COLUMBIA LIBRARIES OFFSITE HI Al III Mil firi S MAMI)AHn lilii liililll 111 ■HX64099202 QM551 .D92 Histology; normal an • •w*-*;^'' ■'"% ;'^'1'>".'!'V' ■'■ •*' <''»'' •''■'!•'. '^*^''.' ''* : ',:.) > :-V:>i:::- RECAP f «;:^-i; :;■:■;•;•'' *^ Columbia ?Hnibers(itp in tfje Citp of ^etD gorfe COLLEGE OF PHYSICIANS " ' AND SURGEONS jFrom ti)c ILibrarp of Br. CijriiEftian i^. I^crter 33onateti fap iHt£(. I^enrp B. Baktn 1920 HISTOLOGY: NORMAL AND MORBID. BY EDWARD K. DUNHAM, Ph.B., M.D., PROFESSOR OF GENERAL PATHOLOGY, BACTERIOLOGY, AND HYGIENE IN THE llNIVERSITY AND BELLEVUE HOSPITAL MEDICAL COLLEGE, NEW YORK. ILLUSTRATED WITH 363 ENGRAVINGS. LEA BROTHERS & CO., NEW YORK AND PHILADELPHIA. 1898. Entered according to Act of Congress in the year 1898, by LEA BROTHERS & CO., in the OflSce of the Librarian of Congress, at Washington. All rights reserved. ELEOTROTVPEO BV WESTCOTT fc THOMSON PHILAOA 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 deriveil 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 Jonnafire 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 purjjose 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- tolog-v. Those which contain abstracts of the current literature on that subject, and wliich will, therefore, be of greatest use to the student, are : The Journal of the Royal Microscopical Society, Zeit- schrift fur wissenschaftliche Mihroskopie, and Cenfralblaft fur allge- meine Patholor/ic nnd p body has some particular kinds of work assigned to it, which constitute its functions, and which it performs for the benefit of the whole body. The development and life-history of each part has direct reference to those functions, through which it co-operates with all the other parts in maintaining the integrity and normal activities of the whole body, all the parts being interde- pendent upon each other and subservient to the general needs. The foregoing considerations prepare us for the fact that the structure of the various ])arts of the body differs in its details. The study of those finer details can only be pursued with the aid of the microscope, for the microscopical constituents of the tissues are the elements which confer upon them their particular properties and powers. This study is called histology. Investigation has shown that there is one form of tissue-element which is always present in all parts of the body. This is the cell. It does not always possess the same form or internal structure, but in all its variations the same general plan of construction is adhered to. These cells are the essentially active constituents of the tissues. It is within them that the transformations of matter and energy are chiefly carried on, and it is due to their activities that the tissues forming the body are elaborated and enabled to perform their sev- eral functions. These marvellous powers possessed by the cell have created our conception of life, and, in spite of eager study, remain inscrutable. We do not knoAv why a living cell differs from a dead cell, but we do know that the mysterious vital powers are only derived from pre-existent living cells and are not antagonistic to the chemical and physical laws governing unorgtmized matter. All the cells of the body are descendants of a single cell, the Qgg, from which they arise by successive divisions, and throughout the existence of the body they retain some of the characters of the original cell. But as the body develops the cells of the different parts display divergent tendencies, which finally result in the for- 20 INTRODUCTION. mation of a considerable variety of tissues, grouped in various ways to form organs or systems of very different kinds of utility to the whole organism. This divergent development is known as differen- tiation and results in a specialization of the different parts of the body. Its study constitutes embryology, but it will make the com- prehension of histology easier if some of the simpler and broader facts derived from a study of development are first briefly summarized. A new individual arises through the detachment of a single cell, the ovum (Fig. 1), from the parent organism. This cell divides Fig. 1. — / Section of human ovum and its immediate surroundings within the ovary. (Nagel.) a, zona pellucida; ?), cytoplasm of the ovum ; c, granules and globules of stored food materials within the cytoplasm, collectively known as the metaplasm or deutoplasm; d, germinal vesicle or nucleus of the ovum containing, in this case, two germinal spots or nucleoli ; e, zone of epithelial cells immediately surrounding the ovum ; /, cells of the discus pro- ligerus ; .7, perivitelline spaces separating the zona pellucida from the cytoplasm of the ovum. into two colls, which, even at this stage of development, differ slightly from each other. Tliese daughter-cells in turn divide in two, and this ])rocess of division is continued, each cell giving rise to two new cells, until a considerabh; aggregate of cells lias resulted (Fig. 2). Then the cells assume a definite arrangement into layers. Some become disposed in a superficial layer enclosing the rest of the cells and a body of fluid. This layer is called the primitive ectoderm. The remaining cells accumulate in an irregular laminar mass beneath the primitive ectoderm at the site of the future em- bryo. This mass of cells is the primitive entoderm. Thus, at INTRODUCTION. 21 this stage of dovt'lopmcMit, there is a eelhilar sac, containing tiiiid, witli a reinforcement of its wall at the region occupied by the primi- tive entoderm (Fig. 3). Vu;. 2. Segmented egg of Petromyzon Planeri : Surface view of the collection of cells. The nuclei are invisible. (Kupflfer.) Subsequent to these events a third layer of cells becomes inter- posed between the primitive ectoderm and entoderm. Most of its Fig. 3. Ovum of rabbit: a, primitive ectoderm in section; 6, primitive ectoderm, surface view; c, primitive entoderm ; d, dividing cell of the ectoderm, (van Beneden.) cell s are derived from tlio.«e of the primitive ectoderm, but the 22 INTRODUCTION. ])riniitive entoderm may also participate in its formation. This third kiyer 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. mend Embryo of Necterus in cross-section, (Piatt.) ed., ectoderm ; mend., mesoderm ; c?!d., ento- derm ; a, neural groove ; ch, site of future spinal column. From these three embryonic layers of cells the body of the foetus 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 dowuAvard 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 INTRODUCTION. 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 not 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 Fio. 5. Cross-section of fish embryo. (Ziegler.) a, neural canal, cells enclosing it not represented: 6, chorda dorsalis, site of future spinal column ; ao, aorta : Bf, external layer of meso- derm ; c, c, body-cavity ; art of this cell which are very closely akin to the intelligence of more complex organisms. They also demonstrate its poAver 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, eacli 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 Rrownian movement of the granules is more con- stantly present. The cells have fixed positions and tlieir 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. TIIJ'J CELL. 31 For a similar reason, as already intimated, they can dispense with the contractile vacuole. We learn, t-lien, that when we reduce the cell to its simplest terms, it consists of a mass of cyto[)lasm enclosing a nncleus. To these we must probably add a third essential constituent, the centre- 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 justitied. 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 ; b, spongioplasm ; c, chromosome, composed of "chromatin," and forming a part of the intranuclear reticu- lum ; between these chromatic tilires is tiie achromatin ; 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 ; <;, centrosome, with radiate arrangement of the surrounding spongioplasm ; h, 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 HISTOLOGY. 1. The cytoplasnij which usually makes up the chief bulk of the cell, especially in those varieties which have active metabolic functions, appears to be the part of the cell in which the assimilated food is utilized in the production of chemical substances, either fresh cytoplasm or some other product, or in the execution of movements or the libe- ration of energy in other forms. Most of the active processes that are obvious seem to be carried on in the cytoplasm during the greater part of the life-history of the cell. 2. The nucleus appears to preside over the assimilative processes Avithin the cell. If a cell be subdivided so that the uninjured nu- cleus is retained in one of the portions, that portion may grow and become a perfect cell. But the portions that are deprived of a nu- cleus do not grow, and while they may retain life for a considerable time, utilizing the assimilated food they retain, eventually perish. Aside from this assimilative function, the nucleus appears to be the carrier of hereditary characters from the parent cell to its prog- eny during the division of the cell. This will become clearer when the process of cell-division is described. 3. The centrosome appears to be the organ presiding over the division of the cell. It inaugurates those activities in nucleus and cytoplasm which result in the production of new cells, and seems to guide them, at least during the greater part of the whole process. It is evident, from these statements, that the cell has an exceed- ingly complex organization, which a simple microscopical study can- not wholly reveal. Notwithstanding this fact, obvious microscopical differences are presented by cells which have be(iome specialized in different directions, and we must know something of the visible structure of the primitive cell before we can appreciate these depart- ures from it. The cytoplasm is not a simple substance. Its constitution is so com- plex that our present means of research are not adequate to reveal its structure. We know that its solid constituents are chiefly ])ro- teids, together with relatively small quantities of carbohydrates, fats, and salts. To these is added a large proportion of water wliich, while not entering into a definite chemical union with the other constituents, is so intimately associated with them as to form an integral part of the cytoplasm. The visible structure of cytoplasm differs somewhat in different cells, even among those that appear to be comparatively unspecial- ized. In the fixed cells of the higlier animals and man it appears THE CELL. 33 to consist of a very delicate network or reticulum of minute fibres, termed tiie si)ongioj)lasm. The points of junction of these fii)res and their optica4 cross-sections give a finely granular appearance to the cytoplasm. In the meshes of the spongio[)lasm is a clear, homogeneous sub- stance, the hyaloplasm. This may also contain some granules, but they are probably not constituent parts of the cytoplasm and are grouped under the term metaplasm. Some of them are composed of material tiiken from without, either in their original form or slightly modified ; others have been produced within the cell by chemical transformations, and are either useful products, to be sub- sequently turned to account by the cell itself or to be discharged as a secretion, or they are waste matter destined for elimination from the body. The relative proj)ortions of the hyaloplasm and the spongioplasm and the arrangement of the fibres of the latter both vary in differ- ent cells.' When seen under the microscojie the structure of the nucleus, except during the division of the cell, closely resembles that of the cytoplasm. It is traversed by a number of delicate fibres, which branch and give the nucleus a reticulated appearance. At its sur- face these filaments unite to form a delicate membranous envelope, sharply defining the nucleus from the surrounding cytoplasm, but it is a question whether this membrane is continuous, or whether it is an exceedingly close meshwork with minute apertures permitting a direct communication between the cytoplasm and the interior of the nucleus. The spaces between the nuclear filaments are occujiied by a clear, homogeneous substance, which may be identical and continuous with the hyaloplasm of the rest of the cell. One or more highly refracting bodies, the nucleoli, may be pres- ent in the nucleus, lying freely in the clear substance between the filaments or attached to the latter. Their purpose is not known, but it is thonght that they arc not essential parts of the cell but correspond more or less closely to the metaplasm in the cell-body. ' The reticulateil appearance of the cytoplasm may also he explained hy assum- ing it to have an alveolar structure, and the theory that such is its actual structure possesses much plausiliility. In that case the visihle reticulum would he formed hy the walls of the alveoli and their lines and points of intersection, all of which would be included in the spongioplasm, while the contents of the alveoli would constitute the hyaloplasm. 3 34 NORMAL HISTOLOGY. Owing to their affinity for certain coloring matters, the substances composing the nuclear filaments are called chromatin, or chromo- plasm. The hyaline substances making up the rest of the nucleus do not receive those coloring matters, and for this reason and in this situation are called achromatin. These terms are only used in a morphological sense and do not specify any definite chemical com- pounds. The behavior of the nucleoli toward dyes is somewhat different from that of the chromoplasm, which leads to the inference that they are of a different chemical nature. Except during cell-division, the nucleus usually lies quiescent within the cytoplasm, but some observers have seen it execute ap- parently spontaneous movements, and it is evidently possible for its position in the cell to vary from time to time. In marked contrast to this apparently dormant state, as far as visible alterations of structure are concerned, is the 7-6le })layed by the nucleus during the reproduction of the cell. There are two modes of cell-division, the "indirect" and the " direct," but they are by no means equivalent to each other. The former, also termed karyokinesis because of the active changes in the nucleus, appears to be the only truly reproductive process. Direct cell-division results in the formation of new cells, but they seem to lack that perfection of organization which would be required for the complete and indefinite transmission of all the characters of the parent cells. Before entering into a description of karyokinesis, a few words must be said concerning the centrosome. This is an extremely min- ute granule which is usually situated in the cytoplasm not far from the nucleus. It is often surrounded by a thin zone of hyaloplasm which facilitates its recognition among the fibres and nodal points of union of the spongioplasm. The fibres of the latter are also fre- quently arranged in a radial manner for a short distance around the centrosome. But in many instances it is extremely difficult to dis- tinguish the centrosome, and its constant presence in cells is largely a matter of inference. Sometimes the centrosome is double, the two granules lying close to each other and often being surrounded by a common clear zone of hyaloplasm. The first step in the process of cell-division by the indirect method, or karyokinesis, is a division of the centrosome into halves (Fig. 15), which separate and pass to opposite points in the cytoplasm. These points are called the poles of the cell, and when the new cen- THE CELL. 35 trosoraes reach them they are ealled the polar boches. In these situa- tions they are surrounded by a more distinct zone of hyaloplasm than that whicinenclosed the original parent centrosome, and beyond this the spongioplasm is frequently arranged in radiations of unusu- ally thick Hbres. The polar bodies witii their clear envelopes and the prominent radiations about them are collectively known as the attraction-spheres (Fig. 8). Fig. 8. --b Dividing ceU from ovum of a>-cari.< ..,.;,.;. ,„.;„:. K. .-taDctki and Siedlecki.) a, polar body, centrosonie, surrounded by a clear zone ; b, chromosomes of the dividing nucleus. Be- tween the polar bodies is the achromatic spindle, and radiating from each attraction- sphere are delicate filaments of spongioplasm. The cytoplasm presents indications of vacuolation. While the polar bodies are separating, or after they have passed into the polar regions of the cell, the nucleus begins to show those changes in structure which constitute karyokinesis. This process mav be divided into a number of phases, as follows: 1. Tlie Formation of the Spirem (Fig. 9). — This consists in a con- densation of the chromoplasm. The branches of the nuclear fila- ments are withdrawn into the substance of the main fibres, into which the nuclear membrane or ])eripheral network bounding the nucleus is also absorbed. The vesicular character of the nucleus is lost during these changes in the arrangement of the chromoplasm, which appears as a loose tangle or skein of one or more threads of uniform diameter lying freely in the body of the cell. This skein is called the spirem. The chromoplasm in this condensed con- dition stains more deeply with nuclear dyes than in the resting con- dition of the nucleus. The nucleoli in the meantime become faint and seem to ultimately disappear. They play no part in the process 36 NORMAL HISTOLOGY. Fig. 9. Fig. 10. Fig. 11. Fig. 12. Fig. 14. Fig. 1.3. Diagrams illustrating the phases of karyokiuesis. (Flemming.) Fig. 9.— Spirem. Fig. 10.— Monaster. Fig. 11.— Metakinc'sis, early stage. Fig. 12.— Metakinesis, Inte stage. Fig. 13.— Diastcr. Fig. 14.— Dispirem. The achromatic spindle is represented, but not the centrosomes (polar bodies). The cell- body is also omitted. THE CELL. 37 of cell-division, unless they participate in the formation of the achromatic s})indle. 2, The Monaster Phase (Fig. 10). — The threads of the spirem suffer a rearrangement, resulting in the formation of a sort of wreath, situated midway between the poles, in the equatorial plane, i. e., the plane perpendicular to and j)assing through the centre of a line joining the two polar bodies. This wreath is called the monaster, because of its star-like configuration when seen from above. When viewed in })rofile it appears as a band of fibres Iving in the equator. It is at first made up of a single thread or only a few threads, but subse(juently breaks into a number of similar frag- ments, called chromosomes. The exact number of these varies in different species of animal, but is constant for each species and is always divisible by two. In man it is thought to be sixteen. The chromosomes are all of nearly, if not quite, the same size, and, in the same kind of cell, closely resemble each other in shape. The most common form appears to be a V-shaped rod lying with its angle directed toward the centre of the wreath or monaster. 3. Metakinesis (Figs. 11, 12, 16). — In this phase of karyokiuesis Fig. 15. Fig. 16. Karyokinetic figures in epithelial cells. From a carcinoma removed by operation. (Lustig and Galleotti.) Fig. 15.— The centrosome has divided, but the nucleus is still in the resting condition. Five nucleoli are represented within the nucleus. Fig. 16.— Metakinesis, The polar bodies have divided. the chromosomes split along their axes into two exactly equal parts of similar shajie, and these halves separate, each passing toward one of the attraction-spheres. Meanwhile, the structure known as the achromatic spindle has been formed. This is a system of fibres resembling tho.se that have already been described as radiating from the polar bodies, but of even greater prominence. They are arranged to form a spindle 38 NORMAL HISTOLOGY. ■with its apices at the polar bodies and its equator coincident with that of the cell and the plane of the monaster. It is along the lines of this spindle that the chromosomes travel toward the centres of the attraction-spheres occupied by the polar bodies. The phases of karyokinesis that follow metakinesis are similar to those that preceded it, but occur in inverse order. 4. The Diaster Phase (Fig. 13). — The chromosomes, having reached the attraction-spheres, group themselves around the polar body to form a wreath on a plane perpendicular to the axis joining the poles. These wreaths, with the achromatic spindle, have an appearance somewhat resembling the letter H, with a long cross- piece, formed by the spindle, remaining uncolored or only faintly tinged Vjy nuclear dyes, while the uprights, made up of the chromo- somes, are deeply stained. The ends of the chromosomes now unite to form a thread, and the Avreath-like arrangement gradually passes into that of the dispirem. 5. Dispirem (Figs. 14 and 17). — The halves of the original chro- moplasm 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. 18). Fia. 17. Fig. 18. Fig. 17.— Dispirem. In this case the polar bodies have not divided (compare Fig. 16). Fig. 18.— Daughter-nuclei which have nearlj' 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 accomj)lished through a constric- tion of the body of the cell, which gra passage of Huids through those walls. The fact that the lymj)h in dilfcrent parts of the l)ody varies somewhat. THE EPITHELIAL TISSUES. 49 in composition lias led to the inference that the endothelium of the capilUiry walls exercises an active function in determining what shall pass thronry epithelium; d. lumen. The sweat-glands are simple tub\ilar glands which are coiled in their lower part to form a globular mass. Fig. -13.— Compound tubular gland : /, duct : .7, acinus. Fig. 44.— Racemose tubular gland : /,/,/, duct,« ; g, fi, acini. Fig. 45.— Simple saccular gland : /, duct ; g, acinus. 60 NORMAL HISTOLOGY. Fig. 46. Fig. 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 sliow how diflticult 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 chamcter 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, witii no trace of a lumen among the epithelial cells (Fig. 48). Glands develop from surfaces which are covered by epithelium. Fifj. 48. Section of Rlnnd from human lip. (Xadler.) a, duct, cut in slightly oblique direction (lumen oval), and probalily 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 : e, 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 ; f, acinus with crescentic group of cells with granular cytoplasm (e'), and other cells like those in 6. 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 ; /, capillary bloodvessel in the fibrous tissue. The cells of this epithelium multi])ly and penetrate into the under- lying ti.ssues, forming little solid tongues or columns ofcells( 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 con- 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 role, it differs from endothelium. CHAPTER IV. THE CONNECTIVE TISSUES. The two varieties of elemcntarv tissue that have just l)een 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: y-iven to the intercellular substances. As was stated in the introductory chapter, these connective tissues are essentially passive — /. 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 accomi)lish 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 diifer 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 ofl^spring 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 Ftg. 49. b 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 prorluced 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) TIic intcrcc'lluhir siib.staiux' is abmuhint in amount ami has receivod the special designation " matrix." According to the char- acter of tliis matrix, the cartilages have been divided into three varieties : hv;iline cartilage, fihro-cartilage, and elastic cartilage. In hyaline cartilage tiie matrix is clear and homogeneous and has the consistency of" gristle. In libro-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 {ride 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; b, matrix ; c, cells with a comi^aratively slight amount of cytoplasm, marking the transition from cartilage to fibrous tissue ; (I, pericliondrium, 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 ti.^sue 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. Fig. 51. Hyaliiif c;irliiu'_'L'. .-l-i-Uuu iiuUi human thyroid cartilage. (Wolters.) 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 matri.x. The cells in the deepest jKjrtions of the cartilage arc vacuolated, and about the groups of cells are fine granules of lime salts. In the matrix arc numerous anastomosing liiu's. 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 granting over the free surfaces of the articular cartilages. 1. Hyaline Cartilage (Figs. 49, 50, and 51). — Although under ordinary powers of the micro.>5Cope 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 haematoxylin the matrix of hyaline cartilage often acquires a flint bluish tinge, the cytoplasm of the cells a deeper shade of the same color and the nuclear chromatin a very dark l)lue. 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- po.ssess branching })rocesses, extending for THE CONNECTIVE TISSUES. 67 some distance between the Hbre.s of tlie intercellular substance, and giving the whole tissue a character closely resembling that of Fig. 52. Fibro-cartilage. Section from human intervertebral disk. (Schiifer.) 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 ordinarv fibrous tissue. 3. Elastic Cartilage (Figs, b'i and 58). — This form of cartilage Fig. 53. Elastic cartilage. Section from cartilage of human external ear. (Bohra and Davidoff.) a, cartilage-cell; 6, r. network nf elastic fibres in the intercellular suV)stance; 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 oi)en and composed of larger fibres toward the centre of the tissue than at the ])eriphery, 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. (8) The arrangement of these constituents is as follows : the organic basis of the inter- cellular substance is arranged in laminoe, which are closely applied to each other except at certain points where there are cavities, called " lacunre," giving lodgement to the bone-corpuscles. Joining these lacunre with each other are minute channels in the intercellular substances, " canaliculi," which are occupied by the fine processes of the corpuscles. In the comj)act 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 ])arallel laminie of intercellular substance, between which are the lacunae, connected with each other by canaliculi. The bone-corpuscles are nourished from the fiuids circulating in the marrf)w, which occupies the large spaces of this spongy variety of bone. It is not possible in a single pre])aration to study even these gen- eral characters of bone. The earthy salts in the intercellular sub- THE CONyECTIVE TISSUES. 69 stanoo prevent the jireparation of sections by means of the knife, and, unless they be removed, specimens of hone must l)e made; by grinding. This can best lie accomplished after the bone has been (h'ied. But T^rving the bone destroys the cor{)uscles, which appear as little desiccated masses, devoid of structure, within the lacunte. 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 Fig. 54. Ground section of dried bone. Human femur, a, Haversian canal in cross-section ; a', Ha- versian canal occupied Vjy debris ; a", anastomosing brancli from a', in neaVly longitud- inal section; h, lacuna belonging to the Haversian system, of which a' occupies the centre; c, lacuna in excentric laminae f>f bone between tlie Haversian systems. The delicate lines connecting the lacuna' are the caiialiculi. the bone be first decalcified — /. c, if the earthy salts be dissolved through the action of acids. This treatment not only removes the earthy constituents of the intercellular substance, renderino- it soft and pliable, but causes the organic constituents to swell. The effect of this swelling upon the a]>pearance of the bone is very marked. The fine canaliculi are closed and the laeunte 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 w'hich there arc 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 wath the swollen intercellular substance forming the walls of those minute channels. It is imj)ortant 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; 6, 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 laminse, which have a general parallel direction ; but there are occasional fibres of some size which pierce these laminaj in a perpendicular direction and appear to bind them together, very much as a nail Avould 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 ti.ssue itself, but merely in the arrangement of that tissue with respect to its sources of nourishment. Where the bone is massed in compact form, as in the shafts of the long bones, special means for supj)lying it Avith nourishment is provided by a series of channels, the Haversian THE CONNECTIVE TISSUES. 71 canals, which contain tlic nutrient bh)0(lves.scls, and which anasto- mose with each other tliroughout tlic whole substance of the tissue. The noui'ishin<2: lymph, derived from the blood, reaches the cells through the -x;analiculi and lacuna), 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 branch(>s connecting them with each other. It is around these lon- gitudinal Plaversian canals that the lamina) of bone arc arranged in concentric tubular layers. Each Haversian canal, with the laminne surrounding it, is known as an Haversian system. Between these Haversian systems there are excentric laminae of bone, which do not conform to the concentric arrangement of the Haversian systems. In the spongy or cancellated variety of bone the thin ])lates 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 laminre 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 finnly with the surface of the bone. The central cavities of the long bones and the spaces of cancel- lated bone are occupied by inarrow, 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 mav be said to constitute the connective tissues j)<^f 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 l^etwcen 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 gencjral 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. 73 Fig. 56. tissue, it will he of advantage to note the peculiarities of the two kinds of fibres that are found in their inter- cellular .sul)stance. The white, non-elastic fibres (Fig. 56) are exceedingly delicate, and appear, even under high powers of the microscope, as fine, trans- parent, homogeneous lines. They are usu- ally aggregated into bundles of greater or less thickness, being held together by a small amount of the cement-substance already re- ferred to. In these bundles the fibres run a somewhat wavy course from one end of the bundle to the other, but lie parallel to each other and never branch. When treated with dilute acetic acid, without previous hardening, they swell and become almost invisible. They are converted into gelatin when boiled in water. The yellow, or elastic, fibres (Figs. 57-59) are coarser than the Fig. 57. Fibres of white fibrous tissue teased apart to show the individual fibrils. Elastic fibres. Fig. 57.— From the subcutaneous areolar tissue of the rabbit. (Schafer.) Fig. 58.— Section of ear. (Hertwi^.) The intercellular substance contains a reticulum of coarse anastomosing elastic fibres. (See Fig. .%) Fig. 59.