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Entered according to Act of Congress in the year 1898, by 


in the OflSce of the Librarian of Congress, at Washington. All rights reserved. 




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 

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 



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 

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<dhologiHche Anatomic. The student is also 
referred to Mallory and Wright's Pathological Technique, Lee's Mi- 
crotomist's Vade 3Iecum, and to the more recent German revised 
edition, Grundzurje der miJcroskopischeu Technik, by Lee and Mayer. 
It may be that well-founded exceptions will be taken to some of 
the explanations of morbid processes which are here offered ; but 
it is the author's hope that he has not advanced theoretical views 
with sufficient emphasis to mislead the student. Should the general 
plan of the work meet with a kindly reception, it will be his 
endeavor to c«)rrect, in a future edition, such errors and omissions 
as mav be revealed bv friendly criticism. 

E. K. D. 

New Ycjuk, Octolier, l.S!)8. 






chaptp:r II. 






















































During life all parts of the human body are the seat of constant 
activity. This is a fact too readily overlooked by the student who 
gains his knowledge of the structures of the body by a study of the 
tissues after death. To make that study of use to him in his medi- 
cal thinking he should constantly bear in mind that he is viewing 
the mechanism of the body Avhile it is at rest, and, furthermore, 
that the methods emj)loyed in the study of the minute structure of 
the parts not only arrest the normal activities of those parts, but 
€xpose them to mutilation. He must, therefore, constantly supple- 
ment the knowledge of structure he gains by his histological studies 
by recalling to mind and applying that which he has acquired by 
a study of physiology, habitually associating his ideas of structure 
and functional activity, until he can hardly think of what a struct- 
ure is without at once recalling what it does. This he cannot do 
till he has mastered at least the general outlines of systematic 
anatomy and of physiology. Those two fundamental subjects are 
brought together by an intelligent study of the minute structure of 
the body, histology, which, for this reason, has also and appro- 
priately been called physiological anatomy. 

But the student of medicine must go beyond this. To the con- 
ception of the body during health, which he has formed by this 
thoughtful method, he must then add a conception of the influence 
exerted, both on the structure and activities of the body, by ab- 
normal conditions which disturb or thwart the usual working of 
that complex mechanism. The more closely he can make those 
conceptions agree with observed facts, the more perfect will become 
his ability to interpret the physical signs and symptoms of disease, 

2 17 


and the clearer will grow his insight into the causes and tendencies 
of the processes of which they are an expression. 

In all his studies he must seek not merely to train his powers 
of observ^ation ; he must endeavor to cultivate his ability to inter- 
pret what he sees ; to deduce the processes and causes that have 
wrought the results he perceives, and to compare those deductions 
with the conceptions of living things he has already formed, so that 
his ideas may remain in perfect accord with one another as his grasp 
of the subject enlarges. By so doing he may hope to create a life- 
like mental picture of the body both in health and during disease. 

The activities of the body involve changes in the substances of 
which it is composed. Some of these changes are always destruc- 
tive in character — that is, they result in chemical rearrangements 
which convert more complex combinations of less stable nature into 
simpler combinations of greater stability. Such chemical changes, 
whether they take place within the body or in external nature, 
among organic or inorganic substances, are always accompanied by 
a liberation of energy hitherto locked up or stored in latent or 
potential form in the compounds of higher complexity. It is this 
liberated or kinetic energy which is utilized by the bodily mechan- 
ism for the performance of internal or external work. When 
directed in various ways and operating through diiferent structures, 
this energy occasions visible movement, appears as heat, etc., or 
passes again into the latent form in the elaboration of more com- 
plex chemical substances from those of simpler constitution. 

These associated transformations of matter and energy involve a 
continual loss to the bodily economy. The stock of energy is dim- 
inished during the execution of external work and by the dissipa- 
tion of heat. The store of usefid chemical substances is reduced 
by their progressive conversion into compounds that are insuscep- 
tible of further utilization, and which, in many cases, may act injuri- 
ously upon the structures of the body. Under normal conditions 
such substances are eliminatcid from the body. 

It is evident, then, that the body is constantly suffering a loss of 
both energy and matter. This loss must be made good if the 
activities of the body are to be maintained, and this is accomplished, 
during health, through the absorption of fresh material, containing 
lut(!nt energy, from the food taken into the body. 

The activities of the body are not the same in all its parts. They 
arc all alike in one particular — namely, that each part must main- 


tain its own nutrition, incorporatinii; the food-materials that are 
accessible to it and iisint]:; them in such a way as to keep its struct- 
ure in a normal 4^ondition. But, aside from this duty which is com- 
mon to all, each ])art has a duty to perform for the fjood of the 
whole or<;anism ; and, as we shall see, this duty often appears to be 
paramount, the activities which it necessitates being carried on 
even if they involve a sacrifice in the nutrition or structure of the 
individual part. 

Each part of tlu> 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- 


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 

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 



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.) 


s are derived from tlio.«e of the primitive ectoderm, but the 


])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. 


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 



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 ; </, alimentary canal, not yet completely closed * *, passes 
through the external layer of the mesoderm to its inner surface ; e, deutoplasm, or yolk 
of egg. 

some of the connective tissues, although one develops from the 
ectoderm and the other from the mesoderm ; and the orano-lion cells 
of the central nervous system differ greatly in structure from the 
epithelium of the skin, nails, etc., and the cells of the neuroglia, 
notwithstanding the fact that they all spring from the cells of the 
ectoderm. The explanation is to be sought in the similarity of the 
usefulness of neuroglia and connective tissue and the difference in 
the functions of ganglion cells and those of the other tissues eman- 
ating from the ectoderm. 

During the early stages of development the cells of the germinal 
layers are very similar in character, although, as m'c have seen, 
their potential qualities are quite diverse. As growth proceeds, 
they begin to vary in size, shape, and internal structure in the dif- 


fercnt parts of the foetus. Their relative positions become modi- 
fied. The primitive organs are defined and the tissues of which 
they are composed become elaborated. 

The elaboration of the tissues is wrought by the cells, which dis- 
play what is called their formative powers in the production of 
materials of various sorts which lie between them, and are called 
the intercellular substances. The amount and kind of intercellular 
substance vary, each form of tissue having its own peculiarities in 
this respect, dependent upon the role it is to play in the general 
economy. Some of the tissues perform functions which require the 
active processes that can be carried on only in cells, and in these 
the intercellular substances are either small in amount and appar- 
ently structureless, as in epithelium, or their place is taken by a 
tissue of separate origin, while the cells, relieved of the necessity 
for exercising their formative powers in this direction, become 
highly specialized to meet the functional demands imposed upon 
them. This development is met with in the muscular and nervous 

Other tissues of the body are of use mainly because of their 
physical properties, such as rigidity, elasticity, tensile strength, plia- 
bility, etc. These tissues, collectively called the connective tissues, 
are essentially passive. They require little or no cellular activity 
for the performance of their functions, and it is in the elaboration 
of these tissues that the cells exercise their most marked formative 
powers during the development of the body, causing the deposition 
of intercellular substances which possess the requisite physical char- 
acters — rigidity and elasticity in the case of bone, pliability and ten- 
sile strength in the case of ligamentous structures, etc. As these 
substances are perfected, the cells decrease in activity, until they 
merely preside over the integrity of the intercellular substances they 
have already produced. 

It may be well to point out here a distinction that divides the 
tissues of active cellular function into two groups. The first group, 
including the various modifications of epithelium, displays its ac- 
tivity in the elaboration of material products, taking the form of 
either new cells which are continually being produced, or of certain 
chemical substances which appear as a secretion. The second 
group, comprising the muscular and nervous tissues, exercises its 
functional activities in the storage of latent energy in such sub- 
stances of unstable chemical nature and in such a manner that it 


can be liberated wlieii recjiured and directed towartl the accomplish- 
ment of some definite purpose. The functions of both groups 
require an acj^ive intracellular metabolism, resulting in the forma- 
tion of particular chemical substances. In this they are alike. 
But in the first group the production of those substances is, in 
itself, the functional purpose of the process, while in the second 
group those substances are merely a means for holding energy in 
the latent condition. If we may so express ourselves, the first 
group utilizes energy for the elaboration of material, the second 
group elaborates material for the utilization of energy. 

In the adult, under normal conditions, each kind of cell, if it 
reproduce at all, gives rise to cells only of its own kind. But when 
the conditions are morbid, a sort of reversion may take place, the 
progeny of a given cell then showing less evidence of specialization 
than the parent cell. Such reverted cells, or their descendants, may 
never develop into more specialized cells, or they may regain the 
original degree of specialization possessed by the first cell, or, fin- 
ally, they may become specialized along some divergent line of devel- 
opment, giving rise to a tissue that is nearly or remotely akin to 
that from which they started, according to the degree of reversion 
which has taken place. The reversion appears never to extend 
further back than the degree of specialization that is marked by 
the formation of the three embryonic layers in the history of devel- 
opment ; for example, epithelium which springs from either the 
entoderm or ectoderm does not revert to a primitive condition from 
which it can develop into bone or some other form of connective 
tissue normally derived from the mesoderm. Examples of rever- 
sion will be met with in the chapters on Inflammation, Tumors, and 



As has been stated in the introductory chapter, the cells of the 
body are not all alike. Most of them have undergone modifications 
fitting them for the performance of some definite function, and the 
majority of them are in consequence not appropriate objects for a 
study of the general characters of a cell. The extent to which this 
modification has affected the visible structure of the cell is, how- 
ever, very different in the different tissues, and in some of them the 
cells retain so much of their original embryonic appearance as to 
closely resemble the unspecialized cell. 

This is true of the cells of some varieties of epithelium. But, 
though in appearance they give little evidence of specialization, in 
their functional activities they display very marked modifications of 
the powers of the jyrimitive cell. Some of those powers, perhaps 
the nutritive, perhaps the secretory, have become exaggerated, while 
others, e. g., the locomotors/, or reproductive, have fallen into abey- 
ance, or suffered almost total extinction. 

On the other hand, it is obvious that such cells as constitute the 
whole body of unicellular animals must retain all the powers essen- 
tial to a living cell in relatively equal states of development. No 
one of them can be extinguished or thrown out of its proper bal- 
ance with respect to the others if the cell is to remain normal. 
And yet, even among the unicellular organisms, certain parts of the 
cell may be very evidently specialized for the performance of par- 
ticular functions. For example, the cilia of infusoria have the 
power of executing much more rapid movements than the other 




parts of the same cell. And it is probable that all protozoa, ^. e. 
unicellular animals, possess similar, though less obvious and in- 
ternal, heterogeneity of constitution. 

The less the degree of specialization or differentiation in the 
structure of an organism, the less highly developed is the functional 
activity of which it is capable, and the less perfect its ability to 
cope with possible unfavorable environment. The value to the 
whole organism of a diversity in its parts is, therefore, unquestion- 
able, and the higher we go in the animal kingdom, the greater we 
find the development of this diversity, coupled with a more and 
more perfectly adjusted co-operative interdependence of the differ- 
ent parts of the body. 

In the protozoa the single cell does all the work of the whole 
organism. In the multicellular animals, the metazoa, this work is 
distributed among the component cells of the body, each of which 
has developed an efficiency for performing its special work that 
would be incompatible with a wider range of duties. 

It is quite impossible to find in nature any example of a cell 
devoid of all individual peculiarities attributable to differentiation 
or specialization. We must, therefore, study several varieties of 

Fig. 6. 

Amceba pellucida. (Frenzcl.) a, ectoplasm ; b, endoplasm ; c, nucleus ; d, nucleolus ; e, large 
contractile vacuole ; /, incorporated foreign body ; g, g, pseudopodia. 

cell in order to gain an ideal conception of such a cell. This accom- 
plished, we may consider those cells Avhich occur in nature as special 
modifications of that type. 

Perhaps the simplest cell leading an independent existence is the 
protozoon, amoeba (Fig. 6). This animal is widely distributed in 


moist oarth, upon tlic surfaces of a(|uatic plants, and in the soil at 
the margins of ponds and sluggish streams. 

The body ef the ama3ba consists of a gelatinoid substance wliich 
has received the name protoplasm, or, more definitely, cytoplasm. 
Within this cytoplasm and sharply defined from it is a round or 
oval, vesicular body, called the nucleus, Avhich in turn contains one 
or more particularly conspicuous granules, the nucleoli. 

The most superficial layer of the cytoplasm appears perfectly 
clear, colorless, and homogeneous. It envelops the rest of the cyto- 
plasm, which has a granular appearance. The clear peripheral 
portion is distinguished as the "hyaloplasm," or "ectoplasm ;" the 
granular internal portion as " spongioplasm," or "endoplasm." 
The terms hyaloplasm and spongioplasm are also used in a different 
and more restricted sense, as will presently appear. 

When viewed under the microscope, the granules of the cyto- 
plasm are seen to possess a constant, slight, vibratile motion, the 
Brownian movement, to which is added now and then a flowing 
movement from one part of the cell to another. At intervals there 
is a protrusion of the ectoplasm at some point, extending for some 
distance from the body of the cell, a pseudopodium. This may soon 
be retracted again, merging with the rest of the ectoplasm, or some 
of the endoplasm may flow into the central portion of the pseudo- 
podium, converting it into a broad extension of the cell-bod3\ This 
may subsequently be withdrawn, or the whole mass of cytoplasm, 
with the nucleus, may flow into the pseudopodium, gradually in- 
creasing its size, until the whole cell occupies the original site of the 
pseudopodium. In this way the animal executes a slow, creeping 

These pseudopodial movements and the locomotion occasionally 
incident to them appear to be wholly spontaneous, i. e. dependent 
upon internal conditions of wliich wc have no knowledge. They 
may, however, be influenced by external circumstances. Certain sub- 
stances evidently attract the amoeba, others are either matters of in- 
difference to it or repel it. If a pseudopodium comes in contact with 
some particle in the surrounding medium, it may retreat from it, 
appear indifferent to it, or be attracted and proceed to incorporate 
it. This is accomplished by the cytoplasm flowing around the for- 
eign body and coalescing on its further side so as to enclose it. It 
is then conveyed to the body of the cell, either by cytoplasmic cur- 
rents, by the withdrawal of the pseudopodium containing it, or 


by the streaming of the cell-body into that protrusion. The 
fate of the particle thus incorporated dejjends upon its nature. 
If it be serviceable as food, it is gradually digested and ab- 
sorbed, or such parts of it as are digestible are so utilized, and 
the remainder, no longer of use to the amoeba, is extruded from 
its body. 

These phenomena reveal powers of perception and selection on 
the ]>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 

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 

Eventually the amoeba reproduces its kind by dividing into two 
similar cells, eacli of which grows into a likeness to the parent 

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. 



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. 


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 


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. 


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- 


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. 


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 

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 



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. 



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 that have 
already been described as radiating from the polar bodies, but of 
even greater prominence. They are arranged to form a spindle 



■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 

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 

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<lually becomes deeper and 
finally severs the two portions ; or a series of punctiform or short 



linear cnlai'i:;('mcnts of the lines of the achromatic spindle appear 
in its equator, and thn»M<;h these a plane of cleavage, dividing the 
two new eells^froni each otlier, is finally established. 

It is rarely that any l)iol()gieal process assumes such mathemat- 
ical [)rccision as is displayed in karyokinesis. The purpose of that 
mode of cell-division a})pears to be an exactly equal partition of 
all parts of the chromoplasm between the young cells. Whether 
the amount of cytoplasm given to the daughter-cells is the same 
or different, the division of the chromoj)lasm is exactly equal, not 
only in its whole bulk, but each chromosome, which appears to be 
the morphological unit of the chromoplasm, is split into exactly 
eipiivalent halves, one of which is contrll)uted to the formation of 
each daughter-nucleus. It is for this reason that the chromoplasm 
is looked upon as the carrier of hereditary peculiarities. 

After the formation of the daugiiter-nuclei, the centrosome 
usually passes from it into the cytoplasm. It may divide earlier 
than has been described, the division taking place while it exists 
as the polar body, or even earlier (Fig. 16). 

A cell nearly always divides to form two new cells, but some- 
times three or more cells may be produced, the chromosomes being 
distributed among them (Fig. 19). Such cases are probably 

Fig. 19. 

Epithelial cell from a carcinoma. (Galeotti.) The centrosome has divided into four portions, 
and the chromosomes are arranged with reference to these. The figure represents the meta- 
kinetic phase of karyokinesis, which will result in the formation of four imperfect 

always morbid, and the resulting cells are not wholly the equiv- 
alents of the parent cell. 

It occasionally happens that the cytoplasm fiiils to divide after 
the formation of the daughter-nuclei, and cells with two or more 
nuclei result. When the nuclei continue to multiply and the 



cytoplasm increases in amount, l)ut does not suffer division, large 
multinucleated cells are produced, Avhich have been called " giant- 
cells." They occur normally in the marrow of bone and are pro- 
duced in many of the inflammatory processes. 

The direct or amitotic method of cell-division is inaugurated by 
an active change in the shape of the nucleus, which may have pre- 
viously increased in size and become richer in chromoplasm. The 
nucleus becomes constricted and finally separated into two portions, 
which are not necessarily equally rich in chromoplasm. The cyto- 
plasm, either at the same time or later, becomes similarly con- 
stricted until it is divided into two parts, each containing one of 
the nuclear divisions (Figs. 20, 21, 22). 

Fto. 2(1 

Fig. 21. 

Fig. 22. 

Amitotic cell-division. (Flemming.) Epithelial cells from the bladder of a salamander. 
Figs. 20 and 21 contain nuclei with constrictions dividing them into nearly equal portions. 
Fig. 22.— Contiguous cells, each containing a nucleus about half the size of those prevailing 
in the tissue, and, therefore, probably the result of cell-division by the direct process. 

It is believed that this mode of division does not result in the 
formation of cells that have the complete character of the parent- 
cell, and that their descendants form a degenerate race that is 
destined to extinction. It is quite obvious that no such precise 
partition of the chromatic substance is likely to take place as that 
which is characteristic of karyokinesis, and if the chromosomes are 
really the carriers of hereditary peculiarities, this mode of division 
can hardly favor their perfect transmission. 


The various parts of tlio body are composed of a small number of 
"elementary tissues." Each of these elementary tissues has a definite 
structure, but the detailsof that structure may vary within certain lim- 
its in different parts of the same mass or in different situations within 
the body. Such variations can usually be referred to differences in the 
functional activity assigned to the tissue, Avhich is not always exactly 
the same throughout the body. For example, epithelium is an ele- 
mentary tissue consisting of cells which are nearly always rich in 
cytoplasm and are separated from each other by a very small amount 
of homogeneous intercellular substance. Wherever epithelium is 
found it has these general peculiarities of structure. But the func- 
tions demanded of epithelium are of widely diverse character in 
different situations, and its structure shows a corresponding diversity 
in its details. The fact that it is made up almost exclusively of 
cells leads to the natural inference that the usefulness of epithelium 
depends upon cellular activities. Inasmuch as these may be of 
verv different character, we should expect the tissue to vary chiefly 
in the structure and arrangement of its component cells according 
to the particular activity M'hich was needed and the manner in 
which it was utilized. Such, as a matter of fact, is the case. These 
considerations will be made clearer if we follow a little more closely 
the example offered by epithelium. 

In some situations epithelium serves to protect the underlying 
tissues from injury. But the usual injurious influences which 
threaten the tissues differ in different parts of the body, and 
must, therefore, be averted by different means. Upon the sur- 
face of the skin they are chiefly of a mechanical or chemical 
nature, and to resist them the cells of the epithelium forming the 
epidermis undergo a modification in structure, resulting in the 
formation of a superficial horny layer which is highly resistant to 
abrasion and chemical change. Upon the inner surfaces of the 



respiratory passages the conditions are different. Here the tissues 
require protection from particles of dust that may be inhaled. For 
this purpose the epithelial cells lining those passages are provided 
with minute, hair-like processes, "cilia," which execute lashing move- 
ments toward the outlets of the passages and occasion the transpor- 
tation of substances coming into contact with them toward the 
outer world. In the digestive tract the conditions are again differ- 
ent. The tissues underlying the epithelial lining need protec- 
tion from the chemical action of the fluids in the stomach and intes- 
tine, as well as from friction with their solid contents. The cells 
of the epithelium meet these needs by a secretion of mucus, which 
is discharged upon the inner surfaces of the digestive organs, where 
it serves as a protective layer and as a lubricant. 

In other situations epithelium has an excretory function, which is 
less clearly of value in protecting its immediate surroundings, but 
is essential for the protection of the whole organism from substances 
"which would exert an injurious effect if they were permitted to ac- 
cumulate in the circulating fluids of the body. These substances 
are absorbed from those fluids by epithelial cells, from which they 
are discharged from the body either unchanged or after transforma- 
tion into other chemical compounds. Here the most obvious prod- 
ucts of cellular activity are of no use in the economy, and are elim- 
inated from it; but it is not improbable that the cells which separate 
them or their antecedents from the circulating fluids may also 
discharge useful substances into those fluids (" internal secretion "). 
We must not assume that the most obvious function exercised by a 
tissue is the only service it does to the organism. 

The epithelium which carries on this eliminative function is nearly 
always associated with other elementary tissues to form an organ, 
called a "gland," in which the epithelium is the functionally active 
tissue, the other tissues being subservient to it. The glands of the 
body difler considerably in both structure and function, but in all 
of them it is epithelium which elaborates the materials essential to 
the formation of their normal secretions. Mention has already 
been made of those glands which furnish secretions charged with 
waste materials to be eliminated from the body. Such glands are 
called excretory glands, and are exemplified by the kidney. Other 
glands, distinguished as secretory in a restricted sense, furnish secre- 
tions which are of service to the organism. Examples of such 
glands are those which discharge their secretions into the alimentary 


tract where, by virtue of the ferments tliey contain, they prepare 
the food for absorption. Another example of a secretory gland is 
furnished by fhe sebaceous glands of the skin, which produce an 
oily substance serving to keep the e[)idermis upon which it is 
discharged soft and pliable. 

In the secretory glands the cells of the functional epithelium 
elaborate within their bodies the substances necessary to give the 
glandular secretion its peculiar and useful characters. These sub- 
stances accumulate within the cells, where they are stored until 
required, when they are discharged into the secretion. While in 
the stored condition Avithin the cells these substances may have a 
different chemical constitution from that which they acquire when 
they are discharged from the cells. A simple example of this 
chemical transformation is furnished by the liver, in the epithelial 
cells of which carbohydrates are stored as glycogen, to be liberated 
as a closely related chemical substance, glucose. In like manner 
the ferments stored in the epithelial cells of the digestive glands 
are not fully formed while in that situation, but exist in states 
known as " zymogens," from which the potent ferment appears to 
be readily formed when the cells are called upon to furnish it. 

It is apparent, then, that the elementary tissue, epithelium, can- 
not have the same microscopical structure in all the situations in 
which it is found ; but, notwithstanding these variations, wherever 
epithelium occurs it presents certain general structural peculiarities 
Avhich are constant and which distinguish it from the other element- 
ary tissues. Similarly, each of the other elementary tissues pre- 
sents variations in the details of its structure in different situations, 
but always retains certain general structural characteristics dis- 
tinguishing it from all the other elementary tissues. It is the first 
task of the student of histology to learn to recognize and identify 
these elementary tissues wherever they occur and however they may 
vary from the type which is first presented to him for study. 

In the follow'ing chapters an attempt is made to give the student 
an idea of the essential structure of the elementary tissues, so that 
he may recognize them in specimens which he examines with the 
microscope. For this purpose they have been arranged in the 
order of their structural simplicity. 

When examining a specimen under the microscope with a view 
to recognizing the elementary tissues it contains, the student should 
habitually ask himself the following questions : (1) What are the 


general characters of the cells entering into the structure of the 
tissue? (2) What kind of intercellular substances separates those 
cells ? (3) How are the cells arranged with reference to each other 
and the intercellular substances? Correct answers to these three 
questions will enable him to quickly determine the nature of the 
tissue he is observing, even if it should vary considerably in struct- 
ural details from examples of the same tissue with which he has 
already become familiar. 



General Characters. — (1) The cells possess thin membranous bodies, 
except at the site of the nncleus, to enclose which the cell-body is 
thickened. (2) The intercellular substance is minimal in amount; 
clear and homogeneous in character. (3) The cells are arranged, 
edge to edge, in a single layer. The wavy or denticulate edges of 
neighboring cells fit into each other, being separated by a mere line 
of the intercellular substance which in this tissue has received the 
name of " cement-substance " (Fig. 23). 

Endothelium forms a thin membranous tissue composed almost 
exclusively of cells. It occurs in its most isolated form in the cap- 
illary bloodvessels, the walls of which are simply tubes of endo- 
thelium, supported externally by the surrounding tissues and fluids 
and internally by the enclosed blood. It also covers the tissues 
surrounding the serous cavities of the body, where it serves both as 
a lining to the cavities and a smooth covering to the organs, dimin- 
ishing the friction resulting from their movements against each 
other. It does not occur in any situation where it would be exposed 
directly to the external world. 

The cells of endothelium vary somewhat in size and sha])e. They 
may be polygonal, diamond, or stellate in form, and during life are 
soft and extensible so that their sizes may be modified by stretching 
or tension in one or more directions. The cell-bodies, or cyto])lasm, 
are usually clear and apparently structureless or only slightly granu- 
lar, but occasionally some of the cells are smaller and more granular 
than the majority. This is especially marked in the cells surround- 
ing minute apertures that are found here and there in the endo- 

' The term " epithelial" is used here in its most inclusive sense to designate 
thnse tissues whicli cover surfaces, whether tliose surfaces are exposed to the outer 
world, as, for example, the skin and the mucous membranes, or are wholly enclosed, 
as are the inner surfaces of tlie bloodvessels, lymphatics, and serous surfaces. 



thclial lining; of the serous cavities (Fig. 24). These openings are 
called stomata and furnish a direct communication between the se- 
rous cavities and the lymphatic spaces in the tissues surrounding 
them. These openings virtually convert the serous cavities into 
enormous lymph-spaces forming a part of the general lymphatic 

Fig. 23. 

Mesentery of frog treated with silver nitrate. The mesentery is covered on both surfaces 
with a layer of endothelium. Between these is areolar connective tissue containing 
bloodvessels, lymphatics, and nerves. In this figure only the two endothelial layers and 
a capillary bloodvessel are represented: o, nucleus of endothelial cell belonging to upper- 
most layer; b, nucleus of cell belonging to deep layer forming the lower surface of the 
specimen; c, intercellular cement between cells of upper layer of endothelium ; d, d, 
nuclei f)f endothelial cells, forming a capillary bloodvessel, seen in profile. The bodies of 
these cells are not reproduced in the figure. The cement in the deep layer of endothe- 
lium is represented by finer linos to distinguish it from that belonging to the upper layer. 

The edges of contiguous endothelial cells are not everywhere in 
equally approximation to each other (Fig. 25). The occasional 
points whore they are more widely separated than usual are occu- 
pied either by an increased amount of the cement-substance, or pro- 
cesses from cells in the underlying tissues are here intercalated 
between the endothelial cells, reaching the surface of the serous 
membrane. In cither case th(!S(; points of separation of the endo- 
thcliiil cells are not o])enings through the tissue, though, as we shall 
see in a subsequent chapter, they are spots where the tissue is rela- 



tively more ])crvioiis tlian clsowhcro. Thoy arc callod pseudostomata, 
to distingLiii^h them from the stomata already mentioned. 
-« ViQ. 24. 

Endothelium on a serous surface of the frog. (Klein.) a, stoma bounded by endothelial cells 
with granular cytoplasm; 6, pseudostoma. The nuclei of the cells are not represented. 

The intercellular substance in endothelium is so small in amount 
and so homogeneous and transparent that it escapes observation 

Fig. 25. 

1- '^ 

Enilotlu-Iial lining: of a small vein treated with silver nitrate ; dn<:. (Enselmann.) The lif?- 
ure rei)resents a tube formed of endothelium the cells of which vary in size and thape. 
The whole wall of a capillary has essentially the same structure as this venous lining 
but its calibre is smaller. The upper branch in this figure may represent a capillary 
opening into the vein, a, a, pseudostomata occupied by cement-substance. 

under the microscope unless special means are employed for its dem- 
onstration. The simplest of these consists in treating the fresh 



tissue with a 1 per cent, solution of nitrate of silver for a few mo- 
ments, washing with distilled water, and then exposing it to the 
rays of the sun. During this treatment the intercellular substance 
enters into combination with the silver. Upon exposure to strong 
light this compound is destroyed, leaving an insoluble black precipi- 
tate of silver oxide. When the specimen is examined under the 
microscope, the site of the cement-substance is marked by the 
presence of this precipitate. Endothelium so treated shows a net- 
work of fine dark lines, the meshes of which are occupied by the 
cells of the tissue. When no such method has been employed to 
render the intercellular substance conspicuous, the outlines of the 
cells cannot be distinguished, and the tissue appears as a continuous, 
nearly homogeneous membrane containing nuclei at more or less 
regular intervals. When seen in profile or vertical section, endo- 
thelium appears as a delicate line, expanded at intervals to enclose a 
nucleus (Fig. 26). The nuclei of the endothelial cells are round or 

Fig. 26. 

Diagram of vertical section through a serous membrane : a, nucleus of endothelial cell : b^ 
body of cell; c, line of junction between two cells occupied by cement-substance ; d, pro- 
cess of connective-tissue cell occupying a portion of the intercellular space between two 
endothelial cells, one variety of pseudostoma; e, areolar tissue with fusiform and stel- 
late cells. The vessels and nerves in the areolar tissue have been omitted. 

oval, and each cell usually possesses but a single nucleus situated 
near its centre, but occasionally cells with two nuclei are observed. 
Functionally, endothelium appears to play only a passive role in 
most situations in which it is found. It furni.shes a smooth cover- 
ing for internal surfaces of the body which are exposed to 
friction, as, for example, in the serous cavities and the inner sur- 
faces of the vascular systems. In the capillary bloodvessels and 
lymphatics endothelium forms the entire wall of the vessels, and 
its thinness permits th(> passage of Huids through those walls. The 
fact that the lymj)h in dilfcrent parts of the l)ody varies somewhat. 


in composition lias led to the inference that the endothelium of the 
capilUiry walls exercises an active function in determining what 
shall pass thron<ili it; that the lymph is a sort of endothelial secre- 
tion. It is drflicult, however, to reconcile this view with the fact 
that the endothelial cells are so poor in cytoplasm. 
Endothelium is developed from the mesoderm. 


General Characters. — (1) The cells are nearly always large and 
rich in granular cytoplasm. They contain distinct round or oval, 
vesicular nuclei, of which there is usually only one in each cell. 
(2) The intercellular substance is very small in amount and is clear 
and homoo-encons. (3) The arrangement of the cells and their size 
and shape all vary greatly, giving rise to a number of varieties of 
epithelium, which are classified according to the slmpe and arrange- 
ment of the cells. In pavement-epithelium the cells are thin and 
arranged in a single layer, not unlike endothelium. In cubical 
epithelium the cells are thicker and also usually arranged in but a 
single layer. In columnar epitheliiuu the cells are })rismatic in form 
and rest with their bases u})on the surface of the tissues beneath. 
They are usually separated at their bases by pyramidal cells, so 
that the layer of epithelium cannot be said to consist strictly of but 
one layer of cells, and in some situations there are several distinct 
layers. In stratified epithelium the cells are superimposed upon 
each other to form a layer of cells, the thickness of which is several 
times the diameter of a single cell. The cells of the variety of epi- 
theliiuu called ciliated epithelium differ from those of the other 
varieties in jiossessing delicate, hair-like processes which project 
from the free surface of the tissue. 

Epithelium resembles endothelium in being com])osed almost 
exclusively of cells separated by a minimal amount of intercellular 
substance. Like endothelium, it is nearly always found covering 
other tissues and having one free surface. The two tissues differ 
greatly in the character of their cells, with one notable exception. 
This exception is found in the epithelial lining of the pulmonary 
alveoli, where the pavement-epithelium contains cells that closely 
resemble those of endothelium. These cells are, however, directly 
exposed to the inspired air, while endothelium is only found in situa- 
tions where it is i)rotccte(l from all contact with the external world. 

1. Cubical Epithelium. — The cells of this variety of epithelium 




are approximately of the same diameter in all directions. They 
may be almost strictly cnbical or spherical, but are usually polyhed- 
ral as the result of mutual compression, their contiguous surfaces 
being flattened. They are usually disposed in a single layer upon 
a surface furnished by the underlying tissues, as, for example, in 
tubular or racemose glands, but they may be aggregated to form a 
solid mass of cells filling a sac, as in the sebaceous glands of the 
skin, or in strands or columns, variously disposed, as in the liver 
and suprarenal bodies. 

It is this form of epithelium that is chiefly concerned in perform- 
ing the functions of secretion, and, for this reason, it is frequently 
designated as "glandular epithelium." 

The appearance of the individual cells varies considerably accord- 
ing to the functions that they perform and the stage of functional 
activity which obtained at the time cellular changes were arrested 
when the particular specimen was prepared for study. It will suf- 
fice for present purposes of description to call attention to the fact 
that the cytoplasm is usually highly granular, partly because of its 
own structure, partly because many of the substances elabo- 
rated and stored within the cells as the result of their functions 
appear in the form of granules (metaplasm). The nature of these 
granules varies. They may be albuminoid, zymogenic granules, or 
minute drops of fatty substances, which may coalesce to form dis- 
tinct oily globules, or they may consist of carbohydrates, e. g., gly- 
cogen. The granular condition of the cytoplasm may be so marked 

Fia. 27. 

Fig. 28. 

Fm. 29. 


Cubical epithelium. 

Fig. 27.— Six cells from the sublingual gland of a man who was executed. (Schiofrcrflceker.) 
Fig. 28.— Three isolated cells from the gastric tubules of the dog and eat. (Trinklcr.) 
Fig. 29.— Cell with highly granular cytoplasm, the result of stored metaplasm, chiefly gly- 
cogen. (Barfurth.) 

as to render tiie detection of tiie nucleus difficult in unstained speci- 
mens (Figs. 27, 28, and 29). 

In this form of epithelium the presence of two nuclei in a single 
cell is more frequent than in tiie other varieties. 


2. Pavement-epithelium. — This variety of epithelium consists of 
thin cells arranged edge to edge to form a single layer. With the 
exception of certain regions on the surfaces of the pulmonary 
alveoli, the ceHs are more cytoj)lasmic and granular than are those 
of endothelium which this tissue in other respects closely resembles. 
During fietal life the smaller air-])assages and alveoli of the lung 
are lined by a pavement-epithelium, the cells of which are nearly 
as thick as those of some varieties of cubical epithelium. When, 
lu»\v('ver, the lung is expanded by the respiratory acts following 
birth, many of the cells lining the alveoli become greatly extended 
and flattened until their boflies are thin and membranous and their 
nuclei inconsj)icuous or even destroyed (Fig. 30). These greatly 
flattened epithelial cells are found covering those portions of the 

Fig. 30. 

ravement-epithelium. Surface view ot the lining of a pulmonary alveolus ; man. (KoUiker.) 
(I, membranous cell without a nucleus; 6, nucleated granular cell ; r, cut surface of the 
vertical wall of the alveolus, the structure of which is not represented. 

alveolar walls in which the capillary bloodvessels are situated and 
permit a ready interchange of gases between the air in the alveolar 
cavities and the blood circulating in their walls. Many of the 
epithelial cells covering the tissues in the meshes between the 
capillaries retain the cytoplasmic and granular character posses.sed 
before birth and appear capable of multiplying and, perhaps, 
replacing such of the thinner cells as may be thrown otf t)r 

It will be evident, from the foregoing descriptions, that there 



is no sharp structural line separating cubical from pavement-epithe- 
lium. Functionally, pavement-epithelium is a much less active 
tissue than the cubical variety. 

