Book - A text-book of histology arranged upon an embryological basis (1913) 1-2

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Lewis FT. and Stöhr P. A Text-book of Histology Arranged upon an Embryological Basis. (1913) P. Blakiston’s Son and Co., 539 pp., 495 figs.

   Histology with Embryological Basis (1913):   Part I. 1.1. Cytology | 1.2. General Histology | 1.3. Special Histology
Part II. 2.1. The Preparation of Microscopical Specimens | 2.2. The Examination of Microscopical Specimens
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Part I. Microscopic Anatomy

II. General Histology


Segmentation and the Formation of the Germ Layers

The body is composed of groups of similarly differentiated cells, similar therefore in form and function. Such groups are known as tissues. Histology (Greek, IO-TO'S, "a textile fabric") is the science of tissues, and histogenesis deals with their origin. There are as many tissues in the body as there are "sorts of substance;" thus the liver consists essentially of hepatic tissue, and the bones of osseous tissue. All of these, however, are modifications of a small number of fundamental tissues, the development of which may now be considered.

It has already been stated that a new individual begins existence as a single cell, the fertilized ovum. This cell then divides by mitosis into a pair of cells, Fig. 25, A; and these again divide, making a group of four, Fig. 25, B. By repeated mitosis a mass of cells is produced, which because of its resemblance to a mulberry, is called a morula (Fig. 25, C). Development to this point is known as the segmentation of the ovum.

A section through the morula of the rabbit is shown in Fig. 25, D. An outer layer of cells surrounds the inner cell mass. Soon a cup-shaped cleft, crescentic in vertical section, forms between the outer and inner cells as shown in E, and this cleft enlarges until the entire structure becomes a thin-walled vesicle, within and attached to one pole of which is the inner cell mass (Fig. 25, F). Cells from this mass gradually spread beneath the outer layer until they form a complete lining for the vesicle. The inner layer is called entoderm, and the outer layer ectoderm.

Before the entoderm has encircled the vesicle, a third layer has appeared between the other two. This middle layer is the mesoderm (Fig. 25, G). It arises from the place where the ectoderm and entoderm blend with one another. The layers may be separated and floated apart except at this spot where they are "tied together." This place is therefore called the primitive knot. The mesoderm also spreads laterally from a longitudinal thickening of the ectoderm, which extends backward from the primitive knot and marks out the future longitudinal axis of the embryo. This thickening is the primitive streak. Arising from the primitive knot and primitive streak, the mesoderm spreads out rapidly between the ectoderm and entoderm, and very soon it splits into two layers (Fig. 25, H). One of them (the somatic layer) is closely applied to the ectoderm, and the other (the splanchnic layer) to the entoderm. Between them is a cavity, known as the body cavity or coelom, which in the adult becomes subdivided into the peritoneal, pleural, and pericardial cavities. The ectoderm and the somatic mesoderm together form the body wall or somatopleure; the entoderm and the splanchnic mesoderm together form the intestinal wall or splanchnopleure.

Reviewing the preceding paragraphs it is seen that the fertilized ovum, through segmentation, forms a morula, which later becomes a vesicle composed of three germ layers, the outer or ectoderm, inner or entoderm, and middle or mesoderm. By the folding of these layers the body as a whole acquires its form; and by their growth and differentiation all the organs and tissues are produced, together with the fetal membranes which surround the embryo. Omitting for the present all reference to the membranes, the fundamental changes which the germ layers undergo may be briefly considered, as follows:

Ectoderm. A portion of the ectoderm forms a layer of cells covering the body of the embryo. In the adult this becomes the outer layer of the skin, or the epidermis, and from it, hairs, nails and the mammary, sebaceous and sweat glands develop. It is reflected under the eyelids and over the front of the eye, and forms the lachrymal glands. It etxends into the external auditory opening and there forms the ceruminous glands; and into the nasal, oral, anal and urogenital apertures. Within the mouth it forms the salivary glands, the enamel of the teeth, and the cells associated with the sense of taste. Thus it extends far back toward the pharynx, and dorsally, in its deepest part, it produces the anterior lobe of the hypophysis, which will be described in a later chapter. In the nose it also extends far inward, so that it lines the accessory cavities which push out from the nasal cavity into certain bones of the head, and it forms the olfactory cells. An inpocketing of the ectoderm produces the lining of the deep portion of the ear, including the auditory cells, and, as will be seen, the ectoderm gives rise to the lens and retina of the eye. Thus the ectoderm not only forms the outer covering of the body, with extensions into the several apertures, but it produces various sensory cells which are stimulated from external sources.

The second great derivative of the ectoderm is the nervous system. It arises in young embryos as the medullary groove. This is a longitudinal groove or furrow, situated in front of the primitive knot and appearing in cross section as a median dorsal depression (Fig. 25, G and H). Later the groove becomes a tube by the coalescence of its dorsal edges, which are about to unite in Fig. 25, H. The tube then becomes completely separated from the epidermal layer of ectoderm, as in Fig. 29.

The closure of the medullary groove to form a tube begins near the anterior end of the embryo and proceeds backward. Thus for a time the tube opens to the exterior both anteriorly, at the anterior neuropore, and posteriorly, at the posterior neuropore. Eventually the neuropores become closed over, and the tube is then whoUy detached from the epidermal layer. The form of the tube is shown in Fig. 27, which represents a dissected reconstruction of a chick embryo. In this dissection the epidermal layer, which covers the upper or dorsal surface of the embryo, has been almost all removed. A portion of it which forms a fold under the head and around the anterior neuropore has been left in place, and also a portion around the rhomboidal sinus, which may be regarded as an expanded posterior neuropore. By removing the epidermal layer, the medullary tube has been exposed. Anteriorly it shows a succession of expansions which are to form the brain, and also a pair of lateral outpocketings, or optic vesicles, each of which will become the retina of an eye. Posteriorly the tube is slender, and this part becomes the spinal cord. The brain and spinal cord, which are derived directly from the medullary tube, constitute the central nervous system. The peripheral nervous system consists of bundles of nerve fibers which ramify throughout the body, together with masses of nerve cells associated with these fibers. The nerve cells are detached ectodermal cells, arising chiefly from the dorsal part of the medullary groove, and the fibers are protoplasmic outgrowths of these detached cells and of others which remain in the wall of the medullary tube. Thus the entire nervous system, central and peripheral, is ectodermal in origin.


A-C represent surface views of the two-cell stage, four-cell stage and morula respectively. D-H are vertical sections. In D and the inner cell mass is heavily shaded. Ect., ectoderm. Ent., entoderm Mes., mesoderm.

Entoderm. Before considering the chief derivatives of the entoderm, the notochord (or chorda dorsalis) may be briefly described. In the lowest vertebrates it is an important supporting structure, and is regarded as "the primitive forerunner of the vertebral column." It arises in young mammalian embryos as a median longitudinal band of cells in the entodermal layer, immediately below the floor of the medullary groove. In the diagram, Fig. 25, H, it is shown as an elevation; in Fig. 29, it appears as a group of cells completely detached from the underlying entoderm. It then forms a longitudinal rod extending forward from the primitive knot to the under side of the brain, as seen in the longitudinal section of the chick embryo, Fig. 28. Later it becomes surrounded by mesodermal cells, which develop into the bodies (or centra) of the vertebrae together with the intervertebral ligaments between them. These are shown in Fig. 26, A, as alternating light and dark areas respectively. The notochord in passing through them shows "segmental flexures" (Minot). In the vertebral column of a fish (Fig. 26, B) the central notochordal rod has expanded between the bodies of the vertebrae so as to form large lenticular masses of gelatinous pulp. These retain a very slender connection with one another. In the human adult, the notochord is represented by the series of detached expansions, or nuclei pulposi, one of which occurs in each intervertebral ligament (Fig. 26, C). These nuclei are composed of a peculiar tissue, the development of which has been described by L. W. Williams (Amer. Journ. Anat., 1908, vol. 8, pp. 251284). The notochord is very rarely the source of tumors. Occasionally, owing to its connection with the entoderm, which is retained longest anteriorly, it gives rise to a pharyngeal recess (Huber, Anat. Record, 1912, vol. 6, pp. 373-404).

FIG. 26. THE NOTOCHORD. A, in a sheep embryo of 14.6 mm. (after Minot); B, in a cod fish; C, in man (after Dwight).

In young mammalian embryos the entire entoderm, with the notochordal cells included in its dorsal part, forms the lining of a spherical sac, known as the yolk-sac (Fig. 25, H). In birds the mass of yolk, which may be regarded as lodged in the thickened ventral wall of the yolk-sac, is so extensive that the cavity of the sac is merely a flattened dorsal cleft. The yolk-sac gives rise to the entire intestinal tube, together with all its outgrowths. They are therefore lined with entoderm, and they develop as follows.

At first, in the chick embryo (Figs. 27 and 28) a flattened finger-like extension of the yolk-sac projects forward into the head, under the notochord. This outpocketing is the fore-gut, which gives rise to the pharynx, oesophagus, stomach, and anterior part of the small intestine. Near its anterior extremity it comes in contact with the entoderm and fuses with it, thus forming the oral membrane. By the rupture of this membrane, an opening from the exterior into the pharynx is produced.

Similarly the hind-gut develops as a pocket from the posterior part of the yolk-sac. It gives rise to the lower portion of the small intestine and the entire large intestine, and fuses with the ectoderm, forming the cloacal membrane. In later stages the ventral part of the posterior end of the hind-gut becomes cut off from the dorsal part; the ventral subdivision forms the bladder, and the dorsal subdivision becomes the lowest part of the rectum. At the same time the cloacal membrane is correspondingly subdivided into the urogenital membrane which closes the outlet of the bladder, and the anal membrane which closes the rectum. Later these membranes rupture, and the line of separation between ectoderm and entoderm is then difficult to determine. The entoderm apparently lines the entire urethra in the female, but only the upper or prostatic portion in the male; the remainder is lined with ectoderm.

In addition to forming the lining of the pharynx and entire digestive tube, together with the bladder and its outlet, the entoderm lines the following important organs, which arise as outgrowths of the pharynx and digestive tube: the auditory tube, extending from the pharynx to the ear; the thyreoid gland and certain constituents of the thymus; the entire respiratory tract, including the larynx, trachea and lungs; the liver; and the pancreas.

Mesoderm. The mesoderm has already been described as forming splanchnic and somatic layers. These are indicated in the diagram Fig. 25, H, but are more accurately shown in Fig. 29, which corresponds to the upper part of Fig. 25, H, under higher magnification. Where the somatic and splanchnic layers come together they are greatly thickened, and the thickened part becomes cut into block-like masses by a series of transverse clefts. The masses are called mesodermic somites, and a pair of them occurs in each transverse segment of the body. They increase in number as new ones become cut off from the unsegmented mesoderm in the posterior part of the embryo. At first each somite may contain a cavity, which is an extension of the ccelom, but the cavity is soon obliterated by a plug of cells. In dorsal view some of the somites are shown on the right side of Fig. 27; the rest have been cut away.


FlG. 27 represents a dorsal view. The ectoderm has been removed except around the rhomboidal sinus and under the head. On the left side, all the mesoderm except the blood vessels has also been removed; a. portion including nine somites remains on the right side. The lowest layer beneath the vessels, is the entoderm. Fig. 28 is a median sagittal section, except that the entire heart has been included. Ant. neur., anterior neuropore; Med. groove, medullary groove; Med. tube, medullary tube; Mes. som., mesodermic somite; Opt. ves., optic vesicle; Oral mem., oral membrane; Peric. cav., pericardial cavity; Pr. knot, primitive knot; Pr. str., primitive streak; R. sinus, rhomboidal sinus; Vit. v., vitelline vein; W. duct, Wolffian duct.

In later stages each somite gives rise to a stream of cells which spread around the medullary tube, nojochord and aorta After these cells have been given off, the somite appears as a plate-like structure (Fig. 30), known as the dermo-myotome. The principal derivative of the dermomyotome is the voluntary musculature of the body. In producing the various voluntary or skeletal muscles, certain cells of the dermo-myotome become transformed into muscle fibers. These are at first arranged in segmental masses, but the masses become subdivided into groups representing the individual muscles. The groups become separated from one another and shift to their final positions. Subsequently they acquire their connections with the bones, which develop later than the muscles. The remainder of the dermo-myotome breaks up into cells which are contributed to the deep portion of the skin.

FIG. 29. TRANSVERSE SECTION OF A RABBIT EMBRYO MEASURING 4.4 MM. (pj DAYS). X6o. FIG. 30. TRANSVERSE SECTION OF A RABBIT EMBRYO MEASURING 5 MM. (n DAYS). X4O. Ect., ectoderm; Ent., entpderm; Int., intestine; Med. tube, medullary tube; Msnch., mesenchyma; Msth., mesodennal epithelium; Nch., notochord; Som., somatopleurej Som. mes., somatic mesoderm; Spl., splanchnopleure; Spl. mes., splanchnic mesoderm; W. d., Wolffian duct.

Connecting the somites with the lateral somatic and splanchnic layers of the mesoderm, there is a narrow neck of cells (as seen in cross section, Fig. 29) which is known as the intermediate cell mass, or nephrotome. The nephrotomes at first are not segmentally divided, but form the floor of a longitudinal groove in the mesoderm, lateral to the somites (Fig. 27). The nephrotomes give rise dorsally to a longitudinal cord of cells, which later becomes a tube, and is known as the Wolffian duct (Figs. 27, 29, and 30). It lies in the groove above the nephrotomes. This duct grows posteriorly and acquires an opening into the entodermal bladder. The nephrotomes then become separated from the somites and from the lateral layers of the mesoderm, and their cells become arranged so as to form coiled tubes, which empty into the Wolffian duct. In this way the mesoderm gives rise to the Tenal system, which consists essentially of coiled mesodennal tubes, receiving urinary products from the blood and conveying them through the Wolffian duct to the bladder. Later, parts of the urinary system lose their primary function and become the ducts of the genital system.

The lateral somatic and splanchnic layers of the mesoderm produce the lining of the pleural, pericardial, and peritoneal subdivisions of the ccelom, as already stated: They give rise also to an important tissue known as mesenchyma. With the production of mesenchyma the tissues of the embryo may be divided into two sorts, namely, epithelium which covers an external or an internal surface of the body, and mesenchyma which fills the space between two layers of epithelium. These relations are clearly shown in the cross section of the abdomen (Fig. 30). The body wall consists of a layer of ectodermal epithelium externally, and of mesodermal epithelium internally, with a thick layer of mesenchyma between the two. Similarly the intestinal wall consists of mesodermal epithelium toward the ccelom, and entodermal epithelium toward the intestine, with mesenchyma between them. Epithelium is thus produced by all the germ layers, but mesenchyma is almost exclusively the product of the mesoderm. It is formed not only from the lateral splanchnic and somatic layers of the mesoderm, but also from the somites. The tissue which has been described as spreading from the somites around the medullary tube, notochord and blood vessels, and into the deep portion of the skin, is mesenchyma. It also surrounds the tubules derived from the nephrotome.


Epi. and M. T., Ectodermal epithelium of the epidermis and medullary tube, respectively. N., nucleus, P., protoplasm, and I. S., intercellular substance of a mesenchymal cell. Two of these cells show mitotic figures. B. V., Blood vessel, lined with endothelium. One of the blood vessels contains an embryonic red blood corpuscle.

Under higher magnification, as in Fig. 31, it is seen that epithelium is a layer of closely compacted cells, but that mesenchyma is a protoplasmic network, the meshes of which are filled with a fluid intercellular substance. If this substance is abundant, the nuclei of the mesenchyma are widely separated, as in the figure; but if it is scanty they are quite close together. Mesenchyma gives rise to a great variety of tissues, including involuntary muscle, adipose tissue, cartilage, and bone. Both the cells and the intercellular substance may become variously modified. The most widespread derivative of mesenchyma is connective tissue, which invests the nerves, vessels, muscles and epithelial structures, binding them together in organs, and filling the interstices of the body.


Mes., Splanchnic mesoderm; Ent., entoderm,. four distinct cells of which are shown at c; V, V, blood vessels containing a few young blood cells.

The origin of the blood and blood vessels remains to be considered. In very early stages the vessels appear as cellular strands, some of which contain a lumen, situated between the mesoderm and entoderm. Associated with these strands, but further out on the yolk-sac, there are clusters or "islands" of blood cells, surrounded by a thin layer of flattened cells known as endothelium. The entire system soon forms a network of distinct vessels situated in the splanchnopleure (Figs. 29 and 32). The formation of this primary vascular network in rabbit embryos has been described by Bremer (Amer. Journ. of Anat., 1912, vol. 13, pp. 111-128). Generally the vessels and the corpuscles within them are! considered to be mesodermal, but some authorities have regarded them as] entodermal, and others have proposed to describe them as forming a separate germ layer or "angioblast" (more appropriately angioderm) .

In the chick embryo shown in Figs. 27 and 28, the network of vessels in the splanchnopleure has formed a complete circulatory system. By a process of folding, portions of the net have been brought together under the fore-gut, where the vessels from the two sides have fused and formed a single median tube, the heart. The two large trunks, derived from the network, which convey the blood from the yolk-sac to the heart are known asjntelline veins^ The heart divides anteriorly into two vessels (the aorta) which pass from the under side of the fore-gut to the upper side, and then extend posteriorly. They finally connect by branches with the network over the yolk, from which they have been derived. Through this system, nutriment taken from the yolk is brought to the heart by the vitelline veins, and distributed throughout the body by the aortae.

In mammals also, a complete system of vessels is established early in development, and it is believed that all later vessels arise as branches of this primary endothelial network. If this opinion is correct, none of the later vessels are formed by the coalescence of mesenchymal spaces, or by transformation of mesenchymal cells into endothelial cells, but only as outgrowths of pre-existing endothelium. There is, however, a very close connection between the endothelium and the surrounding mesenchyma, as shown in Fig. 31.

The histogenesis of the blood is likewise very difficult to follow. The simplest interpretation is one which has not been disproven, namely, that all forms of blood corpuscles are descendants of the cells found in the blood islands of the yolk-sac. According to this hypothesis these cells multiply in certain places to which they have been carried by the circulating blood, for example in the liver in later embryonic life and in the bone marrow of the adult; and they differentiate into the red and white corpuscles of various kinds. The difficulties which this hypothesis encounters will be discussed in later chapters.

The Fundamental Tissues

From the foregoing outline of embryological development, it is clear that all the organs of the body are derived from a relatively small number of fundamental tissues. After the fertilized egg has segmented, it gives rise to layers of cells, of which the ectoderm and entoderm are epithelial from the beginning. The mesoderm very early divides into two tissues epithelium, which lines the body cavity, and mesenchyma, which forms the internal substance of the body wall and intestinal wall. Thus epithelium and mesenchyma may be regarded as the primary tissues of the body. The groups of blood corpuscles, which are probably derived from the mesenchyma, and the endothelium which surrounds them, also arise very early, and these may be set apart as vascular tissue.

The nervous system develops from epithelium, but its cells, singly or in groups, become imbedded in strands and masses of nerve fibers which these same cells send out as processes. Thus little remains in the adult to suggest that the brain or peripheral nerves come from a layer of cells covering a surface, and the nervous system is therefore described as consisting of nervous tissue.

The voluntary muscles are formed from cells derived from the epithelium of the mesodermic somites, but they develop as the somite breaks up and its epithelial character is lost. The involuntary muscles are produced by a transformation of mesenchymal cells into elongated muscle cells. For physiological reasons these two kinds of muscle, which are of diverse origin and structure, are classed together as muscular tissue.

The relation of the germ layers to the five fundamental tissues which have now been recognized, is shown in the following summary.

Origin of the Tissues from the Germ Layers

The ectoderm produces:

1. EPITHELIUM of the following organs: the skin (epidermis) including the cutaneous glands, hair and nails; the cornea and the lens; the external and internal ear; the nasal and oral cavities, including the salivary glands, the enamel of the teeth and anterior lobe of the hypophysis^ the anus; the cavernous and membranous parts of the male urethra; together with that epithelium of the chorion which is toward the uterus and of the amnion which is toward the embryo.

2. NERVOUS TISSUE forming the entire nervous system, central, peripheral and sympathetic.

3. MUSCULAR TISSUE, rarely, as of the sweat glands, and iris. The mesoderm produces:

1. EPITHELIUM of the following four sorts: (i) epithelium of the urogenital organs (except most of the bladder and the urethra) and the epithelioid cords of cells in the suprarenal gland; (2)epithelium of the pericardium, pleurae, and peritoneum and the continuation of this layer over the contiguous surfaces of amnion and chorion; (3) epithelium lining the blood vessels and lymphatic vessels; and (4) epithelium lining the joint cavities and bursae.

2. MUSCULAR TISSUE, striated (voluntary), cardiac, and smooth (involuntary).

3. MESENCHYMA, an embryonic tissue, which forms in the adult, connective and adipose tissue, bone (including the teeth except their enamel), cartilage, tendon, and various special cells.

4. VASCULAR TISSUE, the cells of the blood and lymph, consequently the essential elements of the lymph glands, red bone marrow and spleen.

The entoderm produces:

1. EPITHELIUM of the following organs: the pharynx, including the auditory tube and middle ear, thyreoid and thymus glands; the respiratory tract, including larynx, trachea, and lungs; the digestive tract, including the oesophagus, stomach, small and large intestine, rectum, liver, pancreas, and the yolk-sac; and part of the urinary organs, namely most of the bladder, the female urethra, and prostatic part of the male urethra (including the prostate).

2. NOTOCHORDAL TISSUE, which occurs in the nuclei pulposi.

In the following pages the fundamental tissues will be considered in turn. In connection with them, certain organs will be examined. An 1 organ is a more or less independent portion of the body, having a connective tissue framework, and a special blood, lymph, and nerve supply, in addition to its characteristic essential cells. The essential cellular substance of an organ, in distinction from the accessory tissues, is often called its parenchyma; the accessory supporting tissues constitute the stroma (Gr. arrpupa, bed), in which the parenchyma is imbedded.

Such structures as the pancreas and liver are obviously organs. An individual muscle or a particular bone, which has a connective tissue covering or framework, and a supply of vessels and nerves, besides its essential substance, may also be regarded as an organ. The organs which are of widespread occurrence, such as the bones, muscles, tendons and large vessels, will be described with the tissues. The more complex organs are reserved for a later section, entitled "Special Histology."


The Dutch anatomist, Frederik Ruysch, recognized that the covering of the margin of the lips is not identical with the epidermis. "Therefore," he wrote, "I shall call that covering the epithelis, or papillary integument of the lips" (Thesaurus anat. Ill, 1703, No. 23, p. 26). It is an unfortunate name (CTTI, upon O^Xrj, Latin papilla, the nipple) since it does not refer to the layer upon the nipple, but to that which covers a great number of nipple-like elevations of the underlying tissue. Such elevations or papilla are indeed abundant in the lips, but they occur also under the epidermis. Ruysch substituted epithelia for epithelis in other sections of his work, and Haller, writing some years later, used the neuter epithelium, so that epithelia thus became a plural.

As the term epithelium is now used, it includes the epidermis, and the lining of the various internal tubes and cavities. It has been defined as a layer of closely compacted cells, covering an external or internal surface of the body, having one of its surfaces therefore free, and the other resting on underlying tissue. But the term is also correctly applied to solid outgrowths from such layers, either in the form of cords or masses of cells. Usually these outgrowths subsequently acquire a Cavity, or lumen, around which the cells become arranged in a layer.

The epithelia which cover the skin and line the digestive tube and urogenital organs are thick, as compared with those which line the bodycavity, the vessels, and the synovial cavities. For these thin layers His (1865) introduced the term endothelium. He wrote as follows:

We are accustomed to designate the layers of cells which cover the serous and vascular cavities as epithelia. Jut all the layers of cells which line the cavities within the middle germ layer have so much in common, and from the time of their first appearance differ so materially from those derived from the two peripheral germ layers, that it would be well to distinguish them by a special term either to contrast them, as false epithelia, with the true, or to name them endothelia, thus expressing their relation to the inner surfaces of the body.

The name endothelium, etymologically absurd, has become generally accepted for the lining of the blood vessels and lymphatic vessels. For the other forms of epithelium which it was intended to include, special names have been proposed.

Minot (1890) introduced mesothelium to designate the layer of mesodermal cells which bounds the body cavity. Thus mesothelium does not include the endothelium of the vessels, or the lining of the synovial cavities; but it does include the cells of the nephrotome, through which the body cavity may extend, and also the epithelium which bounds the somites in early stages. Professor Minot applies the term also to the thick epithelium of the renal organs, which is derived from the cells of the nephrotome.

As seen in Fig. 33, the epithelium lining the vessels closely resembles that which lines the body cavities, and to a certain extent this justifies the use of the term endothelium for both layers as proposed by His. But it has been shown embryologically that the vessels and body cavity are of different origin, and are distinct even in the earliest stages. Moreover the linings of the synovial cavities, tendon sheaths, and the chambers of the eye form a third separate group. They arise relatively late in develop- A> Surface view of a ^3i uin from the mesen . ment by the confluence of intercel- * e r r t y B> surface view of endothelium from an lular spaces in the mesenchyma, and they are therefore bounded by flattened mesenchymal cells.

In accordance with these embryological facts, the following use of terms is here proposed:

Endothelium should be restricted to the lining of the blood vessels and lymphatic vessels.

Mesothelium, except in young embryos, should be restricted to the lining of the body cavity and its subdivisions.

Mesenchymal epithelium (or false epithelium) should be applied to the lining of joint cavities and bursae.

All of these forms of epithelium are primarily thin and are derived from the mesoderm. The lining of the body cavity is, however, thickened in places. Thick epithelium may be ectodermal, entodermal or mesodermal in origin.

4 8


Epithelia differ from one another, not only in origin, but also in the shape of their cells, the number of layers of which they are composed, and the differentiation of their cells. These features should be examined in every specimen studied, and something under each heading should be recorded in any complete description of an epithelium.


An epithelium which consists of but one layer of cells is called a simple epithelium, and its cells may be fiat, cuboidal or columnar. These terms refer to the appearance of the cells when cut in a plane perpendicular to the free surface. If in such a section the outlines of the cells are approximately square, as along the upper surface in Fig. 34, the epithelium is cuboidal; if they are stretched out in a thin layer so that they appear linear, as along the lower surface in Fig. 34, the epithelium is flat. Endothelium is an extremely flat epithelium, in which the cells are so thin that the nuclei cause local bulgings of the cell membrane. If the epithelial cells are laterally compressed, so that tall forms result as in Fig. 35, B, the epithelium is columnar. Such epithelium is less accurately called

Cuboidal epithelium.

"' Connective tissue.

Flat epithelium.


above, and amnion below.)

cylindrical, and both cuboidal and flat epithelia are sometimes referred to as pavement epithelium. Intermediate forms, which are described as low columnar or low cuboidal, frequently occur. The cells of certain epithelia change their shape temporarily, as in the bladder during distention, in the oesophagus during deglutition, and, to some extent, in the arteries with every pulsation. During post-mortem contraction the arterial endothelium is considerably thickened. Moreover during embryonic development, epithelial cells may change from one form to another.

On surface view the epithelial cells of all types are polygonal and usually six-sided (Figs. 33 and 35, A). Geometrically a circle would come in contact with six surrounding circles of equal diameter, and a cell is usually in contact with six surrounding cells. The cells, however, vary in diameter, and are often surrounded by five or seven cells and occasionally by four or eight.

An epithelium which consists of several superimposed layers is known as stratified epithelium (Fig. 37). In such cases the basal cells are usually



columnar and closely crowded. They multiply by mitosis and give rise to cells which are pushed toward the free surface. After leaving the basal layer they enlarge and become polygonal in outline. Toward the free surface they become gradually flattened, and may be more or less cornified or transformed into horny material. These scale-like cells are called


A, Surface view; B, vertical section. The prominent cell outlines in A are due to terminal bars, shown in section in B. Cut., cuticular border.



squamous cells and they readily become detached (Fig. 36). Stratified I epithelium is found in the vagina, oesophagus, pharynx and oral cavity ;f and in its most complex form, with many layers, some of which are peculiarly modified, it constitutes the epidermis.

Columnar cells""

Fusiform cells'

..... Basal cells -Conn, tisues.

FIG. 38.


Fig. 39 is a diagram of the condition shown in Fig. 38. X72O.

In certain organs and especially in embryos, simpler forms of stratified epithelium occur, which are described as four-layered, or two-layered as the case may be. The superficial cells may be flat, cuboidal, or columnar. A characteristic epithelium with dome-shaped outer cells and tall basal cells, found in the bladder and ureter, is known as "transitional epithe


Hum" as if it were intermediate between the simple and stratified forms. When the bladder contracts the cells are heaped up in several layers, but when distended the number may be reduced even to two.

If the cell walls are indistinct and the sections are thick or oblique, the number of layers in an epithelium may be very difficult to determine. Thus in a simple epithelium the nuclei may be at different levels (Fig. 35, B), and if the section is not vertical it will show several layers, approaching the condition of the tangential section, Fig. 35, A. Fig. 38 represents a vertical section of an epithelium with nuclei at three levels, and in two forms (the basal nuclei being round and the others elongated) ; but yet, as interpreted in Fig. 39, it is not stratified. It is of the form known as pseudo-stratified, in which all the cells reach the underlying connective tissue, but only a limited number extend to the free surface. Pseudo-stratified epithelium occurs in the upper part of the respiratory tract, including the trachea and larger bronchi, and in the epididymis.


Free surface. The free surface of epithelial cells is often provided with a thickened top-plate or cuticula. Under high magnification the cuticular border of the columnar cells in the intestine is seen to be vertically striated (Fig. 35, B), and these striations have been interpreted as minute canals through which protoplasmic processes may be sent out beyond the free surface. In some cases, however, the striated cuticula appears to consist merely of short, parallel protoplasmic rods. In certain cells of the kidney, the rods may become somewhat divergent, giving rise to what is known as the "brush border." Longer processes, which are vibratile but not retractile, are called cilia (the Latin term for eyelashes). They project from the free surface of certain epithelial cells in the trachea and bronchi (Figs. 38 and 39), in the uterus and uterine tube, in the efferent ducts of the testis, and in the nasal part of the pharynx together with the auditory tube and naso-lachrymal duct which open into it. In the living condition the motion of cilia may be observed in various unicellular animals. It may be studied advantageously in fragments from the margin of the gills of a clam, or in epithelium from the roof of the mouth of a frog. The cilia are numerous, and in the snail Heidenhain counted no arising from a single cell. They do not act together, but rapidly succeeding waves, due to the bending of the cilia, pass over the entire surface. By bending sharply downward, each cilium creates a forward current in the overlying fluid, and passes the particles above it to the cilium in front. No sooner does a cilium begin to bend than the next in front takes up the movement and thus the ciliary waves are propagated. In some animals, however, the wave proceeds


in a direction opposite to that of the effective stroke. The cilia in man produce currents toward the outlets of the body. In the uterine tube the stroke is toward the uterus, presumably favoring the passage of the ova, but the spermatozoa ascend this tube against the current.

The structure of cilia, because of their small size, is difficult to determine, but in many cases a differentiation between the exoplasm and endoplasm has been observed. The simplest cilia, as shown in the diagram (Fig. 40, a), are essentially permanent pseudopodia, with contractile sheaths and fluid contents. They may develop very rapidly in the protozoa. Thus Prowazek has seen processes grow out in eight minutes, which were then vibrating 19 times in 20 seconds. Schafer

PIG. 40.

a, b, c, Diagrams to illustrate the structure of cilia. (After Williams.)

FIG. 41.

Diagram of a ciliated cell (after Prenant) , showing yibratile cilia; b, cells of the human epididymis (after Fuchs), showing non-motile cilia.

considers that cilia are primarily pseudopodia, and that their motion is caused by the alternating ingress and egress of fluid to and from the central part, due to variations in the surface tension.

Many cilia, however, appear to contain more or less solid axial rods, which generally proceed from round basal bodies resembling centrosomes. That these bodies arise from the centrosome has recently been denied. Sometimes the bodies are double, and extensions from them downward into the cytoplasm may occasionally be observed (Fig. 41, a). These roots approach one another beside the nucleus, and it has been discussed whether or not they unite. The roots, and portions of the cytoplasmic reticulum at right angles to the shafts of the cilia, have been thought to act as levers. Others conjecture that the central shaft is a supporting structure, perhaps elastic, which is surrounded by a contractile sheath. The contractile elements may extend the whole length of the cilium or be ' confined to its base, as indicated in the diagram (Fig. 40, b and c). If


the sheath were equally developed about the entire circumference of the axis, the cilia should be able to strike in any direction. Usually the effective stroke is in one direction only, but in some cases it may be reversed. In reversible cilia, such as occur on the labia of the sea anemone, the effective stroke is either toward the mouth or away from it, according to the chemical composition of the substances in contact with the cilia (Parker, Amer. Journ. of Physiol., 1905, vol. 3, pp. 1-16). In such a case the contractile material is supposed to be gathered in two bands, on opposite sides of each cilium. In the irreversible cilia, such as are found elsewhere in the sea anemone and in man, the contractile material, according to Parker, must be gathered especially on one side of the supporting axis.

The whip-like processes, or flagella, which form the tails of spermatozoa, may be compared with single cilia. Each springs from a body resembling a centrosome, and consists of an axial filament with a surrounding sheath, but whether the filament or the sheath contains the contractile substance is still uncertain.

Non-motile projections, somewhat resembling cilia, are found in the cells of the epididymis (Fig. 41, b). They have no basal bodies, and lack the distinctness of true cilia. Generally they appear in conical clumps, which have been compared to the hairs of a wet paint brush. They may be concerned with the discharge of secretion. Other nonmotile processes of epithelial cells are the tapering projections of the sensory cells, apparently designed to receive stimuli. The lining of the central cavity of the spinal cord and ventricles of the brain is also provided with short projections, which may be degenerating cilia. It is questionable whether these are motile.

Lateral surface. The lateral surfaces of epithelial cells may be in close contact with one another, sometimes without intervening cell walls; or they may be separated by

a thin layer of intercellular substance, which is generally fluid. Immediately beneath the cuticular border of the cells lining the intestine, the intercellular substance takes the form of a more solid bar encircling each cell and binding it to those which surround it. The arrangement of these terminal bars is shown in the diagram, Fig. 42, and in the section Fig. 35, b. If the section passes down through the

IntercellU' lar substance.

PIG. 42. DIAGRAM OF THE NETWORK OF TERMINAL BARS. The two cells on the left are divided lengthwise

into halves; the two on the right are drawn

as complete cylinders or prisms.



middle of the cell, as on the left of Fig. 35, b, the bars are cut across and appear as points; but if either the proximal or distal side of the cell is included in the section, they appear as lines, as on the right of the figure. Terminal bars have been found in many epithelia, especially in mucous membranes and glands. They occur in the epididymis (Fig. 41, b) where they appear as thickenings of the cell wall. According to Stohr they are found in the stratified epithelium of the tongue and bladder.

The intercellular substance in endothelium and mesothelium is ordinarily inconspicuous, but it may be demonstrated by treating the tissue with a solution of silver nitrate. The resulting precipitate occurs chiefly in the intercellular "cement substance," which then appears as a wavy black line bounding each cell (Fig. 33). It is of importance since various forms of blood corpuscles make their way through it from the vessels into the surrounding tissue.

In the lower layers of the epidermis and the thick oral epithelium, the intercellular substance is clearly seen, and here it is bridged by spiny processes from the adjacent cells. These intercellular bridges occur in endothelium and many forms of epithelium, but they are most readily observed in the deep layers of the thick stratified epithelia (Fig. 43). Within the bridges, fibrils pass from cell to cell. In the intercellular spaces between the spiny processes, nutrient fluid makes its way to the outer layers. Whatever nutriment they receive must be derived from the intercellular fluid or DE S . F THE EPI * through the bodies of the underlying cells, since neither blood vessels nor lymphatic vessels penetrate the epithelium. This is probably true of all epithelia in man, but in the bladder and renal pelvis the blood vessels approach very close and may appear to enter, and in the amphibia, according to Maurer, capillaries may be observed well within the oral epithelium. Nerve fibers extend among the basal cells of the epidermis and other epithelia, and ramify in contact with these cells, but special methods are required to demonstrate them.

Basal surface. The basal cells of an epithelium sometimes seem to send out processes which blend with the underlying connective tissue. Usually, however, the lower surface is well defined, and the epithelium is bound down by intercellular cement substance. Often, especially in glands, the epithelium rests upon a thin, well-defined basement membrane or membrana propria. This membrane is usually homogeneous and contains very few nuclei. Sometimes it is composed of elastic tissue. Certain basement membranes have been considered as derivatives of the epithelium, but generally they are clearly of mesenchymal origin.



Many epithelial cells elaborate and discharge substances which do not become parts of the tissue. Such cells are called gland cells, and their products are either utilized by the body (secretions) or eliminated as waste products (excretions). The process of elaboration and discharge of the secretion or excretion may often be recognized by changes in the form and contents of the cell. A gland cell which is full of secretion, or discharging it, is called "active," and one in which the secretion is not apparent, though it may be in process of formation, is called "resting." The appearances during secretion differ in two types of gland cells the serous, which produce watery secretions, like saliva; and the mucous, which form thick secretions, like those of the nose and throat. These will be considered in turn.

Serous gland cells, when empty, are small and darkly staining. As


.-,, ..^-^~- l r, , -...* * ^ ' New granule.

Basal filaments.



Large nucleolus. A B

FIG. 44. Two SEROUS GLAND-CELLS FROM THE SUBMAXILLARY GLAND OF A GUINEA-PIG. X 1260. In cell B the granules have passed into the unstainable state; new stainable granules are beginning to

develop in the protoplasm.

the formation of secretion begins, the cells, if prepared with special methods, exhibit granules which stain intensely. These granules have become cut off from the basal filaments or mitochondria (Fig. 44, A). They enlarge, lose their staining capacity, and are transformed into drops of secretion. The entire cell becomes larger and clearer than before, and the alveolar structure of its protoplasm is well marked (Fig. 44, B). Finally the droplets become confluent and are discharged from the free surface of the cell. A portion of the mitochondria remains behind as the source of further secretion. In many gland cells the cytoplasmic differentiation is accompanied by changes in the nucleus. In the empty cell the nucleus has distinct nucleoli and a fine chromatic reticulum, but in cells full of secretion the nucleoli have enlarged or disappeared and the chromatin is in the form of coarse masses. Particles pass from the nucleus into the cytoplasm, and these have been said to give rise to secretory granules.

In mucous cells the process of secretion also begins with granule formation, but the mucigen granules gather near the free surface of the cell



FIG. 45. EPITHELIAL CELLS SECRETING Mucus. From a section of the mucous membrane of the human stomach Xs6o. p, Protoplasm; s, secretion; a, three cells, two empty, the third showing the beginning of mucoid metamorphosis; e, the cell on the right is discharging its contents; the granular protoplasm has increased and the nucleus has become round again.

where they become changed into clear droplets of mucus. A discoid mass of secretion is thus produced which is quite sharply marked off from the underlying cytoplasm (Fig. 45, a and b). As the cytoplasm becomes increasingly transformed into secretion, the elongated nucleus becomes at first round, and then flattened. It is forced to the base of the cell where it is lodged in a small amount of unchanged cytoplasm (Fig. 45, b-d). The secretion is then gradually discharged through the distended topplate, which is often ruptured in sections, and the nucleus again becomes

round and moves toward the center of the cell. Most gland cells are not destroyed by the act of secretion, but may repeat the process several times. An exception occurs in the case of the sebaceous glands, in which the cells disintegrate and are cast off with their products. In the mucous cells of the intestine, secretion is formed below and discharged from the free surface at the same time. The cells, as seen in Fig. 46, arise near the bottom of tubular depressions lined with simple columnar epithelium. By the formation of new cells below them they are pushed toward the outlet of the tube. Thus the youngest cells are at the bottom of the pit and the oldest are at the top. For a time the secretion develops faster than it is discharged, and the cells enlarge as seen in the middle part of the gland; later, as elimination exceeds production, they become narrow, and their final stages, as compressed cells with

Gland lumen.


