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