The document provides an extensive overview of inflammation and wound healing, defining inflammation as a protective response to tissue injury and outlining its causes, types, and cellular events. It details the mechanisms of acute inflammation, including chemical mediators, and describes the processes of healing through repair and regeneration, emphasizing the differences between healing by first and second intention. Additionally, it discusses factors influencing wound healing and the phases involved in the healing process from initial injury through recovery.

1. INFLAMMATION
AND WOUND HEALING
KARISHMA
II MDS

2. CONTENTS
 Introduction
 Definition of inflammation
 Causes and types of inflammation
 Events in acute inflammation
 Chemical mediators of acute inflammation
 Healing of tissue by repair and regeneration
 Wound healing and its types
 Healing in specialized tissues
 Conclusion
 References

3. INTRODUCTION
INFLAMMATION (derived from LATIN word inflammare, (To set on
fire)is a localized protective response elicited by injury or destruction
of tissues which serves to destroy ,dilute the wall of both the injurious
agent and injured tissues

4. DEFINITION
 Inflammation is defined as the local response of living mammalian
tissues to injury due to any agent .It is a body defence reaction in order
to eliminate or limit the spread of injurious agent as well as to remove
the consequent necrosed cells and tissues
 John hunter (1973) stated “inflammation is not a disease
but a specific response that has a salutary effect on its host“

5. CAUSES OF INFLAMMATION
1.INFECTIVE AGENTS like bacteria ,viruses,and their toxins,fungi,parasites.
2.IMMUNOLOGICAL AGENTS like cell mediated and antigen antibody reactions.
3.PHYSICAL AGENTS like heat,cold,radiation,mechanical trauma
4.CHEMICAL AGENTS like organic and inorganic poisons
5.INERT MATERIALS such as foreign bodies

6. CARDINAL SIGNS OF INFLAMMATION
The roman writer CELSUS in 1st century
A.D named the famous 4 cardinal signs of
inflammation as:
 Rubor(redness)
 Tumor(swelling)
 Calor(heat)
 Dolar(pain)
 Functio laesa (loss of function)

7. TYPES OF INFLAMMATION
 Rapid onset
 Slow duration
 Accumulation of fluids and plasma
at the affected site
 Polymorphonuclear neutrophils as
inflammatory cells
 Represents early body reactions
followed by repair
 Slower onset
 Longer duration
 Occurs after the causative
inflammation persist for a longer time
 Lymphocytes ,plasma
cells,macrophages are chronic
inflammatory cells
 Simultaneous inflammation and repair
ACUTE
CHRONIC

8. ACUTE INFLAMMATION
Acute
inflammation
Vascular events
Haemodynamic
changes
Changes in
vascular
permeability
Cellular events
Exudation of
leucocytes
phagocytosis

9. HAEMODYNAMIC CHANGES
Transient
vasoconstriction
Persistant progressive
vasodilatation
Local hydrostatic
pressure
Slowing and stasis
Leucocyte migration

10. LEWIS EXPERIMENT
 Red line (vasodilation of micro
vasculature)
 Flare (bright reddish appearance
surrounding the red line due to
vasodilation of adjacent
arterioles)
 wheal(swelling or oedema due
to transudation of fluid)

11. CHANGES IN VASCULAR PERMEABILITY
The appearance of Inflammatory oedema due to increased
vascular permeability of microvasculature bed is explained on
the basis of “STARLINGS HYPOTHESIS”
In normal circumstances ,the fluid balance is maintained by two
sets of forces
1)Forces that causes outward movement of fluid from
microcirculation are INTRAVASCULAR HYDROSTATIC PRESSURE and
OSMOTIC PRESSURE OF INTERSTITIAL FLUID
2)Forces that causes inward movement of fluid into circulation
are INTRAVASCULAR OSMOTIC PRESSURE and HYDROSTATIC PRESSURE
OF INTERSTITIAL FLUID

12.  Left over fluid in the interstitial compartment is drained away by
lymphatics and thus no oedema results normally in inflamed tissue
 Endothelial lining of microvasculature becomes more leaky
 Consequently ,intravascular osmotic pressure decreases and
osmotic pressure of interstitial fluid increases resulting in
excessive out flow of fluid into the interstitial compartment which
is exudative inflammatory oedema