HUMAN LARGE INTESTINE. X 165. The secretion formed in the goblet-cells is here colored blue; usually it is pale as in Fig. 45. In zone I the goblet-cells show the beginning of secretion; that expulsion has begun is evident from the presence of drops of secretion in the lumen of the gland. 2, Goblet-cells with much secretion. _ 3, Goblet-cells containing less secretion. 4, Dying goblet-cells, some of which still contain remnants of secretion.


a remnant of secretion, are found near the orifice of the gland. Cells such as have been described, which appear like cups filled with mucus, are known as goblet cells.

In certain stratified or pseudo-stratified epithelia, the formation of mucus has been seen to take place in some of the deeper cells, but the discharge of the secretion can occur only when these cells have reached the free surface.


The simplest form of gland is merely a single secreting cell situated apart by itself in an epithelium. Such unicellular glands are abundant in invertebrates and are represented in man by scattered goblet cells. In the higher animals the secreting cells usually occur in groups, and they are generally found in tubular or saccular outpocketings of the epithelium.

Excretory duct.

Secretory duct.

Intercalated duct

End pieces.

FIG. 47. DIAGRAM OF VARIOUS FORMS OF GLANDS. The arrangement of ducts in D is that of the human submaxillary gland.

An unbranched tubular gland is shown in vertical section in Fig. 46, and in the diagram, Fig. 47, A. The secreting cells may be distributed throughout the tube, or they may be limited to the lower part. In such cases the upper part forms the duct of the gland. Sweat glands are unbranched tubes, with a coiled secreting portion in the deeper part of the skin, and a relatively long duct which conveys the secretion to the surface. Many glands are branched, as in Fig. 47, B. The main stem becomes the duct, and the characteristic secretion is formed in saccular or tubular " end pieces."


Such glands as have been described, either branched or unbranched, occur in great numbers as constituent parts of some organ, and they are classed as simple glands. The sebaceous and sweat glands of the skin, intestinal glands, and uterine glands are examples of this class. Many glands are much larger than these, owing to the fact that the epithelial outgrowth has branched repeatedly. It becomes invested with a connective tissue capsule, which sends partitions, or septa, among the ramifications of the epithelial tube, thus dividing the gland into lobes and lobules. A lobule usually contains a terminal branch of the duct together with the cluster of end pieces which empty into it. The large glands not only have a connective tissue framework, but also a special supply of nerves, blood vessels and lymphatic vessels. Thus they form independent organs, and they are classed as compound glands. They include the liver, which discharges its secretion through a single duct; the pancreas, which is formed by the fusion of two glands and therefore has primarily two ducts; and many smaller organs, like the prostate, which is a compact group of glands each of which has a separate duct.

All the glands thus far considered are alike in being outpocketings of epithelium. Most of them develop as masses or cords of epithelial cells which later acquire a central cavity or lumen. The secreting cells may discharge their products from their free surfaces directly into the lumen; or the secretion may enter minute

canals, either within the cells (intracellular), or FlG< 48 ._Di7^A^F A SIMPLE ALbetween the cells (intercellular). Intercellular secretory canals (also called capillaries) are

found in the serous glands of the tongue and

in the serous portions of the salivary glands; they occur also in the liver, the gastric and pyloric glands, sweat glands, lachrymal gland and bulbo-urethral gland. Various forms are shown in the right half of the diagram Fig. 48. They occur where two or more cells come together and consequently they are in relation with two or more terminal bars. In longitudinal sections the bars may be seen to extend downward along the canals. Through such intercellular canals the basal cells in a glandular epithelium may discharge their secretion into the central cavity, as shown in Fig. 48. Intracellular secretory canals, shown in the left half of Fig. 48, are less definite in outline, and are never in relation with terminal bars. They may be transient vacuoles opening at the surface. Sometimes they anastomose and form a network of canals within the cell. They have been observed, together with intercellular canals, in the sweat


glands, the liver, and the gastric glands. There are apparently no secretory canals in any mucous gland, and they have not been found in the duodenal, intestinal, uterine and thyreoid glands, the kidney or the hypophysis.

The ducts have a clear-cut lumen and are typically lined with a very regular epithelium, showing distinct cell boundaries. The cells usually do not contain the rods, granules or vacuoles characteristic of secreting protoplasm, and the nuclei are not crowded to the base of the cells. In some cases, however, the ducts contain mucous cells, and in the salivary glands a specialized portion of the ducts is believed to discharge salts into the secretion as it passes through them. In such a gland (Fig. 47, D) the duct, as it leaves the end pieces, consists of simple flat epithelium. This intercalated duct gives place to the secretory duct which is lined with columnar epithelium, having basal rows of granules. The outer excretory portion consists of simple or stratified non-glandular epithelium.

The end pieces of the glands, as already noted, vary in shape from saccular to tubular. Usually a minute dissection or a reconstruction is necessary to determine what the shape may be. A round termination is called an acinus (Latin, a grape or berry) or an alveolus (Latin, a trough or tray). These terms are often used interchangeably. The elongated forms are called tubules.

During the development of the thyreoid gland the duct becomes obliterated, so that the secretion within the end pieces cannot escape. The end pieces become closed epithelial sacs, known as follicles (Latin, folliculus, a leather bag, shell, or husk). In addition to the material enclosed within the follicles, the thyreoid gland secretes substances which are taken up by the surrounding blood vessels and lymphatic vessels. Secretions of this sort are called internal secretions.

The epithelioid glands are masses or cords of cells which produce internal secretions only. They are never provided with a duct or lumen, although in some cases their cells arise from the wall of an epithelial tube. They are closely related to the glands with obliterated ducts.

Finally there are glands which produce cells and are therefore called cytogenic glands. These include the ovary and testis, which are epithelial structures consisting of follicles and tubules respectively. They produce the ova and spermatozoa. The other cytogenic glands are non-epithelial bodies which produce various forms of blood corpuscles. They will be considered in a later chapter.

The classification of glands, as presented in the preceding paragraphs, is summarized in the following table:



I. Epithelial glands, with persistent ducts, producing external secretions.

1. Unicellular glands.

2. Simple glands.

a. Ectodermal, e.g., sweat and sebaceous glands.

b. Mesodermal, e.g., uterine glands.

c. Entodermal, e.g., gastric and intestinal glands.

3. Compound glands.

a. Ectodermal, e.g., mammary and lachrymal glands.

b. Mesodermal, e.g., epididymis and kidney.

c. Entodermal, e.g., pancreas and liver.

II. Epithelial glands, with obliterated ducts, producing internal secretions.

a. Ectodermal, anterior lobe of the hypophysis (the duct of the

posterior lobe is partially obliterated).

b. Entodermal, thyreoid gland.

III. Epithelioid glands, never having duct or lumen, producing internal secretions. .

a. Ectodermal (through their relation to the sympathetic nerves),

chromaffin bodies; and medulla of the suprarenal gland.

b. Mesodermal, cortex of suprarenal gland; interstitial cells of

the testis; corpus luteum.

c. Entodermal, islands of the pancreas; epithelioid bodies in

relation with the thyreoid gland; thymus (?)

IV. Cytogenic glands, producing cells.

a. Mesodermal, epithelial the ovary and testis.

b. Mesodermal, mesenchymal the lymph glands, haemolymph glands, spleen, red bone marrow, and many smaller lymphoid structures.

The Mesenchymal Tissues

Mesenchyma (/wos middle, trxyf^, an infusion) is a term introduced by O. Hertwig, in 1883, for the tissue produced by cells which have wandered out from the epithelial germ layers into the spaces between them. It is found only in young embryos. In the adult it is represented by a large group of derivatives, including connective tissue, adipose tissue, cartilage, bone, smooth muscle fibers, tendons, fasciae, and various special forms of cells. Mesenchyma arises chiefly from different parts of the mesoderm, as already described (p. 42), but in the head of the chick embryo a portion of it comes from the ectoderm, and in the wall of the intestinal tube, according to Hertwig, the entoderm contributes to its formation. Together with the blood islands it constitutes the entire non-epithelial tissue of the embryo in early stages. It consists of a network of branching cells, in the meshes of which there is a homogeneous, fluid, intercellular substance. The intercellular portion of the tissue becomes highly developed and variously modified.

Although typical epithelium and mesenchyma are radically different, as shown in Fig. 31, p. 42, there are conditions in which they are comparable. Thus dense mesenchyma, in which the cells are closely packed and have very little intercellular substance, resembles epithelium, and it may give rise to groups or cords of epithelioid cells. Moreover epithelium may resemble mesenchyma by forming a vacuolated syncytium, or as seen in Fig. 49, a branching protoplasmic network. In epithelium the intercellular spaces arise as vacuoles in the exoplasm, and the intercellular substance of mesenchyma may also be considered as occupying coalescent vacuoles.


The tissue of the adult which most closely resembles mesenchyma is known as reticular tissue. It cannot, however, be regarded as an immature connective tissue, or a persistence of the primitive mesenchyma, since it arises rather late in embryonic development (e.g., in the lymph glands which first appear hi human embryos measuring about 45 mm., and in the oesophagus of embryos of 30 mm.). It is therefore considered to be a special form of connective tissue.

Reticular Tissue

Reticular tissue forms the framework of lymph glands, red bone marrow and the spleen; it occurs as a layer immediately beneath the epithelium of the digestive tract, and has been reported in many other organs. It consists of a network of cells in relation with an abundant



fluid intercellular substance (Fig. 50). The protoplasmic processes of the primitive mesenchyma have become transformed into flattened strands or slender fibers, which are clear and homogeneous, and anastomose ? freely. The cells associated with these fibers contain pale," flattened, oval nuclei, with few chromatin granules. In ordinary sections reticular tissue will be most readily recognized by the cells lodged in the fluid intercellular substance. These cells, which are chiefly lymphocytes, having round nuclei and a narrow rim of protoplasm, are often so abundant that the tissue appears as a dense cellular mass in which the framework of reticular tissue is almost completely hidden. Upon careful examination, however, some of its nuclei and fibers can always be detected.


In order to study reticular tissue advantageously, the lymphocytes and other forms of free cells should be disengaged from its meshes. This may be accomplished by shaking or brushing the sections; or by artificially digesting the specimen (which if properly done will destroy the cells, including those of the reticular tissue, but will leave the network of fibers); or by the following ingenious method devised by Mall. A piece of fresh spleen is distended by injecting gelatin into its substance; it is then frozen and sectioned. The sections are put in warm water, which dissolves out the gelatin, carrying the loose cells with it, and leaves areas of clear reticular tissue. Professor Mall has also shown how to wash out the


pulpy contents of the entire spleen, so as to leave the framework of connective and recticular tissue, which may be inflated and dried (Zeitscbr. f. Morph., 1900, vol. 2, pp. 1-42). Such preparations give an idea of the intricacy of the reticular meshwork that can be obtained in no other way, and yet the finer ramifications have been destroyed by this process.

There has been considerable discussion as to whether the fibers of reticular tissue are chemically different from those of ordinary connective tissue. They differ from the elastic elements of connective tissue, since reticular fibers are dissolved by both acids and alkalis which leave the elastic fibers intact; and they are not destroyed by pancreatic digestion which causes the elastic fibers to disintegrate. But the differentiation of the reticular fibers from the "white fibers" of connective tissue has not been successfully accomplished. Mall has shown, however, that tendon, consisting largely of white fibers, is dissolved more readily by boiling in p.c. solutions of potassium hydrate or hydrochloric acid, respectively, than sections of lymph glands; and the name reticulin has been introduced for a constituent of the reticular fibers which does not yield gelatin on boiling. Reticulin is not generally recognized as an independent substance, and reticular tissue often appears to blend with white fibrous connective tissue. The recognition of reticular tissue depends, therefore, on its form rather than on its chemical constitution.

Mucous Tissue

The substance of the umbilical cord is composed of mucous tissue. At birth it is a peculiar gelatinous mass of pearly luster, which has long been known anatomically as Wharton's jelly. During its development from mesenchyma, a large amount of mucus becomes deposited in its intercellular spaces. This mucus, like that produced in the goblet cells and that found in the cornea and vitreous body of the eye, is a translucent substance which contains mucin. Chemically there are many (varieties of mucins. They are compound protein bodies containing a 'carbohydrate complex in their molecules, and are therefore known as glycoproteins. True mucins are formed in abundance in goblet cells and in mucous tissue; to a less extent they occur in all embryonic connective tissue. Related substances, called mucoids, have been obtained from tendon, cartilage and bone.

In the umbilical cord the mucus may be regarded as a secretion which is produced without the formation of special granules or vacuoles, and is discharged equally from all surfaces of the cells. It is a homogeneous ground-substance, in which extremely delicate fibrils are imbedded. These are gathered in wavy bundles (Fig. 51, a). Fibrils of the same sort, generally arranged in denser bundles, are found in ordinary connective tissue, and constitute the white fibers. Chemically they are said to consist of collagen, an albuminoid body which on boiling yields gelatin, the source of glue. The origin of the collagenous fibers has been the subject of repeated investigation. Henle (1841) considered that they arose in the intercellular substance, apart from the cells, and Merkel defends this idea in the following passage, here somewhat abbreviated (Anat. Hefte, Abt. i, 1909, vol. 38, pp. 323-392):

The mesenchymal syncytium secretes an amorphous gelatinous substance, which may be scanty (as in reticular tissue) or abundant (as in the umbilical cord) . The fibers arise exclusively in this gelatinous substance; the cells take no direct part in the formation of the fibers but serve only for the production of the jelly. At their first appearance the fibers are not collagen, and generally they are not yet smooth and glistening like true connective tissue fibers. Instead they are granular, and not infrequently varicose. Later, though often very soon, they acquire the characteristic appearance of fully


H*MATOXYLIN. (Mallory.) a, White fiber, b, fibroglia.

formed connective tissue fibers. They may arise as a very delicate network, which, through the breaking down of the least utilized threads, becomes transformed into smooth and unbranched fibers. But in places where from the first there is a decided stretching, as in tendon, parallel unbranched fibers are formed directly. Professor Heiderich has shown me preparations of a mucin, in which, by the addition of acid, structures were formed which were strikingly similar to developing connective tissue without any stretching, nets with round meshes; but with the slightest traction, long fibers isolated from one another. Thus connective tissue fibers are merely the effects of mechanical conditions upon the gelatinous intercellular substance.

A very different idea of the origin of the white fibers is that of Flemming, recently further elaborated by Meves (Arch. f. mikr. Anat., 1910, vol. 75, pp. 149-208), according to whom the fibers arise within the cytoplasm. By special methods Meves has demonstrated coarse filaments, which he names chondrioconta, within the protoplasm of both epithelium and mesenchyma. These granule-rods or chondrioconta (probably comparable with the mitochondria of gland cells) are regarded as a part of the fundamental protoplasmic network or spongioplasm. If they are short they are called chondriosomes. Meves describes the development of white fibers as follows:

Connective tissue fibrils are produced from the chondrioconta which come to lie at the surface of the cell. They then change their chemical constitution and are no longer stained by iron haematoxylin or fuchsin. At this stage those which are in a row unite end to end. Thus in the formation of a fibril numerous cells take part, each producing a section. The fibrils again change their chemical constitution and become intensely stained by the collagen stains. Finally they become free from the cells and lie in the intercellular spaces. From the time of their first formation they have a wavy course, which may become more marked later. This clearly means that the connective tissue fibers have grown in length more than the surrounding elements. They increase also in diameter through independent growth, and for a time new fibers are produced by the cells I differ with Flemming since I consider that connective tissue fibers are not formed within the cell body but are produced at the cell surface (by transformia tion of the chondrioconta) ; I agree with him in deriving them from the cytoplasmcfilaments.

The umbilical cord "has long been regarded as a particularly favorable object for the study of white fibers, but the way in which they arise remains undetermined. In addition to these white fibers, the umbilical cord contains stiff fibers of a different nature, found at the periphery of the cells. They are similar to the fibers of a tissue which forms the framework for the branching nerve cells, thus binding them together, and accordingly named neuroglia (vevpov, nerve, y\ta, glue). Fibers similar to those of the neuroglia, found at the periphery of muscle cells, are called border fibrils or myoglia. In 1903 Mallory described similar border fibrils in connective tissue and named them fibroglia. They are seen at the periphery of the cells in the umbilical cord (Fig. 51, b). Mallory describes them as follows (Journ. Med. Res., 1905, vol. 13, pp. 113-136):

Neuroglia, myoglia and fibroglia fibrils morphologically and in certain staining reactions more or less closely resemble one another. They touch or form part of the periphery of the cell protoplasm, but continue away from the cell in two directions, *.., they do not begin or end in the cell which produces them. How far the fibroglia are accompanied by protoplasmic processes cannot be determined. The number of these fibrils to a cell is not constant, but it is usually in the neighborhood of a dozen.

Professor Mallory has found no transitions between the fibroglia and the white fibers. Meves likewise considers them as entirely distinct, and states that the production of white fibers by the cells of the umbilical cord terminates by the fifth month. The fibroglia are present at birth, and probably no tissue is more favorable for their study than the umbilical cord at term.

In addition to the mucous matrix, the white fibers, and the fibroglia, mucous tissue contains cells and intercellular spaces. The cells, at first stellate with many anastomoses, become elongated and more or less disconnected from one another. Three of their nuclei are shown in Fig. 51, but their cytoplasm forms a thin layer, the limits of which can scarcely be determined. The intercellular spaces contain a fluid through which cells may migrate. There are no capillaries, lymphatic vessels, or nerves within the mucous tissue of the umbilical cord, and no elastic fibers. The three large blood vessels which pass through the cord, and the tissue in their walls, will be considered later.

Connective Tissue

Connective tissue occurs in various forms. Dense connective tissue is a tough fibrous substance, such as that part of the skin from which leather is made; and loose connective tissue, or areolar tissue, is a spongy cobweb of delicate filaments, such as occurs between the muscles. Both forms when fresh are very white, and they are composed of similar fibers. A small mass of fresh connective tissue, subcutaneous or inter-muscular, may be spread out with needles upon a slide, thus forming a thin film. After adding a drop of water and applying a cover glass, it will present such an appearance as shown in Fig. 52. The bulk of the tissue is seen to consist of white or collagenous fibers felted together (Fig. 52, c). They are the same in origin and structure as those already described in the mucous tissue of the umbilical cord, but in ordinary connective tissue their fibrils are gathered into denser bundles. Each bundle or fiber is composed of exceedingly minute fibrils, bound together by a small amount of cement substance. The addition of picric acid causes the fibers to separate into their constituent elements. Often a bundle of fibrils turns aside from the main trunk, so that the fiber branches, but the fibrils themselves are unbranched.


The fiber a has been treated with dilute acetic acid; the other fibers have been teased apart and examined, unstained, in water, a, c, White fibers; b, fat cell; d, connective tissue cell; e, elastic fibers.

Upon the addition of dilute acetic acid the white fibers swell and disintegrate, some of them passing through the condition shown in Fig. 52, a. Such fibers show a succession of constrictions at places where they are encircled by rings or spiral bands of a refractive substance not affected by the acid. These rings have been observed by Ranvier in living connective tissue fibers, and it is therefore improbable that they are remnants of a sheath which surrounded the entire fiber, as some have thought. They are probably formed of elastic substance.

In addition to the white or collagenous fibers, connective tissue contains fibers of a second sort, known as elastic fibers.' They are absent from corneal tissue, the mucous tissue of the umbilical cord and generally, though not always, from reticular tissue. Since they develop later than the white fibers, they are not found in young connective tissue; but otherwise they are present, though varying greatly in abundance, in all forms of connective tissue. They are not destroyed^

by dilute acids or alkalies, and are described as composed of elastin, an albuminoid body which does not vieldjrelatin on boiling. Unlike the white fibers they are not composed of smaller elements or fibrils, but each fiber is a structureless homogeneous thread. In favorable cases, however, an enveloping sheath may be seen. In tissue which has not been torn apart the elastic fibers form a net (Fig. 53, A). The fibers meet and fuse with one another; and across the angles thus formed, one or two delicate strands are commonly to be found. When the tissue is pulled apart so that the net is broken, the fibers kink and recoil like tense wires (Fig. 52, e).

The origin of the elastic fibers has not been determined. They have been said to arise within the cells by the fusion of granules of elastin. Mall's idea of their exoplasmic origin is illustrated by their relation to the cells in Fig. 53, B. Others consider that they are formed from the intercellular substance.

Although elastic fibers are clearly seen in fresh connective tissue, they are often invisible in specimens stained with haematoxylin and eosin. In order to determine their presence, sections may be stained with resorcin-fuchsin, which leaves the white fibers nearly colorless, but makes the elastic fibers dark purple; or other special stains may be used. In some situations, however, the elastic tissue is highly developed and may be seen with any stain. This is true of the fenestrated membranes found in many blood vessels. A fenestrated membrane is a network of elastic fibers in which the fibers are so broad that they appear to form a perforated plate (Fig. 54, A). The greatest development of elastic tissue probably occurs in the ligament of the neck in grazing animals, which consists of very coarse elastic fibers with very little white fiber. It is therefore commonly used for the histological and chemical study of elastic tissue (Fig. 54, B and C). In man the stylohyoid ligament and the ligamenta flava are of this class, and they exhibit the yellowish color which is characteristic of elastic tissue. Elastic fibers are found also in the ground substance of certain cartilages, which will be described later.

FIG. S3.

A, Elastic fibers of the subcutaneous areolar tissue of a rabbit. (After Schafer.) B, Cells in relation with elastic fibers, after treatment with acetic acid. Subcutaneous tissue of a pig embryo. (After Mall.)

Connective Tissue Cells. In addition to white collagenous fibers and yellow elastic fibers, connective tissue contains cells and intercellular spaces. The cells which produce fibers are known as fibroblasts (/JAao-ros, a bud, is used in many terms to indicate a formative cell, with a prefix which usually designates the structure which it produces). Actively


A, Network of thick elastic fibers below, passing into a fenestrated membrane above. From the human endocardium. B, Thick elastic fibers (f) from the ligamentum nuchae of the ox; b, white fibers.^C, Cross section of the ligamentum nuchae, lettered as in B.

growing fibroblasts, both in the embryo and in the adult, exhibit fibroglia fibrils at their borders, but in mature connective tissue these fibrils are seldom found. The cells of fully formed connective tissue are generally flattened or lamellar, consisting of a thin pale layer of almost homogeneous protoplasm, which is sometimes vacuolated. Such cells when seen on edge are spindle-shaped. They may be spread out in flat layers, retaining the protoplasmic connections characteristic of mesenchyma, as seen in the mesentery (Fig. 55, c). In dense connective tissue the cells also exhibit broad thin protoplasmic processes (Fig. 56, c), but they have become more or less detached from one another. The cells are bent to conform with the adjacent fibers, to which they are closely applied, and along which, in living tissue, they have been observed to migrate. The nuclei of these cells are elliptical on surface view, and rod-shaped when seen on edge. They contain fine chromatin granules, and sometimes a small but distinct nucleolus. Occasionally the nuclei are indented on one side. The centrosome, in a clear area of protoplasm, has been found close beside the nucleus. In ordinary specimens, stained with haematoxylin and eosin, the centrosome is not seen, and the entire cytoplasm is quite inconspicuous; but the nuclei stand out prominently along the edges of the fibers (Fig. 56, x).

FIG. 55. CONNECTIVE TISSUE CELLS (c) AND A MAST CELL (m )FROM THE MESENTERY OF A RAT. X 1000; b.v. a small blood vessel lined with endothelial cells. The specimen was fixed in alcohol and stained with Unna's methylene blue.

Fig. 56. CONNECTIVE TISSUE CELLS (c) A LYMPHOCYTE 0) AND PLASMA CELLS (p) FROM A LACTATING HUMAN BREAST. X 1000. A vacuolated plasma cell is shown at v, and a connective tissue cell on edge is seen at x.

Cells in connective tissue which differ from the fibroblasts by having abundant protoplasm in the form of large round cell bodies, were named plasma cells by Waldeyer (Arch. f. mikr. Anat., 1875, vol. n, pp. 176194). He stated that they develop from connective tissue cells, and are always arranged about the blood vessels. Two years later, in the same journal, Ehrlich published the first of his far-reaching investigations on the effects of various anilin dyes upon protoplasm. He showed that the plasma cells found near the vessels in the mesentery of the rat, when stained with basic dyes, exhibit very coarsely granular protoplasm (Fig. 55, m). Further studies led him to separate these granular cells from the other forms of plasma cells. He was inclined to believe that they arose from over-nourished connective tissue cells, and accordingly named them mast cells (Mastzellen), referring to the mast or acorns on which animals are fattened (Arch. f. Physiol., 1879, pp. 166-171). In another communication in the same volume (pp. 571-579), he introduced a further subdivision of cells which may be alike in form but which react differently to the anilin dyes. In contrast with the basic granules of the mast cells, which are not stained with the acid dye eosin, he found other granules which stain deeply with eosin but do not respond to the basic dyes. These granules are now generally known as eosinorjhjHCi and the cells which contain them are called eosinophiles. Mast cell granules are often referred to as basophilic, but since some confusion results from calling the entire cells basophiles, they are still known as mast cells. Cells of both classes are found in the circulating blood, and will be described with the blood corpuscles; both kinds are found also in the intercellular spaces of connective tissue. It is known that various forms of blood corpuscles develop in the reticular tissue of lymph glands and bone marrow, from which they enter the blood vessels; and it is also very evident that cells leave the vessels and enter the intercellular spaces of connective tissue. There has been endless discussion as to whether the eosinophiles of connective tissue and blood are the same sort of cell; and also whether the "mast leucocytes" in the vessels and the mast cells in the surrounding tissue are identical. Maximow states that there is no genetic relation between mast cells and mast leucocytes in the adult, but "whether in embryonic life they are likewise independent is still undecided." As to the eosinophiles, he says: Those found in the connective tissue are generally eosinophilic corpuscles which have emigrated from the vessels. "Any proof of a local origin in connective tissue is lacking." But Weidenreich considers that eosinophilic granules are derived from broken-down red corpuscles, which are taken up by white blood corpuscles and by connective tissue cells, both of which become thereby eosinophilic.

In ordinary sections of connective tissue, stained with haematoxylin and eosin, eosinophiles are seldom overlooked, because of the brilliant color of their granules. Mast cells, however, should be sought for in tissue preserved either in formalin or alcohol, and stained with Unna's polychrome methylene blue or some other basic dye. The preparation shown in Fig. 55 is a portion of the mesentery preserved by being tied across the end of a short glass tube and immersed in alcohol. The tissue was then stained with methylene blue, and mounted without being sectioned. Most of it is colored pale blue, but the granules of the mast cells are deep purple. Such granules, which assume a color different from that of the stain employed, 'are called by Ehrlich metachromatic. The granules of mast cells are so coarse that in favorable places, when examined with an immersion lens, they can readily be counted. They spread over and obscure the nucleus, which appears as a pale central area.

Mast cells and eosinophiles were removed by Ehrlich from the miscellaneous group of plasma cells described by Waldeyer. Another type of cell was discovered in syphilitic connective tissue by Cajal, and independently described in tuberculous tissue by Unna (Monatsch. f. prakt. Dermatol., 1891, vol. 12, pp. 296-317). He states that these cells (to which the name plasma cells has come to be restricted) arise from normal connective tissue cells by the increase and rounding off of the cell body. As described by Unna, the granulation of the protoplasm is so fine that even with the highest magnification the individual granules cannot be distinctly recognized as such.

Typical plasma cells are shown in Fig. 56, p. They usually have very round nuclei with characteristic coarse masses of deeply staining chromatin. These masses may appear as wedge-shaped bodies with their broad ends against the nuclear membrane so that they resemble the spokes of a wheel ("Radkern"); or the chromatin blocks may suggest the squares of a checker-board. The nucleus occupies an eccentric position in the mass of dense and deeply staining protoplasm. Specific granulation, such as occurs in mast cells and eosinophiles, is absent. In certain plasma cells, vacuoles are seen (Fig. 56, v) which contain a "homogeneous, semifluid, colloid-like substance which has a strong affinity for acid dyes." If the affinity for such dyes has become well marked, these vacuoles form conspicuous structures, known as Russel's bodies. Usually they are regarded as degenerative products, but some investigators consider them as secretions.

Associated with plasma cells, lymphocytes are often found (Fig. 56, 1). These cells constitute an important class of white blood corpuscles or leucocytes. They differ from plasma cells in having only a small rim of pale protoplasm about the nucleus, but the nuclei of these two sorts of cells are very similar. Although Ehrlich (1904) agreed with Unna that only one source for the plasma cells had been established, "namely, an origin from hypertrophied connective tissue cells," many authorities now believe that they develop from lymphoid cells or lymphocytes. Councilman expresses this opinion as follows (Journ. Exp. Med., 1898, vol. 3, pp. 393-420):

As to their origin I hold the same opinion as Marschalko, that they are derived from lymphocytes. In the kidney they enter into the interstitial tissue by emigration from the blood vessels. They may emigrate from the vessels as plasma cells, or they may be formed from emigrated lymphoid cells. They have been seen in the act of emigration and the shapes of many of the cells in the interstitial tissue can leave no doubt as to their amoeboid character. We are led to the belief that the plasma cells have their origin in the lymphoid cells from the similarity of their nuclei to those of lymphoid cells and from the presence of transitional forms.

Downey (Folia haemat., 1911, vol. n, pp. 275-314) supplies a useful review of the literature of plasma cells, and expresses his opinion that they arise from several sources.

Plasma cells are found in connection with chronic inflammation of many sorts. They occur normally in abundance in the mucous membrane of the digestive tube from the stomach to the rectum, and they may be seen in bone marrow and in the lymphoid organs. Occasional plasma cells may be expected in subcutaneous tissue and in the breast.

Reviewing the preceding paragraphs it is seen that connective tissue contains nbroblasts_or connective tissue cells, and that mast cells, eosinophilic cells, plasma cells and lymphocytes may be lodged in the intercellular spaces. Except the plasma cells, which probably develop from lymphocytes, these are all comparable with forms of blood corpuscles normally found within the vessels. The source of these corpuscles will be further considered with the blood, together with other forms which sometimes leave the vessels but which are never regarded as constituents of connective tissue.

In the connective tissue of amphibia and mammals, Ranvier described certain slender branched cells which he named clasmatocytes (Arch. d'Anat. micr., 1900, vol. 3, pp. 122-139). This term refers to the detachment of portions of their processes, which Ranvier believed took place normally as a method of discharging a secretion. The breaking down was observed chiefly in amphibian cells which are now considered to be mast cells. Like other mast cells they are prone to distintegrate. The cells in mammals, to which Ranvier referred, are regarded by Maximow as derived from wandering lymphocytes. He believes that these may send out several processes, or become spindle-shaped, thus producing "clasmatocytes," but since this name is inappropriate he calls them resting wandering-cells. He finds that they contain a limited number of vacuoles and coarse granules, but the granules are said to differ from those of mast cells (Arch. f. mikr. Anat., 1906, vol. 67, pp. 680-757). The significance of these cells is uncertain.

Connective tissue contains two additional types of cells, which are so distinct that they may be regarded as separate tissues. These are the pigment cells and the fat cells; the latter will be described as adipose tissue.

Pigment cells. The color of the various tissues is due to pigments, which may be involution, like the haemoglobin in red blood corpuscles and the lipochromes in fat; or they may occur as granules imbedded in the protoplasm. The granules, which are yellow, brown, or black, often retain their natural color in stained specimens. They are said to consist of "melanin," which represents an ill-defined group of substances, some of which are haemoglobin derivatives. In the lung, inhaled soot is taken into the protoplasm of certain cells which thus become pigmented with extraneous material. Pigment granules are widely distributed, and may be found in the liver, spleen, heart, brain, and other organs.

In certain situations, pigment is extensively developed in branched connective tissue cells such as are shown in Fig. 57, A. In man these are of limited occurrence, being found near the eye, and in the pia mater, especially under the medulla oblongata and upper portion of the spinal cord. Weidenreich considers that this represents the remains of a general pigmented sheath for the entire nervous system. In lower vertebrates branching pigment cells are often abundant in the subcutaneous tissue, and changes

FIG. 57. A, Two pigment cells from the deep, peripheral __1__ ,.,,-1, oc nrrnr in frr>a<s

part of the cornea of the rabbit. B, Pigmented m COlOr, SUCn aS OCCUr in irOgS, epithelium from the conjunctiva of the guinea-pig. j , 4.-L- r ^-f ^^OI'^T-, /-.

The pigment is chiefly in the basal layer. are due tO the extension OT

retraction of these processes.

Such pigmented connective tissue cells are called chromatophores or chromatocytes. But in the human skin the pigment granules are in the epidermis, chiefly in the basal layers. In the stratified epithelium of the conjunctiva of the eye, toward the cornea, numerous pigment granules are found in the basal layers, and scattered groups occur also in the outer layers, as shown in Fig. 57, B. Pigment in this situation occurs frequently in the Caucasian race, and regularly in the other human races. Simple epithelium may be densely pigmented, as in the external epithelium of the retina. Thus it is seen that pigment cells are by no means limited to connective tissue.

Adipose Tissue

If in a freshly killed animal a loop of intestine is drawn out of the abdominal cavity, the blood vessels ramifying in its mesentery will be seen to be imbedded in a band of fat, which branches when the vessels branch, and diminishes in width toward the intestine as the vessels become small. The close relation between the distribution of fat and the course of the vessels is notable also in sections. Fat cells occur in groups or lobules around the vessels, and are found, with few exceptions, wherever there is loose connective tissue. They may also occur singly, as in some parts of the denser connective tissue of the breast.

When examined fresh, each fat cell appears as a large round oil-drop, which is more or less compressed into a polyhedral shape by the surrounding cells. It is highly refractive, having a border which becomes alternately bright and dark on changing the focus. The liquid fat or oil which fills the cell, leaving only an imperceptible film of protoplasm around it, may escape by the rupture of the membrane, thus forming smaller drops. In the specimen shown in Fig. 52 the fat was seen coming out from the upper surface of one of the cells, and the droplets thus emerging ran together forming larger ones. As fat cells develop, a coalescence of small drops occurs in the protoplasm.

The earliest formation of adipose tissue is said to occur in human embryos of the fourth month. It may be studied advantageously in the subcutaneous tissue of embryos of the fifth month (Fig. 58). In such specimens there are areas of loose and very vascular mesenchyma, found at the level of the roots of the hairs, in which certain cells exhibit vacuoles. These cells are at first quite like the surrounding fibroblasts,


EMBRYO OF THE FIFTH MONTH X 520. n Nucleus; f.v., fat vacuole; p. r., protoplasmic rim.


being fusiform or stellate. Their protoplasm contains several small vacuoles, some of which unite to form one large drop, and the nucleus together with the greater part of the protoplasm, is pushed to one side (Fig. 58, n). Sections of such cells have the form of "signet rings." Frequently small vacuoles are seen in the accumulation of protoplasm beside the nucleus. With further development the fat droplet becomes so large that the protoplasmic rim appears as a mere line or membrane, just within which is the greatly flattened nucleus. During the formation of the fat cells, the branching processes become very short, but it is doubtful whether they are altogether lost.

For some years after birth fat cells containing several vacuoles are found in certain situations, as around the kidney (Fig. 59) and in the outer layer of the cesophagus. Usually these are regarded as immature forms.

Adipose tissue of the adult, when well preserved, presents cells of



rounded form as shown in Fig. 60; often, however, their thin walls are bent or collapsed. If the sections are thick, a network of a different pattern, representing another layer of cells, will come into view on changing the focus. The nuclei of the fat cells are pale oval bodies, with finely granular chromatin (Fig. 60, n), often containing one or two small vacuoles. The protoplasm around the nucleus forms such a thin layer that it is scarcely appreciable on surface view. Both nucleus and protoplasm are much darker when seen on edge, since a thicker layer of substance is thus presented. When sectioned in this position the nuclei within the cells must be carefully distinguished from those of the connective tissue just outside. Many of the fat cells will show no nuclei, since the entire cell is usually not included within the limits of one section.

In extreme emaciation, the fat cells become small and the protoplasmic rim thickens, so that the cells again assume the signet-ring form. A


X 400. Connective tissue is seen at the left of the figure and

(as at c. t.) between the fat cells; n, nucleus

of a fat cell.



b. v. f blood vessel; f. c., fat cell.

delicate reticulum appears between the shrunken, cells as shown in Fig. 61. Some of the fibers proceed directly from the fat cells, indicating that the processes have never wholly disappeared. Others come from the fibrofrlasts which from the first are scattered among the fat cells.

The great difference between the appearance of fresh fat cells and those seen in sections is due to the fact that fat is dissolved by the reagents ordinarily used in preserving the tissue. Thus the sections usually show empty vacuoles and no fat whatever. Occasionally, as a result of cooling, the fat has formed insoluble crystals in the shape of radiating needles, and these, or an amorphous precipitate which takes a bluish stain with haematoxylin, may be seen within the cells. Although fat is the commonest substance to be found within the vacuoles in human


tissues, it is not the only material which may have filled them, and therefore to demonstrate the presence of fat, special methods must be employed. Fresh tissue may be preserved in osmic acid, which blackens not only fat but some related substances; or frozen sections of tissue may be stained with Sudan III or Scharlach R, which color fat droplets red and demonstrate them even when minute. These stains may also be used after preservation of the tissue in formalin. It may be noted that Sudan III has been fed to animals, thus imparting a pink color to the living adipose tissue. If the animal is lactating, the fat globules in the milk also become pink.

Fat vacuoles occur in many sorts of cells which do not belong to adipose tissue, such as the cells of the liver, cartilage, and striated muscle. These cells are not called fat cells, even if their protoplasm contains many vacuoles, and they do not resemble the cells of adipose tissue.

Since fat cells occur in lobular masses in definite places, as under the skin, around the kidney, in the bone marrow, etc., and since they supply the body with nutriment, it has been proposed to regard them as constituting glandular organs. They receive fat from the adjacent vessels and store it, or quite possibly they absorb carbohydrates and convert them into fats. The formation of fat has been said to begin in or near the nucleus with the production of granules, but the part which the nucleus plays is uncertain. The small vacuoles often seen within it apparently arise after the cell is full of fat. Mast cells have often been found associated with fat cells and it has been supposed that they contained secretory granules which were concerned with fat production. Like an internal secretion, fat is taken from the cells into the vessels and distributed over the body.


