8 Acute Inflammation IW

8/3/2019 8 Acute Inflammation IW

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Acute InflammationAcute Inflammation



Inflammation & HealingInflammation & Healing Recognition of injuryRecognition of injury

Removal of injurious stimulusRemoval of injurious stimulus

Repair of any damageRepair of any damage



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



Cell Injury

Acute Inflammation

Chronic Inflammation

Healing & Repair





Acute inflammationAcute inflammation

Stereotyped responseStereotyped response

Delivers molecules and cells to site of Delivers molecules and cells to site of injuryinjury



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





Acute myocardial infarction



Vascular changesVascular changes

Vasodilatation & increased blood flowVasodilatation & increased blood flow

Increased vascular permeabilityIncreased vascular permeability



Vascular permeabilityVascular permeability Endothelial cell contractionEndothelial cell contraction

Direct injuryDirect injury

Leukocyte dependent injuryLeukocyte dependent injury

IncreasedIncreased transcytosistranscytosis VascularVascular neogenesisneogenesis



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



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





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



ChemotacticChemotactic AgentsAgents NN--formylformyl––methioninemethionine peptides frompeptides from

bacteriabacteria C5aC5a

LeukotrieneLeukotriene BB44

ILIL--88



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



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



Chemical Mediators ControlChemical Mediators Control

InflammationInflammation

Cell derivedCell derived –– endogenous and newlyendogenous and newlysynthesisedsynthesised

Plasma derivedPlasma derived



Cell derivedCell derived – – endogenousendogenous

(pre(pre--formed)formed)

Histamine (vasodilator, increasesHistamine (vasodilator, increasesvascular permeability)vascular permeability)–– mast cellsmast cells

SerotoninSerotonin –– plateletsplatelets

LysosomalLysosomal enzymesenzymes –– neutrophilsneutrophils



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





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)



Plasma enzyme cascadesPlasma enzyme cascades

preformed in bloodpreformed in blood

ClottingClotting

FibrinolysisFibrinolysis

ComplementComplement

KininKinin



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



XIIa

Coagulation:fibrinopeptides

Kinin system:

Bradykinin

Fibrinolysis:Fibrin degradation products

Complement:

C3a, C5a, MAC

kallikrein

plasmin thrombin



VasodilatationVasodilatation ProstaglandinsProstaglandins

Nitric oxideNitric oxide

HistamineHistamine



Increased vascular permeabilityIncreased vascular permeability Histamine & serotoninHistamine & serotonin

C3a & C5aC3a & C5a

BradykininBradykinin

LTCLTC44, LTD, LTD44, LTE, LTE44

PAFPAF



ChemotaxisChemotaxis C5aC5a

LTBLTB44

ILIL--1, TNF1, TNF



FeverFever ILIL--11

TNFTNF

ProstaglandinsProstaglandins



PainPain ProstaglandinsProstaglandins

BradykininBradykinin



Tissue damageTissue damage NeutrophilNeutrophil & macrophage& macrophage lysosomallysosomal

enzymesenzymes

Oxygen metabolitesOxygen metabolites

Nitric oxideNitric oxide



Mast cell Blood vessel

Plasma enzyme cascade

Neutrophil polymorph

Macrophage



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)



Outcomes of acute inflammationOutcomes of acute inflammation ResolutionResolution

Healing by organisation (scarring)Healing by organisation (scarring)

Progression to chronic inflammationProgression to chronic inflammation

DeathDeath



Bacterialproducts

Mastcells

Plasma enzymecascades

Blood vessels Neutrophil polymorphs

vasodilatation

oedema

Neutrophil

polymorphs intissue

Documents

8 Acute Inflammation IW