Inflammation and wound healing is a complex process involving several steps. It begins with an acute inflammatory response triggered by injury or infection, characterized by redness, swelling, heat and pain. This response involves increased vascular permeability, migration of white blood cells, and release of chemical mediators. Over time, the inflammatory response transitions to a chronic phase involving lymphocytes and macrophages. Wound healing occurs through regeneration or repair, involving re-epithelialization, granulation tissue formation, collagen deposition and wound contraction. Primary healing closes wounds through direct apposition of wound edges, while secondary healing relies on granulation tissue to fill open wounds.

1. INFLAMMATION
AND WOUND HEALING

2. CONTENTS
Basic mechanism involved in the process of inflammation and repair:
Introduction
Clinical signs of inflammation
Different types of Inflammation
Mechanism of Inflammation – Alteration in vascular permeability and blood
flow, migration of WBC’s
Mediators of inflammation
Basic principles of wound healing in the skin

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
 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
 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
CHRONIC

8. ACUTE INFLAMMATION
Acute
inflammation
Haemodynamic
changes
Vascular events
Changes in
vascular
permeability
Exudation of
leucocytes
Cellular events
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. ENDOTHELIAL CELL RETRACTION
• Microvasculature;
• Venules response type ;delayed prolonged path;
Cytokines - IL-1.TNF ;
• 4-6 hours
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

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

16. CELLULAR EVENTS:
- Exudation of leucocytes
- Phagocytosis

17. EXUDATION OF LEUCOCYTES
1) MARGINATION AND PAVEMENTING
MARGINATION : Cells line up against the endothelium.
PAVEMENTING : Sticking of white blood cells to the
linings of the finest blood vessels (capillaries) when
inflammation occurs. WBC’s gather along the
endothelium, like bricks paving a road). From here the
leukocytes crawl between the endothelial cells and
enter the inflamed connective tissue.
2)ADHESION OR ROLLING :
Adhesion – connecting to the endothelial wall.
ROLLING: neutrophils roll over endothelial cells
- Selectins
- Integrins
- Immunoglobulin gene super family adhesion
molecules

18. 3)EMIGRATION – Diapedesis
Neutrophils undergo lateral migration or
crawling on endothelial cells to find a permissive
site for transmigration. Movement of leukocytes
out of the circulatory system and towards the
site of tissue damage or infection.
 CHEMOTAXIS –
Chemotaxis is a fundamental
biological process in which a
cell migrates following the
direction of a spatial cue. This
spatial cue is provided in a
form of a gradient of
chemoattractants.
Chemotaxis of
leukocytes, a requisite process
for neutrophil extravasation from
the blood into tissues, is a critical
step for initiating and maintaining
inflammation in both acute and
chronic inflammation.

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.

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) 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) Increase vascular permeability
2) pain
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

27. 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

28. 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 toendothelium
e)chemotaxis

29. 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)

30. 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,

31. 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

32. 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

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

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

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

37. 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

38. 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 place by
- Granulation tissue formation
- Contraction of wounds

39. WOUND HEALING

40. 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)

41.  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

42. 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 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

43. 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

44. 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

45. 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

46. 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

47. 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

48. 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 to15 days although it will
continue if wound remain opens

50. 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

51. REFERENCE : TEXT BOOK OF PATHOPHYSIOLOGY BY DR.
MADAN KAUSHIK; Page no:42-76
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