appear to be undergoing division (fig. 257). They are amoeboid cells, the protoplasm of which is coloured by hæmoglobin, and they closely resemble, in fact, the nucleated red blood-corpuscles of the embryo. It appears therefore probable that the cells in question are descendants of the embryonic red blood-corpuscles, and that they are transformed into the ordinary blood-discs by the gradual atrophy and disappearance of the nucleus and the moulding of the coloured cell-substance into the shape of the biconcave red corpuscles. Appearances such as are exhibited by some of the corpuscles which are delineated in fig. 257, certainly indicate atrophy of the nucleus. The amoeboid movements of which these corpuscles are capable may assist them to pass into the blood-capillaries, the walls of which are, in mammals, less distinct and continuous than in other parts, with the single exception of the spleen. But it would appear from the observations of Bizzozero and Torre that in birds the capillary walls are complete, and that all the erythroblasts are intravascular, i.e., are found within the venous capillaries and not in the tissue of the marrow. These venous capillaries are relatively large, and the blood-stream in them must be exceedingly slow. The fully developed red corpuscles lie in the axis of the vessel, the erythroblasts and leucocytes towards the periphery. These statements have been confirmed in the main by Denys, who has also subjected the marrow in birds to a careful examination. Denys states, however, that the coloured erythroblasts are derived from colourless erythroblasts lying next to the capillary wall, and that while this transformation into red corpuscles is going on within the vessels, the marrow cells outside the vessels are multiplying and forming white blood corpuscles. 3. Origin from white corpuscles.-The view which long obtained most prevalence, is that the red discs are developed from the white corpuscles. There are, however, no recorded observations of recent date which show conclusively that the red corpuscles are thus developed in the circulating blood, although some observers are of opinion that such transformation may occur in the marrow. 4. In the spleen. It has long been believed that the formation of red blood-corpuscles is carried on in the spleen-pulp, but this view has been in many quarters supplanted by the contrary one that a destruction of red corpuscles rather than a new formation may there take place, in support of which many facts were brought forward by Kölliker. The former view has, however, been again brought into prominence by Bizzozero, who describes in the spleenpulp after severe loss of blood, nucleated red corpuscles like those in the marrow, and further finds that there are more red as well as white corpuscles in the blood of the splenic vein than in that of the corresponding artery. These statements only apply, however, to certain animals. 5. From the elementary particles or blood-platelets.-Hayem described these as the precursors of the red blood-corpuscles in mammals. To them he applied the name "hæmatoblasts," and he maintains that they acquire colour, and by a gradual increase in size become directly transformed into red corpuscles. In support of this view he points out that red corpuscles which are much smaller than the ordinary ones are to be almost always met with in blood, and that these smaller forms are especially numerous in cases where there has been previously a considerable loss of blood, and in which, therefore, it may well be supposed that a new formation of red corpuscles is proceeding; and further, that they present every transition between the blood-tablets and the red discs.2 In the frog Hayem describes as hæmatoblasts, spindle-shaped cells something like the white corpuscles, but of more delicate appearance (like the corpuscle marked p in fig. 245). These become, according to him, converted directly into red corpuscles, after undergoing an increase of size and a change of shape, in addition to the accession of colouring matter. They had been long previously noticed by Recklinghausen, and regarded as transition forms between the white and red corpuscles. Morphology of the red corpuscles. It is obvious from the study of the structure of the mammalian red blood-disks that they are not morphologically to be regarded as cells. For they lack a most important morphological constituent of the cell, viz., the nucleus, nor do they exhibit any other sign of cell-structure. 