acute inflammation

INDIAN
DENTAL
ACADEMY
Leader in
continuing
Dental
Education
www.indiandentalacademy.com

REFERENCES
• Robbins,Kumar,Abbas,Mitchell,Fausto. Textbook of
Basic Pathology ,8th Edition.
• Harshmohan.Textbook of Essential pathology, 5th
Edition.
•Walter and Isreal. General pathology 6th edition.

Learning objectives:
At the end of the seminar learner should
be able to:
1. Define inflammation.
2. Enumerate cardinal signs, causes of
inflammation.
3. Describe events in acute inflammation .
4. Describe inflammatory mediators.
5. Describe outcomes, morphological
patterns of inflammation.
6. Describe the clinical importance of
inflammation.

History:
 Signs of inflammation were described in an
Egyptian papyrus, (3000 B.C.)
 Celsus, a roman writer, in 1st century A.D., first
listed four signs of inflammation
 Rubor - Redness
Tumor - Swelling
Calor - Heat
Dolor - Pain
 Rudolf virchow (1858), added fifth sign,
Loss of function (functio laesa)

SIGNS OF INFLAMMATION

Definitions :
“The local response of living mammalian
tissue to injury due to any agent”.
“Inflammation is a protective response
intended to eliminate the initial cause of cell
injury as well as the necrotic cells and
tissues resulting from the original insult.”

CAUSES
1. Physical
agents
2. Chemical
agents
3. Infective
agents
4. Immunological
agents
heat, cold, radiation and
mechanical trauma.
organic and inorganic
poisons.
bacteria, viruses and their toxins.
cell-mediated and antigen-
antibody reactions.

Inflammation
Acute Chronic
Acute versus chronic inflammation are distinguished
by the duration and the type of infiltrating inflammatory cells

“It is a rapid response to injury or
microbes and other foreign substances
that is designed to deliver leucocytes
and plasma proteins to sites of injury.”

• The changes in acute inflammation can be
described under the following headings-
1 ) Vascular changes
- Changes in vascular caliber and flow.
- Increased vascular permeability.
2) Cellular events
- Exudation of leucocytes
- Phagocytosis

VASCULAR
CHANGES

Vascular events
Alteration in the microvasculature is
the earliest response to tissue injury,
they are:
 Hemodynamic changes
 Increased vascular permeability

Haemodynamic changes
The earliest feature of inflammatory
response results from change in
vascular flow and caliber of small blood
vessel in injured tissue.

1) Transient vasoconstriction of
arterioles:
-Immediate vascular response
irrespective of the type of injury.
-Vasoconstriction in mild to moderate
injury: 3-5 seconds
-In severe injury : lasts upto 5 minutes

2) Persistent progressive
vasodilatation :
-Mainly involves arterioles, venules .
- Changes are seen within half an
hour.
- Vasodilatation results in increased
blood volume in the area responsible
for heat and redness.

Vascular dilatation

3) Elevation of local hydrostatic pressure
: Results in transudation of fluid into
extracellular space causing swelling at
the site of inflammation.

4)Slowing or stasis of the
microcirculation
 Caused by prolonged vasodilatation and
increased permeability of
microvasculature
 Increased concentration of red cells
 Increased blood viscosity

5) leukocyte margination ( peripheral
orientation)
 Leukocytes mainly neutrophils stick to the
vascular endothelium
 moves and migrates through endothelial
gaps into extracellular space called as
emigration.

Triple response: It demonstrates
features of haemodynamic changes in inflammation

The Triple Response
 Red line, Flare& Wheal (Lewis, 1927)
 Take a blunt instrument and draw a line on
your forearm.
• Red line appears due to vasodilatation of
capillaries and venules in response to injury.
• Flare is red irregular zone or flush
surrounding the red line, that develops due to
arteriolar dilation.
• Wheal a zone of edema due to fluid
exudation.

ALTERED VASCULAR
PERMEABILITY

Vascular changes & fluid leakage during acute inflammation
lead to Edema in a process called Exudation
Transudate
•Result of hydrostatic
imbalance
•Low protein content
•Specific gravity < 1.015
Exudate
•Result of inflammation
Vascular permeability
•High protein content
•specific gravity >1.020

STARLING’S HYPOTHESIS
 Fluid balance is maintained by 2 opposing sets of
forces:
1) Intravascular hydrostatic pressure & interstitial
osmotic pressure – Causes outward movement of
fluid from circulation.
2) Intravascular osmotic pressure & interstitial
hydrostatic pressure – Causes inward movement
of fluid.

Increased vascular permeability is due to :-
• Reduced osmotic pressure in the vasculature
• Increased osmotic pressure in the interstitium

Mechanism of
increased vascular
permeability:

• Short – lived.
(15-30 min.)
• Reversible
process.
• For e.g. Mild
thermal injury

•Endothelial cell contraction occurs rapidly after
binding of mediators to specific receptors , is
called the immediate transient response.
•A slower and more prolonged contraction of
endothelial cells, resulting from changes in the
cytoskeleton, may be induced by cytokines
such as tumor necrosis factor (TNF) and
interleukin-1 (IL-1).
•This reaction may take 4 to 6 hours to develop
after the initial trigger and persist for 24 hours
or more.

• It is usually seen
after severe
injuries
(burns and some
infections).

 In most cases leakage begins immediately after
the injury and persists for several hours (or days)
therefore, this reaction is known as the immediate
sustained response.
 Venules, capillaries, and arterioles can all be
affected, depending on the site of the injury.
 Direct injury to endothelial cells may also induce
a delayed prolonged leakage that begins after a
delay of 2 to 12 hours, lasts for several hours or
even days, and involves venules and capillaries.

• Accumulated
leucocytes release
toxic oxygen
species &
proteolytic
enzymes.

CELLULAR
EVENTS
-The cellular phase of inflammation consists of 2
processes:
1) Exudation of leucocytes.
2) Phagocytosis.

The sequence of extravasation of Leukocytes from
blood to tissues:
Margination and pavementing
Adhesion and Rolling
Emigration and Diapedesis
Chemotaxis

Exudation of leukocytes
 Changes in the formed elements of blood
 Margination:
Due of stasis of blood flow, leukocytes
assumes a more peripheral position along the
endothelial surface because of loss of plasma
by exudation and it is called as margination.
Pavementing:
The neutrophils rests and adheres to the
endothelium resembling pebbles and it is
known as pavementing.

Margination & pavementing

• Rolling and adhesion:
Pavemented neutrophils slowly rolls over the
endothelial cell lining the vessel wall this is
followed by firm adhesion.
4 type of distinct adhesion molecule:
 Selectins
 Addresins
 Integrins
 Immunoglobulin super family adhesion
molecule

Emigration
 After adhesion, neutrophils throw out their
cytoplasmic pseudopods.
It gets lodged between endothelial cells and
basement membrane.
Damages basement membrame with
secreted collagenases.
Escapes out into extravascular space.

Leukocyte adherence

CHEMOTAXIS
 The Chemotactic factors mediate
transmigration of leukocytes to reach
interstitial tissue.
 The factors are:
 Leukotriene B4
 Platelet factor 4
 Complement system
 Cytokines
 Soluble Bacterial products
 MCP-1
 Chemotactic factor for CD4 +T cells & eosinophils.

The concept of chemotaxis is well
illustrated by Boyden’s chamber
experiment.

Phagocytosis :
“Phagocytosis is defined as the process of engulfment of
solid particulate material by the cells(cell-eating)”.
Steps in phagocytosis:
1. Attachment stage
2. Engulfment stage
3. Secretion (Degranulation stage)
4. Killing/ Degradation

Stages in phagocytosis:
 1) Attachment or opsonisation:
 In order to establish a bond between
microorganism and phagocytic cell
,the microorganism gets coated with
opsonins.
 And their corresponding receptor is
present on the phagocyte.

