You are on page 1of 46

INFLAMMATION AND WOUND HEALING

CONTENTS

 INTRODUCTION

 DEFINITION

 CAUSES OF INFLAMMATION

 SIGNS OF INFLAMMATION

 TYPES OF INFLAMMATION

 ACUTE INFLAMMATION

o VASCULAR EVENTS

o CELLULAR EVENTS

 CHEMICAL MEDIATORS OF INFLAMMATION

o CELL DERIVED MEDIATORS

o PLASMA DERIVED MEDIATORS

 INFLAMMATORY CELLS

 MORPHOLOGY AND SYSTEMIC EFFECTS OF ACUTE INFLAMMATION

 CHRONIC INFLAMMATION

o GENERAL FEATURES OF CHRONIC INFLAMMATION

o TYPES OF CHRONIC INFLAMMATION

 WOUND HEALING

o HEALING BY PRIMARY INTENTION

1
o HEALING BY SECONDARY INTENTION

o FACTORS EFFECTING WOUND HEALING

o HEALING OF AN EXTRACTED SOCKET

 REFERENCES

2
INTRODUCTION

The term inflammation is derived from Latin word inflammare meaning to burn.

It is a series of pathological changes associated with localized vascular

reaction and cellular response of the living tissue to an injury insufficient to kill the tissue. The

effect of inflammation is twofold i.e.to destroy or remove the causative agent and to repair the

damaged tissue. For the first action wandering mesodermal cells of blood or tissue come to

action, but for the second one, fixed cells of the tissue take part. Inflammation may cause

considerable harem to the body as well. Ex- Anaphylaxis to bites, drugs, toxins, atherosclerosis,

chronic rheumatoid arthritis, fibrous bands, adhesion to intestinal obstruction.

DEFINITION

Inflammation is defined as the local response of living mammalian tissues to injury due to any

agent. It is a body defense reaction in order to eliminate or limit the spread of injurious agent as

well as to remove the consequent necrosed cells and tissues.

Harsh Mohan. Text book of pathology.6th Edition, page no-133.

3
ETIOLOGY

A.NON LIVING

1. Mechanical agents-Injury to trauma, presence of foreign body, ligature, dead tissue,

sequestrum.

2 .Physical agents-Thermal (heat or cold), electric burn,x-ray, radium.

3.Chemical agents- Chemical and organic poisons,strong acid and alkali.

4. Immunological agents- Antigen antibody reactions, cell mediated immunological reactions,

and auto immune diseases.

5. Metabolic disorders- These include disturbances in iron, copper, bile pigments and purine

metabolism.

6. Nutritional imbalances-These include deficiencies or excess in specific vitamins.

7. Certain stimuli such as toxins,bacteria and ischemia cause cell necrosis directly and the

necrotic tissue in turn can trigger the release of inflammatory mediators.

B.LIVING- Bacteria, fungi, viruses, parasites.

4
SIGNS OF INFLAMMATION

The essential cardinal signs of inflammation were formulated by Celsus (30BC-38AD) using the

Latin words rubor, calor, tumor, dolar.

To these, fifth sign funticolaesa (loss of function) is added by Virchow.

RUBOR (RED NESS)- An acutely inflamed tissue appear red. Ex-Skin affected by sun burn,

cellulites due to bacterial infection or acute conjunctivitis. This is due to dilation of small blood

vessels within the damaged area.

CALOR (HEAT) - Increase in temperature is seen only in peripheral parts of the body, such as

skin. It is due to increased blood flow (hyperemia) through the region resulting in vascular

dilation and the delivery of warm blood to the area.

TUMOR(SWELLING)-Swelling results from odema-the accumulation of fluid in to the extra

vascular space as part of the fluid exudates and to a much lesser extent from the physical mass of

the inflammatory cells migrating in to the area. As the inflammation response progress,

formation of new connective contributes to the swelling.

DOLAR (PAIN) - For the patient,pain is one of the best known features of acute inflammation. It

results partly from the stretching and distortion of tissues due to inflammatory odema and in

particular, form pus under pressure in an abscess cavity. Some of the chemical mediators of

acute inflammation including bradykinin, prostaglandins and serotonin are known to induce pain.

FUNCTIO LAESA(LOSS OF FUNCTION)- MOVEMENT OF AN INFLAMMED AREA IS

consciously and reflexly inhibited by pain,while severe swelling may physically immobilize the

tissue.

5
TYPES OF INFLAMMATION

Depending upon the defense capacity of the host and duration of response, inflammation can be

classified as acute and chronic inflammation.

