in connection with the description of the diseases in which its
occurrence is a constant feature. As the presence of fat in cells is
not necessarily pathological, so an interference with the function of
the cell is not invariably implied by its presence. When its existence
is suggestive of a local destruction of albuminates, a diminution of
cell-activity is a necessary consequence. Such diminished activity
must produce different results as the cells are those of muscles, of
vessels, or of glandular organs.
Even if fat is found in cells under conditions favoring such a
suggestion, it does not follow that the destruction of the cell must
result. Not only is it possible that the fat may be reserved for
eventual oxidation, and its place in the protoplasm be filled by
normal constituents, but it is also possible that the fat may be
eliminated, as such, from the body. The latter event is made apparent
by the experiments of numerous observers referred to by Cohnheim, who
have found free fat in the urine after its introduction into the
venous current.
_Cheesy Metamorphosis, Cheesy Degeneration, Caseation._
Virchow introduced the term cheesy metamorphosis, tyrosis, to
designate the process resulting in the incomplete absorption of pus
and the production of apparently similar changes in certain other
occasional constituents of the body. The characteristic cheesy
appearances were regarded as due to the inspissation of the material
concerned, in consequence of the absorption of its fluid. With this
inspissation there was frequently associated a partial fatty
degeneration, and the cheesy matter represented dead material, which
might undergo further changes, of which softening and calcification
were the more important.
Inflammatory products, as pus and fibrin, were especially prone to
become thus transformed, as well as other relatively transitory
materials of new formation--viz. tubercle and parts of various tumors.
The type of the cheesy metamorphosis was found in the enlarged
lymphatic glands, commonly called scrofulous.
The importance of a clear understanding of the cheesy metamorphosis is
now a matter of history. It is merely necessary to allude to the fact
that these cheesy products were formerly regarded as indicative of the
presence of tubercle, and were the tubercles. Tuberculization and the
cheesy condition were synonymous terms, and their indiscriminate use
led to much confusion with reference to the nature of tubercle.
Quite recently Weigert[32] has called attention to the conditions
present in necrosis resulting from the intermediate stoppage of the
blood-current in a part. The effect is manifested, under favoring
circumstances, by a cheesy appearance of the affected region, to which
the terms decolorized hemorrhagic infarction, anæmic or ischæmic
necrosis, have been applied. {80} Weigert lays stress upon the
existence of a coagulation of the protoplasm of the cells, with an
early disappearance of the nuclei, as the essential feature of this
form of necrosis, the conditions present being regarded as analogous
to those met with in the coagulation of the blood. The term
coagulative necrosis has consequently been introduced by Cohnheim to
represent the process first fully described in detail by Weigert. The
optical and physical properties of the ischæmic or coagulative
necroses of tissue are often manifested as cheesy appearances,
although the term coagulative necrosis includes conditions which do
not present a suggestion of cheese. It is thus apparent that cheesy
appearances may result in two ways: 1, by the inspissation of material
in a state of partial fatty degeneration; 2, by a coagulation of the
constituents of cells whose blood-supply is suddenly and completely
cut off. In the more restricted sense these caseous appearances are
regarded as indicative of a cheesy metamorphosis which arises by the
former of these methods. Cheesy appearances, on the contrary,
dependent upon the sudden death of a part, indicate an ischæmic or
coagulative necrosis.
[Footnote 32: _Virchow's Archiv_, 1880, lxxix. 87.]
Whatever may be the origin of the cheesy condition, the material
presenting this appearance is liable to further changes, known as
softening and calcification. The former event results from the soaking
of the dead part with liquid, in consequence of which a detritus
results. The softening usually begins at the oldest part of the cheesy
mass, and advances toward the periphery. The sanatory evacuation of
the emulsive detritus is permitted when a surface continuous with that
of the external surface of the body is reached, as instanced by the
escape of softened cheesy material from the lungs through a bronchus.
The possibility of the complete removal of the dead mass is thus at
hand, and an eventual obliteration of the resulting cavity may take
place by an adhesive inflammation of its walls.
The complete absorption of the cheesy material of an ischæmic necrosis
may occur by the extension into the latter of a granulation-tissue
from the periphery. Whenever cheesy appearances are found on surfaces,
as the degenerated tubercles of mucous membranes or the circumscribed
necroses in diphtheritic inflammation or in typhoid fever, healing may
be accomplished by their detachment as sloughs, a clean ulcer being
left. Cheesy material is frequently encapsulated--_i.e._ imbedded in a
layer of dense connective tissue, a condition which indicates a local
cessation of the process through which the cheesy appearances arose.
The same may be said of the infiltration of the cheesy mass with
earthy salts--calcification--an event which will again be referred to
in connection with the consideration of the general subject.
