Content uploaded by Sheikh Bilal Ahmad
Author content
All content in this area was uploaded by Sheikh Bilal Ahmad on Jan 18, 2018
Content may be subject to copyright.
~509~
The Pharma Innovation Journal 2017; 6(12): 509-516
ISSN (E): 2277- 7695
ISSN (P): 2349-8242
NAAS Rating 2017: 5.03
TPI 2017; 6(12): 509-516
© 2017 TPI
www.thepharmajournal.com
Received: 15-10-2017
Accepted: 17-11-2017
Saima Mushtaq
Faculty of Veterinary Sciences & Animal
Husbandry, Sheri Kashmir University of
Agricultural Science & Technolog y (SKUAST-
K), Alustang, Sh uhama, Srinagar, J&K, India
Iqra Farooq
Faculty of Veterinary Sciences & Animal
Husbandry, Sheri Kashmir University of
Agricultural Science & Technolog y (SKUAST-
K), Alustang, Sh uhama, Srinagar, J&K, India
Insha Farooq
Faculty of Veterinary Sciences & Animal
Husbandry, Sheri Kashmir University of
Agricultural Science & Technolog y (SKUAST-
K), Alustang, Sh uhama, Srinagar, J&K, India
Shahzada Mudasir Rashid
Molecular Biology Lab, Division of Veterina ry
Biochemistry, Faculty of Veterinary Sciences &
Animal Husbandry, Sheri Kashmir University
of Agricultural Science & Technolo gy
(SKUAST-K), Alustang, Shuhama, Srinagar,
J&K, India
Muneeb U Rehman
Molecular Biology Lab, Division of Veterina ry
Biochemistry, Faculty of Veterinary Sciences &
Animal Husbandry, Sheri Kashmir University
of Agricultural Science & Technolo gy
(SKUAST-K), Alustang, Shuhama, Srinagar,
J&K, India
Rayeesa Ali
Division of Veterinary Pa thology, Faculty of
Veterinary Sciences & Animal Husbandry, Sheri
Kashmir University of Agricultural Science &
Technology (SKUAST-K), Alustang, Shuhama,
Srinagar, J&K, India
Mir Shabir
Division of Animal Gene tics and Breeding,
Faculty of Veterinary Sciences & Animal
Husbandry, Sheri Kashmir University of
Agricultural Science & Technolog y (SKUAST-
K), Alustang, Sh uhama, Srinagar, J&K, India
Manzoor Ur Rahman Mir
Molecular Biology Lab, Division of Veterina ry
Biochemistry, Faculty of Veterinary Sciences &
Animal Husbandry, Sheri Kashmir University
of Agricultural Science & Technolo gy
(SKUAST-K), Alustang, Shuhama, Srinagar,
J&K, India
Sheikh Bilal Ahmad
Molecular Biology Lab, Division of Veterina ry
Biochemistry, Faculty of Veterinary Sciences &
Animal Husbandry, Sheri Kashmir University
of Agricultural Science & Technolo gy
(SKUAST-K), Alustang, Shuhama, Srinagar,
J&K, India
Correspondence
Dr. Shahzada Mudasir Rashid
Assistant Professor, Molecular Biology Lab,
Division of Veterinary Bio chemistry, Faculty of
Veterinary Sciences & Animal Husbandry, Sheri
Kashmir University of Agricultural Science &
Technology (SKUAST-K), Alustang, Shuhama,
Srinagar, J&K, India
Acute pancreatitis in dogs: A review
Saima Mushtaq, Iqra Farooq, Insha Farooq, Shahzada Mudasir Rashid,
Muneeb U Rehman, Rayeesa Ali, Mir Shabir, Manzoor Ur Rahman Mir
and Sheikh Bilal Ahmad
Abstract
Acute pancreatitis is the more clinically recognized form of inflammation in pancreas. Failure of
zymogens activation causes inflammation and necrosis of the pancreatic tissue thereby resulting in
leakage of pancreatic digestive enzymes into the peritoneal space or the intravascular space. Chances of
disease occurrence varies with respect to age, breeds etc. Dogs with acute pancreatitis attain “praying
position” or “position of relief” in response to cranial abdominal pain. In addition, there is vomiting,
anorexia and depression. Blood examination shows peripheral blood neutrophilia with a degenerative left
shift, anemia and thrombocytopenia. Azotemia, hyperbilirubinemia, hypocalcemia, hyperglycemia and
eleveted levels of liver enzymes are usual findings. Disease is diagnosed by radiography,
ultrasonography, Computed tomography and immunological tests. Fluid therapy, plasma, analgesics,
antiemetics are generally recomended. Also, dogs are provided healthy diet.
Keywords: Dogs, Pancreatitis, Neutrophillia and inflammation
Introduction
The pancreas is a flat, thin organ located in an abdomen, caudal to the stomach and is
composed of a left limb or lobe, which lies behind the greater curvature of the stomach and
adjacent to the cranial aspect of the transverse colon; a right limb or lobe which lies just
medial to the proximal duodenum and a body between these two limbs (Saunders, 1991;
Evans, 1993) [59, 17]. It is composed of two major types of cells responsible for both endocrine
and exocrine roles. The endocrine function is localized in distinct islet of langerhans that
constitute less than 1% to 2% of the pancreas (Evans, 1993) [17] and produce hormones
required to regulate glucose and to some extent lipid metabolism. The islets of langerhans
constitute four different types of cells namely, the alpha cells which secrete glucagon, beta
cells secrete insulin, gamma cells secrete somatostatin and delta cells secrete pancreatic
polypeptidase. The exocrine part, constitutes about 98% is composed of acinar cells and
ductular cells. The major function of the exocrine pancreas is production, storage, and
secretion of digestive enzymes important for degradation of ingested proteins, fats, and
polysaccharides which are subsequently released into the stomach and/or small intestine as
food reaches these organs (Williams, 2000) [82]. The digestive enzymes produced by the
pancreatic acinar cells, are stored until the pancreas is stimulated to secrete them into the
duodenum.
The ductal system in dog consists of 2 ducts; the pancreatic duct, which lies adjacent to the
common bile duct just before it enters the duodenum through the major duodenal papilla and
the accessory pancreatic duct which enters the duodenum at the level of minor papilla (Evans,
1993) [17].
Pancreatitis And Its Pathophysiology
Pancreatitis was first described by Dr. Reginald Fitz in 1889. Pancreatitis is inflammation of
the Pancreas and can be acute or chronic. Both acute and chronic forms of pancreatitis occur in
dogs, with the acute form being more clinically recognized (Williams, 2000; Van Den
Bossche, 2010) [84, 73]. Acute pancreatitis is usually sterile inflammation with acute onset and
characterized by necrosis and edema; which doesn’t permanently disrupt the pancreatic
architecture and is completely reversible. Acute pancreatitis is thought to occur primarily
because of inappropriate activation of zymogens to their active forms within the pancreas,
thereby resulting in autodigestion, pancreatic inflammation and necrosis of the pancreatic
tissue (Williams, 2000) [84].
