Week 3 PSL Lecture Notes PDF

PSL301H – Lecture 4: Regulation of cardiac output How is cardiac output regulated? Silverthorn 7th ed: 468-472 Silverthorn 8th ed: 466-472 ESPVR and EDPVR Cardiac Performance in Ventricles ESV = end systolic volume (~65 ml) EDV = end diastolic volume (~135 ml) Stroke volume SV = EDV-ESV Amount of bl...

PSL301H – Lecture 4: Regulation of cardiac output How is cardiac output regulated? Silverthorn 7th ed: 468-472 Silverthorn 8th ed: 466-472 ESPVR and EDPVR Cardiac Performance in Ventricles ESV = end systolic volume (~65 ml) EDV = end diastolic volume (~135 ml) Stroke volume SV = EDV-ESV Amount of blood pumped by 1 ventricle in 1 contraction Cardiac output CO = HR x SV Amount of blood pumped per ventricle per unit time ~5L/min (~70 beats/min * 70 ml/beat=4.9L/min) Normal blood volume is ~ 5L Cardiac reserve difference between resting and maximal CO The CV System as a series of “bags” with different compliances Copyright © 2009 Pearson Education, Inc. Stroke Volume Frank-Starling law states stroke volume increases as EDV increases (“Starling curve” shown below) Length-force relationships in intact heart Starling curve Figure 14-28 How does an increased EDV lead to increased SV? Stretch increases # of crossbridges and approaches optimal sarcomere length Stroke Volume EDV is affected by venous return Venous return is affected by Skeletal muscle pump Respiratory pump Sympathetic innervation Check all that apply. What would happen to cardiac function if you Increased the pressure in the venous “bag”? A. increased SV B. increased EDV C. increased ESV D. increased CO E. increased HR Copyright © 2009 Pearson Education, Inc. “Extrinsic” Factors Influencing Stroke Volume Contractility is the increase in contractile strength independent of stretch independent of EDV Increase in contractility comes from: Increased sympathetic stimuli Certain hormones Ca2+ and some drugs Catecholamines Modulate Cardiac Contraction Epinephrine and norepinephrine bind to b1-receptors that activate cAMP second messenger system resulting in phosphorylation of Voltage-gated Ca2+ channels Phospholamban Open time increases Ca2+-ATPase on SR Ca2+ entry from ECF KEY Ca2+ stores in SR Ca2+ released Ca2+ removed from cytosol faster Shortens Ca-troponin binding time SR = Sarcoplasmic reticulum ECF = Extracelllular fluid More forceful contraction Shorter duration of contraction Inotropic Effect The effect of norepinepherine on contractility of the heart Altering the Inotropic State of the Heart Changes the Slope of the ESPVR Autonomic Nervous System: Extrinsic Regulation Heart Rate KEY Integrating center Cardiovascular control center in medulla oblongata Efferent path Effector Tissue response Sympathetic neurons (NE) Parasympathetic neurons (Ach) b1-receptors of autorhythmic cells Muscarinic receptors of autorhythmic cells Na+ and Ca2+ influx K+ efflux; Ca2+ influx Rate of depolarization Hyperpolarizes cell and rate of depolarization Heart rate Heart rate Summary Slide: Stroke Volume and Heart Rate Determine Cardiac Output CARDIAC OUTPUT CO = HR x SV is a function of Heart rate Stroke volume determined by determined by Rate of depolarization in autorhythmic cells Force of contraction in ventricular myocardium Decreases Increases Due to parasympathetic innervation b1R, Gas, NE/epinephrine, Increased cAMP/PKA more I(f) increases Sympathetic innervation and epinephrine increases M2R , Gai, ACh, lowered cAMP/PKA, less I(f) is influenced by Contractility b1R, Gas, NE/epinephrine Increased cAMP/PKA VGCC, SERCA = SR Ca2+ Venous constriction End-diastolic volume which varies with Venous return aided by Skeletal muscle pump Respiratory pump PSL301H – Lecture 3: The cardiac cycle How do electrical signals initiate contraction and cause blood movement? What is the cardiac cycle? Silverthorn 7th ed: 461-466 Silverthorn 8th ed: 459-464 Cardiac action potential to Aortic Flow: Summary 1. Electrical signals originate in the SA node, and propagate through the heart. Can be regulated. 2. electrical signals are converted by contractile cells to generate force and pump blood. 3. requires ordered electrical and contractile mechanism 4. We can monitor these signals and sounds to accurately assess cardiac function. 5. Systems need to work at near 100% effectiveness What is the cardiac cycle? Sequence of events that occur when the heart beats. There are two phases of this cycle: 1. Diastole - Ventricles are relaxed. 