This document discusses the pathology and pathogenesis of tuberculosis. It begins by identifying the common causative agents of tuberculosis as Mycobacterium tuberculosis and Mycobacterium bovis. It then describes the typical progression of primary tuberculosis, from initial infection of the lung to potential spread to lymph nodes and other organs. Post-primary tuberculosis results from reactivation of latent infection and typically causes lesions in the upper lobes of the lung that can form cavities. The document outlines methods for diagnosing tuberculosis, including sputum smear microscopy, culture, chest radiography, and tests for extra-pulmonary disease.

1. Dr. Aswini Kumar MohapatraDr. Aswini Kumar Mohapatra
Professor and HeadProfessor and Head
Dept. of Pulmonary MedicineDept. of Pulmonary Medicine

2. TUBERCULOSISTUBERCULOSIS
PATHOLOGYPATHOLOGY
&&
PATHOGENESISPATHOGENESIS

3. PATHOLOGY & PATHOGENESISPATHOLOGY & PATHOGENESIS
Lung- predominant primary siteLung- predominant primary site
 Mycobacterium tuberculosisMycobacterium tuberculosis
 Mycobacterium 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

4. Mycobacterium tuberculosisMycobacterium tuberculosis--
non motilenon motile
aerobicaerobic
catalase producingcatalase producing
acid fast bacillusacid 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 commonlyExtra pulmonary TB is commonly
accompanied by pulmonary diseaseaccompanied by pulmonary disease

5. PATHOLOGYPATHOLOGY
PTB -PTB - Primary TBPrimary 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 COMPLEXGHON’S COMPLEX
(PRIMARY COMPLEX)(PRIMARY COMPLEX)

6. GHON’S COMPLEXGHON’S COMPLEX--
1. Pulmonary focus1. 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 asLesions present in the primary focus as
well as lymphnodes -well as lymphnodes - TuberclesTubercles

7. 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

8. Fate of primary complexFate of primary complex--
Most heal with or without calcificationMost heal with or without calcification
Bacilli escape from the draining nodes toBacilli escape from the draining nodes to
the circulation and then to other parts ofthe circulation and then to other parts of
lung and other organslung and other organs
May fail to healMay fail to heal →→ progressive primaryprogressive primary
TBTB
Enlarged lymhnodes may compressEnlarged lymhnodes may compress
airwaysairways →→ collapse of lobes / segmentcollapse of lobes / segment
EPITUBERCULOSISEPITUBERCULOSIS

9. Nodes-may erode the airwaysNodes-may erode the airways →→
discharge caseous material into thedischarge caseous material into the
airwaysairways →→ acute tuberculousacute 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 →→ spreadspread
to pleurato pleura →→ pleural effusionpleural effusion

10. 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

11. Most characteristic lesionMost characteristic lesion →→ cavitycavity
Cavity contains large no. of bacilli (up to 10Cavity contains large no. of bacilli (up to 1099
organisms)organisms)
May spread endobronchially to other parts ofMay spread endobronchially to other parts of
the lungthe lung
Invasion of the vessel on the wall of theInvasion of the vessel on the wall of the
cavitycavity →→ haemoptysishaemoptysis

12. Rupture of the cavity into the pleural spaceRupture of the cavity into the pleural space
TB empyemaTB empyema
pneumothoraxpneumothorax
Prolonged and repeated exposure isProlonged and repeated exposure is
essential for a full blown disease processessential for a full blown disease process
Smear positive PTBSmear positive PTB →→ “OPEN CASE”“OPEN CASE” →→
readily transmit infectionreadily transmit infection

13. PATHOGENETIC STAGESPATHOGENETIC STAGES--
4 stages4 stages
Stage-IStage-I stage of onset / stage of nostage of onset / stage of no
bacillary growthbacillary growth
Stage-IIStage-II stage of symbiosisstage of symbiosis
Stage-IIIStage-III stage of immunological controlstage of immunological control
Stage-IVStage-IV stage of liquefactionstage of liquefaction

14. CLINICAL FEATURESCLINICAL FEATURES
SymptomsSymptoms--
disease of protean manifestations and mimicdisease of protean manifestations and mimic
many diseases.many diseases.
Constitutional & Respiratory symptoms.Constitutional & Respiratory symptoms.
ConstitutionalConstitutional--
Tiredness, headache, weight loss, fever, nightTiredness, 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 ofAssociated laryngeal TB- hoarseness of
voicevoice
 AmenorrhoeaAmenorrhoea

15. RespiratoryRespiratory--
CoughCough--
most commonmost common →→ min. 3 weeks duration,min. 3 weeks duration,
dry or productivedry or productive
Sputum may be mucoid, mucopurulent, purulent orSputum may be mucoid, mucopurulent, purulent or
blood tingedblood tinged
Haemoptysis-Haemoptysis-
blood stain sputum, massive haemoptysis (rupture ofblood stain sputum, massive haemoptysis (rupture of
bronchial artery)bronchial artery)
Chest pain-Chest pain-
dull achingdull aching
acute chest pain- TB pleurisyacute chest pain- TB pleurisy
pneumothoraxpneumothorax

