degeneration, its distribution in the various organs of the body is
fully ascertained, as well as certain of the conditions which are
likely to be followed by its presence. It is known to occur as a
localized process in cartilage, in the conjunctiva, in certain tumors,
cardiac thrombi, scars, retained inflammatory products, and renal
casts. The causes of this localized appearance are wholly obscure, and
little or no general inconvenience results. Its presence, however, on
a large scale and in various parts of {86} the body at the same time,
is met with under such circumstances as indicate a distinct
etiological relation. An appreciation of these circumstances is of
importance, since their existence demands an investigation as to the
probable presence of the degeneration. The organs thus affected are
the spleen, liver, kidneys, and intestine. It is to their disturbance
of function that the pathological importance of amyloid degeneration
is to be especially attributed.
Other organs which may sometimes be affected are the lymphatic glands,
pancreas, suprarenal capsules, omentum, uterus, bladder, prostate
gland, heart, and thyroid body. In the case of a general diffused
infiltration these organs are variously degenerated, now some, and
again others, showing a more extensive alteration, while few or many
may be simultaneously diseased. The longer the process has continued,
the greater the degree of the disturbance and the larger the number of
the organs infiltrated. Although, in general, a period of months and
years may be demanded for these extensive changes, very serious
disturbances may arise within a short time, and Cohnheim[37] records
several cases which suggest that widely diffused amyloid degeneration
may occur within a few months--in one instance in less than four
months.
[Footnote 37: _Virchow's Archiv_, 1872, liv. 271.]
All that is at present known with regard to the etiology of this
process applies to certain general diseases with which in the course
of time it is likely to be associated. These have one element in
common, that of chronicity, and are likewise the occasion of a
progressive wasting of the body. Of these affections, that which holds
the first place is chronic pulmonary consumption, especially that form
in which extensive destruction of the lungs and ulcers of the
intestine are present. Another disease whose effects are in like
manner to be regarded as general is syphilis, and in the later stages
of this disease amyloid degeneration is likely to occur, and often to
represent by its resulting disturbances the immediate cause of death.
Again, chronic suppurative processes, especially those due to disease
of the bones and joints, are a frequent antecedent of amyloid
degeneration. Finally, the process has been found in connection with
leucæmia, chronic intermittent fever, rickets, gout, and certain
malignant tumors. This last group, however, is one in whose sequence
the degeneration is to be regarded as exceptional.
The clinical importance of this process is due to the resulting
disturbances in the function of such important organs as the liver and
intestines, the spleen and lymphatic glands, and the kidneys. The
nature of these disturbances obviously demands detailed consideration
in connection with the description of the diseases of the respective
organs. It may be mentioned here that the infiltration of the walls
leads to a narrowing of the calibre of blood-vessels, and thus a
diminution in the supply of blood to the part or organ. The resulting
impairment of nutrition becomes enhanced from the condition of the
blood, which is impoverished from the simultaneous infiltration of the
blood-making organs. The nutrition of the individual thus suffers as
well as that of the immediately diseased organ. Fatty degeneration and
atrophy of the parenchymatous cells of organs like the liver and
kidneys is the constant result of long-continued and extensive
infiltration of these glands.
Mention is intentionally omitted of the so-called amyloid bodies, {87}
corpora amylacea, considered in connection with amyloid degeneration
in most text-books on pathology and pathological anatomy. They usually
present a different reaction with iodine, their origin has but little
in common, their distribution is for the most part unlike, and little
or no clinical importance is to be attached to their presence.
_Calcification, Ossification, Petrifaction._
When salts previously held in solution are precipitated under abnormal
circumstances in the tissues of the body, the part is said to be
calcified, ossified, or petrified. Although these terms are often used
as equivalent, the last is to be regarded as more general than its
predecessors, since it includes the deposition of other than the
calcareous salts.
In the pathological ossification, as well as its physiological
prototype, the carbonates and phosphates of calcium and magnesium are
present in a specially formed tissue of the nature of bone-cartilage,
whereas calcification occurs independently of such a new-formed
tissue. The deposition of the calcareous salts takes place either in
the cells or intercellular substance of living or dead tissues, when
the terms calcification or ossification are applied, or as
accumulations of various size in tissues or canals, which are known as
concretions and calculi.
The immediate causes of the physiological deposition in the formation
of bone are so obscure that only more or less probable explanatory
theories are advanced, to all of which obvious objections arise. The
causes of a pathological precipitation may be regarded as equally
hidden. It is apparent, however, that old age usually furnishes the
necessary factors. This in part may be due to the feeble nutrition
associated with impairment of function in advancing years. In part it
may be the result of the numerous opportunities offered in a long life
for the occurrence of inflammation, the products of which are
frequently infiltrated with calcareous salts. The latter are
apparently kept in solution by the action of living cells, for, though
presented to all in the fluids of the body, they are precipitated most
constantly in dead parts or in the vicinity of those cells whose
function is presumably lessened from disease or age. The solvent
action of living cells is further demonstrated by the effect of the
giant-cells in removing calcium salts from living or dead bone.
The causes of calcification are therefore to be regarded as local,
depending upon a destruction or weakening of the cells of a
part--conditions which are directly attributable to an interference
with nutrition. The deposition of calcium salts thus represents a
disorder of nutrition, and may be experimentally produced by agencies
which occasion a necrosis of tissues.
Although the immediate causes of the precipitation of the calcium
salts must be expressed somewhat vaguely, the places and effects of
their accumulation are sufficiently well known, as are the resulting
appearances. The presence of these salts in sufficient quantity
produces a homogeneous, granular, strongly refractive appearance of
the cell or intercellular substance, in addition to a greatly
increased resistance to pressure. When muriatic acid is added to the
affected part, the salts are dissolved, with the escape of abundant
bubbles of gas when a carbonate is present, and with a rapid fading of
the glistening appearance, without effervescence, {88} when the salt
is a phosphate. After the removal, the cell or intercellular substance
is readily recognized, with such modifications in its appearance as
may be due to the action of the strong acid. The parts in which this
deposition or infiltration has taken place are either relatively
normal in appearance or variously altered from disease, and the
calcium salts are to be regarded as absorbed from the constituents of
the food and deposited, or as taken up and transferred from the bones
of the body. That both sources are drawn upon is obvious from the
abnormal presence of calcareous material in the soft parts, in
connection with increased density of the bones, as well as with a
diminution in the density of the latter. The term calcification is
more correctly applied to the presence of the salts in normal tissues
other than bone, or in the products of disease not simulating
bone-cartilage in structure. A pathological ossification is to be
considered present when an actual new formation of bone has taken
place so limited and so situated as not to suggest a tumor of bone, or
when the calcium salts are deposited in a new-formed tissue whose
structure stimulates that of bone-cartilage.
Tissues which may become calcified are, in the first instance, the
connective tissues, and of these fibrous tissue and cartilage are
especially liable. Epithelial, muscle--in particular the unstriped
variety--and ganglion-cells may also become calcified. The frequency
with which blood-vessels, especially arteries, are affected is such
that it is regarded as almost normal in advancing years that
calcareous material should be deposited within the vascular walls. A
distinction is drawn between an ossification and a calcification of
the blood-vessels. The former term should be limited to the osteoid
plates so often found as circumscribed thickenings of the aortic
intima, and which are obviously new-formed patches of fibrous tissue
in which the calcium salts are accumulated. A calcified artery, on the
contrary, is one usually of a size varying between that of the common
iliac and the temporal arteries, whose wall has become rigid and
unyielding, suggestive of a pipe-stem, from the presence of calcareous
deposits in the muscular middle coat.
From the frequency with which the osseous plates of the aorta are
associated with the fatty and fibrous changes in chronic inflammation
of the intima, the so-called atheromatous degeneration of the same, it
is customary to speak of the calcified artery at the wrist or temple
as an atheromatous artery or as evincing an atheromatous degeneration.
The common feature in the aortic changes and in the calcified muscular
coat is the element of age. They are frequently, though not
necessarily, associated. The one is the result of an inflammatory
process productive of a new, fibrous, tissue in which the calcium
salts are infiltrated; while the other is due to a deposition of the
latter in the normal, pre-existing, muscular elements of the vessel.
Calcification and ossification of blood-vessels are frequent when the
latter become dilated, as in aneurisms, whether these occur as
circumscribed tumors or as a serpentine elongation and widening of the
affected vessel.
Cartilage is also a tissue which presents a double relation to
calcareous deposition. On the one hand, there may exist an
ossification resulting from the extension of a growth of bone from the
perichondrium into the cartilage. The structure of this bone presents
all the details found in {89} normal bone--lacunæ, lamellæ, and
marrow-spaces. On the other hand, a section of the cartilage,
especially the costal cartilages, may contain opaque, gray, or
grayish-yellow patches, grating under the knife, which are wholly due
to the presence of calcium salts in the hyaline intercellular
substance of the cartilage. This calcification of the cartilage, which
may also involve the capsules of the cells, is frequently associated
with an ossification, although this relation is in no way essential.
Calcification of the placenta, of the fibrous framework of the lungs,
of the mucous membrane of the stomach, or of the atrophied glomeruli
of the kidney, are well-recognized instances of the infiltration of
calcareous material in normal or atrophied tissues. On the contrary,
ossification of the fibrous inflammatory products of the pleura,
pericardium, and peritoneum are instances of a pathological
bone-formation, analogous in its nature to that met with in the intima
of the aorta. The fibrinous and fibrino-cellular products of the
inflammation of serous surfaces are favorable positions for the
deposition of calcium salts, as are thrombi arising from the walls of
blood-vessels. The latter are rather instances of the calcification of
dead parts, analogous to the members of the group which includes the
formation of calculi and concretions, the calcification of the dead
foetus in abdominal parturition, of cheesy lymphatic glands, and of
cheesy material in the lungs and elsewhere. Finally, there remains the
calcification of tumors of the most varied nature, the salts being
present either in living or dead parts of the tumor.
Instances of the deposition in the tissues of other than calcareous
salts are abundantly met with in gout. In this disease cartilage,
ligaments, and tendons, bone-marrow, muscle, the endocardium and
aorta, the membranes of the brain and spinal cord, the skin and
kidneys, may contain deposits of acicular crystals and amorphous
granules. Although these deposits are largely composed of sodium
urate, calcium urate may be present with other salts, as sodium
chloride and calcareous compounds. According to Ebstein,[38] the
earthy salts in gout are deposited in necrotic patches of previously
diseased tissue. The local conditions are therefore analogous to those
concerned in the formation of chalky concretions.
[Footnote 38: _Die Natur und Behandlung der Gicht_, Wiesbaden, 1882,
45.]
Concretions and calculi are collections of earthy salts, the former
lying within tissues, the latter being present in canals opening
externally. Both represent the results of a deposition in and upon
organic material, which is often an inflammatory product, at times
surrounding a foreign body acting as the exciting cause of the
inflammation.
The earthy matter of which the concretion is composed consists mainly
of carbonate and phosphate of calcium, while the chemical properties
of the calculi often vary in accordance with the nature of the
secretion which flows by them. The salivary, pancreatic, intestinal,
lachrymal, and prostatic calculi are chiefly formed of calcareous
salts. These salts also are an important, if not the chief,
constituent of biliary and urinary calculi. In the former pigment,
bile acids, and cholesterin may also be present. Urinary calculi are
of still more varied composition, containing not only the calcium
salts, as the oxalate, phosphate, and carbonate, but also uric acid
and the urates of sodium and ammonium, in addition to the
ammoniaco-magnesian phosphate.
The infiltration with calcium salts may prove beneficial as well as
{90} injurious--beneficial under those circumstances where further
changes might prove harmful, as in the softening of cheesy material or
the maceration of a dead foetus in the abdominal cavity. The
calcification of certain tumors, as the fibro-myoma of the uterus, is
equally sanatory, the further growth of the calcified parts being thus
checked. The calcification of an aneurismal sac may prove beneficial
in strengthening a weakened blood-vessel.
The injurious effects are seen more particularly in case of the
calcareous infiltration of the middle coat of arteries. Such vessels
become converted into rigid and unyielding tubes at various parts of
their course, and the nutrition of peripheral parts becomes
correspondingly lessened. Hence, in great measure, the liability of
old people to serious inflammatory processes from trivial irritation
of peripheral portions of the body, such inflammations often
terminating in gangrene.
The calcification and ossification of the cardiac valves and the
calcification of attached thrombi, furnish frequent and constant
occasion for disturbances in the functions of the heart, resulting in
dilatation and hypertrophy, with the sequence of symptoms of chronic
valvular endocarditis.
The great clinical importance of the presence of calcium salts in the
circulatory apparatus is such that further reference in this place to
its results is unnecessary, as its special relations are more
important than its general features.
Calculi act as local causes of inflammation, and their presence is
likely to be followed by ulceration, abscess, and stenosis, perhaps
obliteration, of the smaller canals in which they may lie.
_Pigmentation._
The pathological pigmentation of the body results, presumably, from
the metamorphosis of the coloring matter of the blood or from the
introduction from without of pigments insoluble in the fluids of the
body. The former of these methods has recently been studied by
Langhans[39] and Cordua,[40] and the present views of this subject are
chiefly due to their observations, as well as to the earlier
investigations of Virchow and others.
[Footnote 39: _Virchow's Archiv_, 1870, xlix. 66.]
[Footnote 40: _Ueber Resorptionsmechanismus von Blutergüssen_, Berlin,
1877.]
The hæmoglobin contained in red blood-corpuscles is considered to be
composed of a coloring matter, hæmatin, combined with an albuminate,
globulin. When blood is removed from the body the hæmoglobin is
readily separated from the corpuscles by various agents, and is then
dissolved in the plasma, which becomes lac-colored. This solubility of
the hæmoglobin is of importance in connection with the absorption of
extravasated blood. During the time necessary for this process to take
place, observable changes are apparent in the color of the affected
part when its seat is superficial, especially cutaneous. These changes
in color are largely dependent upon the modifications undergone by the
hæmoglobin.
It is well known that a yellowish discoloration of the general surface
frequently takes place when extensive internal hemorrhages have
occurred, constituting a form of jaundice (hæmatogenous) attributed to
the presence of the coloring matter of the blood. As yet there has
been no satisfactory chemical analysis of this diffused pigment, which
if not hæmatin must be regarded as its derivative, although a
coexistent increase of the urobilin in the urine has been observed.
The association of the stained skin and urine, {91} in the absence of
causes favoring an absorption of bile-pigment, leads to the inference
that the abnormal discoloration is due to the absorption into the
circulating fluids of the body of a pigment dissolved out of the
extravasated red blood-corpuscles. This view is confirmed by the
microscopic examination of the latter, which discloses the presence of
pale, shadowy, round outlines enclosing faintly granular material,
which are regarded as decolorized red corpuscles. In the course of a
few days glistening crystals and granules of a yellowish-red color
make their appearance in the midst of the unabsorbed blood. The
crystals are usually oblique rhombic prisms, varying in size from the
larger symmetrical shapes to the more minute, apparently granular,
forms. Acicular crystals are also to be met with, more yellow than red
in color, and are sometimes present in great abundance, although they
may be wholly absent. Virchow has applied the term hæmatoidin to these
crystals. Owing to the resemblance in the chemical reactions of
solutions of hæmatoidin and of the biliary coloring matter, bilirubin,
and to the similar crystalline forms of the latter, it has been
maintained that the two are identical. Late investigations indicate
that solutions of crystals with the appearances of hæmatoidin are not
invariably alike in their reaction. A solution of these in chloroform
may become decolorized when acted upon by a dilute alkali, or it may
not be thus altered. Bilirubin presents the former relation, while
chloroform solutions of the coloring matter of the yelk of egg and of
the corpus luteum, called lutein or hæmolutein, are not decolorized by
an alkali. Although the crystalline forms of hæmatoidin and bilirubin
are not to be distinguished, it is not to be conceded that the two
substances are identical. As Maly,[41] the latest writer on this
subject, states, the term hæmatoidin is merely indicative of a
microscopical picture. Although the identity of the coloring matter of
the blood and of the bile is not admitted, the intimate relation of
the two is not only suggested by the similarity of crystalline form,
but by the relation determined between urobilin, bilirubin, and
hæmoglobin. Urobilin is the coloring matter extracted from the urine
in fever by Jaffé, and it has since been obtained from bilirubin by
Maly,[42] who has given it the name of hydrobilirubin. This
hydrobilirubin has also been derived from hæmoglobin. According to
Maly, this genetic relation between the coloring matter of the blood
and bile, shown in the production of hydrobilirubin, is the only
chemical evidence of the connection of the two pigments.
[Footnote 41: _Hermann's Handbuch der Physiologie_, 1880, vii. 155.]
[Footnote 42: _Op. cit._, 161.]
Hæmatoidin is to be regarded not only as directly derived from
solutions of hæmoglobin, but as originating through the medium of
indifferent cells. Langhans claims that this pigment is formed within
movable cells which accumulate in great numbers in the vicinity of the
blood-clot, and, in virtue of their amoeboid properties, take into
themselves the extravasated corpuscles, entire or in fragments. The
indifferent cell may become enlarged into a giant-cell, and then
contain numbers of whole or disintegrated red corpuscles. In time
these colored corpuscles and fragments become smaller, more
glistening, and darker-colored, and eventually are transformed into
granular or crystalline hæmatoidin. These granules may be set free by
the fatty degeneration of the cell, or may be transferred within the
cell to distant parts.
{92} The diffusion and absorption of a solution of hæmoglobin, and the
formation of crystals of hæmatoidin from the same or through the
medium of cells, are supplemented by an apparent inspissation and
condensation of the hæmoglobin. The resulting dark-brown pigment may
remain at the seat of the hemorrhage indefinitely, and may be
accompanied with reddish-brown flakes, which, as shown by Kunkel,[43]
are composed of hydrated ferric oxide.
[Footnote 43: _Virchow's Archiv_, 1880, lxxxi. 381.]
Another feature in the absorption of extravasated blood is to be found
on examination of the nearest chain of lymphatic glands. These may be
seen swollen, of a dark-red color, and homogeneous surface. In density
and color, as well as shape, they suggest the small supplementary
spleens so frequently met with. These glands owe their change in
appearance to the presence of large numbers of unaltered red
blood-corpuscles which have entered the lymphatics traversing the
region of hemorrhage. Within the lymph-glands they undergo a
metamorphosis similar to that taking place at the part from which they
were transferred. In the course of weeks or months there remains in
the place of extravasation simply pigment, either as crystals or
granules. Such pigment may remain for years imbedded within the
tissues, or it may become absorbed, no trace of the original
disturbance remaining. Its removal may take place presumably through a
local solution of the pigment or the transfer of the granules or
crystals by means of wandering cells to the nearest lymphatic glands
or to the more remote parts of the body. An eventual elimination may
occur through the secretions, especially the urine or bile, or there
may result a deposition and permanent retention of the granules.
The investigations of Langhans are especially interesting, as
suggesting efficient means for the production of pigment by cells
whose function is intimately connected with pigmentation, as the cells
of the rete Malpighii, of the choroid, and of certain tumors. The
observations of Gussenbauer,[44] however, lead to the conclusion
earlier advanced by Virchow, that pigment may be produced by the
diffusion into cells, outside the vessels, of a solution of the
pigment of the blood in the plasma of the latter. A precipitation of
this dissolved pigment into granules is considered as eventually
taking place.
[Footnote 44: _Ibid._, 1875, lxiii. 322.]