Chronic inflammation

What is Chronic Inflammation:

Inflmmation of prolonged duration in which inflmmation, tissuue injury and attempts at repair coexist, in varying combinations.

1. Chronic Suppurative on acute: 
2. Chronic granulomatus: (Initiates without an acute phase)

Suppurative in type:

Abscesses

• 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.    

Causes

• 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.  

Histologically

• 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)

Monocytes

Migration

Morphological transformation (macrophages and giant cells)

Activation

Secretion of biologically active products

Cells types present

• Macrophages            Ÿ 
• Eosenophils
• Mast cells                 
• ŸLymphocytes

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
• ŸDead 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 

    

Eg: 

• 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)

Definition

Granulomas is a result of chronic inflammatory reaction containing a collection of cells of monocytic series arrange in a compact mass.

Cells

Macrophages

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 )

Tuberculosis:

Chronic disease common worldwide.

Causes a characteristic granulomatous inflammation

Inability of the neutrophils to kill the micro organisms due to lipoprotein coating.

Mycobacterium tuberculosis.

Hominis (lungs)                                                

Bovis (Tonsils, Intestine) 

Spread

• Droplet from patients (weeks or months)
• Conjunctiva
• Punctures
• However need sustain contact than casual contact.

Tissue damage 

MT has no Endotoxins

Exotoxins 

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 5.mm 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.

Calcification

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)

Pneumothorax

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.

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:

Malnutrition,

Severe illness,

Intercurrent lung infection,

Systemic immunosuppression

Exogenous: caused by inhaled organisms

Immunity

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

Lesions

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.

Tuberculosis                 
Primary

Seen in non immune people.

Usually childhood cases

Subpleural mid zone

Lymph nodes are always involved

Seen in immune people

Secondary

Often adults

Lung apices

Lymph nodes are not always involvecd