Environmental Pathology - Metal : Lead Intoxication

Lead poisoning is mainly a pediatric problem related to pica, the habit of chewing on cribs, toys, furniture, and woodwork, and the eating of painted plaster and fallen paint flakes.

In adults occupational exposure to lead occurs primarily among those engaged in the smelting of lead, a process that releases metal fumes and deposits lead oxide dust in the industrial environment.

Lead oxide is a constituent of battery grids, and an occupational exposure to lead is a potential hazard in the manufacture and recycling of automobile batteries.

Accidental poisonings occasionally occur from the use of pottery that has been improperly fired with a lead glaze, the renovation of an old residence heavily coated with lead paint, or the "sniffing" of lead-containing gasoline.

It is still unresolved whether lead-containing automobile exhaust fumes contribute to clinically significant total body lead burdens, despite the clear lowering of mean blood levels since the introduction of unleaded gasoline.

Lead is absorbed either through the lungs or the gastrointestinal tract. Once in the blood, it rapidly equilibrates with the plasma and red cells. A portion of blood lead remains freely diffusible and enters either of two types of tissues. Bones, teeth, nails, and hair represent a tightly bound pool of lead that is not generally regarded as harmful.

By contrast, the amount of lead in the brain, liver, kidneys and bone marrow is directly related to its toxic effects.

With chronic exposure, 90% of the total body lead burden is in the bones. During metaphyseal bone formation in children, lead and calcium are deposited to produce the increased bone densities ("lead lines") seen radiographically at the metaphysis, thereby providing a simple method of detecting increased body stores of lead in children.

Lead is excreted by the kidneys.

Lead toxicity is manifested in the dysfunction of three important organ systems - the nervous system, the kidneys, and the hematopoietic system.

The central nervous system is the target of lead toxicity in children.

Adults usually present with manifestation of peripheral neuropathy.

Children with lead encephalopathy are typically irritable and ataxic.

They may convulse display altered states of consciousness, from drowsiness to frank coma.

Children with blood lead levels 80 microgm Pb/ml but with concentrations lower than those in children with frank encephalopathy (120 microgm Pb/ml), exhibit mild central nervous system symptoms such as clumsiness, irritability, and hyperactivity.

In lead encephalopathy, the brain is edematous and displays flattened gyri and compressed ventricles.

There may be herniation of the uncus and cerebellar tonsils.

Microscopically, congestion, petechial hemorrhages, and foci of neuronal necrosis are seen. A diffuse astrocytic proliferation in both the gray and white matter may accompany these changes. Vascular lesions in the brain are particularly prominent with dilatation and proliferation of capillaries.

The most common manifestation of lead neurotoxicity in the adult is a peripheral motor neuropathy, typically affecting the radial and peroneal nerves and resulting in wrist and foot drop, respectively. Lead-induced neuropathy is probably also the basis of the paroxysms of gastrointestinal pain known as lead colic.

Lead intoxication also produces an anemia by disrupting heme synthesis in bone marrow erythroblasts through inhibition of delta-aminolevulinic acid dehydrogenase, the second enzyme in the de novo synthesis of heme, and through inhibition of ferrochelatase, the enzyme that catalyzes the incorporation of ferrous iron into the porphyrin ring. The resulting inability to produce heme adequately is expressed as a microcytic and hypochromic anemia resulting that seen in iron deficiency, where heme synthesis is also impaired. The anemia of lead intoxication is also characterized by prominent basophilic stippling of the erythrocytes, related to the clustering of ribosomes.

The life span of the red blood cells is decreased , thus the anemia of lead intoxication is due to both ineffective hematopoiesis and accelerated turnover.

Lead is toxic to the proximal tubular cells of the kidney. The resulting dysfunction is characterized by aminoaciduria, glycosuria and hyperphosphaturia (Fanconi's syndrome).

Such functional alterations are accompanied by the formation of inclusion bodies in the nuclei of the proximal tubular cells. These inclusions are characteristic of lead nephropathy and are composed of a lead-protein complex containing more than 100 times as much lead as in the whole kidney.

