Запущенные формы туберкулеза легких.

Осложнения туберкулеза.
Chronic forms of TB.
5.1. Determination.
Chronic forms of TB is a fibro-cavernous and cirrhotic disease most commonly
localized in the pulmonary system as a result of gradual progression of TB. It is well
known as a chronic tuberculosis due to its generalization. Chronic tuberculosis is
defined by us when the disease is prolonged and involves several organs of the body.
Its typical characteristic is extension of focal, infiltrations and cavity changes amidst
more than 2 segments in one or two lungs and more pronounced clinical and
laboratory manifestations than in small forms. Besides it has sclerosis changes are
more or less expressed. It may arise in post primary TB infection.
5.2. Motivation. Knowing of this form is necessary to every doctor to timely detect
and prevent their progression and infection surrounding persons. To control
tuberculosis in the world today an additional approach would be most welcomed.
Preventing (or reducing) pulmonary cavity formation is one such approach that has
been almost completely neglected. Pulmonary cavity formation and the extracellular
growth of tubercle bacilli in cavities cause bronchial spread of the disease in adult
patients and spread of the bacillus to the environment where they infect other people.
Therefore, cavity formation perpetuates tuberculosis in mankind. If no cavities form,
the patient is much less infectious
5.3. Epidemiology. By defnition post primary TB infection means a new chronic
tuberculosis may be in adults from an inside source of infection. Thus plays a role
endogenous source. In its broader interpretation, chronic tuberculosis refers to a
pattern of disease that develops characteristically in adults who have usually had
evolution forms of TB previously. It implies a pattern of behavior of pulmonary
lesions often observed roentgenographically and characterized pathologically by
limitation to the lung; by progression with caseous sloughing, intrabronchial spread,
and cavity formation. All stages of progression may be seen together within the same
lung, and lymph node involvement is seldom extensive.
5.4. Pathogeny. A cavity has been defined in the radiology literature as
(pathologically) “a gas-filled space within a zone of pulmonary consolidation or
within a mass or nodule, produced by the expulsion of a necrotic part of the lesion via
the bronchial tree” and (radiographically) “a lucency within a zone of pulmonary
consolidation, a mass, or a nodule; hence, a lucent area within the lung that may or
may not contain a fluid level and that is surrounded by a wall, usually of varied
thickness”. In theory, one would like to distinguish a cavity from other air- or fluid-
filled lung structures with different pathophysiologies, but in practice, this is not
always possible. Mycobacterium tuberculosis generally has the highest prevalence of
cavities among persons with pulmonary disease of any infection, probably because
this pathogen causes extensive caseous necrosis. In the case of M. tuberculosis, the
tendency to form cavities is clearly advantageous to the propagation of the organism
because cavities contain large numbers of organisms, which can then be efficiently
aerosolized and transmitted to other susceptible hosts. Also, cavity formation often
allows the tubercle bacillus to multiply (extracellularly) to tremendous numbers.
Therefore, in humans almost all multidrug-resistant tubercle bacilli develop in
cavities. This communication reviews the literature on liquefaction and cavity
formation, and lists some of the responsible hydrolytic enzymes. It also describes a
simple method to identify inhibitory pharmaceuticals, i.e., to observe their effect on
the liquefaction and ulceration of skin lesions produced in rabbits by ascending
concentrations of live or dead tubercle bacilli
Cavities are influenced by antimicrobial therapy and usually respond in one of
several patterns.
1. In treatment failure, cavities remain open and bacilli are easily culturable from
the inner necrotic lining. There are degrees of treatment failure, however, and the
caseous lining is often limited or spotty and the capsule may be thin with few
tubercles and little granulation tissue.
2. The open-negative or cleansed cavity is frequently seen in connection with
chemotherapy. Its size may vary, and its lumen is grossly clean and devoid of caseous
material. Microscopically, however, the walls are lined with fibrous tissue that often
contains islands of caseation or granulation tissue. The draining bronchus is usually
open, and in larger cavities pulmonary vessels may traverse the spaces or lie in
trabeculae. With chemotherapy these vessels are not often aneurysmal and seldom
cause hemorrhage. Roentgenographically the wall is frequently thin, a characteristic
that gives it a cyst like appearance, but confusion with cysts is not often a pathologic
problem because of the presence of fibrosis in the wall and the occurrence of areas of
tuberculous granulation tissue. The thin roentgenographic appearance is due largely
to clearing of the inner caseous zone and conversion of the granulomatous capsule to
fibrous tissue. It is the extent of the fibrous transformation within the wall and the de-
gree of clearance of the bacillus-containing caseum that correlate with open
negativity. The likelihood of sterilization of this type of cavity has attractive
theoretical possibilities since antituberculous drugs act only on multiplying organisms
which frequent the inner zone of the cavity. The greatest failure of chemotherapy,
however, lies in the emergence of bacillary resistance, and it is in the walls of cavities
where this phenomenon, also engendered by bacillary multiplication, is most apt to
arise. Open cavities always carry this liability unless bacillary multiplication can be
stopped by effective initial chemotherapy.
3. Some cavities close and become filled with caseous material of variable
consistency. In a few such cavities the draining bronchus does not become completely
obliterated but remains patent, and epithelialization may occur at the bronchocavitary
junction, This epithelium, when present, usually grows inward from the bronchus and
may invade the cavity to a limited extent, but seldom completely epithelializes the
cavity. Its importance in contributing to bronchial patency and eventual drainage of
necrotic cavitary contents has been emphasized by Auerbach and Small In completely
blocked cavities the draining bronchus becomes obliterated by either organized
exudate or fibrosis, and healing follows a different pattern. When cavity closure and
healing have occurred, lung resection was seldom done, so pathologic observations
have been limited. The usual pathologic sequence of events in cavity closure is ab-
sorption of air, dehydration of remaining necrotic tissue with later calcium
deposition, and hyalinization of the fibrotic capsule. These changes occur more
rapidly after chemotherapy. Such lesions may appear roentgenographically as
calcified remnants or as stellate scars with radiating bands of fibrosis to the
surrounding lung. Complete fibrosis of cavitary remnants was described prior to
chemotherapy, so it is reasonable to assume its occurrence after chemotherapy. In
lesions in which die caseum is transformed into calcified, fibrous, or hyalinized
tissue, the eventual eradication of tubercle bacilli is likely.
5.5. Diagnosis of chronic pulmonary tuberculosis.
Clinical history
Pulmonary tuberculosis, sometimes even in an advanced stage, may occur in the
absence of recognized symptoms. After treatment has been started, however, the
patient often recognizes symptoms in retrospect.