1. ACUTE INFLAMMATION-It is of short duration, represents the early body reaction and is

usually followed by repair. The main features of acute inflammation are

a) Accumulation of plasma and fluid at the accumulated site.

b) Intra vascular activation of platelets.

c) Polymorphonuclear neutrophils as the inflammatory cells.

2. CHRONIC INFLAMMATION – is of longer duration and occurs of the causative agent of

acute inflammation persists for longer time, or the stimulus is such that it induces chronic

inflammation from the beginning. The general characteristic feature of chronic inflammation is

presence of chronic inflammatory cells such as lymphocytes, plasma cells and macrophages.

Chronic inflammation is sub divided in to chronic nonspecific

inflammation and chronic granulomatous inflammation.

6
ACUTE INFLAMMATION- The major physiological events, which occur during an acute

inflammatory response are,

A) Vascular changes

B) Cellular events

A) Vascular events: Alteration in the micro vasculature is the earliest response to tissue

injury. These alterations include hemodynamic changes and changes in vascular

permeability

 Heamodynamic changes- The earliest feature of inflammatory response results

from changes in the vascular flow of small blood vessels in the injured tissues.

These changes are,

a) Transient vasoconstriction is the immediate vascular response. In mild form of

injury,the blood flow is re-established in 3-5 seconds while with severe injury the

vasoconstriction may last for about 5 minutes.

b) Persistent progressive vasodilation follows,which involves mainly the arterioles.

The change is obvious within half an hour of injury. Vasodilation results in increased

blood volume in micro vascular bed of the area,thus redness and warmth are felt at

the site of acute inflammation.

c) Local hydrostatic pressure is elevated as a result of progressive vasodilation and

transudation of fluid occurs in to extra vascular space. This leads to swelling at the

local site of inflammation.

7
d) Slowing or stasis follows, which is attributed to increased permeability of

microvasculature that results in increased concentration of red cells and thus raised

blood viscosity.

e) Leukocyte migration or peripheral orientation of leukocytes along the vascular

endothelium occurs. The leukocytes stick to the vascular endothelium briefly and then

move and migrate through the gaps between endothelial cells in to the extra vascular

space. This process is known as emigration.

MARGINATION AND PAVEMENTING

8
The features of heamodynamic changes in inflammation are best demonstrated by Lewis

experiment known as triple response or red line response consisting of red line, flare and

wheal.

I. Red line appears within a few seconds following stroking and results from

vasodilation of capillaries and venules.

II. Flare is flush surrounding the red line,results from vasodilation of adjacent

arterioles

III. Wheal is swelling or oedema of the surrounding skin due to transudation of fluid

in to extra cellular space

 Altered vascular permeability

In the inflamed tissue there is accumulation of oedema fluid in the interstitial component

which come from blood plasma by its escape through the endothelial wall of peripheral

vascular bed. In initial stages the escape of fluid is due to vasodilation and elevation of

hydrostatic pressure. This fluid is transudate in nature, later increased vascular

permeability of micro circulation leads to formation of exudate.

The appearance of inflammatory oedema due to increased vascular

permeability of micro vascular bed is explained on the basis of starling’s hypothesis

In normal condition, the fluid balance is maintained by two opposing sets of forms

1) Forces that cause outward from microcirculation are intravascular hydrostatic pressure and

osmotic pressure of interstitial fluid.

9
2) Forces that cause inward movement are intrasulcular osmotic pressure and hydrostatic

pressure of interstitial fluid.

The little left in the interstitial component is drained away by lymphatics and thus no oedema

results.

However in inflammatory cells, the endothelial lining of microvasculature become more leaky,

consequently intravascular osmotic pressure decreases and osmotic pressure of interstitial fluid

increases resulting in excessive outward flow of fluid into the interstitial compartment which is a

An exudative inflammatory oedema.

INVREASED VASCULAR LEAKAGE IN ACUTE INFLAMMATION

10
Mechanism of increased vascular permeability

The endothelial lining of microvasculature become leaky due to:

1. Contraction of endothelial cells- most common mechanism of increased leakiness and

affects venules exclusively, while capillaries and arterioles remain unaffected. The

endothelial cells develop temporary gaps between them due to their contraction. It is

mediated by the release of histamine, bradykinin and other chemical mediators. The

response begin immediately after injury, is usually reversible and is for short duration (

15-30 minutes)

2 Retraction of endothelial cells: Structural re-organization of the cytoskeleton of endothelial

4cells occurs that causes reversible reaction at intracellular cells occurs that cause’s

reversible reaction at intercellular junctions. This also effects venules and is mediated by

cytokines such as interleukin -1 (Il-1) and tumor necrosis factor (TNF). The onset of

responses takes 4-6 hours after injury and lasts for 2-4 hours or more.

