In the United States, acute pancreatitis is the most common reason for hospitalization due to a gastrointestinal illness, with over 200 000 patients admitted annually. The vast majority of patients have mild interstitial pancreatitis, which is usually self‐limiting with minimal morbidity and no mortality. However, approximately 30% of patients will develop moderately severe or severe pancreatitis with organ failure, localized complications, and occasionally death. The two most common risk factors for acute pancreatitis are gallstone disease and excessive alcohol use. However, there are multiple other reasons for patients to develop acute pancreatitis (Table 38.1).

Microscopically, patients with severe acute pancreatitis (SAP) develop extensive necrosis along with diffuse hemorrhage of the entire gland, while interstitial edema and infiltration of immune cells together with fat necrosis inside and outside the pancreas define the typical features of mild acute pancreatitis (Figure 38.1). Multiple organ failure in SAP is a consequence of the systemic activation of the immune system, known as systemic inflammatory response syndrome (SIRS). Major and early complications during SAP include acute lung injury, and kidney and hemodynamic failure. The pathophysiology of SAP with multiple organ failure is poorly understood.

In an attempt to identify predictors of complicated acute pancreatitis, several association studies linking cytokines and chemokines with acute pancreatitis severity have been conducted. These identified serum levels of interleukin (IL)‐6 and the IL‐6‐dependent acute phase protein C‐reactive protein (CRP) as the most reliable parameters for SAP. Recent findings suggest that IL‐6 is not only a predictor of SAP but plays a significant role in its pathogenesis. Activation of transcription factors such as nuclear factor‐κB (NF‐κB) and Stat3 results in production of factors that promote distant organ failure. While excessive stimulation of the immune system (hyperinflammatory status, SIRS) accounts for the early systemic complications, compensatory antiinflammatory response syndrome (CARS) contributes to the local and septic problems in the late phase (Figures 38.2 and 38.3).

Successful management of pancreatitis depends on prediction of disease severity and the identification of patients who are at risk for local and systemic complications. Recognized markers of the risk of SAP include new scoring systems such as the Bedside Index of Severity of Acute Pancreatitis (BISAP) or single parameters, including elevated blood glucose, blood urea nitrogen (BUN), and hematocrit (Tables 38.2 and 38.3, Box 38.1). Among values that measure SIRS, CRP, IL‐6, and its soluble IL‐6 receptor were reliably linked to SAP. Agitation, confusion, hypoxemia, and lack of improvement within 48 h are signs suggesting deterioration. Patients older than 55 years are also at higher risk of undergoing a severe inflammation of the pancreas, as are obese patients with a body mass index greater than 30.

A diagnostic algorithm for acute pancreatitis is shown is demonstrated in Figure 38.4. Diagnosis is based on classic history and physical exam findings, elevation in serum amylase and/or lipase levels greater than three times the upper limit of normal, and/or cross‐sectional imaging demonstrating inflammatory changes within the pancreas.

The most common risk factors for acute pancreatitis in adults are gallbladder disease (usually due to concomitant choledocholithiasis) and chronic or excessive alcohol consumption. Other important causes include hypertriglyceridemia, drugs (e.g., azathioprine, thiazide, estrogens), trauma from endoscopic retrograde cholangiopancreatography (ERCP), hypercalcemia, abdominal trauma, various infections, ischemia, and hereditary causes (see Table 38.1). In about 15% of patients the cause remains unknown after thorough investigation, although this should become less common as factors of genetic predisposition, environmental susceptibility, and autoimmunity are elucidated.

Autoimmune pancreatitis (AIP) has become an important differential diagnostic consideration in patients with otherwise unexplained recurrent inflammation of the gland. First reported by Sarles et al. in 1961, the term “autoimmune pancreatitis” was coined for a steroid‐responsive, mass‐forming pancreatitis associated with increased g‐globulin (hypergammaglobulin) or g‐globulin 4 (IgG4) and elevated autoantibody titers (Figures 38.5 and 38.6).

Causes of acute pancreatitis
Obstruction	Bile duct stones including microlithiasis, pancreatic or biliary tumor, pancreatic anomalies (pancreas divisum, annular pancreas, choledochocele), sphincter of Oddi dysfunction, periampullary duodenal diverticulae
Toxins	Alcohol, scorpion bite (Tityus trinitatis), organophosphate
Genetics	PRSS1, SPINK1, CFTR, CTRC, CASR
Infections	Bacterial (e.g., Mycoplasma, Legionella, Leptospira, Salmonella), viral (e.g., mumps, coxsackie, hepatitis B, cytomegalovirus, varicella zoster, herpes), or parasitic (e.g., Ascaris, Cryptosporidium, Toxoplasma) infections
Medical interventions	ERCP, postoperative, coronary bypass and abdominal surgery, colonoscopy, pancreatic biopsy
Metabolism	Hypercalcemia, hyperlipidemia
Drugs	Class I–IV drugs
Autoimmune syndrome	Autoimmune pancreatitis type II, systemic lupus erythematosus, Sjögren syndrome
Others	Trauma, ischemia, pregnancy, idiopathic, steatosis

