INTRODUCTION HISTORY CAUSES OF INFLAMMATION CLASSIFICATION ACUTE INFLAMMATION CHEMICAL MEDIATORS OF INFLAMMATION OUTCOMES OF ACUTE INFLAMMATION CHRONIC INFLAMMATION INFLAMMATORY DISEASES REFERENCES

1. INFLAMMATION

2. CONTENTS
 INTRODUCTION
 HISTORY
 CAUSES OF INFLAMMATION
 CLASSIFICATION
 ACUTE INFLAMMATION
 CHEMICAL MEDIATORS OF INFLAMMATION
 OUTCOMES OF ACUTE INFLAMMATION
 CHRONIC INFLAMMATION
 INFLAMMATORY DISEASES
 REFERENCES

3. INTRODUCTION
 Inflammation is defined as a protective response involving
host cells, blood vessels, and proteins and other mediators that
is intended to eliminate the initial cause of cell injury, as well as
the necrotic cells and tissues resulting from the original insult,
and to initiate the process of repair (ROBBINS).
 Term inflammation is derived from Latin word ‘inflammare’ =
‘to burn’.
 Our Principal safeguard against injury
 Fundamentally designed to localize and eliminate the
causative agents & limit tissue injury.
 Majority of lesions are named by adding suffix – itis=
belonging to.

4. HISTORY
 Egyptians first described in 3000 B.C
 Celsus (1st century AD) − 4 cardinal signs of inflammation
 Virchow- fifth sign functio laesa (loss of function)
 John Hunter (1973) − inflammation is not a disease but a nonspecific
response that has a salutary effect on its host.
 Julius Conheim (1839 to 1884) described the process of
inflammation.
 In 1924 Lewis explained role of chemical mediators in inflammation.

5. CAUSES OF INFLAMMATION
Physical agents - mechanical injuries, alteration in
temperatures and pressure, radiation injuries.
Chemical agents- including the ever increasing lists of drugs
and toxins.
Biologic agents (infectious)-bacteria,viruses,fungi, parasites
Immunologic disorders- hypersensitivity reactions,
autoimmunity,immunodeficiency states etc
Genetic/metabolic disorders- examples gout, diabetes
mellitus etc.

6. HOW IS INFLAMMATION DIFFERENT FROM INFECTION?
 Infection is invasion into the body by harmful microbes and their
resultant ill effects by toxins.
 Protective mechanism of body against various etiological agents.

7. CLASSIFICATION
 Based on duration of the lesion and histologic appearances
CHRONIC ACTIVE INFLAMMATION
 is the type of chronic inflammation in which during the course
of disease there are acute exacerbations of activity.

8. Steps of Inflammation 5R’s
1. Recognition of injurious agent
2. Recruitment of leukocytes
3. Removal of agent
4. Regulation of the response
5. Resolution
SEQUENCE OF EVENTS

9. ACUTE INFLAMMATION
 Acute inflammatory response by the host to any agent is a continuous
process involving
ACUTE
INFLAMMATION
VASCULAR
EVENTS
HAEMODYNAMIC
CHANGES
ALTERED
VASCULAR
PERMEABILITY
CELLULAR
EVENTS
EXUDATION OF
LEUKOCYTES
PHAGOCYTOSIS

10. I.VASCULAR EVENTS
A. HAEMODYNAMIC CHANGES:
1. TRANSIENT VASOCONSTRICTION
2. VASODILATATION (arterioles, venules and capillaries)
obvious within half an hour of injury
Increase blood volume in microvascular bed Redness
and warmth
3. Elevation of HYDROSTATIC PRESSURE
Results in transudation of fluid in the extracellular space
swelling

11. Increased vascular permeability
Increased concentration of RBCs
Raised blood viscosity
Slower blood flow
slowing followed by
5.LEUCOYTE MARGINATION (neutrophils mainly) to the
vascular endothelium
Leukocytes then move and migrate through gaps between the
endothelial cells in the extravascular space.
4. Slowing or stasis

