discolorations which are unquestionably due to the metamorphosis of
the coloring matter of the blood. Examples are furnished not only by
the extravasation of blood on a large scale, but also by the escape of
red blood-corpuscles in small numbers. Such an escape takes place from
the pulmonary vessels in chronic obstruction to the admission of blood
into the left side of the heart. The resulting brown induration of the
lungs owes its color to the metamorphosed blood-pigment which is
present as hæmatoidin in the interstitial tissue of the lungs, as well
as contained within amoeboid cells in the alveolar and bronchial
cavities.
It is probable that a similar transformation of hæmoglobin takes place
in the spleen and elsewhere in melanæmia. In this condition the black
granules of pigment, although differing in color and form from
hæmatoidin, contain iron, and have received the name melanin. These
granules are either free in the blood or are contained within the
white {93} blood-corpuscles. Their origin in the spleen is directly
suggested by their frequent presence, often in considerable numbers,
in the large, so-called splenic, corpuscles of the blood in the
hepatic capillaries. Eventually, the pigment is found at more remote
points in the circulation, and becomes fixed in the interstitial
tissue of the various organs of the body.
The black pigment of the cells of melanotic tumors, also called
melanin, is not to be directly traced to the hæmoglobin. Virchow[45]
early called attention to the absence of iron in such pigment.
Ferrated and non-ferrated varieties of melanin are thus to be
recognized, the term being used in the same way as hæmatoidin,
indicative of a microscopical appearance. A still further complication
in the composition of melanin is suggested by Kunkel,[46] who has
isolated a ferrated pigment from melanotic tumors. It shows, however,
with the spectroscope, no relation to hæmatin, bilirubin, or
hydrobilirubin. That its nature is similar to the normal pigment of
the skin and choroid is suggested by the customary origin of the
melanotic tumors in such pigmented tissues, and by the resemblance in
appearance and reactions.
[Footnote 45: _Virchow's Archiv_, 1847, i. 378.]
[Footnote 46: Ziegler, _op. cit._, 100.]
That pigment of the most varied sort may be introduced into the body
from without, and may remain indefinitely in the organism, is
sufficiently well known from the results of tattooing. What is
essential in such cases is, that the pigment shall be finely divided
and insoluble in the fluids of the body. The most important of such
pigmentations are those taking place through inhalation into the
lungs. The reception by this channel of particles of soot is so common
that it is most exceptional for the lungs of an adult to be free from
the bluish-black discoloration due to this agent. Particles of
coal-dust presenting the details of vegetable structure are met with
in the lungs of individuals exposed to an atmosphere charged with this
material. The worker compelled to inhale the dust of iron eventually
accumulates a store of this substance, the quantity of which is
essentially dependent upon the length of exposure, the degree of
impregnation of the atmosphere, and the insufficient nature of the
protectives employed.
Although a large part of the pigmentation under such circumstances is
due to the direct presence of the foreign body, the appearances are
also partly the result of consequent minute hemorrhages. The coal-dust
and the iron-filings are often sharp and jagged fragments, which
penetrate the delicate tissues, and the escaping red blood-corpuscles
are acted upon by the amoeboid cells in the air-passages, with the
consequent formation of hæmatin or hæmatoidin, as are the
blood-corpuscles in larger hemorrhages. The inhaled pigment finds its
way, either directly or by the agency of amoeboid cells, into the
lymphatics and fibrous tissue of the lungs, and remains indefinitely
either in the bronchial and pulmonary lymphatic glands or in the
interstitial tissue of the lungs.
Attention may be here called to that pigmentation of the skin and
deeper-seated parts of the body, especially of the kidneys, known by
the term argyria. The long continued internal use of nitrate of
silver, in former years so extensively employed, especially in
diseases of the nervous system, results in the reduction of the silver
and its deposition as minute particles in the tissues. Whether the
silver is first reduced in the {94} intestine and then absorbed, or
whether it is absorbed as an albuminate and subsequently reduced,
still remains an open question.