13. MECHANISM OF INCREASED VASCULAR PERMEABILITY
1) ENDOTHELIAL CELL CONTRACTION
• Microvasculature;
• Venules response type; immediate (15 - 30min)
pathogenesis;
• By mediators like histamins,bradikinins,others
example; mild thermal injury

14. DIRECT ENDOTHELIAL CELL INJURY
• Cell necrosis and detachment;
• All microvasculature;
• Increase in permeability might be immediately after injury and last for severa
hours or days.
example; moderate to severe burns,bacterial infection,etc
ENDOTHELIAL CELL RETRACTION
• Microvasculature;
• Venules response type ;delayed prolonged path;
Cytokines - IL-1.TNF ;
• 4-6 hours

15. LEAKINESS IN NEOVASCULARISATION
Newly formed capillaries
Vascular endothelial growth factor
During repair and in tumuors
LEUCOCYTE MEDIATED ENDOTHELIAL INJURY
Microvasculature ;venules response type ;
activated leucocytes(proteolytic enzymes and toxic 02 species)
delayed prolonged pathogenesis;
Example; pulmanary venules and capilaries

16. CELLULAR EVENTS:
- Exudation of leucocytes
- Phagocytosis

17. EXUDATION OF LEUCOCYTES
1)MARGINATION AND PAVEMENTING
2)ADHESION OR ROLLING
- Selectins
- Integrins
- Immunoglobulin gene super family
adhesion molecules

18. 3)EMIGRATION – Diapedesis
4)CHEMOTAXIS – leukotrienes
- Cytokines
- Components of complement
system
- Soluble bacterial products

19. PHAGOCYTOSIS
Phagocytosis is defined as the process of engulfment of solid particulate
material by the cells(cell eating) The cells performing this function are called
phagocytes.
There are two types of phagocytic cells
- PMNs
- Macrophages
Neutrophils and macrophages in the tissue space produce several proteolytic
enzymes such as lysosymes, proteases, collagenase, elastase, lipase,
proteinase,gelatinase and acid hydrolases.
These enzymes degrade collagen and extra cellular matrix.

20. STAGES IN PHAGOCYTOSIS
1) ATTACHMENT STAGE
• Opsonised microbes attaches to phagocytic surface receptors
• Opsonin are naturally occurring factors in the serum
• Two main opsonins present in the serum are IgG opsonin and
C3b opsonin and their corresponding receptors on the surface of
phagocytes

21. 2)ENGULFMENT STAGE
Cytoplasmic extensions surround and engulf the bound opsonised
microbe by formation of pseudopods around the particle ,enveloping it
in a phagocytic vacuole or phagosome.
• This phagosome fuses with the lysosome
of cell to form phagolysosome

22. 3)KILLING (OR) DEGRADATION STAGE
• In this stage the microbes embedded in phagosome is killed by
antimicrobial or bactericidal substances present in granules of
phagocytes and degraded by hydrolytic enzymes synthesised by
phagocytes.
• These antimicrobial agents acts by either of the
following mechanisms;
1) Intracellular (Oxidative,Non-oxidative)
2) Extracellular

23. CHEMICAL MEDIATORS OF INFLAMMATION

24. VASOACTIVE AMINES
A)HISTAMINE:
Histamine is stored in the granules of mast cells,basophils,and platelets
Histamine is released from these cells by various agents like:
a)Stimuli or substances inducing acute inflammation eg; heat ,cold,trauma,
irritant chemicals etc
b) Histamine releasing factors from neutrophils,monocytes,and platelets,
c) Anaphylotoxin like fragments of complement C3a.C5a.
d) Interleukins
The main action of histamine are vasodilation,increase vascular
permeability,itching and pain

25. B) 5-HYDROXYTRYPTAMINE(5-HT OR SERATONIN )
It is present in tissues like chromaffin cells of GIT,spleen,nervous tissues,mast
cells,and platelets
The action of Serotonin is similar to histamine but it is a less potent mediator
of increased permeability and vasodilation than histamine
C) NEUROPEPTIDES:
These are the small peptides produced in CNS and PNS (substance p, neurokinin
etc)
Actions:- 1) inc,vascular permeability
2) pain stimulus transmission
3) mast cell degranulation

