Ministry of Health of Ukraine
V.I.Petrenko
PHTHISIOLOGY
Textbook for IV level of accreditation establishments of higher education
Recommended by the Central Methodology Cabinet on Higher Education of Ministry of
Health of Ukraine as textbook for IV level of accreditation medical establishments of higher
education.
Editors: Professor Krizhanivsky D.G., M.D., Ph.D.
Professor Puhlik B.M., M.D., Ph.D.
Professor Pustovyi Y.G., M.D., Ph.D.
V.I.Petrenko. Phthisiology. Textbook.
Textbook contains history, epidemiology, etiology, pathogenesis and immunology of
tuberculosis. Highlighted are basic principles of diagnostics and treatment of pulmonary and
extrapulmonary tuberculosis as well as its prevention, work of dispensary and medical and social
expertise of temporary work leave. Special attention is given to measures of prevention of
tuberculosis in Ukraine and recommendations of World Health Organization for prevention of
tuberculosis.
Textbook is intended for students of IV level of accreditation medical establishments of higher
education and medical doctors.
DIAGNOSIS OF TUBERCULOSIS
Diagnostic work-up for patient with tuberculosis should include chief complaint, case
history, physical inspection, X-ray and laboratory testing. On the top of that anti-tubercular
dispensaries provide computed tomography, triple bacterioscopy and culture of patient’s sputum
for MBT and
its sensitivity to antibiotics. Bronchoscopy, pleural puncture and biopsy can be
performed sometimes to determine type and spread of disease as well as form differential
diagnosis with other diseases.
Case history.
Case history starts with finding passport data: first, last name and patronymic, age, home and
working address. Then they turn to complaints.
Complaints (chief symptoms). The earliest complaint a patient with tuberculosis will present
most often is weakness, easy fatigability and decreased capacity for work, low appetite, weight
loss and fever. These complaints are signs of intoxication. These symptoms are seen also in
different diseases of respiratory tract and are characteristic for pulmonary and extra pulmonary
types of tuberculosis; they may be seen in different combinations. Tubercular intoxication due to
activity of Mycobacteria diagnosis and accumulated products of protein degradation causes these
complaints. Such complaints as weakness, easy fatigability and decreased capacity for work, low
appetite, weight loss and increased perspiration patients with tuberculosis usually do not ascribe to
disease but rather with fatigue or physical overload.
Fever may vary. Patient with tuberculosis may have normal body temperature, or it can be
subfebrile and febrile. Patients usually do not feel they have fever and bare it well. In most cases
body temperature is normal or subfebrile (37-38.00C). Febrile (38-39.00C) and hectic (over
39.00C) body temperature is characteristic for acute onset or advanced forms of tuberculosis
(miliary tuberculosis, caseous pneumonia, acute pleuritis and pleural empyema).
Temperature chart is irregular, it is highest in the evening and normal in morning. In
rare cases a patient may have fever throughout the day.
Often patient will complain on higher perspiration of her head and chest mainly at night or
in the morning.
Profuse perspiration is seen in advanced types of tuberculosis (miliary
tuberculosis, caseous pneumonia). In these cases patient may have "rotten hey" foul smelling
sweat (Yanovsky F.G.).
Patient with tuberculosis may present with cough, sputum, chest pain, hemoptysis or
pulmonary bleeding, dyspnea . These complaints are characteristic of bronchial, pulmonary and
pleural involvement (broncho-pulmonary- pleural syndrome or "chest" symptoms) and dependent
on the type and location of tuberculosis.
Cough may be absent at the beginning of disease or may be hacking and unproductive
which does not bother patient. As disease progresses cough may increase, and in cases of fibrotic
and cavitary tuberculosis it may become exhausting and preventing a patient from sleep. Loud
cough is characteristic for patient with bronchoadenitis and tuberculosis of bronchi. Cough may
be dry (nonproductive) and wet with sputum (productive). At the beginning of disease of
respiratory tract there will not be any sputum. As disease progresses especially to formation of
cavities, the volume of sputum increases up to 200mlper day. At first it is clear, then mixed with
pus proceeding to suppurative only. In the beginning patient coughs up easily due to preservation
of function of ciliate epithelium, thus sputum moves to tracheal bifurcation and up. Due to lung
fibrosis structure of bronchi gradually deteriorates. Coughing up becomes more difficult.
Hemoptysis and pulmonary bleeding are seen mostly in cases of destructive types of
tuberculosis especially in cirrhotic lungs and in cases with central sclerosis of lungs and bronchi
with latter being difficult to recognize. In hemoptysis and pulmonary bleeding blood is bright red
and frothy and is seen only with cough. Diagnosis of hemoptysis and pulmonary bleeding is
facilitated by almost normal hemoglobin in common blood count (CBC) as not the case with
gastric and duodenal bleeding. This is because pulmonary bleeding is evident and usually patient
seeks medical attention right away. Depending on how massive bleeding is there is hemoptysis,
bleeding and hemorrhage (see chapter "Complications of tuberculosis").
Dyspnea is clinical symptom of respiratory and cardiovascular failure. It develops due to
failure of gas diffusion through alveolar membrane, decreased respiratory surface of lungs,
bronchial obstruction and toxic dysfunction of respiratory center in brain. At the beginning of
disease shortness is not marked (on physical exertion only) or even absent. It can be marked only
with miliary tuberculosis, pleuritis and caseous pneumonia. In case of progression shortness is
marked and bother patient even at rest.
Chest pain often is complained on at the beginning of disease. It results from pleural
involvement and focal pleuritis. Pleural pain is stabbing and is related to breath, cough and deep
breath make pain worse. Dull and constant pain is seen in chronic types of tuberculosis due to
pulmonary cirrhosis.
In case history proper it is important to find out for how long does patient have
complaints, course of disease and how the case was found (seeking medical attention due to
complaints or after fluorographic exam). Tuberculosis may have unnoticed, acute or gradual
beginning or it may begin under mask of other infectious disease. Small forms of tuberculosis
(focal, infiltrative, local disseminated and without pulmonary destruction) start unnoticed.
Subjectively patient feels well and only signs of disease are found on the X-ray film. It is worth
to notice that different forms of tuberculosis do not have their own clinical picture and take mask
of another disease at the beginning (influenza, pneumonia, cancer, typhoid fever, malaria, chronic
bronchitis, chronic keratoconjunctivitis, plexitis, radiculitis and heart failure with pain syndrome).
When these diseases take unusual course patient needs to be checked for tuberculosis. If
tuberculosis is not diagnosed for the first time then duration of disease and type of treatment
received have to be specified.
In history of life we specify presence of diabetes mellitus, gastric or duodenal ulcer, HIVinfection, traumas and operations. Pregnancy, delivery and especially abortion cause endocrine
changes in the body and thus may trouble provoke exacerbation of tuberculosis. The job and
possible congressional hazards, living conditions have to be recorded as well as smoking habits,
alcohol and drug intake and imprisonment if any. Latter adversely influence the body defense and
may promote or exacerbate tuberculosis.
Physical examination.
Patient with tuberculosis most often is quite active. Only in case of generalized chronic
tuberculosis and advanced disease patient is passive (for instance tubercular meningitis).
General exam reveals traces of tubercular intoxication: weight loss, pale and moist skin
and pale visible mucosa. Patients may have unhealthy eye blaze, wide pupils and hectic face flush
as result of irritation of simpathic nerve system due to tubercular intoxication. "Clock-face"
fingernails or "drum stick" shaped distal fingers could be seen in case of chronic disease or when
tuberculosis is complicated with amyloidosis. Skin of tuberculosis patient usually is pale red but it
also may be cyanotic especially in cases of generalized disease.