2. Systole - Ventricles contract. Overall Aim: Understand and integrate electrical activity, contraction, and blood flow in/out of the heart Cardiac cycle 3 General Principles: 1) The heart is a biological pump ! Contraction-relaxation cycle generates pressure gradients ! Directs the orderly movement of blood through the circulation. 2) Blood flows high pressure ! low pressure 3) Events on the right and left sides of the heart are the same, but pressures are lower on the right. Mechanical events of the cardiac cycle START 5 1 Late diastole—both sets of chambers are relaxed and ventricles fill passively. Isovolumic ventricular relaxation—as ventricles relax, pressure in ventricles falls, blood flows back into cusps of semilunar valves and snaps them closed. 2 Atrial systole—atrial contraction forces a small amount of additional blood into ventricles. S1 S2 4 Ventricular ejection— as ventricular pressure rises and exceeds pressure in the arteries, the semilunar valves open and blood is ejected. 3 Isovolumic ventricular contraction—first phase of ventricular contraction pushes AV valves closed but does not create enough pressure to open semilunar valves. Pressures in aorta, ventricle, atrium Time (msec) 0 100 200 300 400 500 600 700 800 120 B 90 Aorta Dicrotic notch A Pressure (mm Hg) 60 Left venticular pressure 30 Left atrial pressure 0 D C S1 Heart sounds Atrial systole Atrial systole S2 Ventricular systole Isovolumic ventricular contraction Ventricular systole Ventricular diastole Early ventricular diastole Late ventricular diastole Atrial systole Atrial systole Ventricular pressure and volume Time (msec) 0 100 200 300 400 500 600 700 800 120 90 Pressure (mm Hg) 60 Left venticular pressure 30 0 135 S2 S1 E Left ventricular volume (mL) F 65 Atrial systole Atrial systole Ventricular systole Isovolumic ventricular contraction Ventricular systole Ventricular diastole Early ventricular diastole Late ventricular diastole Atrial systole Atrial systole Ventricular pressure and volume Time (msec) 0 100 200 300 400 500 600 700 800 120 90 Pressure (mm Hg) 60 Left venticular pressure 30 0 135 S2 S1 E Left ventricular volume (mL) F 65 Atrial systole Atrial systole Ventricular systole Isovolumic ventricular contraction Ventricular systole Ventricular diastole Early ventricular diastole Late ventricular diastole Atrial systole Atrial systole Wiggers Diagram: overview Time (msec) 0 100 200 300 400 500 600 700 800 QRS complex Electrocardiogram (ECG) QRS complex P T P 120 90 Pressure (mm Hg) B Aorta 60 Left venticular pressure 30 Left atrial pressure 0 C Heart sounds 135 For the Wigger’s diagram shown at left, match the letters in boxes with the following events of the cardiac cycle: Dicrotic notch A 1. End-diastolic Volume 2. Aortic valve opens 3. Mitral valve opens 4. Aortic valve closes 5. Mitral valve closes 6. End-systolic volume D S1 S2 E Left ventricular volume (mL) 65 Atrial systole F Atrial systole Ventricular systole Isovolumic ventricular contraction Ventricular diastole Ventricular Early Late systole ventricular ventricular diastole diastole Atrial systole Atrial systole Heart Sounds First heart sound Vibrations following closure of the AV valves “Lub” Second heart sound Vibrations created by closing of semilunar valve “Dup” Auscultation is listening to the heart through the chest wall through a stethoscope What are some further applications of this knowledge? What ways are there to diagnose this?? Pressure Volume Loop: Ventricular filling Left ventricular pressure (mm Hg) 120 KEY EDV = End-diastoilc volume ESV = End-systolic volume 80 40 START A 0 65 100 Left ventricular volume (mL) A¢ 135 Pressure Volume Loop: End Diastolic Volume Left ventricular pressure (mm Hg) 120 KEY EDV = End-diastoilc volume ESV = End-systolic volume 80 40 START A 0 65 100 Left ventricular volume (mL) A¢ B 135 EDV Pressure Volume Loop: Isovolumetric Contraction Left ventricular pressure (mm Hg) 120 KEY EDV = End-diastoilc volume ESV = End-systolic volume 80 C 40 START A 0 65 100 Left ventricular volume (mL) A¢ B 135 EDV Pressure Volume Loop: Blood Ejection Phase Stroke volume Left ventricular pressure (mm Hg) 120 ESV D KEY EDV = End-diastoilc volume ESV = End-systolic volume 80 C 40 START A 0 65 100 Left ventricular volume (mL) A¢ B 135 EDV Pressure Volume Loop: Isovolumetric Relaxation Stroke volume Left ventricular pressure (mm Hg) 120 ESV D KEY EDV = End-diastoilc volume ESV = End-systolic volume 80 C 40 START A 0 65 100 Left ventricular volume (mL) A¢ B 135 EDV What information can PV Loops provide? 