Cardiovascular Physiology
431
Hemostasis: The Prevention
of Blood Loss
The stoppage of bleeding is known as
hemostasis
(don’t con-
fuse this word with homeostasis). Physiological hemostatic
mechanisms are most effective in dealing with injuries in small
vessels—arterioles, capillaries, and venules, which are the most
common source of bleeding in everyday life. In contrast, the
body usually cannot control bleeding from a medium or large
artery. Venous bleeding leads to less rapid blood loss because
veins have low blood pressure. Indeed, the drop in pressure
induced by raising the bleeding part above the heart level may
stop hemorrhage from a vein. In addition, if the venous bleed-
ing is internal, the accumulation of blood in the tissues may
increase interstitial pressure enough to eliminate the pressure
gradient required for continued blood loss. Accumulation of
blood in the tissues can occur as a result of bleeding from any
vessel type and is known as a
hematoma
.
When a blood vessel is severed or otherwise injured, its
immediate inherent response is to constrict (the mechanism is
unclear). This short-lived response slows the fl ow of blood in the
affected area. In addition, this constriction presses the opposed
endothelial surfaces of the vessel together, and this contact
induces a stickiness capable of keeping them “glued” together.
Permanent closure of the vessel by constriction and con-
tact stickiness occurs only in the very smallest vessels of the
microcirculation, however, and the staunching of bleeding
ultimately depends upon two other interdependent processes
that occur in rapid succession: (1) formation of a platelet plug;
and (2) blood coagulation (clotting). The blood platelets are
involved in both processes.
Formation of a Platelet Plug
The involvement of platelets in hemostasis requires their adhe-
sion to a surface. Injury to a vessel disrupts the endothelium
and exposes the underlying connective tissue collagen fi bers.
Platelets adhere to collagen, largely via an intermediary called
von Willebrand factor (vWF),
a plasma protein secreted by
endothelial cells and platelets. This protein binds to exposed
collagen molecules, changes its conformation, and becomes
able to bind platelets. Thus, vWF forms a bridge between the
damaged vessel wall and the platelets.
Binding of platelets to collagen triggers the platelets to
release the contents of their secretory vesicles, which contain
a variety of chemical agents. Many of these agents, including
adenosine diphosphate (ADP) and serotonin, then act locally to
induce multiple changes in the metabolism, shape, and surface
proteins of the platelets, a process called
platelet activation.
Some of these changes cause new platelets to adhere to the old
ones, a positive feedback phenomenon termed
platelet aggre-
gation,
which rapidly creates a
platelet plug
inside the vessel.
Chemical agents in the platelets’ secretory vesicles are
not the only stimulators of platelet activation and aggre-
gation. Adhesion of the platelets rapidly induces them to
synthesize
thromboxane A
2
,
a member of the eicosanoid
family, from arachidonic acid in the platelet plasma mem-
brane. Thromboxane A
2
is released into the extracellular fl
uid
and acts locally to further stimulate platelet aggregation and
release of their secretory vesicle contents (
Figure 12–72
).
Fibrinogen, a plasma protein whose essential role in
blood clotting is described in the next section, also plays a
crucial role in the platelet aggregation produced by the fac-
tors previously described. It does so by forming the bridges
between aggregating platelets. The receptors (binding sites)
for fi
b
r
inogen
on
the
p
la
te
le
t
p
lasma
memb
rane
become
exposed and activated during platelet activation.
The platelet plug can completely seal small breaks in
blood vessel walls. Its effectiveness is further enhanced by
another property of platelets—contraction. Platelets contain
a very high concentration of actin and myosin (Chapter 9),
which are stimulated to contract in aggregated platelets. This
causes compression and strengthening of the platelet plug.
(When they occur in a test tube, this contraction and com-
pression are termed
clot retraction.
)
While the plug is being built up and compacted, the vas-
cular smooth muscle in the damaged vessel is being stimulated
to contract (see Figure 12–72), thereby decreasing the blood
fl ow to the area and the pressure within the damaged vessel.
This vasoconstriction is the result of platelet activity, for it is
mediated by thromboxane A
2
and by several chemicals con-
tained in the platelet’s secretory vesicles.
Once started, why does the platelet plug not continu-
ously expand, spreading away from the damaged endothelium
Begin
Blood vessels
Contraction of vascular smooth muscle
Discharge
of mediators
Synthesis of
thromboxane A
2
Platelets
Activation and
aggregation
Chemical
mediators
Thromboxane A
2
Altered endothelial surface
(collagen exposed)
Vasoconstriction
Platelet plug
Vessel damage
+
+
Figure 12–72
Sequence of events leading to formation of a platelet plug and
vasoconstriction following damage to a blood vessel wall. Note the
two positive feedbacks in the pathways.
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