PLASMA DERIVED CHEMICAL

MEDIATORS OF INFLAMMATION

These include various products derived from activation and interaction of 4 interlinked systems

1)Kinin2)Clotting3)Fibrinolytic and Complement

EACH OF THESE SYSTEMS HAS ITS INHIBITORS AND ACCELERATORS IN PLASMA WITH NEGATIVE AND POSITIVE FEEDBACK MECHANISMS.....

INTRODUCTION

Hageman factors(factor xii) of clotting system plays a key role in interactions of four systems. Activation of factor xii in vivo by contact with basement mambrraneand bacterial endotoxins and in vitro with glass or kaolin leads to activation of cloyying,fibrinolytic and kinin systems. In inlammation activation of factorxii is brought about by contact of the factor leaking through the endothelial gaps.The end products of the clotting,fibrinolytic and kinin system activate the complememtsystem that genetrate permeability factors,in turn,further activates clotting system.

FACTOR XII

FACTOR XIIa

FIBRIONOLYTIC SYSTEM

CLOTTING SYSTEM

KININ SYSTEM

PLASMIN FIBRIN BRADYKININ

FIBRIN SPLIT PRODUCTS

COMPLEMENTARY SYSTEM PERMEABILITY FACTORS

I)THE KININ SYSTEM This system on activation by factor xiia genetrates bradykinin, so named

because of smoth muscle it induces.First kallikrein is formed from prekallilrein by theaction of prekallikrein which is a fragment of factor xiia kallikrein then acts on high molecular weight kininogen to form bradykinin.Bradykinin acts in the early stage and its effects include:

1. Smooth muscle contaction 2. Vasodialation3. Increased vascular permeability4. Pain

II)THE CLOTTING SYSTEM

FACTOR XIIa initiates the clotting cascade of the clotting system resulting in formation of fibrionogenwhich is acted upon by thrombin to form fibrin and fibrinopeptides the actions of fibrionopeptides in inflammtion are:

1. Increased vascular permeability2. Chemotaxis for leucocyte3. And anti coagulant activity

III)THE FIBRINOLYTIC SYSTEM

This system is activated by plasminogen activator the source of which includekallikrein of the kinin system,endothelial cells and leucocytes.Plasminogen activator acts on plasminogen prresnt as component of plasma proteins to form plasmin. Further breakdown of fibrin by plasma forms fibrinopeptides or fibrin split products

THE ACTIONS OF PLASMIN IN INFLAMMTION ARE-

1. Activation of factor xii to form prekallikrein activator that stimulates the kinin system to generate bradykinin;

2. Splits off complement c3 to form c3a which is a permeability factor;3. Degrades fibrin to form fibrin split products which increase vascular permeability and

are chemotactic to leucocytes.

IV)THE COMPLEMENT SYSTEM

The activation of complement system can occur either;

1)by classic pathway through antigen-antibody complex2) by alternate pathway via non-immunologic agents such as bacterial

toxins,cobra venoms and Iga.

Complement system on activation by either of these two pathways yields anaphylatoxins c3a,c4a and c5a and membrane attack complex(mac).

The relative potancies of anaphylatoxins are in descending sequence of c3a,c5a and c4a

The action of anaphylatoxins in inflammataion are;

1. Release of histamine from mast cells and basophills;

2. Incresead vascular permeability causing oedema in tissues

3. C3b augments phagocytosis and

4. C5a is chemotactic for leucocytes

The action of MAC is to cause pores in the cell membrane of the invading microorganism

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