ARSENIC AND LEAD POISONING

ARSENIC AND LEAD POISONING IN CLINICAL TOXICOLOGY

1. CLINICAL TOXICOLOGY PREPARED BY, NIBY, IV-PHARM-D ARSENIC AND LEAD POISONING

2. ARSENIC POISONING

3. arsenic: Arsenic is thought to occur through out the universe. It is the twentieth most common element in the earth’s crust, having a concentration of 1.8 ppm. Arsenic is today the commonest source of acute heavy metal poisoning , and is second only to lead in the incidence of chronic toxicity. It exists in compounds that may be organic or inorganic. Elemental arsenic is the least toxic.

4. Physical appearance: Arsenic is a metalloid i.e. it is an element which resembles a metal in some respects, and is by itself not very toxic. Arsenic is a silver-grey or tin white, shiny, brittle, crystalline, and metallic looking element. It is rarely found in its isolated, elemental form. More commonly it is present in mineral species in alloys or as an oxide or other compound form.

5. Inorganic and organic arsenicals CHEMICAL NAME USES 1 ELEMENTAL ARSENIC In alloys 2 ARSINE Lead plating,soldering,galvanising , and in electronic components 3 TRIMETHYL ARSINE Present in sewage 4 ARSENIC TRIOXIDE Manufacture of glass ,insecticide, rodenticide,previously used in medicine for fever(Flower’s solution) 5 ARSENIC TRICHLORIDE Pottery 6 SODIUM ARSENITE Wood preservative,insecticide , veterinary use 7 ARSENIC PENTOXIDE Manufacture of coloured glass,insecticide ,wood preservative 8 LEAD ARSENATE Insecticide 9 SULPHIDES OF ARSENIC Depilatory 10 COPPER ARSENATE Colouring agent for toys, wallpaper,etc . 11 ORGANIC ARSENICALS( carbarsone,tryparasamide,glycobiarsol ) Previously used in therapeutics

6. USUAL FATAL DOSE: 200-300 mg for arsenic trioxide. In general,the pentavalent form of arsenic (arsenate) is less toxic than the trivalent form( arsenite ) because it is less water soluble. The most toxic form is arsine gas(25-30 ppm can be lethal in 30 minutes)

7. Toxicokinetics and mode of action: Arsenic is absorbed through all portals of entry including oral, inhalational, and cutaneous routes. After absorption it is redistributed to the liver , lungs, intestinal wall, spleen, where it binds to the sulfhydryl groups of tissue proteins. Arsenic replaces phosphorus in the bone where it may remain for years. It gets deposited also in hair. While arsenic does not crosses the blood brain barrier easily, it crosses the placenta readily and can give rise to intrauterine death of the feotus . In less severe intoxications it can cause respiratory distress of the newborn due to pulmonary haemorrhage and hyaline membrane formation.

8. Clinical features: SYSTEM ACUTE CHRONIC DERMAL Hair loss,transverse bands of opacity in nails. melanosis ( neck,yelids,nipples ) bowen’s disease,facial oedema,hyperkeratosis,hyperpigmentation,skin cancer. OCULAR Conjunctivitis, lacrimation Dimness of vision GI Abdominal pain, metallic taste, dysphagia , vomiting, bloody or rice-water diarrhoea . Garlicky odour in breath Anorexia, nausea, vomiting, diarrhoea,weight loss AIRWAYS Irritation of upper airways Perforation of nasal septum, chronic laryngitis, bronchitis LIVER Fatty degeneration Hepatomegaly , jaundice, cirrhosis KIDNEY Oliguria , uraemia Nephritic changes NEUROLOGICAL Hyperpyrexia, convulsions,coma Encephalopathy, polyneuritiss , tremor, ataxia, limb tenderness, difficulty in walking CARDIAC Tachycardia, hypotension, cardiac arrhythmias. Hypotensin , myocarditis

9. Diagnosis: Urine level: if the 24 hr excretion of arsenic exceeds 100mcg, it is indicative of toxicity. Blood level: less reliable than urine level because of short half life of arsenic in blood.A level of arsenic less than 7mcg/100ml-normal range. Hair level: possibility of scalp hair being contaminated with arsenic from the environment. Radiography: arsenic is radio- opaque,abdominal x-ray reveals its presence in GIT in acute poisoning. Additional investigation: Monitor CBC, serum electrolytes, urinalysis, liver and renal functional tests. Obtain ECG- Cardiac monitoring. Chest radiography with severe poisoning or pulmonary effects.

