Feline Acute Pancreatitis—Important Species Differences

Peri-pancreatic fat necrosis and acinar cell necrosis are now recognised as an important cause of morbidity and mortality in the domestic cat. Reports of this condition were uncommon prior to the early 1990s, probably related to difficulties in diagnosis as well as low incidence of disease. Some of the difficulties in the diagnosis and treatment of this disorder may have, in fact, related to preconceived notions about the same disorder in the dog. Like many other companion animal disorders, there are important differences in the natural history of the disease between cats and dogs. This manuscript will attempt to provide an overview of those differences.

History

Siamese cats were reported to be at increased risk for the disease in the first retrospective study of feline pancreatitis. ¹ A more recent study suggests that most cases of pancreatitis are seen in the domestic short hair breed. ² Lethargy (100%) and partial to complete anorexia (97%) are the most frequently reported clinical signs in cats with acute pancreatitis, ^1,2 but, of course, these clinical signs are not pathognomonic for pancreatitis. Lethargy and anorexia are the most important clinical signs in many feline diseases. Gastroenterological signs are sporadic and less frequently reported. For example, vomiting (35%) and diarrhoea (15%) were less frequently reported clinical signs in a retrospective study of 40 cases of feline acute pancreatitis. ¹ Similar findings were reported in a more recent study of feline pancreatitis. ² In canine acute pancreatitis, vomiting (90%) and diarrhoea (33%) appear to be more important clinical signs. ³

Physical examination findings

Physical examination findings in cats with acute pancreatitis include dehydration (92%), tachypnoea (74%), hypothermia (68%), icterus (64%), tachycardia (48%), abdominal pain (25%), abdominal mass (23%), dyspnoea (20%), ataxia (15%), and fever (7%). ^1,2,4,5 These findings clearly suggest that a ‘textbook’ description of acute pancreatitis (eg, vomiting, diarrhoea, abdominal pain, and fever) is uncommonly seen in the domestic cat. Many of these physical examination findings are more commonly reported in canine acute pancreatitis. For example, abdominal pain (58% in dogs; 25% in cats) and fever (32% in dogs; 7% in cats) are more commonly reported in dogs with acute pancreatitis. ³

Laboratory findings

In 40 cats with spontaneous acute pancreatitis, laboratory abnormalities included: normocytic, normochromic regenerative anaemia (55%), leucocytosis (30%), leucopenia (15%), hyperglycaemia (64%), azotaemia (57%), hypocalcaemia (45%), hypokalaemia (56%), hypoalbuminaemia (24%), hyperbilirubinaemia (64%), hypercholesterolaemia (64%), and elevations in serum alanine aminotransferase (68%) and alkaline phosphatase (50%) activities. ¹ Similar changes were reported in a more recent retrospective review of feline acute pancreatitis. ² Thus, changes in red blood cell counts, serum activities of liver enzymes, and serum concentrations of bilirubin, glucose, and cholesterol are fairly consistent findings in spontaneous feline acute pancreatitis, just as they are in the canine disorder. Important differences between cats and dogs appear to be reflected in white blood cell counts and serum calcium concentrations. Leucocytosis is a more important clinical finding in the dog (62% in dogs; 30% in cats). ³ Leucopenia is sometimes seen instead of leucocytosis in cats, and a worse prognosis has been attributed to leucopenia in the cat. ¹ Hypocalcaemia also appears to be a more frequent finding in cats (3–5 % in dogs; 45–50% in cats). ^1,2,3,6 Hypocalcaemia (total and serum ionized) may result from several mechanisms, eg, acid-base disturbances, peripancreatic fat saponification, and/or parathormone resistance. ⁷ Regardless of the mechanism, hypocalcaemia appears to confer a worse clinical prognosis in cats—greater morbidity and mortality were reported in association with hypocalcaemia in a recent retrospective report of feline acute pancreatitis. ^2,6 This finding suggests that cats should be monitored fairly closely for the development of hypocalcaemia. The value of trypsinogen-like immunoreactivity (TLI) in the diagnosis of this disease is still unsettled at this time. Two unpublished abstracts have suggested that elevations in serum TLI occur early in feline acute pancreatitis, ^8,9 but another study was unable to show similar elevations. ¹⁰ The value of this assay will require additional study. Serum amylase and lipase activities do not appear to be useful in the diagnosis of feline acute pancreatitis, ⁸ whereas these enzyme activities may still have some clinical utility in the diagnosis of canine acute pancreatitis. ³ Assays of the trypsinogen activation peptide (asp-asp-asp-asp-lys) appear to have some promise based on experimental studies, but similar studies have not yet been performed in spontaneous disease. ¹¹

Imaging findings

The radiographic findings of acute pancreatitis in the domestic cat have not been very well characterised. It has been suggested that the radiographic findings of acute pancreatitis in the dog (eg, increased density in the right cranial abdominal quadrant, left gastric displacement, right duodenal displacement, and gas-filled duodenum/colon) ¹² are similar in the cat. This statement has not been very well substantiated. Indeed, in several recent reports, many of these radiographic findings were not reported in cats with documented acute pancreatic necrosis. ^1,2,4,5 In spontaneous clinical cases, hepatomegaly and abdominal effusion are the most common radiographic findings. ^2,4 Hypoechoic pancreas, hyperechogenicity of the peripancreatic mesentery, and peritoneal effusion have been observed with abdominal ultrasonography in some cats with spontaneous acute pancreatitis. ^2,4,13 The sensitivity and specificity of this imaging modality have not yet been determined.

