Lead Poisoning Case Study

Lead Poisoning Case Report

• A 66-year-old man, employed in a secondary lead smelter for 44 years, had a geometric mean air lead concentration of 0.26 mg/m³ at his work sites.
• The patient complained of headaches but denied vomiting, abdominal pain, constipation, loss of appetite, irritability, fatigue, or loss of muscular coordination.
• No objective symptoms of pallor, clouding of consciousness, or tetraparesis (paralysis of extensor muscles with atrophy) were observed.
• Blood lead levels: 66.4 µg/dL (normal, <20 µg/dL).
• Urinary lead: 114 µg/24 hours (normal, <80 µg/24 hours).
• Urinary 6-aminolevulinic acid (ALA): 18.3 mg/24 hours (normal, 1-7 mg/24 hours).
• Protoporphyrin in blood: 583 µg/dL (normal, 15-100 µg/dL) of erythrocytes.
• Hemoglobin: 12.6 g/dL (normal, 13.5-17.6 g/dL).
• Kidney functions: urinary protein, trace (normal, <30 mg/dL); blood urea nitrogen, 25 mg/dL (normal, 8-20); serum uric acid, 5.9 mg/dL (normal, 3.6-7.6); serum creatinine, 1.1 mg/dL (normal, 0.7-1.3).
• Urinary N-acetyl-B-D-glucosaminidase (NAG) activity 7.0 U/L (normal, <5.0); urinary B2-microglobulin, 92 µg/L (normal, 20-600); urinary a₁-microglobulin 9.5 mg/L (normal, 0.5-6.0).
• Effects on the central and peripheral nervous systems unclear but effects on heme biosynthesis evident.
• Hemoglobin levels decreased below normal due to lead exposure.
• Renal proximal tubular damage was evident by increased urinary NAG activity and a₁-microglobulin excretion.
• The worker was exposed to higher air lead concentrations than the TLV of 0.15 mg/m³ recommended by ACGIH (1993).
• Reducing lead exposure by improving the occupational environment/industrial process is the most important treatment.
• The worker's protective mask for dust was insufficient.

Lead Poisoning Diagnosis

• Acute encephalopathy with renal failure and severe gastrointestinal symptoms can develop in children who ingest lead-based paint chips.
• Subclinical lead intoxication is dangerous to children because symptoms may be absent.
• Occupational exposure leads to slower lead absorption over weeks or months, resulting in a subacute or chronic clinical course.
• Absorbed lead is toxic to the central nervous system, peripheral nervous system, heme biosynthetic pathway, kidneys, reproductive system, and gastrointestinal system.
• Air lead concentration measurement in the workplace is useful for evaluating lead exposure.
• TLV of lead as 0.15 mg/m³ is recommended by ACGIH.
• Blood lead levels and symptoms from physical exams are reliable indicators of current lead exposure.

Lead Mobilization Test

• Calcium disodium ethylenediaminetetraacetic acid (CaNa₂EDTA) forms chelate complexes with heavy metals.
• The amount of lead excreted after CaNa₂EDTA administration determines the outcome of the provocative chelation test.
• The lead mobilization test is used for children with initial confirmatory blood lead levels of 25 to 44 µg/dL, and for adults after cessation of lead exposure, where non-specific symptoms appear.
• Procedure: the patient empties the bladder, CaNa₂EDTA is infused over one hour at a dosage of 500 mg/m² of body surface in 5% dextrose.
• An 8-hour CaNa₂EDTA mobilization test is considered positive if the lead excretion ratio is >0.6.

Central Nervous System

• Manifestations of lead neurotoxicity are age and dose-dependent.
• Acute encephalopathy is associated with blood lead levels exceeding 150 µg/dL
• Subencepalopathy is associated with prolonged elevation of lead levels above 80 to 100 µg/dL.
• Children's nervous systems are more sensitive than adults'.
• Early neurotoxicity signs include memory and attention deficits, including lower IQ scores.

Peripheral Nervous System

• Polyneuropathy is more severe in motor nerves than sensory nerves.
• Lead targets motor axons, causing axonal degeneration and segmental demyelination.
• Subclinical neuropathy, is occasionally seen at blood lead levels above 30 to 40 µg/dL.

Heme Synthesis and Hematological Effects

• Anemia from impaired heme synthesis is generally observed at blood lead levels above 80 µg/dL
• Reduced hemoglobin production occurs at over 50 µg/dL
• Presence of basophilic stippled erythrocytes is associated with severe anemia with iron deficiency.
• Increased urinary ALA and elevated coproporphyrins are observed at lead concentrations are more than 40 µg/dL.
• Zinc protoporphyrin (ZPP) elevation is observed at blood lead levels greater than 20 µg/dL.
• Decreases in ALA dehydratase and Py-5-N activities are associated with blood lead levels above 10 to 15 µg/dL.

