INFLAMMATION

Definition:
Inflammation is defined as a local response of living mammalian
tissue to an 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.

Inflammatory Agents:
Physical Agents:

like hot, cold, radiation, and mechanical

trauma

Chemical Agents:

like organic and inorganic poisons

Infective Agents:

bacteria and fungi and their toxins

Immunological Agents: cell mediated and antigen antibody reaction

Infection:
Entry of harmful microbes in to the body and their resultant ill
effect by toxins

Inflammation:
Protective mechanism of the body

Sign of Inflammation:
Four cardinal sign of inflammation are
1.

RUBOR (Redness)

2.

TUMOR (Swelling)

3.

CALOR (Heat)

4.

DOLOR (Pain)
Later a 5 th Sign

5.

FUNCTIO LAESA (Loss of function)

Earlier inflammation was referred to as burning but now we

know burning is only one sign of inflammation.

Types of Inflammation:
Depending upon the host defence. Capacity and duration of
response inflammation is classified into
1.

Acute inflammation

2.

Chronic inflammation

Acute:
It is of short duration and represents early body reaction and is
usually followed by repair.
Chronic:
It is of longer duration and occurs when either the causative
organism of acute inflammation persists for longer time or a stimulus
is such that it induces chronic inflammation from beginning.
2

Acute inflammation
Can be described under
1.

Cellular events &

2.

Vascular events

Vascular Events:
Alteration in microvasculature is the earliest response to tissue
injury. Early signs include
1.

Haemodynamic changes

2.

Change in vascular permeability

Haemodynamic Changes
Irrespective of type of injury immediate vascular response is of
1.

Transient vasoconstrictor of arterioles with mild injury blood

flow is reestablished by 2-3 seconds while in severe injury it
may last for 5 minutes.

2.

Next follows persistent progressive vaso-dilation mainly in the

other microvasculature mechanisms are less affected. This is
seen after half an hour of injury. Vasodilation results in
increased blood in the micro vascular bed of the area, which is
responsible for warmth and redness at the site of injury.

3.

As a result of Vasodilation there will be increased blood volume,

which in turn results in elevation of the local hydrostatic
pressure that results in transduction of fluid into extra cellular
space results in odema.
3

4.

Slowing or stasis slowing results in increase permeability of

microvasculature, which results in increased concentration of
red cells as a result, raised blood viscosity.
5. Leucocytic Margination Leucocyte margination along the
endothelial cells into extra vascular space. This process is
known as Emigration.

Altered vascular permeability

The initial reaction brings around vasodilation which increases
the blood volume in microvasculature blood which leads to increased
hydrostatic pressure, which in turn leads to transudation of fluid into
extra cellular space. This is transuduate in nature, but subsequently the
characteristic inflammatory odema, exudate appears by increase in the
vascular permeability of microcirculation
These changes in vascular permeability can be explained by
Starlings hypothesis.

In normal circumstances the fluid balance is

maintained by two opposing type of Forces.

Forces that cause outward movement

Intra

vascular

hydrostatic

pressure
From microcirculation

Osmotic pressure of interstitium

Forces that causes inward movement

Osmotic intra vascular

pressure and hydrostatic
interstitial pressure

Whatever little fluid left in the interstitial compartment is drained

away by lymphatics.
In case of odema the endothelial lining of microvasculature
becomes more leaky. Intra vascular osmotic pressure decreases and
osmotic pressure in interstitial fluid increases leading to outward flow
of

fluid

into

the

interstitial

compartment

which

is

exudate

inflammatory odema.
Mechanism of Increased vascular permeability:
How the non-permeable endothelial layer of microvasculature
becomes leaky is explained by?
1.

Contraction of Endothelial cells:

Most commonly seen in veins
Due to contraction of endothelium, small gaps occur in
between them resulting in vascular leakiness.
This is a reversible process of short duration (15-30 mins)
Mediated by release of Bradykinin, histamine and other
chemical mediator

 Example of immediate transient leakage is thermal injury

of forearm.
Retraction of Endothelial cells:
There is re-organisation of the endothelial cells that causes
reversible retraction at intercellular junctions. This change also is seen
only in venules and mediated by cytokines. Such as interleukin-1 and
tumour neckrosis factor.

It takes 4-6 hours after injury and last for 24 hours.

E.g. is seen in Invitro experiments only
Direct injury to endothelial cells
Injury to the endothelial cells causes cell necrosis and physical
gap at sites of detached endothelial cells.

This occur in arteries, veins and in capillaries

Increased permeability may be seen immediately after injury and
last for several hours and days (immediate sustained leakage)
Sometimes it may occur after delay of 2-12 hours and last for
days (delayed sustained leakage)
E.g. of immediate sustained leakage are severe bacterial infection
E.g. of delayed sustained leakage are moderate thermal injury and
radiation injury.
Endothelial injury mediated by leucocytes

Leucocytes, which are adhering to the endothelial lining, get

activated.

These activated leucocytes produce proteolytic enzyme and toxic

oxygen species, which causes endothelial injury, and increased
vascular permeability. These vascular leakiness is a late response
e.g. in pulmonary venules and capillaries.

