Lec. 2 Cardiovasular Physiology 2 (BIOL 171B) PDF

Preview

Summary

Download Lec. 2 Cardiovasular Physiology 2 (BIOL 171B) PDF

Description

Module 1: Electrical conduction in the heart Structure of the Heart

Contraction initiation: Autorhythmic Cells - Autorhythmic cells generate APs spontaneously - In addition to contractile cells, cardiac muscle contains autorhythmic cells that generate action potentials ‘on their own’ (without other inputs) - Critical for initiation and control of heartbeat cycle - Adjustable AP rates according to circumstances Pacemaker Potentials - Autorhythmic cells have unstable membrane potentials called pacemaker potentials. - “Funny” (If) , non-selective Na+ /K+ channels (𝐼 channels) contribute to pacemaker 𝑓

-

potential; ‘leaking’ Na+ & K+ Na+ enters faster than K+ leaves (Na+ driven by both electrical and concentration gradients), so membrane voltage slowly increases Pacemaker Potential: -60 mV (more polarized than contractile cells) Undergoes slow/spontaneous depolarization until it reaches threshold (done through “funny” channels) Whenever a pacemaker potential depolarized to threshold, the autorhythmic cell fires an action potential.

-

Pacemaker Potential - Na+ moving into the cell -> depolarizing the cell - K+ moving out of the cell -> hyperpolarized - Overall we see a slow depolarization (Na+ moving faster than K+)

Autorhythmic Action Potentials - As threshold is approached, Ca2+ channels open (-40 mV), 𝐼 channels start to 𝑓

-

close; when threshold is reached, many Ca2+ channels open - Depolarization Repolarization due to Ca2+ channels closing and K+ channels opening At about -60 mv, K+ channels close, 𝐼 channels open, and the cycle starts again 𝑓

-

Slow depolarization (due to funny channels) -> rapid depolarization -> rapid repolarization -> repeat of cycles

Comparison of Action Potentials in Cardiac and Skeletal Muscle

Autorhythmic Frequency is Modulated By Neurotransmitters - Sympathetic stimulation (catecholamines) increases frequency - Epinephrine (from adrenal medulla); Norepinephrine (from sympathetic neurons) - Bind and activate β1 adrenergic receptors → increase in cAMP in cells → prolonged opening of 𝐼 channels → faster depolarization (decreased the 𝑓

amount of time it takes to reach the threshold potential)

-

Increased AP Sympathetic stimulation and epinephrine depolarize the autorhythmic cell and speed up the pacemaker potential, increasing the heart rate.

Sympathetic Control of Heart Rate - Norepinephrine or Epinephrine will bind to the β1 adrenergic receptors -> activates the G-protein -> dissociate ɒ subunit -> subunit will bind to adenylate cyclase -> conversion of ATP to cAMP (secondary messenger) -> bind to protein kinase -> phosphorylate 2 channels -> 1st channel- phosphorylate the funny channel which will increase the Na+

conductance to depolarize the cell -> 2nd channel- T (transient) type calcium channel (increases the conductance of Ca2+ so that Ca+ enters the cell as well) -> Na+ & Ca2+ both enter the cell = faster depolarization -> increases firing of AP

Autorhythmic frequency is modulated by neurotransmitters - Parasympathetic input (acetylcholine) decreases frequency - Activates muscarinic cholinergic receptors that increase K+ permeability and decrease Ca2+ permeability - Cell hyperpolarizes, so pacemaker potential more negative; decreased Ca2+ permeability → decreased rate at which pacemaker potential depolarizes → lower frequency

-

Parasympathetic stimulation hyperpolarizes the membrane potential of the autorhythmic cell and slows depolarization, slowing down the heart rate.

Parasympathetic Control of Heart Rate - Acetylcholine binding to the Muscarinic cholinergic receptor (G-protein coupled receptor) -> Two Options -> 1) binding to T-type calcium channel, causing it to be inactivated (can no longer bring Ca2+ into the cell, depolarizes slower) -> 2) G-protein activates the K+ channel, K+ leaves the cell (hyperpolarizes cell) -> Both act to increase the amount of time that the autorhythmic cells spends in that pacemaker potential

-

Autorhythmic Cells: spontaneous due to funny channels

Autonomic Control of Heart Rate (Parasympathetic & Sympathetic Summary)

Left Side: Parasympathetic Right Side: Sympathetic

Contraction Cycle of The Whole Heart: Pacemakers and Electrical Conduction - Clusters of autorhythmic cells are organized into pacemakers that initiate heartbeat cycles: - Sinoatrial (SA) Node - Found at the vena cava (major sinus of the heart) and at the top of the atrium - Autorhythmic cells in the right atrium that serve as the main pacemaker of the heart - Atrioventricular (AV) Node - Found at the floor of the right atrium; at the interface between the atrium & the ventricle - Electrical signals from pacemakers are spread throughout the heart along specific conduction pathways -- bundles of Purkinje fibers -- to generate coordinated contraction for effective blood pumping

Pacemakers and Electrical Conduction - Depolarization current of AP in autorhythmic pacemaker cells spreads to contractile cells through gap junctions in the intercalated disks

-

Autorhythmic cells spontaneously fire action potentials. Depolarizations of the autorhythmic cells then spread rapidly to adjacent contractile cells through gap junctions.

