and hydro pericardium Gross lesions are not commonly observed
tiamulin and ionophores
Tiamulin is a common antibiotic utilized in swine to treat respiratory disease
Inhibits metabolism of ionophore: accumulation results in toxicosis
situations:
tiamulin in water + ionophore in feed
tiamulin + ionophore in feed
Tiamulin + other ionophore
Diagnosis of ionophores
History of exposure
Corresponding clinical signs and lesions
Presence of ionophore in feed
Treatment of ionophore intoxication
Remove source No antidote Reduced stress (decrease cardiac load) Vitamin E/Selenium(limits oxidative damage, doesn't reverse damage) (Vitamin E would be the safer option, because Selenium has a narrow margin of safety)
Prevention of ionophore intoxication
Good milling practices
Correct storage of materials
communication- make sure the correct feed is going to the right place
Gossypol intoxication source
cotton seeds
Gossypol mechanism of action
speculated:
Inhibition of protein synthesis
Disrupts ETC -> tissue degeneration & necrosis
Decreased reproduction through inhibition of spermatogenesis
chelates iron- binds to iron in egg yolk
Gossypol species susceptibility
Monogastrics and pre-ruminants are more susceptible than adults
calves- heart failure
Ruminants & horses- generally resistant
Clinical signs associated with Gossypol intoxication
Affects are cumulative
swine- slow growth, weakness, dyspnea, generalized edema, death
Pre-ruminants- sudden deaths
Dogs and bulls- decreased fertility
Dairy cattle- ill thrift, decreased heat tolerance, decreased fertility
Sample collection associated with Gossypol intoxication
Heart, liver, lungs
What gross lesions are there asssociated with Gossypol intoxication
Widespread congestion & edema (ascites, hydrothorax)
Heart- enlarged, pale, streaking
Liver- pale, friable, and swollen
Skeletal muscles may be pale
Microscopic lesions associated with Gossypol intoxication
heart- myocardial degeneration and necrosis
Lungs- interlobular edema
Liver- centrilobular hepatic necrosis
Diagnosis of Gossypol intoxication
Presence of gossypol in feed- test for the free form
History of exposure
Treatment for Gossypol intoxication
Remove source form diet (reproductive effects reversed)
Decrease stressors
Supplementation: Iron, protein, Vitamin A, Lysine
Urea/Non-Protein Nitrogen sources
Feed, fertilizers
Urea metabolism and positive effects
Normal
urease rapidly converts urea to ammonia
Ammonia synthesized to microbial protein by the rumen microbes.
in an alkaline environment, Ammonia is absorbed into the blood stream. -> Liver -> Urea -> Urine
In acidic environment, ammonia is converted to ammonium - not absorbed into the blood stream
urea MOA
In an intoxication situation
Urease hydrolyzes urea ato ammonia in the rumen. H+ protonates ammonia to ammonium and the pH begins to increase (alkaline pH results in ammonia being favored)
Ammonia is absorbed into the blood
Excessive ammonia overwhelms the liver, and can’t convert to urea
Elevated blood ammonia crosses the BBB
what are the conditions of optimal activity for Urease
Potential methods for intervention
Temperature 120 degrees F
pH 7.7-8.0
Peak NH3 .5-2hrs
Treatment: cool the rumen down, and make the diet more acidic
Casues of Urea/Non-Protein Nitrogen intoxication
Feed associated- misformulations/excess, Direct feeding of protein pellets etc.
Urea based fertilizers
Water- fertilizer tanks used for water
Predisposing factors to Urea/Non-Protein Nitrogen intoxication
poor carbohydrate diet: Decreased energy for rumen bacteria resulting in a decreased conversion of ammonia to protein
Inadequate adaptation- rumen microbes not accustomed to high amounts
high rumen pH and temp- optimal conditions for urease -> increased conversion to ammonia
Heaptic insufficiency- capability to eliminate ammonia from blood
Unrestricted access to supplements
Clinical signs associated with Urea/Non-Protein Nitrogen
Rapid onset: 10 min- hours post consumption Salivation & bruxism (grinding) Muscle tremors and incoordination Polyuria Weakness Tachypnea Violent spasms/seizures Acute death - often found this way
Urea/Non-Protein Nitrogen Sample Collection and testing
Ocular fluid (post mortem sampling)
rumen content
Serum
water
Feed or forage- urea concentration
time is of the essence- collect, seal, and freeze samples ASAP following death
Treatment for Urea/Non-Protein Nitrogen intoxication
Stop further ammonia production
Decrease urease activity (decrease temp and acidify rumen contents)
Triage (urinarination = still converting ammonia to urea = improve prognosis)
consumption of Raw soybeans is associated with:
ammonia toxicosis Lactic acidosis (acute carbohydrate fermentation
Clinical signs associated with Consumption of Raw soybeans
Lethargy, depression, salivation, polyuria, increased RR, death
Diagnosis of overconsumption of Raw soybeans
history of exposure
Elevated rumen or ocular ammonia
Treatment for overconsumption of Raw soybeans
Treat the ammonia toxicosis
>8hrs post ingestion- treat carbohydrate overload and rumen acidosis
Ammonated forages common term
Bonkers syndrome
Mechanism of action for Ammonated forages
Imidazoles form from browning reaction with amino groups and a reducing compound (sugar)
Reaction is more rapid at higher temps and pH
Multiple imidazoles form
Clinical signs associated with Ammonated forages
trembling Stampeding I"nterupted periods of calm Dilated pupils Rapid respiration urination, salivation, defecation Bellowing and seizures Star gazing
Diagnosis for Ammonated forages
Remove feed- rapid recovery
Assay for imidazoles in forage, milk, or serum- not routinely offered. Gross lesions consistent with traum
Treatment for Ammonated forages
Sedatives, thiamine
Nitural toxicants in Feed
Nitrate and cyanide
Nitrate sources
Plants- forage material- nitrate accumulators
Stunted planted growth causes accumulation over time
Stressors- drought/dry weather, increased manure etc.
