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Inflammation Acute and chronic PowerPoint Presentation (1)

Part I:
Inflammation- Acute
By Amol There
Cardinal signs of inflammation
Stimuli for acute inflammation
Acute vs chronic inflammation
Events in acute inflammation
Chemical mediators in inflammation
Is defined as the local response of living mammalian tissue
to injury from any agent.
It is a body defense reaction in order to eliminate or limit
the spread of injurious agents, followed by removal of the
necrosal cells and tissue
Inflammation_Cardinal Signs
4 cardinal Signs of inflammation:
The roman writer celsus in 1st centurary A.D. named the famous
signs of inflammation as:
Functio laesa(Loss of function) later added by virchow.
The injurious agents:
Infective agents :- bacteria, viruses and their toxins, fungi, parasites.
Immunological agents:- cell mediated and antigen-antibody reactions.
Physical agents:- heat, cold, radiations mechanical trauma.
chemical agents:-organic and inorganic poisons.
Inert materials :- as foreign bodies(dirt, splinters, sutures).
Tissue necrosis from any cause
Depending upon the defense capacity of the host
and duration of response, classified as
A. Acute
B. Chronic
Inflammation- Types
A. Acute:- is of short duration( >2 weeks), representing early body
reaction, resolve quickly and usually followed by healing.
Main features:Accumulation of fluid and plasma at the affected site.
Intravascular activation of platelets.
Migration of leucocyte-neutrophils.
B. Chronic: is of longer duration and occurs after delay, either after the
causative agents of acute inflammation persists for a long time or
the stimulus is such that it induces chronic inflammation from the
Marked chiefly by the formation of new connective tissue.
Inflammation_Acute Inf.
Two events:
A. Vascular
B. Cellular
Alteration in the microvasculature(arterioles, capillaries and
venules) is the earliest response to tissue injury.
These alterations include Hemodynamic changes and
changes in vascular permeability.
Emigration of leucocyte from the microcirculation and
accumulation in the focus of injury(cell recruitment and
Inflammation_Acute Inf.
A. Vascular Changes:
Starling’s Law:
Movements of fluid in and out of arterioles, capillaries and venules is
regulated by the balance between.
1. Intravascular hydrostatic pressure- tends to force fluid out of vessels
2. Osmotic pressure of the plasma proteins- tends to retain fluid within
the vessels.
Forces that cause outward movements of fluid from microcirculation;
Intravascular Hydrostatic pressure and colloidal osmotic pressure of
interstitial fluid.
Forces that cause inward movement of interstitial fluid into circulation:
Intravasculature colloid osmotic pressure and hydrostatic pressure of
interstitial fluid.
In Inflamed Tissue:
There is a accumulation of edema fluid in the interstitial compartment
which comes from blood plasma initially the fluid escape due to
vasodilation and consequent elevation in hydrostatic pressure.
The endothelial lining of microvasculature becomes more leaky.
Consequently, intravascular colloid osmotic pressure decreases and
osmotic pressure of the interstitial fluid increases resulting in
excessive outward flow of fluid into the interstitial compartment
which is exudative inflammatory edema.
Inflammation_Acute Inf.
Pattern of increased vascular permeability: Increased vascular permeability
via non permeable endothelial layer of microvasculature becomes leaky
can have following pattern and mechanism.
1. Contraction of endothelial cells: An example of such immediate transient
response is mild thermal injury of skin of forearm.
2. Contraction or mild endothelial damage: Classic example of delayed and
prolonged leakage is appearance of sunburns mediated by ultraviolet
3. Direct injury to endothelial cells: The example of immediate sustained
leakage are severe bacterial infections while delayed prolonged leakage
may occur following moderate thermal injury and radiation injury.
4. Leucocyte- mediated endothelial injury: The example are seen in sites
where leucocytes adhere to the vasculature endothelium e.g. in pulmonary
venules and capillaries.
5. leakiness in neovascularization: In addition, angiogenesis under the
influence of vascular endothelial growth factor during the process of repair
and in tumors are excessively leaky.
Cellular Events:- Two processes
1. Exudation of leucocyte
2. Phagocytosis
Exudation of leucocytes:-escape of leucocyte from the
microvasculature to the interstitial tissue. In acute inflammation,
neutrophil comprise the first line defense followed later by the
monocyte and macrophages.
