Discussion
Our results indicated that many equids with gastrointestinal
disease/colic have increased serum pancreatic (DGGR) lipase
concentrations. The results showed a significantly higher median lipase
activity in horses with colic than those with colitis or peritonitis,
suggesting that a degree of pancreatitis may be present in many colic
cases, although this does not indicate causation, and, in many cases,
this is likely to be a secondary response, as is noted in people and
other species (Watson et al 2010; Watson 2015). An increased risk
of pancreatitis, as determined by increased serum pancreatic lipase
concentrations, has previously been reported in colic (Johnson et
al 2019; Lanz et al 2022). However, increased pancreatic lipase
activity has also been reported in animals, including horses, with a
variety of other non-gastrointestinal disease. For example, in the study
of Johnson et al (2019), hyperlipaseamia was identified in 16
horses affected by various conditions, including poor athletic
performance, lameness, anaemia, rhabdomyolysis, laminitis, cellulitis,
juvenile osteoarthritis and training. However, in the current study,
DGGR lipase concentrations were significantly higher in colic cases
compared to colitis and peritonitis cases, providing further evidence to
suggest a possible association between colic and pancreatitis. In
addition to this apparent association with colic, there were significant
associations between pain severity and lipase values in this study, with
higher lipase activities in horses with more severe pain. However there
was no significant association with heart rate. Although heart rate is
to some extent dependent on the level of pain and sympathetic response,
the rate is also significantly affected by other factors including
vascular volume and cardiovascular status (including hypovolaemia and
systemic inflammatory syndrome), which may explain why there was an
observed association with pain but not with heart rate. We also found no
association between pancreatic lipase activities and breed in this
study; this differs from the results of Johnson et al (2019) who
found that hot-blooded horses were more frequently affected.
Johnson et al (2019), reported increased DGGR-lipase activity
above the upper reference limit of 20 U/L in 40% of 109 hospitalised
horses; 33 of these horses had gastrointestinal disease, of which 28
(85%) had increased pancreatic lipase activity. This compares with
39.5% of equids with gastrointestinal disease that had hyperlipaseaemia
in the current study. Lanz et al (2022) measured serum
DGGR-lipase activity in a larger number (192) of horses with colic;
increased DGGR-lipase activity was demonstrated in 30.2% of horses with
signs of colic and was above twice the upper reference limit in 15.6%.
These results more closely align with the results of our study, where
pancreatic lipase concentration > 2xURL was identified in
13.2% of equids with gastrointestinal disease. The marked differences
in the prevalence of hyperlipaseaemia in the study of Johnson et
al (2020) with that of Lanz et al (2022) and our own study could
represent differences in the populations assessed; in the Johnsonet al (2019) study there were larger numbers of foals (up to a
year) and Thoroughbreds in training. Compared with horses with normal
pancreatic lipase concentrations, horses with colic with
hyperlipaseaemia in the study of Lanz et al (2022) had higher
percentages of non-survivors, surgical cases, strangulating diseases,
and large bowel displacements or torsion. In the current study we were
unable to demonstrate a statistically significant association between
pancreatic lipase concentration and outcome or any specific type of
disease, apart from identifying significant differences between medical
colic and colitis cases, surgical colic and colitis cases, and surgical
colic and peritonitis cases. This could also be reflective of a
difference in the population of animals studied. In our study, we also
found a significant difference in outcome (survival, euthanasia, died)
and lipase concentrations < or > 2xURL. One other
study (Bartel et al 2023) reported an elevation of pancreatic
lipase concentration in one horse with colic (out of a total of 19
horses tested). It is noteworthy that the prevalence of increased DGGR
lipase concentrations in horses with signs of colic in all of these
studies was higher than the prevalence of primary pancreatitis reported
in necropsy studies (Yamout et al 2012; Newman, 2015). This
finding suggests that hyperlipaseaemia, as diagnosed by increased DGGR
lipase activity, probably results from secondary pancreatic damage in
many cases (Lanz et al 2022).
Assessing the relevance of increased pancreatic lipase concentrations in
this and other studies is hampered by the lack of histopathological
examination of the pancreas; this was not feasible in the current study.
The prevalence of pancreatitis, based on the presence of
hyperlipaseaemia in this and other studies, is much higher than that
identified previously, before the DGGR lipase assay was available. For
example, the presence of pancreatitis, based on gross post-mortem and
histological examination, was diagnosed in only 4/834 (0.4%) horses
necropsied over nine years in one study (Newman 2015), and was diagnosed
via necropsy in only 43 cases in a 25-year period at another large
teaching hospital (Yamout et al 2012). In agreement with the
current and more recent studies where pancreatitis was diagnosed using
serum DGGR-lipase activity (Johnson et al 2019; Lanz et al 2020), the study by Yamout et al (2012) showed that pancreatitis
occurred frequently in association with gastrointestinal disease,
including large bowel torsion, colonic displacements, colonic impaction,
enteritis, small intestinal strangulation, etc. Pancreatitis associated
with the latter diseases has been reported previously. We also diagnosed
pancreatitis in a horse with entrapment of jejunum in the epiploic
foramen and it seems likely that trauma to the pancreas might be the
cause in such cases, since the pancreas borders the epiploic foramen; an
association with this disease has been recorded previously (Johnsonet al 2019). Displacement and torsion of the large colon has also
been associated with pancreatitis in several previous studies, possibly
due to disruption of the blood supply to the pancreas (Yamout et
al 2012) or shock-related hypoperfusion and mechanical compression
(Grulke et al 2003).
