(Tuberculosis (TB

Dr: Mie Ali Ali Mohamed

 Tuberculosis
Epidemiology

 1.7 billion individuals are infected

worldwide, 8-10 million new cases develop
each year and 1.7 million deaths per year.

 TB is the leading cause of death worldwide

after HIV.

 Infection with HIV makes people susceptible

to rapidly progressive tuberculosis
 Tuberculosis
Epidemiology

 Tuberculosis flourishes wherever there is

poverty, crowding, and chronic
debilitating illness. In the United States,
tuberculosis is mainly a disease of the
elderly, the urban poor, and people with
AIDS

 Incidence increases with DM, Hodgkin’s

disease, renal failure, malnutrition,
chronic alcoholism and immune
suppression.
Tuberculosis
T.B bacilli are
Aerobic
Acid fast
Non motile

Do not
produce toxins
 Mycobacterium
Mode of infection
 Human type…by droplet
infection from an open, active
pulmonary disease.

 Oropharyngeal and intestinal

lesions are acquired by drinking raw
contaminated milk by bovine type of
bacilli.
 Pathogenesis of
tuberculosis
 Organism is phagocytosed by macrophage
which is not able to destroy virulent micro-
organism.

 In the early phase of primary tuberculosis,

(in the non immunized person), there's
uncontrolled proliferation of bacilli within
pulmonary alveolar macrophages with
resulting bacteremia and seeding of
multiple sites.
Pathogenesis of
tuberculosis
 Pathogenesis of
tuberculosis
 After 3 weeks of infection, cell mediated immunity
develops. Macrophages process mycobacterial antigen
and present it to unstimulated CD4+Tн0 cells.
 Under effect of IL-12 secreted by macrophages,
CD4+Tн0 cells mature into CD4+Tн1 cells which
secrete IFN-γ .
 IFN-γ activates macrophages to secrete a group of
mediators including:-
 Pathogenesis of
tuberculosis
1- TNF… causing recruitment of monocytes, their
activation, differentiation to epithelioid cells. It
also causes
a. Increased NO production which generate
free radicals able to destroy the microorganism.
b. Secretion of IL-8 which is chemotactic for
lymphocytes and monocytes.
 Pathogenesis of
tuberculosis

2- IFN-γ …. which helps in

a. Macrophage activation for more
phagocytosis, antigen presentation
and microbial killing.
b. Secretion of TGF- β which
stimulate fibroblastic proliferation
Pathogenesis of
tuberculosis
 Pathogenesis of
tuberculosis
 The development of immunity
(protection) to TB bacilli is
accompanied by hypersensitivity
(tissue destruction).
 Re-exposure to TB bacilli in a
previously sensitized host results in
rapid mobilization of defensive
mechanism and also increased tissue
necrosis.
 Pathogenesis of
tuberculosis
TNF
1- Increased NO production
which generate free radicals.
2- Secretion of IL-8 which is
chemotactic for lymphocytes
and monocytes
IFN-γ
1- Macrophage activation
2- Secretion of TGF- β which
stimulate fibroblastic
proliferation
 Pathogenesis of
tuberculosis

The reaction ends by the formation of

epithelioid granulomas with giant cells ,
central caseation and peripheral fibrosis.
Types of tuberculous
reaction
 Primary Tuberculosis

Sites
1- Lungs
2- Intestine
3- Tonsils
4- Skin
5- Nose
 Primary pulmonary
complex
 It is the form of disease
that develops in a
previously unexposed,
and therefore
unsensitized persons.
 It is more common in
children.
 Source of infection is
exogenous.
 About 5% of infected
persons develop
significant disease.
 Primary pulmonary
complex
Consists of:-

1-Gohn’s focus

2- Lymphangitis

3- Hilar lymphadenitis
Gohn’s Focus
Primary pulmonary
complex
Ghon’s focus:-
-1-1.5 cm in diameter,
grey-white.
- Found in the lower
part of upper lobe or
upper part of lower
lobe usually close to
the pleura.
- Central part
undergoes caseation.
 Primary pulmonary
complex

M/E:
-Caseating and noncaseating granulomas formed of
epithelioid cells,Langhan’s giant cells, Lymphocytes
and peripheral fibroblasts.
- Hilar lymph nodes show the same granulomatous
reaction
 Fate of the primary
complex
1- Primary infection induces both
immunity and hypersensitivity.

2- Healing by fibrous tissue ,

dystrophic calcification. These foci
can harbor viable organism for
years
(latent tuberculosis) to be
activated later if the immunity of
the patient is lowered.
 Fate of the primary
complex
3- Uncommonly, the disease may pass
without interruption into progressive
primary tuberculosis.
-This occurs in immune suppressed
patients (HIV infected, malnourished
children and elderly patients).
 Fate of the primary
complex
4- Spread
a. Local……..pleura & adjacent lung
tissue.
b. Blood……more in primary TB it
leads to miliary tuberculosis
c. Lymphatic ++leading to
tuberculous lymphadenitis.
d. Natural passages....less common
than secondary…it leads to the
development of tuberculous
bronchopneumonia and pneumonia.
 Fate of the primary complex ( blood
(Spread

 If an enlarging caseating lymph node

erodes a vessel wall, TB bacilli are carried
in the blood stream to many parts of the
body including the remainder of the lung
causing miliary tuberculosis.
 If drainage occur through the pulmonary
vein there is systemic dissemination of the
organism (kidneys, liver, spleen).
 If drainage occur through pulmonary
artery, dissemination occurs within the
lungs
 Miliary T.B
In miliary TB, the affected
organ will be studied with
multiple, uniform, tiny
yellow-white dots in
relation to small blood
vessels. The dots are
not surrounded by
hyperemic zones like
pyemic abscesses.
M/E:-
Early tubercles with giant
cells and little caseation.
 TB bronchopneumonia
 Bronchial spread of organisms
produce tuberculous
bronchopneumonia.