Other Mechanisms
Newly formed capillaries during the process of repair also
possess excessive leaky cells. Vesicles and vacuoles in the cytoplasm
of the endothelial cells of blood vessels, tumor may also account for
leakage of fluid across cytoplasm. (E.g.) healing.

Increased vascular permeability

Mechanism
1.

Endothelial

Microvasculature
Venules

cell

Response

Pathogenesis

Example

Type
Immediate

Histamine,

Mild

transient

Bradykinin

injury

Somewhat

IL 1, TNF

In Vitro only

thermal

contraction
2.

3.

Endothelial

Venules

cell

delayed

retraction

prolonged

Direct

Immediate

endothelial
cell injury

Venules,

arteriole,

capillaries

prolonged

but
Severe burn,
Cell
or

necrosis

and detachment

delay

bacterial infection
radiation injury
Pulmonary

prolonged
4.

Leucocytes

Venules and

mediated

capillaries

endothelial

Delayed
prolonged

injury

Leucocytes

Venules

activation

capillaries

and

5.

All levels

Other

Any type

Healing, tumor
Neovascularisation
transcytosis

Cellular Events
Cellular phase of inflammation includes 2 processes

1.

1.

Exudation of leucocytes and

2.

Phagocytosis

Exudation of leucocytes from the lumen into the interstitial cell

tissue is the most important feature of inflammatory response.

In case of acute inflammation polymorphonuclear neutrophils

forms the first degree of body defence followed by monocytes and
macrophages.

The changes leading to migration of leucocytes are

1.

Change in the formed elements

In the initial stage of inflammation there will be vasodilatation

resulting in increased blood flow followed by stasis, resulting in the

change in the normal axial flow of blood.
Normal axial flow of blood consists of central column of cells
comprised by leucocytes as RBCs and peripheral zone of cell free
plasma. Due to stasis the central zone widens and peripheral plasma

zone becomes narrower due to this loss of plasma occurs by

exudation. This phenomenon is known as Margination.

As a result of this neutrophils of the central column comes close

to the vessel wall. This is known as pavementing.
2. Adhesion and Rolling
The neutrophils get stuck to the endothelial cells lining the
vessel and roll over it. As a result of injury the negative charges of the
leucocytes and endothelial cells gets neutralize resulting in the
adhesion between them.
The adhesion between the leucocytes and endothelial cell is
mediated by glycosylated protein and selection group of surface
receptors
E Selection Endothelial surface
L Selection

- Leucocytes surface

3. Emigration
The neutrophils which are adherent to the endothelium moves
until a suitable site between the endothelial, cells where the
neutrophils throw the pseudopods.

Subsequently the neutrophil is lodged between the basement

membrane and endothelial cells.

They destroy the basement membrane and come out by secretary

collagenase and escape into extra vascular space. This is known as
emigration. The damaged cell is repaired immediately.

Neutrophils are the dominant cells in the inflammatory exudates

in first 24 hours, monocytes and macrophages appear next (24-48
hours).

The

neutrophils

are

short

lived

but

monocytes

and

macrophages survives longer period.

Along with the escape of leucocytes RBC escapes through the

gap between endothelial cell and this is known as Diapedesis.
Diapedesis gives hemorrhagic appearance to inflammation.

Chemotaxis:

10

The transmigration of leucocytes through several barriers into

interstitial tissue is aided by certain chaemotactic factors called
chemotaxis.

Well illustrated by Boydens chamber experiment. In this a

Millipore filter separates the leucocytes solution from the test
solution. If the test solution in a tissue cellular chamber contain
chemotaxis agent, the leucocytes migrate through the pores towards
the chemotaxis agents.
Chemotatic agents are known as chemokines are
1.

Leukotriene B 4 (LTB 4 )

2.

Platelet factor 4

3.

Components of complementary system

4.

Cytokinase

5.

Monocyte chemo attractant protein

6.

Chemotatic factor for CD 4 + T cells

Phagocytosis
It is defined as the process of engulfying the solid particulate
materials by the cell. The cells performing this are phagocytes. The
two types are,

1.

PMNs which appear early in acute inflammation and are

known as microphages.

11

2.

Circulating monocytes and fixed tissue and mononuclear

phagocytes called macrophages.

Steps involved are,

1.

Attachment stage (Opsonisation)

2.

Engulfment stage

3.

Secretion (degranulation) stage

4.

Killing or degradation stage

Attachment Stage:
Usually the phagocyte cell as well as microorganisms has the
same charge hence they repel. The microorganism gets coated with
opsonins, which are naturally occurring factors in serum.
The two main opsonins present in the serum and their
corresponding receptors on the surface of phagocyte cells are
1. IgG opsonins: Corresponding

receptor

on

polymorphs

and

macrophages is FC fragment of immunoglobin.

2. C 3 b opsonin: C 3 b receptor

Engulfment:
Once the microorganisms get attached to the phagocyte cell,
they are engulfed by formation of cytoplasmic pseudopods around the
particle enveloping it, in a phagocytic vacuole. The plasma membrane
of the phagocyte breaks, as a result phagocyte vacuoles lie free in cell
cytoplasm. The lysosome of the cell fuses with the phagocyte vacuoles
and form phagosomes.