~510~
The Pharma Innovation Journal
Depending on the severity of inflammation, pancreatic edema
may occur, resulting in leakage of pancreatic digestive
enzymes into the peritoneal space or the intravascular space.
In the initial stages the body is able to protect itself from
damage due to the limited supply of alpha- macroglobulins
and other protease inhibitors in systemic circulation by
binding to the leaked digestive enzymes, thereby inactivating
them and expediting their removal from the body. Once this
limited supply is exhausted, there is widespread inflammation
and activation of the coagulation, fibrinolytic and complement
cascades due to the circulating digestive enzymes.
Disseminated intravascular coagulation, shock, and
multiorgan failure (Williams, 1996) [83] may also develop in
the affected animals.
The exact mechanism by which acute pancreatitis develops is
still incompletely understood. Normally, to prevent
autodigestion various pancreatic defense mechanisms exist.
Proteolytic enzymes are synthesized and secreted in the form
of catalytically inactive precursors called zymogens (for
example trypsinogen) (Steiner, 2003a; Watson, 2004; Mix
and Jones, 2006) [67, 76, 52]. In the acinar cell, storage of
zymogens in granules prevents their damage by lysosomal
proteases (Watson, 2004; Mix and Jones, 2006) [76, 52].
Cleavage of a small amino terminal peptide called trypsin
activation peptide (TAP) of the polypeptide chain, causes
activation of zymogens, but this normally does not occur until
they are secreted into the small intestine. Trypsinogen is the
first zymogen to be activated, which is cleaved by brush
border enzyme enteropeptidase (previously enterokinase)
synthesized by the enterocytes of the duodenal mucosa to
form trypsin (Watson, 2004; Mix and Jones, 2006) [76, 52].
Recently, chymotrypsin C, an another pancreatic enzyme, has
also been implicated in activating or inactivating trypsinogen
in the small intestine, depending on the calcium concentration
of the environment (Szabo et al., 2012) [71]. Calcium
concentration being high within the pancreatic duct and small
intestinal lumen but very low in the acinar cells, favour
trypsin activation (LaRusch and Whitcomb, 2011) [39].
However activation of trypsin is also pH dependent: although
trypsin requires a relatively high pH to function (i.e. the
alkaline pH of the small intestine), its activation appears to be
exquisitely pH sensitive. Trypsin plays predominant role in
the activation cascade by cleaving the activation peptides
from the other zymogens and itself (Watson, 2004; Mix and
Jones, 2006) [76, 52]. Damage caused due to inappropriate early
intra-pancreatic activation of proteases is prevented by two
mechanisms. The first mechanism involves small amounts of
trypsin that can hydrolyze itself (Watson, 2004) [76] or a low-
molecular-weight molecule pancreatic secretory trypsin
inhibitor (PSTI), present in the zymogens can inactivate
approximately 10 percent of the total amount of trypsin by
temporarily binding to it (Watson, 2004; Mix and Jones,
2006) [76, 52]. Another protection mechanism against the
possible fatal effects of protease release in the vascular space
is played by plasma protease inhibitors. Alpha-
macroglobulins (α-M1 and α-M2) and α1-proteinase
inhibitors (α-1-antitrypsin) inhibit neutrophil elastase and
form complexes with proteases, which are then removed from
the plasma by the reticulo-endothelial system. This removal is
crucial, because the bound proteases retain their proteolytic
activity (Steiner, 2003) [65]. A cascade of early activation of
zymogens, especially proelastase and prophospholipase is
initiated by premature activation of trypsin in the acinar cells
where the developing granules are normally kept strictly
separated from lysosomes and might inadvertently get
activated (Bunch, 2003;Watson, 2004) [9, 76]. Zymogen
granules abnormally fuse with lysosomes which contain
proteases, due to disturbance in cellular metabolism or an
increase in the permeability of the lipoprotein membrane that,
at low pH are capable of activating the zymogens (Schlines,
2007) [61]. Zymogen granules also contain trypsin inhibitors,
which are not active at the low pH present in lysosomes. If the
zymogen activation process proceeds vigorously, pancreatitis
can result with autodigestion of the pancreas. Activation of
intracellular enzymes results in cellular necrosis and
subsequent sterile inflammation, which leads to peri-
pancreatic fat necrosis (Bunch, 2003; Watson, 2004) [9, 76].
Neutrophil migration is initiated by Trypsin and chymotrypsin
into the pancreas, with the subsequent production of reactive
oxygen species and nitric oxide causing ongoing
inflammation (Keck et al., 2005) [37]. There is shift from
apoptosis to necrosis in pancreatitis, implicated by neutrophils
along with substances such as endothelin-1 and
phospholipase-A2 (PLA-2) (Windsor, 2000; Al-Mofleh,
2008) [86,1]. In the early course of Acute Pancreatitis,
Interleukin (IL)-8 is one of the major initiators of neutrophil
migration and also upregulates intercellular molecule
adhesion1 to promote adhesion of neutrophils to the
endothelial wall (Bhatia, 2000; Frossard, 1999) [6, 21].
Alteration in pancreatic circulation besides, stimulation of
multiple cytokines exacerbates inflammation (Cuthbertson,
2006; Makhija, 2002) [14, 47]. The serum and tissue anti-
proteases are consumed by the activated trypsin and other
protease enzymes resulting in the activation of the kinin,
coagulation, fibrinolytic and complement cascades leading to
systemic problems such as hemorrhage, shock, disseminated
intravascular coagulation (DIC) and vascular collapse (Bunch,
2003; Ettinger et al., 2005)[9, 16].
Signalment
Breed Predilection
Acute pancreatitis can affect any breed; however several
breeds are over represented like schnauzer, Yorkshire terrier,
spaniels, boxer, Shetland sheepdog and collies.
Age & Range
Typically affects middle-aged to older patients that may be
overweight or have history of dietary indiscretion.
Predisposing causes
Risk factors associated with development of acute
pancreatitis in dogs.
Risk factors are given in Table 1. (Adapted from: 1. Cook et
al., 1993 [13]; 2. Hess et al., 1998 [27]; 3. Bunch, 2003 [9]; 4.
Watson, 2004 [76]; 5. Hill and Van Winkle, 1993 [29]; 6. Ferreri
et al., 2003 [18]; 7. Mix and Jones, 2006 [52]; 8. Simpson,
2001b [63]; 9. Washabau, 2001 [75]; 10. Simpson and Lamb,
1995 [63]; 11. Weiss et al., 1996 [81]; 12. Akol et.al., 1993[2] ;
13. Gaskill and Gribb, 2000 [23].
Causes
Causes of pancreatitis include
Intrinsic factors such as biliary disease, hypertriglyceridemia,
gastric/duodenal disease, and primary pancreatic disease –
tumor, cyst.