Patterns of onset. It is very common for the onset to be insidious, with symptoms of
anorexia, fatigue, mild digestive disturbances, slow weight loss, and the lack of
stamina to complete a day's work. Considerable mental anxiety may at times
accompany these vague complaints. After several weeks or months, a low grade
elevation of temperature may appear, characteristically in the afternoon.
Another pattern of onset is often called catarrhal and is characterized principally by
productive cough, purulent sputum, and repeated occurrence of coryza like symptoms
with rhinorrhea, nasal congestion, and increased sputum.
Less frequently the pattern may be that of an acute febrile illness with the
rather abrupt onset of high fever, chills, rapid pulse, and weakness. Productive cough
usually follows with myalgia and sweating, often giving rise to an influenza like clin-
ical picture. These patients have frequently paid no attention to milder symptoms
which often have preceded such an episode, a situation not uncommon in the
uneducated, in alcoholics, or in persons who are debilitated with age or other disease.
An onset with blood in the sputum, even though small in amount, may startle the
patient into seeking medical attention.
Other less frequent modes of onset are with pleuritic pain, with hoarseness, or
with a painful perianal abscess.
Constitutional symptoms. Constitutional symptoms are of a more general nature and
consist of malaise, ease of fatigue with exertion, weakness, anorexia, weight loss,
fever, sweating which may be profuse and characteristically occurs at night, myalgia,
indigestion, and amenorrhea. Erythema nodosum which accompanies the primary
infection in younger age groups, an observation made less frequently to-day thanks to
BCG vaccination and short course of a not specific inflammatory process. Fever may
be high and somewhat septic type with a rapid pulse and suggestion of cardiac over
activity; the skin may be warm and moist, and such patients often appear
thyrotoxicosis. Anemia occasionally contributes to weakness or dizziness, and
various fluctuations in emotional state are common but as a rule not severe.
Thoracic symptoms. Cough is the most common symptom referable to the chest. It
is usually dry at first, but occasionally may be associated from the onset with
mucopurulent sputum or with blood. It is usually due to sloughing of small caseous
lesions with the presence of exudate in the bronchi, but other causes, which usually
occur later in the disease, are bronchial inflammation, tuberculous laryngitis, and in
the child die compression of bronchi by enlarged tracheobronchial lymph nodes. Ex-
pectoration of sputum usually appears gradually. The quantity and appearance of the
sputum may vary, but characteristically it is yellow, is neidier foul nor tenacious, and
does not tend to layer on standing.
Expectoration of blood is a common symptom in patients with advanced
tuberculosis. It is important for the physician to inquire carefully as to the source of
the blood, whether it appeared from the nose, the oral cavity, or die gums, or whether
its presence was associated with cough and expectoration. The blood more often
occurs in the form of small streaks in the sputum, but may appear suddenly in larger
quantities. The larger hemoptyses that occur during the course of progressive tuber-
culosis usually average about 1 or 2 ounces, but occasionally may be greater, and
streaking of darker blood may persist for 2 to 3 days. Much less frequently
pulmonary hemorrhage may amount to a loss of a pint or more with symptoms of
shock.
Chest pain is frequently caused by tuberculous pleurisy, which may be either an
early or a late complication of pulmonary tuberculosis. Characteristically, pleuritic
pain is sharp and accentuated by deep inspiration or cough. Such pain may emanate
from inflammation, on any pleural surface, and sites of anatomic origin such as the
diaphragmatic surface will influence the location. Spontaneous pneumothorax may
also complicate tuberculosis and usually produces sudden sharp pleuritic pain
accompanied by shortness of breath. Chronic or recurrent dull pain, aching, or
tightness in the chest is common as a sequel of pleural inflammation and may vary
with changes in barometric pressure, temperature, and amount of physical exertion.
Radicular or chest wall pain may be produced by tuberculous involvement of the
spine and the extension of a cold abscess along the intercostal fascial planes. Rarely
tuberculous pericarditis may give rise to pain in die precordial area.
Shortness of breath often occurs in association with pleuritic pain that limits the
depth of the patient's breathing. It may accompany a spontaneous pneumothorax or
large pleural effusion and may also indicate extensive tuberculous pulmonary in-
volvement. When associated with tuberculous pneumonia it is usually accompanied
by fever and chills, and when a result of more chronic pulmonary involvement it
characteristically follows exertion. Shortness of breath may also be associated with
wheezing and may result from obstruction of a major bronchus and pulmonary heart.
Wheezing is the usual complaint in patients with endobronchial tuberculosis.
Persistent unilateral wheezing is more indicative of localized endobronchitis, and
stridor may occur with ulceration and cicatrix of the trachea or larynx. Transient
wheezing from bronchial secretions usually clears with cough.
Hoarseness is usually present with tuberculous involvement of the larynx and is
often accompanied by severe pain.
History of exposure. When pulmonary tuberculosis is suspected, inquiry concerning
exposure of the patient to a person with an open case of pulmonary tuberculosis may
be helpful, especially if this contact has been a long and close one. The history of
exposure may be reinforced in the marital history, family history, or occupational
history.
Medical history. The physician must keep in mind the chronic nature of tuberculosis
and the fact that it may be very insidious in onset and may masquerade under a
variety of symptoms or recurrent respiratory illnesses. Of special importance is a
history of pleurisy with effusion from which the patient may have recovered after a
period of rest in bed. A past diagnosis of pneumonia, which has recurred from time to
time, should always arouse suspicion regarding tuberculosis. Obtaining all previous
chest roentgenograms for careful review is required procedure for an intelligent
appraisal of the presence of previous pneumonia. Other illnesses with which
tuberculosis is known to be associated should be kept in mind, such as uncontrolled
diabetes, alcoholism, undernutrition from a variety of causes, occupational exposure
to quartz dust or silica, or mental illness for which the patient has been hospitalized in
a mental institution. A history of tuberculosis from which the patient made a
"complete recovery" with no necessityfor further follow-up observation occasionally
reveals the diagnosis all too clearly. The long-term administration of corticosteroids
or corticotropin for arthritis, collagen disease, or other illnesses should always arouse
suspicion of tuberculosis. Occasionally previous scrofuloderma about the neck or a
history of a perianal fistula may be a clue.
Physical examination
An orderly routine in the completion of a thorough physical examination is to be
emphasized because complications of pulmonary tuberculosis may occur in many
other organ systems throughout the body. Other diseases may also coexist with
tuberculosis, and upon their recognition could depend the success or failure of
therapy. Although this discussion will be largely limited to examination of the chest, a
complete physical examination is imperative.