10. Treatment: Supportive measures: gastric lavage , intravenous fluids, cardiac monitoring, etc. 2. Chelation therapy: This can be done with – BAL(British Anti Lewesite or dimercaprol )- 3to5mg/kg IM every 4 hrs until the urinary excretion dips below 50mcg/24hrs . Usual duration of therapy is 7to10 days. Penicillamine – can be given orally at a dose of 100mg/kg/day, 6 th hourly for 5 days. DMSA( Dimercapto succinic acid), or DMPS( Dimercapto propane sulfonic acid).- superior to BAL and penicillamine .

11. Principles of chelation : Begin chelation therapy in symptomatic patients. The urine arsenic level which should prompt chelation in an asymptomatic patient has been recommended as 200mcg/ litre . Repeat courses of chelation therapy should be prescribed in severe poisonings until the 24-hr urine arsenic level falls below 50 mcg/ litre . Chelation therapy is not very effective for chronic poisoning and is totally ineffective in arsine poisoning. The later should be treated with emphasis on respiratory stabilisation and haemodialysis . 3. Haemodialysis or exchange transfusion.

12. LEAD POISONING

13. LEAD: Lead is the commonest metal involved in chronic poisoning. It was one of the first metals known to man and has been widely used during the last two thousand years of domestic, industrial, and therapeutic purposes. Lead is abundant in soil, being distributed throughout the earth’s crust.

14. Physical appearance: Elemental lead exists as a highly lustrous, heavy, silvery-grey metal with a cubic crystal structure that assumes a bluish tint as it tarnishes in air. It is quite soft and malleable. Several of its salts occur as variously coloured powders or liquids and are widely in industry and at home producing cumulative toxicity on chronic exposure.

15. Uses: Lead acetate(sugar of lead) has been used in therapeutics. Lead carbonate(white lead) is still used in paints. Lead oxide(litharge) is essential for glazing of pottery and enamel ware. Tetraethyl lead is mixed with petrol as an antiknock to prevent detonation in internal combustion engines. Lead tetroxide is the most common compound in vermilion(“ sindoor ”). Lead sulfide is used as a collyrium (“ surma ”).

16. SOURCES OF LEAD EXPOSURE: ENVIRONMENTAL DOMESTIC OCCUPATIONAL NON-OCCUPATIONAL Automobile exhaust Drug abuse Soil water Ceramic ware Colo u red picture books Contaminated flour Cosmetics “health “foods House paint Indigenous medicines Pencils Toys Auto repair works Battery making Glass manufacture Mining Plastics manufacture Plumbing Pottery Printing Rubber industry Ship building Smelting& refining Soldering(electronics Steel welding & cutting Candle with lead-containing wicks Ayurvedic medicines Paint Retained bullets ink Automobile storage battery casing Ceramic glazes Lead pipes Silvery jewellery workers Renovation / modernisation of old homes

17. Usual fatal dose: This is not relevant to lead since acute poisoning is very rare. The average lethal dose is said to be 10gm/70kg for most lead salts, while it is 100mg/kg for tetraethyl lead. TOXICOKINETICS: Lead is absorbed through all portals of entry. -Occupational exposure results mainly from inhalation, while in most other situations the mode of intake is ingestion -Tetraethyl lead can be absorbed rapidly through intact skin. Following absorption it is stored in the bones as phosphate and carbonate. In children about 70% of total body lead is skeletal, while in adults over 95% is in osseous tissues. Absorbed lead which is not retained in the body is excreted primarily in the urine(about65%) and bile (about 35%).

18. Mode of action: Lead combines with sulfhydryl enzymes leading to interference with their action. It decreases haeme synthesis by inactivating the enzyme involved such as aminolaevulinic acid dehydrase , aminolaevulinic acid synthetase , corporphyrinogen oxidase , and ferrochelatase . This results in anemia. Lead increases haemolysis as a result of which immature red cells are released into circulation such as reticulocytes and basophilic stipped cells. In CNS, lead causes oedema and has a direct cytotoxic effect leading to decreased nerve conduction, increased psychomotor activity,lower IQ, and behavioural disorders. Lead also has deleterious effects on the CVS (hypertension and myocarditis ), kidney(nephritis), and reproductive organs(infertility).

19. Clinical features: ACUTE POISONING: This is rare . Many reported cases of acute poisoning may be actually be exacerbations of chronic lead poisoning when significant quantities of lead are suddenly released into the bloodstream from bone. Symptoms include- metallic taste -abdominal pain - constipation or diarrhoea (black stool) - vomiting -hyperactivity or lethargy - ataxia - behavioural changes - convulsions - coma.

