Intracellular composition and homeostatic mechanisms in severe chronic infantile malnutrition. IV. Development and repair of the biochemical lesion.

The water and electrolyte compositions of serial biopsies of skin and muscle obtained from children with severe chronic malnutrition have been related to balance data, obtained simultaneously in some of them, and to renal adjustments during hypotonic dehydration. The composition of diarrheal stools and specimens of urine obtained daily are given. While the number of observations is limited, severe chronic malnutrition with imbalance of electrolytes or water would seem to be characterized by the following features: Extracellular hypotonicity with expansion of the aqueous intracellular phase in muscle of non-atrophic children irrespective of reduction or expansion in volume of the extracellular phase. Increase in the ratio of intracellular to extracellular content of water often is accompanied by accumulation of sodium within the cell, quite independent of content or concentration of potassium in the cell. Either the osmotic properties of the cell or cell metabolism, or both, are altered. This progression is accelerated by intercurrent events of acute nature and is reversed during recovery. Death resulting from dehydration (or infection) superimposed upon severe malnutrition may be associated with sudden further expansion of the intracellular phase at the expense of the extracellular fluids. Content of sodium in the cell increases markedly. Balance data obtained in one such patient could not be reconciled with change in composition of the tissue. Slow renal and tissue response to malnutrition leads to marked reduction in total mass of tissue, but reconstitution of surviving tissue, presumably by utilization of substances released by catabolism of cells. The etiology of the characteristic hypotonicity of the body fluids is not known. Hypotonicity probably results from release of endogenous water from catabolism of cells, depletion of protein, recurrent loss of water and solute in diarrheal stools, and an intake of water relatively in excess of solute. Overhydration of the intracellular phase is a consequence of the extracellular hypotonicity. Excretion of a relatively hypotonic urine is interpreted as a defense of concentration of solutes in the body water, and reduction in the volume of glomerular filtrate might be interpreted as a limiting defense for sustaining the volume of body water. Redistribution of body water with very prompt contraction of the overhydrated intracellular phase and expansion of the extracellular phase of the body may be achieved by infusion of hypertonic solutions to severely dehydrated, malnourished, hypotonic infants. However, further careful examination of this phenomenon is needed to define the limitations of infusion and response before extensive use of hypertonic solutions in therapy of even the extreme cases can be advocated with safety. An hypothesis is hazarded concerning the development of the biochemical lesions of the cells and tissues in chronic malnutrition. It is suggested that despite apparently different clinical features, chronic malnutrition with respect to proteins and calories in infants may be interpreted as a continuous process of disturbance at a cytoplasmic level which gradually narrows the flexibility of renal and cellular responses. Superimposed acute catabolic events like diarrhea or infection eventually overcome the limits of renal and of cellular compensation, thus leading to irreversible intracellular biochemical derangement and death.