Lecture 4

Chronic Inflammation

Dr. Mehzabin Ahmed

24 September 2008
Chronic Inflammation, tissue destruction and fibrosis

Introduction

 When a damaging stimulus persists, complete healing

cannot occur, and chronic inflammation results

 In chronic inflammation the tissue damage continues

along with attempts to repair

Types:
5) Chronic non specific inflammation
6) Chronic granulomatous inflammation
 Causes of chronic inflammation
 Persistence of infections by organisms of low toxicity

Cause an delayed type of immune reaction

Results in a granulomatous inflammation

Bacteria like M. tuberculosis, T. pallidum; viruses;
fungi; parasites etc
 Prolonged exposure to potentially toxic substances
 Exogenous- silica particles - silicosis
 Endogenous- toxic plasma lipid components-
atherosclerosis
 Autoimmunity

reaction against the body’s own tissues

Results in chronic tissue damage and inflammation

Rheumatoid arthritis, systemic lupus erythematosus
Features of chronic inflammation

 Infiltration with mononuclear cells- lymphocytes, plasma cells

and macrophages

 Tissue destruction- seen as areas of necrosis in the affected

tissues- caused by the persisting microorganisms and the
inflammatory cells

 Attempt at healing- seen as areas of fibrosis (connective tissue

replacement of the damaged tissues) accompanied and helped
by angiogenesis (the proliferation of new vessels)
 Mononuclear infiltrate associated with immune response
 Immune mechanisms dominate the cellular response in
chronic inflammation
 The macrophage is the main effector cell in chronic
inflammation
 Lymphocytes and plasma cells are also present in chronic
inflammatory reactions

macrophage
lymphocyte

Plasma cells
Chronic peptic ulcer is an example of chronic
inflammation where tissue damage due to
acid-peptic digestion and tissue repair are
going on at the same time
Peptic ulcer

fibrosis
Chronic Inflammation, tissue destruction and fibrosis
Peptic ulcer
Granulomatous inflammation:
 It is a distinct type of chronic inflammation.
 There is a focal collection of activated macrophages called
epithelioid cells.
 Granuloma: it is the focus of chronic inflammation
consisting of
 Epithelioid cells
 Lymphocytes
 Plasma cells and
 Giant cells- formed by fusion of epithelioid cells
Types of granulomas
 Based on mechanism:
 Immune granuloma - there is a cell mediated
immune response against an insoluble particle like
microbes
 Eg: tuberculosis, Sarcoidosis, Fungal infections

Foreign body granuloma- they result form a
relatively inert substances- the foreign body may be
seen in the center of the granuloma
 Eg: talc, sutures
 Based on morphology:

Caseating granulomas: there are areas of caseous
necrosis (seen as cheesy white areas) in the affected
tissues. Seen in cases of tuberculosis.

Noncaseating granulomas- there is no central
caseation. It is seen in sarcoidosis, fungal infection.
 Granuloma formation is seen in some
chronic diseases
 In chronic inflammations macrophages
form groups called granulomas
 Granulomatous inflammation is seen
 when an organism is of low

pathogenicity but excites an immune

response e.g.
 Mycobacterium tuberculosis

 Mycobacterium leprae

 Fungus

 Virus

 Parasite
Granuloma
 Langhans Giant Cell
Granuloma

Lymphocytic Rim
crosis
s   Ne
Ca seou

Epithelioid Macrophage
Granulomatous inflammation

lymphocytes

Granuloma made up of macrophages

Tuberculosis is an example of granulomatous inflammation

 A granuloma in TB is called a
tubercle
 A tubercle is composed of
activated macrophages with
surrounding lymphocytes and
fibroblasts
 In TB the granulomas undergo
caseation necrosis and heal by
fibrosis when the immunity is
good
Caseating granulomas are seen commonly in TB

epithelioid cells lymphocyte

giant
cells

Area of caseation
necrosis
 Granulomatous inflammation can be a tissue response to some
foreign materials

 Granulomas form when a non-living material is deposited in

the tissue and cannot be degraded easily

e.g. urate crystals in gout, inhaled organic dust
 Foreign body giant cells are formed by the fusion of
macrophages around the material
 Sarcoidosis is a granulomatous disease of unknown cause in
which the granulomas do not show caseation and heal by
fibrosis
Giant cells form by fusion of macrophages

Langhan giant cell Foreign body giant cell

 Non caseating granulomas

Noncaseating granuloma in
Granuloma healing by fibrosis Sarcoidosis
The outcome of tubercle formation depends on the adequacy
of the host immune response

 In primary TB the initial lung

lesion (Ghon focus) remains
small but the infection spreads
to the hilar lymph nodes
(primary complex)
Primary TB

 The primary complex will heal in most cases with

development of immunity to TB
 Rarely the primary complex will progress in patients with
poor natural immunity
 Bronchial spread of organisms produces tuberculous
pneumonia
 Blood stream spread of organisms produces miliary TB
Miliary TB

Pulmonary dissemination
 Miliary tuberculosis, Spleen

Slide 16.31
Secondary TB

 In adults secondary TB heals by fibrosis around the

caseating granulomas
 In adults with poor immune response secondary TB
progresses locally and spread to other sites
 Blood stream spread of the organism can lead to spread to
other organs
 Tuberculous lesions may become reactivated long after
healing
 Secondary tuberculosis

 In secondary TB initial tuberculous infection is at the apex of the

upper lobe of a lung with little lymph node involvement
Spinal TB - Potts Disease
Outcome of infection in TB