BVSc (Hons) MMedVet (Med) PhD Dipl. ECVIM (Internal Medicine)
Bryanston Veterinary Hospital
PO Box 67092, Bryanston, 2021, South Africa
Acute pancreatitis (AP) is a common disorder which may result in death if not diagnosed in a timely fashion. This frequently encountered disease remains difficult to diagnose because the clinical signs, physical examination findings, and clinicopathologic changes are often non-specific. Therefore, knowledge recognition of the clinical manifestations of this disorder is important.
The initiating event of acute pancreatitis is the premature activation of digestive zymogens within the acinar cell. Premature activation of digestive zymogen results in acinar cell necrosis and pancreatic autodigestion. In acute pancreatic necrosis, protein synthesis and intracellular transport to the Golgi complex appear to be normal, but digestive zymogens then become co-localized along with lysosomal hydrolases in large vacuoles. Cell biology studies have revealed that lysosomal and zymogen granule fractions become co-localized through a process known as crinophagy, a process used by many cells to degrade accumulated secretory products when the need for secretion is no longer present. Although this process takes place in other cells without adverse consequences, it can be lethal in pancreatic acinar cells because of the peculiarity of their secretion products (digestive zymogens). Lysosomal hydrolases, such as cathepsin B and N-acetyl glucosaminidase, activate trypsinogen to the active trypsin form, and the enhanced fragility of these large vacuoles permits release of active enzyme into the cell cytoplasm. Trypsin acts auto-catalytically to activate other trypsinogen molecules and other zymogens, each inducing a unique chemical pathology in pancreatic and extra-pancreatic cells. A variety of inflammatory mediators and cytokines (tumour necrosis factor-α, interferon-α, interferon-γ, platelet-activating factor), interleukins (IL-1, IL-2, IL-6, IL-8, IL-10), nitric oxide, and free radicals are involved in the further evolution of pancreatic acinar cell necrosis and inflammation.
Yorkshire terriers are at increased risk of developing AP, whereas miniature poodles and Labrador retrievers are at decreased risk for AP. Breed predisposition may suggest a hereditary component to AP. Hereditary pancreatitis in humans can occur in association with a genetic defect of lipoprotein lipase, in individuals with hypertriglyceridaemia and diabetes mellitus, or as an autosomal dominant trait, of unknown aetiology, with a chronic recurrent presentation, and an early onset (usually in childhood). Further investigation is needed to determine if familial lipid metabolism disorders, or other genetic defects, predispose Yorkshire terriers to AP.
The mean age of dogs with AP is 8 years. Dogs with AP may be middle to older age dogs because several of the risk factors for AP (diabetes mellitus, hyperadrenocorticism, and hypothyroidism) develop in middle to older aged dogs. Obesity, which is another risk factor for AP may also be a problem of middle-aged dogs. Additionally, the increased age of dogs with AP could be a reflection of a degenerative pancreatic or extra-pancreatic process, or a result of accumulating metabolic disorders that increase the risk of AP.
Males and neutered females are at increased risk compared to intact female dogs. This finding may indicate that sex gender specific factors are involved in the pathophysiology of AP.
Overweight and obese dogs are at an increased risk of developing AP. Increased body mass index has been reported to be a risk factor and a poor prognostic indicator in humans. Increased retroperitoneal and peri-pancreatic fat deposition is thought to increase the risk of peri-pancreatic fat necrosis in humans.
Diabetes mellitus, hyperadrenocorticism, and hypothyroidism are all associated with increased risk for AP. It is possible that lipid metabolism disorders are responsible for the increased risk. Hypertriglyceridaemia is a risk factor in humans and is seen in dogs with diabetes mellitus, hyperadrenocorticism, and hypothyroidism. Hypertriglyceridaemia has been reported in association with naturally occurring canine AP. Experimentally induced hypertriglyceridaemia initiates pancreatic injury but does not seem to be a consequence of experimentally induced pancreatitis in the dog. These findings would support a hypothesis of hypertriglyceridaemia being a risk factor, rather than a consequence of canine AP. However, many other metabolic abnormalities could be involved.
