Page 649 - Small Animal Internal Medicine, 6th Edition

CHAPTER 37 The Exocrine Pancreas 621

without pancreatitis (Furrow et al., 2012). Another study
identified several mutations of the canine CFTR gene in dogs
VetBooks.ir both with and without pancreatitis but no significant asso-
ciation with disease (Spadafora et al., 2010). More studies are
necessary to elucidate the role of mutations in pancreatitis
in dogs.
If too much trypsin autoactivates in the pancreas, the pro-
tective mechanisms are overwhelmed and a chain reaction
occurs whereby activated trypsin activates more trypsin and
the other enzymes in the pancreas. This results in pancreatic
autodigestion, inflammation, and peripancreatic fat necrosis,
which leads to focal or more generalized sterile peritonitis.
There is an associated systemic inflammatory response (SIR)
in even the mildest cases of pancreatitis. Many other organs
may be involved, and in the most severe cases there is mul-
tiorgan failure (MOF) and diffuse intravascular coagulation
FIG 37.1 (DIC). The circulating protease inhibitors α 1 -antitrypsin
Histopathology of a section of normal canine pancreas (α 1 -protease inhibitor) and α-macroglobulin play a role in
showing two paler staining islets of Langerhans and removing trypsin and other proteases from the circulation.
exocrine acini surrounding them. Note that the islets make
up only 10% to 20% of the volume of the pancreas. Saturation of these protease inhibitors by excessive amounts
of circulating proteases contributes to the systemic inflam-
mation, but generalized neutrophil activation and cytokine
ACUTE PANCREATITIS release are probably the primary cause of SIR.
The previous paragraph has described the final common
Etiology and Pathogenesis pathway of acute pancreatitis in dogs and cats, but the under-
Understanding of the pathophysiology of acute pancreatitis lying cause of the disease is often unknown (see Table 37.3).
in humans has increased in recent years with the discovery There appears to be a strong breed relationship for pancreati-
of hereditary mutations of trypsin, which predispose to pan- tis in dogs, so hereditary causes are likely to be a factor. Many
creatitis; the pathophysiology of this disease is believed to be of the previously reported supposed causes in dogs are likely
similar in dogs and cats. The final common pathway in all triggers for disease in genetically susceptible individuals.
cases is the inappropriate early activation of trypsinogen in
the pancreas as a result of increased autoactivation of tryp- Clinical Features
sinogen and/or reduced autolysis of prematurely activated Acute pancreatitis typically affects middle-aged dogs and
trypsin. Trypsin is the major protease secreted by the pan- cats, although very young and very old individuals may also
creas, and inappropriate early activation in the acinar cells be affected. Terrier breeds, Miniature Schnauzers, and
would obviously cause autodigestion and severe inflamma- domestic short-haired cats appear to be at increased risk for
tion. Protective mechanisms therefore exist to prevent early acute pancreatitis, although any breed or cross-breed can be
activation. Trypsin is stored in zymogen granules in the pan- affected. Some dog breeds appear to be underrepresented in
creatic acini as the inactive precursor trypsinogen. Up to clinical studies, particularly large and giant breeds, although
10% of trypsinogen gradually autoactivates normally within Labrador Retrievers and Husky types (the latter particularly
the granules but is inactivated by the action of other trypsin in Australia) are often affected. Breed relationships suggest
molecules and by the cosegregating protective molecule, an underlying genetic tendency, mirroring the situation in
pancreatic secretory trypsin inhibitor (PSTI; also known as humans. It is likely that the disease is multifactorial, with a
serine protease inhibitor Kazal type 1, or SPINK1). Genetic genetic tendency and superimposed triggering factors. For
mutations of trypsinogen, which make it resistant to hydro- example, eating a high-fat meal may be a trigger for a sus-
lysis, and/or of PSTI predispose to pancreatitis in people and ceptible terrier. Some studies suggest a slight increase in risk
are also likely to occur in some dogs (Table 37.3). A variety in female dogs, whereas others show no gender predisposi-
of mutations of the cystic fibrosis transmembrane conduc- tion. Obesity has been suggested as a predisposing factor in
tance regulator (CFTR) gene also predispose to pancreatitis dogs, but it is unclear whether this is a cause or whether it
in humans. Studies of mutations predisposing to acute pan- is cosegregating with disease (i.e., breeds at high risk for
creatitis in dogs have focused on Miniature Schnauzers. acute pancreatitis may coincidentally also be breeds with a
Initial studies showed no mutations in the cationic trypsino- high risk for obesity). In some cases in cats there is a recog-
gen gene in individuals with pancreatitis in this breed but nized association with concurrent cholangitis, inflammatory
did find variations in the gene coding SPINK1 (Bishop et al., bowel disease, and renal disease. Cats with acute pancreatitis
2004, 2010). However, a more recent study questioned the are also at high risk for hepatic lipidosis.
significance of this finding because SPINK1 mutations were The history in dogs often includes a trigger such as a high-
found in Miniature and Standard Schnauzers, both with and fat meal or engorging (see Table 37.3). Recent drug therapy