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Outline the effects of the sympathetic nerves on the heart? Sympathetic nerves act as part of the reaction to the ‘fight, fright or flight’ scenario. The nerves are distributed not only to the sinoatrial and atrioventricular nodes but also to the cardiac muscle of both ventricles and atria. The effects of sympathetic innervation can be broken down into increasing the heart’s rate of pumping and also increasing the heart’s strength of contraction. The sympathetic nerves release noradrenaline at their junctions. Sympathetic activity also causes adrenaline to be released from the adrenal medulla. Both these neurotransmitters bind to β 1 adrenoreceptors in the SA node. This process increases cAMP levels in the cell and results in a faster increase in sodium and calcium permeability during the pacemaker stage of the potential and thus producing early action potentials. Hence more action potentials can occur in a set time and the rate of firing of the SA node determines the rate of contraction in the heart and so this increases as well. Sympathetic fibers also innervate the atria, AV node, Purkinje fibers and ventricular muscle. Their effect here is mostly to increase the speed of conduction. The AV node delay is decreased and the action potential duration itself is shortened. This shorter cycle is caused by sarcolemmal increases in permeability to potassium and calcium ions and a more rapid uptake of calcium ions in to the sarcoplasmic reticulum. The other effect of the sympathetic innervation in increasing contractile strength and ejection velocity is explained by the increased permeability to calcium ions which are essential for the contraction process. In this way cardiac output can be increased by up to 100%. Under normal conditions the sympathetic stimulation has the heart pumping at about 30% of a higher rate than it would do without stimulation. Explain the effects of parasympathetic nerve activity on heart rate. The parasympathetic nerve system is associated with energy conservation and the normal activity of the body. Parasympathetic activity decreases the heart rate. Both sympathetic and parasympathetic systems are tonically active in the heart but the latter is more active in humans at rest and reduces the rate from about 100 to 70 beats per minute. Since the vagus transmits the parasympathetic fibers, the heart is described as having vagotonic tone. The vagus has fibers distributed to the AV and SA nodes as well as the atria. The system releases acetylcholine at its junctions and this acts on muscarinic cholinoceptors in the SA node to hyperpolarize and slow the rate of pacemaker potential depolarization. The hyperpolarization is achieved by a decrease in cAMP activity which is triggered by the muscarinic receptors which inhibit adenylate cyclase via the G protein. This decrease in cAMP causes additional potassium channels to open, and reductions in the permeability to calcium and sodium ions reduces the slope of the pacemaker potential. This response is faster to occur than sympathetic stimulation. Parasympathetic fibers also innervate the atria and the AV node where it increases the AV node delay. The action potential duration itself is lengthened by parasympathetic activity. Although parasympathetic innervation via the muscarinic receptors decreases atrial contractility it does not affect ventricular contractility. This reinforces the notion that the main effect of parasympathetic innervation is to reduce heart rate and hence cardiac output. Discuss the mechanisms used by the body to increase cardiac output. Cardiac output is the volume of blood pumped per minute by each ventricle. It is the product of stroke volume and heart rate. Thus to increase the cardiac output, one must increase either of these two elements. To increase, heart rate, sympathetic stimulation can increase the rate of firing in the SA node and also the rate of conduction of action potentials in the heart’s conducting system and this increases the heart rate. On the other hand, stroke volume is subject to intrinsic and extrinsic control. Intrinsic control causes the heart to respond with a greater force of contraction, ejecting a larger stroke volume when end diastolic volume increases according to Starling’s law of the heart. EDV can be altered by events in the chest and changes in blood volume or venous capacity. More negative intrathoracic pressure than normal such as occurs on large inspirations will increase EDV. An increased venous return when one changes from standing to reclining will do the same. A moderate increase in heart rate increases end-diastolic volume due to an increase in atrial contractility. Very high heart rates are more complicated. A very high heart rate reduces the time available for filling and so end diastolic volume has a tendency to fall. The increase in myocardial contractility increases the rate of ventricular relaxation and this increases the rapid phase of ventricular filling. On balance the end diastolic volume remains about the same and so cardiac output increases. Increased volumes in the ventricle produce stronger contractions as the cardiac muscle fibers are normally at a less than optimal state before contractions. Increased volumes bring the fibers closer to the optimal position and thus contractile strength increases. This control is limited as the ventricle can only stretch to a limit before one exceeds the optimal position. Extrinsic control is dependent on sympathetic controlled calcium entry into