Book - Stoehr's Histology 1-2

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Lewis FT. Stoehr's Histology. (1906) P. Blakiston's Son & Co., Philadelphia.

   Stoehr's Histology 1906: 1 Microscopic Anatomy | 1-1 Cytology | 1-2 General Histology | 1-3 Special Histology | 2 Preparation of Specimens | Figures | Histology | Embryology History
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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. 'gjcjlolocry (Greek, (nSc, "a te x tile fabric") is the sdence 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 histogenesis of which may now be considered.

It has already been noted that a new human individual begins existence as gL single cell, the fertilized q , Y pm , formed by the fusion of two mature sexual cells, the spermatozoon and ovum respectively. The fertilized ovum then divides by mitosis into a pair of cells, Fig. 19, A; these again divide making a group of four, Fig. 19, B; by repeated mitosis a mulberrylike mass of cells results, called the morula, Fig. 19, C. Development to this point is known as the segmentation of the ovum.

A section through the morula is shown in 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 enlarges until the entire structure becomes a single-layered, thin- walled vesicle, within and attached to one pole of which is the inner cell mass. This mass gradually spreads beneath the outer layer until it forms a complete lining for the vesicle, which becomes consequently two layered, Fig. 19, G. The inner layer is called entoderm, and the outer layer, ectoderm.* The entire embryonic structure at this stage is called a blastodermic vesicle.

On the upper surface of the vesicle the future axis of the embryo is indicated by a thickened streak called the primitive streak. In front of this there is a groove in the ectoderm, also in the axial line of the future body. It is named the medullary groove, and just beneath it is a rod of entodermal cells called the notochord. These may be seen in cross section in Fig. 19, G and H. In G, on either side of the medullary groove and notochord a third layer of cells appears between the ectoderm and entoderm, and it gradually encircles the vesicle as did the entoderm. It is the mesoderm^ which has an obscure origin near the primitive streak.

  • The ectoderm is in part derived from the superficial cells of the inner cell mass, and in part from the primary outer layer of the vesicle. The former portion is to cover the body of the embryo, and the latter [named trophoblast] covers the fetal membranes. These membranes are to be described in a later chapter. They are omitted in the diagrams of Fig. 19.

Fig. 19. Diagrams showing the Development of thk Germ Layers. (A to F, after van Beneden's figures of the rabbit.)

A. Two-celled stage ; B, four-celled stage ; and C, morula stage of the segmenting ovum, all being surface views. D to I represent sections described in the text. The innfr crll mass and entoderm are heavily shaded ; the outer layer and ectoderm are light ; and the mesoderm is represented by dashes. Coe., coelom or body cavity. Int., intestinal cavity. Neph., nephrotome. Seg., mesodermic segment.

As it spreads out around the vesicle it divides into two layers, one of which is closely applied to the ectoderm (the somatic layer) and the other to the entoderm (the splanchnic layer) . Between them is the body cavity or coelom, which in the adult is subdivided into the peritoneal, pleural, and pericardial cavities. The ectoderm and the somatic mesoderm constitute the somalopleure, or body wall; the entoderm and splanchnic mesoderm form the intestinal wall, or splanchnopleure. The coelom has appeared in Fig. 19, H, and in I it has attained a full development. On the ventral side of the intestine it crosses the median line. Dorsally the medullary groove, which has now become the medullary tube by the fusion of its upper margins, separates the coelom into right and left portions. Fig. 19, I, may be regarded as showing the fundamental relations to be observed in the cross section of an adult, made through the abdominal cavity.

Reviewing the preceding paragraphs it is seen that the fertilized ovum through segmentation forms a morula, and later a blastodermic vesicle composed of three germ layers, the ectoderm or outer, the mesoderm or middle, and the entoderm or inner. For studying the transformation of these layers into the organs and tissues of the adult, chick embryos are more available than those of mammals. *The structure of a chick embryo of about thirty hours' incubation may therefore be briefly reviewed. Fig. 20, A, represents a dorsal view of such an embryo, various portions of which have been removed, and Fig. 20, B, is a median sagittal section of a similar embryo. On the dorsal side the ectoderm forms a continuous layer covering the embryo, and it becomes a part of the skin, the epidermis and its appendages. In the figure (A) it has been cut away except a portion folded in under the head and the part surrounding the rhomboida l sinus, rh.s . Besides the epidermis the ectoderm forms the medullary groove, the edges of which unite to form the tube beginning near the head. The union of these edges proceeds in both directions. The anterior neuropore is the last portion to close anteriorly (there are two small anterior openings in B), and the rhomboidal sinus is the expanded open part behind. Later these openings are closed over^d the medullary tube becomes detached from the epidermis. ^Its anterior part enlarges to form the brain and the two optic vesicles {op, v.), each of which it -ut rj. becomes the retina of an eye . Its posterior part forms the spinal cordThe entoderm in dorsal view is the deepest layer, exposed by removing the ectoderm and mesoderm. Under the head it forms a broad fingerlike pocket, the pharynx (ph.). Its relations are seen in the median section. Later its anterior end fuses with an inpocketing of the adjacent ectoderm to form the ^ql ^laie. When this plate becomes thin and ruptures, the pharynx opens to the exterior at the mouth. Posteriorly the entoderm envelops theyolk mass which may be regarded as occupying a distended intestine. f£he entoderm fo rms the lining of the pharynx and intestine, together with their appendages which include the lungs, liver, pancreas, and bladder these develop later. The intestine acquires its anal opening by the rupture of an anal plate, formed, like the oral plate, by the meeting of entoderm and ectoderm. The entoderm also gives rise to the notochord . a supporting rod of cells extending from the anterior end of the^rimitive streak, along the axial line to the head (B, nch,). It is the only skeletal element in some animals. In fishes it is retained as a gelatinous cord running through the bodies of the vertebrae which have formed about it, and expanding in the intervertebral spaces. In man, if it remains at all it Is vestigial in the adult. It sometimes develops abnormally, forming a peculiar tumor.

Fig. 20. Diagrams Based upon Reconstructions op a Chick of 30 Hours. A, Dorsal view. B. Median sagittal section but with the entire heart, int. n.. Anterior neuropore: ao.. aorta; ect., ectoderm; ent., entoderm; Ht., heart;, med. tube, medullary s^roove and tube ; mes. seg.» mesodermic segment ; nch., notochord ; neph., nephrotume ; op. v., optic vesicle ; p. cav., pericardial cavity; ph., pharynx; pr. St., primitive streak; rh. 8.. rhomboidal sinus; som. mes., spl. mes., somatic and splanchnic mesoderm ; v. v., vitelline vein.

Fig. 21. Transverse Section ok a 2.5 mm. Human Embryo. (After von Lenhossek.) (Compare this section with the upper part of the diagram, Fig. 19, I.) Ao., aorta ; coe., coelom ; ecL, ectoderm ; ent., entoderm ; Int., intestinal cavity ; med. t., medullary tube ; nch., "olochord; neph., nephrotome; seg., »"espdermic segment ; som., somatic mesoderm; spl., splanchnic mesoderm.

The mesoderm has been described as forming splanchnic and somatic layers which imite with one another toward the median line. Where the layers come together they are greatly thickened, and the thickened portion, by a series of transverse constrictions, becomes cut into block-like masses called mesodermic segments (protovertebrae ). They are paired structures bordering upon the medullary tube and increasing in number by the formation of new segments, chiefly posteriorly. A portion of them is seen on the right of Fig. 20, A; the rest have been removed. There is a longitudinal depression separating the segments from the splanchnic and so matic layers, and the part of mesoderm which crosses the depression is called the intermediate cell mass, or nephrolome . The coelom at first extends through the nephrotome into the segments, as shown in the cross section. Fig. 19, 1. Later the segments and nephrotome become separated from the lateral layers and from each other, and lose their cavities. This has occurred in the nephrotome of Fig. 21. vjFrom the cells o f the segments the volu nt p^r y. s tria t ed muscles are derived, and from the nephrotomes , come me JIii] urinary ducts and kidneys TJ From all parts of the mesoderm certain cells become detached, and then unite with one another by branching protoplasmic processes. Thus they form a network, in the. meshes of which is a clear intercellular fluid.

Fig. 22. Section from the Head of a Rabbit Embryo of 10^ Days, 4.4 mm., to Show Mf.senchyma.

EpI. and M. T., Ectodermal epithelium of the epidermis and medullary tube, respectively. N., nucleus; P., protoplasm ; and I. 8., intercellular substance of a mesenchymal cell. Two of these cells show mitotic figures. B. V., Blood vessel, lined by endothelium. One of the blood vessels contains an embryonic red blood corpuscle.

Such tissue is called mesenchyma (Fig. 22). It fills the intervals between the layers already described and surrounds the notochord and medullarytube. Mesenchymal cells, however, do not enter the coelom. In the chick embryo of Fig. 20, A, the greatest accumulation of mesenchyma would be found between the ectoderm covering the head and the medullary tube. Both the cells and the intercellular substance of mesenchyma undergo transformations; the latter may become a more or less solid fpialrix ^^ tius mesenchyma produces cartilage and bone , teadon , fascia , and the loose connective tissue throujB[h which the vessel«> ^^ nervef^e^^ tend. together with smooth muscle fibre

IL \}\f} splanchno pleure , between the mesodermaf and entodermal

I ij^y^ ^s, a network of blood

vessels, lined

in embryonic life (Fig. 23). Its first indication is the formation of irregular dark patches of cells, called blood islands , which surround the embryo as a mottled layer. The islands consist of cells which form the blood corpuscles, and perhaps also the lining of the blood vessek which surround them. So distinct is this vascular layer that it has been called the angioblasly and regarded as a sep arate germ layer. Usually it is considered to be defivedjroii^die mesenchyma r Aiter the angio blast has once been Seveloped n -^ it sends prolongations into the embryo to form the bloodvessels. The latter • ' thereafter never arise from mesenchymal spaces, but always as sprouts from the pre-existing vessels, growing through mesenchyma like roots through the soil. In single sections the lining of the vessels may appear inseparable from the cells around them, as in Fig. 22, but by following the vessels from section to section they will be found to be branches. The red blood corpuscles of the adul t are thought to be descendants of those which form the blood islands, f^ ey multiply in places to which they have been carried by the circulatmg blood, for example in the liver in later embryonic life, and in the red bone marrow of the adult.J^ The white corpuscle s may be derived from the same parent form as the red, or they may have several origins. The corpuscles pass out between the cells of the. vessel walls into the mesenchyma, where they wander about. Whether some of them are formed by the transformation of mesenchymal cells is still discussed. Their earliest origin like that of the vessel walls is obscure.

The vascular system in the chick embryo (Fig. 20) consists of the network in the splanchnopleure just over the yolk, from which nutriment is received by the blood. This is conveyed by the vitelline veins, one on either side, to the heart, a single median vessel under the pharynx made by the junction of the veins (Fig. 20, B). The heart divides into two aortae which pass around the anterior end of the pharynx to its dorsal side and then extend through the body posteriorly, lying und er the segments . Their branch P off Iffy to the yitellinfi jxet^^oxL U)WcoxQplelin the circujation, All future vessels in the body are branches of this simple system.

Fig. 23. Wall of the Yolk Sac (Intestine) from a Chick of the Second Day of Incubation. (Minot.)

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 Fundamental Tissues

It has been said that there are two fundamental tissues, epithelium and mesenchyma. Epithelium is a layer of cells covering an external or an internal surface of the body, having one side free and the other resting on underlying tissue. The epidermis, and the linings of the intestinal tract, of the blood vessels,, of the peritoneal cavity and of the joint cavities are all examples of epitheiium. The epidermis is ectoderm;, the lining of the intestine is entoderm; that of the blood vessels, called endothelium, is from the suigioblast; the peritoneal epit helium (m esolhelium) is part of t he splanchnic and somat ic layers of mesoderm; anTthe' Jomt cavities are lined by flattened mesenchymal cells, the cavity being, as it were, a large intercellular space. Thus epithelia are derived from all the germ layS!?^

Mesenchyma is a non-epunenaT portion of the mesoderm, which has jusPoeen described as consisting of branched cells, the protoplasmic processes of which form a continuous network. In its meshes is a clear intercellular fluid. Mesenchyma is essentially a tissue of the embryo. In the adult it is represented by connec ti ve tissue , bone, and other derivatives which preserve certain of the characteristics of mesenchy maT^

Cjbree other forms of tissue depart so far from the epithelial and mesenchymal types that they are naturally placed by themselves. These are muscle, nerve, and vascular tissue. MusdeHssm exists in three forms, of which the smooth and cardiac varieties are derived from mesenchyma and the striated (voluntary) muscles from the mesodermic segments. The epithelial character of the latter is lost. Nerve tissue is ectodermal, consisting of an epithelial tube which later becomes essentially non-epithelial, and of detached masses of cells which send processes to all parts of the body, forming the nerves. These are never epithelial. Vascular includes the blood and the lymph , which are of obscure origin, perhaps mesenchymal; also the endothelium which lines the vessels, provided that the blood and the endothelium have a common origin. It will be convenient to describe t he en tire blood vessels and lymphatic vessels in connection with their contents In the following pages the several tissues will be considered in the order above outlined. In connection with them, certain organs may be examined. ^Sn organ is a more or less independent portion of the body, having its own blood, lymphatic and nerve supply, and connective tissue framework, together with its characteristic essential c ells!;} Thus an organ should consist of several tissues. The pancreas or lungs are obviously organs. An individual muscle or a particular bone has a connective . tissue framework or covering, blood vessels and ner\'es, besides its essential , substance. Thus it is an organ. Even a blood vessel of ordinary size comes within the definition. The organs which are of wide occurrence ' like the bones, muscles, tendons, nerves and vessels, may be described with their essential tissues. The more complex organs are reserved for the later section entitled "Special Histology."

Before presenting in summary form the derivatives of the germ layers it should be noted that the ectoderm becomes continuous with the entoderm at the mouth, anus, and urogenital opening. The line of separation is not that of transition from skin to mucous membrane, but is indicated by the transient membranes (the oral and anal plates) found in young embryos. Nothing in the adult remains to show where the layers join.

Origin of the Tissues from the Germ Layers

The ectoderm produces:

  1. Epithelium of the following organs: the skin, including its 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 ureflira; together with that epithelium of the chorion which is toward the uterus and of the amnion which is toward the fetus.
  2. Nerve tissue forming the entire nervous system, central, peripheral and sympathetic.
  3. Muscle tissue, rarely, as of the sweat glands, and perhaps also some muscle fibers of the iris.

The mesoderm produces:

  1. Epithelium of the following structure: the urogenital organs except most of the bladder and the urethra; the pericardium, pleurae, and peritonaeum and the continuation of this layer over the contiguous surfaces of amnion and chorion; the blood and lymphatic vessels; and the joint cavities and bursae .
  2. Muscle 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 fetal yolk sac; and part of the urinary organs, namely most of the bladder, the female urethra, and prostatic part of the male urethra.
  2. Notochordal tissue, which disappears (?) in the adult.


Epithelium has already been defined as a layer of cells covering an external or an internal surface of the body, having one side therefore free, and the other resting on underlying tissue, epithelia differ from one another in embryonic origin in the shape of llie'ir cells, in the number of layers of cells of which they are composed, and in the differentiatip fl o£ these jcensr of these features should be recorded in any complete description of an epithelium, and, except the origin, something of each is to be observed in a single specimen. These four characteristics may be considered in order.


Epithelia arise from all three of the germ layers as described in the section on Histogenesis. The terms which may be applied to adult epithelia indicating their origin are ectodermal^ entodermal, mesodermal, mesothelial, and mesenchymal, Mesothelium is a term applied sometimes to all mesodermal epithelia except the mesenchymal. There is a tendency, however, which seems desirable, to limit its application in the adult to the pericardial , pleural, and peritonaeal epithelia. Endothelium is from the '* angioblast'* and lines the heart , the blood vessel s and the lymphatic vessels only . The loose but rather common application of this name to mesothelium and mesenchymal epithelium is much to be regretted. Mesenchymal [or false] epithelia are formed by flattened mesenchymal cells, developing in relatively late in embryonic life. They line. the bursae, tendon sheaths, joint cavities, the chambers of the eve , and the scalae tympani and vestibul iV of the ear. The table on page 26 indicates to which germ layer the epithelia belong.

Shapes of Epithelial Cells

Fig. 24. Amnion of Pig. (A Fetal Mkmbrane Covering the Embryo.) S. C. EpI., Simple cuboidal epithelium ; Mes^n., a mesenchymal tissue ; Meso., mesothelium, a simple flat epithelium.

Epithelial cells may be grouped, according to their shape, in three classes, flat, cuboidal, and columnar. These names apply to the appearance of the cells when cut in a plane perpendicular to the free surface. On surface view all three kinds are usually polygonal and often six sided. If the epithelium consists of but a single layer of cells it is called simple. Fig. 24 shows along its upper surface a simple cuboidal epithelium, The sections of its cells are approximately square. On the lower surface is a simple fiat epithelium, which, being an extension of the layer lining the coelom, is a mesothelium. A surface view of mesothelial cells on a smaller scale is shown in Fig. 25, A. Endothelium, Fig. 25, B, is quite like mesothelium in appearance; its cells, however, are usually more elongated, parallel with the course of the vessel which they line. It is a simple epithelium, so flat that the thickest part of its cell is that which accommodates the nucleus. In Fig. 26 there is both a surface view and a section of simple columnar epithelium. Often columnar cells are nearly cuboidal and are described as low columnar. Gradations between all the types described are to be expected. (The following synonyms are in common

Fig. 25.

Fig. 26. Simple Columnar Epithlium from

A. Surface view of mesothelium from the raesen- ^hf Intkstinal Villus of Man.

ter>'; B, surface view of endothelium from an A, Surface view; B, vertical section. The proraiartery. neiit cell outlines in A are due to terminal dars,

shown in cross section at the left of B, and in side view at the right.

use: cylindrical for columnar; pavement for cuboidal or flat; and squamous, meaning scale-like, for flat.)

Number of Layers

A simple epithelium may be so arranged that it appears to consist of several layers (Fig. 27). All of the cells start from the connective tissue

Fig i;. I)l\gramof PskudosiRATiFiKD Epithelium.

Fig. 2S. Stratifikd Epitmf.lhtm from thk Human Larynx, v 240.

1, Columnar cells : 2, polygonal cells: 3, Hal ( squamous) cells.

Fig. 29. 1)i:tachf.d Sqia MOLS CliLLS from THE


below, but may fail to reach the free surface. Their nuclei are at diflerent levels. Such pseudo-straiified epithelium is found in parts of the respiratory and genital tracts. A stratified epithelium is one which actually consists of several layers of cells (Fig. 28). In descriptions of stratified epithelia the number of layers should be recorded, especially if few. We may say that it is 2-layered, 4-6-layered, or many layered, as the case may be. The shapes of the cells in the basal, middle, and superficial strata should be noted. The cells are formed in the basal layer, and as they are pushed outward they become changed in shape and character. The superficial cells, for which the entire stratified epithelium is often named, may be columnar, cuboidal, or flat. The flat ones are called squamous especially when they have become detached and are found in urine or saliva (Fig. 29). (Transitional epithelium is an undesirable name for that form of stratified epithelium found in the bladder, ureter, and pelvis of the kidney. It will be described in connection with those organs.)

Network of terminal bars.

Cuticula. f

Intercellular substance.

Peripheral Differentiation

The differentiation of epithelial cells is chiefly SJ^PS ^^^^^ lines, first, the transformation of entire cells into comified masses as in the outer cells of the skin, in the nails, and hair; second, the development of various structures around the borders of the cells, particularly along the free surface; and third, the elaboration of secretion within the protoplasm. The last two forms may be considered in detail.

"Cell walls in young epithelia are generally lacking. In the early embryonic skin and in its basal layers in the adult, they are often absent, so that the cells are in very close contact. Later they become separated from one another by "cement substance," probably fluid. This is true of mesothelial and endothelial cells also. Since silver nitrate is precipitated by the intercellular substance, their cell boundaries become very distinct after treatment with this reagent. Lymph corpuscles and leucocytes may pass out from thinwalled blood vessels, between the endothelial cells, into the mesenchymal spaces. They may enter the intercellular substance between the columnar cells of the intestinal epithelium. Here they are prevented from reaching the free surface by terminal bars.

Fig. 30. Diagram ok the Network of Terminal Bars. The two cells on the left are divided lenj^thwise into halves ; the two on the right are drawn as complete cylinders or prisms.

The diagram. Fig. 30, illustrates how these bars encircle each cell near its top, binding it to the adjoining cells. The bars are regarded as a form of cement substance. In sections of the intestine, Fig. 26, or of the epidid^iS; Fig. 33, b, they may be seen with ordinary high power lensesIXPccasionally, as in the deeper layers of the skin, the spaces between the cells are crossed by delicate prptoplasmic bridges, so that the cells have a spiny appearance (Fig. 31). Fine fibrils may pass from cell to cell through these bridges which are themselves so slender as scarcely to be defined without oil immersion objectives. The spaces are smaller and the .bridges shorter in simple than in stratified epithelium. Therefore the spaces have been regarded as canals to convey nutriment to the outer cells. Nutriment copaes to 1 O epithelia through blood vessels in the tissue just beneath them^) Except possibly in the bladder and renal pelvis the vessels do not enter an epithelium, nor are lymphatic vessels found within Jt) (Whatever nutriment the outer cells receive must come through the cells below or through the intercellular spaces Intercellular spaces have been said to arise through coalescence of vacuoles in the exoplasm. The fact that the spinous cells, with intercellular substance between them, present a form intermediate between ordinary epithelium and mesenchyma has been emphasized. The basal cells of an epithelium sometimes seem to send out processes which connect with the underlying mesenchymal cells. In glands especially, a thin, well-defined membrane is often found just under the epithelium, and it is called a basement membrane (membrana^^ro^a) . It is usually homogeneous and without nuclei, often being of elastic substance. Some basement membranes are held to be formed by the basal processes of epithelial cells, but generally they are considered of mesenchymal derivation.

(along their free surface, epithelial cells often have a thick wall called a cuticular borde r (top plate, or if very thick, a crusta). Under high magnification some cuticular borders appear perpendicularly striated and consist of protoplasmic processes or pseudopodia, which may be sent out or retracted, thus causing the border to vary in width. This has been observed in the human large intestine, and in the efferent ducts of the testis of a mouse. Fig. 32, a and b. x Longer processes which are vibratile but not retractile are known as cilia . They cover the free surfaces of many epithelia either simple or stratified. In the living condition the motion of cilia may be observed in certain unicellular animals, along the gills of fresh water clams or in pieces of oral epithelium from a frog. The stroke of cilia is eflfective in one direction only, so that mucus or solid particles may be swept by their action across the surface of the epithelium, for example from the trachea to the mouth. In the lower animals the stroke may be reversed under certain conditions. Ordinarily the student can merely detect the presence or absence of cilia in a given specimen. Under favorable conditions investigators have observed that each cilium is connected with a granule or pair of granules, the basal body, near the upper surface of the cell, and several agree that these arise by division of the centrosome. In Fig. 32, a, the cell contains a single diplosome (centrosome) in characteristic position; b has four diplosomes; and c is ciliated with basal bodies similar to diplosomes. Apparently no ciliated cell has been observed in mitosis. Fig. 33, a, is a diagram to show that cilia may extend through the top plate into the protoplasm, and obscure modifications of the upper part of the protoplasm may sometimes be seen with ordinary magnification. The row of diplosomes may appear to form a single or double transverse line.

Fig. 31. Intercellular Bridge as seen in Vertical Sections OF THE Gp:rminative Layer OF THE EpIDERMIS.

Fig. 32. Cki.lsofthh Efferent ducts of the Testis of a Mouse. (After Fuchs.) To show terminal bars; cuticular border (in b); diplosoffles; and cilia (in c).

The cells known as spermatozoa are each provided with a single, very long, motile process, such as is called a flagellum. It develop s in relation to the centrosome, as will be described in connection with the testis. Some so-called cilia are non-motile prolongations of the filar mass of the protoplasm, and seem to be concerned with the discharge of secretion. They have no basal bodies and lack the distinctness of true cilia, generally appearing in conical clumps like the hairs of a wet paint brush. Such cilia are found in the epididymis (Fig. 33, b). In certain of the the epididymis kidney cells they cells there are short, thick, non-motile processes, described sometimes as rudimentary cilia, sometimes as a cuticula, and known as the "brush border. The cells which line the central canal of the nervous system develop processes which are not true cilia. Finally, in what is called neuro-epithdium, as in the taste buds, the epithelial cells have one or more slender processes apparently designed to receive stimuli, and the function of the neuroepithelial cell is to transmit this stimulus to the nerve fibers which branch around its lower part.

Fig. 33a, Diag:ram of a ciliated cell (after Prenant). showing vibratile cilia; b, cells of the human epididymis (after Fuchs), show in m n-moiile cilia.

Processes of Secretion

Many cells can elaborate and discharge certain substances which do not become parts of the tissue. Such cells are called glands and their products are either used in the body (secretions) or, being of no value, they are removed (excretions) The processes of elaboration and discharge of either secretion or excretion may often be recognized by changes in the form and contents of the cell, indicating that it is empty or full of secretion, as the case may be. A gland cell which is full of elaborated secretion 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 of secretion differ in two types of gland cells, the serous, which produce a watery secretion like that of the parotid salivary gland, and the

Fig. 34. Two Skrois 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.

I mucousy which form a thick secretion such as occurs in the nose and throat.

The nucleus of empty gland cells often has a fine chromatin network together with distinct nuclear granules. The granules are lacking when the cell is full of secretion and the chromatin takes the form of coarse fragments. Doubtless the granules pass from the nucleus into the protoplasm, but whether they become true secretion granules is uncertain, since similar phenomena have been observed in nerve cells.

The protoplasm of serous gland cells at the beginning of secretion exhibits distinct granules, coarser than microsomes, staining intensely with certain dyes (Fig 34, A). The granules enlarge, lose their staining capacity, and are transformed into drops of secretion with which the cell becomes charged. As a whole, the cell is larger and clearer than before.

Fig. 35. Epithelial Cells Secreting Mucus. From a section of the mucous membrane of the stomach of man. X 560. p. Protoplasm ; 8, secretion ; a. two empty cells ; the cell between them shows beginning mucoid metamorphosis; e, the cell on the right is discharging its contents ; the granular protoplasm has increased and the nucleus has become round again.

The fluid secretion and sometimes the granules are discharged from the free surface.

Such cells are striking examples of the ^g/g^2ig cells, by which is meant a differentiation of protoplasm along the axis of the cell. The basal portion receives the nutriment to be made into secretion. It often exhibits striations, rods, or filaments known as ergastoplasm (Fig. 34, A). The distal portion which contains the elaborated product is obviously of a diflferent nature. Very many kinds of cells give evidence of polarity. The nuclear constituents also may be arranged in relation to this same axis or to another, but nuclear polarity which is manifest during mitosis may be disguised or lost at other times.

In mucous cells as in serous, secretion begins with granule formation. The granules soon change into clear masses of mucus, which accumulate toward the free surface and are more or less sharply separated from the unchanged protoplasm beneath. The mucus is, however, penetrated by strands of protoplasm which contain the centrosome. As elaboration of mucus continues the nucleus is crowded to the base of the cell, and may become round or flattened (Fig. 35). Then the secretion is gradually discharged, apparently with the rupture of the top plate. If the cell is not destroyed the nucleus returns to its central position and the protoplasm refills the cell now greatly reduced in size. Most gland cells are not destroyed by the discharge of secretion, but may repeat the process several times. In the sebaceous glands, however, cells and secretion are cast off together, and many of the mucusproducing goblet cells, such as have just been described, are thought to perish after once filling with secretion. In the large intestine, goblet cells are formed near the bottom of tubular depressions in a simple columnar epithelium. Fig. 36. By the addition of new cells below them, they are pushed toward the outlet of the tube where the oldest cells are found. Mucus is discharged while its formation continues. For a time the secretion develops faster than it is discharged, so that it accumulates within the cell (Fig. 36, 2), but later, as elimination exceeds production, the cell becomes emptied and dies (Fig. 36, 4). In stratified epithelium, mucus may be formed in the deeper cells, but it cannot be discharged until these have reached the surface.

Fig. 36. Intestinal Gland from a Section of the Large Intestine of Man. X 165.

The secretion formed in the goblet-cells is colored blue. In zone 1 the globlei-cells show the beginning of secretion ; that expulsion has bejarun is evident from the presence of^ drops of secretion in the lumen of the gland. 3, Goblet-cells with much secretion. 3, Goblet-cells containing less secretion. 4, Dying goblet-cells, some of which still contain remnants of secretion.

The Description of an Epithelium.

