Book - A textbook of histology, including microscopic technic (1910) Special Histology 3

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Böhm AA. and M. Von Davidoff. (translated Huber GC.) A textbook of histology, including microscopic technic. (1910) Second Edn. W. B. Saunders Company, Philadelphia and London.

A Textbook of Histology (1910): Introduction To Microscopic Technic | General Histology | I. The Cell | II. Tissues | Special Histology | I. Blood And Blood-Forming Organs, Heart, Blood-Vessels, And Lymph- Vessels | II. Circulatory System | III. Digestive Organs | IV. Organs Of Respiration | V. Genito-Urinary Organs | VI. The Skin and its Appendages | VII. The Central Nervous System | VIII. Eye | IX. Organ of Hearing | X. Organ of Smell | Illustrations - Online Histology
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Special Histology

III. The Digestive Organs

THE intestinal canal with the glands derived therefrom originates from the inner layer of the blastoderm, the entoderm. The latter, however, does not extend to the external openings of the body, as the ectoderm forms depressions at these points which grow inward toward the still imperforate fore and hind gut to communicate finally with its lumen. This applies as well to the formation of the primitive oral cavity, which is separated only secondarily into oral and nasal cavities, as to the anus. The anterior boundary between the ectodermal and entodermal portions of the digestive tube consists of a plane passing through the opening of the posterior nares and continued downward along the palatopharyngeal arch. Everything lying anterior to this is of ectodermal origin, therefore the entire oral and nasal cavities with their derivatives. The lining of these cavities consists, however, of a true mucous membrane, closely resembling in its structure that of the intestinal tract.

A. The Oral Cavity

The epithelium of the oral mucous membrane is of the stratified squamous type, differing from the epithelium of the epidermis in that the stratum granulosum does not appear here as an independent layer. The stratum lucidum is also wanting, and the cornification of the layer analogous to the stratum comeum of the skin is not complete (compare Skin). In the mucous membrane the cells of even the most superficial layers contain nuclei, which, although partly atrophied, still show chromatin, and as a consequence are easily demonstrated.

Beneath the epithelium lies a tissue of mesodermic origin, also belonging to the mucous membrane and known as the mucosa or stratum proprium (lamina propria, tunica propria), in which numerous glands are situated. The mucosa consists of a fibrillar connective tissue with few elastic fibers, and of adenoid tissue containing numerous lymphoid cells ; essentially, therefore, a diffusely distributed adenoid tissue with occasional lymph-follicles imbedded in its substance. The mucosa presents numerous papillae, which are either simple or compound (branched) elevations of the mucosa, varying in length and density, according to their location and extending for variable distances into the overlying epithelium. As in the papillary layer of the corium (see Skin), so also here the superficial layer of the stratum proprium contains very fine elastic and connective -tissue elements which contribute to the structure of the papillae. All these papillae contain capillaries and arterioles which are derived from an arterial network in the mucosa. The lymphatics are similarly arranged.

At the red margin of the lips the papillae are unusually high and are covered at their summits by a very thin epithelial layer (Fig. 1 80). Besides the sebaceous glands which lie at the angles of the mouth, and whose ducts open at the surface, there are here no other glandular structures. In the mucosa of the mucous membrane of the lips and cheeks the papillae are low and broad ; here also open the ducts of compound lobular, alveolar glands, the glandules labiales and buccales whose structure is similar to that of the large salivary glands (see these). The gums possess very long and attenuated papillae, covered by a very thin layer of epithelium, therefore bleeding at the slightest injury. That part of the gum covering the tooth has no papillae. The gums contain no glands. The papillae of the hard palate are arranged obliquely, with their points directed toward the opening of the mouth. The papillae of the soft palate are very low and may even be absent. They are somewhat higher on the anterior surface of the uvula. On the posterior surface of the latter occur ciliated epithelia distributed in islands between the areas of stratified squamous epithelium. In the soft palate and uvula are found small mucous glands.

Under the mucous membrane there is a layer consisting principally of connective tissue and elastic fibers, the submucosa (stratum submucosum, tela submucosa). In the mucous membrane of the mouth the transition of the tissue of the mucosa into that of the submucosa is very gradual. The submucosa of the hard palate is closely connected with the periosteum and contains, especially at its posterior portion, numerous glands. In other regions of the mouth (lip) the glands extend also into the submucosa. The mucosa and epithelium lining the mouth cavity are richly supplied with nerves which terminate either in special sensory nerve-endings or in free sensory nerve-endings, or on the bloodvessels. In the papillae of the mucosa are found corpuscles of Krause. (See p. 169.) The nerves terminating in free sensory endings are the dendrites of sensory neurones (medullated sensory nerves), which, while yet medullated, branch and form plexuses with large meshes, situated in the submucosa and deeper portion of vessels are richly supplied with vasomotor nerves, the neuraxes of sympathetic neurones, which terminate on the muscle-cells of the vessels. In the adventitia are also found free sensory nerveendings. (See Fig. 177.)

Fig. 180. Section through the lower lip of man ; X l & the mucosa. The medullated branches of the nerve-fibers constituting these plexuses proceed toward the epithelium, dividing further in their course. Immediately under the epithelium the medullated branches lose their medullary sheaths, divide further, and form the subepithelial plexuses. The nonmedullated branches enter the epithelium, where they form telodendria (end-brushes), the terminal branches of which surround the epithelial cells, between which they end either in very fine granules or in small groups of such, or, again, in variously shaped end-discs. (See Fig. 135.) The blood

1. The Teeth

The human dentition comprises twenty temporary or milk teeth, namely, above and below, four incisors, two canines, and four molars, which are replaced by thirty-two permanent teeth, consisting of four incisors, two canines, four premolars, and six molars for each jaw. Each tooth consists of a crown, which projects above the gums, a relatively short and narrowed portion known as the neck, and a portion which fits accurately into the alveolus and is known as the root. For the variations in shape which the different kinds of teeth present, the reader is referred to the textbooks of anatomy or to special works dealing with this subject.

Structure of the Adult Tooth. The adult tooth is made up of three substances the enamel, the dentin, and the cementum. The latter covers that part of the tooth within the alveolar process of the jaw and also the root of the tooth. The enamel caps that part of the tooth projecting into the oral cavity, the crown of the tooth. The neck of the tooth is the region where the cementum and enamel come in contact. The greater part of the tooth consists of dentin, which is present in the crown as well as in the root. All the substances of the tooth just mentioned become very hard from the deposition of lime-salts. Every tooth contains a cavity surrounded by dentin, the pulp cavity, or dental cavity. This is filled with a soft tissue, the pulp, consisting of white fibrous tissue, vessels, and nerves. That part of the pulp cavity lying in the axis of the fang is called the root-canal ; by an opening in the latter (foramen apicis dentis) the pulp is connected with the periosteal connective tissue of the dental alveolus.

The enamel is a very hard substance, the hardest in the body, and may be compared to quartz. In uninjured teeth the enamel is covered by an exceedingly thin, structureless membrane, the cuticula dentis or Nasmyth's membrane, which varies in thickness, measuring from 0.9 fj. to 1.8 //. It is very resistant to acids and alkalies. On its under surface it often shows small pits, into which project the ends of the enamel prisms. The enamel contains very little organic substance (from 3^ to 5^), in consequence of which it is soluble in acids with scarcely any residue. The elements composing it are prismatic columns, the enamel prisms, which probably occupy the whole thickness of the enamel from the superficial membrane to the dentin. They are slightly thicker at the surface of the tooth than at the dentin, and in transverse section show a hexagonal or polygonal shape, and measure from 3 /j. to 6 // in diameter. They often show quite regular transverse markings which express, however, no structural peculiarity, but are due to irregularities in the prisms. They are joined to each other by a cement-substance which is somewhat more resistant than the substance of the prisms themselves. In the adult they are entirely homogeneous, but in embryos and even in the new-born they show a (fibrillar) longitudinal striation. In their course through the thickness of the enamel they change their direction by a series of symmetrical curves, and f cross each other in groups in a typical manner. There are also seen in the enamel the parallel lines known as the lines of Retzius (see Fig. 181), which pass obliquely through the enamel and which are to be regarded as traces of the strata caused by the periodic deposition of limesalts ; they are very variable, as their structure depends on the nutritive condition during the deposition of the lime - salts (Berten). Another series of parallel or nearly parallel stripes or lines, known as Schrdgcrs lines, are also observed. Those in the lateral portions of the enamel have a direction nearly perpendicular to the surface. They are thought to be due to a difference in the refraction of the light, presented by bundles or layers of enamel prisms so disposed as to be cut in different directions. The dentin is, next to the enamel, the hardest tissue of the tooth. After decalcification it presents

a ground substance in which are found numerous very fine fibrils, which do not branch nor anastomose, and are in their behavior toward acids and alkalies like the fibrils of white fibrous (collagenous) tissue. They yield gelatin on boiling. The fibrils are separated by an interfibrillar substance, in which the mineral salts are deposited. The course of the fibrils is, in the main, parallel to the surface of the dentin. They are often grouped in small bundles (v. Ebner). The dentin is permeated by a system of canals having usually a transverse direction, the so-called dentinal tubules, which are from 1.3 fjt to 4.5 // in diameter. These originate in the pulp cavity, and during their course become slightly curved, like the letter S- The dentinal tubules usually present several dichotomous divisions near their origin, then pass to the outer third of the dentin without conspicuous divisions; here they again branch, becoming constantly smaller. In their course they give off numerous side twigs which

Fig. 181. Scheme of a longitudinal section through a human tooth. In the enamel are seen the "lines of Retzius."

Fig. 182. A portion of a ground tooth from man, showing enamel and dentin ; X 1 7 anastomose with those of neighboring tubules. The general course of these tubules is shown in figure 181. Certain of the tubules pass for a short distance into the enamel, where they are found between the prisms. In the human tooth the majority end just before reaching the enamel. In the root of the tooth they end near the surface, or in the interglobular spaces (see below), or, again, they may be joined to form loops. The dentinal tubules possess sheaths, the sheaths of Neumann, which may be isolated, analogous to the sheaths of the canaliculi of bone. They may be regarded as differentiated and more resistant ground substance. The dentinal tubules contain throughout their entire length filiform prolongations of certain pulp-cells (odontoblasts), the dentinal fibers. Peculiar, irregularly branched spaces are often seen in the dentin. These are the interglobular spaces of Czermak. They represent areas in which calcification has not taken place. Their number is variable ; when relatively small and numerous, they appear, in dry preparations seen under low magnification, as a granular layer the granular layer of Tomes.

The cementum is closely adherent to the dentin, and consists of bone tissue, the parallel lamellae of which contain, as a rule, no Haversian canals. There occur, however, cement lamellae, which in places lose their bone-cells. A peculiarity of the cementum is the presence of a large number of Sharpey's fibers, which are especially abundant in those areas containing no bone-corpuscles. These fibers are usually found in an uncalcified condition.

Fig. 183. A, Longitudinal section through a human molar from the center of the enamel layer, decalcified with dilute hydrochloric acid ; B, tangential, C, radiate, and D, transverse section through the dentin of a human tooth, showing the fibrillar structure of the ground-substance (taken from v. Ebner, 91) : a and b, Two layers in which the direction of the enamel prisms changes ; in c is seen a dentinal fiber with its sheath ; e, groups of fibrils ; d, dentinal tubules.

The tooth=pulp is a tissue resembling embryonic connective tissue, consisting of connective-tissue fibrils, branched connectivetissue cells, and a semifluid, interfibrillar ground-substance. It is characteristic of this tissue that the fibrils never join to form connective-tissue fibers. It is probable that the fibrils are similar to those of white fibrous (collagenous) connective tissue (possibly reticular fibers), although there is a difference of opinion as concerns this point, by observers who have given it special attention (see v. Ebner, Rose). At the surface of the pulp is a continuous layer of cells, the odontoblasts. These are columnar cells with basal nuclei and two or three processes extending into the canaliculi of the dentin, forming here the dentinal fibers already described. As a rule, the odontoblasts also send a single fiber into the pulp. These may intertwine and give rise to a network within its substance.

Peridental Membrane, Alveolar Periosteum. The tooth is joined to the alveolus by a fibrous tissue membrane, the peridental membrane or alveolar periosteum, which represents the periosteum of the alveolus and the cementum of the tooth. This consists of bundles of connective tissue (elastic fibers are here absent) directly continuous with Sharpey's fibers in the cementum and the alveolus. Between these coarser bundles of fibers, which have a direction nearly horizontal in the upper portions of the peridental membrane and incline toward the lower end of the tooth in its lower portion, there is found a looser connective tissue, containing numerous nerve-fibers, blood-vessels, and peculiar masses of epithelial cells representing the remains of the enamel organs, to be described later. These epithelial remains have by some observers been regarded as glandular in nature; further observation is, however, needed before this can be accepted as proved. At the apex of the root there is found a less dense connective tissue, continuous with that of the tooth pulp. At the neck of the tooth the peridental membrane disappears in the submucosa of the gum.

The blood-vessels of the teeth have been fully described by Lepowsky, who has studied them in a number of mammals, and in man in embryos and in full development ; his account is here followed. The artery, accompanied by the veins, enters through the apical foramen, passes up through the pulp, dividing into branches as it reaches the upper portion of the pulp cavity; these branches are spread out fan-shaped and after further division and the formation of capillaries, end in capillaries which are situated between the layer of odontoblasts and the dentin, forming here a capillary plexus which presents narrow meshes, in regions where the odontoblasts are most active.

There are in all probability no lymphatic vessels in the pulp.

Numerous medullated nerve-fibers (dendrites of sensory neurones) enter the pulp cavity through the apical foramen. Some of these lose their medullary sheaths soon after entering, or just before entering, the pulp, and divide into long, fine, varicose fibers which interlace to form a loose plexus under the odontoblasts. Other medullated fibers, grouped into small bundles, ascend in the pulp for variable distances ; the nerve-fibers of the bundles then separate and as single fibers approach the superficial portion of the pulp, and, after losing their medullary sheaths, divide into fine varicose fibers forming under the odontoblasts a plexus continuous with the plexus above mentioned. From the varicose nerve-fibers of this plexus small terminal branches are given off which terminate between the odontoblasts, or pass through the layer of odontoblasts, to end between these and the dentin (Retzius, 94 ; Huber, 98; Rygge, 1902). Medullated nerve-fibers also terminate in free endings in the peridental membrane


Development of the Teeth. In the second month of fetal life the first traces of the teeth are seen in the development of a groove along the inner edge of the fetal jaw, the dentinal or enamel groove. From the floor of the latter an epithelial ridge is formed constituting the anlage of the enamel organs and known as the dentinal ridge, or enamel ledge. At those points at which the milk-teeth later appear, the enamel ledge develops solid protuberances corresponding in number to the temporary teeth. These are known as the dentinal bulbs or enamel germs. In their first stage of development the enamel germs are knoblike, but later their bases spread, and they become flattened and finally cupshaped by the pushing up into them of connective tissue projections, the dentinal papilla. At the same time they gradually sink deeper into the underlying tissue, but still remain connected, by means of a thin cord, with the epithelium of the enamel ledge, which now lies on the inner side of the enamel germs. The enamel germs now differentiate into enamel organs. In this stage they consist of an outer layer of columnar epithelial cells, which are to be regarded as a direct continuation of the basal cells from the epithelium of the oral mucous membrane, or still better, of the enamel ledge ; the epithelium in the interior of the organ is derived from the stratum Malpighii of the oral epithelium. The cells of this layer, however, undergo a change in shape and structure, in that an increased quantity of lymph-plasma or intercellular substance collects in the interspinous spaces between the cells, pushing the cells apart, and allowing their processes to develop until the cells finally assume a stellate shape. In this way the enamel pulp is gradually formed. The next stage is characterized by a vertical growth of the dentinal papillae, which soon become surrounded on all sides by the cap-like enamel organs. The cylindric cells (enamel cells) of the enamel organs lying next to the papillae become lengthened, and after passing through further changes, finally develop into the enamel prisms of the teeth. At the periphery of the dentinal papillae, there is differentiated a layer of columnar cells, the odontoblasts, which have a connective-tissue origin, and later form the dentin. During these processes a connective -tissue mantle, the dental sac, rich in cellular and fibrous elements, is formed around each tooth anlage.

