perio

1. INFLAMMATI
ON
Presented By-Malti Gaur
Guided By- Dr. Viniti goel
Presented To:
Dr. Viniti Goel ( Professor and Head)
Dr. Deepak Grover ( Professor )
Dr. Sarvani, Dr Vikram
Dr. Sonam

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

3. INTRODUCTIO
N
Inflammation
Inflammation is defined as the local response of living mammalian tissues to injury from
any agent. It is a body’s defence reaction in order to eliminate or limit the spread of
injurious agent, followed by removal of the necrosed cells and tissues
 Term inflammation is derived from Latin word ‘inflammare’ = ‘to burn’.
and eliminate
the
 Our Principal safeguard against injury
 Fundamentally designed to localize
causative agents & limit tissue injury.
– itis
 Majority of lesions are named by adding suffix
.

4. HISTOR
Y
 Egyptians first described in 3000 B.C
 Celsus (1st century AD) − 4 cardinal signs ofinflammation
Rubor ,Tumour, dolor & calor
 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.

6. CAUSES OF
INFLAMMATION
Exogenous Causes
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
Endogenous Causes
Immunologic disorders- hypersensitivity reactions,
autoimmunity,immunodeficiency states etc
Genetic/metabolic disorders-examples gout, diabetes mellitus etc.

7. 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.

8. CLASSIFICA
TION
 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.

9. 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

10. 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
EXUDATIONOF
LEUKOCYTES
PHAGOCYTOSIS

11. 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

12. 4. Slowing or stasis
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.

13. 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

14. B. ALTERED VASCULAR PERMEABILITY
STARLING’S HYPOTHESIS
 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.

15.  Normally whatever
little fluidIs left in the interstitial
Is drained by the lymphatics and thus no oedema results.
 In inflamedtissues, 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
compartm
ent

16. MECHANISMS OF INCREASED VASCULAR PERMEABILITY

17. II.CELLULAR
EVENTS
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.
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

18. 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

19. 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

20. 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:

21. 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

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

27. 4. CHEMOTAXIS
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 poresof filter towards the chemotactic agent.

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

29. 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:

30. RECOGNITIONANDATTACHMENTOFPARTICLE
ENGULFMENTWITHFORMATIONOFPHAGOCYTICVESICLE
KILLING & DEGRADATIONST
AGE

31. ENGULFMENT
1) Microbes recognised by receptor and bind to phagocytic receptor
2) Signals lead to membrane remodelling and change in cytoskeleton
3) Polymerisation of actin filaments
4) Extension of cytoplasm: Pseudopods
5) Extends to flow around microbe
6) Plasma membrane pinches off to form a vesicle (phagosome containing
microbe)
7) Fuses with lysosome – Phagolysosome

32. KILLING AND DEGRADATION
A) Killing of microbes is accomplished by reactive oxygen species (
ROS) and reactive nitrogen species mainly derived from nitric oxide (
NO)
B) The above mentioned along with lysosomal enzymes destroys
phagocytosed debris.
Killing of organism occurs through :
- Oxidative killing
- Non oxidative killing

33. Oxidative killing- also known as respiratory burst
Is mediated by:
NADPH ( nicotinamide adenine dinucleotide phosphate)
1. NADPH converts oxygen to reactive oxygen species ( hydrogen
peroxide and superoxide) that are lethal to microorganism .
2. NADPH combined with myeloperoxidase; HOCL
(HYPOCHLOROUS ION) are produced which are highly effective oxidant
and antimicrobial agents.
Non oxidative killing- This occurs due to release of bactericidal enzymes
into phagolysosomes.
- Each enzyme has distinct antimicrobial spectrum providing broad
coverage against bacteria and fungi.
- Enzymes- acid proteases-degrade bacteria.
neutral proteases-degrade extracellular
components.
anti- proteases-control harmful effect of proteases.

34. Neutrophils can extrude their nuclear
contents to form extracellular
NETs ( neutrophil extracellular traps)
-NETs traps – these are networks of
extracellular
fibres, primarily composed of DNA from
neutrophils, which bind
pathogen.
-Mechanism by which leukocyte damage
normal tissues are same as the
mechanism involved in antimicrobial
defence.

