increasing the richness of the blood in hæmoglobin; this may be done by transfusing more blood into the vessels.

The researches of L. Brasse relate chiefly to the influence of temperature on the dissociation of oxyhæmoglobin. He finds that the tension of dissociation for oxyhæmoglobin at 0° C. is nil. The compound is thus a stable one at that temperature; in hibernating animals, the temperature of the body is very low, and the blood is red in the veins as well as in the arteries. The tension of dissociation increases with the temperature, and a mammal dies when the temperature of its blood reaches 45° C. At this temperature, although the tension of dissociation is still lower than the partial pressure of the atmospheric oxygen, it is higher than that of the oxygen in the pulmonary alveoli. In birds, on the other hand, where by the arrangement of air sacs the aëration of the blood is very complete, they do not die until their blood reaches the temperature of 50° C.

The tension of the gases is thus the sum of the tension of dissociation of the oxyhæmoglobin, bicarbonates, and similar compounds, with the physical tension of the small amount of the gases dissolved in the blood plasma. The tension (composed of these two factors) of the gases in the blood is not nearly so great as it would be if all the gas in the blood were in a free or uncombined condition. The measurement of the tension of the gases in the blood was carried out by Pflüger, and his pupils Wolffberg,2 Strassburg, and Nussbaum; the instrument they used is called an aërotonometer."

3

The average results obtained may be thus summarised (Strassburg):

=

Tension of oxygen in arterial blood 29.64 mm. of mercury=39 per cent. of an atmosphere.

Tension of oxygen in venous blood=2204 mm. of mercury=2·9 per cent. of an atmosphere.

1 Pflüger's Archiv, vi. 43.

3 Ibid. vi. 65.

2 Ibid. iv. 465; vi. 23.
4 Ibid. vii. 296.

5 The use of this instrument may be best explained by an example. Suppose that one wished to ascertain the tension of carbonic acid in the blood; the blood direct from the living vessels is introduced into the upper end of a vertical glass tube (kept at a constant temperature by a jacket of water) containing nitrogen and a small known per centage of carbonic acid. The blood runs down the tube and is at once removed at the lower end, means being provided to prevent air getting to it. If the tension of carbonic acid in the blood is greater than in the mixture in the tube, then the amount of carbonic acid in the tube will be increased after the blood has passed through it; if the tension in the blood is less, then the amount of carbonic acid in the tube will be found to be diminished. By successive experiments it is found that for a certain percentage the amount of carbonic acid undergoes no change; this percentage therefore exerts the same tension as the carbonic acid in the blood. Strassburg (loc. cit.) gives a figure of the

aerotonometer.

Tension of carbonic acid in arterial blood=21.28 mm.

=2.8 per cent. of an atmosphere.

of mercury

Tension of carbonic acid in venous blood=41.04 mm. of mercury =54 per cent. of an atmosphere.1

The differences in the tension of the gases is thus much less than the differences in their volume, in the two varieties of blood.

Let us now compare the tension of the blood gases with the partial pressure of the gases in the pulmonary alveoli. Wolffberg obtained the residual or alveolar air from the lungs of dogs by catheterisation, and the following are his mean results :

Tension of oxygen in alveolar air=27·44 mm. of mercury=3.6 per cent. of an atmosphere.

Tension of carbonic acid in alveolar air=27·06 mm. of mercury== 3.56 per cent. of an atmosphere.2

Now if the line AB in the accompanying diagram represents the alveolar membrane, there is the alveolar air on one side of it, and venous blood on the other; the tension of the two gases in each is represented in the diagram, and the direction in which diffusion takes place is shown by the arrows; the oxygen passing from alveolar air into the blood, the carbonic acid in the reverse direction.

It has long been felt that the comparatively small differences of partial pressure (particularly of oxygen) do not completely explain the very great differences in the volume of the gases in arterial and venous blood, and any account of the gases of the blood would be incomplete without a reference to the ingenious theory recently advanced by Ernst Fleischl v. Marxow. The author, after stating the usual theory of respiration and its difficulties, asks how it is that, if the tissues have a greater affinity for oxygen than hæmoglobin, the blood of animals killed by asphyxia still contains a considerable amount of oxyhæmoglobin; and v. Marxow believes that in the sharp, sudden stroke of the heart's beat he has discovered a physical agency which assists in the work of dissociation; according to him the blood is kept in motion by a series of quick sudden strokes, because for the taking up of the oxygen by the tissues, and the elimination of carbonic acid by the lungs, it is not sufficient that the blood runs steadily through the systemic and pulmonary capillaries respectively; and therefore a short, hard

1 This rose on the coagulation of the blood to 61.79 mm. Hg, -813 per cent. of an atmosphere. 2 Nussbaum obtained rather a higher number, 29:18 mm. Hg. 3 Die Bedeutung des Herzschlages für d. Athmung; eine neue Theorie der Respiration, Vienna. I am indebted to Prof. McKendrick's address to the Brit. Med. Assoc. 1888 (Brit. Med. Journ. August, 1888) for the above abstract of v. Marxow's theory.

stroke is given to it immediately before it enters, and immediately after it has left the lungs; the systole of the left ventricle assisting in the liberation of the oxygen; of the right ventricle in the liberation of the carbonic acid. That a blow has very considerable power in assisting the liberation of gases can be readily demonstrated with an ordinary hypodermic syringe; if the piston be pulled up, and water allowed to rush into the vacuum so formed, bubbles of gas will come off from the water; but if the handle of the piston first receives a sharp blow from a mallet, the gas bubbles will come off so rapidly that the water froths.