I , In describing an epithelium the student should record its origin if it is remembered, and should note from observation, first, the number of layers (whether the epithelium is simple or stratified; in the latter case,

, the number of strata) ; second, the shapes of the cells (columnar, cuboidal, or flat, and in a stratified epithelium the layers, basal or superficial, in which such shapes occur) ; finally, the special structures should be sought, including basement membran es, intercellular bridges, terminal bars, striated, brush , or striated border, and forms of secretioin within the protoplasm. A detailed description of nucleus any protoplasm should be given of such epithelial cells as are of special importance.

The Nature and Classification of Glands

A preliminary description of glands may be inserted at this point, since glands in the strictest sense are groups of such secreting epithelial cells as have just been described. ^Two other classes of structures are called glands, however. In one of these, cells instead of secretions are formed and set free. Cell-producing glands are called specifically cytogenic "TT* SiS^UiS- These include, first, the ovary and testis^ which produce sexual cells; and, second, the lymph glands, haemdjmph^ glands, sp leen^ and jed bone inarrow, all of which produce blood corpuscles. Tissue similar to that of the lymph glands when found in a diffuse form is not called glandular, but merely lymphoid tissue. The term gland, as here employed, suggests a well-defined, macroscopic mass of cell-producing tissue, epithelial in the sexual glands, and non- epithelial in the lymphoid grpu^

Excretory duct.

Besides the cytogenic glands, there are e fUhdioid glands consisting of clumps or cords of cells resembling epithelium, yet having no free surface. These masses of cells, which may be detached from an epithelium or formed from mesenchyma, are generally penetrated by blood or lymphatic vessels into which their secretions are discharged. Secretions eliminated in this manner are called internal secretions ^ The epithelioid glands can produce only internal secretions. The suprarenal gland is a large example of this class?^

Epithelial glands are such as consist of true epithelium, discharging their secretions from its free surface. Most glands are of this nature. In simplest form they are merely the occasional mucous or other secreting cells found scattered over an epithelium. These are sometimes called unicellular glands. Others are simple tubular or saccular depressions in the epithelium, lined with secreting cells as shown in Fig. 36. Glands of this description, perhaps coiled at their lower end, or having a few branches, or consisting of a cluster of saccular secreting spaces, often occur in large numbers as parts of some organ. Thus they are found in the intestine, the uterus, and the skin, where they are named intestinal glands, uterine glands, sebaceous and sweat glands respectively, each kind having its special characteristics, ^liey are named as classes and not as individuals, and have been grouped as the simUe ({ If^nds, JOn the other hand, there are epithelial glands which occur singly or m circumscribed groups, having their own connective tissue capsule, blood, nerve, and lymph supply. Such forms are considered as separate^rgans, for example, the liver, pancreas, mammary gland, and^rostate, and for this group the name compound glg nds has been introduced!)

Fig. 37. Diagram of the Development of a Compound Gland. The arrangement of ducts in is that of the human submaxillary gland.

These glands develop in the embryo generally as a solid downgrowth of the epithelium. ("This divides by branching, and subdivides as shown in the diagram, Fig. 37, A, B, and C. A cavity appears in the cord of cells which then become clearly epithelial. Simple glands, as in the intestine, may remain in the stage A, and be lined throughout with secreting cells; in glands of greater size and complexity only the terminal portions contain the essential secreting cells. The trunk and its main branches serve to convey the products of the "end pieces" to the surface, and constitute the ducts. Stage B is permanent in such simple glands as those of the stomach, in which a short duct without branches is formed by the union of a few tubular end pieces^ The compound glands generally have branching ducts as in C and D. )

The secreting portions of the gland may be tubular, spheroidal, or of some intermediate shape. A round termination is called either an

acinus (Latin, a grape) or an alveolus (Latin, a small rounded vessel). The intermediate forms are called alveolo-lubular [tubuloacinar, etc.]. The cavity of these parts is called the lumen of the gland, and is directly continuous with the cavity of the ducts. The secretion may pass from the cells directly into the gland lumen, or it may enter extensions of the lumen found either between the cells or actually within their protoplasm. These are the intercellular and intracellular Fig. 38.-D1AGRAM OF A Simple al- secretorv capillaries respectively. They may

VEOLAR Gland, Showing Inter-branched or anastomosing, that is, formTHE ig networks by the union of their branches.

The intracellular capillaries have less distinct walls than the others, and are considered transient formations related to vacuoles. The diagram, Fig. 38, represents one half of a simple alveolar gland with intercellular secretory capillaries on the right, and intracellular ones on the left. Both kinds are found in the sweat glands, the liver, and the gastric glands. Intercellular capillaries only are found in the serous glands of the tongue and in the serous portions of the salivary glands, also in the bulbo-urethral, pyloric and lachrymal glands. Secretory capillaries are apparently absent from mucous, duodenal, intestinal, uterine and thyreoid glands, and from the kidney and hypophysis.

Having reached the gland lumen, the secretion may pass into a narrow duct lined with simple cuboidal or flat epithehum, the intercalated duct of Fig. 37, D. The transition from this to the larger duct, lined perhaps with columnar epithelium, is not as abrupt as in the diagram. In certain glands the cells here show basal striations, due to rows of granules, which indicate that this portion of th e du cts produces a secretio n. The terminal part of the ducts of a large gland may be formed of stratified epithelium, perhaps containing mucous cells. The ducts of the liver produce a considerable quantity of mucus, and the bronchi, which from their develop ment and form may be cons) der<^<;^ the f^n^-^c r^f tht^ ^"ng*^, contain scattered mucous cells and small secondary mucous glands. Important secretions are elaborated by the efferent and some other ducts of the testis. In the kidney there is no terminal secreting "pbrtTon as in most glands. The duct-like tubules serve rather to transfer selected materials from the blood to the lumen than to form new substances. This is more obviously true of the alveoli of the lung which merely transmit oxygen and other substances through inert modified cells. Morphologically, that is, in their form and development, both the kidneys and the lungs are glands.

All epithelial glands arise as outgrowths from an epithelium, as has been described. A few, by the obliteration of their ducts, become separated from their place of origin. This occurs in some small glands associated with the brain and in the thyreoid gland. The closed end pieces of the thyreoid become filled with a secretion that cannot escape. Derived from or in addition to this, there is an internal secretion which is taken up by the vessels adjacent to the basal surfaces of the cells.

For completely 9l9sed epitbdirll f^^r?i t such as occur in the thyreoid gland aM M tUfe 6varv. t he term joduTe^ is used (Latin, jolliculus, "a little bag"). If such closed spaces are^ainological or degenerative, they are called cysts. Small round solid masses of lymphoid tissue, occurring singly or as parts of lymph glands, are called nodules (Latin, nodulus,

    • a little knot"). Very often and improperly lymph nodules are called follicles.

In examining sections of glands the student should observe to what dass tliey belong, and should record in case of epithelial glands whether they are unbranched or branched, together with the shape of the endj ; ^iere«=; . It is often difficult to determine this shape without resort to reconstructions from a series of sections. The various appearances of the ducts should be studied with the idea of picturing the gland as a whole.

As a summary of the preceding paragraphs the following tabular classification of glands may be presented:

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

I. Unicellular glands. (J^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. j^sodermaK e. j^.^ epididymis and kidney .

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

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

a. Ectodermal, pineal body ; both lobes of the hypophysis.

b. Entodermal, thyreoid gland.

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

a. Ectodermal (through their relation to the sympathetic nerves ), glomus caroticum; glomus coccygeum; and medulla of the suprarenal gland.

b. Mesodermal, cort ex of suprarenal gland; interstitial cells of the testis; corpus JuteunT

c. Entodermal, islands of the pancreas; epithelioid bodies in relation wit h the thyreoid glahH;" thymus in its early stageg.

IV. Cytogenic glands, producing cells.

a. Mesodermal, epithelial, th e ovary and testis

b. Mesodermal, mesenc hymal, the lymiph glands, haemolymph glands, spleen, red bone marrow, arid many smaller structures.

The Mesenchymal Tissues

In an early stage the embryo is composed of two tissues, epithelium and mesench)mia. Mesenchyma has already been defined as a non-epithelial portion of the mesoderm composed 0} branching cells. Their protoplasmic processes atuistomose, forming a continuous network of protoplasm, a syncytium, in the meshes of which is a homogeneous intercellular substance or matrix (Fig. 22, page 23). Those derivatives of mesenchyma which diverge greatly from this embryonic type will be reserved for later consideration. Such are the vascular systems, smooth muscle and certain epithelioid cells. Reticular tissue^ mucous tissue, connective tissue, tendon, cartilage and bone, sometimes grouped as the supporting tissues, may now be considered in turn. They are all mesenchymal tissues which have undergone transformations both of their cells and of the intercellular substance.

Reticular Tissue

Reticular tissue is that form of adult tissue which most closely resembles mesenchvma. It is a network of cells with a fluid intercellular substance.(^The protoplasmic processes, however, have been transformed into stiff slender fibrils containing a substance known chemically as reiiculin.) Whereas ordinary connective tissue may be made to yield geTailn, reticular tissue gives both gelatin and reticulin. Since connec ive and reticular tissues occur so closely associated that it would be difficult to obtain pure specimens of the latter, the gelatin has been ascribed to a mixture with connective tissue elements. On the other hand, it has been asserted that, reticulin is merely a variety of gelatin due to the method of analysis. (Reticular fibers, by their greater resistance to pancreatic ' digestion and by dissolving in dilute acid, differ from the elastic elements of connective tissue.^ They are said to be more resistant to acids or alkalies \ than the fibrillar part of connective tissue. Such a distinction is hard to establish, especially since some reticular tissues are more resistant than others, Chemically, therefore, the validity of reticulin is question We TXj histologically reticular tissue is quite clearly defined by^ the abundance and fluidity of its matrix. Small round cells, the lymphocytes, which may be scattered through ordinary connective tissue, are always abundant in the meshes of reticular tissue. They are so numerous and closely packed that the delicate reticular fibers are mostly hidden, and can be studied to advantage only after the loose cells have been disengaged from their meshes. This may be accomplished by shaking or brushing the sections, or by artificially digesting: the specimen (which destroys the fig. 39.-reticular

Tissue from the reticular cells along with the others, but leaves the fibers) / spleen of the pig.

 n.. Nucleus; f., fiber, of 

or by the method of Prof. Mall, used in obtaining Fig. ^g. retjcuim ; i. §.. intercellular Space.

A piece of fresh spleen was distended by injecting gelatin into its substance; then frozen and sectioned. The sections were put in warm water which dissolved out the gelatin, ca^ying the loose cells with it, and leaving areas of clear reticular tissue, ( in^ord inary sections the student will recognize reticular tissue by the cells in its meshes, but some of its nuclei and fibers can always be detected upon close examination. It may contain cells other than lymphocytes, for it forms the framework not only of lymph glands, but of red bone marrow and the spleen. A layer of reticular tissue is found under the epithelium of the digestive tract, and it has been reported in many organs.

Mucous Tissue

Mucous tissue forms the substance of the umbilical cord, where it was formerly called Wharton's jelly. There it occurs as a gelatinous tissue of pearly luster, containing neither capillary nor lymphatic vessels, nor nerves. In the umbilical cords of young embryos it closely resembles mesenchyma. At birth its cells, which retain their protoplasmic connections with one another, appear fusiform (spindle-shaped) or triangular rather than stellate. The intercellular substance consists of fibrils in irregular bundles, embedded in a matrix containing mucus. It has long been debated whether these fibrils originate in the matrix directly, by a sort of precipitation or coagulation, or develop in the outer protoplasm (exoplasm) from which they later become separated. The tendency is toward the latter interpretation. In specimens specially stained, Fig. 40, the protoplasm may present a sharp fibril-like border staining differently from the intercellular fibrils. Chemical changes in the fibrils may occur after they have left the cells. Elastic fibers, to be described under connective tissue, are not found in the mucous tissue of the umbilical cord.

The mucins are a group of compound proteid bodies containing a carbohydrate complex in their molecule and therefore known as glycoproteids. There are many varieties, the mucus of gland cells and of the mucous tissue just described both containing true mucins. Related substances, called mucoids, have been obtained from ten Fu;. 40 Mucous Tissue from the Human ^^v^ pRrtilflcrp and hone The develoDUmbilical Cord, at Birth. Mallorys con- ^^"> CanUdgC anu UOnc. X UC UCVClup

ment of mucus by connective tissue cells does not produce anything corresponding with goblet cells. It is only in connection with other sorts of secretion that connective tissue cells are said to elaborate granules which are converted into vacuoles.

All embryonic connective tissues are thought to contain mucus, and a variety of tumor (myxoma) is of this type. The peculiar connective tissue of the cornea, to be described in connection with the eye, contains no elastic fibers and isj:ich in mucin; nevertheless its structure is very different from that ofi, the substance of the umbilical cord, to which the name "mucous tissue is particulary applicable.

nective tissue stain, d. f., Dense bundle of fibrils ; m., mucus containing intercellular substance; l.f., loose fibrils; c, cell with fibril-like border.

Connective Tissue

Connective tissue is that derivative of mesenchyma which consists of cells either connected with one another or disconnected, and of intercellular spaces largely occupied by fibers of two sorts, white and elastic fibers respectively. In the dense forms of connective tissue the fiber-bundles tend to be parallel and are closely packed. In loose or areolar connective tissue the fibers run in various directions, and among them are cells which have become charged with fat. When these are numerous they constitute jot tissue (adipose tissue). Areolar connective tissue ordinarily contains fat cells. In every specimen of connective tissue three features should be examined: the fibers the cells and the remains of the intercellular substance.


If a small piece of fresh connective tissue, such as envelops the muscles of a guinea pig, be pulled apart on a shde and examined in water, it will exhibit the structures shown in Fig. 41 . Most of the specimen may be obscure, but in such parts as were properly spread out the white fibers can be seen as pale, wavy bands, without sharp borders. They are faintly striated longitudinally, due to the fact that they are bundles of minute fibrils bound together by a small amount of cement substance. The addition of picric acid causes them to separate into their constituent elements. The white fibers divide, as shown in the figure, by the separation of the fibrils into smaller groups; the fibrils themselves do not branch. If dilute acetic acid is put upon the specimen, these fibers swell, as shown in Fig. 41, B, often presenting a series of constrictions ascribed to the remains of encircling cells, to rings of elastic fiber, or to remnants of a sheath which enveloped the bundle. Ultimately the white fibers disappear in acids or in alkalies. Chemically they are said to consist of collagen, an albuminoid body which on boiling yields gelatin (glutin, the source of glue). The white fibers are supposed to arise in the exoplasm. Those seen in mucous tissue were of this variety.

Elastic fibers are probably always present in connective tissue, though varying greatly in their abundance. They are said to develop later than the white fibers and are absent from corneal tissue, mucous tissue, and generally, though not always, from reticular tissue. In Fig. 41 they are seen as sharply defined, straight or stifly bent, homogeneous structures

Fresh Connective Tissue from Around the Shoulder Muscles of a Guinea Pig. A, Before and B, after adding dilute acetic acid. El. F., Elas" ", while fiber ; n., nucleus of connective tic fiber; Wh.F., tissue cell.

which are highly refractive, that is, they so reflect light as to change from bright to very dark objects on varying the focus. They may be extremely fine, or quite broad, but the latter are not divisible into smaller elements or fibrils. Seen in specimens which have not been torn apart, the elastic fibers form a network, Fig. 42, A, and the smooth manner in which they fuse at its angles is characteristic. When the net is broken the fibers retract in irregular spirals. The elastic fibers are thought to be of exoplasmic origin, as is suggested by Fig. 42, B. Elastic substance may appear within the cell as ments, or as granules which later fuse, some cases the fibers forming the elastic net are wider than its apertures, as shown in the lower part of Fig. 43, A. Here they constitute a perforated elastic plate, called a fenestrated membrane, and such occur in many blood vessels) B and C of the same figure present elastic elements from the ligatnefttum nuchae, a structure containing relatively little white fiber, and hence used for the chemical analysis of elastic fiber. The stylo-hyoid ligament and the ligamenta flava are also elastic ligaments.

Fig. 42. 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 fetal pig. (After Mall.)

Fig. 43. Elastic Fibers. A, Network of thick fibers below, passing into a fenestrated membrane above. (From the endocardium of man.) B, Thick elastic fibers, f, from the ligamcntum nuchae of the ox; b, white fibers. C, Cross section of the ligamentum nuchae, lettered as in B.

Elastic fibers are not destroyed by dilute acids (Fig. 41, B) or alkalies. They consist of elastin, an albuminoid body which does not yield gelatin on boiling. Because of the difference in chemical composition, elastic fibers may be stained with dyes which fail to color white fibers: thus resorcin-fuchsin stains them dark purple, but scarcely affects the white fibers; on the other hand, Mallory's connective tissue stain makes the white fibers deep blue, the elastic elements remaining colorless or pale pink. These special stains are of the greatest importance in stud)ang connective tissue. In ordinary specimens white fibers appear blended in masses and the small elastic fibers are invisible. There may be other sorts of fibers than the white and elastic, such as the fibroglia of Prof. Mallory, but these are still very little understood.


Usually the cells of connective tissue are conspicuous only through their flattened nuclei, which are broadly elliptical on surface view, and rod shaped when seen on edge. The protoplasm forms a wide, thin layer, and since it is closely applied to the fiber bundles which it may encircle, and ordinarily stains like them, very often it can scarcely be distinguished. As a whole, the cells are irregularly polygonal, flattened, and bent to conform with the fibers. In ^ ' some lamellar tissues these flat cells are in contact with one another along their edges, thus simulating an epithelium. In loose connective tissue they may be widely separated. They possess processes which may or may not unite with those from other cells, and in their proto- neSus fat^cSlls. hlman

Fetus of Five Months.

plasmic bodies there are often a few small fat n., Nucleus; t. v.. fat vacuole; p. r..

J -t . protoplasmic rim.

Fat cells, as may be seen in the subcutaneous tissue of a five months' fetus (Fig. 44) arise from mesench}'Tnal cells by the development of vacuoles of fat within their protoplasm. The vacuoles enlarge and coalesce, so that the nucleus is crowded to one side, lying in a rim of unaltered protoplasm. Gradually the protoplasmic processes disappear. The resulting form of cell has often been compared with a "signet ring," referring to its appearance when seen in section. The vacuole of fat further enlarges so that the nucleus is flattened and the protoplasmic layer becomes very thin. In fresh cells it cannot be seen. The entire structure appears as a large refractive drop of oil, Fig. 41, spheroidal if occurring singly, or polyhedral if compressed by adjoining cells. Small fat drops may be scattered through the specimen due to rupture of the cells. In order to study fat in sections it is necessary to employ special reagents. The tissue may be preserved either in osmic acid which blackens the fat, or in a formalin solution and afterwards stained with Sudan III or Sharlach R, which color the fat droplets red and demonstrate them even when minute. In ordinary sections all the fat has been dissolved by treatment with alcohol, leaving the protoplasmic rims enclosing empty spaces. The spaces, however, correspond in size and shape with the droplets of fat which have been removed. Provided that the cells have not collapsed, they appear as large, round or polygonal structures (Fig. 45). Some are seen in surface view, as if looked do\\Ti upon, and may show a broadly elliptical nucleus containing perhaps one or two small vacuoles. Most of the cells in thin sections are cut across. The protoplasmic rim, reduced to a line, may be seen to widen and enclose the nucleus, but often no nucleus is found. This is because the fat cells are so large that they may be cut into several slices, only one of which carries with it the nucleus. Filling the spaces between the cells there is more or less connective tissue containing blood vessels. The student should distinguish the nuclei within the fat cells from such connective tissue nuclei as may be closely adjacent to them. In some sections, radiating slender crystals, often ill defined, will be seen within the fat vacuole. These are fat crystals [margarin crystals] which formed as the fat cooled and solidified; in the living body fat is fluid.

Surface view of fat cells, in the nuclei of which fat droplets are visible.

Connective tissue Blood vessel containcells. ine corpuscles.

Fat cell and its nucleus in side view. Blood capillary. Connective tissue.

Fig. 45. Fat Tissue from the Human Scalp.

All fat cells do not contain a single large vacuole. As described by Dr. H. A. Christian there occur both at birth and in the adult such fat

Fig.. 46. Fat Gems from Near the kidney of a new-born Child.

cells as are drawn in Fig. 46. Their protoplasm contains a number of large vacuoles and the nucleus is sometimes central. Such cells may be found in subcutaneous tissue, but are more often seen in the omentum / or around the kidneys. In extreme emaciation the fat cells become flattened and several small vacuoles replace the one large one. These cells are said to produce a mucoid substance appearing both between and in the cells

Fat cells develop in the fetus in lobular groups around small blood vessels. They are always foimd under the skin, behind the eye and in other definite places, so that they have been regarded as secretory organs. Like gland cells they take material from the vessels near by, either fat which is stored with but little change, or sugar and probably albuminoid bodies which are transformed into fat by the activities of the cell. The process has been said to begin in or near the nucleus with the formation of granules, which disappear a3 the vacuoles develop aroimd them. The small vacuoles in the nucleus have been described as containing an alkaline fluid which is not fat, and which is discharged into the protoplasm. They are also described as fat droplets and are observed in cells full of fat rather than in those beginning its formation. Like an internal secretion, fat is taken from the cells into the vessels, though probably not in the form in which it is stored. It should be remembered, however, that most cells take material from the blood and transform it into new substances. They also very generally may effect the body by the products of their activity. Unless the term "gland cell" is to be so extended as to lose its significance, lobules of fat should not be considered glands. fig. 47 -fat Cells from the

Axilla of an Extremely Emaciated Individual.

Besides the mesenchymal cells which early x 240. k, Nucleus ; f, fat droplets ; c, cap become differentiated mtO fat cells, the cells of illaryblood vessels; b.connec

live tissue.

adult connective tissue, of cartilage, and the epithelium of the liver all form fat vacuoles which may or may not coalesce. Pathologically fat appears in many kinds of cells, sometimes representing an accumulation of nutrient material which the cells are unable to assimilate, sometimes resulting from the breaking down of the normal combined fats into vacuoles of free fat. (^t is customary to speak of such cells as fatty liver cells, cartilage cells containmg fat," etc., and to restrict the term **fat cell" to those of mesenchymal origin distended with one or a few large vacuoles.

Pigment cells are cells of mesenchymal type the protoplasm of which contains colored granules. The granules, which are generally unaffected by stains, appear brown or black in sections, and are composed of melanin in some of its various forms. The changes of color in the chameleon are largely due to the contraction or extension of the processes of such pigment cells. In man this type of cell is of limited occurrence, being found chiefly around the eye (Fig. 48, A). The same sort of pigment may be found in epitheUal cells. Thus it appears in the epithelium of that part of the conjunctiva which covers the bulb of the eye in the guinea pig (Fig. 48, B), and as has recently been noted, it occurs there in all human races but the European. The pigment of the skin in the negro races and of the nipple in others is of this sort. It has been discussed whether such pigment arose in epithelial cells or was transferred to them from underlying connective tissue cells, or actually remained in such underlying cells (Fig. 48, C). The retina affords positive evidence that pigment may develop in epithelial cells, and it has even been said that some of these become detached and send out branches. The term "pigment cell'* as ordinarily used refers to a branched cell of mesenchymal origin. Others are said to "contain pigment granules," or to be "pigmented epithelial cells. Finally, it should be added that the melanin series of pigments is one of three which give color to the body. The others are the fat pigments, or lipochromesy and the blood pigments, or haemoglobin derivatives. Cells containing these other pigments are seldom called pigment cells.

Fig. 48. A, Two pipnent cells from the deep, peripheral part of the cornea of the rabbit. B, Pigmented epithelium from the conjunctiva of the guinea pig. The pigment is chiefly in the basal layer. C, Pigment cells sending processes between the epithelial cells of the skin of an embryo lizard, Lacerta. (After Prenant.)

Besides the pigment ceUs, fat cells, and fiber-producing cells {fibroblasts) several other forms occur in the meshes of connective tissue. These are free from one another and are merely lodged in the connective tissue meshes. Some of these cells emigrate from the blood vessels in adult life. Others may be descendants of cells which emigrated from the vessels in the young embryo, or else they may have arisen directly from mesenchyma in the neighborhood of the vessels. A more definite statement concerning them is not justified. The free cells in connective tissue have been recently classed as lymphocytes, plasma cells, ^'resting wandering cells,'* mast cells, and eosinophUes. All of these types' except the resting wandering cells are well known and generally recognized.

Lymphocytes (Fig. 49, 1) are a form of blood corpuscle consisting of a round nucleus containing block-like masses of chromatin, and of a narrow rim of protoplasm. Plasma cells (Fig. 49, p) are derived from lymphocytes by an increase in their protoplasm which stains deeply with most stains, but especially with basic dyes such as methylene blue. It is a dense protoplasm which contains no distinct coarse granules. A clear area around a diplosome or a group of centrosome granules may be found in favorable specimeils. The resting wandering cells (Fig, 49, r. w.) are said also to be derived from lymphocytes. They reseipble connective tissue cells (fibroblasts) but do not produce fibers. Their nuclei are smaller, darker, and more irregular. Their protoplasm, which extends in irregular processes, contains scattered coarse granules staining deeply with basic stains. These cells have been called clasmahcytes. In amphibia there are connective tissue cells with slender processes full of granules. These are described as producing detached fragments, and so were named clasmatocytes. In mammals the fragmentation has not been observed and the **clasmatocytes" are so different from those of amphibia that the term is scarcely applicable. The resting wandering cells or clasmatocytes have been considered varieties of mast cells. The mast cells (Fig. 49, m) are characterized by coarse protoplasmic granules staining intensely with basic stains. These granules are soluble in water and are poorly preserved in ordinary sections Eosinophiles (Fig. 49, e) also have coarse granules, but they do not stain with basic dyes; they have great affinity for acid stains, particularly eosine. Their nuclei are round or indented.

The free cells of connective tissue occur especially along the courses of small blood vessels. They will be better understood by the student after examining blood, for they are closely related to the white corpuscles to be described later. All forms of blood corpuscles are to be found at times in the meshes of connective tissue.

The intercellular spaces of connective tissue are of special importance. Between the fibril bundles, the cells and the elastic network, there remain spaces filled with fluid. They are extensive in reticular, mucous, and loose connective tissue, but are reduced to slender channels in the dense forms. Fluids circulate in them, conveying nutriment from the vessels to epithelial and other cells and conducting waste products back to the vessels. White blood corpuscles pass out between the endothelial cells of the vessels to enter these spaces in which they may travel about or multiply. Some corpuscles may originate in them, formed from adjacent connective tissue cells. The intercellular or tissue spaces (lymph spaces) differ from small vessels, either blood or lymphatic, in having no endothelial walls; and the tissue fluid which they contain ordinarily differs from either the blood plasma or the lymph. It undoubtedly resembles lymph with which it has been considered identical.

Fig. 49. The Cells of Loose Connective Tissue, the Lowest Row from a Rabbit, the Rest from a Guinea Pig. (After Maxhnow.) e., Eosinophile; f., fibroblast; I., lymphocyte; m., mast cell; p., plasma cell ; r.w., resting wandering cell. The nuclei are usually round.

Summary of connective tissue. Connective tissue consists of intercellular spaces and fluid, white fibers, elastic fibers, and cells. It surrounds the various organs, and through it pass the nerves, blood and lymphatic vessels. Its spaces are intermediate paths between the vessels and the cells of the organs. Its elastic fibers which though varying in size are not divisible into smaller elements, form slender networks or coarse fenestrated membranes, and are of exoplasmic origin. Its white fibers are bundles of fibrils cemented together, and either densely packed or loose and areolar. Its cells are those which produce the fibers, together with fat and pigment cells, and various forms lodged in the intercellular spaces. These include lymphocytes, plasma cells, resting wandering cells, mast cells, and eosinophils.


Tendons consist essentially of very dense connective tissue with parallel fibers. The dense tissue as seen in cross section, Fig. 50, is covered by a sheath of ordinarj' connective tissue, prolongations of which extend into the substance of the tendon. There .they unite to form a network of partitions or septa. This ordinary connective tissue contains nerves which supply the tendon, to be further described on page 103; also blood vessels in relatively small number, and lymphatic vessels which are confined to the outer sheath. The septa surround bundles or fasciculi of tendon fibers, called "secondary tendon bundles" in distinction from the smaller "primary bundles" of which they are composed. The latter are groups of fibers more or less definitely surrounded by wing-like processes of the tendon cells, which appear as dots in Fig. 50, but are clearly shown in Fig. 51. The tendon cells are characterized by their compressed branches which extend between and around the fiber bundles, anastomosing with similar branches of neighboring cells. The fibers are white, consisting of collagen (the gelatin-producing substance) and of tendo-mucoid which may be found in the cementing matrix. Elastic elements are said to occur in small quantity especially near the cells and their processes. Intercellular spaces are very small and are not shown in the figure. In longitudinal sections. Fig. 52, the parallel arrangement of the fibers is apparent, and the nuclei are in rows. The protoplasm is often indistinguishable, but in special preparations from delicate tendons it appears as a thin folded layer with plate-like projections, Fig. 53.

