Local Regulation of Blood Flow L29 Notes PDF

L29 Local Regulation of Blood Flow ILOs By the end of this lecture, students will be able to 1. Interpret the autoregulatory mechanisms of arterioles. 2. Relate the autoregulation of the arteriolar diameter to the blood flow. 3. Differentiate between the mechanisms of metabolic autoregulation of blo...

L29 Local Regulation of Blood Flow ILOs By the end of this lecture, students will be able to 1. Interpret the autoregulatory mechanisms of arterioles. 2. Relate the autoregulation of the arteriolar diameter to the blood flow. 3. Differentiate between the mechanisms of metabolic autoregulation of blood flow. 4. Correlate the vasoactive substances to the arteriolar diameter and blood flow. Introduction: Blood flow is the quantity of blood that passes a point in the circulatory system per unit time. Normally, blood flow in the systemic circulation equals the cardiac output of the left ventricle which in turn equals the total tissue blood flow. Factors determining the blood flow: Blood flow in a vessel (F) is directly proportional to the pressure gradient between the beginning and the end of the vessel (P1 – P2 = ∆ P). And F is inversely proportional to the resistance which the blood meets in the vessel (R). So, F = ∆ P R Resistance (R) is directly proportional to the viscosity and the length of the vessel, and it is inversely proportional to the fourth power of the radius of the vessel (r4) R α Viscosity X Length r4 1- Blood viscosity: Blood viscosity is about 5 times as H2O and is caused by: a) Hematocrit: Increased Hematocrit increases the viscosity leading to increased R and thus F decreases. Decreased Hematocrit has an opposite effect. 1 b) Concentration of plasma proteins: The viscosity of plasma is about 1.5 times that of H2O (a less important effect on blood viscosity than the hematocrit). Accordingly, to correct arterial blood pressure in hemorrhage blood transfusion is used instead of saline. 2- Diameter of the vessel: R α 1/r4 Increased diameter (vasodilation by decreased vasomotor tone) decreases the resistance, and vasoconstriction increases the resistance. * The main site of peripheral resistance (PR) is the arterioles (because they are narrow and connected in series). So, F α r4 * Physiologically: Small changes in arteriolar diameter leads to relatively big changes in flow, so blood can be diverted to match the metabolic needs of the tissues. * Pathologically: Mild narrowing produced by, e.g., atherosclerosis results in large reductions in blood flow. Types of blood flow: 1- Streamline (Laminar) Flow: All the particles in the fluid are flowing parallel to the wall of the tube. However, they are not all moving at the same velocity. Those fluid particles in contact with the wall of the tube are theoretically stationary whilst those at the center (axis) of the tube are flowing fastest. Laminar blood flow helps eliminate energy losses. 2 2. Turbulent Flow: Changes in blood velocity turn streamline flow into turbulent flow. 3 Changes in the blood flow to the tissues aim at: - increasing the blood supply to active tissues. controlling heat loss from the body through the skin. maintaining the blood flow to the vital organs. Changes of blood flow can be achieved by: 1- Changing the cardiac output which changes the blood flow in the whole circulation. 2- Changing the diameter of blood vessels, especially the arterioles which controls the blood flow to the tissues locally. 4 Vascular smooth muscle contraction: Molecular mechanism of vascular smooth muscle contraction and of Vasoconstrictors: - RMP only ≈ - 40 mV - Stretch by blood Pressure opens ion channels leading to partial depolarization and partial contraction. This is called Bayliss Effect (Vascular smooth muscle responds to stretch by contracting). * Advantage of this partial contraction: Physiological mediators can cause further contraction or relaxation as appropriate. Stimulus-contraction coupling mechanism: 5 Main molecular mechanism of Vasodilators: 6 I. Local (Intrinsic) A- Endothelial or Platelets-mediated vasoactive substances - A mixture of compounds with vasodilator or vasoconstrictor effect. - They play an important role in physiological and pathological conditions. Vasodilators include: 1- Nitric Oxide (NO) [Endothelium-derived Relaxing Factor (EDRF)]. 2- Endothelium Derived Hyperpolarizing Factor (EDHF). 3- Prostacyclin (PGI2). Vasoconstrictors include: 4- Thromboxane A2 and prostaglandin H2. 5- Endothelins (ET-1, ET-2, ET-3). Vasodilators: NO: - Has a short physiological half-life (a few seconds). - Must be generated continuously and the single most important trigger is increased shear stress on the blood vessel wall by increased blood velocity. - Contributes to short-term changes in blood vessel diameter. - Main site of action is on large diameter arterioles. Effect of vasodilator drugs (e.g., Nitrovasodilators) on the heart: - On capacitance vessels they decrease the venous return, thus decreasing the Preload. - On resistance vessels they decrease the arterial blood pressure, thus decreasing the Afterload. Both two effects decrease the cardiac metabolism and the O2 demand and may relief coronary spasm. 7 Vasoconstrictors: Endothelins (ET-1, 2 & 3): Endothelin-1 is the most potent and causes very strong vasoconstriction (more in veins). - Prostaglandins: Platelets release Thromboxane A2 which causes vasoconstriction (and increased platelet aggregation). - Endothelium releases Prostacyclin (PGI2) which causes vasodilation (and decreased platelet aggregation). * Their balance maintains a localized clot without excessive extension which maintains the blood flow. 8 B- Autoregulation The blood flow to some tissues is adjusted to their metabolic activities, also, it remains almost constant in spite any change in arterial blood pressure (flow autoregulation). Autoregulation of blood flow is explained by the following mechanisms: 1) Myogenic Autoregulation: “The intrinsic contractile response of vascular smooth muscle to stretch” e.g., increased arterial blood pressure increases the blood flow initially, but also causes stretch of wall of arterioles which results in contraction of the smooth muscles in their wall leading to vasoconstriction and decreased blood flow back to normal. 2) Metabolic Autoregulation: Increased tissue metabolism results in relaxation of arterioles & precapillary sphincters leading to increased local blood flow (& vice vera). 9 Mechanism of metabolic autoregulation: Increased tissue metabolism leads to: 1- Accumulation of Vasodilator Metabolites as: CO2 (especially in Brain and Skin). H+ K+ Lactic acid (in skeletal muscle). Adenosine (in muscle), mediated by ATP-sensitive K channels: on the endothelial cells increasing NO and on underlying smooth muscle. Histamine (in injured tissues). Local changes in ISF osmolarity. It is thought that H+, rather than CO2 directly, is the effective agent. Increased [H+] ions leads to opening of ATP-sensitive K+ channels on smooth muscle causing hyperpolarization and relaxation which increases the blood flow. 2- Decreased O2 i.e. Hypoxia (and decreased other nutrients needed to maintain vascular smooth muscle contraction), (O2 demand mechanism). Hypoxia leads to: - Opening ATP-sensitive K+ channels causing vasodilatation. - Release of vasodilator prostaglandins. [EXCEPT in the pulmonary circulation, where decreased O2 in alveolar air causes constriction of the nearby pulmonary vessels]. 3- Increased temperature. __________________________________________ 1- Noble A, Johnson R, Thomas A, and Bass P. The Cardiovascular System, BASIC SCIENCE AND CLINICAL CONDITIONS, 2nd ED. Elsevier Limited; 2010, Chapters 9: 99- 106. 2-Hall JE. Guyton and Hall Textbook of Medical Physiology, 14th. Ed. Elsevier Saunders; 2021, Chapter 17. 10