Pathology

1. INFLAMMATION
AND
HEALING
Seminar by:
RUHEENA KHAN
PG 1st year
DEPARTMENT OF ORAL
MEDICINE AND RADIOLOGY

2. INFLAMMATION
INTRODUCTION
TYPES
ACUTE INFLAMMATION
CHEMICAL MEDIATORS OF INFLAMMATION
CHRONIC INFLAMMATION
DENTAL ASPECTS OF INFLAMMATION

3. DEFINITION:
Inflammation is defined as the local response of living tissues to
injury due to any agent.
ETIOLOGY:
The causes of inflammation are many and varied:
 Exogenous causes:
 Physical agents
 Mechanic agents: fractures, foreign corps, sand, etc.
 Thermal agents: burns, freezing
 Chemical agents: toxic gases, acids, bases
 Biological agents: bacteria, viruses, parasites
 Endogenous causes:
 Circulation disorders: thrombosis, infarction, hemorrhage
 Enzymes activation – e.g. acute pancreatitis
 Metabolic products – uric acid, urea

4. CELSUS in 1st century A.D named the famous 4 cardinal signs
of inflammation as:
 rubor (redness)
 tumor (swelling)
 calor (heat)
 dolor (pain)
To these, 5th sign functio laesa, or loss of function was later
added by VIRCHOW
SIGNS OF INFLAMMATION

5. TYPES OF INFLAMMATION
ACUTE
Rapid onset
Short duration
Fluid accumulation, plasma protein exudation
Neutrophils
CHRONIC
Onset- insidious
Longer duration
Lymphocytes, macrophages, plasma cells as inflammatory
cells

6. ACUTE INFLAMMATION
VASCULAR EVENTS CELLULAR EVENTS
1. HAEMODYNAMIC CHANGES
2. ALTERED VASCULAR PERMEABILITY
1. EXUDATION OF LEUKOCYTES
2. PHAGOCYTOSIS

7. VASCULAR EVENTS
1. 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

8. 4. Slowing or stasis
Increased vascular permeability
Increased concentration of RBCs
Raised blood viscosity
Slower blood flow

9. slowing followed by
LEUCOYTE MIGRATION (neutrophils mainly) to the
vascular endothelium
Leukocytes then move and migrate
through gaps between the endothelial
cells in the extravascular space.
EMIGRATION

10. 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

11. STARLING’S HYPOTHESIS
2. 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.

12. Normally whatever little fluid is left in the interstitial compartment
is drained by the lymphatics and thus no oedema results.

13.  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. 1. Endothelial cell contraction
reversible process
mediated by histamine, bradykinin, leukotrienes
short duration: 15-30 min.
2. Retraction of EC
TNF and IL-1
onset of response takes 4-6 hrs after injury and lasts for 2-4
hours or more

16. 3. Endothelial injury
immediate sustained response,
lasts for several hours or days
4. Leukocyte-mediated endothelial injury
activation of leucocytes release proteolytic enzymes and toxic
oxygen species.
Late response
5. Neovascularisation
under the influence of VASCULAR ENDOTHELIAL GROWTH
FACTOR during the process of repair are leaky

17. MECHANISM
MICROVAS-
CULATURE
RESPONSE
TYPE
PATHOGENESIS
EXAMPLES
CELL
CONTRACTION
Venules Immediate
15-30 min
Histamine
Bradykinin
Mild thermal
injury
CELL
RETRACTION
Venules Delayed 24
hrs or more
IL-1, TNF In vitro only
DIRECT CELL
INJURY
Arterioles
Venules
Capillaries
Immediate or
delayed
Cell necrosis
and detachment
severe Burns,
Bacterial
infections,
radiation injury
LEUCOCYTE-
MEDIATED
Venules
Capillaries
Delayed Leucocyte
activation
Pulmonary
venules
NEOVASCULARI
SATION
All Any type VEGF tumours

18. CELLULAR EVENTS
1. 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.

19. CHANGES LEADING TO MIGRATION
1. CHANGES IN THE FORMED ELEMENTS OF BLOOD
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

21. 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

22. ADHESION MOLECULES:
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 SUPER FAMILY ADHESION
MOLECULE: ICAM-1,2

23. 3. EMIGRATION

24. 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

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

26. 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.

27. 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.