One has to record chest shape, its symmetry when breathing and localization of visible
pulsation. Fibrotic and cirrhotic stage of disease result in decreased lung and corresponding part
of the chest making affected side narrow and leaving it behind during respiration. This can deepen
supra- and subclavicular fossae, shift of heart pulse towards affected side and pulmonary artery
pulsating to the left of sternum. Narrow or wide intercostal spaces have to be recorded as well.
Palpation finds elasticity and moisture of skin, subcutaneous fat thickness and muscle
tone.
Most patients with tubercular intoxication will have cold moist palms. In cases of
generalized pulmonary tuberculosis associated with hypoxia patient's hand can be dry, warm and
cyanotic. Perspiration bothers patients most at night during sleep; they may have foul smelling
sweat ("rotten hey", Yanovsky F.G.). Skin elasticity at the beginning of tuberculosis will be
unchanged. Only exhausted patient with long standing tubercular intoxication skin elasticity is
low; subcutaneous fat is thin or absent. in adult tuberculosis causes gradual muscle atrophy, low
tone and pain on palpation. This is characteristic in palpation of upper border of trapezius muscle
on an affected side (Pottenger's sign).
Axillary’s and neck lymph nodes have to be examined meticulously because these are
most often affected with tuberculosis. Other affected lymph nodes available for palpation may
include mesenteric and rarely inguinal. Micropolyadenia may be seen in pediatric age. Lymph
nodes in posterior triangle of the neck are affected most often.
Vocal fremitus is most useful method of palpation. Vocal fremitus is transmitted well on
saying words containing "r" sound. Vocal fremitus is week or absent in cases of lung emphysema,
atelectasis, exudative pleuritis, pneumothorax and it is increased in infiltrated and fibrotic lungs.
Trachea shifts to affected side due to unilateral lung cirrhosis, which can be estimated by "fork
test" described by G. Rubenstine when one finger is placed over sternum’s manubrium and
another over trachea.
Percussion. Percussion sound is clear pulmonary over healthy lung because it is elastic
and air filled. Tympanic sound will be characteristic for pulmonary emphysema that develops in
disseminated, fibrotic and cavitary and miliary pulmonary tuberculosis. Tympanic sound will be
present over large cavities 4 cm in diameter or larger.
Dull sound on percussion will signify absence of air in lung or its decreased
pneumatization in infiltrate, atelectasis, and focal fibrotic changes and in cases of exudation
pleuritis. Subpleural pathological changes over 4 by 4 cm in size are found on percussion most
readily. Most often percussion sound will be dull over cavity because air in lung around cavity is
absent due to fibrosis and infiltration.
In secondary tuberculosis pathological changes localize in upper segments of lung in most
cases. Thus lung apex decrease in size and their height over clavicles can be less then normal 4
cm; width of Krenig fields is also decreased.
Auscultation. Tuberculosis is infections disease thus physician should position himself at
the side of the patient on auscultation. Patient should breath through semi-opened mouth and
cough quietly as doctor asks the patient to do so at the end of exhalation. There are sites of
Auscultation for lungs. Because tuberculosis affects mostly upper areas of lungs auscultation of
super-and subclavicular areas should be performed carefully: sites above scapula and below
clavicle are considered an "alarm zone". There are also cites of auscultation at 4th intercostal
space up front, 2nd and 5th- 6th auxillar intercostal space, below scapula in the back and in
paravertebral space at the middle of scapula.
"Vesicular" sound is auscultated over healthy lung. Different pathology may produce
different breath sounds and rales. Weakened breathing is auscultated over areas of atelectasis,
emphysema, exudative pleuritis, thickened pleura, pneumothorax and obesity. Amplified
breathing is auscultated over infiltrated lungs and in weight loss. Breathing becomes coarse in
focal fibrotic lung and it is bronchial (or amphoral) in case of giant cavities in lung. Rales are only
auscultated over diseased lung and are sign of activity of tuberculosis. Dry rales are most often
found when bronchi are affected. In cases of exudation, lung infiltration and in caseation there
will be wet rales of different caliber. In many types of tuberculosis especially during antitubercular therapy breathing may be unchanged and rales absent. These types of tuberculosis are
called non-auscultative types of tuberculosis. Then rales often may be auscultated only on the
height of inhalation. Local (focal) rales are characteristic for most types of tuberculosis. Pleural
murmur is auscultated in case of fibrotic pleural inflammation.
Study questions.
1. What complaints of patients are characteristic for tubercular intoxication?
2. What complaints of patients are characteristic for broncho-pulmonary-pleural symptoms?
3. What data should be collected for case history of tuberculosis patient?
4. What are "masks" of tuberculosis?
5. What signs of tuberculosis can you find at general exam of patient?
6. What are "alarm zones"? In what areas of lungs are they located?
7. What rales are called "local"?
8. What auscultation phenomena can do find in patient with tuberculosis?
9. What are Auscultation signs of cavity?
10. What is cause of pleural murmur?
Hematological Study.
Intoxication and hypoxia cause changes in the blood of patient. Oxygen is transported by
hemoglobin in erythrocytes. At the beginning stages of tuberculosis there are no changes in
erythrocytes function until failure of gas exchange. Progressing tuberculosis leads to failure of gas
exchange and hyperchromic anemia (increased hemoglobin level in decreased number of
erythrocytes).
Changes in leucocytes are more marked in tuberculosis. Acute disease causes leucocytosis
up to 10-14 x 10^9 / L, increased number of band forms and monocytes and decreased
lymphocyte count. Patient with advanced types of tuberculosis is usually lymphopenic.
Increased erythrocyte sedimentation rate is especially characteristic for tuberculosis. Like
in any inflammation, in tuberculosis products of protein degradation enter blood stream and then
absorb on the surface of erythrocytes. Erythrocytes lose their similar charge, paste together and
settle down faster. Decreased viscosity of blood promote increased erythrocyte sedimentation rate.
Blood biochemistry.
Biochemistry tests function of internal organs, certain stages of exchange and activity of
tuberculosis. Tubercular inflammation is associated with production of free radicals leading to
damage of cell membranes and release of mediators of inflammation (histamine, serotonine,
kinins, prostoglandines, leukotriens) and proteolytic enzymes from bacteria, leucocytes and
macrophages acting destructively in the focus of tubercular inflammation. Human body fights
these with system of proteins, which depress release of mediators of inflammation. These proteins
are synthesized in liver and are called proteins acute phase proteins: C-reactive protein, fibrinogen
B, haptoglobin, ceruloplasmin, and alpha1-antitripsin. Because most acute phase proteins are
glycoproteins there is simultaneous increase of carbohydrates (structure components of proteins)
in blood: syalic acid and hexosa.
Liver transforms most proteins. Since hepatocytes are
responsible for that free forms of medication may accumulate in liver leading to toxic damage to
it. Isoniazid, rifampin and pyrazinamide affect negatively the liver function, especially in case of
excessive
alcohol
intake.
Hepatocytes
damage
is
estimated
by
elevation
of
alanynaminotransferase (ALT) and aspartataminotransferase (AST): their elevation twice as high
as normal suggests advanced toxic hepatitis.
Failure of gall excretion (cholestasis) is estimated by elevation of gall components in
blood (direct bilirubin, alkaline phosphatase, betta-lipoproteins). If these gall components increase
while transaminases remain normal it is sign of cholestasis; elevation of both gall components and
transaminases is sign of toxic hepatitis.
Kidneys are another organs, which control tolerance to specific therapy because most
drugs are transported through kidneys. Such anti-tubercular medication as streptomycin,
kanamycin, amikacin, florimycin and kapreomycin are specifically nephrotoxic. For this reason
urine excretion of protein should be estimated; normally not present in urine organ specific
enzyme transaminase may appear even earlier then that. later kidney failure may develop which is
characterized by elevation of urea, creatinine and residual nitrogen.
Advanced tuberculosis with intoxication is associated with depletion of adrenal cortex.