Fig. 50. From a Cross Section of a Tendon from an Adult Man. X40.

Fig. 51. FgoM the CalcaNEAN Tendon [Tbndo] OK A Rabbit. ( After Prenant.)

p. b.. Primary bundle; sh., sheath of the bundle; p., process from a tendon cell, t.C, extending into a primary bundle. The entire figure is a portion of a secondary bundle.

Fig. 5x Longitudinal Section of a CalcaNBAN Tendon of Man.

Fig. 53. Tendon Cells from the Tail of A Rat. Stained with Methylene Blue, Intra ViTAM. (Huber.)

The fibrous sheath, vagina fibrosa, which surrounds the tendon, may contain a cavity filled with fluid. Such a tendon sheath is called a mucous sheath, 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 (not a true mucin) which renders it viscid, together with proteid 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 bursae 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 and fasciae 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 derivative of mesenchyma which may develop as sho^Ti in Fig. 54, A. The mesenchymal cells multiply and become crowded

together so .that the intercellular spaces are obliterated. Thus precartilage is formed, consisting of large closely adjacent cells sepa from another by walls staining red with eosin. Precartilage becomes cartilage by the thickening of these exoplasmic walls which become changed chemically so that they stain blue with haematoxylin. The endoplasm may shrink from them so that the cell is seen to occupy a little cavity in the exoplatmic matrix. The cavity is a lacuna and if the matrix around it appears to form a special wall for the lacuna, the wall is called a capsule. The cell is the center of matrix formation, producmg it in concentric layers; and the capsule, being that portion of the matrix nearest the cell, is the part most recently formed. The cells consist of a spongy protoplasm due to vacuoles of fat, and to spaces from which glycogen has been removed. Within a lacuna the cells may divide by mitosis so that there may be four or eight in one capsule. Ordinarily they move apart, by resorbing the adjacent matrix CStohr) or by forming new ground substance which forces them apart (Mall). New exoplasmic walls develop between them, producing characteristic groups and rows of cells such as are shown in the diagram. It has been reasserted that some of the cells undergo a mucoid degeneration and become lost in the matrix. Around the entire cartilage of the adult there is a connective tissue envelope, the perichondrium^ containing undifferentiated cells which by growth and division become cartilage cells. They are added to its surface. The young generations of cartilage cells are therefore at the periphery, and the old are in the center of the cartilage. Between them an interesting series of cytomorphic changes may be seen. The perichondrium contains vessels and nerves. Blood vessels may extend into the cartilage of young embryos, and into cartilages which are being replaced by bone, but ordinarily cartilage is non-vascular, receiving its nutriment by diffusion through the matrix. In surgical operations the preservation of the perichondrium may be of importance, since it can produce new cartilage.

FiG. 54. Diagrams of the Development of Cartilage FROM MF.SENCHYMA.

A, Based upon Studnicka's studies of fish; B, upon Mall's study of mammals. Mes., Mesenchyma ~ cartilage; Cart., cartilage. Pre. Cirt., pre

Fig. 54, B, presents Prof. Mall's idea of the formation of precartilage in mammals, differing from that just described which followed Dr. Studnicka's work on fishes. In B, by the development of fibrils which are exoplasmic structures staining with eosin, the nuclei, and endoplasm become "extruded from the syncytium" and lie in the intercellular spaces. The exoplasm becomes transformed into the matrix of the cartilage. The crowded condition of the nuclei in precartilage makes it difficult of interpretation.

Glycogeny which occurs in cartilage cells, is a carbohydrate resembling starch and known as * 'animal starch." It is soluble in water, and soon after death is converted into glucose. For these reasons it disappears from ordinary sections. Fresh tissues preserved in strong alcohol, and stained with tincture of iodine, exhibit glycogen as brownish red masses, tending to be round, but often not sharply outlined. Glycogen is abundant in embryos in the epithelium of the skin, in liver cells and striated muscles and in cartilage cells. It is found in similar situations in the adult, especially in well-nourished individuals, but is apparently not as abundant relatively as in the embryo. It occurs also in other cells. Its production, like that of fat, may be considered a nutritive rather than a glandular phenomenon.

The matrix of cartilage chemically 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.] The collagen may occur in white fibers which abound in the matrix of that form of cartilage called fibro-carUlage, Elastic fibers predominate in the matrix of elastic cartilage. If, however, on ordinary microscopic examination the matrix appears homogeneous, it denotes a hyaline cartilage. Hyaline, elastic, and fibro-cartilages require special examination.

Fig. 55. The Three Types of Cartilage: A, Hyaline; B, Elastic; C, Fibrous. (Radasch.) t, b, Outer and inner layers of perichondrium ; c, vounR cartilage cells ; d, older cartilage cells ; e, f, capsule; g, lacuna.

Hyaline cartilage macroscoplcally is a pale bluish or pearly translucent substance, firm and elastic. It forms some of the cartilages of the larynx, and those of the trachea and bronchi, the nose, ribs and generally the covering of the joint surfaces, together with the cartilaginous skeleton of the embyro. Its matrix, though apparently homogeneous. Fig. 55, A, is actually fibrillar, as shown by its behavior under polarized light, and by its separation into fibers after artificial digestion. Whether its lacunae are connected with each other by small canals as in bone and in the cartilage of some invertebrates, is very doubtful. Such canals as have been observed are ascribed to shrinkage caused by reagents. Sometimes, as in portions of the laryngeal and costal cartilages, the matrix may develop coarse fibers, neither white nor elastic, which have a luster like asbestos. In old age, and even by the twentieth year in the case of some laryngeal cartilages, lime salts may be deposited in the matrix, first as granules but later combining to form shells enclosing the cartilage cells. Calcified cartilage, together with calcified tendon and other structures, should not, however, be regarded as bone.

Elastic cartilage is a pale yellowish structure containing in its matrix granules, fibers, or networks of elastic material, Fig. 55, B, and Fig. 56. Specific elastic tissue stains are as applicable to cartilage as to connective tissue, and should be used in all cases of doubt as to the nature of the fibers. The elastic elements are found near the cells, but agreement has not been reached as to whether they arise in the matrix or in the exoplasm. Elastic cartilage occurs in the external ear and the auditor}' (Eustachian) tube; also in the epiglottis, the cuneiform and comiculate cartilages, and the vocal process of thearytaenoid cartilages, the last group being parts of the larjoix. Fibrocartilage, Fig. 55, C, appears as a cartilaginous modification of dense connective tissue. A chondro-mucoid matrix forms among the fibers, and the cells which occur singly or in small groups at considerable intervals, are surrounded by capsules. Fibrocartilage is found in the intervertebral ligaments, Fig. 57, in the symphysis pubis, around the mandibular and sternoclavicular joints, at the head of the ulna, in the ligamentum teres of the hip-joint and in other places associated wath joints. Vesicidar supporting tissue is the name given to a tissue found in lower animals, resembling precartilage, and consisting of vesicular cells with firm resistant walls. Such cells may occur singly. They have been described in various tendons, and m the sesamoid bone in the tendon of the human peroneus longus.

Fig. 56. Elastic Cartilage, x 240. I, Portion of a section of the vocal process of an ar>taenoid cartilage of a woman thirty years old ; the elastic substance is in the form of granules. 2 and 3, Portions of sections of the epif^lbttis of a woman sixty vears old ; a fine network of elastic fibers in 2, a denser network in 3. z, Cartilage-cell, nucleus invisible; k, capsule (?).


Bone develops relatively late in embryonic life, after the muscles, nerves, vessels, and many of the organs have been formed. At this time the skeleton consists of hyaline cartilages which correspond with the bones of the adult. Around the cartilages, or in some places quite apart from them, the bone is formed in the following manner:

Fig. 57. From a Horizontal Section OF the Intervertebral Disk ok Man, g, Fibrillar connective tissue; z. cartilagecell (nucleus invisible) ; K, capsule surrounded by calcareous granules. X -240.

Fig. 58. From a Section of the Mandible of a Human Fetus Four Months Old. x

Bone matrix.


Bone cell.


becomine a

bone cell.

In the embryonic connective tissue certain homogeneous strands become apparent, st^ining-de^ly with eosin . Fig. 58. These represent the matrix or ground substanc e o f bone) and are considered either transformations of the exoplasm of the neighboring cells, or as secretions of those cells, or as modifications of connective tissue fibrils. They blend with the connective tissue as shown in the lower part of the figure. (As these strands become oistinct, they are seen to be covered with peculiar cells of mesenchymal origin which tend to form a distinct layer. Since they produce bone they are called osieo' blasts.^ { Blast is a design ation for^a formative cell, and is used in many combinations with a prefix denoting the structure which it produces.)^ (Osteoblasts are Thpy prfi rp]k wifh rounded nucki and ,^]ii^flat to columnar, often being

Fig. 59. Part of a Cross Section of the Shaft of the humerus of a human embryo four months old. X560.

shown in Figs. 58 and 59.

dant protoplasm, varying in shape from

triangular and resting against the strand of bone either by their base or apex. 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 thprp^jv;tenbl?-<;f whjrh hpr/^mPQ fhprpKy ^ fi^f^^ f^l[^

(Fig. 59). Apparently bone cells do not divide, and if they produce matrix, thus becoming more widely s^arated from each other, it is only to a slight extent and in young bones l ^ney are therefore quite i nactlYg- Each bone cell occupies a space in the liyalihe matrix, called as in cartilage, a lacuna,

Fig. 60. Portion of a Cross Section of a Tubular Bone of a Newborn Kitten.

but unlike the lacunae of cartilag e those in bone are connected by numerous delicate canals, the canalictUi. In ordinary specimens the canaliculi are visible only as they enter the lacunae, which are thus made to appear stellatjT ) The matrix around the lacunae resists such acids as destroy the ordinary matrix and thus may be isolated in the form of ** bone corpuscles. The "corpuscles'* correspond with the capsules of cartilage. The bone cells nearly fill the lacunae and send out slender processes into the canaliculi. These may anastomose with the processes of neighboring cells, as can be seen in the embryo, but it is considered doubtful if this condition is retained in the adult. The processes, moreover, are so fine as to be invisible ordinarily, and formeriy their existence was denied.

The strands of bone containing bone cells, and beset with osteoblasts, increase in size and unite so as to enclose areas of embryonic connective tissue containing blood vessels, as shown in the upper part of Fig. 60, and in the diagram, Fig. 61. The connective tissue surrounding the entire network of bone becomes differentiated into a distinct layer, the ^Qtjjjljg^ This includes an outer stratum of ordinary connective tissue (not drawn in the figures), a middle layer of dense fibrous tissue, and an inner cellular layer including the osteoblasts in contact with the outer surface of the bone. Fig. 61 shows the way in which a portion of this inner stratum may be enclosed in the bone matrix. It is about to occur . around the blood vessel,

B. v., and has taken place in the space H. C^ Within such an enclosure the osteoblasts continue to form bone in concentric layers or lamellaey thus gradually reducing the central space until it contains only a few cells and the blood vessels as in H. C^. Such spaces occur abundantly in adult bone, and are called Havef sian canals (in recognition of the anatomist Havers). They are always surrounded by concentric lamellae^ or layers of bone, of which the innermost is the youngest. Between these Haversian systems there are irregular lamellae, called interstitial lamellacy and sometimes a blood vessel runs through them, not surrounded by concentric layers. It is said to occupy a Volkmann^s canal. Transitions from a Volkmann's to an Haversian canal are gradual, and are made not by a change in the canal but by a rearrangement of the surrounding lamellae. Coarse fibers may extend from the periosteum into the mterstitial lamellae, known as Sharpey^s fibers. They consist of more or less calcified bundles of connective tissue fibers, including both white and elastic elements, though chiefly the former. If abundant, the periosteum is most closely adherent to the bone. They are absent from the Haversian systems. Besides the interstitial and concentric lamellae, another set is deposited under the periosteum, parallel with the surface of the bone, the periosteal lamellae [outer circumferential or outer ground lamellae]. If the bone is hollow, having a marrow cavity, similar lamellae may be deposited over the inner surface of the shaft by a formative layer called the endosteum. These lamellae are endosteal lamellae [inner ground or circumferential lamellae, marrow lamellae] and they line the marrow cavity. The four sets of lamellae are shown in Fig. 62.

FiG. 61. Diagram of the Development of Bone. (In part, after Duval.) !., Fibrous layer of periosteum ; o., osteogenic laverof periosteum ; OS., osteoblast ; b. C, bone cell ; B. Vl,, blood vessel ; H. C'm beginning Haversian canal ; H. C*., complete Haversian canal; i. I., interstitial lamellae; c. I., concentric lamellae ; Sh., Sharpey's fibers.

Lamellar bone is compact, differing notably from the spongy network of trabeculae seen in the embryo. Compact bone is found in the outer parts of the long and flat bones and as a thin outer layer in short bones. Spongy bone is found in the interior of long bones, and of flat bones (where it is called diploe), and it constitutes the greater part of short bones and epiphyses. It is due in part to the persistence of the embryonic trabeculae, and in part to the reduction of compact bone to slender spicules through processes of absorption. Scarcely has bone formed before portions of it begin to be resorbed. The osteoblasts disappear locally and in place of them there are large irregular masses of protoplasm containing several separate nu clei. The idea that these structures arise by the fusion of several osteoblasts is not accepted; the nuclei are thought to arise by repeated division within a mass of protoplasm which enlarges but does not divide. The form of giant cell resulting is called an osteoclas t, from its supposed function of destroying bone. The osteoclasts. Fig. 60, are often seen in hollows which they are thought to have excavated in the ground substance, and which are called Howship^s lacunae. Ctbere seems to be no satisfactory\ evidence that the osteoclasts are the cause rather than a product of those ' conditions which lead to the dissolution of bqnp The process of resorption is of the greatest importance, smce it prevents bones from becoming solid and heavy. While new bone is forming on the periosteal surface, old bone is being dissolved, both around the marrow cavity and in the deeper Haversian canals. This process produces most of the spongy bone of the adult.

Fig. 62. From a Cross Section of a Mhtacarpal of Man. X 50 Resorption line at A.

Reviewing the preceding paragraphs, it may be said that bone appears first as strands of ground substance produced by osteoblasts derived from mesenchyma. The osteoblasts may be enclosed by the matrix which they form, thus becommg bone cells. The trabeculae of bone produced in this manner unite in a network, described as spongy bone. By the deposition of new layers or lamellae of bone, which conform with the surfaces on which they are laid down, the spongy bone becomes compact. By resorption of the inner part, the marrow cavity forms and parts of the compact bone become spongy. It remains to consider the substances , and appearances of adult bonej and to describe the manner in which the cartilages are replaced by bone, j

The matrix of bone is at first uncalcified and soft, apparently homogeneous, but actually con*fg'^^-j:v^\-n'gj sisting of cemented fibrils.

It consists chiefly of collagen ^the gelatin-producing substance, and of a mucoid called osseomucoid. Through it there may be distributed fine elastic fibers (said to be lacking in the bones of the vertex of the skull) besides the coarser connective tissue bundles of Sharpey. Soon after this organic matrix is established, calcification begins by the deposition of lime salts either in or between the fibrils. Over 80 % of the inorganic matter is calcium phosphate, Ca3(POj2, the remainder including chlorides, carbonates, fluorides and sulphates of calcium, sodium, potassium, and magnesium. The properties of bone depend largely upon the intimate blending of the organic and inorganic constituents, possibly in chemical combination. The two parts may be separated, however. Acids remove the salts leaving the organic portion as a flexible counterpart of the entire bone. Heat or maceration may be employed to destroy the organic part. Microscopic preparations are made in either way, but usually from decalcified bones. All of the drawings thus far referred to were of such specimens.

Fig. 63. From a Longitudinal Section of a Human Metacarpal. X 30.

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

The cross section of a decalcified long bone of an adult. Fig. 62, shows the perios te um on its outer surface. In favorable specimens it is seen to include an outer vascular, rather loose connective tissue layer, and an iimer dense fibro-elastic layer, in which elastic elements predominate. Into this layer the tendons are inserted, which means that they blend with it and may contribute to the ffbers'penetrating the bone, ^he mhermost cellular layer of the periosteum has become reduced to occasional osteoblasts. These may multiply after an injury; in young individuals, if the periosteum is slit and the shaft of bone shelled out, they may produce a new bone. The cross section further shows the contents of the Haversian canals, which include one or two blood vessels, and a few connective tissue or fat cells. Nerve fibers which are found in the periosteum, where they sometimes terminate in lamellar corpuscles (page 107), have been described as extending into the Haversian canals. They are not easily detected there. Lamellae may be observed as indistinct layers. They are said to be due to the diflferences in direction of the fibrils which they contain, as shown under polarized light. They may also represent differences in texture, from variations in the food supply at the time of their formation. The lacunae may appear either in or between the lameUae. They are nearly filled by the bone cells, which,

Fig. 64. Cross Section of Compact Bone, from the Shaft of the Humerus, showing Three Haversian Systems and Part of a Fourth. {Sharpey, from Bailey's " Text-book of Histology.")

however, are seldom well preserved. The cells are generally flattened, parallel with the lamellae, and are provided with processes extending into the canaliculi. They do not fill them and it is supposed that tissue fluids may circulate through the lacunae and canaliculi. Wandering blood cells are too large to enter them. The Ijrmphatic vessels are limited to the superficial layer of the periosteum. The blood supply of bone is abundant. One or more nutrient arteries enter a bone through its periosteum and break into branches which run in the Haversian canals, thus extending through to the marrow cavity in which they ramify freely. The blood vessels and Haversian systems are parallel with the long axis of the bone, so that they are cut across in cross sections. In longitudinal sections they appear as in Fig. 63. Veins pass back from the marrow, through the Haversian canals, emerging through the periosteum. It will be noticed that in longitudinal sections the lamellar systems are scarcely distinguishable. On the marrow side, the endosteum forms a thin fibrous layer containing occasional osteoblasts and osteoclasts. The marrow will be described with the blood-forming organs.

Fig. 65. From a Dorso-palmar Longitudinal Skction of a Phalanx of the Little Finger of a Fetis Six Months Old. X 60.

Preparations from washed and dried bones show only the calcareous framework. Sections made by sawing show macroscopically an arrangement of the spongy bone in arches and trusses to resist compression. Microscopic sections are made by grinding thin sawed slices until they become translucent, and mounting them so that the lacunae and canaliculi remain full of air. Since the air is refractive it appears black. Thus the canaliculi are clearly demonstrated, as in Fig. 64. They extend from one lacuna to another, connecting the different Haversian systems, and opening into the Haversian canals.




Calcified matrix of cartilage.

The Relation of Bone to Cartilage

Some bones develop quite independently of cartilage. These include, besides the teeth, the so-called membrane bones [intramembranous, connective tissue or secondary bones]. In the midst of the embryonic connective tissue, spicules of bone are formed in the manner already described, and they unite to form a bone. The membrane bones are the bones of the face, and the flat bones of the skull; 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. The remaining bones, being preformed in cartilage, are grouped as cartilage bones [primary bones]. They develop like membrane bones except that the matrix is in part deposited in contact with cartilage in the following manner.

(^ig. 65 shows a longitudinal section of a developing phalanx. On either side of the shaft a strip of bone is seen, formed from undifferentiated cells of mesenchymal origin, situated in the perichondrium. It is called perichondral or periosteal bone, and arises like membrane bone. As a whole, it forms a band encircling the shaft of cartilage. Within it, the cartilage cells have enlarged, and divided so that several cells may be in one lacuna. The lacunae also have increased in size. The matrix in this region stains a deeper blue with haematoxylin than elsewhere, due to the deposition of lime salts within it. On the left a cavity is seen ex

Blood vessel containing corpuscles.

Endochondral bone.

  • â– 

Perichondral bone.


Fig. 66. Fro.m a D(

Perichondral bone.

dorso-pal.mar longitudinal section of a Middle-finger Phalanx of a Human Fetus Four Months Old. X 60.

Hsaline carii^ I -l:i* Kclls in groups).

Hyilinc cariilflge (cells â– .Milarged).

•\ Calcified \ matrix •• / of h>-a* line car tilage.


Fii>|... iKthdral bone

Fig. 67 From a Longitluinai. SKriioN of thr Phai anx of the First Fingrr of a Human Fkiis of Folk Months. » 220.

cavated by the perichondral tissue. Several such buds of tissue will form, invading the cartilage from all sides, and uniting in the center of its shaft. The calcified matrix of cartilage dissolves before their advance, setting free the cartilage cells as the lacunae are broken down. This has occurred in Fig. 66. The tissue which enters the cartilage is a vascular, embryonic connective tissue, containing osteoblasts, and forming the prima ry marrowT) Meanwhile the cartilage has continued to grow, especially in length, and ( the cells in the calcified region have divided so as to form rows. The tr ansverse walls of the Jacun ae are dissolved,Jeaving_deep blue spicules of calcified matrix extending from the ends of the cartilage toward _it§ ' c enter . "Osteoblasts arrange themselves on these spicules and form bone, the matrix of which stains red with eosin. It was formerly thought that

Fig. 68. From a Cross Sfxtion of the Shaft of the Hlmbrls. from a Four Months" HiMAN Fetts. X So.

the cartilage cells set free by the absorption of the walls of the lacunae became osteoblasts, but now they are considered as dying cells without further function. The osteoblasts belong with the invading cells. As seen in Fig. 67, both the perichondral bone on tfiie surface of the cartilage and the endochondral bone forming within it, develop like membrane bone. As the bone grows, the older parts which have formed around the calcified cartilage are resorbed, and in the shafts of adult bones probably no trace of the cartilage remains. In the ear bones, however, calcified cartilage majT be found throughout life. Fig. 68 shows a part of the humerus of a fetus in which the calcified cartilage remains, forming in one place a boundary between endochondral and perichondral bone. The vascular tissue within the shaft becomes marrow, a reticular tissue associated with fat cells, and having developing blood corpuscles in its meshes, to be described later.

• ^^ brief review it may be said that cartilage bones are formed by the deposition of perichondral bone on the outside of a hyaline cartilage, and of endochondral bone upon the lining of excavations within the cartilage. The cartilage is not transformed into bone, although the matrix in part becomes calcified and encased in bone. In the long bones this process of ossification produces a shaft of bone tipped with a mass of

cartilage at either end, Fig. 69, A, B, C. The shaft is the diaphysis; the cartilage ends are epiphyses. At various times after birth, or in the tibia shortly before birth, osteogenic tissue invades the epiphysis and gradually replaces its cartilage by bone. A layer of epiphyseal cartilage between the epiphysis and diaphysis, and a layer of articular cartilage covering the joint surface persist longest. Until adult life the epiphyseal cartilage grows, chiefly toward the diaphysis, and the addition as ^ , „ ^ fast as it forms is replaced by bone. Thus

Fig. 69. Plan of Ossification in a Long Bone, Based upon the Tibia. ^he epiphyseal Cartilage is an essential

Cartilage is drawn in black, and bone is ,.- iit stippled. Art., Articular cartilage; ep., prOVlSlOn for the IcngthwiSe CTOWth of epiphysis ; diaph., diaphysis. ^ o o

bones. The epiphyseal cartilages become entirely calcified at different ages in the various bones, generally from 18 to 22 years, at which time the epiphysis is said to unite with the diaphysis. After that the articular cartilages are all that remain of the original cartilaginous structure which preceded the corresponding bone.

The Joints

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 become a dense connective tissue, either like a fibrous tendon or an elastic ligament, thus forming a syndesmosis; or it may become cartilage, usually of the fibrous type, making a synchondrosis. The sutures are forms of syndesmosis in which the serrate borders of bones are connected by

short fibrous ligaments. The intervertebral ligaments are synchondroses, each consisting of a fibrocartilage which has at its center a soft mucoid substance containing large groups of cartilage cells. This nucleus pulposus is usually interpreted as the remains of the notochord, but some consider that the notochord is entirely absorbed, iliaking the nucleus pulposus an independent formation. The term ligament, it will be noted, is applied to bands of various sorts, fibrous, elastic, or cartilaginous.

In a diarthrosis the mesenchymal tissue between the bones remains comparatively loose in texture and a cleft forms in it, containing tissue fluid. This is the joint cavity, Fig. 70. It is bounded by mesenchymal cells which spread out and form an epithelium, shown in Fig. 71. The epithelium may fuse with the articular cartilage so][that the latter, uncovered by perichondrium, forms a part of the wall of the joint

Fig. 70. Phai.angeal A Four Months'

Joint prom Fetus.

Car., Carlilajce; j. c.» joint cavity; 8. f., stratum (ibrosutn ; s. 8., stratum synoviale.

Fig. 71, An Enlarged Drawing of thk Left Part of the Joint shown in Fig. 70. b.*.. Blood vessel ; car., cartilage ; j. c, joint cavity ; mes. epi., mesenchymal epithelium.

cavity. Articular cartilages are usually hyaline layers from 0.2 mm. to 5 mm. thick, becoming thin at the periphery. The cells near the joint are flattened parallel with the free surface, and some of the deeper of these are said to have lobcd nuclei. The flat cells are succeeded by groups of rounded ones which are described as having protoplasmic processes. In the deepest layers the cells tend to be in rows perpendicular to the joint surface and the matrix is calcified. In Fig. 72 a line is seen separating the calcified from the uncalcified part.

Hyaline cartilage.


(fat cells). Blood vessel.

Fig. 72. Vertical Section throigh the Head of a Metacarpal of an Adult Man. X 50.

Fig. 73. Synovial Vii.i.i with Blood Vessels from a Human Knee Joint, y 50.

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

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. 70). The fibrous layer is specially thickened in various places to form the ligaments of the joint. 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. The synovial layer consists of loose tissue, generally with abundant elastic elements, and in places containing fat cells. It has nerves which may terminate in lamellar corpuscles, numerous blood vessels, and lymphatic vessels which extend close to the epithelium. The epithelium is a smooth, flrlossy layer of connective tissue with parallel fibers and small round or Stellate cells containing large nuclei. They may be spread in a single thin layer, or heaped together, making an epithelium of three or four layers. The synovial membrane may be thrown into coarse folds {plicae) or into slender projections often microscopic {villi). The synovial villi. Fig. 73, are variously shaped but are usually finger-like; they ordinarily contain blood vessels and impart a reddish velvety appearance to the membrane. The large folds of embryonic tissue projecting into the joint, but always covered with the mesenchymal epithelium, may become dense fibrous articular discs such as are interposed in the sternoclavicular and mandibular joints, or they may form the fibrous cartilage-like menisci of the knee joint. Nerves and blood vessels are absent from the discs, menisci, and labra^lenoidalia.

Synovia [synovial fluid] is 94 % water, the remainder being salts, proteids, and mucoid substances, together with fat drops and fragments of cells shed from the membrane.


A tooth consists of three parts, crown, necky 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 foramen apicis dentis. The foramen is shown, but is not labelled, in Fig. 74. The solid portion of the tooth consists of three calcified substances, the dentine or ivory {substantia eburnea)f the enamel {substantia adamantina), and the cement {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.

Fig. 74. longitudinal ground section of a Human Incisor Tooth, x 4.

In the human fetus of about two months the ectoderm covering the jaws is continuous with the entoderm lining the mouth and throat, as shown in Fig. 75, and there is nothing to indicate where they join. Toward the front of the mouth, in either jaw, the epitheUum sends a plate-like prolongation into the underlying mesenchyma. This is called the dental ridge. There is a continuous ridge parallel with the circumference of each jaw, and that it is entirely ectodermal is known from the study of earlier stages when the oral plate is still present. In the diagram, Fig. 76, at A, a part of the ridge in the lower jaw and of the oral epithelium from which it grows, is represented as free from the surrounding mesenchyma. The labial side of the ridge is toward the left and the lingual side toward the right. The ridge later produces a series of inverted cup-shaped enlargements along its labial surface and these become the enamel organs. There is an enamel organ for each of the ten deciduous or temporary teeth in either jaw. Within the inverted cups the mesenchyma becomes very dense, producing in each a dental papilla from which the pulp and dentine are derived. The enamel organ produces the enamel, and perhaps controls the shape of the tooth. The cement is derived from the surrounding mesenchyma.

