View source for Talk:Paper - The relation between the size of the artery and the capillary bed in the embryo (1937)

THE RELATION BETWEEN THE SIZE OF THE
ARTERY AND THE CAPILLARY BED
IN THE EMBRYO

H. H. WOOLLARD anv J. A. HARPMAN
Department of Anatomy and Embryology, University College, London

THE work of Mall), Evans), Woollard(7), Hughes(3,4), and others has
established that there is a stage in the embryo after the formation of the
capillary bed when definitive arterial stems arise by enlargement and fusion in
part of the capillary bed, and coincident atrophy in other parts. The emergence
of these definitive stems is gradual and intermediate stages can be discovered
where the fusion of the capillaries is not yet complete. Observations of close
stages of injected preparations make it certain that this mode of development
is an accurate account of what happens.

Clearly it is to this stage of the erection of definitive stems that Thoma’s
laws apply, the earlier phase of capillary elaboration, it is generally agreed,
being an angioblastic response. Thoma’s laws have often been stated, but
perhaps they may be repeated here in the form quoted by Mall (5). The first law
is that increase in the size of the lumen of the vessel, or, what is the same thing,
the increase of the surface of the vessel wall, depends upon the rate of the blood
current. The second law states that the growth in thickness of the vessel wall is
dependent upon the tension. Further, the tension of the wall is dependent on
the diameter of the lumen of the vessels and upon the blood pressure. The third
law, which is the most contentious one, states that an increase of blood pressure
in an area leads to the new formation of capillaries. .

The background of these laws has been discussed several times, most
recently by Hughes (4,5), and it seems clear that endothelium can grow by its
own intrinsic properties. It is not the blood flow through them that induces
them to grow; this merely keeps up the regular pattern. Hughes and others
have, however, pointed out that this conclusion is not necessarily in conflict
with Thoma’s third law, since it is quite possible that in a particular field one
of the factors inducing new capillary formation might be an increase in the
blood pressure of the particular region concerned. This third law has been
invoked by Clark e¢ al(1), for instance, to explain the growth of the new capillaries which they observed in their experiments on the rabbit’s ear.

It is believed that the facts drawn from pathology and assembled by Thoma
himself have given an assured basis to the second of these laws. The most
spectacular example of the second law is found in the arterial-like changes
The Capillary Bed in the Embryo 19

which a vein undergoes when it is subjected to the forces operating upon an
arterial wall by introducing it into an arterial stem.

Thoma’s work on the area vasculosa of the chick has long been regarded as
the principal support of the first of these laws, but it is true that for the most
part in the embryological field this law has been based on its interpretative
value rather than supported by quantitative investigation. Hughes in his
latest work (which we have had the privilege of seeing in manuscript) has
attempted to make good this defect by a very extensive quantitative investigation on the blood vessels of the developing chick. He has taken as his source
of observations the marginal velocity of the corpuscles wherever measurable in
arteries and veins. Owing to‘the very great difficulties encountered in plotting
vessel size against such velocities as can be seen and measured, there is a
considerable degree of inconstancy in the results obtained.

PRESENT INVESTIGATIONS

It occurred to us that in fixed injected specimens it might not only be
possible to make more accurate measurements, but also that it would be much
easier to measure the diameter of the entering and leaving blood vessels and the
area of the capillary bed which they supplied. This implies of course the
assumption that the amount of blood delivered to the capillary area would be
proportional to its area and would also be proportional to the cross-sectional
area of the vessel of supply.

There were available to us a number of pig embryos which had been
injected while still living with indian ink. These we had used previously for the
study of the development of the blood vessels of the forelimb. The injected
specimens had been fixed in formalin and cleared through oil of wintergreen.
Out of the material we selected a number in which the limbs had been detached
and in which the filling of the vessels appeared to be complete.

Under the microscope, by means of camera lucida tracing, it was possible
to measure the diameter of the entering vessels and the area covered by the
injected capillaries. Areas were measured either by using squared paper or by
means of a planimeter. The diameter of the entering blood vessel was obtained
in the same way.

The graph shown as Fig. 1 is the outcome of these measurements upon
arteries and capillary beds. It will be seen that at the stage when the arteries
are becoming differentiated fromthe capillary bed the graph shows a close
approximation to a straight line. These measurements cannot claim any great
precision, for the pressure (blowing by the mouth) at which the injections were
made might differ somewhat, the resistance to distension perhaps would vary
in the different embryos, and the state of contraction or dilatation of the
capillary bed might not be the same. These considerations can be used either to
suggest that the agreement between vessel size and capillary bed is greater than
appears, or that the relationship is more apparent than real. It is also to be

2—2
20 H. H. Woollard and J. A. Harpman

observed that the graph shows a change from the linear relation at the beginning and towards the end of the instances plotted. The earlier curve occurs presumably because then our examples fall within the period of the angioblastic response which is forming the capillary bed, and the second later curve
because we now reach toward the more stable relation that arises as the rate
of growth declines. The curve hereafter will approach more and more to the
horizontal as growth becomes slower and slower.

