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Pathogenesis
CHARLES
of
Tuberculosis
M.D.*
Introduction There ogenesis more cognize of opinion factors different quate are many unanswered of tuberculosis. However, complicated many in modifying conditions control events regard the and observations.
Some Basic Terms
the is
by
of may
difference fully
development
of
the
terms
to
be
employed
is
paramount
in
any
focus is the lesion produced with tubercie bacilli occurs. primary nodes. or focus and A progressive contiguous a period refers to dormant the
primary
involved of disease
lymphatic which
results
from
extension
a primary focus, tivity. Endogenous ease locus that time. Exogenous out which occurs infection. external culous lesions body, a caseous entirely tuberculoma center replaced source lesion. uniformly and implies is an
of comparative a reactivation for a variable infection a healed of infection an or size in This the in the
Miliary
of period
indicates individual
(if
from withtuberculous from tuberthe A contains may be or brain It may extension of progresa
endobron-
Superin/ection Miliary
It exists)
an
to numerous
millet-sized
dissemination variable
and by
metastases
secondary
Vol.
XVII
THE
PATHOGENESIS
OF
TUBERCULOSIS
sive used
disease, In
more
or less with
to an disease. of
organ
system,
connection
En try-3 of milk Is extensively pracwell over via the gastroof One a later entry Transportal portal
In
countries
pasteurization entry cases. skin and placenta the tissue tonsil, such Modes as of be is via the Occasionally focus has been at is rare, may the rarely in
ticed the portal 90 per cent of oral intestinal in of of ritual entry, entry mission cavity with tract.
respiratory there the other but not lung. tonsil mentioned sites is
a primary
preclude
may stream,
by
Basic The
Into the the lungs
individual
body may
unaware
time:
the lobe,
of
tubercle
of Infection
bacilli
in
some located
any to
usually
subpleurally.
After
an focus
weeks),
incubation the or
of
eight weeks (average can be elicited and or may not who be visible had children
primary by
lesions be
roentgenogram However, In
before cases
signs, when present, may be after infection occurs. Indeed, the only indication of infection, may malaise, be accompanied anorexia, by symptoms weight
demonstrated within the tuberculin reacor the period of and cough, signs. These wheezing,
loss,
increased erythrocyte sedimentation rate, neutrophilic leukocytosis followed by monocytosis or lymphocytosis, phlyctenular conj unctivitis and erythema nodosum. The last-mentioned is quite common in the Scandinavian countries, but is uncommon In the United by facfactors, In It the
Wall-
States. The subsequent course of events may be modified tors of indIvidual resistance, age, sex, race, soclo-economic
etc.2 ages
The
of
period
birth to
of
three
Initial
years
Invasion
and from
is second
especially
15 to 35
dangerous
years, which
gren
designates
as
the
first
and
danger
periods.1
Is like-
552 wise dangerous to be influenced in Minnesota During are the in than stage spread. disseminated the by in of
CHARLES
M.
NICE,
JR.
May,
1950
in some variations
social
Scandinavian Initial invasion this Is meant the reaction the Koch throughout
By
tubercle stream,
before6 the tuberculin tend to be localized by generalized result at at to to six a later months this
Subsequent when allergy tuberculosis tend to heal the completed may not initial the show hand,
develops. However, or meningitis may only After complex and/or triad evidence the primary period to phthlsis,9 tissue develop invasion tion of to reactivate four tends
stabilize,
roentgenogram.
other
lesion may proceed directly or a more advanced disease process,8 with extensive Involvement of the and and
after a variable latent or even to a wasting contiguous pulmonary pneumonia compression including These consist latter may or formaconto designate of caseous in a few nodule within only
(figure 2). Also, a non-caseating in the surrounding area, may cyst-like lead to blebs obstructive or bullae,
or serous bronchial
emphysema,#{176} atelectasis. as epituberculosis picture did not tissue, and could a small fibrous may result however, is usually
ditions were previously designated that the entire roentgenographic or tuberculous months, leaving as evidence In a high Since 9 to percentage the primary inflammatory at times This of cases, only
of disease.
atelectasis
in bronchiectasis
if it doesnt located
Involvement Focus
FIGURE 1: Basic
-+0
Pattern
Vol.
XVII
THE
PATHOGENESIS
OF
TUBERCULOSIS the result. controlled, may lead or multiple metastases. advanced this progression hematogenous other unhealed It may
the three
extension or primary or of
minimal
required effusion
to
reach may be
pleural
commonly
infiltrate,
tuberculomata Apico-caudad or even the organ far bacilli dismay lesions, is included result exacerbation,
plus the
foci) may
or
miliary endobronchial then produce moderately At blood any stream time during for
lesions. the
a secondary
or a small focus of disease in some progress and invade the blood stream. occurring but
or
in still
of
the awaits
the
presence definite
lung
of
this
wasting
proof. tissue
from
progression
of
reinfection,
the
primary
or from
lesion,
any one
endogenous
of
if disturbed.
other
the
than
and occur
disease
in to
any invade
organ the
a lesion blood
progress
to
produce
local
phthlsis
or
What We primary
Happens
Nodes?
