Trace Metals

Question 1

Mercury - source, forms, kinetics, toxicity effects, investigations, treatment

Answer 1

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

Question 2

Arsenic - source, toxic form, toxicity effects, investigations, treatment

Answer 2

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

Question 3

Lead - sources, kinetics, toxicity effects, investigations, treatment

Answer 3

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

Question 4

Cadmium - sources, kinetics, toxicity, investigations, treatment

Answer 4

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)

Question 5

Essential elements - function, deficiency, toxicity

Answer 5

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