PAR3615 Paramedicine Medical Physiology II W2025 Lecture 3 PDF

PAR3615 Paramedicine – Medical Physiology II W2025 Lecture 3 Coronary perfusion and cardiac action potentials  Copyright / Intellectual Property Notice Materials posted to courses are subject to Intellectual Property and Copyright protection, and as such can...

PAR3615 Paramedicine – Medical Physiology II W2025 Lecture 3 Coronary perfusion and cardiac action potentials  Copyright / Intellectual Property Notice Materials posted to courses are subject to Intellectual Property and Copyright protection, and as such cannot be used and posted for public dissemination without prior permission from the College. For clarity, these protections are automatic once a work is created, and applies whether or not a copyright statement appears on the material. Students are bound by College policies, including AA 34 - Copyright, and SA 07 - Student Code of Conduct, and any student found to be using or posting course materials for public dissemination without permission is in breach of these policies and may be sanctioned.  Need HELP?? If you need help: 1. Email me for an appointment – can meet individually or as a group 2. Chat with me after or before class Email responses follow the AC policy – 48h grace (not including weekends and holidays) Expect email responses from me during regular College business hours with some exceptions. Ø After the 48h, please send me a polite reminder. J Dr. Pasan Fernando 3  Orientation of the heart Cardiac cell types Dr. Pasan Fernando  Describe the orientation of the heart Dr. Pasan Fernando Physio-pedia.com 5  Types of cells found within the heart Identify and describe the types of cells found within the heart. Dr. Pasan Fernando 6  The Pensive Paramedic Why do we have a tricuspid and a bicuspid valve? Dr. Pasan Fernando 7  Dr. Pasan Fernando 8  Dr. Pasan Fernando 9  Pressures within the heart chambers Dr. Pasan Fernando 10  Coronary Circulation - Arteries Aorta Pulmonary Superior trunk § Both left and right coronary arteries arise vena cava from base of aorta and supply arterial Left atrium blood to heart Anastomosis (junction of § Both encircle heart in coronary sulcus vessels) Left coronary § Branching of coronary arteries varies Right artery among individuals atrium Circumflex § Arteries contain many anastomoses artery Right (junctions) an-ass-toe-moe-sees coronary artery Left Ø Provide additional routes for blood ventricle delivery Right ventricle Anterior Ø Cannot compensate for coronary artery Right interventricular Dr. Pasan Fernando occlusion marginal artery § Heart receives 1/20th of body’s blood artery Posterior supply interventricular artery 11  Coronary Arteries and Intramural Vessels Intramural vessels within the myocardium Dr. Pasan Fernando Spaan et al., (2008). Phil. Trans. R. Soc. 12  Coronary Arteries - RCA Right coronary artery § Supplies right atrium, parts of both ventricles, and parts of cardiac (electrical) conducting system § Follows coronary sulcus (groove between atria and ventricles) § Main branches: Ø Marginal arteries—supply right ventricle Ø Posterior interventricular (posterior descending) artery— runs in posterior interventricular sulcus; supplies interventricular Dr. Pasan Fernando septum and adjacent parts of ventricles 13  Coronary Arteries - LCA Left coronary artery § Supplies left ventricle, left atrium, interventricular septum § Main Branches: Ø Anterior interventricular artery (left anterior descending artery)—follows anterior interventricular sulcus; supplies interventricular septum and adjacent parts of ventricles Ø Circumflex artery—follows coronary sulcus to the left; meets branches of right coronary artery posteriorly; marginal Dr. Pasan Fernando artery off of circumflex supplies posterior of left ventricle 14  Areas of the Heart Supplied By the LCA and RCA Area LCA RCA Atrium Left atrium Right atrium Right ventricle Part of the right Most of the right ventricle ventricle Left ventricle Most of the left Part of the left ventricle ventricle IVS Anterior 2/3 and AV Posterior 1/3 bundle SA node 40% of individuals 60% of individuals Dr. Pasan Fernando AV node 20% of cases 80% of cases 15  Describe how an organ/tissue is perfused What features allow perfusion into a tissue? Dr. Pasan Fernando 16  Aorta Pulmonary trunk As ventricles contract and intraventricular pressure rises, blood is pushed up against semilunar valves, forcing them open. Dr. Pasan Fernando Semilunar valves open 17  Cardiac Muscle Cells – Intercalated Discs Intercalated discs are connecting junctions between cardiac cells that contain: § Desmosomes: hold cells together; prevent cells from separating during contraction § Gap junctions: allow ions to pass from cell to cell; electrically couple adjacent cells Ø