Lead poisoning is treated with chelating agents such as calcium EDTA, either alone or in combination with dimercaptopropanol (BAL).

Both the hematologic and renal manifestations of lead intoxication are usually reversible. The alterations in the central nervous system are generally irreversible.

Lead Poisoning in an Adult: Lead Mobilization by Pregnancy?J Gen Intern Med. 2007 Jun 12;

We report a case of acute lead poisoning in an adult female who had last been exposed to lead 7 years ago. She presented with abdominal pain, knee pain, and neurological symptoms, hypertension, chronic kidney disease, and anemia with basophilic stippling and lead gum lines. Compared to during her recent pregnancy, her lead level had almost tripled in 5 months to 81 mcg/dL. Chelation therapy was initiated and improved the patient's symptoms and lead level significantly. In the absence of any new lead exposure or other reasons for increased bone turnover, this acute lead increase was likely due to skeletal mobilization caused by increased resorption from mineralized tissue during and after her pregnancy. This case report illustrates the seriousness of long-term health effects associated with lead poisoning at a multi-organ level, even years after the initial exposure. Thus, patient care should not be limited to the acute treatment of increased lead levels, but also include prevention of increased mobilization and bone turnover and appropriate patient education. In this context, we review various aspects of lead toxicity, especially during pregnancy and lactation.

Mechanisms and toxic effects of lead on the cardiovascular system.Med Pr. 2006;57(6):543-9.

Exposure to lead is still one of essential health problems in our country. Current views on mechanisms and toxic effects of lead on the cardiovascular system are presented. Special attention is paid to changes in the heart morphology and physiology resulting from long-term exposure to lead, the effect of lead on the muscular coat and endothelium of blood vessels, changes in the metabolism of erythrocytes, leukocytes and thrombocytes in persons chronically exposed to lead as well as to the relation between lead and hypertensive and atherosclerotic illnesses induced by changes in the structure and function of the cardiovascular system. The described effects of lead exposure should encourage us to further reduction of occupational and environmental exposure to this metal and controversies that still exist to continue research in this field.

The politics of lead toxicology and the devastating consequences for children.Am J Ind Med. 2007 May 7;

At virtually every step in the history of the uncovering of lead's toxic qualities, resistance was shown by a variety of industrial interests to the association of lead and toxicity. During the first half of the last century, three primary means were used to undermine the growing body of evidence: first, the lead industry sought to control lead research by sponsoring and funding university research. In the 1920s, the General Motors Company, with the aide of DuPont and Standard Oil Companies, established the Kettering Labs, a research unit at the University of Cincinnati which, for many decades was largely supported by industry funds. In the same decade, the lead industry sponsored the research of Joseph Aub at Harvard who worked on neurophysiology of lead. A second way was to shape our understanding of lead itself, portraying it as an indispensable and healthful element essential for all modern life. Lead was portrayed as safe for children to use, be around, and even touch. The third way that lead was exempted from the normal public health measures and regulatory apparatus that had largely controlled phosphorus poisoning, poor quality food and meats and other potential public health hazards was more insidious and involved directly influencing the scientific integrity of the clinical observations and research. Throughout the past century tremendous pressure by the lead industry itself was brought to bear to quiet, even intimidate, researchers and clinicians who reported on or identified lead as a hazard. This article will draw on our previous work and add new documentation of the trajectory of industry attempts to keep out of the public view the tremendous threat of lead poisoning to children.

Recommendations for medical management of adult lead exposure.Environ Health Perspect. 2007 Mar;115(3):463-71.

