HEAVY METAL POISONING HEAVY ■ ■ ■ ■ ■ METALS Specific gravity at least 5 times that of water Most common: Pb, Hg, As, Cd Heavy metals of use – Trace elements – Zn, Cu, Cr, Mn, Fe Entry into body – inhalation, ingestion, skin , IV Compete and displace essential minerals – Zn, Cu, Mg, Ca ■ SYMPTOMS: Depend on nature and quantity ■ NVD, stomach pain, headache, sweating, metallic taste ■ Impairment of cognitive, motor, language skills ■ DIAGNOSIS: ■ Difficult without suspicion as symptoms vague. ■ Blood and urine tests. ■ Hair and tissue analysis ■ X rays of specific regions ARSENIC ■ ■ ■ ■ ■ ■ ■ Most common heavy metal poisoning and is second to lead with respect to chronic poisoning It is a transition metal or metalloid belonging to nitrogen family- hence it forms compounds with metals as well as covalent bonding with wit C, H, O Form : Metalloid form – 0 OS / arsenite - +3/ arsenate - +5 Pure arsenic – Black metallic sheen – not poisonous in healthy people Toxicity : ARSINE >>>>> Inorganic trivalent > Organic trivalent > inorganic pentavalent > organic pentavalent > arsenic Toxicity : Physical state (gas, solution., powder) / particle size / rate of absorption and elimination ARSENICALS ARE NOT CUMULATIVE – toxicity parallels excretion ARSENIC SOURCES ■ Natural / Industrial / Intentional administration NATURAL: ■ sea water: 0.006 – 0.03 ppm th ■ 20 most common element in earths crust ■ Geothermal areas – as high as 20ppm ■ Years of pesticide spraying – several hundred ppm ■ Average daily intake – 0.5 – 1 mg from food and water ■ Highest in fish and crustaceans –Increased excretion after sea food meal ■ Normal body – 20 mg INDUSTRIAL: ■ Metal industry, fertilizer and pesticide spraying ■ Useful as wood preservatives, pesticides, herbicides, fungicides, dyes, printing,, wall paper and war gases. ■ Very much used in electronic industry ■ Staffordshire beer syndrome – glucose used – H SO from ores 2 4 with arsenic ENVIRONMENTAL ■ sulfide complexes – realgar As S , orpiment As S , iron pyrites 2 2 2 3 FeAsS ■ contaminant of lot of metal ores ■ when heated white powder of arsenic trioxide called arsenic ■ arsenic epidemic in Bangladesh INTENTIONAL ADMINISTRATION ■ ■ ■ ■ ■ Hippocrates – orpiment and realgar as escharotics and for ulcer treatment Paracelsus – various compounds extensively All substances are poisonous, there is none which is not. The right dose differentiates a poison from a remedy. Used by women to highlight their complexion – capillary flush – milk and roses complexion Arsenic compounds used for TB, rheumatoid arthritis, diabetes, skin disorders, neuralgia and haematological disorders MISUSES: ■ ■ Best poison of the middle ages Napoleon Bonaparte- either poisoned or wall paper with compounds paris green or scheels green – moulds action – trimethyl arsine Compounds of Arsenic ■ ■ ■ ■ ■ ■ Sankhya or somalkar – AsO, As2O3 – Fowlers solution Cu arsenite (scheeles green), Cu acetoarsenite (paris green) – (Hirwa) coloring agent for toys, wall paper As sulfides – depilatories As compounds of Pb, Na, K – weedicides, insecticide, fungicide Organic arsenicals – trypnosomiasis, amoebiasis Arsine gas - industry Mechanism of Action All compounds are not poisonous Increased permeability of small blood vessels, inflammation of intestinal mucosa- hmrgic GE- fluid loss Tissue toxicity ■ ■ ■ ■ ■ Toxicity of As due to inhibition of sulfhydril containing enzymes by As +3 – enzymes