1 According to Howell the partially atrophied nucleus becomes extruded, and then dissolved. A similar account of the development of the red discs was given by Zimmermann; but many of the transitional forms which he described were red corpuscles which had become decolorised. The same may probably be said regarding the "invisible corpuscles" of Norris ("Physiology and Pathology of the Blood," 1882). Chemically also, as has been shown by Halliburton and Friend, the red corpuscles lack substances, such as cell-albumin and nucleo-albumin, which are characteristic of typical animal cells. They contain, however, a small amount of cell-globulin,' and this appears to be their only proteid. Further, although originally formed from and within protoplasm (see above, Intracellular development, and Development in marrow), they have lost all amoeboid properties-in fact, as the study of their formation within the angioblasts shows, the protoplasm from which they are formed becomes transformed into little but a solution of hæmoglobin, which as their development proceeds, becomes confined by a delicate pellicle of "stroma substance." This may itself be a deposit formed around the hæmoglobin-globules by the cell-protoplasm, or may be a modified remainder of that protoplasm which is left around the globule. On the other hand, the nucleated red corpuscle of oviparous vertebrates, although its general structure and mode of development show it to be morphologically a cell, yet has in the adult none of the functional characteristics of cells. Nor so far as we know is it in the adult condition capable of undergoing division and multiplication, although the nucleus retains the structure and chemical composition which is typical of cell-nuclei. The cell-body, on the other hand, has both histologically and chemically lost the properties of cell-protoplasm, and as in the case of the mammalian corpuscle is wholly transformed into a homogeneous mass or solution of hæmoglobin with a delicate enclosing pellicle. Some authors have, it is true, described a reticular structure within these corpuscles, but there is little doubt that such reticulum has been artificially produced by the reagents used to fix the corpuscles. These nucleated corpuscles of ovipara differ from the nucleated corpuscles of the mammalian embryo, for the latter are true functional cells, capable of division, and exhibiting amoeboid phenomena, and in short differing from a typical animal cell, such as the white corpuscle, only in the presence of hæmoglobin in their protoplasm. The nucleated coloured cells of the marrow are in all respects similar to them. Historical. The development of blood-corpuscles in isolated patches in the vascular area of the chick was first recognised by Pander, who termed the patches "blood-islands." Remak, and after him, His and Kölliker, described the first vessels in the vascular area of the chick as originating in the form of a solid cord of mesoblastic cells, arranged so as to form a network; the peripheral cells of the vascular cords becoming flattened and forming the epithelium of the vessels, whilst the centrally placed cells become directly converted into blood-corpuscles, acquiring colour first of all at certain points-the blood-islands of Pander-and fluid accumulating between them to form the liquor sanguinis. His stated, moreover, that the blood-vessels within the body of the embryo originate as ingrowths from these vessels of the vascular area.2 Stricker was the first to describe the formation of blood-vessels by the hollowing out of connective tissue-cells, and Afanasieff and Klein proved that the blood-islands of Pander were cells of the mesoblast, in the interior of which blood-corpuscles had made their appearance, and that the containing cells became the first blood-vessels. Klein's account was confirmed, and in some particulars modified, by Balfour. The account above given of the formation of vessels and blood-corpuscles in the vascular area of mammals is derived from