Regulation of Blood Flow
Assoc. Prof. MUDr. Markéta Bébarová, Ph.D.
Dept. of Physiology, Faculty of Medicine, Masaryk University
This presentation includes only the most
important terms and facts. Its content by
itself is not a sufficient source of
information required to pass the
Physiology exam.
Definition of Blood Flow
mathematical formulation – analogy with the electric current
Ohm´s law
I = U / R Q = P / R
Q blood flow
P difference of pressure at the
R resistance of the vessel
(peripheral resistance)
beginning and at the end of
a vessel
Definition of Blood Flow
Poiseuille – Hagen formula
r radius of the vessel
η viscosity of the blood
l length of the vessel
This formula applies to the steady laminar flow in a rigid tube!
Q = P / R
R = 8ηl / πr4
Q = P . πr4 / 8ηl
Blood viscosity is not constant, plasma skimming, turbulent flow, elastic vessels!
Definition of Blood Flow
Poiseuille – Hagen formula
r radius of the vessel
η viscosity of the blood
l length of the vessel
Q = P / R
R = 8ηl / πr4
Q = P . πr4 / 8ηl
P
Q rigid tube
critical closing pressure
vessel
Methods for Measuring Blood Flow
A. with a cannula inserted into a vessel
1. Electrical Induction Principle
B. without direct contact with the blood flow
3. Plethysmography
2. Doppler Effect
4. Fick Principle
Methods for Measuring Blood Flow
1. Electrical Induction Principle
❖ the electromagnetic flowmeter
❖ can detect changes in the velocity <0.01 s → recording of both
steady blood flow and its pulsatile changes
❖ the generated electromotive force is proportional to the
velocity of blood flow
Guyton and Hall.
Textbook of Medical Physiology, 11th edition
❖ change of the wave length
(frequency) is proportinal to
the velocity of blood flow
Methods for Measuring Blood Flow
2. Doppler Effect
❖ the ultrasonic Doppler flowmeter; most common
• ultrasonic waves of a known wave length (frequency)
• waves reflect from the red and white blood cells → a change (↑)
of the wave length (↓ frequency)
• reflected waves are picked up by a sensor
❖ both steady blood flow and its pulsatile changes can be measured
f = f0 (1 + )
v0
v
Methods for Measuring Blood Flow
3. Plethysmography
❖ usually as the venous occlusion plethysmography
❖ can be used on limbs
Guyton and Hall. Textbook of Medical Physiology, 11th edition
• venous drainage of
the limb is stopped
(e.g. with an arm cuff)
• increasing volume of
the limb is lineary
proportional to the
arterial inflow of blood
• venous drainage of
the limb is stopped
(e.g. with an arm cuff)
• increasing volume of
the limb is lineary
proportional to the
arterial inflow of blood
Methods for Measuring Blood Flow
3. Plethysmography
❖ usually as the venous occlusion plethysmography
❖ can be used on limbs
http://schueler.ws/?page_id=21
4. Fick Principle
Methods for Measuring Blood Flow
The blood catches 50 ml O2 / 1 l
during passage through the lungs.
• blood flowing from the right heart to the lungs – about 150 ml O2 / 1 l
• blood flowing from the lungs to the left heart – about 200 ml O2 / 1 l
• The total O2 consumption is 250
ml / 1 min.
250 ml O2 / min
= 5 l / min
50 ml O2 / l
CO =
Q =
AV diff
A / time
- Direct Fick Method
Guyton and Hall. Textbook of Medical Physiology, 11th edition
Methods for Measuring Blood Flow
4. Fick Principle – Method of Indicatory Gas
❖ to determine the instantaneous blood flow through a
specific tissue
❖ for example the cerebral or coronary blood flow using
inhaled nitrous oxide N2O – Kety method
N2O removed from blood by brain / time
averaged arteriovenous difference of N2O
cerebral blood flow =
N2O concentration in the venous blood
Methods for Measuring Blood Flow
4. Fick Principle - Indicator Dilution Technique
• known amount of an indicator (dye or radioactive isotope) is
injected into a peripheral (an arm) vein (A, [mg])
• concentration of the indicator in
serial samples of the arterial blood
is determined
• estimation of the averaged
concentration of the indicator in the
arterial blood after a single
circulation (C, [mg/ml])
A
C (t2 - t1)
CO =
[mg]
[mg.ml-1.s]
Ganong´s Review of Medical Physiology, 23rd edition.
❖ thermodilution
Regulation
Systemic
Local
Regulation of Blood Flow
Q = P . πr4 / 8ηl
Resting Tone
❖ tonic activity of vasocontrictive sympathetic fibres
❖ a role might play also: myogenic response of vessels to the blood
pressure (later), high concentration of O2 in the arterial blood, Ca2+
Basal Tone
❖ in response to denervation; due to spontaneous depolarizations of the
vascular smooth muscles
Regulation of Blood Flow - Local
1. Metabolic Autoregulation
2. Myogenic Autoregulation
3. Regulation Mediated by Endothelium
A. Acute
B. Chronic
seconds to minutes, but incomplete (about ¾ of the
desired effect)
hours, days to weeks , even months
A. Acute
Regulation of Blood Flow - Local
Metabolic Autoregulation
Preferred to the systemic regulation in case of hypoxia (to
preserve the adequate tissue perfusion).
insufficient blood flow
↑ concentration of metabolites, ↓ pH, ↑ osmolarity
in the interstitium, ↑ tissue temperature; ↓ pO2,
nutrients
vasodilatation
It plays the key role in e.g. brain, heart and skeletal muscles.