Extrinsic factors include diet (high fat), drugs/toxins, and
surgical manipulation. Direct effects could include direct
toxicity or hypersenstivity reaction. Indirect effects could
~511~
The Pharma Innovation Journal
include ischemia, thrombosis, and increased viscosity of
pancreatic fluid. Many drugs can potentially cause
pancreatitis, but a few are more commonly associated with the
disease. These drugs include seizure medications, such as
potassium bromide; chemotherapy drugs such as vinblastine,
cisplatin, L-asparaginase and azathioprine; and antibiotics,
such as tetracycline and the sulfonamides, steroids (only in
association with intervertebral disc disease and surgery),
propofol, thiazide diuretics, procainamide, organophosphates,
cholinergic agonists Trimethoprim, sulfamethoxazole has
been thought to cause an immune mediated pancreatitis in
dogs (Schlines, 2007, Dalefield et al., 1999; Trepanier et al.,
2003) [61, 15, 72].
Clinical picture
Dogs with Acute pancreatitis generally present with a sudden
onset of anorexia, depression, vomiting (which can be either
self limiting ceasing within 12-24 hours or life threatening
depending upon the severity of the disease), abdominal pain,
sometimes fever and diarrhea (Hess et al., 1998) [27]. Affected
dogs attain “praying position” or “position of relief” in
response to cranial abdominal pain (Bunch, 2003) [9]. There
are signs of dehydration and shock such as tachycardia,
tachypnea, prolonged capillary refill time, hypothermia, and
dry mucous membranes. Acute renal failure may develop
secondary to hypovolemia and ischemia resulting from
vomiting as well as potential development of intravascular
coagulopathy and direct inflammation (Zhang et al., 2008)[87].
Aggregation of activated neutrophils in the glomeruli is
caused due to activation of nuclear factor kappa B (Satoh et
al., 2003) [58]. Acute lung injury also may develop in dogs, the
pathogenesis of which is linked to platelet activating factor,
although PLA-2, tumor necrosis factor alpha (TNF-α), and
IL-1 may also play a role (Lopez et al., 1995, Gomez-
Cambronero et al., 2002) [45, 25]. Other systemic complications
include disseminated intravascular coagulation and cardiac
arrhythmias, mediated by the many systemic inflammatory
cascades. Diabetic ketoacidosis is a commonly reported
comorbidity in canine with Acute pancreatitis (Lem et al.,
2008) [44], causing trypsin activation and acinar cell necrosis,
rather than the exocrine inflammation destroying the acinar
cells (Bhoomgoud et al., 2009) [7]. Late-onset complications
such as chronic relapsing pancreatitis and the subsequent
development of exocrine pancreatic insufficiency or diabetes
mellitus have been described in dogs (Watson, 2003; Watson
et al., 2010) [77, 78].
Histological Scoring Of Pancreatitis
A follow-up study by Newman et al. (2006) [53] suggested a
histological grading system for canine pancreatitis in which a
number of histological features were graded on each
histological section between 0 and 3 where grade 0=none of
the section affected; grade 1 was up to 10% of the section
affected; grade 2 was 10–40% of the section affected and
grade 3 was over 40% of the section affected. The histological
features graded were: neutrophilic inflammation; lymphocytic
inflammation; pancreatic necrosis; fat necrosis; oedema;
fibrosis; atrophy and nodules. This grading system has
subsequently been used by others in canine studies (Watson et
al. 2011; Bostrom et al., 2013) [79, 8] but has yet to be
extensively validated by independent pathologists.
Mortality Rates
The reported mortality rate for AP in dogs ranges from 27%
to 58% (Charles, 2007; Cook.et al., 1993; Ruaux, 1998) [11, 13,
57].
Diagnosis
Haematological findings
Complete blood cell count should be conducted on all the
patients. Peripheral blood neutrophilia with a degenerative left
shift and leucocytosis is common; anemia and
thrombocytopenia are the early indications of disseminated
intravascular coagulation. An elevated packed cell volume
may be observed secondary to hemoconcentration (Steiner,
2003; Hess et al., 1998) [65, 27].
Serum Biochemistry
Azotemia: Azotemia is often present in dogs with acute
pancreatitis which may be pre-renal or renal in origin (Hill et
al., 1993; Hess et al.,1998; Gerhardt et al., 2001; Bunch,
2003) [29, 24, 9]. Prerenal azotemia develops as a result of
dehydration and renal azotemia may occur secondary to
hypovolemia or shock or may be associated with multiorgan
dysfunction. If fluid therapy doesn’t resolve it, then there is
possibility of renal failure (Williams, 2000) [82].
Hyperbilirubinemia: Hyperbilirubinemia (two-fold to five-
fold increase), present in 30-53% of dogs noticed in cases of
cholestasis (Hill et al., 1993; Hess et al., 1998; Gerhardt et
al., 2001; Washabau, 2001) [29, 27, 24, 75] which develops
secondary either to pancreatic inflammation or to fibrosis,
which obstructs (partially or completely) the common bile
duct (Bunch, 2003; Watson, 2004; Mix et al.,2006) [9, 76, 52].
Elevated Hepatic enzymes: Hepatic ischemia, local
inflammatory mediators and toxic pancreatic mediators in the
portal circulation lead to hepatocellular injury with increased
liver enzymes in dogs (ALT, ALKP and AST) (Hill et al.,
1993; Hess et al., 1998) [29, 27]. Alkaline phosphatase (ALKP)
may be two to 15 times normal and alanine aminotransferase
(ALT) may be two to five times normal. Cholestasis can also
result in increased AST, ALT and alkaline phosphatase (AP)
(Watson, 2004) [76].
Hyperglycemia and hypoglycemia: Hyperglycemia develops
due to glucagon release in excess of insulin from an inflamed
pancreas, in combination with stress-related increases of
cortisol and catecholamines (Hill et al., 1993; Bunch, 2003;
Watson, 2004) [29, 9, 76]. Concurrent diabetes mellitus or keto-
acidosis or the development of diabetes after acute episodes
of pancreatitis is another possible explanation for the detected
hyperglycemia (Watson, 2004) [76]. More severe cases of
acute pancreatitis are usually characterized by hypoglycemia
(39%) (Hess et al., 2000)[28].
Hypocalcaemia: Mild to moderate hypocalcaemia has also
been reported in dogs with pancreatitis. Hypocalcaemia is
thought to occur as a result of deposition of calcium (such as
soaps in peri-pancreatic fat) within the pancrease, which
occurs secondary to pancreatic inflammation, an acute shift of
calcium in soft tissues, and hormonal imbalances (e.g.
thyrocalcitonine and abnormal parathyroid responsiveness)
are possible factors (Bunch, 2003; Watson, 2004; Mix et al.,
2006) [9, 76, 52]. However hypocalcaemia is rarely severe
enough to result in clinical signs related to low serum calcium
(Williams, 1996) [83].
Hypercholesterolemia: is also commonly identified in dogs
with Acute pancreatitis (Mix et al., 2006) [52].
