E. A. (Edward Albert) Sharpey-Schäfer.

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endothelial cells of the capillaries. Hamburger and' Leathes con-
firmed these results, but showed that they could not depend on any
vital activity of the endothehal cells, since absorption took place with
equal rapidity even when poisonous solutions of sodium fluoride were

The great objection to these experiments is that they do not prove
conclusively absorption by the blood vessels. It is still possible that the
fluids may have been taken up by the subserous lymphatic network and
had not reached the thoracic duct during the experiment. This is an
objection raised by Cohnstein,^ who concludes from very similar experi-
ments that these flidds are carried away solely by the lymphatics. It
might be thought that this question could be easily decided by observing
whether fluids were still absorbed from the serous cavities after ligature
of both lymphatic ducts. I have made a number of experiments of this
description, but have failed to get decisive results. It is true that, after
ligature of both thoracic ducts as well as of the right innominate vein,
isotonic salt solutions were taken up fairly quickly from the serous
cavities. In none of these cases, however, could I be certain that the
lymph was absolutely shut off from the blood. As a rule I injected
on three succeeding days several hundred c.c. saline solution into the
peritoneal cavity, the last injection containing carmine granules in
suspension. On killing the dog two days after the last injection, the
peritoneal cavity was generally found to be empty, and carmine granules
could be traced along the glands of the anterior mediastinum, showing
that, in spite of the ligature of both lymphatic ducts, there had been a

^ Loc. cit. - Arch. f. d. ges. Fhysiol., Bonn, 1894, Bd. lix. S. 170.

'^ CentralU. f. Physiol., Leipzig u. Wien, 1895, Bd. ix.


passage of lymph upwards and through the chest. We must therefore
look to other methods to decide this question.

2. There is a whole series of experiments made by other observers
which I think prove conclusively the power of the blood vessels to take
up fluid from the tissue spaces. If an animal be bled several times, it
will be found that the blood obtained in the later bleedings is more
watery than that obtained at the beginning of the experiment. Now
this diminution of total solids in the blood seems to be due chiefly to a
dilution of the serum ; the serum contains less solids than before, and is
increased in volume relatively to the blood corpuscles. I may here
quote some observations which show this point.^

Dog 11'4 kilos. — Solids of serum = 7*72 per cent. Dog then bled to
220 CO. Thirty minutes later, solids of serum = 7"14 per cent.

In another experiment the solids of the serum were at first 6 "98 per cent. ;
after bleeding to 200 c.c. = 6'57 per cent.; after further bleeding to 100 c.c.
= 6*37 per cent.

In a smaller dog (6'5 kilos.), withdrawal of 150 c.c. blood reduced the
solids of the serum from 7*77 per cent, to 6*47 per cent.

It must be noticed that this attempt to regulate the amount of the
circulating blood by bringing it up to its normal volume is carried out
with great rapidity, so that it is, even while an animal is being bled,
found that the later portions of blood are more dilute than the earlier
portions. That the fluid wdiich is added to the blood in these cases is
derived from the tissues or tissue spaces, is shown by Lazarus-Barlow's ^
experiments. This dilution of the blood takes place even when the
thoracic duct is tied or when the lymph is conducted away by placing a
cannula in the duct, so that it cannot be due, as was formerly thought,
to an increased lymph flow into the blood.

3. In order to be absolutely certain of the power of the blood
vessels to take up isotonic solutions and dropsical fluids from the
tissue spaces, I carried out a series of experiments,^ in which I led
defibrinated blood through the blood vessels of amputated limbs. In
each case I had a double set of transfusion apparatus, and sent one-half
of the blood many times through a limb which had been rendered
dropsical by the injection of isotonic salt solution, while simultaneously
fluid was flowing at the same pressure through the other limb, which was
not dropsical, and thus served as a control. In each case the blood was
analysed and its haemoglobin estimated before the experiment, and from
both hmbs after the experiment. It was invariably found that, whereas
the blood which had passed from twelve to twenty-five times through
the sound limb had become rather more concentrated, the blood which
had passed through the oedematous hmb had taken up fluid from this
limb. I may here quote one of these experiments as an example : —

Total Percentage

Solids. of Oxyhemoglobin.

