chronic inflammation composed by ahmad, deptt of pharmacy university of peshawar 2010

1. Composed by:
Ahmad wali
3rd prof (M)

2. Definition:
Inflammation is a protective response intended to
remove injurious stimuli as well as the necrotic cells
and tissues resulting from original insert.
OR
Repair process that causes the replacement of damaged
tissues by regeneration of parenchyma cells or by
filling of any residual defect by firous scar tissues.

3. ADVANTAGES:
 It causes destruction of microbes.
 Causes detoxification of toxins.
 Clears infections.
 Helps in healing process.
 Causes repair of damaged tissues.

4. DISADVANTAGES:
Inflammatory responses are sometimes harmful as they
cause:
 Life threatening anaphylactic reactions to insects
bites, drugs and other chronic diseases like
Rheumatoid arthritis, Atherosclerosis etc.
 Inflammation of peritoneum leads to firous bands that
causes obstruction of intestines.
 Pericardial inflammation causes the formation of
dense pericardium that impairs cardiac functions.

5. PLAYERS OF INFLAMMATION:
The inflammatory responses have many players. They
include:
1) CIRCULATING CELLS:
I. Bone marrow derived polymorph nuclear leukocytes
e.g., Basophils, Esinophils and Neutrophils.
II. Lymphocytes
III. Monocytes
IV. Platelets.
2) CIRCULATING PROTEINS:
I. Clotting factors
II. Kininogens
III. Complement proteins

6. 3) VASCULAR WALL CELLS:
I. Connective tissue cells
II. Smooth muscle cells
III. Epithelial cells
4) EXTRA CELLULAR MATRIX:
I. Fibrous structural proteins e.g., Elastin & Fibrinogen
II. Gel-forming proteoglycans
III. Adhesive glycoprotein e.g., Fibronectin, that are cell-
ECM and ECM-ECM connectors.

7. Inflammatory stimulus Chemical mediators
Inflammatory response until
injurious stimulus is removed
When the inflammatory stimulus is removed these
mediators are then dissipated, catabolized or removed.
TYPES OF INFLAMMATION:
 Acute inflammation
And
 Chronic inflammation

8. Chronic inflammation is the inflammation with
prolonged duration usually from weeks to months and
sometimes to years in which active inflammation,
tissue injury and healing process proceed
simultaneously.
DISTINGUISHING FEATURES:
 Infiltration of mono-nuclear cells like lymphocytes,
macrophages and plasma cells.
 Destruction of tissue by inflammatory cells.
 Proliferation of new vessels leading to repair
(angiogenesis & fibrosis).

9. ORIGIN AND PROCESS:
Chronic inflammation arises from acute inflammation.
This transition takes place if the acute responses cannot
be resolved either because of the persistence e.g., of
injurious stimuli or by interference of the normal
healing process e.g., peptic ulcer.
Some types of injuries engender responses with chronic
inflammation initially e.g., viral infections.
SETTINGS LEADING TO CHRONIC INFLAMMATION:
I. Viral infections
II. Persistent microbial infections
III. Prolonged exposure to potentially toxic materials
IV. Autoimmune diseases

10. It is joined by lymphocytes and plasma cells,
however mast cells and eosinophils are as well involved
in chronic allergic diseases
Blood monocytes Tissue macrophage (RES)migrate into
tissue
within 48 hours
after injury
and differentiate
Kupffer cell
(liver)
Microglia (CNS)
Histiocytes
(spleen)
Alveolar macs
(lung)
Lymphocyte Plasma cell

11. CHRONIC INFLAMMATORY CELLS & MEDIATORS:
1) MACROPHAGES:
Macrophages are white blood cells within tissues, produced
by the division of monocytes.
A majority of macrophages are stationed at strategic points
where microbial invasion or accumulation of dust is likely
to occur. Each type of macrophage, determined by its
location, has a specific name:
 In liver Kupffer cells
 Spleen and lymph nodes Sinus histocytes
 Nervous system Microglial cells
 Lungs Alveolar macrophages