1) Stroke Volume 2) Atrial Filling Pressure (preload) 3) Aortic Pressure (afterload) PSL301H – Lecture 2: Cardiac excitability: heart rate and ECG What is the underlying reason that heart cells contract? What is the cause, the effect, and ways to use that information to study the heart? Silverthorn 7th ed: 453-461 Silverthorn 8th ed: 450-459 Two types of Cardiac action potentials Type 1: Non-pacemaker cell (myocyte) action potentials "fast response" action potentials - rapid depolarization in response to AP contractile cells are “soldiers” – need instructions to fire Make up most of the atrial and ventricular muscle wall Two types of Cardiac action potentials Type 2: Pacemaker (autorhythmic) cells Unstable resting potential- causes spontaneous firing Non-contractile cells- “generals”- provide firing instructions to muscular soldiers found in the sinoatrial and atrioventricular nodes Action Potentials in cardiac autorhythmic cells Funny current channels (If) cause unstable resting potential - permeable to both K+ and Na+ 20 Ca2+ channels close, K+ channels open Membrane potential (mV) 0 Ca2+ in K+ out –20 –40 Lots of Ca2+ channels open Threshold Ca2+ in –60 Pacemaker potential Action potential Time The pacemaker potential gradually becomes less negative until it reaches threshold, triggering an action potential. Net Na+ in Time Ion movements during an action and pacemaker potential If; Na influx>K efflux Some Ca2+ channels open, If channels If channels close If channels open open K+ channels close Time State of various ion channels Cardiac action potentials (roles for Na+ and Ca2+) Role of Na+ Cardiac muscle (non-pacemaker) cells Rapid depolarization phase caused by an opening of Na+ channels Cardiac pacemaker cells Slowly depolarizing pacemaker potential (If opening results in net Na+ influx) for autorhythmic cells Role of Ca2+ Cardiac muscle (non-pacemaker) cells Ca2+ influx prolongs the duration of the action potential and produces a characteristic plateau phase. Cardiac pacemaker cells Ca2+ ions are involved in the initial depolarization phase of the action potential. Electrical Conduction to Myocardial Cells How do autorhythmic signals reach muscle cells? Membrane potential of autorhythmic cel Membrane potential of contractile cell Cells of SA node Contractile cell Intercalated disk with gap junctions Depolarizations of autorhythmic cells rapidly spread to adjacent contractile cells through gap junctions. All cells of the intrinsic conduction system (wiring) have the ability to generate spontaneous action potentials - i.e. they are autorhythmic Copyright © 2009 Pearson Education, Inc. Copyright © 2009 Pearson Education, Inc. Electrical Conduction in the Heart Audiovisual https://www.youtube.com/watch?v=bxKBQqe_Bo0 Electrical Conduction in the Heart 1 1 SA node depolarizes. SA node AV node 2 Electrical activity goes rapidly to AV node via internodal pathways. 2 3 Depolarization spreads more slowly across atria. Conduction slows through AV node. THE CONDUCTING SYSTEM OF THE HEART SA node 3 Internodal pathways 4 Depolarization moves rapidly through ventricular conducting system to the apex of the heart. 5 AV node AV bundle 4 Bundle branches Purkinje fibers 5 Depolarization wave spreads upward from the apex. Nodes (Control Points) SA node Sets the pace of the heartbeat at ~70 bpm AV node (50 bpm) and Purkinje fibers (25-40 bpm) can act as pacemakers under some conditions….slower pacemaker activity AV node Routes the direction of electrical signals Delays the transmission of action potentials Conductive fibres are often sheathed (separated from myocyte connections) except for in specialized contact regions of atria and ventricles. Note also how atrial and ventricular myocyte syncytia are separated? By an inert fibrous tissue barrier - there are no GAP junctions between them. Why do you think this might be? Copyright © 2009 Pearson Education, Inc. Heart Rate is Controlled by both Symapthetic and Parasympathetic Nerves Copyright © 2009 Pearson Education, Inc. Heart rate regulation - SA node action potential firing rate is regulated by both and fibres Epi Copyright © 2009 Pearson Education, Inc. NE Ach Parasympathetic Control of