CARDIOVASCULAR PHYSIOLOGY FOR UNIVERSITY STUDENTS

1. CARDIOVASCULAR PHYSIOLOGYFOR UNIVERSITY STUDENTS S. I. OGUNGBEMI DEPARTMENT OF PHYSIOLOGY UNIVERSITY OF LAGOS

2. Cardiovascular System

3. INTRODUCTION • Cardiovascular system (CVS: aka circulatory system) consists of the heart and blood vessels. • The Heart • The heart is a muscular pump with 4 chambers. • The chambers are 2 atria and 2 ventricles. • The ventricles are the pumps arranged in series. • These pumps maintain continuous blood flow and blood perfusion round the body.

4. The Pump The Heart

5. The 2 pumps are left ventricle (LV) which pumps blood to systemic circulation and right ventricle (RV) which pumps blood to pulmonary circulation. • LV output = RV output = 5000 mL/min of blood. • Heart beats at 70-75 times per minute i.e. heart rate. • LV or RV output/beat = 70 mL i.e. stroke volume. • CVS circulates blood from the heart via a network of arteries, arterioles, capillaries to body tissues and • Drains blood from body tissues via venules, veins and vena cavae to the heart.

6. The Vessels (Vascular System)

7. Thoracic Aorta

8. Superior Vena Cava

11. Major Functions of the Cardiovascular System • Transport and supply of O₂ from the lungs to the body tissues. • Extraction and transport of CO₂ from the body tissues to the lungs. • Absorption and transport of nutrients (digested food, electrolytes and vitamins) from gastrointestinal tract to the body tissues. • Extraction and transport of waste and by-products of cellular metabolism from body tissues to excretory organs: kidneys, gut, liver, skin, lungs.

12. Transport of hormones from endocrine organs to target tissues/organs. • Distribution of body heat from body’s core to its surface, aiding temperature regulation. • Transport of red and white blood cells, immune factors, playing role in defense against foreign antigens, viruses, bacteria, parasites, fungi and cancer cells. • Perfusioning of the body tissues, aiding tissue hydration. • Functional Divisions of Circulatory System • Functionally, RV runs pulmonary circulation which is in series with LV that runs systemic circulation.

13. RV is a low pressure pump which receives deoxygenated blood from superior (SVC) and inferior (IVC) vena cavae via the right atrium. • RV pumps the blood via pulmonary trunk and arteries to pulmonary capillaries surrounding the alveoli. • The blood is then oxygenated and drained into the LV via left atrium and pulmonary veins. • This is the pulmonary circulation of low pressure belt of 25 (systolic) to 10 (diastolic) mmHg.

14. LV receives the oxygenated blood and pump it to the systemic circulation via aorta, large arteries arterioles and systemic capillaries to body tissues. • In returns, the capillaries, venules and veins then drain blood from the body tissues via SVC and IVC to the right atrium. • This is the systemic circulation of high pressure belt (SBP: 120 and DBP: 80 mmHg). • The heart, especially the RV and LV, provides the propulsive force as the pump for both pulmonary and the systemic circulations.

15. Structural Function of the Heart • The heart lies slantly in the thorax in the thorax as an inverted conoid. • The superior portion where blood vessels enter and leave the heart is the BASE. • The extremity of the left ventricle is the APEX. • The heart is a hollow muscular organ which weighs about 300 or 350 g in adults. • The heart muscle is specially called cardiac muscle. • The heart is made of 4 chambers: 2 atria and 2 ventricles which lie side-by-side in series.

16. It is divided by the septum into right and left portions. • The right portion comprises right atrium and right ventricle. • The left portion comprises left atrium and left ventricle. • It is also divided into 2 atria above and 2 ventricles below by 2 atrioventricular valves on both right and left sides. • There are 4 valves in the heart: 2 atrioventricular valves described above and 2 semilunar valves at the exits of aorta on the left and pulmonary trunk on the right. • The inlet (atrioventricular) valve and the outlet (semilunar) valve of each ventricle lie along side one another.

17. So, the 4 valves lie in the same plane in the septum separating the atria from the ventricles. • The 3 Layers of the Heart • The 3 layers of the heart are: • Endocardium • Myocardium and • Epicardium • Endocardium • It is the inner lining of the heart. • It continues with the endothelium (i.e. the lining of the blood vessels).

18. Myocardium • It is the muscular layer of the heart. • It is made up of conductive and contractile cardiac tissues. • Epicardium • It is a serous layer that function as the visceral layer of the pericardium. • Pericardium • It is the conical sac within which the heart lies. • It consists of inner serous pericardium and outer fibrous pericardium. • Inner serous pericardium composed of visceral (attaching the heart) and parietal (attaching the fibrous sac) layers.