12

Secretion:
During this process of engulfment, degeneration of monocytes
and macrophages take place, resulting in the liberation of certain
hydrolytic enzyme and anti bacterial substances.
Killing or degradation:
The microorganisms are killed and degraded by antimicrobial
substances and are degraded by hydrolytic enzyme.
Some of the microorganisms cannot be destroyed by this
process.

The antimicrobial agents are either by

1.

Oxygen dependent bactericidal mechanisms

2.

Oxygen independent bactericidal mechanisms

3.

Nitric oxide mechanisms.

13

Oxygen dependent
NADPH

oxidase

(increase

in

oxygen

consumptions

by

phagocyte leucocytes requires presence NADPH oxidase) present in

the cell membrane of phagosome reduces oxygen to superoxide.
2O 2 NADPH Oxidase 2O - 2
This superoxide is converted into H 2 O 2 , which has bactericidal
properties.
2O 2 - + 2H + H 2 O 2
This type of bactericidal activity takes place in the presence of
enzyme MPO or independent of MPO (Myeloperoxidase)
In presence of MPO
H2O2

MPO
Cl - Br I -

HOCl + H 2 O
Hypochlorous acid

Hypochlorus acid is a potent antibacterial than H 2 O 2 .

MPO Independent
O2-

OH -

Fe-

OH -

H2O2

Bacterial activity is by the production of hydroxyl group by

Habber-Weiss reaction or in the presence of Fenton reaction.

14

Oxygen Independent
Some agents relived from the granules of phagocytic cells, do
not require oxygen for bactericidal activity. They include lysosomal
hydrolases..
Nitric Oxide Mechanism
In experimental animal, NO has shown antifungal and anti
parasites action, but role of bactericidal activity is still unknown.
Endothelial cells and macrophages produces NO.
Chemical Mediators
There are factors, which can enhance vascular permeability but
recent study shows chemical mediators not only enhance vascular
permeability but cause, fever, pain, chaemotaxis, tissue damage etc.,
They are classified as,
1.

Factors released from the cells

2.

Factors released from the plasma

Cell derived mediators

1.

Vasoactive amine

2.

Arachidonic acid metabolites

3.

Lysosomal Components

4.

Platelet activating factor

5.

Cytokines

Plasma derived mediators

15

The Kinin system

The Clotting system
The fibrinolytic system
The complement system
I.

Vasoactive amine
Two important vasoactive amines

a.

1.

Histamine

2.

5-hydroxy tryptamine

Histamines
They are found in the granules of mast cells, platelets and

basophils.
They are released by
a.

Stimuli or substance inducing acute inflammation

b.

Anaphylatoxins like fragments of complement C 3 a

and C 5 a

c.

Histamine

releasing

factor

from

neutrophils,

monocytes and platelets

Main function is vasodilation, increase in vascular permeability,
itching and pain.
b. 5 hydroxy tryptamine
It is present in tissue like chromaffin cells in GIT, spleen,
nervous tissue, mast cell etc., same actions as histamine, but
vasodilation and vascular permeability not upto histamine.

16

II.

Arachidonic acid metabolism

- Fatty acid
- 2 source (1) either by food, (2) conversion of lenoleic acid into
arachdonic acid
Arachidonic acid is converted into arachidonic acid metabolites,
by a stimuli or a mediator like C 5 . This can occur in 3 pathways via,

1.

1.

Cycloxygenase pathway

2.

Lipo-oxygenase pathway

3.

Non-enzymatic pathway

Cycloxygenase pathway
These include prostaglandin, thromboxane A2 and prostacyclin.
Prostaglandins were the name given to substances that are

isolated from seminal fluid, but now it has been isolated from many
body tissues, prostaglandin and related compounds are called
autacoids.

Activated arachidonic acid

Cycloxygenase
PG2 (Prostaglandin Endoperoxide)
Enzymatically
PGH 2 + Free oxygen radial
Transformed
Enzymatic

17

PDF 2

PGD 2 , E 2

TxA

PGI 2

- Vasodilator

- Vasodilator

- Vasoconstriction

- Bronchodilator

- Bronchoconstriction

- Bronchoconstriction - Vasodilation

- Increase in

- platelet

vascular permeability

aggrevator

- Broncho dilation
- Anti
aggregating
agent

Lipooxygenase
Activated arachnoid acid
Lipoxygenase
HPETE

5HETE (Chaemotatic agent)

LTA4

LTB4

LTC4

LTD4

LTE4

Chaemotatic

Vaso constriction

Cell adherence

Broncho constriction
Increase in vascular permeability

a. 5 HETE
It is a Chemotatic agent for neutrophils

18

b.

Leukotrienes

They are derived from the leucocytes

Non-enzymatic pathway
Arachidonic acid with out any enzymatic action leads to the
formation of metabolites of lipids that are Chaemotatic in nature
3.

