ACUTE INFLAMMATION ,vascular ,cellular ,events ,chemical ,mediators ,types

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PATHOLOGY OF
ACUTE INFLAMMATIONINFLAMMATION
Dr. Kafil Akhtar
Associate Professor, Dept. of Pathology
J N Medical College, AMU., Aligarh

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INFLAMMATIONINFLAMMATION

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INTRODUCTION:
“Inflame” – to set fire.
Inflammation is the “Dynamic response of
vascularised tissue to injury.”
Host response to get rid of damaged or necrotic
tissues and foreign invaders.
Is a protective response.
Serves to bring defense and healing
mechanisms to the site of injury.

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ACUTE INFLAMMATION
 It is a complex reaction to injurious agents such as
microbes and damaged, usually necrotic cells, that
consists of vascular responses, migration and activation
of leukocytes and systemic reactions.
 The unique feature of the inflammatory process is the
reaction of blood vessels, leading to the
accumulation of fluid and leukocytes in extravascular
tissues.
 It is divided into 2 patterns-
1) Acute
2) Chronic

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ACUTE INFLAMMATION
 Rapid in onset (seconds or minutes)
 Is of relatively short duration, lasting for minutes, several
hours or a few days
It has 3 major components-
alterations in vascular caliber that lead to an increase in
blood flow
structural changes in the microvasculature that permit
plasma proteins and leukocytes to leave the circulation
emigration of the leukocytes from the microcirculation,
their accumulation in the focus of injury, and their
activation to eliminate the offending agent

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STIMULI FOR ACUTE INFLAMMATION
 Infections :bacterial, viral, parasitic & microbial toxins
 Trauma (blunt and penetrating)
 Physical & chemical agents (thermal injury, irradiation,
environmental chemicals)
 Foreign bodies (splinters, dirt, sutures)
 Immune reactions (also called hypersensitivity rxn)

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LEWIS TRIPLE RESPONSE:
FLUSHFLUSH:: capillary dilatation
FLAREFLARE:: arteriolar dilatation
WHEALWHEAL:: Exudation, Edema

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CARDINAL SIGNS OF INFLAMMATION
Classical 5 Signs: Celsius 1st c. B.C. &Virchow 19th c. A.D.
RUBORRUBOR :: Redness – Hyperemia
CALORCALOR :: Warmth/Heat – Hyperemia
DOLORDOLOR :: Pain – Nerve, Chemical Mediators
TUMORTUMOR:: Swelling – Exudation
LOSSLOSS OFOF FUNCTIONFUNCTION: Functio laesa: Functio laesa

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Heat Redness Swelling Pain Loss of Function
THE 5 CARDINAL SIGNS OF

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INFLAMMATION - MECHANISM
1. Vasodilatation
2. Exudation - Edema
3. Emigration of Cells
4. Chemotaxis
5. Phagocytosis

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ACUTE INFLAMMATIONACUTE INFLAMMATION
Physiological ResponsesPhysiological Responses SymptomsSymptoms
Release of soluble mediators
Vasodilatation
Increased blood flow
Extravasation of fluid (permeability)
Cellular influx (chemotaxis)
Heat (calor)
Redness (rubor)
Swelling (tumor)
Pain (dolor)

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ACUTE INFLAMMATIONACUTE INFLAMMATION
Physiological ResponsesPhysiological Responses SymptomsSymptoms
Release of soluble mediatorsRelease of soluble mediators
VasodilationVasodilation
Increased blood flowIncreased blood flow
Extravasation of fluid (permeability)Extravasation of fluid (permeability)
Cellular influx (chemotaxis)Cellular influx (chemotaxis)
Heat (calor)Heat (calor)
Redness (rubor)Redness (rubor)
Swelling (tumor)Swelling (tumor)
Pain (dolor)Pain (dolor)

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ACUTE INFLAMMATIONACUTE INFLAMMATION
Physiological ResponsesPhysiological Responses SymptomsSymptoms
Release of soluble mediatorsRelease of soluble mediators
VasodilatationVasodilatation
Increased blood flowIncreased blood flow
Extravasation of fluid (permeability)Extravasation of fluid (permeability)
Cellular influx (chemotaxis)Cellular influx (chemotaxis)
Heat (calor)Heat (calor)
Redness (rubor)Redness (rubor)
Swelling (tumor)Swelling (tumor)
Pain (dolor)Pain (dolor)

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ACUTE INFLAMMATIONACUTE INFLAMMATION
Physiological ResponsesPhysiological Responses SymptomsSymptoms
Release of soluble chemical mediatorsRelease of soluble chemical mediators
VasodilatationVasodilatation
Increased blood flowIncreased blood flow
Extravasation of fluid (permeability)Extravasation of fluid (permeability)
Cellular influx (chemotaxis)Cellular influx (chemotaxis)
Heat (calor)Heat (calor)
Redness (rubor)Redness (rubor)
Swelling (tumor)Swelling (tumor)
Pain (dolor)Pain (dolor)

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RED, WARM & SWOLLEN (FLARE, FLUSH & WHEAL )
CALOR, RUBOR, DOLOR, TUMOR, LOSS OF FUNCTION.

