Heavy metal and human health

DESCRIBED ABOUT TOXICITY IN HUMAN DUE TO HEAVY METAL BRIEFLY

1. Heavy metal and human health

2. Background Those metals with a specific gravity of greater than 4.0 . Mainly produced from industrial activities most hazardous heavy metals are- arsenic (As) lead ( Pb ) mercury (Hg) cadmium ( Cd )

3. Factors affecting toxicity The total dose absorbed The exposure either acute or chronic. age of the person e.g.-Young children are more susceptible to lead toxicity as compared with adults

4. 4- The route of exposure E.g.- Elemental mercury is inert in the gastrointestinal tract and through intact skin, but inhaled or injected elemental mercury have disastrous effects.

5. LEAD TOXICITY

6. 2nd most hazardous substance lead poisoning is the most important chronic environmental illness affecting modern children.

7. Mode of Exposure In the environment lead is in organic and inorganic compounds. Inorganic lead compounds are less toxic Poisoning is either by direct ingestion of lead compounds or items contaminated with them.

8. Occupational exposure Battery makers Cable makers Glass makers/polishers Gunshot/gun barrel makers Jewelers Lead burners Painters Pigment makers Pipe cutters Printers Non-occupational exposure Battery burning Bullet retention Cooking in leaden pots Target shooting lead containing herbal medicines Ingestion of paints still used as additives in gasoline in several countries Exists in cigarette smoke. surface paints on the toys. stagnant water in pipes.

9. Absorption GI Tract Children are at greater risk for lead absorption(Adults:11%-16%, Children : 40% - 50%) Increased with Fe, Ca, Zn deficiency decreased if phosphorus, riboflavin, vitamin C, and vitamin E are in the diet.

10. Absorption 2 . Lungs 50% - 70% if < 1 μm 3. Skin Inorganic lead is non-absorbable Organic lead is readily absorbed

11. Distribution Exchanged in 3 compartments: Blood Soft tissue (liver, kidneys, lungs, brain, spleen, muscles, and heart) Mineralizing tissues (bones and teeth). In bone it is stored for several years. Redistribution occurs in pregnancy

12. crosses the placenta exists in breast milk . malnutrition and iron deficiency-higher lead absorption in the mother.

13. Pathophysiology Lead inhibit enzyme with sulfhydryl groups Delta amino levulinic acid dehydratase (formation of porphyrin ring) and ferrochelatase (incorporation of iron into porphyrin ring ) inhibited, decrease in heme production Basophilic stippling of erythrocytes

14. Pb 2+ disturbs intracellular Ca 2+ homeostasis ( calmodulin , protein kinase C, Ca 2+ -dependent K + channels and neurotransmitter release disturbed) brain delayed or reversed development permanent learning disabilities seizures, coma, death .

15. child’s developing brain is highly susceptible ( cerebellar hemorrhage, increased blood-brain barrier permeability, and edema.) decreased fertility, and increased miscarriage. The Burton line or gingival lead line is a dark blue line along the gums

16. Symptoms Acute toxicity- Abdominal pain ,vomiting, constipation, headache, ataxia, somnolence, seizures lead nephropathy elevated intracranial pressure (ICP)- lead encephalopathy .

17. Chronic toxicity ( plumbism ) low-level exposure over a long time Early symptoms- Diffuse muscle weakness, and p aresthesias confusion/ irritability - Unusual metallic taste in mouth

18. Late complication- diminished libido anemia p eripheral neuropathy in extensor surfaces k/a wrist drop and/or foot drop (most common in adults)

19. In children- permanent learning disability and behavior disorders. hearing loss, aggression delayed growth.

20. Burton line Wrist drop

21. DIAGNOSIS blood lead level (BLL)(> 9  μg / dL ) CBC - basophilic stippling of red RBCs,anemia ( microcytic,hypochochromic ) lead in bones ( X-ray fluorescence, XRF ) Acute poisoning- Radiographic examination of the abdomen

22. Free erythrocyte protoporphyrin level ( FEP )(distinguish recent acute lead exposure from chronic exposure) High blood lead lead FEP normal- acute Both are high- chronic

23. Treatment Succimer (oral chelating agent @ 45 µg/ dL ) Edetate calcium disodium ( CaNa 2 EDTA ) is a parenteral chelating agent. (does not cross the blood-brain barrier) dimercaprol should be administered first. (cross the blood-brain barrier) So both are used together

24. MERCURY TOXICITY

25. Sources 3rd on the Top Hazardous Substances. Naturally- degassing of the earth's crust and volcanic eruption. mining, smelting, and industrial discharges Atmospheric mercury comes to the earth in rainfall, accumulating in soil and food chains and fish in lakes .