Adrenal cortex depletion is estimated by decrease of glucocorticoids, 17-oxycorticosteriods and
aldosterone in blood and urine.
Important role in host' response to tuberculosis belongs to universal regulatory system of
eicosanoids. Eicosanoids of different types like prostaglandines, thromboxanes and leukotriens
influence function of vessels and their permeability, bronchi and humoral and cell-mediated
immunity (Petrenko V.I.). Type of failure of eicosanoid system depends on how general and
advanced is tuberculosis.
Study questions.
1. What causes changes in blood of tuberculosis patient?
2. What causes hyperchromic anemia in tuberculosis patient?
3. What changes in common blood count are characteristic for patient with tuberculosis?
4. What proteins depress release of biologically active substances?
5. What changes in blood biochemistry suggest hepatocytes damage?
6. Increase of what substances suggests failure of gall production in liver (cholestasis)?
7. What changes in blood biochemistry suggest kidney failure?
8. In what process takes part the system of eicosaniods in tuberculosis patient?
9. What eicosaniods influence on?
Laboratory testing for Mycobacteria
Sputum is mixture of secretion from mucosal glands from trachea and bronchi, serosal
transudate from damaged vessels, caseation particles, necrotic granulation and pulmonary
tissue and admixture of mineral salts. Sputum is delivered in many diseases of lungs and bronchi.
At the beginning of tuberculosis there is no sputum. As disease progresses volume of
sputum increases from several milliliters in the morning up to 100-200mlwith advanced disease.
Collection of sputum requires control of conditions, rules, adequate containers and safety of
medical personnel.
Conditions of sputum collection. To prevent spread of disease sputum has to the collected
by designated personnel in well-ventilated room (with windows opened) or outside on the territory
of medical institution. Ideally sputum has to be collected in especially designated room.
Collection of sputum in small inadequately ventilated rooms (restrooms) is prohibited. Collection
of sputum in the hospital should be performed in especially designated room at the presence of
nurse; collection of sputum at home should be done by the window.
Rules of sputum collection. sputum collection is performed in the morning after getting up.
patient should wash his mouth but should not brush his teeth because this can cause cough and
sputum will not be collected into the container. To collect sputum from lower respiratory tract
patient should make two slow deep breaths in and out holding his breath for 5 seconds to
facilitate maximum lung expansion. After that he has to take another slow deep breath in and out.
Then patient takes fast deep breath in and fast breath out to facilitate elevation of diaphragm.
Only such exhalation will cause natural cough. Sputum specimen should be no less then 2 cc.
Container for collection of sputum should be made of dense waterproof material. Its
opening should be no smaller then 35 mm to allow collection of sputum without infecting its outer
surface. The volume of container should be 20-50 cc. Container is made of transparent material
to be able to appreciate the volume of sputum without the of opening the container. Lid of
container should close tightly to prevent spread of the disease. One can use such universal
container as glass transparent bottle of corresponding size. Such container can be reused after
thorough sterilization. Volume of collected sputum should be 3-5 cc.
Classical method of laboratory testing of sputum is microscopy of smear and sputum
culture. Identified MBT are always tested for their sensitivity to antibiotics.
Bacterioscopy includes direct bacterioscopy of Ziehl-Neelsen stained specimen, flotation
bacterioscopy and phase contrast microscopy. Bacterioscopy of sputum starts with preparation of
smear.
For this sputum is mixed with sodium hydrooxide and worked in centrifuge until
formation of sediment which then is placed under microscope with glass rod. Mycobacteria are
Gram-positive. In order to find Mycobacteria smear is dried, fixed over flame and stained after
Ziehl-Neelsen. Staining starts with carbolic solution of fuchsine. Mycobacteria are not easily
stained thus large amount of fuchsine is applied and warmed over flame until evaporation.
Then dye is removed and preparation is washed in water followed by un-dyeing with 5%
sulphuric acid. This leads to un-dyeing of all bacteria and morphological
elements of sputum
besides MBT. smear is then wash with running water and then worked with methylene blue for 12 minutes. Preparation is then washed again, dried and placed under microscope immersion
system.
for that one drop of olive or ricin oil is placed over smear to create similar medium
between objective lens and smear. Red stained MBT are seen under the microscope. (Fig.1.15).
Weakness of bacterioscopy is its capability of finding MBT only when 1 cm 3 includes
about 5000-10000 bacilli provided that 300 power fields were examined. Bacterioscopy will not
be effective when number of MBT in smear is small.
Figure 1.15. Sputum smear preparation. Ziehl-Neelsen stain.
Examination of sputum should be performed three days in a row. Method of flotation can be used
under necessity (from floter (French) - move on a surface of liquid, or fluctuo (Latin) - to surface
the waters).
Method of flotation is based on flotation of lighter liquid with MBT when mixed with
heavier liquid. Water suspension with sputum is mixed with hydrocarbon solution (ksylol, bensol
which have smaller weight then water). Shaking this suspension will produce cream-like full
foam with MBT, which is then placed under microscope. When first layer is dry another one is
placed over it up to 5-6 layers placed one over the other. smear is then stained after Ziehl-Neelsen.
Even more effective method of finding MBT is luminescent microscopy when dyed with
special ultraviolet- sensitive dyes (auramine, rodamine). Strength of method is its ability to see
bacilli under smaller magnification and thus more power fields can be examined in shorter time
when compared with conventional bacterioscopy. It is 10-15 % more effective than conventional
microscopy and 8% more effective then flotation microscopy. Luminescent microscope is used
with small magnification: golden yellow MBT are seen on dark field.
Phase contrast microscopy is the only method of microscopy allowing studying
Mycobacteria and their forms alive. Phase contrast equipment is use for that purpose.
Cytology of sputum reveals degenerate neutrophils, caseation detritis, mononuclears, giant
Pirogov-Langhans cells and eosinophils in patient with pulmonary tuberculosis. With scant
sputum patient is prescribed with expectorant or study his bronchi wash.
Physician performs bronchial wash. After local anesthesia of tongue and back of throat
with 1 % dicaine 5-10mlof saline is instilled into trachea causing patient to cough up his sputum
along with instilled saline. Sometimes bronchial wash is performed along with bronchoscopy.
This method allows finding MBT in additional 5-10% of cases.
In clinical practice MBT are looked for in urine, feces, cerebrospinal and pleural fluid. Urine is
studied for MBT in cases when each power field contains at least 15 leucocytes. For that
urine is worked in centrifuge and placed in layers under microscope followed by Ziehl-Neelsen
stain. When MBT are found in urine a kidney tuberculosis is diagnosed.
Faeces should be studied for MBT when bowel tuberculosis is suspected. One has to
remember that patients may ingest their own sputum with Mycobacteria which then can be found
in faeces from healthy bowels because MBT are not always killed in digestion.
Finding of MBT in cerebrospinal fluid plays decisive role in diagnosis of tubercular
meningitis. Bacterioscopy can find tubercular meningitis in only 10-20 % of patients.
Cerebrospinal fluid is left in cool place for 8-10 hours. Slander fibrin film consisting of cells and
MBT is formed after this time and then examined under microscope after Ziehl-Neelsen stain.
When film is not formed then cerebrospinal fluid is worked in centrifuge.
Pleural exudate, punctates and fistula contents is prepared the same way as sputum.
Bacteriological examination is culture of specimen on nutrient media. This method is
useful when 1mlof specimen contains 20-100 bacilli. Test tubes with nutrient media are placed in
thermostat with temperature of 370C. First colony may be found on 18-30th day, and sometimes in
2-3 months. Bacteriology examination is done along with bacterioscopy three times.
Specimen most often is cultured on one of egg media (Petraniani, Lubenay-Gone,
Levenstein-Yensen) containing dyes, which prevent growth of other microbes. Killing of
concomitant bacterial flora in specimen precedes culture. Bronchi and urine specimen are worked
in centrifuge. Uncontaminated urine may be left without previous preparation.