muscle fibers which enhances myocardial contractility and ejection velocity. Draw an ECG trace and briefly explain the origin of each wave. The first wave in an ECG is the P wave. This is caused by atrial depolarization. The SA node produces action potentials which spread throughout the atrial muscle which then depolarizes as a synctium. The action potential causes the opening of fast sodium channels and slower calcium channels with a decrease in permeability to potassium ions which depolarizes the membrane. The inside of the cell thus becomes positive and the outside is also reversed to become negative. The P wave is soon followed by atrial contraction. The next wave is the QRS complex. This is the product of depolarization of the ventricles. The complex hides the repolarization of the atrium which happens almost simultaneously. Thus while the atria are relaxing the ventricles start to contract. The Q and S parts are negative because their vectors are directed to the right. The S wave is directed upwards and to the right because the last part of the myocardium to be depolarized is the base. The T wave then corresponds to the ventricular repolarization due to the action of slow acting potassium channels which leak potassium ions out of the cell and cause it to repolarize. The PQ interval is the time taken for excitation to spread through the atria, AV node and bundle of His. The QT and PS intervals are measurements of the duration of ventricular and atrial action potentials. The reason for the dip before the spike in the QRS complex is because as ventricular depolarization begins at the IV septum which depolarizes from left to right, it gives a vector directed downwards to the right. How do myocardial autorhythmic cells generate spontaneous depolarizations? The resting membrane potential of the cells of the SA node is between -55 to -60 mV which is less than normal. The lower negativity is caused by the leaky nature of the membrane of there cells which allow sodium and calcium ions to enter and thus reduce the negativity of the cell interior. Although most of the fast sodium channels are closed, the leaky membrane and the high sodium concentration outside the cell causes further sodium entry and when the membrane depolarizes to about -40mV, the sodium-calcium channels open. Thus the depolarization process quickens up until potassium channels open and cause repolarization as positive potassium ions leave the cell. At the same time as the opening of the potassium channels the sodiumcalcium channels close. Thus a state of hyperpolarization is obtained but the potassium channels gradually close and the leaky membrane lets the sodium and calcium ions in again until the threshold is again reached and another action potential is released. The rate of action potentials in the SA node is higher than in the other autorythmic cells and so it is referred to as the pacemaker of the heart. Explain how heart sounds are generated during a cardiac cycle. Heart sounds are caused by the closure of valves in the heart. The first heart sounds are caused by the closure of the AV valves, the bicuspid or mitral and tricuspid valves respectively. These are opened by the pressure building in the atria as they fill with blood to allow filling of the ventricle. When the ventricle is filled, however, the ventricular muscle begins to contract and an effect of the rising pressure in the ventricle is the closure of the AV valves. This produces the first heart sound. After this blood is ejected through a second set of valves, the semilunar valves of the pulmonary trunk and aorta. However when the blood is ejected, the pressure in the ventricle begins to fall rapidly as the muscle relaxes. For a moment, the pressure in the aorta and pulmonary trunk is higher than that in the respective ventricle and thus a reflux of blood occurs in the direction of the heart. This causes the semilunar valves to collect the blood into their sinuses and they close. This causes the second heart sound, which is shorter due to the more rapid closure. Describe the responses of the cardiovascular and respiratory systems to exercise. What property of the sino-atrial node makes it the normal pacemaker of the heart? The slope of the pacemaker potential in the SA node is steeper than in the AV node. Therefore the SA node triggers its action potential first and is the pacemaker from which the heart beat originates. The action potential arrives in the AV node well before the pacemaker in the AV node has reached its threshold and thus is triggered to activation by the AV’s rate of pulsation. With the aid of a diagram, clearly indicate the pressure changes that occur in the right side of the heart during a cardiac cycle. The right atrium has a negative pressure at the end of its ejection of slightly below zero. This allows a pressure difference for venous blood return from the capillaries and veins which drain the tissues. It rises to about 2mmHg due to blood from the veins accumulating behind a closed AV valve. This is signified by the v wave on the diagram. When right ventricular pressure drops to below this, the AV valve opens and the blood enters the ventricle. This corresponds to the y descent in the graph. Atrial contraction in response to depolarization occurs in late diastole and this contributes the final 20% to ventricular filling. This is signified by the a wave in the graph. Soon after this the ventricle starts to contract. When it reaches a greater pressure than the right atrium, the tricuspid valve is forced to close. The