12. LEWIS EXPERIMENT:
 Lewis induced the changes in the skin of the inner aspect of
forearm by firm stroking with a blunt point. The reaction so
elicited is known as
TRIPLE RESPONSE or RED LINE RESPONSE consisting of :
 RED LINE- local vasodilatation of capillaries and venules
 FLARE - vasodilatation of adjacent arterioles
 WHEAL - transudation of fluid into the extravascular space

13. B. ALTERED VASCULAR PERMEABILITY
 In normal circumstances fluid balance is maintained by 2
opposing set of forces:
1. Forces that cause OUTWARD MOVEMENT of fluid from
microcirculation are intravascular hydrostatic pressure and
osmotic pressure of interstitial fluid.
2. Forces that cause INWARD MOVEMENT of interstitial fluid
into circulation are intravascular osmotic pressure and
hydrostatic pressure of interstitial fluid.
STARLING’S HYPOTHESIS

14.  Normally whatever little fluid is left in the interstitial
compartment is drained by the lymphatics and thus no
oedema results.
 In inflamed tissues, the endothelial lining becomes leaky.
Consequently, the intravascular osmotic pressure decreases
and osmotic pressure of the interstitial fluid increases
resulting in excessive outward flow of fluid into the interstitial
compartment. EXUDATIVE INFLAMMATORY OEDEMA

15. MECHANISMS OF INCREASED VASCULAR PERMEABILITY

16. A. EXUDATION OF LEUCOCYTES
 Most important feature of inflammatory response.
 The escape of leucocytes from lumen of microvasculature to
the interstitial tissue.
 In acute inflammation, polymorphonuclear neutrophils
comprise the first line of defense, followed later by the
monocytes and macrophages.
II.CELLULAR EVENTS
CHANGES LEADING TO MIGRATION
1. CHANGES IN THE FORMED ELEMENTS OF BLOOD
 The normal axial flow consists of central stream of cells
comprised by leucocytes and RBCs and peripheral cell-free
layer of plasma close to vessel wall

17. VASODILATATION subsequently, SLOWING of BLOOD STREAM
The central stream of cells widens and peripheral plasma zone
becomes narrower because of loss of plasma by exudation.
MARGINATION
The neutrophils of the central column come close to the vessel
wall
PAVEMENTING

18. 2. ROLLING AND ADHESION:
Peripherally marginated and pavemented neutrophils slowly roll
over the endothelial cells lining the vessel wall.
ROLLING PHASE
Transient bond between the leucocytes and the endothelial cells
becoming firmer.
ADHESION PHASE

19. SELECTINS :
E-selectin (cytokine-activated Endothelial cells)
P-selectin (Preformed and stored in endothelial cells)
L-selectin (expressed on surface of Lymphocytes and neutrophils)
INTEGRINS:
Activated during the process of loose and transient adhesions
between the endothelial cells and leucocytes.
IMMUNOGLOBULIN GENE SUPER FAMILY ADHESION
MOLECULE:
ICAM-1,VCAM-1.
ADHESION MOLECULES:

20. 3. EMIGRATION
Neutrophils move till a suitable site is reached
CYTOPLASMIC PSEUDOPODS
Subsequently, crosses the basement membrane by damaging it
locally with secreted collagenases and escape out into the
extravascular space.
EMIGRATION

21. Simultaneously escape of RBCs takes place through the gaps
between the endothelial cells.
DIAPEDESIS
Diapedesis gives Hemorrhagic appearance to the inflammatory
exudate.
DIAPEDESIS

22.  The chemotactic factor mediated transmigration of leucocytes
after crossing several barriers to reach the interstitial tissues is
called CHEMOTAXIS.
 Well illustrated by BOYDEN’S CHAMBER EXPERIMENT.
 In this, a millipore filter separates the suspension of
leucocytes from the test solution in tissue culture chamber.
 If the test solution contains chemotactic agent, the leucocytes
migrate through the pores of filter towards the chemotactic
agent.
4. CHEMOTAXIS

23. The following agents act as potent chemotactic substances
for neutrophils:
i) Leukotriene B4 (LT-B4).
ii) Components of complement system (C5a and C3a in
particular).
iii) Cytokines (Interleukins, in particular IL-8)
iv) Soluble bacterial products (such as formylated peptides).

24. B. PHAGOCYTOSIS
 ENGULFMENT of solid particulate material by the cells (cell
eating).
The cells performing this function are PHAGOCYTES.
There are two main types of cells:
1. PMNs which appear early in acute inflammatory response and
are called as MICROPHAGES.
2. Circulating monocytes and fixed tissue mononuclear
phagocytes called as MACROPHAGES.
The process of phagocytosis is same for both polymorphs and
macrophages and involves 3 steps:

25. RECOGNITION AND ATTACHMENT OF PARTICLE
ENGULFMENT WITH FORMATION OF PHAGOCYTIC VESICLE
KILLING & DEGRADATION STAGE

26. CHEMICAL MEDIATORS OF INFLAMMATION
 Also called as PERMEABILITY factors or ENDOGENOUS
factors.
 The substances acting as chemical mediators of inflammation
may be released from the cells, the plasma, or damaged tissue
itself.

27. VASOACTIVE AMINES
HISTAMINE
SOURCE :
1) Mast cells in C.T adjacent
to blood vessels
2) Blood basophils
3) Platelets
STIMULI :
 Injury
 Immune reactions
 Fragments of complement
 -C3a , C5a
 Neuropeptides such as
 substance P
 Cytokines IL – 1 , 8
SEROTONIN
SOURCE :
1) Platelets
2) Enterochromaffin cells
3) nervous tissue
4) mast cells
STIMULI :
 Platelet aggregation after
contact with collagen ,
 thrombin
Action: vasodilatation, increased vascular permeability, itching
and pain

28. ARACHIDONIC ACID METABOLITES
A fatty acid with 2 main sources :
 Directly through diet
 Through conversion of essential fatty acid, linoleic acid to
arachidonic acid
ARACHIDONIC ACID
ARACHIDONIC
ACID METABOLITES
Cyclo-oxygenase pathway
Lipo-oxygenase Pathway
CYCLO – OXY- GENASE
PATHWAY
• Prostaglandin - PGD2 , E2 ,
F2.
• Thromboxane A2
• Prostacyclin
LIPO – OXY – GENASE
PATHWAY
 5 – HETE
 Leukotrienes

30. LYSOSOMAL COMPONENTS
GRANULES OF NEUTROPHILS:
PRIMARY
• MPO
• ACID HYDROLASES
• ACID PHOSPHATASE
• PHOSPHOLIPASE
• PROTEASES
SECONDARY
• COLLAGENASE
• ALKALINE PHOSPHATASE
• LACTOFERRIN
• LYSOZYME
GRANULES OF MONOCYTES AND TISSUE MACROPHAGES:
ACID PROTEASE
COLLAGENASE
ELASTASE
PLASMINOGEN ACTIVATOR

31. First described in early 1970’s by Jacques Benvinste
Source:
 Platelets
 Basophils
 Mast cells
 Neutrophils
 Macrophages
 Endothelial Cells
 Platelet aggregation
 Vasoconstriction and Bronchoconstriction
 At extreme low concentration cause vasodilation,
increased vescular permeability
 Increased leukocyte adhesion
 Chemotaxis
Platelet Activating Factor
Functions:

32. CYTOKINES/CHEMOKINES
 proteins produced mainly by- activated lymphocytes &
macrophages , also from endothelium, epithelium &
connective tissue cells.
 Molecularly defined cytokines are called Interleukins
 Produced rapidly in response to noxious stimuli as part of
innate immunity
 Includes IL-1, IL-6, IL-8, Tumour necrosis factor (TNF- a nd b),
Interferon (IFN)-gamma Other chemokines (IL-8, MCP-1,
eotaxin, PF-4)

