Page 22 - Postoperative Intra-Abdominal Adhesions- New insights in prevention and consequences

Chapter 2
serosanguinous exudate and a growth response by the mesothelial cells [8, 9]. Simultaneously with the inflammatory reaction the expression of tissue factor (TF) is up-regulated by macrophages and mesothelial cells. This causes activation of the extrinsic pathway of the coagulation cascade, eventually leading to the formation of a fibrinous exudate [10]. This process is called fibrinogenesis and is, just like inflammation, a physiological response to tissue injury and it is essential for normal wound healing in order to regain tissue strength (scar formation).
The formation of fibrin leads to the physiological process of fibrinolysis, the counterpart of fibrinogenesis, in order to resolve fibrin and prevent excessive formation of scar tissue [4]. It is initiated by the conversion of plasminogen to plasmin and driven by tissue-type plasminogen activator (tPA) and urokinase-like plasminogen activator (uPA), while in turn tPA is inhibited by plasminogen inhibitor-1 (PAI-1) in order to keep the balance [10]. tPA and uPA are expressed in endothelial cells, mesothelial cells and macrophages and tPA is responsible for 95% of the plasminogen conversion in the abdominal cavity. Plasmin is highly effective in degradation of fibrin and fibrin degradation products consequently playing an important role in prevention or arising of abdominal adhesions [11].
Whether surgical trauma results in adhesion formation or not depends on the balance between fibrinogenesis and fibrinolysis. After minimal injury to the peritoneum the fibrinolytic capacity will be large enough to resolve fibrin and its related products resulting in adhesion-free healing. Nevertheless, more severe surgical trauma leads to loss of mesothelial integrity and exposure of the underlying connective tissue resulting in a dramatical diminishing of the fibrinolytic capacity in the first 48 hours after the operation (Figure 1)[12, 13]. Consequently the fibrin deposits are not resolved and start to organize into fibrous adhesions due to ingrowth of fibroblasts and endothelial cells which is followed by capillary formation and incorporation of collagen, all stimulated by cytokines and growth factors (day 4 to 10)[10, 14].
20