CLINICAL-SIGNIFICANCE OF TRANSLOCATION

The gastrointestinal tract, besides being the organ responsible for nu trient absorption, is also a metabolic and immunological system, funct ioning as an effective barrier against endotoxin and bacteria in the i ntestinal lumen. The passage of viable bacteria from the gastrointesti nal tract through the epithelial mucosa is called bacterial translocat ion. Equally important may be the passage of bacterial endotoxin throu gh the mucosal barrier. This article reviews the evidence translocatio n of both endotoxin bacteria is of clinical significance. It summarise s recent published works indicating that translocation of endotoxin in minute amounts is a physiological important phenomenon to boost the r eticuloendothelial system (RES), especially the Kupffer cells, in the liver. Breakdown of both the mucosal barrier and the RES capacity resu lts in systemic endotoxaemia. Systemic endotoxaemia results in organ d ysfunction, impairs the mucosal barrier, the clotting system, the immu ne system, and depresses Kupffer cell function. If natural defence mec hanisms such as lipopolysaccharide binding protein, high density lipop rotein, in combination with the RES, do not respond properly, dysfunct ion of the gut barrier results in bacterial. translocation. Extensive work on bacterial translocation has been performed in animal models an d occurs notably in haemorrhagic shock, thermal injury, protein malnut rition, endotoxaemia, trauma, and intestinal obstruction. It is diffic ult to extrapolate these results to humans and its clinical significan ce is not clear. The available data show that the resultant infection remains important in the development of sepsis, especially in the crit ically ill patient. Uncontrolled infection is, however, neither necess ary nor sufficient to account for the development of multiple organ fa ilure. A more plausible sequelae is that bacterial translocation is a later phenomenon of multiple organ failure, and not its initiator. It is hypothesised that multiple organ failure is more probably triggered by the combination of tissue damage and systemic endotoxaemia. Endoto xaemia, as seen in trauma patients especially during the first 24 hour s, in combination with tissue elicits a systemic inflammation, called Schwartzmann reaction. Interferon gamma, a T cell produced cytokine, i s thought to play a pivotal part in the pathogenesis of this reaction. This reaction might occur only if the endotoxin induced cytokines lik e tumour necrosis factor and interleukin 1, act on target cells prepar ed by interferon gamma. After exposure to interferon gamma target cell s become more sensitive to stimuli like endotoxin, thus boosting the i nflammatory cycle. Clearly, following this line of reasoning, minor ti ssue damage or retroperitoneal haematoma combined with systemic endoto xaemia could elicit this reaction. The clinically observed failure of multiple organ systems might thus be explained by the interaction of t issue necrosis and high concentrations of endotoxin because of translo cation. Future therapeutic strategies could therefore focus more on bi nding endotoxin in the gut before the triggering event, for example be fore major surgery. Such a strategy could be combined with the start o f early enteral feeding, which has been shown in animal studies to hav e a beneficial effect on intestinal mucosal barrier function and in tr aumatised patients to reduce the incidence of septic complications.