240 DEFENSE AGAINST NON-ANTIGENIC POISONS 



means by which this fixation is brought about are unknown. It is possible that the 

 power of the tissues to bind poisons may become increased bj' repeated doses, lead- 

 ing to "specific acquired tolerance. '"^^ According to Slowtzoff^' arsenic is fixed 

 by the nucleus in a very firm combination;'* mercury by globulins in a less stable 

 combination; copper by the nucleins, but less firmly than the arsenic. Other 

 poisons, chiefly alkaloids, are probably combined with bile acids. Possibly some 

 poisons combine with glycogen. These compounds are but slowly broken up, and 

 thus the poison reaches the more susceptible and more important tissues in a rela- 

 tively diluted condition. The bones seem to hold in harmless form poisonous 

 fluorides, and to less extent arsenic, barium, and tungsten, which persist in the 

 bones for a great length of time. Leucocytes are possibly important binders of 

 poisons, perhaps through combination with their nucleins,'^ but storage in these 

 labile cells is necessarily of relatively brief duration. 



3. Combination with substances formed or contained in the tissues; the result- 

 ing substance being less toxic than the poison alone. Under this heading may be 

 included both chemical combination and physical absorption or solution, such as 

 the deviation of the lipoid-soluble narcotics from the central nervous system by 

 excessive tissue fats, or by fats therapeutically introduced.'* Many poisons 

 combine with the inorganic constituents of the tissues; e. g., btyium and various 

 aromatic substances with SO4; silver with CI, etc. 



4. Chemical alteration, with or without subsequent combination with other sub- 

 stances, by such means as oxidation, reduction, hydrolysis, and neutralization. 



5. Impaired absorption should also be considered as a means of defense against 

 poisons. This may depend upon the injury to the gastro-intestinal tract produced 

 either by the poison itself or by some independent pathological condition. Cloetta 

 considers impaired absorption important in acquired immunity to arsenic (see 

 below) and it may also modify the effects of other poisons." 



The chemical reactions employed in defense against simple chemical 

 poisons have been particularly considered bj^ E. Fromm,^^ whose out- 

 line is here partially followed, and to which the reader is referred for 

 bibliography. 



INORGANIC POISONS 



MetaUic poisons, such as lead, silver, mercury, and arsenic, are 

 made insoluble, particularly by forming compounds with proteins in 

 the alimentary tract, intestinal walls, blood, or internal organs; also 

 by forming sulphides with the H2S of the intestinal contents. Accord- 

 ing to Cloetta^^ immunization against arsenic depends entirely upon 

 a reduction of absorption in the intestine, for the longer arsenic is 

 taken, the less appears in the urine and the more appears in the feces. ^^ 

 At the same time the resistance to arsenic injected subcutaneouslj^ 

 is not increased at all, and no increase in resistance can be obtained 



'2 Santesson, Skand. Arch. Physiol., 1911 (25), 28. 



'■' Hofmeister's Beitr., 1901 (1), 281; 1902 (2), 307. 



" Denied by Heff'ter. (Arch, intcrnat. de Pharmacodyn., 1905 (15), 399), who 

 considers it more a i)hysico-clK'mical process. 



'* Stessano, Comjjt. Rend. Acad. Sci., 1900 (131), 72. 



'«See (Iraham, Jour. Inf. Dis., 1911 (8), 147. 



"v. Lhota, .Vrch. internal, pharmacodyn., 1912 (22), (il. 



'* "Die cheniischen Schiitzmittel des Tierkorpers bei Vergiftungen," Strassburg, 

 Karl Triibner, 1903. See also r6sum6 by EUinger, Deut. med. Woch., 1900 (26), 

 580. 



'* Arch. exp. Path. u. Pharm., 1906 (54), 196; Corresponbl. Schweizer .\oTzte, 

 1911 (41). 737. 



^" Not accepted bv lluusmann, Krgel)nisse Physiol., 1907 (6), 58; or Joachi- 

 nioulu, .Vrch. cxi). Path.. 1916 (79). 119. 



