Acute lung injury and ARDS in acute pancreatitis: mechanisms and potential intervention

Abstract

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in acute pancreatitis still represents a substantial problem, with a mortality rate in the range of 30%-40%. The present review evaluates underlying pathophysiological mechanisms in both ALI and ARDS and potential clinical implications. Several mediators and pathophysiological pathways are involved during the different phases of ALI and ARDS. The initial exudative phase is characterized by diffuse alveolar damage, microvascular injury and influx of inflammatory cells. This phase is followed by a fibro-proliferative phase with lung repair, type II pneumocyte hypoplasia and proliferation of fibroblasts. Proteases derived from polymorphonuclear neutrophils, various pro-inflammatory mediators, and phospholipases are all involved, among others. Contributing factors that promote pancreatitis-associated ALI may be found in the gut and mesenteric lymphatics. There is a lack of complete understanding of the underlying mechanisms, and by improving our knowledge, novel tools for prevention and intervention may be developed, thus contributing to improved outcome.

Figure 1

The acute phase response as seen in critical illness, e.g. severe acute pancreatitis.

Figure 2

Course of acute pancreatitis. A potential development in severe acute pancreatitis with the first “insult” resulting in a pronounce systemic inflammatory response and potential development of organ dysfunction, and in the worst scenario early mortality. Later during the course, combination of organ dysfunction and infection, potentially pronounced after the second “insult” (translocation from the gut, burst of proinflammatory cytokines, surgery, etc.) may result in late mortality. MODS: Multiple organ dysfunction syndrome.

Figure 3

Acute pancreatitis-associated acute lung injury (ALI) - potential mechanisms including endothelial barrier dysfunction. Several adhesion molecules [selectins, intercellular adhesion molecule-1 (ICAM-1), platelet endothelial cell adhesion molecule-1 (PECAM-1) among others] involved in the extravasation of not at least polymorphonuclear neutrophils (PMNs). Tissue injury by not at least these PMNs.

Figure 4

Gut barrier failure. The increase in permeability of the gut barrier from the intestinal lumen may allow translocation of endotoxin and bacteria and there is also activation of immunocompetent cells in the gut wall and gut associated lymphoid tissue, contributing to the inflammatory response, infection, and potentially the development of organ dysfunction.