Date post: | 30-Oct-2014 |
Category: |
Documents |
Upload: | drgurinder-kanwar |
View: | 127 times |
Download: | 5 times |
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
1
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.
.
2
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
3
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.
4
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.
5
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
6
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.
7
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
8
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.
9
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
10
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.
11
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).
12
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.
13
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.
14
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 :
15
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.
16
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
17
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.
18