26. ARACHIDONIC ACID METABOLITES
Arachidonic acid is a fatty acids and is a constituent of phospholipid cell
membrane besides obtaining through diet.(essential fatty acids – linoleic
acid – arachidonic acid)
 Arachidonic acid metabolites are most potent inflammatory mediators
than oxygen free radicals which are obtained via two main pathways
A) Cyclo-oxygenase pathway(prostaglandins, thromboxaneA2,protacyclin)
B) Lipo-oxygenase pathway(5-HPETE (5- hydroperoxy eico-satetraenoic
acid),Leukotriens)

28. *Hydroperoxy eicosatetraenoic acid

29. LYSOSOMAL COMPONENTS
The inflammatory cells contains lysosomal granules which on release
elaborate a variety of mediators of Inflammation,They are as follows
a)Granules of neutrophils
b)Granules of monocytes and tissue macrophages
a)GRANULES OF NEUTROPHILS
 primary granules (myeloperoxidase)
 secondary
granules(lactoferrin,lysozyme, alkaline
phosphatase,collagenase )
b)GRANULES OF MONOCYTES AND TISSUE
MACROPHAGES
 Releases mediators like acid
proteases,collagenase,elastase, and
plasminogen

30. PLATELET ACTIVATING FACTOR(PAF)
It is released from IgE sensitised basophils,or mast cells .Actions of
PAF as mediators of inflammation are
a)increased vascular permeability
b)vasodilation in low concentration and vasoconstriction in higher
concentration
c)Bronchoconstriction
d)adhesion of leukocytes to endothelium
e)chemotaxis

31. CYTOKINES
 Cytokines are lower molecular weight regulatory proteins or
glycoproteins(polypeptide substances) secreted by activated lymphocytes
(lymphokines) and Monocytes(monokines)
 Main cytokines acting as a mediators of inflammation are as follows
Interleukin-1(IL-1); Tumour necrosis factor( alpha.beta);
Interferon(gama) and chemokines(IL-8.PF-4)

32. OXYGEN METABOLITES
1) They are released from activated neutrophils and macrophages
2) Includes superoxide,H2O2,,,toxic NO products are few oxygen
metabolites
3) Role of oxygen metabolites as inflammatory mediators includes
- vascular permeability by endothelial cell damage,
- activation of protease,
- damage of other cells,

33. NITRIC OXIDE METABOLITES
 Nitric oxide was originally described as vascular relaxation factor
,it has recently been included as a mediators of inflammation
 Nitric oxide has been shown to have fungicidal and anti parasitic
action
 Role of Nitric oxide in the inflammation are vasodilation,
antiplatelet activating agent, microbicidal action, etc

34. PLASMA DERIVED MEDIATORS (plasma proteases)
These include various products derived from activation and interaction
of 4 inter linked systems as follows:
a)The Kinin system
b) The Clotting system
c)The fibrinolytic system
d)The complement system

35. Effects of bradykinin are:
- Smooth muscle Contraction,
- vasodilation(hypotension),
- Increases vascular Permeability(edema),
and - Involved in mechanism of pain.

36. Action of fibrinopeptides in
inflammation are:
a)Increased vascular
permeability b)chemotaxis for
leucocytes

38. ACTION OF ANAPHYLOTOXINS
IN INFLAMMATION
• Release of histamine from
mast cells and basophils
• Increased vascular
permeability
• C3a augments for leucocytes
• C5a is chemotactic for
leucocytes
• Action of MAC is to cause
pores in the cell membrane of
the invading microbes

39. SYSTEMIC EFFECTS OF ACUTE INFLAMMATION :
1)Leucocytosis
2)Lymphadenitis
3)Pyrexia
4)Shock (in severe cases)

40. FATE OF ACUTE INFLAMMATION
Fate of acute
inflammation
Resolution
Healing
Suppuration
Chronic
inflammation

41. Healing is the body’s response to injury in an attempt to restore normal
structure and function
HEALING
HEALING
REGENERATION
REPAIR

