Chronic heavy metal poisoning - Arsenic, Lead, Copper, Iron, Mercury

1. CHRONIC HEAVY METAL
POISONING
Presented by- Rhea Joseph
PD412
Pharm D
Subject: Clinical Toxicology

2. Heavy metals
Metallic elements in trace quantities are essential for various biological
processes.
- activate enzymes
- facilitate exchange and utilization of oxygen and carbon dioxide.
Common source
Through food, excessive exposure (nutritional, occupational, or
environmental)
progressive accumulation and toxicity
serious consequences.

3. Arsenic
- Twentieth most common element in the earth’s crust, having a concentration
of 1.8 ppm.
- Commonest source of acute heavy metal poisoning, and is second only to
lead in the incidence of chronic toxicity.
PHYSICAL APPEARANCE
Arsenic is a metalloid.
Silver-grey or tin-white, shiny, brittle,
crystal- line and metallic-looking element.
USUAL FATAL DOSE
- 200 to 300 mg for arsenic trioxide.
- Arsenate (pentavalent form) <TOXIC arsenite (trivalent form)
Reason- less water soluble.
- The most toxic form is arsine gas (25 to 30 ppm can be lethal in 30 minutes).

4. TOXICOKINETICS AND MODE OF ACTION
Absorption - oral, inhalational, and cutaneous routes
redistributed to the liver, lungs, intestinal wall, and spleen
binds to the sulfydryl groups of tissue proteins  replaces phosphorus in the
bone, deposited also in hair
*doesn’t cross BBB, but crosses placenta readily.
intrauterine death of the foetus
less severe intoxications it can cause respiratory distress of the newborn

5. CLINICAL FEATURES

6. DIAGNOSIS
1. Urine level
If the 24 hour excretion of arsenic exceeds 100 mcg, it is indicative of toxicity.
• However, ingestion of seafood can interfere with interpretation since
considerable concentrations of organic arsenicals such as arsenobetaine and
arsenocholine may be present in shellfish, cod, haddock, etc., although it is
not associated with toxic effects. In such cases, the analysis must be
repeated after 2 days of “no fish” diet.
2. Blood level
Less reliable than urine level
Blood level of arsenic < 7 mcg/100 mL (70 mcg/L) is generally considered in
the normal range.
3. Hair level
Cannot discriminate between external deposition and toxic accumulation,
pubic hair instead of scalp hair should be sent for quantitation.

7. 4. Radiography
Since arsenic is radiopaque, abdominal x-ray
may reveal its presence in the gastrointestinal tract in acute poisoning.
5. Additional investigations
a. Monitor CBC, serum electrolytes, urinalysis (for proteinuria, haematuria
or pyuria), liver and renal function tests.
b. Obtain an ECG and institute continuous cardiac monitoring in
symptomatic patients.
c. Obtain a chest radiograph in patients with severe poisoning or pulmonary
effects.
d. Initial and periodic biological monitoring and medical surveillance are
required for employees exposed to arsenic.

8. TREATMENT
1. Supportive measures: gastric lavage, intravenous fluids, cardiac
monitoring, etc.
2. Chelation therapy: This can be done with BAL (British Anti Lewisite
or dimercaprol), penicillamine, DMSA (Dimercapto succinic acid),
or DMPS (Dimercapto propane sulfonic acid).
The usual agent employed is BAL at a dose of 3 to 5 mg/kg
intramuscularly every 4 hours until the urinary arsenic excretion dips
below 50 mcg/24 hours. Usual duration of therapy is 7 to 10 days.
In patients who are not allergic to penicillin, penicillamine can be given
orally at a dose of 100 mg/kg/day, 6th hourly for 5 days.
3. Haemodialysis or exchange transfusion.
CASE STUDY: A devastating health crisis (endemic hydroarsenicism)
began to unfold in West Bengal in the early 1980s due to exposure to
arsenic laced well water.

