Gastrointestinal Toxicology, Pt. 2

Question 1

What is essential mineral are baby pigs born deficient in?

Answer 1

iron —> typically supplemented with an injection

Question 2

What is the most common cause of iron toxicosis? What is a hereditary cause in humans? In what animals is toxicosis most common?

Answer 2

overdosing or ingestion of iron-containing products

hereditary hemochromatosis - mutation of high iron (HFE) gene causing excessive intestinal absorption and storage of iron leading to overload

dogs

Question 3

What are the most common exposures to iron in dogs and cattle/horses/pigs?

Answer 3

DOGS = accidental ingestion of iron-containing vitamins, supplements, molluscicides (phosphate, EDTA), fertilizer, oxygen-absorbing sachets or hand-warming pads

CATTLE/HORSES/PIGS = administration of excess amounts of iron supplements or fertilizer

Question 4

Where is iron absorbed? In what form is it absorbed best? How does it circulate in blood?

Answer 4

small intestine, massive overdose results in absorption in all parts of the GIT

Fe2+, by divalent metal transporter (DMT1)

bound to transferring

Question 5

Where is iron found in the body? How is it excreted?

Answer 5

• 70% in hemoglobin
• 5-10% in myoglobin
• rest in storage as ferritin and enzymes

exfoliation of intestinal epithelium (in small amounts)

Question 6

What 4 mechanisms of toxicity does iron have on the GIT?

Answer 6

1. direct corrosive effect
2. redox recycling between Fe2+ and Fe3+ causes the production of ROS and oxidative damage to cells and organelles (membrane lipid peroxidation)
3. stimulate serotonin and histamine release
4. causes metabolic acidosis by causing hypovolemia, hypotension, anaerobic metabolism, interference with mitochondrial ETC

Question 7

What 4 effects does iron toxicosis have on the cardiovascular system?

Answer 7

1. fatty necrosis of myocardium
2. vasodilation
3. increased capillary permeability
4. decreased cardiac output

Question 8

How does iron toxicosis affect the clotting cascade?

Answer 8

inhibits the formation of fibrin from fibrinogen

Question 9

What are the 5 major systems affected by iron toxicosis? What clinical signs are associated with each?

Answer 9

1. GI - vomiting/hematemesis, melena, diarrhea, ulceration, abdominal pain
2. CVS - hypotension, hypovolemia, increased capillary permeability, shock, cardiomyopathy due to fat necrosis
3. HEPATIC - hypoglycemia, hyperammonemia, hepatic encephalopathy
4. CNS - depression, cerebral edema, seizures, tremors, coma
5. BLOOD - coagulation defects

Question 10

What does peracute iron toxicity in pigs resemble?

Answer 10

anaphylactic shock

Question 11

What are the 4 stages of iron toxicosis? What clincal signs occur at each?

Answer 11

• STAGE I: 0-6 hr; GI effects and depression
• STAGE II: 6-12 hr; latent period with apparent clinical recovery
• STAGE III:12-96 hr; acidosis, GI, hepatic, CVS, CNS
• STAGE IV: 2-6 weeks; GIT ulcers heal with scar tissue formation causing stricture development and GI obstruction

Question 12

How is iron toxicosis diagnosed? What are some differential diagnoses?

Answer 12

• measurement of serum iron levels within 4-6 hours of ingestion
• measurement of serum iron binding capacity
• radiography may show a mass of iron tablet (bezoar) or foreign body in the GIT

garbage toxicosis, gastric torsion, ingestion of caustic/corrosive agents, snake bites, bacterial or viral enteritis

Question 13

How is gastric decontamination done in iron toxicosis? What is avoided?

Answer 13

• give eggs, water, or milk and induce emesis for recent exposure
• perform gastric lavage
• surgical removal is radiography reveals iron tablet bezoar followed by aggressive gastric lavage

activated charcoal

Question 14

What is used to treat iron toxicosis? What adverse effect does it have?

Answer 14

chelation therapy with deferoxamine (Desferal)

causes reddish-brown discoloration of urine

Question 15

What supportive treatment is recommended for iron toxicosis? What is recommended for anaphylactic shock in pigs?

Answer 15

• restore fluids, electrolytes, and acid-base status
• GI protectants: sucralfate, cimetidine, misoprostol, gastric acid secretion inhibitors

antihistamines, epinephrine, oxygen, IV fluids

Question 16

What rodenticide affects the GIT?

Answer 16

metallophosphide rodenticides (zinc phosphide) extensively used around farms and barns to protect grain

• Rattoff
• ZP Tracking Powder
• Eraze
• Sweeney’s Poison Peanuts

Question 17

What happens following zinc phosphine ingestion?

