704 PHYSIOLOGY OF RESPIRATION. 



stitutes the normal stimulus to the respiratory center and that the 

 activity of this center varies proportionately to the concentration of 

 the carbon dioxid in the blood, the question has arisen whether the 

 carbon dioxid acts directly as a stimulus or in virtue of its effect 

 in increasing the acidity or hydrogen ion concentration of the 

 blood. The CO 2 in solution forms carbonic acid, H 2 CO 3 , which dis- 

 sociates to yield hydrogen ions. Acids added to the blood experi- 

 mentally or formed in the body, as in conditions of acidosis, stimu- 

 late the center, and a number of observers* have concluded, there- 

 fore, that the stimulus to the center is, in reality, the hydrogen-ion 

 content of the blood. An increase in carbon dioxid concentration 

 such as occurs in muscular exercise would tend to increase the hy- 

 drogen-ion concentration and thus its stimulating effect is explained. 

 The mechanism works automatically in the direction of keeping the 

 reaction of the blood normal, since an increase of acidity by stimu- 

 lating the center and causing an increased ventilation of the lungs 

 tends to reduce the carbon dioxid pressure. In correspondence 

 with this conclusion it is found that in acidosis caused by an increase 

 in the fixed acids of the blood there is a noticeable diminution in the 

 carbon dioxid pressure in the alveolar air. In fact, diminished car- 

 bon dioxid pressure in the alveolar air has been considered as one 

 of the diagnostic indications of a condition of acidosis. f While 

 there can be no doubt of the general fact that the activity of the 

 respiratory center is sensitive to the reaction or hydrogen-ion con- 

 centration of the blood, and that in consequence this center, by its 

 influence upon the breathing and the composition of the alveolar air, 

 serves to regulate the normal reaction of the blood, there is still 

 some question as to whether the effect of carbon dioxid upon the 

 center is wholly due to its influence in raising the hydrogen-ion con- 

 centration. In some direct experiments made upon the isolated 

 mammalian medulla perfused with defibrinated blood t it was found, 

 in accordance with the above view, that any increase in the al- 

 kalinity of the blood tends to depress the activity of the respira- 

 tory center, and vice versa. But it is also stated that a high press- 

 ure of carbon dioxid in the perfused blood stimulates the center to a 

 greater degree than a blood of the same hydrogen-ion concentra- 

 tion, but with a low tension of carbon dioxid. This last result 

 indicates that the carbon dioxid may have a specific stimulating 

 effect on the center; but whatever may be its mode of action, it 

 seems certain that the concentration of carbon dioxid in the blood 

 controls the activity of the respiratory center under normal condi- 

 tions. Lack of oxygen, as we have seen, may also stimulate the 



* Haldane, loc. tit.; Winterstein, "Pfliiger's Archiv," 138, 167, 1911. 

 t Marriott and Howland. 



j Hooker, Wilson, and Connett, "American Journal of Physiology/' 43, 

 351, 1917. 



