What is Chronic Inflammation:
Inflmmation of prolonged duration in which inflmmation, tissuue injury and attempts at repair coexist, in varying combinations.
- Chronic Suppurative on acute:
- Chronic granulomatus: (Initiates without an acute phase)
Suppurative in type:
- Inadequate or delayed drain leads to thick fibrous wall formation.
- The residual bacteria get reactivated
- Pus formation.
- Presence of foreign material or indigestible dead tissue.
Eg: Osteomyelitis, damaged Collagen
Follow acute inflammation
Persistence of the stimulus
Disturbance to the healing process
Repeated bouts of acute inflammation and healing in between.
Low grade persistent infection.
- Microorganisms where body can mount limited immune reactions
- Impaired Sequelae of an acute inflammation
- Foreign bodies
- body defense
- Immune reactions
Chronic inflammation without an acute phase
Infection: TB, Leprosy, Syphilis
Immunological: Rheumatoid arthritis Ulcerative colitis Crohn’s disease
Poor blood supply (leg ulcer)
Chronic inflammatory lesions
May vary histologically according to causative agent
However there is a set of morphological features in common.
- Infiltration by mononuclear cells
- plasma cells
- Proliferation of blood vessels/fibrosis (angiogenesis)
- Tissue destruction (induce by inflammatory cells)
Mononuclear phagocytic system
Macrophages (at extra vascular tissue)
Tissue macrophages (Scattered in connective tissue or concentrated in organs)
Eg: Kupffer cells in Liver
Sinus histiocytes in lymph nodes
Alveolar macrophages in lung
Osteoclasts in bones
Morphological transformation (macrophages and giant cells)
Secretion of biologically active products
Cells types present
- Mast cells
Existence of CI, AI and repair
- Macrophages persist at the site (Due to the influence of chemical mediators)
- Destruction of invading microorganisms /normal tissues
- Secretion of chemical mediators by macrophages
- Functions of them,
- Proliferation of fibroblasts, Laying down of collagen
- Angiogenesis, Activation of lympho macrophages
- Dead and dieing leukocytes/necrotic tissues helps in developing acute inflammation
Granulomas /Granulomatus infection
- Chronic inflammatory lesion in the form of mass.
- Collection of macrophages or modified macrophages (epitheliod / giant cells)
- Granulomas /Granulomatus infection
- A granuloma is a focal area of granulomatus inflammation.
- Consist of macrophage aggregation
- Epithelial cell transformation
- Collar of lymphocytes
- Appearance giant cells and of fibrosis can see with the time
- Cat scratch disease
- Mycotic infections
Two types of granulomas: Base on pathogenesis
Foreign body type:
Form around foreign bodies
Immune type: When the foreign practical are capable of induce cell mediate immune responses
(but not always granulomas will develop)
Granulomas is a result of chronic inflammatory reaction containing a collection of cells of monocytic series arrange in a compact mass.
Giant cells: Langhans giant cells
Foreign body type giant cells
Accumulation of macrophages
Under the influence of chemotaxis
C5a, fibrinopeptides, cationic proteins
products of collagen brake down
By mitotic division
Immobilization and prolong survival (if the irritants are low virulent )
Chronic disease common worldwide.
Causes a characteristic granulomatous inflammation
Inability of the neutrophils to kill the micro organisms due to lipoprotein coating.
Bovis (Tonsils, Intestine)
- Droplet from patients (weeks or months)
- However need sustain contact than casual contact.
MT has no Endotoxins
Development of immune response against outer coat of the organism.
2 to 4 weeks after infection : + Tuberculin test
PPD (purified protein derivative)
(Culture in which TB is grown)
Induration More that 5.mm within 48 hours.
Positivity indicates infection but not the disease.
Occurs in individuals who have never previously been infected with M. tuberculosis (childhood infection if TB is common, adult life if uncommon)
Usually caused by inhalation of the organisms or rarely by ingestion of the organism.
Tonsils neck nodes
In respiratory system, inhalation of the organisms cause a subpleural lesion usually in the lower part of the upper lobe or upper part of the lower lobe. This is called Ghon focus.