12. During chronic inflammation macrophages serve to eliminate injurious
agents and initiate repair- however, they are as well responsible for much
of the tissue injury that occurs
IFN-g
Activated T cell or NK cell
Tissue macrophage
Activated macrophage
Non Immune activation:
Endotoxins,
fibronectin,
chemical mediators
Tissue injury
Toxic oxygen metabolites
Metallo-proteases
Coagulation factors
AA metabolites and NO
Fibrosis (Scaring)
Growth factors involved
in fibroblast proliferation
(PDGF,TGFb,FGF)
Angiogenesis factors
(FGF,VEGF)
Collagen deposition
(IL-13 and TGFb)

13. FUNCTIONS OF MACROPHAGES:
They help to:
 Filter the particulate matter
 Kill microbes
 Alert immune system of the body.
 Their life is 1-2 days.
ACTIVATION OF MACROPHAGES:
Activation of macrophages means:
 Increase in size
 Increase in lysosomal content
 Increase in metabolism
 Increase in microbial killing activity

14. ACTIVATION SIGNALS:
Different signals required to activate macrophages are:
 Cytokines produced by T-lymphocytes
 Bacterial endotoxins
 Different mediators produced during acute
inflammation
 Extra cellular matrix proteins e.g., Fibrinogen
When macrophages become activated they produce
different type of biologically active substances that
either cause ;
Cell injury
OR
Fibrosis.

15. Cell injury causing substances:
 Acid and neutral proteases
 Complement proteins C1 to C5
 Coagulating factors V & VШ
 Amino acids metabolites
 Cytokines
 Tumor necrosis factor
Fibrosis causing substances:
 Growth factors
 Fibrogenic cytokines
 Angiogenesis factors
 Regeneration and remodeling factors

16. 2) LYMPHOCYTES:
Both T- & B-lymphocytes are involved in chronic
inflammation. Their migration is brought about by
specific adhesion molecules and cytokines. The T-
lymphocytes work in reciprocal with B-lymphocytes in
chronic inflammation. The already activated
macrophages release TNF & IL1 and activate the
inactive lymphocytes which then produce different
antibodies that cause destruction of antigens at the
inflammatory site.
3) ESINOPHILS:
They are usually found in parasitic infections and IgE
mediated allergic reactions. Their migration is brought
about by adhesion molecules produced by leukocytes
and epithelial cells. Esinophils specific granules
contain Major Basic Proteins which is highly cationic
&toxic for parasites.

17. 4) MAST CELLS:
Mast cells are tissue cells which are like basophils in
shape. They are present in bone marrow and around
blood vessels and do not enter the blood. They are
specifically armed with IgE antibodies against certain
antigens. When these antigens are encountered, they
release histamines and amino acid metabolites. They
cause initial vascular changes in acute inflammation
and also cause anaphylactic reactions.

18. TYPES OF CHRONIC INFLAMMATION:
1) AGRANULOMATOUS:
Granuloma is not formed,
Inflammation is characterized by all features of chronic
inflammation.
Examples:
 Chronic viral infections e.g., Hepatitis
 Chronic autoimmune diseases e.g., Rheumatoid
arthritis and Ulcerative colitis
 Chronic chemical intoxication e.g., Chronic
alcoholic liver disease
 Allergic reactions e.g., Bronchial asthma

19. 2) GRANULOMATOUS INFLAMMATION:
Characterized by aggregates of activated macrophages
that assume a squamous cell like epithelloid
appearance.
GRANULOMA is defined as aggregates of macrophages
formed due persistant response of T-lymphocytes to
particular antigens.
This has a granular cheesy appearance called as caseous
necrosis.
Examples are:
Bacterial:
Tuberculosis , Leprosy, Syphilis gumma etc.

20. Parasitic:
Schistosomiasis
Fungal:
Histoplasma capsulatum, Blastomycosis.
Inorganic metals / Dust:
Silicosis
Foreign bodies:
Suture, Vascular graft.
Unknown:
Sarcodiosis.

21. Best Regards
pharmacy2k10@yahoogroups.com