Electrical Conduction Pathways in the Heart - The Sinoatrial (SA) Node): a cluster of autorhythmic cells in the right atrium - The main pacemaker - Internodal pathways (non-contractile) send depolarization to the atrioventricular node (AV) - Depolarization moves from AV node through Purkinje fibers in the AV bundle in the septum between the ventricles - AV bundle fibers divide into left and right branches - Electrical communication in the heart begins with an action potential in an autorhythmic cell. The depolarization spreads rapidly to adjacent cells through gap junctions in the intercalated disks - SA Node -> Internodal Pathways -> AV Node -> AV Bundle -> Bundle Branches -> Purkinje Fibers

Electrical Conduction During One Heartbeat

1.

2. 3. 4.

5.

Contractile cells are electrically connected through gap junctions and mechanically connected through desmosomes SA node depolarizes ○ The electrical signal for contraction begins when the SA node fires an action potential and the depolarization spreads to adjacent cells through gap junctions Depolarization spreads rapidly to AV node on internodal pathways ○ Electrical conduction is rapid through the internodal conduction pathways… Depolarization spreads more slowly across atria; conduction slows through AV node ○ … but slower through the contractile cells of the atria Depolarization spreads quickly to apex of heart through AV bundle fibers ○ The electrical signal passes from the AV node through the AV bundle and bundle branches to the apex of the heart Depolarization spreads upward from apex ○ The Purkinje fibers transmit impulses very rapidly, with speeds up to 4 m/sec, so that all contractile cells in the apex contract nearly simultaneously

Module 2 - Cardiac Cycle and The Control of Heart Function Contraction Cycle: Mechanical Events

-

Diastole: Time when cardiac muscle relaxes - Diastolic Pressure: low pressure in pulse Systole: Time when cardiac muscle contracts - Systolic Pressure: high pressure in pulse The chambers of the heart spend more time in diastole than in systole

Contraction Cycle 1. Late Diastole: Atria and ventricles relaxed; passive refilling (pressure gradient) - AV valves between the atria and ventricles open. 2. Atrial Systole: Atrial contraction pushes small volume of blood into ventricles - Blood flows from atria to ventricles - At the end of atrial systole the ventricles contain the largest volume they will hold during the cycle. This maximal volume is called the end-diastolic volume (EDV) 3. Ventricular Systole: Ventricles contract - Initially isovolumic: AV valves close; not enough pressure to open semilunar valves - S1: 1st heart sound, “lub” - Closing of AV valves 4. Ventricular Ejection: Now enough pressure to open semilunar valves; blood is ejected into aorta & pulmonary artery - the AV valves remain closed - The volume of blood left in the ventricle at the end of contraction is known as the end- systolic volume (ESV) . 5. Ventricular Relaxation: isovolumic, ventricular pressure falls, semilunar valves close; atria start to refill - 2nd heart sound, “dub” - Closing of Semilunar Valve - The AV valves remain closed because ventricular pressure, although falling, is still higher than atrial pressure. This period is called isovolumic ventricular relaxation because the volume of blood in the ventricles is not changing.

- Outside Circle: Ventricle - Purple: Contraction in Ventricle - Inside Circle: Atria - Orange: Contraction