Fig. 184. Cross-section of human tooth, showing cement and dentin; X 2I2 - At a are seen small interglobular spaces (Tomes' granular layer).

The earliest appearance of the enamel is in the form of a cuticular membrane, developed from the ends of the enamel cells resting on the dentinal papilla, this cuticular membrane appearing in the form of a thin layer covering the top of the dentinal papilla. Sometime later, short striated processes Tomes' processes appear on the

Fig. 185. Nerve termination in the pulp of a rabbit's molar, stained in methyleneblue (intra vi(am) : a, Odontoblasts seen in side view ; b, a number of odontoblasts seen in end view, showing a terminal branch of a nerve-fiber situated between the odontoblasts and the dentin (Huber, "Dental Cosmos," October, 1898).

lower end of each of the enamel cells (the end toward the dentinal papilla). These are imbedded in a cement-substance, forming a continuous layer. The Tomes' processes are regarded as the beginnings of the enamel prisms. Calcification begins in the middle of these processes ; they thicken at the expense of the cementsubstance surrounding them, which later also calcifies. The enamel as a whole thickens by the elongation of the Tomes' processes of the enamel cells and by their subsequent calcification. The process ends finally in the death and partial absorption of the enamel cells and the remaining elements of the enamel organs ; these structures persist for a short time after the eruption of the tooth as a cuticular sheath.

The dentin is developed by the odontoblasts by a process analogous to that observed in the formation of bone by the osteoblasts. These epithelioid cells secrete at their outer surfaces a homogeneous substance which fuses to form a continuous layer, the membrana pr&formativa. The further development of the dentin is as follows : Its ground-substance is deposited at the cost of the lateral portions of the odontoblasts (under the membrana praeformativa), the axial portion of the cells remaining intact as the dentinal fibers ; the basal portions of the cells containing the nuclei persist, later constituting the odontoblasts of the adult pulp. By the fusion of the segments of the ground-substance formed by each cell, it becomes a homogeneous mass, but soon displays connective-tissue fibrils which gradually undergo a process of calcification. The mem brana praeformativa has no fibers and calcifies much later. It lies immediately beneath the enamel or the cementum, and in the normal tooth always contains small interglobular spaces. In the adult tooth this membrane in its entirety is known as Tomes' granular layer.

Figs. 186-189. Four stages in the development of a tooth in a sheep embryo (from the lower jaw) ; Fig. 186, Anlage of the enamel germ connected with the oral epithelium by the enamel ledge ; Fig. 187, first trace of the dentinal papilla ; Fig. 188, advanced stage with larger papilla and differentiating enamel pulp ; Fig. 189, budding from the enamel ledge of the anlage of the enamel germ, which later goes to form the enamel of a permanent tooth ; at the periphery of the papilla the odontoblasts are beginning to differentiate. Figs. iS6, 187, and 188, X IIO

Fig. 189, X 4- rt > a > a > a < Epithelium of the oral cavity ; b, b, b, l>, its basal layer ; c, t, c, the superficial cells of the enamel organ ; d, d, d, d, enamel pulp ; /, />, p, dentinal papilla ; .r, s, enamel-forming elements (enamel cells) ; <?, odontoblasts ; S, enamel germ of the permanent tooth ; v, part of the enamel ledge of a temporary tooth ; u, surrounding connective tissue.

The cementum is merely a periosteal growth of bone originating in the tissue of the dental sac and adhering to the dentin. Although at first the enamel or v vw I .

$,' a gan almost entirely sur ^ rounds the dentinal pa Fig. 190. A portion of a cross-section through a developing tooth (later stage than in Fig. 189) ; X 720 : The dentin is formed, but has become homogeneous from calcification. Bleu de Lyon differentiates it into zones (a and b). At c is seen the intimate relationship of the odontoblasts to the tissue of the dental pulp.

pilla, later a portion of that part of it in the region of the fang is absorbed in order to allow the cementum to reach the surface of the dentin.

Remains of this regressive portion persist as the epithelial nests of the dental root (compare p. 242).

The contents of the dentinal papillae change into the tissue of the dental pulp.

As early as the third month outgrowths appear on the inner side of the enamel ledge next to the partly developed milk-teeth, which represent the anlagen of the enamel organs of the permanent teeth. Their further development is similar to that of the milk teeth. The enamel organs of the molars are also developed from an enamel ledge which is practically a backward continuation of the embryonic enamel ledge. With their crowns presenting, the temporary teeth at last break through the epithelium of the gums. When the development of the permanent teeth is so far advanced that they are ready to perforate, regressive processes begin at the roots of the milk-teeth, which are due, as in like conditions of the bone, to the action of certain cells, which are here known as " odontoclasts." The crowns of the milk-teeth are then thrown off, one by one, by the growing permanent teeth.

For further information as to the teeth and their development, see the articles by v. Ebner (Scheff 's " Handbuch der Zahnheilkunde" and in Kolliker's "Handbuch der Gewebelehre," Bd. iii), whose studies we have to a great extent followed on this subject.

2. The Tongue

The Lingual Mucous Membrane and its Papillae.

The mucous membrane of the tongue differs in general very little from that lining the rest of the oral cavity. It must, however, be borne in mind that in the greater part of the tongue the submucosa is poorly developed, and as a consequence the mucous membrane on the upper surface and base of the tongue is scarcely movable. Other peculiarities of the lingual mucous membrane are the absence of glands in the mucosa on the upper surface of the tongue, although glands are found in the musculature of the tongue, their ducts passing through the mucosa, the presence of epithelial papillae, and of lymph-follicles at the base of the tongue.

Fig. 191. Fungiform papilla from human tongue.

The upper surface of the tongue is roughened by the presence of epithelial projections, the lingual papilla. The latter are almost entirely epithelial structures, and should not be confused with those papillae which are composed exclusively of connective tissue. There are several classes of lingual papillae the filiform, the fungiform, and the circumvallate papillae. The most numerous are the threadlike or filiform papillcz (from 0.7 to 3 mm. long). These are scattered over the entire upper surface of the tongue, and consist of conic projections of the epithelium and of the mucosa. The connective-tissue portions of these papillae are very thin and long. The basal layers of the epithelium can not be distinguished from the same layers covering the surrounding mucosa, but the more super

Fig. 192. From a cross-section of the human tongue, showing short, thread-like papillae

(filiform) ; X I 4 ficial layers are differentiated, in that their cells are arranged parallel to the long axes of the papillae and overlap each other like tiles (Fig. 192). Their free ends are often continued into several spinelike processes. Less numerous than the filiform are the fungiform papillcs (from 0.7 to 1.8 mm. in height) scattered here and there between the former. They are nearly hemispheric in shape, and are joined to the surface of the tongue by a slightly constricted base. At times they are even partly sunk into the mucous membrane. The mucosa is raised under the epithelium to form connective-tissue papillae (Fig. 191). On the free surface of the fungiform papillae are sometimes found taste-buds, or taste-goblets, which lie imbedded in the epithelium and extend through its entire thickness. The circumvallate papilla occupy a definite region on the upper surface of the tongue, and are arranged in two rows, forming almost a right angle, with the apex directed backward and situated just in front of the foramen caecum (Morgagni). These papillae are few in number, about eight to fifteen in all. In shape they are similar to those of the fungiform type, but are much larger (about I or 2 mm. in diameter), and sunk so deeply into the mucous membrane that the latter forms a wall around their sides. Here also the mucosa passes up into the papillae and forms connective-tissue papillse of its own at the upper surface, while at the sides it merely adheres to the smooth inner surface of the epithelial layer. Taste-buds are found in the epithelium at the sides of the papillae, and also in that of the ridges surrounding the papillae. At the sides of the human tongue and near its base are the so-called fimbrice lingua. These are irregular folds of mucous membrane,

Fig. 193. Longitudinal section of foliate papilla of rabbit, showing taste-buds.

the sides of which also contain taste-buds. In the rabbit they are more regular in structure and consist of parallel folds of mucous membrane thickly dotted with taste-buds, and are termed the foliate papilla. In place of the circumvallate papillae, the guinea-pig possesses structures similar to the foliate papillae of the rabbit.

Into the depressions in which the circumvallate papillae lie and into those between the folds of the fimbriae linguae open the ducts of numerous serous glands, the glands of v. Ebner (see below).

The Taste-buds. The gustatory organs in the form of tastebuds are found on the surface of the tongue, principally on the lateral surfaces of the circumvallate papillae and the fimbriae linguae (foliate papillae). They are also occasionally met with in the epithelium of the fungiform papillae and the soft palate, and on the posterior surface of the epiglottis. They always lie imbedded in the epithelium and extend through its entire thickness ; they are ovoid in form, with base downward and the smaller pole at the surface. The whole structure is surrounded by the epithelium of the mucous membrane of the regions in which they occur, except at the attenuated outer end of the taste-bud, where, by means of a small opening, the taste-pore, it communicates with the oral cavity. Most of the cells constituting the taste-buds are elongated, spindle-shaped structures, extending from one end of the organ to the other, with spaces between them. There are four varieties of these cells : (i) The outer sustentacular or tegmental cells, lying at the periphery of the organ with a nucleus in their center, and having a short, cone-shaped cuticular projection ; (2) the inner sustentacular or rod-shaped cells, which are more slender structures with basally situated nuclei and without a cuticular projection ; between the latter are (3) elongated, spindle-shaped, neuro-epithe

Fig. 194. Longitudinal section of a human circumvallate papilla; X 2O lial cells, with the nucleus of each in the thickest portion of the cell, and with slender, stiff processes projecting into the taste-pore ; (4) a few broad basal cells, communicating with each other as well as with the sustentacular cells by numerous processes. We have, therefore, in the cells of the first, second, and probably fourth varieties, elements which belong exclusively to the sustentacular apparatus of the organ (Hermann, 85, 88).

Von Ebner found in the taste-buds of the circumvallate papillae of man, monkey, and cat, as well as of the papillae foliatae of the rabbit, an open space situated between the taste-pore and the tip of the taste-bud (Fig. 195). These spaces vary according to the species, and are bounded above by the summits of the tegmental cells and laterally and below by the more centrally situated sustentacular cells. The cavities are often 10 ft in depth, and are filled with a fluid apparently in communication with the fluid of the depression into which the circumvallate papillae are sunk. The processes of the neuro-epithelial cells project into the cavity from its floor and lateral walls, but do not extend as far as the tastepore.

The circumvallate papillae are differentiated from the adjacent surface of the tongue by the development of a solid encircling epithelial ridge. Numerous taste-buds appear on the surface quite early in the history of the embryo. These, however, disappear completely when the permanent taste - buds develop from the basal cells of the epithelial ridge. Similar phenomena occur in the fungiform papillae (Hermann,

Fig. 195. Schematic representation of a taste-goblet (partly after Hermann, 88).

The neural epithelia of the taste-goblets were formerly regarded as directly connected with the nerve-fibers by means of long processes, but the latest researches have shown that dendrites of sensory neurones (sensory nerves) enter the taste-buds and end free in telodendria. The latter surround the neuro-epithelial and, to some extent, the sustentacular cells, their relations depending upon contact.

The Lymph-follicles of the Tongue (Folliculi linguales) and the Tonsils. At the root of the tongue, and especially at its sides, are numerous elevations due to the increased quantity of lymphoid tissue found in the mucosa of these regions, the lingual tonsils, or lingual follicles. In the center of each follicle is a cavity communicating with the exterior and caused by an invagination of the epithelium. The lymphoid tissue contains a number of more or less distinctly defined lymph-nodules, some even showing germ centers (vid. p. 197). The whole structure is surrounded by a connective-tissue capsule. The epithelial walls of the follicular cavities often show extensive degenerative changes, which are accompanied by increased migration of leucocytes into the oral cavity. These leucocytes change (according to Stohr, 84) into the so-called mucous or salivary corpuscles of the saliva.

Pharyngeal Tonsil.

The pharyngeal tonsils may be regarded as clusters of small lymph -follicles, similar to those found in the tongue. The pharyngeal tonsil presents numerous irregularly formed crypts, lined by stratified pavement epithelium. These crypts are often widened at the base and are provided with irregular saccular enlargements. The crypts are all surrounded with lymphoid tissue, which may be regarded as diffuse lymphoid tissue in which are found numerous lymphoid follicles, often showing germ-centers. The lymphoid tissue is bounded externally by fibrous tissue, septa of which pass into the lymphoid tissue surrounding the crypts.

Fig. 196. Section through the pharyngeal tonsil of man; X 6^ : agp, Arcus glosso-palatinus ; ep, epithelium;/?, crypt; M, striated muscle; nl, lymphoid nodules; S, connective tissue septa ; sf, remains of tonsillar sinus.

The epithelium lining the crypts or cavities of the tonsils shows, as in the lingual follicles, extensive degenerative changes, resulting mainly in the formation of variously shaped communicating spaces filled with lymphocytes and leucocytes. (See Fig. 197.)

Besides the nerves terminating in the taste-buds, the tongue is richly supplied with sensory nerves which terminate in free sensory endings, which may be traced into the epithelium, and which are especially numerous in the fungiform and circumvallate papillae ; or in smaller or larger end-bulbs of Krause found in the mucosa of the fungiform papillae. The motor nerves of the tongue terminate in motor endings.


The glands of the oral cavity comprise numerous branched tubulo-alveolar glands situated in the mucosa and submucosa of the lips, cheek, and tongue; branched tubular glands in the region of the circumvallate papillae; of a pair of compound branched alveolar glands, the parotid ; and of two pairs of compound branched tubulo-alveolar glands, the submaxillary and sublingual. These are classified according to their secretions into those secreting principally mucus (human sublingual and many of the smaller oral glands), and known as mucous glands ; those secreting a fluid albuminoid substance containing no mucus, the serous glands (parotid glands and the small glands near the circumvallate papillae) ; and those having a mixed secretion, mucous and serous glands (human submaxillary). The ducts of all these glands open into the cavity of the mouth. The ducts of the smaller oral glands are, as a rule, short and pass up through the mucosa and the epithelium to open on the free surface. The principal excretory ducts of the large salivary glands are Steno's ducts (Stenson's ducts), passing from the parotid glands to the mouth ; Wharton's ducts, the ducts of the submaxillary glands, and Bartholin's ducts for the sublingual glands. The salivary glands consist of numerous lobules and small lobes of glandular tissue, surrounded by a thin fibroustissue capsule which sends septa and trabeculae between the lobules and lobes. The duct of each gland on reaching the gland divides into smaller ducts, which penetrate the gland between the lobes and lobules, dividing and redividing in their course; the terminal branches enter the lobules and join the tubules and alveoli. The ducts of the human submaxillary glands have been carefully investigated by Flint ; his account is here followed. The submaxillary duct (Wharton's duct) generally divides into three primary ducts, which extend in various directions and are usually relatively short, dividing into the interlobular ducts, which often run for relatively long distances before giving off individual branches. They run in the connective tissue between the lobules, and give off branches and end in ducts which ramify between the lobules and are known as sublobular ducts, which in turn give rise to lobar ducts, which generally ramify through three or four divisions which follow in close succession, forming the intralobular ducts. These radiate from the centre toward the periphery of the lobules, without, however, reaching the periphery. The terminal branches of the intralobular ducts are the intermediate ducts (intercalary), which are in communication with the secretory compartment, the tubules.

