Toxicity Associated with Lead

At a Glance

Patients with lead poisoning usually present with nonspecific signs and symptoms, such as abdominal pain, constipation, irritability, difficulty concentrating and anemia. However, the symptoms vary depending on the age of the patient and the route and length of exposure. In acute lead toxicity, ataxia, mental confusion, nausea, and vomiting can be seen. In chronic toxicity, hypertension, arthralgia, abdominal pain, neuropsychiatric, and reproductive effects are more common.

All patients, particularly children, whether symptomatic or not, should be assessed for degrees of lead exposure. Lead is commonly found in the environment (e.g., air; soil; dust; drinking water; food, especially lead-soldered cans; paint; candle wicks; and batteries). The primary source of exposure for young children is usually not from eating lead paint chips, but from chronic ingestion and inhalation of lead-contaminated dust. Adults are usually exposed to lead because of their hobbies or occupations (e.g., battery manufacturing and recycling, smelting, welding, printing, glass-making, and stained glass work) with inhalation the most common route of entry.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Whole blood is the preferred specimen to assess recent lead exposure in adults, most commonly collected in a royal blue top tube containing EDTA anticoagulant. The correlation between whole blood lead concentrations and biological effects is the most known. Capillary blood lead samples are the preferred specimen for pediatric lead testing, because they are easier to obtain.

Lead diagnosis differs from other heavy metals in that screening asymptomatic children or those at risk for occupational or recreational exposure is recommended. The Centers for Disease Control (CDC) recommends action be taken in any child with lead concentrations greater than 10 mcg/dL. However, studies have shown an inverse relationship between concentrations below 10 mcg/dL and children’s IQs.

Typical reference ranges for lead depend on patient age. Ideally, children younger than 6 years of age should have lead less than or equal to 4 mcg/dL, whereas patients 7 years of age or older can tolerate levels less than 10 mcg/dL. Critical levels also vary with age, increasing from greater than 20 mcg/dL for patients 15 years of age or younger to greater than or equal to 70 mcg/dL for patients 16 years of age or older.

In symptomatic patients, elevated urine coproporphyrin, basophilic stippling, hypophosphatemia, and glycosuria are consistent with, although not specific for, lead toxicity. Lead flecks on abdominal radiograph and lead lines on long-bone radiographs can also be seen in children with significant lead burden.

Urine may be preferable to whole blood in monitoring occupational exposure as it is less invasive. A 24-hour urine should be obtained or the concentration should be normalized based on the creatinine value to adjust for different flow rates throughout the day. In addition, urine excretion rates can be used to monitor the effectiveness of chelation therapy.

The concentrations of lead in hair can be measured. The content of lead in hair is usually less than 5 mcg/g, with concentrations greater than 25 mcg/g indicating severe lead exposure.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Appropriate specimen collection is critical for all heavy metal testing. Tubes with metal caps or glued inserts affect test results. Surface contamination, insufficient collection volume, and inadequate mixing with EDTA can also result in inaccurate results and sample rejection.

Care must be taken when obtaining capillary blood samples from pediatric patients. Surface skin contamination can result in false elevations in lead levels if the health care provider does not use gloves, if the finger is not cleaned properly, or if the health care provider fails to wipe off the first drop of blood. All patients who have elevated capillary blood levels should have the result confirmed by obtaining a venous whole blood sample.

With hair specimens, external contamination is particularly problematic.

What Lab Results Are Absolutely Confirmatory?

Heavy metal toxicity can be confirmed if three factors are present:

a source of metal exposure is evident

the patient demonstrates signs and symptoms of toxicity with that metal

an abnormal concentration of that metal is present in blood, urine, or tissue

The definitive test for measuring lead is whole blood, because lead concentrates in erythrocytes. The most sensitive and specific methods to measure lead in biological fluids are atomic absorption spectrometry (AAS), anodic stripping voltammetry (AVS), and inductively coupled plasma-mass spectrometry (ICP-MS). Although AVS is the simplest to perform, it lacks sensitivity at the low end.