— Fenestrated membrane from a branch of human carotid artery. (Triepel.) white and more highly refracting, appearing more conspicuous when' viewed imder the microscope. They may be nearly straight, but more 74 NORMAL HISTOLOGY. usually run a sinuous course. At intervals they divide, and the branches anastomose with each other to form a fibrous network, the meshes of which may be large, as is the case in areolar tissue, or so small and bounded by such broad fibres that the network resembles a membrane pierced by somewhat elongated apertures, as is exem- plified in the fenestrated membranes of the arteries. The forma- tion of such a network is, however, not an essential characteristic of these fibres, for they appear as isolated wavy fibres in some of the fibrous tissues of open and loose structures. Elastic fibres are not affected by acetic acid, nor do they yield gelatin on boiling in water. According to Schwalbe, they have a tubular structure, con- sisting of a membrane enclosing a substance called "elastin." We may now turn our attention to the different varieties of the fibrous tissues. Fig. 60. Mucous tissue. (Ranvier.) «, stellate cells with long and branching processes; 6, elastic fibres in the homogeneous, mucoid, intercellular substance, which is not visible under the microscope unless artificially colored. Three of the cells are represented in cross-section. 1. Mucous Tissue (Fig. 60). — The cells of this elementary tissue are chiefly of the third variety mentioned above. They are spindle- shaped or stellate in form, and many of them possess processes that extend far into the intercellular substance, where they may branch and unite with the processes of neighboring cells. The predominant constituent of the intercellular substance is a gelatinous ground-substance, which contains a variable amount of mucin and appears nearly, if not quite, homogeneous under the microscope. It is this which gives the whole tissue its soft and gelatinous con- sistency. A. variable numb(!r of fibres of both the kinds already de.scribed run through this ground-substjince. The white fibres are THE CONNECTIVE TISSUES. Fro. 61. 75 — h Embryonic connective tissue fmesenchymatous tissue). (Bohra and Davidoff.) a, nucleus of stellate cell ; 6, cytoplasmic process. The intercellular substance is of gelatinous con- sistency and optically homogeneous. arranged in fine bundles, but the elastic fibres appear to be isolated, and, though they may branch, do not appear to form a network. Reticular tissue. Section through a lymph-sinus in a lymph-node of the rabbit. (Ribbert.) a, nuclei of stellate cells of the reticulum ; b, endothelial cells which are closely applied to the reticulum. The lymphoid cells, or leucocytes, have been removed from the meshes of the reticulum. Mucous tissue of a rather highly cellular character is abundant in the embryo, where it constitutes an early stage in the deyelopment of the fibrous tissues (Fig. 61). A variety less rich in cells forms 76 NORMAL HISTOLOGY. the AVhartonian jelly of the umbilical cord. It does not occur in the adult under normal conditions, except, perhaps, in the vitreous humor of the eye. 2. Reticular Tissue (Fig. 62). — The fibres of this variety of ele- mentary tissue are disposed in extremely delicate bundles, which anastomose M'ith each other to form a fine mesh work. The spaces between the fibrous bundles are filled with lymph, which is usually so crowded with cells similar to the white blood-corpuscles that the structure of the tissue is masked by their presence. The cells of this tissue are flattened and closely applied to the surfaces of the bundles of fibres, which are so fine that they simulate delicate branching processes emanating from the cells. The cement- or ground-substance is reduced to a minimum, only a small amount Iving between the fibres and the cells of the reticulum. The tissue is bounded by denser forms of fibrous tissue, with the fibrous bundles of which the reticulum is continuous. It is possible that reticular tissue contains stellate cells of the third variety mentioned as occur- ring in fibrous tissues, as well as the thin cells already described, which belong to the first variety. Where this is the case it is probable that the branching processes of those cells take part in the formation of the reticulum. Where the meshes of the reticulum are crowded with lymphoid cells — /. e., cells identical Avith some of the white corpuscles of the blood — the tissue has received the name " lymphadenoid tissue." This tissue is the chief constituent of lymph-glands and follicles, and is also found in a more diffuse arrangement in many of the mucous membranes (Fig. 107, L). 3. Areolar Tissue. — This is the most widely distributed variety of filn'ous tissue. It contains all three kinds of cells mentioned at the beginning of this section, though not always in the same relative abundance. The intercellular substance consists chiefly of bundles and laminae of fibres, which interlace in all directions. The v/hite fibres predominate over the elastic, but there are always some of the latter which either form a wide-meshed reticulum, interlacing with the bundles of white fibres, or are applied to the latter in a sort of open spiral, binding them together. In the developing tissue the cement- or ground-substance at first fills all the interspaces between the cells and the fibres ; but as development proceeds spaces appear in the tissue, which are occupied by lymjih and intercommunicate throughout the tissue. The ground-substance is then restricted to THE CONNECTIVE TISSUES. 77 a mere cement uiiitin*; the fibres within the hundles and himinie. The Hat or endothelial cells of the tissne lie within these bundles or are applied to their surfaces, forming a more or less perfect lining to the lymph-spaces within the tissue and becoming continuous with the endothelial walls of the lymphatic vessels. It is within these spaces that the lymj)h accumulates after its passage through the walls of the smaller bloodvessels, to find its way into the lymphatic circulation. The sj)in(lle-sha[)ed and cuboidal cells of the tissue lie between or within the bundles of fibres embedded in the cement- substance (Figs. 6.') and 64). Fig. 63. Areolar tissue. Preparation from the suliciitaueoiis tissue of a youns rabl)it. iScliiifer.) c', cndotliclioid ceU : />, p, eells with prrauuhir eytoiilasm ; c, c, /, cells of the fusiform or stellate variety not yet fully developert. The white fibres are in bundles imrsuiufi a wavy course: the elastic fibres are delicate and form a very open network; ^^, leucocyte of a coarsely granular variety. Areolar tissue varies greatly in different situations in the density of its structure — i.e., in the size of the fibrous bundles and their relative abundance, as compared with the number and size of the sj)acos separating them. The name is derived from that form in which the structure is open and the courses of the fibrous bundles very diverse, so that they interlace, leaving relatively large spaces between them. In this form it occurs in the subcutaneous tissues, between the muscles, forming the loose fasciie in that situation, and in many other parts of the body where adjacent structures are looselv connected with each other. The sinuous course of the in- 78 NORMAL HISTOLOGY. terwoven fibrous bundles renders the tissue easily distensible in all directions and permits considerable freedom of motion between the parts which it unites. In other situations the spaces in the tissue are smaller and the fibrous bundles closer together and less tortuous in their arrange- \\:, ment, so that the parts connected \,1v with each other are more firmly held in place. This form of the tissue occurs in all the glandular organs of the body, supporting and holding in place the func- tionally active tissues of the or- gans and constituting the chief constituents of their interstitia (see Chapter VII.). To distin- guish this form of fibrous tissue from the areolar or more open form it may be designated as connective tissue in a more re- stricted use of that term than has hitherto been employed (Fig. 65, h, b'). A still denser form of the tis- sue occurs in the fasciae and apo- neuroses, in which the fibres are aggregated in thick bundles and layers that run a comparatively straight course and are firmly held together. Ligaments and tendons differ from these only in the greater density of the fibrous bundles and in their parallel arrange- ment. These denser varieties of the tissues may be designated by a restricted use of the term, fibrous tissue. 4. Adipose Tissue (Fig. Go). — Fat or adipose tissue is a modifica- tion of the more open or loosely-textured areolar tissue, caused by the a(;(!un)ulation within the cytoplasm of the cuboidal cells of drops of oil or fat. Tiie cells which have become the seat of this fatty infiltration are enlarged, and their cytoplasm, with the enclosed nucleus, is pressed to one side, the great l)ulk of the cell being occu- pied liy a single large globule of fat. This globule, together with Cell from subcutaneous tissue of human embryo. (Spuler.) c, centrosome; fb, fibrillae in the cytoplasm of the cell ; fb', fibril detached from the cell, but evi- dently derived from it. This cell corre- sponds to c, c, and/, in Fig. 63. They are sometimes called fibroblasts because of their activitv in the formation of fibres. THE CONNECTIVE TISSUES. 79 the cytoplasm, is ciu'losetl in ii ilolicate cell-incnibrane. The fatty cells may occur singly in the midst of an apparently normal areolar tissue of the usual type, but they are more frequently grouj)ed to form '' lobulws," hold in position within the tissue by bands and layers of unaltered areolar tissue. In sections of adipose tissue prepared after hardening the tissue in alcohol the fatty globules can no longer be seen, since the alco- hol dissolves the fat from the tissues. The partially collapsed Section f:-om the tongue of a rabbit : a, a, a, groups of fat-cells forming small masses of adipose tissue in the connective tissue ; b, b', connective tissue, 6 in longitudinal, and 6' in cross-section; c, small vein containing a few red blood-corpuscles. Near the centre of the figure is another bloodvessel tilled with corpuscles. The remainder of the figure represents striated muscle-fibres in nearly longitudinal section. In the upper left hand corner these show a tendency to split into longitudinal fibres (sarcostylesi. membranes of the cells, with the cytoplasm and contained nucleus forming an apparent thickening at one side, are all that remain to distinguish the tissue (Fig. 65, a). Adipose tissue is widely distributed in the body. It serves as a store of fatty materials which can be drawn upon as a reserve stock of food when the nutrient supply of the body falls below its needs. The usefulness of the fibrous tissues can be readily inferred from their structure. The more open varieties of areolar tissue serve to give sup]>ort to the structures they unite and to the blood- ves.sels, lymphatics, and nerves sujiplied to them. They also alibrd spaces and channels for the return of the lymph, which transudes througli the walls of the capillary bloodvessels, carries nourishment 80 NORMAL HISTOLOGY. to the tissue-elements it bathes, and then returns to the blood in the veins through the interstices and lymphatic vessels contained in the areolar tissue. In pursuance of these functions, areolar tissue pervades nearly all parts of the body. Wherever bloodvessels are found, there more or less areolar tissue is present, surrounding them, giving them support, and furnishing channels for the lym- phatic circulation. As has already been stated, this areolar tissue varies in the closeness of its texture in different parts of the body. The fibrous tissues of tendons and ligaments form inextensible Fig. 66. ^m^}^'' Portion of a large tendon in transverse section. (Schafer.) a, sheath of areolar tissue sur- rounding the tendon; 6, longitudinal fasciculus of fibres within that sheath ; I, lymphatic space; c, section of a broad extension of the enshcathing areolar tissue, dividing the tendon into larger bundles; d, e, more delicate layers of areolar tissue subdividing the larger bundles of fibres. Between these areolar septa are the bundles of fibres constitut- ing the tendon. The cells which lie between the smallest fasciculi of fibres appear in stellate form ; the cross-sections of the individual fibres, among which these cells lie, are not represented. They would appear as minute dots. Ijands or cords highly resistant to tensile stress, but very ])liable. They consist of bundles of fibres lying parallel to each other and to the direction in which they are to resist pulling forces. Layers of loo.se areolar tissue penetrate the ligaments and tendons, dividing tlif-m into fasciculi, which in turn are united into larger bundles by thicker layers of areolar tissue (Fig. 60). These .sheaths of areolar tissue support the vessels and nerves supplied to the denser forms of the fibrous ti.ssue making up the ligaments or tendons. The thicker aponeuroses of the body may be regarded as broad and flat THE CONNECTIVE TISSUES. 81 lifjamont.s, in which the buiuUes of fibres run in various directions. They present a structural transition between the fibrous arrange- ment in ligaments and tendons and that in the more open varieties of areolar tit*sue. Tiie fibres of these tissues are mostly of the white variety, but in some situations, notably in the ligamentum nucha?, they are chiefiy of the elastic variety. Reticular tissue may be regarded as a special modification of areolar tissue, in which the main bulk of the tissue consists of a series of freely intercommunicating lymph-spaces. These are often densely crowded with lymphoid cells, among which the lymph slowly circulates, thereby being subjected to the modifying influ- ences of their activities. 6 CHAPTER y. TISSUES OF SPECIAL FUNCTION. The elementary tissues included in this group are highly differ- entiated in structure so as to adapt them for the performance of some special function of a high order. The constituent of the tissues -which appears most highly specialized is the cell, Avhich is often so greatly modified in structure as to have lost many of the general characters of the cells hitherto studied. Thus, for example, the cells of striated muscle are multinucleated, and the cytoplasm has become transformed into a substance known as contractile sub- stance, which occupies nearly the whole bulk of the cell, leaving only a small amount of relatively undifferentiated cytoplasm imme- diately surrounding the nuclei. In like manner the intercellular substances of some of these tissues show a complexity of structure in great contrast to those with which we have become familiar in the preceding tissues. In fact, it is stretching a point to regard the tissues lying between the cells of striated muscle as forming an intercellular substance belonging to that tissue. In this case those tissues are identical in structure with the loose areolar tissue that was described in the preceding cliapter. We may, therefore, with propriety, regard the striated muscles as organs in which the muscle-cells constitute the parenchyma and this areolar tissue the interstitium (see Chapter VII.). But in other tissues of the group there is cither an inter- cellular substance resembling those of the preceding tissues, or some special form of sustentacular tissue — c r/., the neuroglia of the central nervous system. The tissues of special function arc arranged in two groups : tlie muscular tissues and the nervous tissues. As is implied in the title, these tissues are grouped together because of their functional powers, and not with regard to peculiarities of structure, so that it is impossible to give concise statements of any common general structural characters possessed by all the members of each of these 82 TISSUES OF SPECIAL FUNCTION. 83 two <;r()iips. Thus, tlio individual mu.scnlar tissues differ consider- ably I'rom each other in structure, l)ut are closely related in fnncticju, each variety being specialized so as to execute a particular kind of contraction ^\^len functionally active. We must also assume that the variations in structure met with in the nervous system have reference to the translation of various impressions into nervous impulses, or the liberation of such impulses under different condi- tions, as W'cU as to their transmission and application to the func- tional activities of other tissues. The comi)lex functions exercised by the nervous system apj)ear to necessitate a great variety of nervous structures, and it would be a matter for sur])rise to tind the visible structure of the nervous system as simple as it is, were it not for the fact, already learned, that cells ai)parently similar in structure may have widely different, though related, functional powers. I. THE MUSCULAR TISSUES. There are three varieties of muscular tissue, which differ from each other both in structure and in the character of their functional activities. One variety is that found in the walls of the hollow viscera and larger bloodvessels. Its activities are not under the control of the will, and the cells are devoid of marked cross-stri- ation of the contractile substance. It has, therefore, received the names, " involuntary " or " smooth " muscular tissue. The other two varieties ])resent distinct and rather coarse cross-striation of the contractile substance, but differ in other structural details. One of these is called "voluntary" or " striated " muscle; the other is found only in the heart, is not under the control of the will except in rare instances, and is known as "cardiac" muscular tissue. 1. Smooth Muscular Tissue. — This elementary tissue is composed of elongated or fusiform cells, which gradually taper to a sharp ])«)int. The body of the coll, except close to the ends of the nucleus, consists of a modified cyto]>lasm, called "contractile substance," which stains a coppery red with eosin, and presents fine, indistinct, longitudinal and transverse markings, possibly the optical expression of certain ridges that are in contact with similar ridges on neigh- boring cells. Each cell has a single, greatly elongated, rod -shaped nucleus situated in its centre, with the long axis coincident with that of the cell (Fig. 67). The nuclei are vesicular and possess 84 NORMAL HISTOLOGY. Fig. 67 a distinct intranuclear reticulum of chromatin. The intercellular substance is a mere cement of homogeneous character. The cells are arranged with their long axes parallel to each other and with the tops of their minute ridges in contact, so that fine channels exist between the contiguous cells. This is apparently a provision for the circulation of nutrient fluids between the cells (Fig. 68). Smooth muscular tissue occurs in the form of bundles or layers, in each of which the cells or fibres run in the same direction. The tapering ends of the individual cells interdigitate with each other, masking the intercellular substance, so that the tissue appears as though wholly composed of cells. Surrounding the muscular bundles or between the layers of that tissue is vascularized areolar tissue, giving it support and containing its nerve-supply. The microscopical appearances of sections of smooth muscular tissue depend upon the direction in which the individual cells have been cut. A brief analysis of the different appearances that may result will be useful as an Fig. 08. Smooth muscular tissue. Fig. G7.— An isolated fibre from the muscular coat of the small intestine. (Schafer.) The nucleus is somewhat contracted, so as to appear broader and shorter than when in the extended state. Fig. f)8.— Cross-section of smooth muscular tissue ; human sipmoid flexure. (Barfurth.) Two of the muscle-cells have been cut in the region occupied by the nucleus, which appears in round cross-section. The other cells have been cut between the site of the nucleus and the end of the cell. The structural details of the cytoplasm or contractile substance are not represented, but the connecting ridges of the cells, with the channels between them, are shown. These minute ridges can, however, only be seen when the tissue has been exceptionally well preserved and is studied under a higli power of the microscope. illustration of the way in which microscopical appearances must be interpreted in order to gain a correct conception of the structure TISSi'KS OF ^ri'X'IAL FLWCTIOy. 85 of an object under observation. It is rarely that sections hap])en to be made in such a direction that they reveal the complete struct- ure of an object. It is nearly always necessary to study the iijiijcar- ances presented by the section, and to infer what tlu; structure (»f the object must be in order to yield the appearances seen. This is sometimes a matter of considerable difficulty. If the ])lane of the section lie parallel with the long axes of the cells, the nuclei of the latter will appear as rod-like or long, oval bodies lying parallel to each other and distributed at regular intervals throughout the tissue. The outlines of the cells will be distinctly visible in some places, but in most of the section the boundaries of the deeper cells will be obscured by the bodies of the cells at the surface of the section, and the borders of the latter will be difficult of detection, because in many ])laces the knife has left oidy a portion of the cell with a very thin and trans})arent edge (Figs. 69 and 70). For the practical recognition of the tissue, when cut in this direction, Ave must, theref(H'e, in many cases, depend solely upon the shape and distribution of the nuclei and the color of the material between them after the section has been treated with certain stains [e. g., eosin). If the cells of the tissue have been cut perpendicular to their long axes, the section will contain true cross-sections of the indi- vidual fibres. These appear as round, oval, or, more usually, polygonal areas of various size, according to the part of the cell included in the section. If the cell has been cut near one of its ends, the cross-section will lie small ; if near the middle, it Mill be large, and will contain a cross-section of the nucleus, situated near its centre and appearing as a round dot (Fig. 71). It is in such sections that one may sometimes see the minute prickles or ridges, already referred to, projecting from the cell-bodies and joining with those of the contiguous cells to form delicate bridges across the narrow intercellular spaces. The only tissue with which this aspect of smooth muscular tissue is liable to be confounded is dense fibrous tissue, as seen in the cross-sections of tendons or ligaments (Fig. G<)). There we also see polygonal areas of various sizes, separated for the most part by only a thin layer of cement. But these areas never contain nuclei, because they are composed, not of cell-bodies, but of intercellular substance. The nuclei of the flattened connective-tissue cells may be seen here and there apparently lying within the cement, the body of the cell being 86 NORMAL HISTOLOGY. FiCx. f)9. h a o I" d Dia^ams illustrating the appearance of a longitudinal section of smooth muscular tissiie. The distance between the lines A A and B B in the upper figure represents the thickness of the section, the line vl .1 heing in the plane of its upper surface. The line C't' in the lower figure is in the plane of tlie transverse section represented in the upper figure. It will )n; noticed that only portions of the cells, /), a, <1, r and /, will l)e ccmtained in the lonffitudiiial section (lower figure). The upper cut surfaces of those cells will ajipear as oval areas when seen from above, h', a', d', c',/'. Where the edges of those sections are thin— e. f/., a— the outlines of the corresponding oval ( focus. Fig. 77.— Termination of a muscle-fibre in tendon. (Kanvier.) c, contractile substance; p, retracted end of contractile substance, separated from the sarcolemma during the prep- aration of the specimen ; m, sarcolemma, slightly wrinkled ; s, sarcolemma in contact with fibrous tissue of tendon ; t, tendon. 92 NORMAL HISTOLOGY. FifJ. 78. J- J J- Q Q JlllliiliUUUIiUi^^ i. Fia. 94. Termination of nerves by free ends. (Retzius.) 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 ; bf/, fibrous tissue underlying the epithelium. ment.s, which branch and finally end among the tissne-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 graiuilar material containing two sorts of nuclei. This whole structure lies in close relations to the con- tractile siibshinc(; 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- Fio. 95. Motor-plate. Tail of a squirrel. (Galeotti and Levi.) n, two branches of axis-cylinder ter- minating in a plexus of varicose filaments; b, muscle-nucleus; r, 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). Tiie nerves of sensation, like those supplying the striated muscles, end in bodies in which the nervous terminations are associated with cellular structure.'* of peculiar form. Their consideration will be postponed until the structure of the nervous system is described. CHAPTER YII. THE ORGANS. Ix 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 neiwes 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 — wliich 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 suj)})ly 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 apj^ears 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 wall 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 orran. 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 fibrillee 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 chordse tendinese. 2. The Arteries. — It will l)e 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 layers. 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 layer 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 })ortion containing the nucleus projects slightly into the lumen of the vessel. The subendothelial fil)rous tissue forming the second layer of the intima is composed of very delicate fibrils, closely packed together, with a little cement l)etween them, and enclosing irregular spaces in which the iji-anching cells of the tissue lie. Elastic fibres, spring- FiG. 96. Branch of splenic artery of a rabbit: o, internal endothelial surface of the intima; 6, 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 arterj-. 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 clastic 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 a])pearance 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. Portion of a transverse section of a human lingual artery from an adult. (Griinstein.) a, intima; 6, media; c, adventitia; d, endothelium; e, subendothelial stratum (delicate areolar tissue) ; /, tunica elastica interna (fenestrated membrane belonging to the intima) ; g, stratum subelasticum containing elastic fibres (h) that pass from the fenestrated mem- brane into the media; i, concentric elastic fibres within the media; j, smooth muscular fibres of media with elongated nuclei; t, white fibrous tissue in media; Z, 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 Avithout restricting the mobility necessary for their functional activity. THE CIRCULATORY SYSTEM. 113 In the larger arteries the iiuiscle-fibres of the media are groujjed in bundles, which are separated by white and elastic fibrous tissue (Fig. 97). The muscle-fibres themselves are less highly developed than in the smnller arteries, so that the vessels are less capable of contracting, but are more highly elastic, because of the greater abundance of clastic fibres. In these larger arteries the boundary between the media and the intinui is less sharply defined than in the smaller arteries, the elastic tissues of the two coats being more or loss 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 })artially 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 prol)- 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 Avhieh 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 considera1[)le 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 lymj)h-nodes arc 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- TUE CIRCULATORY SYSTEM. 115 pression at one point, called the " hilus." It is invested by a fibrous capsule, which is ot" areolar character externally, where it connects the node with surrounding structures, but is denser, and frequently reinforced by .1 few smooth muscular fibres internally. Extensions from this capsule penetrate into the substance of the node, forming " trabeculae," 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, in the Fig. 98. I ■•»- ■ « Ih -■ - ... ^' ~b 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 ;, 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, s, 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.'prescnt, 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. 6, bloodvessels. form of anastomosing strands, which make a coarse meshwork of lymphadenoid ti.ssue in the medullary portion of the node (Fig. 99). The trabecnlse springing from the capsule penetrate the sub.stance 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 trabeculse 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 Portion of the mecIuUa of a lymph-node. (Recklinghausen.) a, a, a, anastomosing columns of lymphadenoid tis.sue; b, anastomosing extensions of the cortical trabeculse ; 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 trabeculse and their extensions in the medulla, are lined with endothelium, and a somewhat similar, but probably much less complete, lining may partially separate the sinu.ses 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 sinu.ses 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 p;roup«; : first, small t\vi<;s wliicli enter at the ])eripherv and are dis- tril)nte(l in the eapsnle and til)rons tissncs of" the trabecular and the medulla ; and, second, arteries which enter at the hilus, pass through the sinuses, an7l are distributed in the lyniphadenoid 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-meduUated 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 fre(juent 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. Fio. 101. @/?i) ^^'y^ mmMm Fig. 100.- Portion of lympli-foUiclc from mesentery of ox. (Flemming.) z. peripheral zone of small, closely apffreRated 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 / is a cell executing amceboid locomotion, p z, pigmented cell, which has taken up colored granules from oiitside: tk, 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 Avith delicate fibres given off from the tissues of the capsule and trabeculae (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. e., cells possessing the power of amoeboid move- ment and capable of incorporating foreign substances — or are con- FiG. 102. .--■■:>H /f'tii;© v^m Section of red marrow; human. (Bohm and Davidoff.) a, a, erythroblasts ; ft, 6, myelocytes ; V, myelocyte undergoing division ; c, giant-cell with a single nucleus ; c', giant-cell with dividing nucleus ; d, reticulum ; e, space occupied by a fat-cell (not represented) ; /, gran- ules in a portion of an acidophilic cell. veyed into the marginal portions of the follicles, where, if insus- ceptible of destruction, they remain. It is in consequence of this process that the lymph-nodes connected with the bronchial system THE CIRCULATORY SYSTEM. 