 

 

 

 

 

 

 

Area of capillary bed in sq. mm.

 

 

 

 

 

 

 

 

10 5
e
e
0
0 0-05 1-0 0-15
Cross sectional area of artery in sq. mm.

Fig. 1

The illustrations which accompanied our earlier paper (7) could be used also
for the construction of a graph, since in each the capillary bed and the size
of the artery had been accurately drawn. Since, however, they had not been
all drawn at the same degree of magnification it was necessary, in order to make
a graph, to plot the ratio of the size of the artery to the area of the capillary
bed against the length of the embryo. This gave us a straight line, but the cases
illustrated are too few to justify publishing the result.

In these computations we have measured the area of the capillary bed
rather than its volume. Obviously it would have been more satisfactory to
have used this latter measurement. In practice the difficulties of getting an
accurate measure of cubic capacity would have been so great that many new
The Capillary Bed in the Embryo 21

errors would have been introduced. The measurement of the area was really of
more value.

_The measurements obtained for the veins were unsatisfactory. In our
preparations the diameters of the veins change frequently and irregularly along
their course. Further, sometimes a vein which may have attained a relatively
considerable volume along its course might relapse into a capillary network
again in the vicinity of the body wall. However, when selecting older specimens
in which these difficulties did not occur, it can be said that there is some
correspondence between vein size and the area of the capillary bed.

After taking into account the various sources of error in these measurements,
and after the admission that they measure only indirectly the rate of blood
flow into a capillary bed, we believe that they help us to justify the validity
of Thoma’s law in regard to the development of blood vessels in the embryo.
The matter seems to us of some importance. Frequently the development of
blood vessels, for example those of the lower extremity, are described as
exhibiting a series of changes wherein the pattern of large definitive stems
changes in a manner for which there seems to be neither functional nor
morphological reason. If one accepts Thoma’s laws, or even only the first one
of them, one must feel some scepticism about these apparently inexplicable
changes.

The evidence behind these laws of Thoma is now considerable. There is the
great work of Mall(5) on the structural unit of liver, wherein he showed by
numerous measurements how Thoma’s laws hold throughout development, and
serve to ensure the functional value of the adult arrangements. Upon the
development of veins the laws of Thoma seem much more doubtful. Even in
the earlier stages of development the correspondence, measured as described
above, between size of vein and capillary bed is not close and in the adult the
dimensions of the venous wall, the size of the vein, and the pressure within it
have only the most general relationship to one another.

SUMMARY

1. Using the injected blood vessels of pig embryos at different ages the size
of the artery and the area of the capillary bed supplied in the limb have been
measured.

2. Plotting these against each other an approximate straight line has been
obtained within certain limits.

3. Within these limits it has therefore been concluded that the size of the
artery depends on the amount of blood passing unit cross-sectional area in unit
time, or the rate of the flow of blood which is Thoma’s first law.

4, The same observations applied to veins at the same stage of development
exhibit only very slight agreement.
22 H. H. Woollard and J. A. Harpman

REFERENCES

(1) Cuarx, E. R., Hrrscuter, W. J., Rex, R. O., Kirsy-Smitu, H. T. & Smiru, J. H. (1931).
“Observations on the ingrowth of new blood vessels into standardized chambers in the
rabbit’s ear, and the subsequent changes in the newly grown vessels over a period of
months.” Anat. Rec. vol. L, p. 129.

(2) Evans, H. M. (1912). “‘The development of the vascular system.” Manual of Human Embryology, vol. 11, p. 570. Philadelphia and London: Keibel and Mall.

(3) Huauss, A. F. W. (1935). “Studies on the area vasculosa of the embryo chick. I.” J. Anat.,
Lond., vol. Lxx, p. 76.

(4) (1937). ‘‘Studies on the area vasculosa of the embryo chick. II.” J. Anat., Lond.,

(in the Press). These papers contain all the relevant literature on this subject.

(5) Mata, F. P. (1906). ‘A study of the structural unit of the liver.” Amer. J. Anat. vol. v,

p. 227.

(6) Sastn, F. (1922). “Direct growth of veins by sprouting.” Contr. Embryol. Carneg. Instn.
No. 65, vols. xmI-xtv, p. 1.
(7) Woottarp, H. H. (1922). ‘The development of the principal arterial stems in the forelimb of
the pig.” Contr. Embryol. Carneg. Instn. No. 70, vol. xiv, p. 139.