The chemical regulation of respiration was first clearly set forth by Haldane and Priestly, the demonstration of it following immediately on their discovery of a satisfactory method of deter mining the composition of alveolar air. The essential point emerged that at various altitudes which ranged between that of the top of Ben Nevis and the bottom of the Dolcoath mine, al though the percentage of carbon dioxide in the alveolar air alters, the percentage becoming lower as the barometric pressure in creases, the actual partial pressure of carbon dioxide in the alveoli and hence the concentration of that gas in the blood remains at such altitudes almost unchanged. This constancy of the pressure of carbon dioxide in the alveolar air means that the greater the barometric pressure the more the carbon dioxide produced by the body is diluted in the lung. As the carbon dioxide produced by the body is approximately constant in amount, the total ventila tion of the lung, and hence the respiratory efforts must be greater the higher the barometer and the lower the altitude. Any effort to increase the carbon dioxide pressure in the blood, as by inhal ing carbon dioxide or shedding it into the blood as the result of muscular exercise, has the effect of stimulating the respiratory centre and increasing the respiratory efforts more especially as regards the depth of respiration.
Controversy has ranged round the question of whether carbon dioxide is a specific stimulus to the respiratory centre, or whether its presence in the blood acts indirectly and, by increasing the concentration of hydrogen ions, stimulates the centre; the hydro gen ions and not the carbon dioxide acting as the stimulus. In favour of the latter view is the fact that after violent exercise, when the hydrogen ion concentration of the blood is increased and concentration of carbon dioxide diminished (lactic acid being present in considerable quantities), breathing may still be very laboured. It is certain also that, as shown by Winterstein, the administration of other acids to animals will cause dyspnoea (laboured breathing). On the other hand, other acids do not pro duce at all so striking an effect as carbon dioxide.
It is probable that CO2 does act not specifically but by virtue of its power of increasing the hydrogen ion concentration in the brain; and that its potency in this respect is due to the ease with which it diffuses from the blood into the tissue of the brain itself. It is ultimately the hydrogen ion concentration inside the nerve cells which constitute the respiratory centre which would affect their stimulation—a fact which has been stressed by Gesell. According to his conception, if the activity of the respiratory centre is heightened as the result of nervous impulses playing upon it, the cells themselves will work harder, produce more CO2 and undergo a sort of secondary stimulation. In the language of
wireless, the original nervous stimulus will be "amplified." Sim ilarly, if the carbon dioxide in the blood be increased, that pro duced by the cells will be unable to escape and will stimulate the centre.
In the above description it has been assumed that the irritabil ity of the cells, i.e., the degree of response which any particular stimulus will provoke, remains constant. This is not so in all circumstances. Many drugs, such as morphia, depress the centre, but the most interesting case of altered irritability of the centre is that of oxygen want (see ANOXAEMIA). If the respiratory centre be insufficiently supplied with oxygen over considerable periods of time the irritability is heightened, a given amount of exercise will then produce a much greater degree of breathless ness than it evokes in normal circumstances.
Temperature has an important effect upon respiration. This is less marked in man than in animals, which do not sweat; if the dog or goat, for instance, lies in the sun, shortly the respira tion will become very rapid and shallow, a great volume of air will pass in and out of its respiratory passages, but the amount of air which ventilates the alveoli is not correspondingly increased. This alteration in the type of respiration (tachypnoea) may, in part, be due to rise in the temperature of the blood. If this blood, as it passes through the carotid artery to the brain be warmed, tachypnoea results. But tachypnoea is probably also helped by a reflex nervous mechanism initiated by the actual heating of the skin, for it is claimed that the temperature of the blood may even be lowered. The purpose is clear. The heat loss is, of course, proportional to the amount of aqueous vapour which leaves the body, and the aqueous vapour in its turn is roughly proportional to the total ventilation. Therefore, by establishing a large total ventilation the body temperature is kept from rising, but if there were also a large alveolar ventilation the loss of carbon dioxide would be too great, the respiration being, however, shallow the alveolar ventilation is not greatly increased.