SPECIAL HISTOLOGY.

I. BLOOD AND BLOOD-FORMING ORGANS, HEART, BLOOD-VESSELS, AND LYMPH-VESSELS.

A. BLOOD AND LYMPH.

1. FORMATION OF BLOOD.

EARLY in the development of the embryo there appear in a portion of the extra-embryonic area of the blastoderm, known as the area vasculosa, definite masses of cells, derived from the mesenchyme, and spoken of as blood islands, which are intimately connected with the formation of the blood. If these blood islands be examined at a certain stage, free cells are seen lying in their center, apparently derived from the central cells of the islands; the cells surrounding them represent the elements which later go to form the primitive vascular walls. The free elements are the first blood-cells of the embryo. The blood-cells thus developed enter the circulation by means of blood channels formed by the confluence of the blood islands. These grow toward the embryo and later join the large central vessels. The origin of these blood islands is still an open question. Some authors contend that they arise from the mesoblast (P. Mayer, 87, 93; K. Ziegler; van der Stricht, 92), others that they are of entodermic origin (Kupffer, 78; Gensch; Rückert, 88; C. K. Hoffmann, 93, I; 93, II; Mehnert, 96). At a certain period the embryonic blood consists principally of nucleated red cells, which proliferate in the circulation by indirect division. The colorless blood-cells, the development of which is not yet fully understood, appear later. It is possible that they also are elements of the blood islands, which do not contain any hemoglobin. In a later period of embryonic life the liver becomes a blood-forming organ. Recent investigations have, however, shown that it does not take a direct part in the formation of the blood, but only serves as an area in which the blood-corpuscles proliferate during their slow passage through its vessels. The blind sac-like endings of the venous capillaries seem to be particularly adapted for this purpose, as in them the blood current stagnates, and it is here that the greater number of blood-cells reveal mitotic figures. The

newly formed elements are finally swept away by the blood stream and enter the general circulation (van der Stricht, 92; v. Kostanecki, 92, III). Many investigators believe that the red blood-cells have an entirely different origin in the liver-namely, from the large polynuclear, giant cells, which are thought to arise either from the cells of the capillaries or from the liver-cells (Kuborn, M. Schmidt). Late in fetal life and in the adult, the red bone-marrow and the spleen are the organs which form the red blood-cells. The lymphatic glands and the spleen produce the white blood-cells. In addition to the nucleated red corpuscles which are present up to a certain stage of development, nonnucleated red blood-cells also appear. The number of the latter increases, until finally they are found almost exclusively in the blood of the new-born infant.

The blood of the adult consists of a clear, fluid, coagulable substance, the blood plasma, and of formed elements suspended in this intercellular substance. The formed elements are: (a) Red bloodcorpuscles (erythrocytes); (b) white blood-corpuscles (leucocytes); and (c) the blood platelets of Bizzozero (82), Hayem. Besides these, there are present particles of fat, and, as H. F. Müller (96) has recently shown, also hemokonia.

2. RED BLOOD-CORPUSCLES.

In man and nearly all mammalia the great majority of the red blood-corpuscles are nonnucleated, biconcave circular discs with rounded edges. They have smooth surfaces, are transparent, pale yellow in color, and very elastic. No method has as yet been devised to demonstrate a nucleus in these cells, and there is no doubt that the red blood-discs of the human adult and of mammalia are devoid, in the histologic sense, of a nucleus capable of differentiation (compare Lavdowsky; Arnold, 96). They are therefore peculiarly modified cells.

If fresh blood be left for some time undisturbed, the blood-discs adhere to each other by their flattened surfaces, grouping themselves in rouleaux.

By certain reagents the clear and transparent contents of the blood-corpuscles can be separated into two substances—a staining and a nonstaining. The first consists of the blood pigment, or hemoglobin, which can be dissolved; the second of a colorless substance, the stroma, which presents itself in various forms (protoplasm of the cell).

Hemoglobin is a very complex proteid which may be decomposed into a globulin and a pigment hematin. The hemoglobin of the majority of animals crystallizes in the form of rhombic prisms ; in the squirrel, however, in hexagonal plates, and in the guinea-pig in tetrahedra. Hematin combines with hydrochloric acid to form hemin, or Teichmann's crystals, of brownish color, rhombic shape, and microscopic size. They are of much value in lego-medical

work, since they may be obtained from blood, no matter how old, and are characteristic of hemoglobin. They may be obtained from very small quantities of blood pigment.

