Confused about Lipase Assays?
The measurement of pancreatic lipase immunoreactivity (PLI; as
measured by Spec cPL® in dogs and Spec fPL®
in cats) has become the standard for the diagnosis of acute and
chronic pancreatitis in either species. While no diagnostic test is
100% sensitive and specific, these assays have been repeatedly
shown to be far superior to the measurement of serum lipase
activity. Recently, catalytic assays for the measurement of serum
lipase activity have been marketed with claims of comparable
diagnostic utility to the measurement of serum PLI concentrations.
While these assays utilize substrates other than the traditional
1,2 diglyceride (i.e., triolein in the case of v-Lip-P and DGGR in
the case of PrecisionPSLTM Pancreatic Sensitive Lipase
and several others), none of these other substrates are entirely
specific for the measurement of pancreatic lipase and consequently
they may detect other lipases that do not originate from the
exocrine pancreas. Therefore, the only assays that are specific for
the measurement of pancreatic lipase remain Spec cPL and Spec fPL.
Please let us know if you have any questions regarding lipase
Pancreatitis, an inflammatory condition of the exocrine
pancreas, occurs frequently in both dogs and cats. While the true
prevalence of pancreatitis in dogs and cats is unknown, recent
studies would suggest that pancreatitis is a rather common and
underdiagnosed condition in both dogs and cats. In a large
retrospective study of necropsy findings 1.5% of 9,342 canine and
1.3% of 6,504 feline pancreata showed important pathological
lesions. Pancreatitis can be difficult to diagnose. This may be due
to the non-specific clinical signs commonly displayed by
pancreatitis patients. However, there also has been a lack of
diagnostic tests for pancreatitis that are both sensitive and
specific for pancreatitis.
Clinical signs of dogs and cats with pancreatitis depend on the
severity of the disease. Mild cases may remain subclinical while
more severe cases may present with a wide variety of clinical
signs. In a recent retrospective study of 70 dogs with fatal
pancreatitis the following clinical signs were reported: anorexia
in 91% of the cases, vomiting in 90%, weakness in 79%, abdominal
pain in 58%, dehydration in 46%, and diarrhea in 33%. These
findings are somewhat surprising as abdominal pain is the key
clinical sign of pancreatitis in human patients. Thus, the question
arises whether dogs with pancreatitis have abdominal pain less
frequently than humans, or more likely, whether we fail to
correctly identify abdominal pain. It also should be recognized
that retrospective studies could underestimate the true prevalence
of abdominal pain due to lack of reporting, difference in
investigator, or other factors. Classically, diarrhea has not been
described as a typical clinical sign of pancreatitis. However, with
33% of dogs with pancreatitis in this study having diarrhea it
would seem prudent to assess any dog presenting with diarrhea for
potential pancreatitis during a systematic work-up.
Cats, even with severe pancreatitis, present with less specific
clinical signs than do dogs. In a recent review of a large number
of cats with pancreatitis the following clinical signs were
reported: anorexia in 87%, lethargy in 81%, dehydration in 54%,
weight loss in 47%, vomiting and hypothermia in 46%, icterus in
37%, fever in 25%, abdominal pain in 19%, diarrhea in 12%, and a
palpable abdominal mass in 11%. Especially remarkable in this
report is the low incidence of vomiting and abdominal pain in cats
Clinical signs in patients with pancreatitis are either due to
activity of prematurely activated pancreatic enzymes or to systemic
effects of the inflammatory response to pancreatic autodigestion.
Recent data suggest that the exocrine pancreas responds to many
different noxious stimuli in a similar fashion. The first common
change reported is a decrease in secretion of pancreatic enzymes.
This is followed by the formation of giant cytoplasmic vacuoles in
acinar cells, visible only by electron microscopy. Biochemical
studies have shown that these vacuoles are the product of
co-localization of zymogens of digestive enzymes and lysosomal
enzymes, which are normally strictly segregated. The ensuing
decrease in pH and/or the presence of the lysosomal enzymes such as
cathepsin B lead to premature activation of trypsinogen. Trypsin in
turn activates other zymogens, leading to local effects such as
inflammation, pancreatic edema and hemorrhage, pancreatic necrosis,
and parapancreatic fat necrosis. These local effects are associated
with clinical signs such as vomiting and abdominal pain.
Until recently it was believed that systemic signs seen in
pancreatitis patients, like local effects, are a direct result of
circulating pancreatic enzymes. While there is little doubt that
some of these systemic effects, such as systemic lipodystrophy, are
caused by circulating pancreatic enzymes, recent data would suggest
that other systemic sequelae are a consequence of the release of
inflammatory mediators in response to pancreatic inflammation.
