Definition: Prolonged Inflammatory Process (Weeks or Months) Where An

CHRONIC INFLAMMATION
Definition: prolonged inflammatory process (weeks or months) where an

active inflammation, tissue destruction and attempts at repair are proceeding
simultaneously.
 Causes of chronic inflammation:
1. Persistent infections
 Certain microorganisms associated with intracellular infection such as

tuberculosis, leprosy, certain fungi etc characteristically cause chronic
inflammation.
2. Prolonged exposure to nondegradable but partially toxic substances! :
 endogenous ( lipid components ) which result in atherosclerosis

,exogenous substances such as( silica, asbestos).
3.Immune mediated inflammatory disease:
 chronic inflammation may occur by excessive and inappropriate

activation of the immune system (hypersensitivity diseases).
 In certain conditions immune reactions may develop against the

affected person’s own tissues(Autoimmune diseases) such as
rheumatoid arthritis are chronic inflammations from the onset .
1
 GENERAL FEATURES OF CHRONIC INFLAMMATION:
1. MONONUCLEAR CELL INFILTRATION:

Chronic inflammatory lesions are infiltrated by mononuclear
inflammatory cells like phagocytes
Phagocytes are represented by circulating monocytes, tissue

macrophages, epithelioid cells and sometimes, multinucleated giant cells.
The macrophages comprise the most important cells in chronic
inflammation.
The blood monocytes on reaching the extravascular space transform into

tissue macrophages.
Besides the role of macrophages in phagocytosis, they may get activated

in response to stimuli such as cytokines (lymphokines) andbacterial
endotoxins.
On activation, macrophages release several biologically active

substances e.g. proteases, oxygen-derived reactive metabolites and
cytokines, these products cause tissue destruction
In addition Macrophages initiate the process of tissue repair and are

involved in scar formation and fibrosis
Other chronic inflammatory cells include lymphocytes, plasma cells,

eosinophils and mast cells.
2
2. TISSUE DESTRUCTION OR NECROSIS. Tissue destruction and
necrosis are central features of most forms of chronic inflammatory lesions.
This is caused by
activated macrophages which release a variety of biologically active

substances e.g. protease, elastase, collagenase, lipase, reactive oxygen
radicals, cytokines
3. PROLIFERATIVE CHANGES. As a result of necrosis, proliferation of

small blood vessels and fibroblasts is stimulated resulting in formation of
inflammatory granulation tissue. Eventually, healing by fibrosis and
collagen laying takes place.
3
 the overall differentiation points between acute and chronic
inflammations include:
Acute Inflammation Chronic Inflammation
Vascular changes Vasodilatation & increased Minimal

permeability
Cell Monocytes/Macrophages
Neutrophils, Tissue
Populations Plasma cells, Fibroblasts
macrophages
Time course Insidious onset, weeks to years

Acute onset, minutes to days
Outcome Resolution, Tissue destruction,

Resolution, Abscess
fibrosis
formation, Chronic
inflammation
4
Classification of chronic inflammation:
Chronic inflammation can be classified into the following two types based
on histologic features:
1) Nonspecific chronic inflammation: This involves a diffuse

accumulation of macrophages and lymphocytes, plasma cells at site of
injury E.g. Chronic cholecystitis.
2) Specific inflammation (granulomatous inflammation):
 Definition: Granulomatous inflammation is characterized by the presence

of granuloma.
 A granuloma is a microscopic aggregate of epithelioid cells. Epithelioid cell
(is an activated macrophage, with a modified epithelial cell-like appearance
(hence thename epithelioid). The epitheloid cells can fuse with each other &
form multinucleated giant cells. So, even though, a granuloma is basically a
collection of epithelioid cells, it also usually contains multinucleated giant
cell & is usually surrounded by a cuff of lymphocytes and occasional plasma
cells., may surrounded by fibrosis.
There are two types of giant cells:
a. Foreign body-type giant cells :which have irregularly scattered nuclei in

presence of indigestible materials.
b. Langhans giant cells: in which the nuclei are arranged peripherally in a

horse –shoe pattern which is seen typically in tuberculosis.
Giant cells are formed by fusion of macrophages
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 Causes of granulomatous inflammation:
Major causes of granulomatus inflammation include:

a) Bacterial: Tuberculosis, Leprosy, Syphilis.
b) Fungal: Histoplasmosis.
c) Helminthic: Schistosomiasis
d) Protozoal: Leishmaniasis, Toxoplasmosis
E)Immunologic: Crohn disease
F) forign body granuloma: e.g., suture or splinter
g) Idiopathic: sarcoidosis
 The pathogenesis of granuloma:
1. Engulfment by macrophages: Macrophages and monocytes engulf the

antigen and try to destroy it. But since the antigen is poorly degradable,
these cells fail to digest and degrade the antigen, and instead undergo
morphologic changes to epithelioid cells.
2. CD4+ T cells. Macrophages, being antigen-presenting cells, having failed

to deal with the antigen, present it to CD4+ T lymphocytes. These
lymphocytes get activated and elaborate lymphokines (IL-1, IL-2,
interferon-, TNF-).
3. Cytokines. Various cytokines formed by activated CD4+ T cells and also

by activated macrophages perform the following roles:
i) IL-1 and IL-2: stimulate proliferation of more T cells.
ii)Interferon : activates macrophages.
iii) TNF- : promotes fibroblast proliferation
6
iv) Growth factors (transforming growth factor-,, plateletderived growth
factor) elaborated by activated macrophages stimulate fibroblast growth.

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CHRONIC INFLAMMATION

Definition: prolonged inflammatory process (weeks or months) where an

 Causes of chronic inflammation:

 Certain microorganisms associated with intracellular infection such as

2. Prolonged exposure to nondegradable but partially toxic substances! :

 endogenous ( lipid components ) which result in atherosclerosis

3.Immune mediated inflammatory disease:

 chronic inflammation may occur by excessive and inappropriate

 In certain conditions immune reactions may develop against the

1. MONONUCLEAR CELL INFILTRATION:

Phagocytes are represented by circulating monocytes, tissue

The blood monocytes on reaching the extravascular space transform into

Besides the role of macrophages in phagocytosis, they may get activated

On activation, macrophages release several biologically active

In addition Macrophages initiate the process of tissue repair and are

Other chronic inflammatory cells include lymphocytes, plasma cells,

activated macrophages which release a variety of biologically active

3. PROLIFERATIVE CHANGES. As a result of necrosis, proliferation of

Acute Inflammation Chronic Inflammation

Vascular changes Vasodilatation & increased Minimal

Time course Insidious onset, weeks to years

Outcome Resolution, Tissue destruction,

1) Nonspecific chronic inflammation: This involves a diffuse

2) Specific inflammation (granulomatous inflammation):

 Definition: Granulomatous inflammation is characterized by the presence

There are two types of giant cells:

a. Foreign body-type giant cells :which have irregularly scattered nuclei in

b. Langhans giant cells: in which the nuclei are arranged peripherally in a

Giant cells are formed by fusion of macrophages

Major causes of granulomatus inflammation include:

d) Protozoal: Leishmaniasis, Toxoplasmosis

E)Immunologic: Crohn disease

F) forign body granuloma: e.g., suture or splinter

 The pathogenesis of granuloma:

1. Engulfment by macrophages: Macrophages and monocytes engulf the

2. CD4+ T cells. Macrophages, being antigen-presenting cells, having failed

3. Cytokines. Various cytokines formed by activated CD4+ T cells and also

i) IL-1 and IL-2: stimulate proliferation of more T cells.

ii)Interferon : activates macrophages.

iii) TNF- : promotes fibroblast proliferation

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