Heavy Metals Flashcards
Heavy Metals
Metals having an atomic weight greater than sodium (23) and specific gravity (density) greater than 5gm/cm^3
What are the clinical signs of an inorganic heavy metal?
GI signs
Paralysis
What does toxicity depend on with Heavy metals?
Valency
metal to metal interaction
metal to diet interaction
What are the sources of inorganic arsenic toxicosis?
Ant and roach baits Wood preservatives insecticides herbicides fungicides rodenticides milk from poisoned cows are toxic to calves Pastures near smelters
What are the three oxidative states that inorganic arsenic exists in?
Elemental
Trivalent (arsenite)
Pentavalent (arsenate)
What are properties of inorganic arsenic?
Reacts with -SH group
What species is most susceptible to inorganic arsenic toxicosis?
Cattle
Which form is most toxic of inorganic arsenic?
Inorganic trivalent
What is the list of toxicities of inorganic arsenic?
Trivalent is greater than pentavalent is greater than organic arsenic
How are animals exposed to inorganic arsenic?
Absorbed from the GI tract
Intact skin
inhalation
What is the mechanism of action with inorganic arsenic toxicosis?
The trivalent binds to 2-SH groups of lipoic acid which is an essential cofactor for enzymatic decarboxylation of keto acids this slows glycolysis and citric acid cycle
Pentavalent uncouples oxidative phosphorylation and may interfere with vitamins B1 and B6 metabolism
What cells are the most sensitive to inorganic arsenic toxicosis?
Capillary endothelial cells
What tissues are most affected?
Tissues rich in oxidative enzymes: Intestines, liver, kidneys
What are the peracute clinical signs of inorganic arsenic toxicosis?
Sudden death
severe colic
collapse
death
What are the acute clinical signs of inorganic arsenic toxicosis?
severe colic
vomiting
diarrhea - maybe hemorrhagic
What are the subacute clinical signs of inorganic arsenic toxicosis?
diarrhea with blood or mucosal shreds
partial paralysis of hind limbs
detachment of the mucosa causing hypovolemic shock
What are the lesions associated with inorganic arsenic toxicosis?
GI mucosal edema and hemorrhage with sloughing and perforation
capillary degeneration
skin lesions and blistering with skin exposure
What are the best specimens for inorganic arsenic toxicosis?
Liver
Kidney
What is the best antemortem specimen?
urine
What clinical pathology findings are associated with inorganic arsenic toxicosis?
Increased PCV
Increased BUN
High levels in the liver or kidney
What is the symptomatic treatment of inorganic arsenic toxicosis?
Fluids Electrolytes Blood transfusion Treatment of acidosis Vitamins Antibiotics analgesics dopamine acetylcysteine Decontamination: Gastric Lavage, Mineral oil, Activated charcoal, Emetics Demulcents to coat the GI mucosa
What is the chelator of choice for inorganic arsenic toxicosis?
Chelation therapy: Dimercaprol
What are the chelators used for inorganic arsenic toxicosis?
Dimercaprol
Dimercaptosuccinic acid
What is the prognosis for inorganic arsenic toxicosis?
Grave if not treated early
What are the uses of organic arsenicals?
Feed additives to improve weight gain and feed efficiency
control enteric infections in swine and poultry
What organic arsenical is used in swine?
Arsanilic acid
What organic arsenical is used in poultry?
Roxarsone
What are the common sources of organic arsenicals toxicosis?
Overdosage or prolonged use
Recommended concentrations in debilitated dehydrated or sick animals
What are the properties of organic arsenicals?
phenylarsonic acid derivatives
Pentavalent oxidation state
What is important about the toxicity of organic arsenicals?
Organic pentavalent arsenicals are less toxic than inorganic arsenic
What enhances toxicity of organic arsenicals?
dehydration
water deprivation
renal insufficiency
Where are organic arsenicals absorbed from?
GI tract
How are organic arsenicals excreted?
Urine
What is the mechanism of action for organic arsenicals?
Peripheral nerve demyelination and axonal damage
What is the mechanism of action for organic arsenicals similar to?
Vitamin B deficiency
What are the clinical signs of organic arsenicals toxicosis in swine?
incoordination ataxia partial paralysis blindness erythema in white pigs, sensitivity to light
How long for onset of clinical signs of organic arsenicals toxicosis?
