2. Tb Pathology English

8/10/2019 2. Tb Pathology English

1/86

2. TuberculosisPathogenesis

PathologyProf. Dr. Gabriela Jimborean


2/86

TB infection == TB disease

Infection is associated with TB disease - in 10%

Risk Factorswho det. progression of infectionto active disease are multipleand depend on:

Abundancein BK of the sourceVirulence ()

Intimacy and durationof the contact ()

Dicrease in immunologicaldefense of the host


3/86

Events in naive host ( not

immunised)

Non immune defence

of the host

BK exposure

Superior Resp tract.(nose)

retains particles of sputum from10 to 500 microniBronchimucociliary clearanceAlveoli - BKphagocytosisby

alveolar macrophages

BK are trasported to the largebronchi, trachea - cough -elimination

Donaldson et al 2007, Bennett et al 2010In-Vivo Measurements of Mucociliary and Cough Clearance
http://www.med.unc.edu/cemalb/mucociliary-clearance/files/publications-pdf/ProcATS_MCC.pdfhttp://www.med.unc.edu/cemalb/mucociliary-clearance/files/publications-pdf/WorkshopFinal.pdfhttp://www.med.unc.edu/cemalb/mucociliary-clearance/files/publications-pdf/WorkshopFinal.pdfhttp://www.med.unc.edu/cemalb/mucociliary-clearance/files/publications-pdf/ProcATS_MCC.pdf


4/86

Natural Immunisation

Nonimune defense

Suitable

In 70% No Infection

Unsuitable defense or

repeted close contacts

30% Primary TB infection

Non specificImmuneresponse

Specificimmune response= Normal 95%Latent infection

Specific immuneresponse

UnsuitableSpecific Immune response5% Primary TB disease

Recovery +Latent infection

Cellular immunitydevelopment+/- treatment

Decreased immunity +/- over BK infectionLate secondary TB disease reactivation 5%

BK

BK

Ag BK

Variable interval

Over BK infection


5/86

90%


6/86

Pathogenesis

BK multiplicate after deep penetration in the lung

1. Nonspecific inflammation(Congestion, edema, exudate fibrinneutrophils, Eo, Ly)

(BK cannot be destroied)

2.Ag-presenting cells+LyT deliver chemotactic factorsfor Mo,Mf, ly

3. Mf takethe BK and transport them in the lymph vesselsand lymph nodes

3. Specific inflammation- primary TB Complex

Will be installed:Delayed hypersensitivity type IV cell-mediatedresponseLy-Mf

(= Ag recognition + Reaction)Protective cellular immunity Ly-Mf

(= Defense capability through effective BKlysis and granuloma formation)


7/86

Primary TB Complex

1.Primary Afect

+ passing of the BK in the lymph

vessels and nodes

2. Hilar limph node

3.Spontaneous healing+ fibrous

sequeles +Ca++ sleeping germs

Newly acquired reactivity stop the

germs multiplication + positive PPD

4.+/- Vascular Disseminationto other

organs (in immunocompromised

hosts) miliary TB

exprarespiratory TB


8/86


9/86

Sensibilisation and immune reaction

Under the Ag, TLy are activated, they sensitize +

blastic transformation -- more subsets of Ly

1. T Ly +immune memory+ longevity(LyT CD4)

2. T Ly secreting lymphokines(LyT CD4) -

(mediators that modulate IR)

CD4 T Lyseveral roles

- trigger the delayed hypersensitivity

- Mf activation and protective immunity- Chemotactic factors- INF- secretion - Tumor Necrosis Factor

secretion by the Mf


10/86

CD4 Ly

-T helper 1 cytokine-producer - INF-(role in

cell immunity for intracellular germs ex. BK)

- T helper 2- IL 4, IL 5 cooperation with Ly B

and Ig production

CD8 T Ly- lymphotoxine - role in immunological

cytolysis = Ag cell recognition and targetdestruction


11/86

Ag BK

small

amount

LyT Sensibilisation MemoryLyLymphokine producerLy

Blastictransforming

of otherLy

Increase Ag

information

Ly

Lymphokine releaser

Transforming

Activation of Mf

TNF

INF

Activation of Mf, phagocytosis,necrosis production

FTBFIMMf

Chemotactic F.

Mf, Ly, Mo

Granuloma

TB

Ag.

