4.4 Metals and Environmental Toxicants Flashcards
hard metals follow what kind of curve
dose-response (i.e. too deficient or too much leads to toxicity)
give an example for the following functions of metals in the body:
- cofactors for many enzymes, ex. kinases
- oxygen transport
- antioxidants
- bone formation
- endocrine
- muscle contraction
- immune function
- cofactors for many enzymes, ex. kinases -> Mg
- oxygen transport -> heme Fe
- antioxidants -> Se containing glutathione
- bone formation -> Ca, P
- endocrine -> iodine for thyroid hormone
- muscle contraction -> Ca
- immune function -> Zn
what are some sources of lead
old paint, leaded gasoline, plumbing pipes, ammunition, fish sinkers, construction materials, stained glass, toys
what are the 3 forms of lead and some examples
1) metallic aka elemental lead: batteries, weight to balance tires
2) inorganic lead: old paints
3) organic lead: gasoline additives
what is the difference between elemental, inorganic and organic lead
elemental/metallic: pure Pb
inorganic: bound to other elements
organic: bound to carbonated groups (methyl, ethyl)
what are the signs of ACUTE lead toxicosis
gastropathy, lethargy, anorexia, anemia, encephalopathy, neuropathy
what are the signs of CHRONIC lead toxicosis
weight loss, impaired bone growth, peripheral neuropathy, impaired brain development in children
lead toxicosis MOA involves conversion of ___________ to ___________
δ-aminolevulinic acid -> protoporphyrin
what does lead do to RBCs
inhibits maturation by binding to RBCs -> rubricytosis and basophilic stippling observed on blood smear
rubricytosis in the absence of a regenerative response is indicative of what toxicity
lead
acute lead toxicity is associated with what neurologic condition
polioencephalomalacia
lead poisoning in waterfowl and raptors is associated with what? what are the clinical signs
peripheral neuropathy:
- demyelination of Schwann cells
- peripheral motor nerve dysfunction
muscle wasting, muscle weakness, inability to feed
how do we diagnose lead toxicity (4)
- history of exposure
- clinical signs
- x-rays
- hematology (rubricytosis, basophilic stippling, anemia)
lead is 90% bound to
RBCs
what species absorbs copper from the diet very efficiently but excrete it slowly
sheep
where does copper accumulate/store (3)
liver, kidney, brain
T/F copper binds to blood proteins
T
Cu bioavailability is reduced by interactions with ____ and ____
Mo and S
Cu toxicity causes what injuries (4)
- liver injury/inflammation/fibrosis
- oxidative stress on RBCs -> hemolysis
- hyperbilirubinemia -> jaundice
- hyperbilirubinuria -> nephrosis
what metal is released into the blood under stress
copper
chronic copper poisoning is an inherited disease in ____________ (species of dog) due to a mutation in the gene _____________ that results in _________________
Bedlington terriers; COMMD1; impaired Cu excretion (accumulation) in hepatocytes and resultant hepatitis
how do we treat copper poisoning in sheep? in dogs?
