Pathology Process Of Repair
cells blood vessels tissue surface bone skin granulation granulations growth
PATHOLOGY PROCESS OF REPAIR - the spontaneity of certain polyps under injury is a good example of the indwelling power of all the cells and tissues to return to the established order, to the order and harmony which had been slowly acquired, and of which the memory is vividly retained. Trembley cut a hydra longitudinally, and " in an hour or less," says Paget, " each half had rolled itself and seamed up its cut edges so as to be a perfect hydra. He split them into four ; he quartered them ; he cut them into as many pieces as he could ; and nearly every piece became a perfect hydra. He slit one into seven pieces, leaving them all connected by the tall, and the hydra became seven-beaded, and he saw all the heads eating at the same time. He cut off the seven heads and, hydra-like, they sprang forth again." The recovery of perfection may be more gradual. Thus, Sir J. G. Dalyell (as quoted by the same writer) cut a specimen of Hydra tuba in halves ; each half regained the perfect form, but only very slowly, and, as it were, by a gradual improvement of parts that were at first ill formed. In 7'ubularia indivisa, after the natural fall of its head, the stem was slit for a short distance down ; an imperfect head was first produced, at right angles to the stem, froin one portion of the cleft ; " after its fall another and more nearly perfect one was regenerated, and, as it grew, im-proved yet more. A third appeared, and then a fourth, which was yet inore nearly perfect, though the stein was thick and the tentacula imperfect. The cleft was almost healed, and now a fifth head was formed, quite perfect ; and after it, as perfectly, a sixth and a seventh head. All these were produced in fifteen months." This spontaneity resides in every living thing, and its efforts are directed by- the memory of what the species bad come through in reaching its place in the scale of organization ; it is able, indeed, to make perfect reparation for injuries or losses only where the cells are little differentiated into tissues, or where the tissues are little specialized for diverse func-tions. In all animals, and most notably in the higher, this spontaneity is most effective for repair in the periods of development and growth. With reference to the degree of reparative power possessed, Paget formulates the rule as follows ; " The amount of reparative power is in an inverse ratio to that of the development, or change of structure and mode of life, through which the animal has passed in its attainment of perfection, or on its way thitherward."
Healing by Granulations. - It will now be convenient to advance C medias TO, and to give some account of the process of repair in man, where there is a breach of continuity in the course of the r blood-carrying and lymph-carrying vessels, of the nerves, sinews, binding tissue, bone, fat, and skin. What is the effort that they each and all make to adapt themselves to the circumstances, in the case, let us say, of ft stump after amputation ? (The repair be-tween the two ends of a broken bone will be discussed separately.) Disregardin, the cases where the most perfect coaptation of parts is secured bby the surgeon, and selecting the extreme case where the wound is "left to granulate," the following is the order of events. The divided vessels being sealed up either by ligature or by clots of blood (which are in the end absorbed), there oozes from the raw surface a blood-tinged serous-looking fluid. Becoming paler by degrees, it sets ou the surface as a greyish-white film or glazing, especially on the exposed surface of muscle. The film of surface-glazing will be found to contain numerous corpuscles embedded in it resembling the colourless corpuscles of the blood. They have probably the same formative or reparative value as the granulation-cells proper, but it will appear from the facts about to be given that they are practically superseded by the latter in all cases where a wound is " left to granulate." After an interval of two or three days of apparent rest reddish points are seen on the edges of skin, on the nniscular substance, and on the marrow of the bone ; these are the beginnings of the granulation-tissue, which in the end covers the whole surface and ..rows until it fills up the gap somewhat beyond the level of the edges of skin. When the growth of g,ranu-lations projects considerably beyond the skin it is known as "proud flesh." Usually the surface begins to skin over when the defect of substance has been sufficiently inade good, the new skin showing as a delicate bluish border or frill to the old skin. This frill becomes broader and broader until the growing points meet in the centre, and the continuity of thc skin is restored. 14leanwhile the granulation -tissue beneath has been changing into more charac-teristic forms of mature tissue, although the status quo antea is never quite restored.