Tendons consist essentially of very dense connective tissue. They are composed almost wholly of parallel white or collagenous fibrils, com



X 160. INTRA VITAM. (Huber.)

pactly bound together in bundles. The cementing matrix contains tendomucoid. Closely applied to the bundles are the tendon cells which produced them. In ordinary longitudinal sections of tendon, the protoplasm of the cells is indistinct or imperceptible, but the nuclei appear in rows as seen in Fig. 62. In special preparations, particularly in those of the

7 6


P .b

delicate tendons found in the tail of a rat or mouse (Fig. 63), it is seen that the cytoplasm of tendon cells forms a plate-like layer which is folded about the fiber bundles, tending to encircle them. Moreover the cells are provided with lamellar or wing-like projections, which extend out between adjacent fiber bundles. Apparently there are protoplasmic connections, end to end, between the cells, which thus form longitudinal rows or chains; and in cross sections of the tendon some of the wing-like projections anastomose as seen in Fig. 64. Thus, as in connective tissue, the original syncytial arrangement of the mesenchyma is partially, preserved.

The primary tendon bundles, which consist chiefly of white fibers and tendon cells, contain also a small amount of elastic tissue in the form of fine, wide-meshed networks. The elastic fibers are said to occur especially near the cells and their processes. The primary bundles are generally grouped in secondary bundles or fasciculi, which are bounded by partitions or septa of looser connective tissue (Fig. 65). Within the septa there are nerves and blood vessels, in relatively small number. Lymphatic vessels are said to be


p. b., Primary bundle bounded by a cytoplasmic sheath. sh., which extends from a tendon cell, t.c. p., process extending into a primary bundle. The entire figure is a portion of a secondary bundle.



Septum. Blood vessel. Fasciculus. Fibrous sheath.


confined to the sheath of connective tissue which surrounds the entire tendon, with which the septa are continuous (Fig. 65).

The fibrous sheath or vagina fibrosa, which surrounds the tendon,



may contain a cavity filled with fluid. It is then called a mucous sheath or vagina mucosa. The cavity arises as a cleft in the embryonic connective tissue and its walls are formed of mesenchymal epithelium. The cells have become flattened and the fibers felted together to bound the space. It contains a fluid like that of the joint cavities, being chiefly water and a mucoid substance which renders it viscid, together with protein material and salts. The function of the mucous sheath is to facilitate the movements of the tendon. By its formation the tendon is freed from the local connection with surrounding tissue, and the sheath generally occurs where such connection would especially interfere with motion. The mucous burs<z are similar structures in relation with muscles or bones. The joint cavities, to be described later, belong in the same class, having a similar origin and function.

Aponeuroses, fasciae and ligaments are connective tissue formations, resembling tendon in possessing a more or less regular arrangement of cells and fibers. Elastic elements may be abundant.





Cartilage is a mesenchymal derivative, the development of which it is difficult to follow, since at certain stages its nuclei are so crowded that they obscure the transformation of the intercellular substance. Two interpretations of its development are illustrated in Fig. 66, A and B. As represented in A, the mesenchymal cells multiply and come together so that the intercellular spaces are obliterated. Thus precartilage is formed, consisting of large closely adjacent cells, separated from one another by thin walls which stain red with eosin. This type of precartilage has been frequently described in the lower vertebrates. It becomes cartilage by the thickening and chemical transformation of its exoplasmic walls. They form an intercellular ground substance or matrix, which stains blue with haematoxylin. According to Professor Mall the same result is produced in another way, as shown in Fig. 66, B. The mesenchymal cells in becoming precartilage produce a fibrillated exoplasm. The nuclei with the surrounding endoplasm then become "extruded from the syncytium" and lie in the intercellular spaces.



A, Based upon Studnifika's studies of fish; B, upon Mall's study of mammals. Mes.. Mesenchyma; Pre. Cart. precartilage; Cart., cartilage.


At the same time the fibrillated exoplasm becomes transformed into the homogeneous matrix of the cartilage, which stains blue with haematoxylin. Whether or not the cells are extruded may be questioned, but the relation of the fibrous to the homogeneous matrix, which is shown in the figure, may readily be observed around the vertebrae in pig embryos.

After the cartilage has formed, the cells occupy cavities, or lacuna, in the matrix. It is probable that in the living condition the cartilage cells completely fill their lacunae, but in preserved specimens they are often irregularly shrunken. Usually the protoplasm of each cell is of a spongy vacuolated texture, which is in part due to fat droplets and in part to glycogen; in ordinary sections, both of these substances have disappeared, leaving empty spaces.

Glycogen is a carbohydrate which resembles starch and is therefore sometimes called "animal starch." It is soluble in water, and soon after death it becomes converted into glucose. For both of these reasons it disappears from ordinary sections. Fresh tissues, preserved in strong alcohol and stained with tincture of iodine, exhibit glycogen as brownish-red granules which may be aggregated in masses of considerable size. Glycogen is found not only in cartilage cells but also in striated muscle and in the cells of the liver. In the embryo it has a wider distribution. At certain stages of development, according to Gage, it occurs in the cells of the nervous system and is abundant in the epidermis, the digestive tube, and the ccelomic epithelium. Its production, like that of fat, varies with nutritive conditions, and it accumulates in well-nourished individuals.

The cartilage cells are said to be enclosed in capsules, which are often transparent and inconspicuous linings of the lacunas. Sometimes they appear as rather broad bands which are concentrically striated, indicating that they were deposited in successive layers. The layers of newly formed matrix, which bound the lacunae, usually stain very dark blue with haematoxylin. The deep color is probably due to chondromucoid. Peripherally the color blends with that of the older matrix, which takes a pale blue stain. Like the intercellular substance of connective tissue the matrix of cartilage may contain white and elastic fibers, but in its commonest form it appears homogeneous and hyaline. Chemically it is a mixture of collagen, chondromucoid, chondroitin sulphuric acid in combination, and albuminoid substances (albumoid). The old term "chondrin" really means little else than the matrix of cartilage, which on superficial examination is found to be a dense body. Within it, however, the cells produce new ground substance and push themselves apart from one another by interstitial growth. The cells in the interior of the cartilage are often much larger than those at the periphery, and the increase in the size of their lacunae is probably accomplished by the resorption of the adjacent matrix. The cells divide by mitosis, and after division two of them are found in a single capsule. They then move apart, and a partition, at first very slender, is formed between them. They may remain


grouped as a pair, forming a bisected elliptical figure, or they may divide again, producing either a row of cells or a cluster of three or four (Fig. 66). Since the cells change their positions with difficulty in the dense matrix, they are regularly found in very characteristic groups. It has been asserted that certain cartilage cells undergo mucoid degeneration and become lost in the matrix. In old cartilage dark spots, staining intensely with haematoxylin, are suggestive of such a process. Such cells must be carefully distinguished from tangential sections of the deeply staining pericapsular matrix.

Cartilage grows not only by the interstitial increase of the cells and matrix in its interior, but more especially by appositional growth, through


FIG. 67. THE THREE TYPES OF CARTILAGE: A, HYALINE; B, ELASTIC; C, FIBROUS. (Radasch). a, b, Outer and inner layers of perichondrium; c, young cartilage cells; d, older cartilage cells; e, f, capsule surrounded by deeply staining matrix; g, lacuna.

the formation of new cartilage over its external surface. Around every cartilage in the adult, there is a connective tissue envelope, the perichon-\ drium, containing undifferentiated cells which multiply and become transformed into cartilage cells (Fig. 67, A). These are added at the surface, undergoing in a thin layer such changes as are shown in Fig. 66. The young generations of cells are therefore at the periphery of the cartilage, and the oldest cells, or the groups which they have produced, are in the center. Between them an interesting series of cytomorphic changes may be observed. Since the perichondrium is the formative layer, a more or less perfect regeneration of cartilage may occur after surgical operations if the perichondrium is left in place, but not otherwise. The perichondrium contains vessels and nerves, none of which pene


trate the matrix of the cartilage. In some cases, however, vascular connective tissue occupies an excavation in its peripheral portion. Whatever nutriment the cells in the interior of the cartilage receive is obtained by diffusion through the matrix. It has been asserted that this diffusion takes place through a system of canals penetrating the matrix, and passing from one lacuna to another as in bone. But in mammalian cartilage the only canals which have been recorded are presumably the result of shrinkage, such as may be produced by treating the specimen with absolute alcohol or ether.

The three principal forms of cartilage hyaline, elastic, and fibrocartilage and the exceptional "vesicular supporting tissue" may be further described as follows:

Hyaline cartilage, the commonest type, is characterized by its clear, pale bluish or pearly translucent matrix, which is ordinarily free from fibrils. The nasal cartilages, most of the laryngeal cartilages, and the tracheal and bronchial rings are of this variety, together with the xiphoid and costal cartilages, and the articular cartilages which cover the joint surfaces of the bones. In embryos the greater portion of the skeleton is at first formed of hyaline cartilage. Although the matrix usually appears homogeneous, it may be resolved into bundles of parallel fibers by artificial digestion, and its behavior toward polarized light indicates an underlying fibrillar structure. Sometimes, as a degenerative process, a network of fibers may appear in the matrix, staining red with eosin, and resembling the elastic fibers shown in Fig. 68, 3. Such a condition has been observed in the trachea. In degenerating portions of the laryngeal and costal cartilages, fibers having a luster like asbestos (or the mineral amianthus) are sometimes seen; according to Prenant these "amianthoid fibers" are neither white nor elastic. In old age a deposit of calcareous granules often occurs in the matrix of hyaline cartilage, and in some of the laryngeal cartilages this change may begin by the twentieth year. With the increase and coalescence of the granules, the cartilage becomes calcified, and blood vessels may enter it; but it does not form true bone. As with other calcified structures, such as tendon, treatment with acids shows that the underlying tissue has retained its characteristic features, and remains quite different from bone.

Elastic cartilage contains, in its matrix, granules, fibers or networks of elastic substance (Figs. 67, B, and 68) ; consequently its color is yellowish. It is found in the external ear, the auditory (Eustachian) tube, the epiglottis, and in certain small cartilages of the larynx, namely the corniculate and cuneiform cartilages and the vocal processes of the arytsenoid cartilages. It develops from hyaline cartilage, which it closely resembles. Within its matrix, granules of elastic material are deposited, which later coalesce to form fibers. Some authorities have stated that they



arise from the cells, but according to Schafer "their formation apart from the cells can be easily verified in the arytsenoid cartilage of the calf." The elastic nature of fibers within the cartilage matrix can be demonstrated by special stains, such as resorcin-fuchsin; they stain like the elastic fibers of connective tissue.

1. 2. 3.


i, Portion of a section of the vocal process of an arytaenoid cartilage of a woman thirty years old; the elastic substance is in the form of granules. 2_and 3, Portions of sections of the epiglottis of a woman sixty years old; a fine network of elastic fibers in 2, a denser network in 3. z, Cartilage-cell, nucleus invisible; k, transparent capsule.

Fibro-cartilage cannot be regarded, like elastic cartilage, as a late modification of hyaline cartilage. In its early development, as seen in the intervertebral disc of an embryo, its matrix is primarily fibrous. It is composed of anastomosing bundles of fibers which blend with the hyaline matrix of the adjacent vertebral cartilage as shown in Fig. 66, B. Instead of becoming transformed into hyaline cartilage, however, it develops into a cartilaginous modification of dense connective tissue. It is found typically developed in the intervertebral and interpubic fibro-cartilages. According to Stohr it forms the articular cartilage lining the sterno-clavicular, acromio-clavicular, and mandibular joints, together with the joints of the costal cartilages, and it covers the head of the ulna. Usually it is said to form the rims deepening the sockets of the shoulder and hip joints, together with the interarticular discs of the mandibular, sterno-clavicular and knee joints but these, according to Stohr, consist of dense connective tissue without the characteristic cartilaginous matrix. A portion of their cells are round, however. Even when typically developed, fibro-cartilage consists chiefly of interwoven bundles of white fibers With haematoxylin and eosin this ground substance is diffusely stained, since the fibers, colored by the eosin, are imbedded in a chondro-mucoid



g, Fibrillar connective tissue; z, cartilagecell (nucleus invisible); k, capsule surrounded by calcareous granules. X 240.



matrix which stains with haematoxylin. The cells are not flattened as in connective tissue. They are lodged in well-rounded lacunae (Fig. 69), bounded by capsules and zones of blue-staining matrix; and they are frequently arranged in pairs or small groups such as occur in other forms of cartilage. Their protoplasm is extensively vacuolated and is sometimes shrunken.

"Vesicular supporting tissue" is a form of precartilage which consists of large vesicular cells in close contact, bound together by firm walls; it is a "cartilage without a matrix." In many invertebrates it is an important tissue, but in adult mammals it is of limited occurrence. In man such a tissue is said to be present on the inner surface of the tendon of insertion of the M. quadriceps femoris, and in the sesamoid cartilage in the tendon of the M. peronaeus longus. This form of cartilage resembles the notochordal tissue at a certain stage of development, and it is called "chord oid tissue" by Schaffer.


Although the notochord is of entodermal origin (cf. p. 38), it gives rise to a tissue which has often been called cartilage. Notochordal tissue

^ > A ^



The notochordal syncytium is seen in the center of a mucoid matrix. The vertebrae are toward the right

and left, beyond the limits of the figure.

differs, however, from any of the types thus far considered. The principal stages in its development in the pig have been described by Williams (Amer. Journ. Anat., 1908, vol. 8, pp. 251-284), whose account may be summarized as follows:


In an embryo measuring 5.5 mm. the notochord is a rod of cells surrounded by a thin notochordal sheath. A cross section contains about eight wedge-shaped cells. In an embryo measuring 9 mm. it is larger, and a cross section shows about fifteen cells at the periphery, and three or four at the center. In an embryo of 1 1 mm. the cells have lost all definite arrangement and are more or less vacuolated. The vacuoles increase in size and number, and are found to contain mucin or a gelatinous mucinlike substance. In an embryo measuring 17 mm. the cell walls, which up to this time have remained intact, are breaking down (or being absorbed) and the mucin escapes from the vacuoles. The cells are united by strands of cytoplasm and the notochordal tissue now resembles mesenchyma. The syncytial network continues to enlarge, both by growth, and by the formation of a greater number of vacuoles. In a much older embryo (250 mm.) the formerly continuous peripheral sheet of syncytial tissue is broken in many places by large masses of mucin. In the center of this accumulation, the slender syncytial network seems suspended (cf. Fig. 70). In the adult the syncytium has become divided into groups of vacuolated cells imbedded in a gelatinous matrix. Thus it acquires a resemblance to cartilage in several particulars, but it should be regarded as a distinct tissue.

The human notochord undergoes a development similar to that of the pig. After it has ceased to be an epithelioid rod of cells, its most characteristic condition is that shown in Fig. 70, which includes a portion of the nucleus pulposus from an embryo of the fifth month. The notochordal tissue forms a vacuolated syncytium suspended in the gelatinous matrix, which, at the periphery of the nucleus pulposus, is bounded by a structureless membrane. Very rarely the notochord is the source of tumors which are composed of tissue similar to that normally found within the nucleus pulposus.


Bone develops relatively late in embryonic life, after the muscles, nerves, vessels, and many of the organs have been formed. The skeleton at that time consists of hyaline cartilages, which are later replaced by the corresponding bones of the adult. According to Kolliker, Robert Nesbitt was the first to point out that the bones are not indurated or transmuted cartilages, but are new formations, produced around the cartilages which are later destroyed. Moreover, in his "Human Osteogeny Explained in Two Lectures" (London, 1736), Nesbitt showed that certain bones develop directly from connective tissue without having been preformed in cartilage. These are now called membrane bones in distinction from cartilage bones. The membrane bones are the bones of the face and the flat bones of the skull. They include the interparietal or upper part of the occipital, the squamous and tympanic parts of the temporal, the medial pterygoid plate of the sphenoid, the parietal, frontal, nasal, lachrymal, zygomatic (malar) and palate bones, together with the vomer, maxilla and almost the entire mandible. Nesbitt correctly

8 4


concluded that there is but one method of bone formation, whether or not it takes place in relation with cartilage, but he was unaware of the existence of cells, and believed that bones were produced from an ossifying juice derived from the blood.

Development of bone. Bone formation begins with the production of a layer or spicule of matrix which stains red with eosin. As to the origin of this matrix there is the same difference of opinion which obtains in regard to other intercellular products. It has been asserted that it proceeds from osteogenic fibers, which are modified white fibers of the connective tissue. Frequently a spicule of matrix is seen to fray out into the connective tissue, as shown in the lower part of Fig. 71. Between the osteogenic fibers, calcareous granules may then be deposited until

Osteoblasts. Calcifying connective tissue bundles. Bone matrix. Bone cells.


the fibers are lost in a homogeneous calcified matrix. According to this opinion the matrix is essentially an intercellular formation. Others consider that the matrix is produced by a transformation of the exoplasm of bone-forming cells, or osteoblasts.

Osteoblasts are derived from mesenchymal or young connective tissue cells through an increase in their protoplasm and a shortening of their processes. They are found in contact with the surface of spicules of bone, arranged in an epithelioid layer (Fig. 72). There is great variation in their shape. Often they are pyramidal, but they may rest upon the bone either by a broad base or a pointed extremity. Their round nuclei may be in the part of the protoplasm next to the bone, or away from it as far as possible. Active osteoblasts tend to be cuboidal or columnar, but as bone production ceases they may become quite flat. They form bone only along that surface which is applied to the matrix. As the strand of bone grows broader through their activity, it encloses here and there an osteoblast, which thus becomes a bone cell (Fig. 72). Apparently bone cells do not divide, and if they produce matrix, thus


becoming more widely separated from each other, it is only to a slight extent and in young bones; they are therefore quite inactive. Each bone cell occupies a space in the matrix, called as in cartilage, a lacuna, but unlike the lacunae of cartilage those in bone are connected by numerous delicate canals, the canaliculi. In ordinary specimens the canaliculi are visible only as they enter the lacunas, which are thus made to appear stellate. The matrix around the lacunae resists strong hydrochloric acid which destroys the ordinary matrix, and so may be isolated in the form of "bone corpuscles." The "corpuscles" correspond with the capsules of cartilage, which may be isolated in the same way. The bone cells nearly fill the lacunae and send out very slender processes into the canaliculi. These may anastomose with the processes of neighboring cells, as

Osteoblast becoming a bone cell. Bone cell. Osteoblast.







can be seen in the embryo, but it is doubtful if this condition is retained in the adult. The processes, moreover, are so fine that ordinarily they are invisible.

The spicules of bone, containing bone cells and beset with osteoblasts, increase in size and unite with one another, so as to form a spongy network enclosing areas of vascular connective tissue. These areas are not entirely surrounded by bone, but retain connections with the exterior, through which the vessels may enter and leave. It is evident that if the spicules continued to thicken, while new ones were added at the periphery, the bone would soon become quite solid and heavy. This is prevented by the destruction or resorption of certain spicules, which begins at a very early stage. It may be studied advantageously in the developing mandible of a pig embryo, 10 cm. in length. At this stage the teeth are growing rapidly, and around each tooth the spicules of bone are being destroyed so as to produce a larger socket; at the same time the jaw is increasing in thickness by the formation of new bone over its outer




surface. Toward the area of resorption the osteoblasts become flatter and less numerous, finally disappearing.

In sections of bone, the places where resorption is going on may be recognized by the presence of large multinucleate cells, which Kolliker in 1873 name d "bone destroyers" or ostoclasts (preferably spelled osteoclasts). They are shapeless masses of protoplasm without any limiting membrane, containing usually from one to twenty nuclei (Fig. 73). In the largest of them, Kolliker counted from fifty to sixty nuclei. He


Haversian canals in the process of formation.

Blood vessels.

Perichondrial bone.

Finished Haversian canal.

-- Empty lacunae.


Endochondrial borderline.


believed that they arose from osteoblasts through repeated nuclear division. Apparently they are not due to a fusion of cells; and they have nothing in common, except their large size, with the giant cells of the bone marrow, which will be described in connection with the blood. Osteoclasts are found along the surface of the bone, sometimes forming rounded elevations or caps at the extremities of spicules, and sometimes imbedded in shallow excavations known as Ho-wship's lacuna. There seems to be no satisfactory evidence that the osteoclasts are the active cause of bone destruction. On the contrary they appear to be degenerating cells, produced by those conditions which lead to the dissolution of bone.


The processes of bone formation and resorption just described take place both in membrane and in cartilage bones. As the membrane bones enlarge, the central portion, through resorption, becomes loose spongy bone (substantia spongiosa), which is enclosed on all sides by an outer layer of compact bone (substantia compacta). In the flat bones of the skull the compact substance forms the outer and inner " tables, " which have the spongy "diploe" between them. The cartilage bones likewise consist of spongy and compact portions.

Hyaline cartilage.

Primary marrow space.

Perichondrial bone.



Replacement of the skeletal cartilages. The changes within the skeletal cartilages during the formation of bone may be studied advantageously in longitudinal sections of any developing "long bone," or in transverse sections of the vertebrae from pig embryos measuring about 10 cm. The vertebiae exhibit several processes which will be cut lengthwise in transverse sections. Fig. 74 represents a longitudinal section of a phalanx



around which ossification has begun. On either side of the shaft of hyaline cartilage, the matrix of which stains blue with haematoxylin, there is a strip of bone, the matrix of which is stained red with eosin. These strips are sections of a band of bone which completely encircles the middle part of the cartilage. It has been formed by osteoblasts which developed in the perichondrium. The portion of the cartilage which is surrounded by bone has begun to degenerate. Its capsules have been




Endochondrial bone.

Perichondrial bone


Perichondrial bone.


resorbed, and the enlarged lacunae are beginning to coalesce. The matrix of the cartilage in this region takes a deeper stain, and calcareous granules are being deposited within it.

On the left of Fig. 74, a bud of perichondrial tissue is seen entering the shaft of the cartilage, and similar buds may invade it from other sides. Within the cartilage the ingrowing perichondrial tissue forms the primary marrow, which is a very vascular connective tissue. As it advances, the walls of the lacunae are resorbed, setting free the cartilage cells. Formerly it was thought that these cartilages cells became osteoblasts, but they are now considered to be dying cells, without further function.


8 9

Meanwhile the cartilage continues to grow, especially in length. This is brought about by successive transverse divisions of the cells of the shaft, so that they become arranged in more or less definite longitudinal rows (Fig. 75). The thin transverse walls of the lacunae in these rows are

Hyaline cartilage (cells in groups).

Hyaline'cartilage (cells enlarged).



Osteoblasts. Osteob'lasts. Blood Osteoclasts.

vessels. Marrow




dissolved more readily than the thicker longitudinal walls, and the deepblue ragged spicules of calcified matrix which are thus produced, are therefore generally elongated. Osteoblasts, derived from the primary marrow, arrange themselves on these spicules, and form bone in the same manner



as elsewhere. Thus the spicules of calcified matrix, staining blue, become encased in the matrix of bone which stains red (Figs. 75 and 76).

From what has been said, it is clear that bone is formed both around the cartilage (perichondrial bone) and within the cartilage (endochondrial bone). In long bones and flat bones, ossification is at first perichondrial and later endochondrial; in short bones it is endochondrial until the cartilage has been entirely replaced. Thus the part taken by endochondrial and perichondrial ossification varies greatly in different bones. As the bone grows, the older parts which have formed in relation with



Endochondrial Perichondrial bor

Haversian canal.

Calcified matrix between endochondrial and perichondrial bone.

Blood vessel.


Remains of calcined matrix of cartilage.


MONTH. X 80.

the cartilage are resorbed. In the shaft of the humerus from a human embryo of the fourth month (Fig. 77), only a thin and interrupted layer of calcified cartilage remains to mark the boundary between perichondrial and endochondrial bone, and in the adult all traces of this layer have disappeared. This is true of most bones, but in the auditory ossicles calcified cartilage is found throughout life.

The final stages in the replacement of the cartilages by bone take place long after birth, when the bones have increased greatly in diameter and length. The growth in diameter is accomplished by the deposition of new layers externally, and the enlargement of the marrow cavity.




through resorption, internally. This explains why a band of metal placed around the bone of a young animal is later found within the marrow. The internal resorption takes place in such a way that a meshwork of spicules and plates, denser toward the periphery, remains within the shaft, and the marrow occupies its interstices. To a limited extent new bone is formed in the interior of the shaft by osteoblasts in its lining membrane, called the endosteum. The deposition of new layers externally is produced by osteoblasts in the periosteum, which is a specialized connective tissue layer surrounding the bone. It replaces, and apparently is derived from, the perichondrium of the original cartilage. The extent to which new bone is formed, and its distribution, may be determined by feeding madder to growing animals. This dye, as has long been known, imparts a red color to the matrix of bone deposited while it forms a part of the diet. By this means Kolliker determined that the deposition of periosteal bone is not uniform. In a given bone, there will be unstained areas, where no new bone is being formed, or where an external resorption is taking place. In this way the bones acquire their characteristic modelling.

Growth in length occurs chiefly through the activity of the uncalcified cartilage. In a long bone, ossification first produces a

band of bone encircling the cartilage, and then a hollow shaft of bone with a rounded mass of cartilage at either end (Fig. 78, A, B). The cells in these masses continue to divide, prolonging the longitudinal rows of cells such as are seen in Fig. 75. As ossification takes place at one end of these rows, new cells are formed at the other, and thus the length of the shaft or diaphysis increases. Certain bones have been found to grow more at one end than at the other. After a time osteogenic tissue invades the cartilages at the extremities of the bone, extending into them from the marrow cavity of the shaft. It forms a small bone within each, and these are known as epiphyses (Fig. 78, D). Between the epiphysis and the diaphysis there remains a layer of cartilage, called the epiphyseal synchondrosis, which allows further growth in length. The cells which it produces are added chiefly to the shaft. The relation of the epiphyses to the growth of bone was demonstrated by early experiments, in which metal pegs were placed in the bones of young animals. Pegs in the shaft scarcely separate from one another during growth, but a peg in the epiphysis moves away from one in the diaphysis. The epiphyses are formed at

art. D


Cartilage is drawn in black, and bone is stippled. art., Articular cartilage; ep., epiphysis; diaph., diaphysis.


r various times after birth, or, in the tibia, shortly before birth; they unite I with the diaphyses usually between the eighteenth and twenty-second I years, when the bones have acquired their full length. At that time nothing is left of the original cartilage except the layer of articular cartilage which covers the joint surfaces. Details in regard to the time when ossification begins in the various bones, the number of centers involved (for many bones have more than the three which have here been described), and the time when these join the main bone, will be found in textbooks of anatomy, and, together with many references to important studies of bone development, in Bidder's " Osteobiologie " (Arch. f. mikr. Anat., 1906, vol. 68, pp. 137-213).

Structure of Bone in the Adult. The properties of adult bone are essentially those of its matrix, which consists of organic and inorganic constituents intimately blended, and perhaps chemically combined. Of the inorganic matter, over 80% is calcium phosphate, Ca 3 (PO^; the remainder includes chlorides, carbonates, fluorides and sulphates of calcium, sodium, potassium and magnesium. In order to cut sections of bone, this inorganic matter must be removed, and decalcification is usually accomplished by placing the specimen, after it has been preserved, in dilute nitric acid (3-5%) for several days or weeks. The matrix then has the consistency of cartilage. Its organic portion, which remains, is composed chiefly of collagen, together with osseo-mucoid. The collagen occurs in very fine white fibrils which are gathered in bundles, arranged in thin layers or lamella. Within these layers the fibers occur in parallel sets which tend to cross one another at right angles, thus producing a lattice work. These "decussating fibers" are seen only in special preparations in which a lamella has been peeled off, so that it can be examined in surface view. The calcareous matter is said to be deposited in the cement substance between the fibers, and not within them. Coarser uncalcified fibers are found in embryonic bone and in certain situations in adult bone for example, at the sutures and the places where tendons are inserted. They also extend into the bone from the periosteum (Fig. 79), constituting the "perforating fibers" (Sharpey's fibers). The perforating fibers of the bones of the skull are entirely collagenous. These bones in the adult, together with the entire skeleton at birth, contain no elastic fibers; but in other bones of the adult elastic fibers accompany the perforating fibers (Schulz, Anat. Hefte, Abt. i, 1896, vol. 6, pp. 117-153).

The periosteum consists of two layers. It has an outer layer of dense connective tissue, rich in blood vessels and containing also lymphatic vessels and nerves. It blends with the surrounding looser connective tissue and in places with fasciae and tendons. The inner layer has few vessels but contains an abundance of elastic fibers. They are chiefly parallel with the long axis of the bone, but in the periosteum of the bones


of the roof of the skull they form an interlacing network (Schulz). Perforating fibers, such as were described in the preceding paragraph, may arise from this layer; and others, both white and elastic, derived from tendons, may pass through it into the bone. In this way the tendons acquire a very firm insertion. The cells of the inner layer of the periosteum are spindle-shaped or flattened connective tissue cells, together with the more cuboidal osteoblasts which rest against the bone. In young bones these are so numerous as to form a third layer of the periosteum. In the adult they are few in number, but are capable of proliferation, and together with those in the endosteum. they are the source of new bone after injury. The periosteum, in bodies which have been kept a week at 15 C., is said to be capable of producing bone when transplanted to another body; and after operations in which a shaft of bone has been shelled out from its periosteum, a new shaft may be formed.

Beneath the periosteum, as seen in the cross section of the shaft of a long bone (Fig. 80) , there are layers or lamellae of bone which are parallel

Suture. Perforating fibers. Periosteal lamellae.

/ I

Blood vessel. Volkraann's canal. Haversian canal.

FIG. 79. SECTION ACROSS A SUTURE IN THE SKULL OF AN ADULT. Prepared by Bielschowsky's method. X 80.

with the surface. These are the "outer ground lamellae" or periosteal lamella. They are traversed by Sharpey's perforating fibers and by small blood vessels lodged in the so-called Volkmann's canals. The bone cells occupy lacunae, situated between the lamellae, and in Fig. 80 they are seen as small spots. In the lowest part of the figure, a portion of the marrow has been included. The marrow is surrounded by the endosteum, external to which are the "inner ground lamellae" or endosteal lamella. These are parallel with the inner surface of the bone.

Between the periosteal and the endosteal lamellae there is a dense mass of matrix unlike anything found in embryonic bone. Scattered through it, numerous blood vessels are seen in cross section. Each vessel is surrounded by concentric lamella which present a very charac



teristic figure. Such vessels are said to occupy Haversian canals (named for the English anatomist, Clopton Havers). Volkmann's canals contain vessels, but they are not surrounded by concentric lamellae. An Haversian canal often contains two vessels, an artery and a vein, together with a small amount of connective tissue and occasional fat cells; flattened osteoblasts may rest against the surrounding bone, and send processes into it. The concentric lamellae enclosing an Haversian canal constitute

Resorption line.

Volkmann's canals.



ifif^" Periosteal lamellae. xT..- Perforating fibers.

' :: :&*;- ^ ^

_~ Haversian lamellae.

Haversian canal.


- Interstitial lamellae.

. Endosteal lamellae.

U Marrow.


an Haversian system. Interstitial lamella, irregularly arranged, fill the intervals between the Haversian systems.

The way in which the compact bone of the adult is formed from the trabecular network of the embryo is indicated in the diagram, Fig. 81 (cf. also Fig. 73). After an area of vascular tissue has been surrounded by bone, the osteoblasts form lamellae, gradually closing in from all sides until only a slender canal remains. Successive stages are shown in Fig. 81, B. V., H. C 1 , and H. C 2 , respectively. The deposition of the concentric lamellae is not continuous. It, is interrupted by periods of





(In part, after Duval.)

f., Fibrous layer of periosteum; o., osteogenic layer of periosteum; os., osteoblast; b.c., bone cell; B. V., blood vessel; H. C 1 ., beginning Haversian canal; H. C 2 ., complete Haversian canal; i. 1., interstitial lamellae, c. 1., concentric lamellae; Sh., Sharpey's perforating fibers.

resorption, after which the deposition of bone is resumed. Resorption lines are frequently seen in the Haversian systems (Fig. 80).

Longitudinal sections of decalcified bone show the way in which the Haversian canals connect with one another (Fig. 82). The lamellae are not so strikingly subdivided into the groups seen in cross sections, since both the concentric lamellae and the ground lamellae are longitudinal layers. The lacunae of the Haversian systems, however, are flattened, parallel with the course of the Haversian canals, whereas those of the interstitial lamellae are more rounded or stellate. The Haversian lacunas have been described as shaped like melon seeds. Certain features of bone which can scarcely be seen in decalcified

specimens are rendered conspicuous in layers of dried bone, ground upon an emery wheel until thin enough to be translucent. The Haversian canals and lacunae with the canaliculi projecting from them, are then empty, except for air and particles of bone dust. The specimens are mounted in thick balsam, which spreads over the bone without filling the lacunae and canaliculi. When seen under the microscope these structures appear black (Fig. 83), the air within them being highly refractive. In such preparations the way in which the canaliculi pass from one lacuna to another, their connections


Fat .drops.


Fat drops are seen in the Haversian canals. At z Haversian canals open on the outer, and at xx on the inner surface of the bone.

9 6



with the Haversian canal, and their manner of branching may be readily observed. Although these canals are all present in the decalcified bone, they are usually inconspicuous and often invisible. It has been impossible to determine absolutely whether the bone-cells anastomose with one another through these canals, but it is considered probable that their processes do not extend very far into them.

Vessels and Nerves in Bone. The blood vessels of the marrow, bone and periosteum freely connect with one another. Small branches from

the arteries and veins of the periosteum enter the bone everywhere, through the Volkmann's and Haversian canals, and anastomose with the vessels in the marrow. The marrow receives its blood from the nutrient artery, which gives off branches on its way through the compact bone and forms a rich vascular network in the marrow. Of the larger veins which drain this network, one passes out beside the nutrient artery and others connect freely with the vessels in the compact bone. Lymphatic vessels are found only in the outer layer of the periosteum. Numerous medullated and non-medullated nerves are present in the periosteum, where some of them end in lamellar

corpuscles. Others enter the Haversian canals and marrow, chiefly to innervate the vessels. The nerves will be described in a later chapter.



Bones may be joined in two ways, either by a synarthrosis which allows little or no motion between them, or by a diarthrosis which permits them to move freely upon one another.

In a synarthrosis the mesenchymal tissue between the adjacent bones may form dense connective tissue, such as passes from one bone to another across the sutures of the skull (Fig. 79) ; or it may form cartilage, in which case the joint is known as a synchondrosis. The cartilage may be hyaline, as in the epiphyseal synchondroses, but often it is fibrous, as in the intervertebral synchondroses.



In a diarthrosis the connective tissue between the bones remains comparatively loose in texture, and a cleft forms within it, containing tissue fluid. This is the joint cavity (Fig. 84). It is bounded in part by flattened connective tissue cells, which spread out and form an imperfect epithelium (Fig. 85). This is not a continuous layer of cells, since in many places the fibrous tissue comes to the surface. The connective tissue layer blends with the perichondrium, which in turn passes into cartilage, and a portion of the cartilage, uncovered by perichondrium, helps to bound the joint cavity.


car., Cartilage; j. c., joint cavity; 8. f., stratum fibrosum; s. s.,

stratum synoviale.


SHOWN IN FIG. 84. b. v., Blood vessel; car., cartilage; j. c., joint cavity; mes. epi.

mesenchymal epithelium.

The articular cartilages are sometimes fibrous (as noted on p. 81) but usually they are hyaline. They vary in thickness from 0.2 mm. to 5 mm., being thinner at the periphery. The cells near the free surface are flattened. In the middle strata they are rounded and are often arranged in groups; in the deepest layers they tend to be in rows perpendicular to the surface. The matrix becomes calcified as the cartilage connects with the bone, and a line of demarcation separates the calcified from the uncalcified portion (Fig. 86). In the uncalcified cartilage, cells with processes extending into the adjacent matrix have been described, and the deeper layers of flattened cells may exhibit lobed nuclei.

The joint capsule consists of an outer layer of dense connective tissue, the stratum fibrosum; and an inner loose layer of which the mesenchymal epithelium is a part, the stratum synoviale (Fig. 84). The fibrous layer is specially thickened in various places to form the ligaments of the joint.


9 8


It may cover the end of the bone, coming between it and the joint cavity; thus the distal articular surface of the radius is covered with dense fibrous tissue. In other joints, as in the shoulder and hip, such tissue forms a rim, deepening the socket of the joint. These rims are called labra glenoidalia. Large folds or plates of dense fibrous tissue may project into the joint, covered by the synovial layer, thus forming the menisci of the knee joint, and the articular discs such as are interposed inthesternoclavicular and mandibular joints. Nerves and vessels are absent from the articular cartilages of the adult, and also from the labra and articular discs.





The epithelium has fallen from the apex of the left yillus, exposing the connective tissue.

The synovial layer consists of loose connective tissue, generally with abundant elastic elements. In many places it contains considerable quantities of fat. It has nerves which may terminate in lamellar corpuscles, numerous blood vessels, and lymphatic vessels which may extend close to the epithelium. The "epithelium" is a smooth glossy layer of connective tissue with parallel fibers and small round or stellate cells containing large nuclei. The cells are sometimes infrequent, as in places where there is unusual pressure. Elsewhere they may be spread in a single thin layer, or heaped together, making an epithelium of three or four strata. The synovial membrane may be thrown into coarse folds (plied) or into slender almost microscopic projections (villi}. The latter impart a velvety appearance to the membrane on which they occur.



On microscopic examination the synovial villi are seen to vary greatly in shape. They are covered by a simple or double layer of synovial epithelium, and usually, but not invariably, they contain vessels. The synovia (synovial fluid) consists chiefly of water (94%), the remainder including salts, albumin, mucoid substances, fat droplets and fragments of cells shed from the membrane.





A tooth consists of three parts, crown, neck, and root or roots. The crown is that portion which projects above the gums; the root is the part inserted into the alveolus or socket in the bone of the jaw; and the neck, which is covered by the gums, is the connecting portion between the root and crown. A tooth contains a dental cavity filled with pulp. The cavity is prolonged through the canal of the root to the apex of the root, where it opens to the exterior of the tooth at the Joramen apicis dentis. The foramen is shown, but is not labelled, in Fig. 88. The solid portion of the tooth consists of three calcified substances, the dentine or ivory (substantia eburnea], the enamel (substantia adamantina), and the centent (substantia ossea) . Of these the dentine is the most abundant. It forms a broad layer around the dental cavity and root canal, and is interrupted only at the foramen. Nowhere does the dentine reach the outer surface of the tooth. In the root it is covered by the cement layer, which increases in thickness from the neck toward the apex; and in the crown it is enclosed by the broad layer of enamel. The enamel, however, becomes thin toward the neck, where it meets and is sometimes overlapped by the cement. The pulp, dentine, and cement are of mesenchymal origin, the dentine and cement being varieties of bone. The enamel is an ectodermal formation, but so intimately associated with the others that it may be described with them.






The Development of the Teeth. The first indication of tooth development in human embryos is a thickening of the oral epithelium, which has been observed in specimens measuring 11-12 mm. At this stage the oral plate, which marks the boundary between ectoderm and entoderm, has wholly disappeared, but it is evident that the thickening takes place in ectodermal territory. The tongue is well developed, but the upper and lower lips are not as yet separated by depressions from the structures within the mouth. Soon after the thickening has appeared, it grows upward in the upper jaw, and downward in the lower jaw, into the adjacent mesenchyma, thus forming an epithelial plate which follows the circumference of either jaw. It undergoes the same sort of transformation in both the maxilla and mandible, and the following description of the conditions in the mandible is therefore applicable to both. As the plate descends into the mesenchyma, it divides into a labial lamina in front,

a b c d


X 20.

a, Labial lamina; b, dental lamina; c, Meckel's cartilage; d, tongue.

which brings about the separation of the lip from the gum, and a dental lamina behind, which is concerned with the production of the teeth (Fig. 89). At first the dental lamina is inclined decidedly inward or toward the tongue, as seen in the figure, but later it descends from the oral epithelium almost vertically. Taken as a whole it is a crescentic plate of cells following the line of the gums, along which the teeth will later appear.

