the cilia communicate to the fluids or other matters in contact with them, maintains a constant direction; unless in certain of the lower animals, in which the motion is often variable and arbitrary in direction, and might even be supposed to be voluntary. Thus in the windpipe of mammalia, the mucus is conveyed upwards towards the larynx, and, if a portion of the membrane be detached, matters will still be conveyed along the surface of the separated fragment in the same direction relatively to that surface, as before its separation.

The persistence of the ciliary motion for some time after death, and the regularity with which it goes on in parts separated from the rest of the body, sufficiently prove that, with the possible exceptions alluded to, it is not under the influence of the will of the animal, nor dependent for its production on the nervous centres, and it does not appear to be influenced in any way by stimulation or sudden destruction of these centres. The time during which it continues after death or separation differs in different kinds of animals, and is also materially influenced by temperature and by the nature of the fluid in contact with the surface. In warm-blooded animals the period varies from two or three hours to two days, or even more; being longer in summer than in the cold of winter. In frogs the motion may continue four or five days after destruction of the brain and spinal cord; and it has been seen in the gullet of the tortoise fifteen days after decapitation, continuing seven days after the muscles had ceased to be irritable.

Variations of temperature exert a very marked effect upon the rate and vigour of the motion of cilia. Thus, in warm-blooded animals it is altogether stopped if the temperature is lowered to 6° C., whereas, in cold-blooded animals, such as the frog and mussel, it goes on unimpaired at 0° C. The motion which has become quiescent from cold, may be revived by warmth, and becomes more active in proportion to the rise in temperature up to a certain point, which differs in warm and cold-blooded animals. In the former, this maximum temperature is about 45° C.; above this the movement quickly ceases, the cilia passing into a coagulated stiffened condition, known as heat-rigor, and which, if well marked, is not recovered from. The temperature of the body seems to be that which is most favourable to the action of the cilia; that is to say, they will, if removed from the body, work vigorously for a longer time at this temperature than at any other.

Cilia will continue to work for a time in the absence of free oxygen. This was shown by Sharpey, who noticed the movement of the cilia upon the gills of the tadpole to proceed for some hours, even when immersed in water which had been deprived of its oxygen by boiling. This experiment shows that like the substance of muscle, the protoplasm of the ciliated epithelium-cell can store up oxygen in a combined form for future use.

The immediate action of water is to increase the activity of cilia. Agents or conditions, on the other hand, which abstract water from the tissue, retard or arrest the action. Thus most of the common acid and saline solutions when concentrated arrest the action of cilia instantaneously in all animals, but dilution delays this effect, and when carried far enough, prevents it altogether. Fresh water soon arrests the motion in marine animals; but it evidently acts by destroying the epithelium-cells, which in these cases are adapted to a different medium. Even in air-breathing and fresh-water animals water has after a time the same action, provided the ciliated cells are detached, so that it can pass by imbibition into their protoplasm. Solutions of potash or soda, if extremely dilute, act like water, but more powerfully. Virchow observed that a diluted solution of either potash or soda would revive the movement of cilia after it had just ceased. The vapour of chloroform arrests ciliary action, but the motion revives again if the application of the vapour is discontinued (Lister).

Carbonic acid gas resembles chloroform in its action, rapidly arresting the movement if conveyed over a ciliated surface, but the action speedily recommences on again admitting air. The passage of the gas is, however, generally found to stimulate the movement at first.

Bile stops the action of cilia, while blood prolongs it in vertebrated animals; but the blood or serum of the vertebrata has quite an opposite effect on the cilia of invertebrate animals, arresting their motion almost instantaneously.

It was noticed by Steinbuch that a mechanical stimulus, insufficient to injure the cilia, such as that produced by the impulse of a current of fluid, acts markedly in exciting the activity of ciliary motion.

