Test 4: 57-58 heavy metals Flashcards
1
Q
Inverse relationship between dietary protein content and — toxicity
A
cadmium and lead
2
Q
Vitamin C increases — absorption while decreasing absorption of —
A
ferrous iron
lead and cadmium
3
Q
metal binding proteins may be a target of toxicity (especially enzymes) or play a protective
role (—)
A
metallothioneins
4
Q
— are low molecular weight proteins that enable high-affinity binding with cadmium, copper, mercury, silver, and zinc
A
Metallothioneins
5
Q
Transferrin binds most — in plasma
A
ferric iron
Ferric transferrin is transported across cell membranes by receptor-mediated endocytosis
- Transferrin also transports Al3+ and Mn2+
6
Q
Ferritin stores iron in reticuloendothelial cells of —
A
liver, spleen, and bone
Also binds cadmium, zinc, beryllium, and aluminum
7
Q
— is a copper-containing glycoprotein oxidase that converts
ferrous (Fe2+) to ferric (Fe3+) iron
in plasma so it can then bind to —
A
Ceruloplasmin
transferrin
8
Q
— is the formation of a metal ion complex in which the metal ion is associated with a charged or uncharged electron donor ligand
A
Complexation
9
Q
is the formation of ring structures consisting of the metal ion and 2 ligand atoms
A
chelation
10
Q
ideal chelating agents should
A
- 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
11
Q
BAL is used to chelate
A
lead, inorganic mercury, antimony, bismuth, chromium, cobalt, gold, and nickel
adjunct treatment of lead
encephalopathy- removed lead from RBC and brain
12
Q
BAL toxicosis
A
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
13
Q
sodium EDTA will do what to calcium levels
A
binds to calcium and will cause ↓calcium tetany
14
Q
calcium EDTA is different from BAL because
A
BAL can chealte lead in brain
EDTA can not get into brain
drugs can be combined together
15
Q
DMSA
A
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
16
Q
deferoxamine binds to —
A
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
17
Q
toxic effects of deferoxamine
A
nausea, vomiting, depression, hypotension, skin rashes, and possibly cataracts
used to bind to ferric iron
18
Q
penicillamine is used to remove
A
copper, lead, mercury, and iron
19
Q
— should not be used in pts with penicillin allergy
A
penicillamine: used for removal of copper, lead, mercury, and iron
20
Q
N-Acetylcysteine is used to remove
A
mercury, methyl mercury and other metals
Free radical scavenger and precursor to glutathione
21
Q
— is a free radical scavenger and precursor to glutathione that is used to remove mercury
A
N- Acetylcysteine
Orally administered, low toxicity, and widely available
22
Q
— arsenicals inhibit cellular respiration
A
trivalent
23
Q
trivalent arsenic affect what type of cells
A
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
24
Q
trivalent or pentavalent forms of arsenic are more toxic
A
trivalent: inhibit cellular respiration and affect capillary integrity in GI tract
25
how does pentavalent arsenic work
substitute for
phosphate in oxidative phosphorylation
causes ↓ATP, **does NOT cause ↑temp**
26
The hydride gas of arsenic, AsH3, can combine with hemoglobin and be oxidized to a ---
hemolytic metabolite
27
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
28
--- toxicity can present with animals assume a dog-sitting position with appetite and cognition remaining normal
arsenic
29
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
30
More than 90% of absorbed lead is bound to ---
RBCs
31
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
32
Lead toxicity
--- will have CNS signs
ruminants
33
Lead toxicity
--- will have peripheral neuropathies signs
horses
34
dogs and cats with lead toxicity will present with
neuro and GI signs
35
parrots with lead toxicity will present with
nonspecific GI, neurologic,
renal, and hematologic
abnormalities
36
Basophilic stippling can be normal in ---, though may be more
diagnostic of --- toxicity in dogs and horses
ruminants
lead
37
Large numbers of --- without evidence of severe anemia can be suggestive of lead toxicosis in small animals
nucleated RBCs
38
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
39
--- mercury is excreted primarily in urine and causes direct tissue necrosis and renal tubular necrosis
Inorganic mercury
40
--- mercurials are excreted mainly in bile and feces
Organic
41
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
42
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
43
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
44
Domestic livestock and companion animals may become intoxicated with --- after parenteral overdose
selenium
45
Selenium-containing compounds have biological importance as an ---
