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the defibrinated blood is allowed to stand, a voluntary separation at once takes place, the whole of the bloodcorpuscles, red and colourless, gradually sinking to the bottom of the vessel, and there forming a double sediment, a lower red stratum, covered by an upper, white and puriform one. This is explained by the difference in the specific gravity of the two kinds of corpuscles and the time they take to sink (p. 154). In this way too we are enabled very readily to distinguish leukaemic from chylous (lipaemic) blood in which a milky appearance of the liquor sanguinis is produced by the admixture of fat, for, if the fibrine be removed, after some time there forms not a white sediment, but a cream-like layer on the surface.
In the histories of all the known cases of leukaemia we only find it once as yet recorded that the patient, after he had been for some time the subject of medical treatment, left the hospital considerably improved in health. In all the other cases the result was death. I do not wish by any means to infer from this that the disease in question is absolutely incurable; I hope on the contrary that for it too remedies will at length be discovered; but it is certainly a very important fact that we have in it, much, as in the progressive atrophy of muscles, to deal with conditions, which, when abandoned to themselves, or subjected to any one of the hitherto known methods of treatment, continually grow worse and ultimately lead to death. These cases possess in addition the remarkable peculiarity that, usually towards the close of life, a genuine hemorrhagic diathesis is developed and haemorrhages ensue, which occur with especial frequency in the nasal cavity (under the form of exhausting epistaxis) but may also, under certain circumstances, take place in other parts of the body, as for example on a very large scale in the, form of apoplectic clots in the brain, or of melaena in the intestinal canal.
Now upon investigating whence this curious change in
the blood takes its origin, we find in the great majority of cases that it is a certain, definite organ which presents itself over and over again with convincing constancy as the one essentially diseased, an organ which frequently, even at the outset of the malady, forms the chief object of the complaints and distress of the patients, namely the spleen. In addition, a number of lymphatic glands are very frequently diseased, but the affection of the spleen stands in the foreground. Only in a few cases have I found the change in the spleen the less and that in the lymphatic glands the more prominent, and in these, matters had proceeded to such a pitch, that lymphatic glands at other times scarcely observable, had developed themselves into lumps the size of walnuts, and that indeed in some few places there appeared to be scarcely anything else than glandular substance. Of the glands which lie between the inguinal and lumbar glands we are wont to hear but little, nor have they indeed even a suitable name. Some of them lie in the course of the iliac vessels, and some in the real pelvis. But in two of these cases of leukaemia I found them so enlarged that the whole cavity of the pelvis proper was, as it were, stuffed full of glandular substance, between which the rectum and the bladder only just dipped in.
I have therefore distinguished two forms of leukaemia, namely the ordinary splenic, and the lymphatic, form, which are certainly not unfrequently combined. The distinction rests not only upon the circumstance, that in the one case the spleen, in the other the lymphatic glands, constitute the starting point of the disease, but also upon the fact that tlfc characteristic morphological elements which are found in the blood are not precisely similar. Whilst namely in the splenic forms these elements are generally comparatively large and perfectly developed cells with one or more nuclei, and in many cases bear a particularly great resemblance to the
HYPEItlNOSIS, LEUCOCYTOSIS AND LEUKEMIA. 171
cells of the spleen, we notice in the well-marked lymphatic forms that the cells are small, the nuclei large in proportion and single, usually sharply defined, with dark outlines and somewhat granular, whilst the cell-wall is frequently in such close apposition to them that an interval can scarcely be demonstrated. In many instances it looks as if perfectly free nuclei were contained in the blood. In these (the lymphatic) cases, therefore, it seems that the enlargement of the glands alone, which is accompanied in its progress by a real increase in the number of their elements (hyperplasia), also conveys a larger number of cellular elements into the lymph and through this into the blood, and that, just in proportion to the predominance of these elements, the formation of the red cells suffers obstruction. This is in a few words the history of these processes. Leukaemia is thus a sort of permanent, progressive leucocytosis, whilst this on the other hand in its simple forms constitutes a transitory process, connected with fluctuating conditions in certain organs.