Three stages in the formation of enamel organs and papillae are shown in Fig. 76. The dental groove in C is a transient depression which is relatively unimportant. In D the enamel organs are connected with the dental ridges by slender necks of epitheHal tissue which subsequently become severed. At about eleven weeks all the papillae and enamel organs of the deciduous teeth have formed. The permanent teeth develop from similar organs and papillae which arise later; the first molars are indicated at five months, and in embryos of six months (30-40 cms.) all of the permanent front teeth may be found. Their enamel organs appear on the labial side of the deep portion of the dental ridge, as shown in Fig. 77, but they are on the inner side of the deciduous teeth. The portion of the dental ridge which is not included in the enamel organs sends irregular projections into the mesenchyma and becomes perforated and detached from the oral epithelium. Its remnants found in the gums at birth have been mistaken for glands. A portion of the ridge extends beyond the necks of the enamel organs for the permanent teeth, and this has been said to indicate the possibility of a third set of teeth, a possibility never realized in mammals. The second and third molars are formed from a dorsal or backward extension of the dental ridge free from the oral epithelium. The second molars appear in a child of six months, and the third or late molars (wisdom teeth) at five years. The latter are not at the extremity of the dental ridge but are on the labial side of it, so that there is a theoretical possibility of fourth molars.

Fig. 75. Part of a sagittal section of a human embryo, to show the position of the dental ridges, D. R.; M., mouth; Md., mandible; My., maxilla; N.. median nasal septum ; P., palate.

Lewis1906 fig076.jpg

Fig. 76. Diagrams showing the Early Development of Three Treth, One of which is shown in vertical section. k. Free border of the dental ridge.

Fig. 77. Teeth from a Human Fetus of 30 CMS. (Modified, from Rose.) E. and E. 0., Enamel organs of a deciduous and of a permanent tooth respectively; O.R., dental ridge; 0. E., oral epithelium; P., papilla.

Enamel Organs and Enamel

The enamel organ is at first a mass of undifferentiated epithelial cells, but soon it becomes divisible into three parts as shown in Fig. 78. The inner enamel cells are applied to the dense mesenchymal papilla; the outer enamel cells, continuous at the rim of the cup with the inner cells, are toward the loose mesenchyma; and the enamel pulp fills the space between the outer and inner layers. The outer enamel cells form a single layer of cuboidal cells, with which some flattened cells of the enamel pulp are in close contact. In later stages the layer appears as a feltwork of flattened elements. It is in close relation with the surrounding vascular mesenchyma, but no blood vessels penetrate it. The enamel pulp is at first a compact mass of ectodermal cells, but by peripheral vacuolization or by the enlargement of intercellular spaces it forms a network considerably resembling mucous connective tissue (Fig. 79). Its slender fibers have been considered as elongated intercellular bridges. The inner enamel cells form a single layer of cylindrical cells separated from the enamel pulp by a cuticular plate, yet connecting with the pulp cells by bridges. Beginning at the summit of the cfown the inner enamel cells produce cuticular basal plates which become long and slender, and later, calcified. They extend from the enamel cells toward the dental papilla. These are the enamel prisms^ and the cells which produce them are called adamantoblasis [ameloblasts]. The formation of enamel prisms spreads from the summit over the sides of the crown and neck, but although the root is enveloped in the enamel organ, no prisms are formed there. The inner enamel cells of the root flatten and by disappearance of the enamel pulp they come in contact with the outer cells. The two layers form the epithelial sheath of the root (Fig. 86).

Fig. 78. From a Cross Skction of thk Upper Jaw of a Human Embryo Five Months Old. x 4.

The adamantoblasts are columnar cells with elongated nuclei toward their outer ends. (Since the enamel organ is an inpocketing of ectodermal epithelium, it is clear that the basal surfaces of the enamel cells are toward the mesenchyma, and the outer surfaces toward the enamel pulp.) Diplosomes have been found near the nuclei. There are terminal bars and a cuticular border at the basal surface, toward which the protoplasm contains granules which blacken with osmic acid. Between the cells there is a cement substance. The long columns (prisms) which grow out from the basal surface of the cells are likewise surrounded by cement substance. The columns at first are not calcified [and are often called Tomes* processes]; they have a honey-comb structure and tend to split into longitudinal fibers. They may connect with one another by winglike expansions. Later both the prisms and the cement substance become calcified, the former increasing in diameter at the expense of the cement. Eventually little (2-5 %) or no organic matter remains in the enamel.

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

Fig. 79. Portion of a Longitcdinal Section of an Incisor Tooth OF A Newborn Kitte.n. y 300.

In this section the young enamel prisms have been pulled out of their spaces in the cement substance.

(The cement of the enamel must not be confused with the cement which covers the root.)

The prisms extend across the enamel from its inner to its outer surface.

As they increase in length the enamel layer broadens. Their course does not remain straight. A vertical median section of the enamel shows in its middle part (Fig. 8i, c) alternating layers of prisms in cross and longitudinal section. At the borders of these layers the prisms are in transition from one layer to the other. At either end the prisms are said to be perpendicular to the enamel surfaces, but in the midst of their course they bend laterally in opposite directions. Thus they reflect hght in such a way as to form alternating hght and dark bands (Schreger's lines) which cross the enamel, and are related to the layers of prisms as shown on the right of Fig. 8i, c. The lines are seen in reflected light. Contour lines (lines of Retzius) cross the prisms obliquely. They are due to pauses in the enamel formation, and in poorly developed teeth especially they are planes along which the enamel may most readily be fractured. Since they often appear brown in sections they have been ascribed to pigment, but it is said that they are air spaces in the cement. They tend to be parallel with the outer surface of the enamel, on which, however, they terminate between the little encircling ridges which may be seen with a hand lens. A few contour lines but no ridges are shown in Fig. 74.

Fig. 81. a, Cross section of enamel prisms (after Sliihr); b, cross sections of enamel prisms (after Smreker): c. Middle part of the enamel from aj^round lonjcitudinal section of a canine tooth (after Kolliker). On the right, seen in reflected light, it shows the light and dark lines of Schreger.

In cross section enamel prisms are shown in Fig. 81. They are from 3 to 6 /^ in diameter, sometimes five or six sided, but often are concave on one surface and convex on the other, being grooved by the pressure of adjoining prisms. They are said to increase in diameter from the inner toward the outer enamel surface. Nodular enlargements have been described, and transverse bands appear in isolated prisms treated with dilute acid.

After birth the tooth pushes out through the tissue of the jaw in which it is embedded, so that its crown becomes exposed. In this process of eruption the outer enamel cells and the enamel pulp are broken through and disappear. That portion of the inner cells which is applied to the enamel prisms remains as an uncalcified but very resistant layer about i n thick, the cuticula dentis [Nasmyth's membrane]. It may be detached by acids which dissolve the enamel but have little efiFect upon the cuticula. The latter, however, yields readily to mechanical erosion, and is. soon worn away. The enamel is the hardest portion of the tooth, surpassing the dentine which is harder than bone.

Dental Papilla and Dentine

The dental papilla has already been described as a dense mass of mesenchyma enclosed and probably moulded by the enamel organ. Its cells branch and anastomose, producing fibrils. The cells next to the inner enamel layer become elongated as shown in Fig. 82, A, and soon constitute a simpte epitheUoid layer as in B. Between them there are groups of fibrils which spread beneath the enamel layer. Calcareous granules are deposited between the fibrils and produce the matrix of the dentine. The elongated cells which are comparable with osteoblasts are called odontoblasts. Unlike the former they never become buried in the matrix, but remain on its inner surface. Long processes extend from the odontoblasts radially through the dentine as seen in the isolated cells in Fig. 83. These processes are lodged in the dental canaliculi and are called dental fibers [Tomes' fibers]. As in bone the canaUculi have an incompletely calcified lining which resists acids. [The canaliculi of the teeth have therefore been described as bounded by Neumann's membrane.] They follow a wavy or spiral course from the outer to the inner surface of the dentine, often being S-shaped as seen in median longitudinal sections.

Fig. 82. Thk Development of Dentine in Pig Embryos. (After v, Korff.) d.. Calcified dentine; e. C. inner enamel cells ; !., fibrous jrround substance of dentine; oil., odontoblasts; p., mesenchymal pulp cells.

Fig. 83. Six odontoblasts with dental fibers, f. p., pulp processes. From the pulp at birth. X 240.

Their diameter increases toward the inner surface where it is from 2 to 4 /^. They branch freely, as shown in Figs. 84 and 85, and terminate blindly or by connecting with neighboring canaliculi. Sometimes they are prolonged into the enamel for a short distance; they may end abruptly as if the terminal part had been destroyed or, in the permanent teeth, the enamel may form knobs invading the dentine. Ordinarily the contact between enamel and dentine is smooth.

The calcification of dentine begins shortly before the formation of enamel and spreads from the crown over the neck and root (Fig. 86). The calcified portion increases in thickness, and contour lines, indicative of stratification, are sometimes seen. Near the enamel there are large irregular spaces of uncalcified matrix which occur in the course of the contour lines if such are apparent. The spaces, which in section suggest bone lacunae, are bounded by rounded masses of calcified dentine, and are therefore called interglobular spaces (Fig. 84). The reason for their persistence is unknown. The interglobular spaces of the root are much smaller and more numerous than in the crown. As seen in Fig. 85 they occur in a layer of dentine not far from its outer surface, and because with low magnification they appear as dots this layer is sometimes named the "granular layer." The compact dentine beyond it is closely joined to the substantia ossea, their canaliculi having been said to communicate. The epithelial sheath which bounded the dentine in early stages becomes reduced to fragments, thus allowing the cement and dentine to unite.

Fig. 84. From a Longitidinal Skction of the Lateral Part of the Crown of a Human Molar Tooth, x 240. 1, Dental canaliculi, some extending into the enamel ; 2, dental crlobules projecting toward the interglobular spaces, 3.

Fig. 85. From a Longitudinal Section of the Root of a Human Molar Tooth. X 240. 1, Dental canaliculi interrupted by a stratum with many small interglobular spaces, 2. 3, bone lacunae and canaliculi.

The pulp of the adult tooth is a very vascular connective tissue of embryonic type. It suggests reticular tissue since its fibrils do not form coarse bundles, and the cell processes remain evident. Elastic elements are absent. The small arteries entering the apical foramen send capillaries close to the odontoblasts, but they do not enter the dentine. There are no lymphatic vessels in the pulp. The medullated dental branches of the alveolar nerves pass through the foramen, lose their sheaths and form a loose plexus beneath the odontoblasts, between which they terminate in free endings. Odontoblasts persist throughout the life of a tooth, and in case of disease or injury they may deposit dentine as a reparative process.

Fic. 86. Longitudinal Section ok a DECiDuors Tooth of a Newborn Dog. X 42. The white spaces between the inner enamel cells and the enamel are artificial, and due to shrinkage.


The papilla and enamel organ together are surrounded by loose mesenchyma extending to the oral epithelium and to the bone trabeculae of the developing jaws, as shown in Fig. 87. The portion of mesenchyma between the trabeculae and the teeth forms the so-called dental sacs. Toward the enamel organ the sac is a vascular and very loose tissue (Fig. 86) which may form elevations between projections of the outer enamel layer. The peripheral part of the sac is much denser. After birth,

Cross section of the orbicularis oris muscle.

Fig. 87. Vertical Section through the Lip and Jaw of a Human Fetus of Six and a Half Months. X 9.

but before the eruption of the teeth, the sac surrounding the root produces the cement or substantia ossea. This is a layer of bone, containing typical lacunae and canaliculi and penetrated by many uncalcified connective tissue fibers (Sharpey's fibers). These may be so numerous as to suggest the columnar appearance of enamel. Their direction is generally radial. Lamellae in the cement are parallel with the surface of the root. Haversian canals are absent except in the outer part of the cement of old teeth.

As the footh grows and fills the alveolar socket in the jaw bone, the dental sac is reduced to a vascular fibrous layer, continuous with the connective tissue of the gums at the neck of the tooth. Elastic fibers are absent. It is a single layer serving as the periosteum of the cement on one side and of the alveolus on the other and being intimately joined to both bones by Sharpey's fibers. It is named the alveolar periosteum [peridental membrane]. Its numerous blood vessels are branches of those which enter the apical foramen together with vessels from the gums and perhaps from the mandible and maxilla. Its nerve endings are the terminations of branches from the dental and alveolar nerves. Lymphoid tissue has been found in the gums, but apparently it does not extend into the alveolar periosteum.

Muscle Tissue

Contractility is a fundamental property of protoplasm. Muscle cells are those in which the contractile function has become predominant. They are elongated cells containing fibrils parallel with their long axes. By the shortening of these fibrillated cells muscular action results. Embryologically muscles arise either from mesenchyma or from epithelium. Mesenchyma produces two types of muscle, smooth (non-striated, involuntary) and cardiac (the striated, involuntary muscle of the heart). Mesodermal epithehum produces one type, the striated voluntary skeletal muscles, ordinarily called striated. In the invertebrates ectodermal and entodermal epithelia also produce muscle cells. In mammals the muscle fibers of the sweat glands are generally recognized as ectodermal, and some in the iris have been described as such; entodermal muscles have not been observed.

The three principal classes of muscles, smooth, cardiac, and striated, may be described in turn.

Smooth Muscle

Smooth muscle develops around the large lymphatic and bloodvessels; around the intestinal canal, including the principal gland ducts opening into it and the large respiratory tubes'; also around the bladder and ureters, the uterus and ducts of the genital system; and, finally, in connection with the hairs, in the capsule of the spleen, and in other minor places. In general terms, it form s the musculature of the viscera. >

The development of smooth muscle may be studied in a cross section of an i8nmi. pig embryo (Fig. 88). The stratified entodermal epithelium

Fig. 88 From a Cross Section OF THE Oesophagus of an i8 MM. Pig.

epi.. Epithelium; b. m., basement membrane; c. t., connective tissue; c. m., circular smooth muscle cut leng:thwise ; n. C, nerve cells; I. m.,lonsritudinal smooth muscle cut across.

which lines the oesophagus, a part of which is shown in the figure, is seen to be surrounded by mesenchymal tissue in which the smooth muscle cells are being differentiated. There is a layer, c. m., in which the cells have become spindle-shaped, and since they are parallel and close together, they form a band encircling the oesophagus. Outside of this there is a broader layer of elongated cells, 1. m., all running lengthwise of the oesophagus and therefore cut across in this section. This layer of longitudinal muscle passes into mesenchymal tissue on the outside. (The figure illustrates that smooth muscle cells are^elongated^ mesenchymal cells; gener ally parallel and arranged in layers. In the embryonic stage they are con FiG. 89. Smooth Musci.b Fibers from the Small Intestinr «o/*fo/1 Kv T\rr\f/\_

OF A Frog. X 240. neciea oy proio plasmic processeslN Smooth muscle cells in the adult may occur singly or in the form of interlacing networks. Generally they are in layers and so closely packed that separate cells are hard to follow. Moreover they often extend beyond the planes of the section so that only portions of them are included in the specimen examined. If a piece of fresh tissue is treated with a 35 % aqueous solution of potassium hydrate or 20 % nitric acid, the cells may be shaken apart, and appear as in Fig. 89. They vary in length from 0.02 mm. in some blood vessels to 0.5 mm. in the pregnant uterus; in the intestine they are said to be about 0.2 mm. Their width ranges around 0.005 mm. (5 fJL). They are fusiform or cylindrical, rarely being branched as has been recorded for muscle cells in the bladder, the ductus deferens, and the aorta (Fig. 156, p. 131).

(The nucleus , situated near the center of the cell, is cyhndrical^ith its chromatin in a network and in ^^^smoo^h muLcle masses lining the nuclear membrane. In favorable prep- ART*'F!ifY ^ofa dog^ arations it has been observed to contain several nucleoli, and a diplosome has been found just outside of its longitudinal border. When the muscle cell contracts the nucleus shortens and may be bent or spirally twisted, Fig. 90. (Such nuclei have been interpreted as distortions of resting nuclei caused by the contraction of neighboring cells.)

The protoplasm of the smooth muscle cells early produces coarse fibrils called border fibrils [myoglia], since they tend to be at the periphery of the cell. They are said to extend from cell to cell, which is made possible by the syncytial arrangement of mesenchyma. In one interesting but unique instance, the fibrils from the mesentery of a salamander showed

End of a muscle fiber. Nerve cell.

Fig. 91, Apparent Intercellular Bridges of Smooth Muscle Fibers. A, Transverse section of the intestine of a rabbit. B, Longitudinal section of the intestine of a guinea pig. X 420.

alternating light and dark bands, very distinct in photographs. The fibrik of cardiac and striated muscles are always banded in this way. Some investigators consider that the border fibrils are the contractile elements. Others hold that by their elasticity they cause the muscle cells to elongate after contraction, thus being an obstacle to contraction. The elongation of the relaxed muscles, either in the blood vessels or in the intestinal wall, may be accomplished by the pressure of the contents of these organs, or by the elastic connective tissue which is outside of the muscle cells. In the endoplasm of smooth muscle cells, and thus surrounded by the border fibrils, minute inner fibrils have been described and said to be contractile. Among them is the unaltered protoplasm. Where the fibrils diverge to pass around the nucleus, that is, at the ends of the nucleus, the granular protoplasm is most readily distinguishable. In the intestine it has been observed to contain pigment. Surrounding the smooth muscle cells there is probably a delicate cell membrane, but the nature of the structures observed is still under discussion. The cell membrane of a muscle cell is called a sarcolemma; its protoplasm is named sarco plasm; and the entire cell is called a muscle fiber. Fibril is applied to the filaments within the fibers.

(Smooth muscle cells are bound together so that they may act in unison. They may be joined end to end by the border fibrils. ) Protoplasmic bridges have been described between them (Fig. 91).

Fig. q2. FiBRors TissrK in Rkiationwiih S.mooth Muscle Fibeks. from the Bladder of a Pike. (After Prenanl.)

C, Connective tissue network ; n., p., f., nucleus, eraiiular protoplasm, and fibrillar protoplasm uf a muscle cell.

They are certainly closely invested by connective tissue membranes or networks (Fig. 92), consisting of white and elastic elements and extending from cell to cell. These may be formed from the protoplasmic processes of the mesenchymal muscle cells, or from distinct interspersed connective tissue cells. Tissue spaces exist in this network between the muscle fibers. The loose muscular coat of the blood vessels in the umbilical cord is a particularly favorable place for the study of fibrous tissue in relation to smooth muscle.

(^ ordinary sections the student should recognize smooth muscle by the parallel arrangement of its cells, with which the nuclei correspond, and by the protoplasmic appearance of muscle substance as compared with fibrous connective tissue?) In doubtful cases Mallory's connective tissue stain may be used, making the muscle substance red and the white fiber blue. In cross section smooth muscle appears as in Fig. 93. Since the cells taper the sections near their ends are smaller than the others. Only those cut near their centers show nuclei. Between groups of muscle V , . cells there are generally bands of

. . IhY^xyv^^^^TiT^Tri connective tissue containing lym Conneclive tissue ^JlU.^djrCjW °

septum. ^'ciC^ phatic and blood vessels, and nerves

(ji|A?^^n^ which terminate in contact with the

Smooth muscle fibers) ^2ij!ia>t?VG>t^^ ^ells in a manner to be considered

and nuclei in cross V ~\JIII^p^ \^i^^'-^ i >-*^> i m •

section. j _i4C3Hb>»^^^ later. (In describmg smooth muscle

Fig. 93.-SECT.0N OF TH« CIRCULAR MUSCLE the student should always record

Coat of the Intestine, x 560. whether it is ckcukr, longitudinal,

or oblique in relation to the organ of which it forms a parO This relation is independent of the plane in which the organ has been sectioned, and in many small sections it cannot be determined from observation. He should add the way in which the fibers are cut, whether lengthwise or across, and this depends entirely on the way in which the sections happened to be made. It can always be observed in the specimen. Thus in Fig. 88 the student should observe an inner layer of muscle fibers cut lengthwise and an outer layer cut across. If he knows that the inner layer of intestinal muscles is generally circular, and the outer layer is longitudinal, he infers that Fig. 88 is from a cross section of the oesophagus. If the oesophagus had been split, the inner circular fibers would have been cut across and the outer ones cut lengthwise. Being told that Fig. 93 represents the circular layer of muscle, he can state whether it is from a transverse or a longitudinal section of the intestine.

Cardiac Muscle

Cardiac muscle begins as a mesenchyma with very broad protoplasmic connections between its cells. This syn cytial c ondition is retained in the adult, cardiac muscle being a network of broad protoplasmic bands, in

and near the centers of which nuclei are situated at irregular intervals

liberal union. (Fig- 94) • The intcrc^Uular spaces

are reduced to clefts occupied by a

small am ^^jJlt Pf rny^r^t^n\\xrt^ ^^'^^^r

which is either a part of the original

Nurle»i«i of Nucleus of Intercalated a muscle a connective disc,

fiber. tissue cell.

Fig. 04 From a LoNr.iTrniNAL Skction of \ Papillary Mrsci.K of thk Human Heart. X ^f-o

Fig. 95. Part of the Miscular Syncytium FROM THK Heart of a Duck Embryo of 3 Days. {M. Hfidrnhatn, from McMurrich's " Embryolojfy. ")

mesenchjTTia or a later ingrowth accompanying the blood vessels.^

^ht protoplasm of cardiac muscle contains longitudinal fibrils/) Early in development they are few in number and sityated near the periphery of the bands of protoplasm. <^hey %-^^f

extend for considerable distances through the syncytium regardless of cell areas (Fig. 95)?) Their ^rigin is a subject for speculation. It has been suggested (i) that they are bundles of ultra-microscopic molecular fibrils; (2) that they develop by the coalescence of granules in the hyaloplasm between the reticular network of protoplasm; and (3) that they are parts of this network, supposed to be retractile, which is irregularly arranged in ordinary cells but which in muscle cells has acquired rectilinear meshes. At first homogeneous, they soon become marked by alternating light and dark bands. They increase in number by longitudinal splitting.


oi-- A Frog. X 240. f., F'ibrillae ; k., nucleus.

The protoplasm

becomes nearly full of these fibrils, so arranged that their light and dark bands appear to form continuous stripes across the muscle fiber (Fig. 94). ^hat the transverse striations are optical effects is shown by the readiness with which they may be broken up by the separation of the longitudinal fibrils (Fig. 96)!) The dark bands stain more deeply than the light ones, / which perhaps is not due to chemical differences but is because they are ' denser, containing less water. In polarized light the dark bands are ["doubly refractive" or anisotropic and the hght ones are "singly refractive" or isotropic.

The finer structure of the fibrils such as occur both in cardiac and in the skeletal muscles, is shown in the diagram. Fig. 97. The light band is bisected by a slender dark one said to be continuous from one side of the fiber to the other, thus connecting the fibrils with one another. Since such a transverse membrane is not present from the first it has been suggested that it forms by lateral outgrowths of the fibrils. It is named the ground membrane of^Krause, and is always designated by the letter Z. The light band is /. The large dark band seen with ordinary lenses

Fic. 97. Diagram of Muscle Striations. The fibrils consist of alternating dark bands, q, and light bands, j. i is traversed by the ground raeoibrane z, and q by the median membrane m. In the right of the three muscle segments shown in the figure the bands, n, have been drawn. (The portion of j between n and z is designated a.)

is called Q. It grows lighter toward its middle part where it is sometimes crossed by the median membrane of Heidenhain, M. This is thought to be similar to the ground membrane Z, but more delicate. The light portion of Q through which it passes is designated H. In some highly developed muscles of insects a dark band N is found in J. It is of uncertain nature. The fiber as a whole is divided by the ground membranes which cross it, into a series of similar compartments called muscle segments ( sarcomeres) . Additional sarcomeres may be formed at the ends of muscle fibers; it has not been found that the median membrane can become a ground membrane, thus producing two segments from one.

(The contraction of muscles corresponds in its rate with the complexity of the striae) Thus smooth muscles which are non-striated contract slowly. TEe more rapidly acting muscles of some invertebrates have banded fibrils but lack the orderly arrangement which produces transverse striations. The highest development of striated structure is perhaps in the wing muscles of insects which contract with great rapidity, is the muscle cell contracts it broadens, and shortens, even to one tenth of its length when at rest (Prenant). The ground membranes approach one another (Fig. qSJT) It has been said that by a transfer of light substance to the dark the staining reactions are reversed, but this has been denied.' The retreat of the protoplasm into capillary spaces between the dark fibrils has been described. The process is known to be most complex, involving physical (electrical) and chemical changes which are but imperfectly expressed in the histological pictures. With prolonged activity g the muscle nuclei are said to shrink

w| and to stain less deeply.

â– p In ordinary specimens of cardiac

^^ c muscles the student will observe only

the alternating light and dark bands, with possibly the ground membrane Z. On changing the focus the dark bands may appear light and vice versa, but in the proper focus for adjacent nuclei and connective tissue,

Fig. 98. Fibrils from the Wing Miscles OF A Wasp. (Schafer.)

A, Contracted ; B, stretched ; C. uncontracted. The dark bands are bisected by the li^ht stripes { H ) , but they do not show the median . membranes (M).


Cardiac Muscle, Stained with Thiazin Red and Toluidin Blue. The Ground Membranes are Lettered z. (Hcidcnhain.)

the bands appear as has been described. At irregular intervals, in cardiac muscle only, transverse lines of another sort may be found, called inlercalated discs and formerly known as cement lines.- /('ft I » rut r^"^"Intercaiated discs are seen in Fig. 94, and as pictured by Prof. Heidenhain, in Fig. 99. He describes them as deeply staining plates ahnost invariably not as wide as a muscle segment. The segment in the human heart is 2 /i, whereas the intercalated discs vary from i to 1.7 /^. A disc may extend straight across a fiber, or it may be interrupted so as to form a succession of steps, usually from two to four. The discs are always

X Capillaries.

connected with ground membranes. It may be said that here and there within the cardiac muscle two successive ground membranes are closer together than usual and the fibrils in crossing such an interval become expanded and more stainable, thus making an intercalated disc. The discs have been variously interpreted, for example, as locally contracted segments; as lines where the fibrils are inserted and upon which they may pull in contracting; or as places where the fibrils may grow to form ngw segments, being comparable with the unhanded embryonic fibrils, ^^e older idea that they are cell boundaries, either cement lines, or protoplasmic

bridges, is supported by ~ \ ^-ff'^^*^^^ ^^^ tendency of heart

musj je to rupture alonp their course^ They mark off irregular spaces, however, some containing more than one nucleus, and others non- nucleated. Intercalated discs should be distinguished from the cut edges of fiber, made where a branch of the syncytium extending toward the observer, passed out of the plane of section.

^h e nuclei of cardiac ^ musc!e"are round or oval and are found near the central axes of the fibers^ ^s the fibrils spread out to pass around them, often a considerable quantity of granular p rotoplasm may be seen, containing fat droplets and pigment granule s which increase with ag^ A delicate membrane (sarcolemma) has been described as surrounding the cardiac fibers, and in it the ground and median membranes are said to terminate. Some of the clefts in cardiac muscle are protoplasmic (sarcoplasmic) intervals between bundles of fibrils. Others, bounded by the sarcolemma, are spaces which contain capillary vessels closely applied to the muscle. Probably always a little connective tissue intervenes between the vessel and sarcolemma. The connective tissue, which is more abundant toward the surfaces of the heart, contains tissue spaces and the nerves

Elulo- Elaslic Nucleus Cross Nucleus helium. fibers. of a sections of a connective of muscle tis^iue muscle fiber, cell. fibers.

Nuclei ot connec live tissue cells

Fig, loo. From a Cross Section of a Papillary Miscle OF THE Human Heart. X 3^«.

which terminate in contact with the cardiac muscle fibers. Lymphatic vesseb are found in the larger layers and bands of connective tissue, but they end before penetrating between the separate fibers.

Although the cardiac muscle fibers form a network, they are in layers, ^ each having one general direction. . Since the predominant direction varies in different parts of a single section it is possible to find places where | the fibers are mostly cut lengthwise as in Fig. 94, and others where they I are cut across (Fig. 100). Here transverse bands and intercalated discs \ cannot be seen. The nuclei surrounded by some protoplasm are near( the centers of the fibers. The fibrils cut across appear as dots which shift j about but do not disappear on focusing, since even in thin sections they : are not granules but short perpendicular rods. They are arranged in radiating lines, or in clumps known as muscle columns, ^los e to the inner lining of the heart the muscle fibers may be ipiperfectlv developed, (^p ntaining only a peripheral rinp of fibr ils^ These fibers (of Purkinje ] ) f'^^ are abundant in the sheep but are infrequent in ma n.3 ' \.J^

Smooth muscles are slender mesenchymal cells containing contractile fibrils which are not banded. The cells, surrounded by a fibro-elastic 1 (29 f^ network, are gen erally closely associated in layers. If the border fibrils actually pass from cell to cell, as has been said, then smooth muscle, like other muscle, is s)ntic)rtial in nature.