Fig. 197. The area designated by a in the previous illustration, shown by a higher magnification; \' about 150: a, Leucocytes in the epithelium; b, one of the spaces in the epithelium filled with leucocytes and more or less changed epithelial cells ; c, blood-vessel ; d, normal epithelium ; e, basal cell of the same.

The epithelium lining the different portions of the large excretory ducts varies somewhat. For a short distance from their oral end they are lined by a stratified columnar epithelium consisting of two layers of cells (Wharton's ducts are now and then lined for a short distance by a stratified pavement epithelium continuous with that lining the mouth). Beyond this stratified columnar epithelium, which extends for a variable distance along the large excretory ducts, the interlobular ducts and the sublobular ducts are lined by a pseudostratified columnar epithelium, possessing two rows of nuclei (Steiner). The intralobular ducts are lined by a single layer of columnar cells, the basal half of each cell showing a distinct striation. The intermediate portions of the ducts are lined by a low, cubic, or flattened epithelium. The epithelium of the ducts rests on a basement membrane, consisting of very fine, closely woven connective-tissue fibrils (Flint). External to this there is a sheath of areolar connective tissue, which shows external to the basement membrane a layer of closely woven elastic fibers. The larger divisions of the duct have nonstriated muscle-cells in their walls.

Between the membrana propria and the secreting epithelium of the tube, and more especially in the acini, are branched cells which anastomose with each other, the so-called basket cells. The origin of these cells has not been fully determined ; their existence even has been questioned. Their processes penetrate between the glandular cells and form a supporting structure for them. The membrana propria surrounding the entire glandular tube is in close relationship to these cells.

We shall now consider more in detail the structure of the alveoli, tubules, and of the salivary glands.


The Parotid Gland (Serous Gland). The parotid glands may be classed as compound branched alveolar glands. The gland is made up of distinct lobes and lobules. The secreting compartments consist of irregular, convoluted tubules, which are joined by a narrow intermediate duct to the intralobular ducts. The epithelial cells lining the acini of this gland are short, irregularly columnar or cubic cells, with round or oval nuclei, situated nearer the basal portions of the cells, the protoplasm presenting different

Fig. 198. Section through salivary gland of rabbit, with injected blood-vessels ; X 7

appearances according to their physiologic condition. When at rest, the cells are filled with fine granules, which are to be regarded as consisting of a substance from which the specific secretion is formed, a substance known as zymogen, the granules being known as zymogen granules. These granules are in the paraplasm of the cells, from which they are probably developed. As secretion proceeds the outer portion of the cell becomes free from granules, these being used up in the formation of the secretion (Langley).

The Sublingual Gland (Mucous Gland). The sublingual glands are compound branched tubulo-alveolar glands. These glands may be regarded as made up of numerous smaller glands. The ducts divide and redivide, as above described, with this exception, that the secreting compartments are not joined to the intralobular ducts, with striated epithelium, by means of narrow intermediate ducts, as these divisions of the duct system are lacking in these glands (Maziarski). The general arrangement of the secreting compartments in a small portion of a sublingual gland is shown in Fig. 199. The size of the tubules and alveolar enlargements varies. In the tubules and alveoli there are two varieties of cells: cells which form mucus and cells which have a serous secretion. The cells which form mucus, appear clear in preparations treated after the ordinary methods' used in the laboratories. In fresh

Fig. 199. Model of a small portion of a sublingual gland of man ; X 1 4- The demilunes of Heidenhain are more deeply shaded (Maziarski, " Anatomische Hefte," 1901).

preparations teased in serum or in 2 ^ to 5 % sodium chlorid solution (Langley), or when fixed and stained after special methods, it may be seen that the secretion is first formed in the form of large granules, consisting of a substance known as mucigen, which breaks down to form the mucus, much as described for mucous or goblet cells (see page 87). In preparations the cells of which are stored with mucigen the nuclei are situated at the periphery of the tubules and alveoli, near the basement membranes. The cells with serous secretion are situated in close apposition to the basement membrane; they resemble in structure serous cells, and are found either singly or in groups of crescentic shape. These groups are known as the crescents of Gianuzzi or the demilunes of Heidenhain. The margins of the individual cells composing the crescents are often so faintly outlined that the whole structure has the appearance of a large poly nuclear giant cell.

The demilunar cells have been variously interpreted by different observers. They have been regarded as permanent cells with a special secretion, as transitional structures, and again as cells destined to replace the degenerated mucous cells. Stohr (87) believes that the cells of the acini are never destroyed in the process of mucous secretion, and that the crescents of Gianuzzi are therefore merely a complex of cells containing no secretion, which have been crowded to the wall by the adjacent enlarged and distended cells. Solger (96), on the other hand, does not regard the demilunes as transitional structures whose function is to replace the destroyed cells, but considers them to be permanent secreting cells an opinion which he bases on Jthe results of special methods of

Fig. 200. From section of human submaxillary gland.

Connective tissue.

Fig. 2O1. Section from parotid gland of man.

investigation. According to him, then, the mucous salivary glands are mixed glands, in that the demilunes consist of cells of a serous type, while the remaining elements are mucous in character. The destruction of mucous cells during secretion is not admitted by him (compare also R. Krause). This latter view seems more in accord v/ith recent observations.

The Submaxillary Gland (Mixed Gland). The submaxillary gland of man is a gland composed of tubules similar in shape and structure to those found in the parotid gland, having a serous secretion, and of tubules with alveolar enlargements, lined with cells

Fig. 202. Portion of a model of a salivary gland with mucous secretion : a, intralobular duct ; b, intermediate duct ; c, tubules and alveoli lined by mucous cells ; d, demilunes of Heidenhain (from Bohm and Davidoff, third German edition).

which form mucus. These mucus-secreting tubules are joined to intermediary ducts which are branches of intralobular ducts with striated epithelium. The mucus-forming tubules show the demilunes of Heidenhain. The submaxillary glands of man are there

Fig. 203. A number of alveoli from the submaxillary gland of dog, stained in chrome^ silver, showing some of the fine intercellular tubules.

fore mixed glands, with both serous and mucous secretion, the respective tubules or groups of tubules showing the characteristics of mucous and serous glands. In Fig. 202 is shown a portion of a model of a salivary gland, with mucous secretion.

By means of various -methods the existence of a network of tubules surrounding the glandular cells may be demonstrated both in the serous and mucous glands. The same arrangement may be observed in the case of the cells forming the demilunes. The course of these tubules may be followed to their junction with the lumen of the secreting portion of the gland tubule, and the whole structure would seem to indicate that the entire surface of the cells is concerned in the act of secretion (Erik Muller, 05 ; Stohr 96, II).

As to the part that the intermediate tubules and the intralobular tubes play in the process of secretion, Merkel's (83) theory is of interest. He believes that the former yield a part of the water in the saliva, while the salts are furnished by the rod-shaped epithelium of the intralobular tubes. These views of Merkel have been questioned, as it has been shown by chemic analysis that the relative quantity of water and salts in the secretion of the salivary glands is not at all proportionate to the number of the intermediate tubules and intralobular tubes. For example, Werther finds that although a great many intermediate tubules are present in the parotid gland of the rabbit and none at all in the submaxillary gland of the dog, nevertheless the secretions of these glands contain equal quantities of water. Furthermore, the secretions of the parotid of the rabbit and of the sublingual of the dog show equal quantities of salts, in spite of the fact that in the former there are large numbers of intralobular tubes with rod-shaped epithelium and in the latter none at all.


Besides the larger glands, there are in the oral cavity numerous small lobular, tubulo-alveolar and simple branched tubulo-alveolar glands. They are mostly glands with mucous secretion. In many of them demilunes of Heidenhain may be made out, most clearly in those of the lips (J. Nadler). They are known, according to their location, as glandulae labiales, palatinae, and linguales. The absence of intralobular tubes and well-defined intermediate tubules is characteristic of all the smaller glands of the oral cavity. As a consequence the secreting tubules are composed almost entirely of those parts corresponding to the acini of the larger glands. Branched tubular glands, with serous secretion, known as v. Ebner's glands, occur in the tongue, their ducts opening into the depressions of the circumvallate and foliate papillae, while the secreting tubules extend into the muscular portion of the tongue. The general character of v. Ebner's glands is shown in Fig. 204.

The salivary glands and smaller glands of the mouth have a rich blood supply. In the salivary glands the arteries follow the ducts through their repeated branching, ultimately ending in capillaries which form a network inclosing the acini and the terminal portions of the system of ducts. The blood-vessels for each lobule are quite distinct, forming only few anastomoses with those of neighboring lobules.

The Lymphatics. In the connective tissue surrounding and separating the acini there are found clefts, which contain lymph. These clefts are in part between the blood-capillaries and the basement membranes. Lymph-vessels are found in the connective tissue separating the lobules and lobes of the gland, in which they follow the duct system. Lymph-vessels have not been found in the lobules.

Fig. 204. Model of a gland of v. Ebner. from a boy fourteen years old ; X I 7(Maziarski, " Anatomische Hefte," 1901.)

The nerve supply of the salivary glands, may, owing to the importance of these structures, receive somewhat fuller consideration. Their nerve supply is from several sources. That of the sublingual and submaxillary glands will be considered first. Sensory nerve-fibers (no doubt the dendrites of sensory neurones, the cellbodies of which are situated in the geniculate ganglion) terminate in free sensory endings in the large excretory ducts and their branches. These medullated fibers accompany the ducts in the form of small bundles. From place to place one or several fibers leave these bundles and, after dividing a number of times, lose their medullary sheaths. After further division the nonmedullated branches form plexuses under the epithelial lining of the ducts. From the fibers of these plexuses terminal fibrils are given off, which enter the epithelium, to end, often near the free surface, on the epithelial cells (Arnstein, 95; Huber, 96). The secretory cells of the acini receive their innervation from sympathetic neurones. The cell-bodies of those supplying the sublingual glands are grouped in a number of small, sympathetic ganglia situated in a small triangle formed by the lingual nerve, the chorda tympani and Wharton's duct, the chordalingual triangle. These ganglia may be known as the sublingual ganglia (Langley). The cell-bodies of the sympathetic neurones supplying the secretory cells of the submaxillary glands are grouped in small ganglia situated on Wharton's duct just before it enters the gland, in the hilum of the gland, and on the interlobar and interlobular ducts ; they may be spoken of collectively as the submaxillary ganglia. In the glands under discussion, the neuraxes of the sympathetic neurones are grouped to form small bundles, which divide repeatedly, the resulting divisions joining to form plexuses situated in the outer portion of the walls of the ducts, and as such may be followed along the ducts, the bundles of nerve-fibers becoming smaller and the division of the bundles of fibers and the individual fibers occurring oftener as the smaller divisions of the system of ducts are reached. On reaching the acini, the terminal branches of the nerve-fibers form a plexus outside of the basement membrane, epilainellar plexiis ; from this branches are given off which penetrate the basement membrane, some forming zhypolamellar plexus, others ending on the gland-cells in small granules or clusters of granules (Arnstein). Throughout their entire course the neuraxes of the sympathetic neurones are varicose, nonmedullated nerve-fibers. The nerve-fibers of the chorda tympani end in terminal end-baskets, inclosing the cell-bodies of the sympathetic neurones found in the sublingual and submaxillary ganglia, and not in the glands, as generally stated by writers. The increase of secretion from the submaxillary and sublingual glands on direct or indirect stimulation of the chorda tympani is due, therefore, not to a direct stimulation of the gland-cells by the fibers of this nerve, but to a stimulation of the sympathetic neurones of the sublingual and submaxillary ganglia, the neuraxes of which convey the impulse to the gland-cells. These glands have a further nerve supply from the superior cervical ganglia of the cervical sympathetic. The neuraxes of sympathetic neurones, the cell-bodies of which are situated in the superior cervical ganglia, accompany the blood-vessels to the sublingual and submaxillary glands ; their mode of termination is, however, not as yet determined. The cell-bodies of the sympathetic neurones here in question are surrounded by end-baskets of nerves which leave the spinal cord through the second, third, and fourth dorsal spinal roots. The blood-vessels of the salivary glands are also richly supplied with vasomotor nerves, the neuraxes of sympathetic neurones, which terminate on the muscle-cells of their walls. The nerve supply of the parotid glands is, in the main, like that of the other salivary glands here described, although it has not been worked out with the same detail. The cell-bodies of the sympathetic neurones, the neuraxes of which innervate the gland-cells, are, it would appear, situated in the otic ganglia. The nerve-ending in the smaller glands of the mouth is similar to that given for the salivary glands, as has been shown by Retzius and other observers. It is very probable that the cell-bodies of the sympathetic neurones, the neuraxes of which innervate the glands of the tongue, are situated in the small sympathetic ganglia found on the lingual branches of the glossopharyngeal and lingual nerves.

B. The Pharynx and Esophagus


The epithelium of the pharynx is of the stratified squamous variety, and also contains prickle cells and keratohyalin. (See Skin.) A stratified ciliated epithelium is present only in the fornix in the region of the posterior nares. The area covered by this type of epithelium is more extensive in the fetus and new-born, and extends over the whole nasopharyngcal vault. In the human embryo the superficial epithelial cells of the esophagus possess cilia up to the thirty-second week (Neumann, 76). The papillae of the mucosa are loosely arranged and are in the form of slender cones. The mucosa of the pharynx contains diffuse adenoid tissue rich in cells \vhich in some places forms accessory tonsils (vid. p. 251); it is bounded externally by a well -developed layer of elastic fibers which occupies the same relative position as does the muscularis mucosae in the esophagus. External to this elastic layer, there is found a muscular coat consisting of striated muscle-fibers.

Esophagus. The esophagus is lined by a stratified pavement epithelium, which rests on a papillated mucosa, consisting of fibrous tissue which contains few elastic fibers and is bounded externally by a muscularis mucosae, the majority of the cells of which show a longitudinal arrangement. External to the muscularis mucosae there is found a well-developed submucosa, consisting of loosely woven fibre-elastic connective tissue. Outside of the submucosa there is found a muscular layer, consisting of an inner circular and an outer longitudinal layer. These muscular layers consist in the upper half of the esophagus mainly of striated muscle-fibers, while in the lower half they consist almost wholly of nonstriated muscular tissue. There is, however, no sharply defined line of demarcation between the two types of muscular tissue, as the fibers of the unstriped variety penetrate for some distance upward into the substance of the striated muscle, giving the tissue here a mixed character.