33. CYTOKINE CELL SOURCE MAIN ACTION
IL-1 Monocytes/macrophages. • Emigration of neutrophils and macrophages
• Role in fever and shock
IL-6 Monocytes/macrophages. • Hepatic production of acute phase protein
• Differentiation and growth of T and B cells
IL-8 Monocytes/macrophages, T
cells, neutrophils.
• Induces migration of neutrophils, macrophages and T cells
• Stimulates release of histamine from basophils
• Stimulates angiogenesis
TNF-α Monocytes/macrophages,
mast cells/ basophils.
• Hepatic production of acute phase protein
• Systemic features (fever, shock, anorexia)
• Enhanced leucocyte cytotoxicity
• Induction of pro-inflammatory cytokines
IFN- g T cells, NK cells All cells • Activation of macrophages and NK cells
• Stimulates secretion of Igs by B cells
• Differentiation of T helper cells
MCP-1 Fibroblasts, smooth muscle
cells.
• Chemoattractant for monocytes, T cells and NK cells
• Stimulates release of histamine from basophils
PF-4 Platelets, megakaryocytes
Fibroblasts, endothelial
cells
• Chemoattractant for fibroblasts
• Inhibitory to haematopoietic precursors and endothelial cell
proliferation
Major cytokines in inflammation

34. Chemokines:
Chemokines are a family of small proteins that act primarily as
chemoattractants for specific type of leukocytes.
GROUP TYPE OF CHEMOKINE FUNCTION
C – X – C IL-8 Activation and
chemotaxis of
Neutrophils
C – C MCP-1
Eotaxin
MIP-1
RANTES
Attracts Monocytes,
eosinophil, basophils
and lymphocytes but
NOT Neutrophils
C Lympholactin Specific for
lymphocytes
C – X3 – C Fractalkine Chemoattractant for
monocytes and T cells

35. OXYGEN METABOLITES
 Released by activated neutrophils and macrophages.
 Superoxide oxygen, hydrogen peroxide , hydroxl ion.
ACTION :
 Endothelial cell damage and thereby increasing vascular
permeability
 Damage to cells and tissue matrix by activating protease and
inactivating anti protease

36. NITRIC OXIDE
 is formed by activated macrophages during the oxidation of
arginine by the action of enzyme, NO synthase.
 NO plays the following roles in mediating inflammation:
a) mediates in vascular dilation
b) Anti-platelet activating agent
c) Possibly microbicidal action

37. PLASMA DERIVED MEDIATORS
(factor
XII)
KININ
SYSTEM
COMPLEMEN
T SYSTEM
CLOTTING
SYSTEM
FIBRINOLYTI
C SYSTEM

38. 1. THE KININ SYSTEM
 Vasoactive peptides derived from plasma proteins called
kininogens by action of proteases called kallikreins.
 Braykinin increases vascular permeability; contraction of
smooth muscle; dilation of blood vessels; pain when injected
into skin

39. 2.THE CLOTTING SYSTEM
The actions of fibrinopeptides in inflammation are:
 increased vascular permeability
 chemotaxis for leucocyte
 anticoagulant activity.

40. 3.FIBRINOLYTIC SYSTEM
 Kallikrein along with plasminogen activator converts
plasminogen to plasmin.
 Plasmin acts on fibrin & forms fibrin split products.
 Plasmin also activates C3 to C3a

41.  Complement activation elaborates several cleavage products
which mediate in inflammatory response
 Critical step in activation is the proteolysis of C3. This can
occur in 3 pathways:
 Classic pathway
 Alternate pathway
 Lectin pathway
4.Complement System

42. Role of Mediators in Different Reactions of Inflammation

43. OUTCOMES OF ACUTE INFLAMMATION
 Resolution,
 Healing by scarring (fibrosis),
 Chronic inflammation

44. CHRONIC INFLAMMATION
Definition: Chronic inflammation can be defined as a prolonged
inflammatory process(weeks or months) where an active
inflammation, tissue destruction and attempts at repair are
proceeding simultaneously.
CAUSES:
1.Persistent infections
Certain microorganisms associated with intracellular infection
such as tuberculosis, leprosy, certain fungi etc.
2.Prolonged exposure to nondegradable but partially toxic
substances either endogenous lipid components which result
in atherosclerosis or exogenous substances
such as silica, asbestos.

45. 3. Progression from acute inflammation:
Acute inflammation almost always progresses to chronic
inflammation
4.Autoimmunity:
Autoimmune diseases such as rheumatoid arthritis and systemic
lupus erythematosis are chronic inflammations from the outset.

46. Chronic inflammation is of two types
Specific - when the injurious agent causes a characteristic
histologic tissue response e.g. tuberculosis, leprosy, syphilis
Non-specific - when the irritant substance produces a
nonspecific chronic inflammatory reaction with formation of
granulation tissue and healing by fibrosis e.g. chronic
osteomyelitis, chronic ulcer.