Repeated blood level measurements can be made to calculate a cumulative blood lead index (CBLI) in patients for which chronic low level exposure is a concern. CBLI is thought to closely parallel bone lead levels measured by X-ray fluorescence. Other nonlaboratory tests used to reflect cumulative lead exposure include neurobehavioral testing to assess cognitive function and nerve conduction velocity to assess peripheral neuropathy.

Isotopic variation can be exploited to determine the source of lead exposure (e.g., paint chips or soil).

Additional Issues of Clinical Importance

Lead (Pb) is an element with four stable isotopes (Pb 204, 206, 207, and 208). It is a cumulative poison that rapidly absorbs into bones and erythrocytes, distributes to all tissues, and, ultimately, deposits in bone, which serves as the reservoir to maintain tissue concentrations. The half-life of lead depends on the body compartment and renal function: typically 30 days for blood, 40 days for tissue, and more than 25 years for bone.

Children are more susceptible to the toxic effects of lead for several reasons:

They have a higher risk of exposure.
They have an incomplete blood brain barrier, which permits lead into the developing nervous system.
They adsorb a higher concentration of lead from the gastrointestinal (GI) tract.

Lead has multiple mechanisms of toxicity. Lead is an electrophile with high affinity for negatively charged sulfhydryl groups, leading to changes in protein structure. Cells in the central nervous system and kidney are particularly susceptible. By binding to sulfhydryl groups, lead inhibits one of the enzymes that catalyze heme synthesis, leading to anemia, and increase protoporphyrins in erythrocytes. Lead acts competitively with calcium and interferes with calcium dependent processes, which has been implicated as the mechanism for neurotoxicity. Lead also alters the permeability of the blood brain barrier, accumulates in astroglia, and promotes the generation of free radicals in endothelial and vascular smooth muscle cells, which may affect blood pressure.

Lead toxicity is treated by removing the source of exposure, supportive care, and chelation therapy with drugs, such as 2,3-dimercaptosuccinic acid.

Errors in Test Selection and Interpretation

In the absence of acute exposure, blood lead largely reflects the overall burden in the body. However, clinicians should be aware that more than 70% of the total body burden of lead, particularly in children, is contained in mineralized tissues, thus, blood lead level is not an accurate reflection of the total body burden.

Urine concentrations are not as useful as blood concentrations to assess lead toxicity, because lead is poorly excreted and found in lower concentrations in urine. Previously, urine lead testing was a component of the lead mobilization test. This test, which is no longer recommended, evaluated the increase in urinary lead concentration in response to a test dose of a chelating agent and predicted who would benefit from chelation therapy.

Serum or plasma lead levels are not appropriate to measure, because lead quickly absorbs into erythrocytes; therefore, lead concentrations in plasma and serum are only abnormal for a short period of time after exposure.

Measurement of lead levels in hair is also not ideal. In addition to the possibility of external contamination, hair levels do not correlate with blood concentrations and there is not well-accepted normative data, which makes interpretation difficult.

Free erythrocyte protoporphyrin (FEP) and zinc protoporphyrin (ZPP) both measure the effect of lead on hemoglobin synthesis. However, these tests are no longer indicated to screen for elevated lead levels, because only significant levels of lead will increase levels of FEP and ZPP.

High concentrations of gadolinium and iodine are known to interfere with most testing for heavy metals. If either gadolinium- or iodine-containing contrast media have been administered within 96 hours of specimen collection, results are not valid and should be repeated more than 96 hours after administration of a contrast media containing gadolinium or iodine.

If inductively coupled plasma-mass spectrometry (ICP-MS) is used to measure lead levels, care should be taken to sum the masses of 206, 207, and 208 to account for natural isotopic variation of lead in the environment.

False-positive results can be obtained when there is a significant interval between a screening test and a confirmatory test. Because of the 30 day half-life of lead, sporadic lead exposure may result in a true positive result on screening that has declined to a true negative by the time of confirmation.

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