Allows heart to be a functional syncytium, a single coordinated unit Cardiac Intercalated Gap junctions (electrically Desmosomes (keep muscle cell Nucleus discs connect myocytes) myocytes from pulling apart) Dr. Pasan Fernando 18  Cardiac Muscle Cell Cardiac muscle cell Mitochondrion Nucleus Intercalated disc Mitochondrion T tubule Sarcoplasmic Z disc reticulum Nucleus Dr. Pasan Fernando Sarcolemma I band A band I band 19  Cardiac Muscle vs Skeletal Muscle Dr. Pasan Fernando 20  Cardiomyocyte - EC Coupling In cardiomyocytes: § Strength of cardiac muscle contraction depends on the quantity if Ca2+ in the ECF § The SR does not store enough Ca2+ for efficient contraction § Most of the ECF Ca2+ surrounding cardiomyoctes are localized to the T-tubules, i.e., within the ECF § The action potential opens VG-Ca2+ channels § Ca2+ enters sarcoplasm and stimulates the opening of SR – ryanodine receptors § The action potential also spreads down the T-tubules and stimulates the opening of the SR - ryanodine Dr. Pasan Fernando receptor. § Ca2+ binds troponin and EC coupling occurs 21  Cardiac Muscle vs Skeletal Muscle § Tetanic contractions cannot occur in cardiac muscles Ø Cardiac muscle fibers have longer absolute refractory period than skeletal muscle fibers – Absolute refractory period is almost as long as contraction itself – Prevents tetanic contractions – Allows heart to relax and fill as needed to be an efficient pump Dr. Pasan Fernando 22  Cardiac Muscle vs Skeletal Muscle § The heart relies almost exclusively on aerobic respiration Ø Cardiac muscle has more mitochondria than skeletal muscle so has greater dependence on oxygen – Cannot function without oxygen Ø Skeletal muscle can go through fermentation when oxygen not present Ø Both types of tissues can use other fuel sources – Cardiac is more adaptable to other fuels, including lactic acid, but must have oxygen Dr. Pasan Fernando 23  The Heart is Metabolically Flexible Dr. Pasan Fernando 24  Dr. Pasan Fernando 25  How do cardiomyocytes contract? What starts the contraction? What spreads the contractions through the entire heart? What moderates/modifies the contraction? Dr. Pasan Fernando 26  Setting the Basic Rhythm – Intrinsic conduction system Coordinated heartbeat is a function of: 1. Presence of gap junctions 2. Intrinsic cardiac conduction system Ø Network of noncontractile (autorhythmic) cells Ø Initiate and distribute impulses to coordinate depolarization and contraction of heart Dr. Pasan Fernando 27  Spread of Action Potentials Action potentials § Are initiated locally § Conducted over the surface of individual cells § Spread through direct contact with neighbouring cells § Spreading current passively depolarizes adjacent cell membrane to their thresholds à initiating an action potential at a new site Dr. Pasan Fernando 28  Cell-Cell Conduction of Cardiac APs Describe how action potentials spread between cardiomyocytes Dr. Pasan Fernando 29  Speed of AP Propagation in Cardiac Tissue Speed of AP propagation § Termed conduction velocity § Highly variable between different regions of the heart § Determined by: A. Cardiomyocyte (muscle cell) diameter B. Intensity of local currents C. Resistance properties of cell membranes and associated structures Dr. Pasan Fernando 30  Dr. Pasan Fernando 31  Dr. Pasan Fernando 32  More connective tissue in the SA node of older hearts Dr. Pasan Fernando Kharche SR, Vigmond E, Efimov IR, Dobrzynski H (2017) Computational assessment of the functional role of sinoatrial node exit pathways in the human heart. PLOS ONE 12(9): e0183727. https://doi.org/10.1371/journal.pone.0183727 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183727  Older hearts have slower SA node conduction velocities Dr. Pasan Fernando https://pubmed.ncbi.nlm.nih.gov/27598221/  Intrinsic Conduction System – The AV node 3. Atrioventricular (AV) node § In the inferior interatrial septal wall § Delays impulses approximately 0.1 second Ø Since fibers are smaller in diameter, they have fewer gap junctions Ø Allows complete atrial contraction prior to ventricular contraction Dr. Pasan Fernando § Inherent rate of 50´/minute in absence of SA node input 35  Intrinsic Conduction System – The AV node and Bundle Branches 4. Atrioventricular (AV) bundle (bundle of His) § In superior interventricular septum § Is the only electrical connection between atria and ventricles Ø Atria and ventricles are not connected via gap junctions 5. Right and left bundle branches § Two pathways in interventricular septum § Carry impulses toward apex of heart Dr. Pasan Fernando 36  Intrinsic Conduction System – Purkinje fibers 5. Subendocardial conducting network (Purkinje fibers) § Complete the pathway through interventricular septum into apex and ventricular walls § More