Presenting

cell

IL6

LyB

AMf.F


12/86

Tissue lesionsare the "price" to pay for

BK intracellular presence and

multiplication (Mf Ly produce BK

invaded cell destruction)

Immune response magnitude depends on:- number BK

- intensity of awareness

- genetic control of immune response


13/86

Activated Mf(by lymphokines or by stimulating Ag)

become epithelioid and Langhans multinucleated giant

cells (rich in lysosomes, mitochondria, lytic enzymes)

Secrete cytokines that activated Mf:

TNF- has a protective role in infection by the activation of the

Mf cells, phagocytic necrosis and granuloma formation

If infection is largea great TNF- release -- hight toxic

effects(fever, fatigue, consumption, demineralization,

cachexia)

Interleukins- role in Ly activation, T, B, NK "Natural Killer"


14/86

Caseous Necrosis = Immunological mediatedcytolysis = Ly + Mf and Ac-dependent cell (N

killer) destroy target cell ( infected with BK)

Inside the granuloma

AnoxiaAcidosis

Toxic products of granuloma

Macrophages in cooperation with Ly

inhibits proliferation and make BK lysis


15/86

Liquefaction of caseation necrosis formscavities containing enormous numbers of TB

bacilliIsolation of the germs inside the granuloma

prevents dissemination

If the Imun Response is modest

Bk can survivein sleeping mode long timeinside granuloma

BK may be circulatedto other sites with Mf

BK multiply and destroytissue and makeextended necrosis


16/86

Granulomatous inflammatoryprocess

- Caseous necrosis(white -yellow, acidic pH )- 1-2 Langhans giant cells

(activated Mf)- Epithelioid cell (activated Mf)

Around the periphery of thegranuloma

- T Ly

- Fibroblasts- Collagen fibers

- some PMN

TB Granuloma


17/86

Inflammatory reactions can be very pronounced:- perifocale pleuro-pulmonary congestion

(epituberculosis)- extensive caseous necrosis by

Delayed Cell-mediated hypersensitivity(PPD test shows the presence of cell hypersensibility)

Their moderation occurs when:- effectively germs are destroied (with in Ag

stimulus)

- fibrogenetic reactions ( Ca +)

Healing = expression of installation of the

Protective cellular immunity


18/86

Primary TB Hilar and

paratraheal AdenopatyPrimary TB

Child with HIVinf./AIDS


19/86

Langhans giant cell


20/86

BK Microscopy

AFB- Ziehl Neelsen

M. Tuberculosis colonies

Lwenstein Jensen


21/86

Multinucleated

Langhans cell

Tb Granuloma


22/86

Right Hilar Adenopaty

Epituberculosis +atelectasis by

compresion

Limph nodes perforation

and bronchial spreadExtended Necrosis with

primary cavitation


23/86

Cellular immunity in TB

Is protective: Prevents passage of the primary infectionto manifest

disease Prevents complications and dissemination Provides resistance to other breakthrough BK

Is relatively: It does not fully exclude the disease when exist immuno-

supresive factors (repeated massive infection, risk F.)

Is a "superinfection" conditioned by the persistence of infection in the body or

new "boosters" (to keep infection active by Ag stimulus)

Sterilization infection(rare in humans) leads to extinctionHSI, immunity and previous positive PPD test negativity


24/86

Cellular immunity in TB (2 components)

1). Natural immunity- by factors of resistance (LyT

and Mf native qualities) selected and genetically

transmitted, derived from the experience of previous

generations in contact with TB

2).Acquired Immunity- in the current generation

experience by:

- Recent contact with TB patients

- BCG vaccination

- Cross Immunization by infection with MNT (spread

in the external environment)


25/86

Tests of the cellular immunity

Tuberculinic skin testmigration of theactivated cells

Quantiferon TB GOLDdelivery in serrumof the INF gama produced by theactivated TLy


26/86

Humoral immunity in TB

Development of Ig versus various bacillary Ag

Lack of protective role of humoral immunity in TB

But.....There is cooperationwith cell immunity

Highlighting some Ab - humoral "markers"we

can see active disease in the early stagesEx. TB meningitis


27/86

Pathology TB


28/86

Specific TB Inflammation and lesions

3 Components (exudative, necrotic, proliferative)

which importance depends on:

- size and virulence of infection- location of the injury (serous, parenchyma)

- risk factors

- eficiency of the installed immunity

- treatment


29/86

1. Exudative processeSerum extravasation (fibrin) + cells

The exudation

At the level of pleura, peritoneum, pericardum

Big amount even in the presence of a small no. of BK

Build during the maximum DHS periode =epituberculosis(congestion,

pleurisy, peritoneal reaction )

It may initially resolve when no necrosis occurred

By chronic evolution - Fibrin will be organized in connectivefibrous tissue -

scars


30/86

2. Dystrophic lesions

1. Simple dystrophy

2. Tissue Necrosis + inflammatory cells

necrosis + BK necrosis

specific caseous necrosis


31/86

Proliferation in

mesenchymal tissue

migrated cells from blood - Ly, Mo (Mf)

connective fibers

Proliferative granulative - fibrousreaction and caseous necrosis are alwaysassociated