_Hyaline Degeneration, Fibrinous Degeneration, Croupous
Metamorphosis._
Certain of the conditions now regarded as indicative of a coagulative
necrosis or a hyaline degeneration were previously described by Wagner
as the result of a croupous or fibrinous metamorphosis. According to
this observer, the cell-contents were transformed, under certain
circumstances, into a substance resembling externally clotted fibrin.
The formation of croupous and diphtheritic membranes, especially of
the larynx, pharynx, and trachea, was thus explained, also the hyaline
casts of the kidney.
{81} The results of this metamorphosis presented a hyaline appearance
under the microscope, and the term hyaline degeneration is now applied
more especially to indicate the production of microscopic changes,
while the hyaline appearances visible to the eye are rather included
under mucous, colloid, or amyloid metamorphoses.
The limitations in the use of the term hyaline degeneration are but
ill defined. On the one hand, there is included the transformation of
muscular tissue, first discovered by Zenker; on the other, the various
changes described by Recklinghausen and others, among which are
embraced the results of Wagner's croupous metamorphosis. As the
hyaline appearances are a frequent result of coagulative necrosis,
these terms are frequently used to indicate the same condition,
according as the optical or etiological features are uppermost in the
mind of the observer.
The hyaline or waxy degeneration of muscular fibre described by Zenker
represents a metamorphosis of the protoplasm of striated muscle in
particular, although the fusiform cells of the muscular coat of the
stomach and intestine may present a similar transformation.
The microscopic appearances are more characteristic than those visible
to the naked eye. To the latter the muscle appears paler, more
translucent, and homogeneous, and proves to be more brittle than
normal. The muscular fibres are found with the microscope to be
swollen, irregular in outline, the myosin transformed into flaky,
glistening masses, without evidence of the normal transverse
striation. These appearances have given rise to the term waxy
degeneration, which suggests a possibility of confusion with the
earlier recognized waxy degeneration of organs, due to the presence of
amyloid material. The waxy transformation of muscular fibre, however,
does not present the reaction with iodine characteristic of amyloid
substance. The degeneration of the muscle is usually regarded as the
result of a coagulation of the myosin, and it is claimed by Cohnheim
that the latter takes place only in dead muscle, either during the
life of the individual or as a post-mortem appearance.
The hyaline degeneration of muscular fibre is found in certain febrile
diseases, as typhoid and typhus fevers, scarlatina, variola, and
cerebro-spinal meningitis. It may also be met with when a muscle has
been exposed to violence, as in the insane who have been placed under
mechanical restraint. It has further been found in the vicinity of
tumors, especially where muscles have been invaded by their growth.
Cohnheim and Weil describe a similar condition in the tongue of frogs
after ligature of the lingual artery.
The pathological importance of the above-mentioned degeneration of
muscle is most prominent in cases of typhoid fever. The occurrence in
this disease of the hæmatoma or blood-tumor of the rectus abdominis is
thus explained, the degenerated muscle and its contained blood-vessels
being ruptured. The muscles of the thigh and the diaphragm frequently
undergo this degeneration; the change is more rarely met with in other
muscles of the body.
Recklinghausen regards a hyaline substance, hyalin, as a normal
constituent of cell-protoplasm which escapes in drops when the cell
dies. Its presence indicates a diminution in the vitality of the cell
from various causes. Under the microscope it appears as a sharply
defined, highly refractive meshwork, enclosing spaces of irregular
shape and size, in {82} which are frequently found nuclei, more rarely
cells or granules. Langhans has described this appearance as
channelled fibrin. It has been met with in the placenta, diphtheritic
membranes, blood-vessels, tubercles, and gummata.
The latest contribution to the history and nature of this form of
degeneration has been furnished by Vallat,[33] from whose article many
of the above data have been obtained.
[Footnote 33: _Virchow's Archiv_, 1882, lxxxix. 193.]
_Mucous Degeneration, Mucous Metamorphosis, Mucous Softening._
Of the various degenerations presenting a colloid--_i.e._
gelatinous--condition, the mucous variety is one of the most striking.
Its gross appearances may not differ materially from those to be
described under the head of colloid degeneration, but the diagnostic
characteristic of the change is to be found in the presence of mucin.
The presence of this substance is readily detected by the addition of
acetic acid to mucus, the effect being a fibrillated appearance of the
latter, the fibres presenting a more or less parallel distribution.
This fibrillation of mucus is regarded as the result of a coagulation
of its mucin, previously held in solution by an alkali. Mucin is thus
present in the body as a normal constituent, and, in the secretions
from mucous membranes, owes its origin to the existence of epithelial
cells, whether these represent gland-cells, as in the case of the
muciparous glands of the bronchial mucous membranes, or whether they
are superficial cells, as those of the gastric and intestinal mucous
membranes.
