Lead poisoning has been known since ancient times, originally as a result of exposure to fumes arising from the lead smelting process. The industrial revolution led to a vastly increased prevalence and a renewed awareness of adult lead poisoning. Early industrial workers with tetraethyl lead became psychotic and died of lead poisoning but this was thought to be a problem only with high levels of exposure.

The automobile age brought with it the introduction of leaded gasoline. Once lead from auto emission enters the environment it is there indefinitely and could consequently contaminate the soil and water, though some researchers assert that incinerator emissions, rather than leaded gasoline, were largely responsible for increased airborne lead. In addition to posing a threat to human health, acute lead toxicity can produce detrimental effects on eco-systems. Lead perturbs multiple enzyme systems. As in most heavy metals, any ligand with sulfhydryl groups is vulnerable. These effects include low growth rates in plants; developmental, reproductive and nervous system problems in mammals, birds, and fish; and, in severe cases, death. Lead is highly toxic to aquatic life, particularly in soft water. Since lead bioaccumulates in the tissues of living organisms, it can result in secondary toxicity in animals and humans at the top levels of the food chain.

Lead is a natural compound that exists in elemental, inorganic, and organic forms. Inorganic lead is absorbed from the lungs or gastrointestinal tract. In adults, the most significant route of absorption is respiratory tract with an average absorption rate of approximately 40 percent. Activities such as scraping and sanding of leaded paint from surfaces, as well as various burning and smelting processes, can cause respiratory exposure to inorganic lead.

Children differ physiologically from adults and the effects of exposure differ accordingly. The most important route of exposure in children is the gastrointestinal tract. Because of their small body sizes and their rapid development, children are more vulnerable than adults to the hazards of lead exposure. Children between one and two years of age absorb 40 to 50% of ingested lead, whereas adults absorb only 10 to 15% of ingested lead. The rate of absorption is increased when diets are deficient in iron, calcium, zinc, and phosphate.

In developing countries, where leaded gasoline, leaded paint, and other major exposure routes are still common, all children under age two and more than 80 percent between the ages of three and five may have blood lead levels that exceed the World Health Organization (WHO) standard. It is estimated that 15 to 18 million children in economically developing countries may have suffered permanent damage from lead poisoning, resulting in lowered intelligence (as measured by IQ tests), learning disabilities, hearing loss, reduced attention span, and behavioral abnormalities.

Organic (tetraethyl) lead that is found in gasoline can be absorbed via the skin. After absorption, 99% of lead in circulation is bound to erythrocytes and only one percent is free. The main route of excretion is through urine. The skeletal system contains 95% of the body burden of lead with a half-life that approaches decades. Conditions such as pregnancy, menopause, breast-feeding, hyperthyroidism, or any hypermetabolic states could increase the bone turnover and consequently the plasma lead levels.(1),(2),(3)

Occupational exposure is the main reason for adult lead poisoning. Workers who are at particular risk of such hazardous exposures to lead include welders, iron cutters, abrasive blasters, painters, laborers, renovation and remodeling contractors, people who work at firing ranges, and those who are involved in the manufacture and disposal of car batteries and the maintenance and repair of bridges, water towers, and other steel structures.

Lead poisoning can cause many non-specific signs and symptoms and sometimes comes to the attention of a hematologist because of anemia. There are many case reports of lead poisoning from retained bullets (inorganic lead) and increasing blood lead levels over time have been documented, especially when a gunshot wound is accompanied by a fracture.(4),(5),(6),(7),(8) Despite this, retained bullets are routinely left in place if there is no immediate need for their removal.(9)

We present an instructive case of lead poisoning to further emphasize the burden of this disease and the need for careful assessment of the adult with potential lead toxicity.

The initial workup by his primary care physician revealed a microcytic anemia (Hgb 9.6 g/dL, Hct 27.4%, MCV 78). The patient was referred to a gastroenterologist for upper and lower GI endoscopy in order to find any possible site of GI bleeding that might be the cause of his microcytic anemia. No abnormalities were found. The results of the ultrasound and CT-scan of the abdomen to investigate any other possible intra abdominal process that could explain the colicky pain were inconclusive.

On the basis of the association of abdominal pain and anemia, a blood lead level was measured and was 163 mcg/dl (normal <5 mcg/dl). The patient worked as a bricklayer and lived in a 100-year-old house near a police shooting range. Investigation of materials used at his job, as well as his household water, found no source of lead. The patient was admitted to the hospital because of refractory abdominal pain and treatment for plumbism.

Physical examination at the hospital revealed a well-nourished white male. The conjunctivae were pale. The sclerae were anicteric. The oral mucosa was normal and there was gray discoloration of the gums. There was no cervical lymphadenopathy. There was a soft systolic flow murmur at the left sternal border. The abdomen was soft, without tenderness or hepatosplenomegaly. There was no edema or cyanosis of the extremities. Neurologic exam revealed intact cranial nerves and no focal motor or sensory deficits. The deep tendon reflexes were normal and there were no signs of peripheral neuropathy.