bulging of the AV valve back into the atrium causes its pressure to rise to about 5mmHg, known as the c wave. Then, after the isovolumetric contraction period, when ventricular pressure exceeds pulmonary pressure the pulmonary valve opens and blood is ejected. The pressure recorded in the pulmonary trunk is 8mmHg in diastole and 25mmHg in systole. The AV fibrous rings are pulled down during this ejection and this leads to the x descent in the atria. The ventricles soon relax again and pressure drops leading to the closure of the pulmonary valve and the opening of the AV valve again. Explain the changes that occur in each of the following when sympathetic nerves to the heart are activated: (a) R-R interval This refers to the time taken for one full cycle in the ECG to occur. The interval is reduced as the rate of firing in the SA node increases due to noradrenaline activating a cAMP second messenger system in the cells which increases the cells permeability of sodium and calcium ions. Thus a higher firing rate increases the number of ECGs recorded in a set time. The length of the ECGs themselves also decreases due to the increased conduction speeds and shorter action potentials in the electrical conduction system of the heart, in the AV node and purkinje fibers etc. Thus the interval between two R waves is reduced by both these effects. (b) P-R interval This refers to the time taken for depolarization to spread from the atria to the ventricles. This time is shortened because the conduction speeds of the atria and the AV nodes as well as the purkinje fibers and the ventricles are all increased under the influence of sympathetic innervation. The action potential time itself and the AV node delay are both reduced and so the time between atrial and ventricular depolarizations is reduced. (c) duration of systole Systole refers to the contraction of the ventricles and their emptying of blood into the aorta and pulmonary vessels. The length of contraction is dependent on the time between ventricular depolarization and repolarization. This time interval would decrease because of the increased permeability to potassium and calcium in the sarcolemma. Outline the changes that occur in the cardiovascular system when one changes from a supine to an upright position. When this change occurs, the blood pools in the legs and so venous return is reduced to the heart. Venous return determines end diastolic volume and this in turn determines stroke volume. Hence if blood pools in the legs, cardiac output via stroke volume is reduced. Discuss the factors that can aid venous return to the heart. Firstly, 70% of the body’s blood is beneath the level of the heart when standing. Thus the blood must flow uphill to reach the heart from the veins. One way of increasing the venous return to the heart is to lie down. In a supine position blood can flow readily and does not have to oppose the force of gravity. Another factor is the work of the muscle pump which pushes blood through the veins when the muscles around them contract. This muscle pump thus increases in activity when a person is moving for example when walking the leg muscles contract and cause blood to flow more rapidly towards the thorax. This muscle pump when active increases the venous return to the heart. Obviously to avoid the reflux of blood back down to the feet after its movement towards the thorax, valves are an essential factor. Although they do not actively increase venous return through activation or inactivation, the venous return of some one whose valves are incompetent will be a lot less than some one whose valves are functional. The respiratory pump is also a factor. Flow in the venae cavae increases during inspiration and falls on expiration. This effect is enhanced when someone breathes deeply. The intrathoracic pressure is as low as -5mmHg at the end of respiration and this causes dilation of intrathoracic veins during inspiration. The descent of the diaphragm increases abdominal pressure and compresses its veins. The decreased resistance to flow towards the thorax thus can increase venous return. There is also a suction effect of the heart’s right atrium found during the x and y descents. These occur when the AV ring moves downwards and the AV valve opens respectively. Both these events, temporarily increase venous return and this effect is greatest during greater cardiac activity. The primary factor which regulates the venous return is the right atrial filling pressure. This is the pressure difference between the mean right atrial pressure and the mean systemic filling pressure. MSFP is usually about 7mmHg and is otherwise known as circulatory pressure. MSFP increases when blood volume is expanded (when venous capacity is decreased). Thus when the venous blood is compressed by venoconstriction, the MSFP rises. Mean right atrial pressure is about 1mmHg and so the difference determines the rate of venous flow into the heart. Describe the reflex responses that occur when blood pressure is elevated above normal levels. Baroreceptors are located in the wall of the aortic arch and also in the carotid sinus. An increase in transmural pressure stretches the arterial wall and stimulates the baroreceptors. This causes the frequency of their action potentials to increase and the recruitment of more afferent fibers. An increase in arterial pressure will cause the following changesThere is an increase in parasympathetic and a decrease in sympathetic discharge to the SA node causing a fall in heart rate. There is a decrease in