Systemic effects seen in patients with severe pancreatitis include
fever, systemic vasodilation leading to hypotension and sometimes
acute renal failure, pulmonary edema leading to respiratory
failure, disseminated intravascular coagulation, and in some cases
multi-organ failure. A few patients also develop systemic
lipodystrophy. Neurologic signs such as disorientation have been
seen in human, canine, and feline patients with severe pancreatitis
and are sometimes referred to as pancreatic encephalopathy. While
clinical signs are not specific for pancreatitis, vomiting,
anorexia, and cranial abdominal pain are key clinical signs in dogs
with pancreatitis. Cats display these key clinical signs less
frequently and a conclusive diagnosis of pancreatitis in this
species is much more difficult to arrive at.
General clinical pathology
Complete blood count and serum chemistry profile often show mild
and nonspecific changes. While these findings maybe useful in the
overall assessment of the health status of the patient, they are
not useful for arriving at a specific diagnosis of pancreatitis in
either dogs or cats.
Changes seen on abdominal radiographs may include a decreased
contrast in the cranial abdomen and displacement of abdominal
organs. However, these changes are rather subjective and abdominal
radiography is non-specific for canine or feline pancreatitis.
However, abdominal radiographs are crucial in ruling out other
differential causes of acute-onset vomiting and anorexia, such as
an obstruction due to a foreign body.
Abdominal ultrasound was first described as a diagnostic tool
for pancreatitis in the mid-80ties. Since then both the technology
and expertise of veterinary radiologists in this area have markedly
increased. While this development has led to a significant increase
in sensitivity of this diagnostic modality for pancreatitis it has
also led to a decrease in specificity. The sensitivity of abdominal
ultrasonography for pancreatitis when performed by a veterinary
radiologist has been reported to be up to 68% in dogs and up to 35%
in cats. Changes identified include pancreatic enlargement, changes
in echogenicity of the pancreas (hypoechogenicity is generally
believed to be an indication of pancreatic necrosis and
hyperechogenicity that of pancreatic fibrosis) and of
peripancreatic fat (hyperechogenicity of the peripancreatic fat is
generally believed to indicate peripancreatic fat necrosis), fluid
accumulation around the pancreas, a mass effect in the area of the
pancreas, a dilated pancreatic duct, and a swollen major duodenal
papilla. When stringent criteria are applied abdominal
ultrasonography is useful for the diagnosis of pancreatitis in both
dogs and cats.
Abdominal computed tomography is a routine procedure used in
humans suspected of having pancreatitis, but appears to be very
insensitive for the diagnosis of pancreatitis in the cat and data
in dogs are extremely limited.
Minimally-invasive diagnostic tests
Many minimally invasive diagnostic tests for canine and feline
pancreatitis have been described, but few have been found to be
Serum lipase activity
Serum lipase activity has been used for the diagnosis of human
and canine pancreatitis for several decades. However, it has long
been recognized that serum lipase activity is neither very
sensitive nor very specific for pancreatitis in either species.
Serum lipase activity has been reported to decrease in dogs
after pancreatectomy, indicating that some of the lipase activity
present in the serum does originate from the exocrine pancreas.
However, considerable serum lipase activity is still present in
these dogs after pancreatectomy, indicating that lipase activity
must originate from additional sources. It should be noted that
there are many cell types that synthesize and secrete lipases.
These lipases of different cellular origins share a common function
and thus can not be differentiated by use of a catalytic assay such
as the ones that are being used to determine lipase activity in
serum. To further illustrate this phenomenon serum lipase activity
was measured in dogs with exocrine pancreatic insufficiency (EPI).
These dogs have no significant pancreatic functional reserve yet in
this group of 25 dogs with EPI mean serum lipase activity did not
differ significantly from that in 74 healthy dogs and only one dog
with EPI had a decreased serum lipase activity below the lower
limit of the reference range.
In addition, many non-pancreatic conditions are associated with
a significant increase in serum lipase activity, leading to
false-positive results. In summary, serum lipase activity is
neither very sensitive nor very specific for diagnosing
pancreatitis in dogs and should thus only be used if an in-house
assay is available and until the diagnosis can be confirmed by
another, more specific, diagnostic modality. Finally, if serum
lipase activity is analyzed it should be interpreted cautiously and
only elevations of 3-5 times the upper limit of the reference range
should be considered suggestive of pancreatitis.
In one study not a single cat with pancreatitis had a serum
lipase activity above the upper limit of the reference range. These
data would suggest that serum lipase activity is of no clinical
usefulness for the diagnosis of pancreatitis in cats.
