CV Physiology (2024) PDF

의료인공지능 융합인재양성 사업 Cardiovascular system - 심혈관계 생리 - Dept of Physiology Ajou University School of Medicine Contents 1. Overview of Circulation 2. Elements of Cardiac Function  Anatomy of the Heart  Electrical Properties of th...

의료인공지능 융합인재양성 사업 Cardiovascular system - 심혈관계 생리 - Dept of Physiology Ajou University School of Medicine Contents 1. Overview of Circulation 2. Elements of Cardiac Function  Anatomy of the Heart  Electrical Properties of the Heart  Electrocardiography (ECG)  Cardiac Pump (Mechanical Activity of Heart) 3. Vascular System Overview of Circulation  CVS-Introduction Introduction  Cardiovascular system (심혈관계 心血管系) - circulatory system (순환계): composed of heart and vascular system  Discovery of the circulation - William Harvey (1578-1657) - The circulation of the blood is caused by pumping of the heart. “ the foundation for the modern concepts of the circulation” 1. Function of Cardiovascular System 1) Blood circulation (혈액순환) - transfer O2 and nutrients to peripheral tissues and cells, and remove metabolic wastes (CO2 and other wastes)  Heart - blood pump: generates pressure for circulation (blood pressure) - sensory and endocrine function: regulates blood volume and blood pressure  Blood vessels - conduit for blood - sensory and effector organs: controls blood pressure and distribution of blood  Microcirculation (미소순환계) - place for material exchange: where the purpose of blood circulation is performed 2) Homeostatic functions (항상성 유지) - regulation of body temperature, hormone transport - regulatory role for altered physiological condition e.g. hemorrhage, exercise, changes in posture 2. Components of Cardiovascular System (심혈관계의 구성) Heart Vascular system Blood and Lymph 1) Heart - two pumps in series (직렬로 연결된 두 개의 펌프)  right heart: right atrium (우심방), right ventricle (우심실)  left heart: left atrium (좌심방), left ventricle (좌심실) 2) Vascular system - closed system (폐쇄 시스템) arterial vessel system (동맥계): aorta (대동맥), artery (동맥) arteriole (세동맥) venous vessel system (정맥계): vena cava (대정맥), vein (정맥) venule (세정맥) microcirculation system (미소순환계): capillary (모세혈관) lymph system (림프계) 3. Circulation System (순환회로) 1) Series Flow through the CV System (심혈관계를 통한 직렬혈류) - left heart → systemic circulation → right heart → pulmonary circulation → left heart  Systemic Circulation (체순환) - left ventricle  artery system  capillaries  vein system  right atrium - high pressure system: [arterial pressure: 120/80 mmHg (systole/diastole)]  Pulmonary Circulation (폐순환) - right ventricle  pulmonary arteries  capillaries (lungs)  pulmonary veins  left atrium - low pressure system: [pulmonary arterial pressure: 25/8 mmHg (systole/diastole)] 2) Parallel Flow within the Systemic Circulation (체순환에서의 병렬혈류) - each organ receives fully oxygenated blood - blood flow to organs can be independently regulated Series flow: Systemic circulation, Pulmonary circulation Parallel flow except GI-liver, Kidneys Elements of Cardiac Function 1. Anatomy of the Heart 2. Electrical Properties of the Heart 3. ECG (Electrocardiography) 4. Cardiac Pump 1. Anatomy of the Heart (심장의 구조)  Location and External View (심장의 위치 및 외관)  Atrium (심방) and Ventricles (심실): 4 Cardiac Chambers (심장격실) The walls of the heart Myocardium, endocardium, pericardium 심막강 심내막 심근층 심외막 Pericardium (심낭) 1) Visceral pericardium (분비층) = epicardium (심외막) 2) Parietal pericardium (벽쪽심장막) 3) Pericardial cavity (심막강: 심낭액으로 채워져 있음) 4) Fibrous pericardium (외부섬유성 덮개)  Coronary Vessels (관상혈관 冠狀血管) - coronary artery (관상동맥) - coronary vein (관상정맥)  reflux to the right atrium (우심방)  Heart Valves (심장판막) - located at the entrance and exit of each ventricle 1) Atrioventricular valves (AV, 방실판막) - between the atria and ventricles  tricuspid valve (삼첨판): right atrioventricular (AV) valve  bicuspid valve (이첨판) (= mitral valve, 승모판): left atrioventricular (AV) valve 2) Semilunar valves (반월판막) - between ventricles and major arteries  aortic valve (대동맥판= semilunar valve, 반월판)  pulmonary valve (폐동맥판)  diffusion 2. Heart Heart valves Valves (심장판막) - one-way flap valves (단방향 밸브) - opening and closing of valve (판막 개폐): passive process due to pressure difference in and out of the valve (판막 내외의 압력차 ) 2. Electrical Properties of the Heart (심장의 전기적 성질) 1) Electrical Activity of Cardiac Cells (심근의 전기적 활성) 2) Conduction Pathway (흥분 전도계) 3) Cardiac Action Potential (심근의 활동전압)  Fast-response Action Potential  Slow-response Action Potential 4) Cardiac Excitability (심근의 흥분성)  Cardiac Refractory Period (심근의 불응기) 1) Electrical Activity of Cardiac Muscle (1) Types of cardiac muscle cells - cardiac muscle cell: striated muscle (횡문근), involuntary muscle (불수의근) Contractile cells: working myocardium - most of the atrial, ventricular tissue - action potential generates muscle contraction and pressure Conducting (Autorhythmic) cells (전도 (자율박동) 세포): composed of pacemaker (박동원) and conduction fiber (전도섬유) - automatically generate AP(활동전위) and propagate to all over the heart - neither contract nor generate power - sinoatrial (SA) node, atrioventricular (AV) node, bundles of His, bundle branches, Purkinje fiber  Autorhythmic cell: 자동율동세포  AP: action potential, 활동전위  SA node: 동방결절  AV node: 방실결절  Pacemaker: 박동원, 심박조율기, 심장박동기 (2) Functional Sincytium (기능적 합포체 機能的 合胞體) Cardiac action potential (AP) - generated in SA node (동방결절) - gap junctions (간극결합): rapid propagation of action potential from pacemaker to conduction fiber and contractile muscle Functional syncytium (기능적 합포체 機能的 合胞體) - a collection of cells that function as one unit - atrial syncytium ( 심 방 합 포 체 ): right and left atrium are electrically united → concurrent contraction of both atria - ventricular syncytium (심실합포체): right and left ventricle are electrically united → concurrent contraction of both ventricles 2) Conduction Pathway (흥분 전도계)  Automaticity (자동성)  Rhythmicity (규칙성)  Pacemaker (박동원)  SA node → atrial excitation ↓ AV node → AV bundle → Purkinje fiber → ventricular excitation (1) Generation of pacemaker potential  Sinoatrial node (SA node; 동방결절) - location: sinus venosus (정맥동) - generates normal pacemaker potential - P cells: generates pacemaker potential - rate: normally 70 beats/min - myogenic rhythmicity (근원성 박동) (independent of nervous system) (2) Atrial conduction (심방전도) - conduction velocity: 1m/sec - conduction to left atrium: anterior interatrial myocardial band (or Bachmann’s bundle) * Functional syncytium: atrial syncytium - conduction to AV node: internodal pathways (3) Atrioventricular Conduction (방실전도)  Atrioventricular node (AV node; 방실결절) - atrial conduction to AV node: three tracts (the anterior, middle, and posterior internodal pathways) - the only pathway for excitation to proceed from atria to ventricle; electrical insulation between atrium and ventricle: atrioventricular ring (섬유성 방실환) - AV nodal delay: ensures that atrial contraction is completed before ventricular contraction begins (time for ventricular filling) (4) Ventricular conduction  His bundle - Right and Left bundle branch  Purkinje fiber - ramify throughout the subendocardial layer of both ventricles - highest conduction velocity: 2-4 m/sec 3) Cardiac Action Potential (1) Types of Cardiac Fiber (based on Electrical Characteristics) (심근세포의 전기적 특성에 따른 분류) - Fast Response Fibers (속섬유): more negative RMP, fast generation of AP, fast conduction velocity - Slow Response Fibers (완섬유): less negative RMP, slow generation of AP, slow conduction velocity * RMP: resting membrane potential (안정막전압) (2) Fast Response Action Potential (속섬유의 활동전압) - ventricles, atria, Purkinje fibers, His bundle fibers - more negative RMP, fast generation of AP, fast conduction velocity (a large-amplitude, steep upstroke and greater overshoot (compared with slow response fiber)) - long duration of AP: 200 - 400 msec (ca. 100 times longer than skeletal muscle or nerve fiber)  The Phases of the AP (속섬유의 활동전압 단계) a. Phase 0 (rapid upstroke): rapid depolarization (빠른 탈분극): 1-2 msec - threshold potential (문턱전압): - 65mV (induced by the AP of adjacent cell) - Na+ fast channel  massive influx of Na+ (due to concentration gradient) * Tetrodotoxin: selective blocker for Na+ fast channel Brief Repolarization Depolarization b. Phase 1 (early repolarization, 조기재분극): brief repolarization  Plateau by K+ efflux through channels that conduct the transient outward  current, Ito c. Phase 2 (plateau): sustained depolarization (100-250 msec)   Repolarization - balanced between Ca2+의 influx and K+ efflux → delay in repolarization - L-type Ca2+ channel open   d. Phase 3: repolarization (재분극) - begins when K+ efflux > Ca2+ influx e. Phase 4: resting potential (안정막전위) (3) Slow Response Action Potential (완섬유의 활동전압) - Pacemaker potential (SA node, AV node) - myogenic rhythmicity: AP generation without neural innervation   - unstable RMP: less negative (-65 mV); threshold -40 mV - less steep upstroke (slow depolarization), no early  repolarization (phase 1). no sustained plateau The phases of the AP a. Phase 4: beginning depolarization: Na+ “leaking” through F-type (funny) channel; Ca2+ influx through T-type Ca2+ channel b. Phase 0: rapid depolarization; depolarization by L-type Ca2+, not Na+ channel “Ca2+ action potential” c. Phase 3: repolarization (by closing of Ca2+ channels and by reopening of K+ channel)  Pacemaker (심박조율기) (a) SA node: normal pacemaker (정상 심박조율기) - AP is generated by the fastest diastolic depolarization (b) Ectopic pacemaker (이소성 심박조율기): AV node, Bundle of His and Purkinje fibers; latent