CONTINUING EDUCATION I SMALL ANIMAL

Canine and feline pancreatitis

Harry Cridge MVB, resident in small animal internal medicine and Alyssa Sullivant
DVM MS DACVIM, assistant professor in small animal internal medicine, Mississippi
State University, College of Veterinary Medicine, present a detailed overview of
canine and feline pancreatitis
Pancreatitis is caused by inflammation of the pancreas, EXOCRINE PANCREAS PHYSIOLOGY
which may be acute or chronic in nature. Pancreatic acinar cells secrete proteolytic digestive
A common differential diagnosis for many patients enzymes in an inactive form called zymogens. Under normal
presenting with gastrointestinal signs, pancreatitis may conditions, these zymogens are secreted into the pancreatic
cause a variety of non-specific clinical signs. duct into the duodenum via hormonal stimulation and
There is a wide spectrum of disease severity, ranging from are only activated within the intestinal lumen. Activation is
very mild to severe. The pathophysiology of pancreatitis is initiated by the enzyme enterokinase, which is released from
not fully understood, although there are a number of well- the duodenal mucosa.
documented predisposing factors to clinical pancreatitis. Enterokinase activates trypsinogen to trypsin, and trypsin can
Pancreatic histopathology is considered the gold standard then activate further zymogens as well as more trypsinogen.4
for diagnosing pancreatitis in dogs;1 however, it is rarely The activated proteolytic enzymes then break down ingesta
performed and the distribution of inflammation in the organ to allow for subsequent absorption of nutrients. As the
may be patchy,2,3 leading to false negative results. zymogens are not activated until they reach the duodenum,
Over the past two decades, a number of non-invasive the normal pancreas is protected from the damage that may
diagnostic assays have been developed to aid in the be caused by the proteolytic enzymes. Enzyme inhibitors, or
diagnosis of pancreatitis, each having its own advantages anti-proteases, also prevent or limit enzyme-induced tissue
and disadvantages. injury to the pancreas.5
Supportive care is the treatment of choice for pancreatitis.
Life-threatening complications, such as disseminated PATHOPHYSIOLOGY
intravascular coagulation (DIC) may develop in severe cases. Pancreatitis develops when trypsinogen is inappropriately

Veterinary Ireland Journal I Volume 8 Number 6 367

SMALL ANIMAL I CONTINUING EDUCATION

activated within the pancreas and overwhelms the protective (SPINK1) gene, which encodes for pancreatic secretory
mechanisms of the acinar cell and anti-proteases within the trypsin inhibitor (PTSI). PTSI acts as a defense mechanism
circulation.6 The initial activation of trypsinogen has been against premature activation of trypsinogen. Mutations in
documented in oxidative stress and hypotension.7 A number the SPINK1 gene are suspected to cause altered protein
of other factors can exacerbate this, including a low pH8 and function, leading to autodigestion of the pancreas.10
a high-calcium9 concentration. Three variants of the SPINK1 gene have been identified
The co-localisation theory helps explain how zymogens can in Miniature Schnauzers and may be associated with the
be prematurely activated within the pancreas. An apical development of pancreatitis in this breed.11
block in the acinar cells prevents the release of zymogen
granules into the intestinal lumen. Zymogen granules and BREEDS
lysosomes, are normally transported to the apex of an acinar Many studies have evaluated the breed prevalence
cell separately; however, the apical block means that the of acute and chronic pancreatitis. The results of these
lysosomes and zymogen granules can fuse prematurely. studies are inconsistent. Breed predispositions are
The fusion allows lysosomal proteases (eg. cathepsin B) to likely a combination of a genetic predisposition for
activate trypsinogen to trypsin. Trypsin can then activate pancreatitis or a predisposition to a predisposing factor
other zymogens, which, once activated, autodigest the (eg. hypertriglyceridemia).4 The majority of cats with acute
pancreatic acinar cells. Activated enzymes ‘escape’ not or suppurative pancreatitis are domestic shorthair cats,
only into the pancreatic tissue, but also into the systemic although Siamese cats are also over represented.12 The most
circulation, causing local and/or systemic side effects. consistently reported at-risk breeds for acute pancreatitis
This tissue damage leads to recruitment of neutrophils include the Miniature Schnauzer, Yorkshire terriers, and other
and macrophages, which release inflammatory cytokines terrier breeds. At-risk breeds for chronic pancreatitis include
that lead to systemic effects, including dehydration, from Boxers, Cavalier King Charles Spaniel, English Cocker
vomiting and diarrhoea, release of vasoactive substances, Spaniels and Collies.13
release of cardio-suppressant substances, and cavitary
effusions. Canine acute pancreatitis • Miniature Schnauzer
As shown in Figure 1, the pathophysiological events of • Yorkshire terrier
pancreatitis can be summarised as a sequence of steps, • Other terrier breeds
starting with an initiating event which leads to characteristic Canine chronic pancreatitis • Boxers
acinar changes (colocalisation) and development of • Cavalier King Charles Spaniel
• English Cocker Spaniel
pancreatitis. The severity and outcome of pancreatitis • Collies
are then determined based on a number of factors
Feline pancreatitis • Domestic shorthair
(inflammatory cytokine release, development of reactive • Siamese
oxygen species and oxidative damage, state and degree of
apoptosis).4 Table 1: Breed predispositions to pancreatitis.

