The Circulation

systemic circulation = blood flow to all tissues in the body

except lungs(greater circulation or peripheral circulation)
pulmonary circulation

Functional parts
Arteries transport blood under high pressure to tissues (thus
strong vascular walls, blood flows at high velocity in arteries)
- arterioles are last small branches, act as control condiuits ->
strong muscular wall, relax, dilate, constrict
capillaries exchange fluid, nutrients, etc. Thus are thin and
have pores permeable
Venules collect blood from capillaries, coalesce to larger
veins
Veins conduits for transport of blood from venules back to
heart and serve as a major reservoir for extra blood. Low
pressure, venous walls are thin but are muscular enough to

contract or expand and act as controllable reservoir for extra

blood
Larger cross sectional area in veins than arteries -> large storage
for blood.
Also capillaries have short time for diffusion.
Velocity of blood flow is inversely proportional to vascular cross
sectional area
Pressures
mean pressure in aorta is high (100). As blood flows through
systemic circulation, mean pressure falls to 0 by the time it
reaches termination of venae cavae where they empty into RA
of the heart.
Pressure in systemic capillaries varies from 35 near arteriolar
ends to as low as 10 near the venous ends but their average
functional pressure in most vascular beds is about 17, a
pressure low enough that little of the plasma leaks through
minute pores of the capillary walls.

In pulmonary arteries, pressure is pulsatile but lower (25

systolic, 8 diastolic). Mean pulmonary capillary pressure
averages only 7. Yet total blood flow through lungs is same as
systemic circulation. Low pressure is because all that is
needed is to expose blood to oxygen

Basic theory
1) rate of blood flow to each tissue of body is precisely controlled
in relation to the tissue need: dilate or constrict to control
local blood flow because heart cannot simply increase CO to 47 times during active needs. Nervous control from CNS also
helps
2) CO is controlled mainly by sum of all local tissue flows
3) AP is controlled independently of either local blood flow
control or cardiac output control: nervous signals can increase
force of pumping, cause contraction of large venous reservoirs
to provide more blood to heart, cause generalized constriction
of most of arterioles so more blood accumulates in large
arteries to increase AP, kidneys also secrete hormones to
regulate blood volume
Blood flow, pressure

determined by pressure difference of blood between two ends

of the vessel, vascular resistance
F = P/R
Blood flow is just the quantity of blood that passes a given
point in the circulation in a given period
Blood pressure means the force exerted by the blood against
any unit area of the vessel wall
Resistance is the impediment to blood flow in a vessel
rate of blood flow through entire circulatory system is equal to
rate of blood pumping by heart (CO)
resistance of entire systemic circulation is total peripheral
resistance
in conditions in which all blood vessels throughout the body
become strongly constricted, the total peripheral resistance
rises.
conductance: is a measure of blood flow through a vessel for a
given pressure difference. Conductance = 1/resistance
slight changes in diameter of a vessel cause changes in vessel
ability to conduct blood when blood flow is streamlined
importance of vessel diameter in determining arteriolar
resistance: in systemic circulation, 2/3 of total systemic
resistance to blood flow is arteriolar resistance in small
arterioles. However, strong vascular walls allow internal
diameters to change. Thus, arterioles by only responding to
small changes in diameter to nervous signals or local tissue

chemical signals can either turn off almost completely the

blood flow to tissue or to cause vast increase in flow
resistance to blood flow: the total peripheral vascular
resistance is equal to the sum of resistance of arteries,
arterioles, capillaries, venules and veins (when arranged in
series). But blood vessels branch extensively to form parallel
circuits that supply blood to many organs and tissues of the
body. This permits each tissue to regulate its own blood flow,
independently of flow to other tissues. Far greater amounts of
blood flow through parallel system than individual blood
vessels. Flow through each parallel vessel is determined by
pressure gradient and its own resistance not the resistance of
the other parallel blood vessels. However, increasing
resistance of any of the blood vessels increases total vascular
resistance.
Adding more blood vessels to a circuit reduces total vascular
resistance. Many parallel blood vessels make it easier for
blood to flow through the circuit because of providing another
pathway, or conductance, for blood flow

Blood hematocrit

the greater the viscosity, the less the flow in a vessel.

Suspended red cells exerts frictional drag against adjacent
cells and against the wall of the blood vessel
the percentage of blood that is cells is called hematocrit. The
viscosity of blood increases dramatically as the hematocrit
increases.
other factors affecting blood viscosity are the plasma protein
concentration and types of proteins in plasma but these are
less than the effect of hematocrit.