The further development of the dental lamina is shown diagrammatically in Fig. 90, A-D, each drawing representing a part of the oral epithelium above and dental lamina below, freed from the surrounding mesenchyma. The labial side is toward the left and the lingual side toward the right. Almost as soon as the dental lamina has formed, it produces a series of inverted cup-shaped enlargements along its labial surface (Fig. 90, B), and these become the enamel organs. There is a separate enamel organ for each of the ten deciduous teeth in either jaw, and they are all present in embryos of two and one-half months (40 mm.). They not



only produce the enamel but extend over the roots, so that they are described as forming moulds for the teeth which develop within their concavities. The tissue enclosed by the enamel organ is a dense mesenchyma, constituting the dental papilla. It becomes the pulp of the tooth, and produces, at its periphery, the layer of dentine. As the tooth develops, the connection between its enamel organ and the dental lamina

Oral epithelium.

Enamel organs.

Dental groove

Dental lamina.


Enamel organs. Necks of enamel organs. ABC D

FIG. 90. DIAGRAMS SHOWING THE EARLY DEVELOPMENT OF THREE TEETH. (One of the teeth is shown in verticle section.)

becomes reduced to a flattened strand or neck of epithelial tissue, which subsequently disintegrates.

In order to produce enamel organs for the three permanent molars, which develop behind the temporary teeth on either side of the jaws, the dental lamina grows backward, free from the oral epithelium. This backward extension becomes thickened and then inpocketed by a papilla, thus forming the enamel organ for. the first permanent molar in embryos of 17 weeks (180 mm.) . It grows further back, and gives rise to the enamel organ for the second molar at about six months after birth, and for the third or late molar (wisdom tooth) at five years. In rare cases, several of which have been reported, there is a fourth molar behind the wisdom tooth, and it is assumed that in these cases the dental lamina continued its backward growth beyond the normal limits (Wilson, Journ. Anat. and Physiol., 1905, vol. 39, pp. 110-134).

The permanent front teeth develop from enamel organs on the labial side of the deep portion of the dental lamina (Fig. 91). Owing to the obliquity of the lamina the permanent teeth are on the lingual side of the deciduous teeth. The enamel organs for the incisors develop slightly in advance of those for the canines, but all of these are indicated in an embryo of 24 weeks (30 cm.) described by Rose. He found the enamel organs for the first premolars in an embryo of 29 weeks (36 cm.) and for the second




FIG. 91. TEETH FROM A HUMAN EMBRYO OF 30 CM. (Modified from R6se.)

E. and E. O., Enamel organs of a deciduous and of a permanent tooth respectively; D. R., dental lamina; O. E., oral epithelium; P., papilla.


premolars at 33 weeks (40 cm.). Each front tooth develops in the alveolus occupied by the corresponding deciduous tooth, but later a bony septum forms between the two teeth and subdivides the alveolus. When the deciduous teeth are shed, the partitions are resorbed, together with the dentine and cement of the roots of the deciduous teeth. This resorption is accompanied, as in bone, with the production of osteoclasts.

The portion of the dental lamina which is not utilized in producing enamel organs becomes perforated and forms irregular outgrowths (Fig. 91). This disintegration begins in the front of the mouth and spreads laterally. Epithelial remnants from the lamina have been found in the gums at birth and have been mistaken for glands. Like other epithelial remains they occasionally develop abnormally, forming cysts and other tumors. The deepest part of the lamina, below the enamel organs of the permanent teeth, is considered by Rose to be a possible source of a third set, and he states that a case has been reported to him in which such a set, consisting of thirty-two teeth, developed on the lingual side of the permanent teeth. The models which Rose prepared, showing the enamel organs in various stages of development, form the basis of present accounts of tooth development. They are described and well illustrated in the Arch. f. mikr. Anat., 1891, vol. 38, pp. 447-491.


The basal cells of the oral epithelium may be followed as a distinct layer over the dental lamina and enamel organ, as shown in Fig. 92. This suggests that the enamel organ should be regarded as an infolding of the oral epithelium, and the occurrence of a transient dental groove immediately above the lamina (Fig. 90, C) favors this interpretation. The basal surface of the epithelium of the enamel organ is therefore directed toward the surrounding mesenchyma, and the superficial cells are found in the interior of the organ. At first these internal cells are in close contact, like those of ordinary epithelium, but later, through an accumulation of gelatinous intercellular substance, they constitute a protoplasmic reticulum which resembles mesenchyma, and is known as the enamel pulp (Fig. 93). No vessels or nerves penetrate this pulp. On the side away from the dental papilla the enamel pulp is bounded by the outer enamel cells. At first these are typical cuboidal epithelial cells, but later they become flattened and transformed into a feltwork of pulp fibers. Toward the dental papilla the enamel pulp is bounded by inner enamel cells, which develop differently over the upper and lower parts of the tooth respectively. Over the lower portion of the dental papilla they remain as cuboidal or low columnar cells. Here, through a thinning of the pulp, they are brought into contact with the outer enamel cells, and



the two layers together form the epithelial sheath of the root (Fig. 102). Over the upper part of the dental papilla, the inner enamel cells elongate and become enamel-producing cells or ameloblasts (Fig. 93).

The ameloblasts produce enamel along their basal surfaces, which are toward the dental papilla, but they become so transformed that their basal surfaces appear like free surfaces, and the entire cells seem inverted. In columnar epithelial cells the nuclei are generally basal, and the secretion gathers near the free surface, but in the ameloblasts these conditions are reversed. The nuclei are toward the enamel pulp,


Thickened ' W!-^ff&$i&

oral ithelium. . '.

Outer'enamel cells

Enamel pulp Inner enamel cells

Free edge of the dental lamina .



and the latter forms a dense layer over the ameloblasts, suggesting a basement membrane (Fig. 93). According to Cohn (Verh. phys.-med. Ges. Wiirzburg, 1897, vol. 31, No. 4) both ends of the ameloblasts are encircled by terminal bars. These bars may be regarded as modifications of the thin film of cement substance found between the ameloblasts. Near the center of each cell, and therefore on the basal side of the nucleus, Cohn has described typical centrosomes or diplosomes.

Toward the dental papilla the protoplasm of the ameloblasts contains granules or droplets which blacken with osmic acid and presumably indicate secretory activity. The basal surface of each ameloblast presents



a cuticular border and gives rise to a tapering projection known as Tomes's process. Tomes's processes extend into the developing enamel, but they may readily be seen in specimens in which the layer of ameloblasts has shrunken away from the enamel, as in Fig. 93. Around these processes minute globules are deposited, which resemble the granules within the cells, since they blacken with osmic acid. They are described as composed of a horny substance similar to that found in the epidermis. This material may become fibrillar, and Tomes's processes also readily break up into fibrils. There is therefore an uncalcified fibrillar layer of

Cuticular Tomes's Enamel Dorder. processes, cement. Calcified, . . uncalcified dentine.

Enamel pulp. Outer enamel cells.

Odontoblasts. Pulp. Inner enamel cells


FIG. 93. PORTION OF A LONGITUDINAL SECTION OF AN INCISOR TOOTH FROM A NEWBORN KITTEN. X 300. In this section the Tomes's processes have shrunken away from the enamel cement.

Rectangle enclosing the portion of the tooth shown highly magnified in the adjoining part of the figure.

enamel next to the ameloblasts. Further from the ameloblasts the enamel is calcified and consists of rods known as enamel prisms (sometimes called enamel fibers) which are bound together by calcified matrix or enamel cement. The way in which the prisms develop has not been fully determined. They have been regarded as the calcified ends of the ameloblasts and also as intercellular deposits.

The formation of enamel begins at the top of the crown of each tooth and spreads downward over its sides. If the tooth has several cusps, a cap of enamel forms over each, and these caps later coalesce. The enamel increases in thickness by the elongation of the prisms, which extend across it from the inner to the outer surface.


When the tooth comes out through the gum, or erupts, the enamel is covered with a "persistent capsular investment" described by Nasmyth (1849) an d called "Nasmyth's membrane" (cuticula dentis). Huxley studied this structure as it covers the teeth in an embryo of the seventh month (Trans. Micr. Soc. London, 1853, v l- I > PP- I 49~ I ^4)- He found that the inner enamel cells could be easily removed, leaving the surface of the enamel covered with a finely wrinkled or reticulated structureless membrane. Upon adding strong acetic acid the membrane became voluminous and transparent, and was thrown into coarse folds. The ends of the enamel prisms could be seen through it. This dental cuticula is now generally considered to be composed of the last-formed uncalcified ends of the enamel prisms, which are composed of horny material. After the eruption of the tooth it is gradually worn away, remaining longest in the depressions of the enamel.

The fully developed enamel is the hardest substance in the body. Several analyses have shown that it contains less than 5% of organic matter. No cells or protoplasmic structures are found within it, but it exhibits various markings, shown in Fig. 94. The outer surface of the enamel of the permanent teeth, especially on the sides of the crown and on young teeth, presents a succession of circular ridges and depressions, which may be seen with a hand lens. These were discovered by Leeuwenhoek (1687), whose figure of them is reproduced in Fig. 94, A. He considered that they marked the intervals during the eruption of the tooth, and wrote, "For example, let us assume that the tooth has fifty circles or ridges; if this is so, the tooth has been pushed through the gum during fifty successive days or months." This explanation is not supported by any evidence.

The enamel, as seen in ground sections passing lengthwise through the tooth, shows numerous brownish bands which are broadest and most distinct toward the free surface (Fig. 94, B). These are the contour lines or lines of Retzius, first described in Miiller's Archiv, 1837 (pp. 486-566). The coarsest of them may be seen with the naked eye, but upon magnification these are resolved into a number of finer lines, and many new lines appear. Their direction is shown in the figure; they arch over the apex of the crown, and on its sides tend to be parallel with the long axis of the tooth. Thus they cross the enamel prisms, and are not the lines along which the enamel most readily fractures. Apparently they indicate the shape of the entire enamel at successive stages in its development, and for this reason they are called contour lines. When Leeuwenhoek's ridges are present, the lines of Retzius end in the furrows between them. It was once supposed that their brown color was due to pigment, and it is well known that the enamel of certain teeth in rodents is deeply pigmented and brown. But when the lines are highly magnified, no pigment granules



are found. It then appears that the lines are due to imperfect calcification of the enamel cement, which is often vacuolated where a line crosses it.

Another set of lines crosses the enamel radially, taking the shortest course from the dentine to the free surface. These radial lines are due to the arrangement of the enamel prisms, and fractures of the enamel tend to follow them. As seen in reflected light, under low magnification, they appear as alternating light and dark bands, often called Schreger's lines. The prisms in crossing the enamel are bent in such a way that they are cut in alternating zones of cross and longitudinal sections, respectively (Fig. 94, C). These zones vary in shape and sometimes the prisms in cross section form an island surrounded by longitudinal sections. Since an entire prism cannot be isolated or included within the limits of a single section, the course which they take is difficult to determine. There is no



A, Leeuwenhoek's figure showing ridges encircling the enamel. B, Longitudinal ground section of a canine tooth; c, cement; c. 1., contour lines (lines of Retzius); d. c., dentinal canals; i. s., interglobular spaces. C, Longitudinal section of the enamel of an incisor tooth, the dentinal surface being toward the left. The enamel shows zones of transverse and longitudinal sections of enamel prisms. D, Fragment of enamel showing prisms in longitudinal view, slightly affected by hydrochloric acid. X 350 (Koelliker). E, Cross section of the decalcified enamel of a canine tooth from a child of three years. X 350 (Koelliker). F, Cross section of enamel prisms of a permanent molar from a child of about eight years. (Smreker.)

evidence that they branch, and the greater surface which they cover at the periphery of the enamel, as compared with the dentinal surface, has been explained by an increase in the diameter of the prisms as they pass outward. Such an enlargement is not well marked, however, and is partly offset by an outward thinning of the interprismatic cement. Apparently there is an increase in the number of ameloblasts as the tooth becomes larger, and there may be some late-formed enamel prisms which do not reach the dentinal surface. The plan according to which the prisms bend is discussed in Koelliker's Gewebelehre (6th ed.) but it has never been fully explained.

The individual enamel prisms, when seen lengthwise, exhibit transverse markings. These may be made out in ground sections, but they become more evident after the prisms have been treated with acid (Figs. 94, D and 99). They have been regarded as artificial products, but probably they indicate successive stages in the elongation of the prism. Fre


quently the prisms, when isolated, appear beaded, with transverse bands at the places of constriction.

When seen in cross section the prisms have highly refractive outlines, from 3-6 fi in diameter. They were formerly described as polygonal and primarily hexagonal (Fig. 94, E) but Smreker finds that they are crescentic, as shown in Fig. 94, F (Arch. f. mikr. Anat., 1905, vol. 66, pp. 312-331). The convex side of the crescent, along which the interprismatic cement is most abundant, is always toward the dentine. The hollow of the crescent receives an adjacent prism which appears to have been pressed into it. Isolated prisms of this sort are therefore hollowed out on one side, and it is possible that they connect with one another by flanges or bridges (von Ebner, Arch. f. mikr. Anat., 1905. vol. 67, pp. 18-81).


The dental papilla has already been described as a mass of dense mesenchyma, enclosed and probably moulded by the enamel organ. At the end of the fourth month, shortly before the formation of enamel has begun, the outermost cells of the papilla become elongated and arranged in an epithelioid layer. Since they produce the dentine, which is the principal part of the tooth, these cells are known as odontoblasts . At first they rest against the inner enamel cells. Later a thin layer of predentine extends like a membrane between the ameloblasts and odontoblasts; it is seen as a white line in Fig. 92. As the layer of predentine widens and becomes calcified, the odontoblasts remain on its inner surface, which is toward the pulp. Five of them are shown in Fig. 95, together with their branching processes, one of


which proceeds from the cuticular border of each FROM WHICH TOMES'S FIBERS


cell and occupies a canal in the dentine. These DENTINE, FROM A TOOTH OF A

NEWBORN CAT. (Prenant.)

dental or dentinal canals (canaliculi dentales) are

readily observed in adult teeth. Their existence, and the fact that they open into the pulp cavity, were recorded by Leeuwenhoek in 1687. "The presence of fibrils of soft tissue within the dentinal tubes" was established by Tomes in 1856 (Phil. Trans., pp. 515-522). He found that if a section of a fresh tooth is placed in dilute hydrochloric acid and then torn across the tubes, fibrils will be seen projecting from the broken edges; and that if the pulp is pulled away from the dentine, fibrils can be drawn out from the tubes. By the latter method the cells shown in Fig. 96 were obtained. The fibers within the dentinal canaliculi are called dentinal, dental or Tomes' s fibers.



Recently von Korff, with special methods, has demonstrated another sort of fibers which lie between the odontoblasts and pass from the pulp into the predentine (Fig. 97, A). The fibers are apparently collagenous

FIG. 96.

Six odontoblasts with dentinal (or Tomes's) fibers, f. p., pulp processes. From the pulp at birth. X 240.



IN PIG EMBRYOS. (After v. Korff.) d., Calcified dentine; e. c., inner enamel

cells; f., fibrous ground substance of

dentine; od., odontoblasts; p., mesen chymal cells.

and among them, immediately beneath the layer of enamel cells, calcareous granules begin to be deposited (Fig. 97, B). These granules become abundant, and fill the ground substance of the dentine. Von Korff concludes that it is not the odontoblasts but the fibrils | of the pulp which give rise to the dentine, and similarly' he finds that in bone the osteogenic fibers develop from the surrounding mesenchyma rather than from osteoblasts (Arch. f. mikr. Anat., 1907, vol. 69, pp. 515-543). Studnicka agrees with von Korff that "the odontoblasts are really gland cells, which are only secondarily concerned in the formation of dentine and do not produce ground substance; their processes (the Tomes's fibers) serve to convey certain nutrient material to the parts far removed from the inner surface, and thus nourish the dentine." (Anat. Anz., 1909, vol. 34, pp. 481-502.) Von Ebner, however, maintains that von Korff's fibers are produced by the odontoblasts as part of the process of dentine formation.

Other very fine collagenous fibrils in the dentmal matrix are arranged like the decussating fibers in the lamellae of bone. They cross one another as they run longitudinally in the successively deposited layers of dentine. These layers are sometimes marked out by distinct contour lines, the direction of which is shown in Fig. 98. They indicate the shape of the entire dentine at various stages in its development, and show that




the root of the tooth forms after the crown is essentially complete. The innermost layers are formed last. In addition to the contour lines, dentine seen in reflected light shows the radial Schreger's lines, which follow the course of the dentinal canals but are said to be due to the fibrillar structure of the matrix between them.

Dentine when fully developed is not so hard as enamel and contains a much larger amount of organic matter (approximately 25%). When the inorganic substances are removed from enamel, the remaining tissue scarcely holds together, but dentine and bone, when so treated, leave a gelatinous matrix which preserves the form of the original object. The dentinal canaliculi pass radially through the dentine, often following a somewhat S-shaped course as shown in Fig. 94, B. In addition to these primary curves, they may show spiral twists and secondary curves. As they cross the dentine, they divide dichotomously a few times and give off many slender lateral branches, some of which anastomose with those from adjacent canaliculi (Fig. 99). They finally become very slender

Enamel prisms.

Dentine. Enamel.


i, Dentinal canaliculi, some extending into the enamel; 2, globules of calcified dentine projecting into the interglobular spaces, 3.



MOLAR TOOTH. X 240. I, Dentinal canaliculi interrupted by a stratum with many small interglobular spaces, 2. 3, bone lacunas and canaliculi.

and generally end blindly, but some terminal loops have been described. Each canal is surrounded by a resistant uncalcified layer known as Neumann's sheath. This sheath may be isolated with acids, and thus it is comparable with the "corpuscles" of bone and the capsules of cartilage. It is difficult to determine whether the processes from the odontoblasts extend the whole length of the canaliculi, but they are believed to do so. Tomes observed that the peripheral portion of the dentine is more sensitive than the deeper part, and considered that the fine ramifications of the odontoblasts respond like nerve fibers to stimulation. Nerves have been traced to the odontoblast layer at the base of the dentine, but it is doubtful whether they extend into the dentinal canals as some have reported.


The contact between the dentine and enamel is usually quite smooth. Each enamel prism rests in a shallow socket on the dentinal surface, and in places the dentinal canals extend into basal clefts in the enamel cement. A short distance beneath the enamel the dentine exhibits a layer of spaces, which in ground sections are filled with air and appear black (Fig. 94, B, i.s.). They occur along the contour lines, and are due to imperfect calcification of the cement in that region of the matrix which was the first to form. Each space is bounded by spherules of calcified matrix which project into it from all sides, and the cavities are therefore known as inter globular spaces (Fig. 99). Toward the root of the tooth they are smaller and more numerous than in the crown. They are said to be particularly abundant in poorly developed teeth.

The pulp consists of a fine network of reticular tissue together with the peripheral layer of odontoblasts already described. The odontoblasts persist throughout life, and may continue to produce dentine so that the root canals may become nearly or quite obliterated. They are also active in repairing injuries. Some of the late-formed dentine contains blood vessels and resembles bone, so that it has been called osteo-dentine. The odontoblasts connect with one another and with the rest of the pulp by protoplasmic processes. The pulp tissue is free from elastic fibers and from bundles of white fibers. It is very vascular. The small arteries entering the apical foramina send capillaries close to the odontoblasts, but normally they do not enter the dentine. Lymphatic vessels, according to Schweitzer, are found by injection to begin as a tuft of branches in the pulp of the crown; they empty into one or a few very wide vessels passing through the root (Arch. f. mikr. Anat., 1907, vol. 69, pp. 807-908). The nerves of the pulp are the medullated dental branches of the alveolar nerves, which enter through the apical foramina, lose their sheaths and form a loose plexus beneath the odontoblasts, between which they terminate in free endings.


Each embryonic tooth, consisting of its enamel organ and papilla, is completely surrounded by mesenchyma, which extends from the oral epithelium to the bony trabeculae of the developing jaw (Fig. 101). This mesenchyma gives rise to the dental sacs enclosing the teeth; each sac consists of a dense outer layer and a loose inner layer of young connective tissue (Fig. 102). Toward the base of the dental papilla the tissue of the sac is separated from the dentine by the epithelial sheath, which is a part of the enamel organ. After the crown of the tooth is well developed, the epithelial sheath disintegrates or becomes penetrated by cells of the dental sac, which are then transformed into osteoblasts and deposit bone directly


upon the outer surface of the dentine. This bone is a part, of the tooth and is known as the substantia ossea or cement. It is thinnest at the neck of the tooth, and increases in thickness downward toward the apex of the root, over which it forms a considerable cap (Fig. 88). The deeper part of the root develops after the eruption of the crown.

The cement contains typical bone cells, enclosed in large lacunae which connect with one another through canaliculi (Fig. 100). The dentinal surface sometimes appears resorbed and the dental canaliculi then end abruptly; occasionally they appear to anastomose with those of the cement.

Cross section of the orbicularis oris muscle.

Labial gland.

Dental lamina.

Enamel organ.


FlG. 101. VERTICAL SECTION THROUGH THE LIP AND JAW OF A HUMAN EMBRYO OF Six AND A HALF MONTHS. X 9 The lamellae of the cement, which are seldom well marked, are concentrically placed around the root. In young teeth Haversian canals are absent, but in old teeth they occur in the outer layers near the apex of the root. Connective tissue fibers, comparable with Sharpey's fibers in bone, pass radially through the cement. They cross the dental sac and enter the bone of the alveolus, thus binding the tooth to its socket,

As the tooth enlarges and fills the socket, the dental sac becomes reduced to a thin layer consisting of the alveolar periosteum externally and the dental periosteum internally, with vascular connective tissue between. Frequently these are described as a single layer. It may contain fragments of the epithelial sheath. It has few elastic fibers, but is well supplied with



vessels and nerves which are branches of those about to enter the apical foramen. Around the neck of the tooth, dense connective tissue forms the circular ligament (Lig. circulare dentis).

The gum (gingiva) is the part of the lining of the mouth which surrounds the tooth. It is covered by the stratified oral epithelium, in which

Dental sac.

Outer layer. Inner layer.

Outer enamel cells.

Enamel pulp.

Inner enamel cells.


Epithelial sheath.



Dental papilla (future pulp)

Blood vessel. Bony trabecula of the lower jaw.

FIG. 102. LONGITUDINAL SECTION OF A DECIDUOUS TOOTH OF A NEWBORN Doc. X 42. The white spaces between the inner enamel cells and the enamel are artificial, and due to shrinkage.

intercellular bridges are well developed, and this epithelium rests on tall connective tissue elevations or papillae. There are no glands in the gums. When the tooth erupts it makes a hole through the epithelium, but the margins of the aperture become inverted. Thus the epithelium extends close to the tooth and turns down as a sheath surrounding the neck. At the level of the upper part of the cement it ends abruptly. The connective tissue of the gums blends below with the circular ligaments. It contains few elastic fibers, but is very vascular and is often infiltrated with lymphocytes. Its lymphatic vessels drain outward, along the margin of the cheek and gums, and inward, over the floor or roof of the mouth, as shown by Schweitzer.

Muscular Tissue

Contractility is a fundamental property of protoplasm. In muscle cells it attains its highest development. Muscle cells are elongated structures, known as muscle fibers, which contain numerous longitudinal fibrils within their protoplasm. By the shortening of these fibrillated cells, muscular action results. The muscle fibrils, or myofibrils, may be free from transverse markings, as in smooth muscle; or they may exhibit a succession of dark and light transverse bands, as in striated muscle. Smooth muscle fibers enter into the formation of the viscera, and their action, almost without exception, is involuntary. Striated muscle, in so far as it constitutes the entire system of skeletal muscles, is voluntary, or under the control of the will, but the striated fibers of the diaphragm and upper part of the oesophagus are apparently involuntary. The special form of striated muscle, known as cardiac muscle, which makes the bulk of the heart and extends some distance in the wall of the pulmonary veins, is involuntary. The three principal forms of muscle, smooth, skeletal, and cardiac, are mesodermal in origin. Within the basement membrane of the sweat glands there are elongated ectodermal cells which have been described as smooth muscle fibers, but their contractile nature is still questioned. It is well| established, however, that the muscles of the iris, which control the size of the pupil, are derived from ectodermal cells which bud off from those f orm-P ing the optic cup. Ectodermal muscles in man are limited to these examples.

Smooth Muscle

Smooth muscle fibers are derived from mesenchymal or young connective tissue cells. Usually they are produced in layers which surround some tubular organ, such as a blood vessel, duct, or a part of the^ digestive tube. The fibers in these layers are generally parallel, and are usually either circular or longitudinal in relation to the organ which they envelop. Occasionally they are oblique, or irregularly interwoven. Fibers which encircle an organ are called circular or transverse fibers; they may be cut across or split lengthwise according to the plane in which the organ is sectioned. The same is true of the longitudinal fibers, which run lengthwise of the organ.

The formation of smooth muscle may be studied advantageously in the oesophagus of pig embryos, and its development in this position has been carefully described by Miss McGill (Internat. Monatschr. f. Anat. u. Physiol., 1907, vol. 24, pp. 209-245) A part of a longitudinal section of the oesophagus of a 27-mm. pig is shown in Fig. 103. In such a section the developing longitudinal smooth muscle fibers or myoblasts are cut lengthwise (s.l.) ; and the circular fibers, which form a layer internal to the longitudinal fibers, are cut across (s.c.). The loose mesenchymal network, from which these fibers arise, is continuous with them above and below. A third thin layer of muscle fibers is forming at m.m., and at the top of the figure, the entodermal epithelium which lines the oesophagus has been included, together with the basement membrane beneath it.

In becoming smooth muscle cells, the mesenchymal cells change from a stellate to a spindle-shaped form and come closer together, but they do not lose their protoplasmic connections with one another. In the outer part of their protoplasm coarse border fibrils or myoglia fibrils are produced, which are similar to the fibroglia fibrils of connective tissue (p. 64). According to Meves, the fibroglia and myoglia are identical. The latter are at the periphery of the muscle cells and pass from one cell to another for long distances. These fibrils may be strikingly demonstrated in the oesophagus of a 24-mm. pig, stained with phospho-tungstic acid haematoxylin.

The coarse fibers shown by Miss McGill in both the circular and longitudinal muscle layers in Fig. 103 are "often found lying in part near the surface of the cell, resembling the border-fibrils of Heidenhain." She states that they are produced by a coalescence of granules within the protoplasm, forming at first spindle-shaped bodies which later join end to end, making varicose fibers. Subsequently they become smooth. They may split into fine fibrils, and usually they decrease in number as the embryo grows older. "In places they may be entirely absent in the adult tissue; rarely they are abundant."

In addition to the peripheral myoglia fibrils, the protoplasm of smooth muscle cells contains fine longitudinal fibrils, which have been described as the active agents in muscular contraction. Thus Miss McGill finds that in the contracted portions of the muscle fibers the myofibrillae show "a distinct increase in caliber." She states that the fine myofibrils do not arise until the pig embryo reaches a length of about 30 mm. They are apparently homogeneous from the beginning, and are distributed uniformly throughout the protoplasm. Some of them are shown in the muscle layer m.m. in Fig. 103. Ordinarily these fibrils are indistinguishable in the close-grained, deeply staining protoplasm which characterizes the muscle cells.

Along the sides of the muscle fibers there are at first protoplasmic processes which bind them together. Later these seem to be replaced by white fibers, like those of ordinary connective tissue. They form a network investing the muscle cells, as shown in Fig. 104. This intermuscular reticulum, produced directly from the muscle fibers, is unusually well shown in the walls of the blood vessels in the umbilical cord. To some extent, according to Miss McGill, it is produced from special mesenchymal cells within the muscle layer, which develop into connective tissue cells. In many layers of smooth muscle, however, connective tissue cells are difficult to demonstrate. Finally it should be noted that elastic fibers are found between the muscle cells. They vary greatly in number, being especially abundant in the walls of arteries.


X 700. (After McGill.) b. m., Basement membrane; epi., epithelium; mes., mesenchyma; m. m., muscularis mucosae; n., nerve cells; s. c., circular smooth muscle cut across; s. 1., longitudinal smooth muscle cut lengthwise.


c., Connective tissue network; n., p., f., nucleus, granular protoplasm, and fibrillar protoplasm of a muscle cell.

From what has been said, it is ev'dent that smooth muscle retains its original syncytial nature, and that to some extent it resembles connective tissue. It consists of elongated contractile cells which are joined together, especially toward their extremities, by myoglia fibrils, and which are bound together laterally by a white fibrous network containing interspersed elastic fibers. These features, which are essential for understanding the action of smooth muscle, are usually difficult to observe in the compact tissue of the adult.

Smooth muscle fibers in the adult are fusiform, cylindrical or slightly flattened cells, varying in length from about 0.02 mm. in some blood vessels to approximately 0.5 mm. in the pregnant uterus. In the intestine they are said to measure about 0.2 mm. Their diameter, through the widest part, is from 4-7 /*,. Owing to the length of these fibers and the fact that they are not perfectly straight, they are seldom wholly included in a single section. Moreover they are usually so closely packed that their outlines are hard to follow. They may be isolated, however, by treating fresh tissue with a 35% aqueous solution of potassium hydrate, or 20% nitric acid. The fibers when shaken apart appear as in Fig. 105. Owing to the readiness with which they may be disassociated, the existence of connections between them has sometimes been overlooked or underestimated; but it is evident that independent cells, by shortening cannot cause the contraction of a tube. Branching fibers have been isolated from the aorta, and are said to occur also in the ductus deferens and bladder.


The fibers when sectioned longitudinally (see Fig. 17 7, p. 186) somewhat resemble connective tissue, from which they may be distinguished by the staining and texture of their protoplasm and the position of their nuclei, which are within the fibers. With haematoxylin and eosin the muscle substance takes a deeper and more purple stain than the connective tissue fibers, and it is not so refractive. In doubtful cases Mallory's connective tissue stain may be used, which colors the muscle substance red and the white fibrous tissue blue.

The nuclei of smooth muscle fibers are elliptical or rod-like bodies, containing a characteristic chromatic reticulum and sometimes several nucleoli (Fig. 9, A, p. 10). When the muscle fiber contracts, the nucleus shortens and broadens, but according to measurements made by Miss McGill (Anat. Rec., 1909, vol. 3, pp. 633-635) there is no change in its volume. She finds, however, that the chromatin tends to collect at the poles of the contracted nucleus, and states that "the nucleus appears to take an active part in the process of contraction." Frequently spirally twisted or bent nuclei are found in layers of contracted muscle (Fig. 106) and they have been regarded as occupying contracted fibers. It is probable, however, that the spiral nuclei occur in relaxed fibers, which have been crumpled together by the contraction of adjacent fibers. Along one side of the nucleus the centrosome may be found, occupying a shallow indentation of the nuclear membrane.

At the poles of the nuclei there is often an accumulation of granular protoplasm (Fig. 104, p. 115) which is sometimes pigmented. The fibrils diverge to pass by the nucleus, and the granular protoplasm occupies the conical non-fibrillated space which is thus produced.

The surface of the smooth muscle fibers is covered by ^^^szi^^ a delicate membrane, which is sometimes thrown into transverse wrinkles by the contraction of the fiber. Possibly the fibrils terminate in it. They do not appear p to become more compact as they extend into the tapering ^FIBERS FROM ends of the fibers and presumably they do not all extend DOG?' RTERY F A the whole length of the cell.

In transverse sections the fibers present rounded or polygonal outlines (Fig. 107). They vary in size, since some are sectioned through the tapering extremity and others through the thick central part which contains the nucleus. In the figure the substance between the fibers appears solid, and it has sometimes been described as cement, or as a membrane rather than as a reticulum.

The relation of the myoglia, reticulum and muscle fibers to the process of contraction has never been adequately explained. In the intestine, with the normal accumulation of food, the diameter of the tube becomes four times as great as in the contracted state, and the muscle layer becomes reduced to somewhat less than one-fourth of its original thickness. The muscle cells appear to slip by one another and to

-T^T -\f <B f rm a l aver on ly a f ew fibers thick.

After a certain amount of distention the tube will expand no further, and


a, Connective tissue septum; b, section of a added F^SSUrC CaUSCS it tO TUptUrC.

iblr through the nucil e u u s? : ' sei *" f a

Presumably the elastic and white fibers aid in restoring the normal caliber.

With extreme contraction, however, the white and elastic fibers no longer aid the muscles, but become crumpled into coarse folds, as seen frequently in contracted arteries. As to the muscle fibers themselves, Meigs concludes that during contraction fluid passes from them into the intercellular spaces, so that the fibers shrink in size and become darker; he states that they decrease greatly in length but remain of about the same diameter, while the spaces between the fibers become larger (Amer. Journ. Physiol., 1908, vol. 22, pp. 477-499). According to Miss McGill, the deeply staining nodular thickenings of muscle fibers indicate a normal form of contraction in which the fiber does not contract as a whole, but a wave of contraction passes over it. In these contraction nodes the diameter of the fiber becomes increased (Amer. Journ. Anat., 1909, vol. 9, pp. 493-545). The enlargement of such muscular tubes as the vessels and intestine appears to be passive and due respectively to the pressure of the blood or food within. After extreme contraction the elastic tissue probably serves to dilate the tube to a certain size.

Smooth muscle is nourished by capillary blood vessels which tend to follow the course of the fibers, and it is innervated by slender branches of the sympathetic nervous system.

Skeletal Muscle

The skeletal muscles develop primarily from the mesodermic somites, which have been briefly described in a previous section (p. 39). The transformation of a portion of each of these blocks of tissue into layers and masses of skeletal muscle fibers has recently been reviewed by Williams, from whose work Fig. 108 has been taken (Amer. Journ. Anat, 1910, vol. n, pp. 55100). In Fig. 108, A, the core of the somite has fused with the ventral and medial walls of the mass, and the tissue thus formed is streaming over the aorta and toward the notochord. This tissue, the sclerotome, becomes mesenchyma and gives rise to smooth muscle and various other mesenchymal derivatives. In the part of the somite left in place, near the groove x, the striated muscle fibers begin to develop. The cells here elongate at right angles with the plane of the figure, and 'thus lengthwise of the embryo. In an older stage (Fig. 108, B) these myoblasts have multiplied and have begun to form a plate of muscle tissue, the myotome, which extends ventrally as shown in C and D. The dorso-lateral wall of the somite has meanwhile become a plate of tissue, the dermatome, which with the myotome associated with it, is often called the dermo-myotome. The dermatome according to Bardeen produces only striated muscle fibers; Williams finds that it forms only dermal connective tissue, and others consider that it gives rise both to muscle and connective tissue. The myotome is "entirely transformed into muscle fibers." The way in which the myotomes extend ventrally and break up into the ventrolateral trunk and neck musculature, and the longitudinal fusion and splitting of the dorsal part of the myotomes to produce the deep back muscles of the trunk and neck, have been described by Warren Lewis (Keibel and Mall, Human Embryology, 1910). The skeletal muscles of the limbs have usually been described as arising from cells which have migrated into the limbs from the ventral part of the myotomes. If this takes place the cells which migrate become indistinguishable from mesenchymal cells, but Bardeen and Warren Lewis consider that " the myo tomes play no part whatever in the origin of the musculature of the limbs." Moreover, Lewis states that " the idea that myotomes play a role in the origin of the muscles of the head must be abandoned." A radical difference in the source of smooth and striated fibers has therefore not been demonstrated, but the two forms of muscle develop very differently. The myoblasts which produce striated muscle are found in the midst of a mesenchymal or connective tissue network, thus differing from the myoblasts of smooth muscle. The latter unite with one another through protoplasmic or fibrous processes; the striated fibers are bound together by connective tissue sheaths. In producing striated fibers, the myoblasts become greatly elongated cylindrical structures, with rounded or blunt ends. Although according to Schafer they generally do not exceed 36mm. in length, they sometimes measure from 53-123 mm. (Stohr); their diameter is o.oi-o.i mm. During the growth of the myoblast, mi to tic nuclear division takes place repeatedly, producing multi-nucleate cells; and in the adult fibers, a further multiplication of nuclei through amitosis has been reported. Each developing myoblast thus acquires a row of centrally placed nuclei, imbedded in granular protoplasm. In the outer part of the myoblasts coarse myofibrils develop, which, as seen in cross section, form an encircling ring about the nuclei and axial core of protoplasm (Fig. 109). The entire myoblast is surrounded by a membrane, to the formation of which the adjacent mesenchyma contributes.


ao., Aorta; d, dermatome; m, myotome; m. t., medullary tube; n, notochord; s, sclerotome; z, angle at which the myotome develops.


mes., Mesenchymal cell; f., myofibril; n. nucleus of a myoblast; s., sarcolemma.


The group of cells shown in Fig. 109 corresponds with a portion of the myotome in Fig. 108, D. It is sectioned in the same plane, but represents a later stage. In the adult, such an area of tissue as shown in Fig. 109 becomes a group of fibers as in Fig. no. The myoblasts have greatly enlarged, and their protoplasm is filled with myofibrils which are often arranged in "fields," known as Cohnheim's areas. These fields are cross sections of longitudinal bundles of fibrils known as muscle columns, which Schafer later named sarcostyles (i.e., muscle columns). The term sarcostyle is, however, often loosely applied to the separate myofibrils. It has been supposed that the fibrils in a column arise by the longitudinal splitting of a primitive myofibril, but in sections it often appears that the areas or columns are due to shrinkage. As the fibrils multiply, the nuclei, each surrounded by a small amount of granular protoplasm, migrate to the periphery of the fiber and rest just beneath the connective tissue investment. Occasionally a nucleus is found which has not reached the surface. Toward the end of the muscle fiber, the nuclei are numerous, and may retain their central position. The growth of the fiber in length is supposed to occur at the extremities.

The central position of the nuclei in myoblasts in pig embryos was clearly described by Schwann, in the second part of his treatise which established the cellular structure of animals (1839). He believed, however, that the myoblasts were formed by the coalescence of primary round cells arranged in a row. The gradual and nearly complete transformation of the protoplasm into longitudinal fibrils was correctly observed. Schwann found that the secondary cells, or mature fibers, were completely enclosed in structureless membranes, which were clearly seen in shrunken fibers (Cf. Fig. in).

Every striated muscle fiber is completely invested by a membrane named the sarcolemma (o-ap, flesh; Xe/x/xa, husk or shell). This term was introduced by Bowman (Phil. Trans., 1840) who described the membrane as "a tubular sheath of the most exquisite delicacy, investing every fasciculus ( or fiber) from end to end, and isolating its fibrillae from all the surrounding structures." He confirms Schwann's statement that it is not a fibrous structure derived from the surrounding connective tissue, and he states that the nuclei of the muscle come to lie "at or near the surface but within the sarcolemma." He adds, however, that he has seen similar cells in the sarcolemma itself. Since Bowman's time there has been prolonged discussion as to the nature of this membrane. The outer portion, which may occasionally contain nuclei, appears to be of connective tissue origin, and is comparable with a basement membrane. The inner part, or true sarcolemma, is a structureless membrane closely applied to the surrounding connective tissue. It appears to be much more definite than any membrane which invests smooth muscle fibers, to which the term sarcolemma has been extended by Heidenhain and others. The sarcolemma of striated muscle, however, is not yet thoroughly understood. Although the muscle cells are generally said to be within it, Baldwin finds that they are outside of the sarcolemma, between it and the fibrous basement membrane (Fig. 112, A). Accordingly he agrees with Apathy in regarding the myofibrils as comparable with connective tissue fibers. The possibility that the myofibrils are intercellular will be discussed under cardiac muscle.