Notwithstanding the regularity of this process, arid its daily occuiTenee in surgical practice, there is an almost incredible amount of conflicting opinion as to its details, - radical differences as to the source or sources of the reparative material, and as to the mode of development of the new blood-vessels and of the new skin and these differences of opinion must be the measure of the difeculty of analysis where the interference takes place in the highly com-plex and subtly integrated life of man. Direct observation of the reparative process does not of itself suffice to discover the law of it ; it is necessary to seek elucidation from the nearest analogies, both among the regular processes of life and growth and among the deviations therefrom. Among the former there is in particular one rich source of analogous detail to be found in the periodical new formation on the surface of the uterus for the purposes of the embryo - in the placenta ; among the latter are certain kinds of tumours and cysts. Hunter sought for a parallel to the 11CW vessels of granulation-tissue in the first formation of vessels in the embryo ; but these arise in the continuity of development, and not as a somewhat abrupt incident in the mature life. On the other hand, the formative process of the placenta is an example - and a unive example - of an extensive new growth of vascular tissue occurring periodically in the adult, and as somewhat of an interruptiou ou the ordinary course of life. It matters little for this parallelism whether we accept thc extreme position of Ercolani, that a total destruction of the uterine mucosa precedes the placental new growth, or whether we adopt the more likely view that the new formation takes place tinder an intact surface. Ili either case we have to do with a remarkable spontaneity of the body, a spontaneity which reveals the indwelling power of the tissues, and especially the vessel-making power.
..-//m/o;ty ty. Placeottal 11CW Formations. - The first adaptation:3 for • the placenta are not in the pre-existing vessels, Init in the pre existing tissues around. The elon-gated and almost fibre-like cells become more plump, they join to form cylinders of nucleated proto-plasm, the adjoining cylinders open out to form meshes between them, and al] this takes place in the intervals between the vessels and their capillaries (fig. 1). The cells of the tissue return to that embryonic state which preceded the formation of blood -vessels, supplying their own juices, as it were, and opening out so as to form plasmatic canals in their midst. In the placental rudiment it is a mucus-like albuminous fluid that they mostly yield, but there is some evidence that they also yield blood-corpuscles. Meanwhile, the same process of enlarge-ment has been taking place in the cells immediately surrounding the blood-vessels ; and at a later stage it is the perivascular cells that keep up this acti-vity (fig. 2). The phase of development in which the cells supply their own juices, retaining them in meshes of the tissue, is succeeded by a new formation of VCS-sels, a more pertnan-cut provision, Certain tracts of cells are told off to form the walls of blood-vessels, the chan nel of the vessel being the space between two such adjoining tracts (fig. 3). These selected cylinders of cells become the new and enlarged system of blood-vessels, adequate to the requirements of the part. In this placental process the original capillaries play a very subordinate part ; the thin cell-plates that form their walls are far outrun in the hyperplastic race by the cells of the tissues around, and it is the latter which furnish the materials for the new vessels. Tlurt which distinguishes the placental new formation is the enormous thickness of the walls of the new vessels and their terminal capillary loops. It remains to consider whether this pla-cental new formation of vascular tissue - the only instance of the kind in the ordinary course of adult life - offers any help to the understanding of granulation-tissue.
l'endon in a G-ranulating Stump.--It is at once evident that the tissues of a stump_after amputation have a very- unequal value for formative purposes, and probably all of them a lowee value than the uterine tissue, which is at no time far removed from embryonic characters. This inequality is seen in the onler in which granula-tions appear - first on the vascular layer of the skin, on the ends of muscle, and on the marrow of bone, and last on the ends of tendon. The attempt of a severed tendon to cover itself with a cap of granulations is somewhat feeble, and its slowness gives us an opportunity of ;narking points of detail. Tendon consists of wavy bundles of fibres in close order, and in fnll-grown animals its cellular elements are reduced to sniall dimensions. They are thin plates folded round the bundles, presenting in the face view the appearance in a, fig. 4, and in the side view the appearance b, fig. 4. I 11 the granulating end. of a tendon the appearance is that of e. fly. 4 : the thin ;dates have become solid or cubical. and where they have increased in number the free end of the tendon they other tissues of the part have already done the same, some much earlier and more extensively than others. Wherever capillaries are most numerous there the cellular activity is greatest, the cells nearest to the Iva]] of the capillary becoming More plump or more embryonic. The cellular material for the purposes of repair is supplied first around the severed vessels (according to some it is even supplied from within the vessels in the form of colourless blood-corpuscles) of the highly vascular muscle, of the marrow of bone, and of the subcutaneous tissue, and ultimately even by the ends of the tendons. In the placental process the formative materials had been furnished much more evenly over the whole area.
