Cardiovascular Physiology Lecture Notes PDF

Cardiovascular Physiology Joe Sepe, PhD CV 2 October 9th, 2024 Session Learning Objectives: Recall the sequence of the conduction pathway in the healthy heart, beginning with the SA node. Compare and contrast the...

Cardiovascular Physiology Joe Sepe, PhD CV 2 October 9th, 2024 Session Learning Objectives: Recall the sequence of the conduction pathway in the healthy heart, beginning with the SA node. Compare and contrast the function and action potential waveforms (including ion channels responsible) of contractile cells, conducting cells, and nodal cells. Recall the phases (0-4) of cardiac cell action potentials. Describe excitation-contraction coupling in cardiac muscle cells, including the role of calcium and the receptors involved. Parallel vs Series Arrangement of Vascular Beds Pulmonary circuit is arranged in-series, systemic is in-parallel. Same quality of blood to all tissues Allows for better regulation of blood flow Takes less pressure than if arranged in series Guyton, Figure 14.1  Total resistance across a system arranged in parallel is less than if the same system was arranged in series. Costanzo, Figure 4.5  Know the path of blood Sequence of blood vessels in the systemic circulation: Arteries Arterioles Capillaries Venules Veins Costanzo, Figure 4.1  Electrical connections between cardiac muscle cells (coordination of the heart beat) “Adhesive” that holds the neighboring cells together Electrical synapse Connected via gap junctions = rapid communication! Functional syncytium (heart muscle cells are synchronized in health) Cardiac Myocytes Striated Mostly mononucleated (one nucleus) Branched ends Cardiac Muscle Compared to Skeletal and Smooth All three types: Sliding filaments and cross-bridges ATP powers the force generation Elevated Ca2+ triggers contraction Ways cardiac is similar to skeletal: Ways cardiac is similar to smooth: Has sarcomeres Pacemaker cells Striated Gap junctions (syncytium) Has troponin Ca2+ entry from ECF T-tubules Autonomic/hormones modulate activity Involuntary 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.  Timing of Activation of the Myocardium Rapid conduction through the atria allows the atria to contract at essentially the same time. AV Node delay gives the atria time to contract before ventricular excitation occurs. Rapid conduction through interventricular septum. Depolarization of the ventricular contractile cells is almost simultaneous. What does this excitation look at the Numbers (0-220) represent milliseconds from cellular level? start at SA node Costanzo, Figure 4.14  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 Not all cell types in the heart exhibit all the phases Costanzo, Figure 4.12 Nodal Cells Conducting Cells Cardiac Ion Channels Other ion channels exist in the heart, but these are the most important. Cell Type Pacemaker current T-type calcium Inward Na+ L-type calcium channel K+ (funny current; If) channel (“Transient”; (“Fast Na+; (“Long-lasting”; IT-Ca2+) IFast-Na+ ) Dihydropyridine Receptor; (IK+) IL-Ca2+) SA Node + + - + + AV Node + + - + + Conducting* + + + + + Atrial myocytes - - + + + Ventricular - - + + + myocytes Includes Bundle of His and Purkinje cell types (some sources consider the SA node and AV node as conducting cells, but here we’re focusing on the specialized conducting cells) ** the – indicates a negligible expression/amount of these channel types Opie, 4.1 Describing Excitation in the Heart Automaticity: Capable of generating spontaneous action potentials (pacemaker potential). SA node, AV node, conducting cells. Sinus Rhythm: Normal cardiac excitation sequence beginning at the SA node. Latent Pacemaker: Not actively driving the. Includes AV node and conducting cells (cells that have pacemaker potential). Ectopic Pacemaker: Abnormal, any site/group of cells driving heart rhythm that is NOT the SA node. Location Intrinsic Firing Rate (action potentials/minute) SA Node 100-110 AV Node 60-80 Conducting Cells 40 (Bundle of His) 15-20 (Purkinje Fibers) Typical resting heart rate is lower than 80-110. This means, at rest, the human heart is primary influence by the parasympathetic nervous system (“vagal tone”). 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 important, but contraction of cardiac muscle! Proper relaxation (diastole) is beyond this course’s scope essential for the ventricle to refill with blood. Costanzo, Figure 4.15