Biological method is inoculation of specimen to animals. Guinea pigs or white mice are
inoculated into inguinal area or peritoneal cavity with 2-3ml of specimen after disinfection with 38% solution of hydrochloric acid followed by proper wash (skin necrosis or even death might
result when skin is not washed well). Uncontaminated urine or cerebrospinal fluid can be
inoculated without preceding disinfection. Animals contract tuberculosis and die in 1-2 months
after inoculation when specimen contained virulent MBT.
When Mycobacteria are weakly
virulent animal dies later or remains alive. In such cases animal is sacrificed and its tubercles are
examined under microscope. Tuberculosis can be also diagnosed by bioptates of enlarged lymph
node or infiltrate at the site of inoculation.
BBL MGIT (Mycobacteria Growth Indicator Tube) is method of accelerated testing for
tuberculosis, which takes 4-10 days to grow. Testing tube contains growth media and oxygensensitive fluorescent dye. The result is positive when bright fluorescence is seen on the tube’s
bottom due to consumption of oxygen from media by MBT. The result is negative when
fluorescence is weak or absent. The result in accounted for daily starting from second day of
incubation.
Mycobacteria strains are differentiated by gas chromatography, which is capable of
differentiating between amino acids, nucleic acids, lipids and carbohydrates. Weakness of this
method is that Mycobacteria still have to be cultured on nutritive media.
Other experimental methods of Mycobacteria identification include using over 100
monoclonal antibodies against basic antigens of M. tuberculosis and M. bovis.
DNA-probe and polymerase chain reaction methods most often used among molecular
genetic methods of diagnostics of tuberculosis. These methods are based on complimented
nucleotide bases in double spiral of DNA. These highly sensitive methods allow identification of
up to 10-100-1000 bacilli in specimen in as short as 2-4 days. Polymerase chain reaction is based
on amplification of Mycobacterium’s DNA due to building it up to 106 times by DNApolymerase. Positive result is found by electrophoresis under ultraviolet light.
Study questions.
1. What sputum consists of?
2. What are rules for collection of sputum?
3. What other specimens can be collected from tuberculosis patient other then sputum?
4. What is method of bronchi wash?
5. What are methods of examination of sputum for MBT?
6. What is flotation method?
7. What is luminescent microscopy?
8. How long does it take for MBT to grow on nutritive media?
9. How many MBT should 1 ml of sputum contain for successful diagnosis with
bacterioscopy and culture?
10. What are methods of accelerated identification of MBT?
TUBERCULIN DIAGNOSTICS.
Tuberculin diagnostics is most widely used for identification of reaction of the host to
infection with MBT or BCG vaccination. Tuberculin diagnostics is specific, which means that
only infected host will react. Tuberculin skin test is classical immunology test. It is performed
with tuberculin.
R.Koch received first tuberculin in 1890 (ATK-alt tuberculin Kochi, or old tuberculin of
Koch). This tuberculin had much ballast substances from nutritive media where Mycobacteria
were grown. These proteins from media could cause non-specific reactions when used in skin
testing.
More specific tuberculin, free from ballast substances of nutritive media was made by
F.Seibert and Glenn in 1934 and was called purified protein derivative standard (PPD-S). PPD-S
was accepted as international standard in 1952. In former Soviet Union M.A.Linnikova received
purified tuberculin in 1939 (PPD-L).
Tuberculin is complex of proteins, polysaccharides, lipids, nucleic acid, and remains of
MBT and products of their metabolism. Tuberculin is not complete antigen (hapten) because it
cannot sensitize the host to cause it to produce specific antibodies. It only is capable of revealing
the immunological response in sensitized host. It is valuable product because only infected host
will react; thus tuberculin test is specific. Tuberculin is produced in 3ml ampoules each containing
30 doses. Activity of tuberculin is measured in tuberculin units (TU). 1 TU is the least amount of
tuberculin capable of causing reaction in infected host. Intensity of such reaction depends on
massiveness and virulence of Mycobacteria as well as upon sensitivity and reaction of the host.
Tuberculin reaction can be absent (anergy), weak (hypoergy), moderate (normergy), and
pronounced (hyperergy). Anergy may be positive when the host is not infected and in patient with
advanced tuberculosis. Different factors like bronchial asthma, rheumatic fever, pneumonia,
scarlet fever, tonsillitis, cholecystitis, sinusitis, influenza, and hypothyroidism can increase
tuberculin sensitivity. Antihistamines, corticosteroids, vitamins B,C,D, burns, polio vaccination
may decrease tuberculin sensitivity. Tuberculin sensitivity increases in spring and decreases in fall
due to saturation of the host with vitamin C acting as natural antihistamine. Thus tuberculin skin
test should be done in the same time of the year not earlier then 1 month after any vaccination.
PPD-S is international standard. 1 TU contains 0.00002mg of PPD-S, and PPD-L contains
0.00006 mg.
Mantoux intradermal test (introduced by French scientist S. Mantoux and German
scientist Mendel in 1909) and subcutaneous test of Koch are used in our country today. Mantoux
skin test is used for the following purposes:
-
Early diagnosis of tuberculosis (non-localized infection, i.e. tubercular
intoxication) in children and teenagers.
-
Epidemiological study of infection in population.
-
Case find for revaccination.
-
Finding of persons under increased risk of clinical disease (primary infection,
hyperergic reactions).
Annual Mantoux skin test is performed by disposable tuberculin syringes with 2 TU in
0.1ml of PPD-L starting from the first year of life independently of previous results of this test in
the absence of contraindications.
Contraindications for Mantoux skin test are:
-
Acute and exacerbations of chronic infectious diseases.
-
Cases before 2 months after recovering from an infectious disease.
-
Skin diseases.
-
Allergies (rheumatic fever, bronchial asthma).
-
Epilepsy
-
Birth traumas.
Mantoux skin test is performed as follows: both tip of ampoule with tuberculin and skin of
volar forearm is disinfected with ethyl alcohol. Ampoule is opened and 0.2 ml of tuberculin is
collected into syringe. Upward leveled needle is inserted in parallel fashion just beneath the
prepared skin. Then 0.1 ml of tuberculin is delivered causing “lemon skin” papule (Fig.1.16).
Figure 1.16. Tuberculin skin test technique.
Mantoux skin test reveals slow type hypersensitivity reaction. It is explained by migration
of sensitized T-lymphocytes, macrophages with antibodies to the site of inoculation with
tuberculin (incomplete antigen). Due to antigen-antibody reaction destroyed cells release
mediators of inflammation causing such local inflammatory reaction as hyperemia, infiltrate or
pustule (vesicle). Mantoux skin test site is read in 72 hours for diameter of infiltrate (measured
perpendicular to forearm length) or when absent, for diameter of hyperemia. Mantoux skin test is
estimated as in Table 1.2.
Table 1.2. Mantoux skin test reaction for 2 TU PPD-L.
Diameter of infiltrate
Character of reaction
0-1 mm
Negative
2-4 mm or hyperemia only
Doubtful
5 mm and more
Positive
17 mm and larger in children
21 mm and larger in adults
Any diameter of infiltrate in presence of
vesicle, necrosis with or without lymphangitis
Hyperergic
Mantoux skin test reaction for 2 TU is used to find virage (positive reaction) suggesting
infection of the host.
Virage – is early period of primary tuberculosis found on the ground of infectious allergy
but absence of local signs of tuberculosis. Virage can be described as
a. Negative Mantoux skin test turning positive.
b. Increase of post-vaccination Mantoux skin test by 6 mm or more.
With obligatory BCG (re)- vaccination Mantoux skin test reveals infectious and postvaccination immunity. Post-vaccination Mantoux skin test has following characteristics:
-
Maximal diameter is found on the first year of life.