In the origin of mucus as a secretion from glands Heidenhain[34]
claims that a destruction of gland-cells accompanies the continuance
of the secretion. At the outset, however, the mucin escapes from the
cells, the latter remaining relatively intact. With the persistence of
the secretion there results a destruction and a new formation of the
muciparous cells. In the pathological production of mucus from mucous
membranes, as in catarrh, there is no reason to doubt that the
persistence of an irritation is the cause of abundant mucus, and that
the latter is dependent upon the rapid formation and destruction of
epithelial cells.
[Footnote 34: _Hermann's Handbuch der Physiologie_, 1880, v. 64.]
The origin of mucus from epithelial cells under physiological and
pathological conditions being apparent, it readily follows that the
epithelioid cells of tumors might be supposed to be liable to a
similar metamorphosis. It is well known that cancerous tumors,
especially those of the stomach and large intestine, are frequently
met with, which present an abundant gelatinous material, more or less
completely filling the spongy, fibrous meshwork. These are the
alveolar, gelatinous, or colloid cancers.
The gelatinous or colloid material often gives the reaction of mucin,
and the microscopic appearances of the tumor show that the jelly-like
substance lies in that part of the tumor which corresponds with the
position of the epithelioid cells. The latter are found in various
stages of degeneration, the appearances being similar to those
observed in the mucous degeneration of true epithelium.
The prevailing theory of the origin of cancer from epithelial
structures {83} readily suggests an explanation for the frequency of
the mucous variety of cancer in connection with those parts from which
mucus normally arises from the degeneration of the epithelium.
The mucous metamorphosis affects connective tissues as well as
epithelium. The Whartonian jelly of the umbilical cord and the
vitreous humor of the eye are known, through the investigations of
Virchow, to owe their gelatinous condition to the presence of mucin.
The latter lies in the intercellular substance; that is, between the
cells. The appearance of these indicates no degenerative process, but
the presence of mucin is obviously an essential constituent of the
tissue. Whether this mucin represents a transformation of the gelatin
of the intercellular substance, or a secretion from the fixed cells,
or a metamorphosis of the migratory cells of the tissue, is not known.
In mucous tissue, however, there is present mucin, wholly independent
of any epithelial degeneration. Mucous tissue is present in the eye as
a normal constituent of the adult, and in the umbilical cord as a
normal constituent of the infant at full term. It is also abundantly
met with in the subcutaneous and intermuscular tissues of the foetus.
Its pathological occurrence in the adult as a circumscribed tumor, the
myxoma, may also be mentioned.
A gelatinous substance containing mucin is found in the adult
independent of the mucous tissue, but obviously arising from a
transformation of intercellular substance. The most striking example
of this occurrence is the cystoid softening of cartilage, especially
of the costal cartilages of old people, the basis substance being
transformed into a fluid containing mucin. A similar metamorphosis is
of frequent occurrence in the intervertebral disks and in the
destruction of cartilage in acute and chronic inflammations of the
joints. The intercellular substance of cartilaginous tumors also
becomes softened and converted into a liquid containing mucin.
In osteomalacia and in the absorption of bone the mucous degeneration
of the bone-cartilage plays an important part. The lime salts are
first set free, and the cartilage then undergoes a mucous
degeneration; the product is either absorbed or remains as a liquid
within cavities of large or small size. The mucous metamorphoses of
fibrous and fat-tissues, likewise of bone-marrow, are well recognized
instances of the occurrence of a mucous transformation of the
intercellular substance of connective tissues. Finally, clotted
fibrin, so often met with as the product of the inflammation of serous
surfaces, may undergo a mucous metamorphosis, and, thus transformed,
offer a suitable material for absorption.
_Colloid Degeneration, Colloid Metamorphosis._
Laennec used the term colloid in a descriptive sense to indicate a
gelatinous appearance, and for a long time its use was thus
restricted. As the colloid appearances were found to differ in their
chemical reaction, their distribution, and their pathological
importance, and as the term was further extended to include
appearances seen with the microscope, it obviously became necessary to
subdivide the colloid series of changes according to the observed
differences. Its use is now limited to those gelatinous conditions or
appearances due to the presence of a fixed albuminate, homogeneous or
finely granular, translucent, colorless or pale {84} yellow, of
varying consistency, which does not become fibrillated on the addition
of acetic acid, and which does not change in color when acted upon by
iodine. This albuminate is considered in most instances to represent
the result of a transformation, a metamorphosis of cells, and is
associated with an impairment of their function--a degeneration which
is progressive, and leads, sometimes, to the destruction of the organ,
as occurs in certain instances of colloid degeneration of the thyroid
body. Usually, the process is limited, affecting particular parts
rather than the whole of an organ. The reaction presented by a
solution of sodium albuminate in the presence of neutral salts leads
to the view that colloid material may represent a coagulation of an
albuminous substance or substances under favoring conditions. The
presence of colloid masses in the kidney thus meets with a plausible
explanation.
