Is a worldwide disease with 3 million death per year. Etiology and pathogenesis. Mycobacterium (M) is the etiologic agent of TB. It is an aerobic non spore forming non motile with waxy coat. It’s un acid fast bacilli due to this coat which attains the red color. The 2 species which cause the human TB are M tuberculosis, air borne and M bovis, transmitted with milk and affects the GI and tonsilla. The M avium and M intracellare rarely affect normal person and are important in AIDS affected individuals

1. TUBERCOLOSIS
• Is a worldwide disease with 3 million death per
year.
• Etiology and pathogenesis.
Mycobacterium (M) is the etiologic agent of TB. It
is an aerobic non spore forming non motile with
waxy coat. It’s un acid fast bacilli due to this coat
which attains the red color.
The 2 species which cause the human TB are M
tuberculosis, air borne and M bovis, transmitted
with milk and affects the GI and tonsilla. The M
avium and M intracellare rarely affect normal
person and are important in AIDS affected
individuals.

2. • The pathogenicity of the M is related to its
ability to escape macrophage killing and
induce delayed hypersensitivity and that is
due to several components on the cell wall:
cord factor (glycolipid which make M grow
in serpentine cord in vitro),

3. • Primary infection.
At the periphery of the lung, alveolar
macrophages transport the M to the Hilary
nodes. Native macrophages unable to kill
the M and kill the macrophages and
release the M which enter other
macrophages or sometimes disseminate
through the blood to other parts of the lung
or elsewhere in the body.

4. • After few weeks T-cell mediated immunity
develop and hence the appearance of the
skin reaction positivity.
• The M activated T-cells interact with
infected macrophages in 3 ways:
1. T helper cells (CD4) secrete INF-γ which
activate macrophages to kill the intracellular
M through reactive nitrogen intermediates
(NO, NO2, HNO3) This is associated with
the formation of epitheloid cell granuloma
and clearance of the M.

5. 2. Cytotoxic T cells (CD8+) lyse macrophages
infected with M through a Fas-independent,
granule-dependent reaction and kill the M.
3. CD4-, CD8- T cells lyse the macrophages in
a Fas-dependent reaction without killing the
M. the lyses of the macrophages results in
the formation of caseating granulomas
(delayed type hypersensitivity reaction.)
Direct toxicity of the M to the macrophage
may contribute the caseose necrosis center.
M cannot grow in the acidic extra cellular
environment lacking in oxygen and so the M
infection is controlled.

7. • Secondary infection:
This disease can occur with a reinfection
of new M, reactivation of a dormant lesion
or continuation of the primary infection
due to virulent M susceptibility of the host.
In mice susceptibility to M infection is
determined by an autosomal dominant
gene called Bcg which encode a
membrane transport protein but its
function is not clear.

10. • The granulomas in secondary tuberculosis occur
most often in the apex of the lung but can occur
everywhere in the disseminated form.
• The granulomas fail to contain the spread of the
infection and is the major cause of tissue damage in
T.B. And is also a reflection of delayed hyper
sensitivity.
• Caseose necrosis and formation of cavities is 2
special features of the secondary T.B. The caseose
necrosis may cause the rupture of the blood and
spread of M throughout the body and break the
airways releasing the M in aerosols.

11. • In the lung the secondary TB mostly
commonly affects the apex because it’s well
ventilated. In favorable cases, the initial
parenchyma focus develops a small area of
caseation necrosis that doesn’t form cavity
because fails to communicate to bronchus.
Progressive fibrosis encapsulate the focus
and formation of a raised or depressed scar
on the pleural surface and sometimes pleural
adhesion and secondary blackening.

12. • Histologically, coalescent granulomas
composed of epitheloid cells, few giant of
Langhans type and a layer of lymphocytes
and dense CT. At the center the mature
gramulomas contain caseose necrosis.
Together these form the tubercle. The
tubercles coalesce to create large area of
consolidation. In favorable cases the entire
area is converted into fibrocalcific scar or
walled off by hyaline CT while there is still the
caseose debris.

19. • The subsequent course of the secondary infection
is variable. The lesion may heal spontaneously or
with therapy with formation of fibrocalcific nodule.
In unfavorable cases may progress into of the 3
possible ways:
1. Cavitary fibrocaseous TB.
By erosion into bronchiole, drainage of the caseous
focus transforms into a cavity. The multiplication of
M is favored by the increase in oxygen tension. The
cavity, usually at the apex, is lined by a yellow-grey
caseous material and is walled off by CT. there are
some thrombosed arteries attraversing the cavity
(bridge).

20. • Further dissemination can occur through airways into
other site of the lung, trachea and larynx, through
lymphatic into lymph nodes or it may erode the wall
of blood vessels entering the circulation and lodging
the entire lungs or many other organs with the
formation of diffuse small foci localization known as
miliary tuberculosis.
• There may be pleural involvement in the form serous,
purulent or massive oblitrative fibrous pleuritis or
sometimes serous pleural effusion or frank
tubeculous empyema.

21. 2. Miliary tuberculosis (M.T):
The lymphohermatogenous spread may give rise
M.T confined to the lungs or involving other
organs and the distribution of the lesion
depends on the pathway of dissemination. The
favored sites outside the lungs are bone
marrow, liver, spleen and retina. The lesions vary
from 1mm to several and are distinct yellow-
white firm area of consolidation without visible
central necrosis and cavitations.
Histological features: it is formed by single or
multiple confluent tubercles with microscopic
central caseation.

23. 3. Tuberculous bronchopneumonia:
In the highly susceptible, highly sensitized
individual, the infection may spread rapidly
throughout large area of lung parenchyma and
produce a diffuse bronchopneumonia or lobar
exudative consolidation. This is onces
descriptively referred as to galloping
consumption.
Sometimes, such disease may not form well
developed tubercle but there are numerous
bacilli in exudates which simple to pose a
diagnosis of tuberculosis.