DIET AND OBESITY

Initiating event
Early studies documented that high fat diets induced
pancreatitis in some dogs,14 and that high-fat diets increase
the severity of experimentally-induced pancreatitis in dogs.15
Acinar events Other dietary factors that predispose to pancreatitis include
ingestion of unusual food items (odds ratio 6:1), access to
Severity determinants
table scraps (odds ratio 2:2) and access to trash (odds ratio
Pancreatitis 13:2).16 Obese patients are also predisposed to pancreatitis.

Figure 1: Pathophysiological events in pancreatitis. HYPERTRIGLYCERIDEMIA

Primary hypertriglyceridemia is a risk factor for
PREDISPOSING FACTORS TO PANCREATITIS pancreatitis in Miniature Schnauzers.17,18 The severity of
Dogs and cats of any age, breed, or sex may develop hypertriglyceridemia is important in determining the risk
pancreatitis, but the exact aetiology of a patient’s for pancreatitis, with patients with a serum triglyceride
pancreatitis is rarely definitively confirmed. There are a > 862mg/dl determined to be at an increased risk of
number of well-documented predisposing factors that can pancreatitis in a recent study.17 This link has not been proven
increase a patient’s risk of developing pancreatitis: genetic in other breeds.
factors, breed, diet, obesity, hypertriglyceridemia, endocrine
disorders, and certain drugs. ENDOCRINE DISEASE
Patients with diabetes mellitus, hypothyroidism, and
HEREDITARY PANCREATITIS hyperadrenocorticism are at an increased risk of pancreatitis.
In humans, hereditary pancreatitis may be associated with It is unclear whether the increased risk is due to the disease
mutations of the serine protease inhibitor Kazal-type 1 or due to secondary hypertriglyceridemia.4