Parameter	Score
BUN >25–mg/dL	1
Impaired mental status	1
SIRS	1
Age >60 years	1
Pleural effusion	1
BISAP score	Mortality (%)
0	0.2
1	0.6
2	2
3	5–8
4	13–19
5	22–27

Parameters/scores	Form of pancreatitis
HAP score	Mild
Hematocrit >44%	Severe
Serum glucose >125 mg/dL	Severe
BUN >22 mg/dL	Severe
APACHE II score ≥8	Severe
Ranson/BISAP score >3	Severe
CRP >15 mg/dL	Severe

named types 1 and 2 (Table 38.4); lymphoplasmacytic sclerosing pancreatitis is the histological pattern seen in type 1 (Figures 38.7 and 38.8) and idiopathic duct centric pancreatitis is the histological pattern seen in type 2 (Figure 38.9). While both types can affect other organs, type 1 is typically a multiorgan disease in which the pancreas is only one of the many organs affected, the pancreatic affliction being called AIP.

Diffuse enlargement of the pancreas and effacement of the lobular contour of the pancreas in imaging of the pancreas, the so‐called “sausage‐like” appearance, is a typical finding in AIP. As fibroinflammatory changes involve the peripancreatic adipose tissue, a capsule‐like rim surrounding the pancreas is specifically detected in some AIP patients. Although typical features of AIP (narrow stricture of more than one‐third the length of the pancreatic duct, lack of upstream dilation from the stricture, multiple strictures, side branches arising from the stricture site) have been defined by ERCP, its role in the diagnostic algorithm is uncertain. Corticosteroids are the treatment of choice in the acute flair of AIP1 and AIP 2 (Figure 38.10).

Pancreas divisum is the most common congenital anatomical variation of the pancreatic ductal anatomy and occurs in approximately 10% of the population (Figures 38.11 and 38.12). The normal pancreas develops from the fusion of dorsal and ventral pancreatic buds during fetal development. In up to 90% of individuals, the ducts of both the dorsal and ventral buds fuse along with the parenchymal fusion, resulting in the main pancreatic duct draining the whole pancreas via the major papilla. In pancreas divisum, the fusion of dorsal and ventral pancreatic buds does not occur and the dorsal duct drains the majority of the pancreas via the minor papilla and the ventral duct drains only a small proportion of the pancreas (inferior portion of the head) via the major papilla. There are both complete and incomplete variants of pancreas divisum. The most likely mechanism for this is the presence of a small and stenotic minor papilla orifice in some individuals. This leads on to high dorsal ductal pressure during active secretion, resulting in inadequate drainage and ductal distension. This presumably causes recurrent acute pancreatitis, chronic pancreatitis, and pancreatic type abdominal pain without biochemical or radiological evidence of pancreatitis, especially in conjunction with a hereditary cause of pancreatitis such as a CFTR mutation. There are also certain abnormalities in the region of the ampulla – such as diverticula – which can predispose patients to recurrent pancreatitis (Figure 38.13).

A similar mechanism is proposed for patients with recurrent acute pancreatitis and sphincter of Oddi dysfunction (SOD). ERCP with manometry has been recommended to exclude SOD; a basal pressure of 40 mmHg or greater sustained for at least 30 seconds is considered abnormal. A number of studies suggest a prevalence rate for SOD of 30–45% in unexplained acute pancreatitis, making it the most common cause of pancreatitis identified in this group. Therapy of SOD is biliary sphincterotomy or a combination of biliary and pancreatic sphincterotomy.

Patients with SOD are at high risk for development of acute pancreatitis after ERCP. This type of acute pancreatitis is called post‐ERCP pancreatitis. The incidence of acute pancreatitis associated with therapeutic ERCP is 1.6–5.4% (mild approximately 2.3%, moderate approximately 2.8%, severe approximately 0.4%). While diagnostic ERCP is continuously replaced by magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS), therapeutic ERCP has still an important role in pancreatic (Figure 38.14) and biliary diseases. Further important risk factors for ERCP‐associated acute pancreatitis include female gender, past history of post‐ERCP pancreatitis, precut, difficult cannulation, endoscopic papillary balloon dilation, and performance of pancreaticography (see Figure 38.14).

The diagnosis of acute pancreatitis is primarily based on at least two of the following criteria: (1) acute abdominal pain; (2) evidence of elevation of lipase and/or amylase in the serum at least three times greater than the upper limit of normal; and (3) characteristic findings of acute pancreatitis on transabdominal ultrasonography or contrast‐enhanced computed tomography (CECT) and, less commonly, magnetic resonance imaging (MRI).

The cardinal symptom of abdominal pain is present in about 95% of patients and typically radiates in a band‐like manner to the lower thoracic region of the back. The pain tends to be steady but is exacerbated by eating or drinking. With biliary pancreatitis, the pain may be more localized to the right upper quadrant and more variable in intensity over time because of the contribution of biliary colic.