28. AGENTS ACTING AS CHEMOTACTIC SUBSTANCES
EXOGENOUS SUBSTANCES ENDOGENOUS SUBSTANCES
a) Peptides – N –
formyl methionine
terminal amino
acid
b) Lipids
a) LT-B4
b) PF-4
c) Components of
complement system
c3,c5
d) Cytokine :
IL – 1, 5 , 6
e) Monocyte
chemoattractant
protein
f) Chemotactic factor for
CD-4 cells
g) Eotaxin chemotactic
factor for eosinophils

29. 2. 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 4 steps:

30. 4 STEPS:
RECOGNITION AND ATTACHMENT OF
PARTICLE
ENGULFMENT WITH FORMATION OF
PHAGOCYTIC VESICLE
DEGRANULATION STAGE
KILLING & DEGRADATION STAGE

32. Opsonins are naturally occuring factors in the serum.
1. IgG opsonin: Fc fragment of immunoglobulin G. It is naturally
occuring antibody in the serum that coats the bacteria while PMNs
possess receptors for the same.
2. C3b opsonin: fragment of complement. It is generated by the
activation of complement pathway.
3. Lectins: carbohydrate binding proteins in the plasma which bind
to the bacterial cell wall.

33. The opsonised particle is ready to be engulfed.
formation of cytoplasmic pseudopods around the particle
enveloping in the phagocytic vacuole
Eventually, the plasma membrane breaks from the cell surface and
the lysosomes of the cell fuse with the phagocytic vacuole
PHAGOLYSOSOME or PHAGOSOME

35. Preformed granule stored products of PMNs are released
into phagolysosome.
Mononuclear phagocyte also secrete enzymes eg
• IL-2 and 6,, TNF
• Arachidonic acid metabolites (Prostaglandins ,
leukotrienes , platelet activating factor)
• Oxygen metabolites (superoxide oxygen, hydrogen
peroxide, hypochlorous acid)
DEGRANULATION STAGE

36. KILLING OR DEGRADATION STAGE
The micro-organisms after being killed are degraded by hydrolytic
enzymes.
The antimicrobial agents act by 2 mechanisms:
OXYGEN - DEPENDENT BACTERICIDAL MECHANISM
OXYGEN - INDEPENDENT MECHANISM

37. OXYGEN DEPENDENT BACTERICIDAL
MECHANISM
An important mechanism of microbicidal killing is by production of
reactive metabolites
(O2, H2O2, HOCl, HOI, HOBr)
This type of activity is carried out either through enzyme
MYELOPEROXIDASE (MPO) present in the granules of
neutrophils and monocytes, or independent of enzyme MPO.

38. MPO – DEPENDENT KILLING MPO – INDEPENDENT KILLING
H202 HOCl,
Cl, Br, I
HOBr, HOI
+ H2O
MORE POTENT ANTIBACTERIAL AGENT
MPO
H2O2
O2
Fe++
HYDROXYL
RADICALS

39. Few agents released from the granules of phagocytic cells do not
require oxygen. These include:
 Lysosomal hydrolases
 Permeability increasing factors
 Defensins
 Cationic proteins
OXYGEN INDEPENDENT BACTERICIDAL
MECHANISM

40. 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.
Classified into 2 groups:
Mediators released by CELLS
Mediators originating from PLASMA

41. 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
VASOACTIVE AMINES

42. 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 METABOLITESLipo-oxygenase Pathway
Cyclo-oxygenase pathway
CYCLO – OXY- GENASE
PATHWAY
Prostaglandin - PGD2 , E2 ,
F2
Thromboxane A2
Prostacyclin
LIPO – OXY – GENASE
PATHWAY
5 – HETE
Leukotrienes
ARACHIDONIC ACID METABOLITES

43. Action:
Cyclooxygenase Pathway
• PGD2, PGE2, PGF2α
Vasodilatation
Potentiates Edema formation
• PGI2 (prostacyclin)
Vasodilatation, Inhibits Platelet aggregation
• TxA2
Vasoconstriction & stimulates platelets aggregation
Lipoxygenase Pathway
Vasoconstriction
Bronchoconstriction
Increased vascular permeability

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

45. 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
• Immune reactions,
• physical injury & variety of inflammatory stimuli.
• endotoxins & other microbial products
STIMULI
CYTOKINES