Changes leading to migration of leucocyte are as follows:
Changes in the formed elements of blood
● Rolling and adhesion
● Emigration
● Chemotaxis
● Phagocytosis
Changes in the formed elements of blood :1. Early stage of inflammation , vasodilation progresses but
subsequently, there is slowing of blood or stasis of blood stream.
2. the central stream of cells becomes widen and peripheral plasma
zone becomes narrower because of loss of plasma by
exudation. This phenomenon is known as Margination or
peripheral orientation.
3. As a result of this redistribution neutrophil of the central column
come to the vessel wall, this known as Pavementing.
Rolling and Adhesion:
Neutrophil slowly roll over the endothelial cells(roll over), followed
by transient bond(adhesion phase), cell adhesion molecules which
brings rolling and adhesion.
Selectin (P,E,L):Expressed on the surface of activated Endothelial cell
which brings out the rolling of leucocyte.
Integrins : Endothelial cell surface protein, which are activated during
the process, loose and transient adhesion between leucocyte and EC.
Immunoglobulin: Present on most cells, partake in cell to cell contact
through various CAM and cytokines.
Emigration: 1. After sticking of neutrophil to endothelium,
2. Throw out cytoplasmic pseudopods.
- In first 24 h(half life-24-48 h)
- Monocyte- Macrophages appear in the next new 24-48 h and survive
much longer.
Chemotaxis: Transmigration of leucocytes after crossing several barriers
(endothelium, basement membrane, perivascular myofibrobalsts and
matric) to reach the interstitial tissue is a chemotactic factor mediated
Chemotactic agents for neutophils --Leukotriene B4(LT-B4)
--Complement system(C5a and C3 a)
--Cytokine(Interleukin, IL-1,8)
--Soluble bacterial products(such as formylated peptide)
Phagocytosis: is defined as the process of engulfment
particulate material by the cells.
of solid
Neutrophil and macrophages on reaching the tissue spaces produces
several proteolytic enzymes- lysozyme, protease, collagenase,
elastase, lipase, proteinase, gelatinase and acid hydrolase.
Enzyme degrade collagen and extracellular matrix.
Phagocytosis of microbe.
1.Recognition and attachment
3. Killing and Degradation
1.Recognition and attachment:- expression of cell surface receptor
on macrophages –Mannose and scavenger.
Further enhanced by opsonization (microbes coated with opsonins
protein from serum)
2.Engulfment:- The opsonized particle or microbe bound to the
surface of phagocyte is ready to be engulfed. Pseudopods formation
through activation of actin filament- phagocytic vacuole.
3. Killing and Degradation:- phagocytes and scavenger cells
function-degradation of microorganism.
Disposal of micro-organism take pace by two mechanisms
A. A. Intracellular Mechanisms
B. Extracellular Mechanisms
A-Intracellular Mechanisms- intracellular metabolic pathways- by oxidative, common
- Less often by non-oxidative
1. Oxidative bactericidal mechanism by oxygen free radicals-oxidative
damage by O-2,H2O2,OH-,HOCl,HOBr. Either via Myeloperoxidase or
2. Oxidative bactericidal mechanism by lysosomal granules-preformed
granule-stored of neutrophil and macrophages are discharged into the
phagosome and extracellular environment.
3. Non-oxidative bactericidal mechanism-.
some agents released from phagocytic cell do not require oxygen for
bactricidal activity- Nitric oxide.
B. Extracellular:
i)Granules- Degranulation of macrophages and neutrophil –exerts
effects of proteolysis outside the cells as well apart to above.
ii) Immune mechanism- immune- mediated lysis of microbe take
place outside the cells by mechanism
------Antibody-mediated lysis
-------By cell-mediated cytotoxicity.
Inflammatory Mediators
Mediators of inflammation - release to certain stimuli- may be
injurious agents, dead cell, damaged cell.
1) Cell derived mediators
A. Vasoactive amines
2)Plasma protein derived
mediators (plasma proteases)
A. Kinin system
B. Arachidonic acid metabolite
C. Lysosomal components
B. Clotting System
D. Platelet Activating Factor
C. Fibrinogen System
E. Cytokines
D. Complement Cascade
F. Free radicals
Mediators of inflammation - release to certain stimuli- may be
injurious agents, dead cell, damaged cell.
Two types
1) Cell derived mediators
2) Plasma protein derived mediators(plasma proteases)
1) Cell derived mediators are:A. Vasoactive mediators
1. Histamine-granules in mast cell, basophil and platelet.
2. 5_HT-tissue like chromaffin cell of GIT, NT, mast cell & platelet.
