This document discusses the local and humoral regulation of tissue blood flow. It begins by outlining the specific needs of tissues for blood flow, including delivery of oxygen and nutrients and removal of waste. It then describes the mechanisms by which changes in tissue metabolism or oxygen availability alter blood flow, including the vasodilator and oxygen demand theories. The document also discusses acute responses like active and reactive hyperemia, as well as long-term regulation through changes in vascularity and remodeling of blood vessels. Finally, it outlines various humoral factors that can cause vasoconstriction or vasodilation, such as sympathetic nerves, angiotensin, bradykinin, and ions like calcium, potassium, and hydrogen ions

1. 1
L 78: Control of Tissue blood Flow
Dr Shamshad
Majamaah University

2. 1. Enumerate the mechanism of local control of blood
flow in response to tissue needs.
2. Describe the acute and long term mechanism for
regulation of tissue blood flow.
3. Discuss the humoral regulation of circulation.
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3. Specific needs of the tissues for blood flow
1. Delivery of O2 ,nutrients: glucose, AA, FFA
2. Removal of CO2 ,H+ ions
3. Maintain proper concentrations of ions in the tissues
4. Transport of various hormones & other substances to
the different tissues.
Special requirements by certain organs
1. Skin: Determines heat loss from the body thus helps
control body temperature.
2. Kidneys: Allows filter & excrete the waste products of
the body thus regulate body fluid vol. & electrolytes. 3

4. Variations in Blood Flow in Different Tissues and Organs.
Ex:
1] Through the kidneys(1100 ml/min).
Significance
Required to perform excretion of waste products.
Regulate precise composition of the body fluids.
2] Inactive muscles of the body( total of 750 ml/min)
At rest : The metabolic activity of the muscles is very low
During heavy exercise: Metabolic activity increases >60-fold so
also the blood flow to 20-fold i.e (16,000 ml/min).
Blood flow depends on requirement & function of tissues/organ.
4

5. Importance of Blood Flow Control by the Local Tissues.
Why not continuously provide a very large blood flow?
● This action requires more blood flow than the heart can
pump.
● Thus blood flow to each tissue is regulated at the minimal
level that will supply the tissues precise amount of blood
● By this the tissues never experience oxygen nutritional
deficiency and the workload on the heart is kept at a
minimum.
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6. Mechanisms by which changes in tissue metabolism or oxygen
availability alter tissue blood flow
Exact mechanism Unknown
1] The vasodilator theory (Widely accept theory)
2] The oxygen demand theory.
1:Increase metabolism increases bl flow
2:Hypoxia increases bl flow:
high altitude, pneumonia, CO, cyanide poisoning …
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1 2

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Vasodilator Theory [ Adenosine play special role]
 Increased metabolism / less availability of O2 / less nutrients to
tissue
 Leads to increased rate of formation of vasodilator substances in
the tissue.
 Which then diffuses through the tissues to the precapillary
sphincters, metarterioles & arterioles to cause Vasodilation.
Ex: Adenosine, CO2, Adenosine phosphate compounds, Histamine,
K+ ions, and H+ ions.

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Ex. Increase metabolism increases heart activity and increase in
O2 utilization. Followed by
 decreased oxygen concentration in the heart muscles
 Result in degradation of ATP
Increase in release of adenosine.
Adenosine leaks out of the heart muscle cells
cause coronary vasodilation to meet the demands of the active
heart.

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Oxygen / Nutrient Demand Theory
 O2 causes vascular muscle contraction (with other nutrients).
 In absence of adequate O2, the blood vessels relaxes & dilate.
Ex:
 Increase metabolism in the tissue increases utilization of O2
Leads to decrease availability of O2 to the smooth muscles of
local blood vessels.
Finally causing local vasodilation

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Vasomotion

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 At the origin of the capillary is a precapillary sphincter,
 Around the metarterioles are several other smooth muscle
fibers.
 The precapillary sphincters and metarterioles open and close
cyclically several times per minute, with the duration of the
open phases proportional to the metabolic needs of the tissues
for oxygen.
 The cyclical opening and closing is called vasomotion.

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 Lack of glucose in the perfusing blood can cause local tissue
vasodilation.
 Deficiency of Vitamin :Thiamine, Niacin, and Riboflavin.
Ex:(Beriberi)
 2-3 fold increase in peripheral vascular blood flow
Mechanism: O2 induced phosphorylation/ATP synthesis in the cells
required these vitamins
Deficiency of these Vit. leads to diminished smooth muscle
contractile ability thus
 Causing local vasodilation .
Role of Other Nutrients

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A:Active hyperemia :
During highly Active metabolism
 Ex: Exercising muscle,
 hyper secretory phase of GIT gland
or increased mental activity of brain .
 The rate of blood flow through the tissue increases 20 folds
 Due to dilation of local blood vessels .
 Significance: The active tissue receives the additional nutrients
that are required to sustain its new level of function.
Special Examples of Acute “Metabolic” Control of
Local Blood Flow

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B:Reactive hyperemia
 When the blood supply to a tissue is blocked for a few
seconds to hours And then unblocked.
 Blood flow thru’ the tissue increases immediately
to 4-7 times normal.
 Significance : Repay tissue oxygen deficit that occurred
during the period of occlusion.

