29. cardiovascular 1-08-09


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29. cardiovascular 1-08-09

  2. 2. CARDIOVASCULAR FUNCTION <ul><li>Cardiovascular function reflects the properties both of the different blood vessels, which make up the circulation and of the heart, which pumps blood through those vessels. </li></ul><ul><li>Cardiac physiology depends on the electrical and mechanical properties of cardiac cells, and on their integrated activity. As a result, the output from the heart can be varied to meet changing tissue needs. </li></ul><ul><li>Peripheral blood flow depends, both on the arterial pressure generated by the heart and on local resistance to flow. </li></ul>
  3. 3. COMPONENTS OF THE CIRCULATION <ul><li>The cardiovascular system consists of a heart, and two functionally distinct circulations, systemic and pulmonary. </li></ul><ul><li>Blood flow through the systemic circulation depends on contraction of the left ventricle of the heart, which forces blood into the aorta. </li></ul><ul><li>Large arteries branch off this to supply different areas of the body, forming regional circulations. </li></ul><ul><li>Within each tissue arterial vessels are arranged in series, terminating in the arterioles, which supply the tissue capillaries. These act as the sites of gas and nutrient exchange between blood and the interstitial fluid. </li></ul><ul><li>Capillaries drain through venules into veins, which empty in turn into the superior and inferior venae cavae, which return systemic blood to the right atrium. </li></ul>
  4. 5. COMPONENTS OF THE CIRCULATION <ul><li>The right side of the heart drives blood through the pulmonary circulation. The right ventricle fills from the right atrium and then contracts, driving blood into the pulmonary trunk, which supplies the pulmonary arteries. </li></ul><ul><li>Pulmonary capillaries lie in close contact with the air-filled alveoli of the lung and are involved in the gaseous diffusion, which oxygenates the blood. </li></ul><ul><li>The pulmonary veins return this oxygenated blood to the left atrium, which empties into the left ventricle, thus completing the double circulation. </li></ul>
  5. 7. CARDIAC STRUCTURE <ul><li>Heart is a double pump arranged as a muscular cone with its apex directed downwards and to the left and its base behind the upper sternum. Each pumping unit consists of two chambers, with a thin-walled atrium opening into a more muscular ventricle. </li></ul><ul><li>Endocardium lines the inner surface of the muscular myocardium , which is covered in turn by the epicardium . The whole heart is surrounded by a tough, fibrous sac - the pericardium . </li></ul>
  6. 8. CARDIAC STRUCTURE <ul><li>Atrioventricular valves prevent back flow of blood from ventricles to atria. </li></ul><ul><li>On the right side, this valve has three cusps and is known as the tricuspid valve , while on the left it has two cusps and is called the mitral valve . </li></ul><ul><li>There are also one-way semilunar valves at the ventricular outlets, where blood flows into the pulmonary trunk ( pulmonary valve ) or aorta ( aortic valve ). </li></ul>
  8. 10. CARDIAC MUSCLE CELLS <ul><li>The muscle cells (also known as cardiomyocytes or cardiac fibres) of the heart contain contractile proteins. </li></ul><ul><li>Cardiac muscle is rich in mitochondria, reflecting its dependence on aerobic metabolism, and the cells contain only one nucleus. </li></ul><ul><li>The fibres may branch at either end and they connect with the next cell in series through a region of close cellular association known as an intercalated disc . Desmosomes link the membranes of adjacent cells at these sites. </li></ul>
  9. 11. CARDIAC MUSCLE CELLS <ul><li>There are also special transmembrane channel proteins, which form gap junctions connecting the cytoplasm of the cells on either side of the intercalated discs. </li></ul><ul><li>This provides electrical continuity from cell to cell allowing easy transmission of action potentials. </li></ul><ul><li>Because of this the heart behaves as a functional syncytium , with rapid conduction of electrical signals leading to well-coordinated contraction. </li></ul>
  10. 12. CARDIAC ACTION POTENTIALS <ul><li>Cardiac muscle cells are excitable, and the signal, which leads to each contraction, is the generation of an action potential at the cell membrane. </li></ul>
