Other forms of activity.-Not only does muscular work increase the amount of gaseous interchange, but all forms of protoplasmic activity act similarly; chemical decompositions are most rapid and extensive when an organ is active. Among forms of activity, secretion is the most important after muscular contraction.

Number and Depth of Respirations.-The most marked effect of increasing the respiratory movements is not to influence the amount of carbonic acid formed in the body, but to accelerate the removal of that which has been already formed.

An increase in the number of respirations (the depth remaining the same), or an increase in their depth (the number remaining the same), causes an increase in the amount of carbonic acid given off, though with reference to the total amount of gases exchanged it is relatively diminished. This may be illustrated by the following table from Vierordt :

Corroborative results have been obtained by Voit and Lossen,' Speck, Berg," and Becher.1

Deficiency of Air or of Oxygen. Dyspnea. Asphyxia—When a due supply of air is not obtained the oxygen in the arterial blood sinks below the normal, the blood pressure rises, and the respiratory movements become deeper (dyspnoea or hyperpnoea); these movements increase until they pass to other muscles, and so a condition of general convulsions sets in; this is followed by exhaustion and death; the train of symptoms constituting what is known as asphyxia.

An increased supply of Air or Oxygen. Apnea.-After several inspiratory efforts of great force it is easy to hold the breath for a longer time than usual. If air be rapidly pumped into the lungs of one of the lower animals there is no effort made to breathe for the space of some seconds or even minutes. The usual explanation given of these phenomena is as follows: the respiratory centre in the medulla is largely influenced by the quality of the blood sent to it. In ordinary respiration, the normal blood not being fully oxygenated stimulates it to send out impulses which result in the normal respiratory efforts: too great an amount of carbonic acid in the blood excites it to increased activity (dyspnoea); too large a supply of oxygen inhibits its activity altogether (apnoea). This view of the cause of the respiratory movements is, however, not universally accepted. Thus Hoppe-Seyler' states that normal arterial blood contains no such reducing substances as have been considered stimulants of the respiratory centre. He is inclined to believe that the excitation to respiratory activity is to be found in the changes that occur in the lungs; these stimulate the terminations of the sensory

1 Zeit. Biol. ii. 244.

2 Schriften d. Gesellsch. z. Forder. d. Ges. Naturwiss. Marburg, x. 3.

3 Deutsch. Arch. klin. Med. vi. 291.

4 Die Kohlensäurespannung im Blut, Zürich, 1855.

5 Physiol. Chem. p. 544.

nerves in the lungs, and by means of reflex action the muscular movements of the respiratory muscles are brought about. Max Marekwald' also adduces many weighty arguments against the generally received theory of respiration. Dyspnoea seems to be undoubtedly caused by excess of carbonic acid in the blood, whether this affects the nerve centre or the nerve terminations. But apnoea, according to Hoppe-Seyler, is not caused by excess of oxygen in the blood, as normal arterial blood is already completely or almost completely saturated with oxygen; from the study of his own experiments and those of other investigators,3 he concludes that it is simply due to fatigue of the respiratory apparatus.

Poisonous Gases.-Excess of carbonic acid produces feelings of discomfort (headache, &c.); if the excess is very great there is laboured breathing, and ultimately a state of narcosis without convulsions, in which the animal dies. Carbonic oxide is even more deleterious; it combines with the hæmoglobin, and so prevents the blood, and thus the tissues, from being properly oxygenated (see p. 281).

Sulphuretted hydrogen acting as a reducing agent produces similar effects. Some gases, like chlorine, ammonia, nitrous acid, &c., are irrespirable, producing spasm of the glottis. Nitrous oxide causes narcosis, and is largely used as an anesthetic.

Ozone, instead of making the blood more arterial, causes it to assume venous characters in all the vessels; this is perhaps explained by its greater density, interfering with the due excretion of carbonic acid from the blood; it also causes local irritation of the respiratory passages; it slows both heart and respiration (Dewar and McKendrick, J. Barlow, Filipow"). Hydrogen and marsh gas, if mixed with a sufficient quantity of oxygen, have no effect on respiration.

The poisonous effects of respired air.- Dr. B. W. Richardson' has made experiments on animals in order to investigate the effect of air that has been breathed previously by other animals. He finds that after air or oxygen has been once used it is very poisonous, even though all carbonic acid, ammonia, and all appreciable impurities have been removed. He therefore infers that something is removed from the oxygen by the process of respiration; and that this 'devitalised oxygen' can be revitalised by electrical brush discharges from the positive pole of a frictional machine.

