{72} importance, is oedema of the lungs, often taking place toward the
end of life, at times quite suddenly. This form has usually been
attributed to increased transudation from arterial congestion or
venous stagnation. The former view is directly refuted by the
experiments of Welch,[28] who offers the explanation now accepted.
With the obliteration of three-fourths of the arterial supply to the
lungs of the animals experimented upon, no oedema resulted from the
assumed collateral fluxion into the branches of the pulmonary artery
which were left open. The obliteration of the same area of venous
distribution was necessary before the occurrence of oedema. Oedema of
the lungs was further found to result from a ligature of the aorta
near the heart. The comparative frequency of oedema of the lungs in
man, and the rarity of such extreme mechanical disturbances as those
produced experimentally, led Welch to paralyze the left ventricle. The
conditions as regards the pulmonary circulation then corresponded with
those mentioned as causes for oedema from venous obstruction. The
continued action of the right ventricle forced blood into the
pulmonary capillaries, where it was compelled to accumulate in
consequence of the inability of the left ventricle to receive and
expel it. Welch consequently regards the immediate cause of this form
of pulmonary oedema as a predominant weakness of the left ventricle. A
weak heart does not suffice for the production of the oedema, since
this condition is not found when both ventricles are alike enfeebled.
[Footnote 28: _Virchow's Archiv_, 1878, lxxii. 375.]
Degenerations.
The degenerations represent disturbances in the nutrition of the
tissues of the body, in consequence of which their functions become
impaired, if not destroyed. The latter result obviously attends the
death of cells, which may occur in the course of the degeneration. The
processes concerned are called necrobiotic by Virchow, as they
represent vital processes leading to death. Although in many of them
the cell is decaying during their continuance, its recovery is
possible with the disappearance of the conditions which have
transformed physiological into pathological processes. The
degenerations affect intercellular substance as well as cells, and are
called metamorphoses, infiltrations, or degenerations, as a
transformation of normal into abnormal material, or the addition of
extraneous substances, or the functional impairment of the part
assumes the greatest prominence.
_Cloudy Swelling, Albuminoid Infiltration, Granular Degeneration,
Parenchymatous Degeneration._
Of the various modifications in the appearance of cells under
pathological conditions, there is none, perhaps, more commonly met
with than that known by the above terms. A granular appearance may be
regarded as an essential characteristic of protoplasm, and is an
attribute of cells of epithelial origin as well as of those which
belong to other groups of tissues. The abundance of granules present
in a normal cell depends largely upon its shape, size, and situation.
These granules present various {73} relations to chemical agents, some
being soluble in alcohol and ether, others in acids and alkalies, and
many of them, especially those met with in the form of degeneration
now being considered, show from the various reactions that they are of
the nature of albumen. Since their exact composition, in all
instances, is undetermined, they are called albuminoid, and when in
excess the cell is considered to be infiltrated with these granules,
and the organ presents the appearances regarded as characteristic of
an albuminoid infiltration. A granular cell becomes much more granular
when it is thus infiltrated, and it is therefore a matter of
difficulty to recognize from the appearance of certain single cells,
as those of the liver or kidney, whether or not the number of granules
present is abnormally increased. When, however, a large number of
cells of any given organ contain more than the normal quantity of
these albuminoid granules, the appearance of the organ becomes
modified. In extreme cases the latter is swollen, doughy in
consistency, with ill-defined structural details, and in all instances
presents an opaque appearance. The term cloudy swelling is thus purely
descriptive, and was applied by Virchow to designate the optical
appearances of the condition in question. The granules, which
disappear on the addition of acids and alkalies, are apparently either
added to the cell or result from a precipitation within the same.
Frequently associated with these albuminoid granules are others,
distinctly recognizable as globules of fat. An apparent increase of
nuclei is often observed, and in certain organs, as the kidneys, the
cells seem less coherent than is normally the case. The study of this
condition in the kidneys is further of interest as indicating that the
border-line between a parenchymatous degeneration and a parenchymatous
inflammation is purely arbitrary. From similar exciting causes there
may be associated, with the described alterations of the epithelial
lining of the tubes, the exudation of albumen, the formation of casts,
the desquamation of epithelium, and the presence of leucocytes within
the tubules.
