?3?e. J^s 'O LlB^i ;#> TfVEt c; «, s-sl &9t CORNELL UNIVERSITY. THE Bostoell |l. Wlamtx Cibrarg THE GIFT OF ROSWELL P. FLOWER FOR THE USE OF THE N. Y. STATE VETERINARY COLLEGE. 1897 Cornell University Library QM 551.D91 Histology; normal and morbid. 3 1924 001 036 544 The original of this book is in the Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://archive.org/details/cu31924001036544 HISTOLOGY: NORMAL AND MORBID. BY EDWARD K. DUNHAM, Ph.B., M.D., PROFESSOR OF GENERAL PATHOLOGY, BACTERIOLOGY, AND HYGIENE IN THE UNIVERSITY AND BELLEVUE HOSPITAL MEDICAL COLLEGE, NEW YORK. ILLUSTRATED WITH 363 ENGRAVINGS. LEA BROTHEKS & CO., NEW YORK AND PHILADELPHIA. 1898. ±^ £""/< I Entered according to Act of Congress in the year 1898, by j~s * . LEA BROTHERS & CO., ' in the Office of the Librarian of Congress, at Washington. All rights reserved. ELECTROTYPED BY WESTOOTT &. THOMSON, PHILADA. PRESS OF WILLIAM J, DORNAN, PHILADA. PREFACE. In presenting to the student of medicine so condensed a volume upon normal and morbid histology an explanation of the author's purpose may, perhaps, not be amiss. It appears to the writer that the most important lesson to be derived from a study of the tissues in health and in disease is a knowledge of the constant and potent activities of the cells to which those tissues owe both their origin and usefulness. When the body develops under normal conditions those cells build up the tissues, gradually modifying their formative activities so as to oc- casion a diversity of structure in the various parts of the body. During this developmental epoch, and after maturity is attained, the activities which are grouped as functional, and which it is the lot of the tissues to maintain, are also carried on by the cells. But in order that these manifold cellular activities shall be of the usual or " normal " character, the conditions under which they are carried on must not depart greatly or for any considerable length of time from a certain usual, but rather indefinite standard. If those conditions are materially altered, the cellular activities become modified, and the functions they perform suffer aberration, as a result of which structural changes in the cells and tissues may ensue. It is this close relation between cellular activity and structure which unifies the subjects usually kept distinct under the titles of normal and pathological histology, for it is evident that there is no natural separation between those subjects. In the preparation of this manual the author has steadfastly kept in view such a conception of the relations between cellular activity and structure. To carry out this purpose it did not appear neces- sary to describe the various changes wrought in the individual organs or tissues by unusual conditions. It seemed to him that a general statement of the alterations in structure attributable to 3 4 PREFACE. modified cellular activity would enable the student to interpret such departures from the normal as he might observe in particular speci- mens, provided he was familiar with the normal structures of the body. In this belief the writer has devoted most of his space to a description of the normal structures, and has contented himself with only a brief account of the histology of the more prevalent morbid processes. He was encouraged in this course by the con- sciousness that in individual cases the application of the principles involved might be more successfully made by the instructors under whose guidance these studies were pursued. For the sake of clear- ness, however, examples of morbid structure have been selected from various parts of the body to illustrate the different phases of the processes that were being outlined. Those histological methods and data which are utilized for the purpose of clinical diagnosis have been almost entirely omitted, be- cause they are fully described in special works on that subject and are not strictly within the limits assigned to this more elementary book. Occasional reference has been made to technical journals on his- tology. Those which contain abstracts of the current literature on that subject, and which will, therefore, be of greatest use to the student, are : The Jour mil of the Royal J\ficroscoj>ica/ Society, Zeit- schrift fi'ir wixnenschaftliclie Jlikroxkopie, and Ventralblatt fur , primitive ectoderm, surface view ; c, primitive entoderm ; d, dividing cell of tin' ectoderm, (van Bencden.) cells are derived from those of the primitive ectoderm, but the 22 INTRODUCTION. primitive entoderm may also participate in its formation. Tins third layer is called the mesoderm. Soon after its formation, the mesoderm divides at the sides of the embryo into two layers — a parietal, which joins the under surface of the ectoderm, and a vis- ceral, attached to the upper surface of the entoderm. The space between these two layers is occupied by fluid, and is destined to form the future body-cavities. In the axis of the embryo the three earlier layers remain in continuity, forming a cellular mass around the site of the future spinal column (Fig. 4). Fig. 4. Embryo of Necterus in cross-section. (Piatt.) ect., ectoderm ; mend., mesoderm ; end., ento- derm ; a, neural groove ; ch, situ of future spinal column. From these three embryonic layers of cells the body of the fetus is developed. The entoderm, with the visceral or lower layer of the mesoderm, turns downward and inward to meet its fellow of the opposite side and form the alimentary tract. The ectoderm and parietal or upper layer of the mesoderm also turn downward and in- ward, outside of the alimentary tube, and join those of the other side to form the walls of the body. Meanwhile, the upper surface of the ectoderm over the axis of the embryo becomes furrowed. The edges of this furrow grow upward, deepening the groove between them, and finally arch over it and coalesce, forming a canal around which the central nervous system is developed (Fig. 5). Traces of this canal persist through life as the central canal of the spinal cord and the ventricles of the brain. The embryonic layers have a deeper significance than the mere furnishing of the architectural materials from which the body is built up. They are evidences of a distinct differentiation in the development of the cells of which they are composed. The ecto- derm gives rise to the functional part of the nervous system and to the epithelial structures of the skin and its appendages. The cells of the mesoderm elaborate the muscular tissues and that great group INTB 01) UCTJON. 23 known as the connective tissues, and the entoderm contains the cells that build up the linings of the digestive tract, including its glands, and of the respiratory organs. It appears, then, that this division of the cells of the embryo into three layers marks a dis- tinct difference in the destinies of the cells composing those layers. This distinction persists through life, the tissues arising from a given layer showing, in general, a closer relationship to each other than the tissues arising from different layers. But this relationship is nut always revealed by a similarity in structure, for the latter is determined by the functions the tissues are destined to perform, and tissues of like function acquire a similarity in structure. Thus, for example, the neuroglia in the central nervous system resembles Fir;. 5. Cross-section of fish embryo. (Ziegler.) u, neural canal, cells enclosing it not represented; b, chorda dorsalis, site of future spinal column; cto, aorta ; Bf, external layer of meso- derm ; l', c, body-cavity ; d, alimentary canal, not yet completely closed * *, passes through the external layer of the mesoderm to its inner surface ; e, deutoplasm, or yolk of egg. some of the connective tissues, although one develops from the ectoderm and the other from the mesoderm ; and the ganglion cells of the central nervous system differ greatly in structure from the epithelium of the skin, nails, etc., and the cells of the neuroglia, notwithstanding the fact that they all spring from the cells of the ectoderm. The explanation is to be sought in the similarity of the usefulness of neuroglia and connective tissue and the difference in the functions of ganglion cells and those of the other tissues eman- ating from the ectoderm. During the early stages of development the cells of the germinal layers are very similar in character, although, as we have seen, their potential qualities are quite diverse. As growth proceeds, they begin to vary in size, shape, and internal structure in the dif- 24 INTRODUCTION. ferent parts of the foetus. Their relative positions become modi- fied. The primitive organs are denned and the tissues of which they are composed become elaborated. The elaboration of the tissues is wrought by the cells, which dis- play what is called their formative powers in the production of materials of various sorts which lie between them, and are called the intercellular substances. The amount and kind of intercellular substance vary, each form of tissue having its own peculiarities in this respect, dependent upon the rdle it is to play in the general economy. Some of the tissues perform functions which require the active processes that can be carried on only in cells, and in these the intercellular substances are either small in amount and appar- ently structureless, as in epithelium, or their place is taken by a tissue of separate origin, while the cells, relieved of the necessity for exercising their formative powers in this direction, become highly specialized to meet the functional demands imposed upon them. This development is met with in the muscular and nervous tissues. Other tissues of the body are of use mainly because of their physical properties, such as rigidity, elasticity, tensile strength, plia- bility, etc. These tissues, collectively called the connective tissues, are essentially passive. They require little or no cellular activity for the performance of their functions, and it is in the elaboration of these tissues that the cells exercise their most marked formative powers during the development of the body, causing the deposition of intercellular substances which possess the requisite physical char- acters—rigidity and elasticity in the case of bone, pliability and ten- sile strength in the case of ligamentous structures, etc. As these substances are perfected, the cells decrease in activity, until they merely preside over the integrity of the intercellular substances they have already produced. It may be well to point out here a distinction that divides the tissues of active cellular function into two groups. The first group, including the various modifications of epithelium, displays its ac- tivity in the elaboration of material products, taking the form of either new cells which are continually being produced, or of certain chemical substances which appear as a secretion. The second group, comprising the muscular and nervous tissues, exercises its functional activities in the storage of latent energy in such sub- stances of unstable chemical nature and in such a manner that it INTS, 01) UCTION. 25 can be liberated when required and directed toward the accomplish- ment of some definite purpose. The functions of both groups require an active intracellular metabolism, resulting in the forma- tion of particular chemical substances. In this they are alike. But in the first group the production of those substances is, in itself, the functional purpose of the process, while in the second group those substances are merely a means for holding energy in the latent condition. If we may so express ourselves, the first group utilizes energy for the elaboration of material, the second group elaborates material for the utilization of energy. In the adult, under normal conditions, each kind of cell, if it reproduce at all, gives rise to cells only of its own kind. But when the conditions are morbid, a sort of reversion may take place, the progeny of a given cell then showing less evidence of specialization than the parent cell. Such reverted cells, or their descendants, may never develop into more specialized cells, or they may regain the original degree of specialization possessed by the first cell, or, fin- ally, they may become specialized along some divergent line of devel- opment, giving rise to a tissue that is nearly or remotely akin to that from which they started, according to the degree of reversion which has taken place. The reversion appears never to extend further back than the degree of specialization that is marked by the formation of the three embryonic layers in the history of devel- opment; for example, epithelium which springs from either the entoderm or ectoderm does not revert to a primitive condition from which it can develop into bone or some other form of connective tissue normally derived from the mesoderm. Examples of rever- sion will be met with in the chapters on Inflammation, Tumors, and Metaplasia. PART I. NOEMAL HISTOLOGY. CHAPTEE I. THE CELL. As has been stated in the introductory chapter, the cells of the body are not all alike. Most of them have undergone modifications fitting them for the performance of some definite function, and the majority of them are in consequence not appropriate objects for a study of the general characters of a cell. The extent to which this modification has affected the visible structure of the cell is, how- ever, very different in the different tissues, and in some of them the cells retain so much of their original embryonic appearance as to closely resemble the unspecialized cell. This is true of the cells of some varieties of epithelium. But, though in appearance they give little evidence of specialization, in their functional activities they display very marked modifications of the powers of the primitive cell. Some of those powers, perhaps the nutritive, perhaps the secretory, have become exaggerated, while others, e. g., the locomotory, or reproductive, have fallen into abey- ance, or suffered almost total extinction. On the other hand, it is obvious that such cells as constitute the whole body of unicellular animals must retain all the powers essen- tial to a living cell in relatively equal states of development. No one of them can be extinguished or thrown out of its proper bal- ance with resj>ect to the others if the cell is to remain normal. And yet, even among the unicellular organisms, certain parts of the cell may be very evidently specialized for the performance of par- ticular functions. For example, the cilia of infusoria have the power of executing much more rapid movements than the other 27 28 NORMAL HISTOLOGY. parts of the same cell. And it is probable that all protozoa, i. e. unicellular animals, possess similar, though less obvious and in- ternal, heterogeneity of constitution. The less the degree of specialization or differentiation in the structure of an organism, the less highly developed is the functional activity of which it is capable, and the less perfect its ability to cope with possible unfavorable environment. The value to the whole organism of a diversity in its parts is, therefore, unquestion- able, and the higher we go in the animal kingdom, the greater we find the development of this diversity, coupled with a more and more perfectly adjusted co-operative interdependence of the differ- ent parts of the body. In the protozoa the single cell does all the work of the whole organism. In the multicellular animals, the metazoa, this work is distributed among the component cells of the body, each of which has developed an efficiency for performing its special work that would be incompatible with a wider range of duties. It is quite impossible to find in nature any example of a cell devoid of all individual peculiarities attributable to differentiation or specialization. We must, therefore, study several varieties of Fig. 6. Amceba pellucida. (Frenzel.) a, ectoplasm ; 6, endoplasm ; c, nucleus ; d, nucleolus ; e, large contractile vacuole ; /, incorporated foreign body ; g, g, pseudopodia. cell in order to gain an ideal conception of such a cell. This accom- plished, we may consider those cells which occur in nature as special modifications of that type. Perhaps the simplest cell leading an independent existence is the protozoon, amoeba (Fig. 6). This animal is widely distributed in THE CELL. 29 moist earth, upon the surfaces of aquatic plants, and in the soil at the margins of ponds and sluggish streams. The body of the amoeba consists of a gelatinoid substance which has received the name protoplasm, or, more definitely, cytoplasm. Within this cytoplasm and sharply defined from it is a round or oval, vesicular body, called the nucleus, which in turn contains one or more particularly conspicuous granules, the nucleoli. The most superficial layer of the cytoplasm appears perfectly clear, colorless, and homogeneous. It envelops the rest of the cyto- plasm, which has a granular appearance. The clear peripheral portion is distinguished as the " hyaloplasm," or " ectoplasm ;" the granular internal portion as " spongioplasm," or "endoplasm." The terms hyaloplasm and spongioplasm are also used in a different and more restricted sense, as will presently appear. When viewed under the microscope, the granules of the cyto- plasm are seen to possess a constant, slight, vibratile motion, the Brownian movement, to which is added now and then a flowing movement from one part of the cell to another. At intervals there is a protrusion of the ectoplasm at some point, extending for some distance from the body of the cell, a pseud opodium. This may soon be retracted again, merging with the rest of the ectoplasm, or some of the endoplasm may flow into the central portion of the pseudo- podium, converting it into a broad extension of the cell-body. This may subsequently be withdrawn, or the whole mass of cytoplasm, with the nucleus, may flow into the pseudopodium, gradually in- creasing its size, until the whole cell occupies the original site of the pseudopodium. In this way the animal executes a slow, creeping locomotion. These pseudopodial movements and the locomotion occasionally incident to them appear to be wholly spontaneous, i. e. dependent upon internal conditions of which we have no knowledge. They may, however, be influenced by external circumstances. Certain sub- stances evidently attract the amoeba, others are either matters of in- difference to it or repel it. If a pseudopodium comes in contact with some particle in the surrounding medium, it may retreat from it, appear indifferent to it, or be attracted and proceed to incorporate it. This is accomplished by the cytoplasm flowing around the for- eign body and coalescing on its further side so as to enclose it. It is then conveyed to the body of the cell, either by cytoplasmic cur- rents, by the withdrawal of the pseudopodium containing it, or 30 NORMAL HISTOLOGY. by the streaming of the cell-body into that protrusion. The fate of the particle thus incorporated depends upon its nature. If it be serviceable as food, it is gradually digested and ab- sorbed, or such parts of it as are digestible are so utilized, and the remainder, no longer of use to the amoeba, is extruded from its body. These phenomena reveal powers of perception and selection on the part of this cell which are very closely akin to the intelligence of more complex organisms. They also demonstrate its power of assimilating material from without, to serve as nourishment and the source of the energy which it expends in executing its movements and in carrying on the chemical processes pertaining to its internal economy. At intervals, there appears within the endoplasm a small, clear, spherical spot. This gradually increases in size and constitutes a little drop of fluid, sharply defined from the surrounding cytoplasm. After it has attained a certain size, it suddenly disappears, the cyto- plasm around it coalescing and leaving no trace of its existence. Such a clear space, filled with fluid, within the body of a cell is called a vacuole, and those which are suddenly obliterated, contrac- tile vacuoles. Their purpose is not clearly understood, but prob- ably has to do with a primitive circulatory or respiratory function, since contractile vacuoles are not observed in the cells of higher organisms where those functions are carried on by more elaborate mechanisms. Eventually the amoeba reproduces its kind by dividing into two similar cells, each of which grows into a likeness to the parent individual. Let us now compare the amoeba with some other varieties of cell, in order to learn what they all have in common. The amoeba has an outer, soft, transparent layer of cytoplasm, the ectoplasm. This is not present in all cells. In many the granular cytoplasm has no envelope, but appears to be quite naked. In other varieties it is enclosed in a distinct membrane. In the great majority of cells the active streaming of the cyto- plasm and the pseudopodial protrusions described in the amoeba are wanting, but the Brownian movement of the granules is more con- stantly present. The cells have fixed positions and their food is brought to them, usually in solution, so that the more active move- ments so essential to the welfare of the amoeba would be superfluous. THE CELL. 31 For a similar reason, as already intimated, they can dispense with the contractile vacuole. We learn, then, that when we reduce the cell to its simplest terms, it consists of a mass of cytoplasm enclosing a nucleus. To these we must probably add a third essential constituent, the centro- some, which is a minute granule situated in the cytoplasm. It is so small that its presence has not been established in all cells, its detec- tion in many cells being extremely difficult because of the general granular appearance of the cytoplasm in which it lies. It plays such an important part, however, in the division of those cells in which it has been studied, that the inference that it is an essential part of all cells appears justified. These three constituents, the cytoplasm, nucleus, and centrosome, appear to be the essential organs of a cell among which its activities are distributed (Fig. 7). We do not know how they do their work, Fig. 7. Schematic diagram of a cell : a, ectoplasm composed of hyaloplasm ; &, spongioplasm ; e, chromosome, composed of "chromatin," and forming a part of the intranuclear reticu- lum ; between these chromatic fibres is the acbromatin ; d, hyaloplasm in the meshes of the spongioplasm ; e, one of the two nucleoli represented in the diagram ; /, one of eight bodies constituting the metaplasm represented ; g, centrosome, with radiate arrangement of the surrounding spongioplasm ; ft, nuclear membrane. but we have a general conception of the distribution of the work performed by the whole cell among these three organs. 32 NORMAL IIISTOLv the spindle, remaining uncolored or only faintly tinged l>v nuclear dyes, while i he uprights, made up of the chromo- somes, are deeply stained. The ends of the chromosomes now unite to form a thread, and (he wreath-like arrangement gradually passes into that of the dispirem. 5. Dispirem (Figs. 14 and 17). — The halves of the original chro- ttioplasm of the nucleus are now arranged in two skeins about the poles. From these the two daughter-nuclei of the future cells are formed (Fig. IS). Fig. 17. Fig. 18. Fig. 17.— Dispirem In this case the polar bodies have 11.it divided (compare Fig. 111). Fig. 18.— Daughter-nuclei which have nearly reached their full development. Centrosomes present in the cytoplasm. In these figures the structure of the cytoplasm is not given. During metakinesis the cytoplasm of the cell begins to show signs of division. This may be accomplished through a constric- tion of the body of the cell, which gradually becomes deeper and finally severs the two portions; or a series of punctiform or short THE CELL. 39 linear enlargements of the lines of the achromatic spindle appear in its equator, and through these a plane of cleavage, dividing the two new cells from each other, is finally established. It is rarely that any biological process assumes such mathemat- ical precision as is displayed in karyokinesis. The purpose of that mode of cell-division appears to be an exactly equal partition of all parts of the chromoplasm between the young cells. Whether the amount of cytoplasm given to the daughter-cells is the same or different, the division of the chromoplasm is exactly equal, not only in its whole bulk, but each chromosome, which appears to be the morphological unit of the chromoplasm, is split into exactly equivalent halves, one of which is contributed to the formation of each daughter-nucleus. It is for this reason that the chromoplasm is looked upon as the carrier of hereditary peculiarities. After the formation of the daughter-nuclei, the ceutrosome usually passes from it into the cytoplasm. It may divide earlier than has been described, the division taking place while it exists as the polar body, or even earlier (Fig. 16). A cell nearly always divides to form two new cells, but some- times three or more cells may be produced, the chromosomes being distributed among them (Fig. 19). Such cases are probably Fig. 19. Epithelial cell from a carcinoma. (Galeotti.) The centrosome has divided into four portions, and the chromosomes are arranged with reference to these. The figure represents the meta- kinetic phase of karyokinesis, which will result in the formation of four imperfect nuclei. always morbid, and the resulting cells are not wholly the equiv- alents of the parent cell. It occasionally happens that the cytoplasm fails to divide after the formation of the daughter-nuclei, and cells with two or more nuclei result. When the nuclei continue to multiply and the 40 NORMAL HISTOLOGY. cytoplasm increases in amount, but dues not suffer division, large multinucleated cells are produced, which have been called " giant- cells." They occur normally in the marrow of bone and are pro- duced in many of the inflammatory processes. The direct or amitotic method of cell-division is inaugurated by an active change in the shape of the nucleus, which may have pre- viously increased in size and become richer in chromoplasm. The nucleus becomes constricted and finally separated into two portions, which are not necessarily equally rich in chromoplasm. The cyto- plasm, either at the same time or later, becomes similarly con- stricted until it is divided into two parts, each containing one of the nuclear divisions (Figs. 20, 21, 22). Ftg. 20 Fig. 21. Fig. 22. Amitotic cell-division. (Flemming.) Epithelial cells from the bladder of a salamander. Figs. 20 and 21 contain nuclei with constrictions dividing them into nearly equal portions. Fig. 22.— Contiguous cells, each containing a nucleus about half the size of those prevailing in the tissue, and, therefore, probably the result of cell-division by the direct process. It is believed that this mode of division does not result in the formation of cells that have the complete character of the parent- cell, and that their descendants form a degenerate race that is destined to extinction. It is quite obvious that no such precise partition of the chromatic substance is likely to take place as that which is characteristic of karyokinesis, and if the chromosomes are really the carriers of hereditary peculiarities, this mode of division can hardly favor their perfect transmission. CHAPTER II. THE ELEMENTARY TISSUES. The various parts of the body are composed of a small number of " elementary tissues." Each of these elementary tissues has a definite structure, but the detailsof that structure may vary within certain lim- its in different parts of the same mass or in different situations within the body. Such variations can usually be referred to differences in the functional activity assigned to the tissue, which is not always exactly the same throughout the body. For example, epithelium is an ele- mentary tissue consisting of cells which are nearly always rich in cytoplasm and are separated from each other by a very small amount of homogeneous intercellular substance. Wherever epithelium is found it has these general peculiarities of structure. But the func- tions demanded of epithelium are of widely diverse character in different situations, and its structure shows a corresponding diversity in its details. The fact that it is made up almost exclusively of cells leads to the natural inference that the usefulness of epithelium depends upon cellular activities.' Inasmuch as these may be of very different character, we should expect the tissue to vary chiefly in the structure and arrangement of its component cells according to the particular activity which was needed and the manner in which it was utilized. Such, as a matter of fact, is the case. These considerations will be made clearer if we follow a little more closely the example offered by epithelium. In some situations epithelium serves to protect the underlying tissues from injury. But the usual injurious influences which threaten the tissues differ in different parts of the body, and must, therefore, be averted by different means. Upon the sur- face of the skin they are chiefly of a mechanical or chemical nature, and to resist them the cells of the epithelium forming the epidermis undergo a modification in structure, resulting in the formation of a superficial horny layer which is highly resistant to abrasion and chemical change. Upon the inner surfaces of the 41 42 XORMAL HISTOLOGY. respiratory passages the conditions are different. Here the tissues require protection from particles of dust that may be inhaled. For this purpose the epithelial cells lining those passages are provided with minute, hair-like processes, "cilia," which execute lashing move- ments toward the outlets of the passages and occasion the transpor- tation of substances coming into contact with them toward the outer world. In the digestive tract the conditions are again differ- ent. The tissues underlying the epithelial lining need protec- tion from the chemical action of the fluids in the stomach and intes- tine, as well as from friction with their solid contents. The cells of the epithelium meet these needs by a secretion of mucus, which is discharged upon the inner surfaces of the digestive organs, where it serves as a protective layer and as a lubricant. In other situations epithelium has an excretory function, which is less clearly of value in protecting its immediate surroundings, but is essential for the protection of the whole organism from substances which would exert an injurious effect if they were permitted to ac- cumulate in the circulating fluids of the body. These substances are absorbed from those fluids by epithelial cells, from which they are discharged from the body either unchanged or after transforma- tion into other chemical compounds. Here the most obvious prod- ucts of cellular activity are of no use in the economy, and are elim- inated from it ; but it is not improbable that the cells which separate them or their antecedents from the circulating fluids may also discharge useful substances into those fluids (" internal secretion "). We must not assume that the most obvious function exercised by a tissue is the only service it does to the organism. The epithelium which carries on this eliminative function is nearly always associated with other elementary tissues to form an organ, called a "gland," in which the epithelium is the functionally active tissue, the other tissues being subservient to it. The glands of the body differ considerably in both structure and function, but in all of them it is epithelium which elaborates the materials essential to the formation of their normal secretions. Mention has already been made of those glands which furnish secretions charged with waste materials to be eliminated from the body. Such glands are called excretory glands, and are exemplified by the kidney. Other glands, distinguished as secretory in a restricted sense, furnish secre- tions which are of service to the organism. Examples of such glands are those which discharge their secretions into the alimentary THE ELEMENTARY TISSUES. 43 tract where, by virtue of the ferments they contain, they prepare the food for absorption. Another example of a secretory gland is furnished by the sebaceous glands of the skin, which produce an oily substance serving to keep the epidermis upon which it is discharged soft and pliable. In the secretory glands the cells of the functional epithelium elaborate within their bodies the substances necessary to give the glandular secretion its peculiar and useful characters. These sub- stances accumulate within the cells, -where they are stored until required, when they are discharged into the secretion. While in the stored condition within the cells these substances may have a different chemical constitution from that which they acquire when they are discharged from the cells. A simple example of this chemical transformation is furnished by the liver, in the epithelial cells of which carbohydrates are stored as glycogen, to be liberated as a closely related chemical substance, glucose. In like manner the ferments stored in the epithelial cells of the digestive glands are not fully formed while in that situation, but exist in states known as " zymogens," from which the potent ferment appears to be readily formed when the cells are called upon to furnish it. It is apparent, then, that the elementary tissue, epithelium, can- not have the same microscopical structure in all the situations in which it is found ; but, notwithstanding these variations, wherever epithelium occurs it presents certain general structural peculiarities which are constant and which distinguish it from the other element- ary tissues. Similarly, each of the other elementary tissues pre- sents variations in the details of its structure in different situations, but always retains certain general structural characteristics dis- tinguishing it from all the other elementary tissues. It is the first task of the student of histology to learn to recognize and identify these elementary tissues wherever they occur and however they may vary from the type which is first presented to him for study. In the following chapters an attempt is made to give the student an idea of the essential structure of the elementary tissues, so that he may recognize them in specimens which he examines with the microscope. For this purpose they have been arranged in the order of their structural simplicity. When examining a specimen under the microscope with a view to recognizing the elementary tissues it contains, the student should habitually ask himself the following questions : (1) What are the 44 NORMAL HISTOLOGY. general characters of the cells entering into the structure of the tissue ? (2) What kind of intercellular substances separates those cells? (3) How are the cells arranged with reference to each other and the intercellular substances? Correct answers to these three questions will enable him to quickly determine the nature of the tissue he is observing, even if it should vary considerably in struct- ural details from examples of the same tissue with which he has already become familiar. CHAPTER III. THE EPITHELIAL TISSUES. 1 I. ENDOTHELIUM. General Characters. — (1) The cells possess thin membranous bodies, except at the site of the nucleus, to enclose which the cell-body is thickened. (2) The intercellular substance is minimal in amount ; clear and homogeneous in character. (3) The cells are arranged, edge to edge, in a single layer. The wavy or denticulate edges of neighboring cells fit into each other, being separated by a mere line of the intercellular substance which in this tissue has received the name of " cement-substance " (Fig. 23). Endothelium forms a thin membranous tissue composed almost exclusively of cells. It occurs in its most isolated form in the cap- illary bloodvessels, the walls of which are simply tubes of endo- thelium, supported externally by the surrounding tissues and fluids and internally by the enclosed blood. It also covers the tissues surrounding the serous cavities of the body, where it serves both as a lining to the cavities and a smooth covering to the organs, dimin- ishing the friction resulting from their movements against each other. It does not occur in any situation where it would be exposed directly to the external world. The cells of endothelium vary somewhat in size and shape. They may be polygonal, diamond, or stellate in form, and during life are soft and extensible so that their sizes may be modified by stretching or tension in one or more directions. The cell-bodies, or cytoplasm, are usually clear and apparently structureless or only slightly granu- lar, but occasionally some of the cells are smaller and more granular than the majority. This is especially marked in the cells surround- ing minute apertures that are found here and there in the endo- 1 The term "epithelial" is used here in its most inclusive sense to designate those tissues which cover surfaces, whether those surfaces are exposed to the outer world, as, for example, the skin and the mucous membranes, or are wholly enclosed, as are the inner surfaces of the bloodvessels, lymphatics, and serous surfaces. 45 46 NORMAL HISTOLOGY. thelial lining of the serous cavities (Fig. 24). These openings are called stomata and furnish a direct communication between the se- rous cavities and the lymphatic spaces in the tissues surrounding them. These openings virtually convert the serous cavities into enormous lymph-spaces forming a part of the general lymphatic system. Fig. 23. Mesentery of frog treated with silver nitrate. The mesentery is covered on both surfaces with a layer of endothelium. Between these is areolar connective tissue containing bloodvessels, lymphatics, and nerves. In this figure only the two endothelial layers and a capillary bloodvessel are represented: a, nucleus of endothelial cell belonging to upper- most layer ; b, nucleus of cell belonging to deep layer forming the lower surface of the specimen; c, intercellular cement between cells of upper layer of endothelium ; d, d, nuclei of endothelial cells, forming a capillary bloodvessel, seen in profile. The bodies of these cells are not reproduced in the figure. The cement in the deep layer of endothe- lium is represented by finer lines to distinguish it from that belonging to the upper layer. The edges of contiguous endothelial cells are not everywhere in equally close approximation to each other (Fig. 2o). The occasional points where they are more widely separated than usual are occu- pied either by an increased amount of the cement-substance, or pro- cesses from cells in the underlying tissues are here intercalated between the endothelial cells, reaching the surface of the serous membrane. In either case these points of separation of the endo- thelial cells are not openings through the tissue, though, as we shall see in a subsequent chapter, they are spots where the tissue is rela- THE EPITHELIAL TISSUES. 47 tively more pervious than elsewhere. They are called pseudostomata, to distinguish them from the stomata already mentioned. Fig. 24. Endothelium on a serous surface of the frog. (Klein.) a, stoma bounded by endothelial cells "with granular cytoplasm ; 6, pseudostoma. The nuclei of the cells are not represented. The intercellular substance in endothelium is so small in amount and so homogeneous and transparent that it escapes observation Fig. 25. Endothelial lining of a small vein treated with silver nitrate ; dog. (Engelmann.) The fig- ure represents a tube formed of endothelium the cells of which vary in size and shape. The whole wall of a capillary has essentially the same structure as this venous lining, but its calibre is smaller. The upper branch in this figure may represent a capillary opening into the vein, a, u, pseudostomata occupied by cement-substance. under the microscope unless special means are employed for its dem- onstration. The simplest of these consists in treating the fresh -IS NORMAL HISTOLOGY. tissue with a 1 per cent, solution of nitrate of silver for a few mo- ments, washing with distilled water, and then exposing it to the rays of the sun. During this treatment the intercellular substance enters into combination with the silver. Upon exposure to strong light this compound is destroyed, leaving an insoluble black precipi- tate of silver oxide. When the specimen is examined under the microscope, the site of the cement-substance is marked by the presence of this precipitate. Endothelium so treated shows a net- work of fine dark lines, the meshes of which are occupied bv the cells of the tissue. When no such method has been employed to render the intercellular substance conspicuous, the outlines of the cells cannot be distinguished, and the tissue appears as a continuous, nearly homogeneous membrane containing nuclei at more or less regular intervals. When seen in profile or vertical section, endo- thelium appears as a delicate line, expanded at intervals to enclose a nucleus (Fig. 2f>). The nuclei of the endothelial cells are round or Diagram of vertical section through a serous membrane : a, nucleus of endothelial cell : 6, body of cell; c, line of junction between two cells occupied by cement-substance ; d, pro- cess of connective-tissue cell occupying a portion of the intercellular space between two endothelial cells, one variety of piemlastoma: r, areolar tissue with fusiform and stel- late cells. The vessels and nerves in the areolar tissue have been omitted. oval, and each cell usually possesses but a single nucleus situated near its centre, but occasionally cells with two nuclei are observed. Functionally, endothelium appears to play only a passive rule in most situations in which it is found. It furnishes a smooth cover- ing for those internal surfaces of the body which are exposed to friction, as, for example, in the serous cavities and the inner sur- faces of the vascular systems. In the capillary bloodvessels and lymphatics endothelium forms the entire wall of the vessels, and its thinness permits the passage of fluids through those walls. The fact that the lymph in different parts of the body varies somewhat THE EPITHELIAL TISSUES. 49 in composition has led to the inference that the endothelium of the capillary walls exercises an active function in determining what shall pass through it ; that the lymph is a sort of endothelial secre- tion. It is difficult, however, to reconcile this view with the fact that the endothelial cells are so poor in cytoplasm. Endothelium is developed from the mesoderm. II. EPITHELIUM. General Characters. — (1) The cells are nearly always large and rich in granular cytoplasm. They contain distinct round or oval, vesicular nuclei, of which there is usually only one in each cell. (2) The intercellular substance is very small in amount and is clear and homogeneous. (3) The arrangement of the cells and their size and shape all vary greatly, giving rise to a number of varieties of epithelium, which are classified according to the shape and arrange- ment of the cells. In pavement-epithelium the cells are thin and arranged in a single layer, not unlike endothelium. In cubical epithelium the cells are thicker and also usually arranged in but a single layer. In columnar epithelium the cells are prismatic in form and rest with their bases upon the surface of the tissues beneath. They are usually separated at their bases by pyramidal cells, so that the layer of epithelium cannot be said to consist strictly of but one layer of cells, and in some situations there are several distinct layers. In stratified epithelium the cells are superimposed upon each other to form a layer of cells, the thickness of which is several times the diameter of a single cell. The cells of the variety of epi- thelium called ciliated epithelium differ from those of the other varieties in possessing delicate, hair-like processes which project from the free surface of the tissue. Epithelium resembles endothelium in being composed almost exclusively of cells separated by a minimal amount of intercellular substance. Like endothelium, it is nearly always found covering other tissues and having one free surface. The two tissues differ greatly in the character of their cells, with one notable exception. This exception is found in the epithelial lining of the pulmonary alveoli, where the pavement-epithelium contains cells that closely resemble those of endothelium. These cells are, however, directly exposed to the inspired air, while endothelium is only found in situa- tions where it is protected from all contact with the external world. 1. Cubical Epithelium. — The cells of this variety of epithelium 4 50 NORMA L 1IISTOL 00 Y. are approximately of the same diameter in all directions. They may be almost strictly cubical or spherical, but are usually polyhed- ral as the result of mutual compression, their contiguous surfaces being flattened. They are usually disposed in a single layer upon a surface furnished by the underlying tissues, as, for example, in tubular or racemose glands, but they may be aggregated to form a solid mass of cells filling a sac, as in the sebaceous glands of the skin, or in strands or columns, variously disposed, as in the liver and suprarenal bodies. It is this form of epithelium that is chiefly concerned in perform- ing the functions of secretion, and, for this reason, it is frequently designated as " glandular epithelium." The appearance of the individual cells varies considerably accord- ing to the functions that they perform and the stage of functional activity which obtained at the time cellular changes were arrested when the particular specimen was prepared for study. It will suf- fice for present purposes of description to call attention to the fact that the cytoplasm is usually highly granular, partly because of its own structure, partly because many of the substances elabo- rated and stored within the cells as the result of their functions appear in th e form of granules (metaplasm). The nature of these granules varies. They may lie albuminoid, zymogenic granules, or minute drops of fatty substances, which may coalesce to form dis- tinct oily globules, or they may consist of carbohydrates, c. g., glv- cogen. The granular condition of the cytoplasm may be so marked Fig. 27. Fig. 2S. Fig. 29. ;& t:~ Cubical epithelium. Fig. 27.— Six cells from the sublingual gland of a man who was executed. (Sehiefferdeckcr.) Fig. 28.— Three isolated cells from the gastric tubules of the dog and cat. (Trinkler.l Fig. 2!i.— Cell with highly granular cytoplasm, the result of stored metaplasm, chiefly gly- cogen. (Barfurth.) as to render the detection of the nucleus difficult in unstained speci- mens (Figs. 27, 28, and 29). In this form of epithelium the presence of two nuclei in a single cell is more frequent than in the other varieties. THE EPITHELIAL TISSUES. 51 2. Pavement-epithelium. — This variety of epithelium consists of thin cells arranged edge to edge to form a single layer. With the exception of certain regions on the surfaces of the pulmonary alveoli, the cells are more cytoplasmic and granular than are those of endothelium which this tissue in other respects closely resembles. During fcetal life the smaller air-passages and alveoli of the lung are lined by a pavement-epithelium, the cells of which are nearly as thick as those of some varieties of cubical epithelium. When, however, the lung is expanded by the respiratory acts following birth, many of the cells lining the alveoli become greatly extended and flattened until their bodies are thin and membranous and their nuclei inconspicuous or even destroyed (Fig. 30). These greatly flattened epithelial cells are found covering those portions of the Fig. 30. Pavement-epithelium. Surface view of thelining of apulmonary alveolus; man. (Kolliker.) u, membranous cell without a nucleus ; b, nucleated granular cell ; c, cut surface of the vertical wall of the alveolus, the structure of which is not represented. alveolar walls in which the capillary bloodvessels are situated and permit a ready interchange of gases between the air in the alveolar cavities and the blood circulating in their walls. Many of the epithelial cells covering the tissues in the meshes between the capillaries retain the cytoplasmic and granular character possessed before birth and appear capable of multiplying and, perhaps, replacing such of the thinner cells as may be thrown off or destroyed. It will be evident, from the foregoing descriptions, that there 52 NORMA L HISTOL OOY. is no sharp structural line separating cubical from pavement-epithe- lium. Functionally, pavement-epithelium is a much less active tissue than the cubical variety. 3. Columnar Epithelium (Figs. 31, 32, 33).— The cells of this $1 V3/' Columnar epithelium. From tongue of pseudopus. (Seiler.) a, three cells with intact cyto- plasm, except the central one, which contains a vacuole ; o, three cells of which the dis- tal ends contain drops of fluid (vacuoles) or of metaplasm. form of epithelium are of a general columnar or prismatic shape and possess a single nucleus and a cytoplasm that is usually dis- tinctly granular. Thev are arranged with their long axes parallel to each other, so that their free ends form the. surface of the epithe- Fig. 32. Fig. 33. -b i ' "iafe^si JSiti i Columnar epithelium. Fig 32.— From small intestine of the mouse. (Paneth.) a, pyramidal reserve cell, nucleus not included in section ; b, " goblet " cell, enclosing a large drop of secretion. Fig. 33. — From small intestine of the mouse. (Paneth.) Columnar epithelial cells seen from above : 6, goblet-cell, the mucous contents darkened by the hardening process; s, s, highly granular cells which have recently discharged their secretion. lium, while their deeper ends either rest upon the tissues beneath the epithelium or upon other epithelial cells of different shape which form one or more layers between the columnar cells and the underlying tissues. When they rest directly upon the tissues beneath there are usually other epithelial cells of a pyramidal or oval shape which may be regarded as immature cells ready to take the place of such fully developed cells as may become detached or destroyed. The presence of these cells occasions a narrowing of THE EPITHELIAL TISSUES. 53 the deep ends of the columnar cells, so that they are not strictly prismatic in form. In cross-section, or when viewed in a direction parallel to their long axes, the cells have a polygonal form due to the lateral pressure they exert upon each other (Fig. 33). The nuclei of the columnar cells are oval, situated nearer the base of the cell than its superficial end with their long axes parallel to those of the cells themselves, and are vesicular in structure with a distinctly reticular arrangement of the chromatin filaments. Columnar epithelium is found chiefly upon the free surfaces of mucous membranes, but also occurs in some of the secreting glands. The minute structure of the cells varies somewhat in different situ- ations, but the consideration of these minutiae must be deferred until a description of the structure of the different organs is under- taken in a subsequent chapter. 4. Ciliated Epithelium (Figs. 34, 35, 36).— Ciliated epithelium Fig. 34. Fin. 3 /' Fig. 36. hb ok Ciliated epithelium. (Frenzel.) Fig. 34.— Cubical cells with long cilia (hb). The nuclei of the cells are obscured by the gran- ular cytoplasm. Fig. 35. — Columnar cells. The rodded margin, fs, corresponds to the cuticle in Fig. 37. Fig. 36. — Diagram illustrating variations in the structure of the ciliated ends of cells. The rodded portion, ok to uk, corresponds to the cuticle of other varieties of epithelium, though the latter do not possess the knobbed ends of the rods represented in this figure ; hb, cilia. is merely a variety of either columnar or cubical epithelium in which the free ends of the cells are beset with delicate hair-like processes, which execute lashing movements in some one direction. It is found lining the trachea and bronchi, the cilia here serving to propel toward the larynx such particles of dust as are brought into the respiratory passages by the currents of air during respiration. Ciliated epithelium also occurs on the lining membranes of the nose 54 NORMAL HISTOLOGY. and the adjoining bony cavities, the mucous membrane of the uterus and the Fallopian tubes, the vasa efferentia of the testis and a part of the epididvmus, the ventricles of the brain (except the fifth), the central canal of the spinal cord, and the ducts of some glands. The possession of cilia, which are very motile organs, presents a marked departure in specialization from the usual metabolic func- tions of epithelium. Ciliated epithelium rarely exercises a secretory function, its stock of energy being utilized to produce motion instead of chemical change. But there are secreting varieties of epithelium possessing a " cuticle " which appears to be morphologically anal- ogous to the cilia, but in which the fibrils are less highly developed, probably not motile, and, therefore, functionally not the equiva- Cuticularized epithelium, intestine of drier, (Paneth.) Rodded cuticle of the free ends of columnar cells. In most specimens of ciliated epithelium from human tissues, where no special care has been taken to preserve the cilia, the ciliated border presents the appear- ances shown in Fig. 37. lents of cilia. This cuticle is highly developed in the cells cover- ing the mucous membrane of the intestine (Fig. 37). 5. Stratified Epithelium. — In the varieties of epithelium hitherto considered the cells are, in the main, disposed upon some surface in a single layer, some, at least, of the cells usually extending from the bottom of the layer to its surface. Stratified epithelium is distinguished from these by being of greater depth and consisting of several layers of cells. The epithe- lium lining the cheek or the oesophagus may be taken as a typical example of this variety. The most deeply situated cells are small and nearly filled by the round or oval nucleus. They undergo frequent division, and as they multiply some of them are crowded toward the surface. For a time these increase in size through a growth of their cytoplasm. But as they are pushed nearer to the surface and farther from the sources of nutrition in the vascular tissues underlying the epithe- lium, they become flattened and their bodies lose their cytoplasmic character, being converted into a dry, horny substance, keratin. THE EPITHELIAL TISSUES. 55 Upon the free surface they are reduced to thin scales, closely adhering to each other and their subjacent neighbors, but entirely devoid of both cytoplasm and nucleus (Fig. 38). Stratified epithelium is found upon surfaces exposed to friction, which it serves to protect against mechanical injury, and, in some Fig. 38. Stratified epithelium, cesophagus of the rabbit : a, karyokinetic figure in a cell of the deep layer, demonstrating the fact that the cells multiply in this region; 6, larger flattened cell nearer the surface ; c, horny layer made up of cells that hare undergone keratoid degeneration ; d, underlying fibrous tissue. In one place, near the centre of the figure, six blood-corpuscles reveal the presence of a small vessel ; e, tangential section of a small fibrous papilla extending into the epithelium and surrounded by young epithelial cells. cases, against desiccation. It forms the epidermis of the skin, and lines the mouth, cesophagus, rectum, and vagina. In these situ- ations the scaly or squamous cells of the surface are constantly being removed by the attrition to which they are exposed, but are as constantly replaced by fresh cells from the deeper layers of the epithelium. Pressure and moderate friction stimulate the multi- plication of the cells in the deepest layers of the tissue, so that parts, e. g. of the skin which are especially subjected to such influ- ences acquire a thicker epidermis (callus). Where the stratified epithelium consists of many layers of cells, as is the case, for instance, upon the skin, there is a provision for the nourishment of the growing cells which are somewhat removed from the vascularized subjacent tissues. The cells of the deeper layers are somewhat separated from each other, leaving a space between them through which nutrient fluids can circulate. Across this space numerous minute projections or " prickles," springing from neighboring cells, join each other, forming connecting bridges between the cells. When isolated, such cells appear covered with these small spicules (" prickle-cells "), and their presence probably 56 NORMAL HISTOLOGY. increases the tenacity with which the cell-remains adhere to each other when they become hardened and toughened on the surface of the epithelial layer (Fig. 39). These delicate bridges connecting neighboring cells are not pecu- liar to stratified epithelium, though they are more conspicuous in that tissue than elsewhere. They have been observed between the cells of the columnar epithelium of the intestinal mucous mem- brane, and also between the cells of other elementary tissues ; c. g., smooth muscular tissue. 6. Transitional Epithelium (Figs. 40 and 41).— This variety re- sembles stratified epithelium in forming layers several cells in thick- Fig. 39. Prickle cells from human stratified epithelium. (Rabl.) Four cells with delicate processes unit- ing across an intervening space are represented. The lower right-hand cell is just below the upper surface of the section, so that its surface is seen. This is covered with minute spots, which are end views of the prickles directed toward the observer. The nucleus of this cell is not in sharp focus, a fact indicated by the fainter outline in the figure. ness, but differs in the character of its superficial cells. These do not undergo the horny change peculiar to stratified epithelium, but con- tinue to increase in size, forming a covering of very large cells lying upon those beneath. Under these largest superficial cells are piri- form cells lying with their larger, rounded ends next to the topmost layer, while their deeper and more attenuated ends lie between the oval or round cells that form the one or two deepest layers of the epithelium and rest upon the underlying tissues. Transitional epithelium is found lining the renal pelves, ureters, and bladder. Its structure permits of a considerable stretching of the tissues beneath without rupture of the epithelial layer over them, the cells of which become flattened to cover the increased surface, to return to their first condition when the viscus which they line is emptied. This is notably the case in the bladder, the epi- THE EPITHELIAL TISSUES. 57 thelial lining of which may be taken as a type of this variety of tissue. The functional activities of epithelium are in marked contrast to the comparatively inert character of endothelium. The cytoplasmic Fig. 40. Transitional epithelium from bladder of the mouse. (Dogiel. ) 1, 2, S, and 4 indicate the layers of cells, not everywhere equally well defined, a, hyaloplasmio surface, and, b, cyto- plasmic body of large superficial cell ; c, leucocyte— i. e., white blood-corpuscle that has wandered into the epithelium by virtue of its amoeboid movements ; d, karyokinetic figure in a, cell belonging to the deepest layer. Beneath this layer is the fibrous tissue, which is covered by the epithelium and forms a part of the wall of the bladder. The superficial cell, which is fully represented, contains two nuclei, a not very infrequent occurrence in these cells. nature of the epithelial cell, when contrasted with the poverty in cytoplasm of the cell in endothelium, would lead us to expect this difference in the cellular activities of the two tissues. At the begin- ning of this chapter a sketch of the manifold functions of epithe- Fig. 41. Transitional epithelium. Isolated cells from the bladder of the frog. (List.) lium was given. It is a fair general statement of its usefulness to say that epithelium is chiefly concerned in bringing about chemical changes in substances brought to it. Sometimes these substances are elaborated into fresh cell-constituents, and the activity of the 58 NORMAL HISTOLOGY. tissue is displayed chiefly in an active multiplication and growth of its cells. This is especially true in the stratified variety, where pro- tection is provided by a constantly renewed supply of cells. In other cases the substances received by the cells are elaborated into definite compounds destined to form the essential constituents of a secretion. This secretory function of epithelium is an extremely important one, and for its performance that tissue is usually ar- ranged in a special structure or organ, called a gland. A brief state- ment of the general characters and classification of these organs may here appropriately find a place. Secreting Glands. — The simplest type of secreting structure con- sists of a surface covered with a layer of epithelium, the cells of which are endowed with the power of elaborating a secretion and discharg- ing it upon their free surfaces (Fig. 32, b). The tissues supporting the epithelium belong to the connective tissues, and are fibrous in character and well provided with bloodvessels, lymphatics, and nerves. These bring to the epithelium the substances necessary for its nourishment and work, and place its activities under the control of the nervous system. Between the epithelium and the fibrous tissue supporting it there is frequently a thin membranous layer of tissue that often appears quite homogeneous, evidently belongs to the connective tissues, and has received the name of " basement-mem- brane." This appears to offer a smooth surface for the attachment of the epithelial cells, which receive their nourishing fluids through it. The epithelial surfaces of many of the mucous membranes are examples of the foregoing simple secreting structure. The secretory function is here of use as an adjunct to the protective function assigned to the epithelial covering, and the quantity of secretion is but slight under normal conditions. "Where the volume of secre- tion required is considerable some provision for an increase in the extent of secreting surface is necessary. This may be accomplished by an invagination of that surface, which then forms the lining of one or more tubes or sacs, into which the secretion furnished by the epithelial cells is discharged. Such an arrangement of the tissues constitutes a gland, and it is evident that these may be arranged into groups or classes according to whether the secreting surface forms a single tube or sac, or several such tubes or sacs, uniting to form a single gland. Thus, there may be simple or compound tubular glands, or simple or compound saccular glands. Whether the deeper portions of the gland have a tubular or saccular structure, the secre- THE EPITHELIAL TISSUES. 59 tion of the gland is discharged upon some free surface through a tubular outlet, called the duct. This is frequently lined with a non- secreting layer of epithelial cells differing in character from the actively secreting epithelium in the deeper portions of the glandular passages (Figs. 42-47). Fig. 42. Fig. 43. Fig. 44 Fig. 45. Diagrams representing various types of gland. Fig. 42.— Simple tubular gland : a, epithelium covering the surface on which the secretion is discharged ; b, mouth of gland ; e, epithelium lining the duct. This gradually passes into the secreting epithelium. Some simple tubular glands have no such distinction between the cells near the mouth and those nearer the fundus, but all the cells are of the secreting variety — i.e., exercise that function, e, secretory epithelium ; d, lumen. The sweat-glands are simple tubular glands which are coiled in their lower part to form a globular mass. Fig. 43. — Compound tubular gland : /, duct ; g, acinus. Fig. 44. — Racemose tubular gland : /,/,/, ducts ; g, g, acini. Fig. 45.— Simple saccular gland : /, duct ; g, acinus. 60 NORMAL HISTOLOGY. Fig. 46. Fro. 47. Diagrams representing various types of gland. Fig. 46. — Racemose saccular gland : /,/, ducts ; g, acinus. Fig. 47. — Compound tubular gland, with a marked distinction in the character of the epi- thelium in the duct and acini : c, duct epithelium ; /, duct ; d, lumen of the acinus ; e, secreting epithelium. This type of gland is common. This figure is introduced to show how difficult it might be to detect the lumen of the acinus in sections of such a gland. The lumen is of very small diameter (its size is exaggerated in this diagram) and runs such a tortuous course among the epithelial cells that even perfect cross-sections of the acinus might fail to reveal it if it happened at that point to run obliquely to the axis of the acinus. It would then appear merely as a small clear spot upon the granular cytoplasm of the cell that lay immediately beneath it. s, s', represent the way in which two such sections would contain portions of the acinus. The lumen in s' would be more easily detected than in s, because its general direction is more rectilinear and more nearly coincident with the line of vision. It is rarely possible to trace the connection between the ducts and other portions of a gland in sections, for the axes of these dif- ferent parts seldom lie in one plane. As a result of this circum- stance, sections of glands usually present a collection of round or oval sections of tubes or sacs, which are lined with a single layer of epithelial cells, surrounding a lumen. The cells in the deeper por- tions are usually granular and cubical ; those lining the ducts are generally more columnar in shape and less granular in character. The deeper portions are called the alveoli or acini of the gland, to dis- tinguish them from the ducts, and the character of the epithelium they contain differs according to the function of the gland. Sometimes the cells are so large that they nearly fill the acini, leaving a scarcely perceptible lumen. In other glands the cells are less voluminous and the lumen of each acinus is distinct. It occasionally happens, e.g., in the submaxillary glands, that the acini contain two sorts of cells which secrete different materials. Both kinds of cell may be present in the same acinus, or each kind may be confined to differ- ent acini. In studying sections of glands it must be borne in mind that the tangential section of an acinus would appear as a group of THE EPITHELIAL TISSUES. 61 cells surrounded by fibrous tissue, with no trace of a lumen among the epithelial cells (Fig. 48). Glands develop from surfaces which are covered by epithelium. Fig. 48. Section of gland from human lip. (Nadler.) a, duct, cut in slightly oblique direction (lumen oval), and probably near a branch, which would account for the apparent thickness of its epithelial lining in the lower half; b, cross-section of acinus secreting mucus ; c, tan- gential section of a similar acinus near its extremity and beyond the end of the lumen. Cross-sections of the cells at the fundus occupy the centre, d, cross-section of an acinus secreting a serous fluid, revealing a small lumen ; d', a similar acinus with a larger lumen, probably cut near its junction with a duct; e, acinus with crescentic group of cells with granular cytoplasm (e0, and other cells like those in b. The granular cells of small size are considered to be cells which have discharged their secretion and are accumulating material for a fresh supply. /, nearly axial longitudinal section of a portion of a mucous acinus ; g, tangential section of a serous acinus ; h, fibrous connective tissue between the acini ; i, capillary bloodvessel in the fibrous tissue. The cells of this epithelium multiply and penetrate into the under- lying tissues, forming little solid tongues or columns of cells (Fig. 181). If the gland is destined to be of the simple tubular variety, this col- umn of cells then becomes hollowed to form the lumen, the cells being 62 NORMAL HISTOLOGY. arranged in a single layer lining the tubule. If the gland is to be compound, the solid column of cells branches within the tissues, and then the lumina of the different portions are formed, the epithelium in the different parts becoming differentiated as specialization of function develops. The foregoing general description of the structure of secreting glands applies to those glands which have a purely secretory func- tion, discharging the products of their activities upon some free surface, such as the skin or a mucous membrane. There are other glandular organs which perform more complicated functions and the structure of which deviates from that of the simpler glands. Examples of these are furnished by the liver and kidney, the struct- ures of which must be deferred to a subsequent chapter. Other exceptions are exemplified in the thyroid body and other "duct- less" glands, which discharge no secretion into a viscus or upon a free surface, but which have an alveolar structure similar to an ordinary secreting gland. These alveoli do not communicate with ducts, which are wanting ; but whatever products they may eon- tribute to the whole organism are apparently discharged into the circulating fluids of the body by a process of absorption similar to that through which the glandular epithelium obtains its materials from those fluids, or by a direct discharge into the lymphatics. (See chapter on Ductless glands.) This process is indicated by the term " internal secretion," and is probably of commoner occurrence than is usually supposed. In fact, it but represents a special interpretation of the phenomena of interchange of material that is constantly going on between all the cells of the body and its circulating fluids. Epithelium is developed from the epiderm or hypoderm ; never from the mesoderm. In this respect, as well as in its functional rdle, it differs from endothelium. CHAPTER IV. THE CONNECTIVE TISSUES. The two varieties of elementary tissue that have just been con- sidered — namely, endothelium and epithelium — owe their qualities directly to the characters of the cells that enter into their composi- tion. The intercellular substances are insignificant in amount and subordinate in function. In marked contrast to these are the tissues composing the group known as the " connective tissues." Here the usefulness of the tissues depends upon the character of the intercellular substances which confer upon the tissues their physical properties. The activities of the cells entering into the composition of these tissues appear to be confined to the production of those important inter- cellular substances and the maintenance of their integrity. The cells may, therefore, be considered as of secondary importance in determining the immediate usefulness of the tissues, the first place being given to the intercellular substances. As was stated in the introductory chapter, these connective tissues are essentially passive — i. e., they are useful because of their physical characters rather than because of any ability to transform either matter or energy. Where the ability to accomplish those transformations is of importance the tissues are found to be essentially cellular in char- acter, as we have already seen to be the case in the epithelial tis- sues. The connective tissues may be divided into three main groups : the cartilages, bone, and the fibrous tissues. Each of these groups has certain general structural characters that distinguish it from the other elementary tissues, but within each group there are varieties which differ considerably in the detailed character of their intercellular substances and in the arrangement of these with re- spect to the cells. All the elementary tissues belonging to the connective-tissue group are developed from the mesoderm. 63 64 NORMAL HISTOLOGY. I. THE CARTILAGES. General Characters.— (1) The typical cell of cartilage is round or oval in shape, rich in cytoplasm, and possesses one (rarely two) nucleus of oval form and vesicular and reticulated structure. Within the cytoplasm there are frequently one or more clear spots, which are drops of homogeneous fluid, " vacuoles." The cells fre- quently depart somewhat from this type. Where the tissue is growing they are usually flattened on the sides turned toward their nearest neighbors. This is because they are the offspring of a cell that has recently divided, and are as yet separated by only a small amount of intercellular substance. Under these circumstances each cell is frequently surrounded by a thin layer of intercellular sub- stance, probably of relatively recent formation, which differs a little from that further from the cell and gives an appearance as though the cell were enclosed in a capsule. In older cartilage this appear- ance is no longer evident. Where cartilage is being replaced by Fig. 49. Hyaline cartilage. Section of human costal cartilage : a, nearly spherical cell containing two vacuoles ; b, recently formed intercellular substance (" matrix "), separating two cells that have been produced by the division of a single cell. There are several other examples of a similar grouping of cells, due to the same cause, in the figure. Between the cells is the hyaline, nearly structureless "matrix." bone, " ossification," the cells are arranged in columns, with only a small amount of intervening intercellular substance, and have a general cubical form. THE CONNECTIVE TISSUES. 