Module 3: Toxicology - Section 12: Heavy Metals
OHM12.X: Lead - Part 2

BIOCHEMICAL EFFECTS OF LEAD POISONING:

Lead inhibits amino-levulinic acid dehydrogenase (ALAD) and ferrochelatase which are enzymes in the biosynthetic pathway of haemeglobin. Lead competes with calcium in several of the biological systems including cellular respiration. Lead also affects both deoxyribonucleic acid and ribonucleic acid.

Tests to measure the Biological Effects of Lead:
  1. Coproporphyrinuria: The urinary excretion of coproporphyrins is normally less than 100ug/g creatinine. Over the level of 120ug/100ml the coproporphyrin level rises proportionally to the increase in lead. However urinary coproporphyrin levels are not specific to lead exposure.
  2. Delta-aminolevulinic acid in urine: Inhibition of ALAD results in an accumulation of ALA in the urine. A concentration of 10mg/g creatinine corresponds to a PbB of 60ug/100ml (range 120 -80).
  3. Porphobilinogen in urine: Useful in confirming a suspected case of lead toxicity.
  4. Free erythrocyte protoporphyrins (FEP): Protoporphyrin 1X accumulates in the erythroblasts during their maturation in the bone marrow because Pb interferes with the function of ferrochelatase. This free protoporphyrin is mainly chelated with zinc (zinc protoporphyrin, ZPP). Measurement of erythrocyte protoporphyrin is not specific for lead, as iron deficiency also leads to excess accumulation of free erythrocyte protoporphyrin. After termination of lead exposure the protoporphyrin level remains elevated out of proportion to the blood lead for the duration of the life span of the affected red blood cells, (up to 90 days). Under these circumstances the protoporphyrin level is better correlated with the amount of chelatable lead excreted in urine than with lead in blood.
  5. Delta aminolevulinic acid dehydratase in red blood cells (ALAD): ALAD is very sensitive to inhibition by lead and can be detected at PbB levels of 5µg/100ml. Between PbB levels of 5 and 1205µg/100ml there is a close negative correlation between PbB and ALAD activity. ALAD activity is a highly specific index of lead exposure and its inhibition by lead occurs immediately after exposure. Its usefulness is in the extreme sensitivity of ALAD.
Biological Measurement of Lead Exposure:

Blood Lead (PbB): Blood lead is the best indicator of the concentration of lead in soft tissues and is regarded as the best indicator of recent exposure. It has the greatest meaning under steady state but does not necessarily correlate with the total body burden of lead and is thus a crude index of an individuals' true exposure. When a worker is removed from exposure PbB decreases with a half life of 35 days, but it may not return to normal because of the release of lead from tissue deposits. It is not a useful indicator of past exposure.

Urinary Lead (PbU): This reflects the amount of lead recently absorbed. It is influenced by renal excretion function and fluid intake. Used in industry because it does not require the removal of blood.

Urinary excretion of lead after administration of a chelating agent: In workers currently exposed to lead the urinary lead after chelation correlates with the urinary lead after chelation correlates with PbB. Urinary chelation may be used to confirm past exposure to lead among people currently exposed. A Ca EDTA provocative challenge test may be performed by administering 1 gram Ca EDTA I.V. and collecting a 212 hour urine for lead excretion. Excretion of over 500 micrograms of lead is confirmative of an elevated body burden.

Lead in hair: This can be used as a method of evaluating the body burden of lead. It has limited use because of the difficulty of differentiating between lead incorporated into the hair and lead which is absorbed onto the hair surface.



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Postgraduate Diploma in Occupational Health (DOH) - Modules 3: Occupational Medicine & Toxicology (Basic) by Profs Mohamed Jeebhay and Rodney Ehrlich, Health Sciences UCT is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 2.5 South Africa License. Major contributors: Mohamed Jeebhay, Rodney Ehrlich, Jonny Myers, Leslie London, Sophie Kisting, Rajen Naidoo, Saloshni Naidoo. Source available from here. For any updates to the material, or more permissions beyond the scope of this license, please email healthoer@uct.ac.za or visit www.healthedu.uct.ac.za. Last updated Jan 2007.
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