42. REGENERATION :
 When healing takes place by proliferation of parenchymal cells and
usually results in complete restoration of the original tissues
 The goal of all surgical procedure should be regeneration which returns
the tissues to their normal microstructure and function
 Depending upon their capacity to divide,the cells can be divided into
- labile cells
- stable cells
- permanent cells

43. REPAIR :
 It is a healing outcome in which tissues do not return to their normal
architecture and function
 Repair typically results in the formation of scar tissues
 Repair process takes palce by
- Granulation tissue formation
- Contraction of wounds

44. FORMATION OF GRANULATION TISSUE
1)PHASE OF
INFLAMMATION
(acute inflammatory
response within 24
hours)
2)PHASE OF CLEARANCE
proteolytic enzymes from
neutrophils, autolytic
enzymes from dead tissue
cells ,phagocytic activity of
macrophages clear off the
necrotic tissues, debris and
RBC
3)PHASE OF IN GROWTH OF
GRANULATION
 Angiogenesis
 Formation of fibrous
tissue

45. WOUND HEALING

46. WOUND:
A wound is a break in the integrity of the skin or tissue often which may
be associated with disruption of the structure and function
WOUND HEALING is a combination of repair and regeneration which
can be accomplished in two ways:
 Healing by first intention(primary union
 Healing by second intention(secondary union)

47.  Wound is clean and uninfected
 Without much loss of cells and
tissues
 Edges of wound are
approximated by surgical
sutures
 Wound is open with large
tissue defect,at times infected
 Having extensive loss of
tissues
 The wound is not
approximated by surgical
sutures but is left open
PRIMARY UNION SECONDARY UNION

48. HEALING BY FIRST INTENSION (PRIMARY UNION)
1) INITIAL HAEMORRHAGE
 Immediately after injury,the space between the approximated
surfaces of incised wound is filled with blood
 The filled blood clots seals the wound against dehydration and
infection
2) ACUTE INFLAMMATORY RESPONSE
 This occurs within 24 hrs with appearance of PMN from the
margins of incised wound
 By 3rd day ,polymorphs are replaced by macrophages

49. 3)EPITHELIAL CHANGES
 The basal cells of epidermis from both the cut margins start
proliferating and migrating towards incisional space in the form of
epithelial spurs
 These migrated epithelial cells separate the under lying viable dermis
from the overlying necrotic material and clot forming a SCAB
 By 5th day ,a multilayered new epidermis is formed which is
differentiated into superficial and deep layers
 A well approximated wound is covered by a layer of epithelium in
48hours

50. ORGANISATION:
 By 3rd day ,fibroblast also invade the wound area.
 By 5th day ,new collagen fibrils start forming which dominate till healing
is completed
 By 4th week,the scar tissue with scanty cellular , vascular elements with
few inflammatory cells and epithelialised surface is formed

51. HEALING BY SECONDARY INTENTION(SECONDARY UNION)
1)INITIAL HAEMORRHAGE
As a result of injury ,the wound space is filled with blood and
fibrin clot which dries
2)INFLAMMATORY PHASE
There is an initial acute inflammatory response followed by
appearence of macrophages which clear of the debris as in primary
union

52. EPITHELIAL CHANGES
 As in the primary healing, the epidermal cells from both the margins
of the wound proliferate and migrate into the form of epithelial spurs
till they meet in the middle and reepithelialise the gap completely
 These proliferated epithelial cells do not cover the surface fully until
granulation tissue from the base has started filling the wound space
 After these epithelial cells meet in the middle they separate the
underlying viable tissues from necrotic tissue at the surface forming
scab

53. GRANULATION TISSUE FORMATION
 The main bulk of secondary healing is by granulation
 Granulation tissue is formed by proliferation of fibroblasts and
neovascularisation from the adjoining viable elements
 The newly formed granulation tissue is deep red,granular and very
fragile
 The specialised structure of skin like hair follicle and sweat glands are
not replaced unless their viable residues remain which may regenerate