Pressure-Volume Relationship in Left Ventricle For 1 Cardiac Cycle

-

-

-

-

-

EDV = End-Diastolic Volume ESV = End-Systolic Volume A → B: Bicuspid (mitral) valve opens, atrial bloods enters ventricle, volume increases, little pressure change - Volume ↑, Pressure = - Point B: EDV (maximal volume after ventricle is filled) B → C: Ventricular contraction begins, bicuspid valve closes, semilunar valve still closed, constant volume but increased pressure - Volume = , Pressure ↑ C → D: Semilunar valve opens, blood enters aorta, pressure mostly increases while volume decreases - Volume ↓ , Pressure ↑ - Stroke Volume: 70mL - Point D: ESV (volume of blood after it has been ejected) ~ 65 mL D → A: Ventricle relaxes, pressure decreases, semilunar valve closes when pressure in ventricle is less than atrium - Volume = , Pressure ↓ Notes: - Point A: Once pressure in the atrium exceeds pressure in the ventricle, the mitral valve (left AV valve) between the atrium and ventricle opens - Point A -> B: Atrial blood now flows into the ventricle, increasing its volume. The last portion of ventricular filling is completed by atrial contraction - Point B: The ventricle now contains the maximum volume of blood that it will hold during this cardiac cycle, the end-diastolic volume (EDV) - Point B -> C: When ventricular contraction begins, the mitral (AV) valve closes. With both the AV valve and the semilunar valve closed, blood in the ventricle has nowhere to go. Nevertheless, the ventricle continues to contract, causing the pressure in this chamber to increase rapidly during isovolumic contraction - Point C: Once ventricular pressure exceeds the pressure in the aorta, the aortic valve opens (left semilunar valve) - Point C -> D: Pressure continues to increase as the ventricle contracts further, but ventricular volume decreases as blood is pushed out into the aorta - Point D: The end-systolic volume (ESV) is the minimum volume of blood the ventricle contains during one cycle. - Point D -> A: Once pressure in the ventricle falls below aortic pressure, the semilunar valve closes, and the ventricle again becomes a sealed chamber. The remainder of relaxation occurs without a change in blood volume, and so this phase is called isovolumic relaxation.

Cardiac Output Adjustment - Cardiac Output = Amount of blood pumped per unit time - = Heart Rate X Stroke Volume (pump efficiency)

-

-

Stroke Volume = EDV - ESV - At Rest: ~ 135 mL - 65 mL = 70 mL Variation of Cardiac Output (CO) With Activity: - At Rest: HR = 56 bpm, SV = 70 mL - CO = 56 beats/min x 70 mL/beat = 3,920 mL/min (3.92 L/min) - During Marathon: HR = 120 bpm, SV = 100 mL - CO = 120 beats/min x 100 mL/beat = 12,000 mL/min (12 L/min) - In Very Intense Exercise: HR = 170, SV = 100 mL - CO = 170 beats/min x 100 mL/beat = 17,000 mL/min (17 L/min) Normal heart rate doesn’t go much higher than ~200 bpm even at maximum exercise intensity - Age Dependent; standard ‘formula’ is: maximal HR = 220 - Age - In Very Intense Exercise: HR = 180, SV = 100 mL - CO = 180 beats/min x 100 mL/beat = 18,000 mL/min (18 L/min)

Length-Tension Relationship: Frank-Starling Law of The Heart - Frank-Starling Law of The Heart: The stroke volume is proportional to the EDV

-

-

A consequence of the contractility of heart muscle -> the heart pumps all of the blood that returns to it - As additional blood enters the heart, the heart contracts more forcefully and ejects more blood - Stroke volume increases as end-diastolic volume increases (Force vs Stretch) Venous Return Also Regulates Stroke Volume, affected by: 1. Skeletal muscle pump (squeeze veins) 2. Respiratory pump 3. Vasoconstriction by sympathetic activity - End-diastolic volume is normally determined by venous return, the amount of blood that enters the heart from the venous circulation

Cardiac Output Control: Stroke Volume Regulation - Inotropic agents: Affect contractility and therefore stroke volume

-

Catecholamines - Epinephrine - Norepinephrine - Both ↑ contractility (Ventricular end-diastolic volume) -> ↑ stroke volume - Positive inotropic agents because they increase contractility: - Shorter Contractions - More Forceful Contractions - Sympathetic Inputs Only (Epinephrine/ Norepinephrine) - Parasympathetic system (acetylcholine) doesn’t affect stroke volume directly

Cardiac Output Control: Heart Rate Regulation - Sympathetic and Parasympathetic Branches are antagonistic for HR: - Sympathetic: ↑ HR - Parasympathetic: ↓ HR - HR is increased either by decreasing parasympathetic activity (usual) or increasing sympathetic activity (e.g., epinephrine or norepinephrine) - Block all autonomic input to the heart: SA node fires at intrinsic rate of ~ 90/min. - So, normal HR of 60-80 bpm requires parasympathetic input - Exercise: ↓ Parasympathetic & ↑ Sympathetic

-

Left: Parasympathetic Right: Sympathetic

Module 3: Heart Diagnostics and Pathologies Electrocardiograms and Events In The Cardiac Cycle

-

Electrocardiograms (ECGs): show the summed potentials generated by all heart cells (contractile, autorhythmic, etc.). Different ECG components relate to depolarization or repolarization of the atria and ventricles The ECG is used to relate electrical events with mechanical events of the heart.

