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[12].
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.)[13]
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 amœboid 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 myxœdema, 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.
[11] In enumerating the blood corpuscles, 2 and 3 may be counted separately or in one group.
[12] 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.
[13] 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.
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.
We must emphasise the fact, established by later researches, that after extirpation of the spleen, an enlargement of various lymphatic glands occurs. The alterations of the thyroid, which have been observed by many authors, cannot be described as constant.
Further, the blood investigations which Mosler, Robin, Winogradow, Zersas and others have carried on in animals and man after removal of the spleen must here be mentioned. These have already proved that a leucocytosis occurs after some considerable time. Prof. Kurloff carried out detailed investigations in 1888 in Ehrlich's laboratory, and carefully studied the condition of the blood after extirpation of the spleen. As the work of Prof. Kurloff has so far only appeared in Russian, his important results may be here recorded more fully. For his researches, Kurloff employed the guinea-pig, as this animal by its peculiar blood is specially suited for this purpose.
In order to give a systematic account of the results of these important investigations, we must first shortly sketch the normal histology of the blood of the guinea-pig according to Kurloff.
In the blood of the healthy guinea-pig the following elements are found.
1. Polynuclear, with pseudoeosinophil granulation. This granulation, which Ehrlich had previously found in the rabbit, is easily distinguishable from the true eosinophil, since it is much finer, and stains quite differently in eosine-aurantia-nigrosin mixtures. One principal distinction between these two forms of cells lies in the fact that, according to Kurloff, this granulation is very easily dissolved by acid, but remains unchanged in alkaline solutions; doubtless an indication that the granulation consists of a basic body soluble with difficulty, which with acids forms soluble salts. The true eosinophil granulation remains, on the other hand, quite unchanged under these conditions.
These pseudoeosinophil, polynuclear cells, correspond functionally to the neutrophil polynuclear of man; their number amounts to 40-50% of the total white cells. The red bone-marrow is to be regarded as the place of origin of this kind of cell. It contains very many pseudoeosinophil cells, and indeed all stages are to be found in it, from the mononuclear cells bearing granules to the fully formed polynuclear.
2. The typical eosinophil leucocytes, which fully correspond to those found in man, and amount to about 10% of the number of the white.
3. The "nigrosinophil cells," as they are called by Kurloff. In their general appearance, in the size of the cell and the granulation, they completely correspond to the eosinophil cell. The only distinction between them consists in a chemical difference in the granulation. These cells stain in the colour of nigrosin in the aurantia-eosin-nigrosin mixture, whilst the eosinophil cells become red. The two granulations always show different shades in the triacid preparation as well; for the nigrosinophil cells stain a blacker hue.
This is a quite peculiar group, characteristic for the blood of the guinea-pig. It shews transitions in the blood, from large mononuclear to transitional and polynuclear forms, but is marked by the lack of any kind of granulation. Instead of the latter, we find in these cells a roundish, nucleus-like form in the protoplasm, which also takes the nuclear stains, and possibly is to be considered an accessory nucleus. We have received the impression that we have here to deal with a vacuole filled with substance secreted by the cell. In a large series of preparations, it is possible to obtain some elucidation of the development and fate of these appearances. They first appear as point-like granules in the protoplasm, bearing no relation to the cell nucleus; they gradually increase, and acquire a considerable circumference. When they have attained about the size of the cell nucleus, they, or rather their contents, appear to break through the protoplasmic membrane and to leave the cell.
The number of the vacuole containing cells is 15-20% of the colourless blood corpuscles.
Their appearance completely corresponds with that of human lymphocytes as described above. They make up 30-35% of the total number of leucocytes.
Now Kurloff in the course of extremely careful and laborious researches, estimated the total number of leucocytes, and then from the percentage numbers, the total quantity of pseudoeosinophil, neutrophil, eosinophil, vacuole containing cells, and lymphocytes, and could thus demonstrate that in uncomplicated cases of removal of the spleen, where inflammatory processes, accompanied by an increase of the polynuclear neutrophil corpuscles, were avoided, a gradual increase of the lymphocytes alone in course of time results. This may be a two- or threefold increase, whereas the numbers of all other elements remain unchanged.
