Inflammation (Acute and Chronic)- Student

8/6/2019 Inflammation (Acute and Chronic)- Student

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Learning OutcomesLearning Outcomes

At the end of this lecture, students are ableAt the end of this lecture, students are ableto :to :

1.1. define and list the signs of inflammationdefine and list the signs of inflammation

2.2. explain the vascular and cellular events inexplain the vascular and cellular events inthe acute inflammation.the acute inflammation.

3.3. describe and differentiate in writtendescribe and differentiate in written

between acute and chronic inflammationbetween acute and chronic inflammation4.4. explain the mediators of inflammation.explain the mediators of inflammation.


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What is inflammation?What is inflammation?

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The local response of living mammalian tissuesto injury due to any agent.

Body defense reaction in order to eliminate orlimitthe spread of injurious agent as well as to

remove the consequent necrosed cells andtissues.


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Causes of inflammation;Causes of inflammation;

ii.. Physical agentPhysical agent e.g. mechanical trauma, radiatione.g. mechanical trauma, radiation

etc.etc.

ii.ii. Chemical agentChemical agent e.g. simple chemical poisons,e.g. simple chemical poisons,organic poisonsorganic poisons

iii.iii. InfectiveInfective agentsagents e.g. bacteria, viruses, parasites,e.g. bacteria, viruses, parasites,

their toxinstheir toxins

iv.iv. ImmunologicalImmunological agentsagents e.g. Age.g. Ag--AbAb reaction, cellreaction, cell

mediatedmediated

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Inflammatory response has many players include;Inflammatory response has many players include;

ii.. Circulating cells & plasma proteinsCirculating cells & plasma proteins

ii.ii.Vascular wall cellsVascular wall cells

iii.iii. Cells & extracellular matrix of the surroundingCells & extracellular matrix of the surrounding

connective tissueconnective tissue

Earliest reactions of inflammatory response occursEarliest reactions of inflammatory response occurs

ininVASCULAR CONNECTIVE TISSUEVASCULAR CONNECTIVE TISSUE..

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Stages Of InflammationStages Of Inflammation

INFLAMMATION

ACUTEINFLAMMATION

CHRONICINFLAMMATION

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Acute inflammationAcute inflammation

Short duration & represents the early bodyShort duration & represents the early bodyreaction and usually followed by repairreaction and usually followed by repair

The main features :The main features :

(a)(a) Accumulation of Accumulation offluidfluid && plasmaplasma at theat the

affected siteaffected site

(b)(b) Intravascular activationIntravascular activation of plateletsof platelets

(c)(c) PolymorphonuclearPolymorphonuclear neutrophilsneutrophils asas

inflammatory cellsinflammatory cells

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Chronic InflammationChronic Inflammation

-- longerlonger durationduration andand occursoccurs eithereither ::(a)(a) afterafter thethe causativecausative agentagent ofof acuteacuteinflammationinflammation persistspersists forfor aa longlongtimetime

(b)(b) Stimulus that induces chronicStimulus that induces chronicinflammation from the beginninginflammation from the beginning

-- main features :main features :

presencepresence ofof chronicchronic inflammatoryinflammatory cellscells((lymphocyteslymphocytes,, plasmaplasma cellscells andandmacrophagesmacrophages))


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Signs ofInflammationSigns ofInflammation

The famous 4The famous 4 cardinal signscardinal signs of acuteof acuteinflammation:inflammation:

((ii)) ruborrubor (redness)(redness)(ii)(ii) tumortumor (swelling)(swelling)

(iii)(iii) calorcalor (heat)(heat)

(iv)(iv) dolordolor (pain)(pain)Added latestAdded latest functiofunctio laesalaesa (loss of(loss of

function)function)

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Heat Redness Swelling Pain Loss Of Func.

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((ii)) VASCULAR EVENTSVASCULAR EVENTS

Alteration in the microvasculatureAlteration in the microvasculature(arterioles, capillaries &(arterioles, capillaries & venulesvenules))

Earliest response to tissue injuryEarliest response to tissue injuryAlterations includes:Alterations includes:

(a)(a)haemodynamichaemodynamic changeschanges

(b)(b)changes in vascular permeabilitychanges in vascular permeability

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(a)(a) HaemodynamicHaemodynamic ChangesChanges

Earliest featuresEarliest features ofofinflammatory responseinflammatory responseresult from changes in theresult from changes in the vascular flowvascular flow

andand calibrecalibre of small blood vessels in theof small blood vessels in theinjured tissueinjured tissue

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The sequence of these changes:The sequence of these changes:

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Transient vasoconstriction

Persistent progressive vasodilatation

Local hydrostatic pressure

Slowing or stasis

Leucocytic margination


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LewisLewis Triple Response/ red lineTriple Response/ red line

responseresponse Appears a few second; Capillary & venules

dilatationRed line

Bright reddish appearance appearance/flush surrounding

the red line; Arteriolar dilationFlare

Swelling or oedema of thesurrounding skin occurring dueto transudation of fluid into theextravascular space

wheal

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Triple response


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(b) Altered vascular(b) Altered vascular

permeabilitypermeability Vascular changes begin quickly after the injuryVascular changes begin quickly after the injurybut may develop atbut may develop atvariables ratesvariables rates, depending on, depending on

thethe nature & severity of the original injury.nature & severity of the original injury.

