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Acute Pancreatitis Author: Timothy B Gardner, MD; Chief Editor: BS Anand, MD more...

Updated: Dec 8, 2014

Practice EssentialsRecognizing patients with severe acute pancreatitis as soon as possible is critical for achieving optimal outcomes.Management depends largely on severity. Medical treatment of mild acute pancreatitis is relatively straightforward.Treatment of severe acute pancreatitis involves intensive care. Surgical intervention (open or minimally invasive) isindicated in selected cases.

Essential update: Trial finds no superiority of early nasoenteric tube feeding compared withoral diet in acute pancreatitis

Early nasoenteric tube feeding was not superior to an oral diet initiated 72 hours after presentation in a randomized,multicenter study of 208 patients with acute pancreatitis. Tube feeding was provided if the oral diet was not tolerated.[1]

During 6 months of follow­up, major infection or death occurred in 30 of 101 patients (30%) in the early nasoenterictube feeding group and in 28 of 104 patients (27%) in the oral diet group (risk ratio, 1.07; 95% confidence interval,0.79 to 1.44; P = 0.76). Of the 104 patients in the oral diet group, 72 (69%) did not require tube feeding.[1]

Signs and symptoms

Symptoms of acute pancreatitis include the following:

Abdominal pain (cardinal symptom): Characteristically dull, boring, and steady; usually sudden in onset andgradually becoming more severe until reaching a constant ache; most often located in the upper abdomenand may radiate directly through to the backNausea and vomiting, sometimes with anorexiaDiarrhea

Patients may have a history of the following:

Recent operative or other invasive proceduresFamily history of hypertriglyceridemiaPrevious biliary colic and binge alcohol consumption (major causes of acute pancreatitis)

The following physical findings may be noted, varying with the severity of the disease:

Fever (76%) and tachycardia (65%); hypotensionAbdominal tenderness, muscular guarding (68%), and distention (65%); diminished or absent bowel soundsJaundice (28%)Dyspnea (10%); tachypnea; basilar rales, especially in the left lungIn severe cases, hemodynamic instability (10%) and hematemesis or melena (5%); pale, diaphoretic, andlistless appearanceOccasionally, extremity muscular spasm secondary to hypocalcemia

The following uncommon physical findings are associated with severe necrotizing pancreatitis:

Cullen sign (bluish discoloration around the umbilicus resulting from hemoperitoneum)Grey­Turner sign (reddish­brown discoloration along the flanks resulting from retroperitoneal blood dissectingalong tissue planes); more commonly, patients may have a ruddy erythema in the flanks secondary toextravasated pancreatic exudateErythematous skin nodules, usually no larger than 1 cm and typically located on extensor skin surfaces;polyarthritis

See Clinical Presentation for more detail.

Diagnosis

Once a working diagnosis of acute pancreatitis is reached, laboratory tests are obtained to support the clinicalimpression, such as the following:

Serum amylase and lipaseLiver­associated enzymesBlood urea nitrogen (BUN), creatinine, and electrolytesBlood glucoseSerum cholesterol and triglycerideComplete blood count (CBC) and hematocrit; NLRC­reactive protein (CRP)Arterial blood gas valuesSerum lactic dehydrogenase (LDH) and bicarbonateImmunoglobulin G4 (IgG4)

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Diagnostic imaging is unnecessary in most cases but may be obtained when the diagnosis is in doubt, whenpancreatitis is severe, or when a given study might provide specific information required. Modalities employedinclude the following:

Abdominal radiography (limited role): Kidneys­ureters­bladder (KUB) radiography with the patient upright isprimarily performed to detect free air in the abdomenAbdominal ultrasonography (most useful initial test in determining the etiology, and is the technique of choicefor detecting gallstones)Endoscopic ultrasonography (EUS) (used mainly for detection of microlithiasis and periampullary lesions noteasily revealed by other methods)Abdominal computed tomography (CT) scanning (generally not indicated for patients with mild pancreatitis butalways indicated for those with severe acute pancreatitis)Endoscopic retrograde cholangiopancreatography (ERCP; to be used with extreme caution in this diseaseand never as a first­line diagnostic tool [2] )Magnetic resonance cholangiopancreatography (MRCP; not as sensitive as ERCP but safer and noninvasive)