3) Direct injury to endothelial cells: direct injury to the endothelium causes cell necrosis and

appearance of physical gaps at the sites of detached endothelial cells. Process of thrombosis

is initiated at the site of damaged endothelial cells. The charge affects all levels of

microvasculature (venules, capillaries and arterioles). The increased permeability may either

appear immediately after injury or lasts for several hours or days.

4) Endothelial injury mediated by leukocytes: Adherence of leukocytes to the endothelium

at the site of inflammation may result in activation of leukocytes. These activated

11
leukocytes release proteolytic enzymes & toxic oxygen species which may cause

endothelial injury and increased vascular leakiness. Venules are mostly affected.

CONTRACTION OF ENDO THELIAL CELLS. RETRACTION OF ENDOTHELIAL CELLS

DIRECT INJURY TO ENDOTHELIAL CELL LEUCOCYTE MEDIATED ENDOTHELIAL INJURY

MECHANISM OF INCREASED VASCULAR PERMEABILITY

12
B) Cellular events:

The cellular phase of inflammation consists of

1. Exudation of leukocytes.

2. Phagocytosis.

Exudation of Leukocytes:

The sequence of events in the extravasation of leukocytes from the vascular lumen to the

extravascular space is divide into:

1. Margination and rolling

2. Adhesion and transmigration between endothelial cells.

3. Chemotaxis and activation

A) Margination& Rolling:

The normal axial flow consists of central stream of red and white blood cells and peripheral cell-

free layer of plasma close to vessel wall. As vascular permeability increases in early

inflammation fluid exerts vascular lumen and blood flows slowly. As a result leukocytes move

out of the central column, marginating to the vessels periphery. Subsequently, the leukocytes

tumble on the endothelial surface, transiently sticking along the way, a process called rolling.

B) Adhesion and Transmigration

Rolling is followed by formation of transient bond between the leukocytes and endothelial cells

becoming firmer. This is known as adhesion.

Rolling and adhesion are carried out by following adhesion molecules:

13
1. Selectins- mediate rolling of PMNs over endothelial surface.

2. Integrins on the endothelial surface are activated during the process of loose and transient

adhesions between endothelial cells and leukocytes. At the same time, the receptors for integrins

on the neutrophils are also stimulated. This process brings about firm adhesion between

leukocyte and endothelium.

3. Immunoglobulins superfamily adhesion molecule (ICAM-1,2) help in localizing leukocytes to

the site of tissue injury and this help in transmigration of PMN

After adhesion, the neutrophils move along the endothelial cells till a suitable site

between the cells is found where the neutrophil throw out cytoplasmic pseudopods. These

neutrophils lodged between the endothelial cells and basement membrane cross the basement

membrane by damaging it locally with secreted collagenase and escape out in to extravascular

space. This is known as transmigration or emigration.

Neutrophil are the dominant cells on acute inflammatory exudate in the first 24 hours and

monocyte macrophage appear in the next 24-48 hours

Simultaneous to emigration of leukocytes, escape of red cells through gaps between endothelial

cells takes place. This is known as diapedesis. It is a passive phenomenon. Diapedesis give

14
haemorrahgic appearance to the inflammatory exudates.

TRANSMIGRATION OF LEUCOCYTES

C) Chemotaxis and activation-

After extravasation leukocytes emigrate toward the site of injury along a chemical

gradient. In a process called transmigration. The exogenous and endogenous agents acting as

potent chemotactic substances.

For different leukocytes called chemokines are-

1. Leukotriene B4(LT-B4)

2. Platelet factor 4 (PF$)

3. Components of complement system (C3, C5 in particular)

4. Cytokines (Interleukins IL-1,Il-5, Il-6)

5. Soluble bacterial products (such as formylated peptides)

15
6. Monocyte chemoattractant protein (MCP-1)

7. Chemotactic factor for eosinophils.

These chemotactic agents bind to specific receptors on the leukocyte cell surface and induce an

intracellular cascade of phospholipid metabolites, eventually eliminating in increased

intracellular calcium. The increased cystolic calcium triggers the assembly off cytoskeletal

contractile elements necessary for movement.

The leukocytes move by extending pseudopods that anchor themselves to the extracellular matrix

and then pull the reminder of the cell after. Thus locomotion is stimulated in a specified

direction.

Besides stimulating locomotion, chemotactic factors also induce other leukocyte responses,

referred to as leukocyte activation

CHEMOTAXSIS BY FORMATION OF PSEUDOPODS

16
Phagocytosis:

Phagocytosis is defined as the process of engulfment of solid particulate material by the cells

(cell eating). These cells are known as phagocytes. There are 2 main types of phagocytic cells.

