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Chronic Inflammation

Dr. Tarek Atia

Chronic Granulomatous Inflammation (CGI)

Definition: a type of chronic inflammation defined
by the presence of granulomas which are small,
(0.5 to 2mm) collections of modified "epithelioid"
histiocytes/macrophages and (Langhan's) giant
cells (fused histiocytes), with a background of new

capillaries, fibroblasts, and new collagen, usually

surrounded by a rim of lymphocytes.

Granulomas occur in response to

various diseases
Foreign body
Tuberculosis (Tb)
Fungal (mycotic) infections

Two factors necessary for granuloma


Presence of indigestible organisms or

particles (Tb, mineral oil, etc)
Cell mediated immunity (T cells)

Giant cell (Langhan`s cells)

Typical tuberculous granuloma showing an area of

central necrosis, epithelioid cells, multiple Langhan`stype giant cells, and lymphocytes

Factors necessary for resolution

Removal of the offending agent
Regenerative ability if cells have been destroyed

Intact stromal framework

- Infection means tissue invasion by pathogenic organism.

- The result of infection depends on:-

- Dose and virulence of the organism

- Body resistance (immunity)
- If the defense mechanisms failed to localize the
infection, organisms or their toxins reach the circulation
and produces their specific manifestations.




1- Toxaemias
- Toxaemia means circulation of bacterial toxins in the
blood with production of clinical manifestations.

- It could be acute if a large doses of toxins reaches the

blood within a short time; e.g. pneumonia & cholera.
- Or could be chronic if a small doses of toxins reaches

the blood within a long time; e.g. TB

Clinical manifestations of toxaemia

- Affect the brain: fever, headache, body aches, rigors,

- Affect the kidney: tubular necrosis, acute renal failure.
- Affect the heart: toxic myocarditis.
- Affect the liver: fatty liver
- Toxic shock
- Peripheral neuritis

2- Bacteraemia
- It means circulation of bacteria, from a septic focus
(sinusitis, otitis media, tonsillitis, ..), in the blood with
production of clinical manifestations.

- Its effect depends on:- Body resistance

- Dose and virulence of the organisms

3- Septicemia
It means multiplication of bacteria and their

toxins in the blood with production of sever clinical

- The causes include:- Lowering of the body resistance
- Virulent pyogenic organisms e.g.
- Gonococci in meningitis
- Staph aureus in osteomyelitis

4- Pyaemia
- It means production of multiple small abscesses in
different organs due to circulation and impaction
of septic emboli started from a septic focus.
- According to the site of the original septic focus;
pyaemia can be classified into: Systemic or Portal


Tuberculosis (TB)
Communicable disease
It is a chronic granulomatous disease
Causative organism: Mycobacterium tuberculosis;
tubercle bacilli of two types (human and bovine),
Typically results in caseating (necrosis) granulomas

Route of infection
Respiratory tract: Inhalation of infected
droplets from patient with open TB.

Intestinal tract: Ingestion of infected milk

Skin by inoculation: (butchers).
Congenital by transplacental spread

Macrophages are the primary cells infected by M.
Early in infection bacilli replicate & are
essentially unchecked
later in infection T-helper response stimulates
macrophages to contain the proliferation of the

Once inside the macrophage, M. tuberculosis

replicates within the phagosome by blocking fusion

of the phagosome & lysosome


Types of Tb infection
Primary TB
- Nature: Infection for the 1st time

- Age:

Secondary TB
- Re-infection (2nd time)


- Hypersensitivity and immunity :

not developed

- Adult
- Well developed

- Tissue reaction: Proliferation

- Sites: Tonsil, lung, intestine

- Exudative
- Anywhere

- Lymph nodes: Always affected

- Not usually affected

Primary TB
In Non Immunized individuals (Children)
Primary Tuberculosis:

Self Limited disease

Ghon`s focus, Primary complex.

Primary Progressive TB
Miliary TB and TB Meningitis.

Common in Immuno-suppressed individuals

Sites of 1ry TB
- 1ry cervical complex: TB tonsillitis, TB lymphadenitis,
TB lymphangitis.

- 1ry pulmonary complex: Ghon`s focus, TB hilar

lymphadenitis, TB lymphangitis .

- 1ry intestinal complex: TB enteritis, TB lymphadenitis,

TB lymphangitis.

Ghon`s Focus
Small rounded about 1cm
focus, present anywhere in



peripheral and subpleural.

Central caseation and cold

abscess may occur.

Primary or Ghons Complex

Primary tuberculosis is the

pattern seen with initial

infection with tuberculosis
in children.
Reactivation, or secondary
tuberculosis, is more
typically seen in adults.

Secondary Tuberculosis:
Post Primary in immunized individuals.

Reactivation or Reinfection
Caseation, cavity - soft granuloma

Pulmonary or extra-pulmonary
Local or systemic spread / Miliary
Vein via left ventricle to whole body
Artery miliary spread within the lung

Tissue reaction to Tb bacilli

Cellular (proliferative) reaction: occurs in 1ry TB, and

leads to a tubercle (granuloma) formation , which

is microscopically formed of
- Epitheloid cells
- Caseation necrosis
- Giant cells
- Lymphocytes
- Fibroblasts

Cavitary Tuberculosis




coughed up cavity.
Cavitation is typical for large
Cavitation is more common
in the secondary reactivation
tuberculosis - upper lobes.

Fate of Tuberculosis
1- When the body resistant is good: healing occurs by
fibrosis, followed by calcification and ossification.
2- When the body resistant is low: spreading of the
infection :-Blood
- Direct along the tissue space
- Along the natural passages
- Along the serous cavities as pleura
- Lymphatic to the regional lymph nodes

Morphology of granuloma
1. Collection of chronic inflammatory cells.
2. Central Caseous necrosis.
3. Active macrophages - epithelioid cells.

4. Outer layer of lymphocytes, plasma cells & fibroblasts.

5. Langhans giant cells fused epithelioid cells.

Epitheloid cells in

Caseation necrosis

Typical Cavitating

TB Brain

TB intestine

Spinal TB - Potts Disease