54. WOUND CONTRACTION
 Contraction of wound is an important feature of secondary healing
,and not seen in primary healing
 Wound contraction occurs at a time when active granulation tissues
is being formed(approximately 4 to 5 days after wounding )
 Due to the action of myofibroblasts present in granulation tissue,the
wound contracts to one third of its original size
 Maximal contraction occurs for 12 to 15 days although it will
continue if wound remain opens

56. COMPLICATION OF WOUND HEALING
1)Infection
2)Pigmentation
3)Deficient scar formation
4)Incisional hernia
5) Hypertrophied scar and keloid formation
6)Excessive contraction of wound
7)Epidermal cyst formation

57. EXTRACELLULAR MATRIX (WOUND STRENGTH )
1) The wound is strengthened by
proliferation of fibroblast and
myofibroblast which gets structural
support from the extracellular
matrix (ECM)
2) In addition to providing structural
support ,ECM can direct cell
migration,attachment,
differentiation,and organisation

58. The main components of Extracellular matrix are:
- Collagen
- Basement membrane
- Proteoglycans
- Elastic fibers
- Adhesive glycoproteins

59. FACTORS INFLUENCING WOUND HEALING
 Infection
Delays wound healing
 Poor blood supply
slows healing process
 Foreign bodies
causes intense inflammatory reaction and infection
 Exposure of ionising radiation
Delays granulation tissue formation
 Type,size&,location of injury
Determines whether healing takes place by resolution or organisation
LOCAL FACTORS

60. SYSTEMIC FACTORS
 Age
wound healing is rapid in young age,and somewhat slow in aged
people
 Nutrition
Deficiency of constituents like protein,vitamin C ,zinc delays
wound healing
 Systemic diseases
Uncontrolled diabetis , Immuno suppressive diseases like HIV,
Auto immune diseases like SLE,Haematologic diseases like
anemia,neutropenia,bleeding disorders slows healing process
 Other factors
smoking,obesity,alcohol,stress,etc

61. HEALING OF EXTRACTION WOUNDS:
Immediate reaction following extraction:
1. Blood coagulation
2. Vasodilatation
3. Mobilization of Leucocytes
4. Collapse of unsupported gingival
tissue into position Clot contraction

62. First week wound:
Periphery
 Fibroblast proliferation
 Angiogenesis
 Proliferating epithelium
 Osteoclastic activity at
crest
Center
 Blood clot
 Layering of leucocytes
 Fibroblast infiltrate &
microvasculation
 Granulation tissue

63. Second week wound:
Periphery
 PDL degeneration
 Frayed socket wall
 Outwardly extended osteoid
trabeculae
 Epithelial proliferation
Center
 Organisation of blood clot

64. Third week wound
Complete epithelialization
Organised clot
Young trabeculae of osteoid bone at periphery
Crest of alveolar bone rounded off by resorption

65. Fourth week wound:
Continuous deposition remodelling and resorption of bone
filling alveolar socket
Radiological evidence of bone not prominent till sixth or
eight week after extraction
Radiological evidence of differences in new bone of
alveolar socket and adjacent bone is evident at four to six
months

66. COMPLICATIONS OF EXTRACTION WOUND HEALING:
Dry socket:
Dry socket (alveolar osteitis) is a painful dental condition
that sometimes happens after you have a permanent
adult tooth extracted.
Dry socket is when the blood clot at the site of
the tooth extraction fails to develop, or it dislodges or
dissolves before the wound has healed.