(figure
3) of proceed the to
FIGURE
2: What
Happens
to the
Primary
Focus?
CHARLES
M. NICE,
JR.
May,
1950
The sputum,
caseous and
and larynx
node the
may bacilli
a bronchus,2 the
tract.
leading
com-
intracanalicular
Bronchial
gastro-intestinal
leads
to manifestations Discharge of a large blockage of the rima may perforate to the Rupture tuberculous and the subclavian of caseous pericarditis. leading atelectasis,
of obstructive emcaseous mass may glottis with sudden thoracic duct and initiate into difficulties may in turn the a the hilar vein to material Calcified to future which
node
may produce
bronchostenosis,3
to progressive
the
In
figure
shown. involve
Briefly, the
bronchial
Happens
to bacilluria
the
First may
Spread? demonstrable
(figure
5)
evidence
may occur in the absence some even believe that the or This is difficult meningitis may
tubercle to prove.
FIGURE
3: What
Happens
to Involved
Regional
Nodes?
Vol.
XVII
OF
TUBERCULOSIS
555 quiescent, years, but givIng hean while system less fre-
occur. may
or
disease and at times a chest roentgenogram healed lesion is starts lesion, present in the or in
tuberculous frequently
metaphysis,
FIGURE
4: Consequences
of First
Hematogenous
Dissemination.
Tuberculoma
of
brain
Paraverfebr& abscess
I
Tuberculous
I LffusIon
Pleural
meningihs
FIGURE
5:
What
Happens
to Progressive
Primary
Lesions?
CHARLES
M.
NICE,
JR.
May.
1950
The
may
penetrate in the
the
joints,
the cartilage.4 swelling which not and Indicate cyst-like the and the phalanges
is an allertwo to three bacilli diaphyses simulating of this thus form. the may be reLarge in the of
does bones in
Rarely, sarcold
lesions
for brain
meningitis tuberculomata
effusion.
or multiple
bacillary foci
pelvis
demonstrable
(without single
the
spleen or
from
either
thence may
lesions.
renal Tuberculous
Renal
tuberculosis5
intracanalicular
spread
to
Involve
ovaries
or
uterus.
Lesions
of
the
uveal
tract
pigmentation. Pat ho genesis of discussion occur in any by spreading must be kept focus that as Phthisiogenic and in In filtrates figure 6 it is seen that a
the
preceding
organ in which any tuberculous through the contiguous tissue. in mind from the time of the until the the therapy present, or primary death of the and other of the patient not form be of patient. should limited tuber-
process
designation
Secondary hematogenous
Spread is a term used in this that paper occurs who those lungs. postor
to indicate
hematogenous
of disease
the first hematogenous a progressive primary have lesions by one may the that in an first find a have area be Initiated
previously
established mortem
hematogenous
dissemination.
Vol.
xvii
THE
PATHOGENESIS
OF
TUBERCULOSIS
tuberculous
small caseous
meningitis
process
and
in in any
after
bone,
thorough
kidney, prostate,
produced
Any unhealed
the stream.
overwhelming
lesion
infection
organ
the
and
blood
Effect
In monia, children upper incidental respiratory
of
Non-Specific
disease infections, such
Diseases
as etc., non-tuberculous pneu-
may other
in
visible sputum or
of of
potent
disease. turn
In is less
activating
on but to
tuberculous
the occur.
temporarily disease
in of
positive,
demonstrable Necrotizing
lesions.6
progression pneumonia
Satisfactory
usually
presence
prevents
incidental
infections
may has
Loefflers
also of and
to
the
false
that chest
bacterial
tuberculous roentgenograms,
pneumonias,
progressed.
eosinophilic
in
possibility
reactions
in
bronchograms
lupus
effusions
be kept
such in
disseminated
erythematosis
must
Negative
Tuberculin may
infection
signify or of patients
that is in
sustained period.
A small
primary exacerreinfection
IInvolved
L Bronchial
regional
nodes
4
invasion
-i-Il
I1
Contiquous fhrough
Jr
spread +issue
Phthisis
CHARLES
M. NICE,
JR.
May,
1950
and
the
disappears. as a result
The of
tuberculin an incidental
test
become
tuberculosis
ing
of
in the late stages of generalized or after an overwhelming seedrupture of a subpleural focus. uncommon have without widely who factor. skin active for have Some allergy disease many controlled state to the years. a patients even protects This first in
Inadequate apparently the presence Whether the status infection, produce Individual may
Is not
an
sensitivity be attained
FIGURE
7:
Composite
Pattern
of Possibilities.
Vol.