Components of an ECG (aka EKG) - P wave: Depolarization of Atria - QRS complex: Progressive ventricular depolarization and atrial repolarization - T wave: Repolarization of Ventricles - Mechanical Events Lag Behind Electrical Events: - Atrial Contraction: Late P and into PR interval - Ventricular Contraction: After Q through T

-

Electrocardiograms and Events in The Cardiac Cycle

1) P Wave: SA node starts to fire; Atrial Depolarization a) Full depolarization occurs when that signal has gone from the SA node through AV nodes 2) PQ or PR: Conduction through AV node to AV bundle ; Ventricle is completely filled a) The electrical signal is slowing down as it passes through the AV node (AV node delay) and AV bundle. 3) Q Wave: Represents the movement of the electrical signal down through the bundle branches (septum of the heart) 4) R Wave: Moving to the Purkinje fibers back up through the heart 5) S Wave: Polarization moving fully up through the ventricle 6) ST: Atria fully repolarized; Ventricles fully depolarized a) Pressure in ventricle exceeds that of the atria -> AV valves shut (1st heart sound) 7) T Wave: Repolarization of the Ventricles -> relaxation

ECG is Different From Voltages in a Single Myocardial Cell

-

ECG shows summed electrical activity of all heart cells, recorded from body surface

-

AP from a single ventricular cell (recorded from an intracellular electrode)

-

Why They’re Different: - Summed Potentials in ECG give a more complex pattern - Resistance through body and skin yields much lower potentials in ECG (~110 mV for a single cell AP vs. ~1 mV from ECG)

Wiggers Diagram - ECG (Top) - Pressure in left ventricle, left atrium, and aorta (Middle): - Atrial Systole: - Beginning: Left Atrial greater pressure than Left Ventricle -> Blood flows from atrium to ventricle passively (AV Valves open) - End: Atria contracts -> final push of blood - Point C: Ventricular Pressure exceeds atrial pressure - Aorta pressure greater than ventricle = Semilunar Valves shut - Isovolumic Ventricular Contraction: - Point C -> A: Ventricular pressure exceeds atrial pressure -> causes mitral valve to shut -> hear first heart sound - Ventricular Systole: - Point A -> B : Semilunar valves open (ventricle pressure greater than aorta pressure) - Early Ventricular Systole:

-

Point B -> D: Pressure in ventricle lower than aorta pressure -> semilunar valve shuts -> 2nd heart sound - D: Mitral Valves Open - Late Ventricular Systole: Passive increase Left Ventricular Volume (Bottom): - Atrial Systole: - Passive filling into the ventricle - Isovolumic Ventricular Contraction: - Constant volume - Ventricular Systole: - Massive ejection of blood (↓ Volume) - Early Ventricular Systole: - Passive increase in volume (↑ volume) - Late Ventricular Systole: - Passive increase in volume (↑ volume) - Atrial Systole: - Mild push of blood due to contraction in atria (↑ volume)

-

Wiggers Diagram Summary -

Systole: The period of chamber contraction and blood ejection which corresponds to - The period between the QRS complex and the end of the T wave - The period between the closure of the mitral/tricuspid valves (AV) and the closure of the aortic/pulmonic valve (Semilunar Valves) Diastole: The period of chamber relaxation and cardiac filling which corresponds to - The period between the end of the T wave and the end of the PR interval - The period during which the mitral valve/tricuspid valves (AV) are open.

-

-

Events During Systole: -

-

-

Isovolumetric ventricular contraction - The beginning of this phase corresponds with the peak of the R wave - This corresponds to Phase 0 (rapid sodium influx) of the ventricular myocyte action potential - The ventricles begin to contract during this period - This contraction increases the ventricular chamber pressure and closes the mitral and tricuspid valves. - As a result, there is a fixed ventricular volume during this contraction Early ejection - The contracting ventricles achieve a pressure high enough to open the aortic and pulmonic valves, and rapidly empty into the systemic and pulmonary circulations. - This period corresponds to Phase 2 (plateau, rapid calcium influx) of the cardiac myocyte action potential - On the surface ECG, the end of this phase corresponds to the beginning of the T wave Late ejection - This period begins when ventricular pressure starts to drop, and ends with the closure of the aortic and pulmonic valves - The end of this period corresponds to the peak of the T wave on the surface ECG - This corresponds to Phase 3 (repolarisation) of the cardiac myocyte action potential

-

Events During Diastole: -

-

-

-

Isovolumetric relaxation - The ventricles relax without any change in volume - The pressure drops until the tricuspid and mitral valves open - This period corresponds to the end of the T wave on the surface ECG, and the end of Phase 3 of the action potential Early rapid diastolic filling - During this period the relaxing ventricles have pressure lower than atrial pressure, and they fill rapidly - 80% of the ventricular end-diastolic volume is achieved during this phase - Coronary blood flow is maximal during this phase Late slow diastolic filling - Ventricular and atrial pressures equilibrate and the atria act as passive conduits for ventricular filling - The end of this phase corresponds to the end of the P-wave on the surface ECG Atrial systole - The atria contract (right first, then le...