Acute pancreatitis is a potentially lethal disease that is increasing in incidence. Incidence varies from 4.5 to 79.8 per 100,000 per year in different countries, with incidence in the UK reported at approximately 56 per 100,000 per year.[7] The variation in incidence between different countries is due to different diagnostic criteria, geographical factors, and changes over time.[8] A 10-fold increase in its incidence from 1960 to 1980, with a mortality rate from 1% to 9%, was noted.[9] The overall mortality rate in the UK is reported as around 5%, rising to 25% for patients with severe disease.[7] In the UK, around 50% of cases are caused by gallstones, 25% by alcohol, and 25% by other factors.[7] Gallstone pancreatitis is more common in white women >60 years of age, especially among patients with microlithiasis. Alcoholic pancreatitis is seen more frequently in men.[10]

Risk factors

Women between 50 and 70 years of age are more likely to have gallbladder disease and may present with pancreatitis at later age than men with alcoholic pancreatitis (40 to 55 years of age).

Mostly associated with high alcohol intake.

Gallstone pancreatitis accounts for 45% to 50% of acute pancreatitis in the US.[14] It is seen more frequently in older women and those with history of gallstone disease. Impaction of a stone within the common bile duct causes reflux of biliohepatic secretions and intra-pancreatic enzymatic activation. Stones may cause inflammation and oedema of the ducts, causing some degree of flow restriction and backflow of activated enzymes into the pancreas.[14]

Ethanol causes 40% to 45% of all cases of acute pancreatitis and is the most common cause of acute pancreatitis in men. A dose-related destruction to the pancreatic parenchyma has been described. This form of pancreatitis is more commonly seen in men than in women and is usually seen after periods of binge drinking. There is no threshold for the development of acute pancreatitis. The average amount of alcohol intake in patients with acute pancreatitis is 150 to 175 g per day.[9][14]

It has been suggested that the pancreatic lipase can produce toxic fatty acids that are secreted into the pancreatic micro-circulation, leading to endothelial injury and ischaemic insult to the acinar cell.[11] Many patients with acute pancreatitis demonstrate an acute increase in circulating triglycerides in the range of 5 or 6 mmol/L (a few hundred mg/dL). However, patients with true hypertriglyceridaemia-induced acute pancreatitis manifest a substantial increase in circulating triglycerides, commonly over 22 or 23 mmol/L (2000 mg/dL).[15]

Azathioprine: mechanisms suggested for drug-induced pancreatitis include pancreatic duct constriction; immunosuppression; cytotoxic, osmotic, pressure, or metabolic effects; arteriolar thrombosis; direct cellular toxicity; and hepatic involvement.[12]

Thiazide diuretics: thought to cause pancreatitis by affecting the acinar cells.[12]

Furosemide: causes pancreatitis by an undefined immunological pathway.[12][18]

Other drugs known to cause pancreatitis include: sulfonamides, tetracyclines, oestrogens, didanosine, sulindac, mercaptopurine, valproic acid, dipeptidyl peptidase-4 inhibitors, and L-asparaginase.[12][19]

The use of contrast during ERCP has been linked to pancreatic inflammation. The incidence of ERCP-induced pancreatitis is 2% to 3%, and some studies have shown some risk reduction with the use of non-steroidal anti-inflammatory agents,[20][21][22][23] pancreatic stents, and octreotide infusion. The risk of ERCP-induced pancreatitis is slightly increased in young females, in patients with impacted stones or oedema of the ampulla or bile duct, and during technically demanding procedures.[24][25][26]

Traumatic pancreatitis can be caused by therapeutic or diagnostic procedures or during external trauma. Blunt trauma is the most common cause of pancreatic injury and can be associated with parenchymal inflammation and hyperamylasaemia. Given that the pancreas is a retroperitoneal organ, trauma is not a common aetiological factor but its incidence may be under-reported, because patients may not have a clear clinical manifestation.[11]

This is quite rare and the exact mechanisms are not well understood.[27][28]

This is quite rare and the exact mechanisms are not well understood.[27][28]

Causal mechanisms are still not completely understood. Animal studies have shown that calcium has a direct toxic effect on the pancreatic acinar cell. Other proposed pathophysiological mechanisms include accumulation of zymogen granules in the cytoplasm, cytoplasmic vacuolisation, focal acinar depolarisation, acinar necrosis, increased amylase secretion,[16][17] and formation of calcified stones intraductally.[11]

Thought to cause pancreatitis by infecting the acinar cells.[12][18]

Thought to cause pancreatitis by infecting the acinar cells.[12][18]

Thought to cause pancreatitis by infecting the acinar cells.[12][18]

During organogenesis, the pancreas derives from the foregut after the fusion of the larger dorsal bud and the smaller ventral bud. The smaller accessory duct of Santorini drains the pancreatic structures that derive from the dorsal bud (upper half of the head, neck, body, and tail), whereas the larger duct of Wirsung drains the ventral bud (lower part of the head and uncinate process). Failure of the rotation of the ventral bud prevents fusion of both ducts, making the drainage of the dorsal bud derivates insufficient, which can lead to acute pancreatitis.[14] The role of endoscopic sphincterotomy of the minor papilla and stenting of the dorsal duct may decrease the recurrence of pancreatitis but its role for pain control has not been demonstrated.[29]

The most common primary malignancy of the pancreas is the adenocarcinoma. Cancer has been implicated as a potential risk factor for the development of pancreatitis if it causes duct obstruction. It has been reported that 1% to 2% of acute pancreatitis may be attributed to peri-ampullary tumours.[11]

Oddi's dysfunction can be primary (idiopathic) or secondary (trauma during endoscopic retrograde cholangiopancreatography), and can lead to obstruction of bile and retrograde flow into the pancreatic parenchyma, causing inflammation.[30]

Patients with the familial form of pancreatitis present with abdominal pain early in childhood. The genetic defect appears to be transmitted as a non-X-linked dominant with variable penetrance and progress to chronic pancreatitis. Other conditions may be associated, such as diabetes mellitus or aminoaciduria.[5] Hereditary pancreatitis accounts for 1% of all cases, and several mutations have been described as possible inducers of the disease. The strongest correlations are with the cationic trypsinogen gene (PRSS1) on chromosome 7q35 and SPINK1 and CRTF gene mutations.[31][32][33] PRSS1 and chymotrypsin C mutations are strongly associated with early-onset pancreatitis.[34]

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