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dioxide in the serum of dog's blood was in simple solution. The result
of further experiments made ]jy Zuntz 2 upon these points is shown in
the table on p. 770.

In the next place, it is necessary to consider the amount of carbon
dioxide in loose and firm chemical combination with substances in the v
corpuscles, plasma and serum. Most of the gas is contained in the'
plasma or serum, for these fluids contain a larger quantity of carbon
dioxide than that which can be oljtained from an equal volume of blood.
The greater quantity of the gas is in a state of loose chemical combination
in the serum, for much of it can be extracted by the action of the
vacuum of a blood-pump; the remainder, however, is in firm chemical
combination, and is only set free in the pump by the addition of an
acid. In this respect a, marked contrast is observed between blood and
serum, for all the carbon dioxide can be extracted from the former by
the action of the vacuum alone, the hsemoglobin of the red corpuscles
playing, apparently, the part of an acid.'^

The following table shows the amount of carbon dioxide in loose and
firm chemical combination in serum : —



Carbon Dioxide in Serum.
(Volumes per cent.)


Carbon Dioxide in

Blood.
(Volumes per cent.)


Observer.


Extracted by
Vacuum.


In Firm Com-
bination.


Total in Com-
bination.


13-4
21-1
44-6
35-2
19-9
22-0
22-5
26-9


31-3

21-9

4-9

9-3

6-9

12-4

13-5

17-0


44-7
43-0
49-5
44-5
26-8
34-4
36-0
43-9


34-5
35-0


Schcfiffer.''

Pfiiiger.5

Zuntz. 6
J)



The differences in these results are due, as Zuntz ^ has pointed out,
to the powerful action of Piliiger's pump, and to the concentration of the
serum during its exposure to the vacuum. The carbonates of the serum give
off their gas more readily when the solution is concentrated ; this complication

^ Loc. cit., CentralN. f. d. med. JVissensch., Berlin, 1877, No. 35.

2 Hermann's "Handbuch," Bd. iv. Th. 2. S. 68.

3 Setschenow, Sitzungsh. d. k. Akad. d. TFisseiisch., y\nen, 1859, Bd. xxxvi. S. 293 ;
Pflliger, "Ueber die Kolilensaure des Blutes," Bonn, 1864, S. 5 ; Zuntz, Centralbl. J. d.
med. Wissensch., Berlin, 1867, S. 527.

^Sitzungsh. d. k. Akad. d. Ff^ismisch. Ilath.-naturiv. CL, Wien, 1860, Bd. xli. S. 616.
^ "Ueber die Kolilensaure des Blutes," Bonn, 1864, S. 11.

*^ Centralbl. f. d. med. Wissensch., Berlin, 1867, S. 529; Hermann's "Handbuch,
Bd. iv. Th. 2, S. 45.
'' Loc. cit.



/



/



7 7 2 CHEMISTR Y OF RESPIRA TION.

was avoided in the analyses made by Znntz, by the addition of distilled water
in sufficient quantity to maintain the concentration of the fluid at its original
point. Preyer ^ found that the proportion of carbon dioxide in loose and in
firm combination Avas as 2 to 3'5.

The next question to discuss is the nature of the substances with
which the carbon dioxide is combined. The facts already mentioned
show that these substances are to be sought chiefly in the serum. In
the first j)lace, analyses of the ash of serum show that the most important
constituents are the alkalies ; thus, according to Bunge's ^ experiments,
the ash from 1000 grms. of dog's serum contains 4'341 grms. sodium, of
which 3 '40 3 grms. is sufficient to saturate the chlorine. The remainder,
0"878 grms. sodium, can combine with 0'623 grms. carbon dioxide (316
c.c. at 0° and 760 mm.) to form sodium carbonate, and, in addition, with
another equal quantity to form sodium bicarbonate. Thus calculated,
a litre of plasma could hold 632 c.c. of carbon dioxide, or 63 volumes
per cent, in chemical combination. This must be considered only as an
approximate result, for the amount of sodium carbonate in serum cannot
be accurately determined by an analysis of the ash or by titration, for
the alkali is combined with other substances, especially with proteids.^

