2. INTRODUCTION - History
General features of inflammation
2
Classification of inflammation
ACUTE INFLAMMATION – Stimuli
Vascular Events & Cellular Events
Morphology of acute inflammation
CHEMICAL MEDIATORS OF INFLAMMATION
CHRONIC INFLAMMATION – causes
features
DENTAL ASPECTS OF INFLAMMATION
DENTAL ABSCESS
3. 3
WOUND HEALING
Introduction
Regeneration & Repair
Healing by primary intention & secondary intention
Healing in oral tissues - Extraction socket
Re-implanted tooth
Alveolar bone
Newer concepts in healing
Factors affecting healing
4. INTRODUCTION
"A localised protective response
elicited by injury or destruction of
tissues , which serves to destroy ,
dilute or wall off both infective agent
and injured tissue.
According to ROBINS
INFLAMMATION is a complex reaction to
injurious agent such as microbes and damaged ,
necrotic cells that consist of vascular responses ,
migration , and activation of leukocytes and
systemic reaction
4
5. HISTORICAL HIGHLIGHTS
Egyptian Papyrus , 3000 BC CELSUS , Roman Writer
- 1 AD - CARDINAL SIGNS
JOHN HUNTER , 1793 –
“ Inflammation is not a disease
but a salutary effect on host”
JULIUS CONHEIM-1st used
microscope to observe inflamed
blood vessels & cells 5
6. 6
GIVEN BY CELSUS
• REDNESS
• SWELLING
• HEAT
• PAIN
Rubor
Tumor
Dolor
Calor
• LOSS OF FUNCTIONFUNCTIO
LAESA
BY VIRCHOW
8. ACUTE INFLAMMATION
An acute condition is one with a rapid onset and/or a short course
INFECTIONS :
Bacterial / viral /
parasitic & microbial
toxins
Trauma :
Blunt / penetrating
Physical /
chemical agents
eg thermal injury
Foreign body eg
sutures / splinters
Immune reactions /
hypersensitivity
reactions
8
9. ACUTE INFLAMMATION
Alteration in
vascular calibre/
HEMO-DYNAMIC
change
Structural
changes in micro-
vasculature
Emigration of
leukocytes &
accumulation in
focus of injury
9
13. PERSISTENT PROGRESSIVE VASODILATION
• 1st involves arteriole ………then other capillary bed
• seen in 1st 30 min.
• Results in Incr. blood vol. in microvascular bed
• By mediators
- Nitric oxide (NO)
- Histamine
13
14. 14
INCREASED PERMEABILITY OF
MICROVASULATURE
• Contraction of endothelial cells - Histamine
• Retraction of endothelial cells – cytokine IL – 1 , TNF
• Direct injury to endothelial cells
• Endothelial injury mediated by leukocytes
• Leakage from new blood vessels
15. STASIS
Increased vascular permeability leads
to loss of fluid from microvasculature
Concentration of red cells in small
vessels
Slower blood flow
S
T
A
S
I
S
15
16. LEUCOCYTIC MIGRATION & EMIGRATION
Stasis is followed by peripheral orientation
of leucocytes along vascular endothelium
Movement of leucocytes in extracellular
space through gaps b/w endothelium.
16
20. CELLULAR EVENTS
Deliver leukocytes to site of
injury
To perform their ‘FUNCTION’
Ingest offending bacteria
Kill bacteria & other microbes
Get rid of necrotic tissue & foreign
substance
20
21. CELLULAR EVENTS
• Margination
• Rolling
• Adhesion
IN THE LUMEN
TRANS-
MIGRATION
• Migration into
interstitial tissue
EMIGRATION
CHEMOTAXIS
PHAGOCYTOSIS
21
23. • Margination
• Rolling
• Adhesion
IN THE LUMEN
CELLULAR EVENTS
Leukocytes now tumble along the endothelium
Have a TRANSIENT adhesion with endothelium
23
29. EXOGENOUS
SUBSTANCES
ENDOGENOUS
SUBSTANCES
Bacterial Products :
a) Peptides – N – formyl
methionine terminal amino
acid
b) Lipids
a) LTB-4
b) PF-4
c) Components of
complement system
d) Cytokine :
IL – 1, 5 , 6
e) Monocyte
chemoattractant
protein
f) Chemotactic factor
for CD-4 cells
g) Eotaxin chemotactic
factor for eosinophils
CELLULAR EVENTS
29
30. 6 to 24 hours 24 to 48 hours
CELLULAR EVENTS
30
In chemotaxis…..
42. 42
filters the extravascular fluids
in inflammation…. lymph flow is inc. and helps drain the edema fluid
from extravascular space
LYMPHATICS
LYMPHANGITIS
DRAINING LYMPH NODES
LYMPHADENITIS
43. ‘ MEDIATOR ‘ : one that reconciles differences b/w disputants
CHEMICAL MEDIATORS : chemical substances that mediate the
process of inflammation………..
43
44. CHEMICAL MEDIATORS OF INFLAMMATION
Present in plasma in
precursor form
Must be activated to
acquire biologic properties
Pr. In intracellular granules
Major cellular sources
Platelets
Neutrophil
Monocyte / macrophage
44
45. CHEMICAL MEDIATORS OF INFLAMMATION
VASO – ACTIVE AMINES
45
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
eg substance P
Cytokines IL – 1 , 8
SEROTONIN
SOURCE : 1) Platelets
2) Enterochromaffin cells
STIMULI : Platelet aggregation after
contact with collagen ,
thrombin
49. CHEMICAL MEDIATORS OF INFLAMMATION
CYTOKINES
• proteins produced mainly by- activated lymphocytes & macrophages , also
from endothelium, epithelium & connective tissue cells.
TNF and IL - 1
• major cytokines that mediate inflammation.
• Produced mainly by activated macrophages
STIMULI :
• Immune reactions,
• physical injury & variety of inflammatory stimuli.
• endotoxins & other microbial products
49
50. NITROUS OXIDE
CHEMICAL MEDIATORS OF INFLAMMATION
Released by activated neutrophils and macrophages
Superoxide , hydrogen peroxide , hydroxl ion
ACTION : Endothelial cell damage- inc. vascular permeability
Damage to cells and tissue matrix by activating protease and inactivating
anti-protease
50
6 OXYGEN METABOLITES
mediates in vascular dilation
54. FATE OF ACUTE INFLAMMATION
ACUTE
INFLAMMATION
RESOLUTION
HEALING BY
SCARRING
PROGRESSION TO
SUPPURATION
PROGRESSION TO
CHRONIC
INFLAMMATION
54
55. CHRONIC INFLAMMATION
Inflammation of prolonged duration (weeks to months) in which
inflammation , tissue destruction and attempts at repair are proceeding
simultaneously.
CAUSES
Following acute inflammation
Begin insidiously as a low – grade inflammation
Persistent inf. By micro-organisms : tubercle bacilli ,
Prolonged exposure to toxic agents
Auto - immunity
55
56. FEATURES OF CHRONIC INFLAMMATION :
56
CHRONIC
INFLAMMATION
Infiltration with mononuclear cells
– macrophages ,lymphocytes , &
plasma cells
Tissue
destruction
Healing by Proliferation &
connective tissue replacement of
damaged tissue
58. • Incr. lysosomal enzymes
• Greater ability to
phagocytose 58
ACTIVATION OF MACROPHAGE
Cytokine
IFN - ɤ
Endotoxin ,
fibronectin
chemical
mediators
59. MACROPHAGE
IN ACUTE
INFLAMMATION
IN CHRONIC
INFLAMMATION
* Irritant eliminated –
macrophage
disappears
Persistent macrophage accumulation by following
mechanisms :
1. )Recruitment from circulation – Chemotactic
stimuli include :
a) C5a
b) Platelet derived growth factor
c) Transforming growth factor
2.) Local proliferation of macrophages
3.) Immobilization of macrophages
59
65. REACTIONS OF PULP TO BACTERIAL INVASION
ᶲ Vascular changes take place inside
blood vessels.
ᶲ PMNLs reach the area of
inflammation
ANATOMICAL FEATURES OF PULP THAT TEND
TO ALTER THE RESPONSE
Enclosure of pulp in rigid calcified walls - PREVENTS EXCESSIVE
SWELLING …thus more painful.
Pressure leads to decr. Blood supply and ischaemia – does not get
corrected since collateral circulation cannot develop through tiny apical
foramina
65
66. HISTOLOGIC FEATURES OF PULPITIS
ACUTE CHRONIC
66
MONONUCLEAR CELLS
PREDOMINATE - chiefly
plasma cells & lymphocytes.
Fibroblastic activity is
evident
collagen fibres seen in
bundles
• Continued vascular dilation
• Accumulation of oedemal
fluid in connective tissue
• Pavementing Of PMNLs
along endothelial wall
• Through quiescence
of acute pulpitis
• Begin as chronic d/s
from onset
68. UNTREATED PULPITIS
• Inflammation of periodontal ligament around root apex..
Changes localised around root
apex…..since richly vascular Resorption of bone – ABSCESS
FORMATION
68
69. 69
PYOGENIC ABSCESS PYAEMIC ABSCESS COLD ABSCESS
• Commonest type
• mostly found in soft
tissues
• eg periapical abscess
• occurs due to
circulating bacterial
emboli in blood
Abscess without signs
of inflammation
Eg Tubercular abscess
70. ABSCESS FORMATION / SUPPURATION
Acute bacterial inf. + intense neutrophillic infiltrate
TISSUE NECROSIS
Cavity is formed called an ABSCESS
Contain purulent exudate called as PUS
70
71. MICRO-ABSCESS
Rise in pressure with inflammatory
exudate
Local tissue hypoxia
Localised destruction ….breakdown of
leucocytes , bacteria & tissue
ABSCESS FORMATION
PERIAPICAL ABSCESS
71
76. 76
WOUND : Anatomic or functional interruption in continuity of a tissue
that is accompanied by cellular damage and death
INTRODUCTION
MAY BE INFLICTED BY :
Physical injury Chemical injury Biologic injury
Series of co-ordinated processes directed towards restoring the injured
tissue of body to as near normal as possible is termed as WOUND
HEALING
77. 77
GOAL
a.) to restore continuity b/w wound edges
b.) To re-establish tissue function
REGENERATION
REPAIR
Biologic process by which
both structure and function
of disrupted or lost tissue is
completely restored.
Biologic process whereby
continuity of disrupted or
lost tissue is regained by
new tissue which does
not restore structure &
function
78. 78
REGENERATION
• Healing by proliferation of parenchymal
cells,
• results in complete restoration of the
original tissues
Cell growth
Cell
differentiation
Cell-matrix
interaction
GROWTH FACTORS
1. Epidermal
2. Fibroblast
3. Platelet derived
4. Endothelial
5. Transforming
79. 79
REPAIR
Healing by conn. Tissue Fibrosis and scarring
Phase of inflammation
Phase of clearance
Phase of ingrowth of granulation tissue
81. 81
HEALING BY PRIMARY INTENTION / FIRST
INTENTION
Conditions:
• Clean and uninfected wounds
• Surgically incised
• Edges are Approximated
• Without much loss of tissue
85. 85
Basal cells from both cut margins start proliferating and
migrating towards incisional space in form of epithelial
SPURS
A well approximated wound is covered by layer of
epithelium in 48 hrs
By 5th day a multilayered new epidermis is
formed.
PROLIFERATIVE PHASE – involves epithelial changes
86. 86
Organisation starts by 3rd day
5th day : new collagen fibrils start forming
which dominate till healing is complete
In 4 weeks Scar tissue formed
• Scanty cellular and vascular elements
• few inflammatory cells
REMODELLING PHASE – involves ORGANISATION
87. 87
CONDITIONS:
Open wound with a large tissue defect
Having extensive loss of cells and tissue
Wound is not approximated by sutures
HEALING BY SECONDARY INTENTION
90. 90
MOIST ENVIRONMENT
UNUSUAL ANATOMIC SITUATION
COUNTLESS MICROORGANISMS
MARKED CAPACITY FOR REGENERATION
EASY REMODELLING OF SCAR TISSUE
fibroblasts in oral mucosa are phenotypically different from those of skin & more
closely resemble fetal fibroblasts .
91. 91
HEALING OF EXTRACTION SOCKET
Consists of erythrocytes &
leucocytes in mesh of fibrin
STAGE 1 : coagulation
STAGE 2 : Granulation tissue
STAGE 3 : Connective Tissue
collagen & reticuloendoth.
fibres
STAGE 4 : Bone Development
Begins at 7th post op day
By 40th day socket almost
completely filled with WOVEN
bone
STAGE 5 : Epithelial Repair
Begins at 4th post op day ;
completes by 24th day
92. 92
FIBROUS UNION
• Occurs when tooth xtn accompanied with both buccal and lingual
periosteum loss.
