1.Acute Inflammation & SIRS

8/9/2019 1.Acute Inflammation & SIRS

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ACUTE INFLAMMATION

&SYSTEMIC INFLAMMATORYRESPONSE SYNDROME

Jeppri

PriandanaNivedita Yurnita


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OVERVIEW OFINFLAMMATION

INFLAMMATION Protective response intended to eliminate

the initial cause of cell injury as well as thenecrotic cells and tissues resulting from theoriginal insult.to heal and reconstitute the damagedtissue.Main components : Vascular Reaction an Cellular Res!onse"#acti$ate % 'e iators t(at are eri$e )ro' !las'a!roteins an $arious cells*


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Car inal si+ns : heat ( calor ), redness(ru%or ), and swelling ( tu'or ) due tothe vascular changes and cell recruitment.Pain ( olor ) and loss of function ( )unctio

laesa ) consequences of mediatorela oration and leu!ocyte"mediateddamage.

Se$eral t !es o) cells an 'olecules

!la i'!ortant roles in in,a''ation- #lood leu!ocytes and plasma proteins,$ells of vascular walls$ells and (%$M) of the surrounding connectivetissue



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T(e co'!onents o) acute an c(ronic in,a''atorres!onses an t(eir !rinci!al )unctions


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Ste!s o) t(e In,a''atorRes!onse

(&)'ecognition of the injurious agent

( )'ecruitment of leu!ocytes( )'emoval of the agent(*)'egulation (control) of the response(+)'esolution (repair)

Can %e Acute or Chronic



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Ma.or Co'!onents in AcuteIn,a''ation

&) 0lterations in vascular cali er 1 ( Vaso ilation* causing erythema and warmth

) %/travasation and deposition of plasma uid andproteins (edema) # Increased vascularpermeability)

) %migration of the leu!ocytes from themicrocirculation and their accumulation in the focusof injury ( Cellular recruitment and activation *-


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Vaso ilatation Transient arteriolar

vasoconstriction ollowed byvasodilation

2nduced y mediators (eg. 3istamines)

4armth and redness at thein ammatory site5pens microvascular eds2ncreased intravascularhydrostatic pressure causes anearly transudate (protein"poor6ltrate of plasma) into interstitium.


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3istamines, rady!inins,leu!otrienes cause an early, rief (&+9 min.), immediate transientresponse in the form of endothelialcell contraction that leads tointercellular gaps in postcapillaryvenules

$yto!ine mediators (8;


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Endothelial injury results in vascularlea!age y causing endothelial cellnecrosis and detachment. >evere injuriesmay cause immediate direct endothelialcell damage (necrosis, detachment)ma!ing them lea!y until they are repaired(immediate sustained response ), or may

cause delayed damage as in thermal or?7 injury.

0ccumulation of activated leu!ocytesalong the vessel wall may pile"up and

damage the endothelium throughactivation and release of to/ic o/ygenradicals and proteolytic en-ymes(leukocyte-dependent endothelial cell

injury ) ma!ing the vessel lea!y.


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$ertain mediators (7%@


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Cellular Recruit'ent an Acti$ation

eu!ocytes leave the vasculatureroutinely through the followingsequence of events:

Margination and rolling 0dhesion and transmigration$hemota/is and activation

8hey are then free to participate in:Phagocytosis and degranulation

eu!ocyte"induced tissue injury


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T ! C"M#$!% #R"C!&& "' $!( "C*T! MI+RATI",


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Chemota-is eu!ocytes follow chemical gradient

(chemotactic su stances) to site of injury#acterial products$omplement components ($+a)$yto!ines (chemo!ine family e-+ ., 2 "A)

8# * (00 meta olite)Produced in response to infections andtissue damage and during immunologicreactions

$eu.ocyte Activation >timuli for activation include micro es,

products of necrotic cells, and severalmediators


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$eu.ocyte Activation


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P1A2OCYTOSISConsists of three distinct butinterrelated steps :

/0Recognition and Attachment of

the particle to the ingestingleu!ocyte

10!ngul ment , with su sequentformation of a phagocytic vacuole

20 illing and degradation of theingested material


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'ecognition and 0ttachment"psonins

>peci6c surface receptors, which recogni-e eithercomponents of the micro es and dead cells, or host

proteins $oat micro es and target them for phagocytosis

(opsonization) examples : anti odies of the 2g@, rea!down

products of the complement protein $ , and collectins $orresponding receptors :


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Cilling and Degradation Production of micro icidal su stances ('5> E ysosomal %n-ymes) >timulates an oxidative burst :

o 5/ygen consumptiono @lycogenolysiso @lucose o/idationo Production of '5>

phagocyte oxidase o/idi-es ;0DP3 converts o/ygen to supero/ide ion >upero/ide converted hydrogen pero/ide(! " # "$ # $ " ! " ).


