The Circulation
- part 2 Adelina Vlad, MD Ph
Physical Characteristics of the
Vascular System
Aggregate Cross-Sectional
Area (cm2)
Distribution
of blood
Mean linear velocity of blood flow
is inversely proportional to
aggregate vascular cross-sectional
area:
- 21 cm/s in the aorta
- 0.03 cm/s in the capillaries,
under resting conditions
- 14 cm/s in venae cavae
Pressures Along the Vascular System
 High pressure zone: contracting LV  systemic arterioles
 Low pressure zone: systemic capillaries  right heart 
pulmonary circulation  left atrium LV in relaxed state
Average
pressure
17 mm Hg
LV
Pulsatile
Mean value:
100 mmHg
Average
pressure
7 mm Hg
0 mm
Hg
Pulsatile
Mean value:
16 mmHg
RV
Normal blood pressures in the different portions of the circulatory
system when a person is lying in the horizontal position
Structure – Function Relationship
(elastic fibers
dominance)
(collagen fibers
dominance)
Systemic Veins
 Allow blood return to the heart
 By contracting or enlarging their lumen, veins can
 adjust the amount of blood returned to the heart and influence
the cardiac output (Frank-Starling mechanism)
 store or mobilize large amounts of blood in accordance to
the physiologic needs
 Veins are compliant structures, with low resistance and large
capacitance  they can accommodate important amounts of
blood for a tiny increase in pressure
 Total cross-section area of veins is larger than similar degrees of
arborisation in the arterial system, therefore blood advances with
a much lower velocity through the veins
 Pressure in the venous bed decreases from periphery
towards atria, generating a pressure gradient that allows blood
to return from tissues to the heart
 venous return is favored by an increase of pressure in the
periphery and a lowering of pressure on the way to the heart
Central Venous Pressure
 = The pressure in the right atrium, the endpoint of systemic
venous return
 It is regulated by a balance between
 the ability of the heart to pump blood out of the right atrium
and ventricle into the lungs
 the tendency for blood to flow from the peripheral veins into
the right atrium
Central Venous Pressure
 Normal value: about 0 mm Hg;
 Can increase to 20 - 30 mm Hg due to
 serious heart failure
 massive transfusion
 Can decrease to about -3 - -5 mm Hg, which is the pressure in
the chest cavity that surrounds the heart
 when the heart pumps with exceptional vigor
 when blood flow from the peripheral vessels to the heart is
greatly depressed (severe hemorrhage)
 Peripheral venous pressure is
increased by:
 raise of RA pressure above +4 to
+6 mm Hg (heart failure)  blood
begins to back up into the veins
 high intra-abdominal pressure
(pregnancy, abdominal tumors,
ascites)  pressure in the legs
veins must surpass intra-abdominal
pressure
 hydrostatic pressure when there
is a difference in height along the
veins
 Venous resistance
 Could be very low
 Large veins do usually offer some
resistance to blood flow due to
compression by the surrounding
tissues:
 veins from the arms over the first rib
 intra-abdominal veins by different
organs and by the intra-abdominal
pressure
 neck veins often collapse under the
push of the atmospheric pressure
Venous return can be increased by:
 Increased blood volume
 Decreased pressure toward the heart
 During inspiration
 By low pressures in the right atrium provided by a good RV
performance
 Increased pheripheral venous pressure:
 increased large vessel tone throughout the body with resultant
increased peripheral venous pressures
 dilatation of the arterioles which decreases the peripheral
resistance and allows rapid flow of blood from the arteries into
the veins
 The activity of the “venous pump”
 Changing body position from standing/sitting to horizontal or by
rising the legs while lying down
Venous Valves and the Venous Pump
 Veins below the heart level are equipped with valves that allow
blood to flow in only one direction – towards the RA
