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Chapter: Modern Medical Toxicology: Chemical Poisons: Heavy Metals

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Lead - Chemical Poisons: Diagnosis

It has been suggested that all children should be screened for lead levels (BL) on their 1st birthday, and if possible at yearly intervals thereafter until they are 6 years old.

Diagnosis

·              It has been suggested that all children should be screened for lead levels (BL) on their 1st birthday, and if possible at yearly intervals thereafter until they are 6 years old. If at any time the BL is more than 20 mcg/100 ml, therapeutic intervention is indicated, and if it exceeds 70 mcg/100 ml, it should be treated as a medical emergency.

·              The current paediatric practice in the West is to first measure the free erythrocyte protoporphyrin before carrying out a blood lead quantification. Historically, the terms free eryth-rocyte protoporphyrin (FEP) and zinc protoporphyrin (ZnP) were used interchangeably, which is actually incorrect. The reason for this error was the inability to differentiate FEP from ZnP by the older techniques. Contemporary technology overcomes this, and both can be measured separately showing a normal ratio of 10 is to 9 between FEP and ZnP. Quantification of ZnP is generally perceived as one of the earliest and most reliable indicators of the impairment of haeme biosynthesis. But ZnP can be elevated in iron deficiency anaemia while the blood lead level is actually within normal limits. Hence when ZnP is raised, it is mandatory to confirm lead poisoning by performing a blood assay for lead level.

■■   While urine levels of aminolaevulinic acid (ALA) can also serve as a sensitive indicator of lead poisoning, ALA excretion rises only when blood lead concentrations exceed 40 mcg/100 ml.

   Laboratory tests for lead:

Blood

–  Complete blood count and peripheral smear—

General and non-specific findings include low haem-atocrit and haemoglobin values with normal total and differential cell counts. The peripheral smear may either be normochromic or hypochromic, and microcytic. Basophilic stippling is usually seen only in patients who have been significantly poisoned for a prolonged period. Hypochromia and basophilic stippling are strongly suggestive of lead intoxication, but their absence does not rule out lead poisoning. It must be borne in mind that such stippled RBCs may also be seen in arsenic and zinc poisoning.

– FEP and Znp levels (>50 mcg/100 ml)—An elevated FEP level indicates impairment of the haeme biosynthetic pathway and may result from lead poisoning or iron deficiency. In order to confirm whether it is due to the former, the BL must be estimated. Today ZnP levels are more commonly studied than FEP (vide supra). It is to be noted that both FEP and ZnP are not significantly elevated at lower levels of lead poisoning. In fact, the ability to reliably use zinc protoporphyrin levels as a screening tool to detect low blood levels is under serious question.

– Blood lead level (BL)—BL can change rapidly in response to lead intake (e.g. ingestion of lead paint chips). For short exposure periods, it usually has a linear relationship to intake levels. Blood lead levels reflect recent exposure or exposure over a period of up to 3 to 5 weeks. In individuals with high or chronic past exposure, BL usually under-represents the total body burden because most lead is stored in the bone and may be found at normal levels in the blood. However, during stressful circumstances, patients with a high body burden may have elevated BL because of the release of lead stored in bones.

--  The recommended methods of estimating blood lead level (BL) include atomic absorption spectroscopy (AAS), electrothermal atomic absorption spectroscopy (EAAS), anodic strip-ping voltammetry (ASV), inductively coupled plasma atomic emission spectroscopy (ICP-AES), and x-ray fluorescence spectroscopy.

Alternative methods include proton-induced x-ray emission (PIXE), fast neutron activation analysis (FNAA), mass spectrometry (MS), and microwave plasma detection. EAAS and ASV are the methods of choice. In recent years, ICP-AES has become the technique of choice owing to superior specificity and sensitivity. It provides highly accurate and rapid results.

Urine

–– The concentration of ALA in urine is widely used as a measure of lead toxicity in workers who are exposed occupationally. For this purpose colouri-metric methods were employed previously, but today fluorometry (after separation by HPLC) is preferred.

– Urine lead level : If this is above 150 mcg /litre it is a significant finding, but it is unfortunately not very reliable.

– Calcium disodium EDTA mobilisation test : This test is done mainly in children to find out whether a child whose BL is between 25 and 41 mcg/100 ml will respond to chelation therapy with a brisk lead diuresis. Children whose BL is more than 45 mcg/100 ml should not receive this provocative test; they should be referred for chelation therapy immediately.

-                Procedure:

»» First the patient is asked to empty the bladder. Then CaNa2 EDTA is administered at a dose of 500 mg/m2 in 5% dextrose infused over 1 hour. All urine must be collected with lead-free equipment over the next 8 hours. Preferably, urine should be voided directly into polyethylene or polypropylene bottles which have been cleaned in the usual way, then washed in nitric acid and thoroughly rinsed with de-ionised distilled water. For children who are not toilet trained, plastic paediatric urine collectors can be used. In the laboratory, the urine volume should be carefully measured and stored at 20° C until the lead concentra-tion is measured.

»» To obtain the total lead excretion (mcg), the concentration of lead in the urine (mcg/ml) is multiplied by total urinary volume (ml). The total urinary excretion of lead (mcg) is divided by the amount of CaNa2 EDTA given (mg) to obtain the lead excretion ratio.

»» An 8 hour CaNa2EDTA chelation provoca-tive test is considered positive if the leadexcretion ratio is more than 0.6 (though some clinicians use a cut-off of 0.5). Children with positive chelation test results should undergo a 5-day course of chelation.

– Urine porphyrin level: Patients with lead poisoning usually excrete elevated levels of porphyrins in the urine.

Bone

–– The x-ray fluorescence technique is brief and non-invasive and carries low-risk. It is based on the specific atomic property of lead to emit characteristic x-rays upon stimulation induced by external irradiation. The stimulated radiation is monitored externally by a solid state detector and can be expressed in terms of lead concentra-tion in the bone. Because emitted radiation is considerably attenuated by the overlying tissue, the tibial shaft is chosen as the measurement site because of its thin overlying skin. Calibration of the system can be done from a cadaver leg, and subsequent atomic absorption analysis from the same site. Published regression equations that could be used to estimate mean skeletal lead concentration of the entire body and also to predict the lead concentration are available. Many investigators now recommend such an “in-vivo analysis” of bone lead concentration as superior to the more cumbersome CaNa2EDTA chelationprovocative test.

–– Radiology: This involves evaluation of the ends of long bones for arrest of growth line, and of the abdomen for radiopaque densities. Radiological examination of the abdomen may show radiopaque foreign material, if the material has been ingested during the preceding 24 to 36 hours. The significant finding in bone is the appearance of dense transverse bands or lead lines extending across the metaphyses of the long bones, and along margins of flat bones such as the iliac crest. The width of the lead line varies depending upon the amount of lead ingested and the length of time it has taken. It usually takes 4 to 8 weeks of heavy exposure for dense bands to develop.

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