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SURGICAL WOUND INFLAMMATION:
RED, WARM & SWOLLEN (FLARE, FLUSH & WHEAL )
CALOR, RUBOR, DOLOR, TUMOR, LOSS OF FUNCTION.

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Mouth Aphthus ulcer

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ACUTE ENTERITIS:
Red, Warm & Swollen (Flare, Flush & Wheal )
Calor, Rubor, Dolor, Tumor, Loss of function.

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VASCULAR EVENTS

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VASCULAR CHANGES
VASODILATATION
 Increased permeability of vessels due to widened
intercellular junctions and contraction of
endothelial cells (Histamine, VEGF, Bradykinin)

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HAEMODYNAMIC CHANGES
Transient vasoconstriction
Persistent progressive vasodilatation
Elevation in local hydrostatic pressure resulting in
transudation of fluid into the extracellular space
Slowing or stasis
Leukocytic margination

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Vasodilation
Brief arteriolar vasoconstriction followed by
vasodilation
Accounts for warmth and redness
Opens microvascular beds
Increased intravascular pressure causes an
early transudate (protein-poor filtrate of plasma)
into interstitium.

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Vascular leakage
Vascular permeability (leakiness) commences
Transudate gives way to exudate (protein-rich)
Increases interstitial osmotic pressure
contributing to edema (water and ions)

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MECHANISM OF INFLAMMATION

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VASCULAR CHANGES

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EXUDATION

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LEUKOCYTE CELLULAR
EVENTS

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CELLULAR EVENTS
Leukocytes Margination → Adhesion
(Pavementing) → Rolling → Emigration
Emigration of:
 Neutrophils (1-2 Days)
 Monocytes (2-3 Days)
Chemotaxis
 Endogenous Signaling Molecules - Lymphokines
 Exogenous - Toxins
Phagocytosis - Lysosomal Enzymes, Free Radicals,
Oxidative Burst

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NEUTROPHIL MARGINATION

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EMIGRATION OF LEUCOCYTES
Diapedesis 

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CHEMOTAXIS
 Migration of leukocytes towards site of
inflammation.
 Stimuli for movement– Chemo-attractantsChemo-attractants.
 Most commonly exogenous substances
( bacterial proteins)

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Chemotaxis
The chemotactic factor mediated transmigration of
leukocytes after crossing several barriers to reach the
interstitial tissues is called chemotaxis
The agents acting as potent chemotactic substances for
different leukocytes called chemokines are:
-Leukotriene B4 (LTB4)
-Platelet factor 4 (PF4)
-Components of complement system (C3, C5)
-Cytokines (IL-1,IL-5,IL-6)
-Soluble bacterial products (formylated peptides)
-Monocyte chemo-attractant protein (MCP-1)

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PHAGOCYTOSIS
It is the process of engulfment of solid
particulate material by the cells
There are 2 types of phagocytic cells-
-polymorphonuclear neutrophils called as
microphages
-circulating monocytes and fixed tissue
mononuclear phagocytes called as macrophages
It involves the following steps-

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PHAGOCYTOSISPHAGOCYTOSIS
Recognition and attachment
mannose and scavenger
receptors on WBC’s
Engulfment– formation of
phagocytic vacuole:
Pseudopod formation due to
Actin polymerization
Killing and degradation
PHAGOCYTOSISPHAGOCYTOSIS

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PHAGOCYTOSIS

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 Recognition and attachment /Opsonization
stage
-Ig G opsonin
-C3b opsonin

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OPSONIZATION
MAKING IT TASTY AND ATTRACTIVE
• PARTICLE– microbes
or bacterial products
or toxins
Opsonins: IgG antibody, protein
C3, mannose binding lectin,
fibronectin,fibrinogen and C-
reactive protein

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ENGULFMENT

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Killing and Degradation
Oxygen Dependent Systems: formation of
reactive oxygen species
NADPH oxidase enzyme complex
Hydrogen Peroxide—MPO—Halide system
Most potent bactericidal system of neutrophils
Polymorphs after phagocytosis undergo
apoptotic cell death

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Chemical mediators
Plasma-derived:
Complement,
 Kinins,
coagulation factors
Cell-derived:
 Mast cell- histamine
 Prostaglandins

