CARDIOVASCULAR PHYSIOLOGY (Gloria Marie M. Valerio, MD) Outline: 1. 2. 3. 4. 5. 6. 7. 8.Functional Anatomy of the Heart Properties of the Myocardial Cells Electrical Events Cardiodynamics Characterics, Properties, Functions of the Different Types of Blood Vessels Hemodynamics Microcirculation Mechanisms that Regulate Cardiovascular Function the different organs of the body. This is made possible by the pumping action of the heart, so when the heart contracts, it will pump blood to the arteries. The arteries in turn will distribute blood at a high pressure to the different organs of the body. And from the different organs of the body, blood then will be collected by the veins and returned to the heart. So the arteries are distributing blood vessels while the veins are collecting blood vessels. The capillaries will allow the exchange of fluid and solutes between intravascular and interstitial fluid compartments. The human heart is divided into two pumps: right and left and they are connected in series. The left heart pumps blood to the systemic or peripheral circulation by way of the aorta. The right heart pumps blood to the pulmonary circulation by way of the pulmonary artery. Systemic or peripheral circulation includes blood flow to all organ systems of the body except for the lungs. When the cells of the systemic or peripheral circulation are metabolizing, they consume oxygen and produce carbon dioxide that will now be collected by the veins and will have a low oxygen tension and a high carbon dioxide tension called unoxygenated/deoxygenated/venous blood . This blood will be emptied by way of vena cava to the right side of the heart. When the right heart contracts, this same blood will be ejected to the pulmonary circulation by way of pulmonary artery. Unlike the other arteries of the body, the pulmonary artery carries deoxygenated or venous blood. This same blood will then reach the pulmonary capillaries and this is where exchange of gases will take place between the alveoli in the lungs and blood in pulmonary capillary across respiratory membrane. The blood from the pulmonary capillaries will come from the right side of the heart – low oxygen tension, high carbon dioxide tension. The opposite is true with regards to air in alveoli - increase oxygen tension, low carbon dioxide tension. Movement or transport of these gases across the respiratory membrane is a passive process. It occurs by simple diffusion brought about by pressure gradient. So the transport of movement of oxygen will take place from alveoli to pulmonary capillary, the carbon dioxide goes in opposite direction. So the blood that will enter the Alveoli Increase pO2 Decrease pCO2 Decrease pO2 Increase pCO2 Pulmonary capillary Functional Anatomy of the Heart The normal position of the heart inside the thoracic cavity is slightly tilted to the left, pointing downwards. When the heart contracts, it has a wringing action, meaning to say, when the heart contracts, it rotates slightly to the right and that will now expose the cardiac apex, so that when you place the diaphragm of the stethoscope over the chest wall particularly on the fifth intercostal space, left mid-clavicular line, that is where you will heartbeat the loudest called apex beat or point of maximum impulse . Fifth intercostal space: Start palpating below the clavicle and first rib – the second intercostal space, and move three spaces down. The midclavicular line: left of the left clavicle, take note of the mid-point then move five spaces below. In males, it is easily located because it is exactly below the left nipple. In females, the location may be variable so you need to palpate. pulmonary vein is already oxygenated. Unlike the other veins in the body, the pulmonary vein carries oxygenated or arterial blood which will then be emptied on the left side of the heart which means the left heart pumps blood to the systemic circulation and receives blood from the pulmonary circulation while the right heart pumps blood to the pulmonary circulation and receives blood from the systemic circulation. The circulatory system is a closed system – whatever amount of blood will be pumped by the blood per minute will be equal to the volume of blood that will return to the heart per minute. Structures of the Human Heart PHOTO: Schematic diagram of the parallel and series arrangement of the vessels composing the circulatory system. The capillary beds are represented by thin lines connecting the arteries (on the right) with the veins (on the left). The crescent-shaped thickenings proximal to the capillary beds represent the arterioles (resistance vessels). The cardiovascular system consists of the heart at the center and the different blood vessels which are arranged in parallel and in series with each other. The red are the arteries, the blue are the veins, and the capillaries are the smallest vessels in the body. The