Inflammation and wound healing. Pathophysiology

Inflammation and healing.
B.Pharm 2nd Sem Pathophysiology as per PCI.

1. Inflammation and Healing
Prepared by: Mrs. Deeksha gupta
Assistant Professor,
Krishna Institute of Pharmacy & Sciences, Kanpur

2. DEFINITION AND CAUSES:
Inflammationisdefinedasthelocalresponseoflivingmammaliantissuestoinjuryduetoanyagent.Itisa
bodydefensereactioninordertoeliminateorlimitthespreadofinjuriousagent,followedbyremovalofthe
necrosedcellsandtissues.Theagentscausinginflammationmaybeasunder:
1.Infectiveagentslikebacteria,virusesandtheirtoxins,fungi,parasites.
2.Immunologicalagentslikecell-mediatedandantigen-antibodyreactions.
3.Physicalagentslikeheat,cold,radiation,mechanicaltrauma.
4.Chemicalagentslikeorganicandinorganicpoisons.
5.Inertmaterialssuchasforeignbodies
SIGNSOFINFLAMMATION
TheRomanwriterCelsusin1stcenturyA.D.namedthefamous4cardinalsignsofinflammationas:
rubor(redness);
tumor(swelling);
calor(heat);and
dolor(pain).
Tothese,fifthsignfunctiolaesa(lossoffunction)waslateraddedbyVirchow.

3. TYPES OF INFLAMMATION

4. Continued…..
A.Acuteinflammationisofshortduration(lastinglessthan2weeks)andrepresentstheearlybodyreaction,
resolvesquicklyandisusuallyfollowedbyhealing.
Themainfeaturesofacuteinflammationare:
1.accumulationoffluidandplasmaattheaffectedsite;
2.intravascularactivationofplatelets;and
3.polymorphonuclearneutrophilsasinflammatorycells.
Sometimes,theacuteinflammatoryresponsemaybequitesevereandistermedasfulminantacute
inflammation.
B.Chronicinflammationisoflongerdurationandoccurseitherafterthecausativeagentofacute
inflammationpersistsforalongtime,orthestimulusissuchthatitinduceschronicinflammationfromthe
beginning.

5. MECHANISM OF INFLAMMATION
Acuteinflammatoryresponsebythehosttoanyagentisacontinuousprocessbutforthepurposeof
discussion,itcanbedividedintofollowingtwoevents:
I.Vascularevents.
II.Cellularevents.
Intimatelylinkedtothesetwoprocessesisthereleaseofmediatorsofacuteinflammation,discussed
justthereafter.
I.VASCULAREVENTS
Alterationinthemicrovasculature(arterioles,capillariesandvenules)istheearliestresponseto
tissueinjury.
Thesealterationsinclude:haemodynamicchangesandchangesinvascularpermeability.
Inandaroundtheinflamedtissue,thereisaccumulationofoedemafluidintheinterstitial
compartmentwhichcomesfrombloodplasmabyitsescapethroughtheendothelialwallof
peripheralvascularbed.
Intheinitialstage,theescapeoffluidisduetovasodilatationandconsequentelevationin
hydrostaticpressure.
Thisistransudateinnature.
Butsubsequently,thecharacteristicinflammatoryoedema,exudate,appearsbyincreasedvascular
permeabilityofmicrocirculation.

6. Continued…..
II. CELLULAR EVENTS
Thecellularphaseofinflammationconsistsof2processes:
1.exudationofleucocytes;and
2.phagocytosis.
1. Exudation of Leucocytes
Theescapeofleucocytesfromthelumenofmicrovasculaturetotheinterstitialtissueisthemostimportant
featureofinflammatoryresponse.Inacuteinflammation,polymorphonuclearneutrophils(PMNs)comprisethe
firstlineofbodydefense,followedlaterbymonocytesandmacrophages.
Fig.Sequenceofchangesintheexudationofleucocytes.A,Normalaxialflowofbloodwithcentralcolumnofcellsandperipheralzoneofcell-freeplasma.B,Marginationandpavementofneutrophils
withnarrowplasmaticzone.C,Adhesionofneutrophilstoendothelialcellswithpseudopodsintheintercellularjunctions.D,Emigrationofneutrophilsanddiapedesiswithdamagedbasement
membrane.

