648
UNIT 4
Maintenance of the Body
17
intermediates of both pathways can be activated only in the
presence of PF
3
. Te intermediate steps of each pathway
cascade
toward a common intermediate, factor X (Figure 17.14). Once
factor X has been activated, it complexes with calcium ions, PF
3
,
and factor V to form
prothrombin activator
. Tis is usually the
slowest step of the blood clotting process, but once prothrombin
activator is present, the clot forms in 10 to 15 seconds.
Te intrinsic and extrinsic pathways usually work together
and are interconnected in many ways, but there are significant
differences between them. Te
intrinsic pathway
is
Called
intrinsic
because the factors needed for clotting are
present
within
(intrinsic to) the blood.
±riggered by negatively charged surfaces such as activated
platelets, collagen, or glass. (Tis is why this pathway can
initiate clotting in a test tube.)
Slower because it has many intermediate steps.
Te
extrinsic pathway
is
Called
extrinsic
because the tissue factor it requires is
outside
of blood.
±riggered by exposing blood to a factor found in tissues un-
derneath the damaged endothelium. Tis factor is called
tis-
sue factor (TF)
or
factor III
.
Faster because it bypasses several steps of the intrinsic path-
way. In severe tissue trauma, it can form a clot in 15 seconds.
Phase 1 ends with the formation of a complex substance
called
prothrombin activator
.
Phase 2: Common Pathway to Thrombin
Prothrombin activator catalyzes the conversion of a plasma pro-
tein called
prothrombin
into the active enzyme
thrombin
.
Phase 3: Common Pathway to the Fibrin Mesh
Te end point of phase 3 is a
fibrin mesh
that traps blood cells
and effectively seals the hole until the blood vessel can be per-
manently repaired. Trombin catalyzes the transformation of
the
soluble
clotting factor
fibrinogen
into
fibrin
. Te fibrin
molecules then polymerize (join together) to form long, hair-
like,
insoluble
fibrin strands. (Notice that, unlike other clotting
factors, activating fibrinogen does not convert it into an en-
zyme, but instead allows it to polymerize.) Te fibrin strands
glue the platelets together and make a web that forms the struc-
tural basis of the clot. Fibrin makes the liquid plasma become
gel-like and traps formed elements that try to pass through it
(Figure 17.15)
.
In the presence of calcium ions, thrombin also activates
factor
XIII (fibrin stabilizing factor)
, a cross-linking enzyme that binds
the fibrin strands tightly together, forming a fibrin mesh. Cross-
linking further strengthens and stabilizes the clot, effectively seal-
ing the hole until the blood vessel can be permanently repaired.
Factors that inhibit clotting are called
anticoagulants
.
Whether or not blood clots depends on a delicate balance
between clotting factors and anticoagulants. Normally, an-
ticoagulants dominate and prevent clotting, but when a ves-
sel is ruptured, clotting factor activity in that area increases
Vessel endothelium
ruptures, exposing
underlying tissues
(e.g., collagen)
PF
3
released by
aggregated
platelets
XII
XI
IX
XII
a
Ca
2+
Ca
2+
Ca
2+
Ca
2+
XI
a
IX
a
Intrinsic pathway
Phase 1
Phase 2
Phase 3
Tissue cell trauma
exposes blood to
Platelets cling and their
surfaces provide sites for
mobilization of factors
Extrinsic pathway
Tissue factor (TF)
X
X
a
Prothrombin
activator
Cross-linked
fibrin mesh
Prothrombin (II)
Thrombin (II
a
)
Fibrinogen (I)
(soluble)
Fibrin
(insoluble
polymer)
PF
3
VII
VII
a
TF/VII
a
complex
IX
a
/VIII
a
complex
VIII
VIII
a
V
V
a
XIII
XIII
a
Figure 17.14
The intrinsic and extrinsic pathways of blood
clotting (coagulation).
The subscript “a” indicates the activated
clotting factor (procoagulant).
Pivotal components in both pathways are negatively charged
membranes, particularly those of platelets, that contain phos-
phatidylserine, also known as
PF
3
(platelet factor 3). Many
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