  11. 13. CARDIAC ACTION POTENTIALS <ul><li>The resting membrane potential of the ventricular cells is similar to that in skeletal muscle (but more negative than that in nerve) at about -90 mV . </li></ul><ul><li>Depolarization of the membrane to threshold leads to the production of an “all or none” action potential with a characteristic shape. </li></ul><ul><li>There is an initial rapid depolarization to about +20 mV followed by an initial, partial repolarization of some 5-10 mV . </li></ul><ul><li>Further repolarization is very slow indeed and this produces an action potential plateau in which membrane potential remains close to 0 mV for some 150-300 ms. </li></ul><ul><li>After this, the membrane repolarizes rapidly , returning to the resting potential. </li></ul>
  12. 15. CARDIAC ACTION POTENTIALS <ul><li>The plateau greatly prolongs the action potential. This has important functional consequences for the mechanical activity of the heart. </li></ul><ul><li>Cardiac cells are absolutely refractory to stimulation for the whole duration of the action potential and show a high degree of relative refractoriness for an additional 50 ms. </li></ul><ul><li>Therefore, a second action potential cannot be generated for a period of up to 350 ms after stimulation in ventricular cells. </li></ul>
  13. 17. CARDIAC ACTION POTENTIALS <ul><li>Contraction and relaxation are complete within this time and so it is impossible to get summation of contractions, or continuous tetanic contractions. </li></ul><ul><li>Since effective cardiac pumping depends on cyclical contraction and relaxation, the prolonged action potential protects against pump failure caused by sustained contraction, which would prevent the heart from refilling. </li></ul><ul><li>It also sets an upper limit on the rate of contraction, which cannot exceed about 3-4 beats/sec in the ventricle. </li></ul><ul><li>Atrial rates can be considerably higher, however, because the atrial action potential and therefore the refractory period is shorter (less than 200 ms). </li></ul>
  14. 19. MECHANISM OF THE CARDIAC ACTION POTENTIAL <ul><li>The mechanisms underlying the cardiac action potential are similar to those in nerve, i.e. they depend on transmembrane ion gradients and voltage-sensitive changes in membrane permeability, or conductance, to those ions. </li></ul><ul><li>Three ions: Na, Ca and K are involved. </li></ul>
  15. 20. SODIUM CHANNELS <ul><li>Depolarization first opens (activates) Na channels, increasing Na conductance. </li></ul><ul><li>This leads to an inward Na current, which causes further depolarization. The resulting positive feedback accounts for the initial rapid depolarization phase. </li></ul><ul><li>Sodium conductance then declines again because of depolarization-induced inactivation of Na channels. </li></ul><ul><li>The cell remains refractory to stimulation until these have returned to their resting, closed state following repolarization. </li></ul>
  16. 21. CALCIUM CHANNELS <ul><li>Ca channels in the membrane open in response to depolarization. </li></ul><ul><li>They activate more slowly than the Na channels but once open they allow Ca to flow into the cell. </li></ul><ul><li>This inward Ca current keeps the membrane depolarized and thus maintains the plateau in the action potential. </li></ul>
  17. 22. POTASSIUM CHANNELS <ul><li>Potassium conductance first decreases following depolarization, so that during the plateau there is actually less outward K current than normal. </li></ul><ul><li>This makes it easier for the inward Ca current to maintain depolarization, since there is very little current flowing in the opposite direction. </li></ul><ul><li>After 200 ms K conductance rises, increasing the outward current. This K current repolarizes the membrane. </li></ul>
