INFLAMMATION

Overview
• For successful survival of an organism, it is imperative
that it is able to deal with injuries.
• In higher animals, response to injury is complex and
involves both local and systemic responses.
• Systemic response is both neural and humoral in
nature.
• Inflammation exemplifies local response to injury. It
consist of changes that allow different fighters of the
body to reach the site of injury.
• Both local and systemic responses continue as long as
tissue damage is taking place.
– This helps to overcome the harmful stimulus.
– It also facilitates removal of the detritus that is the product of
this conflict.
 Definition of Inflammation
 Definition 1: It is the reaction of the vascular
and supporting elements of a tissue to injury.
It results in formation of protein rich exudate,
provided the injury is not severe enough to
destroy the area.

 Definition 2: It is the response of

vascularized connective tissue to injurious
stimulus
Significance of Inflammatory
Response
Advantages:
 It destroys or limits the growth of offending
microbes.

 It isolates the injured area.

 It inactivates toxic substances that are

produced during the inflammatory response.

 It prepares the damaged area for subsequent

healing and repair.
Significance of Inflammatory
Response
Disadvantages:
 It produces pain and swelling and thus disability.
 It may result in rupture of a viscus or a large vessel.
 Excessive scar tissue can form. This produces contractures,
adhesions and keloids.
 Fistula formation can occur.
 Inflammatory detritus can itself propagate the inflammatory
response.
 An inappropriate immune response can produce several acute
and chronic diseases.
 Abscess formation can act as a space occupying lesion.
 Inflammation is responsible for diseases like atherosclerosis, MI
and neuro- degenerative disorders.
Different types of Inflammatory
Responses
 Acute Inflammation:

It is of shorter duration - measured in hours or few days.

It is characterized by presence of exudation that produces

edema.

Emigrating cells are mainly neutrophil leukocytes.

 Chronic Inflammation:

It is of longer duration- measured in days or even years.

Emigrating cells are mainly mononuclear leukocytes.

In addition features of repair are an important constituent of

chronic inflammation.
 Stimuli for Acute Inflammation
 Infection
 Immune reaction (e.g. bee sting)
 Other stimuli
 Tissue necrosis (acute myocardial
infarction)
 Trauma
 Radiation
 Burns
 Foreign bodies (e.g. glass, splinter)
Cardinal Signs of Acute
Inflammation
 Redness (rubor): occurs due to vascular
dilatation.
 Heat (calor): occurs due to hyperemia in
the affected part.
 Swelling (tumor): Due to edema and
collection of cells.
 Pain (dolor): due to release of factors like
bradykinin and PGs
 Loss of function (functio leasa)
Signs of Inflammation
Clinical appearance of Inflamed tissue
Clinical appearance of early acute
inflammation
Inflamed Pharynx
Apthous Ulcer with features of Acute
Inflammation
Aphthous Ulcer - Features of Acute
Inflammation
Pyogenic
Granuloma
Lymphangitis
showing
features of
acute
inflammation
Certain Definitions
 Exudate: It is escape of fluid, proteins and blood
cells from vascular system into interstitial tissue
or body cavities. It has high protein concentration
(SG > 1.018). Exudation occurs because of change
in vascular permeability.

 Transudate: It is escape of fluid from vascular

system into interstitial tissue or body cavities due
to increased hydrostatic pressure. Its protein
content is lower (SG < than 1.012).

 Edema: It is presence of excessive fluid in

interstitial tissues or body cavities. Nature of fluid
can be either exudate or transudate.
 Pus: It is the form of inflammatory exudate
that is rich in leukocytes and cell debris.

 Opsonins: Factors in plasma that enhance

phagocytosis.

