Cardiovascular Physiology PDF

Cardiovascular Physiology Joe Sepe, PhD CV 3 October 11th, 2024 Session Learning Objectives: Identify and list the sequence of events of excitation-contraction coupling in cardiac muscle, with specifical detail on the ro...

Cardiovascular Physiology Joe Sepe, PhD CV 3 October 11th, 2024 Session Learning Objectives: Identify and list the sequence of events of excitation-contraction coupling in cardiac muscle, with specifical detail on the role of calcium in regulating contraction List the 4 phases of the cardiac cycle Describe the events occurring during each phase of the cardiac cycle Compare and contrast systole and diastole Define stroke volume and its significance Conduction Pathway 1. SA node. This is the “true” pacemaker of the heart. In a healthy heart, these cells are the first to generate an action potential, beginning the electrical events of the cardiac cycle. 2. Atrial contractile cells. Atrial “kick”. 3. AV node. Propagation is slow (“delay”). 4. Bundle of His 5. Bundle branches Conducting cells 6. Purkinje Fibers Nodal cells and conducting cells can generate their own action potentials- meaning they’re all potential sources of arrhythmia (but also serve as a safety mechanism). Contractile cells cannot 7. Ventricular contractile cells. spontaneously generate their own action potentials.  The Action Potential of a Cardiac Ventricular Contractile Cell Phase 0: Depolarization. Fast Na + channels open. Phase 1: Initial Repolarization. Fast Na + channels close, transient (fast) K+ channels open) Phase 2: Plateau. L-type Ca 2+ channels open and transient K+ channels close. Phase 3: Rapid Repolarization. L-type Ca 2+ channels close and slow K+ channels open. Phase 4: Resting Membrane Potential. -80 to -90mV in ventricular contractile cells. (This phase is the pacemaker potential in some cell types) Guyton, Figure 9.5 Nodal Cells Conducting Cells Autonomic Nervous System Has a Tremendous Impact on the Function of the Heart More to come on this on Monday The Spread of Excitation What’s all the excitement about? Cardiac Muscle Excitation-Contraction Coupling Calcium-induced calcium release (CICR) Similar to what you saw in smooth muscle in terms of Ca2+ from the ECF entering the cell and causing additional Ca2+ release from the sarcoplasmic reticulum (SR) Bers, 2002. Nature. Step by Step 1) The membrane is depolarized by Na+ entry as an action 7) Ca2+-ATPase pumps return Ca2+ to the SR potential begins 8) Ca2+-ATPase pumps (and also Na+/Ca2+ 2) Depolarization opens L-type Ca2+ channels in the T- exchangers) remove Ca2+ from the cell into the tubules ECF 3) A small amount of “trigger” Ca2+ enters the cytosol, 9) Membrane is repolarized when K+ exits to contributing to cell depolarization. This trigger Ca2+ binds end the action potential to and opens ryanodine receptors (RyR) located in the SR membrane (calcium-induced calcium release) 4) Ca2+ flows out of the SR into the cytosol, raising the Ca2+ concentration (for every 1 Ca2+ that enters cell through L-type channel, 10 Ca2+ are released from SR through RyR) 5) Binding of Ca2+ to troponin exposes cross-bridge binding sites on thin filaments (actin). 6) Cross-bridge cycling causes force generation and sliding of thick and thin filaments. No new information, just the same concept represented by a figure from another source Guyton, Figure 9.7 Refractory Periods of Cardiac Muscle Absolute Refractory Period (ARP): The ventricular cell is completely refractory to fire another action potential, regardless of stimulus size. Fast-Na+ channels are inactive and unavailable to carry inward, positive current. Relative Refractory Period (RRP): Begins at the end of ARP and continues until the cell membrane has almost fully repolarized. Some amount of Fast-Na+ channels have recovered and are available to open (and carry inward current) again. A physiological safety mechanism. We do NOT want tetanic ERP and SNP are also important, but contraction of cardiac muscle! Proper relaxation (diastole) is beyond the scope of this course essential for the ventricle to refill with blood. Costanzo, Figure 4.15 The Cardiac Cycle: Mechanical part of our Biological pump (relaxation of the ventricles) Diastole Shorter; Longer; 1/3 of 2/3 of time time Systole (contraction of the ventricles) 4 Phases of the Cardiac Cycle *Always in reference to the left ventricle by default Ventricular filling diastole Isovolumetric contraction systole This is one cardiac Ejection systole cycle Isovolumetric relaxation diastole End product of each cardiac cycle: Strove Volume (SV), the volume of blood ejected from each ventricle per beat (mLs/beat). SV= End-Diastolic Volume – End-Systolic Volume SV = EDV - ESV Ventricular Filling (Diastole) The ventricles fill with blood during diastole. Initial period of ventricular filling is passive; blood passively moving from atria to ventricles. Followed by “atrial kick” (atria contract). This contributes an additional 10-20% of blood to the ventricles. The end of this phase is the end of diastole: “End Diastolic Volume” (EDV). EDV is the final volume of blood in the ventricle after filling. AV Valves Open ~135 mLs @rest Aortic and Pulmonary Valves Closed Isovolumetric Contraction (Systole) Ventricles contract (what electrical event on ECG corresponds to this mechanical event?) 1st heart sound at start of this phase (S1): “Lub”, caused by AV valves closing Volume constant at EDV Pressure in ventricles < pressure in aorta and pulmonary artery AV Valves Closed Pressure in ventricles > pressure in atria Aortic and Pulmonary Valves Closed Ejection (Systole) Pressure in ventricles > pressure in aorta and pulmonary artery Stroke volume: volume of blood ejected from each ventricle per beat (~70 mLs at rest) Reach “End Systolic Volume” (ESV): the volume of blood remaining in the ventricle after ejection. ESV = EDV - SV AV Valves Closed Is the SV the same from right and left ventricle? Aortic and Pulmonary Valves Open Isovolumetric Relaxation (Diastole) 2nd heart sound at start of this phase (S2): “Dup”, caused by semilunar valves closing. Volume constant at ESV Pressure in ventricles < pressure in aorta and pulmonary artery AV Valves Closed Pressure in ventricles > pressure in atria Aortic and Pulmonary Valves Closed Wiggers’ Diagram Pressures Volumes All in ECG one chart! Phases of cardiac cycle When pressure lines cross, important events occur (and valves open/close) “LUB” (AV valves close) and “DUP” (semilunar valves close) heart sounds are due to valves closing. Monday Office Hours (2-3pm): We’ll draw the Wiggers’ Diagram Ejection Fraction and Heart Failure Ejection fraction is a measure of the efficiency of the heart. It can be measured from either ventricle, but is typically measured in the LV. Average male value: 70 x 100 = 58.3% 120 Normal EF values: 55-70%. Values below this range could be indicative of heart failure. Heart failure with reduced ejection fraction (HFrEF): the “traditional” marker of heart failure (this is changing). Could be indicative of systolic dysfunction. Heart failure with preserved ejection fraction (HFpEF): the ventricle is stiff and has difficulty relaxing. Could be indicative of diastolic dysfunction. Cardiac Output and its Regulation Cardiac output (CO) is the volume of blood ejected from each ventricle per minute. It is the product of heart rate (HR) and stroke volume (SV), and is typically expressed in liters/min. CO = HR x SV Think back to the equation for flow (F). CO is Flow! It is a volume of blood per unit time “Average” values: 70 beats/min x 70 mL/beat = ~5 L/min Can be as high as 25-30 L/min during exercise! How can cardiac output be regulated? 1. Autonomic Innervation of the Heart (Adrenal medulla) *The majority (75-80%) of beta-adrenergic receptors in the heart are β1