Although the pathological pigmentations form an extended series of
alterations, the clinical importance of the condition may be regarded
in many instances as trivial. The pigments resulting from
extravasation produce no disturbance of function. The presence of
bile-pigment does not account for the symptoms of jaundice. The
clinical importance of melanæmia has perhaps been overrated. The
earlier observations led directly to the inference that mechanical
obstruction to the circulation in various organs might take place. The
particles of pigment and the cells containing them were so numerous
that this inference seemed quite probable. The evidence is still
lacking, however, which proves the existence of definite symptoms and
characteristic lesions as the result of the melanæmic condition.
The inhaled foreign bodies, as coal and iron, are productive of
greater disturbances, and are well known as efficient causes in the
production of chronic pulmonary consumption. The coal-miner's and
scissors-grinder's phthises usually have, as an anatomical basis,
catarrhal conditions of the aërating surfaces and interstitial
inflammations of the pulmonary connective tissue. Mechanical
obstruction to the aëration of the blood may also be present from the
extreme quantity of the foreign material in the lungs.
Tuberculosis.
Until the investigations and discoveries of the past few years, the
presence of tubercles in the various organs and tissues of the body
had been regarded as the essential element of tuberculosis. The
evidence to be presented in the following pages will show that the
immediate cause of tubercles may produce other lesions as well, and
that the presence of a specific virus as the efficient cause of
whatever may be the lesion, rather than the existence of tubercles, is
to be regarded as the characteristic feature of the disease
tuberculosis.
The tendency of the present is to regard the latter term as including
the various morbid processes connected with the origin, presence, and
growth of a specific, organized virus, their dissemination,
metamorphoses, and effects. Whether all those processes in connection
with which the virus is found are due to the latter, or whether some
may not arise and exist independently of the same, are among the
questions whose answer is remote rather than at hand.
As the presence of the cause of tuberculosis is the test demanded by
some authorities for the existence of the process, so the anatomical
classification has depended upon the existence of the tubercle. The
substitution of tubercle for organized virus in the general definition
of tuberculosis represents the distinction between the anatomical and
the etiological classification of this affection.
A tubercle was originally a small rounded body, a little tuberosity,
and at the close of the last century the specific tubercle was
distinguished from other rounded nodules.
Till the discovery of Villemin, the recognition of the tubercle was
{95} essentially based upon its anatomical characteristics. Previous
to the studies of Reinhardt and Virchow these related to appearances,
which were attributed to a deposition of material, scrofulous or
tuberculous, from the blood or lymph. The idea was eventually
maintained that this material formed the basis of a growth or new
formation, and Virchow showed that the tubercle was composed of a
tissue, of cells and intercellular substance, growing within and from
pre-existing tissues. He classified the tubercles among the tumors as
circumscribed new formations whose structure resembled that of
granulation-tissue. The specific tubercle was, at the outset, minute,
smaller than a millet-seed, submiliary, although indefinite numbers of
these minute tubercles might be grouped together and form closely
massed aggregations. From this agglomeration of single tubercles, and
their frequent association with inflammatory products, both of which
were prone to early death and transformation into a cheese-like mass,
the extensive tubercular infiltrations of organs arose. The latter
were regarded as a frequent cause of the wasting disease phthisis,
which was either pulmonary, intestinal, or renal according as the
lungs, intestine and mesenteric glands, or kidneys were the
predominant seat of the tubercular growth.
The histological features of the tubercle were further investigated by
Wagner,[47] who described the resemblances and differences of the
structure of the tubercle and the lymphatic gland. Schüppel[48] soon
after published his monograph, essentially confirming the statements
of Wagner. According to these observers, the typical tubercle, as
found in lymphatic glands, presents essentially the same peculiarities
of structure when seen elsewhere in the body. This structure consists
of a non-vascularized network of fibres, in the meshes of which cells
are imbedded. The fibrous network resembles the reticulum of a
lymphatic gland, and nuclei are often found at those points where the
fibres are united. This appearance has suggested that the network is
formed of branching and anastomosing cells. Within the meshes are
three sorts of cells--viz. giant-cells, epithelioid (endothelioid)
cells, and small, round, indifferent cells. One or several
giant-cells, each with its abundant nuclei, lie near the centre of the
tubercle or are diffused throughout the same. These are usually
immediately surrounded by the large epithelioid cells, with one or
more nuclei, which are often so numerous as to compose the greater
part of the tubercle. The indifferent cells, resembling
lymph-corpuscles, occur singly or in groups, distributed throughout
the tubercle more abundantly at the periphery, between the cells
previously described, and with them completely fill the spaces of the
fibrous network.