deactivated – reactivated by addition of monothiols (glutathione) –proof of sulfhydril group Pyruvate oxidase – complexes with 2 sulfhydril groups forming a ring 2,3 dimercaptopropanolol – BAL Uncoupling of oxidative phosphorylation Arsine gas – hemotoxic – RBS hemolysis CLINICAL MANIFESTATONS ACUTE POISONING: ■ Usually within 30 minutes of exposure ■ Metallic taste with garlicky odour with dry mouth and dysphagia ■ Severe nausea and vomiting with abdominal colic, profuse diarrhea with rice water stools ■ ENDOTHELIAL CELL TOXICITY ■ Capillary damage -vasodilatation -transudation - SHOCK ■ Hypovolemia – cyanosis, hypoxic encephalopathy and seizures, ATN and death ■ After GI phase – MODS ■ If death not by shock the delayed due to hepatic/ renal failure ■ Cardiac – myopathy, SEH, ECG – prolonged QT interval and STT changes – torsades de pointes CHRONIC POISONING ■ ■ ■ ■ ■ ■ ■ Accidental/ homicidal/ occupational Min 2 – 8 weeks GIT : NVD, colic, furry coated tongue, periorbital edema of lower lids, cirrhosis SKIN: faded measles rash/ raindrop pigmentation/ hyperkeratosis of palms and soles/ striate leuconychia – Mee’s lines HAEM: BM supression, Decreased cells, Leukemia PNS: distil symmetrical sensory and motor polyneuropathy – stocking glove pattern NEOPLASTIC: cancers of lung, skin, liver, bone marrow DIAGNOSIS: ■ ■ ■ ■ ■ Acute poisoning – X ray abdomen Serum As - >7ug% Measurement of urinary As levels - + in few hrs to weeks post injestion Detection in skin, hair and nails Highest concentration in liver, also seen in muscles, bones. MANAGEMENT: ■ ■ Supportive and chelation therapy Supportive therapy: ■ ■ ■ ■ ■ ■ ■ Emesis induction Stomach wash Freshly prepared hydrated Fe2O3 ACTIVATED CHARCOAL Cathartics/ demelcunts to lessen irritation Intravenous fluids Exchange transfusion/ hemodialysis CHELATION THERAPY ■ ■ ■ ■ Dimercaprol 3-5 mg/kg every 4 hrs till urinary As excretion is below 50 micrograms in 24 hrs Na EDTA/ Penicillamine are also useful DMSA – succimer – more effective in reducing As content of tissues and not cause increased accumilation of As in brain POST MORTEM APPEARANCE ■ ■ ■ ■ ■ ■ ■ ■ Non specific Erosions, ulcerations of GI tract Longer duration of rigor mortis Dehydrated shrunken body Keratotic features and hyper pigmentation and rash Red velvety stomach Petechial haemorrhages on heart, lungs and other organs seen Fatty degeneration of liver, spleen and kidneys. LAB DETECTION: ■ Marsh Test: ■ ■ ■ ■ Reinsch’s test: ■ ■ ■ ■ Formation of AsH3 – burns with greenish blue flame with garlicky odour – stain on cooling Stain soluble in hypochlorite but not in ammonium sulphide Very very sensitive Material boiled with HCL Cu strip introduce will have steel grey coating Strip heated – white octahedral crystals of As2O3 MEDICOLEGAL IMPORTANCE Trait Arsenic poisoning Cholera Throat pain Before vomiting After vomiting Purging After vomiting Before vomiting Stools Rice watery and bloody Present Rice watery Conjunctiva Inflamed Not inflamed Other skin features Present Absent Urine and feces examination As present Vibrio present Tenesmus and irritation Absent Keratosis on hands Keratosis on soles MERCURY (quick silver) MERCURY POISONING ■ ■ Only metal liquid at room temperature 3 forms ■ ■ ■ ■ ■ Metallic form – non poisonous as not absorbed Active form ■ ■ ■ Metallic Mercurous Mercuric Mercuric – soluble; dangerous Mercurous – insoulble; less toxic Bioaccumilative poison Mechanism