Biochemical events in peritoneal tissue repair.

Abstract

The increased incidence of postoperative adhesions and their complications have refocused attention on our understanding of adhesions, their clinical consequences and prevention. Postsurgical adhesions have four major negative impacts on health care outcomes. First, adhesions cause significant morbidity, including intestinal obstruction, infertility and pelvic pain. Second, adhesions are associated with multiple surgical complications. Third, these complications lead to greater surgical workload and utilization of hospital and other health care resources. Fourth, all these negative impacts result in significant economic burden to society. The complexities of adhesion formation and limitations in their understanding and research have hampered the development of satisfactory preventive treatments. Adhesions are highly differentiated, formed through an intricate process and associated with a complex organ, the peritoneum. The surface lining of the peritoneum is the key site in adhesion formation and prevention. Two unique properties of the peritoneal surface play key roles in these processes: its delicacy and its uniform, relatively rapid rate of re-epithelialization, irrespective of the size of injury. A suitable barrier that separates damaged peritoneal surfaces for the entire five to seven days of re-epithelialization is likely to prove effective in reducing adhesion formation. Postsurgical peritoneal repair begins with coagulation, which releases a variety of chemical messengers that bring about a cascade of events. Some of the principal cellular elements in this cascade are leukocytes, including polymorphonuclear neutrophils and macrophages, mesothelial cells, and fibrin. Following surgical injury, macrophages exhibit increased phagocytic, respiratory burst and secretory activity, and after day 5, are the major component of the leukocyte population. Macrophages also recruit new mesothelial cells onto the surface of the injury. These cells form small islands throughout the injured area which proliferate into sheets of mesothelial cells and accomplish re-epithelialization, usually five to seven days after surgical injury. The progenitor to adhesions is the fibrin gel matrix which develops in several steps. These include the formation and insolubilization of fibrin polymer and its interaction with fibronectin and a series of amino acids. Protective fibrinolytic enzyme systems of the peritoneal mesothelium, such as the tissue plasminogen activator (tPA) system, can remove the fibrin gel matrix. However, surgery dramatically diminishes fibrinolytic activity. This occurs in at least two ways: first, by increasing levels of plasminogen activator inhibitors and second, by reducing tissue oxygenation. Peritoneal re-epithelialization and adhesion formation thus can be seen as alternative pathways following peritoneal injury. The pivotal events determining the pathway are the apposition of two damaged surfaces and the extent of fibrinolysis. Development of strategies to separate damaged peritoneal surfaces and to foster an appropriate degree of fibrinolysis appears to be among the most promising avenues of adhesion prevention research. Hopefully, these efforts will lead to adhesion-free peritoneal healing following abdominal surgery.