pacemakers (have capacity for spontaneous impluse); in normal condition, the capacity of the latent pacemaker to spontaneous depolarize is suppressed  overdrive suppression * Intrinsic Firing Rate of SA Node & Latent Pacemakers  SA node: 70 – 80 /min  AV node: 40 – 60 /min  His - Purkinje fibers: 15 – 40 /min * Pacemaker shift (4) Restoration of Ionic Concentration (이온 농도의 원상회복) - increased cytosolic [Na+]and [Ca2+] during AP generation are restored as follows; Na+: efflux to the outside of the cell * Na+/K+-ATPase (Na+-K+ pump): 3 Na+ for 2 K+ Ca2+: most of Ca2+ are reuptaken in SR (intracellular Ca2+ storage) by Ca-pump; remaining Ca2+ are excluded to the outside of the cell by Na+/Ca2+ exchanger (exchange 3 Na+ for 1 Ca2+) Two Main Types of Cardiac AP Fiber type Fast response type Slow response type Purkinje fibers sinoatrial(SA) node & Location atrial and ventricular fibers atrioventricular(AV) node RMP -90 mV -65 mV Threshold -60 mV -20 mV potential (Na+ channel open) (Ca2+channel open) Upstroke Spike (1-2 msec) less steep slope (100 msec) 1-4 m/sec: conducting fibers Conduction 0.01-0.05m/sec in SA and AV 0.3-1.0 m/sec: myocardial velocity nodes cells inhibited by Na+ channel inhibited by Ca2+antagonists Drug effects antagonists (tetrodotoxin) (verapamil, diltiazem) 3) Cardiac Excitability (심근의 흥분성) (1) Excitation-Contraction Coupling (흥분-수축 연결) a) contraction begins ca.10 ms after electric excitement (depolarization) (cf. skeletal muscle: ca. 2 ms) b) AP duration muscle contraction time are mostly overlaps. 3) Cardiac Excitability (심근의 흥분성) (2) Cardiac Refractory Period (심근의 불응기) - due to inactivation (불활성화) of Na+ channel a) depolarized cardiac cells are not re-excited until the middle of the repolarization period. absolute refractory period (절대불응기: ARP; Effective refractory period: ERP): ca. 200 ms - inactivation of Na+ channel → does not open; cannot generate another AP relative refractory period (상대불응기; RRP): 약 50-100 ms - inactivated Na+ channel begins to return to closed state → can generate another AP (require larger depolarization than ordinary one) b) Physiological significance of cardiac refractory period - total refractory period (총불응기) is longer than total AV conduction time total conduction time (=220 msec) 〈 ERP (=200 msec) + RRP (=100 msec)  prevents recycling of excitation (흥분의 재순환)  guarantee the cycle of atrial contraction - ventricular contraction (ensuring sufficient blood filling time) - tetanic contraction (심근의 강축) does not occur Elements of Cardiac Function 1.Anatomy of the Heart 2. Electrical Properties of the Heart 3. Electrocardiography (ECG) 4. Cardiac Pump  Einthoven’s triangle Willem Einthoven, Dutch (1860-1927) 1903 ECG recording 1924 Nobel Prize As the heart beats, action potentials on the heart cause an electrical signal on the body surface. ECG Waves and Complexes As the heart beats, action potentials on the heart cause an electrical signal on the body surface. PR interval: Conduction through the small AV node is associated with virtually no electrical signal on the skin QRS is large because the ventricular mass is large. QRS is short because conduction over the ventricles is very fast ECG Intervals and Segments - Intervals (간격) include the waves, segments (분절) do not. P-R interval - from the onset of the P wave to the onset of the QRS complex - normally 0.12 - 0.21 sec - atrioventricular conduction time including the AV nodal delay (방실전도시간) P-R segment - from the end of the P wave to the onset of the QRS complex = AV nodal delay - allow filling of ventricles (심실 혈액충만 시간 확보) S-T segment - from the j-point to the onset of the T-wave - beginning of ventricular repolarization (AP의 phase 2에 해당) Q-T interval - from the onset of the QRS complex to the end of the T wave - duration of electrical systole (전기적 수축시간 ) R-R interval Heart Rate (심박수, HR) = 60/R-R interval (sec) Cardiac Dysrhythmia (Arrhythmia, 不整脈) - an irregular heartbeat: too slow or too fast - Symptoms: palpitation (심계항진) or feels like heartbeat stops. lightheadedness (가벼운 현기증), shortness of breath, chest pain. may lead to cardiac arrest (심장마비)  Tachycardia vs bradycardia Tachycardia: 빈맥; Bradycardia: 서맥; Flutter: 조동; Fibrillation: 세동 Cardiac Dysrhythmia (Arrhythmia) - Due to disturbances of either impulse propagation or impulse initiation  Altered Sinoatrial Rhythm  AV conduction blocks  Ectopic tachycardia  Premature depolarization  Fibrillation (세동) - an irregular contraction that is entirely ineffectual in propelling blood.  