Acute pancreatitis is a reversible inflammatory disorder that varies in severity, from focal edema and fat necrosis to widespread hemorrhagic necrosis. This is a relatively common condition, with an annual incidence of 10 to 20 per 100,000 people in the Western world.
The most common cause of acute pancreatitis in the United States is the impaction of gallstones within the common bile duct, impeding the flow of pancreatic enzymes through the ampulla of Vater (“gallstone pancreatitis”); this is closely followed by pancreatitis secondary to excessive alcohol intake. Overall, gallstones and alcoholism account for greater than 80% of acute pancreatitis cases, with the remaining caused by a multitude of factors (
Table 17.1 ). These include the following:
Non–gallstone-related obstruction of the pancreatic ducts (e.g., due to pancreatic cancer or other periampullary neoplasms, pancreas divisum, biliary “sludge,” or parasites, particularly Ascaris lumbricoides and Clonorchis sinensis)
Medications including anti-convulsants, cancer chemotherapeutic agents, thiazide diuretics, estrogens, and more than 85 others in clinical use
Infections with mumps virus or coxsackievirus, which can directly infect pancreatic exocrine cells
Metabolic disorders, including hypertriglyceridemia, hyperparathyroidism, and other hypercalcemic states http://ebooksmedicine.net
Table 17.1 Etiologic Factors in Acute Pancreatitis
HyperlipoproteinemiaHypercalcemiaDrugs(e.g.,azathioprine) *MostcommoncausesintheUnitedStates.
Ischemia due to vascular thrombosis, embolism, vasculitis, or shock
Trauma, both blunt force and iatrogenic during surgery or endoscopy
Germline mutations involving genes encoding pancreatic enzymes or their inhibitors. For example, hereditary pancreatitis is a rare autosomal dominant disease with 80% penetrance that is characterized by recurrent attacks of severe pancreatitis, usually beginning in childhood. It is caused by mutations in the PRSS1 gene, which encodes trypsinogen, the proenzyme of pancreatic trypsin. The pathogenic mutations alter the site through which trypsin cleaves and inactivates itself, abrogating an important negative feedback mechanism. This defect leads not only to the hyperactivation of trypsin, but also to the hyperactivation of many other digestive enzymes that require trypsin cleavage for their activation. As a result of this unbridled protease activity, the pancreas is prone to autodigestion and injury. Loss-of-function mutations in genes that encode protease inhibitors such as SPINK1 are less commonly associated with hereditary pancreatitis.
Of note, 10% to 20% of cases of acute pancreatitis have no identifiable cause (idiopathic pancreatitis), although a growing body of evidence suggests that many may have an underlying genetic basis. For example, a subset of these so-called idiopathic pancreatitis patients has underlying germ line mutations of the CFTR gene with symptoms predominantly restricted to the pancreas (Chapter 7).