Kurloff obtained his figures as follows: first he estimated the relative proportion of the different kinds of white blood corpuscles one to another in a large number of cells (500 to 1000). A count of this kind however gives no evidence as to whether one or other kind of cell is absolutely increased or diminished. A fall in the percentage of the lymph cells may be brought about by two quite different factors: (1) by a diminished production of lymphocytes, (2) by an increased influx of polynuclear forms, which naturally lowers the relative count of the lymphocytes. It was therefore necessary to obtain a method which would show alterations in the absolute number of the individual forms of leucocytes. Kurloff used for this purpose the "comparative field"; that is, he counted by the aid of a moveable stage the different forms which lay on a definite area (22 sq. mm.) of the dried blood preparation. This procedure gave very exact results, as only faultlessly prepared, and regularly spread preparations were used. The following figures (from Exp. II.) illustrate the method and its results:
| April 12 | 52% pseudo-eos. | 10% lymphocytes counted. |
| Sept. 2 (one month after the operation) | 22% " | 53% " " |
By the aid of the comparative surface, these figures were supplemented by the following averages. On each surface used for comparison were found:
| April 12 | 38 | white | = | 19.8 | pseudo-eos. | 10.6 | lymphocytes. |
| Sept. 2 | 81 | " | 18.0 | " | 46.9 | " |
From this example it follows without doubt, that the total number of the white blood corpuscles had about doubled itself, but that in this increase the lymphocytes exclusively were concerned, and the pseudo-eosinophil cells had not undergone the smallest increase.
The results which Kurloff obtained by means of this method in animals whose spleens had been removed, may be illustrated by one of his original researches and its accompanying chart and table.
Exp. I. Young female, weight 234 gr. Number of red corpuscles in a cubic millimeter of blood 5,780,000. Number of white 10,700. On April 19, 1888, the spleen was removed, the wound healed by first intention. The results of the further investigation of the blood are found in the following table.
From the chart and table, the number on the surface of comparison of the white blood corpuscles is seen to have more than doubled itself in the first seven months, and that this increase was solely dependent on the flooding of the blood by lymphocytes. The nucleated or bone-marrow elements and the large mononuclear cells remained continuously at the same level during the whole period. The changes in the percentage proportions ran somewhat differently. The percentages rose from 35 to 66% for the lymphocytes only, whilst for the other forms they distinctly fell: for the nucleated from 44% to 22% and for the large mononuclear from 18% to 9%. It was only in the course of the second year that a very considerable relative and absolute increase of the eosinophil cells appeared: the values rose gradually from about 1.0% to 28.9% or from 0.5 to 13.9 on each comparison area. The last examination of the blood in this animal was made on April 30, 1890, that is, two years after the removal of the spleen. The animal was quite healthy, bore four healthy young guinea-pigs by a father whose spleen had been removed. The young have a completely normal spleen, and their blood likewise shows no abnormalities.