The alkalies of the blood are the most important constituents for
holding carbon dioxide in combination. Serum freed from gas can
combine with as much carbon dioxide as is necessary to form bicarbonates
with its alkalies ; any reduction in the alkalinity of the blood is accom-
panied by a decrease in carbon dioxide. Thus Walter * found only
2 to 3 volumes per cent, of carbon dioxide in the blood of rabbits poisoned
by hydrochloric acid ; Geppert and Zuntz ^ observed that the alkalinity
of the blood of rabbits was diminished by -the acid formed during tetanic
\ muscular activity, and at the same time there was a decrease in the
carbon dioxide of the blood. During diabetic coma the alkali of the blood
appears to be in great part neutralised by combination with /3-oxybutyric
acid;^ and Minkowski'' found only 3^3 volumes per cent.- of carbon
dioxide in the blood of a patient suffering from diabetic coma.

Another substance with which the carbon dioxide is supposed to
combine in serum is disodirmi hydrogen phosphate ^ (Na2HP04), with the
formation of sodium bicarbonate and sodium biphosphate. Thus —

NaoHPO, + CO2 + HoO = NaHCOs + NaH^PO^.

Sertoli^ and Mroczkowski,^^ however, found that the quantity of
phosphoric acid in the serum is so small that, if allowance be made for
that contained in lecithin and nuclein, the amount is quite insufficient

^ Sitzungsh. d. k. ATcad. d. Wissensch. Math.-naMrtv. CI., Wien, Bd. xli.x. S. 27.

" Ztschr. f. Biol., Munchen, 1876, Bd. xii. S. 204; "Lelirbuch der physiologischen
und patliologischen Chemie," Leipzig, 1889, S. 254.

2 Hoppe-Seyler, "Physiol. Chein.," Berlin, 1879, Bd. iii. S. 502; Sertoli, Med.-
cliem. Untersuch., Berlin, 1868, Heft 3, S. 350.

•* Arch. f. exper. Path. u. Pharmakol., Leipzig, Bd. A'ii.

^ Arch. f. d. ges. Physiol., Bonn, 1888, Bd. xlii. S. 189. See also this article, p. 714.

^ Stadelmann, Arch. f. ex'per. Path. u. Pharmakol., Leipzig, Bd. vii. ; Minkowski,
ibid., Bd. xviii. ; Mitth. a. d. vied. Klin, zu Konigsherg, Leipzig, 1888.

^ Loc. cit.

* Fernet, Ann. d. sc. nat., Paris, Ser. 4, tome viii. p. 160 ; Heidenhain and L. Meyer,
Stvd. d. physiol. Inst, zu Breslau, Leipzig, 1863, Heft 2 ; Ann. d. Ohem. u. Pharm.,
1862-63, vSupp. Bd. ii. S. 157.

9 Hoppe-Seyler, Mnd.-chem. Untersuch., Berlin, 1868, Heft 3, S. 350.
1" Centrulhl.f. d. med. Wissensch., Berlin, 1878. No. 20, S. 356.



CA USES OF THE EXCHANGE OF GASES. 773

to play any important part in combining with carbon dioxide. Bunge/ on
the other hand, maintains that in dog's blood the quantity of phosphoric
acid is sufficient, and that only a small quantity is combined with alkalies
in the plasma; he agrees, however, with the previous observers, that the
amount of phosphoric acid in the blood of the ox and the pig is very small.

There is also evidence to show that the proteids, especially the
globulin of serum, play some part in forming combinations with carbon
dioxide. Setschenow ^ considered that the globulin formed a combina-
tion with the carbon dioxide, whereas Sertoli held that the globulin
acted as an acid, and in the serum was combined with an alkali.

The blood corpuscles contain about one-third of the total carbon
dioxide found in the blood.^ The gas is in loose chemical combination
probably with the alkali of the phosphates, globulin, and haemoglobin
of the corpuscles, and directly with the haemoglobin. Setschenow
calculates that in 100 volumes of blood the red corpuscles contain 10
volumes, and the white corpuscles 2*5 volumes of carbon dioxide.