Cullen’s and Turner’s signs have long been known to be associated with retroperitoneal bleeding and indicate SAP. Cullen’s sign arises from the spread of retroperitoneal blood into the falciform ligament and subsequently to subcutaneous umbilical tissues through the connective tissue covering of the round ligament. In contrast, Turner’s sign is produced by hemorrhagic fluid spreading from the posterior pararenal space to the lateral edge of the quadratus lumborum muscle and thereafter to the subcutaneous tissues by means of a defect in the fascia of the flank.

Abdominal compartment syndrome is defined as an increase of intraabdominal pressure of more than 20 mmHg, which is associated with occurrence of organ failure (Figures 38.15 and 38.16). The incidence of abdominal compartment syndrome among patients with SAP ranges from 23% to 56%. The mechanisms involved in the development of abdominal compartment syndrome include increased capillary permeability, hypoalbuminemia, and volume overload, which produce a large retroperitoneal and visceral edema. Surgical decompression by midline laparotomy provides the most effective treatment of this complication.

Serum amylase generally rises within a few hours after the onset of symptoms and returns to normal within 3–5 days. In some patients, amylase activity is still normal on admission. Thus, when serum amylase concentration is high and clinical presentation is not consistent with acute pancreatitis, nonpancreatic causes of hyperamylasemia should be examined. In patients with acute pancreatitis, serum lipase remains elevated for a longer period of time than amylase, which can be helpful in patients with delayed presentation. Furthermore, lipase is more pancreas specific than amylase. The biochemical markers of a biliary etiology of acute pancreatitis include an alanine aminotransferase elevation of more than three times the upper range of normal and a serum total bilirubin greater than 3 mg%. In such cases, transabdominal ultrasound, EUS, or MRCP can be helpful in confirming retained stones in the bile duct (Figure 38.17).

Imaging is frequently recommended to confirm the clinical diagnosis, ascertain the cause, and grade the extent and severity of acute pancreatitis. Radiography, upper gastrointestinal series, and ultrasound are of limited value in the diagnosis of acute pancreatitis. In one‐third of patients, chest radiography shows abnormalities such as elevation of one hemidiaphragm and pleural effusions, pulmonary infiltrates, or both (Figure 38.18). On abdominal ultrasound, bowel gases often mask focal hypoechoic areas within the pancreas. Abdominal ultrasound is helpful in detecting cholelithiasis and biliary obstruction. Unlike EUS, the sensitivity of abdominal ultrasound in detecting biliary sludge or choledocholithiasis is very low.

Assessment for potential of gallstone‐induced acute pancreatitis should be given top priority because of its management implications. ERCP/sphincterotomy should be performed immediately (within 24 h) in patients with gallstone‐induced acute pancreatitis, if a complication of cholangitis is present or suspected (Figures 38.19–38.21). Metaanalysis failed to demonstrate a significant reduction in severity and mortality for ERCP in patients with acute biliary pancreatitis undergoing urgent ERCP. Treatment for bile duct stones with the use of ERCP/sphincterotomy alone is not recommended in cases of gallstone‐induced pancreatitis with gallbladder stones. Cholecystectomy for gallstone‐induced acute pancreatitis should be performed using a laparoscopic procedure after resolution of acute pancreatitis.

Plain films of the abdomen and lung should be considered if an intestinal perforation is suspected and if free air is found, CT should be performed. If the diagnosis of acute pancreatitis is established by abdominal pain and increased levels of pancreatic enzyme activities, a CECT scan is not usually required for diagnosis in the emergency room or on admission to the hospital for three reasons:

• while local complications may be identified during the early phase, it is generally not necessary to document local complications by imaging during the first week if the course is uncomplicated
  
• CECT 5–7 days after admission is more reliable in establishing the presence and extent of pancreatic necrosis
  
• in any case, no treatment for peripancreatic fluid collections or pancreatic necrosis is generally warranted sooner.

Computed tomography currently plays an important role in imaging of patients with acute pancreatitis, the identification of complications (Figure 38.22), and assessing the response to treatment. The revision of the Atlanta classification in 2012 presented a standardized template for reporting CT images (Tables 38.5 and 38.6, Box 38.2).

Fluid collections that develop in the early phase of pancreatitis are termed acute peripancreatic fluid collections (APFC). Most APFC are sterile and resolve spontaneously, but can persist beyond 4 weeks. The latter APFC can uncommonly develop into pancreatic pseudocysts. However, leakage of pancreatic ducts commonly results in pseudocyst formation. Pancreatic pseudocysts are collections surrounded by a well‐defined wall without solid material or detritus (Figure 38.23). In contrast, a collection of variable amounts of fluid and necrotic tissue is called an acute necrotic collection (ANC). ANC occurs in necrotizing pancreatitis and is distinct from APFC. Early on, it may be difficult to differentiate APFC from ANC because both types of collections appear as areas with fluid density. After the first week, distinction between these two types of collections is usually possible. When a contrast‐enhancing wall of reactive tissue develops around necrotic pancreatic areas, the collection is termed walled‐off necrosis; this usually occurs 4 weeks after onset of necrotizing pancreatitis. The presence of gas within the collection seen on CECT is suspicious for superinfection (Figure 38.24). Fine needle aspiration is useful to ascertain diagnosis and to obtain a specimen for culture.