Power point presentation

1. INFLAMMATION
Dr. Shravya Shetty

2. CONTENTS:
 INTRODUCTION
 ACUTE INFLAMMATION
 VASCULAR CHANGES IN ACUTE INFLAMMATION
 CELLULAR EVENTS IN ACUTE INFLAMMATION
 CHEMICAL MEDIATORS OF INFLAMMATION
 CHRONIC INFLAMMATION
 ROLE OF LYMPHATICS AND LYMPH NODES IN
INFLAMMATION
 MORPHOLOGIC PATTERNS IN ACUTE AND CHRONIC
INFLAMMATION
 SYSTEMIC EFFECTS OF INFLAMMATION
 INTERACTION BETWEEN CANCER AND
INFLAMMATION
 CONCLUSION

3. INTRODUCTION:
 INFLAMMATION is a protective response intended
to eliminate the initial cause of cell injury as well as
the necrotic cells and tissues resulting from the
original result.
 A part of Innate immunity.
 It is a protective and beneficial host response of
the body against the offending agent, but it is also
capable of itself causing damage to the tissues.

4. CARDINAL SIGNS:
 First described by the Roman physician Cornelius Celcus in
the 1st century AD. The signs are :
- CALOR(heat)
- RUBOR(redness)
- TUMOR(swelling)
- DOLOR(pain)
 The FIFTH Cardinal sign was described by RUDOLPH
VIRCHOW in 1858:
- FUNCTIO LAESA(loss of function)
ACUTE
INFLAMMATION

5. ACUTE INFLAMMATION:
 Acute inflammation is a rapid response to injury or
microbes and other foreign substances that is designed to
deliver leukocytes and plasma proteins to sites of injury.
 ETIOLOGY:
 Infection-bacterial, viral, fungal, parasitic
 Trauma-blunt and penetrating
 Physical & Chemical agents-thermal injury
 Tissue necrosis
 Foreign bodies
 Immune reactions
 Has two major components:
-Vascular changes
-Cellular events

6. VASCULAR CHANGES:
 Brief arteriolar vasoconstriction followed by
vasodilation
 Accounts for warmth and redness
 Opens microvascular beds
 Increased intravascular pressure causes an early
transudate (protein-poor filtrate of plasma) into
interstitium (vascular permeability still not increased yet)

7. MECHANISMS CAUSING VASCULAR PERMEABILITY:

8. CELLULAR EVENTS
 2 events:
 Exudation of Leukocytes
 Phagocytosis

9. LEUKOCYTE CELLULAR EVENTS
 Leukocytes leave the vasculature routinely
through the following sequence of events:
 Changes in formed elements of blood
(Margination &Pavementing
 Rolling & Adhesion
 Emigration
 Chemotaxis
 They are then free to participate in:
 Phagocytosis and degranulation
 Leukocyte-induced tissue injury

11. LEUKOCYTE MIGRATION:

12. ENDOTHELIAL-LEUKOCYTE ADHESION
MOLECULES:

13. CHEMOTAXIS
 Leukocytes migrate toward sites of infection
or injury along a chemical gradient by a
process called chemotaxis.
 Chemotactic substances:
 Soluble bacterial products
 Complement components (C5a)
 Cytokines (chemokine family e.g., IL-8)
 LTB4 (Arachidonic Acid metabolite)
 Chemotactic agents bind to specific surface
receptors.

15. LEUKOCYTE ACTIVATION:

16. PHAGOCYTOSIS AND DEGRANULATION
 Once at site of injury, leukocytes:
 Recognize and attach
 Engulf (form phagocytic vacuole)
 Kill (degrade)

17. PHAGOCYTOSIS:
Opsonins: IgG,
C3b,
collectins
Myeloperoxidase
Lactoferrin,
Defensin,
Bactericidal
Permeability
Increasing
protein
OXIDATIVE
BURST
REACTION

18. LEUKOCYTE-INDUCED TISSUE INJURY
 Destructive enzymes may enter extracellular space
in event of:
 Premature degranulation
 Frustrated phagocytosis (large, flat)
 Membranolytic substances (urate crystals)
 Persistent leukocyte activation (Rheumatoid Arthritis,
Emphysema)

19. DEFECTS OF LEUKOCYTE FUNCTION
 Defects of adhesion:
 LFA-1 and Mac-1 subunit defects lead to impaired
adhesion (LAD-1)
 Absence of Sialyl-Lewis X, and defect in E- and P-
selectin sugar epitopes (LAD-2).
 Defects of chemotaxis/phagocytosis:
 Microtubule assembly defect leads to impaired
locomotion and lysosomal degranulation (Chediak-
Higashi Syndrome).
 Defects of microbicidal activity:
 Deficiency of NADPH oxidase that generates
superoxide, therefore no oxygen-dependent killing
mechanism (Chronic Granulomatous Disease).

