Influence of critical illness on aspects of body composition and physiological function in the intensive care patient

Abstract

Critical illness is accompanied by a characteristic metabolic response, hallmarks of which include loss of protein, loss of skeletal muscle, and disturbed tissue hydration. In spite of both therapeutic gains, and a growing understanding of the fundamental processes that underlie this response, mortality rates remain high and the road to recovery is often prolonged and complicated. Non-structural protein molecules lie at the heart of many vital physiological functions, and it would seem reasonable to suggest that depletion of protein stores would lead to both physiological dysfunction and prolonged recovery. This thesis examines the impact of life-threatening illness on the modern day intensive care patient, looking specifically at extent of loss of body protein and skeletal muscle; it looks to determine the relative contribution of skeletal muscle to total protein losses. It seeks to determine whether erosion of skeletal muscle mass has an impact on physiological performance of skeletal muscle. Uncertainty exists as to the behaviour of cardiac muscle in catabolic illness states. This thesis answers the question of whether heart muscle acts as a protein store for consumption in such patients, and determines what happens to cardiac function in the critically unwell. It provides clinical evaluation of an exciting recent hypothesis1, which offers potential for modulating the loss of protein so often seen in the critically unwell patient. The thesis demonstrates that major multiple trauma, or life-threatening sepsis results in massive losses of both total body protein and skeletal muscle mass. At the same time, significant declines in both skeletal and respiratory muscle function ensue. The behaviour of cardiac muscle is quite different to skeletal muscle - both its composition and function remain intact in the setting of catabolic illness. The thesis shows that critically unwell patients undergo a change in cellular composition over time, with cells losing water in a progressively greater fashion relative to protein. This finding supports the hypothesis1 that protein loss in catabolic states is triggered and maintained by cell shrinkage and relative cellular dehydration.