[Footnote 47: "Das tuberkelähnliche Lymphadenom," _Archiv der
Heilkunde_, 1870, xi. 6; xii. 1.]
[Footnote 48: _Untersuchungen über Lymphdrüsen-Tuberkulose_, 1871.]
Although the typical tubercle is thus constituted, the structural
features depend somewhat upon its age. It is generally admitted that
the freshest tubercles, as found in the external coat of the smaller
arteries of the pia mater, are composed of little else than a
circumscribed accumulation of small, round cells, without a distinct
reticulum. The giant-cells, the epithelioid cells, and the
well-characterized reticulum appear as the tubercle increases in age.
It is thought probable that the giant-cells represent the
agglomeration of the small, round cells in pre-existing cavities,
lymphatics, blood-vessels, or secretory canals. The epithelioid cells
in like {96} manner are considered to result from the enlargement or
fusion of the smaller cells, while the reticulum represents either a
secretion from, or a transformation of, the cellular elements of which
the tubercle is composed.
The subsequent history of the tubercle is dependent upon its
metamorphoses. These are known as cheesy degeneration, calcification,
and fibrous transformation.
The absence of blood-vessels, already stated, and the abundantly
cellular nature of the growth, with the possible action of
micro-organisms, result in a tendency to the early death of the cells
and a necrosis of the tubercle. This is the cheesy degeneration, and
is regarded as a form of coagulative necrosis, which begins at the
centre, advances toward the periphery, and results in the
transformation of the gray into a yellow tubercle. This termination in
cheesy degeneration likewise affects inflammatory products surrounding
the tubercle, and even relatively normal tissues in which numerous
tubercles may lie. This cheesy material either softens or becomes
infiltrated with lime salts, calcified. The softening of the tubercle
results in the formation of a material capable of removal as a
discharge from the surfaces of the body or by absorption through the
lymphatics and blood-vessels. In the former event ulcers arise upon,
and cavities communicate with, the surfaces of the body opening
externally.
The cheesy material frequently becomes calcified, thus remaining as a
comparatively inert mass. The earthy salts may be diffused throughout
a uniformly cheesy basis, or they may be deposited in a partially
softened, cheesy menstruum, when a mortar-like material results.
The tubercle becomes fibrous with the diminution in the number of its
cells and the increase in the thickness of the reticulum, with the
transformation of the latter into a homogeneous hyaline substance. The
cornified, horn-like tubercle is one whose size is diminished from the
shrinkage of its cells into glistening flakes, without an evident
associated cheesy or fatty degeneration.
The intimate relation of scrofula to tuberculosis has been variously
expressed from time to time in accordance with the amount and accuracy
of the existing knowledge. At the outset the enlargement of the
lymphatic glands, especially of the neck, characterized the scrofulous
affection. As the enlargements of the glands were found to present
intrinsic differences connected with differing clinical histories,
only those glands were regarded as scrofulous which presented the
cheesy appearances. With the recognition of the cheesy condition of
tubercles the latter were identified with the scrofulous gland, from
the cheesy condition common to both.
This identification of scrofula and tubercle prevailed till Virchow
showed that cheesy material might have a different origin, and
maintained that there were cheesy lymphatic glands without tubercle,
as well as tuberculous lymphatic glands which might become cheesy. A
distinction was thus drawn between scrofula and tuberculosis. The
former term was applied to that condition of the individual which
favored the retention and cheesy degeneration of inflammatory
products, not only in the lymphatic glands, but elsewhere in the body.
