all. Frey regards them as artificial productions. 1
1 The most rational explanation is that furnished by F. E. Schultze. The intra-
fibrillar substance is, according to this observer, converted into hygroscopic mucin,
which swells up. This constitutes a change in the cell which, from being columnar,
becomes goblet-shaped. The wall finally ruptures, and the mucin is poured out.
Other varieties of epithelium will be taken up in connection
with the different organs. As already stated, many transi-
tional varieties occur, even in direct association with the typi-
cal forms we have described.
Structure of epithelial corpuscles. According to the views
of Heitzmann, Klein, and others, the substance of the cor-
puscle is pervaded by a network, the minute fibres of which
may be seen under a lens of high power. The nucleus or cen-
tral body is also similarly provided. Within the meshes of
this network there is a hyaline substance, the abundance or
paucity of which determines the size of the meshes.
The "granules," which have often been described, are, ac-
cording to this view, the nodal points of the mesh work. It
is also stated that the epithelial cells sometimes have a fine
limiting membrane (Klein) ; but even in such instances it IB
merely a condensation of the outer part of the corpuscle.
Within the nucleus there are also, according to the same ob-
servers, fibres, within the meshes of which are not infrequently
real granules (nucleoli). The epithelial corpuscles are at-
tached together, either by an interlacement of their processes,
as in the liver, or by a peculiar cement substance, as in pave-
ment epithelium, or by a continuity of their processes, as in the
Recent histological studies have narrowed the field formerly
occupied by the epithelial bodies, and, in accordance with
these views, the flattened corpuscles which cover serous mem-
branes, such as the pleura and peritoneum, will be arranged
under the connective-tissue series, rather than under the epi-
thelial. The reasons for this change will be given in a subse-
SCHULTZE, M. Die Stachel- und Riffzellen. Virchow's Arch., Vol. XXX., 1864,
SCHULTZE, F. E. Epithel. u. Driisenzellen. Arch. f. mikrosk. Anat. 1867.
RANVIER. Traite technique d'histologie. Paris, 1875.
DEL AFIELD. Studies in Pathological Anat. New York, 1878 et seq.
KLEIN and E. NOBLE SMITH. Atlas of Histology. 1879-80.
HEITZMANN. New York Medical Record, July 31, 1880, p. 133.
FREY. The Microscope and Microscopical Technology. New York, 1880.
THE CONNECTIVE SUBSTANCE GKOUP.
MUCOUS OR GELATINOUS TISSUE ; ADENOID TISSUE ; NEUROG-
LIA ; FAT TISSUE ; FIBROUS TISSUE PROPER ; CORNEAL TIS-
SUE ; INTERMUSCULAR TISSUE ; TENDON TISSUE ; ELASTIC
THE term connective substance was first proposed by Reich-
ert in 1845, and is now applied to a class of animal tissues whose
offices are very important in the economy. Prominent among
them is bone, which forms the solid framework of the body,
gives it strength, and supplies points of attachment for muscles
and tendons ; another group comprises the ligaments, which
assist in holding the bony parts, and also some organs, in their
proper relations ; others again, of a more delicate nature, fur-
nish support or protection for epithelial bodies, blood-vessels,
and nerves. Just at the present time the histology of connec-
tive substances has an important bearing on many points that
relate to inflammation, degeneration, and the development of
certain new growths, and it is therefore desirable to have a clear
conception of them. This object is best effected by studying
each variety separately, not only in its normal condition, but
under the changes it exhibits when acted on by the factors that
are concerned in the processes of disease.
It is a property of these substances that they supplant one
another at different times or under peculiar circumstances. As
an example, the hyaline cartilage of young life may change
into true bone in old age, while, on the other hand, there is
always a tendency for fully formed tissue, if inflamed, to re-
vert toward the embryonic type.
The connective substances may be subdivided as follows :
1, mucous or gelatinous tissue ; 2, adenoid tissue ; 3, neurog-
THE CONNECTIVE SUBSTANCE GEOUP.
lia ; 4, fat tissue ; 5, fibrous tissue proper ; 6, corneal tissue ;
7, intermuscular tissue ; 8, tendon tissue ; 9, elastic tissue ;
10, bone; 11, cartilage; 12, enamel; and 13, dentine. The
word connective tissue was first proposed by Johannes Mueller,
and is sometimes used as synonymous with connective sub-
stance, but erroneously. The former is merely a variety of the
latter, and is usually intended to indicate one or other of the
flexible connective substances that form the interstitial material
of the body, and in that sense we shall use it for convenience
sake, but without implying any special histological character.