 When veins below the heart are compressed by contracting
muscles or pulsing arteries, due to the valves inside the veins
the blood is pushed forward to the RA = “venous pump” or
“muscle pump”
 the venous pressure in the feet
of a walking adult is less than
+20 mm Hg, whereas in the
standing, immobile position it
would be + 90 mm Hg
 Venous valve incompetence
causes varicose veins
Estimation of Venous Pressure
 Clinical estimation - by simply observing the degree of
distention of the peripheral veins: external jugular veins begin to
protrude at + 10 mm Hg RA pressure
 Direct measurement of
 Peripheral venous pressure – with a needle connected to a pressure
recorder
 RA pressure – with central venous catheters
 Zero height pressure reference
level
- near the level of the tricuspid valve
- here the pressure is unaffected by
changes of body posture because
the heart acts as a feedback
regulator of pressure
Reservoir Function of the Veins
 More than 60% of all the blood in the circulatory system is
usually in the veins
 When circulating blood volume decreases, nervous reflexes
determine the mobilization of blood from the reservoirs of the
body  venous reservoir can cover a loss of up to 20% of the
total blood volume
 Specific blood reservoirs
 the venous sinuses of the spleen, 100 ml
 the venous sinuses of the liver, several hundreds ml
 the large abdominal veins, 300 ml
 the venous plexus beneath the skin, several hundreds ml
Limphatic System
Limphatic System
 Filtration at the arteriolar end of the
capillary exceeds reabsorbtion at the
venular end by 2 – 3 l/day  this
excess liquid together with proteins
and other large molecules from the
interstitium move into the lymphatics
 Limphatics – arise at the interstitium as
small thin-walled channels  larger
vessels  the thoracic duct and the
right lymph duct  drain into the left
and right subclavian veins
 Limphatics are absent from some
tissues (myocardium, brain, bones...)
Structure of Limphatic Vessels
 Capillaries
- closed ended channels with endothelial cells that are attached
by anchoring filaments to the surrounding connective tissue
- at the junctions of adjacent endothelial cells, the edge of one
endothelial cell overlaps the edge of the adjacent cell forming a
minute valve that opens to the interior of the lymphatic capillary
 Larger lymphatic vessels – have walls similar to those of small
veins (endothelium, smooth muscle)
 Lymphatic vessels are equipped with valves
Formation of Lymph
 Lymph as it first enters the terminal lymphatics has almost the
same composition as the interstitial fluid; protein concentration of
about 2 g/dl in most tissues, 6 g/dl in liver and 3-4 g/dl in
intestines  3-5 g proteins/dl in the thoracic duct lymph
 Lymphatic system is also one of the major routes for absorption
of nutrients from the gastrointestinal tract, especially for virtually
all fats in food – up to 1-2% fat in the thoracic duct lymph after a
fatty meal
 Large particles such as bacteria can enter the lymph, but they
are removed and destroyed as the lymph passes through the
lymph nodes
Rate of Lymph Flow
 Averages 120 ml/hr or 2 to 3 liters per day
 Two primary factors determine lymph flow
1)
2)
the interstitial fluid pressure
the activity of the lymphatic pump
The interstitial fluid pressure
 Increased interstitial fluid pressure increases lymph flow
 But only up to the “maximum
lymph flow rate” (plateau) – when
the interstitial fluid pressure
becomes greater than atmospheric
pressure (0 mm Hg), the
increasing tissue pressure also
compresses the outside surfaces
of the larger lymphatics, impeding
lymph flow
Lymphatic Pump
 Intrinsic pump
 When a collecting lymphatic or larger lymph vessel becomes
stretched with fluid, the smooth muscle in the wall of the
vessel automatically contracts
 Each segment of the lymph vessel between successive valves
functions as a separate automatic pump
 In the thoracic duct, this lymphatic pump can generate
pressures as great as 50 to100 mm Hg
