VASCULAR SYSTEM
- THE HEMODYNAMICS -
Lecture 2
Dr. Ana-Maria Zagrean
Microcirculation
• Main function:
-transport of nutrients…
-removal of cellular excreta…
• Arteriols (highly muscular, their diameters can change manyfold)
• Metarteriols/terminal arteriol (do not have a continuous muscular coat, but
smooth muscle fibers encircle the vessel at intermittent points)
• Precapillary sphincters (smooth mm cell, local control of blood flow)
• Capillaries
Microcirculation
Closed
capillaries
An artery branches 6-8 x until becoming
arterioles; these are branching further
2-5 x towards capillaries.
Capillaries
• diameter = 4-9 mm, 10 billions, surface = 500 - 700 m2
Capillary no, distance capill-cells (20-30 µm)~ metabolic activity of the tissue
• “pores” in the capillary membranes:
1. intercellular cleft / gap: 6-7 nm, S~1/1000 of the total capillaries
surface, allow the thermal motion of only small molecules
2. plasmalemmal / transcytosis vesicles = caveolae: role in
endocytosis, transcytosis (coalesce to form vesicular channels/pores)
3. special types of pores:
- large clefts in intestinal membranes, larger in liver capillaries
(endothelial discontinuity...)
- fenestrae in glomerular capillaries (20 to 100 nm), that appear
to be sealed by a thin diaphragm, but they are permeable to larger
molecules
- no pores, but tight junctions, in brain capillaries (BBB)
• permeability is not uniform along the whole capillary:
arterial end < venous end < venules (greater no of pores/clefts)
“Pores” in the capillary membranes
Exchange between blood & interstitial fluid takes place in the
capillaries by diffusion, filtration, pinocytosis (transcytosis).
(leaky junctions)
Cerebral endothelium: Tight-junction epithelium &
blood-brain barrier
Pericytes
• Capillary walls are closely associated with elongated,
highly branched cells = pericytes
• Mesh-like outer layer between endothelium and interstitial
fluid, more developed at the capillary venous end and
venules level
• Functions: exchange, growth & repair processes, local
control of blood flow at microcirculation level
Average function of the capillary system
• For the billions of capillaries which operate intermittently in
response to the local conditions in the tissue, there are…
• average rate of capillary blood flow
• average capillary pressure
• average rate of transfer of substances
Blood flow in the microcirculation
• Vasomotion
= intermittent contraction/relaxation of the metarteriols and
precapillary sphincters (5-10/min)
- partly an intrinsic contractile behavior of the vascular
smooth muscle
-depends on local and humoral factors, mostly on O2 conc.
-influenced by sympathetic tone
Blood flow in the microcirculation
Blood flows intermittently/randomly or it may oscillate rhythmically at
different frequencies as determined by contraction and relaxation
(vasomotion) of the precapillary vessels.
Changes in transmural pressure = intravascular press. ▬ extravasc. press*
affect the contractile state of the precapillary vessels:
increase of transmural pressure  terminal arteriole/precapillary
constriction
 CHANGES IN CAPILLARY DIAMETER ARE PASSIVE AND ARE CAUSED BY
ALTERATIONS IN PRECAPILLARY AND POSTCAPILLARY RESISTANCE.
Average velocity of capillary blood flow ~1 mm/sec (zero-several mm/sec).
*Transmural pressure is essentially equal to intraluminal pressure because
extravascular pressure is usually negligible.
Laplace's law
T = P x r , in which P, intravascular pressure; r, radius of the vessel; T, wall
tension as the force per unit length tangential to the vessel wall (a force that tends
to pull apart a theoretical longitudinal slit in the vessel).
r of resistance vessels ~ contractile force of the vasc. smooth muscle
~ distending force produced by the intraluminal pressure.
Intravascular pressure diminished  vessel diameter and tension in the vessel wall
decreased (Laplace's law) terminal arteriole response: vasodilation
When perfusion pressure is progressively reduced, a value of the transmural pressure
= critical closing pressure is reached; at this pressure the vessel is occluded and
blood flow ceases even though a positive pressure gradient from the afferent to the
efferent end of the vessel may still exist.