In dogs, increased pancreatic lipase activity may be also observed in a
variety of other non- pancreatic diseases, including portal
hypertension, gastrointestinal, renal, and endocrine disorders (Ralliset al 1996; Prümmer et al 2020; Serrano et al 2021); in the present study, increased DGGR-lipase concentration was
identified secondary to several other conditions, including non-specific
colic, enteritis, grain overload and post-foaling colic. Acute
pancreatitis has previously been reported in a donkey with grain
overload (Kawaguchi et al 2004).
Spontaneous gastric reflux in association with severely elevated DGGR
lipase activity was identified in 3 horses is this study, and gastric
reflux on passage of a nasogastric tube was present in a further 8
horses with severe hyperlipaseaemia; in total 11 of 15 (73%) horses
with severely raised pancreatic lipase concentration had gastric reflux.
This association has been recorded previously (Buote 2003; Kawaguchi et
2004; Waitt et al 2006; Bakos et al 2008; Yamout et
al 2012; Newman 2015; Lohmann and Allen 2015). The presence of gastric
reflux in a horse showing signs of acute colic should, therefore, raise
suspicion of pancreatitis if no other reason for the gastric reflux
(such as small intestinal obstruction) can be identified. Likewise, the
identification of distended loops of small intestine or thickened small
intestinal walls of FLASH scanning could indicate possible pancreatitis
if no other cause of these findings can be recognised. Distended loops
of small intestine have been identified either on rectal palpation or
ultrasonographically in cases of acute pancreatitis previously (Buote
2003; Kawaguchi et al 2004; Bakos et al 2008; Schmidtet al 2010; Yamout et al 2012; Newman 2015; Edery et
al 2015; Gomez et al 2015), however this finding is commonly
seen in horses with primary diseases causing small intestinal
obstruction (Beccati et al 2011).
We were unable to visualise the pancreas on abdominal ultrasonography.
Ultrasonographic identification of pancreatic damage, including a mass
effect between the liver and right dorsal colon has been previously
described in a 24-year-old Warmblood gelding with recurrent colic (Lacket al 2021). However, detailed ultrasonographic examination of
this area is not a specific aim of the FLASH procedure which was
undertaken in animals in this study.
In most animals which had elevated serum pancreatic lipase
concentrations at admission, and where sequential assays were
undertaken, the DDGR lipase concentrations reduced as the clinical
condition improved. This has been reported previously in two horses with
right dorsal displacement of the colon (Johnson et al 2019).
However, in the latter study, one of the horses showed a recurrence of
pain and a subsequent elevation of plasma DGGR lipase concentration 8
days after the initial episode of colic, suggesting that some horses may
be prone to recurrent episodes of pancreatitis, although this might
reflect recurrence of the gastrointestinal disease rather than
recurrence of primary pancreatitis.
There are several limitations of this study. We were unable to confirm
the presence of pancreatitis in any of the horses with elevated serum
DGGR lipase concentrations by post-mortem examination or histopathology.
This histopathological confirmation has not been reported in any other
studies, and requires further investigation. Traditionally,
histopathology has been considered to be the gold standard for the
diagnosis of pancreatitis and for distinguishing acute pancreatitis from
chronic pancreatitis (Cridge et al 2021). However, the
histopathological appearance does not always reflect the clinical
presentation of affected patients, and reliance on a histopathologic
diagnosis for acute pancreatitis is considered to be questionable
because lesions can be highly localised and the immediate clinical
relevance of lesions is unclear (Mansfield et al 2012). The work
of Johnson et al (2019) indicates that DGGR lipase is highly
specific for the equine pancreas, and it is widely used as a marker of
pancreatitis in other species (O’Brien et al 2014; Cridgeet al 2021). In addition, similar to previous reports of the use
of DGGR lipase in equids (Johnson et al 2019; Lanz et al 2020), the sample size for this study was small. Future studies
incorporating larger numbers and correlation with specific diagnostic
imaging and post-mortem/histopathological findings are warranted. The
results of this study should be appraised with reference to the
population of animals examined. In this study, all of the animals were
privately owned, and most commonly used for pleasure, so the results
cannot necessarily be extrapolated to other patient groups such as
competition horses and racehorses. A key disadvantage of convenience
sampling that was used in this study is that the sample lacks clear
generalizability. We were reliant on the availability of surplus blood
samples, and there was a likely bias towards sampling surgical colics,
colitis cases and peritonitis cases because these cases would be more
likely to have surplus blood samples available.
In conclusion, the results of this study indicate that pancreatitis, as
evidenced by increased serum DGGR lipase concentrations, is frequently
present in horses presenting with signs of colic. In many cases this
seems likely to represent a secondary pancreatitis. This observation
appears to be more common in certain diseases including colon torsion,
colonic displacements, enteritis, entrapment of the small intestine in
the epiploic foramen, etc. In addition, horses with colic presenting
with gastric reflux (including spontaneous reflux) and horses with
ultrasonographic evidence of distended/thickened loops of small
intestine may be more likely to have elevated DGGR lipase
concentrations. In most cases, the DGGR lipase concentration reduces
once the underlying disease resolves. However, in some cases, it is
possible that primary acute pancreatitis may cause colic signs, although
distinguishing these from secondary pancreatitis associated with
gastrointestinal disease may be challenging.