368 Veterinary Ireland Journal I Volume 8 Number 6

 CONTINUING EDUCATION I SMALL ANIMAL

DRUGS CLINICAL SIGNS

Due to the low incidence of drug-induced pancreatitis, Due to the absence of pathognomonic clinical signs,
these cases are often considered idiosyncratic drug overlapping clinical signs with other gastrointestinal
reactions.19 Table 2 documents medications that have been diseases, and vague histories, pancreatitis can be
associated with pancreatitis. considered one of the ‘great pretenders’ of small animal
medicine. The majority of patients with pancreatitis,
Anticonvulsants Diuretics especially those with chronic disease, have mild, nonspecific
• Potassium bromide • Furosemide clinical signs, while others can show signs of severe disease
• Phenobarbital • Thiazide diuretics and systemic complications.27
Antimicrobials Others The classic clinical signs of acute, severe pancreatitis vary
• Sulfonamides • Azathioprine in frequency between dogs and cats (see Table 3). In dogs,
• Tetracyclines • Organophosphates
• Estrogen vomiting, abdominal pain, lethargy and dehydration are
• Meglumine antimonate the most common clinical signs. Diarrhoea and fever are
• Salicylates also possible. In general, clinical signs of pancreatitis are
Chemotherapeutics more vague in cats than in dogs, with anorexia or hyporexia,
• L-asparaginase lethargy, dehydration and vomiting being the most common
• Vinca alkaloids clinical signs.28 In cats, abdominal pain, a common clinical
Table 2: Drug-induced pancreatitis.4,19-22 sign in dogs, is reported in only 25% of cases.12 Due to the
unique pancreaticobiliary anatomy in cats, pancreatitis is
MISCELLANEOUS PREDISPOSING FACTORS often associated with triaditis.29 Triaditis is a combination
Abdominal trauma and recent abdominal surgery may of pancreatitis, cholangiohepatitis and inflammatory bowel
predispose to pancreatitis. The pancreas is particularly disease. Clinical signs of these three diseases are often seen
vulnerable to changes in its unique microcirculation.23 together in cats. More severe clinical signs are related to
Similarly, hypotension may predispose4 to or worsen systemic complications of pancreatitis, as discussed below.
pancreatitis. Other miscellaneous predisposing factors
include hypercalcaemia2, obstruction of the pancreatic duct, Canine Vomiting – 90%
and Babesia infections.25 Abdominal pain – 58%
Lethargy
ACUTE AND CHRONIC PANCREATITIS Dehydration
Acute pancreatitis cannot be clinically distinguished from Feline Inappetence – 83%
Lethargy – 77%
chronic pancreatitis; however, chronic pancreatitis cases Dehydration – 65%
tend to have milder clinical signs. Acute pancreatitis is Vomiting – 43%
defined as reversible inflammation of the pancreas with Icterus – 29%
histological evidence of oedema, neutrophilic infiltration Abdominal pain – 25%
and necrosis.13 Chronic pancreatitis, however, is defined Weight loss – 16%
as having irreversible changes, such as fibrosis.13 There are Table 3: Clinical signs of acute pancreatitis in dogs and cats.12,28,30
two ways a patient may develop chronic pancreatitis, as
highlighted in Figure 2. While some cases of pancreatitis SEQUELAE/COMPLICATIONS OF PANCREATITIS
can be considered chronic from the outset due to LOCALISED COMPLICATIONS
lymphoplasmacytic infiltration, other cases of chronic Localised complications of pancreatitis result from the
pancreatitis develop from failure of acute pancreatitis to release of activated digestive enzymes into the pancreas
completely resolve.26 and surrounding tissue, resulting in peritonitis and, possibly,
necrosis of adjacent organs. Pancreatic inflammation
Patient may also extend into the endocrine pancreas and lead
to development of diabetes mellitus. Hyperglycaemia
in a patient with previous or current pancreatitis should
prompt suspicion of diabetes and warrants further
Acute pancreatitis Chronic pancreatitis
investigation and monitoring. Pancreatitis may cause both
peritoneal and pleural effusions. Obstruction of the bile
duct and post-hepatic hyperbilirubinaemia are additional
complications of severe pancreatitis. Pancreatic abscesses
Recurrent acute and pseudocysts have also been reported as sequelae
Resolves pancreatitis to pancreatitis. A detailed discussion of management of
pancreatic pseudocysts, pancreatic abscesses and necrotic
Figure 2: Relationship between acute and chronic pancreatitis. masses is beyond the scope of this review; however, readers
are encouraged to read a recent review by Coleman and
Robson.31