sympathetic discharge to ventricular muscle and the subsequent decrease in contractility means a reduction in stroke volume. There is a decrease in sympathetic discharge to the veins which causes increased compliance and capacity, reducing end diastolic volume. There is a decrease in sympathetic discharge to the arterioles causing a decrease in total peripheral pressure. This will result in a greater capillary pressure, more ultrafiltration across the capillary wall and thus a reduction in blood volume. Draw a diagram which shows clearly the magnitude and time course of a ventricular action potential. Show diagrammatically the conductance changes which are responsible for this potential change. The action potential in the ventricles has a magnitude of about 110 mV. The resting membrane potential is about -90mV and this rises as high as +20mV. After the initial spike, the membrane remains depolarized for about 0.2 seconds which gives ventricular muscle a contraction 15 times longer than skeletal muscle. Then about 0.3 seconds into the action potential the membrane becomes repolarized and the action potential ends. The above diagram shows the conductance changes in the membrane of a ventricular muscle fiber during an action potential. The yellow line shows the opening of the fast acting sodium channels which causes a spike in the action potential and a dramatic depolarization once the membrane potential reaches threshold. The red line then shows the increase in permeability to calcium ions, the opening of the so called slow calcium channels. This is responsible for the plateau in the action potential. Finally in blue is the conductance change for potassium ions which is originally reduced by the membrane depolarization but slowly the effects wear off and more potassium channels reopen and repolarize the membrane and lead to the fall in the action potential. Describe the effects on left ventricular stroke work of: (a) increased mean arterial pressure; (b) decreased venous return. (c) increased heart rate; Describe the role of the Purkinje system in the heart. The purkinje fiber system is a part of the conducting system of the heart which allows the spread of electrical excitation arising rhythmically from the SA node in the right atrium. The purkinje fibers travel from the AV node in the IV septum in two bundles of fibers towards the apex of the heart. They allow for fast conduction of the action potentials so that all parts of the ventricles contract at roughly the same time. Thus they are large fibers (the greater the diameter of the fiber the faster the velocity) which allow conduction speeds of up to 2-4m/s. This speed allow for almost instantaneous transmission of the excitation throughout the ventricles. The high speeds of conduction are accounted for also by the high level of permeability in the gap junctions between successive fibers. The fibers also have very few myofibrils which means little contraction during the course of the conduction of the impulse. A man has a heart rate of 40 beats/min. His ECG has no P waves but has normal QRS complexes. What is the likely explanation? This is a slow heart rate. It should be as high as 70 beats/min which is roughly the rate set by the SA node. The fact that the ECG has no p waves implies that there is no atrial depolarization. Both these facts lead to the conclusion that the SA node is not discharging at its normal pacemaker level and so an ectopic pacemaker, perhaps in the AV node is now controlling the heart rate. Use a diagram to show the immediate effects of a sudden, severe decrease in cardiac pumping ability on cardiac output and right atrial pressure. A sudden decrease in cardiac pumping ability would lead to a fall in stroke volume; that is the volume of blood pumped by the heart would decrease. As cardiac output is dependent on stroke volume by heart rate, then this would also fall. Mean arterial pressure would also be reduced due to the reduced blood output. The end diastolic volume in the heart before the next contraction would then greatly increase as would the atrial pressure as blood will accumulate here also. The graphical effect of this decrease in pumping ability can be seen on pg. 397 of lecture notes on human physiology. Account for the changes in each of the following when impulse frequency in baroreceptors nerves is increased: (a) heart rate; The impulse rate in the baroreceptor nerves controls the level of sympathetic and parasympathetic stimulation in the body. An increase in MABP will increase the impulse frequency of the baroreceptors. The reflex change is a decrease in sympathetic activity to the SA node and an increase in the parasympathetic innervation leading to bradycardia. This will reduce the cardiac output and thus the MABP. (b) venous tone; There is a decrease in sympathetic innervation of the veins. This leads to an increased venous compliance and capacity. The end diastolic volume of the heart is thus reduced as the relaxation of the veins reduces venous return and the end result of this is to reduce cardiac output via stroke volume. This will reduce the MABP. (c) splanchnic blood flow. The baroreceptor reflex decreases sympathetic activity to the arterioles and this leads to a decrease in the TPR. This vasodilation is greatest in the Splanchnic area. There is great potential for blood reservoir usage here and so diverting blood flow in this direction will lessen the amount of blood flow in the skeletal circulation etc. Thus sending blood more easily towards the Splanchnic area can reduce