Physiology 2 Muscle Сontractions

Steps in excitation-contraction coupling The term “excitation-contraction coupling” refers to the mechanism by which the action potential causes the myofibrils of muscle to contract (with some similarity between skeletal and cardiac muscles) 1. The action potential spreads from the cell membrane into the T tubules. 2. During the plateau of the action potential, Ca2+conductance is increased and Ca2+ enters the cell from the extra-cellular fluid (inward Ca2+current) through di-hydro-pyridine sensitive L-type Ca2+ channels. . Entry of small amount of Ca from ECF 3. This Ca2+entry trigger the release of even more Ca2+from the SR (Ca2+-induced Ca2+release) through ryanodine sensitive Ca2+ release channels. Release of large amount of Ca from endoplasmic reticulum causes (calcium sparks) The amount of Ca2+released from the SR depends on the amount of Ca2+previously stored and on the size of the inward Ca2+current during the plateau of the action potential. In this way, a small amount Ca2+ entering the cytosol from the ECF induces a much larger release of Ca2+ into the cytosol from the intracellular stores. Steps in excitation-contraction coupling The term “excitation-contraction coupling” refers to the mechanism by which the action potential causes the myofibrils of muscle to contract (with some similarity between skeletal and cardiac muscles) 1. The action potential spreads from the cell membrane into the T tubules. 2. During the plateau of the action potential, Ca2+conductance is increased and Ca2+ enters the cell from the extra-cellular fluid (inward Ca2+current) through di-hydro-pyridine sensitive L-type Ca2+ channels. . Entry of small amount of Ca from ECF 3. This Ca2+entry trigger the release of even more Ca2+from the SR (Ca2+-induced Ca2+release) through ryanodine sensitive Ca2+ release channels. Release of large amount of Ca from endoplasmic reticulum causes (calcium sparks) The amount of Ca2+released from the SR depends on the amount of Ca2+previously stored and on the size of the inward Ca2+current during the plateau of the action potential. In this way, a small amount Ca2+ entering the cytosol from the ECF induces a much larger release of Ca2+ into the cytosol from the intracellular stores. Duration of Contraction. Cardiac muscle begins to contract a few milliseconds after the action potential begins and continues to contract until a few milliseconds after the action potential ends. Therefore, the duration of contraction of cardiac muscle is mainly a function of the duration of the action potential, including the plateau— about 0.2 second in atrial muscle and 0.3 second in ventricular muscle. The extra supply of Ca2+ from the sarcoplasmic reticulum is responsible for the long period of cardiac contraction, which lasts about three times longer than a single contraction of a skeletal muscle fiber (300 msec compared to 100 msec). This increased contractile time ensures adequate time to eject the blood. 4. As a result of this Ca2+release, intracellular [Ca 2+] increases. 5. Ca2+ binds to troponin C, and tropomyosin is moved out of the way, removing the inhibition of actin and myosin binding. 6. Actin and myosin bind, the thick and thin filaments slide past each other, and the myocardial cell contracts (same steps as the skeletal muscles). The magnitude of the tension that develops is proportional to the intracellular [Ca2+]. Without the calcium from the T tubules, the strength of cardiac muscle contraction would be reduced considerably because the sarcoplasmic reticulum of cardiac muscle is less well developed than that of skeletal muscle does not store enough calcium to provide full contraction. The T tubules of cardiac muscle, however, have a diameter five times as great as that of the skeletal muscle tubules, which means a volume 25 times as great inside the T tubules is a large quantity of mucopolysaccharides that are electro-negatively charged and bind an abundant store of calcium ions, keeping them available for diffusion to the interior of the cardiac muscle fiber when a T tubule action potential appears. The strength of contraction of cardiac muscle depends to a great extent on the concentration of calcium ions in the extracellular fluids. In fact, a heart placed in a calcium-free solution will quickly stop beating. The reason for this response is that the openings of the T tubules pass directly through the cardiac muscle cell membrane