DEPARTMENT OF PERIODONTOLOGY AND ORAL IMPLANTOLOGY

SWAMI DEVI DYAL HOSPITAL AND DENTAL COLLEGE,BARWALA

SEMINAR ON

INFLAMMATION

Presented by : Dr.Prabhjot Kaur

CONTENTS:

1. Introduction

2. Agents causing inflammation

3. Types of inflammation

4. Acute inflammation

5. Events in acute inflammation

6. Chemical mediators of inflammation

7. Inflammatory cells

8. Factors determining variation in inflammatory response

9. Morphology of acute inflammation

10.Systemic effects of acute inflammation

11.Fate of acute inflammation

12.Chronic inflammation

13.General features of chronic inflammation

14.Types of chronic inflammation

15.References

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INTRODUCTION

The word inflammation is derived from Latin word enflammare, which

means the state of being inflamed. Inflammation is fundamentally a protective

response whose ultimate goal is to get rid of the organism of both the initial

cause of cell injury and consequences of such injury, the necrotic cells and

tissue. Without inflammation infections would go unchecked, wounds would

never heal and injured organs might remain permanent festering sore.

However, inflammation and repair may be potentially harmful.

It can be defined as local response of living mammalian tissues to injury due to

any agent. Its body’s defense reaction in order to eliminate or limit spread of

injurious agent.

According to Robbins, it’s a protective response intended to eliminate the

initial cause of cell injury as well as necrotic cells and tissues resulting from

original insult.

Inflammation is divided into acute and chronic patterns. Acute

inflammation is of relatively short duration lasting for minutes, several hours or

a few days and its main characteristics are exudation of fluid and plasma

proteins and emigration of leukocytes predominantly neutrophils.

Chronic inflammation on other hand is of longer duration and is

associated histologically with presence of lymphocytes and macrophages and

with the proliferation of blood vessels and connective tissue.

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AGENTS CAUSING INFLAMMATION:

The agents leading to inflammation may be classified as ;

1) Physical agents like heat, cold, radiation, mechanical trauma.

2) Chemical agents like organic and inorganic poisons.

3) Infective agents like bacteria, viruses and their toxins.

4) Immunological agents like cell mediated and antigen antibody reactions.

Inflammation involves 2 basic processes with some overlapping viz

early inflammatory response and later followed by healing. Through both these

processes generally have protective role against injurious agent’s they may

cause considerable harm to the body as well.

TYPES OF INFLAMMATION:

Inflammation can be broadly classified as :A). acute inflammationb). sub acute inflammationc). chronic inflammation.

ACUTE INFLAMMATION :

The changes in acute inflammation can be conveniently described under

2 headings.

I. Vascular events

II. Cellular events

I. Vascular Events :

Alteration in the microvasculature is the earliest response to tissue

injury. These include ;

a) Hemodynamic changes

b) Changes in vascular permeability

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Hemodynamic Changes :

These results from changes in the vascular flow caliber of small blood

vessels in injured tissue. The sequence is ;

1) Transient vasoconstriction of arterioles with mild form of injury. Blood

flow is reestablished in 3-5 seconds while with more severe injury the

vasoconstriction may last for about minutes.

2) Next follows persistent progressive vasodilatation which involves

mainly the arterioles, the change is obvious with in half an hour of

injury. Vasodilatation results in increased blood volume in

microvascular beds of the area which is responsible for redness and

warmth at the site of acute inflammation.

3) Progressive vasodilatation in turn elevate the local hydrostatic pressure

resulting in transudation of fluid into the extracellular space. This leads

to swelling at the local site of acute inflammation.

4) Slowing of stasis of microcirculation occurs and is attributed to

increased permeability of microvasculature that result sin increased

concentration of red cells and thus raised blood viscosity.

5) Stasis or slowing is followed by leucocytic margination or peripheral

orientation of leucocytes mainly neutrophil along the vascular

endothelium. The leucocytes stick to the vascular endothelium briefly

and then move and migrate through the gaps between the endothelial

cells into extravascular space. This process is known as emigration.

The features of haemodynamic changes in inflammation are best

demonstrated by the Lewis equipment by stroking inner aspect of forearm by a

blunt point. The reaction so elicited is known as triple response or red line

response consisting of ;

1) Red line : Appears in a few seconds from vasodilation of capillaries and

venules.

