Test 4: 57-58 heavy metals Flashcards
Inverse relationship between dietary protein content and — toxicity
cadmium and lead
Vitamin C increases — absorption while decreasing absorption of —
ferrous iron
lead and cadmium
metal binding proteins may be a target of toxicity (especially enzymes) or play a protective
role (—)
metallothioneins
— are low molecular weight proteins that enable high-affinity binding with cadmium, copper, mercury, silver, and zinc
Metallothioneins
Transferrin binds most — in plasma
ferric iron
Ferric transferrin is transported across cell membranes by receptor-mediated endocytosis
- Transferrin also transports Al3+ and Mn2+
Ferritin stores iron in reticuloendothelial cells of —
liver, spleen, and bone
Also binds cadmium, zinc, beryllium, and aluminum
— is a copper-containing glycoprotein oxidase that converts
ferrous (Fe2+) to ferric (Fe3+) iron
in plasma so it can then bind to —
Ceruloplasmin
transferrin
— is the formation of a metal ion complex in which the metal ion is associated with a charged or uncharged electron donor ligand
Complexation
is the formation of ring structures consisting of the metal ion and 2 ligand atoms
chelation
ideal chelating agents should
- Be water-soluble
- Be resistant to biotransformation
- Be able to reach sites of metal storage
- Be capable of forming nontoxic metal complexes
- Be capable of being excreted
- Have a low affinity for essential metals, especially calcium and zinc
BAL is used to chelate
lead, inorganic mercury, antimony, bismuth, chromium, cobalt, gold, and nickel
adjunct treatment of lead
encephalopathy- removed lead from RBC and brain
BAL toxicosis
vomiting, hypertension, tachycardia, tremors, convulsions, and coma, culminating in death
Potentially nephrotoxic
BAL: adjunct treatment of lead
encephalopathy: chelate lead, inorganic mercury, antimony, bismuth, chromium, cobalt, gold, and nickel
sodium EDTA will do what to calcium levels
binds to calcium and will cause ↓calcium tetany
calcium EDTA is different from BAL because
BAL can chealte lead in brain
EDTA can not get into brain
drugs can be combined together
DMSA
used to chelate lead (not effective in brain)
can be given orally, not nephrotoxic
also effective in dogs exposed to methyl mercury and lead, and mice, rats, and rabbits exposed to arsenic
deferoxamine binds to —
ferric (Fe3+) iron
Competes for iron contained in ferritin and hemosiderin, but not transferrin, hemoglobin, or heme-containing enzymes
will change urine to vin rose when working
toxic effects of deferoxamine
nausea, vomiting, depression, hypotension, skin rashes, and possibly cataracts
used to bind to ferric iron
penicillamine is used to remove
copper, lead, mercury, and iron
— should not be used in pts with penicillin allergy
penicillamine: used for removal of copper, lead, mercury, and iron
N-Acetylcysteine is used to remove
mercury, methyl mercury and other metals
Free radical scavenger and precursor to glutathione
— is a free radical scavenger and precursor to glutathione that is used to remove mercury
N- Acetylcysteine
Orally administered, low toxicity, and widely available
— arsenicals inhibit cellular respiration
trivalent
trivalent arsenic affect what type of cells
inhibit cellular respiration:
Actively dividing cells of the intestinal epithelium, epidermis,
kidney, liver, skin, and lung
Trivalent arsenic also affects capillary integrity in GI tract
trivalent or pentavalent forms of arsenic are more toxic
trivalent: inhibit cellular respiration and affect capillary integrity in GI tract
how does pentavalent arsenic work
substitute for
phosphate in oxidative phosphorylation
causes ↓ATP, does NOT cause ↑temp
The hydride gas of arsenic, AsH3, can combine with hemoglobin and be oxidized to a —
hemolytic metabolite
clinical signs of arsenic posioning
Vomiting, intense abdominal pain,
weakness, staggering, ataxia, recumbency, and weak, rapid pulses with signs of shock are common
dog-sitting position with appetite and cognition remaining normal
— toxicity can present with animals assume a dog-sitting position with appetite and cognition remaining normal
arsenic
treatment for arsenic
Emergency and supportive care consist of treatment for shock, acidosis, and dehydration
* Dimercaprol (British anti-Lewisite, or BAL) is the classic antidote, but is largely ineffective unless
given before clinical signs begin
* Succimer is currently the preferred antidote
* Convalescent animals should be fed bland diets with vitamin supplementation and reduced amounts of high-quality protein
More than 90% of absorbed lead is bound to —
RBCs
lead toxicity works by
Lead binds sulfhydryl groups, resulting in the inactivation of enzymes involved in heme synthesis, causing RBC abnormalities
- Damage to membrane-associated enzymes such as sodium-potassium pumps results in RBC fragility and renal tubular injury
- Shortened RBC lifespan and decreased replacement both contribute to the anemia seen
with chronic lead toxicosis
Lead toxicity
— will have CNS signs
ruminants
Lead toxicity
— will have peripheral neuropathies signs
horses
dogs and cats with lead toxicity will present with
neuro and GI signs