Aetiology/pathogenesis

The aetiology of this disorder is not completely understood. Biliary tract disease (eg, cholangiohepatitis), hypercalcaemic disorders, organophosphate poisoning, ischaemia, trauma, idiosyncratic drug reactions (eg, glucocorticoids), infection (Eurytrema procyonis flukes, feline infectious peritonitis, Toxoplasmosis), and lipodystrophy have been suggested as potential causes of acute pancreatitis in the cat. However, good evidence exists only for organophosphate poisoning, ischaemia, trauma, infection, and lipodystrophy. Pathology in the distal common bile duct (eg, infection, calculus, etc.) could predispose to acute pancreatitis because of the functional relationship between the major pancreatic duct and common bile duct sphincters in the cat. ¹⁴ Indeed, perfusion of the major pancreatic duct with bile salts produces marked structural changes in the pancreatic duct and pancreas. ^{15 –17} Necropsy reports, however, have not revealed this to be a common cause of pancreatic disease in the cat. Hypercalcaemia has been suggested as a cause of acute pancreatitis in cats because of the relationship established in humans, and because of an association recently reported in dogs. ³ Acute experimental hypercalcaemia does indeed cause acute pancreatic necrosis and pancreatitis in cats, ^18,19 but it is probably not very clinically relevant. Chronic hypercalcaemia, a more clinically relevant condition, is not associated with any changes in pancreatic morphology. ²⁰ Glucocorticoid administration has also been suggested as a cause of acute pancreatitis (especially in the dog), but the evidence for causality is not very substantial. Organophosphate poisoning is a potential cause of acute pancreatitis in the cat, ²¹ but clinical reports suggest that it may not be an important cause of acute pancreatitis in cats. Alterations in pancreatic blood flow and/or microvascular permeability may be more important mechanisms in the pathogenesis of acute pancreatitis in cats. ^{22 –24} Acute oedematous pancreatitis (a mild, frequently asymptomatic form of the disease) is readily converted to an acute haemorrhagic pancreatitis through increases in microvascular permeability induced by 16,16-dimethyl prostaglandin E2 administration in cats. ²³ Trauma, infection (eg, flukes, FIP, Toxoplasmosis) and lipodystrophy have all been cited as occasional causes of acute pancreatitis in cats. As with the dog, it is likely that other unrecognised causes of acute pancreatitis also exist in the cat.

More recent studies suggest that pre-existing inflammatory bowel disease may be an important risk factor for the development of pancreatitis (and cholangiohepatitis) in cats. ^25,26 There are several reasons, or contributing factors, for this association: (1) High incidence of feline inflammatory bowel disease—IBD is a common disorder in the domestic cat. ²⁶ In some veterinary hospitals and specialty referral centres, IBD is the most common gastrointestinal disorder in cats. (2) Clinical symptomatology— vomiting is the most important clinical sign in cats affected with IBD. ²⁶ Chronic vomiting predisposes cats to raised intra-duodenal pressure and pancreaticobiliary reflux. (3) Pancreaticobiliary anatomy—unlike the dog, the sphincter of Oddi is a common (physiological and anatomic) channel at the duodenal papilla. ¹⁴ Thus, reflux of duodenal contents perfuses both pancreatic and biliary systems. (4) Intestinal microflora—compared to the dog, cats have a much higher bacterial load (10⁸ vs 10⁴ organisms/ml) in the proximal small intestine. ^27,28 Thus, duodenal reflux may induce more pathology in the cat.

Prior gastrointestinal tract disease also confers increased risk for the development of acute pancreatic necrosis in the dog. ²⁹ Unlike the cat, however, other risk factors, eg, overweight body condition and endocrinopathies (diabetes mellitus, hyperadrenocorticism, hypothyroidism) also increase the risk of the disease in the dog.

Therapy

Supportive care continues to be the mainstay of therapy for acute pancreatitis. Thus, efforts should be made to sustain blood and plasma volume, correct acid/base and electrolyte disorders, place the pancreas in physiologic rest (NPO), and treat any complications that might develop. Important complications of acute pancreatitis in cats include disseminated intravascular coagulation, thromboembolism, cardiac arrhythmia, sepsis, acute tubular necrosis, pulmonary edema and pleural effusion. A recent study in an experimental feline model of acute pancreatitis suggests that low-dose dopamine infusion (5 μg/kg/min) diminishes the severity of the disease. ³⁰ Dopamine treatment has not yet been studied (or reported) in cats with spontaneous disease. In the same animal model, E coli has been shown to readily translocate from the colon to the inflamed pancreas. ³¹ High colonisation rates suggest that bacteria may spread to the inflamed pancreas more frequently than is currently thought, and that broad spectrum antibiotics may be appropriate in suspected cases of feline acute pancreatitis.