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the bone-corpuscle accomplish its peculiar destinies. If, for example, the bone is by any cause impelled to enter upon new transformations, one bone-corpuscle after another with its territory experiences the change. At the border of necrosed portions of bone, when the line of demarcation forms, we may distinctly observe, that the surface of the bone, when viewed along the edge, becomes marked with excavations, the extent of which corresponds to the original cells. Upon the surface vacuities are observable, which in some instances run together and form holes. The bonecorpuscle which formerly occupied the site of the hole has, in proportion as it underwent transformation itself, also determined the surrounding parts to enter upon the change. These are the processes, without the aid of which it is impossible to comprehend the history of caries. For the whole essence of caries consists in this: the bone breaks up into its territories, the individual corpuscles undergo new developmental changes (granulation, suppuration), and remnants1 composed of the oldest basis-substance remain in the form of small, thin shreds in the midst of the soft substance. I traced this out again only to-day in a stump, in which, a fortnight after amputation, periostitis with slight suppuration and incipient peripheral caries was found to exist. When in such a case the thickened periosteum is stripped off, we see, at the moment it quits the surface and the vessels are drawn out from the cortex of the bone, not, as in normal bone, mere threads, but little plugs, thicker masses of substance; and if they have been entirely drawn out, there remains a disproportionately large hole, much more extensive than it would be under normal circumstances. On examining one of these plugs you will find that around the vessel a certain quantity of soft tissue lies, the cellular elements of which are in a state of fatty degeneration. At the spot where the vessel has been drawn out, the surface does not appear even, as in normal bone, but rough and porous, and when placed under the microscope, you remark those excavations, those peculiar holes, which correspond to the liquefying bone-territories. If it be asked therefore in what way bone becomes porous in the early stage of caries, it may be said that the porosity is certainly not due to the formation of exudations, seeing that for these there is no room, inasmuch as the vessels within the medullary canals (Figs. 32, 33) are in immediate contact with the osseous tissue. On the contrary, the substance of the bone in the cellular territories liquefies, vacuities form, which are at first filled with a soft substance, composed of a slightly streaky connective tissue with fattily degenerated cells. If round about a medullary canal the territory of one bone-corpuscle after another liquefies, you will after a time find the canal bounded on all sides by a lacunar structure. In the middle of it the vessel conveying the blood still remains, but the substance round about is not bone or exudation, but degenerate tissue. The whole process is a degenerative ostitis, in which the osseous tissue changes its structure, loses its chemical and morphological characters, and so becomes a soft tissue which no longer contains lime. The tissue, which fills the resulting vacuity in the bone, may vary extremely according to circumstances, consisting in one case of a fattily degenerating and disintegrating substance (the bone-corpuscles GRANULATIONS, PUS. 421

1 In ossification (in cartilage) there is a portion of the original intercellular substance of the cartilage—that, namely, which lies between the large groups of cartilage-cells (secondary cells—Tochterzellen)—which, though it belongs to the groups as wholes, yet when these, in the course of ossification, are transformed into a number of isolated bone-cells, becomes, comparatively speaking, almost entirely independent of these cells individually (which have their own immediate intercellular substance to attend to, and from most of which it must be separated by a considerable interval), and therefore escapes the changes which befall them. It is this portion (well shewn in Fig. 126, where it is represented by the trabecular separating the medullary spaces m), which remains behind in caries, whilst the secondary intercellular substance perishes. In other processes, however, which run a more chronic course (in cancer, for example), everything is destroyed.—Based upon MS. notes by the Author.

perishing), and in another of a substance rich in cells and containing numerous young cells; this latter is formed by the division and proliferation of the bone-corpuscles, and the newly produced substance is very analogous to marrow. Under certain circumstances this substance may grow to such an extent, that—if we again borrow our illustration from the surface of the bone, where a vessel sinks in—the young medullary matter sprouts out by the side of the vessel, and appears as a little knob, filling one of the pits in the surface. This we call a granulation.

