Acute & Chronic Inflammation

Learning Objectives
At the end of the lecture, student should be able to; Define inflammation Describe the overview of Cellular Mechanisms Involved in Acute Inflammation Give Examples of Acute Inflammator !esponses Differentiate "etween Acute and Chronic Inflammation Give Examples of Chronic Inflammation

Inflammation- The Root Of All Disease?

Introduction/Definition

General eatures of Inflammation

Inflammator reactions are tri##ered b a variet of stimuli$ Infections %bacterial, viral, parasitic& and microbial toxins Trauma %blunt and penetratin#& !h"sical and chemical agents %thermal in'ur , e(#(, burns or frostbite; irradiation; some environmental chemicals& Tissue necrosis %from an cause& oreign bodies %splinters, dirt, sutures& Immune reactions %h persensitivit or autoimmunit &

Role Of Tissue And #ells In Inflammation

Role of tissue and cells in inflammation

The circulating cells are$
)eutrophils( Monoc tes( Eosinophils( * mphoc tes( "asophils( +latelets(

%igns & %"m'toms Of Inflammation

,hese are$ -ever %increase temperature&( +ain( ,issue dama#e( .wellin# of tissue( !edness of tissue( *oss of movements or restricted movement, if near 'oints(

The four cardinal signs of inflammation

Earl Gree/ and !oman ph sicians reco#ni0ed these si#ns as$ Dolor %pain& Calor %heat& !ubor %redness& ,umor %swellin#&

T"'es Of Inflammation
Inflammation is divided into I - Acute inflammation, which occurs over seconds, minutes, hours, and da s( II - #hronic inflammation, which occurs over lon#er times, da s 1 months(

Acute Inflammation
Acute inflammation( be#ins within seconds to minutes followin# the in'ur of tissues( ,he dama#e ma be purel ph sical, or it ma involve the activation of an immune response(

#hronic Inflammation
#hronic inflammation is of lon#er duration and is associated histolo#icall with the presence of$ * mphoc tes and macropha#es( ,he proliferation of blood vessels( -ibrosis and tissue necrosis(

Res'onse Of Inflammation
,he main processes are$

I - Increased blood flow( II - Increased permeabilit ( III - Mi#ration of neutrophils( I) - Chemotaxis( ) - *eucoc tes recruitment 1 activation(

Res'onse Of Inflammation
,he main processes are$ I - Increased blood flo* due to dilation of blood vessels %arterioles& suppl in# the re#ion( II - Increased 'ermeabilit" of the capillaries, allowin# fluid and blood proteins to move into the interstitial spaces

Res'onse Of Inflammation
III - +igration of neutro'hils %and perhaps a few
macropha#es& out of the venules and into interstitial spaces(

Res'onse Of Inflammation
I) - #hemota,is
2nce outside the blood vessel, a neutrophil is #uided towards an infection b various diffusin# chemotactic factors( Examples include the chemo-ines and the com'lement 'e'tide #.a, which is released when the complement s stem is activated either via specific immunit or innate immunit (

Res'onse Of Inflammation
) - Leucoc"tes recruitment & activation/
,his is the first step is the bindin# of the neutrophils to the endothelium of the blood vessels( ,he bindin# is due to molecules, called cell adhesion molecules 0#A+s1, found on the surfaces of neutrophils and on endothelial cells in in'ured tissue(

Res'onse of Inflammation
) - Leucoc"tes recruitment & activation 0contd/1 ,he bindin# of leu/oc tes occur in two steps$

 In the first ste', adhesion molecules called selectins ti#htl #ather the neutrophil to the endothelium, so that it be#ins rollin# alon# the surface(

Res'onse of Inflammation
) - Leucoc"tes recruitment & activation 0contd1/
In a second ste'( a much ti#hter bindin# occurs throu#h the interaction of I#A+s on the endothelial cells with integrins on the neutrophil(

Acute Inflammation 0recruitment of neutro'hils1

Res'onse of Inflammation
2osino'hils/
3owever, in some circumstances eosino'hils rather than neutrophils predominate in acute inflammation( ,his tends to occur with parasites %worms&, a#ainst which neutrophils have little success(

Res'onse of Acute Inflammation

Increased 3lood lo*( increased 'ermeabilit" and 2dema in Inflammation ,he increased blood flow 1 increased permeabilit are readil visible within a few minutes followin# a scratch that does not brea/ the s/in(

Res'onse of Acute Inflammation

At first, there is 'ale red line of scratch( *ater on there is accumulation of inflammator cells lead swellin#, 0inflammation1/ -inall , there is accumulation of interstitial fluid cause edema/

Acute Inflammation

Acute Inflammation

Acute Inflammation 0*ith 'us1

Acute Inflammation 0Acute 3ronchitis1

Acute Inflammation

#hronic inflammation
It is the inflammation of 'rolong duration %wee/s or months&( It is occurs as$ -ollowin# acute inflammation( 2ccurs, incidentall as active inflammation( 4ith tissue destruction(

4ith repair process(

#hronic Inflammation 0#hronic 3ronchitis1 #hronic Inflammation 0Tissue destruction-!ancreas1