The interchange of fluid between the vascular &The interchange of fluid between the vascular &

extra vascular space results from balance of fluidextra vascular space results from balance of fluid

into the vascular space or out into the tissuesinto the vascular space or out into the tissuesdepend on 4 different types of pressure.depend on 4 different types of pressure.

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Changes vascular permeabilityChanges vascular permeability

Hydrostatic

pressure ?

Oncotic

pressure ?

Osmoticpressure ?

Lymphflow ?

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Fluid interchange between blood andFluid interchange between blood and

extracellular fluid (ECF). (HP = Hydrostaticextracellular fluid (ECF). (HP = Hydrostatic

pressure, OP = Osmotic pressure)pressure, OP = Osmotic pressure)

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NOOEDEMA OEDEMA


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MECHANISMS OFINCREASED VASCULARMECHANISMS OFINCREASED VASCULAR

PERMEABILI

TYPERMEABILI

TY

(i)(i) Endothelial cell contractionEndothelial cell contraction

(ii)(ii) Endothelial cell retractionEndothelial cell retraction(iii)(iii) Direct injury to endothelial cellsDirect injury to endothelial cells

(iv)(iv) Endothelial injury mediated by leucocytesEndothelial injury mediated by leucocytes

(v)(v) NeovascularisationNeovascularisation

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ii) CELLULAR EVENTSii) CELLULAR EVENTS

CellularCellular eventsevents;; cellscells ofof thethe acuteacute inflammatoryinflammatoryresponseresponse areare thethe neutrophilsneutrophils,, monocytesmonocytes &&

macrophagesmacrophages..

PolymorphonuclearPolymorphonuclear neutrophilsneutrophils (PMNs)(PMNs)

(within 24 hrs; Life long 24(within 24 hrs; Life long 24--48 hrs)48 hrs)

MonocytesMonocytesMacrophagesMacrophages

(24(24--48 hrs; Survive much longer)48 hrs; Survive much longer)

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TheThe movementsmovements ofof neutrophilsneutrophils outout ofof thethe

vesselsvessels && theirtheir rolerole inin combatcombat cancan bebedivideddivided intointo 55 stepssteps;;

ii.. MarginationMargination ??

ii.ii.AdhesionAdhesion ??

iii.iii. Emigration/Emigration/ diapedesisdiapedesis ??

iv.iv. ChemotaxisChemotaxis ??

v.v. PhagocytosisPhagocytosis && degranulationdegranulation ??

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THE INFLAMMATION PROCESSTHE INFLAMMATION PROCESS

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Neutrophil MarginationNeutrophil Margination

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FATE OF ACUTE INFLAMMATIONFATE OF ACUTE INFLAMMATION

Acute inflammation generally has one ofAcute inflammation generally has one of

FOUR (4) outcomes;FOUR (4) outcomes;

ii.. ResolutionResolution complete return to normal/complete return to normal/

tissue changes are slight and cellular changestissue changes are slight and cellular changesare reversibleare reversible egeg; resolution in lobar; resolution in lobar

pneumoniapneumonia

ii.ii. Healing byHealing by scarrimgscarrimg tissue destruction istissue destruction isextensive, no tissue regeneration; healing byextensive, no tissue regeneration; healing by

fibrosisfibrosis

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iii)iii) SuppurationSuppuration the progression process ofthe progression process of

severe necrosis cause bysevere necrosis cause by pyogenicpyogenic bacteria;bacteria;

neutrophilicneutrophilic infiltration; form aninfiltration; form an abcessabcess;;

abcessabcess organisedorganised by dense fibrous tissueby dense fibrous tissue

and get calcifiedand get calcified

iv)iv) Progression to chronic inflammation mayProgression to chronic inflammation may

follow acute inflammationfollow acute inflammation, although signs, although signsof chronic inflammation may be present atof chronic inflammation may be present at

the onset of injury; healing proceed side bythe onset of injury; healing proceed side byside.side.

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AssessmentAssessment

What is giant cell?What is giant cell?