Answer 17

• ZP ins hydrolyzed in the acidic pH in the stomach into toxic phosphine gas
• gas is readily absorbed by passive diffusion
• any intact ZP is also absorbed in the GIT

Question 18

How is zinc phosphine excreted?

Answer 18

• intact and gas ZP = lungs
• phosphorus oxide, phosphite, hypophosphite metabolites = renal

Question 19

What is the GIT mechanism of toxicity of zinc phosphine? What are 4 systematic effects?

Answer 19

ZP = corrosive action leading to acute hemorrhagic emetic effect on GIT

1. phosphine gas impairs oxidative phosphorylation by inhibiting cytochrome c oxidase
2. phosphine gas induces ROS formation leading to oxidative damage to lipids, proteins, DNA, and cell death
3. phosphine gas denatures hemoglobin causing methemoglobinemia
4. phosphine gas causes cellular hypoxia

Question 20

What can increase toxicity of zinc phosphine? Decrease?

Answer 20

food in stomach increases HCl and phosphine gas production (onset is rapid with a full stomach)

ZP induces vomiting, which decreases phosphine has production

Question 21

What does zinc phosphine toxicity resemble? What is seen in dogs?

Answer 21

strychnine or fluoroacetate

• depression, agitation, apprehension
• dyspnea, pacing, ataxia, weakness, anorexia
• bloody vomiting, salivation
• tremors, convulsions, howling, aimless running
• teeth barring or grinding

Question 22

What clinical signs are observed in zinc phosphine toxicity in ruminants and horses?

Answer 22

RUMINANTS = abdominal pain, bloating

HORSES = colic

Question 23

What unique clinical signs is caused by zinc phosphine toxicosis? What causes death?

Answer 23

acetylene (garlicky/rotten fish) odor in the breath, vomitus, and stomach contents

respiratory arrest

Question 24

How are stomach contents or vomitus analyzed for zinc phosphine?

Answer 24

• samples are packed in airtight containers and freezed to prevent phosphine gas loss
• PREFERABLE: freeze entire carcass, vomitus, and suspected bait and send to diagnostic lab

Question 25

What rapid screening tool is used to diagnose zinc phosphine toxicity?

Answer 25

silver nitrate paper - diluted gastric content heated in a flask up to 50 C for 1-5 minutes keeping the paper on the mouth of the flask - if it turns black, phosphine is present due to the formation of silver phosphate

Question 26

What is recommended to cause emesis in the case of zinc phosphine toxicity? What is recommended for animals that do not vomit? What treatment is able to slow the hydrolysis of ZP into its gas form?

Answer 26

centrally acting emetics - Apomorphine, Xylazine, activated charcoal activated charcoal mixed with antacid (aluminum or magnesium hydroxide) oral aluminum or magnesium hydroxide antacid

Question 27

What treatments are recommended for acidosis, respiratory difficulties, and shock associated with zinc phosphine toxicosis?

Answer 27

increase pH with liquid antacid gels containing Mg(OH)2, Al(OH)3, and CaCO3 oxygen administration and assisted breathing corticosteroids

Question 28

What 5 treatments are recommended for liver failure associated with zinc phosphine toxicosis?

Answer 28

1. sodium thiosulfate 2. lipotropic agents 3. B vitamins 4. dextrose 5. low protein diets

Question 29

How are seizures, excessive muscle activity, GI ulcers, muscarinic signs, and gastric distension associated with zinc phosphine toxicosis?

Answer 29

Propofol, Barbiturates, gas anesthetics Methocarbamol GI protectants - Sucralfate, H2 blockers, PPIs Atropine nasogastric or orogastric tubes

Question 30

What is cantharidin?

Answer 30

bicyclic terpenoid vesicant found in the hemolymph and genitalia of male blister beetles (Epicauta spp.) and is able to be transferred to females during copulation - aphrodisiac (Spanish Fly) - diuretic - abortifacient - wart medications

Question 31

What is cantharidin toxicosis associated with?

Answer 31

eating alfalfa hay in semiarid areas, like TX and OK - cutting and crimping increases chances of incorporating beetles in the hay (beetles are gregarious and tend to swarm)

Question 32

What is the most toxic blister beetle?

Answer 32

Striped blister beetle

Question 33

What is the mechanism of action of cantharidin? In what 4 ways does it cause this?