3-5 days
What are the clinical signs of organic arsenicals toxicosis in poultry?
Incoordination Ataxia Anorexia Depression Coma Death
What are lesions associated with organic arsenicals toxicosis in swine?
erythemia in light skinned pigs
muscle atrophy in chronic cases
peripheral nerve and optic nerve demyelination and degeneration
gliosis
What is the treatment for organic arsenicals toxicosis?
Withdrawal of organic arsenicals
Supportive therapy: water, fluid therapy, multiple vitamins, antibiotics for bacterial infection
How long can recovery from organic arsenicals take?
2-4 weeks
What is the source of acute copper toxicosis?
Ingestion of high concentrations of copper
What are the clinical signs of acute copper toxicosis?
severe GI signs vomiting colic hemorrhagic diarrhea dehydration shock
What is the treatment for acute copper toxicosis?
Supportive and symptomatic therapy
What is the source of acute copper toxicosis?
Coins
What is the source of chronic copper toxicosis in sheep?
Feed additives
Natural copper in soil and plants
fertilizer
Molybdenum deficiency
How does Molybdenum deficiency cause chronic copper toxicosis in sheep?
Copper levels increase causing a decrease in the ratio of Copper to Molybdenum
What is the normal ratio of Copper to Molybdenum?
6:1
What can cause a sudden loss of copper from the liver to the blood?
Stress
How long does accumulation of copper take in sheep?
2-10 weeks
What is the mechanism of action of chronic copper toxicosis in sheep?
copper accumulation in the liver causes liver degeneration and necrosis
Release of copper from the liver and excess copper in the blood causes oxidation of erythrocyte membranes increasing their fragility resulting in a hemolytic crisis
What does chronic copper toxicosis in sheep cause?
methemoglobin
What are the clinical signs of chronic copper toxicosis in sheep?
weakness anorexia pale mucous membranes icterus hemoglobinuria fever dyspnea shock
What are the lesions associated with chronic copper toxicosis in sheep?
Icterus
hemolysis
methemoglobinemia
Enlarged yellow friable liver
enlarged hemorrhagic bluish dark friable kidneys “gunmetal kidneys”
enlarged dark brown spleen “blackberry jam spleen”
What are the clinical pathology findings for chronic copper toxicosis in sheep?
Elevated serum and whole blood Cu
Elevated liver and kidney Cu
Elevated Liver enzymes (AST, LDH)
What is the treatment for chronic copper toxicosis in sheep?
Ammonium tetrahiomolybate
D-penicillamine
Molybdenized copper phosphate sprayed on pastures
What is the mechanism of action of chronic copper toxicosis in sheep?
Excess free copper causes chronic active hepatitis and liver necrosis due to lipid peroxidation of mitochondrial membranes
What is the source of Molybdenum toxicosis?
Excess Molybdenum
Copper deficiency
What are the properties of Molybdenum toxicosis?
component of xanthine oxidase
elevated molybdenum interferes with copper absorption
Which species is most susceptible to Molybdenum toxicosis?
Cattle
What increased toxicity of Molybdenum?
Dietary sulfate
What decreased toxicity of Molybdenum?
Dietary copper
Where is molybdenum absorbed from?
GI Tract
What is the mechanism of action of Molybdenum toxicosis?
Copper deficiency
Copper is an essential component of enzymes
What are the clinical signs of Molybdenum toxicosis?
Severe diarrhea (greenish with fluids and gas bubbles) Rough hair coat depigmentation of hair especially around the eyes Weight loss anemia osteoporosis exostosis lameness pica Decreased libido and infertility
What is the laboratory findings found with Molybdenum toxicosis?
Elevated Molybdenum
Decreased Copper
Decreased cytochrome oxidase
What is the treatment for Molybdenum toxicosis?
Copper glycinate SC
Copper sulfate added to the diet
What does selenium deficiency cause in lambs, calves, and foals?
White muscle disease
What does selenium deficiency cause in young pigs?
Hepatosis dietetica
What does selenium deficiency cause in chicks?
Exudative diathesis
What does selenium deficiency cause in chickens?
Nutritional pancreatic atrophy
What does selenium deficiency cause in pigs?
Porcine stress syndrome
Which areas have selenium defiecient soil?
NW
NE
SE
Great lakes
What is selenium used in?