 External intermittent compression of the lymphatics
 Contraction of surrounding skeletal muscles and intestines
 Movement of the parts of the body
 Pulsations of arteries adjacent to the lymphatics
 Compression of the tissues by objects outside the body
 Lymphatic capillary pump
 Terminal lymphatic capillaries are tethered to surrounding
connective tissue by means of the anchoring filaments 
muscle contraction or swelled interstitium can deform them,
making the openings between the endothelial cells more
patent
 The lymphatic capillary endothelial cells also contain a few
contractile actomyosin filaments
Roles of the Lymphatic System
 The lymphatic system plays a central role in controlling
1)
the concentration of proteins in the interstitial fluids
2)
the volume of interstitial fluid
3)
the interstitial fluid pressure
 All these factors are linked to one another:
Proteins leak from the capillaries into the interstitium 
increased interstitial colloid osmotic pressure  increased
volume of interstitial fluid  increased interstitial fluid pressure
 increased limph flow  wash-out of interstitial protein and
liquid in excess
= the return of protein and fluid by way of the lymphatic system
balances exactly the rate of leakage of these into the interstitium
from the blood capillaries = steady state
The Microcirculation
The Microcirculation
 Is the site of the most purposeful function of the circulation:
delivery of nutrients to the tissues and removal of cell excreta
 Is defined as the blood vessels from the first-order arterioles to
the first-order venule
 Principal components: 1 arteriole – metarteriole (+/-) – network of
capillaries – 1 venule
Structural Particulars
 Arterioles – inner radius 5 - 25 mm
 Inner layer of endothelium
 Internal elastic lamina
 A single continuous layer of innervated VSMCs
 Metarterioles – shorter than arterioles
 Similar structure to the arterioles except the VSCMs layer that is
discontinuous and usually not innervated
 Precapillary sphincter – small cuff of VSMCs, usually not
innervated but very responsive to local stimuli
 Capillaries – inner radius 2 - 5 mm
 Single layer of endothelial cells
 Basement membrane
 Pericytes in some tissues – elongated, branched cells involved in
exchange, growth and repair processes, local control of blood flow
 Venules – inner radius 5 - 25 mm
 VSCMs layer is discontinuous, innervated
 May exchange some solutes across their wall
Metarteriolar Shunt
The Capillaries
 The walls of the capillaries are extremely thin and highly
permeable
 The peripheral circulation of the whole body has about 10 billion
capillaries with a total surface area estimated to be 500 to 700
square meters
 The capillaries are the principal site for exchange of
 respiratory gases
 water
 nutrients
 waste products
 Non-nutritional functions of the capillary flow: plasma
filtration in the glomeruli of the kidney, temperature regulation
in the skin, signalling (delivery of hormones) etc.
Endothelial Cells
 Have a smooth surface and are very thin (200 – 300 nm)
 The cytoplasm is rich in endocytotic (pinocytotic) vesicles that
sometimes form a transendothelial channel  transcytosis of
water and water-soluble compounds
 Some have fenestrations – cylindrical conduits through the cell
 Separated by intercellular clefts (10 – 4 nm wide)
 May be linked to one another by tight junctions
 May present gaps 100 – 1000 nm wide between adjacent cells
Vesicles, transendothelial channels,
fenestrae, clefts and gaps are part
of permeation across the
endothelial cells
Types of Capillaries
Based on their degree of leakiness, the capillaries can be
 Continuous capillary - the most common form of capillary; it
has inter-endothelial junctions 10 - 15 nm wide
In the blood-brain barrier - capillaries without clefts and narrow
tight junctions; they don’t permit any paracelullar flow of
hydrophilic solutes
 Fenestrated capillary - the endothelial cells are thin and
