Tox Exam 2 Metals and Minerals Flashcards
What species are resistant to copper toxicity?
swine and poultry
Acute copper toxicosis causes what clinical signs?
V+, colic, bloody D+, dehydration, shock
Tx of acute copper toxicosis?
supportive, symptomatic
T/F Acute copper toxicosis is more common than chronic copper toxicosis.
FALSE
Causes of chronic copper toxicosis?
excess copper, molybdenum deficiency, or BOTH
also unavailability of sulfate
Normal copper:molybdenum ratio?
6:1
Accumulation of copper requires about ______ weeks exposure in sheep.
2-10 weeks
Cause of secondary copper toxicosis?
liver damage may cause copper accumulation by hepatocytes
What causes a sudden loss of copper from liver to blood?
stress
MOA in chronic copper toxicosis?
Cu accumulation in liver causes liver degeneration and necrosis. Release of Cu from liver and excess Cu in blood causes oxidation of erythrocyte membranes, increasing their fragility–hemolytic crisis! Also Cu in blood causes oxidation of hemoglobin to methemoglobin.
T/F Methemoglobin is unable to efficiently carry oxygen.
TRUE
Which organ is responsible for removing excess copper from blood?
liver
Main mechanism that Cu is removed from the body?
bile
Main mechanism that copper molybdate (CuMoO4) is removed from the body?
urine
Clinical signs of chronic copper toxicosis?
sudden onset of weakness, anorexia, pale MM, icterus, hemoglobinuria, fever, dyspnea, shock.
Characteristic lesions of liver due to chronic copper toxicosis?
enlarged, yellow, friable
Characteristic lesions of kidneys due to chronic copper toxicosis?
enlarged, hemorrhagic, bluish-black, friable–“gun metal kidneys”
Characteristic lesions of spleen due to chronic copper toxicosis?
enlarged, dark brown to black—“blackberry jam spleen”
Preferred specimens for chronic copper toxicosis?
blood or serum
elevated Cu, liver enzymes AST, LDH (3-6 wks prior to hemolytic crisis)
Differential diagnosis for chronic copper toxicosis?
hemolytic agents—zinc, naphthalene, DMSO, guaifenesin
poisonous plants—onion, gossypol (cottonseed), red maple (equine only)
infectious dz—lepto, babesia, anaplasma, bacillary hemoglobinuria
certain snake venoms
Treatment for chronic copper toxicosis?
Ammonium tetrathiomolybate or D-penicillamine
Dog breed susceptibilities for chronic copper toxicosis?
mainly Bedlington terrier (autosomal recessive) @ 2-6 yrs, West Highlands, Skye terriers, Dobermans
Prevention of chronic copper toxicosis?
molybdenized copper phosphate sprayed on pastures, supplemental zinc reduces hepatic Cu accumulation, add molybdate to sheep rations, ammonium molybdate and thiosulfate orally daily for individual sheep
States where soil is rich in molybdenum?
Florida, California, Oregon and Nevada
T/F plants accumulate molybdenum from soil
TRUE
T/F Molybdenum deficiency causes copper deficiency.
FALSE. EXCESS molybdenum causes copper deficiency. Elevated molybdenum interferes with copper absorption.
Sources of molybdenum?
plants, soil, industrial contamination–brick plants and steel mills, molybdenum containing fertilizers
T/F Copper deficiency causes molybdenum toxicosis.
TRUE. also copper deficiency can lead to anemia, loss of pigmentation, demyelination, etc.
What species is the most susceptible to molybdenum toxicosis?
cattle. toxicosis also seen in sheep.
What species are resistant to molybdenum toxicosis?
horses and pigs
High levels of dietary _____ increase molybdenum toxicity.
sulfate
High levels of dietary _____ decrease molybdenum toxicity.
copper
Excretion of molybdenum?
in milk in toxic levels
Clinical signs of molybdenum toxicosis?
severe D+ (greenish w/ gas bubbles)–NOT hemorrhagic 8-10 days following exposure, rough hair coat and depigmentation of hair, loss of weight, anemia, osteoporosis, lameness, pica, decreased libido in bulls and infertility in cows
Main location of depigmentation of hair in molybdenum toxicosis?
around the eyes
Best specimen for dx of molybdenum toxicity?
blood. elevated molybdenum, decreased copper, decreased cytochrome oxidase activity.
Differential diagnosis for molybdenum toxicity?
selenium toxicity
Treatment of molybdenum toxicity?
copper glycinate SC or copper sulfate added to diet
MOA of copper deficiency due to molybdenum toxicity?
Cu involved in hematopoeisis, CT metabolism, myelin formation in newborns, pigmentation and bone formation. Cu is a component in essential enzymes such as cytochrome oxidase and aromatic amino acid metabolizing enzymes—tyrosinase, dopamine hydroxylase, MAO. Cu containing proteins (cupreins) in most aerobic cells have superoxide dismutase activity.
