774 SUBLETHAL INTOXICATIONS 



selves as necrotic or inflammatory changes in the organ affected; (4) specific effects, 

 due to the special affinity possessed by the toxic products of certain bacteria for 

 certain organs or tissues in which they accumulate in greater concentration and where 

 they produce effects that are more or less constantly characteristic and specific. 



LOCAL EFFECTS 



The local effects of bacterial toxic products vary with the type of poison and with 

 its concentration and dosage. Diphtheria toxin causes a local necrosis accompanied 

 by a marked inflammatory reaction with an exudate rich in fibrin. This is equally 

 true whether the intoxication occurs spontaneously or is induced experimentally. In 

 ordinary infections of the throat with the diphtheria bacillus, the surface epithelium 

 becomes necrotic and an exudate of fibrin and leukocytes becomes entangled in this 

 necrotic material. This "membrane" is, by the mechanism of its formation, adherent 

 to the underlying tissues, and bleeding occurs when attempts are made to remove it. 

 When diphtheria toxin in sublethal doses is injected subcutaneously, a local necrosis 

 and exudate results which may slough out leaving an ulcer. In immunizing against 

 diphtheria with toxin-antitoxin there frequently occurs a local inflammatory reaction 

 which, however, rarely goes so far as to induce necrosis. 



The toxins of B. tetani and B. botulinus produce relatively slight local effects. Their 

 action is more definitely specific. The toxin of B. ivclchii appears to be a true soluble toxin, 

 but differs in certain material respects from those just mentioned. It is actively hemolj^tic 

 both in vitro and in vivo. When injected subcutaneously or intramuscularly it causes a local 

 edema and necrosis with a marked inflammatory reaction in the surrounding tissues.^ 



The local effects of true soluble bacterial toxins are not therefore strictly specific, that 

 is, they do not produce lesions whereby the type of toxin can be readily identified by the 

 type of changes produced in the tissues. The fixed bacterial toxins, the endotoxins, induce 

 changes which differ in certain respects from those which result from the action of the 

 true or soluble toxins. In general, the exudate induced by the injection of endotoxins is 

 less rich in fibrin, and the necrosis is also somewhat different in type. 



The endotoxins of most bacteria have a positive chemotactic effect and induce the forma- 

 tion of an abscess when injected subcutaneously or intramuscularly. Much the same effects 

 are produced when a suspension of living or of killed staphylococci is injected beneath the 

 skin. The bodies of the dead micro-organisms contain the chemotactic substance. The 

 changes which occur in the surrounding tissues are essentially those of an acute inflammation. 

 The products liberated by the disintegration of the staphylococci (i) attract leukocytes in 

 great numbers into the area of their activity; (2) cause necrosis of that portion of the fixed 

 tissues with which they come in contact in greatest concentration; and (3) kill many of the 

 leukocytes which have been attracted into the region. These three bacterial products of the 

 staphylococcus, namely, the chemotactic, the necrotizing, and the leukocytocidal, are, by 

 their interaction, responsible for the formation of the peculiar type of concentric inflamma- 

 tion, the abscess, which is the characteristic lesion produced by the staphylococcus in tissues 

 in any part of the body. The leukocj^tes killed by the leukocidin of the staphylococcus 

 liberate, upon their disintegration, their very powerful proteolytic ferments which digest and 

 liquefy the necrotic tissues, thus forming a cavity filled with pus.^ 



' Bull, C. G., and Pritchett, I. W.: J. Exper. Med., 26, 119, 367, and 603. 1917. 

 ^ Jochmann, G.: Virchow's Arch. f. path. Anal., 194, 342. 1908; Opie, E. L. : Arch. Int. Med., 

 5, 541- 1910- 