3. Columnar Epithelium (Figs. 31, 32, 33).— The cells of this 

Fig. 81. 

Columnar epithelium. From tongue of pseudopus. (Seller.) a, three cells with intact cyto- 
plasm, except the central one, which contains a vacuole ; 6, three cells of which the dis- 
tal ends contain drops of fluid (vacuoles) or of metaplasm. 

form of epithelium are of a general columnar or prismatic shape 
and possess a single nucleus and a cytoplasm that is usually dis- 
tinctly granular. They are arranged with their long axes parallel 
to each other, so that their free ends form the surface of the epithe- 

FiG. 32. 

Fig. 33. 

Columnar opitlielium. 
Fig. 32.— From small intestine of the mouse. (Paneth.) a, pyramidal reserve cell, nucleus not 

included in section ; h, "gfjblet" cell, enclosing a large drop of secretion. 
Fig. 33. — From small intestine of the mouse. (Paneth.) Columnar epithelial cells seen from 

above: h, goblet-cell, tlie mucous contents darkened by the hardening process; s, s, highly 

granular cells which have recently dischargei! their secretiDU. 

liuin, while their deeper ends either rest upon the tissues beneath 
the epithelium or njxm other epithelial cells of diflercMit shape 
which form one or more layers between tlic coliiiimar cells and the 
underlying tissues. Wlicn they rest directly upon the tissues 
beneath there arc usually other epithelial cells of a pyramidal or 
oval shape which may be regarded as immature cells ready to take 
the place of such fully developed cells as may become detached or 
destroyed. The ])re.<eiice of these cells occasions a narrowing of 



the deep ends of tlic coliininar cells, so that they are not strictly 
prismatic in form. In cross-section, or when viewed in a direction 
parallel to their long axes, the cells have a polygonal form due to 
the lateral pj'cssure they exert upon each other (Fig. 33). 

The nuclei of the columnar cells are oval, situated nearer the 
base of the cell than its superficial end with their long axes parallel 
to those of the cells themselves, and are vesicular in structure with 
a distinctly reticular arrangement of the chromatin filaments. 

Columnar epithelium is found chiefly upon the free surfaces of 
mucous mend)ranes, but also occurs in some of the secreting glands. 
The minute structure of the cells varies somewhat in different situ- 
ations, but the consideration of these minutise must be deferred 
until a description of the structure of the different organs is under- 
taken in a subsequent chapter. 

4. Ciliated Epithelium (Figs. 34, 35, 36). — Ciliated epithelium 

Fig. 34. 

Fin. 8o. 

Fig. 36. 

Ciliated epithelium. (Frenzel.) 

Fig. 34.— Cubical cells with long cilia [hb). The nuclei of the cells are obscured by the gran- 
ular cytoplasm. 

Fig. 35.— Columnar cells. The redded margin, /s, corresponds to the cuticle in Fig. 37. 

Fig. 36.— Diagram illustrating variations in the structure of the ciliated ends of cells. The 
rodded portion, ok to uk, corresponds to the cuticle of other varieties of epithelium, 
though the latter do not possess the knobbed ends of the rods represented in this figure ; 
hh, cilia. 

is merely a variety of either columnar or cubical ei)ithelium in 
which the free ends of the cells are beset with delicate hair-like 
processes, which execute lashing movements in some one direction. 
It is found lining the trachea and bronchi, the cilia here serving to 
propel toward the larynx such particles of dust as are brought into 
the respiratory passages by the currents of air during respiration. 
Ciliated epithelium also occurs on the lining membranes of the nose 


and the adjoining bony cavities, the mucous membrane of the uterus 
and the Fallopian tubes, the vasa efferentia of the testis and a part 
of the epididymus, the ventricles of the brain (except the fifth), the 
central canal of the spinal cord, and the ducts of some glands. 

The possession of cilia, which are very motile organs, presents 
a marked departure in specialization from the usual metabolic func- 
tions of epithelium. Ciliated epithelium rarely exercises a secretory 
function, its stock of energy being utilized to produce motion instead 
of chemical change. But there are secreting varieties of epithelium 
possessing a " cuticle " Avhich appears to be morphologically anal- 
ogous to the cilia, but in which the fibrils are less highly developed, 
probably not motile, and, therefore, functionally not the equiva- 

FiG. 37. 

Cuticularized epithelium, intestine of dog. (Paneth.) Rodded cuticle of the free ends of 
columnar cells. In most specimens of ciliated epithelium from human tissues, where no 
special care has been taken to preserve the cilia, the ciliated border presents the appear- 
ances shown in Fig. 37. 

lents of cilia. This cuticle is highly developed in the cells cover- 
ing the mucous membrane of the intestine (Fig. 37). 

5. Stratified Epithelium. — In the varieties of epithelium hitherto 
considered the cells are, in the main, disposed upon some surface 
in a single layer, some, at least, of the cells usually extending from 
the bottom of the layer to its surface. 

Stratified epithelium is distinguished from these by being of 
greater depth and consisting of several layers of cells. The epithe- 
lium lining the cheek or the oesophagus may be taken as a typical 
example of this variety. 

The most deeply situated cells are small and nearly filled by the 
round or oval nucleus. They undergo frequent division, and as 
they multiply some of them are crowded toward the surface. For 
a time these increase in size through a growth of their cytoplasm. 
But as they are pushed nearer to the surface and farther from the 
sources of nutrition in the vascular tissues underlying the epithe- 
lium, they become flattened and their bodies lose their cytoplasmic 
character, being converted into a dry, horny substance, keratin. 


Upon the tree surtiice they are redueed to thin scales, closely 
adhering to each other and their snbjacent neighbors, but entirely 
devoid of both eytoplasni and nucleus (Fig. 38). 

Stratitied^epithelium is found upon surfaces exposed to friction, 
which it serves to protect against mechanical injury, and, in some 

Fig. 38. 

Stratified epithelium, cesophagus of the rabbit: o, karyokinetic figure in a cell of the deep 
laj-er, demonstrating the fact that the cells multiply in this region ; b, larger flattened 
cell nearer the surface ; c, horny layer made up of cells that have undergone keratoid 
degeneration ; d, underlying fibrous tissue. In one place, near the centre of the figure, 
six blood-corpuscles reveal the presence of a small vessel; e, tangential section of a small 
fibrous papilla extending into the epithelium and surrounded by young epithelial cells. 

cases, against desiccation. It forms the epidermis of the skin, 
and lines the mouth, oesophagus, rectum, and vagina. In these situ- 
ations the scaly or squamous cells of the surflice are constantly 
being removed by the attrition to which they are exposed, but are 
as constantly replaced by fresh cells from the deeper layers of the 
epithelium. Pressure and moderate friction stimulate the multi- 
plication of the cells in the deepest layers of the tissue, so that 
parts, e. c/. of the skin which are especially subjected to such influ- 
ences acquire a thicker epidermis (callus). 

AVhere the stratified epithelium consists of many layers of cells, 
as is the case, for instance, upon the skin, there is a provision for 
the nourishment of the growing cells which are somewhat removed 
from the vascularized subjacent tissues. The cells of the deeper 
layers are somewhat separated from each other, leaving a space 
between them through which nutrient fluids can circulate. Across 
this space numerous minute projections or "prickles," springing 
from neighboring cells, join each other, forming connecting bridges 
between the cells. When isolated, such cells appear covered with 
these small spicules (" prickle-cells "), and their presence probably 


increases the tenacity M'ith which the cell-remains adhere to each 
other when they become hardened and toughened on the surface of 
the epithelial layer (Fig. 39). 

These delicate bridges connecting neighboring cells are not pecu- 
liar to stratified epithelium, though they are more conspicuous in 
that tissue than elsewhere. They have been observed between the 
cells of the columnar epithelium of the intestinal mucous mem- 
brane, and also between the cells of other elementary tissues ; e. g., 
smooth muscular tissue. 

6. Transitional Epithelium (Figs. 40 and 41). — This variety re- 
sembles stratified epithelium in forming layers several cells in thick- 

FiG. 39. 


I f] ^ 

Prickle cells from human stratified epithelium. (Rabl.) Four cells with delicate processes unit- 
ing across an intervening space are represented. The lower right-hand cell is just below 
the upper surface of the section, so that its surface is seen. This is covered with minute 
spots, which are end views of the prickles directed toward the observer. The nucleus 
of this cell is not in sharp focus, a fact indicated by the fainter outline in the figure. 

ness, but differs in the character of its superficial cells. These do not 
undergo the horny change peculiar to stratified epithelium, but con- 
tinue to increase in size, forming a covering of very large cells lying 
upon those beneath. Under these largest superficial cells are pyri- 
form cells lying with their larger, rounded ends next to the topmost 
layer, while their deeper and more attenuated ends lie between the 
oval or round cells that form the one or two deepest layers of the 
epithelium and rest upon the underlying tissues. 

Transitional epithelium is found lining the renal pelves, ureters, 
and bladder. Its structure permits of a considerable stretching of 
the tissues beneath without rupture of the epithelial layer over 
them, the cells of which become flattened to cover the increased 
surface, to return to their first condition when the viscus which they 
Jine is emptied. This is notably the case in the bladder, the epi- 



tliL'lial lining of Avhich may be taken as a type of this variety of 

The functional activities of epithelium are in marked contrast to 
tlic companiiively inert character of endothelium. The cytoplasmic 

Fk;. -10. 



Transitional epithelium from bladder of the mouse. (Dogiel.) 1, S, S, and i indicate the layers 
of cells, not everywhere equally well defined, a, hyaloplasmic surface, and, 6, cyto- 
plasmic body of large superficial cell ; c, leucocyte—/, e., white blood-corpuscle that has 
wandered into the epithelium by virtue of its amreboid movements ; d, karyokinetic 
figure in a cell belonging to the deepest layer. Beneath this layer is the fibrous tissue, 
which is covered by the epithelium and forms a part of the wall of the bladder. The 
superficial cell, which is fully represented, contains two nuclei, a not verj- infrequent 
occurrence in these cells. 

nature of the epithelial cell, when contrasted with the poverty in 
cytoplasm of the cell in endothelium, would lead us to expect this 
diifercnce in the cellular activities of the two tissues. At the begin- 
ning of this chapter a sketch of the manifold functions of epithe- 

FiG. 41. 

Transitional epithelium. Isolated cells from the bladder of the frog. (List.) 

lium was s^iven. It is a fair jjeneral statement of its usefulness to 
say that epithelium is chiefly concerned in bringing about chemical 
changes in substances brought to it. Sometimes these substances 
are elaborated into fresh cell-constituents, and the activity of the 


tissue is displayed chiefly in an active multiplication and growth of 
its cells. This is especially true in the stratified variety, where pro- 
tection is provided by a constantly renewed supply of cells. In 
other cases the substances received by the cells are elaborated into 
definite compounds destined to form the essential constituents of a 
secretion. This secretory function of epithelium is an extremely 
important one, and for its performance that tissue is usually ar- 
ranged in a special structure or organ, called a' gland. A brief state- 
ment of the general characters and classification of these organs 
may here appropriately find a place. 

Secreting Glands. — The simplest type of secreting structure con- 
sists of a surface covered with a layer of epithelium, the cells of which 
are endowed with the power of elaborating a secretion and discharg- 
ing it upon their free surfaces (Fig. 32, 6). The tissues supporting 
the epithelium belong to the connective tissues, and are fibrous in 
character and well provided with bloodvessels, lymphatics, and 
nerves. These bring to the epithelium the substances necessary for 
its nourishment and work, and place its activities under the control 
of the nervous system. Between the epithelium and the fibrous 
tissue supporting it there is frequently a thin membranous layer of 
tissue that often appears quite homogeneous, evidently belongs to the 
connective tissues, and has received the name of "basement-mem- 
brane." This appears to oifer a smooth surface for the attachment 
of the epithelial cells, which receive their nourishing fluids through it. 

The epithelial surfaces of many of the mucous membranes are 
examples of the foregoing simple secreting structure. The secretory 
function is here of use as an adjunct to the protective function 
assigned to the epithelial covering, and the quantity of secretion is 
but slight under normal conditions. Where the volume of secre- 
tion required is considerable some provision for an increase in the 
extent of secreting surface is necessary. This may be accomplished 
by an invagination of that surface, which then forms the lining of 
one or more tubes or sacs, into which the secretion furnished by the 
epithelial cells is discharged. Such an arrangement of the tissues 
constitutes a gland, and it is evident that tliese may be arranged 
into groups or classes according to whether the secreting surface 
forms a single tube or sac, or several such tubes or sacs, uniting to 
form a single gland. Thus, there may 1m; simple or compound tubular 
glands, or simple or compound saccular glands. Whether the deeper 
portions of the gland have a tubular or saccular structure, the secre- 



tion of the glaiul is discharged upon some free siirfiice through a 
tubular outlet, called the duct. This is frequently lined with a nou- 
socrt'ting layer of epithelial cells differing in character from the 
actively secreting epithelium in the deeper portions of the glandular 
passages (Figs. 42-47). 

Fig. 42. 

Fig. 4.3. 

■5- ^ 

Fig. 44. 

Fig. 4-5. 

Diiifjrams representing various types of gland. 

Fig. 42.— Simple tubular gland : a, epithelium covering the surface on which the secretion is 
discharged; b, mouth of gland; c, epithelium lining the duct. Thi.s gradually passes 
into the secreting epithelium. Some simple tubular glands have no such distinction 
between the cells near the mouth and those nearer the fundus, but all the cells are of the 
secreting variety— /.f., e.\ercise that function, f. secreti>ry 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. 


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 



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 


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. 


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- 

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. 




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. 

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. 



(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 




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 

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 



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 


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- 

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. 


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 

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- 


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 


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 


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 

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 

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 


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. 


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 



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 

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 



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 

Fro. 61. 


— 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 


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 



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- 



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 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 

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 



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. 


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 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 


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. 




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 



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. 


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 



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 


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 



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 (<i') will be ditlicult of detection. 
At the same time those portions of cells which lie at the top of the section will obscure 
the outlines of the cells beneath. Thus, at the point 6 the outlines of the cells /and e 
will be difficult of detection because covered by the cells k and a. and also because the 
cell i overlai)S tlu; cell e. If the plane of junction were perpendicular to the surface of 
the section, the outlines of iand e wo\ild be nuich more clearly defined. 

This brief analysis will .serve to show that the outlines of the cells will rarely be seen with 
distinctness in longitudinal sections of smooth muscular tissue. On the other hand, the 
nuelii of the cells will be prominently visible in stained sections because of the color 
fh(;y have received. For the recognition of this tissue, when so cut, we must, therefore, 
def)end chiefly upon the character and distribution of the nuclei. 

In order to avoid an unnecessarily complicated diagram, nuiuy of the cells represented in 
the upper cut have been omitted from the lower figure. 



so thin as often to escape observation. These ditterenccs render it 
easy to distinguish the two kinds of tissue in spite of their general 
similarity when seen in cross-section. 

It is, of -course, rarely that sections contain smooth muscular 

Fig. 71. 

Fjg. 72. 



a' b' c' d' 

Diagrams of smooth muscular fibres cut in various directions. 

Fig. 71.— Fibres cut exactly perpendicular to their long axes. The lines A A and B B in the 
upper figure indicate the portions of the fibres included in tlie section, winch is viewed 
from above in the lower figure. The cross-sections of the fibres a and b contain cross- 
sections of the nuclei ; those of c and d are smaller and devoid of nuclei. 

Fig. 72.— Fibres cut obliquely to their long axes. When the upper surface of the section, 
marked by the line A A in the upper figure, is in sharp focus, the sections of fibres appear 
as in a, b, c, and d of the lower figure. Wlien the bottom of the section. Indicated by the 
line B B in the upper diagram, is in clear view, the sections of the fibres appear as shown 
at a', V, c' , and d'. It will be noticed that the optical section of fibre a in the upper dia- 
gram has moved from a to a' in the lower diagram. As the focus was changed, the nucleus 
in fibre a was constantly present and its optical section appeared of uniform size. This 
could only be the case wlien the inicleus was rod-shaped and of the same diameter 
throughout that portion contained in the section. In the fibre d the nucleus was visible 
when the upper surface of the section was in focus, but disappeared when the focal plane 
•was depressed. 


Fig. 73. 

Diagrams of smooth muscular fibres cut very obliquely. The explanation of Fig. 72, already 
given, will make this one clear. In this case the outlines of the fibres in section will be 
less sharply defined than in the preceding ease, because, for instance, at the point a the 
fibre a' is cut so as to leave only a thin edge, difficult of detection, and the fibre b has had 
such a thin slice removed from it that the loss would be hardly perceptible. The appear- 
ance of the section would, therefore, be much less easy of interpretation than is repre- 
sented in the lower figure, where the outlines of the sections are equally distinct 

tissue cut exactly in either of the directions just considered. In the 
majority of sections that come under observation the muscle-fibres 
are cut obliquely, and the oval or polygonal areas which result are, 
therefore, elongated. The nuclei of the cells lie at an angle with 
the line of vision, and, in consequence, appear foreshortened. If 
now we focus the instrument so as to get a sharp image of the upper 
surface of the section, and then rapidly turn the fine adjustment so 
as to bring the lower surface into focus, we shall notice an apparent 
lateral motion of the nuclei and cell-sections. This apparent lateral 
movement, due to change of focus, is an evidence of the elongated 
shape and oblique position of the objects exhibiting it ; and a little 
reflection will convince the student that such oblique sections, when 
carefully studied, are better calculated to reveal the shapes and rela- 
tive positions of the tissue-elements than either perfect longitudinal 
or cros.s-sections. He should seek to train his powers of observa- 
tion so that he may readily interpret the instructive, though at first 
confusing, images presented by such sections (Figs. 72 and 73). 

Smooth muscular tissue is not under the direct control of the will. 
For this reason it is frequently called "involuntary muscle." It is 
also sometimes designated as non-striated or unstriped muscle, in 
contradistinction to the other two varieties of muscular tissue, the 
fibres of wliifih jjresent distinct cross-striations. 

The functional (^oiitractious of smooth muscular fibres arc slujx- 
gish, Th(! fibres are slow in responding to stimulation, contract 
leisurely, maintain the contracted condition for a long time, and 
then gradually relax. These proi)ertics render the tissue of value 



in conferring; "tone" to certain structures in which it is found, 
notably the walls of the arteries and veins. They also render it 
of service in producing the vermicular movements that are essential 
for the functional activity of such organs as the stomach and intes- 

Smooth muscular tissue has a wide distribution in the body. It 
is found in greatest bulk in the uterus, middle coats of the arteries 

Fig. 74. 

Diagrams of cardiac muscular tissue. 

^.longitudinal section: a, nucleus of muscle-cell ; 6, unmodified cytoplasm; c, contractile 
substance with longitudinal and transverse striations; d, cement-substance uniting con- 
tiguous cells ; c, areolar tissue (vessels omitted) between the muscle-fibres formed by the 
union of the individual cells ; /, small bloodvessel within the areolar tissue. If the lines 
of junction between the cells were not visible, the tissue would appear as though com- 
posed of .interlacing and anastomosing fibres, none of which could be traced for any con- 
siderable distance. Such is the usual appearance of longitudinal sections of cardiac 

B, transverse section : a, section of a cell, including the nucleus ; c, section above the nucleus 
and just below a crotch formed by the divergence of a branch; 6, section above the 
nucleus and the point where the branch 1/ is given off. 

and veins, the mu.scular coats of the stomach and intestine, and the 
wall of the bladder ; but we shall find it present in greater or less 
amount in many of the organs, the structure of which we shall 
presently have to study. 

2. Cardiac Muscular Tissue ( Fius. 74 aud 75). — Tlie heart-muscle 
is composed of cells having a general cylindrical form and contain- 
ing a single (occasionally, two) nucleus. The nucleus is vesicular, 
has a distinct reticulum of chromatin, and is usually oval. It is 
situated near the centre of the cell, and is surrounded by a small 
amount of cytoplasm, which is a little more abundant at the ends 



of the nucleus. The rest of the cell-body is composed of contractile 
substance, a modification of the cytoplasm of which the cell was 
first composed, which presents a fine longitudinal and a somewhat 
coarser transverse striation. The proper intercellular substance is 
a homogeneous cement, which lies between the ends of the cells. 
These are arranged end to end so as to form fibres, the lines of 

Ftg. 75. 

Section of human heart. The direction of the section is sucli that the muscular cells are cut 
exactly perpendicular to their long axes, a, intermuscular areolar tissue. From this, more 
delicate fibrous tissue penetrates between the muscle-fibres forming the muscular bundles, 
which are imperfectly separated from each other by the broader septa of fibrous tissue. 
b, muscle-cell cut beyond the nucleus ; c, cell cut so as to include the nucleus ; d, cell cut 
just below a branch. The index line d points to that part of the cell which passes into 
the branch. The granular character of the contractile substance when seen in cross- 
section has been omitted from the figure. At the lower edge of the figure the section 
has been torn, but a .small amount of the subpericardial areolar tissue is represented. 

junction between the cells, which are occupied by the cement-sub- 
stance, being usually invisible. The cells give off branches which 
unite with each other in such a way as to convert the heart-muscle 
into a reticulum of muscular fibres. The meshes of this reticulum 
are occupied by areolar tissue, in which the vascular and nervous 
supply of the tissue is situated. Wlicre this tissue is abundant it 
may also contain a few fat-cells. The cardiac muscle-cells are 
destitute of a cell-membrane, in which respect they differ from the 
voluntary striated muscle-fibres. 



^^'lK'Il .<ec'ii in lon^itiulimil section it is diilicult to trace a given 
muscle-fibre for any considerable distance, because the occasional 
anastomosing branches of the cells cause a blending of the neigh- 
boring Hbrt« with ea(;h other. In cross-section the cells have a 
round, oval, or polygonal shape, and vary considerably in size, 
owing to the branching. Their cut surfaces are dotted with the 
minute polygonal cross-sections of the elements of the contractile 
substance, which give the cell its appearance of longitudinal stri- 
ation. These elements are called the " sarcostyles." 

Cardiac nuis(^le occurs only in the heart. It is not luider the 
control of the will, but differs from the other involuntary nuiscles 
in the force and rapidity of its contractions, which resemble those 
of the voluntary muscles. 

3. Striated Muscular Tissue (Figs. 76-79). — The voluntary muscles 
have for their characteristic tissue-element greatly elongated, multi- 

FiG. 76. 

Fig. 77. 


jjij;;"; , ;";;•■•■■ 


striated muscular tissue. 

Fig. 76. — Portion of a muscle-fibre from a mammal. (Schiifer.) This figure represents the 
appearances of the fibre when the surface i.s in sharj> 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. 



FifJ. 78. 







i<i iiiitt Off f 4MM' 

IMi III! ('(I (I t I lll'li 

Fig. 79. 

striated muscular tissue. 

Fig. 78.— Diagrams of the structure of the contractile substance. (RoUet.) Q, sarcous elements, 
appearing dark in A, light in B; Z&xxd J, sareoplasm. The sarcoplasm also lies between 
the sarcous elements in Q, appearing as light bands in A and as dark lines in B. A is the 
appearance of the fibre when the focal plane is deep ; B, the appearance when the focal 
plane is superficial (see Fig. 76). The dots Z in A and Jin £ are optical expressions of 
differences in the refraction of the sarcoplasm and sarcous elements, and do not repre- 
sent actual structures. A complete explanation of the way in which a microscopical im- 
age may contain apparent objects which have no actual existence cannot be entered into 
here. It is due to the fact that regularly alternating structures of different powers of re- 
fraction affect rays of light verj' much as they are affected by a fine grating, producing 
diffraction spectra. These spectra may interfere with each other, occasioning an alter- 
nation of light and dark bands or areas above the specimen. AVhen the focal plane is 
changed the light areas become dark and the dark areas light, but sometimes with an 
alteration in their outline and relative sizes, as exem7)lified in the cuts. 

Fig. 79.— Cross-section of a muscle-fibre. (Rollet.) The fine reticulum, collected into larger 
masses at a few jKiints in the midst of the contractile substance, is composed of sarco- 
j)lasm. The clear areas within this reticulum are the cross-sections of the sarcous ele- 
ments. These cross-sections are sometimes called "Cohnheim's areas." Immediately 
beneath the sarcolemma are cross-sections of two nuclei. 

nucleated, cylinflrical cells. Tl)e })ody of cells is almost ex- 
clusively composed of a very complex, contractile substance which pre- 


sonts hot Iiloiit^itiidinal a n<ltransvcrsestriat ions, the latter much coarser 
and pntinint'iitthan tlic iormer. Itmust suffice iisto consider this con- 
tractile substance as made up of a number of prismatic bodies, 
" sarcous elements," which are arranged end to end to furm col- 
umns, sarcostyles, extending parallel to each other, from one end 
of the cell to the other. The sarcous elements of all the sarcostyles 
He in planes perpendicular to the long axis of the cell. It is, 
therefore, possible to separate the contractile substance into a 
number of fibre-like columns (sarcostyles, Fig. 65), made up of sar- 
cous elements attached at their ends, or to split it transversely into 
disks composed of sarcous elements lying side by side. Between 
the sarcous elements is a substance which has received the name 
" sarcoplasm." 

The contractile substance is enclosed in a thin, homogeneous mem- 
branous envelope, called the " sarcolemma." The nuclei of the cell lie 
immediately beneath the sarcolemma, between it and the contractile 
substance, and are surrounded by a small amount of unmodified 

The muscle-fibres lie parallel to each other and to the general 
direction of the muscle which they compose, and are separated by 
loose areolar tissue, containing their vascular and nervous supplies. 
When seen in cross-section they are circular or polygonal in form, 
and the cut surface of the contractile substance appears crowded 
with small polygonal areas, the sections of the sarcous elements, 
between which is the sarcoplasm. Where the nuclei are included 
in the section they appear somewhat flattened and lie at the edge 
of the contractile substance, where a thin zone of cytoplasm may 
sometimes be detected around them. The sarcolemma which lies 
outside of these constituents of the cell is so thin that it can rarely 
be distinctly seen. 

The muscle-fibres are in close contact at both ends with the dense 
fibrous tissue of the tendons attached to the muscle. 



The nervous tissues, like the muscles, are tissues of special func- 
tion, and are composed of highly specialized structures. Of these, 
only the ganglion-cells, the nerve-fibres, the neuroglia, and a few of 

Fig. 80. 

Nerve- and neuroglia-cells from pray matter of spinal cord ; ealf (Lavdovvsky.) The figure 
represents two isolated },'anf,dion-eells, with braiiehins protoplasmic processes, and each 
with a single axis-cylinder ])roecss, en. The axis-cylinder process of the lower cell gives 
olf a branch a short distance from the cell. Between the ganglion-cells are those of the 
neuroglia. The protoplasmic processes of the nerve-cells subdivide into very delicate 
fibres, which lie among those of the neuroglia-cells. 

the modes of terminal distribution of the nerves will be considered 


rrssuEs of special function. 95 

1. Ganglion- or Nerve-cells (Fi<r.s. 80 and 81). — Nerve-cell.s vary 
groatlv l)()tli in shajx' and A/x\ Tl»cy are ricli in cytoplasm, and con- 
tain an nnusnally large nucleus, generally spherical in shape, within 
the reticulunhof wliit'li there is nearly always at least one conspicu- 

Section of \inipolar nerve-cell from prray matter of spinal cord. (Flemming.) This figure 
shows the fibrillation of the axis-cylinder process and the cytoplasm of the cell, as well 
as the prominent chromophilic granules in the latter. 

ens nucleolus. The cell-bodies may be spherical, ovoid, polyhedral, 
or stellate in form, and are prolonged into one or more long pro- 
cesses. Some of these taper and branch repeatedly, the ultimate 
delicate fibrils terminating in free extremities lying in the inter- 
cellular substance, " dendritic processes." At least one of the 
processes emanating from each cell is coaiver tiuin these dendritic 
processes, and is prolonged into a nerve-fibre, forming the essen- 
tial constituent of that structure. This process is called the 
"axis-cylinder process." It does not branch as freely as the 
other processes, but may give oif one or more lateral twigs near 
its origin. 

It is customary to divide the nerve-cells into unipolar, bipolar, 
and multipolar cells, according to the number of processes proceed- 
ing from them. The unipolar cells are connected by their single 
processes with nerve-fibres, and many of tiie bipolar cells, which 
have a fusiform shape, lie in the course of a fibre with which 
the two processes are continuous. In such cases one of the 


processes is an axis-cylinder process. Tlie multipolar cells have 
one axis-cylinder process, the rest being of the dendritic type 
already mentioned, which are distinguished as '^protoplasmic" 

Xerve-cells are, as a rule, larger than the other cytoplasmic cells 
of the body, with the exception of the larger epithelial cells. Their 
cytoplasm is so finely granular that the cells look much more trans- 
parent than those of epithelium. With a high power the cytoplasm 
frequently exhibits fine striations, which are prolonged into the 
processes, giving them an appearance of longitudinal fibrillation. 
These appearances are due to the arrangement of the fibrils of 
spongioplasm. Considerable attention has of late been given to 
certain granules, which become evident in the cytoplasm when 
nerve-cells have been fixed in alcohol or in acid solutions. These 
granules have an affinity for dyes, " chroraophilic granules," and 
usuallv occur in groups in the neighborhood of the nucleus. Their 
significance is not yet understood. 

The protoplasmic processes of the nerve-cells diminish in diam- 
eter as they branch, and they also present occasional varicosities, 
which give them an irregular contour. They terminate either in 
fine-pointed extremities or in little, knobbed ends, and do not unite 
with those of neighboring cells, but form with them an intricate 
interlacement of delicate nervous twigs. 

The axis-cylinder processes arise in conical extensions of the cell, 
and then become uniform in diameter and of a smooth contour 
without varicosities. When tliey l^ranch the two divisions retain 
their size throughout their course until they enter into the forma- 
tion of some terminal structure. 

The average size of the nuclei of nerve-cells is greater than that 
of the other nuclei in the body, but they appear to contain less 
chromatin, and therefore stain less deeply and present a less distinct 
intranuclear reticulum. 

Nerve- or ganglion-cells are found in the gray matter of the 
central nervous system, in the ganglia, and sometimes in the course 
of nerves and in their peripheral terminations (Fig. 82). 

2. Nerve-fibres. — There are two varieties of nerve-fibres : the 
white, or niedulhited, and the gray, or non-mcdullated. These 
differ both in their appearance when seen by the unaided eye and 
in their micr()sco])ical structure. 

(a) Medullated nerve-fibres consist of a central cylindrical struct- 



ure running a continuous course from the cell {giving it origin to 
the peripheral termination of the nerve, called the "axis-cylin- 
der " ; an external membranous envelope, the " neurilemma " ; and 
a semisolid material, the "myelin," "white substance of Schwann," 
or " medullary sheath," lying within the neurilemma and surround- 
ing the axis-cylinder. 

The axis-cylinder is a greatly elongated process (axis-cylinder 
process) springing from a nerve-cell. It is marked by longitudinal 

YiG. 82. 

ir\^ ^^ '« 

Small ganglion in tiie tongue of a rabbit: a, a', ganglion-cells ; a', cell, with the beginning 
of its axis-cylinder process ; b, meduUated nerve-fibre in cross-section ; c, fibrous tissue 
within the ganglion (part of this fibrous structure may be composed of non-medullated 
nerve-fibres) ; d, areolar tissue surrounding the ganglion and containing adipose tissue in 
the upper and lower parts of the figure. To the left is a striated muscle-fibre. The gan- 
glion is seen in cross-section, so that its connection with the nerves, in the course of which 
it lies, is not visible. 

striations, which appear to represent exceedingly delicate fibrils 
composing the axis-cylinder. These fibrils frequently separate at 
the distal extremity of the nerve and take part in the construction 
of the various forms of nerve-endings. A more minute study of 
the axis-cylinder leads to the inference that it is composed of 
spongioplasm, continuous with that of the body of the cell, and 
that the appearance of longitudinal striation is due to the elongated 
shape of the spongioplasmic meshwork and the greater thickness 
of its longitudinal threads, the transverse threads uniting them 
being much less conspicuous. 




der; p, neurilemma, rendered 
distinct by the retraction of 
the myelin of the medullary 
sheath. In the left-hand flg- 

FiG. 83. The neurilemma, or external in- 

vestment of the nerve-fibre, called 
also the " primitive sheath," or 
" sheath of Schwann," is a thin, 
homogeneous membrane enclosing 
the medullary substance or myelin. 
At regular intervals, upon the in- 
ner surface of the neurilemma, and 
surrounded by a small amount of 
cytoplasm, are flattened, oval nu- 
clei, which appear to belong to the 
neurilemma. About midway be- 
c tweeii these nuclei the nerve-fibre 

Meduiiated nerve-fibre. (Key jg constricted, forming the " nodcs " 

andKetzius.) ^, node of Ran- ^ ' '-' _ 

vier ; B, nucleus belonging to of Ran vicr. The neurilemma ap- 

the neurilemma ; c, axis-cvlin- , , i i xi „ ,i 

pears to pass through these nodes 
without interruption, so that the 
neurilemma of one internode is 

ure the clefts of Lantermann continuous with that of the adja- 
are shown as white lines in the _ '' 

darkmyelin. These figures are cent iutemodes. At the nodcS, 
taken from specimens treated t .^ -.i • .i 

with osmic acid, which colors ^"^1 apparently within the neuri- 
the fatty constituent of the lemma, is a disk, perforated for the 

myelin a dark brown or black. . t i 

passage oi the axis-cylinder, called 
the " consti'icting band " of Ran vier. It may be that this 
band is of the nature of a cement-substance, joining the 
neurilemma of neighboring internodes ; for the latter ap- 
pear to be developed from cells, probably of mesoblastic 
origin, which surround the nerve-fibres after their for- 
mation, becoming flattened to form membranous invest- 
ments of the nerve-fibre. If this view be correct, the 
neurilemma of each internode, with its single nucleus, is 
to be regarded as a single, specialized cell, derived from 
the surrounding connective tissues, and serving to protect 
the nerve-fibre. In perfect harmony with this conception 
of its nature are the facts that the nerves within the brain 
and spinal cord are destitute of neurilemma, and that when 
a nerve-fibre branches in its course the point of division 
is always at one of the nodes of Ranvier (Fig. 83). 

The medullary sheath, or myelin, is a soft material inter- 



posed between the neurilemma and axis-cylinder. It is not a 
simple substance, but contains at least one constituent closely re- 
sembling fat or oil in its chemical nature; also a substance chemi- 
cally allied tcV the keratin of" horns and the superficial cells of the 
ei)iderniis, called neurokeratin; and a homogeneous, clear fluid. 
The way in which these constituents are combined is a matter of 
doubt, the apparent structure of the medullary sheath varying 
greatly when different modes of preparing the nerve for micro- 
scopical study have been employed. But the neurokeratin appears 
to exist as a delicate reticulum pervading the medullary substance. 
The medullary sheath appears to be interrupted at irregular inter- 
vals by oblique clefts, which surround the axis-cylinder like the 
flaring portion of a funnel. These " Lantermann's " clefts are 
occupied by a soft material, probably similar to that composing the 
constricting bands (Figs. 84 and 85). 

Fig. 84. 

Fig. 85. 



