in the general circulation the oxygen gradually disappears, and is replaced, in the venous blood, by carbonic acid. The oxygen which thus disappears from the blood in the general circulation does not, for the most part, enter into direct combination in the blood itself. On the contrary, it exists there, as we have already stated, in the form of a simple solution. It is absorbed, however, from the blood of the capillary vessels, and becomes fixed in the substance of the vascular tissues. The blood may be regarded, therefore, in this respect, as a circulating fluid, destined to transport oxygen from the lungs to the tissues; for it is the tissues themselves which finally appropriate the oxygen, and fix it in their substance.

The next important question which presents itself in the study of the respiratory process relates to the origin of the carbonic acid in the venous blood. It was formerly supposed, when Lavoisier first discovered the changes produced in the air by respiration, that the production of the carbonic acid could be accounted for in a very simple manner. It was thought to be produced in the lungs by a direct union of the inspired oxygen with the carbon of the blood in the pulmonary vessels. It was found afterward, however, that this could not be the case; since carbonic acid exists already formed in the blood, previous to its entrance into the lungs. It was then imagined that the oxidation of carbon, and the consequent production of carbonic acid, took place in the capillaries of the general circulation, since it could not be shown to take place in the lungs, nor between the lungs and the capillaries. The truth is, however, that no direct evidence exists of such a direct oxidation taking place anywhere. The formation of carbonic acid, as it is now understood, takes place in three different modes: 1st, in the lungs; 2d, in the blood; and 3d, in the tissues.

First, in the lungs. There exists in the pulmonary tissue a peculiar acid substance first described by Verdeil' under the name of "pneumic" or "pulmonic" acid. It is a crystallizable body, soluble in water, which is produced in the substance of the pulmonary tissue by transformation of some of its other ingredients, in the same manner as sugar is produced in the tissue of the liver. It is on account of the presence of this substance that the fresh tissue of the lung has usually an acid reaction to test-paper, and that it has also the property, which has been noticed by several observers, of

decomposing the metallic cyanides, with the production of hydrocyanic acid; a property not possessed by sections of areolar tissue, the internal surface of the skin, &c. &c. When the blood, therefore, comes in contact with the pulmonary tissue, which is permeated everywhere by pneumic acid in a soluble form, its alkaline carbonates and bicarbonates, if any be present, are decomposed with the production on the one hand of the pneumates of soda and potass, and on the other of free carbonic acid, which is exhaled. M. Bernard has found' that if a solution of bicarbonate of soda be rapidly injected into the jugular vein of a rabbit, it becomes decomposed in the lungs with so rapid a development of carbonic acid, that the gas accumulates in the pulmonary tissue, and even in the pulmonary vessels and the cavities of the heart, to such an extent as to cause immediate death by stoppage of the circulation. In the normal condition, however, the carbonates and bicarbonates of the blood arrive so slowly at the lungs that as fast as they are decomposed there, the carbonic acid is readily exhaled by expiration, and produces no deleterious effect on the circulation.

Secondly, in the blood. There is little doubt, although the fact has not been directly proved, that some of the oxygen definitely disappears, and some of the carbonic acid is also formed, in the substance of the blood-globules during their circulation. Since these globules are anatomical elements, and since they undoubtedly go through with nutritive processes analogous to those which take place in the elements of the solid tissues, there is no reason for disbelieving that they also require oxygen for their support, and that they produce carbonic acid as one of the results of their interstitial decomposition. While the oxygen and carbonic acid, therefore, contained in the globules, are for the most part transported by these bodies from the lungs to the tissues, and from the tissues back again to the lungs, they probably take part, also, to a certain extent, in the nutrition of the blood-globules themselves.

Thirdly, in the tissues. This is by far the most important source of the carbonic acid in the blood. From the experiments of Spallanzani, W. Edwards, Marchand and others, the following very important fact has been established, viz., that every organized tissue and even every organic substance, when in a recent condition, has the power of absorbing oxygen and of exhaling carbonic acid. G. Liebig, for example, found that frog's muscles, recently prepared and com

Archives Gén. de Méd., xvi. 222. 2 In Lehmann, op. cit., vol. ii. p. 474.

pletely freed from blood, continued to absorb oxygen and discharge carbonic acid. Similar experiments with other tissues have led to a similar result. The interchange of gases, therefore, in the process of respiration, takes place mostly in the tissues themselves. It is in their substance that the oxygen becomes fixed and assimilated, and that the carbonic acid takes its origin. As the blood in the lungs gives up its carbonic acid to the air, and absorbs oxygen from it, so in the general circulation it gives up its oxygen to the tissues, and absorbs from them carbonic acid.