parrots with lead toxicity will present with
nonspecific GI, neurologic,
renal, and hematologic
abnormalities
Basophilic stippling can be normal in —, though may be more
diagnostic of — toxicity in dogs and horses
ruminants
lead
Large numbers of — without evidence of severe anemia can be suggestive of lead toxicosis in small animals
nucleated RBCs
treatment of lead toxicity
- Stabilization
- Elimination of lead from the GI tract
- Chelation: Succimer(DMSA) or CaEDTA +/- BAL and/or thiamine
- General supportive care
- Elimination of lead from the animal’s environment
— mercury is excreted primarily in urine and causes direct tissue necrosis and renal tubular necrosis
Inorganic mercury
— mercurials are excreted mainly in bile and feces
Organic
clinical signs of mercury toxicosis
stomatitis, pharyngitis, vomiting, diarrhea, dehydration, and shock
◼ Early signs: erythema of the skin, conjunctivitis, lacrimation, stomatitis ◼ Intermediate signs: depression, ataxia, incoordination, paresis, blindness
◼ Dermatitis, pustules, and epithelial ulcers increase
during the course of the disease
◼ Anemia can result because of hematuria and melena
◼ Advanced signs: proprioceptive defects, abnormal postures, complete blindness, anorexia, paralysis, slowed respiration, coma, death
In acute exposure to elemental mercury or mercuric salts, — may be administered to bind ingested mercury; oral sodium thiosulfate also binds mercury
egg white or activated charcoal
treatment of mercury
egg white or activated charcoal
cathartic or sorbitol
penicillamine
DMSA (succimer)
Supplemental selenium and vitamin E are somewhat protective against mercury toxicosis
Domestic livestock and companion animals may become intoxicated with — after parenteral overdose
selenium
Selenium-containing compounds have biological importance as an —
essential dietary constituent
Intoxication can result from excess selenium supplementation of — rations
livestock
The — is the primary site of selenium absorption, with little or no absorption occurring from the —
duodenum
rumen or abomasum
Porcine focal symmetrical poliomyelomalacia (PFSP) results from an induced deficiency of nicotinamide as well as from — intoxication, suggesting the involvement of oxidative metabolic failure in the pathogenesis of the lesion
selenium
Acute selenium intoxication usually manifests as
depression, weakness, dyspnea, and a garlicky odor to the breath
Subchronic selenium intoxication in pigs manifests as a
CNS disorder characterized by initial hindlimb ataxia progressing to posterior paralysis, then
tetraparesis to paralysis
* Affected pigs remain alert and attempt to walk while dragging their hindlimbs
* Hoof separation at the coronary band also occurs
what caused the hair to break
too much selenium
Chronic intoxication, or “alkali disease,” results from chronic
consumption of —grasses and crops
seleniferous
selenium will cause lesion in the —
heart
Dietary — deficiency can result in excessive absorption and storage of copper
molybdenum
Feeding calf or horse rations to — is a common source of excessive dietary copper
sheep
Copper is actively transported through the enterocytes, then loosely binds to —, ceruloplasmin, and transcuprein before being distributed to the — for storage
albumin
liver, kidney, and brain
Excess liver copper levels can cause liver necrosis and release of the copper into the bloodstream, resulting in — in the serum
erythrolysis, hemoglobinuria, and elevated copper levels
(copper levels can be transient)
copper
gun metal kidney
excess copper accumulates in the kidney
sheep with copper toxicity will show — clinical signs
when stressed
- Intravascular hemolysis results in hemoglobinuria, icterus, anoxia, and death
- Urine is dark red with a “port wine” appearance due to the presence of hemoglobin
what kind of dogs can have hereditary copper hepatitis
bedlington terriers
labs
dobermanns
west highland white terriers
dalmatian
— has a three-way interaction with copper and sulfur
Molybdenum
Molybdenum is required for metalloenzymes, including —, xanthine dehydrogenase, aldehyde oxidase, and sulfite oxidase
xanthine
oxidase
Diets high in sulfur — copper absorption and — susceptibility to molybdenum
decrease
increase
Diets high in molybdenum may — absorption of zinc
decrease
clinical signs of molybdenum
chronic diarrhea
A relative copper deficiency causes abnormalities in connective tissue formation and bone
- Abnormal bone growth and parostosis
In addition to copper deficiency, abortions have been observed in pregnant mares
clinical signs of fluoride
Fluorides replace hydroxyapatite,
delaying and altering mineralization of bone
- Erupting incisors and molars are weaker than normal teeth and wear rapidly
- Oxidation of organic material in damaged portions of the teeth causes brown or black discoloration
- bones remodel and deform → subperiosteal hyperostosis with thickened and irregular long bone surfaces
clinical signs of acute fluoride toxicosis
excitation, seizures, urinary and fecal incontinence, vomiting, weakness, hypersalivation, depression, cardiac failure, and death
Aluminum sulfate, aluminum chloride, calcium aluminate, and calcium carbonate can be used to reduce absorption of — in the diet
