5- infection (tb)
DESCRIPTION
InfectionTRANSCRIPT
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