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Local Control of Blood Flow
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Reading
Klabunde, Cardiovascular Physiology
Concepts Chapter 7 (Organ Blood Flow) pages 141-151.
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Regulation of Peripheral Blood Flow
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Acute Local Feedback Control
of Blood Flow
Lack of oxygen?
Formation of vasodilators?
Combination of both??
Metarteriole
PrecapillarySphincter
Capillary
Relaxation of smooth muscle
Increased Blood Flow
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Metabolic Mechanisms
Hypoxia
Tissue metabolites and ions
Adenosine
Potassium ions
Carbon dioxide
Hydrogen ion Lactic acid
Inorganic phosphate
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Examples of Metabolic Control
of Local Bloodflow
Active Hyperemia
Reactive Hyperemia
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Active Hyperemia
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Reactive Hyperemia
Within limits the peak blood flow and the
duration of the of the reactive hyperemia
are proportional to the duration of the
occlusion
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Intrinsic Control of
Local Blood Flow:
Autoregulation
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Autoregulation
Intrinsic ability of an organ to maintain a
constant blood flow despite changes in
perfusion pressure
Possible explanations for Autoregulation:
Myogenic Mechanism
Metabolic Mechanism
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Ohms Law
RPPQ va
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Cerebral Autoregulation
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Autoregulation
Autoregulation
Time
No Autoregulation
No Autoregulation
Resistance
Flow
Pressure
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Theories to Explain Autoregulation:
Myogenic Mechanism
P1
Q1
P
Q
P
Q1
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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 excessnutrients cause the blood vessels to constrict
and the flow to return nearly to normal despite
the increased pressure.
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Intrinsic Control of
Local Blood Flow:
Endothelial Factors
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The endothelium plays an active role in
regulating the microcirculation
Endothelium is a source of substances that elicitcontraction or relaxation of the vascular smoothmuscle
Vasoactive substances released fromendothelium: Nitric Oxide (NO)
Endothelium-derived relaxing factor
Prostacyclin
Endothelin
Endothelial-derived hyperpolarizing factor (EDHF)
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Nitric Oxide
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Nitric Oxide
Generated from amino acid L-arginine
Generated from NO synthase
Increases GMP concentration which produces relaxationby decreasing cytosolic free calcium
Very short half-life (6 seconds) Due to rapid oxidation to nitrite and nitrate
Also due to binding by substances such as hemoglobin
NO is a gas and must be delivered by an inhaleddelivery system
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Nitric Oxide
NO production is stimulated by:
Shearing forces acting on the endothelium
Acetylcholine
Bradykinin
Histamine
Insulin
Substance P
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Nitric Oxide
Important functions in cardiovascular system:
Vasodilation
Inhibition of vasoconstrictor influences
Inhibition of platelet adhesion to the vascularendothelium
Inhibition of leukocyte adhesion to the vascular
endothelium
Antiproliferative
Free radical scavenger
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Nitric Oxide
ShuntReduced
NO
NO
NO
NO
NO
NO
NO
NO -
Hgb
NO
NO
NO
Nitric oxide-induced pulmonary vasodilation
allows blood to preferentially flow by
ventilated lung units
Rapid binding of NO by
Hgb limits hemodynamic
effects of NO
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Prostacyclin
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Prostacyclin
Prostacyclin synthase in endothelial cells
acts on cyclo-endoperoxide products to
form Prostacyclin (PGI2)
Prostacyclin (PGI2)
Strong vasodilator
Inhibits platelet adhesion to the vascular
endothelium
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Endothelin
Synthesized by endothelium
Potent vasoconstrictor
Other actions: Increased aldosterone secretion
Increased cardiac inotropy and chronotropy
Decreased renal blood flow and GFR
Releases atrial natriuretic peptide
In failing heart, contributes to calciumoverload and hypertrophy
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Endothelin
Implicated in the pathogenesis of:
Hypertension
Vasospasm
Heart failure
Pulmonary hypertension
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When Damage to Endothelium Occurs
Damage to endothelial cells will lead to:
Decreased Nitric Oxide and Prostacyclinproduction
Increased Endothelin production
This will lead to: Vasoconstriction
Vasospasm
Thrombosis
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THE END