This document discusses plasma derived mediators, including the kinin system, complement system, and clotting system. These three interrelated systems are triggered by activation of Hageman factor (Factor XII) in the coagulation cascade. Key mediators produced include bradykinin, which is a potent vasodilator, and components of the coagulation system like thrombin and fibrin, which form blood clots that stop bleeding and provide structure for healing.

1. PLASMA DERIVED MEDIATORS

2.  Most mediators act through cell surface receptors.
Exceptions are those that have a direct enzymatic
effect (lysosomal enzymes) or direct toxic effect
(reactive oxygen species).
 Stimulus response coupling leads to biological
response.
 Mediators can stimulate target cells to release
secondary mediators.
 Mediators are short lived. They are rapidly inactivated
(helps prevent harmful effects).

3.  Series of inactive proteins circulating in the plasma
that are converted to proteolytic enzymes that activate
other proteins.
 Plasma Proteases:
 Interrelated systems that are triggered by activation of
Hageman factor (Factor XII of the coagulation
cascade). Activated by endotoxin, activated platelets or
contact of plasma with damaged tissue (collagen,
basement membrane).

4.  3 interrelated systems are active within this
category
1. Kinin system
 Highly vasoactive
2. Complement system
 Vasoactive
 Chemotactic
3. Clotting system
 Vasoactive
 Cleaves C3

5.  Factor XII of intrinsic coagulation cascade
 Activated by
 Negatively charged surfaces
 Platelets
 Proteases from inflammatory cells
 Causes
 Coagulation
 Activation of fibrinolytic system
 Produces bradykinin
 Activates complement
 Provides an amplification system

7. Activated by Hageman factor (XIIa)
 Bradykinin
 Release of vasoactive nonapeptide bradykinin
 Generated from the plasma
 Potent vasodilator
 Increased vascular permeability
 Contraction of smooth muscle
 Produce pain
 Stimulates release of histamine
 Activates the arachidonic acid cascade

9.  Coagulation (clotting) system
 Forms a fibrinous meshwork at an injured or inflamed
site
 Prevents the spread of infection
 Keeps microorganisms and foreign bodies at the site of
greatest inflammatory cell activity
 Forms a clot that stops bleeding
 Provides a framework for repair and healing
 Main substance is an insoluble protein called fibrin

10.  results in production of thrombin, factor Xa and
formation of fibrinopeptides
 thrombin cleaves fibrinogen to form fibrin and
enhances leukocyte adhesion
 fibrinopeptides are chemotactic and increase vascular
permeability
 factor Xa increases vascular permeability and
leukocyte emigration

12.  The blood clotting system or coagulation pathway, like the
complement system, is a proteolytic cascade.
 Each enzyme of the pathway is present in the plasma as a
zymogen, in other words in an inactive form, which on activation
undergoes proteolytic cleavage to release the active factor from
the precursor molecule.
 The coagulation pathway functions as a series of positive and
negative feedback loops which control the activation process.
 The ultimate goal of the pathway is to produce thrombin, which
can then convert soluble fibrinogen into fibrin, which forms a
clot.
 The generation of thrombin can be divided into three phases,
the intrinsic and extrinsic pathways that provide alternative
routes for the generation of factor X, and the final common
pathway which results in thrombin formation