METABOLISM IN NEPHRITIS 319 



teins is not at all clear. The investigations upon the subject of the serum 

 proteins are replete with suggestions and possibilities but have thus far 

 furnished very little else of importance. 



The Non-Protein Nitrogen of the Blood and Tissues 



in Nephritis 



The total non-protein nitrogen is made up of the sum of various sub- 

 stances derived from the digestion or disintegration of protein. The urea, 

 uric acid, creatin, creatinin, amino acids, go to make up the major if 

 not the entire amount of non-protein nitrogen. A certain fraction some- 

 times remains unaccounted for ; this has been variously called the residue, 

 rest or undetermined nitrogen. The author once asked a prominent bio- 

 chemist as to what he thought this residue nitrogen was composed of. The 

 response was very simple and direct : "The rest nitrogen represents the 

 sum of the inaccuracies of the methods for the determination of the in- 

 dividual non-protein nitrogenous constituents; there is no undetermined 

 nitrogen." This is a sweeping statement but it has more to be said for 

 it than against it. In the first place, any one who has carried out many 

 fairly complete analyses of the blood has encountered specimens in which 

 the sum of the nitrogen derived from the non-protein nitrogenous con- 

 stituents was greater than the total non-protein nitrogen value. In the sec- 

 ond place, an accurate determination of the total non-protein nitrogen is 

 impossible of attainment at the present time. This is not so much the 

 fault of the methods as it is that it is not known at what point in the 

 cleavage of protein into polypeptids, protein ceases to be protein and the 

 non-protein nitrogen begins. The results obtained by chemical methods in 

 vogue are consequently very different ; in the preliminary step in these 

 estimations, various coagulants are vised to separate the protein from the 

 non-protein fraction in the blood or tissue. If trichloracetic acid is em- 

 ployed, according to the method of Greenwald, the figures for non-protein 

 nitrogen are considerably higher than when Folin's procedure, which re- 

 sorts to methyl alcohol, is followed. Thus the figures for total non-protein 

 nitrogen have comparative value only; the substances which the term 

 represents are not definitely decided upon. The undetermined nitrogen 

 for the present at least is a mythical substance and it does not seem wise 

 to attribute any significance to it until it is more definitely established 

 that it really exists. Inasmuch as the total non-protein nitrogen is made 

 up of various nitrogenous constituents, it remains to determine the rela- 

 tion of these to one another in the blood and tissues as affected by nephritis. 



As renal insufficiency develops, the uric acid is first retained in the 

 blood, then the urea and, finally, the creatinin (see comparative value 

 of uric acid, urea and creatinin in nephritis). The creatin may increase 