Cardiac muscle is a syncytium of mesenchymal origin, consisting of broad approximately parallel branches. It contains banded contractile f fibrils not limited by cell areas. It is distinguished from smooth muscle by its cross striations and by the width of its fibers; and from striated j (voluntary) muscle by its mesenchymal origin, the branching of i t s syncy tjum, the central position of its n uclei, and the possession of intercalate discs. ~ "

Striated Muscle

Striated muscle, as the term is ordinarily used, does not include the striated cardiac muscle, but only the striated muscle which develops from Qie epithelium of the mesodermic segments [protovertebrae]. The segments form a series of paired masses of cells found on either side of the medullary tube. They have been briefly described on page 22. At first they are epithelial structures bounding a part of the coelom or body cavity. Later they lose their connection with the coelom (Fig. 21) and become rounded masses of cells, each mass enclosing a cavity. From the median side of the segment, near its ventral border, a stream of mesenchymal cells is

given off, which surrounds the notochord and produces the vertebral cartilages and intervertebral discs. It also extends around the medullary tube. This stream of cells is called the sclerotome. The rest of the segment becomes flattened and plate like, by the approximation of its lateral and medial walls. Thus the central -cavity is obliterated. Fig. loi, i, shows a cross section of such a segment. Its medial layer is called the muscle plate or myotome. Here the cells multiply rapidly by mitosis and become elongated lengthwise of the embryo. They are called myoblasts and become the striated muscle cells. The lateral layer of the segment, named the cutis plate or dermatome, was supposed to form only mesen chyma which became the deeper part of the skin. It also forms striated muscles, however, and in the pig it is said to be concerned only with muscle formation. The elongated cells of the myotome become separated from one another by mesenchyma, containing blood vessels. Thus the myotome is subdivided into layers and groups of cells which shift about in various directions to become the skeletal muscles of the adult. The mesenchyma around them forms fascia and tendon, and connects with the periosteum which is often derived from the sclerotome. In the adult some of the myotomes remain quite clearly defined; thus the muscles of each intercostal space are derived from a single mesodermic segment, the ribs having developed between them. In the abdominal muscles several segments have fused. The muscles of the limbs are supposed to arise from myoblasts which have migrated into them from the myotomes of the adjacent body wall. Apparently they come directly from mesenchyma. (^11 the striated skeletal muscles, however, are believed to come directly or'indirectly from the epithelium of the mesodermic segments^

In cross section the myoblasts are of rounded outline (Fig. 102), bounded by a delicate cell membrane or sarcolemma. This membrane is in close relation with processes from the adjacent mesenchymal cells and it has been said that the well defined sarcolemma of the adult is essentially a product of such cells. The myoblasts consist of granular protoplasm (sarcoplasm) with coarse fibrils near the periphery and nuclei in the central part. In a given cross section the nuclei of many of the

Fic. lor. Three Mksodbrmic Segments from Amphibian (SiRKDON) Embryos, of Successively Older Stai;ks. (Diaj{:ranis after Mauier.)

m., Muscle plate; c, cutis plate; the former is resolved into muscle fibers, m. f., the latter in part into muscle fibers and in part into mesenchyma, met.

myoblasts will not be included. In becoming muscle fibers the myoblasts increase to a diameter of from 10 to 100 //. (The fibrils multiply by longitudinal splitting so as to form groups of fibrils, or muscle columns, which in cross section are called Cohnhei m^ are^ Fig. 103 shows four adult muscle fibers cut across, in all of. which Cohnheim*s areas are distinct. Often such areas are not distinguishable, however, and when present they may appear as though due to shrinkage. Between the areas is the sarcoplasm which may show '^interstitial granules" of fat or lecithin. (The ^/ nuclei of striated muscle fibers, not seen in the figure, are usually flattened I and dose to the sarcolemmaT^ The fibers just described belong to the pale or white type. In the dark or red form the protoplasm is more abundant and granular, the diameter is less, the fibrils fewer, and the nuclei may be central or imbedded among the fibrils. Clearly this type

Fig. 102. Cross Section op Myoblasts


iS MM. Pig. flits.. Mesenchymal cdl ; f.. fibril ; n., nucleus ; t., sarcolcmma, of a myoblast.

Connective tissue.

Fig. 103. Cross Skction of Four Muscle Fibers OF the Human Vocal Muscle, x 590.

is intermediate between the myoblast and the pale form. The dark fibers contract more slowly than the light ones, but are less easily fatigued. They are found in the ocular muscles and in those of mastication and of respiration. In some single muscles both types with intermediate forms may be observed. Ordinarily striated muscle is of the pale type.

The mesenchyma surrounding the myoblasts becomes connective tissue. It envelops each fiber as shown in Fig. 103, and in progressively wider bands it surrounds small bundles of fibers, large groups of these bundles, and the entire muscle as shown in Fig. 104. The connective tissue layer which covers the whole muscle is the external perimysium; its prolongations into the muscle form the internal perimysium. It contains fine longitudinal elastic elements and sometimes fat, chiefly in the outer layer. Elastic substance is particularly abundant in the diaphragm. Lymphatic and blood vessels and nerves extend through the perimysium. The lymphatic vessels end before reaching its smaller

Muscle spindle.

Cross section of nerve.

Connective liisuc.

Muscle fiber. Connective tissue.

'â– ' r^

Fig. 104. From a Cross Section of thb Omohyoid Muscle of Man. X 60.

subdivisions. Capillary blood vessels are found between the individual fibers, with which they tend to be parallel. The nerves, chiefly motor, terminate on the fibers. Sensory nerves are associated with the muscle

spindles (Figs. 104 and 105) which in cross section are small groups of slender fibers, containing many nuclei. (For further description see page 103.)

Since adult striated muscle fibers attain a length of from 50 to 120 millimeters, complete longitudinal sections of them are seldom seen, (^single fiber contains very many nuclei (scores or perhaps hundreds), gener ally flattened oval structures just inside the sarcolemma. "" Sometimes the nuclear membrane is indented by the adjacent fibrils.' ""The sarcolemma is most clearly seen

Cross section of nerve.

Fig. 105.

Muscle fil»crs Nucleus Nucleus of Ihe of the of the sarcolemma.

spindle. perimysium. Thf. Mf-scLK Sj'indi.f. shown in Fig. 104. X 240.

Fig. 106. SiRiATKo MiscLK Fiber of Frog, Tkaskd Apart in Water, Being Torn at x, and showing


in fresh fibers within which the fibrils have been ruptured and have dra^\Ti away from the membrane (Fig. 106). It resists acetic acid and has been considered elastic. These fibers arise from myoblasts which at first have single nuclei within their central portions. As the cells elongate their nuclei divide rapidly, at first by mitosis and later, it is said, by amitosis. It is generally denied that the adult fibers are due to a fusion of myoblasts. The first fibrils are homogeneous structures at the periphery of the cells. It has been observed that the activity of certain muscles in living embryos begins at the time that their fibrils appear. As the fibrils multiply and fill the cell the nuclei migrate toward the sarcolemma. The striations which have been described under cardiac muscle, are most perfectly developed in the voluntary muscles. All that can ordinarily be seen of them, however, is shown in Fig. 107, namely, the alternating dark and light bands, the latter bisected by the ground membrane. Sometimes, though rarely, as a result of treatment with alcohol the muscle fiber breaks into transverse discs, called sarcous dements^ each having the thickness of a muscle segment. These elements are single layers of cuboidal blocks, one for every longitudinal fibril, and these blocks may separate from one another. Neither the elements nor their small pieces are now considered significant.

The extremities of the muscle fibers are rounded or conical, the end toward the tendon being more obtuse than the other. Near the tendon the fiber contains many nuclei both peripheral and deeply placed. They divide by amitosis and provide for lengthwise growth of the fiber. Connection with the tendon is established by the perimysium which is continuous with the tissue of the tendon. The sarcolemma ends with the muscle substance. Such striated muscle fibers as are inserted in the skin or mucous membranes may be pointed or branched (Fig. 108). Their perimysium is prolonged in the form of elastic fibers which blend with the surrounding connective tissue.

Fig. 107. Part of a LongiTUDiAAL View of a Human Striated Muscle Fiber.

a., Anisolropic ; I.,

band; k., nucleus; ground membrane

X 5^




Fk;. loS. Branched Striated Mrsri.K Fiber from THE of a Frog.

The diameter of muscle fibers is greater in large animals than in small ones; it is increased by functional activity; and varies with the general nutrition so that the caliber may become perhaps trebled. It is doubtful, however, if any new striated muscle fibers develop in the adult. Some have said that they are constantly being worn out and that new ones form to take their places, developing from latent myoblasts. It seems to be generally considered that the formation of new fibers ceases in the embryo; muscle destroyed by injury is not restored in the higher animals. The origin of muscle fibers by division of those already formed, rather than by the development from myoblasts, is also generally denied.

Striated muscle occurs not only in the mus cles of the limbs and body -w^m but^lso in the ocujar and ear muscles, the diaphragm, the to ngue, pharynx, larynx and upper half of the oesophagus, and in parts of the rectum and genital organs.

Nerve Tissue

Irritability and conductivity have already been mentioned as fundamental properties of protoplasm. Response to particular irritants becomes the chief function of certain cells. Thus some cells in the eye are differentiated to react to light; some in the ear respond to sound; the taste cells of the ton gue and olfactory cells in the nose are affected by solutions tactile cells are Influenced by pressure, an3 muscle cells contract at the stimulus of the nervous impulse. The effects of irritation may be conveyed from one part of the cell 'to another through its power of conduction. Thus when a muscle fiber is stimulated at one point, a wave of contraction may be transmitted along its whole extent; or when an olfactory cell is stimulated, the effects may be conveyed through a long fiber-like basal prolongation toward the brain. For the purpose of connecting these particularly irritable cells there exists a specially modified median longitudinal tract of ectoderm, the nervous system. Some of its cells send out slender prolongations, know as nerve fibers^ to meet the taste cells, the auditory cells, the processes of the nasal cells, the cells of the muscle spindles or the epithelial cells of the skin, and to branch in contact with them. The effects of stimulating the various irritable cells enumerated, are conducted along these nerve fibers back to the central nervous tract. Such fibers as convey peripheral stimuli to the central system are called afjereni or sensory fibers; they are the outgrowths of sensory cells. Another set of nerve fibers grows out from the central tract and branches in contact with muscle cells, smooth or striated. Since they transmit stimuli which cause the muscles to contract ihcy eLvecaMtd motor fibers, and the cells of which they are a part are the motor cells. The effererU fibers, or those which bear impulses from the central tract to the periphery, include the motor fibers, and also some which pass to the epithelium of glands to control their activity. Besides the afferent sensory and the efferent motor fibers there is a third set of cnmmissurnl c.pRr anH fiw connect the other tw o. Senspry and mnfn^ c^^ may rnnnprf without the intervention of commissural cells, thus j)roviding a path for the simplest form of unconscious reflex jictifln but often one .or more commissural . , cells are interposed and the brain consists essentially of these cells. As ; the nervous impulse is transferred from cell to cell, being further removed from the primary stimulus, it is suggested that it becomes "more subjective^and personal.

( The nervous system, then, is a median longitudinal tract of ectodermal , cells, divisible into afferent (sensory), efferent (motor), and commissural cells. The sensory and motor cells send out processes or fibers, which in bundles called nerves extend through the mesenchymal tissue to all parts of the body. The central tract is called the central nervous system and consists of the brain and spinal cord. The nerves constitute the peripheral nervous system. Associated with the nerves there are clumps of nucleated bodies of nerve cells, known as ganglia. The affer ent aad efferent fibers to the viscera and blood vessels, together with numerous gan^fi[li a,"constitute tiie"sympathetic nervous system. The nervous system, j therefore, Is composed of central, peripheral, and sympathetic portions^)!

Development of Nerve Tissue

The Central Tract. The ectoderm in an early stage forms a flat layer covermg the eml5ryo (Fig. 109 A). Along the axial line and extending on either side of it, the ectoderm thickens to form the medullary plate. The plate becomes depressed so as to make a longitudinal groove, the medullary groove [or neural groove] (Fig. 109 B). The dorsal edges of the groove come together and fuse, transforming it into the medullary [or neural] tube (Fig. 109 C). Thus the tube becomes separated from the general layer of ectoderm which is to form the epidermis. This medullary tube is the central nervous system. In its anterior part the cavity is trans- 1 formed into a series of connected dilated spaces or ventricles, and its ' walls become very thick, thus forming the brain. The posterior part , makes the spinal cord; its walls are less extensively but more uniformly thickened than those of the brain, and its cavity remains small, becoming the central c anal. This canal is continuous with the ventricles of the brain and a line of division between the spinal cord and brain must be arbitrarily drawn. The relations of the medullary tube to other structures in the embryo have been shown in Figs. 19-21, p. 19-22.

Fig. 109. The Development of the Nervous System as seen in Cross Sections of Rabbit Embryos: A, 7^4 Days; B, 8^ Days; C, 9 Days; D, ioJ4 Days; E, 14 Days. C. C, Central cavity ; d. r., dorsal root ; d. ra., dorsal ramus ; ep.. ependymal layer * g. c, j^nglion cells ; g. I., gray layer ; m. g., medullary groove ; m. t., medullary tube ; 0. b., oval bundle ; t. g., sympathetic ganglion ; $p. g., spinal ganglion ; t. ra., sympathetic ramus ; v. r., ventral root ; v. ra., ventral ramus ; w. I., white layer.

The Spinal Ganglia. At about the time when the medullary tube separates from the epidermal ectoderm, some cells which are detached from its median dorsal portion pass down on either side of the tube, as shown in Fig. 109 C and D. Through mitotic division these cells accumulate in paired masses corresponding in number with the segments of the body. They are 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 sides of the cell (Fig. 1 10). With further growth the nucleated cell body passes to one side of its prolongations, with which it remains connected by a slender stalk. These T-shaped cells are characteristic of the spinal ganglia. The fibers which grow toward the medullary tube enter its outer part and fork, sending one branch toward the brain and the other down the cord. There are many of these parallel fibers extending toward the brain so that they form distinct bundles, one on either side of the cord, known as oval bundles (Fig. 109, E). Since they receive acccs

Fig. no. Spinal GAsrji.ioN Ckli.s. the Ripoi AR Forms irom a 6 Day Chick Embryo.

sions of fibers from every spinal ganglion, they enlarge as they approach the brain. The fibers of the oval bundle branch freely at their termination and also give off collateral branches along their course, which enter the deep substance of the cord. The perighejaLfib^FS from the spinal ganglia elongate through the mesenchyma, and terminate in branches applied to cells in. the. skin or muscle spindles, in ways to be described presently. The fibers of the spinal ganglia are essentially afferent or sensory, and they proceed from sensory cells.

The Ventral Roots. The efferent, motor fibers arise chiefly from cells, the bodies of which remain within the central nervous system. Each of these cells sends out one long process called a neuraxon (axone). The neuraxons of the motor cells leave the spinal cord, near its ventral surface, in bundles which are segmentally arranged so that they correspond with the spinal ganglia. A bimdle of motor fibers joins a bundle of peripheral fibers from a spinal ganglion to form a spinal nerve . Every spmal 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 motor fibers terminate in contact with muscle cells. / Soon after a spinal ner vp \fi formpH hy ^hfiJiim-Hnn qfits roots^^jt divides, into a dorsal ramus and ^ niefitrcU ram us (Tig. 109, E). These_ r^mi,M!^_miXQ(i .Mn:^ (containing both sensory and motor fibers) an3^upply the stin and muscles of thejjack and of the lateral body wall respectively^)

(Within the cord the motor cells send out a large number of comparatively short branching processes called dendrites. By means of the dendrites the motor cell is put in communication with the collateral fibers of the sensory cells, and with fibers of commissural cells coming either from other parts of the cord or from the brain. This arrangement is shown in the diagram Fig. iii. A painful stimulus transmitted along the sensory fiber, 6, passes through the spinal ganglion into the cord. Through collateral branches it may be transmitted to the motor fiber, a, causing a muscle to contract involuntarily. This is the re f,ex path. Or the stimulus from b may be conveyed to the brain along the fiber c, and be transferred to commissural cells of which cf is a fiber extending down the cord. This also may stimulate the motor cell a, causing the muscle to contract voluntarily

Diagram of the spinal cord, showing: a motor fiber, a: a sensory fiber, b and c; and a commissural fiber, d,frum the brain ; coll., collateral fiber; sp.g., spinal ganglion.

The terms dendr^ ^^mH fj^^nraynn are of wide application. A nerve cell generally has a single process which differs from the others in being . clear, non-granular, and sh ar plv defined , often becoming very slender ' soon after leaving the cell body. It may have collateral branches, usually ■ given off at right angles, but except at its termination its branches are relatively few. It conducts impulses awa y fmm thp. rpU hQfiy. This process is the neuraxon. f xhe_d[£iidntes ^ which develop later , appear as granular, protoplasmic proces ses?^ They fork and branch freely, giving the cell a great extent of exposed surface. They may serve in obtaining nutriment, as well as in providing many opportunities for contact with the processes of other nerve cells. Dendrites conduct impu lses toward the cell body. .In the sensory cells of the dorsal ganglion the single peripheral fiber is a dendrite of unusual form, and the fiber entering the cord is the neuraxonr> ^HE Sympathetic S ystem ^ develops chiefly from the visceral o r s)rmpathetic branches of the spinal nerves. A spinal nerve typically has one such branch, extending ventrally and medially toward the^jprta, and ending in a clump of nerve cells (Fig. 109 E). QThese cells, which constitute a sympathetic ganglion , are considered to have migrated along the nerve bundles from the spmal ganglion, or possibly from the spinal corJT^ They multiply by mitosis. The successive ganglia become connected by longitudinal nerve fibers so that they form two sympathetic trunks (or cords), one on either side of the vertebral column. The ganglia of the sympathetic trunk are cervical, thoracic, lumbar and sacral. There are only three cervical ganglia , probably because some in this region have fused. <In the adult the sympathetic ganglia are each usually connected with the spinal nerves by two bundles of fibers, the white an d gr ay rami respectively. The smaller gray ramus is said to convey ^ers from the ganglion to the spinal nerve. These rami may be subdivisions of the original visceral branch?)

Besides smaller branches from the three cervical ganglia to neighboring vessels and organs, each of these ganglia sends out a large cardiac nerve, the branches of which unite to form the cardiac plexus- From this plexus and the associated cardiac ganglion the fibers continue to the heart muscle which they innervate. In the lower thoracic region the gangha of the sympathetic trunk send out nerve bundles which unite to form the s planchnic ne rves. These pass along the sides of the aorta, in front of which they form a large plexus, the coeliac [or soXdJcl^lescus, associated with which is the coeliac [or sem ilunar] ganglion (Fig. 112). (^^gjgjjjg is a net of nerves which allows a transfer of Sbers from one bundle to another; the individual nerve fibers probably do not anastomose^ QLn the sympathetic plexuses there are usually nerve cells, called gangUon cells, often found at the angles of the network. In contact with them the nerve fibers may terminate. When these cells are very abundant the plexus becomes a ganglion!) From the coeliac ganglion, fibers pass into the intestine and form a ganglionated plexus between the muscle layers, called the myenteric plexus. Branches from it innervate the muscles and pass on to make another plexus under the intestinal epithelium, the submucous plexus. Finally they come very close to the epithelium itself.

All of the nerve cells of the sympathetic system are believed to be ectodermal, and descendants of those which migrated from the spinal ganglia or central nervous system. All the sympathetic nerve fibers are processes of such cells, and they are found forming plexuses around the blood vessels and organs, including those of the intestinal tract, the bladder,. kidney, suprarenal gland and spleen. (^Two features of the sympathetic system seem fundamental; their fibers supply the viscera^ and they are so connected with peripheral ganglion cellsthat they act more or kss independently of the central nervous system.

The Cerebral Nerves

The nerves connected with the brain are not a series of similar structures like the spinal nerves. Four of them possess only ventral motor roots. Four others have dorsal sensory roots provided with ganglia, and Iateral motor roots. Lateral roots emerge just ventral to, or beneath the dorsal roots. Their fibers are the neuraxons of cells, the bodies of which remain within the central nervous system. Lateral root fibers occur as far down the cord as the sixth cervical ganglion. Instead of entering the corresponding cervical nerves, however, these fibers unite to form a bundle which passes along just outside of the spinal cord, through the foramen magnum into the skull where it becomes the accessory portion of the vagus nerve. Below the sixth cervical ganglion the lateral root elements have not been demonstrated. (It has been suggested that they pass out in the dorsal roots, and that they form parts of the ventral roots.)

Fig. 112. Diagram of the sympathetic system in its relation to the intestine. int.; A., aorta; tp. g.. spinal ganglion ; w. r., white ramus ; g. t., ganglion of the sympathetic trunk; tpl., splanchnic nerve; coe.g., coeliac ganglion ; my. pi., myenteric plexus; sbm. pi., submucous plexus.

In the diagram Fig. 113, based upon the nerves in a 1 2 mm. pig embryo, the roots, ganglia, and fundamental branches of the cerebral nerves are indicated. The ventral roots have been shaded by lines. The hypoglossal, abducens, trochlear and oculomotor nerves are ventral roots only, the first going to muscles of the tongue and throat, the other three supplying muscles of the eye. The trochlear nerve is unique in having its neuraxons pass to the upper side of the brain and cross to the opposite side before emerging. Four cerebral nerves are mixed, consisting of dorsal and lateral roots. Beginning posteriorly these are the vagus (its motor part being

Fig. 113. The Cerebral Nkrves of a 12 mm. Pir.. Xamkd in thh Ordfr of thfir Occurrkncf

Bkginning Antkriorly, with their Ganglia and Chief Branches "f (fib^'-s in the stalk of the eye. the lens of which is marked L). Ocuhmotor { Oc.) rrot/jrar (tr.) rr/j(r^w/«<z/.-serni lunar KanRlion (f.-l.); ophthalmic (oDh) maxit[.) and mandibular md. branches. AAifurrnx (Ah

and Iar>n|feal branches, rec. heinjr the recurrent nerve; the main stem proceeds to the stomach us accessory portion has an external ramus (ex.). Hypoglossal (Hy.). Frorien\ rudrmenS?^- hvii^ glossal ganRl.on (F.) sometimes sends fibers to the hypoglossal nei^'e. cJ.TS/c.?, epical nerve; called the accessory nerve), the glossopharyngeal, the inlermedius (its motor part and its largest branch forming the facial nerve), and the trigeminus. In the diagram the lateral roots are in solid black and the dorsal roots are not shaded. The accessory nerve is seen passing up the spinal cord to join the vagus. A part of its fibers turn aside in the external ramus, ex, to supply the trapezius and stemo-cleido-mastoid muscles; others remain with the vagus to supply pharyngeal muscles, and to pass down the body to the stomach. The vagus and thegIossophar>Tigeus each have two ganglia, one above the other. The lower ganglia occur near the epidermis of the embryo in positions said to correspond with the epibranchial sense organs of fishes. These organs do not develop in man, but the ganglia are permanent -structures. Closely united with the geniculate ganglion of the intermedius is the ganglion of the acoustic nerve. The latter is a purely sensory nerve to the ear. By some comparative anatomists it is considered a part of the intermedius. In the trigeminus it is to be noted that the lateral root joins the mandibular division only. The peculiar optic and olfactory nerves will be considered with the sense organs.

The sympathetic system in the head supplies the smooth muscles of the blood vessels and iris, together with parts of the pharyngeal mucous membranes and the salivary glands; it sends fibers into the periosteum. The plexuses around the large blood vessels are continuous with the sympathetic plexuses of the neck. Although the cerebral nerves do not have any regularly arranged sympathetic or visceral rami, all of them, except the olfactory, optic, and acoustic, are said to communicate with the sympathetic system. In the head there are four sympathetic ganglia, the ciliary, sphenopalaiiney otic and submaxillary , all of which are connected with the trigeminal nerve. They develop later than the semilunar ganglion from which their cells may migrate. The sphenopalatine, otic, and submaxillary ganglia are also connected with the intermedius and may receive cells from the geniculate ganglion. The otic further receives the continuation of the tympanic branch of the glossopharyngeus.

Structure of Nerve Tissue

In the following sections the HVture of nerve fibers and of nerves will be considered fiirst; then the sensory and the motor endings; next the ganglia, spinal and sympathetic; and finally the spinal cord as illustrating the tissue of the central nervous system.

Nerve Fibers. The peripheral processes of nerve cells generally appear as slender homogeneous strands varying in diameter. The smallest are found in connection with the sympathetic system and near the terminations of the spinal nerves; the largest fibers are the portions near the cord of those which have the longest course. There is no characteristic diflFerence in diameter between sensory and motor fibers.

With special methods it has been clearly shown that the nerve fiber consists of longitudinal ils imbedded in a protoplasmic neurMplasnu The fibrils begin in the cell body. At the origin of the neuraxon they may appear as if gathered into one coarse stiff fibril which distally is resolved into a bundle. The fibrils are supposed to divide but presumably they do not form networks. When the fiber branches the fibrils separate into corresponding groups. They are considered to be the essential conducting element of nerves, but it is known that conduction occurs in protoplasm in which fibrils cannot be demonstrated.

As the fibers in the embryo grow out from the central nervous system they form bundles, in and around which there are numerous nuclei.

Opinions differ as to whether these nuclei belong with the mesenchymal cells through the meshes of which the nerve is growing, or with ectodermal cells carried along from the spinal ganglia or cord. In either case they are called shealh cells, and are "so closely applied to the fibers that it becomes a matter of judgment to decide whether the fibrils are surrounded by or imbedded in the sheath celjs." Therefore some writers have thought that the nerve fiber was not the outgrowth of a single cell, but was produced by the end to end anastomosis of many sheath cells, each of which formed that portion of the nerve fiber which it enclosed. Since the fiber may be a meter long and perhaps ten thousand times the diameter of the cell body from which it comes, such an assumption seems plausible; neyertheleis it is not sustained by recent embryological investigation

Fig. 114. Non-medullatko Nkrve Fibhrs. ( (After Schiifcr.) X 400.

The cells applied to the nerve fiber may unite and thus surround ii with a delicate homogeneous sheath called the neurolemma [sheath of Schwann]. Some fibers in the adult, especially in the sympathetic system, possess only a sheath of this sort, and they are called non- medul laled ^kers (Fig. 114). Other fibers in the sympathetic system and near the nerve terminations may be surrounded only by ordinary connective tissue; these axe ncm-medullatedJijstL without a neurolemma [ naked axis cylinders]. (Non-medullated fibers of the sympathetic system are often called Remakes fibers.) The fibers of the spinal nerves are generally characterized by a deposit of myelin, found between them and the neurolemma. The fibers with a myelin sheath are called meduUated, and the fibers themselves within the myelin sheath, whether they are dendrites or neuraxons, are called axis cylinders.

Fig. X15. Mkdullated Nkrve Fibers. A-D, Longitudinal sections ; E-l, cross .sections. (A. B, after (;edoelsl; C, E, F, after Hardesty; D and I, osmic acid prepRrations. after Pre'nant and Scymonowice ; G, alcoholic presen-ation, after Koelliker; H, picric acid preservation, after Schafer.) t. C, Axis cylinder; In., incisure ; my., myelin ; nu., nucleus of the neurolemma.


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. It exists as an emulsion, and appears very white macroscopically. Between the myelin globu les there is a net woxk of neurokeratin, a substance unstained Jby Xismic Acid and not dissolved by ether. FigN^s, A and B, show the neurokeratin network after treatment with ether, sqrrounding the axis cyhnder^^.c. The meshes vary greatly in diameter, Dteqoming coarse with the rapid, post mortem coalescence of myelin droplets.^^ig. 115, C, shows a heavier framework which toward the right of the figure tends to form conical layers, the axis cylinder penetrating their apices; in E a cross^^ection of C is drawn showing a myelin vacuole, my, encircling the fiber. In specimens stained with osmic acid (D), the myelin is very dark and the framework hght. The latter is prominent only in obhque lines called incisures [or Lantermann's segments]. The lines seen on the opposite sides of the fiber are interpreted as optical sections of a cone of neurokeratin. A cross section of D through an incisure would appear as in I. Successive incisures may point in opposite directions. X^^Y do ^o^ sill represent perfect cones, buf ^in that form they are characteristic post m6|-tem figures. Fig. 115, F, G, and H, show other cross sections of medullated fibers in which the neurokeratin is arranged radially or in concentric layers.

At regular intervals the myeUn sheath is more or less interrupted by nodes [of Ranvier]. , The intervals vary from 80 /i to a milUmeter, being shorter in growing fibers and in the distal portions of adult fibers. The branching of medullated fibers occurs at these nodes. Fig. 116, A, an osmic acid preparation, illustrates one interpretation of the myelin and nodes, according to which the sheath cells are thought to be wrapped around the axis cyUnders, and to contain within them the myeUn which develops like fat in the mesenchymal cells. The nodes (A, no) are at the junction of two sheath cells; and there the outer cell membrane or neurolemma is continuous with the axolemma or inner cell membrane, the latter being in contact with the axis cylinder. It accords with this view that the neurolemma usually has but a single nucleus, found midway between two nodes. Surrounded by very little protoplasm it occupies a depression in the outer surface of the myelin.

