Part 12

The nucleus stains very deeply with all dyes; the protoplasm possesses a strong attraction for most acid stains, and is unmistakeably characterised by the presence of a dense neutrophil granulation. The reaction of the protoplasm is alkaline, to a less degree however than in the lymphocytes. No free glycogen is contained in the polynuclear cells as a rule; nevertheless in certain diseases cells are always found which give a marked iodine reaction. In this manner the appearance of cells containing glycogen in diabetes was first proved. (Ehrlich, Gabritschewsky, Livierato.) The iodine reaction in the white blood corpuscles is also seen in severe contusions and fractures, in pneumonias, in rapidly progressing phlegmata from streptococcus and staphylococcus, after protracted narcosis (Goldberger and Weiss).

Ehrlich explains the appearance of glycogen as follows. The glycogen is not present in the cell as such, but in the form of a compound, which does not stain with iodine. This compound readily splits off glycogen, which then gives the iodine reaction.

We cannot regard the perinuclear green granules, described by Neusser in the polynuclear cells, as pre-existing. (See p. 42.)

The number of polynuclear leucocytes in the blood of the healthy adult amounts to about 70-72%, of the total white corpuscles. (Einhorn.)

5. =The eosinophil cells.= These are characterised by a coarse, round granulation, staining deeply with acid dyes, and similar in other respects to the polynuclear neutrophils. With faint staining, a thin peripheral layer of the eosinophil granule is seen more deeply stained than the interior. The nucleus as a rule is not so deeply stained as in the polynuclear neutrophil, but otherwise in its general shape is completely similar. Both forms have in common a considerable contractility, which renders possible their emigration from the vessels, and their appearance in exudations and in pus. The size of the eosinophils frequently exceeds that of the neutrophils. Their number is normally about 2-4% of the white cells.

6. The mast cells. These are present, though very sparingly, in every normal blood; 0.5% is their maximum number in health.

Their intensely basophil granulation, of very irregular size and unequal distribution, must specially be mentioned. The granulation possesses the further peculiarity, in that with the majority of basic dyes it stains, not in the pure colour of the dye, but metachromatically--most deeply with thionin. As Dr Morgenroth found, the deviation from the colour of the dye is still more marked with Kresyl-violet-R (Mülheim manufactory), when the granules stain almost a pure brown.

The staining power of the nuclei is very small, and it is therefore hard to make out the shape of the nucleus without the use of difficult methods. In triacid preparations the granulation is unstained, and the mast cells appear as clear, polynuclear cells, free from granules.

* * * * *

So much for the colourless cells in the blood of the normal adult.

In pathological cases, not only do the forms so far mentioned occur in altered numbers, but abnormal cells also make their appearance. To these belong:

1. =Mononuclear cells with neutrophil granulation.= ("=Myelocytes=," Ehrlich.) Generally they are bulky, with a relatively large, faintly staining nucleus, often fairly centrally placed, and equally surrounded by protoplasm on all sides. A fundamental distinction from the large mononuclear cells lies in the fact that the protoplasm exhibits a more or less numerous neutrophil granulation. Besides the larger myelocytes, much smaller forms, approximating to the size of the erythrocytes are also found. All transitions between these two stages are likewise met with. In contradistinction to the polynuclear neutrophil elements, these mononuclear forms shew no amoeboid movement on the warm stage. They form a constant characteristic of myelogenic leukæmia, and in these cases generally occur in large numbers.

Reinbach has found them in a case of lymphosarcoma with metastases in the bone-marrow. A. Lazarus observed their transitory occurrence in moderate number in a severe posthæmorrhagic anæmia. M. Beck observed them in the blood of a patient with severe mercury poisoning. They are also frequently found in children's diseases, especially in anæmia pseudoleukæmica infantum. K. Elze established their presence in a boy of 15 months, suffering from a slowly progressing tuberculosis of the lymphatic glands.