into the extracellular spaces surrounding the cells, allowing the same extracellular fluid that is in the cardiac muscle interstitium to percolate through the T tubules. Consequently, the quantity of calcium ions in the T tubule system (i.e., the availability of calcium ions to cause cardiac muscle contraction) depends to a great extent on the extracellular fluid calcium ion concentration. In contrast, the strength of skeletal muscle contraction is hardly affected by moderate changes in extracellular fluid calcium concentration because skeletal muscle contraction is caused almost entirely by calcium ions released from the sarcoplasmic reticulum inside the skeletal muscle fiber. 7. Relaxation occurs when: A. Ca2+ is re-accumulated by the SR by an active Ca2+ATPase pump. B. Ca2+ is released to outside the cell in two steps. First step: Na-Ca exchanger; to exchange Calcium with Na inside the cell Second step: Na-K ATPase; to exchange entered Na with K. The spread of cardiac excitation is coordinated to ensure efficient pumping: Once initiated in the SA node, an action potential spreads throughout the rest of the heart. For efficient cardiac function, the spread of excitation should satisfy three criteria: 1) Atrial excitation and contraction should be complete before the onset of ventricular contraction 2) Excitation of cardiac muscle fibers must be coordinated to ensure a smooth, uniform ventricular contraction essential to squeeze out the blood. Random, uncoordinated excitation and contraction of the cardiac cells is known as fibrillation. 3) The pair of atria and pair of ventricles should be functionally coordinated so that members of the pair contract simultaneously Mechanical events of the heart: The de-polarization process triggers a wave of contraction that spread through the myocardium. The cardiac cycle is the performance of the human heart from the beginning of one heartbeat to the beginning of the next. The cardiac cycle consists of two periods: a period of relaxation called "diastole", during which the heart fills with blood, followed by period of contraction called "systole". The (systolic pressure) refers to the peak pressure reached during systole. The (diastolic pressure) refers to the lowest pressure during diastole. Ventricular diastole (0.5 sec) Ventricular diastole is the period during the cardiac cycle between aortic valve closure → mitral valve open → mitral valve closure. Ventricular diastolic volume between end-systolic volume to end-diastolic volume Ventricular diastolic divided into a. isovolumic relaxation (from aortic valve close to mitral valve open) (0.1 sec) b. Ventricular filling (rapid filling or inflow phase (0.1sec), slow filling phase (0.2 sec), and atrial systole(0.1sec)) from mitral valve open to mitral valve close. Ventricular systole (0.3sec) Ventricular systole is the period during the cardiac cycle between mitral valve closure→ aortic valve open → aortic valve closure. Ventricular systolic volume between end-diastolic volume to end-systolic volume Ventricular systole divided into a. isovolumetric contraction (from mitral valve close to aortic valve open (0.05 sec but 0.015 sec for right ventricle) b. ventricular ejection (Maximal (or rapid) ejection (0.1 sec) and reduced ejection (0.15 sec) Pressure-volume loop (Wiggers diagram): It is possible to record changes in ventricular pressure and volume during cardiac cycle. These records result in a loop (pressure-volume loop) passes into: Phase one (Ventricular filling) We are going to discuss the left side of the heart (the same event occurs with same sequences in the right side of the heart) It begins from mitral valve opening and end at mitral valve close. It begins with end-systolic volume and ends at end-diastolic volume. Ventricular filling passes into three stages: a. rapid filling of the ventricles: During ventricular systole, large amounts of blood accumulate in the right and left atria because of the closed mitral valves. Therefore, as soon as systole is over and the ventricular pressures fall again to their low diastolic values, the moderately increased pressures that have developed in the atria during ventricular systole blood immediately push on the mitral valves and open it so allow blood to flow rapidly into the ventricle. In normal individuals, this phase accounts for the majority of ventricular filling. This phase is characterized by the descent on atrial pressure tracings