Heavy metals: Inorganic Arsenic Dr. Shokry

Question 1

General characteristics of heavy metals

Answer 1

Acute toxicosis: irritating/corrosive at high levels

damages GI mucosa so severe GI CS seen

very potent, very low levels needed for toxicosis

some are essential nutrients (components of metalloenzymes)

organic vs inorganic source can change CS & dz

Question 2

Inorganic Arsenic vs organic arsenic as far as type of systems affected

Answer 2

Inorganic arsenic has GI corrosive dz

vs

organic which give peripheral NS signs

Question 3

Sources of inorganic arsenic

Answer 3

Ant & roach baits Most common source in SA toxicosis

milk from poisoned cows may be toxic to calves

pastures near smelters may be contaminated

Question 4

properties of inorganic arsenic

Answer 4

elemental (arsenide) - poorly absorbed

trivalent (arsenite) - most toxic→ reacts with -SH group

pentavalent (arsenate) - least toxic but, usually metabolized to trivalent form

Question 5

toxicity of inorganic arsenic

types of toxicity

species affected

forms of inorganic arsenic

Answer 5

Very toxic 1-25 mg/kg LD in most spp

peracute, acute or subacute no chronic (exp humans)

herbivores most susceptible, dogs poisoned when eat ant/roach baits, swine & chickens rarely poisoned

inorganic trivalent toxicity > pentavalent toxicity > organic form

Question 6

toxicokinetics of inorganic arsenic

Answer 6

absorbed from GIT, inhalation & skin

distributed all over body except CNS; achieves higher conc in liver, kidney, hair, hoof, nail & skin

Doesn’t cross BBB

partly metabolized in liver & kidney (some bile excretion)

excreted in urine within 48 hrs

sm. amt excreted in feces, milk, saliva & sweat, hair & exhalation

Milk can have toxic levels (similar to lead & molybdemum)

Question 7

MoA of inorganic arsenic toxicosis

Answer 7

trivalent: binds to 2-SH groups of lipoic (thioctic acid)→ inhibition of lipoic acid inhibits glycolysis & citric acid cycle (decr energy!)→ inhibits ocxidative enzymes & inactivates glutathione (GSH)

pentavalent: uncouples oxidative phsphorylation (decr ATP)

local corrosive effect, intestine, liver, kidney are more sensitive, capillary endothelial cell most sensitive (hence hemorrhage)

Question 8

CS of inorganic arsenic toxicosis

Answer 8

Peracute: sudden death, severe colic, collapse & death

Acute: severe colic, diarrha (hemorrhagic), hematuria & death in 1-3 days

Subacute: colic, anorexia, diarrhea w/ blood or mucosal shreds, dehydration, hind limb paralysis

Question 9

Lesions inorganic arsenic toxicosis

Answer 9

GI mucosal edema & hemorrhage w/ sloughing & perforation

skin exposure causes skin lesions & blistering in addition to systemic lesions

Question 10

Lab dx of inorganic arsenic toxicosis

Answer 10

Urine best antemortem specimen

Liver & kidney best postmortem, > 7-10ppm in either organ strong indication

Question 11

Dx of inorganic arsenic toxicosis

Answer 11

Hx, sudden onset bloody diarrhea or watery w/ mucosal shreds, lesions & lab dx

Question 12

Tx inorganic arsenic toxicosis

Px

Answer 12

Emergency & supportive tx: IVF, tx acidosis

decontamination: gastric lavage (only early), mineral oil, act. charcoal, demulcents (kaolin-pectin)

chelation therapy:

dimercaprol (BAL), dimercatosuccinic acid (DMSA) - water soluble analog of BAL

Grave if not tx early