PULMONARY TUBERCULOSIS

Dr. Arun K Mahato

Dept. of Internal Medicine
NoMCTH, Biratnagar
 Some facts about T.B.
• Someone in the world is newly infected with TB
bacilli every second

• One-third of the world's population is currently

infected with the TB bacillus
– 10% of people infected with TB become sick or
infectious at some time during their life
• People with HIV and TB infection are much more likely to develop TB
per 100,000 citizens. Red = >300, orange = 200-300;
yellow = 100-200; green 50-100; blue = <50 and grey = n/a.

.
• Tuberculosis second leading infectious cause
of death worldwide (after AIDS)

• killing around 2 million people per year.

(despite it being a potentially curable disease.)

• should often be considered as a differential

diagnosis in many conditions
 Pathophysiology

Pathophysiology
 Adaptive immune system
antigen-specific and requires the recognition of
specific “non-self” antigens

stem cells in the bone marrow

lymphocytes

B cells -involved in the T cells are involved

humoral immune in cell-mediated
response immune response
Antibody production
T Lymphocyte
 Pulmonary Tuberculosis

• Primary

• Progressive-primary

• Postprimary
 .

• spread by airborne droplets, containing

Mycobacterium tuberculosis (MTB).
• Droplets can remain airborne for hours after
expectoration, because of their small size.
• Infectious droplets inhaled and lodged in the distal
airways.
• taken up by alveolar macrophages
– successful containment of the infection
– progression to primary disease
 successful containment
• MTB replicates in alveolar macrophages, with
spread via the lymphatics to hilar lymph nodes.
❑Development of specific cell-mediated
immunityand & delayed-type hypersensitivity at 2–
10 weeks
• limits further bacterial replication & disease spread.
• Unless there is a deficiency in cell-mediated
immunity, active disease may never occur.
• Some of the bacilli remain dormant and viable for
many years - latent TB infection

• detectable only by means of a

• positive purified protein derivative(PPD)

tuberculin skin test

• radiologically identifiable calcification at the

site of the primary lung infection or in regional
lymph nodes.
 Primary Tuberculosis
• Primary tuberculosis is the most common form of
pulmonary tuberculosis in infants and children.
incidence has increased in adults
Involvements
• Lung parenchyma
• lymphadenopathy
• pleural effusion – more common in post primary
• miliary disease
• lobar or segmental atelectasis
• Hypersensitivity - Erythema nodosum, Phlyctenular
conjunctivitis.
 Parenchymal disease
• Ghon focus
• small area of granulomatous inflammation,
only detectable by chest X-ray if it calcifies
• developes in the lung of a previously
uninfected individual
• affects the areas of greatest ventilation
– right middle lobe
– lower lobes
– anterior segment of the upper lobes.
• segmental or lobar airspace consolidation-
homogeneous, with ill-defined margins
• Caseous necrosis occurs centrally within the lung
parenchymal opacity, decreasing its size.

Langhan’s giant cell

• Cavitation in Ghon focus does not occur.
• As the host immune response continues, healing
begins.
• lung opacity become rounded with healing,
• continues to shrink until only a small nodule
remains.
• nodule may become calcified or ossified, resulting
in a calcified granuloma.
• organisms may remain quiescent within this nodule,
serving as a possible source for reactivation of
disease.
 Lymphadenopathy
• bacilli within macrophages drain out from the area through
the lymph vessels – Lymphangitis & affect the Lymph
nodes.
• presence of hilar and mediastinal lymphadenopathy
lymphadenopathy conspicuously absent in post primary
tuberculosis.
• Lymphadenopathy without a parenchymal opacity may
occur as the only manifestation of primary pulmonary
tuberculosis – commonly seen with HIV infection.
• Lymphadenopathy most common in the ipsilateral hilar
region. Hilar lymphadenopathy seen in approx 60% of
children with primary tuberculosis
• paratracheal adenopathy and subcarinal lymphadeno pathy
also seen
 lobar or segmental atelectasis
• Airway compression by adjacent lymphadenopathy
with resultant atelectasis. Right middle lobe
syndrome - compression of the right middle lobe
bronchus by hilar lymph nodes leads to lobar
collapse
• Mucosal infection with resultant ulceration and
long-term stricture formation
• Broncholithiasis, ie, extrinsic erosion of a bronchus
by adjacent lymphadenopathy with extrusion of
calcified material into the bronchus
• Endobronchial spread of infection
Ghon's or Primary complex is combination of