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1:Endothelial Derived Relaxing Factors(EDRF)
Ex: Nitric Oxide(NO)
Released from healthy endothelial cells
in response to physical &chemical stimuli.
Action : larger vessels
2:Endothelial Derived Constricting Factors(EDCF) :
cause vasoconstriction
Released during crushed injury
Action: Prevent bleeding.
Endothelial derived factors

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Rapid increase of arterial pr causes sudden increase in blood flow.
Within few second blood flow returns backs to almost normal even
through there is elevated pr.
This return of flow toward normal is called Autoregulation.
b/w BP of 70 - 175 (mm Hg) the blood flow increases only 20 – 30%
Autoregulation is even more precise in brain & heart.
Explained by :
1) Metabolic theory
2) Myogenic theory.
Autoregulation of Blood Flow
During Changes in Arterial Pressure

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The Myogenic theory
High arterial pr stretches the vessel
causes reactive vascular constriction
that reduces blood flow nearly back to normal.
At low pressures, the degree of stretch of the vessel is less
the smooth muscle relaxes  reducing vascular resistance
help to return flow toward normal.
The myogenic response is inherent to vascular smooth muscle and
can occur in the absence of neural or hormonal influences.
Site: arterioles also in arteries, venules, veins, and lymphatic
vessels.
Significance : Help prevent excessive stretching of blood vessels
when blood pressure is increased.
The role of the myogenic mechanism in blood flow regulation is
unclear

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• Change in degree of vascularity (Angiogenesis).
• Oxygen stimulates tissue vascularity
• Vascular endothelial growth factors (Angiogenic factors).
• Vascularity is determined by maximum need of blood flow to
tissue.
• Development of collaterals.
Long term regulation

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• Angiogenesis is physical reconstruction of tissue vasculature
• Duration: days.
• In neonates rapid growth .
• Stimulant: Oxygen deficit.
• When blood vessels Not in use disappear:
• Angiostatin
• Endostatin.

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• Chronic Changes in Blood Flow or BP Vascular growth leads to
remodeling
• Ex: after several months of chronic exercise training, vascularity of
the trained muscles increases to accommodate their higher blood
flow requirements.
By
• 1:Changes in capillary density,
• 2:Changes in the structure of large blood vessels in response to long-
term changes in blood pressure and blood flow.
• When BP is chronically elevated above normal, Ex: the large & small
arteries and arterioles remodel to accommodate the increased
mechanical wall stress of the higher BP.

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• Small arteries & arterioles vasoconstrict , which helps autoregulate
tissue blood flow,
• vasoconstriction decreases lumen diameter, tends to normalize the
vascular wall tension (T),
• the smaller lumen diameter, a process called inward eutrophic
remodeling, with no change in the total cross sectional area of the
vascular wall.
• In larger arteries that do not constrict in response to the increased
BP, the vessel wall is exposed to increased wall tension that stimulates
a hypertrophic remodeling response and an increase in the cross-
sectional area of the vascular wall.

24. Humoral control of the circulation is by substances secreted or
absorbed into the body fluids :hormones & locally produced
factors.
VASOCONSTRICTOR AGENTS
Sympathetic NS(Norepinephrine & Epinephrine)
NE powerful vasoconstrictor compared to epinephrine
Epinephrine act as vasodilator of coronary arteries during
increased heart activity.
stress or exercise, releases norepinephrine, which excites the
heart and contracts the veins and arterioles.
Also secreted from adrenal medulla
Action:
Direct nerve stimulation and
Indirect effects of NE /E in the circulating blood.

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Angiotensin II. Powerful vasoconstrictor substance (small
arterioles).
• This hormone plays an integral role in the regulation of
arterial pressure
Vasopressin.(ADH)
• More powerful than angiotensin II
• Formed in hypothalamus transported by axons to the
post pituitary , secreted into the blood.
Plays little role in vascular control.
Major role in water reabsorption from the renal tubules
back into the blood controls body fluid volume.

26. Vasodilators
Inactive kallikrein
Maceration of the blood
Tissue inflammation
chemical or physical effects
Active kallikrein
alpha2-globulin kallidin
bradykinininactivated by carboxypeptidase /
converting enzyme
kallikrein inhibitor
Regulates flow to skin, salivary glands, gastrointestinal glands.
Persists few minutes
Arteriole dilators and increase capillary permeability

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Histamine.
Released: Due damage/inflammation/allergic reaction of
tissues
Derived :Mast cells and basophils
powerful vasodilator effect on the arterioles and increase
greatly capillary porosity, allowing leakage of both fluid and
plasma protein into the tissues.
Pathologically can lead to edema.

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Ions Effect Action
smooth muscle
Ca2
+ ions Vasoconstriction Stimulate
K+ ions Vasodilation Inhibit
Mg2
+ ions Powerful vasodilation Inhibit.
H+ ions Dilation of arterioles decrease in pH
CO2 Moderate vasodilation in most tissues
Marked vasodilation in brain.
Anions
Acetate & Citrate
mild vasodilation
Control of blood flow by Ions