Title

Subtitle

pancreatitis (from TAMU Gastrointestinal lab)

Gastrointestinal Laboratory
Dr. Jörg M. Steiner
Department of Small Animal Clinical Sciences
Texas A&M University, 4474 TAMU
College Station, TX 77843-4474

 

Current Website Link: http://vetmed.tamu.edu/gilab/research/pancreatitis-information 

 

Pancreatitis Information

Introduction

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 picture

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 with pancreatitis.

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.

Diagnostic imaging

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 clinically useful.

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 modalities.

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)

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.

Pancreatic lipase immunoreactivity (PLI)

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.

Pancreatic biopsy

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

References

  1. Newman SJ, Steiner JM, Woosley K, et al. Localization of histologic pancreatitis lesions in dogs. J Vet Int Med 2004; 18:488-493.
  2. 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.
  3. 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 2001;15:274 (abstract).
  4. 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 (abstract).
 
Pancreatitis support group

Pancreatitis Update

www.IVIS.org

UPDATE ON PANCREATITIS IN DOGS
Kenneth W Simpson BVM&S,
PhD, MRCVS, DipACVIM,
DipECVIM
College of Veterinary Medicine
Cornell University

[email protected]

From a clinical perspective pancreatitis can be
broadly categorized as acute, recurrent acute or
chronic. It can be further classifi ed according to
its effect on the patient as mild or severe, nonfatal
or fatal, and also by the presence of sequela
such as abscess formation. Histologically, acute
pancreatitis is characterized by fi ndings that
range from pancreatic edema to necrosis, variable
infi ltrates of mononuclear and polymorphonuclear
cells, and local changes such as peri-pancreatic
fat necrosis and thrombosis. Acute pancreatitis
may resolve or persist and can be complicated
by secondary infection and pseudocyst or abscess
formation. It is tempting to equate mild acute
pancreatitis with pancreatic edema, and severe
or fatal pancreatitis with pancreatic necrosis, butthis relationship has not been critically examined
in patients with naturally occurring pancreatitis.
Chronic pancreatitis is characterized by fi brosis
and low grade mononuclear infl ammation and
may be a sequela of recurrent acute pancreatitis
or a subclinical disease process that may present
as diabetes mellitus or exocrine pancreatic
insuffi ciency (EPI).

Etiology and Pathogenenesis
The etiology and pathogenesis of spontaneous
pancreatitis is poorly understood. The major
factors which have been implicated (by
association) as causes of acute pancreatitis in the
dog and the experimental evidence to support
their involvement are summarized as follows:


 

 

Potential Aetiology          Clinical                    Experimental

 Hyperlipidemia                               Lipemia                              High fat diet
                                                   Abnormal lipid profiles           IV Free Fatty Acids
                                                   Lipodystrophy
 Diet                                             Diet indiscretion                  Fat >>protein diet
                                                   Obesity                              Ethionine supplementation
Bile reflux                                      Concomitant biliary               Bile infusion
                                                   disease (?cats)
Hypercalcemia                                Ca infusion                          Ca infusion
                                                   ? Hyperparathyroidism
Corticosteroids                               ? Hyperadrenocorticism         Increased CCK sensitivity
                                                   ? + Disc surgery?                 Pancreatic duct hyperplasia
Drug/toxin related                          Organophosphates              Organophosphates
                                                    L-asparaginase
                                                   Azathioprine, sulphonamides
                                                   Potassium bromide and Phenobarbital
                                                   Zinc
Ischemia/reperfusion                       Post-GDV                            Ex-vivo pancreas
Hereditary predisposition                 ? Miniature Schnauzer,
                                                   Min. poodle,Terriers,
                                                   non-sporting dogs
Endocrinopathies                           ? Hypothyroidism, diabetes mellitus

 

 

 Irrespective of the initiating cause pancreatitis
is generally believed to occur when digestive
enzymes are activated prematurely within the
pancreas. In the normal pancreas safeguards are
present to ensure that harmful pancreatic enzymes
are not activated until they reach the intestinal
lumen. Enzymes are stored in zymogen granules
within the acinar cell in the presence of pancreatic
secretory trypsin inhibitor (PSTI) and are released
at the apical surface directly into the duct system.

