2. THE FUNDAMENTAL PRINCIPLES OF CIRCULATION IS
THE ABILITY OF EACH TISSUE TO CONTROL ITS OWN
BLOOD FLOW IN PROPORTION TO ITS METABOLIC
NEED.
• And there is variation in blood flow in different tissue
and organs.
• Compared to resting condition, blood flow of exercising
muscle increases up to 20-fold (16000ml/ min) (Laughlin
et al. 1996, Boushel et al. 2000).
• But this matching of demand and supply is impaired in
many vascular disease such as HTN (Bertoldi et al.
2008) DM (Frisbee and Delp 2006, Xiang et al. 2006,
Lalande et al,2007).
• Control of local blood flow by local tissue is important
because tissue never suffer from oxygen nutritional
deficiency and work load on heart is kept at minimum.
3. MECHANISM OF LOCAL BLOOD FLOW
CONTROL
• Rapid change in local vasodilation and
vasoconstriction of arterioles, met
arterioles and precapillary sphincters.
• Occurring within second to minutes.
Acute control
• Slow controlled change in flow over a
periods of days, weeks and months.
• Change involve increase or decrease in
size and no. of actual blood vessels.
Long term
control
4. ACUTE CONTROL OF LOCAL BLOOD FLOW
Effect of tissue metabolism on local blood flow
• Metabolism increase up to 8-times then blood flow
increases acutely about fourfold.
• When oxygen consumption in muscle suddenly
increase, an immediate way to increase supply is
an enhanced extraction of oxygen from Hb in the
flowing blood (I. Sarelius and U. Pohl 2011)
5. ACUTE LOCAL BLOOD FLOW REGULATION WHEN OXYGEN AVAILABILITY
CHANGE
• Oxygen is most important metabolic nutrient and in some circumstances oxygen availability to
the tissue decreases.
This graph depict that when oxygen saturation decreases
to about 25% of normal, the blood
flow is increased to maintain constant oxygen supply of
oxygen to the tissue.
• There are two basis theories for regulation of local blood
Flow (Guyton and Hall textbook of medical physiology. philadelphia: 2011).
They are:
VASODILATOR
THEORY
OXYGEN LACK
THEORY
6. VASODILATOR THEORY
• According to this theory, the greater the rate of metabolism or less the availability of oxygen to a
tissue the greater the formation of vasodilator substance in the tissue.
7. • Many vasodilator theory assume that vasodilator substance is released from the tissue mainly in response to oxygen
deficiency;
• Adenosine is most imp. Local blood flow regulator. Eg:
Reduced Coronary blood flow adenosine release V.D coronary blood flow back to normal.
Heart muscle become more active metabolism O2 degradation of ATP adenosine release
coronary vasodilation occur coronary blood flow.
• Some other mechanism is important in controlling blood flow in skeletal muscles. They are;
Muscle activity enhanced glycolysis and lipolysis (Kiens 2006, Aucouturier et al. 2008) enhanced CO2 production.
In heavy ex. Concentration of lactate (Brechue & Stainsby 1994). Lactate act as VD substance thus blood
flow.
Muscle A.P. lead to release potassium ion as a result conc. Of this ion in early ex. And remain elevated
throughout ex. (Juel et al.2000, Lott et al.2001, Rosendal et al. 2004) and then dilator effect of potassium ion occur
due to hyperpolarization.
8.
9. OXYGEN LACK THEORY
• Oxygen is required ad one of the metabolic nutrient to cause vascular contraction. Therefore in
the absence of oxygen, blood vessels relaxes and naturally dilate.
• Pre capillary sphincter open and close according to tissue need.
• This cyclical opening is called vasomotion.
10. POSSIBLE ROLE OF OTHER NUTRIENT
• Lack of glucose in perfusing blood local tissue vasodilation.
• Vasodilation occur in vitamin deficiency disease eg: beriberi, in which there is deficiency of
vitamin B substances.
11. IN REVIEW OF
CLIFFORD PS. LOCAL CONTROL OF BLOOD FLOW. Adv
Physiol Education, 2011.
• Blood flow is determined by perfusion pressure and vasomotor tone
• The site of local regulation of blood flow is at level of arterioles and feed arteries
• Blood flow through a vessel is governed by physical forces in accordance with poiseuille’s law, as
follows: blood flow,
where P is the pressure gradient across the vessel, r is the vessel radius, n is the viscosity, and l is the
vessel length.
• Because of the fourth power of the radius, small changes in vascular diameter can have substantial
effects on blood flow.