Blood-vessels of Repair. - The next step is towards the nutrition of the formative cells. 'Whether their nutrition is for a time plas-matic (as in fig. 1, from the placental growth) does not appear •, about the third day the fonuative tissue begins to be furnished with numerous bl ood-vessels. Their for-mation is very diffi-cult to observe in young granulations ; in older granulation-tissue they have the appearance drawn in fig. 5, a series of parallel tubes mak-ing straight for the surface, ramifying on the same, joining by numerous loops near the surface, and of unequal calibre throughout their course, being widest on or near thesurface.
These vessels are different in several respects from the vessels in a vascular area of the normal organism of corresponding extentomless it be in the decidua uterina. They are not branching arterioles ending in a line capillary network, hut they are of somewhat miiform and exceedingly simple structure throughout, and their calibre is often greater at the distal than at the proximal end. \Ve have next to consider how these vessels have originated.
The youngest granulations that can be prepared for examination consist of a imiform mass of cells, mostly round, and of somewhat wide vascular channels separated from the mass of cells by thin walls of more elongated cells (fig. 6). The most probable analogy for these new and wide vessels is not the embryo nor the tadpole's tail, but the placenta ; that is to say, certain of the cells along pre-determined lines agininate to form the opposite sides of a tube, 'be-coming adai ded slmpe to that end (fig. 3). According to 1;illroth, there is hardly ever in granulations an extension of the pre-cxisting capillaries by outgrowth of branching cells fi•ont their walls such stances are so little ana-logous in the two cases that this statement may be readily credited. How the new vessels join on to the old is not easily made ont, whether in the!. placenta or in granula-tions.
.A.s the granulations get older, the vessels acquire a considerable longitud-inal coat of spindle-cells. The individual granula-tion-points on the surface become fused into a more uniform fleshy stratum, the lower layers contract as the cells approximate to fibrous tissue, and skin begins to form OD the surface. If a healed surface be examined long after, in micro-scopic sections through the sk-in and subjacent tissue, the parallel vessels will still be observed running at intervals towards the surface, only more obliquely than in tlie granulation-tissue. They are invested by a certain quantity of fibrous tissue arranged parallel to their course, while all the rest of the space between two of them is occupied by horizontal lines of fibrous tissue, with spindle shaped. cells regularly among the blindles. This change has been, first of spherical granulation - cells into spindle-shaped cells, with development of intercellular or perinuclear substance (fig. 7), and then fibrillatiou of the latter. It is worthy of note that a development into elastic fibres goes on in the scar for months or even years after healing is complete. Ilairs, hair -follicles, and se-baceous glands are not repro-duced in the skin of scars, nor are sweat-glands. On the other hand, fat develops readily in the usual situations.
,S'uppuration Pepair. - Meanwhile there has been a remarkable concomitant of the growth and adaptation of the reparative material, namely, a flow ofpus or ?natter from the surface. :Matter or pus varies in its physical characters somewhat ; it may be creamy and yellowish-white (pus laudabile) or greenish-white, or it may be thin and watery or more viscid. It has an alkaline reaction and. a faintly sweetish odour. Standing in a vessel, it separates into two parts, - a supernatant fluid or serosity, clear, and of a yellowish tint, and a sediment of pus-cells. The serum coagu-lates when boiled, and it may even happen that a fibrinous clot forms in pus after death, just as in drawn blood. The serum of pus contains from 1 to 4 per cent. of albumen, and very much the same salts as blood-serum. The cells of - pus are spherical elements of some-what uniform size, of the greyish colour of protoplasm, grannlar on the surface, and disclosing the presence of two, three, or four nuclei when treated with acetic acid (fig. 8). They are capable of ainceboid movements, and they may be seen to take into their substance such particle?, as charcoal with which the wound may be dressed.