The two main opsonins present in the serum
and their corresponding receptor on the
surface of phagocytic cell are:
1) IgG opsonin : Its receptor on Fc fragment of
immunoglobulin on surface of phagocytic cell.
2)C3b opsonin : Is a fragment of complement
and corresponding receptor for C3b on the
surface of phagocytic cells.

2) ENGULFMENT STAGE:
 The opsonised particle is engulfed by
formation of cytoplasmic pseudopods
around the particle, enveloping it in
phagocytic vacuole.
 The lysosome of the cell fuses with the
phagocytic vacuole and forms
phagolysosome.

3) DEGRANULATION:
 PMNs discharge granules into
phagosomes and extracellular
environment.
 Primary granules (azurophilic
granules) fused with phagosomes.
 Secondary granules are discharged.

4) KILLING OR DEGRADATION
STAGE:
 The microorganism after being killed
by anti bacterial substance are
degraded by hydrolytic enzymes.
 The antimicrobial agent acts by the
following mechanism :
 1) Oxygen dependent bacterial mechanism.
 2) Oxygen independent bacterial
mechanism.
 3) Nitric oxide mechanism.

KILLING OF MICRO-ORGANISMS

Stages in phagocytosis

Stages of phagocytosis of a foreign
particle

TO BE CONTINUE……….

Presented by:
Sadaf Alvi
Guided by:
Dr. Minal Chaudhary
Dr. Madhuri Gawande
Dr.Swati patil
Dr. Alka Hande

Learning objectives:
At the end of the seminar learner should
be able to:
1. Describe inflammatory mediators.
2. Describe outcomes, morphological
patterns of inflammation.
3. Describe the clinical importance of
inflammation.

CHEMICAL MEDIATORS OF INFLAMMATION

Cell-derived mediators
CELL-
DERIVED
Mast cells,
basophils,
platelets
Platelets
Inflammatory cells
Histamine
Serotonin
•PGs
•Leukotriens
•PAF
•Cytokines
•Nitric oxide &
o2 metabolite
Permeability &
vasodilatation
Permeability &
vasodilatation
Vasodilatation
.fever, pain
Permeability,
chemotaxis,
,leukocytic
adhesion
Fever , pain
Tissue damage

CELL-DERIVED
MEDIATORS

1. VASOACTIVE AMINES:
Two important pharmacologically active amines that
have role in the early inflammatory response , they are
so named as they have important action on blood
vessels .
They are:
A.HISTAMINE.
B.SEROTONIN (5- HYDROXYTRYPTAMINE).

Histamine:
 It is stored in the granules of mast cells, basophils and
platelets.
 Various factors responsible for the release of it :
 Stimuli or substances inducing acute inflammation e.g. heat,
cold, irradiation, trauma, irritant chemicals.
 Anaphylatoxins like fragments of complement C3a , and C5a,
 Histamine-releasing ptoteins from leukocytes.
 Neuropeptides such as substance P.
 Interleukins IL-1 IL-8.
It causes:-
• Vasodilatation of arterioles.
 Increased vascular permeability of venules , itching and pain.

Serotonin (5-Hydroxytryptamine)
 It is present in tissues like chromaffin cells of
GIT, spleen, nervous tissue, mast cells and
platelets.
.
 Actions :-
 increased vascular permeability
 vasodilatation .

Arachidonic acid metabolites
(eicosanoids )
 Arachidonic acid is a 20 carbon Polyunsaturated fatty
acid derived from dietary sources or by conversion from
the essential fatty acid linoleic acid.
• It is present in esterified form as a component of cell
membrane phospholipids.
• It is released from membrane phospholipids through the
action of cellular phospholipases.

3. LYSOSOMAL COMPONENTS
 Neutrophils and monocytes contain lysosomal granules, which
when released, may contribute to the inflammatory response.
These are as under:
1. Granules of neutrophils Specific/ Secondary.
Azurophil/ Primary.
2. Granules of monocytes and tissue macrophages & eosinophils.