1. Polymorphonuclear neutrophils(PMNs) also called macrophages.

2. Circulating monocytes and fixed tissue mononuclear phagocytes called as macrophages.

Phagocytosis involves following 4 steps:

a) Recognition & attachment stage

b) Engulfment stage.

c) Secretion (degranulation)stage

d) Digestion or degradation stage.

a) Recognition & attachment stage

17
STAGES OF PHAGOCYTOSIS

Chemotactic factors released by bacterial products as well as by tissue proteins attract

phagocytic cells. In order to form a bond between bacteria and the cell membrane of phagocytic

cell, the micro-organisms get coated with opsonin which are naturally occurring factors in serum

and the receptors of these opsonin are present in phagocytic cells. The main opsonin are:

1. IgG opsonin is the Fc fragment of immunoglobin G; it is the naturally occurring antibody in

the serum that coats the bacteria while the PMNs possess receptors for the same.

2. C3b opsonin is the fragment of complement. It is generated by activation of complement

pathway.

18
Lectins: are carbohydrate binding proteins in the plasma which bind to bacterial cell wall.

B) engulfment stage:

The opsonised particle bound to the surface of phagocyte is ready to be engulfed. This is

accomplished by formation of cytoplasmic pseudopods around the particle due to activation of

actin filaments beneath cell wall, enveloping it in a phagocyte vacuole.

Eventually, the plasma membrane enclosing the phagocytic vacuole breaks from the cell

surface so that membrane lined phagocyte vacuole lies free in the cell cytoplasm. The lysosome

of the cell fuses with the phagocytic vacuole and form phagolysosome or phagosome.

c) Degranulation stage:

The pre-formed granule-stored products of PMNs are discharged or secreted into the

phagosome and the extracellular environment. The specific or secondary granules of PMNS are

discharged (eg; lysosomes) while the azurophilic granules fused with phagosomes. Beside the

discharge of performed granules, mononuclear phagocytes synthesize and secrete certain enzyme

( eg interleukin 2 & 6, TNF), arachdonic acid metabolite (eg; prostaglandins, Leukotrienes),

platelet activating factor) and oxygen metabolites (eg; superoxide oxygen, hydrogen peroxide,

hypochlorus acid).

d) Killings (or) degradation stage:

Now the micro-organisms are killed and digested completing the role of phagocytes as

scavenger cells. The micro-organisms are being killed are digested by hydrolytic enzymes.

However some bacteria like tuberculi bacilli cannot be killed by the mechanism.

The anti- microbial agents be either:

19
1. Oxygen- dependent bacterial mechanism.

2. Oxygen-independent bacterial mechanism.

3. Nitric oxide mechanism.

1) Oxygen dependent bactericidal mechanism: Killing microbial organism by production of

reactive oxygen metabolites (O2, H2O2,, OH, HOCL, HOI, HOBr).

NADH-oxidase present in the cell membrane of phagosome reduces oxygen to superoxide ion.

This super oxide ie; subsequently converted in to H2O2 which has bactericidal properties.

2O2+ 2H+ H2O2.

This is carried out either via enzyme myeloperoxide (MPO) present in the granules of

neutrophils and monocytes or independent of enzyme MPO, as under.-

a) MPO-dependent killing (H2O2- MPO-halide system).

In this mechanism, the enzyme MPO acts on H2O2 in the presence of halides (Cl,I,Br) to

form hypochlorus acid (HOCl,HOI,HOBr) which is more potent antibacterial agent than H2O2:

H2O2 Mpa HOCL+H2O

b) MPO- independent killing- Mature macrophages lack the enzymes MPO & they carry out

bactericidal activity by producing Oh- ions and superoxide singlet oxygen (O) from H2O2 in the

presence of O2 ( Haber-Weiss reaction) or in presence of Fe++ ( Fenton reaction).

20
H2O2 O2 (Haber- Weiss Reaction) OH’

Fe++((Fenton Reaction) OH’

These reactive oxygen metabolites are particularly useful in eliminating microbial

organisms that grow with in phagocytes eg; M.tuberculosis, histoplasma capsulatum.

OXYGEN DEPENDENT ANTI MICROBIAL ACTIVITY

21
2) Oxygen-independent bactericidal Mechanism:-

Some agents released from the granules of phagocytic cells do not require oxygen for

bactericidal activity. These include lysosomal hydrolases, permeability increasing factors,

defensins and cationic proteins.

