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

VII. Toxins Affecting Erythrocytes and the Hematopoietic System
829
Angiotensin converting enzyme (ACE) is concentrated
on the luminal surface of pulmonary endothelial cells. Most
circulating ACE originates from the lung; however, many
tissues including tubular epithelial and endocrine cells
contain this enzyme ( Erdos, 1987 ). Serum ACE activity is
altered in chronic and acute pulmonary disease ( Hollinger,
1983 ). Unfortunately, assay for this enzyme is not readily
available in most veterinary clinical biochemistry laboratories,
and ACE remains primarily a research tool.
Acute pulmonary edema is the typical lesion resulting
from toxins affecting the epithelial-endothelial interface of
the alveolus. Because CO 2 is approximately 20 times more
diffusible than O 2 , early pulmonary edema typically results
in decreased P a O 2 , whereas P a CO 2 remains normal or may
decrease with hyperventilation producing respiratory alkalosis.
Severe pulmonary edema may result in elevated P a CO 2
(hypercapnia and respiratory acidosis) ( Carlson, 1997 ).
Chronic insult to the alveolar epithelial-endothelial interface
may progress to pulmonary fibrosis (e.g., paraquat
intoxication) and be associated with low PaO 2 and elevated
PaCO 2 . Pulmonary fibrosis impinging on the pulmonary vasculature
may induce pulmonary hypertension and cor pulmonale
associated with enzymological alterations suggestive
of hepatoxicity resulting from passive hepatic congestion.
Cattle are susceptible to several toxins that induce
acute pulmonary edema including ingestion of perilla
ketone in Perilla frutescens , 4-ipomeanol in sweet potatoes
( Ipomoea batatas ) infected with Fusarium solani ( Doster
et al. , 1978 ), and the generation of 3-methyindole by ruminal
Lactobacillus skatoli from tryptophan in lush pasture
grasses ( Breeze and Carlson, 1982 ).
Some of the pyrrolizidine alkaloids, notably monocrotaline
from Crotolaria spectabilis , may induce chronic
pulmonary arteriopathy resulting in pulmonary hypertension
that progresses to right heart failure and elevation of
enzymes suggestive of cardiotoxicity or hepatotoxicity.
Similar pulmonary arteriopathy occurs in pigs with chronic
fumonisin intoxication ( Casteel et al. , 1994 ).
Organochlorines and organobromines include chlorinated
naphthalenes, polychlorinated biphenyls (PCBs),
polybrominated biphenyls (PBBs), and dibenzofurans.
These industrial toxins are cumulative and result in hypovitaminosis
A that is associated with squamous metaplasia
of columnar epithelium of the respiratory tract and hyperkeratosis
as discussed under integumentary toxins.
The numerous chemotherapeutic agents that have been
associated with pulmonary toxicity or hypersensitivity
have been reviewed elsewhere ( Myers, 1993 ).
VI . TOXINS AFFECTING THE
GASTROINTESTINAL TRACT
Disease affecting the gastrointestinal tract is often clinically
apparent on the basis of vomiting or diarrhea. In
veterinary medicine, these are more often the result of
infectious disease rather than intoxication. However, the
possibility of gastrointestinal toxins ( Table 27-5 ) should be
considered, especially in acute outbreaks affecting several
animals sharing the same environment.
Vomiting and diarrhea may produce dehydration that
results in mild to moderate elevations of BUN, plasma protein,
packed cell volume (PCV), and urine specific gravity.
Metabolic alkalosis (increased pH, normal or increased
PCO 2 , increased HCO 3 and HCO 3 /H 2 CO 3 ) and hypochloridemia
may result from chloride loss associated with
vomiting ( Tennant and Hornbuckle, 1997 ) .
Metabolic acidosis (decreased pH, normal or decreased
PCO 2 , decreased HCO 3 and HCO 3 /H 2 CO 3 ) may result
from secretory loss of bicarbonate in diarrhea.
In the absence of evidence of malnutrition or hepatic or
renal disease, chronic gastrointestinal malabsorption or protein
loss should be considered as a potential cause of hypoproteinemia
(Kaneko, 1997a) .
Ingestion of strong acids or alkalis may induce immediate
and severe damage to the gastrointestinal mucosa.
The seleniferous plants, which may be associated with
acute gastroenteritis in herbivores, are discussed under the
integumentary system.
Trichothecenes, especially T-2, produced by Fusarium
spp. and the macrocyclic trichothecene produced by
Stachybotrys alternans are highly irritant and produce
acute ulceration and hemorrhage of the gastrointestinal
tract. These mycotoxins also produce acute ulcerative and
necrotizing lesions of the skin and chronic pancytopenia
with hemorrhage.
The estrogenic mycotoxin, zearalenone, may induce
rectal prolapse in pigs in addition to affecting reproductive
performance.
VII . TOXINS AFFECTING ERYTHROCYTES
AND THE HEMATOPOIETIC SYSTEM
Toxins inducing hemolysis ( Table 27-6 ) may produce elevations
of serum LDH, anemia, icterus, hemoglobinemia,
hemoglobinuria with secondary nephrotoxicity, and unconjugated
bilirubinemia.
Chronic, drug-induced, immune-mediated hemolysis
has been associated with para-aminosalicylic acid, chlorpromazine,
dipyrine, insecticides, penicillin, phenacetin,
quinine, quinidine, and sulfonamides ( Valli, 1993 ).
Mellitin is a hemolyzing component of Hymenopterous
toxins and comprises approximately 50% of bee venom
( Cheville, 1988 ). One report also attributes a case of
immune-mediated hemolytic anemia in a young dog to
exposure to bee venom ( Noble and Armstrong, 1999 ).
Chronic nephrotoxicosis leading to uremia may
decrease erythrocyte life span because products normally
eliminated by the kidney are retained. This mechanism