Tox, Heavy Metals

Front 1

__A__ is a by-product of Silver smelting.

__B__ comes from the melting of Copper and Tin.

__C__ is associated with ZnCarbonate as a contaminant

Back 1

A. Lead

B. Arsenic

C. Cadmium

Front 2

How do metals typically affect organisms?

Back 2

Usually affect multiple organ systems - but a low doses, it will primarily affect a specific organ

Front 3

Blood/Urine concentrations usually correlate best with?

Back 3

Recent Exposure and Acute Effects

*except urinary Cadmium --- may reflect renal damage related to ACCUMULATIONS of Cd in kidney

Front 4

Can the same metal have different toxicities in different situations?

Back 4

Yes - whether the metal is organic or inorganic may affect how it interacts with your enzymes and membranes.
**eg Organic Hg (fish) is a primary Neurotoxin -- but Mercuric Chloride is Nephrotoxic.

Front 5

Toxic metals and Essential metals have some interplay:

A. What metals use the same homeostatic mechanisms?
B. What metals have an inverse relationship with protein intake?
C. What affect does Vitamin C have on metals?
D. What metal interferes with Ca-dependent NT release?

Back 5

A. Pb, Ca, Fe

B. Pb, Cd

C. increases Fe, decreases Pb, Cd

D. Pb

Front 6

What protein binds Cd, Cu, Hg, Ag, and Zn?

What binds Ferric Iron in plasma?

What stores Ferrous Iron in tissues?

Back 6

Metallothioneins

Transferrin (also carries Al, Mn)

Ferritin (liver, spleen, bone)

Front 7

so then...how does that Ferric (3+) Iron become Ferrous (2+) Iron?

Back 7

Ceruloplasmin
a Cu-containing oxidase

Front 8

Define
A. Complexation
B. **Chelation** (clinical)

Back 8

A. formation of a metal ion complex in which the metal ion is assoc.w/ an e- donor ligand

B. formation of ring structures consisting of the metal ion and TWO ligand atoms - **more excretable form, get the metal out of the system

Front 9

Chelators:

BAL

Back 9

British Anti-Lewisite
(2,3-dimercaptopropanol)

Adjunctive Tx w/ Lead Encephalopathy. Also pulls Lead off of RBCs

Adverse: vomit, tremor, coma, death

Front 10

Chelators:

DMSA

Back 10

an analog of BAL

given Orally! also removes Lead from soft tissues..though does not get to brain-lead.

Front 11

Chelators:

EDTA

Back 11

always use CALCIUM-EDTA (Na-EDTA will cause hypocalcemia)
given Parenterally
binds Lead and displaces with Ca
not effective for brain-lead.

Adverse: nephrotoxic

Front 12

Trivalent Arsenic

Back 12

inhibits cell respiration (so tissue w/high E reqs /actively dividing are most affected)

affect capillary integrity

10x more toxic than Pentavalent

Front 13

Arsenic
effects who?
signs?

Back 13

gah Cats! >horses>rums>swine>birds

severe GI signs - vomit, pain, weakness, ataxia, recumbent, weak --> SHOCK
*kidney damage

**though some organic forms may target the CNS

Front 14

Arsenic - Tx for acute toxicosis?

Back 14

Dimercaprol (BAL)
Succimer (DMSuccinicAcid)
*Supportive Care

Front 15

Lead
A. where is it distributed?
B. mechanism?

Back 15

A. More than 90% of absorbed lead is bound to RBCs
B. binds sulfhydryl groups -> inactivates enzymes of heme synth
also damages Na/K pumps -> ***RBC damage and Kidney Damage***

Front 16

Lead
worse for young or adult?
absorption enhanced by deficiencies in?