– 1. Ghon's focus (area of initial parenchymal

infection by airborne bacillus)

– 2. Lymphangitis

– 3. Lymphadenits
 Clinical Features
• Primary tuberculosis usually a self-limited infection
seen in children in endemic regions.
• 60% of children and 5% of adults with primary
tuberculosis are asymptomatic.
• may be minimally symptomatic with minimal
constitutional symptoms
• Fever
• malaise
• weight loss
• Cough
• occasional hemoptysis.
• Physical findings are minimal in most of cases

• In some there can be features of

• Consolidation
• Pleural effussion
• Atelectsis
 Progressive primary tuberculosis
• occurs in the setting of acute infection in
patients with minimal or marked immune
compromise.
• Patients with progressive primary tuberculosis
become acutely ill
• May have extensive lung parenchymal
opacities and cavitation.
• Hypoxia and death may occur.
 progression to primary disease
• Active disease when the host's immune response unable to
contain MTB replication
• occurring most often in the lung parenchyma and hilar
lymph nodes.
• can occur in any organ, from haematogenous spread.
• Factors responsible
– Age - most common in young children
– host immunity – immuno suppressed adults
– time since infection.
• estimated lifetime risk of clinical disease of a child newly
infected with MTB is about 10%
 Diagnosis
• based on a combination of
– tuberculin skin testing (purified protein derivative
testing or mantoux test )
– sputum cultures
– Radiography
• Bronchoscopy may be required to obtain
specimens.
 Tuberculin skin test
Mantoux test
Heaf test
Tyne test
• Tuberculin is a glycerine extract of the tubercule
bacilli - Purified protein derivative (PPD) tuberculin

• A standard dose of 10 Tuberculin units (0.1 ml)

injected intradermally

• read 48 to 72 hours later. A person exposed to the

bacteria mounts an immune response
(hypersensitivity or allergy not immunity) in the skin
containing the bacterial proteins.
• reaction is read by measuring the diameter of
induration (palpable raised hardened area) across
the forearm in millimeters after 48-72 hrs.
Erythema (redness) should not be measured.
 Classification of tuberculin reaction

5 mm or more is positive in

• HIV-positive person
• Recent contacts of TB case
• Persons with nodular or fibrotic changes on chest x-
ray consistent with old healed TB
• Patients with organ transplants and other immuno
suppressed patients
 10 mm or more is positive in
• Injection drug users
• Residents and employees of high-risk congregate
settings (e.g., prisons, nursing homes, hospitals,
homeless shelters, etc.)
• Mycobacteriology lab personnel
• Persons with clinical conditions that place them at
high risk (diabetes, prolonged corticosteroid
therapy, leukemia, end-stage renal disease, chr.
malabsorption syndromes, low body weight, etc)
• Children less than 4 years of age, or children and
adolescents exposed to adults in high-risk
categories
 15 mm or more is positive in

– Persons with no known risk factors for TB

• A tuberculin test conversion is defined as an

increase of 10 mm or more within a 2-year period,
regardless of age.
• False positive
• previous administration of BCG vaccine
• Infection with nontuberculous mycobacteria
• False negative
• HIV(if CD4 count < 200 cells/ml)
• severe TB disease
• Renal failure
• diabetes
• immunosuppressive drugs
• sarcoidosis
• Extremes of age -old age or newborn infants
• improper storage, insufficient dose
• inadvertent subcutaneous injection.
 Postprimary Tuberculosis
• reactivation of a latent primary infection

or less commonly from

• repeat infection of a previously sensitized host

 Medical factors responsible for reactivation
• Diabetes
• renal disease
• malignant disease
• systemic chemotherapy
• steroids
• Smoking
• Gastrectomy
• H.I.V.
• Pneumoconiosis
• Pulmonary reactivation usually occurs in
– apical and posterior segments of the upper lobes
– superior segments of the lower lobes
Due to
• higher oxygen tension
• reduced perfusion and lymphatic clearance
 Pathogenesis
• in primary TB development of immunity
arrests the spread of disease
 .

