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Chapter 53

Acute Pancreatitis

Jason S. Gold and Edward E. Whang

Key Points

1 In the United States, more than 75% of cases of acute pancreatitis are attributable to either

gallstones or alcohol.

2 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 CT or MRI.

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 minimaltherapy.

4 Severe acute pancreatitis accounts for about 20% of cases and is defined as acute pancreatitis

associated with one or more of the following: pancreatic necrosis, distant organ failure, and the

development of local complications such as hemorrhage, abscess, or pseudocyst.

5 The mortality rate associated with severe acute pancreatitis ranges from 10% to 20%, with half of

the deaths in the first 2 weeks as the result of SIRS-induced multisystem organ failure and the

remaining occurring later as the result of pancreatic necrosis/infection.

6 The most important component of initial management of acute pancreatitis is fluid resuscitation.

7 Early ERCP in acute pancreatitis has been subjected to extensive study. Early ERCP with stone

extraction and sphincterotomy clearly benefits the subset of patients with gallstone pancreatitis who

have cholangitis.

8 Infection of pancreatic and peripancreatic necrosis complicates 30% to 70% of cases of acute

necrotizing pancreatitis and most commonly becomes established during the second to third weeks

after onset of disease.

9 Infected necrosis is suggested by clinical signs such as persistent fever, increasing leukocytosis, and

imaging findings such as gas in peripancreatic collections. When the necessary, infected necrosis can

be confirmed by CT-guided fine needle aspiration.

10 Invasive intervention is usually indicated in the presence of infected necrosis. In contrast, sterile

necrotic collections almost never require intervention in the acute phase of necrotizing pancreatitis.

11 Procedures for the treatment of infected necrosis are best performed when collections become

walled off and demarcated from viable pancreatic tissue with at least partial liquefaction, which

typically requires a delay of 4 to 6 weeks after disease onset.

12 Drainage alone is now the initial recommended intervention for infected pancreatic necrosis. This is

most often accomplished through a percutaneous image-guided approach. When percutaneous drains

are placed, preference should be given to a retroperitoneal approach. Drainage can also be

accomplished through an endoscopic transluminal approach.

13 When required, débridement can often be performed through minimally invasive techniques.

14 Current well-accepted indications for intervention on pseudocysts and walled-off necrosis in the

absence of infection include the presence of symptoms attributable to the collection such as

intractable pain or obstruction of the stomach, duodenum or bile duct.

15 There are multiple treatment options available for the treatment of pancreatic pseudocysts and

sterile walled-off necrosis, including percutaneous aspiration, percutaneous drainage, and internal

drainage (performed transabdominally or endoscopically).

Acute pancreatitis is an acute inflammatory process of the pancreas with variable involvement of other

regional tissues or remote organ systems.1 In the United States, more than 250,000 patients are

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hospitalized annually with acute pancreatitis as the primary diagnosis. It is the principal cause of

approximately 3,000 deaths per year and a contributing factor in an additional 2,500 deaths. The direct

cost attributable to acute pancreatitis exceeds $2.5 billion per year in the United States.2

CLASSIFICATION AND DEFINITIONS

A useful system for defining and classifying acute pancreatitis and its complications was recently

developed through an iterative process involving several national and international pancreas

organizations.3 This new system is a modification of widely accepted but outdated classification system

originally derived from a multidisciplinary symposium held in 1992.1 The clinically based definitions

reached by consensus are shown in Table 53-1.

PATHOLOGY AND PATHOPHYSIOLOGY

The typical pathologic correlate of mild acute pancreatitis is interstitial edematous pancreatitis, in which

the pancreatic parenchyma is edematous and infiltrated with inflammatory cells. Gross architectural

features are preserved. In contrast, in necrotizing pancreatitis variable amounts of pancreatic parenchyma

and peripancreatic fat have undergone tissue necrosis, with vascular inflammation and thrombosis being

prominent features.

Studies using experimental models suggest that prototypical molecular and cellular derangements lead

to pancreatic injury, regardless of the specific etiology or inciting event that triggers an episode of acute

pancreatitis. Among the earliest of these derangements appears to be abnormal activation of proteolytic

enzymes within pancreatic acinar cells.4 Under normal conditions, trypsinogen and other digestive

zymogens are stored in granules that are segregated from lysosomal enzymes (e.g., cathepsin B) and

acid. Early in the course of acute pancreatitis, cytoplasmic vacuoles containing activated proteolytic

enzymes appear. How the digestive enzymes are activated, and what role these vacuoles play has been

the subject of much investigation. In the prevailing model, trypsinogen is believed to be activated to

yield trypsin either by colocalization with the lysosomal hydrolase cathepsin B5 or through

autoactivation due to a moderately acidic pH6. It has been noted that the cytoplasmic vacuoles

appearing in the acinar cell in experimental acute pancreatitis share expression of proteins with

autophagosomes. Autophagosomes are vacuoles that degrade cellular components such as organelles in

the process of autophagy. Highlighting the possible importance of autophagy in the development of

pancreatitis, mice lacking expression of the autophagy-related gene Atg5 in the pancreas fail to exhibit

prototypical features of acute pancreatitis.7

CLASSIFICATION

Table 53-1 Terms Used in the Classification of Acute Pancreatitis

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Figure 53-1. Schematic diagram depicting activation of proteolytic enzymes, possibly through colocalization of zymogen granules

and lysosomes, and subsequent rupture of zymogen granules releasing the activated enzymes into the cytoplasm of the pancreatic

acinar cell. The activated enzymes then undergo disordered basolateral discharge from the acinar cell into the pancreatic

parenchyma.

Acinar cell injury induced by active trypsin allows it to be released into the pancreatic parenchyma

(Fig. 53-1) where it activates more trypsin and other digestive enzymes (e.g., chymotrypsin,

phospholipase, and elastase). Trypsin can also activate the complement, kallikrein-kinin, coagulation,

and fibrinolysis cascades within the pancreatic parenchyma. Activation of these enzymes is believed to

initiate a vicious cycle in which activated enzymes cause cellular injury, an event that leads to the

release of even more destructive enzymes. This cycle can overwhelm defense mechanisms that normally

serve to limit the injurious consequences of premature trypsin activation within the pancreas (e.g.,

pancreatic secretory trypsin inhibitor–mediated inhibition of trypsin activity).

An inflammatory response is then generated in response to the initial acinar cell injury. This

inflammatory response is marked by the infiltration of the pancreatic parenchyma with immune cells

such as neutrophils, macrophages, monocytes, and lymphocytes and the release of a broad range of

proinflammatory mediators such as tumor necrosis factor (TNF) α; interleukins (IL) 1β, 6, and 8;

platelet-activating factor; chemokines (i.e., CXCL2 and CCL2); prostaglandins; and leukotrienes. The

inflammatory response, to a large extent, determines the severity of pancreatitis, and the blockade of

several components of the inflammatory response ameliorates the disease and reduces mortality in

experimental models. The understanding of how the initial acinar cell injury provokes an inflammatory

response is incomplete, but it appears that reactive oxygen species (ROS) and innate molecular pattern

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