RECORD OF MEDICAL SCIENCE.
ANATOMY AND PHYSIOLOGY.
Lectures on the processes of Repair and Reproduction after Injuries.
Delivered at the Royal College of Surgeons of England. By James
Paget, F. R. C. S., Professor of Anatomy and Surgery to the College.
LECTURE II.
Mr. President and Gentlemen,—In the last lecture I endeavour-
ed to establish the principle, that the power exercised in the repair of
injuries was the same as that put forth in the developement of the germ
from the lowest to the most perfect state in the full formed animal ; and
that this power was not determined by the fact of a higher or lower
position in the scale of animal life, but that it bears an inverse propor-
tion to the power expended in the developement of the germ. I omitted
all reference, then, to the amount of reparative power in the highest
vertebrata. In the warm-blooded animals the only parts capable of
being reproduced may be divided into three classes.
1.	Those in which each part is replaced by a repetition of the act
which formed the first; among these are, the blood and cuticle. 2.
Those of the lower organization or chemical composition—the gelati-
nous tissues and the osseous system. 3. Those accessories to the or-
ganic structures—the blood-vessels, nerves, lymphatics. These include
all that can be reproduced. I shall now devote the time allotted to this
lecture to ihe consideration of the materials necessary to the processes
of repair ; and I hope I shall not err in limiting myself to certain typical
instances. I propose to limit myself to wounds and fractures, and now
to speak especially of the materials necessary for the repair of injuries,
taking for illustration such wounds as are made in operations. Recent
improvements in surgery have shown how right Hunter was in laying
down the necessity of discriminating injuries—especially those which
are exposed to contact with the air. He says :—“ The injuries done
io sound parts I shall divide into two sorts according to the effects of
the accident. The first kind consists of those in which the injured parts
do not communicate externally, as concussions of the whole body, or of
particular parts, strains, bruises, and simple fractures, which form a
large division. The second consists of those which have an external
communication, comprehending wounds of all kinds, and compound frac-
tures.” And again, “ The injuries of the first division, in which the
parts do not communicate externally, seldom inflame ; while those of the
second commonly both inflame and suppurate.” Here he has ex-
pounded the whole art of subcutaneous surgery. I might remind you
of the difference of the processes of repair in simple and compound
fracture; although the simple may be attended with less violence, yet
from exposure to the air, if continued, they seemed to be far the worst;
even after extreme violence the symptoms of suppuration are far less
than in compound fractures. I found a number of examples of this
truth in some experiments I made to see how the tendons were healed.
In a certain number I made openings in the skin, and certainly the
wound externally was more severe than in subcutaneous wounds. In a
rabbit the tibialis anticus and the extensor longus digitorum were divided
on the right side, with a wide section through the skin, and on the left
with a subcutaneous section, through a small opening. Twelve days
after it was killed ;the subcutaneous wound had healed, andon the right
side there was a large collection of pus on the wound, covered in by
scabbing, and no trace of repair. The case is yet stronger, because in
making a subcutaneous wound, the violence is greater than in making
an open one. Still subcutaneous wounds seldom inflame ; while open
ones are much subject to this process and to suppuration. The reason
for this difference is, that the materials for the repair of the two kinds
of wounds are different. But before I speak of this I will just mention
the different modes in which open injuries are healed :—1st. By imme-
diate union. 2d. By primary adhesion. 3. By granulations. 4. By
secondary adhesions. 5. By scabbing.
The process of immediate union corresponds with that of Hunter’s
“union by the first intention,” and is accomplished by the effusion of
coagulable lymph between the two old surfaces of the wound. Hunter’s
account of it was, that a bond of union was formed by the blood extra-
vasated between the surfaces of the wounded parts . the blood organizes
itself, and becoming vascular, forms a connecting tissue between them.
Without doubt Hunter was in error in supposing that extravasated blood
is used commonly for this purpose; but I will speak first of what share
it really has. First, I may remind you of the evidences adduced in a
former course for coming to the conclusion that blood may be organized.
