Riley MS; Belfast City Hospital, Regional Respiratory Centre, Belfast, United Kingdom of Great Britain and Northern Ireland ; marshall.riley@belfasttrust.hscni.net.
Nicholls DP; Royal Victoria Hospital, Department of Medicine, Belfast, United Kingdom of Great Britain and Northern Ireland ; paul.nicholls@belfasttrust.hscni.net.
Cooper CB; Harbor-UCLA Medical Center , Div of Respiratory/Physiology & Medicine , 1000 W Carson Street , Torrance, California, United States , 90509 ; ccooper@mednet.ucla.edu.

Annals Of The American Thoracic Society [Ann Am Thorac Soc] 2017 Jun 07. Date of Electronic Publication: 2017 Jun 07.

Skeletal muscle requires a large increase in its adenosine triphosphate production to meet the energy needs of exercise. Normally, most of this increase in energy is supplied by the aerobic process of oxidative phosphorylation. The main defects in muscle metabolism that interfere with production of adenosine triphosphate are a) disorders of glycogenolysis and glycolysis, which prevent both carbohydrate entering the tricarboxylic acid cycle and the production of lactic acid, b) mitochondrial myopathies where the defect is usually within the electron transport chain, reducing the rate of oxidative phosphorylation and c) disorders of lipid metabolism. Gas exchange measurements derived from exhaled gas analysis during cardiopulmonary exercise testing can identify defects in muscle metabolism because oxygen consumption and carbon dioxide production are abnormal at the level of the muscle. Cardiopulmonary exercise testing may thus suggest a likely diagnosis and guide additional investigation. Defects in glycogenolysis and glycolysis are identified by a low peak oxygen uptake and absence of excess carbon dioxide production from buffering of lactic acid by bicarbonate. Defects in the electron transport chain also result in low peak oxygen uptake, but because there is an over-reliance on anaerobic processes, lactic acid accumulation and excess carbon dioxide from buffering occur early during exercise. Defects in lipid metabolism result in only minor abnormalities during cardiopulmonary exercise testing. In defects of glycogenolysis and glycolysis and in mitochondrial myopathies other features may include an exaggerated cardiovascular response to exercise, a low oxygen-pulse and excessive ammonia release.