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Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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256<br />

Chapter | 8 Porphyrins and the Porphyrias<br />

for lead exposure. Erythrocyte ALA-D is strongly inhibited<br />

by lead, and as a result, ALA rises in plasma and is<br />

excreted in the urine. Measurement <strong>of</strong> ALA is difficult,<br />

and the results lack sensitivity for low-level lead exposure;<br />

therefore, instead <strong>of</strong> its substrate ALA, erythrocyte ALA-D<br />

is more commonly assayed. Farant and Wigfield (1982) ,<br />

using the ratio <strong>of</strong> ALA-D activities assayed at two different<br />

pH’s, demonstrated ALA-D inhibition at blood lead<br />

concentrations <strong>of</strong> 10 to 15 μ g/dl (0.50 to 0.70 μ mol/l). They<br />

found this to be a highly sensitive and reliable index <strong>of</strong> the<br />

blood lead concentration.<br />

Coproporphyrin also rises in plasma and is excreted<br />

in urine, and like ALA, it is also difficult to measure and<br />

lacks sensitivity. Hence, this method is not used as an<br />

index <strong>of</strong> lead poisoning.<br />

FER-Ch is the second major enzyme that is strongly<br />

inhibited by lead, and as a result, PROTO IX accumulates<br />

in the erythrocytes. This PROTO IX is a zinc complexed<br />

PROTO IX instead <strong>of</strong> the “ free ” PROTO IX. Piomelli et al .<br />

(1982) found that erythrocyte zinc PROTO IX increased<br />

when blood lead concentrations were at 15 to 18 μ g/dl<br />

(0.75 to 0.85 μ mol/l).<br />

It is not quite as sensitive an index <strong>of</strong> blood lead concentration<br />

as ALA-D but is well below the diagnostic criteria<br />

for lead poisoning. George and Duncan (1981) found<br />

marked elevations in erythrocyte PROTO IX in experimental<br />

lead poisoning in calves. Modern fluorometers<br />

specifically designed to measure porphyrins have greatly<br />

simplified the assay. For these reasons, the current test <strong>of</strong><br />

choice to monitor lead exposure is the blood zinc PROTO<br />

IX concentration.<br />

The final diagnosis <strong>of</strong> lead poisoning ultimately rests<br />

on the measurement <strong>of</strong> blood lead concentration, and this<br />

is best done using flame atomic absorption spectrophotometry.<br />

In children, a blood lead concentration <strong>of</strong> 30 μ g/dl<br />

(1.45 μ mol/l) is currently regarded as normal, but it has been<br />

shown that zinc PROTO IX rises at blood lead levels <strong>of</strong> half<br />

that amount ( Piomelli et al. , 1982 ). It is clear that the heme<br />

synthetic pathway is affected at blood lead concentrations<br />

well below that considered normal. Zook et al . (1970)<br />

reported a normal range for blood lead in the dog <strong>of</strong> 10 to<br />

50 μ g/dl (0.48 to 2.41 μ mol/l) and considered a blood lead<br />

concentration <strong>of</strong> 60 μ g/dl (2.90 μ mol/l) diagnostic <strong>of</strong> lead<br />

poisoning. In the domestic rabbit, the blood lead concentration<br />

is reported to be 2 to 27 μ g/dl (0.10 to 1.30 μ mol/l)<br />

( Gerken and Swartout, 1986 ). Therefore, lead concentrations<br />

<strong>of</strong> 30 μ g/dl (1.45 μ mol/l) are considered diagnostic<br />

<strong>of</strong> lead poisoning in the dog and in all animals.<br />

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