major function of the cardiovascular system is to transport nutrients including oxygen to the different organs of the body and to remove the waste products of metabolism including carbon dioxide from 1 Shannen Kaye B. Apolinario, RMT The heart is divided into two pumps: the right and the left. The two pumps in turn are made up of two chambers: atrium and ventricle. The right heart is made up of the right atrium and right ventricle while the left heart is made up of the left atrium and left ventricle. The two atria are separated by a band of connective tissue forming the interatrial septum. The two ventricles are also separated by a band of connective tissue forming the interventricular septum. The two atria are separated from the two ventricles by a mass of connective tissue. The four chambers of the heart are separated by connective tissues. Other important structures in the heart are the valves and there are two sets of cardiac valves. Between the atria and ventricles are the atrioventricular valves - tricuspid valve on the right side and mitral valve on the left side. The tricuspid valve is between the right atrium and right ventricle while the mitral valve is between the left atrium and left ventricle. The other sets of cardiac valves are between the ventricles and the arteries – the pulmonary valve between the right ventricle and pulmonary artery; the aortic valve between the left ventricle and aorta. Functions of the valves: first, when they open, they allow blood to flow from one chamber of the heart to another – when the atrioventricular valves are open, blood flow from the atria to the ventricles and when the semilunar valves are open, blood ejects from the ventricles to the arteries. When they close, they will prevent regurgitation or backflow of blood. However, there are no cardiac valves between the atria and veins so when there is atrial contraction, small amount of blood backflows to the veins. There is only small amount of backflow because when the atria contracts, there is increase in pressure and the tendency is to push blood downwards to the ventricles and at the same time, when it contracts, the orifice of the veins becomes smaller. Structure of Cardiac Valves The wall of the atria and ventricles is made up of cardiac muscle. The atrial wall/musculature is thinner compared to the ventricular wall or musculature. The two atria functions as a primer pumps for the ventricles and as conduits of blood from veins to ventricles. It is therefore the ventricles with the thicker wall that are the major pumps in the heart with the left ventricular wall thicker than the right ventricular wall. The left ventricular wall is thicker because it pumps blood to the systemic circulation with an average pressure of 70-130 mmHg. On the other hand, the right ventricle will pump blood to the pulmonary circulation with an average pressure of only 4-25 mmHg. The left ventricle will have to pump blood against a higher pressure resistance in the systemic circulation compared to the right ventricle that will pump blood against a lower pressure in the pulmonary circulation. Since the opposing force is higher in the left ventricle, the tendency is to contract more forcefully because of increased workload resulting to hypertrophy of the muscle fibers. Although the left ventricular wall is thicker, contract more forcefully, higher workload and higher opposing force than the right, the output of the two ventricles is the same. Whatever amount will be ejected by the left ventricle per minute is the same with the amount of blood ejected by the right ventricle per minute. Aside from the cardiac muscles, the atrial and ventricular wall also contains a fair amount of elastic tissues that will enable the different chambers of the heart to dilate when the volume of the blood inside increases. Also present in the atrial and ventricular wall is a fair amount of connective tissue and this connective tissue in turn will prevent overstretching or distension of cardiac muscles when the cardiac size increases. PHOTO: Drawing of a heart split perpendicular to the interventricular septum to illustrate the anatomic leaflets of the atrioventricular and aortic valves. The three cardiac valves – tricuspid, pulmonary and aortic contains three cusps. It is only the mitral valve that contains only two cusps. For the atrioventricular valve, the cusps are attached by strong ligaments called chordae tendinae to the papillary muscle and the papillary muscle arises from the ventricular wall. Mitral valve has two cusps attached by the chordae tendinae to the papillary muscle. The semilunar valve – aortic valve has no chordae tendinae. Tricuspid valve has chordae tendinae attached to the papillary muscle and arises from the ventricular wall. Each cusp has an orifice or opening covered by leaflets which are made up of loose fibrous tissue. One end of the leaflets is