>6 THE URINE [CH. XXXVII. 



rapidly discharged by the expired air. Eecent careful research has, 

 however, shown that an increase of nitrogenous waste does occur on 

 muscular exertion, but appears as urea in the urine to only a slight 

 extent on the day of the work ; the major part is excreted during the 

 next day. 



Where is Urea formed ? The older authors considered that it 

 was formed in the kidneys, just as they also erroneously thought that 

 carbonic acid was formed in the lungs. Prevost and Dumas were 

 the first to show that after complete extirpation of the kidneys the 

 formation of urea goes on, and that it accumulates in the blood and 

 tissues. Similarly, in those cases of disease in which the kidneys cease 

 work, urea is still formed and accumulates. This condition is called 

 urcemia, and unless the urea be discharged from the body the patient 

 dies in a condition of coma preceded by convulsions. 



Urcemia. This term was originally applied on the erroneous supposition that it 

 is urea or some antecedent of urea which acts as the poison. There is no doubt 

 that the poison is not any constituent of normal urine ; if the kidneys of an animal 

 are extirpated, the animal dies in a few days, but there are no symptoms of uraemia. 

 In man, also, if the kidneys are healthy or approximately so, and suppression of 

 urine occurs from the simultaneous blocking of both renal arteries by clot, or of both 

 ureters by stones, again uraemia does not follow. On the other hand, uraemia may 

 occur even while a patient with diseased kidneys is passing a considerable amount 

 of urine. What the poison is that is responsible for the convulsions and coma, is 

 unknown. It is doubtless some abnormal katabolic product, but whether this is 

 produced by the diseased kidney cells, or in some other part of the body, is also 

 unknown. 



Where, then, is the seat of urea formation ? Nitrogenous waste 

 occurs in all the living tissues, and the principal final result of this 

 proteid metabolism is urea. It may not be that the formation of 

 urea is perfected in each tissue, for if we look to the most abundant 

 tissue, the muscular tissue, urea is absent, or nearly so. Yet there 

 can be no doubt that the chief place from which urea ultimately 

 comes is the muscular tissue. Some intermediate step occurs in the 

 muscles ; the final steps occur elsewhere. 



In muscles we find a substance called creatine in fairly large 

 quantities. If creatine is injected into the blood it is discharged 

 as creatinine. But there is very little creatinine in normal urine ; 

 what little there is can be nearly all accounted for by the creatine in 

 the food ; the muscular creatine is discharged as urea ; moreover, 

 urea can be artificially obtained from creatine in the laboratory. 



Similarly, other cellular organs, spleen, lymphatic glands, 

 secreting glands, participate in the formation of urea ; but the most 

 important appears to be the liver : this is the organ where the final 

 changes take place. The urea is then carried by the blood to the 

 kidney, and is there excreted. 



The facts of experiment and of pathology point very strongly 