20. CHEMICAL MEDIATORS
 Derived from plasma or local production by
cells. May or may not utilize a specific cell
surface receptor for activity.
 May also signal target cells to release other
effector molecules that either amplify or inhibit
initial response (regulation).
 Are tightly regulated:
 Quickly decay (AA metabolites), are inactivated
enzymatically (kininase), or are scavenged
(antioxidants)

21. CHEMICAL MEDIATORS
 Plasma-derived:
 Complement, kinins, coagulation factors.
 Many in “pro-form” requiring activation
(enzymatic cleavage).
 Cell-derived:
 Preformed, sequestered and released (mast cell
- histamine).
 Synthesized as needed (prostaglandin).

22. MEDIATORS OF INFLAMMATION:

23. SPECIFIC MEDIATORS
 VASOACTIVE AMINES :
 Histamine:
 Functions: Vasodilation and venular endothelial cell
contraction, junctional widening.
 Sources: Mast cells, basophils, platelets.
 Released in response to injury (trauma, heat),
immune reactions (IgE-mast cell FcR),
anaphylatoxins (C3a, C5a fragments), cytokines
(IL-1, IL-8), neuropeptides, leukocyte-derived
histamine-releasing peptides.

24. SPECIFIC MEDIATORS
 Serotonin:
 Functions: vasodilatory effects similar to those of
histamine.
 Source: platelet dense-body granules.
 Their release is triggered by platelet aggregation.
 PLASMA PROTEASES:
 Clotting system
 Complement
 Kinins

25. PLASMA PROTEASES:

26. CLOTTING CASCADE
 Cascade of plasma proteases
 Hageman factor (factor XII)
 Collagen, basement membrane, activated platelets
converts XII to XIIa (active form)
 Ultimately converts soluble fibrinogen to insoluble fibrin
clot
 Factor XIIa simultaneously activates the “brakes”
through the fibrinolytic system to prevent continuous clot
propagation

27. KININ SYSTEM
 Leads to formation of bradykinin from cleavage of
precursor (HMWK)
 Vascular permeability
 Arteriolar dilation
 Non-vascular smooth muscle contraction (e.g.,
bronchial smooth muscle)
 Causes pain
 Rapidly inactivated (kininases)

28. COMPLEMENT SYSTEM
 Components C1-C9 present in inactive form
 Activated via classic (C1) or alternative (C3)
pathways to generate MAC (C5 – C9) that punch
holes in microbial membranes.
 In acute inflammation:
 Vasodilation, vascular permeability, mast cell
degranulation (C3a, C5a)
 Leukocyte chemotaxin, increases integrin avidity
(C5a)
 As an opsonin, increases phagocytosis (C3b, C3bi)

29. SPECIFIC MEDIATORS
 Arachidonic acid metabolites (eicosanoids)
 Prostaglandins and thromboxane: via
cyclooxygenase pathway- cause vasodilation
and prolong edema; but also protective (gastric
mucosa); COX blocked by aspirin and NSAIDS

30. SPECIFIC MEDIATORS
 PAF (PLATELET ACTIVATING FACTOR):
 Derived also from cell membrane phospholipid.
 Produced by- neutrophils, mast cells, platelets and
endothelial cells.
 Acts through G-protein linked receptors.
 Functions: -Vasodilation,
- Increased vascular permeability
- - Increases leukocyte adhesion
(integrin conformation).

31. MORE SPECIFIC MEDIATORS
 CYTOKINES:
 Protein cell products that modulate the functions of the
other cells.
 Have autocrine,paracrine and endocrine effects
 IL-1, TNF- and -, IFN-, chemokines(IL-8) are
especially important in inflammation.
 Increase endothelial cell adhesion molecule expression-
endothelial activation;
 Activation and aggregation of PMNs, etc.,

32. SPECIFIC MEDIATORS
 NITRIC OXIDE:
 Short-acting(effects are localised) soluble free-
radical gas with many functions.
 Produced by endothelial cells, macrophages,
causes:
Vascular smooth muscle relaxation and
vasodilation.
Kills microbes in activated macrophages.
Counteracts platelet adhesion, aggregation,
and degranulation.

33. SPECIFIC MEDIATORS
 LYSOSOMAL COMPONENTS:
 Leak from PMNs and macrophages after demise,
attempts at phagocytosis etc.
 Acid proteases (only active within lysosomes).
 Neutral proteases such as elastase and
collagenase are destructive in ECM. Also cleave
C3 and C5 to form C3a and C5a.
 Counteracted by serum and ECM anti-proteases.

