Acute pancreatitis is a clinical syndrome resulting from the escape of activated pancreatic digestive enzymes from the duct system into the parenchyma. It is associated with extensive destruction of pancreatic and peripancreatic tissue and acute inflammation.
Acute pancreatitis is a common and important medical emergency, accounting for about one in every 500 admissions to general hospital emergency rooms.
In about 25% of cases of acute pancreatitis, no etiologic factor can be identified. Infectious agents are usually not involved, although mild nonnecrotizing acute pancreatitis occurs in association with some viral diseases—commonly mumps and cytomegalovirus infection.
Factors associated with acute pancreatitis are shown in Figure 45-2 and discussed briefly below.
Acute pancreatitis—etiologic factors, mechanisms, pathologic changes, and clinical effects.
Biliary tract calculi are present in about 50% of cases and may obstruct the terminal bile duct. Reflux of bile or infected duodenal contents into the pancreatic duct has been suggested as a mechanism leading to pancreatitis in bile duct disease. Obstruction of the pancreatic duct may occur when a calculus becomes lodged in the ampulla of Vater. Acute pancreatitis complicating gallstones is chiefly a disorder of women because of the female preponderance of gallstone disease.
Alcoholism as a cause of acute pancreatitis occurs with varying frequency in different parts of the world. It is common in the United States, being involved in 65% of cases of acute pancreatitis; in Europe, the incidence is 5–20%. Acute pancreatitis commonly occurs after a bout of heavy drinking. A direct toxic effect of alcohol on pancreatic acinar cells has been postulated.
Hypercalcemia, as occurs in primary hyperparathyroidism, is complicated by acute pancreatitis in about 10% of cases. A high plasma calcium concentration is thought to stimulate activation of trypsinogen in the pancreatic duct.
The hyperlipidemias—particularly those types associated with increased plasma levels of chylomicrons—are complicated by acute pancreatitis. It is postulated that free fatty acids liberated by the action of pancreatic lipase produce acinar injury.
In shock and hypothermia, decreased perfusion of the pancreas may lead to cellular degeneration, release of pancreatic enzymes, and acute pancreatitis.
Thiazide diuretics, corticosteroids, anticancer agents, and other drugs may also cause acute pancreatitis. Radiation to the retroperitoneum for treatment of malignant neoplasms is an uncommon cause of acute pancreatitis.
The pathologic changes in acute pancreatitis are the result of the action of pancreatic enzymes on the pancreas and surrounding tissues (Figure 45-3). Trypsin and chymotrypsin activate phospholipase and elastase as well as kinins, complement, the coagulation cascade, and plasmin, leading to acute inflammation, thrombosis, and hemorrhage. Elastase contributes to vascular injury. Phospholipases act on cell membranes, causing cell injury. Pancreatic lipase acts on surrounding adipose tissue, causing enzymatic fat necrosis (see Chapter 1: Cell Degeneration & Necrosis).
Acute pancreatitis, showing marked hemorrhagic necrosis in the upper retroperitoneum around the pancreas.
In addition to a local action, pancreatic enzymes enter the bloodstream. Circulating amylase does not contribute to cell injury; however, phospholipases are thought to contribute to the production of adult respiratory distress syndrome by interfering with the normal function of pulmonary surfactant. Rarely, high serum lipase levels are associated with fat necrosis at sites distant from the pancreas.
Acute pancreatitis is characterized by widespread necrosis in tissues subjected to the effect of extravasated pancreatic enzymes. Necrosis of pancreatic parenchyma is initially coagulative but the necrotic cells rapidly undergo liquefaction. Vascular necrosis and disruption result in hemorrhage. Fat necrosis appears as chalky white foci that may be calcified, usually in and around the pancreas, omentum, and mesentery (Figure 45-3). Rarely, fat necrosis extends down the retroperitoneum and into the mediastinum. In severe cases, massive liquefactive necrosis of the pancreas occurs, resulting in a pancreatic abscess.
In very severe cases, death may occur before an adequate inflammatory response can be mobilized. Neutrophils predominate when the inflammation becomes established.
The peritoneal cavity sometimes contains a brownish serous fluid (pancreatic ascites). This fluid contains altered blood, fat globules (“chicken broth”), and very high levels of amylase.