Fig. 84.— Lonsitudinal view of portion of nerve-fibre from sciatic of dog. (Seliicfrerdecker.) 

S, neurilemma; T, stained substance within the clefts of Lantermann. 
Fig. 85.— Cross-section from sciatic nerve of frog. (Bcibm and Davidoff.) A, axis-cylinder, 

showing punctate sections of the fibrillfc ; B, medullary slieath stained with osmie acid ; 

n,b, apparent duplication of the medullary sheath, due to the presence of a Lantermann 

cleft; C, areolar tissue between the fibres. 

The medullary sheath is developed after the formation of the 
axis-cylinder, and is, at first, (tontinuous along the course of the 
latter. Subsequently it becomes interrupted at the nodes of 
Ranvier by the constricting disk. It seems to be derived from 



Fig. 86. 

the axis-cylinder, and may, therefore, be regarded as a product of 
that greatly extended arm of the cytoplasm of the nerve-cell. 

The amount of medullary substance present in different nerves 
varies greatly. Sometimes it is so slight as to be hardly distin- 
guishable. In other cases its thickness considerably exceeds the 
diameter of the axis-cylinder. It is present within the spinal cord 
and brain, although not enclo.sed in neurilemma in those situations. 

At the peripheral ends of the nerves, on 
the contrary, it usually disappears before 
the neurilemma. 

The individual nerve-fibres are isolated 
only at their extremities. Throughout 
most of their course they are collected 
into bundles, forming the " nerves " of 
the body. Within these bundles the nerve- 
fibres are held together by fibrous tissue 
in the following manner : a delicate areolar 
tissue containing their vascular supply lies 
between the individual fibres. This fibrous 
tissue is called the " endoneurium." The 
nerve-fibres, thus held together, are aggre- 
gated into bundles, called "funiculi," which 
are surrounded by sheaths of still denser 
fibrous tissue, rich in lymphatic spaces, 
which are called the " perineurium." This 
perineurium on its inner surface becomes 
continuous with the endoneurium just de- 
scribed. The funiculi, enclosed by their 
perineurium, are, in turn, held together 
by an areolar sheath, which has received 
the name, "epineurium," and forms the 
outer covering of the nerve. 

The funiculi do not run a distinct course 
throughout the length of the nerve, but 
give off nerve-bundles, enclosed in peri- 
neurium, which join other funiculi ; the 
nerve-fibres themselves do not, however, 
anastomose with each other. 
(6) The gray, or non-medullated, nerve-fibres are, as their name 
implies, destitute of medullary substance. They con.sist of an axis- 



Nerve-fibres from the sympa- 
thetic system. (Key and Ret- 
zius.) All the fibres except 
that marked m are non-med- 
ullated. The fibre m has an 
incomplete medullary sheath. 
n, n, nuclei i:f the neurilemma. 
These are surrounded by a 
small amount of cytoplasm, 
which is not clearly repre- 
sented in the figure. 


cylinder, wliich at intervals aj)|)ears to be nucleated. These nu- 
clei are i)resumably constituents of a membranous investment or 
neurilemma; but the latter is difficult of demonstration because of 
its thinness aiid transparency, and its constant presence is not defi- 
nitely established {¥\fr. 86). 

Unlike the mednllated variety, the gray nerve-fibres frequently give 
off branches, which join other fibres and constitute true anastomoses. 

Non-medullated fibres are most abundant in the sympathetic 
nervous system, but occur also in the nerves derived directly from 
the brain and sj)inal cord. 

3. Neuroglia. — The nerve-cells and fibres of the central nervous 
system are surrounded and supported by a tissue which is derived 
from the epiderm, and is called the " neuroglia." It must be re- 
garded as a variety of elementary tissue having functions similar to 
the connective tissues, although its origin makes its relations to the 
epithelial tissues very close. 

Neuroglia consists of cells, the " glia-cells," which vary consider- 

Fifi. S7. 

Fig. 88. 


Glia-cells from the neuroglia of the human spinal cord. (Retzius.) 
Fig. 87. — Three cells from the anterior portion of the white matter: a, processes extending to 
the surface of the cord ; 6, cell-body ; c, long, delicate process extending far into the white 
Fig. 88.— Two cells from the deep portion of the white matter. 

ably in character, and an intercellular substance, which is for the 
most part soft and homogeneous, resembling in this respect the 
cement-substance found in epithelium, but which may, here and 
there, contain a fcAv delicate fibres, possibly derived from the pro- 
cesses of some of the cells, or possibly of mesodermic origin, and, 
in consequence, belonging to the connective tissues. 



The glia-cells possess delicate processes, which lie in the cement- 
or ground-substance and form a felt-like mass of interlacing fila- 
ments, but do not unite with each other. Two types of cell may be 
distinguished, but they are not sharply defined, because intermediate 
forms are met with. In the first type the cells have relatively large 

Fro. 89. 


Fig. 90. 

Glia-cells from the human spinal cord. (Retzius.) 
Fig. 89.— Cells from the substantia gelatinosa Eolandi of the posterior horn. The cell to the 

right has a long process beset with fine, bluish branches. 
Fig. 90.— Four cells from the gray matter. 
Figs. 87-90 are taken from specimens stained by Golgi's method, which fails to reveal the 

internal structure of the cells, but is extremely Avell adapted to show the shapes of the 

cells and their extension into fine processes. 

bodies, beset with a multitude of comparatively short, very fine, and 
frequently branching processes (Figs. 89 and 90). This type is most 
frequently met with in the gray matter. The second type of glia- 
cell is represented by cells with smaller bodies and longer and some- 
what coarser processes that branch much less freely (Figs. 87 and 88). 
They also often possess one particularly large and prominent proc- 
ess of greater length than the others. The small bodies of these 
cells serve to distinguish them from nerve-cells, with which they 
might otherwise be ea.sily confounded. This type predominates in 
the white matter. 

Aside from the processes of the glia-cells already mentioned, the 



central nervous system contains fibrous prolongat 
thelial cells of the ependyma and central canal of" 
the spinal cord (Fig. 91). Fibrous constituents are 
also derived from the areolar tissue which extends 
into the organs of the central nervous system from 
their fil)r()us investments, the pia mater, in company 
with the vascular supply. 

The (jentral nervous system, then, consists of a 
small amount of a ground-substance and a great 
number of cells, most of which possess numerous 
delicate fibrillar processes which interlace in all 
directions. Some of these cells are the function- 
ally active elements of the organs, the nerve-cells. 
Others belong to the sustentacular tissue, and are 
probably functionally passive, constituting the in- 
terstitium. Both kinds of cell are developed from 
the epiderm, and are therefore genetically closely 
related to each other. 

4. Nerve-endings. — Nerve-fibres terminate in two 
ways : first, in free ends lying among the elements 
of the tissues to which the nerve is distributed ; 
second, in terminal organs, containing not only 
nerve-filaments, but cells wdiich are associated with 
them to form a special structure. The simplest 
mode of termination consists in a separation of the 

ions of the epi- 
FiG. 91. 

Ependyma and glia- 
eells from the spi- 
nal cord. (Retzius.) 
a, ependyma in the 
wall of the central 
canal ; b, nuuroglia- 
cell near the ante- 
rior fissure of the 

minute fibrillse 

Termination of nerves by free ends. (Retzius.) Xerve-endings among the ciliated columnar 
epithelium on the frog's tongue. Two gohlet-cells, the whole bodies of which are colored 
black, are represented. The other cells are merely indicated. 

composing the axis-cylinders of the medullated fibres, or the chief 
bulk of the non-medullated fibres, into a number of delicate fila- 



Fro. 9?>. 

Fia. 94. 

Termination of nerves by free ends. (Retzius.) 
Fig. 93.— Two nerves terminating in the stratified epithelium covering the vocal cords of the 

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 



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 

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. 


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 



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 

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. 


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- 



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 

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 


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 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 



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. 


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 

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. 


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- 


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 

-■ - ... ^' 


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 



of fibrous tissue at .the hilus and, through it, with the capsule at that 

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 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 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- 



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. 




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 

lum becomes continuous Avith delicate fibres given off from the 
tissues of the capsule and trabeculae (Fig. 101). The distribution 



of the lymphoid cells gives the follicles a general concentric appear- 

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. 




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 


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 



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 

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 



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. 



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 



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 


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- 

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- 

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 



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. 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 


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 


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- 
<i\iQ> 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 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. 


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 




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 



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 


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, 



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 



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. 



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 <Tsophagus with neighboring structures. A few large vessels 
entering the a-sophagus are represented in this coat. 

tion perpendicular to the surface of the basement-membrane (Fig. 

The nerves ramify in the interlobular areolar tissue and send 
delicate, non-medullatcd fibres through the basement-membrane to 
be distributed upon and between the epithelial cells. Occasionally 
small ganglia are seen upon the larger nerves. 


3. The (Esophagus (Fig. 113). — The mucous membrane of the 
oesophagus is composed of three layers. The innermost layer is 
made up of stratified epithelium. Beneath this is a layer of fibrous 
tissue, with small papillae extending into the deeper portions of the 
epithelium (see Fig. 38). Outside of this is a layer of longitudinal 
smooth muscular tissue, the "muscularis mucosae." This is but 
imperfectly represented at the upper part of the oesophagus, but at the 
lower end forms a continuous layer separating the " tunica propria " 
(Fig. 113,/) of the mucous membrane from the submucous coat, and 
becoming continuous with a similar layer of smooth muscular tissue 
in the mucous membrane of the stomach and intestine. Occasion- 
ally small, imperfectly defined lymph-follicles are met with in the 
mucous membrane. 

The submucous coat of loose areolar tissue contains small race- 
mose glands sparsely distributed through it, the ducts of which 
penetrate the mucous membrane and open u23on the internal surface 
of the oesophagus. 

The muscular coat consists of an internal circular and an external 
longitudinal layer, which at the upper end of the oesophagus are 
composed of striated muscle. This is gradually replaced by smooth 
muscular tissue further down the oesophagus, and at its lower end 
only the latter tissue is found. 

The external coat of the oesophagus is represented by a variable 
amount of areolar tissue which loosely connects it with the sur- 
rounding structures. 

4. The Stomach. — Nearly the whole thickness of the mucous 
membrane of the stomach is made up of straight tubular glands 
(gastric tubules), which lie perpendicular to the surface, and are 
separated from each other by only a small amount of a delicate, 
highly vascular areolar tissue. This is a little denser and more 
abundant below the deep ends of the glands, where it separates 
them from the muscularis mucosae forming the deepest layer of the 
mucous membrane. 

The mouths of the gastric tubules open into shallow, ])olygonal 
depressions or crypts on the surface of the mucous membrane, 
several glands opening into each depression. These depressions 
give the internal surface of the stomach a reticular appearance when 
viewed with a low power. They, and the ridges which separate 
them, are covered with a rather tall columnar epithelium. The 
glands which open into them are of two kinds: the "pyloric" 



Fm. 115. 


Fif!. 114. 

Fig. 114.— Vertical section tliroush iiincniis 
membrane of pyloric end of .stomach ; 
human. (Bohra and Davidoff.) a, co- 
lumnar epithelium covering surface of 
mucous membrane; b, crypt lined with 
somewhat lower columnar epithelium : 
c, gastric tubules; (I. tunica propria, 
somewhat lymphoiil in character ; e, nuis- 
cularis mucosre, of smooth muscular 

Fig. 11.5.— Nearly vertical section of the mucous membrane near the cardiac end of the stom- 
ach ; rabbit: a, columnar epithelium covering the surface of the mucous membrane; 
b, that lining a crypt; r, duct ; d, parietal cell extending to the lumen of the gland: 
e, lumen, readily traced for only a short distance;/, central or chief cells; {i, small 
artery, to the left and above it, a small vein ; h, muscularis mucostv, consisting of three 
thin layers of smooth muscular tissue, the niidille layer in transverse, the others in 
longitudinal section ; /, portion of submucosa. The specimen was taken from an animal 
some time after the ingestion of food, and the chief cells are, in consequence, relatively 
small in comparison with the size of the parietal cells. 



variety, so-called because more abundant at the pyloric end of the 
stomach, and the " cardiac " variety, which preponderate near the 
cardiac end. 

The pyloric glands (Fig. 114) have the simpler structure. They 
possess a comparatively deep and open mouth, lined with columnar 
epithelial cells similar to and continuous with those lining the de- 
pressions already mentioned, and, like them, mucigenous. Into 
these mouths one or more straight tubular glands, lined with low, 
granular columnar cells, discharge their secretion. 

The cardiac glands (Fig. 115) have shallower mouths than the 
pyloric glands, and the tubes that open into them contain two sorts 
of epithelial cells : 1, the " chief" or central cells, which line and 
nearly fill the whole tubule, leaving only a very small and some- 
what tortuous lumen in the centre ; and, 2, the parietal cells, lying 
at intervals between the central cells and the surrounding connective 
tissue, but sometimes projecting between two central cells nearly 
or quite to the lumen of the gland. Very fine channels run from 
that lumen to and around these parietal cells, which are believed to 
produce the free acid of the gastric juice (Figs. 116-118). 

Fig. 116. 

Fig. 117. 

Fig. 118. 

Crcss-sections of gastric glands ; dog. (Hamburger.) 
Figs IIG and 117.— From the cardiac end of the stomach, showing the chief or central cells 
and the parietal cells. 116, from a dog killed during the second hour of digestion. The 
central cells are relatively large, and the lumen is reduced to a mere line, appearing as 
a dot in the centre of the 117, from a dog killed during the seventh hour of 
digestion. The parietal cells are relatively large, and the lumen more distinct than in 
IIG, owing to loss of material on the part of the central cells and a gain on the part of the 
parietal cells. One of the latter is in communication with the lumen through a small 
channel between the central cells. 
Fig. 118.— From the pyloric end of the stomach during the fifth hour of digestion. The cells 
b have partcil with their secretion and are compressed by the cells a, which still retain 
the materials stored for secretion. The lumen of the gland is much larger than that of 
the glands at the cardiac end of the stomach. 

Besides the secreting glands, the mucous membrane of the stom- 
ach sometimes contains small lymph-follicles. Its blood- and 
lymph-supplies are abundant, and nerves are distributed to its 
various tissue-elements. 


The deepest layer of the mucous membraue is the muscularis 
mucosa?, made up of two or tlircc strata of smooth muscular tissue 
iu wliicli the fibres run in different directions. 

The subnnicous coat of the stomach consists of loose areolar tissue, 
which allows considerable freedom of motion between the mucous 
nu'ml)rane and the muscular coat. A\ hen, therefore, the organ is 
empty the contraction of the muscular coat throws the mucous 
membrane into coarse folds (rugie). The large arteries, veins, and 
lymphatics course in this submucous tissue, and thence send branches 
into both the raucous and muscular coats. The nerves also form a 
ganglionated plexus in this coat. 

The muscular coat consists of an external longitudinal layer, 
inside of which is another laver encircling the oro;an. The external 
layer is continuous with the outer muscular layer of the oesophagus. 
The internal muscular layer of the latter organ is continued into the 
wall of the stomach as a scattered set of oblique fibres lying internal 
to the encircling fibres already mentioned. The muscular coat of the 
stomach may, therefore, be considered as composed of three layers, 
the innermost of which is incomplete. At the pylorus the encircling 
muscular layer is thickened. 

Aside from the fibrous tissue that more or less completely sepa- 
rates its layers, the muscular coat contains ganglionated nerve- 

The external surface of the stomach is covered with a serous in- 
vestment of peritoneum, except along the curvatures, where the 
peritoneum is reflected from the organ, permitting the passage of 

its vessels and nerves. 

5. The Duodenum. — The structures characteristic of the small 
intestine first make their a})pearance in the duodenum. We shall 
first consider those features which are found throughout the small 
intestine, and then describe those which are peculiar to the duod- 
enum (Fig. 119). 

The mucous membrane presents thin, transverse folds, the val- 
vule conniventes, which are not obliterated when the intestinal wall 
is stretched. They are made up of a thin layer of areolar tissue, 
extendinsf from the submucous coat of the intestine, which is cov- 
ered on both surfaces with mucous membrane. This arrangement 
serves greatly to increase the surfiice of mucous membrane coming 
in contact with the contents of the intestine, a provision facilitating 
absorption of the products of digestion. 



The valvule conniventes begin a short distance below the pylorus, 
and are very numerous and prominent in the duodenum, but become 
progressively less frequent and pronounced in the lower portions of 
the small intestine. 

The absorbent surface of the small intestine is still further in- 

FiG. 119. 

Diagram representins the structure of the human small intestine. (Bohm, Davidoff, and 
Mall, slightly modified.) Two villi are represented. In the one on the left the blood- 
vessels are shown ; in the one on the right, the lymphatics. The line .S' indicates the sur- 
face of the mucous membrane between the villi, a, central lacteal vessel; h, smooth 
muscular fibres extending into the villus from the museularis mucosae : c, lymphadenoid 
tissue beneath the epithelial covering of the villus; d, crypt of Lieberkiihn ; e, tunica 
propria of lymphadenoid tissue, and continuous with that of the villus; /, museularis 
mucosse, forming the deepest portion of the mucous membrane; .7, snbmucosa containing 
the larger bloodvessels and the lymjihatic plexus h; i, encircling layer of the muscular 
coat; J, longitudinal layer; k, lynifihatie ple.xus within the muscular coat; /, serous coat; 
m, vein. The cryj^ts are lined, and the villi covered, with columnar epithelium. 

creased by the presence of innumerable minute, finger-like projec- 
tions from the surface of the mucous membrane, the villi. These 
are just discernible by the unaided eye, and give the internal surface 
of the intestine a velvety appearance. 

Till-: i)ir;i:sriVK organs. 139 

Between the attached ends of the villi, and opening upon the sur- 
face of the nuicous nicinl)rane, are tubular depressions extending 
nearly to the nuiscularis niiicosto. These are the "crypts of Liehcr- 
kiihn," and have the api)earance of simple tubular glands; but it is 
doubtful if they elaborate auy jieculiar secretion. These crypts are 
present, not only in the whole extent of the small intestine, but 
also throughout that of the colon. 

The crypts of Lieb(M"kiihn are lined with columnar epithelium, 
which also covers the surface of the mucous membrane and the villi 
springing from it. The cells composing this epithelium multiply in 
the crypts, and, as they mature, are gradually moved toward their 
orifies, whence they replace those that have been destroyed upon the 
surfaces of the villi. The cells possess a granular cytoplasm, which 
becomes infiltrated with fat during digestion ; an oval, vesicular 
nucleus ; and a delicate cell-membrane. The free ends of the cells 
are formed by a well-marked cuticle, which may be either homo- 
geneous in aj)pearauce, or present very fine vertical striations (Fig. 
37). Many of the cells are mucigenons and contain globules of mucus 
near their free ends, or appear as goblet-cells after the discharge of 
that secretion. These cells are more abundant on the villi, where 
they are older, than in the crypts lined with less mature cells. 

The epithelium rests upon a basement-membrane, which contains 
nuclei, and is therefore composed, in part at least, of cells. Beneath 
this basement-membrane is a layer of reticular and areolar tissues, 
containing a variable number of lymphoid cells and numerous 
capillary bloodvessels. The rest of the mucous membrane, down 
to the muscularis mucosa?, and the axes of the villi are occupied by 
areolar fibrous tissue. 

The thin muscularis mucosa?, which forms the deepest layer of 
the mucous membrane, is made up of two layers of smooth muscular 
tissue : an internal layer, in which the fibres run transversely to the 
axis of the intestine, and an external longitudinal layer. From the 
upper surface of this muscular layer of the mucous membrane 
muscular fibres extend into the villi, in the areolar tissue in their 
axes, and serve to shorten the villi by their contraction, so that the 
villi are moved about in the intestinal contents during the process 
of absorption. In the centre of each villus is a capillary lymphatic 
vessel arising in a blind extremity near the apex of the villus. 
These lymphatics open into a lymphatic plexus situated between the 
muscularis mucosae and the ends of the crypts of Lieberkiihn, and 



thence discharge their contents into the lymphatics in the sub- 
mncosa. The mnscuLir fibres in the villi probably aid in the pro- 
pulsion of the chyle in these lymphatics (Fig. 120). 

Fig. 120. 

/ ^r^-^- 

Axial section of villus of the dog. (Kultschitzkj .) a, epithelial covering with cuticle: &, 
goblet-cell ; c, space between tapering ends of the epithelial cells ; d, cell of the base- 
ment-membrane; c, smooth mnscnlar fibres; /, reticulum of the tunica propria (the 
lymphoid cells have been, for the most part, removed) ; g, lumen of the central lymphatic 
The bloodvessels are not represented. 

Tlie submucous coat of the intestine is composed of areolar fibrous 
tissue. Outside of this coat is the muscular coat, divisible into two 
layers, which is covered throughout the whole circumference of the 
intestine, except at the line of mesenteric attachment, with a serous 
investment of the peritoneum. 

In the duodenum the submucous coat contains compound tubular 
glands, the glands of Brunner, the ducts from which penetrate the 
muscularis mucosae and open upon the surface of the mucous mem- 
brane, between the crypts of Ijicbcrkiihn. Here and there, in the 
duodenum, are little collections of lymphadenoid tissue, occupying 
an enlarged villus and often extending through the muscularis 
mucosae into the submucous areolar tissue (Fig. 121). These 



lymph-fuUiclcs nuiy be rogurded us the result of an increase in the 
amount of reticular tissue of the villus, wliicli has replaced the 
other structures usually present. In the lower portions of the 
small intestine there are collections of these solitary follicles, 
which have received the name " Peyer's patches." 

6. The small intestine below the duodenum resembles the latter 

Fig. 121. 

^^^^I^PMi""; ^^^^te 

Section of solitary follicle from the ileum. (Cadiat.) n, space loft by the disintegration of 
the central, delicate lymphadenoid tis.sue of the follicle dnringthe preparation of the sec- 
tion ; 6, columnar epithelium of intestinal surface ; c, c, villi, partially denuded of epithe- 
lium : d, crypt; e,f, muscularis mucosae; above /, the point where the vessels enter the 
follicle. The Peyer's patches are collections of such solitary follicles, placed side by side 
and destitute of villi at their upper surfaces. 

in structure, with a few inodifications, which become progressively 
more marked as the distance from the stomach increases. 

The glands of Brunner are most abundant near the upper part 
of the duodenum, more sparsely distributed further down, and 
usually disappear entirely before the beginning of the jejunum. 

The valvular conniventes, which are most highly developed a 
little below the entrance of the gall and pancreatic ducts, also 
become lower and less frequent along the course of the intestine, 
and finally disappear about the middle of the ileum. 

The crypts of I^ieberkiihn are deepest in the upper part of the 
intestinal tract, but persist in shallower form throughout its whole 
extent, as well as along the whole length of the colon. 


The Peyer's patches are most abundant in the lower part of the 
ileum, M'liere they lie in the intestinal wall opposite the line of 
mesenteric attachment, and form oval areas with their long axes 
parallel to the axis of the intestine, 

7. The Colon. — The mucous membrane of the colon is destitute 
of villi, but contains crypts of Lieberkiihn closely arranged side by 
side and lined with columnar epithelium rich in mucigenous cells. 
The muscularis mucosae is similar to that of the small intestine, and 
gives oif occasional fibres that penetrate between the crypts. 

The submucous coat resembles that of the small intestine, and, in 
common with the mucous membrane, contains solitary lymph-fol- 
licles, most abundantly in the caecum and vermiform appendix. 

The muscular coat has its outer or longitudinal layer most highly 
developed in three bands, which are situated about equidistantly 
around the circumference of the bowel and occasion a jiouching of 
the intervening wall. 

TJie serous coat is similar to that of the small intestine, but is 
occasionally extended over small pendulous projections of the 
subserous fibrous tissue, which contain adipose tissue, appendices 

8. The rectum resembles the colon in its structure, except that the 
three muscular bands present in the latter are wanting. The mucous 
membrane as it passes into the anal canal loses its tubular glands, 
and subsequently becomes covered, not with columnar, but with 
stratified epithelium, continuous with the epidermis of the skin 
around the anus. 

9. The pancreas (Fig. 122) has a structure similar to that of the 
salivary glands, but its lobules are separated and held in place by a 
rather more considerable amount of loose areolar tissue, in which 
there are occasional groups of cells of uncertain nature, but cer- 
tainly distinct from those lining the glandular acini. They are 
called the " interalveolar cell-islets," and may, perhaps, be of the 
nature of ductless glands {q. v.). 

As the ])ancreas exercises its secretory function the granules 
within its colls move toward the lumina of the acini and successively 
disa]>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- 


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. 


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 



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 



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 

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, 


77//-; IJVKR. 


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 



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 


human liver the epithelial eells of the parenchyma form a plexus 
lying in the meshes of the ea{)illary network of the interlobular 

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. 


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 

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- 


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 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 

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 


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. 



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 




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. 



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 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 



Fig. 131. 

Diagram showing the 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 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 



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 

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). 



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- 



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. 


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 


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 



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- 

The nerves of the kidney are small and apparently not abundant. 
Their larger branches follow the courses of the arteries. 



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. 


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 

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 



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 

Tiic epithelium lining the uriniferous tubules diseharges its 
secretion into the lumen of the tubules, whence it is carried by 
the stream flowing from tlie Malj)ighian bodies. The epithelial 
cells lining the convoluted tubules and the ascending branches of 
Henle's tubes appear to be those most active in carrying on the 
elimiuative fimction of the kidney. 

2. The pelvis of the kidney and its calices are lined with trans- 
itional epithelium. It consists of only three or four layers of 
epithelial cells of different shapes. The most superficial layer is 
composed of rather large flattened cells, having ridges upon their 
lower surfaces, which fill the spaces between the tops of the next 
layer. This is made up of pear-shaped or caudate cells, the hemi- 
spherical tops of which fit into the cavities between the ridges on 
the layer above, while their slender processes penetrate between 

Fig. 140. 

Epithelial cells from the pelvis of a human kidney. (Kieder.) 

the oval or round cells that make up the deepest layers of the 
epithelial covering (Fig. 140). 

Beneath the epithelium is a coat of fibrous tissue, denser near the 
epithelium and more areolar in its deeper portions. Here it is 



interlaced with smooth muscular fibres, outside of which is the 
external coat of fibrous tissue. 

3. The ureters closely resemble in structure the pelvis of the 
kidney; but the muscular fibres have a somewhat more definite 
arrangement, being disposed in an inner imperfect coat of longi- 
tudinal and an external layer of circular fibres, outside of which 
a few supplementary longitudinal fibres are, here and there, added 
(Fig. 141). 

4. The bladder also has a lining of transitional ejtithelium (Fig. 

Fig. 141. 

Epithelial cells from the human ureter. (Rieder.) 

40), beneath which is a layer of fil:)rous tissue resembling that of 
the renal pelvis, but of greater thickness. The muscular coat, 
which comes next, is thick and composed of bundles of smooth 
muscular fibres, interlacing in various directions or disposed in 
more or less well-defined strata. External to the muscular coat 
is a fibrous coat, wiiich is covered by a reflection of the peritoneum 
for a part of its extent, and in other situations passes into the sur- 
rounding areolar tissue. 

The spear-shaped cells of the transitional epithelium of the blad- 
der have thicker processes than tliose of the pelvis or ureter ; but 
when detached and macerated in the urine it is often very difficult 
to determine from their appearance from what part of the urinary 
tract such cells were derived (Figs. 142 and 143). 



5, The urethra tliftbrs in structurt' in the two sexes. In tiie 
male the |)rt)static j)ortiou is lined with epithelium resembling that 

Fi(i. 142. 


Fig. 143. 

Epithelial cells from the raucous membrane of the human bladder. (Rieder.) 
Fig. 142.— From the urinary sediment from a case of cystitis. The cells are somewhat 

swollen after maceration in the altered urine. 
Fig. 143.— Removed from the internal surface of a normal bladder. 

of the bladder. Further forward, it gradually passes into cylin- 
drical epithelium, at first more than one layer thick ; but in the 



cavernous portion of the urethra it consists of but a single layer. 
The stratified epithelium covering the glans extends for a short 
distance from the meatus into the urethra (Fig. 144). The epithe- 

FiG. 144. 

Epithelium from the human male urethra. fRieder.) 

lial lining rests upon fibrous tissue containing a number of elastic 
fibres, and this is bounded externally by a muscular coat. In the 
prostatic portion the muscular coat consists of an inner longitudinal 
and an outer circular layer of fibres, which become less well marked 
as the of the urethra is followed, the circular coat disappear- 
ing in the bulbous portion and the longitudinal fibres becoming 
scattered toward the anterior part of the cavernous portion. The 
mucous membrane contains little tubular glands, " Littr^'s glands," 
some of which are simple, while others are compounded. In the 
collap.sed condition the urethral mucous membrane is thrown into 
one or more longitudinal folds. 

In the female the epithelial lining of the urethra is either strati- 
fied or compo.'^ed of a single layer of columnar cells. The glands 
are more sparsely distributed than in the male, except for a group 
situated near the meatus. On the other hand, the muscular coat 
is thicker and consists throughout the course of the urethra of a 
well-defined internal longitudinal and external circular layer of 

From the pelvis of the kidney to the stratified epithelium of the 


nic'utus the niui:oiis iiK'iiibriines are eajjuble of secreting mucus, which 
is much increasod in amount under tlic influence of irritating sub- 
stances, sucli as concentrated urine or the various causes of inflam- 
mation. The bh)odv'essels arc most numerous and of hirgest size 
in the areohir tissue beneath the epithelium, and are accompanied 
by tiie lymphatics. The nerves are distributed chiefly to the mus- 
cular coats, but also extend into the fibrous tissue, up to and into 
the epithelium. The cells of the latter are connected by little 
protoplasmic bridges, as in the case of the epidermis, leaving minute 
channels between the cells for the passage of nutrient fluids. 



The respiratory tract consists of the larynx, trachea, bronchi, 
and lungs. 

1. The Larynx. — The interior of the larynx is lined with ciliated 
columnar epithelium, which extends over the false vocal cords and 
about half-way up the epiglottis above, and is continuous below 
with a similar lining throughout the trachea and bronchi. This 
lining is interrupted over the true vocal cords by a covering of 
stratified epithelium, and at its upper limits passes into the stratified 
epithelium lining the buccal cavity and pharynx and covering the 
tongue. Opening upon this epithelial surface, except upon the true 
vocal cords and in the smallest bronchi, are mucous glands, varying 
in number in different situations. Some of the columnar cells upon 
the surface are also mucigenous, discharging their secretion upon 
the free surface of the mucous membrane. 

The thyroid, cricoid, and most of the arytenoid cartilages are 
composed of the hyaline variety of that tissue : the epiglottis, 
cornicula laryngis, and the apices of the arytenoids, of elastic car- 

Beneath the epithelium lining the laryngeal ventricle is a con- 
siderable layer of lymphadenoid tissue. In other situations the 
epithelium rests upon fibrous tissue. 

2. The Trachea. — The tracheal wall may be divided into four 
coats: a, the mucous membrane; h, the submucous coat; c, the 
cartilage ; <J, the fibrous coat (Fig. 145). 

a. The mucous membrane is covered with ciliated columnar epi- 
thelium resting upon a nearly homogeneous basement-membrane, 
beneath which is a layer of fibrous tissue. This may be divided 
into two portions : an outer one, next to the basement-membrane, 
which is areolar in character, with a large admixture of elastic 
fibres and lymphadenoid tissue, and an abundant supply of blood- 
vessels ; and an inner one, less highly vascularized, and composed 
chiefly of elastic fibres running a longitudinal course. 


Till-: i!i:srij!ATnny oroans. 


6. Tlie .siihimicous coat is of areolar lihroiis tissue, supporting the 
mucous glands that open into the trachea, an<l the bloodvessels, 
lymphatics, and nerves, and also little masses of adipose tissue. In 
the neighborhood of the cartilages this Hl)rous tissue becomes con- 
densed to form the perichondrium. 

c. The cartilages are composed oi' the hyaline variety of that 

Fig. 14o. 

° — C 


From a lonsituflinal section throuRh the trachea of a child. (Klein.) a, the stratified 
columnar ciliated epithelium of the internal free surface; ?), the basement-membrane; 
f . the mucosa (tunica propria) ; d, the network of longitudinal clastic fibres (the oval nuclei 
between them indicate connective-tissue corpuscles) ; e, the submucous tissue, con- 
taining mucous glands; /, large bloodvessels; ;;, fat-cells; h, hyaline cartilage of the 
tracheal rings. (Only a i)art of the tracheal wall is given in the figure.) 

tissue, and are incomplete rings, interrupted behind, where the tAvo 
ends are united by a band of smooth muscular tissue. 

(1. The fibrous coat is of areolar tissue beyond the bounds of the 
perichondrium, and serves to connect the trachea witli its sur- 

3. The Bronchi. — The main bronchi branching from the trachea 
have a structure similar to that organ, but the cartilaginous rings 
become more delicate as the tubes diminish in size. 



The smaller bronchi differ in structure from the trachea in 
possessing a muscularis raucosse, with its fibres disposed in a 
circular direction, and having irregular cartilaginous plates in their 
"vvalls, instead of C-shaped, imperfect rings. The four coats may 
be enumerated as follows : 

a. Mucous membrane, covered with ciliated columnar epithelium 
resting upon a basement-membrane, beneath which is a fibrous 
tissue containing numerous elastic fibres lying parallel to the axis 
of the bronchus. Under this are the circular fibres of the mus- 
cularis mucosae. 

6. Submucous coat, similar to that of the trachea and larger 

c. Cartilaginous coat, containing the plates of cartilage that sup- 
port the walls. 

d. Fibrous coat of areolar tissue, containing a little adipose tissue 
and passing into the areolar tissue of neighboring structures. 

As the bronchi subdivide and become smaller the coats get 
thinner, and first the cartilaginous and then the muscular coat dis- 
appears. Those air-passages which are without cartilage, but have 

Fig. 146. 


!l c 1/ a 

Portion of a cross-section of u bronchiole from the lunp of a pip. (Sclinltzc.) a, areolar 
external coat ; h, muscularis mucosa : e, subepithelial areolar tissue, containing numerous 
lonpcituflinal elastic fibres, represented here in cross-section ; d, ciliated epithelium, form- 
ing the most superficial layer of the mucous membrane ; /, walls of the neiRhboring pul- 
monary alveoli. In these walls branching and anastomosing elastic fibres are shown; 
the capillarj' plexus has been omitted. 

a muscularis mucosae, arc called '' bronchioles" (Fig. 146). The 
still smaller branches, which have lost their muscular tissue, are 
known as the "alveolar passages." In the latter the columnar 



cpitheliinii liiiiii<;- the hronchi ^ives place to a pavomont-epitliclium, 
c()nipos(!(l of" small Hattcncd (;olls disposed in a single laver. The 
elastic tissue of the rniieous menihrane is continued through all the 
divisions of the air-passages, and becomes a constituent part of the 
alveolar walls of the lung itself. 

The alveolar passages open into spaces, called the " infundibula," 
in the sides of which are the openings into the alveoli of the 
lung, the ultimate destination of the inspired air. Here and there 

Fig. 147. 