attached to the border of the orifice while the central part is freely movable. Since it is thin and freely movable, it can open. However when they close, they close completely because there is extensive overlapping of the leaflets that cover the orifice of the cusp. Opening and closing of the cardiac valve is a passive process brought about by pressure differences between the two chambers of the heart. In the case of tricuspid valve for example, if the right atrium is contracting, the right ventricle is in a relaxed state. When the right atrium is contracting, the pressure increases and that will push open the tricuspid valve so that blood will flow from the right atrium and right ventricle. On the other hand, if it now the right ventricle contracting and the right atrium is relaxed, the high pressure in the right ventricle will close the tricuspid valve to prevent back flow of blood to the right atrium. It is also a passive process due to the pressure gradient. Same things happen with regards to the mitral valve as well as to the semilunar valves. When the ventricle is contracting, the papillary muscle also contracts but the contraction of the papillary muscle is not essential in closing the atrioventricular valves. Remember that when the ventricle is contracting due to the thick musculature, the pressure is high. So the high pressure will tend to push the AV valves to bulge into the atria PHOTO: Four cardiac valves as viewed from the base of the heart. Note how the leaflets overlap in the closed valves. 2 Shannen Kaye B. Apolinario, RMT however, when the papillary muscle contracts, it will pull the chordae tendinae to prevent eversion or over-bulging of the AV valves during ventricular contraction. the leaflets. In insufficient or incompetent cardiac valve, the leaflets do not close completely allowing back flow of the blood either from the ventricles to the atria or from the arteries to the ventricles. In normal mitral valve, when the left atrium is contracting, that is the amount of blood that will be ejected to the left ventricle. In stenotic mitral valve, even if the left atrium is contracting, there will be less amount of blood that will be ejected to the left ventricle. There will be now pooling of blood in the left atrium causing the left atrium to dilate. In stenotic aortic valve, the leaflets hardened so that during contraction, the amount of blood ejected in the aorta will be decreased. There will be pooling of blood in the left ventricle causing the left ventricle to dilate. An example of an insufficient or incompetent cardiac valve is a prolapsed mitral valve. When the left ventricles contract, it does not close even if there is blood ejected in the aorta, it will be lessened because of the backflow of blood in the left atrium. Presence of a stenotic or an incompetent cardiac valve will produce abnormal heart sounds called a murmur. PHOTO: Mitral and aortic valves (the left ventricular valves) Valve Mitral Aortic Heart Sounds Closing of the cardiac valves will produce the normal heart sounds. The first heart sound is at the onset of ventricular contraction with closing of AV valve. That closing of AV valve produces the first heart sound. Compared to the second heart sound, closing of the AV valve is said to be louder and longer in duration. The sound produced by the closing of the tricuspid valve is heard best on the fifth intercostal space, left of the sternum while the sound produced by closing of the mitral valve is heard best on the fifth intercostal space at the cardiac apex - left mid-clavicular line. The second heart sound occurs at the onset of ventricular relaxation with closing of the semilunar valves. And because of the pressure in the arterial system, when the semilunar valves close, they close abruptly and that will make the duration of the heart sound shorter. The sound produced by the closing of the pulmonary valve is heard best on the second intercostal space left of the sternum while the sound produced by the closing of the aortic valve is heard best on the second intercostal space right of the sternum. The quality of the second heart sound can be affected by respiratory phase – expiration and inspiration. During expiration, you will hear only one second heart sound – there is simultaneous closure of the aortic and pulmonary valves. During inspiration, there is a physiological splitting of the second sound with closing of the aortic valve occurring a little ahead of the pulmonary valve and the sound produced by closing of aortic valve is louder than that produced of the closing of the pulmonary valve except in patients with pulmonary hypertension. The pressure inside the thoracic cavity is negative or below atmospheric pressure – causing a suction effect on structures that can be dilated. (In positive or above atmospheric pressure, it will compress the structures in the thoracic cavity.) The