Tuberculosis, on the contrary, was characterized by the production of
tubercles which were often accompanied by retained inflammatory
products, both of which were prone to undergo cheesy degeneration.
{97} The frequent association of well-defined tubercles with what were
regarded as antecedent scrofulous disturbances also suggested an
intimacy of relation between scrofula and tuberculosis. Virchow[49]
had always maintained the possibility of regarding tuberculosis as a
heteroplastic or metastatic scrofula. The occurrence of cases of
tuberculosis without evidence of an antecedent scrofula prevented him
from making a more absolute statement of the above relation.
[Footnote 49: _Die Krankhaften Geschwülste_, 1864-65, ii. 629.]
The views with regard to the connection between scrofula and
tuberculosis have become essentially modified of late years as a
result of the investigations concerning the etiology of tuberculosis.
In 1856, Buhl[50] first published his view, although he had for
several years been impressed with the idea, that miliary tuberculosis
was an infective disease resulting from the absorption of a specific
virus. He based his theory upon the almost constant coexistence of one
or several cheesy collections and miliary tubercles. The former were
recognized as the remains of previous inflammatory processes, and the
tubercles were looked upon as the immediate result of the absorption
of this cheesy material. The individual thus infected himself.
Buhl[51] claimed that the simultaneous occurrence of tubercles and
inflammatory products was the co-effect of the same cause, and that
the acute miliary tuberculosis, as a localized process, was merely an
inflammation with the development of tubercles. He restricted the term
tuberculous inflammation, however, to those forms which necessarily
and from the beginning, produced tubercles whose presence was limited
to the tissue inflamed. The tuberculous inflammation was regarded as a
primary condition, while the acute miliary tuberculosis was a
secondary process resulting from infection.
[Footnote 50: _Lungenentzündung, Tuberkulose und Schwindsucht_, 1872,
iii.]
[Footnote 51: _Op. cit._, 123.]
The tuberculous inflammation of this author was largely characterized
by those features which, with the exception of the constant presence
of tubercles, were recognized by others as attributes of a scrofulous
inflammation. At the same time, he objected to the latter term as a
substitute, since its use would imply that no other cheesy product
than that from a tuberculous inflammation would serve as the origin of
tubercles. Buhl strictly maintained that the absorption of any cheesy
material, whatsoever its source, might give rise to a general growth
of tubercle in the body.
The views of this author were popularized mainly through the teachings
of Niemeyer[52] concerning pulmonary consumption. The latter adhered
to Virchow's views relating to scrofulous inflammation, but maintained
that most consumptives were in imminent danger of becoming tuberculous
in accordance with the doctrines of Buhl.
[Footnote 52: _Klinische Vorträge über die Lungenschwindsucht_, 1867.]
The theory of an infectious origin of tuberculosis, advanced from time
to time by others, but most forcibly presented and maintained by Buhl,
was first demonstrated by Villemin[53] in 1865. This observer showed
that certain animals, especially rabbits and guinea-pigs, might be
successfully inoculated, beneath the skin, with fragments of gray
tubercle, cheesy products, sputum, and blood from cases of phthisis.
The development of tubercles took place within three weeks after the
{98} inoculation, and became general within four weeks. He also
demonstrated that rabbits became tuberculous when inoculated with bits
of the tumors occurring in the pearly distemper of cattle.
[Footnote 53: _Etudes sur la Tuberculose_, Paris, 1868, 528.]
Villemin's observations have been repeatedly confirmed and extended;
although subjected to the severest criticism and control, their
results are so constant that the law of the inoculability of tubercle
is almost universally regarded as fixed. Its value as a test is
evident from the statement of Cohnheim,[54] who regards as tuberculous
only that which produces tuberculosis when transferred to suitable
animals. The transfer may be made in various ways. Chauveau and others
were successful in producing an intestinal tuberculosis by the
introduction of tuberculous material into the intestinal canal of
animals, especially the Herbivora. Tappeiner[55] succeeded in
producing pulmonary tuberculosis, with or without general
tuberculosis, in dogs, by compelling them to breathe air in which were
contained minute particles of sputa from tuberculous pulmonary
cavities.
