Diagnosis

Lead toxicity

Etiology

Cause [4kt]

1. Inhalation: paint, gasoline, cutting, mining, welding, battery/glass manufacture

2. Ingestion: tap water due to atmosphere contamination, food

Pathophysiology [4kt]

1. Lead is not biodegradable and show remarkable environmental persistence [4kt]

2. Lead has no physiologic role in biological systems and disturbs multiple enzyme systems by mimicking calcium and zinc [aej]

3. Human organs and tissues have no effective mechanism to excrete lead, thus its concentration inside the body accumulates and increases with age [dpi]

4. Lead has a half-life of approximately 30 days in the blood, from where it diffuses into the soft tissues, including the kidneys, brain, liver, heart and bone marrow.

5. Half-life in bone is several decades and lead is primarily excreted in urine and bile

6. Children inhale more air relative to their body size and absorb 40-50% of the lead they ingest (adults 10-15%) [4kt]

7. Acute lead toxicity:

   • Nephropathy: proximal tubule dysfunction --> Fanconi-like syndrome

   • Abdominal pain

   • Neuropathy: lead undermine the normal synaptic pruning process

   • Encephalopathy

   • Anemia

8. Chronic lead toxicity: Accumulation in the intestines, lungs, liver, spleen, kidneys, central nervous system and bones and a possible contributing cause of the downfall of the Roman Empire: [dpi][at3]

   • Neurological Toxicity: irritability, lower IQ, ADHD-symptoms, delirium, convulsions, encephalopathy, headache, ataxia, somnolence, hallucinations

   • Lethargy, seizures, stupor, coma

   • Hematological Toxicity: interfering with enzymes in heme synthesis --> Anemia

   • Gastrointestinal Toxicity: colic, nausea, vomiting and anorexia

   • Renal Toxicity/hypertension/gout: nephropathy, phosphaturia, glucosuria and proteinuria

   • Cardiovascular Toxicity: stroke, rheumatic/valvular/ischemic/hypertensive heart disease, cardiomyopathy, myocarditis, endocarditis, atrial fibrillation/flutter, aortic aneurysm, peripheral artery disease, chronic kidney disease, diabetes mellitus types 1/2 [iau]

   • Reproductive Effects: reduction in libido, abnormal spermatogenesis, chromosomal damage, infertility, stillbirth, miscarriage

Complications [4kt]

• Encephalopathy

• Hypertension

• Cardiovascular morbidity

• Chronic or recurrent abdominal pain

Epidemiology

Prevalence per 100.000 [e7i][6qz][iau]

Approach

• Blood test: blood lead level when acute poisoning

• Blood smear

• Abdominal x-ray

• Long bones x-ray

• Ophtalmoscopy

• CT caput

• MR caput

• EEG

• Lumbar punture

• Free erythrocyte protoporphyrin level

• Provocative chelation test (CaNa2 EDTA)

Treatment

Chelators remove lead from blood and tissue (including the brain). Chelation therapy is recommended with a venous BLL ≥45 μg/dL, but should be used with caution. Intravenously administered chelating agents are the treatment of choice for severe lead toxicity: [4kt]

1. Dimercaprol (2,3-dimercapto-1-propanol or British Anti-Lewisite) 75 mg/m2 intramuscular injection every four hours for five days

2. CaNa2EDTA (calcium disodium ethylenediamine tetra-acetate) 1-1.5 g/m2/day as a continuous infusion for five days

3. DMSA, or succimer (meso-2,3-dimercaptosuccinic acid) orally 350 mg/m2 three times daily for five days, then twice daily for 14 days

Differential diagnoses

Anemia, Constipation, Depression, Encephalitis, Epilepsy, Fanconi syndrome, Gout, Guillain-Barre syndrome, Hypertension, Mercury toxicity, Polyneuropathy, Renal failure, Syndrome of inappropriate antidiuretic hormone secretion