16. 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 )

17. Signs-Signs-
Anaemia, cachexiaAnaemia, cachexia
Tachycardia- proportionate to feverTachycardia- proportionate to fever
Clubbing - advanced cases with superaddedClubbing - advanced cases with superadded
suppurationsuppuration
Respiratory system examination-Respiratory system examination-
Asymmetry of chest wall –retraction, fibrosis orAsymmetry of chest wall –retraction, fibrosis or
collapsecollapse
Trail’s signTrail’s sign
High-pitched bronchial breathing (tubular)High-pitched bronchial breathing (tubular) →→ TBTB
pneumoniapneumonia
Low pitched bronchial breathing (cavernous)Low pitched bronchial breathing (cavernous) →→
cavity, open pneumothoraxcavity, open pneumothorax

18. Fine crepitationsFine crepitations →→ post-tussivepost-tussive
crepitationcrepitation →→ sign of tuberculosissign of tuberculosis
infiltrationinfiltration
Post-tussive suctionPost-tussive suction →→ over a cavityover a cavity
after coughing when its walls are not tooafter coughing when its walls are not too
rigidrigid→→ occurs due to re-entry of airoccurs due to re-entry of air

19. DIAGNOSISDIAGNOSIS
1.Laboratory1.Laboratory
2.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 examinedDetection of AFB in stained smear to be examined
microscopicallymicroscopically
 3 sputum samples to be examined3 sputum samples to be examined (SPOT-(SPOT-
MORNING- SPOT)MORNING- SPOT)
 MethodMethod →→ Z-N staining (Ziehl- Neelson carbolZ-N staining (Ziehl- Neelson carbol
fuchsin stain)fuchsin stain)
 Sample should contain 10,000 AFB/ml for the AFBSample should contain 10,000 AFB/ml for the AFB
to be detected by smear examinationto be detected by smear examination

20. 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+)

21. Gastric lavageGastric lavage
 diagnosis of PTB in young children instead ofdiagnosis of PTB in young children instead of
sputumsputum
 lavage reveal organism in 30to40% of the caseslavage reveal organism in 30to40% of the cases
 performed early in the morningperformed early in the morning →→ concentration isconcentration 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 bronchialbronchoalveolar lavage(BAL)fluid, Trans bronchial
lung biopsylung biopsy
UrineUrine
CSFCSF
TissueTissue
biopsy specimens of lymph node, liverbiopsy specimens of lymph node, liver

22. Culture methodsCulture methods--
Yield from culture is on average twice as that ofYield from culture is on average twice as that of
microscopymicroscopy
Two types of media commonly usedTwo types of media commonly used
1.egg based1.egg based →→ L-J media, Pentragnani media,L-J media, Pentragnani media,
ATS mediaATS media
2.agar based2.agar based →→ Middle brook 7H10,7H11 mediaMiddle brook 7H10,7H11 media
Advantage-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
organismorganism
Disadvantage-Disadvantage-
result is delayed, min.6 wks., whereas in smear itresult is delayed, min.6 wks., whereas in smear it
is easy to perform and is cheapis easy to perform and is cheap

23. Chest radiographyChest radiography--
No chest x-ray pattern is absolutely typical of PTBNo chest x-ray pattern is absolutely typical of PTB
Classical patternClassical pattern atypical patternatypical pattern
(common in HIV)(common in HIV)
Upper lobe infiltrate interstitialUpper lobe infiltrate interstitial
infiltrates (lower zone)infiltrates (lower zone)
B/L infiltratesB/L infiltrates
Cavitation no cavitationCavitation no cavitation
In vast majority of pts.(>90%)with cavitary PTBIn vast majority of pts.(>90%)with cavitary PTB
sputum smear is positivesputum smear is positive
PTB with cavitary lesions- repeated negativePTB with cavitary lesions- repeated negative
sputum smears – diagnosis to be changedsputum smears – diagnosis to be changed

24. 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 disease
2.Unilateral infiltration-2.Unilateral infiltration- pneumoniapneumonia
bronchogenic cabronchogenic ca
3.Bilateral infiltration-3.Bilateral infiltration- pneumoniapneumonia
connective tissue diseaseconnective tissue disease
sarcoidosissarcoidosis
4.Mediastinal lymphadenopathy-4.Mediastinal lymphadenopathy-
lymphomalymphoma
bronchogenic cabronchogenic ca
sarcoidosissarcoidosis

25. 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 caseationpresence of caseation
TB meningitis-TB meningitis- CSF examinationCSF examination
CSF pressure highCSF pressure high
clear & cloudyclear & cloudy
increase in WBC count withincrease in WBC count with
lymphocyte predominantlymphocyte predominant
CSF protein,CSF protein, ↓↓ glucoseglucose

26. Tuberculin skin testTuberculin skin test--
Tuberculin-purified protein derived from tubercleTuberculin-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 pieceA positive tuberculin test is only one piece
evidence in favour of dignosis of Tuberculosisevidence in favour of dignosis of Tuberculosis