observations upon the embryo of the guinea-pig. The production of red blood-disks in the interior of certain cells of the connective tissue was first noticed by me in the subcutaneous connective tissue of the new-born rat, and subsequently in the embryos of a number of different animals, and these observations were confirmed by Ranvier-who terms the connective tissue-cells concerned in the process" vasoformative cells "-as well as by Leboucq and others. The discovery of the important fact that in the adult condition the main if not the only seat of formation of red blood-corpuscles is the red marrow of the bones, is due to the researches of Neumann, which were first published in 1868. RECENT LITERATURE. Auerbach, L., Die Blutkörperchen der Batrachien, Anat. Anzeiger, 1890. Bizzozero, G., Ueber die Entstehung der rothen Blutkörperchen während des Extrauterinlebens, Moleschott's Untersuch. zur Naturlehre, xiii, 1883; Ueber die Bildung der rothen Blutkörperchen Virchow's Archiv, Bd. 95, 1884, Arch. f. mikr. Anat., Bd. xxxv., 1890; Nouvelles recherches s. la structure de la moelle des os chez les oiseaux, Archives ital. de biologie, T. xiv., 1891. 1 This has since been shown by Halliburton to be a nucleo-proteid. 2 Vide Embryology, p. 25. Bizzozero and Torre, Archivio per le scienze de Torino, IV., 1882; Moleschott's Untersuchungen, Bd. xii., and Virchow's Archiv, Bd. 95. Copeman, The detection of human blood, Lancet, 1889. Corning, H. K., Zur Frage der Blutbildung aus dem Entoderm, Arch. f. mikr. Anat., Bd. 36, 1890. Crookshank, Edgar M., Flagellated protozoa in the blood of diseased and apparently healthy animals, Journal of the Royal Microsc. Society, vol. vi, 1886. Danilewsky, B., Die Hämatozoen der Kaltblüter, Archiv für mikrosk. Anat., Bl. xxiv, 1885. Denys, La structure de la moelle des os et la genèse du sang chez les oiseaux, La Cellule, t. iv., 1888. Dogiel, J., Neue Untersuchungen über die Ursache der Geldrollenbildung im Blute des Menschen und der Thiere, Arch. f. Anat. u. Phys., Physiol. Abth., 1883; Zur Physiologie der Lymphkörperchen, Archiv f. Anat. u. Physiol., Phys. Abth., 1884. Éberth, C. J., Zur Kenntniss der Blutplättchen bei den niederen Wirbelthieren, Festschrift für A. v. Kölliker, 1887. Eberth, C. J., und Aly, W., Ueber die Vermehrung der rothen Blutkörper, Fortschr. d. Medicin, III, 1885. Ehrlich, P., Zur Physiologie und Pathologie der Blutscheiben, Charité-Annalen, X, 1885. Feuerstack, W., Die Entwicklung der rothen Blutkörperchen, Zeitschr. f. wissenschaftl. Zoologie, Bd. 38, 1883. Fleming, W., Studien ü. Regeneration der Gewebe, Arch. f. mikr. Anatomie, xxiv., 1885. Foà, P., Beitrag zum Studium der Structur der rothen Blutkörperchen der Säugethiere, Beiträge zur pathologischen Anatomie von E. Ziegler, Bd. v, 1889. Gibson, J. Lockhart, The blood-forming organs and blood formation, Journ. of Anat. and Physiol., vol. xx, 1885. Gostling, T., On the increase in number of white corpuscles in the blood in inflammation, Medico-chir. Transact., LI, 1887. Gram, Ch., Untersuchungen über die Grösse der rothen Blutkörperchen im Normalzustande und bei verschiedenen Krankheiten, Fortschritte d. Medicin, No. 2, 1884. Gulland, G. L., The nature and varieties of leucocytes, Laboratory Reports of the Royal College of Physicians of Edinburgh, 1891. Halliburton, W. D., On the haemoglobin crystals of rodents' blood, Quart. Journ. of Micr. Science, Aug. 1887. Halliburton, W. D., and Friend, W. M., The stroma of the red corpuscles, Journal of Physiology, vol. x, 1889. Hamburger, H. J., Ueber die durch Salz- und Rohrzuckerlösungen bewirkten Veränderungen der Blutkörperchen, Archiv f. Anat. u. Phys., Phys. Abth., 1887; Die Permeabilität der rothen Blutkörperchen, &c., Zeitsch. f. Biol., 1890. Haycraft, J. B., and Carlier, E. W., Morphological changes that occur in the human blood during coagulation, Proceedings of the R. Society of Edinburgh, 1888. Hayem, G., Des globules rouges à noyau dans le sang de l'adulte: Contribution à l'étude des altérations morphologiques des globules rouges, Archives de Physiologie, 1883; Du sang et de sc altérations anatomiques, Paris, 1899. Hogyes, Fr., A new process of demonstrating the structure of the red blood corpuscles (Hungarian), Abstract in