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AcuteInflammation

JonathanFox jfox7@uwyo.edu

Whatisacuteinflammation? Whatisinflammation?Alocalized, regionalor systemicresponseofthebodytoforeignmaterial, perceivedforeignmaterial,ordamagedhosttissue. Itcomprisesspecificinflammatorycellsandsoluble inflammatorymediatorsthataredirectedat i fl t di t th t di t d t destroyingandremovingtheincitingcause. Whatdoesacutemean?Sudden onsetand/orhaving hadashortduration(1 ~37days)

Eyelidabscess

Dermatitis

Goatmastitis

Bovineliverabscesses Contactdermatitis

Brainabscess

Frostnip

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Whatisthepurposeofacute inflammation?
Isolatessourceofinfectione.g.abscess Destroysdiseasecausingmicroorganisms [viruses,bacteriaandfungi]andparasites [protozoaandmetazoa] Early degradation of dead tissue e g myocardial Earlydegradationofdeadtissuee.g.myocardial infarct
Intheprocessofdestroyingmicroorganismsand parasitesacuteinflammationhasdamagingeffects ontissuesandorgans Localtissue damageisoftenthecostrequiredto preventlifethreateningsystemicinfections

Relationshipbetweenacuteandchronicinflammation
Maybelifethreateninge.g.brainabscess LocalizedSystemicLifethreatening

Noresidual damage Residualtissue damage[scar] damage [scar]

Acuteinflammation [1 7days] [17 days]

Chronicinflammation

Chronicinflammation
Cleanupphase,severaldaysto Clean up phase several days to months

Persistentchronic inflammation

LocalizedSystemicLifethreatening

MANYSCENARIOSOFDISEASEPROGRESSIONAND/ORRESOLUTION DEPENDS ONMANYFACTORSINCLUDINGPATHOGEN,HOSTANDTREATMENTRELATED VARIABLES

Acuteinflammationcanbeapathologic ratherthanprotectiveprocess
Aberrantactivationoftheacuteinflammatory responsecandamagevarioustissuesandorgans withouthavinganybenefits Manydiseaseexamples
Asthma Lupus[systemiclupuserythrematosus] Fleaallergyindogs Immunemediatedhemolyticanemia

Thiswillbecoveredinthelectureonimmune mediateddiseases[autoimmunityand hypersensitivity]

THESETOPICSWILLBECOVEREDINALATERLECTURE

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Whatarethesymptomsandsignsof acuteinflammation?

Whatarethesymptomsandsignsof acuteinflammation?
Rubor Tumor Dulor Calor Functio laesa

Celsus(ca30BC38AD)

Galen(AD129 199/217)

MechanismsofAcuteInflammation.I
Overview Initiationofacuteinflammation Vascularresponse Cellularresponse Cellular response Destructionofmicroorganisms Involvementoflymphatics andlymphnodesin inflammation Systemiceffectsofinflammation

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OverviewofAcuteInflammation
Initiation

Vasodilation rubor,calor

Leakageofproteins Leakage of proteins tumor

Emigrationofneutrophils

Destructionofforeignmaterial

Resolution

Initiationofacuteinflammation.I.
Hughdiversityofstimulantsofacuteinflammation
Infectious[viruses,bacteria,fungi,parasites] Noninfectioustissuedamage/death
Burn,frostbite,hypoxicdamage,foreignbodies,trauma Many factors released from dead tissue promote inflammation Manyfactorsreleasedfromdeadtissuepromoteinflammation

Manysensingmechanismsforacuteinflammatory stimulants
Complementsystem* Tolllikereceptors Antibodies*
*Coveredinmoredetailinthisandsubsequentlectures

Vascularresponse.I.
Vasodilation andincreasedvascularpermeability

Inflammatoryexudates keypoints Supplyfactorskeytomediatinginflammation Richinproteinse.g.immunoglobulins,complement Richincellse.g.neutrophils Exudatesonsurfaceorinsubstanceoftissue/organ

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Vascularresponse.II.
Mechanismsofincreasedvascular permeability
Mastcellreleasehistamine seelaterlecture. NOisagasreleasedbyvariouscelltypese.g. endothelialcellsandmacrophages.

