The Circulation - Fiziologie 13 Circ2.pdf · Capillaries –inner radius 2 - 5 mm Single layer of...
Transcript of The Circulation - Fiziologie 13 Circ2.pdf · Capillaries –inner radius 2 - 5 mm Single layer of...
Adelina Vlad, MD Ph
The Circulation- part 2 -
Physical Characteristics of the
Vascular System
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
Distribution
of blood
Aggregate Cross-Sectional
Area (cm2)
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
Normal blood pressures in the different portions of the circulatory
system when a person is lying in the horizontal position
Pulsatile
Mean value:
100 mmHg
Average
pressure
17 mm Hg
0 mm
Hg
LV
Pulsatile
Mean value:
16 mmHg
Average
pressure
7 mm Hg
RV
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
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
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”
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) the interstitial fluid pressure
2) 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 CapillariesBased 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 Forces1) 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
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
DP DPArterial end
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*
Pa (mm Hg) Pc (mm Hg) Pv (mm Hg)
Control 60 25 15
Increased arteriolar
pressure
70 27 15
Increased venular
pressure
60 33 25
*Constant Rpost/Rpre= 0.3.
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)
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
Acute Control
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
The vascular endothelium is the source of several important
vasoactive compounds
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
Endothelial Factors
VASODILATORS VASOCONSTRICTORS
Nitric oxide (NO) Endothelin (ET)
Endothelium-derived
hyperpolarizing factor (EDHF)
Endothelium-derived
constricting factor-1 (EDCF1)
Prostacyclin (PGI2) Endothelium-derived
constricting factor-2 (EDCF2)
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)
PROMOTERS INHIBITORS
Vascular endothelial
growth factor (VEGF)
Endostatin
Fibroblast growth factors
(FGFs)
Angiostatin
Angiopoietin-1 (ANGPT1) Angiopoietin-2 (ANGPT2)
AGENTS THAT AFFECT VASCULAR GROWTH