 In primary tuberculosis, if an
infected lymph node erodes into
a bronchus, tuberculous caseous
material containing living TB
bacilli passes down bronchi and
bronchioles under influence of
gravity to lower lung tissue
causing confluent caseating
granulomatous lesions. This
lesion is usually rapidly fatal and
is called (galloping consumption)
 Secondary tuberculosis
 In secondary TB the organism may be
acquired exogenously or from reactivation
of a healed primary complex.
 It usually occurs in adults.
 Hypersensitivity reaction leads to excessive
tissue destruction and extensive caseation.
 No nodal affection as the organism is
destroyed in the necrotic tissue.
 Secondary pulmonary tuberculosis

 An apical lesion (Assmann

focus) begins as a small
caseating tuberculous
granuloma.
 In most cases, destruction of
the lung leads to cavitations.
 There’s little involvement of
lymph nodes as spread of the
organism to regional nodes is
prevented by massive tissue-
based hypersensitivity
response.
 Secondary pulmonary tuberculosis

M/E:-
As in Ghon’s focus,
there’s a central
area of caseation
that is surrounded
by granulomatous
inflammatory
reaction.
 Fate of Secondary pulmonary
tuberculosis

The outcome of the infection depends on

the balance between dose and virulence
of the organism with the body immunity.
 Fate of Secondary pulmonary tuberculosis

1- With good immunity, healing

of the apical lesion occurs
and a dense fibrous capsule
surrounds a central area of
caseation (Fibrocaseous
tuberculosis).
- Calcification often
supervenes, and a (latent
tuberculosis) develops
which can be reactivated if
the patient’s immunity is
lowered.
 Fate of Secondary pulmonary tuberculosis
((bronchial spread

2- In adults with poor immune response,

secondary TB progresses locally with
massive tissue destruction and poor fibrosis.
The release of TB bacilli into the main
bronchi leads to:-

a. Open tuberculous lesion in which TB bacilli

are coughed into the atmosphere and
droplet infection can occur to other people,
or infected sputum is swallowed leading to
TB laryngitis or enteritis.
 Tuberculous
bronchopneumonia

b. TB bronchopneumonia in which spread of infection occurs to the lower lobes

of the lungs.
Apical lesion + TB bronchopneumonia

Yellowish patches
represent
inflammation of
bronchioles and
surrounding lung
tissue
(bronchopneum
onia(
 Apical lesion + TB
pneumonia
Spread of infection
from the apical
lesion to the
surrounding lung
parenchyma leads
to tuberculous
pneumonia.
 Hemorrhage into a T.B
cavity
Erosion of blood
vessels by
tuberculous reaction
can lead to
hemorrhage into the
cavity with coughing
of blood
(hemoptysis)
Fate of Secondary pulmonary tuberculosis
((Blood spread

3- In adults with poor immune response

blood spread of the organism can occur,
the final outcome of blood spread
depends upon dose and virulence of the
organism and body immunity….

*Low dose organism with low virulence +

good body immunity……most of the
organism will die.
Fate of Secondary pulmonary tuberculosis
((Blood spread

Moderate dose organism with

Moderate virulence + Moderate body
immunity….. The organism usually
settle in one organ leading to
(isolated organ tuberculosis).
Fate of Secondary pulmonary tuberculosis
((Blood spread

Organs most commonly affected are

- Kidney
-Suprarenal gland
- Fallopian tube
- Epididymis.
- Brain and meninges.
- Bone and joints.
 Fate of Secondary pulmonary tuberculosis
((Blood spread

High dose organism with

high virulence + low
body
immunity…..Spread of
the organism to all
body organs leading to
miliary tuberculosis
 Miliary tuberculosis lung
Grossly ..
Affected organ shows a
large number of

- Small
-Uniform
- Grayish – yellow dots
- Near small blood vessels.
- Not surrounded by a
zone of hyperemia.
Milliary tuberculosis
spleen
 Miliary Tuberculosis
M/E…..
The affected organ
shows large number of

-Small uniform
epithelioid granulomas
with giant cell
but with little
caseation and little or
no surrounding
fibrosis.
Tuberculo
ma

 It is a localized mass of caseating tuberculous reaction

surrounded by fibrous tissue.
 It may reach a large size (to be mistaken for a tumor)
 It can occur at any organ (lung, kidney, brain…)
Complications of pulmonary tuberculosis

1- Local tissue destruction….

- Blood vessels…hemorrhage & hemoptysis
- Bronchi..open to the pleura leading to
pneumothorax and pyopneumothorax.
- Reactive systemic amyloidosis.
2- Pulmonary fibrosis…pulmonary
hypertension ..right sided heart failure (cor
pulmonale).
3- Spread…..*Local to the pleura (pleurisy)
*Bronchial…TB pneumonia and
bronchopneumonia
*Blood…..isolated organ TB or miliary TB
Thank you