1. Blood before experiment . . 21*2 per cent. 100

2. After twenty passages through

normal leg . . . . 21-4 „ „ 103

3. After twenty passages through

oedematous leg .... 20-5 „ ,, 95*5

1 Tscherewkow, Arch. f. d. ges. Physiol., Bonn, 1895, Bd. Ixii. S. 304.
- Journ. Physiol., Cambridge and London, vol. xvi. p. 13.
^ Ihid., 1895, vol. xix. p. 312.

VOL. I. — 20


From a consideration of these facts we must conclude that lymph
and saline solutions, isotonic with the blood, may be taken up by the
blood circulating through the capillaries, and that this process may
occur comparatively rapidly.

Effect of intracapillary pressure. — We have already seen how
any excess of intracapillary pressure, such as accompanies plethora,
causes an increased transudation from the capillaries, so that the
volume of circulating fluid is diminished. Now we see that, on any
diminution of capillary pressure taking place, as after bleeding, the
fluid in the tissue spaces goes back into the vessels to make up for
the volume of circulating fluid lost. This wonderful balance between
capillary pressure and lymph production or absorption is, I think,
well illustrated by Lazarus Barlow's observations. This author has
shown that the slight plethora produced by wrapping up a limb in
Esmarch's bandage causes an appreciable increase in the transudation in
other parts of the body, so that the specific gravity of the tissues of the
upper limb for instance falls, while the specific gravity of the blood
rises. The reverse is the case when circulation is restored to a limb
which has been ke^Dt ansemic for an hour or two. Here considerable
hyperaemia of the affected limb is produced, and corresponding anaemia of
other parts of the body. We find, then, that absorption as well as trans-
udation through the capillary wall is determined by the intracapillary
pressure. When the pressure rises transudation is increased, when the
pressure falls absorption is increased. We have seen that the depend-
ence of transudation on capillary pressure is susceptible of a fairly simple
mechanical explanation. We have now to discuss the mechanism of the
absorption process.

Mechanism of absorption. — Filtration. — Is absorption effected by
the active intervention of the endothelial cells, or are there physical
factors at work which will serve to explain it ? An explanation of
absorption, which will strike anyone who investigates this problem, is
that it may take place in the same manner as lymph is produced,
i.e. by a process analogous to filtration. A series of mechanical
experiments by Klemensiewicz ^ would seem at first sight to show
that such a backward filtration is impossible. Klemensiewicz pomts
out that, if fluid be passing at a given pressure through a permeable
tube contamed witliin a rigid tube, transudation will occur until the
pressure of the transuded fluid is equal to that of the fluid flowmg
through. At a certain point in the experiment the pressure of the
transuded fluid will exceed the pressure at the outflow end of the
tube. The tube will collapse and the flow through it will be stopped.
He imagines that the same sequence of events occurs in the living
body in the presence of a considerable transudation. Arteries, capil-
laries, and veins are bathed in the transuded fluid. The fluid which
leaves the capillaries will, if a free outflow for it be absent, after
a time attain a pressure near that ruling in the capillaries and higher
than the venous pressure. The veins will therefore collapse, venous
obstruction will be produced, and the capillary pressure and trans-
udation will be higher than ever, so that we have a vicious circle
of events tending continually to increase the oedema of that part.
Now Klemensiewicz' objections are true only under one condition — i.e.
that the venous tulies should run freely through the lymphatic spaces of

^ Sitzungsb. d. Ic. Akad. d. JVissensch. , Wieii, 1881, Bd. Ixxxiv.; 1886, Bd. xciv.


the tissues. If, however, we consider a system in which the inner
tube is connected at various points in its circumference to the outer
tube by strands of fibres, it is apparent that a rise of pressure in the
space surrounding the inner tube will only serve to extend this tube
still further. No collapse will take place, but a back filtration will be
possible. If we cut sections of injected connective tissues, we find
that the capillaries are bound to surrounding parts by radiating fibres
which might possibly prevent their collapse under high extravascular
pressure. In the larger veins, on the other hand, the arrangement of
the fibres of the adventitia is circular and not radial, so that a high
extravascular pressure would apparently cause collapse of the veins.
From these anatomical facts one would conclude that a backward filtra-
tion is possible, provided that the extravascular pressure be raised in the
region of the capillaries. If, however, the pressure be freely propagated
through the tissues so as to affect the larger veins draining them, we
shall have collapse of the veins and increased oedema. Here, as in so
many other cases, we cannot get a decisive answer to our physiological
questions by purely anatomical investigation, but must have recourse to
physiological experiment.

