Gastrointestinal Toxicology Flashcards
Why is it difficult to determine the cause of GI injury?
- many conditions that cause GI signs are not toxic in nature
- a wide array of poisons affect the GI system
- animals exhibit GI signs secondary to other diseases/toxicoses (liver, kidney, neurologic)
What are the main 6 mechanisms of direct GI injury?
- irritation
- corrosion
- impaired mucosal blood supply
- impaired nutrient or water absorption
- epithelial cell necrosis
- altered motility
What are the main clinical signs associated with GI toxicosis?
- anorexia, salivation, diarrhea in all species
- colic, cramps, abdominal pain
- vomiting in cats and dogs
- regurgitation in ruminants and birds
What lectins cause GI toxicosis? What is the most common sources? What produces the most potent ones?
hemaglutinins, toxalbumins
mostly beans and other plants, like Jahtropha, Robina, Momordica, Hura, and Sophora
Ricinus communis (castor bean) —> ricin (white powder) and abrin
What is toxicity to lectins associated with? What species are affected?
ingestion and chewing of seeds, destroying the seed coat and releasing lectins —> poorly absorbed in the GIT
MANY: dogs, poultry, wild fowl, pigs, horses, sheep, goats
What are the 4 toxic principles of lectin? Which ones are cytotoxic? Why?
- ricin*
- abrin*
- ricine
- ricinus communs agglutinin
contain A and B chains linked by a sulfide bond
- A inactivates eukaryotic ribosomes and impairs peptide elongation —> inhibits protein, DNA, and RNA synthesis
- B binds to galactose-containing glycoproteins and glycolipids on the surface of cells facilitating the entry of ricin into cytosol
What are the 3 specific actions of ricin on the GIT? How can it affect the CVS?
- irritates GIT mucosa
- impairs nutrient absorption and cell viability
- inhibits protein synthesis in GI epithelial cells
disturbs calcium homeostasis by decreasing calcium uptake by the sarcoplasmic reticulum and increases Na/Ca exchange
What effect do ricinine and ricinus communis agglutinin found in lectin have?
RICININE = inhibits GABA receptors and increases glutamate release, causing seizures
RCA = causes RBC agglutination leading to hemolysis
What are the most common clinical signs seen in lectin toxicity?
- severe watery/bloody diarrhea
- vomiting
- salivation
- abdominal pain
- decreased BP, weakness, trembling, anorexia
- severe reddening, edema and necrosis of GIT mucosa
- decreased nutrient absorption and growth rate
- increased incidence of bacterial infections
- seizures, coma
When should emesis be induced during lectin toxicosis? What treatment is recommended?
animals that vomit
- GI protectants: kaolin-pectin, sucralfate
- fluid and electrolyte therapy
- bland diet
- seizures: Diazepam
What are the 2 major toxic principles of cycad palms? What parts are the most toxic? What species are affected?
- glycosides: cycasin and macrozamin
- β-ethylamino-L-alanine (BMAA)
nuts produced by females (especially Zamiaceae)
cattle, sheep, dogs, cats, horses
What is the mechanism of toxicity of cycad palms?
glycosides are hydrolyzed by β-glycosidases in the GIT into the toxic aglycone, methylazoxy-methanol (MAM) and sugars that are toxic themselves and alkylate DNA and RNA to cause carcinogenesis, mutagenesis, and teratogenesis
What are the effects of the specific toxic principles of cycad palms? What additional effect has an unknown cause?
- cycasin - irritates GIT
- BMAA - neurotoxic by stimulating NMDA receptor leading to excitotoxicity
axonal degeneration in the CNS causes hind limb paralysis in cattle
What are the specific clinical signs of cycad palm toxicity in dogs, sheep, and cattle?
DOGS = (bloody) vomiting, depressing, diarrhea, anorexia, and seizures secondary to hepatic injury
SHEEP = lethargy, anorexia, weight loss, (hemorrhagic) gastroenteritis, death
CATTLE = weight loss, weakness, ataxia, paresis (zamia staggers), hepatic damage
When is decontamination no longer useful with cycad palm toxicity? What 4 treatments are recommended in small animals? What supportive treatment is used?
> 2-4 hours after ingestion
- GI protectants - Sucralfate
- H2 blockers - Cimetidine
- Misoprostol
- hepatoprotectants - acetylcysteine, silymarin, SAMe
IV fluids/electrolytes and blood transfusions for severe GI hemorrhage
What are common sources of acids? What are they referred to as? What molecules do they commonly contain?
toilet cleaners, drain openers, antirust compounds, automobile battery fluid, pool sanitizers
corrosives
HCl, HNO3, H2SO4, H3PO4, C2H2O4, NaHSO3
What are common sources of alkalis? What are they referred to as? What molecules do they commonly contain?
drain openers, oven cleaners, bleaches, industrial cleaners, denture cleaners, bathroom and household cleaners, hair relaxers, alkaline batteries, detergents, cement
caustics
potash, NaOH, KOH, Ca(OH)2, Cac2, NaHCO3
What are the mechanisms of toxicity of acids and alkalis? What happens when they are diluted?
ACIDS - corrosive and cause severe burns on contact with tissue —> coagulative necrosis with resulting scabs limiting penetration
ALKALIS - form hydroxyl ions on contact with water and cause liquefactive necrosis, depending on concentration, pH, viscosity, amount ingested, and duration of contact (more penetrating than acids)
DILUTE = irritants
What are common clinical signs of acid and alkali toxicosis?