Lysosomal components
Inflammatory

cells

neutrophils

and

macrophage

contains

lysosomal granules which when degraded act as a mediator for

inflammation.
Neutrophil granules: 2 types
Specific or secondary lactoferin, lysozyme, alkaline phosphate
Primary Myeloperoxidase, acid hydrolase and neutral
protease.
Acid protease act within the cell, causes destruction of bacteria
in phagolysosome.
Neutral proteases causes destruction of basement membrane,
collagenase, elastic cartilage etc.,
This destruction is kept in check by antiproteases like 1 anti
trypsin, 2 macro globulin

Granules of monocytes and tissue macrophages

They also release mediator of inflammation like acid protease,
collagenase,

elastase

etc.,

they

are

more

active

in

chronic

inflammation rather than act as a mediator in acute inflammation.

19

Platelet activating factor

They are released from IgE sensitive basophils or mast cells;
endothelium and platelets. Apart from platelet aggregation they act on
mediators in inflammation.
Increase in vascular permeability
Vasodilation in low concentration
Broncho constrictor
Chaemotaxis
Adhesion of leucocytes to endothelium
Cytokines
These are substances, which are produced from activated
leucocytes and monocytes. These substances releasenterleukin-1 and
tumor necrosis factor, which
Increases the adhesion of leucocytes to endothelium
Increases the synthesis of prostacyclin which is a
vasodilator and anti aggregator
Increases the synthesis of PAF

Nitric oxide and oxygen metabolites

-

NO originally described as vascular relaxation factor

Activated macrophages produce No during the oxidation of

arginine by enzyme NO synthetase
Vasodilation
20

 Antiplatelet activating agent

Possibly microbicidal action
Oxygen derived metabolites
Activated macrophages and neutrophils release super oxide and
toxic No products.
Endothelial cell damage, hence increase in permeability
Activation of protease and inactivation of antiproteases causing
tissue matrix damage
The actions of free radicals are co-interacted by antioxidants
present in tissue and serum, which play a protective role.
Source

Mediator

Main action

Mast cell, basophils Histamine increasing permeability

Cell

Platelets

Serotonin

increasing permeability

derived
Inflammatory
Cells

Lysosymal
enzyme, P A F,
Prostaglandin,
Leukotriens,
cytokines, NO
and oxygen

increasing permeability
tissue damage
Increasing Vasodilation,
Fever

Plasma derived mediators

These includes products that are produced by the interaction and
activation of the four interlinked system
1.

Kinin

2.

Clotting

21

3.

Fibrinolytic

4.

Complement

Hageman factor plays an important role, in the interaction of the

four systems. Activation of factor XII invivo by contact with basement
membrane or by bacterial endotoxin and invitro by kaolin or glass
leads to activation of fibrinolytic, clotting and Kinin system.
In inflammation, the factor XII is activated by those substance,
which leak through the endothelium and activate the fibrin, clotting
and kinin system. These end products activate the complementary
system that generates permeability factors. These permeability factors
in turn activate the clotting factor.
Factor XII
Contact
Factor XII A

Fibronolytic system
Plasma

Clotting System
Fibrin

Kinin System
Bradykinin

Fibrin split products

Complementary system
Permeability factor C 3 a C 5 a

22

Kinin System
Generates Bradykinin on activation with factor XII
Factor XII

Contact

Factor XII A
Prekallikrien activator

Plasma Prekallikrien

Kallikrein

Kininogen

Bradykinin

Bradykinin produces
Increased permeability
Pain
Smooth muscle contraction
Clotting system
Factor XII A initiates the cascade of clotting
Factor XII

XII A
XI A

XI A
VII A
PF 3
X

23

XA

VA
PF 3
Prothrombin

thrombin

Fibrinogen

Fibrin

Plasmin
Fibrinopeptides

The action of fibrinopeptides are

Increased vascular permeability
Anticoagulant activity
Chemotaxis for leucocytes

Fibronolytic system
Activated by plasminogen activator which consists of Kallikrein
of Kinin system endothelial cells and leukocytes
Plasminogen activator
Plasminogen

Plasmin
Fibrin split products

Plasmin actions in inflammation are,

Activator of factor XII to form Prekallikrien
Splitting of complementary system C 3 to form C 3 a, which is a
permeability factor.

24

 Produce

fibrin

split

products,

which

increase

vascular

permeability.

Complementary System
Activation of complementary system can occur either by
Classic pathway through antigen antibody complexes or
Alternate pathway via non-immunologic agents, such as
bacterial toxins, cobra venom and IgA.

Complementary system on activation yields Anaphylatoxins and

Membrane Attack Complex (MAC) Which
Release the histamine from mast cells and basophils
Increase inthe vascular permeability
C 5 a is Chemotatic agent for leucocytes
Regulation of Inflammation
Self-damaging effect caused by release of inflammatory
mediators are kept in check by the host mechanism. These include,
Acute phase protein
Acute phase protein is released in response to tissue trauma and
infection. They are 1 anti trypsin and 1 acid glycopreotein, protease
inhibitors, C-reactive protein, serum amyloid A and P component etc.,

25

They are synthesized in liver and release occurs in response to

circulatory cytokine. APP combined with systemic features of fever
and leucocytes is termed acute phase response. Deficient synthesis
leads to severe form or disease in chronic and repeated inflammatory
response.