• Unchecked proliferation of the mycobacteria results

in rapid necrosis because of preexisting
hypersensitivity.
(Mycobacteria as such do not produce any toxin and does not cause tissue necrosis
by it self.)

• disease is usually progressive in contrast to that of

primary TB ( caseation & fibrosis goes on together in lung parenchyma)

• in primary TB development of immunity arrests the

spread of disease
 Patterns of involvement
• Erosion into adjacent anatomic structures results in
further spread. The classic postprimary TB
progression involves
• cavitation into a bronchus with endobronchial
spread – most common
• Other patterns can cause erosion into the
• blood vessels
• pleural space
• lymphatics.
 Symptoms
• Productive cough
• Haemoptysis
• Breathlessness
• Systemic symptoms
– weight loss
– Evening rise of temperature & night sweat
– malaise
• Chest pain.
 Haemoptysis
• more common with cavitatory disease
• 2/3rds smear positive.
• Mostly small volume.
• Massive haemoptysis rare
– Erosion of a blood vessel
– as a consequence of destruction of a lobe, with
consequent bronchiectasis formation (secondary
aspergillus infection or mycetoma in a healed TB cavity).

• Most haemoptysis resolve with anti tuberculous

chemotherapy.
 Signs
• are often non-specific.
• Examination may be normal
• Crackles or crepitations - at the apices, post tussive
• Signs of a pleural effusion
• Signs of consolidation (with extensive disease)
• Signs of fibrosis
• Signs of weight loss/underlying immuno
compromise
• Look for evidence of extrapulmonary disease, e.g.
skin, joints, CNS, retina, and spinal disease.
 Cavitation
• a distinguishing feature of postprimary TB
• Typical cavities thick walled and irregular.
• Air-fluid levels uncommon and usually indicate
superinfection.
• Cavitation of infection into the bronchial tree
results in 'open' TB – sputum positive. lead to
– endobronchial spread to the remaining lung
• Cavitation can
– rupture into the pleural space causing empyema
– bronchopleural fistula - Pneumothorax
• persistence of cavitation without healing is unusual and
should be investigated to exclude fungal infection in
patients with persist. hemoptysis.
Investigations
Routine investigations
• Circumstantial (ESR, CRP, anaemia etc.)
• Blood tests
– Baseline FBC,
– renal, and liver function tests

Useful to document normal baseline levels before

starting antituberculous chemotherapy

• Consider HIV test

• Sputum examination
• Culture
• Radiology
• X ray
• C.T. scan
• Bronchoscopy
• Biopsy from extrapulmonary sites, e.g. neck
lymph nodes
• Tuberculin skin test
• polymerase chain reaction (PCR)
 Sputum examination
• Ziehl Neelson (ZN) stain
• ZN only 50 - 80% sensitive
• Smear negative disease accounts for 20% of disease
transmission; smear positive cases are more
infectious
• Induced sputum is as effective as BAL if the CXR
shows changes consistent with active disease
• Gastric washings specially in children who swallow
the sputum
• induced with nebulised hypertonic saline if not
expectorating
 Culture
• required for definitive diagnosis
• vital for drug resistance testing
• Sputum cultured on Lowenstein-Jensen
medium for 4-8 weeks
• Liquid culture (Bactec or Becton-Dickinson) has the
advantage of shorter culture times.
• Sensitivity determination takes another 3-4
weeks
 Bronchoscopy
• needed to obtain BAL samples if there is a high
index of clinical suspicion with non-productive
cough, or unhelpful sputum culture.
• In extensive disease, macroscopic broncho scopic
abnormalities directly visualized
• erythematous or ulcerated airways
• Granulation tissue
• enlarged lymph nodes.
• Nodes can perforate or protrude into the
bronchial lumen, extruding caseous material
into the airway.
• Biopsy from extrapulmonary sites, e.g. neck
lymph nodes