Prior gastrointestinal disease
Prior gastrointestinal disease (colitis, gastrointestinal parasites, or inflammatory bowel disease) is a risk factor for canine AP. Chronic inflammation of the gastrointestinal tract, e.g., proximal duodenum and transverse colon, may increase local inflammation and predispose to AP.
Although epilepsy is a risk factor for canine AP, the reason for this association is unknown. Proposed aetiologies are anticonvulsant therapy or pancreatic ischaemia during seizure activity.
Possible risk factors
Thromboembolism has been observed more commonly in dogs with AP compared to control dogs. However, thromboembolism may develop as a result of AP and may not necessarily be a risk factor for AP. On the one side the proteolytic enzymes released from the pancreas cause endothelial damage resulting in infarct and thrombus formation. On the other hand, it is conceivable that an underlying coagulopathy, such as that associated with hyperadrenocorticism, causes infarct and thrombus formation, impairing pancreatic blood flow, resulting in AP.
Atherosclerosis was more common in dogs with AP compared to control dogs. Hypothyroid dogs are predisposed to atherosclerosis however, atherosclerosis was also observed in a dog that had no evidence of hypothyroidism on post mortem examination. In humans, hypertriglyceridaemia is a risk factor for pancreatitis, but its role in atherosclerosis remains controversial. Hypertriglyceridaemia may be a risk factor for both AP and atherosclerosis in the dog.
Administration of trimethoprim/sulphonamide antibiotics
Sulphonamides have been reported as a risk factor in humans, and in some of the human patients the association was confirmed with re-challenge. Hypersensitivity reaction or toxic effects are suspected. Although trimethoprim/sulphonamide administration has not been reported as a risk factor for AP in dogs, other adverse reactions have been documented, with some suspected of being immune-mediated.
Abdominal ultrasonographic abnormalities are consistent with a diagnosis of AP more frequently than abdominal radiographic abnormalities. However, in some cases, abdominal ultrasonographic abnormalities are not apparent, while abdominal radiographs are suggestive of AP. Therefore, it is recommended that both imaging studies should be performed when faced with a suspected case of AP. Additionally, abdominal radiographs are a valuable diagnostic tool in any case of suspected AP because other causes of gastrointestinal disease must be ruled out. Abdominal radiographs are not suggestive of AP in 76% of dogs with histopathological confirmation of AP. Therefore, in dogs suspected of having AP, abdominal ultrasonography should be performed even if abdominal radiographs are not suggestive of AP.
The main radiographic abnormalities associated with AP are increased radio-opacity and loss of detail in the right cranial quadrant, gas filling and displacement of descending duodenum and/or stomach, widening of gastric/duodenal angle, and abdominal fluid leading to local increased opacity. The described changes are not always present and are non-specific. However, abdominal radiographs are a valuable tool in ruling out other gastrointestinal diseases.
Ultrasonographic findings associated with AP include hypoechoic pancreatic parenchyma, hyperechoic mesentery, pancreatic enlargement, peritoneal effusion, and identification of pancreatic cysts, pseudocysts, or masses. One study in dogs with fatal acute pancreatitis indicated that ultrasonographic examination supported a diagnosis of pancreatitis in 23/34 dogs (68% sensitivity).
FELINE EXOCRINE PANCREATIC DISEASE
The aetiologies of acute necrotizing pancreatitis are probably not yet completely recognized. Biliary tract disease, gastrointestinal tract disease, ischaemia, pancreatic ductal obstruction, infection, trauma, organophosphate poisoning, and lipodystrophy all have known associations with the development of acute necrotizing pancreatitis in the cat. Although hypercalcaemia, idiosyncratic drug reactions, and nutritional causes have been suggested, they are poorly documented.