Examination of the chest. The chest examination should be carried out in a standard
manner by the use of inspection, palpation, percussion, and auscultation. Many
physical findings may have no roentgenographic counterparts; for example, the
alterations in breath sounds, rales, or rhonchi that indicate endobronchial involvement
are all quite evident on auscultation. Sometimes crepitant rales are present, and the
underlying parenchymal lesion or exudate cannot be seen on the x-ray film, while at
other times the lesion will be detected only on the roentgenogram. The presence and
distribution of physical signs will in general vary with the pattern and distribution of
lesions.
The cavity lesions may not be recognized by physical examination, or there may be
slight impairment of percussion note, broncho-vesicular breath sounds, and perhaps a
few crepitant rales, best heard following cough. The lobular and confluent pneumonic
lesions, depending on their extent, usually give rise to varying degrees of impaired
resonance to percussion, bronchovesicular to bronchial breath sounds, and rales of all
types, including both bubbling rhonchi and moist crepitant alveolar rales. In the
denser areas as seen on the roentgenogram, physical findings may differentiate
between collections of fluid and a consolidated tuberculous pneumonia.
Pulmonary disease which is extensive and of long standing may give rise to an
infinite variety of combinations of physical signs. Usually such lesions tend toward
fibrosis, and the resultant contracture leads to, asymmetry ill appearance and in
motion of the two sides of the chest, to displacement of the mediastinal structures and
trachea, to muscularatrophy, or to partial obstruction to venous return with dilatation
of superficial veins on the chest wall. Paralysis of nerves such as the sympathetics or
the phrenic nerve on one side or the other rarely occurs, but phrenic nerve paralysis
may ' cause a highly retracted and paralyzed diaphragm,. which can simulate physical
signs of fluid in the lower chest. Cavities that communicate with the bronchus and lie
peripherally may be associated with cavernous breathing and crepitant rales, while
cavities in the opposite lung with obstruction to their draining bronchi give no
diagnostic clues on physical examination.
Completion of the physical examination. The physician should remember the
importance of looking for evidence of present or past extrapulmonary tuberculosis in
such structures as the spine, lymph nodes, joints, and abdominal organs, including the
liver and spleen. Examination of the rectum may reveal a fistula in ano, and pelvic
examination may uncover genital tuberculosis in the female. The prostate or
epididymis is usually the involved genital structure in the male. Tuberculosis does not
commonly occur in the skin or the mucous membranes but should be kept in mind.
The eye may be the site of a phlyctenular conjunctivitis. A neurologic examination
often reveals mental aberrations, followed by nuchal rigidity, ocular palsies, or a
positive Kernig's sign in tuberculous meningitis. Changes in blood pressure or
pigmentation in the skin may give clues to adrenocortical insufficiency, occasionally
secondary to tuberculous involvement of the adrenals.
Roentgenographic examination. Despite the fact that roentgenographic examination
is in itself not diagnostic of pulmonary tuberculosis, it provides the physician with the
strongest of presumptive evidence and documents that evdence with reproducible
accuracy. A chest roentgenogram is required before the physician can exclude a
tuberculous lesion in the lung, so it is a necessary part of all diagnostic inquiries.
Confirmation by bacteriologic examination or by other procedures mentioned below
is required, however, to make a precise diagnosis.
Interpretation of the chest film. In chronic pulmonary tuberculosis the
interpretation of the chest roentgenogram assumes a very important role in detecting
the presence of disease and estimating its extent, location, probable nature, and
activity. In interpreting the presence of pulmonary tuberculosis, especially disease of
limited extent, it is important to keep in mind that approximately 25 percent of the
lung fields cannot be visualized on the conventional posteroanterior (PA) film. For
this reason a lateral chest film should be part of every regular roentgenographic
inquiry. The great superimposition of shadows on the lateral film often makes it
difficult to visualize smaller lesions (those less than 1 cm in size), particularly if their
density is not great; thus, other positional views are very helpful, especially if
confirmation is needed. Supplementary techniques, such as lordotic views and
laminagrams, may aid in the interpretation, especially when cavitation is suspected
from the standard films. It should be remembered that the histologic composition or
cause of a roentgenographic shadow cannot be determined from the film.
The localization of lesions is of considerable importance, and the tendency for
reinfection tuberculosis to occur in the upper and dorsal portions of the lungs has
been pointed out previously. Whenever possible the disease should be identified by
the lobe and bronchopulmonary segment in which it resides; this may be especially
difficult when fibrosis and contracture result in considerable distortion of normal
anatomic relationships. Stereoscopic views and various types of positioning may be
employed for more precise localization. Lesions which are apt to be difficult to
localize are those which project around the hilar regions of the PA films, since such
lesions may lie in any of the three lobes in the right lung or the two lobes in the left
lung. When lesions are close to the interlobar fissures, they may likewise be difficult
to localize unless the fissures are also visible. Positioning may bring out pleural
thickening or minimal interlobar effusions that are not visualized on standard films,
but may be readily seen by the foreshortening of lordotic exposures. Bronchography
and angiography help in localization by defining the general shape and contour of a
lobe or segment.
The concept of localization also involves consideration of the anatomic structures that
have been affected. Involvement of the lung, the pleura, or the lymph nodes is usually
fairly easy to define when the extent of involvement is great, but with limited disease
special techniques such as planigraphy are helpful. Obliteration of "the vascular
structures within the lung by pulmonary tuberculosisis commonplace, and its extent
and locality can be easily estimated with the pulmonary angiogram or the perfusion
scan. The pericardium, heart, great vessels, esophagus, thymus gland, and chest wall
are rarely involved, but these possible sites of involvement must be kept in mind in
roentgenographic interpretation; coordination with history and physical findings may
be of great help. Shadows in the costophrenic gutters may be confused with
subdiaphragmatic involvement, especially calcifying primary lesions, which may be
confused with splenic calcifications or calcium deposits in mesenteric lymph nodes.
The activity of a tuberculous lesion is evaluated by a combination of
roentgenographic observation and bacteriologic examination. Of paramount
importance from the radiologic standpoint is the availability of all previous chest
roentgenograms for comparison. Changes in the size and appearance of the lesions
within recent weeks or months usually indicate an activity that may not be apparent
on any single examination. The finding of tubercle bacilli in the sputum likewise
denotes the presence of clinical activity, but correlation with the roentgenograms is
often necessary to decide which lesions are active. Occasionally the source of
tubercle bacilli may not be apparent.
Correlation with other methods of examination. The importance of other forms of
examination has already been mentioned. Displaying the chest film while conducting
the physical examination adds greatly to the accuracy of each approach. If the
sequence of diagnostic events does not permit this, it will be to the physician's
advantage to reexamine the patient's chest when the x-ray film is available.