119 ot" lymphatics iiro blackened a.s the result of an accumulation of particles of carbon that liave been inhaled and then absorbed into the lymphatics. The lymplr-nodes may, therefore, be considered as filters which remove suspended foreign particles from the lymph ; but it is l)robable that the dissolved substances in the lymph are also affected in its passage through the nodes, and that a purification of that Huid is thereby occasioned. A fresh access of leucocytes further alters the character of the lymph during its transit through the lymph-nodes. Bone-marrow (Fig. 102). — In early life the medullary cavities of the long bones, as well as the cancellae of the spongy bones, are all occupied by that form of marrow known as " red " bone-marrow. This is functionally the most important variety. In after-life the marrow in the medullary cavities of the long bones becomes fatty through infiltration of its cells with fat, which converts them into cells quite similar to those of adipose tissue. Marrow so modi- fied is called " yellow " marrow. It may subsequently undergo a species of atrophy, during which the fat is absorbed from the cells and the marrow becomes serous, fluid taking the place of the mate- rials that have been removed. This process results in the produc- tion of a " mucoid " marrow. The marrow of bones possesses a supporting netAvork of reticular tissue not unlike that of the lymph-nodes. In the meshes of this tissue are five different varieties of cell (Fig. 103) : First, myelo- cytes, cells resembling the leucocytes of the blood, but somewhat larger in size and possessing distinctly vesicular nuclei. They are capable of amoeboid movements, and not infrequently contain gran- ules of pigment which they have taken into their cytoplasm. Second, ervthroblasts, or nucleated red blood-corpuscles, which divide by karyokinesis and eventually lose their nuclei, becoming converted into the red corpuscles of the circulating blood. Third, acid()})hllic cells, containing relatively coarse granules having an affinity for " acid " anilin-dyes, such as eosin. These cells are larger than the majority of the leucocytes circulating in the blood. Their nuclei are spherical or polymorphic and vesicular. Fourth, giant-cells with unusually large bodies and generally several nuclei, though occasionally only one nucleus is present. They possess the power of executing amoeboid movements and appear to act as phago- cytes. Where absor})tion of bone is taking place they are found 120 NORMAL HISTOLOGY. closely applied to the bone that is being removed, and have in this situation been called " osteoclasts." Fifth, basophilic cells, or plasma- cells, the cytoplasm of which contains granules having an affinity Fig. 103. Cells from bone-marrow : o, small leucocyte from circulating blood, with highly chromatic nucleus and slight amount of cytoplasm, a " lymphocyte " probably derived from a lymph- node ; 6, 5, myelocytes, larger than a, with vesicular nuclei ; c, c, c, erythroblasts, with nuclei in karyokinesis ; c', mature red corpuscle (erythrocyte) ; d, acidophile (eosinophile) leucocyte. The basophilic leucocytes, or plasma cells, resemble this, but have smaller and less abundant granules of different chemical nature; e, giant-cell (myeloplax) with three nuclei ; a, 6, c, and d, from the marrow of the fowl (Bizzozero), the red corpuscles of which are oval and nucleated, c'; e, from the marrow of the guiuea-pig. (Schafer.) for " basic " anilin-dyes, such as dahlia. These cells are relatively large, and possess vesicular and frequently polymorphic nuclei. Aside from these cells, which may be regarded as forming a part of the marrow, it contains red blood-corpuscles and leucocytes, either formed within the marrow or brought to it by the circulating blood. The functions of the various cells in bone-marrow have not been finally determined, but it is certain that the erythroblasts, by their multiplication and transformation, maintain the supply of red cor- puscles circulating in the Ijlood. The arteries supplied to tlie marroAv divide freely and open into small capillaries, which appear subsecpiently to dilate, and either to blend with the endothelial elements of the reticular tissue or to become pervious through a separation of the cells forming their walls. In cither case the blood passes into the meshes of the retic- ular tissue, where it slowly circulates among the constituents of the marrow. It then passes into venous radicles devoid of valves, and is thence conveyed from the bone. In some animals — e. r/,, birds — the production of red corpuscles appears to be confined to the venous THE CIRCULATORY SYSTEM. 121 radicles (Fijx. 104). The veins Icavint^ the iiones are abundantly snpplied willi valves. Fio. 104. Section of small venous radicle in marrow (if the fowl. (Bizzozero.) Just within the vascular wall is a zone of leucocytes, one of which contains a karyokinetic figure. Within this zone is a second zone of erythroblasts, four undergoing division, and in the centre of the lumen are a number of matured red blood-corpuscles (containing nuclei in the case of birds). The cytoplasm of the leucocytes contains no haemoglobin, while that of the erj-throblasts does. In birds and, probably, in other classes of animals the marrow of the bones is one of the sites for the production of leucocytes as well as red corpuscles. The latter are not produced from the former, but only from the erythroblasts, which con- stitute a distinct variety of cell. Throughout life the cancellated portion.s of the flat bones and of the l)odies of the vertebrae contain red marrow, but the shafts of the long bones are occupied by the yellow variety, which has lost its power of producing red blood-corpuscles and leucocytes, and has, therefore, become functionally passive. CHAPTER IX. THE BLOOD AND LYMPH. The blood consists of a fluid, the plasma, in which three sorts of bodies are suspended : the red corpuscles, the leucocytes or white corpuscles, and the blood-plates. The plasma is a solution in water of albuminous and other sub- stances. Some of these are of nutritive value to the tissues of the body. Others have been received from those tissues, and are on their way toward elimination from the body. Still other con- stituents have passed into the blood from one part of the body, and are destined to be of use to other parts. In the smaller vessels, while on its course through the circulatory system, portions of the plasma make their way through the vascular walls and form the fluid of the lymph. This passage appears to be, in part, a simple filtration through the walls of the vessel, or the result of osmosis ; in part, the result of a species of secretion Fig. 105. Yj C Red corpuscles from human blood. (Bohm and Davidoff.) a, optical section of a red blood- corpuscle, seen from the edge ; h, surface view. (The bounds of the central depression are made a little too distinct in this figure, ns is evident from an inspection of a.) c, rouleau of red corpuscles. When undiluted blood has remained quiescent for a few moments the red cori>uscles arrange themselves in such rows, probably because of the attraction which they, in common with other bodies suspended in a fluid having a nearly identical sf)ecific gravity, have for each otlier. effected by the endothelial cells lining the bloodvessels, these cells promoting the escape of certain constituents of the plasma and restraining or preventing that of others. In the exercise of this secretory function the endothelia in different parts of the vascular system appear to act differently, the composition of the fluid passing through the walls of the vessels not being exactly the same in all parts of the body. It is still a question, however, in what degree 122 THE BLOOD AM) JAMl'JI. 123 the onclothcHal cells arc active in briiij^in^ about these differences. Their character is not su(;h as would be expected of cells carrying on active processes. The red corpuscles are soft, elastic discs, with a concave imjircs- sion in both surl'aces (Fig. 105). They are slightly colored by a solution of ha'inoglobiu, and are so abundant that their presence gives the blood an intense red color; but when viewed singly under the microscope each (;orpuscle has but a moderately pronounced hkI- dish-yellow tinge. The haemoglobin solution is either intimately associated with the substance composing the body of the corpuscles, called the " stroma," or it occupies the centre of the corpuscle and is surrounded by a pellicle of stroma. Under normal conditions the red corpuscles, in man and most of the mammalia, are not cells, for they possess no nuclei, nor are they capable of sj)ontaneous movement or multiplication. They are, rather, cell-products, being formed either within the cytoplasm of cells of mesoblastic origin, or by the division of cells derived from the mesoblast, and called erythroblasts, the descendants of which become converted into red corpuscles through an atrophy and disappoamnce (probably expulsion) of the nuclei and a transforma- tion of the cytoplasm into the stroma, which take place after the elaboration of the haemoglobin within the cell. The former, or intracellular, mode of production occurs in the embyro, even before the complete development of the bloodvessels ; the latter mode of production seems to be the only one occurring in the adult, the chief location of the erythroblasts appearing to be in the red marrow of the bones, where they are situated either in the tissues of the marrow itself, whence their descendants, while still cellular, pass into the vessels, or in the large venous channels of the marrow, where the blood-current is sluggish and the erythroblasts remain close to the vascular walls. In some antemic conditions the erythroblasts ap- pear in the circulating blood, where they may be distinguished from the normal red corpuscles by the presence of their nuclei and, fre- quently, also by a difference in size (see Fig. 103, c). In the reptilia and birds the red corj>uscles are normally nu- cleated ; but, though morphologically resembling cells, they are incapable of multiplication or spontaneous movement, and have undergone such modifications that they arc not cells in a physiolog- ical sense. The functional value of the red corpuscles is dependent upon the 124 NORMAL HISTOLOGY. hEeraoglobin they contain, which is said to constitute 90 per cent, of their solid matter. It is readily oxidized and reduced again, and serves to carry the oxygen of the air, obtained during the passage of the blood through the pulmonary capillaries, to all parts of the body. The red corpuscles, therefore, subserve the respiratory function of the blood, as the plasma subserves its nutritive func- tion. The leucocytes, or white blood-corpuscles, are cellular elements closely resembling the amoeba in their structure, which are present in the blood in much smaller number than the red corpuscles, the usual proportion being about one to six hundred. They vary some- what in size and structure, either because of differences in their origin, or because they are in different stages of development. The majority of them are capable of amceboid movements ; but while they are cir- culating in the more rapid currents of the blood the constant shocks they receive through contact with other corpuscles or with the vascu- lar walls keep their cytoplasm in a contracted state and they maintain a globular form. If, however, through any chance they remain for some time in contact with the wall of a vessel, they are able to make their way between the endothelial cells and pass out of the circulation into the surrounding tissues. Here they creep about, and for this rea- son liave been called the migratory or wandering cells of the tissues. They ultimately either suffer degenerative changes and disappear, or find their way back into the circulation through the lymphatic channels. During these excursions they may incorporate stray particles in the tissues, and thus act as scavengers. This activity has been called their phagocytic function, and may play an impor- tant part in the removal of material that should be absorbed or of particles that would otherwise be injurious to the tissues ; e. (/., bacteria. (See statements regarding the nature of colostrum-cor- puscles.) The emigration of leucocytes from the bloodvessels is pronounced in many of the inflammatory processes, and their phagocytic func- tion may have a marked influence on the result. The leucocytes are produced in the lymphadenoid tissues of the body, the lymphatic glands, thymus, spleen, and the more diffusely arranged tissues of like structure, but probably most abundantly in the red marrow of the bones. A close study of the leucocytes has resulted in their subdivision into a number of groups according to their morphological differences THE BLOOD AM) LYMPH. 125 or to peculiarities in their behavior toward eoh)ring-matter^«. Tlie best defined of these groups are : 1. The pol3muclear neutrophilic leucocytes, in which the nucleus has a very i-rregiiiar form, often presenting the appearance of two or more nuclei, and the cytoplasm contains gnmides that have an affinity for neutral aniliii-dyes (Fig. 106, / and (/). This variety con>titnt('s about 72 per cent, of the total number of leucocvtes, and is prol>ably produced chieHy in the red marrow of the bones. They Fig. 106. Leucocytes from normal human blood. (Bohm and Davidoft'.) a, red blood-corpuscle, intro- duced for comparison ; b, small mononuclear leucocyte (lymphocyte) ; c, large mono- nuclear leucocyte ; g. polynuclear leucocyte. These ditfer in the character of the granules they contain (not represented in the figure). In normal blood those granules are neutro- philic in the vast majority of the polynucleated leucocytes. OccasionaUy they are acido- philic, "esinophile leucocytes" ; sometimes basophilic, "maht-cells" or "plasma-cells." d, e,/, intermediate and probably transitional forms between the large mononuclear leu- cocytes c, and the polynucleated leucocytes, or leucocytes with polymorphic nuclei, g. possess the power of executing amoeboid movements and incor- porating foreign particles. 2. The lymphocytes, with a single round nucleus and a little clear cytoplasm around it. The.se leucocvtes are of about the same size as the red blood-corpuscles (Fig. 106, b). They are derived from the lymphadenoid tissue in the lymph-nodes and other situations, and appear to be incapable of amaboid movement. They constitute about 23 per cent, of the total number of leucocyte-s in normal blood. 3. The large mononuclear leucocytes, which are larger than the red corpuscles and have oval nuclei suri\)unded by clear cytoplasm (Fig. 106, c). This variety has also received the name " myelocyte,'' on the probably correct assumption that they are derived from the red marrow of the bones. They are capable of passing through 126 NORMAL HISTOLOGY. transitional forms until they acquire the characters of the polynuclear neutrophilic leucocytes described above. The large mononuclear leucocytes, together with the transitional forms, make up about 3 per cent, of the normal number of leucocytes. 4. The eosinophilic leucocytes (Fig. 103, d), also larger than the red corpuscles, with irregular, polymorphic nuclei, and a cytoplasm containing relatively large granules which hav^e an affinity for acid dyes ; c. //., eosin. These are frequently seen in unusual numbers around inflammatory foci or in tissues undergoing involution; e.g., in the connective tissue of the breast when lactation is suspended. Their significance is not understood, but they appear to be derived from the red bone-marrow. They constitute from 1 to 2 per cent, of the total number of leucocytes. 5. Basophilic leucocytes, occasionally met with, which are charac- terized by the presence of granules in the cytoplasm having a .special affinity for basic anilin-colors. These cells have also received the names "mast-cells" and plasma-cells, but the latter term is indefinite, having been applied to a number of cells of different nature. The blood-plates are colorless round or oval discs, about one- fourth the diameter of the red corpuscles. Their function has not been definitely determined, but it is thought that they may play a role in the production of fibrin, perhaps by the liberation of fibrin-ferment. Minute globules of fat are occasionally present in the blood, especially during digestion. The lymph, like the blood, consists of a fluid portion, the plasma, and corpuscles held in suspension. The plasma, as would be anticipated from its origin, is very similar in composition to that of the blood. The corpuscles are, for the most part, identical with the small leucocytes (lymphocytes) of the blood, which derives its supply of those cells from the lymph flowing into it. The chyle is the lymph found in the lacteal lymphatics during digestion. AVhen absorption of the products of digestion is in progress this lymph contains a great number of globules of fat, some S(j minute as to l)e barely visible under the microscope. In the intervals between absorption this lymph does not differ from that found in the other lymphatics of the body. Fibrin may present the appearance of a delicate network of ex- tremely fine fibres, somewhat resembling a cobweb (Fig. 268), or these THE BLOOD ASD LYMPH. 127 fibrils may be acrcrreffatod into larger threads variouslv interwoven, or they may be still further condensed to lorm masses of a hyaline character. The fibres may undergo a disintegration into granules, mIu'u their -til)rin()iis nature is not readily revealed. Fibrin is not found in the body under normal conditions, but separates from the blood if the circulation be arrested for any considerable length of time. It appears to be the result of the interaction of four sub- stances : fibrinogen, fibrinoplastin, fibrin-ferment, and salts of lime. The latter are always present in the tissues ; fibrinogen exists in the plasma of the blood and lymph, and is, therefore, very widely distributed. The fibrinoplastin is believed to be derived from the bodies of cells that have undergone some destructive change ; and tlie ferment may be derived from the same source. These four substances are present when the flow of blood through the ves- sels has been seriously checked for a considerable period ; fibrin is then formed, causing a coagulation of the blood. Such a clot, within a vessel during life, is called a " thrombus." Coagulation takes jilace more rapidly if there be a destruction of tissue ; e. g., a break in the wall of the vessel. It may also be occasioned by a roughness on the internal surface of the vessel, if the flow of blood over that obstruction is seriously retarded. In such a case the fibrin-forming elements may be liberated from the bodies of leuco- that find lodgement behind the obstruction and suffer injury, or they may be derived from blood-plates that have been arrested and undergone similar changes. In a like manner, fibrin may be formed in the lymphatic vessels or the interstices of the tissues.* ' An explanation of fibrin-formation, ofTered by Lilienfeld, would serve to elucidate many ca.ses of coagulation under morbid circumstances. According to this observer, fibrin is formed by the union of '' thrombtisin " with calcium, and is, therefore, a calcium-thrombosin compound. The thrombosin is produced from fibrinogen by the action of nuclein, which in turn is formed from the nucleoliiston contained in the nuclei of cells. Coagulation, then, would be the result of the following process : the nucleoliiston in the nuclei, during "karyolysis" or disintegra- tion of the nucleus, is decomposed into " histon '" and nuclein. The latter, acting on fibrinogen, produces thrombosin, which unites with calcium to produce fibrin. CHAPTER X. THE DIGESTIVE ORGANS. The digestive tract consists of six holloWj and for the most part, tiibulcir organs, which successively open into each other and extend from the pharynx to the anus. The food, after mastication and admixture with saliva in the mouth, passes through (1) the oesoph- agus into (2) the stomach. Here it undergoes digestive changes under the influence of the gastric secretions. Thence it passes into (3) the duodenum, where the secretions of the liver and pancreas and other glands are mixed with it and still further fit it for absorption. From the duodenum it enters (4) the small intestine, the walls of which take up the available products of digestion, and thence passes into (5) the colon. In the latter the fluid portions are gradually absorbed and the relatively dry residue, the faeces, passes out of the body through (6) the rectum and the anal orifice. The walls of the digestive organs have a general similarity through- out the whole of the digestive tract. They consist of four coats : 1, an internal mucous membrane; 2, a submucous coat; 3, a muscular coat ; and, 4, either a serous or a fibrous external coat. These coats are, respectively, continuous with each other throughout the whole tract. The internal coat, or mucous membrane, varies in both structure and function in the different organs, and will, therefore, re- quire closer study than the other coats. The latter have nearly the same structure in all the organs. The submucous coat is made up of areolar fibrous tissue, which permits some freedom of motion between the mucous and muscular coats, and contains the larger bloodvessels and lymphatics that supply all the coats. The mus- cular coat consists, in general, of two layers of smooth muscular tissue : an internal circular layer and an external longitudinal layer. Its function is to prodtu^e those vermicular or peristaltic move- ments which mix and gradually propel the food along the digestive tract. The external coat is smooth and serous over those portions of the trac;t which retpiire the greatest freedom of motion. It is nowhere complete, but, where present, is really a portion of the 128 TlIK DIGESTIVE ORGANS. 129 pcritonoiiiu wliich partially ('nvel()[)s the; organs that are contained in the ahdoniinal cavity. Where this serous covering is wanting the external coat consists of areolar fibrous tissue, which serves to connect the ^)rgans of the digestive tract with neighboring struct- ures, and thus becomes continuous with the areolar-tissue system pervading the whole body. It supports tiie vessels and nerves which niaUe their way through it to the different (jrgans. In addition to the organs above enumerated, it is appropriate to consider here the structure of the tongue, pharynx, salivary glands, and pancreas. 1. The tongue consists chiefly of voluntary muscles, the fibres of which are grouped in bundles running in various directions through the substance of the organ. Between the individual striated mus- cle-fibres, and also between the bundles into which they are col- lected, there is a variable amount of areolar fibrous tissue contain- ing fat, nerves, and bloodvessels (Fig. 65). This areolar tissue Fig. 107. Fig. 108. Sections of papillae of tongiie. Fig. 107.— Filiform papilUt ; human. Heitzmann.) Fig. 108.— Fungiform papilla; ; human. (Heitzmann.) E, stratified epithelium; C. injected capillaries within the fibrous tissue of the papilla; L, lymphadeuoid tissue in lower portion of mucous membrane ; M, muscular tissue of the tongue. is more abundant near the surface of the tongue, and is covered with a layer of stratified epithelium, thicker at the sides and on the dorsum of the tongue than on its under surface, where it becomes 130 NORMAL HISTOLOGY. continuous with the stratified epithelium covering the gums and lining the buccal cavity. Fig. 109. Two circumvallate papillse ; rabbit. (Ranvier.) p, p', fibrous tissue extendinginto the papilla ; p', that containing the nerves passing to the taste-buds ; g, taste-buds ; v, small vein ; n, n, nerves ; a, acini of a serous gland. The upper surface and the edges of the tongue are covered with papillee, some of which are pointed (filiform papillae), others rounded Fig. 110. Portion of a section of a mucous gland in the human tongue. (Benda and Guenther's Atlas.) a, duct ; b, acinus opening into a duct-radicle ; c, acinus lined with mucigenous cells, sim- ilar to h. Between and below a and c, cross-section of a small artery, recognizable by the elongated nuclei of its muscular coat. (fungiform papilla?), and .still others surrounded by a sulcus (cir- cumvallate papilke) (Figs. 107-109). AVithin the epithelium lining THE DKJKSTIVE ORG ASS. 131 this sulcus are peculiar groups of colls, called taste-buds, which will he described in a subsequent chapter. At the junction of the middle and posterior thirds of the upper surface of the tongue there are several of tiiese circumvallate papillae which are of muisual size. Within the subepithelial areolar tissue, and often extending for some distance between the muscles, there are, here and there, small racemose glands, which secrete a serous or mucous fluid (Figs. 109, a and 110). They are most abundant on the back and sides of the pos- terior part of the tongue, and their ducts frequently open into the sulci of the circumvallate papilla\ Within the subepithelial areolar tissue small collections of lymphadenoid tissue (lymph-follicles) are also of not infrequent occurrence. The papillae covering these are low and inconspicuous, so that the surface of the tongue appears unusually smooth at those points. 2. The salivary glands belong to the racemose variety of secreting glands. The secretions which they furnish are of two kinds : 1, a thin, serous fluid, containing albuminoid materials, among which are the specific ferments elaborated by the gland ; and, 2, a viscid fluid containing mucin. These two secretions are furnished by acini lined with different varieties of epithelium. The parotid gland secretes onlv the serous fluid, and is composed of serous alveoli. The sub- liuffual g-land secretes onlv the mucous fluid ; but the submaxillar^' gland secretes both, and, therefore, contains both serous- and mucous-secreting cells. The cells which line the mucous acini have clear bodies, as the result of a storage of trans])arcnt globules of mucin or mucigen within the cytoplasm. Where these globules are abundant the nuclei of the cells are crowded toward the attached ends of the cells. When the mucin is discharged from the cells they become smaller, less clear, and more granular in appearance. At the periphery of the acini, and especially well marked at or near their blind extremities, are, here and there, crescentic, granular epithelial cells, which may reach the lumen of the acinus or be crowded back by the enlarged cells adjoining them. These cells form the " crescents of Gianuzzi." In the submaxillary gland, at least, many of these crescents secrete the serous or albuminoid fluid mentioned above. This secretion reaches the lumen of the gland through minute intracellular channels (Fig. 111). The serous alveoli of the salivary glands are lined M-ith cells that, 132 NORMAL HISTOLOGY. at certain stages of their activity, are so crowded with granules that the nuclei are obscured. These granules are the accumulated mate- rial from which the secretion is formed, and when the gland has been functionally active for some time they diminish in number, Fig. 111. Section of an acinus of the human submaxillary gland. (Krause.) The lumen is surrounded by mucous cells, containing globules of mucigen. Two groups of Gianuzzi's crescents are represented, with the intracellular channels conveying the serous secretion to the lumen. and the nuclei then come into view. At the same time the cells become smaller, and the lumen within the acinus, which at first was barely distinguishable, becomes more obvious. The epithelium lining the acini of all the salivary glands rests Fig. 112. Diagrammatic representation of a portion of a human submaxillary gland. (Krause.) a, duct,, lined with columnar cells, striated at their Vjases and passing into a more cubical epithe- lium without .such striation ; 6, mucous cells; c, serous cells; d, crescent; e, basement. membrane. In this figure the convoluted course of the ducts and tubular acini has been ignored, and they have been represented as though lying in a single plane. upon a modified connective tissue, called tlie " basement-membrane," which consists of flattened cells arranged to form a broad, mem- branous reticulum, the meshes of which are filled with cement. Outside of this basement-membrane there is a small amount of THE DIGESTIVE ORGANS. 133 vascular areolar tissue, and broader bands of that tissue divide the ^vllole gland into small lobes and these again into still smaller lobules (Fig. 25). The duet>''of the salivary glands are lined with columnar or pyram- idal epithelial cells, the attached ends ot" which often show a stria- FiG. 113. a-! i^k^0^^^^ Part (if a cross-scctiou of thu a-sophagus of a dog. (Bohm and Davidott'.j «, mucous mem- brane: 6, submucous coat ; c, muscular coat; rf, fibrous coat; e, stratified epithelium;/, subepithelial areolar tissue (sometimes called the "tunica propria " of the mucous mem- brane) : g. muscularis mucosK; h, areolar tissue of the submucosa, containing the chief branches of the arterial and venous vessels; (, internal, encircling layer of the muscular coat. It is the contraction of this coat that has caused a longitudinal wrinkling of the mucous membrane. One of those folds is completely and two are partially shown, j, external, longitudinal layer of the muscular coat ; t, areolar tissue forming the external coat and connecting the pear, the attached ends of the cells becoming clearer and the whole cell diminishing somewhat in size during the process. The nerv(;s of the stomach and intestinal tract form two gan- glionated ])lexuses, the plexus of Auerbach, which lies between the two layers of the muscular coat, and the plexus of Meissner, situ- THE DIGESTIVE ORGANS. 143 atcd in the sulnmicous cout. From these plexuses fibres are dis- tributed to tlic museles 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 lym])hadenoid tissue in the alimentary tract have special Fk:. 122. 1^';^'^ -0 Section of Imman pancreas. (Biihrn anrl Davirtoff.) a, larger duet ; b, beginning of duct ; c, d, acini witli cells belonging to tlic corresponding duct-radicles in their centers; e, acinus, cut just beyond the lumen ; /, interalvcolar 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. - >'^ >f ^*' Section through one of the crypts of the tonsil. (Stohr.) e, stratified epithelium of the gen- eral surface, continued into the cryptt;/, follicles containing germinal foci. Between the follicles is a more diffusely arranged lymphadenoid tissue, s, material within the crypt, composed in jnirt 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 an invasion of the lymphadenoid tissue beneath. We therefore find the tonsils specially prone to such inflammatory THE DIGESTIVE ORGANS. 145 Section through the funilus of a crypt. (Beiida and Guenther's ^Was.) 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- ino; 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 Vjy 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 difi^erent 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 t[ie liver (Fig. 125) will reveal portions of these two trees, cut in various directions witli 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 liepatic vein, in all its ramifications, is separated from the other vessels by the parenchyma of the organ. If we select some part of a section which contains one of the smallest branches of the hepatic vein, and cut across its axis so that its lumen appears round, we shall notice that at about equal distances from it there are sections of two, 146 77//-; IJVKR. 147 three, or four twigs of the compound tree. In these the gall-duet can be identified hv 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 ves.sclf^. 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 liepatic 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 a|>pear 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 jx'ripheries, 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 sej^arated 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 vessels, 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). Vessels and bile-ducts of u lobule of a rabbit's liver in transverse section. (Cadiat.) a, cen- tral vein ; b, b, interlobular veins (branches of the portal vein) ; c, interlobular bile-duct, 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 lieen wholly omitted. Between the int('rl()])ular ea])illaries are rows of epithelial cells, which con.stitute the functional part of the liver, its parenciiyma. 