  18. 24. CARDIAC CONTRACTION <ul><li>The cellular basis of contraction is essentially the same as in skeletal muscle, with thick and thin myofilaments sliding past one another because of the formation of mobile cross bridges between myosin and actin. </li></ul><ul><li>Cross bridge formation is regulated by intracellular Ca so that increases in the cytoplasmic Ca lead to contraction through changes in the shape of the troponin-tropomyosin system on the thin myofilaments. The event which triggers contraction is the action potential. </li></ul><ul><li>In cardiac muscle this stimulates Ca release from the sarcoplasmic reticulum but the mechanism differs from skeletal muscle, in which Ca release is activated directly by membrane depolarization. </li></ul><ul><li>In the heart, Ca entry during the plateau phase of the action potential is the important stimulus, but the effect of this influx on the intracellular Ca is amplified by Ca, induced Ca release from the cardiac sarcoplasmic reticulum. </li></ul><ul><li>Once the plasma membrane has repolarized, Ca is rapidly removed from the cytoplasm (both by transport across the plasma membrane and reuptake into the sarcoplasmic reticulum), and the cell relaxes. </li></ul>
  19. 25. SPONTANEOUS ELECTRICAL ACTIVITY (AUTOMATICITY) <ul><li>An isolated heart beats regularly without any extrinsic stimulation from nerves or hormones ( mechanical automaticity ) . Such activity is myogenic (unlike action potentials in skeletal muscle, which are neurogenic). </li></ul><ul><li>The cells responsible for spontaneous action potential production are pacemaker cells because they determine the rate at which the heart beats. </li></ul><ul><li>Instead of a constant resting membrane potential between action potentials, there is a steadily depolarizing potential known as a pacemaker potential. </li></ul><ul><li>When threshold is reached an action potential fires, then the cycle of events is repeated. </li></ul>
  20. 27. SPONTANEOUS ELECTRICAL ACTIVITY (AUTOMATICITY) <ul><li>Several cell types in the heart are capable of pacemaker activity. </li></ul><ul><li>Normally the pacemaking frequency is highest in a group of specialized cells called the sinoatrial node, which also have a different shape of action potential. </li></ul><ul><li>These cells dictate the rate of electrical events in the rest of the heart. </li></ul><ul><li>This produces a resting heart rate of 60-70 beats/min, and the regular pattern of excitation and contraction which results is called sinus rhythm. </li></ul>
  21. 29. CONDUCTING PATHWAYS IN THE HEART <ul><li>Cardiac action potentials normally originate in the pacemaker cells of the sinoatrial node, which is located in the wall of the right atrium close to the superior vena cava. </li></ul><ul><li>Action potentials are conducted away from the sinoatrial node through the normal atrial fibers. </li></ul><ul><li>The conduction velocity through the atrial muscle is 0.3 m/s and this is rapid enough to produce a coordinated atrial contraction, which forces blood into the ventricles. </li></ul>
  22. 31. CONDUCTING PATHWAYS IN THE HEART <ul><li>The atrioventricular node is located on the atrial septum in the lower half of the right atrium. It consists of specialized conducting tissue which is capable of pacemaker activity but is normally driven by conducted action potentials from the sinoatrial node. </li></ul><ul><li>Conduction through the atrioventricular node is slow (about 0.05 m/s) and this delays transmission of the action potential to the ventricle, ensuring that ventricular contraction will not commence until atrial contraction is completed. </li></ul>
  23. 33. CONDUCTING PATHWAYS IN THE HEART <ul><li>Action potentials are conducted from the atria to the ventricles by the atrioventricular bundle, or bundle of His. </li></ul><ul><li>This divides into right and left bundle branches, and these carry the impulses down either side of the ventricular septum towards the apex of the heart. </li></ul><ul><li>These branches are continuous with the Purkinje fibers, which ramify through the ventricular muscle itself. </li></ul><ul><li>Conduction through the atrioventricular bundle, the bundle branches and the Purkinje fibres is rapid (2-4 m/s) and this promotes synchronized contraction throughout the muscle of the ventricles. </li></ul>
  24. 35. CARDIAC CONTRACTILE FORCE ( Starling's law ) <ul><li>Starling's law of the heart states that the energy produced by the heart when it contracts is a function of the end-diastolic length of its muscle fibers. </li></ul><ul><li>The Frank-Starling mechanism is extremely important in balancing the output of the two sides of the heart over extended periods. </li></ul>
  25. 36. FRANK-STARLING EFFECT <ul><li>One of the major factors that controls the force of cardiac contraction is the initial length (i.e., the preload) of the muscle fibers. </li></ul><ul><li>The preload depends on the volume of blood in the ventricles at the onset of contraction (VEDV). </li></ul><ul><li>The VEDV is considered to be proportional to either the VEDP or the central venous pressure (which are essentially equivalent). </li></ul>
