1212 PHYSIOLOGY 



contraction of the pupil, and a discharge along the whole sympathetic 

 system, producing the various phenomena of vaso-constriction, 

 erection of hairs, sweating, salivation, which are generally brought 

 about by stimulation of different parts of this system. The phenomena 

 of the third stage are due to exhaustion of the nerve-centres, accom- 

 panied or preceded by exhaustion and dilatation of the heart, the 

 circulation failing before the excitation of the lower centres has 

 entirely come to an end. In this third stage it is impossible by the 

 strongest stimuli to evoke any reflex. 



Considerable discussion has taken place as to the exact nature of the stimu- 

 lation brought about by want of oxygen. The blood of animals which have been 

 killed by asphyxia is known to contain reducing substances, so that oxygen 

 added to it disappears and cannot be recovered in a vacuum. Pfliiger therefore 

 suggested that it was these reducing substances themselves which were effective 

 exciting agents. It was shown many years ago by Hoppe-Seyler and his pupils 

 that in conditions of chronic oxygen 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 hyperpncea and convulsions 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 hyperpncea 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 produced in the blood. If therefore 

 we ascribe the hyperpncea to the production of lactic acid 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. 



f In dealing with the question of the blood alkalinity we defined neutrality 

 as a condition in which there was equivalent concentration of H and OH ions. 

 In the blood the H ion concentration is about 0-3 x 10~ 7 N. The alkalinity 



concentration OH ions 



is expressed bv ; -: ^. . The acids and bases of the blood-serum 



concentration H ions 



and of the tissue-fluids generally are in such proportions as to maintain the 

 approximate neutrality of these fluids even after considerable additions of acid 

 or alkali. Thus 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 produced 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 electrically the change in 

 hydrogen ion concentration caused by the change from arterial to venous 