Veterinary Ireland Journal I Volume 8 Number 6 369

SMALL ANIMAL I CONTINUING EDUCATION

SYSTEMIC COMPLICATIONS MOVING BEYOND TRADITIONAL LIPASE AND

Release of digestive enzymes, or proteases, into the AMYLASE
systemic circulation can result in hypotension, systemic Although used historically for the diagnosis of pancreatitis,
inflammatory response syndrome (SIRS) and multi-organ lipase and amylase have a poor sensitivity and specificity.34,36
dysfunction syndrome (MODS). Inflammatory cytokines, Serum lipase measures total lipase (ie. lipase of pancreatic,
oxidative substances, and proteolytic enzymes allow for hepatic and gastric-cells origin), whereas pancreatic lipase
such extreme progression of pancreatitis and development assays measure lipase of pancreatic acinar cell origin only.37
of multiple organ failure.2,32 Arrhythmias, myocardial Therefore, pancreatic lipase is expected to be increased
depression, ileus, pre-renal or renal azotemia, DIC, and only during times of active pancreatic inflammation.
non-cardiogenic pulmonary oedema may develop in severe
cases.32 CANINE ASSAYS
The SNAP cPL is a rapid in-house test that is reported
DIAGNOSIS – TRADITIONAL GOLD STANDARD VS as either normal or abnormal. Normal results indicate
CLINICAL GOLD STANDARD a pancreatic lipase concentration <200mg/L and can
TRADITIONAL GOLD STANDARD rapidly rule out pancreatitis. Abnormal (or positive) results
Pancreatic histopathology is considered the traditional indicate a pancreatic lipase concentration³ 200mg/L and
gold standard and most reliable method for diagnosing should be followed by the Spec cPL.4 If the sample ‘spot’
pancreatitis.1 However, pancreatic histopathology is rarely is equal in color to the reference spot, the pancreatic
performed due to its invasive nature. Pancreatic biopsies lipase concentration is between 200-399mg/L; this is
also have a number of limitations, including the potential equivocal for the diagnosis of pancreatitis. If the sample
to miss highly localised lesions of pancreatitis,2,3 a lack of spot is darker than the reference spot, then the pancreatic
standardised criteria for interpretation, and detection of lipase concentration is³ 400mg/L, which is consistent with
subclinical pancreatitis.2 a diagnosis of pancreatitis. The Spec cPL is a quantitative,
send-out test for measurement of canine pancreatic lipase;
CLINICAL GOLD STANDARD it is useful to confirm pancreatitis and can be monitored
In the absence of a practical and clinically justifiable during or after therapy. The disadvantage of this test is
reason to obtain pancreatic biopsies, many clinicians, elect that the results take >24 hours to return, thereby delaying
to pursue a clinical diagnosis of pancreatitis based on a diagnosis. The VetScan cPL Rapid Test is a newer
analysis of a comprehensive body of information including; diagnostic assay that offers the combined benefit of a
signalment, history, physical examination, complete blood rapid in-house result and a specificity similar to, or greater
count (CBC), serum biochemistry, abdominal ultrasound and than, the established Spec cPL assay.33 There are currently
a pancreatic lipase assay. Recent publications support this no published validation studies for the VetScan cPL Rapid
more practical approach.33-35 Test. To the authors’ knowledge, the Precision PSL, a DGGR
(1,2-o-dilauryl-rac-glycero-3-glutaric acid 6’-methyl-resorufin
CBC AND SERUM BIOCHEMISTRY ABNORMALITIES ester) based assay, is not commercially available in the UK/
IN PANCREATITIS Republic of Ireland. It is non-specific for pancreatic lipase.38
CBC abnormalities found with pancreatitis are relatively
non-specific. Patients with severe pancreatitis can develop FELINE ASSAYS
a neutrophilia with a left shift. Thrombocytopaenia and There are fewer commercially available pancreatic
anaemia may occur, especially in the presence of DIC. lipase assays available for cats. The SNAP fPL is an in-
Haemoconcentration, due to fluid losses may be noted house assay. Normal results indicate a feline pancreatic
initially. Pre-renal (due to dehydration) and renal azotemia lipase concentration <3.5mg/L and can rapidly rule out
elevated liver enzymes, hypoalbuminemia, hyponatraemia, pancreatitis. Abnormal (or positive) results indicate a
hypokalaemia, hyperbilirubinaemia, hyperlipidaemia and pancreatic lipase concentration³ 3.5mg/L. If the sample
hypocalcaemia (due to saponification of peri-pancreatitic spot is equal in color to the reference spot, then the
fat) may occur. Potential bloodwork findings are summarised pancreatic lipase concentration is considered between 3.5-
in Table 4. 5.4mg/L; this is equivocal for the diagnosis of pancreatitis.
If the sample spot is darker than the reference spot, the
CBC Serum biochemistry pancreatic lipase concentration is considered³ 5.4mg/L,
• Neutrophilia with left shift • Azotemia which is consistent with a diagnosis of pancreatitis. The Spec
• Thrombocytopenia and mild • ALT and ALP elevation fPL is a quantitative send-out assay similar to the canine
anaemia • Hyperbilirubinaemia Spec cPL.
• Haemoconcentration • Hypocalcaemia, hyponatraemia,
• Hyperproteinaemia (initially due and/or hypokalaemia
to haemoconentration) • Hypoalbuminaemia DIAGNOSTIC IMAGING
• Hyperlipidaemia Radiographs have a poor sensitivity and specificity for the
diagnosis of pancreatitis in dogs and cats. Radiographic
Table 4: CBC and serum biochemistry abnormalities in pancreatitis. signs of pancreatitis include a gas-filled duodenum
(duodenal stripe), displacement of the proximal duodenum