#hronic Inflammation 0 ibrosis-'ancreas1

#auses of #hronic inflammation

I 5 +ersistent infection( II 5 +rolon#ed exposure to potentiall toxic a#ents( III 5 Autoimmunit (

#hronic 3ronchitis
#hronic Inflammation 0Lung1 #auses of #hronic inflammation

I - !ersistent infection$ "acteria( 6iruses( -un#i( +arasites

#hronic Gastritis

#hronic Inflammation

#auses of #hronic inflammation

II - !rolonged e,'osure to 'otentiall" to,ic agents$
Endo#enous, %atherosclerosis&( Exo#enous, % particulate silica5.ilicosis&(

#auses of #hronic inflammation

III - Autoimmunit"$ 2ccurs in$ !heumatoid arthritis( *upus er thmatosus(

#hronic Inflammation

0Rheumatoid arthritis1

#hronic inflammation
L"m'hoc"te( macro'hage( 'lasma cell 0mononuclear cell1 infiltration Tissue destruction b inflammator cells Attempts at re'air *ith fibrosis and angiogenesis %new vessel formation& 4hen acute phase cannot be resolved
7 7 7 +ersistent in'ur or infection %ulcer, ,"& +rolon#ed toxic a#ent exposure %silica& Autoimmune disease states %!A, .*E&

+or'hological eatures of #hronic Inflammation

,hese are characteri0ed b $ I 5 Infiltration b" mononuclear cells/ II - Tissue destruction/ III - Removal of damaged tissue( 0healing1/

+or'hological eatures of #hronic Inflammation

I - Infiltration b" mononuclear cells$ ,he mononuclear cells are become predominant after 45 hours( These include$ Macropha#es( * mphoc tes(

+lasma cells( Eosinophils( Mast cells(

+or'hological eatures of #hronic Inflammation

+acro'hages 7 .cattered all over %micro#lia, 8upffer cells, sinus histioc tes, alveolar macropha#es, etc( 7 Circulate as monoc tes and reach site of in'ur within 9: 7 :; hrs and transform 7 "ecome activated b , cell5derived c to/ines, endotoxins, and other products of inflammation

+or'hological eatures of #hronic Inflammation

T and 3 l"m'hoc"tes Anti#en5activated %via macropha#es and dendritic cells& !elease macropha#e5activatin# c to/ines %in turn, macropha#es release l mphoc te5activatin# c to/ines until inflammator stimulus is removed& !lasma cells ,erminall differentiated " cells %of l mphoc tes&( +roduce antibodies( 2osino'hils 7 -ound especiall at sites of parasitic infection, or at aller#ic %I#E5mediated& sites( 7 Eosinophils have hi#hl cationic proteins, which are toxic to parasites(

+or'hological eatures of #hronic Inflammation

II - Tissue destruction 2ccur due to$ Inflammator cells( +ersistent infectin# material( III - Removal of damaged tissue( 0healing1$ 2ccur b proliferation of small blood vessels, %an#io#enesis&( +roliferation of fibroblast, %fibrosis5repair&

Granulomatous Inflammation
Clusters of , cell5activated macropha#es, which en#ulf and surround indi#estible forei#n bodies %m cobacteria, H. capsulatum, silica, suture material& !esemble s<uamous cells, therefore called =e'ithelioid> #ranulomas with 'eri'heral l"m'hoc"tes( fibrosis & multinucleated giant cells/

#hronic Granulomatous Inflammation #hronic Granulomatous Inflammation #hronic Granulomatous Inflammation L"m'h 6odes and L"m'hatics

7 7 7

* mphatics drain tissues

-low increased in inflammation Anti#en to the l mph node ,oxins, infectious a#ents also to the node
* mphadenitis, l mphan#itis ?suall contained there, otherwise bacteremia ensues ,issue5resident macropha#es must then prevent overwhelmin# infection

%"stemic effects
ever 7 2ne of the easil reco#ni0ed c to/ine5mediated %esp( I*5@, I*5A, ,)-& acute-phase reactions includin# Anorexia ./eletal muscle protein de#radation 3 potension Leu-oc"tosis 7 Elevated white blood cell count

Differences between Acute and Chronic Inflammation.

Acute Duration 2nset .pecificit Inflammator cells 6ascular chan#es -luid exudation and edema Cardinal clinical si#ns %redness, heat, swellin#, pain& ,issue necrosis .hort %da s& Acute )onspecific )eutrophils, macropha#es Active vasodilation, increased permeabilit B B #hronic *on# %wee/s to months& Insidious .pecific %where immune response is activated& * mphoc tes, plasma cells, macropha#es, fibroblasts )ew vessel formation %#ranulation tissue& 7 7 B %on#oin#& 7 %?suall & B %.uppurative and necroti0in# inflammation& -ibrosis %colla#en deposition& 2perative host responses . stemic manifestations Chan#es in peripheral blood 7 +lasma factors$ complement, immuno#lobulins, properdin, etc; neutrophils, nonimmune pha#oc tosis -ever, often hi#h B Immune response, pha#oc tosis, repair

*ow7#rade fever, wei#ht loss, anemia )eutrophil leu/oc tosis; l mphoc tosis %in -re<uentl none; variable leu/oc te viral infections& chan#es, increased plasma immuno#lobulin

Thank you