Alexis Thomson and Alexander Miles - Manual of Surgery

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The spaces between these loops are filled by cells of various kinds, the
most important being the _fibroblasts_, which are destined to form
cicatricial fibrous tissue. These fibroblasts are large irregular
nucleated cells derived mainly from the proliferation of the fixed
connective-tissue cells of the part, and to a less extent from the
lymphocytes and other mononuclear cells which have migrated from the
vessels. Among the fibroblasts, larger multi-nucleated cells--_giant
cells_--are sometimes found, particularly when resistant substances,
such as silk ligatures or fragments of bone, are embedded in the
tissues, and their function seems to be to soften such substances
preliminary to their being removed by the phagocytes. Numerous
_polymorpho-nuclear leucocytes_, which have wandered from the vessels,
are also present in the spaces. These act as phagocytes, their function
being to remove the red corpuscles and fibrin of the original clot, and
this performed, they either pass back into the circulation in virtue of
their amoeboid movement, or are themselves eaten up by the growing
fibroblasts. Beyond this phagocytic action, they do not appear to play
any direct part in the reparative process. These young capillary loops,
with their supporting cells and fluids, constitute granulation tissue,
which is usually fully formed in from three to five days, after which it
begins to be replaced by cicatricial or scar tissue.

_Formation of Cicatricial Tissue._--The transformation of this temporary
granulation tissue into scar tissue is effected by the fibroblasts,
which become elongated and spindle-shaped, and produce in and around
them a fine fibrillated material which gradually increases in quantity
till it replaces the cell protoplasm. In this way white fibrous tissue
is formed, the cells of which are arranged in parallel lines and
eventually become grouped in bundles, constituting fully formed white
fibrous tissue. In its growth it gradually obliterates the capillaries,
until at the end of two, three, or four weeks both vessels and cells
have almost entirely disappeared, and the original wound is occupied by
cicatricial tissue. In course of time this tissue becomes consolidated,
and the cicatrix undergoes a certain amount of contraction--_cicatricial
contraction_.

_Healing of Epidermis._--While these changes are taking place in the
deeper parts of the wound, the surface is being covered over by
_epidermis_ growing in from the margins. Within twelve hours the cells
of the rete Malpighii close to the cut edge begin to sprout on to the
surface of the wound, and by their proliferation gradually cover the
granulations with a thin pink pellicle. As the epithelium increases in
thickness it assumes a bluish hue and eventually the cells become
cornified and the epithelium assumes a greyish-white colour.

_Clinical Aspects._--So long as the process of repair is not complicated
by infection with micro-organisms, there is no interference with the
general health of the patient. The temperature remains normal; the
circulatory, gastro-intestinal, nervous, and other functions are
undisturbed; locally, the part is cool, of natural colour and free from
pain.

#Modifications of the Process of Repair.#--The process of repair by
primary union, above described, is to be looked upon as the type of all
reparative processes, such modifications as are met with depending
merely upon incidental differences in the conditions present, such as
loss of tissue, infection by micro-organisms, etc.

_Repair after Loss or Destruction of Tissue._--When the edges of a wound
cannot be approximated either because tissue has been lost, for example
in excising a tumour or because a drainage tube or gauze packing has
been necessary, a greater amount of granulation tissue is required to
fill the gap, but the process is essentially the same as in the ideal
method of repair.

The raw surface is first covered by a layer of coagulated blood and
fibrin. An extensive new formation of capillary loops and fibroblasts
takes place towards the free surface, and goes on until the gap is
filled by a fine velvet-like mass of granulation tissue. This
granulation tissue is gradually replaced by young cicatricial tissue,
and the surface is covered by the ingrowth of epithelium from the edges.

This modification of the reparative process can be best studied
clinically in a recent wound which has been packed with gauze. When the
plug is introduced, the walls of the cavity consist of raw tissue with
numerous oozing blood vessels. On removing the packing on the fifth or
sixth day, the surface is found to be covered with minute, red,
papillary granulations, which are beginning to fill up the cavity. At
the edges the epithelium has proliferated and is covering over the newly
formed granulation tissue. As lymph and leucocytes escape from the
exposed surface there is a certain amount of serous or sero-purulent
discharge. On examining the wound at intervals of a few days, it is
found that the granulation tissue gradually increases in amount till the
gap is completely filled up, and that coincidently the epithelium
spreads in and covers over its surface. In course of time the epithelium
thickens, and as the granulation tissue is slowly replaced by young
cicatricial tissue, which has a peculiar tendency to contract and so to
obliterate the blood vessels in it, the scar that is left becomes
smooth, pale, and depressed. This method of healing is sometimes spoken
of as "healing by granulation"--although, as we have seen, it is by
granulation that all repair takes place.