67. ROLE OF TOPICAL USE OF INSULIN IN HEALING OF CHRONIC ULCER
Gaurav Goenka, Virendra S. Athavale, Dakshayani S. Nirhale, Nitin Deshpande, Kunal Agrawal, Murtuza Calcuttawala
Department of General Surgery, Padmashree Dr. D. Y. Patil Medical College Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth,
Pimpri, Pune, Maharashtra, India
Objectives: To study the efficacy of topical use of insulin in wound healing in following terms:-(1) rate of wound
healing; (2) safety evaluation; (3) hospital stay.
Materials and Methods: This was a prospective study carried out in a tertiary health centre from July 2010 to
September 2012 in 50 patients after taking an informed and written consent of the patients having chronic ulcer.
All the patients were randomized into two groups, Group A and Group B. Each group was again sub-divided into
1 and 2 i.e. sub-group A1, A2 and sub-group B1, B2. Patients with diabetes were grouped as A1 and B1 and non-
diabetic patients were grouped as A2 and B2. Group A patients were treated with insulin dressings and Group B
patient’s ulcers were treated with normal saline dressings. Ulcer size and healing was recorded on weekly basis.
Strict glycemic control was maintained in all diabetic patients. Results were compared at complete healing or at
the end of 12 weeks which ever was earlier.
Results: Our study included both diabetic and non-diabetic patients. There was no significant change in BSL(R)
values after use of insulin on wounds. The number of days required for wound healing in Group A patients in both
subgroups (A1 and A2) was significantly less as compared to Group B (B1 and B2). The mean rate of healing of
wounds was much faster in Group A as compared to Group B. The hospital stay in Group A patients was
significantly less than Group B.
Conclusion: The use of topical Insulin strongly suggests accelerated wound healing in chronic ulcer. Topical
insulin in chronic ulcer is safe and effective without any systemic side effect. Topical insulin significantly reduces
the hospital stay of patients with chronic ulcers. Early return to work decreased economical load.

68. Healing in specialized tissue
Bone fracture is a medical condition in which there is a break in the
structural continuity of bone or periosteum
Bone fracture can be the result of high force impact or stress , trauma or due
to certain medical conditions that weakens the bone
Word fracture derived from latin word “fractura” means ‘to break

69. Healing of skin wound is a combination of repair and regeneration.
However, in certain specialized tissues, either repair or regeneration may
predominate.one of such example is fracture healing
FRACTURE HEALING
 Fracture healing depends upon the type of fracture:
FRACTURE HEALING MECHANISM
PRIMARY UNION
SECONDARY UNION
PROCALLUS FORMATION
OSSEOUS CALLUS FORMATION
REMODELLING

70. PRIMARY UNION OF FRACTURE
 Mechanism of bone healing seen when there is no motion at the fracture site
(ie; Rigid internal fixation )
 Bony union takes place with formation of medullary callus without periosteal callus
formation
 Slow healing process with extensive bone necrosis
PRIMARY FRACTURE UNION
CONTACT HEALING
Haversian remodelling directly across the
fracture site if no gap exists
GAP HEALING
Deposition of lamellar bone if small gaps exists

72. SECONDARY UNION
The secondary union is the more common process of f racture healing
and is described under 3 stages:
- Procallus formation
- Osseous callus formation
- Remodelling

73. STEPS INVOLVED IN PROCALLUS FORMATION:
a) Haematoma
b)Inflammatory resonse
c) Ingrowth of granulation tissue
d)Callus composed of woven bone and cartilage

74. OSSEOUS CALLUS FORMATION
 The woven bone is cleared away by incoming osteoclasts and the
calcified cartilage disintegrate
 In their place ,newly formed blood vessels and osteoblasts invade
 These osteoblasts lay down calcified osteiods and as a result, lamellar
bone is formed by developing haversian system concentrically around
the blood vessels

75. BONE REMODELLING
 The remodelling process substitutes the lamellar bone(trabecular bone)
with compact bone
 The Trabecular bone is first resorbed by osteoclasts,creating a shallow
resorption pit known as “HOWSHIPS LACUNA”.
 Then osteoblast deposit compact bone within the resorption pit
 As when the compact bone is formed in place of intermediate callus
,Eventually the external callus is cleared away,and the bone marrow cavity
develops in internal callus

76. COMPLICATION OF FRACTURE HEALING
1)FIBROUS UNION
Occurs if the immobilisation of fractured bone is not done ,occasionally a
false joint may develop which is called as pseudo arthrosis
2) NON UNION
Results if some soft tissue interposed between the fractured ends
3)DELAYED UNION
Can occur as a result of infection,poor nutrition ,inadequate blood supply,old
age,etc

77. CONCLUSION

78. REFERENCES
 Pathology for Dental students –Harshmohan ,2nd edition
 Robbins Basic pathology –9th edition
 SHAFERs Textbook of Oral pathology – 7th edition
 Internet Sources