Plant Related Toxicants: Nitrate, Cyanide, Soluble Oxalates (Shokry) Flashcards
How do plants accumulate nitrate?
Nitrate is absorbed from soil
Nitrate (NO3) → Nitrite (NO2) → ammonia (NH3) → amino acids and vegetable protein
Nitrate to nitrite conversion rate slower than uptake from soil → accumulation
What factors favor plant nitrate accumulation?
- Plant species: sweet clover, alfalfa, wheat, corn
- Content and form in soil: high nitrate or ammonia
- Soil conditions: moisture, acidic, low Mb/S/P, low temp, soil aeration, drought
- Decreased light reduces nitrate reductase activity
- Phenoxy acetic acid herbicides increases accumulation (improve palatability, increase toxin)
What are the nitrate accumulating plants?
- Pigweed
- Oat
- Beet
- Johnson grass
- Corn
- Lambs quarters
- Sweet clover
- Alfalfa
- Wheat
- Sunflower
What are sources of nitrite toxicity?
- Forages/hays containing high amounts of nitrate
- Accidental ingestion of contaminated feed or water
- Overdose with nitrite IV (vasodilator)
What is the LD50 of nitrate for ruminants?
0.5-1 g/kg
Need huge amount for toxicity
What species are the most susceptible to nitrate poisoning?
Ruminants
Is nitrite or nitrate more toxic?
Nitrite is 10x more toxic than nitrate
A forage nitrate greater than _____% can cause acute toxicosis
1
T/F: young ruminants are more susceptible than adults to nitrite toxicity
FALSE
Young animals are more resistant because they have not developed the rumen microflora to convert nitrate to nitrite
Monogastrics are also more resistant because they do not have the microflora
What types of diseases will cause increased nitrate toxicity?
- Anemia
- Methemoglobinemia
How is nitrate normally used in the body? When do you see accumulation
Nitrate → nitrite → ammonia → amino acids → vegetable protein
Accumulation occurs when the rate of conversion of nitrite to ammonia is slower than the rate of conversion of nitrate to nitrite
What body system does nitrite ion affect?
Erythrocytes
Nitrite ion enters the erythrocytes in exchange for chloride ion (can also cross placental and enter fetal erythrocytes)
What is the MOA of nitrite?
One nitrite interacts with two hemoglobin → oxidation of ferrous iron (+2) to ferric (+3) and conversion of hemoglobin to methemoglobinemia
Lack of oxygen carrying capacity → Anoxia
In chronic nitrate toxicosis, abortion occurs due to decreased ___________ but in the acute toxicosis, abortion occurs due to _______
Progesterone; methemoglobinemia
What lesions do you see in nitrate poisoning?
- Brown-chocolate color of the blood
- Congestion of organs
What clinical signs are observed in nitrate toxicosis?
Sudden death
Rapid breathing, restlessness, apprehension, dyspnea, weakness, ataxia, sternal recumbency, cyanosis, terminal convulsions
What would you do to diagnose nitrate toxicity?what is the specimen for choice?
Chemical analysis
- Forage, hay, water
- Ocular fluid for animals that have been dead for several hours
Methemoglobinemia concentration
What specific test can qualitatively determine presence of nitrate?
Diphenylamine test
- Positive result (dark blue color) indicates >5000ppm nitrate
What is the DDX for methemoglobinemia and anoxia?
Agents causing methemoglobinemia:
- Nitrate and nitrite
- Copper
- Acetaminophen
Agents inhibit oxygen utilization of tissues:
- Cyanide (bright red blood)
- Hydrogen sulfide (dark blood)
Hemolytic agents:
- Copper, zinc, naphthalene, bromate, iodate, arsine gas, onion, mustard, red maple, gossypol, snake venom, other
Carbon monoxide (bright red blood)
Cardiac toxicants:
- Digitalis, magnesium, calcium, potassium, flouroacetate in herbivores
What is the treatment for nitrate toxicity?
Methylene blue IV for ruminant and monogastrics (except cat) as a reducing agent
Activated charcoal, ruminal lavage with cold water, oral antibiotics
What are some cyanogenic plants?
Large animals:
- Wild cherry
- Sudan grass, Johnson grass and sorghums (fall grasses; also accumulate selenium, nitrate, and cyanide)
Small animals:
- Cherries, apples, plums, apricots
- Some species of lima bean, cassava roots (tapioca)
What is usually the source of cyanide toxicity in small animals?
Hydrogen cyanide and cyanide salts:
- Fumigant rodenticides
- Fertilizers
- Sodium nitroprusside (used as hypotensive)
- Combustion of plastic compounds (produce HCN gas)
- Cyanogenic plants
Cyanogenic plants contain ______________ that can liberate toxic amounts of HCN.
Cyanogenic glycosides
What is the characteristic odor of cyanide?
Bitter almond or ammonical
Probably not a good way to diagnose if you want to continue living
Thiocyanate SCN, a metabolite of cyanide, has a ___________ effect.
Antithyroid
Only see effects in chronic toxicosis
What species are most susceptible to cyanide poisoning?
Ruminants (cattle> sheep) > horse> swine
Hydrolysis by rumen microflora causes release of cyanide from cyanogenic plants
T/F: Plant damage like wilting, frost, or drought decreases cyanide toxicity.
False
INCREASE toxicity → release β-glucosidate → hydrolysis of cyanogenic glycosides → release cyanide
What part of the plant has the highest concentration of cyanide? How does this compare to nitrate accumulation?
Cyanide: seeds > leaves > bark > stems and fruit
Nitrate: stems/stalks > leaves > seeds (grain)
Will young or old plants accumulate more glycosides?
Young
Same as nitrate accumulation in plants
Where is HCN is absorbed from?