3) Nitric oxide mechanism:-

No produced by endothelial cells as well as by activated macrophages shown to have

fungicidal and anti- parasitic action but its role in bactericidal activity in human beings is yet not

clear.

NITRIC OXIDE METABOLISM

22
PROCESS OF PHAGOCYTOSIS

23
CHEMICAL MEDIATORS OF INFLAMMATION:

The substances acting as chemical mediators of inflammation may be released from the

cells, the plasma or damaged tissue itself. These are also called as permeability factors or

endogeneous mediators of increased vascular permeability. These classified into:

1. Cell derived mediators.

2. Plasma derived mediators

MEDIATORS OF INFLAMMATION

24
1. Cell derived mediators:

A) Vasoactive amines: Histamines and serotonin are released from mast cells and platelets and

can be identified in early in the course of acute inflammation. Histamine acts mainly on venules

that have H1- Histamine receptors. These cause vasodilation, increased vascular permeability,

itching and pain. Histamine levels decreases rapidly within an hour after the onset of

inflammation.

B) Arachidonic acid metabolites:-

Arachidonic acid is a 20- carbon unsaturated fatty acid found in phospholipids in the cell

membranes of neutrophils, mast cells, monocytes and other cells.

Arachidonic acid must be first activated by stimuli or other mediators like C5a so as to

form arachidonic acid metabolites by 2 pathways, the cycloxygenase pathway and Lipo-

oxygenase pathway.

Cyclooxygenase Pathway:- cyclooxygenase enzyme acts on activated arachidonic acid to form

prostaglandin endoperoxide (PGG2).

PGG2 is enzymatically transformed into PGH2 is further acted upon by enzymes & results in

formation of the 3 metabolites.

a) Prostaglandins (PGD2, PGE2 & PGF2- )

PGD2& PGE2 act on blood vessels to cause increased venular permeability, vasodilation

& bronchodilation and inhibit inflammatory cell function.

PGF2- induces vasodilation and bronchoconstriction.

25
b) Thromboxane A2 (TXA2)- causes vasoconstriction & bronchoconstriction and enhances

inflammatory cell function by causing platelet aggregation.

c) Prostacyclin (PGI2)- induces vasodilation, bronchodilation and inhibits inflammatory cell

function by acting as an anti- aggregator agent for platelets.

Lipoxygenase Pathway:-

The enzyme lipoxygenase acts on arachidonic acid to form hydroperoxy compound, 5-

HPETE which on further peroxidation forms5HETE and leukotrienes.

5HETE I is potent chemotactic agent of neutrophils, leukotrienes are slow acting

substances of anaphylaxis. First the unstable compound LTA4 is formed which dissociates into

LTB4, LTC4, LTD$ and LTE4. LTB4 is chemotactic for phagocytic cells and stimulates

phagocytic cell adherence while LTC4, LTD4&LTE4 have common actions by causing smooth

muscle contraction and there by induce vasoconstriction, bronchoconstriction and increased

vascular permeability.

26
ARACHIDONIC ACID METABOLITES

C). Lysosomal components:-

1. Granules of neutrophils- these are two types- specific or secondary and azurophilic or

primary.

The specific granules contain lactoferrin, lysozymes, alkaline phosphatase and

collagenase while large azurophili granules have myeloperoxidase and hydrolases and neutral

proteases such as elastase, collagenase and proteinase.

Acid proteases act within the cell to cause destruction of bacteria in

phagolysosome while neutral proteases attack on the extracellular constituents such as

basement membrane, collagen, elastin, cartilage by proteases results in harmful tissue destruction

which is controlled by α1—anti trypsin and α2- macroglobulin.

27
2. Granules of monocytes and tissue macrophages:- release acid proteases, collagenase,

elastase and plasminogen activator.

D) Platelet activating factor:- Releasedfrom IgE- sensitized basophils or mast cells, endothelium

and platelets. Its functions are-

- Platelet aggregation and release reaction.

- increased vascular permeability.

- Vasodilation.

- Broncho constriction.

- Adhesion of leukocytes toendothelium.

- Chemotaxis.

E) Cytokines:- these are produced by activation of lymphocytes & monocytes. Main cytokines

acting as mediators of inflammation are- interleukin-1, TNF- and β, interferon (IF)-γ ,

chemokines (IL-8, PF-4)

IL-1 and TNF-α are formed by activated macrophages while TNF- β and IFγ are

produced by activated T cells.

The actions of various cytokines are – IL-1, TNF- , TNF-β: induce increased leukocyte

adherence, thrombogenicity, elaboration of other cytokines, fibroblastic proliferation and acute

phase reactions. IF-γ cause activation of macrophages and neutrophils.

