Chronic inflammation is characterized by prolonged inflammation lasting weeks or months, where tissue injury and attempts at repair occur simultaneously. It can be caused by persistent infections, prolonged exposure to toxic agents, or autoimmunity. Morphologically, it features infiltration by mononuclear cells like macrophages and lymphocytes, ongoing tissue destruction, and attempts at healing through fibrosis and angiogenesis. Chronic inflammation is regulated by various cell-derived mediators like cytokines, eicosanoids, and reactive oxygen species, as well as plasma-derived mediators like components of the complement, coagulation, and kinin systems. Granulomatous inflammation forms microscopic nodules called granulomas in an attempt to contain hard to eliminate infectious agents.

1. INFLAMMATION
Part - II

2. Definition of Chronic inflammation
Chronic inflammation is inflammation of prolonged duration
(weeks or months) in which inflammation, tissue injury, and
attempts to repair coexist.

3. Mechanism of chronic inflammation
Macrophages
Cytokines
Free
radicals
Enzymes
NO
TGF-B
FGE
GCSF
+
EGF
AngiogenesisFibrosis
Granulation tissueHealing
Activation
TH

4. Causes of Chronic inflammation
I - Persistent infection.
 Bacteria
 Viruses
 Fungi
 Parasites
II - Prolonged exposure to potentially toxic agents.
 Endogenous (atherosclerosis)
 Exogenous ( particulate silica-Silicosis)
III – Autoimmunity
 Rheumatoid arthritis
 Lupus erythematosus

5. Morphological Features of Chronic
Inflammation
These are characterized by:
I - Infiltration by mononuclear cells
II - Tissue destruction
III - Removal of damaged tissue (healing)

6. I - Infiltration by mononuclear cells:
The mononuclear cells become predominant after 48 hours
These include:
 Macrophages
 Lymphocytes
 Plasma cells
 Eosinophils
 Mast cells

7. Macrophages
 Scattered all over (microglia, Kupffer cells, sinus
histiocytes, alveolar macrophages)
 Circulate as monocytes and reach the site of injury within 24
– 48 hrs and transform
 Become activated by T cell-derived cytokines, endotoxins,
and other products of inflammation

10.  T and B lymphocytes
Antigen-activated (via macrophages)
Release macrophage-activating cytokines (in turn, macrophages
release lymphocyte-activating cytokines until inflammatory
stimulus is removed)
 Plasma cells
 Terminally differentiated B cells (of lymphocytes)
 Produce antibodies

11. Eosinophils
 Found especially at sites of parasitic infection, or at allergic
(IgE-mediated) sites.
 Eosinophils have highly cationic proteins, which are toxic to
parasites.

12. II - Tissue destruction
Occurs due to:
 Inflammatory cells
 Persistent infecting material

13. III - Removal of damaged tissue (healing):
 Occur by proliferation of small blood vessels (angiogenesis).
 Proliferation of fibroblast (fibrosis-repair).

14. Applied Aspects of Chronic Inflammation
 Lichen planus
 Leukoplakia
 Oral submucous fibrosis
 Periodontal disease

15. GRANULOMATOUS INFLAMMATION
 It is a cellular attempt to contain an offending agent that is
difficult to eradicate.
 A granuloma is a focus of chronic inflammation consisting of
a microscopic aggregation of macrophages that are transformed
into epithelium-like cells principally lymphocytes and
occasionally plasma cells.

16. Granuloma:
Bacilli/foreign body are inhaled by droplets
They are phagocytosed by alveolar macrophages
After amassing substances that they cannot digest, macrophages lose
their motility, accumulate at the site of injury and transform
themselves into nodular collections
A localized inflammatory response recruits more mononuclear cells
The granuloma consists of a kernel of infected macrophages surrounded
by foamy macrophages and a ring of lymphocytes and a fibrous cuff
(containment phase)
Containment usually fails when the immune status of the patient changes;
the granuloma caseates, ruptures and spills into the airway

17. GRANULOMA
EPITHELIOID CELLS
 Activated/Modified Macrophages
 Indistinct Cell Borders
 Pale Pink Cytoplasm
 Vesicular Nucleus-Slipper Sole Shaped
LYMPHOCYTES
 Usually form a cuff around Epithelial cells may be admixed
with plasma cells

18. GIANT CELLS
 Fusion of Epitheloid cells
 Langhans giant cells – Nucleus in periphery Horse shoe
manner.
 Foreign body – Haphazard arrangement
FIBROSIS
 Surrounding lymphocytes
 Burnt – out scarring

19. TWO MAIN TYPES BASED ON PATHOGENESIS –
FOREIGN BODY
Form when material such as talc, sutures, or other fibers are large
enough to preclude phagocytosis by a single macrophage.
IMMUNE
Caused by insoluble particles that are capable of inducing a cell-
mediated response
 Poorly degradable agent

20.  Central Necrosis is seen in some granulomas
 Epitheloid cells fuse to form giant cells containing 20 or more
nuclei.
 The nuclei arranged either peripherally (Langhans-type giant
cell) or
 Haphazardly (foreign body-type giant cell).
 These giant cells can be found either at the periphery or the
center of the granuloma.