Feed supplements
Injectable selenium-vitamin E
Antioxidant supplements
Medicated shampoos for dermatitis
What are the different types of seleniferous plants?
Obligate accumulators
Facultative accumulators
Passive accumulators
What are the obligate selenium accumulators?
Locoweed
Prince’s Plume
Golden Wood
Woody aster
Obligate accumulators
accumulate up to 15,000ppm Se
Require Se for growth
Facultative accumulators
Accumulate up to 25-100ppm
Do not require Se, but they can accumulate it
Passive Accumulators
Accumulate up to 1-25ppm
Accumulate Se passively in Se-rich soil
What plants are passive accumulators?
Crop plants: Corn, wheat, oats, barley, grass, hay
What are the three oxidation states of selenium?
Selenate
Selenite
Selenide
What are some properties of Selenium?
Se combines with -SH group of glutathione
Se is a component of glutathione peroxidase
acts as antioxidant by prevention of peroxide accumulation through reduction of glutathione
Irritant to mucous membranes
What does selenium and vitamin E do for cells?
prevents cell degeneration and cell membrane damage in animals and poultry
How selenium related to thyroid?
Se is found in 5-deiodinase (conversion of T4 to T3)
What is the order of selenium toxicity in plants?
Organic selenium is greater than selenate = selenite which is greater than selenide which is greater than synthetic organoselenium compounds
What promotes the formation of selenate?
Alkaline soil of the Great Plains
What form of selenium is relatively non toxic?
Elemental Selenium
What reduces toxicity of selenium?
high protein diet
ingestion of other elements that bind Se such as Cu
Where is selenium absorbed from?
Small intestine
What form of selenium is more rapidly absorbed?
Organic selenium
What form of selenium is not readily absorbed?
Elemental selenium
Where would you find high concentrations of selenium after chronic exposure?
Hair and Hoof
What increases the biliary excretion of selenium?
Arsenic
What is the mechanism of Action for selenium toxicosis?
Depletion of tissue glutathione
Selenium replaces sulfur in AAs causing abnormal proteins
Decrease ATP in chronic toxicosis
Decreased tissue ascorbic acid
What is the cause of death with acute and subacute selenium toxicosis?
respiratory insufficiency resulting from pulmonary edema hemorrhage
What is the cause of death with chronic selenium toxicosis?
starvation and thirst resulting from weakness, lameness, and blindness
What are the clinical signs of oral acute selenium toxicosis?
GI signs: colic, bloat, dark watery diarrhea
Respiratory signs: fluid in the lungs, bloody froth from the nares, and cyanosis
fever
polyuria
mydriasis
uncertain gait
Death within hours
What are the clinical signs of parenteral selenium toxicosis?
Neurologic signs
Mydriasis
incoordination
What are the clinical signs of subacute selenium toxicosis in cattle?
“blind staggers”
Stage 1: Poor appetitie, aimless wandering, circling, walking through objects
Stage 2: depression, incoordination, foreleg weakness and walking on knees, complete anorexia
Stage 3: Colic, hypothermia,emaciation, clouded corneas near blindness, paresis, coma, and death within hours
What are the clinical signs of selenium toxicosis in swine?
"porcine focal symmetrical poliomyelomalacia" Incoordination lameness paralysis alopecia hoof abnormalities separation of the hoof
What are the clinical signs of chronic selenium toxicosis?
Rough hair coat loss of hair from mane and tail hoof abnormalities sloughing of hooves stiffness in joints lameness partial blindness anemia lethargy emaciation infertility birth defects
What are the Acute lesions associated with selenium toxicosis?
Hemorrhagic gastroenteritis congestion of organs hemorrhages pulmonary edema hydrothorax gut contents may smell like rotten garlic or horseradish
What are the lesions associated with subacute selenium toxicosis in swine?
Focal symmetrical poliomyelomalacia
What lesions are associated with chronic selenium toxicosis?
Abnormal hooves
Cardiac damage
hepatic necrosis
What are the laboratory findings associated with selenium toxicosis?
Elevated selenium
What is the treatment for acute selenium toxicosis?
Saline cathartics
Symptomatic therapy: Oxygen, treatment of pulmonary edema and circulatory shock and gastroenteritis
Acetylcysteine
What is the prevention for selenium toxicosis?
