Physiology of blood coagulation. General Physiology

1. General Physiology
WinnerzKlub

2.  Clotting takes place in 3 essential steps:
 In response to rupture of vessel/damage to
blood itself, a complex cascade of chemical
rxns occurs in the blood-net result; formation
of Prothrombin Activator.
 Prothrombin activator catalyzes conversion of
prothrombin into thrombin.
 The thrombin acts as an enzyme to convert
fibrinogen into fibrin-fibers that enmesh
platelets, blood cells, & plasma to form the
clot.

3.  First, prothrombin activator is formed as a result
of rupture of a blood vessel or as a result of
damage to special substances in the blood.
 Second, prothrombin activator in the presence of
sufficient amounts of ionic Ca++, causes
conversion of Prothrombin into Thrombin.
 Third, thrombin causes polymerization of
fibrinogen molecules into fibrin fibers.
 NB: The rate-limiting factor in causing blood
coagulation is usually the formation of
prothrombin activator & not the subsequent rxns
beyond that point.

4.  Is a plasma protein formed continually by the
liver.
 An unstable protein that can split easily into
smaller compounds, one of which is thrombin.
 Vitamin K is required by the liver for normal
activation of prothrombin, as well as a few
other clotting factors.
 Therefore, either lack of Vit K or the presence
of liver disease that prevents normal
prothrombin formation can results in bleeding.

5. Thrombin is a protein enzyme with weak
proteolytic capabilities that acts on
fibrinogen to form multiple fibrin monomer
(s) that has ability to polymerize with other
fibrin monomer molecules to form fibrin
fibers.

6. Thrombin also activates the Fibrin-
Stabilizing-Factor (a substance present in
small amounts in normal plasma globulins
also from platelets entrapped in the clot).
Fibrin Stabilizing Factor then acts as an
enzyme to cause covalent bonds btw more
& more of the fibrin monomer molecules,
thus adding strength to the 3-D fibrin
meshwork.

7. The clot is composed of a meshwork of
fibrin fibers running in all directions &
entrapping blood cells, platelets, & plasma.
The fibrin fibers also adhere to damaged
surfaces of blood vessels; therefore, the
blood clot becomes adherent to any
vascular opening & thereby prevents
further blood loss.

8. After clot is formed, it begins to contract &
expresses most of the fluid from the clot
within 20-60mins.
The fluid expressed is Serum-all its
fibrinogen & most of the other clotting
factors have been removed. (plasma vs.
serum)
NB: Platelets are necessary for clot
retraction to occur.

9. Once a critical amount of thrombin is
formed, a positive feedback kicks in that
causes still more blood clotting & more &
more thrombin to be formed.
Thrombin has a PROTEOLYTIC ACTION
that allows it to act on many of the other
blood-clotting factors in addition to
fibrinogen.
Has a direct proteolytic effect on
prothrombin itself, tending to convert this
into still more thrombin.

10. Sources:
 Tortora, 15th Ed.
 Guyton and Hall, Medical Physiology. 12th Ed.