Other diagnostic modalities include the following:

CT­guided or EUS­guided aspiration and drainageGenetic testing

Acute pancreatitis is broadly classified as either mild or severe. According to the Atlanta classification, severe acutepancreatitis is signaled by the following[3] :

Evidence of organ failure (eg, systolic blood pressure below 90 mm Hg, arterial partial pressure of oxygen [Pa O 2] 60 mm Hg or lower, serum creatinine level 2 mg/dL or higher, GI bleeding amounting to 500 mL ormore in 24 hours)Local complications (eg, necrosis, abscess, pseudocyst)Ranson score of 3 or higher or APACHE score of 8 or higher

See Workup for more detail.

Management

Medical management of mild acute pancreatitis is relatively straightforward; however, patients with severe acutepancreatitis require intensive care.

Initial supportive care includes the following:

Fluid resuscitation [4]Nutritional support

Antibiotic therapy is employed as follows:

Antibiotics (usually of the imipenem class) should be used in any case of pancreatitis complicated by infectedpancreatic necrosis but should not be given routinely for fever, especially earlyAntibiotic prophylaxis in severe pancreatitis is controversial; routine use of antibiotics as prophylaxis againstinfection in severe acute pancreatitis is not currently recommended

Surgical intervention (open or minimally invasive) is indicated when an anatomic complication amenable to amechanical solution is present. Procedures appropriate for specific conditions involving pancreatitis include thefollowing:

Gallstone pancreatitis: CholecystectomyPancreatic duct disruption: Image­guided percutaneous placement of a drainage tube into the fluid collection[5] ; stent or tube placement via ERCP; in refractory cases, distal pancreatectomy or a Whipple procedurePseudocysts: None necessary in most cases; for large or symptomatic pseudocysts, percutaneous aspiration,endoscopic transpapillary or transmural techniques, or surgical managementInfected pancreatic necrosis: Image­guided aspiration; necrosectomyPancreatic abscess: Percutaneous catheter drainage and antibiotics; if no response, surgical debridementand drainage

See Treatment and Medication for more detail.

BackgroundThis article focuses on the recognition and management of acute pancreatitis. Pancreatitis is an inflammatoryprocess in which pancreatic enzymes autodigest the gland. The gland sometimes heals without any impairment offunction or any morphologic changes; this process is known as acute pancreatitis. Pancreatitis can also recurintermittently, contributing to the functional and morphologic loss of the gland; recurrent attacks are referred to aschronic pancreatitis.

Both forms of pancreatitis may present in the emergency department (ED) with acute clinical findings. Recognizingpatients with severe acute pancreatitis as soon as possible is critical for achieving optimal outcomes (seePresentation).

Once a working diagnosis of acute pancreatitis is reached, laboratory tests are obtained to support the clinicalimpression, to help define the etiology, and to look for complications. Diagnostic imaging is unnecessary in mostcases but may be obtained when the diagnosis is in doubt, when severe pancreatitis is present, or when a givenimaging study might provide specific information needed to answer a clinical question. Image­guided aspiration maybe useful. Genetic testing may be considered (see Workup).

Management depends largely on severity. Medical treatment of mild acute pancreatitis is relatively straightforward.Treatment of severe acute pancreatitis involves intensive care; the goals of medical management are to provide

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aggressive supportive care, to decrease inflammation, to limit infection or superinfection, and to identify and treatcomplications as appropriate. Surgical intervention (open or minimally invasive) is indicated in selected cases (seeTreatment).

