ROLE OF THE GUT IN MULTIPLE ORGAN FAILURE - BACTERIAL TRANSLOCATION AND PERMEABILITY CHANGES

It is clear that increased gut permeability and bacterial translocatio n play a role in multiple organ failure (MOF). Failure of the gut barr ier remains central to the hypothesis that toxins escaping from the gu t lumen contribute to activation of the host's immune inflammatory def ense mechanisms, subsequently leading to the autointoxication and tiss ue destruction seen in the septic response characteristic of MOF. Howe ver, the role of the gut is more than that of a sieve, which simply al lows passage of bacteria and endotoxin from the gut lumen to the porta l or systemic circulation. It appears, in addition, that the transloca tion of bacteria, and endotoxin may lead to local activation of the im mune inflammatory system and the local production of cytokines and oth er immune inflammatory mediators. These intestinally derived mediators may then exacerbate the systemic inflammatory response and potentiall y lead to a further increase in gut permeability. A vicious cycle of i ncreased intestinal permeability, leading to toxic mediator release, r esulting in a further increase in gut permeability is generated. Addit ionally, the systemic and local inflammatory cells that become activat ed in the gut contribute to the systemic response characteristic of th e sepsis syndrome and MOF. Thus even if the immune inflammatory system , rather than the gut, is the ''motor of' MOF, the gut remains one of the major pistons that turns the motor.