The experiments of Setschenow,* Zuntz,'^ Bohr,*^ and Torup'' show
that carbon dioxide combines with hgemoglobin even in the absence of an
alkali. A solution of pure crystallised hemoglobin absorbs more carbon
dioxide than does an equal volume of w^ater, and the amount of gas
absorbed is relatively large for low pressures, but relatively small for
high pressures. According to Bohr, 1 grm. of haemoglobin at 18"'4, and
under a pressure of 30 mm., combines with 2'4 c.c. of carbon dioxide ;
the pigmented portion of the hsemoglobin is supposed to combine with
oxygen and the proteid portion with carbon dioxide.

Further investigation, however, is necessary before it will be possible
with any exactitude to decide the relative importance of the different
combinations with the carbon dioxide of the blood.

The causes of the exchange of gases bet-ween the air in the
lungs and the blood. — The oxygen of the blood is derived from the air
in the alveoli of the lungs ; the carbon dioxide in the expired air comes
from the pulmonary blood, and ultimately from the tissues of the body.
The inspired air contains at 0° and 760 mm. 20-96 volumes per cent,
of oxygen, the expired air about 16 per cent., and the tissues no free
oxygen ; the carbon dioxide is 0'03 volumes per cent, in the inspired
air, about 4 in the expired air, and in the tissues is being constantly
produced. There would, therefore, appear to be sufficient causes, both
physical and chemical, to determine the passage of the oxygen inwards
and of the carbon dioxide outwards.

Oxygen, Alveolar air ^ Blood — y Tissues.

Carbon Dioxide, Tissues — -^ Blood - — ^ Alveolar air.

1 Ztsclir. f. Biol., Munchen, 1876, Bd. xii. S. 206 ; " Lehrbucli der physiologischen und
pathologischen Chemie," Leipzig, 1889, S. 256.

^ Arch. f. d. qes. Physiol., Bonn, 1874, Bd. viii. S. 1 ; Centralhl. f. d. med. Wisscnsch.,
Berlin, 1877, No. 25; 1879, No. 21; Ber. d. deutsch. chem. Gesellsch., Berlin, 1879, Bd. xii.
S. 855 ; Mem. Acad. imp. d. sc. de St. Petersbourg, 1879, tome xxvi. No. 13.

^ Alex. Schmidt, Be7\ d. k. scichs. Gesellsch. d. Wissensch. Math.-phys. CI., Leipzig,
1867, Bd. xix. S. 30; Zuntz, Centralbl.f. d. med. Wissensch., Berlin, 1867, S. 529; Her-
mann's "Handbucli," Bd. iv. Th. 2, S. 72 ; Fredericq, "Recherches sur la constitution dii
plasma sanguin," Gand, 1878, p. 49.

■* Centrcdhl. f. d. vied. Wissensch., Berlin, 1877.

5 Hermann's "Handbuch," Bd. iv. Th. 2, S. 76.

^ Beitr. z. Physiol. Carl Ludioig z. s. 70 Geburtst., Leipzig, 1887, S. 164; Jahresb.
a. d. Fortschr. d. Thier-Chem., Wiesbaden, Bd. xvii. S. 115.

'' Jahresb. il. d. Fortschr. d. Thier-Chem., Wiesbaden, Bd. xvii. S. 115.



774



CHEAIISTR Y OF RESPIRA TION.



The evidence, however, in support of this explanation must be
examined, for of late it has been challenged, especially by Bohr.^ In
the first place, it is necessary to remember that the composition of the
alveolar air is not represented by that of the air expired. The composi-
tion of the inspired and of the expired air and the tension of their
component gases can be readily determined. The tension of oxygen in
the inspired air is 159 mm., under the mean pressure of an atmosphere,
760 mm. It is difficult, however, to obtain with accuracy similar data
for the air of the alveoli. From the numerous analyses of expired air
in a man, it is possible to form only a rough estimate of the alveolar air ;
it probably contains 5 to 6 per cent, of carbon dioxide, and 14 to 15
per cent, of oxygen ; and the tension of the former would be about
36 mm., and of the latter about 114 mm. Lowy^ calculates that the
tension of oxygen in the alveoli of the human lungs is from 12-6 to 13 '5
per cent, of an atmosphere, or about 99 mm. of mercury.

In animals, direct determinations of the composition of the alveolar
air of an occluded portion of the lungs have been made. For the
collection of this air PHiiger^ constructed a special catheter (Fig. 71).

