Aetiology and epidemiology of acute pancreatitis

Gallstones and alcoholism together account for about 80% of acute pancreatitis worldwide. These and the other main causes of acute pancreatitis are listed in Table 25.1 (see also Boxes 25.1 and 25.2). Opie first pointed out the relationship between gallstones and pancreatitis in 1901 based on autopsy evidence. Small gallstones may cause transient obstruction as they pass through the ampulla via the bile ducts, or larger stones may impact at the lower end of the common bile duct, resulting in pancreatic duct obstruction. Beyond this, the precise mechanism of gallstone pancreatitis remains obscure.

The proportion of acute pancreatitis caused by alcoholism varies from country to country; for example, about two-thirds of patients in the UK have a gallstone aetiology whereas in parts of the USA and continental Europe about two-thirds have an alcohol aetiology. Longstanding high intake for at least 2 years is usually required to cause alcoholic pancreatitis; the mean daily intake of pure alcohol in subjects of one study was 140 g, compared with 40 g in controls. Occasionally acute pancreatitis can result from a single session of heavy drinking—students finishing exams beware! The mechanism of alcoholic pancreatitis is unknown but is probably the toxic effect of alcohol on the pancreas in genetically predisposed individuals.

In developed countries, the annual incidence of acute pancreatitis requiring hospital admission is about 1 : 2000 population and mortality is between 2% and 6%. About 15% fall into the category of severe pancreatitis. Women are affected more than men, but men are more likely to suffer recurrent attacks. The peak incidence is between 50 and 60 years. The reported incidence appears to have risen by a factor of 10 over the last 40 years, with only part of this attributable to improved diagnosis. Other factors are unknown.

Pathophysiology of acute pancreatitis

Acute pancreatitis is characterised by the sudden onset of diffuse inflammation of the pancreas. A range of diverse factors initiate disturbances of cellular metabolism, chiefly concerned with membrane stability. This leads to inappropriate activation of zymogens (pre-enzymes) within the pancreas. Activation of trypsin is probably the key initiating event and this overwhelms intrinsic antitrypsin activity, leading to interstitial oedematous pancreatitis. Fortunately, the extent and severity of inflammation remain mild and self-limiting in most patients and systemic effects are mild. In the least severe cases, there is minimal peritoneal exudation and no pancreatic changes detectable on contrast-enhanced CT scanning. In more severe disease, the pancreas becomes swollen and oedematous but remains viable. If laparotomy is inadvertently performed at this stage, clear, non-infected peritoneal fluid is found, with whitish patches on great omentum and mesentery representing areas of fat saponification (‘fat necrosis’). If it is extensive, calcium becomes sequestered in these areas and this is incriminated in the drop in blood calcium characteristic of severe acute pancreatitis.

As severity increases, trypsin and other enzymes cause increasingly extensive local damage as well as activation of complement and cytokine systems leading on to systemic inflammatory response syndrome (SIRS) and organ failure. Manifestations include shock, acute respiratory distress syndrome (ARDS), renal failure and disseminated intravascular coagulation (see Ch. 2). At this stage, acute peripancreatic fluid collections become detectable on CT. The most severe pancreatitis is associated with pancreatic necrosis. Ischaemia within the gland plus reperfusion injury are likely mechanisms in transforming acute oedematous pancreatitis into this necrotising disease. Complications are common and mortality in this group (even without infection) is as high as 10%.

A substantial proportion of these patients develop infection of the necrotic pancreas, usually with Gram-negative organisms translocated from bowel. This occurs within 2 weeks of the onset and greatly increases mortality. Pancreatic abscess formation is a different phenomenon, developing later and having a somewhat better prognosis.

In patients dying of acute necrotising pancreatitis, the peritoneal cavity becomes filled with dark, blood-stained inflammatory exudate containing fine lipid droplets. This is known as acute haemorrhagic pancreatitis. The peritoneal surface is grossly inflamed and semi-digested, and the pancreas is a necrotic mass.

Clinical features of acute pancreatitis (see Box 25.3)

Acute pancreatitis presents as a patient with an acute abdomen who has severe abdominal pain coming on suddenly and continuously from the outset. Initially it is poorly localised in the central and upper abdomen and is often described by the patient as ‘going through to the back’. Vomiting may be an early feature. In the early stages, the patient is restless and constantly changes posture in the search for a comfortable position. Pain is most often relieved by leaning forward in the ‘pancreatic position’. With the onset of chemical peritonitis, movement becomes increasingly painful and the patient lies very still. Clinical signs depend on the severity of the inflammatory process and the stage it has reached.