Corticosteroids
Endogenous glucocorticoids act as anti-inflammatory agents.
They are raised in inflammation and trauma by regulating mechanism.

Free cytokine receptors

Free cytokine receptors in serum correlates directly with disease
activity.
Suppresser T-Cells
Prohibition of suppressor T cell is somewhat that inhibits
function of T and B cells.

Anti Inflammatory Chemical mediators

PGE 2 and prostacyclin have pro-inflammatory as well as antiinflammatory action.

26

Inflammatory Cells
The main cells taking part in inflammation are leucocytes,
macrophages and plasma cells.

Polymorphonuclear Neutrophils
-

Commonly called Neutrophils

Neutrophils,

basophils

and

eosinophils

are

called

granulocytes due to presence and granular in cytoplasm.

-

Granules

contain

proteases,

myeloperoxidase,

lysosymal, esterases, acid and alkaline phosphatase and

cationic proteins.
-

10-15m and actively mobile 40-75%

Their number is increased during bacterial infection

known as Neutrophilia

Arise from bone marrow

Functions
Phagocytosis:
They are first line of body defence toward infection. The step
involves adherence to endothelial cell, emigration, chemotaxis,
engulfment, degranulation, killing and degradation
Engulfment:
Of antigen-antibody complex and non-microbial material
Harmful Effect:
27

Causes destruction of basement membrane of glomeruli and

small blood vessels
Eosinophils
- Larger than neutrophils
- But lesser in number
- Similar to neutrophils in production in bone marrow and the
- Presence of granules, locomotion etc.,
- Basic major protein and eosinophil cationic protein are those, which
have bactericidal and toxic action against helminthic parasites.
- Richer in myeloperoxidase but lack lysosymal granules
- High level of steroid hormones lead to a fall or disappearance of
eosinophils from blood
- Eosinophils number is increased in some conditions like
A) Allergic condition
B) Parasite infection
C) Skin diseases
D) Certain malignant lymphoma
Basophils
- 1% in circulatory leucocytes
- It is similar to mast cells in pharmacology function.

28

- Cytoplasm contains granular and polymorphonuclear nucleus

- Granules with heparin and histamine
- They are receptors of IgE hence, degranulated when cross-linked with
antigen.
- Role in inflammation are
In immediate and delayed hyper sensitivity reaction
Release

of

histamine

by

IgE

and

sensitized

Basophils.
Lymphocytes
- Apart from blood they are found in spleen, thymus, lymph nodes, and
mucosa associated lymphoid tissue.
- Scanty cytoplasm and consist entirely of nucleus
- Besides their role in antibody formation (B-lymphocytes) and cell
mediated immunity (T-lymphocytes) they take part in inflammatory
response
In tissue dominant cells in chronic inflammation and in late
stage of acute inflammation
In blood their number is increased in chronic inflammation
Plasma Cells
- Larger than lymphocytes
- Abundant cytoplasm with eccentric nucleus which has a cart-wheel
pattern of chromatin
29

- They are derived from lymphocyte

- Not seen in peripheral blood
- Rich in RNA and globulin in cytoplasmi
- More active in antibody synthesis their number increase in
Prolonged infection with immunological response
Hypersensitivity state and
Multiple myeloma
Mono Nuclear Phagocyte System
These include 2-cell system derived from 2 sources, which have
common, morphology, function and origin.
Blood monocytes consist of 4-8% of circulating leucocytes.
Tissue macrophages
a. Macrophages in inflammation
b. Histiocytes connective tissue
c. Kupffer cells liver cells
d. Alveolar macrophages lungs
e. Macrophages serous cavity
f. Langherhans cells skin
They are not only inflammatory cells but also Scavenger
participates in the immune system.

30

cells

and

Role in Inflammation
1.

Phagocytosis & Pinocytosis

2.

Macrophages when activated with lymphokines or by nonimmunological stimuli given out biologically active substances.
i. Proteins like collagenase and elastase
ii. Plasminogen activator
iii.Some coagulation factor (factor V and thromboplastin) which
convert fibrinogen into fibrin
iv. Chaemotatic agents for other leucocytes
v. Metabolites of arachidonic acid
vi. Cytokines like Interleukin 1 and TNF

Giant Cells
When monocytes fail to remove the particular antigens, they
fuses with particular to form giant cell. The giant cells seen in
inflammation are
Foreign body giant cells
-

Contain numerous nuclei similar to macrophage

Uniform size, scattered in cytoplasm

Seen in infective tuberculosis and leprosy

Langhans giant cell

Nucleus similar to macrophage nuclei

31

Seen in tuberculosis and sarcoidosis

Nuclei arranged either in the periphery like a horseshoe or

clustered at two poles.