-
Diameter of infiltrate is less then 12 mm.
-
Mantoux skin test reaction decreases annually to negative by 5-6 years of age due
to decrease of immunity.
-
Infiltrate does not last long and disappears in one week without pigmentation.
Subcutaneous tuberculin Koch test was introduced by R.Koch in 1891. It is used for:
-
Differential diagnostics of tuberculosis.
-
To estimate activity of tuberculosis.
This test is used rarely today due to availability of more informative up-to-date testing.
Subcutaneous tuberculin Koch test is performed as follows: 20-50 TU of tuberculin is
injected subcutaneously at the lower angle of scapula. Reaction can be local, general and
focal depending on the dose of tuberculin and condition of the host.
Local reaction reads as infiltrate 10-20mm in size appearing in 72 hours. General
reaction develops as fever and weakness in 6-12 hours after subcutaneous injection of
tuberculin. Focal reaction is exacerbation of tubercular inflammation in lungs as perifocal
infiltration around tubercular foci. In pulmonary tuberculosis focal reaction can lead to
exacerbation of caught, increase in sputum production, chest pain and hemoptysis. There
are also modifications of Koch’s reaction, which provide additional information; these
require common blood count, serum protein and immunity testing.
Tuberculin injection increase leucocyte count (by 1000 and more) and ESR (by 3
mm/h) and decrease in lymphocyte count (by 10 cells). Serum α1 and α2 globulin fractions
are found to be increased and albumins decrease by 10%.
Study questions.
1. What is tuberculin?
2. What preparations are sued for tuberculin diagnostics?
3. What are indications for Mantoux skin test with 2 TU PPD-L?
4. What reactions may tuberculin cause in the host?
5. What is the purpose of tuberculin diagnostics as mass screening method?
6. What is measured in reading of Mantoux skin test?
7. How results of Mantoux skin test with 2 TU PPD-L are read?
8. What is “virage” of tuberculin skin test?
9. What does positive Mantoux skin test with 2 TU PPD-L is indicator of?
10. What is contraindication for tuberculin tests?
Immunology testing for tuberculosis
Immunity of the host is tested by number, function of immune competent cells and
intensity of their specific response to allergen (tuberculin). Main purpose of immunology testing
is revealing of failure of one or another link of immune system. Most tuberculosis patients are
found to have the following changes in their immunity:

decrease in number of T-lymphocytes and their capability for proliferation;

change of helpers, suppressors, killers ratio;

dysfunction of B-lymphocytes (increase or decrease of contents of B-cells,
dysimunoglobulinemia, decrease in number of natural antibodies);

failure of phagocytes (decrease or increase in their phagocytosis, adhesion, migration
and activity of cell enzymes), activation of specific cell and humoral reactions (Table
1.3.)
Table 1.3. Main changes of immune system in tuberculosis (Chernushenko K.F., 2003)
Non-specific
Specific
T-lymphocytes (T-lph) - decrease in number of T-lph - increase of sensitized T-lph
- change of Th/Ts
- increase of proliferation of
- decrease of proliferation of
T-lph in response to specific
T-lph in response to nonallergens;
specific mitogens (FGA,
- activation of enzymes in TCon-A, LM)
lph in response to allergens
- activation of enzymes
B- lymphocytes (B-lph) - change (most often increase) - increase in number of specific
in number of B-lph
antibodies to IK
- decrease in number of natural
antibodies;
- dysimunoglobulinemia (IgM,
IgG, IgA, IgE)
Different types of tuberculosis produce different intensity of abovementioned changes,
which depend also on intoxication, duration of disease, presence of destructive changes and
massiveness of bacterial seeding. Immunological diagnostics of tuberculosis patient includes
reading of local reactions. For this purpose bronchial lavage or pleural exudate are examined for
such parameters as number of cells, their structure and viability, functional activity of alveolar
macrophages and neutrophils and humoral factors (secretory Ig-Sig, lysozyme). Tuberculosis does
not change number of cells in bronchial lavage, moderately decreases their viability, but it does
change cell ratios due to decreased alveolar macrophages and lymphocyte and increased
neutrophils count. Migration, adhesion and phagocytosis function of phagocyting cells decrease
along with increased oxygen-dependant metabolism and activity of cell enzymes. These factors
depend on extent of pulmonary tuberculosis.
Lately immunoenzyme essays were introduced for detection of anti-tubercular antibodies.
Immunological testing can be for estimation of effectiveness of treatment of extent of
recuperation of patient. One may note dynamics of immunology testing before, during and after
treatment. Most patients improve their immunology profile and some have it normalized. Longterm failure of immunological improvement may suggest the need for immune correction with
appropriate medication.
Radiological Diagnosis
Radiography Diagnosis
Phthisiology uses radiography, ultrasound, magnetic resonance and radioisotope scanning.
Primary method used for diagnosis of tuberculosis is radiography: it helps determination
of type, localization of disease as well as its differential diagnosis and helps to keep track of its
progress to estimate effectiveness of therapy.
Among radiography methods are: fluorography, roentgenography (X-ray), roengenoscopy,
tomography, computed tomography (CT). Sometimes they use radiography with contrast, such as
bronchography, fistulography, angiopulmonography and pleurography.
Roentgenography (X-ray) and roentgenoscopy are used to determine chest shape, lucency
and width of lungs, localization and sizes of mediastinal organs. Roentgenoscopy helps estimation
of diaphragmatic and anterior costal movements.
Chest shape may change due to fibrosis, cirrhosis, atelectasis which result in decreased
intercostal spaces and emphysema resulting in increased intercostal spaces. Exudative pleuritis
causes mediastinal shift to the contralateral side while atelectasis and sclerosis causes ipsilateral
mediastinal shift. Lucency of lungs reflects on alveolar aeration. All pathological processes
leading to decreased aeration also cause decrease in lucency of the lung. These include: specific
and non-specific inflammation, pulmonary tumors, atelectasis and congestion in pulmonary
circulation. Decreased lucency will be seen in cases of overweight and in pleuritis due to
thickened pleura.
Normally X-ray finds include pulmonary tree representing dichotomy of pulmonary
arteries and veins. Thus it is also called vascular tree (Fig.1.17) whose density may increase
(Fig.1.17A) or decreased.
Figure 1.17 Normal pulmonary tree
Figure 1.17A Increased density of pulmonary tree.
Chief features of tuberculosis on X-ray are focus, infiltrate, cavity, fibrosis, cirrhosis and
pleural exudate. They differentiate small (1-2 mm), medium size (3-6 mm) and large (7-10 mm)
foci, as well as foci of low, medium and high density (Fig.1.18, 1.19)
Figure 1.18. Large (100 mm) focus.
Figure 1.19. Total seeding with small foci of medium and high density.
Foci of 10 mm and larger are called infiltrates or tuberculomas. Small size foci are
characteristic of miliary tuberculosis, and medium and large size shadows are features of subacute
and chronic disseminated, focal and cavity tuberculosis. Fresh foci are less dense then old ones.
Dense foci have precise borders and irregular shape and are well visualized.
Most often primary tuberculosis affects apical (S1), posterior (S2) and anterior (S3), upper
segment of lower lobe (S6) and S4 and S5 segments. Secondary tuberculosis affects most often
S1, S2, S6 and it is rarely affects other segments.
Foci may be hidden behind clavicle, mediastinum, especially behind the heart and major
pulmonary vessels. Thus X-ray should be taken in different views and positions. Apical segments
are best seen with clavicles displaced upwards; medial and intrathoracic lymph nodes are best
viewed I lateral and oblique views (Fig. 1.20, 1.21).
Figure 1.20. Left lateral X-ray.
Figure 1.21. Right oblique anterior X-ray view.
Roentgenoscopy finds diaphragm moving in synchronic fashion with inhalation and
exhalation. Normally the depth of diaphragm excursion is 5-6 cm. Lung emphysema and sinus
obliteration decrease movements of diaphragm.
