2. Tuberculosis, one of the oldest diseases known to affect
humans, is caused by bacteria belonging to the
Mycobacterium tuberculosis complex.
The disease usually affects the lungs, although in up to
one-third of cases other organs are involved
If untreated, the disease may be fatal within 5 years in
more than half of cases
Transmission usually takes place through the airborne
spread of droplet nuclei produced by patients with
infectious pulmonary tuberculosis
3. M. tuberculosis is a rod-shaped, non-spore-forming, thin
aerobic bacterium measuring 0.5 m by 3 m.
Once stained, the bacilli cannot be decolorized by acid
alcohol, a characteristic justifying their classification as
acid-fast bacilli.
Other organisms showing acid fastness include ;
Nocardia and Rhodococcus, Legionella micdadei, and
the protozoa Isospora and Cryptosporidium.
4.
5. Pathogenesis of tuberculosis
From exposure to infection;
M. tuberculosis is most commonly transmitted from a
patient with infectious pulmonary tuberculosis to other
persons by droplet nuclei, which are aerosolized by
coughing, sneezing, or speaking.
The tiny droplets dry rapidly; the smallest (10 m in
diameter) may remain suspended in the air for several
hours and may gain direct access to the terminal air
passages when inhaled.
6. There may be as many as 3000 infectious nuclei
per cough.
Determinants of transmission of tuberculosis;
1. The probability of contact with a case of
tuberculosis,
2. the intimacy and duration of that contact,
3. the degree of infectiousness of the case
4. Crowding in poorly ventilated rooms is one of
the most important factors in the transmission of
tubercle bacilli, since it increases the intensity of
contact with a case
7. Patients who have cavitary pulmonary disease or
tuberculosis of the respiratory tract (endobronchial or
laryngeal tuberculosis produce sputa containing as many
as 105 AFB/mL.
Patients with sputum smear–negative/culture-positive
tuberculosis are less infectious,
and those with culture-negative pulmonary disease and
extrapulmonary tuberculosis are essentially noninfectious.
8. From infection to disease;
the risk of developing disease after being infected
depends largely on endogenous factors, such as
1. the individual’s innate susceptibility to disease
2. and level of function of cell-mediated immunity.
Clinical illness directly following infection is classified as
primary tuberculosis and is common among children up
to 4 years of age.
Dormant bacilli, however, may persist for years before
reactivating to produce secondary (or postprimary)
tuberculosis, which is often infectious.
9. Risk factor for active tuberculosis;
Recent infection (1 year) 12.9
Fibrotic lesions (spontaneously healed) 12-20
Comorbidity
HIV infection
Silicosis
Chronic renal failure / hemodialysis
Diabetes
Intravenous drug abuse
Immunosuppresant treatment
Gastrectomy
Jejunoileal bypass
Post transplantation period
100
30
20-25
2-4
10-30
10
2-5
30-60
20-70
Malnutrition and severe underweight 2
10. PATHOGENESIS AND IMMUNITY
the majority of inhaled bacilli are trapped in the upper
airways and expelled by ciliated mucosal cells, a fraction
(usually 10%) reach the alveoli.
There, nonspecifically activated alveolar macrophages
ingest the bacilli.
The balance between the bactericidal activity of the
macrophage and the number and virulence of the bacilli
determines the events following phagocytosis.
11. In the initial stage of host-bacterium interaction, either the
host’s macrophages contain bacillary multiplication by
producing proteolytic enzymes and cytokines or the
bacilli begin to multiply.
About 2 to 4 weeks after infection, two additional host
responses to M. tuberculosis develop:
1. a tissue-damaging response and
2. a macrophage- activating response.
12. The tissue-damaging response is the result of a
delayed-type hypersensitivity (DTH) reaction to
various bacillary antigens; it destroys nonactivated
macrophages that contain multiplying bacilli.
The macrophage-activating response is a cell-
mediated phenomenon resulting in the activation
of macrophages that are capable of killing and
digesting tubercle bacilli. Although both of these
responses can inhibit mycobacterial growth, it is
the balance between the two that determines the
form of tuberculosis that will develop
subsequently.