2) Flare : Is the bright reddish appearance or flush surrounding the redline

and results from vasodilatation of adjacent arterioles.

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3) Wheal : Is the swelling or oedema of the surrounding skin occurring due

to transduation of fluid into extravascular space.

ALTERED VASCULAR PERMEABILITY :

Pathogenesis : In and around the inflamed tissue there is accumulation of

oedema fluid in the interstitial compartment which comes from blood plasma

by its escape through the endothelial wall of peripheral vascular bed. In the

initial stage, the escape of fluid is due to vasodilatation and consequent

elevation in hydrostatic pressure. This is transudate in nature. (Filtrate of blood

plasma without changes in endothelial permeability and is a character of non

inflammatory edema). But subsequently the characteristic inflammatory

oedema, exudates appears by increased vascular permeability of

microcirculation. The appearance of inflammatory oedema due to increased

vascular permeability of microvascular bed is explained on the basis of

Starling’s hypothesis. In normal circumstances, the 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.

Forces that causes inward movement of interstitial fluid into circulation are

intravascular osmotic pressure and hydrostatic pressure of interstitial fluids.

Whenever little fluid is left in the interstitial compartment is drained

away by lymphatics and thus no oedema results normally. However in

inflamed tissues, the endothelial lining of microvasculature becomes more

leaky. Consequently intravascular osmotic pressure decreases and osmotic

pressure of the interstitial fluid increases resulting in excessive outward flow of

fluid into the interstitial compartment which is exudative inflammatory

oedema.

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CELLULAR EVENTS :

The cellular phase of inflammation consists of 2 processes.

1) Exudation of leucocytes

2) Phagocytosis

1) Exudation of Leucocytes :

The escape of leucocytes from the lumen of microvasculature to the

interstitial tissue is the most important feature of inflammatory response. In

acute inflammation polymorphonuclear neutrophils comprise the first line of

body defense, followed later by monocytes and macrophages.

The changes leading to migration of leucocytes are as follows.

1) Changes in the formed elements of blood :

Normal axial flow consists of central stream of cells comprises by

leucocytes and RBC and peripheral cell free layer of plasma close to vessel

wall. Due to slowing and stasis the central stream of cells widens and

peripheral plasma zone becomes narrower because of loss of plasma by

exudation. This phenomenon is known as margination.

As a result of this redistribution, the neutrophils of the central column

come close to the vessel wall, this is known as pavementing.

2) Adhesion or Rolling :

Peripherally marginated and pavemented neutrophils stick briefly to the

endothelial cells lining the vessel walls or roll over it.

Injury leads to neutralization of the normal negative change on

leucocytes and endothelial cells so as to cause adhesion. This phenomenon of

loose and transient adhesion between endothelial cells and leucocytes and later

tight adherence of the leucocytes and later tight adherence of the leucocytes to

the vascular endothelium is brought about by 4 types of distinct adhesion

molecules ;

1) Selectins

2) Adressins

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3) Integrins

4) Immunoglobulin super family adhesion molecule

3) Emigration :

After sticking of neutrophils endothelium, the former move along the

endothelial surface and throw out cytoplasmic pseudopods. Subsequently the

neutrophils lodged between the endothelial cells and basement membrane cross

the basement membrane by damaging it locally with secreted collageases and

escape out into extravascular space this is known as emigration.

4) Chemotaxis :

The chemotactic factor mediated transmigration of leucocytes after

crossing several barriers (endothelium, basement membrane, and matrix) to

reach the interstitial tissue is called chemotaxis. The agents acting as potent

chemotactic substances for different leucocytes called chemokines are as

follows ;

i) Leukotriene B4 (LTB4)

ii) Platelet factor 4

iii) Components of complement system

iv) Cytokines

v) Soluble bacterial products (such as formylated peptides).

vi) Chemotactic factor for CD4 + T cells

vii) Exotoxin chemotactic for eosinophils

In addition chemotactic agents also induce leucocyte activation that

includes, the production of arachidonic acid metabolites. Degranulation and

secretion of lysosomal enzymes generation of O2 metabolites, increased

intracellular calcium and increase in leucocyte surface of adhesion molecules.

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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 2 main types of phagocytic cells.

i) PMNs which appear early in acute inflammatory response, also

called microphages.

ii) Circulating monocytes and fixed mononuclear phagocytes called as

macrophages.

