REGULATION OF RESPIRATORY MOVEMENTS 1087 



starvation there was an excessive production of lactic acid in the body, and we have 

 seen that the same is true for the isolated muscle and that to these substances has been 

 ascribed (Zuntz and Geppert) the excitation of the respiratory centre which occurs in 

 violent muscular exercise. Haldane has suggested that in the hyperpnoea and con- 

 vulsions which occur as the result of breathing mixtures with very low percentages of 

 oxygen the effective stimulus is also lactic acid. Experiments were carried out by 

 Ryffel on individuals who had been subjected in a respiratory chamber to very low 

 oxygen tensions, sufficient to cause cyanosis, so that their oxygen alveolar tension was 

 only about 6 per cent. After an experiment, lasting four hours, there was a definite 

 increase of lactic acid in the blood of the fore arm (up to 23-6 mg. lactic acid per 100 c.c.). 

 After one lasting only fifteen minutes, in which the oxygen shortage became very 

 marked, no increase could be detected. When we expose an animal such as a rabbit to 

 low percentages of oxygen, the hyperpnoea so produced disappears almost immediately 

 when a larger percentage of oxygen is supplied to the animal, whereas that produced by 

 carbon dioxide excess dies away slowly on exposure to normal conditions. It would seem 

 that when the exposure to low oxygen tensions is of short duration no lactic acid is pro- 

 duced in the blood. If therefore we ascribe the hyperpncea to the production of lactic ac 'd 

 we must locate the production of this acid in the respiratory centre itself. There are no 

 inherent improbabilities in such an assumption, but it is difficult at present to see how 

 it can be put to the test of experiment. 



In dealing with" the question of the blood alkalinity we defined neutrality as a con- 

 dition in which there were equivalent concentration of H and OH ions. In the blood 

 the H ion concentration is about 0'3 x 10~ 7 N. The alkalinity is expressed by 



concentration OH ions 



: 7 . The acids and bases of the blood -serum and of the tissue-fluids 



concentration H ions 



generally are in such proportions as to maintain the approximate neutrality of these 

 fluids even after considerable additions of acid or alkali. This hydrochloric acid may 

 be added to the extent of -025 N, or NaOH to the extent of -005 N, without causing any 

 marked alteration in the reaction of the blood. Although, however, the change pro- 

 duced by the addition of acids or alkalies is so minute, it is appreciable by electrical 

 methods, and it may still more readily be appreciated by and act as a stimulus for the 

 cells of the body themselves. Thus we have not yet succeeded in determining electric- 

 ally the change in hydrogen ion concentration caused by the change from arterial to 

 venous blood. If, however, blood-serum be saturated with carbon dioxide at a full 

 atmosphere, the concentration of the hydrogen ions rises to 1 -4 x 10~ 7 N, while after re- 

 moving the greater part of the carbon dioxide from the same serum by the passage of a 

 stream of air, the concentration of the hydrogen ions sinks to -008 x 10~ 7 N. As the 

 respiratory centre responds to such minute changes of concentration as would be X 

 pressed by a difference of 0*2 per cent, of an atmosphere in the carbon dioxide tension 

 of the circulating blood, it must possess a sensitivity greater than any of our physical 

 means for measuring the concentration of hydrogen ions in a fluid. We may approach 

 this delicacy of reaction by using a large molecule as our indicator. Thus, as we have 

 seen, the dissociation curve of haemoglobin is sensitive to the change in reaction caused 

 by raising the tension of carbon dioxide in the haemoglobin solution by 10 mm. Hg. 

 (cp. Fig. 497). 



The regulating factor in the blood is probably not carbon dioxide nor any special acid, 

 but the concentration of hydrogen ions in this fluid or in the cells of the centre itself. 

 Such a conclusion brings under one head all the several factors which we know to act 

 upon the respiratory centre, namely, tension of carbon dioxide, presence of acids in the 

 blood especially lactic and considerable diminution of oxygen supply to the cells. 

 The respiratory centre would then not differ qualitatively from any other part of the 

 central nervous system. Its special function would be determined simply by the evolution 

 to a marked degree of a sensibility to hydrogen ions which is already possessed by the whole 

 of the central nervous system and indeed by practically every tissue of the body. 



We may conclude that mere lack of oxygen is not to be regarded in 

 itself as an excitatory agent. Its influence will be rather to paralyse all 