The esophagus contains two varieties of glands: (i) Mucous glands of the type of branched tubulo-alveolar glands. The secreting portions of these glands are situated in the submucosa, while the ducts pass through the muscularis mucosae to the surface. The secreting tubules and alveoli are lined by mucous cells ; demilunes are absent. The ducts, which often show cystic dilations, are lined for the greater part by a single layer of columnar cells ; at their termination they often possess a lining of stratified pavement epithelium. (2) The other variety of glands are found in two zones, the one situated at the upper end of the esophagus, in a region opposite the cricoid cartilage to the fifth tracheal cartilage (superficial glands of esophagus, Hewlett; upper cardiac gland, Schaffer), the other at the end of the esophagus, just before it enters the stomach the esophageal cardiac glands. These glands are situated above the muscularis mucosae, and are of the branched

Fig. 205. Section of esophagus of dog; X 1 & tubular variety. The ducts of these glands, which reach the surface through the apices of the connective tissue papillae, are lined by a single layer of columnar epithelial cells. The secreting portions of the tubules are lined by shorter columnar cells. Here and there cells like the parietal cells of the fundus glands of the stomach, to be described later, are also found, as also cells showing a mucous secretion. The cardiac glands of the esophagus are similar to the glands of the same name found at the cardiac end of the stomach, with which they may be said to be continuous, and which will receive further consideration.

C. The Stomach And Intestine

1. General Structure of the Intestinal Mucous Membrane

The mucous membrane of the stomach and intestine, unlike that of the esophagus and oral cavity, possesses an epithelium of the simple columnar variety with elongated cells (about 22 p in

Fig. 206. Part of section of human esophagus, showing a cardiac gland with a

dilated duct; X I2 height). At the cardia the stratified squamous epithelium of the esophagus terminates abruptly, the basilar layer of the esophageal epithelium being continued as the simple columnar epithelium of the stomach. In the intestine the epithelium shows a well-marked striated cuticular border, striated protoplasm in the outer ends of the cells, extending to the immediate vicinity of the nuclei, which are situated in the basal portions of the cells. The basal portion of each cell consists of nonstriated protoplasm, ending in a longer or shorter process which extends to the basement membrane, or possibly even penetrates it. The epithelial cells have the power of producing mucus, a phenomenon which, in the normal condition, rarely embraces whole areas of epithelium ; these cells (goblet cells) are usually surrounded by others which are unchanged (for details about goblet cells see General Histology, p. 87). Throughout the entire intestinal tract the epithelium forms simple, branched, and compound tubular and alveolar glands. These are depressions lying in the mucosa, and only in the duodenum extend beyond it into the submucosa.

The mucosa consists of adenoid tissue, consisting of reticular fibers and a fine network of elastic fibers, containing relatively few cells. It fills the interstices between the glands, and often forms a thin but continuous layer (granular layer of F. P. Mall) below the glands. It is therefore obvious that the development of the mucosa is inversely proportionate to the number and the density of arrangement of the glands ; when the latter are present in large numbers, as, for instance, in the stomach, the mucosa is reduced to a minimum. In the small intestine it forms not only the permanent folds, but also certain leaf-like and finger-like elevations known as villi, which are covered with epithelium and project into the lumen of the intestine, thus increasing to a considerable extent the surface area of the mucous membrane. In the mucosa are found small nodules of adenoid tissue. These are spoken of as lenticular glands when occurring in the stomach, as solitary glands when found in the upper portion of the small intestine and in the large intestine. In the lower portion of the small intestine they are grouped to form the agminated glands, or Peyer's patches, which, when large, extend into the submucosa. In the external portion of the mucosa there is found a thin, somewhat denser layer, known as the stratum fibrosum (F. P. Mall), consisting mainly of white fibrous tissue (Spalteholz) ; and external to this is a layer consisting of two or three strata of unstriped muscle-fibers, the muscularis mncostz. As a rule, it is composed of an inner circular and an outer longitudinal layer. This arrangement is interrupted only where the larger glands and follicles penetrate into the submucosa. The epithelium with the glands, the mucosa with its lymph-nodules, and the muscularis mucosae form together the mucous membrane, or tunica mucosa.

Below the mucous membrane is the connective-tissue submucosa. This is characterized by its loose structure, and consequently affords considerable mobility to the mucous membrane. In the small intestine it forms a large number of permanent transverse folds known as valvnlce conniventcs (Kerkring). In the submucosa of the duodenum occur the secreting portions of Brunner's glands (glandular duodenales), and in the small intestine the larger lymph-nodes and Peyer's patches.

External to the submucosa is the muscular coat, which generally consists of two layers of unstriped muscle-tissue. The inner layer is composed of circular fibers (stratum circulare) ; the outer layer, of longitudinal fibers (stratum longitudinale). In the colon the longitudinal layer forms definite bands, the tcenice coli. In some regions the circular fibers are also considerably reinforced, particularly in the plica sigmoidea: which lie between the taeniae coli. At these points the longitudinal layer also is thickened. In the rectum the circular fibers form the internal sphincter ani muscle. In the stomach a third layer is added to the two already mentioned, with fibers running obliquely. It lies internal to the circular fibers, but does not form a continuous layer.

According to Legge, elastic fibers are present throughout the entire digestive tract of all adult mammalia and vary only in minor details in the different species. In regions in which the tunica muscularis is prominent the elastic fibers attain a considerable size. There is also a difference in their development in carnivora and herbivora. In general, they form a dense network, present not only in the serous layer, but also in the submucosa and mucosa. These fibers preserve the elasticity of the intestinal walls and resist any hyperextension of the glands and follicles.

The intestine is covered externally by the peritoneum, forming the serous coat, which consists of an inner, very thin connective tissue layer (subserosa) and an outer layer of mesothelial cells.

2. The Stomach

The general structure of the gastric mucous membrane is essen tially the same as that of the intestinal canal. It consists of a relatively coarse adenoid reticulum, the spaces of which contain lymphocytes and leucocytes, and E itheiiai plasma cells. Thin strands or ceil, bundles of nonstriated muscle cells may be traced from the muscularis mucosae to various levels in the mucosa. It presents depressions or infoldings known as crypts (foveolae, stomach-pits, gland ducts) into which the glands open. In the fundus the crypts attain a depth of from one-fifth to one-sixth the thickFig. 207. Epithelium of human stom- , ach, covering the fold of mucosa between ness of the mucous membrane, two gastric crypts ; x 7- In the pylorus they are deeper, many of them here extending through half the mucous membrane and some even reaching to near the muscularis mucosae. The epithelium of the crypts and that of the folds between them is composed of long, slender cells, with basally situated nuclei. That portion of the cell-body near its free margin contains very little protoplasm, but presents a welldeveloped mucous plug or theca, occupying the outer one-fourth or one-third of the cell ; the region of the cell containing the nucleus possesses more protoplasm. This part of the cell extends downward in a curved process of diminishing size, which assumes a position parallel to the corresponding parts of the neighboring cells, and nearly parallel to the basement membrane.

Three varieties of glands occur in the stomach : (i) Cardiac glands; (2) fundus glands ; (3) pyloric glands.

Bodies of gastric glands.

Fig. 208. From vertical section through fundus of human stomach ; X 60 : a and b, Interlacing fibers of the muscularis mucosse ; from a and b muscular fibers enter the mucosa. The fibers of the layer b penetrate those of layer a.

Fig. 209. A number of fundus glands from the fundus of the stomach of young dog, stained after the chrome-silver method, showing the system of fine canals surrounding the parietal cells and communicating with the lumen of the glands.

I. The cardiac glands have recently been subjected to careful investigation by Bensley; his account is here followed. They occur in the region of the junction of the esophagus and stomach, occupying a zone varying somewhat in width, but may be as wide as 4.3 cm. The glands are of the type of branched tubulo-alveolar glands. The tubules and alveoli are not of uniform structure. The majority of the lining cells are mucus secreting cells, and may be recognized as such in suitably stained preparations, cells with zymogen granules, similar to the chief cells of the body of the fundus glands (see these), are also found, as also the parietal cells, as found in the latter glands. The cardiac glands may be regarded as decadent structures.

2. The fundus glands (peptic glands) consist of a crypt or foveola, into which empty three to five, or even more, unbranched and branched tubules, which often show irregular terminal enlargements. The tubules vary in length, measuring from 0.4 to 2.2 mm. The upper end of a fundus tubule is slightly narrower and presents structural peculiarities, and is known as the neck of the gland. The main portion of the gland is called its body, and the region at its distal blind end the fundus.

Fig. 210. From a section through the junction of the human esophagus and cardia ; X5

The fundus glands, as their name suggests, are found in the fundus or cardiac end of the stomach, and are lined by two kinds of cells : parietal (border cells, acid, oxyntic, or delomorphous cells R. Heidenhain, 69; Rollet, 70) and chief, central, peptic, or adelomorphous cells. The parietal cells lie against the walls of the gland that is, they rest on its basement membrane and are particularly numerous in the neck and body of the gland, but not so numerous in its fundus. Their bodies often extend more or less beyond the even line of the remaining cells, thus forming, together with the membrana propria, a protuberance (particularly noticeable in the pig, where almost the entire cell may be enveloped by the basement membrane, giving it an appearance of being entirely extraglandular). Toward the lumen of the gland the contour of these cells is modified by pressure on the part of the adjacent cells belonging to the other variety, and they are indented according to the number of the latter. Occasionally, a process is seen extending from a parietal cell to the lumen of the gland. The parietal cells are larger than the cells of the other variety and richer in protoplasm ; they are of an irregular oval or triangular shape and possess, as a rule, a single nucleus, although in man numerous parietal cells with two nuclei are found. The parietal cells are clearer in fresh preparations than are the chief cells, while in fixed preparations the reverse is generally the case. They stain deeply in Heidenhain's iron-lac-hematoxylin, are darkened by osmic acid, and show an affinity for acid stains, especially for eosin, also for congo-red and for neutral carmine solutions.

According to Erik Miiller and Golgi (93), there exists in the peripheral protoplasm of each parietal cell a system of canals in the form of a network communicating with the lumen of the gland and varying in structure according to the physiologic condition of the cell wide-meshed in a state of hunger and fine-meshed during digestion. A peripheral zone differing from the rest of the cellbody may occasionally be demonstrated in the parietal cells (mouse) by using the method of von Altmann.

The chief cells are short, irregular, columnar structures whose narrower portions point toward the lumen of the gland. They are situated either directly between the lumen and the basement membrane of the gland, or their basilar surfaces border on a delomorphous cell. They are found throughout the tubule of the gland and occupy the spaces between the delomorphous cells. The chief cells of the fund us glands are of two varieties, as has been shown by Bensley. The chief cells of the body of the gland are characterized by the possession of relatively large zymogen granules, which are found in the inner portion of the cells. These granules are used up during secretion. The outer or basal portion of the cells contains a prozymogen, not in granular form but recognized by its staining reaction. The chief cells of the neck are slightly smaller than those of the body, and differ from these in that they do not possess zymogen granules and prozymogen only in small amounts, but show by their reaction to certain stains that they are mucus-secreting cells.

The structure of the pyloric region of the stomach differs in some respects from that of the cardiac end and fundus. There is, however, no sharply defined boundary between fundus and pylorus, but a transitional zone in which changes gradually take place. Toward the pylorus the gastric crypts gradually become deeper and the parietal cells decrease in number. Here also the glands branch more freely. In the pylorus itself the crypts frequently extend half-way through the thickness of the mucous membrane, often even penetrating nearly to the muscularis mucosae, in which case the corresponding tubules become tortuous and arch over the muscularis mucosae. The glands of the pyloric region are therefore to be classified as branched tubular glands (De Witt).

Fig. 211. From vertical section through human pylorus ; X about 60.

Among the branched pyloric glands are found glands which show no distinct branching. The most important feature is that in the great majority of the tubules only a single variety of cell is present in the pyloric gland. (Only here and there are found parietal cells in the pyloric glands of the human stomach.) These cells may be compared with the chief cells of the neck regions of the fundus glands, in that they show no zymogen granules, and prozymogen only in small quantity, and on staining with special stains, it can be shown that their secretion is mucus. They are of columnar shape, and more uniformly so than the chief cells of the fundus glands a condition probably due to the general absence of delomorphous cells. In the immediate vicinity of the gastroduodenal valve the pyloric glands become shorter, and other glands, which extend into the submucosa, and which are identical in structure with the glands of Brunner in the duodenum, make their appearance. In this portion of the pylorus are also a few scattered villi, which from their structure may be considered as belonging to the duodenum (vid. Fig. 218).

In the normal condition the mucosa of the stomach contains solitary lymph-nodules (lenticular glands) in the fundus region; they are, however, more frequent in the pyloric region ; well-defined lymph-nodules are constantly present in the immediate vicinity of the pylorus.

The muscularis mucosae is usually composed of three layers, the fibers of the individual layers forming distinct interlacing bundles. Individual muscle-fibers very frequently branch off from the inner layer, assume a vertical position and disappear among the glands. This arrangement is especially well seen in the muscularis mucosae of the fundus of the stomach (Fig. 208).

Only the inner and middle layers of the muscular coat of the stomach enter into the formation of the sphincter pylori (Fig. 2 1 8). The fibers of the outer layer, however, penetrate through the sphincter pylori and may even be traced into the submucosa. When these alone contract, the muscular bundles of the sphincter act somewhat as pulleys, and a moderate dilatation of the lumen of the pylorus is the result ( dilatator pylori, Riidinger, 97 ). (For further particulars about the stomach, compare Oppel, 96.)

The changes which the epithelium and the secretory cells of the stomach undergo during secretion are of special importance. These relations have been carefully studied in animals by R. Heidenhain (83). As far as our present knowledge goes, it would seem that the same processes also occur in man. In a state of hunger the chief cells of the fundus are large and contain numerous zymogen granules, while the parietal cells are small ; in certain cases the parietal cells abandon their mural position and, like the chief cells, border upon the lumen of the gland. During the first few hours of digestion the chief cells remain large, while the parietal cells increase in size. In the dog, from the sixth to the ninth hour of digestion, the chief cells diminish in size and contain fewer zymogen granules, while the parietal cells remain large and even increase in size. From the fifteenth hour on, the process becomes reversed; the

Fig. 212. From section through human pylorus; X6oo.

Fig. 213. Section through fundus of human stomach in a condition of hunger; X 5

Fig. 214. Section through fundus of human stomach during digestion ; X 5 chief cells enlarge and the parietal cells diminish in size. In a condition of hunger the cells of the pylorus are clear, of medium size, and do not begin to enlarge until six hours after feeding. From the fifteenth hour on, the cells become smaller and more turbid, while the nuclei return to the center of the cells. Since chemic examination has shown that the amount of pepsin found in the gastric mucous membrane increases with the enlargement of the chief cells of the body of the fundus glands, and decreases with their diminution in size, there can be hardly any doubt that this ferment is elaborated by these cells. It is assumed that the parietal cells secrete the acid of the gastric juice, although, in spite of all efforts, it has not yet been definitely proved that these cells possess an acid reaction.

Fig. 215. Illustrations of models, made after Born's wax-plate reconstruction method, of glandular structures and duodenal villi of the human intestine ; X Io : -'> Fundus gland; b, three pyloric glands; the one at the left is a simple tubular gland, the middle one a branched tubulo-alveolar gland ; the one at the right a typical pyloric gland of the branched tubular variety ; <-, leaf-shaped villi and crypts of Lieberkiihn of the duodenum ; d, crypts of Lieberkiihn of the large intestine.