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 THE LIVER. 149 human liver the epithelial eells of the parenchyma form a plexus lying in the meshes of the ea{)illary network of the interlobular vessels. It requires an effort of the imagination to conceive of a third j)lexus 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 gnjoved upon its surface to form half of the tiny canal. The cells themselves have tine 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 clearly seen, appearing as little round or oval spaces at the junction of two Fig. 127. Fig. 128. V Fig. 127.— Perivascular lymphatic of the human liver. (Disse.) c. capillary in longitudinal section; a, lymphatic space between the capillary and row of epithelial cells: 6, wall of the lymphatic space, slightly separated from the liver-cells and drawn a little em- phatically; /, liver-cells; d, 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. (PfeifTer.) 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. 128). 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, wliile 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. 1 29. Portion of hepatic lobule of the rabbit ; cells infiltrated with glycogen. (Barfurth.) The animal had been fed for twentj^-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 di.-solves out of the cells during the ordinarv processes of fixation and hardening preparatory to the preparation of sections, leaving spaces in the cytoplasm, which cau.se it to have a coar.'sely reticulated appearance in cases where the glycogen was abundant. This reticulation would render it impossible to distinguish the minute intracellular bile-passages. Each cell has 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 Tin: LIVER. 151 of opltliolinm. In the hunuui liver this tubular strueture 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 fjlance 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 l)ilo 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. Tlu> blood comes into such close relations with the epithelial cells of the liver that an interchange of soluble substauces 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. CHAPTER 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 uj) 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 papilla? of the kidney and the pelvic calix that embraces it. In some of the lower animals — e. 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 tij^s of the papillse. 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. Ivobe lobule Diagrammatic sketch of a section of the kidney : a, 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 b. 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 Mr.lpighian bodies. The extensions of the cor- tical suVjstance 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 cacli other, and the sulci between them become indistinct or are wholly f)bliterated. 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 tiiix^s, 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 jnramid, and, therefore, nearly perpendicular to the base of tlfe 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 kidnev, "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 cour.se 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; '.',, first convoluted tubule; 4, spiral portion of the first con- voluted tubule in the medullary ray; n, descending limb of Ilenle's tube; 6, Henle's loop; 7, 8, y, ascending limb of Ilenle'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 be.st to complete this general .sketch by con.sidering the course of the blood ve.s.sel.s. As has already been said, the vessels enter the kidney between the calices and pyramids and are di.stributed in branches that lie THE URINARY ORGANS. 157 Fm. 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 I^ranches 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. Fk;. 133. Fig. 13' -Diagram showing the course of the bloodvessels within the kidney. (Ludwig.) a, interlobular artery ; b, interlobular vein ; c, 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; ri. vena stellata: e, artcrix recta.-;/, venifi rectse; g, capillary plexus around the mouths of the excretory ducts. Fig. 133.-Injected glomerulus from the horse. (Kolliker, after Bowman.) a, interlobular artery; a/, afferent vessel; m,m, capillary loops forming the glomerulus; ^, efferent vessel; b, capillary network in the labyrinth and medullary rays. The main artery becomes smaller in giving off these branches, and finallv ends in terminal afferent vessels (Fig. 132). 158 NORMAL HISTOLOGY. Within the Malpighian body the afiPerent 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 ; 6, afferent vessel ; c, capillary springing from afferent vessel ; d, Bowman's capsule, with ei>ithelial 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; o, 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 cai)sule 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 lal>yrinth 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 caj>illa- THE URINARY ORGANS. 159 ries run, for tlu! most i>art, parallel to the renal tnlniles, with com- paratively few transverse anastomosing branches. For this reason they have been called the "vasa recta." They also receive blood from little fvviy-s uiven otf from the arterial arcade. The blood from the intertubnlar ca})illaries 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," " vense rectae," and " venous arcade." Relatively 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- FiG. 135. Fjg. 136. mi Cross-sections of convoluted tubules lined with cells in diflerent 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. tlu'lial cells, which is reflected at that attachment and forms a lining for the inner surface of the capsule to the jioint 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 ditfer.-!, 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 ej)ithelial 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 fi])r()ns tissue. The latter is present 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 a})pear 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, ])ossibly, here and there a "loop" in nearly longitudinal secti(jn, will appear. Among all these sections of the tubules the THE URINARY ORGANS. 161 interstitial tissue with its ca])illaries ami lynipliaties will complete the picture (Figs. lo7 and I'dH). ¥ui. 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 dupt.s) ; b, Henle's loop in tangential section ; c, capillary bloodvessels ; d, lymphatic ; e, descending limb of Henle's tube. Fig. l.'?8.— 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; <;, 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 papillae. 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. .^J- Capillary loop from the glomerulus of the frog. (Xuf^sbaum.) 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 glomerulus, 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 })rcvcntion 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 se>^ '"'wv-^J, '•-C; -S \\.s r-^r Section of liinR of the dog: a, oblique section of a bronchiole ; h. its muscular coat ; c, longi- tudinal section of an infundibnliim, communicating to the right with an alveolar passage (the wall of the latter is torn further to the ""ight) ; rf, one of the alveoli opening into c. The lymphatics arise in the walls of the alveoli and bronehi and pass to the bronchial lymph-glands. The nerves su]i]ilying 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- m(>dullated varieties. The surface of the lung is covered with .serous membrane, a por- tion of the pleura. liittle 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 lun^ of a dog, killed by ether-narcosis. The lung was hyperfcmie 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; rj, surface-aspect of an alveolar wall, showing capillary plexus filled with red blood-corpuscles. chest is expanded througli 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 th(> thoracic walls, but chiefly because of the contraction of the elastic fibres in the alveolar walls. THE RESPIRATORY ORGANS. 175 Because of llicii- presence the lungs retract when the chest is opened. When sections of the hmg are examined under tlie mii-roscope it is dinicnlt, at first, to i(h'ntify the diiferent portions, which are cul in all directions. Tiie smaller bronchi may be recognized by the presence of cartilage in their walls. The bronchioles pos- sess no cartilage, but are surrounded by a l)and of smooth mus- cular tissue, the muscularis mucosse. 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 j)lane of the section and ]>arallel 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 ajjpear 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 " trabeculse," penetrate into the substance of the organ, M^iere they branch, and the branches join each other to form a coarse meshwork occupied by the parenchyma of the organ, the '' pulp." The bloodvessels of the spleen enter at the hilum and pass into the large trabeculse, which start from the capsule at that point and enclose the vessels until they divide into small branches. The vessels then leave the trabeculse 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 tlieir 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 tlie 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 ])rocesses, in the meshes of wliich there are red blood-corpuscles, leucocytes in greater number than nonually present in the blood, and free amoeboid cells consid- eral)ly larger than leucocytes, called the " splenic cells." 176 THE SPLEEN. 177 Tlic advcutitiii of the ai'tcrics f()iiUiin.sconsidc'r:il)l(' 1\ iiipliMdcimid tissue, wliitli after tlic exit of the vessels from the trabeculse is Fig. 151. 4^ ;'•• Section from the spleen of tlie cat. (Bannvvarth.) Termination of an arterial capillary in the i»uli>. expanded at intervals to form spherical bodies, about 1 mm. in diam- eter, called the " Malpighian bodies " or " corpuscles." These are Fig. 152. • • V • ^ Section from the spleen of the lat. (Kannwartli.) Beginning of a capillary venous radicle. like little lymph-follicles, through which tlie artery takes its course. The reticuhim in these Malpighian corpu.-^cles is scanty and incon- 12 178 NORMAL HISTOLOGY. spicuous near their centres, so that the lymphoid cells it contains ai)pear densely crowded ; but toward their peripheries the reticulum is more pronounced and tlie 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. (KoUiker.) A, capsule ; 6, b, trabeculee ; c, e, Malpighian bodies (lymph-follicles), traversed by arterial twigs. In the follicle to the left, part of the arterial twig is seen in longitudinal section ; in that to the right, it appears in cross- section to the right of the centre of the follicle, d, arterial branches ; e, splenic pulp. The section is taken from an injected spleen. The relations between the spleen and the blood flowing through it appear to be very similar to those between the lymphatic glands and the lymph passing through them. It seems to act as a species of filter, in which foreign particles or damaged red blood-corpu.scle& are arrested and destroyed. In many infectious diseases the splenic pulp is increased in amount and highly charged with granules of pigment that appear to be derived from the coloring-matter of the blood. This is notably the case in malaria, in which the red cor- puscles are destroyed by the plasraodium occasioning the disease. AVhen bacteria gain access to the blood they are apt to be especially abundant in the splenic pulp, and it is said that monkeys, which are normally immune against relapsing fever, may acquire the dis- ease if the spleen be removed before inoculation with the spirillum THE SPLEEN. 179 Nvliic-li is tlic ciuisc of tliut disease. These observations all tend to confirm the view that (he I'mictidn oi' tiic sph;en is to assist in main- taining the fimetional integrity of the l)h)od. The ]ympha(h-noid tissue within tlie spleen also enriches the blood with an additional number of leucocytes. CHAPTER XV. THE DUCTLESS GLANDS. The organs included in this group possess, at some stage of their development or in the adult, a structure analogous to that of the secreting glands. Those which retain this structure after complete development diifer from the other glandular organs in being devoid of ducts, through which the materials elaborated by their paren- chyma could be discharged. Of these organs the thyroid is the most striking example. Other members of this group, notably the thy- mus, become greatly modified as development advances, and after a Fig. 154. Section of human thyroid gland : a, alveolus filled with colloid ; h, alveolus containing a serous fluid ; c, interalveolar areolar tissue; d, tangential section of an alveolus, giving a superficial view of the epithelial cells. while retain mere vestiges of their original epithelial character; the chief Ijulk of the organ being composed of lymphadenoid tissue. The following organs and structures will be considered as belong- ing to the general group of ductless glands : the thyroid gland, the ISO THE DUCTLESS GLANDS. 181 parathyroids, the adrenal bodies, the pituitary body, the thymus, and the carotid and coccygeal bodies. 1. The Thyroid Gland (Fi^;. 154). — This consists of a number of alveoli or closed vesicles, lined with cubical epithelial cells ar- ranged in a single layer upon the delicate, vascularized areolar tissue which forms their walls and separates the neighboring alveoli from each other. This fibrous tissue is more abundant in places, where it serves to divide the gland into a number of imperfectly defined lobes. At the periphery of the organ its connective tissue becomes continuous with a thin but moderately dense fibrous capsule. The individual alveoli differ both in respect to their size and their contents. Many are more or less completely filled with a nearly homogeneous, glairy substance, of a slight yellowish tint, called "colloid," while others appear to be occupied by a serous fluid. Fig. 155. Fig. 156. Sections of thyroid gland. (Schmid.) Fig. 155.— From a dog : a, colloid or secreting cells ; b, reserve cells (these differ only in their states of activity) ; c, cells containing less colloid than a. Fig. 156.— From a cat : o, daughter-cells arising from the division of an epithelial cell. The elaboration of this colloid material seems to be the function of the organ, though it may have other less obvious duties. The cells lining the alveoli may be divided into two classes, which differ in appearance (Fig. 155) : first, those engaged in the production of colloid, secreting cells ; and, second, those in which no colloid is present, and which are regarded as reserve cells. The latter are capable of multiplication, thereby replacing such of 182 NORMAL HISTOLOGY. the secreting cells as may be destroyed (Fig. 156). The colloid material is produced within the cytoplasm of the secreting cells, Fig. 157. Section from thyroid of dog, illustrating the egress ol colloid from the alveoli. (Bozzi.) a, epithelial cells lining the alveolus, seen in section. The internal ends of similar cells are seen in superficial aspect below, b, colloid within the alveolus ; c, exit of colloid between two epithelial cells ; e, lymphatic vessel ; d, end of a colloid or secreting cell in the epithelial lining of the alveolus. whence it is either expelled into the lumen of the alveolus, or the whole cell becomes detached from the alveolar wall and suffers col- FiG. 158. Section from thyroid of dog, illustrating the egress of colloid from tlie alveoli. (Bozzi.) a epithelial lining of the alve(jlus ; b, colloid ; c, escape of colloid through a defect in the wall occasioned tjy the colloid mctamorpliosis of some of the epithelial cells, the nuclei of which are discernible within the colloid near c. loid degeneration, with destruction of the nucleus, Avithin the alveolar cavity. THE DUCTLESS GLANDS. 183 The colloid material sLib.seqiuiitly Hiids its way into the general circulation, eitiaT by passing botwciii tlic intact cells of the alveolus (Fig. 157), or after a passage has been prepared for it through altera- tions in certain of tiiose cells (Fig. lo, 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 lymphadenoid 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 imbri- 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 groujis or islets of epithe- lial cells, surrounded \)y fibrous tissue from which numerous capil- TIJK DUCTLESS GLANDS. 195 lary bloodvessels are distributed in elose 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, j)robal)ly of epithelial nature, closely applied to the walls of capillary Idoodvessels and surrounded by fibrous tissue. Its function- and mode of origin are both unknown (Fig. 172j. 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, (.\rloing.) n, horny layer of the epidermis ; b, rete mucosum ; c, .surface of the corium ; d, sebaceous pland ; c, areolar tissue of the corium;/, hair-shaft within the hair-follicle; g, lobule 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 loo.sely arranged in its deeper portions, where it becomes continuous with the subcutaneous areolar tissue, and contains 196 THE SKIN. 197 a variable amount of Hit, but more ecjmpaetly disposed in the super- ficial portions, where it comes in contact with the epidermis, into which it projects in the form of pa})illie. Some of these papillfe contain loops of capillary bloodvessels, while others arc occuj)ied in their centres by peculiar nerve-endings, called " tactile corpus- cles." In some situations, notably upon the palms and soles, the papillffi of the corium are arrantred 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 Vertical section of the epidermis of the finger. (Ranvier.) a, stratum corneum, or horny layer; 6, stratum lucidum ; c, stratum granulosum; (/, 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, -svhere 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 niunber 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 Avhich gradually enlarge, becoming rich in cytoplasm, and arc connected with each other by minute cytoplas- mic " prickles," between which there is a space aifording 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," widiiii 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 defeneration, so that after a while the Avhole 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. AVithin 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 oj)ithelial 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. Till': sKiy. 199 The sebaceous glands can best be described in connection witli the hairs and tlicir follicles. The bulbous attachment, or " root," of the hair, and the adjacent ])ortion of its shaft, are contained in an invafj;! nation of the corium and e[)iderinis, called the " hair-follicle" (Fig. 17.j,/). 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 lM(i. 176. Section through the coiled end of a sweat-gland. (Klein.) a, b, 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 occu])ied by the hair. This layer of epithelium is reflected upon the surface of the papilla, where 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 tiie 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. . — _/. Hair-follicle from the human scalp. (Mertsching.) Longitudinal axial section through the fundus: a, h, 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 ; n', 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 ; r/, 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 SKIN. 201 make up tlic oliiof nuijfs of the liair-.-^liatt. In the centre of thir- 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, <1) are sacculations in the cerium 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. t/ I ■ ■ . V^ ^ Hair-follicle from the human scalp. (Mertsching.) Cross-section from middle third of the follicle: 6, lonEritndinal and cncirclin.s: layers of the fibrous coat; e, hyaline layer, formed of an outer faintly fiVirillated and an inner more homogeneous lamina, cf ; e, outer root-sheath, continuous with rete mucosum of epidermis ;/, Henle's sheath; 17, Huxley's layer ; h, cuticle of root-sheath ; t, cuticle of hair ; /, 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. Sebaceous gland from the evtenial auditory canal. (Benda and Guenther's Atlas.) a, epi- thelium continuous with that Imma; the haii -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 frctns. (Ernst.) a, matrix of the nail formed by an invagination of tlie rete niucosum. Near the p(jint indicated by the letter the epitliolial cells have begun to change into keratoid material, b, loosened scales of the surface of the nail ; c, remains of the fiotal 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). Till': SKIN. 203 The skill contuiii.s littlo muscular bands, the urrectores pili (Fig. 173, 7/j/*), composed of smooth muscuhir fibres, which are attached to tiic fibrous coat of the hair-follicles near their deep extremities and to the suj)erficial layer of the corium on the side of the fol- licle toward which tiie liair leans. The action of these mus- cles is to cause the hair to assume a more vertical position, and to raise it and tiie 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 l)y the moisture proceeding from the sweat-glands, the " insensible perspi- ration," The skin also })lays a })rominent 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 arrcctores pili shorten, occasioning the production of a roughness of the skin, goose-flesh, and probably also a discharge of se- biuTi, which reduce the evaj)oration 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. Hair-rudiment from an embryo of six weeks. (Kolliker.) a, horny layer of epidermis ; b, Malpighian layer, rete mucosum ; i, limiting membrane ; in, vi, 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 Fig. 182. Section of developing tooth. From embryo of sheep. (Bohm and Davidoff.) a, epi- thelium of the gum; b, its deepest layer; c, sui^erficial cells of the enamel-pulp; d, enamel-pulp formed of modified epithelial cells ; s, cells of the enamel-pulp destined to produce the enamel (" adamantoblasts ") ; p, dental papilla. underlying connective tissues (Fig. 181). The sebaceous glands ari.se as oifshoots from these cellular masses. THE SKIN. 205 The Teeth. — The (levelopnieiit of the teeth presents close anal- ogies to that of tiic hairs. They also first appear as little masses of cells, growing into the connective tissues of the alveolar proc- esses from the stratified cipitheliinn covering them. Into the bases of these masses connective-tissue })apilhe are develoj)ecl, which eventually become ditt'erentiated into the pulp of the tooth-cavities. The e])ithelial cells which immediately surround these papilhe be- come elongated to a columnar form and then become converted Sr- ■Sr Section of developing tooth. From embryo of nibbit. (Freund.) cp, epithelium of gum; «/i, epithelial cells forming outer layer of the enamel-pulp of the temporary tooth ; L, sim- ilar layer belonging to the rudiment of the permanent tooth ; ^>•, euamel-pulp; p, dental pulp of the tooth-eavity ; d, dentin; v, bloodvessels; B, rudiment of second or permanent tooth ; a, embryonic connective tissue of the alveolar process. into or elaborate the tissue of the enamel. The superficial cells of the papillse likewise elongate and produce the dentin. The cement which constitutes the outer layer of the root of the tooth is bone, and is developed from the foetal connective tissue in that region (Figs. 182 and 183). Only a brief descrij)tion of the structures entering into the forma- tion of the fully developed tooth can be given here. For a more detailed account of them the student is referred to special works on the .-subject. 206 NORMAL HISTOLOGY. Fig. 184. The centre of the tooth is hollow, and the cavity opens by a small orifice at the tip of the root. This cavity is filled with a highly vascular delicate areolar tissue, richly supplied with nerves. Where this pulp is in contact with the tooth its outer layer is made up of modified connective-tissue cells, odontoblasts, which are capable of elaborating den- tin. The body of the tooth is com- posed of dentin. This contains minute canals, analogous to the canaliculi in bone, but much longer. They extend from the pulp-cavity nearly, if not quite, to the outer boundary of the dentin, and, toward their terminations, give off Ijranches. These canals are occupied by long fibrous processes of the odonto- blasts already mentioned. The crown of the tooth, down to its neck, is covered with enamel. This is a tissue derived from epithelium, and is composed of long, prismatic ele- ments extending from the surface of the tooth to the dentin. These prisms have a polygonal cross-section and are held together by a hard cement-sub- stance. They are not perfectly recti- linear, but pursue a wavy course, being disposed in laminae or bundles, in which the prisms have not quite the same direction. The root of the tooth, below the point where the enamel ends, is covered with cement, which has the structure of ordinary bone, but is usually devoid of Haversian canals (Fig. 184). Axial section of a human tooth having but one root: a, enamel; b, dentin; c, cement. CHAPTER XVII. TUB REPRODUCTIVE ORGANS. I. IN THE FEMALE. The female reproductive organs are : ( 1) the ovarv, in which the egg is produced ; (2) the Fallopian tube, through which it is con- veyed to (3) the uterus, where it develops into the fcjetus, and from which the child at maturity passes through (4) the vagina and (5) external genitals into the external world. 1. The Ovary (Fig. 185). — The free surface of the ovary is cov- ered with a single layer of columnar epithelium, called the "germinal epithelium." Beneath this the substance of the organ is composed of a vascularized fibrous tissue, the " stroma," which is slightly dif- ferent in the details of its structure in different parts of the organ. Immediately beneath the germinal epithelium it is slightly richer in intercellular substance than in the suljjacent parts, so that the organ appears to have a proper fibrous coat. This coat is not dis- tinct, however, and gradually passes into a highly cellular form of fibrous tissue, in which the sj)indle-shaped cells are separated by only a small amount of a delicate fibrous intercellular substance. Toward the hilum of the ovary this connective tissue passes into a more distinctly fibrous tissue, containing a larger amount of inter- cellular substance and cells that are less prominent. In this portion of the stroma the larger vessels supplying the organ are situated, and from it they send smaller branches throughout the stroma of the organ. Within the more cellular regions of the stroma are the structures known as the Graafian follicles, each of which contains an ovum. In order to understand the structure of these Graafian follicles it will be well to trace the history of their development. The Graafian follicles and ova are derived during foetal life from the germinal epithelium covering the ovary. From this layer of cells little columns of epithelium make their way into the stroma, where they become broken up into small isolated groups, in each of which one of the cells develops into an ovum. Avhile the rest con- tribute to the formation of the Graafian follicle. This mode of origin 207 208 NORMAL HISTOLOGY. may serve to explain the fact that the younger Graafian follicles are nwst abundant in the peripheral portion of the stroma. At first the Graafian follicle consists of a large central cell, the ovum, c f Fig. 185. c Section from the ovary of an adult bitch. (Waldeyer.) a, germinal epithelium ; h, b, columns of germinal epithelium within the stroma ; r, c. small follicles ; d, much more advanced follicle ; e, discus proligerus and ovum ; /, second ovum in same follicle (a rare occur- rence); g, fibrous coat of the follicle; h, basement-membrane; i, membrana granulosa of epithelium; d, liquor foUiculi; k, old follicle from which the ovum has been dis- charged ; I, bloodvessels ; m, m, sections of the parovarium ; y, ingrowth from the ger- minal epithelium; z, transition from the germinal epithelium to the peritoneal endo- thelium. surrounded by an envelope of somewhat flattened epithelial cells, which are in direct contact externally with the unmodified, highly cellular tissue of the stroma (Fig. 186). As the Graafian follicle develops, its position in the ovary becomes more central, and the cells around the ovum lose their flattened shape and divide, forming a double layer of cubical or columnar cells. These two layers then become separated by a clear fluid, 77//; REPRODUCTIVI-: ORGANS. 209 the li(|iinr tolliculi, so that the outer layer forms the wall of a sac, while the inner layer remains as a close investment of the ovimi. The cells of these two layers multij)ly : those siirroini(lintn>iiia iu ovary of adult sow. i I'latu., T Ik- o\ um occupies the centre of the follicle, appearinsras a very large cell with a large vesicular nucleus ("germinal vesicle"), within which is a large nucleolus ("germinal spot"), exceeding in size the whole nucleus of the surrounding epithelial cells of the follicle. The cells of the stroma are arranged about the follicle as though to form the fibrous coat of the latter. In the lower portion of the figure are three large cytoplasmic cells, containing globules of fat and granules of pigment. These cells are analogous to those found in the interstitial tissue of the testis. The epithelium of the Graafian follicle, and the ovum, also contain globules of fat of various sizes, stained black by the osmic acid used in the preparation of the specimen. contribute a clear basement-membrane and a fibrous envelope, the " membrana propria," to the structure of the follicle. The follicle now eulartics, as the result of an increa.^e in the amount of the H([iior folliculi, eventually approaches the surface of the ovary at some ])oint, and then ruptures, discharging the ovum. After the rupture of the Graafian follicle and the escape of its contents a slight hemorrhage usually takes place into its cavity, which then ai)pears filled with remains of the liquor fol- liculi mixed with coagulated blood. Into this, granulations ^ now ' See Chapter XXIV. 14 210 NORMAL HISTOLOGY. develop from tlie fibrous wall, replacing the clot and eventually producing a scar. This process is much more rapid in case the ovum is not impregnated (corpus hsemorrhagicum) than when im- pregnation has taken place. In the latter case 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 yellowish zone is the remainder of the clot, and about its periphery an envelope of fibrous tissue, which is usually irregular in contour. The corpus luteum finally becomes a mass of cicatricial tissue of greater size than that resulting from a corpus hsemorrhagicum (corpus album) (Figs. 187 and 188). Fig. 187. ■l-e thi e Section from rabbit's ovary, illustrating the formation of the corpus luteum. (Sobotta.) Recently rui)tured Graafian follicle, ke, 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 fiibrous 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 the mcmbrana granulosa. Within this are the viscid remains of the liquor folliculi, containing a few red blood-corpuscles and some epithelial cells detached from the mem- brana granulosa, W, red blood-corpuscles. This section was prepared from an ovary about twenty-four hours after coitus, 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 Via. 188. Section of young corpus lutcuni, four days after coitus. The prolii'ijiatiu!