Treatment

Treatment was started with dimercaprol (BAL) 500 mg by deep IM injection, followed by 300 mg every 4 hours. Calcium EDTA 2 gm by intravenous infusion over 12 hr once daily was given concurrently. On the second hospital day, the patient's abdominal pain became worse. It was believed that the cause of the worsening abdominal pain was probably secondary to treatment with BAL and EDTA, causing mobilization of lead into the blood. X-rays showed a bullet in the right pelvis near the right pelvic ramus and prostate. There were also bullet fragments in the right lower leg.

On the third hospital day, the patient's symptoms gradually improved with simultaneous decline in the blood lead level to 60 mcg/dl. On the fifth hospital day, the patient developed a red, warm left great toe, which was painful to touch, with no decrease in range of motion. The patient was treated with colchicine with improvement of his symptoms. His blood lead level prior to discharge was 53 μg/dl. An urologist was chosen for the surgical removal of the bullet because of the location near the prostate. The multiple bullet fragments in the leg were too small and numerous for easy removal.

The patient remained asymptomatic and was seen for follow-up as an outpatient. The blood lead level rose to 86 mcg/dl and oral succimer (dimercaptosuccinic acid, Chemet^®) was administered for two weeks, which resulted in a decrease of the blood lead level to 29 mcg/dl. Two subsequent cycles of succimer were given with the patient remaining asymptomatic.

Implications and Discussion

The present clinical case emphasizes the importance of lead poisoning as a possible diagnosis for severe abdominal pain and anemia. Occupational sources are the most common cause of elevated blood lead levels, but retained bullets must also be considered as a possible source of exposure to lead.(10) Despite the absence of symptoms in the majority of patients carrying lead bullet fragment in their bodies, numerous case reports have demonstrated that lead poisoning, with potentially fatal consequences, can result from retained lead projectiles.(4),(5),(6),(7) This is particularly important when these fragments are located in close vicinity of the large joints like knees, hips and shoulder.(8),(9),(12) The epidemic of violence by gunfire may result in increasing numbers of lead poisoning cases from this exposure. The interval between lodging of the bullet and clinical evidence of lead poisoning has ranged from two days to 40 years.(10),(11)

The major toxic effects of lead are referable to the abdomen, blood, and nervous system. Our patient presented with colicky abdominal pain and anemia.(1) The exact pathogenesis of lead colic is not clear.(17) This pain may be confined to various locations and simulate a variety of surgical and non-surgical conditions.

Anemia is a frequent finding in lead poisoning and could be normocytic and normochromic but usually is microcytic and hypochromic.(2) Several enzymes of heme synthesis are inhibited, including δ-aminolevulinic acid (ALA) synthetase, ALA dehydrase, heme synthetase, porphyrinogen deaminase, uroporphyrinogen decarboxylase, and coproporphyrinogen oxidase. The interference with the red cell enzymes results in basophilic stippling.(2)

Lead also interacts with essential cations, particularly calcium, iron, and zinc; it interferes with the sodium-potassium-adenosine triphosphate (Na⁺/K⁺-ATP) pump; and it alters cellular and mitochondrial membranes, thereby increasing cellular fragility. Additionally, lead inhibits pyrimidine-5-nucleotidase and alters other nucleotide functions.(3)

Genetic polymorphisms, such as variants of the gene that codes for aminolevulinic acid dehydratase or the C282Y hemochromatosis gene, may confer differences in susceptibility to lead toxicity.(1),(2)

Early central nervous system symptoms are vague and are often overlooked. These manifestations include sleep disturbances, restlessness, lethargy, memory loss, and irritability. Wristdrop, footdrop, and peripheral neuropathy are more common in adults than children.(1) The subtle changes in cognition and concentration can occur at lower blood lead levels and this underscores the importance of early diagnosis and careful assessment of this potential disastrous disease.(3)

Involvement of other organs such as the kidney (diffuse interstitial fibrosis), cardiovascular (hypertension) and liver has been reported.(1) Chronic hyperuricemia with an increased risk of gout has been reported in literature and, as mentioned earlier, our patient developed gout during the course of treatment with chelating agents.(1)

The most important test for diagnosing lead toxicity is the blood lead level. The other tests that measure lead effects are the free erythrocytes protoporphyrin (FEP) and zinc protoporphyrin (ZPP). Increased amounts of δ-aminolevulinic acid and coproporphyrin are found in the urine.(2),(3)

It is absolutely essential to eliminate the source of intoxication or prevent further exposure. Chelating agents that form tight complexes with lead and thus promote its biologic inactivation and elimination from tissues include edetate calcium disodium (CaEDTA), dimercaprol (BAL), succimer (Chemet^®) and penicillamine.(3) In our case, because of severity of the symptoms and critically high levels of lead, we managed our patient with both CaEDTA and BAL, which produced efficacious decline in lead levels and improvement in the patient's symptoms. Because most of the body lead level is stored in the bones, clinical improvement and reduction in blood lead levels may be temporary and must be followed by frequent blood lead level measurements and clinical correlations.(10),(11),(16)

Conclusion

Lead poisoning can present with non-specific signs and symptoms. Prompt attention and early intervention can avoid irreversible damage to nervous system and other body organs. References to previous publications in term of incidence of lead poisoning after gunshot wounds are controversial. Physicians should be particularly alert in screening for elevated lead levels in people with retained bullet fragments.(4),(6),(7) This is particularly true when fragments are in contact with body fluids capable of solubilizing lead.(10),(11),(12),(13)