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The data here reported (Table I) show that a toxin is present in the blood of animals with two types of irreversible hypovolemic shock. These data also show that although blood volume therapy does not correct the hypovolemia because of continuing loss of plasma at the site of injury, the major factor in the progressive decline and death is the endotoxemia rather than the hypovolemia. This is also true of severe and prolonged hemorrhagic shock that is irreversible to transfusion. The data also show that even when there is bacterial activity at the site of injury, the pool of endotoxin in the intestine is the chief source of the circulating endotoxin. In all three types of shock, the endotoxemia develops because persisting hypovolemic shock renders the RE system unable to destroy the endotoxin. The demonstration of an endotoxemia as the cause of irreversibility and death in three types of traumatic shock caused by three different agents suggests that a single pathophysiological mechanism accounts for the phenomenon of irreversibility in all types of traumatic shock.

After intravenous injection in mice, rabbit immune complexes, solubilized in antigen excess and containing fluorescent antigens (BSA* or OA*) or fluorescent antibody, or both, were promptly localized in reticuloendothelial cells, and polymorphonuclear leukocytes, of the sinusoids of liver and the red pulp of spleen; in glomeruli and elsewhere in kidney; in capillary endothelium of heart and lung; and in hepatic cells. Thereafter manifold processes occurred. Within 48 hours the immune complexes were scarcely detectable in liver and splenic red pulp but now were localized in the germinal centers of white pulp where heretofore they had been seen only in trace amounts. This new localization presumably was associated with the antibody-forming activity of the germinal centers, for the immune phase of antigen clearance from the blood had already begun. Although the immune complexes were localized in various regions of the nephrons and their appertaining blood vessels, the initial sites of predilection were the glomerular capillary walls and intercapillary spaces. After 48 hours the immune complexes were still detectable, although in diminished amounts, in the glomeruli but had by now essentially disappeared from other renal sites. The localization of immune complexes in the kidney was associated with proteinuria and with structural changes which closely simulated in some instances those of human membranous glomerulonephritis, of focal and diffuse types, and consisted mainly of eosinophilic swellings of the glomerular capillary walls, intercapillary spaces, and basement membranes. There was a close correspondence between the distributions of the eosinophilic swellings and the fluorescent immune complexes. The renal localization and persistence of fluorescent antigens (BSA* or OA*), after separate injections in mice, differed from that of fluorescent immune complexes in several respects. For example BSA* showed predilection for the glomerular basement membranes and was localized sparsely in the capillary walls and intercapillary spaces; OA* was localized only in minute amounts; and neither was detectable in more than trace amounts at 48 hours after injection. These fluorescent proteins (of low molecular weights, 40,000, 70,000) did not cause glomerulonephritis within the time interval studied, whereas fluorescent immune complexes, containing on the average two molecules of antigen to one of antibody (with minimum molecular weights of 240,000 to 300,000) produced glomerulonephritis in some instances, in confirmation of the observations of others. Since the localization of the immune complexes occurred immediately and without known immunologic relation to the kidney itself, the selective physical retention of proteins by structures comprising the glomerular ultrafilters appeared to be of pathogenic significance in this form of membranous glomerulonephritis in mice, as perhaps also in nephrotic glomerulonephritis in man. If after injection of fluorescent immune complex, homologous antiserum was also administered intravenously so as to produce acute anaphylactic death, coarse and occlusive depositions of immune precipitates occurred in pulmonary, myocardial, and renal capillaries, and in hepatic sinusoids.