and then equally rapid rise in ventricular pressure. As the rate of ventricular filling declines, the slow filling phase is entered, following by diastasis (a period when ventricular filling ceases). b. slow filling or reduce ventricular filling: the atrial and ventricular pressures are similar and continued filling of the ventricles is dependent on blood returning from the peripheral circulation that continues to empty into the atria from the veins and passes through the atria directly into the ventricles. Only a small amount of blood normally flows into the ventricle, but the slow filling period lasts longer than the rapid filling period in the normal heart. c. atrial systole “atrial kick”: Atrial systole the last phase of ventricular diastole. Atrial systole is the contracting of cardiac muscle cells of both atria following electrical stimulation and blood is pumped into the ventricles through the open atrioventricular valves. Atrial systole actually performs the vital role of completing the ventricular diastole, which is to finalize the filling of both ventricles with blood while they are relaxed and expanded for that purpose. The atrial kick closes the diastole immediately before the heart again begins contracting and ejecting blood from the ventricles (ventricular systole) to the aorta and arteries. Steps in excitation-contraction coupling The term “excitation-contraction coupling” refers to the mechanism by which the action potential causes the myofibrils of muscle to contract (with some similarity between skeletal and cardiac muscles) 1. The action potential spreads from the cell membrane into the T tubules. 2. During the plateau of the action potential, Ca2+conductance is increased and Ca2+ enters the cell from the extra-cellular fluid (inward Ca2+current) through di-hydro-pyridine sensitive L-type Ca2+ channels. . Entry of small amount of Ca from ECF 3. This Ca2+entry trigger the release of even more Ca2+from the SR (Ca2+-induced Ca2+release) through ryanodine sensitive Ca2+ release channels. Release of large amount of Ca from endoplasmic reticulum causes (calcium sparks) The amount of Ca2+released from the SR depends on the amount of Ca2+previously stored and on the size of the inward Ca2+current during the plateau of the action potential. In this way, a small amount Ca2+ entering the cytosol from the ECF induces a much larger release of Ca2+ into the cytosol from the intracellular stores. Atrial kick is absent or disrupted. a. if there is loss of normal electrical conduction in the heart, such as caused by atrial fibrillation and flutter, heart block. b. "stiff heart" found in patients with diastolic dysfunction. Atrial systole represented by the P wave of the ECG. Atrial systole usually causes 20-30 percent filling of the ventricles while 70–80 percent is due to inflow during atrial diastole. However, the heart can continue to operate under most conditions even without this extra 20-30 percent effectiveness because it normally has the capability of pumping 300 to 400 percent more blood than is required by the resting body. Therefore, when the atria fail to function, the difference is unlikely to be noticed unless a person exercises; then acute signs of heart failure occasionally develop, especially shortness of breath. Ventricular filling phase in the volume-pressure diagram begins at a ventricular volume of about 45 milliliters and a diastolic pressure near 0 mm Hg. Forty-five milliliter is the amount of blood that remains in the ventricle after the previous heartbeat and is called the end-systolic volume. As venous blood flows into the ventricle from the left atrium, the ventricular volume normally increases to about 115 milliliters, called the end-diastolic volume, an increase of 70 milliliters and the diastolic pressure rising to about 5 mmHg. Phase two (iso-volumetric contraction or isovolumic or isometeric ventricular contraction ) Mechanically, the isovolumic phase of ventricular systole is defined as the interval between the closing of the mitral valves and the opening of aortic valves. Isovolumetric begins at the end of ventricular diastole Isovolumetric marks the beginning of systole Ventricular muscle initially shortens relatively little, but because the mitral valve will be closed preventing blood to return to atria and aortic valve is still closed because ventricular pressure did not reach the pressure that can open it so no blood will pass out of