Heart Rate Parasympathetic activity lowers heart rate: activates the vagus nerve that innervates the SA node. releases the neurotransmitter acetylcholine (Ach) that binds to muscarinic receptors (M2R) in SA node cells at rest, there is significant vagal tone on the SA node ! resting heart rate is between 60 and 80 beats/min. atropine, a muscarinic receptor antagonist, leads to a 20-40 beats/min increase in heart rate. Ach Copyright © 2009 Pearson Education, Inc. Control of Heart Rate To increase heart rate (above the intrinsic rate) Need activation of sympathetic nerves innervating the SA node that release the neurotransmitter norepinephrine (NE) that binds to betaadrenergic receptors (bARs) on SA node cells. Can also be stimulated by circulating catecholamines released from the adrenal gland during a sympathetic response Epi NE Sympathetic activity in SA node results in increased cAMP, increased PKA activity and increased Cav (L-type Ca2+ channels) and HCN (funny current) channel activity Copyright © 2009 Pearson Education, Inc. Membrane potential (mV) Membrane potential (mV) Modulation of Heart Rate by the Autonomic Nervous System Sympathetic stimulation Normal 20 0 –20 –40 –60 Depolarized More rapid depolarization 0.8 1.6 Time (sec) 2.4 20 Normal Parasympathetic stimulation 0 –60 Hyperpolarized Slower depolarization 0.8 1.6 Time (sec) 2.4 Review question Which of the following statements regarding autorhythmic cells is true? a) The depolarization phase requires the movement of K+ out the cell b) They are located on the outside of the heart c) The membrane potential is unstable, drifting between -90mV and – 55 mV d) Increasing the cellular concentration of cAMP will increase their rate of depolarization Control of Heart Rate vs Contraction strength Vagus nerves (Parasympathetic) causes a decrease in the SA node rate (thereby decreasing the heart rate). Parasympathetic fibers cannot change the force of contraction, however, because they only innervate the SA node and AV node. Sympathetic fibers increase SA node rates (thereby increasing the heart rate) and can increase the force of contraction because in addition to innervating the SA and AV nodes, they innervate the atria and ventricles themselves. Can we use what we learned of the heart anatomy and basic electrical properties to gain even more insight into health and disease??? Copyright © 2009 Pearson Education, Inc. The Electrocardiogram Three major waves: P wave, QRS complex, and T wave The electrocardiogram (ECG) is the oldest and the most commonly used cardiology procedure. It is noninvasive, simple to record and its cost is minimal. Electrical Activity - Overview Correlation between an ECG and electrical events in the heart Copyright © 2009 Pearson Education, Inc. Figure 14-21 (2 of 9) Copyright © 2009 Pearson Education, Inc. Figure 14-21 (3 of 9) Copyright © 2009 Pearson Education, Inc. 14-21CorrelateECGHeart_3_L Figure 14-21 (4 of 9) Copyright © 2009 Pearson Education, Inc. Figure 14-21 (5 of 9) Copyright © 2009 Pearson Education, Inc. Figure 14-21 (6 of 9) Copyright © 2009 Pearson Education, Inc. Figure 14-21 (7 of 9) Copyright © 2009 Pearson Education, Inc. Figure 14-21 (8 of 9) Comparison of ECG and myocardial action potential 1 mV 1 sec (a) The electrocardiogram represents the summed electrical activity of all cells recorded from the surface of the body. 110 mV 1 sec (b) The ventricular action potential is recorded from a single cell using an intracellular electrode. Notice that the voltage change is much greater when recorded intracellularly. Tips for analysis of an ECG QUESTIONS TO ASK WHEN ANALYZING ECG TRACINGS: 1. What is the rate: Is it within the normal range of 60–100 beats per minute? 2. Is the rhythm regular? 3. Are all normal waves present in recognizable form? 4. Is there one QRS complex for each P wave? If yes, is the P-R segment constant in length? If there is not one QRS complex for each P wave, count the heart rate using the P waves then count it according to the R waves. Are the rates the same? Which wave would agree with the pulse felt at the wrist? ECG: Normal and abnormal electrocardiograms Normal P, wide QRS Complete Block: alternate pacemaker in ventricle..Purkinje Fibers. Infarcted? ‘no P’, irregular QRS ‘no P’, no QRS Ventricular fibrillation Normal P, normal QRS P Not triggering QRS…… Problems where?? Second degree heart block: AV node