Answer 33

irritation of the GIT leads to acantholysis and vesicle formation with ulcers and erosions 1. promotes mitosis in epithelial cells 2. interferes with oxidative enzyme systems in the mitochondria causing permeability changes 3. disrupts cell membranes 4. inhibits protein phosphatase 2A, which modulates phosphatases and protein kinases leading to alterations of cellular processes including proliferation, apoptosis, and membrane channels/receptors activity

Question 34

What species are most susceptible to cantharidin toxicosis? How does dosage affect clinical signs?

Answer 34

horses*, cattle, sheep, goats, dogs, rabbits, alpacas, emus - MASSIVE = shock and death within 4 hr - SMALLER = gastroenteritis, nephrosis, cystitis, urethritis

Question 35

What clinical signs are associated with cantharidin toxicosis in horses?

Answer 35

- submerging muzzles without drinking, playing in the water - colic, diarrhea, ulceration of oral mucous membranes, salivation - anorexia, mucoid or bloody feces - dysuria, hematuria

Question 36

What general clinical signs are associated with cantharidin toxicosis?

Answer 36

- restlessness, depression, weakness - collapse, prostration - dehydration, sweating - fever, muscle rigidity and fasciculations, stiff gait - myocarditis causes CVS signs - dyspnea with rales due to pulmonary edema - mortality in ~50% of horses

Question 37

What are 4 major clinical pathology signs associated with cantharidin toxicosis?

Answer 37

1. hypocalcemia and hypomagnesemia 2. elevated BUN 3. increased PCV and protein due to dehydration and shock 4. reduced USG

Question 38

What are the 6 major lesions associated with cantharidin toxicosis?

Answer 38

1. erosion and ulceration of the oral cavity and GIT 2. acantholysis or epithelium of the urinary tract and renal tubular nephrosis 3. renal cortical hemorrhage 4. urethra and bladder mucosa hemorrhage 5. ventricular myocarditis 6. pulmonary edema

Question 39

What can be used to enhance urinary and fecal elimination of cantharidin? How are hypocalcemia and hypomagnesemia treated? Pain?

Answer 39

mineral oil hastens movement through GIT and activated charcoal binds to it supplement IV fluids with Ca and Mg, but no bicarb α-adrenergic agonists (common analgesics may not provide adequate relief)

Question 40

What are the 3 major causes of garbage toxicosis? When is toxicosis especially common?

Answer 40

1. waste food or dead animals contaminated with bacteria and/or toxins 2. feeding animals food considered unfit for human consumption 3. high moisture dog food left at warm temperatures warm seasons/regions with poor hygiene and roaming animals

Question 41

What 4 bacteria commonly cause garbage toxicosis? What are the 2 mechanisms of toxicity?

Answer 41

Streptococcus, Salmonella, Clostridium, Bacillus 1. sorption to and irritation of GI epithelium causes vomiting 2. increases the permeability of GI epithelial cells, leaking fluid and electrolytes into the lumen which interferes with absorptive mechanisms

Question 42

What endotoxin causes garbage toxicosis? What results from toxicity?

Answer 42

LPS produced by Gram-negative bacterial released upon bacterial cell lysis AFFECTS THE WHOLE BODY - circulatory shock, DIC, acute respiratory distress syndrome, systemic inflammatory response syndrome, multiple organ dysfunction syndrome, collapse, death

Question 43

What are 8 mechanisms of toxicity caused by endotoxins causing garbage toxicosis?

Answer 43

1. activation of inflammatory mediators 2. cardiovascular insult 3. alteration of GIT permeability 4. interference with gut function including endocrine regulation of gastric emptying 5. activates pancreatic zymogens 6. competes with insulin for the same receptor 7. activates complement and clotting cascades 8. uncouples oxidative phosphorylation

Question 44

What are the clinical signs associated with enterotoxicosis caused by garbage toxicosis?

Answer 44

vomiting and retching - bloody diarrhea - abdominal pain, stasis and dilation of gut (gas accumulation) - dehydration, electrolyte imbalance

Question 45

What are the clinical signs associated with enterotoxemia caused by garbage toxicosis? What are signs of endotoxic shock?

Answer 45

- fever, shivering - vomiting, abdominal pain, tenderness, and distension - muddy mucous membrane - watery/bloody diarrhea - EXCEEDINGLY foul-smelling feces depression, collapse, hypotension, hypo/hyperthermia

Question 46

What must be ruled out when diagnosing garbage toxicosis?

Answer 46

- foreign body and intestinal displacement (volvulus, torsion, intussusception) - pancreatitis - acute hepatic and renal failure

Question 47

What 5 supportive and systematic treatments for garbage toxicosis is suggested?

Answer 47

1. fluid and electrolyte therapy with bicarbonate 2. Heparin for DIC 3. Corticosteroids for shock 4. IV Chloramphenicol to control bacterial proliferation 5. bland diet