As long as oxygen is regarded as an element, it is impossible to accept this explanation. A much more probable explanation is that some impurity is added to the oxygen during the process of respiration, and that this impurity is the poison. What, then, is this impurity? Jackson" considers it may be carbonic monoxide. What seems to be certain is that it is not carbonic dioxide; a large admixture of pure carbonic acid in the air will not produce the symptoms of poisoning. Men can breathe for two to three hours without marked discomfort air which contains as much as 20 per cent. of carbonic acid. Brown-Séquard and d'Arsonval speak of the poison vaguely as a pulmonary poison, and consider it

1 Innervation of Respiration, translated by T. A. Haig: Blackie and Son, 1888; Zeit. Biol. xxvi. 259. See also H. Head, Journ. of Physiol. x. 1.

? Physiol. Chem. p. 519.

3 Rosenthal, Arch. d. Anat. u. Physiol. 1864, p. 456; 1865, p. 191. Pflüger, Pflüger's Archiv, i. 90. A. Ewald, Ibid. vii. 575; also 'Ueber die Apnoë,' Diss. Bonn, 1873.

4 Proc. Roy. Soc. 1873-4.

6 Pflüger's Archiv, xxxiv. 335.

5 Journ. Anat. Oct. 1879.

Brit. Med. Journal, vol. ii. 1860.

Chem. News, lv. 253.

*

9 Comptes rend. 1887, 1888, 1889.

Proc. Physiol. Soc. 1887, p. 31.

may be alkaloidal, and that it passes into the expired air from the lungs; this poison, whatever it is, can be removed by passing the air containing it through tubes containing beads moistened with sulphuric acid.

Although the mere presence of 1 per cent. of pure carbonic acid in the air has little or no effect, an atmosphere in which the carbonic acid has been raised to this proportion by respiration is highly detrimental; indeed, air rendered so impure by respiration as to contain even 008 per cent. of carbonic acid is very unwholesome. In an hour a man will add about 1 per cent. of the gas to about 70 cubic feet of air; and if the proportion is kept down to 0.1 per cent., at least 700 cubic feet should be supplied to him every hour, or about 16,800 cubic feet in the 24 hours.

Changes in atmospheric pressure.'--Gradual diminution of pressure produce symptoms of asphyxia; convulsions, however, are not invariable. A sudden and great diminution of pressure may produce death by the liberation of nitrogen within the blood vessels, and a consequent mechanical interference with the circulation. Increase of pressure up to that of several atmospheres produces symptoms of narcotic poisoning; at a pressure of 20 atmospheres the animals die of asphyxia, as when oxygen is deficient. The oxidations in the body are at this pressure diminished. Plants, bacteria, &c., are similarly killed by too great pressure of oxygen; and at a high pressure of oxygen even phosphorus will not burn.

It is, however, only very great extremes of pressure that affect animals injuriously. As is explained more fully in connection with the subject of the blood gases, very considerable variations of pressure may take place, especially if gradual, and without any resulting inconvenience to the animal. A mere excess of oxygen in the air breathed has no appreciable influence either on the amount of oxygen taken up or carbonic acid given out by the animal."

Marcet states that less air (reduced to 0° C. and 760 m.m.) is taken into the lungs for the formation and emission of a given weight of carbonic acid under lower than under higher atmospheric pressures.

THE GASES OF THE BLOOD

H. Davy1 was the first to observe that oxygen was evolved on heating the blood. Magnus made more accurate observations. He found that oxygen could be obtained either by passing a stream of hydrogen or carbonic acid through the blood, or by placing blood in the vacuum of an air pump, and that the quantity of oxygen obtained from arterial was greater than that from venous blood. Later Bunsen, Lothar Meyer, and later still after the invention of the mercurial air pump Hoppe-Seyler, Setschenow and Ludwig, Helmholtz, and Pflüger worked at the subject.

1 Paul Bert, Recherches exp. sur la pression barcmérique, 1874.

2 Some recent experiments on this subject by Saint-Martin will be found in the Compt. rend. xcviii. 241.

3 Phil. Trans. vol. clxxxi. (1890), p. 1.

4 Gilbert's Ann. xii. 593.

5 Poggendorff's Ann. xl. 583 (1838); lxvi. 177.

6 Bunsen, Gasometrische Methoden, Braunschweig, 1857.

7 L. Meyer, Die Gase des Blutes, Diss. Göttingen, 1857.

Zeit. rat. Med. viii. 256.