Other names for selenium deficiency disease?
White muscle disease (WMD) or nutritional muscle dystrophy (NMD) in lambs, calves and foals. Hepatosis dietetica in young pigs, porcine stress syndrome in pigs, exudative diathesis in chicks, nutritional pancreatic atrophy in chickens!
Regions with soil deficient in selenium?
northwest, northeast, southeast, great lakes, st kitts
States with soil rich in selenium?
N. and S. Dakota, Wyoming, Montana, Nebraska, Kansas, Utah, Colorado, New Mexico
Selenium uses?
Feed supplements for cattle, sheep, swine, poultry. Injectable selenium-vit E preparations. Used in medicated shampoos for treatment of dermatitis. Antioxidant supplements for animals and humans.
Selenium sources?
graze seleniferous plants—cattle, sheep, horse
eat grains grown on Se-rich soils–pigs, poultry
Se contaminated water—waterfowl
improper use of Se shampoos (SA) or supplements/preparations
T/F Selenium contaminated water is carcinogenic in waterfowl.
FALSE—teratogenic
What are the 3 oxidation states of selenium?
selenate (+6), selenite (4+), selenide (-2)
Name 2 elements that are irritants to mucous membranes.
selenium and arsenic… many more!
T/F Selenium toxicity is increased by a high protein diet and Cu.
FALSE. toxicity is decreased!
Ranking of the different selenium states’ toxicities.
organic Se in plants > selenate = selenite > selenide > synthetic organoselenium compounds
T/F Seleniferous plants have a bad odor and are unpalatable–only eaten when other forage is unavailable.
TRUE!
ADME of selenium?
A=readily from SI, soluble organic plant Se more easily abs than selenite, selenate, selenide–elemental Se not absorbed bc insoluble in water
D=throughout body–particularly to liver, kidney, spleen–crosses placenta!
E=in milk, mainly in urine, also bile
Chronic exposure of selenium increased concentrations in _____.
hoof and hair
T/F Selenium crosses placenta but has no negative effects on the fetus.
FALSE–teratogenic!!
What element increases biliary excretion of selenium?
arsenic!
Chemical properties of selenium?
Se combines with SH group of glutathione and is a component of glutathione peroxidase. it acts as an antioxidant by prevention of peroxide accumulation through reduction of glutathione. Vit E is synergistic to glutathione peroxidase—Sel/vit E deficiency prevents cellular membrane and cell degeneration in animals.
Se also found in 5-deiodinase (converts T4-T3)
MOA of selenium toxicosis?
irritate GI mucosa, dramatic decrease in tissue glutathione and tissue ascorbic acid, decreased ATP.
Se replaces sulfur in amino acids causing abnormal proteins.
What are the forms of selenium toxicosis?
acute, subacute, chronic
Clinical signs of acute selenium toxicosis?
oral–>
GI: colic, bloat, dark watery D+
Resp: labored resp w/ fluid sounds in lungs, bloody from nares, cyanosis
Other: fever polyuria, mydriasis, uncertain gait
parenteral–>neuro signs including mydriasis and incoordination
death=d/t resp insufficiency from pulmonary edema/hemorrhage
Clinical signs of subacute selenium toxicosis?
cattle–>”blind staggers”
stage 1: poor appetite, aimless wandering, circling, walking into objects, normal resp and temp
stage 2: stage 1 signs + depression, incoordination, foreleg weakness, walking on knees, anorexia
stage 3: colic, hypothermia, emaciation, clouded corneas near blindness, paresis, coma, death in hrs
sheep–> similar to cattle but stages not well defined
swine–>”porcine focal symmetrical poliomyelomalacia”, incoordiation, lameness, paralysis, alopecia, hoof abnormalities, separation of hoof
death=d/t resp insufficiency from pulmonary edema/hemorrhage
Clinical signs of chronic selenium toxicosis?
rough hair coat, loss of hair from mane and tail, hoof deformaties and sloughing, stiffness of joints, lameness, partial blindness, anemia, lethargy, emaciation, infertility, birth defects
death= d/t starvation or thirst from weakness, lameness, blindness
Pathology of acute selenium toxicosis?
hemorrhagic gastroenteritis, congestion of organs, hemorrhages, pulmonary edema, hydrothorax
gut contents may smell like rotten garlic/horseradish (hydrogen selenide)
Pathology of subacute selenium toxicosis?
swine–focal symmetrical poliomyelomalacia
Pathology of chronic selenium toxicosis?
abnormal hooves, cardiac damage, hepatic necrosis
Treatment of acute selenium toxicosis?
saline cathartics
symptomatic–> O2, tx pulmonary edema, circulatory shock, gastroenteritis
acetylcysteine
Prognosis of selenium toxicosis?
poor in acute toxicosis bc animals die quickly
Prevention of selenium toxicosis?
soil/forage should be tested regularly for Se levels, remove animals from seleniferous areas, adding Cu to diet, high protein diet, increased sulfur containing proteins may reduce tox, addition of organic arsenicals to diet to increase biliary excretion
Diagnosis of selenium toxicosis?
specimens–>blood, kidney, liver in acute; hair, hoof in chronic
blood–>increased Se, blood/plasma glutathione peroxidase activity correlates w/ blood Se concentrations in cattle, sheep, swine but NOT HORSES!!