26. Paint,fungicide (old paint still exist). Thermometers, thermostats, fluorescent light bulbs, amalgams Antiseptics ( mercurochrome and merthiolate ), Vaccines (flu vaccines contain thiomersal )

27. Mode of Exposure three forms Elemental Inhalation(main source) Poorly through GI tract Skin contact also Inorganic Poorly absorbed in GI tract(7-15%). Dermal exposure causes toxicity Organic Lipid soluble well absorbed via GI (90-100%); lungs and skin Cross BBB and affects CNS Can cross placenta and into breast mi lk

28. Pathophysiology Binds to sulfhydryl of enzymes (cellular stress response, protein repair, and oxidative damage prevention.) Methylmercury inactivates Na+/K+- ATPase (membrane depolarization eventual cell death)

29. Industrial mercury- inorganic form aquatic organisms and vegetation convert it to methylmercury . Then mercury becomes biomagnified in the fish . (Fish protein binds about 90% of the consumed methyl mercury ) Even by cooking it cannot be removed

30. Minamata disease-( Minamata Bay ) After eating methyl mercury containing fish neurologic damage such as visual loss, extremity numbness, hearing loss, and ataxia Babies exposed in utero and also exposed after birth through breast milk

31. Elemental Mercury Acute- Acute necrotizing bronchitis(vapor inhalation) Pneumonitis Skin, and nose irritation

32. Long term exposure affects CNS. Early : insomnia, impaired memory, mild tremor Late : progressive tremor and erethism (red palms , emotional lability (irritability and nervousness), renal toxicity ( proteinuria , or nephrotic syndrome)

33. Mercurial erethism

34. Inorganic Mercury Gastrointestinal ulceration and hemorrhage proximal tubular necrosis and anurea Acrodynia ( Pink disease , erythroedema , or Feer’s disease ) in dermal exposure maculopapular rash(fingertips, toes ) pus-filled skin eruptions swollen and painful extremities peripheral neuropathy hypertension, renal tubular dysfunction.

35. Acrodynia / Pink disease

36. Organic Mercury Methylmercury , dimethylmercury and ethylmercury effects the CNS ( Minamata disease ) Teratogen with large chronic exposure Asymptomatic mother Infants with mental retardation, blindness, deafness, and seizures ( congenital Manimata disease ).

37. Diagnosis History of exposure Elemental and inorganic mercury-urine collection organic mercury- whole-blood ( s’d be < 6  μg /L) Hair analysis is more reliable

38. Treatment Gastric lavage (organic mercury) Activated charcoal(Both) Whole bowel irrigation Hemodialysis (with L- cysteine ) is used in renal damage Neostigmine for methylmercury toxicity (acetylcholine deficiency)

39. Chelating therapy-DMSA(organic mercury, mercury vapor poisoning),or BAL(inorganic mercury). Pregnant women and nursing mothers should avoid consuming larger fish(mercury concentrations is higher in larger fish)

40. Arsenic toxicity

41. Source Most common cause of acute heavy metal poisoning in adults Number 1 on the top hazardous substances. Smelting process of copper, zinc, and lead Manufacturing of chemicals, galvanization Manufacturing of pesticides that contain arsenic. (Arsine gas ) Paints, pesticides (herbicides, insecticides, fungicides, rodenticides , wood preservatives) Tobacco smoke

42. Mode of Exposure Three forms, organic and inorganic arsenic compounds, arsine gas. Organic arsenic is 500 times less harmful than inorganic arsenic. Organic arsenic exposure mostly by eating seafood . Inorganic arsenic, reduced (trivalent as (iii)) and oxidized ( pentavalent as(v)) Inorganic arsenic poisoning through mining and smelting and dissolved solids in ground water and soil.

43. Toxicocokinetics Inorganic arsenic are readily absorbed through the GI tract After the absorption it accumulate in tissues and body fluids. also readily deposited in the hair and nails In the liver, the metabolism of arsenic(organic)

44. Pharmacokinetics A . Pentoxide trioxide increases its toxicity and bioavailability B. Trioxide ( monomethylarsonous acid (MMA(III), dimethylarsinous acid (DMA(III)) Methylation decreases toxicity and increases excretion trioxide GSH MMA(III)+ DMA(III) Arsenate methyl transferase liver

45. Mechanism of action As +3 : SH- containing enzymes inhibit of their activity ( like glutathione reductase and thioredoxin reductase ) Inhibit the Krebs cycle (inhibit pyruvate dehydrogenase ) and oxidative phosporylation . inhibits cellular glucose uptake, gluconeogenesis , fatty acid oxidation

46. As +5 Replace the phosphate ester bond in ATP (arsenic ester stable bond ) High carcinogenic(inhibition of DNA repair due to interaction of arsenic with –SH group ) Irritant effect Endothelial damage, loss of capillary integrity

47. Arsenic trioxide- Prolongation of cardiac action potential duration Induce atherosclerosis Platelet aggregation Reducing fibrinolysis

48. Symptoms of toxicity Acute toxicity: H ematemesis , abdominal pain, muscle cramps, Diarrhea ( rice-water stool) Garlic-like breath Thirst and metalic taste Contact dermatitis in direct tactile contact with arsenic compounds. Arsine gas exposure- acute hemolytic anemia and striking chills .