perforated with fenestrations
Most often they surround epithelia (e.g., small intestine, exocrine
glands) and are present in the glomerular tufts of the kidney
 Discontinuous capillary - in addition to fenestrae, these
capillaries have large gaps
- found in sinusoids (e.g., liver)
Flow of Blood in the Capillaries
 Is intermittent, turning on and off every few seconds or minutes
due to vasomotion = intermitent contraction of the metarterioles
and precapillary sphincters
 It is influenced mainly by O2 concentration in the surrounding
interstitium
 The parameters of capillary circulation are expressed as average
of the overall capillary activity in each capillary bed:
 average rate of blood flow
 average capillary pressure
 average rate of transfer of substances between the blood of
the capillaries and the surrounding interstitial fluid
Capillary Exchange of Solutes
 The main mechanism for the transfer of solutes across
capillaries is diffusion
 It is governed by:
 specific capillary permeability
 concentration gradient between capillary and interstitium for
each solute
 Fick’s law:
PX = DX/a, the permeability coefficient (cm/s), expresses the ease
with which the solute crosses a capillary by diffusion
 Lipophilic solutes (O2, CO2)
 can permeate all areas of the capillary membrane
 much faster rates of transport through the capillary
membrane than the rates for hydrophilic solutes
 Hydrophilic solutes need special pathways for passing through
the capillary wall
 Paracellular pathway - diffusion through water-filled pores
(clefts, gaps, fenestrae)
 Transcytosis - endocytotic vesicles and transendothelial
channels
Paracellular Pathway
 Hydrophilic solutes smaller than albumin can traverse the
capillary wall by diffusion via a paracellular route: clefts, gaps,
fenestrae
 Diffusion through water-filled capillary “pores” depends on the
 Size of the polar molecules: permeability coefficient PX falls as
the molecular radius increases
 Location: PX increases towards the venular end of the
capillary, where the clefts are wider and the fenestrae are
more common than at its arteriolar end
 Electrical charge of small proteins or other macromolecules,
a major determinant of their PX: negative charges in the
diffusion path favor the transit of molecules with positive
charge and impairs the passage of those with negative charge
 Solvent drag – a dissolved solute can be carried by the
convective movement of water; has a minor contribution
Transcytosis
 Is a second mechanism of macromolecular translocation through
capillary, by means of
 endocytotic (pinocytotic) vesicles
 transendothelial channels formed by the endothelial cells
 Characteristics:
 It’s not governed by the laws of diffusion
 Falls steeply with increases in molecular radius due to steric
hindrance, a process called sieving
 Some of the macromolecular cargo may be processed during
transcytosis (e.g., only a tiny part of the endocytosed ferritin is
delivered to the opposite side of the cell)
 It’s less prominent in brain capillaries  lower permeability of
the blood-brain barrier for macromolecules
Interstitium
 Spaces between cells are collectively called the interstitium
 Interstitium contains two major types of solid structures:
collagen fiber bundles and proteoglycan filaments (98%
hyaluronic acid and 2% protein)
 The interstitial fluid is derived by
filtration and diffusion from the
capillaries  the same components
as plasma but with much lower
concentrations of proteins
 Most of it is entrapped within
proteoglycan filaments  tissue gel;
diffusion through the gel occurs about
95 – 99% as rapidly as it does through
free fluid
 Occasionally a tiny part is free (< 1%)
 free fluid rivulets and vesicles
Capillary Exchange of Water
 The pathways for fluid movement across capillary walls are both
paracellular (clefts, fenestrae, gaps) and transcellular
(aquaporin1 water channels)
 The main mechanism for fluid transfer across capillaries is