19. These 2 layers allows the heart to beat in the mediastinum with minimum friction. • Pericardium sets a limit to the maximum size of the ventricles and prevents excessive stretching of the cardiac muscle fibres during ventricular filling (with blood). • It is attached to the diaphragm, fixing the apex during each heart beat. • Thus, during ventricular contraction the base and the atrioventricular ring descends towards the apex. • This arrangement increases the size of the atria for subsequent venous return as blood is ejected from the ventricles.

20. Cardiac Valves • Cardiac valves are thin flaps of flexible, endothelium covered fibrous tissues. • They are firmly attached at the base to the fibrous valve rings. • There are 2 types of valves: the atrioventricular (AV) valves and semilunar valves. • The AV valves are the right atrioventricular (tricuspid) valve and the left atrioventricular (bicuspid or mitral) valve. • Semilunar valves are the aortic and pulmonary arterial valves

21. All the 4 valves lie in the same plane in the fibrous septum which separates the atria from the ventricles. • The movements of these valves’ flaps are passive. • The valve ensure unidirectional flow of blood through the heart without backflow. • Blood Supply to the Heart • The right and left coronary arteries and their branches supply blood to the heart. • They are the 1st branches to the heart just above the aorta. • Coronary venous blood is drained by the coronary sinus which drains into the right atrium.

22. Nerve Supply to the Heart • Sympathetic and parasympathetic nerves supply the heart. • Parasympathetic fibres supply the atria, sinus node, AV-node and conductive tissue via vagus nerve. • Sympathetic nerves are from T₁ to T₄ via inferior cervical (stellate) ganglion. • The parasympathetic supplies slow down conduction speed and heart rate. • Sympathetic nerves speed up electrical conduction, heart rate and force of contraction.

23. The heart also possess some sensory fibres for cardiovascular reflexes and pain signals. • Function Histology of the Heart • The cardiac tissue are divided into conductive tissue and contractile tissue in the myocardium. • Conductive Tissue • The conductive tissue comprises special modified nerve cells that initiate and conduct rhythmic depolarisations of the myocardial cells. • These specialised tissues are: • Sinuatrial (SA) node

24. Internodal tracts • Atrioventricular (AV) node • Atrioventricular bundle of His • Purkinje fibres • SA Node is located in the wall of right atrium (beneath the epicardium) at superior vena cava and right atrium junction • It contains the pace-maker cells that originate depolarisation and each subsequent heart beat. • AV node lies beneath the endocardium of posterior wall of the right atrium about the insertion of the tricuspid valve. • The internodal tract connects the SA node to AV node.

25. These tracts are 3: • Anterior band of Bachmann • Middle band of Wenckebach • Posterior band of Thorel • The specialised conductive cells of AV node is arranged interiorly in a longitudinal fashion to form bundle of parallel fibers called AV bundle of His. • The bundle of His divides into the right and left bundle branches. • Purkinje fibres branch off from the main bundle and supply the myocardium.

26. Bundle branches and their smaller branches constitute a fast conduction pathway through which excitation impulses are rapidly spread throughout the heart. • The Contractile Tissues • A cardiac muscle cell is called myocardial fibre or cardiac myofibril • Histology of the myocardial tissue shows that myocardial fibre is striated as it is in skeletal muscle. • These fibres are cylindrical in shape with central nuclei. • In addition to this striations, myocardial fibres are interconnected into a latticework.

27. It is difficult to see where a cell ends and another begins. • Intercalated disc separate individual myocardial fibres. • Intercalated disc has electrical conductance of 400 units greater than that of ordinary cardiac muscle membrane, i.e. its resistance is ¼₀₀ unit of myocardial membrane. • The adjacent myocardial fibre membranes fuse with each other to form “tight junctions”. • These tight junctions allow complete free diffusion of ions in and out of the myocardial fibres. • Tight junction makes the entire myocardium contracts as if it were a large sheet of muscle – i.e. functional syncytium.

28. Action potentials from adjacent cardiac myofibrils are conducted speedily through the intercalated discs and tight junctions to all cardiac myofibrils. • This leads to depolarisation of the entire heart at once. • Subsequently, the entire ventricular myofibrils also contract in synchrony in order to develop adequate expulsive force to pump out blood. • The syncytial arrangement of myocardial fibres enables the contraction wave to rapidly spread from one myofibril to another until the whole ventricular mass contracts at once. • The detail histology of the heart is given under nerve-muscle physiology.

29. Note • No nerves are involved in the spread of contraction waves throughout the myocardium. • Evidence • It has been shown that series of interdigital cuts through a piece of atrial or ventricular muscle such that could severe any nerve running in it could not prevent synchronous contraction. • Despite the cuts, application of contraction waves at one part would spread through to the whole myocardial mass producing synchronous contraction.

