Significance of Carbohydrate Metabolism and Local Acidosis in Inflammation. ∗

Earlier studies by one of the writers have indicated that the cytological sequence in inflammation, characterized by primary infiltration of polymorphonuclear leucocytes followed by mononuclear phagocytes, seems to be conditioned by the local hydrogenion concentration of the exudate. 1 With the developing local acidosis in an area of inflammation polymorphonuclear cells degenerate and are replaced by macrophages. If the pH is maintained above 7.0 the polymorphonuclear cells predominate. The cytological picture can be fairly well predicted from the pH of the exudate and vice-versa. In many cases the pH changes appear to precede the cytological shift which, however, invariably follows. Further studies show that the mechanism of local acidosis in inflammation is referable to a disturbance of local carbohydrate metabolism. With impairment in the local circulation, as indicated by lymphatic blockade and thrombosis of small vessels, it is conceivable that a state of relative anoxemia develops. 2 Anaerobic glycolysis follows. Lactic acid is found to increase two to fourfold as the inflammation progresses. The sugar in the exudate correspondingly falls sharply, revealing a conversion into lactic acid. Most of the inflammatory exudates studied were induced by the injection of small amounts of turpentine, administered sometimes in divided doses, into the pleural cavity of dogs. With the progress of the inflammatory reaction the local alkali reserve soon becomes depleted, as determined by the volume percent of CO₂ content. An uncompensated acidosis follows; the volume percent of CO₂ falling in some instances from 40 to 29 and even to lower levels. The pH falls and the polymorphonuclear cells are replaced by macrophages. Below a pH of 6.8 or 6.7 most types of leucocytes are damaged and frank pus results. The observations indicate that the cytological picture in inflammation seems to be conditioned by the pH, which in turn is referable to the increased rate of glycolysis and the local depletion of the alkali reserve. These studies have obvious implications in regard to the factors determining various histological manifestations of inflammatory lesions. Their bearing on the mechanism of suppuration is likewise evident and is being studied in the case of lesions induced by various pyogenic and non-pyogenic organisms. The present conclusions are based on results obtained with 7 dogs. For the purpose of illustration a type experiment is presented in Table I. The details of this investigation will form the subject of a separate communication.