The vascular and lymph-vessels of the stomach, and also its nerve supply, will be considered in a general discussion of these structures pertaining to the entire intestinal canal.

3. The Small Intestine

The mucous membrane of the small intestine is characterized by the presence of villi. The villi vary in size and shape in the different mammals. In man, in the upper portion of the small intestine, they are distinctly leaf-shaped, being three to four times as broad in one direction as they are in the other, often showing a narrowing at their bases. This has been shown by reconstruction of the mucosa and a number of villi from the duodenal region of a well-preserved human intestine. The villi are of columnar shape in the jejunum, and club-shaped in the ileum. The mucous membrane also forms permanent folds in both the duodenum and the remainder of the small intestine, the valvulae conniventes (Kerkring). Upon these the villi rest, and, indeed, it is probable that the very existence of the plicae is due to the blending of the basilar ends of the villi.

The epithelium of the intestinal mucous membrane covers the villi in a continuous layer, and penetrates into the mucosa to form the glands. Its structure is essentially the same in all regions of the small intestine, the cells being of the high columnar variety with free surfaces covered by wide, striated cuticular borders. The basilar portions of these cuticular borders are nearly always homogeneous, and upon vertical section give the appearance of a fine line. The cuticular borders of adjacent cells blend with each other, forming a continuous membrane, large areas of which may be detached from the villi (cuticula). The body of the ce.U consists of a fine fibrillar structure (spongioplasm) with the main threads parallel to long axis of the cell. This is more distinct in the free portions of the cell. In the interfibrillar substance are found fine granulesThe nuclei lie usually in the basilar third of the cells, and only where they show mitoses, as, for instance, in the tubular intestinal glands, do they pass to the free ends of the cells. The basal ends of the epithelial cells in the small intestine are also seen to be pointed, and the probability is that they rest upon the basement membrane. The question has, however, not been fully settled.

The epithelial cells undergo a special metamorphosis, after \vhich, by an increased production of mucus, they change into goblet cells. From recent investigations it would seem that any epithelial cell, whether it be situated upon the upper surface of a villus or deep down in one of the tubules of the intestinal glands, is capable of transformation into a goblet cell. The number of goblet cells is subject to great variation ; they are found singly in small numbers, or are very numerous, according to the stage of digestion and quantity of food in the intestine. The manner in which an ordinary epithelial cell changes into a goblet cell is very easily explained if the mechanical action on the cell caused by an accumulation of secretion be taken into consideration. As the secretion increases in quantity the upper portion of the cell becomes distended, and the remains of the protoplasm, together with the nucleus, are pushed toward the narrow base of the cell ; the cuticular zone is stretched, bulges into the lumen of the intestine, and is finally perforated, and perhaps even thrown off. In this way the cell loses its mucous secretion, collapses, and then appears as a thin, almost rod - like structure, with a long nucleus. It is the generally accepted theory that such an empty goblet cell may again assume the shape of an ordinary epithelial cell and repeat the process just described.

Leucocytes are sometimes found within the epithelial cells, but more usually between them, and according to Stohr (84, 89, 94), when seen in these positions, are in the act of migrating into the lumen of the intestine. That some of these cells actually pass into the lumen is probably true ; but as yet no leucocytes have ever been observed in the cuticula itself, and neither is the number

Fig. 216. Section through mucous membrane of human small intestine ; X 88. At a is a collapsed chyle-vessel in the axis of the villus.

the large intestine and rectum.

of cells found in the lumen of the intestine proportionate to the leuco cytes present in the epithelium. Since many are seen in the epithelium undergoing karyokinetic division, it is more probable that a part of them actually wander into the epithelium for the purpose of division (chemotaxis ?), only to return to the mucosa after the completion of the process (compare p. 61).

Into the spaces between the villi open numerous tubular glands. These are seldom branched, and are known as Lieberkiiliri 's glands, or crypts. Their length varies from 320 // to 450 //. They are regularly arranged in a continuous row, and often have an ampullalike widening of their lumina extending almost to the muscularis mucosae, but never quite reaching it. They are uniformly distributed not only throughout the small intestine, but also throughout

The cells lining the crypts of the small intestine are about one- half as long as those covering the villi ; a cuticular border is seen on the cells lining the upper part of the glands, but is absent in the cells lining the fundus of the glands. The cells are conical in shape, a condition probably due to the curvature of the glandular wall, the base of each cone lying toward the basement membrane, the apex toward the lumen of the gland a condition opposite to that found in the villi. Numerous goblet cells are also present. They vary only slightly in shape during mucous secretion, and do not, as in the villi, assume the form of goblets with distinct pedicles. Mitoses are always seen in the intestinal glands, especially in cells which do not contain mucin. They are readily distinguished, since

the nuclei in process of division, as we have seen, lie outside of the row formed by the remaining nuclei. The plane of division in these cells lies horizontal to the long axis of the gland, so that an increase in the number of cells results in an increase in the area of the glandular walls. Mitoses are very rarely observed in the epithelium covering the villi. If, therefore, any cells be destroyed on the surface of the villi, it must be assumed that the loss is replaced by new elements pushed up from the glands below (Bizzozero, 89, 92, I).

Fig. 217. Longitudinal section through summit of villus from human small intestine ; X 9 (Flemming's solution) : At a is the tissue of the villus axis ; b, epithelial cells ; c, goblet cell ; d, cuticular zone.

In the fundus of the crypts of Lieberkuhn of the small intestine are also found a variety of cells first described by Paneth, and known as the cells of Paneth. These cells contain granules which stain readily in eosin and in iron-lac-hematoxylin, and are no doubt cells which contain zymogen granules, cells which elaborate an enzyme. In the opossum the cells of Paneth are found not only in the crypts but also in epithelium of the villi intermixed with the columnar cells and goblet cells (Sidney Klein).

The entire duodenum, as well as that part of the pylorus in the immediate vicinity of the pyloric valve, is characterized by the presence of glands of a second type. In the duodenum these are seen intermingled with the glands of Lieberkuhn, and in the pylorus with the pyloric glands. These glands, Brnnner's glands, have a diameter of from 0.5 to I mm., and are branched tubulo-alveolar glands, with tubules provided with alveoli, especially along their lower portions. The bodies of the glands are situated principally in the submucosa, although a part may be in the mucosa. In the stomach they open into the gastric crypts, in the intestine either independently between the villi, or into the glands of Lieberkuhn. Here the glandular cells are in general similar to those of the pyloric glands, although, as a rule, somewhat smaller than the latter. The secretion of these glands is mucus (Bensley). Just as the duodenal glands extend into the stomach, so also the pyloric glands of the latter are found in the upper portion of the duodenum. Besides short villi, there are also present in the duodenum depressions of the mucous membrane analogous to the gastric crypts. The glands of Lieberkuhn begin at a certain distance from the pylorus ; at first they are short, and do not attain their customary length until a point is reached at which the pyloric glands extending into the duodenum finally disappear (yid. Fig. 218). It is therefore obvious that a transition zone exists between pylorus and duodenum, and that a distinct boundary line can not be drawn between the two, at least so far as the mucous membrane is concerned. The duodenal glands, as their name would indicate, are present only in the duodenum. Between the jejunum and ileum there is no distinct boundary, not even when microscopically examined. The differences are mostly of a quantitative nature ; in the jejunum the valvulae conniventes are more numerous than in the ileum, ancj the villi more slender and closer together. The glands of Lieberkuhn also appear to be more numerous in the jejunum.

The mucosa of the small intestine consists of reticular adenoid tissue containing mononuclear lymphocytes, polymorphonuclear leucocytes, and leucocytes with granular protoplasm. It supports the glands and extends into the villi whose axes it forms. The mucosa is separated from the glands, from the epithelium of the villi, as well as from that of the remaining surface of the intestine by a peculiar basement membrane.

Fig. ai8. Section through the junction of the human pylorus and duodenum ; X about 15 : At a the pyloric glands extend into the duodenum.

The latter somewhat complicates a proper histologic analysis, and as a consequence opinions regarding its structure and significance vary considerably. By some it has been described as a homogeneous, hyaline, and exceedingly fine membrane containing nuclei, by others as a lamella consisting entirely of endothelial cells. At all events, there are certainly nuclei in the basement membrane. Beneath the basement membrane is a marginal layer of a more fibrillar character. This is closelv associated with the mucosa, and may be regarded as a differentiation of the latter. Toward the muscularis mucosae the mucosa is terminated by a reticulated elastic membrane (F. P. Mall, in the dog), containing openings for the entrance of vessels, nerves, and muscle-fibers.

The muscularis mucosce consists of two layers of unstriped muscular fibers arranged in a manner similar to that in the external muscular tunic i. e., having an inner circular and an outer longitudinal layer. The fibers are frequently gathered into bundles, which appear to be separated from each other by connective tissue. From both layers, but more especially from the inner, muscle-fibers are given off at right angles, which enter the tunica propria and pass between the glands of Lieberkiihn, and even into the villi. In the latter these muscle-fibers are arranged in bundles, and lie

Fig. 219. Section of solitary lymph-nodule from vermiform appendix of guineapig, showing crypt ; X about 400 (Flemming's fluid).

near their axes around the lacteal vessels. The contraction of these fibers causes a contraction of the entire villus.

Lymph-nodules are distributed throughout the mucosa of the small intestine, occurring either singly, as solitary follicles, or aggregated, as Peyer's patches. At the points where they occur, the villi are absent and a lateral displacement of the glands of Lieberkiihn is observed. The lymph-nodule is usually pyriform in shape. The thinner portion protrudes somewhat in the direction of the lumen of the intestine, while the thicker portion extends outward to the muscularis mucosae, the latter being frequently indented or even perforated if the lymph-nodules be markedly developed. Their structure is similar to that of the lymph-follicles (see under these), and consists of reticular adenoid tissue, supporting lymph-cells. It should be remembered that every nodule may possess a germ center. Peyer's patches are collections of these lymph-follicles. The surface of the nodule presenting toward the lumen of the intestine is covered with a continuous layer of intestinal epithelium. In man the summit of that portion of the

Fig. 220. From colon of man, showing glands of Lieberkiihn ; X 2O nodule projecting into the lumen of the intestine presents but a slight depression of the intestinal epithelium, while in some animals (guinea - pigs), and especially in the nodules composing Peyer's patches, there is a deeper depression, even leading to the formation of a so-called "crypt" or "lacuna" (vid. Fig. 219). At the summit, the intestinal epithelium where it cornes in contact with the lymph-nodule, is peculiarly altered. In most cases there is an absence of a basement membrane, the epithelium resting directly upon the lymphoid tissue. No clearly defined boundary between the two is distinguishable (intermediate zone of v. Davidoff) ; they are therefore in the closest relationship to each other. The basal surfaces of the epithelial cells are fibrillar, the fibrils seeming to penetrate into the adenoid reticulum of the follicles.

4. The Large Intestine, Rectum, and Anus

The small intestine ends at the ileocecal valve. At some distance from the margin of the valve the villi of the ileum become broad and low. In the immediate vicinity of the valve their basilar portions become confluent, forming a honeycomb structure which supports a few villi. At the base of the honeycomb open the glands of Lieberkuhn. On the cecal side of the valve the villi become fewer in number and finally disappear, while the folds which give the honeycomb appearance persist for a considerable distance. In

Fig. 221. Transverse section of human vermiform appendix; X 20. Observe the numerous lymph nodules. The clear spaces in the submucosa are adipose tissue.

the adult cecum the villi are absent. The mucosa and glands present a structure similar to that of the remainder of the large intestine. In the mucosa of the vermiform appendix is found a relatively large number of solitary lymph-follicles, occasionally forming a continuous layer. The marked development of the lymph-follicles encroaches upon the glands of Lieberkuhn, so that many are obliterated ; they are penetrated by the adenoid tissue, the epithelial cells of the glands mingling with the lymph-cells. What finally becomes of the secretory cells has not been definitely ascertained (Riidinger, 91).

In the colon the villi are wanting, while the glands of the mucosa are densely placed and distributed with regularity.

The glands of Lieberkiihn in the colon are somewhat longer, and as a rule contain many more goblet cells than those in the small intestine. Only the neck and fundus of the glands show cells devoid of mucus. Transitional stages between the latter and the goblet cells have been observed in man (Schaffer, 91). Solitary lymph-follicles are found throughout the colon. They are situated in the mucosa, only the larger ones extending into the submucosa. The glands of Lieberkiihn are displaced in the regions of the lymphfollicles.

Fig. 222. A solitary lymph-follicle from the human colon : At a is seen a pronounced concentric arrangement of the lymph-cells.

The tanice and plica semilunarcs cease at the sigmoid flexure, and are replaced in the rectum by the plica transversales recti. Permanent longitudinal folds, the so-called columns rectales Morgagni, are present only in the lower portion of the rectum. Here the intestinal glands are longest but disappear simultaneously with the rectal columns. At the anus the mucous membrane of the rectum forms a narrow ring devoid of glands, covered by stratified pavement epithelium, and terminating in the skin in an irregular line. The transition from the mucous membrane to the skin is gradual, yet reminding one of the appearance presented at the junction of the esophagus with the cardiac end of the stomach.

External to the anus, and at a distance of about one centimeter from it, are numerous highly developed sweat-glands, the circumanal glands of Gay, which are almost as large as the axillary glands ; also sweat-glands of a peculiar type, in that they show a branching of the tubules (see Sweat-glands, under Skin).

5. Blood, Lymph, and Nerve Supply of the Intestine

In general, the following holds true with regard to the bloodvessels of the intestinal tract (further details will be discussed in dealing with the vessels of the various regions of the intestine) : The arteries enter along the line of the mesenteric attachment and penetrate the longitudinal muscular layer. Between the two muscular layers branches are given off which form an intermuscular plexus, from which, in turn, smaller branches pass out to supply the muscles themselves. The arterial trunks penetrate the circular muscular layer and form an extensive network of larger vessels in the deeper layer of the submucosa. This is known as Hellers plexus (F. P. Mall). From this, radiating branches are

Fig. 22 3- Section through fundus of cat's stomach. The blood-vessels are injected ; X given off which supply the muscularis mucosae, forming under the latter a close network of finer vessels. This plexus, together with that of Heller, gives rise to vessels which penetrate the muscularis mucosae and break up into capillaries in the mucous membrane. The veins of the mucous membrane form beneath the muscularis mucosae a plexus with small meshes, giving off many radiating branches ; these in turn unite to form an extensive network of coarser vessels. Veins extend from the latter and unite to form larger trunks, which then lie side by side with the arteries. According to F. P. Mall, delicate retia mirabilia occur here and there in the venous network in the submucosa of the intestine of the dog.

In the esophagus the arteries end in a capillary network situated in the mucosa and extending into the connective-tissue papillae of the mucosa.

The vessels of the stomach are arranged in plexuses in the muscular coat, submucosa, and beneath the muscularis mucosae, as previously described. From the plexus beneath the muscularis mucosse, small branches are given off which pass through this layer and in the mucosa form a capillary network, consisting of relatively small capillaries, which surround the gastric glands, this plexus being particularly well developed in the region around the body and neck of the glands, where the parietal cells are most numerous. The capillaries of this network are continuous with capillaries of a much larger size, forming a network surrounding the gastric crypts and situated immediately under the epithelium lining the mucosa of the stomach. The blood is collected from this capillary plexus by small veins which pass nearly perpendicularly through the mucosa, forming a plexus above the muscularis mucosae, from which small veins pass through the muscularis mucosae to the venous plexus in the submucosa.