The American College of Gastroenterology recently issued guidelines for the management of acute pancreatitis.[6]These include the following:

Because acute pancreatitis can usually be diagnosed based on clinical symptoms and laboratory testing,contrast­enhanced computed tomography (CT) scanning and/or magnetic resonance imaging (MRI) of thepancreas should be performed only in the absence of clinical improvement or if the diagnosis is unclearAssessment of the patient’s hemodynamic status should occur immediately upon presentation, withresuscitative measures initiated as necessaryPatients with systemic inflammatory response syndrome (SIRS) and/or organ failure should, if possible, beadmitted to an intensive care unit (ICU) or an intermediary care settingAll patients should receive aggressive hydration, unless this is precluded by cardiovascular and/or renalcomorbidities; aggressive intravenous (IV) hydration is most effective within the first 12­24 hours, withpossibly little benefit derived from its administration after this pointWithin 24 hours of admission, patients with concurrent acute cholangitis should undergo endoscopicretrograde cholangiopancreatography (ERCP); in high­risk patients, the risk of severe post­ERCP pancreatitisshould be reduced through the use of postprocedure rectal nonsteroidal anti­inflammatory drug (NSAID)suppositories and/or pancreatic duct stentsThe guidelines recommend against routinely using prophylactic antibiotics in cases of severe acutepancreatitis and/or sterile necrosis; however, intervention in patients with infected necrosis may be delayedthrough the use of antibiotics that do not penetrate the necrotic tissueIn mild cases of acute pancreatitis with no nausea and vomiting, oral feeding can be initiated immediately;enteral nutrition should be used in severe cases to prevent infectious complications, and parenteral nutritionshould be avoidedRegardless of lesion size, location, and/or extension, intervention is not necessary for asymptomaticpancreatic and/or extrapancreatic necrosis and/or pseudocystsSurgical, radiologic, and/or endoscopic drainage in stable patients with infected necrosis should be postponed(for 4 weeks if possible) to permit a wall to develop around the necrosis

Pathophysiology

Normal pancreatic function

The pancreas is a gland located in the upper posterior abdomen. It is responsible for insulin production (endocrinepancreas) and the manufacture and secretion of digestive enzymes (exocrine pancreas) leading to carbohydrate, fat,and protein metabolism. Approximately 80% of the gross weight of the pancreas supports exocrine function, and theremaining 20% is involved with endocrine function. The focus of this article is on the exocrine function of thepancreas.

The pancreas accounts for only 0.1% of total body weight but has 13 times the protein­producing capacity of the liverand the reticuloendothelial system combined, which together make up 4% of total body weight. Digestive enzymesare produced within the pancreatic acinar cells, packaged into storage vesicles called zymogens, and then releasedvia the pancreatic ductal cells into the pancreatic duct, where they are secreted into the small intestine to begin themetabolic process.

In normal pancreatic function, up to 15 different types of digestive enzymes are manufactured in the roughendoplasmic reticulum, targeted in the Golgi apparatus and packaged into zymogens as proenzymes. When a mealis ingested, the vagal nerves, vasoactive intestinal polypeptide (VIP), gastrin­releasing peptide (GRP), secretin,cholecystokinin (CCK), and encephalins stimulate release of these proenzymes into the pancreatic duct.

The proenzymes travel to the brush border of the duodenum, where trypsinogen, the proenzyme for trypsin, isactivated via hydrolysis of an N­terminal hexapeptide fragment by the brush border enzyme enterokinase. Trypsinthen facilitates the conversion of the other proenzymes to their active forms.

A feedback mechanism exists to limit pancreatic enzyme activation after appropriate metabolism has occurred. It ishypothesized that elevated levels of trypsin, having become unbound from digesting food, lead to decreased CCKand secretin levels, thus limiting further pancreatic secretion.

Because premature activation of pancreatic enzymes within the pancreas leads to organ injury and pancreatitis,several mechanisms exist to limit this occurrence. First, proteins are translated into the inactive proenzymes. Later,posttranslational modification of the Golgi cells allows their segregation into the unique subcellular zymogencompartments. The proenzymes are packaged in a paracrystalline arrangement with protease inhibitors.

Zymogen granules have an acidic pH and a low calcium concentration, which are factors that guard againstpremature activation until after secretion has occurred and extracellular factors have triggered the activationcascade. Under various conditions, disruption of these protective mechanisms may occur, resulting in intracellularenzyme activation and pancreatic autodigestion leading to acute pancreatitis.

Pathogenesis of acute pancreatitis

Acute pancreatitis may occur when factors involved in maintaining cellular homeostasis are out of balance. Theinitiating event may be anything that injures the acinar cell and impairs the secretion of zymogen granules; examplesinclude alcohol use, gallstones, and certain drugs.

