Tuberculosis

pathology inflammation

1. TUBERCULOSIS

2. Learning Objectives
•Introduction
•Etiology
•Risk Factors
•Transmission
•Sites
•Pathogenesis of Tuberculosis.
•Types of Tuberculosis
•Clinical
•Diagnosis

3. Introduction:
•ItisaChronicGranulomatousinflammatory
infectiousdiseasecausedbyMycobacterium
tuberculosisinhumans.

4. Etiology:
CAUSATIVEORGANISM
•TuberclebacillusorKoch’sbacilluscalled
Mycobacteriumtuberculosiscausestuberculosisin
thelungsandothertissuesofthehumanbody.
•Theorganismisastrictaerobeandthrivesbestin
tissueswithhighoxygentensionsuchasintheapex
ofthelung.
•Outofvariouspathogenicstrainsforhumandisease
includedinMycobacteriumtuberculosiscomplex,
currentlythemostcommonisM.tuberculosis
hominis(humanstrain).

5. •M.tuberculosisbovis(bovinestrain)usedto
becommonpathogentohumanbeingsduring
theeraofconsumptionofunpasteurisedmilk
butpresentlyconstitutesasmallnumberof
humancases
•InfectionwithM.avium-intracellulare(avian
orbirdstrain)iscommoninpatientswith
HIV/AIDS

6. Risk Factors:
•MorecommonindevelopingcountriesofAsia,
AfricaandLatinAmerica.
•Malnutrition.
•Inadequatemedicalcare.
•Poverty.
•Crowding.
•Chronicdebilitatingconditionslikeuncontrolled
diabetes.
•Alcoholismandimmunocompromisedstates.
•Inthewesterncountries,therehasbeena
resurgenceoftuberculosisduetoHIV-AIDS.

7. Mode of Transmission:
•Human beings acquire infection with tubercle bacilli
by one of the following routes:
1.Inhalationoforganismspresentinfreshcough
dropletsorindriedsputumfromanopencaseof
pulmonarytuberculosis.

8. 2.Ingestionoftheorganismsleadsto
developmentoftonsillarorintestinal
tuberculosis.

9. 3.Inoculationoftheorganismsintotheskin
mayrarelyoccurfrominfectedpostmortem
tissue.

10. 4.Transplacentalrouteresultsindevelopment
ofcongenitaltuberculosisinfoetusfrom
infectedmotherandisararemodeof
transmission.

11. Sites:
•PULMONARY REGION –85 %
•EXTRA-PULMONARY SITES-15 %
-Lymph Nodes (most common)
-G.U.T
-Bones & Joints
-Intestine
-Meninges
-Skin

12. Pathogenesis of Tuberculosis:
EVOLUTION OF TUBERCLE
•Thesequenceofeventswhichtakeplacewhen
tuberclebacillientersbody:
TUBERCLE BACILLI ENTRY
If bacilli enters through blood
Neutrophils are evoked initially which
are rapidly destroyed by the organisms.
Later by macrophages and T cells.
If the tubercle bacilli are inhaled into the
lung alveoli
Macrophages predominate the picture
from the beginning.

13. Tubercle Bacilli engulfment by Macrophages
Macrophages try to kill the bacteria or die away themselves.
Macrophages present bacilli to CD4+T lymphocytes
Activated lymphocytes release lymphokines.
IL-1, IL-2, Interferon-γ TNF-α
PROLIFERATION OF
MORE T CELLS
ACTIVATES MACROPHAGES FIBROBLAST PROLIFERATION
If Poorly degradable bacilli are present

14. ACTIVATED MACROPHAGES TRANSFORM TO
EPITHELIOID CELLS AFTER 2 -3 DAYS
SOME MACROPHAGES, UNABLE TO DESTROY TUBERCLE
BACILLI, FUSE TOGETHER AND FORM MULTINUCLEATED
GIANT CELLS.-LANGHAN TYPE
Around the mass or cluster of epithelioid cells and a few giant
cells, a zone of lymphocytes and plasma cells is formed which
is further surrounded by fibroblasts.
The lesion at this stage is called HARD TUBERCLE due to
absence of central necrosis.

15. •Within10-14days,thecentreofthecellularmass
beginstoundergocaseationnecrosis,characterized
bycheesyappearanceandhighlipidcontent.
•ThisstageiscalledSOFTTUBERCLEwhichisthe
hallmarkofTuberculouslesions
Caseation Necrosis

16. ***
•Thesofttuberclewhichisafully-developed
granulomawithcaseouscentredoesnotfavour
rapidproliferationoftuberclebacilli.
•Acid-fastbacilliaredifficulttofindinthese
lesionsandmaybedemonstratedatthe
marginsofrecentnecroticfociandinthewalls
ofthecavities.

17. Fate of Tubercles:
Thefateofagranulomaisvariable:
1.COLDABSCESS:
-Thecaseousmaterialmayundergoliquefactionand
extendintosurroundingsofttissues,dischargingthe
contentsonthesurface.
-Thisiscalledcoldabscessalthoughtherearenopus
cellsinit.

