Chronic inflammation

What is Chronic Inflammation

Inflammation of prolonged duration in which inflmmation, tissuue injury and attempts at repair coexist, in varying combinations.
Chronic inflammation
  1. Chronic Suppurative on acute: 
  2. 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

Chronic inflammation

Follow acute inflammation
Persistence of the stimulus
Disturbance to the healing process
ŸRepeated 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
  • Macrophages
  • lymphocytes
  • plasma cells
  • Proliferation of blood vessels/fibrosis (angiogenesis)
  • Fibrosis
  • Tissue destruction (induce by inflammatory cells)  

Mononuclear phagocytic system

Blood monocyte:
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
Microglia (CNS)
Morphological transformation (macrophages and giant cells)
Secretion of biologically active products

Cells types present

  • Macrophages 
  • Eosenophils
  • Mast cells                 
  • Lymphocytes

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 
  • TB
  • Sarcoidosis
  • Cat scratch disease
  • Leprosy
  • Syphilis
  • 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.


Epithelioid cells
Giant cells: Langhans giant cells
Foreign body type giant cells  
Accumulation of macrophages under the influence of chemotaxis : C5a, fibrinopeptides, cationic proteins
Lymphokines :
PDGF, TGF(beta)
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.
Chronic inflammation
Mycobacterium tuberculosis.
Hominis (lungs)                                                
Bovis (Tonsils, Intestine) 
Chronic inflammation
  • Droplet from patients (weeks or months)
  • Conjunctiva
  • Punctures
  • However need sustain contact than casual contact.

Tissue damage 

MT has no Endotoxins
Histiolitic enzymes
Development of immune response against outer coat of the organism.

Tuberculin test

2 to 4 weeks after infection : + Tuberculin test
PPD (purified protein derivative)
(Culture in which TB is grown)
Induration More that within 48 hours.
Positivity indicates infection but not the disease.
Primary Tuberculosis
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.
Primary infection
Lungs             Hilum
Tonsils           neck nodes
Intestine         mesentery
Primary Tuberculosis
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

Ghon’s focus

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.
Ghon focus
Usually single
1 to 2 cm
Location –Beneath pleura- mid zone of the lung 

Microscopic appearance

Primary complex
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.
plural effusion
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

TB bronchopneumonia

Opening of the caseous node to a bronchus.
Air bone infection
TB bronchopneumonia
(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.
Secondary amyloidosis.
Chronic inflammation

Miliary TB

Common with 1ry TB
Due to involvement of veins
Multiple scatted tubercles
Not well developed/uniform in size
1-2 mm
Some times without giant cells (necrosis)
Secondary  Tuberculosis (Post primary)
Infection may me exogenous or endogenous
After active primary infection
Reactivation asymptomatic primary lesions:
Severe illness,
Intercurrent lung infection,
Systemic immunosuppression
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

Cavity formation

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

Local effects
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
Often adults
Lung apices
Lymph nodes are not always involved