When we examine granulations for the purpose of comparing them with medullary tissue, we find that no two descriptions of tissue more closely correspond. The marrow of the bones of a new-born-infant could at any time, both chemically and microscopically, be passed off as a granulation. Granulations are nothing more than a young, soft, mucous tissue, analogous to marrow. There is an inflammatory osteoporosis, which, as has been correctly stated, merely depends upon an increased production of medullary spaces, so that the process which is quite normal in the interior of a medullary cavity, is met with also more externally in the compact cortex. It (the osteoporosis) is distinguished from granulating peripheral caries only by its seat. If you go a step farther and suppose the cells, which in osteoporosis are present in moderately large numbers, to become more and more abundant, whilst the intercellular substance constantly becomes softer and diminishes in quantity, we have pus. The pus is here no special product, separable from the other products of proliferation and formation; it is certainly not identical with the preexisting tissues, but its origin can be directly traced back to the elements of the pre-existing tissue. It is not produced by any special act, by any creation de novo, but its development proceeds from generation to generation in a perfectly regular and legitimate manner.

We have therefore before us a whole series of transformations; the bone first produced and proceeding from cartilage may undergo a transformation into marrow, then into granulation-tissue, and finally into nearly pure pus. The transitions are here so gradual, that the pus which is in immediate contact with the granulations, constitutes, as is well known, a more mucous, stringy, and tenacious matter, which really contains mucin like the granulation-tissue, and only when we proceed farther outwards, exhibits the properties of completely developed pus. The perfect pus of the surface gradually passes, as we descend, into crude pus, the mucous, tenacious, immature pus of the deeper layers, and what we call maturation depends simply upon the gradual conversion of the mucous intercellular substance of the originally tenacious pus, which is allied in structure to granulations, into the albuminous intercellular substance of pure pus. The mucus dissolves and the creamy fluid is produced. The maturation is therefore essentially a softening of the intercellular substance. So direct is the connection which subsists between development, and retrograde metamorphosis, physiological and pathological conditions.

In just the same manner that the cartilage-cell may become a bone-corpuscle, the marrow-cell also may become a bone-corpuscle. In the medullary spaces of bone those marrow-cells which are situated at the circumference, generally assume at a later period a more oblong form, and take a direction parallel to the internal surface of the medullary spaces, and the medullary tissue in this situation has a more fibrous appearance and has indeed been regarded as a medullary membrane, but it should not be separated from the marrow in the centre of the spaces, and only constitutes the most compact layer of the medullary tissue. Now as soon as osseous tissue is about to form, the nature of the basis-substance alters. It becomes firmer, more


cartilaginous, and the individual cells appear to lie in largish cavities. Gradually they become jagged, from sending out little processes, and then nothing more is required than that calcareous salts should deposit themselves in the basissubstance—and the bone is complete. Thus here again also the osseous tissue is formed by a very direct transformation; and by the deposition of one such osteoid1 layer after another from the medulla, a compact substance is produced, like that of the cortex, which is always characterized by the lamellar deposition of osseous tissue in the previously existing medullary spaces. The original bone is always pumicestone-like, and porous; its porosities become filled by the subsequent development of osseous lamellae from the layers of the marrow, the process continuing until the vessel, which does not admit of ossification, alone remains.

Now with regard to the development of bones in thickness, the process is in itself much simpler, but it is also at the same time very much more difficult to see, because ossification here proceeds very rapidly, and the proliferating periosteal layer is so thin and delicate, that extremely great care is required in order to catch sight of it at all. Pathology furnishes us with an incomparably better opportunity for studying the process than physiology. For it is just the same whether the bone grows physiologically in thickness, or pathologically in consequence of periostitis; the difference is only one of quantity and time.

When fully developed, the periosteum consists for the most part of a very dense connective tissue, which contains an extremely large quantity of elastic fibres, and in which the vessels ramify, before they pass on into the cortex of the bone itself. Now when the growth of the bone in thickness commences, we see that the most internal, vascular

'Osteoid I call the tissue which, when it takes up calcareous salts, becomes bone,—in other words, soft, uncalcificd, osseous tissue.—From a MS. note by the Author.

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