\ M<ii^:^f<fi^ :^'-f '•*/*..;^ ■'js^^v^ c-<S r 7 

Section of hine (if tlu' doj:, sbowiiiir a transverse section of a bronchiole: a, bronchiole (a 
little mucus covers tlie epithelial lining); 6, muscular layer of the mucous membrane; c, 
c, radicles of the pulmonary vein ; d. alveolar 'lassaire. just at its division to form infun- 
dibula. .\n infundibuhim extends from this passage toward the bronchiole. The wall 
of the alveolar passaire at this point is similar in structure to that of the pulmonary 
alveoli, c, alveolar passage in obliiiue section. This passage is cut at a point further 
from its opening into the infundil)ula, and has a somewhat thicker wall than d. The rest 
of the section is made up of infundibula (the larger spaces) and pulmonary alveoli. 

stray alveoli open directly into the alveolar passages (Figs. 147, 
148^ and 149). 

4. The pulmonary alveoli and the smaller air-passages are so 
arranged that there are no vacant spaces ; and neighboring alveoli, 
whether they belong to a group of infundibula springing from 
the same alveolar passages or to separate groups, are so closely 
situated that they have but one common Mall dividing their cavities 



from each other. Notwithstanding this general compactness of 
arrangement, the lungs are divided by delicate septa of fibrous 
tissue into more or less well-defined lobules, corresponding to the 
smallest bronchi or the bronchioles. 

The alveolar walls are made up of a delicate, loose areolar tissue, 
containing numerous elastic fibres and supporting the abundant 
capillary plexus in which the blood suffers the gaseous exchanges 
with the air that constitute the function of respiration (Fig, 150). 

Fig. 148. 

Section of lung of the dog: a, alveolar passage opening into an inf\inrlibulum and also into 
a solitary alveolus ; b, cross-section of an infundibulum. The dotted line indicates the 
limits of the infundibular space. Opening into it are a number of alveoli. Were the 
dotted line removed, the infundibular cross-section and the alveoli around it would form 
a stellate space in the section, c, junction of two radicles of the pulmonary vein. At 
the top of the section, to the right, is an oblique section of a Itronchiole. 

Covering the two surfaces of the alveolar wall is a layer of very 
thin cellular plates (pavement-epithelium, see Fig. 30), among 
which are scattered a few cells resembling those lining the alveolar 
])a.<.sages. This cellular investment is continuous with the lining 
of the infundibulum, which is of similar character, and thence with 
the epithelium covering the inner surface of the alveolar passage. 
It is to be regarded as a special modification of epithelium, fitting 
it for usefulness in this situation. 



The lung receives blood IVoiii two soiirees : 1, venous blood, 
tliroiigli the pulmonary ;irt( rv, wliicli is oxygenated in tiu' walls of 
the alveoli ; 2, arterial blood, tlirougli the bronehial arteries. This 
arterial blood serves tor the nonrishnient of" the tissues of the lung 
and is distributed to the bronelii, interlobidar connective tissue, 
lymph-glands, and walls of the vessels. Part of this blood returns 
through the pulmonary veins; the rest through the bronehial veins. 

Fig. 149. 




^. Wis*?" ">>^ '"'wv-^J, '•-C; -S \\.s 


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 



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. 


Because of llicii- presence the lungs retract when the chest is 

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). 


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." 




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. 



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- 



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 


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. 



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 

The following organs and structures will be considered as belong- 
ing to the general group of ductless glands : the thyroid gland, the 




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 



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 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<S). The colloid is then taken 
up by the lymphatics, through which it reaches the general circula- 
tion. Thisjsan example of internal secretion which j)resents much 
of interest. It is probable that a similar, but much less obvious, 
process takes place in some of the ordinary secreting glands of the 
body, certiiin elaborated materials being returned to the circulation 
by the cells of the gland, while others are utilized for their nourish- 
ment and for the elaboration of the more obvious secretion. 

That the secretion of the thyroid gland is of importance to the 
general organism is shown by the effects of disease or removal of 
the gland upon the general nutrition. Total extirpation of the 
thyroid, together with the parathyroids, occasions the death of an 
animal within a few days, after symptoms of grave disturbances in 
the central nervous system, among which are tetanic convulsions. 
A partial removal of the gland, or its removal without that of the 
parathyroids, causes profound disturbances of nutrition, grouped 
under the title " cachexia struraipriva." The animal becomes weak, 
drowsy, and emaciated ; the skin dry and scaly, with a loosening 
of the hairs. In young animals the growth is retarded, especially 
the development of the bones, through degenerative changes in the 
epiphysial cartilages. In these, the intercellular substance becomes 
swollen and disintegrated ; the cells atrophied or destroyed. Marked 
changes, designated as myxtedema, also appear in the su])cutaneous 
tissue, which is converted into a species of mucoid tissue, probably 
as the result of an altered metabolism within the pre-existent cells 
of the tissue. The functional activity of the kidney is modified ; 
after a while, albuminuria results. Exactly similar disturbances have 
been observed in people suffering from disease of the thyroid gland. 

The foregoing facts are cited here in order to emphasize by a 
striking example the statement previously made, that the organs of 
the body are mutually dependent upon each other. 

Experimentation and clinical study liave further shown that the 
symptoms of myx(Tedema may be moderated or perhaps entirely 
arrested by feeding with thyroid extracts, or still more markedly 
by injecting extracts from thyroid glands beneath the skin, where 
they would speedily pass into the lymphatics and thence into the 
general circulation. 


Chemical examination has revealed the presence of a substance 
called " thyroiodin " in the alveoli of the thyroid gland. This is a 
proteid containing a large amount of iodine. Its production by the 
thyroid gland may be increased by feeding with substances contain- 
ing considerable iodine or by administering iodide of potassium. 
Injections of thyroiodin serve to mitigate the effects of thyroidec- 
tomy, very much as do injections of thyroid extracts. It is by no 
means clear, however, that the thyroiodin is the only substance 
elaborated by the thyroid gland which may be of use to the tissues 

Fig. 159. 

'O, ' 

Section of the thyroid gland of a kitten two months old. (Kohn.) Showing the positions 
of the outer and inner ijarathyroid bodies and a thymus follicle: t, thyroid gland ; p, 
inner parathyroid ; p', outer paratliyroid ; th, thymus follicle ; a, portion of the section 
showing the intimate relations between the thyroid and the inner parathyroid ; b, por- 
tion demonstrating a similar intimate relation between the thyroid and the tissues of the 
thymus follicle. 

of other organs, or that the thyroid may not also remove injurious 
substances from the circulation and thus indirectly benefit other 
structures in the body.' 

' Attention is also called to the possibility that an exce.ssive or morbid thyroid 
secretion may cause symptoms of disease attributable to disturbances in the functions 
of other organs, and may also occasion distur])ances in nutrition. 


Tlu' bloodvessels of the thyroid arc; ahuiidant, and form a rich 
plexus in the areolar tissue between the alveoli. The lyniphaties 
are als<j abundant and large, fbrniin<j:; a network of rather large ves- 
sels in the same situation. '\\\v nerves aceonipany the vessels, are 
destitute of ganglia, and have been traced to the bases of the ej)i- 
thelial cells^ whence they may occasionally send minute terminal 
twigs with enlarged ends between the epithelial cells. 

2. The Parathyroids (Figs. 159, 160, 161). — These are two bodies 

Fio. 160. 


V ■ •■ o ■'' 

Section of a portion i^f tlio oxIl ;,.,;; j...i..;;,;, ; ...; ..i a k.i,^., ; ,. .. i.iwnths old. (Kohn.) Show- 
ing the columns of epithelial cells separated by a delicate, vascular areolar tissue. The 
nuclei between the columns of epithelium belong chiefly to capillary bloodvessels, m, 
m, nuclei exhibiting karyoljinetic figures. 

of identical structure, which are developed in conjunction with 
the thyroid gland ; but, while the latter progresses in its devel- 
opment until it attains the structure already described, the para- 
thyroids retain a structure similar to that of the embryonic thyroid. 
They are composed of solid columns of epithelial cells, wdiich anas- 
tomose with each other, but are elsewhere separated by a small 
amount of vascular areolar tissue. They are enclosed in a very 
thin capsule of areolar tissue, but are in very close relation to the 
neighboring tissues of the thyroid gland (Figs. 159 and 161), and 
frequently also with isolated follicles of thymus tissue. 

Different observers vary in their opinions respecting the para- 
thyroids. Some regard them as reserve thyroid tissue, remaining 
dormant while the thyroid is functionally competent, but developing 


into thyroid tissue when the gland furnishes an insufficient supply of 
secretion. Other observers deny this and regard the parathyroids 
as embryonic rudiments, nearly, if not quite, devoid of function. It 
is certain that in some cases of thyroidectomy the parathyroids 
become enlarged, and that the cachexia strumipriva is not certain to 
develop after the removal of the thyroid gland unless the paratliy- 

FiG. 161. 


K -" ■ -y. 

Sell.-' ' 'M 

y u^ 

\ ^h 

Section of the inner parathyroid of a kitten two months old. (Kohn.) Showing its close 
connection with the tissues of the thyroid gland : Sc/(, alveoli of the thyroid ; P, epithelial 
columns of the parathyroid ; A', capsule separating the two. 

roids are also removed. Histological studies of the parathyroids in 
sucli cases have, howevcT, failed to reveal a tendency on their part 
to develop into true thyroid tissue. Their relations to the thyroid, 
therefore, still remain undetermined. 

In some animals — e. g., the cat — there are four parathyroid bodies, 
two associated with each lobe of the thyroid. 

3. The Adrenal Bodies (Fig. 162). — The adrenal bodies, or supra- 
renal capsules, possess a fibrous capsule, whicli is more areolar 
externally, where it frequently merges into the perinephric fat, 



Fio. 162. 

and den.ser internally, where it is reinforced in some animals by 
smooth innseiihir tihres. From 
this eapsule septa of areolar tissne 
penetrate into the substance of the 
organ and constitute its interstitial 
tissue. The parenchyma of the 
organ consists of columns of epi- 
thelial cells, which are differently 
arranged and have a somewhat dif- 
ferent appearance in diiferent parts. 
As the result of these diti'erences the 
organ has been divided into a cor- 
tical and a medullary portion. 

In the cortical portion the cells 
are arranged in solid columns hav- 
ing their long axes perpendicular to 
the surface of the organ. Toward 
the capsule these columns lose their 
parallel arrangement and appear in 
vertical sections as islets of cells 
surrounded by areolar tissue, the 
" zona glomerulosa." In the deep 
portion of the cortex the cellular 
columns form a meshwork and com- 
pletely lose their fascicular arrange- ^.^^^.^^^, ^^^^.^^ ^, ^^^^^,^ ^^^^^^^ ^.^„^. 

ment. This region is called the (Eberth.) l, cortex; 2, medulla; a, 

" zona reticularis. 

cells in the cortical portion are poly- 
hedral, and are frequently infiltrated 
with numerous globules of oil or fat, which give that part of the 
organ a yellow color. 

In the medulla the interstitial tissue of the organ encloses groups 
of epithelial cells, which differ from those of the cortex in being 
free from fat. Thev are also larger than those cortical cells which 
contain no fat (Fig. 163). 

The arteries of the adrenal bodies enter as numerous small twigs 
at the surface of the org-an and divide into capillaries within its 
fibrous septa. These open into a venous plexus in the medulla, 
which communicates with a single vein leaving the organ. 

The nervous supply of the adrenal bodies is very abundant. The 

rpi .1 1. 1 capsule; 6, zona glomerulosa ; c, zona epillieiiai fasclculata; d, zona reticularis; e, 
groups of medullary cells ; /, partial 
section of a large vein. 



Fig. 163. 


9 ^ 






Section through the boundary between cortex and medulla in the adrenal body of the horse. 
(Dostoiewsky.) /,/,/, cells of the cortex, infiltrated with fat-globules ; g, ganglion-cells ; 
m, epithelial cells of the medulla. 

nerve-fibres are chiefly of the medullated variety, and their bundles 
contain numerous ganglia before entering the organ. Here the 
fibres ramify abundantly in the cortex, whence they penetrate into 

Fig. 164. 

Injected lymphatics in an adrenal body of the ox. (Stilling.) L, injection-mass within the 
lymphatic vessels ; N, cross-section of a nerve : V, longitudinal section of a vein. 
Lymphatic radicles arc seen among the epithelial cells (cortical variety free from fat) 
to the right of the figure. 

the medulla. At the junction of the medulla and cortex the 
nerve-fibres are connected with ganglion-cells. The nerve-termi- 


nations arc distributed to the wails of tiie vessels and penetrate 
between the epithelial cells of" the parenchyma. 

As in the ease of the thyroi<l gland, the relations of the epithelial 
cells of the adrenal bodies to the lynij)hatics apj)ear of special 
interest. The lymphatic vessels are abundant and large, and accom- 
pany the bl(Jodvessels lying in the areolar tissue of the septa. 
Here they come into close relations with the columns of epithelial 
cells, and, at least in the cortex, send minute terminal branches 
into those columns, where they end among the epithelial cells (Fig. 
104). This arrangement of the lym})hatics appears to point to tlx; 
elaboration of an internal secretion as the function of the adrenal 
bodies. Small masses of lymphadenoid tissue are occasionally 
observed in the cortical [)ortion of the adrenal bodv. 

4. The Pituitary Body. — The pituitary body (hypophysis cerebri) 
is divisible into two portions, which differ both in their structure 
and in their eml)ryonic origins. The posterior, or nervous, lobe is 
derived from a prolongation of the third cerebral ventricle. The 
anterior, or glandular, lobe develops from a tubular prolongation, 
lined with epithelial cells, from the buccal cavity of the embryo. 
This partially or completely invests the nervous portion of the 
body, but its chief bulk is situated in front. The connection with 
the buccal cavity is obliterated, and, in the further development of 
the detached ])ortion, a number of anastomosing columns of epi- 
thelial cells are formed, which are separated from each other by 
septa of vascular areolar tissue. These septa become continuous 
at the periphery with a thin fibrous capsule furnished by the pia 

The cells of the epithelial strands in the glandular lobe appear 
to be of two sorts, which, like those in the thyroid gland, probably 
represent different stages of functional activity. The darker sort 
of cell yields microchemical reactions resembling those of colloid ; 
and little masses of colloid, presumably derived from those cells, 
are of not infre([ucnt occurrence within or at the margins of the 
epithelial columns (Figs. 165 and 166). 

The glandular lobe is richly supplied with capillary bloodvessels 
in intimate relations with the epithelium, from which they often 
appear to be separated by only a thin basement-membrane, and the 
existence of this is doubtful in some situations (Fig. 167). 

The above description shows that the structure of the hypophysis 
is similar to that of the other ductless glands alreadv considered. 



Fig. 165. 




Section from the hypophysis of the ox. (Dostoiewsky.) v, veins ; a, alveoli or cell-columns, 
with pale, relatively clear cytoplasm ; 6, alveoli or columns of darker granular cells. 
Other cell-groups contain both varieties of cell. 

Fig. 166. 

Section from the glandular lobe of the liypophysis : horse. (Lothringer.) Showing the 
darker cells at the periphery of the epithelial strands, and the clearer cells, for the most 
part, in their centres. 



Its function is still vcrv ohsciirc ; hut it appears, in cases of" exjteri- 
mental thyroidectomy and in disease of the thyroid in the lininan 
subject, to enlar<2;e when the function of the thyroid ^land is abol- 
ished and to assume vieariously the duties of that org'an. In how 
far this points to a normal similarity in function of the two orj^ans 
must, at present, he left undetermined. In cases of enlar<2:emcnt 
of the pituitary body prolound changes in nutrition, characterized 
chiefly by overgrowth, frequently take place in the bones of the 
skeleton (acromegaly). 

The nervous supply of the anterior lobe consists of non-medul- 

Fiff. 167. 

Section from the glandular lobe of the hypophysis; ehiUl six months old. (Lothringer.) 
The close relations between the epithelial cells and the capillary bloodvessels, and the 
differences in the cells, are indicated in this figure. The red blood-corpuscles within the 
capillaries have been stained dark. 

lated fibres, destitute of ganglion-cells, which ramifv about the 
ve.s.^els and send .some of their terminal twigs between the ej)ithelial 

The posterior lobe consists of tissues resembling those of the 
central nervous system : ganglion-cells, non-medullated fibrils, and 
neuroglia-cells. Within its substance there are also peculiar oval 
bodies surrounded by nervous terminations, to which sensory func- 
tions have been attributed, and sniall follicles, lined with cubical 



5. The Thymus. — This organ reaches its fullest development at 
about the second year of life, after which retrograde changes, end- 
ino- in the substitution of fibrous and adipose tissues for its proper 
structure, take place. Its development begins as an ingrowth of 
epithelium from the branchial clefts. This epithelium forms a 

Fig. 168. 

Two concentric corpuscles of Hassall, from the foetal thymus. (Klein.) 

branching, solid column of cells surrounded by embryonic connec- 
tive tissue, which develops into lymphadenoid tissue. In the 
meantime the epithelial strands are broken up and the whole organ 
becomes converted into a structure resembling a collection of lymph- 
follicles, but with this difference : that remnants of the epithelial 
strands remain in the centres of many of the follicles, where their 

Fig. 169. 

Lobule from the thymus of a child. (Schilflfer.) tr, trabecula; o, norlulc of denser lymph- 
adenoid tissue at periphery ("cortex"); 6, 6, sections of vessels within the less dense 
1 ymi'liii'icnoid tissue in the centre (" medulla ") ; r, c, concentric corpuscles of Hassall. 

cells l)ecome flattened and imbricated. These ejiithclial masses 
are known as the concentric corpuscles of Hassall (Fig. 168). 

The thymus is enclosed in a fibrous capsule, which penetrates its 
substance, dividing it into lobes and lobules. Each of these lobules 
closely resembles a lymph-follicle, but it is doubtful whether lymph- 


sinuses, corresponding to tliose in llic lyni|)liatic! nodes, are present 
in tile tliynuis (Fig. 169). 

Tile function of tlie thymus is still a mutter of doubt. It lias 
been regarded as t)ne of tlie sites in wiiieli red blood-corpuscles are 
formed, and also as a temporary lympliadenoid organ playing the 
part of the l^niph-nodes until these have become fully developed in 
other parts of the body. 

The thymus is connected with the thyroid by a strand of thymus- 
tissue, and isolated thymus-lobules arc found embedded in the 
edges of the thyroid, near the j)aratliyroid Ixxly (see Fig. 159). 

The bloodvessels ramify in the septa of the organ and send 
branches into the lymphoid follicles. The lymphatic vessels accom- 
pany the bloodvessels and surround the lobules, but do not appear 

Fici. 170. 

K/ - --^ 

Section of the carotid sjlaiid and carotid arteries near tlieir origin. (Marchand.) «", internal 
carotid; ce, external carotid; glc, carotid gland ; I, I, groups of epithelial cells; i, fibrous 
tissue between the epithelial groups; g, bloodvessel. Numerous vessels are also seen 
within the gland. 

to ]icnetrate into the lymphndenoid tissue. The nerves are small 
and not numerous. They accompany the bloodvessels, but nervous 
terminations have not been traced as distributed to the lympliade- 
noid tissue. 

The involution of the gland appears to be accomplished through 




Portion of the same gland as Fig. 170, more highly magnified ; x>, 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- 


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. 



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 




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 


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. 


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 


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, 

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. 


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, 

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 



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 

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 



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 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 



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. 



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. 




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 




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, 






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- 

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, 


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(lin<r the 
ovum formint; the "discus prolij^erus," and those lining; the sac the 
" tunica granulosa " ; hut they blend with each other at one point on 
the wall of tlie follicle, so that the ovum retains a fixed position. 
Meanwhile the tissue oi' the stroma undergoes modifications which 


Graafian follicle and >tn>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. 


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. 


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 


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 



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 

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 



suhstaiico, in wliitili fibres ciin be distinguished only with (Jilheulty. 
The siirfSice <tf" thi; nuieoiis ineinbnme is (covered uith a hiyer of 
ciliated eolinnnar epilheliiini, wliieh is coutiiiiied into lon^ tub- 
ular glands penel rati III;- (he sn|)erHeial j)orti(jns of the niuseularis 
niucosie, where they frequently branch before terminating^ in blind 
extremities." It should be borne in mind (hat at the extremities of 
these glands the whole tubule is often filled with epithelial cells, so 
that no lumen is visible. In their course into the mucous mem- 
brane these glands are usually straight at first, but in their deeper 
portions become tortuous (Figs. 190 and 191). 

Fig. 190. 

Section tlirougli tlie utriiiic wall of a rabliit, near one of the cornua. (Schiincr.) ?», Rlnnd- 
iilar portion of the niucotis membrane; m, m, muscnlaris mucosa'; a, sulimueosa of are- 
olar tissue, containing the large bloodvessels which send branches into the stroma of the 
mucous membrane; cm, circular layer of the muscular coat; Ini, longitudinal, thicker 
layer of the muscular coat ; s, serous coat, derived from a reflection of the peritoneum. 

During the cliildbearing period of life the portion of the mucous 
membrane resting upon the mu.scularis mucosae is the seat of active 
changes which pass through a cycle corresponding to each men- 
strual period, but interrupted by a special series of changes during 



pregnancy. These changes are of importance in their bearing upon 
the pathology of the organ, and must be briefly described. 

At the menstrual period the superficial portion of the mucous 
membrane, down to its muscular coat, suffers a degeneration, which 
results in its disintegration and discharge, along with some blood 
derived from the exposed and damaged vessels of small size within 
its tissues. After this degeneration the membrane is restored by a 
proliferation of the elements contained between the bundles of the 
muscularis mucosae, the glands being reformed from the remnants 
of their deep extremities. The mucous membrane slowly continues 

Fig. 191. 

Section of the human uterine mucous membrane parallel to its surface. (Henle.) 1, 2, 3, 
uterine glands in cross-section. In 2, the basement-membrane alone is represented, the 
epithelium having fallen out of the section. 4, bloodvessel in longitudinal section. Be- 
tween these structures is the highly cellular stroma of the mucous membrane, only the 
nuclei of its cells being represented. 

to increase in thickness and the glands in tortuousness until the 
next menstruation, when the same process is repeated. It will be 
noticed that the connective tissue of the mucous membrane, in the 
absence of pregnancy, is subject to periodical degeneration and re- 
generation, Avhich probably prevent its development into a mature 
fibrous tissue with an abundance of fibrillated intercellular substance. 
If an ovum, discharged from the ovary, becomes fertilized, the 
menstrual cycle of changes in the superficial portion of the mucous 
membrane of the uterus is interrupted. That portion of the rau- 
cous membrane then undergoes extensive modifications in structure 
during the early months of the ensuing pregnancy. The inter- 


cellular tissue between the uteriue glands becomes more hyper- 
plastic than ilurinj^ the intervals separating the menstrual p(!riods, 
and at the same tiuie the cells composing it become hypertrophied, 
until they closely reseuible large epithelial cells. These cells have 
been called " decidual cells." The ovum, when it reaches the 
cavity of the uterus, becomes embedded in this tissue, which grows 
around and encloses it, after which it is differentiated into three 
portions. The i)art beneath the ovum is called the decidua sero- 
tina; that which iuvests the ovum, the decidua reflexa ; and that 
lining the rest of the uterine cavity, the decidua vera. While the 
decidual tissue is developing and its cells enlarging the uterine 
glands suffer changes. Their mouths become widened, and their 
lower portions down to the muscularis mucosae dilated, after which 
the epithelial lining atrophies and seems to disappear, so that the 
lumina of the glands appear as s})aces in the decidual tissue. As 
the ovum enlarges, the decidua reflexa comes in confact with the 
decidua vera, and the two layers exert a mutual pressure upon each 
other, which flattens the spaces they contain and may obliterate 
many of them. The decidual tissue now consists of a number of 
flattened spaces M'hich are separated from each other by thin walls 
of fibrous tissue produced by the further development of the de- 
cidual tissue. The decidua reflexa and the decidua vera blend 
with each other to form a part of tlie membranes that are expelled 
from the uterus, along with the placenta, after the birth of the child, 
the rest of the membranes and most of the ])lacenta being derived 
from the foetus. After the birth of the child and the expulsion of 
the membranes the mucous membrane is regenerated from the tis- 
sues remaining in the superficial layers of the muscularis mucosEe. 

The mucous membrane of the cervical portion of the uterus does 
not participate in these changes incident to menstruation and ])reg- 
nancy, and the connective tissue underlying its epithelial lining is 
more fibrous in character than that in the corresponding part of the 
uterine body. About the middle of the cervical canal the ciliated 
epithelium, which is continuous with that of the body, passes into 
a stratified ejiithclium, which extends over the cervix uteri, the 
portio vaginalis, and the inner surface of the vagina to join that of 
the epidermis ujion the labia minora. The fibrous tissue beneath 
this stratified epithelium possesses papilla? similar to those upon the 
skin, and contains mucigenous glands, which secrete a tenacious 
mucus serving to close the cervical canal during pregnancy. The 



orifices of these glands sometimes become occluded, causing a cys- 
tic dilatation of the acini, due to accumulated secretion, " ovula 

The muscular and other tissues of the uterine wall undergo 
hypertrophy during pregnancy, the individual muscular fibres be- 
coming as much as thirty times their original bulk in the non-preg- 
nant uterus. The bloodvessels also enlarge and acquire thicker 
walls. These retain much of this increase of size, even after the 
involution of the uterus following parturition, but the muscular 
fibres suffer a partial fatty degeneration, which restores them to 
nearly their original condition. 

4. The Vagina (Fig. 192). — The subepithelial fibrous coat of the 
vagina is covered with small papillse, which project into the epithe- 

FiG. 192. 


- ■■ 

Portion of a longitiulinal seclnni of ilic va-iiuil w.ill. (lienda and Ouenlhcr's Atlas.) a, 
stratiiiud opitlielium ; b, suljupithulial areolar tibKue ; c, inucosit; ; (/.areolar 
sul>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 


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 


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- 


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 



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. 


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. 

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). 



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. 


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. 


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 



Fig. 197. 

open into the iulLiti'ubccular spaces, ili>cliarj[^iii<r l)l(»<><i into thuse 
enormously dilated venous radicles. Here 
and there arterial twigs, surrounded by an 
investment of fihrous tissue, i)roject from the 
trabeeuhe into the venous spaces. These, 
because of their twisted forms, have received 
the name hclicine arteries (Figs. 107 and 198). 
The structure of the corpus spongiosum is 

Fig. I'J".— St'ction of injected corpus eavernosum. (Henle.) a, fibrous capsule ; 6, trabeculse ; 

c, section of the arteria profunda penis. All the spaces are filled with the material used 

for injection. 
Fig. 198.— Helicine arteries. A, B, C, from the corpus eavernosum; D, from the corpus 

spongiosum ; * *, fibrous bands forming a part of the trabecular network. 

similiar to that of the corpora cavernosa, but the trabeculre are 
more delicate and the spaces between them of more uniform size. 
Its sheath is studded with papillse where it covers the glans, at the 
edge of which they are unusually large. They are covered with a 
layer of stratified epithelium, which conceals them over the surface 
of the glans, Avhere they are comparatively small, but merely invests 
the larger ones at the corona. This layer of epithelium is continu- 
ous with that of the skin covering the rest of the penis, which is 
elsewhere loosely connected with the underlying structures by 



areolar tissue devoid of fat. The skin is without hairs on the ante- 
rior two-thirds of the penis, but contains sebaceous glands, which 
are especially numerous in the fold of the prepuce, where it is 
attached near the corona of the glans, glands of Tyson. 

2. The Prostate. — This ])ody is regarded as the analogue of the 
uterus, its utricle corresponding to the cavity of that organ. It has 
a fibrous investment, which merges into the areolar tissue connect- 
ing the prostate with the surrounding structures and, in its deeper 
portions, contains smooth muscular tissue, which accompanies it in 
forming the stroma of the organ. Within this stroma are the 
prostatic glands, composed of acini, lined with epithelium of the 
columnar variety, and opening into a series of ducts having their 
orifices in the floor of the urethra. The glandular alveoli frequently 
contain little concretions of a substance closely resembling amyloid, 
corpora amylacea, which often display a marked concentric lamina- 
tion (Fig. 199). 

Fig. 199. 

Section of the prostate. (Ileitziniinn.) Sections of one acinus and portions of three others 
are included in the figure. These are surrounded by fibrous tissue traversed by bundles 
of smooth muscular fibres. E, epithelial lining of the acini; M, M, smooth muscular 
tissue ; C, concretions of amyloid material, showing concentric lamination. 

The two ejaculatory ducts pass through the ])rostatc to open into 
the urethra in its course within that organ. A little behind their 
orifices is tiie verumontanum, containing erectile tissue, which is 


suj)p<).se<l, (hirinj^ erection, to serve as u dam, preventing the entrance 
of semen into the bladder. 

Tlie ejacnlatorv ducts divide l)ehind the prostate, one branch 
forming; tlie duct of the seminal vesicle, while the other becomes 
continuous with the vas deferens. 

3. The Seminal Vesicles. — These are tubular sacs ending in blind 
extremities, with o<rasional saccular iu'auches given off from their 
sides. They are lined with a mucous meml>rane 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 



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 

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 



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® ^. 


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 

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 " 



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 


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. 



Fig. 204. 






Kio. 205. 

-^ 1 ■ r,- '-\' 


^<2>.' • 

h 16 

«-■ 4 ./' w 

Fig. 207. 

ii^iVTONi/fS— SI) 33 


i|^H'|f^^L_/( IS 

Fig. 209. 


f w8 w 


Fig. 210. Fig. 21L 




t/^y ^.A 



/ to IV 9 w 

) \ 



Fig. 212. 

w w 10 / 

Fig. 213. 




«' iy f 



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- 

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 


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 


:.!»?. •' 



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 



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 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 



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 




to the periphery, aintrif'iij^al irnj)iil<os, form the axis-cylinders of 
some of the nerves. 'J'he axis-eylinders of tliose nerves which 
convey impulses iVoni the periphery toward the nervous centres, 

Fig. 217. 

Sketch illustrating the composition of neurons. T, a neuron transmitting centrifugal 
impulses. II, a neuron receiving and transmitting centripetal impulses. Ill, a neuron, 
the function of which is supposed to be the distribution of impulses within the nerve- 
centre in which it is situated, a, ganglion-cell ; 6, dendrite ; r, teledendrites ; d, neurite ; 
e, collaterals ; /, teleneurites. In II the body c re{)resents some sensory organ im7)arting 
nervous impulses to the teledendrites of a sensory nerve. The nervous filament ^ is a 
neurite, presumably derived from the sympathetic nervous system, leading to teleneu- 
rites applied to a ganglion-cell, a, of a posterior spinal ganglion. The portion h of the 
"nerve" springing from that cell is regarded as a portion of the cell itself. In the 
embryonic condition the dendrite and neurite both spring directly and separately from 
the body of the cell, the portion /( being a subse<iuent development, i, endothelial 
envelope surrounding the ganglion-cell. Ill represents a ganglion-cell, apparently devoid 
of distinct dendrites, but having numerous processes that at first ai)pear protoplasmic, 
but soon assume the characters of neurites. These cells are found in the retina and 
olfactory bulb, and have been termed spongioblasts, cellulas amacrinas, and parareticu- 
lar cells. It is thought that nervous stimuli are received directly by the cytoplasm of 
the cell, without the intermediation of dendrites, x represents the omission of a portion 
of a fibre. The arrows indicate the directions taken by nervoiis impulses. 

centripetal stimuli, may be the dendrites connected with ganglion- 
cells in or near those centres ; r. r/., in the posterior root-ganglia of 
the spinal nerves, or they may be the neurites springing from 



peripheral ganglion-cells, as is exemplified in many, if not all, of 
the organs of special sense. 


The axis of the spinal cord is composed of a column of gray 
matter containing numerous ganglion-cells and nervous filaments 
held in position by a cement-substance, neuroglia-cells, the fibrous 
prolongation of the ependyma cells lining the central canal, and a little 
fibrous tissue accompanying the vessels derived from the pia mater. 

Fig. 218. 

Figs. 218 and 21'.).— Tmnsverse .sections of human spinal cord. (.Scliiifcr.) 
Fig. 218, from the lower cervical repion ; Fig. 219, from the middle dor.sal region, n, b, c, groups 
of ganglion-cells in the anterior horn; d, cells of the lateral horn; e, middle group of 
cells ; /, cells of Clarke's column ; (/, cells of posterior horn ; c, c, central canal ; a, c, an- 
terior commissure of white matter. 



Fki. 2-2(1 


Transverse section of human spinal cord, from the middle lumbar region. (Schiifcr.) a h, c, 
groups of ganglion-cells in the anterior horn ; d, cells of the lateral horn ; r, middle 
group of cells ; /, cells of Clarke's column ; g, cells of posterior horn ; c. c, central canal ; 
o, c, anterior commissure of white matter. 

In cros.s-section this column of gray matter present.s a tran.« 
central portion, the gray commis.'^ure, near the middle of 'which is 
the central canal. At each side this gray commissure blends ^vith 
masses of gray matter, occu]n'ing nearly the centre of each lateral 
half of the cord and haying a general crescentic form. The ends 
of these crescentic masses form the anterior and })osterior cornua 
of the gray matter, from Nvhich the anterior and posterior roots of 
the spinal neryes proceed. The anterior cornua are larger than the 
posterior and contain larger ganglion-cells. 

Surrounding the column of gray matter eyerywhere, except at 
the bottom of the posterior median fissure of the cord, and the 
interruptions formed by the nerye-roots in their exit from the gray 
matter, is a layer of white matter, formed of medullated nerye- 
fibres running parallel with the axis of the cord and held together 
by neui'oglia and delicate yascularized fibrous bands proceeding 
from the deep surface of the pia mater. 

The ^vhite matter of the cord has been diyided into a number of 
columns, for the mo.>^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 



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 


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 



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 



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- 




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- 


dendrites of tlie cells in the anterior liorn, especial ly those which 
give off neiirites to the anterior roots of the spinal nerves (Fig. 

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. 


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, 



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- 



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. 


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. 


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- 



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. 


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- 

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 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- 



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 


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. 



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." 



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 



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 

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, 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 



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 


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. 


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 

Fig. 239. 



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." 


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 



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 


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 

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 



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. 


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 


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. 


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. 

<S. The eighth layer contains those ganglion-cells wlK>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. 




As the result of disturbances in the internal economy of the cell, 
a variety of changes, called degenerations or infiltrations, are occa- 
fiinnedj s pme of whin h 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. 



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 

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 



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). 



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. 


)!■ <S^ — S^e'.cs...<s>"jj>- C 


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 <lcgcu( ration may also be the result 


of toxic conditions that arc not accompanied by rise of tempera- 

Ill all the foregoing cases the cause is of an acnte nature, acting 
rapidly on the cells. If that actiim be moderate in degree aiid |}cr:- ) 
sistent, the albuminoid degeneration passes into fatty degcuiLraikm. 
Hence the tatter has been called *' chronic parenchymatous inflam- 

]5ut fatty degeneration is not always preceded by albuminoid 
degeneration. It is found widely distributed in the cells of the 
body in ansemia (Fig. 247), leucaemia, and phthisis, and in many 

Localized fatty deKcnoration of the cardiac muscle in a case of pernicious ansemia. (Birch- 
Ilirschfeld.) The three or four fibres at the bottom of the lisnre are nearly, if not quite, 
normal. The rest of the fibres are the seat of an extensive fatty degeneration, resulting 
in a complete obliteration of the normal striations of the contractile substance. Section 
of the fresh, unstained muscle. The nuclei, being unstained, are but faintly visible in 
such sections, and arc not represented. 

toxic conditions that are of a subacute or chronic character. In a 
more localized form it follows those diseases of the bloodvessels 
which interfere with a normally abundant supply of blood to the 
])arts in which they are distributed. It appears, again, in parts the 
functional activity of which is markedly increased without a corre- 
sponding increase in the nutrient supply. For example, in stenosis 
of an orifice of the heart, when extra work is thrown on the cardiac 
muscle and the nutrient supply is insufficient to permit of hyper- 
trophy, the muscle-cells suffer fatty degeneration, and the conse- 
(pient weakening of its walls results in dilatation of that ])articular 
cavity which is subjected to the difHcult task of urging the blood 
through the narrowed orifice. 