Electric stimulation, unless it causes injury to the ciliated surface, produces no obvious effect. Whatever views are entertained concerning the nature and source of the power by which the cilia act, it must be borne in mind that each ciliated cell is individually endowed with the faculty of producing motion, and that it possesses in itself whatever organic apparatus and whatever physical or vital property may be necessary for that end; for single epithelium cells are seen to exhibit the phenomenon long after they have been completely isolated.

Historical. Ciliary movement was first noticed (in the mussel) by de Heide in 1683, the movements of spermatozoa having been previously discovered by Ham and Leewenhock. Subsequently the movements were noticed in various situations. A comprehensive account of the structure, distribution, and mode of action of cilia was given by Sharpey in the article "Cilia," in Todd and Bowman's Cyclopædia. That article, which appeared in 1835, was the result of much laborious investigation, and still forms the basis of our knowledge on the subject.

Simultaneously with Sharpey's article a full description was also given by Purkinje and Valentin, including an account of the discovery of this phenomenon in mammals, birds, and reptiles, and of the literature up to that time (De phænomeno generali et fundamentali motûs vibratorii continui, 1835). The account by Engelmann in his article on Protoplasm and Ciliary movement' in Hermann's Handbuch der Physiologie also includes an historical sketch of the subject up to 1879.

RECENT LITERATURE.

Aeby, Chr., Die Herkunft des Pigmentes im Epithel, Medic. Centralbl., No. 16, 1885. Ballowitz, E., Untersuchungen ü. die Struktur der Spermatozoen, &c., Zeitschr. f. wiss. Zool., Bd. 50, 1890; and Archiv f. mikr. Anat., Bd. xxxvi., 1890.

Barbacci, O., Sulla rigenerazione fisiologica degli elementi epiteliali di rivestimento, Archivio per le scienze med., Vol. xiii., 1888.

Beltzow, A., Zur Regeneration des Epithels der Harnblase, Virchow's Archiv, Bd. 97, 1885. Bizzozero, G., Ueber den Bau des geschichteten Pflasterepithels, Internat. Monatsschr. f. Anat. u. Histol. ii., 1885; Ueber die schlauchförmigen Drüsen des Magendarmcanals und die Beziehungen ihres Epithels zu dem Oberflächenepithel der Schleimhaut, Arch. f. mikrosk. Anat., Bd. xxxiii.,

1889.

1884.

Bockendahl, A., Ueber die Regeneration des Trachealepithels, Arch. f. mikr. Anat., Bd. xxiv., Cajal, Ramón y, Contribution à l'étude des cellules anastomosées des épitheliums pavimenteux stratifiés, Internat. Monatsschr. f. Anat. u. Histol., iii., 1886.

Eberth, C., Ueber Einschlüsse in Epithelzellen, Fortschritte d. Medizin, viii., 1890. Flemming, W., Zur Kenntniss der Regeneration der Epidermis beim Säugethier, Arch. f. mikr. Anat., xxiii., 1884; Ueber die Regeneration durch mitotische Zelltheilung, Arch. f. mikr. Anat., xxiv., 1884.

Frenzel, J., Zum feineren Bau des Wimperapparates, Archiv f. mikr. Anat., Bd. xxviii., 1886. Gad, J., Ueber Blut-capillarhaltiges Epithel, Verhandl. d. Berliner physiol. Gesellschaft, Arch. f. Anat. u. Phys., Physiol. Abth., 1890.

Griffini, L., Contribuzione alla patologia del tessuto epiteliale cilindrico, Archivio per le scienze mediche, viii., and Arch. ital. de Biologie, v., 1884.

Haycraft, J. B., and Carlier, E. W., Note on the transformation of ciliated and stratified squamous epithelium as a result of the application of friction, Proceedings of the R. Society of Edinburgh, 1888.

Hotzen, E., Verhornung innerer Epithelien, Inaug. Diss., Kiel, 1890.

Ide, Manille, La membrane des cellules du corps muqueux de Malpighi, La Cellule, t. iv., 1888; Nouvelles observations s. l. cellules epith., Ibid., t. v. 1889.