where on the corn stalk do you find the highest concentrations of Nitrate
The lower on the stalk, the higher the Nitrate
Nitrite sources
Fertilizer, pickling and curing brines, gunpowder, explosives
Nitrate MOA
Nitrate becomes nitrite - some is converted to ammonia and is used for microbial growth
Excessive nitrate - increases nitrite -> Excessive nitrite overwhelms bacteria.
nitrite in the blood causes an accumulation of methemaglobin
Death by anoxia- blood appears chocolate brown
What animals are most susceptible to Nitrate toxicity
Ruminants are most susceptible- rumen microflora rapidly converts nitrate to nitrite.
horses pigs dogs and humans are RESISTANT to nitrate
What animals are most susceptible to nitrite toxicity
All sepecies are susceptible to ingetion of nitrite because nitrite enters the blood stream.
Predisposing factors to nitrite intoxication
Rate of consumption- small amounts ingested over time does not necessarily result in intoxication
Low energy diets (decreased energy for rumen bacteria results in a decreased conversion of nitrite to ammonia)
Lack of adaptation- rumen microbes not accustomed to high amounts = overwhelmed
Clinical Signs associated with nitrate intoxication
Rapid onset- within minutes to several hours
Cyantoic, weakness & ataxia, collapse, respiratory distress, aboritons , death
Sample Collection & testing for Nitrate
Ocular fluid… aqueous OR vitreous
>20ppm indicates poisoning
feed and forage- Nitrate/Nitrate on a dry matter masis
Water- fertilizer tanks, wells, ponds
Lesions associated with nitrate
Tissues may appear congested and muddy
Diagnosis of Nitrate intoxication
Chocolate brown blood, history of exposure, high ocular fluid or serum nitrate/nitrite concentrations, Detection fo high nitrate/nitrite levels in suspected materials
Bovine abortions: Fetal ocular fluid nitrate >20ppm
Traetment of Nitrate intoxication
Prevent further exposure
Methylene blue 1% (repeat as needed every 6-8 hours0
Cold water and oral penicillin: Decreased rumen microbe activity-> Decreased nitrate reduction to nitrite
Prevention of nitrate intoxication
provide readily utilized energy source
Introduce ruminants to high risk forages slowly
ID and understand the major sources and circumstances for nitrate risk
what human health concerns are there with nitrate toxication?
Blue Baby syndrome: methemaglobinuria
Cyanide sources
fumigants, pesticides, cyanide salts, fires, plants
Cyanogenic Plants
Bamboo, Elderberry, Apricots, Cherries, Clovers
When is the greatest cyanide potential in forages
During the early growth phases, and then declines
Cyanide in forages
physical damage to the plant, causes the release of intrinsic enzymes -> Hydrolyze CG -> HCN. Toxic levels of HCN may remain in large hay bales where forage is immediately baled
Properly ensiled silage loses cyanide potential
Cyanide in Plants
Thiosulfate combines with HCN -> thiocyanate -> urinary excretion. Animals can safely consume small amounts of these plants
ruminants constantly exposed: Effects are NOT cumulative -> tolerance does not develop
need a severe overload
MOA of cyanide
Occurs within the mitochondira
cyanide ion combines with Fe in cytochrome oxidase system-> inhibits reducetion of O2 within ETC -> inhibited transfer of O2 to tissues. -> Inhibited cellular respiration -> anoxia
What species are at risk for cyanide toxicity
Ruminants- higher risk: rumen microbes - rapid hydrolysis of CGs to HCN
Monogastrics - lower risk: lower gastric pH -> decreased hydrolysis of CGs. Must consume raw plant material
All species are susceptible to cyanide gas
Clinical signs associated with Cyanide
Rapid onset: minutes to <1 hr
Anoxia, dyspnea, excitement & muscle tremors, collapse, seizures -> death,
Bright cherry red mucous membranes
Sample collection and testing for Cyanide
Whole blood- bright red venous blood, rumen stomach contents (almost odor)
Brain, liver, forage/plant material
Treatment for Cyanide
Must have rapid intervention
Sodium nitrite combination with sodium thiosulfate
mehtylene blue can be utilized as well- use when you suspect either cyanide or nitrate intoxication
Mechanism: Na Nitrite -> methemablobin -> CHMetHb -> Cn binds to thiosulfate -> excreted as thiosulfate
what human health concerns does Cyanide have?
Gasseous form is used as a terrorist/warfare agent