Key to columns:
A -
B - Pseudo-eosinophil cells
C - Lymphocytes
D - Large mononuclear cells
E - Eosinophil cells
F - Nigrosinopil cells
G - On comparative surfaces
| Date | Leucocytes | Pseudo-eosinophil cells | Lymphocytes | Large mononuclear cells | Eosinophil cells | Nigrosinopil cells | ||||||||||||
| Total | On comparative surfaces | % | On comparative surfaces | % | On comparative surfaces | % | On comparative surfaces | % | On comparative surfaces | % | On comparative surfaces | |||||||
| 1888 | ||||||||||||||||||
| April 19 | 500 | — | 44.7 | — | 35.4 | — | 18.4 | — | 1.1 | — | 0.5 | — | ||||||
| 23 | 990 | 24 | 40.4 | 9.7 | 35.6 | 8.5 | 21.6 | 5.2 | 1.9 | 0.4 | 0.4 | 0.09 | ||||||
| May 1 | 858 | 28 | 47.0 | 13.6 | 32.6 | 9.1 | 18.0 | 5.0 | 0.9 | 0.2 | 0.3 | 0.08 | ||||||
| 8 | 934 | 28 | 45.2 | 12.6 | 40.3 | 11.3 | 14.3 | 4.0 | 0.6 | 0.2 | 0.4 | 0.1 | ||||||
| 16 | 1122 | 30 | 38.4 | 11.5 | 47.7 | 14.3 | 10.3 | 3.1 | 3.3 | 0.9 | 0.2 | 0.06 | ||||||
| 24 | 1722 | 35 | 40.1 | 14.0 | 35.0 | 12.2 | 23.6 | 8.3 | 1.0 | 0.3 | 0.1 | 0.03 | ||||||
| 30 | 900 | 30 | 36.6 | 10.9 | 44.4 | 13.3 | 18.4 | 5.5 | 0.1 | 0.03 | 0.3 | 0.09 | ||||||
| June 5 | 825 | 33 | 28.4 | 9.4 | 49.3 | 16.2 | 20.0 | 6.6 | 1.7 | 0.6 | 0.4 | 0.1 | ||||||
| 12 | 1314 | 33 | 28.0 | 9.3 | 49.0 | 16.2 | 20.0 | 6.6 | 2.2 | 0.7 | 0.8 | 0.3 | ||||||
| 19 | 917 | 37 | 32.4 | 11.9 | 52.3 | 19.3 | 14.5 | 5.4 | 0.6 | 0.3 | 0.2 | 0.07 | ||||||
| 28 | 802 | 42 | 30.5 | 12.8 | 56.4 | 23.7 | 11.7 | 4.9 | 0.7 | 0.3 | 0.4 | 0.2 | ||||||
| July 2 | 1062 | 56 | 16.5 | 9.2 | 57.1 | 31.9 | 25.6 | 10.3 | 1.2 | 0.7 | 1.2 | 0.7 | ||||||
| 9 | 1245 | 51 | 17.6 | 8.9 | 59.1 | 30.1 | 21.8 | 11.1 | 0.8 | 0.4 | 0.8 | 0.4 | ||||||
| 16 | 974 | 69 | 17.5 | 12.0 | 66.4 | 45.8 | 15.7 | 10.8 | 0.2 | 0.1 | 0.2 | 0.1 | ||||||
| 23 | 1156 | 58 | 21.7 | 12.6 | 67.2 | 38.9 | 9.5 | 5.5 | 1.5 | 0.9 | 0.2 | 0.1 | ||||||
| 30 | 802 | 54 | 20.2 | 10.7 | 65.4 | 34.6 | 12.8 | 6.8 | 1.4 | 0.7 | — | — | ||||||
| Aug. 6 | 910 | 52 | 21.7 | 11.3 | 67.3 | 34.9 | 9.7 | 4.9 | 1.0 | 0.5 | 0.3 | 0.2 | ||||||
| Sept. 6 | 815 | 51 | 23.0 | 11.7 | 65.3 | 33.5 | 9.8 | 4.9 | 0.9 | 0.5 | 0.4 | 0.2 | ||||||
| Oct. 5 | 625 | 62 | 26.4 | 16.3 | 64.4 | 39.9 | 8.5 | 5.2 | 0.6 | 0.4 | — | — | ||||||
| Nov. 4 | 800 | 58 | 22.5 | 13.0 | 66.4 | 38.5 | 9.6 | 7.3 | 0.9 | 0.5 | 0.5 | 0.2 | ||||||
| 1889 | ||||||||||||||||||
| April 10 | 700 | — | 29.8 | — | 53.3 | — | 14.8 | — | 1.2 | — | 0.6 | — | ||||||
| June 6 | 900 | 71 | 28.2 | 20.0 | 50.1 | 35.6 | 12.9 | 9.1 | 8.2 | 5.8 | 0.6 | 0.4 | ||||||
| Aug. 1 | 670 | 62 | 30.6 | 18.9 | 44.2 | 27.4 | 15.2 | 9.4 | 9.6 | 5.9 | 0.4 | 0.2 | ||||||
| Dec. 4 | 731 | 63 | 36.0 | 22.0 | 38.3 | 24.1 | 11.3 | 7.1 | 13.3 | 8.7 | 0.6 | 0.4 | ||||||
| 1890 | ||||||||||||||||||
| Feb. 2 | 622 | 51 | 32.3 | 16.5 | 30.1 | 15.3 | 11.1 | 5.6 | 26.0 | 13.2 | 0.5 | 0.2 | ||||||
| April 30 | 500 | 48 | 36.5 | 17.5 | 24.5 | 11.7 | 9.4 | 4.5 | 28.9 | 13.9 | 0.6 | 0.3 | ||||||
The results of further investigations, which we here shortly repeat in tabular form, shew that in this experiment No. I. we are not dealing with an abnormal phenomenon of an exceptional animal.
