The quantity of ammonia, though it presents a clear gain of so much alkali for the body, does not appear to vary for purposes of regulating the reaction of the blood. The main regulation is accomplished by the elimination of acid phosphate and carbon dioxid. Only in pathologic conditions with acid formation is ammonia drawn upon for purposes of regulation.

The body's reserves of alkali are considerable, and replenishment is usually accomplished through alkalis contained in the food (see p. 361).

According to Michaelis,4 the reaction of the fluid which may be expressed from fresh tissues and thrown in boiling water to prevent postmortal acid formation is not alkaline like blood, but is almost exactly neutral.

Bearing in mind the fundamental factors presented above, one may now consider the actual results of administering acids or alkalies upon the composition of the urine and blood.

In the first place, it was shown by Haldane and Priestley5 that a very small increase in the tension of carbon dioxid in the alveolar air was accompanied by a stimulation of the respiratory center. Krogh and Krogh6 proved that the tension of carbon dioxid in the alveoli closely follows that of arterial blood. Finally, Hasselbalch4 showed that in reality an increase in the hydrogen ion concentration of the blood was the real stimulus to respiration, and thus caused the blood to be automatically relieved of excess of acid ions existing in the form of HCO3. In experiments he showed that when an acid urine was being secreted the C02 tension of the alveolar air was lowered, indicating increased acid in the blood. A diet which produced a less acid or an alkaline urine increased the CO2 tension of the alveolar air, indicating a larger content of alkali in the blood.

1 Henderson, L. J., and Palmer: "Journal of Biological Chemistry," 1913 xiv, 81.

2 Henderson and Palmer: Ibid., 1914, xvii, 305. 3 Blatherwick: Ibid., 1914, xvii, p. xl.

4 Michaelis and Kramsztyk: "Biochemische Zeitschrift," 1914, lxii, 180. 5 Haldane and Priestley: "Journal of Physiology," 1905, xxxii, 225. 6Krogh and Krogh: "Skan. Archiv fur Physiologie," 1910, xxiii, 179.

The figures for one experiment may be here reproduced:

In another experiment a larger volume of respiration was found to accompany the lower alveolar C02 tension, as follows:

These results demonstrate that C02 acts only indirectly upon the respiratory center. For the maintenance of a constant reaction of the blood, more C02 is required in the presence of alkali than in the presence of acid. The variation in the ventilation of the lungs, brought about by the sensitiveness of the respiratory center to H ions controls the C02 tension in the alveoli, so that the reaction of the blood remains practically-unchanged under the two given different dietary conditions.

'Hasselbalch: "Biochemische Zeitschrift," 1912, xlvi, 403.

It is only in exceptional cases that in the normal life of a man at rest the diurnal variation in the carbon dioxid tension of the alveoli exceeds the equivalent of 2 mm. of mercury.1

The administration of acid to such an extent that the reaction of the blood becomes acid produces death. Such blood cannot combine with carbon dioxid. Thus, after giving 90 c.c. of half-normal hydrochloric acid intravenously to a dog, death resulted in virtue of the production of an experimental acidosis, the PH equalling 6.9 in the blood.2 The reduction of carbonic acid in the blood of a rabbit from 45 volumes per cent, to 10.1 per cent., with accompanying dyspnea, was observed by Loewy and Munzer3 after the administration of 0.72 gram of hydrochloric acid per kilogram of body weight, and Porges4 has noted that intravenous injection of monosodic phosphate into a narcotized rabbit raises the respiratory quotient from 0.68 to 0.79, indicating the elimination of carbon dioxid from the plasma.

If, however, acid in moderate quantity is given with food, increased ammonia production may neutralize the acid given.

This has been beautifully shown with calves,5 as appears in the following experiment:

Calf: Weight, 100 Kg.; Food, 9.1 Kg. Of Milk Daily

1 Erdt: "Deutsches Archiv fur klinische Medizin," 1915, cxvii, 497; Hig-gins, "American Journal of Physiology," 1914, xxxiv, 114.

2 Levy, Rowntree, and Marriott: "Archives of Internal Medicine," 1915, xvi, 389.

3 Loewy and Munzer: "Archiv fur Physiologie," 1901, 81.

4 Porges: "Biochemische Zeitschrift," 1912, xlvi, 1.

5 Steenbock, Nelson, and Hart: "Journal of Biological Chemistry," 1914, xix, 399.

Only when the larger quantities of acid were administered did it appear that the bones were attacked, and this was at the expense of their calcium carbonate content. The administration of acid did not prevent the growth and development of the calf.

In man hydrochloric acid may be given with a similar protective rise of ammonia, as appears below:1

Consequence Of Adding Hydrochloric Acid To The Diet Of Man. Daily Averages

In the above experiment 85 c.c. of a solution containing 12 per cent, or 10.2 grams of chlorin was added to the food during three days, being an average of 3.4 grams of chlorin per day. This would require 1.6 grams of ammonia to effect its neutralization. On the third day of acid administration the ammonia rose to an output of 2.03 grams. The phosphates increased 12 per cent, and there was a rise in the acidity of the urine. As the result of these protective agencies the carbon dioxid tension in the blood remained unchanged after the administration of hydrochloric acid.

In certain pathologic states, such as diabetes, phosphorus-poisoning, nephritis in some of its forms, the so-called food intoxication of infants,2 and other conditions, there is an increased production of ammonia in the body for the neutralization of acids of endogenous origin. This may be accompanied by a withdrawal of body alkali, so that the power to combine with carbon dioxid is greatly reduced and the alveolar tension of C02 falls in consequence. However, even under these conditions the reaction of the blood may remain unaffected. This is strikingly illustrated in the experiments of Poulton1 on cases suffering from severe diabetes, in which condition β-oxy-butyric acid is largely formed. (See table, p. 468).

1 Begun, Herrmann, and Munzer: "Biochemische Zeitschrift," 1915, lxxi, 255.

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