Differential diagnosis of selenium toxicosis?
acute, subacute–>pneumonia, infectious hepatitis, enterotoxemia, pasteurellosis
chronic–>molybdenum tox, fluoride tox, freezing, ergotism, laminitis
Is lead degraded in the environment?
NOT degraded in environment, also NOT easily metabolized
______ conditions favor dissolution of lead.
acidic
What percentage of iron is absorbed from the GIT?
only 1-2% bc it forms insoluble compounds
What species are most susceptible to lead poisoning?
cattle, horses, pets, waterfowl, wild birds
What species are more resistant to lead poisoning?
goats, swine, chickens
______ are more frequently poisoned d/t indiscriminate eating habits.
puppies
more sensitive than adults d/t increased abs and crosses BBB more readily
ADME of lead?
A=oral abs poor, using same carrier protein as calcium
D=98-99% bound to RBCs, throughout body, crosses BBB and placenta
E=slowly mainly in urine, small amount bile, in milk at toxic levels
T/F Absorption of lead is increased by an acidic environment.
TRUE
Absorption is greater in adults or young?
young
What factors decrease absorption of lead?
calcium, zinc, protein
Deficiency in these factors increases the absorption of lead.
calcium, zinc, iron, vit D
Sources of lead toxicosis?
most common source is lead-based paints (before 1977), paint, batteries, plumbing solder, putty, galvanized wire, lead shots, lead weights, fishing sinkers, leaded materials in refuse piles, linoleum, imported ceramics and pottery, contaminated pastures from industry
Clinical signs of lead toxicosis?
GI–>anorexia, +/- salivation, V+, lead colic, D+ or constipation, rumen atony, rare megaesophagus in SA
CNS–>anxiety, hyper excitability, vocalize, head pressing, circling, running, maniacal behavior, seizures, tremors, blindness, pharyngeal paralysis, roaring (horses), CNS depression in horses/sheep
Hematologic–>signs related to anemia
Onset of clinical signs of lead toxicosis?
few hours, days, wks, months to develop–depends on ant, species, plus other factors
What form of lead toxicosis is most common?
subacute
Pathology of lead toxicosis?
cerebral cortical necrosis and poliomalacia in cattle. acid-fast eosinophilic intranuclear inclusion bodies in renal tubular epithelium or hepatocytes.
grossly–may see lead in GIT
Antemortem specimen of choice in lead toxicosis?
whole blood
other specimens include liver, kidney, GI contents
Hematology in lead toxicosis?
increased nucleated RBCs, basophilic stippling in dogs, increased zinc protoporphyrin esp in dogs, increased blood lead concentration
note: fluoresence of plasma porphyrins under UV light in cattle
What can be detected in radiographs of animals with lead toxicosis?
lead objects in GIT, metaphyseal sclerosis in young animals in chronic tox
Urinalysis in lead toxicosis?
increased delta-ALA-D levels, increased urinary lead following EDTA admin
Differential diagnosis of lead toxicosis?
chlorinated hydrocarbons, urea, OP, carbamates, H2O deprivation/sodium tox, metaldehyde, strychnine, fluoroacetate, nicotine, mercury, PEM in cattle, lupinosis in sheep, hypovitA, hypoMg, bovine ketosis
Treatment of lead toxicosis?
decon–>magnesium sulfate (osmotic cathartic), sx removal of lead
supportive/symptomatic–>thiamine, glucocorticoids, mannitol, zinc supplements, diazepam, barbiturates, fluid therapy
chelation–on later card
List the chelation drugs used to treat lead toxicosis?
calcium disodium EDTA, dimercaprol (given before EDTA), D-penicillamine PO (given after EDTA), Dimercaptosuccinic acid (DMSA, succimer)
Prognosis of lead toxicosis?
guarded–better if caught early
What is the chelation drug of choice in lead toxicosis?
calcium disodium EDTA
What are the negative side effects of calcium disodium EDTA?
anorexia, V+, D+, depression.
prolonged therapy may cause kidney damage. may increase signs of toxicosis d/t mobilization of lead from bone and soft tissues. side effects can be antagonized by zinc supplementation.
Chelation drug of choice in pet birds suffering from lead toxicosis?
Dimercaptosuccinic acid (DMSA, succimer)
Why is dimercaprol given before administration of calcium disodium EDTA in lead toxicosis?
may improve effect bc crosses BBB and enhances renal and biliary excretion of lead