A., Sketch to show the relation between the cells and fibers

according to Baldwin, a., Fibrous membrane; b., nucleus

of a muscle cell in vertical section; c., sarcolemma; d.,

myonbrils artificially separated.

B., Part of a fiber from a straight muscle of the eye of a calf. X 1000. The nucleus is seen in surface view; the sarcoplasm contains chondrioconta.

The appearances of skeletal muscle which have caused it to be called striated are found only in longitudinal sections, including those which are obliquely longitudinal. It is then seen that the myofibrils, which run lengthwise, are composed of alternating light and dark portions, and that they are so arranged that the dark parts of one fibril are beside the dark parts of the adjacent fibrils. As a result of the close crowding of the fibrils, alternating light and dark transverse bands appear to pass from one side of the fiber to the other, and these are the striations. They are shown in Fig. 1 1 2, A and B (at the right of A, the fibrils are represented as artificially frayed apart).

Bowman (1840) stated that "a decisive characteristic of voluntary muscle consists in the existence of alternate light and dark lines, taking a direction across the fasciculi."

He added that Leeuwenhoek had described the striae repeatedly, believing in the earlier years of his inquiry that they were circular bands around the fibrils, but later regarding them as of spiral arrangement, comparable with an elastic coil of wire, and in some way capable of retraction. Bowman recognized that they were caused by the " coaptation of the markings of neighboring fibrillae." He found that the muscle fibers can readily be split into longitudinal fibrillae with transverse markings, but that "in other cases their natural

cleavage is into discs, and in all instances these discs exist quite as unequivocally as the fibrillae themselves." The discs are produced when the ends of a muscle fiber are pulled apart (Fig. 113). Bowman regarded each disc as a plate of agglutinated segments, receiving a single segment from every fibrilla which crossed it. These segments he named sarcous elements; they are united endwise to form the myofibrils and crosswise to form the discs. Usually the longitudinal cohesion is much greater than the lateral, and in the wing muscles of insects, according to Schafer, the fiber "never, under any circumstances, cleaves across into discs."

The finer structure of the fibrils is illustrated in the diagram, Fig. 114, which represents a part of seven myofibrils, including three dark bands and portions of four light bands. Under polarized light the dark bands are doubly refractive or anisotropic, and the light ones are singly refractive or isotropic. Following Rollett's suggestion, the striations are often designated by letters. The dark band is called Q (an abbreviation for Querscheibe, or transverse band) and the light band is called J (applied by Rollett to a subdivision of the isotropic layer) . The light band is bisected by the ground membrane, or Krause's membrane, which appears as a very slender dark line, Z (Zwischenscheibe, or intermediate disc) . The lines Z are believed to represent continuous membranes which divide the muscle fiber into compartments called muscle segments, or sarcomeres. At the sides of the fiber, Krause's membranes join the sarcolemma, which bulges between them when the fibers are contracted (Fig. 112, A). Between Z and Q, in the highly developed striated muscles of insects, a band N has been described (Nebenscheibe, or accessory band). The dark band Q becomes gradually lighter toward its central part (thus forming h or Qti), and in its central part it is sometimes seen to be crossed by Hensen's median membrane, M (Mittelscheibe). The latter is believed to be similar to Krause's membrane, but more delicate. Like the other bands it may appear dark or light according to the focus. In the muscle fibrils shown in Fig. 115, the bands Q, J, and Z may be readily identified; M appears as a rather broad white line which may include Qh.



The fibrils consist of alternating dark bands, Q, and light bands, J. J. is traversed by the ground membrane Z, and Q by the median membrane M. In the right of the three muscle segments shown in the Sgure, the bands, N, have been drawn.


Between the myofibrils and completely surrounding them is the sar coplasm, which is a fluid substance containing interstitial granules, fat droplets, and glycogen. It differs from the protoplasm of the muscle cells which is found about the nuclei, and which is cut off from the sarcoplasm, according to Baldwin, by the sarcolemma. The granules have been carefully studied by Bullard (Amer. Journ. Anat., 1912, vol. 14, pp. 1-46) who discusses their staining reactions and probable composition. The significance of the interstitial granules could not be determined. The fat droplets are regarded as reserved food material, and they vary in abundance according to the quantity of fat in the food. Schafer has found no evidence that the isolated sarcoplasm of insect muscles is contractile, but he readily observed the contractility of isolated myofibrils. Moreover the activity of certain muscles in living embryos begins soon after the fibrils are differentiated.

In the process of contraction, according to Schafer, the hyaline substance of the myofibril passes from the light segment / into the dark segment Q, so that each sarcomere becomes short and broad. He refers to the photograph of the lowest fibril in Fig. 115 as showing that the dark substance is porous (note the end of the fiber toward the right). The sarcolemma bulges between the successive Krause's membranes, which are brought closer together (Fig. 112, A), and the length of each sarcomere is greatly reduced. The dark band Q may become light through the accumulation of hyaline substance within it, and the shortened and condensed J may become quite dark, causing a reversal of the original color relations. The sarcoplasm is said to be forced from between the dilated myofibrils in Q, into /. Others consider that contraction is due to a passage of fluid from the sarcoplasm into the myofibrils, and that the beaded form which the myofibrils often present, results from an intake of fluid through the ultra-microscopic membranes which are supposed to surround them. The latter interpretation is defended by Meigs (Zeitschr. f . allg. Physiol., 1908, vol. 8, pp. 81-120), and vigorously attacked by Schafer (Quart. Journ. Exp. Physiol., 1910, vol. 3, pp. 63-74). The older theories of contraction and the numerous papers on the finer structure of striated muscle are admirably reviewed by Heidenhain (Anat. Hefte, Abth. 2, 1899, PPi-iu).

Adult muscle is composed of such fibers as have been described in the preceding paragraphs. They are arranged in compact bundles, shown in cross section in Fig. 116. Around all the larger muscles there is a connective tissue sheath, or external perimysium, which extends into the muscle in the form of septa, thus subdividing it into bundles or fasciculi. These septa constitute the internal perimysium, and the connective tissue extends from them around the individual muscle fibers, blending with the sarcolemma. In the connective tissue of the diaphragm, elastic fibers are abundant; but the muscles of the extremities are poor in elastic tissue, containing only fine, chiefly longitudinal fibers, found especially in the perimysium externum.

Cross sections of striated muscle fibers are readily recognized. They have rounded-polygonal outlines formed by the sarcolemma and fibrous membrane, within which are the myofibrils, often shrunken from the membrane. The fibrils stain intensely with eosin. They appear as coarse granules, but their rod-like form becomes evident as they are followed up and down by changing the focus. The shifting picture thus presented is quite characteristic. Some fibers stain more darkly than others, owing to the varying abundance of sarcoplasmic granules.


In many animals, as in the rabbit, two sorts of striated muscles may be recognized red muscle (e.g., the M. semitendinosus and M. soleus); and pale or white muscle (e.g., the M. adductor magnus). Correspondingly there are two sorts of fibers. First, there are dark fibers with abundant sarcoplasm, well defined longitudinal striation, and poorly developed transverse markings, having in general a small diameter; these occur in red muscles. Secondly, there are pale fibers, with less sarcoplasm and better defined transverse striations, having a greater diameter. These are the more highly differentiated fibers. Although in some animals these two sorts of fibers are found in separate muscles, in others, as in man, they are mingled in single muscles. In general the most constantly active muscles (cardiac, ocular, masticatory and respiratory) contain the most fibers with abundant sarcoplasm. The muscles having many fibers with scanty sarcoplasm contract more quickly but are exhausted sooner.

The size of the muscle fibers is subject to considerable variation. They are said to enlarge at a uniform rate throughout the body until birth, when their diameter is about twice as great as in embryos of four months. After birth the fibers of certain muscles become much coarser than those in others. Thus the gluteal muscles have large fibers (av. diam. 87.5/0 and the ocular muscles have small ones (av. diam. 17.5 /A), as determined by Halban (Anat. Hefte, Abth. i, 1894, vol. 3, pp. 267-308). He finds that the diameter of the adult fibers in general is about five times greater than at birth. As a result of exercise the diameter of muscle fibers in rats may show an average increase of 25% according to Morpurgo (Arch. f. path. Anat., 1897, vol. 150, pp. 522-554). He states that the enlargement of the muscle takes place without an increase in the number of its fibers, but merely through the thickening of existing elements. The fibers which grow most are those which originally were thinnest, and which act as a reserve material with great capacity for growth. The enlargement of fully formed fibers apparently takes place through an increase in the sarcoplasm, without multiplication or thickening of the fibrils. After injury striated muscle gives slight evidence of regeneration, but it has been thought that latent myoblasts may become active. A proliferation of nuclei toward the injured ends of the muscle fibers has been recorded, but repair is chiefly through the production of connective tissue.



Longitudinal sections of skeletal muscles may be easily recognized by the presence of unbranched striated fibers, bounded by well-defined membranes, associated with which are the flattened peripheral nuclei. The striations Q and / are visible under low magnification. In a few situations, striated muscle fibers branch (Fig. 117). Branching has been reported toward the place where the muscle fibers of the tongue are inserted into the mucous membrane, and where the facial muscles end in the subcutaneous tissue. The way in which the fibers connect with tendon has been studied with conflicting results. Schultze finds that at the end of the muscle fiber the myofibrils are no longer differentiated into light and dark bands, but pass directly into the tendon fibrils, with which they are continuous (Fig. 118). "Muscle fibrils and tendon fibrils are parts of a single structure." (Arch. f. mikr. Anat, 1912, vol. 79, pp. 307-331). But Baldwin finds that the ends of the muscle fibers are primarily conical and are covered with sarcolemma; and the tendon fibrils connect with the sarcolemma at the apices of the cones. The processes of sarcolemma are thus primarily "dovetailed" into the tendon. Secondarily .the cones may blend to form a thickened flat layer to which perichondrial or periosteal fibers are attached. In no case is the sarcolemma penetrated by muscle fibrils or tendon fibrils, and therefore there is no continuity between them (Morph. Jahr., 1912, vol. 45, pp. 249-266). Thus Baldwin defends the generally accepted opinion.

Muscles are abundantly supplied with vessels and nerves, which are imbedded in the perimysium. The lymphatic vessels end in the septa without extending among the individual muscle fibers; but the blood vessels, through capillary branches, continue further and run between adjacent fibers, thus forming a plexus with elongated rectangular meshes. The nerves are chiefly motor, and a branch ends in contact with every muscle fiber, to which it transmits the impulse for contraction. Muscles also contain sensory nerves, having "free endings" and probably terminating also around the muscle spindles. The spindles are slender bundles of poorly developed fibers, generally situated near the septa formed by the internal perimysium, as seen in Figs. 116 and 119. All the muscle spindles are formed during embryonic life, and their abundance and distribution in the various muscles in embryos have been studied by Gregor (Arch. f. Anat. u. Entw., 1904, pp. 112-194). They have not been found in all muscles, and in certain muscles they are regularly more numerous than in others. Thus they have been reported as absent from the muscles of the eye, face, pharynx, small muscles of the larynx, the Mm. ischiocavernosus and bulbocavernosus, and certain others, including a large part of the diaphragm. They are numerous in the distal muscles of the limbs, and in certain muscles of the neck. The finer structure of the nerve terminations, both motor and sensory, will be considered with the nervous system.


Cardiac Muscle

A portion of the mesenchymal syncytium from which cardiac muscle develops is shown in Fig. 1 20. Its nuclei are found in the axial part of the protoplasmic strands, at varying intervals from one another. Peripherally a few myofibrils have developed from the chondrioconta, or protoplasmic granules, and these fibrils extend for considerable distances through the syncytium regardless of cell areas. They multiply rapidly, and form a peripheral layer of fibrils surrounding the central nuclei and axial protoplasm. Thus as seen in cross section, the strands of cardiac syncytium

and the myoblasts of skeletal muscle resemble one another. The fibrils exhibit alternating dark and light bands which are arranged as in skeletal muscle, and ground membranes (Z) develop across the fibers, bisecting the light bands (/). Thej striations, however, are not as regular and as highly developed as in 1 skeletal muscle. At the periphery of the fibers there is a sarcolemma, which is thinner than that of skeletal muscle, and was formerly overlooked. In early stages the muscle fibers in many places rest close against the endothelium of blood vessels; later they are surrounded by more or less connective tissue.

In the adult the cardiac muscle fibers anastomose freely, thus retaining their original syncytial arrangement (Fig. 121). They do not, however, form an irregular network, but are arranged in layers, in which the fibers tend to be parallel. Thus they are cut longitudinally in Fig. 121 and transversely in Fig. 172 (p. 179). The nuclei retain their central position. They are elliptical bodies with a conical mass of protoplasm at either pole. This protoplasm, as in smooth muscle, occupies the interval left between the fibrils as they diverge to pass by the nucleus. It is granular, and frequently contains brown pigment.

According to Apathy (Biol. Centralbl., 1888, vol. 7) "the contractile substance is a product of the muscle cell and the muscle cell is represented by the nucleus and surrounding area of protoplasm." "The myofibrils of the contractile substance are the histogenetic homologues of connective tissue fibrils, however much they may differ from them chemically or functionally." Baldwin has recently advanced a similar interpretation. He finds that the sarcoplasm between the fibrils differs from the protoplasm around the nucleus. Moreover he states that the perinuclear protoplasm, in both skeletal and cardiac muscle, is separated by the sarcolemma from the myofibrils and sarcoplasm (Fig. 112, A). In regard to smooth muscle, however, Baldwin merely notes that it should be reviewed in the light of these facts. The existence of a membrane around the nu icleus and granular protoplasm at its peles

FIG. 120. CARDIAC MUSCLE FROM A DUCK EMBRYO OF THREE DAYS. (M. Heidenhain, from McMurrich's "Embryology.")

Nucleus. Sarcoplasm. Fibrils. Lateral branch.

I would place smooth muscle in the same category, and make the fibrils extracellular. With muscle, therefore, as with connective tissue, the distinction between intracellular and extracellular appears to be arbitrary and conventional. It is interesting to note that the extrusion of the nuclei from the precartilage matrix to its surface, as described by Mall, may be comparable with the passage of the nuclei from the center to the surface of skeletal muscle fibers. Baldwin's papers are found in the Zeitschr. f. allg. Physiol., 1912, vol. 14, pp. 130-160, and, as regards cardiac muscle, in the Anat. Anz., 1912, vol. 42, pp. 177-181.

A feature of cardiac muscle which is unlike anything observed in smooth or skeletal fibers is the presence of intercalated discs. These are transverse lines across the fibers, which were formerly interpreted as cell boundaries, and some authorities still regard them as such. In the guinea-pig Jordan and Steele find that they first appear during the week before birth. Thus they are late in development, and they are relatively less abundant and simpler in the young than in adults (Amer. Journ. Anat, 1912, Vol. 13, pp. 151-17.3). If the cardiac syncytium ultimately became resolved into cells, it would resemble certain other syncytia in this respect; and cardiac muscle can be broken up into cell-like blocks, apparently along these discs. However, the discs occur at variable distances from one another, and very frequently they mark off non-nucleated portions of the syncytium. As many as four of them may extend partly across a single nucleus, as shown by Jordan and Steele, indicating that they are peripheral modifications of the myofibrils, and cannot be regarded as cell walls. Heidenhain (Anat. Anz., 1901, vol. 20, pp. 33-78) pictures them as always connected on one


The transverse lines (x) are partly light (where the fiber has broken) and partly dark (intercalated iscds.)


side with a ground membrane Z (Fig. 122), and states that they are somewhat narrower than a sarcomere (i.e., the distance between two successive ground membranes) . He regards them as the places where new sarcomeres form, thus providing for the growth of the heart. Jordan and Steele, among others, consider that they are places where individual fibrils are contracted, and the fact that they are shorter than adjacent sarcomeres favors this interpretation. The discs may extend straight across the fiber, but frequently they are broken into "steps" as shown in the figure.

There are, therefore, three peculiarities of cardiac muscle through which it differs conspicuously from skeletal muscle, namely, its anastomosing fibers, central nuclei, and intercalated discs.

Nervous Tissue

General features. In nervous tissue the protoplasmic functions of irritability and conductivity attain their highest development. Irritability is that property which enables the cell to react to various stimuli, such as pressure or light; and through conductivity the effects of stimulation are transmitted to distant parts of the cell, or to adjacent cells. In all animals the cells of the outer or ectodermal layer are those most exposed to stimulation, and the ectoderm accordingly gives rise to the entire nervous system. In some animals all the ectodermal cells have been described as equally responsive to stimulation, and the name "sensory layer" has been applied to the ectoderm as a whole. Usually, however, the sensory cells become specialized in definite and limited areas of the ectoderm. M. Schultze (1862) showed that the sensory cells of the nose and eye are epithelial elements, the bases of which are prolonged into filaments which serve as nerves to convey sensation. He taught that the specific functions of the sense organs depend on their respective epithelial cells, which accordingly may be designated as olfactory, gustatory, auditory or visual cells.

Not only does the ectoderm produce sensory neuro-epithelial cells, the nucleated bodies of which remain in the epithelium, but it gives rise to more deeply placed nerve cells, which connect with the epithelial cells and place them in communication with the muscles. In simple forms of animals this connection is very direct, and the response of the muscle to epithelial stimulation is quite automatic. In the higher animals there are both direct and indirect paths from the sensory endings to the muscles, and muscular action may be inhibited or initiated by certain of the centrally placed nerve cells.

The centrally placed cells in vertebrates constitute the spinal cord and brain, which together form the central nervous system. The bundles of fibers which convey impulses to and from the central nervous system, together with the cells associated with them, constitute the peripheral nervous system.

In the olfactory epithelium of vertebrates there are neuro-epithelial cells which send fibers directly into the central nervous system, but in other cases the nucleated bodies of the sensory cells are not found in the epithelium. They occur in circumscribed masses or ganglia, from which fibers extend both into the central nervous system, and outward to various sensory structures, where they terminate in contact with cells which stimulate them. Thus the stimulus which gives rise to a tactile sensation is received by the terminal ramifications of a nerve fiber in the skin. The stimulus is conveyed along this fiber (Fig. 123, a), through the spinal ganglion (b), into the spinal cord, where it produces several branches (at c). One of these branches passes to a motor cell, d, to which, through contact, it transmits its stimulus. The motor cell sends a fiber outward (e) to terminate in contact with a striated muscle, which is thereby stimulated so that it contracts. This direct path from the sensory ending to the muscle, provides for reflex or unconscious action, such as is taken when the hand is suddenly withdrawn from a painful contact. In such a case a considerable group of muscles may contract together, since the sensory fiber sends branches up and down the cord (/"), and these in turn give off collateral branches which pass to motor cells at different levels.


The cell which conveys the tactile sensation from the skin to the spinal cord gives rise to branches which terminate in contact with other cells in the spinal cord, as shown in Fig. 123, g. From these cells processes cross to the opposite side of the cord and pass up to the brain (ti), where they connect with nerve cells through which the sensations become conscious. These brain cells presumably become permanently modified by the sensations which they receive, so that they store experiences. As a result of the sensation transmitted from the skin, certain cells in the brain may send stimuli downward to the motor cells of the cord, which then cause the muscles to act voluntarily. The descending fiber crosses to the opposite side during its descent, and occupies the position in the cord shown in Fig. 123, i. A branch is shown passing to the motor cell, d.

From this sketch of the constitution of the nervous system, it is seen that it consists essentially of cells, made up of cell bodies and of fibers; the fibers are prolongations of the cell bodies. The cells are sensory, or afferent, conveying impulses toward the central nervous system; and motor, or efferent, conveying impulses away from the central system. Within the cord these cells connect with others, forming ascending and descending tracts, or bundles of fibers passing toward the brain and away from it, respectively. Fibers which serve to connect different levels of the cord with one another are known as association fibers; those which connect the opposite sides are commissural fibers.

Certain features in the development of the nervous system in lower animals, of interest in connection with the mammalian nervous system, are shown diagrammatically in Fig. 124. In sponges, according to Parker, there is no nervous tissue of any sort, but beneath the thin epithelium he finds elongated contractile cells which "resemble primitive smooth muscle fibers" (Fig. 124, A). They have been regarded as modified epithelial cells. Parker finds that they are stimulated directly, as a result


Longitudinal muscle; b, motor fiber; d, sensory fiberj e, epithelium on the under surface of the body, containing neuro-epithelial cells.

of changes in the sea-water, so that they slowly contract and close the orifices around which they are situated. Since the sponges are lower than any animals which are known to have nerve cells, Parker concludes that muscular tissue arose independently of nervous tissue, and is the more primitive (Journ. Exp. Zool., 1910, vol. 8, pp. 1-41).

In the medusae, neuro-epithelial cells, nerve cells, and both smooth and striated muscle fibers are present. According to Oskar and Richard Hertwig, the muscle cells are derived from the deep part of the ectodermal epithelium, and from the first they are connected with nerve cells or neuro-epithelial cells (Fig. 124, B). In other words, in the medusas muscle and nerve develop in primary communication with one another (Das Nervensystem der Medusen, Leipzig, 1878).

In the earthworm (Fig. 124, C) neuro-epithelial cells in the ventral body wall send fibers to a cord of nervous tissue which constitutes a central nervous system. From cells in this cord, processes extend to the muscles, as shown in the diagram. Thus the neuro-epithelial cell does not stimulate the muscle directly; it conveys an impulse to the motor cell which in turn acts upon the muscle. In addition to the cells shown in the diagram the cord contains ramifying association and commissural cells. Thus stimulation at one point on the surface of the animal may cause coordinated muscular contractions in different parts of the body. As Retzius has pointed out, if the neuro-epithelial cells should withdraw into the interior of the animal, leaving their branching process in the epidermis, the conditions in vertebrates would be closely paralleled.

The development and structure of the central nervous system and the sense organs will be considered in a later chapter. The following account deals first with the development of the spinal nerves, the spinal sympathetic system, and the cerebral nerves; and secondly, with the adult structure of these parts, including the ganglia, nerve trunks, and nerve endings.

Development of the Spinal Nerves

The formation of the medullary groove (or neural groove) as a longitudinal trough in the ectoderm, and its conversion into the medullary tube by the coalescence of its dorsal edges, have been described in a previous section (p. 37). The anterior part of the tube expands to form the brain; the posterior part becomes the relatively slender spinal cord.


c. c. f Central cavity; d. r., dorsal root; d. ra., dorsal ramus; ep., ependymal layer; g. c., ganglion cells; g. 1., gray layer; m. g., medullary groove; m. t., medullary tube; o. b., oval bundle; s. g., sympathetic ganglion; sp. g., spinal ganglion; s. ra., sympathetic ramus; v. r., ventral root; v. ra., ventral ramus; w. 1., white layer.

At about the time when the medullary tube separates from the epidermal ectoderm, some cells become detached from the medial dorsal portion of the tube and pass down on either side of it, as shown in Fig. 125, C and D. These cells constitute the neural crest. They multiply by mitosis and accumulate in paired masses, corresponding in number with the segments of the body. Thus they form the spinal ganglia. A typical cell of a spinal ganglion is at first round, but later becomes bipolar by sending out two processes, one toward the periphery and the other toward the medullary tube. These processes grow out from opposite ends of the cell (Fig. 126). With further growth the nucleated cell body passes to one side of the prolongations, with which it remains connected by a slender stalk. Such T-shaped cells are characteristic of the spinal ganglia. The fibers which grow toward the medullary tube enter its outer part and then bifurcate, sending one branch toward the brain and the other down the cord. These longitudinal fibers form distinct oval bundles just within

Bipolarcells. T-cell.

Since these bundles receive accessions of fibers from every spinal ganglion, they enlarge as they approach the brain. The fibers of the oval bundle branch freely at their terminations, and along their course they give off collateral branches, which enter


The bipolar forms are from a chick the deep substance of the cord. 1 he periph eral fibers from the spinal ganglia grow out ward through the mesenchyma, and terminate in sense organs or sensory endings, which will be described presently. The fibers of the spinal ganglia are essentially sensory or afferent, conveying impulses from the periphery toward the cord, and up the cord toward the higher nervous centers.

The efferent or motor fibers arise chiefly from cells, the bodies of which remain within the central nervous system. Each of these nerve-forming cells, or neuroblasts, sends out one long process called a neuraxon (or axone). The neuraxons of the motor cells leave the spinal cord, near its ventral surface, in bundles which unite to form the ventral roots. The ventral roots correspond in number with the dorsal roots, which are the bundles of sensory fibers passing into the cord from each spinal ganglion. Peripherally the ventral root joins the bundle of fibers growing outward from the spinal ganglion, and the two together form a spinal nerve. Every spinal nerve consequently has a dorsal (sensory) root, and a ventral (motor) root. The fibers from the two roots travel in the same connective tissue sheath, but otherwise they remain entirely distinct.

The fundamental facts which have just been reviewed eluded anatomists for centuries. The nerves, extending from the brain and cord to all the important organs, were regarded as tubes, conveying a vital fluid necessary for organic activity; when this supply was cut off, the organs ceased to perform their functions. Thus if nerves to the skin were destroyed, the skin became insensible; or if those to muscles were cut, the muscles could not contract. The possible existence of sensory and motor nerves with different functions was debated and generally rejected, until Charles Bell proved conclusively that "nerves entirely different in function extend through the frame; those of sensation; those of voluntary motion; .... these nerves are sometimes separate, sometimes bound together; but they do not, in any case, interfere with or partake of each other's influence." This brilliant discovery was verified by physiological experiments to determine "whether the phenomena exhibited on injuring the separate roots of the spinal nerves corresponded with what was suggested by their anatomy." Bell found that such was the fact. (An Exposition of the Natural System of the Nerves of the Human Body, with a republication of papers delivered to the Royal Society, London, 1824.)

It was at first supposed that the nerves grew out from the cord and brain and acquired connections with their end-organs; but the apparent difficulty which the fibers would have in reaching them, and the fact that the connections must be established before the nervous system can be functional, have led to the idea that the nervous and muscular systems are connected at all stages of their development. In tadpoles, however, Harrison has shown that such connection is not an indispensable requisite for the normal development of the muscles, since they are formed in a normal manner after the medullary tube and neural crest have been removed from the entire posterior portion of the body. He finds further that nerves grow out into the adjacent tissues from transplanted portions of the medullary tube. Therefore he concludes that the nerves normally grow out to their end-organs and unite with them, but that this takes place very early in development, when the paths are quite direct. Subsequent growth of the body causes the muscles to shift about and become widely separated from the central nervous system, so that the nerves become greatly elongated and follow irregular courses (Amer. Journ. Anat., 1904, vol. 3, pp. 197-220; 1906, vol. 5, pp. 121-131).


A, Two views of the same nerve fiber taken twenty-five minutes apart, during which time the fiber has grown 2On', B, Two views of another fiber, at lower magnification, taken fifty minutes apart.

The participation of the mesoderm in the formation of nerve fibers has repeatedly been asserted, and some authorities now consider that the long fibers passing from the spinal cord to distant muscles are formed from chains of cells, either mesodermal or ectodermal. Certain of Harrison's experiments were designed to show whether the nerve fibers are formed by peripheral cells or grow out from the central nervous system. In tissue, cultures, made by placing fragments of the medullary tube of tadpoles in lymph, at a stage when the tube consists entirely of round cells, he observed the actual growth of the fibers. Examined after a day or two of cultivation, in a considerable number of cases, they were seen extending out into the lymph clot (Fig. 127). Harrison concludes that the nerve fibers begin as an outflow of hyaline protoplasm from the nerve cells. The protoplasm is actively amoeboid, and, as a result of this activity, it extends farther and farther from its cells of origin, retaining its pseudopodia at its distal end. Similarly enlarged "cones of growth," provided with spiny processes, have been observed in preserved tissue by Cajal; and His, from embryological studies, had long maintained that the nerve fibers grow out from neuroblasts in the central nervous system and spinal ganglia. Harrison concludes that his experiments "place the outgrowth theory of His upon the firmest possible basis" (Anat. Rec., 1908, vol. 2, pp. 385-410).

Dorsal and Ventral Rami. Every spinal nerve, near the junction of its ganglionic and motor roots, divides into a dorsal and a ventral branch or ramus (Fig. 125, E). Each ramus receives both sensory and motor fibers, and is therefore a mixed nerve. The dorsal rami are distributed to the muscles and skin of the back; their terminal cutaneous branches enter the skin along a line extending from the neck down the trunk of the body, as may readily be shown in dissections of the adult. In embryos of 10-12 mm. these rami are present as short branches, which can be followed to the muscular condensations derived from the myotomes, but apparently at that stage they do not enter the skin. The ventral rami are longer. Most of them anastomose with the ventral rami of adjacent nerves, thus giving rise to the cervical, brachial and lumbo-sacral plexuses. They are distributed to the muscles and skin of the ventral body wall.


nerve; St., stomach.

Development Of The Spinal Sympathetic System

In mammalian embryos measuring 10-12 mm., each of the thoracic spinal nerves exhibits a branch directed toward the aorta, and ending in a rounded mass of ganglion cells. This is the sympathetic or visceral ramus, terminating in a sympathetic ganglion (Fig. 125, E). It is generally believed that the cells in the sympathetic ganglia migrate outward from those in the spinal ganglia, but an origin from cells of the medullary tube which wander out along the ventral roots has also been asserted. Although the cells of the sympathetic ganglia were formerly considered to be mesodermal (even after it had been shown that those of the spinal ganglia were ectodermal), it is now generally admitted that the entire sympathetic system is ectodermal. However, in the cervical region the spinal nerves at first do not have sympathetic rami, and the sympathetic ganglia consequently appear isolated in the mesenchyma. Their cells may have migrated in detached groups. Instead of eight ganglia on either side of the neck, corresponding in number with the spinal nerves, there are but three, known as the superior, middle and inferior cervical ganglia, respectively, and of these the middle ganglion may be merged with the superior. They are elongated structures, especially the superior ganglion, and presumably represent a fusion of segmental ganglia.

Each sympathetic ganglion in the thorax of the adult is connected with its spinal nerve by two rami communicantes, known as the white and gray rami, respectively. The white rami consist chiefly of fibers passing outward from the spinal nerve, and they are probably a persistence of the sympathetic rami of the embryo. The gray rami contain fibers passing from the sympathetic ganglia back to the spinal nerves, and apparently arise later. They are found not only in the thorax and abdomen, but also in the neck where, as usually described, they place the superior cervical ganglion in connection with the first four cervical nerves, the middle cervical ganglion in connection with the fifth and sixth, and the inferior in connection with the sixth, seventh and eighth. The succession of sympathetic ganglia on either side of the body, extending from the neck to the pelvis, become connected with one another through bundles of longitudinal nerve fibers, and thus they form the ganglionated trunk of the sympathetic nerve (Fig. 128).

From the ganglia of the trunk, bundles of nerve fibers grow out ventrally to supply the blood vessels and viscera. It is characteristic of these branches that they unite with one another freely, forming net-like sympathetic plexuses, within which there are many scattered nerve cells. When the nerve cells in these ganglionated plexuses are particularly abundant, the structure is called a ganglion, though generally retaining a plexiform character.

The principal branches of the cervical sympathetic trunk are the superior, middle, and inferior cardiac nerves, which grow out from the corresponding cervical ganglia. They extend to the heart (Fig. 128) and form the cardiac plexus, associated with which is the cardiac ganglion, situated under the arch of the aorta. These nerves, which are joined by branches from the vagus, innervate the heart. The cervical sympathetic trunks also send out nerves which form plexuses around the aorta and the pulmonary, subclavian and carotid arteries together with their branches. These innervate the smooth muscles in the walls of the vessels. Some of the fibers accompany the thyreoid arteries into the thyreoid gland and others are distributed to the pharynx and larynx.

The upper thoracic ganglia supply nerves to the aortic plexus and pulmonary plexus, and the latter enters the lungs. Large bundles of fibers proceeding from the "fifth or sixth to the ninth or tenth " thoracic ganglia of the sympathetic trunk, unite to form the greater splanchnic nerves, one on either side of the body, and branches from the remaining thoracic ganglia .__._. _ , form the lesser splanchnic nerves. These

coe. g., cceliac ganglion; -i ,. ., ..i i ? i

myentenc plexus; sbm. pi., sub- splanciimc nerves pass into the abdominal cavity

mucous plexus. . . . .

and join one another, forming a large ganglionated plexus on the sides and front of the aorta (Fig. 128). The sympathetic trunks in the abdomen also send branches to join this plexus. The great plexiform ganglion found around the cceliac artery, as it leaves the aorta, is called the cceliac ganglion (or plexus). A similar plexus surrounds the superior mesenteric artery. From these plexuses, as shown in ^the diagram (Fig. 129), sympathetic nerves extend through the mesentery, and they form a microscopic ganglionated plexus surrounding the intestinal tube, lodged between the longitudinal and circular layers of smooth muscle. This is the myenteric plexus (plexus myentericus). It innervates the muscle and sends branches into the tissue beneath the mucous membrane, where they form another plexus (the plexus submucosus). In this way the sympathetic system supplies the intestine. It sends its fibers into other organs, following the arteries, thus forming the hepatic, splenic, suprarenal and renal plexuses. In the pelvis the sympathetic rami form the hypogastric plexus, with branches distributed to the rectum, bladder and urogenital organs, and finally it accompanies the arteries down the legs, innervating the muscles in the walls of the vessels.


In 1664, Willis published a remarkably clear account of the nerve "commonly called intercostal because it rests against the roots of the ribs." This nerve, which is the ganglionated trunk of the sympathetic system, had generally been supposed to descend from the cerebral nerves. Willis described its connections with these nerves and, through each intercostal space, with the spinal cord. He noted the cardiac branches, and stated that the great mesenteric plexus, placed in the midst of the others, like a sun, sent its nerve fibers like rays in all directions (hence it came to be called the "solar plexus"). Willis found that this nerve sent branches to all the abdominal organs below the stomach. He considered that its function was to place the heart and viscera in connection with the brain so that they should act in harmony (Anatome cerebri, Amstelodami, 1664). Because of their frequent communications with other nerves, Winslow (1732) called the ganglionated trunks the Nervi sympathetic? maximi.

Bichat (Anatomic Gen6rale, 1802, translated by Hayward 1822) subdivided the nervous system into two parts "essentially distinct from each other, the one having the brain and its dependencies for its principal center, and the other having the ganglions." The latter is "almost everywhere distributed to the organs of digestion, circulation, respiration, and secretion." "Each ganglion is a distinct center, independent of the others in its action, furnishing or receiving particular nerves as the brain furnishes or receives its own. . . . The continuous thread that is observed

from the neck to the pelvis is nothing but a series of communications These

communications are often interrupted, without any inconvenience in the organs to which the great sympathetic goes." That the sympathetic system acts independently of the central nervous system, at least to a great extent, is its most prominent physiological characteristic.

Thus the sympathetic system merits to some extent the terms organic, visceral, or vegetative system, which have been applied to it. Burdach (1819) stated that it might be called the "automatic system," and the term "autonomic system" has more recently been used, but Burdach preferred sympathetic system, which has been internationally adopted by anatomists.

Development of the Cerebral Nerves

The nerves which are connected with the brain, supplying the skin and muscles of the head together with certain viscera, are built upon the same plan as the spinal nerves, of which they may be regarded as a continuation. They consist of dorsal sensory roots, and ventral motor roots which, however, do not unite to form single nerves. Certain cerebral nerves are wholly sensory and others consist merely of a ventral root, and are therefore entirely motor. Still others have no ventral roots, but receive motor fibers through lateral roots. The fibers in the lateral roots are like motor fibers of the ventral roots in that they arise from cells within the central nervous system, but their processes emerge from the lateral wall of the brain instead of the ventral wall. They come out immediately below the entering sensory fibers of the dorsal roots.

Beginning at the anterior end of the brain and proceeding toward the spinal cord, the cerebral nerves occur in the following order: olfactory, optic, oculomotor, trochlear, trigeminal, abducent, facial, acoustic, glossopharyngeal, vagus, accessory and hypoglossal.


Olfactory (not shown). Optic (fibers in the stalk of the eye, the lens of which is marked L). Oculomotor (Oc.). Trochlear (Tr.). Trigeminal, semilunar ganglion (s.-l.); ophthalmic (oph.), maxillary (va..) and mandibular (md.) branches. Abducent (Ab.). Facial, geniculate ganglion (g.); large superficial petrosal (1. s. p.). chorda tympani (ch. ty.), and facial (fa.) branches. Acoustic (A.), supplying the otocyst (Ot.). Glossopharyngeal, superior (s.) and petrosal (p.) ganglia; tympanic (t.), lingual (1. r.) and pharyngeal (ph. r.) branches. Vagus, jugular (j.) and nodose (n.) ganglia; auricular (au.) and laryngeal branches, rec. being the recurrent nerve; the main stem proceeds to the abdomen. Accessory, internal ramus joining the vagus, and external ramus (ex.). Hypoglossal (Hy.). Froriep's rudimentary hypoglossal ganglion (F.) sometimes sends fibers to the hypoglossal nerve, c.i, c.2, c.3, cervical nerves.

It is desirable to use the names of these nerves rather than the numbers often applied to them. The names are descriptive, but the numbers are arbitrary and were very variously employed in the older anatomical works. Unlike the spinal nerves, the cerebral nerves are not a series of similar structures. Moreover the recent demonstration of the Nervus terminalis in mammals indicates that the numbering may need further revision.

In embryos measuring about 10 mm., the cerebral nerves are all present and show their primary branches. Except the olfactory nerve, they are included in Fig. 130, in which parts derived from dorsal roots are unshaded; those from lateral roots are black; and those from ventral roots are crosshatched. They may be briefly described as follows.

The olfactory nerve, on either side of the head, consists of about twenty separate bundles of processes from the neuro-epithelial cells in the nasal mucous membrane. These bundles of neuro-epithelial fibers pass directly into the olfactory bulbs, which are portions of the brain. The wmero-nasal nerve is a bundle much longer than the others, which arises from a tubular epithelial pocket in the mucous membrane of the nasal septum. This pocket is a rudimentary organ of considerable interest, known as the vomeronasal (or Jacobson's) organ. Associated with the vomero-nasal nerve, but said to be distinct from it, there is a small ganglionated nerve which sends its fibers into the brain caudal to the olfactory lobe. Distally it is "distributed chiefly to the vomeronasal organ." This is the Nervus terminalis, discovered in fishes by Pinkus in 1894, and recently found in human and pig embryos and in adult dogs and cats (Johnston, Journ. Comp. Neur., 1913, vol. 23, pp. 97-120; and McCotter, ibid., pp. 145-152).

The optic nerve is a round cord of fibers extending from ganglion cells in the retina to the brain. It is quite unlike any portion of a spinal nerve, and will be described in connection with the eye.

The oculomotor nerve has only a ventral root, and consequently it is entirely motor. It is distributed to four of the six muscles which move the eye-ball (namely, the inferior oblique and the superior, medial and inferior rectus muscles) and to the muscle which raises the upper eye-lid (M. levator palpebra superioris).