Centralbl. f. Physiologie, 1889. Howell, W. H., The life history of the formed elements of the blood, especially the red bloodcorpuscles, Journal of Morphology, IV., 1890. Hunter, W., The duration of life of red blood-corpuscles after transfusion, British Medical Journal, 1887. Kowalewsky, N., Uber die Wirkung der Salze auf die rothen Blutkörperchen, Medic. Centralb., 1887 and 1890. Läker, C., Studien über die Blutscheibchen und den angeblichen Zerfall der weissen Blutkörperchen bei der Blutgerinnung, Sitzungsber. d. Wiener Academie d. Wiss., III. Abth., 1883; Beobachtungen an den geformten Bestandtheilen des Blutes, Sitzungsb. d. Wiener Akad., Bd. 93, 1886. Lawdowsky, M., Mikroskopische Untersuchungen einiger Lebensvorgänge des Blutes, Virchow's Archiv, Bd. 96, 97, 1884. Lewis, T. K., Further observations on flagellated organisms in the blood of animals, Quart. Journ. of Microsc. Science, July, 1884. Limbeck, R. von, Klinische Beobacht. ü. die Resistenz der roten Blutkörperchen, &c., Prager medic. Wochensch., 1890. Löwit, M., Ueber die Bildung rother und weisser Blutkörperchen, Prager med. Wochenschr., viii, 1883; Ueber die Bildung rother und weisser Blutkörperchen, Sitzungsber. d. Wiener Akad., Abth. III., 1888; Beiträge zu der Lehre von der Blutgerinnung: I., Ueber das coagulative Vermögen der Blutplättchen, Sitzungsber. d. Wiener Akad., III. Abth., Bd. 89; II., Ueber die Bedeutung der Blutplättchen, Ibid., Bd. 90, 1884; Ueber Neubildung und Zerfall weisser Blutkörperchen, Sitzungsber. der Wiener Akademie, Bd. 92, Juni, 1885; Ueber die Beziehung der Blutplättchen zur Blutgerinnung und Thrombose, Prager med. Wochenschr., No. 6, 7, 1886; Die Beobachtung der Circulation beim Warmblüter: Ein Beitrag zur Entstehung des weissen Thrombus, Archiv f. experim. Pathol., Bd. xxxiii, 1887; Die Umwandlung der Erythroblasten in rothen Blutkörperchen, Sitzungsber. d. Wiener Akad., 1887; Ueber die Präexistenz der Blutplättchen und die Zahl der weissen Blutkörperchen im normalen Blute des Menschen, Virchow's Arch., Bd. 117, 1889. Mackenzie, S., The Lettsomian lectures on Anæmia, Brit. Med. Journal, Jan., 1891. Malassez, Sur l'origine et la formation des globules rouges dans la moelle des os, Arch. de physiol., t. ix., 1882. Meissels, W., Ueber die Structur der rothen Blutkörperchen, Wiener Presse, Jahrg. xxx, 1889. Meltzer, S. J., und Welch, W. H., Zur Histiophysik der rothen Blutkörperchen, Centralb. f. d. med. Wiss., No. 41, 1884. Metschnikoff, E., Ueber die Beziehung der Phagocyten zu den Milzbrandbacillen, Virchow's Archiv, Bd. 97, 1884. Minot, C. S., Zur Morphologie der Blutkörperchen, Anat. Anzeiger, 1890. Moss, A., Die Umwandlung der rothen Blutkörperchen in Leukocyten und die Necrobiose der rothen Blutkörperchen bei der Coagulation und Eiterung, Virchow's Archiv, Bd. 109, 1887. Müller, F., Zur Frage der Blutbildung, Wiener Sitzungsber., Math.-naturw. Cl., Bd. 98, 1889. Neumann, E., Ueber die Entwickl. roter Blutkörperchen im neugebildeten Knochenmark, Virchow's Arch., 1890. Norris, The physiology and pathology of the blood, 1882. Osler, W., On certain problems in the physiology of the blood-corpuscles, British Medical Journal, and New York Medical Record, 1886. Otto, J. G., Untersuchungen über die Blutkörperchenzahl und den Hämoglobingehalt des Blutes, Pflüger's Archiv, Bd. 36, 1885. Pekelhäring, C. A., Ueber die Diapedese der farblosen Blutkörperchen bei der Entzündung, Virchow's Archiv, Bd. 104, 1886. Pohl, J., Die Vermehrung der farblosen Zellen im Blute nach Nahrungsaufnahme, Archiv für experim. Path. u. Pharmakol., 1888; Ueber die Einfluss von Arzneistoffen auf die Zahl der kreisenden weissen Blutkörperchen, Ibid. Reinecke, W., Ueber Blutkörperzählungen, Inaug. Diss., Halle, 1889. Reinke, F., Exper. Untersuchungen ue. d. Proliferation, &c., der Leucocyten, Beitr. zur pathol. Anatomie, v., 1890. Sanfelice, Fr., Genèse des corpuscles rouges dans la moelle des os, Arch. ital. de biol. xiii., 1890. Schimmelbusch, C., Die Blutplättchen und die Blutgerinnung, Virchow's Arch., Bd. 101. 