In precise histological descriptions it is always best to use
the special name of the variety intended, such as mucous tis-
sue, adenoid tissue, and the like, where the structure happens
to be known.
It is also well to state here that the term "cellular" tissue,
found in many of our anatomies, is apt to mislead the student.
The word "cellular" has no reference to cells, i.e., corpuscles,
but to the large cavities or spaces that exist in all loose connec-
Fio 23. Gelatinous or mncous tissue. Human umbilical cord.
tive tissues, of which the subcutaneous is an example. These
spaces are easily seen by the naked eye, when inflated with air.
Mucous or gelatinous tissue. This is the most simple
form that is met with. It is seen to great advantage in the
embryonic umbilical cord, which also contains several other
varieties of connective tissue.
The following method has been found best suited to demon-
strate it. Take a small piece of cord at about the third month
and immerse it a few weeks in Mueller' s fluid ; make a thin sec-
tion through the very soft gelatinous part, then soak it a few
minutes in distilled water, to which subsequently a few drops
MANUAL OF HISTOLOGY.
of acetic acid are to be added so that the solution shall not con-
tain more than 1 per cent, of acid, and then mount in glyce-
rine. It will then be seen that the softest portion contains
numbers of irregularly-shaped, thin plates, some provided with
an oval, flattened nucleus, others having none that are appa-
rent (Fig. 23). Some of these flattened bodies anastomose by
these processes with those of other plates, others are quite free.
The substance tying between the cells, the intercellular sub-
stance, is quite homogeneous, or slightly granular, in the softest
portions, and has at first no defined fibrillation. In the neigh-
borhood of the former tissue, lines of fibrillation occur, while at
the same time these flattened bodies become smaller, although
they are still flattened (Fig. 24, b). Mucous or gelatinous tissue,
FIG. 24. Connective tissue in an advancing stage of development. From the umbilical cord.
as it is seen in the umbilical cord of an embryo, is properly an
embryonic or developmental form of connective tissue which is
never found in normal adult life. All the phases of develop-
ment may here be seen, from the most primitive, comprised in
Wharton' s jelly, to the firm, fibrous fascicles that encircle the
Properly speaking, the true mucous tissue is, as its name
implies, a viscid material, and, indeed, is much like half-set
glue, in which the corpuscles are scattered with little or even
The intercellular substance differs from albumen in not con-
taining sulphur ; from chondrin and gelatin, in not being pre-
cipitated by boiling, tannin, or the bichloride of mercury.
THE CONNECTIVE SUBSTANCE GROUP. 65
At an early stage there are no marks of fibrillations in the
intercellular substance, but later fibrils are seen in the vicinity
of the corpuscles, and are some of the early signs that organi-
zation of the tissue is commencing.
The corpuscles at the same time become smaller, and about
the central body or nucleus we see a delicate expansion (Fig.
24 a\ which is the envelope of the connective-tissue corpuscle
a film of great tenuity. Klein believes that in these corpuscles
there are two portions, a granular or firmer part continuous
with the processes, and a delicate expansion that is hardly
visible. It is certain that the connective-tissue corpuscle is
frequently in connection with one or more of its fellows by a
mutual anastomosis of processes. The fibrillation appears to
be at first limited to certain areas about the cellular elements,
so that the long, flattened and pointed lamellae of fibrous tis-
sues on which the corpuscles are attached look like large cor-
puscles with correspondingly large nuclei. Using a earners-
hair brush and pencilling off the specimen under examination,
after soaking in a 10 per cent, watery solution of common salt;
the apparent nuclei with their delicate envelopes are partially
(Fig. 24 1)) or wholly removed. We then see small strips of
more or less fibrillated tissue, having no central body that can
be recognized, even with the use of strong staining solutions.
These and similar observations tend to establish a conviction
that the fibrillated portion arises from the soft, gelatinous ma-
terial by a process of fibrillation inaugurated by the presence
and under the formative action of the connective-tissue cor-
puscle. It is not impossible that the fibrin of the blood, which,
though fluid in the blood-current, is often known to be de-
posited in delicate filaments, may contribute largely, if not
wholly, to the formation of the fibrillse. As the tissue becomes
firmer, the little plates with their anastomosing branches form
a loose network which separates the fibrils into distinctive
bundles or fascicles, and encircles them more or less completely.
