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

Chapter 27
Clinical Biochemistry in Toxicology
Kurt V. Kreutzer
Department of Biomedical Sciences
College of Veterinary Medicine
University of Missouri
Columbia, Missouri
James R. Turk
Department of Biomedical Sciences
College of Veterinary Medicine
University of Missouri
Columbia, Missouri
Stan W. Casteel
Medical Diagnostic Laboratory
College of Veterinary Medicine
University of Missouri
Columbia, Missouri
I. INTRODUCTION
II. HEPATOTOXICITY
III. NEPHRO TOXICITY
IV. TOXINS AFFECTING SKELETAL AND CARDIAC
MUSCLE
V. TOXINS AFFECTING THE LUNG AND RESPIRATORY
TRACT
VI. TOXINS AFFECTING THE GASTROINTESTINAL
TRACT
VII. TOXINS AFFECTING ERYTHROCYTES AND THE
HEMATOPOIETIC SYSTEM
VIII. TOXINS AFFECTING HEMOGLOBIN AND OXIDATIVE
METABOLISM
IX. TOXINS AFFECTING THE ENDOCRINE SYSTEM
X. TOXINS AFFECTING THE NERVOUS SYSTEM
XI. TOXINS AFFECTING THE INTEGUMENT
REFERENCES
I . INTRODUCTION
The availability of accurate historical information including
a list of the animal species affected, clinical signs, toxins
suspected, potential route of exposure, vehicle, relative
amount, and timing of exposure is often a limiting factor in
the diagnosis of toxic disease. This information permits the
diagnostician to make a rational selection of samples and
tests to be performed by considering the known target organs
of the toxins suspected. Unfortunately, this information is
often unavailable during the initial stages of an intoxication.
In the absence of such detailed history, the identification of
target organs using clinical biochemistry may help clinicians
to create a list of potential toxins retrospectively.
There are species differences in the most useful biochemical
markers of organ-specific cellular injury and in the susceptibility
to various toxins ( Kramer and Hoffmann, 1997 ). For
this reason, the following discussion is organized on an organ
system and species basis. Neither bacterial toxins nor hereditary
disease predisposing to intoxication will be discussed.
II . HEPATOTOXICITY
Many toxins induce hepatic injury (Table 27-1 ). The susceptibility
of the liver to toxic insult is in part a consequence
of its location between the digestive tract and the rest of the
body and the central role it plays in biotransformation and
disposition of xenobiotics ( Miyai, 1991 ; Snyder, 1979 ).
Extrahepatic metabolism of toxins by mixed function oxidases
may affect the target organ and potential hepatotoxicity
of a given xenobiotic ( Gram et al. , 1986 ). A variety
of factors including the induction of these enzyme systems
by drugs ( Snyder, 1979 ) and suppression of enzyme activity
by infectious agents and cytokines ( Monshouwer et al. ,
1995 ) may modify the response to a given toxin. Lipophilic
compounds tend to be more hepatotoxic than hydrophilic
ones because the latter are eliminated by the kidney ( Kelly,
1993 ). Many toxins are hepatotoxic and nephrotoxic, however,
and most toxins have multiple target organs.
The cytosolic enzyme alanine aminotransferase (ALT)
is found in both hepatocytes and skeletal muscle of animals.
The dog and cat have high levels of ALT in hepatocytes,
making it a useful marker for hepatocellular
injury in these species ( Stockham and Scott, 2002 ). The
plasma half-life of this enzyme in the dog is estimated to
be approximately 60 h. Increased serum levels parallel the
magnitude of hepatocellular injury in acute disease. Several
days following injury, ALT levels may be spuriously low.
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