Test soil and forage regularly
Addition of copper to the diet
Increasing sulfur containing proteins in the diet
Addition of organic arsenicals to the diet to increase biliary excretion
What is the prognosis for acute selenium toxicosis?
Poor
What are the highly toxic Heavy Metals?
Pb - Lead
Hg - Mercury
Cd - Cadmium
What are the properties of lead?
Not readily degraded in the environment
Not easily absorbed or metabolized
What happens to lead in the GI tract?
forms insoluble compounds in the GI tract
What type of lead is more readily absorbed?
Organic lead
What conditions favor dissolution an absorption of lead?
Acid conditions
What is the most common source of lead toxicosis in animals?
Lead-based paints
What are the sources of exposure to lead toxicosis?
Paint Old batteries Plumbing Galvanized wire Lead shot lead weight fishing sinkers
What animals are most vulnerable to lead toxicosis from lead shot?
Waterfowl
What absorption of lead is poor?
Dermal
How is lead absorbed?
active transport using the same carrier proteins as calcium
What increased lead toxicity?
Increased GI tract acidity
What important element does Lead displace?
Calcium
What deficiencies increased the absorption of lead?
Calcium deficiency
Vitamine D deficiency
Zinc deficiency
Iron deficiency
Where does lead bind for transport?
RBCs membrane
What is the main route of absorption for lead toxicosis?
GI Tract
What is a liver protein that is involved in cellular detoxification of inorganics and sequesters metal ions present in elevated concentrations?
Metallothionein
Where does lead accumulate?
Active bone matrix
What activates lead stored in the active bone matrix?
Pregnancy
Lactation
Chelating agents
How is lead excreted?
Urine
What ions does lead substitute for?
Calcium
Zinc
Magnesium
Iron
What is the mechanism of action for lead toxicosis?
interferes with biological structure and function
Forms complexes with nucleophilic functional groups
Competes with calcium in the bone and alters calcium movement across membranes
What are the target tissues for lead toxicosis?
GI tract
Blood
CNS
What neurotransmitters does lead interfere with?
GABA
acetylcholine
dopamine
What does chronic exposure to lead lead to?
anemia from inhibited heme synthesis and delayed erythrocyte maturation and fragility
What effect does lead toxicosis have on the brain?
Breakdown of the blood brain barrier and alteration of microvascular systems causing brain edema
What are the GI tract clinical signs of lead toxicosis?
Anorexia salivation vomiting "lead colic" diarrhea constipation rumen atony
What signs do you seen on the erythrocytes with lead toxicosis?
Basophilic stippling
What should we test antemortem for lead toxicosis?
Whole Blood concentration
What should we test post mortem for lead toxicosis?
Kidney and liver
What are the CNS clinical signs seen with lead toxicosis?
Anxiety hyperexcitability vocalization head pressing circling running maniacal behavior tremors blindness
What Clinical signs can you see in a horse with acute lead toxicosis?
Pharyngeal paralysis
“Roaring”
seizure like activity
What are the clinical pathology findings associated with lead toxicosis?
Increased nucleated RBCs
Non-regenerative anemia
Basophilic stippling
Fluorescence of porphyrins in plasma or urine
What do you find on urinanalysis with lead toxicosis?
Increased delta-animolevulinic acid dehydrase levels
What is the treatment for lead toxicosis?
Stabilize the patient: Fluids/electrolytes
Eliminate the Lead if possible
NO ACTIVATED CHARCOAL!
Chelating agent
Which chelating agents is used to treat lead toxicosis?
Calcium disodium EDTA
Dimercaptosuccinic acid
Dimercaprol
D-penicillamine
What do you use to treat the neurologic signs of lead toxicosis?
Mannitol
Diazepam
What are some adjunct therapies that can be used to treat lead toxicosis?
Taurine
Thiamine
Zinc supplementation
What is the prognosis for lead toxicosis?
Good with mild to moderate clinical signs and treated prompty
Guarded to poor in animals showing severe CNS signs
Ingesting some forms of Zinc can cause the creation of what?
toxic zinc salts
What is zinc important for?
Growth cell proliferation skeletal development collagen formation skin feathering wound healing reproduction immune system function direct stabilizing effect on cellular membranes Function of taste and smell receptors Component of many enzymes
Where is zinc widely found in the environment?
