title: Hypermetabolism/organ failure: the role of the activated macrophage as a metabolic regulator.
abstract: Multiple organ failure continues as the main cause of death after burns, trauma and sepsis. This clinical syndrome represents the transition from a hypermetabolic response to injury to a setting of clinical organ failures and death. Risk factors include: perfusion deficits, persistent foci of dead or injured tissue, an uncontrolled focus of infection, the presence of the respiratory distress syndrome, persistent hypermetabolism, and preexisting fibrotic liver disease. Once in the organ failure syndrome, most treatment modalities become progressively ineffective, including: ventilation, antibiotics, nutrition, and surgery. The best treatment remains prevention with rapid control of the source and restoration of oxygen transport. The response to injury involves alterations in physiology and in the metabolism of carbohydrate, fat and amino acids. These changes seem to reflect the modulation of the end-organs by the mediator systems activated in response to the stress stimulus. The transition from hypermetabolism to organ failure appears to reflect the clinical appearance of liver failure. It is currently hypothesized that this liver failure represents a state of regulatory dysfunction induced by the activated hepatic macrophage, the Kupffer cell. This same process may also influence metabolic failure in other organs where this cell-cell regulation can occur, e.g. kidney, lung. The activation of these macrophages is hypothesized to represent the final stage of a series of continuous stimulating events, eg. hypoxia, endotoxin, bacteria, and gut translocated toxins. The precise monokine(s) responsible are not yet completely characterized. Treatment consists of the modalities outlined above and the employment of aggressive metabolic (nutritional) support.
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis 55455.
authors.forename: F B
authors.initials: FB
authors.lastname: Cerra
authors.forename: M
authors.initials: M
authors.lastname: West
authors.forename: G
authors.initials: G
authors.lastname: Keller
authors.forename: J
authors.initials: J
authors.lastname: Mazuski
authors.forename: R L
authors.initials: RL
authors.lastname: Simmons
mesh_terms: D006801:Humans; D007728:Kupffer Cells / Q000502:physiology; D008099:Liver / Q000473:pathology / Q000503:physiopathology; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D008660:Metabolism; D009102:Multiple Organ Failure / Q000503:physiopathology*