- dysphagia
- excessive salivation
- vocalization
- bloody vomiting
- abdominal pain
- PD
- pawing at the mouth
- laryngeal irritation —> laryngospasms, edema —> airway obstruction —> dyspnea, asphyxia
What lesion is associated with acid and alkali toxicosis?
lesions on lipids, tongue, gums, or esophagus
- ACIDS = gray-black
- HNO3 = yellow
What causes renal, CNS, and CVS signs of acid toxicosis? What dermal, respiratory, and ocular signs are observed?
oxalic acid causes systemic binding of calcium, resulting in hypocalcemia
- DERMAL: severe burns, cellulitis, infection, contractures, shock
- RESP: pneumonitis, bronchitis, dyspnea, pleuritic chest pain, pulmonary edema, hypoxemia, bronchospasms
- OCULAR: corneal ulceration, pain, blepharospasms
What specific clinical sign is associated with alkali toxicosis? What ocular and dermal signs are observed?
stridor, vomiting, drooling, and gastric burns due to esophageal ulceration, esophagitis, and stricture formation
- OCULAR: conjunctival irritation and chemosis, corneal defects, perforation, vision loss
- DERMAL: pain, irritation, redness, full thickness burns
What routes of decontamination are recommended for oral, ocular, and dermal exposure to acids and alkalis?
ORAL - milk, water; emesis, gastric lavage, and activated charcoal are contraindicated
OCULAR - irrigate eyes with tepid water or physiologic saline, monitor for ulceration
DERMAL - bathe with water and mild hand dishwashing detergent or non-insecticidal pet shampoo, analgesics, anti-inflammatories, antibiotics
What supportive treatment is recommended for animals with severe upper GI injury in acid/alkali toxicosis? What other supportive therapy is recommended?
strictly NPO —> gastrostomy tube
- IV fluids for hydration, urine output, and BP maintenance
- sucralfate for ulceration
- analgesics: Butorphanol, Buprenorphine, Morphine
- corticosteroid usage for inflammation is controversial
- broad-spectrum antibiotics for mucosal damage, secondary infection, or prophylaxis when corticosteroids are used
What is the most common source of essential oils?
volatile fragrant organic constituents of plants found i fragrances, shampoos, dips, ointments, and oil diffusers
(AVOID using essential oil diffusers with birds in the house)
How are essential oils absorbed? Metabolized? Excreted?
readily absorbed orally and dermally
metabolized in the liver to glucuronide and glycine conjugates
90% urine, 10% feces
What does repeated exposure to essential oils cause? what species are especially affected by toxicity?
induces CYP450 and UDP-glucuronosyltransferase
cats and birds
What clinical signs are associated with oral, respiratory, and dermal exposure to essential oils?
ORAL - vomiting, diarrhea, CNS depression, seizures at high doses
RESP - aspiration pneumonia
DERMAL - ataxia, weakness, muscle tremors, depression, transient parlysis, behavior change, collapse, hypothermia, scrotal dermatitis, liver failure
What is the most common cause of death in essential oil toxicity?
grooming behavior causes concurrent dermal and oral exposure to the oils
What are the charges of metals and non-metals?
metals = cations +
non-metals = anions -
What kind of metal is arsenic? What are the most common sources?
metalloid - properties of metals and non-metals, making it form compounds in which it behaves as cations or anions
- pesticides (ant and roach baits)
- heartworm adulticide - Melarsomine
- feed additives - Na-arsanilate, arsanilic acid, 3-nitro
- environmental: mining/smeling sites, water contamination
What form of arsenic is most toxic? What species is the most sensitive?
trivalent form —> kidneys may reduce a small proportion of an oral dose into this form
cats
How does the form of arsenic affect absorption? Where do they tend to accumulate? What is the major detoxification mechanism? How is it exreted?
pentavalent organic arsenicals are more easily absorbed by the GIT (and intact skin to a smaller extent)
liver, kidney, lungs, GIT
methylation
40-70% urine, bile, and feces
What are the 2 mechanisms of action of trivalent arsenic?
- binds to -SH group in cells, making it able. to inhibit -SH containing enzymes needed for the TCA cycle, decreasing cellular respiration
- damage to vascular system - capillary dilation = transudation of plasma, edema, and shock (GIT most affected)
What is the mechanism of action of pentavalent arsenic? What clinical sign is not seen?
uncouples oxidative phosphorylation leading to a cellular energy deficit
fever
What are the most common clinical signs associated with arsenic poisoning?
- vomiting, salivation
- intense abdominal pain
- watery diarrhea, dehydration
- ruminal or GI atony
- weak pulse, subnormal temp
- renal damage: oliguria, proteinuria, dehydration, acidosis, uremia
What does dermal exposure to arsenic cause? In what animals are nervous signs most common?
- blistering
- edema
- cracking
- bleeding
- secondary infection
swine exposed to organic pentavalent arsenic in feed - ataxia, blindness, dog-sitting, incoordination, paralysis
What are the most common differential diagnoses of arsenic poisoning?
- viral or bacterial gastroenteritis
- pancreatitis
- zinc phosphide
- caustic or irritating agents
- other metals
Why are cathartics no indicated with arsenic toxicity?
poisoning already causes diarrhea
What chelation therapy is preferred for arsenic toxicosis? What else is used?
dimercaptosuccinic acid (DMSA)/succimer
dimercaprol (BAL)
