8 Acute Inflammation IW
Transcript of 8 Acute Inflammation IW
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Acute InflammationAcute Inflammation
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Inflammation & HealingInflammation & Healing Recognition of injuryRecognition of injury
Removal of injurious stimulusRemoval of injurious stimulus
Repair of any damageRepair of any damage
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Injurious stimuliInjurious stimuli TraumaTrauma
InfectionInfection
Physical (irradiation, thermal)Physical (irradiation, thermal)
ChemicalChemical IschaemiaIschaemia (lack of blood i.e. oxygen)(lack of blood i.e. oxygen)
Immune reactionsImmune reactions
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Cell Injury
Acute Inflammation
Chronic Inflammation
Healing & Repair
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Acute inflammationAcute inflammation
Stereotyped responseStereotyped response
Delivers molecules and cells to site of Delivers molecules and cells to site of injuryinjury
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Acute inflammationAcute inflammation
Vascular reaction leading to increaseVascular reaction leading to increase
in blood flow, exudation of plasmain blood flow, exudation of plasma
proteins into tissues and emigrationproteins into tissues and emigrationof of neutrophilneutrophil polymorphs into tissuepolymorphs into tissue
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Acute myocardial infarction
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Vascular changesVascular changes
Vasodilatation & increased blood flowVasodilatation & increased blood flow
Increased vascular permeabilityIncreased vascular permeability
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Vascular permeabilityVascular permeability Endothelial cell contractionEndothelial cell contraction
Direct injuryDirect injury
Leukocyte dependent injuryLeukocyte dependent injury
IncreasedIncreased transcytosistranscytosis VascularVascular neogenesisneogenesis
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Increase in vascular permeabilityIncrease in vascular permeability
Loss of Loss of oncoticoncotic pressure in capillariespressure in capillaries
as vessels permeable to proteinas vessels permeable to protein Excess fluid in tissuesExcess fluid in tissues –– oedema fluidoedema fluid
(protein rich(protein rich exudateexudate)) –– swellingswelling Precursors of protein mediatorsPrecursors of protein mediators
FibrinFibrin –– scaffolding forscaffolding for effectoreffector cellscells
ImmunoglobulinsImmunoglobulins
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PolymorphonuclearPolymorphonuclear neutrophilneutrophil
granulocytesgranulocytes
Mediator cellsMediator cells –– release inflammatoryrelease inflammatory
mediatorsmediators
EffectorEffector cellscells –– kill bacteria and fungikill bacteria and fungi
Attracted to site of inflammation andAttracted to site of inflammation and
activated byactivated by chemotacticchemotactic factorsfactors
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How doHow do neutrophilneutrophil polymorphs getpolymorphs get
to site of inflammation?to site of inflammation?
Move in marginal zone of blood flowMove in marginal zone of blood flow
Changes in vessel wallChanges in vessel wall -- integrinsintegrins,,ICAMICAM--1 & VCAM1 & VCAM--1(leukocytes) & 1(leukocytes) &
selectinsselectins (endothelial cells) induced(endothelial cells) inducedby ILby IL--1 & TNF1 & TNF
ChemotaxisChemotaxis in tissuesin tissues
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ChemotacticChemotactic AgentsAgents NN--formylformyl––methioninemethionine peptides frompeptides from
bacteriabacteria C5aC5a
LeukotrieneLeukotriene BB44
ILIL--88
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Leukocyte ActivationLeukocyte Activation Production of Production of arachidonicarachidonic acidacid
metabolitesmetabolites DegranulationDegranulation & activation of & activation of
oxidative burstoxidative burst
Secretion of cytokinesSecretion of cytokines
Modulation of adhesion moleculesModulation of adhesion molecules
Expression of surface receptors forExpression of surface receptors forbacterial products, cytokines, C3b & bacterial products, cytokines, C3b & FcFc
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PhagocytosisPhagocytosis RecognitionRecognition –– lectinslectins (mannose),(mannose), FcFc,,
C3b,C3b, EngulfmentEngulfment
KillingKilling –– oxygen dependentoxygen dependent ––reactive oxygen intermediates (ROI)reactive oxygen intermediates (ROI)
(H(H22OO22 & & myeloperoxidasemyeloperoxidase) : oxygen) : oxygen
independentindependent –– lysosymelysosyme,, elastaseelastase etcetc
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Chemical Mediators ControlChemical Mediators Control
InflammationInflammation
Cell derivedCell derived –– endogenous and newlyendogenous and newlysynthesisedsynthesised
Plasma derivedPlasma derived
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Cell derivedCell derived – – endogenousendogenous
(pre(pre--formed)formed)
Histamine (vasodilator, increasesHistamine (vasodilator, increasesvascular permeability)vascular permeability)–– mast cellsmast cells
SerotoninSerotonin –– plateletsplatelets
LysosomalLysosomal enzymesenzymes –– neutrophilsneutrophils
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Mast cellsMast cells Found along blood vesselsFound along blood vessels
DegranulateDegranulate in response to physicalin response to physicalinjury (heat, cold, trauma), immuneinjury (heat, cold, trauma), immune
reactions (reactions (
IgEIgE
), C3a & C5a,), C3a & C5a,
cytokines (ILcytokines (IL--1 & IL1 & IL--8), etc.8), etc.