28
F) Nitric oxide and oxygen metabolites: Activated macrophages produce NO during oxidation of

arginine. NO acts as vasodilator, anti-platelet activating agent, and slows microbial action in

inflammation.

Oxygen derived metabolites are superoxide, H2O2, OH and toxic NO products which

cause endothelial damage, increased vascular permeability, activation of proteases and

inactivation of anti-protinase. Causing tissue matrix damage and damage to other cells.

2) Plasma derived mediators:- These include products derived from activation of kinin,

clotting, fibrinolytic and complement system.

Hagmen factor XII) of clotting system plays a key role in interactions of the four system

which are interrelated.

Factor XII is activated to XIIa by contact of the factor leaving through the endothelial

gaps with basement membrane. This activates all the following systems:

a) The Kinin System:- Bradykinin end product of kinin system which induces slow contraction

of smooth muscles, vasodilation and stimulates pain receptors.

First Kallikrein is found from plasma pre- Kallikrein by the action of pre-Kallikrien

activator which is a fragment of factor XIIa. Kallikrein then acts on high molecular weight

kininogen to form bradykinin.

b) The Coagulation cascade: - Factor XIIa initiates the cascade of the clotting system resulting in

formation of fibrinogen which is acted upon by thrombin to form fibrin and fibrinopeptides.

The actions of fibrinopeptides in inflammation are

29
- Increased vascular permeability

- Chemotaxis for leukocytes

- Anti- coagulant activity.

- C) The Fibrinolytic system

- This system is activated by plasminogen activator. The plasminogen activator acts on

plasminogen as component of plasma proteins to form plasmin. Further breakdown of

fibrin by plasmin forms fibrinopeptides or fibrin split products.

o The actions of plasmin in inflammation are-

o activation of factor XII

o Splits complement C3 to form C3a which is a permeability factor.

o Degrades fibrin to form fibrin split products which increase vascular permeability

and are chemotactic to leukocyte.

d) The Complement System:-

The activation of complement system can occur either

- By Classic pathway through antigen- antibody complexes

- By alternate pathway via non- immunologic agents such as bacterial toxins, snake

venoms and IgA.

- Complement system on activation by either of these pathways yield anaphylotoxins C3a,

C4a, C5a and membrane attack complex (MAC). The relative potencies of

anaphylotoxins are in the descending sequence of C3a.C5a.C4a.

30
The action ofanaphylotoxins in inflammation are:-

o Release of histamines from mast cells and basophils.

o Increased vascular permeability causing oedema in tissues.

o C3b augments phagocytosis.

o C5a is chemotactic for leukocytes.

The action of MAC is to cause pores in the cell membranes of invading

micro-organisms.

REGULATION OF INFLAMMATION:-

The onset of inflammatory response may have potential damaging influence on the host

tissues as seen in hypersensitive reactions. The self-damaging effects are controlled by host

mechanism so as to resolve inflammation. These mechanisms are:-

1. Acute phase reactants- These proteins are synthesized mainly in the liver and to some extent in

macrophages. These include-

a. Cellular protein factors - α 1- antitrypsin, α1 chymotrypsin, α2- anti plasmin, plasminogen

activator inhibitor.

b. Coagulation proteins (fibrinogen, plasminogen, von- Williband factor, Factor VII)

c. Transport proteins (ceruloplasmin, haptoglobulin)

d. Immune agents (serum amyloidal and P component C reactive protein)

e. Stress proteins- (Heat shock proteins,)

31
Deficient synthesis of aPR leads to severe form of disease in chronic and repeated

inflammatory response.

2. Corticosteroids – The endogenous glucocorticosteroids act as anti- inflammatory agents.

These levels are raised in infection and trauma by self – regulating mechanism.

3. Free cytokine receptors- These receptors in serum directly related with disease activity.

4. Suppressor T cells- inhibit function of T & B cells.

5. Anti- inflammatory chemical mediators- PGE2 and prostacyclin have both pro- inflammatory

as well as anti- inflammatory actions.

INFLAMMATORY CELLS: The cells participating in inflammation are:

1. Polymorphonuclear neutrophils (PMN)- the granules of neutrophils contain many

substances like protease, myeloperoxidases, lysosome, esterase, aryl sulfatase acid and

alkaline phosphatase and cationic proteins.

The function of neutrophil in inflammation are initial phagocytosis and engulfment. Harmful

effects are destruction of the basement membrane of glomeruli and small blood vessels.

2. Eosinophils: the granules of eosinophils produce variety of enzymes which have bactericidal

and toxic action against helminthic parasites. These granules are rich in myeloperoxidase but

lack lysozyme. In allergic conditions, parasitic infections, skin diseases and certain malignant

lymphomas, the absolute number of eosinophils is increased and take part in inflammatory

response associated with conditions.