65 (2) The intercellular substance is abundant in amount and has received the special designation " matrix." According to the char- acter of this matrix, the cartilages have been divided into three varieties : hyaline cartilage, fibro-cartilage, and elastic cartilage. In hyaline cartilage the matrix is clear and homogeneous and has the consistency of gristle. In fibro-cartilage it is traversed by or nearly wholly composed of delicate fibres similar to those of white fibrous tissue, which will be described presently. In elastic cartilage the matrix contains coarse, branching, and anastomosing fibres similar to those of elastic fibrous tissue (vide infra). (3) The arrangement of the cells and intercellular substances varies considerably. Sometimes the cells are pretty uniformly distributed throughout the intercellular substance. Sometimes they Fig. 50. Hyaline cartilage and perichondrium. Human costal cartilage. Same specimen as Fig. 49 . a, group of cells formed by division, but not yet separated by matrix ; 6, matrix ; c, cells with a comparatively slight amount of cytoplasm, marking the transition from cartilage to fibrous tissue ; d, perichondrium, composed of fibrous tissue (spindle-shaped cells with a fibrous intercellular substance). are arranged in groups of from two to four or even six cells. To- ward the surface of a piece of cartilage the cells are apt to be smaller than those nearer the centre, and are frequently flattened. Here, also, they often lose the characters that distinguish them in the body of the tissue, and more and more closely resemble the cells of the fibrous tissue surrounding the cartilage. This fibrous tissue is called the " perichondrium," and is usually not sharply defined from the cartilage itself, the matrix of the latter becoming more and more fibrous in character and the cells less distinctly like those 5 66 NORMAL HISTOLOGY. Fir, 51. ".--'. t - Hyaline cartilage. Section from human thyroid cartilage. (Wulters.) a, perichondrium ; b, peripheral zone of cartilage with flattened cells. In the deeper portions of the car- tilage the cells are larger, are arranged in groups, and are surrounded by recently formed matrix. The cells in the deepest portions of the cartilage are vacuolated, and about the groups of cells are fine granules of lime salts. In the matrix are numerous anastomosing lines, which are interpreted as fine canals, serv- ing to carry nourishment to the cells in the cartilage. tion some of the cells typical of cartilage until the distinction between the two tissues is lost. The peri- chondrium is wanting over the free surfaces of the articular cartilages. 1. Hyaline Cartilage (Figs. 49, 50, and 51). — Although under ordinary powers of the microscope and in specimens which have not been specially prepared the matrix of hyaline cartilage appears clear and almost, if not quite, homogeneous, closer study reveals the presence of a fine network within the clear intercellular sub- stance. This network is thought to be a system of minute channels through which the nutrient fluids permeate the tissue and reach its cells. It may be, however, that this reticulum is of fibrous character in which case the fibres might be more pervious than the surrounding matrix, and bear the same relations to the nutrition of the tissue as a system of minute channels. In sections stained with hematoxylin the matrix of hyaline cartilage often acquires a faint bluish tinge, the cytoplasm of the cells a deeper shade of the same color and the nuclear chromatin a verv dark blue. Hyaline cartilage forms the costal car- tilages, the thyroid cartilage, the ensiform process of the sternum, the cartilages of the trachea and bronchi, and the tem- porary cartilages which are subsequently replaced by bone. 2. Fibro-cartilage (Fig. 52).— This va- riety of cartilage is found in only a few situations : in the interarticular cartilages of joints, in some of the synchondroses, in one region in the heart, and in the intervertebral disks. In the latter situa- possess branching processes, extending for THE CONNECTIVE TISSUES. 67 some distance between the fibres of the intercellular substance, and giving the whole tissue a character closely resembling that of Fig. 52. Fibro-cartilage. Section from human intervertebral disk. (Schafer.) The cell to the left presents a branching process extending into the intercellular substance. white fibrous tissue. The cells are, however, more cytoplasmic than those of ordinary fibrous tissue. 3. Elastic Cartilage (Figs. 53 and 58).— This form of cartilage Fia. 53. Elastic cartilage. Section from cartilage of human external ear. (Bohm and Davidoff.) a, cartilage-cell ; 6, c, network of elastic fibres in the intercellular substance; 6, with large meshes : c, fine-meshed. Opposite a is a cell showing indications of a division of the cyptoplasm following division of the nucleus. is found in the epiglottis, the cornicula of the larynx, the ear, and the Eustachian tube. The coarseness of the anastomosing fibrous network of the matrix varies in different situations and in different 68 NORMAL HISTOLOGY. parts of the same piece of cartilage. The reticulum is usually more open and composed of larger fibres toward the centre of the tissue than at the periphery, where it becomes more delicate and finally blends with the fibrous intercellular substance of the peri- chondrium. It is evident, both from the structure of the cartilages and from the situations in which they are found, that they constitute elastic tissues suitable for diminishing the effects of mechanical shock. This is obviously the case in the joints, where both the hyaline and the fibrous varieties are found. Their elasticity and moderately firm consistency are also of obvious utility in the larynx and other air-passages and in the ear, nose, and synchondroses. II. BONE. General Characters.— (1) The cells of bone, called " bone-corpus- cles," have an oval vesicular nucleus, surrounded by a moderate amount of cytoplasm, which is prolonged into delicate branching processes that join those of neighboring cells. (2) The intercellular substance is composed of an intimate association of an organic substance and salts of the earthy metals. (3) The arrangement of these constituents is as follows: the organic basis of the inter- cellular substance is arranged in lamina?, which are closely applied to each other except at certain points where there arc cavities, called "lacuna?," giving lodgement to the bone-corpuscles. Joining these lacuna? with each other are minute channels in the intercellular substances, " canaliculi," which are occupied by the fine processes of the corpuscles. In the compact portions of the long bones, and wherever the osseous tissue is abundant, the lamina? are arranged concentrically around nutrient canals, the " Haversian canals," which traverse the bone, anastomosing with each other and contain- ing the nutrient bloodvessels of the tissue. In cancellated bone these Haversian canals are absent, and the thin plates of bone are made up of parallel lamina? of intercellular substance, between which are the lacuna 1 , connected with each other by canaliculi. The bone-corpuscles are nourished from the fluids circulating in the marrow, which occupies the large spaces of this spongy variety of bone. It is not possible in a single preparation to study even these gen- eral characters of bone. The earthy salts in the intercellular sub- THE CONNECTIVE TISSUES. 69 stance prevent the preparation of sections by means of the knife, and, unless they be removed, specimens of bone must be made by grinding. This can best be accomplished after the bone has been dried. But drying the bone destroys the corpuscles, which appear as little desiccated masses, devoid of structure, within the lacunae. Ground sections of bone can, therefore, give only an idea of the intercellular substance and the arrangement of the lacunae, canal- iculi, Haversian canals, etc. (Fig. 54). Sections may be cut if Pic. 54. ,*g!fi|fej^K' -jS.JrT.'fiSi'TM; JpiP -."-"^ **- - 1 . *&&Mmk * „ rZtr^&i ; M 5ga«£W|»t SotHsBI .- '•■■ '■' L WffBIMmk "\? > ^e^r ^&Se : 4fp r<\< '■* ■■• IF \ * ' * z& rngS^fc MHi £i_ d — II i-'-v'-il tar w ■dp" J WW>^^.^^'. Ground section of dried bone. Human femur, o, Haversian canal in cross-section ; a', Ha- versian canal occupied by debris ; a", anastomosing branch from a', in nearly longitud- inal section ; !>, lacuna belonging to the Haversian system, of which a' occupies the centre ; c, lacuna in excentric laminse of bone between the Haversian systems. The delicate lines connecting the lacunEe are the canaliculi. the bone be first decalcified — i. c, if the earthy salts be dissolved through the action of acids. This treatment not only removes the earthy constituents of the intercellular substance, rendering it soft and pliable, but causes the organic constituents to swell. The effect of this swelling upon the appearance of the bone is very marked. The fine canaliculi are closed and the lacunas diminished in size, so that the structure of the bone appears much simplified, being reduced to a nearly homogeneous mass of intercellular sub- stance in which there are spaces arranged in definite order and enclosing the somewhat compressed bone-corpuscles. The delicate processes of the latter are not discernible within the canaliculi, but blend with the swollen intercellular substance forming the walls of those minute channels. It is important that the student should learn to recognize these mutilated preparations of bone, since it is 70 NORMAL HISTOLOGY. in this form that the tissue will most frequently come under his observation (Fig. 55). Minute study of the structure of the intercellular substance of bone makes it appear that the organic basis is not homogeneous, but is composed of minute interlacing fibres, held together by Fig. 55. Section of decalcified bone, parallel to axis of human femur, a, longitudinal section of Haversian canal giving off transverse branch to the left ; b, tangential section of a trans- verse branch ; c, lacuna occupied by bone-corpuscle ; d, intercellular substance deprived of its earthy salts and so swollen that the canaliculi are obliterated. a cement or " ground " substance, containing the deposit of earthy salts. To these salts, which are chiefly phosphate and carbonate of calcium, the bone owes its hardness, while the fibres contribute toughness and elasticity to the tissue. The general arrangement of the fibres in the intercellular substance is in lamina?, which have a general parallel direction ; but there are occasional fibres of some size which pierce these laminse in a perpendicular direction and appear to bind them together, very much as a nail would hold a series of thin boards in place, " Sharpey's fibres." Bone occurs in two forms, the compact and the cancellated. These do not differ in the nature of the tissue itself, but merely in the arrangement of that tissue with respect to its sources of nourishment. AVhere the bone is massed in compact form, as in the shafts of the long bones, special means for supplying it with nourishment is provided by a scries of channels, the Haversian THE CONNECTIVE TISSUES. 71 canals, which contain the nutrient bloodvessels, and which anasto- mose with each other throughout the whole substance of the tissue. The nourishing lymph, derived from the blood, reaches the cells through the canaliculi and lacunae, which connect with each other to form a network of minute channels and spaces pervading the bone, and not only opening into the Haversian canals, but also upon the external and internal surfaces of the tissue. In the shafts of the long bones the Haversian canals lie for the most part parallel with the axis of the bone, with short transverse branches connecting them with each other. It is around these lon- gitudinal Haversian canals that the laminse of bone are arranged in concentric tubular layers. Each Haversian canal, with the lamina? surrounding it, is known as an Haversian system. Between these Haversian systems there are excentric laminse of bone, which do not conform to the concentric arrangement of the Haversian systems. In the spongy or cancellated variety of bone the thin plates of that tissue derive their nourishment from the lymph of the con- tiguous marrow filling the spaces between them, and there is no occasion for Haversian canals. The concentric arrangement of the laminae is, therefore, absent. Except where bounded by cartilage at the joints, the external surfaces of the bones are covered by a fibrous investment, the periosteum, in which the bloodvessels supplying the bone ramify and subdivide before sending their small twigs into the Haversian canals of the compact bone. The deep surface of the periosteum contains connective-tissue cells, " osteoblasts," capable of assuming the functions of bone-corpuscles and producing bone. These facts explain the importance of the periosteum for the nutrition and growth of bone. The tendons and ligaments attached to the bones merge with the periosteum, which has a similar fibrous struct- ure and serves to connect them firmly with the surface of the bone. The central cavities of the long bones and the spaces of cancel- lated bone are occupied by marrow, which may be of two kinds, the " red " or the " yellow." A description of the structure of marrow must be deferred until the other varieties of the connective tissues have been considered. In the embryo the parts which are destined to become bony first consist of some other variety of connective tissue, either cartilage 72 NORMAL HISTOLOGY. or fibrous tissue. This subsequently " ossifies," during which pro- cess it is not really converted into bone, but is gradually absorbed as that tissue develops and replaces it. III. THE FIBROUS TISSUES. General Characters. — This group of elementary tissues, which may be said to constitute the connective tissues par excellence, includes a number of varieties which are not very sharply defined, because of transitional modifications which bridge over the differ- ences between the more distinct types. It will, therefore, be best to describe these well-marked types of structure, and then to indi- cate the direction in which they are modified in particular cases so as to simulate in greater or less degree other typical varieties of the same group. (1) The cells of the fibrous tissues vary considerably in character, three more or less distinct forms being distinguishable. First, flat- tened, almost membranous cells with oval nuclei and nearly clear and homogeneous bodies, possibly identical with the cells that form endothelium ; second, granular cells, rich in cytoplasm and usually ovoid or cubical shape, though sometimes elongated ; third, elon- gated or fusiform cells, with oval nuclei surrounded by a moderate amount of cytoplasm which is frequently prolonged into processes of greater or less length and delicacy, and sometimes dividing into branches. These three sorts of cell are present in varying relative proportions in the different tissues belonging to this group. (2) The intercellular substance is composed of distinct fibres, asso- ciated with a homogeneous cement- or " ground-substance," lying between the fibres. The fibres are of two kinds : the " white," non-elastic, and the elastic or " yellow." The relative abundance of these and of the ground-substance associated with them, and also their arrangement, vary greatly in the different members of the group. (3) The arrangement of the constituents of the fibrous tissues in the different varieties is so diverse that a statement of the variations would amount to a description of the tissues themselves. The general characters already enumerated will serve to distinguish the whole group from all the other elementary tissues, and enable the student to recognize the fact that a given form of the tissue which he may have under observation belongs to this group. Before entering upon a description of the varieties of fibrous THE CONNECTIVE TISSUES. l! \>iS W- v < : •".;,'/.. .■'*.•--•.■'.!■' .•■. •'■>.'■' ■f.'.s : -rti ! '' -< V ^m£:<%& Striated muscular tissue. Fig. 78.— Diagrams of the structure of the contractile substance. (Rollet.) Q, sarcous elements, appearing dark in A, light in B; Zand J, sarcoplasm. The sarcoplasm also lies between the sarcous elements in Q, appearing as light bands in A and as dark lines in B. A is the appearance of the fibre when the focal plane is deep ; B, the appearance when the focal plane is superficial (see Fig. 76). The dots Z in A and -/in B are optical expressions of differences in the refraction of the sarcoplasm and sarcous elements, and do not repre- sent actual structures. A complete explanation of the way in which a microscopical im- age may contain apparent objects which have no actual existence cannot be entered into here. It is due to the fact that regularly alternating structures of different powers of re- fraction affect rays of light very much as they are affected by a fine grating, producing diffraction spectra. These spectra may interfere with each other, occasioning an alter- nation of light and dark bands or areas above the specimen. When the focal plane is changed the light areas become dark and the dark areas light, bnt sometimes with an alteration in their outline and relative sizes, as exemplified in the cuts. Fig. 79.— Cross-section of a muscle-fibre. (Rollut.) The fine reticulum, collected into larger masses at a few points in the midst of the contractile substance, is composed of sarco- plasm. The clear areas within this reticulum are the cross-sections of the sarcous ele- ments. These cross-sections are sometimes called "Cohnheim's areas." Immediately beneath the sarcolemma are cross-sections of two nuclei. nucleated, cylindrical cells. The body of these cells is almost ex- clusively composed of a very complex, contractile substance which pre- TISSUES OF SPECIAL FUNCTION. 93 sentsboth longitudinal and transverse striations, the latter much coarser and prominent than the former. It must suffice us to consider this con- tractile substance as made up of a number of prismatic bodies, " sarcous elements," which are arranged end to end to form col- umns, sarcostyles, extending parallel to each other, from one end of the cell to the other. The sarcous elements of all the sarcostyles lie in planes perpendicular to the long axis of the cell. It is, therefore, possible to separate the contractile substance into a number of fibre-like columns (sarcostyles, Fig. 65), made up of sar- cous elements attached at their ends, or to split it transversely into disks composed of sarcous elements lying side by side. Between the sarcous elements is a substance which has received the name " sarcoplasm." The contractile substance is enclosed in a thin, homogeneous mem- branous envelope, called the " sarcolemma." The nuclei of the cell lie immediately beneath the sarcolemma, between it and the contractile substance, and are surrounded by a small amount of unmodified cytoplasm. The muscle-fibres lie parallel to each other and to the general direction of the muscle which they compose, and are separated by loose areolar tissue, containing their vascular and nervous supplies. "When seen in cross-section they are circular or polygonal in form, and the cut surface of the contractile substance appears crowded with small polygonal areas, the sections of the sarcous elements, between which is the sarcoplasm. Where the nuclei are included in the section they appear somewhat flattened and lie at the edge of the contractile substance, where a thin zone of cytoplasm may sometimes be detected around them. The sarcolemma which lies outside of these constituents of the cell is so thin that it can rarely be distinctly seen. The muscle-fibres are in close contact at both ends with the dense fibrous tissue of the tendons attached to the muscle. CHAPTER VI. TISSUES OF SPECIAL FUNCTION {continued). II. THE NERVOUS TISSUES. The nervous tissues, like the muscles, are tissues of special func- tion, and are composed of highly specialized structures. Of these, only the ganglion-cells, the nerve-fibres, the neuroglia, and a few of Fig. 80. 1 *t ■ ' ., <■ ■ ■,,"„■■ Nerve- and neuroglia-cells from gray matter of spinal cord ; calf. (Lavdowsky.) The figure represents two isolated ganglion-cells, with branching protoplasmic processes, and each with a single axis-cylinder process, en. The axis-cylinder process of the lower cell gives off a branch a short distance from the cell. Between the ganglion-colls are those of the neuroglia. The protoplasmic processes of the nerve-cells subdivide into very delicate fibres, which lie among those of the neuroglia-cells. the modes of terminal distribution of the nerves will be considered here. 94 TISSUES OF SPECIAL FUNCTION. 95 1. Ganglion- or Nerve-cells (Figs. 80 and 81). — Nerve-cells vary greatly both in shape and size. They are rich in cytoplasm, and con- tain an unusually large nucleus, generally spherical in shape, within the reticulum of which there is nearly always at least one conspicu- Fig. 81. !:»■'..■ «:■ %. f §Li Section of unipolar nerve-cell from gray matter of spinal cord. (Flemming.) This figure shows the fibrillation of the axis-cylinder process and the cytoplasm of the cell, as well as the prominent chromophilic granules in the latter. ous nucleolus. The cell-bodies may be spherical, ovoid, polyhedral, or stellate in form, and are prolonged into one or more long pro- cesses. Some of these taper and branch repeatedly, the ultimate delicate fibrils terminating in free extremities lying in the inter- cellular substance, " dendritic processes." At least one of the processes emanating from each cell is coarser than these dendritic processes, and is prolonged into a nerve-fibre, forming the essen- tial constituent of that structure. This process is called the " axis-cylinder process." It does not branch as freely as the other processes, but may give off one or more lateral twigs near its origin. It is customary to divide the nerve-cells into unipolar, bipolar, and multipolar cells, according to the number of processes proceed- ing from them. The unipolar cells are connected by their single processes with nerve-fibres, and many of the bipolar cells, which have a fusiform shape, lie in the course of a fibre with which the two processes are continuous. In such cases one of the 96 NORMAL HISTOLOGY. processes is an axis-cylinder process. The multipolar cells nave one axis-cylinder process, the rest being of the dendritic type already mentioned, which are distinguished as "protoplasmic" processes. Nerve-cells are, as a rule, larger than the other cytoplasmic cells of the body, with the exception of the larger epithelial cells. Their cytoplasm is so finely granular that the cells look much more trans- parent than those of epithelium. With a high power the cytoplasm frequently exhibits fine striations, which are prolonged into the processes, giving them an appearance of longitudinal fibrillation. These appearances are due to the arrangement of the fibrils of spongioplasm. Considerable attention has of late been given to certain granules, which become evident in the cytoplasm when nerve-cells have been fixed in alcohol or in acid solutions. These granules have an affinity for dyes, " chromophilic granules," and usually occur in groups in the neighborhood of the nucleus. Their significance is not yet understood. The protoplasmic processes of the nerve-cells diminish in diam- eter as thev branch, and they also present occasional varicosities, which give them an irregular contour. They terminate either in fine-pointed extremities or in little, knobbed ends, and do not unite with those of neighboring cells, but form with them an intricate interlacement of delicate nervous twigs. The axis-cvlinder processes arise in conical extensions of the cell, and then become uniform in diameter and of a smooth contour without varicosities. When they branch the two divisions retain their size throughout their course until they enter into the forma- tion of some terminal structure. The average size of the nuclei of nerve-cells is greater than that of the other nuclei in the body, but they appear to contain less chromatin, and therefore stain less deeply and present a less distinct intranuclear reticulum. Nerve- or ganglion-cells are found in the gray matter of the central nervous system, in the ganglia, and sometimes in the course of nerves and in their peripheral terminations (Fig. 82). 2. Nerve-fibres. — There are two varieties of nerve-fibres : the white, or medullated, and the gray, or non-medullated. These differ both in their appearance when seen by the unaided eye and in their microscopical structure. (a) Medullated nerve-fibres consist of a central cylindrical struct- TISSUES OF SPECIAL FUNCTION. 97 ure running a continuous course from the cell giving it origin to the peripheral termination of the nerve, called the "axis-cylin- der " ; an external membranous envelope, the " neurilemma " ; and a semisolid material, the " myelin," " white substance of Schwann," or " medullary sheath," lying within the neurilemma and surround- ing the axis-cylinder. The axis-cylinder is a greatly elongated process (axis-cylinder process) springing from a nerve-cell. It is marked by longitudinal Fig. 82. Small ganglion in the tongue of a rabbit: a, a', ganglion-cells ; a', cell, with the beginning of its axis-cylinder process ; &, medullated nerve-fibre in cross-section ; c, fibrous tissue within the ganglion (part of this fibrous structure may be composed of non-medullated nerve-fibres) ; d, areolar tissue surrounding the ganglion and containing adipose tissue in the upper and lower parts of the figure. To the left is a striated muscle-fibre. The gan- glion is seen in cross-section, so that its connection with the nerves, in the course of which it lies, is not visible. striations, which appear to represent exceedingly delicate fibrils composing the axis-cylinder. These fibrils frequently separate at the distal extremity of the nerve and take part in the construction of the various forms of nerve-endings. A more minute study of the axis-cylinder leads to the inference that it is composed of spongioplasm, continuous with that of the body of the cell, and that the appearance of longitudinal striation is due to the elongated shape of the spongioplasmic meshwork and the greater thickness of its longitudinal threads, the transverse threads uniting them being much less conspicuous. 98 NORMAL HISTOLOGY. Fig. 83. The neurilemma, or external in- vestment of the nerve-fibre, called also the "primitive sheath," or ; sheath of Schwann, is a thin, Medullated nerve-fibre. (Key and Retzius.) A, node of Ran- vier; B, nucleus belonging to the neurilemma ; c, axis-cylin- . der; p, neurilemma, rendered r " " I' homogeneous membrane enclosing the medullary substance or myelin. At regular intervals, upon the in- ner surface of the neurilemma, and surrounded by a small amount of cytoplasm, are flattened, oval nu- clei, which appear to belong to the neurilemma. About midway be- tween these nuclei the nerve-fibre is constricted, forming the " nodes " of Ranvier. The neurilemma ap- ss through these nodes distinct by the retraction of without interruption, so that the the myelin of the medullary .. „ . -■ sheath, in the left-hand fig- neurilemma of one internode is ure the clefts of Lantermann con tinu0US with that of the adja- are shown as white lines in the darkmyelin. These figures are Cent internodes. At the nodes, taken from specimens treated t ,i ■,! • ,i „ ^„ • ... . „.,, ... „ . „ ant apparent! v within the neun- with osmie acid, which colors 11 the fatty constituent of the lemma, is a disk, perforated for the myelin a dark brown or black. . _ ., . passage ot the axis-cylinder, called the " constricting band " of Ranvier. It may be that this band is of the nature of a cement-substance, joining the neurilemma of neighboring internodes ; for the latter ap- pear to be developed from cells, probably of mesoblastic origin, which surround the nerve-fibres after their for- mation, becoming flattened to form membranous invest- ments of the nerve-fibre. If this view be correct, the neurilemma of each internode, with its single nucleus, is to be regarded as a single, specialized cell, derived from the surrounding connective tissues, and serving to protect the nerve-fibre. In perfect harmony with this conception of its nature are the facts that the nerves within the brain and spinal cord are destitute of neurilemma, and that when a nerve-fibre branches in its course the point of division is always at one of the nodes of Ranvier (Fig. 83). The medullary sheath, or myelin, is a soft material inter- TISSUES OF SPECIAL FUNCTION. 99 posed between the neurilemma and axis-cylinder. It is not a simple substance, but contains at least one constituent closely re- sembling fat or oil in its chemical nature ; also a substance chemi- cally allied to the keratin of horns and the superficial cells of the epidermis, called neurokeratin ; and a homogeneous, clear fluid. The way in which these constituents are combined is a matter of doubt, the apparent structure of the medullary sheath vaiying greatly when different modes of preparing the nerve for micro- scopical study have been employed. But the neurokeratin appears to exist as a delicate reticulum pervading the medullary substance. The medullary sheath appears to be interrupted at irregular inter- vals by oblique clefts, which surround the axis-cylinder like the flaring portion of a funnel. These " Lantermann's " clefts are occupied by a soft material, probably similar to that composing the constricting bands (Figs. 84 and 85). Fig. 84. v-1 f Fig. 85. / V-/ T Ax. C. Fig. 84.— Longitudinal view of portion of nerve-fibre from sciatic of dog. (Schiefferdecker.) S, neurilemma ; T, stained substance within the clefts of Lantermann. Fig. 85.— Cross-section from sciatic nerve of frog. (Bohm and Davidoff.) A, axis-cylinder, showing punctate sections of the nbrillEe ; B, medullary sheath stained with osmic acid ; a, b, apparent duplication of the medullary sheath, due to the presence of a Lantermann cleft; C, areolar tissue between the fibres. The medullary sheath is developed after the formation of the axis-cylinder, and is, at first, continuous along the course of the latter. Subsequently it becomes interrupted at the nodes of Ranvier by the constricting disk. It seems to be derived from 100 NORMA L IIISTOL G Y. Fig. 86. the axis-cylinder, and may, therefore, be regarded as a product of that greatly extended arm of the cytoplasm of the nerve-cell. The amount of medullary substance present in different nerves varies greatly. Sometimes it is so slight as to be hardly distin- guishable. In other cases its thickness considerably exceeds the diameter of the axis-cylinder. It is present within the spinal cord and brain, although not enclosed in neurilemma in those situations. At the peripheral ends of the nerves, on the contrary, it usually disappears before the neurilemma. The individual nerve-fibres are isolated only at their extremities. Throughout most of their course they are collected into bundles, forming the "nerves" of the body. Within these bundles the nerve- fibres are held together by fibrous tissue in the following manner : a delicate areolar tissue containing their vascular supply lies between the individual fibres. This fibrous tissue is called the " endoneurium." The nerve-fibres, thus held together, are aggre- gated into bundles, called "funiculi," which are surrounded by sheaths of still denser fibrous tissue, rich in lymphatic spaces, which are called the " perineurium." This perineurium on its inner surface becomes continuous with the endoneurium just de- scribed. The funiculi, enclosed by their perineurium, are, in turn, held together by an areolar sheath, which has received the name, "epineurium," and forms the outer covering of the nerve. The funiculi do not run a distinct course throughout the length of the nerve, but give off nerve-bundles, enclosed in peri- neurium, which join other funiculi ; the nerve-fibres themselves do not, however, anastomose with each other. (b) The gray, or non-medullated, nerve-fibres are, as their name implies, destitute of medullary substance. They consist of an axis- Nerve-fibres from the sympa- thetic system. (Key and Ret- zius.) All the fibres except that marked m are non-med- ullated. The fibre m has an incomplete medullary sheath. n, n, nuclei (if the neurilemma. These are surrounded by u small amount of cytoplasm, which is not clearly repre- sented in the figure. TISSUES OF SPECIAL FUNCTION. 101 cylinder, which at intervals appears to be nucleated. These nu- clei are presumably constituents of a membranous investment or neurilemma ; but the latter is difficult of demonstration because of its thinness and transparency, and its constant presence is not defi- nitely established (Fig. 86). Unlike the medullated variety, the gray nerve-fibres frequently give off branches, which join other fibres and constitute true anastomoses. Non-medullated fibres are most abundant in the sympathetic nervous system, but occur also in the nerves derived directly from the brain and spinal cord. 3. Neuroglia. — The nerve-cells and fibres of the central nervous system are surrounded and supported by a tissue which is derived from the epiderm, and is called the " neuroglia." It must be re- garded as a variety of elementary tissue having functions similar to the connective tissues, although its origin makes its relations to the epithelial tissues very close. Neuroglia consists of cells, the " glia-cells," which vary consider- Fig. si. Fig. 88. Glia-cells from the neuroglia of the human spinal cord. (Retzius.) Fig. 87.— Three cells from the anterior portion of the white matter : a, processes extending to the surface of the cord ; b, cell-body ; c, long, delicate process extending far into the white matter. Fig. 88.— Two cells from the deep portion of the white matter. ably in character, and an intercellular substance, which is for the most part soft and homogeneous, resembling in this respect the cement-substance found in epithelium, but which may, here and there, contain a few delicate fibres, possibly derived from the pro- cesses of some of the cells, or possibly of mesodermic origin, and, in consequence, belonging to the connective tissues. 102 NORMAL HISTOLOGY. The glia-cells possess delicate processes, which lie in the cement- or ground-substance and form a felt-like mass of interlacing fila- ments, but do not unite with each other. Two types of cell may be distinguished, but they are not sharply defined, because intermediate forms are met with. In the first type the cells have relatively large Fig. 89. Fig. 90. \ > v Glia-cells from the human spinal cord. (Retzius.) Fig. 89.— Cells from the substantia gelatinosa Solandi of the posterior horn. The cell to the right has a long process beset with fine, bluish branches. Fig. 90. — Four cells from the gray matter. Figs. 87-90 are taken from specimens stained by Golgi's method, which fails to reveal the internal structure of the cells, but is extremely well adapted to show the shapes of the cells and their extension into line processes. bodies, beset with a multitude of comparatively short, very fine, and frequently branching processes (Figs. 89 and 90). This type is most frequently met with in the gray matter. The second type of glia- cell is represented by cells with smaller bodies and longer and some- what coarser processes that branch much less freely (Figs. 87 and 88). They also often possess one particularly large and prominent proc- ess of greater length than the others. The small bodies of these cells serve to distinguish them from nerve-cells, with which they might otherwise be easily confounded. This type predominates in the white matter. Aside from the processes of the glia-cells already mentioned, the TISSUES OF SPECIAL FUNCTION. 103 Fig. 91. central nervous system contains fibrous prolongations of the epi- thelial cells of the ependyma and central canal of the spinal cord (Fig. 91). Fibrous constituents are also derived from the areolar tissue which extends into the organs of the central nervous system from their fibrous investments, the pia mater, in company with the vascular supply. The central nervous system, then, consists of a small amount of a ground-substance and a great number of cells, most of which possess numerous delicate fibrillar processes which interlace in all directions. Some of these cells are the function- ally active elements of the organs, the nerve-cells. Others belong to the sustentacular tissue, and are probably functionally passive, constituting the in- terstitlum. Both kinds of cell are developed from the epiderm, and are therefore genetically closely related to each other. 4. Nerve-endings. — Nerve-fibres terminate in two ways : first, in free ends lying among the elements of the tissues to which the nerve is distributed ; second, in terminal organs, containing not only nerve-filaments, but cells which are associated with them to form a special structure. The simplest mode of termination consists in a separation of the minute fibrillse Fig. 92. Ependyma and glia- cells from the spi- nal cord. (Retzius.) u, ependyma in the wall of the central canal ; 6, neuroglia- cell near the ante- rior fissure of the cord. Termination of nerves by free ends. (Retzius.) Nerve-endings among the ciliated columnar epithelium on the frog's tongue. Two goblet-cells, the whole bodies of which are colored black, are represented. The other cells are merely indicated. composing the axis-cylinders of the medullated fibres, or the chief bulk of the non-medullated fibres, into a number of delicate fila- 104 NORMAL HISTOLOGY. Fro. 93. Fro. 94. Termination of nerves by free ends. (Eetzius.) Fig. 93.— Two nerves terminating in the stratified epithelium covering the vocal cords of the cat. Fig. 94.— Nerve-fibres distributed among the cells lining the bladder of the rabbit : o, super- ficial layer of the transitional epithelium ; bg, fibrous tissue underlying the epithelium. merits, which branch and finally end among the tissue-elements to which the nerve is supplied. The filaments often present small vari- cosities, and sometimes end in slight enlargements corresponding to one of those swellings. In other cases the terminations are filiform (Figs. 92-94). A more complex mode of termination is that exemplified in the " motor-plates " of the striated muscle-fibre. Here the axis-cylinder TISSUES OF SPECIAL FUNCTION. 105 divides into coarse extensions, which form a network of broad vari- cose fibres, lying in a finely granular material containing two sorts of nuclei. This whole structure lies in close relations to the con- tractile substance of the muscle-fibre, but whether it is covered by the sarcolemma or not is a matter of doubt. The nuclei in the motor-plate are derived in part from the muscle-fibre, from the cytoplasm of which the granular material surrounding the nerve- Fig. 95. Motor-plate. Tail of a squirrel. (Galeotti and Levi.) a, two branches of axis-cylinder ter- minating in a plexus of varicose filaments ; b, muscle-nucleus ; c, nucleus derived from neurilemma. The finely granular substance surrounding these structures has been omitted. endings appears to be derived, in part from cells similar to those forming the neurilemma, which participate in the production of the motor-plate (Fig. 95). The nerves of sensation, like those supplying the striated muscles, end in bodies in which the nervous terminations are associated with cellular structures of peculiar form. Their consideration will be postponed until the structure of the nervous system is described. CHAPTEE VII. THE ORGANS. In the lowest order of animals, the protozoa, the single cell, which constitutes the whole individual, performs all the functions necessary to the life of the animal ; but in the higher multicellular animals, the metazoa, those functions are distributed among a num- ber of different but definite structures, called organs, each of which is composed of certain of the elementary tissues arranged according to a definite and characteristic plan peculiar to the organ. "Within each organ certain of the elementary tissues are charged with the immediate performance of the function assigned to that organ. These tissues are collectively termed the parenchyma of the organ. Thus, for example, the epithelium entering into the composition of the liver and doing the work peculiar to that organ, constitutes its parenchyma. The parenchyma of the heart is its muscular tissue, through the activity of which it is enabled to con- tract upon its contents. Functionally ancillary to its parenchyma, each organ possesses a variety of elementary tissues, some of which belong to the connec- tive-tissue group, which serve to hold the tissue-elements of the parenchyma in position, to bring to them the nutrient fluids neces- sary for their work, and to convey to them the nervous stimuli which excite and control their functional activities. These sub- sidiary tissues are collectively known as the interstitium of the organ. For example, the fibrous tissue and the elementary tissues forming the bloodvessels, lymphatics, and nerves of the liver, or of the heart, form the interstitia of those organs. Two sets of structures entering into the formation of the inter- stitia of the organs — namely, the nerves and the vessels, including those which convey blood and those through which the lymph cir- culates — have a similar general structure in all the organs, and are connected with each other throughout the body, forming " systems." These systems serve to bring the various parts of the body, so diverse in structure and function and yet so interdependent upon 106 THE ORGANS. 107 each other, into that intimate correlation that makes them subordi- nate parts of a single organism. Through the medium of the circulatory system the exchanges of material essential to the well-being of each organ and of the whole body are made possible, and through the nervous system the activ- ities of the different parts of the body are so regulated that they work in harmony with each other and respond to their collective needs. Because of their wide distribution throughout the body, we can hardly study any structures which are not in intimate relations with both vessels and nerves. It will, therefore, be well to consider the structure of the circulatory system before proceeding to a study of other organs. The study of the nervous system must, because of its complexity, be deferred. CHAPTER VIII. THE CIRCULATORY SYSTEM. The circulatory system is made up of organs which serve to pro- pel and convey to the various parts of the body the fluids through the medium of which those parts make the exchanges of material incident to their nutrition and functional activities. For some of these exchanges it appears necessary for the circu- lating fluids to come into the most intimate contact with the tissue- elements ; to penetrate the interstices of the tissues and bathe their structures. For mechanical reasons these fluids must circulate slowly and consume a considerable time in traversing a relatively short distance. Such a sluggish current could not avail for the transportation of oxygen from the lungs to the tissues, and we find that the circulatory system is divided into two closely related portions : the haematic circulation and the lymphatic circulation. The former is rapid, and the circulating fluid is the blood, the red corpuscles of which serve as carriers of oxygen. The latter is slow, and the circulating fluid, called " lymph," is derived from the liquid portion of the blood (" the plasma "). The blood is confined within a system of closed tubes, the bloodvessels ; but the lymph, when first produced by transudation through the walls of the bloodvessels, is not enclosed within vessels, but permeates the tissues or enters minute interstices between the tissue-elements surrounding the bloodvessels. Thence it gradually makes its way into larger spaces — lymph-spaces — which open into the thin-walled vessels constituting the radicles of the lymphatic vascular system. These smaller lymphatic vessels join each other to form larger tubes, which finally open into the venous portion of the haematic circulation, thus returning to the blood the lymph which has made its way through the tissues. The circulating fluids are kept in motion chiefly by the pumping action of the heart, which forces blood into the arteries, whence it passes through the capillaries into the veins, and thence back to the heart. During its passage through the smaller arteries, the capil- 108 THE CIRCULATORY SYSTEM. 109 laries, and the smaller veins, a part of the plasma of the blood, somewhat modified in composition, makes its way through the vas- cular walls, partly by osmosis, partly by a sort of filtration, and becomes the nutrient lymph of the tissues. The composition of this lymph varies a little in the different parts of the body, and this variation is attributed to some kind of activity, allied to secre- tion, on the part of the cells lining the vessels. The larger veins are provided with pocket-like valves, which collapse when the blood-current is toward the heart, but which fill and occlude the veins when, for any reason, the current is reversed. When, therefore, the muscles contiguous to the larger veins thicken during contraction and press upon the veins the effect is to urge the blood within them in the direction of the heart. This accessory mode of propulsion materially aids the heart, especially during active exercise, when the muscles are in need of an abundant supply of oxygen. The large lymphatic vessels are similarly provided with valves, and valves guard the orifices by which the lymphatic trunks open into the veins. But the chief reason for the flow of the lymph appears to be the continuous formation of fresh lymph, which drives the older fluid before it — the so-called vis a tergo. For convenient description we may divide the vascular organs into the heart, arteries, veins, capillaries, and lymphatics. 1. The heart is covered externally by a nearly complete invest- ment of serous membrane, the epicardium, which is a part of the wall of the pericardial serous cavity. Its free surface is covered with a layer of endothelium resting upon areolar fibrous tissue, and containing a variable amount of fat. The substance of the heart is made up of a series of interlacing and connected layers of cardiac muscular tissue, separated by layers of areolar tissue, which extends into the meshes of the muscle, form- ing the interstitial tissue of the heart. The fibres in the different layers of muscle run in different directions, so that sections of the Avail of the heart show the individual muscle-cells cut in various ways. The areolar tissue is more abundant and denser near the orifices of the heart, and at the bases of the valves merges into dense fibrous rings, which send extensions into the curtains of the valves, increasing their strength and giving them a firm connection with the substance of the organ. In the centre of the heart, between 110 NORMAL HISTOLOGY. the auriculo-ventricular orifices and the aortic orifice, this fibrous tissue is reinforced by a mass of fibro-cartilage. The cavities of the heart are lined by the endocardium, consisting of endothelium resting on areolar tissue. The deeper portions of the epi- and endocardium merge with the areolar tissue of the body of the heart. Smooth muscle-fibres are of occasional occurrence in the deeper layers of the endocardium. The auricles and the basal third of the ventricles contain ganglia, connected on the one hand with the nerves received by the heart from the cerebro-spinal and sympathetic systems, and on the other hand with a nervous plexus which penetrates the substance of the heart and gives off minute nervous fibrillse to the individual cells of the cardiac muscle. These fibrillse end in minute enlargements connected with the surfaces of the muscle-cells. Many of the gan- glia lie beneath the epicardium or in the areolar or adipose tissue situated in its deeper portions. The valves of the heart are composed of fibrous tissue, con- tinuous with that forming the rings around the orifices. Their surfaces are covered by extensions of the endocardium, except the outer surfaces of the pulmonary and aortic valves, which are cov- ered by extensions of the not dissimilar inner coats of the pul- monary artery or aorta. The fibrous substance of the valvular pockets of those two valves are further strengthened by tendinous strips of fibrous tissue at their lines of contact when the valves are closed. The curtains of the auriculo-ventricular valves are also reinforced by fibrous tissue derived from fan-like expansions of the ■chorda? tendinese. 2. The Arteries. — It will be best to consider first the structure of the smaller arteries, because the individual coats are less complex in these than in the larger arteries. The arterial wall consists of three coats : the intima, or internal (Coat ; the media ; and the adventitia, or external coat (Fig. 96). The intima consists of three more or less well-defined la vers. These are, from within outward : 1, a single layer of endothelium ; 2, a layer of delicate fibrous tissue containing branching cells ; 3, a layer of elastic fibrous tissue. The endothelial laver consists of cells, usually of a general diamond shape, with their long diago- nals parallel to the axis of the vessel they line. When the vessel .expands these cells broaden somewhat and appear very thin. When THE CIRCULATORY SYSTEM. Ill the vessel is contracted they are thicker and the portion containing the nucleus projects slightly into the lumen of the vessel. The subendothelial fibrous tissue forming the second layer of the intima is composed of very delicate fibrils, closely packed together, with a little cement between them, and enclosing irregular spaces in which the branching cells of the tissue lie. Elastic fibres, spring- Fig. 96. Brancb of splenic artery of a rabbit: a, internal endothelial surface of the intima; b, elastic lamina of the intima (fenestrated membrane, see Fig. 59) ; c, media composed of smooth muscular tissue encircling the vessel and therefore appearing in longitudinal section with elongated nuclei ; d, adventitia of fibrous tissue blending above and to the left with the surrounding areolar tissue ; e. adipose tissue, between the cells of which a few lines of red corpuscles reveal the presence of capillary bloodvessels; /, small nerve, containing both medullated and pale or non-medullated nerve-fibres. There are other similar sections of nerves in the figure. To the left of the artery the section is slightly torn, the adipose tissue being separated from the adventitia of the artery. A few red blood-corpuscles have been extravasated near the nerve at the upper left corner of the figure. There are also a few corpuscles within the lumen of the artery. ing from the external layer of the intima, may here and there, especially in the larger arteries, make their way into the subendo- thelial layer. The elastic lamina of the intima is formed by a network of anas- tomosing elastic fibres, having a general longitudinal disposition with respect to the axis of the vessel. The spaces left between the fibres of this network vary considerably in size. Where they are small and the fibres between them are correspondingly broad this layer has the appearance of a perforated membrane (the fenestrated mem- brane of Henle). Even where this membranous character of the elastic layer is well developed, elastic fibres are given off from its 112 NORMAL HISTOLOGY. surfaces and enter the subendothelial layer on the one side and the median coat of the artery on the other. The tunica media, or middle coat of the arteries, consists essen- tially of smooth muscular tissue, with the cells arranged trans- versely to the long axis of the vessels, so that by their contraction they serve to diminish the calibre of the arteries. The adventitia is an external sheath or layer of fibrous tissue Fig. 97. y"\i '^^L^'iSi <■ %/,• %m .... d »: e •■/ W~ -Z ?i IkJi >fc ~ ^-—^^v -JCv'- J . . 7 Portion of *> transverse section of a human lingual artery from an adult. (Griinstein.) o.intima; b, media; c, adventitia; d, endothelium; e f subendothelial stratum (delicate areolar tissue) ;/, tunica elastica interna (fenestrated membrane belonging to the intima) ; g, stratum subelasticuni containing clastic fibres (h) that pass from the fenestrated mem- brane into the media; i, concentric clastic fibres within the media; j, smooth muscular fibres of media with elongated nuclei; k, white fibrous tissue in media; ?, elastic fibres radiating from the media into the external elastic tunic ; m, stratum submusculare (are- olar fibrous tissue) ; n, tunica elastica externa ; o, stratum elasticum longitudinale (fibrous- tissue containing elastic fibres running parallel with the axis of the vessel) ; p, stratum elasticum concentricum (fibrous tissue containing elastic fibres encircling the vessel). The vasa vasorum supplying the tissues of the vascular wall are not represented. which merges with the areolar tissue of the parts surrounding the arteries and serves to support the latter without restricting the mobility necessary for their functional activity. THE CIRCULATORY SYSTEM. 113 In the larger arteries the muscle-fibres of the media are grouped in bundles, which are separated by white and elastic fibrous tissue (Fig. 97). The muscle-fibres themselves are less highly developed than in the smaller arteries, so that the vessels are less capable of contracting, but are more highly elastic, because of the greater abundance of elastic fibres. In these larger arteries the boundary between the media and the intima is less sharply defined than in the smaller arteries, the elastic tissues of the two coats being more or less continuous. In cross-sections of the smaller arteries this boundary is very clearly seen, the elastic lamina of the intima appearing as a prominent line of highly refracting material, which assumes a wavy course around the artery when the latter is in a contracted state. In such sections the nuclei of the endothelial layer of the intima appear as dots at the very surface of the intima. 3. The Capillaries (Fig. 25). — As the arteries divide into progres- sively smaller branches the walls of the latter and their individual coats become thinner. In the smallest arterioles the elastic tissue of the wall entirely disappears, and the muscular coat becomes so attenuated that it is represented by only a few transverse fibres partially encircling the vessel. These in turn disappear, and the branches of the vessel then consist of a single layer of endothelium continuous with that lining the intima of the larger vessels. These thinnest and smallest vessels are the capillaries. They form a net- work or plexus within the tissues, and finally discharge into the smallest veins the blood they have received from the arteries. It is chiefly through the walls of the capillaries that the transudation giving rise to the lymph takes place, but some transudation prob- ably also occurs through the walls of the smaller arteries and veins. 4. The veins closely resemble the arteries in the structure of their walls, but relative to the size of the vessel the wall of a vein is thinner than that of an artery. This is chiefly because the media is less highly developed. The elastic lamina of the intima is also thinner in veins than in arteries of the same diameter. The valves of the veins are transverse, semilunar, pocket-like folds of the intima, which are strengthened by bands of white fibrous tissue lying between the two layers of intima that form the surfaces of the valves. The valves usually occur in pairs, the edges of the two coming into contact with each other when the valvular pockets are filled by a reversal of the blood-current. 114 ' NORMAL HISTOLOGY. Behind each valve the wall of the vein bulges slightly. Single valves of similar structure not infrequently guard the orifices by which the smaller veins discharge into those of larger size. 5. The Lymphatics. — The lymph at first lies in the minute inter- stices of the tissues surrounding the bloodvessels from which it has transuded. In most parts of the body those tissues are varieties of fibrous connective tissue, and contain not only the small crevices between their tissue-elements, but larger spaces also, which have a more or less complete lining of flat endothelial cells, but permit the access of lymph to the intercellular interstices of neighboring tissues. The lymph finds its way into these " lymph-spaces," and thence into the lymphatic vessels. These begin either as a network of tubes with endothelial walls, or as vessels with blind ends, and have a structure similar to that of the blood-capillaries. They are larger, however, and are provided with valves. By their union larger vessels are formed, resembling large veins with very thin and transparent walls, consisting of intima, media, and adventitia. These finally unite into two main trunks, the thoracic duct and the right lymphatic trunk, which open into the subclavian veins. Valves are of much more frequent occurrence in the lymphatic vessels than in the veins, but their structure is the same. In its passage through the lymphatic circulatory system the lymph has occasionally to traverse masses of reticular tissue con- taining large numbers of lymphoid cells, called " lymph-glands." That portion of the lymphatic system which has its origin in the walls of the intestine not only receives the lymph which transudes through the bloodvessels supplying that organ, but takes up also a considerable part of the fluids absorbed from the contents of the in- testine during digestion. Mixed with this fluid is a variable amount of fat, in the form of minute globules. These globules give the con- tents of these lymphatics a milky appearance, and the vessels of this part of the lymphatic system have, therefore, received the name " lacteals." They do not differ essentially from the lymphatics in other parts of the body. Lymph-glands. — It is a misnomer to call these structures glands, for they produce no secretion. A better term is " lymph-nodes." The lymph-nodes are bodies interposed in the course of the lymphatic vessels through which the lymph-current passes. Their essential constituent is lymphadenoid tissue. Each node has a spherical, ovoid, or reniform shape, with a de- THE CIRCULATORY SYSTEM. 115 pression at one point, called the " hilus." It is invested by a fibrous capsule, which is of areolar character externally, where it connects the node with surrounding structures, but is denser, and frequently reinforced by a few smooth muscular fibres internally. Extensions from this capsule penetrate into the substance of the node, forming " trabeculse," which support the structures making up the body of the node. The lymphadenoid tissue occurs in two forms : first, as spherical masses, " follicles," lying toward the periphery of the node, except at the hilus, and constituting the " cortex " (Fig. 98) ; second, iu the Fig. 98. ''-mm' ■■•■ o^W'^M? Single lymph-follicle from a mesenteric node of the ox. (Flemming.) lb, wide-meshed lymphatic sinus at periphery of the follicle. Between this and the peripheral zone of the follicle z, and within the follicle, the reticulum of the sinus and that supporting the cells and vessels of the follicle are not represented. The cells are merely indicated by their nuclei, the cytoplasm being "omitted, z, peripheral zone of the follicle, marked by a close aggregation of small lymphoid cells ; p, more scattered cells outside of the peripheral zone and at the edge of the lymph-sinus. Within the zone z is the germinal centre of the follicle, in which numerous karyokinetic figures are.present, demonstrating the active proliferation of the cells in that region. Two such figures are also represented within the lymph-sinus at the upper left corner. 5, bloodvessels. form of anastomosing strands, which make a coarse meshwork of lymphadenoid tissue in the medullary portion of the node (Fig. 99). The trabeculse springing from the capsule penetrate the substance of the node between the follicles in the cortex, and then form a net- work of fibrous tissue lying in the meshes of the medullary lymph- adenoid tissue, after which they become continuous with the mass 116 NORMAL HISTOLOGY. of fibrous tissue at the hilus and, through it, with the capsule at that point. The lymphatic vessel connected with the node divides into a number of branches, the "afferent vessels," which penetrate the capsule at the periphery and open into a wide-meshed reticular tissue lying between the trabecule and the lymphadenoid tissue of the follicles and the medullary strands. This more open reticular tissue, through which the lymph circulates most freely, forms the Fig. 99. Portion of the medulla of a lymph-node. (Recklinghausen.) u, a, a, anastomosing columns of lymphadenoid tissue ; b, anastomosing extensions of the cortical trabecule : c, lymph- sinus ; d, capillary bloodvessels. The lymphoid cells in the sinus are not shown. "lymph-sinuses" of the node, and is less densely crowded with lymphoid cells than the reticular tissue of the follicles and medul- lary lymphoid tissue. The walls of these sinuses, which are turned toward the fibrous tissue of the trabecule and their extensions in the medulla, are lined with endothelium, and a somewhat similar, but probably much less complete, lining may partiallv separate the sinuses from the lymphadenoid tissue. However this may be, it is certain that lymphoid cells can freely pass from the lymphoid tissue into the sinuses, or in the reverse direction, and that there is a ready interchange of fluids between the two. From the sinuses the lymph passes into a single vessel, the " effe- rent vessel," through which it is conveyed from the node at the hilus. The arteries supplied to the lymph-node may be divided into two THE CIRCULATORY SYSTEM. 117 groups : first, small twigs which enter at the periphery and are dis- tributed in the capsule and fibrous tissues of the trabecular and the medulla; and, second, arteries which enter at the hilus, pass through the sinuses, and are distributed in the lymphadenoid tissue of the medulla and cortex. The veins follow the courses of the corre- sponding arteries. The nerve-supply is meagre, and consists of both medullated and non-medullated fibres. Their mode of termination is not known. In the centre of the follicles the reticular tissue is more open and the lymphoid cells less abundant than toward the periphery. Mitotic figures are of frequent occurrence in lymphoid cells in this region, and it is evidently a situation in which those cells actively multiply. Further toward the periphery the reticular tissue is closer and very densely packed with small lymphoid cells, to be- come more open again and freer of cells as it passes into the reticulum of the sinus (Fig. 100). This last reticu- . Fig. 100. WMS89?'-- . ?w mm, ) -': if V Fig. 100.— Portion of lymph-follicle from mesentery of ox. (Flemming.) z peripheral zone of small, closely aggregated lymphoid cells. To the right of these is a portion of the germinal centre of the follicle, with larger cells, many of which are dividing. Opposite lis a, cell executing amoehoid locomotion, p z, pigmented cell, which has taken upcolored granules from outside ; t k, dark chromophilic body, the nature of which has not been determined. Such bodies occasionally occur in lymph-nodes, but their origin and sig- nificance are unknown. Fig. 101.— Section of a small portion of the reticulum of the sinus in a human mesenteric node. (Saxer.) b, b, diagrammatic representation of a portion of the neighboring trabecula. lum becomes continuous with delicate fibres given off from the tissues of the capsule and trabecular (Fig. 101). The distribution 118 NORMAL HISTOLOGY. of the lymphoid cells gives the follicles a general concentric appear- ance. The lymph-follicles of the cortex not infrequently blend with each other, and the activity of the cellular reproduction in their centres varies considerably and is sometimes entirely wanting, when the concentric arrangement of the cells disappears. The structure of the lymph-nodes causes the lymph entering them to traverse a series of channels, the " sinuses," which, in the aggre- gate, are much larger than the combined lumina of the vessels sup- plying them. The velocity of its current is, therefore, greatly re- duced, and it remains for a considerable time subjected to the action of the lymphoid cells in and near the sinuses. Small particles which may have gained access to the lymph in its course through the tis- sues are arrested in the lymph-nodes, and are either consumed by phagocytes — i. rojections of the subserous fibrous tissue, which contain adipose tissue, appendices epiploicEe. 8. The rectum resembles the colon in its structure, except that the three muscular bands present in the latter are wanting. The mucous membrane as it passes into the anal canal loses its tubular glands, and subsequently becomes covered, not with columnar, but with stratified epithelium, continuous with the epidermis of the skin around the anus. 9. The pancreas (Fig. 122) has a structure similar to that of the salivary glands, but its lobules are separated and held in place by a rather more considerable amount of loose areolar tissue, in which there are occasional groups of cells of uncertain nature, but cer- tainly distinct from those lining the glandular acini. They are called the " interalveolar cell-islets," and may, perhaps, be of the nature of ductless glands (q. v.). • As the pancreas exercises its secretory function the granules within its cells move toward the lumina of the acini and successively disappear, the attached ends of the cells becoming clearer and the whole cell diminishing somewhat in size during the process. The nerves of the stomach and intestinal tract form two a:an- glionated plexuses, the plexus of Auerbach, which lies between the two layers of the muscular coat, and the plexus of Meissner, situ- THE DIGESTIVE ORGANS. 143 ated in the submucous coat. From these plexuses fibres are dis- tributed to the muscles and other structural elements. These fibres are of the non-medullated variety. The nerves of the pancreas are also non-medullated, possess a few ganglia within the organ, and are finally distributed among the epithelial cells. The Tonsils, Lymph-follicles, and Peyer's Patches. — These collec- tions of lymphadenoid tissue in the alimentary tract have special Fig. 122. Suction of human pancreas. (B6hm and Davidoff.) a, larger duct ; b, beginning of duct ; c,rl, acini with cells belonging to the corresponding duct-radicles in their centers ; e, acinus, cut just beyond the lumen; /, interalveolar cell-group (?) ; g, fibrous connective tissue, forming the interstitial tissue of the organ. interest to the physician as being points particularly liable to infec- tion. The solitary follicles of the stomach and of the small and large intestine, and the collections of such follicles forming the patches of Peyer, are the sites which are most vulnerable to invasion by pathogenic bacteria in the digestive tract, though they are probably protected to a considerable extent by the germicidal powers of the acid gastric juice. This is not always capable of guarding them from infection by the typhoid and tubercle bacilli, and in the diseases of the intestinal canal occasioned by those bac- teria the follicles and Peyer's patches are the seat of the earliest and most extensive ulcerations. The tonsils, which have the same general structure, are still more prone to infection of various kinds, 144 NORMAL HISTOLOGY. for they are more directly exposed to the action of bacteria that may gain access to the mouth. The reason for this vulnerability appears to lie in the close prox- imity of the lymphatics to the surface and their meagre protection by a thin layer of epithelium liable to abrasion or destruction. The solitary follicles of the intestine, for example, are covered with a single layer of columnar epithelium (Fig. 121). The lymphadenoid tissue of the tonsil, it is true, is protected by a layer of stratified epithelium ; but the surface of the tonsil is invag- inated to form the crypts of that organ, and within those crypts it Fig. 123. ,.K.f '■;■:■;. : ;& : ' '■'■''■ • •. Section through one of the crypts of the tonsil. (Stohr.) e, stratified epithelium of the gen- eral surface, continued into the crypt; /, follicles containing germinal foci. Between the follicles is a more diffusely arranged lymphadenoid tissue, s, material within the crypt, composed in part of lymphoid corpuscles that have wandered through the strati- fied epithelium. is possible for bacteria to multiply and produce such an accumula- tion of poisonous products as to destroy the integrity of the epithe- lium and so permit au invasion of the lymphadenoid tissue beneath. We therefore find the tonsils specially prone to such inflammatory THE DIGESTIVE ORGANS. Fir;. 124. 145 Section through the fundus of a crypt. (Benda and Guenther's Atlas.) a, stratified epithe- lium, desquamating at its surface ; b, deep portion of the lymphadenoid tissue, in which proliferation of lymphoid cells takes place as well as in the follicles represented in Fig. 123. processes as tonsillitis and diphtheritic inflammation (Figs. 123 and 124). 10 CHAPTER XI. THE LIVER. That portion of the liver which is exposed in the abdominal cavity is covered by a reflection of the peritoneum, closely attached to the organ, because its deeper side is continuous with the fibrous structures or interstitial tissue of the liver itself. This serous cover- ing is so thin that the substance of the liver can be readily seen through it. At the portal fissure, the serous coat having been reflected from it, the liver is covered with a loose areolar tissue in which the main trunks of all but one of the vessels connected with it are situated ; namely, the portal vein, hepatic artery, gall-duct, and lymphatics. These vessels enter the liver together at this place, and are closely associated with each other in all their ramifications, being supported throughout by areolar tissue, which is continuous with that at the portal fissure and with the interstitial tissue of the liver. These vessels, with their supporting fibrous investment, called Glisson's capsule, ramify in the liver in such a way as to resemble a tree with a multitude of branches and twigs, each composed of ■divisions of all the vessels named. The hepatic vein enters the liver at a different place, and also suffers a tree-like subdivision ; but its branches are surrounded by a very much smaller amount of fibrous tissue, which may be regarded as but a slightly reinforced portion of the interstitial tissue of the organ. Sections of the liver (l^ig. 12-1) will reveal portions of these tw r o trees, cut in various directions with respect to their axes. It will be observed that the twigs and larger branches of the trees are nowhere in close relations to each other, showing that the hepatie vein, in all its ramifications, is separated from the other vessels bv the parenchyma of the organ. If we select some part of a section which contains one of the smallest branches of the hepatie vein, and cut across its axis so that its lumen appears round, wo shall notice that at about equal distances from it there are sections of two, 14fi THE LIVER. \A1 three, or four twigs of the compound tree. In these the gall-duct can be identified by its distinct lining of columnar or cubical epi- thelium, and the hepatic artery distinguished from the portal vein by its relatively thick wall as compared with the size of its lumen. These vessels are collectively known as the interlobular vessel a. Between and around them is the areolar fibrous tissue, which forms a part of Glisson's capsule, and which is abundantly supplied with Fig. 125. Diagrammatic sketch of a section of liver : a, central vein (radicle of the hepatic vein) ; b, b, branches of the portal vein ; c, c, branches of the hepatic artery ; d, d, small bile-ducts ; e, lymphatic vessel; b, c, d, e are enclosed in areolar tissue, which is continuous with Glisson's capsule ; /, liver-cells ; g, line indicating the junction and blending] of two neighboring lobules. lymphatic spaces and vessels in the fibrous tissue. The lymphatics appear as clear spaces with smooth walls, some of them with dis- tinct endothelial linings, but almost devoid of any other wall. The parenchyma may be subdivided into portions which surround the smallest branches of the hepatic vein, and are bounded by imaginary lines connecting the groups of interlobular vessels. These subdivisions are called '' lobules " of the liver. In the human liver they blend at their peripheries, between the masses of connective tissue enclosing the interlobular vessel ; but in the liver of the pig these lobules are veritable subdivisions of the liver, and 148 NORMAL HISTOLOGY. are separated by septa of fibrous tissue, the interlobular vessels lying in the lines formed by the junction of three such septa. Connecting the branches of the portal vein with the hepatic vein is a plexus of capillaries, called the intralobular wx.sr/.s-, through which the blood passes from the portal vessels to the radicles of the hepatic vein and thence into the general circulation. These intra- lobular vessels also receive blood from the hepatic artery, the capillaries from which join them at a little distance from the periphery of the lobule. The radicles of the hepatic vein are called the central veins, from their situation in the axes of the lobules, which are conceived as having a somewhat cylindrical shape (Fig. 126). Fig. 126. Vessels and bile-ducts of a lobule of a rabbit's liver in transverse section. (Cadiat.) u, cen- tral vein ; b, b, interlobular veins (branches of the portal vein) ; c, interlobular bile-duet, receiving capillary bile-ducts from the lobule. Between a and b is the capillary plexus called the intralobular vessels. The biliary radicles are not represented throughout the figure, and the branches of the hepatic artery have been wholly omitted. Between the interlobular capillaries are rows of epithelial cells, which constitute the functional part of the liver, its parenchyma. They appear to touch the walls of the capillaries, but are, in reality, separated from them by a narrow lymph-space (Fig. 127). In the 'Villi LI vim. 149 human liver the epithelial cells of the parenchyma form a plexus lying in the meshes of the capillary network of the interlobular vessels. It requires an effort of the imagination to conceive of a third plexus within the lobule, but such a plexus exists, being formed of the radicles of the gall-duct. These are minute channels situated between contiguous epithelial cells, each of which is grooved upon its surface to form half of the tiny canal. The cells themselves have fine channels running from the bile-capillaries into their cyto- plasm and ending there in little rounded expansions. It is difficult to detect these bile-capillaries in ordinary sections of the liver, unless they have been previously injected through the main duct; but with a. high power their cross-sections may sometimes be clear] v seen, appearing as little round or oval spaces at the junction of two Fig. 128. ,ry- m •■V" *<*' 1 C:-D: # '•-i% Pig. 127.