At present, it is unclear exactly what pathophysiologic event triggers the onset of acute pancreatitis. It is believed,however, that both extracellular factors (eg, neural and vascular response) and intracellular factors (eg, intracellulardigestive enzyme activation, increased calcium signaling, and heat shock protein activation) play a role. In addition,acute pancreatitis can develop when ductal cell injury leads to delayed or absent enzymatic secretion, as seen inpatients with the CFTR gene mutation.

Once a cellular injury pattern has been initiated, cellular membrane trafficking becomes chaotic, with the following

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deleterious effects:

Lysosomal and zymogen granule compartments fuse, enabling activation of trypsinogen to trypsin

Intracellular trypsin triggers the entire zymogen activation cascade

Secretory vesicles are extruded across the basolateral membrane into the interstitium, where molecular

fragments act as chemoattractants for inflammatory cells

Activated neutrophils then exacerbate the problem by releasing superoxide (the respiratory burst) or proteolytic

enzymes (cathepsins B, D, and G; collagenase; and elastase). Finally, macrophages release cytokines that further

mediate local (and, in severe cases, systemic) inflammatory responses. The early mediators defined to date are

tumor necrosis factor­alpha (TNF­α), interleukin (IL)­6, and IL­8.

These mediators of inflammation cause an increased pancreatic vascular permeability, leading to hemorrhage,

edema, and eventually pancreatic necrosis. As the mediators are excreted into the circulation, systemic

complications can arise, such as bacteremia due to gut flora translocation, acute respiratory distress syndrome

(ARDS), pleural effusions, gastrointestinal (GI) hemorrhage, and renal failure.

The systemic inflammatory response syndrome (SIRS) can also develop, leading to the development of systemic

shock. Eventually, the mediators of inflammation can become so overwhelming to the body that hemodynamic

instability and death ensue.

In acute pancreatitis, parenchymal edema and peripancreatic fat necrosis occur first; this is known as acute

edematous pancreatitis. When necrosis involves the parenchyma, accompanied by hemorrhage and dysfunction of

the gland, the inflammation evolves into hemorrhagic or necrotizing pancreatitis. Pseudocysts and pancreatic

abscesses can result from necrotizing pancreatitis because enzymes can be walled off by granulation tissue

(pseudocyst formation) or via bacterial seeding of pancreatic or peripancreatic tissue (pancreatic abscess formation).

Li et al compared 2 set of patients with severe acute pancreatitis—one with acute renal failure and the other without

it—and determined that a history of renal disease, hypoxemia, and abdominal compartment syndrome are significant

risk factors for acute renal failure in patients with severe acute pancreatitis.[7] In addition, patients with acute renal

failure were found to have a significantly greater average length of stay in the hospital and in the intensive care unit

(ICU), as well as higher rates of pancreatic infection and mortality.

EtiologyLong­standing alcohol consumption and biliary stone disease cause most cases of acute pancreatitis, but numerous

other etiologies are known. In 10­30% of cases, the cause is unknown, though studies have suggested that as many

as 70% of cases of idiopathic pancreatitis are secondary to biliary microlithiasis.

Biliary tract disease

One of the most common causes of acute pancreatitis in most developed countries (accounting for approximately

40% of cases) is gallstones passing into the bile duct and temporarily lodging at the sphincter of Oddi. The risk of a

stone causing pancreatitis is inversely proportional to its size.

It is thought that acinar cell injury occurs secondary to increasing pancreatic duct pressures caused by obstructive

biliary stones at the ampulla of Vater, although this has not been definitively proven in humans. Occult microlithiasis

is probably responsible for most cases of idiopathic acute pancreatitis.

Alcohol

Alcohol use is a major cause of acute pancreatitis (accounting for at least 35% of cases[8] ). At the cellular level,

ethanol leads to intracellular accumulation of digestive enzymes and their premature activation and release. At the

ductal level, it increases the permeability of ductules, allowing enzymes to reach the parenchyma and cause

pancreatic damage. Ethanol increases the protein content of pancreatic juice and decreases bicarbonate levels and

trypsin inhibitor concentrations. This leads to the formation of protein plugs that block pancreatic outflow.