7. Continued…..
Phagocytosis
Phagocytosisisdefinedastheprocessofengulfmentofsolidparticulatematerialbythecells(cell-eating).Thecells
performingthisfunctionarecalledphagocytes.Thereare2maintypesofphagocyticcells:
i)Polymorphonuclearneutrophils(PMNs)whichappearearlyinacuteinflammatoryresponse,sometimescalledas
microphages.
ii)Circulatingmonocytesandfixedtissuemononuclearphagocytes,commonlycalledasmacrophages.
Neutrophilsandmacrophagesonreachingthetissuespacesproduceseveralproteolyticenzymeslikelysozyme,
protease,collagenase,elastase,lipase,proteinase,gelatinase,andacidhydrolases.Theseenzymesdegradecollagenand
extracellularmatrix.Themicrobeundergoestheprocessofphagocytosisbypolymorphsandmacrophagesandinvolves
thefollowing3steps:-
1.Recognitionandattachment
2.Engulfment
3.Killinganddegradation
Fig: Stages in phagocytosis of a foreign particle. A, Opsonization of the particle. B, Pseudopod engulfing the opsonized particle.
C, Incorporation within the cell (phagocytic vacuole) and degranulation. D, Phagolysosome formation after fusion of lysosome of the cell.

8. CHEMICAL MEDIATORS OF INFLAMMATION
Thesubstancesactingaschemicalmediatorsofinflammationmaybereleasedfromthecells,the
plasma,ordamagedtissueitself.Theyarebroadlyclassifiedinto2groups:
i)mediatorsreleasedbycells;and
ii)mediatorsoriginatingfromplasma.
Fig:- Chemical mediators of inflammation.

9. WOUND HEALING
Healing of skin wounds provides a classical example of combination of regeneration and repair described above.
Wound healing can be accomplished in one of the following two ways:
Healing by first intention (primary union)
Healing by second intention (secondary union).
Basic principles of wound healing:
Hemostasis: The process of wound healing begins with hemostasis, which is the immediate response to injury
aimed at stopping bleeding. Platelets aggregate at the site of injury to form a temporary plug, and blood vessels
constrict to reduce blood flow. This initial phase is crucial for preventing excessive blood loss and initiating the
healing process.
Inflammatory Phase: Neutrophils help to eliminate bacteria and debris through phagocytosis, while
macrophages play a key role in clearing cellular debris and secreting growth factors that promote tissue repair.
The inflammatory phase also involves the release of pro-inflammatory cytokines and chemokines, which recruit
additional immune cells to the site of injury.
Proliferative Phase: The proliferative phase is marked by the formation of new tissue and the restoration of the
wound bed. Fibroblasts migrate to the wound site and produce collagen, the main structural protein in
connective tissue, to form granulation tissue. This tissue provides a scaffold for new blood vessels and epithelial
cells to grow into the wound bed. Additionally, epithelial cells at the wound edges proliferate and migrate across
the wound surface to form a new epithelial layer, a process known as re-epithelialization.

10. Continued…..
Remodeling Phase: The final phase of wound healing is the remodeling phase, during which the newly
formed tissue undergoes remodeling and maturation. Excess collagen is broken down by matrix
metalloproteinases (MMPs), and the collagen fibers undergo cross-linking to increase tensile strength. The
wound undergoes contraction, reducing its size, and the vascular network matures to restore blood flow.
This phase can last for months to years, depending on the size and severity of the wound.
Regulation by Growth Factors and Cytokines: Throughout the wound healing process, various growth
factors and cytokines play critical roles in coordinating cellular activities and modulating the immune
response.
Extracellular Matrix Deposition: The extracellular matrix (ECM) provides structural support for cells and
facilitates cell migration and signaling during wound healing. Components of the ECM, such as collagen,
fibronectin, and hyaluronic acid, are synthesized and deposited by fibroblasts to form the provisional matrix
and later the mature scar tissue.

11. Thank
You