Molecular biology of multiple organ dysfunction syndrome: injury, adaptation, and apoptosis.
Injury will equal or surpass communicable disease in the year 2020 as the number one cause of lost disability-adjusted life-years worldwide. The major cause of "late death" after trauma is organ dysfunction, commonly as a complication of shock or sepsis. The pathophysiology of injury-induced organ dysfunction is poorly characterized but has been linked to systemic inflammation as a result of infection (either obvious or occult) or massive tissue injury (systemic inflammatory response syndrome, SIRS). Subsequent complications of organ dysfunction, including death, may also stem from immunosuppression characteristic of what has been called the counter-regulatory anti-inflammatory response syndrome (CARS). At the cellular level, injurious stimuli trigger adaptive stress responses that include changes in gene expression. Multiple organ dysfunction syndrome (MODS) is the summation of these stress responses to severe systemic injury, integrated at the cellular, organ, and host levels. We hypothesize that a complete understanding at the molecular level of the stress responses induced by injury will aid in the development of therapeutic strategies for treating MODS in the critically ill surgical patient. This paper reviews recent data from our Cellular Injury and Adaptation Laboratory relevant to our understanding of MODS pathophysiology, particularly as it relates to stress-induced cell death by apoptosis. Our data suggest that inhibition of stress-induced apoptosis may improve survival after severe injury.
Cobb
J P
JP
Cellular Injury and Adaptation Laboratory, Washington University School of Medicine, St. Louis, MO 63110, USA.
Buchman
T G
TG
Karl
I E
IE
Hotchkiss
R S
RS
D000220:Adaptation, Biological; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D009102:Multiple Organ Failure / Q000209:etiology* / Q000503:physiopathology*; D013312:Stress, Physiological / Q000150:complications / Q000503:physiopathology*; D014947:Wounds and Injuries / Q000150:complications / Q000503:physiopathology*