The question that we have immediately to decide is, whether an
increased tissue tension augments or leaves unaltered the flow of blood
through the tissues, or whether it causes venous collapse and so
diminishes the flow. In the former case a back filtration would be
possible, and in the latter case impossible. I have investigated this
point in various regions of the body, e.g. the connective tissues of the
leg, the tongue as a type of muscular tissue, and the submaxillary gland
as a type of glandular tissue. In all these cases I have found that a rise
of tissue tension above the pressure in the veins causes collapse of these
veins, a rise of capillary pressure, and a diminished flow of blood through
the part. In these regions of the body, therefore, absorption of lymph
by a backward filtration is impossible.

Imbibition.— Hamburger,^ finding that serum and isotonic fluids are
absorbed from the peritoneal cavities of animals that have been dead some
hours, concludes that the life of the endothelial cell can have nothing to do
with the process, and ascribes the absorption to processes of capillary and
molecular imbibition, so that the absorption of fluids would be analogous
to the taking up of fluids and gases by animal charcoal. Though these
factors probably co-operate to a certain extent in the distribution of the
fluid through the tissues surrounding the serous cavities, it is evident
that they would be much more pronounced in dying and disintegrating
tissues, and could with difficulty explain the taking up of fluids by the
blood vessels. They would certainly not explain the wonderful balance
which exists between the intracapillary pressure and the amount of
fluid transuded from or absorbed by the blood vessels. What, then, is
the explanation of this absorption ?

Osmosis.— The explanation is, I beheve, to be found in a property
on which much stress was laid by the older physiologists, and which
they termed the high endosmotic equivalent of albumin. It must
be remembered that the older physiologists used animal membranes
in their experiments on osmotic interchanges. These membranes permit
the passage of water and salts, but hinder the passage of coagulable
proteid. The application of semipermeable membranes to the measure-

1 Arch.f. Physiol., Leipzig, 1895, S. 281.


ment of osmotic pressure has shown that the osmotic pressures of salts
and other crystalloids are enormously higher than those of colloids
such as albumin, and it has therefore been supposed that the osmotic
pressure of the proteids in the serum, being so insignificant, must be of
no account in physiological processes. The reverse is, however, the
case. Whereas the enormous pressures of the salts and crystalloids in
the various fluids of the body are of very httle importance for most
physiological functions, the comparatively insignificant osmotic pressure
of the albumins is of great importance — and for this reason. It has
been shown that bodies in solution behave in most respects like gases.
Now, there can be no difference in pressure between two gases in a vessel
which are not separated or are only divided by a screen freely permeable
to both gases. In the same way, if we have two solutions of crystallised
substances separated by a membrane which offers free passage to the
water and the salts on either side, there can be no enduring difference of
the osmotic pressure on the two sides, especially if a free agitation of
the fluids on both sides is kept up. The pressures on the two sides will
be speedily equalised, and then any flow of fluid from one side to the
other will cease. Now, the capillaries in the li^dng body represent such
a membrane. Leathes ^ has shown that, within five minutes after the
injection of sugar or salt into the blood vessels, their osmotic pressures in
the blood and lymph have become equal. Supposing, however, that we
have on one side of this membrane a substance to which the membrane
is impermeable, this substance will exert an osmotic pressure and will
attract water from the other side of the membrane with a force propor-
tional to its osmotic pressure. This attraction of fluid must go on until
all the fluid has passed through the membrane to the side where the
indiffusible substance is.