Hyperlipemia: Hyperlipemia can be either a cause or, more
likely as a result of the disease (Watson, 2004) [76]. In
addition, hyperlipemia can be associated with other diseases,
~512~
The Pharma Innovation Journal
such as endocrinopathies and hepatic lipidosis, that can
concurrently affect both dogs and cats with pancreatitis (Hill
et al., 1993; Mansfield et al., 2001) [29, 48].
Hypoalbuminemia: Hypoalbuminaemia may be a
consequence of systemic inflammation. Albumin may also be
lost from leaky blood vessels into the extracellular space and
into ‘third spaces’ (e.g., peritoneal cavity, pleural cavity) as a
result of pancreatitis-induced vasculitis.
Hyperproteinemia: occurs secondary to dehydration (Bunch,
2003, Mix et al., 2006) [9, 52].
Electrolyte abnormalities: Vomiting and reduced food intake
can lead to hyponatremia, hypochloremia and hypokalemia
(Watson, 2004). In dogs, hypochloremia is the most frequent
electrolyte abnormality (81.3%), while hypokalemia is more
common in cats (56%) (Hill et al., 1993; Hess et al., 1998) [27,
29].
Hyperamylasemia and hyperlipasemia: Traditionally Serum
amylase and lipase were used for diagnosing acute
pancreatitis in companion animals but because of both
pancreatic and extrapancreatic sources, they have poor
specificity. Reported sensitivities of these enzymes for a
diagnosis of pancreatitis are 50% to 70% (Mix et al., 2006)
[52].
Diagnostic imaging
The most commonly used imaging techniques for assessing
the pancreas in veterinary patients are abdominal radiography
and ultrasonography (Mix et al., 2006) [52].
Radiography
Radiographic findings in dogs with pancreatitis are subjective
and include loss of detail in the cranial abdomen,
displacement of the stomach to the left, and displacement of
the duodenum to the right or ventrally, widened pyloric-
duodenal angle. The colon may be displaced caudally in some
patients (Steiner, 2003; Mahafey et al., 1998; Holm et al.,
2003) [70, 46, 30]. In a retrospective study of fatal cases of canine
pancreatitis, only 24% of dogs had radiographic abnormalities
attributable to pancreatitis (Hess et al., 1998) [27]. Therefore,
abdominal radiography has a low sensitivity in diagnosing
pancreatitis (Raux, 2003) [56]. Abdominal radiography is still a
very important part of the diagnostic workup for a dog with
acute onset of vomiting or abdominal pain. This is mainly
because of the ability to rule in or rule out intestinal
obstruction or other changes such as free gas within the
abdomen or a distended, fluid-filled uterus. Abdominal
radiography is widely available, safe, noninvasive, and
relatively inexpensive. Images may be evaluated immediately,
which is important in critically ill patients.
Ultrasonography
Ultrasonography is more sensitive than radiography in
diagnosing pancreatitis. Sensitivity and specificity of
abdominal ultrasonography has been shown to be highly
operator-dependent and sensitivity has been reported to be up
to 68% in dogs (Hess, 1998) [27]. Changes in pancreatic
echogenicity and development of focal lesions (Nyland, 1983;
Lamb, 1995) [54, 38] due to pancreatic edema, necrosis, or
hemorrhage secondary to pancreatitis can be detected. Acute
necrotizing pancreatitis is frequently associated with an
enlarged, hypoechoic pancreas and peripancreatic necrosis
(manifested as hyperechogenicity surrounding the pancreas)
and fluid accumulation around the pancreas (Mix et al., 2006)
[52]. Complications of pancreatitis, such as pancreatic
abscesses or pseudocysts, may also be identified via
ultrasonography. Extrahepatic biliary obstruction should be
ruled out during an abdominal ultrasound (Schlines, 2007) [61].
Computed tomography
CT is the most widely used diagnostic test in assessing
pancreatitis in humans and is considered to be the most
effective method of detecting inflammatory disease of the
pancreas (Haaga et al., 1977) [26]. However, limited
information is available regarding the value of CT in
veterinary patients. Peripancreatic changes, including the
presence of peripancreatic fluid and thickening of tissue in the
pancreatic regions, may also be noted. A major concern with
the use of CT in diagnosing pancreatitis in dogs is the
requirement of anesthesia to obtain images. Even in sedated
or moribund patients, motion artifact interferes with accurate
CT of the pancreas (Mix et al., 2005) [51]. The suitability of an
individual patient for anesthesia must be assessed before
pursuing abdominal CT. The availability of CT is limited and
may be financially prohibitive for some owners.
Biopsy
Biopsy of the pancreas remains the gold standard in
diagnosing canine acute pancreatitis (Steiner, 2003) [65]. It is
highly specific, but the sensitivity of pancreatic biopsy is poor
because pancreatitis may be localized to small regions within
the pancreas. Pancreatic biopsy may be performed via
surgically (laparoscopy or laparotomy) or ultrasound guided
fine needle aspiration (Schlines, 2007) [61]. Visual inspection
of the pancreas may confirm suspected pancreatitis. However,
a normal gross appearance of the pancreas does not exclude
the possibility of microscopic pancreatic inflammation and
clinically significant pancreatitis (Steiner, 2003) [70].
Laparoscopic evaluation of the pancreas is less invasive than
laparotomy. Ultrasound-guided fine-needle aspiration of the
pancreas may be performed without anesthesia and may
reveal inflammation, necrosis, or sepsis of the pancreas
(Center, 2004) [10]. Because of the regional nature of
pancreatitis, normal results of fine-needle aspiration cannot
exclude a diagnosis of pancreatitis. Therefore, fine needle
aspiration of the pancreas is a relatively specific, but not
sensitive, diagnostic test for pancreatitis.
Diagnostic Markers
Trypsinogen activation peptide
During the inappropriate activation of trypsinogen to trypsin,
TAP is released into the Pancrease where it may diffuse into
the intravascular or peritoneal space. Trypsin activation
peptide (TAP) may be measured in the serum or urine of
patients clinically suspected of having pancreatitis. A
significant increase can be seen during the first hours after the
development of pancreatitis, especially in the more severe
necrotizing forms. For less severe forms, the usefulness is
thus limited (Ruaux, 2003) [56]. Because the onset of the
disease is not known in veterinary patients, it is possible that
the concentration of TAP is already decreasing at the time of
measurement (Ruaux, 2003) [56], which could explain the
rather low sensitivity. It is considerably more sensitive and
specific in assessing the severity than canine trypsin like
immunoreactivity (cTLI) (Mansfield et al., 2003), but its
lability and limited availability limit its usefulness (Williams,
2000) [82].
