Download Inflammation

Manar Hajeer, MD, FRCPath
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Protective response involving host cells, blood vessels, and proteins
and other mediators that is 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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Without inflammation, infections would go unchecked and wounds
would never heal.
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However, can cause considerable harm (if strong, prolonged or
inappropriate)
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Leukocytes
Plasma proteins and mediators
Blood vessels
ECM
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Inflammation is normally controlled and self-limited.
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The outcomes of acute inflammation
Elimination of the noxious stimulus.
Decline of the reaction and repair of the damaged tissue,
Persistent injury resulting in chronic inflammation.
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Hotness : localized, due to vasodilation.
Fever : systemic, caused by mediators mainly
prostaglandins.
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Hotness is a cardinal sign of inflammation, fever is not!
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Infection can cause inflammation.
Infection is caused by a pathogen.
Inflammation is the protective response that is caused by
infections among other causes.
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Infections
Trauma
Physical and chemical agents
Tissue necrosis
Foreign bodies
Immune reactions
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Tonsillitis
Apendicitis
Pancreatitis
Liver…?
Lung..?
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Acute inflammation
Rapid onset
Short duration
Lasting few minutes to few
days
Exudate
Predominantly neutrophilic.
Prominent signs
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Chronic inflammation
More insidious.
longer duration (days to years)
lymphocytes and
macrophages
Vascular proliferation and
fibrosis (scarring).
Mild signs
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Phagocytes, dendritic cells, express different classes of receptors
that sense the presence of microbes and dead cells.
Called pattern recognition receptors
A, Toll-like receptors (TLRs)
In plasma membrane and endosomes
Ten mammalian TLRs,
Recognize products of bacteria(endotoxin, DNA), viruses (RNA) and
other pathogens
Non specific, defense against all classes of infectious pathogens
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Multi-protein cytoplasmic complex.
Recognizes products of dead cells
(uric acid, ATP, crystals) and some
microbes..
Activates caspase 1upon
stimulation.
Caspase 1activates IL1(inflammatory mediator)
Gout and urate crystals
Atherosclerosis.
DM type 2
Role of IL-1 antagonists
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Vascular changes:
Alterations in vessel caliber resulting in increased blood flow
(vasodilatation) and structural changes that permit plasma proteins
to leave the circulation (increased vascular permeability).
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Cellular events:
Emigration of the leukocytes from the microcirculation and
accumulation in the focus of injury (cellular recruitment and
activation).
The principal leukocytes in acute inflammation are neutrophils.
1- Changes in Vascular Caliber and Flow:
 Transient vasoconstriction (lasting only for seconds)
 Arteriolar vasodilation.
 Capillary and venular vasodilatation.
 Slowing of the circulation and stasis.
 Leukocyte margination.
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NET RESULT HOTTNESS AND REDNESS.
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Affects arterioles
Due to neural reflex
3-5 seconds in mild injuries.
Several minutes in more severe injury (like burns).
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First in arterioles
Then capillaries and venules.
Increasing blood flow.
Hotness and reddness.
Increased local hydrostatic pressure
Transudation of protein poor fluid into the extravascular space
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Leads to peripheral orientation of leukocytes (mainly neutrophils)
along the vascular endothelium [leukocytic margination].
2 - Increased Vascular Permeability:
 increasing vascular permeability that allows the movement of
protein-rich fluid and even cells (exudate)=====EDEMA.
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Components of exudate
◦ Fluid
◦ Fibrin
◦ Cells: neutrophils predominate (6-72 hours), also macrophages
(involved slightly later: 48+ hours)
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TRANSUDATE
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Hydrostatic pressure
imbalance across vascular
endothelium
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Fluid of low protein content
(ultrafiltrate of blood plasma)
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Specific gravity <1.012
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EXUDATE
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Alteration in normal
permeabiltiy of small blood
vessels in area of injury
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Fluid of high protein content
(>3g/dl) & increased cellular
debris
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Specific gravity >1.020
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Endothelial cell contraction (most common), in post capillary
venules. Increases the gaps through which fluid is lost.
Others:
 Endothelial cell retraction.
 Direct endothelial injury.
 Leukocyte-mediated endothelial injury .
 Increased transcytosis of proteins .
 Leakage from new blood vessels.
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Endothelial cell contraction
◦ Reversible
◦ Immediate transient response but short lived (15-30 minutes)
◦ Induced by: histamine, bradykinin, leukotriens, neuropeptide
substance P
◦ Mostly in postcapillary venules
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Endothelial cell retraction
◦ Reversible
◦ Starts 4-6 hours after injury and stays for 24 hours
◦ Induced by: IL-1 and TNF, IFN-g
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Direct endothelial injury
◦ Severe injury. E:g burns or infections
◦ Immediate sustained response
◦ All microvessels can be affected
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Delayed prolonged response:
◦ Begins after delay (2-12 hours), lasts for hours or days
◦ Caused by mild thermal injury, UV radiation, bacterial toxins.
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Increased transcytosis through vesiculovacuolar pathway
◦ Stimulated by VEGF
Leakage from newly formed blood vessels
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