Although physiologists cannot but treat with the greatest respect the conclusions arrived at by so eminent a physicist as Fleischl von Marxow, it must be admitted that there are many difficulties in the way of fully accepting his theory in its entirety. These difficulties are chiefly the two following:

(1) In small mammals the stroke of the heart cannot be nearly so powerful as in large mammals; but still the same respiratory exchanges go on.

(2) In cold-blooded animals there is only one ventricle, and the blood receives only a single blow; but, nevertheless, on its way from the heart back to the heart again it undergoes two gaseous exchanges, first in the lungs or gills, secondly in the tissues.

In spite of these obvious objections, which show that v. Marxow is inclined to

exaggerate the importance of the heart beat, it is, however, quite possible that in the warm-blooded animals, where the gasecus exchanges are more extensive than in the cold-blooded animals, the force of the blow given to the blood by the heart may exercise some auxiliary impulse in the liberation of the blood gases.

Another attempt to elucidate the perplexing questions involved in the respiratory exchange of gases has been recently made by Christian Bohr. We have already seen that some of the carbonic acid is contained in the red corpuscles, and Bohr considers that it is in actual combination with the hæmoglobin; he considers that this union is like oxyhæmoglobin-a dissociable one-and that dissociation takes place in the pulmonary alveoli. If this is really the case, hæmoglobin appears to be not only an oxygen carrier but also a carbonic acid carrier. We have, of course, in addition to this, the carbonic acid dissolved in the plasma, in the form of carbonates and bicarbonates. Bohr's theory of the combination which occurs in the red corpuscles appears to me so important and full of interest that I propose here to give a brief résumé of his paper :

Setschenow, and later Zuntz, stated that a solution of hæmoglobin at the atmospheric pressure absorbs more carbonic acid than the same volume of water. Bohr's research was devoted to studying this subject more fully, and to ascertaining the relation between the tension of the carbonic acid and the amount absorbed per gramme of hæmoglobin. A special absorptiometric method employed was described by him in an earlier paper. Pure solutions of crystalline hæmoglobin from the dog, and pure carbonic acid, were employed; these were brought

in contact with one another, the gas being at a known pressure, and the temperature kept constant throughout. The amount of gas absorbed was afterwards pumped off and estimated. Some preliminary experiments were made with water; the result of one of these, in which 41 grammes of water were used, may be represented graphically as in tig. 66. The line which indicates the increase of absorption is constructed from ordinates representing the amount of absorbed gas in grammes, the abscissæ the pressure of the gas in mm. of mercury. As is seen, the result is a straight line, the weight of gas absorbed being proportional to its tension (Dalton-Henry law).

Experiments were then made with hæmoglobin solutions; the following table represents a portion of one of these :

The quantity of carbonic acid absorbed by hæmoglobin is thus immensely greater than that explicable on simply physical grounds. The curves in fig. 67

1 Mém. de l'acad. de St. Pétersbourg, vol. xxvi. 1879.

3

Hermann's Handbuch, vol. iv. 2. p. 76.

Bohr, Exper. Untersuch. u. d. Sauerstoffsaufnahme des Blutfarbstoffs, Kopenhagen, 1885.

represent graphically two experiments; the abscissæ represent as before the pressure, the ordinates the quantity of gas absorbed per gramme of hæmoglobin. The curve is very different from the straight line of fig. 66, and the ascent of the curve is especially steep at the lower pressures. The upper curve is the representation of an experiment performed with a less concentrated solution of hæmoglobin than in the experiment represented by the lower curve. It thus appears that the amount of gas absorbed is less in the more concentrated solution. Contrasting the curves with those obtained in experiments with other gases (oxygen, carbonic oxide, nitric oxide) which are known to form compounds with hæmoglobin, they are found to be different. Hence, if we have to do with a chemical union of carbonic acid and hæmoglobin, the gas is combined differently from that in oxyhæmoglobin, CO-hæmoglobin, and NO-hæmoglobin respectively. The spectrum of CO, hæmoglobin has still to be investigated. S. Jolin repeated these experiments with guinea-pig's hæmoglobin, and obtained similar results. With birds' hæmoglobin the curves were rather different, both in respect to oxygen and carbonic acid.

TISSUE RESPIRATION

Our present knowledge concerning tissue respiration has been necessarily dealt with in our consideration of the gases of the blood. It will be, however, here interesting to add a few historical points in connection with this subject.3

According to Lavoisier, respiration was considered to be a slow combustion of carbon and hydrogen; the air supplied the oxygen, the blood the combustible materials. The great French chemist's opinions were however much misunderstood, and a notion prevailed that, according to him, combustion occurred only in the lungs; that these organs in fact acted as a stove for the remainder of the body. Lagrange a few years later (1791) clearly pointed out how impossible this was, for if all the heat of the body were produced in the lungs alone, their temperature would be raised so high as to destroy them; he therefore Supposed with Lavoisier that the oxygen dissolved in the blood combined there with carbon and hydrogen to form carbonic acid and water respectively.

The next step was the discovery by Spallanzani that animals confined in an atmosphere of nitrogen or of hydrogen exhaled carbonic acid to almost as great an extent as if they had breathed air; he supposed that the carbonic acid was formed by digestion in the stomach, then passed through the tissues, and was finally exhaled. He thus missed a great step in the discovery, namely, that the carbonic acid is pro

'S. Torup (Maly's Jahresb. xvii. 115) states that the band of CO. hæmoglobin is almost indistinguishable from that of hæmoglobin, but careful measurements show that its darkest part is rather nearer the violet end of the spectrum in the former than in the latter. This observation, however, still awaits confirmation.

2 Du Bois Reymond's Archiv, 1889, p. 265.

3 For these I am indebted to Dr. McKendrick's address already quoted.