A Brief introduction about Heavy Metals Toxicity to medical students. The lecture covers the mechanism of toxicity for these compounds and the common clinical presentation associated with acute and chronic exposure.

1. Toxicity by Heavy Metals
Dr. Maha Farid,
MBBCh, MS, PhD.
Dept. Of Forensic Medicine and Clinical Toxicology
Faculty of Medicine
Helwan University
Hg
PbCdAs Fe
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 1

2. Objectives
■ Recognize the common characteristics of heavy metal toxicity.
■ Understand the mechanism underlying the toxicity by heavy metals.
■ Distinguish the sources of exposure to heavy metals in the environment.
■ Identify the clinical presentations caused by exposure to toxic doses of heavy
metals.
■ Acknowledge the main outlines of managing patients exposed to toxic doses
of heavy metals.
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 2

3. Case Study
45 years old male patient presented to the ER with severe vomiting and diarrhea. No fever and no
history of any chronic debilitating disease.
History: The patient mentioned that his symptoms started several hours ago, no history of other family
members suffering from similar condition.
Physical examination: The patient looks restless and in pain. Temp is 36.8º C, Pulse is 110/min, BB is
90/50 mmHg, and RR is 28/min. disturbed mental status
Lab work: Elevated liver enzymes, high levels of urea and creatinine, disturbed electrolyte level and
normal CBP.
Differential Diagnosis:
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 3
Management: Stabilization of the patient by starting an IV line to prevent dehydration. U/S was
performed and showed normal abdominal sonography.

4. Heavy Metals
■ Surrounded by heavy metals every where.
■ They are heavy atomic weight or high-density (5 g/cm3) metallic elements.
■ They are toxic at low concentrations.
■ Examples are:
– Arsenic: herbicides and insecticides.
– Mercury: contaminated fish and seafood.
– Lead: battery industry, smelters, pottery, old paints and pigments
– Iron: iron containing medications.
– Cadmium: paints and cigarette smoking.
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 4

5. 12/27/2019 Toxicity by Heavy Metals_MF, PhD. 5
Int. J. Environ. Res. Public Health 2019, 16(22), 4446;

6. Common Characteristics of Toxicity
■ Double action
 Local: irritation of the GIT mucosa/respiratory epithelium.
 Remote: Parenchymatous organs such as liver, kidneys and heart.
■ Symptoms and signs appear after a latent period following exposure.
■ Cumulative toxic effect: acute and chronic forms of toxicity.
■ Great affinity to keratin tissues.
■ Resistant to putrefaction in post-mortem examination.
■ Causes peripheral neuritis (sensory, motor or both).
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 6

7. Common Characteristics of Toxicity (cont.)
■ Biotransformation:
– Renal excretion.
– Gastrointestinal re-excretion.
– Affect the (-SH) in enzymes of oxidation/reduction → General protoplasmic poisons.
■ Management:
– Stomach wash.
– General antidotes: Sodium thiosulfate, tannin, charcoal.
– Specific antidotes: Chelating agents (DMSA, EDTA, BAL, Penicillamine).
■ Detection:
– Atomic Absorption Spectrometry.
– Reinsch’s Test: Soluble Inorganic salts of mercury, arsenic and antimony.
– Marsh’s Test: Organic compounds of arsenic and antimony.
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 7

8. Mechanism of Action:
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 8
Pb2+ Cell
enzyme
SH
SH
SH
SH
ROS
O2
H2O ↑ ROS
Apoptosis
Cell damage

9. Chelation Therapy
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 9
Pb2+ Cell
enzyme
SH
SH
SH
SH
ROS
O2
H2O ↑ ROS
Apoptosis
Cell damage
Chelator
SH
SH

10. 12/27/2019 Toxicity by Heavy Metals_MF, PhD. 10
M., Oves & Khan, Mohammad & Zaidi, Almas & Ahmad, Ees. (2012). Soil Contamination, Nutritive Value, and Human Health Risk Assessment of Heavy Metals: An Overview. 10.1007/978-3-
7091-0730-0_1.
Heavy Metals Cycle in the Environment

11. Occupations associated with HMT
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 11

12. Industries associated with HMT
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 12

13. Mode of Toxicity
■ Accidental
– Very common in the environment.
– Occupational toxicity.
– Cumulative effect.
■ Suicidal
– Easy access (Pesticides, environmental products).
– Cheap and flavorless.
■ Homicidal
– Long latent period.
– Odorless and flavorless.
– Different colors: (mixed with different kinds of food).
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 13

14. Arsenic Toxicity
■ Acute Toxicity:
– Large dose ex. Homicidal or suicidal.
■ Chronic Toxicity:
– Small repetitive doses ex. Occupational exposure.
Mechanism of Action:
• Local: Irritation of epithelium or mucosa depending on the route of exposure.
• Remote: Affects the parenchymatous organs and skin.
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 14

15. Arsenic Salts
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 15
Kwan, Stanley S.K.. “The role of ASK1 in arsenic trioxide-induced cell death.” (2013).