— Perivascular lymphatic of the human liver. (Disse.) c, capillary in longitudinal section; a, lymphatic space between the capillary and row of epithelial cells; b, wall of the lymphatic space, slightly separated from the liver-cells and drawn a little em- phatically; 1, liver-cells; cl, bile-capillaries in cross-section, with their intracellular ramifications. Fig. 128— Bile-capillaries between the liver-cells, with minute channels penetrating the cells and communicating with secretory vacuoles within the cytoplasm. Injected liver of the rabbit. (Pfeiffer.) epithelial cells, midway between the nearest capillary bloodvessels. Throughout their whole course they appear to be separated from the nearest bloodvessels by a distance approximately equal to half the diameter of one of the epithelial cells. It is this fact that makes it so difficult to frame a mental picture of their distribution in the lobule (Fig. V2S). The nerves supplying the liver ramify in extremely delicate, non- 150 NORMAL HISTOLOGY. medullated fibrils, which ramify throughout the substance of the liver and terminate in minute twigs among its epithelial cells. The epithelial cells of the liver have a cubical shape, the grooved and other surfaces that come in contact with neighboring cells being flat, while the remaining surfaces may be somewhat rounded. The cytoplasm is granular, and, except after a considerable period of starvation, more or less abundantly infiltrated with irregular gran- ules and masses of glycogen and globules of fat (Fig. 129). The Fig. 129. m ,*,. Portion of hepatic lobule of the rabbit; cells infiltrated with glycogen. (Barfurth.) The animal had been fed for twenty-four hours on wheat-bread, to promote the storage of gly- cogen within the liver-cells. The cells in close proximity to the central vein contain the largest amount of glycogen, which appears to fill the cytoplasm. Further from the central vein the cells contain less glycogen, which is most abundant in that portion of the cell turned toward the centre of the lobule. Fat-globules are most abundant in the cells at the periphery of the lobule. No fat-globules are represented in this figure. glycogen dissolves out of the cells during the ordinary processes of fixation and hardening preparatory to the preparation of sections, leaving spaces in the cytoplasm, which cause it to have a coarsely reticulated appearance in cases where the glycogen was abundant. This reticulation would render it impossible to distinguish the minute intracellular bile-passages. Each cell lias a round vesicular nucleus near its centre. In rare instances two nuclei may be found in a single cell. It will, perhaps, make the structure of the liver a little more comprehensible if it is stated that the liver of some of the lower animals is a tubular gland, the tubes of which are lined with a layer THE LIVER. 151 of epithelium. In the human liver this tubular structure is dis- guised by the facts that the tubules anastomose with each other, and that their lumina are very minute and bounded by only two cells when seen in cross-section. So inconspicuous are these lumina that a casual glance at a section of a liver would not reveal the fact that it was a glandular organ. The interstitial tissue of the liver consists of a few sparsely distributed fibres continuous with those of Glisson's capsule. The intricate structure of the liver prepares us for the fact that its function is an extremely complex one. It is a secreting gland, elaborating the bile and discharging it into the duodenum. But the bile has more than one purpose. It aids in the digestion and absorption of food, and it also contains excrementitious matters destined to leave the body through the alimentary tract. Even the secretory function of the liver, therefore, serves a double purpose : the supply of substances useful to the organism and the elimina- tion of products that would be detrimental if retained. But the function of the liver is not confined to the elaboration of the bile. It also acts as a reservoir for the storage of nourish- ment, which can be drawn upon as needed by the organism. This is the meaning of the glycogen and fat which have infiltrated the cells. The food-materials that are absorbed from the digestive tract pass into the system through two channels : the lymphatic and the portal circulations. The latter carries them to the liver, where some of the fat, probably after desaponification, is taken up by the epithelial cells, which also appropriate a portion of the sugar in the portal blood, transforming it into glycogen and holding it in that form until a relative deficiency of glucose in the blood reveals its need by the system. The blood comes into such close relations with the epithelial cells of the liver that an interchange of soluble substances between them appears to be about as easy a matter as the interchange of gases between the blood and the air in the lungs ; and, as in the latter case, this interchange is mutual : some matter passing from the blood to the liver-cells and some from the cells to the blood. In the lung there is a gaseous regeneration of the blood ; in the liver, a renovation as to certain of its soluble constituents. The Gall-bladder. — The bile is secreted continuously by the liver, for it is an excrement ; but it is discharged intermittently into the 152 NORMAL HISTOLOGY. alimentary tract, as required by the digestive processes. In the interval it is stored in the gall-bladder. The gall-bladder is lined with columnar epithelium, capable of secreting mucus. Beneath this is a layer of fibrous tissue, which becomes areolar and supports the chief bloodvessels and lymphatics. Beneath this is the wall of the organ, composed of interlacing bands of fibrous and smooth muscular tissues. The surface is invested by a portion of the peritoneum. The excretory bile-duct has a similar structure. CHAPTEE XII. THE URINARY ORGANS. The urine is secreted by the kidney, whence it passes succes- sively through the renal pelvis, ureter, bladder, and urethra into the outer world. 1. The kidney is made up of homologous parts or lobes, which are readily distinguished in early life by the superficial furrows marking their lines of junction. In later years these depressions on the surface of the kidney disappear. Each of the lobes corre- sponds to one of the papillae of the kidney and the pelvic calix that embraces it. In some of the lower animals — c. g., the rabbit — the kidney has but one papilla, so that the whole renal pelvis in those animals corresponds to a single calix in man. The kidney is a compound tubular gland of peculiar construc- tion, the tubules taking origin from little spherical bodies, called Malpighian bodies, instead of from simple blind extremities, and, after running a definite and somewhat complicated course, uniting successively with several others to form the excretory ducts, called the "collecting tubules," which open into the calices near the tips of the papillae. If a section of the organ be made through its convexity down to the pelvis, the papillae will be seen projecting into the calices of the pelvis, and it will be noticed that each papilla forms the apex of a pyramidal portion of tissue having a different tint and texture from the rest of the kidney. These pyramids form the " medulla " of the organ (Fig. 130). The bloodvessels supplying nearly all its substance enter the kidney near the bases of the pyramids, having approached the organ through the fat that lies around the calices. Within the kidney they break up into branches that run along the base of each pyramid in that portion of the organ which is called the "boundary zone." Between that zone and the convex surface of the kidney the tissue is known as the "cortex." The arrangement of the renal tubules, which make up the chief 153 154 NORMAL HISTOLOGY. bulk of the kidney, can be most easily understood if they are traced back from their openings at the apex of the pyramid to their Fig. 130. Lobe Lobule Re >ial Pelvis Diagrammatic sketch of a section of the kidney: u, columnar epithelium covering the external surface of the pyramid and continuous on the one hand with the columnar epithelium lining the collecting tubules within the pyramid, and on the other hand with the transitional epithelium lining the calices and renal pelvis. This transitional epi- thelium is indicated at 6. It rests upon the fibrous tissue of the calices and pelvis, which becomes continuous with the fibrous capsule of the kidney at the junction of the calices with that organ. Outside of this capsule is the perinephric fat, indicated in the figure between the calices. The vessels approach the kidney through this fat, entering its sub- stance near the bases of the pyramids and forming the vascular arcades (e, arterial arcade). From these arcades the interlobular vessels proceed, between the medullary rays and in the labyrinth, toward the convex surface of the kidney, d, interlobular artery, giving off branches, the afferent vessels, to the Malpighian bodies. The extensions of the cor- tical substance between the pyramids, c, are known as the columns of Bertini. During infancy the lobes of the kidney are marked by sulci upon the surface of the organ. With the growth of the organ these lobes blend with each other, and the sulci between them become indistinct or are wholly obliterated. The columns of Bertini are made up of the blended lateral portions of the cortex of two contiguous lobes. origins in the Malpighian bodies. The different portions of the tubules present somewhat different characters, and have received special names. THE URINARY ORGANS. 155 The collecting tubes, which open into the calix at the apex of the pyramid, are straight, and lie nearly parallel to each other and to the axis of the pyramid, and, therefore, nearly perpendicular to the base of the pyramid. As they are followed from the apex, in a direction the reverse of that taken by the urine in flowing through them, they branch dichotomously, and the branches become pro- gressively smaller. At the base of the pyramid these straight tubules are collected into bundles that radiate toward the convex surface of the kidney, and are called the " medullary rays." In these, and in the part of the pyramid that is near the boundary- zone, the collecting tubes are associated with other straight portions of the tubules, " Henle's tubes," which will be described pres- ently. From the medullary rays the tubules pass into the region between those rays in the cortical portion of the kidney. This region of the cortex is known as the "labyrinth." Here the tub- ules lose their straight character and become much contorted, form- ing the "second convoluted tubules." They then re-enter the medullary rays, which they descend for a variable distance into the pyramid, constituting the "ascending branches of Henle's tubes," which make a sharp turn, " Henle's loop," and then retrace their course up the medullary rays into the cortical portion of the kidney, "descending branches of Henle's tube." They then pass again into the labyrinth and form the " first convoluted tubules," which finally merge into the structure of the Malpighian bodies, also situated in the labyrinth. In consequence of the passage of tubules from them into the surrounding labyrinth the medullary rays become smaller as they are followed from the base of the pyramid, and eventually disappear before the capsule of the kidney is reached. They are completely surrounded by the labyrinth. If we now follow the course of the urine in its way from the Malpighian body to the outlet of the tubule, we shall find that it passes through the following divisions of the tubule : 1, the "first convoluted tubule;" 2, the "descending branch of Henle's tube;" 3, "Henle's loop;" 4, the "ascending branch of Henle's tube;" 5, the " second convoluted tubule ; " 6, the " collecting tube." Of these, the two convoluted tubules are situated in the labyrinth ; all the rest in the medullary rays and pyramid. All of the portions, with the exception of the convoluted tubules and the loop, are straight and lie parallel to each other (Fig. 131). Before entering more particularly into the structure of the renal 156 NORMAL HISTOLOGY. Fig. 131. Diagram showing the course of the renal tubules within the kidney. (Klein.) A, cortex : a, subcapsular portion destitute of Malpighian bodies ; a', inner portion, also devoid of Mal- pighian bodies. B, boundary. C, portion of the medulla at the base of the pyramid. 1, Bowman's capsule surrounding the glomerulus ; 2, neck of the capsule and beginning of the uriniferous tubule ; 3, first convoluted tubule ; 4, spiral portion of the first con- voluted tubule in the medullary ray; 5, descending limb of Henle's tube; 6, Henle's loop ; 7, 8, 9, ascending limb of Henle's tube ; 10, irregular transition to the second con- voluted tubule ; 11, second convoluted tubule ; 12, transition from second convoluted tubule to the collecting tubule ; 13, 14, collecting tubule, joined below by others to form the excretory duct, which opens at the apex of the pyramid. tubule, it will be best to complete this general sketch by considering the course of the bloodvessels. As has already been said, the vessels enter the kidney between the calices and pyramids and are distributed in branches that lie THE URINARY ORGANS. 157 Fig. 132. parallel to the bases of the latter, and, therefore, to the convex surface of the organ, and are situated in the boundary-zone. The arterial branches in this location form the "arterial arcade." From this arcade per- pendicular branches, the " interlobular arte- ries," pass toward the capsule, taking a straight course through the labyrinth be- tween the medullary rays. In this course they give off branches, the "afferent ves- sels," which go to the Malpighian bodies. Fig. 133. Fig. 132.— Diagram showing the course of the bloodvessels within the kidney. (Ludwig.) a, interlobular artery ; b, interlobular vein ; e, Malpighian body, with the afferent vessel entering it from the interlobular artery, and the efferent vessel leaving it to take part in the formation of the capillary plexus between the renal tubules; d, vena stellata; e, arterue recta?; /, venae rectse; g, capillary plexus around the mouths of the excretory ducts. Fig. 133.— Injected glomerulus from the horse. (Kolliker, after Bowman.) u,, interlobular artery; of, afferent vessel; m, m, capillary loops forming the glomerulus; ef, efferent vessel ; b, capillary network in the labyrinth and medullary rays. The main artery becomes smaller in giving off these branches, and finally ends in terminal afferent vessels (Fig. 132). 158 NORMAL HISTOLOGY. Within the Malpighian body the afferent vessel divides abruptly into a number of capillary loops, which are compacted together to form a globular mass, called the " glomerulus " (Fig. 133). These loops rejoin to form the "efferent" vessel, which is somewhat smaller than the afferent vessel, and leaves the Malpighian body .at a point close to that at which the afferent vessel enters it. Fig. 134. Sketch of a Malpighian body from kidney of a rabbit : a, interlobular artery ; b, afferent vessel ; e, capillary springing from afferent vessel ; d, Bowman's capsule, with epithelial lining reflected upon the surface of the glomerulus ; e, cavity of the capsule into which the watery constituents of the urine are first discharged ; /, beginning of a uriniferous tubule; g, convoluted tubules of the labyrinth. Between these tubules and the capsule are capillary bloodvessels derived from the efferent vessel (which is not shown, but emerges from the capsule near the afferent vessel, on a different level from that repre- sented). These and other structures are held in place by an areolar tissue, containing lymphatic spaces, some of which are represented. Soon after leaving the Malpighian body the efferent vessel breaks up into a second set of capillaries, which lie among the convoluted tubules of the labyrinth and also penetrate into the medullary rays, to be distributed between the tubules composing them. This capil- lary network extends also into the pyramid, in which the capilla- THE VRINARY ORGANS. 159 ries run, for the most part, parallel to the renal tubules, with com- paratively few transverse anastomosing branches. For this reason they have been called the "vasa recta." They also receive blood from little twigs given off from the arterial arcade. The blood from the iutertubular capillaries is collected in veins, which run a course parallel to that of the arteries and lie in close proximity to them. They have received names similar to those of the corresponding arteries : " interlobular veins," " venae recta?," and " venous arcade." Kelatively large veins also leave the kidney from beneath the capsule on the convex surface of the organ. They are called the " stellate veins." The Malpighian body is enclosed by a thin fibrous capsule (Bowman's capsule), which is perforated at two opposite points to permit the passage on the one hand of the afferent and efferent vessels, and on the other hand to allow of a communication between its cavity and the beginning of the uriniferous tubule. When dis- tended with blood the glomerulus nearly fills this capsule, but when collapsed it is retracted toward the attachment formed by the ves- sels that pierce the capsule. It is covered by a single layer of epi- Fie. 135. Pig. 136. Cross-sections of convoluted tubules lined with cells in different states of activity. (Disse.) Fig. 135. — From a criminal directly after execution. Cells in a state of rest. The cells are low and granular, and present a striation of their free ends resembling cilia. Fig. 136.— From a cat. The cells are enlarged, because charged with material to be excreted, and the striated border is nearly obliterated. Similar appearances have been observed in the human kidney. In one of the lower cells in this figure a faint striation of the attached end is just discernible. This increases in distinctness as the cell becomes sur- charged with excretory material, when the more central portion of the cytoplasm becomes hyaline and contains the nucleus. thelial cells, which is reflected at that attachment and forms a lining for the inner surface of the capsule to the point where its cavity opens into the lumen of the renal tubule. Here the epithelial lining becomes continuous with that of the tubule (Fig. 134). The different portions of the uriniferous tubule differ in their 160 NORMAL HISTOLOGY. external diameters, the diameters of their lumina, and the character of their epithelial linings. The appearance of the epithelial cells differs, however, in accordance with their state of functional activity (Figs. 135 and 136). The first convoluted tubule is relatively large, and is lined with large epithelial cells, which project into the tubule about one-third of its diameter. The cells have round nuclei situated near their centres, and are granular, with an appearance of radiate striation in their deeper halves when charged with secretion. The descending branch of Henle's tube has a smaller diameter, but its lumen is wide in consequence of the thinness of the clear epithelial cells lining it. In the ascending branch the lumen is again smaller, although the diameter of the tube is larger, because the lining cells are thicker, somewhat resembling those of the first convoluted tubule. The transition from the character of the de- scending to that of the ascending branch does not always take place exactly at the loop. The second convoluted tubule is a little smaller than the first, and is lined with cells that are not quite so granular and a little more highly refracting. The collecting tubules are lined with columnar epithelium, the cells of which become longer as the diameter of the tube increases in its progress toward the apex of the pyramid. The epithelial lining throughout the course of the renal tubule is said to rest upon a thin, homogeneous basement-membrane inter- posed between it and the interstitial fibrous tissue. The latter is jaresent in small amount, and partakes of the character of an areolar tissue, holding the tubules and bloodvessels in place. It is rather abundantly supplied with lymphatics. For the study of the uriniferous tubules sections made trans- verse to the course of the straight tubules will be found very use- ful. In the cortex the medullary rays, with their descending and ascending branches of Henle's tubes and their collecting tubules, will appear surrounded by the labyrinth, made up of the con- voluted tubules, Malpighian bodies, and larger vessels, the latter in cross-section. Near the apex of the pyramid cross-sections of the larger collecting tubes and of the vasa recta will be seen ; and near its base the smaller collecting tubes and the two limbs of Henle's tube, with, possibly, here and there a "loop" in nearly longitudinal section, will appear. Among all these sections of the tubules the THE URINARY ORGANS. 161 interstitial tissue with its capillaries and lymphatics will complete the picture (Figs. 137 and 138). Fig. 137. Fig. 138. Sections from a rabbit's kidney, made perpendicular to the course of the straight tubules. Fig. 137. — Through a portion of the pyramid : a, lower portions of the collecting tubules (excretory ducts) ; 6, Henle's loop in tangential section ; c, capillary bloodvessels ; d, lymphatic ; e, descending limb of Henle's tube. Fig. 138. — Through part of a medullary ray and the adjoining labyrinth : a, a, a, a, convoluted tubules in the labyrinth ; b, spiral tubule ; c, descending limb of Henle's tube ; d, ascend- ing limb of Henle's tube : e, irregular tubule ; /, collecting tubule ; g, capillary blood- vessel. The nerves of the kidney are small and apparently not abundant. Their larger branches follow the courses of the arteries. 11 162 NORMAL HISTOLOGY. The external surface of the kidney is covered with a capsule of fibrous tissue, which on its deeper surface becomes continuous with the interstitial tissue, so that its vascular supply communicates with the capillaries in the superficial portions of the kidney. The fibrous capsule of the kidney becomes continuous at the hilum of that organ with the fibrous coats of the calices and pelvis, and, through these, with those of the ureter and bladder. The columnar epithelium lining the collecting tubes is continuous with a layer of similar cells covering the papillse. The watery constituent of the urine is secreted in the Malpighian body, where it passes from the blood through the capillary walls of the glomerulus into the cavity of Bowman's capsule. Under nor- mal conditions it is free from albumin, and, therefore, is unlike the serum that passes through the walls of the capillaries in other parts of the body. It has been thought that this difference was attrib- Fig. 139. ^ Capillary loop from the glomerulus of the frog. (Nussbaum.) Ez, endothelial wall of the capillary bloodvessel; Ek, nucleus of one of the endothelial cells (only three such nuclei are shown in the figure) ; KE, nucleus of one of the epithelial cells investing the capillary. The boundaries of these cells are not reproduced in the figure. At the left of the cut three epithelial cells have been partially reflected away from the capillary wall. utable to the functional action of the endothelium in the o-lomerulus though morphologically it is similar to that throughout the body. It is more probable that the epithelium covering the glomerulus has THE URINARY ORGANS. 163 something to do with the prevention of a loss of albumin (Fig. 139). In disease of the kidney, alterations in the glomerulus and, per- haps, in other parts of the kidney permit albumin to pass into the secretion. The epithelium lining the uriniferous tubules discharges its secretion into the lumen of the tubules, whence it is carried by the stream flowing from the Malpighian bodies. The epithelial cells lining the convoluted tubules and the ascending branches of Henle's tubes appear to be those most active in carrying on the eliminative function of the kidney. 2. The pelvis of the kidney and its calices are lined with trans- itional epithelium. It consists of only three or four layers of epithelial cells of different shapes. The most superficial layer is composed of rather large flattened cells, having ridges upon their lower surfaces, which fill the spaces between the tops of the next layer. This is made up of pear-shaped or caudate cells, the hemi- spherical tops of which fit into the cavities between the ridges on the layer above, while their slender processes penetrate between Fig. 140. Epithelial cells from the pelvis of a human kidney. (Rieder.) the oval or round cells that make up the deepest layers of the epithelial covering (Fig. 140). Beneath the epithelium is a coat of fibrous tissue, denser near the epithelium and more areolar in its deeper portions. Here it is 164 NORMAL HISTOLOGY. outside of which is the interlaced with smooth muscular fibr external coat of fibrous tissue. 3. The ureters closely resemble in structure the pelvis of the kidney; but the muscular fibres have a somewhat more definite arrangement, being disposed in an inner imperfect coat of longi- tudinal and an external layer of circular fibres, outside of which a few supplementary longitudinal fibres are, here and there, added (Fig. 141). 4. The bladder also has a lining of transitional epithelium (Fig. Fig. 141. Epithelial cells from the human ureter. (Rieder 40), beneath which is a layer of fibrous tissue resembling that of the renal pelvis, but of greater thickness. The muscular coat, which comes next, is thick and composed of bundles of smooth muscular fibres, interlacing in various directions or disposed in more or less well-defined strata. External to the muscular coat is a fibrous coat, which is covered by a reflection of the peritoneum for a part of its extent, and in other situations passes into the sur- rounding areolar tissue. The spear-shaped cells of the transitional epithelium of the blad- der have thicker processes than those of the pelvis or ureter; but when detached and macerated in the urine it is often very difficult to determine from their appearance from what part of the urinary tract such cells were derived (Figs. 142 and 143). THE URINARY ORGANS. 165 5. The urethra differs in structure in the two sexes. In the male the prostatic portion is lined with epithelium resembling that Fig. 142. '•&:~. ■■-sage of nutrient fluids. CHAPTER XIII. THE RESPIRATORY ORGANS. The respiratory tract consists of the larynx, trachea, bronchi, and lungs. 1. The Larynx. — The interior of the larynx is lined with ciliated columnar epithelium, which extends over the false vocal cords and about half-way up the epiglottis above, and is continuous below with a similar lining throughout the trachea and bronchi. This lining is interrupted over the true vocal cords by a covering of stratified epithelium, and at its upper limits passes into the stratified epithelium lining the buccal cavity and pharynx and covering the tongue. Opening upon this epithelial surface, except upon the true vocal cords and in the smallest bronchi, are mucous glands, varying in number in different situations. Some of the columnar cells upon the surface are also mucigenous, discharging their secretion upon the free surface of the mucous membrane. The thyroid, cricoid, and most of the arytenoid cartilages are composed of the hyaline variety of that tissue : the epiglottis, cornicula laryngis, and the apices of the arytenoids, of elastic car- tilage. Beneath the epithelium lining the laryngeal ventricle is a con- siderable layer of lymphadenoid tissue. In other situations the epithelium rests upon fibrous tissue. 2. The Trachea. — The tracheal wall may be divided into four coats : a, the mucous membrane ; b, the submucous coat ; c, the cartilage; d, the fibrous coat (Fig. 145). a. The mucous membrane is covered with ciliated columnar epi- thelium resting upon a nearly homogeneous basement-membrane, beneath which is a layer of fibrous tissue. This may be divided into two portions : an outer one, next to the basement-membrane, which is areolar in character, with a large admixture of elastic fibres and lymphadenoid tissue, and an abundant supply of blood- vessels ; and an inner one, less highly vascularized, and composed chiefly of elastic fibres running a longitudinal course. THE RESPIRATORY ORGANS. 169 b. The submucous coat is of areolar fibrous tissue, supporting the mucous glands that open into the trachea, and the bloodvessels, lymphatics, and nerves, and also little masses of adipose tissue. In the neighborhood of the cartilages this fibrous tissue becomes con- densed to form the perichondrium. c. The cartilages are composed of the hyaline variety of that Fig. 145. o < . MH9K ■ From a longitudinal section through the trachea of a child. (Klein.) a, the stratified columnar ciliated epithelium of the internal free surface ; b, the basement -membrane ; c, the mucosa (tunica propria) ; d, the network of longitudinal elastic fibres (the oval nuclei between them indicate connective-tissue corpuscles) ; e, the submucous tissue, con- taining mucous glands ; /, large bloodvessels ; g, fat-cells : h, hyaline cartilage of the tracheal rings. (Only a part of the tracheal wall is given in the figure.) tissue, and are incomplete rings, interrupted behind, where the two ends are united by a band of smooth muscular tissue. d. The fibrous coat is of areolar tissue beyond the bounds of the perichondrium, and serves to connect the trachea with its sur- roundings. 3. The Bronchi. — The main bronchi branching from the trachea have a structure similar to that organ, but the cartilaginous rings become more delicate as the tubes diminish in size. 170 NORMAL HISTOLOGY. The smaller bronchi differ in structure from the trachea in possessing a muscularis mucosae, with its fibres disposed in a circular direction, and having irregular cartilaginous plates in their walls, instead of C-shaped, imperfect rings. The four coats may be enumerated as follows : a. Mucous membrane, covered with ciliated columnar epithelium resting upon a basement-membrane, beneath which is a fibrous tissue containing numerous elastic fibres lying parallel to the axis of the bronchus. Under this are the circular fibres of the mus- cularis mucosa. b. Submucous coat, similar to that of the trachea and larger bronchi. c. Cartilaginous coat, containing the plates of cartilage that sup- port the walls. d. Fibrous coat of areolar tissue, containing a little adipose tissue and passing into the areolar tissue of neighboring structures. As the bronchi subdivide and become smaller the coats get thinner, and first the cartilaginous and then the muscular coat dis- appears. Those air-passages which are without cartilage, but have Fig. 146. Portion of a cross-section of a bronchiole from the lung of a pig. (Sohultze.) a, areolar external coat ; b, muscularis mucosa? : c, subepithelial areolar tissue, containing numerous longitudinal elastic fibres, represented here in cross-section ; tf, ciliated epithelium, form- ing the most superficial layer of the mucous membrane ; /, walls of the neighboring pul- monary alveoli. In these walls branching and anastomosing elastic fibres are shown ; the capillary plexus has been omitted. a muscularis mucosae, are called "bronchioles" (Fig. 146). The still smaller branches, which have lost their muscular tissue, are known as the "alveolar passages." In the latter the columnar THE RESPIRATORY ORGANS. 171 epithelium lining the bronchi gives place to a pavement-epithelium, composed of small flattened cells disposed in a single layer. The elastic tissue of the mucous membrane is continued through all the divisions of the air-passages, and becomes a constituent part of the alveolar walls of the lung itself. The alveolar passages open into spaces, called the " infundibula," in the sides of which are the openings into the alveoli of the lung, the ultimate destination of the inspired air. Here and there Fig. 147. t^M^ A-r- Section of lung of the dog, showing a transverse section of a bronchiole : a, bronchiole (a little mucus covers the epithelial lining) ; 6, muscular layer of the mucous membrane ; c, c, radicles of the pulmonary vein ; d, alveolar massage, just at its division to form infun- dibula. An infundibulnm extends from this passage toward the bronchiole. The wall of the alveolar passage at this point is similar in structure to that of the pulmonary alveoli, e, alveolar passage in oblique section. This passage is cut at a point further from its opening into the infundibula, and has a somewhat thicker wall than d. The rest of the section is made up of infundibula (the larger spaces) and pulmonary alveoli. stray alveoli open directly into the alveolar passages (Figs. 147, 148^ and 149). 4. The pulmonary alveoli and the smaller air-passages are so arranged that there are no vacant spaces ; and neighboring alveoli, whether they belong to a group of infundibula springing from the same alveolar passages or to separate groups, are so closely situated that they have but one common wall dividing their cavities 172 NORMA L HISTOL Y. from each other. Notwithstanding this general compactness of arrangement, the lungs are divided by delicate septa of fibrous tissue into more or less well-defined lobules, corresponding to the smallest bronchi or the bronchioles. The alveolar walls are made up of a delicate, loose areolar tissue, containing numerous elastic fibres and supporting the abundant capillary plexus in which the blood suffers the gaseous exchanges with the air that constitute the function of respiration (Fig. 150). Fig. lis. b-J- Section of lung of the dog : a, alveolar passage opening into an infundibulum and also into a solitary alveolus ; b, cross-section of an infundibulum. The dotted line indicates the limits of the infundibular space. Opening into it are a number of alveoli. Were the dotted line removed, the infundibular cross-section and the alveoli around it would form a stellate space in the section, c, junction of two radicles of the pulmonary vein. At the top of the section, to the right, is an oblique section of a bronchiole. Covering the two surfaces of the alveolar wall is a layer of very thin cellular plates (pavement-epithelium, see Fig. 30), among which are scattered a few cells resembling those lining the alveolar passages. This cellular investment is continuous with the lining of the infundibulum, which is of similar character, and thence with the epithelium covering the inner surface of the alveolar passage. It is to be regarded as a special modification of epithelium, fitting it for usefulness in this situation. THE RESPIRATORY ORGANS. 173 The lung receives blood from two sources : 1, venous blood, through the pulmonary artery, which is oxygenated in the walls of the alveoli ; 2, arterial blood, through the bronchial arteries. This arterial blood serves for the nourishment of the tissues of the lung and is distributed to the bronchi, interlobular connective tissue, lymph-glands, and walls of the vessels. Part of this blood returns through the pulmonary veins ; the rest through the bronchial veins. Fig. 149. — -& Section of lung of the dog : a, oblique section of a bronchiole ; 6, its muscular coat ; c, longi- tudinal section of an infundibulum. communicating to the right with an alveolar passage (the wall of the latter is torn further to the right) ; d, one of the alveoli opening into c. The lymphatics arise in the walls of the alveoli and bronchi and pass to the bronchial lymph-glands. The nerves supplying the lung may be traced along the bronchi, where they occasionally connect with groups of ganglion-cells, and along the vessels. They are of both the mednllated and the non- medullated varieties. The surface of the lung is covered with serous membrane, a por- tion of the pleura. Little need be said about the functional activity of the lung. The cilia, belonging to the columnar epithelium lining nearly the 174 NORMAL HISTOLOGY. whole of the air-passages, possess a motion that urges particles lodging in the mucus covering them toward the larynx, whence they are either coughed out or are swallowed. Such solid particles as pass beyond the regions guarded by ciliated epithelium are taken up by leucocytes, which frequently migrate into the alveoli and the air-passages, and are conveyed by them into the lymphatic vessels or glands. Because of this the lymphatics and bronchial lymphatic nodes are apt to be blackened by the deposition of carbon, except in young individuals. The flow of air into the lung is the result of atmospheric pressure, which tends to fill the thoracic cavity when the Fig. 150. Section of the lung of a dog, killed by ether-narcosis. The lung was hypereemic at the time of death, and the capillaries retain their blood in the section, a, alveolus in cross-sec- tion, communicating with the infundibulum, b. A portion of the wall of the alveolus is seen, in surface-view, at c. d, e, other alveoli opening into the same infundibulum ; /, cross-section of an infundibulum with alveoli opening into it ; g, surface-aspect of an alveolar wall, showing capillary plexus filled with red blood-corpuscles. chest is expanded through the action of the muscles of respiration. The air is expelled from the lungs when those muscles relax, partly because of the pressure exerted by the thoracic walls, but chiefly because of the contraction of the elastic fibres in the alveolar walls. THE RESPIRATORY ORGANS. 175 Because of their presence the lungs retract when the chest is opened. When sections of the lung are examined under the microscope it is difficult, at first, to identify the different portions, which are cut in all directions. The smaller bronchi may be recognized by the presence of cartilage in their walls. The bronchioles pos- sess no cartilage, but are surrounded by a band of smooth mus- cular tissue, the muscularis mucosae. This becomes thinner, then incomplete, and finally disappears as the infundibula are reached. The infundibulum, it will be remembered, is the space into which the alveoli open. When seen in section it will appear as a round, oval, or elongated space, according to the direction in which it has been cut, bounded by scallops, each of which is the cavity of an alveolus. In every section there will be many alveoli which have been so cut that their openings into the infundibulum will not be included in the section. These alveoli have a continuous wall surrounding their cavities. Still other alveoli will have been cut in such a way that a portion of their walls will lie in the plane of the section and parallel to it, so that the flat surface of the alveolar wall will be visible, surrounded by an oblique or cross-section, where the wall meets the surface of the section. Those alveolar walls which have been cut perpendicular to their surfaces will appear thinner than those which have been cut obliquely. With these considera- tions in his mind, the student can have little difficulty in identify- ing the different portions of the section (see Figs. 147-150). CHAPTER XIV. THE SPLEEN. Nearly the whole surface of the spleen is invested with a cov- ering of peritoneum similar to that which partially covers the liver. Beneath this is the true capsule of the spleen, which com- pletely surrounds it. This capsule is composed of dense fibrous tissue, containing a large number of elastic fibres and a few of smooth muscular tissue. From its inner surface bands of the same tissue, called the " trabecule," penetrate into the substance of the organ, where they branch, and the branches join each other to form a coarse nicshwork occupied by the parenchyma of the organ, the " pulp." The bloodvessels of the spleen enter at the hilum and pass into the large trabeculae, which start from the capsule at that point and enclose the vessels until they divide into small branches. The vessels then leave the trabecular and penetrate the pulp, where they break up into capillaries, which do not anastomose with each other. There is some doubt as to the way in which these capillaries end. According to one view, they unite to form the venous radicles, so that the blood is confined within vessels throughout its course in the spleen. Another view, which is more probably correct, is that the walls of the capillaries become incomplete, clefts appearing between their endothelial cells, which finally change their form and become similar to those of the reticulum of the pulp. The veins, accord- ing to this view, arise in a manner similar to the endings of the arteries. The result of this structure would be that the blood is discharged, from the capillary terminations of the arteries, directly into the meshes of the pulp, after which it is taken up by the capillary origins of the veins (Figs. 151 and 152). The pulp consists of a fine reticulum of delicate fibres and cells, with branching and communicating processes, in the meshes of which there are red blood-corpuscles, leucocytes in greater number than normally present in the blood, and free amoeboid cells consid- erably larger than leucocytes, called the " splenic cells." 176 THE SPLEEN. 177 The adventitia of the arteries contains considerable lympbadenoid tissue, which after the exit of the vessels from the trabeculse is Fig. 151. Section from the spleen of the cat. (Bannwarth.) Termination of an arterial capillary in the pulp. expanded at intervals to form spherical bodies, about 1 mm. in diam- eter, called the " Malpighian bodies" or "corpuscles." These are Fio. 152. Section from the spleen of the cat. (Bannwarth.) Beginning of a capillary venous radicle. like little lymph-follicles, through which the artery takes its course. The reticulum in these Malpighian corpuscles is scanty and incon- 12 178 NORMAL HISTOLOGY. spicuous near their centres, so that the lymphoid cells it contains appear densely crowded ; but toward their peripheries the reticulum is more pronounced and the cells a trifle more separated. At the surface of the Malpighian body its reticulum becomes continuous with that of the pulp surrounding it (Fig. 153). Fig. 153. Section from human spleen. (Kolliker.) A, capsule ; b, b, trabeculae ; ! V Injected lymphatics in an adrenal body of the ox. (Stilling.) £, injection-mass within the lymphatic vessels; N, cross-section of ><■ nerve; V, longitudinal section of » vein. Lymphatic radicles are seen among the epithelial cells (cortical variety free from fat) to the right of the figure. the medulla. At the junction of the medulla and cortex the nerve-fibres are connected with ganglion-cells. The nerve-termi- THE DUCTLESS QLANJ)S. 189 nations are distributed to the walls of the vessels and penetrate between the epithelial cells of the parenchyma. As in the case of the thyroid gland, the relations of the epithelial cells of the adrenal bodies to the lymphatics appear of special interest. The lymphatic vessels are abundant and large, and accom- pany the bloodvessels lying in the areolar tissue of the septa. Here they come into close relations with the columns of epithelial cells, and, at least in the cortex, send minute terminal branches into those columns, where they end among the epithelial cells (Fig. 164). This arrangement of the lymphatics appears to point to the elaboration of an internal secretion as the function of the adrenal bodies. Small masses of lymphadenoid tissue are occasionally observed in the cortical portion of the adrenal body. 4. The Pituitary Body. — The pituitary body (hypophysis cerebri) is divisible into two portions, which differ both in their structure and in their embryonic origins. The posterior, or nervous, lobe is derived from a prolongation of the third cerebral ventricle. The anterior, or glandular, lobe develops from a tubular prolongation, lined with epithelial cells, from the buccal cavity of the embryo. This partially or completely invests the nervous portion of the body, but its chief bulk is situated in front. The connection with the buccal cavity is obliterated, and, in the further development of the detached portion, a number of anastomosing columns of epi- thelial cells are formed, which are separated from each other by septa of vascular areolar tissue. These septa become continuous at the periphery with a thin fibrous capsule furnished by the pia mater. The cells of the epithelial strands in the glandular lobe appear to be of two sorts, which, like those in the thyroid gland, probably represent different stages of functional activity. The darker sort of cell yields microchemical reactions resembling those of colloid ; and little masses of colloid, presumably derived from those cells, are of not infrequent occurrence within or at the margins of the epithelial columns (Figs. 165 and 166). The glandular lobe is richly supplied with capillary bloodvessels in intimate relations with the epithelium, from which they often appear to be separated by only a thin basement-membrane, and the existence of this is doubtful in some situations (Fig. 167). The above description shows that the structure of the hypophysis is similar to that of the other ductless glands already considered. 190 NORMAL HISTOLOGY. Fig. 165. Section from the hypophysis of the ox. (Dostoiewsky.) -d, veins ; a, alveoli or cell-columns, with pale, relatively clear cytoplasm; b, alveoli or columns of darker granular cells. Other cell-groups contain both varieties of cell. Fin. 166. ection from the glandular lobe of the hypophysis : horse. (Lothringer.) Showing the darker cells at the periphery of the epithelial strands, and the clearer cells, for the most part, in their centres. THE DUCTLESS QLANDiS. 191 Its function is still very obscure ; but it appears, in cases of experi- mental thyroidectomy and in disease of the thyroid in the human subject, to enlarge when the function of the thyroid gland is abol- ished and to assume vicariously the duties of that organ. In how far this points to a normal similarity in function of the two organs must, at present, be left undetermined. In eases of enlargement of the pituitary body profound changes in nutrition, characterized chiefly by overgrowth, frequently take place in the bones of the skeleton (acromegaly). The nervous supply of the anterior lobe consists of non-medul- Fig. 167. Section from the glandular lobe of the hypophysis ; child six months old. (Lothringer.) The close relations between the epithelial cells and the capillary bloodvessels, and the differences in the cells, are indicated in this figure. The red blood-corpuscles within the capillaries have been stained dark. lated fibres, destitute of ganglion-cells, which ramify about the vessels and send some of their terminal twigs between the epithelial cells. The posterior lobe consists of tissues resembling those of the central nervous system : ganglion-cells, non-medulla ted fibrils, and neuroglia-cells. Within its substance there are also peculiar oval bodies surrounded by nervous terminations, to which sensory func- tions have been attributed, and small follicles, lined with cubical epithelium. 192 NORMA L IIISTOL C ) '. 5. The Thymus. — This organ reaches its fullest development at about the second year of life, after which retrograde changes, end- ing in the substitution of fibrous and adipose tissues for its proper structure, take place. Its development la-gins as an ingrowth of epithelium from the branchial clefts. This epithelium forms a Fig. I US. Two concentric corpuscles of Ilassall, from the fa-tal thymus. (Klein.) branching, solid column of cells surrounded by embryonic connec- tive tissue, which develops into lyniphadenoid tissue. In the meantime the epithelial strands are broken up and the whole organ becomes converted into a structure resembling a collection of lymph- follicles, but with this difference : that remnants of the epithelial strands remain in the centres of many of the follicles, where their Lobule from the thymus of a child. (SchiillVr.) tr, trabccula; o, nodule of denser lymph- adenoid tissue at periphery ("cortex"); b, b, sections of vessels within the less dense lyniphadenoid tissue in the centre ("medulla"); c, c, concentric corpuscles of Hassall. cells become flattened and imbricated. These epithelial masses are known as the concentric corpuscles of Hassall (Fig. l(iS). The thymus is enclosed in a fibrous capsule, which penetrates its substance, dividing it into lobes and lobules. Each of these lobules closely resembles a lymph-follicle, but it is doubtful whether lymph- THE DUCTLESS GLANDS. 193 sinuses, corresponding to those in the lymphatic nodes, are present in the thymus (Fig. 169). The function of the thymus is still a matter of doubt. It has been regarded as one of the sites in which red blood-corpuscles are formed, and also as a temporary lymphadenoid organ playing the part of the lymph-nodes until these have become fully developed in other parts of the body. The thymus is connected with the thyroid by a strand of thymus- tissue, and isolated thymus-lobules are found embedded in the edges of the thyroid, near the parathyroid body (see Fig. 159). The bloodvessels ramify in the septa of the organ and send branches into the lymphoid follicles. The lymphatic vessels accom- pany the bloodvessels and surround the lobules, but do not appear Fig. 170. ' — m& '*?$•> te&Jv . ~- V 9 '~^/ Section of the carotid gland and carotid arteries near their origin. (Marchand.) ci, internal carotid ; re, external carotid ; gle, carotid gland ; I, I, groups of epithelial cells ; i, fibrous tissue between the epithelial groups ; g, bloodvessel. Numerous vessels are also seen within the gland. to penetrate into the lymphadenoid tissue. The nerves are small and not numerous. They accompany the bloodvessels, but nervous terminations have not been traced as distributed to the lymphade- noid tissue. The involution of the gland appears to be accomplished through 13 194 NORMAL HISTOLOGY. Fig. 171. ®'& kM\ 'fh Portion of the same gland as Fig. 170, more highly magnified : p, epithelial cells ; g, capillary bloodvessels ; e, endothelium forming the capillary wall. a proliferation of the fibrous tissue around the lobules, which en- croaches upon the Iymphadenoid tissue and gradually replaces it. This fibrous tissue subsequently becomes, in great measure, con- verted into adipose tissue. It appears as though the endothelium of the bloodvessels also proliferated, giving rise to masses of irnbri- Fig. 172. Section of the coccygeal gland. (Sertoli.) The group of cells, apparently of epithelial nature, is traversed by small bloodvessels and enclosed by fibrous tissue. cated cells within the follicles and leading to an obliteration of the vascular lumen. 6. The Carotid Glands. — These consist of groups or islets of epithe- lial cells, surrounded by fibrous tissue from which numerous capil- THE DUCTLESS GLANDS. 195 lary bloodvessels are distributed in close relation with the epithelial cells (Figs. 170 and 171). Their function is unknown. 7. The Coccygeal Gland. — This body is made up of groups and strands of cells, probably of epithelial nature, closely applied to the walls of capillary bloodvessels and surrounded by fibrous tissue. Its function and mode of origin are both unknown (Fig. 172). CHAPTER XVI. THE SKIN. The skin consists of a deeper, fibrous portion, the corium, or true skin, and a superficial, epithelial layer, the epidermis. As a part of the latter, and developing from it, the skin contains two sorts of glands, the sebaceous and the sweat-glands, and two kinds of appendages, the hairs and nails. The corium is composed of vascularized fibrous tissue, which is Fig. 173. Section of skin perpendicular to the surface. (Arloing.) u, horny layer of the epidermis ; 5, rete mucosum ; c, surface of the corium ; d, sebaceous gland ; e, areolar tissue of the corium ; /, hair-shaft "within the hair-follicle ; g, lohule of adipose tissue in the subcu- taneous tissue ; h, sweat-gland ; mh, arrector pili ; p, papilla of the corium extending into the rete mucosum. The lower limit of the corium is not marked by a plane parallel to that of the surface of the skin. The corium may be said to end where the fat of the sub- cutaneous tissue begins. made up of bundles loosely arranged in its deeper portions, where it becomes continuous with the subcutaneous areolar tissue, and contains 196 THE SKIN. 197 a variable amount of fat, but more compactly disposed in the super- ficial portions, where it comes in contact with the epidermis, into which it projects in the form of papillae. Some of these papillae contain loops of capillary bloodvessels, while others are occupied in their centres by peculiar nerve-endings, called " tactile corpus- cles." In some situations, notably upon the palms and soles, the papillae of the corium are arranged in rows. In most parts of the skin they are irregularly scattered over the surface of the corium (Fig. 173). The epidermis (Fig. 174) is a layer of stratified epithelium in Fig. 174. Vertical section of the epidermis of the finger. (Kanvier.) a, stratum corneum, or horny layer ; b, stratum lucidum ; c, stratum granulosum ; d, rete mucosum ; e, " prickles " on the cells bordering on the corium, which is not represented. which the cells multiply, where they are situated near the corium, and gradually suffer a conversion into horny scales as they are pushed toward the surface, where they are eventually desquamated. The changes the cells undergo in their journey from the deeper layers of the epidermis to its surface cause variations in their appearances which have occasioned a division of the epidermis into a number of more or less well-defined strata. The deepest stratum, where the cells multiply and grow, is called the " rete mucosum." It is composed of cells which gradually enlarge, becoming rich in cytoplasm, and are connected with each other by minute cytoplas- mic " prickles," between which there is a space affording a channel for the circulation of nutrient fluids (Fig. 39). Above the rete mucosum the cells appear more granular, owing to the formation 198 NORMAL HISTOLOGY. of a substance, called "eleidin," within the cytoplasm (Fig. 175). These cells form the "stratum granulosum." The eleidin appears to be produced at the expense of the cytoplasm, the process being a form of degeneration, so that after a while the whole cell is con- verted into a homogeneous material in which the nucleus persists in a form deprived of chromatin, and therefore insusceptible of staining. The presence of these cells gives rise to the formation of the " stratum lucidum " immediately above the stratum granulosum. Within this stratum the eleidin appears to pass into a closely related substance of a horny nature, keratin, and the cells become con- Fig. 175. Cell from the stratum granulosum of the epidermis of the scalp. (Rabl.) The cytoplasm of the cell has been in great measure converted into granules of eleidin ; the chromatin of the nucleus has retracted into a compact mass in the centre of the nuclear region, and is destined to disappear. This cell is from a section made parallel to the surface of the epidermis, which accounts for its shape and apparent size. verted into firmly compacted scales, which make up the most super- ficial or horny layer of the epidermis. The sweat-glands are simple tubular glands, the deep ends of which are irregularly coiled to form a globular mass situated in the deeper portion of the corium or at various depths in the sub- cutaneous tissue. From these coils the excretory duct passes through the corium to the epidermis, where it opens into a spiral channel between the epidermal cells, ending in an orifice at the sur- face of the skin. The epithelial lining of the sweat-gland is a continuation of the stratum mucosum, from which it is derived, and consists of two or more layers of cubical cells in the duct and of a single layer of more columnar cells in the deeper, secreting portion of the gland. In the duct these cells rest upon a homogeneous basement-membrane, but in the secreting portion there is a more or less complete layer of elongated cells, similar in appearance to those of smooth muscular tissue, which lie between the epithelial cells and the basement-mem- brane (Fig. 176). It is doubtful whether these are really muscle- cells. The loops of the glandular coil are surrounded by fibrous tissue, which contains the bloodvessels supplied to the gland and serves to support it in its globular form. THE SKIN. 199 The sebaceous glands can best be described in connection with the hairs and their follicles. The bulbous attachment, or " root," of the hair, and the adjacent portion of its shaft, are contained in an invagination of the corium and epidermis, called the " hair-follicle " (Fig. 173,/). This is sur- rounded by fibrous tissue, forming its external coat, which may be imperfectly distinguished into an outer layer, containing relatively abundant longitudinal fibres, and an inner layer, in which encircling Fig. 176. Section through the coiled end of a sweat-gland. (Klein.) a, 6, duct in longitudinal and cross-section ; c, d, sections of the secretory portion of the tubule. Above d is a little adi- pose tissue. The rest of the section is composed of vascularized areolar tissue. fibres predominate. At the bottom of the follicle this fibrous tissue becomes continuous with that of a vascularized papilla, similar to those existing on the surface of the corium, which projects into the root of the hair. The fibrous sac constituting the outer part of the hair-follicle is lined with a continuation of the epidermis, leaving a cylindrical cavity occupied by the hair. This layer of epithelium is reflected upon the surface of the papilla, Avhere it forms the root of the hair, and then passes into the shaft, which is made up of cells, derived from those of the root, that have suffered keratoid degeneration. The epithelium lining the follicle, as well as that which composes the hair, is not of uniform character throughout, and has been divided into a number of layers, to which different observers have given special names. The group of cells surrounding the papilla are the seat of the multiplication which results in the growth of the hair. Upon the surface of the shaft these cells become transformed into 200 NORMAL HISTOLOGY. thin scales, each of which overlaps that above it. This very thin Fig. 177. t; m'\ '. J\ . — — i m. mmmL mm fifty Ki^''' /V Hair-follicle from the human scalp. (Mertsching.) Longitudinal axial section through the fundus : a, b, longitudinal and encircling layers of the fibrous coat ; c, hyaline layer, formed of an outer faintly fibrillated and an inner more homogeneous lamina; d, papilla; e, outer root-sheath, continuous with rete mucosum of epidermis ; e', its outer layer, continuous with deepest cells of rete and with columnar cells covering the papilla ; e", its inner layer, continuous with the cortical cells of hair ; /, Henle's sheath ; g, Hux- ley's layer; h, cuticle of root-sheath ; k, cuticle of hair; I, cortical cells of the hair; m, medulla. layer is called the " cuticle " of the hair. Beneath the cuticle the cells are crowded together into fusiform or fibrous elements, which THE SKIX 201 make up the chief mass of the hair-shaft. In the centre of this mass there is sometimes a line of more loosely aggregated cells, forming the " medulla " of the hair. When this is present the sur- rounding part of the shaft, between it and the cuticle, is known as the "cortex" (Figs. 177 and 178). The sebaceous glands (Fig. 173, d) are sacculations in the corium near the hair-follicles, which are filled with epithelial cells. The cells at the periphery divide, and, as they increase in size, push Fig. 178. - --.-Sri 8P ; v;^^^& Hair-follicle from the human scalp. (Mertsehing.) Cross-section from middle third of the follicle: &, longitudinal and encircling layers of the nitrous coat; c, hyaline layer, formed of an outer faintly fibrillated and an inner more homogeneous lamina, cf ; e, outer root-sheath, continuous with rete mucosum of epidermis ; /, Henle's sheath ; g, Huxley's layer; h, cuticle of root-sheath; k, cuticle of hair; I, cortical cells of the hair; m, medulla. each other toward the centres of the sacs. Here they undergo a fatty degeneration, ending in destruction of the cells and the forma- tion of an oily secretion, the sebum, which is discharged into the hair-follicle a short distance below its opening on the surface of the skin. The sebum is a lubricant for both the hair and the epi- dermis (Fig. 179). The color of the epidermis and of the hair is due to a pigmenta- tion of the cells in the deeper layers of the rete mucosum and those composing the hair. The whiteness of the hair which comes with years is due to little spaces which appear in unusual numbers between the cells of the cortex, and are filled with air, reflecting the light and masking the pigmentation of the cells. The nails are especially thick and condensed masses of epithelial cells which have undergone keratoid degeneration and are closely compacted. They are produced at the root of the nail, and as they 202 NORMAL HISTOLOGY. Fig. 179. Sebaceous gland from the external auditory canal. (Benda and Guenther's Atlas.) a, epi- thelium continuous with that lining the hair-follicle ; b, layer of proliferating epithelium lining the sac of the gland; c, enlarged cell beginning to undergo fatty metamorphosis of the cytoplasm ; d, mass of sebum derived from a single epithelial cell. accumulate push the body of the nail forward. They, therefore, Fig. 180. Section through the root of the nail of a sixth-months fcetus. (Ernst.) a, matrix of the nail formed by an invagination of the rete mucosum. Near the point indicated by the letter the epithelial cells have begun to change into keratoid material, o, loosened scales of the surface of the nail ; o, remains of the fcetal cuticle which have not become keratoid. The letter a and line proceeding from it both lie in the corium. correspond to the horny layer of the epidermis, which has become modified to form these special structures (Fig. 180). THE SKIN. 203 The skin contains little muscular bands, the arrectores pili (Fig. 173, mil), composed of smooth muscular fibres, which are attached to the fibrous coat of the hair-follicles near their deep extremities and to the superficial layer of the corium on the side of the fol- licle toward which the hair leans. The action of these mus- cles is to cause the hair to assume a more vertical position, and to raise it and the follicle, producing the effect known as " goose flesh." By their contraction they may also aid in the discharge of sebum, since their fibres often partially invest the sebaceous glands. The functions of the skin have reference to its being the organ coming in contact with the external world. The epidermis protects the underlying tissues from mechanical and chemical injury and from desiccation. The keratin in its horny layer forms an imper- vious and tough investment of the body, which is highly resistant toward chemical action and mechanical abrasion, and is constantly renewed from the layers that lie beneath it. It is kept in a pliable condition by the sebum discharged upon its surface and by the moisture proceeding from the sweat-glands, the " insensible perspi- ration." The skin also plays a prominent role in the regulation of the bodily temperature. When its vessels are contracted the amount of heat given off from the surface of the body is reduced ; when they are dilated, it is increased. A further loss of heat is occa- sioned by an increased secretion of sweat, which bathes the surface of the skin and abstracts from the body the heat required to con- vert it into vapor. Under the influence of sudden and marked cold the vessels of the skin become much contracted and the arrectores pili shorten, occasioning the production of a roughness of the skin, goose-flesh, and probably also a discharge of se- bum, which reduce the evaporation from the skin. At the same time a reflex rhythmical contraction and relaxation of the volun- tary muscles is brought about — shivering, which increases the liberation of stored energy within the body, and causes it to appear as heat. In conjunction with these functions the skin is also an organ of tactile and thermal sensation, functions which are not merely beneficial in themselves, but are useful auxiliaries in the furthering of the other functions exercised by the skin. It is a common experience that the sensation of cold stimulates the desire for muscular exercise, of which the liberation of heat is a result. The sensation of pain often gives timely warning of exposure to an 204 NORMAL HISTOLOGY. injury sufficiently great to overcome the usual protective powers of the epidermis. Thus we see that when the automatic action of the skin is inadequate for the performance of its functions it calls forth Fig. 181. m Hair-rudiment from an embryo of six weeks. (Kolliker.) a, horny layer of epidermis ; 6, Malpighian layer, rete mucosum ; /, limiting membrane ; m, m t cells extending from the rete mucosum to fill the future hair-follicles. The elongated cells near the base of the sac are those from which hair is developed. The secreting glands of the body arise from some epithelial layer in a similar manner. an auxiliary activity of other organs, through the medium of the nervous system. The hair-follicles are developed from the rete mucosum of the epi- dermis, and first appear as little masses of cells growing into the !'} '"•"'■' •'' * ..*'■ ' Vee.— i~ much more rapid in ease the ovum is not impregnated (corpus ha?morrhagicum) than when im- pregnation has taken place. In the latter ease the productive inflammation is more marked, and is accompanied by a fatty degeneration of the older granulations which gives them a yel- lowish tinge (corpus luteum\ In the centre of this yellow i-h zone is the remainder of the clot, and about it- periphery an envelope of fibrous tissue, which is usually irregular in contour. The corpus luteum finally becomes a mass of cicatricial ti—ue of greater size than that resulting from a corpus ha?morrhagicum (corpus album) (Figs. 1>7 and 18>). Fio. 1ST. tJii e Section from rabbit's ovary, illustrating the formation of the corpus luteum. tSobotta.l Recently ruptured Graafian follicle. Jtf, germinal epithelium; beneath it, the ovarian stroma. Bounding the follicle externally is the fibrous capsule of the follicle. Within this, thi, is a layer of proliferating fibrous tissue, composed of polyhedral cells with round nuclei. Among these are elongated nuclei belonging to endothelial cells springing from the capillaries, and destined to form the walls of future bloodvessels: e, epithelium of Uie membraua granulosa. Within this are the viscid remains of the liquor foIliouU, containing a few red Mood-corpuscles and some epithelial cells detached from the mem- brana granulosa, o/, red blood-corpuscles. This section was prepared from an ovary about twenty-four hours after eoitu», and the development of the layer thi probably took place within that time. 2. The Fallopian Tube. — The free surface of the Fallopian tube is covered by a serous membrane, continuous with the rest of the peritoneum. This rests upon fibrous tissue, in which the longi- tudinal bundles of smooth muscular tissue constituting the external THE REPRODUCTIVE ORGANS. 211 Fig. Iks. •■v^>-4v;*':.:v-7^' 1 : 1 -"v , r-'' , y'\^-.. • •.•■•■■■•.■••.« - » Section of young corpus luteuro, four days after coitus. The proliferating connective tissue has nearly filled the cavity of the follicle, only a small mass of fibrin remaining in its centre. The young connective tissue is highly vascularized, the blood in some of the capillaries being represented, £ ■- i^.^ - r (^<% ,-,■0® W •» &.&. '■.!'■' v*' '..- 1 .*;/&> r, Interstitial tissue in the testis of the cat. (Plato.) Three bloodvessels are shown in either complete or partial section. Portions of two seminiferous tubules are represented at the upper corners. Between these structures is the interstitial tissue, containing large cyto- plasmic cells. This tissue is rather more abundant in this instance than in the human subject. Each seminiferous tube is provided with a basement-membrane, upon the inner surface of which are epithelial cells. These are di- visible into three groups : first, a parietal layer of cells, the " sper- matogonia," lying next to the basement-membrane; second, a layer of cells, often two or three deep, called the " spermatocytes," lying upon and derived from the spermatogonia ; third, the "spermatids," lying most centrally. The spermatids are derived from the spermato- cytes, and are the elements from which the spermatozoa develop, one spermatozoon being formed from each spermatid. The cells of the parietal layer, that containing the spermatogonia, are not all alike. At intervals certain cells, called " sustentacular " 228 NORMAL HISTOLOGY. cells, or the "cells of Sertoli," are differentiated from the others (Figs. 201-213). These sustentacular cells rest with a broad base, the Fig. 201. Superficial aspect of the parietal cells of the seminiferous tube: rat. (Ebner.) /.basal plates of the sustentacular cells (cells of Sertoli), each containing a large vesicular nucleus, poor in chromatin, ami a distinct nucleolus of considerable size; v, spermato- gonia resting upon the basal plates of the cells of Sertoli. Only a few of the spermato- gonia are represented. Fig. 20'J. Fig. 203. II h 14 Mil / Sections from the testis of the rat, illustrating spermatogenesis. (Ebner.) Figs. 202-213.— in, spermatogonia; /, sustentacular cells, or cells of Sertoli ; h, spermatocytes; e, spermatids ; tsp, spermatids becoming transformed into spermatozoa: iv\ to wjIO traces the history of the spermatogonia from the resting condition to that in which they have grown to become primary spermatocytes. During this process they move from the parietal layer into that covering it. All, a recently formed spermatocyte ; M2 to A2o, growth of the spermatocyte; A.21, beginning of the division to form secondary spermatocytes; A22, its end; A23, secondary spermatocyte, with chromatin in open spfrein ; A2.I, division of the secondary spermatocyte to form two spermatids; s2fv, recently formed spermatid : . u 2f> to s'2'X growth of the spermatid. (By this time the preceding crop of spermatozoa is fully developed and has been discharged into the lumen of the seminiferous tube.) s30 and s31, beginning transformation of the spermatids into spermatozoa. Their cytoplasm blends with Unit of ilie sustentacular cell. .sp32 to h-p'.W, stages in the differentiation of the spermatozoa ; -III, completed spermatozoon ready to pass into the lumen of the tube. tpf (Fig. 212) and wll (Fig. 21;'.) illustrate the division of the spermatogonia before they begin to develop into spermatocytes. It is supposed that the sustentacular cells aid in the nourishment of the spermatids during their transformation into spermatozoa, and that after ihc discharge of the latter the cytoplasmic process is retracted toward the base- ment-membrane, bringing with it the globules of fat and cytoplasmic fragments of the spermatids represented by dark spots and small round bodies in nearly all the figures. This retraction is taking place at/, Fig. 201. The cells of Sertoli do not appear to mul- tiply ; at least no karyokinetic figures have been observed in their nuclei. THE REPRODUCTIVE ORGANS. 229 Fig. 204. Fig. 205. &&> ^om^t -*s -A 17 m i 16 Fig. 207. A 19 w w7 f Fig. 209. 5 -sp 35 UA21 ' 20-^3^i/^\ £ mm % ■ " m^ / iv X te 230 NORMAL HISTOLOGY. Fig. 210. Fig. 211. A 22 Ay r\ ■■'W> itmw I s26 w w 10 / Fig. 213. i iliii II; umk : J > loll / _2££b THE REPRODVCTIVF OliOAXS. 231 Fig. 2U. ''basal plate," directly upon the basement-membrane, where the edges of the basal plates are in e< intact, forming a sort of bed with depressions in its upper surface, in which the spermatogonia find lodgement. The cells of Sertoli possess a thick cytoplasmic process, which extends toward the lumen of the tubule, and to which those spermatids which are developing into spermatozoa become attached. For this reason they are called sustentaeular cells. Their nuclei differ from those of the neighboring spermato- gonia in being less rich in chromatin and in possessing a single and prominent nu- cleolus. The appearances of the various cells enumerated depend upon the stage in their activity which happens to be under observation. The general course of de- velopment, ending in the formation of the spermatozoa, is as follows : the spermatogonia, between the cells of Ser- toli, multiply until quite a collection of such cells is produced. Each division is followed by a period of rest, during which the chromatin increases in amount. When the final stage of rest is at an end and the cells have attained their maturity, they constitute what are called the primary spermatocytes. These now divide, each forming two secondary spermatocytes, which in turn divide, without an inter- mediate di.