The liver as first target in multi-organ failure - pathophysiological aspects and therapy

Multi-organ failure (MOF) continues to be the major cause of death in criti cally iii patients. The impairment of organ function is induced by a system ic inflammatory response (SIRS). Changes in haemodynamics during SIRS influ ence the barrier function of the gut resulting in bacteraemia and endotoxae mia. The liver is the first target of invading bacteria and toxins which wi ll be detoxified by liver macrophages. Furthermore, a various number of med iators are released from liver macrophages aggravating microcirculatory dis turbances and activating other cells with immunological functions not only in the liver, but also in other organs especially in the lung. Alveolar mac rophages are primed by the liver derived mediators to react excessively to toxins and bacteria resulting in the release of vasoactive substances and l ytic enzymes which contribute to pulmonary vascular dysfunction followed by pulmonary hypertension and increased vascular permeability. Mediator induc ed alterations of liver function were also observed. Activated granulocytes release toxic oxygen radicals and lysosomal proteases in close contact wit h the endothelium causing tissue damage and impairment of liver function as assessed by increased serum bilirubin levels. Since liver failure is assoc iated with a high mortality, therapeutic strategies focus on the maintenanc e of an adequate perfusion of the liver and the gut. Many studies demonstra te, that an impairment of the microcirculation can persist even after the n ormalization of the systemic circulation by volume resuscitation. New exper imental strategies focus on the, antagonism of local active mediators such as endothelin, eicosanoids, NO, and CO, but further experimental and clinic al studies are necessary to evaluate these therapeutic approaches.