Serum amylase activity
The diagnostic utility of serum amylase activity for canine and
feline pancreatitis is very similar to that of serum lipase
activity. Some dogs with spontaneous pancreatitis have an elevated
serum amylase activity, but others have serum amylase activities in
the normal range. Furthermore, dogs with non-pancreatic conditions
can have elevations of serum amylase activities. In contrast to its
effect on serum lipase activity, the administration of prednisone
and dexamethasone to clinically healthy dogs led to a decrease in
serum amylase activity. These data would suggest that, as for serum
lipase activity, serum amylase activity should only be used for the
diagnosis of pancreatitis if an in-house assay is available and
until the diagnosis can be confirmed by more accurate diagnostic
In a study serum amylase activity was not significantly
different between cats with spontaneous pancreatitis, clinically
healthy cats, and cats with non-pancreatic diseases. This would
suggest that serum amylase activity has no clinical usefulness in
the diagnosis of pancreatitis in cats.
Serum trypsin-like immunoreactivity (TLI) is an assay that
mainly measures trypsinogen in serum, but will also detect trypsin
and some trypsin molecules bound to proteinase inhibitors. During
health a small amount of trypsinogen is secreted into the vascular
space but very little or no trypsin is present in serum during
health. Serum TLI has been shown to originate from the exocrine
pancreas almost exclusively. Similar studies are not available for
cats, but as in dogs no evidence is available that would suggest
that serum TLI concentration can originate from cells other than
pancreatic acinar cells.
Only 30-60% of dogs and cats with spontaneous pancreatitis have
an elevated serum TLI concentration. This is most likely due to the
sort half-life of serum TLI concentration.
Recently, assays for measurement of pancreatic lipase
immunoreactivity in dogs and cats (cPLI and fPLI, respectively)
have been developed and validated. As mentioned previously, many
different cell types in the body synthesize and secrete lipases. In
contrast to catalytic assays for the measurement of lipase
activity, use of immunoassays does allow for the specific
measurement of lipase originated from the exocrine pancreas.
Serum cPLI was measured in a group of dogs with exocrine
pancreatic insufficiency and the median serum cPLI concentration
was significantly decreased compared to clinically healthy dogs. In
addition, serum cPLI concentration was non-detectable in most of
the dogs, indicating that serum cPLI concentration mostly, if not
exclusively, originates from the exocrine pancreas. The sensitivity
of different minimally-invasive diagnostic tests was compared in
dogs with biopsy-proven pancreatitis. The sensitivity of serum TLI
concentration was below 35% and that of serum lipase activity was
less than 55%. In contrast, the sensitivity for serum cPLI
concentration for pancreatitis was above 80%.
In another study of cats with spontaneous pancreatitis serum
fPLI concentration was more sensitive and more specific than serum
fTLI concentration or abdominal ultrasonography.
These initial data would suggest that serum PLI concentration is
highly sensitive and specific for the diagnosis of pancreatitis in
dogs and cats. Commercial assays for measurement of cPLI (Spec
cPL™) and fPLI (Spec fPL™) are based on the original cPLI and fPLI
technology and are available through the GI Lab.
Traditionally, a pancreatic biopsy has been viewed as the most
definitive diagnostic tool for pancreatitis. The presence of
pancreatitis can sometimes be easily determined by gross appearance
of the pancreas. However, the absence of pancreatitis can be
difficult to prove. In a recent study histopathological findings in
dogs with pancreatitis were highly localized, suggesting that even
if multiple biopsies are being collected, pancreatic inflammation,
especially in cases of chronic pancreatitis, may be easily missed.
It should also be noted that while a pancreatic biopsy in itself is
not associated with many complications many patients with
pancreatitis are poor anesthetic risks. In some patients pancreatic
biopsy may be useful for the differentiation of pancreatitis and
exocrine pancreatic neoplasia.
Dr. Jörg M. Steiner
- Newman SJ, Steiner JM, Woosley K, et al. Localization of
histologic pancreatitis lesions in dogs. J Vet Int Med
- Forman MA, Marks SL, De Cock HEV, et al. Evaluation of serum
feline pancreatic lipase immunoreactivity and helical computed
tomography versus conventional testing for the diagnosis of feline
pancreatitis. J Vet Int Med 2004; 18:807-815.
- Steiner JM, Gumminger SR, Rutz GM, et al. Serum canine
pancreatic lipase immunoreactivity (cPLI) concentrations in dogs
with exocrine pancreatic insufficiency. J Vet Int Med
- Steiner JM, Broussard J, Mansfield CS, et al. Serum canine
pancreatic lipase immunoreactivity (cPLI) concentrations in dogs
with spontaneous pancreatitis. J Vet Int Med 2001;15:274