Acute pancreatitis

Inflammation of the pancreas occurs when the enzymes secreted by the pancreas become prematurely active in the pancreatic duct and attack the pancreatic tissue. The process starts when the secretion of pancreatic enzymes is partially inhibited, leading to an abnormal accumulation inside the cell. Under physiological conditions, various protective mechanisms in the pancreas prevent the activation of these enzymes:

1. Digestive enzymes are synthesized as inactive proenzymes.
2. In pancreatic cells, the proenzymes are isolated in cytoplasmic vacuoles and do not come into contact with other enzymes.
3. The pancreas produces pancreatic secretory trypsin inhibitor.
4. Systemic inhibitors such as plasma proteases are also available.

When these protective mechanisms fail or are overcome, pancreatitis is triggered by trypsin - the first enzyme to be activated. This enzyme then activates the other proenzymes, causing a cascade of alterations at different levels:

1. Local lesions: destruction of cells and the pancreatic stroma, increased vascular permeability, interstitial oedema and haemorrhage, accompanied by leukocyte infiltration, peripancreatic fat necrosis, and pain.
2. Systemic disorders: arterial hypotension and capillary vasodilation, portal venous blood stasis, hypovolaemia and compensatory peripheral vasoconstriction that further reduces blood flow to the pancreas.
3. Systemic complications: caused by digestive enzymes and vasoactive amines filtering into the abdominal cavity and blood stream. Other processes include pulmonary oedema and respiratory failure, cardiac arrhythmias, liver damage, acute kidney failure, central neurological deficits, disseminated intravascular coagulation, and multiorgan failure.

Depending on the capacity of the protective mechanisms, acute pancreatitis can vary from a mild, self-limiting disorder to a fulminant, fatal process. Mild pancreatitis presents as localised interstitial oedema, and has a favourable outcome. In severe pancreatitis, the initial interstitial oedema progresses to a self-perpetuating cycle of bleeding and necrotization, resulting in generalized failure in other organs.

Recurrent episodes of subclinical acute pancreatitis may lead to chronic pancreatitis that causes progressive fibrosis of the gland.

Symptoms

Symptoms of acute pancreatitis vary greatly, and the disease cannot be identified by pathognomonic signs.

Dogs

• Most common symptoms: acute vomiting / depression / dehydration / abdominal pain, especially in the right cranial quadrant of the abdomen / fever of inflammatory origin.
• Uncommon symptoms: weakness / tachypnoea / tachycardia / mucosal hyperaemia / hepatomegaly / often bloody diarrhoea / jaundice / abdominal distension / coagulopathy.

Cats

Acute pancreatitis is particularly difficult to diagnose in cats. Many cases are diagnosed post-mortem.

• Most common symptoms: lethargy/anorexia/dehydration/hypothermia, followed by acute emaciation and shock.
• Uncommon symptoms: vomiting/abdominal pain/palpable abdominal mass/dyspnoea/ataxia/diarrhoea. One third of cases present acute cardiac shock.

Interpretation of laboratory tests

Generally speaking, pancreatitis is a difficult pathology to diagnose, and most cases are probably overlooked. Many of the changes observed are nonspecific. Most tests may suggest pancreatitis but the findings are inconclusive, and even a normal test cannot completely rule out the disease, which must therefore be diagnosed by a process of exclusion.

Complete blood count:

Neutrophilia, sometimes with a shift to the left, is observed. Neutropenia with degenerative left shift is rare, and is associated with severe necrosis, peritonitis or sepsis. Moderate anaemia and thrombocytopaenia may occur, usually indicating subclinical disseminated intravascular coagulation. If the animal is dehydrated, haemoconcentration and elevated mean corpuscular volume (MCV) may be found. In cats, neutrophilia and anaemia may appear in the terminal phases of the disease, with nucleated red blood cells that do not regenerate.