Atrial fibrillation (심방세동)  Ventricular fibrillation (심실세동)  Defibrillator (제세동기) Defibrillator Fig-AP in Nerve, Muscle, Heart Elements of Cardiac Function 1.Anatomy of the Heart 2. Electrical Properties of the Heart 3. Electrocardiography (ECG) 4. Cardiac Pump (Mechanical Activity of Heart) 1. Myocardial Cell Structure (심근세포의 구조)  Sarcomeres( 근절): contractile IV. Mechanical Activityunit myofibrils (근의 수축단위) of Heart of the - thick filaments (myosin) - thin filaments (actin, tropomyosin and troponin)  T- tubules (transverse tubule): continuations of the sarcolemma (근세포막이 이어진 구조) - intrude into the cytosol at Z line of sarcomere (근절) - conduct AP into the inside of the cell  Sarcoplasmic reticulum - contain high concentrations of Ca2+ (Ca2+ storage) 2. Systole Phase (수축기) 1) Excitation-Contraction Coupling (흥분-수축 연결)  contraction begins ca.10ms after electric excitement (depolarization) (cf. skeletal muscle: ca. 2 ms)  AP duration and muscle contraction time are mostly overlaps  increase of heart rate → shortening AP duration and muscle contraction time time 2) Excitation-Contraction Coupling Process (흥분-수축 연결 과정) AP moves along the surface of the cell membrane to T-tubule  Ca2+ influx via L-type calcium channel  this Ca2+ influx causes a small increase in cytosolic Ca2+ concentration (locally)  not sufficient to induce contraction → ac as trigger (= trigger Ca2+)  this initial small increase in Ca2+ is detected by ryanodine receptors in the membrane of SR  causes release of Ca2+ from SR to cytosol (Calcium-induced calcium release)  muscle contracts 3. Diastole Phase (이완기) 1) Reduction of cytosolic Ca2+ concentration (세포내 Ca2+ 농도 감소)  Re-accumulation of Ca2+ in the SR (SR내로의 재축적 ) - SERCA (Sarco/endoplasmic reticulum Ca2+-ATPase or SR Ca2+-ATPase) - Phospholamban (PLB) and calsequestrin b-adrenergic stimulation → cAMP-dependent protein kinase↑→ phosphorylation of PLB → reduced association between SERCA and PLB; Phospho-phospholamban stimulates Ca2+ pumps of the SR  Extrusion of Ca2+ from the cell (세포외 배출 ) - Ca2+ pump - Na+- Ca2+ exchanger (1 Ca2+ for 3 Na+) x Excitation-Contraction Coupling 4. Myocardial Contractility, Inotropy (심근의 수축력) - intrinsic ability of muscle fibers to generate tension (장력= to contract) at a given muscle strength (= end- diastolic volume, 확장말기용적) - degree of tension generation: depends on cytosolic Ca2+ concentration and muscle length (cross-bridge) 1) Cytosolic Ca2+ concentration - directly related with cytosolic Ca2+ concentration  Increasing contractility (수축력 증대) - sympathetic stimulation (교감신경자극) - hypercalcemia (고칼슘혈증, [Ca2+]ECF)  [Ca2+ ]ICF - Inotropic agent (cardiac glycosides)  Decreasing contractility (수축력 감소) - parasympathetic stimulation (부교감신경 자극) - hyponatremia (저나트륨혈증, [Na+]ECF)  Na+ gradient  weak AP - Ca2+ channel antagonists 2) Frank-Starling relationship - length-tension relationship. ; stroke volume (1회 박출량) and cardiac output (심박출량) of the heart increases in response to an increase in the volume of filling (심실충만도 = ventricular end-diastolic volume, 확장말기용적). Effect of Cardiac Glycosides on Contractility  Cardiac glycoside: digitalis, digitoxin, ouabain - positive inotropic effect - inhibition of Na+-K+ ATPase  Less Na+ is pumped out  [Na+]i (Na+-accumulation in cytosol)  Na+- Ca2+ exchange decreases  Less Ca2+ is pumped out of the cell  [Ca2+]i contractility Foxglove Lily of the valley Milkweed Oleander Monarch butterfly Viceroy 5. Cardiac Cycle (심장주기)  Cardiac cycle (심장주기) ; systole (수축기) and diastole (이완기)  ventricular filling (심실충만)  atrial contraction (심방수축)  isovolumic contraction (등용성수축)  ventricular ejection (심실박출)  isovolumic relaxation (등용성이완) 1) Ventricular Systole (심실수축기) - Ventricular Systole: isovolumic contraction (등용성수축) and ejection phase (박출기); Q-T interval (1) Isovolumic contraction phase (등용성수축기) - begin right after QRS complex - initial conditions prior to systole Isovolumic phase · ventricular filling: ventricular end-diastolic volume (VEDV) · all the ventricular valves are closed (isovolumic) - only increase ventricular pressure in the above condition (isovolumic contraction) - Mitral (AV) valve closure: closed when ventricular pressure exceeds the atrial pressure → 1st. heart sound (2) Isotonic contraction phase (Ejection phase, 박출기) - rapid increase of ventricular wall tension  rapid increase of aortic pressure - Aortic valve-opening - Ventricular ejection (심실박출)  Rapid ejection phase (급속박출기) Close LV pressure > aortic pressure  Reduced ejection phase (감소박출기) LV pressure < aortic pressure continuous flow from LV to aorta Reduced ejection phase: LV pressure < aortic pressure continuous flow from LV to aorta 2) Ventricular Diastole (심실이완기) - Ventricular diastole: isovolumic relaxation (등용성이완기) and ventricular filling (심실충만기) (1) Isovolumic relaxation phase (등용성 이완기) - period between closure of aortic valve (대동맥판막; semilunar valve, 반달판막) and opening of AV valves - Aortic valve closure - 2nd heart sound (S2) - reducing