3. Neuropeptides-Substance P, Neurokinin, VIP and somatostatin.
B. Arachidonic acid metabolite –
Arachidonic acid Derived from cell membrane by phospholipase.
It is then activated to archidonic acid metabolite by two pathways
1. cyclooxygenase pathway:
Cell membrane ( phospholipid)-----→Archidonic acid -------- PGG2PL ase
-----→PGH2-------→ 3 metabolite
a) Prostaglandin(PGD2,PGE2,PGF2-alpha)
b) Thrombooxane A2
c) Prostacyclin
2. Metabolite via lipo oxygenase pathway: 5-HETE, leukotrienes
Lipooxgenase in neutrophil act on Arachinodic acid---→5-HPETE-→peroxidation to form 3 metabolites------5-HETE(CT agent),
leukotrienes A4----LTB4(CT and cell adherence), LTC4, LTD4, and
LTE4common action by causing smooth muscle contraction and thereby
induce vasoconstriction, broncho-constriction and increased vascular
3.Lipoxin-regulate and counterbalance action of LT A.
C. Lysosomal components:- the inflammatory cells-neutrophil and monocyte,
contain lysosomal granules
1. Granules of neutrophil- 3 types of granule- 1ary,2ndary and 3tiary
2. granules of monocyte and tissue macrophages-on degranulation release
proteases, collagenase, elastase and plasminogen activator.
D. Platelet Activating Factor(PAF)-IgE-sensitised basophil or mast
cell, leucocyte, endothelium and platelet.
Apart to platelet aggregation, PAF as mediator of inflammation are:
Increase vascular permeability
Vasodilation in low con and vasoconstriction
Adhesion of leucocyte to endothelium
E. Cytokines- polypeptide substances produced by activated lymphocyte and
activated monocyte
i. Interleukins(IL-1,6,8,12,17)1.IL-1 and 6 are active in mediating acute inflammation
2.IL-12 and 17 a potent role in chronic inflammation
3.IL-8 chemotactic for acute inflammatory cells
ii. Tumor necrosis factor (TNF-α and β)- former is a mediator of acute
inflammation and latter is involved in cellular toxicity and in development of
spleen and lymph node.
TNF gama- it is produced by T cells and NK cells and act on all cell.
it acts as mediator of acute inflammation.
iii. Other chemokine- IL-8 MCP-1 PF-4
F. Free radicals: oxygen metabolites and nitric oxide: free radicals acts as
potent mediator of inflammation.
i. Oxygen derived metabolites are released from activated neutrophil and
macrophages and include superoxide oxygen O-2, H2O2,OH- and toxic
Action of inflammation as follows:
----Endothelial cell damage and thereby increased vascular permeability.
---Activation of protease and inactivation of antiprotease causing tissue
----Damage to other cell.
ii. NO- role in mediating inflammation
-- vasodilation
-- antiplatelet activating agent
-- possibly microbicidal action.
B. Plasma Proteins-Derived mediators
These include four systems: Kinin, clotting, fibrinogen and complement
All linked by initial activation of hageman factor XIIa
1. The Kinin System: XIIa generated bradykinin, slow contraction produced
of smooth muscle .
Acts in early stage of inflammation.
Smooth muscle contraction
Increased vascular permeability
2. Clotting system:
factor XIIa initiate the cascade of clotting system resulting in
formation of fibrinogen which is acted upon by thrombin to form
The action of fibrinopeptides in inflammation are:
● Increased vascular permeability
● Chemotaxis for leucocyte
● Anticoagulant activity.
3. Fibrinolytic System:- This system activated by plasminogen
The source of which include kallikrein of the kinin system, endothelial
cells and leucocytes.
The action of plasmin in inflammation are as follows:
i) Activation factor XII to form prekallilrein activator that stimulate
the kinin system to generate bradykinin.
ii) Split of complement C3 to C3a which is a permeability factor
iii) Degrades fibrin to form fibrin split product.
4. The complement system: activation of complement system can
occur either
i. Classic pathway through antigen-antibody complex
ii. Alternate pathway nonimunologic agent such as bacteria, toxin ,
cobra venom and IgA.
