As indicated above there may be an auto intoxication from the retention of the excreta, more particularly those eliminated by the kidneys. Whilst the normal metabolism of the tissues produces leucomaines in small amounts which are promptly excreted, there may be, on the one hand, an increased production, and, on the other hand, a defective excretion. A third contingency has to be added, namely, an alteration in the process of metabolism. These various conditions give rise to different forms of disease.