pathology inflammation

1. TUBERCULOSIS

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

3. Introduction:
• It is a Chronic Granulomatous inflammatory
infectious disease caused by Mycobacterium
tuberculosis in humans.

4. Etiology:
CAUSATIVE ORGANISM
• Tubercle bacillus or Koch’s bacillus called
Mycobacterium tuberculosis causes tuberculosis in
the lungs and other tissues of the human body.
• The organism is a strict aerobe and thrives best in
tissues with high oxygen tension such as in the apex
of the lung.
• Out of various pathogenic strains for human disease
included in Mycobacterium tuberculosis complex,
currently the most common is M. tuberculosis
hominis (human strain).

5. • M. tuberculosis bovis (bovine strain) used to
be common pathogen to human beings during
the era of consumption of unpasteurised milk
but presently constitutes a small number of
human cases
• Infection with M. avium-intracellulare (avian
or bird strain) is common in patients with
HIV/AIDS

6. Risk Factors:
• More common in developing countries of Asia,
Africa and Latin America.
• Malnutrition.
• Inadequate medical care.
• Poverty.
• Crowding.
• Chronic debilitating conditions like uncontrolled
diabetes.
• Alcoholism and immunocompromised states.
• In the western countries, there has been a
resurgence of tuberculosis due to HIV-AIDS.

7. Mode of Transmission:
• Human beings acquire infection with tubercle bacilli
by one of the following routes:
1. Inhalation of organisms present in fresh cough
droplets or in dried sputum from an open case of
pulmonary tuberculosis.

8. 2. Ingestion of the organisms leads to
development of tonsillar or intestinal
tuberculosis.

9. 3. Inoculation of the organisms into the skin
may rarely occur from infected postmortem
tissue.

10. 4. Transplacental route results in development
of congenital tuberculosis in foetus from
infected mother and is a rare mode of
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
• The sequence of events which take place when
tubercle bacilli enters body:
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. • Within 10-14 days, the centre of the cellular mass
begins to undergo caseation necrosis, characterized
by cheesy appearance and high lipid content.
• This stage is called SOFT TUBERCLE which is the
hallmark of Tuberculous lesions
Caseation Necrosis

16. ***
• The soft tubercle which is a fully-developed
granuloma with caseous centre does not favour
rapid proliferation of tubercle bacilli.
• Acid-fast bacilli are difficult to find in these
lesions and may be demonstrated at the
margins of recent necrotic foci and in the walls
of the cavities.

17. Fate of Tubercles:
The fate of a granuloma is variable:
1. COLD ABSCESS:
- The caseous material may undergo liquefaction and
extend into surrounding soft tissues, discharging the
contents on the surface.
- This is called cold abscess although there are no pus
cells in it.

18. 2. SINUS TRACTS:
- In tuberculosis of tissues like bones, joints,
lymph nodes and epididymis, sinuses are
formed and the sinus tracts are lined by
Tuberculous granulation tissue.

19. 3. SIZE INCREASE:
- The adjacent granulomas may coalesce
together enlarging the lesion which is
surrounded by progressive fibrosis.

20. 4. CALCIFICATION & OSSIFICATION:
- In the granuloma enclosed by fibrous tissue,
calcium salts may get deposited in the caseous
material (dystrophic calcification) and
sometimes the lesion may even get ossified
over the years.
dystrophic calcification

21. Types of Tuberculosis:
• Infection with tubercle bacilli is of 2 main
types:
1. Primary Tuberculosis.
2. Secondary Tuberculosis.

22. 1. Primary Tuberculosis:
• The infection of an individual who has not
been previously infected or immunised is
called Primary Tuberculosis or Ghon’s
complex or Childhood Tuberculosis.

23. Sites:
• The most commonly involved tissues for
primary complex are:
- Lungs and Hilar lymph nodes.
• Other tissues which may show primary
complex are
- Tonsils and Cervical lymph nodes
- Small intestine and mesenteric lymph nodes.

24. Primary complex or Ghon’s complex
• Primary complex or Ghon’s complex is the lesion
produced in the tissue of portal of entry with foci in
the draining lymphatic vessels and lymph nodes.

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
- Enlarged hilar and tracheo-bronchial lymph nodes in the
area drained.
- The affected lymph nodes are matted and show caseation
necrosis.

27. Fate Of Primary Tuberculosis
• Primary complex may have one of the following
sequelae:
1. Fibrosis, Calcification and Ossification.

28. 2. Progressive primary tuberculosis:
• Caseous material is disseminated through
bronchi to the other parts of the same lung or
the opposite lung.

29. 3. Primary Miliary Tuberculosis:
• Bacilli may enter the circulation through
erosion in a blood vessel and spread by
haematogenous route to other tissues and
organs.
• The lesions may be seen in organs like the
liver, spleen, kidney, brain and bone marrow.