-tinct resting-stage, to form two spermatids. Each primary spermato- cyte, therefore, gives rise to four sperm- atids. It is during the division of the secondary spermatocytes that the redue- tail of flageiia; <•. end-piece. , . ' . . , . , The thickness of d may be tion m chromatin, winch \v:i- mentioned. „ illsr t0 the presence of a above, takes place lEi^'S. 202-2 1-'V<. Each sheath surrounding the actual . . flagella, which projects from sjiermatid receives, in addition to its por- t he sheath at c. tion of chromatin, a Miigle eentro.-ome. The .-pcrinatozoon, then, is derived from a corpuscle, the spermatid, which contain-; all the c— ontial organs of a cell, differing from the gen- eral cells of the body, the M>matie cells, only in pos>e— ing half the Human spermatozoa. (Bohniaud Davidoff, after Ketzius and Jensen.) The left figure repre- sents the side view and the middle figure surface-view of a spermatozoon. ,*, head (nu- cleus) : b, end-knob teentro- 232 NORMAL HISTOLOGY. usual number of chromosomes in its nucleus. It is unnecessary to pursue the chain of events through which the spermatid gives rise to the spermatozoon. It may suffice to state that the body of the latter consists of the chromatin of the nucleus ; that the long e ilium con- stituting the tail of the spermatozoon is developed from the cyto- plasm ; and that the centrosome of the spermatid is probably con- tained in the middle piece of the spermatozoon (Fig. 214). Even these conclusions are inferences from studies of spermatogenesis in the lower animals, and not from direct studies of that process in man. The latter undoubtedly conforms very closely to the former in all essential details. To return to the histology of the testis : the epithelial cells of the seminiferous tubules rest upon a basement-membrane, which is divis- Fig. 215. Basement-membrane from seminiferous tube of tbe rat. (KIhh.t,) m, endothelial cells com- posing the external layer ; I, cells, presumably leucocytes, intercalated 1 ictween the endo- thelial cells. The faint striations upon the endothelial cells represent wrinkles in the homogeneous membrane forming the inner surface of the basement-membrane; the wrinkling is probably due to a slight shrinkage of the endothelium. ible into two layers : first, an internal, extremely delicate, homoge- neous membrane, upon which the epithelial cells rest; and, second, a layer of endothelial cells (Fig. 215). The latter may bound, at least in places, the lymphatic spaces, which are abundant in the interstitial tissue of the testis. Toward the back of the testis the seminiferous tubules unite THE REPRODUCTIVE ORGANS. 233 with each other and open into a number of straight ducts of smaller diameter, called the " vasa recta." These are lined with a cubical epithelium resting upon an extension of the basement- membrane of the seminiferous tubes, and, in turn, open into a reticulum of tubules of larger diameter, situated in the mass of areolar tissue at the posterior aspect of the testis. This reticulum is called the " rete vasculosum," and the tubules composing it are lined with a low epithelium, apparently resting upon the surround- ing fibrous tissue, without an intermediate basement-membrane. These tubes permit an accumulation of semen before it enters the vasa efferentia. The vasa efferentia have a peculiar epithelial lining, which may be regarded as transitional between the cubical epithelium of the vasa recta and rete and the ciliated columnar variety lining the epididymis. It consists of alternating groups of cubical and ciliated columnar epithelial cells (Fig. 216). Fig. 216. Section of vasa efferentia from human testis. (Bohm and Davidoff.) a, cubical or secretory epithelium ; 6, columnar ciliated epithelium, with deeper pyramidal cells beneath those that bear the cilia. This form of ciliated epithelium corresponds to that found in the epididymis where the cubical epithelium is absent. The vasa efferentia, as already stated, open into the canal of the epididymis, through which their contents reach the vas deferens. The walls of the efferent tubes possess a layer of encircling smooth muscular fibres, which are reinforced in the epididymis by an addi- tional external layer of longitudinal fibres. The nerves supplied to the testis are destitute of ganglia, and are distributed to the vessels and surfaces of the seminiferous tubules. No terminations have been traced to the epithelial lining of those tubules. CHAPTER XVIII. THE CENTRAL NERVOUS SYSTEM. The functional part, or parenchyma, of the central nervous system is composed of ganglion-cells with their processes. Some of these processes are of cytoplasmic nature, and, as explained in the chapter on the elementary tissues, are called the protoplasmic processes. From each ganglion-cell at least one process is given off which differs from the protoplasmic processes, and is called the " axis-cylinder process." This in most cases becomes the axis- cylinder of a nerve-fibre, and may be invested with a medullary sheath and neurilemma at some point near or at some distance from its exit from the cell. It will be convenient, for the brief description of the central nervous system to which this chapter must be restricted, to adopt a special terminology for the different portions of the ganglion-cell and its processes, as follows : the term ganglion-cell will be restricted to the nucleus and the cytoplasm surrounding it ; the protoplasmic processes will be called the dendrites, and their terminations the teledendrites. The axis-cylinder process will be termed the neurite; the delicate branches it may give off in its course, the collaterals ; and the terminal filaments of the main trunk, col- lectively the teleneurites. The cell, with its processes and their terminations, will collectively constitute a neuron. A complete neuron, then, consists of (1) certain teledendrites, which unite to form one or more dendrites connecting them with the gan- glion-cell ; (2) the cell itself; and (3) one or more neurites, which may give oif collaterals and finally terminate in teleneurites (Fig. 217). At the present time these neurons are believed to be without actual connection with each other, but to convey nervous stimuli by contact. The course of the nervous impulses is from the teleden- drites to the nerve-cell, and thence, by way of the neurite, to the teleneurites, whence it is communicated, without a direct structural union, to the next tissue-element in the chain of nervous transmis- sion. Those neurites which carry stimuli from the nerve-centres 234 THE CENTRAL XERVOUS SYSTEM. 235 to the periphery, centrifugal impulses, form the axis-cylinders of some of the nerves. The axis-cylinders of those nerves which convey impulses from the periphery toward the nervous centres, Fig. 217. Sketch illustrating the composition of neurons. I, a neuron transmitting centrifugal impulses. II, a neuron receiving and transmitting centripetal impulses. Ill, a neuron, the function of which is supposed to be the distribution of impulses within the nerve- centre in which it is situated, a, ganglion-cell ; b, dendrite ; c, teledendrites ; d, neurite ; e, collaterals ; /, teleneurites. In II the body c represents some sensory organ imparting nervous impulses to the teledendrites of a sensory nerve. The nervous filament g is a neurite, presumably derived from the sympathetic nervous system, leading to teleneu- rites applied to a ganglion-cell, a, of a posterior spinal ganglion. The portion h of the "nerve" springing from that cell is regarded as a portion of the cell itself. In the embryonic condition the dendrite and neurite both spring directly and separately from the body of the cell, the portion k being a subsequent development, i, endothelial envelope surrounding the ganglion-cell. Ill represents a ganglion-cell, apparently devoid of distinct dendrites, but having numerous processes that at first appear protoplasmic, but soon assume the characters of neurites. These cells are found in the retina and olfactory bulb, and have been termed spongioblasts, cellulas amacrinas, and parareticu- lar cells. It is thought that nervous stimuli are received directly by the cytoplasm of the cell, without the intermediation of dendrites, j represents the omission of a portion of a fibre. The arrows indicate the directions taken by nervous impulses. centripetal stimuli, may be the dendrites connected with ganglion- cells in or near those centres ; e. //., in the posterior root-ganglia of the spinal nerves, or they may be the neurites springing from 236 NORMAL HISTOLOGY. peripheral ganglion-cells, as is exemplified in many, if not all, of the organs of special sense. I. THE SPINAL CORD. The axis of the spinal cord is composed of a column of gray matter containing numerous ganglion-cells and nervous filaments held in position by a cement-substance, neuroglia-cells, the fibrous prolongation of the ependyma cells lining the central canal, and a little fibrous tissue accompanying the vessels derived from the pia mater. Fig. 218. Pigs. 218 and 21!i.— Transverse sections of human spinal ford. (Sclwfer.) Fig. 218, from the lower cervical repi. .n ; Fig. 219, from the middle dorsal region, a, b, c, groups of ganglion-cells in the anterior horn ; d, cells of the lateral horn ; e, middle group of cells ; /, cells of Clarke's column ; g, cells of posterior horn ; c, c, central canal ; a, c, an- terior commissure of white matter. THE CENTRAL NERVOUS SYSTEM. 237 Fir,. 220 ^<$$ TTT/ 7 "^ /"^"V POSTERIOR / ,'V?^. f^W 1 R00T c* \Ua|f ''^^' ^Jy.ffi-^^" ;antero-!\ cfe^' ./( ; «'C1 ! LATERAL J \ §spi fes!°13p m | V'' ■*<,.."■ V*>^ vASCENDlNC^l '•■ r: 1^5$ ill fe ,;r -""'" :; ". ^£p^ N . ' V ~'^v ' ' /^vl ^'■■Y ■'■'■ : ' *y\'Cw*^&S^~ \i :■ : X\y. : . lili?il i ui/ -■ *■ \ v*'*Jiv^^ ' Pi! • ; ) \'KWM ■I V - '- "^> Psjf' ^s ajHI z ii§ll // V> ' ' ^^ 1 / i ^ i ! irYTO^i?-^' \ /o/ I \\\ WV\ i *\v 1 \\W\v w (f ^^^./ANTERIOR ~^QC P I JO \^P^V*0 ROOT-BUNDLES Transverse section of human spinal cord, from the middle lumbar region. (Schafer.) a b, c, groups of ganglion-cells in the anterior horn ; d, cells of the lateral horn ; i', middle group of cells ; /, cells of Clarke's column ; g, cells of posterior horn ; c. c, central canal ; a, c, anterior commissure of white matter. In cross-section this column of gray matter presents a transverse central portion, the gray commissure, near the middle of which is the central canal. At each side this gray commissure blends with masses of gray matter, occupying nearly the centre of each lateral half of the cord and having a general crescentic form. The ends of these crescentic masses form the anterior and posterior cornua of the gray matter, from which the anterior and posterior roots of the spinal nerves proceed. The anterior cornua are larger than the posterior and contain larger ganglion-cells. Surrounding the column of gray matter everywhere, except at the bottom of the posterior median fissure of the cord, and the interruptions formed by the nerve-roots in their exit from the gray matter, is a layer of white matter, formed of medullated nerve- fibres running parallel with the axis of the cord and held together by neuroglia and delicate vascularized fibrous bands proceeding from the deep surface of the pia mater. The white matter of the cord has been divided into a number of columns, for the most part indistinguishable through structural dif- ferences, but each containing fibres that play similar functional rules. These columns, with their names, are indicated in Figs. 218, 219, and 220. The columns of Goll and Burdach, forming the posterior 238 NORMAL HISTOLOGY. column of the white matter, between the posterior cornua and the posterior median fissure, conduct, for the most part, centripetal impulses. Impulses having the same upward direction are also conveyed by the direct cerebellar tract and the tract of Gowers in the lateral column of the white matter. Centrifugal impulses, motor stimuli, are conveyed by the fibres in the direct pyramidal tract of the anterior column and by those of the crossed pyramidal Diagram of spinal cord, illustrating the associations of its various nervous elements. (R. y Cajal.) a, collateral from Goll's tract, entering into the formation of the posterior com- missure ; b, collateral to the posterior horn ; c, collateral to the formatio reticularis and the anterior horn ; d, posterior nerve neurite, with its collaterals ; e, collaterals from the lateral column ; /, collaterals to the anterior commissure ; g, central canal ; ft, neurite in the crossed pyramidal tract from the commissure-cell of the opposite side ; i, its course in the commissure ; j, neurite from a large motor cell in the anterior horn I: ; ?, cell of the anterior horn, giving off a neurite dividing into an ascending and a descending branch (compare Fig. 224, D) ; m, commissure-cell ; n, cell giving off a collateral within the gray matter ; o, neurite of the cell u, in Clarke's column ; p, neurite from the mar- ginal cell .9, of the substance of Rolando ; q, cross-section of an axis-cylinder (neurite) in the white substance of the cord ; r, division of a posterior nerve-fibre (neurite) into ascending and descending branches; t, small cell in the substance of Rolando. Aside from the cells indicated in the figure, the gray matter contains some that give off neurites which divide into two or three branches while in the gray matter, the branches going to different columns of white matter. There are also cells with very short neurites, which terminate in teleneurites within the gray matter, and probably distribute nervous impulses for short longitudinal distances. tract in the lateral column. The tracts hitherto considered contain fibres that are continued into the higher nerve-centres of the brain and cerebellum, to or from which they convey nervous impulses. But the spinal cord is not merely a collection of such transmitting THE CENTRAL NERVOUS SYSTEM. 239 fibres. It is also a nerve-centre of complex constitution, in which neurons terminate in teleneurites or arise in teledendrites. Some of the neurons within the cord are confined to its substance, and constitute nervous connections between the different parts at various levels. These may be termed longitudinal commissural neurons, or association-fibres. Portions of such neurons are repre- sented in the diagram of a cross-section of the cord (Fig. 221), which also contains representations of some of the neuriies in the posterior spinal nerve-roots, with their collaterals ending in tele- neurites within the gray matter {<(). On the right side of the figure, the nerve-cells, with their dendrites and the beginning of the neu- rites, are shown. On the left side the neuriies connected with cells at another level are shown, re-entering the gray matter, where they terminate in teleneurites. In studying this figure it must be borne in mind that the teledendrites of the neurons on the right are in close relations with the teleneurites of other neurons, and that the teleneurites represented on the left are in close relations with the teledendrites of other neurons. These association-neurons are, therefore, merely links in chains of communicating neurons. They are again represented in Fig. 224, D and E. Aside from these association-neurites, the gray matter of the cord receives innumerable collaterals from the neurites forming the axis-cylinders of the nerves in the various columns of the white matter. These collaterals terminate in teleneurites, which are in close relations with the teledendrites of the neurons arising in the cord. The distribution of these collaterals is represented in Fig. 222. The collaterals from the anterior column enter the anterior horn of the gray matter, where they are chiefly distributed about the large ganglion-cells in the antcro-lateral portion of its substance (Fig. 218, b ; Fig. 221, J), but may also extend to other parts of the gray matter. The collaterals from the fibres in the lateral columns of the white matter are most numerous near the pos- terior horn, which they enter, many of them passing through the gray matter behind the central canal and forming a part of the posterior or grav commissure of the cord (Fig. 222, I). The col- laterals from the posterior column are divisible into four groups . first, those which arc given off in the lateral portion of that column (Fig. 222, ({), and are distributed in the outer portion of the pos- terior horn and in the substance of Rolando (Fig. 222, I) ; second, those which end in Clarke's column (Fig. 222, J); third, those 240 NORMAL HISTOLOdY. which arise chiefly in the column of (Joll, pass through the sub- stance of Rolando, and then form an expanding bundle distributed in the anterior horn of the gray matter, where they are in associa- tion with the dendrites of the motor cells in that region (these fibres form the reflex bundle of Kolliker, Fig. 222, H) ; fourth, collaterals springing from fibres in the posterior column, passing Cross-section of the spinal cord of a newborn child, showing the distribution within the gray matter of the collaterals from the neurites of the white matter. (R. y Oajal.) a. anterior fissure; B, pericellular branches of the collaterals from the anterior column ; c, collaterals of the anterior commissure; D, posterior bundle of collaterals in the posterior commis- sure ; E, middle bundle of the posterior commissure ; /, anterior bundle ; G, collaterals from the posterior column ; H, senso-motory collaterals from the posterior column ; I, pericellular terminations of collaterals in the posterior horn ; J, collateral terminations in the column of Clarke. through the posterior commissure of gray matter and ending in the substance of Rolando of the opposite side (Fig. 222, D). The reflex collaterals arising in the posterior column are shown in Fig. 223, where their teleneurites are in close relations with the teledendrites of the motor cells c. The centripetal or sensory neurites of the posterior spinal nerve- roots spring from the ganglion-cells of the spinal ganglia. When they have entered the white matter of the spinal cord they divide the ci:sn;.[L SEin-ous system. 241 into two branches (Fig. '22 \ , r). One of those- ascends in the white substance and the other descends. Both branches give off numer- ous collaterals, which penetrate the gray matter, ending in teleneu- rites associated with the teledendritcs of the cells in both the ante- rior and the posterior horns, and the column of Clarke. The main branches of the sensory neurite also enter the irrav matter, after Fib. m Km. 2-2-t. Fig. 2;;!.— Diagram of the senso-motory reflex collaterals in the cord. (R. y CajaU n. gan- glion-cell of the posterior nerve-root : 6, division of its nenrite into ascending and de- scending branches : e. collaterals to anterior horn: rf, terminal teleneurites in the pos- terior horn ; c, motor cell of the anterior horn, with its processes. Fig >-l — longitudinal section of a part of the spinal cord, including a posterior nerve-root. Semidiagrauiuiatic. (R. y Cajal \ A, posterior nerve-root: S. white substance of the cord ; O, gray matter: JS, collateral teleneurites in the gray matter; 0. cell with a single ascending neurite ; />. cell with bifurcating neurite. terminating at /"and J; E t cell with a simile descending neurite: F, O, terminal teleneurites ; a', collateral from a branch of the posterior root neurite ; 6', collateral from the main neurite before its bifurcation. following the posterior column for a short distance, anil end in tele- neurites aniono- the cells of the posterior horn and the substance of Rolando. The collaterals which pass to the anterior horns (Fig. '222, H. and Fio-. 2'2^. c) have to do with the origin of reflex een- ir, 242 NORMAL HISTOLOGY. trifugal impulses emanating from the motor cells in that region (Fig. 223, e, and Fig. 221, j). The further transmission of these centripetal stimuli toward the higher nerve-centres of the brain probably takes place : first, through the cells in the posterior horns, the neurites from which pass into the lateral columns and there ascend the cord ; second, through the cells of Clarke's column, which also send neurites into the lateral column, where they enter the direct cerebellar tract (Fig. 221, o ; see also Fig. 224). In addition to these centripetal or sensory neurites, the posterior nerve- roots contain a few centrifugal neurites. Fig. 225. Diagram of a sensory and a motor tract. (R. y Oijal.) A, psycho-motor region in cerebral cortex ; B, spinal cord ; C, voluntary muscle ; D, spinal ganglion ; £>', skin ; a, axis-cylin- der of a neuron extending from the cerebral cortex to the anterior horn of the spinal cord, where the terminal teleneurites are in relations with the teledendrites of the motor cell at b. The sensory stimulus arising in the skin, D\ is transmitted by the neuron dDce to /, where it is communicated to the neuron fg. The point / may be in the cord or in the medulla oblongata. In order to understand the origin of the anterior spinal nerve- roots Ave must first consider the course of the centrifugal neurites in the pyramidal tracts (Figs. 218, 219, 220). These enter the gray matter and end in teleneurites, which are associated with the tele- THE CENTRAL NERVOUS SYSTEM. 243 dendrites of the cells in the anterior horn, especially those which give oft' neurites to the anterior roots of the spinal nerves (Fig. 221, j). The foregoing details may be summarized by means of the accom- panying diagram (Fig. 225), in which the course of a nervous stim- ulus is traced from the organ of sense in, e. g., the skin, to the cortex of the cerebrum, where it is translated into a nervous im- pulse, the course of which is traced to the motor plates of the vol- untary muscles. The reflex mechanism which might at the same time be set into operation is not represented in the diagram, but will be sufficiently obvious from an inspection of Fig. 223. It will be noticed in Fig. 225 that both the sensory stimulus and the motor impulse are obliged to pass through at least two neurons before they reach the ends of their journeys. But the nervous currents are by no means entirely confined to the course marked by the arrows. Impulses may be transmitted in an incalculable number of delicate tracts through the collaterals given off from the neurites within the central nervous system, some of which are indicated in the diagram, and all of which end in teleneurites associated with the teledendrites of, perhaps, several neurons. One of these collateral tracts has already been considered, namely the senso-motory reflexes illus- trated in Fig. 223. II. THE CEREBELLUM. The cerebellum is subdivided into a number of laminae by deep primary and shallow secondary fissures. The gray matter of the organ occupies the surfaces of these laminae, while their central por- tions are composed of white matter. The gray matter may be divided into two layers: an external or superficial "molecular layer" and an inner "granular layer" (Figs. 226 and 227). The molecular layer contains two forms of nerve-cells : first, the large cells of Purkinje ; second, small stellate cells. The cells of Purkinje have large, oval, or pear-shaped bodies lying at the deep margin of the molecular layer. Their dendrites form an intricate arborescent system of branches extending peripherally to the surface of the gray matter, and give off innumerable small teledendrites throughout their course. All these branches lie in one place, perpendicular to the long axis of the lamina in which they are situated, and the teledendrites come into relations with certain longitudinal neurites springing from the cells of the granular layer, 1244 NORMAL HISTOLOGY. to be presently described. The neurites of the cells of Purkmje extend through the granular layer into the white matter and soon acquire medullary sheaths (Fig. 226, o) ; but before they leave the granular layer they give off collaterals, which re-ascend into the molecular layer, where their teleneurites are in relations with the Fig. 226. Section of a cerebellar lamina perpendicular to its axis. :R. y Cajal.) .1, molecular layer of the gray matter; B, granular layer; C, white substance; a, cell of Purkinje; o, its neurite, giving off two recurrent collaterals ; b, b, stellate cells of the molecular layer; rf, basket-like distribution of the teleneurites of one of their collaterals around the body of a cell of Purkinje ; e, superficial stellate cell, which does not appear to come into rela- tions with the bodies of the cells of Purkinje, but must lie close to their dendrites ; /, large stellate cell of the granular layer; g, small stellate cell of the granular layer; h, centripetal neurite of a " moss " fibre ; n, centripetal neurite distributed in the molecular layer; j, m, neuroglia-cells. The arborescent dendrites of only one of the cells of Pur- kinje are represented in the figure. Were those of the neighboring cells also represented, the molecular layer of the gray matter would display an enormously complex interdigi- tation of such filaments. teledendrites of neighboring cells of Purkinje. These collaterals are believed to occasion a certain co-ordination in the action of those cells of Purkinje which are near each other. The stellate cells of the molecular layer (Fig. 226, b, e) pos- THE CEXTn.iL NERVOUS SYSTEM. 245 sess neurites, which lie in the same plane with the arborescent dendrites of the cells of Purkinje, and send collaterals to end in a basket-work of teleneurites applied to the bodies of the cells of Purkinje. The terminal teleneurites of these stellate cells also end in the same situation. Other smaller collaterals extend toward the surface of the cerebellar lamina. The granular layer of the gray matter also contains two varieties of nerve-cells : the " small stellate cells," which are most numerous, and the "large stellate cells." Fig. 227. Section of a cerebellar lamina parallel to its axis. (R. y Cajal.) A, molecular layer of the gray matter ; B, granular layer ; C, "white substance ; a, small stellate cell of the granular layer, from which a neurite enters the molecular layer, where it bifurcates, sending branches throughout the length of the lamina; b, bifurcation of one of these neurites; c , slightly bulbous termination of one of the neuritic branches ; d, body of a cell of Pur- kinje seen in profile ; /, neurite of a cell of Purkinje. The small stellate cells (Fig. 22(3, g, and Fig. 227, a) are scat- tered throughout the granular layer, and it is owing to the abun- dance of their nuclei that this layer has received that name. Their dendrites are few in number and short, but their neurites are very long. They extend perpendicularly into the molecular layer, where they bifurcate, the branches lying parallel with the axis of the cerebellar lamina and its surface. These fibres appear to run the whole length of the lamina, and to come in contact with the tele- dendrites of the cells of Purkinje, to the planes of which they run perpendicularly. They are thought to coordinate the action of a long series of the cells of Purkinje. 246 NORMAL HISTOLOGY. The large stellate cells of the granular layer lie near its external margin, whence they send their dendrites into a large area of the molecular layer, while their neurites are distributed in the granular layer, where they must come into relations with the dendrites of the small stellate cells (Fig. 226,/). The distribution of the cells and their processes in the cerebellum indicates a very complex interchange of nervous impulses and an extraordinary coordination in the action of the various neurons. This complication is still further increased by the presence of centripetal neurites, which enter the cerebellum through the white matter and ai-e distributed in the gray matter. These are of two sorts : first, neurites which penetrate the granular layer and are distributed among the proximal dendrites of the cells of Purkinje (Fig. 226, n) ; second, neurites, called " moss " fibres, which are dis- tributed among the cells of the granular layer. The teleneurites of these fibres have a mossy appearance, whence the name (Fig. 226, h). The origin of these centripetal neurites is not known, but it is sur- mised that the " moss " fibres may enter the cerebellum through the direct cerebellar tracts of the cord. III. THE CEREBRUM. The gray matter of the cerebral cortex has been divided into four layers : first, an external molecular layer ; second, the layer of small pyramidal cells; third, the layer of large pyramidal cells; and, fourth, an internal layer of irregular or stellate cells. Of these layers, the second and third are not clearly distinguishable from each other (Fig. 228). The molecular layer contains three sorts of nerve-cells, two of which are closely related to each other, differing only in the form of the cell-bodies, which are small in both varieties (Fig. 229, J, B, and C) ■ while the cell-bodies of the third variety are large and polygonal (Fig. 229, X>). The small cells (A, B, C, Fig. 229) pos- sess two or three tapering processes, which at first resemble proto- plasmic processes, but soon assume the characters of neurites or axis- cylinders. These neurons, then, resemble the type depicted in Fig. 217, III. Their neurites run parallel to the surface of the convo- lution in which they are situated, sending off numerous perpen- dicular collaterals, and finally end in teleneurites within the molec- ular layer. The collateral and terminal teleneurites are probably in relations with the dendrites of the pyramidal cells of the under- THE CENTRAL NERVOUS SYSTEM. 247 Fig. 228. lying layers, which form arborescent expansions in the molecular layer, similar to those of the cells of Purkinje in the cerebellum, extending to the surface of the gray matter. The large stellate cells of the molecular layer (Fig. 229, D) send their dendrites in various directions into the molecular layer and the layer of small pyramidal cells lying beneath it. The neurite is distributed in the molec- ular and upper portions of the under- lying layers, but is never extended into the white matter. The dendrites of these cells come into relations with the neurites of the other cells of this layer and with those that proceed upward from some of the cells in the deeper layers. The small spindle- and stellate cells (A, B, C, Fig. 229) are considered to be the autochthonous cells of the cerebral cortex — i. e., the cells of the brain in which the highest order of nervous im- pulses find their origin. The small spindle-shaped cells, with their peculiar neurites, are extremely abundant and fill the molecular layer with a mass of interwoven filaments. The second and third layers of the cerebral gray matter are characterized by the presence of pyramidal nerve- cells of various sizes, the smaller being relatively more abundant in the second layer and the larger in the third layer. From the apex of the pyram- idal cell a stout, " primordial " dendrite passes vertically into the molecular layer, where, as well as during its course to the molecular layer, it gives off numerous branches, and finally ends in a brush of teledendrites extending to the surface of the gray matter (Fig. 230, A , B). Other and shorter dendrites are given off from the body of the cell, which ramify and end in the second, third, or fourth layer of the gray matter. The neurites from the bases of the pyramidal cells pass vertically downward into the white substance, where they may bifurcate, giving axis-cylinders to two nerve-fibres. While within ^s Vertical section of the cerebral cor- tex, showing its layers. (R. y Cajal.) 1, molecular layer ; %, layer of the small pyramidal cells ; 3, layer of the large pyram- idal cells ; U, layer of polymor-- phic cells ; 5, white matter. 248 NORMAL HISTOLOGY. Fig. 229. Cells of the molecular layer of the cerebral cortex. (E. y Cajal.) A, C, small spindle-shaped cells ; B, small stellate cell ; D, large stellate cell. The branches marked c are neuntes. Fig. 230. Fig. 231. Fig. 230.— Diagrammatic section through the cerebral cortex. (R. y Cajal.) A, small pyram- idal cell in the second layer ; B, two large pyramidal cells in the third layer ; C, B, poly- morphic cells in the fourth layer : E, centripetal neurite from distant nerve-centres ; F, collaterals from the "white substance ; G, bifurcation of a neurite in the white sub- stance. The arrows indicate the centripetal and centrifugal courses of nerve-impulses, but it is probable that centripetal impulses have to pass through other neurons (perhaps the spindle-cells of the molecular layer) before they are translated into centrifugal im- pulses. Fig. 231.— Cells with short neurites in the cerebral cortex. (E. y Cajal.) A, molecular layer ; B, white substance ; a, cells with neurites, which speedily divide into numerous tele- neurites in the neighborhood of the cell belonging to the same neuron ; ft, cell with a neurite extending vertically toward, but not entering, the molecular layer ; c, cell with a neurite distributed within the molecular layer ; d, small pyramidal cell. THE CENTRAL NERVOUS SYSTEM. 249 the gray matter, and after their entrance into the white matter, these neurites give off collaterals, which branch and end in terminal bulbous expansions without breaking up into a set of teleneurites. The irregular cells of the fourth layer (Fig. 230, C, D) do not send their dendrites into the molecular layer, but distribute them within the deeper layers of the gray matter. Their neurities, like those of the pyramidal cells, enter the white matter, where they may or may not bifurcate. Besides the cells in the deeper layers of the gray matter hitherto described, those layers contain cells with short neurites, which are divisible into two classes : first, spindle-shaped or stellate cells, sending their neurites into the molecular layer (Fig. 231, c) or into the second layer of the gray matter (Fig. 231, b) ; second, poly- morphic cells with radiating dendrites and copiously branching neurites, both of which are distributed within a short distance of the cell. These cells are believed to distribute nervous impulses to the neurons in their vicinity. The gray matter of the cortex also receives centripetal neurites from the white matter, which give off numerous collaterals and ter- minate in the molecular layer. The white matter of the cerebrum contains fibres that may be divided into four groups : first, centrifugal or "projection" fibres; second, " commissure-fibres," which bring the two sides of the brain into coordination (these lie in the corpus callosum and in the ante- rior commissure); third, "association-fibres," which coordinate the different regions of the cerebral cortex on the same side ; fourth, centripetal fibres, reaching the cortex from the peripheral nervous system or cord. The centrifugal or projection-fibres arise from all parts of the cortex, springing from the pyramidal and, perhaps, also from the irregular cells. Many of these fibres give off a collateral, which passes into the corpus callosum, to be distributed in the cortex of the opposite side, commissural collaterals, and then pass on to the corpus striatum, to the gray matter of which further collaterals may be given off, after which the main neurite probably passes into the pyramidal tracts of the cord through the cerebral cms (Fig. 232, a). The commissure-fibres (Fig. 232, b, c) also arise from the pyram- idal cells of the cortex, mostly from the smaller variety, and pass into the corpus callosum or the anterior commissure, to be dis- 250 NORMAL HISTOLOGY. tributed in the gray matter of the cortex of the opposite hemisphere, but not necessarily to the corresponding region. These commissural Fig. 232. Centrifugal and commissural fibres of the cerebrum. (R. y Cajal.) ^.corpus callosum; B, anterior commissure ; C, pyramidal tract ; a, large pyramidal cell, with a neurite sending a large collateral into the corpus callosum and then entering the pyramidal tract. Between a and & is a second similar cell, the neurite from which contributes no branch to the corpus callosum. 6, small pyramidal cell giving rise to a commissural neurite ; c, a similar cell, the neurite of which divides into a commissural and an association branch ; d, collateral entering the gray matter of the opposite hemisphere ; e, terminal teleneu- rites of a commissural fibre. fibres give off collaterals, which also end in the gray matter, and are accompanied by collaterals from the centrifugal fibres, which likewise end in, and send collaterals to, the gray matter. Fig. 233. Association-fibres of the cerebrum. (E. y Cajal.) The figure represents, diagrammatically, a sagittal section through one of the cerebral hemispheres, a, pyramidal cell, with neu- rite giving off collaterals to, and ending in, the gray matter of the same side ; b, a similar cell ; c, cell with a branching neurite passing to different parts of the hemisphere ; d, teleneurites ; e, terminal collateral twigs. The origin, course, and general distribution of the association- fibres are indicated in Fig. 233. They are so numerous that they THE CENTRAL NERVOUS SYSTEM. 251 form the great bulk of the white substance, where they are inex- tricably interwoven with the other fibres there present. Besides the centripetal neurites of the association and commissural neurons, their collaterals and those of the projection-fibres, the gray matter of the cortex receives terminal neurites from larger fibres that are probably derived from the cerebellum and cord (Fig. 230, E ). These give off numerous collaterals and teleneurites, which are distributed to the small pyramidal cells of the second layer, and probably also penetrate into the molecular layer, where they end in numerous teleneurites among the cells of that layer. In the diagrammatic figure 230 the probable course of nervous stimuli to and from the cerebral cortex is indicated. The possi- bilities of transmission within a structure of such marvellous com- plexity are incalculable. The above structural details of the central nervous system are chiefly taken from the publications of Ramon y Cajal. They are the result of researches carried on by the application of the methods devised by Golgi to the nervous structures of the lower vertebrates and embryos. Such details cannot be observed when specimens have been hardened and stained by methods used for the study of other structures. In such specimens the nuclei of the nerve-cells and those of the neuroglia are stained and become prominent. But the multitude of nervous filaments lying between the cells and the processes of the neuroglia-cells are not differentiated, but appear as an indefinite, finely granular material, in which the cell-bodies apparentlv lie. Where the cells are sparse or small, as in the first layer of the cerebral gray matter, the tissue appears finely molecu- lar. Where the cells are numerous but small, their stained nuclei give the tissue a granular appearance, as, for example, in the second layer of the cerebellar cortex. The brain and spinal cord are invested by a membrane of areolar tissue, called the "pia mater." Extensions of this areolar tissue penetrate the substance of the cord and brain, giving support to bloodvessels and their accompanying lymphatics. This areolar tissue also extends into the ventricles of the brain, where it receives an external covering of epithelium continuous with that lining the ventricles, which is ciliated. Externally, the areolar tissue is con- densed to form a thin superficial layer. CHAPTER XIX. THE ORGANS OF THE .SPECIAL SENSES. 1. Touch. — The ners'ous filaments distributed among the cells of stratified epithelium have already been depicted in Fig. 93. Similar filaments occur in the human epidermis, and it is probable that some of them are the teledendrites of spinal ganglion-cells, while others arc centrifugal teleneurites subserving the functions Fig. 234. Fig. 235. Tactile corpuscles. Fig. 234.-Meissner's corpuscle, from the human corium. (Bohm and Davidoff.) a, upper portion, in which the epithelial cells alone are represented. The nuclei of those cells are in the broader peripheral portion of the cytoplasm ; 6, nerve-dendrite coiled about the epithelial cells ; c, nerve-fibre. Fig. 235.— Krause's corpuscle, from the human conjunctiva. (Dogiel.) a, endothelial envelope; b, nucleus of connective-tissue cell within the fibrous capsule ; e, nerve-fibre. of nutrition, etc., or the teledendrons of neurons belonging to other than the spinal system of nerves. Besides these nervous terminations the skin possesses certain bodies, which are called "tactile corpuscles" and "Pacinian bodies." 252 THE ORG ASS OF THE SPECIAL SESSES. 253 These are situated in the coriuni, the former lying in some of the papillre projecting into the rete mucosum. The tactile corpuscles are of two forms, differing slightly from each other in structure : first, those of Meissner, and, second, those of Krause. The tactile corpuscles of Meissner (Fig. 234) consist of a group of epithelial cells closely associated with the teledendrites of a nerve-fibre. The cells are closely compacted together to form an ellipsoid bod)-. The nervous dendrite, with its medullary sheath, enters this body at one of its ends, and, after making one or two spiral turns around the mass of epithelial cells, loses its medullary sheath and breaks up into a number of teledendrons, which are dis- tributed among the epithelial cells. The neurilemma and the endoneurium of the fibre are continued over the corpuscle, consti- tuting a species of capsule. The tactile corpuscles of Krause (Fig. 235) possess a capsule composed of delicate fibrous tissue, covered and lined with endo- thelial cells. The dendrite of the nerve-fibre loses its medullary sheath upon penetrating this capsule, and then breaks up into tele- dendrites. that form a complex tangle within the cavity of the cor- puscle. There appear to be no cells among the teledendrites, the interstices being occupied by lymph. These corpuscles are espe- cially abundant in the conjunctivae and the edges of the eyelids, but occur also in the lip, large intestine, posterior surface of the epiglottis, and the glans penis and clitoris. They may receive dendrites from more than one nerve. Those of Meissner are found throughout the skin, being most abundant where the tactile sense is most acute. The Pacinian corpuscles (Fig. 236) are large oval bodies, com- posed of a number of concentric cellular lamellae, surrounding a central, almost cylindrical cavity, and covered externally with a layer of endothelioid cells, which appear to be continuous with the delicate endoneurium of the fibre. The latter enters the corpuscle at one of its ends, soon loses its medullary sheath, and is finally subdivided into a number of teledendrites within the central cavity. The "genital corpuscles" which are found in the glans of the penis and that of the clitoris are similar in structure to the Pacinian corpuscles, but the lamellar envelope of the latter is here reduced to one or two ill-developed lamella?. The nervous impulses inaugurated in the tactile and Pacinian i54 NORMAL HISTOLOGY. corpuscles are probably transmitted to the sensorium in the manner indicated in Fig. 225. Pacinian corpuscles are found in the palms and soles, on the nerves of the joints and periosteum, in the pericardium, and in the pancreas. 2. Taste. — The special organs of taste appear to be the taste- Fig. 236. Pacinian corpuscle, from the mesentery of the cat. (Klein.) a, nerve-fibre ; b, concentric capsule. The nature of the cells in this capsule is a matter of doubt ; analogy would suggest their epithelial nature. buds, situated in the walls of the sulci surrounding the circum- vallate papilla? of the tongue (see Fig. 109). The taste-buds are bulb-shaped groups of epithelial and nervous cells, situated within the stratified epithelium lining the sulci. The cells composing these buds are spindle-shaped or tapering, and their ends are grouped together at the base of the bud and converge at its apex, where they occupy a " pore " in the stratified epithelium. The epithelial cells do not appear to be active in the inauguration of nervous impulses, but the more spindle-shaped cells lying among them seem to be endowed with nervous functions. They may, pos- sibly, be regarded as peculiar neurons ; their distal processes, which receive stimuli at the pore, being the dendrite, while the proximal process is the neurite. The latter divides into a number of minute branches, which, from this point of view, might be regarded as tele- neurites. Be this as it may, these branches come into close relations THE ORGANS OF THE SPECIAL SENSES. 255 with the teledendrites of nerve-fibres supplied to the taste-bud (Fig. 237). The stratified epithelium surrounding the taste-buds, as elsewhere, contains teledendrites from sensory nerves. 3. Smell. — The olfactory organ occupies a small area at the top of the nasal vault, and extends for a short distance upon the sep- tum and external wall. Its exposed surface is about equal to that Fig. 237. Diagram of a taste-bud and its nervous supply. (Dogiel.) a, radicle of the gustatory nerve ; 6, radicle of a sensory nerve ; c, epithelial cell ; d. nerve-cell. The shaded part of the figure represents the stratified epithelium lining the sulcus of the circumvallate papilla. Only one of the epithelial or supporting cells of the upper bud is represented in the figure ; the others are omitted. The structure of the lower bud is not shown. ' of a five-cent piece. It is a modified portion of the mucous mem- brane of the nose, which may be divided into this, the olfactory portion, and the general or respiratory portion. The respiratory portion of the nasal mucous membrane is covered with a stratified, columnar, ciliated epithelium, with occasional mucigenous goblet-cells, resting upon a basement-membrane. Be- neath this is the membrana propria, resembling that of the small intestine in being rich in lymphadenoid tissue, which may, here and there, be condensed into solitary follicles. Beneath the membrana propria is a richly vascularized submucous areolar tissue, containing compound tubular glands, the glands of Bowman, which open upon the surface of the mucous membrane. These glands secrete both mucus and a serous fluid. In the olfactory region the columnar epithelial cells are devoid of cilia, but possess a thin cuticle, and the epithelium rests directly upon the lymphadenoid tissue, without the intermediation of a base- ment-membrane (Fig. 238). Between these epithelial cells are the 256 NORMAL HISTOLOGY. nervous cells, which constitute the receptive elements of the olfac- tory nervous tract. These are cells with large nuclei and cylin- drical distal bodies, which terminate at the surface of the epithelial layer in several delicate hairs projecting from the surface (Figs. 239 and 240). The proximal ends of the cells rapidly taper to a delicate Fig. 238. Bn . *. *, -' #* rr ~^' »» * »~ ,'#7 l'~ bb—.^ «,« a . *'. V • » »* • • » • i. :•'■ ••• * V , ■xt^ ' " v - ' ■ '*s(5J5*' /a' "#" ^' ''/ S. » \ v Vertical section through the olfactory mucous membrane of the human nose. (Brunn.) «, nuclei of the columnar epithelial cells ; re, nuclei of the nervous or olfactory cells lying among those of the epithelium ; 6:, nuclei of basal pyramidal epithelial cells lying among the branching proximal ends of the columnar epithelial cells and tapering ends of the nervous cells ; pz, pigmented cell in the layer of lymphadenoid tissues beneath the epithelium; Ba, duct of a gland of Bowman; Bb, dilated subepithelial portion of the duct, receiving several of the tubular acini, BL The connection between the duct and tubes is not shown, n, v, branches of the olfactory nerve ; re*, atypical nervous cell. filament, which extends through the subepithelial tissue and becomes associated with others to form the olfactory nerve. The distal ends of the nerve-cells represent the dendrites of neurons, the neurites of which form the axis-cylinders in the olfactory nerve. The neurites in the olfactory nerve pass through the cribriform plate of the ethmoid bono to the olfactory bulb of the brain, where THE ORGANS OF THE SPECIAL SENSES. Fig. 239. i,l 257 Epithelial layer of the human olfactory mucous membrane. (Brunn.) Isolated elements. Three epithelial cells, with forked proximal ends, are represented, together with a ner- vous cell bent out of position and the distal end of a second nervous cell. M.I, cuticle of the columnar epithelium, which is not continued over the end of the nervous cell. The cuticle of neighboring cells unites at the edges to form a species of membrane, which appears to be perforated for the exit of the distal ends of the nervous cells. A similar cuticle is found in the retina, where it has received the name " limiting membrane." Fig. 240. Vertical section of the epithelium, showing the arrangements of its elements. The nervous cells, with their neurites, are black. they terminate in teleneurites within little globular structures, called the "glomeruli of the bulb." 17 258 NORMAL HISTOLOGY. The olfactory bulb may be divided into five layers: first, the layer of peripheral nerves, containing the neurites of the olfactory nerve ; second, the layer containing the olfactory glomeruli ; third, the molecular layer ; fourth, the layer of the mitral cells ; fifth, the granular layer. The first layer is, as already stated, occupied by the neurites from the nervous cells in the olfactory mucous membrane. These neurites constitute the axis-cylinders of the olfactory nerve. The glomeruli of the second layer are small globular masses formed by the closely associated teleneurites of the olfactory nerves and teledendrites from the mitral cells of the fourth layer, the den- drites from which pass through the third or molecular layer. A few cells of neuroglial" nature may be associated with these nervous terminations, but the chief mass of each glomerulus is composed of interwoven teleneurites and teledendrites. The third, or molecular, layer contains small spindle-shaped nerve-cells, which send dendrites to the glomeruli of the second layer and neurites into the granular (fifth) layer, where they turn and take a centripetal direction toward the cerebrum. The fourth layer is characterized by the presence of large tri- angular nerve-cells, the mitral cells, the dendrites from which pass through the molecular layer, to end in teledendrites within the glomeruli. A single mitral cell sends dendrites to more than one glomerulus. The neurites from these cells pass, centripetally, to the olfactory centre of the cerebrum. The fifth, granular, layer contains the centripetal neurites of the mitral cells, and also centrifugal neurites from the cerebrum. The latter are distributed in teleneurites within the granular layer itself. This layer also contains small polygonal nerve-cells of two sorts : first, cells resembling those of the third type represented in Fig. 217, the processes from which are distributed in the granular and molecular layers. They are probably association-cells. Second, cells (Fig. 241) with dendrites in the granular layer and teleneurites in the molecular layer. These cells would distribute impulses re- ceived from the centrifugal fibres, which end in the granular layer, among the teledendrites in the molecular layer. The sense of smell, then, is aroused by stimulations of the distal ends of the nervous cells in the olfactory mucous membrane (Fig. 241), which are transmitted to the glomeruli where they leave the first neuron, being communicated to the second, represented by the THE ORGANS OF THE SPECIAL SENSES. 259 mitral cells and their processes, by which they are conveyed to the cerebral cortex. In its passage through this tract numerous collat- Fig. 241. Diagram of the nervous mechanism of the olfactory apparatus. (R. y Cajal.) a, olfactory portion of the nasal mucous membrane ; b t second or glomerular layer of the olfactory bulb j, at the right edge of the molecular layer, which is dotted. The cells of this layer are omitted, c, fourth layer of the bulb, the layer of the mitral cells, two of which are represented ; e, m, cells of the fifth or granular layer ; d, olfactory tract ; g, cerebral cor- tex; h, neurite from a mitral cell, giving off a collateral to the dendrites of a pyramidal cell in the gray matter of the brain ; /, pyramidal cells of the olfactory tract ; j, collateral from a mitral neurite passing, recurrently, into the molecular layer ; I, centrifugal neurite from the cerebrum. eral and association-tracts may be influenced in a manner too com- plicated to be readily followed. Fig. 242. Diagram of the distribution of the auditory nerve within the mucous membrane of the crista acustica. (Niemack.) The bodies of the hair-cells are dotted. Between them are the cells of Deiters, the nuclei of which are shown below the hair-cells. The nervous fila- ments are distributed between these cells. 4. Hearing. — The acoustic nervous apparatus resembles somewhat that which subserves the sense of touch. The receptive portion consists 260 NORMAL HISTOLOGY. of a layer of epithelium containing two sorts of cells : first, ciliated cells, which are somewhat flask-shaped and are called "hair-cells"; second, epithelial cells, the " cells of Deiters," which surround and enclose the hair-cells, except at their free ends, and reach the sur- face of the mucous membrane, where their ends are cuticularized. These cells of Deiters extend from the surface of the membrane to the basement-membrane, while the hair-cells extend only for a por- tion of that distance. The dendrites of the auditory nerve are distributed among these cells, but are not in organic union with them (Fig. 242). In this respect the auditory apparatus differs from the olfactory and resem- bles the tactile. The nervous dendrites are processes of bipolar ganglion-cells situated in the ganglia on the branches of the auditory nerve. The neurites from those cells presumably carry the nervous stimuli to the cerebrum. The bipolar cells are, therefore, analogous to the posterior root ganglion-cells of the spinal nerves. Whether this single neuron carries the nervous stimulus directly to the cere- bral cortex cannot be stated, but it is probable that there is an inter- mediate neuron in the tract of transmission, perhaps in the medulla oblongata. 5. Sight. — The receptive nervous organ of vision is the retina. This has an extremely complicated structure, which may be divided into the following nine layers : 1. The layer of pigmented epithelium, Avhich lies next to the choroid coat of the eye, and is, therefore, the most deeply situated coat of the retina ; 2, the layer of rods and cones ; 3, the external limiting membrane ; 4, the outer granular layer ; 5, the outer molec- ular layer ; 6, the inner granular layer ; 7, the inner molecular layer ; 8, the ganglionic layer • 9, the layer of nerve-fibres. Internal to the ninth layer is the internal limiting membrane, which separates the retinal structures from the vitreous humor occupying the cavity of the eyeball. The general character and associations of these layers are shown in Fig. 243. 1. The layer of pigmented epithelium is made up of hexagonal cells, which are separated from each other by a homogeneous cement and form a single continuous layer upon the external sur- face of the retina. They are in contact with the rods and cones of the next layer, and send filamentous prolongations between those structures. The pigment lies within these filamentous processes and the portion of cytoplasm continuous with them, but its position THE ORGANS OF THE SPECIAL SEXSES. 261 varies with the functional activities of the organ. When the eye has been exposed to light the pigment is found lying deeply between the rods. When the eye has been at rest for some time the pigment is retracted in greater or less degree within the body of the cell. 2. The rods and cones are the terminal structures of cells which extend from the fifth layer to the first. The nuclei of these cells Fig. 243. Diagram of the retina. (Kallius.) I., pigmented epithelial layer; II., layer of the rods and cones; III., external limiting membrane ; IV., outer granular layer ; V., outer molecular layer; VI., inner granular layer; VII., inner molecular layer; VIII., ganglionic layer; IX., layer of nerve-fibres, z, pigmented epithelial cells; c, at the bottom of the external limiting membrane, rods ; 6, cone cells ; c-li, ganglion-cells of the sixth layer connecting the fourth layer with the eighth; /.horizontal cell sending a process into the seventh layer; k-q, "spongioblasts," or neurons of the third type (Fig. 217) ; r-w, ganglion-cells of the eighth layer ; x, sustentacular cell of Jliiller, with striated upper end forming a part of the external limiting membrane ; y, ?/, neuroglia-cells. It should he borne in mind that in sections of the retina numerous elements of the various sorts here rep- resented are crowded together to form a compact tissue. The centrifugal fibres which reach the retina from the cerebrum are omitted from this diagram. They arc distributed in the inner granular or sixth layer. The light entering the eye passes through tbe layers represented in the lower part of this figure before it can affect the rods and cones. lie within the fourth layer, to which they give a granular appear- ance (Fig. 243). 3. The external limiting membrane is formed by the cuticulanzed outer ends of certain sustentacular epithelial cells, the "cells of 262 NORMAL HISTOLOGY. Miiller " (Fig. 243, x), which extend from this layer to the in- ternal limiting membrane and serve to support the various elements of the retina. The nuclei of these cells lie in the seventh layer, to the granular character of which they contribute. The portion of the cell which lies in the fourth layer of the retina is indented with numerous oval depressions receiving the nuclei of the cells carrying the rods and cones, which they both support and isolate from each other. The filamentous cell-bodies of those elements are also separated by the cells of Miiller. In the sixth and seventh layers delicate processes from these cells serve a similar purpose, and in the eighth layer their deep extremities fork to give support to the ganglion-cells. Beyond the ninth layer the ends of these forks expand and come in contact with each other at their edges to form the " internal limiting membrane." 4. The fourth, or outer granular layer contains, as already stated, the nuclei and elongated bodies of the cells that carry the rods and cones of the second layer. The bodies of the former are almost filamentous in character, but expand to enclose the oval nucleus, which lies at various depths in different cells. The cell-body expands again near the external limiting membrane, through which it passes to form the rod. At the other end the filamentous cell- body terminates in a minute knob in the fifth layer of the retina. The cells which form the cones have nuclei lying near the external limiting membrane and cylindrical bodies terminating in a brush of filaments in the fifth layer. 5. The outer molecular layer, also called the " outer plexiform layer," owes its appearance to a multitude of filaments, part of which have been described as the terminations of the cells bearing the rods and cones, the rest being the terminations of nerve-processes spring- ing from the cells of the sixth layer. 6. The sixth layer has a granular appearance, because of the presence within it of the cells of a great number of short neurons. These are of two sorts : first, those belonging to the first type, rep- resented in Fig. 217, which have dendrites in relation in' the fifth layer with the filaments of the cells bearing the rods and cones, and neurites that come into relation in the seventh layer with the den- drites of ganglion-cells lying in the eighth layer ; second, neurons of the third type, shown in Fig. 217, which, in this situation have been called "spongioblasts." These, which we may regard as association-neurons, form two groups : first, those which send THE ORGANS OF THE SPECIAL SENSES. 263 processes into the fifth layer ; and, second, those which send their processes into the seventh layer ; but, aside from the neurons in- cluded in these two groups, there are certain cells (Fig. 243, i) which send processes into both the fifth and the seventh layers. 7. The seventh, inner molecular or " inner plexiform" layer owes its delicate structure to the fact that it is here that the teleneurites of the cells in the sixth layer come into relations with the teledendrites of the ganglion-cells of the eighth layer. 8. The eighth layer contains those ganglion-cells whose teleden- drites receive impressions from the teleneurites derived from the sixth layer, and send their neurites into the optic nerve. These neurites form the chief constituent of the ninth layer of the retina. It will be observed in Fig. 243 that the basal expansions of the cells bearing the cones are mostly in relation with the teledendrites of a single neuron of the sixth layer, and that this neuron is, again, in close relations with the teledendrites of but one ganglion-cell of the eighth layer. This arrangement would not favor a diffusion of Fig. 244. Diagram of the nervous mechanism of vision. (R. y Cajal.) A, retina; B, optic nerve; C, corpus geniculatum. a, cone ; b, rod ; c, d, bipolar nerve-cells of the outer granular layer ; e, ganglion-cell ; /, centrifugal teleneurites ; g, " spongioblast" ; h, teleneurites from optic nerve: ;', neuron receiving and further transmitting the nervous impulse ; r, cell trans- mitting the centrifugal impression. The courses of nervous impressions are indicated by the arrows. the impressions inaugurated in the cones. The arrangement is quite different in the case of the cells bearing the rods. The probable course of nervous impressions to and from the retinal elements is represented in Fig. 244. PART II. HISTOLOGY OF THE MORBID PROCESSES. CHAPTER XX. DEGENERATIONS AND INFILTRATIONS. As the result of disturbances in the internal economy of the cell, a variety of changes, called degenerations or infiltrations, are occa- sioned, some of which are accompanied by visible alterations in the structure of the cell or of the intercellular substances. "We are so ignorant of the exact nature of the normal processes carried on by the cell that it is impossible for us to furnish an explanation of most of these changes clue to abnormal conditions. We can only describe and group the results according to their apparent likenesses until such time as an increased knowledge permits a more enlightened conception of their significance. The degenerations are changes in which one of the results is the conversion of a part of the normal structure into some other sub- stance. They imply a loss on the part of the tissue-elements suffer- ing the change. The infiltrations are departures from the normal in that material from without is deposited either within or between the tissue-ele- ments in an abnormal form or degree. They imply a gain of material, but not necessarily an advantageous gain, on the part of the tissues affected. Such general statements of an obscure subject must inevitably be vague. They are largely based upon theoretical considerations, and it becomes difficult in many cases to decide definitely whether a given condition is due to degenerative changes or is the result of infiltration, or whether both processes may not have contributed toward producing the abnormal appearances which are observed. 266 HISTOLOGY OF THE MORBID PROCESSES. It must be borne in mind that changes which are morbid in a given part of the body may be included in perfectly normal proc- esses carried on in other parts, and are, therefore, not beyond the pale of possible normal cellular activity. In fact, most of the morbid processes observed find parallels in the physiological activ- ities of some portion of the body. In bone, for example, it is a pathological condition when the intercellular substance fails to be impregnated with earthly salts ; but if such salts are deposited in the somewhat similar fibrous inter- cellular substance of the closely related tissue forming a ligament, the process is then morbid. The two tissues are closely related in structure and are built up by cells having a common, not very remote, ancestry : yet the uses the cells made of the materials brought to them are, to us, very different, and, as yet, inexplicable. Nor do we know much concerning the way in which, or the extent to which, normal conditions must be modified in order to occasion visible morbid changes in the tissues. We do know that apparently very slight alterations in those conditions may cause pro- found tissue-changes, as is exemplified in the cachexia following extirpation of the thyroid gland (see p. 183). The amount of thyroid secretion allotted to individual cells of the body must be almost infinitesimal, but its importance is strikingly demonstrated when the cells are deprived of that supply. In this case we have at least an inkling of how slight an abnormal condition may suffice to work profound alterations in the cellular economy. When, therefore, we meet with evidences of a marked disturbance of the processes within the cells of a tissue, or of their formative activities, we need feel no surprise if an explanation of the causes underlying those morbid manifestations is incomplete or even entirely wanting. 1. Albuminoid and Fatty Degenerations. — These two forms of degeneration are frequently associated with each other, and have so much in common that they may well be considered together. They both affect the cells of the parenchymatous organs, such as the kidney, liver, and other secreting glands, the heart and other muscles. Albuminoid, or " parenchymatous," degeneration results in a swelling of the cells, with an increased granulation of their cytoplasm. The granules are rendered invisible when acted upon by weak acids or alkalies, and are considered to be of albuminoid nature. They DEGENERATIONS AND INFILTRATIONS. 267 are formed at the expense of the cytoplasm, or, at any rate, the cytoplasm disappears as they accumulate. If the change be only moderate in degree, it is possible for the cell to return to its normal condition. The granules then disap- pear, the cell recovers its original size, and there is no trace of the morbid condition left. But the degeneration may be too extensive to p?rmit of recovery. The cell then suffers disintegration ; the granules become more abundant, the normal cytoplasm disappears, Fig. 245. *■■*- Parenchymatous nephritis, a, cross-section of a convoluted tubule of the kidney, the lin- ing epithelium of which is the seat of albuminoid degeneration. The cells are swollen and their bodies filled with abnormally coarse granules. The cells to the left are so far disintegrated that the nuclei have lost most of their chromatin. Such cells cannot recover. The cells to the right are less profoundly altered and their nuclei retain suf- ficient chromatin to stain slightly. These cells might, perhaps, recover. Other con- voluted tubules, similarly affected, are represented in oblique section. 6, tubule with low, unaffected epithelium, the nuclei of which stain deeply ; e, round-cell infiltration of the interstitial tissue in the neighborhood of a Malpighian body, the edge of which is just above the line c. Section stained with hcematoxylin and eosin. and the nucleus falls into fragments (" karyolysis "), the whole cell being reduced to a granular debris exhibiting no evidence of organ- ization (Fig. 245). 2GS BJSTOLOHY OF THE MORBID I'UOCESSES. In fatty degeneration the process is similar to that already described as taking place in albuminoid degeneration; but here the albuminoid granules are replaced by globules of fat. These vary in size from mere granules of minute dimensions to distinct globules of considerable diameter (Fig. 246). The fat is left Fig. 246. $ Fatty degeneration of the cardiac muscle (Israel.) In some portions of the preparation the eroKS-striations of the contractile substance are retained. In these portions the fatty metamorphosis has not taken place. In other places the contractile substance has been destroyed and the cells are charged with minute granules and with small globules of fat. The preparation is unstained, so that the nuclei are not prominent. They have been omitted from the figure. Specimen prepared by teasing the fresh tissue. unchanged upon treatment with weak aeids or alkalies, and is stained a dark brown or black by solutions of osmic acid (see Fig. 1S(J), reactions which distinguish fatty from albuminoid granules. They are, furthermore, dissolved by ether or strong alcohol, which leave albuminoid granules undissolved. In specimens which have been hardened in alcohol the fat is removed from the cells, which then contain little clear spaces in which the fat was situated in the fresh condition of the tissues. This removal of the fat is likely to be still more perfect if the specimen lias been embedded in cel- loidin, solutions of which contain ether. Albuminoid degeneration occurs in acute diseases, such as the exanthemata, typhoid fever, septicaemia, etc., which are all char- acterized by fever. It also occurs in cases of damage to the tissues, insufficient immediately to kill the cells, but great enough to induce inflammation. Because of this frequent association with inflam- matory changes in other tissue-elements albuminoid degeneration has been termed "acute parenchymatous* inflammation." The dam- age may be the result of some externally applied injury, or it may be occasioned by a sudden diminution, but not complete arrest, of the nutrient supply; c. MU<:XHn.tTIOXS AXI> [NVILTUATIONS. 279 nephritis appears to bo colloid elaborated by the cells lining the renal tubules, but (hose casts may not always owe their origin to this form ol' defeneration. Fin. i*.l. .i^ V-.;^^Vy € ? C "'■■;■■ rY - * > -s. • "" ■ < > S Fi.i. nr.i ,, J >. ^"')^S i / »"- i 'i^Jrf „- I '//» ••'.-:' *-<(■ V>v Lobule of the liver, showing atrophy from chronic passive congestion. (Ttibbert.) In the centre is the central vein, with slightly thickened walls. Surrounding this are the di- lated capillaries, forming the intralobular vessels, between which are the atrophic liver- cells containing pigment. This pigment is probably of biliary origin. The pressure upon the cells must interfere with the discharge of the bile through the bile-capillaries (Figs. 127 and 128), and lead to an accumulation of its constituents within the cells, ^\ here the pigment collects. passed through the other parts of the vascular system within the liver. The capillaries are enlarged around the central vein; the hepatic cells between them are diminished in size and pigmented (Fig. 258). The growth of tumors may exert a pressure upon neighboring parts, causing their atrophy, the explanation of which is similar to that of atrophy of the liver as the result of passive hyperemia. Pressure upon a tissue does not always, however, occasion atrophy. If the function of a part be to resist pressure, an increase of press- ure may lead to hypertrophy, provided the nutrient supply be sufficient. Thus pressure upon the walls of a bloodvessel may cause them to increase in thickness. Aside from the two forms already mentioned, atrophy mnv be the result of a diminution in the nutritive supply: local, as the result of disease in the vessels of a part; general, when all the vessels are ATROPHY. 287 affected with disease, or when the general nutrition of the body is reduced. Both these causes operate in the general condition known as " senile atrophy." More obscure forms of atrophy are those which appear to be occasioned by lesions of trophic nerves, or are caused by toxic con- ditions ; e. g., lead-poisoiiiug. CHAPTER XXII. HYPERTROPHY AND HYPERPLASIA. By hypertrophy is meant an increase in the size of the elements composing a tissue ; by hyperplasia, an increase in their number. Both conditions usually lead to an enlargement of the organ in which they are found, but this is not necessarily the case, for all the elements in the organ need not participate in the increase; some may diminish in bulk. 1. Functional Hypertrophy. — This process, like that of functional atrophy, depends upon the activity of the part undergoing the change. In this case the parenchyma of the part is increased to meet a gradually increasing demand for the work it is fitted to perform. This increase may take the form of hypertrophy or that of hyperplasia. The muscular tissues meet the demand bv an increase in the size of the muscle-cells. This is illustrated in the hypertrophy of the heart in valvular lesions, which throw extra work upon the muscle ; in the enlargement of the uterus during gestation, fitting it for the strong contractions during labor ; and in the enlargement of the voluntary muscles by exercise. In glandular organs an additional demand for work results in hyperplasia, in which the epithelial cells of the parenchyma multi- ply (Fig. 259). Functional hypertrophy, or hyperplasia, takes place only under certain favorable conditions. The demand for extra functional activity must not be too great, otherwise degenerative changes ensue. The same result would follow were the nutritive supply insufficient to meet the loss of material and force sustained by the cells in doing the increased work. It is evident, then, that the condition occasioning the hypertrophy or hyperplasia must develop gradually, and not interfere with the supply of nutrition. The nature of the tissue also influences the result. In general, it may be stated that tissues of high specialization are less capable of cither hypertrophy or hyperplasia than those less specialized, and that hypertrophy is the rule in tissues of higher function, while HYPERTROPHY AND HYPERPLASIA. 