They are only activated in the intestine, by trypsin,
following the cleavage of trypsin activation
peptide (TAP) from trypsinogen by enterokinase.
Potential sites for the intrapancreatic activation
of pancreatic enzymes can therefore logically be
divided into interstitial (within the duct system
and interstitium) and intracellular (within the
acinar cell). Experimental studies suggest that
bile and enteric refl ux, and intravenous free fatty
acid (FFA) infusion initiate pancreatitis by an
interstitial mechanism whereas hyperstimulation
with caerulein or organophosphates, pancreatic
duct obstruction and choline defi cient ethionine
supplemented diet (CDE diet) result in
intracellular activation. Experimental pancreatic
hyperstimulation with cholecystokinin (CCK: or
its analogue cerulein), dietary supplementation
with ethionine, and obstruction of the pancreatic
duct lead to the formation of large intracellular
vacuoles in acinar cells. Vacuole formation is
thought to be a consequence of the uncoupling
of exocytosis of zymogens and abnormal
intracellular traffi cking of digestive and
lysosomal enzymes. These subcellular alterations
are considered to precipitate the intracellular
activation of digestive enzymes. Pancreatic
hyperstimulation may be of direct relevance to
naturally occurring pancreatitis in dogs. CCK is
normally released by cells in the duodenum in
response to intraluminal fat and amino acids and
coordinates and stimulates pancreatic secretion
and gallbladder contraction during digestion.

 It is possible that high fat diets exert their effects
via the excessive release of cholecystokinin
and that hypercalcemia, organophosphates and
high levels of circulating glucocorticoids also
facilitate (potentially by changing pancreatic
sensitivity to hyperstimulation), or cause
pancreatic hyperstimulation; however, this is
not proven. Edematous pancreatitis induced by
CCK hyperstimulation in dogs is characterized
by a rapid but self-limiting, burst of trypsinogen
activation suggesting that the pancreas has a
feedback mechanism to limiting trypsinogen
synthesis and activation (see nutritional
management). This concept of pancreatic
down regulation is important when considering
nutritional intervention in acute pancreatitis.Often pancreatic infl ammation is a self-limiting
process, but in some animals reduced pancreatic
blood fl ow and leukocyte and platelet migration
into the inflamed pancreas may cause progression to
pancreatic necrosis. Secondary infection may arise
by bacterial translocation from the intestine. Release
of active pancreatic enzymes and inflammatory
mediators from the infl amed pancreas, such as Tumor Necrosis Factor-α (TNF-α) interleukin-1 (IL-1) and phospholipid platelet activating factor
(PAF), amplifies the severity of pancreatic
inflammation, and adversely affects the function
of many organs (systemic inflammatory
response), and cause derangement in fl uid,
electrolyte and acid-base balance. It is the
development of multisystemic abnormalities
that separates mild from severe, potentially fatal pancreatitis.

 Diagnosis and Treatment
There is currently no single specific test for
pancreatitis in dogs and diagnosis is based
on a combination of compatible clinical,
clinicopathological and imaging findings.
Surgical biopsy may be required to confirm a
diagnosis, and to distinguish inflammation from
neoplasia.

Diagnostic approach and differential diagnosis
The differential diagnosis of acute pancreatitis
in dogs is usually centered round the problems
of vomiting and abdominal pain.
In vomiting dogs the initial approach is to
distinguish self-limiting from more severe
causes of vomiting on the basis of physical
fi ndings and a minimum database (e.g. Packed
cell volume, total protein, azostick, urinalysis,
plasma concentrations of sodium and potassium).
Where vomiting is associated with systemic

  Clinical findings
Signalment and History: Middle aged to old
dogs (>5yrs years old) who are overweight
appear at higher risk. Miniature Schnauzers,
Yorkshire and Silky Terriers, non-sporting
breeds and perhaps miniature poodles may be at
increased risk of developing pancreatitis. There
is no clear sex predisposition. Endocrinopathies
such as hypothyroidism, diabetes mellitus and
hyperadrenocorticism may also be risk factors.
Thirteen percent of 221 dogs with diabetes mellitus
had histological evidence of acute pancreatitis.
Hyperlipidemia is another potential risk factor.
The history may reveal a recent episode of
dietary indiscretion, toxin ingestion or drug
administration. Common clinical signs include
lethargy, anorexia, hunched stance, vomiting (±
blood), diarrhea (± blood), increased respiratory
rate and enlarged abdomen. Some dogs have a
history of icterus preceded by vomiting. Polyuria
and polydipsia may be present in dogs with
diabetes mellitus and pancreatitis.