34. POSSIBLE OUTCOMES OF ACUTE INFLAMMATION
 Complete resolution
 Little tissue damage
 Capable of regeneration
 Involves- Neutralization/ removal of chemical mediators.
- Normalization of vascular permeability.
- Halting of leucocyte emigration.
 Scarring (fibrosis)
 In tissues unable to regenerate/ after substantial tissue destruction.
 Excessive fibrin deposition organized into fibrous tissue.
 Abscess formation occurs with some bacterial or fungal
infections.
 Progression to chronic inflammation.

35. CHRONIC INFLAMMATION
 Chronic inflammation is inflammation of prolonged
duration (weeks to months to years) in which active
inflammation, tissue injury, and healing proceed
simultaneously.
 Characterized by:
Infiltration with mononuclear cells, macrophages,
lymphocytes, and plasma cells.
Tissue destruction, largely induced by the
products of the inflammatory cells.
Repair, involving new vessel proliferation
(angiogenesis) and fibrosis.
Engorged blood vessel
Chronic Inflammatory
cell infilterate

36. CHRONIC INFLAMMATION:
Acute inflammation Chronic inflammation
Occurs when acute response cannot be resolved
because of :
Persistence of the injurious agent .
Interference with the normal process of
healing.

37. CHRONIC INFLAMMATION IS SEEN IN :
 Persistent infections which are difficult to eradicate.
 Diseases that are caused by excessive and inappropriate
activation of the immune system.
 Autoimmune diseases
 Allergic diseases
 Prolonged exposure to potentially toxic agents.

38. MONONUCLEAR PHAGOCYTE SYSTEM
 Macrophages
 Scattered all over (microglia, Kupffer cells, sinus
histiocytes, alveolar macrophages, etc.
 Circulate as monocytes and reach site of injury
within 24 – 48 hrs and transform.
 Become activated by T cell-derived cytokines,
endotoxins and other products of inflammation.

40. CELLS OF CHRONIC INFLAMMATION
 T and B lymphocytes
 Antigen-activated (via macrophages and dendritic cells)
 Release macrophage-activating cytokines (in turn,
macrophages release lymphocyte-activating cytokines
until inflammatory stimulus is removed)
 Plasma cells
 Terminally differentiated B cells
 Produce antibodies
 Eosinophils
 Found especially at sites of parasitic infection, or at
allergic (IgE-mediated) sites
 Granules contain Major Basic Protein(MBP)– Toxic to
parasites, also cause tissue damage.

41. GRANULOMATOUS INFLAMMATION
 Clusters of T cell-activated macrophages, which
engulf and surround indigestible foreign bodies
(mycobacteria, H. capsulatum, silica, suture
material)
 Resemble squamous cells, therefore called
“epithelioid” granulomas

42. DISEASES WITH GRANULOMATOUS
INFLAMMATION:
DISEASE CAUSE TISSUE REACTION
Tuberculosis Mycobacterium
tuberculosis
Caseating granuloma(tubercle); focus of
activated macrophages(epithelioid cells),
rimmed by
fibroblasts,lymphocytes,histiocytes,
occasional Langhans giant cells; central
necrosis with amorphous granular
debris;acid-fast bacilli
Leprosy Mycobacterium leprae Acid-fast bacilli in macrophages;non-
caseating granulomas.
Syphilis Treponema pallidum Gumma:microscopic to visible lesion;
enclosing wall of histiocytes;plasma cell
infiltrate; central cells necrotic without
loss of cellular outline
Actinomycosis Actinomycetes israelii Granulomas and abscesses with draining
sinuses; sulphur granules

43. What are the differences
between acute and chronic
inflammation??

44. FEATURES ACUTE INFLAMMATION CHRONIC INFLAMMATION
Duration Short-lived,
only a few days
Several weeks, months to years
Causative agent Harmful bacteria
or
injury to tissue
•Non-degradable pathogens that
cause persistent inflammation
•Viral infection
• Persistent foreign bodies
•Overactive immune system
reactions
Major cells
involved
Mainly Neutrophils,
Basophils , Eosinophils,
Mononuclear Cells
Mononuclear Cells, Lymphocytes
And Fibroblasts
Primary
Mediators
Eicosanoids, Vasoactive
Amines
Reactive Oxygen Species,
Hydrolytic Enzymes, IFN-γ &
Other Cytokines

45. RESPONSE OF LYMPHATIC VESSELS
 Lymphatics also participate in the inflammatory
response.
 Normal condition-A small amount of interstitial fluid -
removed by lymphatic drainage.
 Inflammation- lymph flow - increased and drains the
edematous fluid from extravascular space- junctions
are loose and leaky ; lymphatic fluid equilibrates with
extra-vascular fluid.
 Along with fluid, leucocyte and cell debris- drain into
the lymph.
 Severe Inflammation- lymphatics transport the
offending agent.