Also, small arterioles may be occluded because of infolding of the endothelium.
Consequences of Laplace's law: T=p x r
Even the capillaries are thin-walled, they can withstand high internal
pressures without bursting because of their narrow lumens.
At normal aortic (100 mm Hg) and capillary (25 mm Hg) pressures, the wall
tension of the aorta is about 12,000 times greater than that of the capillary:
100 mmHg × r of 1.5 cm for the aorta vs. 25 mmHg × r of 5×10-4 cm for the capillary
In a person standing quietly, capillary pressure in the feet may reach 100 mm
Hg. Under such conditions, capillary wall tension increases to a value that is
only 0.003 that of the wall tension in the aorta at the same internal pressure.
According to Laplace's equation, wall tension increases as vessels dilate, even
when internal pressure remains constant (T=p x r).
In aneurysm (local widening) of the aorta, the wall tension may become high
enough to rupture the vessel.
Endothelium synthesize substances that affect the
contractile state of the arterioles:
1. Endothelium-derived relaxing factor (EDRF) - nitric oxide (NO),
vasodilator formed and released in response to stimulation of the
endothelium by various agents (e.g., acetylcholine, ATP, serotonin,
bradykinin, histamine, substance P); NO can also interfere with platelet
aggregation.
2. Endothelium-derived hyperpolarizing factor (EDHF) - vasodilator
3. Prostacyclin, a vasodilator that also inhibits platelet adherence to the
endothelium and platelet aggregation, aiding in the prevention of
intravascular thrombosis
4. Endothelin, a 27-am.ac. powerful vasoconstrictor substance, require
just ng for vasoconstr., released in large quantities in lesioned endothelium
5. Also, synthesize structural components: glycocalyx, basal lamina
endoth. enzymes: AG converting enz, carbonic anhydrase (lungs)
thromboxane, von Willebrand factor (f VIII)
adhesive molecules involved in cell migration during inflammation
Endothelium- and nonendothelium-mediated vasodilation
Prostacyclin (PGI2) is formed from arachidonic acid (AA) by the action of cyclooxygenase
(Cyc-Ox) and prostacyclin synthetase (PGI2 Syn) in the endothelium and elicits relaxation of
the adjacent vascular smooth muscle via increases in cAMP.
Stimulation of the endothelial cells with acetylcholine (Ach) results in the formation and
release of an EDRF (NO). EDRF stimulates guanylyl cyclase (G Cyc) to increase cGMP in the
vascular smooth muscle to produce relaxation. The vasodilator agent nitroprusside (NP)
acts directly on the vascular smooth muscle.
Substances such as adenosine, H+, CO2, and K+ can arise in the parenchymal tissue and
elicit vasodilation by direct action on the vascular smooth muscle.
Vasomotion is influenced by sympathetic tone
Arterioles - A, before and B, after the microinjection of norepinephrine.
Right inset - capillary with red cells during a period of complete closure
of the feeding arteriole.
Angiogenesis creates new blood vessels
Relation angiogenesis
– growth, development, wound healing
– endurance exercise training
Angiogenic vs. antiangiogenic factors/cytokines:
mitogens like VEGF, FGF vs. angiostatin and endostatin
Therapeutic role: cancer, coronary artery disease/myocardial
ischemia
Arterial pressure
• Flow in the arterial side of the circulation is pulsatile, reflecting the
changes in arterial pressure throughout a cardiac cycle; once past the
arterioles, pulse waves disappear.
• Systolic pressure (SP): highest during a cardiac cycle, highest in aorta
~ 120 mmHg
• Diastolic pressure (DP): lowest during a cardiac cycle
~ 80 mmHg
! As diastolic pressure in LV ~ 0 mm Hg, DP in large arteries remains
relatively high because of their capacity to store energy in the elastic
walls.
The pressure pulse wave
=
-
a moving wave of pressure that assists the continuous flow…
determined by the ejection of blood in aorta
transmitted through the fluid-filled arteries
10-15x more fast than the blood
its velocity is increasing from aorta (3-5 m/sec) to large arteries (7-10
m/sec), small arteries (15-35 m/sec), along with the decrease in the
vessels compliance
Pulse pressure
Pulse pressure = P systolic – P diastolic =120 - 80= 40 mmHg
= f (stroke vol., low arterial compliance)
Example in aging: ↓ compliance cause ↑ pulse pressure.