Research conducted in recent years has increased public health concern about the toxicity of lead at low dose and has supported a reappraisal of the levels of lead exposure that may be safely tolerated in the workplace. In this article, which appears as part of a mini-monograph on adult lead exposure, we summarize a body of published literature that establishes the potential for hypertension, effects on renal function, cognitive dysfunction, and adverse female reproductive outcome in adults with whole-blood lead concentrations < 40 microg/dL. Based on this literature, and our collective experience in evaluating lead-exposed adults, we recommend that individuals be removed from occupational lead exposure if a single blood lead concentration exceeds 30 microg/dL or if two successive blood lead concentrations measured over a 4-week interval are > or = 20 microg/dL. Removal of individuals from lead exposure should be considered to avoid long-term risk to health if exposure control measures over an extended period do not decrease blood lead concentrations to < 10 microg/dL or if selected medical conditions exist that would increase the risk of continued exposure. Recommended medical surveillance for all lead-exposed workers should include quarterly blood lead measurements for individuals with blood lead concentrations between 10 and 19 microg/dL, and semiannual blood lead measurements when sustained blood lead concentrations are < 10 microg/dL. It is advisable for pregnant women to avoid occupational or avocational lead exposure that would result in blood lead concentrations > 5 microg/dL. Chelation may have an adjunctive role in the medical management of highly exposed adults with symptomatic lead intoxication but is not recommended for asymptomatic individuals with low blood lead concentrations.

Lead in paint: three decades later and still a hazard for African children?Environ Health Perspect. 2007 Mar;115(3):321-2. Epub 2006 Dec 14

BACKGROUND: Surveys undertaken in South Africa have shown that a large proportion of children are exposed to lead from a variety of sources. OBJECTIVES: The overall objective of this work was to examine, through a series of small-scale investigations, the role of lead-based paint in the blood lead distribution of South African children. DISCUSSION: We suggest that the African public health community strengthen their efforts to prevent lead poisoning in African children through a holistic approach that includes the promulgation and enforcement of appropriate legislation as well as research to identify further sources of exposure to lead.

Anaemia and abdominal pain due to occupational lead poisoning.Haematologica. 2007 Mar;92

We describe a 47-year-old patient with chronic anaemia with basophilic stippling of erythrocytes, recurrent abdominal colics, discoloration of gums, sensitive polyneuropathy to the four limbs, hyper- uricaemia, hepatosteatosis with raised transami- nases, and a long ignored history of lead exposure in a battery recycling plant. The diagnosis of poi- soning was confirmed by high lead levels in the blood and urine, decreased erythrocyte delta- aminolevulinic acid dehydratase (ALA-D), raised erythrocyte zinc protoporphyrin (ZP), and elevat- ed urinary excretion of porphyrins. Chelation with EDTA resulted in increased urinary lead excretion, gradual improvement of the clinical picture, and progressive normalization of lead biomarkers. The case highlights the importance of occupational anamnesis for the diagnosis of lead poisoning, an uncommon condition which may mimic a variety of internal and surgical diseases. Since antiquity, lead has been extensively mined, produced, and utilized in a variety of industrial settings, such as metallurgy, construction, production of plastics, ceramics, paints and pigments.1-3Lead and its com- pounds are systemic toxicants, and a wide range of adverse health effects (including haematological, gastrointestinal, neuropsychiatric, cardiovascular, renal, endocrine, and reproductive disorders) has been observed in exposed workers.1,4,5The general population (particularly children) may also be exposed to toxic lead levels due to air, soil, food and water contamination.1,4,6 Thanks to the improvement of workplace hygienic conditions, the pathological picture of occupational lead poisoning (plumbism, saturnism) has gradually become less serious, at least in the most industri- alized countries, and has progressively changed into aspecific, subclinical manifestations.1, 5, 7 We describe here an unusual case (nowadays) of anaemia and recurrent abdominal pain due to lead poisoning from batteryrecycling.

Encephalopathy and cerebellar calcifications from lead poisoning.Presse Med. 1990 May 26;19(21):997-1000.

In a male and female couple hospitalized the former for exploration of a painful abdominal syndrome with encephalopathy, the latter at the end of an epileptic attack, the presence of cerebellar calcifications in unusual locations led to the demonstration of a domestic lead poisoning of dietary origin. The problems raised by the laboratory diagnosis and the inadequacy of static assays are underlined; in some cases, the EDTA test was the only means to confirm the toxicity. The arguments in favour of a relation between lead poisoning and cerebellar calcifications are developed.