32
3. Basophils (mast cells)-these contain coarse basophilic granules, these granules are laden with

heparin and histamine. Basophils have receptors for Ig E and degranulate when cross linked with

antigen. These release histamine, luekotrienes and platelet activating factor in inflammation.

4. Lymphocytes-they have scanty cytoplasm and contain large nucleus. B lymphocytes play a

major role in antibody formation and T lymphocytes in cell mediatedimmunity. These cells

participate in the following types of inflammatory responses.

 In tissues ,they are dominant in chronic inflammation and late stages of acute

inflammation

 In blood, their number is increased in chronic infections like tuberculosis.

5. Plasma cells- They develop from lymphocytes and are rich in RNA and gamma globulin in

their cytoplasm. Their number is increased in conditions such as syphilis, rheumatoid arthritis,

tuberculosis, hyper sensitive states and multiple myeloma. These cells are most active in

antibody synthesis.

6. Giant cells- Giant cells in inflammation are

I. Foreign body giant cells-seen in chronic infective granuloma,leprosy, and tuberculosis.

II. Langhan’s giant cells-seen in tuberculosis and sarcoidosis.

III. Touton giant cells-seen in xanthoma

IV. Aschoff giant cells-seen in rheumatic nodule

33
INFLAMMATORY CELS

34
MORPHOLOGY AND SYSTEMIC EFFECTS OF ACUTE INFLAMMATION

The morphological variants of acute inflammation are

1. Pseudo membranous inflammation

2. Ulcers

3. Suppuration (abscess formation)

4. Cellulitis

5. Bacterial infection of blood such as bacteremia, septicemia, pyaemia

The systemic effects of acute inflammation are

1. Fever

2. Leucocytosis

3. Lymphangitis-Lymphadenitis

4. Shock

35
CHRONIC INFLAMMATION

Chronic inflammation is defined as prolonged process, in which tissue destruction and

inflammation occur at the same time.

Chronic inflammation can be caused by

 Chronic inflammation followed by acute inflammation

 Recurrent attacks of acute inflammation

 Chronic inflammation stating denovo

GENERAL FEATURES OF CHRONIC INFLAMMATION

The general features which are characteristic of any chronic inflammation are

1 .Mononuclear cell infiltration:

Chronic inflammatory lesions are infiltrated by mononuclear cells like phagocytes and

lymphoid cells. phagocytes are represented by circulating monocytes, tissue

macrophages, epitheloid cells and sometimes multi nucleated giant cells. The

macrophages comprise the most important cells in chronic inflammation. These appear at

the site of inflammation from

 Chemotactic factor for macrophages

 Local proliferation

 Long survival of macrophages at the site of inflammation

36
The blood monocytes on reaching the extra vascular space transform in to tissue

macrophages. On activation macrophages release several biologically active substances

such as acid and neutral proteases, oxygen derived reactive metabolites and cytokines.

These production bring about tissue destruction, neovascularization and fibrosis.

Other chronic inflammatory cells include lymphocytes,plasma

cells,esinophills, and mast cells, in chronic inflammation lymphocytes and macrophages

influence each other and release mediators of inflammation.

2. Tissue destruction or necrosis:

This is most common in chronic inflammation and bought about by activated macrophages by

release of a variety of biologically active substances.

Proliferative changes:

As a result of necrosis,proliferation of small blood vessels and fibroblasts is stimulated resulting

in formation of inflammatory granulation tissue. Eventually, healing by fibrosis and collagen

laying takes place.

TYPES OF CHRONIC INFLAMMATION

1. Chronic nonspecific inflammation-It is characterized by nonspecific inflammatory cell

infilteration.eg- Chronic osteomyelitis, lung abscess.

A variety of this type of chronic inflammatory response is chronic suppurative

inflammation in which infiltration by polymorphs and abscess formation are additional

features.eg-Actinomycosis

2. Chronic granulomatous inflammation-It is characterized by formation of granuloma

37
Eg-Tuberculosis,leprosy,syphlisis,actinomycosis,sarciodosis

DIFFERENCES BETWEEN ACUTE AND CHRONIC INFLAMMATION

38
WOUND HEALING

Injury to tissue may lead to cell death and tissue destruction. Healing is the body response

to injury in an attempt to restore normal structure and function. This involves two distinct

processes.

 Regeneration when healing takes place by proliferation of parenchymal cells and

usually results in complete restoration of original tissues

 Repair when the healing takes place by proliferation of connective of connective

tissue elements resulting in fibrosis and scarring.