When the macroscopic changes are of moderate degree, and the
disturbance of function relatively slight, while the concurrent
alterations elsewhere, from the simultaneous action of the same cause,
are predominant and characteristic of the disease, the condition is
conveniently regarded as a degeneration occurring in the course of the
latter, rather than an inflammation. The latter term, on the contrary,
is to be applied when the granular infiltration of the cells is
associated with other evidences of an inflammatory exudation, and when
the pathological disturbances are to be directly attributed to the
parenchymatous changes.
It is customary to speak of cloudy swelling as a nutritive change, and
the condition may be induced by those causes which interfere with the
nutrition of parts or of the whole of an organ. Many authorities
regard this granular or parenchymatous degeneration as closely allied
to fatty degeneration, since many of the causes which produce the one
occasion the other. The former is often spoken of as an earlier stage
of the latter, from the frequent association of the albuminoid
granules with numerous globules of fat as a result of the more
prolonged or more intense action of a given cause.
Organs which give evidence of a granular degeneration contain, as a
rule, a diminished quantity of blood. This feature is usually
attributed to the pressure of the swollen cells upon capillary
blood-vessels. The {74} anæmic organ obviously becomes still more
cloudy, gray, and opaque in appearance from the diminished quantity or
impoverished quality of the blood.
The granular degenerations of the heart, liver, and kidneys, as a
whole, usually occur simultaneously, and afford a most important means
for the post-mortem recognition of the infective diseases. The
condition is therefore to be looked for in the exanthemata, especially
in small-pox and scarlet fever, also in erysipelas, septicæmia in its
manifold forms, diphtheria, typhoid and typhus fevers, cerebro-spinal
meningitis, etc. A common feature in all these cases is the occurrence
of fever, and it has been claimed that this element is the cause of
the degeneration. In opposition to this view is the well-known fact of
its presence in afebrile cases of poisoning from carbonic oxide, and
its absence in certain cases of pneumonia and exposure to high
temperatures.
The universal occurrence of cloudy swelling in fatal cases of the
affections above mentioned leads to the inference of its presence in
those instances terminating in recovery without obvious permanent
impairment of the organs and tissues concerned. It is therefore agreed
that the process may terminate in resolution--_i.e._ in a
disappearance of the excess of granular material. On the other hand,
its association, under circumstances, with fatty degeneration suggests
as extremely probable that the latter condition may represent a result
of the albuminoid infiltration. Even if this more serious issue
exists, the possibilities are still at hand for an absorption of the
degenerated material and a restitution of the destroyed protoplasm.
The effect upon the individual is evidently determined by the
persistence and dissemination of the condition, which, in turn, are
controlled by the immediate cause and the peculiarities of the
individual acted upon.
_Fatty Metamorphosis, Fatty Degeneration, and Fatty Infiltration._
The fat which is present within the body under physiological
conditions owes its origin primarily to the food taken. A diet which
is abundantly fatty furnishes a direct source for much of the fat
which appears accumulated in the various organs and tissues. Although
it may now appear that such a statement needs but little confirmation,
it is not long since the opinion prevailed that nearly all the fat in
the body came from the hydrocarbons of the food. This seemed all the
more plausible as the herbivora readily accumulated fat, although
their diet might contain this element in very small quantities.
Hofmann[29] made a decisive experiment with reference to the origin of
fat from fatty food by feeding a dog, made lean by starvation, with
bacon in abundance, but with little meat. In the course of a few days
the greater part of the fat introduced was deposited within the
tissues of the animal. Other experimenters have arrived at a similar
result, and it can no longer be questioned that fat, accumulated
within the body, owes its origin chiefly to the absorption of fat from
the food taken.
[Footnote 29: _Zeitschrift für Biologie_, 1872, viii. 153.]