The process of phagocytosis is similar for both polymorphs and

macrophages and involves the following 4 steps ;

1) Attachment stage (Opsonization)

2) Engulfment stage

3) Secretion (degranulation stage)

4) Killing or degradation stage

1) Attachment Stage :

The phagocytic cells as well as microorganisms to be ingested have

usually negatively charged surface and thus they repel each other. In order to

establish a bond between bacteria and the cell membrane of phagocytic cell, the

micro-organisms get coated with opsonins which are naturally occurring

factors in serum. The two main opsonins present in serum and their

corresponding receptors on the surface of phagocytic cells are IgG opsonin and

C3b opsoin.

2) Engulfment Stage :

The opsonised particle bound to the surface of the phagocyte is ready to

be engulfed. This is accompanied by the formation of cytoplasmic pseudopods

around the particle enveloping it in a phagocytic vacuole. Eventually the

plasma membrane enclosing the pahgocytic vacuole breaks from the cell

surface so that membrane lined phagocytic vacuole lies free in the cell

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cytoplasm. The lysosomes of the cell fuse with the phagocytic vacuole and

forms phagocytosome or phagosome.

3) Secretion (Degranulation) Stage :

During this process the performed granule stored products of PMN’s are

discharged or secreted into the phagosome and the extracellular environment.

In particular the specific or secondary granules of PMNs are discharged (eg.

Lysosomes). While the azurophilic granules are fused with phagosomes

besides the discharge of preformed granules, mononuclear phagocytes

synthesis and secrete certain enzyme (eg. INL2 and 61 TNF). Arachidonic acid

metabolites (Eg. Prostaglandins, Leukotrienes, Platelet activating factor) and

O2 metabolites.

4) Killing or Degradation :

Next comes the stage of killing and digestion of microorganism

completing the role of phagocytes as scavenger cells. The microorganisms

after being killed by antibacterial substances are degraded by hydrolytic

enzymes. However this mechanism fails to kill and degrade some bacteria like

tubercle bacilli.

Mechanisms :

1) O2 dependent bactericidal mechanism.

2) O2 independent bactericidal mechanism

3) Nitric oxide mechanism

CHEMICAL MEDIATORS OF INFLAMMATION :

Also called as permeability factor or endogenous mediators of increased

vascular permeability, these are a large and increasing number of endogenous

compounds which can enhance vascular permeability.

However currently many chemical mediators have been identified with

partake in other processes of acute inflammation as well.

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The substance acting as chemical mediators of inflammation maybe

released from the cells, the plasma or damaged tissue itself.

They are broadly classified into 2 groups.

1) Mediators released by cells.

2) Mediators organization from plasma.

Chemical Mediators of Acute Inflammation :

I. Cell derived

1. Vasoactive amines (Histaine, 5 hydroxy tryptamine).

2. Arachidonic acid metabolites.

i) Metabolites via cycloxygenase pathway (Prostaglandins,

thromboxane A2, prostacyclin).

ii) Metabolites via lipoxygenase pathway (Leukotrienes)

3. Lysosomal components

4. Platelet activating factor

5. Cytokines (IL1, TNF-, TNF-, Chemokines).

II. Plasma derived mediators (Plasma proteases).

There are products of:

1) Kinin system

2) Clotting system

3) Fibrinolytic system

4) Complement system

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Chemical mediators involved in causing increased vascular permeability

Source Mediator Main actionMast CellsBasophils, Platelets

HistamineSerotonin

permeability Permeability

Cell derivedPlateletsInflammatory cells Lysosomal enzymes Tissue damage

Platelet activating factor

permeability

Prostaglandins VasodilationLeucotrienes permeabilityCytokines FeverNitric oxide and O2 metabollites

Tissue damage

Clotting and fibrinolytic system

Fibrin split products permeability

Plasma derived

Kinin system Kinin/bradykinin permeability

Complement system Anaphylaxis C3a, C4a, C5a

permeability

INFLAMMATORY CELLS :

1) Polymorphonuclear neutrophils (Neutrophils or polymorphs).

Functions :

A) Initial phagocytosis of microorganisms as they form first line of body

defense in bacterial infection.

B) Engulfment of antigen antibody complex and non microbial material.

C) Harmful effect of neutrophils is destruction of basement membrane of

glomeruli and small blood vessels.

2) Eosinophils :

Contains a variety of enzymes of which the major basic protein and

eosinophilic cationic protein are the most important granules which have

bactericidal and toxic action.

