1. 
   

   What are the criteria for the diagnosis of acute pancreatitis?

   
   
2. 
   

   What efforts should be made to determine etiology during hospitalization, and what is the optimal timing of diagnostic and/or intervention studies in acute pancreatitis?

   
   
3. 
   

   What are the key components of early management?

   
   
4. 
   

   What is the management of late complications?

   
   
5. 
   

   When should consultation with gastroenterology, surgery, or interventional radiology be considered?

   
   
6. 
   

   When are specific interventions such as ERCP, fine-needle aspiration, or prophylactic antibiotics indicated?

Acute pancreatitis is a common cause for hospitalization in the United States. Recent data from the National Center for Health Statistics has indicated a rising frequency of admissions for acute pancreatitis attributed to the increase in gallstone-related disease. Annually, more than 300,000 hospital admissions for acute pancreatitis present in the United States at a direct cost of more than $2 billion. Although acute pancreatitis is typically a mild, self-limited disease, a wide range of severity exists. Fifteen to 20% of patients experience a more severe form of disease with overall inhospital mortality estimated to range between 3–5% of cases.

Risk factors for acute pancreatitis include both genetic susceptibility and environmental exposures. Genes involving mutation in the cystic fibrosis transmembrane conductance regulator (CFTR), cationic trypsinogen gene (PRSS1), and secretory trypsin inhibitor (SPINK1) have been identified in patients with recurrent acute pancreatitis. Other patient-related factors such as obesity have also been demonstrated to be associated with increased severity of disease.

The most common etiology for acute pancreatitis is now gallstone-related disease, followed by alcohol and post-ERCP (endoscopic retrograde cholangiopancreatography) pancreatitis (Table 156-1). Additional etiologies include metabolic derangements (hypercalcemia, hypertriglyceridemia) and medications (Table 156-2). Less common etiologies include autoimmune and hereditary forms of pancreatitis. Whether pancreas divisum itself is a cause for acute pancreatitis remains controversial.

Obstructive causes for pancreatitis secondary to pancreatic mass or cystic lesions, such as intraductal papillary mucinous neoplasm (IPMNs), are increasingly recognized due to improvements in imaging techniques.

Patients with acute pancreatitis usually complain of sudden onset unrelenting epigastric pain that is sharp in nature. This pain often radiates to the back. Nausea and vomiting are common as is anorexia. Patients may present with signs of volume depletion in the setting of decreased oral intake as well as potential third-space losses. Signs of systemic inflammation are common at the time of presentation including fever, tachycardia, and leukocytosis. Rarely, physical exam findings may include evidence of hemorrhagic pancreatitis such as flank (Grey-Turner sign) or periumbilical (Cullen sign) ecchymosis.

Acute pancreatitis results from local tissue injury to the pancreas. Ordinarily, digestive enzymes are sequestered in an inactivated form within vesicles (zymogen granules) of the acinar cell. However, in acute pancreatitis, an insult (alcohol, gallstones, medications, oxidative stress) leads to premature zymogen activation as well as retention of activated enzymes within the acinar cell. This leads to a process of auto-digestion that is associated with increased activation of the transcription factor NF-kb that in turn leads to increased release of proinflammatory cytokines (interleukins 1, 2, 6, 8 and TNF-alpha). This local inflammatory response leads to increased recruitment of neutrophils and macrophages. If left unchecked, this local inflammation can lead to systemic inflammation and subsequent multiorgan dysfunction syndrome (MODS). In patients with CFTR mutations, the decreased ductal secretion of chloride is believed to cause plugging in the secondary pancreatic ducts leading to acute pancreatic inflammation. In hereditary pancreatitis, an imbalance between acinar cell protective mechanisms results in the inability to inactivate a defective “supertrypsin” (PRSS1 mutation) or the presence of a defective trypsin inhibitor (SPINK1).

The presence of epigastric pain with an elevation in amylase/lipase ≥ 3 times normal is highly accurate for the diagnosis of acute pancreatitis. Additional considerations should include acute cholecystitis or ascending cholangitis (both of which may be concurrent with an attack of biliary pancreatitis). Less common considerations include a penetrating duodenal ulcer, renal colic or diabetic ketoacidosis. Further potentially life-threatening conditions include a perforated viscus, bowel obstruction or myocardial infarction. Serum amylase may also be elevated in salivary disorders, ectopic pregnancy or macroamylasemia.

The diagnosis of acute pancreatitis requires at least two of the following: (1) typical epigastric abdominal pain, (2) amylase/lipase evaluation ≥ 3 times upper limit of normal, and/or (3) confirmatory findings on cross-sectional imaging. Findings on abdominal ultrasound in conjunction with liver function tests have very high sensitivity for the detection of gallstone-related illness. Specifically, an elevated ALT level > 2 to 3 times normal has been found to have a 95% positive predictive value for gallstone-related illness. More recently, magnetic resonance cholangiopancreatography (MRCP) has emerged as a highly accurate, noninvasive means to evaluate for the presence of biliary pancreatitis (Figure 156-1).