46. • TNF & IL-1
– Endothelial effects
• Endothelial activation
• WBC binding & recruitment
• Procoagulant activity
– Fibroblast effects
• Activates tissue fibroblasts
• Increases proliferation
• Production of collagen & ECM

47. mediates in vascular dilation
Anti-platelet activating agent
Possibly microbicidal action
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.
NITRIC OXIDE
OXYGEN METABOLITES

48. CLOTTING
SYSTEM
KININ
SYSTEM
COMPLEMENT
SYSTEM
FIBRINOLYTIC
SYSTEM

49. FACTOR XII
contact
FACTOR XIIa
FIBRINOLYTIC CLOTTING KININ
PLASMIN FIBRIN BRADYKININ
FIBRIN SPLIT PRODUCTS
COMPLEMENT SYSTEM
Permeability factors C3a, C4a, C5a

50. ANAPHYLOTOXINS :
1. Release of histamine from mast cells and basophils
2. Increased vascular permeability causing odema in
tissues
3. Phagocytosis
4. Chemotactic agent

51. FATE OF ACUTE INFLAMMATION
ACUTE
INFLAMMATION
RESOLUTION
HEALING BY
SCARRING
PROGRESSION
TO
SUPPURATION
PROGRESSION
TO CHRONIC
INFLAMMATION

52. CHRONIC INFLAMMATION
It is a prolonged process in which tissue destruction and
inflammation occurs at the same time.
Time course:
 > 48 hours (weeks, months, years)
 Cell type
 Mononuclear cells (Macrophages, Lymphocytes, Plasma cells)
Can be caused by 1 of the following 3 ways:
1. Chronic inflammation following acute inflammation
2. Recurrent attacks of acute inflammation
3. Chronic inflammation starting de novo

53. FEATURES OF CHRONIC INFLAMMATION
 Infiltration with mononuclear
cells – macrophages,
lymphocytes & plasma cells
CHRONIC
INFLAMMATION
Tissue
destruction
Healing by Proliferation &
connective tissue replacement of
damaged tissue

54. INFILTRATION WITH MONO-NUCLEAR CELLS

55. • Incr. lysosomal enzymes
• Greater ability to
phagocytose
55
ACTIVATION OF MACROPHAGE
Cytokine
IFN - ɤ
Endotoxin ,
fibronectin
chemical mediators

56. 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
56

57. 57
TISSUE DESTRUCTION OR NECROSIS
• ACTIVATED
MACROPHAGES
Elastase
Protease
Collagenase
Reactive oxygen
radical
Cytokine IL-1,8

58. 58
PROLIFERATION
Small BLOOD
VESSELS
FIBROBLAST
Resulting in the formation of granulation tissue

59. 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 decrease Blood supply and Ischaemia – does not get
corrected since collateral circulation cannot develop through tiny apical
foramina
59

60. HISTOLOGIC FEATURES OF PULPITIS
ACUTE CHRONIC
60
 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

61. • Inflammation of periodontal ligament around root apex..
Changes localised around root
apex…..since richly vascular.
Vascular changes , infiltration of
PMNLs , and exudate
accumulation
Resorption of bone –
ABSCESS FORMATION
61

62. WOUND HEALING

63. WOUND HEALING
INTRODUCTION
REGENERATION AND REPAIR
HEALING BY PRIMARY AND SECONDARY
INTENTION
FACTORS AFFECTING HEALING
HEALING IN ORAL TISSUES

64. WOUND:
A circumscribed injury which is caused by external force
and it can involve any tissue and organ.
It can be classified based on:
Origin of the wound.
Contamination of the wound.
Depth of the wound.

65. BASED ON ORIGIN
Mechanical
1. Abraded wound
2. Punctured wound
3. Incised wound
4. Cut wound
5. Crushed wound
6. Torn wound
7. Bite wound
8. Shot wound
Chemical
Acid & base
Radiation
Thermal
Burning & freezing
Special
Toxins & venoms

66. BASED ON CONTAMINATION
1. Clean wound
2. Clean & contaminated wound
3. Contaminated wound

67. BASED ON THE DEPTH
1. Superficial wound = only epidermis.
2. Partial thickness wound = epidermis + dermis.
3. Full thickness wound= epidermis + dermis +
subcutaneous fats
4. Deep wound = epidermis + dermis +
subcutaneous fats + exposed muscles, bone connective
tissue, organs etc.