Acute pancreatitis usually presents as a medical emergency. Patients develop severe constant epigastric pain, frequently referred to the back, accompanied by vomiting and shock. Shock is caused by peripheral circulatory failure resulting from hemorrhage and the entry of kinins into the bloodstream (Figure 45-2). Mild jaundice may be present. In severe pancreatitis, there is discoloration due to hemorrhage in the subcutaneous tissue around the umbilicus (Cullen's sign) and in the flanks (Turner's sign). Activation of the plasma coagulation cascade may lead to disseminated intravascular coagulation.
There is an almost immediate (within hours) elevation of the serum amylase, often to 10–20 times the normal upper level; amylase levels return to normal in 2–3 days. Serum lipase is increased later, usually after 72 hours. Hypocalcemia is present in severe cases and is a bad prognostic sign. Transient glycosuria is present in the acute stage in about 10% of cases as a result of islet dysfunction. Permanent diabetes mellitus almost never follows a single attack of acute pancreatitis.
Most patients recover from the acute attack with proper supportive care, and the pancreas regenerates and returns almost to normal, with mild residual scarring. In severe cases, death may occur in the acute phase as a consequence of pancreatic abscess, severe hemorrhage, shock, disseminated intravascular coagulation, or respiratory distress syndrome.
Pancreatic pseudocyst (see below) may follow weeks to months after recovery from an acute attack.
Chronic pancreatitis is a chronic disease characterized by progressive destruction of the parenchyma with chronic inflammation, fibrosis, stenosis and dilation of the duct system, and eventually impairment of pancreatic function.
Chronic alcoholism and biliary tract calculi are the two main conditions that are associated with chronic pancreatitis. In the United States, alcoholism is believed to be implicated in about 40% of cases and biliary tract disease in 20%. In 30–40% of cases, no etiologic factors are identified. Some cases follow recurrent acute episodes; cystic fibrosis is a specific type of chronic pancreatitis described earlier.
Chronic pancreatitis—etiologic factors, pathologic changes, and clinical effects.
Chronic pancreatitis is characterized by shrinkage of the pancreas as a result of fibrosis and atrophy of acinar structures. The changes usually involve the gland diffusely; more rarely, a firm, localized mass forms that is difficult to distinguish grossly from carcinoma.
The pancreatic ducts show multiple areas of stenosis with irregular dilation distally. Ducts are filled with inspissated secretions that may undergo calcification to form calculi (Figure 45-5). Diffuse calcification imparts a rock-hard consistency to the gland.
Chronic pancreatitis, showing markedly dilated ducts containing calculi. The pancreatic parenchyma between the ducts has undergone marked atrophy and fibrous contraction.
Microscopically, there is acinar loss with marked fibrosis. At the end stage there are almost no recognizable acini, and the gland is composed of dilated ducts separated by collagen. Islets tend to withstand destruction better than acini. A variable lymphocytic infiltrate is present.
Pain is the dominant symptom. It may be constant or intermittent and can be so severe as to lead to narcotic dependence. In many cases, pain is associated with acute exacerbations, and the patients are asymptomatic between relapses. When pain is caused by dilation of the duct system, surgical correction by draining the dilated duct system may provide relief.
Pancreatic exocrine insufficiency due to failure of secretion of pancreatic juice leads to steatorrhea, malabsorption of fat-soluble vitamins, and weight loss. Endocrine insufficiency (diabetes mellitus) occurs in about 30% of cases.
The course is variable. Many patients have recurrent attacks of severe pain, vomiting, and elevation of serum amylase, due probably to repeated acute episodes (chronic relapsing pancreatitis). Acute attacks may be followed by formation of pancreatic pseudocysts (see below).
In about 5% of patients with severe sclerosing chronic pancreatitis affecting the head of the pancreas, obstruction of the common bile duct leads to deep jaundice. This condition is difficult to differentiate from jaundice due to pancreatic carcinoma.
The diagnosis of chronic pancreatitis is made on clinical grounds. There are no specific laboratory tests, but the presence of calcification on x-ray provides supportive evidence. In chronic disease, the amount of residual pancreatic tissue may be insufficient to cause elevation of serum amylase.
Treatment of chronic pancreatitis consists of management of the pain, malabsorption, and diabetes. When pain cannot be controlled by drugs, surgery to drain the pancreatic duct (by creating an opening between the duct and a loop of jejunum, ie, pancreaticojejunostomy) often has good results. Malabsorption and diabetes mellitus can be controlled by dietary supplements and insulin if necessary. The complications of diabetes mellitus represent the main threat to life.