1. Local Control of Blood Flow
 Each tissue controls its own blood flow in
proportion to its needs.
 Tissue needs include:
1) delivery of oxygen to tissues
2) delivery of nutrients such as glucose, amino
acids, etc.
3) removal of carbon dioxide hydrogen and other
metabolites from the tissues
4) transport various hormones and other
substances to different tissues
 Flow is closely related to metabolic rate of tissues.

2. Variations in Tissue Blood Flow
Brain 14 700 50
Heart 4 200 70
Bronchi 2 100 25
Kidneys 22 1100 360
Liver 27 1350 95
Portal (21) (1050)
Arterial (6) (300)
Muscle (inactive state) 15 750 4
Bone 5 250 3
Skin (cool weather) 6 300 3
Thyroid gland 1 50 160
Adrenal glands 0 .525 300
Other tissues 3.5 175 1.3
Total 100.0 5000 ---
Percent ml/min
ml/min/
100 gm

3. Control of Blood Flow by Tissues
 Local control
 In most tissues, blood flow is proportional to
metabolic needs of tissues
 Nervous System
 Most important for regulating blood flow and
maintaining blood pressure
 Hormonal Control
 Sympathetic action potentials stimulate
epinephrine and norepinephrine

4. Tissue Metabolic Activity Is the Main Factor in
Acute Control of Local Blood Flow
 One of the most fundamental principles of
circulatory function is the ability of each tissue to
control its own local blood flow in proportion to
its metabolic needs
 Metabolic Mechanism
 Any intervention that results in an inadequate oxygen
(nutrient) supply for the metabolic requirements of
the tissues results in the formation of vasodilator
substances which increase blood flow to the tissues.

5. Acute Control of Local Blood Flow
 Increases in tissue metabolism lead to
increases in blood flow.
 Decreases in oxygen availability to tissues
increases tissue blood flow.
 Two major theories for local blood flow are:
1) The vasodilator theory
2) Oxygen demand theory

6. Effect ofTissue Metabolic Rate
onTissue Blood Flow

7. Effect of Tissue Oxygen Concentration
on Blood Flow

8. Acute Local Feedback Control
of Blood Flow
Lack of oxygen?
Formation of vasodilators?
Combination of both??
Metarteriole
Precapillary
Sphincter
Capillary
Relaxation of smooth muscle
Increased Blood Flow

10. Metabolic Mechanisms
 Hypoxia
 Tissue metabolites and ions
 Adenosine
 Potassium ions
 Carbon dioxide
 Hydrogen ion
 Lactic acid

11. Metabolic Control of Local Blood Flow

12. Autoregulation of blood flow when
arterial pressure changes from normal
 Intrinsic ability of an organ to maintain a
constant blood flow despite changes in
pressure
 Possible explanations for Autoregulation:
 Myogenic Mechanism
 Metabolic Mechanism

13. Theories to Explain Autoregulation:
Metabolic Mechanism
When the pressure increases to a tissue, the flow
increases, and excess oxygen and nutrients are
provided to the tissues. These excess nutrients
cause the blood vessels to constrict and the flow
to return nearly to normal despite the increased
pressure.

14. Theories to Explain Autoregulation:
Myogenic Mechanism
 When the lumen of a blood vessel is suddenly expanded,
the smooth muscles respond by contracting in order to
restore the vessel diameter and resistance. The converse
is also true.
 Vascular smooth muscle cells depolarize when stretched.
 Proposed mechanism is stretch of vascular smooth
muscle causes activation of membrane calcium channels.

15. Theories to Explain Autoregulation:
Myogenic Mechanism
P1
F1
↑P
↑F
↑P
F1

16. Long-term Regulation of Blood
Flow
 Long-term regulatory mechanisms which
control blood flow are more effective than
acute mechanism
 Long-term local blood flow regulation occurs
by changing the degree of vascularity of
tissues (size and number of vessels)
 Oxygen is an important stimulus for
regulating tissue vascularity

17. Short and long term
Regulation of Blood Flow

18. Angiogenesis
 Angiogenesis is the growth of new blood vessels
 Angiogenesis occurs in response to angiogenic
factors released from:
1) ischemic tissue
2) rapidly growing tissue
3) tissue with high metabolic rates
 Most angiogenic factors are small peptides such
as vascular endothelial cell growth factors
(VEGF), fibroblast growth factor (FGF), and
angiogenin

19. vascular endothelial growth factor (VEGF)

20. The endothelium plays an active role in
regulating blood flow
 Endothelium is a source of substances that elicit
contraction or relaxation of the vascular smooth
muscle
 Vasoactive substances released from
endothelium:
 Nitric Oxide (NO)
 Endothelium-derived relaxing factor
 Prostacyclin
 Endothelin

21. Control of blood flow from endothelial
cells
 Originally called Endothelium-derived
relaxing factor (EDRF), which is now
identified as nitric oxide
 Rapid flow of blood through the arteries and
arterioles causes significant increase in the
release of nitric oxide
 The nitric oxide relaxes the blood vessels

22. L-Arginine is converted to NO by the enzyme
nitric oxide synthase (NOS)

23. Prostacyclin
 Prostacyclin (PGI2)
 Strong vasodilator
 Inhibits platelet adhesion to the vascular
endothelium

24. Endothelin
 Potent vasoconstrictor
 Increased aldosterone secretion
 Decreased renal blood flow and GFR

25. When Damage to Endothelium Occurs
 Damage to endothelial cells will lead to:
 Decreased Nitric Oxide and Prostacyclin
production
 Increased Endothelin production
 This will lead to:
 Vasoconstriction
 Vasospasm
 Thrombosis