1885. Schmidt, A., Recherches sur les leucocytes du sang, Archives de Physiologie, 1883. Siegel, F., u. Maydl, C., Ueber Zählungen der Blutkörperchen, Wiener med. Jahrbücher, 1881. Spronck, C. H. H., Over regeneratie en hyperplasie van leucocyten in het circulcerend bloed, Nederl. Zijdschr. vocr Geneeskunde, 1889. Stricker, S., Photogramm eines farblosen Blutkörperchens, Arbeiten a. d. path. Instit., Wien, 1890. Török, L., Die Theilung der rothen Blutzellen bei Amphibien. Math. u. naturwissensch. Berichte aus Ungarn, 1890. CONNECTIVE TISSUE PROPER. Areolar tissue.-If we make a cut through the skin and proceed to raise it from the subjacent parts, we observe that it is loosely connected to them by a soft filamentous substance of considerable tenacity and elasticity, and having, when free from fat, a white fleecy aspect; this is the substance known as areolar tissue. In like manner the areolar tissue is found underneath the serous and mucous membranes which are spread over various internal surfaces, and serves to attach these membranes to the parts which they line or invest; and as under the skin it is named "subcutaneous," so in the last-mentioned situations it is called "subserous" and "submucous" areolar tissue. But on proceeding further we find this substance lying between the muscles, the blood-vessels, and other deep-seated parts, occupying, in short, the intervals between the different organs of the body where they are not otherwise insulated, and thence named "intermediate;" very generally, also, it becomes more consistent and membranous immediately around these organs, and under the name of the "investing" areolar tissue, affords each of them a special sheath. It thus forms inclosing sheaths for the muscles, the nerves, the bloodvessels, and other parts. Whilst the areolar tissue might thus be said in some scuse both to connect and to insulate entire organs, it also performs the same office in regard to the finer parts of which these organs are made up; for this end it enters between the fibres of the muscles, uniting them into bundles; it connects the several membranous layers of the hollow viscera, and binds together the lobes and lobules of compound glands; it also accompanies the vessels and nerves within these organs, following their branches nearly to their finest divisions, and affording them support and protection. This portion of the areolar tissue has been named the "penctrating," "constituent," or "parenchymal.” It thus appears that the areolar is one of the most general and most extensively distributed of the tissues. It is, moreover, continuous throughout the body, and from one region it may be traced without interruption into any other, however distant; a fact not without interest in practical medicine, seeing that in this way dropsical waters, air, blood, and urine, effused into the areolar tissues, and even the matter of suppuration, when not confined in an abscess, may spread far from the spot where they were first introduced or deposited. On stretching out a portion of areolar tissue by drawing gently asunder the parts between which it lies, it presents an appearance to the naked eye of a multitude of fine, soft, and somewhat elastic threads, quite transparent and colourless, like spun glass; these are intermixed with fine transparent films, or delicate membranous laminæ, and both threads and laminæ cross one another irregularly and in all imaginable directions, leaving open interstices or areolae between them. These meshes are, of course, more apparent when the tissue is thus stretched out; it is plain also that they are not closed cells, as the term "cellular tissue" which was formerly used to denote the areolar tissue, might seem to imply, but merely interspaces, which open freely into one another: many of them are occupied by the fat, which, however, does not lie loose in the areolar spaces, but is enclosed in its own vesicles. A small quantity of colourless transparent fluid of the nature of lymph is also present in the areolar tissue, but, in health, not more than is sufficient to moisten it. On comparing the areolar tissue of different parts, it is observed in some to be more loose and open in texture, in others more dense and close, according as free movement or firm connection between parts is to be provided for. Fibrous tissue. When the fine bundles of connective tissue are disposed for the most part in one or two directions, instead of interlacing in every direction as |