Transcript Acute inflammation

Inflammation
Dr. Samar Saleh
Pathology Department
Faculty of Medicine
University of Mosul
Definition of INFLAMMATION
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Inflammation is the response of living
tissues to cell injury.
Its purpose is to localize & eliminate the
causative agent, to limit tissue injury & then to
restore the tissue to normality or as close to
normality as possible.
It is often beneficial, but sometime harmful.
The nomenclature used to describe
inflammation in different tissues employs the
tissue name and the suffix
◦ Appendicitis
,Dermatitis
,lung , brain …..ect.
“-itis”
e.g.,
,Cholecystitis , hepatitis
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Rubor = redness due to V.D.
Tumor = swelling due to exudate.
Calor = heat due to V.D.
Dolor = pain due to secretion of
PG,BK & nerve compression &
irritation.
(described by Celsus 1st. Century AD)
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Functio laesa = loss of function due
to pain & swelling i.e. reflux
immobilization due to pain.
(added by R. Virchow)
Cellulits = acute skin infection commonly caused
by Streptococcus pyogenes or Staphylococcus
aureus
Causes of Inflammation:
1.Infections:e.g., bacterial, viral, parasitic fungal
…..
2.Physical agents: e.g., heat, cold, radiation…….
3.Chemical agents: e.g., acid, alkaline, drugs……..
4.Hypersensitivity: e.g., rheumatic fever………..
5.Tissue necrosis: e.g., Ischemic necrosis.
Components involved in
inflammation
 Blood
vessels.
 Plasma & plasma proteins.
 Cells
◦ Circulating cells include :Neutrophiles,
Monocytes, L, E, B, & plasma cells.
◦ Connective tissue cell include : mast cells,
fibroblasts, Macrophage & Lymphocytes.
 Extra-celluar
matrix
◦ Collagen, elastic tissue, adhesive glycoproteins,
protoglycans & basement membrane.
Types of inflammation
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1.Acute inflammation.
2.Chronic inflammation.
3. Acute on chronic inflammation.
Acute inflammation
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Short duration: hours
-days –weeks.
Exudative fluid
(protein rich fluid +
inflammatory cells +
debris).
Main inflammatory
cells
◦ Neutrophile &
Macrophage.
Chronic inflammation
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Long duration: months
– years.
Fibrosis ( productive ).
Main inflammatory
cells
◦ L, M, plasma cells +
fibroblasts & endothelial
cells.
 Definitions:
◦ Edema: excess fluid in interstitial tissue or body cavities.
May be either an exudate or transudate
◦ Exudate: an inflammatory extravascular fluid that has a high
protein concentration( 35-50 gm/l), cellular debris, and a
specific gravity above 1.020.
◦ Transudate: an extravascular fluid with low protein content
and a specific gravity of less than 1.015.essentially an
ultrafiltrate of blood plasma resulting from eleveted
hydrostatic pressure or diminished osmotic forces in the
plasma.
◦ Pus (purulent exudate):
an inflammatory exudate rich in leukocytes (mostly
neutrophils), cellular debris, and in many cases
microbes.
Vascular changes and fluid leakage during acute inflammation lead to
Edema in a process called Exudation
Transudate
•result of hydrostatic
or osmotic imbalance
•ultrafiltrate of plasma
•Low protein content
•specific gravity < 1.015
Exudate
•result of inflammation
•vascular permeability
•high protein content
•specific gravity >1.020
Exudate
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Due to increase vascular permeability
induced by chemical mediators and due to
the direct damage of the vessels, excessive
fluid passes to the extra-cellular spaces
result in edema.
It is consist of:
◦ 1.Fluid rich in plasma proteins.
◦ 2.Fibrin.
◦ 3.Cells: Neutrophils, Macrophages, eosinophils, few
lymphocytes & red blood cells.
◦ 4.Debris.
What are the function of
EXUDATE?
◦ 1.It dilutes toxins.
◦ 2.It contains fibrin which localize
infection.
◦ 3.It carries oxygen, nutrients to the
inflammatory cells.
◦ 4.It carries Drugs, antibodies against
bacteria.
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It may have harmful effects e.g. causing lifethreatening hypersensitivity reactions, or
relentless and progressive organ damage from
chronic inflammation and subsequent fibrosis (
e.g. rheumatoid arthritis, atherosclerosis).
Acute inflammation
It is the response of living vascularised tissue
to injury .
This response is:
1.Uniform,
2.Last for short time.
3.Characterised by exudation of fluid
(Edema) and cells (Neutrophile).
 Neutrophiles are predominant inflammatory
cells in early stages (6 - 24 hours).
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Monocytes ( macrophages) predominate
inflammatory cells in later stages (24 - 48
hours).
Processes of acute inflammatory
response
I- Vascular changes
◦ Alteration in vascular caliber resulting in local
increase in blood flow.
