Acute pancreatitis is a medical emergency resulting from inflammation of the pancreas. It presents with the cardinal features of acute upper abdominal pain radiating to the back, elevated levels of the pancreatic enzymes amylase and lipase, and characteristic features on imaging. The mechanism involves premature activation of enzyme precursors in the acinar cells triggering an inflammatory cascade. The common associated causes are gall stones and alcohol abuse; the role of some other conventionally listed 'causes' as memorised by medical students is more controversial. Acute pancreatitis is self-limiting in about 80% of cases, and resolves with conservative management. More severe cases are associated with profuse fluid loss into the peritoneal cavity, shock, and development of renal and pulmonary problems. Haemorrhage and necrosis may produce extensive loss of pancreatic tissue, and secondary infection may develop as the result of invasion by gut bacteria. The mortality of acute pancreatitis is about 4–5%. Acute pancreatitis may sometimes occur as a manifestation of a chronic inflammatory process, or even pancreatic cancer, and may predispose to chronic pancreatitis. The pancreatic islets are relatively spared during acute pancreatitis, even when there is extensive damage to exocrine tissue, but acute hyperglycaemia develops in >50% and permanent diabetes in about 5% of patients.
The bile duct and main pancreatic duct meet at the sphincter of Oddi before emptying their contents into the small intestine. In 1856 Claude Bernard suggested that pancreatitis might be due to reflux of bile into the pancreatic duct. In 1901 Eugene Opie, the father of pancreatic pathology, described two patients in whom pancreatitis was due to blockage of the pancreatic duct by gall stones, and proposed that pancreatitis was caused by migration of gall stones down the bile duct.
Acute pancreatitis is of interest to diabetologists for three main reasons. First, because it may be a cause of diabetes. Second, because people with type 2 diabetes may be at increased risk of acute pancreatitis. Third, because acute pancreatitis has been associated with glucagon-like peptide-1 (GLP-1)-based therapies.
This section considers acute pancreatitis as a cause of diabetes.
There are about 200,000 cases each year in the USA, and the incidence of acute pancreatitis is estimated at 35–45 per 100,000 per year in California and rising. A rising incidence has also be reported in Europe. The incidence may vary from one population to another in proportion to obesity (predisposing to gallstones), alcohol consumption and possibly ethnicity.
The diagnosis of acute pancreatitis is based upon the triad of symptoms, enzyme elevation and radiological signs. Severe cases are readily diagnosed, but the diagnosis may be open to differences of clinical interpretation at the milder end of the spectrum, thus complicating estimates of its incidence.
Acute pancreatitis typically presents with severe upper abdominal pain radiating through to the back and prostration. On palpation the abdomen shows tenderness but not rigidity (sometimes referred to as the 'platonic love' sign). Severe cases present with hypotension and shock, and various surgical scales have been devised to assess the severity and prognosis of the condition.
The pancreatic enzymes amylase and lipase are released in the circulation, and a rise in amylase to three times the upper limit of normal supports a diagnosis of acute pancreatitis.
Contrast-enhanced computerised tomography (CT) may be used to confirm the diagnosis, and is reported to have about 90% sensitivity and specificity in this role.
The bile duct and main pancreatic duct join at the ampulla of Vater, where their contents are released concurrently into the second part of the duodenum. The rate of release is regulated by a muscular sphincter known as the sphincter of Oddi. This anatomical arrangement has the disadvantage that it permits reflux of bile into the pancreatic duct should the main outlet become obstructed, for example by a gallstone.
The exocrine pancreatic enzymes required for digestion are produced in the acinar cells where they are stored in cytoplasmic zymogen granules. The granules accumulate near the cell apex and are released by exocytosis. The acinar cells are arranged in secretory acini which drain first into intercalated ducts, thence into interlobular ducts and finally into the main pancreatic duct .
Pancreatic enzymes such as trypsinogen are synthesised and stored in an inactive – hence harmless – form, and are activated upon release into the lumen of the duodenum via the action of enterokinases. Premature activation of these enzyme precursors results in autodigestion of the surrounding tissues and triggers an inflammatory chain response.
Premature activation may occur for a variety of reasons. A genetic defect is responsible for the rare condition of hereditary pancreatitis, and some toxins have been implicated in animals and humans. The leading cause, however, appears to be obstruction resulting in increased back-pressure within the acini.
Obstruction appears to be an important element in pancreatitis secondary to gallstones or arising in relation to chronic pancreatitis or pancreatic carcinoma. Cannulation of the pancreatic or bile ducts in the course of endoscopic retrograde cholangiopancreatography (ERCP) may also provoke episodes of acute pancreatitis. Other functional changes that might allow reflux of blie acids or bacteria into the pancreatic duct have been postulated, such as sphincter of Oddi dysfunction, but these are more controversial.
Causes of acute pancreatitis
- Toxic, e.g. alcohol, organophosphate insecticides
- Surgical manipulation, e.g ERCP
- Infective, e.g. mumps
- Metabolic, e.g. hypercalcaemia
No defined cause can be assigned in about 20% of patients.
The traditional list of 'causes' of acute pancreatitis is unsatisfactory for a number of reasons. This is mainly because of the absence of a clear mechanism for non-obstructive causes, which might therefore be better considered as predisposing factors.
The role of alcohol consumption, for example, remains somewhat uncertain, although possibly mediated by the effect of alcohol upon cholecystokinin, which causes increased motility of the gall bladder and hypersecretion of both bile and pancreatic juices.
Diabetes secondary to acute pancreatitis
The islets are surprisingly well preserved in acute pancreatitis. For example, it was established before the discovery of insulin that diabetes was not induced by tying off the pancreatic duct of an experimental animal (and thus inducing autodigestion of the gland). Banting's first idea about extracting insulin was based on this observation, on the assumption that this hypothetical hormone would be destroyed by pancreatic enzymes if he attempted extraction from a healthy pancreas.
It follows from the above that diabetes usually results from severe or haemorrhagic pancreatitis resulting in loss of most of the exocrine tissue, and is therefore associated with extensive loss of pancreatic islet cells, including the glucagon-secreting islet cells, and with exocrine pancreatic deficiency.
Management is by removal of possible precipitating causes, for example by cholecystectomy if gallstones are present, by alcohol avoidance in heavy drinkers, or by stopping prescription of drugs suspected to cause pancreatitis.
Exocrine pancreatic failure is treated by taking pancreatic enzyme preparations by mouth whenever food is consumed. Insulin is often needed for metabolic control, but small doses are generally effective because its action is not balanced by secretion of pancreatic glucagon, and there is an increased risk of hypoglycaemia. Late complications may develop, and the prognosis is good provided that predisposing causes, such as heavy alcohol consumption, can be avoided.
^ Frossard J-L et al. Acute pancreatitis. Lancet 2008;371:143–52