Effects of pressure on vascular resistance and tissue blood flow

increase in AP increases the force that pushes blood through

the vessels but also distends the vessels which decreases
vascular resistance. Thus greater pressure increases the flow
in both of these ways

Vascular Distensibility

all blood vessels distensible. When the pressure in blood

vessels is increased, this dilates the blood vessels and
therefore decreases their resistance. The result is increased
blood flow not only because of increased pressure but also
because of decreased resistance
vascular densibility also important in arteries to accommodate
pulsatile output of heart and average out the pressure

pulsations. This provides smooth, continuous flow of blood

through the very small blood vessels of the tissues
veins are most distensible. Therefore serve as reservoir. Artery
walls are so strong so not as distensible.
In pulmonary circulation, pulmonary vein distensibilities are
similar to systemic circulation. But pulmonary arteries operate
under less pressure than systemic arterial system and are
more distensible
Vascular compliance = increase in volume/increase in
pressure. This is the total quantity of blood that can be stored
in a given portion of the circulation. Compliance is equal to
distensibility x volume. Systemic veins have more compliance
than artery

Sympathetic systems: increase in vascular smooth muscle tone

caused by sympathetic stimulation increases the pressure at each
volume of the arteries or veins whereas sympathetic inhibition
decreases pressure at each volume. Increase in vascular tone
throughout systemic circulation causes large volumes of blood to
shift into heart -> increase heart pumping. Sympathetic control of
vascular capacitance is also important -> enhancement of
sympathetic tone, esp veins, reduces the vessel sizes enough that
the circulation continues
Delayed compliance (stress relaxation of vessels): vessel exposed to
increased volume at first exhibits large increase in pressure but
progressive delayed stretching allows pressure to return back to
normal.
Arterial pressure pulsations
if not for distensibility of the arterial system, new blood would
flow through peripheral blood vessels almost instantaneously.
However compliance of aterial tree reduces pressure
pulsations to no pulsations by the time it reaches capillaries.
Two factors affect pulse pressure: (1) stroke volume of heart
(2) compliance (total distensibility of arterial tree) and a third
less important factor is character of ejection from heart during
systole
- the greater the SV output, the greater the amount of blood
that must be accommodated in the arterial tree and therefore,
the greater the pressure rise and fall during systole and
diastole thus causing a greater pulse pressure.
- The less the compliance of the arteries, the greater the rise in
pressure for a given stroke volume of blood pumped into the
arteries
pulse pressure is determined by ratio of stroke volume output
to compliance of aterial tree. Any condition that affects either
of these two factors also affects pulse pressure
abnormal contours of pressure pulse wave occur:

aortic stenosis: diameter of aortic valve opening is reduced,

aortic pressure pulse is decreased significantly because of
diminished blood flow outward through stenotic valve
patent ductus arterosus: one half or more of the blood
pumped into the aorta by the LV flows backward through wide
open ductus into pulmonary artery and lung blood vessels,
allowing diastolic pressure to fall very low before next
heartbeat
aortic regurgitation, the aortic valve is absent or not closed
completely and therefore, blood pumped into aorta flows
backward into LV. As a result, aortic pressure can fall to zero
between heartbeats.

Transmission of pressure pulses

greater the compliance, the slower the velocity explaining the
slow transmission in the aorta and much faster transmission in
much less compliance small distal arteries.
Intensity of pulsation is less progressively in smaller arteries,
arterioles and capillaries. This is due to 1) resistance to blood
movement in vessels 2) compliance of vessels. Resistance
damps the pulsations because a small amount of blood must
flow forward at the pulse wave front to distend the next
segment of the vessel; the greater the resistance, the more
difficult it is for this to occur. The compliance damps the
pulsations because the more compliant a vessel, the greater
the quantity of blood required at the pulse wave front to cause
an increase in pressure
Mean AP is not equal to the average of systolic and diastolic
pressure because AP remains nearer to diastolic pressure than to
systolic pressure during the greater part of cardiac cycle. Therefore
mean AP is determined about 60% by diastolic pressure and 40% by
systolic pressure
Veins

veins can constrict and enlarge to store blood

peripheral veins can also propel blood forward by venous
pump to help regulate cardiac output

Venous pressures Right atrial pressure (central venous pressure)

and peripheral venous pressures

blood from all systemic veins flows into RA therefore pressure

in RA is called central venous pressure. RA pressure is
regulated by a balance between 1) ability of heart to pump
blood out of RA and ventricle into lungs and 2) tendency for
blood to flow form peripheral veins into RA.
if R heart is pumping strong, RA pressure decreases.

