Chapter 73 Diseases and Surgery of the Exocrine Pancreas

The pancreas is a V-shaped gland in the cranial abdomen composed of an exocrine portion (the acinar cells) and an endocrine portion (the islets of Langerhans). The normal functions of the exocrine pancreas are summarized in Table 73-1. The clinically important disorders of the exocrine pancreas include pancreatitis, exocrine pancreatic insufficiency, and neoplasia. Diseases of the endocrine pancreas are discussed in Chapters 34 and 35.

Table 73-1 FUNCTIONS OF THE EXOCRINE PANCREAS

* Acinar cells secrete enzymes in response to cholecystokinin, which is released into the blood from the proximal intestine when partially digested food enters the duodenum from the stomach. Proteolytic enzymes are secreted as inactive precursors (zymogens) that are not activated until they enter the intestinal tract. Enteropeptidase from the duodenal mucosa activates trypsinogen to active trypsin; trypsin then activates the other proteases and phospholipase.

† Centroacinar and duct cells produce bicarbonate-rich secretion in response to secretin released into the blood from the proximal intestine when acid enters the duodenum from the stomach.

PANCREATITIS

Pancreatitis is an acute or chronic inflammatory condition of the pancreas that develops when premature intrapancreatic activation of digestive enzymes results in progressive autodigestion of the pancreas. Clinically, pancreatitis can be acute or chronic and mild or severe. The clinical forms of pancreatitis are categorized in Table 73-2.

Table 73-2 CATEGORIES OF PANCREATITIS

Acute Pancreatitis (abrupt onset, acute episodes may recur)

Mild (Edematous)

Self-limiting

Minimal necrosis and vascular compromise

No multisystemic effects or complications

Uncomplicated recovery

Severe (Hemorrhagic)

Self-perpetuating (progressive)

Extensive necrosis and vascular compromise

Severe complications

Multisystem failure

Guarded prognosis

Chronic Pancreatitis (may be continuous and “smoldering” or recurrent and episodic)

Mild

Minimal morphologic damage

Absence of complications

Severe

Progressive irreversible destruction of acinar and islet cells

Severe pancreatic fibrosis and atrophy

Complications:

Exocrine pancreatic insufficiency

Diabetes mellitus

Extrahepatic bile duct obstruction

Key Point

Dogs most frequently develop acute pancreatitis. Cats are more likely to develop chronic pancreatitis.

Etiology and Risk Factors

In most animals with spontaneous pancreatitis, an etiology is not identified and the pathogenesis is poorly defined. Based on clinical associations found in naturally occurring cases and on various experimental models for producing pancreatitis, the following have been implicated as etiologic or predisposing factors:

• Nutrition—Obesity (dogs), long-term intake of high-fat low-protein diet

• Hyperlipidemia—As a result of recent ingestion of a fatty meal, miniature schnauzer hyperlipidemia, lipodystrophy, or endocrinopathy (e.g., hyperadrenocorticism, diabetes mellitus, or hypothyroidism)

• Reflux of duodenal contents—Into the pancreatic duct as bile, fatty acids, activated enzymes, or bacteria

• Obstruction of the pancreatic duct or papilla—As a result of duodenitis, edema, spasm, calculi, neoplasia, metaplasia, or aberrant intestinal parasite migration

• Biliary tract disease—Especially cholangitis in cats

• Gastrointestinal disease—Especially inflammatory bowel disease in cats

• Infection—For example, ascending enteric bacteria, parvovirus, feline infectious peritonitis, Toxoplasma gondii, Babesia canis, pancreatic flukes (Eurytrema procyonis), or liver flukes (Amphimerus pseudofelineus)

• Hypercalcemia—When total serum calcium exceeds 15 mg/dl, as can occur in hypercalcemia of malignancy, hyperparathyroidism, and vitamin D intoxication

• Hyperstimulation—By organophosphate toxicity, cholinergic agonists, scorpion venom, and caerulein (an analogue of cholecystokinin)

• Idiosyncratic drug reactions—Corticosteroids, potassium bromide, L-asparaginase, azathioprine, sulfonamides, etc.

• Zinc toxicosis

• Pancreatic trauma—Abdominal injury, surgery, or lithotripsy

• Pancreatic ischemia—For example, hypovolemia, thrombosis, and gastric dilatation-volvulus

• Genetic predisposition—Miniature schnauzers, etc.

Pathogenesis

Pancreatitis results from the premature intrapancrea-tic activation of trypsin and other digestive enzymes, resulting in acinar cell necrosis and pancreatic autodigestion.

• Once initiated, amplification and progression of pancreatitis involves factors such as nitric oxide, oxygen-derived free radicals, and various inflammatory mediators, cytokines, and interleukins.

• Severity is enhanced by pancreatic microvascular injury, pancreatic ischemia, systemic inflamma-tory response, disseminated intravascular coagulation (DIC), and intestinal bacterial translocation (Table 73-3).