Fig. 116. Nodes. A, Diagrram of the intracellular explanation of myelin; B, the cross obtained with silver nitrate : C, the biconical enlargement (after Gedoclst); D, intercellular myelin (after Hardesty); a. c, axis cylhicler ; ax., axolemma : my., myelin ; ne., neurolemma ; no., node.

When nerve fibers are treated with a solution of silver nitrate a precipitate occurs at the nodes and spreads along the axis cylinder forming a cross (Fig. ii6, B). This has been interpreted as indicating a penetrable intercellular substance at the nodes through which nutriment has access to the fiber Silver nitrate sometimes causes a transverse banding of the axis cylmder, which is considered artificial and without significance. In crossing the node the fibrils may spread apart forming a "biconical enlargement." As shown in C, the fibrils in the midst of the enlargement have been said to be thickened. The same figure suggests that the neurolemma is not continuous with an axolemma but passes the node without interruption. Q^his is clearly shown in D, where the myelin layer also, though constricted, is unbroken. The myelin has therefore been regard^ EiMflli[i-M ^^ thp^a^ ^Y^inder. The inter-fibrillar subst^ce

Fig. 117. Mbdillated Nerve. Partook a Cross Sectio.n ok the Human Median Nbrve. x 20.

the nerve fib er has been said to present ma ny c har acterist ics of myelin. The clo se relation of myelin to the_ cylinder is shown in " peripheritl jdcgeneration. When a nerve is severed, that portion of the axis cyUnder which is cut off from the cell body from which it grew, degenerates by fragmentation. The myelin at the same time breaks up into drops of a different chemical nature which later disappear. The sheath cells multiply. Recently it has been stated that the myeUn should be considered ail intercellular substance* (Tuc to a' transformation of tissue fluid by the joint activity of the axis cylinder and sheath cells. It first appears in the embryo as vesicles attached to the nerve fiber. These unite to form a nodular or beaded layer which later becomes smooth. The axolemma is considered a condensation of the myelin framework such as occurs also just beneath_ the neurolemma. The myelin itself is said to be derived from the blood,

Nerves are bundles of nerve fibers enveloped in connective tissue sheaths. According to the nature of their constitutents they are classed as meduUaled and non-medullated, a distinction which the student should remember to record.

The spinal and cerebral nerves consist mostly of medullated fibers of varying diameter (2-20 /i), scattered among which are a few that are non-medullated. Medullated nerves are white in reflected light. They are surrounded by loose connective tissue [the epineurium] which contains lymphatic and blood vessels, and small nerves, and has many elastic fibers. It extends around the entire nerve and between the several well defined bundles of which a large nerve consists (Fig. 117). Each of these bundles is covered by a dense lamellar layer of flattened connective tissue, called the perineurium (Fig. ii8). The cells in the perineural layers are in contact with one another along their borders so that on surface view they resemble a mesothelium. The perineurium sends septa into the nerve bundle and becomes continuous with the connective tissue which, outside of the neurolemma, surrounds each individual nerve fiber [Henle's sheath]. The inner extensions of the perineurium may be called internal perineurium (or endoneurium). The perineurium contains capillarie*s, generally parallel with the ner\'e fibers, and tissue spaces, but no lymphatic vessels. The outer sheaths of the nerves arc continuous with the dura mater of the cord and brain.

Fig. 118. Medullated Nerve. Part ok a Cross Section of the Human Median Nerve. X 220.

The large sympathetic nerves vary in color. The splanchnic nerves contain many medullated fibers and are whiter than the nerves of the plexuses. Medullated fibers in the latter are few and very slender. Xon medullated nervous ti ssue is gra^. A part of the medullated fibers of the sympathetic nerves come directly from the spinal nerves, and a part arc medullated processes of the sympathetic ganglion cells. Small nonmedullated nerves are shown in Fig. 119; A represents a nerve which is easily recognized by the two large nerve cells which it contains; B is a bundle of fine fibers containing a few nuclei, probably of connective tissue.

Fig. 119. NoN-MKUi'LLATRD Nervks, FROM A Cat's Intkstink.

A, From the submucous and B, from the myenteric plexus, c. t.. Connective tissue; n.. sympathetic, non-medullated nerve fibers; n. C, nerve cell ; s. m., smooth muscle.

/"TVip rprnprn^|inn nf <tTnfl11 nprvp<; inj)rdinary sections niay be f acilitated, by re membering that they are fibrous bundles extending through connective tissue and found in the same situations as the vesselsT The latter are tubes hned with endothelium. Sometimes they are filled with corpuscles (Fig. 118) but the corpuscles never appear fibrous and usually stain unhke anything else in the specimen. Ner\'^es differ in texture from the white fiber of connective tissue, which forms a diffuse network or layer instead of occasional distinct circumscribed bundles!)

Sensory Endings. The way has already been described, in which ectodermal cells become detached from the medullary tube to form spinal and cerebral ganglia, afterwards becoming bipolar and then T-shaped, sending a long dendrite through the nerve bundle to the periphery. Soon after it leaves the cell body, this process becomes surrounded by the neurolemma and myelin sheath. Its branches are very few until it nears its distal end when it forks repeatedly at the nodes. Finally it loses its sheaths and is resolved into many small fibers which terminate in contact with epitheUal, connective tissue or muscle cells. These terminal branches of the dorsal root fibers are the sensory nerve endings. Apart from those of the special sense organs, to be described with the eye, ear, etc., they are as follows.

Free nerve endings. Sensory nerves to the epithelia, such as the epidermis, or that which forms part of the mucous membrane of the mouth, or the corneal epithehum, lose their myelin sheaths and divide repeatedly in the connective tissue just beneath. The unsheathed slender fibers thus formed pass between the epitheUal cells where they ramify further, and terminate with pointed or club-shaped ends (Fig. 120). Such free endings are too dehcate to be seen in ordinary preparations. Sometimes the terminal fibers in the lower layers of the epidermis expand into crescentic structures called tactile menisci (Fig. 121). An epidermal cell, the base of which rests upon a meniscus, may modified so that it is larger and clearer, having a more vesicular nucleus, than those around it. Cells thus differentiated are called tactile cells.

Fig. 120. FrkkNervk Ending, in EpiTHELIl'M. GOLGI Preparation. (After Retzius.)

(The sensory nerves to muscles similarly may end freely, or may be in special relation with modified muscle fibers^ In the former case (Fig. i3i> sensory fibers) the nerves become non-medullated and their fibers y arborize extensively, terminating in long slender filamenjts._between the muscle cells. . The specially modified muscle fibers in contact with which sensory nerves end, constitute the muscle spindle s (Fig. 105, p. 88). ^ These are bundles of from 3 to 20 muscle fibers, i to 4 mm. long, varying in width from 80 to 200//. They are surrounded by a thick connective tissue sheath or capsule, continuous with the perimysium and described as divided into an inner and an outer portion by a considerable tissue space filled with fluid. (Jhe muscle fibers of the spindle are distinctly striated toward their tapering and very slender ends In their middle

Fig. 121. From a Vertical Section of thk Skin of the Great Toe of a Man Twenty-five Years Old. X 240.

The outlines of the cells and the nuclei of the epidermis can only be indistinctly seen, x, Tactile cells

in the corium, resting upon the ramifications of a delicate nerve fiber.

portions the striations are obscure; there the sarcoplasm is abundant and the muscle nuclei are numerous. Three or four nerves terminate in each muscle spindle. Their connective tissue sheaths blend with the perimysial capsule, and they branch and lose their myelin as they pass through this capsule to the muscle cells. v^They may encircle the muscle fibers of the spindle, forming spirals or rings (as in the upper part of Fig. 122) or they may form a panicle of branches with enlarged club-shaped endSP Muscle spindles are not found in the muscles of the eye, pharynx, larynx, and oesophagus, the muscles of expression, the diaphragm and the ischio- and bulbo-cavemosus muscles. They are especially numerous in the muscles of the hand and foot. (jThe nerves of the spindles are stimulated by pres- ' sure caused by the contraction of adjoining muscle fibers

In tendon s there are said to be free nerve endings, but the sensory fibers which terminate in tendon spindles are better known. These are small portions of the tendon, from i to 3 mm. long, 170 to 250 /^ wide.

containing many nuclei and staining more deeply than the surrounding tendon. They are enclosed in sheaths of ordinary connective tissue.

Fig. 123. Tendon Spindle of an Adult Cat. Sd.

Fig. 124. Thk Lkit Portion of Fig. 123. X 345

The few nerve fibers which terminate in a tendon spindle lose their sheaths and branch freely, ending in clubshaped enlargements (Figs. 123 and 124). They are found in all tendons and serve to transmit the sensation of tension, being active in connection with coordinated movements.

In connective tissue, sensory nerves may either end free or surrounded with a connective tissue capsule. In the subcutaneous tissue near the coils of the sweat glands, and in the corium of the fingers and toes, there are terminal cylinders [of Ruflmi] which resemble tendon spindles in the

Fig. 122. Muscle spindle of an adult cat.

way that the nerves ramify (Fig. 125). 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 such as are found along terminal nerve fibers generally and which are not considered artificial. Some authorities describe the interlacing terminal branches as ending blindly, but others believe that 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 of the corpuscle, and the myelin sheaths are lost just inside the capsule. Terminal corpuscles have been grouped as iactUcy genital , bulbo us^ articular^ {cylindrical), and lamellar.

Fig. 125. Terminai. Cylinder. (After Ruflliiii, from Ferguson's Histology.

Fig. 126.--TACTI1.F. CoRPi'scLE from a Pkri-knoicular Section ok the Great Toe of a Man Twentyfive Years Old. y 560. n, Medullated nerve fibers; e, varicosities; h, connective tissue sheath. The nuclei are invisible.

Tactile corpuscles [of Meissner] are elliptical structures, 40-100 /i long and 30-60 n broad (Fig. 126). They are characterized by transverse markings due to the corresponding elongation of their capsule cells and nuclei. From one to five medullated fibers enter the lower end of a tactile corpuscle, losing their sheaths on entering. Some fibers may pass straight through the axis of the corpuscle, the^others making spiral turns about them before breaking up into numerous varicose branches. Tactile corpuscles are found in certain of the connective tissue elevations (papillae) just beneath the epidermis, being 'especially numerous in the soles and palms (23 in i sq. mm.) and at the finger tips; also "in the nipple, border of the eyelids, lips, glans penis and clitoris.

Fig. 127. Genital Corpuscle from the Glans Pknis of Man. Mkihylhne Blue Stain. (After Dogiel, from Bohm and von Davidoff.)

Fig. 128. Bulbous Corpuscle from the Conjunctiva OF Man. Mf-THVi.kne Blue Stain. (After Dogiel, from Bc>hm and von Davidoff.)

(Fig. 127) 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 beneath the epithelium of the glans penis and clitoris and the adjoining structures.

Bulbous corpuscles [of Krause] are smaller than the genital corpuscles and 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 vary in length from 20 to 100 /i; they have thiimer capsules and receive fewer nerves than the genital corpuscles which they resemble (Fig. 128). 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. 129). The fiber is surrounded by a semifluid

Fig. 129. Cylindrical Corpuscles, from InTKK.Mt SCULAR SkPTUM OF CaT. METHYLENE Blue Stain. (Huber.)

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 [Pacinian corpuscles] are macroscopic eUiptical structures, 2-4.5 ^nni. long and 1-2 mm. wide (Fig. 130). They may have as many as fifty concentric layers of flattened capsule cells between which there are spaces containing 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 inner bulb without obvious branches, sometimes being flattened and band-like; it may fork at its further end or form a coil of branches. 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, the connective tissue around large blood vessels and nerves, and in the tendon sheaths ; also in the serous membranes, particularly in the mesenteries. As they are usually cut obliquely or transversely the student should expect to find the lamellae completely encircling the inner bulb.

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 s mooth muscles are a part of the sympathetic system. They ar e non-meduIlatecT fibers which branch repeatedly^ forining plexuses. From th e 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 t hicken i ng s. Probably each muscle cell receives a nerve termination. Except that the nerve endings in heart" muscle are a little

Fig. 13c. Small Lamellar Corpusclk from the Mesentery of a Cat. X 50.

The cells lining the capsules can be recognized by their shaded nuclei. The myelin of the nerve fiber may be traced to the inner bulb.

larger, often provided with a small cluster of terminal nodules, they are like those of smooth muscle. They belong with the sympathetic system. .Th^accessory_fibers of the xagua which enter the cardiac plexuses, are not known to terminate upon the muscle fibers)

Fig. 131. Motor Nerve Endings of Intkrcostai. Misclk Firkks of a Rabbit. X 150 S^^gjed musrl^j > are innervated by the neuraxons of the ventral roots, which grow out from cell bodies remaining within the central system. These neuraxons, as medullated -fibers, extend through the spinal and certain cerebral ner\Ts to the muscles. They form plexuses of medullated fibers in the perimysiuni^from which branching medullated fibers pass on to the muscle (Fig. 131). E ach m uscle fiber receives one of these branches, or

sometimes two placed near together. They are usually implanted nearjhe middle of the muscle fiber. CThe

Fu;. 132 Motor Pi.atks. , Surtruf view, tiom a j^uiiiea pi;;; B, vertical section, trt)m a he<lKebo«:. (Atler Hohm and von I)a\i<lof!.) g., dranular substance of tbe niotf>r plate; m., striate<l muscle; n., iierAe fiber ; t. r., terminal ramifications of the neiA e fiber.

connectrve tissue shcatlTof the nerve blends with the perimysium; the neurolemma is said to be continuous^^itlT the sarcojemma, the nerve having become a ttached to jhc embryonic muscle fiber before_the sarcoIcmrnaThad developcdA Under this membrane the myelin sheath ends abruptly, and the fiber ramifies in a granular mass considered to be modified sarcoplasm. It _may contain muscle nuclei. This granular mass with the nerve ending appears as a distinct elevated area, estimated to average from 40 to 60 // in diameter, and has been named the motor plate. A surface view and a section of a motor plate are sho\\Ti in Fig. 132.

Ganglia. The ganglia are enlargements, usually macroscopic, occurring in the course of the peripheral or sympathetic nerves. They always consist of nerve fibers between which there are rows or rounded groups of the bodies of nerve cells. Nerve cell bodies vary in diameter from 4 to 150 /i. Thus they include some of the largest cells in the body. Each has a single round or oval nucleus which appears vesicular because of its small amount of chromatin. It contains usually one large round nucleolus. These nuclei are so characteristic that the student should soon learn to recognize them. Near the nucleus the centrosome has been detected, sometimes represented by a number of granules; but mature nerve cells never divide and if destroyed they cannot be replaced. In ordinary

Fig. 133. Longitudinal Section through a Spinal Ganglion of a Cat. X 18.

specimens the protoplasm is densely granular. There is no cell membrane. Except in the embryo, nerve cells all have one or more processes; and according to the number of these, one, two, or several, they are designated unipolar, bipolar, and multipolar respectively. The processes cannot be traced in ordinary specimens because of their thick entanglement with those of other cells. In studying them the special methylene blue and silver (Golgi) methods are employed. If pieces of very fresh nerve tissue are placed in a dilute solution of methylene blue, after an hour or more the processes of certain cells are stained so that they can be followed satisfactorily. By Golgi's silver method a black precipitate occurs in and on individual nerve cells, following their branches to their smallest subdivisions, whereas similar adjoining cells are entirely unaffected. This extraordinary method is of the greatest value, but it is capricious and the silhouettes produced are in part coarse and artificial appearances.

The ganglia are surrounded by connective tissue sheaths, continuous with the perineurium, which send prolongations into their interior to invest the cell bodies and fibers. They contain an abundance of blood vessels so that a cell body may be surrounded with capillaries. The spinal and sympathetic gangUa will be described in turn.

Spinal ganglia are found on the dorsal roots of spinal nerves; similar

LoTi^f^ituflina] view of medullated nerve fibers. Surface view of

nucleated shealh

Fig. 134. From a Cross Sbction of the Skmilunar Ganglion of Man. X 240,

The cell processes cannot be seen. At X the protoplasm of the jran>flir>n cell has retracted and simulates a process, in the axis of the transversely cut nerve fibers the axis cylinders are seen in section.

Structures occur on the dorsal roots of the cerebral nerves. The general relations of the cell bodies and fibers are shown in Fig. 133, a longitudinal section through the dorsal and ventral roots. Fig. 134, from the semilunar [Gasserian] gangUon of the trigeminus, shows the component structures on a large scale. In the upper part of the figure there are characteristic nerve cells such as have the T-shaped process, the development of which from bipolar cells has already been described. The processes are not seen in the section. Each of these cell bodies is surrounded by a nucleated capsule said to be continuous with the neurolemma of its fiber. Fig. 135 shows one of these cell bodies containing canaliculi which have been regarded as nutritive passages from the exterior, and as secretory or excretory vacuoles. Fig. 136 is a similar cell containing a reticular network within its protoplasm. Nerve fibers branch over the outer surface of ganglion cells, forming pericapsular and pericellular nets or baskets, and have been said to penetrate the protoplasm. This, however, is denied, and such formations as are represented by Fig. 136 are thought not to pass outside of the cell. Ganglion cells often contain areas of yellow or brown fatty pigment granules which increase with age.

The results of special investigations of the course of the dorsal gangHon fibers, made by the methylene blue method, are shown in the diagram, F^g- ^37- The large round cells (i) give rise to a single spirally twisted process which begins at the apex of a conical elevation on the cell body. The spiral fiber has a neurolemma and acquires a myelin sheath. It may give off collateral branches (2). At the first or second node, sometimes further on, it divides into a cdlulipekU or afferent branch, which is an axis cylinder with a peripheral sensory ending, and a cellulifugal or efferent branch which enters the spinal cord (Fig. III). The cellulipetal fiber may have a branch in the dorsal ramus and another in the ventral ramus (2); and the cellulifugal fiber may fork near the cell body (3) or at some distance from it (2). Besides the large cells there are similar smaller ones, the fibers from ^ which have little or no medullary sheaths (4). It is to be noted that in all these forms the cell bodies become virtually appended to single fibers, which in relation to the central nervous system are afferent.

A second type of cell, which occurs less frequently, is the round unipolar form (6) the process of which divides into many medullated branches. After losing their myelin these form pericapsular and pericellular ramifications around the cell bodies of the first type. Each of the latter is in relation with branches from several cells of the second type. A third form is a multipolar cell with two medullated fibers which are thought not to pass beyond the Umits of the ganglion (7).

Fibers from sympathetic cells enter the ganglion from the periphery and branch about the blood vessels and cells of the second type. Through the cells of the second type a few sympathetic fibers are put in communication with a large number of T-cells. Apparently in mammals there are no fibers which traverse the spinal ganglion without entering into relation with its cell bodies. The observation that there are types of spinal ganglion

Fig. 135. Spinal Ganglion Cell of an Adult Cat. X 430.

Fig. 136. Spinal Ganglion Cell of a Newborn KitTBN.1 (Copied after Golgi.)

Fig. 137. Diagram ok vhk Nkrvois Elements of a Spinal Gan(;lio.n, Based upon Methylene Blue Preparations. The sensory fibers are represented by continuous lines, the sympathetic fibers bv dotted lines, the motor fibers by linear series of dashes. The medullary sheaths of the motor fibers of the ventral root have not been drawn.

cells with processes confined within the ganglion, and that some of the cells have non-medullated fibers, accords with the fact ascertained by counting, that the ganglion may contain about six times as many cells as there are meduUated fibers in the dorsal root.

Sympathetic ganglia consist of smaller cell bodies, often pigmented, and sometimes having two nuclei, and of fibers some of which merely traverse the ganglia. The cells are enveloped in nucleated sheaths. They include three types of multipolar cells shown in Fig. 138. Most of the cells are of rounded oval form, often flattened, having stellate spiny dendrites and a non-meduUated neuraxon with very slender collateral

Motor, Sensory spinal V , ^ nerve fiber.

Fig. 13S. Diagram of the Elements of Two Sympathetic Ganglia, Based upon Bli'E Preparations.

branches (i). These are motor cells, and their neuraxons terminate in contact with smooth muscle cells. The second type (2), possibly sensory, includes rounded polygonal cells with slender dendrites which extend in the sympathetic nerves even to the neighboring gangUa. Their neuraxons may acquire myelin sheaths at some distance from the cell body or may remain non-meduUated. They pass to other ganglia but their termination is unknown. Cells of the third typQ (3) are few in the large ganglia and are not found in small ones. They have long dendrites which form a * * general peripheral plexus " but do not extend beyond the limits of the ganglion. Their neuraxons enter the sympathetic nerves as non-medu Hated fibers, the destination of which is unknown. Sympathetic gangUa contain also stellate connective tissue cells, and chromaffine cells to be considered presently. The ganglia may be traversed by sensory medullated fibers to lamellar corpuscles, and by medullated motor fibers which lose their myelin sheaths and have non-meduUated collateral branches. The motor fibers and their collaterals terminate in rather coarse pericellular ramifications about the sympathetic cells of the motor type. There are other nerve fibers, non-medullated and varicose, which form pericapsular plexuses, and these are considered to be branches of sympathetic cells.

Paraganglia are masses or cords of cells which originate in the embryonic sympathetic gangUa, and are characterized by being colored yellowish brown by preserving fluids containing chromic acid or chromium salts. The cells are therefore called chromaffine (meaning that they have an affinity for chromium, and not, hke ^chromatic material,' for coloring matters generally). The paragangUa are either closely or shghtly connected with the sympathetic nerves. In the latter case they are applied to large vessels, and in the fetus, between the branches of the spermatic vessels, to the paroophoron and paradidymis. The glomus caroticum at the bifurcation of the carotid artery, and the glomus coccygeum associated with the median sacral arter>% are knots of vessels both of which contain clumps of chromaffine cells. The organs discovered by Zuckerkandl at the origin of the inferior mesenteric arterj' may be classed with them. Single chromaffine cells, or small groups of them, occur diffusely in the sympathetic ganglia and nerves. The entire medulla of the suprarenal gland in the higher vertebrates is composed of them. Since the extract of such cells, on intravenous injection, causes a marked increase in the blood pressure, the chromaffine cells are considered to secrete into the blood a specific substance which maintains the normal tonus of the vessel walls.

Spinal Cord (Medulla spinalis), Development. The early development of the medullary tube has been shown in Fig. 109, p. 92. The tube at first consists of separate cells but these soon unite to form a syncytium. Those nuclei of the syncytium which border upon the central canal divide repeatedly by mitosis and many of them are forced outward radially. The protoplasm of the syncytium increases more rapidly than the nuclei, and forms a non-nucleated network at the peripher>' of the tube; this is the white layer [sometimes called mantle layer]. The fibers from the spinal ganglia enter its dorsal portion and grow up and down the medullary tube through its meshes, thus forming the oval bundles. Meanwhile the nucleated layer becomes divisible into two portions, a thick ependymal layer composed of undiflferentiated cells around the central canal; and a gray layer [mantle layer] composed of cells which have moved outward and become partly differentiated. The gray layer is at first triangular, being thick ventrally and narrow dorsally. It consists of two sorts of cells, the neuroglia cells (glia cells), which are the cells of the protoplasmic syncytium; and the nerve cells (in their young stage, called neuroblasts), which are imbedded in the neuroglia network and send out processes to ramify among its meshes. The neuraxons of the motor cells grow out from neuroblasts in the ventrolateral part of the gray layer; after crossing the white layer, they pass out of the medullary tube as fibers of the ventral roots. This stage of development is shown in Fig. 109, E. Blood vessels are seen growing into the tube under the dorsal roots and near the ventromedian line. They carry some connective tissue cells with them, to mingle with the neuroblasts and neuroglia, both of which are ectodermal.

Fig. 139 represents a later stage in which the form of the adult cord is clearly suggested. The walls of the dorsal portion of the central canal have fused and disappeared so that the canal is reduced in size.

It is surrounded by an ependymal layer which is becoming thinner, since its cells are being added to the gray layer faster than they are replaced by mitosis of the inner cells. The gray layer in the preceding stage showed two ventral protuberances, one on each side. These extend the length of the cord and are known as the ventral columns [horns]. In the present stage in addition to these, there are two dorsal columns [horns] which have been formed by the dorsal proliferation of the ependymal layer. As a whole the gray is shaped like an H. That portion which extends from side to side beneath the central canal is the ventral gray commissure. The white layer has become wider. Its neuroglia network has a predominant radial arrangement. Nuclei are found in its strands of neuroglia which have become fibrous, but it lodges no nerve cell bodies. It is permeated with the processes of nerve cells, the bodies of which remain within the gray layer, or the spinal ganglia. On the outer surface of the cord there are longitudinal grooves which form the boundaries of certain subdivisions of the white layer. These grooves are the dorso-median sulcus; the dorso-laieral sulcus, along which the dorsal roots enter the cord; the ventrolateral sulcus, along which the ventral roots leave the cord; and the ventromedian fissure, which unhke the others becomes a very deep narrow depression. Between these four grooves the white substance on either side of the cord forms the dorsal, the lateral, and the ventral funiculi. Each dorsal funiculus receives the entering fibers from the dorsal roots on one side of the cord; it represents the oval bundle which has enlarged and been folded in toward the median dorsal Une. Later a dorsal median septum becomes more evident separating the two dorsal funiculi. Ventrally there is a narrow layer of white substance extending from one side of the cord to the other; this is the ventral white commissure.

Fig. 139. Spinal Cord of a Rabbit Embryo of 20 Days. C. C, Central canal ; d. C* dorsal column ; d. m. 8., dorsal median sulcus; d. r., dorsal root; ep., ependymal layer; v. c, ventral column ; v. g. c. ventral j^ray commissure; v. m. !.. ventral median fissure ; v. r., ventral root ; v. w. C, ventral white commissure; w. I., white layer (lateral funiculus).

Fig. 140. Cross Section of the Lumbar Enlargement of the Human Spinal Cord. X S.

In the adult cord (Fig. 140) the central canal is usually reduced to a cavity 0.5 to i.o mm. broad; sometimes it is obliterated. The canal is surrounded by the ependyma which appears as a single layer of neuroglia cells. Around the ependyma is the central gray substance, containing special neuroglia cells to be described later. In addition to the ventral gray commissure of the younger stage, there is now a dorsal commissure, by which the vertical portions of the gray H are united dorsal to the central canal. Besides the dorsal and ventral columns, a lateral column may now be recognized as a bulging of the ventral column on a line with the central canal. Lateral colunms are most evident in the upper thoracic part of the cord. On the lateral side of the dorsal column there is a network of strands of gray substance called the reticular formation (formatio reticularis). Near the dorsal commissure in the dorsal column there is an JD^ortant g roup o f nerve cell bodies named the dorsal nucleus [column of Clark]. (* Nucleus* is a term applied to many such groups of cell bodies m thehjaixL). The dorsal nucleus extends through the _thQracic cprcL and is well defined in the anterior lumbar portion; it is not wholly absent from other parts of the cord. Toward the tip of the dorsal column there is a macroscopic, apparently gelatinous mass called the gelatinous substance (substantia gelatinosa); and dorsal to this there occur successively the spongy zone, and the terminal zone (zona spongiosa and zona terminalis). The latter consists chiefly of nerve fibers running lengthwise of the cord. The dorsal median septum, generally described as formed of compressed strands of neuroglia, is well marked; it resembles the ventral median fissure since the walls of the latter have been brought so close together.

Fig. 141. Neuroglia Cri.i.s and Fibers from the Spinal Cord of an Elephant. { //a f desfy, Iroin Ferguson's Hislology.) The letters indicate the neuroglia cells. I., a leucocyte. Benda's stain. X 940.

Structure of the cord. From the preceding account of the development and topography of the cord, it is evident that there are three layers tobeexaminedj the white layer, the gray layer, and the ependyma; these may be considered in turn.

The white substance [matter] consists of a sync>1:ial framework of neuroglia through which pass blood vessels? and nerve fibers mostly medullated. The myelin sheaths of the latter produce the very white macroscopic appearance of this layer when freshly cut. The nature of the neuroglia syncytium is seen in the longitudinal section. Fig. 141. StifiF fibrils have developed in its exoplasm, and they are continuous from one cell territory to another. As the nerve fibers which occupy the neuroglia meshes increase in number, and" m" "size by becoming mediillatQ^i, the neuroglia nuclei surrounded by protoplasm are compressed into stellate forms (Fig. 144, A). In^the GolgTpreparations they appear as in Fig. 1 42, and are described as long rayed, and short rayed or mossy cells. These forms represent clumps of neuroglia fibers, sometimes clogged with precipitate, in the center of which there may or may not be a nucleus. Fig. 143 shows the appearance of the neuroglia net in ordinary sections. Over the outer surface of the cord it makes a dense feltwork, generally free from nerv-es. It has been called the external limiting membrane. Outside of it is a very vascular connective tissue layer, the pia mater. The figure shows a prolongation of the pia mater, containing blood vessels, into the white substance. It has not been established beyond doubt that such ingrowths of connective tissue may not take part in forming supporting tissue around the nerves.