fluorides
Iron toxicosis is usually due to excessive injections in — or the ingestion of large amounts of iron-containing products in other species
baby pigs
Iron is most toxic when given —
intravenously
how is iron absorbed
First, ferrous ions are absorbed from the intestinal lumen into the mucosal cells (energy dependent carrier: transferrin-like protein moves ferrous iron into mucosal cells
The second step is the transfer of iron to ferritin or into circulation bound to transferrin proteins
* Complexed with transferrin, iron is distributed to other storage locations in the body
Iron must be in — state for absorption
an ionized
In acute overdoses, iron seems to be absorbed in a — fashion
passive, concentration-dependent
usually needs energy dependent carrier (transferrin-like protein
70% of iron is in the — form when bound to normal hemoglobin and myoglobin
ferrous (Fe2+)
Most of the remaining iron not bound to hemoglobin and myoglobin is found in the body as the — form, stored in hemosiderin, ferritin, and transferrin
ferric (Fe3+)
Most iron is stored in the —
liver, spleen, and bone marrow
at a cellular level, excess free iron causes
increased lipid peroxidation with resulting membrane damage to mitochondria, microsomes, and other cellular organelles
what does excess iron do to the heart
fatty necrosis of the myocardium, postarteriolar dilation, increased capillary permeability, and reduced cardiac output
also interferes with clotting mechanisms and causes metabolic acidosis
There is not a mechanism for excretion of —, so toxicity depends on the amount already present in the body
iron
what level of iron is lethal for dog
less than 20- nontoxic
20-60: mild clinical signs
↑60: serious signs
100-200: deadly
if a 10 kg dog eats 200 mg of ferric pyrophosphate
FP is 30% elemental iron
Toxic?
200 mg ( 0.3)= 60 mg elemental iron
60 mg/10 kg dog= 6 mg/kg elemental iron
less than 20- nontoxic
less than 20- nontoxic
20-60: mild clinical signs
↑60: serious signs
100-200: deadly
is pathologic tissue accumulation of iron
Hemochromatosis
is non-pathologic accumulation of iron
Hemosiderosis
four clinical phases of iron toxicosis
what is 1 and 2
First stage: occurs between 0 and 6 hours post-exposure
* Vomiting, diarrhea, and GI bleeding
* Most animals with mild to moderate iron toxicosis do not progress beyond this stage
Second stage: occurs 6-24 hours post- exposure
* Transient latent period
four clinical phases of iron toxicosis
what is 3rd and 4th
Third stage: occurs about 12-96 hours after clinical signs develop
* Lethargy, recurrence of GI signs, metabolic acidosis, shock, hypotension, tachycardia, cardiovascular collapse, coagulation deficits, and hepatic necrosis
* Death may occur
Fourth stage: occurs 2-6 weeks later in animals that develop GI ulcerations
* As ulcerations heal, scarring and strictures may develop
peracute syndrome in pigs is characterized by sudden death is caused by excess —
iron (injection given IV?)
Serum iron levels are the best method to confirm iron poisoning, and it is also beneficial to measure the —
total iron- binding capacity (TIBC)
When serum iron exceeds the TIBC,
severe systemic effects can be expected
how to treat acute iron toxicity
acute: GI decontamination, activated charcoal does not work, can use sodium phosphate, sodium bicarbonate, or magnesium hydroxide instead
GI protectants: sucralfate
supportive: fluids
how to treat severe iron toxicosis
chelation: Deferoxamine (Desferal)
indirect vs direct sodium toxicosis
direct: eating too much salt
indirect: not enough water
Hypernatremia occurs when the sodium content of the extracellular fluid (ECF) increases in relation to — or — from the ECF without a compensatory decrease in sodium
its free water content
free water is lost
excess sodium can passively diffuse into the
CSF
what happens to CNS with excess salts
the brain cells shrink from dehydration, tearing blood vessels that lead to hemorrhage, brain infarcts, and cerebral edema
Although sodium — enters the CSF, it is — transported back out into serum
passively
actively
if sodium is trapped in brain cause it can not be actively transported back and you give unlimited water, what will happen?
water will move into brain to try to balance salt
cerebral edema
with excess sodium, Organic solutes called — increase to maximum levels within 48-72hours and a similar amount of time is required for their decline as a hypernatremic crisis is resolved
idiogenic osmoles
in swine early clinical signs of excess sodium are
- restlessness, thirst, pruritus, constipation, and vomiting, aimless wandering, blindness, head pressing, and circling
- Muscle twitches start at the snout then spread to the head
- As tremors progress, pigs assume a dog-sitting position before falling over into lateral recumbency
with seizures and opisthotonos followed by death
how to diagnosis excess salt
serum and CSF sodium levels
postmortem: eye fluids and brain tissue
how to treat excess salt
slowly rehydrate to prevent cerebral edema
0.5% body weight of water every hour
Cerebral edema may require treatment with mannitol or glycerin
50% die
