Korean J Crit Care Med.  2010 Mar;25(1):9-15. 10.4266/kjccm.2010.25.1.9.

Mechanisms of Muscle Wasting in Patients with Sepsis

• Lee GD
• Kim HC

• KMID: 2301449
• DOI: http://doi.org/10.4266/kjccm.2010.25.1.9

Abstract

Muscle wasting is commonly seen in patients with sepsis as a consequence of the catabolic response in skeletal muscle. Muscle wasting can occur in cases that have an imbalance between degradation and synthesis of muscle proteins. Although decrements in the synthesis of muscle proteins may contribute to sepsis-induced muscle wasting, it has been recognized that increments in its degradation play a more essential role in muscle wasting. Muscle wasting in sepsis patients has some significant clinical consequences such as reduced ambulation and exercise tolerance, and an increased risk for pulmonary and thromboembolic complications. Several mechanisms have been proposed for sepsis-induced muscle wasting. Increased proteolysis via the ubiquitin-proteasome pathway and the calpains system is one of the principal mechanisms of muscle wasting induced by sepsis. Calpains are activated by calcium, which increases in patients with sepsis. The activation of the calpains system disrupts the sarcomere of the myofibrils, resulting in the release of myofilaments that are subsequently ubiquitinated and degraded by the 26S proteasome complex. Recent studies have suggested that transcriptional factors such as NF-kappaB and FoxO, and the apoptosis and autophagy-lysosome pathways may also be involved in sepsis-induced muscle wasting. This review briefly summarizes the contribution of these mechanisms of muscle wasting in patients with sepsis and the possible therapeutic agents to treat it.

Keyword

atrophy; muscle wasting; sepsis; skeletal muscle

MeSH Terms

Apoptosis
Atrophy
Calcium
Calpain
Exercise Tolerance
Humans
Muscle Proteins
Muscle, Skeletal
Muscles
Myofibrils
NF-kappa B
Proteasome Endopeptidase Complex
Proteolysis
Sarcomeres
Sepsis
Ubiquitin
Walking
Calcium
Calpain
Muscle Proteins
NF-kappa B
Proteasome Endopeptidase Complex
Ubiquitin