Dr. Aswini Kumar MohapatraDr. Aswini Kumar Mohapatra

Professor and HeadProfessor and Head

Dept. of Pulmonary MedicineDept. of Pulmonary Medicine

TUBERCULOSISTUBERCULOSIS

PATHOLOGYPATHOLOGY

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PATHOGENESISPATHOGENESIS

PATHOLOGY & PATHOGENESISPATHOLOGY & PATHOGENESIS

Lung- predominant primary siteLung- predominant primary site

Mycobacterium tuberculosisMycobacterium tuberculosisMycobacterium bovisMycobacterium bovis (rare occurrence (rare occurrence

because of pasteurization of milk)because of pasteurization of milk)NTMNTM - - Non Tuberculous Mycobacteria- Non Tuberculous Mycobacteria-

immunodeficient populationimmunodeficient population

Mycobacterium tuberculosisMycobacterium tuberculosis-- non motilenon motile

aerobic aerobic

catalase producingcatalase producing

acid fast bacillus acid fast bacillus (AFB)(AFB)

Tuberculosis is transmitted by aerosolTuberculosis is transmitted by aerosol. . PTB is the predominant form of diseasePTB is the predominant form of disease

Extra pulmonary TB is commonly Extra pulmonary TB is commonly accompanied by pulmonary diseaseaccompanied by pulmonary disease

PATHOLOGYPATHOLOGY

PTB -PTB - Primary TB Primary TB

Post- primary TBPost- primary TB

Primary TBPrimary TB--Infection occurring for the first timeInfection occurring for the first time

Most characteristic feature- Most characteristic feature-

GHON’S COMPLEX GHON’S COMPLEX

(PRIMARY COMPLEX)(PRIMARY COMPLEX)

GHON’S COMPLEXGHON’S COMPLEX--

1. Pulmonary focus 1. Pulmonary focus (Ghon’s focus)(Ghon’s focus)

a sub pleural focusa sub pleural focus

usually < 1cm in dia.usually < 1cm in dia.

can occur anywhere in the lungcan occur anywhere in the lung

2. Draining lymphatics2. Draining lymphatics

3. Hilar nodes3. Hilar nodes

Lesions present in the primary focus as Lesions present in the primary focus as well as lymphnodes -well as lymphnodes - TuberclesTubercles

TUBERCLETUBERCLE--

1.Epitheloid cells1.Epitheloid cells

2.langhan’s giant cells2.langhan’s giant cells

3.Lymphocytes3.Lymphocytes

Centre of the tubercle may undergo necrosis- Centre of the tubercle may undergo necrosis- caseation necrosiscaseation necrosis

Fate of primary complexFate of primary complex--Most heal with or without calcificationMost heal with or without calcificationBacilli escape from the draining nodes to Bacilli escape from the draining nodes to the circulation and then to other parts of the circulation and then to other parts of lung and other organslung and other organsMay fail to heal May fail to heal → → progressive primary progressive primary TBTBEnlarged lymhnodes may compress Enlarged lymhnodes may compress airways airways → → collapse of lobes / segmentcollapse of lobes / segment

EPITUBERCULOSISEPITUBERCULOSIS

Nodes-may erode the airwaysNodes-may erode the airways →→ discharge caseous material into the discharge caseous material into the airways airways → → acute tuberculous acute tuberculous pneumoniapneumonia

Infection from nodes-Infection from nodes-

pleura (pleurisy)pleura (pleurisy)

pericardium (pericarditis)pericardium (pericarditis)

Infection from sub pleural focusInfection from sub pleural focus → → spread spread to pleura to pleura → → pleural effusionpleural effusion

Post primary TBPost primary TB--

Reactivation of latent tuberculosisReactivation of latent tuberculosis

Site of lesions-Site of lesions-

Posterior segment of upper lobePosterior segment of upper lobe

Superior segment of lower lobeSuperior segment of lower lobe

Most characteristic lesion Most characteristic lesion → → cavitycavityCavity contains large no. of bacilli (up to 10Cavity contains large no. of bacilli (up to 1099 organisms)organisms)

May spread endobronchially to other parts of May spread endobronchially to other parts of the lungthe lung

Invasion of the vessel on the wall of the Invasion of the vessel on the wall of the cavity cavity → → haemoptysishaemoptysis

Rupture of the cavity into the pleural spaceRupture of the cavity into the pleural space

TB empyemaTB empyema

pneumothoraxpneumothorax

Prolonged and repeated exposure is Prolonged and repeated exposure is essential for a full blown disease processessential for a full blown disease process

Smear positive PTB Smear positive PTB →→ “OPEN CASE”“OPEN CASE” →→ readily transmit infectionreadily transmit infection