• RADIOGRAPHIC FEATURES : well circumscribed radiolucent area in site of
previous xtn
May be mistaken for residual infection
• HISTOLOGIC FEATURES : dense bundles of collagen with occasional
fibrocytes and few blood vessels
• TREATMENT : excision of wound may ……..
93. 93
DRY SOCKET
• Most common and painful complication
• Occurs due to disintegration / loss of blood
clot
• CLINICAL F :
• Foul odour
• Severe throbbing type of pain
TREATMENT
• AIM : to keep socket clean
to protect exposed bone
• Irrigation with mild warm antiseptic
Palliative socket dressing of ZOE – iodoform gauze
94. 94
HEALING OF RE-IMPLANTED TOOTH
oCLOT b/w root n ruptured PDL
oFIBROBLAST PROLIFERATION on pdl remnants on bone side
oRECONNECTION – occurs by collagen fibres extending from
cementum to alveolar bone
oREATTACHMENT OF EPITHELIUM – by 7th day
o2-4 weeks - complete regeneration of pdl
97. 97
Pulp is highly specialised loose connective tissue with specific response to
surgical and traumatic injuries and bacterial insult
PREDOMINANT CELL TYPES IN PULPAL REPAIR
Fibroblasts - present uniformly throughout pulp
Undifferentiated mesenchymal cells – located paravascularly
PULPAL VASCULATURE in healing :
Within pulp…esp apically.. ARTERIO-VENOUS shunts are present
Control the tissue pressure during inflammation
When tissue pressure exceeds that of venules , a
decrease in blood flow results
98. 98
2 BASIC RESPONSE DETERMINING HEALING OF PULP
PULPAL WOUND
HEALING RESPONSE
DEFENSE
RESPONSE
Damaged pulp tissue is
healed by replacement
with newly differentiated
tissue
Aims at neutralising or
controlling bacterial
invasion
Depends upon type of progenitor
cells involved
Eg. PDL derived progenitor cells – cementum
deposition along RC walls
Patent apical foramen - Sharpeys fibre
insertion
Involves creating barrier
against micro – org. by
• granulation tissue
• hard tissue – secondary
dentin / cementum
100. 100
FACTORS INFLUENCING WOUND HEALING
SYSTEMIC
FACTORS
AGE
NUTRITIONAL DEFICIENCIES
BLOOD DYSCRASIAS
• Vitamin C , E , A
• Proteins
101. 101
Healing of chronic wound can be enhanced by one of the following methods
1. Topical application of growth factors.
2. Hyperbaric oxygen therapy.
Systemic
Local.
3. Electrical stimulation for wound healing
Direct current
Low frequency pulsed current (LFPC)
High voltage pulsed current (HVPC)
4. Topical application of cultured keratinocytes.
5. Vacuum assisted closure of the wound.
103. Refrences……..
103
1) Robbin’s & Cotron Pathological basis of diseases -7th edn.
2) Essential pathology for dental students –Harsh mohan,3rd edn.
3) Text book of oral pathology – Shafer 4th edn.
4) Textbook and colour atlas of traumatic injuries to the teeth—
J.O.Andreasen, F.M.Andreasen 3rd edn.
5) Google search
Although clin f. of inflamm were describd in an egyptian papyrus 3000 BC , Celsus ..a roman writer 1st listed cardinal signs of inflammation
1793 – john Hunter a Scottish surgeon niticed that …..
Julius Conheim……
The five cardinal signs of acute inflammation - "PRISH"
An ingrown toenail with the five PRISH signs; pain, redness, immobility, swelling and heat
Pain - the inflamed area is likely to be painful, especially when touched. Chemicals that stimulate nerve endings are released, making the area much more sensitive.
Redness - this is because the capillaries are filled up with more blood than usual
Immobility - there may be some loss of function
Swelling - caused by an accumulation of fluid
Heat - as with the reason for the redness, more blood in the affected area makes it feel hot to the touch.
The five classical signs of inflammation
Although Latin terms are still used widely in Western medicine, local language terms, such as English, are taking over. PRISH is a more modern acronym which refers to the signs of inflammation. The traditional Latin based terms have been around for two thousand years:
Dolor - Latin term for "pain"
Calor - Latin term for "heat"
Rubor - which in Latin means "redness"
Tumor - a Latin term for "swelling"
Functio laesa - which in Latin means "injured function", which can also mean loss of function.
These changes begin early after injury and develop at varying rates depending upon severity of injury.
