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That the fibrine in the blood itself is produced by a transformation of the albumen, is a chemical theory, which has no other evidence in its favour than the fact that albumen and fibrine have a strong chemical resemblance, and that, on comparing the questionable formula for fibrine with the equally questionable one for albumen, it is very easy to imagine how, by the abstraction of a couple of atoms, the transition from albumen to fibrine might be effected. But our being able in this manner to deduce one of the formulae from the other does not afford the slightest proof that an analogous transformation occurs in the blood. It may possibly take place in the body, but even then it would at any rate be more probable that it was accomplished in the tissues, and that from them the fibrine was conveyed away into the blood by means of the lymph. This is however the more doubtful, because rational formulae for the chemical composition of albumen and fibrine have not yet been determined, and the incredibly high atomic numbers in the empirical formulae point to a very complex grouping of the atoms.

Let us therefore hold fast the well-ascertained fact that fibrine can only be made to exude upon any surface by the occurrence of some irritation, that is, local change, in addition to the disturbance in the circulation. This local change, however, is, as results from experiment, alone sufficient to cause the exudation of fibrine, even when no obstruction arises in the circulation. Such obstruction is not therefore in any way needed in order that the production of fibrine may commence at any given point. On the contrary, we see that the cause of the greatest differences in the nature of exudations is to be found in the special constitution of the irritated parts. On the simple application of an irritating substance to the surface of the skin, there arises, when the irritation, whether chemical or mechanical in its nature, is only slight in degree, a vesicle, a serous exudation. If the irritation is more violent, a LOCAL FORMATION OF FIBRINE. 165

liquid exudes, which in the vesicle appears quite fluid, but coagulates after its evacuation. If the fluid from a blister raised by a cantharides-plaster be received into a watch-glass and exposed to the air, a coagulum forms, shewing that there is fibrinogenous substance in the fluid. But we sometimes meet with conditions of the body, in which an external stimulus is sufficient for the production of blisters containing a fluid which directly coagulates. I had, last winter, a patient in my wards, whose feet had remained in a state of anaesthesia ever since they had been frozen, and I employed as a remedy, amongst other things, local baths containing aqua regia. After a certain number of these baths, blisters, which varied in diameter up to two inches, and were found, when opened, to be filled with large, jelly-like masses of coagulum, formed upon every occasion on the anaesthetic parts of the soles of the feet. In other persons probably ordinary blisters would have formed, containing a fluid, which would not have coagulated until after its evacuation. Such a difference manifestly depends upon a difference, not in the composition of the blood, but in the disposition of the part affected. The difference between that form of pleurisy, which from its very commencement furnishes coagulable and coagulating fluids, and that in which the exudation is coagulable, but not coagulating, certainly points to peculiarities in the local irritation.

I do not think therefore that we are entitled to conclude, that in a person who has an excess of fibrine in his blood, there is on that account also a greater tendency to fibrinous transudation; on the contrary, I should rather expect, that in a patient who produces at a certain point a large quantity of fibrine-forming substance, much of it would pass from that point into the lymph and finally into the blood. The exudation may therefore in such cases be regarded as the surplus of the fibrine formed in loco, for the removal of which the lymphatic circulation did not suffice. As long as the current of lymph does suffice, all the foreign matters which are formed in the irritated part, are conveyed into the blood; but, as soon as the local production becomes excessive, the products accumulate, and in addition to the hyperinosis, a local accumulation of fibrinous exudation will also take place. On account of the shortness of the time which is allotted to us, we cannot follow up this subject in its whole extent, but still I hope that you will at least completely grasp the fundamental idea which has guided me. Here too we have another example of that dependence of a dyscrasia upon a local disease to which I but a short time ago called your attention as being the most important result of all our investigations concerning the blood.