^ connective tissue has nearly filled the cavity of the follicle, only a small mass of tibrin remaining in its centre. The young connective tissue is highly vascularized, the blood in some of the capillaries being represented, r/. ke, germinal epithelium. Below is the margin of a Graafian follicle, with its membrana granulosa. iniiseular coat are situated. This is followed ))y an internal mus- cular coat of encircling bundles of smooth muscular tissue, inside of which is the submucous coat of areolar tissue, containing a few scattered ganglion-cells. The raucous membrane consists of a highly cellular connective tissue covered with ciliated columnar epithelium. During life these cilia propel toward the uterine cavity substances coming into con- tact with them. Toward and at the fimbriated extremity of the tube the raucous membrane is thrown into deep longitudinal folds, upon which are numerous secondary and tertiary folds, but further toward the uterus these folds give place to branching villous pro- jections into the luraen (Fig. 189). Toward the uterine end of the tube these complicated folds and villi disappear and the lumen of the tube becomes round or stellate. 3. The Uterus. — The external surface of the uterus, throughout most of its extent, is covered by a reflection of the peritoneum. Beneath this are three distinct coats of smooth muscular tissue, the 212 NORMAL HISTOLOGY. outer two in close contact with each other ; the two inner separated by a thin layer of areolar fibrous tissue, supporting large blood- vessels. This separation of the innermost layer from the middle layer leads to the inference that the former is analogous to the mus- cularis mucosae found in other hollow viscera, although in the uterus it forms the chief mass of the muscular tissue of the organ. The outer layer is made up of bundles of fibres that have a general longitudinal position ; the two inner layers have a general circular Fig. 189. Transverse section of the Fallopian tnhe near its free end. (Orthmann.) Numerous branch- ing villous projections of the wall, covered by ciliated columnar epitlielium, extend into the lumen. The open spaces in these villous projections are sections of the bloodvessels. dis])osition of their bundles, though the latter interlace with each other in various directions within the muscularis mucosae, leaving masses of areolar tissue containing the larger bloodvessels between them. Covering the surface of the muscularis muco.sse is a highly cellu- lar connective tissue, not unlike granulation-tissue in appearance, except th;it it is less richly supplied with bloodvessels. It is composed of round and fusiform cells, lying in a small amount of intercellular Till-: IIFA'RODUCTIVE OIKIANS. 213 suhstaiico, in wliitili fibres ciin be distinguished only with (Jilheulty. The siirfSice niucosu containing vascular trunks ; e, muscular coat. Outside of the latter is the ill-dcfincd fibrous coat, not represented in the ligure. lium. Outside of this coat is one of smooth muscular tissue, which is not clearly divisible into layers, but in whi(^]i the inner fibres are chiefly circular, forming an imperfectly defined muscularis mucosae, while the outer have a longitudinal direction, and may be regarded as the true muscular coat of the vagina. Outside of the muscular THE RKriiODUCTIVE ORGANS. 217 coat is a layer of areolar tissue connecting the vagina with the nciglihoriiig parts, except at its |)ost(!rior and u[)])er part, where it is covered with a serous membrane, forming part of the peritoneimi. 5. The External Genitals. — Tlu; iiymen is a fold of the mucous membrane, and ((tiisists of fibi'ous tissue with a covering of strati- fied epithclHun. The same general structure obtains also in the labia minora, j)r('puce, and labia majora ; but the labia miintra and ])re])uce are destitute of fat, wiiile the labia majora contain consideraide adipose tissue. All three organs are sup})lied with sebaceous glands, which are numerous beneath the prepuce and are associated with hairs only on the labia majora. The latter also contain fibres of smooth mus- cular tissue, corresponding to the analogous dartos of the scrotum. The bulbi vestibuli, crura of the clitoris, and the body and glans of that organ are comj)osed of erectile tissue. The glands of Bartholin are compound racemose glands, in which the alveoli are lined with a columnar epithelium resembling in structure that of the mucous glands in other ])arts of the body. The epithelium lining their ducts is of the cubical variety. The parovarium is a remnant of the Wolffian body of the foetus, consisting of a series of blind tubules lined with e|)ithelium (Fig. 185). It is situated between the Fallopian tube and the ovary. The remains of the Wolffian duct and of the duct of Miiller, having a sim- ilar structure to the tubules of the parovarium, are sometimes per- sistent, the one connected with the parovarium, the other with the extremity of the Fallopian tube. These structures are of interest because tumors occasionally arise from them. The Maturation of the Ovum. — Before the ovarian ovum is ready for fertilization it must undergo two divisions, during which the amount of chromatin left in the mature G^,g is reduced one-half. The first division results in the formation of two cells, which differ enormously in the amount of cytoplasm they possess, but which have equal shares of the chromatin in the original nucleus. The smaller of these two cells is known as the " first polar body." After its separation from the larger cell both cells divide again, without an intermediate growth of the chromatin. In this second division of the larger cell the two resulting cells are again very unequal in size, the smaller being the " second polar body." The first jiolar body having also divided, there result from these successive divis- ions one mature egg and three polar bodies, each with only half as many chromosomes in its nucleus as are commonly found in the 218 NORMAL HISTOLOGY. general or " somatic " cells of the body (Fig. 193). The polar bodies perish, as does also the ovum, unless fertilized by the introduction of a spermatozoon. The latter, as we shall see, also contains half the number of chromosomes contained in the somatic cells ; so that Fig. 193. Maturing ovum of physa (fresh-water snail). (Kostanecki and Wierzejski.) Above are the two small cells resulting from the division of the first polar body. Below is the ovum, the nucleus of which is dividing to form the second polar body. Near the centre of the ovum is the nucleus of the spermatozoon, just above which is its (divided) centrosome with surrounding radiations in the cytoplasm. When the second polar body has been formed the chromosomes remaining in the ovum will be ready to participate with those of the spermatozoon in the further development of the then fertilized egg. after its entrance into the mature ovum the latter acquires its full complement of chromosomes and is ready for development. The Mammary Gland. — Each mamma consists of a group of about twenty similar compound racemose glands, 0])ening by distinct orifices at the tip of the nipple, and separated and enclosed by fibrous tissue, in which there is a variable amount of fat. At the edges of the mamma this fibrous stroma becomes continuous with the tissues of the superficial fascia in which the breast is situated. Each of tlie glands entering into the composition of the breast possesses a single main duct, the " galactiferous duct," which is lined with columnar epithelium, except near its orifice, where the strati- THE RKVRODUCTIVE ORGANS. 219 fiod o])itlu'liiim of tlio opidcrmis extends for a short distance into its liiMK'M. A little below the base of the ni])j)le the duet presents a fusiform dilatation, called the " ampulla," which serves as a reser- voir for the comparatively small amount of milk secreted in the intervals hi-tween nursings. The main duct branches in its course from the ni]»ple into the deeper portions of the gland, and these branches give off twigs, which terminate in the alveoli of the gland. The columnar epithe- lium lining the main duct gradually passes into a cubical variety in the branches, and this becomes continuous with the epithelial lining of the alveoli. The terminal branches of the ducts are short, so that the alveoli opening into them lie close together and are col- lectively known as a "lobule" of the gland. These lobules are, in turn, grouped into lobes, each of which corresponds to one of the main ducts of the breast. The individual alveoli and the lobules are surrounded by fibrous tissue, which may be subdivided into an intralobular and an inter- lobular portion, the latter more abundant than the former. This fibrous tissue supports the vessels and nerves supplied to the gland. The character of the epithelium lining the alveoli varies with the functional activity of the gland. Before puberty the secreting acini are only slightly, if at all, developed, the mamma consisting of a little fibrous tissue and the ducts of the gland, which possess slightly enlarged extremities. When the gland has become fully developed, at or about puberty, the epithelial cells lining the acini are small and granular and nearly fill the diminutive lumina. The fibrous stroma is, at this period, abundant and makes np the chief bulk of the breast. When the gland assumes functional activity the cells enlarge and multiply (Fig. 194), and the lumina of the acini become dis- tinct and filled with a serous fluid. Into this fluid a few fat-globules are discharged from the epithelial lining, forming an imperfect milk, very poor in cream and differing in the proportions of the dissolved constituents from the milk that is produced after the function of the gland is fully established. This secretion is called " colostrum." Besides the scant supply of fat-globules which it contains, it is fur- ther characterized by the presence of so-called colostrum-c(»rpuscles. These are leucocytes which have wandered into the acini of the gland from the bloodvessels in the interstitial tissue, and have taken some of the fat-globules of the secretion into their cytoplasm. This 220 NORMAL HISTOLOGY. process results iu an enlargement of the leucocyte, and, in extreme cases, to an obscuring of the nucleus and cytoplasm by fat-globules, so that the whole appears as though composed of an agglutination of numerous drops of fat (Fig. 195), As the functional activity of the gland matures the epithelial F:g. 194. Fig. 195. vt) 0 Fig. 191.— Dividing epithelial cells from the mammary gland of the guinea-pig. (Michaelis.) The figure represents the proliferation of the cells by the indirect mode before lactation has been established— -i. e., during the maturation of the gland. Fig. 195. — Colostrum-corpuscles and leucocytes from the colostrum of a guinea-pig. (Michaelis.) cells lining its acini produce drops of fat in the cytoplasm bor- dering on the lumen, and these are subsequently discharged into the lumen, forming the fat or cream of the milk. The casein of the milk appears to be produced in the following manner : it has been observed that during lactation the nuclei of some of the cells present changes in form that lead to the inference that they undergo division by the direct mode — i. c, without passing through the phases of karyokinesis. It thus happens that some of the epi- thelial cells contain two nuclei. These cells, after a while, project into the lumen of the acinus, the two nuclei lying in a line perpen- dicular to its wall. It is supposed that the nuclei nearest the lumen become detached, together with some of the cytoplasm, and that the chemical constituents of the nucleus and cytoplasm enter into the formation of the casein. Such free nuclei have been observed in the lumina of the acini, and it is known that the chromatin which they contain disintegrates and eventually disappears (chromolysis), so that it is not found in the secreted milk. It is probable that the other constituents of the nucleus likewise undergo chemical changes (karyolysis) (Fig. 196). THE REPRODUCriVI-: ORCAXS. 221 When lactation is suspoiult'd tlie breast at lirst secretes a Hiiid in every way resembling colostrum, and eventually returns to the dor- mant state, in which the cells are again small and granular and the stroma is relatively abundant. As the glandular {)ortion ot" the breast enlarges during lactation, the whole breast becomes increased in size, but this increase is not proportional to the develo[)UU'nt of the alveoli, for the stroma is reduced in amount, so that tlu; lol)ules of the gland arc closer to each other. After the period of lactation is ])asscd the alveoli return almost to their original size, but the stroma is not repro- FiG. 196. Section from the mammary gland of a gulnea-pi-.: rturinsx lactation. (Miehaelis.) The fip:ure represents sections of two acini and the margin of a third, separated by vascularized areolar tissue, a, fat-globule, separated from the lumen by a mere film of cytoplasm ; b, projecting cell with two nuclei : c, two nuclei which appear to have been produced by constriction of a single pre-existent nucleus. duced in fibrous form, but its place is taken by adipose tissue, the amount of which depends upon the individual, being great in those that are fat, and slight in those that are lean. In the latter, therefore, the brea-^^t becomes soft and pendulous after lactation has ceased. It is important to bear the above changes in the normal gland in mind when examining the mamma for evidences of a tumor. When, for example, the stroma is abundant and the glandidar structures undeveloped, as is the case before puberty, sections of the gland mav be mistaken for those of a mammarv fibroma. 222 NORMAL HISTOLOGY. The nipple is composed of fibrous tissue, with a considerable admixture of elastic fibres, in which there are scattered bundles of smooth muscular tissue lying parallel to the axis of the nipple. A circular bundle of the same tissue is found at the base of the nipple, and by its compression on the bloodvessels may be the cause of the erection of the nipple. The skin at the base of the nipple and in the areola surrounding it contains large sebaceous glands. The mammary gland in the male is functionless, and, while it contains the same structures as in the female, it remains in a com- paratively undeveloped condition. II. IN THE MALE. The male organs of generation include the penis, prostate, vesic- ulse seminales, vasa deferentia, epididymis, and testes, together with certain accessory glands. 1. The Penis. — This is formed by three parallel structures : the corpora cavernosa, lying side by side and partially blending in the median line, and the corpus spongiosum, situated beneath their line of junction and containing the urethra. At its anterior end the corpus spongiosum expands about the ends of the corpora cavernosa to form the glans penis. These three bodies, except over the glans, are firmly held together by fibrous tissue, which is condensed at their surfaces to form compact sheaths or external coats enveloping the erectile tissue of which each is composed. The sheaths of the corpora cavernosa are incomplete where they are in contact, permit- ting the erectile tissue to blend in the median line. This inter- communication is freer toward the anterior end of the penis than near its root, where the corpora cavernosa are more distinctly sepa- rated, preparatory to their divergence to form the crura. The sheaths of the corpora cavernosa are composed of fibrous tissue containing an abundance of elastic fibres. From its inner surface each sheath gives off a number of fibrous bands, called " trabecule," which divide and anastomose with each other, forming the chief constituent of the erectile tissue. Within these trabeculse are numerous bundles of smooth muscular tissue. The erectile tissue is made u]) of these trabeculae, which give it a spongy character and are covered with endothelial cells, converting the spaces between them into cavernous venous channels. These become engorged with l)lood during erection. The vessels supplying this blood are situated in the trabecular, and give off capillary branches, which 77//; REPRODUCTrVE ORGANS. 223 Fig. 197. open into the iulLiti'ubccular spaces, ili>cliarj[^iiirane covered with columnar epithelium, resting upon areolai* fibrous tissue. (Jiitside of this is a muscular coat containing internal circular and external "longi- tudinal fibres, and surrounded by an ill-defined fibrous coat that passes into the general areolar tissue of the region. The seminal vesicles sometimes contain semen, for which they may serve as a temporary reservoir, but they also secrete a fluid that is mixed with the semen at the time of ejaculation. 4. The Vasa Deferentia. — The vas deferens of each side resembles the seminal vesicle in structure. It is lined with columnar epi- thelium, beneath which is a layer of areolar fil>rous tissue, resting upon the muscular coat. This is surrounded by fibrous tissue, becoming areolar as it blends with that of the neighboring parts. The muscular coat is thicker than that of the seminal vesicle, and is divisible into an inner layer of circular and an outer layer of longitudinal fibres. The mucous membrane, like that of the sem- inal vesicle, is thrown into folds, which are longitudinal throughout most of the course of the vas deferens, but are irregular in the sacculated distal portions of the tube, giving the surface a reticu- lated or alveolar appearance. 5. The Epididymis. — The vas deferens of each side becomes con- tinuous with the canal of the epididymis, which is an enormously long tube, twenty feet, so convoluted and packed together as to occupy but little space. It is lined throughout with coliunnar epi- thelium, continuous with that of the vas deferens ; but, except for a short distance from the junction with the vas, the cells possess cilia of considerable length, which induce currents toward the vas deferens. The muscular coat of the latter is continued in the epididymis, but is very thin. Opening into the canal of the epididymis are the vasa efferentia of the testis. 6. The Testis. — The testis is a compound tubular gland, of which the secretion contains the spermatozoa. The latter are derived from certain of the cells lining the tubules, and contain within their 15 226 NORMAL HISTOLOGY. structure a definite amount of chromatin and a centrosome. During the fertilization of the ovum this chromatin unites with a similar amount present in the egg-cell, and thus forms a complete cell, the nucleus of which contains equal amounts of chromatin from the male and female parents of the future offspring. We have seen (Chapter I.) that the nuclei of the cells throughout the body break up, during karyokinesis, into a definite and constant number of fragments, called " chromosomes," which split during metakinesis ; one-half of each chromosome going to each of the daughter-nuclei. These chromosome-halves form a reticulum within the daughter- nuclei, and while in that form the chromatin appears to increase in amount, so that by the time the cell divides again the full supply of chromatin is present in its nucleus. During the two cell-divis- ions which immediately precede and result in the formation of the spermatozoa and the matured egg this growth of the chromatin does not take place, and, as we shall presently see, each spermato- zoon or matured ovum contains but half of the chromosomes that are normally present in the somatic or general cells of the body. This " reduction of the chromatin " has been a matter of much study within the last few years, because of its probable bearing upon the problems of heredity. The fact of its occurrence is strongly con- firmatory of the idea that the chromatin is the carrier of hereditary characteristics, the fertilized ovum receiving equal shares from both parents. The tubular glands of the testis are enclosed in a strong fibrous cap- sule, made up of interlacing bands of fibrous tissue. This becomes con- tinuous, behind, with a mass of areolar tissue containing the vascular supply of the organ and the epididymis, with the vasa efferentia open- ing into it. The fibrous capsule is called the " tunica albuginea." It is covered, except posteriorly, by the visceral portion of a serous mem- brane, the " tunica vaginalis." From the inner surface of the capsule numerous bands and strands of fibrous tissue, trabecule, traverse the glandular part of the organ, imperfectly dividing it into lobes, each of which contains several of the glandular or seminiferous tubes. Upon the surfaces of the trabeculse and upon the inner surface of the capsule the dense fibrous tissue of those structures passes into a delicate areolar tissue, which gives support to the numerous small bloodvessels and abundant lymphatics distributed within the organ. This vascular areolar tissue also penetrates between the seminiferous tubules, giving them support. In this region the THE REPRODUCTIVE ORGANS. 227 interstitial tissue just mentioned contains large cytoplasmic cells of connective-tissue origin, which frequently contain globules of fat or granules of pigment, and in many instances, in man, have been observed to contain crystalloids of proteid nature. It has been surmised that these cells may serve for the storage of nutri- ment required by the active proliferation of the cells that produce the spermatozoa within the seminiferous tubes (Fig. 200). Fig. 200. .■1® ^. "^S^te 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 laver, 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. (Etaner.) /.basal plates of the sustentacular cells (cells of Sertoli), each containing a large vesicular nucleus, poor in chromatin, and a distinct nucleolus of considerable size; ic, spermato- gonia resting upon the basal plates of the cells of Sertoli. Only a few of the spermato- gonia are represented. Fig. 202. Fig. 203. h 13 s29 h 14 / Sections from the testis of the rat, illustrating spermatogenesis. (Ebner.) Figs. 202-213.— MI, spermatogonia ; /, sustentacular cells, or cells of Sertoli; h, spermatocytes; «, spermatids ; .sp, spermatids becoming trausfdrmed into spermatozoa: w\ to wlfl traces the history of the spermatogonia from the resting condition to that in which they have grown to become primary spermatocytes. During tliis process they move from the parietal layer into that covering" it. /dl, a recently formed .^^iiorniatdcyte ; liVl to lr3K growth of the spermatocyte; /i21, beginning of the division to form secondary spermatocytes; Icl2, its end; /i23, secondary spermatocyte, with chronuitin in open siiirom: /(24, division of the secondary spermatocyte to form two spermatids; .s2.'), recently formed spermatid : .«26 to 829, growth of the spermatid. (By this time the preceding croj' of spermatozoa is fully developed and has Viciii diseharged into the lumen of the seminiferous tube.) .s;!0 and «:}1, beginning transforiii;ition of the spermatids into sjiermatozoa. Tlieir cytoplasm blend.s with that of I he sustentacular cell. .'-p32 to .>.7;:!!i, stages in the dillerentiation of the spermatozoa; W, completi'd spermatozoon readv to yniss into tlie lumen of the tube. wl (Fig. 212) and ■»'// (Fig. 21:'.) illustrate the division of the spenii.itogonia before they begin to develop into spermatocvtes. It is sujiposed that the sustentacular cells aid in the no\irishment r)f the spermatids during their transformation into spermatozoa, and that after the discharge of the hitter the cvtoplasmic proee>s is retnieted toward the base- ment-membrane, bringing with it the globules of fat and cytoplasmic fragments of the spermatids represented bv dark .spots and small round bodies in nearly all the figures. This retraetion 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 RErilODUCTIVE ORUANS. 229 Fig. 204. .:p32 A'li /.;!.•;'■,.■ i'^^m*^ ■/il7 Kio. 205. -^ 1 ■ r,- '-\' •J ^<2>.' • h 16 «-■ 4 ./' w Fig. 207. ii^iVTONi/fS— SI) 33 c i|^H'|f^^L_/( IS Fig. 209. sp3i f w8 w 230 NORMAL HISTOLOGY. Fig. 210. Fig. 21L li22 r^ wWQ^M^ t/^y ^.A «S:t ^h24 / to IV 9 w ) \ r-^ .^^^=^ Fig. 212. w w 10 / Fig. 213. .sp38 •^/il2 w/ «' iy f THE REPRODUCTIVE ORGANS. 231 Fig. 214. "basal plate," dii-cctiy upon tlic hascmciit-nicmbrane, where the edges of the basal plates an; in contaet, Ibrniing a sort of bed with depressions in its n|)per surface, in whieh the spermatogonia find lodgement. Tlu; cells of Sertoli possess a thiek cyto})lasmic process, whieh extends toward the lumen of the tubule, and to which thcst^ 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 ajjpearances of the various cells enumerated depend uj)on the stage in their activity whieh 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 s]>ermat()cytes. These now divide, each forming two secondary spermatocytes, which in turn divide, without an inter- Human spermatozoa. (Bohm and Davidott", after Retzius and Jensen.) The left fignre repre- sents the side view and the middle figure surface-view of a spermatozoon, a, head (nu- cleus) ; h, end-knob (centro- some ?) : c, middle piece ; d, tail of flagella; e, end-piece. The thickness of d may be owing to the presence of a above, takes place (Figs. 202-213). Each sheath surrounding the actual . , . , IT- • flagella, which projects from spermatid receives, in addition to its por- the sheath at e. tion of chromatin, a single centrosome. The spermatozoon, then, is derived from a corpuscle, the spermatid, which contains all the essential organs of a cell, differing from the gen- eral cells of the body, the somatic cells, only in possessing half the mediate distinct 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 reduc- tion ill chromatin, which was mentioned 232 NORMAL HISTOLOGY. usual number of chromosomes in its nucleus. It is unnecessary to pursue the chain of events througli 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 cilium 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. W^' ,*S ./"- :.!»?. •' .,^J^^'-' '^Oj Basement-membrane from seminiferous tube of the rat. (Ebncr.) m, endothelial cells com- posing the external layer ; I, cells, presumably leucocytes, intercalated between 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, njion which the epitlielial 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 uj)on 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 liuman testis. (Bohm and Pavidoff.) a, cubical or sccretorj- epithelium ; b, 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 va.sa 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 mu.scular 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, Avhich 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 off collaterals and finally terminate in teleneurites (Fig. 217). At the })resent time these neurons are believed to be without actual connection with each other, but to convey nervous stimuli by contact. The course of tlic 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-clement in the chain of nervous transmis- sion. Those neurites which carry stimuli from the nerve-centres 234 THE CEM'RAL NERVOUS SYSTEM. 235 to the periphery, aintrif'iij^al irnj)iil^t part indistinguishable through structural dif- ferences, but each containing fibres that play similar functional roles. 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 neuritc, with its collaterals ; e, collaterals from the lateral column ; /, collaterals to the anterior commissure ; g, central canal ; h, 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 k ; I, cell of the anterior horn, giving off a neurite dividing into an ascending and a descending branch (compare Fig. 224, JD) ; 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 s, 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 ncurites which divide into two or thi'ce branches while in the gray matter, the branches going to different columns of white matter. There are also cells with very short ncurites, which terminate in telenetirites 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 lUTvo-contro of" coiiiplex ci^iistitution, in wliieli neurons terminate in tcleneurites or arise in teledendrites. Some of the nenrons within the cord are eonfined to its substance, and constitute nervous connections between the diti'erent ])arts at various levels. These may be termed longitudinal commissural neurons, oc 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 neurites in the posterior spinal nerve-roots, with their collaterals ending in tcle- neurites within the gray matter (d). 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 neurites connected with cells at another level are shown, re-entering the gray matter, where they terminate in tcleneurites. 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 tcleneurites 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 antero-lateral portion of its substance (Fig. 218, 6; Fig. 221, /), 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 ])os- 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 gray commissure of the cord (Fig. 222, I). The col- laterals from the posterior column are divisible into four grouj)s : first, those which are given off in the lateral portion of that column (Fig. 222, G), 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 HISTOLOGY. which arise chiefly in the cohimn of Goll, pass through the sub- stance of KoUukU), 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, showingthe distribution within the gray matter of the collaterals from the neurites of the white matter. (R. y Cajal.) 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 e. 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 Avhite matter of the spinal cord they divide THE CENTRAL NERVOUS SYSTEM. 241 into two hranclics (Fi^. 221, /•). One of these ascends in tJie white snbstance and tiie other descends. Botli branches give off numer- ous collaterals, which penetrate the ^ray matter, ending in teh-nou- rites associated with the teledendrites of the cells in both the ante- rior and the posterior horns, and the column of Clarke. The main branches oLthe sensory neurite also enter the gray matter, after Fig. 223. Fig. 224. Fig. 223.— Diagram of the senso-raotory reflex collaterals in the cord. (R. y Cajal.) a, gan- glion-cell of the posterior nerve-root ; 6, division of its neurite into ascending and de- scending branches ; c, collaterals to anterior horn; rf, terminal teleneurites in the pos- terior horn ; e, motor cell of the anterior horn, with its processes. Fig. 224.— Longitudinal section of a part of the spinal cord, including a posterior nerve-root. Semidiagrammatic. (R. y Cajal.) A, posterior nerve-root; S, white substance of the cord ; O, gray matter; B, collateral teleneurites in the gray matter; C, cell with a single ascending neurite : D, cell with bifurcating neurite, terminating at Fand /; E, cell with a single descending neurite; F, G, terminal teleneurites ; a', collateral from a branch of the posterior root-neurite ; b', collateral from the main neurite before its bifurcation. following the posterior column for a short distance, and end in tele- neurites among the cells of the posterior horn and the substance of Rolando. The collaterals which pass to the anterior horns (Fig. 222, H, and Fig. 223, c) have to do with the origin of reflex cen- 16 242 NORMAL HISTOLOGY. trifngal 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. (K. y Cajal.) A, psycho-motor region in cerebral cortex ; B, spinal cord ; C, voluntary muscle ; D, spinal ganglion ; D', 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 iith. The sensory stimulus arising in the skin, iJ', is transmitted by the neuron dJ)ce to /, where it is communicated to the neuron fi/. The point / may be in the cord or in the medulla oblongata. In order to understand the origin of the anterior sj^inal nerve- roots we must first consider the course of the centrifugal neurites in the pyramidal tracts (Figs. 218, 219, 220). Those enter the gray matter and end in teleneurites, which are associated with the tele- THE CENTRAL NERVOUS SYSTEM. 