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

VIII. Disturbances of Gastrointestinal Function
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system. These O 2
are metabolized to H 2 O 2 , and the latter
reacts with Cl to form hypochlorous acid. Myeloperoxidase
(MPO), an enzyme contained in neutrophils, catalyzes this
reaction. MPO activity in intestinal mucosa correlates well
with the degree of neutrophil infiltration and mucosal injury.
Serine proteases are believed to play a contributing role
in ischemia-reperfusion injury ( Moore et al., 1995 ). The
pancreas is an important source of endoproteases (trypsin,
chymotrypsin, and elastase), which can cause mucosal
injury, particularly in the small intestine. Proteases
produced by granulocytes, as well as lysosomes, are more
important in mucosal injury of the large bowel, elastase,
neutral proteases, and cathepsin G are released from granulocytes
during phagocytosis. Cathepsin B is a lysosomal
protease that has trypsin-like activity.
Several pharmacological agents have been used in experimental
and clinical studies of ischemia-reperfusion injury
(Moore et al., 1995 ). The mechanistic rationale for many
of these agents is comparable to the role of endogenous
antioxidants. Examples of commonly used agents include
xanthine oxidase inhibitors (allopurinol), deferoxamine,
21-aminosteroids, inhibitors of PLA2, cyclooxygenase, and
lipoxygenase. Superoxide dismutase (SOD), catalase, and
glutathione peroxidase (Gpx) are free radical scavenging
enzymes. Mannitol, albumin, dimethyl sulfoxide (DMSO),
dimethyl thiourea, and manganese chloride represent nonenzymatic
free radical scavengers. Other agents that have been
studied include nitric acid, protease inhibitors, hydroxyethyl
starch, and neutrophil-directed agents. Although there has
been demonstrable efficacy of the aforementioned agents in
some studies, there are many inconsistencies. From a clinical
perspective, success has been limited with single agents, and
there is more interest in combination or multimodal therapy.
D . Acute Diarrheas
The term diarrhea is used to generically describe the passage
of abnormally fluid feces with increased frequency,
increased volume, or both. The significance of diarrhea
depends primarily on the underlying cause and on the
secondary nutritional and metabolic disturbances that are
caused by excessive fecal losses.
There are theoretically three factors that can act independently
or in combination to produce diarrhea. An
increase in the rate of intestinal transit is one factor
believed important in functional disorders of the gastrointestinal
tract in which “ hypermotility ” has been considered
to be the primary cause. Although increased intestinal
motility may be a factor in certain types of diarrheal disease,
when motility patterns have been investigated, diarrheal
disease has actually been associated with decreased
motility ( Christensen et al., 1972 ). A second factor in the
pathogenesis of diarrhea is decreased intestinal assimilation
of nutrients that may result either from decreased intraluminal
hydrolysis of nutrients (e.g., maldigestion resulting
from pancreatic exocrine insufficiency), bile salt
deficiency, or defective mucosal transport of nutrients (i.e.,
malabsorption ) that results from various types of inflammatory
bowel disease, villus atrophy, intestinal lymphoma,
or intrinsic biochemical defects in the mucosal cell that
interfere with digestion or absorption. Finally, increased
intestinal secretion of water and electrolytes is a major factor
in the pathogenesis of certain types of acute diarrhea.
Enteropathogenic strains of Escherichia coli produce
soluble enterotoxins ( Kohler, 1968 ; Moon, 1978 ; Smith
and Halls, 1967 ), which alter bidirectional Na and water
flux ( Fig. 14-8 ). The most extensively studied enterotoxin
is that produced by Vibrio cholerae. This bacterium produces
a large-molecular-weight, heat-labile toxin (CT),
one subunit of which has properties similar to those of the
heat-labile (LT) enterotoxin produced by certain strains of
E. coli ( Richards and Douglas, 1978 ). The mechanism of
action of CT is believed to involve the activation of adenylate
cyclase. This membrane-bound enzyme converts
ATP to cAMP, which through the action of protein kinase
is responsible for the greatly increased secretion of water
and electrolytes by the intestinal mucosa. Although species
differences have been observed ( Forsyth et al., 1978 ), this
mechanism appears to be important in the mode of action
of LT of E. coli as well ( Richards and Douglas, 1978 ).
FIGURE 14-8 Pathogenesis of diarrhea caused by E. coli enterotoxin and by coronaviruses. From Moon (1978) .