47. CELLS OF CHRONIC INFLAMMATION
Monocytes and Macrophages are the primary cells.
These cells constitute the mononuclear- phagocytic system.
Macrophages are scavenger cells of the body.
T-Lymphocytes are primarily involved in cellular immunity
B-lymphocytes and Plasma cells produce antibodies.
Mast cells and eosinophils appear predominantly in response
to parasitic infestations & allergic reactions.

48. FEATURES OF CHRONIC INFLAMMATION
1.Mononuclear cell infiltration – phagocytes and lymphoid cells
macrophages- most important cells
2. Tissue destruction or necrosis
proteases, elastases, cytokines etc released by activated
macrophages
3. Proliferative changes- blood vessels and fibroblasts proliferate
forming granulation tissue.
thereby healing by fibrosis and collagen laying.

49. GRANULOMATOUS INFLAMMATION
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.
The word ‘granuloma’ is derived from granule meaning
circumscribed granule-like lesion, and -oma which is a suffix
commonly used for true tumours.

50. PATHOGENESIS OF GRANULOMA.

51. INFLAMMATORY DISEASES
 Gingivitis
 Periodontitis
 Osteomyelitis
 Cellulitis
 Pericoronitis
 Sialadenitis
 Glossitis.

52. GINGIVITIS
 Inflammation of gingiva is termed as gingivitis.
 Bleeding on probing – earliest sign of gingivitis
 Gingivitis is classified into four stages
1. Initial lesion
2. Early lesion
3. Established lesion
4.Advanced lesion

53. STAGES OF GINGIVITIS

54. CLINICAL FEATURES
 Bleeding on probing is present
 Color : red to bluish red
 Consistency : soft, friable
 Texture : loss of stippling is seen
 Size : Swollen or ballooning of interdental papilla and/or
gingival margin.
 Shape and contour : Blunts the marginal and papillary tissues

55.  Elimination of the etiologic factors: plaque, calculus by scaling
and root planning
 Correction of plaque retentive factors such as over contoured
crowns, overhanging margins, narrow embrasure spaces,
open contacts, ill fitting fixed or removable partial dentures,
tooth malposition.
MANAGEMENT

56. PERIODONTITIS
It is “an inflammatory d/s of supporting tissues of teeth caused
by specific microorganisams,resulting in progressive destruction
of periodontal ligament &alveolar bone with pocket
formation,recession or both”.
 Onset - any age; most common in adults
 Plaque initiates condition
 Subgingival calculus common finding
 Slow-moderate progression; periods of rapid progression
possible
 Modified by local factors/systemic factors/stress/smoking

57. Extent:
• Localized: <30% of sites affected
• Generalized: > 30% of sites affected
Severity: entire dentition or individual teeth/site
• Slight = 1-2 mm CAL(clinical attachment loss)
• Moderate = 3-4 mm CAL
• Severe = 5 mm CAL

58.  Gingiva moderately swollen
 Deep red to bluish-red tissues
 Blunted and rolled gingival margin
 Bleeding and/or suppuration
 Plaque/calculus deposits
 Variable pocket depths
 Loss of periodontal attachment
 Horizontal/vertical bone loss
 Tooth mobility
CLINICAL FEATURES

59. The treatment consists of –
1. Non-surgical procedures
• Scaling
• Root planing
• Curettage
2. Surgical procedure
• Pocket reduction surgery
• Resective
• Regenerative
• Correction of morphological / anatomic defects
MANAGEMENT

60. OSTEOMYELITIS
Osteomyelitis may be defined as “an inflammatory condition of
bone, that begins as an infection of medullary cavity and
haversian systems of the cortex & extends to involve the
periosteum of the affected area.”
PREDISPOSING FACTORS
• Fractures due to trauma and road traffic accidents
• Gun shot wounds
• Radiation damage
• Paget`s disease
• Osteoporosis
• Systemic disease : Malnutrition, Acute Leukemia, Uncontrolled
diabetes, sickle cell anemia, Chronic alcoholism