289 hyperplasia is more common in those of lower function, where the formative powers of the cells are less in abeyance. Compensatory hypertrophy is a term applied to functional hypertrophy or hyperplasia following the destruction of an organ or part of an organ. This leads to an increase of the work demanded of other parts capable of performing the function normally carried on by the part destroyed, or capable of assisting the function that has Fig. 259. US) i®i © -., v-;:i w ,v^#A Necrosis of part of an hepatic lobule, (v. Meister.) a, necrosed cells, the nuclei of which have lost their affinity for dyes ; &, hypertrophic cells with large nuclei ; c, detritus of blood-corpuscles in the capillaries. Section taken eighteen hours after removal of a por- tion of the liver in a rabbit. The section is taken at the margin between that tissue which is affected with necrosis and that which retains life, but is stimulated to prolifera- tion by the irritative effects of the amputation. After a while the hypertrophied epithe- lial cells will divide by karyokinesis and attempt a restitution of the lost tissue — a species of compensatory hyperplasia. suffered diminution. Thus, disease of one kidney may indirectly occasion hypertrophy of the other kidney, or, more properly, hyper- plasia of its functional epithelium, or chronic interstitial nephritis affecting both kidneys may lead to hypertrophy of the heart by throwing more labor upon that organ in order that the remaining renal parenchyma may perform the work demanded of the kidneys. In like manner the auxiliary muscles of respiration may become hypertrophic in eases of embarrassed respiration. 1 Functional hypertrophy may also find expression among the con- 1 Attention has already been called to the hypertrophies of the hypophysis and parathyroids in cases of thyroidectomy or disease of the thyroid gland (see p. 191). 19 290 HISTOLOGY OF THE MORBID PROCESSES. nective tissues of the body, in which the usefulness of the tissue resides in its physical properties. In muscular individuals the bony ridges giving attachment to the tendons are more strongly accen- tuated than in those whose muscles are less highly developed. A very familiar illustration of functional hyperplasia is furnished by the skin of the palms. Manual labor that is habitual occasions a thickening of the epidermis due to hyperplasia ; exceptional over- work causes damage leading to inflammation, blisters. 2. Developmental Hypertrophy. — Hypertrophy of a part occasion- ally arises without assignable cause and apparently as a mere anomaly in development. Such structures as horns and warts are examples of this form of hypertrophy, which are not readily separated from the group of growths called tumors. When the growth is limited and not progressive it may in most cases be attributed to this form of hypertrophy; when apparently unlimited, progressive, and atyp- ical in structure, it must be classed among the tumors. 3. Inflammatory Hypertrophy. — Under the influence of damaging agents which act with such mitigated intensity that their effect upon the cells amounts merely to a decided irritation, the formative powers of the cells may be stimulated and an enlargement of the part be brought about, either as the result of hypertrophy or of hyperplasia of its elements. This form of hypertrophy is nearly, if not quite, equivalent to the results of chronic productive inflam- mations, for an account of which the student is referred to another chapter. In cases where the evidences of damage are inappreciable the process may be considered as irritative hypertrophy or hyper- plasia ; where they are at all marked, it must be regarded as inflam- matory. The microscopical evidence of hypertrophy is found in an increase of size in the elements composing the tissue. It is not a simple matter to decide from a microscopical examination whether hyper- plasia exists or not, for the microscopical appearances are almost, if not quite, normal. It is often necessary to consider the changes in the gross appearances of the part in order to determine whether its constituent elements have increased in number or not. CHAPTER XXIII. METAPLASIA. When a fully developed tissue becomes modified in its structure to resemble another form of adult tissue, without passing through an intermediate stage of indifferent or more embryonic tissue, the process is known as " metaplasia." It differs from the inflammatory process in that the rejuvenescence of the tissue is not obvious, and it is unlike the development of a tumor because the tissue-change is a conversion of one form of tissue into another, and not the pro- duction of a new tissue within another. Metaplasia only results in the formation of a tissue closely allied to that in which it, takes place. It is most commonly met with in the connective tissues, where a change in the character of the inter- cellular substances and in the form of the cells, which all spring from the same original source, the mesoderm, is all that is necessary to convert one form of connective tissue into another variety of the same group. We must attribute the change to a modification in the functional activity of the cells, the reasons for which are in most cases very obscure. We may, perhaps, in some cases, seek the explanation in conditions that lead to an altered functional demand on the part. Thus, for example, it has been noticed that bone sometimes develops in the fibrous tissues of the thigh or shoulder in soldiers that are obliged to ride or carry a musket for a long time. It may be that the fibrous tissue becomes reinforced in these cases with bone, because it is better calculated to withstand the pressure ; but the fact that such cases are exceptional shows that this response on the part of the tissues is by no means con- stant and that the explanation is incomplete. Metaplasia may result in the conversion of fibrous tissue into mucous or osseous tissue ; hyaline cartilage into fibro-cartilage, or into fibrous, mucous, or osseous tissue ; adipose tissue into mucous tissue, etc. The metaplastic tissue is usually not typical ; that is, it differs somewhat from the normally developed tissue in the finer details of its structure. Thus, the bone that is produced by meta- 291 292 HISTOLOGY OF THE MORBID PROCESSES. plasia from fibrous tissue lacks the elaborate system of canaliculi that is found in normally developed osseous tissue, although in its essential features it is virtually bone, the intercellular substances being impregnated with calcareous matter and yielding gelatin on boiling. Epithelial tissues may also be the seat of metaplasia. Under the influence of moderate but repeated damage, columnar epithelium may become modified into a stratified variety. In such cases the cause may, presumably, be traced to a change of conditions, which calls for an unusual exercise of the protective function of the epi- thelium. The uterine cavity and the respiratory tract are the most common situations in which this transformation of epithelium is met with. A similar conversion of transitional epithelium into true stratified epithelium is occasionally met with in the bladder and renal pelvis, as the result of a calculus not causing sufficient damage to induce an active inflammation. Metaplasia appears to result from a change in the functional activities of the cells, which lose their accustomed form of special- ization and acquire new ones of closely related character. CHAPTER XXIV. STRUCTURAL CHANGES DUE TO AND FOLLOWING DAMAGE. I. NECROSIS. The term necrosis designates a local death of tissue during the life of the individual. In our study of the normal tissues under the microscope we are obliged to use methods of preparation which, in nearly all cases, kill the tissues before they come under observation. When we examine them with a view to determining their structure, they are nearly always necrotic, if we may use that term in this connection. Our standards of the normal appearances are, therefore, largely based upon what we learn from recently killed tissues. In some instances it is possible, however, to examine even highly developed tissues while still living. If, for example, the super- ficial layer of a frog's cornea be stripped off and mounted in a drop of serum, the cells composing it may be readily seen under the microscope. While such a preparation is quite recent it is difficult to distinguish clearly the nuclei within the cells, their refractive indices being nearly the same as that of the surrounding cyto- plasm ; but in a short time the nuclei suddenly become very distinct, as though they had undergone a sort of crystallization. This is probably an indication of the death of the nuclei, the substances composing them having suffered a coagulation which increases their powers of refracting light and, in consequence, the distinctness with which they are seen. This conclusion is strengthened by the fact that the change may be hastened by the application of reagents, such as acetic acid. The modern methods of preparation used in histological studies aim at bringing about a sudden death of the cells and such a coag- ulation of the tissue-elements as shall prevent further changes of structure before the tissues can be studied. For, if the tissues are allowed to die spontaneously, their elements suffer changes that greatly alter their appearance. When they die and remain within 293 294 HISTOLOGY OF THE MORBID PROCESSES. the living body, as is the case in necrosis, those changes in structure are more diverse and more marked than those incident to spontaneous death resulting from removal. This has led to the distinction of several varieties of necrosis, characterized by different structural changes in the dead tissue, which are dependent upon the conditions obtaining in the tissue at the time of death or after death has taken place. Among the most striking changes incident to necrosis are those affecting the nucleus. This may retain its form in great measure, but lose its affinity for the nuclear dyes (" chromolysis," Fig. 262), or the chromoplasmic substances may retain that affinity, but be broken up into fragments, thus destroying the form of the nucleus ("karyolysis," Figs. 260 and 261). Both of these changes are indicative of the death of the nucleus and assure the death of all parts of the cell. Fig. 260. Fig. 261. Fig. 262. ♦ v - ... « , « * Changes in the nnclei of renal epithelial cells incident to necrosis. (Scnmaus.) Fig. 260.— Destruction of the chromatic reticulum and condensation of the chromatin in masses of various sizes ; early stage of karyolysis. Nuclear membrane nearly gone. Fig. 261.— More advanced stage of nuclear destruction. The nuclear fragments lie free in the cytoplasm ; later stage of karyolysis. Fig. 262.— Disintegration and disappearance of the chromatin without a coincident disinte- gration of the form of the nucleus-chromolysis. 1. Coagulation-necrosis. — When the tissues that have suffered death liberate fibrinoplastic substances and fibrin-ferment these interact with the fibrinogen in the lymph and occasion a coagula- tion of the necrosed tissue analogous to the production of fibrin. These coagulated materials may appear as fine granules or as hyaline masses of a dense, glassy character. This form of necrosis is illustrated in the formation of the " membrane " in diphtheria, which is the superficial portion of the affected part that has under- STRUCTURAL CHANGES DUE TO DAMAGE. 295 gone coagulation-necrosis (Fig. 263). When the granular form of coagulation-necrosis is associated with albuminoid and fatty degen- eration the result is a cheese-like mass, and the process is known as cheesy degeneration (p. 274). 2. Colliquative Necrosis (Fig. 281). — This form of necrosis is fol- lowed by an imbibition of fluid, occasioning a disintegration of the Fig. 263. e / e Edge of a diphtheritic membrane. Section from the human uvula. (Ziegler.) u, normal stratified epithelium ; b, subepithelial fibrous tissue of the mucous membrane ; c, epithe- lium that has undergone coagulation-necrosis. Only remnants of cells remain in the coarse fibrinous meshwork. d, oedematous subepithelial fibrous tissue containing fibrin and leucocytes ; e, bloodvessels; /, hemorrhage ; g, g, groups of the bacteria causing the necrosis. tissue-elements, which are broken up into a granular detritus sus- pended in the fluid. The foregoing two forms of necrosis may be associated with each other, or one may follow the other. The fate of the necrosed tissue depends upon a variety of circum- stances. The presence of dead tissue excites an inflammation in the living tissue surrounding it, and the character of this inflam- mation often determines the fate of the necrosed mass. (See article on inflammation.) The situation of the dead tissue also affects the result. The following examples will serve to illustrate these vari- ations : 1. Absorption. — The necrosed tissue-elements become disin- tegrated, and the debris either dissolved or carried away through the lymphatic channels by the currents of fluid, or through the 296 HISTOLOGY OF THE MORBID PROCESSES. agency of leucocytes, which incorporate them and then pass out of the necrotic area. This disintegration appears to be due partly to a simple maceration or separation of the particles of the tissue, partly to a solvent action exerted by the fluids in the tissues upon dead organic matter. While absorption is going on there is an inflammatory reaction in the surrounding tissues that still retain life, which results in the formation of cicatricial tissue. This may ultimately occupy the site of the necrosed tissue, or it may form a capsule around a collection of fluid occupying that site, the result being a cyst with a fibrous wall. 2. Encapsulation. — The necrosed tissues may remain unab- sorbed, or be only partly absorbed, and eventually become enclosed in a capsule of new-formed fibrous tissue arising through the inflammatory process mentioned above. In this case the necrosed mass becomes desiccated through absorption of its fluid constituents, and may eventually be infiltrated with lime-salts, calcified. 3. Gangrene. — This occurs in two forms, distinguished as dry and moist gangrene. Dry gangrene is due to the desiccation of dead tissues that are exposed to the air. The tissues become discolored, owing to changes in the coloring-matter of the blood, and shrink, the skin assuming the appearance of parchment. After a time the dead mass is cast off by the formation of granulatiou-tissue from the neighboring living tissues. Moist gangrene is the result of putrefactive changes in dead tissue, due to infection with bacteria causing decomposition. The parts are discolored, swollen, moist, and often contain bubbles of gas having a foul odor. The gangrenous part may here also be cast off as the result of the formation of granulations, but the gangrenous process may spread before it can be checked by an inflammatory demarcation, the products of decomposition having a poisonous effect upon the neighboring tissues that leads to necrosis and prevents the development of granulation-tissue. 4. Suppuration. — If the dead matter contain pyogenic micro- organisms, they exert a peptonizing action upon the necrotic mass, causing it to liquefy. At the same time they excite a purulent inflammation in the surrounding tissues which leads to the forma- tion of an abscess or an ulcer. In those cases of necrosis in which the necrosed tissues are not speedily absorbed the dead mass is known as a " sequestrum," and STRUCTURAL CHANGES DUE TO DAMAGE. 297 the zone of inflammation separating it from the living tissues is called the line or plane of demarcation. (For a fuller explanation of the process of demarcation and of the tissue-changes that lead to encapsulation, the student is referred to the article on inflamma- tion.) II. INFLAMMATION. It is difficult to frame an accurate definition of inflammation, for the reason that the term includes a number of different conceptions that cannot be readily expressed in concise form. In general, it may be stated that inflammation is a process of repair following a limited damage to the tissues. The injurious agent acting upon a part must inflict a certain amount of damage in order to bring about inflammation : if its action be slight, it will cause only an evanescent irritation which does not pass into inflammation ; if, on the other hand, its action be severe, it occasions necrosis or degenerative changes at the point of its application, and only in remoter parts of the tissue, where its action is moderate, will inflammatory changes be manifested. The nature of the damaging cause and that of the tissues affected both influence the character of the inflammatory process. It therefore manifests many variations under different circumstances, and in order to understand the underlying principles of the process it will be best to select some particular example for a somewhat close study, and then to consider some of the circumstances that modify the phenomena presented by that example. A severe burn, the effects of which extend deeply enough to destroy a part of the true skin, will serve this purpose, as affording an example of acute inflammation of a vascularized part following a cause that has acted for only a short time and has then been removed. In considering this example we must distinguish between those destructive effects that are due to the damaging cause, and the reparative processes that follow in the tissue-elements that have been less seriously affected. It will make the example clearer if we also separately consider the phenomena presented by the vascular system from those taking place in the fixed tissues of the part exclusive of the bloodvessels. Those tissues which have come into the closest contact with the source of heat will have been quickly killed and, perhaps, charred. Beyond this point of complete destruction the tissues may be roughly 298 HISTOLOGY OF THE MORBID PROCESSES. divided into zones, in which the direct damage is successively less marked. In the first zone necrosis will have taken place ; in the tissues that are more remote, degenerative changes will be occa- sioned ; and still farther away from the seat of injury the tissues will show a vital reaction to the stimulation or irritation they have received, which will reveal itself in a growth, eventually leading to a repair or patching of the defect in the tissues occasioned by the damage. 1. The Bloodvessels and tie Circulation. — The vessels most seri- ously damaged, together with the blood they contained, will have been completely destroyed ; in those less affected the circulation will have been arrested and the blood coagulated. But beyond the zones in which the function of the circulation has been abolished the first marked effect is an increase in the volume and rapidity of the current of blood. This increased flow of blood to the part is attributed to the action of the injury upon the vaso-motor system of nerves, causing a relaxation of the walls of the arteries supply- ing the part which has been damaged. A similar increase in circu- lation follows slighter stimulation of the skin, as, c. g., rubbing, so that this determination of blood to the part as the result of vaso- motor disturbance is comparable with entirely normal hyperemias ; but it is greater in degree when the irritation of the parts is great enough to cause damage. After an interval the velocity of the circulation in the part which is becoming inflamed is reduced, without any diminution in the calibre of the vessels, and the slackening of the current may pass into complete stasis. This is probably due to two causes : first, to the extension of the vaso-motor disturbance beyond the area of the injured part, so that collateral branches of the main arteries are dilated ; this would diminish the pressure of blood going to the inflamed part. Second, to alterations in the walls of the smaller vessels in the inflamed part, especially the capillaries and small veins. These become more pervious, probablv as the result of the damage they have sustained in common with the other tissues, allowing a greater amount of fluid to pass through them than when they were in the normal condition. This comparatively rapid extraction of its watery constituent increases the viscosity of the blood, and that increased viscosity, together with the changes in the walls of the vessels, increases the friction between the two, impeding the cir- culation. STRUCTURAL CHANGES DUE TO DAMAGE. 299 Thus, two influences appear to check the flow of the blood after the inflammatory process has been inaugurated : (1) a diminution of the pressure urging the blood forward, and (2) an increase in the resistance offered to the passage of the blood through the smaller vessels. To these, another factor increasing the resistance is added as soon as the current has become slowed beyond a certain point. During the normally rapid flow of the blood the corpuscles it con- tains, being heavier than the serum, form a column in the axis of the vessels, with a clear zone of serum around it (Fig. 264). This is in accordance with the physical laws governing the behavior of sus- pended particles in fluids circulating in a tube ; but if the rate of flow be diminished beyond a certain point, the suspended particles Fig. 264. w Q^Sti^^f the section during its preparation, c, leu- cocytes beneath the endothelium of the vascular wall ; d, oedematons fibrous tissue sur- rounding the vessel. The fibres of the tissue have been separated by the exuded serum. This tissue is also moderately infiltrated with leucocytes that may have passed through the walls of the vein, and contains a few red blood-corpuscles, c, wall separating two pul- monary alveoli. This is also somewhat infiltrated with leucocytes. /, exudate within an alveolus, consisting of serum, fibrin, leucocytes, and red blood-corpuscles; it also con- tains a few epithelial cells desquamated from the alveolar wall, g. inflammation, may have a more complex causation. It may be due to the immediate effects of the injury that occasioned the inflam- mation, to disturbance of nutrition, to the presence of the exudate, or perhaps to an interruption of the normal nervous mechanism. All these disturbing factors are present, and may vary in their potency in different eases. All the changes that have been hitherto described are the imme- diate or only slightly remote effects of the damage to the tissues, and have nothing to do with the process of repair. They may be STRUCTURAL CHANGES DUE TO DAMAGE. 303 regarded as constituting the destructive phase of acute inflamma- tion. 2. The Fixed Elements of the Tissues. — It is evident that the cause of damage itself, or the disturbances of nutrition resulting from the changes in the circulation, must either cause rapid death, necrosis, or that slower form of death entailed by a relatively in- sufficient supply of nourishment, which has been described in the chapter on the degenerations. The cells are either killed at once, or are starved within a certain radius of the point at which the cause of the inflammation was applied. Beyond this radius these changes give place to those that bring about repair. But the susceptibility of the different tissue-elements varies : an injury that would kill some might hardly affect others; a given degree of innutrition might cause degeneration in some and not in others, «o that the depth to which those changes are felt will depend upon the nature of the tissues present. In general, it may be stated that those tis- sues which are highly specialized and those which carry on functions requiring active intracellular metabolism are the ones most deeply affected by damaging influences. Repair. — The view was at one time strongly upheld that emi- grated leucocytes were active in the formation of the new tissues that developed during inflammation. These corpuscles were re- garded as of indifferent character, capable of differentiation into the various forms of connective tissue. This view has not been supported by the results of experimental study, and is now aban- doned, giving place to a revival of the earlier belief that the cells of the fixed tissues are the active elements in the reparative process which results in the formation of new tissues. Since the significance of the mitotic figures during karyokinesis has been learned, it has become possible to ascertain positively that the fixed cells multiply beyond the zone of destruction in acute inflammations. The cells which have suffered neither destruction nor degeneration beyond their powers of recuperation undergo a species of rejuvenescence, returning to a comparatively undiffer- entiated condition, in which their powers of reproduction and tissue- formation are revived. It is as though they reverted, under the influence of strong irritation, to the condition in which their pro- genitors existed at an earlier stage of tissue-development. The process of repair depends upon this capacity for rejuvenescence on the part of the cells of the tissues, but that power varies greatly in 304 HISTOLOGY OF THE MORBID PROCESSES. the cells of different tissues, being, roughly, inversely proportional to the degree of specialization to which they have attained. Those tissues whose functional activities in the adult are chiefly formative possess this capacity for rejuvenescence in a high degree. In fact, epithelium in many situations — c. g., upon the skin — merely requires a little stimulation of its normal activities to produce new tissue. The case is different with tissues of higher function, in which the cells have become greatly specialized at a sacrifice of their formative activities. In these the capacity for rejuvenescence is always com- paratively slight, and may be entirely lost ; as, for example, in the ganglion-cells of the central nervous system. Such parenchymatous cells of high function are also more vulnerable than cells of a lower type of specialization, because they are more dependent for their functional activity upon a maintenance of the normal conditions of nutrition. The foregoing considerations explain why the more highly spec- ialized cells are damaged for a greater distance from the point of injury than are the connective-tissue cells, and also why the) 7 play a less prominent part in the restorative processes that follow those which have been destructive. The result is that the zone of con- nective tissue capable of rejuvenescence is nearer to the site of injury than the zone which includes undegenerated cells of higher function, and from this it follows that the defects in the tissues are made good by a proliferation of connective tissue, accompanied in only slight degree by a proliferation or restitution of the tissues of greater specialization. The process of repair is more a patching of the defect than a restoration of the normal structure. It results in a permanent scar, and not the perfect replacement of lost tissues by others of the same structure and function. During rejuvenescence the cells of the connective tissues enlarge and become more cytoplasmic, and their nuclei become richer in chromatin. They then divide by the indirect process, giving rise to a number of spheroidal cells, which, together with newly devel- oped loops of capillary bloodvessels, constitute an undifferentiated tissue, called "granulation-tissue." During its formation at least a part of the original fibrous intercellular substance appears to be re- moved by absorption. This may be brought about by maceration in the fluids present, or through the agency of the leucocytes that have emigrated from the vessels and play the part of phagoevtes (Fig. 269). The young vascular loops that supply the granulation-tissue are STRUCTURAL CHANGES DUE TO DAMAGE. 305 Fig. 269. Section from adipose tissue in the neighborhood of a phlegmonous inflammation due to infection with streptococci. (Grawitz.) F, the boundaries of fat-cells, the tissue repre- sented being the connective tissue between those cells. Four large karyokinetic figures arc seen in that tissue : these are in the rejuvenescent cells of the fibrous tissue. The section also contains leucocytes that have wandered into the tissue from the neighbor- ing focus of exudation. These are designated by the letters L and c. ci and c 2 arc con- nective-tissue cells undergoing destruction, their nuclei showing chromolysis. Other connective-tissue cells show a swelling of the nucleus (karyolysis), and the interstitial tissue is the seat of a moderate cedema. produced through a similar rejuvenescence of the endothelial cells of the older capillaries. Those cells become richer in cytoplasm, and acquire a strong resemblance to epithelial cells (Fig. 270). They then multiply, forming little collections of cells in contact at Fig. 270. Sections from granulations forty-eight hours old. (Nikiforoff.) In both A and B two capil- laries are represented, a, young connective-tissue cell ; ai, karyokinetic figures in such cells ; b, b t , 6 2 , leucocytes with single, polymorphic, or fragmented nuclei, the latter suf- fering karyolysis and, consequently, death ; c, endothelial cell with nucleus in spirem. stage of karyokinesis, demonstrating the proliferation of those cells. 20 306 HISTOLOGY OF THE MORBID PROCESSES. one point with the walls of the capillaries and reaching out in col- umns or bands among the cells of the granulation-tissue. Here they may become united with each other, forming loops that spring from the same capillary vessel, or connect it witli other capillaries. Sub- sequently these solid columns or bands of cells become channelled, the cells forming the walls of the new vessels, the lumina of which communicate with those of the parent capillaries (Fig. 271). Fig. 271. New-formation of bloodvessels in granulation-tissue. (Birch-Hirschfeld.) The granulation-tissue thus formed is continuous with the adja- cent uninjured fibrous tissues, and serves to separate the tissues that have been killed or have undergone irrevocable degeneration from the living tissues that lie beneath it. The dead mass is finally loosened and cast off, leaving a surface of growing granulations. While the cells in the superficial portions of this granulation-tissue continue to multiply and produce fresh, young, undifferentiated tis- sue, the deeper portions undergo differentiation, the formative powers of the cells being no longer preoccupied with the production of new cells, but diverted to the elaboration of intercellular substances of a fibrous character (Fig. 272). During this process the cells dwindle in size as the intercellular substances accumulate between them, and may suffer complete extinc- tion. This may be due to atrophy in consequence of pressure exerted by the fibrous constituent of the intercellular substances, which has a marked tendency to shrink as it becomes older. Another probable reason for the disappearance of many of the cells may be the lack of a well-defined lymphatic circulation in the granulation-tissue and the young cicatrix, which, if it existed, would serve to assist STRUCTURAL CHANGES DUE TO DAMAGE. 307 ill the nutrition of the tissue. There is a manifest advantage to the whole organism in this absence of lymphatics in granulation- tissue, for the absorption of injurious substances from the region beyond the granulations is hindered. But the nutrition of the granulations themselves is impoverished and the fibrous tissue Fig. 272. Newly formed fibrous tissue from a case of pleurisy : a, pulmonary alveolus filled with an exudate largely composed of leucocytes (pneumonia ; stage of gray hepatization passing into resolution) ; 6, alveolus, from which the disintegrated exudate has fallen out. Before the alterations in structure due to inflammation took place this alveolus, and the one above it, lay immediately beneath the pleura. The thin pleuritic membrane has now been destroyed and its place taken by the fibrous tissue of inflammatory pro- duction, which fills nearly the whole field of vision, c, thin-walled bloodvessel in that fibrous tissue. This and those like it form a part of the older portion of the granulation- tissue which has replaced the fibrinous exudate at first covering the lung (see p. 313). The granulation-tissue between these vessels has organized into a young fibrous tissue, d, younger granulation-tissue ; e, recently formed bloodvessel in the latter ; /, masses of carbon deposited in the tissues by leucocytes, which have transported it thither from the air-passages. These deposits existed before the acute inflammation began. This form of pigmentation is called " anthracosis." that results from its differentiation is of comparatively low vital- ity. While the tissue is young, succulent, and highly vascular- ized by capillaries, this deficienc}' in its organization may not be apparent ; but as the intercellular substances contract they com- press the vessels and cause obliteration of many of them, with atrophy and disappearance of their cellular walls (Fig. 273). 308 HISTOLOGY OF THE MORBID PROCESSES. When, as in the example originally chosen, the injury affects tissues that are normally covered with epithelium, the cells of that tissue proliferate at the edges of the granulations until a layer of epithelium completely covering them is produced. The whole proc- ess of repair comes to an end with the formation of a dense fibrous tissue that is only slightly vascularized by thin-walled bloodvessels and is poor in cells. This is the scar, composed of " cicatricial " tissue (Fig. 273). Upon the skin it is covered with epithelium ; Fig. 273. Dense fibrous tissue, or cicatricial tissue resulting from purktirditis : a, fibrous tissue, almost devoid of nuclei and vessels derived from granulation-tissue ; b, lumen of a small remaining vessel; c, moderate round-cell infiltration in the deeper portion of the fibrous tissue, resulting from an immigration of leucocytes, and, perhaps, also from a slight irritative proliferation of the fixed cells of the tissue ; d, subpericardial adipose tissue. but there are no papillae beneath this covering, and the epithelium is as poorly nourished as the cicatricial tissue beneath it. The cells of higher function in the damaged part which have not been irremediably injured pass through the changes that will pres- ently be described in the section on regeneration. The course of a simple acute inflammation, as outlined above, may be modified and complicated by a number of circumstances to such an extent that these variations must be briefly described. 1. The Healing of Fractures. — When a bone is broken the rejuv- STRUCTURAL CHANGES DUE TO DAMAGE. 309 enescence affects the tissues of the periosteum and endosteum, as well as the surrounding connective tissue of the fibrous type. In the subsequent differentiation of the granulation-tissue, which in this case is called the " callus," those cells which have been derived from the periosteum and endosteum produce bone, which becomes continuous with the osseous tissue of the fragments and restores the continuity of the broken bone. It is evident that in this case the re- juvenescence of the bone-forming cells has not caused a reversion to an entirely unspecialized type of connective-tissue cell. It is equally evident that in the production of cicatricial tissue the cells of fibrous tissue retain their special formative powers after rejuvenescence. 2. Suppuration. — This is occasioned by the persistent action of a damaging cause which is accompanied by the presence of substances exerting a " positive chemotactic influence " upon leucocytes (/. e., attracts those cells) and at the same time effecting solution of the tissue-elements. In clinical experience nearly all cases of suppu- ration are due to infection with bacteria ; but purulent inflamma- tions of very limited extent may be caused experimentally by chem- ical substances free from micro-organisms. Suppuration does not, however, always follow infection, even by pyogenic bacteria. Sometimes the virulence of the bacteria is too slight for the production of chemotactic substances in sufficient quantity to attract large numbers of leucocytes. Sometimes it is so great that the chemotactic influence becomes " negative " (i. e., repels leucocytes), or the leucocytes are killed before they can collect in sufficient numbers to form pus. The relations between the leuco- cytes and the chemotactic substances are quantitative : if the sub- stances be present in too great dilution, they fail to attract leuco- cytes ; if in too great concentration, they repel them. Nor are bac- teria and their products the only substances that attract leucocytes. Bits of dead tissue may do the same, a fact which would promote their absorption through the agency of the leucocytes. These points will be made clearer if illustrated by an example, for which purpose an infection of the kidney through the vascular system may be selected. If a section be made through the organ so as to include a focus of infection, the bacteria will be found in the bloodvessels. The appearance of the tissues surrounding the ves- sel will depend upon a number of circumstances ; among others, the length of time that has elapsed since the bacteria were brought to the part. In one case the walls of the obliterated vessel and the 310 HISTOLOGY OF THE MORBID PROCESSES. tissues in the vicinity may show chiefly necrotic changes; the tissue will be diffusely stained, the nuclei either unstained, only faintlv tinged, or broken into fragments that take the dye in vari- ous intensities (Fig. 274). Around this necrosed tissue there Fig. 274. Secondary infection of the kidney in a case of erysipelas. (Faulhaber.) a, capillary con- taining streptococci ; 6, renal tubule containing a hyaline cast ; c, renal tubule filled by a deposit of calcareous material. In the neighborhood of the capillary containing the bacteria the tissues have been necrosed, and have become reduced to a granular detritus through the peptonizing action of products formed by the bacteria. More remotely, at the upper left, the cells in the renal tubules are in a state of albuminoid degeneration. In this ease the bacteria are evidently of great virulence ; probably capable of destroying leucocytes that wandered into their neighborhood, through concentration of the poisons produced ; for the section contains no evidence of a round-cell infiltration with emigrated leucocytes. may be a ring of leucocytes, easily identified by their irregularly shaped or fragmented nuclei, which, unless necrosis has taken place, are more deeply stained than the normal nuclei of the surrounding kidney. The central necrosis is due to the poisons that have accom- panied the bacteria at the time of infection or have been subsequently produced by them. Having killed a portion of the tissue through the action of these poisons, the bacteria thrive upon the dead mat- ter and produce fresh poisons, which increase the area of necrotic STRUCTURAL CHANGES DUE TO DAMAGE. Fig. 275. 311 *• *?* ■«$$; ■ iw :■-,;/«/ .;* j* «- ** #■-■■ «>T^ :•••/. ■^••r ■• ,f%? >,'S| *■. id .f;-' ."-'^j i'/'' Jf ^ 9/ ^t v ^Mj£sLoii$& " (..'.. t <* ^f§$«.---- ..'/:^V. ^jfc ■■■«L*»tf* h *. #'■ V -• as* *--■ "T" Beginning abscess -formation in the kidney. (Faulhaber.) The suppurative inflam- mation is due to secondary infection by bacilli carried to the kidney from a phleg- monous inflammation of the neck, a, a, bacilli in the capsule of a Malpighian body, the necrotic glomerulus of which is seen in the upper half of the figure; b, bacilli in the lumen of a convoluted tubule. The epithelial lining of that tubule has been de- stroyed and dissolved ; only three nuclei, almost devoid of chromatin, remaining. The basement-membrane is also partially destroyed, c, beginning abscess-formation in the interstitial tissue between the convoluted tubules. These foci of suppuration are crowded with leucocytes, in some of which the nuclei have become poor in chromatin through the action of the poisons present. Among the leucocytes are a few bacilli, the virulence of which can only be moderate, since comparatively few of the leucocytes are necrotic. Fig. 276. EK $\2?%** :< '>-«*' f® 9 ** Pus from virulent abscess-formation. (Grawitz.) The leucocytes show marked necrotic changes, chromolysis. c, c, well-preserved leucocytes; E. A"., connective-tissue cells from the neighboring granulations ; z, similar cells necrosed. 312 HISTOLOGY OF THE MORBID PROCESSES. action. Toward the periphery of the inflammatory focus these poisons are more dilute, and exert a positive chemotactic influ- ence upon the leucocytes, stimulating their emigration and prog- ress toward the centre of the inflamed area. If they advance too far, however, or the accumulating poisons become too con- centrated, they suffer necrosis or degeneration in the same manner as the tissues of the part. In this way the necrotic process may advance more rapidly than the restricting inflammatory process can cope with it. But to a certain extent the poisons they produce are injurious to the bacteria themselves, so that as they become more concentrated the growth of the bacteria is checked. The injurious influence of the bacteria upon the tissues is also, after a time, miti- gated by the production within the body of chemical substances called " antitoxins," which neutralize the poisons produced by the bacteria. Other substances may also be produced which have a germicidal action. There will come a time, therefore, pro- vided the individual lives, when the productive inflammatory process on the part of the tissues will predominate over the destructive action of the bacteria and confine the poisonous area within a zone of granulation-tissue. This demarcation does not take place in most cases until a collection of pus, an abscess, has been formed in and around the area of necrosis. The appearances are then different, and require a brief description. An abscess or collection of pus within the tissues contains a fluid of serous character, in which there is such a great number of sus- pended leucocytes that they give it a milky or creamy appearance. This liquid is pus (Figs. 275, 276, and 292). The walls enclosing the pus are composed of granulation-tissue infiltrated with emi- grated leucocytes making their way to the fluid contents. The liquefaction of the tissues which makes the central cavity pos- sible is the result of maceration, the disintegrating action of the leucocytes, and, probably in still greater degree, is due to a pep- tonizing action exerted by the bacteria or their products. There is now an antagonistic action between the bacteria and their products and the tissues, in which possibly the phagocytic action of the leucocytes may aid the tissues. The activities of the tis- sues are directed to the formation of cicatricial tissue ; the bac- teria and their products tend to impede those activities or to destroy their results. If the destructive action predominates, the pus increases in amount and " burrows," following the direction of STRUCTURAL CHANGES DUE TO DAMAGE. 313 least resistance, until it is finally discharged along with some of the bacteria and poisons. This frequently brings relief, and the abscess becomes an open Avound, which heals by granulations in the way already outlined. In other cases the conflict between the bacteria and the tissues may be more evenly balanced and the pus confined by granulations, which are injuriously affected on the surface, but progress toward the formation of fibrous tissue in their deeper portions. Such a lining of granulation-tissue is called the " pyogenic membrane " of the abscess. Similar pyogenic membranes are formed on the walls of sinuses resulting from the discharge of an abscess when the infection is still sufficient to prevent the growth of healthy and vig- orous granulation-tissue, or when the burroAving of the pus before its discharge has been so slow that the granulations surrounding the sinus have become organized in their deeper portions and are no longer capable of nourishing young and active tissues at the surface. In such a case curetting of the sinus-wall would remove this imperfectly nourished tissue and promote the development of vigorous granulations. Still another variation of the process is possible when the infec- tion becomes very greatly reduced in virulence or the bacteria die. In this case the granulations grow and obliterate the cavity in case its contents are absorbed, leaving a puckered scar, or its contents may become inspissated through absorption of the serum, and the leucocytes be converted into a cheesy mass by fatty degeneration combined with necrosis ; in which case the resulting mass becomes encapsulated by cicatricial tissue. The resulting nodules are liable to subsequent calcareous infiltration. 3. Fibrinous Inflammation. — This frequently affects the serous membranes, the lung, etc. A case of lobar pneumonia may be selected as a typical example. After a preliminary congestion of the vessels in the Avails of the pulmonary alveoli an exudate, consisting of serum and red cor- puscles, Avith a comparatiA'ely small number of leucocytes, is poured out into the alveoli. Here fibrin is formed, so that the exudate becomes solid (Fig. 268). This constitutes the stage of " red hepatization." This stage gradually passes into that of " gray hepatization," in consequence of an immigration of leucocytes into the fibrinous exudate, the red corpuscles meanAvhile losing their coloring-matter, so that the red color due to them passes into a 314 HISTOLOGY OF THE MORBID PROCESSES. gray (Fig. 272, , c, red corpuscles in various stages of decolorization and disintegration ; D and F make up the exudate upon the pleural surface; lies, exudate in the pulmonary alveoli. first appears as a layer of fibrin upon the surface of the pleura. This may subsequently disintegrate and be absorbed, or granulation-tis- sue may develop from the pleura beneath it and grow into the fibrin, causing its gradual absorption and replacement with fibrous tissue. STRUCTURAL CHANGES DUE TO DAMAGE. 315 In this way a fibrous thickening of the pleura is formed, which remains as an enduring evidence of the inflammation that caused it (Fig. 272). Again, it may happen that the inflammatory process is communicated to the costal pleura where it is in contact with the visceral layer. In this case fibrin is formed on both pleural surfaces, which become agglutinated in case they are in contact. When, in such cases, the interposed fibrin is replaced by cicatricial tissue, per- manent fibrous adhesions between the lung and thoracic wall result. When the exudate contains sufficient serum to prevent the agglutina- tion of the two pleural surfaces such adhesions do not take place, but each pleural surface receives a permanent layer of fibrous thickening. Fibrinous inflammation may affect other tissues than those of the serous membranes (Figs. 278 and 279). Fig. 278. d— Fibrinous leptomeningitis : a, cerebral cortex ; b, torn bloodvessel entering the brain from the pia mater; c, fibrous tissue of the pia mater; d, the same tissue infiltrated with emi- grated leucocytes ; c;, fibrinous exudate in the wide-meshed areolar tissue of the pia mater. 4. Serous Inflammations. — Like the fibrinous, these inflammations are common affections of the serous membranes. Pleurisy is often an inflammation of this sort. The exudation is chiefly serous, of a light-straw color, and either quite clear or containing flakes of 316 HISTOLOGY OF THE MORBID PROCESSES. Fig. 279. Fibrinous leptomeningitis : a, cerebral cortex ; &, serum, with detritus, separating the brain from the pia mater ; c, bloodvessel of the pia mater, the "walls of which are infiltrated with emigrating leucocytes ; d, fibrinous exudate ; e, smaller vessel of the pia. fibrin. Fibrin is also frequently deposited, or rather formed, upon the pleural surfaces; but agglutination of the opposed surfaces, with the formation of adhesions, is prevented by the fluid that keeps them apart. Another common site for serous inflammations is the skin, slight burns causing a serous exudation under or within the epidermis, the horny layer of which is raised to form the cover- ing of a blister. Serous inflammations may also affect other por- tions of the body (Fig. 280). Under the microscope a few leucocytes and blood-corpuscles can be detected in the serous exudate. Some of the leucocytes may be infiltrated with fat-globules, which they have appropriated from the debris of degenerated cells. These drops of fat may be so numer- ous as to obscure the nucleus and completely fill the cytoplasm, dis- tending the cell to fully twice its normal size. These cells have received the name "compound granule-cells" (Fig. 195). When the inflammation affects a serous surface detached and swollen endothelial cells may also be present in the fluid. 5. Catarrhal inflammations are those which affect mucous mem- branes, with the production of a fluid exudate appearing upon their STRUCTURAL CHANGES DUE TO DAMAGE. 317 surfaces. In the exudate, besides the usual constituents, there are desquamated epithelial cells and a variable amount of mucus. Mucus, it will be remembered, is a substance normally secreted upon the mucous membranes, where it serves to protect the underlying cells. When those membranes are irritated the supply of mucus is increased. In catarrhal inflammations it may be so abundant as to Fig. 280. Serous leptomeningitis : n, oedematous fibrous tissue of the pia mater, the fibrous elements of the tissue being separated by the serous exudate ; b, group of leucocytes, probably held together in part by fibrin ; c, granular fibrin and detritus ; 6 and c, and other similar masses, lie in the serum, which occupies the whole field between the visible elements. predominate over the elements of the exudate, so that the fluid appearing on the surface of the membrane has a viscid character. In other cases the mixed secretion and exudate may be muco-serous or muco-purulent (Fig. 281). In catarrhal or broncho-pneumonia the exudate appearing in the alveoli of the lung is of a serous character, with an admixture of desquamated cells from the alveolar walls and a variable number of leucocytes. These sometimes give the exudate an almost purulent appearance. 6. Croupous inflammation is an inflammation of a surface, char- 318 HISTOLOGY OF THE MORBID PROCESSES. acterizerl by the formation upon it of a " pseudomembrane " com- posed chiefly of fibrin. 7. Diphtheritic inflammation is a term usually applied to inflam- mation affecting the tissues underlying a free surface. It is char- acterized by local death of the superficial portions of those tissues with an accompanying coagulation (Fig. 263). The result is the Fig. 281. !•>«;. \V 3*,' -.'■f-r^;: *&;•*• 6 — Catarrhal bronchitis: a, areolar tissue of the submucosa, infiltrated with serum and leuco- cytes; 6, alveolus of a mucous gland, infiltrated at the periphery by leucocytes. The epithelium is undergoing colliqxiative necrosis, and in the centre of the lumen are a few leucocytes with fibrin, c, c', bloodvessels, c 7 shows an infiltration of the wall by emi- grating leucocytes, d, muscularis mucosae ; e, subepithelial areolar tissue of the mucous membrane, infiltrated with serum and leucocytes ; /, columnar epithelium of the surface in a state of colliquative necrosis ; g, exudate within the bronchus. In this portion of the bronchus the destructive processes are so acute that the epithelium is destroyed, instead of stimulated to the production of excessive mucus. formation of a membranous mass of dead tissue closely adhering to the tissues beneath, a so-called " true membrane/' in contradis- tinction to the "false membrane." of croupous inflammation. This membrane is subsequently separated from the underlying tissues by the formation of granulations, leaving an ulcer. 8. The "infective granulomata," such as tubercle, gumma, and the STRUCTURAL CHANGES DUE TO DAMAGE. 319 nodules of leprosy and glanders, are forms of subacute inflamma- tion which owe their peculiarities to the infections that occasion them. The tubercle, caused by the presence of the tubercle bacil- Fig. 282. Early stage of experimental tuberculosis ; cornea of rabbit. (Schieck.) Five days after inoculation. Rejuvenescence and beginning degeneration in fixed cells of the fibrous tissue, a, karyolysis in a cell affected by a group of tubercle bacilli within the cyto- plasm ; b, karyokinetic figure in another cell. lus, is the most common of these inflammations and may be taken as a type of the whole group. The tubercle bacillus does not always produce the little in- Fig. 283. « €> Early stage of experimental tuberculosis ; cornea of rabbit. (Schieck.) Ten days after inocu- lation. Beginning of a tubercle. The " epithelioid " or young connective-tissue cells are masked by the presence of leucocytes with denser nuclei, which have been attracted by the chemotactic (positive chemotaxis) influence of the materials accumulating in the inflamed focus. flammatory nodules called " tubercles." It sometimes occasions a suppurative inflammation of sluggish type, forming "cold ab- scesses/' or purulent inflammations of mucous membranes. It .">20 HISTOLOGY OF THE MORBID PROCESSES. may also cause sero-hsemorrhagic exudations from the serous membranes — c. ;/., the pleura; but the most characteristic tissue- reaction due to its presence is the formation of the tubercle. This is the result of a rejuvenescence of the connective-tissue cells, without any preceding exudation, and an attempt at the pro- duction of granulation-tissue around the bacilli (Figs. 282 and 283). These multiply so slowly that they and their products exert merely an irritation on the cells of the tissue, stimulating tlicin to reproduce, but they do not usually cause the growth of new bloodvessels, so that in the majority of eases the granulation-tis- sue is not vascularized. Furthermore, as they increase in number the bacteria cause degenerative and necrotic' changes in the cells that have been produced, and, as their products increase in amount, the cells in the centre of the focus of inflammation are destroyed (cheesy degeneration, p. 274), while those at the periph- ery multiply, causing an increase in the size of the inflamma- tory nodule or tubercle. The multiplication of the cells is often hindered to a certain extent by the poisons present ; the nuclei divide, but the protoplasm fails to undergo a corresponding di- vision. Tn this way multinucleated cells, called "giant-cells," are produced. As the result of these processes a developing tubercle presents the following appearances under the microscope. In the centre is a mass of cheesy matter, composed of fine granules of fat, albuminoid material, and fragments of nuclei, the result of degenerative and necrotic changes caused by the bacterial poisons. Around this mass is a zone of rather large "epithelioid" cells, which belong to the granulation-tissue, and among which there may be a variable number of emigrated leucocytes, probably attracted by the necrosed tissues in the centre. Also, near the centre or in the granulation- tissue, a few giant-cells may be present ; but they are not invariably found, nor is their presence a conclusive sign that the process is tubercular (Fig. 284). The ultimate outcome of the process varies in different cases. The inflammatory reaction may overcome the infection, encapsulat- ing the nodule with a dense cicatricial tissue; or the infection may conquer ; bits of the cheesy matter containing tubercle bacilli may then find entrance into the lymphatic circulation and he carried to the neighboring lymph-glands, establishing in them new foci of tubercular inflammation, or tubercle bacilli may get into the blood- () STRUCTURAL CHANGES DUE TO DAMAGE. 321 vessels and curry the infection to all parts of the body, occasioning general tuberculosis. The poisonous products of the tubercle bacilli are absorbed hit the general system, producing disturbances of nutrition, emaciation, and fever. Old encapsulated tubercular products are prone to calcareous infiltration, but, even after prolonged encapsulation, Fig. 284. .Miliary tubercle ; lung of a horse. (Birch-Hirschfeld and Johne.) Cheesy degeneration has only just begun in the centre of the focus of inflammation, where the nuclei of epithe- lioid cells and leucocytes are still visible. At the periphery of the tubercle is a zone of round-cell nr leucocytic infiltration. Three giant-cells, with peripheral nuclei, occupy intermediate positions; around the tubercle are the infiltrated walls of pulmonary alveoli. the tubercle bacilli which have been imprisoned may retain their vitality, and, if for any reason the poorly nourished capsule suffers in its integrity, these old nodules may become the source of fresh infection. This is a not uncommon result of some acute disease like scarlet fever, tvphoid fever, or influenza, convalescence from those diseases being followed by the development of tuberculosis spring- ing from an old and long-dormant tubercular infection. In the lungs the tubercles, as they increase in size, involve the walls of the alveoli or the bronchi, and when the cheesy matter 21 322 HISTOLOGY OF THE MORBID PROCESSES. escapes into the alveoli or bronchi cavities are produced. The proc- ess rarely remains a purely tubercular one in the lungs. The con- ditions there (exposure to inspired air) are favorable to a mixed infection with pyogenic bacteria, which hastens the destruction of the pulmonary tissues inaugurated by the tubercle bacillus. Isolated tubercles, such as have been described, are not infre- quently met with ; but it is more usual to find a number of such nodules in close aggregation, each starting from a distinct focus of infection. As these enlarge, their peripheries coalesce, and finally their cheesy centres meet and blend. Meanwhile fresh young nodules are formed around the older mass, and thus the tubercular disintegration of the tissues spreads. It is for this reason that tubercular ulcers — v. g., of the intestine — have swollen and under- mined borders (Fig. 285). Fig. 285. Tubercular ulcer of the intestine. (Kaufniann.) The cavity of the ulcer was formed through disintegration and removal uf the cheesy matter formed in the earlier tuber- cles. Now the base of the ulcer is formed by necrosed and cheesy material, beneath which eight or nine distinct tubercles are distinguishable, those in the centre extending into the muscular coat of the intestine. The infection has also extended into the lymph- atics beneath the serous coat, where three tubercles can be seen. The other granulomata have peculiarities due to their special causes, which are pretty clearly defined in typical cases ; but, as in tuberculosis, these inflammations may in certain instances be structurally indistinguishable from those due to other causes. Chronic Inflammation. A consideration of the infective granulomata makes the fact clear that inflammation may occur without the production of a distinct exudate, the damaging cause merely exciting the tissues to prolifer- ation ; but in that group of inflammations the excitation of the tis- sues was sufficiently intense to occasion the development of a tissue closely resembling the granulations of acute inflammation. For this reason they were designated as Nubacutv inflammations. There is another group of inflammations in which the irritation of the tissues is not sufficient to induce a rejuvenescence of the cells in such a pronounced degree as to cause their reversion to a STRUCTURAL CHANGES DUE TO DAMAGE. 323 comparatively undifferentiated condition. No granulations are, therefore, produced, but the cells are simply stimulated to a forma- tive activity that is abnormal to the part. This is the group of chronic inflammations, of which three or four examples will be cited. Chronic periosteal inflammation may be induced by a number of damaging causes of slight intensity, but repeated application. The response which the cells of the periosteum make to this irritation is a revival of their formative activity and the production of bone, which forms an " epiphyte," or other osseous excrescence, apparently springing from the surface of the older bone. Similar new-forma- tions of bone may take their origin from the endosteum, forming Fr Cirrhosis of the liver : chronic interstitial hepatitis. (Kaufmann.) a, lobules of the liver; ft, increased interstitial fibrous tissue, the result of the inflammatory process; c, collec- tion of nuclei in the fibrous tissue, shewing that the process is still in progress ; d, thick- ened eapsule of the liver. lavers that encroach upon the lumina of the Haversian canals or the medullary cavity of the bone. These deposits are more diffuse than those springing from the external surface of the bone, probably because they arise as the result of a more widespread irritation, such as the presence of some noxious substance in the circulation, and not from a localized point of irritation. Another example of this group is presented by cirrhosis of the liver, 324 HISTOLOGY OF THE MORBID PROCESSES. selected from among the chronic interstitial inflammation* that may affect any of the organs of the body. In hepatic cirrhosis there is a redundant production of fibrous tissue around the branches of the por- tal vein, and, therefore, appearing between the " lobules " of the liver (Fig. 280'), This has the same tendency as other cicatricial tissue to contract, and that contraction causes atrophy of the hepatic cells through the pressure it exerts upon them. There may 1 >e another cause for this atrophy of the liver-cells, which will be more comprehensible after considering the probable etiology of the interstitial inflamma- tion itself. This appears to be caused by the absorption of irritating substances from the digestive tract, which are carried in most con- centrated form by the portal vein to the liver. Here they stimulate the cells of the connective tissue to produce fresh fibrous tissue around the branches of that vessel. But it is quite possible that those same substances may act injuriously upon the parenchymatous cells of the liver, impairing their nutrition and rendering them especially liable to atrophy under the increased pressure from the fibrous tissue in their neighborhood. While the interstitial inflammation is in progress the connective tissue of Glisson's capsule appears not only increased in amount, but more highly cellular than normal. This is due in part to a multiplication of the fixed cells of the fibrous tissue, in part to a round-cell infiltration — /. <•., an immigration of leucocytes. This immigration is more abundant in some cases than in others, as would be expected, since the process must be subject to exacerbations, due to fluctuations in the amount of the irritating substances brought to the liver. In fact, we should hardly expect to find a sharp division between the slowest chronic inflammation and such inflammations as approach the character of a subacute manifestation of the same process. A third example of the chronic inflammatory process may be found in the reaction of the tissues around the necrotic mass result- ing from bland embolism. Suppose one of the vessels of the kidney to be plugged by an aseptic body. The tissues normally supplied with blood through that vessel will die (Fig. 293). But the presence of this dead tissue, although it contains no micro-organisms, acts as an irritant upon the surrounding tissues, which respond bv the produc- tion of a capsule of fibrous tissue. The necrosed tissues may remain within this capsule, or they may be absorbed, in which case the capsule shrinks to a puckering mass of dense fibrous tissue. ZiTIU'lTI'HAL ('HASHES DUE TO DAM All K. ;i2o In like manner a non-infectious foreign body may become encapsu- lated within any of the tissues of the body. Still another example of chronic interstitial inflammation appears to be furnished bv eases in which the parenchyma has sull'cred atrophy or some other form of destruction, and the loss is made good by the production of fibrous tissue without a precedent forma- tion of granulations. In embolism of a branch of one of the coronary arteries supplying the heart-muscle the destruction of the muscle-tibres seems to stimulate (lie formative activities of the cells of the interstitial fibrous tissue. The deduction that the production of fibrous tissue is the direct result of a loss of parenchyma is, how- ever, not (piite clear, for the stimulus to tissue-production may Fia. 2S7. Chronic interstitial inflammation. Karly slai;e of productive interstitial neuritis. (Nnu- worek and Itarth.) Theseetiou is from the anterior root of a lumbar nerve. It repre- sents a. number of apparently normal medullated nerve-fibres in eross-seetion, with proliferation of the eel Is oi'Ihe eudoneurium, as is evideneed by the abnndanee of mielei in that tissue. result from the unusual strain brought upon the part of the heart "which is deprived of the usual support of muscular tissue. It niav be that other cases in which a loss of parenchyma is replaced bv fibrous tissue an- also not due to stimulation of fibrous-tissue production because of that loss, but are to be explained in a man- ner analogous to the explanation of cirrhosis already oll'ercd. Further examples oi' interstitial inflammations are shown in Figs. •2S7 and '2SX. 326 HISTOLOGY OF THE MORBID PROCESSES. From the examples that have been given it will be noticed that, amid all its protean manifestations, the inflammatory process is fun- Fig. 288. a b' b I I I MP » .<<$„ '■ :,:■- &<*F aC.f^ " : .®Z 9 . V ® Chronic interstitial myocarditis, late stage : a, dense fibrous tissue, the final result of the interstitial inflammation; b, &', 6", atrophied cardiac muscle-cells; b', vacuolation of a less atrophic evil ; b", section showing anastomotic branch joining two cells ; c, partially obliterated bloodvessel. damentally the same, but susceptible of many variations ; and when the conditions arc not too adverse it leads to a removal of the cause of an injury and to a more or less complete repair or patching of the tissues that have been damaged. III. INCIDENTAL CONSEQUENCES OF DAMAGE AND INFLAMMATION. The damage and ensuing inflammation affecting a part of the body not only occasion changes in the structure of that part, but also, through those changes, very frequently cause morbid conditions in remote parts. It will be impossible to enumerate all the possi- bilities in this connection, but a few examples will suffice to show their importance. It is obvious that chronic interstitial hepatitis (Fig. 286) must affect the circulation in the portal system of vessels. The inflammatory fibrous tissue formed between the lobules of the liver, and, therefore, around the portal vessels within that organ, pos- sesses the same tendency to contract after its formation that is mani- fested by cicatricial tissue of more acute inflammations, though perhaps STRUCTURAL CHANGES DUE TO DAMAGE. 327 in less degree. This contraction would suffice to compromise at least the smaller branches of the portal vein entering the lobules, so as to obstruct the current of blood flowing- through them. The result is an increase of pressure in the portal circulation and the production of passive hypersemia or congestion of the organs in which the portal radicles are situated. This passive congestion results in a dilatation of the vessels in Fig. 289. Brown induration of the lung, the result of chronic passive congestion caused by valvular disease of the heart : a, small radicle of the pulmonary vein, dilated and filled with blood ; 6, alveolar wall in cross-section, thickened and containing an abnormal number of nuclei (evidence of an increase of tissue, a chronic interstitial pneumonia) ; c, surface- view of an alveolar wall, showing similar abundance of nuclei and a dilatation of the capillaries, evidenced here and elsewhere in the section by a double row of corpuscles in a capillary ; d, cavity of an alveolus ; e, alveolus containing serum, red corpuscles, and leucocytes, and also large pigmented cells. These are chiefly leucocytes which have taken up pigment from the red corpuscles that have disintegrated— phagocytes. Some of these large cells may be desquamated epithelial cells from the alveolar walls, in a swollen and degenerated condition. The presence of serum is demonstrated by the fact that the cells in the alveolus are not lying aaain't the alveolar walls. The escape of the blood-corpuscles from the capillaries is a result of the sluggish circulation. those organs and a thickening of their walls, and also frequently induces a chronic interstitial inflammation. It may also so impede the lymphatic circulation and impair the nutrition of the vascular 328 HISTOLOGY OF THE MORBID PROCESSES. walls as to give rise to an excessive transudation of serum and occasion oedema and ascites. Similar chronic passive hyperemias may follow those inflam- matory lesions in the valves of the heart which cause either agglutination and permanent adhesions of the valvular curtains, stenosis; or a contraction of one or more of those curtains, so that their proper closure is prevented, incompetency. In either case the circulation is impeded and the flow of blood from the organs behind the lesion interfered with (Fig. 289). Haemorrhage is another of the frequent results of damage. It may be recognized by the presence of blood outside of the vessels. This blood at first contains the red and white corpuscles in their normal proportions, but after a lapse of time the clot which forms becomes infiltrated with leucocytes as the expression of an inflam- matory reaction induced by the extravasated blood. Subsequently the blood disintegrates, productive inflammation is induced, and the lesion heals, with the production of a scar. This is often colored brown or gray, from the presence of pigment derived from the haemoglobin of the red blood-corpuscles. This pigment may be in the form of reddish-brown rhombic crystals, or granules, of hrernatoidin ; or it may take the form of small granules of hemo- siderin. The latter substance contains iron, from which the former is free, and under the action of sulphuretted hydrogen produced by decomposition may give rise to sulphide of iron, changing its brown color to black, and the color of the pigmentation from a brown to some shade of gray. Haemorrhage may be among the direct results of damage to the tissues, or it may follow necrotic changes in the vascular wall. This is a not infrequent occurrence in virulent forms of infection, and results in the formation of small, punctiform hemorrhages ; for the vessels necrosed are usually of small calibre and surrounded by tissues sufficiently firm to check the flow of blood under the slight pressure within those vessels (Fig. 290). But more copious hemorrhages may occur in the course of slowly progressing infec- tions, notably in pulmonary tuberculosis. It will be remembered that the walls of the larger vessels are composed of a dense fibrous tissue rich in elastic fibres (Fig. 97). Such a tissue resists the necrosing action of tuberculosis for a longer time than the more succulent tissues of the lung. It therefore occasionally hap- pens that a cavity may be formed by the destruction of the pul- STRUCTURAL CHANGES DUE TO DAMAGE. 329 monary tissue, and that through this cavity, or within its walls, a pervious vessel of considerable diameter may take its course. After a while the wall of this vessel may become sufficiently destroyed to yield before the pressure of the blood within it ; rupture may then take place, with the effusion of considerable blood, haemoptysis. In many cases, however, such a result is prevented by the forma- tion of a clot (thrombus) within the vessel before erosion of its wall has gone far enough to threaten rupture. Thrombosis. — This term is applied to the formation of fibrin within the circulatory system during life. It may take place when Fig. 290. •w Hsemorrhage in the kidney following general infection. (Tizzoni and Giovannini.) The haemorrhage has taken place within the capsule of a Malpighian body and part of the extravasated blood has passed into the corresponding uriniferous tubule. The glomer- ulus has been compressed (to the right), an occurrence which probably checked the haemorrhage. The tissues of the glomerulus and of the neighboring tubules are necrotic. the circulation in a particular vessel or in a portion of the heart is sufficiently sluggish to permit leucocytes and, perhaps, blood-plates to collect and remain in one place long enough for their disin- tegration to begin. The elements required for fibrin-formation are then set free and thrombosis results. In this way thrombi may form between the columnfe carnese in marantic conditions, behind the curtains of venous valves, or in the lumina of dilated veins within the pelvis. Thrombosis may also occur as the result of a roughening of the intima of a vessel or its mechanical destruction, as in the tving or crushing of a vessel. Thrombosis may be the result of disease of the vessel-wall, caused by infection or malnutrition. The affection of the veins known as septic thrombophlebitis may be selected as one of the more impor- tant acute lesions of the vessels. This is caused by an infection of 330 HISTOLOGY OF THE MORBID PROCESSES. the vascular wall, which eventually reaches the intima. Here a fibrinous inflammation, analogous to that of a serous membrane (p. 313), is induced. The roughness of the intima so occasioned induces the formation of a thrombus (Fig. 291). Meanwhile the Fig. 291. t MM ti ->--;%l i:W.