Physical Examination:
Physical fi ndings in dogs with acute pancreatitis are variable and range from depression, to mild dehydration with signs of abdominal pain, to acute abdominal crisis with shock (tachycardia, prolonged capillary refill time, tacky mucous membranes, hypothermia), petechiation, icterus and ascites. An abdominal mass is palpated in some dogs.

 

 

Diagnostic approach and differential diagnosis
The differential diagnosis of acute pancreatitis
in dogs is usually centered round the problems
of vomiting and abdominal pain.
In vomiting dogs the initial approach is to
distinguish self-limiting from more severe
causes of vomiting on the basis of physical
fi ndings and a minimum database (e.g. Packed
cell volume, total protein, azostick, urinalysis,
plasma concentrations of sodium and potassium).
Where vomiting is associated with systemic
signs of illness, or is persistent, the clinician
has to differentiate metabolic, polysystemic
infectious, toxic and neurologic causes from
intra-abdominal causes. This is usually achieved
on the basis of combined historical and clinical
fi ndings coupled with a minimum database
and the evaluation of hematology and serum
chemistry profi le, urinalysis and abdominal
radiography. Measurement of serum amylase
or lipase is often reported on routine serum
chemistry profi le. Additional procedures such
as ultrasonography, abdominal paracentesis
or assay of trypsin-like immunoreactivity,
TAP or immunoreactive canine pancreatic
lipase are usually performed on the basis of
these initial test results and help to distinguish
pancreatitis from other intra-abdominal causes
of vomiting.
Where abdominal pain is the major fi nding
localizing abnormalities such as abdominal
distension are rapidly pursued with radiography,
ultrasonography and paracentesis while providing
supportive treatment on the basis of physical
fi ndings and a minimum data base and awaiting
the results of hematology, serum chemistry profi le
and urinalysis. Abdominal pain can arise from
any intra-abdominal structure. Musculoskeletal
disorders such as discospondylitis and prolapsed
discs can be hard to distinguish from abdominal
causes of pain.
Diarrhea, which was bloody in some cases, is
reported as a more frequent sign than vomiting in
dogs with experimental acute pancreatitis. Acute
pancreatitis and its complications (infection,
pseudocyst or abscess formation) should also
be considered in the differential diagnosis of
icterus and pyrexia. Some dogs with pancreatitis
exhibit few localizing clinical signs. Diagnosis in
these animals requires a high index of suspicion
and use of versatile diagnostic tests such as
ultrasonography. 

  Clinicopathological findings Hematology
Extremely variable, ranging
from mild neutrophilia and slightly increased
haematocrit, through marked leukocytosis with
or without a left shift, to thrombocytopenia,anemia and neutropenia with a degenerative left
shift. Thrombocytopenia in dogs with pancreatitis
is often associated with DIC and additional tests
of hemostasis (OSPT, APTT, FDP or D-dimer,
fi brinogen, antithrombin III) are performed to
determine if DIC or other coagulopathies are
present.

 Serum biochemistry
Serum biochemical
abnormalities include azotemia (pre-renal and
renal), increased liver enzymes (ALT, AST, AP),
hyperbilirubinemia, lipemia, hyperglycemia,
hypoproteinemia, hypocalcemia, metabolic
acidosis and variable abnormalities (usually
decreased) in sodium, potassium and chloride

Urinalysis
Enables azotemia to be characterized
as renal or pre-renal. Proteinuria occurs in some
dogs with acute pancreatitis and is usually
transient. The presence of glucose or ketonuria
should prompt consideration of diabetes
mellitus..