• Tuberculin skin test - useful if grade 3 or 4

(suggesting active disease) or if negative
 Radiology
• manifests as cavitary lesions.
• Upper-lobe involvement with cavitation and the
absence of lymphadenopathy
• usually involved pulmonary segments
– apical or posterior segments of the upper lobe
– superior segment of a lower lobe
• Cavitation - feature of postprimary TB
• seen in about half of cases & seen on CT scans
• Typical cavities thick walled and irregular.
• Air-fluid levels uncommon-indicate superinfection
 radiological features mimicking T.B.
• pyogenic infections
• sarcoidosis
• vasculitis
• parasitic infections
• bronchiolitis obliterans and organizing
pneumonia (BOOP)
• malignancies.
 Chest X-Ray Findings that Can Suggest
ACTIVE TB
• Infiltrate
• Any cavitary lesion
• Nodule with poorly defined margins
• Pleural effusion
• Hilar or mediastinal lymphadenopathy
• miliary TB nodules of millet size (1 to 2
millimeters) distributed throughout the
parenchyma.
 Chest X-Ray Findings that Can Suggest
INACTIVE TB
• Discrete fibrotic scar or linear opacity Calcification can be
present within - “fibrocalcific” scar.
• Discrete nodule(s) without calcification—One or more
nodular densities with distinct borders and without any
surrounding airspace opacification.
• Discrete fibrotic scar with volume loss
• Discrete nodule(s) with volume loss or retraction nodular
densities with distinct borders and no surrounding airspace
opacification with reduction in the space occupied by the
upper lobe.
• polymerase chain reaction (PCR) for T.B.
detect mycobacterial D N A

• antibody assays to detect the release of

interferon gamma in response to
mycobacteria
 CT scan
• more sensitive than CXR, especially for
smaller areas of disease.
• shows cavitatory disease, and
• signs of airway disease - the tree in bud
appearance, useful for differentiating
between active disease, and non-active, old
disease.
Drug treatment
WHO in 1993 declared TB as a global
emergency.

➢ TB bacilli is a slow growing organism.

➢ Disease is usually chronic.

➢ Therapeutic problems-
➢ 1)patient compliance.
➢ 2)drug toxicity.
➢ 3)Development of resistance
➢ To cure patients.

➢ To prevent death.

➢ To prevent relapse.

➢ To decrease transmission of TB.

➢ To eradicate the disease at a

point of time.
There are three main properties-
➢ BACTERICIDAL ACTIVITY-
INH, rifampin, pyrazinamide,
streptomycin.
➢ STERILIZING ACTIVITY-
rifampin, pyrazinamide.
➢ ABILITY TO PREVENT RESISTANCE-
streptomycin, ethambutol, thioacetazone.
➢ SECOND LINE DRUGS
- Quinolones .

- Capreomycin(15mg/kg)
- Rifabutin
- Amikacin(15mg/kg)
- Ethionamide(10-20mg/kg)
- Para-Aminosalicylic Acid(150mg/kg)
- Cycloserine(10-20mg/kg)

➢ NEWER DRUGS
- Rifapentine
➢ Managed as outpatient
➢ Isolation not necessary beyond 2wks-3wks
of treatment. as sputum becomes negative.
➢ Full 6month treatment required to prevent
relapse.
➢ Follow up should be two visits monthly.
➢ Patient must be aware of the side effects in
order to continue with treatment.
➢ ISONIAZID(H): 4-6mg/kg orally, max-
300mg.
pyridoxin:10mg daily with INH.
➢ RIFAMPICIN(R): 8-12mg/kg/day (10mg),
max-600mg/day.
➢ PYRAZINAMIDE(Z): 20-30mg/kg/day
(25mg/kg).
➢ STREPTOMYCIN(S): 12-18mg/kg/day
(15mg/kg) im deep.
➢ ETHAMBUTOL(E):15-20mg/kg/day.
It is necessary to monitor visual acuity and colour
vision of patient.
 Short course chemotherapy (SCC)
• WHO expert group has firm clear cut treatment
guidelines in year 1997 for different categories of TB
patients
• The regimen 6-9 month duration & dose of first line
anti –TB drugs has been standardized on body
weight basis for both adults & children
• Regimens in 2 phases:
Initial intensive phase –kill bacilli
→became sputum negative
Continuation Phase –Eliminate persister or
remaining bacilli
→ Prevent relapse
 Role of corticosteroids

• Indicated in small doses in

• Pericarditis

• Meningitis

• Pleural effusion
 Tuberculosis in pregnant women

WHO consider H R & Z to be safe to

foetus
Recommend standard six month duration
2HRZ + 4 HR
DOTS –Directly observed treatment short course
➢
Since the 1990s the World Health Organization
Directly Observed Therapy Short Course (DOTS)
management strategy has become internationally
recommended approach for tuberculosis (TB)
control programmes.