If we examine these various conditions with a view to determin- 
ing their effects upon the cells, we shall find that they have one 
--common -feat^re^ There is in all of them a lack of balance between 
the nutrient suppl)[_of which tlu^ cells can avail tbemselvBS and 


the consumption of material made necessary by th e work ^ required 

Under these circumstances the cells appear, first, to utilize the 
food-materials which they already contain as an accumulated stock 
(metaplasm) ; but when these are exhausted they are forced to draw 
upon those materials which exist as a part of their own organized 
structure, if they are to maintain their functional activities. They 
thus sacrifice the integrity of that structure in order to do the work 
that has been assigned to them in the organization of the whole body. 

Now, there is a difference in the immediate availability of the 
various classes of foods. The carbohydrates appear to be the most 
susceptible of rapid utilization ; the proteids come next, and the 
fats last. We may imagine, then, that in a sudden emergency the 
cells will first consume the greater part of their store of carbo- 
hydrates, then the proteids, and lastly the fats. If the condition 
be an acute one, so that a part of the organized proteids are utilized 
as food, this utilization is not complete, but the proteids are split 
up into a portion that can be most readily oxidized and turned ta 
account, and a residual portion, which appears in granular form 
within the cytoplasm. 

We may also imagine that, in its efforts to obtain adequate 
nourishment, the cell imbibes an excessive amount o f_fluid_from 
its surj]qundijigs. 

If the adverse circumstances are extreme, the nucleus is alsa 

/ 1 overworked and relatively starved, and suffers in its integrity 

(karyolysis). When the nucleus^ is destroyed, or when there is no^ 

j-^longer sufficient cytoplasm to aid it in Itsjissimilatiyej unction, a 

ref^vj?ry _of jhe cell becomes imp ossible. ' 

Let us now consider how this conception of albuminoid degen- 
eration may serve to explain its occurrence in the various conditions 
in which it is found. 

In fevers the rise of temperature is evidence of an increased 
metabolism within the body — i. c, the cells of the body are more 
active in bringing about chemical changes. The amount of urea 
eliminated from the body is also increased, showing that those 
chemical changes involve an additional consumption of proteids. 

In febrile conditions, then, the cells are unusually active and con- 
, sume an increased amount of proteids. Xi£t-ii!!LiLext jnquir e wh a t co xu^- 
t'_ditions exist which are likely to interfere with their nutrient supply. 

The source of all nourishment, which is not gaseous, being the: 


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- 


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 cy toplasm, 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, 


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 _ox ulations 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<i-en in the blood. This is luuuifest-iiLcaaiiiJif- 
.aiKiinia, n.lvauccd phthisis, and |)oisonin<;- with carbonic oxide^hi^h — -^ 
(l(v<tr<)ys the respiratory value of the ha^muglobiu. 

In the subacute and chronic toxic conditions — e.g., such cases of 
poisoning by phosi)horus or arsenic in which the patient survives 
for a considerable time — the blood probably contains a sufficiently 
abundant supply of oxygen for the needs of the tissues. But intra- 
cellular respiration is a complicated process ; not a simple and direct 
burning of substances occasioned by their immediate conversion into 
fuUv oxidized compounds when brought into relations with free 
oxygen. The food-materials are split up within the cell into com- 
pounds of simpler constitution, some of which receive a sufficient 
amount of oxygen, from the original material of which they are 
derivatives, to satisfy their affinities, and are, therefore, stable; 
while others are organic substances in a chemically reduced state, 
which unite with the free oxygen that may be accessible. The oxi- 
dation is not caused by the presence of free oxygen, but is an inci- 
dent in the chemical changes carried on by the cell. 

In the toxic conditions leading to fatty degeneration this intra- 
cellular oxidation is probably interfered with through the action of 
the poisons upon the cytoplasm, and, as a result, the least easily 
oxidizable substance, fat, remains as an unutilized residue. The 
])()isons at the same time probably interfere with the nutrition of the 
cell, which draws upon its organized proteids for a supply of nitro- 
gen, leaving again a remnant of unavailable fat. 

It is easily comprehensible that relative overwork may have the 
same effect upon the cell as relative innutrition. The fatty degen- 
eration of the heart-muscle as the result of stenosis or of valvular 
insufficiency at one of its orifices would, therefore, be explained as 
an example of a lack of balance between the sup])ly and consump- 
tion of food in the economv of the cardiac cells. Relative overwork 
of the heart is also one of the effects of marked anaemia. The 
ansemic condition involves a diminished supply of oxygen, from 



which the heart, as well as the other tissues, suffers. But the 
demand for oxygen on the part of the general economy requires an 
acceleration of the circulation ; this throws extra work upon a 
relatively starved heart. 

It is evident, from the foregoing considerations, that albuminoid 
and fatty degenerations must be very common conditions in the cells 
of the body. Their close etiological similarity makes it obvious, 
also, that they must very frequently be associated with each other, 
either in the same cell or in different cells of the same organ. The 
fact that fatty degeneration is often a sequel of albuminoid degen- 
eration may be explained as the result of a toxic or other condition, 
which has been sudden in its onset, but has declined in intensity 
with the lapse of time. Or it may be possible that the cells are 
able gradually to adapt themselves, in a measure, to the new con- 
ditions under which they must do their work, and that they become 
able to utilize more completely the foods they receive ; leaving a 
fatty, instead of an albuminoid, residue. 

Fatty degeneration, like albuminoid degeneration, may lead to a 
total destruction of the cell, • leaving the fatty globules free, or 
recovery may take place on the subsidence of the cause. 

2. Cheesy degeneration is a term applied to an association of 
albuminoid and fatty degenerations with necrosis, in which the 
detritus of the tissues forms a dry material, somewhat resembling 
the softer varieties of cheese. Under the microscope this cheesy 
material has a finely granular appearance, with here and there small 
fragments of nuclear chromoplasm Avhich still retain their affinity for 
nuclear dyes. 

3. Fatty Infiltration. — Essentially different from fatty degenera- 
tion is an accumulation of fat in cells as the result of their over- 
feeding. It may be due to an excessive reception of fat by the 
cells, but this is not necessarily the case. A supply of any form 
of food that is in considerable excess of the needs of the body may 
result in a fatty infiltration of its cells, for fat is the least readily 
consumed variety of food, and where the other varieties are in 
great abundance it may be guarded against destruction and remain 
in the tissues. Furthermore, a part of the excess of other food- 
materials may be converted into fat within the cells and be retained 
by them. 

Fatty infiltration is a normal condition of many cells. Those 
which form the characteristic element in adipose tissue (Fig. 65) are 


connective-tis.suo cells tliat have iiiidcrjiono cxtrnsivc fatty infiltra- 
tion. A transitory tatty infiltration is also normal in the cells of 
the liver (Fij;. 248). 

Fic}. 248 

Cells from the human liver, normal. (Orth.) a, cells free from fat. The isolated cell to the 
right contains two nuclei and three or four granules of pigment. The three lower cells, 
6, are infiltrated w ith globules of fat. It will be noticed that those three cells contain as 
much cytoplasm as the two contiguous cells, a. This is taken as an indication that the 
fat is superadded to the cytoplasm, and has not been prmluced at the expense of part of 
the organhed substance of the cell. This does not imply that the fat was necessarily 
taken into the cell as such, for it may have been produced within the cell from food-mate- 
rials; but it has not been produced at a sacrifice of the organized materials forming an 
essential part of the living cell. 

The sflobiiles of fat form a part of the metaplasm of the cells in 
which they are situated ; /. e., they do not constitute an integral 
part of the cytoplasm, but lie within it, leaving it intact, unless the 
iiccumulation is so great that the functions of the cell are interfered 
with. Then the cytoplasm may suffer atrophy and its usefulness be 

It is not possible to lay down any practical rule for distinguishing 
between fatty infiltration and fatty degeneration when cells are 
examined under the microscope, beyond the general statement that 
in degeneration there is a corresponding destruction of the cyto- 
plasm as the fat accumulates. In fatty infiltration the globules of 
fat are rather more apt to coalesce with each other than in fatty 
ilegeneration, so that the globules appear larger. This is not in- 
variably the ca.'ic, however, the behavior of the fat in this respect 
ditfering in different kinds of cell. 

4. Glycogenic Infiltration. — This is a condition analogous to fatty 
infiltration, but the stored excess of food-material in this case be- 
longs to the class of carbohydrates. The condition is found in the 
cells of the convoluted renal tubules in cases of diabetes mellitus, 
sometimes in the leucocytes in inflammatory foci, and occasionally 
in the cells of tumors where the functional activities of the cells 
are in abeyance and only their formative powers call for a consump- 
tion of food. * 


The glycogen occurs either in granules or in small, irregular 
masses within the cytoplasm (Fig. 249). It is soluble in water, and 
its detection is a matter of difficulty unless special methods of prep- 

FiG. 249. 

Glycogenic infiltration of the cells in an endothelioma. (Driessen.) a, cell crowded with 
granular masses of glycogen ; 6, fibrous tissue forming the stroma of the tumor ; c, space 
within the growth containing blood. Section from an endothelioma of bone, stained 
with a solution of iodine and gum-arabic in water. Iodine stains glycogen brown. The 
nuclei and cytoplasm of the cells are not represented. A section from the same tumor 
after the extraction of the glycogen and staining with nuclear dyes is shown in Fig. 222. 

aration are employed to retain it in situ and so facilitate its recog- 
nition. When it is dissolved from the cytoplasm it leaves small, 
clear, empty spaces behind. 

Glycogenic infiltration is a normal condition in the cells of the 
liver and in muscular fibres. In the latter situation it serves as a 
store of rapidly available energy, whicli can be drawn upon during 
the functional activity of the cells. In the liver it serves a similar 
purpose for tiie whole body. 

5. Serous Infiltration. — In ocdematous conditions of the tissues 
their cells sometimes imbibe fluid from their surroundings, which 
appears as clear drops or vacuoles within the cytoplasm (Fig. 250). 
The condition may subsequently subside, or it may lead to a disin- 
tegration of the cytoplasm and nucleus. The cell then undergoes 
a form of destruction very closely resembling that in albuminoid 


(lci;ciicrati()ii. Serous iuliltrution, more or less ('omj)lic;it('<l with 
;ill)iimiiioi<l (lc't>;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. 


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 


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 

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 

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.-)!. 



Fio. 252. 



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. 


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. 



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 
converte<l into the stratified variety the susceptibility to keratoid 
degeneration is an acquired character, columnar ej)itlieliiun under 
normal conditions never suffering this change. 

10. Amyloid Infiltration. — The change in the tissues known by 
this name, or that of amyloid degeneration, has many resemblances 
to hyaline degeneration (or infiltration). Amyloid differs, however, 
from the hyaline substances in being recognizable by means of a 
number of characteristic reactions, althougli they vary considerably 

Fig. 253. 

Amyloid infiltration in the liver. (Tlioma.) a, lumen of an intralobular capillarj', sur- 
rounded by the endothelial wall of the vessel ; 6, amyloid substance immediately 
beneath the endothelium ; c, epithelial cells of the hepatic parenchyma, some of which 
show a fatty infiltration. 

in sharpness in different cases, and give rise to the suspicion that 
the amyloid substance is not always of constant chemical composi- 
tion, or that it may be transformed into other substances of similar 
physical and optical properties. 

Amyloid is a nitrogenous material, which is stained a dark brown 


by aqueous solutions of iodine, while the normal tissues acquire a 
yelloNV color. Under the microscope the brown color has a marked 
reddish tinge. Solutions of methyl-violet give amyloid a red color 
and stain the rest of the tissues blue or bluish-violet. It is upon 
these reactions, and not upon the optical appearance of the material 
when unstained, that the recognition of amyloid depends. 

Its most frequent situation is in the walls of the smaller blood- 
vessels, where it lies in the deeper layers of the intima or in the 
muscular coat. It may also be deposited around the endothelial 
walls of the capillaries (Fig. 253). 

Amyloid infiltration occurs in syphilis, advanced tuberculosis 
(especially of bone), long-continued suppuration, and similar condi- 
tions in which there is j3rofound cachexia. It evidently depends 
upon conditions of marked malnutrition or chronic toxic conditions, 
and it is believed that its occurrence depends upon the inability of 
the tissue-cells to utilize the proteids that are present in the inter- 
stitial serum. These are thought to accumulate and gradually be- 
come transformed into amyloid. The deposition of amyloid, accord- 
ing to this hypothesis, w^ould depend primarily upon a lack of power 
to assimilate proteids on the part of the cells. 

The presence of amyloid between the cellular elements of the 
tissue interferes with their nutrition, and they suifer atrophy. 

11. Calcareous Infiltration (Figs. 254 and 255). — There appears to 
be a marked affinity between necrosed tissues, or tissues of low vital- 
ity, and the salts of lime that are found in the circulating fluids of 
the body, which leads to a deposit of the latter within those tis- 
sues. The cheesy material that results from tubercular or other proc- 
esses is prone to this form of infiltration. Cicatricial tissue, when 
abundant and poorly nourished, may also be the seat of lime-deposits. 
Similar deposits are sometimes associated with those of urates in the 
inflammatory nodules of low vitality that characterize gout. Bits 
of organic or other foreign matter that are exposed to fluids contain- 
ing salts of lime are liable to become encrusted with a coating of cal- 
careous material. This is the origin of many renal and other calculi 
and of the vein-stones that form around small thrombi of occasional 
occurrence where the circulation is very sluggish ; e. g., in the 
venous plexuses within the pelvis, or behind the valves that occur 
in the course of most of the veins. Calcification of cartilage is also 
common after the individual has attained a certain age. Tumors 
in which the tissues are of low vitality or have degenerated are 



also liable to calcareous infiltration. That infiltration appears, 
tlien, to be always secondary to some morbid process lowering the 
vitality of the tissnes. 

Calcareons infiltration may serve as a type of infiltrations with 
other mati'rials, such as urates, and of the formation of concretions ; 
for exampW, gall-stones. These and 
other concretions contain a nucleus of 
organic or other nature, upon which 
the salts are deposited from their solu- 
tions very much as sugar crystallizes 
upon threads suspended in a syrup. 

12. Degeneration of Nerves. — If a 
nerve-fil)re be severed from its connec- 
tion with the ganglion-cell of which it 
is a process, it suffers disintegration. 
The medullary sheath breaks up into 
a number of globular masses, which |-|^I^I 
are subdivided and eventually ab- 
sorbed. The axis-cylinder becomes 
swollen, granular, and also disappears. 
If the ganglion-cell retains its vitality. 

Fig. 254. 

Fig. 254. — Calcareous infiltration of renal <?lomcriili, secondary to hyaline degeneration of 
the capillary walls, obliteration of the vascular lumen, and death of the tissue. The 
glomerulus to the left shows a slight granular deposit of calcareous material in the 
hyaline glomerulus. The figure to the right shows the organic base almost completely 
obscured by calcareous granules. (Ribbert. i 

Fig. iio.— Calcareous infiltration of the cardiac muscle. (Langerhans.) a, degenerated car- 
diac muscle; b, muscular fibres impregnated with lime-salts. The specimen was taken 
from a case of chronic lead-poisoning. The cells which are the seat of the calcareous 
infiltration must have been dead for a considerable time before the death of the indi- 

it may regenerate the nerve by the development of a new process. 
If, however, the ganglion-cell has been destroyed, regenerati(»n does 
not take place. This exemj)lifies the statement, made in the chapter 
on the cell, that portions of cells which were devoid of a nucleus 
could not continue their existence. 



Atrophy is a diminutiou in the size of a part, due to a deficient 
nutrition of its constituents, whicli is neither so rapid nor so destruc- 
tive as to cause necrotic, degenerative, or inflammatorv changes. 
The tissue-elements appear comparatively normal under the micro- 
scope, but are either all or in part diminished in size. This dimi- 
nution in size is frequently accompanied by an increased depth of the 
usual coloring of the tissue-elements, or with the appearance of 
granules of pigment (Fig. 256). 

Fig. 256. 

Brown or senile atrophy of tne heart. fRibbert.) The muscle-fibres are reduced in diameter. 
At the ends of the nuclei are collections of pigment-granules. 

The cause of atrophy may operate almost directly upon the cells 
involved, or it may indirectly influence the nutrition of the cells 
through le.sions in the circulatory or nervous system, or through an 
interference with the processes of general nutrition maintaining the 
whole body. 

1. Functional Atrophy. — It appears to be a general principle gov- 
erning living organisms that functional activity, within a certain 
normal range, is necessary to the maintenance of the normal nutri- 
tion of a part. When the required degree of functional activity 
is not called forth, the nutrition of the part suffers and it undergoes 
atrophy. Paralyzed muscles their normal size through innutri- 
tion following their disuse. Secreting glands may also suffer atrophy 




wlicn there is no longer an a«Ie(|uute call tnr tlifir functional activ- 

This form <>f 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. 


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 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. 


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 


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). 


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- 

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. 


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- 



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 

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. 





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 



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 

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- 



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 

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 


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 


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- 


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 only an 
evanescent irritation which does not 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 


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 

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- 



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. 


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 particles are the 
leucocytes, which are lighter than the red corpuscles, and, as the 


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- 


eytes. This is particularly tin- case when the cause of the inflam- 
mation is an infection with bacteria. Under those circumstances 
the leucocytes that enii<j::rate from the hlood accumulate in great 
numhers in the tissues around the site of injection. 

The leucocytes, by their passage through the cement between the 
en(li>th('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 



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. 







a «^ VX '^ 


*r \' 

^^ ' 



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 


rcgartk'cl as constitutiii*:; the lUdruvtire phasic ot" acute iiiHainiiia- 

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 


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 

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 



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. 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. 


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 



in the nutrition of the tissiu,'. There is a 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). 



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 

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- 


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 



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. 


^ '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 

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 


Yu.. 27.',. 


*? % 

•** S^ <* "Tr. ^^•' . 1 




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. 


\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. 


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 


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 



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. 










.^.-■'- a*' '^ ■' .• »A /-. 




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 

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. 



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 

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 


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 



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. 




h — 













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 

6. Croupous inflammation is an inflammation of a surface, char- 



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 



iio<lulos of leprosy and jj^landors, arc forms of sulKicute inflanmia- 
tion wliicli owi' tlicir jMriiliaritios to the infections tliat occasion 
tlicin. The tiihenle, caused by the presence of the tul)ercle bacil- 

Fig. 282 


Early stage of experimental tuberculosis ; cornea of rabbit. (Schieck.) Five days after 
inoculation. Rejuvenescence and beginning degeneration in fixed cells of the fibrous 
tissue, o, karyolysis in a cell affected by a group Of tubercle bacilli within the cyto- 
plasm ; b, karyokinetic figure in another cell. 

his, is the most common of these inflammations and may be taken 
as a type of the whole group. 

The tubercle bacillus does not always produce the little in- 



«.-.— ' *^ 

« o *-«» — 

^•:v-^ 4 

zj — ~iL^ 

_ ...^ « 


Early stage of experimental tuberculosis; cornea of rabbit. (Schieck.) Ten days after inocu- 
lation. Beginning of a tubercle. The " epithelioid " or young connective-tissue cells are 
masked by the presence of leucocytes with denser nuclei, which have been attracted by 
the chemotactic (positive chemotaxis) influence of the materials accumulating in the 
inflamed focus. 

flammatory nodules called " tubercles." It sometimes occasions 
a suppurative inflammation of sluggish type, forming "cold ab- 
scesses," or purulent inflammations of mucous membranes. It 


may also cause sero-hsemorrhagic exudations from the serous 
membranes — e. g., the pleura; but the most characteristic tissue- 
reaction due to its presence is the formation of the tubercle. This 
is the result of a rejuvenescence of the connective-tissue cells, 
without any preceding exudation, and an attempt at the pro- 
duction of granulation-tissue around the bacilli (Figs. 282 and 
283). These multiply so slowly that they and their products exert 
merely an irritation on the cells of the tissue, stimulating them 
to reproduce, but they do not usually cause the growth of new 
bloodvessels, so that in the majority of cases the granulation-tis- 
sue is not vascularized. Furthermore, as they increase in number 
the bacteria cause degenerative and necrotic changes in the cells 
that have been produced, and, as their products increase in 
amount, the cells in the centre of the focus of inflammation are 
destroyed (cheesy degeneration, p. 274), while those at the periph- 
ery multiply, causing an increase in the size of the inflamma- 
tory nodule or tubercle. The multiplication of the cells is often 
hindered to a certain extent by the poisons present ; the nuclei 
divide, but the protoplasm fails to undergo a corresponding di- 
vision. In this way multinucleated cells, called "giant-cells," are 

As the result of these processes a developing tubercle presents the 
following appearances under the microscope. In the centre is a 
mass of cheesy matter, composed of fine granules of fat, albuminoid 
material, and fragments of nuclei, the result of degenerative and 
necrotic changes caused by the bacterial poisons. Around this 
mass is a zone of rather large " epithelioid " cells, which belong to 
the granulation-tissue, and among which there may be a variable 
number of emigrated leucocytes, probably attracted by the necrosed 
tissues in the centre. Also, near the centre or in the granulation- 
tissue, a few giant-cells may be present ; but they are not invariably 
found, nor is their presence a conclusive sign that the process is 
tubercular (Fig. 284). 

The ultimate outcome of the process varies in different cases. 
The inflammatory reaction may overcome the infection, encapsulat- 
ing the nodule with a dense cicatricial tissue ; or the infection may 
coiKpicr ; bits of tlie cheesy matter containing tubercle bacilli may 
th(;n find entrance into the lymphatic circulation and be carried to 
the neighboring lym])h-glands, estal)lis]iing in them new foci of 
tubercular inflammation, or tubercle bacilli may get into the blood- 


vessels ami cany the infection to all parts ol" the body, occasioning 
general tuberculosis. 

The poisonous productti of the tubercle bacilli arc absorbed into 
the general systcMu, producing disturbances of nutrition, emaciation, 
and fever. Old encsapsuhited tubercular products are prone to 
calcareous iafiltratiou, but, even after prolonged encapsulation, 

Fig. 284. 

Miliary tubercle; Innj? of a horse. (Birch-Hirschtcld ami .inline.) ('licesy degeneration has 
only just bej?uu in the centre of the focus of inflammation, where the n\iclei of epithe- 
lioid cells and leucocytes arc still visible. At the periphery of the tubercle is a zone of 
round-cell or leucocytic infiltration. Throe giant-cells, with peripheral nticlei, occupy 
intermediate positions; around the tubercle are the infiltrated walls of pulmonary 

the tubercle bacilli which have been imprisoned may retain their 
vitality, and, if for any reason the poorly nourished capsule suffers 
in its integrity, these old nodules may become the source of fresh 
infection. This is a not uncommon result of some acute disease like 
scarlet fever, typhoid fever, or influenza, convalescence from those 
diseases being followed by the development of tuberculosis spring- 
ing from an old and long-dormant tubercular infection. 

In the lungs the tubercles, as they increase in size, involve the 
walls of the alveoli or the bronchi, and when the cheesy matter 



escapes into the alveoli or bronchi cavities are produced. The proc- 
ess rarely remains a purely tubercular one in the lungs. The con- 
ditions there (exposure to inspired air) are favorable to a mixed 
infection with jjyogenic bacteria, which hastens the destruction of 
the pulmonary tissues inaugurated by the tubercle bacillus. 

Isolated tubercles, such as have been described, are not infre- 
quently met with ; but it is more usual to find a number of such 
nodules in close aggregation, each starting from a distinct focus of 
infection. As these enlarge, their peripheries coalesce, and finally 
their cheesy centres meet and blend. Meanwhile fresh young 
nodules are formed around the older mass, and thus the tubercular 
disintegration of the tissues spreads. It is for this reason that 
tubercular ulcers — e. g., of the intestine — have swollen and under- 
mined borders (Fig. 285). 

Fig. 285. 

Tubercular ulcer of the intestiue. (Kaufmann.) The cavity of the ulcer was formed 
through disintegration and removal of the cheesy matter formed in the earlier tuber- 
cles. Now the base of the ulcer is formed by necrosed and cheesy material, beneath 
which eight or nine distinct tubercles are distinguishable, those in the centre extending 
into the muscular coat of the intestine. The infection has also extended into the lymph- 
atics beneath the serous coat, where three tubercles can be seen. 

The other granulomata have peculiarities due to their special 
causes, which are pretty clearly defined in typical cases ; but, as 
in tuberculosis, these inflammations may in certain instances be 
structurally indistinguishable from those due to other causes. 

Chronic Inflammation. 

A consideration of the infective granulomata makes the fact clear 
that inflammation may occur without the production of a distinct 
exudate, the damaging cause merely exciting the tissues to prolifer- 
ation ; but in that group of inflammations the excitation of the tis- 
sues was sufficiently intense to occasion the development of a tissue 
clo.sely resembling the granulations of acute inflammation. For 
this reason they were designated as fiubacute inflammations. 

There is another group of inflammations in which the irritation 
of the tissues is not sufficient to induce a rejuvenescence of the 
cells in such a pronounced degree as to cause their reversion to a 



compcirativfly imdifTcrciitiiitod condition. No <:;raiiuliition.s arc, 
therefore, produced, but tlie cells are .simply stimulated to a i'orma- 
tiv'c activity that is abnormal to the part. This is the group of 
chronic inflammations, of which three or four examples will be 

Chronic periosteal inflammation may be induced by a number of 
damaging causes of slight intensity, but repeated application. The 
response which the cells of the periosteum make to this irritation 
is a revival of their formative activity and the production of bone, 
which forms an " epiphyte," or other osseous excrescence, apparently 
springing from the surface of tlie older bone. Similar new-forma- 
tions of bone may take their origin from the endosteum, forming 

Fig. 286. 

Cirrhosis of the liver; chronic interstitial hepatitis. (Kaufmann.) a, lobules of the liver; 
6, increased interstitial fibrous tissue, the result of the inflammatory process; c, collec- 
tion of nuclei in the fibrous tissue, showing that the process is still in progress ; d, thick- 
ened capsule of the liver. 

layers that encroach upon the lumina of the Haversian canals or 
the medullary cavity of the bone. These depo.sits are more diffuse 
than those springing from the external surface of the bone, probably 
because they arise as the result of a more widespread irritation, such 
as the presence of some noxious substance in the circulation, and not 
from a localized point of irritation. 

Another example of this group is presented by cirrhosis of the liver, 


selected from among the chronic interstitial inflammations that may 
affect any of the organs of the body. In hepatic cirrhosis there is a 
redundant prodnction of fibrous tissue around the branches of the por- 
tal vein, and, therefore, appearing between the " lobules " of the liver 
(Fig. 286). This has the same tendency as other cicatricial tissue to 
contract, and that contraction causes atrophy of the hepatic cells 
through the pressure it exerts upon them. There may be another cause 
for this atrophy of the liver-cells, which will be more comprehensible 
after considering the probable etiology of the interstitial inflamma- 
tion itself. This appears to be caused by the absorption of irritating 
substances from the digestive tract, which are carried in most con- 
centrated form by the portal vein to the liver. Here they stimulate 
the cells of the connective tissue to produce fresh fibrous tissue 
around the branches of that vessel. But it is quite possible that 
those same substances may act injuriously upon the parenchymatous 
cells of the liver, impairing their nutrition and rendering them 
especially liable to atrophy under the increased pressure from the 
fibrous tissue in their neighborhood. 

While the interstitial inflammation is in progress the connective 
tissue of Glisson's capsule a})pears not only increased in amount, 
but more highly cellular than normal. This is due in part to a 
multiplication of the fixed cells of the fibrous tissue, in part to 
a round-cell infiltration — i. e., an immigration of leucocytes. This 
immigration is more abundant in some cases than in others, as would 
be expected, since the process must be subject to exacerbations, due 
to fluctuations in the amount of the irritating substances brought to 
the liver. In fact, we should hardly expect to find a sharp division 
between the slowest chronic inflammation and such inflammations 
as approach the character of a subacute manifestation of the same 

A third example of the chronic inflammatory process may be 
found in tlie reaction of the tissues around the necrotic mass result- 
ing from bland embolism. Suppose one of the vessels of the kidney 
to be [)luggcd by an aseptic body. The tissues normally supplied with 
blood through that vessel will die (Fig. 293). But the presence of 
this dead tissue, although it contains no micro-organisms, acts as an 
irritant upon the surrounding tissues, which respond by the produc- 
tion of a capsule of fibrous tissue. The necrosed tissues may 
remain within this capsule, or they may be absorbed, in which case 
the capsule shrinks to a ])uckcring mass of dense fibrous tissue. 



In like manner a non-inf'ecticKis f()rei<i;n body may become 
lated witliin any of the tissues of tiie body. 

Still another example of chronic interstitial inflammation appears 
to be furnished by cases in which the parenchyma has suffered 
atrojihy or some other form of destruction, and the loss is made 
good by the production of fil)r(^us tissue without a precedent forma- 
tion of granulatious. In embolism of a branch of one of the 
coronary arteries supi)lying the heart-muscle the destruction of the 
muscle-tibres seems to stimulate the f(n*mative activities of the cells 
of the interstitial fibrous tissue. The deduction that the production 
of fibrous tissue is the direct result of a loss of parenchyma is, how- 
ever, not quite clear, for the stimulus to tissue-production may 

Fig. 287. 

.Y\^^^ -»«>&»*? '^_?**3*V>. 


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. 


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. 


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 



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 


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- 


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 


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. — 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 


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, 

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. 

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, 


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 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. 



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 


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- 

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. 


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 



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. 






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 


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 



!M(i :!M(i. 



ip. <ry^ 

Section of regenerating liver, (v. Meister.) 

iilso atfectod by a degenerative process; but otliers rejuvenate, mul- 

FiG. 302. 

FiG. 301. 





Phases in the rcKeneration of a tendon ; guinoa-pig. (Enderlen.) 
Fig. oOl.— Two days alter section : o, swollen intercellular substance ; 6, karyolysis ; c, d, leu- 
cocytes; e, karyokinesis. 
Fig. 302. — Seven days after section : a, nucleus of young connective-tissue cell ; 6, karyoki- 
nesis; c, intercellular substance of new formation. 

tiply, and eventually ])n>duee a highly cellular tissue, which devel- 
ops into tendinous fibrous tissue (Figs. 301, 302, and 303). 



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? 


t ff 


•fc H III , 


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 



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 



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. 

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. 


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, 



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 

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 


arranged in a manner usually quite unlike that of any normal 

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- 

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 


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 



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. 


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- 

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 



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 



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 




f^*^ " 



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 

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 fibrom- 


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 



Fi(i. 312. 


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. 



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 


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 



bio for fraf>;rncnts of cartilage to become detached from the primary 
growth and appear in the secondary tumors, shotdd metastasis 

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- 




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). 


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 

Fig. 319. 




ft F 


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 

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 



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 



the case and the structure and evidences of proliferation presented 

by tlie tumor itself. 

Fig. 822. 






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. 



~^, -^^' 

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- 


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 <legrces of malignancy, beginning with 
those that are most malignant, and have little intercellular sul)stance, 
and cells which are only slightly, if at all, differentiated, and end- 
ing with those that can hardly be considered malignant, and which 
have such an abundant fibrous intercellular substance that their 
structure closely agrees with that of fibroma. In fact, no sharp 
line between these sarcomata and the fibromata can be drawn. The 
two classes of tumor merge into one another : they have the same 
origin, and differ only in the behavior of their cells in the exercise 
of their formative activities. Those differences are, however, of the 
utmost clinical importance. 

The sarcomata are classified, according to the characters of 
their component cells, into the round-cell, spindle-cell, giant- 
cell, melanotic, etc., varieties. They are also subdivided ac- 
cording to the way in which those cells are arranged. The 
alveolar sarcomata, for example, consist of groups of cells en- 
closed in the meshes of a fibrous network. These names are, 
however, more descriptive than indicative of essentially distinct 
kinds of tumor, and the demarcation between the different varie- 
eties is not a sharp one. Many sarcomata consist of cells of 
various shapes, either in different parts or intermingled throughout 
the growth. This necsssitates the insertion of mixed varieties be- 
tween the above groups of distinct and relatively pure types. Fur- 
thermore, the cells not only differ in shape, but also in size, so that 
a distinction may be made between the small round-cell sarcom- 
ata and the large round-cell variety ; but notwithstanding the 
fact that this grouping is somewhat artificial, it has a certain clinical 
value, because it indicates in a rough way the degree of differ- 
entiation attained by the tumor, and for this reason it will be well 
to adhere to this classification and to consider the purer types sepa- 
rately, bearing in mind that the mixed forms of sarcoma possess 
characters intermediate between those of the simpler forms upon 
which the classification is primarily based. 



a. Sir ALL Round-cell Sarcoma, — This variety presents the 
least degree of structural differentiation. The substance of the tumor 
is composed of small, round cells with single vesicular nuclei enclosed 
in very little cytoplasm. They are so closely aggregated that 
they appear to be in contact; but careful examination will often 

reveal a small amount of a nearly 
homogeneous, finely granular, or 
slightly fibrillated intercellular 
substance (Figs. 324 and 325). 
The tumor is supplied with blood- 
vessels having very thin walls. 

Fig. 325. 

Small round-cell sarcoma of the neck. 

Fig. 324.— Section only moderately magnified, showing the extremely cellular character of 
the growth ; the great friability of the tissue is owing to the minimal amount of inter- 
cellular substance it contains and the intimate relations between the tissue of the tumor 
and the walls of relatively large, thin-walled bloodvessels. 

Fig. 325. — Sketch of a fragment of the tumor, more highly magnified. The cytoplasm around 
the nuclei is hardly distinguishable, and the cells are separated by only a small amount 
of an indefinite intercellular substance. 

formed of a single layer of cells, which are usually more protoplasmic 
than those of fully developed endothelium. These vessels may be 
very abundant, but, especially if the tumor has been removed by 
operation, they are likely to be empty and their walls so collapsed 
that they are not easy of recognition. When seen in longitudinal sec- 
tion these emptied vessels appear as a double line of elongated, some- 
what fusiform cells, lying in close contact with the cells of the rest 
of the tumor. In cross-section they are still more difficult of detec- 
tion, since the swollen endothelial cells then look very much like 
the contiguous cells of the growth itself. 

Where the sarcoma is infiltrating the surrounding tissues groups 
of the round cells, distinguished from the leucocytes which may be 
present by the character of their nuclei, appear in the interstices of 
the tissue, the formed elements of which inidergo atrophy, either 
because subjected to increased pressure or because their nutrition 
is interfered with (Fig. 326). In this way the tumor increases the 

TUMORS. 363 

territory whioli it occupies, but the more central portions also^row. 
After a certain stage of growth has been attained the older portions 
of the tumor are liable to undergo degenerations or necrosis. 

It is evident, from the structure of this variety of sarcoma, that 
it must be very prone to suffer metastasis. This may take place 
through the lymphatics of the surrounding tissues, favored l)y the 
infiltrating qualities of the growth ; or it may take place through 
the bloodvessels, some of the cells finding their way through the 
thin walls of the vessels in the tumor itself, or into the luniina 
of larger vessels through an infiltration of their walls. In either 

Fig. 326. 