Friction effect
Mean arterial pressure
MAP = average arterial pressure with respect to time
- representative for the driving pressure*
= diastolic pressure + 1/3 pulse pressure
MAP = 80 mmHg + 1/3(120-80 mmHg)= 93 mmHg
for HR = 60-80 beats/min
MAP value more close to the DP.
Why?
Diastole lasts twice as long as systole.
What happens with MAP value if HR increases?
SP=112 mm Hg
DP=68 mm Hg
(112/68)
Pulse pressure=?
44
MAP=?
82.6
Arterial pressure is estimated by sphygmomanometry
• AP in brachial artery of the arm
• Sphygmomanometer: inflatable cuff, pressure gauge
When the cuff is inflated so that it stops arterial
blood flow, no sound can be heard through a
stethoscope placed over the brachial artery
distal to the cuff.
Korotkoff sounds are created by pulsatile
blood flow through the compressed artery.
Blood flow is silent when the artery is no
longer compressed.
Exchange of nutrients and other substances
between the blood and interstitial fluid
• Diffusion… back and forth – continual mixing – random
movement
• Diffusion results from thermal motion of water molecules and
dissolved substances
• What diffuses…
– Lipid-soluble substances [through cell membrane]: O2, CO2
– Water-soluble, non-lipid-soluble substances [only through
intercellular pores]: H2O, Na+, Cl-, glucose
– Great velocity of thermal motion  tremendous diffusion
[rate of H2O diffusion through the capillary mb.= 40 ÷ 80 x the rate
at which plasma itself flows linearly along the capillary]
Diffusion depends on lipid-solubility, molecular size / MW,
concentration difference between the two sides of the
membrane...
Arterial
end
Blood
capillary
Venous
end
DIFFUSION
Lymfatic capillary
Diffusion between capillary and interstial fluid
Effect of molecular size on passage
through the pores
dintercell. cleft = 6-7 nm ~ 20 x dwater
< dplasma protein molecules
 interstitial fluid contains almost the same
constituents as plasma except for the proteins
Capillary pores do not restrict the fast diffusion of water,
NaCl, urea or glucose; they pass as much as they are
available in the blood (flow limited transport)
Minimal diffusion of molecules with MW > 60.000 (diffusion
limited transport).
Relative permeability of muscle capillary pores to
different-sized molecules
Substance
Water
NaCl
Urea
Glucose
Sucrose
Inulin
Myoglobin
Hemoglobin
Albumin
MW
18
58,5
60
180
342
5000
17000
68000
69000
Permeability coefficient
1
0,96
0,8
0,6
0,4
0,2
0,03
0,01
0,0001
Reflection coefficient - relative impediment to the passage of a
substance through the capillary membrane
= 0 for water
= 1 for albumin
Filterable solutes have reflection coefficients between 0 and 1.
Net rate of diffusion through the capillary membrane
- net rate of diffusion is proportional to the concentration difference
between the two sides of the membrane
- e.g., concentration difference for O2, CO2
glucose
- O2, CO2 : lipid-soluble, readily pass through the endothelial wall
 possible diffusion shunt of gas around the capillaries, or directly
between adjacent arterioles and venules
 diffusion of O2 from the arterioles can decrease blood O2 content
at this level to about 80% of that in the aorta
Arterial
end
Blood
capillary
Venous
end
Interstitium
Lymfatic capillary
Interstitium:
-solid structures (collagen fiber bundles, proteoglycan [PG] filaments)
-interstitial fluid is derived by filtration and diffusion from the capillaries
-interstitial/tissue “gel”: the interstitial fluid entrapped within the PG filaments
mainly diffuses through the gel (velocity ~ 95%-99% for free fluid flow)
-free fluid vesicles in the interstitium: normally <1%, ↑ ↑ in edema
Arterial
end
Blood
capillary
Venous
end
DIFFUSION
FILTRATION
Lymfatic capillary
Exchanges between capillary and interstial fluid:
capillary filtration is regulated by the hydrostatic and
osmotic forces across the endothelium
Four primary forces determine fluid movement
through the capillary membrane: ‘Starling forces’
(Ernest Starling, 1896)
1.
