Pathophysiology of Acute Pancreatitis

Abstract

The vast majority of patients with acute pancreatitis either have gallstones or drink too much alcohol. While little is known about the action of ethanol on the exocrine pancreas, the mechanisms involved in gallstone-induced pancreatitis have recently been elucidated to an extent that allows conclusions about the pathophysiology of pancreatitis. In the following review article we will discuss the clinical and experimental studies which have shaped our understanding of biliary pancreatitis. While most of the questions regarding the association of gallstones and pancreatitis appear to be resolved, the intracellular alterations which immediately follow these triggering events and ultimately lead to acinar cell necrosis are less well understood. These early pathophysiological changes within the pancreas have been the target of an intense research interest and the subject of sometimes equally passionate controversies. We will discuss the studies that have addressed the premature and intracellular activation of digestive enzymes in acute pancreatitis and review some of the current theories and arguments which attempt to confront this issue.

Role of cathepsin B in intracellular trypsinogen activation and the onset of acute pancreatitis

“…This view has not changed, and according to our current understanding, the onset of the disease involves a premature and intrapancreatic activation of proteolytic enzymes (2). Digestive proteases are, however, synthesized and secreted as inactive precursor zymogens, and the pancreatic acinar cell possesses a whole variety of protective mechanisms that either prevent premature zymogen activation or inhibit protease activity (41). The question, therefore, remains as to which molecular factors either trigger the initial protease activation or permit the cellular defenses to be overcome.…”

Metabolic Management of Severe Acute Pancreatitis

“…It has been proposed that an apical exocrine secretory block is the common pathway in the pathogenesis of pancreatitis [6]. This block is probably the result of microtubular dysfunction, which can result from oxidative stress [7][8][9]. Continued zymogen synthesis and intracellular transport results in an accumulation within the cell.…”

The Role of Surgery in the Management of Acute Pancreatitis

“…There is strong circumstantial evidence that stones in the distal common duct cause pancreatitis when they temporarily obstruct the pancreatic duct orifice at the ampulla of Vater. Despite many efforts, however, it is still uncertain how these stones actually cause the pancreatic inflammation (7).…”