Acute pancreatitis : epidemiology and relationship to amylin

Abstract

Aims: i) To review the epidemiological literature of acute pancreatitis; ii) To analyse the epidemiology of acute pancreatitis in South Auckland, New Zealand; iii) To investigate experimentally the relationship between pancreatic perfusion, the endocrine pancreas, amylin, the intestine and the pathogenesis of acute pancreatitis Methods and Results: Epidemiological studies of acute pancreatitis from 1960 - 2000 were comprehensively reviewed. This was followed by an audit of all patients admitted with acute pancreatitis between 1995-1997 to Middlemore hospital, South Auckland. There were 257 'first-time attacks'. They comprised 52 (20 %) 'Maori', 40 (16 %) 'Pacific' and 165 'Other" (equivalent to European) cases. Maori had higher age-standardised incidence rates (46.0 per 100,000 person yrs) compared to Pacific (35.7) and Other (19.1). The highest rates were in Maori females (59.7). Symptoms, aetiological distribution, severity and case fatality were similar between the ethnic groups. The initial clinical study found circulating amylin concentrations were increased in patients developing severe pancreatitis compared to those with mild disease and normals. Subsequent experimental evidence demonstrated that circulating amylin concentration in the rat was increased by pancreatitis as well as after independent intestinal ischaemiareperfusion injury (severity dependent). Exogenous amylin was found to be more vasoactive in the pancreas than the intestine where it acted to decrease pancreatic perfusion at the microvascular level (laser Doppler flowmetry) but to cause an overall vasodilatation in larger resistance vessels (isolated perfused pancreas model). Both these vascular effects were dose-dependent. It was also discovered that pancreatitis, intestinal ischaemia and pH changes each uniquely altered amylin and insulin circulating concentrations or secretion, suggesting dissociation of the normal co-secretory behaviour. The addition of exogenous rat amylin to a background of established mild pancreatis caused gastric stasis, hypocalcaemia and hypochloraemic metabolic alkalosis but no significant detectable alteration in pancreatitis histological severity. Conclusions: The epidemiological study found acute pancreatitis was common by international standards in South Auckland and particularly in Maori. The actions of amylin on systemic physiology as well as on the pancreatic microcirculation make it a novel candidate for further investigation into the role of islet hormonal products may play in the pathogenesis of acute pancreatitis.