Touton giant cells

Multinuclear cells have vacuolated cytoplasm due to lipid
content

Tumor Giant cells

-

Larger in size

Have several nuclei, hyper chromatic

They vary in size and shape

Not formed by macrophages but from dividing nuclei of

neoplastic cell (e.g.) carcinoma of liver

Miscellaneous Cell
-

Numerous nuclei in mesoderm cell (e.g.) Aschoff cell of

rheumatic nodule, Reed stern berg cell of Hodgkins disease

Factors determining variation in inflammatory response

Acute inflammation is characterized by vascular and cellular
events with emigration of leucocytes, but not all examples show
emigration of neutrophil with acute inflammation and vice versa.

32

Typhoid fever is an acute inflammation but cellular response in

it is lymphocytes. Osteomyelitis is a chronic inflammation but cellular
response is neutrophilic.
Factors involving the organisms
1.

2.

Type of injury and infection

-

Skin reacts to herpes simplex vesicles

Skin reacts to streptococcal boils

Lung react to pneumococci lobar pneumonia

Virulence
C. Diphtheria (gravis, intermedius and mites) produce
same exotoxin but in different amount

3.

Dose
Smaller dose local lesion
Larger dose severe spreading infection

4.

Portal of entry
Vibrio cholera is not pathogenic when injected subcutaneously
but causes cholera if swallowed.

5.

Product of Organism
Some organisms produce enzymes that help in spread of

infection

33

Hyaluronidase by Cl. Welchi

Streptokinase by Streptococci

Factors involving the host

1.

General health of host

2.

Immune state of host Immuno deficiency helps in spread of

infection (e.g.) AIDS

3.

Leucopoenia

Patients

with

low W.B.C

count

with

neutropenia or agranulocytosis develops spreading infection.

4.

Site or type of tissue involved Lung has loose texture

compared to bone hence both the tissue react differently.

Type of Exudates
The appearance of escaped plasma determines the morphological
type of inflammation.
Serous: When fluid exudates resemble serum or watery (e.g.)
pleural effusion and blister formation in burn
Fibrinous
When fibrin content is high (e.g.) pneumococci and rheumatic
pericarditis
Purulent or supparative exudate
Creamy pus as seen in infection with pyogenic bacteria (e.g.)
abcess.

34

Hemorrhagic
When

vascular

damage

occur.

(E.g.)

acute

hemorrhage

phenomena in influenza
Catarrhal
Surface inflammation of the epithelium produces increased
secretion of mucous (e.g.) common cold
Cellular proliferation
1.

No typical cellular proliferation in bacterial infection except

in typhoid fever intestinal lymphoid hyperplasia

2.

Viral infection produce cellular proliferation (e.g.) chicken

pox, herpes-simplex

3.

In glomerular nephritis, proliferation of glomerular capsular

epithelium cells resulting in crescent formation.

4.

In chronic inflammation proliferation of macrophages,

fibroblasts and endothelial cells.

Necrosis
In gas gangrene there is extensive necrosis with discolored and
foul smelling tissues. In acute appendicitis there is necrosis due to
vascular destruction.
In chronic inflammation there is caseous necrosis (e.g.)
tuberculosis
Morphology of Acute inflammation

35

Inflammation of an organ is usually named by adding suffix

its, examples are appendicitis, meningitis, cholecystits.
Pseudo membrane inflammation
Inflammatory response of mucous membrane to toxin of
diphtheria & irritant gases. As a result epithelium gets denuded with
plasma exuding on to the surface, which coagulates, and together with
necrosed

epithelium

forms

false

membrane

that

gives

the

inflammation its name.

Ulcers
Local defect on the surface epithelium of an organ produced by
inflammation.
Common sites are:Stomach
Duodenum
Intestinal ulcer in typhoid fever
Bacillary and amoebic dysentery
Varicous vein in legs.
In acute stage there is infiltration by polymorphs with
vasodilatation.
In long standing there is infiltration of lymphocytes, plasma
cells & macrophages with fibroblastic proliferation & scarring.
Suppuration:
When acute bacterial infection is accompanied by intense
neutrophil infiltrate in the inflamed tissue, it results in tissue necrosis.
36

A cavity is formed which is an abces and contain purulent

exudate and the process of abcess formation is known as suppuration.
The bacterium that causes suppuration is called pyogenic bacteria.
An abcess may be discharged to the surrounding area or drained
due to tissue destruction Resolution does not occur but instead healing
by fibrous scaring occur.
Some of the examples of abcess formation
Boil or furuncle:
Which is an acute inflammation via hair follicle and dermal tissue.
Carbuncle:
Untreated diabetics & occur as located abces in dermis a soft tissue.
Cellulitis:
Diffuse inflammation of soft tissue resulting from spreading
effect of substance like Hyaluronidase by some bacteria.
Bacterial Infection of the Blood
Bacteremia
Presence of small number of bacteria in the blood which do not
multiply, they are not detected by direct microscopy.
Example: infection with salmonella typhi streptococcus viridians
Septicemia
Presence of rapidly multiplying bacteria in the blood (e.g.):
bacilli of plague, pyogenic cocci accompanied by systemic effect like

37

toxemias,

multiple

small

hemorrhages,

and

leukocytosis

&

disseminated intravascular coagulation.