ventricular pressure without ventricular volume change - Incisura (dicrotic notch, 절흔) (2) Ventricular filling phase (심실충만기) - Mitral valve-opening  Rapid filling phase  3rd heart sound (S3) - LV pressure < LA pressure: passive filling - rapid increase of ventricular volume, 80% full (blood inflow: atrium → ventricle)  Slow filling phase (diastasis, 분리기) Close - blood inflow from lung to left ventricle - peripheral blood (vein) inflows to right ventricle - gradual increase of atrial-, ventricular-pressure and ventricular volume  Atrial systole (심방수축) - completion of ventricular filling: rapid active filling 3) Heart Sound (심음) - Noises generated by the beating heart and the resultant flow of blood through it - Specifically, the sounds reflect the turbulence created when the heart valves snap shut (can be heard) Case Origin Remarks physiological AV valve (방실판막: mitral low frequency S1 Always audible V,create (does not tricuspid V) closure any sound) (낮은음) phsyiological aortic V closure high frequency S2 always audible pulmonary V closure (높은음) physiological rapid filling phase normal in - exercise gallop sound adolescence S3 - sinus tachycardia audible in childhood pathological - left vibration of the ventricle ventricular hypertrophy (심실의 진동) Pathological –congestive atrial contraction phase physiologically heart disease (울혈성 atrial sound inaudible S4 심장질환), ventricular dialation (심실확장) 6. Relationship between Heartbeat and Pressure-Volume (심장박동과 압력-용적관계) 1) Ventricular Pressure-Volume Loop (1) Isovolumic contraction (C  D) * Ventricular end diastolic volume (VEDV) (C) (2) Ventricular ejection (D  E  F) ; aortic valve open (D) Rapid ejection (D  E) Reduced ejection (E  F) * Ventricular End-systolic volume (VESV) (F) * stroke volume (D-F) (3) Isovolumic relaxation (F  A) ; aortic valve close (F) (4) Ventricular filling (A  B  C) ; mitral valve open (A) Rapid filling (A  B) Reduced filling (B  C) 2) Measures of cardiac function (심장기능의 측정) Stroke Volume (SV, 1회 박출량) Blood volume ejected from ventricle in one beat (= about 70 ml) SV = VEDV – VESV Ejection Fraction (EF, 박출계수) EF = SV/VEDV = (VEDV- VESV)/VEDV ESV EDV Cardiac Output (CO, 심박출량) Blood volume ejected from ventricle per minute CO (ml/min) = SV  HR = Venous return (5 L /min) Vascular System Vascular System (맥관계) Cardiovascular Circuitry Distribution of Blood Volume (Parallel- vs Serial-circuit)  Vascular System Histological Structures of Artery and Vein Hemodynamics (혈류역학)  I. Hemodynamics -- 1. 혈류량 Hemodynamics (혈류역학) 1. Flow Rate (혈류량, Q) - moving blood volume per unit time (단위시간 당 이동하는 혈액 용적) Q=V  A Q: Flow rate, V: mean velocity (평균 혈류속도), A : cross-sectional area (단면적) 2. Velocity of the Bloodstream (혈관별 총단면적과 혈류속도)  Cross-sectional area (단면적) capillaries > vein > aorta  Flow velocity in blood vessels (혈류속도) aorta > vein > capillary aorta: 20cm/s (pulsatile) large veins: 10cm/s capillary: 0.05cm/s (non-pulsatile) → Blood flow rate is the slowest in the capillaries with the largest total cross sectional area → allows time for adequate diffusion  2. 혈류-저항-압력 관 계 3. Relationship between Blood Flow Rate, Pressure and Resistance Q = ΔP / R < analogous to Ohm’s law : I = V / R > ΔPr4 Q≈  ΔP r4 8L Q: flow rate, R: resistance (저항), r: radius (혈관의 반경), : viscosity (혈액 점도), ΔP: pressure difference (혈관 양단의 압력차), L: vessel length (혈관 길이) Blood flow rate (혈류량, Q) is proportional to blood pressure → blood pressure (arterial pressure) is the driving force for blood circulation! ☞ For normal blood circulation, it is absolutely necessary to maintain arterial pressure at a physiological level. Blood flow rate is proportional to the forth power of the radius (r) (반경의 네제곱에 비례) ☞ 2 times increase of radius  16 times increase of blood flow rate ☞ Blood flow is highly sensitive to the change of the radius of blood vessel  controlling blood flow by varying the radius of the blood vessel is very useful in the blood vessel (ex, arteriole contraction, relaxation) Blood flow rate is inversely proportional to resistance Resistance to blood flow - causes: frictional components (friction between molecules or particles of the liquid, friction between liquid and the walls of tube (major factor)) - Resistance is inversely proportional to the forth power of radius (R  1 / r4) ☞ decrease of radius to 1/2  16 times increase of resistance ( blood flow rate is reduced to 1/16) - Pressure drop: The pressure decreased progressively as blood flows through each sequential component (due to energy loss caused by resistance)  2. 