Etiology

Gallstones and alcohol misuse account for at least half of cases of acute pancreatitis.[15][16][17] Hypertriglyceridemia and pancreatic tumors account for a much smaller number of cases. Determining the etiology is important to prevent a recurrence. Many patients have an initial attack of mild disease only to suffer a recurrence of acute pancreatitis within a year after discharge, and these patients may suffer a more severe form of the disease, such as pancreatic necrosis, organ failure, and/or death. Patients with hypertriglyceridemia and alcohol use disorder may benefit from treatment to reduce the risk of recurrent disease. Serum triglyceride should be obtained from patients found to have acute pancreatitis. If the triglyceride is over 1000 mg/dL, this should be considered causative.

While most patients with acute pancreatitis have a history of alcohol misuse, gallstones, hypertriglyceridemia, or pancreatic malignancy, the etiology remains elusive in approximately one third of patients.[14]​ These cases are often labeled "idiopathic". The presence of microlithiasis or biliary sludge accounts for many patients thought to have idiopathic pancreatitis. Any person over the age of 40 years thought to have idiopathic pancreatitis should be re-imaged on an outpatient basis (e.g., after 4-6 weeks) to rule out a tumor (magnetic resonance cholangiopancreatography preferred).[8][18]

Other causes include:

  • Hypercalcemia

  • Post-endoscopic retrograde cholangiopancreatography (2% to 3%)

  • Trauma

  • Infections (mumps, mycoplasma, Epstein-Barr virus, Ascaris lumbricoides, HIV-related coinfections)

  • Drugs[19][20]

  • Autoimmune conditions (collagen vascular diseases)

  • Pancreas divisum

  • Intraductal papillary mucinous neoplasm

  • Sphincter of Oddi dysfunction

  • Heredity[4][9]

  • Autoimmune (immunoglobulin G4-related) sclerosing acute pancreatitis

Clinicians should be wary of attributing acute pancreatitis to rare causes described in case reports when substantive evidence is lacking, and other factors may be involved. For example, the congenital abnormality pancreas divisum is seen in 10% to 15% of normal people and was not shown to increase the risk of acute pancreatitis in large population-based observational studies. However, genetic anomalies may explain why certain patients with pancreas divisum develop acute pancreatitis while others do not.[21]

While there is evidence from randomized trials that 6-mercaptopurine and azathioprine may cause acute pancreatitis, many other medications linked with acute pancreatitis are only described in case reports and lack high-quality evidence to support an association.[22][23][24]

Pathophysiology

The exact mechanism by which pancreatitis occurs is unknown, although there is evidence to suggest that abnormal intracellular calcium accumulation is an important step in the molecular pathophysiology of acute pancreatitis development. Increased calcium transients potentiate colocalization of zymogen and lysosome granules and ultimately lead to premature enzymatic activation.[25]

Ethanol-induced pancreatitis has different pathophysiologic mechanisms. Studies have described that ethanol is a direct toxic insult to the acinar cell, causing inflammation and membrane destruction. Other mechanisms include sphincter of Oddi dysfunction, induction of hypertriglyceridemia, or formation of free oxygen radicals.[26] Some studies have demonstrated that ethanol causes an increase in ductal pressures secondary to protein deposition within the pancreatic duct, favoring retrograde flow and intrapancreatic enzymatic activation.[1]

Classification

Revised Atlanta classification[2]

The revised classification of acute pancreatitis identifies an early and a late phase of the disease. Severity is classified as mild, moderate, or severe.[2]

  • Mild acute pancreatitis: the most common form, has no organ failure or local or systemic complications, and usually resolves in the first week.

  • Moderately severe acute pancreatitis: presence of transient organ failure (resolves within 48 hours), and/or local complications or exacerbation of comorbid disease.

  • Severe acute pancreatitis: persistent organ failure (>48 hours). Local complications are common and include peripancreatic fluid collections, pancreatic and peripancreatic necrosis (sterile or infected), pseudocyst, and walled-off necrosis (sterile or infected).

Balthazar classification

This is a radiologic classification typically based on computed tomography with intravenous contrast, which focuses on the extent of pancreatic inflammation and the presence or absence of fluid collections or gas suggestive of necrosis.[3]

  • A: Normal

  • B: Focal or diffuse gland enlargement; small intrapancreatic fluid collection

  • C: Any of the above plus peripancreatic inflammatory changes and <30% gland necrosis

  • D: Any of the above plus single extrapancreatic fluid collection and 30% to 50% gland necrosis

  • E: Any of the above plus extensive extrapancreatic fluid collection, pancreatic abscess, and >50% gland necrosis

General pathologic classification

Surgical textbooks often distinguish between edematous and hemorrhagic pancreatitis, based on pathologic/histologic features:

  • Edematous pancreatitis: pancreatic parenchyma and surrounding retroperitoneal structures are engorged with interstitial fluid and infiltration of inflammatory cells.[4][5]

  • Hemorrhagic pancreatitis: bleeding into the parenchyma and surrounding retroperitoneal structures with extensive pancreatic necrosis.[4][5]

The utility of this classification system in the clinical setting is unclear. The treatment of hemorrhage in patients with pancreatitis varies and depends on the cause (e.g., pseudoaneurysm, pancreatic necrosis, hemosuccus pancreaticus, or other gastrointestinal bleeding). For this reason, the term "hemorrhagic pancreatitis" should be avoided in the acute management setting.

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