PATHOGENETIC STAGESPATHOGENETIC STAGES--

4 stages4 stages

Stage-I Stage-I stage of onset / stage of no stage of onset / stage of no bacillary growthbacillary growth

Stage-IIStage-II stage of symbiosis stage of symbiosis

Stage-IIIStage-III stage of immunological control stage of immunological control

Stage-IVStage-IV stage of liquefaction stage of liquefaction

CLINICAL FEATURESCLINICAL FEATURES

SymptomsSymptoms--disease of protean manifestations and mimic disease of protean manifestations and mimic many diseases.many diseases.Constitutional & Respiratory symptoms.Constitutional & Respiratory symptoms.ConstitutionalConstitutional--Tiredness, headache, weight loss, fever, night Tiredness, headache, weight loss, fever, night sweats and loss of appetitesweats and loss of appetite Fever- late afternoon or eveningFever- late afternoon or evening Associated laryngeal TB- hoarseness of Associated laryngeal TB- hoarseness of

voice voice AmenorrhoeaAmenorrhoea

RespiratoryRespiratory--

CoughCough- -

most common most common → → min. 3 weeks duration, min. 3 weeks duration, dry or productive dry or productive

Sputum may be mucoid, mucopurulent, purulent or Sputum may be mucoid, mucopurulent, purulent or blood tingedblood tinged

Haemoptysis-Haemoptysis-

blood stain sputum, massive haemoptysis (rupture of blood stain sputum, massive haemoptysis (rupture of bronchial artery)bronchial artery)

Chest pain-Chest pain-

dull aching dull aching acute chest pain- TB pleurisyacute chest pain- TB pleurisy pneumothoraxpneumothorax

Breathlessness-Breathlessness-

extensive tuberculosisextensive tuberculosis

bronchial obstructionbronchial obstruction

pneumothoraxpneumothorax

pleural effusionpleural effusion

Localized wheeze-Localized wheeze-

endobronchial TBendobronchial TB

( pressure of enlarged lymph ( pressure of enlarged lymph nodes on the bronchus ) nodes on the bronchus )

Signs-Signs-Anaemia, cachexiaAnaemia, cachexiaTachycardia- proportionate to feverTachycardia- proportionate to feverClubbing - advanced cases with superadded Clubbing - advanced cases with superadded suppurationsuppuration

Respiratory system examination-Respiratory system examination-Asymmetry of chest wall –retraction, fibrosis or Asymmetry of chest wall –retraction, fibrosis or collapsecollapseTrail’s signTrail’s signHigh-pitched bronchial breathing (tubular) High-pitched bronchial breathing (tubular) →→ TB TB pneumoniapneumoniaLow pitched bronchial breathing (cavernous) Low pitched bronchial breathing (cavernous) →→ cavity, open pneumothoraxcavity, open pneumothorax

Fine crepitations Fine crepitations →→ post-tussive post-tussive crepitationcrepitation → → sign of tuberculosis sign of tuberculosis infiltrationinfiltration

Post-tussive suctionPost-tussive suction →→ over a cavity over a cavity after coughing when its walls are not too after coughing when its walls are not too rigidrigid→→ occurs due to re-entry of air occurs due to re-entry of air

DIAGNOSISDIAGNOSIS1.Laboratory1.Laboratory2.Roentgenography(chest x-ray)2.Roentgenography(chest x-ray)Laboratory- Laboratory- sputumsputum-- Gold standard in the diagnosisGold standard in the diagnosis Detection of AFB in stained smear to be examined Detection of AFB in stained smear to be examined

microscopically microscopically 3 sputum samples to be examined 3 sputum samples to be examined (SPOT-(SPOT-

MORNING- SPOT)MORNING- SPOT) Method Method →→ Z-N staining (Ziehl- Neelson carbol Z-N staining (Ziehl- Neelson carbol

fuchsin stain)fuchsin stain) Sample should contain 10,000 AFB/ml for the AFB Sample should contain 10,000 AFB/ml for the AFB

to be detected by smear examinationto be detected by smear examination

Slide reportingSlide reporting--

No. of bacilli /smearNo. of bacilli /smear resultresult

No AFB/100 oil immersion field 0No AFB/100 oil immersion field 0

1-9 AFB/100 oil immersion field scanty1-9 AFB/100 oil immersion field scanty

10-99AFB/100oil immersion field + (1+)10-99AFB/100oil immersion field + (1+)

1-10 AFB/oil immersion field ++ (2+)1-10 AFB/oil immersion field ++ (2+)

>10 AFB/oil immersion field +++ (3+)>10 AFB/oil immersion field +++ (3+)