Small round-cell sarcoma of the pelvis, infiltrating dense fibrous tissue. 

of these ways a generalization of the growth may take place, sec- 
ondary nodules appearing in many parts of the body. 

Round-cell sarcomata of this type are liable to arise in the 
connective fibrous tissue between the muscles, in the fascia?, etc. 
They also find their origin in the skin, testis, and ovary. They 
are among the most malignant of the sarcomata, growing rapidly, 
infiltrating their surroundings, and undergoing metastasis. 

b. Lymphosarcoma. — This variety of sarcoma differs only 
slightly in structure from the small round-cell form in possessing 
a somewhat more elaborate stroma, a term which could hardly be 
applied to the small amount of intercellular substance found in the 
latter. In the lymphosarcomata the cells closely resemble those of the 
small round-cell variety of sarcoma, but they lie loosely aggregated 
in the meshes of a reticulum of fibres, many of which constitute the 
processes of stellate cells penetrating the substance of the growth 



and possibly joining each other This reticiihim is somewhat more 
pronounced around the bloodvessels which it supports. The cells 
may be shaken out of this reticulum, if unembedded sections are agi- 
tated with water (Fig. 327). 

Fig. 327. 


Sections from lymphosarcomata. (Kaufmann.) I, firmer variety, with a pronounced 
stroma; from a mediastinal tumor. II, softer variety, with a more delicate stroma; 
from a tumor of the small intestine, a, capillary bloodvessel. 

This structure closely resembles that of the lymphadenoid tissue 
found in the normal lymph-nodes, and there is danger of con- 
founding the growth with a simple or inflammatory hyperplasia of 
those organs. This danger is enhanced by the fact that these sar- 
comata frequently find their origin in a lymph-gland or the lymph- 
adenoid tissue in the mucous membranes. When the enlargement 
of the gland is the result of hyperplasia the superabundant tissue 
is confined within the capsule of the gland, which enlarges as its 
contents increase in amount. There is also a history of some 
inflammatory process within the lymijhatic province to which the 
gland belongs. Such is not the case when the increase of tissue is 
due to the development of a tumor. The growth usually pierces 
the capsule of the gland, and cannot be traced to inflammatory 
causes. This penetration of the capsule is an evidence of the in- 
filtrating power of the growth. Like the small round-cell sar- 
coma, this variety is lialjle to early and extensive metastases, and 
is hardly less malignant than that form. 

c. Laege Round-cell Sarcoma. — As the title implies, this 
tumor is composed of larger cells than found in the small 
round-cell sarcomata. The greater size is due to a larger amount 
of cytoplasm, in which are rather large round or oval vesicular 
nuclei, usually one in each cell, but not infrequently cells with two 

TUMORS. 365 

or even more niu'lci are observed. The intercellular substance is 
more abundant and more distinctly tibrillated than is the case in 
the small round-cell sarcomata, but it is not uniformly distributed 
between the individual cells. These are usnallv airtrrcirated in 
grou[)s, which are surrounded by the denser bantls of fibrous tissue. 
From these, little fibrous twigs may sometimes be seen penetrating 
between the individual cells of the group. This arrangement gives 
sections of the growth an alveolar appearance (Fig. 328). The 

Large round-cell sarcoma of the toiij^uo: a, large round cell containing three nuclei; h, 
delicate tibrous stroma supporting the cells of the growth. At the point 6 this stroma 
contains a collapsed capillary bloodvessel. The large round cells are probably of endo- 
thelial origin. The growth occurred in a man aged sixty-one years, and in the course of 
eight months had attained the size of a hickory-nut. " 

fibrous tissue itself may be highly developed, resembling the adult 
form ; or it may be more highly cellular and contain large spindle- 
.shaped cells. When this is the case the tumor becomes a mixed- 
cell sarcoma composed of large cells, partly round, partly fusiform. 

The large round-cell sarcomata spring from the .same tissues 
that give to the small round-cell sarcomata, but it is probable 
that they owe their production in large measure to a proliferation 
of the endothelial cells of those tissues, and are, therefore, etiologi- 
cally related to the endotheliomata. They grow less rapidly than 
the small round-cell and lympho-sarcomata, and, as would be ex- 
pected from a study of their structure, they are less prone to 
infiltrate their surroundings or to be subject to metastasis. They 
are, to a corresponding degree, less malignant in their clinical mani- 

(/. Spixdle-cei.l Sarcomata. — The shape of the cells of this 
group of tumors betokens a higher state of differentiation than is 
found in the small round-cell sarcomata, the cells having more 



nearly approached the character of those found in the adult fibrous 
tissues ; but although in this respect all the tumors of this group 
are more nearly like the normal tissues, they differ greatly among 
themselves in regard to the extent to which the formative activities 
of their cells are displayed in the production of intercellular sub- 
stances. Some possess hardly more intercellular substance than the 
small round-cell varieties, while others have the appearance of a 
rather highly cellular fibrous tissue, the intercellular substances 
beiuff abundant. 

The fusiform cells of the tumor possess oval vesicular nuclei, 
around which is an amount of cytoplasm varying in the different 
individual growths. Sometimes the cytoplasm is abundant, and 
the tumor appears composed of large spindle-shaped cells, tapering 
at their ends to form processes of various lengths (Fig. 329). In 

Fig 329. 

Large spindle-cell sarcoma. (Birch-Hirschfeld.) 

other cases the cells are small and the cytoplasm is reduced to a 
thin investment of the nucleus, at the ends of which it rapidly 
dwindles to a very thin fibrous process. The spindle-cell sarcomata 
may, therefore, be divided into large- and small-cell varieties. 

The cells are usually arranged with their long axes parallel to 
each other, forming bundles or broad bands of tissue, in which the 
cells all have the same general position. This direction is generally 
the same as that taken by the bloodvessels (Fig. 330). These have 
very thin walls, as in the preceding varieties of sarcoma, and the 
cells of the tumor appear to be in direct contact with the outside 

TUMORS. 367 

of the vessels. The cellular htindles may not all lie parallel to 
ea{;h other, but fVecjuently are iuteruovcn, so that a given section 
will contain longitmlinal, cross, and oblique sections of the indi- 
vidual cells. Such appearances must not be mistaken for the .some- 
what similar aspect of sections of mixed-cell sarcomata. 

The spindle-cell sarcomata are among the most common of tu- 
mors. They may arise from any of the connective tissues. When 
they spring from the periosteum they are apt to have an imper- 
fectly formed bony tissue associated with the structure of the sar- 

FiG. 330. 


Spindle-cell sarcoma. (Rindfleisch.) Where the cells of the tumor lie parallel to the 
plane of the section their spindle shape is manifest ; where they are perpendicular to 
the plane of the section their cross-sections appear round. The bloodvessels appear to 
have no proper walls, but to be bounded by the tissue of the neoplasm. 

coma. They then form osteosarcomata or osteoid .sarcomata, accord- 
ing to the perfection with which the structure of normal bone is 

In judging of the probable malignancy of a given specimen of 
spindle-cell sarcoma, the rapidity of its growth, as evidenced by 
the number of mitotic figures seen in the cells, and the abundance 
of fibrous intercellular substance, must be taken into consideration. 
As a group, the spindle-cell sarcomata are less malignant than 
the small round-cell sarcomata ; but this is because the majority 
of spindle-cell sarcomata have a well-marked intercellular sub- 
stance of fibrous character. Those forms which are almost desti- 
tute of this are hardly less malignant than the small round-cell 
variety (Figs. 331 and 332). 

e. GiAXT-CELL Sarcoma. — This form of sarcoma is charac- 
terized by the presence of large, multinucleated cells lying among 
the other cells of the growth. These giant-cells may be scattered 


Fig. 331. 


?i.i'7%''^ -^J 

Example of a highly malignant variety of spindle-cell sarcoma. Sarcoma of the uterus with 
oval nuclei, indicating somewhat spindle-shaped cells. In other respects the character 
of the tumor resembles that of a small round-cell sarcoma, a, contiguous fibrous tissue 
of the uterus ; 6, sarcomatous tissue ; c, bloodvessels, (v. Kahlden.) 

Fig. 832. 

Example of a highly malignant sjiindle-cell sarcoma. Spindle-cell sarcoma infiltrating the 
liver. I 2, liver-cells; s s z, spindle-cells of the sarcoma; c, endothelium of the intra- 
lobular capillaries. (Heukelom.) 



pretty nnifornily tlin)u<j;;h<)ut the jjrowtli, or they may be much 
more abundant in some places than in others. Tlie cells with single 
nuclei, among which the giant-cells are found, may be of the 
spindle-shaped variety, or they may be polymorphic, in which case 
cells of various shapes and sizes are met with. 

The giant-cell sarcomata are usually derived from the medulla 
of bone. They constitute the most common form of epulis (Fig. 
333), and frequently attain very large dimensions when they take 

Fig. 333. 

b ' 

Giant-cell sarcoma of the superior maxilla ; epulis : a, large giant-cell, with numerous 
nuclei ; b, tangential section of a similar cell. Aside from the giant-cells, the growth is 
composed of spindle-cells and a moderate amount of a fibrous intercellular substance. 
The tumor was removed from a man forty-one years of age, and was of slow growth, 
having attained the size of a filbert in two and a half years. 

their origin in the marrow of the larger bones, such as the femur 
or tibia. They are not, however, confined to bone, but may occur 
in other situations ; e. g., the breast. 

The malignancy of giant-cell sarcomata must be estimated in 
individual cases according to the principles already elucidated. 

/. Mp:lanosarcoma. — Sarcomata which spring from pigmented 
tissues, such as the choroid of the eye, pigmented moles, etc., fre- 
cpiently show a pigmentation of their constituent cells, the pigment 
appearing as brown granules of various size within the cytoplasm 
of the cells. The cells are not all equally affected, and many may 
be seen without any sign of pigmentation. The tumors are apt 
to be of the spindle-cell or large round-cell varieties, and are 



Fig. 334. 

Melanosarcoma of the skin. (Ribbert.) The growth is an alveolar large round-cell sarcoma, 
containing cells that have undergone a pigmentary degeneration. Some of these cells 
contain so much pigment that the cellular constituents are invisible. 

considered as rather more malignant than the non-pigmented forms 
of those tumors (Fig. 334). 


Muscular fibres of either the smooth involuntary or the striated 
variety may enter into the formation of tumors. Tumors made up 
of the former are called leiomyomata; those containing striated 
muscle, rhabdomyomata. 

1. Leiomyoma. — The cells of the tissue forming leiomyomata very 
closely resemble those of normal smooth muscular tissue, but tliey 
may show a greater variation in size. They are arranged in bundles, 
their long axes parallel to each other ; and these bundles are inter- 
woven in such a way that sections of the tumor contain longitudinal, 
oblique, and cross-sections of the individual fibres (Fig. 335). Between 
the bundles there is a variable amount of fibrous tissue, giving sup- 
port to the bloodvessels of the tumor. This fibrous tissue may be 
so abundant as to form a large element in the structure of the tumor, 
whicli is then denominated a fibrorayoma. It may, also, occasion- 
ally be imperfectly developed, converting the growth into a leio- 
myosarcoma. The muscular tissue may undergo a hyaline degen- 
eration and become the seat of calcareous infiltration, or the cells 
may be the seat of fatty degeneration with subsequent softening. 

Leiomyomata arise in parts wliich normally contain smooth mus- 



Fig. 335. 

Leiomyoma of the uterus. (Bircli-Hirschfeld.) 

oiilar tissue. They are common in the uterus, but may occur in the 

Fig. 336. 

Rhabdomyosarcoma of the kidney: a, o, a, imperfectly developed striated muscle-fibres; 6, 
tissue composed of small round and spindle-shaped cells, separated by considerable deli- 
cate fibrous intercellular substance. In other parts of the growth, which was the size 
of the fist, this tissue was more di.«tinctly sarcomatous and the amount of muscular tissue 
smaller. The child from which this tumor was removed was about two years old. 

intestinal walls, the urinary tract, or the skin. When pure, or when 
associated with fibrous tissue alone, they are benign. 



2. Rhabdomyoma. — The striated muscle-fibres of rhabdomyomata 
are often so imperfectly developed that they are difficult of recognition. 
They are much more attenuated than the normal fibres, and may be 
reduced to very narrow and tapering structures that possess only traces 
of striation. Staining with eosin will often aid their detection among 

Fig. 337. 

Isolated muscle-fibres from a rhabdomyoma of the oesophagus. (Wolfensberger.) a, b, 
appearances simulating a sarcolemma, probably due to adherent fragments of the inter- 
cellular substance. 

the fibres of the connective tissue surrounding them, as it stains the 
contractile substance a coppery-red. The nuclei of the muscle-cells 
are frequently numerous, and may occupy the centre of the fibre, 
the imperfectly formed contractile substance lying at the periphery. 
In some rare cases the tumor is composed almost exclusively of 



striated muscle-fibres, arranged in irregular, interwoven bands, with 
a little vascular fibrous tissue among them. In other cases the 
muscular fibres are sparsely distributed through the growth, and 
can often be found only after a prolonged search. In these cases 
the tissue iu wliich the muscle is situated is usually some variety of 
sarcoma, when the whole tumor is known as a rhabdomyosarcoma 
(Figs. e336, 337, and 338). Such mixed tumors are most frequently 
found in the genito-urinary tract, especially in the kidney, and may 
attain very large size. They are apt to occur in the early years of 

Fig. 338. 

Isolated ceUs from a rhabdoniyoma of the heart. (Ccsaris-Demel.) 

life, and are probably due to developmental anomalies. The sarcom- 
atous element, which is usually predominant, gives them a highly 
malignant character. 


Reference has already been made to the manner in which the 
bloodvessels of a part may proliferate under the influence of the 
inflammatory process, and also to the fiict that when tumors 
develop the bloodvessels proliferate in a similar way to form new 
vascular areas within the tumor, from which the latter derives its 
nourishment. These instances of proliferation may be regarded as 
the natural on the part of the vascular system to the de- 
mand thrown upon it by the formation of new tissues. In a general 
way, they are limited to the needs of the tissues which they supply. 
A vascular ]>roliferation may, however, take place irrespective of 


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. 



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 


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- 

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. 


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- 



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. 



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. 


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 

In examining sections of the brca.'^t witli a view to determining 



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. 




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. 


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. 


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 



a general tubular structure, the acini Ijcing in an undeveloped 

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. 


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. 


tively nine and fourteen months after functional activity had been 

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 



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. 


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 



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 



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. 



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 

Care must be taken not to confound 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 of the adenofibroma. The development of the fibrous ti.ssue in 



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 



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- 

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- 

Via. 358. 


'^^ .m^m>!k 




\: -.-^ 

^, '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; </. nucleus abnor- 
mally rich in chromatin preparatory to cell-division ; e, fat-globule in the epithelium of 
the tumor, showing a tendency to fatty degeneration. 


ment of the cells is often strikingly shown in secondary tumors of 
the lung, in which the cells have appropriated the pulmonary alveoli 
for their stroma. 

It occasionally happens that the connective tissue that forms the 
stroma of a carcinoma does not progress in its development to the 
formation of fibrous tissue, but assumes a sarcomatous character. 
Such tumors are called "carcinoma sarcomatosum." A more fre- 
quent association is one of carcinoma with adenoma, " adenocar- 
cinoma " (Fig. 358). In these neoplasms, either the two forms of 

Fig. 359. 

Epithelioma of the cheek. (Ernst.) a, flclicato tongues of epithelium extending into the 
lymphatics of the part; 6, c, larger masses of epithelium containing pearl-bodies. 

epithelial tumor may occupy different portions of the growth, or 
the general character of the growth may be that of a rather typical 
carcinoma — ?'. ^., a carcinoma showing indications of a development 
beyond the undifferentiated state analogous to an embryonic gland 
— or that of a rather atypical adenoma. 



3. Epithelioma. — 'I'liis tumor is essentially a carcinoma springing 
from stratified epithelium. Under normal circumstances the cells 
of this variety of" epithelium multiply in its deeper layers and are 
gradually pushed toward the surtUee while they mature. P]pithe- 
lioraata are produced when the proliferating cells penetrate the 
underlying tissues in columns, which ramify through those tissues 
and ultimately appear as the contents of well-defined alveoli sur- 
rounded by a fibrous-tissue stroma similar to that present in car- 
cinomata (Fig. 359). The epithelium retains its general characters : 
the cells at the periphery of the alveoli multiply, and either further 

Fig. 3G0. 

*aM — o 

Epithelial pearl-body from an epithelioma of the lip : a, pearl-body ; b, surrounding epithe- 
lium, forming one of the epitheliomatous tongues or columns; c, round-cell infiltra- 
tion of the contiguous fibrous tissue. 

infiltrate the surrounding tissues or crowd each other toward the 
centres of the alveoli as they increase in number and size. Here 
they eventually undergo keratoid transformation, just as they w'ould 
upon the surface of the normal epithelium ; only here they are 
crowded toward the centres of the alv(H)li, where the horny scales 
become imbricated to form globular masses, called epithelial " pearl- 
bodies" (Fig. 360). The epitheliomata may penetrate into the 
lymphatics and be subject to metastasis in a manner entirely com- 
parable to that already described above. They arc, therefore, 
malignant, though of slower growth than the medullary or simple 
carcinomata, at least during the early stages of their development. 
It should always be borne in mind, when considering the prog- 


iiosis in a case of carcinoma or epithelioma, that metastasis may- 
take place while the primary growth is still of very small size, 
even before attention has been called to the existence of a tumor. 
An examination of the peripheral portion of the growth will often 
throw considerable light upon the probability that this has occurred, 
bv revealing an extension of epithelial cells into the lymphatics of 
the surrounding tissues. Cases of speedy recurrence of such a 
growth after operation are really cases in which tissues that have 
thus been infiltrated have not been completely removed. 

Much has been written within late years advocating the theory 
of a parasitic causation of carcinomata and epitheliomata. The 
appearances which have led to this belief are probably due to 
degenerative or morbid processes within the epithelial cells of the 
tumor, and not to the presence of parasites ; but further study of 
this subject may show that parasites have the power of causing 
rejuvenescence of cells and an emancipation from the ordinary 
restraints that regulate their development. 

4. Cystoma. — Attention has been called to the cystic adenomata 
of the mamma. Similar cysts may occur in other regions through 
dilatation of cavities normally present in the tissues by some fluid, 
usually of a serous character. It is best to exclude cystic growths 
in which the cystic character is evidently a secondary feature of the 
tumor, or where a cyst arises from the retention of a secretion or is 
due to the accumulation of a fluid in a normal cavity, from the 
group of tumors that are essentially cystic. Thus, for example, 
simple hydrops folliculorum of the ovary should not be classed with 
the cystic tumors of that organ. 

The ovary is the favorite site for cystic tumors of new formation, 
which may contain only a single cavity (unilocular) or several cav- 
ities (multilocular). Histologically, they may be grouped in three 
divisions : 1, simple, in which the walls of the cyst are smooth and 
covered with epithelium ; 2, papillary, in which there are ingrowths 
from the walls of the cysts into their cavities, either simple or branch- 
ing (Fig. 3G1) ; and, 3, dermoid, which contain structures simulating 
th(! normal skin : hair, imperfectly developed teeth, or other highly 
differentiated tissues, such as bone, etc. In the first two forms the 
fluid in the cystic cavities may be serous, mucoid, or colloid; fre- 
(lucntly it is difFcront in the various cavities of the tumor. In der- 
moid cysts there is often a greasy substance, similar to the sebum 
of the skiu, derived from sebaceous glands in the cutaneous struct- 


Fig. 301. 



Section from a papillary cystoma of the ovary. (Birch-IIirsclifcld.) Part of the wall sepa- 
rating two cystic cavities is represented. From this wall, papillary ingrowths arise, 
which project into the cavity of tlie cyst. They are comymsed of a delicate areolar tissue 
covered with columnar epithelium similar to that lining the cysts. 

ures of the growth. Similar dermoid cysts occasionally develop 
from the skin, but are usually lined with merely an epidermis, the 

Fig. 362. 


Gilomata of the brain. (Stroebe.) Composed of glia-cells of small type, with fine 




scales from which accumulate in the cavity of the tumor, where 
they may be mixed with sebum (wens). 

5. Grlioma. — The neuroglia, originally of epithelial origin from 

Fig. 363. 

Gliomata of the brain. (Stroebe.) Mixed type, containing cells like those in Fig. 362, but 
also large branching cells simulating ganglion-cells, "glioma gangliocellulare." 

In sections of gliomata stained by the methods in more general use the delicate processes are 
often not visible, but the nuclei are prominent. The tumor, therefore, appears highly 
cellular with a finely granular material (the unstained processes) between the cells. 

the ectoderm, may proliferate to form tumors, called gliomata. 
These diifer in their structure according to the variations in type 
presented by the glia-cells composing them (Figs. 362 and 363). 


Before leaving the subject of tumors it will be necessary to 
devote a few words to the consideration of growths that cannot be 
considered as primarily arising from either epithelium or connective 
tissues. The papillomata arc exam])les of such growths. These 
are over-developments of papillary structures normally present, or 
spring from mucous surfaces where such structures are normally 
either not present or are but poorly developed. 

TUMORS. 395 

A {xii)illoniu consists of vascularized fibrous or areolar tissue 
springing from a surface which is covered with epithelium. The 
denser forms which occur — e.(/., upon the skin — constitute "warts" ; 
but much more delicate papilloniata may spring from mucous mem- 
branes, such as that of the bladder, and are then known as villous 
tumors or villous papilloniata. In many cases the denser forms of 
papilloma appear to be hypcrtrojjliics due to irritation. But papil- 
loniata which seem to be true ne()j)lasms or tumors in the restricted 
sense of that term hitherto employed appear to be among the possi- 
bilities of morbid development. 




In selecting a microscope the followiug considerations are of 
importance : 

The stand should be supported on three points and rest firmly on 
the table; have a rack-and-pinion coarse adjustment, and a fine 
adjustment free from all loss of motion. It is rarely used in an 
inclined position, and a jointed stand is unnecessary. A triple 
nose-piece, or revolver, is a great convenience, and an Abbe con- 
denser with iris-diaphragm is almost indispensable. 

Three objectives are needed : a Leitz No. 3 or No. 4, No. 7, and 
^th or yV^'^ ^^^ immersion, or their equivalents of other manu- 
facture, are suitable powers for general use. Two oculars. No. 2 
and No. 4, will answer. 

The microscope should be protected from direct sunlight and acid 
fumes, and be kept in a dry, moderately cool place. When not in 
use it should be covered or placed in its case, to protect it from 
dust. If the lenses become dirty, they may be wiped with a soft, 
clean cloth or Japanese paper, either dry or moistened with water, 
and followed by a dry cloth or paper. Balsam or cedar oil may be 
removed with a cloth or soft paper moistened with xylol, after whicli 
the parts should be carefully wiped dry. 

In making microchemical tests special care should be taken not 
to let the reagents come in contact with the objectives. 

Objects should always be examined in a liquid, unless there is 
some special reason for examining them in a dry state ; and should 
be covered with a cover-glass, unless a cursory inspection with a 
very low power is all that is required. 



In studying a specimen always use the lowest power that will 
reveal the structures it is desired to see ; and, in any event, use 
a low power first, to get a general idea of the topography of the 
specimen. In this way the portions for more minute study can be 
readily selected, with a great saving of time. 

The proper illumination of the specimen is just as important as 
careful focussing. If the Abbe condenser is in use, employ the 
plane surface of the mirror during the day ; either the plane or the 
concave surface when artificial light is used, selecting the surface 
which causes less glare. The iris-diaphragm should be kept ad- 
justed so as to give the best definition of the specimen under exam- 
ination when the latter is in focus. It will be found that when 
colorless objects are examined a small opening gives the clearest 
picture, while with colored objects a larger opening is preferable. 
A small diaphragm serves to bring out the "structure-picture" ; a 
large diaphragm, the " color-picture " (see p. 402). 

A bottle of oil of cedar-wood, having approximately the same 
refractive index as the glass from which the cover-glasses are made, 
is furnished with the immersion-objectives. When these are used 
a drop of this oil is placed on the cover, and the end of the objec- 
tive immersed in this drop. This arrangement permits the light to 
pass from the object to the bottom lens of the objective without sen- 
sible refraction, increasing the amount of light entering the objec- 
tive, the sharpness of definition, and the purity of the color-picture. 
When the lens has been used the oil should be removed with a soft 
cloth or Japanese paper. The oil on the cover may be wiped off at 
once, or it may be allowed to dry and then removed with a cloth 
moistened with xylol. 

Microscopical Measurements. — These may be made, with a fair 
degree of accuracy, by means of an eye-piece micrometer-scale. 
This is a ruled disc of glass that can be placed upon the diaphragm 
within the ocular, where its scale should be well defined when seen 
through the upper lens of the eye-piece. Special micrometer ocu- 
lars are made which permit of focussing the scale, but these are 
unnecessary if the diaphragms of the ordinary oculars are in the 
right places within the eye-piece tubes. The value of the divisions 
of the eye-piece micrometer-scale must be determined by comparing 
it with the scale of a micrometer-slide wliicli is placed upon the 
stage of the microscope. These scales usually consist of 1 mm. 
divided into hundredths, and the eye-piece scale will have dif- 


ferent values for ctuli comhiMation of louses used and for every 
variation in the length of the microscope-tube. The unit for micro- 
se(»j»leal nieasnrcnients is one-thousandtii of a millimeter, or one- 
millionth of a meter; it is called a "micrometer," and is desig- 
nated by the Greek letter fi. One division of the micrometer-slide 
mentioned above would, therefore, equal 10 [i. From these data it 
is possible to calculate the value of each division of the eye-piece 
micrometer-scale in terms of fi for each combination of lenses, the 
length of the microscope-tube being fixed. (Most Continental 
stands and many American stands have graduated tubes, and the 
objectives are constructed for a standard tube-length of 160 milli- 

It is well for the student to get into the habit of estimating the 
sizes of the objects he examines. A good standard for mental com- 
parison is the diameter of the unaltered red blood -corpuscle, which 
is about 7.5 tJt. 


Useful preparations for study under the microscope may be pre- 
pared from tissues in one of three ways : 1, simple scrapings of the 
tissues may be mounted on a slide in the fluids derived from the 
tissues themselves, or in a neutral solution — e.g., 0.75 per cent, salt 
solution ; 2, the tissue-elements, cells, and intercellular fibres, etc., 
may be separated from each other by treatment with some macerat- 
ing-fluid — e. g., very weak chromic acid (1 : 10,000), 36 per cent, 
caustic potash, i alcohol ; 3, sections of the tissue may be prepared 
either while they are fresh, with a razor or a freezing-microtome, or 
after hardening. 

The first method has a limited application. It is serviceable 
only when the tissue-elements are so loosely held together that they 
readily separate from each other and can be examined in an isolated 
condition. This is the case with a considerable number of tumors, 
the superficial tissues of mucous nienibranes, the spleen, etc. If 
the inside of the cheek be scrajK'd with the finger-nail, and the 
material thus removed be diluted with saliva, placed upon a slide, 
and covered with a cover-glass, the squamous epithelial cells lining 
the cavity of the mouth will be readily seen in an isolated state. 
An appropriate dye may now be introduced under the cover, and by 
its means the nuclei of the cells stained, thus bringino: them into 
clearer view. 


When a simple scraping of the natural or freshly cut surface does 
not yield useful preparations, showing isolated tissue-elements, some 
process of maceration may be employed. Bits of the tissue are 
soaked for a time in some solution that serves to soften the cement- 
substances lying between the elements of the tissues, so that they 
may be easily separated with needles (teasing). Such specimens 
are usually best examined when mounted on a slide in some of the 
macerating-fluid. Many of the macerating-solutions not only favor 
the separation of the constituents of tissues, but also preserve them, 
so that a fair idea of their natural size and shape may be obtained 
from such preparations. It is evident, however, that with this 
method very little can be learned of their arrangement in the tis- 
sues before they were separated, and a knowledge of that arrange- 
ment is often of greater importance in the de'termination of the 
character of the tissue than a knowledge of the exact shape and 
size of the tissue-elements. 

The third method, that of preparing sections of the tissues, is the 
one most commonly employed, because it yields the most useful 
results. The structural elements composing the tissues are seen in 
their natural relative positions, and can be distinguished from each 
other and identified by the use of dyes and other reagents that 
affect them in some characteristic manner. But in order to ob- 
tain useful sections the tissues must almost always undergo some 
preliminary treatment with reagents, to give them a proper consist- 
ency for cutting and to hold the tissue-elements together so that 
the sections shall not fall apart after they have been cut. This may 
be accomplished by freezing the tissue before cutting it ; but more 
satisfactory results are obtained by causing a coagulation of the 
albuminous substances and subsequently extracting some or all of 
the water contained in the tissues. These changes in the tissues 
give them a firmness which favors the prejiaration of very thin sec- 
tions ; but sometiraies even they are inadequate, and then the tissues 
are usually impregnated with some substance, like paraffin or col- 
lodion, which fills the interstices of the tissues and can then be 
hardened, when it serves to hold the tissue-elements together and 
retain them in their natural positions. The paraffin or hardened 
collodion is cut WMth the tissues and keeps the sections from disinte- 
grating. Before mounting the section, the substance used for im- 
pregnation may be removed from the section, or it may be retained 


l)criiuinently, since it is usually easily recognized in the specimen 
and does not interfere with its study under the microscope. 

Tiie study of tissues by means of sections has the disadvantage 
that the elements of the tissues are cut, and tlie sections contain the 
resulting portions as well as complete elements. The incomplete 
portions lie near and at the surfaces of the sections, where they are 
in clearest view, while the uncut elements are situated in the body 
of the section, more or less obscured by the overlying portions that 
have been cut by the knife. Moreover, the tissue-elements may lie 
obli(|Uely to the })lane of the section, so that only a portion of them 
can be seen at a time, the rest being brought into clear view only 
when the focal plane is raised or lowered. These circumstances and 
the fact that the tissue-elements are frequently closely crowded 
together make the* interpretation of sections a matter of some dif- 
ficulty in many cases. These difficulties are in a measure overcome 
by examining sections of different thicknesses, but a more satis- 
factory Avay of studying the structure of a tissue is to examine por- 
tions after maceration as well as in section. 

The processes of coagulation and dehydration, which have already 
been mentioned as usual preliminaries to the cutting of sections, 
deserve a few words in explanation of their purposes. 

The coagulation of the albuminous substances in the tissues has 
for its chief aim the preservation of the minute structure of the 
tissue-elements, so that a lapse of time or the subsequent manipula- 
tions of the tissues shall not cause an alteration in the details which 
it is desired to study. If this precaution be omitted, the tissues 
nndergo post-mortem changes which scriouslv alter the appear- 
ance of the elements of M^hich they are composed. Coagulation 
brought about for this purpose is called " fixation " of the tissues. 
It may be induced in a variety of ways : the tissues mav be sub- 
jected to heat for a few moments, thus rendering the albumins they 
contain both solid and insoluble ; but the more usual procedure is 
to immerse the tissues in a solution of some substance that causes 
rapid death with coagulation. These solutions are called fixing- 
solutions, and not infrequently the substances they contain not only 
cause death and coagulation, but also form a union Nvith some of 
the structural materials of the tissues which may facilitate their 
subsequent recognition. 

The number of formulae that have been devised for the prepara- 
tion of fixing-solutions is very great, and some of the solutions are 



better for the fixation of some tissues than for others. As a rule, 
those sohitions that most perfectly preserve the finer intracellular 
details of structure have very little power of penetrating masses 
of tissue. They can, therefore, only be employed when very small 
bits of tissue are to be fixed. Other fixing-solutions penetrate 
much better, but fail to fix the most delicate structures, which may 
undergo changes before they are preserved. It follows that the 
choice of the method of fixation must in each case depend upon 
the object to be attained. 

The removal of water from the fixed tissues is accomplished by 
means of alcohol. The fixing-agents are nearly all aqueous solu- 
tions, and while they increase the consistency of the tissues to a 
certain extent, they do not usually render them sufficiently firm for 
the preparation of thin and uniform sections. If the Avater in the 
tissues be replaced by alcohol, a greater and more uniform con- 
sistency is obtained, and the tissues are also partly prepared for 
impregnation with an embedding-material (collodion or paraffin) 
should that be necessary for section-cutting. 

After sections of fixed tissues have been obtained they usually 
require staining before they can be profitably studied. The chief 
reason for this will appear in the following explanation : 

When a specimen is examined under the microscope differences 
in structure among the colorless elements of the specimen may be 
seen, or differences in color between the different elements may be 
perceptible. We may, then, distinguish between a " structure- 
picture," due to differences that are not those of color, and a " color- 
picture," due solely to such differences. The manner in which the 
latter is produced is, perhaps, self-evident. The structure-picture 
is the result mainly of differences in refraction due to the various 
densities of different parts of the specimen. But the processes of 
fixation and hardening have for their purpose the rendering of the 
tissues of a relatively uniform density. They must, in consequence, 
tend to obliterate the details of the structure-picture which the 
sections yiekl wiien viewed under t])e microscope. For this reason 
the sections are stained, which converts the structure-picture into a 

The substances composing the tissues have various affinities for 
dyes, and it is possible to take advantage of this in staining sec- 
tions, so that structures of the same nature shall receive one color, 
wliile those of different composition shall be dyed of a different 


hue or an entirely (Utlerent color. Tlie coloriiig-inatters, when so 
eniph)yecl, not only bring ont the structure of the tissue by creating 
a color-picture, but they also serve as valuable reagents in revealing 
the nature of the substances to which they impart a color. Again, 
it is often ?iecessary that a certain method of fixation or other pre- 
liminary treatment should be used before the particular dye selected 
can display its greatest selective power for a particular substance. 
These facts exj)lain the great number of formuUe for stains and the 
preparation of specimens that are found in tht; technical text-books 
and journals. The subject has become so expanded within recent 
years that it has almost created a distinct branch of learning ; but 
it will only I)e necessary for the student of medicine to acquire a 
knowledge of a few methods that will serve to reveal the general 
structure of cells and the characters of the intercellular substances. 
The general outline of the procedures in common use for this pur- 
pose are as follows: 1, fixation; 2, hardening; 3, impregnation; 
4, embedding ; 5, cutting ; 6, staining ; 7, dehydration ; 8, clearing ; 
9, mounting. 

Some methods of preparation combine one or more of these steps 
in a single manipulation, thus considerably reducing the time requi- 
site for the completion of the process. Other methods necessitate 
the intercalation of still other manipulations, or the subdivision 
of those already enumerated. 

Methods of Fixation, 
1. Miiller's Fluid. — This classic fixing- and hardening-solution con- 
sists of potassium bichromate, 2.5 per cent., and sodium sulphate, 
1 per cent., dissolved in water (preferably distilled water). It is 
slow in action, requiring from six to eight weeks for the preservation 
of an average specimen, but with proper care can be made to yield 
excellent results when the finer details of structure are not to be 
studied. It is important to use large quantities of the fluid, at 
least ten times the volume of the tissues immersed in it, and to 
renew the fluid so frequently that its strength shall be constantly 
maintained. When fresh tissues are placed in Miiller's fluid they 
speedily render it cloudy. This is a sign that the fluid should be 
renewed, even if only an hour has elapsed since the tissues were 
placed in it. When cloudiness no longer appears the fluid should 
be renewed once a day for the first two weeks : after that, two or 
three times a week till the process is completed. 


After fixation in Miiller's fluid specimens should be washed in 
running water over night, or for twenty-four hours, and then hard- 
ened in alcohols of progressively greater strengths. While in the 
weaker alcohols specimens should be kept in the dark, to avoid 
the formation of precipitates, which occur under the influence of 
light. Pieces of tissue placed in Miiller's fluid should not be more 
than 1 cm. in thickness. 

