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
Hagen - Poiseuille 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
Viscosity of the blood is not constant, it is proportional to the haematocrit and to the
velocity of blood flow. The blood flow is not laminar in fact, erythrocytes concentrate
in the middle (plasma skimming). The turbulent flow.
Elasticity of vessels.
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 (Faraday, 1791-1867)
❖ the electromagnetic flowmeter
❖ an electromotive force is generated in the
blood (as a conductor) when it moves through
a magnetic field
❖ can detect changes in the velocity <0.01 s → recording of both
steady blood flow and its pulsatile changes
❖ this electromotive force (measured with an electrode placed on
the vessel surface) is proportional to the velocity of blood flow
❖ change of the wave length
(frequency) is proportinal to
the velocity of blood flow
Methods for Measuring Blood Flow
2. Doppler Effect (Christian Doppler, Praque 1842)
❖ the ultrasonic Doppler flowmeter; most common
• ultrasonic waves of a known wave length (frequency) are sent
into a vessel diagonally along the blood stream from a subtle
piezoelectric crystal
• 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
Methods for Measuring Blood Flow
3. Plethysmography
❖ usually as the venous occlusion plethysmography
• venous drainage of the limb
is stopped (e.g. with an arm
cuff)
• increasing volume of the limb
(expelling water from closed chamber,
measured as a change of its volume)
is lineary proportional to the
arterial inflow of blood
❖ can be used on limbs
Methods for Measuring Blood Flow
3. Plethysmography
❖ usually as the venous occlusion plethysmography
• venous drainage of the limb
is stopped (e.g. with an arm
cuff)
• increasing volume of the limb
(expelling water from closed chamber,
measured as a change of its volume)
is lineary proportional to the
arterial inflow of blood
❖ 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
(a sample of the mixed venous blood bleeded from the pulmonary artery with a
catheter inserted to the brachial vene)
• blood flowing from the lungs to the left heart – about 200 ml O2 / 1 l
(a sample of the arterial blood from any artery, arterial O2 content is uniform)
• The total O2 consumption is 250
ml / 1 min.
(O2 decay in the expired air compared to
the inspired air, oximeter)
250 ml O2 / min
= 5 l / min
50 ml O2 / l
CO =
Q =
AV diff
A / time
- Direct Fick Method
Methods for Measuring Blood Flow
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]
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
❖ thermodilution
a cold saline (indicator) is injected into the right atrium through a double lumen
catheter; the change of blood temperature (inversely proportinal to the blood flow) is
recorded in the pulmonary artery using a thermistor in the other side of the catheter
• estimation of the averaged
concentration of the indicator in the
arterial blood after a single
circulation (C, [mg/ml])
Regulation
Systemic
Local
Regulation of Blood Flow
Q = P . πr4 / 8ηl
Resting Tone (intermediary vascular muscle tone at rest)
❖ due to 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 Local Substances
A. Acute
B. Chronic
seconds to minutes, but incomplete (about ¾ of the
desired effect)
hours, days to weeks , even months
A. Acute
1. Metabolic Autoregulation
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 (CO2, lactic acid,
adenosine, K+, phoshate), ↓ pH, ↑ osmolarity in
the interstitium, ↑ tissue temperature (the
metabolic heat); ↓ pO2 (the second theory based
on the lack of O2 and 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
(increase of the blood flow induced
by an increased metabolic activity of
the tissue)
reactive hyperemia
(transient increase of the blood flow
exceeding its common level after
release of an occlusion; it gradually
returns to the control level)
(15-, 30- and 60-s occlusions of the
femoral artery in a dog)
Regulation of Blood Flow - Local
1. Metabolic Autoregulation
2. Myogenic Autoregulation
3. Regulation Mediated by Local Substances
A. Acute
B. Chronic
seconds to minutes, but incomplete (about ¾ of the
desired effect)
hours, days to weeks , even months
A. Acute
2. Myogenic Autoregulation
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
Myogenic Autoregulation
Regulation of Blood Flow - Local
1. Metabolic Autoregulation
2. Myogenic Autoregulation
3. Regulation Mediated by Local Substances
A. Acute
B. Chronic
seconds to minutes, but incomplete (about ¾ of the
desired effect)
hours, days to weeks , even months
A. Acute
3. Regulation Mediated by Local Substances
Regulation of Blood Flow - Local
Regulation Mediated by Local Substances
❖ important in the intermediate and larger arteries back
upstream where the metabolic tissue changes causing
dilatation of the microvessels cannot directly reach
endothelial-derived relaxing factor (EDRF) – NO
(half-life in the blood only 6 s) → vasodilatation
❖ synthesized in the endothelial cells of arteriols and small
arteries due to the shear stress induced by the flowing
blood (deforms the endothelial cells in the direction of flow)
❖ its synthesis stimulated by the products of thrombocyte
aggregation (to keep vessels with intact endothelium permeable)
and also by many primary vasoconstrictive substances
Regulation of Blood Flow - Local
Regulation Mediated by Local Substances
endothelial-derived relaxing factor (EDRF) – NO
Regulation of Blood Flow - Local
Regulation Mediated by Local Substances
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. (aspirin)
Regulation of Blood Flow - Local
Regulation Mediated by Local Substances
endothelins
❖ several similar polypeptides synthesized by the 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, unknown function (maybe vasodilatation –
through increased synthesis of NO - and developmental effects)
❖ the exact physiological role not known
❖ released from the endothelial cells in the damaged tissue →
vasoconstriction → 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, specific mechanisms
❖ local vasoconstriction of damaged arteries and
arteriols
❖ vasoconstriction (vasodilatation) induced by a
decrease (increase) of the tissue temperature
❖ specialized tissues (kidneys, brain, etc.)
(due to release of serotonin and thromboxane A2 from
thrombocytes and endothelin-1 from the endothelial cells)
Regulation of Blood Flow - Local
1. Metabolic Autoregulation
2. Myogenic Autoregulation
3. Regulation Mediated by Local Substances
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
It is especially important in case of the long-term change of
metabolic demands of a tissue - to provide sufficient blood flow
without circulation overload.
Regulation of Blood Flow - Local
Chronic regulation
❖ mediated by changes of the tissue vascularity
❖ proceeds fast (within days) in the young individuals and in
newly formed tissue (new scar, tumor tissue) vs. within
even months in the elderly and differentiated tissues
❖ the key role – lack of O2 (higher altitude, retrolental
fibroplasia in premature newborns after the curative stay in
the oxygen tent) and also nutrients
❖ identified number of factors increasing grow of new vessels
- 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.)
(↑ BP → reflex bradycardia, ↓ CO)
❖ angiotensin II
↓ BP → ↑ sekretion of renin → formation of angiotensin II
→ generalized vasoconstriction (+ ↑ water intake and ↑ aldosterone)
❖ vasopressin (antidiuretic hormone)
→ generalized vasoconstriction (+ ↑ reabsorption of water in the kidneys)
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 – relaxation of the measangial cells and, thus, ↑
glomerular filtration rate, + inhibition of vasopressine secretion, + ↓ aldosterone)
through EDRF (vasoconstrictor by itself)
• 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
regulation of the blood flow and
leak of fluids from capillaries in
the inflamed tissue
+
regulation of the blood flow in
the skin, salivary and GIT
glands in common conditions
(similar to histamine)
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