recognition (i.e., damage/danger-associated pattern molecules and toll-like receptors (TLRs) as well as

the activation of transcription factors such as NF-κB play a role.8

The result of these events is pancreatic autodigestion, with injury to the vascular endothelium,

interstitium, and acinar cells. Increases in vascular permeability lead to interstitial edema.

Vasoconstriction, thrombosis, and capillary stasis can lead to ischemic (and perhaps ischemia–

reperfusion) injury and the development of pancreatic necrosis. With severe pancreatic injury, the

systemic inflammatory response syndrome (SIRS) and distant organ failure can occur. The systemic

complications are believed to be mediated by digestive enzymes and inflammatory mediators released

from the injured pancreas. For example, activated phospholipase A–induced digestion of lecithin (an

important component of pulmonary surfactant) may play a role in pathogenesis of acute respiratory

distress syndrome (ARDS) that occurs in the setting of acute pancreatitis. In addition, the circulatory

and inflammatory effects induced by acute pancreatitis are postulated to impair intestinal epithelial

barrier function, allowing for the translocation of bacteria from the intestinal lumen into the systemic

circulation. This phenomenon has been demonstrated to occur in animal models and may account for the

pathogenesis of pancreatic and peripancreatic infection that can complicate necrotizing pancreatitis.

ETIOLOGY

1 Although many etiologies of acute pancreatitis have been described, in the United States, more than

75% of cases are attributable to either gallstones or alcohol.

Gallstones

Gallstones cause approximately 35% of episodes of acute pancreatitis in the United States. In a

mechanistic model proposed over a century ago, a gallstone lodged at the papilla of Vater occludes the

ampullary orifice, leading to retrograde reflux of bile into the pancreatic duct through a common

channel shared by the common bile duct and the pancreatic duct (Fig. 53-2). Although elements of this

model have been challenged, the prevailing view is that transient or persistent obstruction of the

ampullary orifice by a gallstone or edema induced by stone passage is the inciting factor in the

pathogenesis of gallstone-induced pancreatitis. Microlithiasis refers to aggregates (<5 mm in diameter)

of cholesterol monohydrate crystals or calcium bilirubinate granules detected as “sludge” within the

gallbladder on ultrasonography or on examination of bile obtained during endoscopic retrograde

cholangiopancreatography (ERCP). An etiologic role for microlithiasis in acute pancreatitis remains

unproved; however, data derived from case-control studies suggest that cholecystectomy or endoscopic

sphincterotomy can reduce the risk of recurrent acute pancreatitis in patients with microlithiasis.

Figure 53-2. Illustration of the common channel concept. A gallstone lodged at the ampulla of Vater can cause reflux of bile into

the pancreatic duct.

Alcohol

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Ethanol causes approximately 40% of cases of acute pancreatitis in the United States. Most patients with

alcohol-induced acute pancreatitis also have underlying chronic pancreatitis. Potential mechanisms by

which alcohol-induced pancreatitis include sphincter of Oddi spasm, obstruction of small pancreatic

ductules by proteinaceous plugs, alcohol-induced metabolic abnormalities (e.g., hyperlipidemia), and

direct toxic effects induced by alcohol and its metabolites (e.g., acetaldehyde, acetate, and nonesterified

fatty acids).

Other Etiologies

A wide range of other etiologies of acute pancreatitis have been identified (Table 53-2). Ongoing

investigations are beginning to reveal specific gene abnormalities (e.g., mutations in cationic

trypsinogen PRSS1, pancreatic secretory trypsin inhibitor SPINK1, and the cystic fibrosis transmembrane

conductance regulator CFTR) that can be associated with pancreatitis. Patients for whom no etiology

can be identified despite thorough evaluation are classified as having idiopathic pancreatitis.

ETIOLOGY

Table 53-2 Etiology of Acute Pancreatitis

CLINICAL PRESENTATION

Abdominal pain, nausea, and vomiting are the most prevalent symptoms associated with acute

pancreatitis. The pain is visceral in quality, is localized to the epigastrium, often radiates to the back,

and may be alleviated with the patient leaning forward. Abdominal tenderness is the most prevalent

sign of acute pancreatitis. Tachycardia and hypotension may result from intravascular hypovolemia.

Low-grade fevers are common, but high-grade fevers are unusual in the absence of intra- or

extrapancreatic infection. Jaundice may be evident in the presence of cholangitis (e.g., with gallstoneinduced pancreatitis and persistent choledocholithiasis) or liver disease (alcohol-induced pancreatitis in

a patient with cirrhosis). Evidence of retroperitoneal hemorrhage may be become apparent if blood

dissects into the subcutaneous tissues of the flanks (Grey Turner sign), umbilicus (Cullen sign), or

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inguinal region (Fox sign); however, these findings are unusual. In approximately 20% of cases, acute

pancreatitis is associated with SIRS, hemodynamic lability, and/or organ failure (particularly

compromise of the cardiovascular, pulmonary, and renal systems) on presentation.