ventricle causing intra-ventricular pressure rises sharply and continue to rise till it reaches pressure that can open aortic valve (80 mmHg). During iso-volumetric contraction, a. the mitral vales bulge into the atria, causing a small but sharp rise in atrial pressure. b. corresponds to the R peak or the QRS complex seen on an ECG. Phase three (ventricular ejection) a. Rapid ejection: from 80mmHg diastolic pressure to 120mmHg systolic pressure Rapid ejection represents initial, rapid ejection of blood into the aorta from the left ventricles. Rapid ejection begins when the intraventricular pressures exceed the pressures within the aorta by a few mmHg, which causes the aortic valves to open (slightly above 80mmHg) and then eject blood to aorta as it reaches slightly above 120mmHg). Blood is ejected because the total energy of the blood within the ventricle exceeds the total energy of blood within the aorta. In other words, there is an energy gradient to propel blood into the aorta from the left ventricles. Maximal outflow velocity is reached early in the ejection phase, and maximal (systolic) aortic pressures are achieved. No heart sounds are ordinarily noted during ejection because the opening of healthy valves is silent. The presence of sounds during ejection (i.e., systolic murmurs) indicate aortic stenosis or intracardiac shunt. Left atrial pressure initially decreases as the atrial base is pulled downward, expanding the atrial chamber. Blood continues to flow into the atria from their respective venous inflow tracts and the atrial pressures begin to rise. This rise in pressure continues until the mitral valves open at the end of isovolumetric relaxation. b. Reduced (or slow) ejection: from 120 systolic pressure to 100 end systolic pressure This phase marks the beginning of ventricular repolarization as depicted by the onset of the T wave on the ECG. Repolarization leads to a rapid decline in ventricular pressures (reduce from 120mmHg to 100mmHg) and hence the reduced rate of ejection. However, some forward flow of blood continues secondary to remnant kinetic energy from the previous phase. Approximately 60 percent of the blood (70 mL out of 115 mL) in the ventricle at the end of diastole is ejected during systole (EDV-ESV); about 70 percent of this portion flows out during the first third of the ejection period, with the remaining 30 percent emptying during the next two thirds. When the pressure inside the ventricle reaches 80mmHg the blood ejection stops, and the blood try to return to ventral this cause the closure of aortic valve producing the second heart sound. This closed will ends the ejection phase (systolic phase) and begin of diastolic phase. Phase four (isovolumetric relaxation): After the aortic and pulmonary valves are closed, pressure continues to drop rapidly even though the ventricular volume does not change, giving rise to the period of isovolumic or isometric relaxation. Iso-volumetric relaxation ends when the ventricular pressure falls below the atrial pressure and the AV valves open, permitting the ventricle to fill to begin a new cycle of ventricular pumping. Thus, the ventricle returns to its starting point, with about 45 milliliters of blood left in the ventricle and at an atrial pressure near 0 mmHg. The volume of blood that remains in a ventricle is called the end-systolic volume and is ~45 ml in the left ventricle. The difference between the end-diastolic volume and the end-systolic volume is ~70 ml and represents the stroke volume. Left atrial pressure continues to rise because of venous return from the lungs. The peak Left atrial pressure at the end of this phase is termed the v-wave. Prolonged Iso-volumetric relaxation time indicates poor myocardial relaxation. Timing of events in the right and left sides of the heart: Although events on the two sides of the heart are similar, they are somewhat asynchronous‫غير متزامنة‬. Right atrial systole precedes‫ يسبق‬left atrial systole. Contraction of the right ventricle starts after that of the left ventricle. Science pulmonary arterial pressure is lower than aortic pressure; right ventricular ejection begins before left ventricular ejection. During expiration, the pulmonary and aortic valves close at the same time; but during inspiration, the aortic valves closes slightly before the pulmonary. The slower closure of the pulmonary valves is due to lower impedance of the pulmonary vascular tree. When measured