• Large azurophil ( primary) granules contains
myeloperoxidase, bactericidal factors ( lysozymes,
defensins), acid hydrolases & variety of neutral
proteases.
•Different granule enzyme serves different functions acid
proteases act within the cell to cause destruction of
bacteria and neutral proteases attack on extra cellular
components.
• Smaller specific ( secondary) granules contains
lysozyme, collagenase, gelatinase, lactoferrin,
plasminogen activator, histamine & alkaline
phosphatase.
a. Granules of neutrophills:

b. Granules of monocytes and
tissue macrophages:
• Releases mediators of inflammation
like acid proteases,
collagenase and plasminogen
activator.
• More active in chronic inflammation.

Eosinophil granule proteins
Following activation by an immune stimulus, eosinophils
degranulate to release an array of cytotoxic granules
that are capable of inducing tissue damage and
dysfunction. These include:
•Major basic protien (MBP)
•Eosinophil cationic protein (ECP)
•Eosinophil peroxidase (EPO)
•Eosinophil-derived neurotoxin (EDN)
c.

4. Platelet-Activating Factor
Generated from membrane phospholipids of neutrophils,
monocytes, basophils, mast cells, endothelium and
platelets.
 Actions:
 vasoconstriction .
 Bronchoconstriction.
 Increased vascular permeability.
 Enhanced leukocyte adhesion.
 Chemotaxis and Degranulation.

5. CYTOKINES
• Cytokines are polypeptide substances produced by
activated lymphocytes and activated monocytes.
• TNF and IL-1, IL-6 are major cytokines that mediate
inflammation .
• Action in inflammation:
• 1) Local effects:
• Endothelium
• Leukocytes
• Fibroblasts
• 2)Systemic effects

 Chemokines are proteins that act primarily as
chemoattractants to specific types of leukocytes.
They are classified into four major groups :-
 C-X-C Chemokine: Act primarily on neutrophils.
 C-C Chemokine : chemotactic for all leukocytes except
neutrophils.
 C Chemokine: specific for leukocytes.
 CX3C Chemokine: Act on monocyte and T-cells.

6. NITRIC
OXIDE
 Nitric oxide (NO) is described as vascular
relaxation factor produced by endothelial
cells, macrophages and neurons in the
brain.
 Various functions of NO :-
 Vasodilatation.
 Anti-platelet activating agent.
 Microbicidal action.

7. OXYGEN DERIVED FREE RADICAL
 They are released extracellularly from neutrophils and
macrophages after exposure to microbes and include
superoxide oxygen (0‘2), H202, OH' .
 These oxygen-derived free radicals have the following
action in inflammation:
 Endothelial cell damage and thereby increased vascular
permeability.
 Activation of protease and inactivation of antiproteases
causing tissue matrix damage.
 Damage to other cells like RBC.

PLASMA-DERIVED
MEDIATORS

Plasma derived mediators
PLASMA-
DERIVED
FIBRINOLYTIC
SYSTEM
KININ SYSTEM
COMPLEMENT
SYSTEM
Fibrin split
products
Kinin/
Bradykinin
Anaphylotoxins
C3a, C4a, C5a
permeability
Permeability, pain
Permeability
,chemotaxis

A. Kinin system
◦ The kinins are vasoactive peptides derived
from plasma protein (kininogens) by the
action of specific proteases called Kallikreins.
◦ Bradykinin is the most important Kinin .

ACTIVATION OF KININ
SYSTEM
ACTIVATION OF KININ
SYSTEM

Functions of Bradykinin:
- Increases vascular permeability.
- Causes contraction of smooth muscle.
- Vasodilatation.
- Pain

• This system is activated by plasminogen
activator.
• The sources of which include kallikrein of the
kinin system, endothelial cells and leucocytes.
• Plasminogen activator acts on plasminogen
present as component of plasma proteins to form
plasmin.
• Further breakdown of fibrin by plasmin forms
fibrinopeptides or fibrin split products .
B.FIBRINOLYTIC SYSTEM

Fibrinolytic system

The actions of plasmin in inflammation
are:
•Splits off complement C3 to form C3a which is
a permeability factor.
• fibrin split products which increase vascular
permeability and are chemotactic to leucocytes.