2.
3.
4.
Capillary pressure (Pc) – hydrostatic pressure which
tends to force fluid outward through the capillary mb.
Interstitial fluid pressure (Pif) – hydrostatic press. in
the interstitial fluid which tends to force fluid
outward(+)/inward(-) through the capillary mb.
Plasma colloid osmotic pressure (Pp) – osmotic
pressure caused by the plasma proteins, which tends to
cause osmosis of fluid inward through the capillary mb.
Interstitial fluid colloid osmotic pressure (Pif) osmotic pressure caused by the proteins in the
interstitium, which tends to cause osmosis of fluid
outward through the capillary mb.
Mean capillary (hydrostatic) pressure
• Mean capillary pressure measurement:
- direct micropipette cannulation of the capillaries: 25mmHg
- indirect functional measurement: 17mmHg
• Mean functional capillary pressure = 17,3 mmHg (nearer to
the pressure in the venous end):
- precapillary sphincters are closed during a large part of the
vasomotion cycle
- venous capillaries are several times as permeable as the
arterial capillaries
- there are far more venous capillaries then arterial ones.
Colloid osmotic pressure
• Only those molecules or ions that fail to pass through the
pores of a semipermeable membrane exert osmotic pressure
• Proteins are the only significant dissolved constituents that do not
readily penetrate the pores of the capillary membrane.
 Dissolved proteins of the plasma and interstitial fluids that are
responsible for the osmotic pressure = colloid osmotic pressure
or oncotic pressure (P).
 Pp = 28 mmHg
19 mmHg from dissolved proteins (80%-albumin, 20%-globulin)
9 mmHg from the cations associated with plasmatic proteins
(Gibbs-Donnan effect)
 Pif = 8mmHg (protein concentration in IF is 40% of that in
plasma, no Donnan effect here)
Qf - fluid movement across the capillary wall
k - filtration constant for the capillary membrane
Pc - capillary hydrostatic pressure (mm Hg)
πi - interstitial fluid oncotic pressure (mm Hg)
Pi - interstitial fluid hydrostatic pressure (mm Hg)
πp - plasma oncotic pressure (mm Hg)
Net filtration occurs when the algebraic sum of the hydrostatic
and osmotic pressures across the capillaries is positive, and
net absorption occurs when the sum is negative.
Starling Equilibrium for Capillary Exchange
Arterial end
Pc=30 mmHg
Pp =28 mmHg
Poutward=13mmHg
Pif = -3 mmHg
Pif = 8 mmHg
Venous end
Pc=17,3mmHg
Pp=28mmHg
Net outward force=0,3
Pif = -3 mmHg
Pif = 8 mmHg
Pc=10 mmHg
Pp=28 mmHg
Pinward=7mmHg
Pif = -3 mmHg
Pif = 8 mmHg
NET FILTRATION=2ml/min/entire body
drained as LYMPH
NET FILTRATION PRESSURE:
outward inward
net outward force
(30+3+8 ) – 28 = 41 – 28 =13 mmHg
NET REABSORBTION PRESSURE:
inward
outward net inward force
28 -(10+3+8 ) =28 – 21= 7 mmHg
Fluid exchange at the capillary
- Quick movement of fluid across the capillary endothelium
- Filtration and absorption occur with very small imbalances of pressure
across the capillary wall.
 only about 2% of the plasma flowing through the vascular
system is filtered, and of this, about 85% is absorbed in the capillaries
and venules. The remainder returns to the vascular system in the lymph,
along with the albumin that escapes from the capillaries.
Lymphatic system
Accessory rout for fluid drainage from
interstitium (1/10 of the filtrated fluid, 2-3L/ day)
together with proteins and macromolecules; act
as an ‘overflow mechanism’; its function is
essential for survival.
Lymphatic vessels in almost all tissues of the
body (exception epidermis, brain, muscles
endomysium and bones; here – minute
interstitial channels = prelymphatics).