convection (bulk water movement) and depends on hydrostatic
and osmotic forces = Starling forces (1856)
Starling Forces
1)
The capillary hydrostatic pressure (Pc) forces fluid outside
the capillary
2)
The interstitial fluid hydrostatic pressure (Pif) forces fluid
outside the interstitium when is positive and attracts fluid into
interstitium when is negative
3)
The capillary plasma colloid osmotic pressure (Pp)
caused by plasma proteins, keeps water inside the
capillaries
4)
The interstitial fluid colloid osmotic pressure (Pif)
caused by interstitial protein and proteoglycans, keeps water
into interstitium
The Net Filtration Pressure
 NFP, is the algebraic sum of
hydrostatic and colloid osmotic
forces acting across the capillary
wall
Arterial end
DP
DP
 If the NFP is positive  net fluid
outflow from the capillaries into
the interstitium = filtration
 If the NFP is negative  net fluid
absorption from the interstitial
spaces into the capillaries
Capillary Filtration Coefficient
 The rate of fluid filtration in a tissue is also determined by the
number and size of the pores in each capillary as well as the
number of capillaries in which blood is flowing
 the capacity of the capillary membranes to filter water for a given
NFP is expressed as the capillary filtration coefficient (Kf) or
hydraulic conductivity; unit measure: ml/min per mm Hg net
filtration pressure
 The rate of capillary fluid filtration is therefore determined as
Filtration = the volume flow of fluid across the capillary wall
Capillary Hydrostatic Pressure
 In the human skin Pc falls from 30 mm Hg at the arteriolar end to
10 mm Hg at the venular end of the capillary
 Pc depends on
 Precapillary resistance (Rpre) and postcapillary resistance




(Rpost): usually Rpre > Rpost
 midcapillary pressure is not the mean value between arteriolar and
venular pressures
Arteriolar and venular pressures: Rpre > Rpost  Pc follows
venular pressure Pv more closely than arteriolar pressure Pa
Location: high Pc in the glomerular capillaries of the kidney, retinal
capillaries; low Pc in the pulmonary capillaries
Time: the permanent fluctuation of the arteriolar diameter and tone of
the precapillary sphincter lead to times of net filtration and other times
of net absorbtion in individual capillaries
Gravity: capillary beds bellow the level of the heart have a higher Pc
than those above the level of the heart
EFFECT OF UPSTREAM AND DOWNSTREAM PRESSURE
CHANGES ON CAPILLARY PRESSURE*
Control
Increased arteriolar
pressure
Increased venular
pressure
*Constant Rpost/Rpre= 0.3.
Pa (mm Hg)
60
Pc (mm Hg)
25
Pv (mm Hg)
15
70
27
15
60
33
25
Interstitial-Fluid Pressure
 Pif is sub-atmospheric (slightly negative) in loose tissues,
averaging about - 3 mm Hg
 Pif is positive in encapsulated organs (kidney, muscle, eye etc.)
and inside rigid enclosed compartments (bone marrow, brain);
however, Pif in the parenchima is lower than pressures exerted
by their encasements (kidney: capsular pressure = +13 mm Hg,
Pif = + 6 mm Hg)
 the normal interstitial fluid pressure is several mm Hg
negative with respect to the pressure that surrounds each
tissue (capsular pressure, barometric pressure)
 The negative Pif is due to fluid removal by the lymphatic pump
Capillary Coloid Osmotic Pressure
 Molecules or ions that fail to pass through the pores of a
semipermeable membrane exert osmotic pressure; water is
attracted towards the compartment with a higher concentration of
osmotic-active particles (and lower “water concentration”)
 Proteins of the plasma and interstitial fluids do not readily pass
through the capillary pores  they are responsible for the
osmotic pressures on the two sides of the capillary membrane =
colloid osmotic or oncotic pressures
 Pp averages about 28 mm Hg
 19 mm of this is caused by molecular effects of the dissolved protein
and
 9 mm by the Donnan effect - that is, extra osmotic pressure caused
by sodium, potassium, and the other cations held in the plasma by