Since extensive tuberculosis may inflict serious functional damage upon the lung and
since healing processes almost always involve fibrosis, correlation of chest films with
the findings of pulmonary function examination are important, especially in planning
treatment. Although the chest roentgenogram may give valuable clues as to the
location and extent of the functional impairment, it must be recognized that these
estimates are not quantitatively accurate and should be confirmed by proper
physiologic measurements. Films taken in full inspiration and full expiration are
frequently helpful in noting the presence of pulmonary emphysema or the extent of
localized trapping of air. Careful fluoroscopy is preferable for evaluating the speed of
aeration of the lung fields; the relative mobility of the diaphragms and the chest wall;
the presence of abnormal motion, pulsation, or fixation of intrathoracic structures;
and the direction and timing of mediastinal shift.
In summary, estimations of the presence or absence of pulmonary disease, its
localization, character, and activity by roentgenographic examination may be more
accurately evaluated by correlation with physical examination and with laboratory
findings. The results of the tuberculin test, the finding of tubercle bacilli in the
sputum, and the presence or absence of symptoms are often crucial determinants in
chest film interpretation as well as in diagnosis.
Unnecessary radiation. A brief word should be mentioned concerning the problem
of unnecessary radiation. The medically justified usage of radiation techniques of one
type or another can scarcely be classified as unnecessary, but a great deal of attention
has been focused in recent years upon the gradually increasing opportunities for
cumulative radiation exposure to which the public is subject. The average well-
educated patient is aware of these so-called radiation hazards and often may question
the physician as to the necessity for roent-genographic examinations. Repeated
filming in tuberculosis is desirable, so radiologic exposure should be reduced as
much as is consistent with sound practice. In general, since fluoroscopy entails the
largest amount of exposure for both patient and physician, image intensification
should always be used with it. With proper techniques and the use of adequately
monitored x-ray equipment, the radiation exposure from conventional filming is
reduced to a low, harmless level.
When are pulmonary shadows interpreted as tuberculous? Although a final
diagnosis of pulmonary tuberculosis cannot be made by any method of
roentgenographic examination, an experienced radiologist or physician can usually
show, with great accuracy, very strong evidence for the diagnosis of tuberculosis.
Knowledge of the pathology of tuberculosis and an appreciation of the methods of
progression and of healing are essential to proper interpretation. The variations in a
roentgenographic picture are as infinite as the location, distribution, character, and
extent of the lesions themselves. The importance of serial x-ray films in evaluation of
the behavior of the lesions must again be stressed. For detailed descriptions of the
correlation between roentgenographic shadows and the various forms of pathologic
lesions in pulmonary tuberculosis.
If an interpretation of tuberculosis is made from a suspicious roentgenogram without
bacteriologic it’s not proof of the diagnosis, the requirement of a positive tuberculin
test should be met, and careful consideration of the differential diagnosis should not
reveal other likely diagnostic possibilities. Prolonged observation or therapeutic trial
may then lend further validity to such an interpretation, but errors by these ap-
proaches are to be expected. Most difficulties in the differential diagnosis arise in
situations in which tubercle bacilli are not demonstrable by smear or culture and in
circumstances in which other diseases such as carcinoma or pulmonary mycoses
coexist. In pulmonary lesions of limited extent, the more important differential
considerations are done of the solitary nodule or coin lesion and the limited
pneumonia of bacterial, mycoplasmal, viral, or fungal origin, in which the clearing or
resolution is delayed. Other confusing and commonly encountered lesions of limited
extent are localized pulmonary fibrosis, early carcinoma of the lung, and pulmonary
infarction. In the more extensive forms of tuberculosis, various types of pneumonia
ranging from bronchopneumonia to the dense confluent consolidation seen in lobar
pneumonia of pneumococcal origin must be considered. The acute cavitary forms of
tuberculosis need to be differentiated from lung abscess. Other chronic pulmonary
diseases which frequently are characterized by cavity formation are. the systemic
mycoses, notably coccidioidomycosis, histoplasmosis, and blastomycosis; broncho-
genic neoplasms with central necrosis and abscess formation; necrosis within
pulmonary infarcts; infection of acquired or congenital pulmonary cysts; cystic
bronchiectasis; and other necrotizing pneumonias such as that caused by Friedlander's
bacillus. Pulmonary tuberculosis of hematogenous or occasionally bronchogenous
origin has a rather diffuse finely reticulated appearance, and must be differentiated
from many other types of infection that behave in a similar manner: industrial
pneumoconioses such as silicosis, berylliosis, and asbestosis; metastatic neoplasms or
alveolar cell carcinoma; and many other generalized diseases such as sarcoidosis,
diffuse interstitial fibrosis, scleroderma (diffuse systemic sclerosis), or histiocytosis
X. Garland has listed the various conditions which must be considered in the
differential diagnosis of tuberculosis on the chest roentgenogram. From the
standpoint of symptoms and physical signs, the physician also has to consider other
conditions that may cause prolonged and obscure fevers, e.g., brucellosis, subphrenic
abscess, Hodgkin's disease involving the lung or mediastinal lymph nodes, and rarely
leukemia.
Burke and Wier have reviewed their experience with patients whose disease was
originally diagnosed in error as pulmonary tuberculosis. Of 3,422 hospital
admissions, some 608 patients (17.8%) were ultimately discharged with a diagnosis
of non-tuberculous pulmonary disease; the 10 leading nontuberculous conditions
encountered are shown below. From the experience of these authors it is also to be
noted that an appreciable number of patients were ultimately recognized as having no
pulmonary disease. A careful differential diagnostic study is often as important in
ruling out pulmonary disease as it is in identifying the presence of tuberculosis or any
of the above-mentioned conditions.
Tuberculin test. Koch recognized the biologic activity of the tubercle bacillus shortly
after he discovered the organism. He used the word tuberculin to designate the active
material in the liquid medium in which the organism had grown. Although Koch's
dream of using tuberculin as a therapeutic agent in tuberculosis was soon shattered,
the material has proved to be an invaluable aid in the diagnosis of the disease, in
defining the extent of the tuberculosis problem all over the world, and in under-
standing the immunology and pathogenesis of tuberculosis. In addition, modern
knowledge of the mechanisms of delayed hypersensitivity and cellular immunity is
based mainly on the study of tuberculosis including the reactions of the infected host
to products of the bacillus.