Any effect that causes rapid inflow of blood into RA from

peripheral veins elevates RA pressure. Factors include: 1)
increased blood volume, increased large vessel tone
throughout the body with resultant increased peripheral
venous pressure 2) dilation of arterioles which decreases
peripheral resistance and allows rapid flow of blood from
arteries into veins
The same factors that regulate RA pressure also enter into
regulation of CO
Normal RA pressure is about 0. But can increase in abnormal
conditions: 1) serious heart failure 2) after massive transfusion
of blood
Lower limit is about -3-5. This is when heart pumps with
extreme vigor or when blood flow into heart from peripheral
vessels is greatly depressed such as after severe hemorrhage

Venous resistance

large veins have so little resistance to blood flow when they

are distended that the resistance then is almost zero and is of
no importance. But some veins such as those coursing the
abdomen are compressed by different organs thus some large
veins do usually offer some resistance to blood flow. Because
of this, the pressure in the more peripheral small veins in a
person lying down is usually 4 6 greater than RA pressure
high RA pressure on peripheral venous pressure: when RA
pressure rises above normal value of 0, blood backs up in
large veins -> enlarges them. As RA pressure rises further,
additional increases causes rise in peripheral venous pressure
in limbs and elsewhere. As heart needs to weaken a bit to
reach RA pressures, peripheral venous pressure doesnt
elevate in early stages of heart failure
intrabdominal pressure on venous pressure of leg: when
intraabdominal pressure rises, the pressure in veins of the
legs must rise above the abdominal pressure before
abdominal veins will open and allow the blood to flow from
the legs to the heart

Venous valves and venous pumps

WHEN STANDING STILL => gravitational pressure -> pressure

in veins of feet is about +90 due to gravitational weight of
blood in veins between heart and feet. Pressure in RA is about
0
each time one moves the legs, one tightens the muscles and
compresses the veins or adjacent to the muscles and this
squeezes the blood out of the veins. This pumping allows
venous pressure in the feet of walking adult to be less than 20

If person is still, legs have 90 pressure. The pressures in the

capillaries also increase greatly causing fluid to leak from
circulatory system into tissue spaces. Legs swell and blood
volume diminishes.
Venous valve incompetence causes varicose veins: stretching
the veins increases cross sectional areas but leaflets of the
valves dont increase in size. Therefore, the leaflets of the
valves dont close completely. When this develops, the
pressure in the veins of the legs increase greatly because of
failure of the venous pump; this further increases the size of
the veins and destroys the function of the valves entirely.
when people with varicose veins stand, venous and capillary
pressure become high and leakage of fluid from capillaries
cause constant edema in the legs. The edema prevents
adequate diffusion of nutritional materials from capillaries to
muscle and skin cells.

Blood reservoir

nervous signals are elicited from carotid sinuses and other

pressure sensitive areas of circulation. This in turn elicit nerve
signals from the brain and spinal cord mainly through
sympathetic nerves to veins, causing them to constrict. This
takes up much of the slack in the circulatory system caused
by the lost blood
more extensive and compliant areas: 1) spleen which can
decrease in size to release blood to areas of circulation 2)
liver: sinuses can release blood 3) large abdo veins 4) venous
plexus beneath the skin.
heart and lungs, although not parts of systemic venous
reservoir, must also be considered blood reservoir. The heart
shrinks during sympathetic stimulation to provide blood, lungs
can contribute more when pulmonary pressures decrease to
low values
spleen: venous sinus, pulp. Sinuses can swell the same as any
part of venous system and store whole blood. In splenic pulp,
capillaries are permeable that whole blood including RBCs can
go in to form red pulp. These can be expelled into general
circulation whenever SNS is excited and causes spleen to
contract. In other areas are the pulp where lymphoid cells are
manufactured
removal of old cells: ruptured cells release hemoglobin and
cell stroma are digested by reticuloendothelial cells of spleen
and then reused by the body
reticuloendothelial cells of spleen: phagocytic cells to clean
blood.