243 dendrites of tlie cells in the anterior liorn, especial ly those which give off neiirites to the anterior roots of the spinal nerves (Fig. 221,./). The foregoing details may be summarized by means of tlic accom- panying diagram (Fig. ^-5), in which the course of a nervous stim- ulus is traoed from the org:in of sense in, e. r/., the skin, to the cortex of the cerebrum, where it is translated into a nervous im- j)ulse, the course of which is traced to the motor plates of the vol- untary muscles. The reflex mechanism wdiicli might at the same time be set into operation is not rej)resented in the diagram, but Avill be sufficiently obvious from an inspection of Fig. 223. It will be noticed in Fig. 225 that both the sensory stimulus and the motor impidse 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 ncurites 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-raotory reflexes illus- trated in Fig. 223. II. THE CEREBELLUM. The cerebellum is subdivided into a number of lamina^ by deep primary and shallow secondary fissures. The gray matter of the organ occupies the surfaces of these laminte, 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 jiear-shapcd bodies lying at the deep margin of the molecular layer. Their dendrites form an intricate arborescent system of branches extending perij)herally 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 Avhich they are situated, and the teledendrites come into relations with certain longitudinal neurites springing from the cells of the granular layer, 244 NORMAL HISTOLOGY. to be presently described. The neurites of the cells of Purkinje 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.) v'l, molecular layer of the gray matter; B, granular layer; C, white substance; a, cell of Purkinje; o, its neurite, giving off two recurrent collaterals ; h, b, stellate cells of the molecular layer; d, 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; fir, 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-cclls. 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. Tliese 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 CENTRAL NERVOUS SYSTEM. 245 sess neurltcs, whidi lie in the same plane with the arborescent dendrites of the cells of" PiirUinje, and send collaterals to end in a basket-work <»1" teleneiirites a|)|)lied to the bodies of the cells of Piirkinje. 'J'he terminal telenenrites of these stellate cells also end in the same situation. Other smaller collaterals extend toward the surface of Ihe 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 iieurites; f, slightly buUxms 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. 226, 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 ])lanes of which they run per[)en(licularly. 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 are 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, A, B, and C) ; while the cell-bodies of the third variety are large and polygonal (Fig. 229, D). 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- Till-: CEi\TRAL NERVOUS SYSTEM. 247 Fig. 228. lyin^ layers, which form iirboresccnt cxjKui.sions in the molccMihir hiycr, siiuihir to those of" the cells of" l'iirkiiij(! in the cerebellum, extending to the surface of the gray matter. Tiie large stellate cells of the molecular layer (Fig. 229, D) send their dendrites in various directions into the moleciriur 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 neuritcs 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 (^1, J5, C, Fig. 229) are considered to be the autochthonous cells of the cerebral cortex — /. c, 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 Vertical section of the cerebral cor- tex, showing its layers. (R. y cerebml 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 Cajal.) 1, molecular layer; S, layer of the small pyramidal cells ; 3, layer of the large pyram- idal cells ; 4, layer of polymor^ phic cells ; 5, white matter. 248 NORMAL HISTOLOGY. Fig. 229. Cells of the molecular layer of the cerebral cortex. (R. y Cajal.) A, C, small spindle-shaped cells ; B, small stellate cell ; D, large stellate cell. The branches marked c are neurites. 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, D, poly- morphic cells in the fourth layer ; E, centripetal neurite from distant nerve-centres ; J^, 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. (R. 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 ; 5, 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 tlicir entrance into the Avhite matter, these neurites give oil' eolUiterals, which branch and end in terminal bulbous expansions without breaking up into a set of teleneurites. The irreguhir 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, e) or into the second layer of the gray matter (Fig. 231, 6) ; 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 grav matter of the cortex also receives centripetal neurites from the white matter, which give oflf 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- ridr 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 Avhich further collaterals may be given off, after which the main neurite probably passes into the pyramidal tracts of the cord through the cerebral crus (Fig. 232, a). The commissure-fibres (Fig. 232, 6, 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.) A, 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 6 is a second similar cell, the neurite from which contributes no branch to the corpus callosum. b, 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. (R. 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 diflerent 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 CEyXRAL XERVOUS SYSTEM. 251 form the great bulk of the wliite .substance, where tliey 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 oft* numerous collaterals and teleneurites, w^hich 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 probal)le 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 incalculal)le. 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 l>een 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 apparently 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 apj)carauce, as, for example, in the second layer of the cerebellar cortex. The brain and s]>inal cord are invested by a meml^rane 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 nervous 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 are centrifugal teleneurites subserving the functions Fig. 234. Fig. 235. Tactile corpuscles. Fig. 234.— Meissner's corpuscle, from the human cerium. (Bijhm 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 ; c, 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 ORGANS OF THE SPECIAL SENSES. 253 Those are situated in the coriuni, ti»e iuriiier lying in some of the pupil he pr()je(;ting 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 K ran so. The tactilt! corpuscles of Meissner (Fig. 234) consist of a group of epithelial cells closely associated with the teledcndrites of a nerve-libre. The cells arc closely compacted together to form an ellipsoid body. 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 cndoneurium 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- dcndrites, that form a complex tangle within the cavity of the cor- puscle. There appear to be no cells among the teledcndrites, 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 lamelhTC, 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 teledcndrites within the central cavity. The " genital corpuscles " which arc 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 lamellae. The nervous impulses inaugurated in the tactile and Pacinian 254 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 papillse 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 witli nervous functions. They may, pos- sibly, be regarded as peculiar neurons; their distal proces.ses, which receive stimuli at the pore, being the dendrite, while the proximal process is the nenrite. 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 TlIK ORGANS OF TllIC ,Sl'hVIAL SI'JNSI'JS. 255 with the t('k!(UMuli-itc'.s ut" ncrvc'-iibrcs .supplied to the ta.ste-biid (Fig. 237). The stratified epithelium surrounding the taste-buds, as elsewhere, contains teledendrites from sensory nerves. 3. Smell. — The oH'actory organ occupies a small area at the top of the nasal vault, and extends for a short distance uj)on the sep- tum and extprual Mall. Its expo.sed surface is about e(pial to that Fig. 237. Diagram of a taste-bud and its ik rvmis supply. (Dogiel.) a, radicle of the gustatory nerve ; /), 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 j)ortion. The respiratorv ])ortion 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 submncous 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 eiiithelium 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. Ba in Vertical section through the olfactory mucous membrane of the human nose. (Bruan.) «, nuclei of the columnar epithelial cells; rz, nuclei of the nervous or olfactory cells lying among those of the epithelium ; 6s, 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 lymphadcnoid tissues beneath the epithelium; Ba, duet of a gland of Bowman; Bb, dilated subepithelial portion of the duct, receiving several of the tubular acini, Bt. The connection between the duct and tubes is not shown, n, n, branches of the olfactory nerve ; ri*, 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 througli the cribriform plate of the ethmoid bone to the olfactory bulb of the brain, where THE ORGANS OF THE SPECIAL SENSES. Fig. 239. 257 iFy^ 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.l, cuticle of the columnar epithelium, which is not continued over the end of the nervous cell. The cuticle of neighborinjj 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." 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 neurogliar 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 Avithin 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 arc transmitted to the glomeruli, where they leave the first neuron, being communicated to the second, represented by the THE Onr.ANS OF THE SPECIAL SESSES. 259 mitral cc^lls uikI their processes, by wliicli they arc conveyed to the cerebral cortex. In its passage through this tract numerous collat- Diagram of the nervous mechanism of the olfactory apparatus. (R. y Cajal.) a, olfactory portion of the nasal mncous membrane ; b, 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, in, cells of the fifth or granular layer ; c7, olfactory tract ; g, cerebral cor- tex ; /i, 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 distrilnition of the auditory nerve within the mucous membrane of the crista acustica. (Nicmack.) The bodies of the hair-cells are dotted. Between them are the cells of Dciters, 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 laver of epithelium containing two sorts of cells : first, ciliated cells, which are somewhat flask-shapod 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, which 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 SENSES. 261 varies with the functional activities of tlic or<>;an. When the eye has been exposed to light the pigment is found lying deeply between the rods. When the eye has Ixien at rest for some time the pigment is retracted in greater or less degree within the l)ody of the cell. 2. The rods and eones are the terminal structures of cells which extend from the fifth layer to the first. The nuclei of these cells Fig. 243. Tin, 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, s, pigmented epithelial cells; c, at the bottom of the external limiting membrane, rods ; b, cone cells ; c-h, ganglion-cells of the sixth layer connecting the fourth layer with the eighth; i, horizontal cell sending a process into the seventh layer; A-iy, "spongioblasts," or neurons of the third type (Fig. 217); r-u', ganglion-cells of the eighth layer; x, sustentacular cell of Miiller, with striated upper end forming a part of the external limiting membrane; y, y, neuroglia-cells. It should be 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 are distributed in the inner graniilar or sixth layer. The light entering the eye passes through the layers represented in the lower jjart 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 cuticularized outer ends of certain sustentacular epithelial cells, the "cells of 262 NORMAL HISTOLOGY. Miiller" (Fig. 243, a-), 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 crranular 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 Avhich 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 sixtli 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 neuritcs that come into relation in the seventh layer with the den- drites of ganglion-colls lying in the eighth layer; second, neurons of the third type, shown in Fig. 217, which, in this situation liave been called " spongioblasts." These, which we may regard as association-neurons, form two groups : first, those which send Tin-: oiiuAxs of tiu-: special senses. 263 processes into the fif'tli layer; and, second, those wliich send their processes into the seventh layer; but, aside from the neurons in- cluded in these two groups, tiiere are cca'tain cells (Fig. 21.'>, i) which send processes into both tiie fil'th and the seventh layers. 7. The seventh, inner molecular or " inner ])lexiforni" layer owes its delicatestructure 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. se 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 Avill be observed in Fig. 24.3 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. Diagramof the nervous mechanism of vision. (R. y Cajal.) ^.retina; /;, optic nerve; C, corpns jreniculatum. a, cone : h, rod ; c. d. bipolar nerve-cells of the outer granular layer ; e, ganKlion-eell ; /, centrifugal teleneurites ; 17, " spongioblast " ; /), 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- fiinnedj spme of whinh 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 due 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 desrenerations are changes in which one of the resultsjs-thfi conversion of a piu't of the normal structure into some other siihr 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. 265 266 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 ; I 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 DKdESKRATIONS AND IM'lLTllA TIONS. 2G7 are forniod at tlic expense of the cytoplasm, or, at any rate, the cytophisni (lisa])[)eai's as they aceiiniiilate. It" the change be only moderate in degree, it is possible for the cell to retnrn to its normal condition. 'J'he gramdes then disap- pear, the cell recovers its original size, and there is no trace of the morbid condition left. Bnt the degeneration may i)e too extensive to permit of recovery. The cell then sntt'ers disintegration; the grannies become more abnndant, the normal cytoplasm disappears, Fig. 245. « .$ & Parenchymatous nephritis, n, cross-section of a convoluted tubule of the kidney, the lin- injr epithelium of which is the seat of albuminoid defeneration. The cells are swollen ami their bodies filled with abnormally coarse granules. The cells to the left are so far disintegrated that tlie nuclei have lost most of tlieir 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 atfeeted, are represented in obli(iue section, b, tubule with low, unaflTected epithelium, the nuclei of which stain deeply: r, 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 htematoxylin and eosin. and the nuclens falls into fragments (" karyolysis "), the whole cell being rednced to a granular debris exhibiting no evidence of organ- ization (Fig. 245). 268 HISTOLOGY OF THE MORBID PROCESSES. 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. r )!■ "jj>- C '^""^^^^iL-iiiay Fatty degeneration of the cardiac muscle. (Israel.) In some portions of the preparation the cross-striations of the coniractile substance are retained. In these portions the fatty metamorpho.sis 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. Tiiey have been omitted from the figure. Specimen prepared by teasing the fresh tissue. unchanged upon treatment with weak acids or alkalies, and is stained a dark brown or black by solutions of osmic acid (see Fig. 186), reactions which distinguish fatty from albuminoid granules. They arc, 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 has 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, iusufficient 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 a])plied injury, or it may be occasioned by a sudden diminution, but not complete arrest, of the nutrient supj)ly; c //,, by the iiicoiuplcte plugging of a bloodvessel by an embolus. All)uniiiioid fNEILTRATfONS. 271 food taken into tlie system, it is evident that any eondition inter- fering witii digestion and absorption nuist inflnence the general nntrient supply. In fevers the ghinds of the alimentary tract, as Avell as the cells of other organs, arc affected with albuminoid dcgencnition. Their secretions ai'e diminished or altered, the diges- tion arrested in greater or less degree, and the a[)p('tite lost or per- verted. For these reasons the diet must he adjusted, not only to the needs of the ])atient, l)ut also to his powers of digestion. But this state is established only after the degenerative changes have been inaugurated, and does not explain the way in which they start. If we bear in mind that the febrile condition is the result of a toxic state of the blood and nutrient fluids, and that the poisons present are probably obnoxious to the cells, we shall find no dif- ficulty in understanding that the cells might reject a nutrient supply so vitiated. Where we can observe the action of cells, we know that they are repelled by certain substances, and it apjx'ars reason- able to suppose that cells which we cannot directly study during life possess similar powers of rejection. If this view b(! correct, the very condition which induces fever would also interfere with the proper nutrition of the cells. The causation of fever, according to this argument, is to be sought in the toxic condition of the blood and other nutrient fluids, the poisons disturbing the action of the thermo-regulating mechan- ism of the nervous system and also interfering with the nutrition of the cells of the body. As soon as fever begins, its influence upon the cells is to stimulate their activities, for we know that a moderate elevation of temperature causes an increased metabolism in those cells that we can study while alive. It is, conscquentlv, not necessary that a direct functional demand should bear upon the cells in order that the chemical changes within them be aug- mented. The rise of temperature is sufficient to account for increased metabolism, which, in turn, implies a liberation of heat, and, therefore, an aggravation of the morbid condition. The increase of noxious waste-products of cellular activity, which enter the circulating fluids, may also add to its toxicity. But, in addition to this thermal cause of increased metabolism, the toxoemia throws extra work upon those cells that are charged with the function of maintaining the quality of the blood or Ivmph. The kidney contains such cells, and is one of the organs most likely to be severely affected with albuminoid degeneration (acute paren- 272 HISTOLOGY OF THE MORBID PROCESSES. chymatous nephritis, Fig. 245). The spleen and lymphatic glands are also exposed to an increased functional demand, and respond in an increase of their active tissues, which may pass into degener- ative conditions if the task be greater than they are able to cope with successfully. In the other conditions in which albuminoid degeneration is found the factors determining its causation appear less complicated than in the fevers. Many of the acute inflammatory processes are accompanied by a rise of temperature, due to the absorption of poisons from the seat of the inflammation, and then the degenera- tion will be more Avidely distributed than in those cases in which the general reaction is less marked or entirely absent. But the tissues immediately involved in the inflammatory process will suffer in their nutrition, whether toxaemia be present or not, and in certain of them the result will be a degeneration, while in others it will be necrosis or death. In the case of albuminoid degeneration follow- ing incomplete embolism the explanation is even simpler ; for here the nutrition is directly reduced by the mechanical effect of a partial plugging of a bloodvessel. In all the cases in which albuminoid degeneration occurs in a comparatively pure form the cause is an acute one — i. e., the cells are called upon to meet a sudden change of condition in their activities and nutrition : the former being, as a rule, increased ; the latter, probably always diminished. The explanation which can be offered of the way in which fatty degeneration is brought about is very similar to that already given for albuminoid degeneration. In fatty degeneration the emergency which the cells have to meet is less sudden than in albuminoid degeneration. The adverse con- ditions to which they are subjected are more slowly developed, though not necessarily less serious. The cells appear to be able to accommodate themselves to a considerable extent to the abnormal circumstances, but eventually their powers of metabolism are dis- turbed and they are incapable of utilizing the less readily available food-materials. When the organized proteids are then drawn upon their nitrogen appears to be completely used, so that no residual albuminoid substances are deposited in granular form^ l2utj3i_rem-^ nant of the cytoplasm, free from nitrogen and taking the form of fat, the least readily oxidized form of food, is left, If, now, the cells continue to a])propriate and utilize albuminoid food-material, nJ'XihWL'RATIONS AND INFILTRATIONS. 273 this fatty residue would accumulate within the cyl()i)lasni. Fatty foods would, of course, he little, if at all, utilized. This leads to the inference that one of the chief features in the disturhed nietai)oIisni of the cell is an inahility tojmng about the, "*+• -con)plete_oxulations that normally take [)hic(^J.ii the, cytoplasm^ and when we examine the conditions in which fatty degeneration occurs we notice that a (>;roup of then; are such as would involve a dimin- ished Miuoimt of oxv;c'iK'r:itioii, also occurs iu iullaimiiations wlicn tlie serous constituoiit of the exudate is proiiiiiieiit. fi. Mucous Degeneration. — 'I'his ioriu of (IcLceueration lias its intr- nuil analot;ue in the elaboration of mucus hy the epithelial cells covering miMiy of the mucous membranes or lining mucous glands. ¥iG. 250. ^\)»*5 Vacnolation of striatofl muscle. (N'olkiiiann.) The specimen is from the rectus abdominis muscle from a case of typhoid fever. The cross-sections of the muscle-fibres contain spaces within the contractile substance, which are tilled with a clear, fluid serum. The fibres so infiltrated are larger than those containing no such vacuoles. The cavities are, therefore, not produced at the expense of the contractile substance. Between the fibres is the in- termuscular, vascularized fibrous tissue, forming the interstitial tissue of the muscu- lar organ. But the elaboration of mucin is not confined to epithelium. It may be produced by the cells of the connective tissues, appearing among the intercellular substances. This is most marked in mucous tissue, where the general character of the tissue is determined by the mucus in the intercellular substance. Tliere is also a comparatively small amount of mucus in other forms of connective tissue, espe- cially in the fibrous varieties. Under morbid conditions, which we are not able exactly to define, this production of mucus is increased. In epithelial and other cells 278 HISTOLOGY OF THE MORBID PROCESSES. its production may involve a destruction of the cytoplasm, which appears to be sacrificed. A similar transformation or replacement of the normal intercellular substances may also occur in the connec- tive tissues, such as bone, cartilage, fat, or fibrous tissue, which then contain more than the normal proportion of mucin. This propor- tion may be so great as to alter the physical properties of the tissue. In these cases the cells may undergo mucous degeneration, or they may ultimately suffer a fatty degeneration. It is a question to what extent the cells are active in the substitution of mucous for the usual intercellular substances, the manner in which it is produced being as yet undetermined. The mucus is a clear, viscid fluid, which appears to be a mixture of various substances containing either mucin or pseudomucin. These substances are precipitated by alcohol, so that in hardened specimens the mucus becomes granular or is streaked with linear coagula. Hffiraatoxylin usually stains the whole mass a faint blue ; the granules and streaks a little more intensely than the clearer por- tions. This staining serves to distinguish the mucus from a serous fluid, which is also made granular by the coagulating influence of alcohol upon the albumin it contains. Mucous degeneration of the epithelia is a frequent accompani- ment of inflammation of the mucous membranes, where it appears to be due to an excessive stimulation of the functional activities of the cells. A similar mucous degeneration of epithelial cells is also very common in tumors ; e. g., the cystomata of the ovary and colloid cancer. 7. Colloid Degeneration. — This is a form of degeneration in which the substance of cells is converted into a clear, homogeneous, gelat- inous material of greater consistency than mucus, and, unlike the latter, is not precipitated by alcohol, so that in hardened specimens it retains its homogeneous appearance. The production of colloid seems to be normal in the thyroid gland after the attainment of a certain age. In this situation the colloid material is formed in the cells of the alveoli and then dis- charged into their lumina, where it forms a mass that may com- pletely fill its cavity (P'ig. 154); but the cells of the thyroid not infrequently suffer destruction in the elaboration of the colloid material, so that even here the process partakes of a degenerative character. The material forming the hyaline casts in various kinds of DEUESIlRA TloyS . l MJ ISFIL til 1 TIONS. 279 nephritis appears to be colloid elaborated by the cells lining the renal tubules, but those casts may not always owe their origin to this form of degeneration. Fi(i. -J.-)!. # lft?fe Fio. 252. \ f.^> Hyaline degeneration. (Ernst.) Fig. 201.— Hyaline degreneration of cells in the choroid plexus. In this case the hyaline material appears to be derived from the cytoplasm of the cidl.s, the process constituting a true degeneration. Transitional conditions from the unchanged cells to masses of hyaline without traces of cellular structure are fjund in the specimen. Fig. 252. — Hyaline degeneration of the capillary walls in a psammoma of the dura mater. Here the endothelial lining of the capillaries is intact, the hyaline material being out- side of it. This disposition of the hyaline would lead to the inference that in this case it was the result of infiltration. It is prol)able that the composition of colloid is not alwavs the same. It is identified by the facts that it is a clear, structureless substance, derived from cells and not presenting the characteristics of mucus. The cau.>^es and mode of its production are unknown. 280 HISTOLOGY OF THE MORBID PROCESSES. 8. Hyaline Degeneration. — This term is used to designate the occurrence of a material similar to colloid, which appears chiefly in the intercelhilar substances or in the interstices of the tissues, and is apparently not immediately derived from the substance of cells. It is a question whether it should, in such cases, be regarded as a degeneration — i. e., the result of a transformation of pre-exi stent normal structures — or whether it is not a form of infiltration, the material being simply deposited between the normal structures, which may atrophy and disappear in consequence of its presence. Its most common site is beneath the endothelial linings of the bloodvessels, where it forms a homogeneous layer, greatly thicken- ing the vascular wall and often causing a narrowing of the lumen of the vessel (Figs. 251 and 252). It may also affect the fibrous tissues, replacing the intercellular substances with hyaline material, made up of an agglomeration of little masses, or appearing quite homogeneous. The cells of the tissues gradually undergo atrophy and disappear, but do not seem in most cases to suffer a transforma- tion into hyaline substance. In some instances, however, the cyto- plasm of the cells appears to undergo a hyaline transformation (Fig. 251). A hyaline transformation sometimes affects thrombi, which lose their fibrinous character and become homogeneous. Hyaline material may take a faint bluish tint when treated with hsematoxylin, or it may remain colorless. Various attempts have been made to define more clearly the con- ceptions of colloid and hyaline substances, and to distinguish them by means of reactions with different staining-fluids. These attempts have not led to satisfactory results, probably because the colloid and hyaline substances are mixtures of various chemical compounds ; the whole subjoct awaits further investigation. 9. Keratoid Degeneration. — This form of degeneration is a trans- formation of the cytoplasm into a substance called keratin, which gives to horn, the nails, etc., their peculiar character. It is nor- mally produced in the epidermis, where this degenerative process is not pathological. The transformation a])])ears to involve the pre- liminary formation of a substance called eleidin (Fig. 175), the chemical nature of which is unknown, which sul)sequently changes into keratin. These two substances may be distinguished by the facts that eleidin is deeply stained by carmiiK! and not by fnchsin, while keratin is readily stained by the latter dye. DEGENERATIONS AND INFILTRATIONS. 281 The cells in the epithelial pearls of e})itheli<)niatu often nndergo these degenerative changes, producing large masses of eleidin or keratin. The change in these cases may be considered as due to a retention of this normal tendency by the epidermal epithelium under the abnormal conditions in which it is placed in the tumor. In those caees of metaplasia in which columnar epithelium becomes convertef atri.i)h\ i< probably attributable in some measure to a (limiiiished flow of bl(M.«l to the part, for in health, when the functional aitivity (»f an organ is c-alled into play, there i.s an in- creased voIhuic of bluod conveyed to that organ. But this element in the innutrition docs not accoiuit for the whole process. The intracellular metabolism also falls below the normal level, and this appears to reduce the state of nutrition of the cellular constituents. 2. Pressure-atrophy ( Figs. 257 and 25s ). — "When a part is sub- jected to iiKKleratc but constant, or oft-repeated pressure, it under- o-oes atrophy through a disturbance in its nutrition. This may be Fig. 257. Section from an emphysematous lung:. (Ribbort. > The pulmonary alveoli are enlarged ; their walls are stretched and thinned : atrophied because of repeated excessive air-pressure within the alveoli. In more extreme cases of emphysema the atrophy of the alveolar walls may lead to their total destruction in places, so that the cavities of neighboring alveoli communicate. (Compare with Fig. 150.) partly due to a direct influence exerted by the pressure upon the processes carried on in the cells of the tissue, but it is probable that interference with the circulation, including the lymph-currents, has a greater influence in bringing about the lack of nourishment. Ex- amples of this form of atro[)hv are furnished by cases in which a contracting cicatricial tissue is formed between the ]virenchymatous cells of an organ, as the result of a chronic interstitial inflammation. Those cells then undergo atrophy and may eventually disappear (Fig. 286 HISTOLOGY OF THE MORBID PROCESSES. 