Author:

Keywords:

Critical illness, Muscle weakness, Muscle atrophy, Myopathy, Ubiquitine-proteasome system, Autophagy, Nutrition

Abstract:

© Springer Science+Business Media New York 2015. Muscle weakness develops in a substantial proportion of critically ill patients. The consequences are severe, as illustrated by a prolonged dependency on mechanical ventilation and intensive care, impaired rehabilitation, and increased risk of death. Muscle weakness may originate from neurogenic disturbances, myogenic disturbances, or a combination of both.Regarding the myogenic component of muscle weakness, loss of muscle mass or atrophy has classically been put forward as culprit, whereas the importance of muscle quality has long been underappreciated and only recently has gained attention. Muscle atrophy of critical illness develops due to a decreased synthesis and accelerated breakdown of myofibrillar proteins. Several proteolytic systems are activated, including the ubiquitin-proteasome pathway, calpains, and lysosomal proteases. Also excessive activation of autophagy, which is a highly specialized lysosomal degradation pathway with a crucial role in intracellular quality control, has been implicated in the aggravation of muscle loss. Nevertheless, recent studies suggest that impairment of autophagy jeopardizes muscle quality and function and that autophagy may be insufficiently activated during critical illness.Illness-associated anorexia and gastrointestinal dysfunction often lead to a severe caloric deficit, which contributes to muscle atrophy.This raised the hypothesis that preventing the caloric deficit with intravenous nutrition would attenuate muscle atrophy and weakness. However, such nutritional interventions failed to prevent severe muscle atrophy. Recent studies pinpoint two potential explanations for the lack of success. First, aggravation of hyperglycemia as catabolic factor by intravenous nutrition may counteract any potential benefit of the artificial feeding. Second, preservation of muscle mass with forced nutrition may come at the expense of suppressed autophagy and compromised muscle quality and function.