The trochlear nerve arises from cells in the ventral part of the medullary tube, but its fibers, instead of passing directly outward, grow to the dorsal surface of the tube and cross to the opposite side before they emerge. Although the trochlear nerve must be regarded as a ventral root, its fibers leave the brain more dorsally than those of any other nerve. They come out at the notch or isthmus between the mid-brain and the hind-brain, and all of them pass to the superior oblique muscle of the eye-ball. This muscle, which runs through a fibrous ring or pulley (trochlea) attached to the frontal bone, turns the eye outward and downward.

The trigeminal nerve consists of dorsal and lateral roots. Its sensory cells form the semilunar ganglion, which gives rise to three large nerves, the ophthalmic, maxillary and mandibular (hence the name trigeminal). In general terms, the ophthalmic is the sensory nerve of the forehead and largely of the scalp; the maxillary is the sensory nerve of the front of the face and the upper teeth; and the mandibular distributes sensory fibers to the front of the tongue, the lower teeth, and the skin over the lower jaw. Unlike the ophthalmic and maxillary nerves, the mandibular is a mixed nerve, receiving all the motor fibers of the trigeminal. These motor fibers are distributed chiefly to the muscles of mastication, through the masticator nerve.

The abducent nerve is wholly a ventral root, and its fibers all pass to the lateral rectus muscle, which abducts the eye-ball (i.e., turns it outward).

The facial nerve is largely a lateral root, and is the motor nerve of the facial muscles. It has, however, a dorsal root (the so-called Nervus intermedius) and a ganglion known as the ganglion geniculi, or geniculate ganglion, since it occurs at a bend in the nerve. The facial nerve has three fundamental branches, all of which contain both sensory and motor fibers; these are the large superficial petrosal nerve, the chorda tympani, and the facial nerve (the name of the entire nerve being applied to one of its parts).

The acoustic nerve, which is wholly associated with the internal ear, is entirely sensory. Its large ganglion becomes subdivided into the vestibular ganglion, with fibers to the semicircular ducts or "organ of equilibration," and the spiral ganglion, which sends fibers to the auditory cells of the cochlea.

The glosso-pharyngeal nerve is chiefly sensory, but it has a small lateral motor root. It has two ganglia, one above the other, the superior ganglion (ganglion superius) and the petrosal ganglion (ganglion petrosum), respectively. The principal branches are the sensory tympanic nerve, which supplies the mucous membrane of the middle ear; the sensory lingual branch, which passes to the back of the tongue and ends in contact with cells of the taste buds, being the nerve of taste; and the mixed pharyngeal branch which is distributed to the pharynx. It supplies the stylo-pharyngeal muscle.

The vagus nerve, which is sensory, is joined by the accessory nerve, which is motor, so that the vagus is regarded as a mixed nerve. It has two ganglia, the jugular ganglion (ganglion jugulare} above, and the nodose ganglion (ganglion nodosum) below. Its principal branches are the sensory auricular branch, which is distributed to the skin of the external ear; the mixed superior laryngeal nerve, distributed to certain laryngeal muscles and to the mucous membrane of the larynx down to the vocal folds; the recurrent nerve, which terminates as the superior laryngeal in the vocal muscles and mucous membrane of the lower part of the larynx; cardiac branches, which anastomose with the cardiac sympathetic plexus; and finally, from the main trunk of the nerve as it passes through the thorax into the abdomen, branches to the oesophagus, trachea, lungs, stomach, small intestine, liver, spleen and kidneys. Many of these branches anastomose with the sympathetic system. The wide range of this nerve is indicated by the term vagus.

The accessory nerve is wholly motor, and consists of lateral roots which arise from the hind-brain, and also from the spinal cord as far down as the sixth cervical ganglion. Beginning as a small bundle of fibers underneath the dorsal roots on the side of the spinal cord, it increases in size as it passes upward toward the brain, receiving accessions of fibers in its course. It arches toward the vagus and descends in contact with it, finally dividing into external and internal branches. The external ramus supplies the sterno-mastoid muscle and a part of the trapezius; the internal ramus joins the vagus.

The hypoglossal nerve is made up entirely of ventral roots, and is the motor nerve for the lingual muscles.

In the head the sympathetic system is intimately associated with the cerebral nerves, along the main branches of which the ganglion cells migrate. They accumulate in four ganglia, all of which are associated with the trigeminal nerve. These are the ciliary, spheno-palatine, otic and sub maxillary ganglia (Fig. 128).

The ciliary ganglion receives its cells from the ophthalmic nerve and in part from the oculomotor nerve, with both of which it remains permanently connected. The sympathetic plexus which ascends around the internal carotid artery also sends fibers to it. Branches from the ciliary ganglion are distributed to the front of the eye, especially to the ciliary muscles and the dilator of the iris.

The spheno-palatine ganglion derives most of its cells from the maxillary nerve, but it is in communication also with the large superficial petrosal nerve and the sympathetic plexus around the internal carotid artery. Some of its fibers reach the orbit, but most of them are distributed to the mucous membrane of the nose and palate.

The otic and submaxillary ganglia both receive cells from the mandibular nerve, and both are in connection with the sympathetic plexus around neighboring arteries. The otic ganglion receives fibers from a prolongation of the tympanic nerve, and it sends branches to the parotid gland. The submaxillary ganglion is joined by the chorda tympani and sends branches to the submaxillary and sublingual glands.

The lower ganglia of the glossopharyngeal and vagus nerves the petrosal and nodose ganglia differ from the other ganglia in the head by being temporarily connected with rudimentary ectodermal sense organs. Their contact with the ectoderm is transient, however, and their cells are considered to have come down from the superior and jugular ganglia, respectively. They are thus strikingly analogous to the ganglia of the sympathetic trunk, and it may be considered that instead of being connected with their nerves by rami, they have remained in the main stems. Moreover the vagus nerves produce myenteric and submucous plexuses in the oesophagus and stomach, which are quite like those of the sympathetic system in the intestine, but the fibers pass from the nodose ganglion to these plexuses without the interposition of a ganglion comparable with the cceliac ganglion. In addition to sympathetic fibers, the vagus contains many direct fibers, which probably come especially from the jugular ganglion. At present, however, both the upper and lower ganglia are described as similar in structure and as resembling the spinal ganglia. The opinion here advanced, that the nodose and petrosal ganglia are sympathetic, must therefore be regarded as tentative.

Structure of Nervous Tissue

Owing to the extent of the ramifying processes characteristic of nerve cells, it is rare that an entire cell, even a small one, is included within a single section. A motor cell, such as sends its fibers from the cord to distant muscles, has never been seen as a complete, isolated structure. From what is known of its several parts, however, a diagram of such a cell may be put together, as shown in Fig. 131. At the top of the figure is the nucleated cell body, which in different nerve cells varies in diameter from 4-150 /*. Frequently this nucleated portion is referred to as the nerve cell in distinction from the processes which grow out from it. The processes include the relatively short and irregularly ramifying dendrites, which convey impulses toward the cell body, and a single fiber, the neuraxon, chemically and physically different from the others, which conveys impulses away from the cell body. If the various processes radiate from the cell body in several directions, as in Fig. 131, the cell is described as multipolar; if the neuraxon is at one end of the cell and a single dendrite at the other, the cell is bipolar (Fig. 126); sometimes the nerve cell has only one process and is unipolar, as in the mature cells of the spinal ganglion which have a T-shaped process, and in other cells in which dendrites have not developed. The dendrites have the granular structure of the protoplasm from which they grow out, and were therefore originally

named "protoplasmic processes." The neuraxon, although receiving delicate fibrils from the protoplasm, as shown by special methods, seems quite distinct from the cell body. At its origin it often appears as a clear slender cone, free from granules, implanted directly upon the cell body, or upon the root of one of the larger dendrites. It tapers as it passes outward, and its fibrils come close together so that they appear to unite. Beyond the apex of the cone, which is a place where the neuraxon is easily broken, the fiber enlarges and its constituent neurofibrils spread apart so that they are more readily distinguishable. They are imbedded in a fluid interfibrillar substance. The neuraxon may send out collateral branches, which are usually at right angles with the main fiber.

As the neuraxon passes out from a motor cell it is at first free from any surrounding sheath (Fig. 131, a). In the outer layer of the spinal cord it becomes coated with a layer of the refractive fatty substance known as myelin. This is formed in the cord or medulla spinalis, and fibers which have this sheath are said to be medullated fibers (Fig. 131, b). The cells of the neuroglia network, through which the nerve passes while within the cord, may take part in forming the myelin, but they do not produce a membrane around each nerve, and they are not shown in the diagram. On leaving the cord, the neuraxon is still surrounded by the myelin sheath, but the latter is invested by a membrane called the neurolemma or sheath of Schwann (Fig. 131, c). At quite regular intervals along the course of the fiber, the myelin sheath is constricted or interrupted, forming the nodes of Ranmer. These are 0.08-1.00 mm. apart, being closer together in growing fibers, and in the distal part of adult fibers Midway between two nodes there is a nucleus, which may be found at any point in the circumference of the fiber, just within the neurolemma; it occupies a depression in the myelin. Toward its distal end the fiber usually branches, and the branches are given off at the nodes. The myelin then becomes thin, so that the fiber is surrounded merely by neurolemma (Fig. 131, d), and finally this ends. The naked axis cylinder then breaks up in its terminal arborization, forming the motor organs attached to striated muscle fibers. In comparison with the size of its cell body, the neuraxon shown in the diagram is too short; in extreme cases, as in the neuraxons extending from the spinal cord to muscles in the foot, it may be actually more than a meter long, or several thousand times the diameter of the cell body from which it comes.


The medullated nerve fibers were the first parts of the nerve to be studied microscopically, and were referred to as "cylinders;" the central fiber was called the axis cylinder. Remak (Obs. anat. et micr. de syst. nerv. structura, Berlin, 1838) was the first to describe non-medullated nerves, which are still known as "Remak's fibers," but their nervous nature was not readily admitted. Moreover. Remak recognized that nerve fibers proceed from cells. Deiters (Untersuchungen iiber Gehirn und Riickenmark, Braunschweig, 1865) supplemented these observations by showing that all "ganglion cells" (referring to nerve cells within the spinal cord and brain) are centers for two systems of true nerve fibers, (i) the generally broader and always single and undivided axis cylinder process; and (2) the protoplasmic processes with their extensive system of minute branches. He discussed whether the nerve cells anastomose with one another, and concluded that all such anastomoses which had been reported were due to deceptive appearances. Thus the nerve cells were believed to communicate by contact and not by continuity.

The confused mass of interwoven fibers which sections of nervous tissue ordinarily present, is, therefore, not a general syncytium from which sensory and motor fibers run out, but an orderly arrangement of branching cells. Striking proof of this was afforded in Golgi's description of the olfactory bulb (1875). In the plate which accompanied his publication, the cells in the different layers, and their various processes, were drawn in black with absolute assurance; similar figures of "Golgi preparations" are now seen in all treatises on the anatomy of the nervous system (Fig. 132). Golgi found that if fresh tissue is placed in a solution of potassium bichromate and osmic acid, and is later transferred to a solution of silver nitrate, a heavy black deposit occurs in certain nerve cells, extending throughout their minutest ramifications, whereas adjacent cells are wholly unaffected. The process must be carried out with great care, and even then it is capricious; but this method has afforded fundamental information in regard to the forms of individual nerve cells.

In order to emphasize that the nervous system is built up of separate cells, the term neurone has been widely used to designate a complete nerve cell, with all its branches. Fig. 131, therefore, represents a neurone, together with certain sheath cells.

Recently, however, there has been a tendency to regard such a neurone as a syncytium, and in the latest editions of his "Lehrbuch," Stohr adopts this interpretation. He states that in so far as the neurone includes peripheral nerve fibers, it is a biological or syncytial unit, but not a single cell. It is considered to be a "biological unit" since it is well known that the cell body of the nerve cell is the nutritive or controlling center for the entire fiber; and any part of the fiber which is cut off from the cell body undergoes degeneration. Stohr considers that Schwann (1839) had the correct conception when he regarded the nerve fiber as "a secondary cell, developed by the coalescence of primary cells."

Opposed to the syncytial interpretation of a peripheral fiber are the experiments of Harrison, some of which have already been cited. He has shown that in the tadpole the sheath cells, or neurolemma cells, which are believed by some to produce the segments of the fiber which they surround, all migrate from the brain along the dorsal root. If the dorsal part of the cord is removed from tadpoles, the ventral roots are deprived of their sheath cells, but the fibers of the ventral roots grow out to their terminations nevertheless. If the ventral part of the cord is cut from beneath the dorsal part, the dorsal roots develop and have with them the sheath cells which normally would enclose the fibers of the ventral root. These sheath cells do not produce nerve fibers. Therefore Harrison concludes that the peripheral fibers are not syncytial.


A, Cell of Deiter's type, having a neuraxon ending at a considerable distance from the cell body; B, cell of

Golgi's type having a neuraxon with many branches ending near the cell body.

Recently W. H. and M. R. Lewis have caused sympathetic fibers to grow from pieces of the intestine of chick embryos placed in various saline solutions. These fibers show amoeboid endings. They branch freely and anastomose, but like the nerve fibers from the central nervous system "they are outgrowths from nerve cells and are not formed from pre-existing protoplasmic networks" (Anat. Rec., 1912, vol. 6, pp. 7-31) Another form of syncytium would result if neurofibrils passed across the places of contact between the neurones. According to Apathy, who has studied the neurofibrils of invertebrates with special methods and faultless technique, the neurofibrils pass freely from cell to cell (Mitth. Zool. Station, Naples, 1897, vol. 12, pp. 495-748). It is possible that this takes place in the vertebrate nervous system also. Anastomoses have been found between ganglion cells in the retina by Dogiel, and slender nerve fibers appear to anastomose in tissue cultures; but the staining of individual cells by the Golgi method, and the way in which degeneration may be limited to cell territories, are regarded as strong evidence against the existence of a general syncytium.

Structure of Ganglia

Although a ganglion is characterized by the accumulation of the bodies of nerve cells, it is traversed by many fibers, as seen in the section of a spinal ganglion (Fig. 133). Under higher magnification the cell bodies appear as in Fig. 134. The nuclei are large vesicular structures, round or oval in outline, containing a characteristic prominent nucleolus. They are surrounded by abundant, darkly staining, finely granular protoplasm, which exhibits its fibrillar structure only with special methods. Frequently the protoplasm contains pigment granules. The "reticular apparatus" is said to be present always, and slender intracellular canals (trophospongium) have been described (Figs. 5 and 6, p. 4). Finemeshed reticular networks have been found covering the exterior of the nerve cells, and they have been ascribed both to the terminal ramification of nerve fibers and to branches of the supporting tissue. A ganglion cell is often surrounded by flat or stellate cells arranged in concentric layers so as to form a sheath. Within the sheath there is a homogeneous membrane or capsule, on the inner side of which are cells arranged in a single layer, corresponding to the cells within the neurolemma of peripheral nerves. Connective tissue, containing small blood vessels, passes between the ensheathed cells of the ganglion.


In the embryo the cells of the spinal ganglia are bipolar, but generally they become unipolar, with T-shaped processes, as already described. In the ganglia of the acoustic nerve, however, the bipolar form is said to be retained, and these cells are not surrounded by capsule or "mantle" cells. In other ganglia of the cerebral nerves, and in spinal ganglia, the cells are arranged as shown in the diagram, Fig. 135. Their branches can be studied only in special preparations, made usually by Ehrlich's methylene blue method, or CajaPs silver nitrate method.

Cross section of a medullated nerve fiber.

Longitudinal view of medullated nerve fibers. Surface view of nucleated sheath.


At x the beginning ofl a protoplasmic process has been included in the section; elsewhere the processes cannot be seen.

The most characteristic cells (Fig. 135, 3) have large round bodies and a single spirally coiled process, which arises from a conical projection of the protoplasm. The process often winds about the cell body. Soon after passing through the capsule it acquires a sheath of myelin, and is covered with neurolemma. It may give off collaterals before it divides into its two main branches, which correspond with dendrite and neuraxon respectively. Sometimes the process divides into three branches (Fig. 135, 2); the branching takes place at a node of Ranvier. Certain of the large cells, as found constantly in the human jugular ganglion, lack the coiled windings, so that the process passes directly through the capsule and divides at once into its two branches.

Frequently the ganglion cells are provided with short processes which end in rounded enlargements, either within the capsule (Fig. 135, 5) or outside of it (Fig. 135, 6). Collateral branches may end in this way.

These "end discs" were first observed by Huber in frogs (Anat. Anz. 1896, vol. 12, pp. 417-425). They are found not only in spinal ganglia but also in the central nervous system and in sympathetic ganglia; and after the distal part of a nerve has been cut away, the axis cylinders of the proximal part send out many such buds, which grow into the myelin toward the place of injury. In all cases they are regarded as abortive branches. They are said to occur normally only in adults, and especially in old age, being very numerous in the nodose ganglion of the vagus nerve.


Another feature which, in man, has been found almost exclusively in the nodose ganglion of adults, is the occurrence of "fenestrated cells." These are ganglion cells with peripheral vacuoles, which may break down so that the cell appears multipolar (Fig. 135, 7). Sometimes they are so arranged that the cell process seems to grow out by several roots (Fig. 135,8). Although the fenestrated cells increase in number with advancing age, they are not considered pathological, since they occur in young dogs and other animals.

Less conspicuous than the large cells with medullated fibers, but more numerous, are small pyriform cells with non-medullated fibers (Fig. 135, 4). Ranson, from his own and previous observations, concludes that in the cat and rat, in which the cells have been carefully counted, about two-thirds of the spinal ganglion cells may be classified as small, and are associated with non-medullated fibers (Amer. Journ. of Anat., 1911, vol. 12, pp. 67-87).

FIG. 136. CELLS OF THB HUMAN SYMPATHETIC GANGLIA. (Prepared by L. R. Muller.) A, From the ciliary ganglion; B, from the superior cervical ganglion. X 465.

The spinal ganglion cells are sometimes surrounded by fine networks of non-medullated fibers, which are probably the terminal branches of medullated fibers derived from cells in the sympathetic ganglia (Fig. 135, i). Branches of the sympathetic fibers are also distributed to the blood vessels in the ganglion. Whether any fibers pass through the spinal ganglion without connecting with its nerve cells is still uncertain; they have not been demonstrated in mammals.

Sympathetic Ganglia.

The sympathetic ganglia consist of multipolar cells which are smaller than those of spinal ganglia (Fig. 136). Their round or oval nuclei, often eccentric, have prominent nucleoli and a loose chromatin network, as in other nerve cells; some of them contain two nuclei. The protoplasm is often pigmented. Around the cell bodies, nuclei of the sheath cells may be abundant. Three types of sympathetic ganglion cells are shown in Fig. 137. The motor cells, terminating in contact with smooth muscle fibers, are by far the most abundant (Fig. 137, i). Their neuraxons are non-medullated fibers, which are provided with very slender collaterals. The cell body is stellate and its branching dendrites appear spiny. The second type (Fig. 137, 2) is possibly sensory,


but the terminations of its fibers are not known. Its dendrites are long and slender and may extend from one ganglion to another. Some of them are accompanied by the neuraxon, which may acquire a medullary sheath, often at a considerable distance from the cell body. Cells of the third type (Fig. 137, 3) resemble those of the second type. They have long branching dendrites which pass between the adjacent cells to the periphery of the ganglion, where they form a plexus. Their non-medullated neuroaxones pass out of the ganglion, but their terminations are unknown. Small stellate cells, one of which is shown in the figure, presumably belong with the supporting tissue.

Fibers from the spinal nerves may pass through the sympathetic ganglia, or terminate within them. Thus spinal motor fibers, after losing their myelin sheaths, form pericellular plexuses about the sympathetic motor cells, and their collaterals end in the same way. They are apparently indistinguishable from the sympathetic fibers which pass from one ganglion to another and terminate in pericellular networks. Medullated sensory fibers, some of which arise from lamellar corpuscles, extend through the sympathetic nerves to enter the spinal ganglia.

Chromaffin organs, or paraganglia, are masses or cords of cells which originate in close association with sympathetic ganglia. Although they have often been classed with nervous tissue, they are to be regarded as glands which produce an internal secretion. This secretion acts upon the smooth musculature in the walls of the blood vessels and causes it to maintain a proper state of contraction, or tonus.

When fresh, chromaffin tissue is darkly colored. If preserved in fluids containing chromic acid or salts of chromium, the cells which contain secretion acquire a yellowish-brown stain. The term chromaffin refers to this specific affinity for chromium, and does not mean that the cells stain deeply.

Groups of chromaffin cells are found in connection with the ganglionated trunk of the sympathetic system. In the new-born child these "chromaffin bodies" may reach a length of 1-1.5 mm - (Zuckerkandl) and several of them may be associated with a single ganglion. They are always found in the plexus at the bifurcation of the carotid artery, where they enter into the formation of the carotid gland (glomus caroticum). They occur in vary ing number sin the cceliac, renal and hypogastric plexuses, and extend along the vessels so that chromafnn cells are found in relation with the kidneys, ureters, prostate, epididymis and ovary. The largest bodies (the organs of Zuckerkandl) are found on either side of the inferior mesenteric artery, and may connect with one another by a bridge across the front of the aorta. At birth "the average length of the right one is n.6 mm., and of the left, 8.8 mm." Usually there are two chromaffin bodies on either side in the hypogastric plexus, but the total number of bodies connected with the abdominal plexuses varies greatly, "from 7 to 26, or even more; in one case nearly 70" (Zuckerkandl). Although they undergo regressive changes after birth, they do not dissappear.

The medulla of the suprarenal glands consists of chromafim tissue, which has very important functions throughout life; it will be described in connection with the suprarenal glands.

Structure of Nerves

Nerves are bundles of nerve fibers passing between the central nervous system and the various parts of the body; they are so widely distributed that they may be found in sections of most of the organs and tissues. When examined fresh, in reflected light, nerves are seen to be of two sorts, formerly known as white and gray nerves, respectively. Similarly, sections of the brain and spinal cord are formed of white substance and gray substance. The obvious distinction in color is due to the presence or absence of microscopic sheaths of myelin around the individual fibers. Nerves which contain a large proportion of myelinated or medullated fibers are white; and those which have few are gray. All nerve fibers when first formed are non-medullated, and most of the sympathetic nerves remain in this condition.

Non-medullated nerves can readily be found between the circular and longitudinal layers of smooth muscle in any part of the digestive tube. They are circumscribed bundles of fine fibers running through the coarser connective tissue (Fig. 138). Many of them contain nerve cells, unmistakably characterized by large, round or oval, vesicular nuclei, having a prominent nucleolus. Around the nucleus is dense protoplasm, starting out in branching processes, all but the roots of which are cut away in sectioning. Other cells are found, having relatively small nuclei and very indefinite or wholly imperceptible protoplasmic bodies. These are supporting cells; they produce a syncytial framework in which the nerve cells and their very delicate ramifications are imbedded. The framework tends to form septa, subdividing the nerve into smaller bundles.

FIG. 138. A SYMPATHETIC NERVE FROM THE MYENTERIC PLEXUS OF A CAT. X 77S a., Nucleus of a supporting cell; b., nerve cell; c., non-medullated nerve fibers. Above the nerve are circular smooth muscle fibers in longitudinal section; below it are longitudinal fibers in cross section.

Some non-medullated fibers, but by no means all, are closely invested by sheath cells. According to Schafer, the nuclei of these cells appear to be interpolated in the substance of the fiber, and it is impossible to demonstrate a distinct sheath (Fig. 139). Similarly Bardeen has stated that it is "mainly a matter of judgment to decide whether the fibrils are surrounded by or imbedded within the sheath cells." They correspond with the neurolemma cells of medullated nerves.

Medullated Nerves. The larger sympathetic nerves contain a considerable number of medullated fibers, and the splanchnic nerves are described as white. In the trunks of the spinal nerves, however, the medullated fibers attain their maximum development. Examined with low magnifi

FIG. 139. NON-MEDULLATED NERVE FIBERS. X 4o. (After Schafer.)

cation, such a nerve is seen to consist of round cords imbedded in loose connective tissue (Fig. 140). This loose tissue, which surrounds the entire nerve and its several cords, is the epineurium; its connective tissue bundles are chiefly longitudinal, and are associated with abundant elastic tissue and frequent fat cells; it contains the blood vessels which supply the nerve. Each cord is surrounded by a dense lamellar layer of connective tissue, which contains flattened cells in contact with one another so that they form more or less continuous membranes. This layer is the perineurium. It is continuous with the outer membranes covering the cord, and contains cleft-like spaces which are said to communicate with the subdural and subarachnoid spaces, but which do not connect with lymphatic vessels in the epineurium. Prolongations of the perineurium extend as septa into the larger nerve bundles and constitute the endoneurium, which may penetrate between the individual nerve fibers, forming the so-called "sheaths of Henle." Their nuclei are always outside the neurolemma.


The individual nerve fibers vary in diameter, and the larger ones are probably those which have a longer course. It is impossible to distinguish histologically between sensory and motor fibers. The sheath of myelin which surrounds the fiber varies greatly in thickness, as seen in the cross section, Fig. 141. In ordinary preparations it forms light zones around the dark fibers, suggesting the relation between protoplasm and nucleus; but the rod-like nature of the central fibers is evident on changing the focus. The myelin is surrounded by the membranous neurolemma, within which the single internodal nucleus is occasionally included in a given section. Portions of isolated fibers, viewed longitudinally, are shown in Fig. 142.


Myelin is a mixture of complex fats and lipoid substances, some of which are combined with sugar. Like fat, it is dissolved by ether and blackens with osmic acid. In preserved specimens the emulsion breaks down, giving rise to various forms of shrinkage. A network which appears after fibers have been treated with alcohol and ether is said to be composed of neurokeratin, a substance insoluble in these reagents, which does not blacken with osmic acid. The size of the meshes varies (Fig. 143, A, B). In preparations blackened with osmic acid, the myelin is often traversed by oblique clefts, the incisures of Lantermann (Fig. 143, D). The arrangement of these characteristic clefts

may be pictured by imagining a succession of stemless funnels strung along the axis cylinder, not all of which are pointed the same way. The incisures are doubtless artificial, and their number is increased by pulling the nerve fibers apart; they appear to be empty or crossed by strands of myelin, but in the preparation shown in Fig. 143, C, the neurokeratin framework is so arranged as to correspond with these intervals. In transverse sections, incisures are included in Fig. 143, E and I; the concentric, vacuolated and radial appearances of the myelin are represented in F-H.


A, Axis cylinder; M, medullary sheath (myelin); N, neurolemma; Nu, nucleus of the neurolemma.

The nodes of Ranvier, shown in the diagram, Fig. 131, are conspicuous in isolated nerve fibers stained with osmic acid. Various interpretations of their structure are represented in Fig. 144. According to the first (Fig. 144, A) the myelin occurs like fat, within distinct cells wrapped around the nerve fibers; the node is the interval between successive cells. The nucleus, which is flattened by the myelin against the outer cell wall, mid- way between the nodes, is not shown. Corresponding with the neurolemma on the outside, there is an "axolemma" next the axis cylinder; neurolemma and axolemma come together at the node. If the nerve fibers are treated with silver nitrate, a black precipitate is produced at the nodes, as if an intercellular substance were present; the blackening may extend up the axis cylinder producing cross-shaped figures (Fig. 144, B).

FIG. 143. MEDULLATED NERVE FIBERS. A-D, Longitudinal sections; E-I, cross sections. (A-B, after Gedoelst; C, E, F, after Hardesty; D and I, osmic acid preparations, after Prenant and Scymonowicz; G, alcoholic preservation, after Koelliker H, picnc acid preservation, after Schafer.) a. c., Axis cylinder; in., incisure; my., myelin; nu., nucleus of the neurolemma.

FIG. 144. NODES.

A, Diagram of the intracellular explanation of myelin; B, the cross obtained with silver nitrate; C, the biconical enlargement (after Gedoelst); D, intercellular myelin (after Hardesty) ; a. c., axis cylinder; ax., axolemma; my., myelin; ne., neurolemma; no., node.

As the axis cylinder traverses the node, its fibrils may spread apart, forming a "biconical enlargement." The fibrils in the midst of the enlargement have been described as thickened (Fig. 144, C). The same figure shows no axolemma and suggests that the neurolemma passes across the node without interruption. This is clearly shown in D, where the myelin layer also, though constricted, is not completely divided. The myelin has accordingly been regarded as an exoplasmic part of the axis cylinder, and chemically it is said to be related to the interfibrillar substance or neuroplasm. Bardeen (Amer. Journ. Anat., 1903, vol. 2, pp. 231-257) considers that the myelin is derived from the intercellular substance between the fiber and the sheath, and is "due to influences exerted by the axis cylinder fibrils." That the axis cylinder plays the chief part in its production is indicated by the fact that the myelin breaks down when the fiber degenerates, and that it forms around fibers in the central nervous system where there are no continuous sheaths.

The production of myelin is said to begin at about the fourth month, at the central ends of the nerves. It begins at different times in different tracts and systems, and the medullary sheaths of the spinal nerves are not all formed until two or three years after birth. They continue to increase in thickness into adult life.

Nerve Endings

Sensory Endings

The outward growth of nerve fibers from cells in the ganglia of the spinal and cerebral nerves has already been described. Near their terminations these fibers branch repeatedly at the nodes, lose their myelin sheaths, and form terminal arborizations in contact with epithelial, connective tissue, or muscle cells. These are the sensory endings, and apart from those connected with the eye, ear, and other organs of special sense, they may be described as follows.

Free Endings. Sensory fibers to the epidermis and to the corneal and oral epithelia penetrate the basal layer, passing between the cells as unsheathed fibers, and ramify among the cells in the outer layers (Fig. 145). The extremities of the fibers, which may be pointed or club-shaped, are in contact with the epithelial cells, but do not enter them. In the process of branching the neurofibrils become distributed in smaller and smaller bundles, which often anastomose, forming plexuses; but whether the interlacing constituent fibrils unite with one another so as to form a net has been questioned. At the ends of the branches, each fibril has become separate from the others; frequently it shows varicose enlargements.



Free sensory endings occur not only in stratified epithelia, but also in muscle, tendon and connective tissue. In simple epithelia the free endings may be sensory, but in glandular epithelia they are often efferent fibers, inciting the cells to glandular activity. The ultimate branches of the nerves are so delicate that they cannot be seen in ordinary preparations; they have been demonstrated chiefly by the methylene blue method, applied to very fresh or living tissue.


FIG. 150. THE LEFT PORTION OF FIG. 149. X 345.

In the epidermis, as a modification of the free endADULTCAT.XI35- j n g Sj fib ers are found terminating in disc-shaped networks (tactile menisci) at the base of modified cells (Fig. 147). These tactile cells may occasionally be seen in ordinary preparations.


The stellate "Langerhans cells" shown in Figs. 146 and 147 are usually regarded as wandering cells lodged in intercellular spaces, but Stohr states that intergrading forms connect them with the epithelial cells; and they may act as sensory cells.

Muscle Spindles. As seen in ordinary preparations muscle spindles are shown in Fig. 119 (p. 127). They are slender groups of 3-20 muscle fibers, 1-4 mm. long and 0.08-0.2 mm. wide, around which nerve fibers terminate as shown in Fig. 148. The spindles are surrounded by a thick connective tissue sheath or capsule, continuous with the perimysium, and said to be divided into an -jt inner and an outer layer by a space filled with fluid. The muscle fibers of the spindle are poorly developed. They are distinctly striated toward their tapering and very slender ends, but in their middle portions, sarcoplasm and nuclei are abundant and the striations ill defined. Three or four nerves terminate in each spindle. Their connective tissue sheaths blend with the perimysial capsule, and they branch and lose their myelin as they pass through it to the muscle cells. They may encircle the muscle fibers of the spindle, forming spirals or rings (as in the upper part of Fig. 148), or they may form a panicle of branches with enlarged club-shaped ends. Since they do not degenerate after the motor roots have been cut, they are supposed to be sensory fibers, but their function has not been established. Other sensory fibers to muscle have free endings, as shown in Fig. 157.

FIG. 151. TERMINAL CYLINDER. (After Ruffini, from Ferguson's Histology.) gH, Medullary sheath; il, terminal ramifications of the axis cylinder; L, connective tissue.

FIG 152. TACTILE CORPUSCLE FROM A SECTION OF THE SKIN OF A HUMAN FINGER. X 560. (Prepared by van der Velde, after the Bielschowsky method.)

Tendon Spindles. Tendons possess free sensory endings, together with the tendon spindles. These are small portions of the tendon, 1-3 mm. long and 0.17-0.25 mm. wide, enclosed in sheaths of connective tissue. They stain more deeply than the surrounding tendon.

The few nerve fibers which terminate in a tendon spindle lose their sheaths and branch freely, ending in club-shaped enlargements (Figs 149 and 150). They are found in all tendons and serve to transmit the sensation of tension, being active in connection with coordinated movements. In connective tissue the sensory nerves may have free endings. In addition to these the subcutaneous tissue near the coils of the sweat

glands, and in the corium of the fingers and toes, sometimes contains terminal cylinders (of Ruffini) which resemble tendon spindles in the way that their nerves ramify (Fig. 151). These cylinders lack the distinct capsules which characterize the nerve corpuscles.



Terminal corpuscles are nerve endings consisting of a coarse nerve fiber, or knot of small branches, surrounded by a semifluid intercellular substance (which is granular in preserved tissue), and enclosed in a connective tissue capsule. The terminal ramifications of the nerve show irregular swellings or varicosities, and apparently they unite so as to make a network. Often more than one fiber enters a corpuscle, and it has been suggested that they include afferent and efferent fibers. Generally the connective tissue sheaths of the entering fibers blend with the capsule, and the myelin sheaths are lost just within it. Terminal corpuscles have been grouped as tactile, genital, bulbous, articular, cylindrical, and lamellar.

Tactile corpuscles (or Meissner's corpuscles) are elliptical structures, 40-100 n long and 30-60 n broad (Fig. 152). They are characterized by transverse markings, due to the corresponding elongation of the capsule cells and the tactile cells within. From one to five medullated fibers enter the lower end of a tactile corpuscle, losing their sheaths soon after entering. They pursue a spiral course through the corpuscle, giving off branches which end in enlarged terminal networks between and upon the tactile cells. These corpuscles are found in some of the papillae, or connective tissue elevations just beneath the epidermis, being especially numerous in those of the soles and palms (23 in i sq. mm.) and in the finger tips; they occur also "in the nipple, border of the eyelids, lips, glans penis and clitoris."

Genital corpuscles are large, round or oval bodies 60-400 n long (Fig. 153) which may receive as many as ten nerve fibers. These ramify and send branches to neighboring corpuscles, and also to the epidermis. The genital corpuscles are deeply placed be- FlG neath the epithelium of the glans penis, clitoris, and adjoining structures.

Bulbous corpuscles (of Krause) are smaller than the genital corpuscles, having a diameter of 20-100 n (Fig. 154). They are most numerous (1-4 in a sq. mm.) in the superficial connective tissue of the glans penis and clitoris. Similar structures, either round or oval, are found in the conjunctiva and "edge of the cornea, in the lips and lining of the oral cavity, and probably in other parts of the corium." They have thinner

capsules and receive fewer nerves than the genital corpuscles, which they resemble. The articular corpuscles, found near the joints, belong in the same category.

Cylindrical corpuscles (cylindrical end bulbs of Krause) contain a single axial nerve fiber with few or no branches, terminating in a knob-like or rounded extremity (Fig. 155). The fiber is surrounded by a semi-fluid substance, sometimes described as an inner bulb, and this is enclosed in a few concentric layers of cells which are continuous with the sheath of the nerve. Cylindrical corpuscles are found in the mucous membrane of the mouth and in the connective tissue of muscles and tendons.

Lamellar corpuscles (or Pacinian corpuscles) are macroscopic elliptical structures 0.5-4.5 mm. long and 1-2 mm. wide (Fig. 156). They were first observed in dissections, as minute vesicular bodies attached to the terminal branches of nerves. Microscopically they are striking objects ; suggesting an encysted foreign body. The axial core of the corpuscles is surrounded by concentric layers, sometimes as many as fifty, which represent a perineurium distended with fluid. A single large nerve fiber enters one end of the corpuscle and loses its myelin as it traverses the lamellae. It extends through the semifluid core without obvious branches, sometimes being flattened and band-like; it may fork at its further end or form a coil of branches, and it has been observed to pass out and enter another such corpuscle. Usually the corpuscles are sectioned obliquely or transversely so that the concentric layers completely encircle the inner core.

FIG. 156. SMALL LAMELLAR CORPUSCLE FROM THE MESENTERY OF A CAT. X so. The nuclei of the capsule cells appear as thickenings. The myelin of the nerve fiber may be traced to the inner core.

Special methods have shown that the axial fiber may possess many short lateral branches ending in knobs, and that one or more delicate fibers may enter (or leave) the corpuscles in addition to the large one just described; they form a net surrounding the axial fiber. A small artery may pass into the corpuscle beside the nerve and supply the lamellae with capillaries. Lamellar corpuscles are abundant in the subcutaneous tissue of the hand and foot and occur in other parts of the skin, in the nipple, and in the territory of the pudendal nerve; they are found near the joints (particularly on the flexor side) and in the periosteum and perimysium, in the connective tissue around large blood vessels and nerves, and in the tendon sheaths; also in the serous membranes, particularly in the mesenteries. According to Schumacher (Arch. f. mikr. Anat, 1911, vol. 77, pp. 157-191) the lamellar corpuscles become inflated when the blood-pressure is increased, and "their structure and distribution, together with the results of experiments, indicate that they are regulators of the blood pressure."


Motor Endings

The motor nerve endings are the terminations of efferent nerves, in contact with smooth, cardiac or striated muscle fibers. The nerves to the smooth muscles are a part of the sympathetic system. They are non-medullated fibers which branch repeatedly, forming plexuses. From the plexuses very slender varicose fibers proceed to the muscle cells, in contact with the surface of which they end in one or two terminal or lateral nodular thickenings. Probably each muscle cell receives a nerve termination. Except that the nerve endings in heart muscle are a little larger, often provided with a small cluster of terminal nodules, they are like those of smooth muscle.

Striated muscles are innervated

by the neuraxons of the ventral roots, B

which grow out from cell bodies re- L FlG IS8 ._ MOTOR PLATES

Within the Central System. A > Surface view, from a guinea-pig; B, vertical

section, from a hedgehog. (After B6hm and von Davidoff.) g., Granular substance of the

lorm piexubt motor p]ate . m ^ striat?d muscle . n . t nerve

fibers in the perimysium, from which terminal ramifications f the ne branching medullated fibers extend into the fasciculi (Fig. 157). Each muscle fiber receives one of these branches, or sometimes two placed near together. They are usually implanted near the middle of the muscle fiber. The connective tissue sheath of the nerve blends with the perimysium, and the neurolemma is said to be continuous with the sarcolemma. On the inner side of the sarcolemma the myelin sheath ends abruptly, and the nerve fiber ramifies in a granular mass considered to be modified sarcoplasm, which may contain muscle nuclei. This entire structure appears as a distinct elevated area, estimated to average from 40 to 60 n in diameter; it has been named the motor plate. A surface view and a section of a motor plate are shown in Fig. 158.