Location is in these sites is because bacterium is a strict aerobe and prefers these well oxygenated regions
When the tissue is invaded by the mycobacteria there is no hypersensitivity reaction. Instead there is acute, non specific inflammatory response with predominant neutrophils.
This is followed by macrophages which ingest the bacilli and present Ags to to T lymphocytes leading to proliferation of a clone of T cells .
The emergence of specific hypersensitivity lead to release of lymphokines,that attract more macrophages.
These accumulate to form the characteristic granuloma.
1 to 2 cm
Location –Beneath pleura- mid zone of the lung
Tubercle bacilli, either free or contained in macrophages, may drain to the regional lymph nodes and set up granulomatous inflammation, causing massive lymph node enlargement.
The combination of the Ghon focus, draining lymphatics and the regional lymph nodes is called the primary complex.
Calcification of the lymph nodes
Sequelae of primary complex
Healing with small fibrous scar replacing caseous necrosis. Lesion will be walled off.
Reactivation of infection later when host defences become lowered.
Enlarged caseous nodes can obstruct bronchi, leading to collapse, retention of secretion and inflammatory consolidation
Caseous node erodes into a bronchi with satellite lesions in lungs (TB bronchopneumonia).
Eroding into a pulmonary vein causing generalised milliary TB.
Erosion into pulmonary artery leads to miliary TB of lungs
Opening of the caseous node to a bronchus.
Air bone infection
(Multiple pneumonic patches arrangeed in and around terminal bronchi)
The lesions spread rapidly and accumulate macrophages and lymphocytes followed by necrosis
Necrotic patches get enlarged and discharged which will lead to dissemination and cavitations. (no fibrous walls)
TB bronchopneumonia can happen after both 1ry and 2ry TB.
Rapidly spreading tuberculous bronchopneumonia: debilitated by intercurrent disease, diabetes, malnutrition etc.
Acute miliary tuberculosis of the lungs due to blood stream spread to lungs. Grey tubercles visible to naked eye 3mm in diameter. More numerous and larger in upper lobes than lower lobes. Microscopically these are ill formed and often giant cells are absent. Usually these lesions do not cavitate
Effects on the other organs of the body
Miliary tuberculosis due to systemic spread to kineys, spleen, brain, liver etc.
Tuberculous ulcers in the intestine due swallowed sputum.
Tuberculosis of larynx due to direct spread from sputum.
Common with 1ry TB
Due to involvement of veins
Multiple scatted tubercles
Not well developed/uniform in size
Some times without giant cells (necrosis)
Secondary Tuberculosis (Post primary)
Infection may me exogenous or endogenous
After active primary infection
Reactivation asymptomatic primary lesions:
Intercurrent lung infection,
Exogenous: caused by inhaled organisms
During primary tuberculosis or during BCG immunisation, the patient develops cell mediated immunity to antigens of tubercle bacillus.
This is demonstrated by skin test (Mantoux) test
Immunity is associated with increased resistance to subsequent infection.
Re infected lesions:
Apex of the lungs
Endogenous infections (swallowing sputum)
Metastatic lesions are similar to re-infected
Large in size (spread locally) no lymph node involvement
Caseous material discharge gradually leaving a small cavity.
Cavities can become very large with overgrowth of fibrous tissue.
Cavity walls are irregular with raised bands representing obliterated blood vessels.
The surface is lined by caseous material or by pus and debris mixed with blood.
If the disease is inactive the wall becomes very smooth
In early cases the lesions are often in the apices of the lungs
In advanced cases there may be more than one cavitatory lesion.
All the lesions are distributed in the upper part of the lungs
Caseation may involve the wall of a bronchus leading to obstruction of the lumen.
Sequelae of tuberculous cavities
Due to fibrosis lung tissue shrinks causing bronchiectasis (upper lobe bronchiectasis)
Blood vessels can become weaken and rupture leading to haemoptysis
Aneurysm formation- called Rasmoussen’s aneurism leading to fatal haemorhage.
Fungal infections can be localized in these cavities.
Seen in non immune people.
Usually childhood cases
Subpleural mid zone
Lymph nodes are always involved
Seen in immune people
Lymph nodes are not always involvecd