61. CLASSIFICATION OF OSTEOMYELITIS

62.  It is a diffuse inflammation of soft tissues which tends to
spread through tissue spaces and along the facial planes
 Streptococci – hyaluronidase – destroys hyaluronic acid
 Prevotella and porphyromonas species destroy collagen
 It occurs as a sequela of an apical abscess or osteomyelitis or
periodontal infection.
 Other causes : infection following tooth extraction,
injection(infected needle or through infected area) or following
jaw fracture.
CELLULITIS

63.  Patient is moderately ill, elevated temperature and
leucocytosis
 Painful swelling of the soft tissues involved that are firm and
brawny.
 Involvement of superficial tissue spaces results in inflamed
skin with orange peel appearance.
 Regional lymphadenitis
CLINICAL FEATURES

64.  Maxilla – perforates outer cortical layer of bone above
buccinator attachment – swelling of upper half of the face.
 Extension towards eye may result in cavernous sinus
thrombosis
 Mandible – perforates outer cortical layer of bone below
buccinator attachment – swelling of lower half of the face.
 Extension to cervical area results in respiratory discomfort

65.  Administration of antibiotics including anti anaerobics
 Removal of cause of infection
 Patient is advised not to massage the area with any
medication
 Intravenous fluids to correct the dehydration.
 If it does not respond to conservative treatment, surgical
intervention is recommended.
TREATMENT

66.  Pericoronitis is inflammation of the soft tissue associated with
the crown of a partially erupted tooth.
 Most commonly seen in relation to the mandibular third
molar.
 Common symptoms and signs are pain, swelling, trismus,
halitosis, bad taste, inflammation of pericoronal flap and pus
discharge from underneath it.
PERICORONITIS

67.  Most common cause - entrapment of plaque and food debris
between crown of tooth and overlying gingival flap or
operculum.
 This is an ideal area for the growth of bacteria and It is
difficult to keep clean.
 Acute pericoronitis is characterized by a red, swollen,
suppurating lesion which is tender, with severe throbbing pain
radiating to the ear, throat, floor of the mouth,
temporomandibular joint and posterior submandibular region.

68.  Patient also complains of pain during swallowing (dysphagia),
halitosis, a foul taste and an inability to close the jaws.
 Chronic pericoronitis is characterized by a dull pain with
mild discomfort lasts for a day or two, with remission lasting
for many months.
 Patient may also complain of a bad taste.

69.  Acute phase - debridement of plaque and food debris, drainage
of pus, irrigation with sterile saline, chlorhexidine or hydrogen
peroxide, elimination of occlusal trauma and prophylactic
antibiotic along with analgesics.
 Surgical intervention will be made after acute phase
subsided.
 An extraction of partially or completely impacted third molar
should be done or operculectomy.
TREATMENT

70.  Sialadenitis is the inflammation of the salivary glands
 Causes range from simple infection to autoimmune etiologies.
 Sialadenitis is usually caused by bacterial or viral infection
 Other causes:
 Trauma
 Radiation and
 Allergic reaction
SIALADENITIS

71. CONCLUSION
 Without inflammation, infections would go unchecked.
wounds would never heal, and injured organs may remain as
permanent decaying lesions.
 In our day to day live we come across many cases starting
from gingivitis to oral cancer wherein inflammation exerts a
direct or indirect effect.
 So understanding inflammation helps us to know the
various vascular and cellular changes, mediators involved
and therefore help us to evaluate the significance of various
antibiotics and anti-inflammatory drugs that we do prescribe,
for controlling the same.

72. 1. Harsh mohan Textbook of pathology. 6th edition. Jaypee publication.
2. Kumar, abbas, aster Robbin’s textbook of pathology. 9th edition.
Elsevier publication.
3. Rajendran R, Sivapathasundharam B Shafer’s textbook of oral
pathology. 5th edition. Elsevier publication.
4. Newmann, Takei, Carranza textbook of clinical periodontology. 9th
edition. W.B. saunders company publication.
5. Color Atlas of Pathology Pathologic Principles · Associated
DiseaseUrsus-Nikolaus Riedes.
6. Fundamentals of Inflammation Charles N. Serhan.
REFERENCES