_Healing by Union of two Granulating Surfaces._--In gaping wounds union
is sometimes obtained by bringing the two surfaces into apposition after
each has become covered with healthy granulations. The exudate on the
surfaces causes them to adhere, capillary loops pass from one to the
other, and their final fusion takes place by the further development of
granulation and cicatricial tissue.

_Reunion of Parts entirely Separated from the Body._--Small portions of
tissue, such as the end of a finger, the tip of the nose or a portion of
the external ear, accidentally separated from the body, if accurately
replaced and fixed in position, occasionally adhere by primary union.

In the course of operations also, portions of skin, fascia, or bone, or
even a complete joint may be transplanted, and unite by primary union.

_Healing under a Scab._--When a small superficial wound is exposed to
the air, the blood and serum exuded on its surface may dry and form a
hard crust or _scab_, which serves to protect the surface from external
irritation in the same way as would a dry pad of sterilised gauze. Under
this scab the formation of granulation tissue, its transformation into
cicatricial tissue, and the growth of epithelium on the surface, go on
until in the course of time the crust separates, leaving a scar.

_Healing by Blood-clot._--In subcutaneous wounds, for example tenotomy,
in amputation wounds, and in wounds made in excising tumours or in
operating upon bones, the space left between the divided tissues becomes
filled with blood-clot, which acts as a temporary scaffolding in which
granulation tissue is built up. Capillary loops grow into the coagulum,
and migrated leucocytes from the adjacent blood vessels destroy the red
corpuscles, and are in turn disposed of by the developing fibroblasts,
which by their growth and proliferation fill up the gap with young
connective tissue. It will be evident that this process only differs
from healing by primary union in the _amount_ of blood-clot that is
present.

_Presence of a Foreign Body._--When an aseptic foreign body is present
in the tissues, _e.g._ a piece of unabsorbable chromicised catgut, the
healing process may be modified. After primary union has taken place the
scar may broaden, become raised above the surface, and assume a
bluish-brown colour; the epidermis gradually thins and gives way,
revealing the softened portion of catgut, which can be pulled out in
pieces, after which the wound rapidly heals and resumes a normal
appearance.

REPAIR IN INDIVIDUAL TISSUES

_Skin and Connective Tissue._--The mode of regeneration of these tissues
under aseptic conditions has already been described as the type of ideal
repair. In highly vascular parts, such as the face, the reparative
process goes on with great rapidity, and even extensive wounds may be
firmly united in from three to five days. Where the anastomosis is less
free the process is more prolonged. The more highly organised elements
of the skin, such as the hair follicles, the sweat and sebaceous glands,
are imperfectly reproduced; hence the scar remains smooth, dry, and
hairless.

_Epithelium._--Epithelium is only reproduced from pre-existing
epithelium, and, as a rule, from one of a similar type, although
metaplastic transformation of cells of one kind of epithelium into
another kind can take place. Thus a granulating surface may be covered
entirely by the ingrowing of the cutaneous epithelium from the margins;
or islets, originating in surviving cells of sebaceous glands or sweat
glands, or of hair follicles, may spring up in the centre of the raw
area. Such islets may also be due to the accidental transference of
loose epithelial cells from the edges. Even the fluid from a blister, in
virtue of the isolated cells of the rete Malpighii which it contains, is
capable of starting epithelial growth on a granulating surface. Hairs
and nails may be completely regenerated if a sufficient amount of the
hair follicles or of the nail matrix has escaped destruction. The
epithelium of a mucous membrane is regenerated in the same way as that
on a cutaneous surface.

Epithelial cells have the power of living for some time after being
separated from their normal surroundings, and of growing again when once
more placed in favourable circumstances. On this fact the practice of
skin grafting is based (p. 11).