the electro-negatively charged proteins
Types of Plasma Proteins and Pp
 Osmotic pressure is determined by the number of molecules
dissolved in a fluid  small proteins develop a higher P
 albumin is the most important protein for the capillary and
tissue fluid dynamics
Interstitial Fluid Colloid Osmotic
Pressure
 Small amounts of proteins do leak through the capillary wall into
the interstitium (100 – 200 g/day); most of them are removed by
the lymph (95 – 195 g/day); a tiny part is reabsorbed at the
venular end of the capillary (5 g/day)
 Protein leakage varies greatly from tissue to tissue (higher in the
liver: 4 to 6 g/dl, or intestines: 3 to 4 g/dl); the average Pif is
about + 8 mm Hg
 Pif increases along the axis of the capillary because
 protein - free fluid is filtered at the arteriolar end of the
capillary, decreasing protein concentration in the interstitium
(lower Pif)
 protein-free fluid is reabsorbed at the venular end from the
interstitium, increasing protein concentration in the interstitium
(higher Pif)
Fluid Filtration at the Arterial End
of the Capillary
Fluid Reabsorption at the Venular
End of the Capillary
Net Filtration Pressure Along a
Capillary
DP
DP
Starling Equilibrium for Capillary
Exchange
 The amount of fluid filtering outward from the arterial ends of
capillaries equals almost exactly the fluid returned to the
circulation by absorption
 The slight excess of filtration is called net filtration and it is the
fluid that must be returned to the circulation through the
lymphatics (2 ml/min for the entire body)
Interstitial Edema
 Edema (from the Greek oidema, for "swelling") is characterized
by an excess of salt and water in the extracellular space,
particularly in the interstitium
 Occurs due to alteration in
 Hydrostatic forces (high Pc due to immobile upright position,
varicose veins, pulmonary hypertension, right heart inssuficiency etc.)
 Coloid osmotic forces (low plasma protein in nephrotic syndrome,
pregnancy, protein malnutrition, liver disease etc.)
 Properties of the capillary wall (increased permeability due to
inflammation, breakdown of the tight endothelial barrier of the
cerebral vessels, ischemia – reperfusion etc.)
 Lymphatic drainage (removal of lymph nodes for cancer surgery,
lymph nodes obstructed by malignancy, external compression of
limph vessels etc.)
Regulation of the Microcirculation
 Each tissue controls its own local blood flow in proportion to its
metabolic needs
 Tissue metabolites regulate local blood flow in specific vascular
beds independently of the systemic circulation regulation
 Can be:
 Short-termed (acute control)
 rapid changes in local vasodilation or vasoconstriction of
the arterioles, metarterioles, and precapillary sphincters
 Long-termed
 slow changes in flow over a period of days, weeks, months
 increase or decrease in the physical sizes and numbers of
tissue blood vessels (angiogenesis)
Acute Control
 Depends on local mechanisms mediated by
 metabolic factors
 endothelial factors
 autoregulatory processes
 The cardiac output is distributed among tissues in accordance to
their instantaneous needs  the work of the heart is spared by an
optimized distribution of the blood flow
Blood Flow to Different Organs and Tissues Under Basal Conditions
 During heavy exercise, muscle metabolic activity can increase more than 60-
fold and the blood flow as much as 20-fold (15,000 ml/min or 80
ml/min/100 g of muscle)
Role of Resistance in Precapillary
Vessels
 Modulating the contractility of VSMCs in precapillary vessels
is the main mechanism for adjusting capillary blood flow
 Capillary flow is roughly inversely proportional to Rpre because
the aggregate Rcap is small, Rpost/Rpre ≈ 0.3 Rpre > Rcap+ Rpost
 Rpre is the principal determinant of the overall resistance
of the microcirculatory bed (Rtotal)
 Rpre is determined by smooth-muscle tone in arterioles,
metarterioles, and pre-capillary sphincters (R = 8hl /pr4)
Metabolic Control