There are no free lunches in this world and the price for this defence by leukocytes is that some normal tissue damage also takes place.
Normal blood flow consists of a central stream of cells – compr of leukocytes & RBCs & plasma occupies periphery
Due to slowing of blood flow & stasis taking place during inflammation ; central zone widens & plasma zone narrows since plasma is lost during exudation
As a result of this , neutrophils in central column now come close to vessel wall
This is MARGINATION
(In the end) : this process is rolling.
As said earlier.rolling is a form of transient adhesion.
after rolling & transient adhesion , leukocytes come to rest at and adhere firmly
in some time , endothelium gets lined by WBCs giving appearance of pavementing / pebbles over which stream runs without disturbing
Leukocytes thus escape thru these defects….this process is emigration.
Chemicals that cause movement of bacteria are called CHEMO-ATTRACTANTS
But to establish a bond b/w bacteria and cell membrane of phagocytic cell …micro-org get coated with opsonins.
Now , there should be receptors on leukocyte surface also to recognise these opsonins.these include
NOW, we have discussed the histologic aspects of inflammation…but in day to day clinical experience we cant observe the histology…so what we observe is the morphology…..
1. One that mediates, especially one that reconciles differences between disputants.
2. Physiology A substance or structure that mediates a specificresponse in a bodily tissue.
Aftr ………… “ although injury starts the inflammatory response , these chemical factors bring about various vascular & cellular changes. “
Role :
dil. Of arterioles
incr permeability of vasculature
Proliferation of small blood vessels (ANGIOGENESIS)
Fibrosis
Mononuclear cells arise from precursors in bone marrow … which give rise to blood monocytes…monocytes then start emigrating into extravascular tissue i.e out of blood and reach various tissuesand form predominant cell type in 48hrs of inflamm.
When monocyte reaches extravascular tissue..it transforms to form macrophages.
Blood monocytes on reaching extravascular space get transformed into macrophages.
Like other tissue throughout the body , pulp reacts to bact. Infection or other stimuli thru inflamm process k/a PULPITIS
Will be discussed in comparison to injury due to sharp object on skin.
Loss of collateral circulation ….also another reason why analgesics become ineffective in relieving pain of pulpal origin.
Consists of
Vascular changes , infiltration of PMNLs , and exudate accumulation
Periapical abscess formn is not a sudden and rapid process…..begins with formation of micro abscess
After microabscess……this process keeps progressing towards remaining pulp..until reaches apex and causes apical p.dtis & periapical abscess.
PRESENTS WITH…features of…
“ BOX”
Chronic per abscess – mild well circumscr area of suppuration that shows little tendancy to spread.
BLIND TRACT leading from surface and down to tissues
Lined by GRANULATION TISSUE
Now this restoration of body tissues is brought about by two methods :
Regeneration & Repair.
After def of repair.” now the term ‘ does not’ is not very correct here.tissues after repair are definitely inferior to normal but restore func to some extent.
1st intention – occurs when a sharply made wound is accurately reapproximated within hours of injury
2nd int – filling a tissue defect by formation of new c.t – seen after avulsion injury
3rd int – occurs when wound is surgically closed after secondary healing has begun or when tissue grafts used to assist in healing.
Inflammation involves neutrophils and monocytes
Clearance involves proteolytic enzymes from neutrophils , autocatalytic enz from dead tissues & phagocytic activity of macrophages.
Read steps from andersen…pg 103.
After extraction, the defect is immediately filled with blood clot (hemostatic response)
The epithelial cells bordering the socket begin to proliferate & migrate across the clot so that after about 10 days the socket is epithelized
With the clot the inflammatory response takes place, first involving neutrophils then macrophages.
The proliferative & synthesizing phase differs from that in skin as the cells invading the clot are not fibroblasts but cells from the adjacent bone marrow that have osteogenic potential.
In clot they begin to form bone
Bone formation- 10 days it starts, by 10 – 12 weeks the extraction site can no longer be distinguished
Condition called as ‘dry’ b’coz after loss of clot..socket gives a dry appearance with b’coz of exposed bone.
Vitamin C deficiency:
Results in capillary fragility
Formation of unstable collagen which is quickly
degraded by collagenolysis.
Vitamin E:
Serves as membrane stabilizer & plays an important
role in lysosome function
Vitamin A deficiency:
Decrease collagen synthesis and stability
