Tuberculosis

It is an infectious bacterial
disease that mainly affects lungs

Gram stain
NEUTRAL

Causative Organism
 MODE OF TRANSMISSION
It is transmitted through

Inhalation Ingestion Inoculation Transplacental route

 Inhalation
Inhalation of organisms present in:

(a) Cough Drops

(b) Dried Sputum

 Ingestion
Ingestion of organism leads
to development of
TONSILLAR or INTESTINAL Tuberculosis

This occurs by
*Self swallowing of infected sputum

Or

*Ingestion of bovine tubercle from

Milk of diseased cow

 Inoculation
Inoculation of organism into skin may rarely occur
from infected postmortem tissue

Transplacental Route
It results in development of congenital tuberculosis
in foetus from infected mother.

It is a rare mode of transmission

Spread of Tuberculosis
 Spread of Tuberculosis
Disease spreads in the body through following routes

1. Local Spread: by macrophages carrying bacilli into

surrounding tissue

2. Lymphatic Spread: The bacilli may pass into regional lymph

nodes resulting in regional tuberculosis lymphadenitis in
childhood infections
 3. Haematogenous spread:

occurs either as a result of tuberculous bacillaemia from

drainage of lymphatics into venous system or due to caseous
material escaping through ulcerated wall of vein.

4. By natural passages:

i) lung lesion into pleura

ii) Transbronchial spread into adjacent lung segment
iii) Swallowing of infected sputum
iv) Renal lesions into ureter

Pathogenesis
 Pathogenesis
Hypersensitivity and immunity play major role in development
of lesion in tuberculosis.

Tissue changes seen in tuberculosis are not the result of any

exotoxin or endotoxin but are instead the result of host
response to the organism which is by way of development of
delayed type hypersensitivity and immunity.
 Hypersensitivity and immunity are closely related and are
initiated through CD4+T sensitised against speci c antigen.

Sensitisation of CD4+ T cell

release

Lymphokines
induce

Increase in microbicidal activity

of macrophages

Tissue reaction to tubercle bacilli is different

in healthy animal not previously infected from an animal who
is previously infected

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 Primary Tuberculosis

Koch’s Phenomenon

Secondary Tuberculosis
 Koch’s Phenomenon
Experiment on guinea pig

1. In primary infection
Intradermal injection of tubercle bacilli

No visible reaction for 10-14 days

after a period of time
Nodules develop at the site of inoculation

Ulcerates

Heals poorly
 Regional lymph nodes develop tubercles
Delayed type hypersensitivity
Comparable to primary tuberculosis in children

2. In secondary infection
Previously infected animal

Injected with tubercle bacilli

1-2 days
Site of inoculation is indurated and dark, attaining a diameter
of about 1 cm

Skin lesion ulcerates

Heals quickly and regional lymph nodes are not affected

Evolution of
Tubercle
 Evolution of Tubercle
Tubercle bacilli injected IV into guinea pig

Lodged in pulmonary capillaries

Initial response of neutrophils

12 hrs
In ltration of macrophages

Kill bacteria Die away themselves Activated CD4+T cells

Increased cytokines(TNFCl and IL-1, IL-2 etc)

Increased proliferation of macrophages

1-2 days
Macrophages undergo structural changes:
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 Cytoplasm- pale and eosinophilic
Nuclei- elongated and vesicular
Are called epithelioid cells

Epithelioid cells aggregate

Granuloma

Some macrophages are unable to destroy tubercle bacilli, fuse together and form multi-nucleated
giant cells

Hard tubercle
Ground cluster of epithelia cells and a few giant cells, a zone of lymphocytes and plasma cells is
formed which is further surrounded by broblasts
10-14 days
Soft tubercle
(Hallmark of tuberculosis lesions)
-Centre of the cellular mass begins to undergo caseation necrosis, characterised by cheesy
appearance and highly lipid content
- Microscopically caseation necrosis is structureless, eosinophilic and granular material with
nuclear debris.

