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 tissues2) delivery of nutrients such as glucose, amino

acids, etc.3) removal of carbon dioxide hydrogen and other

metabolites from the tissues4) transport various hormones and other

substances to different tissues

Flow is closely related to metabolic rate of tissues.

Variations in Tissue Blood Flow

Brain 14 700 50Heart 4 200 70Bronchi 2 100 25Kidneys 22 1100 360Liver 27 1350 95 Portal (21) (1050) Arterial (6) (300)Muscle (inactive state) 15 750 4Bone 5 250 3Skin (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

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

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.

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 theory2) Oxygen demand theory

Effect of Tissue Metabolic Rate on Tissue Blood Flow

Effect of Tissue Oxygen Concentration on Blood Flow

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

Metabolic Mechanisms

Hypoxia

Tissue metabolites and ions Adenosine Potassium ions Carbon dioxide Hydrogen ion Lactic acid

Metabolic Control of Local Blood Flow

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

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.

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.

Theories to Explain Autoregulation:Myogenic Mechanism

P1

F1

↑P

↑F

↑P

F1

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

Short and long term Regulation of Blood Flow

Angiogenesis

Angiogenesis is the growth of new blood vessels

Angiogenesis occurs in response to angiogenic factors released from:1) ischemic tissue2) rapidly growing tissue3) 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

vascular endothelial growth factor (VEGF)

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

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

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

Prostacyclin

Prostacyclin (PGI2)

Strong vasodilator

Inhibits platelet adhesion to the vascular endothelium

Endothelin

Potent vasoconstrictor

Increased aldosterone secretion

Decreased renal blood flow and GFR

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