Lead toxicity

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Lead compounds were used in paint in households in at least the 19th century in the UK, and may be exposed by sanding and other decorating or construction work. Children have absorbed sufficient lead from such surfaces to be poisoned. Another such source is face painting. Cases have also been described due to lead in colourful glasses in mugs[1]. Elemental lead should not be confused with 'lead' in pencils which is made from carbon (graphite).

Tetra-ethyl lead, a neurotoxin, was an early additive to petrol, reducing pre-ignition. This was widely abandoned in the latter years of the 20th century but still may cause exposure in some third world countries or from aviation sources[2]. A significant amount of lead itself entered the environment around roads from this source.

Late in 2015 it was discovered that a 2014 change in water supply in Flint, Michigan poisoned around 100,000 people. This is a potential problem anywhere where lead might have been used as a component in the metal in water supply pipes historically[3].

QuotationMarkLeft.png The psychometric and behavioral assessments of lead-exposed children who were randomized to outpatient chelation or placebo therapy in the TLC study revealed no benefit of therapy at age 7 years. Unlike our first wave of follow-up, for which assessments were conducted over a relatively broad age range (48–70 months), the testing reported here was conducted in a more carefully controlled age window and after children had entered school. Testing at age 7 allows assessment of cognitive and performance skills that are absent or inaccessible in the preschool-aged child. The absence of benefit at this later age adds credence to the earlier negative findings13 and reiterates the failure of chelation therapy to alter cognitive and behavioral outcomes in preschool children with blood lead levels in the range of 20 to 44 µg/dL. QuotationMarkRight.pngchildren with lead poisoning

Contents

Clinical presentation

  • Acute
    • Abdominal pain due to lead colic, constipation, colonic pseudo-obstruction
    • Dysgeusia
    • Fatigue
    • Arthralgia
    • Cognitive changes
  • Subacute/Chronic
    • As above but may be more vague
    • Lead lines (bluish pigmentation at the gum–tooth line) in sub acute poisoning
    • Hypertension1
    • Neuropsychiatric effects
    • Syndrome of inappropriate secretion of antidiuretic hormone (SIADH)
    • Microcytic anaemia (with normal total iron binding capacity, basophilic stippling on blood film and a haemolytic component (raised reticulocytes)
    • Hypophosphataemia(which may be due to renal phosphate wasting)

Pathophysiology

Haeme synthesis is impaired when 5-aminolevulinic acid dehydratase is 80 to 90% inhibited which occurs at a blood lead level of approximately 5.5 μg/mL. Features are similar to those of patients with acute porphyria, indeed plumboporphyria, due to a deficiency of ALA dehydratase is named by this analogy (plumbum:Latin:lead). Lead inhibits other enzymes active in the haeme biosynthetic pathway, including coproporphyrinogen oxidase, and ferrochelatase. This leads to more incorporation of zinc instead of iron into protoporphyrin IX (the immediate precursor of haeme). Lead inhibits erythrocyte pyrimidine 5'-nucleotidase and this results in a chronic haemolytic anaemia.

Measurement

Blood lead level, in an EDTA venous sample, is probably best. A level of 1 μg/mL or higher is considered elevated in adults. Levels of over 100 μg/dL (10 µg/mL) may be seen in acute lead poisoning. Zinc protoporphyrin (ZPP) has also been measured but may be less reliable although it has been suggested to correlate to total lead burden. Free erythrocyte protoporphyrin and zinc protoporphyrin correlate best with 3 month exposure to lead. There is no elevation of porphobilinogen level in lead poisoning unlike in porphyria. Lead is stored in the bones (this can be seen on X-ray imaging), but this can also cause prolonged toxicity, even after removal of the source of exposure.

Treatment

With severe symptoms chelation treatment:

  • Calcium disodium EDTA
  • 2,3-dimercaptosuccinic acid (succimer)

References