Heavy metals -toxicity

• Heavy Metals


  • Arsenic
  • Cadmium
  • Lead
  • Mercury
• General Mechanism of Action of Heavy Metals

  1. Bind to sulphydryl groups of proteins such as enzymes and membrane proteins

  2. Oxidise the SH groups to Disulphide

  3. Disrupt the structure and function of these important proteins

  4. Lead to cell damage and death eg haemolysis
• Synthetic antidotes


  Chelating agents eg Dimercaprol, EDTA, Penicillamine
• Arsenic


  • One of the most toxic metals on earth
  • Forms: Trivalent, Pentavalent
  • Routes of Exposure: Ingestion, Inhalation
• Arsenic Health Effects


  • Fever, anorexia, liver enlargement, death
  • Neurotixicity of PNS and CNS, liver damage, gangrene of lower limbs
  • Skin cancer, lung cancer
  • Dermatitis, darkening of the skin, leukemia, kidney, and bladder cancers
• Cadmium


  • Largely used in batteries and pigments especially in plastic products
  • Other uses: Lowest melting alloys, Electroplating, As a barrier to control nuclear fission, Semi-conductors used for light detection or solar cells, In PVC stabilizers, Used to block voltage-dependent calcium channels from fluxing calcium ions
• Cadmium Toxicity


  • This kind of toxicity is due to an occupation
  • Those that are affected – industrial workers involved in the processes of metal plating, nickel-cadmium battery production, pigments, plastics and other synthetics
  • Human exposures to environmental Cd are primarily the result of fossil fuel burning and municipal wastes
  • Cd usually accumulates in the kidney, the primary organ where at high levels past the critical threshold – kidney failure
• Other Cadmium Exposures


  • Food
  • Cigarette smoke (the main source of contamination in the general population)
  • Urban atmospheric air (levels may be high in the vicinity of cadmium producing facilities)
  • Lichen and moss (these concentrate cadmium and other heavy metals)
• Notable instances of Cadmium toxicity


  • Long term exposure to Cd traces in food and water
  • Decades following WWII – (Japan) mining operations contaminated the Jinzu river with Cd and other trace metals causing the Cd accumulating in rice crops growing along the bank
• Illnesses caused by Cd exposure

  • Inhalation – metal fume fever which progresses into chemical pneumonitis, pulmonary oedema and death
  • Consumption – Itai-itai disease (Japan) and renal abnormalities such as proteinuria and glucosuria
  • Cd and Cd containing compounds are carcinogenic
  • Both acute and chronic intoxication due to Cd exposure in humans and animals
• Acute Cadmium Toxicity


  • Metal fume fever (has flu like symptoms)
  • Acute pulmonary oedema – develops within 24hrs
  • Death by asphyxia – if it does not occur within a week, the symptoms are resolved
• Chronic Cadmium Toxicity


  • The most serious consequence is cancer (prostate and lung)
  • 1st observed chronic effect is generally kidney damage manifested by high levels of low molecular weight protein being excreted in urine
  • Cd is also believed to cause pulmonary emphysema and bone disease – osteoporosis and osteomalacia
  • It may also cause anaemia, teeth discolouration by cadmium sulfide and loss of smell (anosmia)
  • Rhinitis, occasional ulceration of the nasal septum and damage to the olfactory nerve
• Tobacco Smoke


  • This is the single most important source of Cd in the general populous
  • It is estimated that 10% of the Cd content of a cigrette is inhaled through smoking
  • 50% of the cadmium inhaled is absorbed through the lungs. Absorption through the lungs is much more effective than absorption from the gut
• Cadmium Prevention


  • The best prevention is avoidance
  • In case one is a worker in the industry that used cadmium products ensure to wear protective gear: Dust masks, Local ventilation of the work area where the aspired are is vented outside
  • Investigate the area for run-off water that come from factories and farms are in close proximity to these – steps can be made to prevent the runoff of cadmium waste that may lead to the ingestion and poisoning
• Cadmium Exposure


  • ~7% of renal dysfunction in the general population is caused by cadmium exposure
  • The kidney is the primary target for Cd toxicity
  • Cell death in the renal tubular epithelium cells is due to apoptosis
• Cadmium Treatment