30. 3. Progressive Secondary Tuberculosis:
• Lowered resistance (AIDS) and increased
hypersensitivity of the host, the healed lesions
of Primary tuberculosis may get reactivated.
• The bacilli lying dormant in acellular caseous
material or healed lesion are activated and can
cause secondary TB.

31. Secondary Tuberculosis
• The infection of an individual who has been
previously infected or sensitized is called
– Secondary TB, or
– Post-Primary or
– Reinfection or
– Chronic Tuberculosis.

32. The infection may occur from:
1. Endogenous source such as reactivation of
dormant primary complex; or
2. Exogenous source such as fresh dose of
Reinfection by the tubercle bacilli.
• Secondary tuberculosis occurs most commonly
in lungs.
• Other sites and tissues which can be involved
are lymph nodes, tonsils, pharynx, larynx,
small intestine and skin.

33. • Infection with M. avium-intracellulare occurs
more frequently in cases of AIDS.
• Patients with HIV infection previously
exposed to tuberculous infection have
particularly high incidence of reactivation of
primary tuberculosis.

34. Morphological Features of Secondary TB
• The lesions in secondary pulmonary
tuberculosis usually begin as 1-2 cm apical
pleura.
• It occurs by lymphohaematogenous spread of
infection from primary complex to the apex of
the affected lung where the oxygen tension is
high and favourable for growth of aerobic
tubercle bacilli.
• The pattern of lesions in such cases is similar
to that of primary tuberculosis.

35. FATE OF SECONDARY PULMONARY TUBERCULOSIS
1. The lesions may heal with fibrous scarring
and calcification.

36. 2. The lesions may produce progressive
secondary pulmonary tuberculosis with the
following pulmonary and extrapulmonary
involvements:
i) Fibrocaseous tuberculosis
ii) Tuberculous caseous pneumonia
iii) Miliary tuberculosis
iv) Tuberculous empyema

37. FIBROCASEOUS TUBERCULOSIS:
• The original area of tuberculous undergoes peripheral
healing and massive central caseation necrosis which
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
• The caseous material from a case of secondary
tuberculosis in an individual with high degree of
hypersensitivity may spread to rest of the lung
producing caseous pneumonia

42. MILIARY TUBERCULOSIS
• This is lymphohaematogenous spread of
tuberculous infection from primary focus or later
stages of tuberculosis.
• The spread may occur to systemic organs or
isolated organ.
• The spread is either by entry of infection into
pulmonary vein producing disseminated or
isolated organ lesion in different extra-pulmonary
sites (e.g. liver, spleen, kidney, brain, meninges,
genitourinary tract and bone marrow).

45. TUBERCULOUS EMPYEMA
• The caseating pulmonary lesions of
tuberculosis may be associated with empyema.
• Empyema may heal by fibrosis and obliterate
the pleural space (thickened pleura by chronic
pleuritis).
• Occasionally, pleural cavity may contain
caseous material and develop into tuberculous
empyema.

46. TUBERCULOUS EMPYEMA
• The caseating pulmonary lesions of
tuberculosis may be associated with empyema.
• Empyema may heal by fibrosis and obliterate
the pleural space (thickened pleura by chronic
pleuritis).
• Occasionally, pleural cavity may contain
caseous material and develop into tuberculous
empyema.

47. EMPYEMA

48. Clinical Features:
SYSTEMIC FEATURES:
• FEVER, NIGHT SWEATS, FATIGUE, LOSS OF
WEIGHT AND APPETITE.
REFERABLE TO LUNGS:
- PRODUCTIVE COUGH
- HAEMOPTYSIS,
- PLEURAL EFFUSION,
- DYSPNOEA,
- ORTHOPNOEA etc.

50. Diagnosis of Tuberculosis
• The diagnosis is made by the following tests:
i) AFB microscopy of diagnostic specimen
such as sputum, aspirated material.

51. ii) Mycobacterial culture: Traditional method
on LJ medium for 4-8 weeks.

52. iii) Molecular methods- PCR.
iv) Complete Haemogram- Lymphocytosis
and raised ESR.
v) Radiographic procedures e.g. chest X-ray
showing characteristic hilar nodules and other
parenchymal changes).

53. vi) Mantoux skin test:
• This test is done by intradermal injection of
0.1 ml of tuberculoprotein, purified protein
derivative (PPD).

54. Delayed type of hypersensitivity develops in individuals
who are having or have been previously infected with
tuberculous infection which is identified as an indurated
area of more than 15 mm in 72 hours.

55. • The test may be
• FALSE POSITIVE:
- in atypical mycobacterial infection and
- previous BCG vaccination,
• FALSE NEGATIVE:
- in weakened immune system.
- sarcoidosis,
- some viral infections,
- Hodgkin’s disease,
- Recent tuberculous (8-10 weeks of exposure) infection

56. CAUSES OF DEATH IN PULMONARY TUBERCULOSIS
• Pulmonary insufficiency,
• Pulmonary haemorrhage,
• Sepsis due to disseminated miliary
tuberculosis,
• Cor Pulmonale
• Secondary Amyloidosis.