Most commonly, the disease develops in patients whose alcohol ingestion is habitual over 5­15 years. Alcoholics are

usually admitted with an acute exacerbation of chronic pancreatitis. Occasionally, however, pancreatitis can develop

in a patient with a weekend binging habit, and several case reports have described a sole large alcohol load

precipitating a first attack. Nevertheless, the alcoholic who imbibes routinely remains the rule rather than the

exception.

Currently, there is no universally accepted explanation for why certain alcoholics are more predisposed to developing

acute pancreatitis than other alcoholics who ingest similar quantities.

Endoscopic retrograde cholangiopancreatography

Pancreatitis occurring after endoscopic retrograde cholangiopancreatography (ERCP) is probably the third most

common type (accounting for approximately 4% of cases). Whereas retrospective surveys indicate that the risk is

only 1%, prospective studies have shown the risk to be at least 5%.

The risk of post­ERCP acute pancreatitis is increased if the endoscopist is inexperienced, if the patient is thought to

have sphincter of Oddi dysfunction, or if manometry is performed on the sphincter of Oddi. No medical measures,

with the exception of aggressive preintervention intravenous (IV) hydration, have been durably shown to prevent

post­ERCP pancreatitis in randomized studies.

Trauma

Abdominal trauma (approximately 1.5%) causes an elevation of amylase and lipase levels in 17% of cases and

clinical pancreatitis in 5% of cases. Pancreatic injury occurs more often in penetrating injuries (eg, from knives,

bullets) than in blunt abdominal trauma (eg, from steering wheels, horses, bicycles). Blunt injury to the abdomen or

back may crush the gland across the spine, leading to a ductal injury.

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Drugs

Considering the small number of patients who develop pancreatitis compared to the relatively large number whoreceive potentially toxic drugs, drug­induced pancreatitis is a relatively rare occurrence (accounting for approximately2% of cases) that is probably related to an unknown predisposition. Fortunately, drug­induced pancreatitis is usuallymild.

Drugs definitely associated with acute pancreatitis include the following:

AzathioprineSulfonamidesSulindacTetracyclineValproic acid,DidanosineMethyldopaEstrogensFurosemide6­MercaptopurinePentamidine5­aminosalicylic acid compoundsCorticosteroidsOctreotide

Drugs probably associated with acute pancreatitis include the following:

Chlorothiazide and hydrochlorothiazideMethandrostenolone (methandienone)MetronidazoleNitrofurantoinPhenforminPiroxicamProcainamideColaspaseChlorthalidoneCombination cancer chemotherapy drugs (especially asparaginase)CimetidineCisplatinCytosine arabinosideDiphenoxylateEthacrynic acid

In addition, there are many drugs that have been reported to cause acute pancreatitis in isolated or sporadic cases.

Less common causes

The following causes each account for less than 1% of cases of pancreatitis.

Infection

Several infectious diseases may cause pancreatitis, especially in children. These cases of acute pancreatitis tend tobe milder than cases of acute biliary or alcohol­induced pancreatitis.

Viral causes include mumps virus, coxsackievirus, cytomegalovirus (CMV), hepatitis virus, Epstein­Barr virus (EBV),echovirus, varicella­zoster virus (VZV), measles virus, and rubella virus. Bacterial causes include Mycoplasmapneumoniae, Salmonella, Campylobacter, and Mycobacterium tuberculosis. Worldwide, Ascaris is a recognizedcause of pancreatitis resulting from the migration of worms in and out of the duodenal papillae.

Pancreatitis has been associated with AIDS; however, this may be the result of opportunistic infections, neoplasms,lipodystrophy, or drug therapies.

Hereditary pancreatitis

Hereditary pancreatitis is an autosomal dominant gain­of­function disorder related to mutations of the cationictrypsinogen gene (PRSS1), which has an 80% penetrance. Mutations in this gene cause premature activation oftrypsinogen to trypsin.