Vascular Tissue

Vascular tissue includes the blood vessels, the heart, and the lymphatic vessels, together with the blood and the lymph.

Blood Vessels

General Features

The existence of blood vessels was well known to the ancient anatomists, and a distinction was sometimes made between pulsating and non-pulsating vessels. They were all included by Aristotle under the term <\ty (vein). He described the two great vessels at the back of the thorax, one of which is the vena cava; the other, as he states, "by some is termed the aorta, from the fact that even in dead bodies part of it is observed to be full of air." He added that " these blood vessels have their origins in the heart, for in whatever direction they happen to run, they traverse the other viscera without in any way losing their distinctive characteristics as blood vessels; whereas the heart is, as it were, a part of them" (Historia Animalium, Book 3, trans, by Thompson). Subsequently the term artery was applied to the aorta and its branches, which were found partly empty of blood after death, and were believed to convey air; the windpipe was called the arteria as per a.

Vesalius described an artery as "a vessel similar to a vein, membranous, round, and hollow like a pipe, by means of which vital spirit and warm blood, rushing impetuously, are distributed throughout the entire body; by the aid of these, and thus through the motion of the artery itself (which is by dilatation and contraction) the vital spirit and the natural warmth of the several parts are renewed" (De corporis humani fabrica, 1543, 4th ed., 1604). Vesalius described the arteries and veins as composed of coats (tunica) in which he found loose tissue and layers of fibers circular, oblique, and longitudinal.

The valves of the veins, consisting of thin membranes projecting into their lumens, were first described and clearly figured by Fabricius, under whom Harvey studied at Padua (De venarum ostiolis, 1603). Fabricius observed that the ostiola are found chiefly in the veins of the limbs and are "open toward the roots of the veins but closed below." He considered that "to a certain extent they hold back the blood, lest like a stream, it should all flow together either at the feet, or in the hands and fingers." He stated that the veins can be easily dilated and distended, since they are composed of a simple and thin membranous substance; and concluded that the veins have valves to prevent over-distention, but the arteries, because of the thickness and strength of their walls, do not require them.

In demonstrating the circulation of the blood (in 1628) Harvey contributed little to the knowledge of the structure of the vessels. He could not find the microscopic connections between the arteries and veins, but they were discovered not many years later by Malpighi (De pulmonibus, Ep. II, 1661). In the membranous lungs of frogs and turtles, Malpighi found a rete or network of vessels connecting the artery and vein, so that the blood was not poured out into spaces, but was driven through tubules. He concluded that if in one case the ends of the vessels are brought together in a rete, similar conditions exist elsewhere, and he observed the circulation taking place in the diaphanous anastomosing vessels of the distended bladder of frogs. Leeuwenhoek (1698) clearly figured the minute vessels which pass from the arteries to the veins in the caudal fin of eels, and noted that the line of separation between the artery and vein is arbitrary.

The vessels which connect the arteries with the veins, because of their hair-like minuteness, were later called capillaries. Physiologically they form the most important part of the vascular system, and anatomically they are the most fundamental. They consist merely of endothelial tubes. All larger vessels, not only the arteries and veins, but also the heart, are derived from endothelial tubes and retain their endothelial lining. The endothelium, however, becomes surrounded by layers of smooth muscle fibers and connective tissue, which form the substance of the vessel walls. The arteries in general have thicker and more elastic walls than the veins, and tend to remain open after death; the thinner walls of the veins are prone to collapse.


In an early stage the blood vessels of the embryo form a network in the splanchnopleure. In mammals, as in the chick (Figs. 27 and 28, p. 40), the portion of the net nearest the median line forms, on either side of the body, a longitudinal vessel, the dorsal aorta. The part of the net folded under the pharynx constitutes successively (beginning posteriorly) the vitelline veins, the heart, and the ventral aorta, and the latter are continuous in front of the pharynx with the dorsal aortae. The heart first appears as two dilated vessels, one on either side, which are parts of the general network. They are brought together in the median line under the pharynx and fuse. At first the heart pulsates irregularly, but with the establishment of the circulation, its beats become rhythmical. The blood flows from the general network through the veins to the heart, and thence through the arteries back to the net. All the future vessels of the body are believed to be offshoots from the endothelial tubes just described. They grow out, as shown in Fig. 159, through the mesenchyma with which they often appear to be inseparably connected. The sprouts are at first solid, but soon become hollow except at the growing tips. They may encounter similar offshoots from the same or other vessels and fuse with them. Through the anastomosis of such sprouts new capillary nets are produced.

The formation of a definite system of arteries and veins out of a general network may be partly explained on mechanical principles. The vascular outgrowths must take certain courses marked out by the epithelial structures. Thus in early stages they may grow between the somites, but not into them, producing a series of segmental vessels; they pass around the front of the fore-gut and up and down between its lateral outpocketings, so that the regular system of aortic arches appears to depend upon these epithelial obstructions; and they are guided along the under surface of the developing brain in a very characteristic manner. Epithelial obstructions therefore determine the position of the capillary plexuses. In each plexus the favorable channels enlarge and become the main arteries and veins, sending forth new branches and acquiring thick walls; whereas the vessels in which the current is slow remain small or disappear.

FIG. 159 Blood vessels from a rabbit embryo of 13 days, developing as endothelial sprouts (en) from pre-existing vessels (b.v.); b.c., blood corpuscle within a vessel.

These factors are further considered by Thoma (Histomechanik des Gefasssystems, 1893).

The way in which main trunks develop from indifferent networks has been described by Evans on the basis of extraordinarily perfect injections; thin fluid introduced into the vessels of a living chick embryo is distributed throughout the vascular system by the action of the heart (Anat. Rec., 1909, vol, 3, pp. 498-518). Obviously however if vessels are arising as mesenchymal spaces which subsequently become joined to the vascular system, they would not be revealed by this method. The existence of detached spaces in rabbit embryos has been denied by Bremer, after making very careful graphic reconstructions of all the vessels in the anterior end of the specimens studied. He finds that a network consisting largely of solid strands precedes the network of open tubes (Amer. Journ. Anat., 1912, vol. 13, pp. 111-128). Schafer, however, describes the formation of vessels by the vacuolization of connective tissue cells, which then become connected with processes from pre-existing capillaries, and so added to the endothelium. He states that "a more or less extensive capillary network is often formed long before the connection with the rest of the vascular system is established" (Text-book of Micr. Anat., 1912). His observations were made upon subcutaneous tissue of the new-born rat. Similar appearances in the subcutaneous tissue of human embryos may be interpreted quite differently, and before it can be accepted that the cells containing red corpuscles are detached from the vascular system, careful reconstructions are required.

The formation of anomalous vessels readily takes place by the persistence and enlargement of channels usually unfavorable. This is discussed by S. R. Williams in explaining the condition observed in an adult salamander, in which one of the long and slender lungs received its artery at the anterior end and the other at the posterior end (Anat. Rec., 1909, vol. 3, pp. 409-414). Innumerable forms of human vascular anomalies may thus be explained embryologically; some of them represent persistent vessels which are normally important at a certain stage of development, and others represent connections which are as abnormal in the embryo as in the adult (cf. Lewis, Amer. Journ. Anat., 1909, vol. 9, pp. 33-42).

A very characteristic form of circulation occurs in certain organs, in which the endothelium of the vessel walls is closely applied to the epithelium of the secreting tubules, or other parenchymal structure (Fig. 160). The walls of the vessels are as thin as those of capillaries, but their diameter is much greater, so that they have been described as lacunar vessels or "sinusoids," the term sinus being generally applied to the large thin-walled veins in the dura mater about the brain (Minot, Proc. Boston Soc. Nat. Hist., 1900, vol. 29, p. 185-215). Apparently the close apposition of the endothelium, on all sides, to the cells of the parenchyma is the most essential characteristic of these vessels and must be of considerable physiological significance. There are few or no connective tissue cells between the thin lining of the vessel and the epithelial tissue which it nourishes. Capillaries, on the contrary, are imbedded in connective tissue, even though occasionally they approach close to an epithelium, sometimes appearing to enter it. In the lungs the capillaries are compressed between epithelial plates, but they do not resemble the vessels shown in Fig. 160.

Where sinusoids are most highly developed, as in the liver and Wolffian body of embryos, they possess another very significant characteristic. They are not connections between an artery and a vein, like the capillaries, but are subdivisions of veins. Thus in the liver, as shown in the diagram, Fig. 161, the portal vein enters the organ and is subdivided by cords of hepatic cells into sinusoids, such as are shown in section in Fig. 160. These reunite to empty into the vena cava inferior. The sinusoids


FIG. 160. SINUSOIDS (Si) IN THE LIVER OF A CHICK EMBRYO OF ELEVEN DAYS. (Minot.) h.c., Cords and tubules of hepatic cells.

of the liver have therefore been described as formed by the intercrescence of vascular endothelium and hepatic parenchyma. This arrangement of veins constitutes the hepatic portal circulation, taking its name from the entering vessel. The same type of venous circulation occurs in the Wolffian bodies, where it constitutes the "renal portal circulation," although it has no connection with the portal vein. It is probable that this form of circulation, which is generally lacunar or sinusoidal, represents a primitive type of vascularization, since a single vessel passing by or through an organ provides it with both afferent and efferent vessels. The arterio-venous circulation requires the presence of two vessels with currents flowing in opposite directions. There are indications that various organs in the human embryo have a transient "portal circulation" before the arteries connect with the network and become the main afferent channels.



The connective tissue is represented by dots. Ar., Artery; Int., intestine; V., vein; V. C. I., vena cava

inferior; V. P., portal vein.


The capillaries are endothelial tubes of varying diameter, the smallest being so narrow that the blood corpuscles must pass through them in single file. Their walls are composed of elongated, very flat cells, with irregularly wavy polygonal outlines which are clearly demonstrated in silver nitrate preparations (Fig. 162). Between the cells, the red and white corpuscles frequently make their way out of the vessel. There are no pre-formed openings for this purpose, and the endothelial cells come together after the corpuscles have passed out. Certain endothelial cells are phagocytic, devouring objects which float in the blood; some of them may become detached and enter the circulation. Moreover endothelial cells are contractile, and may be stimulated to activity

by the sympathetic fibers in the delicate perivascular plexus which is shown in methylene blue preparations. Some of the fibers end in contact with the cells and presumably control the caliber of the vessel; other fibers may be afferent and receive a stimulus when the vessel expands and stretches the plexus. The bulging of endo PREPARATION. (A fter Koelliker) *,-, , . .1 i e ir

thelial nuclei into the lumen of vessels, frequently seen in preserved specimens, is probably due to post-mortem contraction; in life the lining is presumably smooth.

Although capillaries vary in diameter (4.5-12 /i), those in a given territory are quite uniform, both as to caliber of individual vessels and the size and pattern of the meshes in the network. The closest meshes and largest capillaries occur in secretory organs and in the lungs, which are therefore abundantly supplied with blood. The muscles are well supplied by slender capillaries in a rectangular meshwork. Serous membranes and dense connective tissue have a scanty blood supply, from narrow capillaries in a coarse net.


The walls of the arteries are composed of three layers the tunica iniima, tunica media, and tunica externa, respectively. The intima includes the endothelium and generally an underlying elastic membrane, separated from the endothelium by a small amount of fibrous tissue. The media is primarily a layer of circular smooth muscle fibers; and the externa (formerly called the tunica adventitia) consists chiefly of connective tissue. The thickness of all these layers is greatest toward the heart. They become thinner at the places where the arteries branch, and in the pre-capillary vessels nothing remains but the endothelium.

The small terminal arteries are called arterioles. They are endothelial tubes encircled by scattered smooth muscle fibers. In Fig. 163, C, the oval nuclei of the endothelium are seen to be elongated parallel with the course of the vessel. As is usually the case, the walls of the endothelial cells are not visible. The rod-shaped nuclei of the muscle fibers are at right angles with the axis of the vessel. In the somewhat larger artery, B, the muscle fibers form a single but continuous layer, the media, outside of which the connective tissue is compressed to make the externa. Its fibers tend to be parallel with the vessel. The walls of such an artery are so thick that it is possible to focus on the layers separately; thus in A, the endothelium, which with a delicate elastic membrane beneath it constitutes the intima, is not seen, being out of focus. The nuclei of the media and externa are evident. A cross section of such a vessel is seen in Fig. 177.


i, Nuclei of endothelial cells; m, nuclei of circular muscle fibers; a, nuclei of connective tissue. In A, since the endothelium is out of focus, its nuclei are not seen.

The larger arteries are lined with endothelium similar to that of the capillaries, as shown in silver nitrate preparations (Fig. 164). This endothelium rests on a layer of connective tissue containing flattened cells and a network of fine elastic fibers. The meshes of the fibrous and elastic tissue are elongated lengthwise of the vessel, and on surface view they present a longitudinally striped appearance, f In addition to this subendothelial tissue and the endothelium, the intima includes the inner elastic membrane (Fig. 165). This is usually a conspicuous layer thrown into wavy folds by the post-mortem contraction of the vessel. It is easily seen with ordinary stains, appearing as a refractive layer, and is deeply colored by resorcin-fuchsin and other elastic tissue stains (upper segment in Fig. 165). In smaller arteries the endothelium appears to rest directly upon the elastic network which replaces this membrane; and in such large ones as the external iliacs, the principal branches of the abdominal aorta, and the uterine arteries in young persons, the subendothelial tissue is said to be lacking. The inner elastic membrane is not a continuous sheet of tissue, since it is perforated by elongated apertures; it forms a


This portion is shown enlarged on the left.


a, Circular, and b, radial elastic fibers of the media of the artery; c, external elastic membrane; d, elastic

fibers in the media of the vein; e, circular, and g, longitudinal muscle fibers of the media; f, endothelium.

fenestrated membrane and the development of such membranes from elastic networks has already been described (cf. Fig. 54, p. 67). The membrane is particularly thick in the larger arteries of the brain, and it is sometimes double.

The media, which consists of but a single layer of circular muscle fibers in the pre-capillary vessels, becomes many-layered in larger arteries. Generally the fibers are all circular or perhaps oblique, but in the loose musculature of the umbilical arteries, longitudinal fibers are numerous. Longitudinal fibers are said to occur in certain other vessels near theintima, being especially well developed in the subclavian artery. The post-mortem contraction of the circular fibers, which throws the intima into folds, causes a spiral crumpling of certain muscle nuclei, the significance of which has already been discussed (Fig. 106, p. 117). Between the muscle fibers there are circular elastic fibers, or plates in the larger vessels, which are thrown into wavy folds. Radial fibers, which connect these in a general network, are slender and require special staining. White fibers are present, apparently formed in considerable part by the muscle fibers which they bind together. The proportion between the muscular and elastic tissue in the media varies in different arteries. In the smaller vessels, the muscular tissue predominates, and this is true also of the cceliac, femoral and radial arteries. But in the common iliac, axillary and carotid arteries the elastic tissue prevails, and in this respect they resemble the largest arteries the aorta and pulmonary artery.

The externa is a connective tissue layer which sometimes contains scattered bundles of longitudinal muscle fibers. It has many longitudinal elastic fibers, which are particularly numerous toward the media, where they are often grouped as the external elastic membrane (Fig. 165). This is not a fenestrated membrane, but is merely a dense zone of longitudinal fibers. It is said to be well developed in the carotid, brachial, femoral, cceliac and mesenteric arteries, and to be absent from the basilar and other cerebral arteries.

Nerves and vessels ramify in the externa. The walls of the larger arteries are supplied with small blood vessels, the vasa vasorum, derived from adjacent arteries. These are distributed chiefly to the externa; they may penetrate the outer part of the media but do not reach the intima. Lymphatic vessels form perivascular plexuses, and send branches into the externa. The nerves are medullated and non-medullated. They include vasomotor fibers which innervate the smooth muscle cells, and sensory or afferent nerves which have terminal arborizations in the intima and in the externa. Other nerve fibers end in lamellar corpuscles in the externa of the aorta and other large vessels.

Ganglia are not seen in the walls of the vessels, and the sympathetic fibers to the muscles therefore travel considerable distances to their terminations. In this respect the nerves to the smooth muscles of the vessels differ from those to the musculature of the digestive tube.

In the largest arteries (the aorta and pulmonary arteries) the intima is very broad (Fig. 166), and it increases in thickness with age. Its endothelial cells are less elongated than those of smaller arteries. They rest on a fibrous subendothelial tissue, containing flattened stellate or rounded cells, and networks of elastic tissue/- The elastic fibers are thicker toward the media, finally producing a fenestrated membrane which corresponds with the inner elastic membrane of smaller vessels, but which is scarcely thicker than adjacent elastic lamellae. The broad media consists of elastic membranes and muscle fibers, but the elastic tissue greatly predominates. On section the wall of the fresh aorta consequently appears yellow, and not reddish like the more muscular walls of smaller arteries. The elastic tissue is arranged in a succession of circular fenestrated membranes connected with one another by oblique fibers. Between them are the muscle cells. According to Koelliker, in the inner layers of the media, the muscle cells form an anastomosing syncytium

of short, broad and flattened elements, somewhat resembling cardiac muscle (Fig. 167), but in the outer layers the fibers are of the ordinary type. The externa contains no outer elastic layer and is relatively thin; its inner elastic portion may have been taken over into the media.


Since the artery to any structure and the returning vein are often side by side, they are frequently included in a single section and may readily be compared. In embryos the veins are of much larger diameter than the corresponding arteries, and they have thinner walls. Although the difference in diameter is less marked in the adult, it generally remains a distinctive feature (Fig. 177, p. 186), and the difference in the thickness of the walls becomes accentuated (Fig. 165). In comparing the diameters of the ulnar vein and artery in Fig. 165, it should be remembered that the ulnar artery is usually accompanied by two returning veins, only one of which is shown in the figure. Because of their thinner walls, which contain relatively little elastic tissue, the veins are generally partly collapsed; the lumen is therefore irregular, whereas that of the arteries tends to be round (Fig. 165). Small veins full of blood may be round, however, and the arteries are sometimes irregularly contracted.


a, Endothelium; b, subendothelial fibrous tissue; c, d, elastic membranes of the media.


This portion is enlarged below Endothelium.

The walls of the veins, like those of arteries, are composed of three layers, the intima, media, and externa. The intima includes the primary endothelium, which is composed of polygonal cells, generally shorter and broader than those of arteries. The endothelium rests on a thin layer of subendothelial fibrous tissue. The inner elastic membrane of arteries is represented in the smaller veins by a thin homogeneous membrane, but in larger veins it is replaced by a network of elastic fibers (Fig. 165). In addition to these structures the intima of certain veins contains scattered oblique and longitudinal muscle fibers; they are said to occur in the iliac, femoral, saphenous and intestinal veins, the intramuscular part of the uterine veins, and especially in the dorsal vein of the penis near the suspensory ligament.

The media shows great variations. It is generally a thin layer consisting of circular muscle fibers, elastic networks and relatively abundant connective tissue, and is best developed in the veins of the lower extremity (especially the popliteal). In those of the upper extremity it is not so well marked, and it is still thinner in the larger veins of the abdominal cavity; it is reduced to fibrous tissue and is essentially absent from the vena cava superior, the veins of the retina, of the pia and dura mater, and of the bones.

The externa is the most highly developed layer of the veins. It consists of interwoven bundles of connective tissue, elastic fibers, and longitudinal bundles of smooth muscles which are more abundant than in the arteries. In certain veins (e.g., the main trunk of the portal, the renal and suprarenal veins) the longitudinal muscle forms an almost complete layer of considerable thickness (Fig. 168).

FIG . 168 . A CROSS SECTION OF A HUMAN SUPRARENAL VEIN, STAINED WITH H^KMATOXYLIN. X 240. , Circular muscle fibers of the media; b, connective tissue; c, d, longitudinal muscle fibers of the externa; e, connective tissue; f, small vein; g, fat cell.

The valves of veins are paired folds of the intima, each shaped like half of a cup attached to the wall of the vein so that its convex surface is toward the lumen. In longitudinal section they appear like the valves of the lymphatic vessel shown in Fig. 179. The valves are generally found distal to the point where a branch empties into the vein, and they prevent its blood from flowing away from the heart. They are most numerous in the veins of the extremities, but appear also in the intercostal, azygos, spermatic, and certain other veins; none are found in the vertical trunks of the superior and inferior venae cavae. They counteract the effects of gravity upon the blood, and it has been suggested that their arrangement in man corresponds rather to a quadrupedal attitude than to an upright position. The endothelial cells on the surface of the valve toward the lumen of the vein are elongated parallel with the current, and beneath them there is a thick network of elastic tissue. On the side of the valve toward the wall of the vein, the long axis of the cells is transverse, and there the cells rest upon fibrous connective tissue.

The Heart


The heart has already been described as a median longitudinal vessel situated beneath the pharynx, formed posteriorly by the union of the vitelline veins, and terminating anteriorly in the two ventral aortae (Figs. 27 and 28, p. 40). This endothelial tube is surrounded by the mesothelium of the body cavity, except along its dorsal border, where it is attached, as it were by a short mesentery, to the under side of the fore-gut. If the embryo is placed in an upright position, corresponding with that of the adult, the relations of the heart to the body cavity will be as shown in the diagram, Fig. 169, A. The posterior part of the body cavity, which becomes the peritoneal cavity, extends forward on either side and comes together across the median line beneath the heart, thus forming the pericardial cavity. As the heart develops it becomes bent upon itself as shown in Fig. 169, B; and below it, a shelf of tissue forms across the body, representing the future diaphragm. Dorsal to the diaphragm, the pericardial cavity still communicates with the peritoneal cavity, on either side of the body. In the region of this communication the lungs later develop, and partitions separate the part of the body cavity around them, namely the pleural cavity, from the pericardial and peritoneal cavities respectively. These partitions are the pleuro-pericardial membrane and the membranous part of the diaphragm (Fig. 169, C). Meanwhile the mesentery of the heart has become thin and has ruptured in the hollow of the Ushaped bend, forming the sinus transversus pericardii, which persists throughout life as a small but very definite structure.

While the heart is still a simple tube consisting of endothelium internally and mesothelium externally, with a space between them bridged by protoplasmic strands, it beats regularly, although possessing neither nerves nor muscles. Without causing any interruption of the circulation the simple tube becomes divided into four chambers, namely the right and left atria (or auricles 1 ) and the right and left ventricles. The process of subdivision may be outlined as follows:

When the tube becomes bent into a U, the venous end of the heart is carried anteriorly, dorsal to the aortic end, as shown in Fig. 170, A-C.


A.., Aortic end of heart; B. W., body wall; D., diaphragm; Ht., heart; Li., liver; Lu., lung; P. C., pericardia! cavity: Per., peritoneal cavity; PI., pleural cavity; S.p-p., pleuro-pericardial septum, S. tr. p., sinus transversus pericardii; V., venous end of the heart.

At the same time the ventral or aortic limb of the U is carried to the right of the median plane (C). The dorsal limb is divided into two parts by an encircling transverse constriction, the coronary sulcus (s.c.}. Its thickwalled portion, ventral to the sulcus, forms the ventricles; the thin-walled dorsal portion becomes the atria. In the human embryo of three weeks (C) the atria are represented by a single cavity subdivided into right and left parts only by an external depression in the median plane. The right portion receives all the veins which enter the heart (the vitelline veins and their tributaries) and is much larger than the left portion. The cavities of the atria not only freely communicate with each other but they have a common outlet into the undivided ventricle. From the ventricle the blood flows out of the heart through the aortic limb. In a complex manner, described in text-books of embryology, a median septum develops, dividing the heart into right and left halves.

In the heart of a i2-mm. pig embryo this septum has already formed (Fig. 170, D) and has been exposed by cutting away most of the left atrium and left ventricle. The septum between the atria becomes perforated as it develops, so that in embryonic life the atria always communicate. The perforation in the septum is the foramen ovale.

  • 1 According to the anatomical nomenclature adopted at Basle, the term auricle (diminutive of auris, ear) is restricted to what was formerly called the auricular appendix, and the term atrium (chamber) is used for the cavity as a whole.

Encircling the orifice which connects each atrium with the corresponding ventricle, the is a ring of mesenchyma which in the adult becomes dense fibrous tissue the annulus fibrosus. Extending from this ring into the left ventricle there are two flaps of tissue partly detached from the ventricular walls. They constitute the bicuspid valve (or mitral valve). Toward the apex of the heart each flap passes into strands of tissue attached to the walls of the ventricle. These strands become the chorda tendinae B of the adult, and the muscular elevations into which they are inserted are the papillary muscles (musculi papillares). The differentiation of these structures has not taken place in the stage shown in Fig. 170.


A and B, From rabbits nine days after coitus; C, from a human embryo of three (?) weeks; D and E, from a 12-mm. pig (D sectioned on the left of the median septum, and E on the right of it); F, from a 13.6mm. human embryo, sectioned like E. The hearts are all in corresponding positions with the left side toward the observer, the anterior end toward the top of the page, the dorsal side to the right, ao., Aorta; c. s., coronary sinus; f. o., foramen ovale; i. f., interventricular foramen; 1. a., left atrium; p. a., pulmonary artery; p. v., pulmonary vein; r. a., right atrium; s., septum membranaceum separating the root of the aorta from tne right ventricle; s. c., coronary sulcus; v., ventricle; v. b., bicuspid valve; v. t., tricuspid valve; v. v., vitelline vein; v. v. s., valves of the venous sinus.

In the i2-mm. pig (Fig. 170, D) the median septum which has grown up from the apex of the heart, so as to separate the right and left ventricles from each other, is not complete. The ventricles still communicate through the interventricular foramen, and through this aperture the blood passes from the left side of the heart to enter the root of the aorta. The root of the aorta is shown in E, a section of the same heart made on the right of the median septum. The pulmonary artery and the part of the aorta near the heart develop first as a single vessel; they become separated from one another by the formation of a partition. As long as the dividing wall is incomplete, the blood from either ventricle may pass out through either artery as shown in E. In the more advanced human embryo, F, the partition between the aorta and pulmonary artery has extended so that it joins the interventricular septum, and causes the interventricular foramen to open into the root of the aorta only (s). This portion of the interventricular wall which is the last to form, is translucent in the adult, and is known as the septum membranaceum.

As previously noted all the veins come together to enter the right atrium. The original vitelline veins are no longer directly connected with the heart, and their persistent cardiac outlet becomes the terminal part of several large branches. These are the superior vena cava from the head and arms, the inferior vena cava from the trunk and legs (receiving as branches the hepatic vein draining the portal system from the intestine, and the umbilical vein from the placenta); and the coronary sinus which, as it passes across the heart in the coronary sulcus, receives branches from the wall of the heart. All these veins come together in a cavity, ill defined in mammals, known as the sinus venosus, and this sinus empties into the right atrium through an orifice guarded by a valve with right and left flaps. With further growth the sinus venosus becomes a part of the atrium, and the superior and inferior venae cavse and coronary sinus open separately, guarded by imperfect valves derived from the valves of the sinus venosus. The left flap of this valve is said to assist in closing the foramen ovale; the right flap becomes subdivided into the rudimentary valve of the vena cava inferior (Eustachian valve) and the valve of the coronary sinus (Thebesian valve). The degeneration of the valve of the venous sinus seems to take place after the bicuspid and tricuspid valves have become well formed, and have superfluous. In early stages it must be regarded as the principal valve of the heart. The tricuspid valve, between the right atrium and right ventricle, develops from the cardiac walls in the same way as the bicuspid valve. Their formation is discussed by Mall (Amer. Journ. Anat., 1912, vol. 13, pp. 249-298).

In the embryonic heart, the left atrium receives most of its blood through the foramen ovale, but the pulmonary veins early grow out from it as a small vessel (Fig. 170, D) which sends four branches to the lungs. These are given off near the heart, and with the enlargement of the atrium they come to open into it separately. After birth they are the only supply of the left atrium, and they convey the same quantity of blood as the veins which enter the right atrium.

Layers Of The Heart

Early in the development of the heart a third layer, consisting of mesenchyma, forms between the endothelium and mesothelium. It gives rise to the cardiac musculature, and toward the primary layers it produces connective tissue! The wall of the heart

in the adult is divided into three layers, the endocardium, myocardium and epicardium respectively. The endocardium consists of the endothelium, which is continuous with that of the blood vessels, and of subendothelial fibrous tissue. According to Mall, this tissue is derived from the endothelium. The myocardium is the muscle layer, which is thin in the atria, but very thick in the ventricles; in the left ventricle it is much thicker than in the right. The epicardium consists of the pericardial epithelium together with underlying connective tissue. This layer is also called the visceral pericardium, and with the parietal pericardium it bounds the pericardial cavity, forming a closed sac containing the pericardial fluid. The general relations of these layers in an embryonic heart are shown in Fig. 171. The epicardium is a smooth layer. The musculature of the ventricles is arranged in trabeculae covered with endothelium, between which there are blood spaces classed as sinusoids. In the adult the musculature is more compact, but internally it is indented by many clefts and irregular spaces, extending among the trabecula carnecs and the conical papillary muscles.

Endocardium. The endocardium consists of endothelium which is a single layer of flat, irregularly polygonal cells, and of the underlying connective tissue which contains smooth muscle and many elastic fibers (Fig. 172). Elastic fibers are more highly developed in the atria than in the ventricles; they occur either as networks of thick fibers or fuse to form fenestrated membranes. Smooth muscle fibers are more numerous where the wall of the heart is smooth; they are most abundant in front of the root of the aorta.

The atrio- ventricular valves are essentially folds of endocardium containing dense fibro-elastic tissue continuous with the similar tissue in the annuli fibrosi. The valves contain muscle fibers toward these rings, and elastic fibers which are prolonged into the chorda tendinea. Blood vessels are found only in the basal portion of the valves, where the muscle fibers occur. The semilunar valves of the pulmonary artery and aorta contain neither muscle fibers nor vessels. Their elastic fibers are found chiefly on the ventricular sides of the valve, and in the noduli (which are thickenings in the middle of the circumference of each segment, to perfect their approximation when closed).


ca., Capillaries; en., endothelium; 1. a., left atrium; 1. v., left ventricle; mes., mesothelium (of the epicardium, or visceral pericardium) ; p. c., pericardial cavity; p. p., parietal pericardium; r. a., right atrium; r. v., right ventricle; si., sinusoids; v.b., bicuspid valve; y. t., tricuspid valve; v. v. s., valves of the venous sinus.

Myocardium. The myocardium consists of muscle fibers arranged I in layers or sheets, which are wound about the ventricles in complex spirals, I making a vortex at the apex of each ventricle. If the heart is boiled in dilute acid these layers may be unwound, and the heart has frequently been investigated in this way, most recently by Mall (Amer. Journ. Anat., 1911, vol. n, pp. 211-266). The layers are composed of cardiac muscle, which is a syncytium of striated fibers with central nuclei and intercalated discs, as already described (p. 129). Cardiac muscle is shown in longitudinal section in Fig. 121 (p. 129), and in transverse section in Fig. 172. Between the muscle fibers there are capillary branches of the coronary vessels which ramify in the epicardium. The capillaries come into close relation with the muscle fibers and some of them extend into the endocardium. Certain vessels, especially in the right atrium, empty into the cavity of the heart as small veins known as the vena minima (or veins of Thebesius). Minute veins in the papillary muscles have been described as opening into the ventricle at both ends.

FIG. 172. FROM A CROSS SECTION OF THE PECTINATE MUSCLES OF A HUMAN HEART (RIGHT ATRIUM) X 240. The muscle fibrils in transverse sections appear as points; at i they are radially arranged.

In the heart of adult frogs, the system of intermuscular clefts or lacunar vessels is the only blood supply of the ventricular musculature; the coronary vessels are limited to the epicardium. In turtles the coronary vessels supply an outer layer of the ventricular muscles, but the greater part is still nourished by the central lacunae or sinusoids. This sinusoidal circulation, which is characteristic of the adult heart in lower vertebrates, occurs also in mammalian embryos, but it becomes vestigial in adult mammals.

A structure which has recently received much attention because of its functional importance is a small band of muscle fibers, associated with nerves, which passes from the septum between the atria into the septum between the ventricles. This atrio-ventricular bundle or "bundle of His"

(discovered independently in 1893 by Kent and His, Jr.) represents the only connection between the musculature of the atria and ventricles; it passes through the fibrous tissue where the annuli fibrosi come together. The position of the bundle is shown in Fig. 173, after Curran (Anat. Rec., 1909, vol. 3, pp. 618-632). Curran finds more extensive branches in the atria than others have shown. They come from both sides of the heart into the inter-atrial septum, and converge from the fossa ovalis, the roots of the tricuspid valve and the orifice of the coronary sinus to form the atrio-ventricular node. This is "a small mass of interwoven fibers in the central fibrous body of the heart, " and the main bundle, 2-3 mm. wide, passes from it into the inter-ventricular septum. It passes under the pars membranacea, and divides into two branches which are distributed to the right and left ventricles, respectively. Their extensive ramifications have been modelled by Miss DeWitt. She describes the models, and briefly summarizes previous investigations of the bundle, in the Anatomical Record (1909, vol. 3, pp. 475-497); the subject is more fully considered by Aschoff (Verh. d. deutsch. path. Gesellsch., 1910, PP- 3-35) The atrio-ventricular bundle is composed of muscle fibers which are pale macroscopically. They are larger than those of ordinary cardiac muscle, but contain fewer fibrils, peripherally placed and surrounded by abundant scaroplasm (Fig. 172). In the ventricle they are specially rich in glycogen. In the node, however, according to Miss DeWitt, the fibers, though varying greatly in size, are much smaller than those found elsewhere in the heart. Several of them unite at a point, producing stellate groups, and the entire node is an intricate network.

FIG. 173. THE ATRIO-VENTRICULAR BUNDLE (F. a. v.), AND THE POSITION OF THE "SlNO-ATRIAL NODE" (x) IN A HUMAN HEART. (After Curran and Aschoff.) Ao., Aorta; A. p., pulmonary artery; F. o., fossa ovalis; S. c., coronary sinus; R. d., right branch of the atrio-ventricular bundle; and R. s., its left branch; V. c. i. f vena cava inferior; V. c. s., vena cava superior.

The fibers of the atrio-ventricular bundle resemble those described by Purkinje in the sheep, horse, cow and pig, but which he could not find in the rabbit, dog and man (Arch. f. Anat., Physiol. u. wiss. Med., 1845, pp. 281-295). I n the walls of the ventricle, immediately beneath the endocardium, he observed "first with the naked eye, a network of gray, flat gelatinous threads, which in part were prolonged into the papillary muscles, and in part passed like bridges across the separate folds and clefts." Under the microscope, they appeared very granular, but he decided that they were probably muscular. Purkinje's fibers are regarded as imperfectly developed muscle fibers. In the human heart they are not as distinct from the other cardiac muscle fibers as in the sheep. It is possible that they are directly continuous with the cardiac syncytium, although, as noted by Miss DeWitt, if the transition is gradual it will be very difficult to observe in sections.

At the junction of the superior vena cava and the atrium, Keith and Flack have described a peculiar musculature imbedded in densely packed connective tissue, composed of striated, fusiform fibers, plexiform in arrangement, with .well-marked elongated nuclei, "in fact, of closely similar structure to the node" (Journ. Anat. and Physiol., 1907, vol. 41, pp. 172-189). These fibers are said to be in close relation with the vagus and sympathetic nerves; they have a special arterial supply. According to Keith and Flack they are situated at the junction of the sinus venosus and the atrium, and they form the sino-atrial node (sino-auricular node). The sino-atrial node is found immediately beneath the epicardium in the position shown in Fig. 173. In it the impulse for the heart beat is believed to originate, and to be transmitted to the atrio-ventricular node; the latter correlates the contraction of the atrium with that of the ventricle.

Epicardium. The epicardium is a connective tissue layer, covered with simple flat mesothelium and containing elastic fibers and many fat cells. The latter are distributed along the course of the blood vessels.

Vessels and Nerves. The branches of the coronary vessels pass from the epicardium into the myocardium, forming capillaries in intimate relation with the muscle fibers. The heart is thus supplied with aerated blood from the root of the aorta, as well as by the blood within its own cavities; on the left side this is aerated, but not on the right.

The lymphatic vessels, draining toward the base of the heart, are very abundant, and true lymphatic vessels are found in all layers of the heart. The tissue spaces in the myocardium are also extensive.

The nerves to the heart have already been described as forming the cardiac plexus. This plexus receives branches from the vagus, and from the sympathetic cardiac nerves proceeding from the cervical sympathetic ganglia. It sends its fibers toward the heart, where they follow the coronary vessels in their ramifications. The cardiac ganglion is associated with the superficial part of the cardiac plexus, and is under the arch of the aorta. Other small ganglia occur on the posterior wall of the atria, and scattered ganglion cells are found along the atrio-ventricular bundle. They have been reported along the nerves elsewhere in the heart. The ganglion cells are probably in connection with efferent fibers from the central nervous system, which include two sorts fibers from the ventral ramus of the accessory nerve, which pass out with the branches of the vagus and inhibit cardiac action; and fibers from the spinal nerves, by way of the inferior cervical ganglion, which accelerate it. Histologically nerve endings have been seen both within and around the capsules of cardiac ganglion cells. It is said that the medullated nerve fibers from the central system end within the capsules; and that nonmedullated branches from adjacent sympathetic ganglia end outside of them. Motor endings in contact with cardiac muscle have also been found. Sensory endings have been described both in the epicardium and endocardium. They consist of terminal ramifications forming "endplates." Some of these fibers presumably connect with sympathetic cells near at hand; others are terminations of afferent medullated fibers which are said to pass to the medulla, along the vagus trunk, as the "depressor nerve."

Lymphatic Vessels

General Features

The lymphatic vessels are far less conspicuous than the blood vessels, but they are no less important and are widely distributed throughout the body. Those which occur in the mesentery and are filled with a milky fluid after intestinal digestion has been going on, are the most conspicuous. These "arteries containing milk" were observed by Erasistratus, an anatomist of Alexandria who died in 280 B. C., but the observation was discredited by Galen. When Aselli in 1622 found the white vessels in a living dog which he had opened, and had shown by cutting into them that they were not nerves, it was essentially a new and great discovery. Aselli observed that the vessels were filled only after digestion, at other times being scarcely visible. He traced them to a mass of lymph glands which he mistook for the pancreas, and believed that they passed on into the liver (De lactibus sive lacteis venis, 1627). Years before the physiological observations of Aselli, Eustachius (who died in 1574) had described the main trunk of the lymphatic system in his treatise on the azygos vein (De vena sine pan, Syngramma XIII, Opusc. anat., 1707). He states that from the posterior side of the root of the left jugular vein (Fig. 174) "a certain large branch is given off, which has a semicircular valve at its origin, and moreover is white and full of aqueous humor."

" Not far from its source, it splits into two parts which come together a little further on. Giving off no branches, and lying against the left side of the vertebrae, having penetrated the diaphragm, it is borne along to the middle of the loins. There, having become larger and folded around the great artery, it has an obscure ending, not clearly made out by me up to the present time."

The vessel so well described by Eustachius is now known as the thoracic duct. It has the structure of a vein, and empties its contents into the blood at the junction of the left internal jugular and left subclavian veins. It receives branches from the left side of the head and the left arm, as well as from the trunk of the body. There is a corresponding vessel on the right side, known as the right lymphatic duct. It drains the right side of the head, the right arm, and adjacent territory, emptying at the junction of the right internal jugular and subclavian veins. Having no connection with the abdominal lymphatic vessels, however, it is much smaller than the thoracic duct on the left.