You see therefore that there are at least three different conditions here, bordering one upon the other, hyperinosis, leucocytosis and leukaemia, between which and the lymphatic fluids there exists an intimate connection. The one series, that namely which is distinguished by an increase in the quantity of fibrine, is rather to be referred to the accidental condition of the organs from which the lymphatic fluids are derived, whilst those states which are induced by an increase in the number of cellular elements are rather regulated by the condition of the glands through which these fluids have flowed. These facts can hardly, I think, be interpreted in any other manner than by supposing that the spleen and lymphatic glands are really intimately concerned in the development of the blood. This has become still more probable since we have succeeded in obtaining chemical evidence also in support of it. Herr Scherer upon two occasions examined lcukaemic blood which I had submitted to him, in order to compare it with the matters he had discovered in the spleen, and the result was that hypoxanthine, leucine, uric, lactic, and formic, acid, were found there. In one case of leukaemia a liver which I had kept for several days, became entirely covered with granules of tyrosine; in another, leucine and tyrosine crystallized in large masses out of the contents of the intestines. In short, everything points to an increased action in the spleen, which normally contains these substances in considerable quantity.
A good many years elapsed (after 1845) during which I found myself pretty nearly alone in my views. It has only been by degrees and indeed, as I am sorry to be obliged to confess, in consequence rather of physiological than pathological considerations, that people have come round to these ideas of mine, and only gradually have their minds proved accessible to the notion, that in the ordinary course of things the lymphatic glands and the spleen are really immediately concerned in the production of the formed elements of the blood; and that in particular the corpuscular constituents of this fluid are really descendants of the cellular bodies of the lymphatic glands and the spleen which have been set free in their interior and conveyed into the current of the blood. And let this serve as an introduction to the consideration of the question of the origin of the blood-corpuscles themselves.
You will probably recollect, gentlemen, from the time of your studies, that the lymphatic glands used to be regarded as coils of lymphatic vessels. The afferent lymphatics may, as is well known, even with the naked eye be seen breaking up into smaller branches, disappearing within the glands, and finally again emerging from them. From the results of the mercurial injections which even in the last century were made with such great care, the only inference to
STRUCTURE OF LYMPIIATIC GLANDS. 173
be drawn appeared to be, that the afferent lymphatic vessel formed a number of convolutions, which interlaced in various ways and were finally continued into the efferent vessel, so that the gland was composed of nothing else than the thickly crowded coils of the afferent vessels. The whole attention of modern histologists has been directed to the task of confirming this tortuous transit of the lymphatic vessels through the gland, but after many years of labour spent in vain, the attempt was at length abandoned.
At the present moment there is, I should suppose, scarcely an histologist who believes in the perfect continuity of the lymphatic vessels throughout the gland, but Kolliker's view is generally adopted, that the lymphatic glands interrupt the current of the lymph, the afferent vessel resolving itself into the parenchyma of the gland and reconstituting itself out of it. This condition we cannot well compare with anything else than a kind of filtering apparatus, something like our ordinary sand or charcoal filters.
When a gland is cut across, a structure is frequently brought to view resembling that of a kidney. At those points where the afferent vessels break up, a firmer substance is seen to he, half surrounded by which a kind of hilus marks the spot at which the lymphatic vessels again forsake the gland. Here there is found a reticular tissue with an often distinctly areolar or cavernous structure, into which, besides the efferent lymphatic vessels, blood-vessels also enter on their way into the proper substance of the gland. Kolliker has accordingly distinguished a cortical and a medullary substance; but the so-called medullary substance scarcely retains the character of glandular tissue. This is found chiefly in the cortical substance which is of greater or less thickness, and it is therefore best to call the medullary substance simply the hilus, since afferent and efferent vessels lie there in close contact, just as in the hilus of the kidneys the ureters and veins emerge, whilst the