Serum canine trypsin like immunoreactivity (cTLI)
Serum canine trypsin-like immunoreactivity (cTLI) is a well-
known test for diagnosing exocrine pancreatic insufficiency in
~513~
The Pharma Innovation Journal
dogs, but it can also be used for acute pancreatitis. Early in
the disease, a rapid increase in cTLI can be detected (Bunch,
2003; Ruaux, 2003) [9, 56]. Elevations have a high level of
specificity, although decreased renal function can influence
this result (Simpson et al., 1995; Ruaux, 2003; Watson, 2004)
[63, 56, 76]. The sensitivity is rather low, because the period
during which cTLI is increased can be short due either to a
rapid down regulation of trypsinogen synthesis (especially in
severe cases, such as hemorrhagic necrosis of pancreatic
tissue) or to cleavage by endopeptidase. CTLI is a poor
predictor of outcome for acute pancreatitis (Mansfield et al.,
2003) [50]. Another limitation is that it does take several days
to run this test (Simpson et al., 1995; Mix et,al., 2006) [63, 52],
sensitivity of serum TLI concentration for the detection of
pancreatitis is limited to 30% to 60%, making serum cTLI
concentration a suboptimal diagnostic test for canine
pancreatitis(Steiner et al.,2001, Newman et al.,2004,
Mansfield et al.,2000) [68, 53, 48].
Serum canine pancreatic lipase immunoreactivity (cPLI)
The development of an enzyme-linked immunosorbant assay
and a radioimmunoassay for measuring serum canine
pancreatic lipase immunoreactivity (cPLI) is an important
step in diagnosing acute pancreatitis in dogs (Steiner et al.,
2000; Steiner et al., 2001c) [67, 69] and developed by Texas A
& M researchers. It can be considered the single best blood
test because of its high specificity and sensitivity (Steiner et
al., 2001a) [66]. The high specificity results from the fact that
canine pancreatic lipase is only expressed by pancreatic acinar
cells, without cross-immunoreactivity with other lipases or
related proteins expressed by other tissues such as the
stomach and salivary glands, as pancreatic lipase is
antigenically unique compared with lipase produced in other
parts of the body and cannot be measured with this test.
(Steiner et al., 2000) [67]. Furthermore, renal failure and
administration of steroids do not seem to contribute to
elevated levels of cPLI (Steiner et al., 2001b; Watson, 2004)
[68, 76]. The reference range for serum cPLI is reportedly 2.2–
102 µg/L. Using a cut-off value of 200µg/L, the test was 82%
sensitive and 100% specific (Richard). The major drawback
of this test is that results are generally not available for
several days because of the limited availability of the test.
This delay in results is problematic, particularly in critically
ill patients. The current commercially available test for
specific canine pancreatic lipase (Spec-cPL) is a sandwich
enzyme linked immunosorbent assay, using a recombinant
peptide as the antigen and monoclonal antibody. Using Spec-
cPL, results ≤ 200 µg/L are expected in healthy dogs, and
results >400µg/L are considered consistent with a diagnosis
of pancreatitis (Huth et al., 2010) [35]. An in-clinic rapid
semiquantitative assay (SNAP-cPL, Idexx, Maine, USA) has
also been developed and shows good alignment and
reproducibility with Spec-cPL (Beall et al., 2011) [3]. Spec-
cPL has a sensitivity of 63.6%. The sensitivity of cPLI and
Spec-cPL increased with increasing severity of pancreatic
inflammation.
C Reactive protein
Because acute pancreatitis is an inflammatory process, acute-
phase response proteins such as C-reactive protein (CRP) are
released by the liver. In human medicine, the measurement of
this protein constitutes an effective tool for assessing the
severity of the disease, with more severe cases showing
higher levels of CRP (Mix et al., 2006) [52]. Acute pancreatitis
is one of the diseases with the highest CRP levels. However,
because CRP can be released secondary to any type of
inflammation, infection, tissue damage or trauma, the
specificity is too low to play a role in diagnosing acute
pancreatitis (Spillman et al., 2002) [64]. Measurement of CRP
concentrations can however aid in assessing the severity of
the disease (Holm et al., 2004) [31]. A study in dogs with
pancreatitis has shown elevated levels of CRP in dogs with
pancreatic necrosis compared with dogs with edematous
pancreatitis (Spillman, 2002) [64]. A more practical application
of this test, rather than the diagnosis of pancreatitis, may be as
a tool to monitor the progression or resolution of pancreatitis
or as a prognostic indicator.
Urinalysis
Urinary TAP is considered even less accurate than serum
TAP in diagnosing severe pancreatitis, because it is not
significantly different between healthy dogs, dogs with
pancreatitis and dogs with non-pancreatic disease (Mansfield
et al., 2000a; Mansfield et al., 2003) [48, 50]. However, in the
study by (Mansfield et al., 2000a) [48] dogs that died of severe
pancreatitis did have higher urinary TAP than dogs with
milder forms.
Treatment
Intravenous fluid therapy
Vomiting and inappetance result in dehydration in dogs with
AP, which generally requires IV fluid replacement. In
addition to the systemic effects of dehydration or
hypovolaemia, the pancreas is very sensitive to altered blood
flow. Disturbed pancreatic microcirculation is usually multi-
factorial in origin and can occur as a result of increased
vascular permeability resulting from inflammatory cytokines,
and microthrombi formation resulting from
hypercoagulability (Gardner et al., 2008) [22]. There is a
theoretical benefit in using alkalinising fluids, such as lactated
ringer’s solution (LRS), to increase pH and therefore prevent
further trypsin activation within the acinar cell (Bhoomagoud
et al., 2009) [7]. There is no current recommended preference
for either the use of LRS or saline solution as the initial
crystalloid of choice. There are multiple rodent experimental
studies that show a beneficial effect of dextrans over
crystalloid therapy in Acute pancreatitis (Hotz et al., 1996,
Huch et al., 1995) [33, 34].
Plasma
Purpoted benefits of Plasma transfusion (6-12ml/kg) in
treatment of AP include replacement of circulating α-
macroglobulins, coagulation factors and anti-inflammatory
factors (Weatherton et al., 2009) [80]. Administration of
plasma was shown to be superior to both crystalloid and
colloid administration in a rat experimental model of
pancreatitis (Leese et al., 1998) [42]. Fresh frozen plasma
(FFP) contains the anti-proteases that may help neutralize
enzymes. FFP also has anti inflammatory proteins such as
albumin which could be beneficial. Fresh frozen plasma
(FFP) has only about 20-30% of the oncotic properties of
colloids (Weatherton et al., 2009) [80]. Despite an
experimental benefit of FFP in rats (Leese et al., 1988) [42],
there has been no proven benefit in people (Leese et al. 1991,
Leese et al. 1987) [40, 41] or in dogs (Weatherton et al., 2009)
[80] and it remains an expensive treatment for veterinary
patients. In the light of these findings, administration of FFP
should probably be reserved for those dogs with documented
~514~
The Pharma Innovation Journal
coagulation abnormalities.