Structure of microcirculation

each nutrient artery enters organ branches 6-8 times before

arteries become small enough to be called arterioles.
Arterioles branch 2-5 times where they supply blood to
capillaries
arterioles are highly muscular, diameters can change. The
metarterioles (terminal arterioles) dont have a continuous
muscular coat but smooth muscle fibers encircle the vessel at
intermittent points. At the point where each true capillary
originates from the metarteriole, a smooth muscle fiber
encircles the capillary (precapillary sphincter). This sphincter
can open and close the entrance to the capillary.
Venues are larger than arterioles and have a weaker muscular
coat. But pressure in venules is less than arterioles so that the
venules can contract despite weak muscle. Remember that
metarterioles and precapillary sphincters are in close contact
with tissues they serve so that they can control blood flow

Capillary wall: wall is composed of unicellular layer of endothelial

cells and is surrounded by a thin basement membrane on the
outside of the capillary.
Pores in capillary membrane: connect the interior of capillary with
exterior. Intercellular cleft lies at the bottom between adjacent
endothelial cells. Each cleft is interrupted by short ridges of protein
attachments that hold endothelial cells together but between these
ridges fluid can percolate freely through the cleft. Because they are
located at edges of the endothelial cells, they represent small
capillary wall but the rate of thermal motion of water molecules is so
rapid that they diffuse with ease between these slit pores, the
intercellular clefts.
Also present are plasmalemmal vesicles. These form at one surface
of the cell by imbibing small packets of plasma or ECF. Its also
postulated that some vesicles coalesce to form vesicular channels
all the way through the endothelial cell.

pores depend on organs:

1) in brain, junctions between capillary endothelial cells are
mainly tight junctions that allow only small molecules to pass
2) in liver, clefts between capillary endothelial cells are wide
open so almost all dissolved substances of the plasma can
pass through
3) pores of GIT are midway of those muscles and liver
4) glomerular tufts of kidney, fenetrate penetrate for filtration
and penetrate through middle of endothelial cells so they can
pass without passing through clefts between endothelial cells
Flow of blood in capillaries vasomotion

blood doesnt flow continuously through capillaries, flows

intermittently, turning on and off due to intermittent
contraction of metarterioles and precapillary sphincters
most important regulation is concentration of oxygen.
Despite the intermittent blood flow, so many capillaries are
present that overall function becomes averaged.
diffusion results from thermal motion of water molecules and
dissolved substances in the fluid.
If a substance is lipid soluble, it can diffuse directly through
cell membranes without pores. Their rates of transport will be
faster
Water soluble substances diffuse through intercellular pores in
membrane. Despite the fact that not more than 1/1000 of
surface area of capillaries is represented by the intercellular
clefts between endothelialcells, the velocity is so great that

even this small area is sufficient to allow tremendous diffusion

of water
Permeability of capillary pores for substances depends on size.
But different tissues have different permeability also
They net rate of diffusion of a substance through any
membrane is proportional to the concentration difference of a
substance.

Interstitium and ISF

about 1/6 of total volume of body is interstitum and the fluid

in these spaces is ISF
two major structures: 1) collagen fiber bundles and 2)
proteoglycan filaments. The collagen fiber bundles extend
long distances in the interstitum and are strong to provide
strength. The proteoglycans are thin twisted molecules and
are so thin
fluid in interstitium is derived from filtration and diffusion from
capillaries, with almost same plasma constituents except
proteins. ISF is entrapped mainly in minute spaces among
proteoglycan filaments.
Because of large number of proteoglycan filaments, its difficult
for fluid to flow easily through the gel so it mainly diffuses.
Diffusion is rapid because of short distances
There is some free fluid spaces, which allows free flow. These
areas are free from proteoglycan molecules. When the tissues
develop edema, these small pockets and rivulets of free fluid
expand tremendously

Fluid filtration
hydrostatic pressure forces fluid through
osmotic pressure by plasma proteins forces fluid movement
from interstitial spaces into blood. It normally prevents loss of
fluid
lymphatic system returns to circulation the small amounts of
excess protein and fluid that leak from blood and ISF
Starling forces:
1) capillary pressure which forces fluid outward through capillary
membrane
2) ISF pressure which forces fluid inward thorugh capillary
membrane
3) Capillary plasma colloid osmotic pressure which causes
osmosis of fluid inward through capillary membrane
4) ISF colloid osmotic pressure which causes osmosis of fluid
outward through capillary membrane