Pancreas specifc enzymes
Classically, elevations
in serum amylase and lipase activity have been
used as indicators of pancreatic infl ammation in
dogs. However these enzymes can be increased in
non-pancreatic disease, and dogs with confi rmed
pancreatitis may also have normal amylase
and lipase activity. For example, in dogs with
histologically confi rmed pancreatitis, lipase is
normal in 28 to 61% of dogs, and amylase is
normal in 31 to 47% of dogs. These limitations
have led to the development of assays for
enzymes or markers considered pancreatic in
origin such as trypsin-like immunoreactivity
(TLI), trypsinogen activation peptide (TAP),
and pancreatic lipase immunoreactivity (PLI).
Experimental studies have documented high
concentrations of TLI, TAP and PLI in dogs with
experimental acute pancreatitis. The utility of
TLI, TAP and PLI for the diagnosis spontaneous
pancreatitis in dogs has not been thoroughly
evaluated. Normal, subnormal and increased
concentrations of TLI have been observed in dogs
with confi rmed pancreatitis. Elevations of TAP
have been observed in the serum and urine (TAP:
creatinine) of dogs with severe pancreatitis, and
TAP may be a better prognostic than a diagnostic
indicator of pancreatic infl ammation. Experience
with PLI is even more limited, though it appears
more promising than TLI, as serum elevations of
PLI seem more substantial and prolonged than
TLI. Diseases such as renal disease can increase
TLI, TAP and PLI.

Radiography
Radiographic findings in dogs with
acute pancreatitis are generally non-specific and
include loss of serosal detail, increased opacity
in the right cranial quadrant of the abdomen,
displacement of the duodenum ventrally and/
or to the right, dilated hypomotile duodenum large intestine. Punctate calcification may
occasionally be identified in dogs with longstanding
pancreatitis; it indicates saponification
of mesenteric fat around the pancreas.
Thoracic radiographs may enable the detection of
pleural fl uid, edema or pneumonia which has been
associated with pancreatitis in dogs and cats.

Ultrasonography
Ultrasonographic fi ndingsinclude enlarged, hypoechoic pancreas, cavitary
lesions such as abscess or pseudocyst, dilated
pancreatic duct, swollen hypomotile duodenum,
biliary dilatation and peritoneal fl uid. One study
of dogs with fatal acute pancreatitis indicated that
ultrasound supported a diagnosis of pancreatitis
in 23/34 dogs. Disorders other than pancreatitis
e.g. pancreatic neoplasia, pancreatic edema
(associated with hypoproteinemia or portal
hypertension) and enlarged peri-pancreatic
structures, can have identical ultrasonographic
appearance to pancreatitis. Fine needle aspirates
of cavitary lesions may be useful to distinguish
abscess from pseudocyst.

Prognostic Indicators
Stratifying the severity of pancreatitis is useful
when deciding how aggressive to be with
medical and nutritional support, and in offering a
prognosis. Severe pancreatitis requires aggressive
support and carries a guarded prognosis, whereas
mild pancreatitis often responds to short term
symptomatic therapy and has agood prognosis.
Clinical and clinicopathological criteria can be
used to predict the severity of acute pancreatitis.
The presence of shock or abnormalities such as
oliguria, azotaemia, icterus, markedly elevated
transaminases, hypocalcaemia, hypoglycaemia,
hypoproteinaemia, acidosis, leukocytosis,
falling haematocrit, thrombocytopaenia and DIC
should be considered likely indicators of severe
pancreatitis in the dog and cat.
The measurement of components of the systemic
inflammatory response such as TNF-α and
C-reactive protein, and IL-6 may also yield
information about the severity of pancreatitis that
in the future might lead to the administration of
specifi c antagonists of this response.
Potentially useful prognostic indicators that are
pancreas specifi c include assay of trypsinogen
activation peptide (TAP), trypsin complexed with
inhibitors, and phospholipase A2. Trypsinogen
activation peptide has been shown to accurately
predict severity in humans with pancreatitis. This
peptide is released when trypsinogen, a pancreas specific  enzyme, is converted to its active form
and rapidly accumulates in the urine and plasma
of dogs with experimental acute pancreatitis. In
spontaneous pancreatitis. Plasma and urinary
TAP concentrations, as well as urinary TAP to
creatinine ratio, were all increased in dogs that
died with necrotising pancreatitis. Values were
not increased in mild, interstitial pancreatitis.
Increased plasma TAP concentrations were
also present in dogs with severe renal disease.
Phospholipase A2 is elevated in dogs with severe
pancreatitis.