Also,endotheliotropic infectiousagents Also endotheliotropic infectious agents

TypeIIIhypersensitivity seelaterlecture.

Cellularresponse.I.Neutrophils.
Derivedfrombone marrowprecursorcells (myeloblasts) Samelineageas eosinophils and and basophils Destructionofbone marrow(manycauses) willdepleteneutrophils inblood[neutropenia] andpredisposetowards infectiousdisease

Cellularresponse.II.Neutrophil migration.

KEYROLEOFVARIOUSINDUCEDCELLADHESIONMOLECULES ONENDOTHELIALCELLS,NEUTROPHILSANDEXTRACELLULAR MATRIXWITHINTISSUE

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Cellularresponse.III. Neutrophil structureandfunction.

NEUTROPHILGRANULESCONTAINALARGENUMBEROF PROTEINSREQUIREDTOMEDIATEINFLAMMATIONAND PROMOTEPATHOGENKILLING Tissuemigration:collagenase,elastase,laminin receptors Pathogenkilling:myeloperoxidase Pathogendegradation/digestion:lysosomal hydrolases

CellResponse.IV.
Bindingtopathogenandphagocytosis
Opsonization andphagocytosis CriticalroleofIgG and complementproteins Criticalroleofneutrophil receptorsforIgG and receptors for IgG and complementcomponents Fc receptor CR1 Criticalroleofsignaling pathwaystostimulate phagocytosis oncereceptor bindingoccurs

CellResponse.V.Oxygenradicalsand
microorganismkilling roleof myeloperoxidase andNADPHoxidase.
Myeloperoxidase (MPO) H202 + 2Cl +2Cl 2HOCl+2e 2HOCl + 2e
Myeloperoxidase contains heme group explains yellowgreenpus

NADPHoxidase
NADPHoxidase

O2 +NADPH O2 +2H+ +Fe2+

O2 +NADP+ Fe3+ +OH +OH.

Destructionof bacteriaetcby oxygenradicals

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CellResponse.VI.Destructionof pathogen,tissueandexudation
Drainingofpusontosurfaceofsiteofinflammation

Focalaccumulationofpusintissuecavities=abscessation

Liverabscessation

Roleoflymphatics ininflammation.I.
Tissueexudate drainsintolymphatics andenters regionalnodes Activateslocalimmuneresponseinnode(humoral andcellmediatedcomponents).Lymphoid hyperplasiaand/orinflammation(lymphadenitis)

Providesfutureimmunityforspecificagent.

Systemiceffectsofacuteinflammation
Leukocytosis increaseinwhitecellsinblood
Increasedbonemarrowrelease Increasedbonemarrowproliferation

Acutephaseproteins
C reactive protein serum amyloid A fibrinogen Creactiveprotein,serumamyloid A,fibrinogen Levelsincreaseinblood,liverderivedproteins

Fever
Helpsinflammatoryprocess,canbeharmful Pyrogens bacterialproducts,Interleukin1,Tumor necrosisfactoralpha Roleofhypothalamus

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Classificationofacuteinflammationsuggests underlyingcausesinspeciesspecificmanner
NecrotizingenteritismaysuggestSalmonellainsome speciese.g.human PurulentlymphadenitismaysuggestsStreptococcal infectioninsomespeciese.g.horses i f i i i h SerousarthritismaysuggestMycoplasma insome speciese.g.pigs

Summary consequencesofacute inflammation

Efficacyofinflammatoryand immuneresponse

LocalacuteinflammationSystemicinflammation(e.g.septicemia) TREATMENT

Death

Completeresolution noscar

Resolution withscar

Persistentchronic inflammation

Exampleexaminationquestions
Statefivesignsofacuteinflammation
Forthreeofthesestatebrieflyhowtheyoccur

Howdoneutrophils killbacteria? Whatisanabscess? Statethreefactorsthatwilldetermine whetheralocalizedinfectionbecomes systemicandcauselifethreateningdisease