Physiological Analogy of ALS. -PI1S is a very remarkable adjunct of the reparative process - to go no farther into the inflammatory processes for the present. The pns-cells are evidently a condition or product of the - granulation -cells on the extremities and sides of the vascular out-growths, and they are detached from these situations, carrying with them a certain amount of fluid. Is there anything analogous to this in other formative processes of the body ? The following analogy is very close in some at least of the circmnstances. The d interior of a cyst removed by operation froni the neck region is - found to be covered with vascular tufts, which have precisely the character of granulations as regards the blood-vessels. Each vas-cular tuft is covered by a cap of cells like a granulation, and the same investment of cells can be followed as a cylindrical column down the vessel into the depth of the eyst-wall. These cells are somewhat peculiar. They are cubical or polyhedric elements, with a integrated, the nucleus being cleft into fragments, which afterwards coalesce, while the cell-substance tlowa in the form of spherical or oval or pear-shaped vesicles of a reddish tint (fig. 9, b). The cyst is a blood-eyst, - its con tents, a clear brownish fluid with many red blood-disks floating in it, having been produced by the disintegration of the cells covering the vascular tufts. The cells are Inematoblasts; their cell-substance is disengaged in drops which afterwards become red blood-disks, and their nucleus, after being cleft into several frag-ments of unequal size, is remade and survives as a cell of the size of a pus-cell, and containing several nuclei like a pus-cell (fig.9, c). This is a curious instance of blood-making froin connective-tissue cells late in life, and it is not so much inexplicable in its characters as it is rare in its occurrence. The formation of pus on the granu-lations of repair is one of the commonest of incidents, but it is open to elucidation even by a rare analogy. In the one case a blood-like fluid is formed, and in the other pus ; the fluid part of pus corresponds to the plasma together with the red blood-disks ill the cyst, and the cellular part of pus, the pus-corpuscle, corresponds to the surviving but broken-up nucleus of the lnernatoblast. The granulation-cell is comparable to the perivascular cell of this blood-making process, and in passing into the condition of a pus-cell with several small nuclei it disengages merely a fluid plasma and no red blood-disks. The cells of the injured part having returned to an embryonic state, their first activity is a revival of' early embryonic activity ; if they do not make blood, they yield that which may be regarded as its substitute, namely, pus.
This analogy will appear all the closer from a consideration of another eyst. In this new growth, Which occurred under the skin of the back, and was removed, like the former, by operation, the wall is lined by a certain thickness of tissue which is practically the same as the granulation-tissue of repair ; there are the same parallel vessels ending in loops, the same cells, and the same deliquescence of the surface. The fluid in the cyst is indeed the result of this liquefaction - a somewhat turbid brownish fluid. In a small recess of the cyst there is a. formation of a considerable layer of epidermis-like scales on the surface. One important point of difference is that the deeper layers of cells show no tendency to become siindle-shaped, to take a transverse order in the intervals between the parallel vessels, and so to become fibrous tissue. On the contrary-, one finds in the depths of the tissue the stems of vessels surromided by zones of young cells, perivascular sources of the new growth by which the loss of substance around the terminal loops of the vessels is constantly made good. On these terminal loops the process is not one of pus-formation, nor is it altogether one of' blood-formation as in the former cyst ; but it is an intermediate process which helps us still further to understand the significance of the pus in repair. The new formation is comparable to that of the blood-cyst in the obvious perivascular grouping of its cells, and it is comparable to the granulations of repair in the forms of its cells ; and it ticus supplies the link between the blood -yielding tufts of the former and the pus-yielding vascular points of the latter. "What, then, is the nature of the deliquoscence in the interior of this cyst ? It is partly blood; and there may be seen also the large cells from whose proto-plasm the blood-disks have been derived. There arc also seen the remarkable cells with nucleus cleft into three or four, so like the cells of pus (fig. 10, b); the latter are the surviving nucleus of the lilematoblast, the peculiar form of which is best explained by watching the more perfect process of blood-formation on the wall of the blood -cyst. Fewer of the cells in the second cyst undergo this transformation ; fewer of them ever attain the perfect form of Incinato-blasts so as to be able to undergo it. For the most part they pursne a devious development, and it is in this that they resemble granidation-cells. The differ-ence is only one of degree ; the type or law of the process the lnematoblastic type, which may be more or less perfectly attained. We are accordingly confirmed in the impression that pus-cells are the surviving nuclei of embryonic cells whose perfect law blood-making, and that the fluid which accompanies them is the eell-pro-toplasm whieh has failed to cliseng,age itself in the form of individual buds that easily pass into red blood-disks, but has become a veritable albuminous l'us, then, inay be said to be blood absolutely wanting in red blood-disks, and with the colourless corpuscles in enormously disproportionate numbers. 'We shall afterwards see that there is a kind of blood - leticocytluemic blood - which. ap-proximatos to pus in these its essential characters.
