METABOLISM IN NEPHRITIS 385 



Even though these disturbances occur in the course of a nephritis it 

 can not be accepted as proved that they depend upon the renal disease and 

 it is also perfectly evident that the pathologicophysiological process at 

 fault is not explained. Uremic manifestations occur in all sort of renal 

 conditions. However, it appears that the majority of instances of uremia 

 accompany kidney disease in which there is a diminished excretion of 

 water and of solid substances. Acute nephritis, chronic nephritis, bilateral 

 obstruction of the ureters, impermeable urethral strictures, eclampsia, 

 cholera and, in fact, all conditions in which the urinary secretion is very 

 much diminished, or lacking entirely, fall in this category. 



Animals in which anuria is effected in various ways, by ligature of the 

 renal arteries or of the ureters, or by double nephrectomy, succumb in a 

 lew days. \ r omiting, diarrhea, apathy, somnolence, coma and death are 

 the main symptoms. Convulsive seizures do not occur. 



Voit(cf) showed that urea accumulated in the blood and tissues of such 

 animals. It is tempting to assume that this is the causative agent respon- 

 sible for the poisoning. Injection experiments, however, prove that this 

 is not the case. Neither the venous infusion of urine nor solutions of urea 

 apparently produced any pathological manifestations (consult Frerichs 

 (&)). Furthermore, it was found that the blood urea is not necessarily 

 high when uremia occurs. Frerichs elaborated the idea of the toxicity of 

 urea by attributing the uremic symptoms to ammonium carbamate which 

 he believed to be derived from urea through the action of a ferment. At 

 present, however, it is established that neither this substance nor ammonia 

 occurs in the body under normal circumstances or when uremia exists and 

 Frerichs' brilliant idea must therefore be dropped. 



Chemical theories evidently have not been adequate to account for 

 uremia ; other efforts in this direction have not been any more successful, 

 but some of them will be mentioned. A number of authors, who were es- 

 pecially anxious to account for the nervous manifestations of uremia, 

 have attached much importance to inflammatory changes of the cerebral 

 meninges (Osborne), and to congestion of the brain, and finally Traube 

 proposed a theory which was well thought out in certain directions and 

 rather vague in others. He proposed to explain the occurrence of coma 

 by edema of the midbrain ; the edema was supposed to depend on two fac- 

 tors, the increased arterial pressure and the disturbed osmotic relations 

 entailed by the diminished protein content of the blood. All experimental 

 evidence, even after enormous infusions of saline solution, fails to con- 

 firm either contention ; neither an increased blood pressure nor a marked 

 hydremia will bring about cerebral edema. It is not necessary to discuss 

 this theory in greater detail because cerebral edema is not constantly pres- 

 ent in uremic subjects. I can assure you, that in the two decades that have 

 passed since Traube published his ideas, I have examined many brains 

 of those dying with uremia, and found them to be normal in every way. 