  26. 38. FRANK-STARLING EFFECT <ul><li>Increases in preload raise the number of available cross-bridges by changing the overlap of the actin and myosin filaments. </li></ul><ul><li>1) The strength of the cardiac contraction is proportional to the number of available cross-bridges. </li></ul><ul><li>2) An increase in preload (or venous pressure) produces a stronger contraction, allowing the heart to pump more blood per beat. </li></ul>
  27. 39. INCREASED CONTRACTILITY (positive inotropism) <ul><li>Changes in stroke volume also depend on the contractility of the ventricles. </li></ul><ul><li>Increased contractility (positive inotropism) is a greater contractile force at a constant preload or ventricular volume. </li></ul><ul><li>Positive inotropism allows the ventricles to eject more blood from the same diastolic volume; consequently, the stroke volume increases. </li></ul>
  28. 40. POSITIVE INOTROPIC MECHANISMS <ul><li>1) Activation of the beta1-receptors (via sympathetic nerve stimulation) increases the concentration of Ca within the myocardial cells and results in a more rapid and forceful contraction. In addition, the Ca is taken up more rapidly by the sarcoplasmic reticulum, which shortens the duration of both the action potential and the contraction. </li></ul><ul><li>2) Digitalis glycosides (e.g. digoxin) also increase the force of cardiac contraction by raising the intracellular Ca concentration. </li></ul>
  29. 41. POSITIVE INOTROPIC EFFECTS <ul><li>A greater stroke volume (more cardiac force) can be generated at a constant ventricular volume, or the same force can be generated from a smaller VEDV. </li></ul>
  30. 42. MAXIMAL VELOCITY OF SHORTENING <ul><li>Positive inotropism also can be defined as an increase in the maximal velocity of shortening when it is plotted as a function of afterload. For the ventricles, the afterload is the arterial pressure during the ejection phase. During any muscle contraction, the velocity of shortening and the force developed are inversely related. </li></ul><ul><li>1) The intercept of each line with the x-axis represents the load that prevents shortening of the muscle fibers. This condition is referred to as an isometric or isovolumic contraction. </li></ul><ul><li>2) Increased contractility allows the ventricle to generate a greater amount of force from the same preload (venous pressure or VEDV). </li></ul><ul><li>This contrasts with the Frank-Starling mechanism, where an increase in the force of contraction is produced by an increase in fiber length or preload. </li></ul>
  31. 43. DECREASED CONTRACTILITY (negative inotropism) <ul><li>Negative inotropism represents a decrease in the force of contraction at any fiber length or ventricular volume. </li></ul><ul><li>This condition results from hypoxia, acidosis, myocardial ischemia, or infarction. </li></ul>
  32. 44. DECREASED CONTRACTILITY (negative inotropism) <ul><li>1) The damaged or dead tissue leads to a decrease in stroke volume and a decline in cardiac output. The decreased pumping ability of the ventricle results in an increase in ventricular size as the venous pressure increases. </li></ul><ul><li>2) The increased ventricular volume invokes the Frank-Starling mechanism , increasing the force of contraction and returning the stroke volume toward normal. </li></ul><ul><li>3) However, as the ventricle dilates, it faces a double disadvantage because of the Laplace effect. </li></ul>
  33. 45. Law of Laplace <ul><li>For a thick-walled structure such as the ventricle, the law of Laplace can be expressed as: </li></ul><ul><li>T = (P x r)/ h, </li></ul><ul><li>where: </li></ul><ul><li>T - wall tension, </li></ul><ul><li>P - pressure difference across the ventricular wall, </li></ul><ul><li>r - radius of the ventricle, </li></ul><ul><li>h - ventricular wall thickness. </li></ul>
  34. 46. Law of Laplace <ul><li>1) Wall tension . Any hollow organ such as the ventricle generates pressure by increasing wall tension, which squeezes down on the contained volume. </li></ul><ul><li>2) Ventricular dilation causes a thinning of the ventricular wall because a given ventricular muscle mass must enclose a larger volume of blood. </li></ul><ul><li>3) Ventricular radius . Because ventricular dilation is equivalent to an increased ventricular radius, the ventricle must generate a greater wall tension to maintain any given force generation or systolic pressure (i.e., a larger ventricle must work harder to generate the same stroke volume). </li></ul>