That which distinguishes the process of repair from the forma-tive process in the two cysts, and in all tumours whatsoever, is that the former is self-limited ; after a titue skin forms on the surface of the granulations, and the lower layers of cells pass into the resting condition of fibrous tissue. Each of these adaptations has now to be described.
Formation, of Sk.in on. a Granulating Surface. - The new skin appears as a delicate bluish frill extending gradually over the raw surface from the margin of the old skin. Nothing is more natural, therefore, than to suppose that it is a continuous growth from the cells of the rete mucosuni of the old skin ; and, according. to the embryological dogma of an impassable gulf between the epiblast, inesoblast, and hypoblast for histogenetic purposes, the 1101V epidermis can have no other source than proliferation from corre-sponding cells of the old. But, dogma apart, there is a radical difference of opinion as to the origin of the epidermic or epithelial cells on the surface of granulations. Notwithstanding the fact that the IleNV epithelium springs up alongside the old, it has appeared to many observers with the microscope that it was derived, not from subdivision of the latter, but from the granulation-cells becoming fiat and otherwise adapted to surface purposes. In considering these difficulties let us, as before, seek analogies among othor formative incidents of mature life. In the first place it should be mentioned that the new skin may be peculiar. The accompanying figure (fig. 11) is drawn from a section through the sear of an ulcer of the leg which had broken out and healed re-peatedly-. The peculiarity is that the epithelial cells are every-where a narrow belt which bends down and encloses the terminal vessels as in a loop ; in other words, the surface vessels are driven through the midst of the rete mucosum of the new skin. For an analogy to this epitheliation of granulation-tissue we may take the case of' the cyst already referred to ; it was covered in part with a thick layer of epidermic scales. The origin of these in the cyst is not difficult to trace ; they are the granulation-cells enlarged, with two, three, or four nuclei, and with a, more homogeneous protoplasm. The surface-layer is in fact largely made up of multinuclear blocks, some of which become excavated in their in-terior, while their nucleated peri-phery forms a narrow belt of surface-cells with a descending loop enclos-ing a space, in which collections of blood-corpuscles may sometimes be seen (fig. 12). If we imagine the plexus of vessels ramifying on the granulating surface to form com-munications with these excavations in the multinuclear blocks, wc should be able to understand how it is that they are driven through the rete mucosum of a scar, as in fig. 11.