Morphologic assesment of severity is accomplished
in humans by use of contrast enhanced computed
tomography (CE-CT). Where lack of pancreatic
perfusion is encountered i.e. necrosis, fi ne needle
aspiration is used to distinguish infected from
sterile necrosis. Substantially reduced mortality
has been achieved by the detection and surgical
treatment of people with infected necrosis.
CE-CT has recently been reported in 2 dogs
with pancreatitis. Contrast-enhanced computed
tomography (CT) fi ndings in both dogs were
compatible with pancreatic necrosis. In one dog
managed medically for 11 days the follow-up
CT scan disclosed decreased pancreatic size and
increased contrast enhancement compatible with
partial resolution of pancreatitis.

 

Treatment
Medical treatment is based on maintaining
or restoring adequate tissue perfusion,
limiting bacterial translocation and inhibiting
infl ammatory mediators and pancreatic enzymes;
surgical treatment consists principally of restoring
biliary outfl ow, removing infected necrotic
pancreatic tissue, or coping with sequela such as
pseudocysts. No studies have critically evaluated
treatment modalities in dogs or cats with naturally
occurring pancreatitis.

Initial Management
The initial medical
management of dogs with acute pancreatitis
is based on the presenting clinical fi ndings and
the results of an initial database. Dehydration
or hypovolemia are supported with intravenous
fl uid therapy e.g. LRS or 0.9% NaCl. Potassium
and glucose should be supplemented where
necessary. The type of fl uid is tailored on the basis
of electrolyte and pH measurements to restore
normal electrolytes and acid-base balance. E.g.
vomiting and mild dehydration are usually given
crystalloids such as lactated Ringer’s solution at
a rate that will provide maintenance and replace
both defi cits and ongoing losses over a 24h
period. Dogs with signs of shock require more
aggressive support. The volume defi cit can
be replaced with crystalloids at an initial rate
of of 60-90ml/kg/h, then tailored to maintain
tissue perfusion and hydration. Plasma (20ml/
kg i.v.) or colloids (eg. Hetastarch, Dextran 70:
10-20 ml/kg/day i.v.). may be indicated in the
presence of hypoproteinemia or shock. Colloids
such as dextran 70 and hetastarch may also have
antithrombotic effects that help maintain the
microcirculation.

Insulin therapy is initiated in diabetic patients
Where vomiting is a problem, antiemetics
(metoclopramide or chlorpromazine) and antacids
(e.g. famotidine) can be prescribed.
Prophylactic broad-spectrum antibiotics (e.g.
amoxicillin ± enrofl oxacin depending on severity)
may be warranted in patients with shock, fever,
diabetes mellitus or evidence of breakdowm of
the GI barrier.
Analgesia can be provided using buprenorphine
(0.005-0.01mg/kg SC q6-12hrs) or oxymorphone
(0.1-0.2 mg/kg dogs IM, SC Q 1-3hrs). It may be
necessary to administer low dose sedation with
acepromazine (0.01mg/kg IM) to patients who
become dysphoric after opioids. Buprenorphine
is a partial agonist and may antagonise the
administarion of more potent analgesics in
animals with severe pain. A transdermal fentanyl
patch (Duragesic, Janssen) applied to a clipped
clean area of skin provides a longer duration
of analgesia in dogs (10-20kg, 50μg/hr patch q
72hrs). Adequate fentanyl levels are not attained
for between 6-48 hrs after application, so another
analgesic should be administered in the short
term. The author avoids using non-steroidal
analgesics in patients with acute pancreatitis due
to concerns for GI ulceration, renal failure and
potentially hepatotoxicity.