- Confer specificity to the TB inflammation

- Try to limit the extension of the lesions

3. Proliferative lesions


32/86

TB granuloma(1)

- Caseous necrosis(white - yellow, acidic pH )

- 1-2 Langhans giant cells (activated Mf)

- Epithelioid cell (activated Mf)

Around the periphery of the granuloma- T Ly

- Fibroblasts

- Collagen fibers

- some PMN


33/86

TB granuloma (2)

Granuloma are avascular structuresIn development:

They extend, confluence with neighboring nodes

tubers " follicles and produce extended lesions:nodules, infiltrates, cavities

+ / - Dissemination

+ Sleeping bacilli persist in fibrous sequelae (with

reactivation potential)


34/86

TB Granuloma


35/86

TB granuloma in

lung

Normal lung


36/86

Differential diagnosis of TB granuloma


37/86

Leprae


38/86

Aspergillus


39/86

Sarcoidosis (without necrosis, noconfluence)
http://www.granuloma.homestead.com/files/sarcoid_lunginv67.jpg


40/86

Foreign body Granuloma - silicon


41/86

Vegetal foreign body Granuloma


42/86

Bone necrosis + cazeum+ fibrous reactions
http://rds.yahoo.com/_ylt=A9iby4NalFxFoEAB03eJzbkF;_ylu=X3oDMTBkZG5udXMwBHBvcwMyMgRzZWMDc3I-/SIG=1eq3e98dq/EXP=1163781594/**http%3a//images.search.yahoo.com/search/images/view%3fback=http%253A%252F%252Fimages.search.yahoo.com%252Fsearch%252Fimages%253Fp%253DPott%252BDisease%2526ei%253DUTF-8%2526fr%253Dieas%2526b%253D21%26w=470%26h=351%26imgurl=www.skhchest.org%252FCASE%252FCase69%252FCT.jpg%26rurl=http%253A%252F%252Fwww.skhchest.org%252FCASE%252FCase69%252Fcase69.htm%26size=32.1kB%26name=CT.jpg%26p=Pott%2bDisease%26type=jpeg%26no=22%26tt=69%26oid=09a5d59233eba18a%26ei=UTF-8http://rds.yahoo.com/_ylt=A9ibyGUblFxFp0YBtNWJzbkF;_ylu=X3oDMTBkbmplZzd2BHBvcwMxNARzZWMDc3I-/SIG=1focrcfio/EXP=1163781531/**http%3a//images.search.yahoo.com/search/images/view%3fback=http%253A%252F%252Fimages.search.yahoo.com%252Fsearch%252Fimages%253Fp%253DPott%252BDisease%2526ei%253DUTF-8%2526fr%253Dieas%2526x%253Dwrt%26w=416%26h=683%26imgurl=www.mevis.de%252F%257Ehhj%252FLunge%252Fima%252FTbSpondyl.JPG%26rurl=http%253A%252F%252Fwww.mevis.de%252F%257Ehhj%252FLunge%252FxSammlungInfFr.html%26size=23.5kB%26name=TbSpondyl.JPG%26p=Pott%2bDisease%26type=jpeg%26no=14%26tt=69%26oid=aae05a640a3c6abe%26ei=UTF-8


43/86

Spinal TB

Extended Necrosis with


44/86

Extended Necrosis with

infiltrates, noduli and

secondary cavitation, (left

uper lobe)Extended Necrosis ( right uper lobe)

with infiltrates noduli and

(left uper lobe)


45/86

Cavitary TB , antracosis


46/86

Healed, with epitelium cavity after TB


47/86

Cavity with blood clot


48/86

Aspergiloma


49/86

Miliary TB


50/86

Miliary TB


51/86

Peritoneal miliary TB


52/86

Limph nodeTB


53/86

TB Orhiepididimitis

TB O hi ididi i i


54/86

TB Orhiepididimitis


55/86


56/86

Subpleural Tuberculoma

TB Sequelaes + Calcium


57/86

TB Sequelaes + Calciumdeposition, emphysema


58/86

Necrosis, cavities

Pneumothorax in bilateral


59/86

Pneumothorax in bilateralcavitary TB

P i i ht TB i t i


60/86

Primary right TB + gigant primary

tuberculoma


61/86

Primary right TB + hylar adenopaty + pleuritis

P i i ht TB + h l d t +


62/86

Primary right TB + hylar adenopaty +

pleuritis and epituberculosis

TB adenopathy compression on


63/86

TB adenopathy compression on

bronchial spur

B hi l fi t l


64/86

Bronchial fistula

Lymph node perforation in bronchus


65/86

Gangliobronchial fistulae after primar TB


66/86

Pulmonary miliary TB


67/86

Peritoneal TB

The main features of primary TB


68/86

The main features of primary TB

Predilection for younger ages

Strong hypersensitivityreactions associated

Always important involvement of the lymphatic

system

High potential for dissemination (even occult )