Yields of the activation of these pathways which include
anaphylatoxin(c3a,C4a and c5a) and membrane attack
complex(MAC) ie.C5b,C6,7,8,9
The action of Activated complement system in inflammation:
i. C3a, C5a,C4a-activate mast cell and basophil-----cause release of
VA amines--cause increased vascular permeability--cause edema---augments phagocytosis.
ii. C3b is an opsonin
iii. C5a is chemotactic for leucocyte.
iv. Membrane attack complex is lipid dissolving agent and cause hole
in phospholipd membrane.
Factor XII
• Which of the complement components act as
A. C3b
B. C4b C. C5a D. C4a
• The following adhesion molecules play a significant
role in rolling of PMNs over endothelial cells except.
A. Selectins
B. Integrins
C. Opsonins
D. Immunoglobulin molecules
Part II:
Chronic Inflammation
By Amol There
Prolonged process in which tissue destruction and inflammation
occur at the same time.
Chronic inflammation may occur by one of the following 3 ways.
1. Chronic inflammation following acute inflammation
Recurrent attacks of acute inflammation
Chronic inflammation starting de novo
1. Chronic inflammation following acute inflammation
--- when tissue destruction is extensive or
bacteria survive and persist in small no. at the site of acute
e.g. osteomylitis, Pneumonia terminating in lung abscess
2.Recurrent attacks- when repeated bouts of acute infection
culminate in chronicity of the process e,g. chronic
pyelonephritis due to repeated urinary tract infection.
3. De novo--- when the infection with organism of low
pathogenecity is chronic from the beginning e.g, infection with
mycobacterium tuberculosis.
General feature of chronic inflammation:
there are some basic similarities amongst various types of chronic
1. Mononuclear cell infiltration
:infiltrated by mononuclear cells like phagocyte and lymphoid
Monocyte--- to macrophages (beside phagocytosis) ---- further
activated by cytokine.
Other cells are lymphocyte, plasma cell, eosinophil and bacterial
2. Tissue Destruction or necrosis:
brought about by activated macrophages which release a variety of
bilogical active substances.
3. Proliferative changes:As a results of necrosis, of small blood vessel and fibroblasts is
stimulated resulting in formation of inflammatory granulation
Finally, healing by fibrosis and collagen laying take place
Systemic effect of chronic inflammation:
ESR is elevated
Types of chronic inflammation
1. Chronic non-specific inflammation
2. Chronic granulomatous
Types of chronic inflammation
1. Chronic non-specific inflammation
when the irritant substance produces a non- specific chronic
inflammatory reaction with formation of granulation tissue and
healing by fibrosis.
Ex. Chronic osteomyelitis, chronic ulcer, lung abscess.
2. Chronic granulomatous inflammation: in this, the injurious
agent causes a characteristic histological tissue response by
formation of granulomas
Ex. tuberculosis, leprosy, syphilis, sarcoidosis etc.
Granulomatous inflammation:
Defined as circumscribed tiny lesion of 1 mm in diameter,
composed mainly of modified macrophages called epitheloid cells,
and rimmed at the periphery by lymphoid cells.
-Formation of granuloma is type IV granulomatous hypersensitivity
-protective defense reaction by the host but eventually causes
tissue destruction because of persistence of the poorly digestible
antigen e.g. mycobacterium tuberculosis, M. leprae.
Sequence in evolution of granuloma is outlined below:
1. Engulfment by macrophage
2. CD4 + T cells
3. Cytokines
1. Engulfment by Macrophages:- macrophages and monocyte
engulf antigen and try to destroy it.
2. CD4 + T cell – macrophages, being antigen presenting cells, fail
to deal with antigen, present to the CD4 + T lymphocyte.
3. Cytokines- formed by the activated CD4 + t cells and also by
activated macrophges .
Cytokine roles
1. IL-1 & 2 stimulate proliferation of more T cells.
2. Interferon- gamma activates macrophages.
3. TNF-α
endothelium to secrete prostaglandin, which have role in
vascular response in inflammation.
4. growth factors (Platelet- derived growth factor) elaborate by
macrophages stimulate fibroblasts growth.
Ganuloma formed having macrophage modified as epitheloid cells
in the center, with some interspersed multinucleate giant cells
surrounded periphery by lymphocyte and healing by fibroblasts or
Q. Formation of granuloma is
A.Type I hypersensitivity
B. Type II hypersensitivity
C.Type III hypersensitivity
D. Type IV hypersensitivity
Part III:
Basic Principles of
Wound Healing in Skin
By Amol W. There
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