68. HEALING
Healing is the body’s response to injury in an
attempt to restore normal structure and
function.
The process of healing involves 2 distinct processes:
a. REGENERATION
b. REPAIR

69. REGENERATION
 Regeneration : Is when healing takes place by
proliferation of parenchymal cells and usually
results in complete restoration of the original
tissues.
 To maintain proper structure of tissues, these cells
are under constant regulatory control of the cell
cycle.

70. REPAIR
 Is when healing takes place by proliferation of connective
tissue elements resulting in fibrosis and scarring.
 Two processes are involved in repair:
a. Granulation tissue formation
b. Contraction of wound
Cells involved in the process of repair;
1. Mesenchymal cells
2. Endothelial cells
3. Macrophages
4. Platelets
5. Parenchymal cells of injured organs

71. GRANULATION TISSUE
PHASE OF INFLAMMATION
Following injury blood clots at the site of injury.There is acute
inflammatory response with exudation of plasma, neutrophils,
and some monocytes within 24 hours.
PHASE OF CLEARANCE
Proteolytic enzymes liberated from neutophils, autolytic enzymes
from dead tissue and phagocytic activity of macrophages, clear
off the necrotic tissue, debris and red blood cells.
PHASE OF GROWTH OF GRANULATION TISSUE
This phase consists of two main processes
a. ANGIOGENESIS OR NEOVASCULARISATION
b. FIBROGENESIS

72.  ANGIOGENESIS ( NEOVASCULARISATION)
 Formation of new blood vessels at the site of injury takes place
by proliferation of endothelial cells from the margins of severed
blood vessels.
 The newly formed blood vessels are more leaky accounting for
the more edematous appearance of new granulation tissue.
 Soon these blood vessels differentiate into muscular arterioles,
thin-walled venules and true capillaries.
Angiogenesis takes place under the influence of :
1. Vascular endothelial growth factor
2. Platelet derived growth factor
3. Transforming growth factor- β
4. Fibroblast growth factor

73. FIBROGENESIS
 The newly formed blood vessels are present in an
amorphous ground substance. The new fibroblasts
originate from the fibrocytes as well as by mitotic
division of fibroblasts.
 Some of these fibroblast has functional and structural
similarities to smooth muscles cell called as
myofibroblast.
 Collagen fibrils appear by about 6th day. As maturation
proceeds, more and more of collagen is formed the
number of active fibroblasts and the number of new
blood vessels decreases.
 This result in the formation of inactive looking scar
known as cicatrisation.

74. GRANULATION TISSUE

75. CONTRACTION OF WOUND
 The wound starts contracting after 2-3 days and the process is
completed by 14th day. During this period the wound is reduced
by approximately 80% of its original size.
 Contraction of wound helps in rapid healing.
Factors responsible for wound contraction:
1. Dehydration due to removal of fluids by drying.
2. Contraction of collagen
3. Discovery of myofibroblasts.

76. TYPES OF WOUND HEALING
 HEALING BY FIRST INTENTION also called as
PRIMARY UNION.
 HEALING BY SECOND INTENTION also called as
SECONDARY HEALING.

77. HEALING BY FIRST INTENTION
Healing of wound with following characteristics:
 Clean and uninfected
 Surgically incised
 Without much loss of cells and tissue
 Edges of wound are approximated by surgical sutures.

78. STEPS IN PRIMARY WOUND HEALING
 INITIAL HEMORRHAGE: Immediately after injury, the space
between the surfaces of incised wound is filled with blood which
soon clots, and prevent further infection.
 ACUTE INFLAMMATORY RESPONSE: This occurs within 24
hours of appearance of polymorphs from the margins of incision.
 EPITHELIAL CHANGES: The basal cells of epidermis from
both cut margins starts proliferating and migrating towards
incisional space in the form of epithelial spurs.
 A well approximated wound is covered by a layer of epithelial cell
in 48 hrs. The migrated epithelial cell separates the necrotic cells
and clot forming a scab which cast off. The basal cells continues to
divide. By 5th day new epidermis is formed.

79.  ORGANISATION : by 3rd day, fibroblasts also invades the
wound area. By 5th day new collagen fibrils start forming
which dominate till healing is completed.
In 4 weeks a scar tissue with scanty cellular and vascular
elements, a few inflammatory cells and epithelialised surface
is formed.