XVII
THE
OF TUBERCULOSIS sensitivity appear some degree. that more problem In a the than
has
559 been reported.7 to separate facsay that this allergy immunity danger.
to
be
also due
Some
is dangerous, that co-exists Many studies controlled, but conclusions and proved discussion of
while with
protective offsets
discussing it is hoped
have been inadequately few years more scientific of the not be results, neglected. of this other paper. tried Further
problem
scope
The nosis
study alone
has
facets. Garland8
The
establish,
conditions that have caused alone. Beyond this each case agement, endless controversial seems logical recognition culous to aid lesions one in of and discussion. public Many opinions that the a unified as the depicted study
SUMMARY
physicians of
tuberthought
7 may
basic
pattern
of
tuberculous
theories of the mechanisms involved have been purposely in many instances, and indeed, many are unsolved. It is that further research and clinical observations will serve the evolution dogmatically or is the a in result of this disease. Although we may that a given lesion is a progressive of endogenous of the and exacerbation pathogenesis management or of of
to clarify further not be able to state primary exogenous tuberculosis each individual lesion
mecanismos
espera
y desde luego muchos que estudios ulteriores la evoluciOn para o es concepto de la asentar resultado patogenico
cllnica servir#{225}n para aclarar Aunque estamos incapacitados si una lesiOn exOgena, es una primaria unificaciOn clOn
progresiva del
560 culosis individual. The author wishes the National Jewish studying case material, Minnesota for helpful ayudara para
CHARLES
M.
NICE,
JR.
May,
1950
InterpretaciOn
y el tratamiento
de
cada
caso
to express gratitude to Dr. Allan Hurst and staff Hospital, Denver, Colorado, for the opportunity and to Dr. Jay Arthur Myers of the University guidance in the preparation of this paper. REFERENCES
of of of
J. A. and Waligren, A.: Pulmonary Tuberculosis in Adults and Children, Nelson Loose-Leaf Medicine, Thomas Nelson and Sons, New York. 2 Rich, A. R.: The Pathogenesis of Tuberculosis, Charles C. Thomas, Springfield, IllinoIs, 1944. 3 Caffey, J.: Pediatric X-ray Diagnosis, Year Book Publishers, 1945,
Chicago, Illinois.
1 Miller,
4 LevIne, M. I.: Sequence of Roentgen Evidence of Tuberculosis and Cutaneous Sensitivity to Tuberculin, Am. J. Dis. Child., 58:799, 1939. 5 Lincoln, D. M.: Hematogenous Tuberculosis in Children, Am. J. Dis. Child., 50:84, 1935. 6 Ornsteln, George G.: Hematogenous Dissemination of Tubercle Bacilli in Primary and Reinfection Forms of Tuberculosis, Sea View Hosp. Quart., 6:343, 1941. 7 Sweany, H. C.: Studies on the Nature of Primary Tuberculous Infection, Am. Rev. Tuberc., 27:559, 1933. 8 Auerbach, 0.: The Progressive Primary Complex, Am. Rev. Tuberc., 37:346, 1938. 9 Christlansen, N.: On the Different Forms of Phthisiogenous Infiltrates and the Development of Phthisis, Acta Rad., Vol. 30, Fasc. 1-2, 17-35, 1948. 10 Jullen-Marie, G. S. et Mathey, R.: LEmphyseme Bulleux Pseudocavitaire au cours de la Primo-Infection Tuberculeuse de LEnfant, Rev. de la Tub., Tome 12, No. 5-6, 331, 1948. 11 Jones, Edna M., Rafferty, T. N. and Willis, H. S.: Primary Tuberculosis, Complicated by Bronchial Tuberculosis with Atelectasis (Epituberculosis), Am. Rev. Tuberc., 46:392, 1942. 12 Gorgenyl-Gottche, 0. and Kasay, D.: Importance of Bronchial Rupture in Tuberculosis of Endothoracic Lymph Nodes, Am. J. Dis Child., 74:166, 1947. 13 Head, J. and Moen, C. W.: Late Non-Tuberculous Complications of Calcified Hilus Lymph Nodes, Am. Rev. Tuberc., 60:1, 1949. 14 Mann, K. J.: Lung Lesions in Skeletal Tuberculosis, Lancet, 2:744, 1946. 15 Ustvedt, H. J. and Wergeland, H.: Investigations on the Pathogenesis of Renal Tuberculosis, Acta Tbs., Vol. XXIII, Fasc. I, 36-62, 1949. 16 Baum, 0. S. and Baum, L. M.: The Effect of Non-Tuberculous Pulmonary Inflammation on Pulmonary Tuberculosis, Am. Rev. Tubere., 59:68, 1949. 17 Editorial: Cellular Transfer of Tuberculin Sensitivity, J.A.M.A., 141: 1301, 1949. 18 Garland, L. H.: Conditions to be Differentiated in the Roentgen Diagnosis of Pulmonary Tuberculosis, Ann. mt. Med., 29:878, 1948.