β. The clinical differences. Normoblasts are found almost invariably in all severe anæmias that are the result of trauma, inanition or organic disease of some kind. They are however mostly rather scanty, so that a preparation must be searched for some time before an example is found. But occasionally, most often in acute, but also in chronic anæmias, and even in cachectic conditions, every field shews one or more normoblasts.
V. Noorden was the first to describe a case in which in the course of a hæmorrhagic anæmia normoblasts temporarily appeared in such overwhelming numbers in the circulating blood, that the microscopic picture, which at the same time comprised a marked hyperleucocytosis, was almost similar to that of a myelogenous leukæmia. And as in addition to this occurrence the number of blood corpuscles was nearly doubled, v. Noorden gave it the distinctive name "blood crisis."
The following procedure is to be recommended for the investigation of the blood crisis:
1. Estimation of the absolute number of red blood corpuscles.
2. Estimation of the proportion of white to red corpuscles.
3. Estimation of the proportion of nucleated red to white corpuscles by means of the quadratic ocular diaphragm (see page 31) in the dry preparation.
For instance if we find in a case of anæmia, 3-1/2 millions of red blood corpuscles, the proportion of white to red corpuscles = 1/100 and that of the nucleated red to the white = 1/10, then in 1 cubic millimeter there are 3500 nucleated red corpuscles, that is for 1000 ordinary there is 1 nucleated corpuscle.
Megaloblasts on the contrary are never found in traumatic anæmias. And in chronic anæmias of the severest degree, the result for example of old syphilis, carcinoma of the stomach and so forth, one looks for them almost always in vain, although they are sometimes to be found in leukæmia. On the contrary, the conditions, apparently much milder, in which from the clinical history, ætiology and general objective symptoms pernicious anæmia is suggested, are almost without exception characterised by the appearance of megaloblasts in the blood. Nevertheless in very late stages of the disease they are always scanty, and a very tedious search through one or more specimens is often required to demonstrate their presence. Hence follows the rule, that the investigation of a case of severe anæmia should never be considered closed, before three or four preparations at least have been minutely searched for megaloblasts under an oil immersion objective.
This clinical difference between the two kinds of hæmatoblasts admits of but one natural conclusion, which primarily leaves untouched the question, so much discussed at the present time, whether the megalo- or normoblasts can change one to the other. In all cases of anæmia, in which the fresh formation occurs according to the normal type, only in greater quantity and more energetically, we find normoblasts. Almost all anæmias resulting from known causes: acute hæmorrhages, chronic hæmorrhages, poverty of blood from inanition, cachexias, blood poisons, hæmaglobinæmia and so forth,—in short all conditions rightly called, secondary, symptomatic anæmias,—may shew this increase of normal blood production. In the conditions, which Biermer, on the grounds of their clinical peculiarities, has distinguished as "essential, pernicious anæmia" megaloblasts on the contrary occur, and represent an embryonic type of development. The extent to which this type participates in the blood formation in pernicious anæmia is most simply demonstrated by the fact that megaloblasts are present in all cases of pernicious anæmia, as Laache first shewed, and in some cases form the preponderating portion of the blood discs. Whilst, therefore, in the ordinary kinds of anæmia we find that the red corpuscles tend to produce small forms, in pernicious anæmia, on the other hand, and exclusively in this form, we find a tendency in the opposite direction. This constant difference cannot be a chance result, but must depend on some constant law: in pernicious anæmia excessively large blood corpuscles are produced. Ehrlich's demonstration of megaloblasts has sufficed for this logical advance. All researches, which try to obscure or totally deny the distinction between megaloblasts and normoblasts are wrecked by the simple clinical fact that in pernicious anæmia the blood is megaloblastic.
The appearance of megaloblasts and megalocytes is therefore evidence that the regeneration of the blood in the bone-marrow is not proceeding in the normal manner, but in a way which approximates to the embryonic type. The extreme cases are naturally seldom, such as that of Rindfleisch, in which the whole bone-marrow was found full of megaloblasts. It is sufficiently conclusive for the pernicious nature of the case, "if only considerable portions but not the whole marrow, have lapsed into megaloblastic degeneration." We can now say that the megaloblastic metamorphosis is not a purposeful process, and for the following reasons: 1. Since the fresh formation of red blood corpuscles by means of the megaloblastic method is clearly much slower. This is especially borne out by the fact that the megaloblasts are present in the blood always in small numbers only, whilst the normoblasts, as above mentioned, are often found in much larger quantities. In agreement with this, "blood crises" are not to be observed in the megaloblastic anæmias. 2. Since the megalocytes which are formed from the megaloblasts possess in proportion to their volume a relatively smaller respiratory surface, and so constitute a type disadvantageous for anæmic conditions[10]. This is still more evident when we remember that the production of poikilocytes is on the contrary a serviceable process.