Pyaemia
Presence of small thrombi in the blood, which causes their effect
at the syte where they are lodged.
1) Pyaemic absceses or
2) Septic infarcts
Pyaemic abceses
Multiple abces can occur in the lung, cerebral cortex, heart,
kidney resulting from a small emboli fragmented from a septic
thrombus.
Microscopically shows central zone of necrosis containing
numerous bacteria surrounded by a zone of suppuration and outer zone
of acute inflammatory cell.
Systemic effect of acute inflammation
Acute inflammation not only evokes local response but also
produces systemic effect too. The systemic effect includes
1) Fever
2) Leucocytosis &
3) Lymphangitis lymphadenitis
Fever
-

Due to bacteraemia

38

Mediated through release of factors like prostaglandin,

Interleukin - 1 & T.N.F

Leucocytosis
-

Usually accompanies acute inflammation

Range will be 15000- 20000 / lit

In case of bacterial infection there will be neutrophilia

In viral infection lymphocytes

In parasitic infection there will be esnophilia

Typhoid fever is an acute inflammatory condition, however it

induces leukopenia with relative lymphocytosis.

Lymphangitis - Lymphadenitis
Usually the lymphatics & lymph nodes that drain the inflamed
tissue

show

reactive

inflammatory

changes

lymphangitis & lymphadenitis.

Fate of acute inflammation
Four Outcomes
1) Resolution
2) Healing by scarring
3) Progression to suppuration
4) Progression to chronic inflammation
Resolution

39

in

the

form

of

Complete change of inflamed tissue to normal tissue. This

occurs when tissue changes are slight and cellular changes are
reversible.
Healing by Scarring
This takes place when tissue destruction in acute inflammation
is extensive so that there is no tissue regeneration but actually there is
healing by fibrosis.
Suppuration
When there is extensive tissue destruction it eventually leads to
tissue necrosis,
-

Initially there is neutrophilic infiltration

Subsequently

mixture

of

neutrophils,

necrosed

tissue,

bacteria cell debris and fibrin, comprises pus, which is

contained in a cavity to form abcess.
-

This abcess not drained get organized by fibrous tissue and

get calcified by time.

Chronic inflammation
Acute inflammation progress to chronic inflammation in those
conditions in which inflammation and healing proceeds side by side.
Definition for Chronic Inflammation
It is defined as a prolonged process in which tissue destruction
and inflammation occur at the same time.
It can occur in 3 ways

40

1.

Chronic inflammation following acute inflammation

When tissue destruction is extensive and bacteria persist in
small number at the syte of acute inflammation (e.g.)
Osteomyelitis

2.

Recurrent attack of acute inflammation

Repeated bouts of acute inflammation leads to chronicity of the
process (e.g.) repeated renal infection (UTI Infection) leading to
pyelonephritis.

3.

Chronic inflammation starting

When the infection with the organism with low pathogenicity is
chronic from the beginning (e.g.) infection with mycobacterium
tuberculosis

TYPE OF CHRONIC INFLAMMATION:

1. NON- SPECIFIC
2. SPECIFIC
1. Non-specific: when the irritant substances produce a non-specific chronic
inflammatory reaction with granulation tissue formation and healing by
fibrosis. E.g. Chronic Osteomyelitis
2. Specific: When the irritant substances produce a characteristic
histological response. E.g. TB, Syphilis etc.
A variant of this type shows chronic supparative inflammation in which
infiltration of polymorphs and abscess formation are additional features.
E.g. actinomycosis.
General features of Chronic Inflammation

41

Mononuclear cell infiltration

-

Mononuclear inflammatory cells like phagocytes and lymphoid

cells infiltrate chronic inflammatory lesions.

Macrophages comprise the most important cells in chronic

inflammation.

They may appear at the site of inflammation

Chaemotatic factors for macrophages

Local proliferation of macrophages

Longer survival of macrophages

Blood monocytes on reaching the extra vascular space transform

into tissue macrophages

Beside their action in phagocytosis, they may get activated in

response to stimuli such as cytokines and bacterial endotoxin

On

activation

macrophages

release

biologically

active

substances. These substances bring about tissue destruction,

neovascularization and fibrosis
Chronic granulomatous inflammation
Characterized by formation of granuloma (e.g.) leprosy, syphilis,
tuberculosis
Granulomatous inflammation
Granuloma derived from granule meaning circumscribed
granule like lesion oma means true tumor but here it indicates
inflammatory mass or collection of macrophages. Epithelial cell and

42

lymphoid cell are main contents of granuloma beside this they have
giant cells,as they undergo necrosis and fibrosis.
Giant Cells
Formed by fusion of epithelial cells and have 20 or more nuclei.
The nuclei may be arranged like horseshoe or clustered at two poles or
they may be present centrally (foreign body giant cells). Langherhans
cell seen in tuberculosis but foreign body giant cell seen in foreign
body tissue reaction.
Necrosis
Central caesation necrosis of tuberculosis so called because of
cheese like appearance and consistency.
Fibrosis
Occur due to proliferation of fibroblast, formation of granuloma is by,
-

Presence of poorly digestible irritants which may be organism

like mycobacterium tuberculosis

Presence of cell-mediated immunity to the irritant there by

the role of hypersensitivity in granulamatous inflammation.