The stroma probably contains the hemoglobin in solution. The question as to whether the erythrocytes possess a membrane or not is difficult to answer, although in all probability they do (Lavdowsky).

If a small drop of blood pressed from a small puncture is placed on a slide and covered with a cover-glass, the red bloodcells soon become changed. This is due to the evaporation of water in the blood plasma, causing an increased concentration of the sodium chloride contained, which in turn draws water from the blood-cells The shrinkage which follows produces a characteristic

change in the form of the cells, which assume a crenated or stellate shape. The red blood-cells of blood mounted in normal salt become crenated in a short time for the same reason. Red bloodcells are variously affected by different fluids. In water they become spheric and lose their hemoglobin by solution. Their remains then appear as clear, spheric, indistinct blood shadows, which may, however, be again rendered distinct by staining with iodin. Dilute acetic acid has a similar but more rapid action, with this peculiarity, that before becoming paler the blood-cells momentarily assume a darker hue. Bile, even when taken from the animal furnishing the blood, exerts a peculiar influence upon the red blood-cells; they first become distended, and then suddenly appear to explode into

small fragments. Dilute solutions of tannic acid cause the hemoglobin to leave the blood-cells, and coagulate in the form of a small globule at the edge of the blood-cell. In alkalies of moderate strength the red blood-cells break down in a few moments.

Besides the disc-shaped red blood-cells, every well-made preparation shows a few small, spheric, nonnucleated cells containing hemoglobin. These, however, have received as yet but little attention.

M. Bethe makes the statement that human blood and the blood of mammalia contain corpuscles of different sizes, bearing a definite numerical relationship to each other. "If they be classified according to their size, and the percentage of each class be calculated, the result will show a nearly constant proportional graphic curve varying but slightly, according

b

Fig. 150.-Red blood-corpuscles from various vertebrate animals; 1000 (Welker's model): a, From proteus (Olm); b, from frog; c, from lizard; d, from sparrow; e, from camel; ƒ and g, from man; h, from myoxus glis; i, from goat; k, from musk-deer.

to the animal species." According to M. Bethe, dry preparations of human and animal blood may be distinguished from each other, with the exception of the blood of the guinea-pig which presents a curve identical with that of human blood.

The red blood-cells of mammalia, excepting those of the llama and camel species, are in shape and structure similar to those of

man.

The red blood-cells of the llama and camel have the shape of an ellipsoid, flattened at its short axis, but also nonnucleated.

We have already made mention of the fact that the embryonal erythrocytes are nucleated; the question now arises as to how, in the course of their development, they lose their nuclei. Three possibilities confront us: First, either the embryonal blood-cells are destroyed and gradually replaced by previously existing nonnucle

ated elements; or, second, the nonnucleated red cells are formed from the nucleated by an absorption of the nucleus (or what appears to be such to the eye of the observer, Arnold, 96); or, finally, the nucleus is extruded from the original nucleated cell. According to recent investigations (Howell) the third possibility represents the change as it actually takes place.

In all vertebrate animals except mammalia, the red bloodcorpuscles are nucleated. They are elliptic discs with a biconvex center corresponding to the position of the nucleus. The bloodcells of the amphibia (frog) are well adapted for study on account of their size. They are long and, as a rule, contain an elongated nucleus with a coarse, dense chromatin framework, which gives them an almost homogeneous appearance. The cell-body may be divided, as in mammalia, into stroma and hemoglobin. When subjected to certain reagents, the contour of the cells appears double and sharply defined. This condition is, however, no proof of the existence of a membrane; yet, as modern observers have demonstrated, a membrane may be totally or partly isolated (Lavdowsky). The blood-cells of birds, reptiles and fishes are similarly constructed.

The diameter of the erythrocytes varies greatly in different vertebrate animals, but is constant in each species. We append a table of their number in a cubic millimeter and size in man and certain animals as compiled by Rollett (71, II) and M. Bethe: