T. Henry (Thomas Henry) Green.

An introduction to pathology and morbid anatomy online

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have already allowed for the tubercular. Moreover, there can be
little doubt that chronic bronchial catarrh facilitates tubercular
infection. This would be a case of grafting a tubercular affection
upon a simple chronic inflammation. To assume, however, that all
scrofulous glands, bones, and joints have begun as simple inflam-
mations, and that if they recover they have continued simple, but
have become tubercular if they take an opposite course, is a con-
clusion unsupported by evidence, and not in accordance with the
fact that the products of many long-quiescent scrofulous inflamma-
tions will excite general tuberculosis if inoculated upon animals.

LEPROSY.

This disease is endemic in many parts of the world, especially in
the East and West Indies, China, South America, and Equatorial
and Southern Africa. From the fourth to the fourteenth century
it was widely spread over Europe, reaching its highest point at the
time of the Crusades, when thousands in England, France, Ger-
many, and all round the Mediterranean suffered from the disease,
and numerous leper-asylums for the isolation of the afiiicted were
founded. It began to die away at the beginning of the fifteenth
century, and was relatively extinct by the end of that century,



444 THE INFECTIVE GRANULOMATA.

■when syphilis first become prominent. Leprosy still lingers in
many spots in Europe, particularly in Norway, Sweden, and Ice-
land.

VARIETIES. — There are two chief varieties of this disease —
tubercular and anaesthetic. In the former the lesions affect
chiefly the skin, in the latter chiefly the nerves.

In tubercular leprosy patches of hypersemia are followed by
thickening of the skin and the formation of nodules, which may
reach the size of walnuts. These changes are especially developed
on parts exposed to the air — face, hands, and feet — and appear
sometimes singly, sometimes in groups. They may begin as dis-
tinct eruptions, separated by long intervals of time. The affected
skin is first firm and red or brownish ; it then becomes soft and
pale ; unless injured, it does not, as a rule, ulcerate until long
afterward. When ulcers do form, they cause great destruction of
features and other parts {lepra mutilans). Healing may occur.
The nodules may affect other parts of the body, especially the
t'xtensor aspects of the limbs and the mucous membranes of the
eye, nose, mouth, and larynx.

In anaesthetic leprosy cylindrical or fusiform swellings occur
upon nerves, especially the ulnar and external popliteal. These
swellings surround long portions of the nerves, affecting primarily
the cutaneous and later the muscular branches. At first the skin
is often painful and hyperaesthetic ; later on it becomes anaesthetic,
pale, and, together with the paralyzed muscles, wastes. A bullous
eruption {pempMgiis leprosus) in the area of the affected nerve may
be the first sign of the disease : these bullae may either dry, leaving
pale insensitive patches, or they may be followed at once by ulcers.
Sooner or later ulcers form upon the anaesthetic parts, leading to
■extensive destruction, and even to dropping ofi", of fingers, toes, or
large portions of limbs (lepra mutilans).

The two forms may run their course separately, but often occur
together. The anaesthetic variety occurs chiefly in hot climates. In
each form the glands receiving lymph from the diseased pans
enlarge — first the superficial ones, then the deeper. Viscera —
especially the liver, spleen, and testes — may be also enlarged. In
the tubercular form death results from exhaustion or some intercur-
rent disease after a course of eight or ten years ; in the anaesthetic
form the duration is about twice as long.



LEPROSY. 445

HISTOLOG-Y. — To the naked eye the new tissue, wherever situ-
ate, has the grayish or yellowish, semi-transparent, uniform appear-



FiG. 150.



<\4^






AY




Tubercular leprosy— section through skin : a, showing infiltration with leprosy bacilli,
X 6; 6, showing bacilli in the cells, X 300 ; c, individual bacilli showing spores (?). x 800.
(Thin.)



ance common to so many structures. The loose areolar tissues are
chiefly affected, and, in a less degree, lymphoid tissue. Micro-
scopically, the nodules consist of four principal elements : (1) Large
numbers of small and often vacuolated epithelioid cells, generally
containing bacilli {vide infra), and frequently found in the lymph-
spaces, from the endothelial cells of which they are possibly
derived; (2) large masses, known as " lepra-cells," containing one
large vacuole and often a number of smaller ones, as well as bacilli,
granules, and occasionally many nuclei ; these lepra-cells may be
found inside lymphatics or encircling lymphatics or atrophied
sweat-glands : according to Metchnikoff, these are large mononu-
cleated leucocytes which have "engulfed" the bacilli; (3) clumps
of free bacilli in the lymphatics or elsewhere ; (4) an overgrowth
of fibrous tissue.

The new tissue in the skin ultimately undergoes degeneration,
and is absorbed or breaks down. The foci run together, and the
diseased part appears on section to be divided into nodular masses
by fibrous bands. Other tissues may, on account of the interference
with their nutrition, necrose or atrophy.

The lymphatic glands contain small fibrous patches. As Del^-
pine points out, the liver, spleen, and nerves all show signs of
chronic interstitial inflammation. The lungs are often said to be
tubercular. They certainly have the appearances of organs under-
going caseous broncho-pneumonia, but that this condition is really
due to a separate cause, such as tubercle, is doubtful.



446 THE INFECTIVE GBANULOMATA.

ETIOLOGY. — From time immemorial leprosy has been looked
upon as a contagious disease, and lepers have been rigorously
excluded from social communities. A very superficial examination
throws doubt upon this, for in many cases lepers have been known
to live in the closest association with healthy people without com-
municating the disease. Many observers have maintained that the
disease is communicable under certain conditions which are rarely
realized. It seems more difficult to prove the contagiousness of
leprosy than that of phthisis, and it certainly is not so great.

It may be noted that leprosy flourishes in all climates and upon
all soils ; that poor diet and salt fish do not appear to be special
factors in its etiology, as some have thought ; and that the disease
does not seem to be hereditary, although Hirsch held firmly to
the opposite conclusion. Children born of leprous parents in lep-
rous places may acquire the disease, but so may outsiders entering
such places. Possibly there may be some slight hereditary pre-
disposition analogous to that believed to exist in the case of
phthisis.

Observers are agreed that there is constantly present in all the
recent primary lesions of leprosy a bacillus very closely resembling
in its characters the tubercle bacillus (p. 415). So close is this
resemblance that the chief point of interest in the pathology of
this disease at the present moment is to determine whether the two
organisms are separate species or only modifications of a single
species.

The bacilli found in leprosy may vary in shape, size, and stain-
ing affinities. Del^pine showed that in a single patient the bacilli
free in the tissues were shorter and more readily stained than those
in the lepra-cells, while those in the skin and mucous membranes
were longer and more rapidly stained than those in the liver and
spleen. The bacilli are difficult to find, both in the neighborhood
of ulcerating surfaces and in the lungs. They are said to occur in
definite clumps (Hansen), and to be thus distinguishable from tuber-
cle bacilli.

Attempts to cultivate the organism have so generally failed that
the few recorded exceptions are of little value until more fully con-
firmed. Amid conditions under which the tubercle bacillus will
flourish the leprosy bacillus will not even grow at all.

Nor do inoculation-experiments give decisive results. In the case
■of a criminal the disease followed inoculation — offered as an alterna-



SYPHILIS. 447

■tive to execution — but the man had up to this point been in frequent
contact with lepers. Whether the infected tissues be introduced into
■oth6r parts of leprous patients or into animals, the results are uni-
formly unsuccessful, though the bacilli themselves are not destroyed,
for they can be found months afterward in the tissues.

The constancy of the association between (1) a certain set of
clinical manifestations, (2) a fairly definite series of pathological
changes, and (3) the invariable presence of a special bacillus con-
stitutes the greater part of the evidence in favor of the view that
this organism is a distinct species and the specific cause of the dis-
ease. It at present remains uncertain whether the organism is a
modified form of the tubercle bacillus or not. Delepine thus sums
Tip the evidence in favor of the view that it is such a modification :
" (1) The characters of the bacillus and its staining reactions ; (2)
the nature of some of the lesions ; (3) the frequency of phthisis and
scrofula in leprous patients (over twenty-five per cent.) or in their
antecedents ; (4) the difficulty of obtaining any result from inocu-
lation with the most typical and advanced leprotic lesions ; (5) the
success of inoculation with products obtained from organs less typi-
cally affected, such as the lungs ; (6) in case's of successful inocula-
tion the production of a disease which is generally tuberculous or
indistinguishable from tuberculosis."*

It seems strange, if this view be correct, that the reversion to the
original type does not take place more frequently, and that leprosy
as a clinical entity does not disappear.

SYPHILIS.

The lesions occurring in the course of constitutional syphilis also
belong to the class of Infective Granulomata. They are inflamma-
tory in their nature, but in their seats, distribution, sequence, and
histological characters present certain peculiarities which make
them characteristic of this disease. The primary syphilitic lesion
(usually the indurated chancre) occurring at the point of inocula-
tion is followed by enlargement of the neighboring lymphatic glands,
and later on, when the virus becomes generalized, by a series of
changes in the skin and mucous membranes. At a still later period
these may be succeeded by changes in the nervous system, bones,
and internal organs, most of them the results of inflammatory pro-

' The student is referred to a very able description of a case of this disease by
Delepine in Trans. Path. Soc. of London, vol. xlii. p. 386, 1891.



448 THE INFECTIVE GRANVLOMATA.

cesses induced by the syphilitic poison. Though not yet certainly
recognized, the nodular nature of the lesions demonstrates the
particulate nature of the cause, and the multiple foci of disease
prove its power of multiplication. Syphilis has now taken its place
in the classification of disease as a " chronic general infective
disease."

APPEARANCES. — I. Early Lesions. — Many of these are ana-
tomically indistinguishable from simple inflammations of the same
parts. The rashes, for example, are due to inflammatory hypersemia
with more or less infiltration of the superficial layer of the skin,
enlargement of the papillae, and often excessive epithelial multipli-
cation. As a rule, these inflammations end naturally in resolution,
but in tissues of feeble resisting power they may ulcerate. Early
syphilitic periostitis (nodes) is indistinguishable from traumatic
inflammation, and syphilitic iritis is diagnosed from rheumatic only
by concomitant circumstances.

II. Later Lesions. — The most frequent, but not the most cha-
racteristic, of these changes is fibroid induration. Anatomically,
this is ordinary productive inflammation, ending in scar-tissue (p.
294). When the fibrous tissue is gradually developed without evi-
dence of any change, except such degeneration and atrophy as may
depend on the subsequent contraction of this tissue, it is sometimes
spoken of as an overgrowth of connective tissue. Its appearance,
however, varies in different cases and in different parts of the same
organ. Sometimes the new tissue consists almost wholly of cells
with but little intercellular substance, sometimes of cells in a mark-
edly fibroid matrix, and at others of dense fibrous tissue only. The
infiltration may be general, but much more commonly the fibroid
areas are separated by comparatively healthy portions of the organ.
It is the irregular distribution of these lesions which makes them
so characteristic of syphilis.

The capsules of organs are irregularly thickened ; any peritoneal
coverings they may possess are sure to be involved ; and more or
less general adhesion to surrounding parts occurs. These changes
are seen in syphilitic hepatitis, splenitis, and orchitis. In orchitis
the coincidence of hydrocele proves during life the afi"ection of the
tunica vaginalis. The irregular thickening of the capsule is the
most marked feature.

As the fibrous tissue contracts the organ shrinks, and often



SYPHILIS. 449

becomes of stony hardness ; but the irregular distribution of the
exudation often causes unequal contraction and puckering of the
surface, amounting in some cases to the formation of deep fissures
which almost divide the organ into lobes. In these cases the diffuse
growth has probably been combined with the gummatous, and the
thickened capsule is connected with fibrous rays which extend
deeply into the surrounding tissue.

Naked-eye examination of a testis which has undergone these
changes shows adhesions between the layers of the tunica vaginalis,
with intervening spaces containing fluid, marked thickening of the
tunica albuginea, and, extending from it into the organ toward the
mediastinum, dense bands of fibrous tissue. The natural reddish-
brown color of the tubules is replaced by a much paler whitish-
yellow tint, in which islands of normal tissue may remain. The
consistence of the gland is greatly increased. One or two gum-
mata may also be present.

When occurring in bone, formations of this kind often ossify.
Under the periosteum they cause thickening of the bone. In the
Haversian canals and cancellous spaces they lead to increase in its
density.

These cell-formations do not always go on to fibroid induration ;
they may resolve, and under the influence of iodide of potassium
generally do so with marvellous rapidity, provided they are at all
recent. Probably the inflammatory products undergo fatty degen-
eration previous to absorption.

Gummata, Syphilitic Tumors, Syphilomata. — Anatomically,
these are the most characteristic lesions of syphilis ; they are fre-
quently associated with the fibroid induration just described. As
usually met with, they are moderately firm yellowish-white nodules,
having on section an appearance suggestive of the cut surface of a
horse-chestnut. They vary in size from a hempseed to a walnut,
and are surrounded by a zone of translucent fibrous-looking tissue,
which sometimes has the appearance of a capsule, and which is so
intimately associated with the surrounding structures that enuclea-
tion of the mass is impossible. The outline of the growth is gen-
erally irregular, owing to the number of fibrous processes which
radiate from it along the natural septa of the organ. In the earlier
stages of their development, when they less commonly come under
observation, gummata are much softer in consistence, more vascular,
and of a reddish-white color, whilst in their most advanced stages,

29



450



THE INFECTIVE OBANVLOMATA.



owing to extensive degenerative changes, they may be opaque, yel-
low, and fatty.

Examined microscopically, gummata are found to vary in their
minute structure according to their age. When recent they are
divisible into three zones. The central portions are composed of



Fig. 151.




Gummy growth from liver ; a,
central portions of growth, con-
sisting of granular d^hris ; 6,
peripheral granulation tissue ; r,
a blood-vessel. X 100. (Cornil
and Ranvier.)







The peripheral portion of a gummy
growth in the kidney, showing the
small-cell granulation-growth in the
intertubular tissue. X 200.



closely-packed sunken cells and nuclei, fat-granules, and cholesterin,
amongst which is generally a little fibrillated tissue (Fig. 151, a).
Surrounding this, and directly continuous with it, is the intermedi-
ate zone, consisting of epithelioid cells in a distinctly fibrillated
matrix. The peripheral portion of the growth (Fig. 151, h, and
Fig. 152), which is in direct histological continuity with the sur-
rounding structures, consists mainly of leucocytes, though epithe-
lioid and even giant-cells are also found. Giant-cells are much
rarer than in tubercle. The cells are separated by a scanty, homo-
geneous, intercellular material and numerous new blood-vessels.

In older gummata only two zones may be apparent — an inner or
caseous zone and an outer ox fibrous zone. The origin of the cells
in each case is most likely the same as in tubercle. It seems prob-
able, however, that the chemical effects of the syphilitic virus are
less deadly to the life of the new cells than are the corresponding
effects of the tubercular. The further development of the new tis-
sue therefore proceeds, and vessels are formed. The caseation
which next occurs is not so much due to the direct action of the
virus as to the subsequent shutting off of the blood-supply. By
means of changes presently to be described the walls of the blood-



SYPHILIS. 451

■vessels in the centre of a gumma become thickened, and in thicken-
ing encroach upon and nearly obliterate the lumen. Subsequent
thrombosis in the affected vessels completes the interference with
the blood-stream. To these changes must also be added the
strangulating effect on the blood-vessels produced by the contrac-
tion of the new fibrous tissue. The parts thus gradually deprived
of blood must degenerate, and this occurs at a comparatively early
stage, although not so early as in tubercle. When the gumma is
large, and particularly when the epithelioid cells are present in
large numbers, the mass may be seen to be made up of an agglom-
eration of smaller growths, each having the characteristic structure.
When the leucocytes especially predominate the foci run together
and their outlines are lost.

In early stages, before they have produced marked destruction
•of tissue, gummata may disappear. In later stages their central
fatty portions are frequently absorbed, leaving a radiating puckered
scar : calcification is rare. Not uncommonly, under conditions
which are not understood, gummata soften and excite suppuration
•around them ; the abscess bursts and a yellow slough is exposed.
This has a very characteristic appearance, like " wet wash-leather"
— tough and coherent, very unlike the dead tissue thrown out from
the caseous centre of a tubercular focus. It gradually becomes
•detached, leaving a larger or smaller cavity with soft ragged
margins. These changes can often be seen in the tongue. Gum-
mata of the sMn and mucous membranes are the most prone to take
"this course. These ulcerations must be distinguished from the
superficial ulcerations connected with the early rashes.