_Cartilage._--When an articular cartilage is divided by incision or by
being implicated in a fracture involving the articular end of a bone, it
is repaired by ordinary cicatricial fibrous tissue derived from the
proliferating cells of the perichondrium. Cartilage being a non-vascular
tissue, the reparative process goes on slowly, and it may be many weeks
before it is complete.

It is possible for a metaplastic transformation of connective-tissue
cells into cartilage cells to take place, the characteristic hyaline
matrix being secreted by the new cells. This is sometimes observed as an
intermediary stage in the healing of fractures, especially in young
bones. It may also take place in the regeneration of lost portions of
cartilage, provided the new tissue is so situated as to constitute part
of a joint and to be subjected to pressure by an opposing cartilaginous
surface. This is illustrated by what takes place after excision of
joints where it is desired to restore the function of the articulation.
By carrying out movements between the constituent parts, the fibrous
tissue covering the ends of the bones becomes moulded into shape, its
cells take on the characters of cartilage cells, and, forming a matrix,
so develop a new cartilage.

Conversely, it is observed that when articular cartilage is no longer
subjected to pressure by an opposing cartilage, it tends to be
transformed into fibrous tissue, as may be seen in deformities attended
with displacement of articular surfaces, such as hallux valgus and
club-foot.

After fractures of costal cartilage or of the cartilages of the larynx
the cicatricial tissue may be ultimately replaced by bone.

_Tendons._--When a tendon is divided, for example by subcutaneous
tenotomy, the end nearer the muscle fibres is drawn away from the other,
leaving a gap which is speedily filled by blood-clot. In the course of a
few days this clot becomes permeated by granulation tissue, the
fibroblasts of which are derived from the sheath of the tendon, the
surrounding connective tissue, and probably also from the divided ends
of the tendon itself. These fibroblasts ultimately develop into typical
tendon cells, and the fibres which they form constitute the new tendon
fibres. Under aseptic conditions repair is complete in from two to three
weeks. In the course of the reparative process the tendon and its sheath
may become adherent, which leads to impaired movement and stiffness. If
the ends of an accidentally divided tendon are at once brought into
accurate apposition and secured by sutures, they unite directly with a
minimum amount of scar tissue, and function is perfectly restored.

_Muscle._--Unstriped muscle does not seem to be capable of being
regenerated to any but a moderate degree. If the ends of a divided
striped muscle are at once brought into apposition by stitches, primary
union takes place with a minimum of intervening fibrous tissue. The
nuclei of the muscle fibres in close proximity to this young cicatricial
tissue proliferate, and a few new muscle fibres may be developed, but
any gross loss of muscular tissue is replaced by a fibrous cicatrix. It
would appear that portions of muscle transplanted from animals to fill
up gaps in human muscle are similarly replaced by fibrous tissue. When a
muscle is paralysed from loss of its nerve supply and undergoes complete
degeneration, it is not capable of being regenerated, even should the
integrity of the nerve be restored, and so its function is permanently
lost.

_Secretory Glands._--The regeneration of secretory glands is usually
incomplete, cicatricial tissue taking the place of the glandular
substance which has been destroyed. In wounds of the liver, for example,
the gap is filled by fibrous tissue, but towards the periphery of the
wound the liver cells proliferate and a certain amount of regeneration
takes place. In the kidney also, repair mainly takes place by
cicatricial tissue, and although a few collecting tubules may be
reformed, no regeneration of secreting tissue takes place. After the
operation of decapsulation of the kidney a new capsule is formed, and
during the process young blood vessels permeate the superficial parts
of the kidney and temporarily increase its blood supply, but in the
consolidation of the new fibrous tissue these vessels are ultimately
obliterated. This does not prove that the operation is useless, as the
temporary improvement of the circulation in the kidney may serve to tide
the patient over a critical period of renal insufficiency.

_Stomach and Intestine._--Provided the peritoneal surfaces are
accurately apposed, wounds of the stomach and intestine heal with great
rapidity. Within a few hours the peritoneal surfaces are glued together
by a thin layer of fibrin and leucocytes, which is speedily organised
and replaced by fibrous tissue. Fibrous tissue takes the place of the
muscular elements, which are not regenerated. The mucous lining is
restored by ingrowth from the margins, and there is evidence that some
of the secreting glands may be reproduced.

