The effect of copious drinking of water upon protein metabolism has been made the subject of various studies. A small increase in nitrogen elimination has usually been noted. This was first established by Voit, who explained it as due to an increased circulation which influenced the flow of the intracellular fluids. Heilner2 has shown that giving 2000 c.c. of water to a fasting dog on two successive days raises his urinary nitrogen from 3.15 grams to 4.09 and 3.58 grams on the two days of water ingestion, and then the nitrogen excretion falls to 2.22 and 2.62 on the following days. In this experiment the carbon dioxid excretion was very slightly increased and the temperature of the dog was not affected. The quantity of urine rose from 90 to 2050 c.c.

Straub3 found that an extra ingestion of 2000 c.c. of water in a man who was in nitrogen equilibrium on a diet containing 20.56 grams of nitrogen had no effect on protein metabolism; whereas Hawk,4 who gave less protein nitrogen but more water, found that the ingestion of 4500 c.c. of water caused the urinary nitrogen to rise from 11.03 to 12.48 on the first day, and 11.82 on the second day, with a fall to 10.91 grams on the succeeding day when no water was given. Hawk interprets the action of copious water drinking as twofold: first, to cause a removal of any accumulation of nitrogenous decomposition products from the organism, as was indicated by the greater increase of 12.8 per cent, in the nitrogen elimination of the first day; and, second, to cause a true increase in protein metabolism, as was indicated by the smaller increase of 6.8 per cent, on the second day of water ingestion.

1 Wells: Proceedings of the Society for Experimental Biology and Medicine, 1908, vi, 1.

2 Heilner: "Zeitschrift fur Biologie," 1906, xlvii, 541.

3 Straub: Ibid., 1899, xxxvii, 527.

4Hawk: "University of Pennsylvania Medical Bulletin," March, 1905.

Abderhalden and Bloch4 have given a fixed diet to a person suffering from alkaptonuria (see p. 178) and on one of the days of the experiment have caused him to ingest 5 liters of water. The results of their analyses gave the following figures:

Abderhalden believes that the constancy of the output of homogentisic acid indicates a constancy of protein metabolism throughout, whereas the rise in total nitrogen elimination in the urine represents a washing out of the nitrogenous end-products as a result of the large ingestion of water.

One of the striking characteristics of starvation metabolism was shown to be its extreme regularity from hour to hour and from day to day. What, then, is the hour-to-hour metabolism after meat ingestion?

The classical experiments of Voit2 and of Feder3 have been more fully worked over by Gruber. Gruber4 fed a dog with 500, 1000, and 1500 grams of meat on different days. He collected the urine every two hours after the meal and determined the nitrogen output. The curves of nitrogen elimination under these circumstances are as follows:

1 Abderhalden and Bloch: "Zeitschrift fur physiologische Chemie," 1907, liii, 464.

2 Voit: "Physiologische Untersuchungen," Augsburg, 1857, p. 42.

3 Feder: "Zeitschrift fur Biologie," 1881, xvii, 541.

4 Gruber: Ibid., 1901, xlii, 421. '

Fig. 12. - 1, After 500 g. meat + 50 g. fat + 350 c.c. water; 2, after 1000 g. meat + 200 c.c. water; 3, after 1500 g. meat + 500 c.c. water. On each of these days the animal was in nitrogen equilibrium.

It is evident that there is an early elimination of protein nitrogen which here reaches a maximum between five and seven hours after feeding, and that the hour of the maximum excretion is delayed by increasing the quantity of meat ingested.

It is apparent, therefore, that the protein metabolism as illustrated by the curve of nitrogen elimination is quite different from its even metabolism in starvation.

Haas1 in experiments on man finds that the curve of nitrogen elimination after a breakfast consisting of milk, bread, butter, and cheese always shows two maxima, the first in the second hour and the second in the fifth. The first rise in the curve is due to the removal of nitrogenous end-products already in the system and is caused by the early absorption of liquids taken with the food. The second rise corresponds to the absorption of food protein. Haas believes this to be the true explanation, because if diuresis be first induced by drinking tea, with a consequent washing out of urea from the body, then partaking of breakfast no longer causes so high a primary rise of nitrogen elimination, nor is the total elimination so great as in the experiments without preliminary diuresis. The experiment shows that for short periods the nitrogen excretion is not a true index of urea production. Severe muscular work has no influence upon the character of the curve described except when the quantity of urine produced is diminished, in which case the urea elimination is also reduced.

1 Haas: "Biocbemische Zeitschrift," 1908, xii, 203.

Confirming Albarran,1 Barringer and Barringer2 note that the volumes and the nitrogen content of the urine from the two kidneys are almost identical.

Urea in the organism undergoes no chemical change; there is no reversible reaction in the sense of ammonia formation.3 When urea is retained in the body it is found widely distributed in all the tissues excepting fatty tissue; if it be administered intravenously to a dog diffusion to all parts of the body is complete in a few minutes.4 A concentration of 1.2 per cent, may sometimes be reached in the dog, though one of over 1 per cent, is usually fatal.