By the beginning of the new Millennium, 149

countries in the world had adopted the DOTS
strategy to varying degrees and important
measures of DOTS success (case detection and
treatment success) were included in the
Millennium Development Goals framework
 Aim of DOTS
• To ensure drugs are actually consumed
The WHO Directly Observed Treatment Short Course (DOTS)
strategy employing a standardized treatment for 6 months
produces the highest cure rates for drug sensitive TB
WHEN TO START TREATMENT .

3 sputum smears
• .

3 or 2 positive 1 positive 3 negative

Antibiotics
X- ray
Symptoms persist

Sputum +ve TB TB X-ray +ve

Sputum –ve TB

ATT
➢ Treatment should include at 4 drugs which is
never used before by the patient.
➢ Treatment should be given daily and directly
observed.
➢ Initial phase of at least 3-6months.
➢ Followed by continuation phase of 12-
18months.
➢ This is conducted with atleast 3 of the most
active and best tolerated drugs.
➢ The standard treatment regimen are effective in
HIV +ve as well as HIV –ve.
➢ There can be adverse drug reactions sometimes.
➢ Three important thing should be considered-
-increased frequency of paradoxical reactions.
-drug interactions between HAART and rifamycins.
-development of rifampin monoresistance with
widely spread intermittent treatment.
➢ ISONIAZID
- peripheral neuropathy.
- hepatitis.
- rash.
➢ RIFAMPIN
- febrile reactions.
- hepatitis.
- rash.
- GIT disturbances
➢ PYRAZINAMIDE
- hepatitis.
- GIT disturbances.
- hyperuricemia.
➢ STREPTOMYCIN
- 8th nerve damage.
- rash.
➢ ETHAMBUTOL
- retrobulbar neuritis.
- arthalgia
➢ BCG vaccine - Bacillus Calmette-Guérin
prepared from a strain of the attenuated
(weakened) live bovine tuberculosis bacillus,
Mycobacterium bovis that has lost its virulence
in humans by being specially cultured in an
artificial medium for year
➢ Effectivity is controversial
➢ prevents serious forms of TB in children -
disseminating dis including TB Meningitis.
➢ WHO recommend that BCG be given to all
children born in countries highly endemic for TB
because it protects against miliary TB and TB
meningitis
• No protective efficacy of BCG for preventing
pulmonary TB in adolescents and adults
 Other uses
• Leprosy: BCG has a small protective effect against
leprosy
• Cancer immunoterapy – in treatment of
• bladder cancer
• colorectal cancer
• chronic inflammatory bladder problems with
unknown etiology. It is instilled directly into the
bladder
• Not given in HIV persons
 CHRONIC COMPLICATIONS OF PULMONARY TB

PULMONARY

•Massive haemoptysis
•Cor pulmonale
•Fibrosis/emphysema
•Atypical mycobacterial infection
•Aspergilloma
•Lung/pleural calcification
•Obstructive airways disease
•Bronchiectasis
•Bronchopleural fistula
Non-pulmonary

•Empyema necessitans (Chronic undetected empyema)

•Laryngitis
•Enteritis
•Anorectal disease
•Amyloidosis
•Poncet's polyarthritis- Allergic response to tuberculin
“allergic” response to tuberculoprotein
• Bronchiectasis, bronchial obstruction, and airway stenosis
may result from endobronchial disease
• Pleural disease is due either to
– primary progressive disease or
– reactivation of latent infection.
(represents an increased immune response a delayed type
hypersensitivity reaction to mycobacterial antigens)
• Pneumothorax results from rupture of a peripheral cavity.
Can lead to the formation of a bronchopleural fistula
• Draining abscess
• Right middle lobe syndrome compression of the right
middle lobe bronchus by hilar lymph nodes leads to lobar
collapse
•THANK YOU