Koch produced his tuberculin by growing tubercle bacilli in glycerinated meat broth,
boiling to kill the organisms, evaporating the medium to one-tenth of the original
volume, and filtering to eliminate the bacilli. The finished product, which contained
about 40 percent glycerin, is now called Old Tuberculin (O.T.). The glycerinated meat
broth was later replaced by synthetic medium, and several other modifications of the
original protocol were incorporated in the manufacture of the O.T. preparations that
are now available. Seibert, in 1924, used the term purified protein derivative (PPD) to
describe the material she made from O.T. by precipitation with saturated ammonium
sulfate. She produced a large batch, designated PPD-S, in 1939 [161], which was
adopted by the World Health Organization in 1952 as the international standard
tuberculin. Five tuberculin units (TU) is defined as the activity contained in a
specified weight of Seibert's PPD-S in a specified phosphate buffer without
polysorbates (Tween). Unprotected tuberculin is inactivated rapidly by ultraviolet
light and by adsorption to glass and plastic. The addition of the wetting agent
polysorbate 80 (Tween 80) has allowed the production of tuberculin solutions with
much greater stability than was the case previously." ->
Many different mediods of applying tuberculin have been tried, but the Mantoux
technique of intradermal injection by needle and syringe is the most accurate and the
most widely used. There are also several multiple puncture devices by which
tuberculin may be driven into the skin by prongs either coated beforehand with the
material or activated by a spring or trigger mechanism to carry into the skin some
tuberculin previously spread on the skin surface. The multiple puncture tests are used
mainly as screening procedures with the understanding that all positive or doubtful
tests should be checked with the more' accurate Mantoux technique.
In the United States at present, all of the licensed preparations of PPD tuberculin
must be bioequivalent to 5-TU PPD-S, as demonstrated by comparative testing in
humans. In the routine test, 5 TU contained in 0.1 ml are injected into the skin by
needle and syringe; this corresponds to 0.1 *»g of the standard preparation and is
known as the intermediate-strength test. First-strength PPD corresponds to 1 TU and
is essentially a fivefold dilution of the former material. Second-strength PPD is a
calculated dilution based on the dosage determined to be 5 TU and is said to contain
from 100 to 250 TU. Protein antigens made from other species of mycobacteria
should not be called tuberculin, but rather kansasiin, aviin, or a similar term.
Tuberculin has three main uses: (1) as a public health measure to determine die extent
of tuberculous infection in a community or to pursue contact investigation, (2) for
surveillance or screening to determine if tuberculosis infection has occurred since the
last test (this may be useful in selected pediatric clinics and among high-risk groups
such as medical- and nursing personnel), and (3) as an aid in determining the cause of
illness of an individual patient.
For public health and surveillance, arbitrary definitions of a positive test have
evolved from large-scale observations in patients with proven tuberculosis and in
noninfected persons. Plotting the size of the reaction to 5 TU in patients with
tuberculosis yields a normal distribution curve with most readings falling between 10
and 25 mm and a mean of about 17 mm. Thus, the American Thoracic Society and
the Public Health Service-have chosen 10 mm or more of induration to a 5-TU test as
a definition of positive. Elsewhere in the world either 2 TU or 10 TU are used for die
routine test. It should be kept in mind that the reading of the test is a subjective
evaluation in which some variation must be expected [131]. Accuracy to less than 3
mm may be approached by averaging multiple readings made blindly by at least two
expert readers.
No arbitrary definition of a positive test should be attempted in the diagnostic
investigation of a sick patient. The intensity of the response may be diminished by
many factors which affect delayed hypersensitivity reactions in a nonspecific manner.
These factors or conditions include acute virus infections or vaccination with live
virus vaccines; immunosuppression by disease, drugs, or steroid hormones;
malnutrition, especially in children; the relative anergy associated with sarcoidosis
and malignancy, especially lymphomas; overwhelming infection of any kind; and the
waning of delayed hypersensitivity associated with advancing age. In addition, there
is a small proportion of individuals with active tuberculosis who have none of the
above conditions but who still do not react to ordinary doses of tuberculin when first
seen. Although recent publications have suggested that this proportion may be as high
as 20 to 25 percent, other observations have documented that it is usually no more
than 5 to 10 percent with the use of 5 TU, and 1 percent or less with second-strength
PPD. In a World Health Organization study of 3600 tuberculosis patients, published
in 1955, less than 2 percent had reactions smaller than 6 mm and less than 4 percent
had reactions smaller than 10 mm to 5 TU. In many cases of tuberculosis with an
initially negative skin test, the reaction changes to positive after a few weeks of
treatment when the patient is in better condition.
At the dosage recommended, tuberculin does not induce an immunologic response,
but there may be a "booster" effect in which a second application from 1 week to 12
months after an original negative test may then be positive as a result of a recall
phenomenon. This is usually seen in older people whose delayed hypersensitivity
reaction has waned over the years, but a similar phenomenon sometimes occurs in
children.
The tuberculin test with the materials available today is not highly specific because
M. tuberculosis shares many cell wall antigens with other mycobacteria and with
organisms of related genera, such as Nocardia and Corynebacterium. Tuberculin sen-
sitivity is a quantitative function and the application of higher concentrations will
increase the frequency and the size of these cross-reactions. Nevertheless, in the
diagnostic investigation of an individual patient, a negative second-strength test with
PPD is stronger evidence against the diagnosis of tuberculosis than is a negative
intermediate-strength test. Further discussion of tuberculin skin tests may be found in
two comprehensive reviews.
Bacteriologic examination. Procedures to be followed in obtaining suitable
specimens. However suggestive other methods might be, it is only by the
demonstration of the etiologic agent that a definitive diagnosis of tuberculosis can be
made. In pulmonary tuberculosis, examination of the sputum is convenient for this
demonstration. The specimen may be collected in a sterile, wide-mouthed bottle or
disposable cardboard cup. There are also disposable plastic sputum collection outfits
which consist of an inner centrifuge tube enclosed in an outer jar that are safer and
more convenient. The specimen can then be processed without transferring to another
container or centrifuge tube. The patient must be instructed not to deposit saliva or
postnasal drip into the container, but only the material that is brought up from the
chest by coughing or throat-clearing. The length of the collection period will depend
on the amount of sputum produced. Usually a 24-hour sample including two early
morning specimens is adequate. Examination of a single expectoration by smear may
be useful in establishing a diagnosis quickly.
When the patient cannot or will not produce an adequate specimen of sputum, it is
possible to obtain by gastric lavage the bronchopulmonary secretions that he has
unknowingly swallowed during the night. After the patient fasts for 9 hours, a sterile
rubber or plastic tube is passed into his stomach early in the morning before he arises.
The stomach contents are aspirated and collected in a! sterile container. If necessary, a
small amount of sterile water may be introduced to facilitate the washing. The
material must be processed without delay since the acidity and enzyme content of the
gastric juice are detrimental to the microorganism. Specimens of sputum induced by
the inhalation of heated aerosols of saline or water are as good as gastric lavage
specimens for the demonstration of acid-fast bacilli, and obtaining them is easier on
the patient and the physician.
