Sepsis--the Wayne State University Symposium--part III. Bacteremia and endotoxemia: a discussion of their roles in the pathophysiology of gram-negative sepsis.
Bacteremia, or the presence of live bacteria in the bloodstream, does not seem a prerequisite for septic shock. Indeed, only a small portion of all patients who sustain gram-negative bacteremia ever develop the shock syndrome. Endotoxin in the laboratory model is capable of producing a number of pathophysiological alterations which can partly explain the varied picture of septic shock seen in man. Endotoxin is released from gram-negative bacteria upon their death, and it probably acts as an antigen which reacts with antibody and subsequently activates the complement cascade. The resultant production of vasoactive polypeptides and release of histamine from mast cells might account for the increased vascular permeability and early hyperdynamic cardiovascular function seen in septic shock. These changes may also contribute to ultimate stagnation and pooling in the peripheral microcirculation. Endotoxin is a potent stimulus to the sympathoadrenal system which causes varying effects on the periphery. Continued catecholamine stimulation at the periphery may ultimately contribute to stagnant anoxia by an effect on pre- and postcapillary sphincters. Endotoxin, by itself, will not directly impair cardiac contractility, but evidence for depressed function implies an interaction of endotoxin with other biochemical systems, such as vasoactive polypeptides, to indirectly produce the observed effects. Expression of a hemodynamic model closely approximating human septic shock requires, in addition to a source of endotoxin, a focus of inflammation. Such a focus, in all probability, supplies some as yet unidentified factor(s) which help produce the observed increase in cardiac output. The Limulus test has confirmed the presence of endotoxemia in gram-negative shock and has raised questions about the contribution of gut flora to the propagation of the syndrome. An enterogenous source of endotoxin may also be important in patients in whom a source of inflammation is not readily observable. Gram-negative shock remains an important and grave clinical problem. Knowledge about the relative roles of endotoxin various foci of inflammation, and generation of vasoactive peptides is accumulating slowly. Hopefully, by creating a clearer understanding of the pathophysiology, such knowledge will ultimately result in further improvement in our efforts to prevent and treat this syndrome.