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ChronicChronic inflammationinflammation;;

prolongedprolonged processprocess inin whichwhich tissuetissuedestructiondestruction andand inflammationinflammation occuroccuratat thethe samesame timetime..

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II) CHRONIC INFLAMMATIONII) CHRONIC INFLAMMATION


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CausedCaused oneone ofof thethe followingfollowing 33 waysways::

ii)) ChronicChronic inflammationinflammation followingfollowing acuteacute

inflammationinflammation thethe tissuetissue destructiondestruction isisextensiveextensive,, oror bacteriabacteria survivesurvive && persistpersist inin

smallsmall numbersnumbers atat thethe sitesite ofof acuteacute inflammationinflammation

ii)ii) RecurrentRecurrent attacksattacks ofof acuteacute inflammationinflammation

repeatedrepeated boutsbouts ofof acuteacute inflammationinflammation egeg;;

repeatedrepeated acuteacute infectioninfection ofof gallbladdergallbladder

chronicchronic cholecystitischolecystitis

iii)iii) StartingStarting dede novonovo infectioninfection withwith organismsorganisms of oflowlow pathogenecitypathogenecity (chronic(chronic fromfrom thethe beginningbeginning))

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GeneralGeneral featuresfeatures ofof ChronicChronic inflammationinflammation::

ii.. InfiltrationInfiltration withwith mononuclearmononuclear cellscells

InfiltratedInfiltrated byby mononuclearmononuclear inflammatoryinflammatory cellscells ::phagocytesphagocytes && lymphoidlymphoid cellscells

phagocytesphagocytes :: circulatingcirculating monocytesmonocytes,, tissuetissue

macrophages,macrophages, epithelioidepithelioid cells,cells, multinucleatedmultinucleated

giantsgiants cellscells

iiii.. TissueTissue destructiondestruction

CentralCentral featurefeature ofof lesionslesions

iiiiii.. ProliferativeProliferative changeschanges

ResultResult ofof necrosis,necrosis, proliferationproliferation ofof smallsmall vesselsvessels

andand fibroblastsfibroblasts;; healinghealing byby fibrosisfibrosis andand collagencollagen

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Types of chronic inflammationTypes of chronic inflammation

NONNON--SPECIFICSPECIFIC

Formation of granulationFormation of granulationtissue and healing bytissue and healing by

fibrosisfibrosis EgEg; Chronic; Chronic osteomyelitisosteomyelitis,,

Chronic ulcerChronic ulcer

SPECIFICSPECIFIC

Injurious agent causes aInjurious agent causes acharacteristiccharacteristic histologichistologic

tissue responsetissue response EgEg; tuberculosis, leprosy,; tuberculosis, leprosy,

syphilissyphilis

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Types of chronic inflammationTypes of chronic inflammation(based on histological classification)(based on histological classification)CHRONIC NONCHRONIC NON--SPECIFICSPECIFIC

INFLAMMATIONINFLAMMATION

CharacterisedCharacterised by:by:

(a) non(a) non--specificspecific

inflammatory cellinflammatory cellinfiltrationinfiltration egeg; chronic; chronicosteomyelitisosteomyelitis, lung, lung abcessabcess

(b) Infiltration by(b) Infiltration by

polymorphs andpolymorphs and abcessabcessformationformation EgEg;;ActinomycosisActinomycosis

CHRONIC GRANULOMATOUSCHRONIC GRANULOMATOUSINFLAMMATIONINFLAMMATION

Formation ofFormation of granulomasgranulomas

EgEg; tuberculosis, leprosy,; tuberculosis, leprosy,

syphilis,syphilis, sarcoidosissarcoidosis

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GranulomatousGranulomatous InflammationInflammation

GranulomatousGranulomatous inflammation; mechanism whereby theinflammation; mechanism whereby the

body deals with certainbody deals with certain indigestibleindigestiblebacteria, fungi, orbacteria, fungi, or

foreign particles.foreign particles.

Examples;Examples;ii.. BacteriaBacteria e.g. Tuberculosis, Leprosye.g. Tuberculosis, Leprosy

ii.ii. ParasiticParasitic e.g.e.g. SchistosomiasisSchistosomiasis

iii.iii. FungaFungal e.g.l e.g. HistoplasmaHistoplasma capsulatumcapsulatum

iv.iv. Inorganic metalsInorganic metals oror dustsdusts e.g. Silicosise.g. Silicosis

v.v. Foreign bodyForeign bodye.g. Vascular grafte.g. Vascular graft

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INJURY(e.g; by M. tuberculosis, talc

Failure to digest agent

Weak acute inflammatory response

Persistence of injurious agent

T cell-mediated immune response Poorly digestible agent

Activation of CD+4 T cells (release oflymphokines IL-1, IL-2. growth factors

IFN- and IFN-)

Monocyte chemotactic factor


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Accumulation of tissue macrophages(Increased recruitment from circulation, local proliferation)

Macrophages activated by IFN-

Transformed to epithelioid cells, giant cells

GRANULOMA


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Granuloma tissueGranuloma tissue

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What is Mediator ???What is Mediator ???

