PHYSIOLOGY OF RESPIRATION. 



visionally at least. We may believe that in the metabolism of the 

 nerve cells constituting the center, as in the metabolism of the 

 muscle, certain organic acids, such as lactic acid, are formed which 

 in the presence of a normal supply of oxygen are further oxidized. 

 When, however, the oxygen supply is insufficient these acids may 

 accumulate and serve as a stimulus, either directly or indirectly, 

 by making the cells more irritable to the effect of the carbon 

 dioxid.* This point of view enables us to understand also some 

 interesting results of the effect of breathing oxygen. When one 

 holds his breath the carbon dioxid tension in the blood increases, 

 and eventually the stimulus becomes so strong that respirations 

 ensue in spite of the strongest effort to inhibit them. This ' 'break- 

 ing point" is reached f in 23 to 77 seconds after the carbon dioxid 

 in the alveoli of the lungs has reached a concentration of 6.2 to 7.5 

 per cent., and the oxygen is reduced to 9 to 11 per cent. If before 

 holding the breath the lungs are filled with oxygen by taking several 

 breaths of the pure gas, the breaking point may be prolonged to 

 as much as 160 seconds, and one observer (Vernon) reports that if 

 the lungs are first thoroughly aerated by forced breathing, so as 

 to wash out the carbon dioxid in the alveoli, and at the end pure 

 oxygen is breathed in, the breaking point may be deferred as long 

 as eight minutes. Evidently, therefore, an accumulation of 

 carbon dioxid in the blood, as indicated by the composition of the 

 alveolar air, is less efficient as a stimulus to the center when an 

 adequate supply of oxygen is provided, and this fact may be ex- 

 plained on the hypothesis that the oxygen prevents the accumula- 

 tion of the acid products of metabolism. 



The two fundamental facts that the respiratory center is stimulated by 

 excess of carbon dioxid and by deficiency of oxygen have been brought together 

 by an hypothesis which assumes that the resulting effect is the same in both 

 cases. J According to this view the carbon dioxid does not stimulate the center 

 directly, but indirectly, because like any other acid in solution, it gives rise to 

 the production of hydrogen ions, and these ions constitute a stimulus which 

 begins to be effective when their concentration passes a certain threshold value. 

 Lack of oxygen brings about the same increase in concentration of hydrogen 

 ions owing to the fact that it permits the accumulation of acid products of 

 intermediary metabolism, products which under normal conditions are re- 

 moved by oxidation. If this view proves to be correct, it is obvious that it 

 implies further that the activity of the respiratory center constitutes an efficient 

 means for preserving the neutrality of the blood, since in proportion as the 

 carbon dioxid concentration, and therefore the hydrogen-ion concentration, 

 increases in the blood the respiratory center will be stimulated. The greater 

 respiratory movements thereby produced will tend to remove the excess of 

 carbon dioxid. A further problem in connection with the action of the respira- 

 tory center is the cause of its rhythmic activity. The underlying mechanism 

 of this rhythmicity is obscure, but it is possible that in this instance, as in 



* Haldane and Poulton, "Journal of Physiology," 37, 390, 1908. 

 t Hill and Flack, "Journal of Physiology," 37, 77, 1908. 

 i Winterstein, "Pfliiger's Archiv," 138, 167, 1911. 