We come lastly to examine the exact mode by which the carbonic acid originates in the animal tissues. Investigation shows that even here it is not produced by a process of oxidation, or direct union of oxygen with the carbon of the tissues, but in some other and more indirect mode. This is proved by the fact that animals and fresh animal tissues will continue to exhale carbonic acid in an atmosphere of hydrogen or of nitrogen, or even when placed in a vacuum. Marchand found' that frogs would live for from half an hour to an hour in pure hydrogen gas; and that during this time they exhaled even more carbonic acid than in atmospheric air, owing probably to the superior displacing power of hydrogen for carbonic acid. For while 15,500 grains' weight of frogs exhaled about 1.13 grain of carbonic acid per hour in atmospheric air, they exhaled during the same time in pure hydrogen as much as 4.07 grains. The same observer found that frogs would recover on the admission of air after remaining for nearly half an hour in a nearly complete vacuum; and that if they were killed by total abstraction of the air, 15,500 grains weight of the animals were found to have eliminated 9.3 grains of carbonic acid. The exhalation of carbonic acid by the tissues does not, therefore, depend directly upon the access of free oxygen. It cannot go on, it is true, for an indefinite time, any more than the other vital processes, without the presence of oxygen. But it may continue long enough to show that the carbonic acid exhaled is not a direct product of oxidation, but that it originates, on the contrary, in all probability, by a decomposi tion of the organic ingredients of the tissues, resulting in the production of carbonic acid on the one hand, and of various other substances on the other, with which we are not yet fully acquainted; in very much the same manner as the decomposition of sugar during fermentation gives rise to alcohol on the one hand and to

Lehmann, op. cit., vol. ii. p. 442.

carbonic acid on the other. The fermentation of sugar, when it has once commenced, does not require the continued access of air. It will go on in an atmosphere of hydrogen, or even when confined in a close vessel over mercury; since its carbonic acid is not produced by direct oxidation, but by a decomposition of the sugar already present. For the same reason, carbonic acid will continue to be exhaled by living or recently dead animal tissues, even in an atmosphere of hydrogen, or in a vacuum.

Carbonic acid makes its appearance, accordingly, in the tissues, as one product of their decomposition in the nutritive process. From them it is taken up by the blood, either in simple solution or in loose combination as a bicarbonate, transported by the circulation to the lungs, and finally exhaled from the pulmonary mucous membrane in a gaseous form.

The carbonic acid exhaled from the lungs should accordingly be studied by itself as one of the products of the animal organism, and its quantity ascertained in the different physiological conditions of the body. According to the researches of Vierordt,' which are regarded as the most accurate on this subject, an adult man gives off 1.62 cubic inch of carbonic acid with each normal expiration. This would give 19.16 cubic inches per minute, 1149.6 cubic inches per hour, and 15.4 cubic feet per day. The amount of carbonic acid exhaled, however, varies from time to time, according to many different circumstances; so that no such estimate can represent correctly its quantity at all times. These variations have been very fully investigated by Andral and Gavarret, who found that the principal conditions modifying the amount of this gas produced were age, sex, constitution and development. The variations were very marked in different individuals, notwithstanding that the experiments were made at the same period of the day, and with the subject as nearly as possible in the same condition. Thus they found that the quantity of carbonic acid exhaled per hour in five different individuals was as follows:

QUANTITY OF CARBONIC ACID PER HOUR.

2

In Lehmann, op. cit., vol. ii. p. 439.

2 Annales de Chimie et de Pharmacie, 1843, vol. viii. p. 129.

With regard to the difference produced by age, it was found that from the period of eight years up to puberty the quantity of carbonic acid increases constantly with the age. Thus a boy of eight years exhales, on the average, 564 cubic inches per hour; while a boy of fifteen years exhales 981 cubic inches in the same time. Boys exhale during this period more carbonic acid than girls of the same age. In males this augmentation of the quantity of carbonic acid continues till the twenty-fifth or thirtieth year, when it reaches, on the average, 1398 cubic inches per hour. Its quantity then remains stationary for ten or fifteen years; then diminishes slightly from the fortieth to the sixtieth year; and after sixty years diminishes in a marked degree, so that it may fall so low as 1038 cubic inches. In one superannuated person, 102 years of age, Andral and Gavarret found the hourly quantity of carbonic acid to be only 665 cubic inches.

In women, the increase of carbonic acid ceases at the period of puberty; and its production then remains constant until the cessation of menstruation, about the fortieth or forty-fifth year. At that time it increases again until after fifty years, when it subsequently diminishes with the approach of old age, as in men. Pregnancy, occurring at any time in the above period, immediately produces a temporary increase in the quantity of carbonic acid.

The strength of the constitution, and more particularly the development of the muscular system, was found to have a very great influence in this respect; increasing the quantity of carbonic acid very much, in proportion to the weight of the individual. The largest production of carbonic acid observed was in a young man, 26 years of age, whose frame presented a remarkably vigorous and athletic development, and who exhaled 1591 cubic inches per hour. This large quantity of carbonic acid, moreover, in well developed persons, is not owing simply to the size of the entire body, but particularly to the development of the muscular system, since an unusually large skeleton, or an abundant deposit of adipose tissue, is not accompanied by any such increase of the carbonic acid.

Andral and Gavarret finally sum up the results of their investigations as follows:

1. The quantity of carbonic acid exhaled from the lungs in a given time varies with the age, the sex, and the constitution of the subject.

2. In the male, as well as in the female, the quantity of carbonic