High levels of steroid hormones leads to fall in number of eosinophils

and even disappearance from blood.

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Their increase occurs in following conditions and takes part in

inflammatory reaction.

1) Allergic conditions

2) Parasitic conditions

3) Skin diseases

4) Certain malignant lymphomas

Basophils :

In immediate and delayed type of hypersensitivity reaction and release

of histamine by IgE sensitized basophils.

Lymphocytes :

Besides their role in antibody formation and in cell mediated immunity

these cells participate in following inflammatory responses.

1) In tissues, they are dominant cells in chronic inflammation and late stage

of acute inflammation.

2) In blood, their number is increased in chronic infectious like

tuberculosis.

Plasma Cells (Develops from lymphocytes)

Most active in antibody synthesis. Their number is increased in

1) Prolonged infection with immunological responses. Eg. Syphilis,

Rheumatoid arthritis and T.B.

2) Hypersensitivity states

3) Multiple myeloma

Mononuclear Phagocyte Cells / Macrophages :

Functions :

1) Phagocytosis and pinocytosis (cell drinking).

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2) These on activation by lymphokines or by non immunologic stimuli

elaborate a variety of biologically active substances like proteases,

plasminogen activator etc.

FACTORS DETERMINING VARIATION IN INFLAMMATORY

RESPONSES :

Although acute inflammation is typically characteristic by vascular and

cellular events with emigration of neutrophils, not all are characteristic by same

for Example, Typhoid fever is an example of acute inflammation but the

cellular response in it is lymphatic.

Morphologic variations in inflammation depends upon a number of

factors and process.

I. Factors Involving Organisms :

1) Type of injury and infection. Eg. Skin reacts to herpes by formation of

vesicle.

2) Virulence of species.

3) Dose : Concentration of organism in small doses produces local

infection. While larger dose results in more severe spreading infections.

4) Portal of entry : Some organisms are infective only if administered by

particular route. Eg. Vibrio cholesal is not pathogenic if injected

subcutaneously but cause cholera if swallowed.

5) Product of organism : Some produce enzyme that helps in spread of

infection. Eg. Hyaluronidase Cl.welchi.

II. Factors involving the host

1) General health of host – poor health renders host more prone.

2) Immune state of host.

3) Leukaemia

4) Site or type of tissue involved

5) Local host factors – Ischemia, Presence of foreign body chemicals cause

necrosis and are harmful.

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III. Types of exudation :

Serous : when fluid exudates resembles serum, or in watery. Eg. Pleural

effusion in TB and blister formation in burns.

Fibrinous : When fibrin content of the fluid exudates is high. Eg.

Pneumococcal infections.

Purulent or supportive exudates in formation of pus as seen in infection

with pyogenic bacteria. Eg. Abscess.

Haemorrhagic : When there is vascular damage. Eg. Acute hemorrhagic

pneumonia in influenza.

Catarrhal : When the surface inflammation of epithelium produces

increased secretion of mucous. Eg. Common cold.

IV. Cellular Proliferation : Variable cellular proliferation is seen in different

types of inflammation.

1) No significant cellular proliferation in acute bacterial infections except

in typhoid fever.

2) Viral infections have ability to stimulate cellular proliferation. Eg.

Epidermal cell proliferation in herpes simplex.

3) Chronic inflammation cellular proliferation of macrophages, fibroblasts

and endothelial cell occurs.

V. Necrosis :

The extent and type of necrosis in inflammation is variable.

In gas gangrene there is extensive necrosis with discolored and foul

smelling tissues.

In chronic inflammation such as TB, there is characteristic of caseous

necrosis.

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MORPHOLOGY OF ACUTE INFLAMMATION :

1) Pseudomembraneous inflammation : Inflammatory response of mucous

surface. As a result of denudation of epithelium, plasma exudes on

surface, it coagulates forms false membrane that gives this type of

inflammation its name.

2) Ulcer : Local defects on surface of organ by inflammation.

3) Suppuration : In which acute bacterial infection is accompanied by

intense neutrophilic infiltrate in inflamed tissue it results in tissue

necrosis. A cavity is formed (abscess) that contains purulent exudates.

4) Cellulitis : Is diffuse inflammation of the tissues resulting from

spreading effects of substances like hyaluronidase released by some

bacteria.