- vc;;-> Thrombophlebitis, incident to erysipelas of the arm. (Kaufmann.) The thrombus occupies about two-thirds of the lumen of the vein, which is surrounded by areolar tissue infil- trated with serum and leucocytes. septic process in the wall of the vessel progresses and extends into the thrombus, which is softened. The rate of softening may now exceed that of thrombus-formation, in which case the thrombus is broken up, and particles containing some of the bacteria occasion- ing the inflammation gain access to the venous circulation (see Embolism). Embolism. — The obstruction of a vessel by a foreign body brought from a distance by the circulating blood is called embolism. The foreign body, or embolus, is usually a small mass of fibrin ; but it may be air, fat (derived, for example, from the medulla of a fractured bone), a calcareous fragment, or a particle of tissue. With the exception of the branches of the portal vein, the vessels obstructed by an embolus are arterial. The results of embolism will depend, first, upon the anatomical distribution of the vessel plugged, whether there are anastomotic branches of considerable calibre beyond the site of the obstruction ; second, upon the nature STRUCTURAL CHANGES DUE TO DAMAGE. 331 of the embolus, whether it contain pathogenic bacteria or not. In the former case the embolus is called a septic, in the latter a bland, embolus. In septic embolism an acute inflammation, similar to that at the Fig. 292 Metastatic abscess in the heart, due to septic embolism. (Birch-Hirschfeld.) The abscess- cavity contains red blood-corpuscles and leucocytes with fragmented nuclei. The muscle-fibres within and near the cavity have been killed and many of them dissolved. site of the original lesion, is induced by the bacteria brought with the embolus. If the original inflammation was suppurative, ab- Fig. 293. Experimental anaemic infarction of the kidney : rabbit. (Foa.) a, necrotic tissue formerly supplied by the artery obstructed ; b, zone of affected tissue surrounding the infarct. In this zone the renal tubules contain hyaline casts, and their lining epithelium shows an evanescent tendency to proliferate, some of the cells containing karyokinetic figures, c, normal renal tissue. scesses, called metastatic abscesses, are formed around each septic embolus (Fig. 292). In bland embolism, when there are ample anastomoses between the vessel plugged and other vessels beyond the site of the embolus, 332 HISTOLOGY OF THE MORBID PROCESSES. no serious result follows. Thrombosis takes place around the em- bolus, but the circulation beyond it is maintained through the anas- tomotic vessels. If, however, the anastomoses are not sufficient to maintain the nutrition of the tissues normally supplied by the ob- structed vessel, those tissues suffer necrosis (Fig. 293). Such a mass of necrosed tissue is called an "infarct." Infarcts are divided into amende and hemorrhagic infarcts. The former occur when the tissues are entirely deprived of blood by embolism (Fig. 293) ; the latter take place when, through innutri- tion of the vessels in the part affected by infarction, blood, derived from the veins or through capillary or other fine anastomoses, is permitted to pass into the interstices of the necrosed tissues. These then appear surcharged with blood. The most striking example of hemorrhagic infarction is that following bland em- bolism of a branch of the pulmonary artery (Fig. 294). Fig. '.>9t. ( \ c ^%Mk& lll§ '^^sSsk "•: ■'..','. ■ ;■■■ P0mM «H '' ' i ' ''•' 'Cviijft j|ll§|f§p8 £: ^ - .„ m \y-^(i--^^^^^^ ^^poz-Ji^ rgC • - Y£§ section contains a portion of the plugged vessel beyond the site of the embolus. It and the pulmonary alveoli arc filled with blood, which, in the latter, has passed through the capillary walls, rendered per- vious by malnutrition. This blond may be derived from the pulmonary vein and also from the bronchial artery, which communicates with the capillaries of the alveolar walls. Phagocytosis. — In the preceding pages incidental mention has been made of the ability of leucocytes and other amoeboid cells to incorporate within their cytoplasm particles of foreign matter with which they may come in contact. Such cells within the body are called "phagocytes" (devouring- cells). It was at one time thought that these cells had much to do with the killing and destruction of pathogenic bacteria and other organisms that might gain access to the system ; but it is now believed that such is not the case. STRUCTURAL CHAXGES DUE TO DAMAGE. 333 Phagocytes do incorporate bacteria ; but if those bacteria are viru- lent, the phagocyte either refuses to take them within its cytoplasm, or, after doing so, suffers degeneration or necrosis. It has no pecu- liar immunity against the action of the bacteria. On the other hand, it has been shown that the fluids of the body are capable of diminishing the virulence of bacteria or of killing them. It often takes some time for the production of the substances that have this effect, and their elaboration is frequently too tardy to check the destructive action of the bacteria. But upon the surface of granu- lations, from which absorption is slow or does not take place, the effects of the tissue-fluids have been studied and an attenuation of bacteria (decrease in their virulence) observed. These attenuated Fig. 295. Phagocytes from granulations infected with virulent anthrax bacilli. (Afanassieff.) a, thread of bacilli, partly within and partly outside of a phagocyte. Both portions show a vacu- olation of the bacilli, indicative of their degeneration, d, thread almost entirely incor- porated. Within the cell the incorporated bacilli lie in vacuoles in the cytoplasm ; prob- ably digestive vacuoles. In b and e similar appearances are presented, c, degenerating thread of bacilli from the fluid of the granulations. Vacuolation has also taken place in this thread, showing that the fluids of the granulations have a destructive influence upon the bacilli. bacteria may be taken up by phagocytes with impunity and subse- quently digested within their cytoplasm (Fig. 295). The digestion and removal of degenerated or dead materials appear, then, to be the useful role played by phagocytes. They appear to be the active agents in the absorption of organic frag- ments, such as fibrin, macerated necrotic tissue, etc., which may be present in the tissues of the body (Fig. 296). The majority of phagocytes are probably leucocytes, identical with 334 HISTOLOGY OF THE MORBID PROCESSES. Fig. 296. Phagocytes from aseptic granulations. (Nikiforoff.) C, phagocytes with pseudopodia ; E, without pseudopodia ; F, proliferating, the daughter-nuclei in the spirem phase of karyo- kinesis; A, B, D, with leucocytes, fragments of tissue, and red corpuscles in their cyto- plasm. those in the blood and lymph ; ' but it is possible that young con- nective-tissue cells, which are believed to possess the power of amoe- boid motion, may sometimes play the part of phagocytes. IV. REGENERATION OF THE TISSUES. Frequent reference has been made to the power possessed by many cells to restore or regenerate structures that have been dam- aged by influences causing either necrosis or degeneration. The ability to effect this restoration varies greatly in the cells of different tissues, being, in general, inversely proportional to the degree of specialization to which they had attained at the time the damage took place. We must, therefore, consider this process in the dif- ferent tissues separately, after taking a general survey of the facts that apply to all cases of regeneration. It is needless to say that a cell which has once become necrotic is incapable of restoration ; but if the nucleus be sufficiently pre- served and enough cytoplasm be left after degenerative changes have come to an end, both those cellular constituents may take up nourishment and regenerate the parts destroyed. When whole masses of tissue have been killed, but some of the same form of tissue retains life and continuity with the necrosed portion, the dead tissue may be more or less completely replaced by tissue 1 The polynuclear neutrophile leucocytes are those which most frequently act as phagocytes. STRUCTURAL CHANGES DUE TO DAMAGE. 335 of new formation springing from the living portion. If this takes place, the cells of the latter portion multiply and reassume those formative activities that the)' possessed during the develop- ment of the tissues in earlier life. The division of the cells al- ways takes place by the indirect method, that of karyokinesis. We must not, however, assume that because the cells of a tissue may, under the influence of damaging agents, contain karyokinetic figures, they must necessarily possess the power of regenerating lost por- tions of tissue. More than mere observation of those figures is re- quired to establish that fact. Such figures are occasionally met with in the ganglion-cells of the central nervous system, and they show that the nuclei of those cells retain, at least to a certain extent, the power of division. But this by no means implies that new ganglion- cells, capable of full functional activity, can be produced by the division of an adult nerve-cell, and, as a fact, such an occurrence Fig. 297. Fig. 298. Phases in the regeneration of the gastric mucous membrane; dog. (Griffini and Vassale.) a, regenerated columnar epithelial cells covering the base of the wound : b, c, karyokinetic figures indicative of proliferation. does not appear to take place. In Fig. 293, zone 6, karyokinetic figures are seen in the renal epithelium ; but it is doubtful whether they signify the beginning formation of new renal tissue to replace 336 HISTOLOGY OF THE MORBID PROCESSES. that killed in the anaemic infarct. Such a replacement does not take place in the kidney, but a scar of fibrous tissue is formed around or in place of the necrosed mass. The karyokinetic figures, then, simply demonstrate a tendency toward cell-division, and fur- ther observations are necessary in order to determine the signi Seance of that tendency. 1. Epithelium. — The regenerations of which epithelium is capable are very extensive and perfect. In some forms of epithelium — e. g., the stratified variety and that found in sebaceous glands — the regenerative process is a part of the functional activity of the tissue. After wounds of the skin the epithelium forming the epi- dermis regenerates a new epidermis for the injured area. In this case the epithelial layer, provided the wound be extensive, is rela- tively thin and of low vitality. This is not because the epithelial regeneration was imperfect, but because the nourishment it receives from the underlying cicatricial tissue is deficient. There is in this case a lack of coordinate development in the regenerations effected by the epithelium and underlying fibrous tissues. Remarkable ex- amples of a more perfect coordination are exhibited in the regen- eration of glands (Figs. 297, 298, and 299), where the regenerating epithelium and fibrous tissues appear to cooperate in the restitution of lost glandular structures. The complicated glandular structure of the liver is also capable of regeneration when a portion of that organ has been removed under aseptic precautions (Fig. 300). Where, however, the de- struction is due to damage exciting acute inflammation it is doubt- ful whether any regeneration is possible, owing either to the inju- rious action upon the cells, or to the hindrances interposed by the regenerating portions of fibrous tissue in the neighborhood. 2. Endothelium. — That endothelium is capable of regeneration is shown by the formation of young bloodvessels during the develop- ment of granulation-tissue (Figs. 270 and 271). 3. Fibrous Tissue. — A mode of regeneration of this tissue has been described in the article on inflammation, and is illustrated in Figs. 269 and 270. This tissue, when fully developed, differs from nor- mal fibrous tissue in its density and freedom from bloodvessels (Fig. 273). The regeneration of a tendon severed under aseptic precautions results in a much more perfect restitution of the normal structures. Here the cut ends of the fibre show softening, swelling, and final disintegration of the intercellular substance. Some of the cells are ftf-^Sfe^ STRUCTURAL CHANGES DUE TO DAMAGE. 337 Fig. 300. -4 ^ Section of regenerating liver, (v. Meister.) also affected by a degenerative process; but others rejuvenate, mul- Fig. 301. i-Si-'-^ /' CI Phases in the regeneration of a tendon ; guinea-pig. (Enderlen.) Fig. 301.— Two days after section : a, swollen intercellular substance ; &, karyolysis ; c, d, leu- cocytes; e, karyokinesis. Fig. 31)2.— Seven days after section : a, nucleus of young connective-tissue cell ; b, karyoki- nesis ; c, intercellular substance of new formation. tiplv, and eventually produce a highly cellular tissue, which devel- ops into tendinous fibrous tissue (Figs. 301, 3U2, and 303). 338 HISTOLOGY OF THE MORBID PROCESSES. 4. Bone. — When a piece of bone dies fresh bone is produced through a rejuvenescence of the formative activities of the periosteum (or endosteum). While this new formation of bone is in progress the dead bone is removed by phagocytes, which are usually multi- Fig. 303. Phase in the regeneration of a tendon; guinea-pig. (Enderlen.) Seventy days after sec- tion. The tendon is still rather highly cellular, but its structure is, in the main, fully restored. At the top of the figure is the cross-section of a blood-vessel. nucleated, and have received the name <: osteoclasts" (bone-breakers), in contradistinction to the bone-forming cells of the periosteum, which are known as "osteoblasts" (bone-builders) (Fig. 304). Ik -sp Regeneration of bone. (Barth.) ill;, fragments of necrotic bone; i~, osteoclasts; o, osteo- blasts; 11; , bone of new formation ; g, bloodvessels ; nk', lamina of dead bone, (sp, acci- dental crack in the section.) 5. Cartilage. — This tissue is capable of only a limited and imper- fect regeneration. Defects in cartilage are usually made good by STRUCTURAL CHANGES DUE TO DAMAGE. 339 the development of fibrous tissue, which may become modified into adipose tissue, or by bone-production if the damage causes a re- juvenescence of periosteum or endosteum. 6. Smooth Muscular Tissue. — Non-striated muscle-cells are capa- ble of multiplication, but in inflammatory conditions the tissue of the media of the vessels does not appear to keep pace with that of the intima in the production of new bloodvessels. The latter, therefore, usually lack a muscular coat and are thin-walled (Fig. 272). In the uterus and other situations smooth muscle-cells may multiply and occasion a hyperplasia of the tissue. This appears, however, to be in response to a functional demand, rather than one Fra. 305. Fig. 306. Fig. 305.— Karyokinetic figures in smooth muscular fibres. (Busachi.) Fig. 306.— Regeneration of a striated muscle-fibre. (Kirby.) a, remains of the old contractile substance ; b, rejuvenating cytoplasmic fragments, with their nuclei ; c, similar fragment containing a bit of old contractile substance and a nucleus in karyokinesis, d. of the results of damage : a functional hyperplasia. Karyokinetic figures have been observed in smooth muscle-cells after damage, but they do not lead to a restoration of the original tissue, which heals with the formation of a scar (Fig. 305). 7. Striated Muscle. — When a striated muscle-fibre undergoes 340 HISTOLOGY OF THE MORBID PROCESSES. partial degeneration the cytoplasm around the nuclei that have been preserved may increase in amount, the nuclei may divide, and a multinucleated cytoplasmic mass result from the union of these rejuvenated portions. From this mass new contractile substance is then elaborated. This process results in regeneration of the particular fibre. It is still a question whether new striated muscle- fibres are produced in consequence of regenerative processes follow- ing damage. Wounds of voluntary muscles heal through the formation of a cicatrix (Fig. 306). 8. Cardiac Muscle. — Karyokinetic figures have been observed in the cells of the heart-muscle, but they do not appear to lead to re- generation of that tissue, which heals with the production of scar- tissue when wounded. 9. The Nervous Tissues. — Ganglion-cells have not been observed to rejuvenate so as to produce fresh nerve-cells ; but if the cell-proc- ess forming part of a nerve is severed from the cell without serious damage to the cell-body, a new process or nerve-fibre is developed Fig. 307. KH KZ KR K- B KS Longitudinal section of a regenerating nerve. (Stroebe.) N, nerve ; P, perineurium, con- taining more cells than normally ; KZ, phagocytes, containing globules of myelin from the medullary sheaths of degenerated fibres ; K, nuclei of proliferated cells of the neurilemma; F, young axis-cylinders; KS, points showing the relations of the nuclei and young nerve-fibres ; B, bloodvessel in the perineurium. (Fig. 307). The cells of the neuroglia are, on the other hand, capable of regenerating that tissue. In this respect the neuroglia resembles the interstitial tissue of other organs than those of the central nervous system, often increasing in amount when there is a diminution in the bulk of the parenchyma, due to disease. CHAPTER XXV. TUMORS. It will promote clearness of conception if the term tumor is restricted to abnormal masses of tissue produced without obvious reason and performing no function of use to the organism. In the introductory chapter an attempt was made to show that under normal conditions the parts of the body develop in an orderly manner, which fits them for the performance of work useful to the whole organism, as well as for maintaining their own nutrition and structure. It was also pointed out that parts of the body, when occasion arises, frequently fulfil what appear to be their duties to the whole body, even if their own nutrition or structure suffers in consequence. From these observations we must conclude that throughout the life of the individual each part is controlled in its activities by influences having direct reference to the well-being of the whole body. Those influences control not only the functional activities of the tissues after the body has reached the adult state, but also control or guide the activities of the cells elaborating the body during development. The nature of those influences and the mechanism of their control are unknown to us. We are ignorant of any reason why the tissues of the body should develop to a cer- tain point and then have their nutritive and formative activities restricted to a maintenance of the structures then existent. We attribute these phenomena to the force of heredity, but the expla- nation is incomplete, for that term merely expresses the fact that the offspring of an individual develops into a likeness to its parent. In the development of tumors these guiding or controlling influ- ences are in abeyance, sometimes in greater, sometimes in less de- gree. The tissues do not grow to meet a functional demand imposed upon them by the needs of the body, as appears to be invariably the case in the increase of tissue during the development of the indi- vidual. Instances of growth bringing about such adaptation to altered demands occur after the body has attained full development, 341 342 HISTOLOGY OF THE MORBID PROCESSES. but they are characterized as functional hyperplasia or hypertrophy, not as tumor- formation, and are arrested when the needs giving rise to them are met. This limitation of growth does not hold in the case of tumors. Our knowledge of the normal forces guiding and restricting the development of the tissues being so deficient, how can we expect to understand the causes underlying the development of tumors? The marvel is not that certain cells should occasionally continue to mul- tiply and exercise their formative powers without reference to the needs of the whole body. The fact that such occurrences are so rare awaits explanation. Familiarity with what is usual is apt to blind us to the fact that it is not explained, and when our atten- tion is directed to what is unusual we ask an explanation of the ex- ception. A knowledge of the etiology of tumors appears to await the acquisition of a deeper insight into the nature of hereditary transmission and of the conditions which that transmission ordi- narily imposes upon the tissues throughout the life of the individual. Tumors arise from the cells of pre-existent tissues. The fact that those cells in producing a tumor form a tissue which is functionally useless is evidence that the usual guiding influences mentioned above no longer completely control their activities. The degree in which that control is lost is, however, by no means the same in all cases of tumor-production. Sometimes the tissues of the tumor attain nearly if not quite the complete structural differentiation pos- sessed by the tissue in which it found origin. In such cases only that degree of normal control which has reference to function appears to be abolished, the cells retaining their special formative activities in nearly full measure and producing a tissue resembling the parent tissue. Such tumors may be regarded as an expression of only a moderate relaxation of the influences normally controlling growth. They are clinically benign. While such tumors closely simulating normal tissues are of occa- sional occurrence, in the majority of tumors the formative powers of the cells from which they develop display certain departures from the normal types of the classes to which they belong, and the structure of the tumor becomes different from that of the tissue in which it arose. This departure from the normal formative activity is usuallv a reversion to a more primitive type of tissue-formation, the control- ling influences normally guiding the cells being weakened to such a degree that the tissues produced fail to acquire the structural differ- TUMORS. 343 entiation of the parent-tissue. This failure in structural differen- tiation may be so great that the resulting tumor resembles embryonic tissue. Such tumors are clinically malignant, and, in general, it may be said that the degree of malignancy is approximately proportional to the lack of specialization exhibited by the formative activities of the cells. Up to this point we have considered two possibilities in the production of tumors: 1. The production of a tumor by cells which no longer respond to the needs of the organism in perform- ing work for the general good, but which remain subject to the influences controlling the structural differentiation of the parent- tissue. 2. The formation of a tumor by cells which are less re- strained by normal influences and which exercise their formative powers without conforming to the special differentiation exhibited in the parent-tissue. This we may regard as a reversion of the cells to a less specialized state, in which they exercise their forma- tive powers in elaborating tissues corresponding to those normally present at some earlier stage in the development of the individual. There is a third possibility. The reversion just described may be conceived as affecting the cells involved in tumor-production, but those cells, instead of forming a tissue corresponding to the degree of reversion they have suffered, may become specialized along some divergent line of development and produce a tissue more or less akin to that of the parent-tissue. Thus a tumor composed of bone may be produced within some other form of connective tissue, such as cartilage or fibrous tissue. The dissimilarity between the tis- sues of a tumor and those of the part in which it grows would seem, from this point of view, to depend upon the degree of reversion that had taken place. Even after a tumor has once been formed, portions of it may acquire a different structure, due to reversion on the part of some of its cells or a modification of their formative activities. There appears to be a limit to the extent of these rever- sions. It is found in the early differentiation of the three embry- onic layers. Cells derived from the mesoderm, for example, do not seem to revert to such an undifferentiated condition that they can develop tissues like those normally springing from the epiderm or hvpoderm. A still further complexity of structure may arise from the formative tendencies of different cells within the same growth developing along different lines of specialization. This occasions the production of "mixed" tumors, composed of various tissues 344 HISTOLOGY OF THE MORBID PROCESSES. arranged in a manner usually quite unlike that of any normal organ. In consequence of the numerous variations in tissue-production which may participate in their development it follows that tumors have a marked individuality, and that only certain types of more frequent occurrence can be described. Departures from those types will be met with in practice, and they must each be interpreted in accordance with the insight which the observer can gain as to their nature and tendencies. The more atypical the structure of a growth — i. c, the more it departs from the structure of normal adult tissue — the less likely is it to prove benign ; the more highly cellular it is, the more likely it is either to grow rapidly or to act injuriously upon the whole organism : for its cells derive their nourishment from the general system and throw upon it the task of eliminating their waste- products. Tumors are subject to morbid changes comparable with those affecting normal tissues. They may be the seat of inflamma- tion, infiltrations, and degenerations. In fact, the more cellular forms are exceedingly prone to degenerative changes, due probably to a relative insufficiency of nourishment consequent upon their rapid growth and active metabolism. It is quite likely that the products of those degenerations, when absorbed into the system, act injuriously upon the general health. The effects upon the nutrition of the body occasioned bv the presence of a tumor constitute that part of the clinical picture which is known as " cachexia," and is most marked when the tumor is malignant But cachexia is not necessarily a sign of malignancv, and is not always present, even when the patient has a verv malig- nant form of tumor. The degree of malignancy is measured by the rapidity of growth, the tendency to infiltrate surrounding tissues, and the liability to metastasis, and these depend upon the reproductive activity of the cells and the extent to which their formative activity is displayed in the elaboration of firm intercellular substances. Metastasis takes place when cells become detached from a tumor and are conveyed to some other part of the body, where they find conditions favorable for their continued multiplication. They then produce secondary tumors, which usually closely resemble the pri- mary growth to which they owe their parent-cells. It is evident that a microscopical study of a tumor may be made the basis of pretty accurate estimates of its nature and ten- TUMORS. 345 dencies. The general character of the tissue composing it can be determined ; an approximate idea of the reproductive activity of the cells formed ; the tendency to invade or infiltrate the sur- rounding tissues, and therefore the probability of the occurrence of metastases, estimated ; and the presence of degenerative or other changes observed. The knowledge so gained will throw light upon the clinical significance of the tumor. It is evident, however, that all the knowledge required cannot, in every case, be learned from the examination of a single piece of the tumor. Some of the neces- sary facts are best observed at the periphery of the growth, others in the central portions, and in mixed tumors the various parts of the growth may possess quite different characters. Every tumor must be made the object of a special study, if all the information it is capable of yielding is to be acquired. Before passing to a description of the more common types of tumors we must turn our attention for a moment to their classifica- tion and nomenclature. Tumors are sometimes grouped in two great divisions: 1, the " malignant tumors," which threaten life because of the rapidity of their growth, their infiltration of surrounding structures, and their liability to metastasis ; and, 2, "benign tumors," which are essentially harmless unless they develop in a situation where they interfere with the function of some vital organ, or unless they appropriate so much of the nutritive material of the body that the general health suffers. This classification is a purely clinical one, and deserves mention only because of its medical importance. There are many degrees of malignancy, and these can be estimated in individual cases only with the aid of deductions from the structural peculiaritiss of the particular growths. A classification based upon the structure of tumors is, therefore, of greater value than one based merely upon their clinical aspects, for it includes that and much more besides. If we bear in mind the fact that any form of cell capable of multiplying may give rise to a tumor, it will become evident that those tumors composed of a single variety of tissue may be classified in a manner similar to that in which the normal tissues are classified. Such tumors are grouped under the term "histioid," to distinguish them from tumors of more complex struct- ure not analogous to simple elementary tissues, which are collec- tively referred to as "organoid." The histioid tumors are desig- nated by names formed from the word indicating the normal :]4G HISTOLOGY OF THE MORBID PROCESSES. tissue they most closely resemble and the suffix " oma." Thus, a fibroma is a tumor consisting essentially of fibrous tissue — i. e., connective-tissue cells with a fibrous intercellular substance — even if the arrangement of the tissue-elements is not quite like that of normal fibrous tissue. A myoma is a tumor composed of mus- cular tissue, with only so much admixture of fibrous tissue as would be comparable with that found in masses of normal muscle. But as there are smooth and striated muscular tissues, so there are leiomyomata and rhabdomyomata. When a tumor contains two varieties of elementary tissue in such proportions that neither can be considered as subsidiary to the other, it receives a compound name, in which the most prominent or important constituent tis- sue is placed last, being qualified by the name of the less impor- tant tissue. Thus there are myofibromata, in which the fibrous tissue is more prominent than the muscular tissue ; and fibromyomata, in which the muscular tissue predominates. In like manner three or more tissues may be designated as forming a tumor by such names as osteochondrofibroma, myxoehondrofibroma, etc., implying that the growths are composed of fibrous tissue with an admixture of cartilage and bone, or cartilage and mucous tissue, etc. The problem of classification is not so simple when we take up the consideration of tumors less closely resembling the normal tissues that are found in the adult body. Those tumors which are akin to embryonic tissues still retain names that have come down from earlier times, and which were conferred on them because of some characteristic visible to the unaided eye. Those of con- nective-tissue origin are called sarcomata (singular, sarcoma), which means tumors of fleshy nature ; and those containing tissues derived from epithelium are called carcinomata, or cancers, because by virtue of their infiltration of the surrounding tissues they possess a fanciful resemblance to a crab. The terms sarcoma and carcinoma have, in the course of time, become more defined, and are now re- stricted to certain well-marked types of structure. The carcinomata are composed of fibrous tissue and epithelium, the one derived orig- inally from the mesoderm, the other from either the epiderm or hypo- derm. In this dual origin they resemble the viscera of the body, and may, therefore, be regarded as among the simpler members of the group of organoid tumors. The most complex members of that group are the " teratomata," which contain structures simulating hair, teeth, bones, etc., arranged without definite order, and often TUMORS. 347 present in great numbers. They spring from the reproductive organs of the body, and appear to be erratic attempts at the pro- duction of new individuals. A new formation of bloodvessels accompanies the development of tumors, and these vessels are associated with a supporting con- nective tissue which may be conceived as a part of this addition to the vascular system of the body, rather than as an integral part of the tumor itself. This development of new bloodvessels is analogous to that which takes place in the course of some of the inflammatory processes, and appears to be brought about in the same manner. I. THE CONNECTIVE-TISSUE TUMORS. 1. Fibroma. — The structure of a fibroma is apt to resemble that of the particular fibrous tissue in which it develops. Very soft varieties frequently spring from the submucous tissues of the nose, pharynx, Fig. 308. Section of a nodular fibroma. (Birch-Hirschfeld.) The dense fibrous tissue is in irregular nodules, between which are bands of less dense fibrous tissue containing blood- vessels. and rectum, forming polypoid growths projecting from the surface of the mucous membrane. They are composed of delicate bands of fibres, loosely disposed to form an open meshwork, which is filled 348 HISTOLOGY OF THE MORBID PROCESSES. with a fluid resembling serum. In the fluid occasional fibres of still more delicate structure may be seen, together with lymphoid cells, either isolated or in little groups like imperfectly formed lymph-follicles. The surface of the growth is formed by a layer of rather denser fibrous tissue, which is covered by a continuation of the epithelium belonging to the mucous membrane. Similar soft fibromata sometimes take origin from the subcutaneous tissues, but fibromata of the skin are usually of denser structure, the bands of fibrous tissue being coarser, more compact, and less loosely arranged. (Edema may make these tumors look very much like the first variety. Harder varieties of fibroma take origin from such dense forms of fibrous tissue as compose the dura mater, the fascise, periosteum, Fig. 309. Dense form of fibroma. (Ribbert.) Section from a fibroma of the dura mater. The inter- cellular substance is very compact and the cells compressed. The latter are most numerous in the neighborhood of the narrow vessel, a, which, together with a branch, is cut longitudinally. Fig. 310. ','";*• •■ 'V^O-'-k "■' ■- Dense form of fibroma. (Eibbert.) Section from older portion of a keloid. Dense masses of compact, apparently homogeneous intercellular substance interlace to form the chief bulk of the tissue. The cells are so few in number and so compressed that they are hardly distinguishable, and haye been omitted from the figure. etc., and those fibromata that occur in the uterus are of similar character. They are usually composed of nodular masses of dense TUMORS. 349 structure, which are held together by a more areolar fibrous tissue supporting the larger bloodvessels of the tumor (Fig. 308). Among the hardest of the fibrous new-formations is the keloid, which in its oldest parts resembles old cicatricial tissue, the fibrous inter- cellular substance being compacted into dense, almost homogeneous masses and bands, in which the nuclei of the cells are barely dis- cernible (Figs. 309 and 310). Fibromata do not always have a nodular character, even when they are of dense structure. They sometimes occur in a diffuse Fig. 311. Intralobular fibroma of the breast. (Ziegler.) a, acini and ducts of the gland ; b, new- formed fibrous tissue; c, areolar tissue of the interstitium, containing the vascular supply. form, surrounding and enclosing the structures of the organ in which they develop. Such diffuse fibromata of the mammary gland are not uncommon, and two varieties may be distinguished : 1, those in which the fibrous tissue develops between the lobules of the gland, separating them from each other by broad bands of dense character, the interlobular form ; and, 2, the intralobular form, in which the individual acini of the gland are separated and sur- rounded by bands of fibrous tissue (Fig. 31 1). These diffuse fibroin- 350 HISTOLOGY OF THE MORBID PROCESSES. ata of the breast must not be mistaken for carcinomata, which they superficially resemble when the glandular epithelium has undergone atrophy due to pressure. In general appearance under the microscope these fibromata resemble the outcome of a chronic interstitial inflammation, but they do not seem to owe their origin to an inflammatory process. Fibromata may undergo localized softening, due to fatty meta- morphosis and necrosis. More frequently they are the seat of cal- cification, the lime-salts being deposited in granules within the intercellular substance, or in little globular masses, variously aggre- gated. These calcified portions are apt to acquire a diffuse blue color in sections that have been stained with hsemotoxvlin. Mixed tumors, containing fibrous tissue and some other variety of connective tissue, or smooth muscular tissue, are common. Fibrosarcomata and fibromyxomata are liable to metastasis ; the other mixed tumors and pure fibromata are among the most benign of the tumors. 2. Lipoma. — Tumors composed of adipose tissue arise from pre- existent fat, or from fibrous tissue of the areolar variety. Their structure very closely simulates and is frequently indistinguishable from that of normal fat (Fig. 312). But they reveal their inde- pendence of the general economy by not being reduced in size during emaciation of the individual. They sometimes enter into the composition of mixed tumors, such as lipomyxomata, lipofibrom- ata, and fibrolipomata. They often grow to considerable size, may be multiple, but are not liable to metastasis and are benign. Calcification, necrosis, and gangrene may occur in lipomata, but are usually confined to those of large size. 3. Chondroma. — The cartilage entering into the formation of chondromata is usually of the hyaline variety, but sometimes fibro- cartilages are also present, and may, in rare instances entirely replace the hyaline form. The structure of the cartilages differs somewhat from that of the normal types. The cells are less uniform in character and in size, are more irregularly distributed through the matrix, and arc frequently embedded in the latter without an intervening capsule. The tumor is rarely composed exclusively of cartilage, but is usually nodular, the cartilaginous masses being sur- rounded by a fibrous tissue in which the vascular supply of the growth is situated. Chondromata generally arise from p re-existent cartilage, bone, or TUMORS. 351 Fig. 312. Lipoma of the kidney. (Bireh-Hirschfeld.) The boundary between the adipose tissue of the tumor and the renal tissue is not sharply denned. The former occupies the middle of the section and extends to its lower edge. fibrous tissue. When they apparently spring from bone their true origin may be from small remnants of cartilage which have escaped the normal ossification. Fig. 313. Chondrosarcoma of the rib. (Hansemann.) The lower portion of the section is exclusively sarcomatous. The upper part contains cartilaginous tissue, but there are a few spindle- shaped cells in the matrix similar to those in the sarcomatous portion of the growth. Cartilage is a not infrequent constituent of mixed tumors, espe- cially of the parotid gland or testis, when it is usually associated 35'-! HISTOLOGY OF THE MORBID PROCESSES. with mucous and fibrous tissue, adenomatous new formations, or sarcoma (Fig. 313). Chondromata are subject to a number of secondary changes, the most important of which are : calcification ; conversion into a spe- cies of mucoid tissue through softening of the matrix and modi- fication of the cells, which assume a stellate form ; transformation into an osteoid tissue, resembling bone devoid of earthy salts ; or into a fairly well-developed calcified bone (Fig. 314). Local soften- Fig. 314. tWi !&nr$K i4 ; ^-'vA>* 'SsGisSi .'■w-o'- •'- :■-:, -,/' ■7^r> Osteoid endochondroma. Section from a metatastic nodule in the lung. The cartilage is atypical, and is arranged in a manner simulating that of cancellated bone. Between the bands and lamina of cartilage is a mixture of mucous and sarcomatous tissue, myxosar- coma, which has rendered the tumor subject to metastasis. The whole tumor may, then, be called a chondromyxosarcoma. ing of the tumor may also take place through a liquefaction of the matrix and disintegration of the cells. The latter may also undergo a fatty degeneration in parts of a tumor which show no signs of softening of the matrix. Chondromata are classed with the benign tumors, but occasional instances of metastasis are on record. It is difficult to understand how this could take place in the case of the harder chondromata, in which the cartilage is surrounded by a somewhat dense fibrous tissue resembling the normal perichondrium. Where there is an admixt- ure with either sarcomatous or myxomatous tissues, these confer a malignant character upon the mixed tumor, and it is quite possi- TUMORS. 353 ble for fragments of cartilage to become detached from the primary growth and appear in the secondary tumors, should metastasis occur. 4. Osteoma. — The most important tumors containing bone are mixed tumors that are significant chiefly because of their other constituents. Small growths consisting of bone alone, either in its compact or its spongy form, occur in the lung, walls of the air- passages, and, rarely, in other situations (Fig. 315). Where bony Fig. 315. Developing osteoma of the arachnoid. (Zanda.) A, dura mater ; B, as yet non-calcified osteoid tissue ; G, bloodvessel. new formations spring from pre-existent bone — e. g., from parts of the skeleton — they are usually the result of" some inflammatory proc- ess, and are not to be grouped among the tumors. In mixed tumors bone is frequently associated with fibrous tissue, myxoma, sarcoma, and chondroma. The structure of the bone in tumors presents slight departures from the normal type, just as that of cartilage in chondromata is somewhat atypical. The lacuna? are apt to vary in size, shape, and distribution more than in normal bone, and the system of canaliculi is less perfectly developed. 5. Myxoma. — The mucous tissue of myxomata has its normal prototype in the Whartonian jelly of the umbilical cord. In its purest form it consists of stellate or spindle-shaped cells, with long fibrous processes that lie in a clear, soft, gelatinous, intercellular sub- 23 354 HISTOLOGY OF THE MORBID PROCESSES. stance containing mucin in variable quantities (Fig. 316). This tissue is closely allied to the other forms of connective tissues and tumors are rarely composed of mucous tissue alone. There is usually an admixture with fibrous tissue, bone, cartilage, fat, or sarcoma ; form- Fig. 31 6. Section from a subcutaneous myxoma. (Bireh-Hirschfeld.) ing fibromyxoma, osteomyxoma, chondromyxoma, lipomyxoma, or myxosarcoma (Fig. 317). The flat endothelial cells of connective tissue also sometimes proliferate to such an extent as to form an Fig. 317. Myxosarcoma of the femur. To the left of the section the tissue is nearly pure mucous tissue. Toward the right, this tissue gradually merges into a more highly cellular struct- ure, constituting the sarcomatous element in the growth. It is this admixture with sarcoma that gives the tumor a malignant character. appreciable constituent of the tumor, the cells being large, rather rich in protoplasm and frequently multinucleated. When this de- velopment is pronounced the tumor may be designated a myxen- dothelioma, and approaches the myxosarcomata in character. TUMORS. 355 Mucous tissue is best studied in the fresh condition by pressing small bits flat between a cover-glass and slide. The processes of the cells may then be seen in their continuity; while, if sections are prepared after hardening, many of those processes will be cut in such a way that their connections with the cells in the contiguous sections are destroyed, and they appear as fibres lying free in the intercellular substance. Mucous tissue must be carefully distinguished from cedematous fibrous tissue. Such cedematous tissue possesses cells of a spindle or flat shape, like those usually met with in fibrous tissue ; but the usual fibrous intercellular substance has a loosened texture, due to the presence of fluid between the fibres, which gives the tissue a soft, transparent character not unlike that of mucous tissue. It must also be borne in mind that fibrous and adipose tissues are liable to undergo a mucous degeneration in which the cells assume a more stellate form than is usual with those tissues, and the inter- cellular substances lose their fibrous character and become more homogeneous. Such degenerations are distinguished with difficulty from the tissue which originally develops as mucous tissue, but they have nothing in common with tumors. Myxomata usually develop in fibrous tissue, adipose tissue, or the medulla of bone. In association with cartilage they are not un- common in the parotid gland. When pure they are benign, but their association with sarcoma often gives them a malignant char- acter, the degree of malignancy depending upon that of the sar- comatous tissue present. 6. Endothelioma. — The endotheliomata are connective-tissue tumors which owe their origin to a proliferation of the flat endothelial cells that line the serous cavities, line or form the walls of the blood- vessels and lymphatics, and are present in some of the lymph and other spaces of the fibrous tissues. Young cells of this variety do not have the membranous bodies that characterize the fully devel- oped older cells, but closely resemble the cells of epithelium. It follows that in this class of tumors it is not always easy to determine the origin of the cells from a mere inspection of their shapes and sizes. The situation and general structure of the tumor will often decide this point. Epithelial tumors spring from pre-existent epithelium, either in some normal site or in an unusual situation because of some anomaly of development (e. g., in the neck, owing to imperfect obliteration of the branchial clefts). 356 HISTOLOGY OF THE MORBID PROCESSES. Endotheliomata, on the other hand, spring from the connective tis- sues, often at a point remote from any epithelial structures; c. g., the dura mater. When the endothelioma owes its origin to a proliferation of the flat cells lining the 1 ymph-spaees or vessels it has a plexiform struct- ure, the young cells occupying pre-existent interstices in the tissues or following the arrangement of the vessels (Figs. 318 and 319). As the cells grow older they may become flattened, and are then Fig. 318. *iy id '•'-•'.'■!•..— Endothelioma from the floor of the mouth. (Barth.) Older portion of the growth. This has a general alveolar structure, the alveoli being separated by a vascularized areolar tissue, it, n, necrosed groups of endothelial cells; /), ft, similar necrosed masses that have undergone hyaline degeneration. often imbricated, forming little, pearl-like bodies. These may subsequently undergo degenerative changes, such as hyaline degen- eration, which convert them into homogeneous masses or bands. Where this takes place the tumor has received the name, "cylin- droma." Or the degenerated cells may be the seat of calcareous infil- tration. This is the origin of the psammomata or " sand-tumors" of the cerebral membranes (Fig. 320). In other cases the cells may not acquire the membranous character of adult endothelium, but continue to multiply without such specialization. Then the tumor partakes of the sarcomatous nature of the other connective-tissue tumors of highly cellular structure and devoid of any marked 357 i 'V 2\ Endothelioma from the floor of the mouth. (Barth.) Section showing the advance of the growth into the lymph-spaces : a, karyokinetic figure in an endothelial cell. Other less well-preserved figures are seen in other portions of the section. intercellular substance. This is more particularly the case when the endothelial cells in the adventitia of the bloodvessels rnul- Fig. 320. Early stages in the formation of a psammoma. (Ernst.) a, collection of endothelial cells; b, similar group showing imbrication of the cells and beginning hyaline degeneration ; c, hyaline mass containing a slight deposit of infiltrated calcareous matter, appearing as granules. tiply to form the growth. The cells of the growth are then in intimate relation with the walls of the vessels, and the tumor is 358 HISTOLOGY OF THE MORBID PROCESSES. designated as an angiosarcoma or alveolar sarcoma, according as the cells show a grouping around the vessels or form collections occu- pying the meshes between them (Figs. 321, 322, and 323). This brief outline of a complicated group of tumors will serve to show that some members of that group closely simulate epi- theliomata in their structure, though they are quite different in their Fig. 321. Endothelioma of the ulna. (Driessen.) a, a, alveoli lined with endothelial cells and occupied by blood ; b, areolar tissue between the alveoli, containing capillary vessels, c; d, large vessel closely surrounded by proliferated endothelium. The structure of this tumor is difficult of interpretation. It appears most probable that its origin lay in the prolifera- tion of the endothelium of lymphatics, and that the blood in a, a is due to communica- tions established between the bloodvessels and elongated and anastomosing alveoli of the tumor. The cells of this growth contained glycogen (see Fig. 249). origin ; while other members of the group are essentially sarcomata, owing their origin to a particular variety of connective-tissue cells and having peculiarities of structure due to the situations in which those cells normally occur. The significance of the tumor will depend in each case upon its tendency to grow rapidly and to infil- trate the surrounding tissues, and its liability to metastasis. These qualities must be estimated by a consideration of the history of TUMORS. 359 the case and the structure and evidences of proliferation presented by the tumor itself. Fig. 322. i . ... - . ■1 - - ■-- :. - - ^ ' '. .'' <~ Angiosarcoma of bone. (Kaufmann.) The lumina of bloodvessels are seen in longitudinal and in cross-section. They are surrounded by a highly cellular tissue, derived from the proliferation of the endothelium forming the perivascular lymphatics. Such tumors are also called " peritheliomata." 7. Sarcoma. — This term includes a variety of tumors differing in the details of their structure and in their clinical significance, but Endothelioma of the thyroid. (Limaeher.) In this example the endothelial cells of the tumor spring from the endothelium of the capillary bloodvessels. Various stages in the proliferation of that tissue are represented in the section. having in common a general resemblance to imperfectly devel- oped or embryonic connective tissue. Such tissues are not infre- 360 HISTOLOGY OF THE MORBID PROCESSES. quently associated with other neoplasmic tissues of higher differen- tiation, forming mixed tumors ; but in such eases the tissues of higher type are not the result of a progressive development on the part of the sarcomatous tissue, for the essential feature of the latter is that it remains in a primitive condition, the formative powers of its cells being chiefly confined to a reproduction of fresh cells, and not to the elaboration of intercellular substances which would convert the tissue into some variety of adult connective tissue. In this respect, as well as in the absence of any natural limitation of growth, the sarcomata differ from the tissues of somewhat similar structure which result from the rejuv- enescence of connective tissue in the productive stages of inflam- mation leading to repair. Some forms of sarcoma closely resemble granulation-tissue, for both have the same origin from the cells of the connective tissues ; but the two must be sharply distinguished from each other, for their tendencies and usefulness are extremely different. The formation of granulation-tissue has a definite cause, and it undergoes a progressive differentiation into a dense fibrous tissue, which terminates the process (with the possible, but notable, exception of the development of keloid ; which is, however, not sarcoma). Sarcoma, on the other hand, arises without a well- defined cause, shows no tendency to higher differentiation, and continues to grow without any assignable limitations. A further difference that may aid in the decision of whether an undifferen- tiated tissue of connective-tissue type is sarcoma or due to inflam- matory processes lies in the fact that sarcoma has a tendency to infiltrate the surrounding tissues, while the young connective tissue that results from an inflammatory rejuvenescence has not. Sarcomata need not necessarily have the structure of the least differentiated forms of connective tissue. Their cells may show a greater differentiation than is found in that tissue, and there may be a certain amount of intercellular substance of a fibrous or other nature separating the cells. The presence of such a fibrous intercellular substance is an evidence that the forma- tive activity of the cells is not wholly concentrated in the produc- tion of new cells, but is partly diverted to the formation of inter- cellular material. It is therefore a sign of less active growth than would be the case were there no such diversity of activity. The intercellular substances also tend to confine the cells to the growth itself, impeding their penetration into the interstices of the sur- TUMORS. 361 rounding tissues (infiltration) and reducing the probability that some of the cells will be carried to distant parts by the currents of the fluids circulating in the tissues (metastasis). It follows that the presence of intercellular substances having these effects must re- duce the degree of malignancy of the whole growth if they are present throughout its substance. This argument is borne out by the results of experience. The sarcomata might be arranged in a series according to their degrees of malignancy, beginning with those that are most malignant, and have little intercellular substance, and cells which are only slightly, if at all, differentiated, and end- ing with those that can hardly be considered malignant, and which have such an abundant fibrous intercellular substance that their structure closely agrees with that of fibroma. In fact, no sharp line between these sarcomata and the fibromata can be drawn. The two classes of tumor merge into one another : they have the same origin, and differ only in the behavior of their cells in the exercise of their formative activities. Those differences are, however, of the utmost clinical importance. The sarcomata are classified, according to the characters of their component cells, into the round-cell, spindle-cell, giant- cell, melanotic, etc., varieties. They are also subdivided ac- cording to the way in which those cells are arranged. The alveolar sarcomata, for example, consist of groups of cells en- closed in the meshes of a fibrous network. These names are, however, more descriptive than indicative of essentially distinct kinds of tumor, and the demarcation between the different varie- eties is not a sharp one. Many sarcomata consist of cells of various shapes, either in different parts or intermingled throughout the growth. This necessitates the insertion of mixed varieties be- tween the above groups of distinct and relatively pure types. Fur- thermore, the cells not only differ in shape, but also in size, so that a distinction may be made between the small round-cell sarcom- ata and the large round-cell variety ; but notwithstanding the fact that this grouping is somewhat artificial, it has a certain clinical value, because it indicates in a rough way the degree of differ- entiation attained by the tumor, and for this reason it will be well to adhere to this classification and to consider the purer types sepa- rately, bearing in mind that the mixed forms of sarcoma possess characters intermediate between those of the simpler forms upon which the classification is primarily based. 362 HISTOLOGY OF THE MORBID PROCESSES. a. Small Eound-cell Sarcoma. — This variety presents the least degree of structural differentiation. The substance of the tumor is composed of small, round cells with single vesicular nuclei enclosed in very little cytoplasm. They are so closely aggregated that they appear to be in contact; but careful examination will often reveal a small amount of a nearly homogeneous, finely granular, or slightly fibrillated intercellular substance (Figs. 324 and 325). The tumor is supplied with blood- vessels having very thin walls, Fig. 325. Fig. 324. Small round-cell sarcoma of the neck. Fig. 324.— Section only moderately magnified, showing the extremely cellular character of the growth ; the great friability of the tissue is owing to the minimal amount of inter- cellular substance it contains and the intimate relations between the tissue of the tumor and the walls of relatively large, thin-walled bloodvessels. Pig. 325.— Sketch of a fragment of the tumor, more highly magnified. The cytoplasm around the nuclei is hardly distinguishable, and the cells are separated by only a small amount of an indefinite intercellular substance. formed of a single layer of cells, which are usually more protoplasmic than those of fully developed endothelium. These vessels may be very abundant, but, especially if the tumor has been removed by operation, they are likely to be empty and their walls so collapsed that they are not easy of recognition. When seen in longitudinal sec- tion these emptied vessels appear as a double line of elongated, some- what fusiform cells, lying in close contact with the cells of the rest of the tumor. In cross-section they are still more difficult of detec- tion, since the swollen endothelial cells then look very much like the contiguous cells of the growth itself. Where the sarcoma is infiltrating the surrounding tissues groups of the round cells, distinguished from the leucocytes which may be present by the character of their nuclei, appear in the interstices of the tissue, the formed elements of which undergo atrophy, either because subjected to increased pressure or because their nutrition is interfered with (Fig. 326). In this way the tumor increases the TUMORS. 363 territory which it occupies, but the more central portions also grow. After a certain stage of growth has been attained the older portions of the tumor are liable to undergo degenerations or necrosis. It is evident, from the structure of this variety of sarcoma, that it must be very prone to suffer metastasis. This may take place through the lymphatics of the surrounding tissues, favored by the infiltrating qualities of the growth ; or it may take place through the bloodvessels, some of the cells finding their way through the thin walls of the vessels in the tumor itself, or into the lumina of larger vessels through an infiltration of their walls. In either Fig. 326. Small round-cell sarcoma of the pelvis, infiltrating dense fibrous tissue. of these ways a generalization of the growth may take place, sec- ondary nodules appearing in many parts of the body. Round-cell sarcomata of this type are liable to arise in the connective fibrous tissue between the muscles, in the fasciae, etc. They also find their origin in the skin, testis, and ovary. They are among the most malignant of the sarcomata, growing rapidly, infiltrating their surroundings, and undergoing metastasis. b. Lymphosarcoma. — This variety of sarcoma differs only slightly in structure from the small round-cell form in possessing a somewhat more elaborate stroma, a term which could hardly be applied to the small amount of intercellular substance found in the latter. In the lymphosarcomata the cells closely resemble those of the small round-cell variety of sarcoma, but they lie loosely aggregated in the meshes of a reticulum of fibres, many of which constitute the processes of stellate cells penetrating the substance of the growth 364 HISTOLOGY OF THE MORBID PROCESSES. and possibly joining each other This reticulum is somewhat more pronounced around the bloodvessels which it supports. The cells may be shaken out of this reticulum, if unembedded sections are agi- tated with water (Fig. 327). Fig. 327. 2& #, W-'i Mi 4#&:m,M, r ill , J), , ii Sections from lymphosarcomata. (Kaufmann.) I, firmer variety, with a pronounced stroma; from a mediastinal tumor. II, softer variety, with a more delicate stroma; from a tumor of the small intestine, a, capillary bloodvessel. This structure closely resembles that of the lymphadenoid tissue found in the normal lymph-nodes, and there is danger of con- founding the growth with a simple or inflammatory hyperplasia of those organs. This danger is enhanced by the fact that these sar- comata frequently find their origin in a lymph-gland or the lymph- adenoid tissue in the mucous membranes. AVhen the enlargement of the gland is the result of hyperplasia the superabundant tissue is confined within the capsule of the gland, which enlarges as its contents increase in amount. There is also a history of some inflammatory process within the lymphatic province to which the gland belongs. Such is not the case when the increase of tissue is due to the development of a tumor. The growth usually pierces the capsule of the gland, and cannot be traced to inflammatory causes. This penetration of the capsule is an evidence of the in- filtrating power of the growth. Like the small round-cell sar- coma, this variety is liable to early and extensive metastases, and is hardly less malignant than that form. <•. Large Round-cell Sarcoma. — As the title implies, this tumor is composed of larger cells than those found in the small round-cell sarcomata. The greater size is due to a larger amount of cytoplasm, in which are rather large round or oval vesicular nuclei, usually one in each cell, but not infrequently cells with two TUMORS. 365 or even more nuclei are observed. The intercellular substance is more abundant and more distinctly fibrillated than is the ease in the small round-cell sarcomata, but it is not uniformly distributed between the individual cells. These are usually aggregated in groups, which are surrounded by the denser bands of fibrous tissue. From these, little fibrous twigs may sometimes be seen penetrating between the individual cells of the group. This arrangement gives sections of the growth au alveolar appearance (Fig. 328). The Fig. 328. Large round-cell sarcoma of the tongue : », large round cell containing three nuclei ; b, delicate fibrous stroma supporting the cells of the growth. At the point 6 this stroma contains a collapsed capillary bloodvessel. The large round cells are probably of endo- thelial origin. The growth occurred in a man aged sixty-one years, and in the course of eight months had attained the size of a hickory-nut. fibrous tissue itself may be highly developed, resembling the adult form ; or it may be more highly cellular and contain large spindle- shaped cells. AVhen this is the ease the tumor becomes a mixed- cell sarcoma composed of large cells, partly round, partly fusiform. The large round-cell sarcomata spring from the same tissues that give rise to the small round-cell sarcomata, but it is probable that they owe their production in large measure to a proliferation of the endothelial cells of those tissues, and are, therefore, etiologi- callv related to the endotheliomata. They grow less rapidly than the small round-cell and lympho-sarcomata, and, as would be ex- pected from a study of their structure, they are less prone to infiltrate their surroundings or to be subject to metastasis. They are, to a corresponding degree, less malignant in their clinical mani- festations. d. Spixdle-cell Sarcomata. — The shape of the cells of this group of tumors betokens a higher state of differentiation than is found in the small round-cell sarcomata, the cells having more 366 HISTOLOGY OF THE MORBID PROCESSES. nearly approached the character of those found in the adult fibrous tissues ; but although in this respect all the tumors of this group are more nearly like the normal tissues, they differ greatly among themselves in regard to the extent to which the formative activities of their cells are displayed in the production of intercellular sub- stances. Some possess hardly more intercellular substance than the small round-cell varieties, while others have the appearance of a rather highly cellular fibrous tissue, the intercellular substances being abundant. The fusiform cells of the tumor possess oval vesicular nuclei, around which is an amount of cytoplasm varying in the different individual growths. Sometimes the cytoplasm is abundant, and the tumor appears composed of large spindle-shaped cells, tapering at their ends to form processes of various lengths (Fig. 329). In Fig. 329. .Large spindle-cell sarcoma. (Birch-Hirschfeld.) other cases the cells are small and the cytoplasm is reduced to a thin investment of the nucleus, at the ends of which it rapidly dwindles to a very thin fibrous process. The spindle-cell sarcomata may, therefore, be divided into large- and small-cell varieties. The cells are usually arranged with their long axes parallel to each other, forming bundles or broad bands of tissue, in which the cells all have the same general position. This direction is generally the same as that taken by the bloodvessels (Fig. 330). These have very thin walls, as in the preceding varieties of sarcoma, and the cells of the tumor appear to be in direct contact with the outside TUMORS. 367 of the vessels. The cellular bundles may not all lie parallel to each other, but frequently are interwoven, so that a given section will contain longitudinal, cross, and oblique sections of the indi- vidual cells. Such appearances must not be mistaken for the some- what similar aspect of sections of mixed-cell sarcomata. The spindle-cell sarcomata are among the most common of tu- mors. They may arise from any of the connective tissues. When they spring from the periosteum they are apt to have an imper- fectly formed bony tissue associated with the structure of the sar- Spindle-cell sarcoma. (Rindfleisch.) Where the cells of the tumor lie parallel to the plane of the section their spindle shape is manifest ; where they are perpendicular to the plane of the section their cross-sections appear round. The bloodvessels appear to have no proper walls, but to he hounded by the tissue of the neoplasm. coma. They then form osteosarcoma^ or osteoid sarcomata, accord- ing to the perfection with which the structure of normal bone is reproduced. In judging of the probable malignancy of a given specimen of spindle-cell sarcoma, the rapidity of its growth, as evidenced by the number of mitotic figures seen in the cells, and the abundance of fibrous intercellular substance, must be taken into consideration. As a group, the spindle-cell sarcomata are less malignant than the small round-cell sarcomata ; but this is because the majority of spindle-cell sarcomata have a well-marked intercellular sub- stance of fibrous character. Those forms which are almost desti- tute of this are hardly less malignant than the small round-cell variety (Figs. 331 and 332). e. Giant-cell Sarcoma. — This form of sarcoma is charac- terized by the presence of large, multinucleated cells lying among the other cells of the growth. These giant-cells may be scattered 368 HISTOLOGY OF THE MORBID PROCESSES. Fig. 331. Example of a highly malignant variety of spindle-cell sarcoma. Sarcoma of the uterus with oval nuclei, indicating somewhat spindle-shaped cells. In other respects the character of the tumor resembles that of a small round-cell sarcoma, a, contiguous fibrous tissue of the uterus; b, sarcomatous tissue ; c, bloodvessels, (v. Kahlden.) Fig. 332. Example of a highly malignant spindle-cell sarcoma. Spindle-cell sarcoma infiltrating the liver. I z, liver-i-clls; s s z, spindle-cells of the sarcoma; c, endothelium of the intra- lobular capillaries. (Heukelom.) TUMORS. 369 pretty uniformly throughout the growth, or they may be much more abundant in some places than in others. The cells with single nuclei, among which the giant-cells are found, may be of the spindle-shaped variety, or they may be polymorphic, in which case cells of various shapes and sizes are met with. The giant-cell sarcomata are usually derived from the medulla of bone. They constitute the most common form of epulis (Fig. 333), and frequently attain very large dimensions when they take Fig. 333. 5 Giant-cell sarcoma of the superior maxilla ; epulis : a, large giant-cell, with numerous nuclei ; b, tangential section of a similar cell. Aside from the giant-cells, the growth is composed of spindle-cells and a moderate amount of a fibrous intercellular substance. The tumor was removed from a man forty-one years of age, and was of slow growth, having attained the size of a filbert in two and a half years. their origin in the marrow of the larger bones, such as the femur or tibia. They are not, however, confined to bone, but may occur in other situations ; e. g., the breast. The malignancy of giant-cell sarcomata must be estimated in individual cases according to the principles already elucidated. /. Melanosaecoma. — Sarcomata which spring from pigmented tissues, such as the choroid of the eye, pigmented moles, etc., fre- quently show a pigmentation of their constituent cells, the pigment appearing as brown granules of various size within the cytoplasm of the cells. The cells are not all equally affected, and many may be seen without any sign of pigmentation. The tumors are apt to be of the spindle-cell or large round-cell varieties, and are 24 370 UISTOLOCY OF THE MORBID PROCESSES. Fig. 334. Melanosarcoma of the sldn. (Eibbert.) The growth is an alveolar large round-cell sarcoma, containing cells that have undergone a pigmentary degeneration. Fume of these cells contain so much pigment that the cellular constituents are invisible. considered as rather more malignant than the non-pigmented forms of those tumors (Fig. 334). II. THE MUSCULAR TUMORS. Muscular fibres of either the smooth involuntary or the striated variety may enter into the formation of tumors. Tumors made up of the former are called leiomyomata; those containing striated muscle, rhabdomyomata. 1. Leiomyoma. — The cells of the tissue forming leiomyomata very closely resemble those of normal smooth muscular tissue, but they may show a greater variation in size. They are arranged in bundles, their long axes parallel to each other; and these bundles are inter- woven in such a way that sections of the tumor contain longitudinal, oblique, and cross-sections of the individual fibres (Fig. 335). Between the bundles there is a variahle amount of fibrous tissue, giving sup- port to the bloodvessels of the tumor. This fibrous tissue may be so abundant as to form a large element in the structure of the tumor, which is then denominated a fibromyoma. It may, also, occasion- ally be imperfectly developed, converting the growth into a leio- myosarcoma. The muscular tissue may undergo a hyaline degen- eration and become the seat of calcareous infiltration, or the cells may be the seat of fatty degeneration with subsequent softening. Leiomyomata arise in parts which normally contain smooth mus- TUMORS. Fig. 335. 371 Leiomyoma of the uterus. (Birch-Hirschfeld.) cular tissue. They are common in the uterus, but may occur in the Fig. 336. Rhabdomyosarcoma of the kidney: a, a, a, imperfectly developed striated muscle-fibres ; b, tissue composed of small round and spindle-shaped cells, separated by considerable deli- cate fibrous intercellular substance. In other parts of the growth, which was the size of the fist, this tissue was more distinctly sarcomatous and the amount of muscular tissue smaller. The child from which this tumor was removed was about two years old. intestinal walls, the urinary tract, or the skin. When pure, or when associated with fibrous tissue alone, they are benign. 372 HISTOLOGY OF THE MORBID PBOCESSES. 2. Rhabdomyoma. — The striated muscle-fibres of rhabdomyomata are often so imperfectly developed that they are difficult of recognition. They are much more attenuated than the normal fibres, and may be reduced to very narrow and tapering structures that possess only traces of striation. Staining with eosin will often aid their detection among Fig. 337. Isolated muscle-fibres from a rhabdomyoma of the oesophagus. (Wolfensberger.) a, b, appearances simulating a sarcolemma, probably due to adherent fragments of the inter- cellular substance. the fibres of the connective tissue surrounding them, as it stains the contractile substance a coppery-red. The nuclei of the muscle-cells are frequently numerous, and may occupy the centre of the fibre, the imperfectly formed contractile substance lying at the periphery. In some rare cases the tumor is composed almost exclusively of TUMORS. 