Analgesia
Pain is a common clinical sign of acute pancreatitis, and is
manifested in dogs typically with a crouched appearance
(Hess et al., 1998) [27]. Pain is likely to be mediated due to
local effects- whereby the inflamed and enlarged pancreas
itself causes pain, or by subsequent amplification of visceral
pain. A number of amino acids (glutamate and aspartate) and
neuropeptides (substance P, neurokinin A, calcitonin gene-
related peptide) are involved in a complex circuit of pain
recognition and transmission (Mansfield, 2003) [50].
Multidimensional scales published for use in dogs that
consider aspects other than pain intensity include the
Melbourne Pain Scale (Firth et al.,1999) [19] and the Glasgow
Composite Pain Scale (GCPS) (Holton et al., 2001) [32] as in
Table 2.
Nutrition
If the enterocytes doesn’t get the luminal nutrients and
aminoacids then gastrointestinal tract is thought to be the
main contributor of systemic inflammatory state during acute
pancreatitis, which is a catabolic disease causing significant
nitrogen loses increases nutritional requirements particularly
due to pancreatic necrosis (Flint et al., 2003) [20].
Anti emetics
In dogs affected with AP, vomiting is both centrally and
peripherally mediated. Maropitant, an effective anti emetic
agent blocks both centrally and peripherally mediated emesis
by blocking Neurokinin1 (NK1) receptor and substance P
production (Karanjia, 1990; Conder, 2008; Rau et al., 2010;
Benchaoui, 2007; Sedlacek et al.,2008; Victor 2007; ) [36, 12, 4,
62, 74, 55].
Gastric acid reduction
Proton pump inhibitors are the preferable agents to increase
the gastric Ph for gastric mucosal health by preventing the
development of gastric mucosal ulcerations, also increased
gastric Ph decreases exocrine pancreatic stimulation (Leffler,
2009; Bersens et al., 2005) [43, 5].
Table 1: Risk factors of acute pancreatitis in dogs
Hyperlipidemia Inherent abnormal lipid metabolism (Miniature schnauzers) 4, 9, 11, accumulation of toxic fatty acids in
the pancreas1, ingestion of a large fatty meal3, concurrent disease 2, 4, 13
Concurrent diseases Diabetes mellitus 13, hypercortisolism 13, Hypothyroidism 2, 4
Infection /infestation Viral, parasitic, mycoplasmal, bacterial, protozoa (Toxoplasma gondi, Babesia canis ),hepatic flukes.
Other causes Uremic pancreatitis1, prior gastrointestinal disease 2, hypercalcaemia 4,11 and thrombus formation 2
Table 2: Catagories of Pain intensity.
Mild to
Moderate
Quiet but responsive to surroundings Unsettled
Looks around when abdomen is palpated
Buprenorphine with or without
Lidocaine and/or Ketamine infusion.
Moderate to
Severe
Decreased response to surroundings or stimuli Slow or reluctant to move Restless
Stretching of abdomen, looking around at abdomen Flinches on abdominal palpation
Buprenorphine with Lidocaine and
Ketamine infusion.
Severe to
excruciating
Non responsive to stimuli refuses to move or getup screams, cries or snaps when
tries to get up or when abdomen palpated.
Epidural morphine with
lidocaine/ketamine infusion.
Conclusion
Because of the unspecific clinical symptoms, AP is an
underestimated disease in canines resulting in severe
morbidity or death in patients. The combined interpretation of
history, clinical signs, various biochemical, serological tests
and imaging techniques can be effective for confirmation of
the disease. For evaluating the complications of AP and
assessing the general condition of the patient, complete blood
count, serum biochemistry and urinalysis are preferred and for
definitive diagnosis other laboratory tests must be used,
because of the high sensitivity and specificity, pancreatic
lipase immunoreactivity (PLI) is currently the most reliable
test in both canine and feline. Thus by the collective
interpretation of various tests, most of the cases can be readily
diagnosed for initiating a rapid corrective therapy.
References
1. Al Mofleh IA. Severe acute pancreatitis: pathogenetic
aspects and prognostic factors. World J Gastroenteroly.
2008; 14:675-684.
2. Akol KG, Washabau RJ, Saunders HM, Hendrick MJ.
Acute pancreatitis in cats with hepatic lipidosis. J Vet Int
Med. 1993; 7:205-209.
3. Beall MJ, Cahill R, Pigeon K et al. Performance
validation and method comparison of an in-clinic
enzyme-linked immunosorbent assay for the detection of
canine pancreatic lipase. J Vet Diagn Invest. 2011;
23:115-119.
4. Benchaoui HA. Efficacy of maropitant for preventing
vomiting associated with motion sickness in dogs.
Veterinary Record. 2007; 161:444.
5. Bersenas AM, Mathews KA, Allen DG et al. Effects of
ranitidine, famotidine, pantoprazole, and omeprazole on
intragastric pH in dogs. Am J Vet Res. 2005; 66:425-431.
6. Bhatia M, Brady M, Shokuhi S et al. Inflammatory
mediators in acute pancreatitis. J Pathol. 2000; 190:117-
125.
7. Bhoomagoud M, Jung T, Atladottir J et al. Reducing
Extracellular pH Sensitizes the Acinar Cell to
Secretagogue-Induced Pancreatitis Responses in Rats.
Gastoenterology. 2009; 137:1083-1092.
8. Bostrom BM, Xenoulis PG, Newman SJ et al. Chronic
pancreatitis in dogs: a retrospective study of clinical,
clinicopathological, and histopathological findings in 61
cases. The Veterinary Journal. 2013; 195:73-79.
9. Bunch SE. The exocrine pancreas. In: Nelson R.W.,
Couto C.G. (editors). Small Animal Internal Medicine.
Third edition, Mosby, St. Louis, Missouri, 2003, 552-560.
10. Center s. feline pancreatitis. Proc west vet conf proc,
2004.
11. Charles J. Pancreas, in Maxie MG (ed): Jubb, Kennedy,
and Palmer’s Pathology of Domestic Animals 5th ed.
Edinburgh, Saunders Elsevier, 2007, 389-423.
12. Conder GA. Efficacy and safety of maropitant, a selective
~515~
The Pharma Innovation Journal
neurokinin1 receptor antagonist, in two randomized
clinical trials for prevention of vomiting due to motion
sickness in dogs. Jof vet pharm and therapeutics. 2008;
31:528.
13. Cook AK, Breitschwerdt EB, Levine JF et al. Risk
factors associated with acute pancreatitis in dogs: 101
cases (1985-1990). J Am Vet Med Assoc. 1993; 203:673-
679.
14. Cuthbertson CM, Christophi C. Disturbances of the
microcirculation in acute pancreatitis. Br J Surg. 2006;
93:518-530.
15. Dalefield R, Fickbohm B, Oehme FW. Possible
therapeutic effect of chlorpromazine on canine
pancreatitis resulting from organophosphate toxicosis. N
Z Vet. J. 1999; 47:75-76.
16. Ettinger SJ, Feldman EC, eds. Textbook of internal
vety.medicine diseases of dog and cat 6th ed Philadelphia,
Pa; WB Saunders Co. 2005, 1482-1488.