 There are two basic theories for the regulation of local blood flow
when either the rate of tissue metabolism changes or the
availability of oxygen changes:
 Vasodilator theory
 Oxygen and nutrients lack theory
Vasodilator Theory
 The greater the rate of metabolism, the greater the rate of
formation of vasodilator substances in the tissue cells
 Chemical factors act directly on the VSMCs
LOCAL METABOLIC CHANGES THAT CAUSE
VASODILATION IN THE SYSTEMIC CIRCULATION
CHANGE
MECHANISM
↓ PO2
↓ [ATP]i, adenosine release
↑ PCO2
↓ pHo
↓ pH
↓ pHo
↑ [lactic acid]o
↓ pHo
↓ [ATP]i
Opens KATP channels
↑ [Adenosine]o
Activates purinergic receptors
 Adenosine
 Formed by degradation of adenine nucleotides when ATP
consumption exceeds cell capacity to resynthesize high
energy phosphate compounds, due to
- increased local metabolism
- insufficient local blood flow
- fall in blood pO2
From tissue cells adenosine diffuses into VSMCs  activates
adenosine receptors  K channels open  hyperpolarization 
voltage-gated Ca++ channels close  decreases [Ca2+]i 
vasodilatation  increased O2 supply
Oxygen Lack Theory
 In the absence of adequate oxygen and possibly of some other
nutrients (glucose, thiamine, niacin, riboflavin) blood vessels
simply relax and naturally dilate  oxygen and nutrients supply
raises  vasoconstriction  periodic fluctuation of capillary
blood fow (vasomotion) regulated by the level of oxygen and
nutrients
Acute local feedback
control of blood flow
Endothelial Factors
 The vascular endothelium is the source of several important
vasoactive compounds
VASODILATORS
VASOCONSTRICTORS
Nitric oxide (NO)
Endothelin (ET)
Endothelium-derived
Endothelium-derived
hyperpolarizing factor (EDHF) constricting factor-1 (EDCF1)
Prostacyclin (PGI2)
Endothelium-derived
constricting factor-2 (EDCF2)
 Vasodilators release – stimulated by shear-stress or in response to
acetylcholine
 NO – acts through a cGMP – PKG pathway to decrease the
interaction between actin and myosin (decreases MLC
phosphorilation) as well as [Ca2+]i (SERCA activation)
 EDHF – makes the membrane potential more negative
 Vasoconstrictors release: endothelins (ETs) – long lasting and
potent effect; increases [Ca2+]i
Autoregulation
 Despite large changes in arterial blood pressure the local blood
flow is maintained within a narrow range
 In the physiological pressure range over which autoregulation
occurs (70 – 175 mm Hg), increases in pressure lead to
increases in resistance (flow is maintained approx. constant)
 Autoregulation is an autonomous process
 Realized through myogenic and metabolic mechanisms
Autoregulation
 Myogenic control: the stretch of VSMCs induced by increased
perfusion pressure triggers myogenic contraction (via membrane
stretch receptors and increased Ca++ inflow)
 Metabolic control: the increase in PO2 (or decrease in PCO2, or
increase in pH) that follows an increase in perfusion pressure
triggers a metabolic vasoconstriction that brings the perfusion
pressure back to lower levels
 Importance
 With an increase in perfusion pressure, autoregulation avoids
a waste of perfusion in organs with an already sufficient flow
 With a decrease in perfusion pressure, autoregulation
maintains capillary flow and capillary pressure
 very important for organs sensible to ischemia (heart,
brain) or for organs that filter the blood (kidneys)
Long-Term Control
 In adults the size and shape of microcirculation remains rather
constant
 Exceptions: wound healing, inflammation, tumor growth,
endometrial vessels during the menstrual cycle, physical training,
acclimatization to altitude
 Sustained hypoxia is followed by the expansion of the vascular
bed by angiogenesis (= development of new vessels) and by
arteriogenesis (= development of collateral circulation)
AGENTS THAT AFFECT VASCULAR GROWTH
PROMOTERS
INHIBITORS
Vascular endothelial
growth factor (VEGF)
Endostatin
Fibroblast growth factors
(FGFs)
Angiostatin
Angiopoietin-1 (ANGPT1)
Angiopoietin-2 (ANGPT2)