NEUTRALITY OF THE TISSUES AND TISSUE-FLUIDS 275 



Another method which has been extensively employed in the investi- 

 gation of the reactions of blood-serum and of other tissue-fluids is the 

 Indicator-method of Friedenthal which has been especially applied to 

 these investigations by Sorensen. This method consists in adding 

 to the fluid under investigation a number of different indicators known 

 to display color-changes, at differing hydrogen or hydroxyl ion concen- 

 trations. The same indicators are also added to a series of mixtures 

 of monosodium and disodium phosphate, of which the former is acid 

 in reaction and the latter alkaline. The hydrogen ion concentration of 

 all possible mixtures of these salts has been determined, and that 

 mixture which yields most nearly the same tints with indicators as the 

 unknown fluid evidently corresponds to it in hydrogen ion concentra- 

 tion. This method is not applicable to a highly colored fluid such as 

 whole blood since the tints of indicators are not accurately appreciable 

 in such a fluid. Furthermore it is to be noted that the indicators most 

 suitable for this purpose are precisely those which are least desirable 

 for the ordinary purposes of direct titration, because the best indicator 

 for titration is that which displays a sharp change from one tint to 

 another at a certain reaction, whereas the best indicator for the indirect 

 method of titration just described is evidently one which offers a large 

 number of appreciable changes of shade or tint within a limited range 

 of hydrogen ion concentrations. The most suitable indicator for the 

 purposes of indirect titration within the range of reactions commonly 

 met with in tissue-fluids, is Phenol Sulphonphthalein. Finally it should 

 be carefully noted that the choice of indicators is limited to those which 

 do not react chemically with the proteins or other substances commonly 

 present in tissue-fluids. A variety of dyes which "are commonly 

 employed as indicators in direct titration are unsuitable for our purpose 

 because they interact with proteins and the compounds which are 

 formed do not change color at the hydrogen ion concentration at which 

 the free dye changes color, or even may display totally different colors 

 from those which the free dye exhibits. 



By these various methods it has been ascertained that not only is the 

 blood of all vertebrates very nearly neutral in reaction, but almost all 

 of the tissue-fluids are also approximately neutral. Thus the Pan- 

 creatic Juice, the most alkaline of body-fluids, contains 5 x 10~ 9 H+, 

 corresponding to an alkalinity of 13 x 10~ 7 OH~ or a little over one 

 millionth normal. Hitherto, according to Friedenthal, no animal 

 fluid has been found which contains less than 10~ 10 H + , that is, more 

 than about 10Q 6 000 normal OH~. 



Now the neutrality of the blood is maintained with extraordinary 

 exactitude despite the fact that a large proportion of the products of 

 metabolism are acid in reaction and are washed out of the tissues in 

 which they are formed, into the blood. The products of muscular 

 activity include carbon dioxide, lactic acid and acid phosphates, and 

 the muscular exertion which is involved, for example, in climbing a 

 steep hill involves the expenditure of a very considerable number of 