  35. 48. THE CARDIAC CYCLE <ul><li>The cardiac cycle refers to the mechanical and electrical events during a single cycle of contraction and relaxation. </li></ul><ul><li>It describes both the patterns of change observed in individual measurements of mechanical and electrical function and how the timings of events in different chambers of the heart relate to each other. </li></ul>
  36. 50. MECHANICAL EVENTS: VENTRICULAR PRESSURE <ul><li>This is the simplest of the three relevant pressure waves. </li></ul><ul><li>During most of ventricular diastole, when the ventricle is relaxed, intraventricular pressure is low (less than 1 mm Hg). </li></ul><ul><li>This rises to about 5 mm Hg at the end of diastole because of atrial systole, which forces additional blood into the ventricle. </li></ul>
  37. 51. MECHANICAL EVENTS: VENTRICULAR PRESSURE <ul><li>As the atrium relaxes, pressure falls but ventricular systole, or contraction, then commences and pressure rises rapidly, reaching a peak of about 120 mm Hg in the left ventricle. </li></ul><ul><li>The wave form in the right ventricle is identical in shape to that in the left but the peak pressure during systole is much lower, at about 25 mm Hg. </li></ul><ul><li>Pressure falls back to its original low value as the ventricle relaxes (diastole). </li></ul>
  38. 52. MECHANICAL EVENTS: VENTRICULAR PRESSURE <ul><li>The cardiac cycle lasts 0.9 s (i.e. resting heart rate equals 66 beats/min), systole lasting 0.3 s and diastole 0.6 s. </li></ul><ul><li>As heart rate increases, it is mainly diastole which shortens, and if the heart rate rises too high, cardiac pumping becomes very inefficient because of inadequate ventricular filling during diastole. </li></ul>
  39. 54. ATRIAL PRESSURE <ul><li>There are three peaks in atrial pressure, known as the 'a', 'c' and 'v' waves. Throughout ventricular diastole there is a pressure gradient favouring blood flow through the open atrioventricular valve into the ventricle. </li></ul><ul><li>Atrial pressure remains constant, at about 1 mm Hg, until atrial systole, when active atrial contraction raises it to a peak of about 6 mm Hg. This is the 'a' wave. </li></ul>
  40. 55. ATRIAL PRESSURE <ul><li>The atrium then relaxes and ventricular pressure starts to rise so the atrial and ventricular pressure curves cross each other. This reverses the pressure gradient and, as a result, the atrioventricular valve (which only permits flow from atrium to ventricle) closes. </li></ul><ul><li>The back pressure on the valve cusps during early ventricular systole, when both the inflow and outflow valves of the ventricles are closed, causes a secondary rise in atrial pressure, the 'c' wave. </li></ul>
  41. 56. ATRIAL PRESSURE <ul><li>As soon as the aortic or pulmonary valves open, atrial pressure falls rapidly to almost zero. Blood continues to enter the atria from the venous system, however, and since the atrioventricular valves are closed this produces a steady increase in pressure, the 'v' wave. </li></ul><ul><li>This peaks at 3-4 mm Hg just before the rapidly falling pressure in the relaxing ventricle drops below that in the atrium. The atrioventricular valves reopen and the atrial pressure drops back to about 1 mm Hg. </li></ul>
  42. 58. AORTIC PRESSURE <ul><li>During ventricular diastole, there is a gradual decline in aortic pressure to a minimum of about 80 mm Hg. Throughout this period, aortic pressure is higher than left ventricular pressure so the aortic valve remains closed. </li></ul><ul><li>During systole, the ventricular pressure rises above aortic pressure, opening the valve and allowing blood to be ejected into the aorta. Aortic pressure follows ventricular pressure closely during systole, peaking at about 120 mm Hg, but as the pressure in the ventricles starts to decline there is a much slower drop in aortic pressure. </li></ul>
