The Cardiovascular System: The Heart

1. The Cardiovascular System: The Heart • Heart pumps over 1 million gallons per year • Over 60,000 miles of blood vessels

2. Heart Location • Apex - directed anteriorly, inferiorly and to the left • Base - directed posteriorly, superiorly and to the right • Anterior surface - deep to the sternum and ribs • Inferior surface - rests on the diaphragm • Right border - faces right lung • Left border (pulmonary border) - faces left lung • Heart is located in the mediastinum

3. Pericardium • Fibrous pericardium • dense irregular CT • protects and anchors the heart, prevents overstretching • Serous pericardium • thin delicate membrane • contains: • parietal layer - outer layer • pericardial cavity with pericardial fluid • visceral layer (epicardium) • Epicardium • visceral layer of serous pericardium • Myocardium • cardiac muscle layer is the bulk of the heart • Endocardium • chamber lining & valves

4. Myocardium – cardiac muscle • shares structural and functional characteristics with skeletal muscle • striated • thin filaments contain troponin and tropomyosin – regulates cross-bridge formation • possess a definitive tension-length relationship • plentiful mitochondria and myoglobin • well-developed T-tubule structure

5. Myocardium – cardiac muscle • Also shares structural and functional characteristics with smooth muscle • calcium entry from the ECF triggers its release from the sarcoplasmic reticulum • displays pace-maker activity – initiates its own APs without external influence • interconnected by gap junctions (intercalated discs) – enhance the spread of APs • innervated by the ANS • unique – cardiac muscle fibers are joined in a branching network • action potentials last longer than skeletal before repolarization

6. Heart Anatomy Review

7. Right Ventricle Right Atrium • Receives blood from 3 sources • superior vena cava, inferior vena cava and coronary sinus • Interatrial septum partitions the atria • Fossa ovalis is a remnant of the fetal foramen ovale • Tricuspid valve • separates right atrium from right ventricle • has three cusps • Forms most of anterior surface of heart • Papillary muscles are cone shaped & raised bundles of cardiac muscle • Chordae tendineae: cords linking valve cusps to papillary muscles • Interventricular septum: partitions ventricles • Pulmonary semilunar valve: blood flows through this valve into pulmonary trunk

8. Left Ventricle Left Atrium • Forms the apex of heart • Chordae tendineae anchor bicuspid valve to papillary muscles • Aortic semilunar valve: • blood passes through this valve into the ascending aorta • just above valve are the openings to the coronary arteries • Forms most of the base of the heart • Receives blood from lungs - 4 pulmonary veins (2 right + 2 left) • Bicuspid valve: separates left atrium from left ventricle • has two cusps • to remember names of this valve, try the pneumonic LAMB • Left Atrioventricular, Mitral, or Bicuspid valve

9. Atrioventricular Valves • A-V valves open and allow blood to flow from atria into ventricles whenventricular blood pressure is lower than atrial pressure • occurs when ventricles are relaxed, chordae tendineae are slack and papillary muscles are relaxed • A-V valves close when ventricular blood pressure is higher than atrial pressure • chordae tendinae of the AV valves prevent backflow of blood into atria • ventricles contract, pushing valve cusps closed, chordae tendinae are pulled taut and papillary muscles contract to pull cords and prevent cusps from everting

10. Semilunar Valves • SL valves open with ventricular contraction/increased ventricular blood pressure • allow blood to flow into pulmonary trunk and aorta • SL valves close with ventricular relaxation • prevents blood from returning to ventricles

11. Blood Circulation Routes • Systemic circulation: left side of heart pumps blood through body • left ventricle pumps oxygenated blood into aorta • aorta branches into many arteries that travel to organs • arteries branch into many arterioles found in tissue • arterioles branch into thin-walled capillaries for exchange of gases and nutrients • deoxygenated blood begins its return in venules • venules merge into veins and return to right atrium via the two vena cava • Pulmonary circulation: right side of heart pumps deoxygenated blood to lungs • right ventricle pumps blood to pulmonary trunk • pulmonary trunk branches into pulmonary arteries • pulmonary arteries carry blood to lungs for exchange of gases • oxygenated blood returns to heart in pulmonary veins

12. SVC/IVCRight Atrium(tricuspid valve)Right Ventricle Passage of Blood through the Heart Body (pulmonary semilunar valve) Pulmonary Artery Lungs Pulmonary Vein Left Atrium bicuspid (mitral) valve Body Left Ventricle Aorta (aortic semilunar valve)

13. Conduction System of Heart • two types of cardiac muscle cells • 1. contractile cells • 99% of cardiac muscle cells • Do mechanical work of pumping by contracting • Normally do not initiate own action potentials • 2. autorhythmic cells • Do not contract • Specialized for initiating and conducting action potentials responsible for contraction of working cells