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ysosomes of neutrophils

(azurophilic granules ) containen-yme myelopero/idase (MP5) MP5 converts 3 5 to 35$l

(hypochlorous radical). Powerful o/idant andantimicro ial agent

0fter !xygen burst% 3 5 ro!en

down to water and ! " y catalase Dead microorganisms degraded

y lysosomal acid hydrolases


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P1A2OCYTOSIS OF A PARTICLE #e+- %acteria*


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eu!ocyte"induced

tissue injury Destructive en-ymes may entere/tracellular space in event of:9 regurgitation during feeding& premature degranulation

9


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AA META3OLITES AND T1EIR ROLES ININFLAMMATION


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More >peci6c Mediators Cyto.ines

9 Protein cell products that act as a message to othercells, telling them how to ehave.

9 %/. 2 "&, 8;hort"acting solu le free"radical gas with manyfunctions

9 Produced y endothelial cells, macrophages, causes: 7ascular smooth muscle rela/ation and

vasodilation Cills micro es in activated macrophages $ounteracts platelet adhesion, aggregation, and

degranulation


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4inin & Clottin+ Casca e


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$omplement >ystem $omponents $&"$F present in inactive

form9 0ctivated via classic ($&) or alternative

($ ) pathways to generate M0$ ($+ 9 $F)that punch holes in micro e mem ranes

9 2n acute in ammation 7asodilation, vascular permea ility, mast cell

degranulation ($ a, $+a)

eu!ocyte chemota/in, increases integrinavidity ($+a)

0s an opsonin, increases phagocytosis ($ ,$ i)


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Co'!le'ent S ste'


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De6nition

2nfection9 Presence of microorganisms in a normally

sterile site.

#acteremia9 $ultivata le acteria in the lood stream.

>epsis9 8he systemic response to infection.

2f associated with proven orclinically suspected infection, >2'> iscalled HsepsisI.

American College of Chest Physicians/Society of Critical Care Medicine ConsensusConference Committee. Crit Care Med. 1992;20 !"#$!%#.


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>2'>(>ystemic 2n ammatory 'esponse

>yndrome) 8he systemic response to a wide range of stresses.

9 8emperature J AK$ (& .*K) or L =K$ (F=.AK


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>evere >epsis

>epsis with organ hypoperfusionone of the followings :

9 >#P L F mm3g9 0cute mental status change9 Pa5 ( L = mm3g on '0 (Pa5 (


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'elationship etween >2'>and >epsis

&one 'C et al( Chest1992;101 1"#$)).


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8he >epsis $ontinuum

0 clinical response arisingfrom a nonspeci6c insult,with of the following:

8 J A o$ or L = o$3' JF eats min'' J min4#$ J& , mm orL*, mm or J& N

ands

SIRS = systemic inflammatoryresponse syndrome

S*'S +ith a ,resumed or confirmed

infectious ,rocess

Chest 1992;101 1"##.

SepsisSIRSSevereSepsis

SepticShock

Se,sis +ithorgan failure

'efractoryhy,otension


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Mortalit rate in SIRS

'angel$-rausto( et al. AMA 2% 11%$12 ( 199).


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;ormal >ystemic 'esponseto 2nfection and 2njury (&)

eu!ocytosis Mo ili-es neutrophils into thecirculation

8achycardia 2ncreases cardiac output, lood owto injuried tissue


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;ormal >ystemic 'esponseto 2nfection and 2njury ( )

0cute"Phase 'esponses9 0nti"infective

2ncreases synthesis of complement factors,micro e pattern"recognition molecules(mannose"

inding lectin, #P, $'P, $D&*, 5thers) >equesters iron (lactoferrin) and -inc

(metallothionein)

Mandell et al. Princi,als and Practice of *nfectious iseases"th ed;90" 90"$92".


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;ormal >ystemic 'esponseto 2nfection and 2njury ( )

0nti"in ammatory9 'eleases anti"in ammatory neuroendocrine

hormones (cortisol, 0$83, epinephrine, "M>3) 2ncreases synthesis of proteins that help

prevent in ammation within the systemiccompartment $yto!ine antagonists (2 "&'a, s8;


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Nor'al S ste'icRes!onse to In)ectionan In.ur #5* Procoagulant

9 4alls oS infection, prevents systemic spread 2ncreases synthesis or release of 6 rinogen, P02"&, $*

Decreases synthesis of protein $, anti"throm in 222 Meta olic

9 Preserves euglycemia, mo ili-es fatty acids, aminoacids

%pinephrine, cortisol, glucagon, cyto!ines 8hermoregulatory

9 2nhi its micro ial growth


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Ris/ )actors o) se!sis

aggressive oncological chemotherapy and radiation therapy use of corticosteroid and immunosuppressive therapies for

organ transplants and in ammatory diseases longer lives of patients predisposed to sepsis, the elderly, diabetics,

cancer patients, patients with major organ failure, and with granulocyopenia.

;eonates are more li!ely to develop sepsis (e/ . group #>treptococcal infections ).

increased use of invasive devices such as surgical protheses, inhalationequipment, and intravenous and urinary catheters.

indiscriminate use of antimicro ial drugs that createconditions of overgrowth, coloni-ation, and su sequentinfection y aggressive, antimicro ial"resistant organisms .

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1.Acute Inflammation & SIRS