Serum biochemistry

General parameters:

• Urea. Usually slightly elevated due to dehydration or kidney failure secondary to pancreatitis.
• ALT / Alkaline phosphatase. Usually elevated due to hepatic ischaemia, regional peritonitis, or extrahepatic biliary obstruction.
• TBIL. Almost always elevated due to hepatocellular injury and intra- or extrahepatic obstruction of the bile ducts.
• Glucose. Hyperglycaemia is common due to increased glucagon secretion and catecholamine- and cortisol-induced stress. Cats with suppurative pancreatitis may also present hypoglycaemia.
• Calcium. Mild to moderate hypocalcaemia may be observed due to calcium deposition in soft tissues. Severe hypocalcaemia can occur in cats, and is associated with a poor prognosis.
• Potassium / Phosphorus. Many cats with acute pancreatitis present hypokalaemia and hypophosphataemia.
• Albumin. Lower than normal values may be found.
• Cholesterol / Triglycerides. Usually elevated.

Pancreatic parameters:

• Amylase. May be elevated in some dogs with pancreatitis, but normal in others. However, the degree of elevation does not correspond to the severity of the disease. The pancreas is not the only source of amylase in the body; impaired kidney function can also cause an elevation of this enzyme. Amylase is not elevated in most cats with pancreatitis, so this parameter is not diagnostic.
• Lipase. May be elevated in some dogs with pancreatitis, but normal in others. This finding is only significant if lipase is three to five times higher than normal values. It is also important to bear in mind that other tissues besides the pancreas can synthesize lipase. Impaired kidney function, some liver disorders, various tumours and the administration of corticosteroids also cause an elevation of this enzyme. Lipase is usually within normal values in cats with pancreatitis.

Immunoassay:

• TLI. This test is specific for pancreatic diseases, but levels are elevated in less than 40% of dogs with pancreatitis. Administration of corticosteroids does not affect the results. The test is species-specific. In cats, levels can be altered due to enteric inflammation.
• cPLI. This test only measures pancreatic lipase. Normal values for healthy dogs determined by ELISA range from 2.2 to 102.1 μg/L, and values greater than 250 μg/L indicate pancreatitis. Impaired kidney function does not cause elevated lipase in cPLI.
  This test is currently considered the most sensitive diagnostic test for pancreatitis in dogs, and a similar method is being developed for cats, although neither is yet available.

Serum levels of pancreatitis-related proteins:

• TAP (Trypsinogen Activation Peptide) / Trypsin Complexes. Alpha1 proteinase/alpha 2-macroglobulin inhibitor: According to recent clinical studies, determination of these proteins is not useful in the diagnosis of pancreatitis.

Abdominal fluid examination:

In animals with pancreatitis, abdominal fluid analysis will determine whether the fluid is an exudate (protein > 2.5 mg/dl and nucleated cell count between 3,000 and 5,000 cells/mcl, with a predominance of non-degenerated neutrophils). Amylase and lipase values are higher than in serum.

Diagnostic imaging:

• Radiography: Although radiographic findings may be suggestive of pancreatitis, they are neither conclusive nor specific.
• Ultrasound: a highly specific technique in both dogs and cats, provided strict diagnostic criteria are applied. The quality is dependent on the experience of the operator.

Exploratory laparotomy-laparoscopy-biopsy

Pancreatic biopsy is the only test that usually provides a definitive diagnosis of canine and feline pancreatitis. The sample should be obtained from the macroscopically affected areas, trying to avoid the central area containing the pancreatic ducts. Pancreatic biopsy-related complications are very rare.

Bibliography

• HALL, J.A. (2004) : en Morgan-Bright-Swartout (Ed.): Clínica Veterinaria de Pequeños Animales ( 4ª ed.) Saunders-Elsevier, pg. 408-423.
• NELSON, R.W.; COUTO, C.G. (2003): en Mosby (Ed.): Small Animal Internal Medicine (3ª ed.) pg. 552-560.
• NEWMAN, S.; STEINER, J.; WOOSLEY, K.; BARTON, L.; RUAUX, C.; WILLIAMS, D. (2004) Journal of Veterinary Internal Medicine vol.18(4), pg. 488-493.
• STEINER, J.M. (2003) Veterinary Clinics of North America: Small Animal Practice vol. 33, nº 5, pg. 1181-1195.
• RUAUX, C.G. (2003) Clinical Techniques in Small Animal Practice vol.18(4), pg. 245-249.