blood volume and hence lower MABP. Discuss the factors which determine blood flow through skeletal muscle . Skeletal muscle receives at rest about 20% of the cardiac output through a highly resistant vascular bed, the tone of which is controlled by sympathetic innervation and also by myogenic autoregulation. The veins in skeletal muscle are almost devoid of sympathetic nerve endings and so their venous capacity cannot be altered and they cannot act as a blood reservoir. During exercise, vasodilation occurs in skeletal blood flow. This vasodilation is mainly controlled by metabolites being released from the energy consuming muscle fibers. Decreases in pO2, increases in pCO2 pH, potassium ions, osmolality and adenosine all cause vasodilation. It is impossible to say which has the strongest effect as the removal of one metabolite leads to compensation from the others. The contraction of the muscle itself has the effect of compressing the blood vessels and reducing blood flow into the muscle. If the contraction is phasic, the blood flow is then seen to be intermittent and the compensation occurs during relaxations. In maintained contractions, the metabolites build up but the compression of the blood vessels is the governing factor. When contraction ends, the metabolites have an extremely powerful compensatory effect to replenish the oxygen debt. In skeletal muscle blood vessels, both α and β receptors are present, where activation of the former causes constriction and the latter causes dilation. Noradrenaline released from sympathetic fibers causes constriction and adrenaline, which is present in the circulatory system during exercise, causes vasodilation. When exercise is ongoing, strange sympathetic fibers are activated and these release acetylcholine at the nerve endings. The acetylcholine leads to vasodilation which is paradoxical as one would expect it to cause smooth muscle to contract. It acts on endothelial cells to synthesize nitric oxide which diffuses out of the cell and causes smooth muscle relaxation. Another effect of exercise is to open more muscle capillaries to allow for greater blood flow through the tissue. Discuss the factors that determine blood flow through: (a) brain (see cerebral blood flow) (b) skin Cutaneous circulation has two main functions. It provides nutrition to the tissues and supports metabolic activity and also acts to transfer heat from the core of the body to the surface. There is a high level of tonic sympathetic activity in the skin. These release noradrenaline which causes constriction of the blood vessels and reduces blood flow. This is an important regulatory step in defense against hemorrhage. Cutaneous tissue can tolerate low blood flow levels by reducing its oxygen consumption proportionately. Metabolic regulation is thus deemed to be poor unless the blood flow has been reduced for some time in which case reactive hyperemia can occur. Large numbers of arteriovenous anastomoses can also occur in the skin. These have smooth muscle walls which remain contracted under sympathetic stimulation. When body temperature increases, the sympathetic levels decrease and these pathways open. No exchange of nutrients occurs along these anastomoses but heat is dissipated in the skin surface. Metabolic regulation can over-ride sympathetic control when the body is exposed to the cold to cause vasodilation. A triple response is also described to when pressure is applied to the skin from the outside. Firstly the area of contact is seen to go pale, the mechanical pressure initiating local contraction of venules or precapillary sphincters. Greater pressure then causes the skin to become red, followed by a flare and then a local swelling. This is the triple response. The red reaction probably results form damaged cells releasing histamine which is a potent vasodilator. The flare results form mechanical stimulation of nocireceptors which release substance P (dilating local arterioles and causing mast cells to release more histamine) and the wheal results from the increase in capillary permeability induced by histamine and substance P with a consequent rise in interstitial fluid. Finally adrenaline as is released from the adrenal medulla due to sympathetic stimulation also causes intense vasoconstriction. This explains why people go white when they get a fright. Explain why contractions in cardiac muscle cannot sum or exhibit tetanus. This principle is explained with the refractory period of the heart in mind. During the absolute refractory period of the action potential the cardiac cell is inexcitable and during the further relative refractory period the heart gradually recovers excitability. A second action potential cannot be elicited during the ARP but a very strong stimulus can cause an action potential in the RRP. This is caused by the closure of the inactivation gates of the sodium channels shortly after the action potential opens the activation gates. These channels require the membrane to undergo repolarization before they will revert to their original conformation and then they can be reopened. The mechanical and electrical events of the cardiac muscle overlap quite an amount in time. All of the contraction has taken place by the time the absolute refractory period is over and cardiac muscle has begun to relax, which it continues to do so during the relative refractory period. Thus high frequency stimulation which is necessary to cause summation and tetanus in skeletal muscle is impossible in cardiac muscle where the action potential is much longer.