The place of its typical occurrence is the thyroid body in certain
cases of goitre, and it is early met with as a homogeneous substance
replacing the granular cell-protoplasm. With its increase the latter
disappears, and the entire cell is transformed into a homogeneous
sphere. At times the colloid substance may be seen to project from the
surface of the cell as a pale rounded clump. The aggregation of these
clumps results in the presence of masses of various size, in which may
be found granules of fat or pigment and crystals of cholesterin, which
are accidental, not essential. Colloid masses are sometimes met
with--in lymphatic glands, for instance--as concretions, mulberry-like
aggregations of stratified colloid bodies, which may be infiltrated
with earthy salts. Colloid material may eventually become liquefied,
transformed into a sodium albuminate; and the presence of cysts in
certain varieties of goitre is thus explained. The coexistence in the
kidney of colloid accumulations and watery cysts has led to the view
that the latter may, under certain circumstances, result from the
former through the liquefaction of the colloid material. The same view
is held with regard to the origin of cysts frequently met with in the
choroid plexuses.
The colloid metamorphosis of cells is also to be found in the
epithelium of mucous membranes and their glands, in the prostate,
suprarenal capsule, sebaceous glands of the skin, and in the cells of
certain tumors.
_Amyloid Degeneration, Amyloid Infiltration, Waxy Degeneration,
Lardaceous Degeneration._
The colloid appearances due to the amyloid degeneration of cells are
of the greatest clinical importance from their frequent occurrence and
the gravity of the symptoms connected with their presence. In amyloid
degeneration there is the transformation of the cell-protoplasm into
an albuminous material different from other albuminates found in the
body. This transformation is at the expense of the functional activity
of the cell, and the latter becomes inert. Amyloid degeneration
represents no mere substitution, but an addition, since the affected
tissue is increased in volume. The albuminate was called amyloid by
Virchow in consequence of its color-reaction with iodine. Its method
of origin is wholly unknown, never being found in the circulating
fluids nor in articles of food. It is met with chiefly in the cell,
although its presence in the intercellular substance of old people is
recognized, and its occurrence in {85} the midst of the thrombotic
deposition on inflamed valves and in the results of inflammatory
processes is also recorded.
At present the question is under discussion whether the amyloid
degeneration may affect cells of the most varied character, or whether
it is limited to those of connective tissues. Eberth[35] maintains
that in all cases the amyloid disturbance is seated in the connective
tissue. Kyber,[36] the latest investigator, in opposition to this view
maintains that this affection is not limited to the connective tissue,
but may also be seated in the parenchymatous cells of organs. Whether
the one of these views is to exclude the other, or whether both are
not correct, remains for future investigation to decide.
[Footnote 35: _Virchow's Archiv_, 1880, lxxx. 138; 1881, lxxxiv.]
[Footnote 36: _Ibid._, 1880, lxxxi. 7, 111.]
Wherever the amyloid material may be situated, the result is a
transformation of the cells into a homogeneous, glistening, colorless
material, which occupies more space than the original cell, and, when
abundant, is accompanied with a loss of the primitive details of the
cell-structure. This material is recognized by the color it presents
when acted upon by iodine alone, by iodine and sulphuric acid, or by
methyl-aniline. The first produces a reddish-brown color, the second a
blue, and the last a violet or purple color. These reactions are all
characteristic, and the first is of special value in the macroscopic
recognition of the process, while the last two are of special
importance in the microscopic recognition of the earlier stages of the
affection.
With the advance of the degeneration and its dissemination, the organ
affected presents, in the diseased portions, pale-gray, glistening,
translucent patches, and becomes increased in size and density in
proportion to the quantity of amyloid material present. The change
appears primarily in the vessel wall or outside the same, and there
results a diminution in the calibre of the vessels, with a lessened
quantity of blood in the organ.
From the homogeneous and translucent appearance of the surface and the
increased density of the tissues the resemblance to bacon or wax is
suggested, and the terms lardaceous, bacony, or waxy degeneration have
been applied. Notable differences in degree and seat occur in
connection with the organs diseased. In the spleen, for example, the
change may be limited to the arteries of the Malpighian bodies and
their immediate surroundings. To this condition the term sago spleen
is applied, the enlarged, rounded, translucent, and projecting bodies
suggesting granules of boiled sago. The appearances of the diseased
part are further affected by the association of other conditions, as
the presence of fat or pigment. When fat is present, it is often to be
regarded as a result of the gradual and progressive increase in the
obstruction to the circulation of blood in the organ.