◦ Structural changes resulting in increase vascular
permeability.
II- Leukocyte cellular events
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Margination or pavementation & rolling
Adhesion & transmigration.
Chemotaxis & activation.
Phagocytosis & degranulation.
Release of leukocyte products.
Chemotaxis & activation
◦ Chemotaxis:controled movement of WBCs toward a
chemical gradient known as chemotaxins.
◦ Chemotaxins:The substance which induce (stimulate)
chemotaxis e.g. bacteria, chemical mediators……….
◦ Types of chemotaxins:
 Exogenous: bacterial products
 Endogenous:
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C5a (complement factor)
LTB4 (lipo-oxygenase pathway)
IL-8 (Cytokines)
PAF (platelate activating factor)
Phagocytosis & degranulation
By neutrophiles & macrophages.
 Three steps
1-Recognition & attachment
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◦ facilitated by coating of microorganisms by serum
proteins called OPSONINS. Mainly IgG & C3b that bind to
Fc & C receptors on the WBC.
2-Engulfment
◦ through formation of pseudopodia, phagosome,
phagolysosome.
3-Killing or degradation
◦ through formation of free radicals (Superoxides,
hydrogen peroxide (H2O2) & hydrochloride (HOCL) ).
Release of leukocyte products
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These include:
◦ Lysosomal enzymes (protease).
◦ Oxygen-derived active metabolites (free radicals).
◦ Products of Arachidonic acid metabolism (lipooxygenase & cyclo-oxygenase products) .
Leukocytes extra-vasation have critical
function in inflammation it:
 1.Ingest offending agents.
 2. Kill bacteria.
 3.Digest necrotic materials.
 4.Release lysosomal enzymes.
 5.Release free radicles.
 6. Release chemical mediators.
Passage of RBCs through the defect created by
the WBCs.
It is a passive process.
Transient vasoconstrictionProlonged
vasodilatationIncreased blood flow (Active
hyperemia  increased vascular
permeability-Stasis of blood Swelling of
endothelial cells  margination or
pavementation of WBC Exudation of WBC
(emigration) and passage of RBC(Diapedesis)
& exudation of fluid.
Chemical Mediators
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A substances which play a role in genesis and
modulation of inflammatory reaction.
They are responsible for:
◦ 1.Vasodilatation.
◦ 2.Increased permeability of the blood
vessels.
◦ 3.Emigration of WBC (Chemotactic agent).
1.Those formed in plasma
2.Those formed in tissue cells.
Plasma factors synthesized mainly in liver
Factor XII =
coagulation system
(Hageman factor)
activation
Kinin system
Coagulation
system
Plasma proteins
C3a
C5a
Complement
activation
C3b
C5b-C9
anaphylatoxins
opsonin
MAC
Chemical Mediators of Inflammation
A/ Vasoactive Amines
1) Histamine: secreted from mast cells,
basophiles & platelets.
2) Serotonin: secreted from platelets,
enterochromaffin cells.
Effects: arteriolar vasodilatation & increase
vascular permeability.
B/ Arachidonic Acid (AA) Metabolites
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AA present in the cell membrane phospholipids.
Release from phospholipids through the action
of phospholipase enzyme by mechanical,
chemical & physical stimuli.
AA metabolism proceeds along one of two
pathways
◦ Cyclo-oxygenase pathway--- Postoglandins (PG)
◦ Lipo-oxygenase pathway------Leukotriens (LT)
Cyclo-oxygenase
pathway
Lipo-oxygenase
pathway
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Thromboxane A2
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5-HETE:
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Protacyclin (PGI2)
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LTB4:
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PGD2, PGE2 & PGF2
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LTC4, LTD4, LTE4
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PGE2:
◦ Vasoconstriction
◦ Platelet aggregation
◦ Vasodilatation
◦ Inhibits Platelet
aggregation
◦ VD & edema
◦ Fever
◦ Pain
◦ Chemotaxis
◦ Chemotaxis
◦ Aggregation of
neutrophils
◦ Vasoconstriction
◦ Bronchospasm
◦ Increase vascular
permeability
C/ Platelet-Activating Factor (PAF)
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Synthesized from membrane phospholipids
through the action of phospholipase A2 in
basophiles, endothelial cells & neutrophiles.
Effect:
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Platelet aggregation.
V.D. & increase vascular permeability.
Chemotaxis.
Smooth muscle contraction.
D) Cytokines
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Polypeptides produced by activated
lymphocytes & macrophages.
It involved in cellular immunity &
inflammatory responses.
◦ IL-1 & TNF
 Acute phase reaction including fever & Neutrophilia.
 Promote endothelial secretion of PG & NO.
 Induce fibroblastic proliferation & collagen synthesis.
◦ IT-6
 Acute phase reactions.
◦ IT-8
 Chemotactant & neutrophiles activating agent.
