This is a presentation on the pathophysiology Tuberculosis , Mechanism of infection and inflammation involved in the disese process

2. Tuberculosis (TB) is an ancient disease with a
history interwoven with the evolution and
migration of mankind.
Mycobacterium tuberculosis is thought to have
evolved from an early progenitor in East Africa as
early as 3300 years ago.
By the early 1800s, TB epidemics ravaged much of
Europe and North America, resulting in 800 to
1000 deaths per 100 000 population per year.

3. 1700 s TB was called as white
plague.
Until mid-1800s, many believed
TB was hereditary (vampire
panic).
1834 Johann schonlein coined the
term tuberculosis.
1865 Jean Antoine-Villemin
proved TB was contagious.
1882 Robert Koch discovered M.
tuberculosis, the bacterium that
causes TB.
1943 Selman Waksman
developed streptomycin in the
treatment of TB. 3

4. India is the highest TB burden
country in the world
10.6 million people affected
with TB in 2022 globally with
almost 1.6 million deaths related
to TB.
In India 2.59 million affected
with TB, 188 per 1 lakh
population in 2022.
Globally, about 1 million cases
of paediatric TB estimated with
mortality of about 1 lakh .

5. It is a chronic specific inflammatory infectious disease
caused by mycobacterium tuberculosis in human.
Usually attacks the lungs(pulmonary) but it can also
affect any parts of the body (extra pulmonary).
Organism dormant for decades(latent TB).
Reactivation of disease occurs when Immune defenses
lowers and become communicable disease.
5

6.  Crowded living condition
 Malnutrition
 Smoking
 Malignancy
 Old age
 Diseases weakens immune system – AIDS
 Immuno supressive drugs – steroids , TNF
antagonists
 Systemic diseases – DM,CRF,CLD
 Genetic susceptibility –TLR deficiency,
IFN deficiency

7.  AEROSOL
 INGESTION
 INOCULATION

8. Infected persons with active TB release the
bacteria in air by cough, sneeze, speak, spit.
A single sneeze can release upto 40,000
infectious droplets but even 10 bacteria may
cause infection.
 Incubation period varies according to age and
risk factors
After 3-4 weeks of acquiring infection , person
becomes infectious to others.

9. Rod shaped (bacilli)
Slow growing
Non motile
Aerobic
0.2 -0.5µ in D 2-4µ in L
Acid fast bacilli

10. Mycolic acid responsible for
acid fastness
Prevention of
phagolysosome formation
Virulence
Resistant to drying ,
alkalinity/acidity &many
antibiotics

11. 1. Initial macrophage response
2. Replication of bacilli
3. Activation of immune response
4. Cavitation stage.

12. Early in infection—bacteria enters into airspaces
where through phagocyte receptors enter into
macrophages and multiply.

13. M. tuberculosis recruits a host protein coronin to the
membrane of the phagosome
Coronin activates the phosphatase calcineurin, leading
to inhibition of phagosome-lysosome fusion.
Inhibits maturation of the phagosome and blocks
formation of the phagolysosome.
Unchecked replication leads to bacteremia
and seeding of multiple sites.

15. Depends on
Number of organisms
inhaled
Virulence of the
organism
Immune status of the
host

16. Pathogen recognised by innate immune receptors
(TLR2 &TLR 9)
Lipoarabinomannan binds with TLR2 &TLR 9
↓
Enhances the innate & adaptive immune response
in TB

17. About 3 weeks after infection,
Mycobacterial antigens enter draining lymph nodes
displayed to T cells.
Differentiation of TH1 cells(secretion of IL-12 by
antigen presenting cells)
Stimulation of TLR2 by mycobacterial ligands
promotes production of IL-12 by dendritic cells.
T-helper 1 (TH1) response is mounted that activates
macrophages, enabling them to become
bactericidal.

19. Th1 cells produces IFN-γ
stimulates maturation of the phagolysosome in
infected macrophages,
expose the bacteria to a lethal acidic, oxidizing
environment
stimulates expression of inducible nitric oxide
synthase  NO, reactive nitrogen intermediates
mobilizes antimicrobial peptides (defensins) against
the bacteria
 stimulates autophagy

20.  IFN-γ differentiate macrophages into the
“epithelioid histiocytes” which forms granulomas
and Langhans giant cells
 In many people this response halts the infection
before significant tissue destruction or illness occur.
In other people the infection progresses due to
immunosuppression, and the ongoing immune
response results in caseation necrosis or tissue
destruction.

22.  Disease that develops in previously
unexposed person.
 Inhaled bacilli implant in the distal
airspaces of the lower part of upper
lobe or upper part of the lower lobe
 1 -1.5 cm area of grey white
inflammation with consolidation
develops , called as GHON’s
FOCUS, which often caseates
 Subpleural granuloma (parenchyma) +
hilar LN granuloma is called as
GHON’s COMPLEX

24.  Heal by fibrosis calcification
 Progressive primary tuberculosis
↓
 Primary miliary tuberculosis

25.  The infection of an
individual who has been
previously infected or
sensitized.
 The infection may be
acquired from
Endogenous source:
reactivation of dormant
primary complex.
Exogenous source.

26. Heal With Fibrous Scarring And
Calcification
Tuberculous Pneumonia
Secondary Progressive Pulmonary
Tuberculosis
Tuberculous Caseous Pneumonia
Fibro caseous Tuberculosis
Miliary Tuberculosis

27.  Gross: sharply
circumscribed, firm,
gray white to yellow
presents as
consolidation of <2 cm
D within apical pleura.
 Micro: coalescent
tuberculous granulomas
with central caseation
necrosis.

29.  Seen usually in elderly, immunosuppressed people
or untreated patients.
 Apical lesion enlarges with expansion of area of
necrosis forming cavity which may either
break into bronchus from a cavity with
evacuation of caseous material (open
fibrocaseous TB )
Break into blood vessel producing hemoptysis

30.  The cavity provides a favourable environment for
the proliferation of a bacilli due to high oxygen
tension
 The open case of secondary TB may implant
tuberculous lesion on the mucosal lining of air
passages producing endobronchial / endotracheal
TB

32.  Extension to pleura producing bronchopleural fistula
 Tuberculous empyema
 Thickened pleura
 Pleural effusions
 Obliterative fibrous pleuritis

33.  Occurs when organisms drain through lymphatics
into lymphatic ducts venous return on the right
side of heart pulmonary arteries
 Lymphatic spread – EB,ET AND LARYNGEAL TB
 Individual lesions are either microscopic or small,
visible (2mm) foci of yellow-white consolidation
scattered through the lung parenchyma (resembling
millet seeds)
 Micro: the lesion shows structure of granuloma with
minute areas of caseous necrosis.

35.  In tissues or organs seeded
haematogenously.
 Intestinal (Primary,
Secondary, Hyperplastic)
 Meninges (Tuberculous Meningitis )
 Kidneys ( Renal Tuberculosis )
 Adrenals (Addison’s Disease )
 Bone ( Osteomyelitis )
 Vertebrae ( Pott’s Disease )
 Fallopian Tube ( Salpingitis )

36. INTESTINAL TB MENINGEAL TB

37. SPLEEN LYMPH NODE

38. POTT’S SPINE TB KIDNEY

39. TB EPIDIDYMO ORCHITIS TB PERICARDITIS

40. TB is the leading cause of
death in AIDS.
Low CD4 count is the risk factor.
Pulmonary manifestations varies from focal lesion
to multiple infiltrates .
False negative sputum smears in seropositive
patients due to absence of bacterial cell wall
destruction as there is reduced T cell mediated
immune reaction.