elaborate on left side of heart § AV bundle and subendocardial conducting network depolarize 30´/minute in absence of AV node input § Ventricular contraction immediately follows from apex toward atria § Process from initiation at SA node to complete contraction takes ~0.22 seconds Dr. Pasan Fernando 37  Intrinsic Conduction System Superior vena cava Right atrium Pacemaker potential 1 The sinoatrial (SA) node (pacemaker) SA node generates impulses. Internodal pathway 2 The impulses Left atrium pause (0.1 s) at the atrioventricular Atrial muscle (AV) node. 3 The Subendocardial atrioventricular conducting (AV) bundle network AV node connects the atria (Purkinje fibers) to the ventricles. Ventricular 4 The bundle branches Pacemaker muscle conduct the impulses Inter- Plateau through the ventricular potential interventricular septum. septum 5 The subendocardial conducting network Dr. Pasan Fernando depolarizes the contractile 0 200 400 600 cells of both ventricles. Milliseconds Anatomy of the intrinsic conduction system showing the sequence Comparison of action potential shape of electrical excitation at various locations 38  Conducting System – Coordinated units Autorhythmic cells Location Firing Rate at Rest SA node 70–80 AP/min Aorta AV node 40–60 AP/min Bundle of His 20–40 AP/min Superior Interatrial pathway vena cava Sinoatrial (SA) node (pacemaker) Purkinje fibers 20–40 AP/min Internodal pathway Left atrium § Cardiac cells are linked by gap junctions Right atrium Left ventricle § Fastest depolarizing cells control Right ventricle other cells § SA node and AV node can fire Dr. Pasan Fernando spontaneous AP's….but….. § Fastest cells = pacemaker = set rate for rest of heart  Different Cardiac Cells Have Different Action Potentials Pacemaker cells § In SA node § Have unstable resting potentials § AV, BoH, BB, and PF all have spontaneous depolarization – see Purkinje fiber voltage at baseline Contractile cells § Atrial myocytes Ø Have sharp depolarization similar to ventricular myocytes Ø Have relatively short repolarization phase compared to ventricular Dr. Pasan Fernando myocyte § Ventricular myocytes (not shown) Ø have prolonged repolarization phase 40  Dr. Pasan Fernando 41  Action Potentials of Contractile Cardiac Muscle Cells 1 Contractile muscle fibers make up Action potential thr bulk of heart and are responsible for 20 Plateau Ap ma pumping action me Membrane potential (mV) en § Different from skeletal muscle contraction; 0 Tension cardiac muscle action potentials have development plateau (contraction) Tension (g) -20 Step 1 1 -40 § Depolarization opens fast voltage-gated Na+ channels; Na+ enters cell -60 § Positive feedback influx of Na+ causes Absolute rising phase of AP (from -90 mV to +30 refractory -80 period mV) Dr. Pasan Fernando 0 150 300 Time (ms) 42  Action 1 D potential throu Step 2 20 Plateau A pos many § Depolarization by Na+ also opens slow mem Membrane potential (mV) 2 ends Ca2+ channels 0 Tension § At +30 mV, Na+ channels close, but slow development (contraction) 2 P Tension (g) Ca2+ channels remain open, prolonging -20 throu depolarization 1 the c -40 chan – Seen as a plateau -60 Absolute refractory -80 period Dr. Pasan Fernando 0 150 300 Time (ms) 43  Action 1 D potential throu Step 3 20 Plateau A pos many memb § After about 200 ms, slow Ca2+ channels are Membrane potential (mV) 2 ends 0 closed, and voltage-gated K+ channels are Tension development open (contraction) 2 Pl Tension (g) -20 § Rapid efflux of K+ repolarizes cell to RMP throu the ce 1 3 § Ca2+ is pumped back into SR and out of cell -40 chann into extracellular space -60 Absolute 3 R refractory chan -80 period open bring its re Dr. Pasan Fernando 0 150 300 Time (ms) 44  Contractile Cardiac vs Contractile Skeletal Muscle § AP in skeletal muscle lasts 1–2 ms § in cardiac muscle it lasts 200 ms § Contraction in skeletal muscle lasts 15–100 ms § in cardiac contraction lasts over 200 ms Benefit of longer AP and contraction: § Sustained contraction ensures efficient ejection of blood § Longer refractory period prevents tetanic contractions Dr. Pasan Fernando 45  Cardiomyocyte – Action Potential vs. Force Generated Dr. Pasan Fernando 46  Skeletal Muscle – Can develop tension in different ways Skeletal muscle § Can receive multiple stimuli over a shorter period (frequency of stimulation) § Faster frequency develops more tension over time Dr. Pasan Fernando 47  Cardiac Muscle – Develops tension in only one way Cardiac muscle Only one possible way to generate tension – with a single stimulus Dr. Pasan Fernando 48  Absolute and Relative Refractory Periods § An area of cardiac muscle that has been excited cannot be re- excited until the myofibers are in relative refractory § Normal refractory periods is 0.25-0.3 seconds § Relative