Fig. 142. Neuroglia Cells from the Brain ok an Adult Man. Golgi Method. X 280.

The nerve fibers of the white substance vary in diameter, the coarsest being found in the ventral and the lateral parts of the dorsal funiculi ; the finest are in the median parts of the dorsal and lateral funiculi. Elsewhere coarse and fine ones are intermingled. Their general direction is parallel with the long axis of the cord. Like other nen-e fibers they consist of neuroplasm and fibrillae. Most of them are meduUated and in cross section the myelin often forms concentric rings. Although a few

observers have described nodes it is generally considered that there are no nodes in the central nervous system." During the development of the myelin, fibers have been found encircled by sheath cells, Fig. 144, B. In longitudinal view, these sheath cells are seen in depressions of the myelin, where they greatly resemble the neurolemma cells of peripheral nerves. With the increase of myelin they become very slender and can seldom be detected in the adult. It is ordinarily stated that the medullated fibers of the central nervous system are without a neurolemma.

The gray substance [msLtter] is composed of a neuroglia framework containing capillary blood vessels and some larger ones, together with the cell bodies and non-medullated processes of many nerve cells. The processes run in every direction. It differs from the white substance, therefore, in the absence of myelin, the presence of nerve cell bodies and the confused courses of the nerve fibers.

Fig. 143. From a Cross Section of the Human Spinal Cord in the Rkgion of the Lateral Funiculus, x iSo.

Fig. 144. A, Neuroglia cells and nerve fibers from a cross st^nion of the spinal cord of an elephant. B, Neuroglia cells, nerve fibers and sheath cells, from the spinal cord of a pig, 2 weeks after birth. C, Isolale<l fiber from the cord of 21 cm. i>ig enjbryo, stained with osmic acid. (After Hardesty.) t. C, Axis cylinder; my., myelin ; n.. neuroglia nuclei; n. !., neuroglia fibrils; S. c.« sheath cell.

The cell bodies belong with three types of cells. The largest are the tnotor cells, 67 to 135 /^ in diameter, which form a group in the ventral column. (In thecervical and lumbar enlargements of the cor d (F ig. 140) the group is divided into dorso-laterai and ventro-mcdial portions.) Cell bodies like those of the motor cells are represented in Figs. 145 and 146. The former shows the fibrillar structure of their protoplasm, and the latter the groups of granules, chro matic bo dies (Nis srs_ bodies) which may occur between the fibrils. These are rounded or angular masses which are not limited to motor cells. They become reduced or disappear with

Nissl's bodies.

Fig. 145. Nerve Cell of the Spinal Cord Fig. 146. Nerve Cell 6h the Spinal Cord

OF A Child, x 430. of a Dog. X 600.

fatigue, in old age, and in certain diseases and poisonings. It is supposg d t hat they are n utritive rather than nervous elenients. After preservatipn in a lcohgl they stained with jnetly^lene blue. In the motor cells the Jatty pigment may be abundant, but often in ordinary specimens these special features are invisible and the protoplasm seems densely granular. The processes of the motor cells are dendrites, which may extend into the ventral and lateral funiculi, and even into the dorsal funiculi, and neuraxons which leave the cord in the ventral roots and proceed to the striated muscles. The neuraxon begins as a slender nonmeduUated fiber at the tip of a clear * implantation cone' and acquires its myelin sheath as it crosses the white layer. Ordinarily it has no collaterals; when present they are very small.

Cell bodies of the second tj'pe are more numerous and smaller than the motor cells. They occur singly and in groups throughout the gray substance. Their dendrites are long but with comparatively few branches. Their neuraxons give ofT many collaterals in the gray substance and enter

the lateral and ventral funiculi, rarely the dorsal. Sometimes they cross to the opposite side of the cord through the gray commissure before entering the white substance (Fig. 147). In the white they fork, sending processes up and down the cord. These give oflF collaterals which re-enter the cord and branch about the motor cells, the main fiber terminating like its collaterals. These cells put the different levels of the cord in communication. The neuraxons from the dorsal nucleus (Fig. 147) differ from these in that

Fig. 147. Diagram of the Spinal Cord. The principal fiber bundles are outlined on the left : the predominant courses of the nerves within them

are indicated on the right.

Dorsal funiculus :

f. g.y lascicul us gracilis [column of Goll] .

f. c.wL _ " ciiTieaTtrrtc'dTnimT of Burdach].

lateral funiculus :

f.C. I., fasciculus cerebrospinal is lateralis [crossed pyramidal tract].

f. c, '* cerebellospinalis.

f. V. g., ventrolateralis superficialis [Gowers' tract].

f. I. p., '* lateralis proprius [ground bundle] . Ventral funiculus :

I. ¥. p., fasciculus ventralis proprius.

f. c. v., " cerebrospmalis ventralis [direct pyramidal tract].

Columns, d. c, dorsal ; I. c, lateral ; v. C, ventral.

d. n., dorsal nucleus. Sulci, d. m. 8., dorsomedian ; d. I. 8., dorsolateral ; v. I. 8., ventrolateral ; v. m f., ventromedian fissure.

their neuraxons go to the cerebellum in a bundle called the fasciculus cerebellospinalis. The spindle shaped cells of the zona spongiosa are also of the second type.

The third type is characterized by having all of its processes, the dendrites and neuraxon, remain within the gray substance. The neuraxons are muc h branched, and may cross to the opposite side of the cord.

Qrhere are therefore three t)^es of nerve cells in the gray substance, namely, (i) the cells with processes which enter the peripheral nerves; (2) cells with processes limited to the central nervous system and extending through its white substance from one part to another; and (3) cells with processes limited to the gray substance.

The fibers of the central nervous system are the processes of these three t}pes of cells together with those which enter from the peripheral ganglia. These fibers are arranged in bundles or fasciculi as they traverse the white substance. The boundaries of the bundles are not indicated in ordinary sections and are never sharply outUned. They have been determined in various ways, such as cutting certain parts of the cord and observing in sections the path of the fibers which degenerate and lose their myelin in consequence. These results are confirmed by the examination of embryos in which certain fiber tracts develop their myelin sheaths earlier than others. It has been found that each dorsal funiculus includes two large fasciculi, th e cuneale and ^rgct/g ^ respectively. The cuneate fasciculus which is the more lateral, receives the fibers of the dorsal root. In it they divide into ascending and descending fibers and give off the reflex collaterals to the motor cells as shown in the diagram (Fig. 147). The ascending fibers in their course up the cord to the brain approach the median septum thus entering the gracile fasciculus. The manner in which they communicate with the cells of cerebral hemispheres will be considered with the brain.

The lateral funiculus of the cord consists of four fasciculi, (i) The cerebellospinal fasciculus consists largely of fibers from the dorsal nucleus ascending to the cerebellum. (2) The superficial ventro-lateral fasciculus also contains fibers ascending to the cerebellum. Descending fibers from the cerebellum, together with large numbers of those connecting the different levels of the cord with one another, are found in the lateral fasciculus (3). (4) The lateral cerebrospinal fasciculus is the descending tract from the cerebral hemispheres to the motor cells, being the path of voluntary motor action. These tracts cross in the brain so that the right tract of the cord is connected with the left hemisphere and vice versa.

The ventral funiculus includes two fasciculi. The ventral fasciculus consists chiefly of fibers connecting the lateral halves of the cord and its different levels with one another. The small ventral cerebrospinal fasciculus contains descending fibers from the hemispheres, most of which cross through the white commissure to connect with motor cells on the opposite side of the cord. Some, like the fiber shown in the figure, may have crossed at a higher level in the cord. Such fibers as cross in the cord are believed not to cross in the brain so that all the motor cells are thus in communication with the opposite hemispheres of the brain.

The ependyma is that part of the neuroglia which lines the central canal. It appears like a simple cylindrical epithelium but the cell-like bodies are the ends of strands which may extend clear across the spinal cord to the external limiting membrane. A nucleus is generally found in the strand near the central canal; there may be others further away. Although in the embryo strands from the central canal to the periphery are easily traced, in the adult these are largely broken up, giving rise to cells with chief processes either to the periphery or to the central canal; if the radial strand is lost on both sides, stellate neurolgia cells result. These are shown in Fig 148. (The figure also shows the neuroglia cells with concentric fibers characteristic of the central gray substance, and a

From the substantia gelatinosa of a newborn rat.

Neuroglia cell of the white substance, from a cat 6 weeks old.

Fig. 14S.--NKLROGLIA Cklls from thk Spinal Cord. X 280.

Neuroglia cell of the gray substance of the base of the posterior column of a human embryo.

neuroglia strand with very numerous delicate processes from the substantia gelatinosa. These processes are said to be transformed into a granular substance. The gelatinous substance contains a few very small nerve cells, a network of fine nerve fibers and occasional stellate neuroglia cells.) The ependymal cells at birth and for some time afterward possess cilia projecting into the central canal. In the adult they have disappeared. It is questionable whether or not they arc motile. Single bodies but not diplosomes have been found at their bases. They have been considered to be more hke the cilia of the epididymis than like those of the trachea. The neurone theory. Years ago it was thought that the central nervous system was a continuous network of fibers, prolongations of which formed the peripheral nerves. The dorsal root fibers joined it on entering the cord and the motor fibers arose from it; between the two was a diffuse net. In opposition to this conception, the neurone theory set forth that the nervous system is composed of distinct cells, the neuronesy which are related to one another by contact and not by continuity. Some even supposed that the nerve fibers were retractile and by breaking their contact produced unconsciousness. In recent years when the syncytial nature of many tissues has been shown and fibrils have been found passing from cell to cell in smooth muscle (?), neurogha, and some epitheha, it has been reasserted that there is fibrillar continuity between nerve cells. The idea that the nervous system is an intercellular network with formative or nutritive cells appended to it, perhaps comparable with the elastic network in connective tissue, is now rejected. Peripheral fibers are not found to develop by the anastomosis of chains of cells. It is probable but not certain that the connection between nerve cells is merely by the contact of pericellular nets and of spiral terminal fibers wound about the cell bodies.

Vascular Tissue

The vascular tissues include the blood vessels and the lymphatic vessels, together with the blood and the lymph.

Blood Vessels


In an early stage the blood vessels of the embryo form a network in the splanchnopleure. In mammals, as in the chick

(Fig. 20, p. 21), the portion of the net nearest the median Une forms, on either side of the body, a longitudinal vessel, the dorsal aorta. The part of the net folded under the pharynx constitutes successively the vitelline veins, the heart, and the ventral aortae continuous in front of the pharynx with the dorsal aortae. The heart first appears as two dilated p'G- ^49. vessels, one on either side, which are

Blood vessels from a ral)bit embryo of 13 days,

developing as endothelial sprouts (en) from parts of the general uetwork. They

pre-existing vessels (b.V.); b.C, blood corpus- 10 ^

cie within a vessel. are brought together in the median

line under the pharynx and fuse. At first the heart pulsates irregularly, but with the estabUshment of the circulation, its beats become rhythmical. The blood flows from the net through the veins to the heart, and thence through the arteries back to the net. (AH of the future vessels of the body are believed to be offshoots from the endothelial tubes just described.j They grow out, as shown in Fig. 149, through the mesenchyma with which they are 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 vessel or from other vessels and fuse with them. Through the I anastomosis of such sprouts, networks of vessels of small caliber are produced which have been divided into two types, the sinusoid and capillary types. "" "

Sinusoids are formed as branches or subdivisions of a single vessel. A vein passing near a developing epithelial organ may send out branches over its surface, and if the organ itself is a ramifying structure its subdi\isions may be nearly enveloped by these venous branches. The liver

Fig. 150. Diagram Showing on the Lkft the Liver and its Sinusoids; on the Right the

Pancreas and its Capillaries.

The connective tissue is represented by dots. Ar., Artery ; Int., intestine ; Y., veins ;

Y. C. I., vena cava inferior; Y. P., portal vein.

is related in this way to the vitelline veins (in which the umbilical veins later come to empty). In the left portion of the diagram. Fig. 150, the liver is shown in heavy black as a branching outgrowth of the intestine. The portal vein (V. P.), which is a persistent part of the vitelline veins, forms a net of small branches, the endothelium of which is quite closely applied to the hepatic tissue. A thin but important layer of connective tissue intervenes, which could not be shown in the figure without great exaggeration. The subdivisions of the portal (vitelline) vein are the sinusoids and they come together to join the inferior vena cava, this part of which is also persistent vitelline vein. A relatively small hepatic artery later supplies the connective tissue around the ducts of the liver, but the essential vascular system of the liver'is a single large vein which has been resolved into a net of sinusoids. (In the human adult, this is perhaps the only instance of sinusoidal circulation. In the embryo the mesonephros (a renal organ of large size) is supplied by sinusoids derived from the posterior cardinal veins; the musculature of the heart grows into the cavity of the ventricle in plates and columns covered with endothelium (Fig. i6o), thus producing a net of vascular spaces or sinusoids. Although the sinusoidal circulation persists in these organs in lower vertebrates, such as the frog, it is not retained in man. The sinusoids of the heart are reduced to shallow spaces between the columns of muscle seen on its inner surface, and those of the mesonephros disappear with the transformation of that organ into the epididymis and epoophoron in the male and female respectively. Thick walled subdivisions which may occur in the course of a vessel' are not sinusoids. (The latter have essentially the structure of broad capillaries, from which they differ in that they arise from a single vesseL They are therefore wholly venous or wholly arterial

^ (papillary circulation arises by the union of vascular outgrowths from two vessels, the blood in which flows in more or less opposite directions, in other words, from an artery and a veln. The vessels to the lungs are at first a slender bhnd branch from a part of the aorta, and another blind outgrowth from the left atrium [auricle] of the heart. These extend through a column of mesenchyma to the epithelial ramifications of the lung, over which they branch and become united. The blood flows to the lung through the pulmonary artery passes into capillaries and returns to the heart through a vein. A similar circulation is shown in the diagram. Fig. 150. It is essentially an arttrio- venous circulation. From their jnode of development, capillaries have more connective tissue around them than the sinusoids.

is a round encapsulated knot of small subdivisions of an artery which reunite before leaving the capsule, and soon after form capillarie^ Glomeruli occur in the kidney and mesonephros. They are probably to be regarded as encapsulated capillaries rather than as sinusoids.

All the blood vessels of the young embryo, including the aorta and the heart, are merely endothehal tubes. Capillaries and certain sinusoids retain this structure in the adult, but the larger vessels have thick walls formed by transformation of the surrounding mesenchyma. The wall of the larger vessels consists of three coats or layers; the tunica intima, which is the endothelium with a thin layer of elastic connective tissue; the tunica media j which is chiefly smooth muscle with elastic substance intermingled; and the tunica externa [adventitial which is a dense layer of elastic connective tissue sometimes containing muscle.' In the heart the intima is called endocardium; the media, myocardium; and the externa, which there is covered with the pericardial mesothelium, is the epicardium. Capillaries, arteries, veins, and the heart will be described in order.


Fig. 151. Capillary from the Tail OF A Tadpole. Silvf.r Nitrate Preparation. (After Koelliker.)

Capillaries are endothelial tubes of varying diameter, the smallest being so narrow that the blood corpuscles are distorted in passing through them in single file. Their walls are composed of elongated, very flat cells with irregularly wavy margins as shown in Fig. 151, from a silver nitrate preparation. Between the cells the corpuscles, both red and white, may make their way out of the vessel. There are no preformed openings for this purpose, and the endothelial cells come together after the corpuscles have passed out. Two cells form the circumference of small capillaries, 4-5 to 7 ti in diameter, and three or four cells bound the larger ones of 8 to 13 /i. Nerves end in contact with them and it is possible for the endothelial cells to contract. The bulging of their nuclei into the lumen of the vessel, often seen in specimens of capillaries and of larger vessels, is probably an artificial appearance. The lining in life is thought to be smooth. Certain endothelial cells are said to be phagocytic, devouring objects which float in the blood, and some endothelial cells have been described as becoming detached and entering into the circulation small capillaries divide without decrease in caliber, and by anastomosis with neighboring capillaries they form networks differing widely in the size of the meshes. The closest meshes occur in the secretory organs and in the lungs and mucous membranes; the widest are in muscles, the serous membranes and the sense organs. The close networks consist of capillaries of large caliber ; and those with wide meshes are formed of more slender vessels. Thus the blood supply of glandular organs is particularly abundant. The sinusoids of the Uver are close meshed and large. )

Arteries, in approaching their terminal branches, become small {arterioles) and as * precapillary vessels' pass without line of demarcation into capillaries. The smallest arteries are endothelial tubes encircled by occasional smooth muscle fibers. In Fig. 152, 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 meshes 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 endothehum which with a dehcate elastic membrane beneath it constitutes the intima, is not seen, being out of focus. The nuclei of the media and externa are evident.

Fig. 152. S.MALL Arteries of Man. Nuclei of endothelial cells ; m, nuclei of circular muscle fibers, at m' seen in optical cross section ; a, nuclei of connective tissue. In A, since the endothelium is out of focus, its nuclei are not seen. X 240.

The structure of the larger arteries is illustrated by the cross section, Fig- 154- The intima consists of endothelium resting on a layer of connective tissue containing flattened cells and a network of fine elastic fibers.

Endothelial cell. Indentations made by smooth muscle fibers.

Fig. 153. Endotheliim of thh Mesenteric Artkry ok a Rabbit. Surface View. X 260.

The meshes of the fibrous and elastic tissue are elongated lengthwise of the vessel and on surface view they present a longitudinally striped appearance. Toward the media, the intima contains a conspicuous inner elastic membrane which is fenestrated and usually thrown into longitudinal folds. (Fenestrated membranes have been described on page 42.) In the smaller arteries (those under 2.8 nun. in diameter) the endothelium rests directly upon the inner elastic 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 subendotheUal connective tissue is said to be lacking. The inner elastic layer is very thick in the larger arteries of the brain, and may be double.

In the media the number of layers of circular smooth muscle fibers increases from the precapillary vessels which have but one, to large arteries Uke the brachial which have many. ( Sometimes the media near the intima contains a few longitudinal fibers7\ these have been reported in the subclavian, splenic, renal, and dorsalis penis arteries, and in the umbilical arteries they form a considerable inner layer. They are said to occur especially near the places of branching, c Between the circular muscles there is a varymg amount of connective tissue with wide meshed nets of elastic fibers, (^he proportion between the muscle and elastic substance varies^grgg^yjT^n the aorta and pulmonary arteries the elastic tissue far surpasses the muscular, and it predominates also in the carotid, axillary and common iliac arteries. Muscular tissue is ascendant in the distal arteries. The former group of vessels contains the conducting arteries, which always remain freely open; the latter are distributing arteries which by changing their caliber control the blood supply in their areas of distribution.^) After death these vessels contract, the muscle nuclei becoming spirally twisted, and the intima thrown into longitudinal folds. The blood is forced on into the capillaries and veins. Then as the rigidity of the muscles passes off, the elastic tissue distends the vessel which remains comparatively empty of blood; for this reason the ancients supposed that arteries contained air. The umbilical arteries are exceptionally deficient in elastic tissue and remain contracted, which aids in preventing haemorrhage when the umbilical cord is ruptured at birth.

Fig, 154. Portion of a Cross Skc 1 ion ok thk Brachial Artkry of Man. 'X 100.

The externa consists of connective tissue, which is denser and contains more elastic fibers in its inner portion. A prominent layer of elastic tissue near the media is called the outer elastic membrane, and is especially well developed in the carotid, brachial, femoral, coeliac, and mesenteric arteries. It is absent from the basilar artery and most of those within the skull. Sometimes the externa contains scattered bundles of longitudinal muscle. In the larger vessels it contains small nutrient blood vessels, the vasa vasorum. These may Endoiheiium. penetrate the outer

part of the media. Lymphatic vessels often accompany the blood vessels and have branches in the externa. Their deeper penetration is doubtful, although they have been reported in the intima of certain large vessels. Sensory nerves may terminate in the externa with free endings or in lamellar corpuscles, the latter being numerous in the abdominal aorta; free sensory endings are also found in the intima. (Thevaso-motor nerves are non-medullated sympathetic fibers which form plexuses in the media and terminate in contact with the muscle fibers. These plexuses are said not to contain ganglion cellsT)

The largest arteries, the pulmonary and the aorta (Fig. 155), have a broad intima which increases in thickness 'wnth age. It consists of an endothelium of cells less elongated than those of smaller arteries, resting on fibrillar connective tissue with flattened round or stellate cells. Its elastic fibers are broader toward the media, but there is no distinct inner elastic membrane. The media consists of very many concentric elastic lamina connected with one another across the muscle layers which lie between them, by elastic bands, ^he muscle fibers of the inner portion have been described as short, broadand flattened elements joined to one another so that they resemble cardiac muscle (Fig. 156). The outer muscle is of a more ordinary form. The elastic elements greatly predominate and on section the fresh aorta appears yellow, not reddish like smaller vessels?) The externa contains no outer elastic membrane. It is relatively and absolutely thinner than the externa in some medium sized arteries.

Fig. 155. From a Cross Section of the Thoracic Aorta of Man. X 100.


The veins have thinner walls, containing less muscle and less elastic tissue than the corresponding arteries. Since the artery to any structure and the returning vein often are side by side, it is frequently possible to make such comparisons in a given specimen. Because of thinner walls the veins often collapse, or at least are not as circular as the arteries; they may be distended with blood, and frequently have a larger lumen than the contracted artery, in many large veins the media is very thin or even absent, and the externa, containing large bundles of longitudinal muscle fibers, becomes the principal muscular coat

Fig. 156. Branch HD Smooth Muscle from thk Thoracic Aorta of a Child at Birth (a) AND AT Four Months (b). (After Koeliiker.)

Fig. 157. Part of a Cross Section of a Vein from a Human Li.mb. x 230.

The elastic elements are drawn very black. 1. Intinia ; 2, media ; 3, externa. (The middle of the 3 objects labelled nuclei of smooth muscle is apparently an elastic fiber.)

Venules and precapillary veins are wider than the corresponding arteries. Their endothelial cells are less elongated; the muscle fibers do not form so compact a layer and their nuclei are oval rather than rod shaped. For some distance from the capillaries muscle fibers are absent although encircling bundles of connective tissue may be present.

In the larger veins (Fig. 157) the intima consists of an endothelium of polygonal cells resting on connective tissue and bounded by the inner elastic membrane. The latter is structureless in small veins but is represented by elastic nets in the larger ones. In the intima of various veins occasional oblique or longitudinal muscle fibers have been found. (These 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 is best developed in the veins of the lower extremity (especially in the popliteal), less developed in those of the upper extremity, and still less in the larger veins of the abdominal cavity.) It consists of a circular muscle fibers, elastic networks, and fibrous connective tissue, the last being more abundant than in the arteries. In many veins the media

is represented only by connective tisiiitima. nwge sue, as in the superior vena cava and Media. I principal tributaries; the veins of

Externa with loiiKitu-l ) the retina and of the bones; and

diiial smooth muscle (WaXwrtfi

fibers cut across. | ^i' !2 those of the pia and dura mater.

Thin walled veins of large diameter

Fig. 158. Part of Cross Section of the Human Renal Vein. X 50. m the dura and elsewhere are called sinuses the externa of veins is their most highly developed layer It consists of crossed bundles of connective tissue, elastic fibers, and longitudinal smooth muscle which, as in the trunk of the portal vein and in the renal vein (Fig. 158), form an ahnost complete muscle layer. The blood and nerve supply of veins is similar to that of arteries. The vasa vasorum are said to be more numerous in veins, into which they empty.

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 thej^ appear like the valves of the lymphatic vessel shown in Fig. 164. (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 .J The valves do not occur in small veins. They are most numerous in "the veins of the extremities, but appear also in the intercostal, azygos and spermatic veins. Elsewhere they are absent. The endothelial cells on the surface of the valve toward the lumen of the vein are elongated parallel with the current, but on the side toward the wall of the vein they are transversely placed. Under the former there is a thick elastic network; the transverse cells rest on a delicate fibered connective tissue.

The Heart


The heart has already been described as a median longitudinal vessel beneath the pharynx, formed posteriorly by the union of the vitelline veins and terminating anteriorly in the ,two ventral aortae. Such a heart from a rabbit embryo is shown in Fig. 159, A. It soon becomes bent like a U, the venous opening being carried forward dorsal to the aortic part as shown in B and C. , The ventral or aortic limb of the U at the same time is carried to the right of the median plane (C). The dorsal limb is divided into two parts by an encircling constriction, the coronary sulcus (s, c). Its thick walled portion ventral to the sulcus is to form the ventricles of the heart; the thin walled dorsal portion becomes the cUria [auricles]. 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 connect 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.

Fig. 159. Embryonic Hearts. A and B, From rabbits 9 days after coitus ; C. from a human embrso of 3 (?) weeks ; D and E, from a 12 mm. pig (D sectioned on the left of the median septum, and ton the right of it) ; F, from a 13.6 mm. 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. 8., coronary sinus; f. 0., foramen ovale; I. f.. interventricular foramen; I. a., left atrium; p. a., pulmonary artery; p. Â¥., pulmonary vein ; r. a., right atrium ; 8. c, coronary sulcus; v., ventricle; ». b., Dicuspid valve ; V. t., tricuspid valve ; v. v., vitelline vein ; v. v. 8., valves of'the venous sinus.

In the heart of a 12 mm. pig embryo the septum has formed (Fig. 159, 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 oval e. (The figure shows the blind sprout of endothelium (p.v,) growing from the left atrium to form the pulmonary veins.) Between the left atrium and ventricle the median septum forms a flap-like fold; this and a similar fold from the outer waU of the heart constitute the bicuspid valve [mitral]. The median septum between the ventricles is never complete. It leaves an intervetUrictUa r foramen through which blood passes to the root of the aorta, which 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 across its lumen. 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 arteries has extended so that it joins the interventricular septum, and causes the interventricular foramen to open into the root of the aorta only (s).

The figures E and F further show that the veins which empty into the right auricle unite to form the venous sinus just before terminating. The outlet is guarded by a valve with right and left flaps. The left is said to assist in the closure of the foramen ovale, which occurs at birth, and leads to the formation of the fossa ovalis of the adult. The right flap of the venous sinus forms the valve of the vena cava [Eustachian valve] and the valve of the coronary sinus [Thebesian valve]. The coronary sinus ^ Fig. 159, F, c.s, is the persistent terminal portion of a vein which conveyed the blood from the left side of the embryo to the right atrium. . Most of its branches are lost by anastomosis with other vessels so that in the human adult its territory is h'mited to the heart itself. It is found in the coronary sulcus. Between the right auricle and ventricle is the tricuspid valve, similar to the bicuspid in its development. These valves are seen in section in Fig. 160.

(Embryologically the heart is composed of three layers, the endothelium, mesenchyma, and mesothelium^ The endotheUum is continuous with that which lines the blood vessels. The mesenchyma which surrounds it, becomes in part differentiated into connective tissue which with the endothelium makes the endocardium. In part it forms cardiac muscle, the myocardium, together with the tendinous rings {annuli fibrosi) between the atria and ventricles. As fibrous connective tissue it extends into the valves, and in looser form it unites with the mesothelium to make the epicardium. The epicardium or visceral pericardium is continuous with the' parietal pericardium in such a way that the two layers form a closed sac which envelops all of the heart except its base, where the large vessels enter and leave it. The pericardial cavity within this sac was originally continuous with the peritonaeal cavity, and in .the adult the walls of these subdivisions of the coelom have essentially the same structure. It contains the serous pericardial fluid.

Adult structure of the heart. The endocardium is a connective tissue layer covered with an endothelium composed of irregularly polygonal cells. It contains some smooth muscle fibers, and elastic networks which, in the atria especially, form fenestrated membranes. In the deeper part of the endocardium, partially developed cardiac muscle fibers occur in some manmials, but rarely in the human adult. Such muscle fibers, characterized by containing only a peripheral ring of banded fibrils, are called 'Purkinje's fibers'. They may be transformed into typical cardiac muscler The^Yalyes . of *. the heart are essentially folds of endocardium containing dense fibro-elastic tissue continuous with the annuli fibrosi.