There is another view which is offered as an explanation of
the process by which connective tissue becomes organized. It
is this. The change is derived wholly from the corpuscles.
Some of them split up into fibrils, constituting the fibrous
part of the tissue ; the others remain, and are developed into
connective-tissue corpuscles. This view has the support of
00 MANUAL OF HISTOLOGY.
The white corpuscles of the blood are pre-eminently suited
for building tissue. When blood is organized, which occurs
not infrequently, the white corpuscles at once assume an im-
portant role, while the red are soon melted down into a homo-
geneous mass, that is usually absorbed. This change is ob-
served under various pathological conditions.
Fibrous tissue. This substance, which is also known as
fibril] ated connective tissue, is the fully developed material
that has just been described. It occurs either in parallel
FIG. 25. Reticular form of connective tissue. From the human umbilical cord.
bundles or fascicles, in interlacing lamellae, or as a fenestrated
material containing larger or smaller openings. A special va-
riety, the reticular, is seen to great advantage in the umbilical
cord of an infant at birth (Fig. 25).
If a cut be carried through the spongy portions of the cord,
it will be seen that the tissue is composed of bright, shining,
branching bundles, <#, superimposed upon which are a num-
ber of oval, flattened plates, a, at intervals ; about them is
THE CONNECTIVE SUBSTANCE GROUP. 67
a delicate envelope, &, which appears to be highly elastic, so
that it will stretch or relax, according as the networks are
compressed or dilated. By teasing with needles or immersion
for a few days in a 10 per cent, watery solution of common
salt, these corpuscles can often be separated from the bundles,
and then they will be seen to form a connected system. When
entirely isolated from one another, they often appear spindle-
shaped. That this is not their character may be shown by
passing a current of fluid through the specimen a method
already described under the name of irrigation. It is accom-
plished in this way : having affixed small strips of filter-paper
to the edges of the cover on either side, and moistened one side
with fluid, the excess will be absorbed by the other slip, caus-
ing a current by which the corpuscles may be made to roll
over. We then learn that they are disks of an irregularly
flattened form, having longer or shorter processes (c, c, Fig.
25) variations in form which seem to depend, in a great
measure, upon the tension to which they are exposed, and the
position they occupy in the tissue. This explanation will
serve to show why all measurements of such corpuscles are
merely approximative, and have but little value.
They are shrunken by immersion in alcohol, swollen by the
imbibition of water, are drawn out into long, flattened spindles
when the tissue is put on the stretch, or become rounded, per-
haps nearly spherical, during relaxation. They may assume
almost any form as the result of pressure.
The nucleus may be regarded as more of an exception to
this rule ; at any rate it seems that in fresh specimens, when
the substance has been swollen by immersion in water, it is
always oval and flattened.
The bundles upon which these bodies lie are somewhat
cylindrical in form, branched, and composed of separate fila-
ments, that can be separated by Mueller's fluid, or a 10 per
cent, wate^ solution of common salt.
Two other forms of corpuscles may also be noticed : (1) the
kind observed by Waldeyer, and called plasma cells, and
thought by him to be corpuscles peculiarly prone to take up
fat to make fat tissue, bodies four or five times the size of
a lymphoid corpuscle, and rounded in form, containing a cen-
tral body ; and (2) the ordinary lymphoid corpuscles, seen at
times in all tissues.
MANUAL OF HISTOLOGY.
The form of fibrous tissue that occurs in parallel lamellae is
well shown in the mesentery of the frog, and in serous mem
branes generally. No great difficulty will be met with in pre-
paring this tissue, for it is only necessary to remove it from the
frog in the fresh state, acidulate it in a weak (1 per cent.)
watery solution of acetic acid, and mount it in glycerine.
It will be seen that these so-called spindle-cells are really
flattened plates, when viewed flat-wise, and generally irregu-
larly quadrilateral, though the form varies somewhat in each
It is not improbable that some which appear spindle-shaped,
and lie in the interfascicular spaces, have a double office, one
of which is to guard the nutrition of the tissue, and the other
to form a partial lining of a lymphatic channel. The researches
FIG. 26. Connective tissue in the mesentery of the frog.
of Klein tend to establish this double relation, for they show
that these corpuscles lie in the walls of the tymphatic radicles,
which are themselves in direct communication with the perito-
neal cavity by breaks in the endothelial connective-tissue cor-
puscle coating and in actual apposition with the endothelial
elements of the serous membranes.
