Lead - Forensic & Toxicology PDF

Lead - Forensic & Toxicology 071 Lead 1 Introduction Sources Occupational Manufacturing of ammunition, batteries, paints, pipe so...

Lead - Forensic & Toxicology 071 Lead 1 Introduction Sources Occupational Manufacturing of ammunition, batteries, paints, pipe solder, Ceramic. Mining and extracting lead. Non-occupational Water supply. Automotive exhaust, house dust, paint dust, flakes. Newspapers lead glazed pottery and lead crystals. Toxic compounds Uses Lead sulphide (least toxic) Applied on the eyes (kohl) Lead carbonate Manufacture of paints Lead tetraoxide Paints, lead glasses, battery Tetraethyl lead Antiknock for petrol (gasoline) 2 Mechanism of toxicity Local Irritation at the site of absorption. Remote CNS: deleterious effects on the nerve cells and myelin sheaths and By Dr amro ashraf  ‫ﺣﻠﻮة‬-‫دﻋﻮة‬-‫اﻟﺨﺪﻣﺔ‬-‫ﺗﻤﻦ‬# 072 Semester-5 causes cerebral edema. Renal: Proximal renal tubular dysfunction. Hemoglobin synthesis: combines with sulfhydryl group of ptns causing impaired function of enzymes important for hemoglobin synthesis. ñ Fragility of RBCs. Defective heme synthesis. Disturb Calcium metabolism. 3 Clinical Picture Acute (relativity rare) Local GIT: nausea, vomiting, cramping abdominal pain, constipation, Metallic taste, dry throat, thirst. Remote ❶ GIT: Toxic hepatitis. ❷ CNS: Headache, lethargy, insomnia, paresthesia. Lead encephalopathy. It is commonly preceded by several weeks of prodromal complaints, including increasing irritability, headache and sleep disturbance. Encephalopathy characterized by ataxia, seizures, delirium, stupor and coma. ❸ CVS: Hemolytic anemia. Chronic Low levels may be associated with subclinical effects as impairment of visual- motor dexterity, reaction time and slowing of motor nerve conduction velocity. Facial pallor: Earliest sign around the mouth, due to vasospasm and produced by contraction of the capillaries at the arterial side. By Dr amro ashraf  Lead - Forensic & Toxicology 073 Hematological effect: ❶ Hypochromic anemia with normocytic or microcytic indices. ❷ Reticulocytosis due to anemia ❸ Punctuate basophilia (basophilic stippling of erythrocytes): early sign as consequences of lead-induced inhibition of pyrimidine-5 nucleotidase or cellular ribonucleases. GIT: ❶ Burton’s/Burtonian (lead line) In 50-70% cases, a stippled blue line on the gingival surface due to sub- epithelial deposit of granules at the junction of teeth, especially near dirty or carious teeth. It is due to formation of lead sulphide (reaction of circulating lead+ sulfur ions released by oral microbial activity) especially near dirty or carious teeth. Seen in poisoning with copper, iron. ❷ Colic In 85% cases. The pain is spasmodic, paroxysmal, occurs at night may be very severe. Pain is slightly relieved by application of pressure over the abdomen. ❸ Constipation Neurological effect: ❶ Deficits in cognitive function, IQ decreased and attention impairment especially in children. ❷ Irritability, fatigue, headache, sleep disturbance and depressed mood. ❸ Lead palsy (peripheral neuropathy: mainly motor) It is a late and uncommon phenomenon. There may be tremors and cramps before the actual muscle weakness. Later the extensor muscles of wrist (Wrist drop) and anterior tibial muscles (foot drop) are affected. It may occur in male adults' workers exposed chronically to high lead levels. ❹ Lead encephalopathy: Symptoms include changes in personality, restlessness, hyperkinetic and aggressive behavior disorders, mental dullness, learning disorders, refusal to play, headache and insomnia. Reproductive system effects: ❶ In males: ↓ sperms &loss of libido. ❷ In females: ↑ incidence of menstrual irregularities, abortion & still birth. ❸ Fetus: lead can pass to developing fetus affecting its CNS (the most By Dr amro ashraf  ‫ﺣﻠﻮة‬-‫دﻋﻮة‬-‫اﻟﺨﺪﻣﺔ‬-‫ﺗﻤﻦ‬# 