over a period of minutes, the outputs of the two ventricles are, of course, equal, but transient differences in output during the respiratory cycle occur in normal individuals. The volume of ejected blood: Stroke volume Stroke volume: is the volume ejected from the ventricle on each beat. Stroke volume is expressed by the following equation: Stroke volume = (End-diastolic volume) – (End-systolic volume) End-diastolic volume; is the volume of the ventricle before ejection. End-systolic volume; is the volume of the ventricle after ejection. Left ventricular stroke volume = Right ventricular stroke volume. Cardiac output Cardiac output: is amount of blood ejected per minute. Cardiac output is expressed by the following equation: Cardiac output = Stroke volume x Heart rate Left ventricular Cardiac output = Right ventricular Cardiac output Young, healthy men, resting cardiac output averages about 5.6 L/min. Young, healthy women, resting cardiac output averages about 4.9 L/min. The following factors, among others, directly affect cardiac output: Ejection fraction is most commonly measured using echocardiography. During exercise in highly conditioned individuals, the increased stroke volume can result in the Ejection fraction exceeding 90%. In heart failure, Ejection fraction can become very small as Stroke Volume decreases and end-diastolic ventricular volume increases. In severe heart failure, EF may be 20% or less. There are circumstances in which Ejection fraction can be normal, yet the ventricle is in failure. One example is diastolic dysfunction caused by hypertrophy and restrictive cardiomyopathy in which filling is impaired because of low ventricular compliance (i.e., "stiff" ventricle: Physically, compliance (C) is defined as the change in volume (ΔV) divided by the change in pressure (ΔP)) and stroke volume is therefore reduced. In this case, both Stroke volume and End diastolic volume can be reduced such that Ejection fraction does not change appreciably. For this reason, low ejection fractions are generally associated with systolic dysfunction rather than diastolic dysfunction. In a disease state such as dilated cardiomyopathy, the ventricle becomes very dilated without appreciable thickening of the wall. This dilated ventricle will have increased compliance; therefore, although the End diastolic volume may be very high, the End diastolic pressure may not be greatly elevated. Cardiac index (CI) Cardiac index=Cardiac output (L/min) ÷ Body surface area (m2) The normal range of cardiac index in rest is 2.6–4.2 L/min/m2. The cardiac index rises rapidly to a level greater than 4 L/min/m2 at age 10 years and declines to about 2.4 L/min/m2 at age 80 years. Autonomic Supply to Cardiovascular system: Parasympathetic nerve (Vagus): The SA node, atria, and AV node have parasympathetic vagal innervations, but the ventricles do not. The neurotransmitter is acetylcholine (ACh), which acts at M2 muscarinic receptors. Could act directly or indirectly through inhibition of sympathetic system. The right vagus is distributed mainly to the SA node and left vagus mainly to the AV node. Sympathetic nerve Heart: The SA node, AV node, conducting system, atria, and ventricles. The sympathetic innervation on the right side is distributed primarily to the SA node and the sympathetic innervations on the left side primarily to the AV node. The heart has both beta1 (β1) and beta2 (β2) adrenoceptors, although the predominant receptor type in number and function is β1 but β2-adrenoceptors become functionally more important in heart failure because β1-adrenoceptors become down regulated. β1 and β2 adrenoceptor bind: a. norepinephrine that is released from sympathetic adrenergic nerves. b. norepinephrine and epinephrine that circulate in the blood. β1 and β2 adrenoceptor both have similar cardiac effects when stimulated β1 and β2 adrenoceptor activation of these receptors increases: a. heart rate and contractility→↑ cardiac output. b. conduction velocity within the heart c. rate of mechanical relaxation (lusitropy). Nor-epinephrine can also bind to α1-adrenoceptors found on myocytes to produce small increases in inotropy. Noradrenergic fibers are epicardial, whereas the vagal fibers are endocardial. Acetylcholine acts pre-synaptically to reduce nor-epinephrine release from the sympathetic nerve, and conversely, neuro-peptide Y released from nor-adrenergic ending may inhibit the release of acetylcholine.