373 striated muscle-fibres, arranged in irregular, interwoven bands, with a little vascular fibrous tissue among them. In other cases the muscular fibres are sparsely distributed through the growth, and can often be found only after a prolonged search. In these cases the tissue in which the muscle is situated is usually some variety of sarcoma, when the whole tumor is known as a rhabdomyosarcoma (Figs. 336, 337, and 338). Such mixed tumors are most frequently found in the genito-urinary tract, especially in the kidney, and may attain very large size. They are apt to occur in the early years of Fig. 338. Isolated cells from a rhabdomyoma of the heart. (Cesaris-Demel.) life, and are probably due to developmental anomalies. The sarcom- atous element, which is usually predominant, gives them a highly malignant character. III. THE ANGIOMATOUS TUMORS. Reference has already been made to the manner in which the bloodvessels of a part may proliferate under the influence of the inflammatory process, and also to the fact that when tumors develop the bloodvessels proliferate in a similar way to form new vascular areas within the tumor, from which the latter derives its nourishment. These instances of proliferation may be regarded as the natural response on the part of the vascular system to the de- mand thrown upon it by the formation of new tissues. In a general way, they are limited to the needs of the tissues which they supply. A vascular proliferation may, however, take place irrespective of 374 HISTOLOGY OF THE MORBID PROCESSES. any such demand, and continue without any such limitation. In this way the vascular tumors, or angiomata, are produced. We may regard them as springing, not from a single tissue or an adven- titious combination of tissues, but from one of those anatomical " systems " in which several tissues are normally associated in a definite arrangement, and, under normal conditions, develop together to form well-defined structures distributed throughout the body. There are three such systems of associated tissues : the bloodvessels, the lymphatic system, and the nervous system. Each of these may enter into the formation of an apparently purposeless neoplasm, forming the hasmangiomata, lymphangiomata, and neuromata. Of these, the first two are of vascular character and mesodermic origin, and their consideration naturally follows that of the other tumors arising in tissues of similar embryonic origin. 1. Hemangioma. — The bloodvessels entering into the formation of hsemangiomata are usually relatively deficient in the develop- ment of their muscular coats. They resemble large capillaries which have been reinforced by a covering of fibrous tissue. The vessels may lie with their walls almost in contact with each other, or there may be a considerable amount of interstitial tissue between them. It is not always possible to decide in a given case whether the vessels are strictly of new formation or not. Masses consisting essentially of bloodvessels may arise through dilatation of pre- existent vessels, with atrophy of the tissues that normally lie be- tween them. This is the origin of the angiomata of the liver, and many of the angiomata of the skin (nffivi) are explicable in the same manner. In the liver the capillaries of the lobules become dilated and their walls thickened, the parenchymatous cells between them disappearing by atrophy, and, as the capillary walls come in contact and exert mutual pressure, they may undergo atrophy, per- mitting a communication between their lumina, so that a spongy mass of tissue results, with large cavities filled with blood (Fig. 339). Such "cavernous angiomata" hardly constitute tumors in the restricted sense in which that term has been used hitherto. They are rather ectatic states of the vessels normally present in the parts where they are found. Somewhat more akin to the true tumors are the masses which arise through elongation and widening of the vessels of a part (aneurisma racemosa), for in this case there is a real reproduction or growth of the vessels. TUMORS. 375 Angiosarcomata are tumors in which a new formation of blood- vessels with a sarcomatous adventitia springs from connective tissue either in the general fibrous structures of the body or the interstitial tissue of the viscera. Sections of these tumors sometimes reveal thin-walled vessels with a distinct, broad zone of sarcomatous tissue around them, resembling an enormously thickened adventitia of embryonic tissue (Fig. 322). In other cases the embryonic tissue that represents the adventitia of the separate vessels is fused into a mass of sarcomatous tissue lying between the vessels. The tumor Fig. 339. Cavernous hemangioma of the liver: a, substance of the liver; b, fibrous capsule formed at the margin of the angioma, probably the result of a chronic productive inflammation ; c, space filled with blood ; d, atrophic wall between two of the spaces of the angioma. is then similar in structure to an ordinary sarcoma, in which the vessels are more abundant, perhaps, than is usual. When the angiomata have been removed by operation the vessels are usually emptied by the pressure that has been exerted upon their tissues by the operative manipulations. This condition often gives rise to puzzling appearances, when the endothelial cells of the vas- cular walls are swollen or richer in cytoplasm than normal adult endothelium. Sections of the tumor then look like sections through a gland. The true nature of the tubules can generally be deter- mined by the appearance of the lumina, which in the collapsed ves- sels is not circular, while in the glands it is nearly so if the section 370 HISTOLOGY OF THE MORBID PROCESSES. be transverse to the direction of the tube. In glandular tubules the epithelial cells are usually well-defined and clearly distinguishable from each other. This is not apt to be the case in immature endo- thelium. 2. Lymphangioma.— What has already been said with respect to the haemangiomata applies to the lymphangiomata. Many of these tumors appear to be the result of a dilatation of the lymphatic vessels normally present in the tissues ; but cases may arise in which there is a real reproduction of those vessels. The spaces in the tumor are either empty and collapsed, or they contain lymph and not blood. The walls of the vessels are frequently thickened by the production of fibrous tissue around them. IV. THE EPITHELIAL TUMORS. The epithelium, which by its proliferation gives rise to tumors, may be situated either within a glandular structure of the body or upon one of its free surfaces, such as the skin or a mucous mem- brane. The tumors which result are not wholly composed of epithe- lium. There is always a development of the connective tissue of the part, furnishing a vascularized nutrient substratum for the epithelium. The epithelium of glandular organs may give rise to two sorts of tumors, the adenomata and the carcinomata. The stratified epithelium of the skin and some of the mucous membranes proliferate to form the epitheliomata. 1. Adenoma. — In this form of epithelial tumor there is a more or less perfect adherence to the structure of a normal gland. AVhen adenomata spring from the epithelium of tubular or acinous glands the lobules of the tumor are composed of tubes or acini with a distinct lining of epithelium enclosing their lumina (Fig. 340). But there is almost always some departure from the typical structure of a gland ; the lobules may be of unequal size in a more marked degree than is usual, the character of the epithelial lining may be abnormal, or the distribution and arrangement of the lobules may betray an abnormal tendency on the part of the growth. The latter feature is exemplified in the adenomata of the rectum, in which the new-formed glandular structure is apt to penetrate the muscularis mucosaj and develop abundantly in the submucous coat or even in the deeper, muscular tissues of that part of the in- testine. TUMORS. 377 The adenomata of the breast deserve a rather close study. A perfectly simple adenoma of this gland appears to be a very rare growth. There is nearly always an association with diffuse fibroma, forming an adenofibroma. These are often cystic, an accumulation of a serous fluid in the acini causing their dilatation (cystic adeno- fibroma) (Fig. 341). In other cases the fibromatous tissue grows Fig. 340. ?m <&{Sfo£j£/2i * : / r ffl ■/&*Jg m4m ., ^i»-! Adenoma of the pancreas. (Cesaris-Demel.) The atypical nature of the growth is revealed by the character of the epithelial cells, their arrangement within the alveoli, and the disposition of the latter with respect to each other and the interstitial tissue. into the acini, which are enlarged to receive these ingrowths from their walls. The ingrowing masses of fibrous tissue are covered with epithelium like that lining the rest of the acinus, a fact which would be expected when we reflect that the ingrowth is a sort of intrusion of the wall of the acinus itself. Sometimes these in- growths have a papillomatous character, but more frequently they have a globular form and give off globular branches within the acinus. Sections of such growths often have a complicated appear- ance. Irregular and branching bands of epithelium are seen cours- ing through a mass of fibrous tissue. They are the epithelial linings of the acini which have b: j en brought into contact by the ingrowths of fibrous tissue, obliterating the lumina of the acini. 378 HISTOLOGY OF THE MORBID PROCESSES. Part of this epithelium is, therefore, that which may be said to line the dilated acini ; the rest, that which covers the fibrous tissue, which has grown into the acini and caused contact of the epithe- lial layers with obliteration of the lumina. Where the pedicles of these ingrowths are small, sections may contain rings of epithe- lium surrounding an isolated mass of fibrous tissue if the section does not include the pedicle of that particular ingrowth (Fig. 342). Fig. 341. Adenofibroma of the breast. (Bireh-Hirschfeld.) The section shows a tendency toward cystic dilatation of the glandular acini. If the tumor is examined macroscopically, the ingrowths may often be lifted from the acini in which they lie. These tumors have received the name " intracanalicular adenofibroma." They must be carefully distinguished from the scirrhous carcinomata of the breast, which, upon superficial examination, they somewhat resemble. In examining sections of the breast with a view to determining TUMORS. Fig. 342. 379 Intracanalicular adenofibroma of the breast. (Kaufmann.) In tbis example the lumina of the acini have not been obliterated, and a correct interpretation of the appearances pre- sents no difficulty. Fig. 343. Section from the mammary gland of a nullipara, aged eighteen ; moderately magnified. (Altmann.) 380 HISTOLOGY OF THE MORBID PROCESSES. the question of the existence of a tumor the normal variations in that organ must be carefully considered. In the description of the normal mammary gland it was stated that the microscopical struct- ure differed greatly according to the functional activity of the Fig. 344. 5 f '^-J"J."/<>«'/^=^-} Section from the mammary gland of a nullipara, aged eighteen; more highly magnified. (Altmann.) organ. It is proper to recur to those differences in this connection because of the importance of many of the mammary tumors, that gland being one of the common sites of carcinoma and adenoma. Fig. 345. Section from the mammary gland of a nullipara, aged twenty-two ; slightly magnified. (Altmann.) In Figs. 343 to 350 sections of the gland in various stages of development and involution are represented. Figs. 343 to 346 represent sections from the breasts of nulliparae, aged respectively eighteen and twenty -two years. The parenchyma of the gland has TUMORS. 381 a general tubular structure, the acini being in an undeveloped state. Figs. 347 and 348 show sections of the mammary gland of a Section from the mammary gland of a nullipara, aged twenty-two ; more highly magnified. (Altmann.) woman, aged thirty-eight, who had born five children. The sec- tions were taken at the beginning of functional activity of the gland. Figs. 349 and 350 represent involuted mammary glands, respec- Fig. 347. Section of the mammary gland at the beginning of lactation; moderately magnified. (Altmann.) tively nine and fourteen months after functional activity had been arrested. Adenomata are usually of benign character ; but, as is the case with all neoplasms, it will not do to conclude that a growth is harm- less merely because it can be included in a group of tumors that are usually benign. The evidence as to its tendencies revealed by the. 382 HISTOLOHY OF THE MORBID PROCESSES. structure of each individual tumor must be carefully weighed before a conclusion an to its benignancy or malignancy is reached. Aden- omata are benign in proportion as they adhere to the structure of a normal gland of the type which they simulate. They approach Fig. 348. Section of the mammary gland at the beginning of lactation; more highly magnified. (Altmann.) malignancy when they become atypical and show a tendency to infiltrate their surroundings. The adenomata of the rectum, already referred to, are likely to prove malignant, and in their structure they show a departure from the simple type of tubular gland normally present in the rectum (Fig. 351). They also dis- Fig. 349. '^■^. ■^*nMB& Section of the mammary gland in a state of involution. (Altmann.) From a woman, aged twenty-five, nine months after the cessation of functional activity. play a marked tendency to infiltrate their surroundings. While they belong to a group of generally benign tumors, they possess an atypical structure and a power of infiltration that reveal their malignant character. 2. Carcinoma. — The epithelium of developing secreting glands TUMORS. 383 first appears as little solid columns of epithelial cells, which spring from the epithelium covering the part and penetrate the underlying Fig. 350. Section of mammary gland in a state of involution. (Altmann.) From a woman, aged thirty-two, fourteen months after functional activity had ceased. tissues (see Fig. 181). These columns subsequently become hollowed to form tubes or sacs lined with secreting epithelium. In carci- Fig. 351. Infiltrating adenoma of the rectum. fHansemann.) The figure represents alveoli of atypical character, differing greatly from the normal glandular structures of that part of the body. The section does not include the infiltrating portion of the growth. nomata the embryonic state of gland-formation is simulated by the growth, so that a carcinoma may be considered as formed upon the 384 HISTOLOGY OF THE MORBID PROCESSES. type of a developing gland in the same sense as a sarcoma is analogous to developing connective tissue. As a result of this structure, sections of carcinomata appear to be composed of alveoli, which are filled with epithelial cells and have walls of fibrous tissue. The character of the epithelium depends chiefly upon the variety from which the tumor sprang. The sizes of the alveoli and the amount of fibrous tissue that sepa- rates them from each other vary in different tumors, and the carci- nomata are divided into rather ill-defined groups, according to the relative abundance of the epithelium they contain as compared with the amount of fibrous tissue They are also subdivided according to the character of the epithelium. «. Medullary carcinomata (Fig. 352) are those in which Medullary carcinoma of the mammary gland. (Hansemann.) The stroma of the tumor is here reduced to a minimal amount of areolar tissue containing the vascular supply of the growth. there is the least amount of fibrous tissue. The alveoli are usually large and filled with polyhedral cells. The fibrous tissue of the alveolar walls may be so reduced in amount as virtuallv to serve merely as a support to the bloodvessels it contains. Such tumors are soft, of rapid growth, and very prone to degenerative changes and metastasis. b. Simple carcinomata contain about an equal amount of epi- thelial and fibrous tissues (Fig. 353). c. Scirrhous carcinomata (Fig. 354) are characterized by small alveoli separated by large quantities of dense fibrous tissue. TUMORS. 385 The latter may so greatly preponderate over the epithelium that there is a possibility of mistaking the tumor for a simple fibroma. Carcinoma simplex mammas. (Kaufmann.) In this growth the stroma is well developed and divides the tumor into a number of intercommunicating alveoli, filled with epithelial cells. Care must be taken not to confound these carcinomata with the intracanalicular adenofibromata already described. In the carcinoma Fig. 354. Scirrhous carcinoma of the breast. (Ribbert.) The bulk of the section Is composed of dense fibrous tissue, in which there are a few rows of epithelial cells, a. there is no ingrowth of fibrous tissue into the alveoli, as in the case of the adenofibroma. The development of the fibrous tissue in 25 386 HISTOLOGY OF THE MORBID PROCESSES. these cancers is probably induced by the proliferation of the epi- thelium, but it sometimes happens that the fibrous tissue form- ing the stroma of the tumor compresses the epithelium after the growth has attained a certain stage of maturity, and causes an atrophy of its cells (atrophying carcinoma). As a result the tumor may suffer a diminution in size, but this shrinkage occurs only in the older parts of the tumor; the peripheral portions continue to It is no indication of a spontaneous cure. Carcinomata are malignant, but differ in the rapidity of their clinical course. Those which are softer — i. e., contain a larger pro- portion of epithelium — are of more rapid growth than the harder varieties ; but they all tend to infiltrate their surroundings and are liable to metastasis. The usual mode of infiltration is for the pro- liferating epithelium to penetrate the lymph-spaces or lymphatic vessels of the neighboring tissues. The cells may advance as solid grow. Fig. 355. Carcinoma invading adipose tissue. The figure represents a section of the fat surrounding the breast in a case of mammary carcinoma. Musses of epithelium are present in the lymphatic spaces of the areolar tissue between the fat-cells. The nuclei of some of the epithelial cells show imperfectly preserved karyokinetic figures. To the right, above, is a group of four epithelial cells surrounded by a round-cell (inflammatory) infiltration. columns pushed out from the growth along these lymph-channels, or cells may become detached from the main growth and be car- ried by the lymph-current for a greater or less distance from the original tumor, to find lodgement in some situation in which the conditions may be favorable for their continued multiplication TUMORS. 387 (Fig. 355). The connective tissue of the new site is then induced to proliferate and form the cancerous stroma. If this transfer of cells is only for a short distance, the process is called infiltration ; if the distance is greater, metastasis. It appears, then, that meta- stasis usually occurs through the lymphatics, as it is through them that the natural extension of the carcinoma takes place. The cells that gain entrance to the lymphatic vessels are most likely to be arrested in the nearest lymph-node, giving rise, if they multiply, Fig. 356. Secondary carcinoma of a lymph-gland. (Ribbert.) Epithelial cells from the primary car- cinoma have been carried by the lymph-current to the node, where they have been arrested in the lymph-sinus. Here they have continued to proliferate, giving origin to a secondary, or metastatic, nodule of carcinoma. to a secondary tumor within it (Fig. 356). These secondary tumors in the lymph-nodes may, after a period of development, furnish cells for a still wider metastasis. Metastasis through the lymphatics is not the only means by which carcinomata may become generalized. They may infiltrate the walls of bloodvessels, usually veins, and finally discharge cells into the blood, giving rise to cancerous embolism with a gen- eral diffusion of secondary nodules in the first capillary district through which the blood is distributed. In this way multiple carcinomata of the liver or lung are produced. The secondary carcinomatous nodules usually resemble the primary tumor, espe- cially as regards the character of the epithelium ; but the relative amount of stroma is very frequently considerably less. A scirrhous carcinoma may give rise to secondary nodules of medullary car- cinoma. The distinction between the different varieties is, therefore, more descriptive than essential. Carcinoma is apt to occasion the development of a cachexia in the patient. The reason for this is probably to be sought in the 388 HISTOLOGY OF THE MORBID PROCESSES. absorption of the products of metabolism from the tumor, rather than in the abstraction of nourishment from the organism. Epi- thelium, especially of the glandular form, is a tissue of great chemical activity, and in carcinomata there is no special outlet for the products of that activity, such as is furnished by the ducts of normal glands. It may, therefore, be reasonable to infer that the products resulting from the chemical activities of the. epithelial cells must be absorbed into the system, and that they may injuriously affect the nutrition and the functions of distant organs. Carcin- omata are also liable to undergo degenerations, the products of which may be deleterious to the organism. A form of carcinoma which differs somewhat in appearance from those that have been mentioned, though it is of essentially the same nature, is the " colloid carcinoma " (Fig. 357). This variety springs Fig. 357 Colloid carcinoma. (Eibbert.) The section represents a delicate stroma of areolar tissue separating alveoli, which are not rilled with cells, but contain the products of their mucous degeneration and a few cells which have not yet undergone complete destruc- tion. from epithelium that under normal conditions secretes mucus. This function renders the cells of the cancer particularly liable to mucoid degeneration, and this may be so extensive as to destrov all or nearly all of the cells in some of the alveoli of the tumor, con- verting them into a soft mucous mass that usually does not appear quite uniform under the microscope. The epithelial cells are gen- erally of columnar form, arranged, at the periphery of the alveoli, with their ends in contact with the alveolar wall. This arrange- TUMORS. Fir. 358. 389 ;Jm Wmtr ■f% Adenocarcinoma of the liver, (v. Heukelon.) a, normal liver-cell: b, mortified epithelial cell entering into the formation of the neoplasm; c, normal nucleus ; (I, nucleus abnor- mally rich in chromatin preparatory to cell-division ; e, fat-globule in the epithelium of the tumor, showing a tendency to fatty degeneration. 390 HISTOLOGY OF THE MORBID PROCESSES. ment of the cells is often strikingly shown in secondary tumors of the lung, in which the cells have appropriated the pulmonary alveoli for their stroma. It occasionally happens that the connective tissue that forms the stroma of a carcinoma does not progress in its development to the formation of fibrous tissue, but assumes a sarcomatous character. Such tumors are called " carcinoma sarcomatosum." A more fre- quent association is one of carcinoma with adenoma, "adenocar- cinoma" (Fig. 358). In these neoplasms, either the two forms of Fig. 359. Epithelioma of the cheek. (Ernst.) a, delicate tongues of epithelium extending into the lymphatics of the part ; b, c, larger masses of epithelium containing pearl-bodies. epithelial tumor may occupy different portions of the growth, or the general character of the growth may be that of a rather typical carcinoma.—/, e., a carcinoma showing indications of a development beyond the undifferentiated state analogous to an embryonic gland — or that of a rather atypical adenoma. TUMORS. 391 3. Epithelioma. — This tumor is essentially a carcinoma springing from stratified epithelium. Under normal circumstances the cells of this variety of epithelium multiply in its deeper layers and are gradually pushed toward the surface while they mature. Epithe- liomata are produced when the proliferating cells penetrate the underlying tissues in columns, which ramify through those tissues and ultimately appear as the contents of well-defined alveoli sur- rounded by a fibrous-tissue stroma similar to that present in car- cinomata (Fig. 359). The epithelium retains its general characters : the cells at the periphery of the alveoli multiply, and either further Fig. 360. Epithelial pearl-body from an epithelioma of the lip : a, pearl-body ; b, surrounding epithe- lium, forming one of the epitheliomatous tongues or columns; e, round-cell infiltra- tion of the contiguous fibrous tissue. infiltrate the surrounding tissues or crowd each other toward the centres of the alveoli as they increase in number and size. Here they eventually undergo keratoid transformation, just as they would upon the surface of the normal epithelium ; only here they are crowded toward the centres of the alveoli, where the horny scales become imbricated to form globular masses, called epithelial " pearl- bodies" (Fig. 360). The epitheliomata may penetrate into the lymphatics and be subject to metastasis in a manner entirely com- parable to that already described above. They are, therefore, malignant, though of slower growth than the medullary or simple carcinomata, at least during the early stages of their development. It should always be borne in mind, when considering the prog- 392 HISTOLOGY OF THE MORBID PROCESSES. nosis in a case of carcinoma or epithelioma, that metastasis may take place while the primary growth is still of very small size, even before attention has been called to the existence of a tumor. An examination of the peripheral portion of the growth will often throw considerable light upon the probability that this has occurred, by revealing an extension of epithelial cells into the lymphatics of the surrounding tissues. Cases of speedy recurrence of such a growth after operation are really cases in which tissues that have thus been infiltrated have not been completely removed. Much has been written within late years advocating the theory of a parasitic causation of carcinomata and epitheliomata. The appearances which have led to this belief are probably due to degenerative or morbid processes within the epithelial cells of the tumor, and not to the presence of parasites ; but further study of this subject may show that parasites have the power of causing rejuvenescence of cells and an emancipation from the ordinary restraints that regulate their development. 4. Cystoma. — Attention has been called to the cystic adenomata of the mamma. Similar cysts may occur in other regions through dilatation of cavities normally present in the tissues by some fluid, usually of a serous character. It is best to exclude evstic growths in which the cystic character is evidently a secondary feature of the tumor, or where a cyst arises from the retention of a secretion or is due to the accumulation of a fluid in a normal cavity, from the group of tumors that are essentially cystic. Thus, for example, simple hydrops folliculorum of the ovary should not be classed with the cystic tumors of that organ. The ovary is the favorite site for cystic tumors of new formation, which may contain only a single cavity (unilocular) or several cav- ities (multilocular). Histologically, they may be grouped in three divisions : 1, simple, in which the walls of the cyst are smooth and covered with epithelium ; 2, papillary, in which there are ingrowths from the walls of the cysts into their cavities, either simple or branch- ing (Fig. 361) ; and, 3, dermoid, which contain structures simulating the normal skin : hair, imperfectly developed teeth, or other highly differentiated tissues, such as bone, etc. In the first two forms the fluid in the cystic cavities may be serous, mucoid, or colloid ; fre- quently it is different in the various cavities of the tumor. In der- moid cysts there is often a greasy substance, similar to the sebum of the skin, derived from sebaceous glands in the cutaneous struct- TUMORS. Fig. 361. 393 ;^'i^-V£->?^*-' : * '-;: >'-''** >%v^ _.«*v *&*, Section from a papillary cystoma of the ovary. (Birch-Hirschfeld.) Part of the wall sepa- rating two cystic cavities is represented. From this wall, papillary ingrowths arise, which project into the cavity of the cyst. They are composed of a delicate areolar tissue covered with columnar epithelium similar to that lining the cysts. ures of the growth. Similar dermoid cysts occasionally develop from the skin, but are usually lined with merely an epidermis, the Gilomata of the brain. (Stroebe.) Composed of glia-cells of small type, with fine processes. 394 HISTOLOGY OF THE MORBID PROCESSES. scales from which accumulate in the cavity of the tumor, where they may be mixed with sebum (wens). 5. Glioma. — The neuroglia, originally of epithelial origin from Fig. 363. Gliomata of the brain. (Stroebe.) Mixed type, containing cells like those in Fig. 362, but also large branching cells simulating ganglion-cells, "glioma gangliocellulare." In sections of gliomata stained by the methods in more general use the delicate processes are often not visible, but the nuclei are prominent. The tumor, therefore, appears highly cellular with a finely granular material (the unstained processes) between the cells. the ectoderm, may proliferate to form tumors, called gliomata. These differ in their structure according to the variations in type presented by the glia-cells composing them (Figs. 362 and 363). V. PAPILLOMATA. Before leaving the subject of tumors it will be necessary to devote a few words to the consideration of growths that cannot be considered as primarily arising from cither epithelium or connective tissues. The papillomata are examples of such growths. These are over-developments of papillary structures normally present, or spring from mucous surfaces where such structures are normally either not present or are but poorly developed. TUMORS. 395 A papilloma consists of vascularized fibrous or areolar tissue springing from a surface which is covered with epithelium. The denser forms which occur — c. g., upon the skin — constitute " warts" ; but much more delicate papillomata may spring from mucous mem- branes, such as that of the bladder, and are then known as villous tumors or villous papillomata. In many cases the denser forms of papilloma appear to be hypertrophies due to irritation. But papil- lomata which seem to be true neoplasms or tumors in the restricted sense of that term hitherto employed appear to be among the possi- bilities of morbid development. PART III. HISTOLOGICAL TECHNIQUE. CHAPTER XXVI. PRACTICAL SUGGESTIONS FOR THE CARE AND USE OF THE MICROSCOPE.— MICROSCOPICAL TECHNIQUE. Ik selecting a microscope the following considerations are of importance : The stand should be supported on three points and rest firmly on the table ; have a rack-and-pinion coarse adjustment, and a fine adjustment free from all loss of motion. It is rarely used in an inclined position, and a jointed stand is unnecessary. A triple nose-piece, or revolver, is a great convenience, and an Abbe con- denser with iris-diaphragm is almost indispensable. Three objectives are needed : a Leitz No. 3 or No. 4, No. 7, and Y^th or j\th oil immersion, or their equivalents of other manu- facture, are suitable powers for general use. Two oculars, No. 2 and No. 4, will answer. The microscope should be protected from direct sunlight and acid fumes, and be kept in a dry, moderately cool place. When not in use it should be covered or placed in its case, to protect it from dust. If the lenses become dirty, they may be wiped with a soft, clean cloth or Japanese paper, either dry or moistened with water, and followed by a dry cloth or paper. Balsam or cedar oil may be removed with a cloth or soft paper moistened with xylol, after which the parts should be carefully wiped dry. In making microchemical tests special care should be taken not to let the reagents come in contact with the objectives. Objects should always be examined in a liquid, unless there is some special reason for examining them in a dry state ; and should be covered with a cover-glass, unless a cursory inspection with a very low power is all that is required. 397 398 HISTOLOGICAL TECHNIQUE. In studying a specimen always use the lowest power that will reveal the structures it is desired to see ; and, in any event, use a low power first, to get a general idea of the topography of the specimen. In this way the portions for more minute study can be readily selected, with a great saving of time. The proper illumination of the specimen is just as important as careful focussing. If the Abbe condenser is in use, employ the plane surface of the mirror during the day ; either the plane or the concave surface when artificial light is used, selecting the surface which causes less glare. The iris-diaphragm should be kept ad- justed so as to give the best definition of the specimen under exam- ination when the latter is in focus. It will be found that when colorless objects are examined a small opening gives the clearest picture, while with colored objects a larger opening is preferable. A small diaphragm serves to bring out the "structure-picture" ; a large diaphragm, the " color-picture " (see p. 402). A bottle of oil of cedar-wood, having approximately the same refractive index as the glass from which the cover-glasses are made, is furnished with the immersion-objectives. When these are used a drop of this oil is placed on the cover, and the end of the objec- tive immersed in this drop. This arrangement permits the light to pass from the object to the bottom lens of the objective without sen- sible refraction, increasing the amount of light entering the objec- tive, the sharpness of definition, and the purity of the color-picture. When the lens has been used the oil should be removed with a soft cloth or Japanese paper. The oil on the cover may be wiped off at once, or it may be allowed to dry and then removed with a cloth moistened with xylol. Microscopical Measurements. — These may be made, with a fair degree of accuracy, by means of an eye-piece micrometer-scale. This is a ruled disc of glass that can be placed upon the diaphragm within the ocular, where its scale should be well defined when seen through the upper lens of the eye-piece. Special micrometer ocu- lars are made which permit of focussing the scale, but these are unnecessary if the diaphragms of the ordinary oculars are in the right places within the eye-piece tubes. The value of the divisions of the eye-piece micrometer-scale must be determined by comparing it with the scale of a micrometer-slide which is placed upon the stage of the microscope. These scales usually consist of 1 mm. divided into hundredths, and the eye-piece scale will have dif- MICROSCOPICAL TECHNIQUE. 399 ferent values for each combination of lenses used and for every variation in the length of the microscope-tube. The unit for micro- scopical measurements is one-thousandth of a millimeter, or one- millionth of a meter ; it is called a " micrometer," and is desig- nated by the Greek letter fi. One division of the micrometer-slide mentioned above would, therefore, equal 10 ft. From these data it is possible to calculate the value of each division of the eye-piece micrometer-scale in terms of [J. for each combination of lenses, the length of the microscope-tube being fixed. (Most Continental stands and many American stands have graduated tubes, and the objectives are constructed for a standard tube-length of 160 milli- meters.) It is well for the student to get into the habit of estimating the sizes of the objects he examines. A good standard for mental com- parison is the diameter of the unaltered red blood-corpuscle, which is about 7.5 p.. MICROSCOPICAL TECHNIQUE. Useful preparations for study under the microscope may be pre- pared from tissues in one of three ways : 1, simple scrapings of the tissues may be mounted on a slide in the fluids derived from the tissues themselves, or in a neutral solution — e. (/., 0.75 per cent, salt solution ; 2, the tissue-elements, cells, and intercellular fibres, etc., may be separated from each other by treatment with some macerat- ing-fluid — e. g., very weak chromic acid (1 : 10,000), 36 per cent, caustic potash, ^ alcohol ; 3, sections of the tissue may be prepared either while they are fresh, with a razor or a freezing-microtome, or after hardening. The first method has a limited application. It is serviceable only when the tissue-elements are so loosely held together that they readily separate from each other and can be examined in an isolated condition. This is the case with a considerable number of tumors, the superficial tissues of mucous membranes, the spleen, etc. If the inside of the cheek be scraped with the finger-nail, and the material thus removed be diluted with saliva, placed upon a slide, and covered with a cover-glass, the squamous epithelial cells lining the cavity of the mouth will be readily seen in an isolated state. An appropriate dye may now be introduced under the cover, and by its means the nuclei of the cells stained, thus bringing them into clearer view. 400 HISTOLOGICAL TECHNIQUE. When a simple scraping of the natural or freshly cut surface does not yield useful preparations, showing isolated tissue-elements, some process of maceration may be employed. Bits of the tissue are soaked for a time in some solution that serves to soften the cement- substances lying between the elements of the tissues, so that they may be easily separated with needles (teasing). Such specimens are usually best examined when mounted on a slide in some of the macerating-fluid. Man)- of the macerating-solutions not only favor the separation of the constituents of tissues, but also preserve them, so that a fair idea of their natural size and shape may be obtained from such preparations. It is evident, however, that with this method very little can be learned of their arrangement in the tis- sues before they were separated, and a knowledge of that arrange- ment is often of greater importance in the determination of the character of the tissue than a knowledge of the exact shape and size of the tissue-elements. The third method, that of preparing sections of the tissues, is the one most commonly employed, because it yields the most useful results. The structural elements composing the tissues are seen in their natural relative positions, and can be distinguished from each other and identified by the use of dyes and other reagents that affect them in some characteristic manner. But in order to ob- tain useful sections the tissues must almost always undergo some preliminary treatment with reagents, to give them a proper consist- ency for cutting and to hold the tissue-elements together so that the sections shall not fall apart after they have been cut. This may be accomplished by freezing the tissue before cutting it ; but more satisfactory results are obtained by causing a coagulation of the albuminous substances and subsequently extracting some or all of the water contained in the tissues. These changes in the tissues give them a firmness which favors the preparation of very thin sec- tions ; but sometimes even they are inadequate, and then the tissues are usually impregnated with some substance, like paraffin or col- lodion, which fills the interstices of the tissues and can then be hardened, when it serves to hold the tissue-elements together and retain them in their natural positions. The paraffin or hardened collodion is cut with the tissues and keeps the sections from disinte- grating. Before mounting the section, the substance used for im- pregnation may be removed from the section, or it may be retained MICROSCOPICAL TECHNIQUE. 401 permanently, since it is usually easily recognized in the specimen and does not interfere with its study under the microscope. The study of tissues by means of sections has the disadvantage that the elements of the tissues are cut, and the sections contain the resulting portions as well as complete elements. The incomplete portions lie near and at the surfaces of the sections, where they are in clearest view, while the uncut elements are situated in the body of the section, more or less obscured by the overlying portions that have been cut by the knife. Moreover, the tissue-elements may lie obliquely to the plane of the section, so that only a portion of them can be seen at a time, the rest being brought into clear view only when the focal plane is raised or lowered. These circumstances and the fact that the tissue-elements are frequently closely crowded together make the interpretation of sections a matter of some dif- ficulty in many cases. These difficulties are in a measure overcome by examining sections of different thicknesses, but a more satis- factory way of studying the structure of a tissue is to examine por- tions after maceration as well as in section. The processes of coagulation and dehydration, which have already been mentioned as usual preliminaries to the cutting of sections, deserve a few words in explanation of their purposes. The coagulation of the albuminous substances in the tissues has for its chief aim the preservation of the minute structure of the tissue-elements, so that a lapse of time or the subsequent manipula- tions of the tissues shall not cause an alteration in the details which it is desired to study. If this precaution be omitted, the tissues undergo post-mortem changes which seriously alter the appear- ance of the elements of which they are composed. Coagulation brought about for this purpose is called " fixation " of the tissues. It may be induced in a variety of ways : the tissues may be sub- jected to heat for a few moments, thus rendering the albumins they contain both solid and insoluble ; but the more usual procedure is to immerse the tissues in a solution of some substance that causes rapid death with coagulation. These solutions are called fixing- solutions, and not infrequently the substances they contain not only cause death and coagulation, but also form a union with some of the structural materials of the tissues which may facilitate their subsequent recognition. The number of formulae that have been devised for the prepara- tion of fixing-solutions is very great, and some of the solutions are 26 402 HISTOLOGICAL TECHNIQUE. better for the fixation of some tissues than for others. As a rule, those solutions that most perfectly preserve the finer intracellular details of structure have very little power of penetrating masses of tissue. They can, therefore, only lie employed when very small hits of tissue are to be fixed. Other fixing-solutions penetrate much better, but fail to fix the most delicate structures, which may undergo changes before they are preserved. It follows that the choice of the method of fixation must in each case depend upon the object to be attained. The removal of water from the fixed tissues is accomplished by means of alcohol. The fixing-agents are nearly all aqueous solu- tions, and while they increase the consistency of the tissues to a certain extent, they do not usually render them sufficiently firm for the preparation of thin and uniform sections. If the water in the tissues be replaced l>y alcohol, a greater and more uniform con- sistency is obtained, and the tissues are also partly prepared for impregnation with an embedding-material (collodion or paraffin) should that be necessary for section-cutting. After sections of fixed tissues have been obtained they usually require staining before they can be profitably studied. The chief reason for this will appear in the following explanation : When a specimen is examined under the microscope differences in structure among the colorless elements of the specimen may be seen, or differences in color between the different elements may be perceptible. We may, then, distinguish between a "structure- picture," due to differences that are not those of color, and a " color- picture," due solely to such differences. The manner in which the latter is produced is, perhaps, self-evident. The structure-picture is the result mainly of differences in refraction due to the various densities of different parts of the specimen. But the processes of fixation and hardening have for their purpose the rendering of the tissues of a relatively uniform density. They must, in consequence, tend to obliterate the details of the structure-picture which the sections yield when viewed under the microscope. For this reason the sections are stained, which converts the structure-picture into a color-picture. The substances composing the tissues have various affinities for dyes, and it is possible to take advantage of this in staining sec- tions, so that structures of the same nature shall receive one color, while those of different composition shall be dyed of a different METHODS OF FIXATION. 403 hue oi' an entirely different color. The coloring-matters, when so employed, not only bring out the structure of the tissue by creating a color-picture, but they also serve as valuable reagents in revealing the nature of the substances to which they impart a color. Again, it is often necessary that a certain method of fixation or other pre- liminary treatment should be used before the particular dye selected can display its greatest selective power for a particular substance. These facts explain the great number of formulae for stains and the preparation of specimens that are found in the technical text-books and journals. The subject has become so expanded within recent years that it has almost created a distinct branch of learning ; but it will only be necessary for the student of medicine to acquire a knowledge of a few methods that will serve to reveal the general structure of cells and the characters of the intercellular substances. The general outline of the procedures in common use for this pur- pose are as follows: 1, fixation; 2, hardening; 3, impregnation; 4, embedding ; 5, cutting ; 6, staining ; 7, dehydration ; 8, clearing ; 9, mounting. Some methods of preparation combine one or more of these steps in a single manipulation, thus considerably reducing the time requi- site for the completion of the process. Other methods necessitate the intercalation of still other manipulations, or the subdivision of those already enumerated. Methods of Fixation. 1. Miiller's Fluid. — This classic fixing- and hardening-solution con- sists of potassium bichromate, 2.5 per cent., and sodium sulphate, 1 per cent., dissolved in water (preferably distilled water). It is slow in action, requiring from six to eight weeks for the preservation of an average specimen, but with proper care can be made to yield excellent results when the finer details of structure are not to be studied. It is important to use large quantities of the fluid, at least ten times the volume of the tissues immersed in it, and to renew the fluid so frequently that its strength shall be constantly maintained. When fresh tissues are placed in Miiller's fluid they speedily render it cloudy. This is a sign that the fluid should be renewed, even if only an hour has elapsed since the tissues were placed in it. When cloudiness no longer appears the fluid should be renewed once a day for the first two weeks : after that, two or three times a week till the process is completed. 404 HISTOLOGICAL TECHNIQUE. After fixation in Miiller's fluid specimens should be washed in running water over night, or for twenty-four hours, and then hard- ened in alcohols of progressively greater strengths. While in the weaker alcohols specimens should be kept in the dark, to avoid the formation of precipitates, which occur under the influence of light. Pieces of tissue placed in Miiller's fluid should not be more than 1 om. in thickness. Two excellent modifications of Miiller's fluid have been devised by Zenker and Orth for the purpose of hastening the fixation and of securing a more faithful preservation of structural detail. 2. Zenker's Fluid. — Potassium bichromate, 2.5 grams. Sodium sulphate, 1 gram. Mercuric chloride, 5 grams. Distilled water, 100 cc. To this stock solution 5 per cent, of glacial acetic acid is to be added just before use of the fluid. Zenker's fluid fixes tissues in from three to twenty-four hours. The pieces should not be more than 5 mm. thick, and after fixa- tion should be washed for several hours in running water and then hardened in alcohol. This solution possesses the disadvantage that a precipitation of mercury or some mercurial compound is likely to take place within the tissues. This deposit may be, at least in great measure, removed from the tissues by adding a little tincture of iodine to the harden- ing-alcohols. The iodine combines with the mercury and produces a soluble compound, which is dissolved out by the alcohol. As the iodine disappears from the alcohol the latter becomes bleached, and fresh tincture must be added until the alcohol remains permanently tinged. If, after sections of the tissue have been prepared, they are found to contain a mercurial deposit, this can be removed by treatment with dilute iodine tincture or with Lugol's solution. 3. Orth's Fluid.— Potassium bichromate, 2. Sodium sulphate, 1 grams, gram. Distilled water, 100 cc. This stock solution is Miiller's fluid. Before use, 10 cc. of for- METHODS OF FIXATION. 405 maldehyde (40 per cent.) is to be added to every 100 cc. of the Muller's fluid. Orth's fluid fixes in three or four days. The pieces of tissue should not be more than 1 cm. thick. The time for fixation can be shortened if smaller pieces are used and the process is carried on at a slightly elevated temperature ; e. g., in an incubator kept at 37° C. (98.6° F.). After fixation the specimens should be washed in running water, as in the previous methods. 4. Mercuric Chloride Solution. — A saturated solution of corrosive sublimate in 0.5 per cent, salt solution is prepared by heating an excess of sublimate crystals in the salt solution and allowing the mixture to cool. The clear fluid is decanted from the crystals when desired for use. The penetration and action of the solution are favored by the addition of 5 per cent, of glacial acetic acid at the time of using. The thickness of the pieces of tissue should not exceed 5 mm., and much thinner pieces are better. Fixation takes place within six hours, after which the tissues may be washed in running water, or placed at once in 70 per cent, alcohol. If acetic acid has been used, it is best to wash in water before immersing in alcohol. Tincture of iodine should be added to the alcohol for the reasons given in the description of Zenker's fluid. 5. Formaldehyde. — This gas is capable of being absorbed by water to form a 40 per cent, solution, but its volatility renders such a solution liable to deterioration. The strength employed for fixa- tion is usually 4 per cent., and may be prepared by adding 10 cc. of 40 per cent, formaldehyde to 90 ec. of distilled water. A 0.75 per cent, solution of common salt may be substituted for the distilled water with possible advantage. Formaldehyde penetrates deeply and quickly into the tissues, which may be 1 cm. in thickness, and accomplishes fixation within twenty-four hours, but the preservation of structural detail is not very perfect. The solution is useful where the general characters of the tissues are to be determined and the details of the cells are of comparatively little consequence. After fixation the tissues may be washed in water, or placed directly in 70 per cent, alcohol ; or frozen sections may be at once prepared. Satisfactory sections may be obtained from small pieces of tissue if they are put in the for- maldehyde solution for an hour or two and then cut with the freezing-microtome. After they have been washed for a short time in water they may be stained by any of the more usual methods. 406 HISTOLOGICAL TECHNIQUE. 6. Flemming's Solution. — This is a solution containing osmic acid, chromic acid, and acetic acid. It does not keep well, and it is best to prepare it just before it is to be used. For this purpose the following stock solutions may be kept on hand : A. 2 per cent, solution of osmic acid in 1 per cent, chromic acid. B. 1 per cent, solution of chromic acid in distilled water. Osmic acid is sold in sealed tubes containing 1 gram. To prepare the stock solution " A," the tube should be washed on the outside and a deep file-scratch made near its centre. It should then be broken into a bottle containing 50 cc. of a 1 per cent, solution of chromic acid in distilled water. The halves of the tube should be dropped into the bottle and its contents shaken at intervals until solution is effected. This solution had best be kept in the dark to avoid decomposition of the osmic acid. When required for use, prepare the Flemming's solution by mixing : Solution " A," 4 cc. Solution "B," 15 " Glacial acetic acid, 1 " Flemming's solution is especially useful for fixing the finer details of structure within the cell. It was devised for the preservation of the mitotic figures formed during karyokinesis, but its range of usefulness far exceeds that limited application. Its power of pene- tration is very slight and the pieces of tissue selected for fixation must be small. They should not exceed 2 mm. in their least measurement, and thinner pieces are apt to give better results. Owing to the presence of osmic acid, Flemming's solution stains fat a dark-brown or black color, and may be used as a reagent for the identification of fatty substances. Tissues should be left in Flemming's solution for about twenty- four hours, though twice that length of time would cause little if any harm. They must then be thoroughly washed in running water for twenty-four hours or longer, and hardened in alcohol. Since Flemming's solution is usually employed for the study of the individual cells, it is desirable to prepare very thin sections of the tissues that have been hardened in it. For this purpose embedding in paraffin is the best method. The foregoing fixing solutions will meet most of the requirements of the practitioner of medicine, but it frequently happens that he METHODS OF FIXATION. 407 would like to obtain speedy results from a microscopical examina- tion without running the risk of loss of material or of poor results. When this is the case he may use absolute alcohol as a fixing-agent, thus taking advantage also of its ability to harden tissues and fit them for rapid embedding in collodion. 7. Absolute Alcohol. — If fresh tissues are placed in strong alcohol, say 95 per cent., they are hardened ; but during the process there is an opportunity for the albuminous fluids in the tissues to escape to a certain extent, and for shrinkage to take place in consequence. If absolute alcohol be employed, it causes such rapid coagulation that this leaching of the tissues does not take place. It is neces- sary, however, that the alcohol should remain of nearly its original strength, otherwise the water in the tissues will dilute it sufficiently to destroy this coagulating action. An excellent means for maintaining the strength of the alcohol is to immerse in it a few lumps of quick-lime. Take a small jar that can be hermetically closed by a tightly fitting cover (a museum jar, holding six or eight ounces, will answer). Place the lime in the bottom and then nearly fill with absolute alcohol. A few pieces of crumpled filter-paper are placed upon the lime and covered with a smooth piece placed so as to slant a little. The latter should lie near the surface of the alcohol, but be entirely sub- merged. Small pieces of the tissue to be fixed are placed upon the filter-paper where they will be covered by the alcohol. The alco- hol immediately coagulates the albuminous substances on the sur- face of the pieces and then gradually replaces the water in the specimen, coagulating the deeper-seated albumins as it penetrates the mass. The expelled water sinks to the bottom of the jar, owing to its greater specific gravity, and is at once taken up bv the lime. It is essential for the success of this method that the lime should be exceedingly quick. It must show immediate signs of slaking if even a drop of water be placed upon it. 1 It will be seen that this method not only fixes the tissues, but quickly dehydrates them. The real dehydrating-agent is, however, the lime, the alcohol serving merely as a vehicle for conveying the water from the specimen to the lime. If the pieces of tissue are 1 A jar of absolute alcohol, prepared as above, may be used for purposes of fix- ing or hardening until the lime has become slaked or the alcohol so impregnated with dissolved fat that the latter interferes with embedding in collodion. When the latter is the case the hardened collodion is opaque or opalescent. 408 HISTOLOGICAL TECHNIQUE. small, not over 5 mm. thick, they will be hardened by remaining in the absolute alcohol over night, and mounted sections may be ready for examination by the next afternoon. 8. Fixation by Boiling. — Throw small pieces of the tissue, not larger than 1 cm., into boiling 0.75 per cent, salt solution. Keep them at the temperature of boiling for two minutes. Then throw them into cold water. They may then be cut with the freezing- microtome, or may be placed in 70 per cent, alcohol for hardening. This method is excellent for the detection of albuminous exudates within the tissues, but it causes so much shrinkage that it is not useful for general purposes. Methods of Hardening. Solutions of chromates, as Midler's fluid, will, after a time, con- fer a pretty firm consistency upon tissues, and even render them brittle. Tissues fixed in corrosive sublimate are also very much hardened. But the usual practice is to harden specimens in alcohol after fixation. To obtain the best results this hardening should be done gradually, since immersion in strong alcohol is apt to produce undesirable shrinkage, affecting the various tissue-elements in dif- ferent degree. Seventy per cent, alcohol (736 cc. 95 per cent, alcohol to 264 cc. water) is weak enough to begin with. After the tissues have been in alcohol of that strength for twenty-four to forty-eight hours, accord- ing to the size of the pieces, they are placed in 80 per cent, alcohol (842 cc. 95 per cent, alcohol to 158 cc. water) for an equal length of time, and then in 95 per cent, alcohol. From the 95 per cent, alcohol they are placed in absolute alcohol, if it be desired to embed them in either collodion or paraffin. If they are not intended for immediate use, they may be kept indefinitely in 80 per cent, alcohol. During the hardening it is best not to allow the tissues to rest on the bottom of the vessel containing the alcohol, as they are liable to slight maceration in the alcohol, which there becomes diluted with water from the specimen. They can be kept off the bottom by means of a little crumpled filter-paper. Specimens that have been fixed in a chromate solution should be kept in the dark while being hardened; those that have been fixed in corrosive sublimate should be hardened in alcohols to which a little tincture of iodine (sufficient to give them a sherry color) has been added. "When absolute alcohol is used, its strength should be maintained by con- METHODS OF I3IP11EQSATI0N. 409 tact with quick-lime (see directions for fixing tissues in absolute alcohol). Methods of Impregnation. When tissues are so porous or friable that sections are likely to tear or disintegrate it is desirable to impregnate them with some embedding-material. The most useful substances for this purpose are collodion, or celloidin, and paraffin. Whichever of these is used, it is necessary to remove the water from the specimen before the impregnation can be accomplished, for both collodion and paraffin are insoluble in water. Tissues that have been hardened in alcohol are to a certain extent already dehydrated. The residual water may be removed or reduced to a trace by treatment with absolute alcohol, in which collodion is soluble. The " celloidin " manufactured by Schering is an excellent prep- aration of gun-cotton, but almost equally good results may be obtained by using the more economical soluble cottons employed by photographers. Two solutions in a mixture of equal volumes of ether and absolute alcohol (both, if possible, of Squibb's prepara- tion) should be kept in stock : one, a weaker solution, having about the consistency of thin mucilage ; the other, a stronger solution, resembling a syrup. Collodion is soluble in absolute alcohol, so that tissues containing only that fluid are ready for impregnation without further prelim- inary treatment. When thorough impregnation is desired the tissues should be immersed in equal parts of ether and absolute alcohol for a few days, and then in the weaker solution of celloidin or collodion for a number of days or weeks — the longer the better; 1 but such complete impregnation is often unnecessary, and soaking for a day or two will often suffice if the sections to be made need not be very thin. It is not possible, in any event, to make very thin sections from tissues embedded in collodion ; but sections of large area may be obtained, which is often of greater importance. For very thin sections it is better to use paraffin for the embedding-material, although the resulting sections will have to be smaller. Paraffin is insoluble in alcohol of all strengths. It is therefore necessary to remove the absolute alcohol from the tissues before they can be impregnated with paraffin. This may be done by immersing the tissues in some liquid that is a solvent for paraffin 1 Impregnation may be greatly hastened if done at the body-temperature in a. hermetically closed vessel. 410 HISTOLOGICAL TECHNIQUE. and is also miscible with alcohol. For this purpose, xylol, chloro- form, or oil of cedar-wood may be used. Xylol yields the most rapid results, but its use is contraindicated when it is desired to retain fatty substances that have been colored with osmic acid, as the xylol extracts them. If their preservation within the tissues is important, chloroform should be used; but the sojourn even in that liquid should be as short as possible. Oil of cedar-wood prob- ably causes less change in tissues than chloroform, but the method is more protracted, and, requiring longer treatment in the paraffin- oven, probably has little ultimate advantage over chloroform for general purposes. If xylol is used, the tissues are transferred from the absolute alcohol to xylol, on which they at first float. Subsequently they sink, and are gradually rendered transparent as the alcohol is expelled by the xylol. When there are no opacities left the speci- men is ready for the paraffin-oven. These changes take from two to twenty-four hours. The treatment with chloroform is similar to that with xylol, but after the tissues have been cleared in chloroform (six to twenty-four hours) they are immersed in a saturated solution of paraffin in chloroform for about the same length of time. They are then ready for the paraffin-oven. AVhen oil of cedar-wood is used the pieces should be soaked in two successive portions of the oil, about twelve hours in each, to insure removal of the alcohol. The foregoing steps are all preliminary to the actual impregnation with paraffin. It is important that the paraffin used for impregnation and embedding should have a wax-like, and not a crystalline, texture, and that its melting-point should be such that its consistency will be favorable for cutting at the average temperature of the labora- tory. Grubler, of Leipzig, furnishes excellent qualities of paraffin. For a room-temperature of 20° C. (68° Fah.) a variety melting at 50° C. (122° Fah.) will give good results. If the laboratory is warmer, a paraffin of higher melting-point should be used. Impregnation is accomplished by placing the bits of tissue in a bath of melted paraffin maintained at a temperature only slightly above that of fusion, say 52° C. (125.6° Fah.), if the paraffin melts at 50° C. (122° Fah.). This may be accomplished in a water- jacketed oven provided with a thermoregulator, or upon a plate of METHODS OF EMBEDDING. 411 brass or copper, resting on a tripod and heated at one end by a burner. When the latter method is employed the paraffin is melted in a little glass dish, which is moved along the plate until a point is found at which the paraffin remains melted at the bottom, but is covered at the edges of the surface with a thin layer of congealed paraffin. The length of time that the specimens should remain in the melted paraffin will vary with the character of the tissues and the method of getting rid of the alcohol which has been employed. It should not be protracted longer than necessary for complete impreg- nation, as heat is injurious to the tissues. When xylol has been used two hours will usually suffice if the pieces of tissue are small, and especially if they are transferred to a fresh paraffin-bath after about an hour. This renewal of the paraffin is still more important if oil of cedar-wood has been used. Chloroform requires a little more time than xylol, and should be transferred to fresh paraffin once or twice. When impregnation has taken place and the final bath of paraffin no longer has the slightest odor of the clearing-agent the pieces of tissue are removed from the bath with warmed forceps and placed on bits of writing-paper, to which they adhere. A designation of the specimen may be written on these papers, and the tissues kept in this condition until required for cutting. They must then be embedded. Methods of Embedding. The object of embedding is to surround the piece of tissue from which sections are to be cut with a mass of the embedding-sub- stance, which then not only supports the tissue when it comes in contact with the knife, but also affixes it to a block or other support which can be fitted into the clamp of the microtome. Microtomes designed for cutting paraffin usually have special supports for the embedded specimen, but blocks of hard wood may be used in their place. For the support of tissues embedded in collodion blocks of plate- glass are probably both better and cheaper than those made of other materials. They may be easily prepared from waste pieces of plate- glass, about a quarter of an inch thick, and " obscured " or ground on one surface. The glass may be cut into blocks of any desired size by scoring the smooth side with a diamond and then splitting the pieces apart with a sharp blow from a wedge-shaped hammer. The em- 412 HISTOLOGICAL TECHNIQUE. bedded specimen is affixed to the rough surface of these blocks by means of collodion, and the blocks may be numbered with a lead pencil upon the rough surface. The writing will be preserved from obliteration by the specimen subsequently placed upon it, and can be read through the glass. 1. Embedding in Collodion (or Celloidin). — Tissues of firm con- sistency and moderately uniform structure, such as liver, kid- ney, and the majority of tumors which have been hardened, may be embedded without previous impregnation. Before this can be done, however, they must be either dehydrated with abso- lute alcohol, or soaked for a few hours in a mixture of equal volumes of ether and alcohol (95 per cent, alcohol will answer, if absolute alcohol is not to be had). For this rapid method the bottom of the piece of tissue must be flat and parallel to the plane of the desired sections. When the necessary trimming of the speci- men is completed moisten it with absolute alcohol or the ether- alcohol mixture, then dip it in the thick solution of gun-cotton and place it at once upon the ground surface of the glass block (pre- viously labelled). In a few minutes the collodion will have evap- orated sufficiently for the formation of a distinct pellicle upon its surface. "When this has become firm enough to withstand gentle pressure immerse the block and specimen in several times their vol- ume of .SO per cent, alcohol. This will harden the collodion, and in the course of a few hours the specimen will be ready for cutting. Tissues impregnated with collodion had best be embedded by a slower process than the foregoing, although that method will answer where only a slight support of the tissue-elements within the speci- men is needed. A gradual concentration of the collodion within the tissues may be brought about in the following manner : Smear the inside of a small, straight-sided glass dish with a trace of glycerin and then fill it with enough moderately thick collodion to cover the pieces of tissue with a layer about one-quarter of an inch deep. Now place the specimens that have been in thin collo- dion in the dish, with the surfaces from which sections are to be cut resting on the bottom. Place the dish in a larger vessel with higher sides and loosely cover the latter. The ether and alcohol in the collodion will gradually evaporate, and their vapors will first fill the outer vessel and then overflow its sides. The depth of the outer vessel keeps these vapors in contact with the surface of the collo- dion, preventing the formation of a pellicle, which would retard METHODS OF EMBEDDING. 413 evaporation and also favor the formation of bubbles in the collo- dion. After an interval of one or more days the collodion will have a gelatinous consistency. It should be allowed to become so hard that it has considerable firmness, but is still soft enough to receive an impression of the ridges in the skin when pressed with the finger. The outer vessel is then partly filled with 80 per cent, alcohol so that the whole of the inner dish is submerged. By the next day the collodion will be hard enough for removal from the dish. With a small scalpel, held vertically, divide the hardened mass of collodion into portions, each of which contains one of the pieces of tissue (for several pieces may be embedded in the same dish, provided care be taken to preserve their identity). Remove the pieces and trim down the collodion around the speci- mens, leaving a margin of about an eighth of an inch. Trim the top surfaces of the collodion parallel with the bottom surfaces, then dip the trimmed surface into a little absolute alcohol contained in a watch-glass, in order to dehydrate it. This will take about two minutes. Label glass blocks with lead-pencil, place a drop of thick collodion on the writing, and transfer the embedded specimens immediately from the absolute alcohol to the drop of collodion, pressing it into contact with the glass. When a good pellicle has formed on the collodion drop the whole block into 80 per cent, alcohol. If the block of hardened collodion containing the speci- men be sufficiently dehydrated on the surfaces coming in contact with the drop of collodion, and the latter have not time for the formation of a pellicle before it receives the block, there will be no difficulty in cementing the embedded specimen to the roughened surface of the glass. It is best not to cut sections until the day after the specimen has been affixed to the glass block. These blocks, with attached specimens, may be preserved indefinitely in 80 per cent, alcohol. The thin coating of glycerin on the inside of the embedding-dish serves the purpose of preventing the collodion from sticking to the glass. 2. Embedding in Paraffin. — The specimen should first be trimmed so as to have one surface parallel to the plane of the future sections. If it is surrounded by too much paraffin to permit of ready inspec- tion, it may be placed on a piece of filter-paper and warmed until the superfluous paraffin is absorbed by the paper. The trimmed surface is then laid upon a small glass plate that has been smeared 414 HISTOLOGICAL TECHNIQUE. with a mere trace of glycerin, and metallic right-angles, similarly- smeared on the inside, are placed around the specimen in such a way as to form a box with a clear space at least an eighth of an inch broad between its sides and the specimen. Melted paraffin, at a temperature only slightly exceeding that necessary to keep it fluid, is then poured into the box, filling it. The paraffin should now be made to cool as rapidly as possible, in order to prevent its becoming crystalline. For this reason it is well to prepare the box formed by the plate of glass and the metallic right-angles in the bottom of a deep soup- plate or some similar vessel. After the box has been filled with melted paraffin cold water may be poured into the plate until its surface is nearly on a level with the top of the box-, and when the top of the paraffin has congealed the plate may be filled with cold water. After a few minutes the box may be taken apart and the block of paraffin left in the water to become cold. These paraffin-blocks may be labelled with a needle and kept indefinitely in the dry condition, at a temperature below that at which the paraffin softens. When they are to be used the bottom of the block should be trimmed parallel with the top, sufficient paraffin being removed to obliterate the hollow which formed when the paraffin solidified. This trimmed surface is then made to ad- here to the paraffin-support of the microtome, or a block of hard wood, by means of a heated scalpel. It often happens that little air-bubbles are present in the paraffin close to the specimen, or that cracks exist between the specimen and the surrounding paraffin, owing to the retention of a little air at the time of embedding. These defects can be remedied bv melt- ing the paraffin with a heated needle. It is important that the paraffin should everywhere be in perfect contact with the specimen. When this repairing, if necessary, has been done and the paraffin has become cold again, the block should be trimmed so that the specimen, or at least its upper part, is contained in a little cubical mass resting on the main block, with a margin of paraffin, about 1 mm. thick at the places where the edges of the cube are nearest to the specimen. Those edges should be straight and at right angles to each other, and the sides of the trimmed cube should be vertical. In trimming the block only thin slices should be removed at a time, in order to avoid cracking the paraffin forming the small cubical mass enclosing the specimen. These manipulations prepare the specimen for cutting. METHODS OF CUTTING. 