Another source for the fat of the body has long been
suggested--namely, the albuminates of the food. In the admirable
article on the formation of fat by Voit,[30] from which most of the
information herein {75} presented is derived, it is claimed that he
and Pettenkofer were the first to prove the origin of fat in the body,
under normal conditions, from albumen. This proof was an inference,
however, although presenting a high degree of probability. Valuable
evidence in the same direction was furnished by Kemmerich, who found
that the milk of a cow during a certain period held more fat than was
contained in the food; Subbotin and Voit have shown that more milk is
secreted the richer the diet in albumen. Still other observers have
furnished more decisive proof that fat is formed from albuminates.
[Footnote 30: _Hermann's Handbuch der Physiologie_, 1881, vi. 1, 235.]
Two sources for fat in the body under physiological conditions are
thus recognized: 1, the free fat in the food; 2, the fat derived from
the decomposition of the albuminates of the food.
Voit admits the possibility of the hydrocarbons serving as a third
source, although this possibility is unnecessary in most cases. Should
instances arise, however, where other sources for fat are found
insufficient, the hydrocarbons must be regarded as filling the gap.
Fat which is taken into the body is considered to be either consumed
or stored. That which is stored is chiefly accumulated in the great
reservoirs--viz. the subcutaneous and perinephritic fat tissue, the
mesentery, omentum, and bone-marrow--although it may be found
elsewhere, in the fluids and tissues of the body. This accumulation
serves as a source to be drawn from in case of need, and is called
upon where the easily-decomposed soluble albumen is disposed of by the
functional activity of the cells. An acting muscle demands food for
its work, and consumes first the soluble albumen, then the fat. An
excessive waste of fat is delayed by the decomposition of
hydrocarbons, but the demands may become so great that albumen, fat,
and hydrocarbons are consumed more rapidly and constantly than they
can be supplied. It being, therefore, admitted that fat is formed from
the albuminates, as well as from the fat of the food, the question
readily presents itself whether fat may not be formed from the fixed
albuminates of the body, especially from those contained within its
cells.
It is well known that in the secretion of sebum the superficial cells
of the sebaceous follicles contain fat in great quantity, while the
deeper layers are comparatively free from any appearances indicative
of the presence of fat. It is further admitted that when pus is
retained for a time the individual corpuscles contain fat-drops in
quantity and become transformed into fatty granular corpuscles.
Eventually, the pus is transformed into a detritus in which fat-drops
are found in great number.
Similar appearances may be present in the protoplasm of muscular
tissue, the cells of the liver, kidneys, and gastric glands, when
poisonous doses of phosphorus or arsenic are given. The occurrence of
an acute fatty metamorphosis of the cells of various organs in
new-born children has repeatedly been observed. The presence of fat in
various organs of the body in pernicious anæmia, and in the heart in
connection with stenosis of the coronary artery, is universally
recognized. The abuse of alcohol, long-continued obstruction to the
flow of venous blood, exposure to high temperatures, are all known to
be conditions in connection with which fat-drops are found in the
various cells of the body. The effects of poisoning with phosphorus
and arsenic are of special importance, as showing that the abundance
of fat present in the cells represents a result of the degeneration of
these cells, {76} since it takes place when the animal is deprived of
food. Although there is an evident destruction of albumen, there is
also a diminished elimination of carbonic acid and admission of
oxygen. These facts are explicable on the ground that the fat present
is not consumed, and the accumulation in the cells is evidence of this
lack of consumption. The fat is not simply stored, as none is taken
in, nor is any food received from which fat might be formed. Its
presence, therefore, must be regarded as due to degeneration.
Since fat may be formed in the body as a result of the metamorphosis
of cell-protoplasm, it is desirable to ascertain whether there are any
means by which stored fat may be distinguished from that present as
the result of a degeneration of the cell. The term fatty infiltration
has been used to indicate the presence of stored fat, the latter being
regarded as simply taken into the cell and retained for a longer or
shorter time, without any necessary interference with other functions
possessed by the cell.