288). In passive hypersemia of the liver the cells situated around the central veins of the lobules suffer atrophy. This is due in part to the pressure exerted u])on them, in part to an interruption of the lymphatic circulation, and in part to the fact that the blood reaches them last in its course through the organ and is probably less richly provided with oxygen and other nutritive materials than when it Fig. 258. 5,, X ■ .•'V ^?-:-rf^^'^^<^. "< . ' Lobule of the liver, showing atrophy from chronic passive congestion. (Eibhert.) 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, where 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 ti.ssue 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, "^rhus pressure upon the Avails of a bloodvessel may cause them to increa.se in thickness. Aside from the two forms already mentioned, atrophy may be the result of a diminution in the nutritive su])ply : local, as the result of disease in the vessels of a part ; general, Avhen all the vessels are ATiioriiY. 287 afibctcd witli iliseasc, or when the general nntrition of the hodv is rethiccd. ]ioth these causes operate in the general condition known as " senile atrophy." More obscure forms of atrophy are those which aj)pear to be occasioned by lesions of troi)hic nerves, or are caused by toxic con- ditions; e.ff., lead-poisoiiJr/g. 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 ])erform. This increase may take the form of hypertrophy or that of hyperplasia. The muscular tissues meet the demand by 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 tlic supply of nutrition. The nature of the tissue also iuflaenccs the result. In general, it may be stated that tissues of high specialization are less capable of either hypertrophy or hyperplasia than those less specialized, and that hypertrophy is the rule in tissues of higher function, while 28S UYrKiiTRoriiY Ayjj uyrEnrLAsiA. 289 liypcrphisia is more eomnion in those of lower function, where the fornuitive powers of tiie cells are less in abeyance. Compensatory iivpertkopiiy is a terra applied to functional hypertrophy or liyper|)lasia followiiiji; the destriuition of an ortrun or part of an organ. This leads to an in(U"ease 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. ^ Necrosis of part of an hepatic lobule, (v. Meister.) o, necrosed cells, the nuclei of which have lost their affinity for dyes: 6, 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 atfected 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 hypertrojihy of the heart by throwing more labor upon that organ in order that the remaining renal parenchyma may perform the work demanded t)f the kidneys. In like manner the auxiliary muscles of respiration may become hypertrophic in cases of embarrassed respiration.^ Functional hypertrophy may also find expression among the con- ' 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 pliysical 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 eifect 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, witiiout passing throngh an intermediate stiige of iiuliticrent 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. Mctaphisia only results in the formation of a tissue closely allied to tiiat 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 info 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 whicli, 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 stri[)ped off and mounted in a drop of serum, the cells composing it may be readily seen under the microscope. AVhile 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 tliat 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 deatli 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. * ■';•\'.r:•>- Changes in the nuclei of renal epithelial cells incident to necrosis. (Schmaus.) 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 di.sappearance of the chromatin without a coincident disinte- gration of the form of the nucleus-chromolysis. 1. Coagulation-necrosis. — Wlicn the tissues that have suffered death liberate fibrinoplastic substances and fil)rin-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 CHANG KS DUE TO DAMACK 295 gone coagulatiun-necrosis (Fig. 2G3). Wlieii 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 choosy dogonoration (p. 274). 2. Colliquative Necrosis (Fig. 2S1). — This form ol" necrosis is fol- lowed by an imbibition of fluid, occasioning a disintegration of the Fig. 2G3. e. j e Edge of a diphtheritic membrane. Section from the human uvula. (Zieglcr.) a, normal stratified epithelium ; 6, 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, cedematous subepithelial fibrous tissue containing fibrin and leucocytes ; c, bloodvessels ; /, haemorrhage ; 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. Tliis 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. ExcAPSULATiox. — 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. Gaxgeexe. — This occurs in two forms, distinguished as drv 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 granulation-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 idcer. In those cases of necrosis in which the necrosed tissues are not speedily absorbed the dead mass is known as a " sequestrum," and STRUCTURAL CIIASGES DUE TO DAMAGE. 297 the zone of iiiHanimation stpanitino; 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 (lirticult to frame an aeetirate detinirion of inflammation, for the reason that the term includes a number of different conceptions that cannot he readily expressed in concise form. In general, it mav l)e stated that inflammation is a prwess of repair following a limited damage to the tissues. The injurious agent acting ujKjn a part must inflict a certain amount of damage in order to bring about inflammation : if its action be slight, it will cau.se only an evanescent irritation which does not pa.ss 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 lias then been removed. In considering this example we must distinguish between those destructive effects that are due to the damagins: 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,. iu 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 the Circulation. — The vessels most seri- ouslv 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 eifect 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, e. 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, probably as the result of the damage they have sustained in common with the other tissues, allowing a greater amount of fluid to ])ass 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 CHAXCES DUE TO DAMAGE. 299 Thus, two iuHiionces a])pc:ir to check the How of tlic blood after the intliiininatory process has been iiuuigiirated : (1) a (liminution 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 tlie resistance is added as soon as fhe current has becomes slowed beyond a certain point. During the uonnally rapid tl(»w 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- ])eudod jiarticles in fluids circulating in a tube; but if the rate of flow be diminished beyond a certain point, the suspended particles Fig. 264. —b Fig. 265. Fig. 266. Positions of the corpuscles in circulating blood. (Ebcrth and Schimmelbusch.) Fip:. 264. — Appearance when the velocity of the circulation is normal: a, axial column of corpuscles, both red and white, in such rapid movement that individual corpuscles can- not be distinguished. Occasionally a white corpuscle is thrown from the axial mass and appears in the plasmic zone. b. Fig. 2f.ri.—.\ppea ranee when the velocity of the circulation is moderately reduced. The zone b contains numerous leucocytes. Fig. 2t)6.— Appearance when the current of blood is sluggish: a, red corpuscles, still in the axis ; b, peripheral zone, containing leucocytes, d, and l)lood-plates, c. When stasis is fully established the red corpuscles also invade the peripheral zone. The figures are from observniious made on the vessels of a dog's omentum during life. invade the fluid zone at the periphery of the current, tho.>se Avhich are specifically most nearly of the same weight as the fluid passing most freely into it. In the case of the blood tho.se particles are the leucocytes, which are lighter than the red corpuscles, and, as the 300 HISTOLOGY OF THE MORBID PROCESSES. current slackens, it is these which first make their way into the clear serum at the perijihery of the stream and soon come in contact with the vascular wall (Figs. 265 and 266). Here, by virtue of their adhesiveness, they cling to the endothelium, and must materially increase the difficulty with which the blood is forced forward and promote stasis. While the blood is circulating freely in the vessels the leucocytes it contains are subjected to repeated mechanical shocks through contact with other corpuscles or with the walls of the vessels where these branch or form sharp curves. These blows cause the cytoplasm to contract, maintaining the globular form of the cor- puscle ; but when they come to rest upon the surface of the vascular wall, as may occasionally happen under normal circumstances, and is always the case in acute inflammations, the leucocytes have an op- portunity to execute the movements which have been called "amoe- boid," from their resemblance to those displayed by the amoeba. The leucocytes send out pseudopodial processes and creep along the surface of the vessel-wall. We must bear in mind that at this time the capillary vessels are dilated, and that the cement between the endothelial cells is somewhat stretched and thinned. The passage of the pseudopodia of the leucocytes through the cement is facilitated by these circumstances, so that soon after the circulation has become sloAved there is a passage of leucocytes through the walls of the ves- sels into the spaces in the surrounding tissues. This escape of the leucocytes is called their " emigration " (Fig. 267). The number Fig. 267. Emigration of leucocytes through a capillary wall. (Engelmann.) a. leucocyte just leaving one of the pseudostomata between the endothelial cells of the capillary wall ; 6, leucocyte partly within and partly outside of the capillary; c, nucleus of an endothelial cell of the capillary wall. of leucocytes that escape from the Ijlood in tlie manner described is variable. In some varieties of inflammation the tissues outside of the vessels contain substances that have an attraction for the leuco- STRUCTURAL CHANGES DUE TO DAMAGE. .HOI eytes. This is particularly tin- case when the cause of the inflam- mation is an infection with bacteria. Under those circumstances the leucocytes that eniith('lia, open minute channels through which the red corpuscles of the bUH>d may be pressed into the surrounding tissues, when they come in contact with the vascular wall after stasis (complete arrest of the circulation) has become established. These corpuscles are soft, and can be forced through orifices much smaller than their normal diameters; but the number that escape from the vessels varies greatly in different cases of inflammation, and it is probable that the inteji-ritv of the vascular wall is more affected when the niunber is great than wlien it is slight, and that the leucocytes prepare the way for only a portion of the red corpuscles that escape from the vessel in tiiose cases in which large numbers pass into the surrounding tissues. The escape of red corpuscles from a vessel ■without obvious rupture of its walls is called " diapedesis." As a result of the processes already described, it will be observed that three of its constituents pass from the blood into the sur- rounding tissues : (1) serum, (2) leucocytes, and (3) red blood-cor- puscles. These constitute what is known as the " exudate." But to these three a fourth constituent is soon added, namely, fibrin. The formation of fibrin is still awaiting a perfectly clear explana- tion, but it is usually assumed to be the result of the interaction of three substances : (1) fibrinogen, derived from the })lasma of the blood ; (2) fibrinoplastin and (.3) fibrin-ferment, both of which may come from the bodies of cells. In the exudate of acute inflamma- tion all of these elements necessary for the formation of fibrin are present in greater or less amount. (See explanation of fibrin- formation on p. 127.) As found in the tis.sues, therefore, the exu- date consists of serum, fibrin, leucocytes, and red corpuscles (Fig. 268). But in different cases their relative abundance differs, and the acute inflammations have been rou^hlv classified accordins: to the character of the exudate. Thus, the serous inflammations are those in which serum predominates in the exudate. In like manner iuHammations are designated by the terms fibrinous, hsemorrhagic, and jiurulent (when the leucocytes predominate), or sero-fibrinous, sero-purulent, fibrino-purulent, etc. These terms are descriptive, and merely indicate variations in the proportions 302 HISTOLOGY OF THE MORBID PROCESSES. of* the different constituents in the exudate. The general nature of the process is the same in all cases. We are now in a position to explain four of the cardinal symp- toms of acute inflammation. The increase of temperature and the redness (calor and rubor) are attributable to the hyperaemia of the part and its surroundings. The SAvelling and pain (tumor and dolor) are caused, at least chiefly, by the presence of the exudate. The suspension of function, or fifth cardinal symptom of acute Fig. 268. >■>■ 4 * 0 :^ ((^^'uii'MshA^^Ii^M^^M d e. f Section from lung in the second or exudative stage of croupous pneumonia : o, endothelial wall of a small vein ; b, blood within the vein, unusually rich in leucocytes, which have collected during the slowing of the circulation. The line b yjoints to the nucleus of a leucocyte. Part of the blood has fallen out of the section during its preparation, c, leu- cocytes beneath the endothelium of the vascular wall ; d, oedematous fibrous tissue sur- rounding the vessel. The fibres of the tissue have been separated by the e.xuded 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, e, 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 ])orhaps to an interruption of the normal nervous mechanism. All these disturbing factors are present, and may vary in their potency in different cai^es. 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 CIIAydES DUE TO DAMAGK 303 rcgartk'cl as constitutiii*:; the lUdruvtire phasic ot" acute iiiHainiiia- tion. 2. The Fixed Elements of the Tissues. — It is evident that tlie cause ot" tlaniMt;v itsi-lt", or the (hstiu-hancos of nutrition resultinj^ froui the ehan<;es in the eireulation, must either cause rapid (h/ath, necrosis, or that slower t'orni of (U'ath entailed by a relativelv in- sufficient supply of nourishment, which has been described in the chapter on the deiicnerations. The cells are either killed at once, or are starved within a t-ertain radius of the point at which the cause of the iufiannnation 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 miglit cause degeneration in some and not in others, so 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 jiowers of recuperation undergo a species of rejuvenescence, returning to a comparatively undifler- entiated condition, in w'hich their powers of reproduction and tissue- formation are revived. It is as though thev 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 — e. [/., 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 colls 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 Avhy 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 they play a loss 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 undegeneratod cells of higher function, and from this it follows that the defects in the tissues are made good by a proliferation of connective tissue, accomjianied 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 colls of the connective tissues enlarge and become more cytoplasmic, and tlioir nuclei become richer in chrouKitin. They then divide by the indirect process, giving rise to a number of splieroidal cells, which, together Avith newly devel- oj)ed loops of caj)illary 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 phagocytes (Fig. 269). The young vascular loops that supply the granulation-tissue are STRUCTURAL CHANUES DUE TO DAMAGE. 305 Fig. 2G9. Section from adipose tissue in the neighborhood of a phlej^monous inflammation due to infection witli streptococci. ((Jrawitz.) F, the bouu(hiries of fat-cells, the tissue repre- sented being the connective tissue between those cells. Four large karyokinetic tigures are 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^ are 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 oedema. procluood tliroii2:h a .'similar rejuvenescence of tlie endothelial cells of the older capillaries. Tho.se 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. (Xikiforoff.) In both A and B two capil- laries arc represented, a, young connective-tissue cell : n\, karyokinetic figures in such cells ; b, ftj, bo, 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 with other capillaries. Sub- sequently these solid columns or bands of cells become channelled, the cells forming the w^alls 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-Hirsehfeld.) 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 oif, 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 diiferentiation, 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 ])rocess the cells dwindle in size as the intercellular sub.stances 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 CJJASaUS DUK TO DAMAGE. 307 in the nutrition of the tissiu,'. There is a nianife.st adviuiljijjjc; to the wiiole organism in this absence of" lymphatics in grannhition- tissiie, for the absorption of injurious substances from the region bevond the granuhitions is hindered. Jiut the nutrition of the granuhitions 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) ; b, 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 deficiency in its organization may not be apparent ; but as the intercellular suKstances 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 pericarditis : a, fibrous tissue, almost devoid of nuclei and vessels derived from granulation-tissue; 6, 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 modificnl 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 enesccnce affects the tissues of the j)eriosteiini and eudostcum, as well as the surroiiiiding eonneetive tissue of the fibrous type. In the subsequent differentiation of the granuhition-tissue, which in this case is called the " callus," those cells which ha\'e been derived from tiie periosteum and endosteuni 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 " (r. 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. Xor 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 ])urposc 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 clianges ; the tissue will be diifusely stained, the nuclei either unstained, only faintly tinged, or broken into fragments that take the dye in vari- ous intensities (Fig. 274). Around this necrosed tissue there Fig. 274. O /,%-^- ^ 'li'»\- >*>• Secondary infection of the kidney in a case ol cryfsiiiulas. (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 case 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. Tiie 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 jjortion 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 ill AM IKS DUE TO UAMAGK Yu.. 27.',. 311 *? % •** S^ <* "Tr. ^^•' . 1 O'fr^.i '% ■*!^ Beginning abscess -formation in the kidney. (Fiiulliaber.) The suppurative inflam- mation is due to secondary infection by bacilli carried to the kidiR-y from a phleg- monous inflammation of tlie neck, a, a, bacilli in the capsule of a Malpighian body, the necrotic glomerulus of which is seen in the upper half of the tigure; 6, 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 ba.sement-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 \N fJ , • vx^ ■^' ' « -v . ' 0^ \f>^- ' % . ^ ^ * 1 *■ • % • . Pus from virulent abscess-formation. (Grawitz.) The leucocytes show marked necrotic changes, chromolysis. r, e, well-preserveJ leucocytes; E. K., connective-tissue cells from the neighboring granulations ; :, 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 suifer 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. 318 least resistance, until it is finally (li.scharjjjcil along with some of the bacteria and poisons. This frtMiuontly brings relief, and the abscess becomes an open wound, which heals by granulations in the way already outlined. In other cases the conflict between the bacteria and the tissues may be niopti evenly balanced and the pus confined by granulations, which arc 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 tiie 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 wdien the burrowing 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-Avall 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 membi'anes, the lung, etc. A case of lobar pneumonia may be selected as a typical example. After a preliminary congestion of the vessels in the walls of the pulmonary alveoli an exudate, consisting of serum and red cor- puscles, with a comparatively 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 meanwhile losing their coloring-matter, so that the red color due to them passes into a 314 HISTOLOGY OF THE MORBID PROCESSES. gray (Fig. 272, a). In favorable cases a stage of " resolution " fol- lows that of gray hepatization ; the fibrin disintegrates, and the exudate becomes softened (Fig. 272, h) and is expectorated. This is not the invariable outcome. Sometimes the fibrinous exudate is replaced by new-formed fibrous tissue, granulation-tissue, develop- ing from the alveolar walls, and the alveoli become obliterated. The process in that case is similar to that which affects the pleura. The pleural surface over the parts of the lung which are the seat of the pneumonia is usually also the seat of a similar inflammation ; but here the course of the process is a little different. There are fewer red blood-corpuscles and less serum in the first exudate that is formed, probably because the proximity of the bloodvessels to the pleural surface is less immediate than the corresponding rela- tions in the pulmonary tissue (Fig. 277). The exudate therefore Fig. 277. D E ■IWJ ^SiSi -/^ '^vi*:^*. «■,, ■'^:. ^Llli .^.-■'- a*' '^ ■' .• »A /-. :^7jf^/ ML i-y Exs Fibrinous pleurisy, ten hours after its inception. (Abramow.) Lg, lung, in which three alveoli are shown in section. These contain an exudate, consisting chiefly of red blood- corpuscles and fibrin in somewhat granular form. In the alveolar walls are capillaries containing either red corpuscles or leucocytes. 3IL, membrana limitans of the subendo- thelial areolar tissue; £, endothelium with nuclear chromolysis; F, fibrin; Ic, leuco- cytes; D, mass of red corpuscles, fibrin, and leucocytes, the latter with polymorphic nuclei; a, b, c, red corpuscles in various stages of decolorization and disintegration; D and F make up the exudate upon the pleural surface; £xs, exudate in the puhnonary alveoli. first appears as a layer of fibrin upon tlic 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 witli fibrous tissue. STRUCTURAL CHANGES DUE TO DAMAGE. 315 In this way a lihroiis thickening of tiu; pleura is formed, whicli remains as an en(hiring evidence of the inHammation 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 tibrin is formed on both pleural surfaces, which become agglutinated in case they are in contact. When, in such cases, the inter[)osed fibrin is rc[)laced by cicatricial tissue, per- manent iibi'ous adhesions between tiie lung and thoracic wall result. When the exudate contains sufficient serum to prevent the agglutina- tion of the two ])leural surfaces such adhesions do not take })lace, but each pleural surface receives a permanent layer of fibrous thickening. Fibrinous inflammation may afi'ect other tissues than those of the serous membranes (Figs. 278 and 279). Fig. 278. ,1. , ' «, .r 'i. j-v^'-i V* Fibrinous leptomeningitis: a, cerebral cortex; 6, 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 exndation 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; b, 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 ^vith 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 com])letely 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. ?,\1 surfaces. In the exudate, besides the usual constituents, there are desciuaniatcd epithelial cells and a variahle amount of mucus. Mucus, it will be remembered, is a substance normally secreted upon the mucous memlM-aiu's, where it serves to protect the underlying cells. When those luenibnines are irritated the supply of mucus is increased. In catarrhal iullanimatious it may be so abundant as to Fig. 280. W *^j^ ^>^ h — s it&^^H' m: /^^.'; s#V.. s^ ^J i'rf^ V Mii ^# ..U^ Serous leptomeningitis : a, cedematous fibrous tissue of the pia mater, the fibrous elements of the tissue being separated by the serous exudate ; b, group of leucoeytes, probably held together in part by fibrin; c, granular fibrin and detritus; b 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 scmietimes give the exudate an almost purulent appearance. 6. Croupous inflammation is an inflammation of a surface, char- 318 HISTOLOGY OF THE MORBID PROCESSES. acterized by the formation upon it of a " pseudomembrane " com- posed chiefly of fibrin. 7. Diphtheritic inflammation is a term usually applied to inflam- mation atfecting 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. Catarrhal bronchitis : n, areolar tissue of the siibmucosa, infiltrated with serum and leuco- cytes; b, alvecjlns of a mucous gland, infiltrated at the periphery by leucocytes. The epithelium is undergoing colliquative necrosis, and in the centre of the lumen are a few leucocytes with fibrin, c, c', bloodvessels, c' shows an infiltration of the wall by emi- grating leucocytes, d, muscularis mucoste ; 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 arc so acute that the epithelium is destroyed, instead of stimulated to the production of excessive mucus. formation of a meml)ranous 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 granuhitions, leaving an ulcer. 8. The "infective granulomata," such as tubercle, gumma, and the STRUCTURAL CHANGES DUE TO DAMAGE. 319 iio&»*? '^_?**3*V>. r Chronic interstitial inflammation. Early stage of productive interstitial neuritis. (Nau- werck and Barth.) The section is from the anterior root of a lumbar nerve. It repre- sents a number of apparently normal medullated nerve-fibres in cross-section, with proliferation of the cells of the endoneurium, as is evidenced by the abundance of nuclei in that tissue. result from the unusual strain brought upon the part of the heart which is deprived of the usual support of mu.scular tissue. It may be that other cases in which a loss of parenchyma is replaced by fibrous tissue are 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 offered. Further examples of interstitial inflammations are shown in Figs. 287 and 288. 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. Chronic interstitial myocarditis, late stage : a, dense fibrous tissue, the final result of the interstitial inflammation; 6, 6', b", atrophied cardiac muscle-cells; 6', vacuolation of a less atrophic coll ; h", section showing anastomotic branch joining two cells ; c, partially- obliterated bloodvessel. damentally the same, but susceptible of many variations ; and when the conditions are 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 suttice 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 hypenemia 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. ■■■■ ■>.■■; ,^-4^^- •• ■^'|;,^^'%fv Brown induration of the lung, the result of chronic passive cong:estion caused by valvular disease of the heart: a, small radicle of the pulmonary vein, dilated and filled with blood ; h, 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 ; (/, cavity of an alveolus ; c, 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 against 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 im})air tlic 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 hypersemias 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 extravasatecl 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 heematoidin ; or it may take the form of small granules of hsemo- 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 haemorrhages ; for the vessels necrosed are usually of small cahbre and surrounded by tissues sufficiently firm to check the flow of blood under the slight pressure within those vessels (Fig. 290). But more copious haemorrhages 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 wiiiU^ the wall of this vessel may become sufficiently destroyed to yield before the pressure of the blood within it ; ruj)ture may then take ])lace, with the effusion of considerable blood, liaMuoptysis. 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 trone far enou<>;h 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. "■- .-,••..•• • Haemorrhage in the kidney following general infection. (Tizzoni and Giovannini.) The htcmorrhage has taken place within the capsule of a Malpighian body and part of the extravasated blood has passed into the corresponding uriniferous tubule. Tlie glomer- ulus has been compressed (to the right), an occurrence which i)ro1)ably cliecked 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 columnjB carneae 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 iutima of a vessel or its mechanical destruction, as in the tvins; 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 thromboj)hlebitis 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. 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 brouglit 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 frngment, or a particle of tissue. With the exception of the branches of the portal vein, the vessels obstructed by an embolus are arterial. Th(^ 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 cmbohis is called a sopti(!, 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-Hirschfelrl.) 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 tliem dissolved. site of the original lesion, is induced by the bacteria brought with the embolus. If the original inflammation was suppurative, ab- Fio. 293. 6 Experimental ancemic infarction of the kidney ; rabbit. (Foa.) a, necrotic tissue formerly supplied by the artery obstructed ; b, zone of affected tissue surrounding the infVirct. 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 sulfer necrosis (Fig. 293). Such a mass of necrosed tissue is called an " infarct." Infarcts are divided into anaemic and hteraorrhagic 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. 294. Hsemorrhagic infarct of the lung. (Kaufmann.) The section contains a portion of the plugged vessel beyond the site of the embolus. It and the pulmonary alveoli are filled with blood, which, in the latter, has passed through the capillary walls, rendered per- vious by malnutrition. This blood 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 tlic ai)ility of leucocytes and other amceboid cells to incorporate within their cytoplasm ])articles 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 the.se 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 CHANGES DUE TO DAMAGE. 