Giant-cells in Repair. - These multinuclear blocks are the so called giaml-cells. Their occurrence . in fungous granulations was de-sdribed by Billroth (op. cit., p. 32) in 1856, he having previously seen them in the granulations of bone and taken them - to be elements "necessary for the new formation of vessels in osteophyt-es or ill cal-lus." The accompanying figure (fig. 13) shows several examples of them from the granulations of a slow-healing stump. Precisely the same forms occur in the wall of the cyst whose structure has been already referred to in order to illustrate tile granulations of repair.
from the subdivision of a single nucleus within a growing cell of the inner muscular coat ; and their place in the placental pro-cess is as dear as their histogenesis. They enter into the formation of the blood-sinuses of the deeper parts of the organ, some-thnes forming a consider-able part of the wall of a vessel by being excavated in their interior (the nuclei being driven to the side), at other times forming one side of a blood-cliamiel, - a corresponding multinuc-/ear block forming the other, and the lumen of the vessel being the space between them. They represent a some-what feebler continuation of those vaso-formative processes in the placenta which we have already used as the analogy for the pro-duction of the new vessels of granulations. That their function and significance in granulations is not wholly vaso-formative will appear from the fact of their co-operating to build up the surface epithel i um.
Conversion of Geanulation- tissue into Scar- tissue. - The skin S of a sear is never perfect ; it is always thin, wanting the descend- t ing processes and papillre of the natural skin, and wanting also the hair-follicles, hairs, sebaceous glands, and sweat-glands. Its blood-vessels never become the orderly capillary loops of the original type ; they remain for a time as an extensive plexus of large vessels close to the surface, giving a recent scar its livid ap-pearance; afterwards the channels of the vessels become narrower, and many of them quite occluded ; and the scar has in the end a somewhat blanched appearance, which continues even when the surrounding skin is thrown into a state of ruddy glow. The underlying tissue, however, gradually acquires more of the natural type. If a section be made through an old scar it will be seen that the subcutaneous tissue is fibrillar and fibrous, with more or less of fat-cells. In the figure (fig. 15), drawn from a section through the scar of an ulcer of the leg which had broken ont and healed. more than once, the tissue is composed of parallel wavy fibres, with spindle-cells between them at regular intervals, the cells having (as a characteristic of sear-tissue after repeated heal-ing) brown pigment-grains in their substance. The successive changes which have led up to this horizontal fibrillation are not difficult to follow. While the ascending vessels acqnire more and more of elongated cells on their walls, the granulation-cells in the intervals between them become extended horizontally or obliqnely (sec fig. 7), the spindle-cells among the fibrillar bundles in the figure being the surviving representatives of them. The change of the spherical cells into spindle-cells, which precedes the fibrillation, takes place first in the deepest or oldest stratum of the granula-tion-tissue, and it appears to be accompanied by a certain dragging flown or obliquity of the vessels running to the surface. There is always a considerable thickness of spindle-cells parallel to the vessels, so that these, together with the horizontal tracts between the vessels, make np a kind of warp and woof. Mit as the sear-tissue matures the horizontal bands come to overshadow the vertical or oblique. The fibrillation takes place, as it does in ordinary growth, in an intercellular or perinuclear homogeneous protoplasm, which becomes more extensive as the embryonic or purely cellular character of the granulation-tissue fades. One of the most striking facts in this development of embryonic tissue into mature tissue in the adult is its shrinkage, corresponding to the well-known con-traction of the area of a healing surface.