370 Veterinary Ireland Journal I Volume 8 Number 6

 CONTINUING EDUCATION I SMALL ANIMAL

Total lipase SNAP cPL Spec cPL VetScan cPL rapid test Precision PSL
Sensitivity (%) 54.0 73.9-100 81.0-90.9 73.9-83.3 85.7-90.9
Specificity (%) 43.0 71.1-77.8 74.1-81.1 76.9-83.8 64.0-74.3
Recommended use - Screening Confirmatory Confirmatory Screening
In house/send out Send out In house Send out In house Send out
Availability in UK/ROI Yes Yes Yes Yes No

Table 5: Diagnostic assays for pancreatitis in dogs.33,36

and pylorus to the right, and evidence of abdominal FLUID THERAPY

effusion. The diagnostic sensitivity of ultrasound is around Intravenous fluids are important for maintenance of
68% but varies greatly depending on ultrasonagrapher pancreatic micro-perfusion and help to slow progression
experience.1 Characteristic ultrasonographic signs of of pancreatitis. Balanced isotonic electrolyte solutions
pancreatitis include enlargement or irregularity of the such as lactated Ringer's solution (LRS) are appropriate
pancreas, hypoechoic areas within the pancreas and/or a first choice fluids in pancreatitis. Fluid rates should be
hyperechoic mesentery surrounding the pancreas. calculated to correct the fluid deficit over 12-24 hours (within
the physiological demands of each patient) followed by a
TREATMENT taper to maintenance fluid rates. Patient losses (vomiting,
Mild cases are frequently managed on an outpatient basis diarrhoea, cavitary effusions) must also be accounted
(antiemetics and pain medication), whereas moderate-to- for and normal blood pressure should be maintained to
severe cases with systemic consequences often require ensure adequate pancreatic perfusion. Electrolytes should
in-hospital management. As with many conditions, disease be monitored, and supplementation should be given
severity is inversely proportional to prognosis. There are no accordingly. Colloids may be indicated for hypotension and/
specific treatments for canine or feline pancreatitis, and as or severe hypoalbuminemia.
such, supportive care is the treatment of choice.
PLASMA TRANSFUSIONS
Disease severity Plasma transfusions for pancreatitis have been explored in
both human and veterinary medicine. There are two main
theoretical benefits to plasma transfusions in pancreatitis.
Firstly, many pancreatitis patients are hypoalbuminaemic,
Mild Moderate Severe and therefore, a plasma transfusion may provide colloidal
support. However, fresh-frozen plasma (FFP) is relatively
low in albumin, and a significant volume of plasma would
Excellent Good-to-guarded Poor be required to correct or substantially improve the
hypoalbuminaemia. In addition, other transfusion products
such as cryo-poor plasma (CPP) are more cost-effective
and higher in albumin than FFP39 and are not used in
Prognosis
the management of pancreatitis. The second argument
for plasma in pancreatitis, is that plasma contains anti-
Figure 3: Relationship between disease severity and prognosis. proteases which are depleted in pancreatitis (eg. alpha-