The general principles underlying the construction and use of the mercurial air pump have been described in an earlier chapter (see p. 30). It will be here unnecessary to repeat the principles on which the analysis of the gases is performed (see Chap. IV), and we can pass on

now to the results that have been obtained.

The following table' gives some numbers illustrative of the results obtained by different observers :—

Jolyet and Regnard' have made observations on the blood several aquatic animals, crustacea and fishes (see also p. 396).

Pflüger, 10 whose name is associated with the best known of the many mercurial pumps, from a large number of observations on dogs found in the arterial blood in the mean 58.3 volumes of the mixed gases per 100 vols. of blood; this was composed of 22.2 vols. oxygen (maximum 254); 343 vols. carbonic acid; and 18 vols. nitrogen.

Pflüger made, like Hirschmann, comparative observations on the gases of blood obtained from different arteries (carotid and femoral), and his results were practically the same; viz. the gases are in the two cases approximately equal, or there may be a slight loss of oxygen in the more distant artery.

During the first few minutes after blood is shed, a certain quantity of the oxygen disappears; in all probability this is stored or used up

1 Shortened from a fuller table given by Hoppe-Seyler, Physiol. Chem. p. 496.

* In all cases the volume of gas is measured at 0° C. and 760 m.m. Hg pressure.

3 Loc. cit.

Ibid. xli. 589.

4 Wien. akad. Sitzungsb. xxxvii. 293.

6 Ibid. xlv. 171.

Heidenhain, Studien d. physiol. Inst. zu Breslau, Heft ii. 1863, p. 162.

Archiv f. Anat. u. Physiol. 1866, p. 502.

9 Virchow-Hirsch. Jahresb. 1874, vol. i. p. 201. 10 Centralbl. med. Wiss. 1867, p. 724.

11 Pflüger's Archiv, i. 285.

2

by the still living corpuscles. Stroganow gives the loss of oxygen that occurs in this way as varying from 1.03 to 1.6 per cent. Schützenberger, by using indigo-white to remove the oxygen from hæmoglobin, obtained a result higher by 4-5 c.c. per 100 c.c. of blood than by the method of extracting the gas with the mercurial air pump. This difference increases with the length of time employed in the extraction of gas by the pump. Lambling 3 considers that this is in part due to the formation of a small amount of methæmoglobin. Methæmoglobin yields its oxygen to reducing agents like indigo-white, but not to the vacuum of an air pump. Hoppe-Seyler 4 states that the reduction by means of indigo-white is not trustworthy, since it is so powerful. Not only is oxyhemoglobin reduced to hæmoglobin, but the reaction goes further, so as to form hæmochromogen. Lambling, however, from numerous experiments considers that Hoppe-Seyler is at fault here; hæmoglobin is formed, and the reaction always stops short there. The question cannot, however, be regarded as settled.

The oxygen in the blood is not in a state of simple solution. According to Bunsen the absorption-coefficient of water for oxygen is 0.041; for nitrogen 0·0203 (0° C., 760 mm. Hg). If the absorption coefficient of blood were equal to that of water, the blood would be able to absorb from the air 0.86 vols. per cent. of oxygen, and 1.608 vols. of nitrogen. The absorption coefficient of blood is a little lower than that of water, and this is smaller still at the temperature of the body (37° C.) than at 0° C., the temperature for which the above numbers are calculated. With regard to the nitrogen, the quantity found in the blood is explained by simple solution. But the oxygen is far in excess of what can be accounted for in this way; the oxygen is in fact nearly all present in the form of oxyhæmoglobin; in venous blood a variable quantity of oxyhæmoglobin is found mixed with hæmoglobin. Supposing that 100 c.c. of arterial blood contain 14 grammes of oxyhæmoglobin, this would account for 23.43 vols. per cent. of oxygen; this is rather more than Pflüger actually found, but all the hæmoglobin present is rarely fully saturated with oxygen.

The blood-plasma and blood-serum contain only traces of oxygen. In dog's serum Pflüger found 0·26 vols. per cent. of oxygen, 35.26 vols. per cent. of carbonic acid, and 2·24 vols. per cent. of nitrogen.

The carbonic acid in the blood is in great part dissolved in the

1 Pflüger's Archiv, xii. 48.

17 Comptes rend. Soc. biol. (2) v. 394, 473.

2 Bull. Soc. Chim. 1873, p. 150.

4 Physiol. Chem. p. 451.

3 Bunsen defined the coefficient of absorption of a fluid for a gas as the volume of the gas (at 0° C. and 760 m.m. barometric pressure) which is taken up by one volume of the fluid.

6 Pflüger's Archiv, i. 73.