If the sum of these forces, the net filtration pressure is positive,

there will be a net fluid filtration. If the sum of these is negative,
there is net fluid absorption.
Usually positive to allow net filtration of fluid across capillaries. Also
determined by number and size of pores as well as number of
capillaries
Known as capillary filtration coefficient.
Pumping by lymphatic system is the basic cause of the negative ISF
pressure
Exchange of fluid volume
average capillary pressure at arterial ends of capillaries is 1525 mmHg greater than at venous ends. Because of this, fluid
filters out of capillaries at arterial ends but at their venous
ends, fluid is reabsorbed back into the capillaries. Thus a small
amount of fluid actually flows through the tissues from the
arterial ends of the capillaries to venous ends
net reabsorption pressure at venous ends of capillaries is less
than filtration pressure at the capillary arterial ends but
venous capillaries are more numerous and more permeable
than arterial capillaries so that less reabsorption pressure is
required to cause inward movement of fluid. The reabsorption
pressure causes about 9/10 of the fluid that has filtered out of
the arterial ends of the capillaries to be reabsorbed at the
venous ends. The remaining 1/10 flows into lymph vessels and
returns to circulating blood
Starling equilibrium: under normal conditions a state of near
equilibrium exists at the capillary membrane. That is the amount of
fluid filtering outward from arterial ends of capillaries equals almost
exactly the fluid returned to circulation by absorption. The slight
disequilibrium that occurs accounts for small fluid eventually
returned by lymphatics.
Filtration coefficient: extreme differences in permeability of capillary
systems in different tissues, this coefficient varies more than 100
fold among different tissues. It is very small in both brain and
muscle, moderately large in subcutaneous tissue, large in intestine
and extreme in liver and glomerulus of the kidney where pores are
numerous or open.
When capillary pressure rises too much -> edema
When capillary pressure falls low -> net reabsorption of fluid will
occur -> blood volume increases
Lymphatic system
accessory route through which fluid can flow from ISF into
blood. Carries proteins and large particulate matter away from

tissue spaces, neither of which can be removed by absorption

directly into blood capillaries
everywhere except superficial portions of skin, CNS,
endomysium of muscles and bones but even these tissues
have minute interstitial channels called prelymphatics where
ISF can flow; this fluid eventually empties into lymphatic
vessels or in the case of the brain, into cerebrospinal fluid and
then directly into the blood
eventually all lymph from lower part o body enter thoracic
duct which empties into blood venous system at juncture of
left internal jugular vein and left subclavian vein.
- lymph from left side of head, left arm and parts of chest also
enters thoracic duct before emptying into veins
- lymph from right side of neck and head, the right arm and
right thoracic enters right lymph duct (smaller than thoracic
duct) which empties into blood venous system at juncture of
right subclavian vein and internal jugular vein
terminal lymphatic capillaries and permeability: most fluid
filtering from arterial ends flows among cells and finally is
reabsorbed back into venous ends of blood capillaries but on
average about 1/10 enters lymphatic capillaries and returns
via lymph system. Important with proteins.
Endothelial cells of lymphatic capillaries are attached by
anchoring filaments to surrounding connective tissue. At
junctions of adjacent endothelial cells, edge of one cell
overlaps another so that overlapping edge can flap inward to
form a valve. ISF can push valve open and flow directly but it
has difficulty leaving the capillary because backward flow
closes the flap valve.
Lymph is from ISF so lymph entering terminal lymphatics has
same composition as ISF. About 2/3 of all lymph is derived
from liver and intestines so thoracic duct lymph has about
that concentration. Lymphatic system is also major route for
absorption of nutrients from GIT esp fats. Large particles such
as bacteria can enter lymph and destroyed through passage
into lymph nodes
Any factor that increases ISF pressure also increases lymph
flow if lymph vessels are functioning normally:
- elevated capillary pressure
- decreased plasma colloid osmotic pressure
- increased ISF colloid osmotic pressure
- increased permeability of capillaries
very high pressures: compresses outside surfaces of larger
lymphatics to impede lymph flow (max lymph flow)
valves exist in lymph channels when collecting lymphatic
becomes stretched with fluid, smooth muscle in the wall of
vessel contracts. Furthermore each segment of lymph vessel
between successive valves function as a separate pump. Even

slight filling of a segment causes it to contract and the fluid is

pumped through next valve into the next
as well as intrinsic pumping, extrinsic pumping also occurs:
contraction of surrounding skeletal muscles, movements of
parts of body, pulsations of arteries adjacent to lymphatics,
compression of tissues by objects outside the body
terminal lymphatic capillary is also capable of pumping lymph
in addition to the lymph pumping by larger lymph vessels. As
lymphatic capillaries are adherent to surrounding tissue cells
by anchoring filmlaments, each time excess fluid enters the
tissue and causes swelling, anchoring filaments pull on the
wall of the lymphatic capillary and fluid flows into terminal
lymphatic capillary. Then when tissue is compressed, pressure
inside capillary increases and causes overlapping to cloes the
valve Lymphatic capillary endothelial cells also have
contractile actomyosin filaments. May cause rhythmical
contractions.
lymphatic system central to 1) concentration of proteins in ISF
2) volume of ISF 3) ISF pressure
negative ISF pressure is important to hold body tissues
together. When tissue loses their negative pressure, fluid
accumulates in spaces (edema)