Fluorography. This method allows placing X-ray picture on a photographic film. Now
they use large-film fluorography(110x110 mm). Strength of this method is its suitability for
screening of large numbers of cases and lower costs. Weakness of method is more radiation to the
patient and doctor performing it.
Digital fluorography now substitutes film fluorography. Strengths of this method are high
quality and information yield due to capability of separate enlargement of any part of lung for
closer analysis and for higher contrasting, computed imaging, by 10-15 times lower radiation and
faster obtaining of image (in 10-20 seconds). Digital fluorography is used for screening and for
diagnosis of tuberculosis.
Roentgenography. This method allows to picture pathological changes in lungs. First,
anterior-posterior (AP) view is taken so that central ray is passing through sagital plane of the
patient with film situated at the front chest wall.
On X-ray, all densities are white and lucent lungs are black.
AP view is supplemented by lateral view, which helps localize pathological focus in
relation to roots, lobes and segments of lung, as well as its size. Effectiveness of treatment is
estimated by comparison of serial chest X-ray films.
Spot-film roentgenography. This method allows to specify details of pathological changes
in lungs.
Roentgenoscopy of lungs is rarely performed; it requires special equipment with
electronic optic transformer (EOT). Indications for roentgenoscopy are: control of precision of
spot-film X-ray, angiography, fistulography and pleurography. Roentgenoscopy allows
localization of pathological focus, its motility and relation to chest wall and mediastinal organs, as
well as diaphragmatic motion and condition of pleural sinuses. Its weaknesses are grater radiation
load for patient and physician and lack of documentation.
Tomography is used for X-ray examination in layers when minute details have to be
investigated in lungs. Films are taken for layers on different depth after each 1-2 cm. Variation of
tomography is tomography with different thickness of investigated layer. If X-ray tube is angled
by 100 or less then one will receive picture of wide zone, or “zonograph”. On zonograph one can
see more structures and their relation to one another. Most readily zonograph may find small foci,
cavities and caverns, because they are completely included into the investigated layer (Fig.1.22).
Figure 1.22. Tomography. Sections readily reveal root of lung and cavity.
When X-ray tube is angulated by 15-300 one will receive “thick” sections used to
investigate pulmonary vessels.
When X-ray tube is angulated by over 500 one will receive “thin” sections helping to find
thin cavernal walls, tumors, cysts, tuberculomas, round shadows, foci and emphysema bullas.
One-time multi-layer tomography allows receiving several tomography films (through all
thickness of lung) in one exposition. For this purpose they use special boxed films, or
simultaneous cassettes, which can be loaded with up to 7 films. Method is used for diagnostics of
disseminated tuberculosis and finding whether parenchymal destruction is present no found on
conventional tomograms.
Bronchography is method of contrast X-ray investigation of bronchi (Fig. 1.23). It is
more often used for investigation of bronchiectases, bronchial deformities and functional changes
to bronchi. Before this study patient is checked for iodine allergy. Contrast matter (sulfoiodol, or
iodlypol with thin powder of norsulfazol) is introduced into investigated bronchus under
roentgenoscopy control. Bronchography is performed on an empty stomach under sufficient
anesthetization of respiratory tract mucosa by spraying 1% dicaine on mucosa of nose, posterior
throat, epiglottitis and vocal cords. Additional 1 ml of 1% dicaine is introduced into trachea with
laryngeal syringe. Catheter is introduced through nose into bronchus, after which respective
bronchus is anesthetized with 5 ml of 5-10% novocaine. Overall no more then 5 ml of 1% dicaine
and 15 ml of 5-10% novocaine are used. Then 15-20 ml of norsulfazol is introduced. After
bronchography contrast matter is aspirated from bronchus followed by injection of 250 000 units
of penicillin and 0.2 g of streptomycin into trachea. Sometimes water- soluble contrast matters are
used abroad (Chirtrust) which are absorbed by mucosa and metabolized by kidneys. Since the
advent of computed tomography this method is rarely used.
Figure 1.23. Bronchography.
Angiopulmonography is method of X-ray investigation of pulmonary artery and its branches
(Fig,1.24), allowing to gather information about functional condition of pulmonary vessels in
different types of tuberculosis and other diseases. Angiopulmonography has limited indications; it
is used for diagnostics of pulmonary artery thrombosis or embolism.
Figure 1.24. Angiopulmonography.
Pleurogrpahy. In this method pleural cavity is contrasted. It is used in patients with
empyema to find borders of suppurated cavity or when broncho-pleural fistula is suspected.
Fistulography is used in cases of broncho-pleural fistulas. Fistula is injected with contrast
matter and X-ray is taken (Fig. 1.25)
Figure 1.25. Fistulography. Walled off cavity is contrasted.
Computed tomography allows receiving axial plane sections of the patient. X-ray tube
moves on a special installation around the long axis of patient. Thin X-ray bundle falls on the
patient under different angles and is detected by scintillating detectors moving in sync with the
tube. Different density of tissues between the tube and detectors causes intensity of X-ray bundle
to change, which is then processed by computer and transmitted into picture on a computer screen.
Thus computed tomography is not a conventional X-ray, but a computer-generated picture of
investigated part of the body, based on mathematical analysis of X-ray absorption ratio by tissues
of different density (Fig.1.26).
Figure 1.26. Computed tomography.
Computed tomography of the chest allows detailed localization and extension of all
pathological changes and to estimate their precise size, as well as to keep track of their dynamics
of change in size and density.
Magnetic resonance imaging
Role of magnetic resonance imaging in diagnostics of pulmonary diseases is under
investigation. This method is used more and more often; it allows contrasting fat tissue of
mediastinum, dense structures and vessels and allowing identification of pathological focus
without the need of injection of contrast matter. Weaknesses of magnetic resonance imaging
related to its inability to determine calcification and short duration of pulmonary imaging, which
significantly limits information about lung parenchyma.
Ultrasound imaging.
Ultrasound imaging is safe, well-tolerated method, which can be used multiple times in the
same patient, wide range of capabilities of ultrasound equipment and short duration of
examination. Ultrasound is used for detection of different pathology in organs and tissues due to
potent mechanical waves, which have no ionizing potential.
This method is used in phthisiology for diagnostics of pleuritis (empyema), differential
diagnostics of tumors, topical diagnostics of extrapulmonary tuberculosis, provision of safety of
punctures for diagnosis and treatment, and examination of internal organs in patients with
tuberculosis. Ultrasound is not used for diagnosis of pulmonary diseases because aeration of lungs
distorts borders of pathology.
Radioisotope Scan.
Complex radioisotope scan is used for estimation of functional condition of lungs. It
consists of dynamic radioisotope scan with gas and water soluble
133
Xe (Fig.1.27) and static
radioisotope scan used to estimate regional pulmonary blood flow based on microembolization of
pulmonary capillary blood flow by macroaggregated particles of human serum with
133m
99m
Tc,
131
I,
In.
Radioisotope scan is used mainly for detection of functional failure of regional pulmonary
blood flow and ventilation in adult patients. It is used for:
1. Control of effectiveness of antibacterial adjunct therapy;
2. To estimate the need and volume of surgical treatment;
3. To grade the risk of surgical intervention;
4. For estimation of postoperative pulmonary function.
Radioisotope scan is contraindicated in patients with hemoptysis, pulmonary bleeding,
fever and in pregnancy.
Figure 1.27. Radioisotope scan.
Study questions.
1. What radiological methods are sued for diagnosis of pulmonary tuberculosis?
2. What is pulmonary tree on X-ray?
3. What are features of tubercular inflammation on X-ray?
4. In what segments does primary and secondary types of tuberculosis localize?
5. What method allows for detection of movements of lower lungs?
6. What is principle of fluorography?
7. What is tomography?
8. What is the purpose for using tomography?
9. What is principle of computed tomography?
10. What is bronchography? What information does it provide?
Respiratory and cardiovascular function tests in a patient with tuberculosis
Function of different organs will need to be evaluated in a patient with tuberculosis.
