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

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Chapter | 27 Clinical Biochemistry in Toxicology
toxicant, nitrite. Monogastrics and ruminants are equally
susceptible to nitrite-based fertilizers ( Osweiler et al. ,
1985 ). Nitrate/nitrite intoxication produces a brown discoloration
of the blood caused by methemoglobinemia.
Carbon monoxide (CO) competes with oxygen binding
to the heme moiety in hemoglobin and myoglobin. CO
affinity for the hemoglobin binding site is approximately
200 times that of O 2 , resulting in tightly bound carboxyhemoglobin
and decreased blood oxygen transport. Because
continuous delivery of O 2 is critical to the heart and brain,
carbon monoxide may induce signs of cardiotoxicity or
neurotoxicity. Anoxia of the liver, kidney, and muscle may
elevate serum enzymes referable to these systems.
Acetaminophen, propylene glycol, and zinc intoxication
in small animals and copper intoxication in ruminants have
been associated with Heinz body anemia ( Thrall, 2004 ).
CO, cyanide, and H 2 S are potent inhibitors of cytochrome
oxidase and may produce sudden death because of a failure
of oxidative metabolism, which precedes alterations in
clinical biochemistry or morphology.
Numerous plants contain cyanogenic glycosides that
may affect herbivores, especially ruminants. The most common
cultivated species include Cynodon spp., Sorghum spp.,
and Prunus spp. ( Jubb and Huxtable, 1993 ).
IX . TOXINS AFFECTING THE ENDOCRINE
SYSTEM
Carbadox/Mecadox is an antibacterial agent that, with
prolonged exposure at levels greater than 25 ppm, induces
degeneration of the zona glomerulosa of the adrenal gland
associated with reduced plasma aldosterone, hyperkalemia,
and hyponatremia ( Capen, 1993 ).
The drug ortho,-para2,2-bis(2-chlorophenyl-4-
chlorophenyl)- 1,1-dichloroethane (o,p’DDD) is toxic to the
zonae fasciculata and reticularis of the adrenal gland and is
used as therapy for canine hyperadrenocorticism. This toxin
reduces circulating cortisol levels.
Goitrogenic substances induce iodine deficiency
or inhibit organification of iodine (Kaneko, 1997b) .
Thiocyanates, produced by ruminal digestion of cyanogenic
glycosides from the toxic plants Cynodon spp. and
Trifolium repens , and goitrin, derived from Brassica spp.,
are goitrogenic. Mimosine (discussed later under integumentary
toxins) is metabolized in the rumen to a compound
that inhibits organic binding of iodine by the thyroid gland.
Thioamides (sulfonamides) inhibit thyroperoxidase. All of
these substances may reduce serum T 4 and T 3 . Iodine toxicity
producing hyperplastic goiter in horses has been associated
with feeding kelp.
Hepatic glucuronidation is the rate-limiting step for biliary
excretion of T 4 . Sulfation by phenol sulfotransferase
is the rate-limiting step for excretion of T 3 . Induction of
hepatic microsomal enzymes may increase T 4 /T 3 elimination
and disrupt the hypothalamic-pituitary-thyroid axis resulting
in excessive thyroid stimulating hormone (TSH).
Xenobiotics that induce hepatic microsomal enzymes
include benzodiazepines, calcium channel blockers, chlorinated
hydrocarbons, phenobarbital, PCBs, PBBs, retinoids,
and steroids ( Capen, 1993 ).
Toxins inducing hypercalcemia are discussed in
Section II . Certain species of the Solanaceous produce toxins
that may induce chronic atrophy of parathyroid chief
cells. Chronic nephrotoxicity, especially in the dog, may
result in hypocalcemia and hyperphosphatemia, which
stimulates excessive production of parathyroid hormone.
Impaired intestinal absorption of calcium and increased
mobilization from the skeleton also may occur secondary
to insufficient renal production of 1,25-dihydroxycholecalciferol
by the kidney ( Capen, 1993 ).
Vicia villosa (hairy vetch) produces angiocentric eosinophilic
granulomatous inflammation of the skin, myocardium,
kidney, lymph nodes, thyroid, and adrenal glands.
The mechanism is unknown. Biochemical alterations
suggest cardiotoxicity, nephrotoxicity, and depression of
serum thyroxine and cortisol levels may occur.
Ingestion of Xylitol, a sugar substitute used in cooking
and in sugar-free chewing gum, can cause a severe hypoglycemia
in dogs by inducing an exaggerated elevation of
plasma insulin levels ( Dunayer, 2004 ).
X . TOXINS AFFECTING THE NERVOUS
SYSTEM
Many acute and chronic neurotoxins ( Table 27-8 ) produce
illness or death without alterations detectable by routine
clinical biochemistry performed on blood or serum. The
cerebrospinal fluid (CSF) is usually normal in neurotoxicity;
however, mild elevations in protein and leukocyte
count may occur with lead poisoning ( Bailey and Vernau,
1997 ). Also, CSF sodium levels may be compared to serum
sodium levels to assist in the diagnosis of sodium toxicosis.
Sodium levels in serum may decline if the animal
acquires access to water or is administered IV fluids, but
the CSF sodium levels may remain elevated ( Niles, 2003 ) .
Elevation of myelin basic protein has been reported in CSF
in experimental fumonisin-induced leukoencephalomalacia
in ponies ( Brownie and Cullen, 1987 ).
Accumulations of endogenous toxins secondary to
hepatotoxicity and nephrotoxicity may produce neurological
dysfunction. Conversely, alterations that mimic hepatotoxicity,
nephrotoxicity, muscle toxicity, respiratory, and
gastrointestinal toxicity may occur secondary to ischemia/
anoxia from depression of cardiopulmonary centers or by
affecting sympathetic/parasympathetic balance.
Increased urinary excretion of delta-aminolevulinic
acid is a potential indicator of lead intoxication. Organophosphates
induce cholinesterase inhibition, which can be