“ “SentinelSentinel” ” cellscells
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Newly synthesised mediatorsNewly synthesised mediators ArachidonicArachidonic acid metabolitesacid metabolites ––
prostaglandins,prostaglandins, thromboxanesthromboxanes,,leukotrienesleukotrienes,, lipoxins.(celllipoxins.(cellmembranes)membranes)
Platelet activating factor (mast cells)Platelet activating factor (mast cells) Tumour necrosis factor, ILTumour necrosis factor, IL--11
(macrophages)(macrophages)
Nitric oxide (leukocytes)Nitric oxide (leukocytes)
Oxygen metabolites (leukocytes)Oxygen metabolites (leukocytes)
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Plasma enzyme cascadesPlasma enzyme cascades
preformed in bloodpreformed in blood
ClottingClotting
FibrinolysisFibrinolysis
ComplementComplement
KininKinin
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Plasma Enzyme CascadesPlasma Enzyme Cascades
enzyme A
Inactive enzyme B Active enzyme B + fragment B
Inactive enzyme C Active enzyme C + fragment C
Inactive enzyme D Active enzyme D + fragment D
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XIIa
Coagulation:fibrinopeptides
Kinin system:
Bradykinin
Fibrinolysis:Fibrin degradation products
Complement:
C3a, C5a, MAC
kallikrein
plasmin thrombin
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VasodilatationVasodilatation ProstaglandinsProstaglandins
Nitric oxideNitric oxide
HistamineHistamine
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Increased vascular permeabilityIncreased vascular permeability Histamine & serotoninHistamine & serotonin
C3a & C5aC3a & C5a
BradykininBradykinin
LTCLTC44, LTD, LTD44, LTE, LTE44
PAFPAF
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ChemotaxisChemotaxis C5aC5a
LTBLTB44
ILIL--1, TNF1, TNF
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FeverFever ILIL--11
TNFTNF
ProstaglandinsProstaglandins
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PainPain ProstaglandinsProstaglandins
BradykininBradykinin
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Tissue damageTissue damage NeutrophilNeutrophil & macrophage& macrophage lysosomallysosomal
enzymesenzymes
Oxygen metabolitesOxygen metabolites
Nitric oxideNitric oxide
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Mast cell Blood vessel
Plasma enzyme cascade
Neutrophil polymorph
Macrophage
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Can you explain signs of acuteCan you explain signs of acute
inflammation?inflammation? RuborRubor (redness)(redness)
CalorCalor (heat)(heat)
DolorDolor (pain)(pain)
TumorTumor (swelling)(swelling) FunctioFunctio laesalaesa (loss of function)(loss of function)
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Outcomes of acute inflammationOutcomes of acute inflammation ResolutionResolution
Healing by organisation (scarring)Healing by organisation (scarring)
Progression to chronic inflammationProgression to chronic inflammation
DeathDeath
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Bacterialproducts
Mastcells
Plasma enzymecascades
Blood vessels Neutrophil polymorphs
vasodilatation
oedema
Neutrophil
polymorphs intissue