more negative the intra-thoracic pressure is, the more the heart and lungs are dilated. When the heart is dilated, it allows more blood to return especially to the right heart – more blood will return from the systemic circulation. There will be an increase volume of blood to the right heart causing a delay of the closing of the pulmonary valve during inspiration. In children with thin chest wall or patients suffering from left ventricular failure, a third heart sound can be heard and that will coincide with filling of blood in the ventricles. Rarely, there is a fourth heart sound that can be heard and that will coincide with atrial contraction. In some abnormal conditions, the third and fourth heart sounds may be accentuated so that what you will hear in the stethoscope will be triplets of sounds resembling the sound that is produced by galloping horses called a gallop rhythm. Certain abnormal conditions like an infection in the heart may damage the cardiac valves and there are two types of lesions that may occur in the cardiac valve: stenosis and incompetent cardiac valve. In stenosis, the valve cannot open completely because of the hardening of 3 Shannen Kaye B. Apolinario, RMT Type of lesion Stenosis Incompetent Stenosis Incompetent Timing of murmur Diastole Systole Systole Diastole Diastole – ventricular relaxation Systole – ventricular contraction The Pericardium Pericardial fluid Parietal pericardium Visceral pericardium The heart is covered by a membrane which is made up of connective tissue – the pericardial sac or pericardium. This connective tissue that makes up the pericardium is less distensible. Presence of this will also prevent overstretching of the cardiac muscle when the cardiac size increases. The pericardium is made up of two membranes: visceral and parietal pericardium. The visceral pericardium is the membrane directly attached to the anterior surface of the myocardium. When the visceral pericardium is reflected back, it forms the parietal pericardium. The space in between the two membranes is filled with 30cc of pericardial fluid. The importance of the pericardial fluid is to lubricate the heart facilitating the movement of the heart when it contracts. (2) Groups of Myocardial Cells 1. Automatic Cells An automatic cell is a cell that is capable of spontaneously generating its own action potential independent of extrinsic nervous stimulation. In the case of myocardial cells, it is independent of automatic stimulation. Aside from generating its own action potential, the cells of the heart are capable of transmitting or conduction action potentials throughout the heart. Structures that make up the hearts’ conduction system: Synoatrial (SA) node = located at the junction of superior vena cava and right atrium. Atrioventricular (AV) node = located posteriorly on the right side of interatrial septum. It is divided into three zones: o Atrionodal (AN) zone – most proximal zone, a transitional zone between the right atrium and AV node o Nodal (N) zone - middle If the other automatic cells are hyperpolarized. With each depolarization. Apolinario. The membrane is permeable to chloride at rest. RMT -60 mv 3 4 250-300 milliseconds hyperpolarization Action potential of an automatic cell. the more sodium ions will enter the cell. Intracellular Increase K+ Negatively charged proteins Decrease Na+ Decrease Cl- Extracellular Decrease K+ Increase Na+ Increase Cl- Resting Membrane Potentials: Neurons = -70mv Skeletal muscle = -90 mv SA node = -60mv Ventricular muscle = -90mv Gastrointestinal smooth muscle = -60mv The resting membrane potential is different in each cells because of the potassium leak channels. The Na-K pump will extrude sodium ions. (44m) 2. The bundle of HIS forms right and left bundle branches. The more potassium leak channels present on the membrane. Since there are many potassium leak channels on the membrane of the skeletal muscle and there is a concentration gradient for potassium. they remain open for a long time allowing K+ to continuously move out so that at some point. it can still contract. in some abnormal conditions.3 – repolarization – re-establishing the RMP. When the K+ gated are closed.SA node . The SA node is the primary pacemaker of the heart because it is the fastest that can generate an action potential. The main extracellular cation is sodium. brought about by the closure of fast voltage gated Na channels and opening of slow voltage gated K channels.o Nodal His (NH) zone – most distal. 