In addition, the CFTR mutation plays a role in predisposing patients to acute pancreatitis by causing abnormalities ofductal secretion. At present, however, the phenotypic variability of patients with the CFTR mutation is not wellunderstood. Certainly, patients homozygous for the CFTR mutation are at risk for pancreatic disease, but it is not yetclear which of the more than 800 mutations carries the most significant risk. In addition, the role of CFTRheterozygotes in pancreatic disease is unknown.

Mutations in the SPINK1 protein, which blocks the active binding site of trypsin, rendering it inactive, also probablyplay a role in causing a predisposition to acute pancreatitis.

This probably explains the predisposition, rather than the cause, of acute pancreatitis in these patients. If enoughmutant enzymes become activated intracellularly, they can overwhelm the first line of defense (ie, pancreaticsecretory trypsin inhibitor) and resist backup defenses (ie, proteolytic degradation by mesotrypsin, enzyme Y, andtrypsin itself). Activated mutant cationic trypsin can then trigger the entire zymogen activation cascade.

Hypercalcemia

Hypercalcemia from any cause can lead to acute pancreatitis. Causes include hyperparathyroidism, excessive dosesof vitamin D, familial hypocalciuric hypercalcemia, and total parenteral nutrition (TPN). Routine use of automatedserum chemistries has allowed earlier detection and reduced the frequency of hypercalcemia manifesting as

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pancreatitis.

Developmental abnormalities of pancreas

The pancreas develops from 2 buds stemming from the alimentary tract of the developing embryo. There are 2developmental abnormalities commonly associated with pancreatitis: pancreas divisum and annular pancreas.

Pancreas divisum is a failure of the dorsal and ventral pancreatic ducts to fuse during embryogenesis. Probably avariant of normal anatomy, it occurs in approximately 5% of the population (see the images below); in most cases, itmay actually protect against gallstone pancreatitis. It appears that the presence of stenotic minor papillae and anatretic duct of Santorini are additional risk factors that together contribute to the development of acute pancreatitisthrough an obstructive mechanism (although this is controversial).

Pancreas divisum associated with minor papilla stenosis causing recurrent pancreatitis. Because pancreas divisum is relativelycommon in general population, it is best regarded as variant of normal anatomy and not necessarily as cause of pancreatitis. Inthis case, note bulbous contour of duct adjacent to cannula. This appearance has been termed Santorinicele. Dorsal duct outflowobstruction is a probable cause of pancreatitis when Santorinicele is present and associated with a minor papilla thataccommodates only guide wire.

Recurrent pancreatitis associated with pancreas divisum in an elderly man. Pancreatogram of the dorsal duct shows distalstenosis with upstream chronic pancreatitis. After the stenosis was dilated and stented, pain resolved and the patient improvedclinically during 1 year of quarterly stent exchanges. Follow­up CT scans showed resolution of the inflammatory mass. Althoughductal biopsies and cytology were repeatedly negative, pain and pancreatitis returned when stents were removed. Patientdeveloped duodenal outflow obstruction and was sent to surgery; Whipple procedure revealed periampullary adenocarcinoma (ofminor papilla).

Annular pancreas is an uncommon congenital anomaly in which a band of pancreatic tissue surrounds the secondpart of the duodenum. Usually, it does not cause symptoms until later in life. This condition is a rare cause of acutepancreatitis, probably through an obstructive mechanism.

Sphincter of Oddi dysfunction can lead to acute pancreatitis by causing increased pancreatic ductal pressures.However, the role of pancreatitis induced by such dysfunction in patients without elevated sphincter pressures onmanometry remains controversial.

Hypertriglyceridemia

Clinically significant pancreatitis usually does not occur until a person’s serum triglyceride level reaches 1000 mg/dL.It is associated with type I and type V hyperlipidemia. Although this view is somewhat controversial, most authoritiesbelieve that the association is caused by the underlying derangement in lipid metabolism rather than by pancreatitiscausing hyperlipidemia. This type of pancreatitis tends to be more severe than alcohol­ or gallstone­induced disease.

Tumors

Obstruction of the pancreatic ductal system by a pancreatic ductal carcinoma, ampullary carcinoma, islet cell tumor,solid pseudotumor of the pancreas, sarcoma, lymphoma, cholangiocarcinoma, or metastatic tumor can cause acutepancreatitis. The chance of pancreatitis occurring when a tumor is present is approximately 14%. Pancreatic cysticneoplasm, such as intraductal papillary­mucinous neoplasm (IPMN), mucinous cystadenoma, or serouscystadenoma, can also cause pancreatitis.