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Specific mediators
Vasoactive amines
Histamine:
Causes vasodilatation and venular endothelial
cell contraction, Junctional widening
 Released by mast cells, basophils, platelets in
response to injury (trauma, heat), immune
reactions (IgE-mast cell)

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Specific mediators
Serotonin:
 Vasodilatory effects similar to those of histamine;
 Platelet dense - body granules;
 Release triggered by platelet aggregation

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Arachidonic acid metabolites
(eicosanoids)
Prostaglandins and leukotrienes are derived from
arachidonic acid metabolism through:
Cyclo-oxygenase and
lipoxygenase pathway

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


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Pathway of Arachidonic acid metabolism
Cyclooxygenase pathway produces:
Thromboxane: Aggregates platelets & causes
vasoconstriction
Prostacycline: Inhibit platelets aggregation and
dilates blood vessels.
Prostaglandin: Increases vasodilation and
increases vascular permeability.

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Lipoxygenase pathway produces
 Leukotrienes:
 Causes vasoconstriction and increases
vascular permeability.
 Stimulates leukocytes adhesion to the
endothelium.
are chemotaxins

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Plasma derived: Plasma proteases
Clotting factors
Complement factors
Kinins

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Kinin system
Leads to formation of bradykinin from
cleavage of precursor (HMWK)
Vascular permeability
Arteriolar dilatation
Non-vascular smooth muscle contraction (e.g.,
bronchial smooth muscle)
Causes pain

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Complement system
Components C1-C9 present in inactive form
Activated via classic (C1) or alternative (C3)
pathways to generate MAC (C5 – C9) that
punch holes in microbe membranes
In acute inflammation
Vasodilatation, vascular permeability, mast
cell degranulation: C3a, C5a
Leukocyte chemotaxis :C5a
As an opsonin, increases phagocytosis: C3b

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Specific Mediators
 PAF (platelet activating factor:
Derived also from cell membrane phospholipid
 causes vasodilatation,
 increased vascular permeability,
 increases leukocyte adhesion

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Cytokines
Polypeptide products of many cell types but mainly
lymphocytes and macrophages that act on same cell
autocrine, as a message to other cells paracrine
effect or systemically endocrine effect .
Increase endothelial cell adhesion molecule
expression and activation and aggregation of PMNs.
IL-1, TNF-α and -β, IFN-γ are especially important
in inflammation.

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Specific mediators
Nitric Oxide
short-acting soluble free-radical gas.
Produced by endothelial cells, macrophages,
causes:
Vascular smooth muscle relaxation and
vasodilatation
Kills microbes in activated macrophages

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Specific mediators
Lysosomal components
Leak from PMNs and macrophages after
demise, attempts at phagocytosis.
Acid proteases (only active within lysosomes).
Neutral proteases such as elastase and
collagenase are destructive in ECM.

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Increased vascular permeability:
 Histamine ,
 Prostaglandin,
 Leukotrienes
 Serotonin,
 Bradykinin,
 PAF (Platelet Activating Factor)
 NO (Nitric Oxide)

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Inflammation-59FACTORS DETERMINING VARIATION IN
INFLAMMATORY RESPONSE
1) Factors involving the organisms
-type of injury
-virulence
-dose
2) Factors involving the host
-general health of host
-immune state of host
-leukopenia
-local host factors

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MORPHOLOGY OF ACUTE INFLAMMATION
PSEUDOMEMBRANOUS INFLAMMATION
-it is inflammatory response of mucous surface (oral,
bowel, respiratory) to toxins of diphtheria or irritant
gases.
ULCER
-it is local defect on the surface of an organ produced by
inflammation
-common sites are stomach, duodenum, typhoid,
intestinal tuberculosis, bacillary and amoebic dysentery

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SUPPURATION (ABSCESS FORMATION)
- contains purulent exudate or pus and the process
of abscess formation is known as suppuration -boil,
carbuncle
CELLULITIS
-it is a diffuse inflammation of soft tissues resulting
from spreading effects of substances like
hyaluronidase released by some bacteria

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BACTERIAL INFECTION OF THE BLOOD
-bacteraemia
-septicaemia
-pyaemia

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SYSTEMIC EFFECTS OF ACUTE
INFLAMMATION
1. FEVER
2. LEUKOCYTOSIS
3. LYMPHANGITIS-LYMPHADENITIS
4. SHOCK

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FATE OF ACUTE INFLAMMATION
Resolution
Healing by scarring
Progression to suppuration
Progression to chronic inflammation

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INFLAMMATION OUTCOME
Acute
Inflammation
Resolution/Healing
Chronic
Inflammation
Abscess
SinusFistula
Ulcer
Injury

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