The appearance of myelocytes in infectious diseases is particularly interesting. Rieder had previously demonstrated that myelocytes may be present in acute inflammatory leucocytoses; and recently a thorough work by C. S. Engel has appeared upon the occurrence of myelocytes in diphtheria. Engel discovered the interesting fact, that myelocytes are often to be found in children suffering from diphtheria, and further made the important observation that a high percentage of myelocytes (3.6-16.4% of the white elements) only occurs in severe cases, and points to an unfavourable prognosis. Myelocytes are also present in mild cases, though not constantly and in much smaller number. Türk has recently undertaken a very exact and thorough analysis of their occurrence in infectious diseases, in the course of which he accurately tabulated the white corpuscles in a large number of cases. The results he obtained in pneumonia are especially characteristic, for he found at the commencement of the disease that myelocytes are not seen at all or only very scantily: and it is only at the time of the crisis, or directly afterwards, that they become specially numerous. In isolated cases the increase at this time was very considerable; and in one case amounted almost to 12% of all neutrophil cells.

2. Mononuclear eosinophil cells ("=eosinophil myelocytes="). H. F. Müller was the first to point out their importance. They constitute the eosinophil analogue of the previous group, and are much larger than the polynuclear eosinophils; medium and small sized examples are often found in leukæmia. Eosinophil myelocytes are almost constantly present in myelogenous leukæmia and in anæmia pseudolymphatica infantum. Apart from these two diseases they are very rarely found; Mendel saw them for example in a case of myxoedema, Türk quite exceptionally in some infectious diseases.

3. =Small neutrophil pseudolymphocytes.= They are about as large as the small lymphocytes, possess a rounded deeply stained nucleus, and a small shell of protoplasm studded with a neutrophil granulation. The relatively deep stain of the nucleus and the small share of the protoplasm in the total cell body prevent confusion with the small forms of myelocytes, which never reach such small dimensions. The neutrophil pseudolymphocytes are exceedingly infrequent, and represent products of division of the polynuclear cells; they were first described by Ehrlich in a case of hemorrhagic small-pox. The process of division goes on in the blood in such a manner that the nuclear rod first divides into two to four single nuclei, and then the whole cell splits up into as many fragments. These cells occur also in fresh pleuritic exudations. After a time the nucleus of these cells becomes free, and the little masses of protoplasm thus cut off are taken up mostly by the spleen substance. The free nucleus likewise shares in the destruction. It is of the greatest importance that these cells, which up to the present have not elsewhere been described, should receive more attention. They must be of significance, in particular for the question of transitory hyperleucocytosis, which is by some referred to a destruction, by others to an altered localisation of the white blood corpuscles.

4. "=Stimulation forms=" were first described by Türk, and are mononuclear non-granulated cells. They possess a protoplasm staining with various degrees of intensity, but in any case giving with triacid solution an extraordinarily deep dark-brown, and further a round simple nucleus often eccentrically situated, stained a moderately deep bluish-green, with however a distinct chromatin network. The smallest forms stand between the lymphocytes and the large mononuclear leucocytes, but approach the first named as a whole in their size and general appearance. According to Türk's investigations, these cells often occur simultaneously with, and under the same conditions as the myelocytes. Their importance cannot at present be accurately gauged. Possibly they form an early stage of development of the nucleated red blood corpuscles, as the deeply staining and homogeneous protoplasm seems to indicate.

With the description of these abnormal forms of white corpuscles all occurring forms are by no means exhausted. We are here excepting completely the variations in size which particularly affect the polynuclear and eosinophil cells, and which lead to dwarf and giant forms of them. For however considerable the difference in size, these cells always possess characteristics sufficient for an exact diagnosis. But besides these, isolated cells of an especially large kind are found particularly in leukæmic blood, and concerning their importance and relationship we are up to the present in the dark.

FOOTNOTES:

In enumerating the blood corpuscles, 2 and 3 may be counted separately or in one group.

The assumption of Czerny, that the cells which react to iodine emigrate from suppurating foci, is without foundation. A simple investigation of freshly inflamed tissue is sufficient to show that the cells which have wandered from the blood stream soon contain glycogen.

Kanthack described this group as "finely granular oxyphil" cells. Their granules stain red in eosine and in eosine-methylene blue solutions, but the colour is different from that of the true eosinophil cells, and much less intense. In the latter mixture they stain really with the methylene blue salt of eosine. Their true nature is shown by their behaviour with the triacid solution.