46.  Lymphatics get secondarily
inflammed
Draining Lymph nodes get secondarily
inflammed
Draining lymph nodes enlarge
due to- hyperplasia of lymphoid follicles
- number of lymphocytes and
phagocytotic cells lining the
sinuses of lymph node.
Presence of red streaks near the skin wound
-red streaks follow the course of lymphatic channels
-diagnostic of lymphangitis and lymphadenitis.
LYMPHANGITIS
LYMPHADENITIS
REACTIVE/
INFLAMMATORY
LYMPHADENITIS

47. MORPHOLOGIC PATTERNS OF ACUTE AND CHRONIC
INFLAMMATION:
 Serous:
 Watery, protein-poor effusion (e.g., blister)
 Fibrinous
 Fibrin accumulation
 It appears like a meshwork of thread / an amorphous coagulum.
 Removed by- fibrinolysis or macrophages- resolution
 If fibrin is not removed- ingrowth of fibroblasts & blood vessels 
scarring.
 Suppurative
 Presence of pus / purulent exudate  neutrophils,necrotic cells
and edema fluid  produced by pyogenic organisms
 Often walled-off if persistent.
 Ulcers
 Local defect / excavation of the surface – produced by sloughing
 Seen in mucosa of the mouth, intestine etc..

48. SYSTEMIC EFFECTS OF INFLAMMATION:
 Fever- IL-1, IL-6, PGE and TNF- Act on the
Hypothalamus
 Increase in the Acute Phase Proteins- C- Reactive
Protein, Fibrinogen, Serum Amyloid A protein.
 Leukocytosis-IL-1 and TNF, In prolonged infections-
colony stimulating factor.
 Neutrophilia, Lymphocytosis, Eosinophilia.
 Increase in pulse and blood pressure; decreased
sweating.
 Septic shock

49. INTERACTION BETWEEN CANCER AND
INFLAMMATION:

50.  OSMF- Potentially malignant disease- habitual use of
arecanut / betel quid.
 Charecterised by
- dense fibrosis of lamina propria
-juxta-epithelial inflammatory reaction(lymphocytes, plasma cells,
macrophages).
-atrophy / hyperplasia of over-lying epithelium.
 Chemical agents of betel quid produce- PGs,ROS, TNF-α,
IL-8 ,IL-6, TGF-β, PDGF and basic fibroblast growth factor.
FIBROSIS.
 Components of betel quid- mutagenic.
 PGE-2, IL-6, TNF-α  favours malignant transformation.

51.  Oral Lichen Planus- T-cell mediated immuno-inflammatory
reaction against an undefined antigen within basal cell
layer of oral epithelium.
 Up-regulation of - IL-6, TGF-β, TNF-α  in cases of LP
evolving to OSCC, inflammatory mediators provides
that activate transcription factors- promote longevity &
proliferation of cells, angiogenesis, invasion and
 In established OSCC- TNF-α , IL-6  proliferation of
cells and survival, tumor growth promotion via
expression of Cell adhesion molecules & ECM proteins.
 High levels of COX-2 invasion, metastasis, recurrence
poor prognosis.

52. CONCLUSION:
 Wounds wouldn’t heal.
 Minor infections would become overwhelming.
 Prolonged inflammation might lead to
transformation into cancers.
 Important to understand it well enough to avoid it’s
unpleasant aspects

53. REFERENCES:
 Kumar, Abbas, Fausto, Mitchell: Acute and Chronic
Inflammation. In Robbins Basic Pathology, 8th Ed.
Elsevier 2010, 33-58.
 Kumar, Abbas, Fausto, Mitchell: Acute and Chronic
Inflammation. In Robbins Basic Pathology, 6th Ed.
Elsevier 1997,25-46 .
 Cotran, Kumar, Robbins: Acute and Chronic
Inflammation. In Robbins Pathologic Basis of
Disease, 5th Ed. Saunders 1994,51-91.
 Cawson. Binny, Eveson: Color Atlas of Oral
Disease, clinical and pathological correlations, 2nd
Ed. Wolfe1994, fig 3.18, 4.5, 16.8.

54. REFERENCES:
 Ricciotti E , FitzGerald G.A.:Prostaglandins and
Inflammation. Arterioscler Thromb Vasc Biol.
2011;31:986-1000
 L. Feller , M. Altini , J. Lemmer: Inflammation in the
context of oral cancer. Oral Oncology 49 (2013)
887–892