title: Metabolism of sepsis and multiple organ failure.
abstract: "Septic autocannabalism" been coined to describe the metabolic response that follows severe sepsis in humans. The normal protein- and energy-conserving mechanisms evoked during simple starvation are not observed following the onset of sepsis. The metabolic response to sepsis entails rapid breakdown of the body's reserves of protein, carbohydrate, and fat. Hyperglycemia with insulin resistance, profound negative nitrogen balance, and diversion of protein from skeletal muscle to splanchnic tissues are prominent features. These responses are believed to be mediated in large part by inflammatory cytokines such as tumor necrosis factor alpha (TNFalpha), interleukin 1beta (IL-1beta), and IL-6. Secondary induction of catecholamines, cortisol, and glucagon by cytokines is likely to be another important effector mechanism. Infection and inflammation elicit a complex network of interwoven responses, and no single mediator alone accounts for the responses observed. Sepsis also commonly involves alterations in cardiovascular function with altered flow to key metabolic sites, hypoxia, damage to the gut's mucosal barrier, secondary organ failure, and alterations in capillary permeability. These structural and functional alterations also strongly influence the metabolic profile during infection. If these catabolic responses persist for more than a few days, severe malnutrition results and is likely to be an important risk factor for mortality in these patients. The altered metabolic milieu during sepsis prevents effective use of exogeneously delivered glucose and protein; at best, administration of these agents ameliorates but does not prevent the persistence of catabolism. Delivery of agents that antagonize cytokines and other moieties such as glutamine and growth hormone may, in the future, help to restore nitrogen balance during sepsis.
authors.affiliation: Bolton Hospitals NHS Trust and the North Western Injury Research Center, Manchester University, Manchester, U.K.
authors.forename: H R
authors.initials: HR
authors.lastname: Michie
mesh_terms: D000818:Animals; D003422:Critical Care; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000502:physiology; D009102:Multiple Organ Failure / Q000503:physiopathology* / Q000628:therapy; D010289:Parenteral Nutrition, Total; D011379:Prognosis; D011502:Protein-Energy Malnutrition / Q000503:physiopathology / Q000628:therapy; D012772:Shock, Septic / Q000503:physiopathology* / Q000628:therapy; D018746:Systemic Inflammatory Response Syndrome / Q000503:physiopathology* / Q000628:therapy
chemical_list: D018836:Inflammation Mediators