↑ metabolic demands of a tissue
↓ or stopped blood supply
Regulation of Blood Flow - Local
Metabolic Autoregulation
active hyperemia
reactive hyperemia
It plays an important role in the brain and kidneys.
Regulation of Blood Flow - Local
Myogenic Autoregulation (Bayliss effect)
blood pressure↑
↑ blood flow and tension in the vascular wall↑
mechanical stimulation, depolarization and
subsequent contraction of the smooth muscle cells in
the vascular wall → vasoconstriction
return of the blood flow back on the original level
T = P . r
Law of LaplaceQ = P / R
Regulation of Blood Flow - Local
Regulation Mediated by Endothelium
endothelial-derived relaxing factor (EDRF) – NO
→ vasodilatation
❖ synthesized in the endothelial cells of arteriols and small
arteries due to the shear stress induced by the flowing
blood
❖ synthesis stimulated by the products of thrombocyte
aggregation and also by many primary vasoconstrictive
substances
Regulation of Blood Flow - Local
Regulation Mediated by Endothelium
endothelial-derived relaxing factor (EDRF) – NO
Guyton and Hall. Textbook of Medical Physiology, 11th edition
Regulation of Blood Flow - Local
Regulation Mediated by Endothelium
prostacyclin
❖ synthesized in the endothelial cells from the arachidonic acid
❖ inhibition of thrombocyte aggregation and vasodilation
thromboxane A2
❖ synthesized from the arachidonic acid by thrombocytes
❖ support of thrombocyte aggregation and vasoconstriction
A balance between them is crucial for formation of the
localized clot and preservation of the blood flow.
Regulation of Blood Flow - Local
Regulation Mediated by Endothelium
endothelins
❖ polypeptides synthesized by endothelial cells (ET-1, ET-2,
ET-3 )
❖ ET-1 – one of the most potent vasoconstrictive substances
❖ 2 endothelin receptors:
ETA – specific for ET-1, in many tissue vessels, → vasoconstriction
ETB – ET-1 to ET-3, function?
❖ the exact physiological role not known
❖ restricts bleeding, play a role in closing ductus arteriosus at birth
Serotonin (5-OH tryptamine)
❖vasodilatory effect
• in an undamaged tissue
• through increased activity of NO synthase
❖vasoconstrictive effect
• in a damaged tissue
• direct local effect
• released from thrombocytes
Regulation of Blood Flow - Local
Regulation of Blood Flow - Local
Other mechanisms
❖ damaged vessels
❖ temperature, …
❖ specialized tissues (kidneys, brain, etc.)
Regulation of Blood Flow - Local
1. Metabolic Autoregulation
2. Myogenic Autoregulation
3. Regulation Mediated by Endothelium
A. Acute
B. Chronic
seconds to minutes, but incomplete (about ¾ of the
desired effect)
hours, days to weeks , even months
Regulation of Blood Flow - Local
Chronic regulation
Especially important in case of the long-term change of
metabolic demands of a tissue - to provide sufficient blood flow
without circulation overload.
Guyton and Hall.
Textbook of Medical
Physiology, 11th edition
Regulation of Blood Flow - Local
Chronic regulation
❖ mediated by changes of the tissue vascularity
❖ fast in young individuals and in newly formed tissue
❖ the key role – lack of O2, also nutrients
❖ angiogenic or vascular growth factors - small peptides, best
characterized: vascular endothelial growth factor (VEGF),
fibroblast growth factor, and angiogenin
Regulation of Blood Flow - Local
Chronic regulation
Guyton and Hall - Textbook of Medical Physiology (12th edition)
unstimulated muscle regularly stimulated muscle
Regulation of Blood Flow
Local
Systemic
B. Humoral
A. Neural
B. Humoral
Regulation of Blood Flow - Systemic
Vasoconstrictive substances
Humoral regulation
❖ epinephrine (high levels)
→ vasodilatation in the skeletal muscles,
liver and coronary arteries (β2-rec.)
→ vasoconstriction in other tissues
❖ norepinephrine
→ generalized vasoconstriction (α1-rec.)
❖ angiotensin II
→ generalized vasoconstriction (+ ↑ water intake and ↑ aldosterone)
❖ vasopressin (antidiuretic hormone)
→ generalized vasoconstriction (+ ↑ reabsorption of water in the kidneys)
Ganong´s Review of Medical Physiology, 23rd edition
Regulation of Blood Flow - Systemic
Vasodilatory substances
Humoral regulation
• released in tissues (from the mast cells), or from basophiles in the
blood, during tissue damage or inflammation (also allergic)
❖histamine
→vasodilatation of arteriols + ↑ permeability of capillaries
(edemas; anaphylactic shock)
❖ VIP (vasoactive intestinal peptide)
→ vasodilatation (+ many other effects in GIT, namely relaxation of the
intestinal smooth muscles including sphincters)
❖ atrial natriuretic peptide (ANP)
→ ↓ reactivity of the vascular smooth muscles on vasoconstrictive
stimulation (+ ↑ natriuresis - mechanisms)
through EDRF
• small polypeptides, half-life - several minutes
Regulation of Blood Flow - Systemic
Vasodilatory substances
Humoral regulation
❖kinins - bradykinin and lysylbradykinin (kallidin)
→vasodilatation of arteriols + ↑ permeability of capillaries
inflamed tissue
+
skin, salivary and GIT glands (in
common conditions)
(similar to histamine)
Ganong´s Review of Medical Physiology, 23rd edition
Regulation of Blood Flow - Systemic
Other factors
Humoral regulation
❖ions
vasoconstriction: ↑ Ca2+, slightly ↓ H+
vasodilatation: ↑ K+, ↑ Mg2+; ↑ H+, notably ↓ H+
acetate, citrate (anions) – only mild effect