FORMATION OF THE URINARY CONSTITUENTS. 425 



collected the dilute urine from the Malpighian corpuscles before it passed through Henle's 

 loops. ] 



274. FORMATION OF THE URINARY CONSTITUENTS. The question 

 has often been discussed, whether all the urinary constituents are merely excreted 

 through the kidneys, i.e., that they exist preformed in the blood; or whether some 

 of them do not exist preformed in the blood, but are formed within the kidneys, as 

 a result of the activity of the renal epithelium. 



Urea is formed Outside the Kidney. Urea exists preformed in the blood, from 

 which it is separated by the activity of the kidney. This is proved by the follow- 

 ing considerations : 



1. The blood contains one part of urea in 3000 to 5000 parts, but the renal vein contains less 

 urea than the blood of the corresponding artery. 



2. After extirpation of the kidneys, or nephrotomy, or after ligature of the renal vessels, the 

 amount of urea accumulates in the blood, and increases with the duration of the experiment to 

 T5T to ? ^. At the same time there is vomiting and diarrhoea, and the fluids so voided con- 

 tain urea ( CI. Bernard). Animals die in from one to three days after the operation. 



3. After ligature of the ureters, the secretion of urine is soon arrested. Urea accumulates 

 in the blood, but not to a greater extent than after nephrotomy. It is possible, however, that 

 the kidneys, like other organs, may form a small amount of urea, due to the metabolism of their 

 own tissues. 



[Urea exists in the blood, whence does the blood derive it ? It can only obtain 

 it from one or more of several organs (1) muscle, (2) nervous system, and (3) 

 glands, of which the liver is the most prominent. This is best stated by the method 

 of exclusion.] 



[1. That urea is not formed in muscle is shown, among other considerations, by the fact that 

 only a trace of urea occurs in muscle ( 293), and that the amount is not increased by exercise. 

 Blood which has been transfused through a muscle, or the blood after circulating in a muscle 

 during violent exercise, does not contain an increase of urea, nor does the addition of ammonia 

 carbonate to blood circulating through muscle show any increase of urea. Again, muscular 

 exertion does not (as a rule) increase the amount of urea in the urine, as shown by the experi- 

 ments of Fick and Wislicenus ( 294), Parkes, and others. The excretion chiefly increased by 

 muscular exertion is the pulmonary C0 2 ( 127).] 



[2. From what we know of the nervous system, it is not formed there. We are therefore 

 forced to consider the evidence as to the liver, as the organ, or, at least, the chief organ in which 

 it is formed. This evidence is in some respects contradictory, but it is partly experimental 

 and partly clinical. Although Hoppe-Seyler denies the existence of urea in the liver, its 

 existence there was proved by Gscheidlen ; and Cyon, on passing blood through an excised liver 

 by the "perfusion" method of Ludwig, found that blood, after being passed several times 

 through the organ, contained an increased amount of urea. The objection to these experiments 

 is that Cyon's method of estimating the urea was unreliable. But von Schroeder, using a simi- 

 lar method, finds that if blood be perfused through the liver of a dog in full digestion, there is 

 a great increase in the amount of urea, while there is none in the liver of a fasting dog. If 

 ammonia carbonate be added to the blood, there is a very much greater amount of urea in the 

 blood of the hepatic vein. This last fact is confirmed by Salomon. The experiments of 

 Minkowski on the liver of the goose ( 386) show that, when the liver is excluded from the 

 circulation, lactic acid takes the place of uric acid in this bird. Brouardel further states, 

 that if the region of the liver be so beaten as to cause congestion of that organ, there is an 

 increase of the urea in the urine.] 



[The clinical evidence points strongly to the formation of urea in the liver. Parkes pointed 

 out that in hepatic abscess, during the early congestive stage, the urea in the urine is increased, 

 while it is diminished in the suppurative stage, when the hepatic parenchyma is destroyed. The 

 urea is also diminished in cancer of the liver, phthisis, and some forms of hepatic cirrhosis, 

 while it is increased during hepatic congestion, and specially so in some cases of diabetes melli- 

 tus. The most striking fact of all is that, in acute yellow atrophy of the liver, the urea is 

 enormously diminished in the urine, and may even disappear from it while its place is taken by 

 the intermediate products, leucin and tyrosin (v. Frerichs). In poisoning by phosphorus, coin- 

 cident with the atrophy of the liver, there is a fall in the urea excretion. Noel-Paton finds 

 that some drugs which increase the quantity of bile in dogs in a state of N-equilibrium ( 178), 

 e.g., sodic salicylate and benzoate, colchicum, mercuric chloride and euonymin also increase the 

 urea in the urine, he therefore concludes "that the formation of urea in the liver bears a very 

 direct relationship to the secretion of bile by that organ."] 



As to the antecedents of urea there is the greatest doubt ( 256). 