Gummata are met with in the skin and subcutaneous cellular
tissue ; in the submucous tissue, especially of the pharynx, soft
palate, tongue, and larynx ; in muscle, fasciae, and bone ; and in
the connective tissue of organs, especially of the liver, brain, tes-
ticle, and kidney. Gummata also occur, but much less frequently,
in the lungs, especially in congenital syphilis: simple localized
fibroid indurations are found under the same circumstances. They
generally form late, or "tertiary," manifestations, but they may
■occur at quite an early stage. No hard line can be drawn clinically
between the secondary and tertiary stages, and none can be drawn
pathologically between the products of these stages. Most are
inflammatory : of these some are circumscribed and some diffuse.
Hven the hard chancre has the same structure as the first stage of a



452 THE INFECTIVE GBANULOMATA.

gumma — leucocytes, epithelioid cells, and giant-cells in a fibrillar
matrix.

At various places attention has been drawn to resemblances and
distinctions between tubercular and syphilitic formations. The

Fig. 153.



i,




' ',//> 1 V« 's 1^






, >



Syphilitic disease of cerebral arteries: A, segment of middle cerebral artery, transverse
section ; i, thickened inner coat ; e, endothelium ; /, membrana fenestrata ; m, muscular coat ;
o, adventitia. X 200, reduced J. B, small artery of pia mater, transverse section, showing-
thickened inner coat, diminished lumen of vessel, and considerable infiltration of adven-
titia. The cavity of the vessel is occupied by a clot. X 100, reduced J. (Barlow.)

points of contrast may be thus summarized : In syphilis (1) the
contagion is more easily traceable ; (2) the foci are larger, and show
a greater tendency to organization, while endarteritis of their
vessels is invariable ; and (3) the lesions are always local and pig-
mentation is common.

Changes in Vessels. — Certain changes in the arteries, known as
endarteritis obliterans, occur in syphilis.

In the cerebral arteries the changes produce opacity and marked
thickening of the vessel, with considerable diminution in its calibre.
It is this diminution of the lumen of the vessel which is especially
characteristic. The smaller vessels, arteries and veins, are chiefly
affected, and their lumina may be quite obliterated.

When transverse sections of the vessels are examined microscopi-
cally the principal change is seen to be situated in the inner coat
(Fig. 153). This coat is considerably thickened by a cellular



SYPHTLTS. 453

growth. The growth, which is limited internally by the endothe-
lium of the vessel and externally by the membrana fenestrata, seems
to consist of "productive " inflammatory tissue (p. 294).

In addition to this change in the intima, the outer coat is abnor-
mally vascular and infiltrated with small cells (Fig. 153), and this
cellular infiltration usually invades the muscular layer as well. The
marked diminution of the lumen of the vessel, and the consequent
interference with the circulation, coupled with the changes in the
endothelium, frequently lead to coagulation of the blood (thrombosis)
and cerebral softening (pp. 76 and 267).

ETIOLOGY. — Strong as is the clinical evidence of the infective
nature of syphilis, nothing positive is known of its cause. The
general similarity between the lesions of syphilis and those of the
other infective granulomata lends weight to the supposition that the
virus is an organism which enters through a mucous membrane or
through an abraded surface of skin, and is carried into the blood
indirectly by the lymphatics, and directly by the blood itself; for
the early destruction of an infected surface fails to prevent the
general disease.

The poison exists in the primary sore, in mucous tubercles, and
all secondary sores, and in the blood during the eruptive period.
It is doubtful whether it is present in pure lymph, such as may be
obtained from a vaccine-vesicle. It is not present in normal secre-
tions, as saliva, mucus, semen. The discharge from tertiary or
gummatous ulcers is not infective.

Klebs inoculated apes with portions of syphilitic tissue, and pro-
duced a disease closely resembling syphilis.

During recent years many observers have described organisms
which they have found in syphilitic lesions. None of these results
have up to the present time been sufficiently confirmed. Lustgarten,
in particular, has described a bacillus very similar if not identical
with that usually present in the smegma preputii. But in this, as
in other cases, nothing certain is yet known.

Syphilitic Disease op the Liver.

The liver is one of the most frequent seats of syphilitic lesions.

The most common change is the development of fibroid and gummy

growths in the substa.nce of the organ. In the spreading stage the

margins of gummata are ill-defined round-cells infiltrating the sur-



454 THE INFECTIVE GBANVLOMATA.

rounding liver-tissue. The growths — which are usually connected
with fibroid thickenings of the capsule and adjacent peritoneum —
sometimes consist simply of a dense fibroid structure. More com-
monly, however, gummata are found imbedded in this fibroid growth.



Online LibraryT. Henry (Thomas Henry) GreenAn introduction to pathology and morbid anatomy → online text (page 41 of 57)