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patients in an effort to shorten convalescent recovery and decrease the length of hospital stay (Wilmore, 1991).

This chapter outlines some of the changes that occur in whole body protein metabolism following infection and injury. Evidence will be presented that these catabolic states result in marked translocation of protein from the carcass to visceral tissues, resulting in a net loss of skeletal muscle mass. Such loss results in decreased strength and activity.


Over 200 years ago, John Hunter, the British surgeon and biologist, recognized that accidental injury initiated a series of responses in the host that presumably aided tissue repair and general recovery (Hunter, 1794). In the late 1800s, the concept of nitrogen balance was established by Voit and his German colleagues working in this area of physiological biochemistry (Munro, 1964). They noted that nitrogen balance could be related to the body's protein economy and was affected positively by the increased ingestion of both energy and protein and affected negatively by sepsis-induced fever. These concepts were confirmed and extended in the early 1900s, when Coleman and DuBels (1915) studied both energy and protein balance in a group of patients with typhoid fever. Using both direct calorimetric techniques and whole body balance methodology, they studied patients during the acute and convalescent phases of their illness. The investigators described the increased net loss of nitrogen that was associated with the febrile episodes of typhoid fever; the negative nitrogen balance could not be offset by the ingestion of large quantities of energy at the moderate level of protein intake that was utilized.

In 1932, Cuthbertson (1932) described a group of patients who had either undergone orthopedic surgical procedures on their lower extremities or who had sustained long bone fractures. He noted that these injuries to the long bone were associated with an enhanced loss of nitrogen from the body. This negative nitrogen balance was maximal during the first week postinjury and persisted for up to I month. Cuthbertson divided the metabolic response to injury into two phases: an early, acute "ebb" or shock phase and a latter "flow" or hyperdynamic phase. During the ebb phase, there was decreased metabolic activity, which was followed within 12 to 48 hours by the flow phase, a hypermetabolic state in which metabolic rate, temperature, and urinary nitrogen excretion all increased. Others have since contributed to the field of postinjury metabolism, with classic contributions being made by John Howard, Oliver Cope, Francis Moore, John Kinney, and many others (Wilmore, 1997).

During the early 1900s, researchers realized that infection was related to increased loss of protein from the body, but it was not until the 1960s that the systematic study of the metabolic response to infection was undertaken and published. William Beisel and colleagues (1967), working with the Army to

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