Bronchial secretions may be obtained during bronchoscopy by simple suction, or by
the instillation of a small amount of sterile saline followed by aspiration. Sputum
produced after bronchoscopy may be most helpful.
Methods of demonstrating tubercle bacilli. Bacilli may be demonstrated by direct
microscopy, by culture, and by animal inoculation. Direct microscopy is important
because the results are available immediately, but the examination is not complete
unless cultures are made. From microscopic examination one can only note that acid-
fast bacilli are present or absent; a culture is necessary to determine the species of
Mycobacterium and, indeed, whether the organisms are mycobacteria or members of
another genus. Nocardia and diphtheroids may occur as acid-fast rods in the sputum.
For direct microscopy of sputum a purulent fleck is teased away from the main
specimen, placed on a glass slide, and crushed with a second slide, and a smear is
made by drawing the slides apart rapidly. The most widely used staining procedure is
the Ziehl-Neelsen method. The slide is flooded with carbolfuchsin and heated to
steaming for 3 minutes. It is then rinsed with water and decolorized with acid alcohol
until no more color appears in the washing. After it is again rinsed with water, it is
counterstained with methylene blue or brilliant green for 30 seconds. Finally die
slides are rinsed and dried. Modifications of the method include an overnight staining
procedure and a cold staining method in which penetration of the dye is achieved by
the addition of a detergent to the carbolfuchsin. Every slide should be examined for at
least 5 minutes, and preferably 10 to 15 minutes, before it is reported as negative.
When acid-fast bacilli are found, a rough estimate of their quantity should be
indicated by the use of the terms rare, few, or numerous. Many laboratories prefer to
use a fluorescent staining procedure which makes use of the fluorochrome dyes
auramine and rhodamine, or auramine alone [80].
Sputum and gastric contents are subjected to a concentration and decontamination
procedure before being planted on culture medium. The purposes are to liquefy and
homogenize the specimen, to eliminate other bacteria, and to reduce the material
containing the tubercle bacilli to a smaller volume. One popular method makes use of
sodium hydroxide. An equal amount of 4 percent aqueous sodium hydroxide is added
to the specimen, and the mixture is shaken vigorously for approximately 10 minutes.
It is then incubated at 37°C for a half hour or until'complete homogenization is
obtained, after which the specimen is centrifuged for 15 to 30 minutes. The
supernatant fluid is decanted, one drop of phenol-red indicator solution js added to
the sediment,-and enough normal hydrochloric acid is added to make the sediment
neutral. A recent modification of this procedure that has become popular makes use
of N-acetyl cysteine with sodium hydroxide for more rapid sputum digestion [90]. A
loop of the sediment may be smeared on a slide for staining and microscopy and the
remainder used for cultural procedures. The sediment is spread evenly over the
surfaces of at least two slants or plates of culture medium with a sterile capillary
pipette or swab. There are many culture media available. As some strains will grow
better on one type of medium than on another, it is best to use two different media for
each specimen. Currently, the most popular medium makes use of the buffered egg-
potato formula of Lowen-stein-Jensen. Middlebrook's oleic acid-agar medium is also
widely used. It is recommended that cultures be made routinely on plates of the
Middle-brook medium, commonly known as 7H-10 agar, and slants of Lowenstein-
Jensen medium. Body fluids and homogenized sterile tissues should also be cultured
in liquid Tween-albumin medium (7H-9 broth).
The cultures should be incubated at 37 °C, preferably in an atmosphere of 5 to 10
percent carbon dioxide, and examined at weekly intervals. Slants should not be
discarded for at least 8 weeks, and they may be kept longer if facilities permit since
an occasional culture becomes positive only after 8 weeks. Plates of 7H-10 agar may
be discarded after 4 weeks. It is recommended that after each examination all cultures
with visible growth be exposed to light for approximately I hour to allow any
photochromogenic strains to develop their pigmentation. An experienced technician
can recognize a colony of Af. tuberculosis by its appearance on the culture medium.
Other mycobacteria can usually be distinguished by differences in growth rate,
pigmentation, and colony morphology. The reader is referred to the Center for
Disease Control (CDC) laboratory manual for further details on mycobacteriologic
methods.
Guinea pig inoculation and good cultural technique are about equal in detecting
tubercle bacilli. For animal inoculation, specimens need not be decontaminated and
therefore the suppressive effect of the digestion process may be avoided. In addition,
larger amounts of material can be injected into 2 guinea pigs than can be deposited on
several culture slants. Guinea pigs are especially useful for sputum or urine
specimens repeatedly contaminated on culture, forspecimens consistently positive on
microscopy but which yield negative cultures, for resected lung: lesions, and for
pleural and spinal fluids. Cultures must be done simultaneously since isoniazid-
resistant tubercle bacilli and other species of mycobacteria may not produce progres-
sive disease in guinea pigs but usually will yield a positive culture. The expense of
purchase and maintenance of laboratory animals has all but eliminated the use of
guinea pigs for the diagnosis of tuberculosis.
Resected lung lesions and biopsy specimens should be examined
bacteriologically as well as histologically. Separate sterile instruments should be used
on different lesions and aseptic conditions should be maintained throughout the
procedure. If the contents of a lesion are sufficiently fluid, they can be removed with
a sterile swab or pipette. The overlying tissue should be seared before incising the
lesion with a sterile knife. Direct smears should be made from fluid and necrotic
material. Fluid material may be prepared for culture by suspending it in sterile saline.
Tissue is homogenized in sterile mortars or tissue grinders. These specimens should
not be digested but should be cultured directly.
Significance of positive and negative bacteria-logic findings. The isolation of even
one colony of M. tuberculosis provides evidence of tuberculous disease. Very rare
exceptions to this rule will be afforded by errors in labeling specimens or tubes and
by accidental contamination. It is, of course, necessary for laboratory personnel to be
able to distinguish other mycobacteria from M. tuberculosis, since the former may be
found in small numbers in the sputum and gastric contents of healthy persons. The
finding of at least several acid-fast bacilli in the sputum or gastric contents by smear
is not adequate proof of the diagnosis but is strong evidence in favor of tuberculous
disease when the clinical picture and roentgenographic findings are compatible.
Negative findings cannot be relied upon to rule out the diagnosis of tuberculosis.
Providing the techniques are adequate, however, the repetition of negative results
makes the diagnosis more and more unlikely as the number of examinations in-
creases. For example, if the presence of a cavitary lesion and copious amounts of
purulent sputum is caused by tuberculosis, acid-fast bacilli should be found in the
direct smear of the first or second sputum specimen. When the number of organisms
is too small to be recognized by microscopy, culture of three consecutive specimens
should provide a positive result in 3 to 6 weeks. Completely negative results suggest
that one is dealing with another disease. On the other hand, with a minimal pul-
monary lesion without evidence of cavity one cannot exclude the diagnosis of
tuberculosis no matter how many negative results are returned. Even with minimal
disease, however, the majority of patients will produce a positive culture if enough
specimens are examined in an adequate manner.