(Sir Almorth Wright following up one of

Metchenikoff’s most suggestive biological
romances, discovered that the white blood
corpuscles or phagocytes which attack and
devour disease germs for us, do their work
only when we butter the disease germs
appetizingly for them with a natural sauce
which is named opsonin - Sir Bernard Shaw)
Purulent exudate over surface of the
brain
Inflammatory Exudate on the surface of
Colon
 Characteristic Events in Acute
Inflammation
Vascular Events:
• Changes in vascular caliber and flow.
• Increased vascular permeability and
formation of fluid exudate.
Cellular Events
• Leukocyte adhesion and transmigration
• Chemotaxis
• Leukocyte activation
• Phagocytosis
• Release of leukocyte products with resultant
tissue injury
Vascular Events in Acute
Inflammation

Initial Vasoconstriction Arteriolar dilatation

Action of
histamine &
Due to action
leukotrienes
of histamine

Fluid Exudation Increased Vascular Permeability

Due to endothelial cell

retraction/damage
Vascular
Dilatation
 Ultra
filtration
of
Fluid
Advantage
Increased fluid

Dilutes toxins

FLUID CONTENT
1. Globulins: Protective antibodies
2. Fibrin deposition: Helps to limit spread of bacteria
3. Various factors promoting subsequent healing
 Cellular Events in
Acute Inflammation
Margination and rolling of
neutrophils
Adhesion and pavementing of
neutrophils
Neutrophil
emigration/diapedesis
Chemotaxis
Leukocyte activation
Phagocytosis
Release of leukocyte products
and leukocyte induced tissue
injury.
 Leukocyte
Rolling
Exudation of fluid

Increased Viscosity

Loss of Axial Stream

Rolling of neutrophils

Selectins on
endothelial cells
recognize CHO
on neutrophils
 Margination and Pavementing

1. Integrin adhesion molecules are present on endothelial cells and

neutrophils.
2. Activation of these molecules cause firm adherence of neutrophils to
endothelial cells
 Leukocyte
trans-migration

Leukocytes dissolve
the basement membrane
and enter interstitial tissue

xudate accumulates
n the interstitial tissue.

xudate
Dilutes toxins
Provides opsonins to
aid phagocytosis
 Diagrammatic representation of Chemotaxis

• Neutrophils follow chemical gradients that lead to the infection site.

• Chemotactic mediators like C5a, LTB4, bacterial products and IL8

bind to neutrophils.

• Binding increases neutrophil motility.

Phagocytosis and Killing
 Process of phagocytosis involves: recognition, engulfment,
killing and degradation of the offending agent.

 Recognition is carried out with the help of mannose and

scavenger receptors present on the surface of phagocytes.

 Phagocytosis is enhanced when microbes are opsonized.

 Microbe is taken up in the phagosome that fuses with

lysosome to form phagolysosome.

 Killing of microbes involves generation of ROS. In addition

H20:MPO system generates HOCL. These are very potent
microbicidal substances.
 Phagocytosis, Ingestion. Bacterial
Killing
It is a multistep process consisting of
1. Opsonization
2. Ingestion
3. Killing

• Defect in opsonization: Bruton’s agammaglobulinemia.

• Defect in ingestion: Chediak Higashi syndrome
• Defect in bacterial killing: Chronic granulomatous disease.
Events of Acute Inflammation – Some Salient
Features
 Pavementing is induced due to increased expression of adhesion
molecules, a process enhanced by C5a, LKB4 and TNF.
 Adhesion molecules belong to the family of selectins, integrins,
immunoglobulin superfamily and mucin like glycoproteins.
 Diapedesis is coordinated by chemokines. Chemotaxis is regulated by
chemokines and other factors like bacterial products, complement
components and leukotrienes.
 Genetic disorders of adhesion molecules can increase susceptibility to
bacterial infections.
 On reaching the site of injury, leukocytes are activated, a process
induced by chemotactic factors, Ag:Ab complexes and product of
bacteria. Activated leukocytes produce AA metabolites, release
lysosomal enzymes and secrete various cytokines.
Transmigratio
n
of
Lymphocyte
 Lobar
Pneumonia
Appendix: Congestion and emigration of
neutrophils
Emigrated neutrophils in alveoli of
Lung
Neutrophils collecting in between cardiac
muscle fibers
Gram stain to
show
phagocytosis
of bacteria by
neutrophils
Cell infiltrate of acute Inflammation
Cell infiltrate of acute
inflammation