16. Manifestations of Arsenic Toxicity
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 16
Muhammad Shahid, Camille Dumat, Nabeel Khan Niazi, Sana Khalid et Natasha, « Global scale arsenic pollution : increase the scientific knowledge to reduce human exposure », Vertigo - la revue électronique
en sciences de l'environnement [En ligne], Hors-série 31 | septembre 2018.

17. Dermatopathology of Chronic Arsenic Toxicity
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 17
Hossain K., Hasibuzzaman M.M., Himeno S. (2019) Characteristics and Health Effects of Arsenic Exposure in Bangladesh. In: Yamauchi H., Sun G. (eds) Arsenic Contamination in Asia.
Current Topics in Environmental Health and Preventive Medicine. Springer, Singapore.
(a) Palms and fingers: Punctate and
diffuse keratosis.
(b) Palms and fingers: Punctate
keratosis on right hand and
Bowen’s carcinoma on the left
hand.
(c) Dorsum of foot: Diffuse and
punctate pigmentation.
(d) Sole: Severe punctate keratosis.
(e) Chest: Diffuse pigmentation and
punctate leukoderma.
(f) Forehead: Multiple Bowen’s
disease.

18. Dermatopathology of Chronic Arsenic Toxicity
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 18
Bagic, Anto & Lupu, V & Kessler, C & Tornatore, Carlo. (2006). Iatrogenic arsenic induced Mees' lines. Postgraduate medical journal. 82. 515. 10.1136/pgmj.2006.045229.
Heavy Metal Poisoning: Clinical Presentations and Pathophysiology - Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/Arsenic-poisoning-and-
Mees-lines-Courtesy-of-R-Pascuzzi-MD-Indianapolis-IN_fig1_7212503.
Iatrogenic induced Mees’ lines following cancer
chemotherapy with Arsenic trioxide.
Chronic Arsenic poisoning causing Mees’ lines in the nail.

19. Mercury Toxicity
■ Mode of Toxicity:
– Accidental:
• Acute: irritation and severe pain.
• Chronic: CNS presentation.
■ Compounds:
– Organic salts: pesticides, embalming → Seafood (NOT for pregnant women and infants).
– Inorganic salts: cosmetics, disinfectants, explosive devices.
– Metallic Mercury: dental amalgam, thermometers, vapor lamps.
■ Mechanism of Action
– Local: Irritation of epithelium or mucosa (contact dermatitis, corrosive like action).
– Remote: Affects the parenchymatous organs (liver and kidneys) and CNS.
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 19

20. Metallic Mercury
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 20
Thermometers
Dental fillings (amalgam)

21. Methylmercury
■ Easy Absorption.
■ Bioaccumulation.
■ Biomagnification.
■ 1950s, Minamata Japan.
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 21
https://www.sfei.org/calendar_events/4326#sthash.NfPZjZGN.dpbs

22. Ethyl mercury (Thimerosal)
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 22
https://www.cdc.gov/vaccinesafety/concerns/thimerosal/index.html

23. Manifestations of Mercury Toxicity
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 23
https://www.alignable.com/oroville-ca/forum/do-you-know-what-heavy-metals-are-and-how-to-remove-them-from-our

24. Manifestations of Hg
Toxicity
Pink Disease:
■ Common in Children.
■ Hypersensitivity or idiosyncrasy .
■ Acrodynia: swollen, erythematous and desquamated skin of
the extremities associated with paresthesia.
■ Other manifestations: irritability, excessive salivation,
tachycardia and hypertension.
■ Differential Diagnosis: Kawasaki Disease.
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 24
Pink ladies: mercury poisoning in twin girls
Michael Weinstein, Stacey Bernstein
CMAJ Jan 2003, 168 (2) 201;

25. Manifestations of Hg
Toxicity
Mercurial Erethism:
Mental disorder with behavioral patterns:
– Mood changes.
– Irritability.
– Shyness and not wanting to work under observation.
– Depression.
– Explosive anger episode alternating with apathy.
– Loss of memory.
– Insomnia and sleep disorders.
Toxicity by Heavy Metals_MF, PhD. 12/27/2019 25

26. Manifestations of Hg
Toxicity
Mercury Gingivitis:
– Mercury re-excreted in saliva.
– Excessive salivation.
– Swollen painful bleeding gums.
– Grey linear pigmentation of the gums.
– Loss of teeth.
Toxicity by Heavy Metals_MF, PhD. 12/27/2019 26

27. Lead Toxicity
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 27
Inorganic:
• Metallic lead:
o Alloys with other metals such as copper and tin.
o Used in battery manufacturing and electronics.
o Very toxic in both gas and solid forms.
• Lead salts:
o Oxides soluble in water containing ammonia and weak acids.
o Used in paints and pigments: colored substances.
Organic Lead:
o Gasoline: tetra-ethyl lead increases fuel efficiency.
o Insecticides: lead arsenate.
o Medical remedies: Lead acetate or subacetate (ecbolic).