• This article addresses autoregulation, flow mediated and conducted responses and the role of RBC in
the local control of blood flow.
12. AUTOREGULATION
• In any tissue of the body an acute increase in arterial pressure cause immediate rise in blood flow. But within
less than a minute blood flow in most of the tissue return to almost normal level even though arterial pressure
is kept elevated. This return of blood flow toward normal is termed as AUTOREGULATION.
• There are two theories of autoregulation
1. Metabolic theory
2. Myogenic theory
13. METABOLIC THEORY
Arterial pressure
become too great
Too much oxygen and
other nutrient transport
to the tissue
These nutrient constrict
blood vessel and flow
return to normal despite
increased pressure
14. MYOGENIC THEORY
• This theory based on the observation that sudden stretch of small blood vessel cause the smooth muscle vessel wall
to contract for a few second.
• Myogenic response is inherent to vascular smooth muscle.
• Myogenic contraction is initiated by stretch induced vascular depolarization, which then rapidly increase calcium
ion entry from ECF into cell causing them to contract (Hill MA, Davis MJ, 2007).
• Pore forming protein that is tethered to the extracellular matrix on the outside of the cell and the cytoskeleton on the
inside of the cell. When mechanical force applied to extracellular matrix, the pore is modified allowing the influx of
sodium and calcium ions (Drummond HA et al, 2008).
• Myogenic mechanism is important in preventing excessive stretch of blood flow when blood pressure is increased.
High Arterial
pressure
Stretches vessels
Cause reactive vascular
constriction that reduces
blood flow back to
normal
15. SPECIAL EXAMPLE OF METABOLIC CONTROL
OF LBF
• ACTIVE HYPEREMIA
• REACTIVE
HYPEREMIA
16. FLOW MEDIATED RESPONSES
• When blood flow through microvascular
portion of circulation increases, this entrain a
mechanism of dilating upstream.
• The most important vasodilator substance is
endothelium derived relaxing factor (nitric
oxide).
• Many studies shown that increase in shear
stress caused by increase in blood flow is
sensed by endothelial cell, which produce
vasodilation by release of soluble mediators to
adjacent smooth muscle cells.
Philip S. Clifford. Localcontrol of blood flow.
Advances in physiology education. 2011
17. CONDUCTED RESPONSES
• Aka propagated responses
• This principle demonstrated by microinjection or microiontophoresis of a chemical of a chemical
in small quantities at a discrete point on the vessel wall and observing vessel diameter at another
site in the upstream direction (Segal SS, Duling BR.,1987.)
• Application of Ach initiate hyperpolarizationLD
Representative tracings of Em and diameter in response to
acetylcholine microiontophoresis (arrows) in arterioles. SMC
and EC recordings were obtained at the site of stimulation
(local) and 530 micrometer from the stimulus (conducted).
(From Welsh and Segal, 1998, used with permission of the
American Physiological Society.)
18. RED BLOOD CELLS
• Red blood cells release a vasodilator substance during deoxygenation, could regulate their own distribution.
• Bergfeld and Forrester, 1992; first showed that ATP was released from human erythrocytes in response to a
brief exposure to hypoxia. The fact that the increase in ATP was more closely correlated with the percentage
of reduced hemoglobin than the PO2 suggested that ATP release may be related to HB molecule.
19. From Ellsworth et al. Erythrocytes: oxygen sensors and
modulators of vascular tone, American Physiological Society,
2009.
20. LONG TERM REGULATION
• Long term blood flow regulation by changing the degree
of vascularity (angiogenesis).
• Oxygen is important stimulus of regulating tissue
vascularity.
• Role of vascular endothelial growth factors (angiogenic
factor).
• Vascularity of a tissue is determined by the maximum
blood flow need, not by average need.
• Another phenomenon of long term blood flow regulation
is development of collaterals.
21. Adams RH, Alitalo K. Molecular regulation of angiogenesis and lymphangiogenesis. Nat rev mol
cell biol8: 464–478, 2007.
22. COLLATERAL VESSELS AFTER LEFT CIRCUMFLEX
ARTERY OCCLUSION
Cristine L. Heaps, Janet L. Parker. Effects of exercise
training on coronary collateralization and control of
collateral resistance. Journal of applied physiology. 2011.
23. SPECIAL MECHANISM
• Certain tissue have other mechanism of blood flow control:
The kidney have feedback system between the tubules and arterioles
The brain blood flow is controlled by carbon dioxide and hydrogen ion concentration