Cardiovascular Physiology （心血管生理学） Qiang XIA (夏强), MD & PhD Department of Physiology Room C518, Block C, Research Building, School of Medicine Tel: 88208252 Email: email@example.com Vascular Physiology（血管生理学） Lecture Outline • • • • • • Functional parts of blood vessels Hemodynamics Arterial blood pressure Microcirculation Venous pressure and venous return The lymphatic system Functional parts of blood vessels Elastic vessels (Windkessel vessels) （弹性血管） Distribution vessels（分布血管） Resistance vessels (Precapillary resistance vessels)（阻力血管） Exchange vessels（交换血管） Shunt vessels（短路血管） Capacitance vessels（容量血管） Hemodynamics（血流动力学） • Blood flow Q= DP/R = (P1-P2)/R Q= PA/R Q: cardiac output, 5 L/min R: total peripheral resistance PA: aortic pressure Resistance of blood flow Poiseuille Law: Q=pDPr4/8hL h: viscosity r: radius of the vessel L: length of the vessel R= 8hL/pr4 Q= DP/R Jean Louis Marie Poiseuille \pwä-'zəi\ (April 22, 1799 - December 26, 1869) was a French physician and physiologist. Poiseuille was born in Paris, France. From 1815 to 1816 he studied at the École Polytechnique in Paris. He was trained in physics and mathematics. In 1828 he earned his D.Sc. degree with a dissertation entitled Recherches sur la force du coeur aortique. He was interested in the flow of human blood in narrow tubes. r: main determinant of blood flow Arterial blood pressure（动脉血压） Arteries Blood pressure measurement 1. Direct (invasive) measurement technique 2. Indirect (non-invasive) measurement technique Systolic pressure (SP，收缩压): the maximum arterial pressure reached during peak ventricular ejection Diastolic pressure (DP，舒张压): the minimum arterial pressure just before ventricular ejection begins Pulse pressure (PP，脉压): the difference between SP and DP Mean arterial pressure (MAP， 平均动脉压): the average pressure in the cardiac cycle (=DP+1/3PP) Mean arterial pressure (MAP) To estimate systolic and diastolic pressures, pressure is released from an inflatable cuff on the upper arm while listening as blood flow returns to the lower arm. Click here to play the Sphygmomanometry Flash Animation Classification of blood pressure for adults age 18 years and older Blood Pressure Classification Chart Category Systolic (mm Hg) Diastolic (mm Hg) Normal Lower than 120 Lower than 80 Prehypertension 120 - 139 80 - 89 Stage 1 140-159 90-99 Stage 2 160 or higher 100 or higher Hypertension Adapted from The Seventh Report on the joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), NIH Publication No. 03-5233, May 2003 The classification chart is based on adults, aged 18 and older, who are not taking high blood pressure medicines and who are not acutely ill. If systolic and diastolic measurements fall into different categories, the higher category should be used to classify the person's blood pressure status. Factors affecting arterial blood pressure • Stroke volume • Heart rate • Peripheral resistance • Elastic vessels • Blood volume Ventricular ejection Q= PA/R Q: cardiac output (CO) R: total peripheral resistance (SVR) PA: aortic pressure (MAP) MAP = CO SVR 3 1 2 4 5 The blood moved in a single heart contraction stretches out the arteries, so that their recoil continues to push on the blood, keeping it moving during diastole. Movement of blood into and out of the arteries during the cardiac cycle Arterial pulse（动脉脉搏） In response to the pulsatile contraction of the heart: pulses of pressure move throughout the vasculature, decreasing in amplitude with distance Arterial pulse recorded in different vessels Arterial pulse recorded under different conditions Microcirculation（微循环） Function: Transfer of substances between blood & the tissues Structure of microcirculation A-V shunt 3 pathways • Circuitous channel (Nutritional channel)（营 养通路） 2 1 3 A-V shunt 4 5 • Thoroughfare channel（直捷通路） 2 1 3 A-V shunt 4 5 • Arteriovenous shunt (A-V shunt)（动-静脉短路） 2 1 3 A-V shunt 4 5 • Blood travels from artery to arteriole to capillary to venule to vein Arterioles（微动脉） Two major roles: • To be responsible for determining the relative blood flow in individual organs at any given MAP • To be a major factor in determining MAP Dynamic adjustments in the blood distribution to the organs is accomplished by relaxation and contraction of circular smooth muscle in the arterioles. Click here to play the Arteriolar Radius & Blood Flow Flash Animation Click here to play the Arteriolar Resistance & BP Flash Animation Local Control of Blood Flow • The mechanism independent of nerves or hormones by which organs and tissues alter their own arteriolar resistances, thereby self-regulating their blood flows – Active hyperemia（主动充血） – Flow autoregulation（血流自身调节） – Reactive hyperemia（反应性充血） – Local response to injury（对损伤的局部反应） Local control of organ blood flow Active hyperemia and flow autoregulation differ in their cause but both result in the production of the same local signals that provoke vasodilation. • Reactive hyperemia – When an organ or tissue has had its blood supply completely occluded, a profound transient increase in its blood flow occurs as soon as the occlusion is released • Response to injury – Tissue injury causes a variety of substances to be released locally from cells or generated from plasma precursors. These substances make arteriolar smooth muscle relax and cause vasodilation in an injured area Extrinsic Control • Sympathetic nerves（交感神经） • Parasympathetic nerves（副交感神经） • Noncholinergic, nonradrenergic autonomic neurons (NO or other noncholinergic vasodilator substances)（NANC） • Hormones (epinephrine, angiotensin II, vasopressin, atrial natriuretic peptide) Sympathetic stimulation of alpha-adrenergic receptors cause vasoconstriction to decrease blood flow to that location. Sympathetic stimulation of beta-adrenergic receptors lead to vasodilation to cause an increase in blood flow to that location. Renin-angiotensin system（肾素-血管紧张素系统） ANGII can be produced directly by conversion of angiotensinogen by the tissue plasminogen activator (tPA), cathepsin G and tonin or by hydrolysis of angiotensin I by chymase and cathepsin G. CAGE = chymostatin-sensitive angiotensin II-generating enzyme Robert Toto & Biff F. Palmer. Am J Nephrol 2008;28:372–380 Vasopressin（血管升压素） Endothelium-derived vasoactive substances •Vasodilator factors •PGI2 – prostacyclin（前列环素） •EDRF (endothelium-derived relaxing factor, nitric oxide) •EDHF (endothelium-dependent hyperpolarizing factor) The 1998 Nobel Prize in Physiology or Medicine Nitric oxide as a signaling molecule in the cardiovascular system Louis J Ignarro Ferid Murad Robert F Furchgott Sildenafil, the prototypical PDE5 inhibitor A phosphodiesterase type 5 inhibitor, often shortened to PDE5 inhibitor, is a drug used to block the degradative action of phosphodiesterase type 5 on cyclic GMP in the smooth muscle cells lining the blood vessels supplying the corpus cavernosum of the penis. These drugs are used in the treatment of erectile dysfunction, and were the first effective oral treatment available for the condition. Because PDE5 is also present in the arterial wall smooth muscle within the lungs, PDE5 inhibitors have also been explored for the treatment of pulmonary hypertension, a disease in which blood vessels in the lungs become abnormally narrow. •Vasoconstrictor factors – Endothelin-1（内皮素-1） Major factors affecting arteriolar radius Diversity among signals that influence contraction/relaxation in vascular circular smooth muscle implies a diversity of receptors and transduction mechanisms. Capillaries（毛细血管） • Main function: Exchange of nutrients and metabolic end products Capillaries lack smooth muscle, but contraction/relaxation of circular smooth muscle in upstream metarterioles and precapillary sphincters determine the volume of blood each capillary receives. Capillary walls are a single endothelial cell in thickness. The capillary is the primary point exchange between the blood and the interstitial fluid (ISF). Intercellular clefts assist the exchange. Structure of capillary wall Structure of the capillary wall •Continuous: found in muscle, skin, lung, central nervous system •Fenestrated: found in exocrine glands, renal glomeruli, intestinal mucosa •Discontinuous: found in liver, spleen, bone marrow Relationship between total cross-sectional area and flow velocity Six balls in per minute mandates six balls out per minute. Therefore, the velocity of the balls in the smaller tubes is slower. There are many, many capillaries, each with slow-moving blood in it, resulting in adequate time and surface area for exchange between the capillary blood and the ISF. • Diffusion • Pinocytosis • Filtration and Reabsorption Movement of fluid and solutes out of the blood is called filtration. Filtration Absorption Movement of fluid and solutes into the blood is called absorption. Net filtration pressure (or Effective filtration pressure) EFP + Filtration EFP - Reabsorption Pc EFP Click here to play the Fluid Change Across Capillary Wall Flash Animation Effects of arteriolar vasodilation or vasoconstriction on capillary blood pressure Dynamic changes in vasodilation/vasoconstriction in the arterioles regulate downstream pressures and flow rates. Venous