9. Lead
Commonest metal involved in chronic poisoning.
One of the first metals known to man, widely used for domestic, industrial, and
therapeutic purposes.
PHYSICAL APPEARANCE
Elemental lead - highly lustrous, heavy, silvery-grey metal, bluish tint as it
tarnishes in air.
Quite soft and malleable.
Its salts occur as variously coloured powders or liquids and are used widely in
industry and at home, producing cumulative toxicity on chronic exposure.
Uses:
sugar of lead sindoor
white lead surma
litharge

10. USUAL FATAL DOSE
The average lethal dose is said to be 10 gm/70 kg
100 mg/kg for tetraethyl lead.
TOXICOKINETICS
Absorption – oral, inhalation, skin
Stored in bones as phosphate and carbonate.
Accumulated in radius, tibia, and femur
“lead lines” observed on x-ray
skeletal lead are released from bone into the blood stream  toxicity
symptoms
Excreted primarily in the urine (about 65%) and bile (about 35%).

11. MODE OF ACTION
- Lead combines with sulfhydryl enzymes  decreases haeme synthesis by
inactivating the enzymes involved  results in anaemia.
- Increases haemolysis - immature red cells are released into circulation
- CNS  oedema  decreased nerve conduction
- CVS, Kidney, reproductive organs, gout.
CLINICAL FEATURES
a. Mild toxicity (BL 40-60 mcg/100ml)
– Myalgia
– Paraesthesia
– Fatigue
– Irritability
– Abdominal discomfort.

12. b. Moderate Toxicity (BL 60 to 100 mcg/100 ml) :
– Arthralgia (especially nocturnal)
– Muscular exhaustibility
– Tremor
– Headache
– Diffuse abdominal pain
– Anorexia, metallic taste, vomiting – Constipation
– Weight loss
– Hypertension.
c. Severe Toxicity (BL more than 100 mcg/100 ml) :
– Lead palsy: Wrist drop or foot drop
– A bluish black lead line on gums (Burton’s line)
– Lead colic: Intermittent severe abdominal cramps.
– Lead encephalopathy

13. DIAGNOSIS
1. Blood
2. Urine
3. Bone
TREATMENT
1. Severe acute poisoning with encephalopathy:
a. BAL 4 mg/kg immediately (in children).
b. Cranial CT scan, if cerebral oedema
- Diuretics
» Mannitol 20%: Adult: 1 to 1.5 gm/kg by infusion over 10 to 20 minutes. Child:
0.5 to 1 gm/kg by IV infusion over 10 to 20 minutes.
» Glycerol: 0.3 to 1 gm/kg orally.
» Loop Diuretics: Furosemide and/or ethacrynic acid (as an adjunct)
» Corticosteroids: Dexamethasone
low dose - 16 mg/day in divided doses.
high dose— 1 to 2 mg/kg/day in divided doses.

14. c. KUB: to rule out lead chips in GI tract.
d. For seizures: intravenous diazepam
e. Foley catheterisation
f. CaNa2 EDTA 75 mg/kg/day IV infusion.

15. Copper
PHYSICAL APPEARANCE
lustrous, ductile, malleable, odourless solid with a distinct golden-red or reddish-
brown colour.
Third most abundant trace element in the body
Important catalyst for heme synthesis and iron absorption.
USUAL FATAL DOSE
About 10 to 20 grams of copper sulfate.
DIAGNOSIS
1. Serum caeruloplasmin level
2. Blood copper level
3. Urine level
4. Radiography

16. CLINICAL FEATURES
a. Chronic inhalation of copper sulfate cause vineyard sprayer’s lung disease 
histiocytic granulomatous lung.
Liver damage is also common.
b. Chronic contact with swimming pool water containing algicidal copper
chemicals  green hair discolouration.
c. Cooking in copper or brass vessels;
leaching of copper containers in which carbonated water, citrus fruit juices, and
other acidic beverages have been stored.
copper poisoning due to verdigris.
d. Chronic copper toxicity -- hallmark of Wilson’s disease,
an autosomal recessive genetic disorder in which there is deficiency of
caeruloplasmin. Discolouration of the peripheral part of the cornea by deposition
of copper in parenchymal tissue.
e. Metal fume fever, wheezing and rales.
f. Skin exposure can produce severe irritation, itching, erythema, dermatitis and
eczema.