Table 73-3 FACTORS IN THE PATHOGENESIS OF PANCREATITIS

Factor	Proposed Role in Pathogenesis
Pancreatic Enzymes
Trypsin	Perpetuation of proteolytic damage of pancreatic tissue (autodigestion)
	Perpetuation of activation of more trypsin and other proteases
	Consumption of plasma protease inhibitors
	Coagulation/fibrinolysis (DIC)
	Activation of kinin system and release of histamine from mast cells, contributing to edema and hemorrhage
Phospholipase A	Cell membrane damage (necrosis, non-cardiogenic pulmonary edema)
	Liberation of toxins (e.g., myocardial effects)
Elastase	Vascular damage (progression of edematous to hemorrhagic pancreatitis)
Chymotrypsin	Activation of xanthine oxidase (generation of oxygen-derived free radicals; see below)
Lipase	Local fat necrosis (peritonitis, “calcium soaps,” hypocalcemia)
Inflammatory Mediators	Systemic inflammatory response syndrome
	Vasodilation, hypotension, shock
	Local inflammation and aggregation of leukocytes; peritonitis
Oxygen-Derived Free Radicals	Damage of tissues by disrupting cell membranes through peroxidation of lipids in the membrane
	Endothelial cell injury (pancreatic edema and hemorrhage, DIC)
Coagulation/Fibrinolysis	Disseminated intravascular coagulopathy
	Thrombosis of pancreatic blood vessels
	Ischemic pancreatic necrosis

DIC, disseminated intravascular coagulation.

Key Point

Intrapancreatic activation of trypsin and other digestive enzymes leads to autodigestion of the pancreas. Impaired pancreatic microcirculation is a key factor in the progression from mild self-limiting pancreatitis to severe necrotizing pancreatitis.

• Natural protective mechanisms against autodigestion involve pancreatic secretory trypsin inhibitor, alpha₁-proteinase inhibitor, and alpha-macroglobulins. These become overwhelmed as pancreatitis develops.

• Pathologically, pancreatitis can be categorized as acute edematous, acute necrotizing, acute suppurative, or chronic nonsuppurative. Sequelae include pseudocyst, abscess, fibrosis, and atrophy.

Clinical Signs and Manifestations

Clinical signs of acute pancreatitis are extremely variable, ranging from inapparent to mild to fulminant “acute abdomen” crisis. Signs may be vague, especially in cats. In chronic pancreatitis, episodic signs may correspond to periodic flare-ups of inflammation. In some cases, clinical signs are dominated by secondary complications (e.g., DIC) or sequelae (e.g., diabetes mellitus).

Key Point

The “classic” signs of vomiting and abdominal pain are frequent in dogs with acute pancreatitis but are relatively uncommon in affected cats.

Canine Pancreatitis

Pancreatitis most frequently occurs in middle-aged and older dogs that are overweight. A recent history of dietary indiscretion or a high-fat meal is common.

• Vomiting (90% of severe cases), anorexia (91%), and depression are the most consistent signs.

• Cranial abdominal pain is found in 58% of dogs, varying from mild to intense (manifested as restlessness, panting, trembling, hunched-up abdomen, praying position of relief, seeking of cool surfaces, and pain on palpation).

• Cranial abdominal mass may be palpable in some dogs.

• Dehydration is detected in 50% of dogs.

• Diarrhea (sometimes hemorrhagic) is reported in 33% of dogs.

• Fever is seen in 32% of dogs, usually attributable to the inflammatory response. It does not necessarily imply infection.

• Weakness or, in severe cases, acute collapse from shock may be observed.

Feline Pancreatitis

Cats are more likely to have chronic “smoldering” pancreatitis, manifested by nonspecific signs of lethargy, anorexia, and weight loss, with or without vomiting. Cats with severe acute pancreatitis can have any of the clinical sign seen in dogs, but less consistently.

The reported frequency of clinical signs and physical findings in cats with severe pancreatitis is as follows:

• Lethargy (100% of cases)

• Inappetence (97%)

• Dehydration (92%)

• Hypothermia (68%)

• Icterus (64%)

• Vomiting (35%)

• Abdominal pain (25%)

• Palpable abdominal mass (23%)

• Dyspnea (20%)

• Diarrhea (15%)

• Ataxia (15%)

• Fever (7%)

Key Point

Concurrent inflammatory bowel disease and cholangitis are frequent in cats with pancreatitis. This may be related to the anatomic arrangement of the bile and pancreatic ducts that join and have a common opening into the duodenum in cats.