pressure and venous return （静脉血压与静脉回流） • Venous pressure – Peripheral venous pressure（外周静脉压）── the pressure in the peripheral veins – Central venous pressure (CVP，中心静脉压)── the pressure in the thoracic vena cava & the right atrium 4~12cmH2O Central venous pressure measurements were obtained for three astronauts (indicated by different colors). Notice the dramatic CVP changes that occurred during launch as well as when the astronauts arrived in space. Measurement of central venous pressure Jugular venous pressure is a clinical measure of central venous pressure. It is the height of the pulsating column of blood in the great veins draining into the right atrium and, in malaria, is a useful measure of over- or underhydration (hyper- or hypovolaemia). Jugular venous pressure is the vertical distance, measured in cm, between the venous pulsation in the neck and the sternal angle (junction of the second rib with the sternum) when the patient is propped up on pillows at 45 to the horizontal. In this position, the sternal angle marks the level of the right atrium. The height of the jugular venous pressure is normally 4–5 cm. In order to measure it, the patient should be made as comfortable and relaxed as possible. It is difficult or impossible to identify venous pulsation if the neck muscles are contracted. Try to achieve good (oblique) lighting of the neck. Look for the jugular venous pulse in the internal jugular vein or its external jugular tributaries on both sides of the neck with the patient's chin tilted up and slightly away from you. The following characteristics help to distinguish jugular venous pulsation from carotid arterial pulsation. The jugular venous pulse: •has two waves for every single carotid artery pulsation; make this comparison by gently palpating the carotid pulse on the opposite side of the neck; •falls with inspiration and rises with expiration (except where there is cardiac tamponade); •can be obliterated by pressing firmly but gently with the back of the index finger placed horizontally just above the clavicle at the root of the neck; •may be visible only when the patient is lying flat (in cases of hypovolaemia) or when the patient is sitting upright at 90 (for example, in severe congestive cardiac failure); •is usually impalpable. At rest, approx. 60% of the total blood volume is in the veins. Sympathetically mediated venoconstriction can substantially increase venous return to the heart. Determinants of venous pressure • Contraction of venous smooth muscle – Sympathetic neurons – Hormonal and paracrine vasodilators and vasoconstrictors • Skeletal muscle pump • Respiratory pump Venous valve Varicose vein（曲张静脉） Varicose vein great saphenous vein Venous flow is assisted by the skeletal muscle pump mechanism working in combination with one-way valves. Respiratory activity (Respiratory pump) Alterations in “venous return” alter end-diastolic volume (EDV); increased EDV directly increases stroke volume and cardiac output. The Lymphatic System （淋巴系统） • The lymphatic system is a network of small organs (lymph nodes) and tubes (lymphatic vessels) through which lymph flows Lymphatic fluid, formed by the slight mismatch between filtration and absorption in the capillaries, returns to the blood in the veins. Terminal lymphatics Lymphatic pump Relation between interstitial fluid pressure and lymph flow Significance of lymphatic return • Absorption of proteins • Transportation of fat and other nutrients • Balance between plasma and interstitial fluid • Protection Elephantiasis （象皮肿） Chronic, often extreme enlargement and hardening of cutaneous and subcutaneous tissue, especially of the legs and external genitals, resulting from lymphatic obstruction and usually caused by infestation of the lymph glands and vessels with a filarial worm. Elephantiasis Also known as lymphatic filariasis, this condition occurs when parasitic worms (any of several types of filaria worms) infest the lymphatic system. The filaria are transmitted by mosquitoes to the blood and can build a population in the lymph nodes, blocking fluid drainage from arms, legs, genitals, or breasts. It is called elephantiasis (literally, "elephant condition") because in extreme cases, the arms and legs look like the limbs of an elephant. Elephantiasis affects over a 100 million people around the world. However, most cases are not as extreme as in this photo! A summary of dynamic changes in MAP and TPR. Blood loss causes a reduction in MAP, which, if left unchecked, would result in rapid and irreversible damage to the brain and the heart. The End.