DiversityDiversity ofof TraceTrace ElementsElements andand ToxicToxic MetalMetal IonsIons inin EnvironmentalEnvironmental HealthHealth andand HumanHuman DiseasesDiseases JosJoséé A.A. CentenoCenteno U.S. ARMED FORCES INSTITUTE OF PATHOLOGY Washington, DC Email: [email protected] OutlineOutline •• IntroductionIntroduction toto TraceTrace Elements,Elements, MetalsMetals andand MetalloidsMetalloids •• TraceTrace ElementsElements andand KnownKnown Biological/ToxicologicalBiological/Toxicological ReactionsReactions •• EnvironmentalEnvironmental HealthHealth andand DiseasesDiseases •• ConcludingConcluding RemarksRemarks Suggested Reading: Essentials of Medical Geology (Selinus et al. 2005). Chapters on Nutrition (Gerald T. Combs), Biology of Trace Elements (Ulf Lindh)). Natural Non- deposits industrial Drinking water Food Industrial Agriculture Mining/smelting Coal burning Micro-electronics Science, Vol 300, May 2003 From Harold H. Sandstead, MD collection University of Texas From Harold H. Sandstead, MD collection University of Texas GeochemistryGeochemistry ofof SomeSome EssentialEssential ElementsElements AffectsAffects HumanHuman HealthHealth •• SomeSome essentialessential elementselements whosewhose geographygeography is,is, oror isis presumed,presumed, directlydirectly relatedrelated toto humanhuman health:health: •• I,I, Se,Se, F,F, Cr,Cr, Mo,Mo, BB •• SomeSome essentialessential elementselements whosewhose geographygeography isis apparentlyapparently notnot directlydirectly relatedrelated toto humanhuman health:health: •• Fe,Fe, Zn,Zn, Cu,Cu, Ca,Ca, MgMg CriteriaCriteria forfor EssentialityEssentiality •• WithdrawalWithdrawal oror absenceabsence ofof thethe metalmetal fromfrom thethe dietdiet producesproduces eithereither functionalfunctional oror structuralstructural abnormalities,abnormalities, andand thatthat thethe abnormalitiesabnormalities areare relatedrelated toto oror areare aa consequenceconsequence ofof specificspecific biochemicalbiochemical changeschanges thatthat cancan bebe reversedreversed byby thethe presencepresence ofof thethe essentialessential metal.metal. •• RoleRole:: AsAs catalystcatalyst inin cellularcellular functions.functions. •• Sources:Sources: MustMust bebe obtainedobtained fromfrom air(oxygen),air(oxygen), waterwater anan dietdiet •• Concentration:Concentration: neededneeded onon mcgmcg toto mgmg Sixteen trace elements are established as being essential for good health. These, collectively, have five general physiological roles: •• bonebone andand membranemembrane structurestructure •• waterwater andand electrolyteelectrolyte balancebalance •• metabolicmetabolic catalysiscatalysis •• oxygenoxygen bindingbinding andand transporttransport •• hormonehormone effectseffects •• bonebone andand membranemembrane structurestructure •• waterwater andand electrolyteelectrolyte balancebalance •• metabolicmetabolic catalysiscatalysis •• oxygenoxygen bindingbinding andand transporttransport •• hormonehormone effects effects •• bonebone andand membranemembrane structurestructure •• waterwater andand electrolyteelectrolyte balancebalance •• metabolicmetabolic catalysiscatalysis •• oxygenoxygen bindingbinding andand transporttransport •• hormonehormone effects effects •• bonebone andand membranemembrane structurestructure •• waterwater andand electrolyteelectrolyte balancebalance •• metabolicmetabolic catalysiscatalysis •• oxygenoxygen bindingbinding andand transporttransport •• hormonehormone effects effects •• bonebone andand membranemembrane structurestructure •• waterwater andand electrolyteelectrolyte balancebalance •• metabolicmetabolic catalysiscatalysis •• oxygenoxygen bindingbinding andand transporttransport •• hormonehormone effects effects •• bonebone andand membranemembrane structurestructure •• waterwater andand electrolyteelectrolyte balancebalance •• metabolicmetabolic catalysiscatalysis •• oxygenoxygen bindingbinding andand transporttransport •• hormonehormone effects effects OutlineOutline •• IntroductionIntroduction toto TraceTrace Elements,Elements, MetalsMetals andand MetalloidsMetalloids •• TraceTrace ElementsElements andand KnownKnown Biological/ToxicologicalBiological/Toxicological ReactionsReactions •• EnvironmentalEnvironmental HealthHealth andand DiseasesDiseases •• ConcludingConcluding RemarksRemarks ACTIONACTION OFOF MACRONUTRIENTSMACRONUTRIENTS Ca Strengthening of bones and teeth; muscular activity; blood coagulation; cellular permeability. Excess may originate liver and bladder stones and renal insufficiency. Cl Maintenance of blood pressure; vital as acid constituent during digestion. K Maintenance of corporeal fluids; muscular contractions and nervous impulses. Mg In bones, together with Ca; activation of muscular contractions; body temperature control; component of