Pathogenesis 75 



PATHOGENESIS 



This subject can be understood only through a broad knowledge 

 of the metabolic products of micro-organisms. In general it may 

 be said that the ability of micro-organisms to do harm depends upon 

 the injurious nature of their products. This alone, however, will 

 not explain the phenomena of infection, for in many cases the in- 

 toxication is subsidiary in importance to the invasive power of the 

 micro-organisms. Some bacteria having but limited toxic powers 

 possess extraordinary powers of invasion, as Bacillus anthracis, 

 and the intoxication becomes important only after the organisms 

 have penetrated to all the tissues of the body. Others, with more 

 active toxic properties, have but limited invasive powers, and a few 

 organisms, growing with difficulty in some insignificant focus, ex- 

 cite actively destructive reactions in the tissues with which they 

 come in contact. Still others, with limited invasive powers, 

 eliminate active toxic substances, soluble in nature, that enter the 

 circulation and act upon cells remote from the bacteria themselves, 

 as in diphtheria and tetanus. 



The invasive power of the organisms depends upon their ability 

 to overcome the body defenses. This may indicate activity of the 

 infecting organism, or weakness of the defensive mechanism. The 

 relation of these factors is exceedingly complex, only partly under- 

 stood, and will be fully discussed in the chapter upon Immunity. 



For convenience toxins may be described as intracellular or in- 

 soluble, and extracellular or soluble. 



The intracelltilar toxins. Until the investigations of Vaughan, 

 Cooley and Gelston,* and later Vaughan and his associates, Det- 

 weiler,t Wheeler,^ Leach,§ Marshall and Gelston,|| Gelston,** J. 

 V. Vaughan,tt Wheeler,tt Leach,§§ Mclntyre,|||l and others, it 

 seemed remarkable that micro-organisms whose filtered cultures 

 contained little demonstrable toxic substance are sometimes able 

 to produce active pathogenic effects. By means of special apparatus 

 in which the micro-organisms could be cultivated in enormous quan- 

 tities, and the disintegration of the micro-organismal masses secured 

 by subjecting them to high temperatures, to the action of mineral 

 acids or autolysis, it was discovered that the colon bacilli, typhoid 

 baciUi, and many supposedly harmless bacteria contain intensely 

 active toxic substances. In all probability some of the toxic sub- 

 stances produced by such means are artefacts, but enough work 

 has been done to prove that insoluble toxic substances are present 

 in such organisms, and the toxic substances obtained by the com- 



* "Journal of the American Medical Association," Feb. 23, 1901; "Trans. 

 Assoc. Amer. Phys.," 1901; "American Medicine," May, 1901. 

 t "Trans Asso. Amer. Phys.," 1902. t Ibid. 



§ Ibid. II Ibid. **Ibid. 



ft Ibid. 



it "Jour. Amer. Med. Assoc," 1904, xlii, p. 1000. 

 §§ Ibid., p. 1003. III! Ibid., p. 1073. 