EVERYWHERE! Air Water Foodstuffs Living organisms
How are animals exposed to zinc toxicosis
Ingestion of pennies Galvanized metals batteries jewelry skin ointments lotions shampoos wound healing agents overdose of zinc dietary supplement
What increases zinc release and absorption?
Acid environment
What decreased zinc absorption?
Dietary fiber
Phytate
Phosphorus
Calcium
Where is the most rapid accumulation of zinc?
Pancreas Liver Kidneys Spleen Male reproductive organs
What is the mechanism of action of zinc toxicosis?
Unknown
Intravascular hemolysis
What are the two ways zinc toxicosis affects the body?
Intravascular hemolysis
Renal injury
How does zinc affect the RBCs?
Direct damage of the RBCs membrane
damage to red blood cell organelles
Immune mediated destruction from hapten formation
inhibition of specific red blood cell biochemical mechanisms
What are the GI tract clinical signs of zinc toxicosis?
vomiting anorexia lethargy abdominal pain diarrhea pica
What are the Hematologic clinical signs of zinc toxicosis?
Hemolytic anemia
icterus
hemoglobinuria
What are the renal clinical signs of zinc toxicosis?
Azotemia
hyperphosphatemia
What are the lesions associated with zinc toxicosis?
Gastritis Gastric ulcers renal tubular casts liver damage pancreatitis
What are the laboratory findings associated with zinc toxicosis?
Hemolytic anemia icterus hemoglobinuria azotemia hyperphosphatemia pancreatitis?
What is the treatment for zinc toxicosis?
Decontamination: remove the object, Cathartics
Supportive care: Blood transfusion, oxygen, fluids, treatment of renal failure or pancreatitis
What is wrong with using chelating agents with zinc toxicosis?
May increase zinc absorption and cause further damage to the kidneys
What is the prognosis for zinc toxicosis?
Good with early diagnosis
Guarded to poor with severe hemolytic crisis
What is ferric stored as?
Hemosiderin
Ferritin
Transferrin
Which form of iron is used in enzymes?
Ferric
What is the source of exposure to iron toxicosis?
Oral supplements fertilizers slug/snail bait Hand warming pads Iron products parenteral iron preparations
What are the forms of injectable iron used?
Iron dextran
Iron dextrin
iron sorbitol
ferric ammonium citrate
What are the forms of iron?
Elemental
divalent
trivalent
What inreases the risk of iron toxicity in piglets?
Selenium and Vitamin E deficiency in sows
Which form of iron is less irritant?
Organic iron
Ferrous
What is different about iron excretion?
Animals lack a mechanism to excrete iron
How does acute iron toxicosis cause free iron?
Acute iron toxicosis overwhelms the selective absorption mechanism and saturates ferritin in the GI mucosal cells leading to absorption of toxic concetrations of free iron
What is the mechanism of Action for iron toxicosis?
Free iron ions are very reactive and cause free radical lipid peroxidation and direct damage to the membranes
Circulating iron accumulates int he liver causing mitochondrial damage and liver damage and systemic acidosis
What can excessive free iron cause?
fatty necrosis of myocardium
post arteriolar dilation
increased capillary permeability
reduced cardiac output
What are the acute clinical signs of iron toxicosis?
Severe depression
shock
acidosis
death within hours
What are the stages of acute iron toxicosis?
Stage 1: Nausea, vomiting, diarrhea, GI hemorrhage
Stage 2: apparent recovery, GI signs resolve, animal becomes more alert
Stage 3: Vomiting, diarrhea, metabolic acidosis, coagulation disorders, heaptic failure, CV collapse
Stage 4: GIT obstruction secondary to fibrosisng of damaged GI tract
What are the lesions associated with iron toxicosis?
Yellowish brown discoloration at injection sites and lymph nodes GIT ulceration hemorrhagic enteritis Congestion of liver and kidney liver necrosis icterus hemoglobinuria
What are the laboratory findings associated with iron toxicosis?
Elevated serum iron
Increased saturation of the serum Total Iron-Binding capacity
Acidosis
Hemoglobinuria
What is the treatment for iron toxicosis?
GI tract decontamination: Emesis, gastric lavage, Milk of Magnesia to precipitate iron
Supportive treatment: IV fluids, GI protectants, treatment of anaphylactoid reactions
What are the chelating agents used for iron toxicosis?
Deferoxamine
What is the prognosis for iron toxicosis?
Good if treated early
Guarded to poor in animals with severe clinical signs