We may assume, that granules form a tissue and become vascular. I
have already mentioned several cases in which organization in the tissue
occurred—cases of clot forming in veins and becoming organized—cases
of clots of blood in the heart organizing into tumors,—and clots above
ligatures in tied arteries. Dr. Zwicky has clearly traced this process
till it became part of the fibrous cord. A case of this kind occurred in
the dura mater of an insane person examined by Mr. Holmes Coote,—
beneath it there was a distinct layer of clotted blood like that which is
effused in apoplexy of the cerebral membranes as described by Mr.
Prescott Hewitt. A number of small vessels passed from the dura
mater into this clot; and it was from these vessels, while filled with
blood, that I made this sketch (diagram exhibited.) Here it bears a
close resemblance to a sketch I have made of the vessels of an old adhe-
sion ; and the structure of the clot is interesting as being similar to the
material used for adhesion. When acetic acid was added to it there
appeared in it elongated corpuscles, and fibre with dark edges, bearing
no disiinct granules. No such structures are found in the ordinary pro-
ducts of inflammation ; but, from comparison, they bear an exact resem-
blance to the nuclei formed to develope ordinary cellular tissue. The
examination of this specimen shows one stage of the clotted blood be-
coming vascular in the formation of the cellular tissue, and is of the
same kind as that for the healing of subcutaneous injuries. With all this
evidence that the blood becomes organized, it was with surprise that I
found that blood effused and extravasated, can hardly ever become a bond
of union in injuries. In a large majority of cases no blood is extravasated.
Thus, in subcutaneous wounds of the tendons, it is very rare to find the
blood extravasated. I find out of twenty cases in which I have divided
the tendon Achillis in rabbits, only one in which a clot existed in the track
of the wound. In subcutaneous division of the tendon the same thing
holds, except where an artery is involved ; and amongst fractures there
is seldom so much blood effused as could form a bond of union. Here
is the tibia of a man, whose legs were crushed by a railway carriage, in
which there is no such quantity of blood as could form this bond.
These cases, then, prove the fact that extravasated blood is not neces-
sary as a bond of union. Still, when blood is extravasated, the question
arises, what becomes of it. If the blood be enough to form a large clot,
and the wound be exposed to the atmosphere, it is obvious that the blood
will be cast out of the wound. But under favorable circumstances, the
more ordinary mode is by absorption. But my observations have led
me to dissent from the opinion generally entertained of the absorption of
blood thus effused. The common idea is that the blood is absorbed and
lymph takes its place. But this can hardly be, since the absorption of
blood is a very slow process. In cases of fractures I have found the
blood not absorbed in five weeks ; and in a common leech-wound I have
found the blood corpuscles all as perfect a month afterwards. The truth
rather seems to be, that the blood is enclosed within the effused reparative
material, and is by it finally absorbed. In one case the tendo Achillis
was divided six days befor'e the death of the animal. As repair was
proceeding, on slipping through the length of the substance forming the
bond of union, I found a perfect clot of blood, which had been effused
from a large vessel, and the new material was formed completely round
it, and absorbed it. This only confirms me in the opinion that the in-
closure was formed of extravasated blood. In another case I found still
within the reparative substance traces of blood corpuscles imbedded
previous to its absorption. Still I should not be willing to believe that
it would never be organized. Hunter states that he has seen extrava-
sated blood forming a bond of union ; and one does sometimes find blood
s$> adhering to the bones that one can hardly believe it is about to be ab-
sorbed. The conclusion, then, as to the share blood takes in the re-
pair of injuries, is this :—
1.	That it is not essential or favorable to the healing of any wound.
2.	That most commonly, if existing in large quantities, and exposed,
it is ejected.
In favorable circumstances it may be absorbed, subsequent to the ad-
hesion of the new material.
4. It may become organized and form part of the reparative mate-
rial.
The material most commonly employed is that of coagulable lymph.