Gastric lavageGastric lavage diagnosis of PTB in young children instead of diagnosis of PTB in young children instead of

sputumsputum lavage reveal organism in 30to40% of the cases lavage reveal organism in 30to40% of the cases performed early in the morning performed early in the morning →→ concentration is concentration is

highesthighest Nasogastric tube- stomach contents are aspiratedNasogastric tube- stomach contents are aspirated Fibreoptic bronchoscopyFibreoptic bronchoscopy Bronchoscopic aspirate, bronchial washing, Bronchoscopic aspirate, bronchial washing,

bronchoalveolar lavage(BAL)fluid, Trans bronchial bronchoalveolar lavage(BAL)fluid, Trans bronchial lung biopsylung biopsy

UrineUrineCSFCSFTissueTissuebiopsy specimens of lymph node, liverbiopsy specimens of lymph node, liver

Culture methodsCulture methods--Yield from culture is on average twice as that of Yield from culture is on average twice as that of

microscopymicroscopyTwo types of media commonly usedTwo types of media commonly used 1.egg based 1.egg based →→ L-J media, Pentragnani media, L-J media, Pentragnani media,

ATS media ATS media 2.agar based 2.agar based →→ Middle brook 7H10,7H11 media Middle brook 7H10,7H11 mediaAdvantage-Advantage- (a) more sensitive and can be positive when the (a) more sensitive and can be positive when the

bacterial load in the sample is about 10AFB / mlbacterial load in the sample is about 10AFB / ml (b) for precise identification of the causative (b) for precise identification of the causative

organismorganismDisadvantage- Disadvantage- result is delayed, min.6 wks., whereas in smear it result is delayed, min.6 wks., whereas in smear it

is easy to perform and is cheapis easy to perform and is cheap

Chest radiographyChest radiography--

No chest x-ray pattern is absolutely typical of PTBNo chest x-ray pattern is absolutely typical of PTB

Classical pattern Classical pattern atypical patternatypical pattern

(common in HIV)(common in HIV)

Upper lobe infiltrate interstitial Upper lobe infiltrate interstitial infiltrates infiltrates

(lower zone)(lower zone)

B/L infiltratesB/L infiltrates

Cavitation no cavitationCavitation no cavitation

In vast majority of pts.(>90%)with cavitary PTB In vast majority of pts.(>90%)with cavitary PTB sputum smear is positivesputum smear is positive

PTB with cavitary lesions- repeated negative PTB with cavitary lesions- repeated negative sputum smears – diagnosis to be changedsputum smears – diagnosis to be changed

D/D of CXR finding associated with PTB-D/D of CXR finding associated with PTB-1.Cavitation-1.Cavitation- Infection- pneumoniaInfection- pneumonia lung abscesslung abscess fungal infectionfungal infection Non-infectious- bronchogenic carcinomaNon-infectious- bronchogenic carcinoma connective tissue diseaseconnective tissue disease occupational lung diseaseoccupational lung disease2.Unilateral infiltration-2.Unilateral infiltration- pneumonia pneumonia bronchogenic cabronchogenic ca3.Bilateral infiltration-3.Bilateral infiltration- pneumonia pneumonia connective tissue diseaseconnective tissue disease sarcoidosissarcoidosis4.Mediastinal lymphadenopathy-4.Mediastinal lymphadenopathy- lymphomalymphoma bronchogenic cabronchogenic ca sarcoidosissarcoidosis

Diagnosis of extra pulmonary TBDiagnosis of extra pulmonary TB--

Mainly by HPE (histopathology examination)Mainly by HPE (histopathology examination)

TB lymphadenitis- TB lymphadenitis- presence of caseation presence of caseation

TB meningitis-TB meningitis- CSF examinationCSF examination

CSF pressure highCSF pressure high

clear & cloudyclear & cloudy

increase in WBC count with increase in WBC count with lymphocyte predominant lymphocyte predominant

CSF protein, CSF protein, ↓↓ glucose glucose

Tuberculin skin testTuberculin skin test--Tuberculin-purified protein derived from tubercle Tuberculin-purified protein derived from tubercle bacillibacilli

Purified protein derivative (PPD)Purified protein derivative (PPD)

Injected intradermallyInjected intradermally

Induration read after 48 hrs.Induration read after 48 hrs.

Hypersensitivity reactionHypersensitivity reaction

Positive Tuberculin test- indicates infectionPositive Tuberculin test- indicates infection

Positive tuberculin test- induration > 10mmPositive tuberculin test- induration > 10mm

Negative tuberculin test- induration < 10mmNegative tuberculin test- induration < 10mm

A positive tuberculin test is only one piece A positive tuberculin test is only one piece evidence in favour of dignosis of Tuberculosisevidence in favour of dignosis of Tuberculosis