30. Functional Structure of the Vessels • Blood vessels are arteries and veins • In addition, there are also lymphatic vessels. • In general circulation plan: • Aorta leads from the heart to supply blood and divides to become arteries. • Arteries then divide repeatedly to become arterioles. • Arterioles divide repeatedly to become capillaries. • Capillaries unite to become venules. • Venules unite to become veins. • Veins unite to become vena cava which then returns blood to the right atrium.

31. Arteries and veins have 3-layer walls: • Tunica intima • Tunica media • Tunica adventitia • Tunica intima is the innermost layer, composed of a super-smooth epithelium called endothelium which continues with endocardium of the heart. • Tunica media is the middle layer composed of smooth muscle • Tunica adventitia is the outermost layer of connective tissues.

32. Aorta and large arteries are blood distributing or conducting vessels, distributing oxygenated blood. • They have thinner wall of smooth muscle and larger wall of elastic tissues. • They are stretched during systole but are elastically recoiled during diastole. • The elastic recoil during diastole impacts momentum to the blood flow in the arteries (impact of 40 mm Hg). • The elastic recoil results in diastolic pressure of 80 mm Hg. • The stretch/recoil cycle provides continuous blood flow in circulation.

33. Arterioles contain thick layer of vascular smooth muscles. • These smooth muscles have sympathetic and parasympathetic innervations. • Smooth muscle responds to vasoactive agents like adrenaline, noradrenaline and acetylcholine • Arterioles are the major sources of peripheral resistance to blood flow in circulation. • Alterations of arteriolar radius bring about changes in peripheral resistance, blood pressure and blood flow. • R α ¹⁄r⁴ → R = ⁿ⁄r⁴: where R = peripheral resistance; r = arterial radius; n = constant.

34. Decrease in radius (vasoconstriction) increases peripheral resistance (R) while increase in radius (vasodilatation) decreases R of the arterioles. • Decrease in R increases flow (F) and vice versa • Increase in R or F increases mean arterial pressure (P) • Capillaries are the smallest vessels with diameter of about 8 μm. • They are one cell thick endothelial wall but just large enough for an RBC to pass through at once. • Capillaries are sites of exchange of substances between blood and tissue cells.

35. Filtration occurs at the arterial end of the capillaries (mostly O₂ and nutrients, ions, hormones) • Reabsorption occurs at the nervous end (removing CO₂, waste products and metabolites) • Veins are blood drainage vessels, draining and returning blood into the heart. • They return deoxygenated blood to the heart. • They are thinned-walled low pressure and cylindrical distensible vessels. • They are capacitance vessel containing about 75% of the entire circulating blood volume.

36. Some veins have one-way valves which prevent reflux of blood flow as they drain blood against gravity. • They possess sympathetic innervation which maintains the venomotor tone. • Venules are the smallest veins with less prominent muscular walls than those of arterioles.

37. PHYSIOLOGICAL PROPERTIES OF THE HEART • Physiological properties that are peculiar to cardiac tissues/cells are listed below as follow: • Spontaneous and automatic cardiac rhythmicity • Length-Tension relationship • Prolonged repolarisation of action potentials • Absolute refractoriness • Functional syncytium nature of cardiac myofibril • Obeys all or none law • Double innervation • Note: the 6th property is common to skeletal muscle or nerve cell and 7th property is common to some visceral tissues as well.

38. Length-Tension Relationship • If the length of a cardiac myofibril is increased, the force of contraction also increases. • Starling’s law states that the force of contraction of cardiac myofibril is proportional to its extension and initial length. • The initial length is the resting length before the extension of the cardiac myofibril or muscle fibre. • These fibres are extended by blood filling the ventricles i.e. blood volume exerts tensions on the heart muscle fibres. • In addition at resting length, these cardiac myofibrils assume sarcomere length for maximal contraction.

39. This extension by the filling blood volume stores up potential energy which is kinetiated into contraction (mechanical energy). • This energy from mas to ½κε² means mas = ½κε² • κ = extension constant • ε = extension of the myocardial fibre • m = mass of the myocardial fibre • a = acceleration of the myocardial fibre during contraction. • s = distance covered by the myocardial fibre during contraction.

40. The force of contraction is increased by positive inotropic agents like Ca²⁺, adrenaline, noradrenaline, thyroxine etc. • On the other hand, the force of contraction is reduced by negative inotropic agents like K⁺, acetylcholine etc. • Note • Excess Ca²⁺ will make the heart to stop working at systole (i.e. cardiac arrest at systole). • Excess K⁺ will make the heart to stop at diastole (i.e. cardiac arrest at diastole).

