Chemical mediators of inflammation – B. Pharma 2nd Semester Pathophysiology notes pdf

Chemical mediators of inflammation

Contents

       Chemical mediators of inflammation

       Cell derived mediators

       Plasma derived mediators

Objectives
 

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

         List various chemical mediators of inflammation

         Describe the 
formation and functions of cell derived mediators

        Describe the formation and functions of plasma
derived mediators

Chemical
mediators of inflammation

       Endogenous compounds

       Released during inflammation

       Increases vascular permeability

       Edema, Destruction of inflammatory agents

Cell derived mediators 

of inflammation

       Vasoactive amines – Histamine, Serotonin,
Neuropeptides

       Arachidonic acid metabolites

      Via COX pathway – Prostaglandins, Thromboxane A2, prostacyclin

      Via LOX pathway – 5-HETE, leukotrienes

       Lysosomal system

       Platelet activating factor

       Nitric oxide and oxygen metabolites

Plasma
derived mediators of inflammation

       The kinin system

       The clotting system

       The fibrinolytic system

       The complement system

Vasoactive amines (Autocoids)

Amine autocoids

       Histamine

       5 – HT / Serotonin

Released within 1 hour
of inflammatory response

 Histamine

       Stored in mast cells, basophills &
platelets

Released due to –
Heat/cold radiations

      Chemical irritant & immunological reactions

      Anaphyla toxins

Main actions of
Histamine

       Vaso dilation

       ↑ permeability of venules

       Itching & pain

       Release of other cell derived mediators

       Broncho constriction

Serotonin

       Present in chromaffin cells of GIT

       In spleen, nervous system, mast cells &
platelets

Actions

       Vasodilation

       ↑vascular permeability

       Less potent than histamine

Neuropeptides

       Tachykinin neuropeptides – substance P, neurokinin A, vasoactive
intestinal polypeptide (VIP) & somatostatin

       Produced in the central and peripheral nervous systems

Actions

       Increased vascular permeability

       Transmission of pain stimuli

       Mast cell degranulation

Arachdonic acid Metabolite

       Tissue injury – Phospholipase A2
activation

       Conversion of phospholipids into arachdonic
acid 

Metabolism of
arachdonic acid follows 2 pathway

       COX (Cyclo-oxygenase) – Pathway

       LOX (Lipo- oxygenase) – Pathway

COX Pathway

LOX Pathway

Lysosomal components

Granules of
Neutrophills

Primary granules 

·        
Myeloperoxidase

·        
Acid
hydrolase

·        
Neutral
proteases

Secondary granules

·        
Lactoferrin

·        
Lysozyme

·        
Alkaline
phosphatase

·        
Collagenase

Granules of
Monocytes & Tissue macrophages

       Cells on degranulation releases mediators like

       Acid proteases

       Collagenase

       Elastase

       Plasminogen activator

More involved in
chronic inflammation

Platelet Activating Factor (PAF)

IgE-sensitised
basophils or mast cells, other leucocytes, endothelium and platelets

      
↑ vascular permeability

      
Vasodilatation in low concentration and vasoconstriction

      
Broncho constriction

      
Adhesion of leucocytes to endothelium

      
Chemotaxis

Cytokines

      
Group of polypeptide substances

      
Produced by activated lymphocytes/ monocytes

      
Interleukin 1 & 8

      
Tumor necrosis factor

      
Interferon

      
Platelet factor

Actions:

      
IL –I, TNF α
& β
– ↑ leucocyte adherence, Platelet aggregation, proliferation of fibroblast

      
Interferon gamma – activation of macrophages & neutrophils

      
IL-8 – Chemotactic of neutrophills

      
PF – 4 – Chemotactic for neutrophills, monocytes & eosinophills

Nitric oxide & oxygen metabolites

      
Released by activated macrophages from vascular endothelium

      
Vasodilation

      
Inhibiton of platelet aggregation

      
Killing of micro organism

      
O2 free radicals released from activated neutrophills &
macrophages

      
Endothelial damage

      
↑vascular permeability

      
Tissue matrix damage

Plasma derived mediators

      
Interlinked system

      
Include

     
Clotting system

     
Kinin system

     
Fibrinolytic system

     
Complement system

      
Hageman factor (Factor XII) – connects the other 4 system

Clotting system

      
Results in formation of fibrinogen

      
Thrombin converts fibrinogen to fibrin & fibrinopeptide

     
↑ vascular permeability

     
Chemotaxis of leucocytes

     
Anticoagulant activity

Fibrinolytic system

      
Activated by plasminogen

      
Plasminogen activator – plasminogen – plasmin-  breakdown of fibrin –  fibrinopeptides or fibrin split products

Actions

     
Activation of factor XII

     
Splits complement fraction C3to C3a– permeability factor

     
Degrade fibrin to form fibrin split products

Complement system

Involves
2 pathways

      
Classic pathway through antigen-antibody complexes

      
Alternate pathway via non-immunologic agents such as bacterial toxins,
cobra venoms and IgA

Anaphylatoxins
(C3a, C5a, C4a)

     
Activate mast cells and basophils to release of histamine

     
cause increased vascular permeability

     
augments phagocytosis

      
C3b – an opsonin

      
C5a –  chemotactic for leucocytes

      
Membrane attack complex (MAC) (C5b-C9) is a lipid dissolving agent and
causes holes in the phospholipid membrane

Chemical mediators of inflammation

Summary

      
Chemical mediators are endogenous compounds released during inflammation
which increases vascular permeability, bring about edema and destruction of
inflammatory agents

      
Chemical mediators of inflammation are derived from cell and plasma

      
Cell derived mediators include histamine, serotonin, leukotrienes,
platelet activating factors, cytokinines, prostaglandins

      
Plasma derived mediators include kinin system, cltting and fibrinolytic
system and clotting system

Leave a comment