| No. of Expt. | Number of white blood corpuscles | ||
| Before the splenectomy | At the end of the first year | At the end of the second year | |
| 1 | 10,700 | 14,200 | 18,000 |
| 2 | 12,000 | 27,600 | 32,000 |
| 4 | 15,000 | 19,200 | 19,000 |
| Average | 12,600 | 20,333 | 23,300 |
By estimating the percentage proportion of the single kinds of white corpuscles, Kurloff obtained the following result:
| Before the operation | At the end of the first year | At the end of the second year | ||||||||||||
| Number of the Exper- iment | Polynuclear granular cells | Lympho- cytes | Mono- nuclear | Eosin- ophil | Polynuclear granular cells | Lympho- cytes | Mono- nuclear | Eosin- ophil | Polynuclear granular cells | Lympho- cytes | Mono- nuclear | Eosin- ophil | ||
| 1 | 4782 | 3788 | 1969 | 117 | 4232 | 1568 | 2101 | 170 | 6570 | 4410 | 1692 | 5202 | ||
| 2 | 6276 | 3360 | 2244 | 72 | 5464 | 16615 | 2980 | 2539 | 5824 | 20861 | 2688 | 2240 | ||
| 4 | 6715 | 5250 | 2595 | 450 | 6568 | 10041 | 3686 | 96 | 7108 | 3009 | 2138 | 7543 | ||
From these researches we draw the following conclusions.
1. The spleen is not an indispensable, vitally important organ for the guinea-pig, since that animal bears splenectomy without loss of health, developes normally, and gains well in weight.
2. The hypertrophy and hyperplasia of the lymph glands, particularly of the mesenteric glands, which develop after the operation correspond to a lymphocytosis, which makes its appearance in the course of the first year after the operation so constantly that it may be looked upon as a characteristic sign of the absence of the spleen. This increase may amount to double and more. We must therefore assume that the deficiency of splenic function may be met by the lymphatic glandular system. This period of lymphæmia may doubtless in some animals persist for years in exceptional cases; in the majority, however, the lymphæmia diminishes in the course of the first year, and indeed subnormal quantities of lymphocytes may then be produced.
3. The cells of the bone-marrow, on the contrary, and the polynuclear pseudoeosinophil cells do not show the least variation in the course of the first year. Bearing in mind that under normal conditions these cells are met with exclusively in the bone-marrow, and that inflammation in animals after removal of the spleen is accompanied by an acute pseudoeosinophil leucocytosis, exactly as in normal animals, one must admit that the production and function of this kind of cell are quite independent of the spleen. Hence there can be no doubt about their myelogenic nature.
4. It is especially important that the mononuclear and the leucocytes associated with them, undergo no increase. As these cells under normal circumstances occur both in the spleen and in the bone-marrow, we must assume that normally also the bone-marrow is responsible for the majority of this kind in the blood, and that the deficiency in the splenic contribution can be easily covered by a slightly raised activity of the bone-marrow. Were the share of the spleen important, from general biological considerations, an over-production of the kind of cell in question must occur in the vicarious organs.
5. The increase of the eosinophil cells, which constantly makes its appearance in the second year after the operation, is highly interesting, and leads to a really enormous rise in their absolute and relative numbers. Their percentage number once rose to 34.6%, and their absolute quantity amounted at the end of the second year on the average to 30-50-fold their original number (see table).
Hence it follows from Kurloff's researches that the spleen of the guinea-pig plays quite an unimportant part in the formation of the white blood corpuscles, and that after splenectomy in the first year compensation occurs only in the lymph-glands, followed in the second year by a great increase of the eosinophil cells. It is to be particularly insisted once again that the spleen has nothing at all to do with the formation of the pseudoeosinophil polynuclear cells, which are the analogues of the polynuclear neutrophils of man.
How do observations on man stand in the light of Kurloff's observations, which might be regarded as depending on peculiarities of the particular kind of animal?
Completely analogous material is afforded by cases, in which in healthy people a splenectomy has been necessary in consequence of trauma. Unfortunately the material available for this purpose is extremely rare; and it would be of the utmost value if the alterations of the blood in such a case were systematically studied for a period of years. We have ourselves begun our observations in two patients directly after the operation, but were unable to continue them, as death occurred within the first week after the extirpation. Up to the present only seven cases of rupture of the spleen with subsequent splenectomy have been published, as is stated in the collection of cases of v. Beck. In two only, of these seven cases, one of Riequer's (Breslau) the other of v. Beck's (Karlsruhe) was a cure effected. Through the courtesy of the above-mentioned gentlemen, we were able to investigate specimens from these two patients.