The blood-vessels of the mucosa of the small intestine may be divided into (i) the arteries of the villi and (2) the arteries of the intestinal glands. The former arise principally from the deep arterial network in the submucosa, then penetrate the muscularis mucosae and give off branches at acute angles which continue without further branching into the summits of the villi. Within the villi themselves the arteries lie in the axes. The broader villi may contain two arteries. The circular muscle-fibers of the arteries gradually disappear inside of the villi (dog), and at the summit of the latter the vessels break up into a large number of capillaries. These form a dense network extending beneath the basement membrane and into its marginal layer. These networks give rise to venous capillaries which unite to form small vessels and finally end in two or more larger veins inside of the villi. These latter are connected with the venous network in the mucosa.

The glandular arteries, derived principally from the superficial network of the submucosa, also pass through the muscularis mucosae and break up internally into capillary nets which encircle the intestinal glands ; these give rise to small veins which empty into the venous plexus of the mucosa. The veins of the plexus in the mucosa unite to form larger branches, which connect with the plexus in the submucosa (compare Fig. 224). In the dog these trunks inside of the muscularis mucosae are encircled by bundles of muscle-fibers (sphincters, F. P. Mall). The capillaries of the solitary lymph-nodules do not always penetrate into the centers of the latter, but often leave a central nonvascular area.

The blood-vessels of the mucosa of the large intestine are, in their distribution, similar to the glandular vessels of the small intestine and stomach.

The lymph-vessels begin in the mucosa near the epithelium, pass down between the glands, and are arranged in the form of a network just above the muscularis mucosae, but with coarser meshes than that formed by the blood-vessels. Here the valves begin to make their appearance. The lymph-vessels pass through the muscularis mucosae and in the outer portion of the submucosa form a plexus with open meshes, from which are derived the efferent vessels which penetrate the muscular coat and thus gain access to the mesentery. In their course through the muscular coat they communicate with the branches of a plexus of lymph -vessels situated between the two muscular layers, and also with lymph-vessels found in the serous coat.

Fig. 224. Schematic transverse section of the human small intestine (after F. P. Mall).

The lymphatics of the small intestine begin in the axes of th'e villi. When filled, these lymph-vessels are conspicuous, irregularly cylindric capillary tubules, lined by endothelial cells, and known as the axial canals, the chyle-vessels, or the lacteals of the villi. They are hardly discernible when collapsed. If the villus be broad, it may contain two chyle-vessels, which then join at the apex of the villus, and may also be connected with each other by a few anastomoses. At the base of the villus the chyle-vessel enters a lymphatic capillary network, the structure of which is due to the confluence of similar canals. Numerous lymph-vessels from this network penetrate the mucous membrane in a vertical direction, uniting at the bases of the intestinal glands to form a second plexus subglandular plexus of the mucosa. A few of the lymph-vessels penetrating the mucous membrane directly perforate the muscularis mucosae to join the lymphatic network of the submucosa. The subglandular plexus also communicates with the submucous lymphatic plexus by means of small radiating branches (vid. Fig. 224). The solitary lymph-nodules themselves contain no lymphatic vessels, but are encircled at their periphery by a network of lymph capillaries. The same is true of the nodules in Peyer's patches. It is an interesting fact that in the rabbit lymph-sinuses exist around Peyer's patches, giving to the latter a still greater similarity to the nodules of lymph-glands. The solitary nodules of the same animal are not surrounded by the sinuses just mentioned (Stohr, 94) The structures of the alimentary canal receive their innervation mainly from sympathetic neurones, the cell-bodies of which are grouped to form small ganglia, located at the nodal points of two plexuses, one of which is situated between the two layers of the muscular coat, the other in the submucosa. These two plexuses are found in the entire digestive tract, although not equally well developed in its different regions. The outer plexus, the more prominent of the two, situated between the two layers of the muscular coat, is known as the plexus myentericus, or the plexus of Auerbach. It consists of innumerable small sympathetic ganglia, united by small bundles of nonmedullated fibers, containing here and there a much smaller number of medullated nerve-fibers. The cell-bodies of the sympathetic neurones of this plexus are grouped to form the sympathetic ganglia. The dendrites, the number of which varies for the different cells, divide and redivide in the ganglia, some extending into the nerve bundles uniting the ganglia. The neuraxes of the sympathetic neurones of the ganglia form nonmedullated nerve-fibers, which leave the ganglia by one of the several roots possessed by each ganglion, and, after repeated division and forming intricate plexuses in the circular and longitudinal layers of the muscular coat, terminate on the involuntary muscle-cells of these layers.

Fig. 225. A portion of the plexus of Auerbach from stomach of cat, stained with methylene-blue (infra vitani), as seen under low magnification.

The plexus in the submucosa, known as the plexus of ' Meissner, is similarly constructed, although it contains fewer and much smaller ganglia and the meshes of the plexus are much finer. It communicates by numerous anastomoses with the plexus of Auerbach. The neuraxes of the sympathetic neurones of this plexus have not been traced, with any degree of certainty, to their terminations. Numerous nonmedullated nerves enter the muscularis mucosae and, according to Berkley (93, I), form in the dog terminal bulbs and nodules which perhaps represent the endings of motor (sympathetic) nerves in this layer. Nerve-fibers have also been traced into the mucosa, and in the vicinity of the glands and in the villi are found numerous exceedingly fine nerve-fibers which interlace, but in the greater por"tion of the intestinal tract the endings of these fibers have not been fully worked out. That they end on the glandcells seems very probable from observations made by Kytmanow (96), who was

able, by means of the methylene-blue method, to stain plexuses of fine nerve-fibrils surrounding the gastric glands of the cat, some of these fibrils being traced through the basement membrane of the glands and to and between the gland-cells, where they terminated in clusters of small nodules on both the chief and parietal cells. The plexus of Meissner is not so well developed in the esophagus as in the remaining portions of the digestive tract.

That the cell-bodies of many of the sympathetic neurones of Auerbach's and Meissner's plexuses are capable of being stimulated by cerebrospinal nerves seems certain from observations made by Dogiel (95), who has shown that many small medullated nervefibers which enter the digestive tract through the mesentery (small and large intestines) terminate after repeated division in terminal end-baskets which surround the cell-bodies of many of the sympathetic neurones of these plexuses. Similar nerve-fibers ending in baskets have also been observed in the ganglia of the plexuses of the stomach and esophagus. Large medullated nerve-fibers, the dendrites of sensory neurones, have also been traced to the alimentary canal. In the esophagus these pass to the mucosa, where, after repeated division, they lose their medullary sheaths, the nonmedullated terminal branches forming a subepithelial plexus from which terminal, varicose branches, further dividing, enter the stratified epithelium and may be traced to near the surface of the epithelium.

Fig. 226. From thin section of esophagus of cat, showing the epithelium and a portion of the mucosa and the terminal nerve-fibrils in the epithelium (from preparation of Dr. DeWitt).

Large medullated nerve-fibers may be traced through the ganglia of Auerbach's and Meissner's plexuses in the stomach and intestinal canal and through the nerve bundles uniting these ganglia (Dogiel, 99), but the termination of these fibers has not been determined. In the large intestine of the cat they have been traced to the epithelium and between the epithelial cells covering the mucosa (Huber).

6. The Secretion of the Intestine and the Absorption of Fat

The cells of Brunner's glands are similar in many respects to those of the pyloric glands. They form, as has been shown, a mucous secretion, and present in their various physiological activities, structural changes which are similar to the structural changes presented by the cells of other mucous glands under similar conditions (Bensley). It is well known that the goblet cells of the intestinal glands are very numerous during starvation, and that they nearly disappear after continued functional activity ; furthermore, they entirely disappear in certain portions of the rabbit's intestine after pilocarpin-poisoning. It would therefore appear that t*he principal physiologic function of the glands of Lieberkuhn is to secrete mucus, although the possibility of the production of another secretion, especially in the small intestine, must not be excluded (compare R. Heidenhain, 83), especially since it has been shown that the cells of Paneth probably elaborate an enzyme.

Until recently it was believed that the fat contained in the food was emulsified in the intestine, and furthermore that the bile acted upon the cuticular margins of the epithelial cells in the villi in such a manner that an assimilation of the emulsified fat by the cells of the villi (not by the goblet cells) was made possible. It has been repeatedly observed that the epithelial cells contained fat granules during absorption. Hence a mechanism was sought for which would account for an assimilation of globules of emulsified fat on the part of the cells. It seemed most probable that protoplasmic threads (pseudopodia) were thrown out from each cell through its cuticular zone, which, after taking up the fat, withdrew with it again into the cell. But when it was shown that, after feeding with fatty acids or soaps, globules of fat still appeared in the epithelial cells as before, and that the chyle also contained fat, the hypothesis was suggested that the fat is split up by the pancreatic juice into glycerin and fatty acids, and that the fatty acids are then dissolved by the bile and the alkalies of the intestinal juice, only again to combine with the glycerin to form fat within the epithelial cells. It remains for the histologist to ascertain the exact mechanism in the cell which changes the fatty acids into fat. Altmahn (94) claims that certain granules of the cells (elementary organisms) offer a solution to this problem. The manner in which the fat globules gain access to the lacteal vessels of the villi is a question which has not as yet been settled definitely ; it would appear, however, that the leucocytes play an important part in this transfer, since in preparations of the intestinal mucosa, taken from an animal fed on a diet rich in fat milk diet and stained in osmic acid, numerous leucocytes containing black granules or globules may be observed in the lacteal vessels and in the spaces of the adenoid reticulum of the villi.

D. The Liver

In the adult the liver is a lobular, tubular gland with anastomosing tubules. When viewed with the unaided eye or under low magnification the liver is seen to be composed of a large number of nearly spheric divisions of equal size ; this is particularly noticeable in some animals, especially in the pig. These divisions are the liver lobules and have a diameter of from 0.7 to 2.2 mm. They are separated from each other by a varying amount of interlobular connective tissue, which is a continuation of the capsule of Glisson, a fibro-elastic layer surrounding the entire liver and covered for the greater portion by a layer of mesothelium. In the interlobular septa are found the larger blood-vessels, bile passages, nerves and lymph-vessels. On examining a thick section of the liver with a low power, a radiate structure of the lobule is noticeable, and an open space is seen in its center, which according to the direction of the section, is either completely surrounded by liver tissue or con* nected with the periphery of the lobule by a canal. This open space represents the central or intralobidar vein of the lobule which belongs to the system of the inferior vena cava. From the center of the lobule toward its periphery extend numerous radiating strands of cells, which branch freely and anastomose with each other, and are known as the trabeculce, or cords of hepatic cells. Between the latter are small, clear spaces occupied partly by blood capillaries and partly by the intralobular connective tissue. The above description is in some respects not a true statement of the appearance presented by the human liver, as in the latter one or more lobules may blend with each other, thus rendering the individual lobules less distinct.

Fig. 227. Section through liver of pig, showing chains of liver-cells ; X 7

Fig. 228. Section through injected liver of rabbit. The boundaries of the lobules are indistinct ; X about 35.

The hepatic cords consist of rows of hepatic cells. The cells are usually polyhedral in form, with surfaces so approximated that a cylindric capillary space, known as the bile capillary remains between them. The angles of the cells also show grooves which join those of the neighboring cells to form canals in which lie the blood capillaries. A closer examination of the hepatic cells reveals the fact that they possess no distinct membrane, and, in a resting state, usually contain a single nucleus, although some possess two. It is an interesting fact that nearly all the hepatic cells of some animals as, for instance, the rabbit contain two nuclei. The cell-bodies of the hepatic cells, which average from 18 p to 26 // in diameter, show a differentiation into protoplasm and paraplasm. This is especially manifest in a state of hunger. In this condition it is seen that the network of protoplasm around the nucleus is unusually dense, and becomes looser in arrangement as it extends toward the periphery of the cell-body. The paraplasm is slightly granular, and contains glycogen and bile drops during the functional activity of the cell (secretion vacuoles). The vacuoles in the paraplasm play an important part in the secretion of the cell, and are due to the confluence of minute drops of bile into a large globule. As soon as the vacuole has attained a certain size it tends to empty its contents into the bile capillary through a small tubule connecting the vacuole with the bile capillary (Kupffer, 73, 89).

Fig. 229. Human bile capillaries. The capillaries of one lobule are seen to anastomose with those of the adjoining lobule (below, in the figure) ; X JI (chrome-silver method).

Fig. 230. Human bile capillaries as seen in section ; X 4^o (chrome-silver method).

The bile capillaries are, as we have remarked, nothing but tubular, capillary spaces between the hepatic cells, with no distinct individual walls, although the outer portions of the liver cells (excplasm) are somewhat denser than the remainder of the cells, and serve to form a wall for the bile-capillaries. They may be compared to the lumen of a tubular gland, although in the human liver their walls consist of. only two rows of hepatic cells. In the lower vertebrates the walls of the bile capillaries appear in transverse section to consist of several cells (in the frog generally three, in the viper as many as five). The bile capillaries naturally follow the course of the hepatic cords i. c., in man extending radially. They form networks, the meshes of which correspond to the size of the hepatic cells. At the periphery of the lobule the hepatic cells pass directly over into the epithelial cells of the smaller interlobular bile-ducts. The epithelium of the latter is of the cubical variety, its cells being considerably smaller than the hepatic cells. At the point

where the hepatic cells become ^-cxN ^S\ Bile capillaries, continuous with the walls of the smaller passages we find a few cells of gradually decreasing size which represent a transition stage from the cells of the bile capillaries (hepatic cells) to those of the interlobular bile passages.

Fig. 231. Schematic diagram of hepatic cord in transverse section. At the left the bile capillary is formed by four cells, at the right by two ; the latter type occurs in the human adult.

Fig. 232. From the human liver, showing the beginning of the bile-ducts ; X 90 (chrome-silver).

The vascular system of the liver is peculiar in that, besides the usual arterial and venous vessels common to all organs, there is found another large afferent vein the portal vein. It arises from a confluence of the superior and inferior mesenteric, the splenic, coronary veins from the stomach, and cystic veins. It divides into two branches, the right supplying the right lobe of the liver, the left the remaining lobes. These branches again divide into numerous smaller branches, the smallest of which finally reach the individual lobules. Along its whole course through the interlobular connective tissue the portal vein and its branches are accompanied by divisions of the hepatic artery and bile passages. In a transverse section of the liver the arrangement of these structures in the interlobular tissue is such that the cross-sections of the vessels belonging to the hepatic vein are seen to be at some distance from the closely approximated branches of the portal vein and bile passages. Branches of the portal vein encircle the liver lobules at different points, and while they remain within the interlobular connective tissue, are known as interlobular veins. From these, small offshoots are given off to the lobules which, on entering, divide into capillaries and form a closely reticulated network between the hepatic cords. The meshes of this network are about as large as an hepatic cell, each cell coming in repeated contact with the blood capillaries. All of these capillaries pass toward the central or intralobular vein of the lobule, which during its efferent passage through the lobule continues to receive capillaries from the portal system. The intralobular veins unite to form the sublobular veins,situated in the interlobular connective tissue, and these unite to form the larger hepatic veins which empty into the inferior vena cava. The hepatic artery is of much smaller size than the portal vein. It is distributed in the main to the connective tissue of the liver and to the bile-ducts, breaking up into branches which are situated in the interlobular connective tissue. The terminal capillaries form small venules which communicate with the interlobular branches of the portal system. Whether the capillaries of the hepatic artery pass as such into the hepatic lobules is difficult to say, since injection masses forced into the hepatic artery pass over into the terminal branches of the portal vein and vice versa. This question needs, therefore, further investigation. The smaller divisions of the hepatic artery constitute, therefore, internal radicals of the portal vein, since they are within the liver itself. The relations of the various blood-vessels within the lobule are in themselves somewhat difficult of comprehension, but the whole becomes still more complicated when the reciprocal relations of the vessels and bile capillaries are taken into consideration. In order to understand the structure of the liver lobule, with its hepatic cords, vessels, and bile capillaries, the following points should be borne in mind : The course of the bile capillaries is along the surfaces, and that of the blood-vessels along the angles of the hepatic cells ; every cell comes in contact with a bile capillary and a blood capillary. The latter, however, do not come in contact with the former, but in man are separated by at least half the breadth of a hepatic cell. In animals in which the bile capillaries are bounded by more than two cells, the blood-vessels extend along the outer .sides of the hepatic cells ; here the bile and blood capillaries are separated from each other by the breadth of a whole cell.