13. With the development of specific immunity and
the accumulation of large numbers of activated
macrophages at the site of the primary lesion,
granulomatous lesions (tubercles) are formed.
These lesions consist of lymphocytes and
activated macrophages, such as epithelioid cells
and giant cells.
14. Cell-mediated immunity is critical at this early stage. In
the majority of infected individuals, local macrophages
are activated when bacillary antigens processed by
macrophages stimulate T lymphocytes to release a variety
of lymphokines.
These activated cells aggregate around the lesion’s center
and effectively neutralize tubercle bacilli without causing
further tissue destruction.
In the central part of the lesion, the necrotic material
resembles soft cheese (caseous necrosis)— a phenomenon
that may also be observed in other conditions, such as
neoplasms.
15. Even when healing takes place, viable bacilli may remain
dormant within macrophages or in the necrotic material
for years or even throughout the patient’s lifetime.
These “healed” lesions in the lung parenchyma and hilar
lymph nodes may later undergo calcification.
In a minority of cases, the macrophage-activating
response is weak, and mycobacterial growth can be
inhibited only by intensified DTH reactions, which lead
to tissue destruction.
16. The lesion tends to enlarge further, and the surrounding
tissue is progressively damaged. At the center of the
lesion, the caseous material liquefies. Bronchial walls as
well as blood vessels are invaded and destroyed, and
cavities are formed.
The liquefied caseous material, containing large numbers
of bacilli, is drained through bronchi. Within the cavity,
tubercle bacilli multiply well and spread into the airways
and the environment through expectorated sputum.
In the early stages of infection, bacilli are usually
transported by macrophages to regional lymph nodes,
from which they disseminate widely to many organs and
tissues
17. Cell-mediated immunity confers partial protection
against M. tuberculosis,while humoral immunity
has no defined role in protection.
Clinical manifestations
Tuberculosis is classified as pulmonary or
extrapulmonary.
Before the recognition of HIV infection, 80% of
all cases of tuberculosis were limited to the lungs.
18. PULMONARY TUBERCULOSIS
Pulmonary tuberculosis can be categorized as primary or
postprimary (secondary).
PRIMARY DISEASE
Primary pulmonary tuberculosis results from an initial
infection with tubercle bacilli.
The lesion forming after infection is usually peripheral
and accompanied by hilar or paratracheal
lymphadenopathy, which may not be detectable on chest
radiography. In the majority of cases, the lesion heals
spontaneously and may later be evident as a small
calcified nodule (Ghon lesion).
19. In children and in persons with impaired immunity (e.g.,
those with malnutrition or HIV infection), primary
pulmonary tuberculosis may progress rapidly to clinical
illness.
The initial lesion increases in size and can evolve in
different ways.
Pleural effusion, a frequent finding, results from the
penetration of bacilli into the pleural space from an
adjacent subpleural focus.
In severe cases, the primary site rapidly enlarges, its
central portion undergoes necrosis, and acute cavitation
develops (progressive primary tuberculosis).
20. Tuberculosis in young children is almost invariably
accompanied by hilar or mediastinal
lymphadenopathy due to the spread of bacilli from
the lung parenchyma through lymphatic vessels.
Hematogenous dissemination, which is common
and is often asymptomatic, may result in the most
severe manifestations of primary M. tuberculosis
infection.
21. POST PRIMARY DISEASE
Also called adult-type, reactivation, or secondary
tuberculosis, postprimary disease results from
endogenous reactivation of latent infection and is usually
localized to the apical and posterior segments of the upper
lobes, where the high oxygen concentration favors
mycobacterial growth.
The extent of lung parenchymal involvement varies
greatly, from small infiltrates to extensive cavitary
disease.
22. With cavity formation, liquefied necrotic contents are
ultimately discharged into the airways, resulting in
satellite lesions within the lungs that may in turn
undergo cavitation.
Massive involvement of pulmonary segments or
lobes, with coalescence of lesions, produces
tuberculous pneumonia.
While up to one-third of untreated patients reportedly
succumb to severe pulmonary tuberculosis within a
few weeks or months after onset, others undergo a
process of spontaneous remission or proceed along a
chronic, progressively debilitating course
(“consumption”).