Toxins

Exposure to organophosphate insecticide can cause acute pancreatitis. Scorpion and snake bites may also becausative; in Trinidad, the sting of the scorpion Tityus trinitatis is the most common cause of acute pancreatitis.Hyperstimulation of pancreas exocrine secretion appears to be the mechanism of action in both instances.

Surgical procedures

Acute pancreatitis may occur in the postoperative period of various surgical procedures (eg, abdominal orcardiopulmonary bypass surgery, which may damage the gland by causing ischemia). Postoperative acutepancreatitis is often a difficult diagnosis to confirm, and it has a higher complication rate than pancreatitis associatedwith other etiologies. The mechanism is unclear.

Vascular abnormalities

Vascular factors, such as ischemia or vasculitis, can play a role in causing acute pancreatitis. Vasculitis canpredispose patients to pancreatic ischemia, especially in those with polyarteritis nodosa and systemic lupuserythematosus.

Autoimmune pancreatitis

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Autoimmune pancreatitis, a relatively newly described entity, is an extremely rare cause of acute pancreatitis

(prevalence, 0.82 per 100,000 individuals). When it does cause acute pancreatitis, it is usually in young people

(approximately 40 years) who also suffer from inflammatory bowel disease. The pathogenesis is unclear.

Epidemiology

United States statistics

Acute pancreatitis has an incidence of approximately 40 cases per year per 100,000 adults.[9] In 2007, nearly

220,000 patients with acute pancreatitis are expected to be admitted to non–federally funded hospitals. In 1998,

183,000 patients with acute pancreatitis were admitted. This trend in rising incidence has been recognized over the

past several decades.[10]

International statistics

Worldwide, the incidence of acute pancreatitis ranges between 5 and 80 per 100,000 population, with the highest

incidence recorded in the United States and Finland.[11]

In Luneburg, Germany, the incidence is 17.5 cases per

100,000 people. In Finland, the incidence is 73.4 cases per 100,000 people. Similar incidence rates have been

reported in Australia. The incidence of disease outside North America, Europe, and Australia is less well known.

In Europe and other developed nations, such as Hong Kong, more patients tend to have gallstone pancreatitis,

whereas in the United States, alcoholic pancreatitis is most common.

Age­related demographics

The median age at onset depends on the etiology.[12]

The following are median ages of onset for various etiologies:

Alcohol­related ­ 39 years

Biliary tract–related ­ 69 years

Trauma­related ­ 66 years

Drug­induced etiology ­ 42 years

ERCP­related ­ 58 years

AIDS­related ­ 31 years

Vasculitis­related ­ 36 years

Hospitalization rates increase with age. For people aged 35­75 years, the rate doubles for males and quadruples for

females.

Sex­related demographics

Generally, acute pancreatitis affects males more often than females. In males, the etiology is more often related to

alcohol; in females, it is more often related to biliary tract disease. Idiopathic pancreatitis has no clear predilection for

either sex.

Race­related demographics

The hospitalization rates of patients with acute pancreatitis per 100,000 population are 3 times higher for blacks than

whites. These racial differences are more pronounced for males than females. The risk for African Americans aged

35­64 years is 10 times higher than for any other group. African Americans are at a higher risk than whites in that

same age group.

The annual incidence of acute pancreatitis in Native Americans is 4 per 100,000 population; in whites, 5.7 per

100,000 population; and in blacks, 20.7 per 100,000 population.[13]

PrognosisThe overall mortality in patients with acute pancreatitis is 10­15%. Patients with biliary pancreatitis tend to have a

higher mortality than patients with alcoholic pancreatitis. This rate has been falling over the last 2 decades as

improvements in supportive care have been initiated. In patients with severe disease (organ failure), who account for

about 20% of presentations, mortality is approximately 30%.[14]

This figure has not decreased in the past 10 years. In

patients with pancreatic necrosis without organ failure, the mortality approaches zero.