[Footnote 54: _Die Tuberkulose vom Standpunkte der Infections-Lehre_,
1880, 13.]
[Footnote 55: _Virchow's Archiv_, 1878, lxxiv. 393.]
The production of a tuberculosis of the iris, as well as of remote
organs, by the inoculation of tuberculous material into the anterior
chamber of the eye, was an ingenious method devised by Cohnheim and
Salomonsen.[56] It permitted the direct observation of the several
steps in the process of absorption of the inoculated material and
development of the tubercles.
[Footnote 56: Cohnheim's _Vorlesungen über Allgemeine Pathologie_, 2te
Auflage, 1882, i. 707.]
The objections to the various experiments above alluded to are based
upon the assumption that the results of the inoculation are not
tubercles, but inflammatory products resembling tubercles. It is
further advocated that the inoculation of indifferent material, as
bits of glass or hairs, as well as other foreign substances, will
produce the so-called artificial tuberculosis, especially in rabbits
and guinea-pigs. It is admitted that these animals readily become
tuberculous when exposed to simple inflammatory irritants, the local
action of which frequently results in the production of cheesy
material. This termination is now regarded as due to faults in the
method of experimentation, the animals not being thoroughly protected
from the influence of the virus of tuberculosis.
The objection on the ground of structure loses its force in connection
with the well known differences in the structure of miliary tubercles
in the human body, already mentioned. The tubercles resulting from
inoculation often resemble in structure the meningeal tubercles of the
brain rather than the type presented by tubercles in lymphatic glands.
The development of tubercles in the iris may take place without any
permanent inflammatory reaction. The association of evidences of
inflammation with the development of the tubercle is therefore
unnecessary.
The experiments of Villemin have not only demonstrated the infectious
nature of tuberculosis, but have also led to a more accurate knowledge
of the relation between tuberculosis and its allied affections,
scrofula and pearly distemper.
The anatomical characteristics of scrofula have obviously proved
insufficient in determining the relation presented by this affection
to tuberculosis. The tendency to cheesy degeneration of its
inflammatory {99} products was the feature of chief importance.
Villemin showed that portions of a scrofulous (cheesy) gland when
inoculated were followed by tuberculosis, and that the inoculation of
cheesy material from non-tuberculous or non-scrofulous sources was not
followed by this result. The assumption of Buhl, that the absorption
of cheesy material, as such, was the cause of tuberculosis, was thus
disproved. The frequency with which the inoculation of cheesy
material, from what were regarded as scrofulous sources, was followed
by tuberculosis, led to more exact studies concerning the anatomical
peculiarities of scrofulous inflammation. Köster[57] called attention
to the regularity of the occurrence of miliary tubercles in the
fungous granulations of the inflamed joints of scrofulous and
tuberculous individuals. Wagner[58] and Schüppel[59] discovered that
scrofulous glands, in most if not in all instances, were tuberculous
glands. The regularity of the presence of tubercles in scrofulous
abscesses and ulcers of the skin and in scrofulous caries was shown by
Friedländer.[60] This observer likewise called attention to the
presence of agglomerated tubercles as the chief constituent of the new
formation of lupus. These anatomical discoveries resulted in uniting
more closely the affections scrofula and tuberculosis from the
histological standpoint, and the union has become more firmly cemented
from the etiological investigations.
[Footnote 57: _Virchow's Archiv_, 1869, xlviii. 95.]
[Footnote 58: _Loc. cit._]
[Footnote 59: _Op. cit._]
[Footnote 60: _Volksmann's klinische Vorträge_, 1873, lxiv.]
Schüller[61] has shown that the introduction of finely divided
material from a scrofulous joint--that is, from one containing
tubercles--into the lungs of rabbits was followed by a tuberculosis of
the tracheal wound, the lungs, and liver. Similar experiments with
reference to the introduction of lupus-tissue produced results
suggestive of tubercle, if not actually tuberculous.
[Footnote 61: _Untersuchungen über die Enstehung und Ursachen der
Skrophulösen und Tuberkulösen Gelenkleiden_, 1880.]