Specific Therapy
Many dogs with acute
pancreatitis respond to fl uid therapy and nothing
by mouth for 48h. Hence, specifi c therapy is
usually reserved for dogs that do not respond to
fl uid therapy or those with signs of multiorgan
system involvement or DIC.
The specifi c treatment of pancreatitis has evolved
along two paths, 1. Stopping further pancreatitis
from occurring, and 2. Limiting the local and
systemic consequences of pancreatitis.
Therapies aimed at inhibiting pancreatic secretion
(e.g. glucagon, somatostatin) or the intracellular
activation of proteases (e.g. gabexate mesilate)
which have been of benefi t in ameliorating
the severity of experimental pancreatitis have
shown little benefi t in the treatment of patients
with spontaneous pancreatitis, unless they are
given before pancreatitis is induced (e.g. before
ERCP). The lack of success with inhibiting the
progression of spontaneous pancreatitis has led
to increased emphasis on damage limitation;
ameliorating the effects of inflammatory
mediators or pancreatic enzymes on the patient
and maintaining pancreatic perfusion.
Where a coagulopathy e.g. DIC, or hypoproteinemia
are present, or the patient with pancreatitis is
deteriorating, fresh frozen plasma (10-20ml/kg)
may be benefi cial in alleviating the coagulopathy,
hypoproteinemia and restoring a more normal
protease-antiprotease balance. Heparin (75-150IU/
kg TID) may be potentially useful in ameliorating
DIC, promoting adequate microcirculation in
the pancreas and clearing lipemic serum. In
experimental pancreatitis isovolemic rehydration
with dextran has also been shown to promote
pancreatic microcirculation in dogs. Therapy to
abrogate the systemic infl ammatory response
with antagonists of PAF (e.g lexipafant), IL-1 and
TNF-α holds promise for the future.
Oral pancreatic enzyme extracts have been
reported to reduce pain in humans with chronic
pancreatitis, though this is controversial. They
are less likely to be effective in dogs as they do
not appear to have a protease mediated negative
feedback system.

Nutritional Support
The initial aim is to identify and prevent, or treat,
nutritional factors associated with pancreatitis:
Where obesity, hyperlipidemia and dietary
indiscretion are reported it would seem prudent
to address their underlying cause in an attempt to
prevent future bouts of pancreatitis.
Precise recommendations for the dietary
management of acute pancreatitis in dogs are
hampered by the absence of controlled studies,
and are often based on empirical wisdom and a
best guess least harm approach.

The dilemma between feeding and stimulating
the pancreas:

Pancreatic secretion in healthy
dogs occurs in response to ingested nutrients,
particularly fats and amino acids delivered into
the duodenum. Pancreatic secretion in response
to food is mediated by hormones such as CCK
and secretin, parasympathetic stimulation, and
duodenopancreatic nerves. Restricting oral intake,
or providing nutrients intravenously, does not
stimulate pancreatic secretion. Thus it has been
largely accepted that to provide “pancreatic rest”
oral intake should be withheld until clinical signs
resolve, or when signs persist for 72-96hrs that
parenteral nutrition is introduced. This dogma is
still prevalent in veterinary and human medicine.
However, there is growing evidence in people,
and animals, that enteral nutrition is superior
to parenteral nutrition in the treatment of acute
pancreatitis. Jejunal feeding (distal to the site of
pancreatic stimulation) does not exacerbate acute
pancreatitis in people or experimental animals.
People with acute pancreatitis fed via jejunostomy
tubes (these can be oral transpyloric tubes), have
lower morbidity, shorter hospital stays and
less cost than those treated with TPN. As it is
now feasible to place jejunostomy tubes nonsurgically
in dogs, through the nose, esophagus
or stomach, clinical application of this feeding
strategy is not restricted by a surgical procedure.
However, it remains open whether dogs with
acute pancreatitis really require jejunal delivery
of nutrients. There is evidence that the pancreas
of dogs with acute experimental pancreatitis,
and people with naturally occurring severe
pancreatitis, is not as amenable to stimulation
as the normal pancreas. Dogs recovering from
naturally occurring pancreatitis have also been
shown to have subnormal circulating TLI
concentrations suggesting that pancreatic enzyme
synthesis is downregulated. In addition, it appears
that the major benefi ts of enteral support in acute
pancreatitis in people and experimental dogs are
due to reductions in the systemic infl ammatory
response and the translocation of enteric bacteria
rather than a reduction in pancreatic stimulation.
Intestinal permeability and morbidity in dogs with
parvovirus are positively impacted by feeding a
liquid diet (41%protein, 18% fat, 3%CF) through
a nasoesophageal tube supporting the concept
that enteral feeding in general, rather than jejunal
delivery, is the reason for the benefi cial effects of
EN, though this needs to be critically evaluated.
Resistance to enteral feeding of dogs with
pancreatitis is anticipated, despite evidence of a
benefi cial effect. One common argument used to
promote PN in dogs with pancreatitis is that they
vomit too frequently to be fed enterally. However,
recent studies in dogs with parvovirus should
also help to allay this fear as these dogs tolerated
nosesophageal feeding despite severe vomiting
and diarrhea, with enterally fed dogs showing
faster recovery rates, greater body weight gains
and lower intestinal permeability than dogs that
were held NPO.
This is not meant to imply that parenteral
nutrition should be discarded, but it’s use
be restricted to patients that really need it,
for instance those in whom caloric intake is
severely and persistently impaired by persistent
vomiting. When parenteral nutrition is indicated
a choice has to be made between total and partial
parenteral nutrition. Partial parenteral nutrition
(PPN) is a more practical and manageable
procedure than TPN in most settings and has
been shown to be a safe and effective way of
providing nutrition to dogs with pancreatitis
and gastrointestinal disease. Interestingly dogs
that received a combination of enteral and PPN
survived more often than those receiving PPN
exclusively.

What diet should be fed to dogs recovering from pancreatitis?
Free choice feeding is usually resumed
when the appetite returns and vomiting and
abdominal pain have subsided. Fat is frequently
regarded as the major stimulus for CCK release
and pancreatic secretion. However amino
acids are also potent stimulators of pancreatic
enzyme secretion and they are not restricted.
Perhaps a more rational basis for fat restriction
(?<15%DM) is the presence of hyperlipidemia.
Avoidance of other dietary factors associated
with pancreatitis, such as high fat diets, and
high fat protein restricted diets designed for
struvite dissolution, that have a nutrient profi le
similar to diest known to induce pancreatitis in
dogs, is also reasonable. Obesity, a risk factor
for pancreatitis, should be controlled with a
balanced nutritional approach. Elemental diets
cause a similar degree of pancreatic stimulation
as normal diets.

Patient Monitoring
Minimal monitoring for stable patients
includes regular assessment of vital signs and
fl uid and electrolyte balance. In those with
systemic abnormalities, monitoring should be
more aggressive and may include vital signs,
weight, haematocrit, total protein, fl uid intake
and output, blood pressure (central venous
and arterial), electrolytes and glucose, acidbase
status, platelets and coagulation status.
Monitoring pancreas specifi c markers and
clinical signs on a sequential basis should
help to support resolution or progression of
pancreatic infl ammation.
Ultrasound-guided fi ne needle aspiration of
the pancreas may enable infected pancreatic
necrosis to be detected. Ultrasonography may
also enable detection of delayed consequences
of acute pancreatitis such as pancreatic
abscessation, pseudocyst formation and biliary
obstruction.

Surgical intervention
Surgery is potentially indicated to remove
devititalized tissue in patients with infected
pancreatic necrosis and to investigate and relieve
persistent biliary obstruction. The removal or
drainage of abscesses is another indication
for surgery. Resection or surgical drainage of
pancreatic pseudocysts is not always necessary
as these can resolve spontaneously or following
percutaneous drainage. Pancreatitis that is
recurrent or is unresponsive to treatment may
also require surgery to confirm a diagnosis and to
exclude pancreatic cancer.

Prognosis
The prognosis for dogs with mild acute pancreatitis
is good. Severe or recurrent pancreatitis is
associated with a guarded prognosis.

 

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