333 Phagocytes do incorporate bacteria ; but if those I)acteria are viru- lent, the phagocyte either refuses to take them witiiin its cytoplasm, or, after doing so, suffers degeneration or necrosis. It has no pecu- liar inuuunity against the action of the bacteria. On tlie other hand, it has been shown that the fluids of the body are capable of diminishing tlie 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- tinesis; A, B, D, with leucocytes, fragments of tissue, and red corpuscles in their cyto- plasm. those in the blood and lymph ; ^ bnt 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 eiFect 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 witli the necrosed portion, the dead tissue may l)e more or less completely replaced by tissue ' 'J'Jii; jiolynuclear neutropliile leucocytes are those which most frequently act as phagocytes. STRUCTURAL CHANGES DUE TO DAMAGE. 335 of new formation spriiifjjing from the living portion. If this takes place, the cells of the latter portion multiply and reassume those formative activities that they possessed during the develop- ment of the tissues in earlier life. The division of the cells al- ways tidvcs 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 Fi<;. 297 Fig. 298. f,|--a ^t$m m-b^^ .:ymmh. gf^,^/.tf Phases in the regeneration of the gastric mucous membrane; dog. (Griffini and Vassale.) a, regenerated columnar epithelial cells covering the base of the wound ; 6, c, karyokinetic figures indicative of proliferation. does not appear to take place. In Fig, 293, zone h, karyokinetic figures are seen in the renal epithelium ; but it is doubtful Avhcther they signify the beginning formation of new renal tissue to replace 336 HISTOLOGY OF THE MORBID PROCESSES. that killed in the anseraic 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 significance of that tendency. 1. Epithelium. — The regenerations of which epithelium is capable are very extensive and perfect. In some forms of epithelium — €. 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 STRUCTUHAL ('lIASdES Dl'E TO J) A MAGE. 337 !M(i :!M(i. 4 M--.^:^' ip. ^^ 3v^-- Kduee a highly cellular tissue, which devel- ops into tendinous fibrous tissue (Figs. 301, 302, and 303). 22 338 HISTOLOGY OF THE MORBID PROCESSES. 4. Bone. — Wlien a piece of boue dies fresh bone is produced through a rejuvenescence of the formative activities of the periosteum (or endosteura). While this new formation of bone is in progress tlie dead bone is removed by phagocj'tes, 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). Fig. 304. t\k 'f? nh t ff Ih •fc H III , Ik sp Regeneration of bone. (Barth.) nk, fragments of necrotic bone; rz, osteoclasts; o, osteo- blasts ; Ik, bone of new formation : y, bloodvessels ; nk', lamina of dead bone, (sp, acci- dental crack in the section.) 5. Cartilage. — This tissue is ca])ablc of only a limited and imper- fect regeneration. Defects in cartilage are usually made good by STRUCTURM. CIIANUKS DVK TO DAMAGE. P,39 the tlevel<)j)in(Mit of fibrous tissue, wliicli may become modified into adipose tissui', or by bone-production if the daniat^c; causes a re- juvenescence of pi'riosteuni or endosteuni. (). Smooth Muscular Tissue. — Non-striated niusele-cells are capa- ble of niMlli|)li('ation, but in infiaiumatory conditions the tissue of the media of the vessels does not appear to keep pace with that of the intiina in the j)ro(hu'tion 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 midtiply and occasion a hyperplasia of the tissue. This appears, however, to be in response to a functional demand, rather than one Fio. 305. Fif:. 306. Fis. m").— Karyokinctic figures in smooth muscular fibres. (Busnchi.) Fig. 306.— Kegenenition of a striated musele-fibre. (Kirby.) a, remains of the old contractile substance; b, rejuvenating cytoplasmic fragments, with their nuclei; r, similar fragment containing a bit of old contractile substance and a nucleus in karyokinesis. d. of the results of dama<2:e : a functional hyperplasia. Karyokinetic figures have been ob.served 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. — M'hen a striated muscle-fibre undergoes 340 HISTOLOGY OF TUB 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. KS KZ KB 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). Tiie cells of the neuroglia are, on the other hand, capable of regenerating that tissue. In this respect the neuroglia resembles the interstitial tissue of otiu^r organs than those of iha central nervous system, often increasing in amount when there is a diminution in the l)ulk 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 suif'ers 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 tlien existent. AVe attribute these phenomena to the force of heredity, but the expla- nation is incomj)lete, for that term merely expresses tlie 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 adajitation 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 usually 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 iu structural differen- tiation may l)e so^reat that the resulting; tuuior resetnhh's enihryonic tissue. Such tumors are eliuieally mali}i;uaut, 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 ditferentiation 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 aifecting 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 tmnor composed of bone may be produced Avithin 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 ])art 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 hypoderm. 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 MOBBID PBOCESSES. arranged in a manner usually quite unlike that of any normal organ. In consequence of the numerous variations in tissue-production M-hich 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. €., 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 by 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 malignancy, and is not always present, even when the patient has a very malig- nant fr»rm 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 Avliich 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 dencics. The gcMicnil character of the tissue composing it can be (letorniined ; an a{)[)r(>xiiiuite idea of the repnxhictive activity of the cells formed ; the tendency to invade or inKltrate the sur- ronnding 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 grow'th, 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 peculiarities 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 346 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, myxochondrofibroma, 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 " teratoniata," which contain structures simulating hair, teeth, bones, etc., arranged without definite order, and often TUMORS. 347 present in great numbers. Tlicy spring from the reproductive organs of the body, and ap[)ear to i)e erratic attempts at tlie pro- thiction of new imUvidnals. A new fr)rniation of bloodvessels accompanies the development of tumors, and these vessels are associated with a supporting con- nective tissue which may be conceived as a })art of tliis addition to the vascular system of the bitdy, rather than as an integral part of the tumor itself. Tliis 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. (Birc-h-Hirschfelil.) The dense fibrous tissue is in irregular nodules, between which are bands of less dense fibrous tissue containitig 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 oi)en meshwork, mIucIi 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. CEdema 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 fasciae, periosteum, Fig. 309. Dense form of fibroma. (Ribbert.) Section from a fibroma of the dura mater. The inter- celluhir 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. Dense form of fibroma. (Ribbert.) 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 have been omitted from the figure. etc., and those fibromata that occur in the uterus arc of similar character. They are usu;illy composed of nodular masses of dense TUMORS. 340 stniotiiro, which are hchl toj^othc-r by a more areolar fibrous tissue sui)iK»rtiii<,^ tlie hir^er bloodvessels of the tumor (Fi^. 308). Among tile hardest of the fibrous new-formations is the keloid, which in its oldest parts resembles (.!d cicatricial tissue, the fibrous inter- cellular sul)stance being comi)acted into dense, almost hom<»gencou.s 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 Fjg. 311. 6- — ^ * f ). > • I V X n1-^""^ f^*^ " \s'2^^^^ ;^ Intralobular fibroma of the breast. (Ziegler.) a, acini and ducts of the ^land; h, 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 interlohnlar form ; and, 2, the intralobuhir form, in which the individual acini of the gland arc separated and sur- rounded by bands of fibrous tissue (Fig. 31 1 ). These ditfu.se fibrom- 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 hsemotoxylin. 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. Tlie cells are less uniform in character and in size, are more irregularly distributed through the matrix, and are frequently embedded in the latter without an intervening capsule. The tumor is rarely comjiosed 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 pre-existent cartilage, bone, or TUMORS. J51 Fi(i. 312. ^^6 Lipoma of the kidney. (Birch-IIirschfeld.) The boundary between the adipose tissue of the tumor and the renal tissue Is not sharply defined. The former occupies the middle of the section and extends to its lower edge. fibrous tissue. When they apparently spring from hone their true origin may be from small remnants of cartilage which have escaped the normal ossification. m WMW^' 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 352 HISTOLOGY OF THE MORBID PROCESSES. Avith mucous and fibrous tissue, adenomatous new formations, or sarcoma (Fig. 313). Chondroniata 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. ^VA'X".-^ .^,^r^^^Xi-^J\Lt -.^'N-^'Wl^t Osteoid endochondroma. Section from a metatasbic 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 chondrorayxosarcoma. 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 reseml)ling the normal perichondrimn. Where there is an admixt- ure with cither sarcomatous or myxomatous tissues, these confer a malignant character upon the mixed tumor, and it is quite pos.si- TUMORS. 353 bio for fraf>;rncnts of cartilage to become detached from the primary growth and appear in the secondary tumors, shotdd metastasis occur. 4. Osteoma. — Tlie most important tumors containing bone are mixed tumors that an; significant chieHy because of their other (ionstituents. 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 Fi(i. :;io. 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 — r. r/., 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 lacunse are apt to vary in size, shaj)e, 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 s])indle-shape(l 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. 316. Section from a subcutaneous myxoma. (Birch-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 arc prepared after hardening, many of those processes will be cut in such a way that tlu'ir connections with the cells in the contiguous sections arc 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 jwint. 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 clefte). 356 HISTOLOGY OF THE MORBID PEO CESSES. Endotheliomata, on the other haud^ spring from the connective tis- sue;;, often at a point remote from any epithelial structures ; e. g., the dura mater. When the endothelioma owes its origin to a proliferation of the flat cells lining the lymph-spaces 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. 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, n, n, necrosed groups of endothelial cells ; h, h, 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 })e the scat of calcareous infil- tration. This is the origin of the ])samm()mata or " saud-tumors " of the cerebral membranes (Fig. 320). In other cases the cells may not acquire the membranous character of adult endotlielium, but continue to multiply witliout such specialization. Tlien the tumor partakes of the sarcomatous nature of the other connective-tissue tumors of higlily cellular structure and devoid of any marked TUMORS. Fig. 319. ^aotf \^^ ^r ft F 357 Endothelioma from the floor of the mouth. (Barth.) Section showing the advance of the growth into the lymph-spaces : o, 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 mul- FiG. 320. Early stages in the formation of a psaniinoina. (Ernst.) a, collection of endothelial cells; 6, 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 jjrowth. 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 M'ill serve to show that some members of that group closely simulate epi- theliomata in their structure, though they are quite diflPerent in their Fig. 321. Endothelioma of the ulna. (Driessen.) a, a, alveoli lined with endothelial cells and occupied by blood; 6, areolar tissue between the alveoli, containing capillary vessels, c; (/.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 tlie tumor itself. Fig. 822. W -0f ^^^*^i^ "A^ m 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 Fig. 323. fv f^±^k.. ~^, -^^' Endothelioma of the thyroid. (Limacher.) 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 cases 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 Mdiicli 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 gi'eatcr 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 jiroduc- 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 j)arts 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. Tiiis argiuuent is borne out by the results of experience. The sarcomata might be arranged in a series according to their roliferation 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 hsemangiomata, 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. Hsemangioma. — 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 (nsevi) 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 raccmosa), for in this case there is a real reproduction or growth of the vessels. TUMORS. 375 AniriosarcoiiKita are tumors in which a now 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 Cavernous hsemangioma of the liver, a, siinstance of the liver; 6, 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, Tliis 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 376 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 hagmangiomata 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. When 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 mucosae and develoj) abundantly in the submucous coat or even in the deeper, muscular tissues of that part of the in- testine. TUMORS. 377 The adenomata of tlie breast deserve a rather close study. A perfectly simple adenoma of this gland appears to be a very rare growth. Tiu-re is nearly always an association with dilfnse 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. 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 it.self. 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.^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 groM'n 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 surroundino^ an isolated mass of fibrous tissue if the section does not include the pedicle of that particular ingrowth (Fig. 342). Fig. 341. i Adenofibroma of the breast. (Birch-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 brca.'^t witli a view to determining TUMORS. 379 Intracanalicular adenofibroma of the breast. (Kaufmann.) the acini have not been obliterated, and a correct iiiterj sents no difficulty. (Kaufmann.) In this example the lumina of correct interpretation of the appearances pre- FiG. 343. Section from the mammary gland of a nullipara, aged eighteen ; moderately magnified. (Altmann.) 380 HISTOLOGY OF THE 31 ORB ID 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 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 tlie 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 Ijcing in an undeveloped state. Figs. 347 and 348 show sections of the nuunniary gland of a Section from the mammary gland of a nullipara, aged twenty-two ; more highly magnified. (Altmann.) woman, aged thirty -eight, who had horn 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. (.\ltmann.) 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 HISTOLOGY OF THE MORBID PROCESSES. structure of each individual tumor must be carefully weighed before a conclusion as 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. Section of the mammary gland in a state of involution. (Altmann.) From a woman, aged twenty-live, 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. 38.' first appears as little solid columns of opitlielial cells, which spring from the epithelium eoverinsj; tht; part anil penetrate the underlying Fig. 350. Section of mammary gland in a state of involution, (.\ltmann.) 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- Infiltratlng adenoma of the rectum, ninnseinann.i The tiirnre represents alveoli of atypical character, ditfering srreatly from the normal iilanduliir 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. a. Medullary carcinomata (Fig. 352) are those in which Fig. 352, 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 virtually 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 {::reatly preponderate over the epitheliut)i that there is a possibility of mistaking the tumor for a simple fibroma. Fi(i. 353. ^^^4^^^ ..^ s^l^ ^ X . C^ l,l| Carcinoma simplex mammoe. (Kaufmann.1 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 the.se carcinomata with the intracanalicular adenofibromata already de.seribed. 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, n. there is no ingrowth of fibrous tissue into the alveoli, as in the ca.se of the adenofibroma. The development of the fibrous ti.ssue 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 grow. 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 Fig. 355. Carcinoma invading adipose tissue. The figure represents a section of the fat surrounding the breast in a case of mammary carcinoma. Masses 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 (inflammatoryj 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 tlie lym[)li-currcnt for a greater or less distance from the original tumor, to find lodgement in some situation in which the conditions may be favorable for tlieir continued multiplication TUMORS. 387 (Fig. 355). The connective tissue of the new site is tiien 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-nodo, giving rise, if they multiply', Fui. ."56. 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 medullarv car- cinoma. The distinction between the diiferent 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 j)robably 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. (Ribbert.) The section represents a delicate stroma of areolar tissue separating alveoli, which are not filled 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 })c so extensive as to destroy 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 tlie 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. Via. 358. 389 '^^ .m^m>!k I V '^y$ '.ajjA \: -.-^ ^, 'J •' r Adenocarcinoma of the liver, (w Ilcukelon.) a, normal liver-cell: h, modified epithelial cell enteriiii? into the formation of the ncojiliism: c, normal nucleus; v:i[)(irati()ii and also favor the foniuition of" hiihhlcs in IIk; collo- dion. iVf'tor an interval of" one or more day.s tlu; colhjdion will have a jiclatinons consistency. Jt slionld he allowed to heconio 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. al(H)hol so that the whole of the inner dish is submerged. By the next day the collodion will be hard enough for removal f"r()m 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 i)reserve 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 ])er 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 dav after the specimen has been affixed to the glass block. These blocks, with attached specimens, may be preserved indefinitelv 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 })lane 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 41-1 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 rajjidly 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 by 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 maiu 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 seetions from fresh or hardened tissues by free-himd ciittin<^ 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 surfaee should be ground flat. In stro|)ping the razor, or niierotome-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 shoidd 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 l)e 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 upjDer 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, Avith 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 j);u;iniii being too hard. In tluit case the cutting should be done in a warmer room. This rolling will, however, cause little trouble in tiie use of the sections unless it be desired to have them adhere to each other at the edges to form ribbons, in which the suc(;essiou 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 Maver's albumin mixture, prepared as follows : beat up the Avhite of an Ggg 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 u})on 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 surfiice. 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. Hsematoxylin and Eosin. — Hsematoxylin, 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 may be preceded or followed by the employment of a counterstain with some diffuse color not affecting the nuclei. For counterstaining, eosin or neutral carmine is usually employed. Both stain tlie 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- 1 gram. 10 cc. 20 grams, 200 cc. METHODS OF STAINING. 419 toxylin, l)iit that devised Ijy Bohmer will iiiiswcr all purposes, and is verj' simple : 1. I Iiematoxylin crystals, Absolute alcohol, 2. Alum, Distilled water, 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-hfematoxylin require an interval of time for " ripening," and their staining-powers improve with age. Alum-htematoxylin 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 hfematoxylin : Transfer the sections from the 80 per cent, alcohol in which they have been kept to a dish of distilled water. At first thev "vvill float on the surface of the water ; this is a favorable moment for removing all folds and wrinkles. The sections should be manipulated with ]ilatinum 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 h?ematoxvlin into a watch-g-lass 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-powers 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 clearci' 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 ST AI SING. 421 bottom of the dish, and the sections to be stiiined are transferred from distilled water to the dye and distributed upon the paper in such a way that they do not lie over eaeh other. The dye acts very slowlv, twenty-four hours beinn of, 300 eosinophilic, \'1(\ larj^e inononiR'ieiir, 125 I)olyiiii('iear neutrophilic, 125 Lieberkiihn, crypts of, 139 Lipoma, 350 Liver, 146 cirriiosis of, 323 functions of, 151 lobules of, 147 Lobar pneumonia, 313 Lunj;, functions of, 173 gray hepatization of, 313 infundibula of, 171 red iiepatization of, 313 Lymph, 122 -nodes, 114 Lymphadenoid tissue, 76 Lymphatic glands, 114 Ijympbatics, 114 Lympho-angioma, 376 Lymphocytes, 125 Lympho-sarcoma, 363 MACERATION, methods of, 438 alcohol, 438 ciiromic 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, 3G9 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 Moiniting, methods of, 429 { anada-balsam, 428, 430 Dammar, 428 glycerin, 430 glycerin- jelly, 431 Movement, IJrownian, 29 amoeboid, 29 Mucoid marrow, 119 Mucous degeneration, 277 tissue, 74 Mucus, 278 Mil Her, cells of, 262 Mailer's fluid, 403 Muscular tissues, 83 tumors, 370 Muscle, cardiac, 89 regeneration of, 340 involuntary, 88, 91 smooth, 83 fiuiction of, 88 regeneration of, 339 striated, 91 regeneration of, 340 Myelin, 97, 98 Myelocytes, 119 Myxoedema, 183 Myxoma, 353 MAILS, 201 li Necrosis, 293 coagulation-, 294 liquefaction, 295 of nucleus, 294 Nephritis, acute parenchymatous, 272 Nerve-cells, 95 degeneration of, 283 -fibres, 96 -terminations, 103 Nervous system, 234 tissues, 94 regeneration of, 340 Neurilemma, 97 Neurite, 234 Neuroglia, 101 Neurons, 234 Nodes of Ranvier, 98 Nucleolus, 29, 33 Nucleus, 29 necrosis of, 294 structure of, 33 rnsoPHAGUs, 134 Uj 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 Ovarv, 207 Oviilii Nabothi, 216 Ovum, 20 maturation of, 217 PACINIAN bodies, 252 Pancreas, 142 Papilloma, 394 Parafiin, 409, 413 Paratbyroids, 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 _ Periciiondrium, 65 Perineurium, 100 Periosteum, 71 Peyer's patciies, 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 Pseudopndium, 29 Pseudo-stomata, 47 Pulinonarv alveoli, 171 Purkinje, cells of, 243 Pus, 312 Pyloric glands, 136 Pyogenic membrane, 313 r)ANVlP:R, nodesof, 98 \) Razor, stropping, 415 Reaction, micrcjchemical, 436 Rectum, 142 Red corpuscles, 1 23 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 Sfjermatids, 227 Spermatocytes, 227 Spermatogonia, 227 Spermatozoa, 231 Spinal cord, 236 association-fibres of, 239 collateral fibres of, 239 INDEX. 447 Spindle, achromatic, 37 Spiiulle-celi sarcoma, 305 Spirem, formation of, 35 Spirem-phase of karyokinesis, 35 Spleen, 170 Malpigliian bodies of, 177 Spongioblasts, 2(>'J Spongioplasm,"'29 Sputa, elastic fibres in, 438 tubercle-bacilli in, 433 Staining:, methods of, 418 carmine, alum-, 421 borax-, 421 lithio-, 4-21 neutral, 420 eosin, 420 fuchsin, carbol-, 423 gentian-violet, 423 Golgi's methods, 427 Gram's solution, 424 haematoxvlin, 418 iron-luematoxvlin, 425 methylene-bliie. 422, 423 Pal's" method, 426 Van Giesen's stain, 425 Stasis, intlammatorv, 298 Starch, tests for, 436 Stellate cells, 245 large, 245 small, 245 Stomach, 134 Stomata, 46 pseudo-, 47 Stratum granulosnm, 198 lucidiutn, 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 retina, 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 fatty, 436 Tests for haemoglobin, 436 iron, 437 phosphates, earthy, 436 starch, 436 Tissue, adipose, 78 areolar, 76 cicatricial, 308 connective, 63 elementary, 41 recogniliun of, 43 erectile, 222 fibrous, 72 fixation of, 401 fixed elements of, 303 granulation-, 304 lym[)hadenoid, 76 mucous, 74 muscidar, 83 necrosed, fate of, 295 nervous, 94 Tissues, cardiac muscular, 89 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 ThVroid sland, 181 Thvro-iodine, 184 Tongue, 129 Tonsils, 143 Touch, 252 Trachea, ItJS Transitional epitlielinni, 56 Tubercle, 320 -bacilli, detection of, 433 Tubercular ulcer, 322 Tuberculosis, 319 Tubes, I'^allopian, 210 of Henle, 155 Tumors, 341 angiomatous, 373 hemangioma, 374 lympliangioraa, 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 epitlieiial, 376 adenoma, 376 adeno-libroma, 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 T7ACU0LES, 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 Cntnloguc of Books PUBLISHED BY Lea Brothers & Company, 706, 708 & 710 Sansom St., Philadelphia. 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Philadelphia, 706, 708 and 710 Sansom St.— New York, 111 Fifth Ave. (cor. 18th St.). LEA BROTHERS & CO:S PUBLICATIONS. EDES (ROBERT T.). TEXT-BOOK OF THERAPEUTICS AND MATERIA MEDIC A. In one 8vo. volume of 544 pages. Cloth, $3.50; leather, $4.50. EDIS (ARTHUR W.). DISEASES OF WOMEN. A Manual for Students and Practitioners. In one handsome 8vo. volume of 576 pages, with 148 engravings. Cloth, §3 ; leather, $4. EGBERT (SENECA). HYGIENE AND SANITATION. In one 12mo. volume of 359 pages, with 63 illustrations. Just ready. Cloth, $2.25, net. ELLIS (aEORGE VINER). DEMONSTRATIONS IN ANATOMY. Being a Guide to the Knowledge of the Human Body by Dissection. From the eighth and revised English edition. Octavo, 716 pages, with 249 engravings. Cloth, $4.25 ; leather, $5.25. EMMET (THOMAS ADDIS). THE PRINCIPLES AND PRACTICE OF G YN^COLOGY. For the use of Students and Practitioners. Third edition, enlarged and revised. Svo. of 880 pages, with 150 original engravings. Cloth, |5 ; leather, $6. 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In one very handsome octavo volume of 238 pages, with 25 engravings and 8 full-page platen. Cloth, $2. FULLER (HENRY). ON DISEASES OF THE L UNGS AND AIR-PASSAGES. Their Pathology, Physical Diagnosis, Symptoms and Treatment. From second English edition. In one 8vo. volume of 475 pages. Cloth, $3.50. GANT (FREDERICK JAMES). THE STUDENT'S SURGERY. AMultumin Parvo. In one sc^uare octavo volume of 845 pages, with 159 engravings. Cloth, $3.75. GERRISH (FREDERIC H.). A TEXT-BOOK OF ANATOMY. By American Authors. Edited by Fkederic H. Gerrish, M.D. In one imp. octavo volume, richly illustrated. Preparing. GIBBES (HENEAGE). PRACTICAL PATHOLOGY AND MORBID HIS- TO LOG Y. Octavo of 314 pages, with 60 illustrations, mostly photographic. Cloth, $2.75. GIBNEY (V. P.). ORTHOPEDIC SURGERY. For the use of Practitioners and Students. In one Svo. volume profusely illustrated. Preparing. GOULD (A. PEARCE). SURGICAL DIAGNOSIS. In one 12mo. volume of 589 pages. Cloth, $2. See Students' Series of Manuals, page 14. GRAY (HENRY). ANATOMY, DESCRIPTIVE AND SURGICAL. New- American edition of 1897, thoroughly revised. In one imperial octavo volume of 1239 pages, with 772 large and elaborate engravings. Price with illustrations in colors, cloth, $7 ; leather, $8. Price, with illustrations in black, cloth, $6 ; leather, $7. GRAY (LANDON CARTER). A TREATISE ON NERVOUS AND MENTAL DISEASES. For Students and Practitioners of Medicine. Second edition. In one handsome octavo volume of 728 pages, with 172 engravings and 3 colored plates. Cloth, $4.75; leather, $5 75. GREEN (T. HENRY). AN INTRODUCTION TO PATHOLOGY AND MOR- BID ANATOMY. New (8th) American from eighth and revised English edition. Oct. 595 pages, with 215 engravings and a colored plate. Cloth, $2.50, net. Just Ready. GREENE (WILLIAM H.). A MANUAL OF MEDICAL CHEMISTRY. For the Use of Students. Based upon Bowman's Medical Chetnistry. In one 12mo. volume of 310 pages, with 74 illustrations. Cloth, $1.75. GROSS (SAMUEL D.). A PRACTICAL TREATISE ON THE DISEASES, INJURIES AND MALFORMATIONS OF THE URINARY BLADDER, THE PROSTATE GLAND AND THE URETHRA. Third edition, revised by S-VMUEL W. Gross, M.D. Octavo of 574 pages, with 170 illustrations. Cloth, $4.50. HABERSHON (S. 0.). ON THE DISEASES OF THE ABDOMEN comprising those of the Stomach, (Esophagus, Caecum, Intestines and Peritoneum. Second Amer- ican from the third English edition. In one octavo volume of 554 pages, with 11 engrav- ings. Cloth, $3.50. HAMILTON ( ALLAN McLANE ) . NER VO US DISEASES, THEIR DESCRIP- TION AND TREATMENT. Second and j-evised edition. In one octavo volume of 598 pages, with 72 engravings. Cloth, $4. HAMILTON (FRANK H.). A PRACTICAL TREATISE ON FRACTURES AND DISLOCATIONS. Eighth edition, revised and edited by Stephen Smith, A.M., M.D. In one handsome octavo volume of 832 pages, mth 507 engravings. Cloth, $5.50; leather, $6.50. HARD AW AY (W. A.). MANUAL OF SKIN DISEASES. New (2d) edition. 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In four large octavo volumes comprising 4600 pages, with 476 engravings. Vol. IV., now ready. Eegular price. Vol. IV., cloth, $6 ; leather, |7 ; half Russia, §8. Price Vol. IV. to former or new subscribers to complete work, cloth, $5 ; leather, §6 ; half Russia, $7. Complete work, cloth, $20 ; leather, $24 ; half Russia, $28. For sale by subscription only. Full prospectus free on application to the Publishers. HARTSHORNE (HENRY). ESSENTIALS OF THE PRINCIPLES AND PRACTICE OF MEDICINE. Fifth edition. In one 12mo. volume, 669 pages, with 144 engravings. Cloth, $2. 75 ; half bound, $3. A HANDBOOK OF ANATOMY AND PHYSIOLOGY. In one 12mo. volume of 310 pages, with 220 engravings. Cloth, $1.75. A CONSPECTUS OF THE MEDICAL SCIENCES. Comprising Manuals of Anatomy, Physiology, Chemistry, Materia Medica, Practice of Medicine, Surgery and Obstetrics. Second edition. In one royal 12mo. volume of 1028 pages, with 477 illus- trations. Cloth, $4. 25 ; leather, $5. HAYDEN (JAMES R.). 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