Hollow viscera, like the oesophagus and urinary bladder, in so far
as they are not covered by peritoneum, heal less rapidly.

_Nerve Tissues._--There is no trustworthy evidence that regeneration of
the tissues of the brain or spinal cord in man ever takes place. Any
loss of substance is replaced by cicatricial tissue.

The repair of _Bone_, _Blood Vessels_, and _Peripheral Nerves_ is more
conveniently considered in the chapters dealing with these structures.

#Rate of Healing.#--While the rate at which wounds heal is remarkably
constant there are certain factors that influence it in one direction or
the other. Healing is more rapid when the edges are in contact, when
there is a minimum amount of blood-clot between them, when the patient
is in normal health and the vitality of the tissues has not been
impaired. Wounds heal slightly more quickly in the young than in the
old, although the difference is so small that it can only be
demonstrated by the most careful observations.

Certain tissues take longer to heal than others: for example, a fracture
of one of the larger long bones takes about six weeks to unite, and
divided nerve trunks take much longer--about a year.

Wounds of certain parts of the body heal more quickly than others: those
of the scalp, face, and neck, for example, heal more quickly than those
over the buttock or sacrum, probably because of their greater
vascularity.

The extent of the wound influences the rate of healing; it is only
natural that a long and deep wound should take longer to heal than a
short and superficial one, because there is so much more work to be
done in the conversion of blood-clot into granulation tissue, and this
again into scar tissue that will be strong enough to stand the strain on
the edges of the wound.

THE TRANSPLANTATION OR GRAFTING OF TISSUES

Conditions are not infrequently met with in which healing is promoted
and restoration of function made possible by the transference of a
portion of tissue from one part of the body to another; the tissue
transferred is known as the _graft_ or the _transplant_. The simplest
example of grafting is the transplantation of skin.

In order that the graft may survive and have a favourable chance of
"taking," as it is called, the transplanted tissue must retain its
vitality until it has formed an organic connection with the tissue in
which it is placed, so that it may derive the necessary nourishment from
its new bed. When these conditions are fulfilled the tissues of the
graft continue to proliferate, producing new tissue elements to replace
those that are lost and making it possible for the graft to become
incorporated with the tissue with which it is in contact.

Dead tissue, on the other hand, can do neither of these things; it is
only capable of acting as a model, or, at the most, as a scaffolding for
such mobile tissue elements as may be derived from, the parent tissue
with which the graft is in contact: a portion of sterilised marine
sponge, for example, may be observed to become permeated with
granulation tissue when it is embedded in the tissues.

A successful graft of living tissue is not only capable of regeneration,
but it acquires a system of lymph and blood vessels, so that in time it
bleeds when cut into, and is permeated by new nerve fibres spreading in
from the periphery towards the centre.

It is instructive to associate the period of survival of the different
tissues of the body after death, with their capacity of being used for
grafting purposes; the higher tissues such as those of the central
nervous system and highly specialised glandular tissues like those of
the kidney lose their vitality quickly after death and are therefore
useless for grafting; connective tissues, on the other hand, such as
fat, cartilage, and bone retain their vitality for several hours after
death, so that when they are transplanted, they readily "take" and do
all that is required of them: the same is true of the skin and its
appendages.

_Sources of Grafts._--It is convenient to differentiate between
_autoplastic_ grafts, that is those derived from the same individual;
_homoplastic_ grafts, derived from another animal of the same species;
and _heteroplastic_ grafts, derived from an animal of another species.
Other conditions being equal, the prospects of success are greatest with
autoplastic grafts, and these are therefore preferred whenever possible.

There are certain details making for success that merit attention: the
graft must not be roughly handled or allowed to dry, or be subjected to
chemical irritation; it must be brought into accurate contact with the
new soil, no blood-clot intervening between the two, no movement of the
one upon the other should be possible and all infection must be
excluded; it will be observed that these are exactly the same conditions
that permit of the primary healing of wounds, with which of course the
healing of grafts is exactly comparable.

_Preservation of Tissues for Grafting._--It was at one time believed
that tissues might be taken from the operating theatre and kept in cold
storage until they were required. It is now agreed that tissues which
have been separated from the body for some time inevitably lose their
vitality, become incapable of regeneration, and are therefore unsuited
for grafting purposes. If it is intended to preserve a portion of tissue
for future grafting, it should be embedded in the subcutaneous tissue of
the abdominal wall until it is wanted; this has been carried out with
portions of costal cartilage and of bone.