Physical, radiological, laboratory and functional methods may provide necessary information.
Assessment of respiratory status
Main function of lungs is oxygenation and clearing of blood from of CO2 and other
metabolites. This process is called external breathing and it consists of:
-
Ventilation is transport of air through bronchi, bronchioles and alveoli;
-
Gas diffusion is penetration of oxygen to blood and CO2 from blood to alveoli;
-
Perfusion is circulation of blood in pulmonary circuit.
Chief goals of assessment of respiratory status seeks to find:
-
Type of ventilation failure;
-
Degree of bronchial patency failure;
-
Level of affected bronchi (major, medium, small)
-
Failure of elasticity of lungs;
-
Whether surgical operation is indicated.
Up-to-date computed spirometry testing is used for estimation of external breathing at rest
or after physical exercise, performed on an empty stomach preferably in the morning or after 1,5-2
hours past the last meal. Parameters of spirometry can be found in table 1.4.
Table 1.4. Parameters of ventilation.
№
1.
2.
3.
4.
5.
6.
7.
8.
9.
Parameters of ventilation, abbreviated
Ukrainian
International
ZhEL
VC
(Vital
(Vital capacity
capacity), L
of lungs), L
FZHEL
FVC (Forced
(Forced vital
vital capacity), L
capacity of
lungs), L
ОFV1
FEV1 (Forced
(Forced
expiratory volume
expiratory
at 1 s), L
volume at 1 s),
L/s
Index
of
FEV1 . 100%
Tiffneau
VC
(%)
PShV
PEF
(Peak
(Peak
expiratory flow),
expiratory flow), L/s
L/s
MOSh25
МEF25
(maximal
(maximal
expiratory flow, expiratory
flow,
25% of VC), L/s 25% of VC), L/s
MOSh 50
МEF50
(Maximal
(Maximal
expiratory flow, expiratory
flow,
50% of VC), L/s 50% of VC), L/s
MOSh 75
МEF75
(Maximal
(Maximal
expiratory flow, expiratory
flow,
75% of VC), L/s 75% of VC), L/s
ChOD
Explanation
Maximal expiratory volume of air after
deep breathe.
Fastest possible expiratory volume
after deep breathe.
Fastest
first
second’s
possible
expiratory volume after deep breathe.
Air speed in trachea and major bronchi.
Air speed in medium sized bronchi.
Air speed in small bronchi (smaller
then 2 мм in diameter)
Volume of air ventilating lungs at rest
10.
11.
(One minute
volume of
ventilation), L
MVL
(maximal lung
ventilation), L
KRD
(Coefficient of
breathing
reserve)
per minute.
Volume of air ventilating lungs at
maximal breathing frequency and depth
per minute.
Estimates how much can a patient
increase his ventilation under physical
exercise. KRD = MVL / ChOD
Most useful parameters are VC, FVC, FEV1, PEF, МEF25, МEF50, МEF75; other parameters are less
informative about ventilation.
Failure of bronchial patency is estimated by forced expiration curve (flow-volume curve):
PEF, МEF25, МEF50, МEF75, medium expiratory speed 25-75% (SOSh25-75), medium expiratory
speed 75-85% (SOSh75-85). Flow-volume curve can be found on figure 1.28.
Figure 1.28. Flow-volume curve.
Computer based equipment calculates due values of VC, FVC, FEV1, PEF, МEF25, МEF50,
МEF75 and compare them with actual measurements.
There are two types of ventilation failure:
-
restrictive type is characterized by decrease of VC by less then 80% of due value;
-
obstructive type is characterized by decrease of FEV1 by less then 70% of due
value , FEV1/VCx 100% is <70%.
Failure of patency of large bronchi is characterized by decrease of PEF and МEF25, medium
sized bronchi failure is characterized by decrease of МEF50,and failure of small size bronchi is
found by decrease of МEF75.
Mixed restrictive-obstructive type is based on simultaneous decrease of VC < 80% of due
value, FEV1 by less then 70% and FEV1/VCx 100% is <70% and decrease of speed parameters.
Function of ventilation is reflected by paused ventilation test. Stange’ test is performed in
sitting position when patient holds his breath at the height of maximal inspiration; lower threshold
for this test is 20 seconds. Gench-Saabrase test is performed at the end of expiration; lower
threshold for this test is 15 seconds.
Peak flowmetry measures peak expiratory speed in liters per second or minute to estimate
the degree of respiratory obstruction. Peak flowmetry provides full information about patient’s
condition, effectiveness of treatment and allows a patient to monitor course of disease on his own.
Peak flowmetry correlates with FEV1, which is used to estimate degree of respiratory
obstruction and resistance; latter is estimated by pletismography.
Pneumotachimetry measures inspiratory and expiratory airflow. Normal values are from 34 to 6-8 L/second; the greater then value the better, because that means absence of obstruction.
Respiratory failure is condition when blood oxygenation and CO2 metabolism are
inadequate. Ventilation function derangement and hypoxemia signifies respiratory failure. Normal
oxygen concentration (HbO2) is 96-98%. There are three degrees of hypoxemia: I degree is when
arterial oxygen concentration is decreased to 90%, II degree is when it is 89-90% and III is when
it is 79-60%. Oxygen concentration in blood characterizes respiratory compensation rather then
degree of respiratory failure. Thus oxygen saturation does not fully reflect on functional adequacy
of ventilation.
Assessment of cardiovascular status
Chief parameters of cardiovascular status are arterial pressure (AP), venous pressure (VP),
circulating blood volume (CBV), blood flow speed (BFS), and blood volume per minute (BVM).
Most often electrocardiography is used in phthisiology.
Cardiovascular failure in tuberculosis is associated with intoxication and right heart
overload and hypertrophy. Tuberculosis patient is often diagnosed with sinus tachicardia,
(especially during exacerbation of chronic tuberculosis), and myocardial hypoxia. QRS complex
may manifest indentation. According to G.Vidimsky chronic congestive heart failure is
characterized
by
the
following
direct
and
Direct features:
1. R wave is > 5-7 mm in V1;
2. R/S in V1 is > 1;
3. RV1 + SV5 is > 10,5 мм (Sokolov Index);
4.
Right heart overload in V1—V 2.
Indirect features:
1. R wave in V5 is < 5 мм;
2. S wave in V5 is > 5 мм;
3. R/S у V5 is < 1;
4. R/S in V5 and R/S in V1 is < 10 (Salazar-Soddi-Palares index);
5. Pulmonary waves in РII—PIII;
6. SI—SII—SIII type;
7. Deviation of electric axis of the heart to the right.
indirect
features:
Echocardiography (EchoCG) is ultrasound evaluation of the heart. EchoCG may allow
accurate qualitative and quantitative estimation of cardiovascular failure due to pulmonary
diseases, including tuberculosis. This highly informative method allows detection of pulmonary
hypertension even before other methods like physical exam or ECG will detect it. EchoCG may
accurately estimate degree of hypertrophy and dilation of heart chambers as well as congenital
and acquired valve defects.
