Critical illness: an overview of the physiological and metabolic changes
The severely ill are a very heterogeneous group of patients but approximately half of all General Critical Care admissions suffer from severe sepsis. The presentation will therefore focus on the physiological and metabolic changes in this common critical care syndrome. Sepsis is initiated by microbiological invasion of host tissues and all severe cases are characterised by the rapid development of multiple organ failure. Outcome remains poor with in-hospital mortality in excess of 40%.
Host invasion by microbes triggers an intense inflammatory response. Key target tissues and circulatory cells (endothelial, epithelial, white cells) express surface receptors for microbes and their products. These initiate the inflammatory response which is then amplified by further pro-inflammatory cascades. The cause of multi-organ failure remains controversial but a number of circulatory and metabolic changes characterise severe sepsis. In the early stages tissue oxygen delivery is reduced, due to fluid loss across increasingly permeable vascular beds. Adequate volume resuscitation then leads to a characteristic high cardiac output state. Despite increased oxygen delivery to tissue beds there appears to be an impairment of oxygen consumption and cellular energetics.
Changes in both microvascular control and alterations in intracellular metabolism contribute to the problems of oxygen utilisation. Simultaneous dilation and constriction of the microvasculature occurs and may produce shunting, explaining the apparent fall in oxygen utilisation. An alternate, and not mutually exclusive, theory suggests that oxygen consumption is impaired by intracellular changes in metabolism. Mitochondria play a key role in cellular energetics, and their function may be impaired in sepsis.
The endocrine system has a central role in regulating the stress response and sepsis is associated with multiple changes in endocrine function. These changes, whether adaptive or mal-adaptive, are the subjects of much current research in the field of critical care.