28. Lead Toxicity
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 28
Mechanism of Action
• Local: Irritation of epithelium, mucosa or skin.
• Remote: Affects the parenchymatous organs (liver and kidneys), CNS and bones.
Routes of Toxicity
• Oral : Most common, soluble lead compounds ex. Lead subacetate.
• Inhalation: Lead fumes.
• Contact: Tetra-ethyl lead only absorbed through the skin.
• Tissue Absorption: Following unremoved retained lead bullets or shots in the body.

29. Lead Toxicity
Distribution in the body
• Follows the Ca2+ metabolism in the body.
• Stored in the epiphysis of long bones.
• Deposition of lead into the bones:
 Alkalis, Vit D and Ca2+ rich diet.
• Mobilization of lead from the bones:
 Ammonium Chloride, iodides and PTH.
Toxicity by Heavy Metals_MF, PhD. 12/27/2019 29

30. Lead Toxicity
Acute Lead poisoning :
■ Overdose:
• lead-containing traditional medical
remedies .
• large amounts of lead salts.
■ Sudden de-leading.
■ Exposure to contaminated air with lead.
Chronic Lead poisoning:
■ Household exposure
■ Industrial exposure
■ Absorption from retained shots or bullets.
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 30

31. Manifestations of Lead Toxicity
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 31
https://chewingthesfat.com/flinth2o/leadpoisoning.html

32. Complications of Chronic Lead Poisoning
Plumbism
■ Mental Retardation in young children.
■ Peripheral Neuritis: mainly motor, affect extensor muscles.
■ Demyelination of axis cylinders of the peripheral nerves.
■ Wrist Drop and/or ankle drop.
■ Optic Nerve Atrophy.
■ Burton’s line: Blue-purplish line in the gums around the teeth.
■ Reaction between lead and Sulphur ions produced by the oral bacteria.
■ Anemia: Basophilic stippling of the red blood cells.
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 32

33. 12/27/2019 Toxicity by Heavy Metals_MF, PhD. 33

34. 12/27/2019 Toxicity by Heavy Metals_MF, PhD. 34
Helmich F, Lock G N Engl J Med. 2018 Nov 8;379(19):e35. doi:
10.1056/NEJMicm1801693.
Warang, P., Colah, R.B., & Kedar, P.S. (2017). Lead Poisoning Induced Severe Hemolytic Anemia, Basophilic
Stippling,Mimicking Erythrocyte Pyrimidine 5'-nucleotidase Deficiency in BetaThalassemia Minor.

35. Iron Toxicity
■ Most commonly accidental toxicity.
■ In children → large doses of iron pills (mistaken for
candy).
■ Fatal iron poisoning > fatal aspirin poisoning.
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 35

36. Iron Toxicity
■ Mechanism of Action:
• Local:
• Corrosive effect on the GIT mucosa → coagulative necrosis.
• Cause of death: bleeding and shock.
• Remote:
• Increase capillary permeability → loss of plasma → ↓ blood volume → hypovolemic
shock.
• Cellular Hypoxia → Acidosis.
• Hepatotoxicity: direct toxic effect on the mitochondria of the liver.
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 36

37. Phases of Acute Iron Toxicity
■ Stage I: Local GIT manifestations (1/2- 6hrs).
 Corrosive effects on stomach and duodenum → bloody diarrheal, hematemesis.
■ Stage II: Quiescent stage (6- 24hrs).
 Apparent recovery: compensation of the GIT manifestations.
■ Stage III: Systematic Toxicity (12- 24hrs).
 Hypovolemia and Acidosis → pallor, cold extremities, tachycardia and tachypnea and hypotension.
 Direct toxic effect of iron on the cardiac muscles.
■ Stage IV: Hepatic Necrosis (24-48hs).
 Portal blood delivers high level of iron to the liver → hepatic necrosis and metabolic acidosis.
 Disturbed coagulation mechanisms and inhibition of clotting factors.
■ Stage V: Intestinal obstructions (4-6wks).
 Due to pyloric stenosis and gastric fibrosis.
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 37