14. Cardiomyocytes are joined via intercalated discs – region that joins two cardiac cells • site of the intermembrane junctions known as gap junctions and desmosomes

15. The Desmosome • abundant in tissues under considerable stress • formation of a protein-rich plaque inside the plasma membrane of each cardiomyocyte • plaques link to the underlying cytoskeleton within the cell • plaques are joined to each other by adhesion proteins – cadherins(require calcium for interaction)

16. The Gap Junction • two plasma membranes are connected by a “channel” made of specific proteins = connexons • two connexons join end to end to connect the cells & allow a free flow of materials from cell to cell • allow for the spread of electricity within each atrium and ventricle • Abundant between the autorhythymic cells

17. The Gap Junction • the atrial and ventricular contractile cells – block to electrical conduction from atria to ventricle!!! • also a fibrous skeleton the supports the valves – non-conductive • therefore a specialized conduction system must exist to allow the spread of electricity from atria to ventricles

18. Conduction System of Heart • SA node = 1. • cluster of cells in wall of right atria • begins heart activity that spreads to both atria • excitation also spreads to AV node • AV node = 2. • in atrial septum, transmits signal to bundle of His • AV bundle (bundle of His) = 3. • the connection between atria and ventricles • Bundle branches = 4. • for conduction of action potential through the interventricular septum • Purkinje fibers = 5. • large diameter fibers that conduct signals quickly into the ventricular contractile cells

19. 3 Conduction Pathways • 1. atrial conduction system/interatrial pathway – spread of electricity from right to left atrium ending in the left atrium • through gap junctions of the contractile cells

20. 3 Conduction Pathways • 2. internodal pathway – spread of electricity to the AV node via autorhythmic cells • Several pathways called internodal tracts • There is a slow spread through the AV node to allow for the complete filling of the ventricles before they are induced to contract = AV nodal delay

21. 3 Conduction Pathways • 3. ventricular conduction system (Purkinje system) – Bundle branches, Purkinje fibers, ventricular muscle • Results in the simultaneous contraction of all ventricular cells • BUT the Purkinje fibers do not connect with every ventricular contractile cell • so the impulse spreads via gap junctions through the ventricle muscle once it leaves the Purkinje fiber

22. Rhythm of Conduction System • various autorhythmic cells have different rates of depolarization to threshold – so the rate of generating an AP differs • SA node fires spontaneously 70-100 times per minute – has the fastest depolarization rate • AV node fires at 40-50 times per minute • If both nodes are suppressed Purkinje fibers fire only 20-40 times per minute • Artificial pacemaker needed if rate is too slow

23. failure of SA node blockage of transmission from SA through the AV node • Overall contraction rate is driven by the SA node – fastest autorhythmic tissue • AV node is necessary to link the atrial rate to ventricular rate • in some cases – the normally slow Purkinje fibers can become overexcited = ectopic focus • e.g. premature ventricular contraction (PVC) • occurs upon excess caffeine, alcohol, lack of sleep, anxiety and stress, some organic conditions

24. Cardiac excitation • efficient cardiac function requires three criteria: • 1. atrial excitation and contraction should be complete before ventricular excitation and contraction • 2. cardiomyocyte excitation should be coordinated to ensure each chamber contracts as a unit • 3. atria and ventricles should be functionally coordinated (2atria contract together, 2 ventricles contract together)

25. AP and contraction • Ca+ triggers the same series of events as seen in skeletal muscle • Troponin binds calcium - tropomyosin “shifts” off of actin to expose myosin-binding sites • Eventual cross-bridging • BUT – the amount of Ca+ release can directly affect the number of cross-bridges formed in cardiac muscleand can directly affect the strength of the contraction! • elevated extracellular Ca+ can increase the strength of contraction • refractory period of cardiac muscle is longer than skeletal muscle (250msec) • allows for the emptying of the chambers

26. Cardiac muscle action potentials: The autorhythmic cell • e.g. the SA node • Autorhythmic cells do NOT have typical voltage- gated Na+ channels !!!!! • two important events occur: • 1. decreased outward K+ current • opening of a non-specific ion channels that allows entrance of Na+ ions (F-type channels) • coupled to the constant influx of Na+ is a decreased leak of K+ outward • as the K+ outflow decreases – membrane constantly drifts toward threshold (doesn’t balance out the Na+ inward flow)

27. Cardiac muscle action potentials: The autorhythmic cell • 2. increased inward Ca+ current • T-type Ca+ channels(voltage-gated) open as the membrane drifts toward threshold • brief influx of Ca increases the depolarization – reach threshold • at threshold – L-type Ca channelsopen – slower voltage-gated channels • big influx of calcium – so the influx of calcium (rather than Na+) is what drives the membrane potential of a cardiac cell toward threshold and beyond • Membrane potential resets through the closing of these Ca2+ channels and the opening of voltage-gated K+ channels