Just, A., Zur Histologie und Physiologie des Flimmerepithels, Breslauer ärztl. Zeitschr., 1885. Kölliker, Ueber die Entstehung des Pigments in den Oberhautgebilden, Sitzungsber. der Würzburger Phys.-Med. Gesellsch., 1887.

Kraft, H., Zur Physiologie des Flimmerepithels bei Wirbelthieren, Pflüger's Archiv, xlvii., 1890. List, J. H., Studien an Epithelien: 1. Ueber Wanderzellen in Epithel, Archiv f. mikrosk. Anat., Bd. xxv., 1885; Ueber Becherzellen, Archiv f. mikr. Anat., Bd. xxvii., 1886.

Oehl, E., Microscopisch-anatomische Untersuchungen zum Studium der Epidermis und Cutis der Palma manus, Dermatol. Studien, 1889.

Paneth, J., Ueber die secernirenden Zellen des Dünndarm-Epithels, Arch. f. mikrosk. Anatomie, Bd. xxxi., 1888.

Peters, A., Ueber die Regeneration des Endothels der Cornea, Arch. f. mikr. Anat., xxxiii., 1889. Ranvier, L., De l'éléidine et de la repartition de cette substance dans la peau, la muqueuse buccale et la muqueuse œsophagienne des vertébrés, Arch. de physiologie, 1884; Des vacuoles des cellules caliciformes, des mouvements de ces vacuoles et des phénomènes intimes de la sécrétion du mucus, Compt. rend., T. 104, 1887.

Schäfer, E. A., On the structure of amaboid protoplasm, &c., with a suggestion as to the mechanism of ciliary action, Proc. of the Royal Society, 1891.

Severin, Untersuchungen über das Mundepithel bei Säugethieren, mit Bezug auf Verhornung, Regeneration und Art der Nervenendigung, Archiv f. mikr. Anat., xxvi., 1885.

Slavunos, G. L., Unters. ü. das Elcidin u. den Verhornungsprocess, u. s. w., Würzburg Verhandl., xxiv., 1890.

Strahl, H., Beiträge zur Kenntniss des Baues des Esophagus und der Haut, Arch. für Anat. und Physiol., Anatomische Abtheilung, 1889.

Tornier, O., Ueber Bürstenbesätze an Drüsenepithelien, Archiv f. mikr. Anat., Bd. xxvii., 1886. For other papers on epithelium, see Literature of Skin and of various organs.

1 A translation of this article is to be found in the Quarterly Journal of Microscopical Science, for 1880.

THE CONNECTIVE TISSUES.

Three principal modifications or varieties of connective tissue have long been recognized and separately described, viz., areolar tissue, fibrous tissue and elastic tissue. Others, however, belong unmistakeably to the same group, as the study of their structure and the history of their development in the mesoblast clearly show. Of these the most important are adipose tissue, retiform and lymphoid tissue, cartilage, bone and the elements of the blood and lymph. It will be convenient to study the last-named elements before the structure of the connective tissues proper is considered.

THE BLOOD.

The most striking external character of the blood is its well-known colour, which is bright red approaching to scarlet in the arteries, but of a dark purple or modena tint in the veins. It is a somewhat clammy and consistent liquid, a little heavier than water, its specific gravity being about 1055; it has a saltish taste, a slight alkaline reaction, and a peculiar faint odour.

To the naked eye the blood appears opaque and homogeneous; but, when examined with the microscope, either while within the minute vessels, or when spread out into a thin layer upon a piece of glass, it is seen to consist of a transparent colourless fluid, named the "lymph of the blood," "liquor sanguinis," or "plasma," and minute solid particles or corpuscles immersed in it. These corpuscles are of two kinds, the coloured and the colourless: the former are by far the more abundant, and have been long known as "the red particles," or "globules," of the blood; the "colourless," "white," or "pale corpuscles," on the other hand, being fewer in number and less conspicuous, were later in being generally recognised.

