Histology of the Blood, Normal and Pathological

by Paul Ehrlich; Adolf Lazarus

The argument based on figures such as these assumes that the function of the bone-marrow is continuous; an assumption which Uskoff indeed seems to make.

But if the bone-marrow is constantly absorbing the lymphocytes to such an extent, it is quite incomprehensible how the normal condition of the blood can be preserved, bearing in mind the extent of the bone-marrow and the rate of the circulation. All evidence indeed tends to shew that on the contrary the bone-marrow performs its functions discontinuously, inasmuch as elements continually grow to maturity in the bone-marrow, as we have above explained, but they only emigrate at certain times as the result of chemical stimuli. It is obvious à priori from this consideration how inconclusive must be the results of experiments such as these of Roietzky[17].

Far more important for the elucidation of the function of the bone-marrow are clinical observations on cases in which considerable portions of the bone-marrow are replaced by tissue of another kind. We may best divide the observations on this point into two groups: 1. malignant tumours of the bone-marrow, 2. the so-called acute leukæmia.

There are unfortunately very few available observations as yet upon the first group. Still rarer are the cases in which as is necessary the whole bone-marrow has been subjected to an exhaustive examination, which alone affords adequate evidence of the extent of the defect.

Amongst the changes of the bone-marrow arising from tumours one may distinguish two groups, according to the nature of the condition of the blood. The first type is exemplified by a case of Nothnagel published in his work on lymphadenia ossium. Here during life the blood shewed, in the main, the features of a simple severe anæmia; but in addition isolated normoblasts, small marrow cells, and moderate leucocytosis. The autopsy, at which the whole skeletal system was subjected systematically to an exact examination, shewed a complete atrophy of the bone-marrow, and replacement of the same by the tumour masses. In this case then the condition of the blood in vivo is satisfactorily explained by the absence of function of bone-marrow. Nothnagel conjectured that the formation of the scanty nucleated red blood corpuscles occurred vicariously in the spleen, that of the leucocytes in the lymph glands.

In the second series to which the cases of Israel and Leyden, as well as the recently published one of J. Epstein from Neusser's wards, belong, the blood shews, besides the usual anæmic changes, other anomalies which are peculiar partly to pernicious anæmia, partly to myelogenic leukæmia. In Epstein's case of metastatic carcinoma of the bone-marrow, there was found a considerable anæmia, with numerous nucleated red blood corpuscles both of the normo- and megaloblastic type; their nuclei presented the strangest shapes, due not merely to typical nuclear division, but also to nuclear degeneration. The white blood corpuscles were much increased, their proportion to the red was 1/25 to 1/40; the increase concerned in the main the large mononuclear forms, which bore for the most part neutrophil granulation, and were therefore to be called myelocytes. In all the specimens, only two eosinophil cells were found[18].

The explanation of a blood picture of this kind, apart from the purely anæmic changes, is by no means easy, as Epstein rightly observes. The appearance of myelocytes is most readily explained by a direct stimulation of the remaining bone-marrow by the surrounding masses of tumour. In this, the mechanical factor is less concerned than the chemical metabolic products of the tumour masses; which at first act on the adjacent tissue in specially strong concentration, and also in a negatively chemiotactic manner on the wandering cells. This view receives support from the careful work of Reinbach on the behaviour of the leucocytes in malignant tumours. Out of 40 cases examined, in only one, of lymphosarcoma complicated with tuberculosis, were myelocytes found in the blood, amounting to about 0.5-1.0% of the white blood corpuscles. The autopsy shewed isolated yellowish white foci of growth in the bone-marrow, reaching the size of a sixpenny piece. Bearing in mind that in none of the other 39 cases were myelocytes demonstrated, one does not hesitate to explain their presence in the blood in this single case by the metastases in the bone-marrow. The small extent of the latter is likewise the cause of the small percentage of the myelocytes.

In explaining the presence of the megaloblasts in the blood of Epstein's patient we must keep before us what we have said elsewhere on this kind of cell. They are not present in the normal bone-marrow; they arise on the contrary, according to our view, when a specific morbid agent acts upon the bone-marrow, as we must assume is the case in the pernicious forms of anæmia. In the cases of anæmia from tumours, in which we find megaloblasts in large numbers in the blood, we must likewise assume that chemical stimuli proceed from the tumours, leading to the formation of megaloblasts in the bone-marrow.

The presence of megaloblasts in the bone-marrow does not itself cause their appearance in the blood, for in pernicious anæmia the bone-marrow may be filled with megaloblasts, and yet only very scanty examples are to be found in the blood. Whether the emigration of the megaloblasts from the bone-marrow into the blood-stream is in general to be referred to chemical stimuli, as it is in the particular case of Epstein's, or to mechanical causes, cannot at present be decided.