Histology of the Blood, Normal and Pathological

by Paul Ehrlich; Adolf Lazarus

E. Neumann regards Rindfleisch's doctrine as untenable, since the process which he observed is chiefly the result of a severe injury of the blood from the sodium chloride solution and the teasing. If a method of preparation be chosen which protects the blood as far as possible, and avoids every chemical and physical alteration, the exit of the nucleus as described by Rindfleisch does not occur.

The view of Kölliker and Neumann that the nuclei gradually decay in the interior of the cell is not supported by the observation of a process, but by the fact that in suitable material, for instance, fœtal bone-marrow, liver blood, and leukæmic blood, the transition from erythroblast to erythrocyte is shewn by all phases of nuclear metamorphosis. v. Recklinghausen professes to have directly observed the dissolution of the nucleus within the cell in rabbit's blood, kept living in a moist chamber. Pappenheim's opinion however, that in this case processes are concerned such as Maragliano and Castellino have described as artificial necrobiosis, seems in this connection worthy of consideration.

Just as with regard to the formation of erythrocytes the views differ one from another, so also with regard to the "free" nuclei which come under observation in numerous preparations. Kölliker has taught that these nuclei are not quite free, but are always surrounded by a minute border of protoplasm. On the other hand Rindfleisch regards these nuclei as having migrated from, or having been cast off by the erythroblasts; and Neumann explains them as the early forms of erythroblasts. Ehrlich was the first to endeavour to effect a compromise between the directly opposed views of Rindfleisch and Neumann. He taught that both kinds take part in the production of the red discs. From blood preparations which contain numerous normoblasts, for instance in "blood crises" (see p. 62), an unbroken series of pictures can easily be put together shewing how the nucleus of the erythroblast leaves the cell, and at last produces the appearance of the so-called free nucleus. It must be expressly mentioned that these pictures are only to be found in specimens in whose preparation pressure of any kind upon the blood has been avoided. Further, however rich a blood may be in normoblasts, the metamorphosis of the nucleus as described by Neumann, is practically never to be observed. It is quite otherwise with the megaloblasts. Amongst them, few examples are to be found in which traces at least of the destruction and solution of the nucleus are not shewn, and in a blood preparation of pernicious anæmia, which is not too poor in megaloblasts, one can construct step by step the unbroken series from megaloblasts with a complete nucleus through all stages of Karyorrhexis and Karyolysis to the megalocytes, as the process is described by Neumann[9].

From Ehrlich's observations it follows, that the normoblasts become normocytes by extrusion or emigration of the nucleus, the megaloblasts become megalocytes by degeneration of the nucleus within the cell.

M. B. Schmidt without making use of the principal distinction made by Ehrlich, also concludes from his researches on sections of the bone-marrow of animals in extra-uterine life, that both kinds of erythrocyte formation occur.

Quite recently Pappenheim, partly in conjunction with O. Israel, has carried out very thorough researches on these particular points. As the subject for observation he chose the blood of embryonic mice. He was able in the first place, like Rindfleisch, to produce the exit of the nuclei from the cells by the addition of "physiological" salt solution to fresh blood, and is of the opinion that the exit of the nucleus from the erythroblasts only takes place artificially.

In embryonic blood the metamorphosis to erythrocytes occurs exclusively by nuclear destruction and solution within the cell, be it in the case of megalo- or gigantoblasts or of cells of the size of the normal red blood corpuscle.

The free nuclei that are observed, whose appearance Pappenheim explains by a preceding solution of the protoplasm (plasmolysis), he regards, in opposition to Rindfleisch and Neumann, not as the beginnings of a developmental series, but as the surviving remnants of the degenerated dying blood cells. Clinical observation, certainly, does not support this conception of Pappenheim's; in as much as in suitable cases with numerous free nuclei (leukæmia, blood crises) transitional forms, which according to Pappenheim must necessarily be present, are not to be found. Moreover, in alluding to a case of leukæmia of this kind, this author himself admits that the appearance of free nuclei can be explained in this instance by the exit of the nucleus.

Although Pappenheim, as above mentioned, recognises no difference between megaloblasts and normoblasts in embryonic blood as far as the fate of the nucleus is concerned, he nevertheless decidedly supports Ehrlich's separation of the erythroblasts into these two groups, as two hæmatogenetically distinct species of cells. He does not regard as distinguishing characteristics, the size and hæmoglobin content of the cells—although as we have described above, these are in general different in normo- and megaloblasts—for these two properties undergo such great variations as to increase considerably under certain circumstances the difficulty of diagnosis of individual cells. The chief characteristic is, as Ehrlich has always particularly insisted, the constitution of the nucleus. The nuclei of cells which are with certainty to be reckoned among the normoblasts are marked by the absence of structure, their sharply defined contour, their intense affinity for nuclear stains. That is by properties which histology sums up under the name Pyknosis (Pfitzner) and recognises as signs of old age. The nuclei of the megaloblasts are round, shew a good deal of structure, and stain far less deeply.