Our notions concerning the properties of this substance, when once
effused for the repair of injuries, are almost entirely from examinations
of the lymph effused in acute inflammations. The identity is far from
being proved, but their similarity is in many particulars evident, and es-
pecially in that both manifest, by their spontaneous coagulation, that
they contain fibrine. The coagulum, which is spontaneously formed
in reparative material, is identical with that of fibrine : chemically, too,
they appear the same. The natural tendency of coagulable lymph is to
develope itself into common fibro-cellular tissue ; but in certain cases
the developement of lymph passes beyond this form. Thus, for the
repair of bone, the lymph may proceed a certain distance towards the
developement of a fibrous tissue, or the lymph may proceed at once to
the formation of a nearly perfect cartilage, and this may ossify. Where
it is produced, it has characters adapted to the functions of the parts
that it unites. The bond for the union of a tendon is much tougher
than that for a common scar in the skin ; that in skin is tougher and less
pliant that that in mucous membrane, and so on. It has been thought
a nice question, whether these variations are determined by the proper-
ties of the lymph itself, or by an assimilating force in the parts in which
it is deposited. I have little doubt it is such a germ-power as that which
forms the embryo out of very different materials. We have yet no ob-
servations to -show a difference in the characters of the materials effused
for the repair of injuries of different parts, or indifferent circumstances ;
and yet such a difference, in even the original characters of the lymph,
is indicated by the fact, that it passes through two different ways of de-
velopement. The lymph, or new material, which is produced for the
repair of open wounds, generally developes itself into fibro-cellular tis-
sue through nucleated cells : that formed for the healing of subcutaneous
wounds as generally developes itself into the same tissue through the
medium of nucleated blastema.
It must not appear an objection, that there should be two modes of
developement to the same perfect tissue ; for this is usual, and has been
observed in nearly all the tissues. I spoke of it last year in relation to
the developement of the blood corpuscles, of which a first set are formed
from part of the embryo cells that form the germinal area or the whole
body of the embryo, and the second set are formed exclusively from the
corpuscles of lymph and chyle; and so it is with the cartilage, the mus-
cular and other tissues that are formed in the earliest periods of embryo-
life. At first they are developed from some of the embryo cells ; yet in
later life, no such cells are seen among them, but othejs appropriate !o
them, and of widely different form. So also in the bones, which at first
are developed through cartilage, but in their subsequent growth are in-
creased by ossification of fibrous tissue ; and in the repair of which we
shall find even more numerous modifications of these different develope-
ments.
(Here several diagrams were exhibited, of embryo cells, exudation
cells, and granulation cells.)
The cells first formed are round, very slightly granular, display a well-
marked cell-wall, and a clearly-defined round nucleus. Whether in
granulations, or in inflammatory exudations, such cells present a strik-
ing resemblance to the white corpuscle, or lymph corpuscles, in the
blood. In the developement of cellular tissue from these cells, the first
apparent change is in the nucleus. It becomes oval, even before the
cell does, and at the same time becomes clearer and brighter. One or
two nucleoli now appear distinctly in it, and soon it attenuates itself;
but this it does later, or in a less degree, than the cell; for a common
appearance is that of elongated cells bulged out at their middle by the
nucleus. With these changes each cell also is developing its structure ;
first becoming more granular, then having its cell wall thinned, or even
losing it. It elongates at one or both ends, and thus are produced a
variety of lanceolate cells, which gradually elongate towards the filamen-
tous form. As they thus change, they also group themselves, so that
the swollen part of each, at which the nucleus lies, is engaged between
the thinner parts of the two or more adjacent to it. The final disposal
of these nuclei is hard to discern. In many instances, they are deve-
loped into filaments, like those of elastic tissue. But in the develope-
ment of the cellular tissue formed in inflammation or granulating wounds,
the nuclei rather seem to waste, and be absorbed. Certainly such nu-
cleus-fibres are not found in scars lately formed, though common in those
of old standing. But, in their time, they display more organic activity
than the cells,—for they take the initiative in the multiplication of the
cells. In granulations, one may often find large compound cells, con-
taining eight, ten, or more, nuclei. These have been derived by subdi-
vision from the nucleus of the simple cell, and are probably destined to
be the nuclei of as many separate cells. Such is the process for the
developement of fibro-cellular tissue through nucleated cells, and though
some modifications of it take place, yet none of them affect the essential
(Characters of the process.