Fig. 233. Injected blood-vessels in liver lobule of rabbit ; X Ioa

Fig. 235. Reticulum (Gitterfasern) of dog's liver; X I2 (gold-chlorid method).

The connective tissue within the hepatic lobules presents points of interest which, however, are not demonstrable in organs treated by ordinary methods. But when the liver tissue is treated by a certain special method (see page 307), an astounding number of fibers are seen extending in regular arrangement from the periphery toward the central vein. These fibers are extremely delicate, of nearly equal size, and intermingle in such a manner as to form an enveloping network about the blood capillaries (Gitterfasern ; Kupffer ; Oppel, 91 ; vid. Fig. 235). A few coarser fibers (radiate fibers, Kupffer, 73) seem to enter in a less degree into the formation of the sheath around the blood capillaries ; they also extend from the periphery toward the center of the lobule and form a coarse reticulum, the meshes of which are drawn out radially. The radiate fibers are less prominent in man, but are numerous and well developed in animals (rat, dog). With what exuberance the intralobular connective tissue may develop, is seen in the accompanying sketch of a sturgeon's liver, which is taken from one of Kupffer's preparations. The Gitterfasern of Kupffer are, as has been shown by F. P. Mall, reticular fibrils, presenting the same characteristics as similar fibrils found in other regions.

Fig. 236. Connective tissue from liver of sturgeon. At a is an open space from which the hepatic cells were mechanically removed during treatment.

Certain peculiar cells the so-called stellate cells of Kupffer (76) occur in the lobule, and are seen only after a special method of treatment. They are uniformly distributed, of different shapes, elongated, and end in two or three pointed projections. They are smaller than the hepatic cells, and contain one or two nuclei.

In a recent communication Kupffer (99) states that the stellate cells belong to the endothelium of the intralobular capillaries of the portal vein. These capillaries, which are, according to their development, sinusoids (Minot), form in all probability a syncytial lining (Kupffer) consisting of thin continuous lamellae, the protoplasm appearing as a network of threads, with nucleated masses of protoplasm at nodal points of this network. In places where this protoplasm is present in larger quantity and contains round or oval nuclei it is more readily brought out with special stains, and appears in such preparations in the form of structures to which the name stellate cells has been given. In such cells blood corpuscles and fragments of such were often found. The endothelium of these capillaries possesses, therefore, a phagocytic function, taking up particles of foreign matter, blood-corpuscles, etc.

The efferent ducts of the liver, the bile-ducts, are lined by columnar epithelium, varying in height in direct proportion to the caliber of the passage. The smallest ducts possess a low, the medium sized a cubical, and the larger a columnar epithelium. The smaller bile-ducts have no clearly defined external walls other than the membrana propria ; the larger ones, on the other hand, possess a connective-tissue sheath which may even present two layers in the larger passages. Unstriped muscular fibers occur in the large ducts, and also small mucous glands. The gall-bladder consists of a mucous, fibre-muscular, and, where covered by the peritoneum, of a subserous and serous coats, as has recently been shown by Sudler, whose account is here followed.

Fig. 237. From preparation from the liver of a rabbit, showing the so-called stellate cells of Kupffer : a, Stellate cells; b, liver cells.

The mucous coat is covered by a single layer of columnar epithelium, with nuclei situated in the basal portions of the cells. The epithelial cells rest on a poorly developed muscularis mucosa::. The mucosa presents folds, covering ridges of connective tissue of the fibre-muscular layer, and contains small lymph-nodules, and a varying number of small mucous glands. The fibro- muscular layer consists of interlacing bands of nonstriated muscle and fibrous connective tissue, and is not arranged in distinct layers. The subserous and serous coats present the same appearance as in other regions of the peritoneum. The artery or arteries going to the gall-bladder divide into branches which form capillaries in the mucosa under the epithelium ; these are most numerous in the folds above mentioned. The lymphatics form a subserous and submucous plexus.

The lymphatics accompany the portal vein and hepatic artery, also the branches of the hepatic vein (Wittich). They form a network in the interlobular connective tissue. The lymphatics form further a superficial network in subserous layer of the peritoneum. The superficial lymphatics and the lymphatics accompanying the vessels are in communication.

Within the lobules, the lymphatics occur as perivascular spaces, as was first shown by MacGillavry. F. P. Mall, who has recently studied the origin of the lymphatics in the liver, summarizes his results as follows : The lymphatics of the liver arise from perilobular lymph-spaces, and these communicate directly with perivascular lymph-spaces ; the lymph reaches these spaces by a process of filtration through openings which are normally present in the capillary walls of the liver

Fig. 238. Part of a section through liver lobule from dog, showing stellate cells; X i68.

Berkley (94) has described several divisions of the intrinsic nerves of the liver, all connected and morphologically alike. These nerves are no doubt the neuraxes of sympathetic neurones, the cell-bodies of which are located in ganglia outside of this organ. No medullated fibers were found by him, although it seems probable that the nerve-fibrils terminating between the cells of the bile-ducts (see below) are terminal branches of sensory nerve-fibers. The nerves of the liver accompany the portal vessels, the hepatic arteries, and the bile-ducts. The' first division of the nerves, embracing the larger number of the intrinsic hepatic nerves, accompany the branches of the portal vessels, form plexuses about them, and end in interlobular and intralobular ramifications, the latter showing here and there knob-like terminations on the liver-cells, and, in their course, give off here and there branches which end on the portal vessels.

The nerve-fibers following the hepatic arteries are in every respect like the vascular nerves in other glands. Some of the terminal branches seem, however, to end on hepatic cells. The nerve-fibers following the bile-ducts may be traced to the smaller and medium-sized ducts, forming a network about them, and ending here and there in small twigs on the outer surface of the cells, and occasionally, it would seem, between the epithelial cells lining the ducts. The suggestion seems warranted that these terminal fibrils are the endings of sensory nerves. Some of the nerve-fibers following the bile-ducts may be traced into the hepatic lobules. The intralobular plexus is formed, therefore, by the terminal branches of the nonmedullated nerve-fibers accompanying the portal and hepatic vessels and the bile-ducts. In the wall of the gall-bladder are found numerous small sympathetic ganglia formed by the grouping of the cell-bodies of sympathetic neurones (Dogiel). The neuraxes of these innervate the nonstriated muscle of this structure. Large, medullated nerve-fibers may be traced through these ganglia which appear to end in free sensory endings in and under the epithelium lining the gall-bladder (Huber).

In the human embryo the liver originates from the intestine during the second month as a double ventral diverticulum. Later solid trabecular masses are developed which then unite and become hollow. At this stage the whole gland is uniform in structure, as a division into lobules does not take place until later. The bile capillaries are surrounded by more than two rows of cells. In this stage the embryonal liver suggests a condition which is permanent during the life of certain animals. Only later when the venae advehentes, which later represent the branches of the portal vein, penetrate the liver, is there a secondary division into lobules (about the fourth month), by which process the primitive type gradually changes to that characteristic of the adult.

E. The Pancreas

Like the liver, the pancreas is an accessory intestinal gland, and originates as a diverticulum of the intestine. It remains in permanent communication with the intestine by means of its duct the pancreatic or Wirsungian duct. The pancreas is composed of numerous microscopic lobules, surrounded by connective tissue which penetrates into the lobules and between the alveoli and is accompanied by vessels and nerves. The secretory portion of the organ may be regarded as a compound, branched alveolar gland, the general structure of which is shown in Fig. 240, the alveoli forming the principal portion of the gland. The epithelial walls of the alveoli consist of a number of secretory cells, whose appearance varies according to the functional state of the organ. The basilar portions of the cells present a homogeneous protoplasm, while those parts of the cells bordering upon the lumen are granular. The relation of these zones to each other depends upon the physiologic condition of the gland ; during starvation the internal or granular zone is wide and prominent ; after moderate secretion the cells become as a whole somewhat smaller, the granules decrease in number, and the outer or protoplasmic zone increases in size. After prolonged secretion there is an entire absence of the granules, and the whole cell apparently consists of homogeneous protoplasm. It is therefore probable that during a state of rest peculiar granules (zymogen granules) are formed at the expense of the protoplasm, and that these granules represent a preliminary stage of the finished secretion. During the functional activity of the gland the granules gradually disappear, while the fluid secretion simultaneously makes its appearance in the lumen, although the granules have as yet never been observed in the lumen itself. After secretion the cell grows again until it reaches its original size, only again to begin the formation of zymogen granules. Whether the cells of the gland are destroyed or not during secretion is still a matter of uncertainty, but does not seem probable.

Fig. 239. Transverse section through alveolus of frog's pancreas.

Fig. 240. Model of lobule of human pancreas (Maziarski, "Anatomische Hefte," 1901).

An intermediate tubule similar to those of the salivary glands connects with each alveolus, and then passes over into a short intralobular duct. This is lined, as in the salivary glands, with columnar epithelial cells, which are not, however (at least in man), striated at their basal ends. The intralobular ducts merge into excretory ducts, which finally empty into the pancreatic duct. The epithelium of the excretory ducts is simple columnar in type. Goblet cells are seen only in the pancreatic duct.

Fig. 241. From section through human pancreas ; X about 200 (sublimate).

In the secreting alveoli small protoplasmic, polygonal, and even stellate cells are often seen, the so-called centro-acinal cells, or cells of Langerhans. The significance of these structures is not fully understood. Langerhans himself supposed that they belonged to the walls of the excretory ducts. This interpretation seems warranted by the fact that it has been found that the secreting cells of the alveoli are directly joined to the low cells of the intermediate tubules. When the alveoli lie closely packed together, the adjoining intermediate tubules fuse and are reduced to one or, at most, a few cells. As a result a condition is seen within the alveolar complexus, especially when the excretory ducts are in a collapsed state, closely resembling the structures seen by Langerbans. Peculiar cells, wedged in here and there between the secretory cells, but resting on the membrana propria, have also been observed. They undoubtedly are sustentacular cells of the gland (cuneate cells, Podwyssotzki, 82).

The incinbrana propria of the alveoli is probably homogenous. Immediately adjoining it is another delicate but firm membrane, consisting of fibrils whose structure in many respects resembles that of the reticular fibers (Gitterfasern) in the liver and spleen, but which are here in relation to the alveoli (Podwyssotzki, 82).

In warm- and cold-blooded animals, groups of cells differing in arrangement, size, and structure from the secretory cells, are found among the gland tubules and alveoli of the pancreas ; these are known as the intcrtubular cell-masses, or areas of Langerhans. They are most numerous in the splenic end of the pancreas (Opie). They consist of slightly granular cells, smaller than the secretory cells of the alveoli, arranged in the form of anastomosing trabeculae, with irregular spaces, varying in size, separating the trabeculae. Dogiel (93) has shown that in a well-preserved human pancreas treated by the chrome-silver method, in which the gland ducts even to their finest intra-alveolar branches were well stained, no ducts were found in the areas of Langerhans. Such areas are, in the human pancreas, usually separated from the surrounding gland tissue by a small amount of connective tissue. They possess a blood supply, consisting of relatively large capillaries found in the spaces formed by the trabeculae of cells above mentioned. The areas of Langerhans have been variously interpreted. They have been looked upon as small areas of gland tissue in process of degeneration, or again as areas of embryonic gland tissue. From their structure and distinct blood supply, and the fact that no ducts have been traced into these areas, it seems probable that they are small masses of cells forming a secretion which passes into the blood-vessels internal secretion.

Fig. 242. From section through human pancreas ; X45 (sublimate).

Fig. 243. Scheme showing relation of three adjoining alveoli to excretory duct, illustrating origin of centro-acinal cells.

Fig. 244. From section of human pancreas, showing gland alveoli surrounding an area of Langerhans.

The blood-vessels after entering the gland, divide into smaller branches in the lobules, and finally break up into capillaries which encircle the secreting alveoli. The blood-vessels do not follow the course of the ducts so regularly as in the salivary glands (Flint). The meshes of the capillary network are not all of the same size. In some regions they are so wide that quite large areas of the alveoli are without blood-vessels.

The nerves of the pancreas have been investigated by Cajal and Sala (91) and Erik Muller (92), who find in this gland large numbers of nonmedullated nerve-fibers, some coming from sympathetic ganglion cells situated in the pancreas and others entering from without. The nonmedullated nerve-fibers form plexuses surrounding the excretory ducts and end in periacinal networks. Fibrils from the network about the alveoli were traced to the secretory cells. A portion of the nonmedullated nerves in the pancreas form perivascular plexuses.

The development of the pancreas is peculiar in that the larger portion, together with the duct of Santorini, originates from the dorsal intestinal wall, and a smaller portion from the ductus choledochus. The latter part, with its accessory pancreatic duct, fuses with the former, after which there is a gradual retrogression of the duct of Santorini, so that finally the entire secretion of the pancreas almost invariably flows into the pancreatic or Wirsungian duct.


The oral mucous membrane may be fixed with corrosive sublimate or alcohol, stained in bulk, and examined in cross-section. If special structures, such as glands, nerves, or the distribution of mitoses, are to be examined, special methods must be adopted.

Teeth. In order to obtain a general- view of the structure of the teeth, the latter must be macerated and ground as in the case of bone.

The relations of the hard and soft parts in undecalcified teeth are best studied by the use of Koch's petrifaction method.

The teeth may also be examined in section, and when decalcified are treated as bone. Hydrochloric acid, dilute chromic acid, and picric acid dissolve the enamel prisms, their cement-substance being the first to disappear (von Ebner, 91).

The enamel of young teeth stains brown in a solution of chromic acid . or its salts, and blackens in osmic acid. In the enamel cells, globules are seen, which are stained in osmic acid. If longitudinal sections of the enamel be corroded with hydrochloric acid, the cruciform arrangement of the enamel prisms is plainly seen.

The fibrils of the dentin may be demonstrated by decalcifying a tooth in the fluid recommended by von Ebner, the teeth of young individuals being well adapted for this purpose. Occasionally carious teeth also show the fibrils plainly. Corrosion with hydrochloric acid produces the same result.

The cementum, especially that part lacking in cells, contains a large number of Sharpey's fibers.