- GI tract
- Inhalation
- Intact skin
Where is HCN metabolized and then excreted?
Liver and serum metabolism: CN-in presence of thiosulfate → thiocynate (SCN⁻, excreted in urine) by sulfurtransferase
Small amounts of HCN excreted in urine or expired air
What is the MOA of cyanide?
Excess CN- binds with ferric iron and cupric copper to mitochondrial cytochrome oxidase → block electron transport chain → unable to use oxygen resulting in histotoxic anoxia (brain and neuronal damage)
- Metabolic acidosis due to anaerobic glycolysis
- Vasoconstrictor effect
- Irritant to mucus membranes
What are the clinical signs of acute cyanide poisoning?
- Rapid onset (death in 4-5 minutes from CS onset)
- May not show any clinical signs before death
- Tachypnea, apparent anxiety, severe panting, gasping, and behavioral alarm
- Salivation, muscle tremors, lacrimation, urination, defecation, colic, vomiting, prostration, bright red mucous membranes (hyperoxygenation), clonic convulsions, rapid death
What are the clinical signs of chronic cyanide poisoning?
Posterior paralysis, urinary incontinence, and cystitis/constipation due to lower spinal cord degeneration
Goiterogenic effect (due to low levels of thiocyanate)
What are the specimens of choice for determining cyanide poisoning?
Forage (200 ppm = toxic), blood (stays longer in tissues), rumen content, liver, muscle, brain and heart
- Brain, heart = best specimens
All (except blood) should be frozen immediately and kept frozen
Elevated levels of thiocyanate can be found in ____________.
Urine
What commercial test can help detect toxic levels of cyanide in rumen contents of plant?
Sodium picrate paper test
- Yellow color changes to brick red for positive test
What lesions do you see due to cyanide poisoning?
- Bright red mucus membranes
- Cherry red blood (may not clot or slowly clot)
- GIT and lung congestion w/ petechial hemorrhage possible
- Cyanide smell may be present (leaves the rumen contents quickly)
What is the DDX for cyanide poisoning?
- Carbon monoxide (bright red blood)
- Hydrogen sulfide (rapid tissue death due to anoxia but tissues are dark green-purple)
- Nitrate (blood is brown-chocolate color)
- Urea (few lesions but causes colic, nervous behavior, ammonia odor)
How do you treat cyanide toxicity?
Sodium nitrite 20% IV:
- Immediately improve perfusion by vasodilation
- Causes methemoglobinemia which can bind the CN- and reactivate cytochrome oxidase
Sodium thiosulfate 20% IV:
- Convert CN- to thiocyanate (less toxic, urinary excretion)
- Oral sodium thiosulfate
- Oxygen therapy
- Vinegar and cold water to slow microbial hydrolysis
- Mineral oil as laxative
What plants contain large amounts of soluble oxalates?
- Pigweed
- Beet
- Lamb quarter
- Halogenton
- Sorrel, dock
- Rhubarb
- Sorrel, soursop
- Greasewood
- Star-fruit
What are the sources of soluble oxalates poisoning?
- Plants
- Potassium and sodium oxalate in household cleaners
- Fungi
- Ethylene glycol
What species are most susceptible to soluble oxalate toxcity?
Sheep and cattle
What is accommodation of the rumen microflora for oxalates?
Ruminants allowed to graze on small quantities of oxalate contains plants gradually results in detoxification of up to 70% more soluble oxalates than normal
What part of the plant contains highest amounts of soluble oxalates?
Leaves > seeds > stems
A diet rich in __________ decreases oxalate toxicity by making insoluble oxalates which cannot be absorbed.
Calcium
Binds to make calcium oxalate
How are soluble oxalates metabolized in the rumen?
To carbonates and bicarbonate
What is not metabolized is absorbed to the blood and may affect serum tissue calcium
What is the MOA of soluble oxalates?
Soluble oxalates combine with Ca to form insoluble Ca oxalate
→ hypocalcemia and tetany in acute cases
→ affect bone and milk production in lower levels
→ precipitation of crystals in kidney → kidney damage and necrosis
→ starfruit also has caramboxin (neurotoxin that acts as glutamate agonist)
What are the clinical signs associated with soluble oxalate?
- Colic, dullness, depression, muscle twitching//weakness
- Head and neck pulled to one side in sheep (seen in milk fever in cattle)
- Prostration, coma, death
- Rapid breathing and blood tinged froth at mouth
- Convulsions
Animals that do not die from acute form of soluble oxalate poisoning develop what signs?
Fatal renal tubular toxicosis and signs of oligura, depression, hyperkalemia, and cardiac failure
Chronic tubular necrosis and polyuria
What lesions are present due to soluble oxalate poisoning?
- Plant in rumen
- Excess fluid in abdominal and thoracic cavities, petechial hemorrhage in GI mucosa
- Emphysema of lungs with aspirated ingesta
- Esophagus and mouth with blood tinged froth
- Kidney with dark cortex and medulla separated by gray line from accumulation of oxalate crystals in tubules
How can you make a laboratory diagnosis of soluble oxalate poisoning?
- Presence of Ca oxalate crystals in kidney tubules
- Hypocalcemia
- High BUN
What is the DDX for soluble oxalate toxicosis?
- Rumen acidosis (but pH of rumen with oxalate is alkaline)
- Milk fever (lacks oxalate lesions)
- Hypocalcemia
What is the treatment for soluble oxalate toxicosis?
Usually of little value once CS appear
- Activated charcoal or limewater (prevent absorption)
- Calcium gluconate IV slowly (may cause transient improvement)
- Saline glucose (treat alkalosis and cause diuresis)
- Supplement calcium salts or Ca-rich diet
- Supportive therapy for nephrosis