In the atrioventricular valves there are smooth muscle fibers, most abundant near the attached borders; and some blood vessels. The semilunar valves of the pulmonary artery and aorta consist of connective tissue which is denser and more elastic on the side toward the^ ventricles, and particularly at the periphery and nodules of the valves. The nodules are thickenings in the center of the circumference of each segment of the valve, which perfect their approximation when closed.^ The endocardium contains free sensory nerve endings, associated with modified connective tissue cells, and undoubtedly motor nerves to its few muscle fibers. Lymphatic vessels have been described in it, together with the terminal capillaries of the epicardial blood vessek. The capi llaries of the Jieart are derived from venous outgrowths of the coronary sinus ^hich^unite in the epicar* dium with arterial outgrowths from the root of the aorta. The branches of these vessels invade the myocardium where they form abundant capillary networks and finally reach the endocardium. Some of them, especially in the right atrium, empty into the cavities of the heart as small veins, the venae minimae [of Thebesius]. Since imder certain conditions the blood may flow from the heart cavity to the myocardium through these vessels, they are of considerable importance. Their embryological history is unknown, so that nothing can be said concerning their possible relation to the sinusoids.

Fig. 160. Section of the Heart shown in Fig. 72, ca., Capillaries ; en., endothelium ; I. a., left atrium ; I. 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 ; v.t., tricuspid valve ; v. v. s., valves of the venous sinus.

The myocardium consists of cardiac muscle, the structure of which has been described on pages 81-85, together with intervening connective tissue, poor in elastic elements but containing many capillaries, motor nprve fibers, and tissue spaces. Some lymphatic vessels pass through it. The musculature of the atria is not completely separated from that of the ventricles; there is an uninterrupted portion in the median septum. An outer oblique layer of muscle covers both atria extending from one to the other. Each has a separate inner layer of longitudinal bundles, which, as foimd in the prominent ridges seen in the interior of the right atrium, are called pectinate muscles. There are similar but less prominent structures in parts of the left atrium. Besides these two layers, more or less definite, there are irregularly placed cardiac muscle fibers, and some which extend over the terminal parts of the large veins. The annuli fibrosi serve for the attachment of the ventricular muscles. The right annulus is larger than the left. Similar bands of fibrous tissue surround the openings of the arteries. The complex muscle layers of the ventricle may be separated by maceration into bands which arise in the annuli, wind spirally around the heart, and terminate in the opposite ventricle. The deeper layers pass through the septum and are arranged in 8 or S shaped figures. Muscular elevations projecting into the ventricles are called t rabeculae c ameae if columnar, or capillary muscles if conical. The latter may be connected with the margins of the cuspid valves by fibrous prolongations, mostly non-muscular, named the chordae tendineae. These structures represent the trabecular framework of the embryonic heart.

The epicardium consists of the single layered, very flat mesothelium and the underlying layer of connective tissue, which contains groups of fat cells. Its elastic fibers are continuous with those in the externa of the large veins, but they cannot be traced beyond the roots of the aorta and pulmonary artery. The epicardium contains lympathic vessels, the main branches of the coronary blood vessels, and important nerves.

The nerves to the heart are the cardiac nerves from the cervical sympathetic ganglia, and certain branches of the vagus. Together these form the cardiac plexus with the associated cardiac ganglion [of Wrisberg] at the base of the heart?) Their fibers extend in plexuses containing groups of cell bodies, over the dorsal walls of the atria, along the coronary sulcus, and over the ventricles where, however, cell bodies are less numerous. They lie in the epicardium but extend into the myocardium and appear as bundles of non-medullated fibers. A few medullated fibers, supposed to belong chiefly with sensory nerves, are found with them. Free sensory endings, comparable with those in tendon, are numerous in the epicardium and occur in the connective tissue of the other layers. They include vagus fibers, which also terminate in baskets around the cell bodies in the plexuses, but none are believed to pass directly to motor endings. The motor terminations belong with gangUon cells in or near the heart. Fibers from the cervical sympathetic ganglia may end in pericellular baskets like the vagus fibers, or may pass directly to the muscles. Their exact termination is not known.

Lymphatic Vessels

The lymphatic vessels are widely distributed through the body and physiologically they are perhaps quite as important as the blood vessels. They are however far less conspicuous. For this reason they are often neglected by the student, who with some study should be able to find them in a large proportion of the specimens examined. In a rabbit embryo of 14 days and i8 hours. Fig. i6i, the lymphatic system consists of several spaces in close relation with the veins, lined with endothelium like that of the blood vessels. The largest sac half encircles the internal jugular vein and sends a considerable branch into the deep connective tissue of the neck. Another large lymph space is near the renal veins; smaller ones are with the mesenteric vessels, the azygos, and the external mammaiy veins, on exam inatipn of younger embryos indicates that these Iymphatic vessels are detached branches of the adjacent vein^ (They are closed" endothelial tubes wliich send out ramifying branches mto the subcutaneous and other connective tissue, where they anastomose with one another or end blindlyT^They do not anastomose with the blood vessels, which they resemble, except for thinner walls and larger lumen. All of the lymphatic stmctures in the rabbit of 14 days become connected with each other and with similar new lymphatic vessels so as to form a system which empties into the veins at two points, namely, into the subclavian veins near the internal jugulars, on either side of the body. These openings have been described as persistent original connections of the lymphatic vessels with the veins but they cannot be delected in the rabbit figured; they may be formed later when the lymphatic system is essentially complete* In the adult the lymphatic vessels from the legs follow the femoral, hypogastric and common iliac vessels to the aorta, in front of which they form a network. Here they are joined by lymphatics from the viscera, notably from the intestines. The latter vessels were called lacteals from their milky appearance when filled wnth fat obtained from the alimentary canaL The net is continued into the thorax as one large vessel, the tkoracic duck wjhich may or may not be enlarged at its origin, forming the cist em a chyli. " The thoracic duct receives intercostal branches; in places it irregularly resolved into several small vessels which reunite. Near its termination in the left subclavian vein the thoracic duct receives subclavian and jugular trunks from the left arm and left side of the head On the right side there is a right lymphatic duct formed by the union of vessels from the right arm, the right side of the head and heart, and the right Iimg. Sometimes the thoracic duct bifurcates in the thorax sending a branch to the right lymphatic duct, or its main stem may be on the right side. Instead of a single opening of each dtict into the vein, there may be two or more, from its development the lymphatic system is a part of , ! the venous system, consisting of endotheUal tubes ramifying in connective tissue, anastomosing with each other or ending blindly. Its striking characteristic is that it is wholly afferent; it is like a venous system which has no corresponding arteries. The fluid ! within it is derived from the intercelluJ lar tissue fluids?)

Fig, Lymphatic Vksski s anp VtttNs tN a KAfi^it op

The lymphatlei are hrflvily »hadirii^i being aloni^ the Irft vag'us tuerveatid f sloDK the aorta. The siiVjcJavian vtin is futnicd hs the udIqn of the primitivcr ulnar, Pr, Ui., anil exicnijil mammary veins, Ex.M. The mhcr veins .ir« l InJ* Eiiid Ek. J., intttnal teSOeCtivelVH and pxtcf tia1)ujrutairf< , Ci., cciihaliL? ; Ai., as^ygos ; V.* vitelline; '"^ ^

6«fgaUrtc: S. H^, »up45Tiur mesenicfic; R. i.^ renat »na£ionii>si& rrtial vein); V. C- 1^ iiikxior vena cava; F*., femoral

A«. T., anterior tibial ; Pr* FK, pt\ cannccl with the femora! vein

iiiit.iv« fibuJar ; €. bp, brancb tci

Fig. 162. Connective tissue from the submucous layer of the small intestine of a cat, showing one blood vessel, b. v.; three lymphatic vessels, I. v.; and numerous intercellular spaces, I. s.

The smaller lymphatic vessels may be studied advantageously in sections of the small intestines from animals in which, intestinal digestion is in progress. The lymphatics are then dilated. They appear as spaces in the connective tissue (Fig. 162) which are sharply defined, thus contrasting with the intercellular

spaces. Their distinct lining is due to endothelium, the nuclei of which are often seen. Theyjiaye the structure of capillaries but are pf larger siz e; blood vessels o f £rriilax.caillb^r have, thicker walls. The lymphatic vessels often appear empty or contain a granular coagulum, whereas red blood corpuscles are to be expected in the blood vessels. A structure containing many red corpuscles may be safely regarded as a blood vessel, but obviously an empty vesseHsxby no means a lymphatic. Occasional red corpuscle find their way into lymphatic vessels. In silver nitrate preparations (Fig. 163) the lymphatic endothelium is seen to be similar to that of the blood vessels. Valves are numerous even in small lymphatic vessels. They are folds of endothelium such as would result if the distal part of proximal part. The vessels are often distended on the proximal side of the vessel were pushed forward into the the valve, as may be shown in injected specimens especially. One of these swellings is shown in Fig. 163. The valves of a larger lymphatic vessel appear in Fig. 164.

Fig. 163. Silver Nitrate Preparation of a Lymphatic Vessel from a Rabbit's Mesentery, Showing the Boundaries of the Endothelial Cells, and a Bulging Just Beyond a Valvk.

Fig. 164. 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.

In lymphatic vessels having a diameter of 0.2-0.8 mm. or more, three layers may be distinguished very similar to those of thin walled veins. The intima consists of endothelium and connective tissue containing delicate elastic nets with longitudinal meshes. The media has circular smooth muscle and but little elastic tissue. The externa has bundles of longitudinal muscle fibers, and similarly arranged connective tissue. The nerve supply is like that of the blood vessels.

Although the present tendency, baied upon the similar results of several investigations, is to make a sharp distinction between tissue spaces and lymphatic vessels, it should be noted that these have long been regarded as inseparable.

Some authorities still consider that the lymphatic vessels open freely at their distal ends and blend with connective tissue. Lymphatic vessels have also been

I described as opening into the peritoneal cavity and other parts of the coelom through definite mouths or stomala. The stomata are thought to be artificial.

^The endothelium remains entirely separate from mesothelium so far as is known


Blood consists of rounded cells entirely separate from one another floating in an intercellular fluid, the plasma. The plasma also contains fragments of cells called blood plates or platelets, together with smaller granular bodies. The blood cells or corpuscles are of two sorts, (i) red corpuscles (erythrocytes) which become charged with the chemical compound, haemoglobin^ and which lose their nuclei as they become mature; and (2) white corpuscles (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 superposed layers of the haemoglobin-filled red corpuscles. Thin films of blood, like the individual red corpuscles as 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.

Red corpuscles

The first cells in the 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 chromatin network with several coarse chromatin masses. Haemoglobin 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. Meanwhile the nucleus becomes smaUer and so dense as to appear a structureless mass, stained nearly black with haemotoxylin. This transformation of the cells is shown in Fig. 165. Cells which are destined to produce red corpuscles are called eryihroblasts, especially in the stages with reticular nuclei. The later stages when the cells are smaller and have dense nuclei are called normoblasts. The nuclei of normoblasts have been seen to be extruded as in Fig. 165. Before they disappear they may become mulberry, dumb-bell, or trefoil shaped, (as in the group in the lower left hand comer of Fig. 174, p. 152) or they may fragment into several dark masses. These are said to be extruded so that they lie free, outside of the cell, where they are devoured by phagocytes. On the other hand it is believed by some that extrusion never occurs as a normal process, but that the nuclei are dissolved within the cell. The question has long been discussed and is not settled. The loss of the nuclei begins in human embryos of the second month; at the third month nucleated corpuscles are still more numerous than the non-nucleated. At birth and afterwards it «, successive stages in the development of

fig. 165. the development of red

, erythroblasts, from a cat embrvo ; b, the unusual to find nucleated red corpus- extrusion of the nucleus in cat embryos.

cles in the circulating blood.

The erythroblasts at first divide by mitosis in the blood vessels everywhere. Later they gather about the sinusoids of the liver. Apparently they are not only within the blood vessels but also outside of them, in the reticular tissue between the endothelium and the hepatic cells. Red blood corpuscles both nucleated and non-nucleated are flexible bodies incapable of amoeboid movement; accordingly they pass out between endothelial cells less readily than the leucocytes. The emigration of red corpuscles is called diapedesis, (^ fetal life erythroblasts multiply not only in the liver but also in the spleen. Except in a fewmammals the spleen does not normally retain this function in the adult. XThe red bone marrow becomes the essential permanent location for the production of red corpuscles, and throughout life it contains the multiplying erythroblasts. In certain important diseases normoblasts leave the marrow and occur in the circulating blood, sometimes together with large forms having reticular nuclei, and called megaloblasts. The megaloblasts have been regarded as younger erythrocytes than the normoblasts.

With the loss of the nuclei the red corpuscles become smaller and^cup sh aped; they are convex on one side and concave on the other. ; (*BeQ shaped,' implying a flaring rim, is a less descriptive term; 'sauceF shaped,' signifying that they are often shallow cups, has lately been employed.) (The protoplasmic reticulum has disappeared and the mature corpuscle nas been said to be a drop of dissolved haemoglobin enclosed in a membrafie'.^ With special methods a granular network has been demonstrated

in some apparently homogeneous corpuscles. Others in the same preparation may contain no reticulum. The network has been interpreted as the remains of the original protoplasmic net, and also as an artificial decomposition of haemoglobin. It occurs especially in the newly formed corpuscles (seen in cases of anaemia). Instead of a net there may be rings or round bodies the nature of which is not clear. The_ existence of a m embrane around the corpuscles is still debated. It does not stain distinctly and seems to blend with its contents. Sometimes it is described as an exoplasmic, fatty layer. f¥he osmotic changes in the corpuscles show that they are surrounded by structures which are not composed of haemoglobin, and which act as membranes..

Fig. 166, Red Corpuscles. Sketched while circulating in the vessels of the Omentum of a Guinea Pig.

Fig. 167. Rko Corpuscles in Various Conditions.

Cup shaped corpuscles may be observed circulating in the omentum of a guinea pig. The etherized animal should be placed beside the stage of the microscope and the omentum spread over the condenser. A cover glass is put directly upon it, and the corpuscles are examined with an oil immersion lens. Some of them drawn freehand while they were under observation are shown in Fig. 166. If a drop of blood from the finger is spread upon a slide in a thin layer and examined ai once some cup shaped forms are seen. â–  They soon flatten into biconcave discs, appearing as in Fig. 167, A. Their thin centers appear light in ordinary focus, but become dark if the objective is raised (Fig. 167, C). The biconcave shape is apparent when a corpuscle is seen on edge (Fig. 167, B). This form of the red corpuscles is still ordinarily described as normal, since it is observed in freshly drawn blood. The making of the thin layer has, however, subjected the blood to very unnatural conditions. Very quickly the corpuscles arrange themselves in rows, or rouleaux (Fig. 173), such as are not found within the blood vessels. In TnosF" of the sections which the student examines, in preparing which various preserving fluids have been used, cup shaped corpuscles will be seen like those in Fig. 167, D. Often they will show irregular contractions and distortions (E). If the corpuscles are placed in a dilute fluid, their haemoglobin is dissolved out and water enters them. They become mere flattened membranes or shadows (Fig. 167, F). Such barely visible structures are sometimes found in urine. In dense solutions, or in ordinary fresh preparations as they begin to dry, water leaves the corpuscle, which shrinks, producing nodular, refractive masses of haemoglobin called crenated corpuscles (Fig. 167, G). A 0.6 %

1, Haemin crystals and 3, haemaloidin crystals from human blood ; 2, crystals of common salt (X 560) ; 4, haemoglobin crystals from a dog ( X 100).

aqueous solution of common salt is said to cause the least distortion from swelling or shrinkage. In life, corpuscles presumably change their shape with variations in the plasma and in the nature of the haemoglobin. A small number of spherical corpuscles is said to occur normally. When a drop of blood is heated to excess the corpuscles form small globules united by stalks or entirely separate. This indicates a viscid membrane, but does not prove the entire absence of membrane as has been asserted.^ In strong picric acid the corpuscles burst, discharging their contents through a rent in a capsule which may be largely due to the reagent.

Haemoglobin is an exceedingly complex chemical substance which combines readily with oxygen to form oxyhaemoglobin. 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. (JIaemoglobin may be dissolved from the corpuscles by mixing blood with ether, and upon evaporation it crystallizes in rhombic shapes which vary with diflferent anim^^ Those from the dog are shown in Fig. i68, 4; in man they are also chiefly prismatic. Haemoglobin is readily decomposed into a variety of substances, some of which retain the iron which is a part of the haemoglobin molecule; others lose it. Haematoidin, 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. i68, 2) may be found in old blood extravasations within the body, as in the corpus luteum of the ovary. Haemosiderin, which contains iron, appears as yellowish or brown granules sometimes extremely fine, either within or between cells. The iron may be recognized b](^ the ferro-cyanide test which makes these minute granules bright blue, (if dry blood from a stain is placed on a slide with a crystal of common sa3t-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 combination of a haemoglobin product with hydrochloric acid is formed, called haemin. It crystallizes in rhombic plates or prisms of mahogany brown color (Fig. 168, i). Such crystals would show that a suspected stain was a blood stain, but they aflFord no indication of the species of animal from which it was derived^)

The dimensions of red corpuscles are quite constant. Those in human blood average 7.5 ,« in diameter and ordinarily vary from 7.2 to 7.8 /i. They sometimes surpass these limits. In biconcave form they are about 1.6 fi thick. The cups average 7 /^ in diameter and are 4 /^ in depth. Spherical corpuscles are said to be 5 /i in diameter, ^^he 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 // in the dog, 7.48 // in the guinea pig), but the species of animal cannot satisfactorily be determined from the diameter of the corpuscles. It should be noted that the blood of amphibians, reptiks and birds, in the adult contains only nucleated red corpuscles which are oval discs more or less biaonvex. They are very large in amphibia (Fig. 169).

(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.

Leucocyte in motion ; at rest,

Side view of red corpuscles.

Fig. 160 Blood Corpuscles from a Frog. 4, 6, and 6, Surface views of red corpuscles, 6 after treatment with water. X 600.

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 eliminateH 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 marrowT) 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 haemolysis 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. Such studies are not histological, however.

The account of the mammalian red corpuscles may be summarized as follows. Erythroblasts with large reticular nuclei, cell membranes7 and a protoplasmic net, are the first blood cells in the embryo. They multiply by mitosis in the circulating blood, and most of them by acquiring smaU dense nuclei become normoblasts. Haemoglobin^ has meanwhile developed in their protoplasm which loses its reticulum. The membrane is no longer well defined. The nucleus after more or less fragmen- " tation becomes either absorbed or extruded from the cell, which thereupon is cup shaped. The cups are flexible and very susceptible to osmotic changes, swelling or shrinking with alterations in the density of the suf- ; rounding plasma. They are destroyed by dissolution or fragmentatioi^, ' and are often devoured by phagocytic cells. From them pigments with o^ I without iron are developed. The red corpuscles in the adult are formed j chiefly in the red bone marrow, and are destroyed especially in the spleei ! and haemolymph glands; some of their products are eliminated in the bile^ I

White corpuscles

The leucocytes are those blood cells which retain ; their nuclei and do not contain haemoglobin. About eight thousand occur in a cubic millimeter of human blood. If their number 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 I leucocytes may be divided into three classes according to nuclear characteristics, namely into lymphocytes, large mononuclear leucocytes, and polymorphonuclear leucocytes^

Lymphocytes are large and small. The ordinary small ones are about the size of red corpuscles, 4 to 7.5 /^ in diameter. Large ones may double this diameter. Their protoplasm forms a narrow rim, sometimes almost imperceptible, about the dense round nucleus (Fig. 170, 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 polymorphonuclear type. They form from 22 to 25 % of all leucocytes.

Large mononuclear leucocytes, sometimes 20 /^ in diameter, 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 nu

which is abundant, usually 

A B ^"' c lacks coarse granules or other

Fig. 170 Leucocytes as seen in a Section of HicHnrtivP fpatiir

Human Tissue Preserved with Zenker's Fluid. UlSlincuve leaiures. OOme A, Lymphocyte; B, large mononuclear leucocyte; C. three timeS it COntainS a fcW nCUtropolymorphonuclear neutrophiles. uiiica IL i.uuLcUii:> d lew IICULTU

philic granules to be described presently. These cells are notabW _ phagocytic. They form only from I to 3% of The leucocytes. In certain respects they are intermediate between lymphocytes and polymorphonuclear cells.

Polymorphonuclear leucocytes are cells somewhat larger than red corpuscles, being from 7.5 to 10 /i in diameter. They are characterized by having nuclei with irregular constrictions leading to an endless variety of shapes (Fig. 170, C). The nodular subdi\isions may be connected by broad bandsjor by slender filaments. /iFis said that in degenerating cells the nucleus is divided into several separate masses. Such unusual forms can properly be called ' polynucle ar,' 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 nud^' The irregular shape of the polymorphous nuclei has been ascribed to degeneration, comparable with irregularities in the erythroblast nuclei, and also to amoeboid changes associated with those of the cell body. It has been asserted that the nuclei become rounded when the cells are at rest. The latter explanation appears improbable. In the protoplasm a centrosome, or a group of its minute subdivisions, has been found in the concavity of the nucleus. (A^ dehcate cell membrane has been described, but membranes are usually considered lacking in all forms of leucocytes, <^ fundamental characteristic of polymorphonuclear leucocytes is the devel^ opment of distinct granules in their protoplasmT) These are more definite structures than occur in ordinary protoplasm,^ that lymphocytes together with the large mononuclear cells are^considered non-granular. Not only

Fig. 171. The Blood Corpusclks. (Wright's Stain.) (E. F. Faber, from Da Costa's Clinical Hematology.)

I, Red corpuscles. II, Lymphocytes and laree mononuclear leucocytes. Ill, Neulrophiles.

IV, fcosinophiles. *Y, Myelocytes (not found in normal blood). Yl, Mast cells.

do the granules differ in size but also in staining reaction as may be seen by employing the * blood stains.' A drop of blood is spread thinly on a cover glass and dried, afterwards being stained with a mixture of acid and basic dyes. The details of nuclear structure are not preserved, but the granules are clearly differentiated. With several of the blood stains the fine granules stain purple or lilac and the coarse ones are red in some cells and blue in others. Only one sort of granule occurs in a single cell. Figure 171 shows corpuscles from such a preparation.

Cells containing coarse blue granules, which often obscure the nucleus, are called m ast cells . (The German word mastj meaning food, was applied to them because of supposed nutritive functions.) They form about 0-5 % of the leucocytes in the blood. Along the blood vessels, especially in the mesentery, mast cells may be found in connective tissue if it is hardened in alcohol and stained with a basic stain Uke methylene blue. Zenker's fluid, a preservative often used, destroys these granulesT) (The mast celk of connective tissue are larger than those in the bloodTand generally have rounded nuclei. They have been said to arise independently of the "mast leucocytes.")

Polymorphonuclear cells with coarse granules which stain red with eosin, an acid stain, are called eosinophiles [oxyphiles, acidophiles]. They form from 2 to 4 % of the leucocytes m the blood, a proportion greatly increased in certain diseases. Eosinophilic cells occurring in connective tissue sometimes have round nuclei. It is questionable whether such forms are derived from the eosinophiles which migrate from the vessels.

The third type of granular cell, unlike the other kinds, contains fine

eianules, and these stain purple or hlac by taking both stains to some extent.

(They are called neutro philes and form 70 to 72 % of the leucoc3rtes 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^

The relation of the various leucocytes to one another has not yet been determined. The first forms which appear in embryonic blood have rounded nuclei and are perhaps intermediate between lymphocytes and large mononuclear leucocytes. They resemble the young erythroblasts from which they may be derived. \ Many authorities consider it probable that there is a common origin for all 'the blood cells.^(Like the red corpuscles the leucocytes in the adult are produced in tire meshes of reticular tissue outside of the blood vessels; the lymphocytes chiefly in the lymph glands, and the granular leucocytes chiefly in the red bone marrow where the red corpuscles also develop. " The lymphocytes appear in the circulation before the granular leucocytes. An investigator (Engel) of the blood in pig embryos found that well defined leucocytes similar to lymphocytes appeared first in pigs of 8 cms. Another investigator (Sabin) has recorded that in the lymph glands of an 8 cm. pig the lymphocytes are first recognizable. From these independent studies it seems that lymphoc3rtes appear in the lymph glands and in the blood at about the same time. "In the guinea pig there seems to be a connection between the time of the appearance of the polymorphonuclear leucocytes in the marrow and in the blood" (Jolly and Acuna). The granular leucocytes appear in the blood and in the marrow at first as cells with round nuclei. Such cells in the adult are found normally only in the marrow and are called myd&cytes. They enter the blood when their protoplasm is full of the granules which develop gradually, and when their nuclei are polymorphous. Only in disease are myelocytes and erythroblasts found in the blood of adults but they circulate normally in the blood of young embryos. The important question, whether the leucocytes arise directly from the mesenchymal tissues of lymph gland dud bone marrow, or from cells which have emigrated into them from the blood vessels, has not been determined. /

The large mononuclear cells with round nuclei are thought by some to be cells from which both lymphocytes and granular forms arise. The granules may be secretory products. Eosinophilic granules were once thought to be transformations of the neutrophilic, occurring in old corpuscles. Lately they have been regarded as the ingested fragments of red corpuscles, but the fact that they rarely, if ever, are mixed with neutrophilic granules is against this view. The form of granule seems to be determined by unknown factors early in the dijQFerentiation of the leucocytes, and to be fixed for a given cell after the first granules have appeared.

(In coimection with the terms applied to leucocytes it should be noted that those with basophile granules are not called basophiles as would be consistent, but mast cells?) The non-granular lymphocytes and large mononuclear cells are, however, sometimes called basophiles because their protoplasm takes a pale basic stain. This is undesirable. Mast cells were originally called plasma celis, a term now applied to oval cells derived from lymphocytes by an increase in their protoplasm (Fig. 49, p. 47). \They have eccentric nuclei, and their non-granular protoplasm stains deeply with basic dyes. Plasma cells occur in connective tissue, but probably not in the bloo^^they are of pathological importance.

The variefies of leucocytes may be reviewed as follows:

Lymphocytes, 22 to 25 % of the leucocytes, are small (about the szie ' 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. Eosinophils, 2 to 4 %y with coarse eosinophilic granules. Neutrophils, 70 to 72 %, with fine neutrophilic granules.

Fig. 172. Blood Plates beside A Red Corpuscle.

Blood plates

Blood plates or platelets are round or irregular protoplasmic structures, 2 to 4 // in diameter. From 245,000 to 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 stained with Wright's blood stain it appears that they have dark granular centers and clear peripheral zones (Fig. 172). They have formerly been interpreted as small nucleated cells, and as fragments of leucocytes. Dr. J. H. Wright has recently shown that they are fragments of elongated pseudopodia of the giant cells in the bone marrow. ) Their peripheral zone is ectoplasm and their inner granular part is endoplasm. Consequently they are non-nucleated. The giant cells are not always producing blood plates. Only certain of them show the pseudopodia, which have been observed extending into the blood vessels. In the blood the plates exist for some time, as they are found in clots several days old. The function of the plates is unknown. In drawn blood they rapidly adhere to one another forming masses, but not rouleaux. Sometimes they present irregular projections and so have been described as amoeboid. In the clotting of blood the plasma separates into a solid part, the fibrin and a thin fluid, the serum. The blood clot or thrombus consists of fibrin with the entangled corpuscles, a mass which contracts after it forms, squeezing out the serum. The fibrin is deposited (precipitated?) in slender threads which radiate from the blood plates and form nets shown in Fig. 173. Therefore the plates have been considered active agents

in the clotting of blood and. have been called thrombocytes. In the blood of amphibia, spindle shaped nucleated cells smaller than their red corpuscles possess adhesive properties and are also named thrombocytes. Since

Fig. 173. Red Corpuscles forming Rouleaux. Fibrin in Filaments Radiating from Blood Plates. (From Da Costa's Clinical Hematology.)

the plates have been shown to be fragments of giant ceUs they can scarcely be homologous with the amphibian thrombocytes.


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 haematokonia (or haemokonia). In ordinary sections the plasma appears as a granular coagulum.


The contents of the lymphatic vessels is called Ijmaph. It is a fluid which may contain the various cellular elements of blood in small numbers. Red corpuscles and pol)miorphonuclear leucocytes are occasional. L)maphocytes are the most abundant cellsj^and some of them have considerable protoplasm and are ghagocytic. (^The lymph fluid is not identical with plasma or with tissue fluids, yet all three are similar. 1 Nutrient material from the plasma traverses the tissue fluids to the epithehal cells, certain products of which pass back into the tissue fluids. They may be taken up by the blood or by the Ijrmph, first passing through the endothelial cells of the vessels. From the intestine much of the absorbed fat is transferred across the tissue spaces to the lymphatic vessels in which it forms a milky emulsion knoWn as chyle. £rhe small Ijmaphatic vessels containing it have been known as lacteals.) ' This example shows that lymph may exist in mor^ than one form. In the subclavian veins it mingles with the blood plasma.

In ordinary sections lymiph appears as a fine coagulum, containing a few lymphocytes, and occasionally other corpuscles.

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