In 1821 Prevost and Dumas1 observed that if the kidneys of a dog be extirpated, urea accumulates in the blood. This observation led to the discovery by Bright in 1836 that the amount of urea in the blood of nephritic patients was abnormally high.

Using more accurate methods, Folin2 finds that when a low protein dietary is taken the normal figures for total non-protein nitrogen in the blood of a man are 22 to 28 milligrams per 100 c.c. of blood, of which 11 to 14 milligrams are in the form of urea. The maximum amount of non-protein nitrogen in a normal person is not usually above 40 milligrams per 100 c.c.3 Sometimes after protein ingestion in nephritis the non-protein nitrogen does not increase in the blood; in other cases there is a considerable rise. The increased level of urea in the blood is a compensatory reaction to a diminished power of excretion by the kidney.4

Emphasis has been laid upon a negative nitrogen balance as indicating a retention of urea by the nephritic patient, but such a retention is susceptible of two interpretations. Thus, Mosenthal and Richards5 have given patients with moderately severe chronic interstitial nephritis diets containing between 16 and 47 grams of nitrogen and have observed nitrogen retention. Had this retention been in the form of non-protein nitrogen, the blood would have contained between 78 and 148 milligrams of such nitrogen, but the actual values never rose above 38 milligrams. Davis and Foster,1 however, find that nitrogen retention under these circumstances may take place in the liver and muscle in the form of non-protein nitrogen. The very ill patients were benefited by large water ingestion.

1 Prevost and Dumas: "Ann. de chemie et de phys.," 1821, xxiii, 90.

2 Folin, Denis, and Seymour: "Archives of Internal Medicine," 1914, xiii, 224.

3 For the complete chemical and physical analysis of blood in 30 normal cases consult the important work of Gettler and Baker: "Journal of Biological Chemistry," 1916, xxv, 211.

4 McLean: "Journal of Experimental Medicine," 1915, xxii, 366.

5 Mosenthal and Richards: "Archives of Internal Medicine," 1916, xvii, 329.

Henderson and Palmer2 describe cases of nephritis in which the volume of the urine is large, the titratable acidity high, but in which the total acid elimination is decreased because of a greatly reduced elimination of ammonia. They conclude that this points to a condition of acidosis of renal origin. As a matter of fact, Peabody3 .has discovered that the acidosis of nephritis is due to a retention of non-volatile acids which would ordinarily be removed by the kidney.

Peabody, Aub, and DuBois, in experiments yet to be published, have made investigations concerning the metabolism of 10 patients suffering from severe nephritis which show that most of the individuals had normal basal metabolisms. In the presence of greatly decreased alkalinity and of a high content of non-protein nitrogen in the blood the total heat production showed no variation from the normal.

Tachau4 finds that in nephritis the loss of nitrogen by way of the sweat induced by an electric light bath is not material, but that the loss of sodium chlorid may reach 2 grams per hour and may reduce an edema.

In patients who manifest marked evidence of circulatory disturbances Foster6 shows that there is an increase in the quantity of non-protein nitrogen of the blood, even in the absence of nephritis.

1 Davis and Foster: "Proceedings of Soc. for ex. Biol, and Med.," 1915, xiii, 33.

2 Henderson, L. J., and Palmer: "Journal of Biological Chemistry," 1915, xxi, 37.

3 Peabody: "Archives of Internal Medicine," 1914, xiv, 236; Ibid., 1915, xvi, 955.

4 Tachau: "Deutsches Archiv fur klinische Median," 1912, cvii, 305. 5 Foster, N. B.: "Archives of Internal Medicine," 1915, xv, 356.

Peabody, Meyer, and DuBois1 studied 16 patients with cardiac and cardiorenal disease by the methods of direct and indirect calorimetry. The two methods agreed within 1.9 per cent. There was no abnormal deviation of the respiratory quotients as had been announced by several previous investigators. Patients with compensated cardiac lesions or with mild nephritis showed a normal metabolism. Of 12 patients with dyspnea, 9 showed a distinct rise in metabolism, and in 5 of these the increase was between 25 and 50 per cent, above the normal. Two of these 5 patients manifested marked acidosis, as was indicated by a low carbon dioxid tension in the alveolar air. In 2 other patients, whose metabolisms were equally high, there was no significant depression of the alveolar carbon dioxid.

If the dyspnea were accompanied by the production of lactic acid in any of the organs, this might have been the stimulus to the higher metabolism observed. The decompensated heart produces slow or insufficient circulation with imperfect oxidation in the tissues, which conditions readily lend themselves to lactic acid formation.

Howland and Marriott2 describe a type of acidosis which occurs in infants during the course of attacks of severe diarrhea not of ileocolitic type. The usual type of abdominal breathing of the young child is succeeded by one which is both costal and abdominal. There is a greater amplitude in the respirations and they are made with a distinct effort. There is no cyanosis. The condition was first described by Czerny3 who called attention to the symptoms as resembling those observed in rabbits dying after the administration of mineral acids. Howland and Marriott find that a condition of acidosis is actually present in these children and they were the first to use alkaline treatment in order to rescue them. The acidosis is not due to acetone bodies, from which the blood is free. The following presents the results of treatment in one of their cases:

1 Peabody, Meyer, A. L., and DuBois: "Archives of Internal Medicine," 1916, xvii, 980. • •

2 Howland and Marriott: "American Journal of Diseases of Children," 1916, xi, 309.

3 Czerny: "Jahrbuch fur Kinderheilkunde," 1897, xlv, 271.

In normal infants the carbon dioxid tension is between 36 and 45 mm. and the PH of the blood is 7.4. In the children with acidosis the PH of the blood was 7.2. There was also a reduction of the reserve alkali of the blood. There was frequent anuria and the conclusion is drawn that the cause of the acidosis is probably a retention of acid phosphate in the organism.