  • Calcium EDTA is used in the acute treatment of acute intoxication
  • Care must be taken when using this in the presence of renal impairment
  • Chronic intoxication treatment does not have a chelating agent
• The greatest concentrations of cadmium found in Jamaica is found in the central regions where bauxite is present – Manchester and St. Elizabeth
• There are only hints remaining of possible health effects due to Cd intoxication to date in Jamaica
• The incidence of end renal disease in Jamaica at that time was significantly higher than that in Latin American countries like Costa Rica, Puerto Rico and the Dominican Republic
• Lead


  • Used in manufacture of batteries, plastics, china, ceramic glass, and paint products
  • Routes of exposure: Ingestion of lead-contaminated glaze in pottery, paint chips, dust in older homes
  • Deficiencies in nutrients can enhance lead absorption
• Lead Absorption


  • Gastrointestinal: Adults absorb 5-15%, retain about 5% of absorbed dose
  • Children absorb about 40% and retain about 32% of absorbed dose
  • Pulmonary: About 90% of Pb particles in outdoor air are small enough to enter the alveoli
• Lead Distribution


  • Blood Pb: More than 90% of Pb in blood is in the red blood cells. Blood Pb concentrations are used to measure recent exposure to Pb
  • Bone - Largest and kinetically the slowest pool, t1/2 = >20 yr. Contributes to maintaining blood Pb levels
  • Mobilization of Pb from bone occurs during pregnancy and lactation which can increase fetal exposure, and after menopause with onset of osteoporosis which can increase exposure to soft tissues
• Acute Lead Exposure


  • Gastrointestinal Distress
  • Destruction of Red Blood Cells
  • Serious Brain Swelling
  • Vomiting
  • Irritability and Restlessness
  • Progressive Drowsiness
  • Tremors and Seizures
  • Coma
  • Muscle pain
  • Death
• Chronic Lead Exposure


  • Impaired hemoglobin synthesis
  • Hypertension
  • Alteration in the central and peripheral nervous systems
  • Damage to the male and female reproductive systems
  • Damage to developing fetus (lead freely crosses the placenta)
• Sensitivity of Children to Lead

  • Even though blood Pb levels are decreasing in the general population, still 35% of inner city children have blood Pb concentrations above 10 µg/dl
  • Higher exposure from Pb-based paint in homes and urban dust due to childhood behaviors
  • Higher rate of intestinal absorption in children and nutritional deficiencies in iron and calcium which enhance Pb absorption
• Toxic Effects of Lead in Children

  • Lead encephalopathy occurs at 80 µg/dl
  • Symptoms: Begin with lethargy, vomiting, irritability, loss of appetite and dizziness
  • Progress to ataxia, reduced level ofconsciousness, coma and death
  • Pathology involves edema of brain due to extravasation of fluid from capillaries, loss of neuronal cells and increase in glial cells
  • Recovery is accompanied by epilepsy, mental retardation, optic neuropathy and blindness
• Stems


  Damage to developing fetus (lead freely crosses the placenta)
• Sensitivity of Children to Pb

  • Even though blood Pb levels are decreasing in the general population, still 35% of inner city children have blood Pb concentrations above 10 µg/dl (recommended by CDC to prevent impairment of cognitive and behavioral development)
• Higher exposure from Pb-based paint in homes and urban dust due to childhood behaviors
• Higher rate of intestinal absorption in children and nutritional deficiencies in iron and calcium which enhance Pb absorption
• Lead encephalopathy


  Occurs at 80 µg/dl
• Pathology involves edema of brain due to extravasation of fluid from capillaries, loss of neuronal cells and increase in glial cells
• Recovery is accompanied by epilepsy, mental retardation, optic neuropathy and blindness
• Peripheral neuropathy


  Classic manifestation of Pb toxicity at blood Pb levels above 40 µg/dl
• "Footdrop" or "wristdrop " due to segmental demyelination and axonal degeneration with Schwann cell degeneration
• Sensory nerves are less sensitive than motor nerves
• CNS effects (changes in mood and affect) occur at higher blood levels than in children
• Anemia


  Occurs from shortened lifespan of red blood cells
• Inhibition of pyrimidine -5-nucleosidase leads to nucleotide accumulation which affects membrane stability of red blood cells
• Impairment of heme synthesis limits recovery of red blood cell populations