Now it is a very remarkable fact, and one which adds weight to this very view of mine, that it is very rarely that a considerable increase of fibrine takes place without a simultaneous increase in the colourless blood-corpuscles, and that therefore the two essential constituents which we find in the lymph, we again meet with in the blood. In every case of hyperinosis we may rely upon discovering an increase in the colourless corpuscles, or, in other words, every irritation of a part, which is abundantly provided with lymphatics, and freely connected with lymphatic glands, occasions also the introduction of large numbers of colourless cells (lymph-corpuscles) into the blood.

This fact is especially interesting, inasmuch as you will perceive from it, that not only organs richly provided with lymphatic vessels can occasion this increase, but that certain processes also are more calculated than others to lead to the introduction of considerable quantities of these elements into the blood, namely all those which are early conjoined with serious disease in the lymphatic system. If you compare' an erysipelatous, or a diffuse phlegmonous (according to Rust pseudo-erysipelatous), inflammation in its effects upon the blood with a simple superLEUCOCYTOSIS AND LEUKAEMIA. 1G7

ficial inflammation of the skin, such as occurs in the course of the ordinary acute exanthemata, or after traumatic or chemical irritation, you will at once see how great the difference is. Every erysipelatous or diffuse phlegmonous inflammation has the peculiarity of early affecting the lymphatic vessels and producing swellings in the lymphatic glands. In such a case we may feel assured that an increase in the number of the colourless corpuscles is taking place. Further we find the significant fact, that there are certain processes which simultaneously cause an increase of fibrine and colourless corpuscles, and others again which only occasion an increased production of the latter. To this latter category belong the whole series of simple diffuse inflammations of the skin, in which also no considerable formation of fibrine takes place in the diseased parts. On the other hand a number of conditions belong to it, which with regard to the quantity of fibrine may be designated as hypinotical, all the processes namely which belong to the typhoid class, and agree in producing considerable swelling now of one, and now of another, kind in the lymphatic glands, but do not produce any local exudation of fibrine. Thus typhoid fever causes these changes not only in the spleen, but also in the mesenteric glands.

The condition in which the increased proportion of colourless corpuscles in the blood appears to be dependent upon an affection of the lymphatic glands, I have designated by the name of Leucocytosis. Now you know that another matter has long been the subject of my studies, the affection named by me Leukcemia, and our next business must be to determine how far genuine leukaemia differs from these leucocytotical conditions. In the very first cases of leukaemia which came before me, a very essential property was discovered to exist; namely that there was no essential variation in the proportion of fibrine in the blood. Afterwards it was found out that the proportion of fibrine might, according to the particular circumstances of the case, be greater or less than, or the same as, usual, but that a continually augmenting increase of the colourless blood-corpuscles invariably took place; and that the coincidence of this increase with a diminution in the number of the coloured (red) corpuscles became more and more marked, so that as the final result a condition was attained, in which the number of the colourless corpuscles was almost equal to that of the red ones, and striking phenomena were displayed, even when the coarser modes of observation were employed. Whilst in ordinary blood we can seldom count more than one colourless corpuscle to about three hundred coloured ones, there are cases of leukaemia in which the increase of the colourless ones reaches such a height, that to every three red corpuscles there is one colourless one, or even two; or in which indeed the greater numbers are in favour of the colourless corpuscles.

In dead bodies the increase in the colourless corpuscles generally appears more considerable than it really is, from reasons which I but a short time ago pointed out to you (p. 152); for these corpuscles possess extraordinary adhesiveness and accumulate in considerable masses wherever there is a retardation in the stream of blood, so that in the dead body the greatest number is always found in the right heart. Once, before I left Berlin, this singular case occurred to me, that, when I punctured the right auricle, the physician who had treated the case cried out, astonished, "Why, there's an abscess there!" So like pus did'the blood appear. This puriform condition of the blood does not indeed pervade the entire circulating stream; the whole of the blood never looks like pus, because a comparatively large number of red corpuscles always continues to exist; still it sometimes happens that blood flowing from a vein even during life exhibits whitish streaks, and that, when the fibrine has been removed by stirring, and

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