41. Spontaneous and Automatic myocardial Rhythmicity • Inherently, the heart is able to initiates its own electrical excitation, contraction and heart beat without nervous or humoral stimulation from any tissues outside itself. • So the cardiac myofibrils contract (at systole) and relax (at diastole) alternately in a rhythmic manner inherently. • Conductive tissues which produces spontaneous excitation and contraction are the source of this ability of the heart. • The conductive tissues are the SA and AV nodes, bundle of His and Purkinje fibres.

42. Prolonged Repolarisation • The action potential in the myocardial or contractile cells lasts about 300 msec unlike the 2 msec in skeletal muscle. • This is due to the fact that repolarisation phase of the action potential (AP) is prolonged in cardiac muscle cells. • Slow influx of Ca²⁺ or slow inward Ca²⁺ current is responsible for the prolonged repolarisation phase. • Ca²⁺ moves slowly inside cardiomyocytes to produce the plateau, resulting in persistent depolarisation during the prolonged repolarisation phase of cardiac AP • This persistent depolarisation is a positive membrane potential during repolarisation phase cardiac myocytes.

43. Ca²⁺ influx is via potential sensitive channels (PSC) of the cardiacmyocytes which opens during electrical excitation. • Ca²⁺ also flux in via receptor operated channels (ROC) which are sensitive to noradrenaline, adrenaline (agonists). • Influx of ISF Ca²⁺ stimulates the release of more Ca²⁺ᵢ from sarcoplasm reticulum which then induce cardiac muscle contraction. • Ca²⁺ channels blockers like verapramil or nifedipine inhibit Ca²⁺ entry following depolarisation of the myocardial cells.

44. Functional Syncytium Myofibrils • The cardial myocytes function like a syncytium. • Because the whole ventricular or atrial myofibrils contract at once as if they were one myofibril. • Cardiac myofibrils possess intercalated disc, tight and gap junctions which make them to contract as a syncytium. • Absolute Refractoriness • A second excitation cannot cause the cardial myocytes to depolarise or contract while the first excitation in process. • Therefore, the heart muscle cannot tetanise, because its action potential (AP) is prolonged and the period of contraction is as long as the duration of its AP.

45. The prolonged absolute refractoriness makes it impossible for the heart muscle to tetanise. • Obeys “All” or “None” Law • Cardiac myofibril does not possess graded excitation. • These myofibrils are only excited to produce an AP (“all” part of the rule) by a threshold or suprathreshold stimulus. • On the other hand, the myofibrils are not excited by subthreshold stimulus (the “none” part of the rule). • Cardiac myofibrils doesn’t exhibit recruitment of fibres with increase in stimulus strength unlike skeletal muscle.

46. CARDIAC ELECTROPHYSIOLOGY • Origin of the Heartbeat • The 2 atria and the 2 ventricles beat in orderly rhythm as atria systole is followed by ventricular systole. • Systole of atria and ventricles occurs one after the other respectively and is followed by diastole in orderly rhythm. • The heartbeat ORIGINATES in a specialised cardiac conducting system comprises modified nerve tissues. • The conductive system generates and transmits electrical current or action potential (AP) from one point to another and to all part of the myocardium.

47. The tissues that make up the conduction system are: • Sino-atria node (SA node) • 3 atria internodal pathways • Atrioventricular node (AV node) • Bundle of His and its branches • The Purkinje system • The SA node is the cardiac pacemaker, since it originates AP spontaneously and automatically and spread to all other conductive tissues and myocardium. • Other conductive tissues and myocardium are induced in this way to generate and transmit impulses.

48. SA node discharges AP most rapidly than AV node, conductive fibres and myocardial fibre. • SA node firing rate superimposes those of all others, making them to discharge at the same rate with SA node. • SA nodal rate equals heart rate as the pacemaker. • AP generated in the SA node spread through the atrial pathways to the AV node. • AV node then spread AP via His bundle and its branches. • Finally, AP is spread to the ventricular muscles (for contraction) via Purkinje fibres.

49. Origin and Spread of Cardiac Excitation • P (pacemaker) cells produce AP in the SA node. • They are small round cells (with few organelles) joined by gap junction and found in large population in SA node. • They are also found in AV node but in a lesser population. • SA nodal P cells send AP radially via the atria to converge on the AV node through: • Anterior internodal tract of Bachman • Middle internodal tract of Wenckebach • Posterior internodal tract of Thorel and • Slow atrial myofibrils.

50. The atrial depolarisation is complete within 0.1 s. • In the AV node, depolarisation is then sent to the ventricles with a slow conduction of 0.1 s delay. • Sympathetic stimulation hastens the conduction, shortening the delay while vagal stimulation lengthens the conduction, prolonging the delay. • Depolarisation waves then further spread from the top of interventricular septum in the Purkinje fibres rapidly to all parts of the ventricles within 0.08 – 0.10 s. • This depolarisation is so rapidly spread in the His bundle-Purkinje fibres and ventricular muscle mass.