pathogenesis tb

7/29/2019 Pathogenesis TB

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Pathogenesis TB In

Children

HMS Chandra Kusuma

Pediatric Departement Of Fac. Med. Brawijaya Univ.

Saiful Anwar General Hospital


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Definition

Tuberculosis is a disease due toMycobacterium tuberculosis

infection with systemic spread thuscan affect almost all organs, andthe most frequent site is in the

lung, which usually as the site ofprimary infection


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Tuberculosis

The reaction of the tissues of the

human host to the presenceand multiplication ofMycobacterium tuberculosisor

Mycobacterium bovis


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History ancient Egypt : gibbus

1882, Koch, identification

management : sanatorium, collapsetreatment

Chemotherapy : PAS 1943 Lehmann

Streptomycine 1945 - Waksman & Schats

Isoniazid 1952 Domagk

Rifampicine - 1957


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Magnitude of problem

TB one of the oldest diseases of human

remains one of the deadliest diseases in

the world 8 million of new cases yearly

3 million death yearly

20-40% population is infected reemergence, global emergency


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The secret

Why TB is so strong & robust?

the secret: specific characters of

the bacilli special issues:

hematogenic spread

infection vs disease

primary vs post-primary


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Etiology


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The bacilli Mycobacterium tuberculosis Mycobacterium bovis

features:

slender, often slightly curved, rods aerobic, non-motile, non-spore forming

acid fail to wash the stain out acid fast bacilli

Mycobacteria : found in environments, somestrictly human pathogen (M tb, bovis), othersanimal pathogen and opportunistic pathogens inhuman (atypical mycobacteria)


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TB bacilli


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M tuberculosisUnique characteristics :

1. live in weeks in dry condition

2. no endotoxins, no exotoxins

3. hematogenic spread

4. grows slowly (24-32 hr)

5. non specific clinical manifestation6. aerob, organ predilection - lung

7. wide spectrum of replication: dormant


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Transmission


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Transmission ...

airborne human to human transmission bydroplet nuclei

adult pulmonary TB: cough, sneeze, speak, orsing

droplet nuclei : contain 2-3 bacilli, small size(1-5) keep in the air for long period

inhalation, reach alveoli

middle and lower lobes


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TB droplet nuclei


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Transmission factors:

doses / numbers

concentration in the air virulence

exposure duration

host immune state


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Infection source

Known source of infection, has

diagnostic value

Shaw (1954), transmission rate:AFB (+) : 62.5 %

AFB (-), M tb (+) : 26.8 %

AFB (-), M tb (-) : 17.6 %


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Transmission rate(Shaw 54)adult

TB patient

AFB(+)AFB(-)

culture(+)culture(-)CXR (+)

65% 26% 17%


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Pathogenesis


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Location of primary focus

in 2,114 cases, 1909-1928

Location %

Lung 95.93

Intestine 1.14

Skin 0.14Nose 0.09

Tonsil 0.09

Middle ear (Eustachian tube) 0.09Parotid 0.05

Conjunctiva 0.05

Undetermined 2.41


19/39Figure. Pathogenesis of primary tuberculosis

droplet nuclei

inhalation

alveoli ingestion by PAMS

intracellular replication

of bacilli

destructionof bacillidestruction of PAMS

Tubercle formation Hilar lymph nodes

hematogenic spread

multiple organsremote foci

Lymphogenic spread

disseminated primary TB

acute hematogenicspread

occult hematogenicspread

primary focus lymphangitis lymphadenitis

primary

complex

CMI

Pathogenesis


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PathogenesisM tuberculosisinoculation

phagocytocis by PAMM tbdestroyed

M tbsurvive, replicate

primary focus formation

lymphogenic spread

hematogenous spread

primary complex

CMI (+)

complication of:(1)primary complex, (2)lymphogenic

and (3)hematogenous spreadoptimal immunity

TB disease TB infection

death cured TB disease

tuberculin test (+)

primaryTB

postprimary

TB

reactivation

/ reinfection

incubationperiod

2-12weeks


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Incubation period

first implantation primary complex

4-6 weeks (2-12 weeks) incubation period

first weeks: logaritmic growth, : 103-10

4

elicit cellular response

end of incubation period:

primary complex formation

cell mediated immunity tuberculin sensitivity

Primary TB infection has established


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Hematogenous spread

during incubation period, before TBinfection establishment:

lymphogenic spread hematogenic spread

hematogenic spread (HS):

occult HS acute generalized HS


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Occult HS

most common sporadic, small number

no immediate clinical manifestation

remote foci in almost every organ rich vascularization: brain, liver, bones &

joints, kidney

including: lung apex region (Simon focus)

CMI (+): silent foci - dormant, potential forreactivation


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lymphadenitis

lymphangitis

primary focus

Pathogenesis...

Ghon focus

Simon focus


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TB hematogenous spread


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Acute HS

less common

large number

immediate clinical manifestation:disseminated TB

milliary TB, meningitis TB

tubercle in same size, specialappearance in CXR


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Miliary TB


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Primary complex

end of incubation period

TB infection establishment

tuberculin sensitivity (DTH)

cell mediated immunity

end of hematogenic spread

end of TB bacilli proliferation

small amount, live dormant in granuloma

new exogenous TB bacilli: destroyed / localized


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TB infection & TB disease

TB infection: CMI can control infection

primary complex (+)

cell mediated immunity (+)

tuberculin sensitivity (DTH) (+)

limited amount of TB bacilli

no clinical or radiological manifestation

TB disease:CMI failed to control TB infectionTB infection + clinical and/or radiologicalmanifestation


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TB infection

TB CMI


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TB disease

TB

CMI


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TB classification(ATS/CDC modified)Class Contact Infection Disease Treatment

0 - - - -

1 + - - proph I

2 + + - proph II?

3 + + + therapy


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TB natural history overview

primary TB infection

primary TB disease latent TB infection

no diseasepost primary TB

respiratory TBnon respir TB

new infection


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Prognostic factors

A. TB bacilli : virulence infection dose

B. Patient : general condition

age

nutritional state

coinfection: morbili, pertussis genetic

stress; physically (trauma, surgery) ormentally


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Pathology


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Pathology

complicated pathogenesisvaried pathology

clinical manifestation

radiologic appearance lung represent

tubercle, granuloma, tuberculoma, fibrosis,

fistula, cavity, atelectasis complication of primary focus: so many

possibilities


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Lesions of pulmonary TB

Parenchym: primary focus, pneumonia,atelectasis, tuberculoma, cavitary

Lymph node: hilar, paratracheal, mediastinal

Airway: air trapping, endobronchial TB,bronchial stenosis, fistula, bronchiectasis

Pleura: effusion, fistula, empyema,

pneumothorax, hemothorax Blood vessels: milliary, hemorrhage


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tubercle formationresolution

primary focus

calcification

2nd lung lesions

caseation

liquefaction

granuloma

Pathology jungle

remote focireg lymph node

tuberculoma

cavity

milliary seed

erodes airway

compresses airway

rupt to pleura rupt to airwaybronchiectasis

fibrosis

br pl fistula


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Thank you

pathogenesis tb

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