It consists of an
ordinary fine elastic
catheter, surrounded,
except at its extrem-
ities, by a tube with
a rubber enlargement
towards the free end
of the catheter. The
instrument is so small
that, when introduced
through the trachea
into a bronchus of a
dog, it causes no hind-
rance to the free
passage of air into the other parts of the lungs. The rubber enlarge-
ment is now inflated, and shuts off a portion of the lungs, from which
the alveolar air can be withdrawn thiough the inner tube of the lung
catheter. In such experiments Wolffberg * and Nussbaum ^ found
that the alveolar air of a dog contained 3 '5 per cent, of carbon dioxide,
whereas the expired air yielded 2-8 volumes per cent. It is to be noted
that this value for the alveolar air is higher than the normal, for the air
in the alveoli was shut off from the tidal air, and, in fact, represents the
air after an equilibrium had been established with the gases of the blood
passing through that portion of the lung shut off by the catheter.

In the next place, it is necessary to consider the tension of the
oxygen and carbon dioxide present in the l^lood, and this involves a
j^reliminary study of the dissociation of oxyhtemogiobin. Under the
ordinary tension of oxygen in the air, htemoglobin readily combines
with oxygen, but if the external pressure be lowered sufficiently, then
oxygen is given off, and the oxyhtemoglobin undergoes dissociation.

'^ SIcandin. Jrch. f. Physiol., Leipzig, 1891, Bd. ii. >S. 236.

- Arch. f. d. ges. Physiol., Bonn, 1894, Bd. Iviii. S. 416; "Untersuch. u. d. Respira-
tion und Circulation," 1895, S. 26.

^ Arch. f. d. ges. Physiol., Bonn, 1872, Bd. vi. S. 43.
•» Ibid., 1871, Bd. iv. S. 465 ; 1872, Bd. vi. S. 23.
5 Ibid., 1873, Bd. vii. S. 296.




Fig. 71. — Pfltiger's lung catheter.



CJ USES OF THE EXCHANGE OF GASES.



775



The force with which the oxygen sejjarates from the hteiiiogiobiii
under these circumstances is called, the tension of dissociation. The
most important researches upon this subject are those of Hlifner.^

The conditions of the dissociation of oxyhsemoglobin are the same, whether
it is a sohition of freshly-made pure crystals of haemoglobin, or fresh
defibrinated blood. The dissociation is dependent upon the concentration of the
solution of Inemoglobin ; thus, a weak solution is more readily dissociated under
a given pressure than a strong solution. It is also affected by temperature.^
As regards pressure, Hiifner found in the case of a solution containing 14 per
cent of oxyhsemoglobin at 35°, that, under a tension of oxygen of 152 mm.,
98'42 per cent, of the pigment was oxyhaemogiobin, and 1*58 per cent,
haemoglobin. When the tension of oxygen was reduced to 75 mm., the
percentages of oxyhaemoglobin and of haemoglobin were respectively 96 "89 and
3 '11, and with a lower pressure the dissociation became more rapid, as shown
by the following curves : —



wo


=ri


==i


=^


=33




^


nr?


— 1


— 1


— 1




' — 1


■ — 1


— 1


1 — y


■ — -






— 1






— 1


— 1




— 1




— 1




— 1


— 1































-—














=^







^=




~


rf:










~


\,










9^


























































\






SO




























































N
































































\
































































\
































































\\


6a






























































■1






























































'


do






























































































































/.o




























































































































'.,
































































'
































































































































;


































































JO




























































































































































































'



/60 /JO /.iO /JO



60 SO 40



Fig. 72. — Curves of dissociation of oxyhfemoglobin. The continuous line is for a
solution containing 14 per cent, of hsenioglobin, the interrupted line for a
4 per cent, solution.

It is now necessary to compare with the tension of the oxygen and
carbon dioxide in the alveolar air the tension of those gases in the blood.
For the determination of these tensions in blood Pfliiger ^ used a special
instrument, known as the aerotonometer (see Fig. 73).