essential dietary constituent
46
Intoxication can result from excess selenium supplementation of --- rations
livestock
47
The --- is the primary site of selenium absorption, with little or no absorption occurring from the ---
duodenum
rumen or abomasum
48
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
49
Acute selenium intoxication usually manifests as
depression, weakness, dyspnea, and a **garlicky odor to the breath**
50
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
51
what caused the hair to break
too much selenium
52
Chronic intoxication, or “alkali disease,” results from chronic
consumption of ---grasses and crops
seleniferous
53
selenium will cause lesion in the ---
heart
54
Dietary --- deficiency can result in excessive absorption and storage of copper
molybdenum
55
Feeding calf or horse rations to --- is a common source of excessive dietary copper
sheep
56
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
57
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)
58
copper
gun metal kidney
excess copper accumulates in the kidney
59
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
60
what kind of dogs can have hereditary copper hepatitis
bedlington terriers
labs
dobermanns
west highland white terriers
dalmatian
61
--- has a three-way interaction with copper and sulfur
Molybdenum
62
Molybdenum is required for metalloenzymes, including ---, xanthine dehydrogenase, aldehyde oxidase, and sulfite oxidase
xanthine
oxidase
63
Diets high in sulfur --- copper absorption and --- susceptibility to molybdenum
decrease
increase
64
Diets high in molybdenum may --- absorption of zinc
decrease
65
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
66
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
67
clinical signs of acute fluoride toxicosis
excitation, seizures, urinary and fecal incontinence, vomiting, weakness, hypersalivation, depression, cardiac failure, and death
68
Aluminum sulfate, aluminum chloride, calcium aluminate, and calcium carbonate can be used to reduce absorption of --- in the diet
fluorides
69
Iron toxicosis is usually due to excessive injections in --- or the ingestion of large amounts of iron-containing products in other species
baby pigs
70
Iron is most toxic when given ---
intravenously
71
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
72
Iron must be in --- state for absorption
an ionized
73
In acute overdoses, iron seems to be absorbed in a --- fashion
passive, concentration-dependent
usually needs energy dependent carrier (transferrin-like protein
74
70% of iron is in the --- form when bound to normal hemoglobin and myoglobin
ferrous (Fe2+)
75
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+)
76
Most iron is stored in the ---
liver, spleen, and bone marrow
77
at a cellular level, excess free iron causes
**increased lipid peroxidation** with resulting membrane damage to mitochondria, microsomes, and other cellular organelles
78
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**
79
There is not a mechanism for excretion of ---, so toxicity depends on the amount already present in the body
iron
80
what level of iron is lethal for dog
less than 20- nontoxic
20-60: mild clinical signs
↑60: serious signs
**100-200: deadly**
81
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**
## Footnote
less than 20- nontoxic
20-60: mild clinical signs
↑60: serious signs
**100-200: deadly**
82
is pathologic tissue accumulation of iron
Hemochromatosis
83
is non-pathologic accumulation of iron
Hemosiderosis
84
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
85
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
86
peracute syndrome in pigs is characterized by sudden death is caused by excess ---
iron (injection given IV?)
87
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
88
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
89
how to treat severe iron toxicosis
chelation: **Deferoxamine (Desferal)**
90
indirect vs direct sodium toxicosis
direct: eating too much salt
indirect: not enough water
91
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
92
excess sodium can passively diffuse into the
CSF
93
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
94
Although sodium --- enters the CSF, it is --- transported back out into serum
passively
actively
95
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**
96
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
97
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**
98
how to diagnosis excess salt
serum and CSF sodium levels
postmortem: eye fluids and brain tissue
99
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