During the last few years there has been a tendency to regard the serous
membranes, especially such as have large openings and slight reticula, as
having no connective-tissue corpuscles, other than the endothelial, which form,
THE CONNECTIVE SUBSTANCE GliOUP. GO
a covering over them. In the larger trabecles, however, there are connec-
tive-tissue corpuscles, in addition to those just mentioned; they are well
seen in profile, interposed between the bundles (Fig. 26).
Adenoid tissue (Fig. 27). Adenoid tissue is the name given
to the delicate substance that forms the framework of the lym
phatic glands. It consists of fibres in networks which form an
FIG. 27. Adenoid tissue from a human lymphatic gland.
intricate texture, that is filled with the rounded bodies com-
monly known as lymphoid cells. It is exceedingly difficult to
analyze these tissues, because it is not easy to demonstrate any-
thing that conveys to the eye our idea of a cell, i. e., excepting,
of course, the lymphoid corpuscle. The best mode of proced-
ure is the following : Take a lymphatic gland such as the in-
guinal in the early stage of inflammation : harden at first, in
Mueller's fluid, and then in alcohol, and make sections through
On viewing such a specimen under the microscope it will
exhibit a delicate meshwork, packed with lymphoid corpuscles
(Fig. 27, a). Now, if we take such a section and agitate it in a
test-tube with water for a considerable length of time, and then
place it upon a glass slide, pencilling it with a camel' s-hair
70 MANUAL OF HISTOLOGY.
brush, most of the lymphoid cells will be removed, and the
delicate network, c, will be very thoroughly exposed.
It will be seen that, at certain parts of this mesh work, there
are flattened bodies, b, of small size, lying upon the larger
cords of the meshes. It has been held by Klein and other his-
tologists that the reticulum is made of branching corpuscles ;
but this statement must be modified. In some instances the
appearance of netted corpuscles is well seen in those portions
of the glands that are regarded as the lymph passages, where
the adenoid tissue forms the framework of the part. The net-
work seems to be comprised of delicate, silk-like cords, enclos-
ing vast numbers of lymphoid corpuscles, and exhibiting, at
the nodal points of the meshes, flattened corpuscles. These
delicate fibres, however, are often replaced by heavy trabecles,
<?, such as are seen in the figure, and after continual inflamma-
tions the diameter of these latter may be found greater than
that of the spaces.
In these latter instances it is often difficult to find any cor-
puscular elements that may not be separated from the fibres ;
and, indeed, large areas of these fibrous networks may, by dil-
igent pencilling with a camel' s-hair brush, be swept clean of
corpuscles. But neither this rough method, nor agitation in a
test-tube, will always succeed in separating all the corpuscles
from the fibres, even after an immersion in common salt solu-
tion for many weeks. The sum of the whole matter is, that
adenoid tissue does not generally consist of a network of
branching corpuscles, as has been claimed, but rather of a net-
work of fibrous cords, on which the corpuscles are superim-
posed ; they may anastomose, but this point seems difficult to
demonstrate in most cases.
Possibly higher powers than those now in use, or some new
method may solve the question. Where the fibrous networks
have attained some thickness, there is no doubt that we find
the ordinary flattened connective-tissue plates lying on the
bundles and surrounded by a delicate envelope.
Neuroglia (Fig. 28). But a short time since it was not
known positively whether the delicate, supporting substance of
the nervous system, especially of the brain, was granular or
fibrous. Even after Virchow insisted that this substance was
like the other tissues, known as connective, doubt was thrown
upon the matter, for the defining power of most objectives then
THE CONNECTIVE SUBSTANCE GEOUP.
used was insufficient to make out such delicate objects. At
the present time the actual existence of a network is hardly
called in question, for it may be demonstrated with really good
glasses, such as some of the immersion lenses (No. 10) of Hart-
nack's system, and, indeed, by other lenses made both at home
and abroad. As to the question of the corpuscular elements
there is more doubt, and it can hardly be said that their exact
form and shape have been definitely agreed upon by histolo-
gists. We lind, it is true, that where there is a considerable
deposit of connective mate-
rial along the central canal of
the spinal cord, we have the
ordinarjr fibres and corpuscles
already described, and so, too,
near the surface of the con-
volutions. When, however,
we examine the supporting
substances of the white and
gray masses there is less cer-
tainty. The actual condition
may be tolerably well seen
by adopting the following
plan. Place any portion of
the brain or cord a few days
in a weak solution of bichro-
mate of potash (5 per cent.)