DIAGNOSIS

2 The differential diagnosis of acute pancreatitis includes other conditions causing acute upper

abdominal pain, such as biliary colic and cholecystitis, acute mesenteric ischemia, small bowel

obstruction, visceral perforation, and ruptured aortic aneurysm. Acute exacerbations of chronic

pancreatitis can also be associated with clinical features resembling those of acute pancreatitis. In

general, a diagnosis of acute pancreatitis can be made with the presence of two of the following three

features: (1) characteristic abdominal pain (acute onset of severe, persistent epigastric pain often

radiating to the back); (2) serum lipase (or amylase) levels at least three times greater than the upper

limit of normal; and (3) findings of acute pancreatitis on contrast-enhanced computed tomography (CT)

or magnetic resonance imaging (MRI).9,10 Imaging tests should be used selectively, to rule out other

diagnoses and for the indications discussed later. In cases of typical abdominal pain and confirmatory

laboratory tests, imaging is usually not needed at the time of admission.

Laboratory Tests

With pancreatic injury, a variety of digestive enzymes escape from acinar cells and enter the systemic

circulation. Of these enzymes, amylase is the most widely assayed to confirm the diagnosis of acute

pancreatitis. Amylase levels rise within several hours after onset of symptoms and typically remain

elevated for 3 to 5 days during uncomplicated episodes of mild acute pancreatitis. Because of the short

serum half-life of amylase (10 hours), levels can normalize as soon as 24 hours after disease onset. The

sensitivity of this test depends on what threshold value is used to define a positive result (90%

sensitivity with a threshold value just above the normal range vs. 60% sensitivity with a threshold value

at three times the upper limit of normal). Specificity (which also varies with the threshold values

selected) is limited because a wide range of disorders can cause elevations in serum amylase

concentration. Assays that detect increases in the serum concentration of amylase of pancreatic origin

(P-isoamylase) alone are associated with greater specificity. Increased urinary amylase concentrations

and amylase-to-creatinine clearance ratios occur with acute pancreatitis; however, these parameters

offer no advantage over serum amylase concentrations, except in the evaluation of macroamylasemia

(in which urinary amylase excretion is not increased despite elevations in serum amylase

concentration).

Serum lipase concentrations increase with kinetics similar to those of amylase. It has a longer serum

half-life than amylase, however, and may be useful for diagnosing acute pancreatitis late in the course

of an episode (at which time serum amylase concentrations may have already normalized). Although

lipase is more specific than amylase in the diagnosis of acute pancreatitis, note that lipase is produced at

a range of nonpancreatic sites, including the intestine, liver, biliary tract, and stomach, and tongue.

The magnitude of the increases in amylase or lipase concentrations has no correlation with severity of

pancreatitis. In general, the magnitude of increases in amylase concentrations tends to be greater in

patients with gallstone pancreatitis than in those with alcohol-induced pancreatitis; however, this

finding is unreliable in distinguishing between these two etiologies.

Imaging Tests

Findings on plain radiographs associated with acute pancreatitis are nonspecific and include ileus that

may be generalized or localized to a segment of small intestine (“sentinel loop”) or transverse colon

(“colon cut-off sign”), psoas muscle margins that are obscured by retroperitoneal edema, an elevated

hemidiaphragm, pleural effusions, and basilar atelectasis.

Ultrasonography may reveal a diffusely enlarged, hypoechoic pancreas. However, overlying bowel

gas (particularly prominent with ileus) limits visualization of the pancreas in a large percentage of

cases. Although ultrasonography has poor sensitivity in the diagnosis of acute pancreatitis, it plays an

important role in the identification of the etiology of pancreatitis (e.g., the detection of gallstones).

CT scanning is the most important imaging test in the evaluation of acute pancreatitis. CT findings of

mild acute pancreatitis include pancreatic enlargement and edema, effacement of the normal lobulated

contour of the pancreas, and stranding of peripancreatic fat (Fig. 53-3). In addition, dynamic CT

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scanning performed after the bolus administration of intravenous contrast can demonstrate regions of

pancreas that have poor or no perfusion, as seen with pancreatic necrosis (Fig. 53-4). Detection of

necrosis plays an important role in assessment of disease severity, as discussed further later. CT can also

characterize collections and other complications associated with acute pancreatitis.

Figure 53-3. Computed tomography scan of acute interstitial pancreatitis.

Figure 53-4. Computed tomography scan of acute necrotizing pancreatitis.

MRI and magnetic resonance cholangiopancreatography (MRCP) are being used with increasing

frequency in patients with acute pancreatitis. These examinations have the potential to offer better

definition of pancreatic and biliary ductal abnormalities than CT scanning, and they are applicable in

patients for whom ionizing radiation or iodinated intravenous contrast agents used in CT scanning are

contraindicated. MRI can suggest the presence of pancreatic necrosis even without the use of

intravenous gadolinium. MRI also has the advantage of better characterizing collections associated with

acute pancreatitis, in particular with respect to differentiating solid from liquid components.

Disadvantages of MRI include high cost, limited availability, and the long duration of examinations.

ASSESSMENT OF DISEASE SEVERITY

3 Approximately 80% of cases of acute pancreatitis are mild, associated with minimal systemic

derangements, and generally resolve within 5 to 7 days, even with minimal therapy. The mortality rate

associated with mild acute pancreatitis is less than 1%.

4, 5 Approximately 20% of cases are associated with either organ failure or the development of local

complications. The mortality rate for these patients ranges from approximately 10% to 20% in

contemporary series.11–14 One-half of deaths occur within the first 2 weeks after the onset of symptoms;

these deaths are primarily the result of SIRS-induced multisystem organ failure. Most of the remaining

deaths occur beyond 2 weeks after presentation and result from complications of pancreatic necrosis,

especially infection.

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