Protein Anabolism in Critically Ill Children: Pathophysiological aspects and interventional challenges

Critical illness can be defi ned as “a life threatening medical or surgical condition usually requiring intensive care unit (ICU) level care“ [1]. It mostly results from infection, sepsis and trauma (including surgery and burns). Th ese conditions are accompanied by similar physiological and biochemical responses, which have been termed the systemic infl ammatory response syndrome (SIRS) [2]. Th e associated major metabolic changes are also known as the acute stress response. From an evolutionary point of view these responses are required for the “fi ght, fl ight, fright” reaction when encountering a thread, to mobilise fuels for tissues that are activated [3-5]. A key feature is increased sympathetic nervous system activity, resulting in increased levels of adrenaline and glucocorticoids. Subsequently, immune cells are activated and pro-infl ammatory cytokines secreted, which trigger further metabolic changes. In addition, insulin secretion is increased as well as the counter regulatory hormones glucagon, cathecholamines, cortisol and growth hormone. As a result, glucose production is increased via increased glycogenolysis and gluconeogenesis and insulin resistance develops, leading to hyperglycemia. Also, fat is mobilised (lipolysis) and fat oxidation and ketone body formation are increased, while muscle protein breakdown is stimulated to provide amino acids for protein synthesis in proliferating cells, the production of acute phase proteins and other peptides (e.g. cytokines) and for gluconeogenesis. Th us, protein turnover is increased, with both increased protein breakdown and protein synthesis. Protein synthesis, however, is stimulated to a lesser extent than protein breakdown, resulting in net protein loss, i.e. protein catabolism. In addition, the increased substrate cycling results in increased energy expenditure, because both protein synthesis and breakdown consume ATP.

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