18. local control of blood flow-1

8/7/2019 18. Local Control of Blood Flow-1

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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

18. local control of blood flow-1

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