21. Examples of granulomatous inflammation
 Tuberculosis
 Leprosy
 Syphillis
 Actinomycosis
 Cat Scratch Disease
 Berylliosis
 Foreign body

22. Sub acute inflammation
 Has features of acute inflammation but lasts longer
 Persists for weeks or months

23. CHEMICAL MEDIATORS
OF INFLAMMATION

24. Mediators of inflammation
Cell derived mediators
 Vasoactive amines
 Arachidonic acid metabolites
 Eicosanoids
 Prostaglandins
 Leukotrienes
 Platelet Activating Factor
 Cytokines
 ROS and NO
 Lysosomal constituents

25. Plasma derived mediators
 Clotting system
 Fibrinolytic system
 Kinin system
 Complement system

26. CELL DERIVED MEDIATORS

27. Vasoactive Amines
 They are released immediately during inflammation
 2 Types →
 Histamine
 Serotonin
Histamine – Causes →
 Dilation of arterioles
 Increases permeability of venules
Serotonin – Increases vascular permeability

28. Arachidonic Acid Metabolites
 Released from Membrane phospholipids through the action
of Cellular Phospholipases.
 On activation of cells membrane AA gets converted to →
 Prostaglandins – Produced by mast cells, macrophages and
endothelial cells
PGE2 – Hyperalgesic
 Leukotrienes – Secreted by Leucocytes
LTB4 – A potent chemotactic agent and activator of neutrophils
 Lipoxins – Inhibitors of inflammation
 Inhibit neutrophil chemotaxis and
 Its adhesion to endothelium

29. Platelet Activating Factor
 Phospholipid derived mediator
 Causes →
 Platelet aggregation
 Vasoconstriction , Bronchoconstriction
 Increased leukocyte adhesion to endothelium
 Chemotaxis

30. Reactive Oxygen Species
 Superoxide anion( O2
- ) , Hydrogen Peroxide (H2O2) ,
Hydroxyl radical (OH)
 After exposure to irritants, oxygen derived free radicals are
released from leukocytes
 Their extracellular release can increase the expression of
Chemokines, Cytokines and ELAM

31. Nitric Oxide (NO)
 Causes →
 Relaxation of vascular smooth muscles
 Promotes vasodilation
 Reduces platelet aggregation and adhesion
 Thus it is a mediator of host defense against infection.

32. Cytokines
 Proteins produced by activated lymphocytes, macrophages,
endothelial, epithelial and connective tissue cells.
 TNF and IL-1 mediate inflammation. Their effects are →
 “Endothelial Activation” which includes
 Expression of endothelial adhesion molecule
 Synthesis of chemical mediators
 Increase in surface thrombogenecity

33. Chemokines
 They act as Chemoattractants for specific type of leukocytes.
 Act as coreceptors for a viral envelop of glycoprotein of HIV 1
 Main functions →
 Stimulate leukocyte recruitment in inflammation
 Control normal migration of cells through various tissues.

34. Lysosomal constituents of Leukocytes
 Lysosomal granules are contained in Neutrophils and Monocytes
 Granule enzymes →
 Acid Proteases – Degrade bacteria and debris
 Neutral Proteases – Degrade extracellular components resulting
in tissue destruction.

35. Neuropeptides
 Substance P has functions like →
 Transmission of pain signals
 Regulation of blood pressure
 Increasing vascular permeability

36. PLASMA DERIVED MEDIATORS

37. Complement System
 Biologic functions fall into 3 categories →
 Inflammation – C3a , C5a mainly & to a lesser extent C4a
stimulate histamine release thus increasing vascular permeability
and cause vasodilation . These are called Anaphylatoxins.
 Phagocytosis – C3b act as Opsonins and promote Phagocytosis
 Cell lysis – Deposition of MAC on cells makes them permeable
to water and ions and thus results in lysis of cells.

38. Coagulation and Kinin System
 This system is activated by Factor XIIa
 Kinins are vasoactive peptides
 Bradykinin →
 Increases vascular permeability
 Causes contraction of smooth muscles
 Dilation of blood vessels
 Causes pain when injected into the skin

39. Clotting System
 Factor XIIa initiates the cascade of clotting system .
 Fibrinopeptides in inflammation causes →
 Increased vascular permeability
 Chemotaxis for leukocytes
 Anticoagulant activity

40. Fibrinolytic System
 Activated by Kallikrein, endothelial cells and leukocytes.

42. INTERVENTION IN INFLAMMATION

43.  Reducing inflammation
 Anti inflammatory agents
 NSAIDS
 Corticosteroids
 Removal of foreign body

44.  Minimize complications of edema
 Rest
 Ice
 Compression
 Elevation

45.  Monitor systemic response
 Fever – Antipyretics
 Diet – Calories, proteins, fluids, vit c rich diet

46. Self care at home
 Use of heat and cold application
 Follow medication regime
 Change dressings, maintain hygiene
 Early reporting if change in colour, appearance, or there is pain in
wound

49. References
1) Robbins Basic Pathology ,7th edition
2) Essential pathology, Harsh Mohan ,3rd edition
3) Wheater’s Basic Pathology ,5th edition
4) Inflammation by Trowbridge and Emling ,5th edition
5) Shafer’s Textbook of Oral Pathology, 6th edition