Cellular energetic metabolism in sepsis: the need for a systems approach.
Sepsis is a complex pathophysiological disorder arising from a systemic inflammatory response to infection. Patients are clinically classified according to the presence of signs of inflammation alone, multiple organ failure (MOF), or organ failure plus hypotension (septic shock). The organ damage that occurs in MOF is not a direct effect of the pathogen itself, but rather of the dysregulated inflammatory response of the patient. Although mechanisms underlying MOF are not completely understood, a disruption in cellular energetic metabolism is increasingly implicated. In this review, we describe how various factors affecting cellular ATP supply and demand appear to be altered in sepsis, and how these vary through the timecourse. We will emphasise the need for an integrated systems approach to determine the relative importance of these factors in both the failure and recovery of different organs. A modular framework is proposed that can be used to assess the control hierarchy of cellular energetics in this complex pathophysiological condition.
Carré
Jane E
JE
Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK. j.carre@ucl.ac.uk
Singer
Mervyn
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D001831:Body Temperature; D004734:Energy Metabolism; D006339:Heart Rate; D006801:Humans; D000860:Hypoxia / Q000209:etiology / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D009102:Multiple Organ Failure / Q000378:metabolism / Q000503:physiopathology; D010101:Oxygen Consumption; D018805:Sepsis / Q000378:metabolism* / Q000503:physiopathology; D012772:Shock, Septic / Q000378:metabolism / Q000503:physiopathology
D000255:Adenosine Triphosphate