415 Methods of Cutting. It is possible to obtain useful sections from fresh or hardened tissues by free-hand cutting with a sharp razor ; for this purpose the razor should either be very hollow ground, so as to have a thin blade, or the lower surface should be ground flat. In stropping the razor, or microtome-knife, the stroke should be from point to heel during both the forward and return motions. In cutting, the edge should be used from heel to point, and this same motion should be used in honing. A wire arrangement is usually furnished with microtome-knives, which is intended for use while honing or stropping. It serves to raise the back of the knife when the flat side is sharpened, and should always be employed. Care must be taken not to press the knife against the strop, as this is liable to turn or blunt the edge. A few light strokes on the strop immedi- ately after each day's use will keep the knife sharp and coat it with a little grease, protecting it from rust. A microtome-knife should never be allowed to rest with its edge on any hard surface ; the mere weight of the knife is sufficient to spoil its edge. In cutting free-hand sections of fresh tissues the upper surface of the razor should be kept flooded with normal (0.75 per cent.) salt solution. The sections float in this fluid and are kept from tearing. Each section should be removed by a single stroke of the razor. When hardened specimens are cut, 80 per cent, alcohol should be used instead of salt solution. Free-hand sections cannot be made either so thin or uniform as sections prepared with a microtome, and these instruments are now so cheap that they are universally used. There are three principal forms: 1, freezing-microtomes ; 2, paraffin-microtomes; 3, micro- tomes for cutting sections of tissues embedded in collodion. The last are often fitted with attachments intended for use in cutting frozen sections, and can also be used for paraffin. But the best results are obtained by using instruments especially designed for each purpose. 1. Frozen Sections. — Freezing is usually employed when sections of fresh tissues are to be made, but hardened tissues may be cut with a freezing-microtome if the alcohol be first removed by soaking for a considerable time in water. The tissue may be placed upon the plate of the microtome in a little water or neutral salt solution ; but a better method is first to soak the tissue in a syrupy solution of 416 HISTOLOGICAL TECHNIQUE. gum-arabic, and to moisten the plate with the same before freezing. This solution freezes in less coarsely crystalline form than water or salt solution. "When the tissues are frozen, thin sections are removed with a quick forward and slightly oblique stroke of the knife. The motion is intermediate between that of a plane and a single stroke of a saw. The sections are floated from the knife in a dish of water or normal salt solution ; or they may be fixed in a 4 per cent, solution of for- maldehyde. The frozen tissue must not be too hard. Should that be the case, the upper surface may be moistened by means of a camel's-hair brush, dipped in water or salt solution, or warmed with the breath. 2. Collodion-sections. — The block upon which the embedded speci- men is fastened is secured in the clamp of the microtome in such a position that the sections will be made in the desired plane. The knife is then adjusted on its carrier in an oblique position, so that the greatest possible length of its edge will be utilized in cut- ting. The upper surface of the knife is flooded with 80 per cent, alcohol, and slices are removed with the knife until the desired level of the specimen has been reached. Sections are then made as thin as is compatible with obtaining complete sections from the whole surface. The sections float in the 80 per cent, alcohol, with which the knife should be kept flooded, and may be removed with a camel's-hair brush. At no time should either the knife or the specimen be allowed to dry. The sections may be kept indefinitely in 80 per cent, alcohol, or they may be dropped into water if they are to be used within a short time. After use, the knife should be carefully wiped, stropped, and placed in its case. The microtome should be dried and the tracks moistened with a little oil of sweet almonds or paraffin oil, to prevent rusting. 3. Paraffin-sections. — The knife should be fixed perpendicular to the direction of cutting, its edge acting like that of a plane. Its surfaces must be clean and dry ; adherent paraffin can be removed with a cloth moistened with xylol. The paraffin-block containing the specimen to be cut is firmly clamped with one of its narrow edges parallel to the edge of the knife. The block is now raised and moderately thick slices re- moved until the desired level is reached, when the thin sections desired may be cut. It not infrequently happens that the sections roll before the edge of the knife. This is probably due to the METHODS OF CUTTING. 417 paraffin being too hard. In that case the cutting should be done in a warmer room. This rolling will, however, cause little trouble in the use of the sections unless it be desired to have them adhere to each other at the edges to form ribbons, in which the succession of the sections is preserved. Before paraffin-sections can be stained it is necessary to remove the paraffin. If the tissues are sufficiently coherent, this can be done by dropping the sections into xylol or chloroform ; but if this would cause a disintegration of the sections, they must be affixed to slides or cover-glasses by means of a cement which shall hold the dif- ferent parts of the tissues in their proper relative positions after the paraffin has been removed. The simplest cement for this purpose is Mayer's albumin mixture, prepared as follows : beat up the white of an egg and allow the froth to liquefy. Then add an equal bulk of glycerin and a few pieces of camphor (for the preservation of the mixture). This cement is applied to the clean surface of a slide, or, better, a cover-glass, in a very thin layer with the side of a camel's-hair brush, care being taken to leave no air-bubbles. The paraffin-sections are removed from the knife with a fine camel's-hair brush or a small, but rather stiff, feather inserted into a handle, and placed upon the coating of cement. They are then flat- tened out with the brush or feather and pressed against the glass to remove superfluous cement. If the sections have rolled, unrolling will be facilitated by warming the sections with the breath. The cover- glasses are set aside to dry a little, and are then heated to render the albumin insoluble. This requires some practice. The manipu- lation is intended to accomplish the following results : the paraffin melts at a lower temperature than that at which the albumin is coagulated, and this fact is utilized to remove all excess of the cement, which is washed away from the tissues by the flow of melted paraffin. The residual albumin is sufficient to make the section adhere to the glass when subjected to a high enough temperature to cause its coagulation. The albumin should be dried to a consider- able extent before it is converted by the heat into its insoluble form, otherwise it will coagulate in opaque masses. To bring about the desired results the cover-glass, held in a pair of forceps, is waved over a flame until the paraffin is seen to melt. That tempera- ture is maintained for a few moments, and then the cover-glass is heated until vapors are distinctly seen to rise from its surface. Great care must be taken not to scorch the sections. When the 27 418 HISTOLOGICAL TECHNIQUE. sections have been cemented to them the cover-glasses are placed in absolute alcohol to dehydrate them, and are then treated with xylol, chloroform, or some other solvent of paraffin. The solvent is then removed by another bath of absolute alcohol, and the alcohol removed by water, when the sections are ready for staining. When the sections do not require affixing to cover-glasses they may be dropped into the solvent for the paraffin, and the latter removed with absolute alcohol, for which water is then substituted, preparing the sections for staining. It sometimes happens that when sections are transferred from absolute alcohol to water the diffusion-currents are so strong that the sections are destroyed. "When this is the case the transition must be made more gradually, baths of 80 per cent., 50 per cent., and 30 per cent, alcohol being interposed between the absolute alcohol and the water. Methods of Staining. A large number of methods have been devised for bringing out the structure of tissues. Many of the methods are of almost uni- versal application, while others require special methods of fixa- tion or other preliminary treatment of the tissues. Some are calcu- lated to render the general features of structure more evident than they would be if the tissues were not stained ; others stain certain elements some characteristic color, and, to that extent, serve the purpose of microchemical reagents. Only a few of the more useful methods can be described here ; for others the reader is referred to the larger text-books and the technical journals. 1. Hematoxylin and Eosin. — Hematoxylin, the coloring-principle of logwood, has proved a very useful stain for the nuclei of cells. It is not a pure nuclear stain, but also tints the cytoplasm of cells and the intercellular substances. It is most commonly employed in combination with alum. Such combinations of coloring-matter with a base are called " lakes." A hsematoxylin-lake may be used alone, or its use maybe preceded or followed by the employment of a counterstain with some diffuse color not affecting the nuclei. For countcrstaining, eosin or neutral carmine is usually employed. Both stain the tissues a diffuse red, varying in depth according to the nature of the tissue-elements in the section. There are several formulae for the preparation of alum-hsema- METHODS OF STAINING. 419 toxylin, but that devised by Bohmer will answer all purposes, and is very simple : 1. Hsematoxylin crystals, 1 gram. Absolute alcohol, 10 cc. 2. Alum, 20 grams, Distilled water, 200 cc. Cover the solutions and allow them to stand over night. The next day mix them and allow the mixture to stand for one week in a wide-mouthed bottle lightly plugged with cotton. Then filter into a bottle provided with a good cork. The solution is then ready for use. Nearly all solutions of alum-hsematoxylin require an interval of time for " ripening," and their staining-powers improve with age. Alum-hsematoxylin is intended for staining sections from tissues that have been fixed and hardened. It is especially useful when the fixing-solution employed contained chromates, but may be used after almost any method of fixation, if the time of staining is of the right length and the sections are previously freed from acidity by thorough washing. If the following directions are closely adhered to, the student can hardly fail to obtain good results in the use of Bohmer's hsematoxylin : Transfer the sections from the 80 per cent, alcohol in which they have been kept to a dish of distilled water. At first they will float on the surface of the water ; this is a favorable moment for removing all folds and wrinkles. The sections should be manipulated with platinum needles, prepared by fusing a bit of platinum wire into the end of a glass rod. Such needles can be cleaned by heating the wire red in a flame. When the sections sink to the bottom of the dish of water, and remain there, it may be assumed that they are free from alcohol. Filter about 5 cc. of the hsematoxylin into a watch-glass or butter- dish and transfer the sections from the water to the dye. Let the sections stain for three minutes by the watch, and then transfer them to a dish of distilled water. At first the sections will have a reddish tint, but as the washing proceeds the color will turn to a pure blue. During the washing the water should be renewed, until finally it acquires no color from the sections and the latter 420 HISTOLOGICAL TECHNIQUE. have lost all traces of a red tint. This washing may take several minutes, or even a few hours ; but if good, permanent stains are desired, it is of great importance that it be thorough. This wash- ing completes the actual staining with hsematoxylin, and the sections are then ready for counterstaining with eosin or for dehydration. The eosin solution used for diffuse staining is prepared by dis- solving 1 gram of eosin in 60 cc. of 50 per cent, alcohol. Of this solution, about ten drops are added to 5 cc. of distilled water in a small dish ; the sections are stained for about five minutes and then washed in distilled water. They are then ready for dehydration and mounting. The diluted eosin should be thrown away after use, but the hsematoxylin can be filtered back into the stock-bottle. Since the hsematoxylin solution improves with age, no exact directions can be given as to the length of time sections should remain in a particular solution. Three minutes will usually yield good results ; but if it is found that the color is too dark, a shorter time should be employed, and vice versd. One soon becomes famil- iar with the staining-pc iwers of the particular solution used. The dishes that have contained hsematoxylin should be washed soon after use, or may be subsequently cleaned with a little hydrochloric acid, all traces of which should then be removed by thorough wash- ing in water. The above method for staining with hsematoxylin and eosin is highly recommended for general routine work. 2. Neutral Carmine. — Carmine, "No. 40," 1 gram. Distilled water, 50 cc. Ammonia, 5 " The solution is allowed to remain exposed to the air until the odor of ammonia is no longer perceptible. It is then filtered into a bottle, where it is kept till needed. Neutral carmine gives a diffuse stain, resembling that of eosin, but rather clearer in character. It is employed in a greatly diluted form, according to the following directions : One drop of the neutral carmine is mixed with about 20 cc. of distilled water. A trace of acetic acid is then added by dipping a platinum needle into the acid and stirring the diluted dye with the acidulated needle. A piece of filter-paper is then placed upon the METHODS OF STAINING. 421 bottom of the dish, and the sections to be stained are transferred from distilled water to the dye and distributed upon the paper in such a way that they do not lie over each other. The dye acts very slowly, twenty-four hours being none too long for good results. If the staining be hastened by using a stronger solution, it suffers in sharpness. After staining, the sections are thoroughly washed in distilled water, and may then be subjected to a nuclear dye, such as hsematoxylin. The proper acidulation of the diluted dye is of importance for the success of this method. If the solution is not sufficiently neutralized, the sections will not be stained ; if it is too acid, precipitation of the carmine will take place. 3. Alum-carmine. — Alum, 5 grams, Distilled water, 100 cc. Carmine, " No. 40," 2 grams The alum is dissolved in the water with the aid of heat, the carmine then added, and the mixture kept at the boiling-point for about half an hour. It is then allowed to cool and filtered into the stock-bottle. Two or three drops of deliquesced carbolic acid may be added to prevent the development of fungi. Sections are stained in the undiluted, but filtered, dye for at least five minutes. There is no danger of over-staining. It is a pure nuclear stain, coloring the chromatin red. After staining, the sec- tions are either washed, and are then ready for dehydration, or they may receive a counterstain with picric acid, coloring the tissues a diffuse yellow. This may be most readily accomplished by adding a few small crystals of picric acid to the first dish of dehydrating alcohol (see p. 428). 4. Borax-carmine. — Borax, 4 grams, Distilled water, 100 cc. Carmine, " No. 40," 3 grams. Alcohol, 70 per cent., 100 cc. The borax is dissolved in the water by warming, and the solution allowed to cool ; the carmine is then stirred in and the alcohol added. After standing twenty-four hours the solution is filtered into the stock-bottle, a process that is exceedingly slow. 422 HISTOLOGICAL TECHNIQUE. Borax-carmine is used for the staining of little masses of tissue before they are embedded. It is a nuclear dye, giving the chromatin a red color. It is useful when paraffin-embedding is to be employed and it is desirable to restrict the manipulation of the sections to a minimum. Small pieces of hardened tissues, not over 5 mm. thick, are trans- ferred from distilled water to the undiluted dye and allowed to stain for twenty-four hours, or longer. After staining they are immedi- atelv placed in an acid alcohol, prepared by adding 5 drops of con- centrated hydrochloric acid to 100 cc. of 70 per cent, alcohol. The tissue should not rest on the bottom of the vessel containing the alcohol, but upon crumpled filter-paper, so that the extracted excess of coloring-matter may sink to the bottom. If the acid alcohol around the specimen becomes colored, fresh portions of alcohol should be used. The treatment with acid alcohol is continued until no more color is given off from the specimen. It is then transferred to 90 per cent, alcohol, in which it should remain for twenty- four hours, after which it can be subjected to the dehydration neces- sary for embedding. 5. Orth's Litliio-carmine. — Carmine, " No. 40," 3 grams. Lithium carbonate, saturated aqueous solution, 100 ec. The solution of lithium carbonate is prepared by occasionally shaking a mixture of distilled Mater and an excess of lithium car- bonate. Twenty-four hours will suffice for the production of a strong enough solution. The supernatant liquid is then filtered. Carmine readily dissolves in this solution. For preservation a crystal of thymol may be added. Lithio-carmine stains sections in about five minutes, and there is no danger of overstaining. Like borax-carmine, it requires after- treatment with acid alcohol. The sections should be transferred, without intermediate washing, to 70 per cent, alcohol containing 1 per cent, of concentrated hydrochloric acid ; they may then be de- hydrated, and, if desired, counterstained with picric acid during the dehydration. 6. Unna's Methylene -blue. — Methylene-blue, 1 gram. Potassium carbonate, 1 " Distilled water, 100 cc. METHODS OF STAINING. 423 When required for use, this solution should be diluted with dis- tilled water to about one-tenth of its strength. It is a good stain for bacteria, and may also be used for staining the nuclei of tissues either by itself, or after using eosin as a diffuse stain. An aqueous solution of eosin, 5 per cent., is used for this purpose, the sections being stained for about five minutes. They are then washed to remove the excess of eosin, and stained in the diluted methylene- blue for about an hour. After this they are again washed and treated with absolute alcohol, which discharges the excess of blue. They are then cleared with xylol and mounted in- dammar or Canada balsam, dissolved in xylol. The preliminary staining with eosin may be omitted, when a contrast- or counterstain is not required. 7. Aqueous Methylene-blue. — This is usually prepared at the time when heeded by mixing one part of a saturated solution of the ani- lin-color in 95 per cent, alcohol with nine parts of distilled water. It is frequently employed as a general stain for bacteria. Other anilin-colors, such as fuchsin, gentian-violet, methyl-violet, and Bismarck-brown, may be kept in concentrated alcoholic solu- tion, to be diluted in a similar manner just before use. When these solutions are used for staining sections or cover-glass preparations the adherent dye is washed off with water, after which the intensity of the stain is reduced by the use of alcohol, 95 per cent, or abso- lute, which bleaches the portions of the specimen which retain the color with the least tenacity. If the action of the alcohol be main- tained for too long a time, the color may be discharged from all parts of the specimen. The method of overstating a specimen, and then discharging the color from those parts where it is not de- sired, is a common one. The process of discharging the color is called the " differentiation " of the stain, because it serves to dis- tinguish those elements which hold the color strongly from those which part with it easily. 8. Carbol-fuchsin. — Saturated alcoholic solution of fuchsin, 10 cc. Aqueous solution of carbolic acid crystals, 5 per cent., 90 cc. This solution should always be carefully filtered before use. 9. Anilin-gentian-violet. — A. Ehrlich's formula : Saturated alcoholic solution of gentian- violet, 1.5 cc. Freshly prepared anilin-water, 8.5 cc. 424 HISTOLOGICAL TECHNIQUE. The anilin-water is prepared by shaking a few drops of anilin with distilled water, allowing the mixture to stand for about ten minutes, and then filtering through weli-moistened filter-paper. The filtrate should contain no globules of the anilin. In order to avoid this the filtration should be stopped before all the watery part of the mixture has run through the paper, otherwise oily drops of anilin will follow. Precipitates are likely to occur in this gentian-violet solution when it is first prepared. After twenty-four hours these are less abundant. The solution deteriorates soon after that time, and should not be used more than a week after its preparation. B. Stirling's formula : Gentian-violet, 5 grams. Alcohol, 10 cc. Anilin, 2 cc. Distilled water, 88 cc. This solution keeps better than the preceding. Both must be filtered carefully through moistened filter-paper immediately before being used. 10. Gram's Solution. — This is a differentiating agent used in con- nection with anilin-gentian-violet : Iodine, 1 gram. Potassium iodide, 2 grams. Distilled water, 300 cc. The specimens are first overstained with the gentian-violet solu- tion. They are then washed in water and placed in Gram's solution for from three to five minutes. While in this solution they turn a brown color, and the combination between the coloring-matter and some of the elements of the specimen is loosened. The specimen is then transferred to 95 per cent, alcohol, in which it remains until no more color is given off. If sufficient color has not been removed, the treatment with Gram's solution and alcohol may be repeated. After this differentiation the specimen may be dehydrated, cleared, and mounted ; or a contrast-stain may be used before those manipu- lations. This is a useful method for staining bacteria in sections of tissue when the species of bacteria are such as resist the decolor- izing action of the iodine. In this respect different species of bac- METHODS OF STAINING. 425 teria differ greatly, and the method is commonly employed in bac- teriological work to distinguish those species which retain the stain, or are " positive to Gram," from those which are decolorized or " negative to Gram." 11. Van Giesson's Picric Acid and Acid Fuchsin Stain. — Aqueous solution of acid fuchsin, 1 per cent., 5 cc. Saturated aqueous solution of picric acid, 100 " This solution serves to stain fibrous intercellular substances. It is used in the following manner : 1. Slightly overstain with alum hematoxylin ; e. g., Bohmer's hematoxylin. 2. Wash thoroughly in distilled water. 3. Stain in Van Giesson's dye for five minutes. 4. Wash in water. 5. Dehydrate in 95 per cent, alcohol. 6. Clear in oil of origanum. 7. Mount in xylol-balsam or xylol-dammar. The tissues should have been fixed in a corrosive-sublimate solu- tion or one containing chromates ; e. g., M tiller's fluid, Zenker's fluid, or sublimate solution. The connective-tissue fibres are stained red by the acid fuchsin. The reason for overstaining with hema- toxylin is that subsequent treatment with picric acid discharges some of that color. 12. Benda's Iron-haematoxylin Stain. — This is a powerful stain well adapted to the staining of paraffin-sections that have been affixed to cover-glasses. It stains nuclei and intercellular sub- stances, as well as the protoplasm of cells, various shades of gray, and the color is very permanent. The outline of the method is as follows : 1. Mordant the sections (after affixing to cover-glasses, if that method is used) in a mixture of equal parts of liquor ferri sul- furici oxydati of the German Pharmacopoeia and distilled water for twenty-four hours. 2. Rinse in distilled water, and then wash in three changes of tap-water. 3. Stain in aqueous solution of hematoxylin, prepared by mix- ing 10 drops of a concentrated alcoholic solution of the crystals with 10 cc. of distilled water. Stain for from one-half to twenty- four hours. 426 HISTOLOGICAL TECHNIQUE. 4. Rinse in distilled water. 5. Differentiate in equal parts of glacial acetic acid and distilled water. 6. Wash thoroughly in distilled water. 7. Dehydrate in absolute alcohoL 8. Clear in xylol, carbol-xylol, or some essential oil. 9. Mount in balsam. 13. Pal's Modification of Weigert's Stain for the Medullary Sheath of Nerves. — This method is useful for the study of the central ner- vous system, and may, with advantage, be preceded by staining with neutral carmine. The tissues should have been fixed in a chromate solution; e.g., Miiller's fluid. 1. Soak sections several hours in 1 per cent, chromic acid solu- tion in water. 2. Stain twenty-four to forty-eight hours in ; Hematoxylin crystals, 1 gram, Absolute alcohol, 10 cc. Lithium carbonate (saturated aqueous solution), 7 " Distilled water, 90 " The hymatoxylin crystals may be dissolved in the alcohol and the solution kept in stock, the proper proportions of lithium carbon- ate solution and water being added at the time of use. 3. Wash in water to which a little lithium carbonate solution has been added (about 2 cc. to each 100 cc. of water). The sections should acquire a deep-blue color. 4. Differentiate in 0.25 per cent, solution of potassium perman- ganate in distilled water, till the gray matter — e. g., of the spinal cord — becomes brownish-yellow (one-half to five minutes). 5. Decolorize the gray matter in the following solution : Oxalic acid, 1 gram, Potassium sulphite, 1 " Distilled water, 200 cc. 6. Wash thoroughly in distilled water. 7. Dehydrate in 95 per cent, alcohol. 8. Clear in carbol-xylol, oil of bergamot, or oil of origanum. 9. Mount in xylol-balsam or xylol-dammar. This method stains the myelin-sheaths of the medullated nerve- METHODS OF STAINING. 427 fibres a dark blue, nearly black, color. If it has been preceded by a stain with neutral carmine, the axis-cylinders of the nerve-fibres will be stained red, and the nuclei of the nerve-cells will also appear red. 14. Golgi's Methods. — These methods have yielded most excel- lent results in the study of the central nervous system, the dis- tribution of the peripheral nerves, and the delicate terminations of the ducts of glands ; e. g., the bile-capillaries. The methods must be regarded as special procedures in such studies, and can but be referred to here. They all depend upon hardening in some chromium salt, with or without the addition of osmic acid, and the subsequent impregnation with silver nitrate. A precipitate is thus produced on or within certain of the elements in the specimen, giving them a dark-brown or black color. The methods are capricious, and not all of the tissue-elements of like character in the specimen are rendered prominent. This is an advantage, but necessitates a degree of care in the interpretation of the results. Furthermore, irrelevant precipitates may form in the tissues which have no definite relations to any structure. Considerable practice is, there- fore, required for the successful employment of all these methods, not only for a satisfactory execution of the manipulations, but also in the study of the results. The methods have no value for the study of cell-structure, since the whole cell is either covered or filled with the precipitates formed during the impregnation with silver. Golgi has divided his methods into three groups : the slow, the rapid, and the mixed. For the details of these methods and of the various modifications introduced by different investigators the student is referred to the journals on microscopy. It must suffice to state here that the slow method begins with a hardening of the tissues in a 2 per cent, solution of potassium bichromate, which is gradually raised to 5 per cent. This hardening takes from fifteen days to three months. In the rapid method the tissues are first hardened in a mixture of 4 parts of a 2 per cent, solution of potas- sium bichromate and 1 part of a 1 per cent, solution of osmic acid. The tissues remain in this mixture for from two to six days, when they are ready for impregnation. For either method the pieces of tissue should not be thicker than 1.5 cm. 428 HISTOLOGICAL TECHNIQUE. Methods of Dehydration. The final manipulation in nearly all the methods for staining described above is a washing of the sections in water. This water must be removed before permanent mounts can be made. Dehy- dration is accomplished by treating the sections with alcohol. If they are impregnated, or have been embedded in collodion or cel- loidin, they must not be dehydrated in absolute alcohol, as that dis- solves the collodion. In such cases 95 per cent, alcohol is employed, the sections being treated with two baths of alcohol. When sections have been stained with carmine a contrast-stain may be obtained by adding a few small crystals of picric acid to the first dish of dehy- drating alcohol. The excess of picric acid is then removed by the alcohol in the second dish. Absolute alcohol may be used for dehy- dration when the sections have not been embedded in collodion or celloidin. When anilin-dyes have been used to stain sections it must be borne in mind that alcohol not merely dehydrates, but also differ- entiates the stain. If the sections are left too long in the alcohol, they may lose more color than is desired. Sections that are to be mounted in glycerin or glycerin-jelly require no dehydration, but can be mounted directly from water. Methods of Clearing. Clearing is necessary when specimens are to be permanently mounted in Canada balsam or dammar. Its object is to impreg- nate the section with some liquid that will drive out alcohol and also be miscible with the resin used for mounting. Of these clear- ing-agents there is a large number, from which a choice must be made according to the method of embedding that has been employed and the nature of the dye with which the tissues have been stained. Clearing-agents also differ in their miseibility with water, some requiring dehydration with absolute alcohol, others clearing well when 95 per cent, alcohol has been used for dehydration. 1. Xylol. — This is an excellent clearing-agent when the sections have been well dehydrated with absolute alcohol. It does not injure anilin-dyes. It is, perhaps, the best clearing-agent for sections of tissue stained with borax-carmine before cutting', when no counter-stain is employed. Xylol then both removes the paraffin in the section and clears it. METHODS OF MOUNTING. 429 2. Carbol-xylol. — Carbolic acid crystals (melted), 1 vol. Xylol, 3 vols. This mixture is much more tolerant of water than pure xylol. Sections dehydrated in 95 per cent, alcohol may be cleared Avith this reagent, which does not dissolve collodion. The carbolic acid used should be pure, but need not be the more expensive synthetic product. 3. Oil of Bergamot. — This light-green essential oil clears well and does not dissolve collodion. It may be used when 95 per cent, alcohol has been employed for dehydrating. 4. Oil of Origanum. — The oleum origani cretici should be used. It is of light-brown color and clears sections dehydrated in 95 per cent, alcohol or stronger. It slowly discharges anilin-colors. 5. Oil of Cloves. — This clearing-agent dissolves collodion and discharges anilin-colors. It may be used when it is desired to get rid of the collodion used for embedding after the sections have been stained. This removal is favored by dehydration in absolute alcohol before clearing. 6. Oil of Cedar-wood. — This, when pure, has a very light-yellow color and smells like cedar-wood. It should be free from the more pungent odor of the oil derived from the leaves. This essential oil does not discharge anilin-colors, and is, therefore, useful when those dyes have been employed. It clears slowly, but well, and may be used after dehydration with 95 per cent, alcohol. Methods of Mounting. Sections that have been treated by the foregoing methods of preparation are fitted for mounting in a solution of some resin. The most commonly employed are Canada balsam and dammar. The best solvent for these resins is xylol, though chloroform and benzol are sometimes used for this purpose. All traces of turpen- tine should be removed from the balsam before its solution, to avoid the discharge of stains with haematoxylin or anilin-dyes which tur- pentine occasions. "When sections are transferred from alcohol to a clearing-agent they float upon the surface of the latter, and can then be flattened and all folds removed. As the alcohol is extracted the sections 430 HISTOLOGICAL TECHNIQUE. sink in the clearing-agent. In order to transfer them from the clearing-agent to a slide, the first step in mounting, a good method is to slip a strip of cigarette-paper under the section, withdraw it along with the section (using a platinum needle as aid, if necessary), drain off the superfluous fluid, and then lay the cigarette-paper on the slide, section side down. Light pressure will now squeeze out considerable of the clearing-agent, when the paper can be stripped from the section and slide, leaving the section nearly dry and with- out folds or wrinkles. With a little care, this method of transferring the section to the slide rarely fails. When such is the case the manipulations must be repeated. A drop of the mounting-medium is now placed upon the section and a cover-glass laid on and gently pressed down until it comes in contact with the section and the excess of balsam or dammar is expelled from beneath the cover. If the sections tend to raise the cover, the latter may be weighted with a bullet placed in its centre. Freshly mounted specimens are not so favorable for examination with high powers as those that have been mounted for a few hours or days. This is because the refractive indices of the clearing-agent and mounting-medium are not identical. When these have become thoroughly mixed, or the former has evaporated, the specimen is impregnated with and surrounded by a homogeneous medium that does not scatter the light passing through it. Canada balsam has a somewhat higher refractive index than dammar. It therefore renders the sections a little more transparent and more completely obliterates the structure-picture. When it is desired to retain as much of the structure-picture as possible, which is usually the case, dammar should be chosen for the mount- ing-medium. It dries a little more slowly than balsam, but soon is sufficiently dry at the edges of the cover-glass to preserve the sec- tion from injury. If the slides are kept in a horizontal position, in a warm place (40° to 50° C. ; 104° to 122° F.), for a couple of days, they will be dry enough for storage, but for several weeks must be handled with care. Stained sections may be examined in glycerin, having been mounted by the same manipulations as those used for mounting in balsam, without previous dehydration or clearing. Such mounts are, however, difficult of preservation. The various cements that have been recommended for fastening the edges of the cover-glass to the slide are usually inefficient, as the changes of temperature RAPID PREPARATION OF SECTIONS FOR DIAGNOSIS. 431 that are inevitable cause the glycerin to make its way between the glass and cement, loosening the latter. A better medium than glycerin for sections that cannot be sub- jected to the action of alcohol for the purpose of dehydration is glycerin-jelly. This is prepai'ed by soaking the best French gelatin in cold water until it has imbibed all it will readily take up, then melting the gelatin, after pouring off the excess of water, and adding an equal bulk of glycerin. A little carbolic acid may be added to the mixture to preserve it. The manipulations for mount- ing are similar to those given above, the sections being transferred from water to the slide. The glycerin-jelly may be melted and a drop placed upon the section, or a little lump of the solid jelly may be placed upon a cover-glass, melted by gentle heat, and the cover- glass then inverted over the section on the slide. After the jelly has dried at the edges of the cover-glass they may be painted with xylol balsam, dammar, or some cement. The Rapid Preparation of Sections for Diagnosis. The most expeditious means of obtaining sections of fresh tis- sues is to cut them without preliminary treatment with reagents, either free hand with a razor, or with the aid of a freezing mi- crotome (page 415). Such sections may be stained with methylene- blue (aqueous solution, page 423), or they may be examined in neutral salt solution. If they are to be stained, spread them out on a slide, pour a few drops of the methylene-blue solution over them, and, after a few moments, wash off the dye with water and cover the section. If such rapid work is not necessary, the sections can be fixed in formalin (page 416), and, after washing out that reagent, stained. Such sections may be hardened and dehydrated, by placing them in dishes of increasingly strong alcohols, and finally mounted in dammar ; but the results are by no means so good as when fixation and hardening are done before sections are cut. When time is not pressing the following method will give good results : 1. Fix and harden pieces not over 1 inch thick in absolute alcohol on quick-lime over night (page 407). 2. Dip the specimen in thick collodion and embed it on a glass block by the rapid method (page 412). When the block has been in 80 per cent, alcohol for three or four hours it may be cut ; but it is better to let the collodion harden for twenty-four hours. 432 HISTOLOGICAL TECHNIQUE. 3. Stain with hematoxylin and eosin (page 418), cutting short the time of washing after the hsematoxylin, if in a hurry. 4. Dehydrate in 95 per cent, alcohol ; two successive baths. 5. Clear in carbol-xylol. 6. Mount in xylol-dammar. Very serviceable sections can be prepared in less than twenty- four hours by this method, and the specimens, though not of the best quality, will be permanent, and may be kept for future refer- ence. Special Methods. The foregoing methods are for the preparation of tissues from which sections must be made before they are fit for examination under the microscope. The physician is, however, frequently called upon to examine other objects, when the following directions will be found useful. 1. Examination of Urinary and other Sediments. — For the collec- tion of the sediment vessels with vertical walls should be used, not conical glasses. A test-tube answers very well. The sediment should be allowed to settle for several hours in a cool place, to avoid decomposition ; or, better, the sediment should be precipitated by means of a centrifuge. It should be borne in mind that urine becomes alkaline during decomposition, and that the ammonia pro- duced causes changes in the characters of the crystalline or other inorganic constituents of the sediment, and also renders the identi- fication of the organic constituents difficult or impossible. When the sediment has collected at the bottom of the vessel a portion should be removed with a pipette for examination. Place the finger over one end of the pipette before introducing it into the liquid, to retain the air, then place the other end in contact with the sediment and allow the air to escape slowly by raising or moving the finger a little. Close the upper end of the pipette and withdraw it. Now carefully wipe the outside of the pipette and let the fluid escape until a good sample of the sediment is at the end of the tube. Place a drop of this sediment on a slide and cover. Ex- amine the specimen with a low power at first, taking care to use a very small diaphragm. In this way the presence of urinary casts may be more rapidly determined than if a high power is used. When there is doubt as to a given object being a cast examine it with a higher power. After the specimen has been examined for casts and other objects large enough to be identified with a low power, SPECIAL METHODS. 433 use the high power for the detection of red blood-corpuscles, pus, etc. Objects in urinary sediments may be stained with aqueous methylene- blue, Gram's solution of iodine, or alum-carmine ; or their chemical nature determined by means of microchemical reac- tions. 2. Preparation of Cover-glass Smears. — These are used for the examination of blood, pus, sputa, cultures of bacteria, etc., when it is desired to employ stains. They are also employed occasionally for the study of some of the constituents of soft tissues. A small drop, or fragment, of the specimen is placed between two cover-glasses. If the specimen is sufficiently fluid, it will at once spread out into a thin layer between the covers. When this is not the case pressure may be used. The covers are then drawn apart, not lifted, leaving a coating upon both. They are allowed to dry spontaneously, after which the film is fixed by passing the cover-glasses three times through a flame, care being taken not to scorch the film, which should not come in contact with the flame. Heat applied through the glass to the dry film will render it insol- uble and affix it to the cover. The constituents of the film may then be stained on the cover-glass, the latter being either floated on the dye or immersed in it as though it were a section. Hema- toxylin and eosin may be employed ; but anilin-dyes, such as meth- ylene-blue, carbol-fuchsin, anilin-gentian- violet, etc., are more com- monly used. 3. Examination of Sputa for Tubercle Bacilli. — The small cheesy particles in the sputa are most likely to contain tubercle bacilli. Cover-glass smears are stained by the following method : a. Stain fifteen minutes in freshly filtered carbol-fuchsin at the room-temperature, or heat until vapors rise from the surface of the dye, and maintain that temperature for about three minutes. b. Wash off the excess of dye with water. c. Differentiate in dilute sulphuric acid, prepared by adding 5 cc. of pure acid to 95 cc. of distilled water, until the cover-glass has only a faint tinge of pink when the acid is washed off with water. d. Wash in water to remove the acid. e. Counterstain with aqueous methylene-blue for two minutes. /. Wash in water. g. Dry the cover-glass and mount it, film side down, on a drop of xylol-dammar. The tubercle bacilli will be stained red, while other bacteria and 28 434 HISTOLOGICAL TECHNIQUE. the nuclei of cells will be blue. This method, like all others used for the detection of the tubercle bacillus, depends upon the fact that that bacillus takes up colors with reluctance, but, after staining, holds them tenaciously. The specimen is therefore first stained with a strong dye, is then decolorized with some agent that will discharge the color from all bacteria except the tubercle bacillus (and spores, which, however, have a different shape from that of the tubercle bacillus), and afterward stained with a weaker dye of another color which is imparted to the bacteria that have been decolorized. 4. Examination of Urethral Pus for the Gonococcus. — The gono- coccus is shaped a little like a coffee-bean, and usually occurs in pairs with the flattened surfaces of the individual cocci facing each other. In pus it is frequently situated within the leucocytes, while the other varieties of pyogenic cocci usually lie outside of the pus- corpuscles. The gonococcus is decolorized by treatment with Gram's iodin solution followed by alcohol; the more common cocci found in suppuration are not decolorized. These differences in shape, sit- uation, and behavior toward dyes serve to distinguish the gonococci from the other cocci that may be present. The smears, fixed by heat, are stained as follows : a. Stain for five minutes in freshly filtered anilin-gentian-violet. b. Wash off excess of dye with water. c. Immerse in Gram's solution for two minutes. <1. Decolorize in 95 per cent, alcohol till no more color is given off. c. Stain two minutes in aqueous fuchsin, prepared in a manner similar to that used for aqueous methylene-blue. Bismarck-brown may be used for this eounterstain in place of the fuchsin. /'. Wash in water, dry, and mount in dammar or balsam. The gonococci will be stained by the second dye used; other cocci be- longing to the pyogenic group will be a dark purple, they having retained the color first imparted to all the bacteria by the gentian- violet. In this case the gonococci are distinguished from the other cocci by taking advantage of the fact that they are " negative to Gi'am," while the others are " positive." 5. Examination of Blood-smears. — Hematoxylin, followed by a strong eounterstain with eosin, will furnish useful specimens for most purposes. The differentiation of the various granules in the white corpuscles described by Ehrlieh requires special methods, for a description of which the reader is referred to special works on the SPECIAL METHODS. 435 blood or clinical microscopy. The malarial plasmodia are best detected in perfectly fresh blood, examined immediately with an immersion-lens, when their changes of form serve to make them more easily recognizable than when they are sought in smears. In the latter they may be stained by the following method : a. Fix the film by means of heat, or, better, by immersion in absolute alcohol for half an hour. (In the latter case wash off the alcohol with water before staining.) b. Stain for several hours in Chenzinsky-Pehn's stain : Concentrated alcoholic solution of methylene-blue, 10 cc. 0.5 per cent, solution of eosin in 70 per cent, alcohol, 5 cc. Distilled water, 10 cc. The solution should be filtered before, and preserved from evap- oration during, the staining. c. Wash in water, dry, mount in xylol-dammar. The malarial plasmodia will be stained blue, the body of the red corpuscles red, the nuclei of the leucocytes blue, and eosinophile granules, within those cells, red. 6. Examination of Bacteria in Cover-glass Preparations. — If the bac- teria are already in a fluid, a drop is placed upon a cover-glass, spread over its surface, allowed to dry spontaneously, and then fixed by heat, as described above. If cultures on solid media are to be examined, a drop of water is first placed upon the cover-glass, and a little mass of the bacteria disseminated through it, and then the mixture is spread in a thin layer by means of the platinum needle. It is then dried and fixed, as in the preceding case. Such preparations may be stained with methylene-blue, carbol-fuchsin, by Gram's method (anilin-gentian- violet, followed by Gram's iodine solution, and then alcohol), or with some other anilin-dye. For the diph- theria or typhoid bacillus an alkaline methylene-blue (see Unna's formula) serves well. 7. Examination in Hanging Drop. — This method is useful for the observation of objects suspended in a fluid. It is extensively used in bacteriology for the study of living bacteria. A drop of the fluid is placed on the centre of a cover-glass, which is then inverted over the concavity in a hollowed slide. The edges of the cover- glass should then be sealed with a drop of water or oil, to prevent evaporation of the hanging drop. 436 HISTOLOGICAL TECHNIQUE. 8. Microchemical Reactions. — These reactions are resorted to to determine the chemical nature of objects under the microscope. Every stain is the result of a microchemical reaction, but as yet the knowledge obtained by staining tissues cannot always be ex- pressed in chemical language. The manipulations are usually so conducted that the reaction can be directly observed under the microscope. The object to be studied is placed in the middle of the field. The reagent used is then placed at one edge of the cover-glass, whence some of it will flow beneath the latter. To facilitate the entrance of the reagent a nar- row strip of filter-paper may be brought in contact with the oppo- site edge of the cover, withdrawing some of the fluid from beneath it. It is best to sharpen the end of the strip which comes in con- tact with the cover-glass, so that the absorption of fluid shall be slow ; otherwise the currents induced will be likely to wash the object from the field of vision. The following tests, applied in this way, may be of use : a. Urates. Insoluble in 1 per cent, acetic acid ; soluble, on the application of heat, in water (or urine). The slide must be removed from the microscope when heat is applied to it. b. Earthy phosphates. Dissolve on the addition of 1 per cent, acetic acid. Are not dissolved by heat. c. Calcium oxalate. Insoluble in 1 per cent, acetic acid ; soluble in 1 per cent, hydrochloric acid. d. Carbonates. Soluble in 1 per cent, acetic acid or hydrochloric acid, with evolution of gas-bubbles. e. Albuminoid granules. Become indistinct, and finally invisible, on the addition of 1 per cent, acetic acid or 1 per cent, potassium hydrate ; not blackened by osmic acid. /. Fatty granules. Not affected by 1 per cent, acetic acid or 1 per cent, potassium hydrate. Stained black or dark brown by osmic acid. g. Starch. Stained dark blue to black by iodine solutions. Use Gram's solution. h. Cellulose. Stained yellow by iodine solutions. If the water be then removed and concentrated sulphuric acid introduced, the color becomes blue. The walls of most vegetable cells are composed of cellulose. /. Teichmann's test for hemoglobin. This test depends upon the conversion of the haemoglobin or its derivatives into hsemin, which SPECIAL METHODS. 437 crystallizes in rhombic plates of a reddish-brown color. The haemin is produced by heating with a little salt and strong acetic acid. Evaporate a drop of neutral salt solution to dryness on a slide. Place the substance to be tested upon it and cover. Fill the space between cover and slide with glacial acetic acid and heat over a flame till bubbles begin to form. Maintain that heat for a few minutes, replacing loss by fresh additions of acetic acid. Let the slide cool slowly, and, when cold, examine. If the results are nega- tive, repeat the heating with acetic acid. The acid should not . actually boil, but should be kept at the point of incipient ebullition. j. Tests for amyloid substance. Sections of fresh tissue may be soaked for some time in Gram's solution, then washed and examined in water. Amyloid substance is stained reddish-brown, the tissues yellow. Sections of tissues fixed in alcohol, corrosive sublimate, or formaldehyde, may be stained in a solution of 1 per cent, methyl- violet dissolved in distilled water, without the addition of alcohol. The sections are then washed in 1 per cent, hydrochloric acid for the purpose of differentiating the stain. After thorough washing in several changes of water they may be mounted in glycerin-jelly. The amyloid substance is stained reddish-violet, the other tissues blue. k. Test for iron in pigmentations. The iron from the haemo- globin of the blood is sometimes present in the pigmentation result- ing from old extravasations, in the form of hsemosiderin. The same compound is also sometimes found in the tissues in cases of pernicious anaemia. The presence of iron in this pigmentation may be demonstrated by the following method : (a) The tissues should be fixed in alcohol. (b) Soak the section in a 2 per cent, solution of potassium ferro- cyanide for ten minutes. (c) Transfer to Orth's acid alcohol (page 422) for five or ten minutes. The sections may now be examined in a glycerin-mount with a wide diaphragm, or they may be counterstained, for which purpose treat as follows : (V/) Wash with water. (e) Stain with Orth's lithio-carmine. (/) Dehydrate and mount in xylol-dammar. The iron in the section is converted into Prussian blue ; the nuclei of the cells, when the counterstain has been employed, are red. 438 HISTOLOGICAL TECHNIQUE. I. Examination of sputa for elastic fibres. In pulmonary disease involving a destruction of pulmonary tissue and the appearance of fragments in the expectoration, elastic fibres from the alveolar walls may frequently be found in the sputa : Fill a test-tube one-third full of sputa, add five or six drops of 36 per cent, potassium hydrate solution, and boil the mixture for three or four minutes. Add an equal bulk of distilled water. Divide the contents of the tube between the two tubes of the cen- trifuge and precipitate their contents. If elastic fibres were pres- ent, they will be found either in the sediment or in the scum on the top of the fluid. 9. Methods of Maceration. — a. One-third alcohol. 95 per cent, alcohol, 35 cc. Distilled water, 65 " This dilute alcohol is excellent for the separation of epithelium from the surfaces of mucous membranes. The fresh tissues are placed in the alcohol for a day or two, after which the cells can easily be detached and separated by shaking. The cells are well preserved, and may be stained with methylene-blue or alum-car- mine. b. Potassium hydrate. Potassium hydrate, pure by alcohol, 36 grams. Distilled water, 64 cc. The solution should be cold before use. It cannot be filtered through paper ; but if not clear, should be decanted from any sedi- ment, or a fresh solution prepared. Maceration takes place very quickly in this solution. The tissues can usually be teased apart within fifteen to thirty minutes. They must be examined in the potash solution without dilution, as the addition of water quickly destroys the tissue-elements. For this reason the specimens to be macerated should be placed in several times their bulk of the pot- ash solution ; otherwise the water they contain will dilute the pot- ash. Permanent mounts cannot be made. c. Chromic acid. A solution of 1 part of the acid in 10,000 parts of distilled water will facilitate the teasing apart of tissue- elements which have macerated in it for one to several days. After careful washing on the slide alum-carmine alone, or followed by picric acid, may be used for staining. SPECIAL METHODS. 439 10. Methods of Decalcification. — Tissues which contain calcified nodules or bone must be freed from lime-salts before they can be cut. It is difficult to do this rapidly without injury to the softer tissue-elements. When good results are desired, and the necessary time can be afforded, the tissues should first be fixed and hardened, small pieces being selected. Zenker's fluid fixes well for this pur- pose, but Orth's fluid or alcohol may be used. If Zenker's or Orth's fluid is used, the tissues must be washed in water and hardened in alcohol for at least a day before they are decalcified (see Methods of Fixing and Hardening, pp. 403, 408). Decalcification is accomplished by treatment with acids. Five per cent, nitric acid will decalcify small pieces of bone in from one to five days. The progress of the decalcification may be deter- mined by pricking the tissue with a needle, but after it appears to be soft it is well to continue the action of the acid for a day or two, lest some undissolved particles should remain and injure the edge of the microtome-knife. A saturated aqueous solution of picric acid is sometimes used for decalcifying. Its action is very slow, though not injurious to the tissues, which require no prelimi- nary treatment, the picric acid acting as a fixing and decalcifying agent. After decalcifying in nitric acid the tissues should be thoroughly washed in running water for twenty-four hours and then rehardened in alcohol, after which they may be embedded. After decalcifying in picric acid the tissues are placed in 70 per cent, alcohol and hard- ened without previous washing in water. When rapid decalcification is necessary nitric acid and phloro- glucin, which restrains the destructive action of the acid, may be used. The solution is prepared by dissolving 1 gram of phloro- glucin in 10 cc. of pure nitric acid. To this 100 cc. of 10 per cent, nitric acid are added. Decalcification takes place within a few hours in this solution, which contains about 20 per cent, of nitric acid. The tissues should then be washed and hardened. Another rapid method which combines decalcification with hard- ening is to place the fresh tissues in a large bulk of 5 per cent. nitric acid in 80 per cent, alcohol. After decalcification has taken place the tissues are hardened in alcohols of increasing strength, large quantities being used in order to remove the acid. Before staining, the sections should be washed thoroughly in water to get rid of any residual traces of acid. INDEX. t BSCESS, 312 A cold, 319 Absorption, 295 Achromatin, 34 Acidophilic cells, 119 Active hyperemia, 298 Acute inflammation, 297 parenchymatous inflammation, 268 nephritis, 272 Adeno-carcinoma, 390 Adeno-fibroma, 377 Adenoma, 376 Adipose tissue, 78 Adrenal bodies, 186 Adventitia, 112 Akromegaly, 191 Albumin, Mayer's, 417 Albuminoid degeneration, 266 Alcohol, absolute, 407 Alveoli, pulmonary, 171 Amoeba, 28 Amyloid infiltration, 281 substance, tests for, 437 Anaemic infarcts, 332 Angiomata, 373 Angiomatous tumors, 373 Anilin-water, 424 Areolar tissue, 76 Arteries, 110 helicine, 223 Association-fibres of cerebrum, 249 of spinal cord, 239 Atrophy, 284 functional, 284 pressure-, 285 senile, 287 Attraction-spheres, 35 Axis-cylinder, 97 BACTERIA, examination of, 435 Basement-membrane, 58 Basophilic leucocytes, 126 Bergamot, oil of, 429 Bladder, 164 Blood, 122 -plates, 126 -smears, preparation of, 434 Bodies, adrenal, 186 Malpighian, 154 Bodies, Malpighian, of spleen, 177 Pacinian, 252 pearl-, 390 polar, 35, 217 Body, pituitary, 139 Bone, 68 canaliculi of, 68 general character of, 68 Haversian canals of, 68 lacuna? of, 68 -marrow, 71, 119 red, 119 yellow, 119 regeneration of, 338 Bowman, glands of, 255 Bowman's capsule, 159 Bronchi, 169 Bronchioles, 170 Broncho-pneumonia, 317 Brownian movement, 29 Brunner, glands of, 141 Bulb, olfactory, 258 glomeruli of, 257 CACHEXIA strumipriva, 183 Calcareous infiltration, 282 Calcium oxalate, tests for, 436 Callus, 309 Canada-balsam, 428, 430 Capillaries, 113 Capsule, Bowman's, 159 Glisson's, 146 Capsules, supra-renal, 186 Carbol-fuchsin, 423 Carbonates, tests for, 436 C'arbo-xylol, 429 Carcinoma, 382 colloid, 388 medullary, 384 scirrhous, 384 simple, 384 Cardiac glands, 136 muscles, 89 Carmine, alum-, 421 borax-, 421 lithio-, 422 neutral, 420 Carotid glands, 194 Cartilage, 64 441 442 INDEX. Cartilage, elastic, 67 flbro-, 66 general character of, 64 hyaline, 66 matrix of, 65 ossification of, 64 regeneration of, 338 Catarrhal inflammations, 316 pneumonia, 317 Cedar-wood, oil of, 429 Cell, or cells, 27 acidophilic, 119 compound granule-, 316 decidual, 215 of Deiters, 260 -division, 40 amitotic, 40 centrosome in, 34 ganglion-, 95 giant-, 40, 119 glia-, 101 goblet-, 52, 139 hair-, 260 migratory, 124 mitral, 258 of Muller, 262 nerve-, 95 organs of, 31 plasma-, 120 prickle-, 55 of Purkinje, 243 reproduction of, 34 of .Sertoli, 225 stellate, 245 sustentacular, of retina, 261 in testis, 227 wandering, 124 Cellulose, tests for, 436 Centrosome, 31 Cerebellum, 243 Cerebrum, 246 association-fibres of, 250 commissure-fibres of, 249 projection-fibres of, 249 Cheesy degeneration, 274 Chemotactic substances, 309 Chemotaxis, 309 Chondroma, 350 Chromatin, 34 reduction of, 226 Chromolysis, 294 Chromoplasm, 34 Chromosomes, 37 Chronic inflammations, 322 interstitial, 324 parenchymatous, 269 Chyle, 126 Cicatricial tissue, 308 Ciliated epithelium, 53 Circulatory system, 108 Cirrhosis of liver, 323 Clarke, column of, 241 Clearing, methods of, 428 Clearing, methods of, bergamot, oil of, 429 carbol-xylol, 429 cedar-wood, oil of, 429 cloves, oil of, 429 origanum, oil of, 429 xylol, 428 Clefts of Lantermann, 99 Cloves, oil of, 429 Coagulation, explanation of, 127 -necrosis, 294 Coccygeal gland, 195 Collateral fibres of spinal cord, 239 Colliquative necrosis, 295 Collodion, 409, 412 Colloid, 181 carcinoma, 388 degeneration, 278 Colon, 142 Colostrum, 219 -corpuscles, 219 Column of Clarke, 241 Columnar epithelium, 52 Commissure-fibres of cerebrum, 249 Compensatory hypertrophy, 289 Congestion, passive, 326 Connective tissue, 63 tumors, 347 Contractile substance, 83 Cord, spinal, 236 Corium, 196 Corpora amylacea, 224 Corpus album, 210 cavernosum, 222 hsemorrhagicum, 210 luteum, 210 spongiosum, 222 Corpuscles, colostrum-, 219 genital, 253 of Krause, 253 of Meissner, 253 red, 123 tactile, 252 white, 124 Croupous inflammation, 317 membrane, 319 Crypts of Lieberkiihn, 139 Cubical epithelium, 49 Cuticle of epithelium, 50 Cuticularized epithelium, 54 Cutting, methods of, 415 free-hand, 415 frozen sections, 415 celloidin sections, 416 collodion sections, 416 Cylindroma, 356 Cystoma, 392 Cytoplasm, 29, 32 DECALCIFICATION, methods of, 439 Decidual cells, 215 Degenerations, 265 albuminoid, 266 cheesy, 274 INDEX. 443 Degenerations, colloid, 278 fatty, 266 hyaline, 280 keratoid, 280 mucous, 277 of nerves, 283 parenchymatous, 266 Dehydration, methods of, 428 Deiters' cells, 260 Dendrite, 234 Dermoid cysts, 392 Developmental hypertrophy, 230 Diapedesis, 301 Diaster-phase of karyokinesis, 38 Digestive organs, 128 Diphtheritic inflammation, 318 membrane, 294 Discus proligerus, 209 Dispirem-phase of karyokinesis, 38 Ductless glands, 62, 180 Duodenum, 137 ECTODERM, 20 Ectoplasm, 29 Elastic cartilage, 67 fibres, 73 Eleidiu, 198 Elements, sarcous, 93 Elementary tissues, 41 Embedding, methods of, 411 celloidin, 412 collodion, 412 paraffin, 413 Embolism, 330 Embryonic layers, 22 Encapsulation, 296 Endoderm, 20 Endoneurium, 100 Eudoplasm, 29 Endothelioma, 355 Endothelium, 45 functions of, 48 general characters of, 45 regeneration of, 336 Energy, kinetic, 18 potential, 18 Eosin, 420 Eosinophilic leucocytes, 126 Epicardium, 109 Epidermis, 197 Epididymis, 225 Epiglottis, 168 Epineurium, 100 Epithelial tumors, 376 Epithelioma, 391 Epithelium, 49 ciliated, 53 columnar, 52 cubical, 49 cuticle of, 50 cuticularized, 54 functions of, 41, 57 activities of, 57 Epithelium, general characters of, 49 germinal, 207 glandular, 50 pavement-, 51 regeneration of, 336 stratified, 54 transitional, 56 Erectile tissue, 222 Erythroblasts, 119 External genitals, 217 Exudate, inflammatory, 301 FALLOPIAN tubes, 210 Fatty degeneration, 266 infiltration, 574 Fibres, association-, of cerebrum, 250 of cord, 239 collateral, of cord, 239 commissure-, of cerebrum, 249 connective-tissue, staining, 425 elastic, 73 moss-, 246 nerve-, 96 staining, 426 projection-, of cerebrum, 249 Sharpey's, 70 white, 73 yellow, 73 Fibrin, 126 Fibrinous inflammation, 313 Fibro-cartilage, 66 Fibroma, 347 Fibrous tissues, general character of, 72 regeneration of, 336 Figures, mitotic, preservation of, 406 Fixation, methods of, 403 alcohol, absolute, 407 boiling, 408 Flemming's solution, 406 formaldehyde, 405 mercuric chloride solution, 405 Miiller's fluid, 403 Orth's fluid, 404 Zenker's fluid, 404 Flemming's solution, 406 Follicles, Graafian, 207 lymph-, 143 Formaldehyde, 405 Fractures, healing of, 308 Functional atrophy, 284 hypertrophy, 288 GALL-BLADDER, 151 Ganglion-cells, 95, 234 Gangrene, 296 dry, 296 moist, 296 Genital corpuscles, 253 Gentian-violet, 423 Germinal epithelium of ovary, 207 Giant-cell sarcoma, 367 Giant-cells, 40, 119 Gianuzzi, crescents of, 131 444 INDEX. Gland, mammary, 218 thyroid, 181 Glands of Bowman, 255 of JBrunner, 141 cardiac, of stomach, 136 carotid, 194 coccygeal, 195 ductless, 62, 180 lymphatic, 114 parotid, 131 pyloric, 136 salivary, 131 sebaceous, 201 secreting, 58 sublingual, 131 submaxillary, 131 sweat-, 198 Glandular epithelium, 50 Glioma, 394 Glisson's capsule, 146 Glomeruli, olfactory, 258 Glomerulus, 158 Glycerin, 430 jelly, 431 Glycogenic infiltration, 275 Goblet-cells, 52, 139 Gonococcus, staining of the, 434 Graafian follicles, 207 development of, 208 Gram's solution, 424 Granulation-tissue, 304 Granules, albuminoid, tests for, 436 fatty, tests for, 436 Granulomata, 318 HEMANGIOMA, 374 Haematoidin, 328 Hematoxylin, 418 Haemoglobin, tests for, 436 Haemorrhage, 328 Haemosiderin, 328 Hair, 199 -cells, 260 cuticle of, 200 -follicles, 199 development of, 204 Planging-drop preparations, 435 Hardening, methods of, 408 Haversian canals, 68 Hearing, 259 Heart, 109 Helicine arteries, 223 Henle, tubes of, 155 Hepatization of lung, gray, 313 red, 313 Hyaline cartilage, 66 degeneration, 280 Hyaloplasm, 29 Hyperemia, active, 298 inflammatory, 298 passive, 286, 326 Hyperplasia, 288 inflammatory, 290 Hypertrophy, 288 compensatory, 289 developmental, 290 functional, 288 inflammatory, 290 Hypophysis cerebri, 189 IMPBEGNATION, methods of, 409 celloidin, 409 collodion, 409 paraffin, 409 Infarcts, 332 anaemic, 332 haemorrhagic, 332 Infiltration, amyloid, 281 calcareous, 282 fatty, 274 glycogenic, 275 serous, 276 Infiltrations, 265 Inflammation, acute, 297 parenchymatous, 268 catarrhal, 316 chronic, 322 interstitial, 324 parenchymatous, 269 croupous, 317 diphtheritic, 318 fibrinous, 313 serous, 315 Inflammatory exudate, 301 hyperemia, 298 hyperplasia, 290 hypertrophy, 290 repair, 303 stasis, 298 Infundibula of lung, 171 Interstitium, 106 Intestine, small, 141 Intima, 110 Involuntary muscles, 88, 91 Iron-hematoxylin stain, 425 tests for, 437 KARYOKINESIS, 34 diaster-phase, 38 dispirem-phase, 38 monaster-phase, 37 significance of, 39 spirem-phase, 35 Karvolvsis, 294 Keloid," 360 Keratin, 198 Keratoid degeneration, 280 Kidney, cortex of, 153 pelvis of, 163 Malpighian bodies of, 154 Kidneys, 153 Kinetic energy, 18 Krause, corpuscles of, 253 T ACTEA.LS, 114 1 1 Lantermann, clefts of, 99 INDEX. 445 Larynx, 168 Layers, embryonic, 22 Leiomyoma, 370 Leucocytes, 1*2-1 basophilic, 126 emigration of, 300 eosinophilic, 126 large mononuclear, 125 polynuclear neutrophilic, J 25 Lieberkuhn, crypts of, 139 Lipoma, 350 Liver, 146 cirrhosis of, 323 functions of, 151 lobules of, 147 Lobar pneumonia, 313 Lung, functions of, 173 gray hepatization of, 313 infundibula of, 171 red hepatization of, 313 Lymph, 122 -nodes, 114 Lymphadenoid tissue, 76 Lymphatic glands, 114 Lymphatics, 114 Lympho-angioma, 376 Lymphocytes, 125 Lympho-sarcoma, 363 MACERATION, methods of, 438 alcohol, 438 chromic acid, 438 potassium hydrate, 438 Malpighian bodies of kidney, 154 bodies of spleen, 177 Mammary gland, 218 Marrow, 71, 119 Matrix of cartilage, 65 Maturation of the ovum, 217 Mayer's albumin, 417 Measurements, microscopical, 398 Medullary carcinoma, 384 sheath, 97 Meissner, corpuscles of, 253 Melano-sarcoma, 369 Membrane, basement, 58 croupous, 318 diphtheritic, 294 pyogenic, 313 Mercuric chloride solution, 405 Mesoderm, 22 Metakinesis, 37 Metaplasia, 291 Metaplasm, 33 Methylene-blue, aqueous, 423 Unna's, 422 Microchemical reactions, 436 Microscope, care of, 397 selection of, 397 Microscopical measurements, 398 technique, 399 Migratory cells, 124 Mitral cells, 258 Monaster-phase of karyokinesis, 37 Mononuclear leucocytes, large, 125 Moss-fibres, 246 Motor plates, 104 Mounting, methods of, 429 Canada-balsam, 428, 430 Dammar, 428 glycerin, 430 glycerin-jelly, 431 Movement, Brownian, 29 amoeboid, 29 Mucoid marrow, 119 Mucous degeneration, 277 tissue, 74 Mucus, 278 Miiller, cells of, 262 Miiller's fluid, 403 Muscular tissues, 83 tumors, 370 Muscle, cardiac, 89 regeneration of, 340 involuntary, 88, 91 smooth, 83 function of, 88 regeneration of, 339 striated, 91 regeneration of, 340 Myelin, 97, 98 Myelocytes, 119 Myxcedema, 183 Myxoma, 353 NAILS, 201 Necrosis, 293 coagulation-, 294 liquefaction, 295 of nucleus, 294 Nephritis, acute parenchymatous, 272 Nerve-cells, 95 degeneration of, 2S3 -fibres, 96 -terminations, 103 Nervous system, 234 tissues, 94 regeneration of, 340 Neurilemma, 97 Neurite, 234 Neuroglia, 101 Neurons, 234 Nodes of Kanvier, 98 Nucleolus, 29, 33 Nucleus, 29 necrosis of, 294 structure of, 33 /TjISOPHAGUS, 134 \Jh Olfactory bulb, 258 layers of, 258 glomeruli, 258 Organs, 106 Orth's fluid, 404 Origanum, oil of, 429 Ossification of cartilage, 64 446 INDEX. Osteoma, 353 Ovary, 207 Ovula Nabothi, 216 Ovum, 20 maturation of, 217 PACINIAN bodies, 252 Pancreas, 142 Papilloma, 394 Paraffin, 409, 413 Parathyroids, 185 Parenchyma, 106 Parenchymatous degeneration, 266 inflammation, acute, 268 chronic, 269 nephritis, acute, 272 Passages, alveolar, 170 Passive congestion, 326 hyperemia, 326 Pavement-epithelium, 51 Pelvis, renal, 163 Penis, 222 Perichondrium, 65 Perineurium, 100 Periosteum, 71 Peyer's patches, 143 Phagocytosis, 332 Phosphates, earthy, tests for, 436 Pia mater, 251 Picture, color-, 402 structure-, 402 Pituitary body, 189 Plasma-cells, 120 Pleurisy, 314 Pneumonia, broncho-, 317 catarrhal, 317 lobar, 313 Polar bodies, 35, 217 Polynuclear neutrophilic leucocytes, 125 Potential energy, 18 Pressure-atrophy, 285 Prickle-cells, 55 Projection-fibres of cerebrum, 249 Prostate, 224 Protoplasm, 29 Psammoma, 356 Pseudopodium, 29 Pseudo-stomata, 47 Pulmonary alveoli, 171 Purkinje, cells of, 243 Pus, 312 Pyloric glands, 136 Pyogenic membrane, 313 I)ANVIER, nodes of, 98 \> Razor, stropping, 415 Reaction, microchemical, 436 Rectum, 142 Red corpuscles, 123 Regeneration of bone, 338 of cartilage, 338 of endothelium, 336 of epithelium, 336 Regeneration of fibrous tissue, 336 of muscles, cardiac, 340 smooth, 339 striated, 340 of nervous tissues, 340 of tissues, 334 Renal pelvis, 163 Repair, inflammatory, 303 Reproductive organs, 207 Respiratory organs, 168 Rete mucosum, 197 vasculosum, 233 Reticular tissue, 76 Retina, 260 sustentacular cells of, 261 Rhabdomyoma, 372 Round-cell sarcoma, large, 364 small, 362 SALIVARY glands, 131 Salt solution, normal, 399 Sarcolemma, 93 Sarcoma, 359 giant-cell, 367 large round-cell, 364 lympho-, 363 melanotic, 369 small round-cell, 362 spindle-cell, 365 Sarcoplasm, 93 Sarcostyles, 93 Sarcous elements, 93 Scar, 308 Schwann, sheath of, 98 Scirrhous carcinoma, 384 Sebaceous glands, 201 Secreting glands, 58 Secretion, internal, 62 Sections, rapid preparation of, 431 staining of, 402 Sediments, examination of, 432 Seminal vesicles, 225 Senile atrophy, 287 Serous infiltration, 276 inflammations, 315 Sertoli, cells of, 228 Sharpey's fibres, 70 Sheath of Schwann, 98 Sight, 260 Simple carcinoma, 384 Skin, 196 functions of, 203 Smears, cover-glass, 433, 435 Smell, 255 Smooth muscles, 83 Special senses, organs of, 252 Spermatids, 227 Spermatocytes, 227 Spermatogonia, 227 Spermatozoa, 231 Spinal cord, 236 association-fibres of, 239 collateral fibres of, 239 INDEX. 447 Spindle, achromatic, 37 Spindle-cell sarcoma, 365 Spirem, formation of, 35 Splrem-phase of karyokinesis, 35 Spleen, 176 Malpighian bodies of, 177 Spongioblasts, 262 SpoDgioplasm, 29 Sputa, elastic fibres in, 438 tubercle-bacilli in, 433 Staining, methods of, 418 carmine, alum-, 421 borax-, 421 lithio-, 421 neutral, 420 eosin, 420 fuchsin, carbol-, 423 gentian-violet, 423 Golgi's methods, 427 Gram' s solution, 424 hsematoxylin, 418 iron-haematoxylin, 425 methylene-blue, 422, 423 Pal's method, 426 Van Giesen's stain, 425 Stasis, inflammatory, 298 Starch, tests for, 436 Stellate cells, 245 large, 245 small, 245 Stomach, 134 Stomata, 46 pseudo-, 47 Stratum granulosum, 198 lucidium, 198 Stratified epithelium, 54 Striated muscles, 91 Stropping, method of, 415 Submaxillary glands, 131 Substance, contractile, 83 Suppuration, 296, 309 Supra-renal capsules, 186 Sustentacular cells of retiua, 261 of testis, 227 Sweat-glands, 198 TACTILE corpuscles, 252 Taste, 254 -buds, 254 Teasing, 400 Technique, microscopical, 399 Teeth, 205 Teledendrites, 234 Teleneurites, 234 Tendon, 80 Testes, 225 Tests for urates, 436 amyloid substance, 437 calcium oxalate, 436 carbonates, 436 cellulose, 436 granules, albuminoid, 436 fattv, 436 Tests for haemoglobin, 436 iron, 437 phosphates, earthy, 436 starch, 436 Tissue, adipose, 78 areolar, 76 cicatricial, 308 connective, 63 elementary, 41 recognition of, 43 erectile, 222 fibrous, 72 fixation of, 401 fixed elements of, 303 granulation-, 304 lymphadenoid, 76 mucous, 74 muscular, 83 necrosed, fate of, 295 nervous, 94 Tissues, cardiac muscular, 8! preparation of, 399 by cutting, 400 by maceration, 400 regeneration of, 334 reticular, 76 smooth muscular, 83 striated muscular, 91 Thrombo-phlebitis, 329 Thrombosis, 329 Thrombus, 329 Thymus, 192 Thyroid gland, 181 Thyro-iodine, 184 Tongue, 129 Tonsils, 143 Touch, 252 Trachea, 168 Transitional epithelium, 56 Tubercle, 320 -bacilli, detection of, 433 Tubercular ulcer, 322 Tuberculosis, 319 Tubes, Fallopian, 210 of Henle, 155 Tumors, 341 angiomatous, 373 hemangioma, 374 lymphangioma, 371 benign, 342 classification of, 345 connective-tissue, 347 chondroma, 350 cylindroma, 356 endothelioma, 355 fibroma, 347 keloid, 360 lipoma, 350 myxoma, 353 osteoma, 353 psammoma, 356 sarcoma, 359 giant-cell, 367 448 INDEX. Tumors, connective-tissue, sarcoma, large round-cell, 364 lympho-, 363 melanotic, 369 small round-cell, 362 spindle-cell, 365 epithelial, 376 adenoma, 376 adeno-fibroma, 377 cystic, 377 intracanalicular, 378 carcinoma, 382 adeno-carcinoma, 390 medullary, 384 simple, 384 scirrhous, 384 colloid, 388 cystoma, 392 epithelioma, 391 glioma, 394 etiology of, 342 malignant, 343 metastasis of, 344 mixed, 344 morbid changes in, 344 muscular, 370 leiomyoma, 370 rhabdomyoma, 372 nomenclature of, 345 papillomata, 394 Tunica albuginea, 226 vaginalis, 226 Tunica, granulosa, 209 media, 112 ULCER, tubercular, 322 Urates, tests for, 436 Ureter, 164 Urethra, 165 Urinary organs, 153 Uterus, 211 TTACUOLES, 30 V contractile, 30 Vagina, 216 Van Giesen's stain, 425 Vas deferens, 225 Vasa efferentia, 233 recta, 233 Veins, 113 Vesicles, seminal, 225 w ARTS, 395 White corpuscles, 124 fibres, 73 VYLOL, 428 yELLOW fibres, 73 ^ENKER'S fluid, 404 Catalogue of Backs PUBLISHED BY Lea Brothers & Company, 706, 708 & 710 Sansom St., Philadelphia. 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