Back 16

Young (like with most toxins)

Ca, Zn, Fe, VitD

Front 17

Lead

Clinical Signs
(Rums, Equids, Carnivores, Psittacines, Fowl/Raptors)

Back 17

Rums - CNS
Horses - Peripheral Neuropathy
Dog/Cat - GI and neurologic
Psittacines - GI, neuro, renal
Fowl/Raprots - Chronic Wasting

Front 18

Clin Path Hallmarks of Pb-toxicosis

Back 18

Basophilic Stippling
Large numbers of Nucleated RBCs
Anemia (w/chronic exposure)

Front 19

True or False

Whole Blood Lead Levels are indicative of severity of clinical signs.

Back 19

FALSE
blood level does not reflect whole body burden.

However - in general, >0.3 is significant and >0.6 is typically toxicosis.

Front 20

Lead / General Heavy Metal Tx:

What is a BIG rule for Chelation Therapy?

Back 20

besides DMSA (Succimer)

do NOT give Chelators until the Metal has been removed from the GI tract!! You may increase absorption of the metal if it is still in the lumen.

Front 21

Mercury

Back 21

not too common anymore - we've taken it out of all products, but it still pops up every once in awhile when an animal ingests an obsolete product.

Front 22

is playing with Mercury thermometers bad?

Back 22

actually...not really... in fact, eating it isn't too bad either (or a broken thermometer in the rectum)

**the problem is the VOLATILE form

Front 23

so what are the concerns then with Mercury?

Back 23

ORGANIC
methyl/ethyl forms are Lipophilic and readily absorbed. --Kidney
Alkyl forms cross BBB
All forms cross Placenta (fetus gets cerebellar hypoplasia)

Front 24

how nasty is a mercury spill in the dolphin tank?

Back 24

Marine mammals appear to have some ability to detoxify mercury!!

Front 25

Mercury Toxicosis -- Tx?

Back 25

Acute - Egg Whites (protein to bind with and pass out)
Cathartics (sorbitol)
DMSA (Succimer)
supplement Se and VitE

Front 26

so what's the deal with Mercury in Tuna?

Back 26

Irreversible Neurotoxicosis - beware!!
Hg contamination in fish is a big concern!

Front 27

Selenium... what does it cause?

Back 27

needs to be a HIGH HIGH dose

embryo (missing whole body parts) in aquatic birds
FPSP - Focal Porcine Symmetrical Poliomyelomalacia

Front 28

Selenium Dx?

Back 28

garlicky breath (but don't hang your hat on this)
go with signs --- hindlimb ataxia progressing to tetraparesis -- separation of hoof at coronary band

Front 29

DDx for Selenium?

Back 29

There are a ton!! Tough one, BOLO for many other diseases/toxicities.

Front 30

Copper

4 main ways Sheep suffer from Cu Toxicity.

Back 30

1. Fed Calf/Horse diet --> Excessive Dietary Cu

2. on Monensin --> increases absorption

3. drank from the footbath

4. Mo deficiency causes increased absorption of Cu

Front 31

Where is Cu absorbed - and where does it go in the body?

Back 31

monogastric - stomach and SI
rums - lower SI

Copper transported to enterocytes -> albumin/ceruloplasmin/transcuprein -> LIVER and KIDNEY and brain

Front 32

How does it cause damage?

Back 32

Liver can hold a lot --- but when you hit threshold - Liver Necrosis --> massive flood of Copper into bloodstream
*erythrolysis, hemoglobinuria, high serum Cu
--> THEN it accumulates in the Kidneys (end-stage) --> Gun Metal Black Kidneys

Front 33

Toxic Levels for Sheep?

Back 33

30-50 ppm

generally no clinical signs until stressful event pushes liver to blow.

Front 34

Copper Tox in Dogs?

Back 34

Bedlingtons, WHighWhites, Skye Terriers

slow development of chronic active hepatitis

Front 35

Treatment of Copper Tox?

Back 35

Rums usually dead already....or Tx is unsuccessful

Dogs - D-penicillamine promotes urinary excretion of copper

Front 36

Molybdenum

what is it needed for?