Concurrent biliary tract disease
Concurrent biliary tract pathology has a known association with acute necrotizing pancreatitis in the cat. Cholangitis is the most important type of biliary tract disease for which an association has been made, but other forms of biliary tract pathology (e.g., stricture, neoplasia, and calculus) have known associations. Epidemiologic studies have shown that cats affected with suppurative cholangitis have a significant increased risk for pancreatitis. The pathogenesis underlying this association is not entirely clear but partly relates to the anatomic and functional relationship between the major pancreatic duct and common bile duct in this species. Unlike the dog, the feline pancreatico-biliary sphincter is a common physiological and anatomic channel at the duodenal papilla. Mechanical or functional obstruction to this common duct readily permits bile reflux into the pancreatic ductal system.
Concurrent GI tract disease
Like concurrent biliary tract disease, inflammatory bowel disease (IBD) is an important risk factor for the development of acute necrotizing pancreatitis in the cat. Several factors appear to contribute to this association:
- High incidence of inflammatory bowel disease.
- Vomiting is the most important clinical sign in cats with IBD, which raises intra-duodenal pressure and increases the likelihood of pancreatico-biliary reflux.
- The pancreatico-biliary sphincter is a common physiological and anatomic channel at the duodenal papilla, thus reflux of duodenal contents would perfuse pancreatic and biliary ductal systems.
- Compared to dogs, cats have a much higher concentration of aerobic, anaerobic and total bacteria in the proximal small intestine. Bacteria readily proliferate in the feline small intestine because of differences in gastrointestinal motility and immunology. If chronic vomiting with IBD permits pancreatico-biliary reflux, a duodenal fluid containing a mixed population of bacteria, bile salts, and activated pancreatic enzyme would perfuse the pancreatic and biliary ductal systems.
Ischaemia (e.g., hypotension, cardiac disease) can either be a cause or consequence of obstructive pancreatitis in the cat. Inflammation and oedema reduce the elasticity and distensibility of the pancreas during secretory stimulation. Sustained inflammation increases pancreatic interstitial and ductal pressure which serves to further reduce pancreatic blood flow, organ pH, and tissue viability. Acidic metabolites accumulate within the pancreas because of impaired blood flow. Ductal decompression has been shown to restore pancreatic blood flow, tissue pH, and acinar cell function.
Pancreatic duct obstruction
Obstruction of the pancreatic duct (e.g., neoplasia, pancreatic flukes, calculi, and duodenal foreign bodies) is associated with the development of acute necrotizing pancreatitis in some cases. Pancreatic ductal obstruction has marked effects on pancreatic acinar cell function. During ductal obstruction, ductal pressure exceeds exocytosis pressure and causes pancreatic lysosomal hydrolases to co-localize with digestive enzyme zymogens within the acinar cell.
Siamese cats were initially reported to be at increased risk for the disease, however, clinical case surveys of the past 10 years suggest that most cases of feline pancreatitis are seen in the Domestic Short Hair breed. Anorexia (87%) and lethargy (81%) are the most frequently reported clinical signs in cats with acute pancreatitis, but these clinical signs are not pathognomonic for pancreatitis. GI tract signs are sporadic and less frequently reported in the cat. Vomiting and diarrhoea are reported in only 46% and 12% of cases, respectively. In dogs, vomiting (90%) and diarrhoea (33%) are more important clinical signs.
Physical examination findings in cats with acute necrotizing pancreatitis include dehydration (54%), hypothermia (46%), icterus (37%), fever (25%), abdominal pain (19%), and abdominal mass (11%). These findings suggest that a “classic textbook” description of acute pancreatitis (e.g., vomiting, diarrhoea, abdominal pain, and fever) is not consistently seen in the domestic cat. Many of these physical examination findings are more commonly reported in canine acute pancreatitis. Abdominal pain (58% in dogs; 19% in cats) and fever (32% in dogs; 25% in cats), for example, are more commonly reported in dogs with acute pancreatitis.