The developement of fibro-cellular or fibrous tissue through nucleated
blastema is observed in the natural developement of tendons and liga-
ments. It is the same which Henle regards as the only mode of deve-
lopement of the fibro-cellular and fibrous tissues. Schwann, on the
other hand, believes that there is no other mode than that which I have
just described. Certain it is, that both these modes of developement of
fibro-cellular or fibrous tissue maybe traced; nor can any better example
be selected than in the formation of scars from granulations, and of the
bonds that unite subcutaneous divided tendons. Of the union of divided
tendons I shall speak in a future lecture. For the present purpose, and
in relation to the developement of fibro-cellular or fibrous tissue from
nucleated blastema, it may be enough to state, that when the first effu-
sion of the products of the inflammation, excited by the violence of the
wound, is completed, then a quantity of finely molecular or dimly-shaded
substance, like homogeneous or dotted fibrine, begins to appear in the
space in which the bond of union is to be formed. This substance is
infiltrated in the tissue that collapses into the space between the retracted
•ends of the tendon. At first there is no appearance of nuclei or cyto-
blasts in it; it seems to be merely a blastema of fibrine ; but as it ac-
quires firmness and distinctness, the nuclei appear in it; they seem to
form out of collecting clusters of granules, and presently appear as oval
bodies, with dark hard outlines, soon becoming elongated, with clear
contents, without nuclei, irregularly scattered, but so firmly imbedded in
the blastema, that, in general, they cannot be dislodged. Commonly,
the application of acetic acid is necessary to make them distinct, by
making the intermediate substance transparent, while the nuclei them-
selves acquire dark edges and shrivel up a little. The nuclei undergo
little change, while the blastema in which they are imbedded, is ac-
quiring, more and more distinctly, the filamentous appearance, and then
the filamentous structure,—only they appear to elongate, and to attenuate
themselves, and to grow more irregular in their outlines as if by shrivel-
ling.
The blastema may become at length perfect fibro-cellular or fibrous
tissue. The final disposal of the nuclei is doubtless sometimes that
they are developed into the nucleus-fibres, and constitute some of the
various forms in which elastic yellow tissue is found mingled with the
proper white filaments. But, in the process of repair by tissue thus de-
veloped, as well as by that which is formed through cells, I believe that
the nuclei finally shrivel.
The deduction from these facts appear to be, that the material of re-
pair for subcutaneous wounds is developed into cellular tissue through
the formation of nucleated blastema ; while that for repair by primary
adhesions, and by granulation, is developed into the same through nuc-
leated cells. These instances, then, may enable us to conclude respect-
ing the existence or non-existence of inflammation in the healing of in-
juries. The material of repair in union by primary adhesion and gra-
nulations is the same, in appearance and mode of developement, as we
find produced in other conditions which are called inflammatory. But,
in the healing of subcutaneous wounds, we find a different material of
repair, which resembles, in both appearance and mode of developement
that which we find forming growths whose production is not attended
with any signs of inflammation. On these grounds, therefore, we are
justified in holding, generally, that inflammation ensues in the healing
by adhesion and by granulations, but does not exist in the healing of
subcutaneous wounds. Although inflammation may be deemed neces-
sary for the production of the lymph that may form adhesions or granu-
lations, yet we haye no evidence that the continuance of inflammation
is necessary for the organization of the lymph. Rather, the persist-
ence of inflammation seems to hinder the organisation of the lymph, to
keep it in a low state of developement, or to favor its degeneration—
Medical Times.