35. CHEMICAL MEDIATORS OFINFLAMMATION
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.

36. 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

37. 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.
• ThromboxaneA2
• Prostacyclin
LIPO – OXY– GENASE
PATHWAY
 5– HETE
 Leukotrienes

39. Neutrophils in Periodontal Inflammation; Periodontal Disease. Front Oral Biol.
Basel, Karger, 2012, vol 15, pp 56–83
GRANULES OF NEUTROPHILS:
• MPO
• ACID HYDROLASES
• ACID PHOSPHATASE
• PHOSPHOLIPASE
• PROTEASES
• COLLAGENASE
• ALKALINE PHOSPHATASE
• LACTOFERRIN
• LYSOZYME

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

41. CYTOKINES/CHEMOKINES
 proteins produced mainly by- activated
macrophages , also from endothelium,
lymphocytes &
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)

42. CYTOKINE CELLSOURCE MAIN ACTION
IL-1 Monocytes/macrophages. • Emigrationof neutrophils and macrophages
• Rolein fever and shock
IL-6 Monocytes/macrophages. • Hepatic production of acutephaseprotein
• Differentiation and growth of Tand Bcells
IL-8 Monocytes/macrophages,T
cells,neutrophils.
• Inducesmigrationof neutrophils, macrophagesandTcells
• Stimulates releaseof histaminefrom basophils
• Stimulates angiogenesis
TNF-α Monocytes/macrophages,
mast cells/basophils.
• Hepatic production of acute phaseprotein
• Systemic features(fever, shock,anorexia)
• Enhanced leucocytecytotoxicity
• Inductionof pro-inflammatory cytokines
IFN-g Tcells, NKcells Allcells • Activationof macrophagesand NKcells
• Stimulates secretion of Igs by Bcells
• Differentiationof Thelpercells
MCP-1 Fibroblasts, smoothmuscle
cells.
• Chemoattractant for monocytes,Tcells and NKcells
• Stimulates releaseof histaminefrom basophils
PF-4 Platelets, megakaryocytes
Fibroblasts, endothelial
cells
• Chemoattractant forfibroblasts
• Inhibitory to haematopoieticprecursorsand endothelial cell
proliferation
MAJOR CYTOKINES IN
INFLAMMATION

43. CHEMOKINES:
CHEMOKINES ARE A FAMILY OF SMALL PROTEINS THAT ACT
PRIMARILY AS CHEMOATTRACTANTS FOR SPECIFIC TYPE OF
LEUKOCYTES.
GROUP TYPE OFCHEMOKINE FUNCTION
C – X – C IL-8 Activation and
chemotaxis of
Neutrophils
C – C MCP-1 Attracts Monocytes,
Eotaxin eosinophil, basophils
MIP-1 and lymphocytes but
RANTES NOT Neutrophils
C Lympholactin Specific for
lymphocytes
C – X3 – C Fractalkine Chemoattractant for
monocytes and T cells

44. 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

45. 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

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

47. 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

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

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

50.  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

51. Role of Mediators in Different Reactions of Inflammation

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

53. 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.

54. 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.

55. 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.

56. 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.

57. 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.

58. 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.

59. PATHOGENESIS OF GRANULOMA.

60. RESOLUTION OF INFLAMMATION
It is an active process that results in a return to normal haemostasias,
and is mediated by specific molecules including a class of
endogenous lipid mediators, lipoxins, resolvins and protectins
.
• Lipoxins: LX A4, B4. They also signal macrophages to phagocytose
the remnants of apoptotic cells at sites of inflammation, without
generating an inflammatory response.
• Resolvins : They inhibit neutrophilic infiltration and transmigration,
they inhibit production of inflammatory mediators.
• Protectins: They reduce cytokine expression and also inhibit
neutrophilic infiltration.

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

62. 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

63. STAGES OF GINGIVITIS

64. 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

65.  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

66. 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
of rapid progression
 Subgingival calculus common finding
 Slow-moderate progression; periods
possible
 Modified by local factors/systemic factors/stress/smoking

67. EXTEN
T:
• 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

68. HISTOPATHOLOGY OF GINGIVITIS AND
PERIODONTITIS
Infiltration of the tissues by defense cells, neutrophils, macrophages, plasma
cells, and lymphocytes.
Accumulation of defense cells and the extracellular release of their
destructive enzymes
There is disruption of the normal anatomy of the connective tissues resulting
in collagen
depletion.
Vasodilatation and increased vascular permeability leads to increased leakage
of fluid out of the vessels, and
Facilitates the passage of defense cells from the vasculature into the tissues
which appear erythematous and edematous.

69.  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

70.  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.

71.  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.

72.  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

73. 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.

74. REFERENCES
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.