Blood, Heart, and Circulation 435bedridden, blood accumulates in the veins and causes them to
bulge. When a person is more active, blood returns to the heart
at a faster rate and less is left in the venous system.
Action of the skeletal muscle pumps aids the return of venous
blood from the lower limbs to the large abdominal veins. Move-
ment of venous blood from abdominal to thoracic veins, how-
ever, is aided by an additional mechanism—breathing. When a
person inhales, the diaphragm—a muscular sheet separating the
thoracic and abdominal cavities—contracts. Contraction of the
dome-shaped diaphragm causes it to flatten and descend inferi-
orly into the abdomen. This has the dual effect of increasing the
pressure in the abdomen, thus squeezing the abdominal veins,next Clinical Application Box). Capillary growth may addition-
ally be promoted by adenosine (derived from AMP), which also
stimulates vasodilation of arterioles and thereby increases blood
flow to the hypoxic tissue. These changes result in a greater
delivery of oxygen-carrying blood to the tissue.
CLINICAL APPLICATION
Angiogenesis refers to the formation of new blood vessels
from preexisting vessels, usually venules. This is needed
because cells must be within 100 m m of a capillary to sur-
vive. Angiogenesis is required for the growth of neoplasms
(tumors), and is involved in the development of neovascu-
lar age-related macular degeneration, also known as wet
macular degeneration (chapter 10, section 10.7). Inhibi-
tion of angiogenesis would thus aid the treatment of these
conditions.
Two paracrine regulators, fibroblast growth factor
( FGF ) and vascular endothelial growth factor ( VEGF ),
bind to tyrosine kinase receptors (chapter 11; see fig. 11.11)
to stimulate angiogenesis. The FDA has approved the use of
a monoclonal antibody (chapter 15, section 15.4) prepara-
tion called bevacizumab ( Avastin ), which binds to and inacti-
vates VEGF, for the treatments of cancers of the colon, lung,
breast, cervix, ovaries, and kidneys. Ranibizumab ( Lucentis ),
another monoclonal antibody preparation against VEGF, can
be injected into the vitreous humor of the eye to inhibit the
angiogenesis of wet macular degeneration.Veins
Most of the total blood volume is contained in the venous sys-
tem. Unlike arteries, which provide resistance to the flow of
blood from the heart, veins are able to expand as they accu-
mulate additional amounts of blood. The average pressure in
the veins is only 2 mmHg, compared to a much higher average
arterial pressure of about 100 mmHg. These values, expressed
in millimeters of mercury, represent the hydrostatic pressure
that the blood exerts on the walls of the vessels.
The low venous pressure is insufficient to return blood to
the heart, particularly from the lower limbs. Veins, however,
pass between skeletal muscle groups that provide a massaging
action as they contract ( fig. 13.29 ). As the veins are squeezed
by contracting skeletal muscles, a one-way flow of blood to the
heart is ensured by the presence of venous valves. The ability
of these valves to prevent the flow of blood away from the heart
was demonstrated in the seventeenth century by William Har-
vey ( fig. 13.30 ). After applying a tourniquet to a subject’s arm,
Harvey found that he could push the blood in a bulging vein
toward the heart, but not in the reverse direction.
The effect of the massaging action of skeletal muscles on
venous blood flow is often described as the skeletal muscle
pump. The rate of venous return to the heart is dependent,
in large part, on the action of skeletal muscle pumps. When
these pumps are less active, as when a person stands still or is
Valve openValve
closedVeinValve
closedVeinContracted
skeletal
musclesRelaxed
skeletal
musclesTo heartTo heartFigure 13.29 The action of the oneway venous
valves. Contraction of skeletal muscles helps to pump blood
toward the heart, but the flow of blood away from the heart is
prevented by closure of the venous valves.