  43. 59. AORTIC PRESSURE <ul><li>This reflects the elasticity of the aorta, which is stretched by the rapid inflow of blood during ventricular systole. The stored elastic energy is then released during diastole, as the walls of the aorta passively recoil, thus maintaining aortic pressure. </li></ul><ul><li>As a result, the aortic and ventricular pressure waves cross once more, and the aortic valve closes. </li></ul><ul><li>This halts the back flow of blood towards the ventricle and the force generated as the momentum of this blood is dissipated shows up as a brief increase in aortic pressure; the dicrotic notch. </li></ul>
  44. 60. PULMONARY TRUNK PRESSURE <ul><li>Pressures in the pulmonary trunk follow a similar pattern but are much lower at 25/10 mm Hg as compared with 120/80 mm Hg for the aorta (systolic/diastolic pressure). </li></ul><ul><li>This reflects the lower resistance of the pulmonary circulation; pulmonary and systemic blood flow being almost equal. </li></ul>
  45. 61. HEART SOUNDS <ul><li>Closure of the valves of the heart produces mechanical vibrations which are audible at the chest wall as the heart sounds. </li></ul><ul><li>The first heart sound is caused by the closure of the atrioventricular valves and so marks the beginning of ventricular systole. </li></ul><ul><li>The second heart sound is caused by closure of the aortic and pulmonary valves. </li></ul>
  46. 63. VENTRICULAR VOLUME <ul><li>At the end of systole, there is about 70 ml of blood in the ventricle. </li></ul><ul><li>This increases to about 125 ml during diastole as a result of passive filling from the atrium. </li></ul><ul><li>Active filling during atrial systole at the end of ventricular diastole only increases filling by a further 25%, to about 140 ml. </li></ul><ul><li>The dominance of passive filling explains why ventricular function is still possible in the absence of coordinated atrial contraction ( e.g. during atrial fibrillation ) . </li></ul>
  47. 64. VENTRICULAR VOLUME <ul><li>Following closure of the atrioventricular valve, but before the aortic valve opens, the ventricles are effectively closed boxes whose volume cannot change. </li></ul><ul><li>There is, therefore, a short period of isovolumetric contraction, with constant volume but rising ventricular pressure. </li></ul><ul><li>Opening of the aortic valve then leads to the ejection phase during which ventricular volume drops from 140 ml to 70 ml. Therefore, about 70 ml of blood are ejected in each cycle, i.e. the stroke volume is 70ml. </li></ul><ul><li>Ejection is followed by a period of isovolumetric relaxation during which atrioventricular and aortic valves are again closed. Passive filling then recommences with opening of the atrioventricular valve. </li></ul>
  48. 66. CLINICAL SIGNIFICANCE <ul><li>1. Diminished cardiac reserve. </li></ul><ul><li>Decreased contractility means that the ability of the heart to increase the stroke volume is limited; therefore, cardiac output is primarily maintained by increasing the heart rate . </li></ul><ul><li>Patients' ability to increase cardiac output in response to stress is limited, causing them to tire easily. </li></ul><ul><li>Eventually, the compensatory mechanisms fail, and cardiac output further declines. </li></ul>
  49. 67. CLINICAL SIGNIFICANCE <ul><li>2. Edema, in severe ventricular failure , VEDP is high. Increased VEDP raises venous pressure, which is reflected back to the capillaries and produces leakage of fluid into the tissues (edema). </li></ul><ul><li>a) In left-sided heart failure , fluid accumulates in the lungs, causing difficulty breathing (dyspnea) and the inability to breathe when lying down (orthopnea). </li></ul><ul><li>b) In right-sided heart failure , dependent edema occurs in the feet and ankles, because the high venous pressures are reflected into the systemic capillaries. </li></ul>
  50. 68. CLINICAL SIGNIFICANCE <ul><li>3. Hypertrophy . Any increase in the work of the heart causes the ventricular muscle to enlarge, like any other muscle that is exercised sufficiently. </li></ul><ul><li>a) The ventricles first dilate, producing thinning of the wall; later the muscle hypertrophies. Myocytes have a limited ability to multiply; therefore, hypertrophy entails an increase in the diameter of the muscle fibers. </li></ul><ul><li>b) The increased muscle dimensions may cause ischemia because the diffusion distance between capillaries increases. The hypertrophy also may be harmful if the blood supply does not increase proportionately. </li></ul>
  51. 69. Thank You For Your Attention!