THE FORMATION OF UREA 663 



tained indirectly from proteid. But urea has been obtained 

 directly from proteid in two ways, either by oxidation in the 

 presence of ammonia or by prolonged heating with baryta. 



We shall first consider the various views which have been 

 held as to the nature of the immediate precursors of urea in the 

 body, and the process by which their conversion into urea is 

 carried out, and then deal with the seat of urea formation. 

 Unfortunately much of the work on this subject is now known 

 to be unreliable because of the methods used in the detection 

 and estimation of urea. The methods of Bunsen and Schondorff 

 were extensively used ; they are now only of historical interest, 

 and need not be further discussed than to say that there is no 

 guarantee that the substance being estimated is wholly urea. 

 Salkowski's modification of Bunsen's method is more satisfac- 

 tory. For in it the ammonia as well as the C0 2 split off from 

 the separated substance are estimated, and if these two bear 

 a certain proportion to each other, the substance from which 

 they are derived is presumably urea. Even the more modern 

 method of Morner and Sjoquist is not free from serious fallacy. 

 The principle of the method is that a mixture of alcohol and 

 ether after the addition of a solution of barium chloride and 

 barium hydrate precipitates all nitrogenous constituents except 

 urea and ammonia. The urea-nitrogen is determined in the 

 concentrated filtrate, after driving of! the ammonia, by Kjeldahl's 

 method. It is now known that hippuric acid, kreatinine and 

 traces of allantoin are estimated with the urea, and there is the 

 further possibility that the nitrogen of other less well-known 

 substances may be simultaneously estimated. A more reliable 

 method is that of Folin. This is based on the fact^ that when 

 urine is heated with hydrochloric acid and crystalline magnesium 

 chloride the nitrogen of urea, but not of other substances, is 

 decomposed into ammonia. The ammonia produced is distilled 

 off and determined by titration. The preformed ammonia in 

 the urine is separately estimated and the urea-nitrogen calculated 

 by difference. Even more trustworthy is a combination of the 

 methods of Morner and Folin. The preliminary precipitation is 

 carried out by Morner and Sjoquist's method, and the concentrated 

 filtrate so obtained is then treated by Folin's method. The most 

 certain method of detecting urea is to separate crystals of it, or 

 of one of its compounds, and determine their melting-points, or 