49. Chronic toxicity: Multiple organ dysfunctions problems Neuronal :peripheral neuropathy, encephalopathy, dementia, cognitive impairment, hearing loss CVS : hypertension, myocardial infarction, anemia and leukopenia Respiratory : pharyngitits , laryngitis GIT : severe abrominal cramping and hematemesis .

50. kidney and liver damage Skin abnormalities : darkening of the skin appearance of small " corns " or " wart " on the palms, soles ( palmar keratosis ). whitish lines ( Mees lines ) found on the fingernails.

51. Mees line Palmar keratosis

52. Reproductive system : spontaneous abortion lower birth weights Carcinogenic : cancers of the skin, liver, respiratory tract, kidney, bladder and gastrointestinal tract

53. Diagnosis laboratory analysis of urinary whole blood arsenic measurments arsenic contents in hair and fingernails Normal values Spot urine= ~11 mcg/L Whole blood= <1mcg/L (usually is elevated in acute intoxication) Acute hemolytic anemia in arsine exposure

54. Treatment Hemodynamic stabilization and electrolytes solutions Blood transfusion in acute blood loss Acute arsenic ingestions- orogastric lavage Whole bowel irrigation with polyethylene glycol Dimercaprol , and succimare for chelation

55. Cadmium

56. Sources soils and rocks coal and mineral fertilizers batteries, Pigments metal coatings Plastics electroplating. Tobacco smoking largest source

57. leaves, fruits and seeds. accumulates in animal milk and fatty tissues Seafood, such as molluscs and crustaceans

58. Toxicity Human carcinogens. Lungs damage occur through breathing high levels of cadmium. Acute - Ingesting very high levels Vomiting and diarrhoea. Severe respiratory irritation

59. Chronic - Kidneys damage mostly PCT(increased excretion of α 2, β 2, gamma globulins) Later aminoaciduria, phosphaturia and glucosuria Lung damage(occupational exposure) Fragile bones(loss of ca in urine ) Testicular degeneration Risk factor for prostate cance r .

60. itai-itai disease syndrome- severe renal dysfunction damage to bone structure. elderly multiparous women mostly affected poor nutritional status, who had lived in the contaminated area for many years.

61. Itai itai disease

62. Barium Source - Barium-nickel -spark-plug electrodes Vacuum tubes Oxygen-removing agent Barium sulfide - fluorescent lamps Barium sulfate -diagnostic medicine Drilling muds , paint, bricks, ceramics, glass, and rubber.

63. Health effects ● Short term exposure- vomiting, abdominal cramps, diarrhoea, difficulties in breathing, increased or decreased blood pressure, muscle weakness. ● Large amounts - high blood pressure, changes in heart rhythm or paralysis, kidney damage, respiratory failure and possibly death. barium carbonate or chloride- hypokalemia (adverse effect on heart)

64. Chromium Source Persistent in sediments in water Stainless steel Electroplating, magnetic tapes Pigments for paints, cement, paper, rubber, composition . Wood preservatives.

65. Health effects Chromium (VI) is human carcinogens ● Breathing - irritation to nose; nose ulcers; runny nose ,asthma ● Skin contact- skin ulcers, Allergic reactions ● Long term exposure- damage to liver, kidney ,circulatory and nerve tissues chromium(III) in high conc. can lead to  DNA damage Haemolysis

66. Selenium Rocks and soils Electronics industry Glass industry , plastics, paints, enamels, inks, and rubber Pharmaceuticals, nutritional feed additive for poultry and livestock Pesticide formulations Antidandruff shampoos Fungicides Radioactive selenium- diagnostic medicine.

67. Health effects Upper Intake Level is 400 µg/day . ● Short-term oral exposure -nausea, vomiting, and diarrhea . ● Chronic oral exposure-produce selenosis .(hair loss, nail brittleness, neurological abnormalities. ) ● Brief aerosol exposures -irritation, bronchitis, difficulty breathing Longer-term exposure -respiratory irritation, bronchial spasms

68. Silver Jewelry , silverware, Electronic equipment Dental filling Brazing alloys and solders Mirrors Photographic film Disinfectants and antibacterial agent.

69. Health effects Exposure to high levels for a long period - argyria (blue-gray discoloration of the skin and other body tissues) Aerosol exposure-breathing problems, lung and throat irritation, and stomach pains. ● Skin contact with-mild allergic reactions

70. argyria