80. HEALING BY SECONDARY INTENTION
This is defined as the healing of a wound with following features.
i. Open with large tissue defects, at times infected
ii. Having extensive loss of cells and tissues, and
iii. The wound is not approximated by sutures but is left open.
STEPS IN HEALING OF SECONDARY WOUND:
 Initial haemorrhage: as a result of injury the wound space is
filled with blood and fibrin clot which dries.
 Inflammatory phase: there is initial acute inflammatory
response followed by appearance of macrophages which clear
off the debris.

81.  EPITHELIAL CHANGES: The epidermal cells from both the
margins proliferate and migrate into the wound in the form of spurs
till they meet in the middle and re-epithelialise the gap completely.
 However, the proliferating epithelial cells do not cover the wound
completely until the granulation tissue from the base has started fill
the wound space.
 GRANULATION TISSUE: The main bulk of secondary healing is
by granulation. Granulation tissue is formed by proliferation of
fibroblasts and neovascularisation. The newly formed granulation
tissue is deep red, granular and very fragile. With time, it becomes
pale white due to increased in collagen and decreased blood supply.
 WOUND CONTRACTION: This phase is not seen in primary
healing. Due to the action of myofibroblasts present in granulation
tissue, the wound contracts to one-third of its original size. It occurs
during the formation of active granulation tissue.

83. DIFFERENCE BETWEEN 1˚ & 2˚ UNION OF WOUND
FEATURES PRIMARY SECONDARY
CLEANLINESS CLEAN NOT CLEAN
INFECTION NOT INFECTED INFECTED
MARGINS SURGICALLY CLEAN IRREGULAR
SUTURES USED NOT USED
HEALING SMALL GRANULATION
TISSUE
LARGE GRANULATION
TISSUE
OUT COME LINEAR SCAR IRREGULAR WOUND
COMPLICATION NOT FRQUENT FREQUENT

84. FACTORS AFFECTING WOUND HEALING
Local factors Systemic factors
INFECTION NUTRITIONAL FACTORS
LOCATION OF THE WOUND AGE OF THE PATIENT
IMMOBILISATION SYSTEMIC INFECTION
PHYSICAL FACTORS ADMINISTRATION OF
GLUCOCORTICOIDS
UNCONTROLLED DIABETES

85. FACTORS AFFECTING WOUND
HEALING
LOCAL FACTORS
 INFECTION:
It has been demonstrated that wounds which is completely
protected from bacterial irritation heal considerably more rapidly
than wounds which are exposed to bacteria or other mild
physical irritation.
 LOCATION OF THE WOUND:
wounds in the area in which there is a good vascular bed heal
considerably more rapidly than the area in which is relatively
avascular.

86.  IMMOBILISATION:
If the wound is in an area which is subjected to constant
movement so that formation of new connective tissue is
continuously distrupted (e.g.: corner of the mouth), it will result
in delayed wound healing.
 PHYSICAL FACTORS:
severe trauma to tissues is obviously a determinant in rapid
wound healing.
local temperature in the area of wound influences the rate of
healing. Thus, in environment hyperthermia, wound healing is
accelerated while in hypothermia it is delayed.
circulatory factors: anemia has been reported to delay wound
healing. Similarly dehydration also delays wound healing.

87. SYSTEMIC FACTORS
 NUTRITIONAL FACTORS:
Delay in the healing of wounds may occur in a person who is
deficient in variety of essential foods such as proteins, vitamins,
especially vitamin A, D and B complex.
 AGE OF THE PATIENT:
Wounds in younger persons heals more rapidly than wounds In
elderly persons and the rate of wound healing appears to be in
inverse proportion to the age of the patient.

88.  SYSTEMIC INFECTION
Delays healing of the wound.
 ADMINISTRATION OF GLUCOCORTICOIDS
It has an anti-inflammatory effect thus it delays wound healing.
 UNCONTROLLED DIABETES
Diabetics are more prone to develop infections thus delayed
wound healing takes place.
 HAEMATOLOGIC ABNORMALITIES
There is delayed wound healing

89. HEALING OF EXTRACTION WOUND
IMMEDIATE REACTION FOLLOWING EXTRACTION
 After the extraction, the blood which fills the socket coagulates,
red blood cells being entrapped in the fibrin meshwork.
 The resultant fibrin meshwork containing entrapped red blood
cells seals off the torn blood vessels and reduces the size of the
extraction of wound.
 Within the first 24-48 hours after extraction there are alterations
in the vascular bed.
There is vasodilation and engorgement of blood vessels in the
remnants of the periodontal ligament and the mobilization of
leucocytes to the immediate area around the wound.