The connection between the lacteal vessels in the mesentery, seen by Aselli, and the thoracic duct observed by Eustachius, was demonstrated physiologically by Pecquet (Experimenta nova anatomica, 1651). He found a whitish fluid coming from the vena cava superior of a dog from which the heart had been excised, and observed that its flow was increased by pressure on the mesenteries. Moreover he described the receptaculum chyli, or enlargement of the thoracic duct dorsal to the aorta, which receives the chylous fluid. This is now called the cisterna chyli. The distribution, of the lymphatic vessels, which are ramifications of these main trunks, was followed out by skillful injections, and the results of such studies were presented in great folios by Mascagni (1787) and Sappey (1874). Considered as a whole the lymphatic system may be compared with a venous system which has no corresponding arteries; it is composed entirely of afferent vessels.

Recent anatomical studies of these vessels have been concerned with their origin, and their relation in the adult to the surrounding connective tissue. The vessels have long been known as absorbents, and it was thought that they opened freely at their distal ends into the connective tissue spaces; through these openings they were supposed to suck in the tissue fluid which had escaped from the vessels, and the chylous fluid, charged with nutriment, which had entered the intestinal tissues, and to convey this material back to the blood vessels. Thus the lymphatic vessels were described as tissue spaces, which had elongated and coalesced so as to form tubes bounded by flattened connective tissue cells, and these vessels were thought subsequently to acquire openings into the veins. Opposed to this conception is the idea of Ranvier that the lymphatic vessels are primarily connected with the veins. They grow out from the veins as endothelial sprouts, which form a closed system of endothelial tubes, anastomosing freely with one another, but never with the blood vessels. Thus they are connected with the veins by main trunks comparable with the ducts of glands (Arch. d'Anat. micr., 1897, vol. i, pp. 69-81). Fluids may pass through the thin endothelium almost as readily as through open orifices, so that functionally the distinction does not appear to be fundamental.


Ranvier's interpretation has been defended by MacCallum, on the basis of histological studies (Arch. f. Anat. u. Physiol., Anat. Abth., 1902, pp. 273-291), and by Miss Sabin, from the injection of the lymphatic vessels in embryos (Amer. Journ. Anat., 1902, vol. i, pp. 367-389). The most convincing evidence in its favor has been supplied by Clark's observations on the growth of the lymphatic vessels in the tails of tadpoles. The tadpoles were anaesthetized with chloretone. The membranous part of the tail was then examined with immersion lenses, and certain of the lymphatic vessels were drawn. The animals were restored to normal condition and were re-examined at intervals of twelve hours. The growth of a given lymphatic vessel was thus demonstrated, as shown in Fig. 175. Its elongation and enlargement were seen to be independent of the surrounding connective tissue, through which it made its way.

FIG. 175- SUCCESSIVE STAGES IN THE GROWTH OF A LYMPHATIC VESSEL (lym.) IN THE TAIL OF A TADPOLE (Rana paluslris). Xi35- (Clark.) b. v., Blood vessel; n., nucleus of the lymphatic vessel.

In some cases a blood corpuscle had escaped into the intercellular spaces. Toward such a corpuscle the lymphatic vessel grew, and having reached it, the corpuscle was taken in by the endothelial cells and transferred to the lumen of the vessel, through which it was seen to travel toward the central vessels. As indicated in Fig. 175, the nuclei of the living endothelium could be observed, and the multiplication of the endo thelial cells during the growth of the lymphatic vessel was demonstrated (Anat. Rec., 1909, vol. 3, pp. 183-198).


The development of the mammalian lymphatic system begins with the formation of a pair of very large sacs lined with endothelium, situated at the junction of the jugular and subclavian veins (Fig. 176). These jugular lymph sacs were first described by Miss Sabin (loc. cit.}\ they appear in human embryos measuring about 10 mm. and are formed by the union of several outgrowths from the veins. In slightly older embryos, another lymph sac is produced at the root of the mesentery, below the place where the renal veins enter the vena cava inferior (Lewis, Amer. Journ. Anat., 1920, vol. i, pp. 220-244). The opinion that this sac is a derivative of the adjacent veins has been confirmed by certain later embryological studies, and by finding permanent communications between the lymphatic and the venous system at the level of the renal veins in adult The lymphatics are heavily shaded, x being a vessel along the left


South American monkeys (Silvester, Amer. Journ. Anat., 1912, vol. 12, pp. 446-460). At other places, which must be regarded as secondary centers, lymphatic vessels appear to be derived from the veins and to become detached from them. These vessels are seen in the mesenchyma as isolated spaces, usually along the course of the veins, at no great distance from the jugular and mesenteric lymphatics. Subsequently they become connected with one another by endothelial outgrowths, such as extend from the lymphatic vessels into the peripheral tissues as described by Clark. The mesenteric sac thus becomes connected with the left jugular sac (symmetrical connections with both jugular sacs occur in some animals) and the connecting vessels constitute the thoracic duct. The cisterna chyli is a secondary enlargement dorsal to the aorta. In the adult the sacs are replaced by plexuses of smaller vessels.

vagus nerve and y along the aorta. The large jugular lymph sac is in contact with the internal jugular vein. In J.; it passes to the junction of the external jugular (Ex. J.) and subclavian veins, the latter being formed by the union of the primitive ulnar, Pr. Ul., and external mammary veins, Ex. M. The mesenteric sac is in front of the vena cava inferior (V. C. I.) and below the renal anastomosis (R. A.). Other veins include Az., azygos; V., vitelline; G., gastric; S. M., superior mesenteric; etc. The figures indicate the position of the corresponding cervical nerves.

The origin of the detached or apparently detached lymphatic spaces in embryos, which precede the formation of the well-defined vessels, has been studied with great diligence by Huntington (The Anatomy and Development of the Lymphatic System, Mem. Wistar Institute, 1911) and McClure (Anat. Rec., 1912, vol. 6, pp. 233-248), to whose many contributions references will be found in the papers cited. They consider that the lymphatic spaces arise in large part as mesenchymal spaces, but the possibility suggested by Bremer's recent work on the blood vessels, that uninjectable endothelial strands of great delicacy may pass to these cavities, has not been set aside, and further work upon this subject is being conducted under Professor McClure's direction. The reasons which led the writer to consider the origin of the lymphatic vessels from mesenchymal spaces as improbable, were stated as follows (Amer. Journ. Anat, 1905, vol. 5, pp. 95-120).


a, d., Lymphatic vessels; b, vein; c, artery.

" i. The lymphatic spaces do not resemble mesenchyma even when it is oedematous, but on the contrary, are scarcely distinguishable from blood vessels (Langer)."

" 2. After being formed, the lymphatics increase like blood vessels, by means of blind endothelial sprouts, and not by connecting with intercellular spaces (Langer, Ranvier, MacCallum, Sabin)." The subsequent work of Clark is here conclusive.

"3. In early embryos detached blood vessels may be seen without proving that blood vessels are mesenchymal spaces. These detached vessels are not far from the main trunks, from which they may have arisen by slender endothelial strands, yet often the connecting strands cannot be demonstrated." (Subsequently, Bremer demonstrated such strands in great abundance.)


"4. The endothelium of the embryonic lymphatics is sometimes seen to be continuous with that of the veins" i.e., in certain places, as in connection with the jugular sac, the origin of the lymphatic vessels from the venous endothelium can be clearly seen; this fact is conclusively demonstrated by Huntington and McClure, who use the term " veno-lymphatic " for transitional vessels (Amer. Journ. Anat., 1910, vol. 10, pp. 177-311).

Lymphatic Vessels in the Adult

In sections of the intestine from an animal in which intestinal digestion was in progress, lymphatic vessels may readily be found between the muscle layers (Fig. 177). Their walls are decidedly thinner than those of blood vessels of the same caliber, and their contents are typically a granular or fibrinous coagulum free from red corpuscles, but containing an occasional lymphocyte. It must be remembered, however, that blood vessels seen in sections are not infrequently empty, and that blood corpuscles may be taken into the lymphatic vessels. Having learned to recognize the lymphatics in such favorable situations as the intermuscular tissue, one may readily identify them in the connective tissue layer internal to the circular muscle of the intestine, and in the connective tissue around the bronchioles in the lung; in the embryonic lung they are very conspicuous. They may then be sought for in various organs, but a sharp distinction must be drawn between the endotheliumlined lymphatic vessels and the interfibrillar tissue spaces. When prepared with silver nitrate, the outlines of the endo thelial cells are seen to resemble those of blood vessels (Fig. 178), and in the larger lymphatic vessels the endothelium with the underlying connective tissue forms a tunica intima. These lymphatics (0.2-0.8 mm. in diameter), are often composed of three coats, though loose in texture. The media contains circular smooth muscle fibers and a small amount of elastic tissue; and the externa is composed of longitudinal connective tissue and scattered bundles of longitudinal muscle. Thus they resemble the veins more closely than the arteries. Valves are very numerous in lymphatic^ vessels^ They are shown in section in Fig. 179. In the small vessels the valves are described as folds of endothelium, such as would be produced if the distal part of the vessel were pushed forward into the proximal part. The vessels are often distended on the proximal side of the valve, producing bulbous enlargements, as shown in Fig. 178. Owing to the presence of these valves, compression of tissue containing lymphatic vessels, or the contraction of the muscles of the media, causes an onward flow of the lymph. The nerves to lymphatic vessels are like those of the blood vessels. Lymphatics are provided with vasa vasorum. As shown by Evans (Amer. Journ. Anat., 1907, vol. 7, pp. 195-208) very small lymphatic vessels are accompanied by blood capillaries, and the larger lymphatics are surrounded by a wide-meshed capillary network resting on the outer side of the lymphatic media. (In the same volume of the Journal, pp. 389-407, Miller describes the network of blood capillaries around the lymphatic vessels of the pleura.)

FIG. 179.

Lymphatic vessel from a section of a human bronchus, showing a valve, v. ; distal to the branch, br. Bundles of smooth muscle fibers are seen at m. f.


Blood consists of round cells entirely separate from one another, floating in an intercellular fluid, the plasma. The plasma also contains as a regular and apparently important functional constituent, the blood plates (or platelets), together with smaller granular bodies. Blood cells or corpuscles are of two sorts, (i) red corpuscles or erythrocytes, which become charged with the chemical compound, hcemoglobin, and which lose their nuclei as they become mature; and (2) white corpuscles or leucocytes, which are of several kinds, all of them retaining their nuclei and containing no haemoglobin. The redness of blood is not due to the plasma, but is an optical effect produced by superimposed layers of the haemoglobin-filled red corpuscles. Thin films of blood, like the individual red corpuscles seen fresh under the microscope, are yellowish green. Blood has a characteristic odor which has been ascribed to volatile fatty acids; it has an oily feeling associated with its viscosity, an alkaline reaction, and a specific gravity said to average in the adult from 1.050 to 1.060.


Development. The first cells in the embryonic blood are apparently all of one sort, derived from the blood islands. They are large, round cells with a delicate membrane and a pale granular protoplasmic reticulum; their relatively large nuclei contain a fine chromatin network with several coarse chromatin masses. Haemoglobin later develops in their protoplasm, giving it a refractive homogeneous appearance. Stained with orange G or eosin it is clear and brightly colored, generally quite unlike any other portion of the specimen. Often the haemoglobin has been more or less dissolved from the corpuscles, which then appear granular or reticular.

The developing red blood corpuscles are known as erythroblasts, especially in their younger stages when the nuclei are reticular. In later stages the nuclei become densely shrunken or pycnotic, and stain intensely with haematoxylin. The entire cells become smaller, and are then called normoblasts. The transition from an erythroblast to a normoblast is shown in Fig. 180, a; during this process the cells divide repeatedly by mitosis.

It will be noticed that the terms applied to developing corpuscles are compounded of words which describe the formative cells, instead of indicating what they produce. Thus erythroblast signifies a red formative cell. Normoblast (Lat. norma, model or type, and Gr. ^Xcwrtfy) is an objectionable term to designate a nucleated red corpuscle of the usual size and form, in contrast with the large megaloblasts which occur in certain diseases of the blood. Megaloblasts have reticular nuclei and presumably represent a younger stage than the normoblasts. A reform in the nomenclature of blood cells based upon morphological principles, is advocated by Minot (Human Embryology, ed. by Keibel and Mall, 1912, vol. 2), and when agreement shall have been reached regarding the relationships of the cells, it will be possible to adopt a reasonable terminology.

In becoming mature red corpuscles the normoblasts lose their nuclei. Before they disappear, the pycnotic nuclei often assume mulberry, dumbbell, trefoil or other irregular shapes. According to older observations they then fragment, and are dissolved within the normoblasts; but it is now generally believed that they are extruded from the cells, either in one mass (Fig. 180, b) or in detached portions, and that the extruded nuclei are devoured by phagocytes. The loss of the nuclei begins in human embryos of the second month. In embryos of the seventh month, nucleated corpuscles

in the circulating blood have become infrequent, and after birth it is rare to find one, except under pathological conditions.

In withdrawing from the circulating blood the nucleated red corpuscles do not disappear from the body. Since 1868 it has been known that the red marrow, found within certain bones in the adult, contains an abundance of erythroblasts, which multiply by mitosis. They are the source of the new corpuscles constantly entering the circulation. In certain diseases of the blood, imperfectly developed normoblasts also leave the marrow, and circulate as in the embryo. Before the marrow assumes the bloodforming function, the liver is the chief haematopoietic organ. Beginning in embryos of about 7.5 mm., and continuing until birth, erythroblasts are found between the hepatic cells and the endothelial cells of the sinusoids, and in certain stages they occur in vast numbers. Toward birth,



(Howell.) a, Successive stages in the development

of a normoblast; b, the extrusion of

the nucleus.

i go


however, the erythroblasts in the liver are no longer abundant, and in a few weeks after birth they are said to disappear entirely. Red blood corpuscles are formed also in the embryonic spleen, though to a less extent than in the liver, and in some mammals the spleen normally

contains erythroblasts in the adult. In regard to the source of the erythroblasts in the spleen, liver and red marrow, two opinions are held. It is well known that erythroblasts and fully-formed red corpuscles may wander out of the vessels into connective tissue. Accordingly it is often stated that the circulating erythroblasts, which at first multiply in the blood vessels, later withdraw to the reticular tissue of the liver, spleen, and

marrow and there proliferate. Others consider that the erythroblasts are formed in situ in these various places from the endothelial or reticular tissue cells.

Mature Red Corpuscles. In the lower vertebrates, !the mature red

Leucocyte in motion; at rest.

Side view of red corpuscles.


4, 5, and 6, Surface views of red corpuscles; 6, after

treatment with water. X 600.


corpuscles or erythrocytes are oval nucleated bodies, more or less biconvex, thus differing radically from those of adult mammals. They are very large in the amphibia (Fig. 181). When a drop of freshly drawn mammalian blood is spread in a thin film on a glass slide, beneath a cover


glass, it is seen to consist chiefly of biconcave discs, and of those in the form of shallow saucers (Fig. 182). They have a remarkable tendency to pile up in rouleaux, like rolls of coins. It is said that discs of cork weighted so that they will float beneath the surface of water, will come together in a similar way if their surfaces have been coated with an oily substance. If the blood coagulates, filaments of fibrin will be seen in the plasma, as shown in the figure. In fresh specimens there is no fibrin, and within the blood vessels it does not form under normal conditions. Moreover when they are within the endothelial tubes, red corpuscles do not come together in rouleaux. It is evident that the thin film of blood, though very fresh, is examined under extremely artificial conditions; and from such preparations, conclusions as to the normal shape of the corpuscles should not be hastily drawn. Within the blood vessels the red corpuscles are typically cup-shaped.

Rindfleisch (Arch. f. mikr. Anat., 1880, vol. 17, pp. 21-42) found that the corpuscles in guinea-pig embryos, after losing their nuclei by extrusion, are at first bell-shaped; but he considered that afterward they become biconcave discs from impact with others in the circulating blood. Commenting upon this statement, Howell (Journ. of Morph., 1890, vol. 4, pp. 57-116) writes:

"I feel convinced that the bell shape which Rindfleisch ascribes to the corpuscles which have just lost their nuclei is a mistake. The red corpuscles even of the circulation, as is well known, frequently take this shape when treated with reagents of any kind, or even when examined without the addition of any liquid. It seems very natural to suppose that the biconcavity of the mammalian corpuscle is directly caused by the loss of the nucleus from its interior. Certainly as long as the corpuscles retain their nuclei, they are more or less spherical, and after they lose their nuclei they become biconcave."

In the year preceding Howell's publication, Dekhuyzen discussed cup-shaped corpuscles (Becherformige rote Blutkorperchen, Anat. Anz., 1899, vol. 15, pp. 206-212) which he found as a transient stage in mammals, and which his assistant saw in blood drawn from his finger. Dujardin (Manuel de 1'observateur au microscope, 1842) found many corpuscles shaped "like cups, or cupules (acorn cups) with thick borders" in blood altered by the action of phosphate of soda. The first reference to such forms is by Leeuwenhoek (1717) who put a drop of blood in a concoction of pareira brava, and found that most of the globules which make the blood red, have "a certain bend or sinus receding within, as if we had a vesicle full of water and by pressure of the finger should hollow out the middle of the vesicle as a pit or depression." Von Ebner, in Koelliker's Handbuch (1902), writes of bell or cap-shaped corpuscles produced in warmed blood by the thickening of the border on one surface of the disc. Weidenreich in 1902 (Arch. f. mikr. Anat.. vol. 61, pp. 459-507) after thorough study of blood variously preserved, and also examined while circulating in the mesentery of a rabbit, concluded that "the red corpuscles of mammals have the form of bells (Glocken)." Weidenreich's conclusion has not been fully accepted by Jolly, David, Jordan, and Schafer. Schafer (in Quain's Anat., vol. 2, 1912) states that " this opinion, although shared by F. T. Lewis, Radasch and a few other histologists, cannot be accepted, for, of examining the circulating blood in the mesentery and other transparent parts in mammals, it is easy to observe that, with few exceptions, the erythrocytes are biconcave; this shape must therefore be regarded as the normal one."


That the shape of corpuscles in the circulating blood is not easy to observe, is shown by the fact that scientists have described it in very different ways. The circulating corpuscles may be seen by spreading the mesentery of an anaesthetized guinea-pig across the condenser of a microscope, having it' preferably in a warm room, and then placing a cover glass directly over the vessels; they are examined with an immersion lens. Sketches made during such observations are reproduced in Fig. 183. The upper drawing shows a vessel stretched out abnormally, and the corpuscles are correspondingly elongated; the one at the left shows the hollow of the cup toward the observer, the others are seen in lateral view. Presumably normal conditions are shown in the lower sketch, which includes two flat corpuscles, one of which is almost biconcave, but this form is exceptional. The corpuscles are very flexible, bending around any obstruction, and when free, again assuming their original form. They roll about as they flow through the vessels, and when, FIG. 183. RED CORPUSCLES, SKETCHED as the blood stagnates, the current in the vessels


SELS OF THE OMENTUM OF A GUINEA- is sometimes reversed, their form does not change.

In 1903, following Weidenreich's publication, the

writer demonstrated the circulating corpuscles to Professor Minot, who describes the cup-shape as the normal form in Keibel and Mall's "Embryology"; and in 1909 they were shown to Dr. Williams who was convinced that they are cup-shaped.

A very important result of recent studies (which Schafer does not mention) is the recognition that in well preserved tissues of all sorts, and with all fixatives such as are relied upon to reveal the structure of other tissues, the mammalian erythrocytes are typically cup-shaped. Other forms are exceptional. In many specimens the corpuscles and other tissues are irregularly shrunken, but where the tissues in general are excellently preserved, the corpuscles appear as cups. The biconcave discs are flattened cups.

In examining films of fresh blood, the biconcave discs will be seen to change their appearance as the objective is lowered. When sharply in focus the thin central portion appears light (Fig. 184, A); but in high focus the center is dark, perhaps owing to the dispersal of light by the lenticular corpuscles. The biconcave shape is apparent when the corpuscle is seen on edge (Fig. 184, B). The cup-shaped forms are shown in Fig. 184, D; and E represents one of the innumerable shapes due to shrinkage. The cups may be irregularly infolded, presenting shapes which can be imitated by indenting a soft hat. If the corpuscles are placed in water or a dilute solution, their haemoglobin passes out and water enters, so that they are reduced to transparent membranes or shadows (Fig. 184, F). Such forms are often seen in clinical examinations of urine. In dense solutions, and in fresh preparations as the plasma becomes thicker from evaporation, water leaves the corpuscles. They then shrink, producing spiny or nodular round masses of haemoglobin, known as crenated corpuscles (Fig. 184, G). A 0.6 per cent, aqueous solution of common salt is said to cause the least distortion from swelling or shrinkage. In life the corpuscles doubtless change their shape, responding to the


variations in their haemoglobin content and in, the surrounding plasma. Occasionally they are spherical (according to Schultze, and others), and deviations from the primary cup-shaped form are to be expected. In these changes the corpuscles act like membranes filled with fluid. In the mature corpuscles, however, the outer layer is thick, blending with the contents within; and since no sharp bounding line can be seen histologically, the corpuscles have been described as lacking membranes. The plastic nature of the membrane is shown by heating the blood film. The corpuscles then become globular and send out slender varicose processes, or round knobs attached by pedicles (Fig. 184, H). These small spheres become detached in great numbers.

The dimensions of red corpuscles are quite constant. Those in human blood average 7.5 n in diameter and ordinarily vary from 7.2 to 7.8 /*. They sometimes surpass these limits. In biconcave form they are about 1.6 n thick. The cups average 7 ju in diameter and are 4 n in depth.


Spherical corpuscles are said to be 5 n in diameter. The blood of mammals other than man also contains cups which become discs. The latter are oval in the camel group but round in all others. Their average diameters are less than in man (7.3 ju in the dog, 7.48 n in the guinea-pig), but the species of animal cannot satisfactorily be determined from the diameter of the corpuscles. In a given section, as already noted, the red corpuscles furnish a useful gauge for estimating the size of other structures.

The number of red corpuscles in a cubic millimeter of human blood averages five million for men, and four million five hundred thousand for women. By diluting a small measured quantity of blood and spreading it over a specially ruled slide, the corpuscles may be counted, and the number per cubic millimeter calculated. A diminished number is of clinical importance.

Histologically the red corpuscles usually appear as homogeneous bodies, but with special methods a granular network has been found within them, which has been interpreted as a reaction of the haemoglobin to reagents, and also as a persistence of the protoplasmic reticulum of the erythroblasts. It occurs especially in newly formed corpuscles (seen in cases of anaemia). Instead of a net, there may be rings or round 13


bodies, some of which have been considered to be nuclear remains. A few coarse granules of uncertain significance are sometimes conspicuous. The fatty exoplasmic layer which invests the corpuscle and serves as a membrane is not sharply marked out in stained specimens; it appears to blend with the contents of the corpuscle. Although the corpuscles may pass out of the vessels by " diapedesis," they are not actively motile, and their margins never present pseudopodia. The characteristics of haemoglobin may be described as follows:

Haemoglobin is an exceedingly complex chemical substance which combines readily with oxygen to form oxyhamoglobin. To the latter the bright color of arterial blood is due. Venous blood becomes similarly red on exposure to air. Through the oxyhaemoglobin, oxygen is transferred from the lungs to the tissues. Haemoglobin may be dissolved from the corpuscles by mixing blood with ether, and upon evaporation it crystallizes in rhombic shapes which vary with different animals. Those from the dog are shown in Fig. 185, 4; in man they are also chiefly prismatic. Haemoglobin is readily


FIG. 1 8s- 1 Haemin crystals and 3, haematoidin crystals from human blood; a, crystals of common salt (X 560); 4, haemoglobin crystals from a dog (X 100).

decomposed into a variety of substances, some of which retain the iron which is a part of the haemoglobin molecule, others lose it. Hcsmatoidin, considered identical with a pigment (bilirubin) of the bile, is an iron-free substance occurring either as yellow or brown granules, or as rhombic crystals. The crystals (Fig. 185, 3) may be found in old blood extravasations within the body, as in the corpus luteum of the ovary. Hcemosiderin, which contains iron, appears as yellowish or brown granules sometimes extremely fine, either within or between cells. The iron may be recognized by the ferrocyanide test which makes these minute granules bright blue. If dry blood from a stain is placed on a slide with a crystal of common salt the size of a pin-head, and both are dissolved in a large drop of glacial acetic acid which is then heated to the boiling point, a product of haemoglobin is formed, called hamin. It crystallizes in rhombic plates or prisms of mahogany brown color (Fig. 185, i). Such crystals would show that a suspected stain was a blood stain, but they afford no indication of the species of animal from which it was derived.

The duration of the life of mature red corpuscles is unknown, but is supposed to be brief. They may be devoured intact by phagocytes, but generally they first break into numerous small granules. These may be ingested by certain leucocytes, or by the peculiar endothelial cells of the liver. Their products are thought to be eliminated in part as bile pigment. The destruction of red corpuscles occurs especially in the spleen and haemolymph glands; to a less extent in the lymph glands and red bone marrow. Pigmented cells in some of these structures derive their pigment from destroyed corpuscles. Sometimes a 'stippling' or granule formation occurs within the corpuscle, which has been ascribed to degeneration of the haemoglobin. The dissolution of red corpuscles is known as hamolysis and follows the injection of certain poisonous substances into the blood. It occurs in various diseases. The study of the effects of mixing the blood of one species of animal with that of another, has provided a very perfect means of distinguishing the species from which a blood stain of unknown origin may have been derived.

WHITE CORPUSCLES. The white corpuscles or leucocytes are thoset blood cells which retain their nuclei and do not contain haemoglobin.! The youngest stages of erythroblasts, according to this definition, are leucocytes, and like other leucocytes they are derived from the mesoderm. In 1890 Howell wrote, "Before 1869 it was quite generally believed that the red corpuscles are formed from the white corpuscles in fact, some of the most recent investigations favor this view, although the evidence is so overwhelmingly against it." It is still advocated by foremost investigators of the blood, and is referred to as the " monophyletic theory." Those who believe in diverse origins of red and white corpuscles, and of the various forms of white corpuscles, support the "polyphyletic theory."

Maximow (Arch. f. mikr. Anat., 1909, vol. 73, pp. 444-561) states that "the first leucocytes, the lymphocytes, arise at the same time and from the same source as the primitive erythroblasts; the latter represent a specially differentiated form of cell, but the lymphocytes always remain undifferentiated. Therefore, like the primitive blood cells from which they directly proceed, they are undifferentiated rounded amoeboid mesenchymal cells." Weidenreich (Anat. Rec., 1910, vol. 4, pp. 317-340) concludes that "the old, original view of the unified genetic character of all blood cells proves to be correct," and he regards the lymphocyte as the primitive or young form of white corpuscles. (For many other references, see Minot, in Keibel and Mall's Human Embryology, vol. 2.)

Against the monophyletic interpretation, it has been asserted that the lymphocytes of the adult are a different form of cell from the primitive blood cells, and that they are not found in embryos until the time when lymph glands develop. These arise rather late in rabbits of 25 mm. and in human embryos of 40 mm. (Lewis, Anat. Rec., 1909, vol. 3, pp. 341-353). According to the polyphyletic view, the lymphocytes are first formed from the reticular tissue in these glands and from similar tissue elsewhere. If this is true, it becomes unnecessary to regard the lymph glands as organs for producing young cells, and the bone marrow as an organ for producing old cells. The relation of these organs to blood formation will be considered in a later chapter.

The number of white corpuscles in a cubic millimeter of human blood is about eight thousand. If it exceeds ten thousand the condition is called leucocytosis and becomes of clinical importance. There exists, therefore, normally but one leucocyte for five or six hundred red corpuscles. In the circulating blood the two sorts are said not to be evenly mixed; the leucocytes are more numerous in the slower peripheral part of the blood stream, near the endothelium. The leucocytes may be divided into three classes according to their nuclear characteristics, namely, into lymphocytes, large mononuclear leucocytes, and polymorphonuclear leucocytes.

Lymphocytes have already been briefly described with the constituents of connective tissue (Fig. 56, p. 68). Ordinarily they are small cells, about the size of red corpuscles, 4-7.5 M in diameter. Large ones may be double this diameter. Their protoplasm forms a narrow rim, sometimes almost imperceptible, about the dense round nucleus (Fig. 186, A). The chromatin is arranged in a network associated with coarse chromatic masses such as cause a characteristic checkered appearance. Some of the masses rest against the nuclear membrane. Lymphocytes are capable of amoeboid motion but not to the extent of the poly

FIG. 186. LEUCOCYTES AS SEEN IN A SECTION OF Hu mOrphonUClear type. They


A, Lymphocyte; B, large mononuclear leucocyte; C, form trom 22 tO 25% OI all

three polymorphonuclear neutrophiles. ,


Large mononuclear leucocytes, sometimes 20 M in diameter, form only from i to 3% of the leucocytes. They possess round, oval, slightly indented, or crescentic nuclei, which are vesicular and usually eccentric in position. Their chromatin occurs in a few large granules; as a whole the nucleus is clear and pale (Fig. 186, B). The protoplasm, which is abundant, usually lacks coarse granules or other distinctive features. Sometimes it contains a few deeply staining granules as shown in one of the cells in Fig. 187, II. The large mononuclear leucocytes are notably phagocytic. In certain respects they are intermediate between lymphocytes and polymorphonuclear cells, and they were formerly known as "transitional cells." Apparently, however, they are derived directly from the modified endothelial cells lining the sinuses of the lymph glands, and they have sometimes been regarded as the youngest of the forms of cells shown in Fig. 186.

Polymorphonuclear leucocytes are cells somewhat larger than red corpuscles, being from 7.5 to 10 /* in diameter. They are characterized by having nuclei with irregular constrictions leading to an endless variety of shapes (Fig. 186, C). The nodular subdivisions may be connected by broad bands or by slender filaments. It is said that in degenerating cells the nucleus becomes divided into several separate masses. Such forms can properly be called "polynuclear," an abbreviated term which is a misnomer as applied to the ordinary cells; "mononuclear" as designating the preceding types is also unfortunate since it implies that others have several nuclei. The irregular shape of the polymorphous nuclei has been ascribed to degenerative changes, comparable to those seen in the erythroblast nuclei. Within the concavity of the nucleus the centrosome may be found, surrounded by a light area; usually it occurs as a diplosome.

(In the forms of corpuscles with round nuclei eccentrically placed, the centrosome is on the side where the protoplasm is most abundant.) The polymorphonuclear leucocytes are actively amoeboid, and particles readily pass through their superficial layer, but like other forms of leucocytes they are covered with a very delicate cell membrane.

Max Schultze in the first paper published in the Archiv fur mikroskopische Anatomic (1865, vol. i, pp. 1-42) described an apparatus for the examination of microscopic specimens at the body temperature, which he used in studying human blood. He observed the active creeping movements of the leucocytes, closely similar to those of the most delicate amoebae, and watched them take up particles of carmine and other dyes placed in a drop of fresh blood. "The act of ingestion," as he describes it, "is accompanied by no striking maneuver." He adds that he has never seen special processes sent out to overcome foreign bodies, but that the creeping corpuscle, during its uniform advance, passes over them and presses them into its substance. He diluted the blood with two-thirds of its volume of fresh cow's milk, and observed that the leucocytes moved with the same rapidity as before, and ingested the oil globules which are much larger than the pulverized dye-stuff.

A fundamental characteristic of polymorphonuclear leucocytes is the j development of distinct granules in their protoplasm. They can be seen in fresh unstained specimens, in which it is evident that some of the cells contain coarse granules, and others fine granules. The lymphocytes and the large mononuclear leucocytes contain neither sort, and are therefore described as non-granular. In order to study the granules a drop of blood is spread thinly over a cover glass and dried, afterward being stained with a "blood stain," which is a carefully prepared mixture of acid and basic dyes. The details of nuclear structure are not preserved by this method, but the granules are clearly differentiated (Fig. 187). With several of the blood stains the fine granules are colored purple or lilac; and the coarse granules are found to be of two sorts, one kind staining red with eosin, and the other blue with the basic dye. Only one sort of granule occurs in a single cell.

Leucocytes containing coarse blue granules, which often obscure the nucleus, are called mast cells. In order to distinguish between them and the mast cells of connective tissue, which contain similar granules (see Fig- 55> P- 68) those in the blood are often called mast leucocytes. They form only 0.5% of the leucocytes, and in sections special methods are required to demonstrate them. These cells have recently been interpreted as degenerating forms, but their significance has not been fully established.

Leucocytes with coarse granules which stain red with eosin, an acid stain, are called eosinophiles (sometimes oxyphiles, or acidophiles). They constitute from 2 to 4% of the leucocytes in the blood. Eosinophilic cells, apparently distinct from those of the blood, occur also in connective tissue, and since their granules are preserved by ordinary methods, and eosin is a dye used in routine examinations, these cells are often seen. According to Weidenreich the eosinophilic granules are minute fragments of red corpuscles, or products of their degeneration, which have been ingested. Badertscher (Amer. Journ. Anat., 1913, vol. 15, pp. 69-86) finds that eosinophiles are very numerous in the vicinity of the degenerating muscle fibers in salamanders, during the time when their gills atrophy. He agrees with Weidenreich that the eosinophilic granules are not products of protoplasmic activity but are derived from material outside of the cells; and he likewise finds that they are taken up by lymphocytes which thus become eosinophiles. Badertscher's work is of interest in connection with cases of trichiniasis in man, in which the number of eosinophiles in the blood becomes greatly increased, and at the same time there is extensive degeneration of the muscles, caused by the parasites. There is, therefore, reason to believe that esinophilic granules are haemoglobin derivatives, but, as stated by Minot, "renewed investigation of the eosinophiles in man is very desirable."

FIG. 187. THE BLOOD CORPUSCLES. (WRIGHT'S STAIN.) (E. F. Faber, from Da Costa's Clinical Hsematology.)

I, Red corpuscles, n, Lymphocytes and large mononuclear leucocytes, m, Neutrophiles. IV, Eosinophiles. V, Myelocytes (not found in normal blood). VI, Mast cells.

The third type of granular cell, unlike the eosinophiles and mast cells, contains fine granules, and these stain purple or lilac by taking both acid and basic stains simultaneously. They are called neutrophiles, and form between 70 and 72% of the leucocytes in the blood. They are actively amoeboid and are the principal wandering cells of the body, leaving the blood vessels more readily than other forms. In suppurative processes they accumulate around the centers of infection, and they are of very great clinical importance.


Lymphocytes, 22 to 25% of the leucocytes, are small (about the. size of a red corpuscle) or large (perhaps twice the diameter of a red corpuscle), non-granular, with round checkered nuclei.

Large mononuclear leucocytes, i to 3%, may be two or three times the diameter of red corpuscles. They are non-granular, or with few granules, and have pale vesicular nuclei, round or crescentic.

Polymorphonuclear leucocytes, larger than red corpuscles, are granular, with nuclei variously constricted or bent. They include

Mast cells, 0.5%, with very coarse basophilic granules obscuring

the nucleus.

Eosinophiles, 2 to 4%, with coarse eosinophilic granules. Neutrophiles, 70 to 72%, with fine neutrophilic granules. Blood plates (Fig. 188) are small granular bodies (Kb'rnchenplaques) which were recognized as a normal constituent of the blood by Schultze in 1865. Previous references to them occur, and Zimmermann described them as "elementary corpuscles," believing that they gave rise to red corpuscles (Arch. f. path. Anat., 1860, vol. 18, pp. 221-242). They are 2-4 n in diameter, and between 245,000 and 778,000 have been estimated to occur in a cubic millimeter of human blood.

They are readily reduced to granular debris in ordinary


sections, but when well preserved and properly stained, they are found to consist of a central granular core and a hyaline outer layer. Often they appear stellate, and on a warm stage they exhibit amoeboid movements. They are concerned in the clotting of the blood, or thrombus formation, and during coagulation threads of fibrin extend out from them as seen in Fig. 182. It is possible, however, that they are only passively involved in this process. In the amphibia certain small spindle-shaped cells appear to be similarly related to fibrin-formation, and they are called thrombocytes; the same term is sometimes applied to the blood plates. In blood clots several days old, blood plates are still found, indicating that they have more than a transient existence.


The source of the blood plates has been known to American histologists for several years, since they have had the opportunity of examining preparations made by J. H. Wright and described by him in 1906. The specimen shown in Fig. 189 is one of several which were entrusted to the writer for demonstration at the meeting of the American Association of Anatomists in 1906; figures of them are reproduced in color in the Journal of Morphology (1910, vol. 21, pp. 265-278). Fig. 189 represents a giant cell of the bone marrow, sending out two processes or pseudopodia into a blood vessel; the endothelium is interrupted at their place of entrance. By the special stain which Dr. Wright perfected, the central and large part of the cytoplasm of the giant cells is seen to consist of red or violet granules, identical in form and color with the granules in the center of the blood plates. Moreover the giant cells are shown to have a clear blue exoplasmic layer, which sends out slender processes, and this exoplasm also is identical in structure with that of the blood plates. Some of the blood plates are free in the vessels; others in rows or clumps are still connected with the giant cells. Fig. 189 shows a few detached plates, and one which is budding off from a pseudopodium, but the colorcontrasts which make these preparations convincing are scarcely indicated. Through Wright's investigations it has been made clear that blood plates are detached portions of the cytoplasm of the giant cells in the bone marrow, and of similar giant cells in the spleen; their granular center is endoplasm, and their hyaline border is exoplasm.


According to Schafer (1912) Wright's "suggestion" seems improbable; and the blood plates may be looked upon as minute cells. Others also have regarded the granular endoplasm as a nuclear structure. The blood plates are still described by many writers as fragments of disintegrating white corpuscles, or fragmenting nuclei of red corpuscles; and Stohr records that their origin is obscure.

Plasma is the fluid intercellular substance of the blood. It contains various granules, some of which are small fat drops received from the thoracic duct. Others occurring in variable quantity are refractive particles, not fatty, either round or elongated; they are known as haematoconia (or hsemoconia). In ordinary sections the plasma appears as a granular coagulum. In the process of clotting, fibrin forms from the plasma, and with the entangled corpuscles, it constitutes the blood-clot; the fluid which remains is the serum. The process of fibrin formation is of considerable histological interest, owing to a possible analogy with fibril formation in connective tissue.


The contents of the lymphatic vessels is called lymph. This fluid is not identical with plasma, or with tissue fluid, yet all three are similar. Nutrient material passes from the plasma into the tissue fluid and thence to epithelial cells; and in return the products of epithelial cells enter the tissue fluid from which they may be taken over either into the plasma or lymph, first passing through the endothelial walls of the vessels. Thus in the intestine much of the absorbed fat is transferred across the tissue spaces to the lymphatic vessels (lacteals) within which it forms a milky emulsion known as chyle. This form of lymph mingles with other varieties coming from the various parts of the body, and together they are poured into the plasma at the jugulo-subclavian junction. Histologically lymph appears as a fine coagulum, containing lymphocytes and large mononuclear phagocytic cells. The cells are not abundant. Occasionally other forms of blood corpuscles are found in lymphatic vessels, but the lymphocytes greatly predominate.

Next : 1.3. Special Histology

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   Histology with Embryological Basis (1913):   Part I. 1.1. Cytology | 1.2. General Histology | 1.3. Special Histology
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