Veterinary Ireland Journal I Volume 8 Number 6 371

SMALL ANIMAL I CONTINUING EDUCATION

macroglobulins and anti-trypsins).40 On the other hand, buprenorphine should be considered. Non-steroidal anti-
studies have documented that, despite a decrease in alpha inflammatory drugs (NSAIDs) should be avoided.
macroglobulins in pancreatitis the severity of decrease
does not correspond with clinical severity. A recent study NUTRITION – TO FEED OR NOT TO FEED?
also documented a higher mortality rate in pancreatitis Traditionally, fasting pancreatitis patients was a mainstay
dogs receiving FFP compared to those that did not, of acute pancreatitis treatment,1 based on the theory that
concluding there was no benefit to administering FFP in it this would avoid pancreatic stimulation and premature
canine pancreatitis.41 Similar results have been documented activation of zymogens. However, there is now a large body
in large, human clinical trials.42 It is, therefore, the authors’ of data in human medicine that documents decreased
opinion that, until further evidence is published, plasma morbidity and mortality from pancreatitis with early
transfusions should be reserved for pancreatitis patients enteral nutrition. Based on clinical evidence in humans,
with documented coagulopathies. experimental animal studies, and preliminary studies in
dogs and cats, early enteral feeding during pancreatitis is
ANTIEMETICS encouraged.44 A recent clinical practice review concluded
Antiemetics should be used to treat vomiting and that enteral nutrition in dogs and cats with acute pancreatitis
reduce nausea-associated inappetence. Commonly used is beneficial and well tolerated.44 Enteral feeding is
anti-emetics include maropitant citrate (Cerenia) and strongly recommended in cats to prevent complications of
ondansetron (Zofran). Metoclopramide (Reglan) or cisapride inappetence such as hepatic lipidosis. A detailed discussion
(Propulsid) may also be indicated, especially if ileus is of feeding recommendations for pancreatitis is beyond the
present. scope of this review; however, readers are encouraged to
read a recent review by Justin Shmalberg.5
ANALGESIA
Pancreatitis may cause severe abdominal pain, and OTHER MEDICATIONS
analgesia is key to its successful management. It is Proton pump inhibitors (omeprazole) or H2-receptor
important to recognise that clinical signs of pain are antagonists (famotidine, ranitidine) are useful adjunctive
often underappreciated in feline patients, and that pain medications and may decrease the risk of gastric or
assessments must be based on behavioural assessment intestinal ulceration or oesophagitis.
rather than objective measures such as heart rate.43
Opioid analgesics, such as methadone, fentanyl, and REFERENCES ON REQUEST

READER QUESTIONS AND ANSWERS

1: WHAT IS THE MOST COMMON CLINICAL SIGN OF ACUTE 4: WHICH OF THE FOLLOWING IS NOT AN APPROPRIATE
PANCREATITIS IN DOGS? ANALGESIC FOR PANCREATITIS?
A Abdominal pain A Methadone
B Vomiting B Fentanyl
C Diarrhoea C Buprenorphine
D Inappetence D Carprofen

2: WHAT IS THE MOST COMMON CLINICAL SIGN OF ACUTE 5: WHICH OF THE FOLLOWING STATEMENTS IS CORRECT?
PANCREATITIS IN CATS? A All cases of pancreatitis have a good prognosis with
A Abdominal pain medical management
B Vomiting B Patients with pancreatitis should be fasted for 24
C Diarrhoea hours
D Inappetence C All cases of pancreatitis require in-hospital
management
3: WHICH OF THE FOLLOWING TESTS HAS THE HIGHEST D Enteral nutrition is preferred over parenteral nutrition
SPECIFICITY FOR THE DIAGNOSIS OF PANCREATITIS IN in the management of pancreatitis
DOGS?
A Abdominal ultrasound
B SNAP cPL
C Spec cPL
D Serum lipase
ANSWERS: 1:B; 2:D; 3:C; 4:D; 5:D

372 Veterinary Ireland Journal I Volume 8 Number 6