90. FIRST WEEK WOUND
 Within the first week after tooth extraction, proliferation of
fibroblasts from connective tissue cells in the remnants of the
periodontal ligament is evident, and these fibroblasts have
begun to grow into the clot around the entire periphery.
 This clot forms the scaffold on which the cells associated with
healing process may migrate. It is the temporary structure.
 The epithelium at the periphery of the wound grow over the
surface of the organizing clot.

91.  Osteoclasts accumulate along the alveolar bone crest setting the
stage for active crestal resorption.
 Angiogenesis proceeds in the remnants of the periodontal
ligaments.

92. SECOND WEEK WOUND
 During the second week, the blood clot continues to get
organized through fibroplasia and new blood vessels that
penetrate towards the center of the clot.
 Trabeculae of the osteoid slowly extend into the clot from the
alveolus, and osteoclastic resoption of the cortical margin of the
alveolar socket is more distinct.
 The remnants of the periodontal ligament gradually undergo
degeneration and are no longer recognizable.

93. THIRD WEEK WOUND
 As healing continues into the third week , the original clot
appear completely organized by mature granulation tissue and
poorly calcified bone at the wound perimeter.
 The surface of the wound is re-epithelised with minimum or no
scar formation.
 Very young trabeculae of osteoid bone forms around the entire
periphery of the wound from the socket wall.

94.  The original cortical bone of the alveolar socket undergoes
remodeling so that it is no longer consist of such a dense layer.
 The crest of the alveolar bone is rounded off by osteoclastic
resoption.

95. FOURTH WEEK WOUND
 During the fourth week the wound begins the final stage of
healing, in which there is continued deposition and remodeling
resorption of the bone filling the alveolar socket.
 Much of this early bone is poorly calcified, as is evident from
its general radiolucency on the radiograph.
 Radiographic evidence of bone formation does not become
prominent until the sixth or eighth week after tooth extraction.

96. HEALING AFTER EXTRACTION OF
TOOTH
1- immediate reaction after extraction
2-second week after extraction
3-third week after extraction
4-six to eight weeks after extraction (complete
healing)

98. COMPLICATION OF HEALING OF
EXTRACTON WOUND
 DRY SOCKET
 FIBROUS UNION
DRY SOCKET
 The most common and painful complication in the healing
of human extraction wound is alveolar osteitis or dry
socket.
 It is basically a focal, in which the blood clot has
disintegrated or been lost.
 The condition is extremely painful without suppuration and
the presence of foul odor.

99.  The condition derives its name from the fact that after the
clot is lost the socket has a dry appearance because of the
exposed bone.
 It is more commonly associated with difficult and traumatic
extractions like the removal of impacted third molars.
 Destruction of the clot is caused by the proteolytic enzymes
produced by bacteria or local fibrinolytic activity.

100. DRY SOCKET

101. FIBROUS HEALING OF EXTRACTION WOUND
 It occurs more frequently when the extraction is accompanied
by the loss of both the buccal and the lingual cortical plates of
bone and the loss of periosteum as well.
 On a radiograph the lesion appears as a well circumscribed
radiolucent area in the site of a previous extraction wound .
 There is no certain way of differentiating fibrous healing from
the residual infection like residual cyst or granuloma.
 The areas of fibrous healing consists of dense bundles of
collagen fibrils with occasional fibrocytes and few blood
vessels. The lesion is a fibrous scar tissue with little or no
evidence of ossification.

102. HEALING OF FRACTURE
IMMEDIATE EFFECTS OF FRACTURE
 When fracture of a bone occurs, the haversian vessels of the
bone are torn at the fracture site along with the vessels of the
periosteum and the marrow cavity. This evokes acute
inflammation in the soft tissue adjacent to the fracture line.
 Because of the disruption of the vessels, there is considerable
amount of blood in this general area and at the same time there
is loss of circulation and blood supply.