17. Evans HE. Miller’s Anatomy of the Dog. W. B. Saunders
Company, Philadelphia, PA, USA. 1993.
18. Ferreri JA, Hardam E, Kimmel SE, Saunders HM, Van
Winkle TJ, Drobatz KJ et al. Clinical differentiation of
acute necrotizing from chronic nonsuppurative
pancreatitis in cats: 63 cases (1996-2001). J Ame Vet
Med Association. 2003; 223:469-474.
19. Firth AM, Haldane SL. Development of a scale to
evaluate postoperative pain in dogs. J Am Vet Med
Assoc, 1999; 214:651-659.
20. Flint RS, Windsor JA. The role of the intestine in the
pathophysiology and management of severe acute
pancreatitis. World Journal of Gastroenterology. 2003;
5:69-85.
21. Frossard JL, Saluja A, Bhagat L et al. The role of
intercellular adhesion molecule 1 and neutrophils in acute
pancreatitis and pancreatitis-associated lung injury.
Gastroenterology. 1999; 116:694-701.
22. Gardner TB, Vege SS, Pearson RK et al. Fluid
Resuscitation in Acute Pancreatitis. Clinical
gastroenterology and hepatology: the official clinical
practice. J of the Ame Gastroenterological Assoc. 2008;
6:1070-1076.
23. Gaskill CL, Cribb AE. Pancreatitis associated with
potassium bromide / phenobarbital combination therapy
in epileptic dogs. Can Vet J. 2000; 41:555-558.
24. Gerhardt A, Steiner JM, Williams DA, Kramer S, Fuchs
C, Janthur M et al. Comparison of the sensitivity of
different diagnostic tests for pancreatitis in cats. J of Vet
Internal Med. 2001; 15:329-333.
25. Gomez-Cambronero LG, Sabater L, Pereda J et al. Role
of cytokines and oxidative stress in the pathophysiology
of acute pancreatitis: therapeutical implications. Curr
Drug Targets Inflamm Allergy. 2002; 1:393-403.
26. Haaga JR, Alfidi RJ, Havrilla TR et al. Definitive role of
ct scanning of the pancreas. Radiology. 1977; 124:723-
730.
27. Hess RS, Saunders HM, Van Winkle TJ et al. Clinical,
clinicopathologic, radiographic, and ultrasonographic
abnormalities in dogs with fatal acute pancreatitis: 70
cases (1986-1995). J Am Vet Med Assoc. 1998a;
213:665-670.
28. Hess RS, Saunders HM, Van Winkle TJ et al. Concurrent
disorders in dogs with diabetes mellitus: 221 cases (1993-
1998). J Am Vet Med Assoc. 2000b; 217:1166-1173.
29. Hill RC, Van Winkle TJ. Acute necrotizing pancreatitis
and acute suppurative pancreatitis in the cat. J Vet Int
Med. 1993; 7: 25-33.
30. Holm J, Chan D, Rozanski E. Acute pancreatitis in dogs.
J Vet Emerg Crit Care. 2003; 13:201-213.
31. Holm J, Rozanski E, Freeman L et al. C-Reactive Protein
Concentrations In Canine Acute Pancreatitis. J Vet
Emerg Crit Care. 2004; 14:183-186.
32. Holton L, Reid J, Scott EM et al. Development of a
behaviour-based scale to measure acute pain in dogs. Vet
Rec. 2001; 148:525-531.
33. Hotz HG, Buhr H, Herfarth C et al. Benefits of various
dextrans after delayed therapy in necrotizing pancreatitis
of the rat. Intensive Care Med. 1996; 22:1207-1213.
34. Huch K, Schmidt J, Schratt W et al. Hyperoncotic
dextrans and systemic aprotinin in necrotizing rodent
pancreatitis. Sc and J Gastroenterol. 1995; 30:812-816.
35. Huth SP, Relford R, Steiner JM et al. Analytical
validation of an ELISA for measurement of canine
pancreas-specific lipase. Vet Clin Pathol. 2010; 39:346-
353.
36. Karanjia ND. Low dose dopamine protects against
hemorrhagic pancreatitis in cats. The Journal of surgical
research. 1990; 48:440.
37. Keck T, Friebe V, Warshaw AL et al. Pancreatic
proteases in serum induce leukocyte-endothelial adhesion
and pancreatic microcirculatory failure. Pancreatology.
2005; 5:241-250.
38. Lamb CR. Ultrasonographic findings in cholecystokinin-
induced pancreatitis in dogs. Vet Radiol. 1995; 36:27-32.
39. LaRusch J, Whitcomb DC. Genetics of pancreatitis.
Current Opinion in Gastroenterology. 2011; 27:467-474.
40. Leese T, Holliday M, Heath D et al. Multicentre clinical
trial of low volume fresh frozen plasma therapy in acute
pancreatitis. British Journal of Surgery. 1987; 74:907-
911.
41. Leese T, Thomas WM, Holliday M et al. A multicentre
controlled clinical trial of high-volume fresh frozen
plasma therapy in prognostically severe acute
pancreatitis. Annals of the Royal College of Surgeons of
England. 1991; 73:207-214.
42. Leese T, West K, Morton D et al. Fresh frozen plasma
therapy in acute pancreatitis: an experimental study.
International Journal of Gastrointestinal Cancer. 1988;
3:437-447.
43. Leffler A. Characterization of species-related differences
in the pharmacology of tachykinin NK receptors 1, 2 and
3. Biochemical pharmacology. 2009; 77:15-22.
44. Lem KY, Fosgate GT, Norby B et al. Associations
between dietary factors and pancreatitis in dogs. J Am
Vet Med Assoc. 2008; 233:1425-1431.
45. Lopez A, Lane IF, Hanna P. Adult respiratory distress
syndrome in a dog with necrotizing pancreatitis. Can Vet
J. 1995; 36:240-241.
46. Mahaffey M, Barber D. The peritoneal space, in thrall d
(ed): textbook of diagnostic veterinary radiology, ed 3.
philadelphia, wb Saunders, 1998, 441-457.
47. Makhija R, Kingsnorth AN. Cytokine storm in acute
pancreatitis. J Hepatobiliary Pancreat Surg. 2002; 9:401-
410.
48. Mansfield CS, Jones BR. Plasma and urinary trypsinogen
activation peptide in healthy dogs, dogs with pancreatitis
and dogs with other systemic diseases. Australian
Veterinary Journal. 2000; 78:416-422.
49. Mansfield CS, Jones BR. Review of feline pancreatitis
~516~
The Pharma Innovation Journal
part two: clinical signs, diagnosis and treatment. J Feline
Med and Surg. 2001; 3:125-132.
50. Mansfield CS, Jones BR, Spillman T. Assessing the
severity of canine pancreatitis. Research in Vet Sci. 2003;
74:137-141.
