Regulation of Blood Flow Assoc. Prof. MUDr. Markéta Bébarová, Ph.D. Dept. of Physiology, Faculty of Medicine, Masaryk University mathematical formulation - analogy with the electric current Ohm's law l = U/R Q = AP / R AP blood flow difference of pressure at the beginning and at the end of a vessel resistance of the vessel (peripheral resistance) Poiseuille - Hagen formula Q = AP . TTr4 / 8r|l sse viscosity of the blood length of the vessel This formula applies to the steady laminar flow in a rigid tube! Blood viscosity is not constant, plasma skimming, turbulent flow, elastic vessels! Q = AP / R Poiseuille - Hagen formula R = 8r|l /nr4 r radius of the vessel q viscosity of the blood I length of the vessel Q = AP . "nr4 / 8r|l A. with a cannula inserted into a vessel B. without direct contact with the blood flow 1. Electrical Induction Principle 2. Doppler Effect 3. Plethysmography 4. Fick Principle 1. Electrical Induction Principle ❖ the electromagnetic flowmeter ❖ the generated electromotive force is proportional to the velocity of blood flow ❖ can detect changes in the velocity <0.01 s -» recording of both steady blood flow and its pulsatile changes 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 (t) of the wave length (1 frequency) reflected waves are picked up by a sensor change of the wave length (frequency) is proportinal to the velocity of blood flow f = f0(1 + ❖ both steady blood flow and its pulsatile changes can be measured 3. Plethysmography ❖ usually as the venous occlusion plethysmography ❖ can be used on limbs 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 um Guyton and Hall. Textbook of Medical Physiology, 11th edition 3. Plethysmography ❖ usually as the venous occlusion plethysmography ❖ can be used on limbs • 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 4. Fick Principle - Direct Fick Method Q = A/time blood flowing from the right heart to the lungs - about 150 ml 02 /1 blood flowing from the lungs to the left heart - about 200 ml 02 /1 I The blood catches 50 ml 02 /1 I ^^HB ffl^^^^^H during passage through the lungs.^^^^^HH\ ^Jl^H^^H The total 02 consumption is 250 l^^^^^r^ JK* ^^^H ml /1 min. I^^^^K mlL, 250 ml Oo/min CO =--- = 5 I / min 50 ml 02 /1 Guyton and Hall. Textbook of Medical Physiology, 11th edition Vi 1 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 N20 - Kety method N20 concentration in the venous blood / N20 removed from blood by brain / time cerebral blood flow = - averaged arteriovenous difference of N20 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 HP^^^^^^^^^I serial samples of the arterial blood BffiEr^B^^^^B determined BiJIft^^BS^^H • estimation of the averaged BBIflB^^fcfiSM concentration of the indicator in the taJJflMW^^^BBI arterial blood after a single KSlf^B^^^^^M circulation (C, [mg/ml]) BBII^Km^SeSBI co = A [mg] C (t2-[mg.mM.s] Ganong's Review of Medical Physiology, 23rd edition. ❖ thermodilution 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 02 in the arterial blood, Ca2+ Basal Tone ❖ in response to denervation; due to spontaneous depolarizations of the vascular smooth muscles Regulation Local Systemic B. Vasoconstriction and vasodilatation Pressor areo la Neuronal Sympathetic 1b Neuronal Sympathetic \ tonus y Parasympathetic system (salivary glands, genitalia) M Adenosine, Pco2'+ H\ K+etc. _ NOf A PCEj.PCbf 2b local Brady kinin, a kallidin ADH(V0, epinephrine, angiotensin II 3a Hormonal i ■ /o \ Acetylcholine (M), Epinephrine (p2) y ^ 3b histamine (Ht), Hormonal endothelin-1 (ETB) Despopoulos, Color Atlas of Physiology © 2003 Thieme A. Acute seconds to minutes, but incomplete (about % of the desired effect) 1. Metabolic Autoregulation 2. Myogenic Autoregulation 3. Regulation Mediated by Endothelium B. Chronic hours, days to weeks, even months 00 ca 1 Metabolic Autoregulation „. . . . . . ,. / t metabolic demands of a tissue insufficient blood flow ' . .. I or stopped blood supply t concentration of metabolites, j pH, f osmolarity in the interstitium, | tissue temperature; | p02, nutrients vasodilatation Preferred to the systemic regulation in case of hypoxia (to preserve the adequate tissue perfusion). It plays the key role in e.g. brain, heart and skeletal muscles. Metabolic Autoregulation active hyperemia reactive hyperemia 00 ca 1 Myogenic Autoregulation (Bayliss effect) T blood pressure -> T blood flow and T tension in the vascular wall Q = AP / R II Law of Laplace T = P . r mechanical stimulation, depola subsequent contraction of the smooth muscle cells in the vascular wall -» vasoconstriction return of the blood flow back on the original level It plays an important role in the brain and kidneys. 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 B. Vasoconstriction and vasodilatation Pressor areo la Neuronal Sympathetic 1b Neuronal Sympathetic \ tonus y Parasympathetic system (salivary glands, genitalia) M Adenosine, Pco2'+ H\ K+etc. _ NOf A PCEj.PCbf 2b local Brady kinin, a kallidin ADH(V0, epinephrine, angiotensin II 3a Hormonal i ■ /o \ Acetylcholine (M), Epinephrine (p2) y ^ 3b histamine (Ht), Hormonal endothelin-1 (ETB) Despopoulos, Color Atlas of Physiology © 2003 Thieme Regulation Mediated by Endothelium endothelial-derived relaxing factor (EDRF) - NO Guyton and Hall. Textbook of Medical Physiology, 11th edition 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 Mediated by Endothelium endothelins ❖ polypeptides synthesized by endothelial cells (ET-1, ET-2, ET-3) ❖ 2 endothelin receptors: ETA - specific for ET-1, in many tissue vessels, -> vasoconstriction ETB - ET-1 to ET-3, function? ❖ ET-1 - one of the most potent vasoconstrictive substances ❖ the exact physiological role not known ❖ restricts bleeding, play a role in closing ductus arteriosus at birth egulation of Blood Flow - Loca Serotonin (5-OH tryptamine) ❖vasoconstrictive effect • in a damaged tissue • direct local effect • released from thrombocytes ❖vasodilatory effect • in an undamaged tissue • through increased activity of NO synthase Other mechanisms ❖ temperature, ... ❖ damaged vessels ❖ specialized tissues (kidneys, brain, etc.) A. Acute seconds to minutes, but incomplete (about % of the desired effect) 1. Metabolic Autoregulation 2. Myogenic Autoregulation 3. Regulation Mediated by Endothelium B. Chronic hours, days to weeks, even months Chronic regulation Guyton and Hall. Textbook of Medical Physiology, 11th edition Especially important in case of the long-term change of metabolic demands of a tissue - to provide sufficient blood flow without circulation overload. Chronic regulation ❖ mediated by changes of the tissue vascularity ❖ the key role - lack of 02, also nutrients ❖ angiogenic or vascular growth factors - small peptides, best characterized: vascular endothelial growth factor (VEGF), fibroblast growth factor, and angiogenin ❖ fast in young individuals and in newly formed tissue Chronic regulation unstimulated muscle regularly stimulated muscle • * • • * f l • * * • * ■ ... -1 A * \ * Iprn -*-- * * * • • t • • • • *■ ...... v% Guyton and Hall - Textbook of Medical Physiology (12th edition)