Cellular dysfunction in the pathogenesis of organ failure. New insights from molecular and cell biology

Multiple organ failure remains the major cause of death in critically ill p atients. In view of therapeutic strategies, current research activites focu s on the cellular response to different kinds of cellular stress (hypoxia, oxidative damage and mechanical distress) in the pathogenic sequelae of org an failure. The cellular stress reactions are characterized by induction of adaptive programs of gene expression (e.g. acute phase proteins, heat shoc k proteins, hypoxia-associated proteins) to protect the cells from energy d epletion and cell death. Generally, the mitochondria are early indicators o f cellular stress showing a loss of cytochrome c and a breakdown of the tra nsmembrane potential. Shortage of ATP and decrease of pH can be observed in the cytoplasm which leads to a disintegration of the cytoskeleton. As a co nsequence, the cell becomes spherical and separates from the surrounding ce lls. Depending on the acuity of the stressor the cell dies due to necrosis or apoptosis. Dysregulation of the balance of apoptosis and necrosis in dif ferent organs seems to be an important mechanism in the development of orga n failure. New insights into the cellular mechanisms during organ dysfuncti on promote the development of new diagnostic (e. g. optical and spectroscop ic) and pharmacological tools leading to a better prevention and therapy of organ failure.