혈류-저항-압력 관 계 Q = ΔP / R < analogous to Ohm’s law : I = V / R > ΔPr4 Q≈  ΔP r4 8L R= ΔP/Q = 8ηL/πr4 R: hydraulic resistance Friction  Pressure Drop Atherosclerosis Once fluid begins to flow through the system, pressure falls with distance as energy is lost because of friction. (e.g. in the circulatory system)  The Arterial System (동맥계) 1. Arterial System and Function 2. Arterial Blood Pressure - Mean Arterial Pressure - Arterial Pulse Pressure - Peripheral Arterial Pressure Curves 3. Blood Pressure Measurement 4. Control of Blood Pressure - Determinants of Arterial Pressure - Regulation of Cardiac Output - Regulation by Baroreceptor and Cardioregulatory Center  II. 동맥계-1. 동맥의 기능 1. Arterial System and Function 1) Elastic arteries (Aorta and large branches) - blood perfusion (혈액관류기능) - contains lots of elastic tissue (elastin) - high compliance (확장성) and low resistance (pressure storage; small pressure drop) → stable blood flow → reducing heart-work 2) Artery (동맥) Fig-세동맥-SM-13-19-Ho - major hemoperfusion (주된 혈액 관류기능) - large smooth muscle content in especially periphery - relatively large diameter compared to the thickness of the vessel wall → low resistance → small pressure-drop 3) Arteriole (세동맥) - small internal diameter → high resistance → “resistance vessel (저항혈관)” → big pressure drop - large smooth muscle content: control of blood flow (혈류 조절의 기능) smooth muscle contraction and relaxation  changes in vessel diameter  changes in resistance  control of blood flow 2. Arterial Blood Pressure (동맥압) Systolic blood pressure (SBP, 수축기 동맥압, maximal) Diastolic blood pressure (DBP, 이완기 동맥압, minimal) Pulse pressure (PP, 맥압) = systolic pressure - diastolic pressure Mean arterial pressure (평균동맥압) - mean blood pressure during cardiac cycle - the main driving force for blood flow MAP = diastolic pressure + 1/3 pulse pressure = 1/3 x (systolic pressure + 2 diastolic pressure) e.g. SBP/DBP: 120/80, MAP = 80 mmHg + (1/3) 40 mmHg = 93 mmHg 3. Blood Pressure Measurement (혈압의 측정) - brachial artery (상완동맥) - Korotkoff’s sound 4. Control of Blood Pressure (혈압 조절) 1) Determinants of Pulse Pressure and Mean Arterial Pressure Physical factors (물리적 인자) PP  SV / C SV: stroke volume (1회 박출량); C: aortic compliance (동맥의 유순도) Physiological factors (생리적 인자) MAP = CO ☓ TPR * Total Peripheral resistance (TPR, 총말초저항) = sum of all the peripheral resistance Physical factors Physiological factors MAP 2) Regulation of Cardiac Output (1) Frank-Starling’ Principle - Cardiac output depends on preload (venous blood pressure, venous return)  Venous return (정맥환류량)   VEDV (확장말기용적)   stretch of cardiac muscle (심근의 신전)   cardiac contractility (심근의 수축성)   stroke volume (1회 박출량),  cardiac output (심박출량) - regulate cardiac output is equal to the venous return [Cardiac output = Venous return] Causes for increase in venous return (정맥환류량의 증가 요인) - increase of the total blood volume - redistribution of blood by venous compression/constriction Sympathetic Nervous System Parasympathetic Nervous System cardiac output (instead of ventricular stroke volume)) vs venous pressure (usually right atrial pressure) (2) Effect of Heart Rate on Cardiac Output CO= SV ☓ HR - Stroke volume is reversely proportional to heart rate increase of heart rate  shortening of diastole  ventricular filling ↓  preload ↓  Stroke volume ↓ - Changes in cardiac output is affected by heart rate 1. HR increase up to 100 - HR-increase effect is greater than SV-decrease - contractility ↑  Cardiac output ↑ 2. HR (100-200): no significant change in cardiac output 3. HR>200: SV-decrease effect exceeds HR-effect  Cardiac output ↓ 3) Autonomic Regulation of the Heart (자율신경에 의한 조절)  Sympathetic: innervated to both atria and ventricle  Parasympathetic: innervated to SA, AV nodes, and atria Fig-자율-SA-자극효과-f- 2-10-OP (1) Autonomic Effects on Heart (자율신경계의 작용) - Parasympathetic nerve (M receptor): sleep, rest, trained state; heart rate↓, contractility (심근수축력)↓, conduction velocity (전도속도)↓ - Sympathetic nerve (b receptor): stress, emotion, exercise; heart rate↑, contractility (심근수축력)↑, conduction velocity (전도속도)↑ Chronotropy: 변주기작용; heart rate Dromotropy: 변전도작용; 전도속도 Inotropy: 변력작용; 수축력 Lusitropy: 심실이완속도 Fig-자율-SA-자극효과-f- 2-10-OP  Dromotropism (변전도작용, changes in conduction velocity) - Sympathetic stimulation (교감신경 자극; NE) : Positive dromotropism (양성변전도작용, conduction velocity ↑) - Parasympatheic stimulation (부교감신경 자극; ACh) : Negative dromotropism (음성변전도작용, conduction velocity ↓) - effects on SA node: parasympathetic > sympathetic Ca2+ K+ adrenergic cholinergic b M G Gs AC Gi Increased + - negative + charge cyclic ATP AMP HYPERPOLARIZED INCREASED DECREASED PACEMAKER PACEMAKER ACTIVITY ACTIVITY Ca2+ channel K+ channel Autonomic effects on sinoatrial node  2. Baroreceptor 4) Regulation by Baroreceptor and Cardioregulatory Center Baroreceptor(압력수용기): arch of aorta (대동맥궁), carotid sinus (경동맥동) - Sensitively respond to changes in arterial pressure → induce the reflex for