The principle of the aerotonometer and of other similar instruments is this :
Blood in contact with a mixture of oxygen, nitrogen, and carbon dioxide gives
up some of its gases if their partial pressures are greater than those of the
corresponding gases in the mixture ; on the other hand, if the tensions of the
gases in the blood be lower than the respective tensions of the gases in the
mixture, the blood takes up gas. These interchanges persist until equilibrium
is estalilished, until the tension or partial pressure of the gas in the blood is

^ Ztsehr. f. 'physiol. Chem., Strassburg, Bd. vi. S. 109; Bd. xii. S. 582; Bd. xiii,
S. 28.5 ; Arch. f. Physiol... Leipzig, 1890, S. 1 ; ihicl., 1895, S. 213.
" Brasse, Comjyt. rend. Soc. cle hiol., Paris, 1888, S. 660.
^ Described by Strassburg, Arch. f. d. gcs. PhyHoL, Bonn, 1872, Bd. vi. S. 65.



776



CHEMISTR Y OF RESPIRATION.



equal to that of the corresponding gas in the mixture. In the aerotonometer
the blood is made to pass in a thin layer through a glass tube or tubes,

containing mixtures of gases of
known quantity and tension, and
it is arranged by practice that the
tension of the gases in the tubes
shall in the one case be greater,
in the other case smaller, than the
tensions of the corresponding gases
in the blood. The gases in these
tubes, after the blood has passed
through them, are analysed, and
from the alteration in the proj^or-
tion in the two tubes it is possible
to calculate the partial pressure
of the gases in the blood. The
aerotonometer is surrounded by a
water-jacket with a temperature
of 39°.

Figure 74 shows the con-
struction of a similar aerotono-
meter, devised by Fredericq.^ The
lilood of the animal is rendered
uncoagulable by the injection of
peptone, in order that the experi-
ment may be continued for an
horn' or two. The blood flows
directly from the carotid artery
through the instrument, and re-
turns to the jugular vein.
The aerotonometer contains, for example, at the commencement of the
experiment, oxygen 10 per cent., carbon dioxide 5 per cent., and nitrogen 85
per cent, of an atmosphere. The blood is passed through for one hour, and at
the end of that time the gases in the aerotonometer are analysed, aiid found to
be 14 per cent oxygen, 2 '8 carbon dioxide, and the remainder nitrogen. From
these figures it is concluded that the tension of the oxygen in the blood was
14 per cent, of an atmosphere, and that of the carbon dioxide 2'8 per cent, of
an atmosphere.

Bohr 2 had previously introduced a modified aerotonometer, the " hsemat-
aerometer," through which a constant and rapid stream of blood could be
maintained during each experiment (see Fig. 75).

What, then, are the tensions of the gases of the blood ? The results
obtained by different observers are very discordant, and have given rise to
considerable discussion.^ Nussbaum ^ determined simultaneously on a
dog the tension of the carbon dioxide in the blood from the right side
of the heart and in the air of the alveoli ; he found for the former a
pressure of .3-81 per cent, of an atmosphere, and for the latter 3'84
per cent. The tension of the carbon dioxide in normal alveolar air
would be lower, for it would Ije mixed to a certain extent with the




Fig. 73.— Piliiffer's aerotonometer.



^ CentralU. f. Fhysiol., Leipzig u. Wien, 1893, S. 33 ; Fredericq et Nuel, "Elements
de physiologie humaine," 3^ (Edition, 1893, p. 156.

^ Skandin. Arch. f. Fhysiol., Leipzig, 1891. Bd. ii. S. 238.

^ Bohr, Im. cit. ; Fredericq, CentralU. f. Physiol., Leipzig u. Wien, 1893, S. 33 ;
Haldane and Lorrain Smith, Journ. Physiol.., Cambridge and London, 1896, vol.
XX. p. 497.

* Arch. f. d. (jes. Physiol., Bonn, 1873, Bd. vii. S. 296.



CA USES OF THE EXCHANGE OF GASES.



777



tidal air. Wolffberg^ found that the expired air of a dog contained 2-8
volumes per cent, of carbon dioxide, or a tension of 21-3 mm. of mercury.
Strassburg^ found a tension of 5 '4 per cent, of an atmosphere for the





Fig. 74. — Fredericq's
aerotonometer.