38. Management
(5S)
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 38
Stabilization Of
The Patient
Symptomatic
Treatment
Stomach Wash Specific Antidote
Chelation Therapy
Stop Further
Exposure

39. Chelation Therapy
■ Iron → Defroxamine.
■ Lead → E.D.T.A.(Ethylene Diamine Tetra-acetic Acid).
D.M.S.A (DiMercapto Succinic Acid).
■ Mercury → B.A.L(British Anti Lewisite).
Penicillamine.
D.M.S.A.
■ Arsenic → B.A.L(British Anti Lewisite).
Penicillamine.
D.M.S.A.
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 39

40. Self Learning Topics
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 40
ARSINE GAS TOXICITY.
CADMIUM TOXICITY

41. References
■ Olivier Pourret, Andrew Hursthouse, Int. J. Environ. Res. Public Health 2019, 16(22), 4446.
■ M., Oves & Khan, Mohammad & Zaidi, Almas & Ahmad, Ees. (2012). Soil Contamination, Nutritive
Value, and Human Health Risk Assessment of Heavy Metals: An Overview. 10.1007/978-3-7091-0730-
0_1.
■ Muhammad Shahid, Camille Dumat, Nabeel Khan Niazi, Sana Khalid et Natasha, « Global scale arsenic
pollution : increase the scientific knowledge to reduce human exposure », VertigO - la revue
électronique en sciences de l'environnement [En ligne], Hors-série 31 | septembre 2018.
■ Kwan, Stanley S.K. “The role of ASK1 in arsenic trioxide-induced cell death.” (2013).
■ Hossain K., Hasibuzzaman M.M., Himeno S. (2019) Characteristics and Health Effects of Arsenic
Exposure in Bangladesh. In: Yamauchi H., Sun G. (eds) Arsenic Contamination in Asia. Current Topics in
Environmental Health and Preventive Medicine. Springer, Singapore.
■ Heavy Metal Poisoning: Clinical Presentations and Pathophysiology - Scientific Figure on ResearchGate.
Available from: https://www.researchgate.net/figure/Arsenic-poisoning-and-Mees-lines-Courtesy-of-R-
Pascuzzi-MD-Indianapolis-IN_fig1_7212503.
■ https://www.cdc.gov/vaccinesafety/concerns/thimerosal/index.html
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 41

42. References
■ https://www.sfei.org/calendar_events/4326#sthash.NfPZjZGN.dpbs
■ https://www.alignable.com/oroville-ca/forum/do-you-know-what-heavy-metals-are-and-how-to-remove-them-
from-our
■ Michael Weinstein, Stacey Bernstein, Pink ladies: mercury poisoning in twin girls, CMAJ Jan 2003, 168 (2)
201;
■ https://chewingthesfat.com/flinth2o/leadpoisoning.html
■ Suraj Chandrasekar, MD; Laurie M. Lomasney, MD; Nathan Derhammer, MD, Systemic Lead Toxicity
,Orthopedics. 2015;38(10):592, 644-64
■ Olivier Pourret, Andrew Hursthouse, Int. J. Environ. Res. Public Health 2019, 16(22), 4446.
■ Helmich F, Lock G N Engl J Med. 2018 Nov 8;379(19):e35. doi: 10.1056/NEJMicm1801693.
■ Warang, P., Colah, R.B., & Kedar, P.S. (2017). Lead Poisoning Induced Severe Hemolytic Anemia, Basophilic
Stippling,Mimicking Erythrocyte Pyrimidine 5'-nucleotidase Deficiency in BetaThalassemia Minor.
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 42

43. Case Study
45 years old male patient presented to the ER with severe vomiting and diarrhea. No fever and no
history of any chronic debilitating disease.
History: The patient mentioned that his symptoms started several hours ago, no history of other family
members suffering from similar condition.
Physical examination: The patient looks restless and in pain. Temp is 36.8º C, Pulse is 110/min, BB is
90/50 mmHg, and RR is 28/min. disturbed mental status
Lab work: Elevated liver enzymes, high levels of urea and creatinine, disturbed electrolyte level and
normal CBP.
Differential Diagnosis: Acute Arsenic Poisoning, Gastroenteritis, Cholera.
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 43
Management: Stabilization of the patient by starting an IV line to prevent dehydration. U/S was
performed and showed normal abdominal sonography.

44. Take Home message
12/27/2019 Toxicity by Heavy Metals_MF, PhD. 44
spreadshirt.com
Contact:
drmahafarid@gmail.com
https://www.linkedin.com/in/maha-farid-
44615025/