Muscular exertion in man leads to an increase in the quantity of lactic acid in both blood2 and urine,3 due, in all probability, to slight local anemia in the muscles. (See p. 322).

The consideration of the subject of subnormal oxygen supply may first be considered in connection with bloodletting, which produces an artificial anemia. Bauer,4 in Voit's laboratory, was the first to study this systematically, and found that the immediate result of bloodletting in the dog was an increased protein metabolism, but that the carbon dioxid elimination was unchanged; 18 to 27 per cent, of the total blood in the body was removed in these experiments.

Hawk and Gies5 confirm the reports of a higher protein metabolism after bloodletting.

Finkler,6 in Pfluger's laboratory, withdrew one-third of the total blood from a dog, thereby reducing the rapidity of blood-flow in the femoral artery by one-half, and yet there was no change in the quantity of oxygen absorbed, and, therefore, of the quantity of the carbon dioxid exhaled. Finkler noted, however, that the quantity of oxygen in the venous blood grew constantly less after repeated bleedings. This indicates the interrelation between the oxygen supply and the needs of the tissues. Under ordinary circumstances there are 20 volumes per cent, of oxygen in the arterial blood, of which 12 volumes per cent, may return as an unused excess to the right heart.

1 Zuntz: "Die Kraftleistung des Tierkorpers," Festrede, Berlin, 1908, p. 18.

2 Fries: "Biochemische Zeitschrift," 1911, xxxv, 368.

3 Spiro: "Zeitschrift fur physiologische Chemie," 1877, i, in; Ryffel: "Journal of Physiology," 1909-10, xxxix, p. xxix.

4 Bauer: "Zeitschrift fur Biologie," 1872, viii, 567.

5 Hawk and Gies: "American Journal of Physiology," 1904, xi, 226. 6 Finkler: "Pfluger's Archiv," 1875, x, 368.

Repeated bleedings by Finkler reduced this percentage in venous blood from 11.80 per cent, to 8.80, 4.06, and 2.71 per cent. The carbon dioxid content of the blood remained unchanged. This decrease in the oxygen content of the blood may stimulate both the heart and respiration to compensatory activity, although nothing resembling asphyxia be present. While the total heat production is unchanged in anemia following bloodletting (except as influenced by increased cardiac and respiratory activity), still it is evident from the diminution of oxygen present in venous blood that there would not be a sufficient supply of oxygen to provide for a largely increased metabolism. Hence the anemic organism is incapable of great muscular work without quick exhaustion accompanied by rapid respiration and heart-beat. These latter are further efforts of compensation for the decrease in the oxygen-carrying elements of the blood.

The removal of blood from a dog, followed by the transfusion of an equal quantity, has no effect upon metabolism,1 although if an artificial plethora be induced by the intravenous injection of fresh blood into a normal animal, the metabolism is slightly increased, a result which is probably due to increased heart action.2

After bloodletting of any considerable magnitude, lactic acid and, it is reported, a small amount of sugar appear in the urine. Thus Araki3 found lactic acid in the urine of rabbits which had been bled. He also found lactic acid in the urine of rabbits which had been exposed to the action of rarefied air, and he found lactic acid and glucose in the urine of animals the oxygen-carrying capacity of whose blood had been diminished through the respiration of carbon monoxid. It should be noticed in passing that wherever lactic acid is formed in the organism there is a concomitant rise in protein metabolism. Since this lactic acid is a derivative of glucose, its non-combustion may raise the protein metabolism to a higher level, just as is the case when sugar remains unburned in diabetes.

1 Pembrey and Gurber: "Journal of Physiology," 1894, xv, 449.

2 Hari: "Biochemische Zeitschrift," 1911, xxxiv, III; 1912, xliv, 1.

3 Araki: "Zeitschrift fur physiologische Chemie," 1894, xix, 424.

In experimental anemias the hemoglobin content of the blood of rabbits1 or dogs2 may be reduced to 20 per cent, of the normal amount, with indications of only slight changes in the intensity of the oxidative processes, and these are usually in the direction of slight increases. Such increases one may interpret as being derived from the rise in protein metabolism and as due to stimulation of the cells by lactic acid (see p. 298).

Another fact which has been observed by Lewinstein3 is that when rabbits are kept in a bell-jar at a barometric pressure of 300 to 400 mm. (corresponding to 5000 to 7500 meters above sea-level) they die on the second or third day, and autopsy reveals extreme fatty infiltration of heart, liver, kidney, and diaphragm. These animals took no food. The cause of this fatty change, in the present writer's opinion, was the lessened combustion of sugar or its derivative, lactic acid, which always induces an abnormal deposit of fat in any sugar-hungry cells (p. 490).

Kohler4 artificially compressed the trachea of rabbits by tying a lead wire around it. The animals recovered from the operation and lived for four weeks in a condition of dyspnea. Appetite, weight, urine, and body temperature remained normal almost until the end. The dyspnea was apparently insufficient to affect the metabolism. Increased respiration and heart activity were effectual efforts at compensation, so that there was no lack of oxygen in the animals. However, the altered pressure in the lungs and the continued dyspnea brought about a condition of stasis of which the animal died. The secondary alterations were acute and wide-spread, and were hyperemia of the lungs, vesicular and intralobular emphysema of the lungs, and hypertrophy of both sides of the heart.

1 Eberstadt: "Archiv fur exp. Path, und Pharm.," 1913, lxxi, 329.

2 Roily: "Deutsches Archiv fur klinische Medizin," 1914, cxiv, 605. 3 Lewinstein: "Pfluger's Archiv," 1897, lxv, 278.

4 Kohler: "Archiv fur exp. Path, und Pharm.,' 1877, vii, 1.