18. 2.SINUSTRACTS:
-Intuberculosisoftissueslikebones,joints,
lymphnodesandepididymis,sinusesare
formedandthesinustractsarelinedby
Tuberculousgranulationtissue.

19. 3.SIZEINCREASE:
-Theadjacentgranulomasmaycoalesce
togetherenlargingthelesionwhichis
surroundedbyprogressivefibrosis.

20. 4.CALCIFICATION&OSSIFICATION:
-Inthegranulomaenclosedbyfibroustissue,
calciumsaltsmaygetdepositedinthecaseous
material(dystrophiccalcification)and
sometimesthelesionmayevengetossified
overtheyears.
dystrophic calcification

21. Types of Tuberculosis:
•Infectionwithtuberclebacilliisof2main
types:
1.PrimaryTuberculosis.
2.SecondaryTuberculosis.

22. 1.Primary Tuberculosis:
•Theinfectionofanindividualwhohasnot
beenpreviouslyinfectedorimmunisedis
calledPrimaryTuberculosisorGhon’s
complexorChildhoodTuberculosis.

23. Sites:
•Themostcommonlyinvolvedtissuesfor
primarycomplexare:
-LungsandHilarlymphnodes.
•Othertissueswhichmayshowprimary
complexare
-TonsilsandCervicallymphnodes
-Smallintestineandmesentericlymphnodes.

24. Primary complex or Ghon’s complex
•PrimarycomplexorGhon’scomplexisthelesion
producedinthetissueofportalofentrywithfociin
thedraininglymphaticvesselsandlymphnodes.

25. Ghon's Complex in Lungs:
•It consists of 3 components:
1.Pulmonary component
-It is 1-2 cm solitary area of primary Tuberculous foci.
-Subpleural focus in the upper part of Lower lobe.
2.Lymphatic vessel component
-Lymphatics draining the lung lesion contain
phagocytes containing bacilli.
3.Lymph node component
-Enlargedhilarandtracheo-bronchiallymphnodesinthe
areadrained.
-Theaffectedlymphnodesaremattedandshowcaseation
necrosis.

27. Fate Of Primary Tuberculosis
•Primarycomplexmayhaveoneofthefollowing
sequelae:
1.Fibrosis,CalcificationandOssification.

28. 2. Progressive primary tuberculosis:
•Caseousmaterialisdisseminatedthrough
bronchitotheotherpartsofthesamelungor
theoppositelung.

29. 3.PrimaryMiliaryTuberculosis:
•Bacillimayenterthecirculationthrough
erosioninabloodvesselandspreadby
haematogenousroutetoothertissuesand
organs.
•Thelesionsmaybeseeninorganslikethe
liver,spleen,kidney,brainandbonemarrow.

30. 3.ProgressiveSecondaryTuberculosis:
•Loweredresistance(AIDS)andincreased
hypersensitivityofthehost,thehealedlesions
ofPrimarytuberculosismaygetreactivated.
•Thebacillilyingdormantinacellularcaseous
materialorhealedlesionareactivatedandcan
causesecondaryTB.

31. Secondary Tuberculosis
•Theinfectionofanindividualwhohasbeen
previouslyinfectedorsensitizediscalled
–SecondaryTB,or
–Post-Primaryor
–Reinfectionor
–ChronicTuberculosis.

32. The infection may occur from:
1.Endogenoussourcesuchasreactivationof
dormantprimarycomplex;or
2.Exogenoussourcesuchasfreshdoseof
Reinfectionbythetuberclebacilli.
•Secondarytuberculosisoccursmostcommonly
inlungs.
•Othersitesandtissueswhichcanbeinvolved
arelymphnodes,tonsils,pharynx,larynx,
smallintestineandskin.

33. •InfectionwithM.avium-intracellulareoccurs
morefrequentlyincasesofAIDS.
•PatientswithHIVinfectionpreviously
exposedtotuberculousinfectionhave
particularlyhighincidenceofreactivationof
primarytuberculosis.

34. Morphological Features of Secondary TB
•Thelesionsinsecondarypulmonary
tuberculosisusuallybeginas1-2cmapical
pleura.
•Itoccursbylymphohaematogenousspreadof
infectionfromprimarycomplextotheapexof
theaffectedlungwheretheoxygentensionis
highandfavourableforgrowthofaerobic
tuberclebacilli.
•Thepatternoflesionsinsuchcasesissimilar
tothatofprimarytuberculosis.

