Transcript Inflammation 1

Inflammation
Dr. Ahmad Hameed
MBBS,DCP, M.Phil
Definition
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Inflammation is a protective response involving
host cells, blood vessels, proteins and other
mediators intended to eliminate the initial cause
of cell injury, as well as the necrotic cells and
tissues resulting from the original insult, and to
initiate the process of repair.
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Although inflammation helps clear
infections and other noxious stimuli and
initiates repair, the inflammatory reaction
and the subsequent repair process can
themselves cause considerable harm.
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The cells and molecules of host defense,
including leukocytes and plasma proteins,
normally circulate in the blood and the goal of
the inflammatory reaction is to be bring them to
the site of infection or tissue damage.
Features of Acute and Chronic Inflammation
Feature
Acute
Chronic
Onset
Fast: minutes or hours
Slow, days
Cellular Infiltrate
Mainly neutrophils
Monocytes/macrophages
and lymphocytes
Tissue injury, fibrosis
Usually mild and selflimited
Often severe and
progressive
Local and systemic signs Prominent
Less prominent; may be
subtle
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Inflammation is induced by chemical
mediators that are produced by host cells in
response to injurious stimuli.
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Macrophages, dendritic cells, mast cells
Also produced from plasma proteins
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The components of acute and chronic inflammatory responses and
their principal functions.
Cardinal Signs
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These signs are:
rubor (redness)
 tumor (swelling)
 calor (heat)
 dolor (pain)
 functio laesa, or loss of function
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Inflammation is normally controlled
and self limited
Acute inflamation
Two major components
VASCULAR CHANGES
Vasodilation
 Increased vascular permeability
CELLULAR EVENTS
 Recruitment
 Activation, in acute inflammation (neutrophils)
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Stimuli for Acute Inflammation
CAUSES
 Infections: bacteria, viruses, parasites
 Trauma: (blunt and pentrating) Physical and chemical
agents
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Tissue necrosis: myocardial infarct
Foreign bodies:
Immune reactions:
Recognition of Microbes, Necrotic Cells
and Foreign Substances
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Phagocytes, dentritic cells, epithelial cells
express “pattern recognition receptors”
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Toll like receptors (TLRs)
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Ten mammalian TLRs
Inflammasome
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Products of dead cell
Activates caspase-1
IL-1
IL-1 plays a role in atherosclerosis, obesity associated
type 2 diabetes
Possibility of treating these diseases by blocking IL-1
Vascular Changes
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Changes in vascular caliber and flow
VASOCONSTRICTION
(momentary constriction of small BV).
 Vascular spasm begins very quickly (30 sec.) after the
injury at it last a few minutes.
 The mechanism of spasm is nervous – through
catecholamine liberated from sympathetic nerves
endings.
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ACTIVE VASODILATION
(through catabolism products that act through receptors
and directly stimulates vascular dilation – nervous
mechanism).
 Dilation of arterioles and capillaries (redness =
rubor);
 Blood flow increases and gives pulsate sensation;
 Active hyperemia in skin territory and increased
metabolism leads to higher local temperature (heat =
calor).
INCREASED VASCULAR PERMEABILITY
Blood vessels in the affected area loose their
reactivity to nervous and humoral stimuli and
passive vasodilation occurs.
 Progressively fluid move into the tissues
cause swelling (tumor), pain, and impaired
function.
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Exudate
Transudate
Edema
MECHANISMS CONTRIBUTING INCREASED
PERMEABILITY
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Endothelial “gaps”
Direct Injury, Leukocyte Injury
Transocytosis
New Vessels
All of them may participate in response to
particular stimulus
Endothelial cell contraction leading to
intercellular gaps in postcapillary venules
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Short-lived (15-30) minutes
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Histamine, bradykinin, leukotrienes, and others
Slower and prolonged (6-24) hours
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TNF, IL-1
Endothelial injury
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Burns, some infections
Venules, capillaries, and arterioles can all be
affected
Delayed prolonged leakage
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Thermal injury
Bactrical toxins,
Ultraviolet irradiation
Activated leukocytes release many toxic
mediators
Increased trancytosis
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VEGF
Transcytosis occurs through channels formed by
fusion of intracellular vesicles
Leakage from new blood vessels
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These vessel sprouts remain leaky until
proliferating endothelial cells mature sufficiently
to form intercellular junctions.
VEGF
Response of lymphatic vessels
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Increased lymph flow  drain edema fluid 
also transports leukocytes, cell debris and
maybe offending agent
Offending agent  lymphangitis 
lymphadenitis
Clinically: Presence of red streaks near wound
indicates infection of wound