Repair of a Broken llone. - The reparative process in bone is B much simpler and it may be said to be much easier than in tlie healing of a stump. The bones retain even to old age the materials out of which IICW bone may be produced ; these are the somewhat embryonic membrane covering the bone, or the periosteum, and the marrow. During the growing period these two tissues retain pronounced embryonic characters, and at - all times they take on a formative action. readily. However unlikely an object, then, a bone may seem for repair, it has within and around it the materials for a tolerably direct renewal of OSACOIIS substance. The most orderly or intelligible form of the re-parative process is that seen in animals. A long bone, such as the tibia or shin-bone, after having been broken and carefully set, presents an appearance such as is drawn in the figure (tig.16, a). Opposite the line of fracture there is a fusiform thickening all round the bone, which is bulky and carti-laginous for a time, and afterwards becomes greatly reduced in extent, and, at the same time, osseous in its structure. It is called the callus. It will be convenient to de-scribe the details of this process of repair from actual specimens of the tibia of a young frog which was found undergoing repair after fracture. The tibia, when cleared of the muscles, was found to have spimIledike enlargement about its middle of the size and shape of an oat (fig. 16, b) and of a whitish colour. It was easily cut up into sections passing through its whole length as well as through the projecting ends of the spindle representing the normal shaft of the bone (lig. 17). The bulk of this frisiform enlargement is made up of cartilage developed between the upraised periosteum and the dense substance of the bone. But there is another and independ-ent new-formed mass projecting from the canal of the bone, and clearly marked off from the wide extent of cartilage around it, - this is the direct osseous formation from the marrow. The cartilage has been pro-duced from the periosteum, each spindle-cell of the latter altering its form and developing a disproportionate amount of cell-substance, which becomes the hyaline matrix of the cartilage, while the nucleus or the original cell, generally excavated or reduced to a crescentic shape, remains as the cartilage-cell. From this cartilage, again, bone is formed very much as it is formed from the central rod of cartilage in the fetal bone, and it also resembles the latter in being formed only to he reabsorbed. In these preparations from the frog, nar-row spicithe of bone may be seen start-ing froin the thin end of the spindle and spreading over the surface of' the cartilaginous cal-lus. In the deeper strata of the latter, and still at the thin end of the. spindle, the cartilage-cells group themselves round the walls of alveolar spaces, as in the ossification of epiphysial carti-lage, and that is, doubtless the pro-` cess which extends throughout the whole mass of car-tilage. -.Meanwhile there has arisen a fungus-like protru-sion of new bone from the medullary canal of the bone ; it lines the inner walls of the medullary cavity for a short distance up from the line of fracture, and projects for a greater distance into the midst of the cartilaginous callus. This centre of ossification is intimately connected with the blood-vessels of the marrow ; they form the framework of the osseous growth, the embryonic marrow-cells (themselves the lineal descendants of cartilage-cells) becoming the osteoblasts or future bone-corpuscles. The whole of the IICW growth of bone is ultimately moulded into a more coinpact form ; but the seat of an old fracture will always retain a certain roughness of exterior, and a certain want of regularity in its Haversian systems.
The repair of bone in man is not altogether the same as in animals ; the ensheathing cartilage is not usually- found except in broken ribs, and the uniting osseous substance corresponds niostly to that part of the I/CW bone (in the preparation from the frog) which issues from the medullary cavity in association with the blood-vessels of the marrow. The callus in man is accordingly said to be chiefly " intermediate " or between the broken ends, and partly also " interior," or extending into the medullary canal ; and it is naturally permanent and not subject to removal like the " ensheathing " callus developed from cartilage. But the sources of new bone in man depend upon the amount of displacement of the broken ends ; if the displacement be very considerable, the connective tissues around may be drawn upon for bone-forming materials, their cells becoming embryonic in form and nitimately osteoblasts. Comparing the repair of a bone with the repair of soft parts, the former is much more direct ; the osteoblastie tendency or memory is strong in the tissues within and around a bone, above all in the periosteum and in the young or red marrow ; and true osseous -union is readily effected except in such fractures as the Deck of' the thigh-bone and the knee-cap, where the union is often merely ligamentous or fibrous. In the "green-stick " fractures of children the periosteum is still a succulent layer engaged in the natural growth of the bones, and there is reason to suppose that it is the chief source of whatever reparative materials may be needed.
Repair of Nertvs and Museles. - When a nerve, such as the ulnar, is divided by a cut near the wrist, sensibility is lost over the area of skin to which the nerve is distributed, and, under ordinary cir-cumstances, it is restored in about three weeks. The severed ends of the nerve are joined by- a baud of tissue, which has been proved by examination of it at various stages of the reparative process in animals to be at first composed of embryonic spindle-cells arranged in the line of the nerve-bundles (fig. 18) ; these cells are derived from the nuclei of the nemilenima, they pass through the ori-ginal embryonic phasos, and ultimately become more or less perfect nerve-tubes : filling the gap in the divided nerve, - a gap which inay be a quarter or half an inch in length. In muscle, also, a corresponding process is described ; but the repair of a ruptured muscle such as the rectus extensor of the thigh is commonly fibrous only, and the gap can be felt even throngh the skin.'