In fatty degeneration, on the contrary, it is considered that the
quantity of fat present indicates a corresponding diminution in the
albuminates of the cell, and is connected with a diminution in the
function of the latter, all the greater the more abundant the fat.
It is found that in fatty infiltration, as a rule, the fat is present
in large drops, the size of the cell being increased in proportion to
the quantity of fat present. Although there may be several drops
present, they tend to run together, as is suggested by their different
size, varying proximity, and the constant presence of a considerable
quantity of protoplasm. In organs, on the contrary, whose function is
seriously, even fatally, impaired, the fat, as a rule, assumes rather
a granular form. Many minute fat-drops are present, and the cell is
not particularly, if at all, increased in size. The more abundant the
fat the less the protoplasm. Appearances are met with indicating a
transition between cells with few fat-granules and those with many.
If the morphological appearances of fatty infiltration and of fatty
degeneration were constant, there would obviously be little or no
difficulty in determining the nature of the process manifested by the
presence of fat. The exceptions occur both in fatty infiltration and
fatty degeneration. In the cells of the liver of an animal poisoned
with phosphorus fat makes its appearance in large drops, while in the
heart and kidneys of the same animal the fat is present in a granular
form.
During absorption from the intestine in the process of digestion fat
is present in the epithelium in a finely granular form. When digestion
is completed fat is no longer met with in these cells. The presence of
large or small drops, therefore, cannot be regarded as a sufficient
test of the origin of the fat. It is of equal, if not greater,
importance to bear in mind the organ concerned.
In the heart, liver, kidneys, and gastric glands, as well as
elsewhere, with the exception, perhaps, of the mammary gland, the
presence of many small fat-drops in the cells indicates a degeneration
of its protoplasm. The presence of large fat-drops, on the contrary,
in the organs and tissues, with the exception of the liver, indicates
an infiltration. Large fat-drops, then, may be present in the cells of
the liver as the result of an infiltration or of a degeneration. In
order to form a satisfactory opinion of the {77} nature of the
appearances in the liver in doubtful cases, it is important to note
the condition of those organs which may be simultaneously in a state
of fatty degeneration.
The accumulation of fat under physiological conditions is obviously
brought about, on the one hand, by those causes which permit a free
introduction, absorption, and deposition, and, on the other, by those
which check its oxidation or elimination with the secretions of the
body, as the bile, in which it may be present to a considerable
extent. A diet rich in fat, or in albuminates readily converted into
fat, offers a favorable element for the absorption of fat by the
healthy individual. If the organism demands but little of this fat for
oxidation, as in the case of the sedentary person, an accumulation is
likely to occur. This may become so considerable that obesity results.
Tissues in which normally but little fat is accumulated may become
infiltrated to a large extent. The intermuscular fibrous tissue thus
becomes loaded, and the activity, as well as the nutrition, of the
muscles is impaired. This accumulation may be manifested not only in
the voluntary muscles, but in the heart as well, which may present
abundant sub-pericardial and sub-endocardial fat, the myocardium also
being interlarded with streaks of fat, the so-called fatty
infiltration of the heart. The abdominal walls may become thickened to
the extent of a couple of inches, and the mesentery, omentum,
perinephritic tissue, and liver may become enormously increased in
weight from the mass of accumulated fat.
This infiltration of fat may take place under pathological as well as
physiological conditions. It is apparent that those causes which check
oxidation are likely also to prevent the consumption of fat, and it is
well known that the destructive processes in the lung, grouped under
the term pulmonary consumption, accomplish this result. Something
more, however, is necessary than the obliteration of pulmonary
blood-vessels and the destruction of an aërating surface. There may
be, as in emphysema of the lung, a diminished respiratory and vascular
surface, yet evidences of fatty infiltration, particularly of the
liver, are wanting. It seems probable that the constant anæmia, with
the loss of the blood-corpuscles, of pulmonary phthisis is an
important additional factor in checking oxidation in this disease.
This factor, it is needless to say, is not a necessary occurrence in
pulmonary emphysema.