Fig. 75. — Bohr's hflemataerometer.



carbon dioxide in the venous blood of the right side of the heart. This
value, higher than those obtained by Wolffberg and Nussbaum, could be
explained by the fact that the dog's lungs were not so well ventilated,
since tracheotomy had not been performed. In arterial blood Strass-
burg found the tension of carbon dioxide to be 2"2 to 3'8 per cent,
of an atmosphere, and for the oxygen Herter-^ obtained a tension of 10
per cent, of an atmosphere.

Very different results have been obtained by Bohr * in experiments
upon dogs. He obtained for the oxygen tension of arterial blood results
as high as 101 to 144 mm. of mercury, and in nearly every case the tension
was higher than the tension of oxygen in the air at the bifurcation of
the trachea, in one case by as much as 38 mm. As regards the tension of
carbon dioxide very discordant results were obtained. In eleven experi-
ments, in which the animal breathed pure air, the tension of the carbon
dioxide in the arterial blood varied between and 28 mm. of mercury; and
in five other experiments, when the air inspired contained carbon dioxide,

^ Artli. f. d. ges. Physiol., Bonn, 1871, Bd. iv. S. 478.
-/6iV/.,'l872, Bd. vi. S. 77.

^ Ztsclir.f. physiol. Chem., Strassburg, 1879, Bd. iii. S. 98.
•* Skandin. Arch. f. Physiol., Leipzig, 1891, Bd. ii. S. 236.



7 7 8 C HE Ml ST R V OF RESPIRA TION.

the tension of that gas varied between 0-9 and 57'8 mm. In the majority
of the experiments the air of the trachea contained carbon dioxide with
a higher tension than that of the gas in the blood. From these results
Bohr concluded that the exchange of gases between the air of the alveoli
and the blood in the lungs could not be accounted for by diffusion alone,
and he suggested that the tissues of the lungs played an active part in
the absorption of oxygen and in the excretion of carlion dioxide.

These results are so opposed to those obtained by Pfluger and his
pupils, that they naturally are subject to considerable criticism.^ In the
first place, it is to be noted that the respiratory quotients obtained by
Bohr during his experiments show values varying from 0'54 to I'Ol,
results which suggest imperfect and irregular ventilation of the lungs.
Hlifner ^ contests Bohr's results, and suggests that the irregularities in
the results are due to a want of equilibrium in the tension of gases in
the blood and in the air of the hsemataerometer. He finds that equilibrium
only obtains after several minutes and vigorous shaking of the blood in
the apparatus. Similar objections have been made by Fredericq,^ who
obtained, for the tension of oxygen in the peptonised arterial blood of the
dog, results always lower than the partial pressure of oxygen in the air
of the alveoli. Further, the results obtained by Fredericq for the carbon
dioxide agree with those given by Pfluger and his pupils.

The folloAviiig values are given by Fredericq * for the tension of oxygen
and of carbon dioxide in percentages of an atmosphere.

Doff.



External Air. Air of Alveoli. Arterial Blood. Tissues.

Tension of oxygen . .20-95 > 18 > 14 >

External Air. Air of Alveoli. A'enous Blood. Tissues.

Tension of carbon dioxide . 0-03 < 2-8 < 3-81-5-4 < 5-9

Quite recently Haklane and Lorrain Smith ^ have studied the tension of
oxygeii in the arterial blood of man by a new method, which, they maintain,
avoids the probable sources of fallacy in the aerotonometer. In this new
method the tension of oxygen in the arterial blood is calculated from the
percentage of carbon monoxide breathed by the subject of the experiment, and
from the final saturation of his blood with carbon monoxide. The resufis give,
for the oxygen tension of human arterial blood, a value of 26*2 per cent, of an
atmosphere, or 200 mm. of mercury. This vahie is about twice as high as that
of the oxygen in the pulmonary alveoli, and if it be correct, it follows that
diffusion alone does not explain the absorption of oxygen by the blood in the
lungs. Haldane and Lorrain Smith discuss some of the possible sources of
error in their metliod, such as ' the estimation of the saturation of the blood
with carbon monoxide, the dissociation of carboxyhsemoglobin, the effect of
dilution of the haemoglobin, and the excretion or oxidation of carbon monoxide ;



Online LibraryE. A. (Edward Albert) Sharpey-SchäferText-book of physiology; (Volume v.1) → online text (page 108 of 147)