Back 36

required for xanthine enzymes as well as sulfite oxidase
three way interaction with copper and sulfur
Rums more sensitive (cattle mostly, deer most rz)

Front 37

What effect does a high sulfur diet have on rums?

Back 37

Increase Mo absorption

Decrease Cu absorption

Front 38

Molybdenum

Signs of toxicity?

Dx?

Back 38

Chronic Diarrhea

Emaciation, relative Cu deficiency, CT/Bone abnormalities, Abortions

Liver - High Mo, Low Cu

Front 39

Fluoride

Source?

Back 39

Phosphate Supplements (which should be defluorinated)

Front 40

Fluoride

Where does it go?
and what does it do?

Back 40

Bone and Kidney

Fl replaces Hydroxyapatite - delaying and altering mineralization (organic oxidation = brown/black teeth)
Excessive Bone Remodeling of Long Bones

Front 41

Acute Fluoride Toxicosis

Chronic Fluorosis

Back 41

Excitation, Urinary/Fecal incontinence, cardiac failure, death

dry haircoat, dry skin, weight loss

Front 42

Iron

Back 42

most abundant trace mineral in the body
sources - supplements, fertilizers and soil

Front 43

Iron Toxicosis

Back 43

Direct Corrosion of GI tract --> increased presence of unbound blood Fe --> Lipid Peroxidation --> membrane damage (fatty necrosis of MYOCARDIUM), reduced CO, increased cap. permeability

Front 44

Iron Excretion

Back 44

There is NO NORMAL mech to eliminate Iron

So try to convert the elemental iron ingested into an iron salt (less severe form of Iron)

Front 45

Level of Iron for Toxicosis?

Back 45

Dogs - 20 mg/kg nontoxic, over 60 = serious signs

All animals 100-200 mg/kg is potentially lethal

Front 46

Define

A. Hemochromatosis

B. Hemosiderosis

Back 46

A. Pathologic tissue accumulation of Iron

B. Non-Pathologic accumulation of Iron

Front 47

Four Clinical Phases of Fe Toxicosis:

Back 47

Stage 1: 0-6hrs
vomit, diarrhea, GI bleed

Stage 2: 6-24hrs
transient/latent period

Stage 3: 12-96hrs
Clinical signs - CV signs, liver damage, possibly Death

Stage 4: 2-6 weeks
GI ulceration, possibly strictures

Front 48

Iron Tox Diagnosis?

Back 48

Serum Iron Level and TIBC (total Iron binding capacity)

if Serum Iron > TIBC, you may have severe systemic trouble

Front 49

Iron Tox Treatment?

Back 49

AC is NOT effective
...but Anatacids help to precipitate Fe to nonabsorbable form in GI
(NaPO4, NaHCO2, MgOH)

Supportive Care
+/- Chelation if severe (Deferoxamine)

Front 50

Sodium Toxicosis

Back 50

gastroenteritis, e- imbalance, severe dehydration (>10%)

Hypernatremia -- Sodium PASSIVELY enters CSF, but must be ACTIVELY pumped out --> E-deficiency, Na trapped in Brain

...now dehydrated animal is given water --> Cerebral Edema

ACUTE DEATH

Front 51

Sodium Toxicosis Treatment

Back 51

Replace H2O deficit SLOWLY (over several days)
~0.5% body weight in water at 1 hour intervals

Front 52

Zinc

Sources

Back 52

Nuts/Bolts, ZnO2 ointments, Pennies from 1983 on, Galvanized containers, pipes, etc...

Front 53

Zinc

Absorbed where?
Interactions with?
Excreted?

Back 53

Duodenum
Copper decreases Zn absorption and vice versa
Feces (chelated Zn in Urine)

Front 54

Zinc Toxicosis

Back 54

Severe Intravascular Hemolysis

samples in Royal-Blue Top tubes
(most other tubes have some Zn in their rubber)

Front 55

Zinc Toxicosis Treatment?

Back 55

Remove foreign bodies (endoscopy/Sx)
Supportive Care
+/- Chelation