E) Nitric Oxide (NO)
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Soluble free radical gas synthesized by
endothelial cells, macrophages & specific
neurons in the brain.
Effects of the Nitric Oxide:
◦ Vascular smooth muscle relaxation causing
vasodilatation.
◦ Decreased platelet aggregation & adhesion.
◦ Microbicidal agent.
F) Lysosomal Constituents
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Potentially act as inflammatory mediators
when released from neutrophiles &
macrophages.
 Effect:
◦ Destruction of ECM.
◦ Direct cleavage of C3 & C5.
G) Oxygen Free Radicals
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Superoxide (O2-), OH-, H2O2 & NO
 Effects:
◦ Endothelial cell damage causing increase vascular
permeability.
◦ Activation of proteinases.
◦ Injury to surrounding cells.
H/ Plasma Proteases
1)Complement System
 Present as inactive form in the plasma
◦ Vascular effect (anaphylotaxins):
C3a, C5a & C4a causing V.D. & increase vascular
permeability.
◦ Leukocyte adhesion, chemotaxis & activation: C5a
◦ Phagocytosis:
C3b & C3b1 act as opsonin.
2) Kinin System
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Activated by activation of Hageman factor (XII)
◦ Bradykinin: increase vascular permeability , V.D., pain
& smooth muscle contraction.
◦ Kallikrein: has chemotactic activity.
3) Clotting System
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A cascade activated by Hageman factor (XII)
resulting in conversion of fibrinogen to
fibrin.
◦ Fibrinopeptides: increase vascular permeability &
chemotaxis.
4) Fibrinolytic System:
◦ Plasmin: lyses fibrin clots, degrades fibrin to
fibrin degradation products.
◦ Fibrin degradation products: Increase vascular
permeability.
Microscopic appearance of acute inflammation
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Congestion of blood vessels.
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Exudation of fluid.
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Exudation of inflammatory cells mainly
neutrophiles.
Macroscopic types of acute inflammation
1. Cattarhal
◦ Acute inflammation + mucus hypersecretion of mucus
membrane (common cold).
2. Serous
◦ Low protein content, low cellular fluid (pleural effusion).
3. Suppurative (Purulent)
◦ Pus: creamy yellow or blood stained fluid consist of N,
M.O., & tissue debris (acute appendicitis).
◦ Abscess: localized collection of pus material.
◦ Empyema: Collection of pus in the hallow organ.
4. Fibrinous
◦ Accumulation of thick exudate rich in fibrin, which may
resolve by fibrinolysis or organize into thick fibrous
tissue. Fibrinous inflammation –bread &butter appearance to the
inflamed serous membrane.
Serous inflammation:
Tissue fluid accumulation indicating a modest
increase in vascular permeability
Pleura, pericardium,
peritoneum: effusion
,Blister in burns
 Fibrinous inflammation:
 More marked increase in vascular permeability,
with exudates containing large amounts of
fibrinogen
 Involvement of serosal surfaces ( pericardium or
pleura) : fibrinous pericarditis or pleuritis
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Suppurative or purulent inflammation:
Production of purulent exudates consisting of
leukocytes and necrotic cells.
What’s the fates (outcomes) of acute inflammation?
Depending on the nature of lesion, site & response
of the host.
The followings are the outcome of acute
inflammation:
1-Complete resolution: restoration of site of acute
inflammation to normal. It involve:
◦ removal of the exudate, fibrin & debris.
◦ reversal of the microvascular changes.
◦ regeneration of lost cells.
Fates (outcomes) of acute inflammation (cont.)
2-Healing & organization: replacement of dead
tissue by granulation tissue which
mature in to fibrous tissue.
It is seen in chronic inflammation, In excessive
tissue damage & excessive fibrin deposition.
3-Suppuration It may be diffuse in tissue,
localized in tissue (abscess) , on the surface of
a wound, or in serous cavity.
4-Progression to chronic inflammation:
Acute inflammation progress in to chronic
inflammation when there is persistent infection,
when there is foreign body…………….
Ulcer:
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Local erosions ( Loss of continuity ) of
epithelial surfaces produced by sloughing of
inflamed necrotic tissue.
Role of lymphatic system in
inflammation
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The local inflammatory reaction may fail in
containing the injurious agent
Secondary lines of defense
◦ Lymphatic system; causing
 lymphangitis (lymphatic vessels inflammation)
 lymphadenitis (lymph nodes inflammation)
◦ Monocytic-phagocytic system; involve
 phagocytic cells of spleen, liver & Bone marrow.
BENIFITIAL effect
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Dilution of toxins
Entry of antibodies
Drug transport
Fibrin formation
Delivery of nutrient &
O2
Stimulation of
immune system
HARMFUL effect
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Digestion of normal
tissue
Swelling & pain
Inappropriate
inflammatory
response.