074 Semester-5 susceptible). Effects on the eye: ❶ Optic atrophy in severely intoxicated patients. ❷ Retinal stippling noticed by ophthalmoscope with grayish glistening lead particles, in the early phase of chronic lead poisoning. Cardiovascular effects: Hypertension (vasoconstriction) Renal effects: ❶ Interstitial nephritis. ❷ Renal insufficiency. ❸ ò Renal clearance of uric acid. ❹ Fanconi-like syndrome (aminoaciduria, glucosuria, hypophosphatemia, hyperphosphaturia). Bones: Osteopathy in children and young adults, it is deposited beyond the epiphysis of growing long bones leading to abnormal development. Carcinogenic effect: Lead is considered a probable human carcinogen. Clinical presentation of lead toxicity (listed in approximate order of appearance). 4 Laboratory Blood lead level: is the single most useful lab. Test, normal level in adult < 10 µg/dl, and children < 5µg/dl. Liver and kidney function tests. Radiological: Radio-opaque bands or lead lines at the metaphyseal plate of long bones. (hyperdense deposits of Ca because inhibition of calcified cartilage resorption seen in children 2-6 years). Opaque material may be seen in X-ray of stomach and intestines. Complete blood count (CBC) Microcytic hypochromic anemia punctuate basophilia and reticulocytosis. By Dr amro ashraf  Lead - Forensic & Toxicology 075 Why children are more vulnerable to develop lead poisoning? Children < 3 years are at the greatest risk for lead poisoning ❶ As they are more likely to put things containing lead into their mouths (pica: persistent eating of non-nutritive material for 1 month or more) & their brains are yet developing ❷ children absorb up to 70% while adults about 20%. ❸ Often undetected, no obvious symptoms. With continuous exposure, lead accumulates over months & years & cause serious health problems e.g Learning disabilities. Behavioral problems. Developmental delay & malformed bones. 5 Treatment Emergency Maintain airway, breathing & circulation. Decontamination ❶ Remove the patient from the source ❷ Gastric lavage and whole bowel irrigation and cathartics ❸ Consider surgical removal of lead bullets, shrapnel, or pellets located in or adjacent to synovial space. Antidotes (chelation therapy) Edetate calcium disodium: (CaNa2EDTA) as 30 mg/kg/day in 4-6 divided doses or as a continuous infusion for 5 days. Prolonged dosing has risk of nephrotoxicity. By Dr amro ashraf  ‫ﺣﻠﻮة‬-‫دﻋﻮة‬-‫اﻟﺨﺪﻣﺔ‬-‫ﺗﻤﻦ‬# 076 Semester-5 BAL (British Anti-Lewisite, dimercaprol): An oily solution. The most effective in preventing renal damage if administrated within 4 hours after acute ingestion of lead salts. Dose 3-5 mg/kg IM every 4-6 hours for 3 days. Side effects: HTN, nausea, vomiting, headache, pain at the injection sites, priapism and convulsions. Succimer (dimercaptosuccinic acid DMSA) oral, IM, IV: In severe acute poisoning 3-5 mg/kg every 4 hours by IV infusion over 20 min in the first day then continue orally In chronic poisoning 10 mg/kg orally every 8 h for 5 days, Every 12 h for 2 weeks. For asymptomatic patients: Children with blood lead concentration ≥ 45 µg/dl and Adults > 80-100 µg/dl administer oral succimer. There is no consensus regarding the value of chelation at lower levels. Enhanced elimination There is no role for enhanced elimination. Symptomatic treatment ❶ Calcium chloride 5 mg as 10% solution IV or calcium gluconate 10 ml of 10% solution IV causes deposition of lead in bones from blood to combat acute crisis. ❷ Peritoneal or hemodialysis in anuric patients with chronic renal failure. ❸ Correction of dietary deficiencies in iron, calcium. ❹ Ammonium chloride 1g, 3-4 times given daily. So, the lead deposited in the bones are mobilized to the blood and extracted. ❺ Physical therapy and/or cognitive rehabilitation therapy for treatment of significant neurotoxic sequelae. By Dr amro ashraf