Terminal lymphatic vessels - close-end
network of highly permeable lymph capillaries,
anchored through fine filaments to the
surrounding connective tissue
Lymphatic system
Juncture of subclavian
vein and internal
jugular vein
Terminal lymphatic capillaries 
collecting lymphaticlymphatic vessels 
thoracic (left lymph) duct/right lymph duct
Lymphatic system
Special structure of the lymphatic capillaries:
- Endothelial cells (EC) with actomyosin filaments & anchoring
filaments to the surrounding connective tissue (lymphatic capillary
pump)
- the edges of adjacent EC overlap in a minute valve, allowing an
inward flap; the backflow in the lymphatic capillary closes the flap
valves.
Structure of lymphatic vessels:
- valves along lymphatic vessels up to the point where they
empty into the blood circulation;
- smooth muscle that contracts in response to stretch
 system of pumps & valves (lymphatic pump)
Lymphatic capillary
Lymph composition
- almost the same as interstitial fluid
- proteins: 2 g/L in lymphatic capillaries
6 g/L in liver lymphatics
3-4 g/L in intestines lymphatics
-
2/3
3-5 g/L in thoracic duct
nutrients from GIT (1-2% fats after a fatty meal)
lipid-soluble vitamins (A, D, E, K)
lymphocytes
globulins synthesized in lymphatic nodes
clotting factors
microorganisms
Lymph flow
- 2 mL/min = 120 mL/hour = 2-3 L/day
- Interstitial fluid pressure
Lymph flow
< (-6) mmHg
minim
(-2) ÷ 0 mm Hg
maxim (20 fold increase)
>1,5 ÷ 2 mm Hg
maxim, constant
- Factors that increase lymph flow:
- intrinsic: ↑Pc, ↓Pp, ↑ Pif, ↑ permeability of the capillaries,
lymphatic pump (valves & smooth mm.)
- extrinsic: skeletal mm contraction, body movements,
pulsations of arteries adjacent to the lymphatics,
external compression of the tissues
- Lymph flow increase 10- to 30-fold during exercise and
decrease to almost zero during periods of rest
Roles of the lymphatic system
1.
2.
3.
4.
Control the concentration of proteins in IF (prevent the
increase in Pif); return the ‘filtered’ proteins to the
blood;
Control the volume of IF;
Control the pressure of IF (favours the fluid filtration
into the interstitium and maintenance of lymph flow).
Lymph nodes filter the lymph and removes foreign
particles such as bacteria
The Venous System
Functions of the Venous System
- Circulatory function:
-blood return to the heart;
-constriction/enlargement, storing/making available
the blood when required,
-regulate cardiac output through venous return,
venous pump (peripheral veins)
- Blood reservoir: 64% from total blood volume
Blood flow through the venous system
Blood flow converges in the venules and veins:
Smallest venules:
-similar to capillaries
-thin exchange endothelium, little connective tissue
- show a convergent pattern of flow
Larger venules:
-contain also smooth muscle
-drain blood into larger veins
Veins:
-diameter, volume …(hold more then 50% of the blood),
-less elastic, more distensible tissue
-lie closer to the surface of the body; venipuncture
-below the heart there are veins with internal one-way valves
-drain blood into venae cave  RA (central venous pressure)
Venous valves of the leg
Blood flow through the venous system
Valves create one-way flow in the veins below the heart
Chronic excess venous press.  venous valve incompetence varicose veins
Venous Pressures
Central venous pressure (CVP): Right atrial pressure
Peripheral venous pressure
Right atrial pressure - central venous pressure (CVP)
- zero pressure reference level: tricuspid valve in a person standing/laying
down, at which gravitational pressure factors caused by changes in body
position usually do not affect the pressure measurement by more than 1-2
mmHg
- CVP depends on:
1) ability of right heart to pump: normally, maintains a decreased CVP, favoring
the venous return
2) venous return of the blood from the peripheral veins into the right atrium,
directly depends on:
- blood volume,
- large vessel tone/peripheral venous pressures,
- arterioles tone: their dilation decreases the peripheral resistance
and allows rapid flow of blood from the arteries into the veins.
