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

444
Chapter | 14 Gastrointestinal Function
mannitol in the evaluation of intestinal permeability has
been reported in healthy cats ( Papasouliotis et al., 1993 ).
The cellobiose-to-mannitol urinary excretion ratio was
increased in Irish setters with gluten-sensitive enteropathy
( Hall and Batt, 1991a, 1991b ). Simultaneous quantification
of rhamnose, lactulose, 3-O-methyl-D-glucose, and xylose
in urine by a unique chromatographic technique has been
reported to assess both intestinal function and permeability
( Sorensen et al., 1993 ).
J . Protein-Losing Enteropathy
Albumin, IgG, and other plasma proteins are present in
low concentration in normal gastrointestinal secretions.
Because protein usually undergoes complete degradation
within the intestinal lumen, it has been suggested that the
gastrointestinal tract must have a physiological role in the
catabolism of plasma proteins. The relative significance of
this pathway, however, has been the subject of considerable
controversy. Some investigators have concluded, for example,
that as much as 50% or more of the normal catabolism
of albumin ( Campbell et al., 1961 ; Glenert et al., 1961,
1962 ; Wetterfors, 1964, 1965 ; Wetterfors et al., 1965 ) and
ϑ -globulin ( Andersen et al., 1963 ) may occur in the gastrointestinal
tract. Others believe that the physiological role
of the intestine in plasma protein catabolism is far less significant,
accounting for about 10% of the total catabolism
( Franks et al., 1963a, 1963b ; Katz et al., 1961 ; Waldmann
et al., 1967, 1969 ).
Regardless of questions concerning the physiological
significance of the gastrointestinal tract in plasma protein
catabolism, it is well established that normal intestinal
losses are substantially increased in a variety of gastrointestinal
diseases, collectively referred to as the proteinlosing
enteropathies (PLE). The increased loss causes
hypoproteinemia (especially hypoalbuminemia), which
may be observed in various types of chronic enteric diseases.
The excessive losses are the result of ulcerations or
other mucosal changes that alter permeability or obstruct
lymphatic drainage from the intestine. If severe, hypoalbuminemia
may result in retention of fluid with development
of ascites and subcutaneous edema of pendant areas.
Excessive plasma protein loss has been seen in swine
with chronic ileitis (Nielsen, 1966) , in calves with acute
enteric infections ( Marsh et al., 1969 ), in cattle with parasitic
or other inflammatory abomasal disease ( Halliday
et al., 1968 ; Murray, 1969; Nielsen and Nansen, 1967 ),
and in Johne’s disease ( Patterson et al., 1967 ; Patterson
and Berrett, 1969 ). In addition to the classic mucosal and
submucosal lesions of Johne’s disease, secondary intestinal
lymphangiectasia can occur. Meuten et al. (1978) observed
PLE associated with granulomatous enteritis in two horses.
PLE is seen with some frequency in the dog ( Campbell
et al., 1968 ; Farrow and Penny, 1969 ; Finco et al., 1973 ;
Hayden and Van Kruiningen, 1973 ; Hill, 1972; Hill and
Kelly, 1974 ; Mattheeuws et al., 1974 ; Milstein and
Sanford, 1977 ; Olson and Zimmer, 1978 ). The most common
cause appears to be lymphocytic-plasmacytic enteropathy.
Intestinal lymphangiectasia also has been reported
as a cause of increased intestinal protein loss; it is most
commonly seen in small terrier breeds (e.g., Yorkshire,
Maltese) and the Norwegian Lundehund, suggesting a
genetic predisposition ( Simpson, 2005 ). Increased plasma
protein loss from the stomach has been seen in dogs with
hypertrophic gastritis.
Familial protein-losing enteropathy (PLE) and proteinlosing
nephropathy (PLN) have been described in softcoated
wheaten terriers ( Littman et al., 2000 ). Dogs with
PLE were diagnosed earlier than dogs with PLN or with
both diseases. Clinical signs included vomiting, diarrhea,
weight loss, pleural and peritoneal effusions, and thromboembolic
disease. Panhypoproteinemia and hypocholesterolemia
were consistent findings and intestinal lesions
included inflammatory bowel disease, dilated lymphatics,
and lipogranulomatous lymphangitis. In another study,
food hypersensitivities were identified in six affected
dogs ( Vaden et al., 2000 ), but the presence of preexisting
inflammatory disease made it impossible to determine if
food allergies were the cause or result of enteric disease.
Increased intestinal protein loss is the most likely cause
of the hypoalbuminemia associated with certain other
enteric diseases including lymphoma and malabsorptive
syndromes. Munro (1974) demonstrated that protein loss
in dogs with experimentally induced protein-losing gastropathy
occurs by an intercellular route. Isotope-labeled
polyvinylpyrrolidone ( 131 I-PVP),
51
Cr-labeled ceruloplasmin,
and 51 Cr-labeled albumin have been used to evaluate
enteric protein loss in the dog ( Finco et al., 1973 ; Hill and
Kelly, 1974 ; Olson and Zimmer, 1978 ; van der Gagg et al.,
1976 ).
Fecal alpha 1-proteinase inhibitor ( α 1-PI) is minimally
degraded as it passes down the gastrointestinal tract. In
conditions where there is excessive loss of plasma protein
into the gut, there is an increase in fecal α 1-PI ( Williams
et al., 1990 ). The value of this test has been reported in
dogs with chronic gastrointestinal disease ( Murphy et al.,
2003 ; Ruaux et al., 2004 ) and in cats with inflammatory
bowel disease or gastrointestinal neoplasia ( Fetz et al.,
2006a, 2006b ).
Murphy et al. (2003) reported that fecal α 1-PI concentrations
in dogs with gastrointestinal diseases associated
with histological abnormalities (median 60.6 μ g/g, range
7.4–201.7 μ g/g) were higher than dogs with gastrointestinal
disease and normal histology (median 3.8, 0.7–74) and
control dogs (9.9, 0.0–32.1). Although there was no direct
correlation with serum albumin levels, the fecal α 1-PI was
believed to be a useful test in identifying early stages of
PLE before decreased levels of serum albumin occurred.
Moreover, the test was useful in justifying gastrointestinal
biopsies in some cases. Ruaux et al. (2004) reported that