Two excellent modifications of Miiller's fluid have been devised 
by Zenker and Orth for the purpose of hastening the fixation and 
of securing a more faithful preservation of structural detail. 

2. Zenker's Fluid. — 

Potassium bichromate, 2.5 grams. 

Sodium sulphate, 1 gram. 

Mercuric chloride, 5 grams. 

Distilled water, 100 cc. 

To this stock solution 5 per cent, of glacial acetic acid is to be 
added just before use of the fluid. 

Zenker's fluid fixes tissues in from three to twenty-four hours. 
The pieces should not be more than 5 mm. thick, and after fixa- 
tion should be washed for several hours in running water and then 
hardened in alcohol. 

This solution possesses the disadvantage that a precipitation of 
mercury or some mercurial compound is likely to take place within 
the tissues. This deposit may be, at least in great measure, removed 
from the tissues by adding a little tincture of iodine to the harden- 
ing-alcohols. The iodine combines with the mercury and produces 
a soluble compound, which is dissolved out by the alcohol. As the 
iodine disappears from the alcohol the latter becomes bleached, and 
frosli tincture must be added until the alcohol remains permanently 
tinged. If, after sections of the tissue have been prepared, they 
are found to contain a mercurial deposit, this can be removed by 
treatment with dilute iodine tincture or with Lugol's solution. 

3. Orth's Fluid.— 

Potassium bichromate, 2.5 grams. 

Soditmi sulphate, 1 gram. 

Distilled water, 100 cc. 

This stock solution is Miiller's fluid. Before use, 10 cc. of for- 


nialdeliyilc (40 per cent.) is to be added to every 100 cc. of the 
Midler's H.iid. 

Orth's rtuid fixes in three or four days. The pieces of tissue 
should not be more than 1 em. thick. Tiie time for fixation can 
be shortened if smaller pieces are used and the process is carried 
on at a slightly elevated temperature ; e. g., in an incubator kept at 
37° C. (98.6° F.). After fixation the specimens should be washed 
in runnino; water, as in the previous methods. 

4. Mercuric Chloride Solution. — A saturated solution of corrosive 
sublimate in 0.5 per cent, salt solution is prepared by heating an 
excess of sublimate crystals in the salt solution and allowing the 
mixture to cool. The clear fluid is decanted from the crystals when 
desired for use. The penetration and action of the solution are 
favored by the addition of 5 per cent, of glacial acetic acid at the 
time of using. The thickness of the pieces of tissue should not 
exceed 5 ram., and much thinner pieces are better. Fixation takes 
place within six hours, after which the tissues may be washed in 
running water, or placed at once in 70 per cent, alcohol. If acetic 
acid has been used, it is best to w^ash in water before immersing in 
alcohol. Tincture of iodine should be added to the alcohol for the 
reasons given in the description of Zenker's fluid. 

5. Formaldehyde. — This gas is capable of being absorbed by 
water to form a 40 per cent, solution, but its volatility renders such 
a solution liable to deterioration. The strength employed for fixa- 
tion is usually 4 per cent., and may be prepared by adding 10 cc. 
of 40 per cent, formaldehyde to 90 cc. of distilled water. A 0.75 
per cent, solution of common salt may be substituted for the distilled 
water with possible advantage. 

Formaldehyde penetrates deeply and quickly into the tissues, 
which may be 1 cm. in thickness, and accomplishes fixation within 
twenty-four hours, but the preservation of structural detail is not 
very perfect. The solution is useful where the general characters 
of the tissues are to be determined and the details of the cells are 
of comparatively little consequence. After fixation the tissues may 
be washed in water, or placed directly in 70 per cent, alcohol ; or 
frozen sections may be at once prepared. Satisfactory sections may 
be obtained from small pieces of tissue if they are put in the for- 
maldehyde solution for an hour or two and then cut with the 
freezing-microtome. After they have been washed for a short time 
in water they may be stained by any of the more usual methods. 


6. Flemming's Solution. — This is a solution containing osraic acid, 
chromic acid, and acetic acid. It does not keep well, and it is best 
to prepare it just before it is to be used. For this purpose the 
following stock solutions may be kept on hand : 

A. 2 per cent, solution of osraic acid in 1 per cent, chromic acid. 

B. 1 per cent, solution of chromic acid in distilled water. 
Osmic acid is sold in sealed tubes containing 1 gram. To prepare 

the stock solution " A," the tube should be washed on the outside 
and a deep file-scratch made near its centre. It should then be 
broken into a bottle containing 50 cc. of a 1 per cent, solution of 
chromic acid in distilled water. The halves of the tube should be 
dropped into the bottle and its contents shaken at intervals until 
solution is effected. This solution had best be kept in the dark 
to avoid decomposition of the osmic acid. When required for use, 
prepare the Flemming's solution by mixing : 

Solution " A," 4 cc. 

Solution "B," 15 " 

Glacial acetic acid, 1 " 

Flemming's solution is especially useful for fixing the finer details 
of structure within the cell. It was devised for the preservation 
of the mitotic figures formed during karyokinesis, but its range of 
usefulness far exceeds that limited application. Its power of pene- 
tration is very slight and the pieces of tissue selected for fixation 
must be small. They should not exceed 2 mm. in their least 
measurement, and thinner pieces are apt to give better results. 
Owing to the presence of osmic acid, Flemming's solution stains 
fat a dark-brown or black color, and may be used as a reagent for 
the identification of fatty substances. 

Tissues should be left in Flemming's solution for about twenty- 
four hours, though twice that length of time would cause little if 
any harm. They must then be thorougldy washed in running water 
for twenty-four hours or longer, and hardened in alcohol. Since 
Flemming's solution is usually employed for the study of the 
individual cells, it is desirable to prepare very thin sections of the 
tissues that have been hardened in it. For this purpose embedding 
in paraffin is the best method. 

The foregoing fixing solutions will meet most of the requirements 
of the practitioner of medicine, but it frequently happens that he 


would like to obtain speedy results iroiu a niieroseopieal examina- 
tion without running the risk of loss of material or of poor results. 
When this is the case he may use absolute alcohol as a fixing-agcnt, 
thus taking advantage also of its ability to harden tissues and fit 
them for rapid embedding in collodion. 

7. Absolute Alcohol. — If fresh tissues are placed in strong alcohol, 
say 95 i)er cent., they are hardened ; but during the process there 
is an opportunity for the allnuninous fluids in the tissues to esca})e 
to a certain extent, and for shrinkage to take place in consequence. 
If absolute alcohol be employed, it causes such rapid coagulation 
that this leaching of the tissues does not take place. It is neces- 
sary, however, that the alcohol should remain of nearly its original 
strength, otherwise the water in the tissues will dilute it sufficiently 
to destroy this coagulating action. 

An excellent means for maintaining the strength of the alcohol 
is to immerse in it a few lumps of quick-lime. Take a small 
jar that can be hermetically closed by a tightly fitting cover 
(a museum jar, holding six or eight ounces, will answer). Place 
the lime in the bottom and then nearly fill with absolute alcohol. 
A few pieces of crumpled filter-paper are placed upon the lime and 
covered with a smooth piece placed so as to slant a little. The 
latter should lie near the surface of the alcohol, but be entirely sub- 
merged. Small pieces of the tissue to be fixed are placed upon the 
filter-paper where they will be covered by the alcohol. The alco- 
hol immediately coagulates the albuminous substances on the sur- 
face of the pieces and then gradually replaces the water in the 
specimen, coagulating the deeper-seated albumins as it penetrates 
the mass. The expelled water sinks to the bottom of the jar, owing 
to its greater specific gravity, and is at once taken up by the lime. 
It is essential for the success of this method that the lime should 
be exceedingly quick. It must show immediate signs of slaking 
if even a drop of water be placed upon it.^ 

It will be seen that this method not only fixes the tissues, but 
quickly dehydrates them. The real dehyd rating-agent is, however, 
the lime, the alcohol serving merely as a vehicle for conveying the 
water from the specimen to the lime. If the pieces of tissue are 

' A jar of absolute alcohol, prepared as above, may be used for purposes of fix- 
ing or hardening until the lime has become slaked or the alcohol so impregnated 
with dissolved fat that the latter interferes with embedding in collodion. When the 
latter is the case the hardened collodion is opaque or opalescent. 


small, not over 5 mm. thick, they will be hardened by remaining 
in the absolute alcohol over night, and mounted sections may be 
ready for examination by the next afternoon. 

8. Fixation by Boiling. — Throw small pieces of the tissue, not 
larger than 1 cm., into boiling 0.75 per cent, salt solution. Keep 
them at the temperature of boiling for two minutes. Then throw 
them into cold water. They may then be cut with the freezing- 
microtome, or may be placed in 70 per cent, alcohol for hardening. 
This method is excellent for the detection of albuminous exudates 
wdthin the tissues, but it causes so much shrinkage that it is not 
useful for general purposes. 

Methods of Hardening. 

Solutions of chromates, as Miiller's fluid, will, after a time, con- 
fer a pretty firm consistency upon tissues, and even render them 
brittle. Tissues fixed in corrosive sublimate are also very much 
hardened. But the usual practice is to harden specimens in alcohol 
after fixation. To obtain the best results this hardening should be 
done gradually, since immersion in strong alcohol is apt to produce 
undesirable shrinkage, affecting the various tissue-elements in dif- 
ferent degree. 

Seventy per cent, alcohol (736 cc. 95 per cent, alcohol to 264 cc. 
water) is weak enough to begin with. After the tissues have been in 
alcohol of that strength for twenty-four to forty-eight hours, accord- 
ing to the size of the pieces, they are placed in 80 per cent, alcohol 
(842 cc. 95 per cent, alcohol to 158 cc. water) for an equal length 
of time, and then in 95 per cent, alcohol. From the 95 per cent, 
alcohol thev are placed in absolute alcohol, if it be desired to embed 
them in either collodion or paraffin. If they are not intended for 
immediate use, they may be kept indefinitely in 80 per cent, alcohol. 

During the hardening it is best not to allow the tissues to rest 
on the bottom of the vessel containing the alcohol, as they are 
liable to slight maceration in the alcohol, which there becomes 
diluted with water from the specimen. They can be kept off 
the bottom by means of a little crumpled filter-paper. Specimens 
that have been fixed in a chromate solution should be kept in the 
dark while being hardened; those that have been fixed in corrosive 
sublimate should be hardened in alcohols to which a little tincture of 
iodine (sufficient to give tliem a sherry color) has been added. When 
absolute alcohol is used, its strength should be maintained by con- 


tact with <|iiick-lime (sec directions tor tixiiiir tissues in uljsolute 


Methods of Impregnation. 

When tissues arc so poRjus or iVialWe that sections are likely to 
tear or disintegrate it is desirable to impregnate them with some 
erabedding-material. The most useful substances for this purpose 
are collodion, or eelloidin, and paraffin. Whichever of these is 
used, it is necessary to remove the water from the specimen before 
the impregnation can be accomplished, for both collodion and 
paraffin are insoluble in water. Tissues that have been hardened 
in alcohol are to a certain extent already dehydrated. The residual 
water may be removed or reduced to a trace by treatment with 
absolute alcohol, in which collodion is soluble. 

The *' eelloidin " manufactured by Schering is an excellent prep- 
aration of gun-cotton, but almost equally good results may be 
obtained by using the more economical soluble cottons employed by 
photogra])hers. Two solutions in a mixture of equal volumes of 
ether and absolute alcohol (both, if possible, of Squibb's prepara- 
tion) should be kept in stock : one, a weaker solution, having about 
the consistency of thin mucilage; the other, a stronger solution, 
resembling a syrup. 

Collodion is soluble in absolute alcohol, so that tissues containing 
only that fluid are ready for impregnation without further prelim- 
inary treatment. When thorough impregnation is desired the tissues 
should be immersed in equal parts of ether and absolute alcohol for 
a few days, and then in the weaker solution of eelloidin or collodion 
for a number of days or weeks — the longer the better;^ but such 
complete impregnation is often unnecessary, and soaking for a day 
or two will often suffice if the sections to be made need not be very 
thin. It is not possil)le, in any event, to make very thin sections 
from tissues embedded in collodion ; but sections of large area mav 
be ol)tained, which is often of greater importance. For very thin 
sections it is better to use paraffin for the embedding-material, 
although the resulting sections will have to be smaller. 

Paraffin is insoluble in alcohol of all strengths. It is therefore 
necessary to remove the absolute alcohol from the tissues before 
they can be impregnated with paraffin. This may be done by 
immersing the tissues in some liquid that is a solvent for paraffin 

^ Impregnation may be greatly hastened if done at the body-temperature in a 
hermetically closed vessel. 


and is also miscible with alcohol. For this purpose, xylol, chloro- 
form, or oil of cedar-wood may be used. Xylol yields the most 
rapid results, but its use is contraindicated when it is desired to 
retain fatty substances that have been colored with osmic acid, as 
the xylol extracts them. If their preservation within the tissues 
is important, chloroform should be used ; but the sojourn even in 
that liquid should be as short as possible. Oil of cedar-wood prob- 
ably causes less change in tissues than chloroform, but the method 
is more protracted, and, requiring longer treatment in the paraffin- 
oven, probably has little ultimate advantage over chloroform for 
general purposes. 

If xylol is used, the tissues are transferred from the absolute 
alcohol to xylol, on which they at first float. Subsequently they 
sink, and are gradually rendered transparent as the alcohol is 
expelled by the xylol. When there are no opacities left the speci- 
men is ready for the paraffin-oven. These changes take from two 
to twenty-four hours. 

The treatment with chloroform is similar to that with xylol, but 
after the tissues have been cleared in chloroform (six to twenty-four 
hours) they are immersed in a saturated solution of paraffin in 
chloroform for about the same length of time. They are then ready 
for the paraffin-oven. 

When oil of cedar-wood is used the pieces should be soaked in 
two successive portions of the oil, about twelve hours in each, to 
insure removal of the alcohol. 

The foregoing steps are all preliminary to the actual impregnation 
with paraffin. 

It is important that the paraffin used for impregnation and 
embedding should have a wax-like, and not a crystalline, texture, 
and tliat its melting-point should be such that its consistency will 
be favorahlc for cutting at the average tcanperature of the labora- 
tory. Griibler, of Leipzig, furnishes excellent qualities of paraffin. 
For a room -temperature of 20° C (68° Fall.) a variety melting at 
50° C. (122° Fall.) will give good results. If the laboratory is 
warmer, a paraffin of higlier melting-point should be used. 

Impregnation is aceomplislied liy placing the bits of tissue in a 
bath of melted paraffin maintained at a temperature only slightly 
above that of fusion, say 52° C. (125.6° Fall.), if the paraffin melts 
at 50° C. (122° Fah.). This may be accomplished in a water- 
jacketed oven provided with a thermoregulator, or upon a plate of 


brass or copper, resting on a tripod and heated at one end by a 
burner. Wiion the latter method is employed the paraffin is melted 
in a little jjlass dish, whieh is moved along the i)late until a point 
is found at which the paraffin remains melted at the bottom, but is 
covered at the edges of the surface with a thin layer of congealed 

The length of time that the specimens should remain in the 
melted paraffin will vary with the character of the tissues and the 
method of getting rid of the alcohol which has been employed. It 
should not be protracted longer than necessary for complete impreg- 
nation, as heat is injurious to the tissues. When xylol has been 
used two hours will usually suffice if the pieces of tissue are small, 
and especially if they are transferred to a fresh paraffin-bath after 
about an hour. This renewal of the paraffin is still more important 
if oil of cedar-wood has been used. Chloroform requires a little 
more time than xylol, and should be transferred to fresh paraffin 
once or twice. 

When impregnation has taken place and the final bath of paraffin 
no longer has the slightest odor of the clearing-agent the pieces of 
tissue are removed from the bath with warmed forceps and placed 
on bits of writing-paper, to which they adhere. A designation 
of the specimen may be written on these papers, and the tissues 
kept in this condition until required for cutting. They must then 
be embedded. 

Methods of Embedding. 

The object of embedding is to surround the ])iece of tissue from 
which sections are to be cut with a mass of the embeddinjj-sub- 
stance, Avhich then not only supports the tissue when it comes in 
contact with the knife, but also affixes it to a block or other support 
which can be fitted into the clamp of the microtome. 

Microtomes designed for cutting paraffin usually have special 
supports for the embedded specimen, but blocks of hard wood may 
be used in their place. 

For the support of tissues embedded in collodion blocks of plate- 
glass are probably both better and cheaper than those made of other 
materials. They may be easily prepared from waste pieces of plate- 
glass, about a quarter of an inch thick, and " obscured " or ground on 
one surface. The glass may be cut into blocks of any desired size by 
scoring the smooth side with a diamond and then splitting the pieces 
apart with a sharp blow from a wedge-shaped hammer. The em- 


bedded specimen is affixed to the rough surface of these blocks by 
means of collodion, and the blocks may be numbered with a lead 
pencil upon the rough surface. The writing will be preserved from 
obliteration by the specimen subsequently placed upon it, and can 
be read through the glass. 

1. Embedding in Collodion (or Celloidin). — Tissues of firm con- 
sistency and moderately uniform structure, such as liver, kid- 
ney, and the majority of tumors which have been hardened, 
may be embedded without previous impregnation. Before this 
can be done, however, they must be either dehydrated with abso- 
lute alcohol, or soaked for a few hours in a mixture of equal 
volumes of ether and alcohol (95 per cent, alcohol will answer, 
if absolute alcohol is not to be had). For this rapid method the 
bottom of the piece of tissue must be flat and parallel to the plane of 
the desired sections. When the necessary trimming of the speci- 
men is completed moisten it with absolute alcohol or the ether- 
alcohol mixture, then dip it in the thick solution of gun-cotton and 
place it at once upon the ground surface of the glass block (pre- 
viously labelled). In a few minutes the collodion will have evap- 
orated sufficiently for the formation of a distinct pellicle upon its 
surface. When this has become firm enough to withstand gentle 
pressure immerse the block and specimen in several times their vol- 
ume of 80 per cent, alcohol. This will harden the collodion, and in 
the course of a few hours the specimen will be ready for cutting. 

Tissues impregnated with collodion had best be embedded by a 
slower process than the foregoing, although that method Avill answer 
where only a slight support of the tissue-elements within the speci- 
men is needed. A gradual concentration of the collodion within 
the tissues may be brought about in the following manner: 

Smear the inside of a small, straight-sided glass dish with a trace 
of glycerin and then fill it with enough moderately thick collodion 
to cover the pieces of tissue with a layer about one-quarter of an 
inch deep. Now place the specimens that have been in thin collo- 
dion in the dish, with the surfaces from which sections are to be cut 
resting on the bottom. Place the disli in a larger vessel with higher 
sides and loosely cover the latter. The ether and alcohol in the 
collodion will gradually evaporate, and their vapors will first fill the 
outer vessel and then overflow its sides. The depth of the outer 
vessel keeps tliese vapors in contact with the surface of the collo- 
dion, preventing the formation of a pellicle, which would retard 


<>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 

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 


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. 

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 


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 


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 



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- 










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 


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. 


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 


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 bein<r none too lonj^ for j^ood resnlt.s. 
If the staining be hastened by using a stronger solution, it suffers 
in sharpness. After staining, the sections are thoroughly washed 
in distilled water, and may then be subjected to a nuclear dye, such 
as hematoxylin. The proper acidulation of the diluted dye is of 
importance for the success of this method. If the solution is not 
sufficiently neutralized, the sections will not be stained ; if it is too 
acid, precipitation of the carmine will take place. 
3. Alum-carmine. — 


5 grams. 

Distilled water, 

100 cc. 

Carmine, " No. 40," 

2 grams. 

The alum is dissolved in the water with the aid of heat, the 
carmine then added, and the mixture kept at the boiling-point for 
about half an hour. It is then allowed to cool and filtered into the 
stock-bottle. Two or three drops of deliquesced carbolic acid may 
be added to prevent the development of fungi. 

Sections are stained in the undiluted, but filtered, dye for at least 
five minutes. There is no danger of over-staining. It is a pure 
nuclear stain, coloring the chromatin red. After staining, the sec- 
tions are either washed, and are then ready for dehydration, or 
they may receive a counterstain with picric acid, coloring the tissues 
a diffuse yellow. This may be most readily accomplished by adding 
a few small crystals of picric acid to the first dish of dehydrating 
alcohol (see p. 428). 

4. Borax-carmine. — 

Borax, 4 grams. 

Distilled water, 100 cc. 

Carmine, " No. 40," 3 grams. 

Alcohol, 70 per cent., 100 cc. 

The borax is dissolved in the water by warming, and the solution 
allowed to cool ; the carmine is then stirred in and the alcohol added. 
After standing twenty-four hours the solution is filtered into the 
stock -bottle, a process that is exceedingly slow. 


Borax-carmine is used for the staining of little masses of tissue 
before they are embedded. It is a nuclear dye, giving the chromatin 
a red color. It is useful when paraffin-embedding is to be employed 
and it is desirable to restrict the manipulation of the sections to a 

Small pieces of hardened tissues, not over 5 mm. thick, are trans- 
ferred from distilled water to the undiluted dye and allowed to stain 
for twenty-four hours, or longer. After staining they are immedi- 
ately placed in an acid alcohol, prepared by adding 5 drops of con- 
centrated hydrochloric acid to 100 cc. of 70 per cent, alcohol. The 
tissue should not rest on the bottom of the vessel containing the 
alcohol, but upon crumpled filter-paper, so that the extracted excess 
of coloring-matter may sink to the bottom. If the acid alcohol 
around the specimen becomes colored, fresh portions of alcohol 
should be used. The treatment with acid alcohol is continued until 
no more color is given off from the specimen. It is then transferred 
to 90 per cent, alcohol, in which it should remain for twenty- 
four hours, after which it can be subjected to the dehydration neces- 
sary for embedding. 

5. Orth's Lithio-carmine. — 

Carmine, " No. 40," 3 grams. 

Lithium carbonate, saturated aqueous solution, 100 cc. 

The solution of lithium carbonate is prepared by occasionally 
shaking: a mixture of distilled water and an excess of lithium car- 
bonate. Twenty-four hours will suffice for the production of a 
strong enough solution. The supernatant liquid is then filtered. 
Carmine readily dissolves in this solution. For preservation a 
crystal of thymol may be added. 

Lithio-carmine stains sections in about five minutes, and there is 
no danger of overstaining. Like borax-carmine, it requires after- 
treatment with acid alcohol. The sections should be transferred, 
without intermediate washing, to 70 per cent, alcohol containing 1 
per cent, of concentrated hydrochloric acid ; they may then be de- 
hydrated, and, if desired, counterstained Avith picric acid during the 

6. Unna's Methylene -blue. — 

Methylenc-l)lue, 1 gram. 

Potassium carbonate, 1 " 

Distilled water, 100 cc. 


W'licii required lur use, this solution slioukl be diluted with dis- 
tilled water to about one-tenth of its strength. It is a good stain for 
bacteria, and may also be used for staining the nuclei of tissues 
either by itself, or after using eosin as a diffuse stain. An aqueous 
solution of eosin, 5 per cent., is used for this purpose, the sections 
being stained for about five minutes. They are then washed to 
remove the excess of eosin, and stained in the diluted methylene- 
blue for about an hour. After this they are again washed and 
treated with absolute alcohol, whieii discharges the excess of blue. 
They are then cleared with xyl(»l and mounted in dammar or 
Canada balsam, dissolved in xylol. The preliminary staining with 
eosin may be omitted, when a contrast- or counterstain is not 

7. Aqueous Methylene-blue. — This is usually prepared at the time 
when needed by mixing one part of a saturated solution of the ani- 
lin-color in 95 per cent, alcohol with nine parts of distilled water. 
It is frequently employed as a general stain for bacteria. 

Other anilin-colors, such as fuchsin, gentian-violet, methyl-violet, 
and Bismarck-brown, may be kept in concentrated alcoholic solu- 
tion, to be diluted in a similar manner just before use. When these 
solutions are used for staining sections or cover-glass preparations 
the adherent dye is washed off wdth water, after which the intensity 
of the stain is reduced by the use of alcohol, 95 per cent, or abso- 
lute, which bleaches the portions of the specimen which retain the 
color with the least tenacity. If the action of the alcohol be main- 
tained for too long a time, the color may be discharged from all 
parts of the specimen. The method of overstaining a specimen, 
and then discharging the color from those parts where it is not de- 
sired, is a common one. The process of discharging the color is 
called the "differentiation" of the stain, because it serves to dis- 
tinguish those elements which hold the color strongly from those 
which part with it easily. 

8. Carbol-fuchsin. — 

Saturated alcoholic solution of fuchsin, 10 cc. 

Aqueous solution of carbolic acid crystals, 5 per cent., 90 cc. 

This solution should always be carefully filtered before use. 

9. Anilin-gentian-violet. — A. Ehrlich's formula : 

Saturated alcoholic solution of gentian- violet, 1.5 cc. 

Freshly prepared anilin-water, 8.5 cc. 


The anilin-water is prepared by shaking a few drops of anilin 
with distilled water, allowing the mixture to stand for about ten 
minutes, and then filtering through well-moistened filter-paper. 
The filtrate should contain no globules of the anilin. In order to 
avoid this the filtration should be stopped before all the watery 
part of the mixture has run through the paper, otherwise oily drops 
of anilin will follow. 

Precipitates are likely to occur in this gentian-violet solution 
when it is first prepared. After twenty-four hours these are less 
abundant. The solution deteriorates soon after that time, and 
should not be used more than a week after its preparation. 

B. Stirling's formula : 

Gentian-violet, 5 grams. 

Alcohol, 10 cc. 
Anilin, 2 cc. 

Distilled water, 88 cc. 

This solution keeps better than the preceding. Both must be 
filtered carefully through moistened filter-paper immediately before 
being used. 

10. Gram's Solution. — This is a differentiating agent used in con- 
nection with anilin-gentian-violet : 

Iodine, 1 gram. 

Potassium iodide, 2 grams. 

Distilled water, 300 cc. 

The specimens are first overstained with the gentian- violet solu- 
tion. They are then washed in water and placed in Gram's solution 
for from three to five minutes. While in this solution they turn a 
brown color, and the combination between the coloring-matter and 
some of the elements of the specimen is loosened. The specimen 
is then transferred to 95 per cent, alcohol, in which it remains until 
no more color is given off. If sufficient color has not been removed, 
the treatment with Gram's solution and alcohol may be repeated. 
After this differentiation the specimen may be dehydrated, cleared, 
and mounted ; or a contrast-stain may be used before those manipu- 
lations. This is a useful method for staining bacteria in sections 
of tissue when the species of bacteria are such as resist the decolor- 
izing action of the iodine. In this respect different species of bac- 


teriii clilfcr greatly, and the method is c(jiiim()nly em|)h)yed in Inic- 
teri()h)gieal work to distingnish those species which retain the stain, 
or are " positive to Gnun," from those which are decolorized or 
" negative to dram." 

11. Van Giesson's Picric Acid and Acid Fuchsin Stain. — 

A(pieous solution of acid fuchsin, 1 per cent., 5 cc. 

Saturated aqueous solution of picric acid, 100 " 

This solution serves to stain fibrous intercellular substances. It 
is used in the following manner : 

1. Slightly overstain with alum hiematoxylin ; c. g., Bohmer's 

2. Wash thoroughly in distilled water, 

3. Stain in Van Giesson's dye for five minutes. 

4. Wash in water. 

5. Dehydrate in 95 per cent, alcohol. 

6. Clear in oil of origanum. 

7. Mount in xylol-balsam or xylol-dammar. 

The tissues should have been fixed in a corrosive-sublimate solu- 
tion or one containing chromates ; e. (/., Miiller's fluid, Zenker's 
fluid, or sublimate solution. The connective-tissue fibres are stained 
red by the acid fuchsin. The reason for overstaining with htema- 
toxylin is that subsequent treatment with picric acid discharges 
some of that color. 

12. Benda's Iron-hsematoxylin Stain. — This is a powerful stain 
well adapted to the staining of paraffin-sections that have been 
affixed to cover-glasses. It stains nuclei and intercellular sub- 
stances, as well as the protoplasm of cells, various shades of gray, 
and the color is very permanent. The outline of the method is as 
follows : 

1. Mordant the sections (after affixing to cover-glasses, if that 
method is used) in a mixture of equal parts of liquor ferri sul- 
furici oxydati of the German Pharmacopoeia and distilled water for 
twenty-four hours. 

2. Rinse in distilled Avater, and then wash in three changes of 

3. Stain in aqueous solution of hoematoxylin, prepared by mix- 
ing 10 drops of a concentrated alcoholic solution of the crystals 
■with 10 cc. of distilled water. Stain for from one-half to twenty- 
four hours. 


4. Rinse in distilled water. 

5. Dififerentiate in equal parts of glacial acetic acid and distilled 

6. Wash thoroughly in distilled water. 

7. Dehydrate in absolute alcohol. 

8. Clear in xylol, carbol-xylol, or some essential oil. 

9. Mount in balsam. 

13. Pal's Modification of Weigert's Stain for the Medullary Sheath 
of Nerves. — This method is useful for the study of the central ner- 
vous system, and may, with advantage, be preceded by staining 
with neutral carmine. The tissues should have been fixed in a 
chromate solution; e.g., Miiller's fluid. 

1. Soak sections several hours in 1 per cent, chromic acid solu- 
tion in water. 

2. Stain twenty-four to forty-eight hours in : 

Hematoxylin crystals, 1 gram. 

Absolute alcohol, 10 cc. 

Lithium carbonate (saturated aqueous solution), 7 " 
Distilled water, 90 " 

The hymatoxylin crystals may be dissolved in the alcohol and 
the solution kept in stock, the proper proportions of lithium carbon- 
ate solution and water being added at the time of use. 

3. Wash in water to which a little lithium carbonate solution has 
been added (about 2 cc. to each 100 cc. of water). The sections 
should acquire a deep-blue color. 

4. Diiferentiate in 0.25 per cent, solution of potassium perman- 
ganate in distilled water, till the gray matter — e. g., of the spinal 
cord — becomes brownish-yellow (one-half to five minutes). 

5. Decolorize the gray matter in the following solution : 

Oxalic acid, 1 gram, 

Potassium sulphite, 1 " 

Distilled water, 200 cc. 

6. Wash thoroughly in distilled water. 

7. Dehydrate in 95 per cent, alcohol. 

8. Clear in carbol-xylol, oil of bergamot, or oil of origanum. 

9. Mount in xylol-balsam or xylol-dammar. 

This method stains the myelin-sheaths of the medullated nerve- 


fibres a dark blue, nearly black, color. If it has been preceded by 
a stain with neutral carmine, the axis-cylinders of th(,' nerve-fibres 
will l)c stained red, and the nuclei of tiie nerve-cells will also 
appear red. 

14. Golgi's Methods. — These methods have yielded most excel- 
lent results in the study of the central nervous system, the dis- 
tribution of the peripheral nerves, an<l the delicate terminations 
of the ducts of glands; c.(/., the bile-capillaries. The methods 
must be regarded as special procedures in such studies, and can 
but be referred to here. They all depend upon hardening in some 
chromium salt, with or without the addition of osmic acid, and the 
subsequent impregnation with silver nitrate. A precipitate is thus 
produced on or within certain of the elements in the specimen, giving 
them a dark-brown or black color. The methods are capricious, 
and not all of the tissue-elements of like character in the specimen 
are rendered prominent. This is an advantage, but necessitates 
a degree of care in the interpretation of the results. Furthermore, 
irrelevant precipitates may form in the tissues which have no 
definite relations to any structure. Considerable practice is, there- 
fore, required for the successful employment of all these methods, 
not only for a satisfactory execution of the manipulations, but also 
in the study of the results. The methods have no value for the 
study of cell-structure, since the whole cell is either covered or 
filled with the precipitates formed during the impregnation with 

Golgi has divided his methods into three groups : the slow, the 
ra])id, and the mixed. For the details of these methods and of 
the various modifications introduced by different investigators the 
student is referred to the journals on microscopy. It must suffice 
to state here that the slow method begins with a hardenine: of the 
tissues in a 2 per cent, solution of potassium bichromate, which is 
gradually raised to 5 per cent. This hardening takes from fifteen 
days to three months. In the rapid method the tissues are first 
hardened in a mixture of 4 parts of a 2 per cent, solution of potas- 
sium bichromate and 1 part of a 1 per cent, solution of osmic acid. 
The tissues remain in this mixture for from two to six days, when 
they are ready for im])regnation. For either method the pieces 
of tissue should not be thicker than 1.5 cm. 


Methods of Dehydration. 

The final manipulation in nearly all the methods for staining 
described above is a washing of the sections in water. This water 
must be removed before permanent mounts can be made. Dehy- 
dration is accomplished by treating the sections with alcohol. If 
they are impregnated, or have been embedded in collodion or cel- 
loidin, they must not be dehydrated in absolute alcohol, as that dis- 
solves the collodion. In such cases 95 per cent, alcohol is employed, 
the sections being treated with two baths of alcohol. When sections 
have been stained with carmine a contrast-stain may be obtained by 
adding a fev/ small crystals of picric acid to the first dish of dehy- 
drating alcohol. The excess of picric acid is then removed by the 
alcohol in the second dish. Absolute alcohol may be used for dehy- 
dration when the sections have not been embedded in collodion or 

When anilin-dyes have been used to stain sections it must be 
borne in mind that alcohol not merely dehydrates, but also differ- 
entiates the stain. If the sections are left too long in the alcohol, 
they may lose more color than is desired. 

Sections that are to be mounted in glycerin or glycerin-jelly 
require no dehydration, but can be mounted directly from water. 

Methods of Clearing. 

Clearing is necessary when specimens are to be permanently 
mounted in Canada balsam or dammar. Its object is to impreg- 
nate the section with some liquid that will drive out alcohol and 
also be miscible with the resin used for mounting. Of these clear- 
ing-agents there is a large number, from which a choice must be 
made according to the method of embedding that has been employed 
and the nature of the dye with which the tissues have been stained. 
Clearing-agents also differ in their miscibility with water, some 
requiring dehydration with absolute alcohol, others clearing well 
when 95 per cent, alcohol has been used for dehydration. 

1. Xylol. — This is an excellent clearing-agent when the sections 
have been well dehydrated with absolute alcohol. It does not 
injure anilin-dyes. It is, perhaps, the best clearing-agent for 
sections of tissue stained with borax-carmine before cutting, when 
no counter-stain is employed. Xylol then both removes the paraffin 
in the section and clears it. 


2. Carbol-xylol. — 

Carbolic acid crystals (melted), 1 vol. 

Xylol, ' 3 vols. 

This mixture is much more tolerant of water than pure xylol. 
Sections dehvtl rated in 9o per cent, alcohol may be cleared with 
this reagent, which does not dissolve collodion. The carbolic acid 
used should be pure, but need not be the more expensive synthetic 

3. Oil of Bergamot. — This light-green essential oil clears well and 
does not dissolve collodion. It may be used when 95 per cent, 
alcohol has been employed for dehydrating. 

4. Oil of Origanum. — The oleum origani cretici should be used. 
It is of light-brown color and clears sections dehydrated in 95 per 
cent, alcohol or stronger. It slowly discharges anilin-colors. 

5. Oil of Cloves. — This clearing-agent dissolves collodion and 
discharges anilin-colors. It may be used when it is desired to get 
rid of the collodion used for embedding after the sections have been 
stained. This removal is favored by dehydration in absolute alcohol 
before clearing. 