Drug susceptibility tests. Determination of the susceptibility of a patient's tubercle
bacilli to antituberculosis drugs is desirable for the intelligent use of chemotherapy.
There are two situations in which susceptibility studies are especially important: to
detect primary drug resistance in new cases and to help in the choice of drugs for
patients requiring retreatment. Tests are performed by comparing the amount of
growth in a medium containing various concentrations of the, drugs with that in a
control medium without drugs. When abundant growth is expected because of the
finding of many organisms in the direct microscopy, a direct test may be used in
which the diagnostic specimen, after suitable preparation, is planted directly on a
series of slants or plates including both drug-containing and control media. Indirect
tests may be done by planting either from a liquid medium subculture onto a similar
series of slants or plates or from a suspension of bacilli prepared from a primary
isolation culture. The direct test has the obvious advantage of rapidity, but results are
not valid when growth on the control medium is scanty.
One notes the degree of resistance to each concentration of the drug, as evidenced by
comparison of growth in the drug-containing tube with that in the control tube.
Resistance to each drug may also be expressed as a resistance ratio in terms of a
comparison of the patient's organisms with the resistance pattern of a standard strain,
such as H37Rv, a subculture of which is included in each series of tests. The in vitro
drug susceptibility tests indicate die ability of a substantial proportion of the
population of bacilli tested to grow in certain concentrations of the drug, but they do
not always reflect the possible beneficial effects that can be obtained by the
administration of the drug to a patient. Experience has shown, however, that die
chances of successful treatment with a drug are poor when diere is even a low degree
of in vitro bacillary resistance to that drug (see Drug Resistance, below, for further
discussion).
Other laboratory tests. A number of blood tests have been used to gain information
about the activity and progress of tuberculosis, but most of them have little specific
value in diagnosis or prognosis. Many varieties of antibody tests have been proposed
for the detection of active tuberculosis; none has proved to be useful clinically so far.
Both the sedimentation rate and C-reactive protein have been used as an index of the
activity of the tuberculosis and as a guide to its quiescence. Neither test is specific for
tuberculosis. The leukocyte count is sometimes elevated in acute pulmonary
tuberculosis to as high as 12,000 to 15,000 cells per cubic millimeter. Usually
the...percentage of polymorphonuclear leukocytes is increased with a rise in young
forms; the monocytes are elevated slightly and the lymphocytes decreased. Character-
istically, as activity of the disease subsides the lymphocytes and monocytes return to
normal, and if elevated the neutrophils diminish proportionately. These changes are
not specific.
Tuberculous bacteremia is rarely detected but may be present during acute
hematogenous dissemination. It should be sought by inoculating blood into a liquid
medium such as 7H-9 broth. Tubercle bacilli may also be demonstrated by culture of
bone marrow.
Bronchoscopy. Indications. Bronchoscopy is occasionally a very useful procedure in
tuberculosis both from a diagnostic standpoint and by virtue of its value in the
management of the disease. It is preferable to gastric aspiration when the differential
diagnosis of carcinoma must be considered, since bronchial secretions are readily
available for cytologic study as well as for acid-fast smear and culture, while at the
same time careful evaluation of the tracheobronchial tree can be carried out for the
suspected neoplasm.
The suspicion of tracheobronchial tuberculosis provides an important indication for
bronchoscopy. The presence of a wheeze, of persistent and uncontrollable cough, or
of tubercle bacilli in the sputum without an obvious source in the lung parenchyma
offers sufficient reason for the procedure. Roentgenographic findings of atelectasis or
selective segmental or lobar collapse, unexplained shadows near the hilum, the
sudden or gradual appearance of localized obstructive overdistention, or ballooning
cavities should also be investigated by bronchoscopy. Identification of the source of
pulmonary bleeding may provide valuable information, especially if surgery is
contemplated. It is frequently possible to identify die lobe and segmental orifice from
which the bleeding originates. Finally, the diagnostic use of bronchoscopy to obtain a
biopsy from an area of bronchial ulceration or obstruction may clinch the diagnosis of
tuberculosis. Biopsy procedures are frequently helpful when tubercle bacilli cannot
be recovered or appropriate secretions are not available. Needle techniques are
occasionally used but surgical excision of involved tissue is more generally
performed. Staining and subsequent identification of acid-fast organisms in tissue
which histologically resembles tuberculosis is usually interpreted as adequate proof
of diagnosis. The presence of caseating tubercles provides strong evidence but is not
diagnostic. Appropriate maceration and culturing of a portion of the tissue is highly
desirable, however, and should be done with every biopsy to facilitate identification
of the organism present in the lesion. Granulomas with or without caseation may
occur in many other diseases such as sarcoidosis, histoplasmosis, brucellosis,
berylliosis, occasionally syphilis, and in other fungus infections, so staining or
culturing of the organism is important.
Lymph node biopsy. When the diagnosis of tuberculosis has been difficult, an
accessible lymph node in the neck or axilla may give valuable information.
Mediastinoscopy may provide access for biopsy of mediastinal lymph nodes, and
occasionally scalene node biopsy is helpful in disseminated pulmonary disease. Care
should be taken to request that a sizable portion of the specimen be sent to the
bacteriologist for examination.
Pleural biopsy. When a pleural effusion is present, the parietal pleura may easily be
biopsied with an appropriate needle, such as the Franklin modification of the Vim-
Silverman needle or the Cope needle. Care should be taken not to traumatize the lung
unnecessarily. Usually two or three pieces of parietal pleura may be obtained from
one puncture site by directing the needle to different areas of the parietal pleura.
Another approach is that of a limited thoracotomy incision, which requires the
services of a surgeon, but it has the advantage of accessibility to larger pieces of
tissue, which can often be palpated and evaluated as to their disease-containing
possibilities before they are removed. Pleural tissue also may be obtained under direct
vision by thoracoscopy. Culture of the homogenized tissue is more sensitive than
culture of the pleural fluid for the diagnosis of tuberculosis.
Bone marrow biopsy. Aspiration of bone marrow or biopsy of the bone and marrow
by a trephining technique is often helpful in establishing a diagnosis of miliary
tuberculosis. Tubercles or stained acid-fast organisms or bodi may be demonstrated,
and tubercle bacilli may occasionally be cultured from the specimens.