28. Cardiac muscle action potentials: The autorhythmic cell

29. Cardiac muscle action potentials: The Contractile cell • action potentials in the contractile cells of the myocardium are initiated by the SA node and spread via gap junctions – induces an AP in the contractile cells • mechanism: • 1. almost “instantaneous” rising phase of depolarization – Na+ entry through voltage-gated channels (similar to neurons) = “fast” Na+ channels • open and close very rapidly • large influx of Na+ is observed

30. Cardiac muscle action potentials: The Contractile cell • the plateau phase of a ventricular contractile cell is longer than an atrial cell • 2. Na+ permeability decreases significantly as the Na+ channels close • coupled to the opening of special class of K+ channels that open for a short period of time • this could cause repolarization - BUT there is a delay in repolarization • 3. the membrane potential instead of rapidly returning to negative is held positive for an extended period of time = plateau phase • result of the opening of “slow” L-type voltage-gated Ca+ channels in T-tubules • prolongs the positivity inside the cell 4. rapid falling phase eventually results – closing of Ca+ channels + the delayed opening of the typical voltage-gated K+ channels (similar to neurons and skeletal muscle)

31. L-type Ca+ channel SR SR SR Cardiomyocyte “anatomy” SR • The T-tubule system is for the conduction of the action potential deep inside the cardiomyocyte • runs in between adjacent sarcomere Z lines • The T-tubule is flanked on both sides by the sarcoplasmic reticulum • The passage of the action potential through a T-tubule causes the release of calcium from the sarcoplasmic reticulum

32. Calcium and cardiomyocyte contraction • “slow” L-type Ca+ channels (i.e. dihydropyridine receptors) are found within the T-tubules • the AP travelling down the T-tubule opens these L-type channels • triggers the opening of Ca+ channels within the adjacent lateral sacs of the sarcoplasmic reticulum • known as ryanodine or foot proteins • opening results from the physical interaction between the dihydropyridine receptors with their ryanodine “partners” • the AP travelling down the T-tubule opens the ryanodine/Ca2+ channels – which then opens the Ca2+ channels in the sarcoplasmic reticulum • “Ca-induced Ca release”

33. AP and contraction • Ca+ triggers the same series of events as seen in skeletal muscle • troponin binds calcium • tropomyosin “shifts” off of actin to expose myosin-binding sites • cross-bridging • the slow uptake of calcium back up into the SR prolongs the duration of the cross-bridging and contraction • PLUS the amount of Ca+ released can directly affect the number of cross-bridges formed in cardiac muscleand can directly affect the strength of the contraction! • elevated intraccellular Ca+ can increase the strength of contraction • refractory period of cardiac muscle is longer than skeletal muscle (250msec) • allows for the emptying of the atria and ventricles

35. Atrial systole and ventricular 2 diastole Atrial and 1 ventricular diastole 0.1 sec 0.3 sec 0.4 sec Ventricular systole and atrial 3 diastole Cardiac Cycle – for Anatomists • diastole – rest period • chambers are filling with blood • systole – pumping period • cardiac muscle contraction forces blood out under pressure • 1. Atrial and ventricular diastole • atria and ventricles are filling with blood • muscle is relaxed • 2. Atrial systole/ventricular diastole • contraction of atria forces blood into ventricles • 3. Ventricular systole/atrial diastole • ventricular contraction forces blood out of lungs and body • atria start to fill again

36. Here’s your cardiac cycle!UGH! https://commons.wikimedia.org/wiki/File:Cardiac-Cycle-Animated.gif#/media/File:Cardiac-Cycle-Animated.gif

37. Cardiac cycle • A. Midventricular diastole • 1. left atrium and ventricle are both in diastole (relaxed) & atria is filling with blood  increase in atrial blood pressure • 2. increase in atrial blood pressure opens the AV valve • 3. throughout diastole, the aortic semilunar valve is closed because aortic BP > ventricular BP • 4. as the blood flows through the aorta the aortic BP decreases

38. Cardiac cycle • A. Late ventricular diastole • 5. ventricular blood volume is increasing as blood enters from the atrium • 6. the SA node fires  P wave on the EKG • 7. resulting contraction of atrium significantly increases atrial BP • 8. increased atrial pressure forces more blood into the ventricle – increasing ventricular blood volume and BP • 9. volume in the ventricle at the end of diastole = end-diastolic volume or EDV (135ml)

