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

XI. Toxicology
865
Succinyl Co-A+Glycine
ALA synthetase +
Pyridoxal - PO 4
-Amino Levulinic Acid (ALA)
ALA in urine
ALA - dehydratase
ALA-dehydratase
in blood
Porfobilinogeen (PBG)
Protoporphyrine IX
EP
ZPP
Heme - Synthetase
Fluorocytosis
+ Fe ++
Heme
FIGURE 28-19 Schematic representation of heme synthesis. Lead
interferes with the enzyme δ -aminolevulinic acid dehydratase (ALA-D),
resulting in a lower activity of ALA-D in blood and a higher concentration
of δ -aminolevulinic acid in the urine. Interference with the enzyme
heme synthetase leads to an accumulation of protoporphyrin IX in the
erythrocytes, which can be measured as FEPP or ZPP and leads to fluorocytosis.
Reprinted with permission from Lumeij (1985b) .
TABLE 28-4 Blood Protoporphyrin IX Concentrations
Measured on the Hematofluorometer and
Corresponding Clinical Signs of Pb Poisoning in
Mallard Ducks
Blood Protoporphyrin IX
Clinical Signs
801 μ g/dl
Death
( 14.4 μ mol/L) Inability to stand, walk, fly
Loss of voice
Green watery diarrhea
501–800 μ g/dl Muscular weakness
(9.0–14.4 μ mol/L) Easily fatigued
Unsteady gait
Slight tail drop
Green watery diarrhea
201–500 μ g/dl Hyperexcitability
(3.6–9.0 μ mol/L) Green watery diarrhea
40–200 μ g/dl Green watery diarrhea
(0.7–3.6 μ mol/L)
0–39 μ g/dl No evidence of Pb poisoning
0–0.7 μ mol/L
From Roscoe et al. (1979) .
light (400 nm), 75% to 100% of the erythrocytes show a red
fluorescence: fluorocytes. The accumulated protoporphyrin
imparts the red fluorescence to fluorocytes ( Beeson et al .,
1979 ). The fluorocyte test has also been used successfully
for the diagnosis of Pb poisoning in rabbits ( Roscoe et al .,
1975 ) and waterfowl ( Barret and Karstad, 1971 ).
In humans, FEPP binds to zinc to form the fluorescent
compound zinc protoporphyrin (ZPP), which can be
measured fluorometrically in a single drop of whole blood
(Roscoe et al ., 1979 ). Roscoe et al . (1979) found that blood
fluorescence spectra of Pb-poisoned mallards scanned on
a fluorescence spectrophotometer were characteristic of
metal-free protoporphyrin IX. They suggested that the reason
for chelation of zinc by FEPP in human erythrocytes and not
in duck erythrocytes might be due in part to the fact that duck
erythrocytes contained only about one-third as much zinc as
the human erythrocytes. By changing the factory-installed
emission filter in a commercially available fluorometer used
to screen humans for Pb intoxication by measurement of
ZPP, they made the instrument suitable to measure FEPP.
They found that FEPP concentrations were at their highest
8 days after Pb-shot ingestion in mallard ducks. The highest
value they recorded was 2284 μ g/dl. FEPP was rarely elevated
( 40 μ g/dl) in freshly drawn blood from Pb-poisoned
ducks. However, when the same blood was oxygenated and
refrigerated before testing, FEPP concentrations increased
because of in vitro synthesis, which terminated within 2 days.
No such increase was manifested by controls. They found
that FEPP concentrations were related to the clinical signs of
Pb poisoning in mallard ducks, and those with FEPP higher
than 500 μ g/dl began to show impaired motor function that
could seriously affect their survival ( Table 28-4 ).
In raptors, birds showing clinical signs of Pb toxicosis
had consistently higher ZPP levels than other Pb-dosed
birds with similar blood Pb values ( Reiser and Temple,
1981 ). False-positive FEPP and ZPP elevations occur in
humans with iron deficiency anemia or erythrocytic protoporphyria
( Wijngaarden and Smith, 1982 ).
B . Zinc
Zinc poisoning has been reported in birds after ingesting
(United States) pennies minted after 1983 (98% zinc) or
metal fence clips (96% zinc). Galvanized wire is another
well-known source of zinc poisoning in aviary birds (new
wire disease). Clinical signs include weight loss, depression,
anorexia, gastrointestinal signs, and posterior paresis.
Pathological lesions are especially seen in the pancreas and
include acinar atrophy and proliferation of pancreatic ductules
( Howard, 1992 ; Labonde 1995 ; Lloyd, 1992 ; Morris,
1985 ; Reece, 1986 ; Wight et al ., 1986 ; Zdziarski et al .,
1994 ).
Serum zinc concentrations can be used to establish a
diagnosis, but extreme care must be taken to exclude contamination
from zinc containing grommets from plastic
syringes or rubber stoppers from collecting tubes ( Minnick
et al ., 1982 ). Serum zinc concentrations in an affected group
of ducks were 1260 to 1660 μ g/dl. Values in a reference