Acute Complications

Most of the following complications seriously worsen the prognosis in pancreatitis:

• Shock, collapse, and hypothermia (due to hypovolemia and endotoxemia)

• Peritonitis (sterile exudate) and intra-abdominal fat necrosis

• Jaundice (intrahepatic cholestasis, hepatocellular necrosis, biliary obstruction, lipidosis in cats)

• Hepatic lipidosis (in cats)

• Sepsis

• DIC (bleeding, thrombosis, infarction)

• Acute oliguric renal failure

• Intestinal hypomotility (ileus)

• Hypocalcemia (rarely, overt tetany)

• Hyperglycemia (due to hyperglucagonemia and hypoinsulinemia)

• Cardiac arrhythmias (myocardial depressant factors, myocardial ischemia or necrosis)

• Respiratory distress (rarely, non-cardiogenic pulmonary edema or pleural effusion)

Chronic Complications and Sequelae

• Pancreatic pseudocysts and abscesses—Characterized by persistence or recurrence of signs associated with a cavitated pancreatic mass that contains liquefied necrotic debris, which can be sterile (pseudocyst) or infected (abscess)

• Chronic relapsing pancreatitis—Characterized by chronic smoldering disease with periodic flare-ups

• End-stage pancreatic fibrosis and atrophy—Manifested as diabetes mellitus, exocrine pancreatic insufficiency, or both

• Liver disease—Resulting from common bile duct obstruction or concurrent cholangiohepatitis

Diagnosis

The diagnosis of pancreatitis is based on the combination of clinical signs, physical examination, routine laboratory findings, assays for circulating pancreatic enzymes, radiography, ultrasonography, and in some cases, pancreatic biopsy.

Clinical Signs and Physical Findings

• Suspect pancreatitis in animals presented for vomiting, depression, anorexia, and abdominal pain. Most dogs have vomiting, abdominal pain, or both; however, only 33% of cats have vomiting as a sign and only 25% are painful.

• Nearly 33% of dogs are febrile, compared with only 7% of cats. More than 66% of cats with severe acute pancreatitis are hypothermic.

• Identifiable risk factors increase the index of suspicion (e.g., obesity, recent fatty meal, miniature schnauzer breed, and endocrinopathy).

• A palpable right cranial abdominal mass or fluid suggests a pancreatic lesion.

Hematologic Findings

Dogs

• In dogs with severe pancreatitis, the most frequent findings are neutrophilic leukocytosis (55% of cases), with or without a left shift; thrombocytopenia (59%); and hemoconcentration (dehydration) or anemia (29%).

• Neutropenia with a degenerative left shift occurs occasionally with severe necrosis, peritonitis, sepsis, or endotoxemia.

• Red blood cell (RBC) fragments and macroplatelets are consistent with subclinical DIC.

Key Point

Evaluate hemostasis in pancreatitis dogs with thrombocytopenia that may be developing DIC.

Cats

• In cats with severe pancreatitis, the most frequent findings are anemia (55% of cases) or hemoconcentration (30%) and leukocytosis (30%) or leukopenia (15%).

Routine Serum Chemistries and Urinalysis

Several nonspecific abnormalities may be found on routine serum chemistries:

• Azotemia (increased blood urea nitrogen and creatinine), resulting frequently from dehydration and hypovolemia (prerenal) or occasionally from renal damage and acute oliguric renal failure

• Metabolic acidosis and hypokalemia

• Hypocalcemia (usually subclinical; tetany is rare)

Key Point

Hypokalemia is more common in cats with pancreatitis (50% of cases) than in dogs (5%) and is a negative prognostic indicator.

• Elevated serum liver enzymes (ALT, AST, ALP, GGT) and hyperbilirubinemia, can result from hepatocellular injury (due to ischemia, sepsis, or toxins from the pancreas), biliary obstruction, or concurrent cholangitis (cats).

• Hyperglycemia (usually transient, but some animals are diabetic after recovery)

• Fasting hyperlipemia (hypertriglyceridemia and hypercholesterolemia)

• Urinalysis is usually normal with concentrated specific gravity except in cases complicated by diabetes mellitus (glucosuria) or renal failure (isosthenuria).

Key Point

Because elevated levels of amylase, lipase, blood urea nitrogen, and creatinine are common in both renal failure and pancreatitis, assess urine specific gravity (USG) as a reflection of renal concentrating ability; USG > 1.025 indicates adequate renal function.

Serum Amylase and Lipase

Dogs

Serum amylase and lipase concentrations have traditionally been used as indicators of pancreatic inflammation, but these enzymes lack sensitivity and specificity and thus are only appropriate as aids for the diagnosis of canine pancreatitis. Amylase and lipase are normal in one-third to one-half of dogs with histologically confirmed pancreatitis, and up to one-half of dogs with elevation of one or both enzymes do not actually have pancreatitis. Serum amylase and lipase are frequently increased in non-pancreatic diseases.

• Serum amylase and lipase also originate from non-pancreatic sources and may be increased in many renal, gastrointestinal, liver, and neoplastic diseases.

• Delayed renal clearance of enzymes combined with increased secretion due to hypergastrinemia can cause elevations in azotemic patients.

• Corticosteroids in high doses can cause a significant increase (up to fivefold) in serum lipase in the absence of pancreatitis.

• The magnitude of amylase or lipase elevation does not correlate with the severity of the pancreatitis or the prognosis.

Cats

Serum amylase and lipase do not appear to be diagnostically useful in the cat. Most cats with pancreatitis often have minimal or no increase in amylase or lipase.

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