Renal Effects

• Effects of lead on the renal proximal tubule have been observed with manifestations of the Fanconi syndrome.
• Intranuclear inclusion bodies that contain high lead concentrations are observed in the biopsy of renal tubular cells from exposed workers.
• Increases of NAG activity and a₁-microglobulin in urine reflect proximal tubular damage or dysfunction and are occasionally seen when blood levels of lead exceed the 20 to 40 µg/dL range.
• Chronic forms of end-stage renal disease and renal failure with gout or hypertension follow many years of excessive lead exposure.

Reproductive System

• Lead is associated with increases in spontaneous abortion, stillbirth, and infant mortality.
• Women aged less than 45 years should not engage in work that would entail lead exposure and should strive to keep their blood lead levels below 10 µg/dL.
• In males, a decrease in sperm count and an increase of abnormal sperm occur with lead intoxication.

Gastrointestinal Systems

• Lead colic (severe abdominal pain) and sporadic vomiting are observed in acute intoxication with blood lead levels >100 µg/dL.
• Lead-blue lines in the gingival margin are deposits of lead sulfide that are made from lead dust by bacterial metabolism.

Other Organs

• A defect in vitamin D synthesis is seen in children with blood lead levels as low as 12 µg/dL
• Lead lines are also observed in roentgenograms as increased density by lead absorbance at the metaphyseal plate of growing long bones.

Molecular Perspective

• Lead exerts deleterious effects on intracellular biochemical pathways, alters protein and nucleic acid synthesis, ion transport, and metabolism.
• Decreased activity of ALA dehydratase is a sensitive indicator of lead toxicity.
• Lead displaces Zn from the enzyme, inactivating it.
• Lead exposure is a well-known cause of elevated levels of urinary coproporphyrin and red cell Zn-protoporphyrin, and these metabolites are often used to monitor occupational lead exposure.

Additional Lead Poisoning Effects and Mechanisms

• Increased erythrocyte protoporphyrin, resulting from industrial lead exposure was first described in 1946.
• Inhibition of ferrochelatase's activity by lead in vitro can elevate red cell protoporphyrin.
• Zn-protoporphyrin, rather than free protoporphyrin, accumulates in the red cells of lead-intoxicated individuals.
• Lead interferes with the utilization of iron, inhibits iron uptake from transferrin, and impairs mitochondrial function.
• Lead causes metabolic abnormalities, including acquired deficiency of pyrimidine-specific 5'-nucleotidase.
• Lead disrupts the plasma membrane of red blood cells by inhibiting (Na+, K+)ATPase activity.
• Kidneys are especially vulnerable to lead poisoning because they readily accumulate lead.

Lead Poisoning in Kidneys

• Exposure to lead in kidneys leads to the appearance of intracellular inclusion bodies and alterations in mitochondrial morphology.
• These include the most common lining cells of the proximal tubules.
• Low lead levels enhance the spontaneous or basal release of neurotransmitters from presynaptic nerve endings.
• Lead also inhibits evoked release of neurotransmitters in the central nervous system.
• Calmodulin has a higher affinity for lead than for calcium.
• Protein kinase C activators enhance long-term potentiation, while inhibitors block it.
• Lead can activate protein kinase C, causing its translocation from the cytosol to the membrane.
• Brain capillary endothelial cells are responsible for the blood brain-barrier formation.
• Astrocytes are particularly vulnerable to the toxic effects of lead.

Lead Poisoning Treatment

• If a large number of children in a community have blood lead levels ≥10 µg/dL, community-wide interventions should be considered to be appropriate agencies.
• Management of lead hazards should begin at a blood lead level of 15 µg/dL.
• Children with blood lead levels ≥20 µg/dL need to undergo a complete medical evaluation.
• Asymptomatic children with blood lead levels ≥45 µg/dL should receive chelation therapy with CaNa₂EDTA.
• Symptomatic children with blood lead levels ≥45 µg/dL or asymptomatic children with blood lead levels ≥70 µg/dL represent an acute medical emergency.
• Environmental assessment should be done for all work sites to measure the lead content of dust and fumes in workers.
• Adults with mild/moderate symptoms and blood lead levels of >50 µg/dL should be given CaNa₂-EDTA.
• With severe lead encephalopathy, BAL and CaNa₂EDTA should be administered to adults.
• Women aged under 45 years should be banned from lead-handling work.