of action: ■ Inhibits sulfhydril groups containing enzymes ■ Pyruvate dehydrogenase Compounds of Mercury: ■ Mercuric chloride – corrosive sublimate; MC source ■ Mercuric sulphide – cinnabar; red crystalline powder ■ Organic mercurials: Insecticides/ rodenticides/ fungicides Methyl mercury – minamata disease Dimethyl mercury – MOST LETHAL Ethyl mercury – thimerosal Sulfocyanide of mercury – Pharoah’s serpent PHARMACOKINETICS ■ ■ ■ ■ ■ ■ ■ Soluble in gastric juice – absorption + for HgCl Vapours rapidly absorbed through RS – symptoms++ Precipitation in liver, spleen, kidney and bones Inhalation – max deposition in brain Organic compounds – placenta – fetal abnormalities Normal daily in take – 5 to 20 µg Excreted in bile, urine and feces ACUTE POISONING ■ ■ Ingested/ inhaled Metal fume fever (Vapours) cough/ dyspnoea/ fever with rigors metallic taste/ blurring of vision (II CN) ■ Ingestion: metallic taste/ burning sensation in GIT corrossion of mucus membranes Vomitus – mucus, altered blood and shreds of gastric mucosa Diorrhoea – tenesmus, necrosed colonic mucosa DIAGNOSIS ■ History ■ Mercury levels ■ ■ Blood (<=3.6 ; >20 µg/dL) Urine ( <= 15 ; >60 µg/L) POST MORTEM FEATURES ■ External: corrosion ■ Internal: ■ ■ ■ MM – necrotic and corroded GIT – ulcerations; necrosis / caecum and LI max Kidney – ATN/ Liver – fatty degneration MANAGEMENT CLEARING GIT: ■ Emesis ■ Stomach wash : ■ ■ Egg white (Hg albuminate/ activated charcoal) 250 mL of 5% Na formaldehyde sulphoxylate – converts into harmless insoluble mercurous compounds- Lavage CLEARING ABSORBED POISON: ■ Chelating agents – dimercaprol/ penicillamine/ EDTA ■ Peritoneal/ Haemo dialysis Chronic Mercury poisoning (hydrargyrism) Occupational exposure ■ Traditional medicinal preparations ■ Dermatological ointments ■ ■ ■ ■ Increased salivation/ metallic taste/ painful inflamed gums Blue line on gums (not Burtonian line) Mercuria lentis: ■ ■ ■ early symptom of chronic poisoning discoloration of ant. Capsule of lens Neurological toxicity: ■ ■ HgNO3 – hat making industry – Danbury – Connecticut – USA Danbury tremor: ■ ■ ■ ■ Earliest manifestation of neurological toxicity Coarse/ intentional/ hands, arms, tongue and last legs Hatters shakes Concussio mercurialis: ■ ■ No activity possible Stammering speech/ unable to do daily activities ■ Mercurial erethism: ■ ■ ■ ■ mirror manufacturing industry personality changes memory loss/ timidity/ depression/ delusions& hallucinations, (MAD HATTER) Acrodynia: ■ ■ ■ ■ ■ ■ Pink disease Generalized pinkish body rash fever, irritability, photophobia increased sweating, desquamation of hands and feet, epilation, hyperkeratosis Hypersensitivity to mercurous chloride Common in children TREATMENT ■ environmental and occupational change ■ chelation therapy MEDICOLEGAL IMPORTANCE ■ mostly accidental or occupational poisoning ■ accidental in children – pharaohs serpent – sulfocyaninde of mercury ■ Amalgam in gold extraction – environmental poison ■ Dental amalgam LEAD LEAD ■ ■ ■ Metallic lead not poisonous until and unless some mucosal erosions in gut Salts of lead are poisonous if ingested, inhaled, infused. Types of compounds and their uses: Lead acetate (sugar of lead) Lead carbonate (white lead) Astringent and LA Paints Lead tetroxide (red lead) Lead sulphide (surma) Lead oleate Tetraethyl lead Sindoor Eye liner Abortifacient, plaster Anti knock in petrol METABOLISM ■ ■ ■ ■ ■ ■ ■ ■ Absorbed through ingestion/ inhalation Tetraethyl lead – some absorption through skin Absorbed into plasma and distributed to tissues 95 – 99% of lead sequestered into RBC – whole blood Largest portion of absorbed lead into bones >90% of total body lead burden T1/2: blood – 25 days/ soft tissues – 40 / bone - >25 yrs Excreted mainly in urine and feces Present in nails, skin, saliva, hair, breast milk etc MECHANISM OF TOXICITY ■ ■ ■ ■ ■ Inhibits sulfhydril group containing enzymes Lead affinity to cell membranes and mitochondria Enzymes necessary for heme synthesis – microcytic or normocytic hypochromic anaemia δ aminolevulinic acid to porphobilinogen – ALA dehydrase – blocked by Pb- increased δALA in blood and urine Protoporphyrin IX to heme – ferrochelatase – inhibited by Pb - increased FEP levels (free erythrocyte protoporphyrin) ACUTE POISONING ■ Symptoms similar to As poisoning ■ Not diarrhoea but CONSTIPATION – black and offensive stools - PbS ■ Metallic taste in mouth, N&V, abdo. colic ■ painful cramps in legs and arthralgia in protracted cases ■ Peripheral circulatory collapse MANAGEMENT ■ Emesis and lavage with Na SO – PbSO - insoluble 2 4 4 ■ Ca gluconate – relieves abdo. Colic and bone deposition ■ Ca EDTA – slow infusion – chelates Pb ■ Penicillamine is an alternative CHRONIC POISONING (plumbism or saturnism) ■ ■ ■ ■ ■ Industrial environment – paints, batteries, glass manufacture, dyes, cosmetics Drinking water in lead pipes or stored in lead containing vessels Either over long duration exposure or release of stored lead in bones – Acute on chronic Petrol fumes inhalation – traffic constables etc Acidosis dangerous than alkalosis as causes Pb release from bones CLINICAL FEATURES 1 Facial pallor 2 Anaemia Earliest and most common Capillary vasospasm (circum oral) Initial polycythemia later anaemia Enzyme inhibition – polychromasia, reticulocytosis, aniso and poikilocytes Basophilic stippling – Fe containing RNA near mitochondria – pyrimidine nucleotidase inhibition Increased porphyrins in urine 3 4 5 Lead line Burtonian line Sub epithelial deposition of PbS Lead colic/ seen in >85 % of patients constipation colic on intestines, ureters, uterus, blood vessels Spasmodic intermittent and relieved by pressure Lead palsy <10% of cases and adults >children peripheral demyelination with atrophy muscles prone to fatigue – wrist extensors (wrist drop), ankle extensors (ankle drop) Recovery slow 6 Encephalopathy 7 Others more in children and TEL inactivation of MAO by Pb interacting with SH groups personality changes, mental dullness, convulsions, coma and death chronic arteriosclerotic nephritis menstrual irregularities and sterility alopecia Mnemonic for lead poisoning ■ ■ ■ ■ ■ ■ ■ ■ ■ Anaemia/ arthralgia/ abortion/ atrophy of II CN Basophilic stippling/ Burtonian line on gums Colic/ constipation/ coproporphyrin in urine Drop (wrist, foot) Emaciation/ encephalopathy Fouls smell/ failure of kidneys/ Fanconis syndrome Gonadal dysfunction High BP/ headache/ hyperesthesia impotence./ insomnia/ irritability DIAGNOSIS ■ ■ ■ History, clinical features etc Blood level – normal : 0 – 50 µg/dl Chelation therapy ■ ■ ■ ■ in children if > 55 µg/dl adults > 80 µg/dl without symptoms Adults > 60 µg/dl with symptoms Coproporphyrin in urine ■ Normal <150 µg/L ■ ALA in urine : > 5mg indicate poisoning X ray – increased density in bone and at metaphysis in children Management ■ Medicolegal importance ■ ■ Thank you
