EXPERIMENTAL ACUTE NEPHRITIS: THE VASCULAR REACTIONS AND THE ELIMINATION OF NITROGEN

By combining physiological and anatomical methods in the study of experimental nephritis it is possible to distinguish types of nephritis in which either tubular or vascular changes predominate, and are essentially characteristic of the lesion produced, but it is not possible to say that a given poison produces exclusively tubular or exclusively vascular lesions. The so-called epithelial poisons (potassium chromate, uranium nitrate and corrosive sublimate) present anatomical evidence of extensive tubular injury, and in the early stages show, on physiological study, no evidence of vascular injury other than exaggerated contraction and dilatation of the vessels and increased diuresis. On the other hand, the vascular poisons, arsenic and cantharidin, which produce but little injury to the tubules, tend to cause anuria and are characterized by minimal contraction and dilatation of the vessels and little or no flow of urine. From the physiological point of view these two types may be, for practical purposes, considered as examples of tubular and vascular nephritis. They are not, however, pure types; for the increased diuresis of the early tubular type is in itself evidence of vessel irritability and similar to the increased irritability caused by small doses of vascular poisons, and on the other hand, this essentially vascular lesion is accompanied by slight morphological changes in the tubular epithelium. Furthermore, the tubular lesions of chromium and uranium and corrosive sublimate pass into a stage closely resembling the vascular type, if not identical with it. Two forms of late tubular nephritis may be recognized. One of these, the anuric form, is accompanied by severe gastro-intestinal disturbance and evidence of approaching anuria; physiological tests show diminished power of dilatation of the vessels and corresponding inhibition of diuresis. The second form, the polyuric, is characterized by a condition of polyuria up to the moment of anesthesia; physiological tests show that the power of dilatation is retained, but little or no diuresis occurs. Whether the vascular incompetency of the anuric form of late tubular lesions is a natural consequence of the vessel irritability seen in the early stages or is the result of the elimination of secondary poisons through the glomeruli cannot be absolutely determined. The peculiar impermeability of the glomerulus following anesthetization in the polyuric form, which is essentially a stage of recovery, we hope to explain by investigations now in progress. Studies of the elimination of nitrogen show that in tubular nephritis, as represented by uranium nephritis, the output of nitrogen is considerably diminished. This apparently occurs also in chromate nephritis but is not clearly demonstrated. In both forms the onset of gastro-intestinal disturbances appears to bear a definite relation to the retention of nitrogen. On the other hand, as the nitrogen of the feces is not appreciably altered, these disturbances cannot be explained by the elimination through the intestine of toxic bodies of nitrogenous nature. The nitrogen elimination in the urine in vascular nephritis as represented by arsenic nephritis is not only not diminished but is greatly increased as the result of the increased metabolism caused by arsenic. If at the height of this increased elimination, uranium nitrate is administered, the nitrogen output is markedly diminished. These observations demonstrate that not only are the tubular lesions in arsenic nephritis of little moment, but also that serious injury of the epithelium, as that due to uranium, may cause a temporary nitrogen retention. A consideration of all the facts here presented allows us to conclude that although it is not possible to demonstrate that an experimental nephritis may be purely tubular or purely vascular, which is in accord with our clinical and pathological studies of human material, it is possible, if we combine the results of anatomical, physiological and chemical study, to recognize lesions which are predominantly tubular or vascular, or which change rather sharply from one to the other type, and are, therefore, of great value in the study of the problems of nephritis.