Acute inflammation – B. Pharma 2nd Semester Pathophysiology notes pdf

Acute inflammation

Acute-inflammation

Objective

At the end of this PDF, student will be able to

         Explain the main processes of cellular phase of inflammatory response

        Describe the events taking place in the cellular phase

•     Explain the fate of acute inflammation

Acute inflammation

Cellular events in acute inflammation

Cellular phases of inflammation comprises of two processes

       Exudation of leucocytes

       Phagocytosis

Cellular-events-in-acute-inflammation

Exudation of leucocytes

1. Changes in the formed elements of blood

       Early stage of inflammation

       Increased rate of blood flow – vasodilatation – slowing or stasis of bloodstream

       Central stream of cells widens and peripheral plasma zone becomes narrower – exudation

       Margination – redistribution – neutrophils of the central column come close to the vessel wall – pavementing

2. Rolling and adhesion:

Selectins – Helps rolling of neutrophills  over endothelial cells

       P-selectin – rolling

       E-selectin – associated with both rolling and adhesion

      L-selectin – responsible for homing of circulating lymphocytes to the endothelial cells in lymph nodes

Integrins

       Activated during the process of loose and transient adhesions

       Between endothelial cells and leucocytes

       Stimulation receptors for integrins on the neutrophils

       Firm adhesion between leucocyte and endothelium

Immunoglobulin gene superfamily adhesion molecule intercellular adhesion molecule-1 (ICAM-1),

       Vascular cell adhesion molecule-1 (VCAM-1) – tighter adhesion and stabilise the interaction between leucocytes and endothelial cells

       Platelet-endothelial cell adhesion molecule- 1 (PECAM-1) or CD31 – leucocyte migration from the endothelial surface

3. Emigration and diapedesis :

       Sticking of neutrophils to the endothelium

       Movement along the endothelial surface

       Cytoplasmic pseudopods – cross the basement membrane – damage – collagenases – extravascular space – emigration

       Neutrophils are dominant first 24 hours

       Monocyte-macrophages  – 24-48 hours

Diapedesis – passive phenomenon

       RBCs being forced out

       Raised hydrostatic pressure

       Escape through the endothelial defects

       Diapedesis gives haemorrhagic appearance to the inflammatory exudate

4. Chemotaxis:

Chemotactic factor-mediate transmigration of leucocytes

       Leukotriene B4 (LT-B4)

       Components of complement system (C5a and C3a)

       Cytokines (Interleukins, in particular IL-8)

       Soluble bacterial products (such as formylated peptides)

       Chemokines e.g. monocyte chemoattractant protein (MCP-1), eotaxin – eosinophils, NK cells-  virally infected cells

Chemotaxis

Phagocytosis

Engulfment of solid particulate material by the cells – phagocytes

       Polymorphonuclear neutrophils (PMNs) – acute inflammatory response – microphages

       Circulating monocytes and fixed tissue mononuclear phagocytes –  macrophages

Process involves 4 stages

       Recognition and attachment

       Engulfment

       Degranulation

       Killing and degradation

1.   Recognition and attachment

       Phagocytes & microorganism – have similar charges

       Phagocytes covered with opsonin to facilitate bond

       IgG opsonin

       C3b fraction of complement system

2. Engulfment

       After opsonisation, particle ready to be engukfed

       Cytoplasmic pseuodopods extend out from phagocytes

       Phagocytic vacuole

       Plasma membrabe enclosing phagocytic vacuole breaks

       Engulfed material lies free in cytoplasm

       Lysosome + Phagocytic vacuole = Phagolysosome

3.  Secretion (Degranulation)

       Enzyme stored with in preformed granule are secreted into phagosome & extracellular environment

       Primary or azurophillic granules – fuse with lysosome

       Secondary or specific granules are discharged

4. Killing and degradation

Microorganisms – killed by antibacterial substances – degraded by hydrolytic enzymes

       Oxygen dependent bactericidal mechanism

       Oxygen independent bactericidal mechanism

       Nitric oxide

MPO-dependent killing:

MPO-dependent-killing

       Enzyme MPO acts on hydrogen peroxide in the presence of halides to form corresponding hypohalous acid – potent antibacterial

MPO-dependent-killing


MPO  independent bactericidal mechanism

       Mature macrophages lack the enzyme MPO

       OH  – Bactericidal activity

MPO-independent-bactericidal-mechanism


Oxygen independent killing bactericidal mechanism:

       Liberated lysosomal granules –

       lysis within phagosomes – 

       lysosomal hydrolases,

       permeability increasing factors,

       cationic proteins (defensins),

       lipases, ptoteases, DNAases

Nitric oxide:

       Endothelial cells and activated macrophages

       Nitric oxide reactive free radicals – nitric oxide synthase –  potent mechanism of microbial killing

Fate of acute inflammation

Fate-of-acute-inflammation

Summary

       Cellular phases of inflammation comprises of two processes -exudation of leucocytes and phagocytosis

       Exudation of leucocytes involves-  changes in formed elements, rolling & adhesion, emmigration& diaphesis and invasion

       Phagocytosis involves cell eating

       Fate of acute inflammation may be healing, regeneration, suppuration or may develop into chronic inflammation

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