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Mediators Of InflammationMediators Of Inflammation

What are mediators?What are mediators?

ii.. May be circulating in the plasma or may be producedMay be circulating in the plasma or may be produced

locally by cells at the site of inflammation.locally by cells at the site of inflammation.

ii.ii. Induce their effects by binding to specific reactors onInduce their effects by binding to specific reactors on

target cells.target cells.

iii.iii. May stimulate target cells to release secondaryMay stimulate target cells to release secondary effectoreffector

molecules.molecules.iv.iv. May act on only one or a very few targets.May act on only one or a very few targets.

v.v. Function is generallyFunction is generally tighlytighly regulated.regulated.

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2 types of chemical mediators of Acute inflammation;2 types of chemical mediators of Acute inflammation;

i.i. PlasmaPlasma--derived mediatorsderived mediators e.g. kinin system,e.g. kinin system,

coagulation & fibrinolytic system, complementcoagulation & fibrinolytic system, complementsystem.system.

ii.ii. CellCell--derived mediatorsderived mediators e.g. vasoactive amines,e.g. vasoactive amines,

cytokines, platelet activating factor, growth factor.cytokines, platelet activating factor, growth factor.

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Inflammatory cells release mediators such as;Inflammatory cells release mediators such as;

ii.. CytokinesCytokines--((ILIL--8, interferon8, interferon--neutrophilneutrophil))

ii.ii.VasoactiveVasoactive aminesamines--

((histamine,histamine, serotininserotinin-- mast cell,mast cell, basophilbasophil, platelet, platelet))iii.iii. ProstanoidsProstanoids--

((arachidonicarachidonic acidacid metabolicsmetabolics))

iv.iv. Reactive oxygen intermediatesReactive oxygen intermediates--

((released from activatedreleased from activated neutrophilneutrophil))

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If the mediators in the inflammatory response areIf the mediators in the inflammatory response are

successful;successful;

i.i. Invading & infectious agents will be removed.Invading & infectious agents will be removed.

ii.ii. Damaged tissues will be disposed of.Damaged tissues will be disposed of.

iii.iii. New tissue will be induced to form.New tissue will be induced to form.

iv.iv. New blood supply to the area will be established.New blood supply to the area will be established.

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Chronic inflammation cellsChronic inflammation cells

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Chronic InflammationChronic Inflammation Lung AbscessLung Abscess4747


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Morphologic Patterns Of Acute & ChronicMorphologic Patterns Of Acute & Chronic

InflammationInflammation

Serous inflammationSerous inflammation; excessive clear watery; excessive clear watery

fluid with a variable protein content but nofluid with a variable protein content but nofibrin e.g. pleural effusion associated withfibrin e.g. pleural effusion associated with

tuberculosis.tuberculosis.

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Serous InflammationSerous Inflammation -- effusioneffusion

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Serous InflammationSerous Inflammation -- effusioneffusion5050


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Fibrinous inflammationFibrinous inflammation; the formation of; the formation offibrin is striking e.g. in acute pleurisy.fibrin is striking e.g. in acute pleurisy.

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Fibrinous InflammationFibrinous Inflammation5252


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Purulent (Suppurative) inflammationPurulent (Suppurative) inflammation;;production of pus is the main characteristicproduction of pus is the main characteristic

e.g. abscess & acute apendicitis.e.g. abscess & acute apendicitis.

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Purulent InflammationPurulent Inflammation -- PUSPUS

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Purulent InflammationPurulent Inflammation -- PUSPUS

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Ulceration;Ulceration; complicationcomplication of many diseaseof many disease

processprocess

Divided into 2 groups;Divided into 2 groups;i.i. Simple ulcerSimple ulcer

ii.ii. Malignant (cancerous) ulcerMalignant (cancerous) ulcer

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A skin ulcer resulting from infection withA skin ulcer resulting from infection withCorynebacterium diphtheriaeCorynebacterium diphtheriae

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Mouth Apthus UlcerMouth Apthus Ulcer

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Gastric UlcerGastric Ulcer

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"Each time you are honest and conduct

yourself with honesty, a success force will

drive you toward greater success. Eachtime you lie, even with a little white lie,

there are strong forces pushing you towardfailure."

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THANKYOUTHANKYOU

FOR YOURATTENTIONFOR YOURATTENTION

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Inflammation (Acute and Chronic)- Student