51. Mix K, Fabiani M. unpublished data, evaluation of the
normal feline pancreas with computed tomography.
Houston, tx, gulf coast Veterinary specialists, 2005.
52. Mix K, Jones C. Diagnosing acute pancreatitis in dogs.
Compendium on Continuing Education for the Practicing
Veterinarian. 2006; 28:226-234.
53. Newman S, Steiner J, Woosley K et al. Localization of
pancreatic inflammation and necrosis in dogs. J Vet Int
Med. 2004; 18:488-493.
54. Nyland TG. Ultrasonic features of experimentally
induced, acute pancreatitis in the dog. Vet Radiol. 1983;
24:260-266.
55. Rau SE, Barber LG, Burgess KE. Efficacy of Maropitant
in the Prevention of Delayed Vomiting Associated with
Administration of Doxorubicin to Dogs. J Vet Int Med.
2010; 24:1452-1457.
56. Raux C. diagnostic approaches to acute pancreatitis. Clin
tech small anim pract. 2003; 18:245-249.
57. Ruaux C. General practice attitudes to the treatment of
spontaneous canine acute pancreatitis. Aust Vet Pract.
1998; 28:67-74.
58. Satoh A, Masamune A, Kimura K et al. Nuclear factor
kappa B expression in peripheral blood mononuclear
cells of patients with acute pancreatitis. Pancreas. 2003;
26:350-356.
59. Saunders HM. Ultrasonography of the pancreas. Prob in
Vet Med. 1991; 3:583-603.
60. Schaer M. A clinicopathologic survey of acute
pancreatitis in 30 dogs and 5 cats. J Am Anim Hosp
Assoc. 1979; 15:681.
61. Schlines T. Diagnosing canine pancreatitis. 2007, 24-34.
62. Sedlacek HS, Ramsey DS, Boucher JF et al. Comparative
efficacy of maropitant and selected drugs in preventing
emesis induced by centrally or peripherally acting
emetogens in dogs. J Vet Pharma and Therapeutics.
2008; 31:533-537.
63. Simpson K, Lamb C. Acute pancreatitis in the dog. In
Practice. 1995; 17:328-337.
64. Spillman T, Korrell J, Wittker A et al. Serum Canine
Pancreatic elastase and Canine c-reactive protein for the
diagnosis and prognosis Of acute pancreatitis in dogs.
Proc 12 ecvim-ca/esvim congress, 2002.
65. Steiner J. Diagnosis of pancreatitis. Vet clin small anim.
2003; 33:1181-1195.
66. Steiner JM, Broussard J, Mansfield CS, Gumminger SR,
Williams DA. Serum canine pancreatic lipase
immunoreactivity (cPLI) concentrations in dogs with
spontaneous pancreatitis. J Vet Int Med. 2001; 15:274.
67. Steiner JM, Williams DA. Development and validation of
a radioimmunoassay for the measurement of canine
pancreatic lipase immunoreactivity (cPLI) in serum. J Vet
Int Med. 2000a; 14:378.
68. Steiner JM, Finco DR, Gumminger SR, Williams DA.
Serum canine pancreatic lipase immunoreactivity (cPLI)
in dogs with experimentally induced chronic renal failure.
Jl of Vet Int Med. 2001b; 15:311.
69. Steiner JM, Gumminger SR, Williams DA. Development
and validation of an enzyme-linked immunosorbent assay
(ELISA) for the measurement of canine pancreatic lipase
immunoreactivity (cPLI) in serum. J Vet Int Med. 2001c;
15:311.
70. Steiner JM. Diagnosis of pancreatitis. Veterinary Clinics
of Small Animals. 2003a; 33:1181-1195.
71. Szabo A, Sahin-Toth M. Increased activation of
hereditary pancreatitis associated human cationic
trypsinogen mutants in presence of chymotrypsin c. J
Biol Chem. 2012; 287:20701-20710.
72. Trepanier LA, Danhof R, Toll J, Watrous D. Clinical
findings in 40 dogs with hypersensitivity associated with
administration of potentiated sulfonamides. J Vet Intern
Med. 2003; 17:647-652.
73. Van Den Bossche I, Paepe DS, Daminet. Acute
pancreatitis in dogs and cats pathogenesis, clinical signs
and clinicopathologic findings. 2010; 79:13-22.
74. Victor A. Efficacy of maropitant for treatment and
prevention of emesis caused by intravenous infusion of
cisplatin in dogs. Amer J Vet Res. 2007; 68:48.
75. Washabau RJ. Feline acute pancreatitis-important species
differences. J Feline Med and Surg. 2001; 3:95-98.
76. Watson P. Pancreatitis in the dog: dealing with a
spectrum of disease. In Practice. 2004; 26:64-77.
77. Watson PJ. Exocrine pancreatic insufficiency as an end
stage of pancreatitis in four dogs. J Small Anim Pract.
2003; 44:306-312.
78. Watson PJ, Archer J, Roulois AJ et al. Observational
study of 14 cases of chronic pancreatitis in dogs. Vet
Rec. 2010; 167:968-976.
79. Watson PJ, Roulois A, Scase T et al. Characterization of
chronic pancreatitis in English Cocker Spaniels. J of Vet
Int Med. 2011; 25:797-804.
80. Weatherton LK, Streeter EM. Evaluation of fresh frozen
plasma administration in dogs with pancreatitis: 77 cases
(1995-2005). J Vet Emerg Crit Care (San Antonio). 2009;
19:617-622.
81. Weiss DJ, Gagne JM, Armstrong PJ. Relationship
between inflammatory hepatic disease and inflammatory
bowel disease, pancreatitis, and nephritis. J the Amer Vet
Med Assoc. 1996; 20:1114-1116.
82. Williams D. exocrine pancreatic disease, in Ettinger S,
Feldman E (eds): textbook of veterinary internal
medicine. Philadelphia, wb Saunders, 2000, 1345-1367.
83. Williams D. The pancreas, in guilford WG, center SA,
Strombeck DR, et al (eds): small animal
gastroenterology, ed 3. Philadelphia, wb Saunders, 1996,
381-410.
84. Williams DA. Exocrine pancreatic disease. In: Ettinger
S.J., Feldman E.C. (editors). Textbook of Veterinary
Internal Medicine: Diseases of the dog and cat. Fifth
edition, W.B. Saunders Company, Philadelphia, 2000,
1345-1355.
85. Windsor JA, Fearon KC, Ross JA et al. Role of serum
endotoxin and antiendotoxin core antibody levels in
predicting the development of multiple organ failure in
acute pancreatitis. Br J Surg. 1993; 80:1042-1046.
86. Windsor JA, Hammodat H. Metabolic management of
severe acute pancreatitis. World J Surg. 2000; 24:644-
672.
87. Zhang XP, Wang L, Zhou YF. The Pathogenic
mechanism of severe acute pancreatitis complicated with
renal injury: a review of current knowledge. Dig Dis Sci.
2008; 53:297-306.