When blood is drawn from the vessels, the liquor sanguinis separates into two parts;-into fibrin, which becomes solid and takes the form of fine interlacing filaments, and a pale yellowish liquid named serum.

In a cubic millimeter of healthy human blood there are on an average 5,000,000 red corpuscles (Vierordt) and 10,000 white corpuscles. The number of white corpuscles varies much more than that of the red, and the proportion of the white to the red is variously given at from 1:1000 to 1:250. There are said to be fewer red corpuscles in the female (4,500,000 in a cubic millimeter according to Welcker).

The numeration of the blood-corpuscles is readily performed. A little blood, obtained by pricking the finger, is measured in a capillary tube, and is then mixed with a measured amount (say 100 times its volume) of dilute solution of sulphate of soda, or some other salt which will maintain its fluidity and at the same time preserve the corpuscles nearly unaltered; the latter can then be counted in a small known quantity of the mixture. This part of the operation is effected by placing a drop of the mixture in the middle of a glass "cell" of a certain depth (say th of a millimeter), the bottom of which is ruled in squares, the sides of which are of a known dimension (say again mill.). If now a covering glass is placed over the cell so as to touch the drop, the latter will form a layer of the mixture mill. deep, and the part above each square will represent a cube of liquid the sides of which measure mill. So that by counting the number of corpuscles in ten squares, after allowing them time to subside, and multiplying the result by 10,000, the number in a cubic millimeter of the blood is obtained. The methods of Hayem and Nachet, Gowers, and Thoma are based on the above principle. The average results obtained by recent investigators agree closely with the original estimates of Vierordt and Welcker, 1

1 G. Oliver (Croonian Lectures, Lancet, 1896, vol. 1) has introduced a new method of accurately estimating the number of red blood corpuscles without the labour of enumeration. Many valuable observations on the conditions affecting their number will also be found here.

RED CORPUSCLES OF THE BLOOD.

These are not spherical, as the name "globules," by which they were formerly designated, would seem to imply, but flattened or disk-shaped. Those of the human blood (fig. 239 and fig. 240, A) have a nearly circular outline, like a piece of coin, and most of them also present a shallow cup-like depression or dimple on both surfaces; their usual figure is, therefore, that of biconcave disks. Their magnitude differs somewhat even in the same drop of blood, and it has been variously assigned by authors; but the prevalent size may be stated at 3200th of an inch (007 to 008 millimeter) in diameter, and about one-fourth of that in thickness. A few corpuscles may usually be found which are not more than about one half this size (microcytes), and others which are rather larger (up to about soooth of an inch), and

Fig. 239.-HUMAN BLOOD AS SEEN ON THE WARM STAGE. MAGNIFIED ABOUT 1000 DIAMETERS. (E. A. S.)

r, r, single red corpuscles seen lying flat; r', r', red corpuscles on their edge and viewed in profile; r", red corpuscles arranged in rouleaux; c, c, crenate red corpuscles; p, a finely granular pale corpuscle; 9, a coarsely granular pale corpuscle. Both have two or three distinct vacuoles, and were undergoing changes of shape at the moment of, observation; in g, a nucleus also is visible.

every gradation in size between these two extremes may be met with, but the great majority average 30th of an inch under normal conditions. In some diseases, especially pernicious anæmia, the relative number of microcytes is greatly increased.

In mammiferous animals generally, the red corpuscles are shaped as in man, except in the camel tribe, in which they have an elliptical outline. In birds, reptiles, amphibia, and most fishes, they are oval disks with a central elevation on both surfaces (fig. 240, B, and fig. 245, from the frog), the height and extent of which, as well as the proportionate length and breadth of the oval, vary in different instances, so that in some fishes the elliptical form is almost shortened into a circle.