Spontaneous healing, except complicated shapes

BK persistencein post primary sequelaes with

possible secondary endogenous reactivation

Secondary TB


69/86

Secondary TB

5%of the latent infected people (after the I episode)

By reactivating endogenous or exogenous overinfection

Occurs at different time after ITB(continuing the I TB

or after years / decades)

Predilection for adults

Satellite adenopathy missing

Lymphatic and hematogenous dissemination (possiblebut not frequent)

Main organ involved - LUNG "pulmonary phthisis"

Extension by contiguity or canalicular


70/86

dissemination

Lesions have caseous necroticaspect

Trend to cavitation

+ Limitation by fibrosis

(missing in immunosuppressed)

Progressive, chronic,evolution

with relapses and remissions

with worsening in every spurt

without spontaneous healing

with multiple complications

high fatality


71/86

Healing

does not include sterilisation In most cases

Clinical cure

Radiological

Bacteriological

Bioumoral

with persistence of sleep bacilli in sequelae

= Persistent infection(documented by PPD + +

after cured disease)

Extensive bilateral secondary cavitary


72/86

Extensive bilateral secondary cavitaryTB - extensive necrosis - caverns,nodules of bronchogenic spread

Bilateral secondary cavitary TB


73/86

Bilateral secondary cavitary TB- Extensive necrosis

Chronic cavitary TB


74/86

Chronic cavitary TB

right fibrothorax

Drained pneumothorax


75/86

Drained pneumothorax

+ subcutaneus emphysema


76/86

Bronchial infiltrative lesions in TB

Fi l (l h d


77/86

Fistula (lymphnode

and bronchus)anthracosis

Scar stenosis

Fistulae


78/86

TB granuloma

Membranes with KB

Scar stenosis


79/86

Scar stenosis

Classification of TB


80/86

Classification of TBDepending on the time of TB evolutionary cycle:

Primary TB SecondaryTB

Depending on the location:Respiratory TB - pulmonary TB, pleuresy

Extrarespiratory TB - Joint TB, genital, digestive, etc

Respiratory and extrarespiratory


81/86

Extrarespiratory TB

Limph nodes TB

Scapulohumeral TB

Rib TB


82/86

PottsDisease

PottsdiseaseLytic destruction of anteriorportion of vertebral body

Necrosis +paravertebral abscess
http://rds.yahoo.com/_ylt=A9iby4TvlVxFDuoAiTqJzbkF;_ylu=X3oDMTBkaWRnNHZyBHBvcwMxMQRzZWMDc3I-/SIG=1gde96pup/EXP=1163781999/**http%3a//images.search.yahoo.com/search/images/view%3fback=http%253A%252F%252Fimages.search.yahoo.com%252Fsearch%252Fimages%253Fp%253DPott%252527s%252BDisease%2526ei%253DUTF-8%2526fr%253Dieas%2526x%253Dwrt%26w=407%26h=305%26imgurl=www.reumatologiahvh.org%252Fgaleria%252Fimg%252F320.jpg%26rurl=http%253A%252F%252Fwww.reumatologiahvh.org%252Fgaleria%252FING_ampliar_datos.asp%253FFOTO%253D320%26size=11.4kB%26name=320.jpg%26p=Pott%2527s%2bDisease%26type=jpeg%26no=11%26tt=60%26oid=2d2844c27467dac4%26ei=UTF-8


83/86

TB Pericarditis

Skin TB
http://images.google.ro/imgres?imgurl=http://www.fujita-hu.ac.jp/~tsutsumi/image/163/3.jpg&imgrefurl=http://www.fujita-hu.ac.jp/~tsutsumi/case/case163.htm&h=400&w=600&sz=81&hl=ro&start=28&tbnid=rPIFK8feosHPxM:&tbnh=90&tbnw=135&prev=/images%3Fq%3DTuberculosis%26start%3D20%26ndsp%3D20%26svnum%3D10%26hl%3Dro%26lr%3D%26sa%3DN


84/86

Renal TB

Hydroureter+ multistage

stenosis

T b l O hi ididi iti


85/86

Tuberculous Orhiepididimitis

I t ti l TB Addi Di


86/86

Intestinal TB Addisons DiseasesAdrenal gland TB

2. Tb Pathology English

Documents