SYSTEMIC EFFECTS OF ACUTE INFLAMMATION :

1) Fever : Occurs due to bacteremia mediated through prostaglandin IL-1,

TNF.

2) Leucocytosis : Commonly accompanied the acute inflammatory

reactions, usually of the range of 15,000 – 20,000/l. When counts are

higher than this with shift to left of myeloid cells leukemoid reaction

occur.

3) Lymphangitis : Lymphadenitis is one of the important manifestation of

localized inflammatory injury. The lymphatics and lymph nodes that

drain the inflamed tissue show reactive inflammatory changes in the

form of lymphangitis and lymphadenitis.

4) Shock : May occur in several cases. Massive release of cytokines TNF-

, a mediator of inflammation in response to severe tissue injury or

infection results in profuse systemic vasodilation, increased vascular

permeability and intravascular volume loss and causes shock.

Fate of Acute Inflammation :

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The acute inflammatory process can culminate in one of the following 4

outcomes.

1) Resolution

2) Healing by scarring

3) Progression to suppuration

4) Progression to chronic inflammation.

Resolution: It means complete return to normal. This occurs when tissue

changes are slight and the cellular changes are reversible. Eg. Resolution of

lobar pneumonia.

Healing by Scarring : This takes place when the tissue destruction in acute

inflammation is extensive so that there is no tissue regeneration but actually

there is healing by fibrosis.

Suppuration : When the pyogenic bacteria causing acute, inflammation result in

severe tissue necrosis, the process progresses to suppuration.

Chronic Inflammation : The acute inflammation may progress to chronic

inflammation.

CHRONIC INFLAMMATION :

Definition and Causes :

Chronic inflammation is defined as prolonged process in which tissue

destruction and inflammation occur at the same time.

Chronic inflammation can be caused by one of the following 3 ways ;

1) Chronic inflammation following acute inflammation. Eg. Osteomyelitis,

pneumonia.

2) Recurrent attacks of acute inflammation. Eg. Recurrent urinary tract

infection leading to chronic pyelonephritis.

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3) Chronic inflammation starting denovo eg. Infection with mycobacterium

TB.

GENERAL FEATURES OF CHRONIC INFLAMMATION :

1) Mononuclear Cell Infiltration :

Chronic inflammatory lesions are infiltrated by mononuclear

inflammatory cells like phagocytes and lymphoid cells. Phagocytes are

represented by circulating monocytes, tissue macrophages, epitheloid cells and

sometimes multinucleated giant cells. Other chronic inflammatory cells

include lymphocytes, plasma cells, eosinophils and mast cells. The

macrophages comprise with most important cells in chronic inflammation

from ;

a) Chemotactic factors for macrophages.

b) Local proliferation of macrophages

c) Longer survival of macrophages at the site of inflammation.

2) Tissue destruction or Necrosis :

Are common in many chronic inflammatory lesions and are brought

about by activated macrophages by release of a variety of biologically active

substances.

3) Proliferative changes :

As a result of necrosis, proliferation of small blood vessels and

fibroblasts is stimulated resulting information of inflammatory granulation

tissue. Eventually healing by fibrosis and collagen laying takes place.

TYPES OF CHRONIC INFLAMMATION :

Conventionally chronic inflammation is subdivided into 2 types ;

1) Non specific, 2) Specific

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Non-specific : When irritant substance produces a non specific chronic

inflammatory reaction with formation of granulation tissue and healing by

fibrosis. Eg. Chronic osteomyelitis, chronic ulcer.

Specific : When the injurious agents causes a characteristic histologic tissue

response. Eg. T.B., Leprosy, syphilis. However for more descriptive

classification histologic features are used that are 2 types ;

1) Chronic non specific inflammation is characterized by nonspecific

inflammatory cell infiltration.

2) Chronic granulomatous inflammation on characterized by formation of

granulomas. Eg. Tuberculosis, leprosies, syphilis, actinomycosis,

sarcoidosis etc.

Granuloma is defined as a circumscribed tiny lesions about 1 mm in

diameter. Composed preaminonantly of collection of modified macrophages

called epithelioid cells and rimmed at the periphery by lymphoid cells.

REFERENCES :

1. General Pathology – Robbins

2. Essentials of Oral Pathology – Shafer and Hine, 4th

Edition.

3. Pathology for Dental Students – Harshmohan, 2nd

Edition.

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