400

The size of the corpuscles differs greatly in the different classes of Vertebrata; they are largest in the Amphibia. Thus in the frog they are about th of an inch long and 17th broad; in Proteus anguineus, th of an inch long and th broad; in Amphiuma tridactylum, where they are largest, the red corpuscles are one-third larger than those of the Proteus. In birds they range in length from about 26th to th of an inch. Amongst mammals the elephant has the largest red blood-corpuscles (20th of an inch); those of the dog average 3500th of an inch; those of the sheepth of an inch; the goat was long supposed to have the smallest (th of an inch), but Gulliver found them about half this size in the Meminna and Napu deer.

3224

In observations upon the blood of different races of mankind, Richardson found no constant difference, the average diameter of the red blood-corpuscle being th of an inch. The corpuscles of many mammals, and notably the dog among the common domestic animals, approach so nearly in size to the human blood-corpuscles as to be indistinguishable from them.

When viewed singly by transmitted light the coloured corpuscles do not appear red, but merely of a reddish-yellow tinge, or yellowish-green in venous blood. It is

1 The one-thousandth part of a millimeter is often known as a micro-millimeter or micron, and is represented by the Greek letter μ. The diameter of a red blood corpuscle is then expressed as 7-8 microns (7μ-8)

only when the light traverses a number of corpuscles that a distinct red colour is produced.

In consequence of the biconcave shape of the corpuscle, it looks darker in the middle than at the edge when viewed with only a moderate magnifying power, or at

Fig. 240.-HUMAN RED CORPUS-
CLES (A) AND BLOOD CORPUSCLES
OF THE FROG (B) PLACED SIDE
BY SIDE TO SHOW RELATIVE
SIZE. 500 DIAMETERS.

1, shows their broad surface; 2, one seen edgeways; 3, shows the effect of dilute acetic acid; the nucleus has become distinct (from Wagner).

A

B

a distant focus; but the middle of the corpuscle appears lighter than the periphery when a close focus or a very high magnifying power is employed.

The red disks, when blood is drawn from the vessels, sink in the plasma; they have a singular tendency to run together, and to cohere by their broad surfaces, so as to form by their aggregation cylindrical columns, like piles or rouleaus of money, and the rolls or piles themselves join together into an irregular network (figs. 239 and 241). Generally the corpuscles separate on a slight impulse, and they may then unite again. The phenomenon will take place in blood which has been in any way brought to a standstill within the living vessels as well as in blood that has stood for some hours after it has been drawn, and also when the globules are immersed in serum in place of liquor sanguinis.

COLLECTED

(after Henle).

INTO

ROLLS

It has been shown by Norris that disks which float completely immersed in any fluid will, when the fluid comes to rest, tend to adhere together in the form of rouleaus provided that the surface of the disks is of a nature not to be wetted by the fluid in which they float. Thus cork disks which have been weighted so that they neither rise nor sink in water do not adhere together so long as they are freely wetted by the water, but if their surfaces are coated with a thin film of fatty substance the disks tend to run together into rouleaus. As it is probable (see below, Structure of Red Corpuscles) that the red disks do actually possess a superficial film of fatty substance, the facts pointed out by Norris appear to suggest a reasonable explanation of the rouleau-formation which occurs in blood which has been allowed to come to rest.

The human blood-corpuscles, as well as those of the lower animals, often present deviations from the natural shape, which are most probably due to causes acting after the blood has been drawn from the vessels, but in some instances depend upon abnormal conditions previously existing in the blood. Thus, it is not unusual for many of them to appear shrunken and crenated, when exposed under the microscope (fig. 239, c, c; fig. 242, f), and the number of corpuscles so altered often appears to increase during the time of observation. This is, perhaps, the most common change; it occurs whenever the density of the plasma is increased by the addition of a neutral salt, and is one of the first effects of the passage of an electric shock. The corpuscles may become distorted in various other ways, and corrugated on the surface; not unfrequently one of their concave sides is bent out, and they acquire a cup-like figure.

Gulliver made the curious discovery that the corpuscles of the Mexican deer and some allied species present very singular forms, doubtless in consequence of exposure; the figures they assume are various, but most of them become lengthened and pointed at the ends, and then often slightly bent, not unlike caraway-seeds.