INDIVIDUAL TISSUES AS GRAFTS

#The Blood# lends itself in an ideal manner to transplantation, or, as
it has long been called, _transfusion_. Being always a homoplastic
transfer, the new blood is not always tolerated by the old, in which
case biochemical changes occur, resulting in haemolysis, which
corresponds to the disintegration of other unsuccessful homoplastic
grafts. (See article on Transfusion, _Op. Surg._, p. 37.)

#The Skin.#--The skin was the first tissue to be used for grafting
purposes, and it is still employed with greater frequency than any
other, as lesions causing defects of skin are extremely common and
without the aid of grafts are tedious in healing.

Skin grafts may be applied to a raw surface or to one that is covered
with granulations.

_Skin grafting of raw surfaces_ is commonly indicated after operations
for malignant disease in which considerable areas of skin must be
sacrificed, and after accidents, such as avulsion of the scalp by
machinery.

_Skin grafting of granulating surfaces_ is chiefly employed to promote
healing in the large defects of skin caused by severe burns; the
grafting is carried out when the surface is covered by a uniform layer
of healthy granulations and before the inevitable contraction of scar
tissue makes itself manifest. Before applying the grafts it is usual to
scrape away the granulations until the young fibrous tissue underneath
is exposed, but, if the granulations are healthy and can be rendered
aseptic, the grafts may be placed on them directly.

If it is decided to scrape away the granulations, the oozing must be
arrested by pressure with a pad of gauze, a sheet of dental rubber or
green protective is placed next the raw surface to prevent the gauze
adhering and starting the bleeding afresh when it is removed.

#Methods of Skin-Grafting.#--Two methods are employed: one in which the
epidermis is mainly or exclusively employed--epidermis or epithelial
grafting; the other, in which the graft consists of the whole thickness
of the true skin--cutis-grafting.

_Epidermis or Epithelial Grafting._--The method introduced by the late
Professor Thiersch of Leipsic is that almost universally practised. It
consists in transplanting strips of epidermis shaved from the surface of
the skin, the razor passing through the tips of the papillae, which
appear as tiny red points yielding a moderate ooze of blood.

The strips are obtained from the front and lateral aspects of the thigh
or upper arm, the skin in those regions being pliable and comparatively
free from hairs.

They are cut with a sharp hollow-ground razor or with Thiersch's
grafting knife, the blade of which is rinsed in alcohol and kept
moistened with warm saline solution. The cutting is made easier if the
skin is well stretched and kept flat and perfectly steady, the
operator's left hand exerting traction on the skin behind, the hands of
the assistant on the skin in front, one above and the other below the
seat of operation. To ensure uniform strips being cut, the razor is kept
parallel with the surface and used with a short, rapid, sawing movement,
so that, with a little practice, grafts six or eight inches long by one
or two inches broad can readily be cut. The patient is given a general
anaesthetic, or regional anaesthesia is obtained by injections of a
solution of one per cent. novocain into the line of the lateral and
middle cutaneous nerves; the disinfection of the skin is carried out on
the usual lines, any chemical agent being finally got rid of, however,
by means of alcohol followed by saline solution.

The strips of epidermis wrinkle up on the knife and are directly
transferred to the surface, for which they should be made to form a
complete carpet, slightly overlapping the edges of the area and of one
another; some blunt instrument is used to straighten out the strips,
which are then subjected to firm pressure with a pad of gauze to express
blood and air-bells and to ensure accurate contact, for this must be as
close as that between a postage stamp and the paper to which it is
affixed.

As a dressing for the grafted area and of that also from which the
grafts have been taken, gauze soaked in _liquid paraffin_--the patent
variety known as _ambrine_ is excellent--appears to be the best; the
gauze should be moistened every other day or so with fresh paraffin, so
that, at the end of a week, when the grafts should have united, the
gauze can be removed without risk of detaching them. _Dental wax_ is
another useful type of dressing; as is also _picric acid_ solution. Over
the gauze, there is applied a thick layer of cotton wool, and the whole
dressing is kept in place by a firmly applied bandage, and in the case
of the limbs some form of splint should be added to prevent movement.