Restrict proliferation of tubercle bacilli

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 Types of Tuberculosis
- 2 main types are as follows:

A) 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

- Primary complex or ghon’s complex is the lesion produced in the tissue of portal entry
with foci in draining lymphatic vessels in lymph node

- The bacilli are either inhaled or ingested or both accordingly they infect different
organs

-If inhaled, it will infect tonsils, cer vical lymph nodes, lungs and hilar lymph nodes

- If ingested, it will infect intestine and mesenteric lymph nodes

 -Primary complex in lungs consist of 3 components

1. Pulmonary component

1-2 cm solitary area of tuberculous pneumonia located peripherally under a patch of

pleurisy
- more in sub pleural focus in the upper part of lower lobe

2. Lymphatic vessel component

Lymphatics draining lung lesion contain phagocytes containing bacilli and may
develop beaded, military tubercles along the path if hilar lymph nodes

3. Lymph node component

Affected lymph nodes are matted and show caseation necrosis
- nodal lesions are potential source of reinfection later

Microscopy
Lesions of primary tuberculosis have the following features
1. Tuberculosis granulomas with peripheral brosis
2. Extensive caseation necrosis in the centres of granulomas
3. Old lesions have brosis and calci cation
Small periphery focus is seen in the intestine with enlarged mesenteric lymph nodes
producing tubes mesentria

Fate of Primary Tuberculosis

* Heal by brosis and

* in time undergo calci cation

* Progressive primary tuberculosis

* Primary miliary tuberculosis

* Progressive secondary tuberculosis

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Secondary Tuberculosis
 B) Secondary Tuberculosis
- The infection of an individual who has been previously infected or sensitised is
called secondary or post primary or reinfection or chronic tuberculosis

- Infection may occur from

- Endogenous source such as reactivation of dormant primary complex
- Exogenous source such as fresh dose of reinfection by tubercle bacilli

 Site
Secondary tuberculosis occurs most commonly in lungs.
Other sites include lymph nodes, pharynx, larynx, small intestine and skin.

Secondary pulmonary tuberculosis is discussed below

*The lesions in secondary pulmonary tuberculosis usually begin as 1-2 cm
apical area of consolidation of lung.

*It occurs by lymphohaematogenous spread of infection from primary

complex to apex of infected lung where oxygen tension is high and
favourable for growth of aerobic tubercle bacilli.

*Patients with HIV infection previously exposed to tuberculous infection

have high incidence of reactivation of primary tuberculosis.

Microscopy
The appearance is of typical tuberculous granulomas with caseation necrosis
Fate of secondary pulmonary tuberculosis
Lesions may heal with brous scarring and calci cation
OR
Lesions may coalesce together and produce progressive secondary pulmonary
tuberculosis with following pulmonary and extra pulmonary involvements:

i) Fibrocaseous involvements
ii) Tuberculous caseous pneumonia
iii) Miliary tuberculosis
iv) Tuberculosis empyema

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 Fibrocaseous Tuberculosis
-The area of tuberculous pneumonia undergoes peripheral
healing and massive central caseation necrosis which may

Remain as a soft caseous

Either break into bronchus OR lesion without
from a cavity, developing
drainage into a bronchus
Cavitary or open
to produce
brocaseous tuberculosis Chronic brocaseous
FURTHER PRODUCES tuberculosis

Endobroncheal Endotracheal Laryngeal Intestinal

Tuberculosis Tuberculosis Tuberculosis Tuberculosis

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 Grossly, tuberculous cavity is

spherical with
thick brous wall, lined by yellowish,
caseous,necrotic material.

Fibrocaseous Tuberculosis

Microscopically, the wall and lumen

of cavity show eosinophilic, granular,
caseous material.
Widespread granulomas show
Langerhans’s giant cells and lymphocytes
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 Tuberculous Caseous Pneumonia

The caseous material, in

an individual with
hypersensitivity may spread to
rest of the lung producing pneumonia

Miliary Tuberculosis
This is lymphohaematogenous spread of infection to systemic organs
The spread may occur to systemic organs or isolated organ.
The spread is either by entry of infection into pulmonary vein or into pulmonary
artery. The sites include liver, spleen, kidney, brain, meninges, bone marrow etc

Tuberculosis Empyema
The caseating pulmonary lesions of tuberculosis maybe associated with pleurisy. The
pleural cavity when contains caseous material, it develops tuberculous empyema.

Miliary Tuberculosis

Gross appearance

Microscopic appearance
RECAP
 PYQs

1. Discuss primary and secondary tuberculosis

2. Write a short note on primary tuberculosis

3. Draw the labelled diagram of a tubercle

4. Morphology and fate of GHON complex in tuberculosis

5. Write a short note on primary complex in tuberculosis