Healing of skin wounds provides a chemical example of combination of repair and regeneration

This can be accomplished in one of the following two types

 Healing by first intention (primary union)

 Healing by second intention(secondary union)

Healing by first intention (primary union)-

The sequence of events in primary union are

1 .Initial hemorrhage -Initially incised wounds are filled with blood

2.Acute inflammatory response-starts with in 24 hrs. With appearance of

polymorphs

3.Epithelial changes-scab formation

4. Organization-fibroblasts invade and new collagen fibrils start forming

5. Suture tracts-sutures are removed after 7 days and the suture track is avulsed

39
Healing by secondary intention(secondary union)

This is defined as healing of wound open with a large tissue defect and

wound cannot be approximated by surgical sutures but is left open. The sequel of events are

1. Initial hemorrhage- Wound space filled with blood

2. Inflammatory phase- appearance of macrophages

3. Epithelial changes- scab formation

4. Granulation tissue formation-Formed by proliferation of fibroblasts

5. Wound contraction-due to action of myofibroblasts

HEALING BY PRIMARY AND SECONDARY INTENTION

40
COMPLICATIONS OF WOUND HEALING

During the course of healing following complications can occur

 Infection of wound

 Implantation cyst

 Pigmentation

 Deficient scar formation

 Incisional hernia

 Hypertrophied scars and keloid formation

 Excessive contraction

 Neoplasia

41
FACTORS INFLUENCING HEALING

A.LOCAL FACTORS

1. Infection

2. Poor blood supply

3. Foreign bodies

4. Movement

5. Exposure to ionizing radiation

6. Exposure to ultra violet light

B.SYSTEMIC FACTORS

1. Age

2. Nutrition

3. Systemic infection

4. Administration of glucocorticoids

5. Uncontrolled diabetics

6. Hematologic abnormalities

42
HEALING OF FRACTURES:

Healing of fractures can be considered in many stages, in fact it is continuous and different

stages overlap in different areas

1. Hematoma formation

2. Inflamatory reaction:

3. Organization of granulation tissue:

4. Formation of provisional callus: (Latin – hard).

5. Formation of definitive callus:

1. Hematoma formation:

Due to torn blood vessels. The broken fragments may further damage soft tissues. Hematoma

holds the fragments together loosely through fibrin network.

2. Inflamatory reaction:

Hyperemia of the reaction causes decalcification of bone adjacent to the fracture.

Macrophages phagocytose red cells and debris of soft tissues.

Resorption of necrosed bone is a slow process, it is executed through osteoclasts and is helped

by acid pH which develops in the area.

43
3. Organization of granulation tissue:

Granulation tissue originates from soft tissues of bone (marrow, endosteum and periosteum)

and from soft tissues around fractured bone.

4. Formation of provisional callus: (Latin – hard).

Is hard calcified granulation tissue uniting the fractured ends. The formation begins between

6th and 10th day.

 The main contribution comes from the undamaged cells of the periosteum& endosteum.

 Formation of nonlamellar bone:

 Follows intra-membranous ossification.

 Osteoid laid by osteoblasts subsequently

 get calcified.

 Calcification is helped by alkalinity of tissues,

 alkaline phosphatase secreted by osteoblasts ,local

 super saturation of calcium derived by resorption of

 bony spicules.

 Bony callus predominates whenever fracture

 segments are properly immobilized.

44
 Formation of cartilage:

 The process is same as endochondral ossification.

 Cartilage formation occurs prominently in superficial part of callus.

 Greater the movement of fractured fragments or their separation, larger the amount of

cartilage formed.

 Provisional callus is completely formed in 2 to 3 weeks.

HEALINGOF AN EXTRACTED SOCKET

The healing of an extracted socket occurs as in secondary intention. The stages are

1.Initial hemorrhage

2. Inflammatory phase

3. Epithelial changes

4. Granulation tissue formation

5. Pro callus formation or woven bone formation

6. Osseous callus formation

7. Remodeling

45
REFERENCES

1.Mrinali sant, Text book of pathology,2nd edition, Central publishers.

2. T.K Dey Text book of general pathology,15th edition, Central publishers.

3. Harsh Mohan, Essentials of pathology, 5th edition, Jaypee publishers.

4.JCE Underwood, General and systemic pathology, 4th edition, Churchill livingston publications

5.Cortan kumar Robins, Basic pathology ,6th edition, Saunders publications

6. Anderson, Text book of pathology, 10th edition. CRC Press publications.

7. S.M Balaji, Text book of oral and maxillofacial surgery, 2nd edition,Elesiver publications

46