6. Oil of Cedar-wood. — This, when pure, has a very light-yellow 
color and smells like cedar-wood. It should be free from the more 
pungent odor of the oil derived from the leaves. This essential 
oil does not discharge anilin-colors, and is, therefore, useful when 
those dyes have been employed. It clears slowly, but well, and 
may be used after dehydration with 95 per cent, alcohol. 

Methods of Mounting. 

Sections that have been treated by the foregoing methods of 
preparation are fitted for mounting in a solution of some resin. 
The most commonly employed are Canada balsam and dammar. 
The best solvent for these resins is xylol, though chloroform and 
benzol are sometimes used for this [)urpose. All tmces of turpen- 
tine should be removed from the balsam before its solution, to avoid 
the discharge of stains with hsematoxyliu or anilin-dyes which tur- 
pentine occasions. 

When sections are transferred from alcohol to a clearing-agent 
they float upon the surface of the latter, and can then be flattened 
and all folds removed. As the alcohol is extracted the sections 


sink in the clearing-agent. In order to transfer them from the 
clearing-agent to a slide, the first step in mounting, a good method 
is to slip a strip of cigarette-paper under the section, withdraw it 
along with the section (using a platinum needle as aid, if necessary), 
drain off the superfluous fluid, and then lay the cigarette-paper on 
the slide, section side down. Light pressure will now squeeze out 
considerable of the clearing-agent, when the paper can be stripped 
from the section and slide, leaving the section nearly dry and with- 
out folds or wrinkles. With a little care, this method of transferring 
the section to the slide rarely fails. When such is the case the 
manipulations must be repeated. 

A drop of the mounting-medium is now placed upon the section 
and a cover-glass laid on and gently pressed down until it comes in 
contact with the section and the excess of balsam or dammar is 
expelled from beneath the cover. If the sections tend to raise the 
cover, the latter may be weighted with a bullet placed in its centre. 
Freshly mounted specimens are not so favorable for examination 
with high powers as those that have been mounted for a few hours 
or days. This is because the refractive indices of the clearing-agent 
and mounting-medium are not identical. When these have become 
thoroughly mixed, or the former has evaporated, the specimen is 
impregnated with and surrounded by a homogeneous medium that 
does not scatter the light passing through it. 

Canada balsam has a somewhat higher refractive index than 
dammar. It therefore renders the sections a little more transparent 
and more completely obliterates the structure-picture. When it is 
desired to retain as much of the structure-picture as possible, 
which is usually the case, dammar should be chosen for the mount- 
ing-medium. It dries a little more slowly than balsam, but soon is 
sufficiently dry at the edges of the cover-glass to preserve the sec- 
tion from injury. If the slides are kept in a horizontal position, 
in a warm place (40° to 50° C. ; 104° to 122° F.), for a couple of 
days, they will be dry enough for storage, but for several weeks 
must 1)0 handled with care. 

Stained sections may be examined in glycerin, having been 
mounted by the same manipulations as thos(! used for mounting 
in balsam, without previous dehydration or clearing. Such mounts 
are, however, difficult of preservation. The various cements that 
have been recommended for fastening the edges of the cover-glass 
to tlie slide are usually inefficient, as the changes of temperature 


that are inevitable cause tlie glycerin t() make its way between the 
glass and cement, loosening the latter. 

A better medium than glycerin for sections that cannot be sub- 
jected to the action of alcohol for the purpose of dehydration is 
glycerin-jelly. This is prepared by soaking the best French gelatin 
in cold water until it has imbibed all it will readily take up, then 
melting the gelatin, after pouring otf the excess of water, and 
adding an equal bulk of glycerin. A little carbolic acid may be 
added to the mixture to preserve it. The manipulations for mount- 
ing are similar to those given above, the sections being transferred 
from water to the slide. The glycerin-jelly may be melted and a 
drop placed uj)on the section, or a little lump of the solid jelly may 
be placed upon a cover-glass, melted by gentle heat, and the cover- 
glass then inverted over the section on the slide. After the jelly 
has dried at the edges of the cover-glass they may be painted with 
xylol balsam, dammar, or some cement. 

The Rapid Preparation of Sections for Diagnosis. 

The most expeditious means of obtaining sections of fresh tis- 
sues is to cut them without preliminary treatment with reagents, 
either free hand with a razor, or with the aid of a freezing mi- 
crotome (page 415). Such sections may be stained with methylene- 
blue (aqueous solution, page 423), or they may be examined in 
neutral salt solution. If they are to be stained, spread them out 
on a slide, pour a few drops of the methylene-blue solution over 
them, and, after a few moments, wash off the dye with water and 
cover the section. If such rapid work is not necessary, the sections 
can be fixed in formalin (page 416), and, after washing out that 
reagent, stained. Such sections may be hardened and dehydrated, 
by placing them in dishes of increasingly strong alcohols, and 
finally mounted in dammar ; but the results are by no means so 
good as when fixation and hardening are done before sections are cut. 

When time is not pressing the following method will give good 
results : 

1. Fix and harden pieces not over l inch thick in absolute alcohol 
on quick-lime over night (page 407). 

2. Dip the specimen in thick collodion and embed it on a glass 
block by the rapid method (page 412). When the block has been in 
80 per cent, alcohol for three or four hours it may be cut ; but it is 
better to let the collodion harden for twenty-four hours. 


3. Stain ^^^th hsematoxylin and eosin (page 418), cutting short the 
time of washing after the hsematoxylin, if in a hurry. 

4. Dehydrate in 95 per cent, alcohol ; two successive baths. 

5. Clear in carbol-xylol. 

6. Mount in xylol-dammar. 

Very serviceable sections can be prepared in less than twenty- 
four hours by this method, and the specimens, though not of the 
best quality, will be permanent, and may be kept for future refer- 

Special Methods. 

The foregoing methods are for the preparation of tissues from 
which sections must be made before they are fit for examination 
under the microscope. The physician is, however, frequently called 
upon to examine other objects, when the following directions will be 
found useful. 

1. Examination of Urinary and other Sediments. — For the collec- 
tion of the sediment vessels with vertical walls should be used, not 
conical glasses. A test-tube answers very well. The sediment 
should be allowed to settle for several hours in a cool place, to 
avoid decomposition ; or, better, the sediment should be precipitated 
by means of a centrifuge. It should be borne in mind that urine 
becomes alkaline during decomposition, and that the ammonia pro- 
duced causes changes in the characters of the crystalline or other 
inorganic constituents of the sediment, and also renders the identi- 
fication of the organic constituents difficult or impossible. 

When the sediment has collected at the bottom of the vessel a 
portion should be removed with a pipette for examination. Place 
the finger over one end of the pipette before introducing it into 
the liquid, to retain the air, then place the other end in contact 
with the sediment and allow the air to escape slowly by raising or 
moving the finger a little. Close the upper end of the pipette and 
withdraw it. Now carefully wipe the outside of the pipette and let 
tlie fluid escape until a good sample of the sediment is at the end of 
the tube. Place a drop of this sediment on a slide and cover. Ex- 
amine the specimen with a low power at first, taking care to use a 
very small diaphragm. In this way the presence of urinary casts 
may be more rapidly determined than if a high power is used. 
When there is douljt as to a given object being a cast examine it with 
a higher power. After the specimen has been examined for casts 
and other objects large enough to be identified with a low power, 


use the high power for the detection of red blood-corpuscles, pus, 
etc. Objects in urinary sediments may be stained with aqueous 
methykMie-l)lue, (Jrani's solution of iodine, or alum-carmint! ; or 
their chemical nature determined by means of microchemical reac- 

2. Preparation of Cover-glass Smears. — These are used for the 
examination of blood, pus, sputa, cultures of bacteria, etc., when it 
is desired to employ stains. They are also employed occasionally 
for the study of some of the constituents of soft tissues. 

A small drop, or fragment, of the specimen is placed between 
two cover-glasses. If the specimen is sufficiently fluid, it will at 
once spread out into a thin layer between the covers. When this 
is not the case pressure may be used. The covers are then drawn 
apart, not lifted, leaving a coating upon both. They are allowed to 
dry spontaneously, after which the film is fixed by passing the 
cover-glasses three times through a flame, care being taken not to 
scorch the film, which should not come in contact with the flame. 
Heat applied through the glass to the dry film will render it insol- 
uble and affix it to the cover. The constituents of the film may 
then be stained on the cover-glass, the latter being either floated 
on the dye or immersed in it as though it were a section. Hsema- 
toxylin and eosin may be employed ; but anilin-dyes, such as meth- 
ylene-blue, carbol-fuchsin, anilin-gentian-violet, etc., are more com- 
monly used. 

3. Examination of Sputa for Tubercle Bacilli. — The small cheesy 
])articles in the sputa are most likely to contain tubercle bacilli. 
Cover-glass smears are stained by the following method : 

a. Stain fifteen minutes in freshly filtered carbol-fuchsin at the 
room-temperature, or heat until vapors rise from the surface of the 
dye, and maintain that temperature for about three minutes. 

b. Wash off the excess of dye with water. 

('. Differentiate in dilute sulphuric acid, prepared by adding 5 cc. 
of pure acid to 95 cc, of distilled water, until the cover-glass has 
only a fiiint tinge of pink when the acid is washed off with water. 

d. Wash in water to remove the acid. 

e. Counterstain with aqueous methylene-blue for two minutes. 
/. Wash in water. 

(J. Dry the cover-glass and mount it, film side down, on a drop 
of xylol-dammar. 

The tubercle bacilli will be stained red, while other bacteria and 



the nuclei of cells will be blue. This method, like all others used 
for the detection of the tubercle bacillus, depends upon the fact that 
that bacillus takes up colors with reluctance, but, after staining, 
holds them tenaciously. The specimen is therefore first stained 
with a strong dye, is then decolorized with some agent that will 
discharge the color from all bacteria except the tubercle bacillus 
(and spores, which, however, have a different shape from that of 
the tubercle bacillus), and afterward stained with a weaker dye of 
another color which is imparted to the bacteria that have been 

4. Examination of Urethral Pus for the G-onococcus. — The gono- 
coccus is shaped a little like a coflPee-bean, and usually occurs in 
pairs with the flattened surfaces of the individual cocci facing each 
other. In pus it is frequently situated within the leucocytes, while 
the other varieties of pyogenic cocci usually lie outside of the pus- 
corpuscles. The gonococcus is decolorized by treatment with Gram's 
iodiu solution followed by alcohol ; the more common cocci found 
in suppuration are not decolorized. These diiferences in shape, sit- 
uation, and behavior toward dyes serve to distinguish the gonococci 
from the other cocci that may be present. The smears, fixed by 
heat, are stained as follows : 

a. Stain for five minutes in freshly filtered anilin-gentian-violet. 

b. Wash off excess of dye with w^ater. 

c. Immerse in Gram's solution for two minutes. 

d. Decolorize in 95 per cent, alcohol till no more color is given off. 

e. Stain two minutes in aqueous fucbsin, prepared in a manner 
similar to that used for aqueous methylene-blue. Bismarck-brown 
may be used for this counterstain in place of the fuchsin. 

/. Wash in water, dry, and mount in dammar or balsam. The 
gonococci will be stained by the second dye used ; other cocci be- 
longing to the pyogenic group will be a dark purple, they having 
retained the color first imparted to all the bacteria by the gentian- 
violet. In this case the gonococci are distinguished from the other 
cocci by taking advantage of the fact that they are "negative to 
Gram," while the others are "positive." 

5. Examination of Blood-smears. — Htematoxylin, followed by a 
strong counterstain with eosin, will furnish useful specimens for 
most purposes. The ditl'erentiation of the various granules in the 
white corpuscles described by Ehrlich requires special methods, for 
a description of which the reader is referred to special works on the 


blood or clinical niicroseopv. The malarial plasniodia arc best 
detected in ])erfectly fresh blood, exaininetl innncdiately with an 
inunerslon-lens, when their changes of form serve to make them 
more easily recognizable than when they are songlit in smears. In 
the latter tln'V may be stained by the following method : 

a. Fix the lihn by means of heat, or, better, by immersion in 
absolnte alcohol for half an honr. (In the latter case wash off the 
alcohol with water before staining.) 

b. Stain for several hours in Chenzinsky-Pehn's stain : 

Concentrated alcoholic solution of methylene-blue, 10 cc. 
0.5 per cent, solution of eosin in 70 per cent, alcohol, 5 cc. 
Distilled water, 10 cc. 

The solution should be filtered before, and preserved from evap- 
oration during, the staining. 

c. AVash in water, dry, mount in xylol-dammar. 

The malarial plasmodia will be stained blue, the body of the red 
corpuscles red, the nuclei of the leucocytes blue, and eosinophile 
granules, within those cells, red. 

6. Examination of Bacteria in Cover-glass Preparations. — If the bac- 
teria are already in a fluid, a drop is placed upon a cover-glass, spread 
over its surface, allowed to dry spontaneously, and then fixed by heat, 
as described above. If cultures on solid media are to be examined, 
a drop of water is first placed upon the cover-glass, and a little 
mass of the bacteria disseminated through it, and then the mixture 
is spread in a thin layer by means of the platinum needle. It is 
then dried and fixed, as in the preceding case. Such preparations 
may be stained with methylene-blue, carbol-fuchsin, by Gram's 
method (anilin-gentian-violet, followed by Gram's iodine solution, 
and then alcohol), or with some other anilin-dye. For the diph- 
theria or typhoid bacillus an alkaline methylene-blue (see Unna's 
formula) serves well. 

7. Examination in Hanging Drop. — This method is useful for the 
observation of objects suspended in a fluid. It is extensively used 
in bacteriology for the study of living bacteria. A drop of the 
fluid is placed on th.e centre of a cover-glass, which is then inverted 
over the concavity in a hollowed slide. The edges of the cover- 
glass should then be sealed with a dr<)[) of water or oil, to jjrevent 
evaporation of the hanging drop. 


8. Microchemical Reactions. — These reactions are resorted to to 
determine the chemical nature of objects under the microscope. 
Every stain is the result of a microchemical reaction, but as yet 
the knowledge obtained by staining tissues cannot always be ex- 
pressed in chemical language. 

The manipulations are usually so conducted that the reaction can 
be directly observed under the microscope. The object to be studied 
is placed in the middle of the field. The reagent used is then 
placed at one edge of the cover-glass, whence some of it will flow 
beneath the latter. To facilitate the entrance of the reagent a nar- 
row strip of filter-paper may be brought in contact with the oppo- 
site edge of the cover, withdrawing some of the fluid from beneath 
it. It is best to sharpen the end of the strip which comes in con- 
tact -with the cover-glass, so that the absorption of fluid shall be 
slow ; otherwise the currents induced will be likely to wash the 
object from the field of vision. The following tests, applied in this 
way, may be of use : 

a. Urates. Insoluble in 1 per cent, acetic acid ; soluble, on the 
application of heat, in water (or urine). The slide must be removed 
from the microscope when heat is applied to it. 

h. Earthy phosphates. Dissolve on the addition of 1 per cent. 
acetic acid. Are not dissolved by heat. 

c. Calcium oxalate. Insoluble in 1 per cent, acetic acid ; soluble 
in 1 per cent, hydrochloric acid. 

d. Carbonates. Soluble in 1 per cent, acetic acid or hydrochloric 
acid, with evolution of gas-bubbles. 

e. Albuminoid granules. Become indistinct, and finally invisible, 
on the addition of 1 per cent, acetic acid or 1 per cent, potassium 
hydrate ; not blackened by osmic acid. 

/. Fatty granules. Not affected by 1 per cent, acetic acid or 1 
per cent, potassium hydrate. Stained black or dark brown by osmic 

cj. Starch. Stained dark blue to black by iodine solutions. Use 
Gram's solution. 

h. Cellulose. Stained yellow by iodine solutions. If the water 
be tlien removed and concentrated sulphuric acid introduced, the 
color becomes blue. The walls of most vegetable cells are composed 
of cellulose. 

i. Teichmann's test for haemoglobin. This test depends upon the 
conversion of the haemoglobin or its derivatives into hsemin, which 


crystallizes in rhombic plates of" a reddisli-brown color. The hicmin 
is produced by heating with a little salt and strong acetic acid. 
Evaporate a drop of neiitnd salt solution to dryness on a slide. 
Place the substance to be tested upon it and cover. Fill the space 
between cover and slide with glacial acetic acid and heat over a 
flame till bubbles begin to form. Maintain that heat for a few 
minutes, replacing loss by fresh additions of acetic acid. Let the 
slide cool slowly, and, when cold, examine. If the results are nega- 
tive, repeat the heating with acetic acid. The acid should not 
actually boil, but should be kept at the point of incipient ebullition. 

j. Tests for amyloid substance. Sections of fresh tissue may be 
soaked for some time in Gram's solution, then washed and examined 
in water. Amyloid substance is stained reddish-brown, the tissues 
yellow. Sections of tissues fixed in alcohol, corrosive sublimate, or 
formaldehyde, may be stained in a solution of 1 per cent, methyl- 
violet dissolved in distilled water, without the addition of alcohol. 
The sections are then washed in 1 per cent, hydrochloric acid for 
the purpose of difi'erentiating the stain. After thorough washing 
in several changes of water they may be mounted in glycerin-jelly. 
The amyloid substance is stained reddish-violet, the other tissues 

k. Test for iron in pigmentations. The iron from the hemo- 
globin of the blood is sometimes present in the pigmentation result- 
ing from old extravasations, in the form of hremosiderin. The 
same compound is also sometimes found in the tissues in cases of 
pernicious anaemia. The presence of iron in this pigmentation may 
be demonstrated by the following method : 

(rt) The tissues should be fixed in alcohol. 

(6) Soak the section in a 2 per cent, solution of potassium ferro- 
cyanide for ten minutes. 

(c) Transfer to Orth's acid alcohol (page 422) for five or ten 

The sections may now be examined in a glycerin-mount with a 
wide diaphragm, or they may be counterstained, for which purpose 
treat as follows : 

(c?) AV^ash with water. 

(e) Stain with Orth's lithio-carmine. 

(/) Dehydrate and mount in xylol-daramar. 

The iron in the section is converted into Prussian blue ; the nuclei 
of the cells, when the countcrstain has been employed, are red. 


I. Examination of sputa for elastic fibres. In pulmonary disease 
involving a destruction of pulmonary tissue and the appearance of 
fragments in the expectoration, elastic fibres from the alveolar walls 
may frequently be found in the sputa : 

Fill a test-tube one-third full of sputa, add five or six drops of 
36 per cent, potassium hydrate solution, and boil the mixture for 
three or four minutes. Add an equal bulk of distilled water. 
Divide the contents of the tube between the two tubes of the cen- 
trifuge and precipitate their contents. If elastic fibres were pres- 
ent, they will be found either in the sediment or in the scum on the 
top of the fluid. 

9. Methods of Maceration. — 

a. One -third alcohol. 

95 per cent, alcohol, 35 cc. 

Distilled water, 65 " 

This dilute alcohol is excellent for the separation of epithelium 
from the surfaces of mucous membranes. The fresh tissues are 
placed in the alcohol for a day or two, after M'hich the cells can 
easily be detached and separated by shaking. The cells are well 
preserved, and may be stained with methylene-blue or alum-car- 

h. Potassium hydrate. 

Potassium hydrate, pure by alcohol, 36 grams. 

Distilled water, 64 cc. 

The solution should be cold before use. It cannot be filtered 
through paper ; but if not clear, should be decanted from any sedi- 
ment, or a fresh solution prepared. Maceration takes place very 
quickly in this solution. The tissues can usually be teased apart 
within fifteen to thirty minutes. They must be examined in the 
potash solution vnthont dilution, as the addition of water quickly 
destroys the tissue-elements. For this reason the specimens to be 
macerated should be placed in several times their bulk of the pot- 
ash solution ; otherwise the water they contain will dilute the pot- 
ash. Permanent mounts cannot be made. 

c. Chromic acid. A solution of 1 part of the acid in 10,000 
parts of distilled water will fiicilitate the teasing apart of tissue- 
elements which have macerated in it for one to several days. After 
careful washing on tlie slide alum-carmine alone, or followed by 
picric acid, may be used for staining. 


10. Methods of Decalcification. — Tissues which contain calcified 
nodules or bono must be freed IVoiu lime-salts before they can be 
cut. It is dittioult to do this raj)idly witliout injury to the softer 
tissue-elements. When good results are desired, and the necessary 
time can be afforded, the tissues should first be fixed and hardened, 
small pieces being selected. Zenker's tluid fixes Avell for this ])ur- 
pose, but Orth's fluid or alcohol may be used. If Zenker's or Orth's 
fluid is used, the tissues must be washed in water and hardened in 
alcohol for at least a day before they are decalcified (see Methods of 
Fixing and Hardening, pp. 403, 408). 

Decalcification is accomplished by treatment Avith acids. Five 
per cent, nitric acid will decalcify small pieces of bone in from one 
to five days. The progress of the decalcification may be deter- 
mined by pricking the tissue with a needle, but after it appears 
to be soft it is well to continue the action of the acid for a day or 
two, lest some undissolved particles should remain and injure the 
edge of the microtome-knife. A saturated aqupous solution of 
picric acid is sometimes used for decalcifying. Its action is very 
slow, though not injurious to the tissues, which require no prelimi- 
nary treatment, the picric acid acting as a fixing and decalcifying 

After decalcifying in nitric acid the tissues should be thoroughly 
washed in running water for twenty-four hours and then rehardened 
in alcohol, after which they may be embedded. After decalcifying 
in picric acid the tissues are placed in 70 per cent, alcohol and hard- 
ened without previous washing in water. 

AVhen rapid decalcification is necessary nitric acid and phloro- 
glucin, which restrains the destructive action of the acid, may be 
used. The solution is prepared by dissolving 1 gram of phloro- 
glucin in 10 cc. of pure nitric acid. To this 100 cc. of 10 per cent, 
nitric acid are added. Decalcification takes place within a few hours 
in this solution, which contains about 20 per cent, of nitric acid. 
The tissues should then be washed and hardened. 

Another rapid method which combines decalcification Mith hard- 
ening is to place the fresh tissues in a large bulk of 5 per cent, 
nitric acid in 80 per cent, alcohol. After decalcification has taken 
place the tissues are liardened in alcohols of increasing strength, 
large quantities being used in order to remove the acid. Before 
staining, the sections should be washed thoroughly in water to get 
rid of any residual traces of acid. 


A BSCESS, 312 
A cold, 319 
Absorption, 295 
Achroniatui, 34 
Acidopliilic cells, 119 
Active hypeni'mia, '298 
Acute intlainniation, 297 

parenolivinatous intlammation, 268 
nephritis, 272 
Adeno-carcinonia, 390 
Adeno-fibroma, 377 
Adenoma, 370 
Adipose tissue, 78 
Adrenal bodies, 186 
Adventitia, 112 
Akronicgaly, 191 
Albumin, Mayer's, 417 
Albuminoid degeneration, 266 
Alcohol, absolute, 407 
Alveoli, pulmonary, 171 
Amoeba, 28 
Amyloid infiltration, 281 

substance, tests for, 437 
Anaemic infarcts, 332 
Angiomata. 373 
Angiomatous tumors, 373 
Anilin-water, 424 
Areolar tissue, 76 
Arteries, 110 

lielicine, 223 
Association-fibres of cerebrum, 249 

of spinal cord, 239 
Atrophy, 284 

functional, 284 

pressure-, 285 

senile, 287 
Attraction-spheres, 35 
Axis-cylinder, 97 

BACTERIA, examination of, 435 
Basement-membrane, 58 
Basophilic leucocytes, 126 
Bergamot, oil of, 429 
Bladder, 164 
Blood, 122 

-plates, 126 

-smears, preparation of, 434 
Bodies, adrenal, 186 

Malpighian, 154 

Bodies, Malpighian, of spleen, 177 

Pacinian, 252 

pearl-, 390 

polar, 35, 217 
Body, pituitary, 139 
Bone, 68 

canaliculi of, 68 

general character of, 68 

Haversian canals of, 68 

lacunae of, 68 

-marrow, 71, 119 
red, 119 . 
yellow, 119 

regeneration of, 338 
Bowman, glands of, 255 
Bowman's capsule, 159 
Bronchi, 169 
Bronchioles, 170 
Broncho-pneumonia, 317 
Brownian movement, 29 
Brunner, glands of, 141 
Bulb, olfactory, 258 
glomeruli of, 257 

CACHEXIA strumipriva, 183 
Calcareous infiltration, 282 
Calcium oxalate, tests for, 436 
Callus, 309 

Canada-balsam, 428, 430 
Capillaries, 113 
Capsule, Bowman's, 159 

Glisson's, 146 
Capsules, supra-renal, 186 
Carbol-fuchsin. 423 
Carbonates, tests for, 436 
Carbo-xylol, 429 
Carcinoma, 382 

colloid, 388 

medullary, 384 

scirrhous, 384 

simple, 384 
Cardiac glands, 136 

muscles, 89 
Carmine, alum-, 421 

borax-, 421 

lithio-, 422 

neutral, 420 
Carotid glands, 194 
Cartilage, 64 




Cartilage, elastic, 67 

fibro-, (5(5 

general character of, 64 

hyaline, 66 

luatrix of, 65 

ossification of, 64 

regeneration of, 338 
Catarrhal inflammations, 316 

pneumonia, 317 
Cedar-wood, oil of, 429 
Cell, or cells, 27 

acidophilic, 119 

compound granule-, 316 

decidual, 215 

of Deiters, 260 

-division, 40 
amitotic, 40 
centrosorae in, 34 

ganglion-, 95 

giant-, 40, 119 

glia-, 101 

goblet-, 52, 139 

hair-, 260 

migratory, 124 

mitral, 258 

of Miiller, 262 

nerve-, 95 

organs of, 31 

plasma-, 120 

prickle-, 55 

of Purkinje, 243 

reproduction of, 34 

of Sertoli, 225 

stellate, 245 

sustentacular, of retina, 261 
in testis, 227 

wandering, 124 
Cellulose, tests for, 436 
Centrosome, 31 
Cerebellum, 243 
Cerebrum, 246 

association-fibres of, 250 

commissure-fibres of, 249 

projection-fibres of, 249 
Cheesy degeneration, 274 
Cheniotactic .substances, 309 
Chemotaxis, 309 
Chondroma, 350 
Chromatin, 34 

reduction of, 226 
Chromolysis, 294 
Chromf)plasm, 34 
Chromosomes, 37 
Chronic inflammations, 322 
interstitial, 324 
parenchymatous, 269 
Chyle, 126 

Cicatricial tissue, 308 
Ciliated epithelium, 53 
Circulatory system, 108 
Cirrhosis of liver, 323 
Clarke, column of, 241 
Clearing, methods of, 428 

Clearing, methods of, bergamot, oil of, 429 
carbol-xylol, 429 
cedar-wood, oil of, 429 
cloves, oil of, 429 
origanum, oil of, 429 
xylol, 428 
Clefts of Lantermann, 99 
Cloves, oil of, 429 
Coagulation, explanation of, 127 

-necrosis, 294 
Coccygeal gland, 195 
Collateral fibres of spinal cord, 239 
Colliquative necrosis, 295 
Collodion, 409, 412 
Colloid, 181 

carcinoma, 388 

degeneration, 278 
Colon, 142 
Colostrum, 219 

-corpuscles, 219 
Column of Clarke, 241 
Columnar epithelium, 52 
Commissure-fibres of cerebrum, 249 
Compensatory hypertrophy, 289 
Congestion, passive, 326 
Connective tissue, 63 

tumors, 347 
Contractile substance, 83 
Cord, spinal, 236 
Corium, 196 
Corpora amylacea, 224 
Corpus album, 210 

cavernosum, 222 

ha?morrhagicum, 210 

luteum, 210 

spongiosum, 222 
Corpuscles, colostrum-, 219 

genital, 253 

of Krause, 253 

of Meissner, 253 

red, 123 

tactile, 252 

white, 124 
Croupous inflammation, 317 

membrane, 319 
Crypts of Lieberkiihn, 139 
Cubical epithelium, 49 
Cuticle of epitlielium, 50 
Cuticiilarized epithelium, 54 
Cutting, methods ol', 415 
free-liand, 415 
frozen sections, 415 
celloidin sections, 416 
collodion sections, 416 
Cylindroma, 356 
Cystoma, 392 
Cytoplasm, 29, 32 

DECALCIFICATION, methods of, 439 
Decidual cells, 215 
Degenerations, 265 
albuminoid, 266 
cheesy, 274 



Defjenerations, colloid, 278 

fattv, 2GG 

hya'liiu'. 280 

keratoid, '280 

imicous, 277 

of nerves, 283 

pareiicliymatous, 266 
Dehydration, methods of, 428 
Deiters' cells, 2(30 
Dendrite, 234 
Deinioid cysts, 392 
Developmental hypertrophy, 230 
Diapedesis, 301 

Diaster-phase of karyokinesis, 38 
Digestive organs, 128 
Diphtheritic inflammation, 318 

membrane, 294 
Discus proligerus, 209 
Dispirem-phase of karyokinesis, 38 
Ductless glands, 62, 180 
Duodenum, 137 

Ectoplasm, 29 
Elastic cartilage, 67 

fibres, 73 
Eleidin, 19S 
Elements, sarcous, 93 
Elementary tissues, 41 
Embedding, methods of, 411 
celloidin, 412 
collodion, 412 
parartin, 413 
Embolism, 330 
Embryonic layers, 22 
Encapsulation, 296 
Endoderm, 20 
Endoneurium, 100 
Endoplasm. 29 
E)ndothelioraa, 355 
Endothelium, 45 

functions of, 48 

general characters of, 45 

regeneration of, 336 
Energy, kinetic, 18 

potential, 18 
Eosin, 420 

Eosinophilic leucocytes, 126 
Epicardium. 109 
Epidermis, 197 
I^pididvmis, 225 
f:piglottis, 1G8 
Epineurium, 100 
Epithelial tumors, 376 
Epithelioma, 391 
Epithelium, 49 

ciliated, 53 

columnar, 52 

cubical. 49 

cuticle of, 50 

cuticularized, 54 

functions of. 41, 57 
activities of, 57 

Epitheliinn, general characters of, 49 

germinal, 207 

glandular, 50 

pavement-, 51 

regeneration of, 336 

stratified, 54 

transitional, 56 
Erectile tissue, 222 
Erythroblasts, 119 
External genitals, 217 
Exudate, infiammalory, 301 

FALLOPIAN tubes, 210 
Fatty degeneration, 266 
infiltration, 574 
Fibres, a.ssociat ion-, of cerebrum, 250 
of cord, 239 
collateral, of cord, 239 
commissure-, of cerebrum, 249 
connective-tissue, staining, 425 
elastic, 73 
moss-, 246 
nerve-, 96 

staining, 426 
projection-, of cerebrum, 249 
Sharpey's, 70 
white, 73 
yellow, 73 
Fibrin, 126 

Fibrinous inflammation, 313 
Fibro-cartilage, 66 
Fibroma, 347 
Fibrous tissues, general character of, 72 

regeneration of, 336 
Figures, mitotic, preservation of, 406 
Fixation, metliods of, 403 
alcohol, absolute, 407 
boiling, 408 

Flemming's solution, 406 
formaldehyde, 405 
mercuric chloride solution, 405 
Muller's fluid, 403 
Orth's fluid, 404 
Zenker's fluid, 404 
Flemming's solution, 406 
Follicles, Graafian, 207 

lymph-, 143 
Formaldehyde, 405 
Fractures, healing of, 308 
Functional atropliy, 284 
hypertrophy, 288 

Ganglion-cells, 95, 234 
Gangrene. 296 

drv, 296 

moist, 296 
Genital corpuscles, 253 
Gentian-violet. 423 
Germinal epithelium of ovary, 207 
(4iant-cell sarcoma, 367 
Giant-cells, 40, 119 
Gianuzzi, crescents of, 131 



Gland, mammary, 218 

thyroid, 181 
Glands of Bowman, 255 

of Brunner, 141 

cardiac, of stomach, 136 

carotid, 194 

coccygeal, 195 

ductless, 62, 180 

lymphatic, 114 

parotid, 131 

pyloric, 136 

salivary, 131 

sebaceous, 201 

secreting, 58 

sublingual, 131 

submaxillary, 131 

sweat-, 198 
Glandular epithelium, 50 
Glioma, 394 
Glisson's capsule, 1 46 
Glomeruli, olfactory, 258 
Glomerulus, 158 
Glycerin, 430 

jelly, 431 
Glycogenic infiltration, 275 
Goblet-cells, 52, 139 
Gonococcus, staining of the, 434 
Graafian follicles, 207 

development of, 208 
Gram's solution, 424 
Granulation-tissue, 304 
Granules, albuminoid, tests for, 436 

fatty, tests for, 436 
Granulomata, 318 

Hsematoidin, 328 
Hfematoxylin, 418 
Haemoglobin, tests for, 436 
Hferaorrhage, 328 
Hsemosiderin, 328 
Hair, 199 

-cells, 260 

cuticle of, 200 

-follicles, 199 

development of, 204 
Hanging-drop preparations, 435 
Hardening, methods of, 408 
Haversian canals, 68 
Hearing, 259 
Heart, 109 

Helicine arteries, 223 
Henle, tuljes of, 155 
Hepatization of lung, gray, 313 

red, 313 
Hyaline cartilage, 66 

degeneration, 280 
Hyaloplasm, 29 
Hypera^mia, active, 298 

inflammatory, 298 

passive, 286, 326 
Hyperplasia, 288 

inflammatory, 290 

Hypertrophy, 288 

compensatory, 289 

developmental, 290 

functional, 288 

inflammatory, 290 
Hypophysis cerebri, 189 

TMPEEGNATION, methods of, 409 
1 celloidin, 409 
collodion, 409 
paraffin, 409 
Infarcts, 332 

anaemic, 332 

hsemorrhagic, 332 
Infiltration, amyloid, 281 

calcareous, 282 

fatty, 274 

glycogenic, 275 

serous, 276 
Infiltrations, 265 
Inflammation, acute, 297 
parenchymatous, 268 

catarrhal, 316 

chronic, 322 
interstitial, 324 
parenchymatous, 269 

croupous, 317 

diphtheritic, 318 

fibrinous, 313 

serous, 315 
Inflammatory exudate, 301 

hyperaemia, 298 

hyperplasia, 290 

hypertrophy, 290 

repair, 303 

stasis, 298 
Infundibula of lung, 171 
Interstitium, 106 
Intestine, small, 141 
Intima, 110 

Involuntary muscles, 88, 91 
Iron-hematoxylin stain, 425 

tests ibr, 437 

diaster-phase, 38 

dispirem-phase, 38 

monaster-phase, 37 

significance of, 39 

spirem-phase, 35 
Karyolvsis, 294 
Keloid,' 360 
Keratin, 198 

Keratoid degeneration, 280 
Kidney, cortex of, 153 

pelvis of, 163 

Malpighian bodies of, 154 
Kidneys, 153 ^ 

Kinetic energy, 18 
Krause, corpuscles of, 253 

Lantermann, clefts of, 99 



Larynx, IfiS 
Layers, embryonic, 22 
Leioiiiyoina, 870 
Leucocytes, 124 

basophilic, 126 

eniiji;rati(>n 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 



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 



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 


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 



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 


ARTS, 395 

White corpuscles, 124 
fibres, 73 

VYLOL, 428 
yELLOW fibres, 73 
^ENKER'S fluid, 404 

Cntnloguc of Books 


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