17. TREATMENT
1. Haemodialysis
2. Administration of egg white or milk orally
3. Stomach wash
4. Use of chelators
D-penicillamine
Dimercaprol
Unithiol
Calcium disodium edetate
5. Symptomatic measures
6. Eye exposure
7. Dermal exposure
8. Disorder of hair colour

18. Iron
PHYSICAL APPEARANCE
silvery white in colour
it is an essential element and deficiency results in anaemia.
USUAL FATAL DOSE
The usual fatal dose corresponds to about 200 to 250 mg of elemental iron per
kg of body weight.
TOXICOKINETICS
Iron poisoning occurs when serum iron level exceeds the total iron-binding
capacity (TIBC), resulting in free circulating iron in the bloodstream.

19. MODE OF ACTION
Free Iron causes:
Massive postarteriolar dilatation which results in venous pooling.
Increased capillary permeability resulting in decreased plasma volume.
Oxidation of ferrous to ferric iron releasing hydrogen ions.
Subsequent hydration of ferric iron results in metabolic acidosis.
Inhibits mitochondrial function leading to hepatic damage, hypoglycaemia,
and hypoprothrombinaemia.
Inhibits thrombin-induced conversion of fibrinogen into fibrin.
Has a direct corrosive action on the GI mucosa.

20. CLINICAL FEATURES
Stage I (0.5 to 2 hours)
Stage II (recovery- false security)
Stage III (2 to 12 hours after Stage I)
Stage IV (2 to 4 days)
Stage V (days to weeks)
DIAGNOSIS
1. x-ray
2. Serum iron level
3. Total leucocyte count (TLC)
4. Chelation challenge test
5. Qualitative desferrioxamine colour test (QDCT)

21. TREATMENT
1. Stomach wash
2. Magnesium hydroxide solution (1%)
3. Correction of hypovolaemia, and metabolic acidosis.
4. Chelation therapy:
Chelation can be done either with desferrioxamine (parenteral) or deferiprone
(oral).

22. Mercury
PHYSICAL APPEARANCE
heavy, silvery liquid
USUAL FATAL DOSE
The amount of ingested mercury that would be fatal to a man is estimated at 100
grams.
Mercuric chloride: 0.5 to 1 gm/70 kg
Mercurous chloride : 1.5 to 2 gm/70 kg
TOXICOKINETICS
Inhalation  elemental Hg absorbed through alveolar membrane  enters blood
stream  converted to mercuric ions(Hg2+)  renal tubular damage during
excretion.

23. CLINICAL FEATURES
Inhalation:
Tremor:
Ataxia, reeling gait.
A Parkinsonian syndrome
Metallic taste
Gingivitis, halitosis
Erythematous macular or papular rashes
Erethism:
Mercuria lentis:
Renal damage
Ingestion:
- Colitis.
- Melanosis coli.
- Dementia.
- Tremor.
- Renal failure.
- Acrodynia (Pink disease)

24. DIAGNOSIS
1. x-ray.
2. Blood mercury level
3. Urine mercury level
4. Hair analysis
TREATMENT
1. Chelation therapy—
– BAL (British Anti Lewisite)
- 100 mg by deep IM, every 4 hours for 48 hours, followed by 100 mg every 8
hours for 8 to 10 days.
OR
– DMPS ( 2,3 DiMercapto Propane-1-Sulfonate)
- 5 mg/kg IV, or 6 infusions of 250 mg/day, followed by 100 mg orally twice a day
for 24 days.
OR
– DMSA (Meso 2,3 DiMercapto Succinic Acid, or Succimer)
- 30 mg/kg/day orally for 5 days, followed by 20 mg/day for 14 days.

25. OR
– D-Penicillamine
- 250 mg qid, for adults, (20 mg/kg/day) for 5 to 10 days.
2. Supportive measures.

26. THANK YOU!