C. COMPLEMENT SYSTEM
 It is a cascade system of enzymatic
proteins.
 function in both innate and adaptive
immunity.
 consists of more than 20 proteins.
 complement proteins are present in
inactive forms in the plasma .
 many of them are activated to become
proteolytic enzymes that degrade other
complement proteins. www.indiandentalacademy.com

 The critical step in complement activation
is proteolyis of C3.
 Cleavage of C3 occurs by one of the three
pathways:
1. Classical pathway
2. Alternative pathway
3. Lectin pathway

The activation and functions of the complement system.

The biologic functions of complement
system fall into 3 general categories
1) Inflammation – C5a,C3a and C4a(lesser
extent)
2) Phagocytosis-C3b acts as opsonins and
promote phagocytosis.
3) Cell lysis - deposition of MAC(membrane
attack complex)makes cells permeable to water
and ions results in cell death.

Vasodilatation Prostaglandins
Nitric oxide
Histamine
Serotonin,
Increased vascular permeability Vasoactive amines
C3a and C5a
Bradykinin
Leukotrienes
PAF
Substance P
Chemotaxis C5a
Leukotriene B4
Chemokines
Fever IL-1, TNF
Prostaglandins
Pain Prostaglandins
Bradykinin, substance p
Tissue damage Neutrophil and macrophage lysosomal
enzymes
Oxygen metabolites
Nitric oxide
Role of Mediators in Different Reactions of Inflammation

Outcomes of acute Inflammation
 Complete resolution.
 Healing by connective tissue
replacement (fibrosis).
 Progression to chronic inflammation.

Outcomes of Acute Inflammationwww.indiandentalacademy.com

MORPHOLOGIC PATTERNS OF
INFLAMMATION
1. Serous inflammation.
2. Fibrinous inflammation
3. Suppurative or Purulent inflammation
(Abscess formation)
4. Ulcers

Serous inflammation

Fibrinous inflammation

Purulent inflammation

ULCERS

APPLIED
ASPECTS

SYSTEMIC EFFECTS OF ACUTE
INFLAMMATION
 Fever
- Occurs due to bacteraemia.
- In response to infection various chemical
mediators releases like prostaglandins,
interleukin-1, TNF are released.
•Leucocytosis
Neutrophilia points to bacterialinfection.
Lymphocytosis points to viral infection.
Eosinophilia points to allergy or parasitic
infection.

 Lymphangitis- Lymphadenitis:
• 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.

Benign (reactive) lymphadenopathy
There are three distinct patterns of benign
lymphadenopathy:
•Follicular hyperplasia - Seen in infections,
autoimmune disorders.
•Paracortical hyperplasia - Seen in viral
infections, skin diseases.
•Sinus histiocytosis - Seen in inflammatory lesions
and malignancies.

Shock:
• Occur in severe cases.
• Massive release of cytokine TNF- alpha in
response to severe tissue injury or infection
results in profuse systemic vasodilatation,
increased vascular permeability and intravascular
volume loss.
•The net effect of these changes is hypotension
and shock.

CONCLUSION:
 The survival of all organism requires that they should
eliminate foreign invaders such as, infectious
pathogens and damaged tissues.
 These functions are mediated by a complex host
response called inflammation.
 Inflammation accomplishes its protective mission by,
destroying or otherwise neutralizing harmful agents.
 The body attempts to heal the damage with some
changes by the process of repair.
 The repair begins almost as soon as the inflammatory
changes have started and involves several processes,
including cell proliferation and differentiation.

THANK YOU
THANK YOU

acute inflammation

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