Infection

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)

Syphilis

Fungal (mycotic) infections

Two factors necessary for granuloma formation

Presence of indigestible organisms or

particles (Tb, mineral oil, etc)

Cell mediated immunity (T cells)

Typical tuberculous granuloma showing an area of

central necrosis, epithelioid cells, multiple Langhan`s-

type giant cells, and lymphocytes

Giant cell (Langhan`s cells)

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.

InfectionInfection

Pathogenesis

ImmunityImmunity

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,

tachycardia.

- 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

manifestations:

- 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

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

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

Route of infection

Pathogenesis

Macrophages are the primary cells infected by M. tuberculosis.

◦ Early in infection bacilli replicate & are essentially unchecked

◦ later in infection T-helper response stimulates

macrophages to contain the proliferation of the

bacteria.

• Once inside the macrophage, M. tuberculosis

replicates within the phagosome by blocking fusion

of the phagosome & lysosome

Pathogenesis

Types of Tb infection

Primary TB

- Nature: Infection for the 1st time

- Age: Children

- Hypersensitivity and immunity :

not developed

- Tissue reaction: Proliferation

- Sites: Tonsil, lung, intestine

- Lymph nodes: Always affected

Secondary TB

- Re-infection (2nd time)

- Adult

- Well developed

- Exudative

- Anywhere

- 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

the lung, commonly

peripheral and subpleural.

• Central caseation and cold

abscess may occur.

Primary or Ghon’s 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

When necrotic tissue is

coughed up cavity.

Cavitation is typical for large

granulomas.

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 granuloma

Caseation necrosis

Typical Cavitating Granuloma

TB Brain

TB intestine

Spinal TB - Potts Disease