II. ON THE PLACES OF ORIGIN OF THE WHITE BLOOD CORPUSCLES.

For the comprehension of the histology of the blood as a whole, it is of great importance to obtain an exact knowledge how and to what extent the three organs, which are undoubtedly very closely connected with the blood, lymphatic glands, bone-marrow, and spleen, contribute to its formation. The most direct way of deciding the question experimentally by excision of the organs in question, is unfortunately only available for the spleen. The part played by the lymphatic glands and bone-marrow, whose exclusion in toto is not possible, must mainly be determined by anatomical and clinical considerations. But only by a careful combination of experiments on animals, of anatomical investigations, and especially, of clinical observations on a large scale, can light be thrown on these very difficult questions. It cannot be emphasised sufficiently how important it is that everyone engaging in hæmatological work should first of all collect a large series of general observations; otherwise errors are bound to occur. For instance, the endeavour is often made to compensate the lack of personal experience by careful literary studies; but in this way the histology of the blood falls into a vicious circle, of which the new phase of blood histology affords many examples. And it is characteristic of this kind of work that from the investigation of a single rare case, most far-reaching conclusions on the general pathology of the blood are at once drawn; e.g. Troje's paper, in which having failed to recognise the lymphocytic character of a case of leukæmia, and believing therefore that he had to do with a myelogenous leukæmia, the author denied and completely reversed all that had been previously established about this disease. It is equally hard to avoid errors if one confines oneself exclusively to animal experiments, without supplementing these by clinical experience, as is shewn by the numerous papers of Uskoff. Not the anatomist, not the physiologist, but only the clinician is in the position to discuss these problems.

In the introduction to this chapter we have already alluded to the striking retrograde movement in hæmatology at the present time, brought about by the view that the white corpuscles as a whole are derived from the lymphocytes. If we disregard the embryological investigations on this point (Saxer), anatomists, physiologists, and clinicians alike have taken up a similar point of view. Among anatomical papers we may refer to those of Gulland, according to whom all varieties of leucocytes are but different stages of development of one and the same element. He distinguishes hyaline, acidophil and basophil cells, and derives all from the lymphocytes. Arnold advocates similar views, though in a negative form. He says that a distinction between so-called lymphocytes and the leucocytes with polymorphous nuclei, on the grounds of the form of the cell and nature of the nucleus, is not possible at the present time. Neither is a classification based on the granules admissible, since the same granules occur in different cells, and different granules in the same cell. The work of Gulland and Arnold takes into consideration the differential staining of the granules in various ways. In spite of their facts we disagree with their conclusions; and we shall therefore have to analyse them in the special description of the granulated cells and granules.

Recently (since 1889) Uskoff has in particular published experimental work in this province of hæmatology. This has led him to see in the white blood corpuscles the developmental series of one kind of cell, and to distinguish in it, three stages: (1) "young cells," which correspond to our lymphocytes; (2) "ripe cells" (globules mûrs), large cells with fairly large and irregularly shaped nucleus, which are therefore our large mononuclear and transitional forms; (3) "old cells" (globules vieux), which represent our polynuclear cells. The eosinophil cells are completely excluded from this classification. Amongst clinicians A. Fränkel has recently gone in the same direction, and on the grounds of his experience in acute leukæmias has supported the view of Uskoff, that the lymphocytes are to be regarded as young cells, and early stages of the other leucocytes. But few authors (for instance C. S. Engel, Ribbert) have raised a protest to this mixing of all cell forms of the blood, and have held to the old classification of Ehrlich. But as it is emphatically taught in numerous medical works that all these cells are closely related, the grounds for sharply separating the lymphocytes from the bone-marrow group may here be shortly summarised, and stress laid on the great importance which this apparently purely theoretical question has for clinical observation. We shall come to most important conclusions upon this point when we consider more closely the share which the various regions of the hæmatopoietic system take in the formation of the blood, and especially of the colourless elements.

The question whether the ~spleen~ produces white blood corpuscles has played a large part from the earliest times of hæmatology.

Endeavours were first made to investigate the participation of the spleen in the formation of the white blood corpuscles by counting the white corpuscles in the afferent and efferent vessels of the spleen. It was thought that the blood-forming power of the spleen was proved by the larger number of corpuscles in the vein as compared with the artery. The results of these enumerations however are very varying; the investigators who found a relative increase in the vein are opposed by other investigators equally reliable; and with the experience of the present day one would not lay any value on these experiments.