The development of the teeth is studied in the embryo ; the jaw-bone is fixed, decalcified, and cut in serial sections. The most convenient material is a sheep embryo, which can almost always be had from the slaughter-house.

Taste-buds. To study the taste-buds of the tongue and the relations which their constituent cells bear to each other, fixation in Flemming's fluid is recommended. The orientation of the taste-buds must be very carefully done, after which exactly longitudinal or transverse serial sections are made (not thicker than 5 /j.) and stained with safraningentian-violet.

The nerves in the taste-buds are brought out either by Golgi's method, the methylene-blue method, or by the use of gold chlorid. If the last be used the procedure is as follows : A papilla foliata of a rabbit is removed with a sharp razor and placed for ten minutes in lemon juice, then in gold chlorid for from three-quarters of an hour to one hour, after which the specimen is placed in water weakly acidulated with acetic acid (5 drops to 100 c.c. of water) and exposed to the light. As soon as reduction has taken place the specimen is treated with alcohol and cut in vertical sections. These may be treated for a short time with formic acid (in which they swell slightly), washed with water, and mounted in glycerin.

In certain objects, such as the nictitating membrane of the frog, certain lobules of the rabbit's pancreas (the latter being so thin as to be especially well adapted for microscopic examination), etc., the glandular structure may be examined in normal salt solution.

Glands of the Digestive Tract. Microscopically, the glands present varying pictures according to the phase of secretion in which they are fixed. Specimens in the different stages may be obtained either by feeding and then killing the animal after a definite period, or by irritating certain nerves, or finally by the use of certain poisons especially adapted to this purpose, such as atropin and pilocarpin. In the rabbit, for instance, i c.c. of a 5% solution of pilocarpin hydrochlorate or i c.c. of a 0.5% solution of atropin sulphate is used for each kilogram of the animal's weight. In atropin- intoxication secretion is suppressed, while in pilocarpin -poisoning it is increased. By this method cells are obtained either full of secretion or containing no secretion at all.

Sections should be made from carefully selected material which has been fixed either in Flemming's solution or corrosive sublimate, although fixation with strong alcohol also gives instructive pictures.

In preparations fixed with Flemming's solution the crescents of Gianuzzi stain somewhat more deeply than the remaining cells of the alveoli, and in objects that have been treated with alcohol or corrosive sublimate and then stained with hematoxylin the crescents take on a very deep color. The intermediate tubules of the salivary glands also assume a deeper stain with hematoxylin and carmin. The intralobular tubes are particularly well defined by certain stains, as for instance when Congo red is used after staining with hematoxylin ; other acid anilin stains may also be used. The intralobular tubes of most salivary glands (not, however, of the parotid of the rabbit nor of the sublingual of the dog) are stained a dark -brown color (calcareous reaction) by agitating small, fresh pieces of tissue in order to facilitate the entrance of air, and then treating them with a dilute aqueous solution of pyrogallic acid. The stain persists for some time in specimens preserved in alcohol. Sections made by free hand from tissues treated by this method give excellent results.

Mucin is soluble in dilute alkalies, as for instance lime-water, and may be precipitated from these solutions by the addition of acetic acid, although the precipitate does not redissolve in an excess of acetic acid ; mucin is also precipitated by alcohol, but not by heat. Mucinogen does not stain with hematoxylin, as does mucin. By this latter test a gland in a state of functional activity may be differentiated from one at rest (R. Heidenhain, 83). After treatment with alcohol, safranin stains mucin orange-yellow. For the demonstration of mucin, more especially in alcoholic preparations, H. Hoyer (90) has recommended thionin or its substitute, toluidin-blue. Indeed, the basic anilin dyes in general seem to have a particular affinity for mucin.

P. Mayer (96) recommends the following two solutions for the staining of mucin : (i) Mucicarmin Carmin i gm., aluminium chlorid 0.5 gm., and distilled water 2 c.c. are stirred together and heated over a small flame till the mixture becomes quite dark. As soon as the mixture has attained the consistency of thick syrup, 50% alcohol is added and the whole transferred to a bottle in which it is shaken after the addition of more alcohol. Finally, still more 50% alcohol is added until the whole amounts to too c.c. Before using, this stock solution is diluted tenfold with tap-water rich in lime-salts. (2) Muchematein : (#) Aqueous solution 0.2 gm. of hematein is ground in a mortar containing a few drops of glycerin ; to this are added o. i gm. aluminium chlorid, 40 c.c. glycerin, and 60 c.c. distilled water. (t>~) Alcoholic solution 0.2 gm. hematein, o.i gm. aluminium chlorid, 100 c.c. 70% alcohol, and i or 2 drops of nitric acid. Both of these solutions are used for staining mucin in sections and thin membranes. By the use of these methods the mucous acini of mixed glands are shown with ease and precision. Under favorable conditions the whole secretory and excretory system of the gland may be brought out by Golgi's method (see this).

In order to obtain a general structural view of the esophagus a small animal may be selected, in which case small pieces of tissue are fixed and imbedded in paraffin. If a large animal is used, the tissue is imbedded in celloidin.

The mucous membrane of the stomach should be fixed while still fresh and warm, the best fixative for this purpose being corrosive sublimate. Mixtures of osmic acid are also serviceable, but fixing with corrosive sublimate increases the staining power of the tissue. In order to preserve the stomach and intestine in a dilated condition, they should be filled with the fixing fluid and after ligation placed whole in the fixing agent.

In gastric mucous membrane that has been fixed either with corrosive sublimate or alcohol, the parietal cells are easily differentiated from the chief cells by staining. The most reliable and convenient method is as follows : Sections fastened to the slide by the water-albumin fixative method are stained with hematoxylin and then placed in a dilute aqueous solution of Congo red until they assume a red color (minutes); they are then washed with dilute alcohol until the parietal cells appear red and the chief cells bluish (Stintzing). Almost all acid anilin dyes have an affinity for the parietal cells ; hence the red stains may be combined with hematoxylin and the blue ones with carmin. The chief cells then take the color of the carmin or hematoxylin, and the parietal cells that of the anilins.

An accurate fixation of that portion of the small intestine possessing villi is attended with great difficulty, since the axial tissue of the villi shows a tendency to retract from the epithelial layer surrounding it (the latter becoming fixed first); and as a consequence spaces are formed at the summits of the villi which undoubtedly represent artefacts. A good method is to cut pieces from tissue while still warm and fix in osmic acid. If portions of the intestine be filled with alcohol or corrosive sublimate and thus dilated, both the glands and villi are shortened. The methods above mentioned for staining mucin may be used to stain the goblet cells. The villi may also be examined in a fresh condition in one of the indifferent fluids. For this purpose the intestine of the mouse is especially well adapted.

The absorption of fat is best studied in preparations fixed in osmic acid, and especially in those treated by Altmann's method.

The technic for the solitary lymph-follicles and Peyer's patches is the same as that for lymph-glands. For this purpose the cecum of a rabbit or guinea-pig is the best material.

The nerves of the intestinal mucous membrane are best demonstrated by means of the methylene-blue method or Golgi's method (vid. Technic), and the coarser filaments of Auerbach' sand Meissner's plexuses may also be stained by the gold method (Lowit's procedure, p. 48). Good results are also obtained by staining with hematoxylin such specimens as have been previously fixed and distended with alcohol. The plexuses then appear somewhat darker than the remaining tissue of the isolated mucous membrane or muscular layer.

Liver. The arrangement of the liver lobules is best seen in the pig's liver. In the human liver and in most domestic animals the lobules are not sharply defined, two or three adjacent lobules merging into each other. In the liver of the fetus, of the new-born, and of children, the lobules are seen indistinctly or not at all, although the perivascular spaces of the blood-vessels are better seen than in the adult.

The liver-cells are best examined by treating small pieces of tissue with i cjo osmic acid or osmic mixtures ; in the latter case subsequent treatment with pyroligneous acid is necessary. Good results can also be obtained by fixing with corrosive sublimate and staining with hematoxylin (after M. Heidenhain).

In order to see the glycogen in the liver-cells Ranvier (89) proceeds as follows : A dog is fed on boiled potatoes for two days, after which sections of its liver are cut with a freezing microtome and examined in iodized serum. In a short time the glycogen is stained a wine-red. If the preparation be now exposed to osmic acid vapor, the stain will remain fixed for from twenty-four to forty-eight hours. Glycogen is insoluble in alcohol and ether, and stains a port wine-red in iodin solutions ; the color disappears when the specimen is warmed, but returns again on cooling.

The distribution of the hepatic blood-vessels is usually demonstrated by injection of the portal vein, as the injection of the hepatic artery does not, as a rule, give such satisfactory results.

The injection method is also employed for the demonstration of the bile capillaries. Chrzonszczewsky recommends the following so-called physiologic autoinjection : A saturated aqueous solution oif indigo-carmin is injected into the external jugular vein three times in the course of one and one-half hours (dog 50 c.c. each time, cat 30 c.c., full-grown rabbit 20 c.c.). The animal is then killed and small pieces of its liver fixed in absolute alcohol or in potassium chlorate ; in the latter case a saturated solution of the salt may be injected into the blood-vessels. A subsequent injection of the blood-vessels with carmin -gelatin may also be employed and the whole liver then hardened in alcohol. By this method the bile capillaries finally become filled with the indigo-carmin by a gradual elimination of the substance from the blood- and lymphvessels and passage through the cells into the biliary system, while the blood-vessels themselves are distended by the carmin-gelatin. In the frog, the demonstration of the biliary passages is more easily accomplished by injecting 2 c.c. of the indigo-carmin solution into the large lymphsac and killing it after a few hours. The liver is then fixed in the manner described above and is then ready for further treatment.

The bile passages may also be injected directly through the hepatic duct or the ductus choledochus. For this purpose it is best to use a concentrated aqueous solution of Berlin blue (Berlin blue that is soluble in water). The results obtained by this method are not, however, always satisfactory, and even in the best of cases only the peripheral portions of the liver lobules are successfully injected.

The bile capillaries may be impregnated with chrome-silver. Fresh pieces of liver tissue are placed for two or three days in a potassium bichromate-osmic acid solution (4 vols. of a 3% bichromate of potassium solution and i vol. of i% osmic acid) and then transferred to a -75% aqueous solution of silver nitrate. After rinsing in distilled water the specimens are cut with a razor, the sections again washed with distilled water, placed for a short time in absolute alcohol, cleared in xylol, and finally preserved in hard Canada balsam. Both celloidin and paraffin imbedding are admissible, but either process must be hurried, as the preparation always suffers under such treatment. In the finished specimen, the bile capillaries appear black by direct light.

Another method which brings to view more extensive areas of the bile capillaries is as follows : A piece of liver tissue from a freshly killed animal is fixed in rapidly ascending strengths of potassium bichromate solution (from 2% to 5%). After three weeks the specimen is placed in a 0.75% silver nitrate solution, when after a few days (very marked after eight days) the bile capillaries, if examined in sections, will appear black by direct light (Oppel, 90).

Sometimes the bile capillaries are brought out in preparations treated by the method of R. Heidenhain, although only small areas are colored and these not constantly. The application of other stains, as for instance the method of M. Heidenhain following the gold chlorid treatment, often results in the staining of small areas of bile capillaries.

In all the methods used for the demonstration of the bile capillaries, whether physiologic autoinjection, direct injection, or impregnation, the secretion vacuoles of the liver-cells are clearly brought to view.

By treating pieces of liver tissue according to the method of Kupffer (76) the connective tissue of the liver, especially the reticular structure {Gitterfaserri) , is shown. Fresh liver tissue is cut with the double knife and the thinnest sections placed for a short time in a 0.6% sodium chlorid solution or in a 0.05% solution of chromic acid. From this they are transferred to a very dilute solution of gold chlorid (Gerlach) (gold chlorid i gm., hydrochloric acid i c.c., water 10 liters), and kept for one to several days in the dark until they assume a reddish or violet color. If the staining has been satisfactory (which is by no means always the case), the reticular fibers, and occasionally also the stellate cells, are seen. Instead of the double knife the freezing microtome may be used and the method continued as stated (Rothe).

The reticular fibers are seen under more favorable conditions by using the following method, recommended by Oppel (91): Fresh pieces of tissue fixed in alcohol are placed for twenty-four hours in a o. 5 % aqueous solution of yellow chromate of potassium (larger pieces in stronger solutions up to 5%), then washed with a very dilute solution of nitrate of silver (a few drops of a 0.75% solution to 30 c.c. distilled water), and transferred to a 0.75% solution of silver nitrate. In twenty-four hours the intralobular network surrounding the blood capillaries will have become stained. The best areas lie at the periphery of the specimen, and extend about i mm. into the parenchyma. Free-hand sections are made, or the specimens are quickly imbedded in celloidin or paraffin, to be cut afterward by means of the microtome. The same results are obtained by placing small fresh pieces of the tissue for two or three days in a 0.5% chromic acid solution and then one or two days in a 0.5% solution of silver nitrate. The further treatment is as in the preceding method.

The method of F. P. Mall is also employed in the examination of the hepatic connective tissue.

The following method is recommended by Berkley for demonstrating the nerves of the liver : Small pieces of liver tissue from 0.5 to i mm. in breadth are placed in a half-saturated aqueous solution of picric acid for from fifteen to thirty minutes, and .then in TOO c.c. of potassium bichromate solution that has been saturated in the sunlight and to which 16 c.c. of 2% osmic acid has been added. The specimens now remain in this fluid for forty-eight hours in a dark place, and at a temperature of 25 C. After this the tissue is treated with a 0.25% to 0.75% aqueous solution of silver nitrate for five or six days, washed (quick imbedding may be employed), cut, cleared in oil of bergamot, and mounted in xylol-Canada balsam.

The cellular elements of the pancreas may be examined without further manipulation in very thin lobules from the rabbit (Kiihne and Lea).

There are various methods of differentiating the inner and outer zones of the cells. In sections of the tissue fixed in alcohol, carmin stains the outer zone of the cells more intensely than the inner (R. Heidenhain, 83). For the staining of the inner zone, fixation in Flemming's fluid is to be recommended, then staining with safranin, and finally washing in an alcoholic solution of picric acid. The granules of the inner zone (zymogen granules) appear red. These also stain red with the Biondi-Ehrlich mixture. The simplest and most precise method of demonstrating the zymogen granules is that of Altmann. The secretory and excretory ducts of the pancreas are shown, as in the case of the salivary glands, by the chrome-silver method.

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A Textbook of Histology (1910): Introduction To Microscopic Technic | General Histology | I. The Cell | II. Tissues | Special Histology | I. Blood And Blood-Forming Organs, Heart, Blood-Vessels, And Lymph- Vessels | II. Circulatory System | III. Digestive Organs | IV. Organs Of Respiration | V. Genito-Urinary Organs | VI. The Skin and its Appendages | VII. The Central Nervous System | VIII. Eye | IX. Organ of Hearing | X. Organ of Smell | Illustrations - Online Histology

Reference: Böhm AA. and M. Von Davidoff. (translated Huber GC.) A textbook of histology, including microscopic technic. (1910) Second Edn. W. B. Saunders Company, Philadelphia and London.

Cite this page: Hill, M.A. (2020, January 25) Embryology Book - A textbook of histology, including microscopic technic (1910) Special Histology 3. Retrieved from,_including_microscopic_technic_(1910)_Special_Histology_3

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