EchoCG data on function of right atrium and ventricle is important in phthisiology. Increased
pressure in pulmonary artery is estimated by degree of tricuspid regurgitation (that is backward
blood flow from right ventricle to right atrium through tricuspid valve during systole). Systolic
pressure can be measured in pulmonary artery even in minimal tricuspid regurgitation present in
almost all patients with pulmonary hypertension and in most healthy persons. Maximal speed of
retrograde blood flow allows calculation of trans-tricuspid gradient (difference of pressure in right
ventricle and atrium in systole) by Bernoulli equation. Sum total of trans-tricuspid gradient and
pressure in right atrium equals the systolic pressure in pulmonary artery. Right atrium pressure is
5 mmHg provided that diameter of vena cava inferior decreases by 50% during deep breathe;
when diameter of vena cava inferior decreases by less then 50% during deep breathe then 15
mmHg is considered a normal right atrium pressure. Thus,
Pressure in pulmonary artery = Pressure in right atrium+ Trans-tricuspid gradient
Instrument aided diagnostics
Bronchoscopy is most often used among other methods of instrument aided diagnostics of
tuberculosis.
Fibrobronchoscopy is performed under suspicion of tuberculosis, cancer of trachea or bronchi,
polyps, adenoma, ulcer and stenosis of bronchus. Diagnostic bronchoscopy allows for bronchial
wash and biopsy of bronchial mucosa, lymph nodes puncture of the root of lung and mediastinum.
Bronchoscopy is used to improve incomplete atelectasis and to aspirate mucus and foreign bodies
from bronchi, bleeding vessel coagulation, bronchial sanation and lavage.
Performed under local anesthesia, bronchoscopy allows for inspection of trachea, bifurcation,
main and lobar bronchi, and openings of segmental bronchi.
Technique of bronchoscopy under local anesthesia is as follows. Bronchoscopy is performed
on an empty stomach. 10% lidocaine is sprayed from laryngeal syringe on tongue root, posterior
wall of the throat, epiglottis and vocal cords. 1ml of 10% lidocaine is instilled into trachea before
introduction of bronchoscope for inspection of larynx, trachea and bronchi.
Bronchoscopy allows for bronchial and alveolar lavage (BAL) to receive bronchial and
alveolar liquid for studies of pulmonary cells. BAL is performed at the level of segmental and
sub-segmental bronchi of medial lobe or S3 at the right. Catheter is introduced through
bronchoscope into bronchi of 5-6 order for their occlusion. 20ml of isotonic saline is instilled 5-8
times (total of 100,0 ml) into catheter. Bronchial and alveolar wash is aspirated through catheter
for chromatographic testing for contents of lipids and phospholipids. Basic lipid fractions are
found to be altered in patients with tuberculosis.
Methods of biopsy. Biopsy is widely used today during bronchoscopy (Fig.1.29).
Figure 1.29. Types of biopsy (Perelman M.I., 1990).
1- Puncture biopsy of bifurcation lymph nodes through bronchoscope. 2Forceps biopsy. 3- Brush biopsy. 4- Puncture biopsy. 5-Transthoracic needle
biopsy of the lung. 6- Thoracoscopic forceps biopsy of the lung. 7 – Open lung
biopsy.
Direct (forceps) biopsy is done by forceps at the affected site in large bore bronchi. It is
performed for verification of diagnosis.
Catheter biopsy helps diagnosis of peripheral bronchial and pulmonary lesions. It is
performed either under local or general anesthesia. Radio opaque heart catheters and metal guides
help direction of catheter into bronchi of respective I, II, IV segments and III-V, VII-X segments.
Manipulation is done in X-ray room. Lesion is reached and traumatized by to and fro movement
of the tip of catheter. Catheter is connected to the trap and electric aspirator.
Brush biopsy is variation of catheter biopsy. Heart catheter contains guide with brush on
the tip. Brush is pushed by 1-2 cm when catheter passes over lesion and then reintroduced into the
catheter. Material from the brush is then examined under microscope.
Transbronchial intrapulmonary biopsy helps receiving pulmonary tissue through bronchi.
This method is used for diagnostics of sarcoidosis, disseminated lesions of lungs in rheumatic
diseases, tumors, and suspicion of metastasizing cancer. Physician introduces fibrobronchoscope
up to affected site, open forceps braches at inspiration (which damages bronchioles), pushes
forceps a little farther and closes forceps at exhalation. One bronchoscopy allows 2-3 biopsies
later examined under microscope.
Transbronchial puncture intrapulmonary biopsy of intrathoracic lymph nodes is used for
differential diagnosis of tuberculosis, sarcoidosis, tumors, lymph node adenopathies.
Sponge biopsy is indicated when lesion is localized in bronchi. Bronchoscopy forceps
hold sterile sponge (0.5x0.5x0.5cm) of porolone. During bronchoscopy sponge is held in contact
with affected mucosa for 30-50 seconds. Sponge then is cut for microscopic examination.
Pleural puncture is performed for diagnostics of pleuritis and for aspiration of exudate in
suppurative pleuritis or hemothorax followed sometimes by lavage of pleural cavity. Spontaneous
pneumothorax requires puncture and aspiration of air; therapeutic pneumothorax requires
puncture and introduction of air. Pleural puncture is necessary for injection of antibiotics or
methylene blue to diagnose bronchial fistula.
Pleural puncture is performed in sitting position. Local anesthesia of skin and intercostal
muscle is done by 0.5% novocaine through fine gauge needle at IV-VII intercostal space between
medial axillar and scapula line. Then large bore needle punctures thoracic wall over upper border
of rib avoiding damage to the vessels and nerve passing under the rib. Needle is directed in
perpendicular fashion to the chest wall; novocaine injection should precede further introduction of
the needle. Pleural puncture is felt by its density followed by drop of resistance. Needle is
connected to the faucet kept closed when syringe is removed to avoid introduction of air into
pleural cavity.
Pulmonary puncture. Transthoracic needle biopsy (TNB) is widely used for diagnosis of
peripheral lesions in lungs or when pleura is affected whenever conventional methods do not
provide enough evidence. It is contraindicated in emphysema, alteration of blood clotting, cor
pulmonale, disease of the single lung, Echinococcus granulosus infestation.
There are two methods of pulmonary TNB, aspiration and puncture biopsy. Former yields
material for cytological examination, former provides enough information also for histology.
TNB is performed under local anesthesia in supine position on the X-ray or computed
tomography table. Lesion is punctured with needle, followed by extraction of the guide and
aspiration of contents with syringe.
Silverman’s needle with guiding troacar allows aspiration followed by puncture biopsy.
Special split needle helps taking biopsy through troacar.
Mediastinoscopy belongs to endoscopic diagnostic operations. It is indicated in alteration
of mediastinal lymph nodes due to unknown cause. Mediastinoscopy is used when previous
bronchoscopy and tracheo-bronchial puncture did not yield enough evidence.
Operation is done under general anesthesia. Skin incision is performed over jugular notch;
trachea is then mobilized by finger down to bifurcation. Mediastinoscope is introduced into this
channel for visualization of paratracheal and mediastinal fat and lymph nodes and their puncture.
Mediastinotomy is diagnostic operation used for the same purposes as mediastinoscopy.
Anterior mediastinum is accessed through resected II or III cartilage rib on either right or left side.
Prescalenic biopsy is diagnostic operation. Enlarged lymph nodes along with fat to the
front of scalene muscle are resected under local anesthesia.
Open lung biopsy is biopsy of lung through thoracotomy under general anesthesia. It is
indicated in disseminated pulmonary lesions of unclear etiology. Strong side of method is yielding
of large bioptates.
Pleuroscopy is indicated for visual inspection of pleural cavity, lungs and for biopsy. It
requires artificial pneumothorax 1-2 days earlier. This method is rarely used.
Study questions.
1. What functional methods are used for diagnostics in patients with tuberculosis?
2. What is purpose of spirometry? What are parameters of external breathing?
3. What types and degrees of ventilation failure do you know?
4. What are chief parameters of ventilation?
5. What causes restrictive and obstructive ventilation failure?
6. What instrumental aided methods of diagnostics of patient with pulmonary
tuberculosis do you know?
7. What is purpose of bronchoscopy?
8. What methods of diagnostics can be used in bronchoscopy?
9. What is purpose of biopsy?
10. What is purpose of pleural puncture?