39. Cardiac cycle • D. Start of ventricular systole • 10. ventricular systole begins with ventricular excitation = QRS complex • the electrical impulse has left the AV node and enters the ventricular musculature = ventricular contraction • 11. ventricular contraction produces a rapid increase inventricular pressure • 12. ventricular BP > atrial BP & the AV valve closes • 13. because aortic BP is still greater than ventricular BP the aortic semilunar valve remains closed

40. Cardiac cycle • E. isovolumetric ventricular contraction • just after the closing of the AV valve there is a brief moment where the ventricle is a closed chamber = isovolumetric ventricular contraction (first vertical blue bar) • ventricular pressure continues to rise dramatically (11) but the volume within the ventricle does not change – still at EDV (9)

41. Cardiac cycle • F. Ventricular ejection • 14. ventricular BP will now exceed aortic BP • 15. increased ventricular BP opens the aortic semi-lunar valve and the ventricle empties = ventricular ejection • 16. ventricular volume decreases as blood is ejected from the ventricle into the aorta • ejection is rapid and then slows • the volume of blood ejected – stroke volume (SV) • 17. the amount of blood remaining in the ventricle once ejection is complete = end-systolic volume or ESV (70ml) • the amount of blood ejected is called stroke volume (ESV – EDV = 65ml)

42. Cardiac cycle • F. Ventricular ejection • 18. the ejection of blood into the aorta temporarily increases its pressure and the aortic pressure curve rises and then falls as blood continues into and through the aorta • ventricular pressure also continues to rise during the 1st part of the ejection phase as the contraction force increases to ensure maximum stroke volume • 19. peak aortic and ventricular BP is reached before the end of the ejection phase – strength of ventricular contraction drops toward the end of the ejection phase • 20. decrease in ventricular volume slows as blood reaches complete ejection • 21. ventricular BP starts to decrease

43. Cardiac cycle • G. Ventricular repolarization • 22. T wave • 23. as the ventricle relaxes – ventricular pressure falls below aortic and the aortic SL closes • this closure produces a small disturbance in the aortic pressure curve – dicrotic notch

44. Cardiac cycle • H. Isovolumetric ventricular relaxation – Start of Ventricular Diastole • 24. all valves are closed because ventricular BP still exceeds atrial BP • the ventricle relaxes but blood volume remains the same (ESV – see 17) • known as isovolumetric ventricular relaxation (2nd vertical blue bar) • ventricular pressure continues to drop sharply (23)

45. Cardiac cycle • I. Ventricular filling • 25. isovolumetric ventricular relaxation ends when ventricular BP falls below atrial BP • atrial BP increases because the atrium continues to fill all during the cardiac cycle – except when in systole • 26. as atrial BP pressure exceeds ventricular BP – the AV valve opens again • 27. ventricular filling starts again increasing ventricular volume • 28. the filling is enhanced during the initial phase because ventricular BP decreases • the ventricle’s previous contraction produces an outward “recoil” that expands the size of the ventricle and decreases its BP further

46. closing valves during the cardiac cycle can be heard • sounds of heartbeat are from turbulence in blood flow caused by valve closure • first heart sound (lubb) is created with the closing of the atrioventricular valves • second heart sound (dupp) is created with the closing of semilunar valves Heart sounds & Ausculation

47. Stroke volume • SV = end-diastolic volume - end-systolic volume • SV = EDV- ESV • ESV –amount of blood left in a ventricle after systole • measured by EKG – end of the T wave • EDV –amount of blood in a ventricle after filling • measured using MRI, CT scan or a ventriculography (catheter in the ventricle and injection of an X-ray visible dye) • two major factors influence SV: • 1. Intrinsic control • 2. Extrinsic control

48. Intrinsic Control of Stroke Volume • heart’s inherent ability to vary SV • as more blood returns to the heart, the heart pumps out more blood • so the heart will pump what it is given • there is a direct relationship between EDV and SV • SV will increase as EDV increases • EDV is often referred to as pre-load = the volume of blood in the ventricle just prior to contraction • relationship between SV and EDV = Frank-Starling mechanism or Starling’s law Stroke Volume 110 ml

49. Frank-Starling Mechanism • for skeletal muscle –when muscle length is less than or greater than optimal length/lo– muscle contraction is weak • for cardiac muscle – resting cardiac muscle length is already less than lo • SO - increasing cardiac muscle length towards lo increases contractile tension • therefore filling the ventricle with more blood stretches the cardiac muscle and increases the resultant force of contraction • as the cardiac cell is stretched - myofilaments are pulled closer together • allows more cross-bridge formation

50. Extrinsic Control of Stroke volume • sympathetic & parasympathetic control • sympathetic nerves supply the entire myocardium • sympathetic NT norepinephrine binds beta-adrenergic receptors and increases the strength of contraction at any EDV