Experimental evidence of obesity as a risk factor for severe acute pancreatitis

Abstract

The incidence of acute pancreatitis, an inflammation of the pancreas, is increasing worldwide. Pancreatic injury is mild in 80%-90% of patients who recover without complications. The remaining patients may develop a severe disease with local complications such as acinar cell necrosis, abscess and remote organ injury including lung injury. The early prediction of the severity of the disease is an important goal for physicians in management of patients with acute pancreatitis in order to optimize the therapy and to prevent organ dysfunction and local complications. For that purpose, multiple clinical scale scores have been applied to patients with acute pancreatitis. Recently, a new problem has emerged: the increased severity of the disease in obese patients. However, the mechanisms by which obesity increases the severity of acute pancreatitis are unclear. Several hypotheses have been suggested: (1) obese patients have an increased inflammation within the pancreas; (2) obese patients have an increased accumulation of fat within and around the pancreas where necrosis is often located; (3) increase in both peri- and intra-pancreatic fat and inflammatory cells explain the high incidence of pancreatic inflammation and necrosis in obese patients; (4) hepatic dysfunction associated with obesity might enhance the systemic inflammatory response by altering the detoxification of inflammatory mediators; and (5) ventilation/perfusion mismatch leading to hypoxia associated with a low pancreatic flow might reduce the pancreatic oxygenation and further enhance pancreatic injury. Recent experimental investigations also show an increased mortality and morbidity in obese rodents with acute pancreatitis and the implication of the adipokines leptin and adiponectin. Such models are important to investigate whether the inflammatory response of the disease is enhanced by obesity. It is exciting to speculate that manipulation of the adipokine milieu has the potential to influence the severity of acute pancreatitis.

Figure 1

Overview of the major events occurring in experimental acute pancreatitis and pancreatitis-associated lung injury. Inflammatory cells adhere to the endothelial walls via the expression of the intercellular molecules (ICAM-1) and translate the local inflammation to remote organs.

Figure 2

Mediators involved in the pathogenesis of acute pancreatitis. After the acinar cell injury occurs, inflammatory cells will synthesize and release proinflammatory cytokines and chemokines that induce systemic effects (vascular leakage, etc.). All these consequences will finally dictate the occurrence of pancreatic necrosis and abscess.