35. FATE OF SECONDARY PULMONARY TUBERCULOSIS
1.Thelesionsmayhealwithfibrousscarring
andcalcification.

36. 2.Thelesionsmayproduceprogressive
secondarypulmonarytuberculosiswiththe
followingpulmonaryandextrapulmonary
involvements:
i) Fibrocaseous tuberculosis
ii) Tuberculous caseous pneumonia
iii) Miliary tuberculosis
iv) Tuberculous empyema

37. FIBROCASEOUS TUBERCULOSIS:
•Theoriginalareaoftuberculousundergoesperipheral
healingandmassivecentralcaseationnecrosiswhich
may:
SOFT CASEOUS LESION WITHOUT
DRAINAGE INTO A BRONCHUS OR
BRONCHIOLE TO PRODUCE A
NON-CAVITARY LESION
(CHRONIC FIBROCASEOUS
TUBERCULOSIS).
BREAK INTO A BRONCHUS
FROM A CAVITY
(CAVITARY OR OPEN FIBROCASEOUS
TUBERCULOSIS)

38. CAVITARY OR OPEN FIBROCASEOUS
TUBERCULOSIS
CHRONIC FIBROCASEOUS
TUBERCULOSIS

39. PROGNOSIS OF CAVITARY OR OPEN FIBROCASEOUS TUBERCULOSIS
The cavity may communicate with bronchial tree and becomes
the source of spread of infection
(‘OPEN TUBERCULOSIS’).
May implant tuberculous lesion on the mucosal
lining of air passages producing
ENDOBRONCHIAL
AND ENDOTRACHEAL TUBERCULOSIS .
Ingestion of sputum containing
tubercle bacilli from
endogenous pulmonary lesions
may produce
LARYNGEAL AND
INTESTINAL
TUBERCULOSIS.

40. ENDOTRACHEAL TUBERCULOSIS
INTESTINAL TUBERCULOSIS
LARYNGEAL
TUBERCULOSIS

41. TUBERCULOUS CASEOUS PNEUMONIA
•Thecaseousmaterialfromacaseofsecondary
tuberculosisinanindividualwithhighdegreeof
hypersensitivitymayspreadtorestofthelung
producingcaseouspneumonia

42. MILIARY TUBERCULOSIS
•Thisislymphohaematogenousspreadof
tuberculousinfectionfromprimaryfocusorlater
stagesoftuberculosis.
•Thespreadmayoccurtosystemicorgansor
isolatedorgan.
•Thespreadiseitherbyentryofinfectioninto
pulmonaryveinproducingdisseminatedor
isolatedorganlesionindifferentextra-pulmonary
sites(e.g.liver,spleen,kidney,brain,meninges,
genitourinarytractandbonemarrow).

45. TUBERCULOUS EMPYEMA
•Thecaseatingpulmonarylesionsof
tuberculosismaybeassociatedwithempyema.
•Empyemamayhealbyfibrosisandobliterate
thepleuralspace(thickenedpleurabychronic
pleuritis).
•Occasionally,pleuralcavitymaycontain
caseousmaterialanddevelopintotuberculous
empyema.

46. TUBERCULOUS EMPYEMA
•Thecaseatingpulmonarylesionsof
tuberculosismaybeassociatedwithempyema.
•Empyemamayhealbyfibrosisandobliterate
thepleuralspace(thickenedpleurabychronic
pleuritis).
•Occasionally,pleuralcavitymaycontain
caseousmaterialanddevelopintotuberculous
empyema.

47. EMPYEMA

48. Clinical Features:
SYSTEMICFEATURES:
•FEVER,NIGHTSWEATS,FATIGUE,LOSSOF
WEIGHTANDAPPETITE.
REFERABLETOLUNGS:
-PRODUCTIVECOUGH
-HAEMOPTYSIS,
-PLEURALEFFUSION,
-DYSPNOEA,
-ORTHOPNOEAetc.

50. Diagnosis of Tuberculosis
•Thediagnosisismadebythefollowingtests:
i)AFBmicroscopyofdiagnosticspecimen
suchassputum,aspiratedmaterial.

51. ii)Mycobacterialculture:Traditionalmethod
onLJmediumfor4-8weeks.

52. iii)Molecularmethods-PCR.
iv)CompleteHaemogram-Lymphocytosis
andraisedESR.
v)Radiographicprocedurese.g.chestX-ray
showingcharacteristichilarnodulesandother
parenchymalchanges).

53. vi)Mantouxskintest:
•Thistestisdonebyintradermalinjectionof
0.1mloftuberculoprotein,purifiedprotein
derivative(PPD).

54. Delayedtypeofhypersensitivitydevelopsinindividuals
whoarehavingorhavebeenpreviouslyinfectedwith
tuberculousinfectionwhichisidentifiedasanindurated
areaofmorethan15mmin72hours.

55. •Thetestmaybe
•FALSEPOSITIVE:
-inatypicalmycobacterialinfectionand
-previousBCGvaccination,
•FALSENEGATIVE:
-inweakenedimmunesystem.
-sarcoidosis,
-someviralinfections,
-Hodgkin’sdisease,
-Recenttuberculous(8-10weeksofexposure)infection

56. CAUSESOFDEATHINPULMONARY TUBERCULOSIS
•Pulmonaryinsufficiency,
•Pulmonaryhaemorrhage,
•Sepsisduetodisseminatedmiliary
tuberculosis,
•CorPulmonale
•SecondaryAmyloidosis.