In cats affected with acute necrotizing pancreatitis, laboratory abnormalities have included: normocytic, normochromic, regenerative or non-regenerative anaemia (38%), leukocytosis (46%), leukopenia (15%), hyperbilirubinaemia (58%), hypercholesterolaemia (72%), hyperglycaemia (45%), hypocalcaemia (65%), hypoalbuminaemia (36%), and elevations in liver enzyme activity. Changes in red blood cell counts, serum activities of liver enzymes, and serum concentrations of bilirubin, glucose, and cholesterol are fairly consistent findings in feline acute necrotizing pancreatitis, just as they are in dogs. Important differences between cats and dogs appear to be reflected in white blood cell counts and serum calcium concentrations. Leukocytosis is a more important clinical finding in the dog (62% in dogs; 46% in cats). Leukopenia is sometimes seen instead of leukocytosis in cats, and a worse prognosis has been attributed to leukopenia in the cat. Hypocalcaemia also appears to be a more frequent finding in cats (3-5% in dogs; 45-65% in cats). Hypocalcaemia may result from several mechanisms, including acid-base disturbances, peri-pancreatic fat saponification, and parathormone resistance. Regardless of the mechanism, the presence of hypocalcaemia worsens the prognosis. Thus cats should be monitored fairly closely for the development of hypocalcaemia and treatment should be initiated, accordingly.
Special tests for pancreatic function
Serum lipase and amylase activities do not appear to be elevated or of clinical value in the diagnosis of clinical pancreatitis. Serum lipase activity may still have some clinical utility in the diagnosis of acute necrotizing pancreatitis in the dog. Assays of serum lipase activity are complicated by the fact that there may be as many as five different isoenzymes circulating in the blood; consequently general serum lipase activity assays have been superseded by the development of pancreatic lipase immunoreactivity assays (e.g., cPLI, fPLI).
Serum TLI mainly measures trypsinogen but also detects trypsin and some trypsin molecules bound to proteinase inhibitors. TLI assays are species-specific, and different assays for feline (fTLI) and canine (cTLI) have been developed and validated. Serum TLI concentration is the diagnostic test of choice for feline exocrine pancreatic insufficiency because it is highly sensitive and specific for this disease in the cat, however, the use of this test in the diagnosis of feline acute necrotizing pancreatitis is less clear.
A radioimmunoassay for the measurement of pancreatic lipase immunoreactivity (fPLI) has been developed and validated in the cat, with fPLI elevations cited in preliminary reports of experimental and clinical feline acute necrotizing pancreatitis.
The radiographic findings of feline acute necrotizing pancreatitis have not been very well characterized. The radiographic hallmarks of canine acute pancreatitis have not been substantiated in the cat. Indeed, in several recent reports, many of these radiographic findings were not reported in cats with documented acute pancreatic necrosis.
Enlarged, irregular, and/or hypoechoic pancreas, hyperechogenicity of the peri-pancreatic mesentery, and peritoneal effusion have been observed with abdominal ultrasonography in many cats with spontaneous acute pancreatitis. The specificity of this imaging modality appears to be high (>85%), but the sensitivity has been reported as low as 35% in some studies. The low sensitivity suggests that imaging the pancreas in cats with pancreatitis is technically more difficult than imaging the pancreas in dogs or that the ultrasonographic appearance of pancreatitis in cats differs from that reported for dogs.
- Maintenance of fluid and electrolyte balance while the pancreas is rested by withholding food, and thereby allowed to recover from the inflammatory insult.
- Oral intake should probably only be limited in cases with severe vomiting and then for a short period.
- As soon as the vomiting stops, start small amount of water.
- A low fat food is then gradually introduced (intestinal formula diets).
- Cats with pancreatitis should not be starved because of possible hepatic lipidosis.
- Anti-emetics, such as metaclopramide or ondansetron, if vomiting is intractable.
- Withhold oral food and water for 24-60 hours.
- Maintain normal fluid and electrolyte balance.
- Plasma transfusion can be life-saving in critical animals.
- Correct any drug or toxin exposure that may have precipitated disease.
- Antibiotic therapy often given, but infection rarely present.
- Surgical intervention rarely helpful.
- Gradually reintroduce a low-fat moderate protein content diet.
- Feeding tube placement and feeding hydrolysed/partially digested liquid diets in severe cases.
- Avoid high fat content diets and obesity.
- Complete recovery is possible
- Feed low-fat diet to animals with recurrent disease.