refractory is an additional ~ 0.05 seconds § Atrial muscle has a much shorter refractory period (0.15 seconds) Dr. Pasan Fernando 49  Phases of the Cardiac Action Potential Cardiac AP has five phases – accepted naming convention § AP from an adjacent myocyte triggers the AP in the receiving myocyte § Membrane potential reaches threshold (-60 to -65 mV), membrane conductance increases sharply as Na+ channels open Phase 0 » Na+ rushes inward; cell depolarizes and potential flips to +20 to +30 mV; called the overshoot (phase 0) Phase 1 » Membrane begins to repolarize but is short lived Phase 2 » Membrane potential stabilizes for 200-400 ms (plateau) Phase 3 » Membrane repolarizes Dr. Pasan Fernando Phase 4 » Membrane returns to resting potential 50  Inward and Outward Ionic Currents In cardiovascular physiology, the names of ion channels are associated with the direction of the ion flow (next slide) Things to consider: § Ions that influence the resting potential § The activity of the Na+/K+ ATPase channel – is it still on?? § Total time for ions to move and cause a change in the membrane potential and to re-establish themselves afterward Dr. Pasan Fernando 51  Myocardial Action Potential – Sequence of Permeability to Na+, Ca2+, and K+ Phase 0 § Fast sodium channels cause rapid depolarization; (iNa) is first inward current Phase 1 § Rapid but incomplete repolarization is caused by transient outward current (ito) Phase 2 § Small but long lasting inward current of Ca2+ (iCa-L) causes early plateau § Calcium comes in via L-type Ca2+ channels; abundant in T-tubules § Plateau is maintained by NCX, allows more Na+ to flow into cell Phase 3 § K+ channels gradually opens, allows outward current of potassium via delayed Dr. Pasan Fernando rectifier channels (ikv) Phase 4 § Phase 4 Na+ and Ca2+ channels closed, K+ rectifier channel keeps membrane at - 52 90 mV  Cardiomyocyte - Relaxation End of plateau phase § Ca2+ entry into sarcoplasm stops § Ca2+ is rapidly pumped back into the SR and out to the ECF (around the TT ECF) § Ca2+ is both pumped out via Ca2+ ATPase and exchanged with NCX § Contraction begins within milliseconds after the action potential arrives § Contraction ends a few milliseconds after the action potential ends § Duration of contraction is a function of the duration of the action potential including the Dr. Pasan Fernando plateau phase 53  Dr. Pasan Fernando 54  Intrinsic Conduction System Action potential initiation by pacemaker cells § Cardiac pacemaker cells have unstable resting membrane potentials called pacemaker potentials or prepotentials § Three parts of action potential 1. Pacemaker potential: K+ channels are closed, but slow Na+ channels are open, causing interior to become more positive 2. Depolarization: Ca2+ channels open (around -40 mV), allowing huge influx of Ca2+, leading to rising phase of action potential 3. Repolarization: K+ channels open, allowing efflux of K+, and cell becomes more negative Dr. Pasan Fernando 55  Intrinsic Conduction System – Activity in PACEMAKER Cells 1 Pacemaker potential This slow depolarization is due to both opening of Na+ Action Threshold channels and closing of K+ channels. Notice +10 Membrane potential (mV) potential that the membrane potential is never a flat line. 0 -10 2 2 -20 2 Depolarization The action potential 3 3 begins when the pacemaker potential reaches -30 threshold. Depolarization is due to Ca2+ influx -40 through Ca2+ channels. -50 1 1 -60 Pacemaker potential 3 Repolarization is due to Ca2+ channels -70 inactivating and K+ channels opening. This allows K+ efflux, which brings the membrane potential back to its most negative voltage. Time (ms) Dr. Pasan Fernando 56  Sinoatrial Node Action Potential SA Node § SA node cells depolarize between action potentials § Sit around -50 to -60 mV, partly because there are less potassium channels in SA node cells § Membrane slowly reaches to threshold § Depolarization is relatively slow SA node action potential § Has 3 phases § Phases are named based on the cardiomyocyte action potential Phase 4 – spontaneous depolarization Dr. Pasan Fernando Phase 0 – depolarization Phase 3 - repolarization 57  Phases in SA Node AP Phase 0 § L-type calcium channels open (slow kinetics) § few L-type calcium channels in nodal cells Phase 1 and 2 § no clear identifiable phase 1 or 2 Phase 3 § potassium channels open § Calcium channels deactivate, causes reduction in calcium current Phase 4 § Slow inward movement of Na+ causes slow Dr. Pasan Fernando depolarization 58  Ion Currents During the SA Node Action Potential SA node action potential Phase 4 – slow and spontaneous depolarization Phase 0 – depolarization Phase 3 – gradual repolarization Dr. Pasan Fernando 59  Dr. Pasan Fernando 60  Dr. Pasan Fernando 61