103.  Three major phase occurs:
1) Reactive phase:
-fracture and inflammation
-granulation tissue formation
2) Reparative phase:
-callus formation
-lamellar bone deposition
3) Remodelling phase:

104. REACTIVE PHASE
 Soon after fracture the blood vessels constrict, stopping any
further bleeding.
 Within a few hours after fracture, the extravascular blood cells
forms a blood clot called as Hematoma.
 All of the cells within the blood clot degenerate and die.
 Some of the cells adjacent to the fracture site also die, but
fibroblast survive and replicate forming a loose aggregates of
cells interspersed with small blood vessels known as
Granulation tissue.

105. REPARATIVE PHASE
 Days after fracture, the cells of the periosteum replicates.
 The Periosteal cells proximal (close) to the fracture gap
develops into chondroblasts which forms hyaline cartilage.
 Periosteal cells distal (far away ) from the fracture gap develops
into osteoblasts which forms woven bone.
 The fibroblast with in the granulation tissue develops in to
chondroblasts which also forms hyaline cartilage.

106.  The two new tissue grow in size until they meet their counter part
from other part of fracture.
This process is called as Callus formation.
Callus in Latin means overgrowth of hard skin.
 Composed of varied amounts of fibrous tissue, cartilage and
bone.
 The external callus consists of the new tissue which forms
around the outside of two fragments of bone.
 The internal callus is the new tissue arising from the marrow
cavity.

107. The next step is deposition of lamellar bone by replacing hyaline
cartilage and woven bone.
 The replacement process is called endochondral ossification.
 The lamellar bone begins forming soon after the collagen
matrix of either tissue becomes mineralized.
 The new bone is formed in the form of trabecular bone.

108. REMODELLING PHASE
 In this, the trabecular bone is replaced by compact bone.
 It takes 3-5 yrs depending on factors like type of fracture,
age of patient, or general condition of patients.

109. STAGES IN HEALING OF FRACTURE

110. COMPLICATIONS OF FRACTURE
HEALING
 DELAYED UNION OR NON UNION
This results when the calluses of the osteogenic tissue over
each of the two fragments fail to meet and fuse or when
endosteal formation of bone is inadequate.
 FIBROUS UNION
The Fractured ends of fragments are united by fibrous tissue,
but there is failure of ossification.
 LACK OF CALCIFICATION
This may occur in unusual circumstances of dietary deficiency
or mineral imbalance which is seldom seen clinically.

111. HEALING AFTER REPLANTATION
 Following replantation the clot forms between the root
surface and ruptured periodontal ligament.
 Proliferation of the fibroblasts and the endothelial cells
occurs in the periodontal ligament remnants on the side
of the alveolar bone.
 The reconnection of the periodontal ligament is evident
by the extension of collagen fibers from the cementum to
the alveolar bone.

112.  The epithelium is reattached to the tooth at the end of the
first week.
 Complete regeneration of the periodontal ligament takes
place between two to four weeks.
 In the course of time, a number of teeth results in
resorption or ankylosis.

113. COMPLICATIONS OF WOUND HEALING
 INFECTION
Wounds may provide a portal of entry to microorganisms.
Infections of the wound delay the healing process. Systemic
conditions such as diabetes mellitus, immunosuppressive state
etc. make the individual prone to infection.
 KELOID AND HYPERTROPIC SCAR
Keloids are overgrown scar tissues with no tendency for
resolution. They occur in wound, which heal without any
complications.

114. Hypertrophic scar occur in wounds where healing is delayed.
These scars are more cellular and vascular.
Keloid and hypertropic scars are not seen in the wounds of
the oral cavity.
PIGMENTARY CHANGES
These are common in healing of wounds on skin and may
appear and may appear as hyperpigmented and hypopigmeted
areas.
In oral cavity hypopigmented scars are less common but some
lesions leave hyperigmentation while healing e.g. lichenplanus,
lichenoid reactions.

115.  CICATRIZATION
Cicatrization refers to late reduction in the size of the scar
in contrast to immediate wound contraction. It a
complication due to burns on the skin.
 IMPLANTATION CYSTS
Epithelial cysts may slide and get entrapped in the wound
and later may proliferate to form implantation cysts.

116. Healing – NEW CONCEPTS
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.

117. 1) Robbin’s & Cotron Pathological basis of diseases
2) Essential pathology for dental students - Harsh mohan
3) Text book of oral pathology - Shafers
References……..

118. THANK YOU