reciprocal changes of heart rate → prevent steep changes of blood pressure Baroreceptor MAP stretching Afferent nerve Cardiovascular Center (Medulla) Efferent nerve Sympathetic↓, Parasympathetic↑ HR↓, Cardiac contractility↓, Arteriole expansion↑ (skin, Venous expansion viscera, skeletal muscle) CO↓ TPR↓ MAP  Baroreceptors (압력수용기) Carotid sinus baroreceptors Aortic arch baroreceptors Location In the walls of the carotid sinus In the walls of the aortic arch Characteristics more sensitive than aortic sensitive to stretch pressure baroreceptor sensitive to pulsatile pressure Carotid sinus Aortic arch (경동맥동) (대동맥궁)  The Microcirculation System (미소순환계) Microcirculation System Transcapillary Exchange - Diffusion - Transcytosis - Filtration and Absorption Forces of Capillary Filtration Microcirculation System (미소순환계) Microcirculation Arterioles → capillaries → venules 〮 Metarteriole: 메타소동맥 〮 Precapillary sphincter: 모세혈관 전 괄약근 1. Characteristics of Capillaries (모세혈관의 특성) - diameter (평균직경): 7 μm - thin vessel wall without smooth muscle (1 μm) - blood flow velocity: 0.1 ~ 1 mm/sec - almost every cell in the body is within 20 μm of the capillaries - endothelial pore (내피세포공): passage of small molecules between (or on) capillary endothelial cells 2. Types of Capillaries (모세혈관의 종류) continuous capillaries: brain capillary (뇌모세혈관; BBB) fenestrated capillaries: renal capillary (신장모세혈관) discontinuous capillaries: liver, bone marrow 3. Transcapillary Exchange (모세혈관에서의 물질교환) 1) Diffusion (확산): depends on concentration gradient - O2, glucose: capillary  tissue; CO2, urea: tissue  capillary * low lipid solubility (e.g. Na+, K+, Cl-, glucose): transport via endothelial pore * high lipid solubility (e.g. O2, CO2, urea): pass directly through endothelial membrane 2) Transcytosis: vesicular transport of macromolecules from one side of a cell to the other 3) Filtration and absorption (여과 및 흡수) movement of plasma components through endothelial pore, fenestrae 4. Forces of Capillary Filtration (모세혈관 여과의 원동력)  Starling equilibrium (Starling’s hypothesis) - direction of water movement: determined by the difference of hydrostatic pressure (정수압) and oncotic pressure (교질삼투압) between the inside of the capillary and interstitial fluid - Hydrostatic pressure: at arterial end of capillary 32 mmHg, at venous end 15 mmHg; plasma oncotic pressure 25 mmHg → in case, plasma hydrostatic pressure > oncotic pressure, water moves into interstitium; in the opposite case, water moves into capillary - amounts of net filtration (순여과) and net absorption (순흡수) are balanced. (* In reality, net filtration is slightly higher than net absorption, which is removed by the lymphatic system) The Venous System (정맥계) The Venous System Characteristics of Venous Flow - Venous Pressure - Factors Promoting Venous Return 1. The Venous System (정맥계) 1) Function of Veins (정맥의 기능) (1) Venous return (정맥환류): blood flowing (reflux) into the heart through veins - passage through which blood from capillary returns to the heart (2) Capacitant vessel (용량혈관) - blood reservoir: contains about 64% of total blood volume Volume shift: storage capacity of the vein shifts to the arterial system by smooth muscle contraction (in case of bleeding..) 2. Characteristics of venous flow (정맥혈류의 특징) 1) Venous Pressure (정맥압) venule (세정맥) - right atrium (심장) pressure difference: 10 mmHg - venule (세정맥), small vein (소정맥):  10 mmHg - right atrium (우심방):  0 mmHg 2) Factors promoting venous return ((1) large diameter and very low resistance of vein (2) Venous valve (정맥 판막): one-way valve (일방성 판막) → prevent backflow of blood (3) Compression/decompression of veins  Muscle pump (근육 펌프): skeletal muscle contraction moves blood toward heart  Respiration (호흡운동): decent of diaphragm (횡격막) during inspiration → vein expansion due to reduced intrathoracic pressure; peritoneal contents compress abdominal vena cava → promote blood flow [abdominal vein (복부대정맥) → thoracic vein (흉부대정맥)]) 3. Effect of Postures to Blood Pressure (자세와 혈압) Arterial and venous pressure difference - driving force for blood flow Orthostatic hypotension (기립성저혈압, postral hypotension) - at standing position, venous return↓ → cardiac output↓ → blood pressure↓ (both systolic and diastole pressure↓) Major Factors determining peripheral venous pressure, venous return and stroke volume  Coronary Circulation (관상혈관순환) Coronary Circulation Acute Coronary Syndrome 1. Coronary Circulation (관상혈관 순환) 1) Coronary Vessel (관상혈관) Artery - Right coronary artery (우관상동맥): right atrium (우심방), right ventricle (우심실) - Left coronary artery (좌관상동맥): anterior descending and circumflex branches; left atrium (좌심방) and left ventricle (좌심실) Vein - Coronary sinus (관상정맥동) - Anterior coronary vein (앞심장정맥) 2) Coronary Circulation - coronary artery → capillary network → coronary vein (coronary sinus, anterior coronary vein)  right atrium 2. Acute Coronary Syndrome (급성 관상동맥 증후군) - a term that describes a range of conditions related to sudden, reduced blood flow to the heart (syndrome caused by narrowing or closure of the coronary arteries); include a heart attack and unstable angina Symptoms - chest pain (흉통) - nausea, sweating (오심, 발한) - angina pectoris (협심증): chest pain often radiating to the left arm Treatment Nitroglycerin Coronary Artery Sublingual Tablet : Bypass Graft (CABG) act in 1 -3 min Coronary Angioplasty Control of the Circulation (순환조절) Regulation of the Peripheral Circulation - Intrinsic or Local Control of Peripheral Blood Flow - Extrinsic Control of Peripheral Blood Flow Interplay of Central and Peripheral Factors in Control of the Circulation: Integrated Control - Hemorrhage - Exercise Regulation of the peripheral circulation (혈류의 조절) Intrinsic or local control of blood flow (국소인자에 의한 혈류조절)  Autoregulation and Myogenic regulation (자동조절 및 근원성 조절)  Endothelium-mediated regulation (혈관내피 인자에 의한 조절)  Metabolic Regulation (대사성 조절) Extrinsic control of blood flow (외인성인자에 의한 혈류조절)  Sympathetic vasoconstriction (교감신경 조절)  Parasympathetic neural influence (부교감신경조절)  Humoral factor (체액성인자) 1. Intrinsic or local control of blood flow (국소인자에 의한 혈류조절) - primary mechanism to regulate blood flow according to the metabolic needs of a tissue 1) Autoregulation and Myogenic regulation (자동조절 및 근원성 조절) - regulation to keep blood flow to tissue (organ) constant when arterial pressure changes - Increase in arterial pressure → transmural pressure (벽경유 압력) ↑ → stretching (elongation) of the arteriolar vessel wall → spontaneous depolarization (자발적 탈분극) → muscle contraction → inhibition of blood flow increase * Mechanism by which the stretching of blood vessel causes? → not well understood 2) Endothelium-mediated regulation (혈관내피인자에 의한 조절)  Local vasoactive mediators (국소적 혈관 작용제)  vasodilators (혈관확장제): nitric oxide (NO), histamine, PGI2, EDHF  vasoconstrictors (혈관수축제): angiotensin II, endothelin, EDCF EDHF: endothelial derived hyperpolarizing factor EDCF: endothelial derived constriction factor 3) Metaboilc Regulation (대사성 조절) (1) Active hyperemia (능동적 충혈) ; blood flow to a tissue (organ) is proportional to its metabolic activity * Local metabolic changes that influence arteriolar radius  O2↓  CO2↑  acid↑ (carbonic acid, lactic acid)  K+↑ (repeated action potentials)  Osmolarity↑ (by increased cellular metabolism)  Adenosine release  Prostaglandin releases (2) Reactive hyperemia (반응충혈) ; severe vascular relaxation during reperfusion (재관류) after blocking blood flow ex) arterial occlusion (동맥폐색)  O2 debt  more blood flow than before occlusion 2. Extrinsic control of blood flow (외인성인자에 의한 혈류조절) 1) Sympathetic vasoconstriction (교감신경조절) - Most arterioles are richly innervated by postganglionic sympathetic nerve (교감신경절후섬유) - Norepinephrine: secreted from postganglionic sympathetic nerve ending → acts on α receptor of arteriolar smooth muscle → muscle contraction → ↑PVR → ↑arterial pressure cf) coronary artery and cerebral artery: regulated mainly by local factors Vasomotor center of brain ( 연수 (medulla oblongata) 의 혈관운동중추 ): cerebrospinal vasoconstrictor regions are tonically active, continuously send sympathetic signal to smooth muscle → maintaining vascular tone (혈관의 안정 수축도) 2) Parasympathetic neural influence (부교감신경조절) - ACh induces vasorelaxation. But, parasympathetic nerve itself is not involved in the control of blood flow 3) Humoral factor (체액성인자) Epinephrine: secreted from adrenal medulla (부신수질) - acts on β1 receptor of the heart → ↑cardiac output, ↑heart rate - acts on β2 receptor of vessels, especially arteriolar smooth muscle → muscle relaxation → ↓PVR → ↑blood flow Angiotensin: potent vasoconstrictor Atrial natriuretic peptide (ANP): potent vasorelaxant Lymphatic System (림프계) Lymphatic System (림프계) 1. Functions of Lymphatic Vessels - returns body fluids and proteins filtered from capillaries to the circulatory system (right heart) - transports lipid and fat-soluble vitamins absorbed by GI tract into the blood - Lymph node (림프절): remove microbes and foreign substances by lymphocytes and phagocytes 2. Edema (부종) - abnormal accumulation of fluid in the interstitium - Causes 1) Lymphatic circulation disorder (림프순환장애) ex. injury, parasitic infection (filariasis), surgery 2) Congestive heart failure (울혈성 심부전): hydrostatic pressure of capillaries ↑ 3) Renal failure (신부전), Manutrition (영양실조): lack of plasma protein reduces oncotic pressure, resulting in increased filtration 4) Increase in the capillary permeability: inflammation Elephantiasis Lymphatic filariasis (림프사상충증) Blockage of lymph vessels