368 EXAMPLES OF CHEMICAL CORRELATION 



repeated and forced filling and emptying of the lungs by an indifferent 

 gas, such as hydrogen or nitrogen, and when this has been done, it is 

 found that the carbon-dioxide tension, in the alveolar air and therefore 

 in the arterial blood, is decidedly lower than normal. 



The increased carbon-dioxide tension of the blood in obstructed 

 breathing is therefore the stimulus which excites the activity of the 

 respiratory center. But the carbon dioxide may conceivably act in 

 either of two ways upon the center, namely as a specific chemical stimu- 

 lant, or else indirectly by the increase in the hydrogen ion concentra- 

 tion of the blood which it brings about. 



The experiments of Winterstein were designed to elucidate this 

 question. This investigator introduced acids into the blood which was 

 passing by the carotid artery to the brain, and he obtained a decided 

 acceleration of the respiratory rhythm as a result. Prior to these 

 experiments of Winterstein, it had also been shown that in frogs in 

 which the floor of the fourth ventricle has been exposed, the direct 

 application of acids to this area of the medulla causes acceleration of the 

 respiratory rhythm, while that of alkalies slows it. Both experiments 

 were inconclusive, however, because they did not enable us to ascer- 

 tain whether the acids administered excited the center by virtue of the 

 hydrogen ions which they contributed to the blood, or by setting free 

 carbon dioxide from bicarbonates and thus increasing the carbon- 

 dioxide tension of the blood. Subsequent experiments by Laqueur 

 and Verzar threw more light upon the question, tending to show that 

 carbon dioxide is a specific stimulant for the respiratory center, for they 

 found, using Winterstein's technique, that the nature of the acid 

 added to the cerebral circulation profoundly affected the result, and 

 the efficiency of the various acids did not run parallel to their "strength" 

 or dissociation into ions. Carbon dioxide, lactic acid and various fatty 

 acids are much more efficient stimulators of respiration than the 

 strong mineral acids. Evidently, therefore, we have here to deal with 

 an effect which is not wholly a hydrogen-ion effect, but also in part 

 an effect involving the undissociated molecule or the anions of the 

 acid employed* 



THE CHEMICAL REGULATION OF THE CIRCULATORY SYSTEM. 



Removal of the Suprarenal Glands in animals, or their destruction by 

 disease (usually tubercular) in man, is followed by the rapid appearance 

 of intense prostration and muscular weakness. The blood-pressure 

 falls to an extremely low level, and death finally supervenes. In man, 

 the destruction of the glands by disease is usually somewhat gradual 

 and the symptoms are correspondingly slow to develop. They are of 

 the same description as those which develop in animals when these 

 glands are excised, but, in addition, a peculiar patchy bronze-like pig- 

 mentation of the skin occurs. The nature of the pigment which is 

 deposited in these patches is unknown, but it is highly probable that 