or Mueller' s fluid, then immerse it in alcohol until hard ; make
thin sections and stain for twenty -four hours with the follow-
ing solution of hsematoxylin : hsernatoxylini, gr. lij. ; aluminis,
1 j. ; aquse, ? viij. ; mix arid strain.
Wash in distilled water and mount in glycerine, tease with
needles and examine with a high power ; there will then be
little difficulty in seeing that the delicate supporting substance
of both gray and white matter consists of fibres. They may
even be distinctly isolated, for the coloring matter darkens them
somewhat and they become hardened at the same time so as to
be somewhat stiff and unyielding. It will be seen that many
fibrils are disposed in parallel rows which perhaps can hardly
be called bundles, but rather thin laminae ; other similar fibrils
cross them at various angles, giving to the whole, with a
moderately high power, the appearance of a very delicate
FIG. 28. Human brain showing neuroglia.
72 MANUAL OF HISTOLOGY.
meshwork, a. It does not appear as if the fibrillse anastomose
with one another, though this point cannot now be definitely
settled. It must be stated that some of these fibrils are possi-
bly nerve-elements, and yet this is doubtful, because they do
not even seem to be connected with the nerve-fibres ' that are
distinctly shown by this method of preparation.
Granular appearances are always noted in the brain, which
is to be expected when cross-sections are made of the delicate
fibrillse. Three kinds of corpuscles are met with in the brain
and medulla. The first are the variously shaped ganglionic
corpuscles or cells, Fig. 28, &, b, b ; secondly, the ordinary
lymphoid cells, c, c, which are generally seen to have a pale
envelope about them ; lastly, smaller corpuscles, d, d, of irre-
gular sJiapes, and many of them undoubtedly flattened and
appearing to have branching processes. They may be found
in considerable numbers, and can be isolated so that there is no
doubt that they exist.
The fibrillse of the neuroglia do not differ substantially in
size from the fibrillse of fibrous tissues elsewhere.
Tendon-tissue (Fig. 29). Tendon-tissue may be well studied
in the gastrocnemius of the
frog. It is prepared like
the preceding. If, how-
ever, it is desirable to show
the nuclei in adult tissue,
it is well to use nitrate of
silver. Cut a thin section
of a fresh tendon and ex-
pose it for a few minutes
in a per cent, solution
of nitrate of silver, until
the section is turbid or
milky, then place in the
sunlight, and in a few min-
F^.-Tenaon.tl^fco.nthe^. ^ ^ ^^ ^^ ^
give place to dark brown or black, owing to the deposit of
silver, and the tissue may then be mounted in glycerine and
This method will show the corpuscular bodies to advantage.
1 To avoid confusion they are not represented in the drawing.
THE CONNECTIVE SUBSTANCE GROUP. 73
In some cases better results are obtained by the use of chloride
of gold. The method is as follows : Freeze a small portion of
a tendon, then make the thinnest possible section, acidulate it
slightly and immerse in a j- per cent, solution of chloride of
gold until a strong yellow color has been obtained, then soak in
a J per cent, solution of dilute acetic acid and expose to the
sunlight until a purple or reddish color has been obtained.
This will take a variable time, and is not always successful, for
reasons which are not easy to understand.
At considerable distances from one another there will be
seen small dark bodies, which are the corpuscles already de-
scribed. It is difficult to determine whether or not these cor-
puscles are connected together. To isolate them, take a small
piece of young tendon- tissue, immerse three or four days in a
10 per cent, solution of common salt, and then tease. In this
way the cells may be liberated, and they will prove to be irre-
gularly flattened plates.
Sometimes they lie at the intersection of several bundles
and then have separate expansions for each bundle ; the plates
then lie at various angles with one another, and if one be seen
edgewise it looks as if the corpuscle proper were traversed by
Silver or gold, the latter especially, is generally necessary
to show the corpuscles in old tendons. The same method
shows the fibrillated tissue to advantage. The large tendon