Now the capillaries of the limbs are almost impermeable to proteids.
In consequence of this impermeability, the fluid which is transuded
from the capillaries under pressure contains very little proteid. From
what I have just said, it follows that the proteids left in solution within
the capillaries must exert a certain osmotic attraction on the salt
solution outside the capillaries. It is easy to measure the value of this
attractive force. If we place blood serum in a small thistle funnel, over
the open end of which is stretched a layer of peritoneal membrane
soaked in gelatine, and immerse the inverted funnel into salt solution
which is isotonic or even hypertonic as compared with the serum,
within the next two days fluid will pass into the funnel and will rise in
its capillary stem to a considerable height. I have found that the
osmotic pressure of the non-diffusible portions of blood serum, measured
in this way, may amount to about 30 mm. Hg. The importance of
this fact is obvious. Although the osmotic pressure of albumin is so
insignificant, it possesses an order of magnitude comparable to that of
the capillary pressures; and whereas capillary pressure determines
transudation, the osmotic pressm^e of the proteids of the serum
determines absorption. Moreover, the osmotic attraction of the serum
for the extravascular fluid will be proportional to the force expended in
the production of this extravascular fluid, so that at any given time
there must be a balance between the hydrostatic pressure of the lilood in
the capillaries and the osmotic attraction of the blood for the smTound-
ing fluids. With increased capillary pressure we shall have increased

^ Joum, Physiol., Cambridge and London, 189.5, vol. xix. p. 1.


transudation, until we get equilibrium established at a somewhat higher
point, when there is a more dilute fluid in the tissue spaces, and there-
fore a higher absorbing force to balance the increased capillary pressure.
With diminished capillary pressure there will be an osmotic absorption
of salt solution from the extravascular fluid until this becomes richer in
proteids, and the difference between its osmotic pressure and that of the
intravascular plasma is equal to the diminished capillary pressure.^

Here, then, we have the balance of forces necessary to explain the
accurate regulation of the quantity of circulating blood according to the
conditions under which the animal may be placed, and it seems
unnecessary to invoke the aid of vital activity to explain the process.
Certain corollaries of this mode of explanation agree well with observed
facts of experiment. Thus the more impermeable the capillary the
smaller will be the amount of proteid exuded with the lymph. A
higher capillary pressure will therefore be needed in its production, and
there will be an equally high force tending to its reabsorption. A rise of
capillary pressure will only increase the amount of lymph in the
extravascular spaces to a certain extent, but will at the same time cause
this lymph to be more dilute, so that there will be a corresponding rise
in the force tending towards absorption. In consequence of this
sequence of events, considerable alterations of capillary pressure may
be produced in impermeable capillaries, such as those in the limbs,
without causing any appreciable increase in the lymph overflow from the
limbs. On the other hand, where the capillaries are very permeable,
very little pressure will be required to cause a transudation, since no
work is done in the concentration of a proteid solution, and we find as a
matter of fact, that capillaries where the pressure is lowest — i.e. in
the liver — are also those which are the most permeable. Here, too,
the absorbing force will be insignificant, since there is very little
difference in the percentage of albumin between liver blood and Hver

Moreover, since the pressure on the venous side of the capillaries is
considerably less than that on the arterial side, there will be a continual
exudation of a very dilute lymph from the arterial capillaries, and a
re-absorption of water and salts from this lymph in the venous
capillaries. The lymph, therefore, will assmne a composition such that
the osmotic pressure of its proteids approximates the mean capillary
pressure in the part where it is formed.

This osmotic difference between blood plasma and tissue fluid will
not serve to explain the absorption of proteids by the blood vessels nor the
absorption of serum from the serous cavities. It is difficult, however, if
not impossible, to prove that serum or proteid is absorbed by the blood
vessels. In some of my transfusion exjDeriments I have rendered a limb
oedematous by means of serum, and in these cases have obtained no
evidence at all of absorption by the blood vessels. There is no doubt
that serum may be absorbed from the pleural and peritoneal cavities,
but the absorption of these fluids is very much slower than the absorp-
tion of salt solutions, and is, in fact, so slow that the whole of it can in
most cases be effected by the lymphatic channels. A slow absorption of
serum from tissue spaces by means of the blood vessels is also physically
possible. As the cells of the tissues feed on the proteids of the fluid,

^ For a fuller discusslou of this point, cf. Science Progress, London, 1896, vol. v.
p. 151.


the serum will tend to become gradually weaker, so that the watery
and saline constituents corresponding to the proteid used up can then
be absorbed by the blood vessels in the way I have indicated.

