Aetiology

Gallstones and alcohol misuse account for at least half of cases of acute pancreatitis.[14][15] Aetiology remains elusive in approximately one third of patients.[13][16] These cases are often labelled 'idiopathic', although the presence of microlithiasis or biliary sludge accounts for many patients thought to have idiopathic pancreatitis.[17] In the UK, around 50% of cases are caused by gallstones, 25% by alcohol, and 25% by other factors.[8] The most common cause worldwide is alcohol consumption. 

Hypertriglyceridaemia and pancreatic malignancy account for a much smaller number of cases but are important causes to exclude. Patients with hypertriglyceridaemia may benefit from treatment to reduce the risk of recurrent disease. Consider pancreatic cancer in any person over the age of 40 thought to have idiopathic pancreatitis; these patients should be re-imaged after the acute episode has resolved.[18][19]

Other causes include:

  • Hypercalcaemia

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

  • Trauma

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

  • Drugs (e.g., azathioprine, mercaptopurine); there are limited data to support a causative role for other drugs that have been implicated (e.g., furosemide, oestrogens, thiazide diuretics, sulfonamides, tetracyclines, sulindac, valproate, and L-asparaginase)[17][18][20][21][22]

  • 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.

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.[23]

While there is evidence from randomised trials implicating a small number of specific drugs in acute pancreatitis, many other medications linked with acute pancreatitis are only described in case reports and lack high-quality evidence to support an association.[24][25]

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 co-localisation of zymogen and lysosome granules and ultimately lead to premature enzymatic activation.[26]

Ethanol-induced pancreatitis has different pathophysiological 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 hypertriglyceridaemia, or formation of free oxygen radicals.[27] Some studies have demonstrated that ethanol causes an increase in ductal pressures secondary to protein deposition within the pancreatic duct, favouring retrograde flow and intra-pancreatic 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 peri-pancreatic fluid collections, pancreatic and peri-pancreatic necrosis (sterile or infected), pseudocysts, and walled-off necrosis (sterile or infected).

Balthazar classification

This is a radiological 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 intra-pancreatic fluid collection

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

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

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

General pathological classification

Surgical textbooks often distinguish between oedematous and haemorrhagic pancreatitis, based on pathological/histological features:

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

  • Haemorrhagic 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 haemorrhage in patients with pancreatitis varies and depends on the cause (e.g., pseudoaneurysm, pancreatic necrosis, haemosuccus pancreaticus, or other gastrointestinal bleeding). For this reason, avoid the term 'haemorrhagic pancreatitis' in the acute management setting.

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