Lung biopsy. When other methods have (ailed to enable the physician to arrive at a
definite diagnosis, biopsy of a diseased area of lung under the direct vision and
control of the surgeon may be advisable. This is more often employed when the
differential diagnosis between tuberculosis and carcinoma is difficult, or when a
disseminated lesion remains undiagnosed and the possibility of miliary tuberculosis is
great. Once again, bacteriologic study of a portion of the tissue is helpful.
Evaluation of pulmonary function in tuberculosis
Evaluation of the extent and character of altered cardiopulmonary physiology in
tuberculosis may be of little help or consequence in the limited forms of pulmonary
tuberculosis, but detailed knowledge of the pattern of physiologic impairment may be
of paramount importance in extensive tuberculosis or in connection with pulmonary
surgery. With the great variation of pulmonary and thoracic abnormalities that may
occur in tuberculosis, and with the tendency for destruction and repair either to occur
sequentially or to coexist, a thorough evaluation of all the functional derangements
requires a well-equipped laboratory and trained personnel. Associated and complicat-
ing conditions such as emphysema, pulmonary or pleural fibrosis, and pulmonary
hypertension with cor .pulmonale, some of which are already present in many
patients, may be aggravated by tuberculosis to an extent that makes functional
evaluation necessary in planning therapy, in recommending rehabilitation, and in
conducting an intelligent follow-up program.
Diagnostic uses. There is no characteristic or pathognomonic pattern of physiologic
disturbance in pulmonary tuberculosis. From a strictly diagnostic standpoint, the
value of functional measurement lies chiefly in determining the extent and location of
damage caused by the tuberculosis, the presence and extent of coexisting diseases or
sequelae that may affect the function of die lungs, and the identification of the
existing type of physiologic abnormality so that proper therapeutic measures may be
carried out with a minimum of risk for the patient. In minimal and to a lesser extent
in moderately advanced pulmonary tuberculosis, there is seldom any significant
alteration of function tests. Exudative lesions, even though extensive, may resolve if
treated sufficiently early and may leave little functional impairment. The more severe
physiologic abnormalities that occur in limited tuberculosis are related to
complications such as pleural effusion, atelectasis, or fibrosis rather than to the
limited damage caused by the parenchymal tuberculosis.
In uncomplicated, far-advanced, destructive pulmonary tuberculosis there may be an
alteration of some degree in every measurable component of function, but the usual
pattern is that of a predominantly restrictive ventilatory defect with little or no arterial
hypoxemia at rest and seldom any further oxygen undersaturation with moderate ex-
ercise. Pulmonary artery hypertension may be seen after exercise in patients with
extensive tuberculosis and is thought to be related more to the destruction of the
vascular bed than to hypoxia or to transient hemodynamic phenomena, and for
similar reasons right ventricular work is seldom increased at rest. Cardiac output is
usually within normal range. Intrapulmonary gas distribution is often unequal,
depending on the type and location of the lesions, and in advanced destructive disease
there is usually much variability because of the size and alveolar ventilation rate of
the slow spaces. The residual volume usually remains normal or reduced but the
residual volume/total lung capacity (RV/ TLC) ratio may be increased, mostly
because of relative reduction of the total lung capacity.
Extensive, predominantly pneumonic tuberculous lesions may produce functional
abnormalities similar to other pneumonias. An increase in venous admixture may
occur early in the course of pneumonia, but caseation usually eliminates the involved
vascular bed as well as the ventilating alveoli; eventually a degree of balance is
achieved so that cyanosis or arterial hypoxia may not be conspicuous unless the
diffusional surface is greatly decreased. Other components of function such as the
gross ventilatory measurements are reduced in a restrictive type of pattern.
Hypercapnia is not seen unless associated emphysema or bronchitis is present.
In tuberculosis that has been extensive and in which fibrosis has occurred, the pattern
is more apt to be mixed. More of an obstructive element may appear in the gross
ventilatory pattern, but the predominant defect usually remains restrictive in type.
Distributional abnormalities arise but are generally not severe, although variation
may be considerable. Pulmonary compliance drops appreciably and is ultimately
associated with a varying degree of hyperventilation or dyspnea and with a reduction
of total lung volume, including vital capacity, although the RV/TLC ratio sometimes
remains high. Diffusion abnormalities associated with the fibrosis are seen,
particularly if there is any sizable component of interstitial fibrosis or emphysema
present; under these conditions arterial oxygen undersaturation may be evident, espe-
cially with exercise. Hypercapnia is rarely observed, but if the extent of pulmonary
involvement has been great, pulmonary hypertension may be present to some degree.
In miliary tuberculosis, studies have confirmed that the main feature of the abnor-
mality is apt to be an increase in the alveolar-arterial oxygen pressure gradient,
sometimes in association with impaired membrane diffusion (see Fig. 26-8A). As
healing occurs, the physiologic picture of a diffuse fibrosis may appear. Bronchial
tuberculosis, if associated with partial obstruction to a major bronchus, will cause
some increased resistance to air flow, which is evident in the simple 1-second forced
expiratory volume and sometimes in an impairment of intrapulmonary gas distribu-
tion. Secondary local obstructive overinflation may occur and further affect these
functional abnormalities. If bronchial obstruction is complete, atelectasis will occur.
The continued perfusion of nonaerated portions of lung results in increased venous
admixture, but reduction in pulmonary blood flow 'occurs in the atelectatic lung over
a period of time and eventually the element of right-to-left shunt becomes negligible.
Pleural effusion or pleural fibrosis usually limits ventilation in a restrictive manner
much more severely than is ordinarily estimated by interpretation of the chest
roentgenogram. When these conditions occur, either during the course of pul-.
monary tuberculosis or as a complication of pneumothorax, the functional penalty is
great; after several years die loss of function may become permanent, although after
decortication sufficient time must elapse before the degree of recovery can be
properly evaluated.
In advanced predominantly unilateral tuberculosis, it is important to measure the
contribution each lung makes individually to the total functional derangement.
Bronchospirometry often strikingly demonstrates a lack of physiologic impairment
thought to be present after interpretation of the roentgenogram. The same information
may be obtained by using both ventilation and perfusion scan techniques and may
obviate the more uncomfortable bronchospirometry. Bronchospirometry and
scans may also clearly demonstrate the tremendous damage that tuberculosis may
produce in lung tissue. It is not uncommon for a severely involved lung to contribute
little or nothing to the total function. Such lungs frequently carry on a predominantly
dead space type of ventilation, and the absence of circulation can be further
confirmed by pulmonary arteriography. A very common finding is the coexistence of
tuberculosis and pulmonary emphysema of varying degree. This may influence or
complicate the functional pattern to the point that the contributions of the tuberculous
disease are difficult to recognize, unless the involvement is predominantly unilateral.
Extensive silicosis, often complicated by tuberculosis, may also produce severe
functional impairment.
Literature.
J. Crofton. Text book.