The physical process which I have described above as causing the
absorption of lymph by the blood vessels must be in action at all times
in the body, and must therefore be a predominant factor in the process of
absorption. I have not been able to absolutely exclude the absorption
of proteids by the blood vessels, but, in the absence of direct experi-
mental evidence that such an absorption does occur, the physical factors
I have described in this chapter suffice to explain the phenomena of
absorption observed both under normal and under pathological conditions.

On" the Functions of the Lymph in the Nutrition of
THE Tissues.

The fact that the tissue cells are bathed by lymph and are
separated by this fluid and by the capillary wall from the blood,
shows that in all interchanges between blood and tissues the lymph
must act as the medium of communication.

I have already mentioned the irrigation theory of Bartholin, accord-
ing to which the nutrition of the tissues was carried out by a taking up
of soKds from the lymph as it left the blood vessels, so that only pure
water (or water and salts — Eudbeck) was left over to be carried away
by the lymphatics.

The observations of the Ludwig school on the lymph flow from the
limbs, showed clearly, however, that the nutrition of the tissues could
be normally carried out without any lymph flow at aU. The muscles
of a resting limb are taking up nourishment as well as oxygen from the
blood, and giving off their waste products, carbonic acid and ammonia,
although not a drop of lymph may flow from a cannula placed in a
lymphatic trunk of the limb. It is evident, therefore, that to a large
extent, at any rate, the giving up of nourishment by blood to tissues and
the taking up of the waste products of the latter through the inter-
mediation of the lymph, is carried out in the same way as are the gaseous
interchanges — i.e. by a process of diffusion.

I have abeady mentioned the experiments which demonstrate the
extreme rapidity with which diffusion takes place between the blood and
the lymph, so that, as Leathes points out, the time taken for the
equalisation of the constitution of the two fluids after introduction of
some diffusible substance into the blood is " inappreciable." There can
be no doubt that such changes are of great importance for the normal
metabolism of the tissues. Thus there has been considerable discussion
of late years concerning the supply of lime to the cells of the mammary
gland. Heidenhain pointed out that if the lime were supplied to the cells
by filtration, the whole flow from the thoracic duct would be inadequate
for the purpose. His conclusion that the lymph with its constituents is
therefore a secretion is, however, unnecessary. As the gland cell uses
up or turns out lime into the ducts of the gland, it will take up lime
from the adjoining lymph, thus lowering the partial osmotic tension of
the lime in its neighbourhood. There will be, therefore, a passage of
lime from blood to lymph by a process of diffusion, to supply the
deficiency. No flow of lymph at all is necessary to furnish the amount
of lime requii'ed by the gland cell.


The case is rather different when we come to consider the sux:>ply of
proteid food to the tissues. The diffusibility of the large molecular
serum proteids is so small that it may be disregarded, even in the
living body with its wonderfully perfect arrangement for allowing the
free contact of fluids without intermingling. Hence the only way by
which the tissues can obtain their supply of proteid is from the proteid
which has filtered through the vessel wall in the lymph. So far as the
proteid supply to the tissues is concerned, therefore, I believe that the
irrigation theory is correct, unless, indeed, we attribute to the vascular
epithelium the power of actively taking up proteid and transferring it
from one side of the vessel wall to the other in proportion to the needs
of the tissues.

Even under the former hypothesis, however, we could not, from the
amount of lymph draining away from a part, draw any conclusions as to
the amount of proteid which has been supplied to the part. As I
have above shown, the composition of the lymph is determined by the
permeability of the wall and the mean capillary pressure. If the com-
position of the lymph be altered after transudation, in consequence of
an active using up of the proteids of the tissue cells, the effective
osmotic difference between blood and lymph will be increased, and the

Online LibraryE. A. (Edward Albert) Sharpey-SchäferText-book of physiology; (Volume v.1) → online text (page 43 of 147)