Litten[31] has shown that when certain animals are exposed to high
temperatures the appearances of fatty infiltration and degeneration
are present in various organs of the body. He attributes the fatty
degeneration to a direct poisoning of the red blood-corpuscles and a
resulting diminution of the oxidizing processes.
[Footnote 31: _Virchow's Archiv_, 1877, lxx. 10.]
It is universally admitted that in chronic alcoholism a fatty liver is
frequently met with, even in the absence of those chronic interstitial
tissue-changes usually characterized under the name cirrhosis. Alcohol
is known to check the reception of oxygen and the elimination of
carbonic acid, and, whatever other disturbance of cell-activity it may
produce, its effect in favoring the accumulation of fat is directly
attributable, in part at least, to this disturbance of oxidation.
In those conditions known as cachexiæ, the constant accompaniment of
progressive and wasting diseases, as cancer, leucæmia, chronic
dysentery, {78} etc., a fatty infiltration, particularly of the liver,
is a frequent accompaniment. A cachexia is dependent upon a complex
series of processes, many of which tend to check oxidation, and in
this respect is to be grouped with the conditions previously
mentioned. That the associated fatty infiltration is intimately
connected with the deficient oxidation is not to be doubted, although
the agents producing this deficiency may vary in detail.
The causes which favor fatty degeneration are numerous, and the result
represents one of the most serious conditions which can affect an
organ. As oxidation represents the chief means of normally disposing
of fat, so, pathologically, deficient oxidation favors the retention
of fat due to degeneration. Were a constant renewal of protoplasm to
take place, the degenerated fat might be displaced into the
circulation or retained within the cell. If the latter event should
occur, the result would be apparent as an infiltration, owing to the
increased size of the cell, although the condition giving rise to the
presence of the fat is a degenerative process. The importance of
impairment of nutrition as the chief cause for fatty degeneration is
thus obvious. It may readily be produced, experimentally, by measures
which check the flow of blood to a part. The same measures necessarily
prevent the presence of abundant oxygen, as fewer red blood-corpuscles
are presented.
Fatty degeneration resulting from impaired nutrition is apparent in
the heart in consequence of stenosis of its coronary arteries, in the
kidneys as a result of interstitial processes obstructing the
capillary circulation, in the brain from obliterative processes in the
arteries at the base or within the organ, and in blood-vessels from
the effect of age.
The cause of fatty degeneration may be general as well as local. In
poisoning from phosphorus and arsenic the appearances in most of the
organs indicate an actual destruction of protoplasm. Analysis of the
secretions confirms this inference, as the production of urea is
largely increased. Furthermore, there is less oxygen taken in and less
carbonic acid eliminated. As has been previously stated, these
conditions may be present in the starving animal. The fatty
degeneration is thus easily explained as a metamorphosis of
cell-protoplasm, and the deficient oxidation of the fat calls direct
attention to its accumulation rather than elimination.
In acute yellow atrophy of the liver and in cases of severe jaundice
fatty degenerations are constantly met with. That the origin and
accumulation of fat in these affections is also due to rapid
tissue-metamorphosis and checked oxidation is highly probable.
Although the elimination of urea diminishes rather than increases, as
shown by Schultzen and Riess, there are other links in the chain of
retrograde changes, as the appearance of leucin and tyrosin,
indicative of the extensive destruction of albuminates.
It is unnecessary in a work of the present character to call attention
to all the possible circumstances under which fat is present in the
body as the result of degeneration. Mention may be made of the acute
parenchymatous (fatty) degeneration of new-born children, of the
results of excessive bleeding, and of pernicious anæmia otherwise
occasioned. The fatty degeneration of the uterus after parturition, of
paralyzed muscles, and of tumors, the atrophic fatty degeneration of
the liver in chronic {79} passive congestion (nutmeg liver), are all
well-known examples. To these may be added the fatty degenerations
associated with amyloid and interstitial processes. It is apparent
that in most of these instances the common features of rapid
tissue-metamorphosis and deficient oxidation are present, and, being
present, offer a ready explanation for the appearance of the fat.