sodium molybdate and sodium thiosulfate; D-penicillamine, triethylene tetramine dihydrochloride
Iron is an essential mineral for (3)
Hb, Mb, cytochromes
iron toxicity causes chronic ________ injury
hepatic injury (necrosis, fibrosis)
what form of iron is more readily absorbed
ferrous (2+) more than ferric (3+)
T/F heme iron is absorbed more readily than ferric iron
T
Iron has negative interactions with what 3 minerals
Cu, P, Zn
iron is distributed bound to ___________ and deposited in tissues as (2)
transferrin ; hemosiderin, ferritin
how is iron excreted
in sloughed intestinal epithelium; it is limited
what is the MOA of iron toxicity
oxidative stress -> lesions in liver and GI tract
what type of iron causes oxidative stress
free iron (i.e there is too much iron for the transport capacity of transferrin)
where does iron toxicity cause lesions (4); what is most common
liver, heart, pancreas, GI tract
liver most common
how many stages of iron toxicity are there
4
describe the signs for the following stages of iron toxicity:
Stage 1 (0-6h):
Stage 2 (6-24h):
Stage 3 (<4 days):
Stage 4: (2-6 weeks):
Stage 1 (0-6h): GI (vomiting, diarrhea, bleeding)
Stage 2 (6-24h): latent
Stage 3 (<4 days): lethargy, GI, hypotension, tachycardia, coagulation deficits, hepatic necrosis, +/- death
Stage 4: (2-6 weeks): healing ulcers, fibrosis, strictures
how do we diagnose iron toxicity
- history
- clinical signs
- elevated liver parameters
- PM lesions in liver and GI tract
- serum Fe analysis -> increased total serum Fe, increased TIBC, increased saturation of transferrin
how do we treat iron toxicity (4)
remove source, decontaminate, limit further absorption with milk of magnesia, chelate with deferoxamine mesylate
astragalus accumulates what metal
selenium
what are the signs of zinc toxicity
GI upset, renal failure, hemolysis, hemoglobinuria
what is caused by the following cases of selenium toxicity:
acute:
chronic:
acute: cardiovascular injury
chronic: lesions in hooves/skin/hair; weight loss; posterior paralysis; impaired immune system; reproductive effects
how do we diagnose selenium toxicity
history, clinical signs, quantification in serum/whole blood/tissue (liver), environment
what are the 2 chemical forms of mercury
inorganic (elemental, salts); organic (methylmercury)
what type of mercury is readily absorbed orally
methylmercury (organic mercury)
what are some sources of mercury
environment, paints, thermometers, fungicides, batteries
what are the 2 medicinal uses of mercury
amalgams for dentistry; antiseptics
T/F mercury bioaccumulates
T
what are the main MOA of mercury
crosses BBB causing neuronal degeneration, reduces protein synthesis, causes lipid peroxidation
what are the main clinical signs of mercury toxicosis (5)
GI irritation: nausea, vomiting, diarrhea
Cardiac: hypertension, tachycardia
CNS injury
acute and chronic kidney injury
reproductive problems
how do we diagnose mercury toxicosis
history, clinical signs, blood hb, heavy metals in tissue, non-specific lesions
give an example of the following forms of arsenic:
- inorganic
- organic
inorganic: naturally occurs in groundwater
organic: shellfish
what are some sources of arsenic
CCA treated lumber, herbicides, fungicides, groundwater, shellfish
is trivalent or pentavalent arsenic more toxic
trivalent
how is arsenic absorbed
orally or via skin
how is arsenic eliminated
urine, bile, feces, sweat
where does arsenic accumulate
liver
chronic exposure to arsenic results in accumulation where (3)
hair, nails, feathers
what is the MOA of arsenic
trivalent (arsenite) interferes with Krebs; pentavalent (arsenate) uncouples oxidative phosphorylation (no ATP production)
arsenic toxicosis impacts what body systems (4)
GI tract, cardiovascular, renal, CNS
how do we diagnose arsenic poisoning
levels in liver, kidney, feces, vomit, urine; organic arsenic in brain; exposure in hair and epidermis
what are 2 key toxic compounds in smoke and what do they do
carbon monoxide and cyanide -> cellular asphyxiation
what are the respiratory effects of the following:
- formaldehyde
- glutaraldehyde
formaldehyde: loss of cilia, necrosis, inflammation
glutaraldehyde: squamous metaplasia
carbon monoxide is the product of __________________ of ____________________
incomplete combustion; carbon containing fuels
what are some sources of carbon monoxide
internal combustion engines, fireplaces, gas or kerosene heaters, defective furnaces
blister beetles contain ___________, which causes
canthardin; vesicles and necrosis in the GI tract
biotoxins from spiders cause (3)
pain, muscle cramps, paralysis
biotoxins from caterpillars cause
placentitis and abortion in mares
venom from rattlesnakes contains (3), which causes (9)
phospholipases, myotoxic peptides, other toxins
causes:
- pain
- local necrosis and hemorrhage
- hemolysis and hemoglobinuria
- coagulopathy
- rhabdomyolysis
- myoglobinuria
- shock
- circulatory collapse
what do polychlorinated biphenyls (PCBs) do (2)
endocrine disruptors; carcinogens (some)
T/F polychlorinated biphenyls bioaccumulate and persist in the environment
T
