Trace Metals Flashcards
Mercury - source, forms, kinetics, toxicity effects, investigations, treatment
Sources:
- jewellers, dye, disinfectant
- dental amalgam
- predatory fish
Forms: organic, inorganic and elemental
Kinetics:
- organic Hg well absorbed in the gut and REDISTRIBUTED TO BRAIN (3-6x levels of blood)
Toxicity:
- organic>inorganic>elemental
- 175 nmol/L as action limit
Organic – CNS and LIVER
- concentric constriction of bilateral visual fields, blurred vision, paresthesia of extremities and mouth, ataxia, deafness etc
Inorganic – KIDNEY ONLY
- may develop renal failure due to toxic effect on renal tubular cells (especially PCT) –> membranous GN and nephrotic syndrome
- chronic = acrodynia
Elemental – CNS and KIDNEY
- cough, chills, SOB, fever
- chronic = erethism
Investigations:
- BLOOD levels (organic Hg)
- urine levels (inorganic Hg)
- urine protein (effects of inorganic Hg)
- hair levels (organic Hg - not widely used) – ONLY METAL THAT CAN BE ANALYSED USING HAIR! (not reflecting body load for other metals)
Treatment:
- inorganic and elemental – BAL
- organic – NOT BAL! (may redistribute chelated metal to sensitive tissues and worsen symptoms); use DMSA chelation
Arsenic - source, toxic form, toxicity effects, investigations, treatment
Sources
- insecticide
- seafood (rich source of organic As - non-toxic)
Toxic inorganic form
- trivalent As (III) binds to sulphydryl groups on critical enzymes –> deplete lipoate and inhibit TCA and gluconeogenesis ==> PERIPHERAL NEUROPATHY, INTRAVASCULAR HAEMOLYSIS and AKI
- pentavalent As (V) replace phosphate ester bond in ATP –> unstable “ATP” rapidly hydrolysed –> deplete ATP stores ==> FATIGUE, LOW CO
==> INHIBIT CELLULAR RESPIRATION and UNCOUPLE OXIDATIVE PHOSPORYLATION = cellular energy depletion
Investigations
- AVOID SEAFOOD FOR 5 DAYS to prevent contamination by organic As
- URINE levels
- blood for acute poisoning (short t1/2 of 1-2 hrs)
Treatment
- chelation by DMSA, BAL, Penicillamine
Lead - sources, kinetics, toxicity effects, investigations, treatment
Sources
- non occupational: lead water pipes, glazed jugs, lead crystal bottles or glasses, newsprint, lead paint, varnish, polishes, cable chewing
- industrial exposure: car/ship wrecking, construction, paint manufacturing, metal smelter
Kinetics: bone t1/2 = 30 yrs (95% of body Pb)
Toxicity
- organic Pb: euphoria, hallucination
- inorganic Pb:
- -> chemically similar to Ca –> interfere with Ca dependent pathways e.g. increased vascular smooth muscle contraction (increased activity of Na-Ca pump) ==> HYPERTENSION, GASTRIC COLIC
- -> haematological effects: REDUCED RBC LIFESPAN AND DECREASED Hb SYNTHESIS
- inhibition of pyrimidine-5’-nucleotidase and inhibition on Na-K ATPase –> decrease energy use and membrane stability of RBC; decreased removal of RNA (BASOPHILIC STIPPLING)
- interfere with enzymes in Hb synthesis pathway (Ala dehydratase, ferrochelatase) –> HcMc anaemia
==> acute: decreased hearing, Fanconi’s syndrome
==> chronic: Mees’ line, segmental demyelination, anaemia, decrease cognitive development
Investigations
- toxicity related to blood levels
- WHOLE BLOOD Pb (95% RBC bound)
- Urine Pb
- activity of Ala DH – most sensitive (but too sensitive in workers)
- EDTA mobilisation test (test chelatable body store, not for >40!)
Treatment
- limit further exposure (protective gear, improve working environment)
- chelation for symptomatic adults with Pb >70
- -> DMSA (succimer), EDTA, pencillamine, BAL
Cadmium - sources, kinetics, toxicity, investigations, treatment
Sources
- diet: shellfish, pork
- smoking
- industrial exposure
Kinetics: 90% RBC bound; excrete then reabsorb and go to kidneys
Toxicity
- acute: pneumonitis
- chronic: ITAI-ITAI disease (osteomalacia, bone pain, pathological fracture), irreversible renal tubule damage when >200 mcg/g
Investigations
- WHOLE BLOOD AND URINE
- reflects burden in chronic exposure (>10 = renal damage, presence of proteins; acute exposure may be >50 but not a/w renal damage)
Treatment
- avoid exposure
- CHELATION CONTRAINDICATED (released Cd exacerbates renal damage)
Essential elements - function, deficiency, toxicity
Iron
- haem
- HcMc anaemia
- corrosive to GI tract
Iodine
- thyroid hormone
- goitre, cretinism
Copper
- many enzymes; increase in acute phase reaction, ceruloplasmin bound
- impaired immunity, hair, nail growth
- Wilson disease
Chromium
- enhance insulin action (CrIII); CrV is allergen
- rare deficiency
- artificial joints, dermatitis
Selenium
- component of glutathione peroxidase; RBC glutathione peroxidase as tissue marker
- keshan syndrome (cardiomyopathy)
- dermatitis, conjunctivitis
Zinc
- component of many enzymes; decrease with fasting and acute phase reaction, albumin bound
- growth retardation, acrodermatitis enteropathica
- pneumonitis, sideroblastic anaemia