- RA press.: normal ~ 0 mmHg = atmospheric press. around the body
increases ~ 20÷30 mmHg under abnormal conditions (heart failure,
massive blood transfusion, which increases blood volume/venous return).
decreases up to -3÷-5 mmHg below atm. press.
~ intrathoracic pressure
- when heart pumps with exceptional vigor
blood volume decreases/severe hemorrhage.
Venous pressure in periphery
Resistance to blood flow when large veins are distended is almost zero.
Large veins that enter the thorax and the large abdominal veins are compressed
at different points by the surrounding tissues  blood flow impeded at these
points  small increase in resistance to blood flow at this level  pressure in the
more peripheral small veins in a person lying down is usually +4 to +6 mmHg
greater than CVP.
Compression points between peripheral veins and large central veins:
- Rib collapse: in the arm veins, the pressure at the level of the first rib is usually
about +6 mmHg because of compression of the subclavian vein as it passes in
sharp angulation over this rib.
-Atmospheric press. collapse: neck veins of a person standing upright collapse
almost completely because of atmospheric pressure on the outside of the neck 
pressure in these veins remains at zero; also, any press. increase will increase
blood flow, any press. decrease will rise the resistance
- Abdominal pressure collapse: abdominal veins are often compressed by
different organs and by the intra-abdominal pressure (+6 mmHg15-30 mmHg).
Compression points that tend to collapse the veins entering the thorax.
Peripheral venous pressure depends on:
RA pressure:
- >0 mmHgblood begins to back up in the large veins veins enlargement
- rise at +4 to +6 mmHg (e.g., during heart failure) opening of the veins
at the collapse points
- >+6 mmHg  rise in peripheral venous press. in the limbs and elsewhere.
Intra-abdominal pressure:
- normally up to +6 mm Hg,
- can rise to +15 to +30 mmHg (pregnancy, large tumors, excessive fluid in
the abdominal cavity/ascites) drainage of the blood from the legs only
when the pressure in the veins rise above the abdominal pressure (e.g., if
the intra-abdominal pressure is +20 mm Hg, the lowest possible pressure in
the femoral veins is also +20 mm Hg).
Gravitational/hydrostatic pressure
-occurs in the vascular system because of weight of the blood in the vessels
- ! Also affects arterial pressure in the peripheral arteries and capillaries.
In a standing person, for a MAP of 100 mmHg at the level of the heart, the
arterial press in the feet is about 190 mmHg…
Gravitational/hydrostatic pressure
Gravitational/hydrostatic pressure occurs in the vascular system because of
weight of the blood in the vessels (1 mmHg for each 13.6 millimeters).
For a standing person:
•pressure in the RA remains ~ 0 mmHg (heart pumps any excess blood)
•pressure in the veins of the feet
~+90 mmHg if standing still at least 30 sec.,
<+20 mmHg if walking (venous/muscular pump)
• pressure between 0-90 mmHg at other levels of the body:
+40 mmHg in the femoral a., +35 mmHg in the hands (+6+29...)
-10 mmHg in the sagittal sinus (hydrostatic ‘suction’ between the
top and the base of the noncollapsible skull cavity; risk of air
embolism if sagittal sinus is opened during surgery).
• after standing still for 15 – 30 min., blood volume decreases with 10-20%
(fluid leakage, legs swell...)
Effect of Gravitational Pressure on Venous Pressure
Clinical estimation of venous pressure.
-observing the degree of distention of the peripheral veins (neck veins): in
sitting position, the neck veins are never distended in the normal quietly
resting person, but distend when the RA pressure > +10 mm Hg.
Direct measurement of venous pressure and RA pressure (CVP)
-by inserting a catheter through the peripheral veins and into the right
atrium (central venous catheter) to assess the heart pumping ability.
Reference point for circulatory pressure measurement
(located at/near the tricuspid valve).
Factors involved in venous return
1. Pressure gradient
• Central venous pressure: RA pressure
• Venous pressure in periphery:
2. Hydrostatic/gravitational pressure (1 mmHg for 13.6 mm)
• Body position
• Standing person: standing still or walking...
3. Heart activity:
• Aspiration pump together with the venous pump/muscle pump