several enzymes. Na Active in hydrosaline equilibrium; transmission of nervous impulses and transport of metabolites. P Bone constituent as apatite; participates in most body chemical reactions. Excess turns hair and bones brittle. Scarpeli, William (personal communication) ACTIONACTION OFOF MICRONUTRIENTSMICRONUTRIENTS Co Active in vitamin B12 and in chemical reactions. Deficiency causes anemia. Excess causes hearth failures. Cr Needed for metabolism of sugar. Deficiency may cause diabetes, intolerance to glucose etc. Excess may result in renal failures. Excess of Cr+6 is carcinogenic. Cu Component of oxidizing enzymes during metabolism of energy sources; active in the synthesis of hemoglobin, in keratization and in skin and hair pigments. Deficiency leads to osteoporosis and low number of white blood cells. F Give strength to teeth and bones, avoiding dental caries and osteoporosis. Excess causes fluorosis of teeth and bones. I Required by thyroidal hormones, temperature control, body growth, reproduction etc. Deficiency causes abnormal growth of the thyroid. Scarpeli, William (personal communication) elementselements relatedrelated toto cardiaccardiac healthhealth antioxidant protection antioxidant protection; insulin potentiation regulation of thymulin and IL-2 antioxidant protection antioxidant protection, regulation of PG metabolism TraceTrace ElementsElements inin EnvironmentalEnvironmental HealthHealth •• ExposureExposure Routes:Routes: Inhalation Ingestion – Direct Absorption – Air (inhaling) – Drinking water – Diet (food chain) •• MetalMetal--InducedInduced Disease:Disease: – Carcinogenic Dermal contact – Teratogenic – Mutagenic CancerCancer andand SiteSite SpecificSpecific EffectsEffects AssociatedAssociated withwith ExposureExposure toto ToxicToxic TraceTrace MetalsMetals Examples:Examples: Element Target Organ and/or Sites → Cr Lung, Liver, Kidney → As Bladder, Liver, Lung, Skin, Vascular, Neurological changes → Cd Lung, Kidney, Bladder, Vascular, Hypertension, Neurological changes → Hg Neurological, lung, kidney, Brain → Pb Neurological, IQ(children), Anemia OutlineOutline •• IntroductionIntroduction toto TraceTrace Elements,Elements, MetalsMetals andand MetalloidsMetalloids •• TraceTrace ElementsElements andand KnownKnown Biological/ToxicologicalBiological/Toxicological ReactionsReactions •• EnvironmentalEnvironmental HealthHealth andand DiseasesDiseases •• ConcludingConcluding RemarksRemarks Trace Element Malnutrition in Developing Countries 600 500 400 anemia, women goiter, all ages 300 Zn deficient 200 Se deficient millions of people 100 0 Courtesy from Dr. Gerald T. Combs TRACETRACE ELEMENTSELEMENTS ANDAND TOXICTOXIC METALMETAL IONSIONS HEALTHHEALTH EFFECTSEFFECTS DeficienciesDeficiencies IronIron (Fe):(Fe): TheThe mostmost widelywidely abundantabundant micronutrientmicronutrient • Essential constituent of: Hemoglobin, myoglobin, e-transport enzymes, oxidases; • Human Body: 2-6 g or iron ; metabolic function is to transport oxygen and electrons (redox agent); • Iron Deficiency (ID): Anemia, fatigue, susceptibility to infection and impairment of cognitive development, increased risk of Pb poisoning; • Pregnancy: increases the risk of premature delivery, low birth weight and infant and maternal mortality • Iron Toxicity: Liver and increase risk of coronary heart diseases (adults), Iron-overload (children) • Clinical Signs (Fe > 10-fold excess): cirrhosis, diabetes, heart failure, arthritis, and sexual dysfunction. GlobalGlobal PrevalencePrevalence ofof AnemiaAnemia • >2.1 B affected – 43% of women, 34% of men in 70 developing countries 60 • multiple causes: 50 – malaria, intestinal parasites % – deficiencies of Fe, vit A, folate, vit B12 40 • reduced work capacity 30 • 20% of maternal deaths 20 – hemorrhage, heart failure 10 • 1/3 of child deaths 0 • impaired cognitive learning Afr LAm Asia NAm Courtesy from Dr. Gerald T. Combs ZnZn DeficiencyDeficiency (ZD)(ZD) GlobalGlobal PrevalencePrevalence • Similar to ID; likely widespread, but not well documented. • Infants, children, pregnant and premenopausal women, and elderly at higher risk. • impairs immunity, vit A utilization • Some clinical effects of ZD: – Abortion – Growth stunting (children) – Development delay – Decrease immunity – Dermatitis – Decrease neuropsychological functions – Behavior problems – Dementia SomeSome causescauses ofof zinczinc deficiencydeficiency PrimaryPrimary SecondarySecondary –– PoorPoor foodfood choiceschoices -- BloodBlood lossloss –– ReducedReduced bioavailabilitybioavailability -- GIGI diseasesdiseases –– GeophagiaGeophagia MalabsorptionMalabsorption InflammationInflammation -- LiverLiver diseasesdiseases -- RenalRenal losseslosses TRACETRACE ELEMENTSELEMENTS ANDAND SELECTEDSELECTED ENDEMICENDEMIC DISEASESDISEASES