20. 2. CHRONIC POISONING: MILD TOXICITY (BL 40 -60 mcg/100ml ) MODERATE TOXICITY (BL 60-100 mcg/100ml) SEVERE TOXICITY (BL more than 100mcg/ml) Myalgia Paraesthesia Fatigue Irritability Abdominal discomfort Arthralgia Muscular exhaustibility Tremor Headache Diffuse abdominal pain Anorexia, metallic taste, vomiting Constipation Weight loss Hypertension Lead palsy: wrist or foot drop A bluish black lead line on gums Lead colic: severe abdominal cramps. Lead encephalopathy

21. DIAGNOSIS: Laboratory tests 1 . Whole blood lead levels: <10 μg / dL - normal in adults, no lower limit in children. >45 μg / dL - GI symptoms in adults and children. >70 μg / dL - high risk of acute CNS symptoms. >100 μg / dL - may be life-threatening. FBC - basophilic stippling of erythrocytes may be seen and features of a microcytic hypochromic anaemia such as a low MCV may be present. Sideroblasts may be seen. 2. Urine lead level: if this is above 150 mcg/ litre it is a significant finding, but it is unfortunately not reliable.

22. Renal function tests to detect renal complications and uric acid levels to detect gout may also be advisable. Nerve conduction tests should be considered if neuropathy is suspected. Psychometric testing should be considered if clinically indicated. Radio-imaging Plain X-ray may show transverse lines in tubular bones. These are actually areas of arrested bone growth and may persist for a long time after exposure ends. They are not seen in the early phase of exposure. Plain abdominal X-rays may show radio-opaque flecks in cases of suspected lead foreign body ingestion ( eg , pica in children). X-ray fluorescence works by detecting specific emissions from tissues when bombarded with X-rays. It is a sensitive method of detecting low levels of lead in the body. CT or MRI scan of the brain may be contributory in patients with symptoms suggestive of encephalopathy.

23. TREATMENT: 1.SEVERE ACUTE POISONING WITH ENCEPHALOPATHY: a. BAL -4mg/kg immediately (in children) b. Cranial CT scan: to rule out cerebral oedema Cerebral oedema managed by: Controlled hyperventillation , maintaining an arterial CO2 tension of 25-30 mmHg can reduce intracranial pressure. DIURETICS- Mannitol 20%- 1-1.5 gm/kg by infusion over 10-20 minutes(adult) ,0.5-1gm/kg by IV infusion(child) Glycerol- 0.3-1gm/kg orally. CORTICOSTEROIDS- Dexamethasone - 16mg/day in divided doses(low dose) & 1-2mg/day in divided dose(high dose).

24. c. For seizures: IV Diazepam ( Adult:up to 10mg slowly, repeat if necessary; Child: 0.-0.3mg/kg slowly). d. CaNa 2 EDTA 75mg/kg/day IV Infusion. e. After the initial dose of BAL, reapeat the same dose at 4 hourly itervals until blood level falls below 40 mcg/100ml.Then reduce BAL to 12mg/kg/day in 3 divided doses. f. Reduce CaNa 2 EDTA to 50 mg/kg/day as condition improves. - continue the above regimen until patient is asymptomatic and can tolerate oral chelation with D- penicillamine or DMSA.

25. 2. SEVERE ACUTE POISONING WITH ENCEPHALOPATHY: (BL more than 70mcg/100ml) BAL - 12 mg/kg/day. EDTA -50mg/kg/day. Discontinue BAL when the BL falls below 40mcg/100ml,but continue EDTA for 5 more days. Change to oral chelation subsequently which may have to be continued until the BL falls below 15mcg/100ml, or 3 months have been completed. 3.MODERATE POISONING: (BL level between 45 and 70 mcg/100ml) EDTA 50mg/kg/day. When blood lead falls below 40 mcg/100ml, begin oral chelation .

26. 4.MILD POISONING: BL level between20 and 35 mcg/100ml D- penicillamine 30 mg/kg/day in 3 divided doses. Start with ¼ th of the calculated dose. Double this after 1 week. Double again after 1 week. Continue this until the BL level falls to less than 15 mcg/100ml . 5. SUPPORTIVE MEASURES: Thiamine 10-50 mg/kg to improve neurological manifestation. Lead colic usually responds to Ivcalcium gluconate. Correct iron defficiency present. IV fluids Finally the sine qua non treatment of heavy metal poisoning.

27. REFERENCE: TEXTBOOK- MODERN MEDICAL TOXICOLOGY- VV PILLAI. THANK YOU…..