In the first week of illness, most deaths result from multiorgan system failure. In subsequent weeks, infection plays a

more significant role, but organ failure still constitutes a major cause of mortality. Acute respiratory distress

syndrome (ARDS), acute renal failure, cardiac depression, hemorrhage, and hypotensive shock all may be systemic

manifestations of acute pancreatitis in its most severe form.

Identifying patients in greatest need of aggressive medical treatment by differentiating their disease severity as mild

or severe is recommended. In mild disease, the pancreas exhibits interstitial edema, an inflammatory infiltrate

without hemorrhage or necrosis, and, usually, minimal or no organ dysfunction. In severe disease, the inflammatory

infiltrate is severe, associated with necrosis of the parenchyma, often accompanied by evidence of severe gland

dysfunction, and it may be associated with multiorgan system failure.

Different strategies have been used to assess the severity of acute pancreatitis and predict outcome (see Workup

and Staging). Several clinical scoring systems (eg, Ranson criteria, Glasgow, Imrie) are available. The APACHE II

scoring system, though cumbersome, appears to be the best validated (see the APACHE II Scoring System

calculator). Biological markers have also been used for this purpose. Genetic markers are being studied and have

not yet come into clinical use.

Peritoneal lavage has a high specificity (93%); however, it has a low sensitivity (54%). Dynamic CT scanning of the

abdomen is widely available and useful in predicting the outcome of acute pancreatitis. When the Balthazar criteria

(see Workup and Computed Tomography) are used, sensitivity is 87% and specificity is 88%.

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Suppiah et al examined the prognostic value of the neutrophil­lymphocyte ratio (NLR) in 146 consecutive patientswith acute pancreatitis.[15] They found that elevation of the NLR during the first 48 hours of hospital admission wassignificantly associated with severe acute pancreatitis and was an independent negative prognostic indicator. TheNLR is calculated from the white cell differential and provides an indication of inflammation.

Patient EducationEducate patients about the disease, and advise them to avoid alcohol in binge amounts and to discontinue any riskfactor, such as fatty meals and abdominal trauma.

For patient education resources, see the Cholesterol Center, as well as Pancreatitis and Gallstones.

Contributor Information and DisclosuresAuthorTimothy B Gardner, MD Assistant Professor, Department of Medicine, Dartmouth Medical School; Director ofPancreatic Disorders, Section of Gastroenterology, Dartmouth­Hitchcock Medical Center

Timothy B Gardner, MD is a member of the following medical societies: American College of Gastroenterology,American College of Physicians­American Society of Internal Medicine, American GastroenterologicalAssociation, American Medical Association, American Pancreatic Association, and American Society forGastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Coauthor(s)Brian S Berk, MD Assistant Professor, Department of Medicine, Dartmouth Medical School; Director of EndStage Liver Disease, Section of Gastroenterology, Dartmouth Hitchcock Medical Center

Brian S Berk, MD is a member of the following medical societies: American Association for the Study of LiverDiseases, American College of Gastroenterology, and American Gastroenterological Association

Disclosure: Nothing to disclose.

Chief EditorBS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College ofMedicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of LiverDiseases, American College of Gastroenterology, American Gastroenterological Association, and AmericanSociety for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Additional ContributorsTushar Patel, MB, ChB Professor of Medicine, Ohio State University Medical Center

Tushar Patel, MB, ChB is a member of the following medical societies: American Association for the Study ofLiver Diseases and American Gastroenterological Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center Collegeof Pharmacy; Editor­in­Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Noel Williams, MD Professor Emeritus, Department of Medicine, Dalhousie University, Halifax, Nova Scotia,Canada; Professor, Department of Internal Medicine, Division of Gastroenterology, University of Alberta,Edmonton, Alberta, Canada

Noel Williams, MD is a member of the following medical societies: Royal College of Physicians and Surgeons ofCanada

Disclosure: Nothing to disclose.

Paul Yakshe, MD Assistant Professor of Medicine, University of Minnesota, Medical Director of Pancreas andBiliary Clinic, Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, FairviewUniversity Medical Center

Paul Yakshe, MD is a member of the following medical societies: American College of Gastroenterology,American Pancreatic Association, and American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

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