Changes in body balances of nitrogen and other key nutrients: description and underlying mechanisms

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Abstract
This paper represents an attempt to explain the apparent differences in host metabolism between prolonged fasting or starvation and the anorectic state which accompanies severe infection. The differences are discussed in terms of a purposeful redistribution of amino acids from peripheral to visceral tissues for various aspects of host defense, in particular for the synthesis of acute phase globulins. Phagocytosis is the proposed trigger for this redistribution of amino acids and increased acute phase globulin synthesis, as well as for an array of physiological alterations which include, but are not necessarily limited to, fever, decreased plasma zinc and iron, increased plasma copper (ceruloplasmin), glucagon, and insulin. A concomitant (and perhaps consequence) of phagocytosis is the release of factors such as pyrogen and leukocytic endogenous mediator. These mediators are capable of initiating a wide range of metabolic alterations associated with infection. The panoply of metabolic alterations which occur after phagocytosis and before the development of immunity is presented as a necessary part of an integrated host response to inflammatory stress. The redistribution of trace metals and the increased acute phase globulin synthesis appear to provide both positive and negative feedback: 1) by delimiting tissue damage occasioned by the infection or by phagocytes in response to infection; 2) through increase of phagocytic capacity, in part by promoting granulopoiesis; and 3) by aiding in the inactivation of the microorganism and in the development of immunity. Consonant with the suggested import of the amino acid redistribution and increased acute phase globulin synthesis is the fact that, contrary to what is the case in the fasting state, plasma insulin is increased and ketosis is inhibited in severely septic animals and patients; both of these differences would contribute to continued catabolism of muscle. The fundamental value to host defense of these systemic metabolic alterations, in particular the increased acute phase globulin synthesis, is further indicated by the fact that they occur in a wide range of inflammatory illnesses and even under circumstances, such as malnourishment, which often lead to reductions in other host defense mechanisms, phagocytosis and cell-mediated immunity.