Healing
-

Injury to tissue may result in cell death

Healing on the other hand is the body response in an attempt

to restore normal structure and function.
This is by

Regeneration

43

When healing takes place by proliferation of parenchyma cells

and results in complete restoration of the original tissues.

Repair
When healing takes place by proliferation of connective tissue
elements resulting in fibrosis and scarring.
At times both the process takes place simultaneously.
Most likely mediators in inflammation
a.

Vasodilation - Prostoglandins

b.

Increase in vascular permeability vaso active amine

C 3 a & C 3 5,

c.

Leukoteriens, Bradykinin
Fever Prostaglandin

d.

Pain Prostaglandin

e.

Tissue damage Neutrophil, macrophage, lysosymal enzyme

Inflammation relating to gingiva and periodontium

The gingival tissue is constantly subjected to mechanical and
bacterial aggression. The saliva; the epithelial surface and initial stage
of inflammatory response provide resistance.
Gingivitis Inflammation of gingiva
Etiology

44

Local

Systemic

1. Micro organisms in plaque

1. Nutritional deficiency

2. Calculus

2. Drug action

3. Food impaction

3. Pregnancy, diabetes and

other endocrine dysfunction

4. Faulty restoration

4. Allergy

5. Mouth breathing

5. Hereditary

6. Tooth malposition

6. Psychic phenomena

7. Chemicals or drug application

7.

Specific

granulamatous

infection
8. Neutrophil dysfunction
Clinical features of gingivitis
1.

Gingival Bleeding
-

Early sign of gingivitis

Increased

gingival

fluid

production

in

chronic

inflammation
Abnormal gingival bleeding caused by mechanical trauma, the
site of bleeding on probing has a greater area of inflamed connective
tissue cellular infiltration are predominantly lymphocytes.

Histopathology
45

Dilation and engorgement of capillaries and thinned degenerated

epithelium this causes rupture of capillaries and gingival bleeding
due to stimuli.
Color
Normal gingiva is coral pink it becomes reddish when there is
increased vascularity or decrease in keratnisation.
In acute gingivitis color change may be marginal diffused or
patch like
In chronic gingivitis it is red, reddish blue, deep blue with
increasing chronicity of inflammatory process.
Change in consistency of gingiva
Normal gingiva is firm or resilient
Acute gingivitis

chronic gingivitis

1. Diffuse puffiness and softening

1. Spongy puffiness that pit on

Pressure

2. Grayish flake like particles of debris

2. Mark softness and friability

adhering to eroded surface

3. Vesicle formation

3. Firm leathery consistency

Change in position of gingiva

Actual Position: is the level of the epithelial attachment on the tooth.
Apparent position: is the crest of the gingival margin.
The sevearity of recession is determined by the actual position
of gingival and not its apparent position.

46

Change in surface texture

Textured surface like that of an orange peel referred as stripping
in attached gingiva, loss of stripping is an early sign of gingivitis.
Change in gingival contour
Depends upon the tooth and alignment in the arch. Marginal
gingiva envelops the teeth in a collar like fashion-scalloped outline on
facial and gingival surface.
Inflammatory enlargement
1.

Acute

2.

Chronic

Acute
Sudden onset, bright red color, pain present (e.g.) gingival
abcess, periodontal abcess, pericornitis
Chronic
Persistent long lasting gingival enlargement usually painless.
Caused by exposure to plaque.
Role of inflammation in gingival disease varies in 3 ways.
1 Inflammation due to primary or due to pathologic changes.
2 Inflammation may be secondary super-imposed on systemically
caused gingival disease (e.g.) gingival hyperplasia cased by
phenytoin

47

3 Inflammation may be the precipitating factor responsible for

clinical changes in patients with systemic condition (e.g.)
pregnancy gingivitis.
Other type of gingival inflammation:

ANUG

Acute hepatic gingivo stomatitis

Allergic gingivitis

Skin disease that involve gingival tissue

Gingivitis that is initiated by bacterial plaque

Drug induced gingival enlargement

Summary
Early stages of gingival inflammation are redness, tendency to
bleed, tenderness, sponginess, slight swelling, and development of
probing depth.
Edema & inflammation extends from the interdental papillae and
marginal gingival and obliterate stippling. Hyper-plastic enlargement
is evident.
The papilla spread laterally over both surface and become
blunted.
The disease process enter deeper in to interdental tissue
involving bone and is termed periodontitis.

48

In periodontitis the interdental papilla is destroyed and the

vessels in the inflamed area become more prominent because they
dilate. Inflammation changes are accompanied by an increase blood
supply to gingiva. Inflammatory changes are so evident because
-

The Epithelium is translucent

Gingiva has a rich and have extensive blood supply.

In inflammation the permeability of the vessels is increased,

there is vascular proliferation vascular leakage. The combination of

translucent

epithelium collagen fiber

destruction and

increase

vascularity contributes to increased redness.

Vascular leakage promotes edematous change in surface texture
and contour with inflammation that may extend in to underlying tissue
of the periodontium resulting in bone loss.

49