0 4 2 -90 mv 3 Skeletal muscle action potential: 5-30 millisecond Phase 4 – Resting Membrane Potential (-90mv) – membrane is highly permeable to potassium because of the presence of many potassium leak channels. Overdrive suppression is the increase frequency of discharge of an action potential from an automatic cell will diminish the automaticity of other automatic cells. the MP will go below the resting level = hyperpolarization. continuing to extrude sodium ions. more K+ will move out of the cell. the RMP will be restored Automatic Fiber Action Potential 1 0 2 4 Properties of Myocardial Cells 1st Property: Automaticity – generation of action potentials 4 Shannen Kaye B. it will remain active. the more the other automatic cells will become hyperpolarized. the more sodium ions will be extruded from the cell that would cause the cell to be hyperpolarized. But in a normally functioning heart. Non-automatic cells are the cardiac muscle cells present in the atrial wall and ventricular wall.2. Since these K channels are slow. a certain amount of sodium ions will enter the cell that will create a concentration gradient for sodium that will activate the Na-K exchange pump. Also present inside the cell are negatively charged molecules including proteins which are large molecules so they remain inside. even if you cut the automatic innervation to the cardiac muscle. The presence of non-automatic cells in the heart. Phase O – depolarization – opening of fast voltage gated Na+ channels Phase 1. The left bundle branch will divide to form the posterior and anterior fascicles. they will become less excitable. PHOTO: The cardiac conduction system All of these cells are automatic cells and can generate own action potential. there is a concentration gradient for sodium but the membrane is only slightly permeable to sodium ions because of there are only few sodium leak channels – most sodium will remain outside. chloride will eventually get out. The SA node will fire at a high rate of 75-80 beats per minute with each action potential that will depolarize other automatic cells. they can be stimulated to generate their own action potential. all action potentials are generated by the sinoatrial (SA) node and is referred as the primary pacemaker of the heart while the other automatic cells are latent pacemakers. The left posterior and anterior fascicles as well as the right bundle branch will then connect with the Purkinje fibers that are present mostly at the apex of the heart. When the overdrive stops. connects with the bundle of His 1 Purkinie system/ventricular conduction system = made up of bundle of HIS and purkinje fibers o Bundle of HIS – located at the interventricular septum. the more they will become less excitable. The average heart beats per minute is 75-80 beats per minute. the tendency is for potassium to move out – decreasing the amount of positively charged ions inside. Non-automatic cells Non-automatic cells cannot generate own AP and are specialized mainly for contraction. To maintain the concentration of Na and K inside the cell. They are called latent pacemakers because although they do not normally generate action potential. The primary pacemaker of heart is the one that determines the heart rate – number of heart beats per minute. the more Na-K pump will be activated. making the membrane potential more negative and vice versa. it allows the chloride ions to move in but because of the presence of the negatively charged ions inside the cell. 2 K in). and the more their automaticity will be diminished. the activity of Na-K pump will not stop immediately. you have the activity Na-K pump (3 Na out. The more frequent the other automatic cells are depolarized. These things stabilize the RMP of the cell to -90mv. Occurs rapidly due to opening of fast voltage-gated Na channels = Na influx then reaches the threshold voltage of -60 mv resulting to depolarization. it will open up slow. straight line. occurs slowly. Parasympathetic or vagal stimulation will hyperpolarize the SA node. The increase membrane permeability to potassium is responsible for the -90 mv RMP. Ca++ channels are still open Phase 1 – initial phase of repolarization – brought about mainly by slow voltage gated K+ channels Phase 2 – plateau – the amount of K+ that goes out is equal to the amount of Ca++ that goes in. it is less excitable and the duration of the membrane pre-potential is longer or delayed generation of action potential. K channels open Na leakage. norepinephrine released by sympathetic nerves will bind with the B1 receptor in the SA node resulting to an increased permeability to Na and Ca causing hypopolarization of the SA node. the neurotransmitter released (NTA) released is acetylcholine (Ache). no hyperpolarization. it is open for a long period of time thus it does not reach hyperpolarization Similarities and differences with the action potential of skeletal and cardiac muscles: Similarities: -90 mv RMP. But repolarization cannot occur rapidly because of the long lasting Ca channels are still open. fast-paced depolarization Differences: repolarization. the Ca++ channels will close leaving only the K+ channels open that will bring about the final phase of repolarization Phase 3 – final phase of repolarization Phase 4 . Decrease K -40 mv -50 mv -60 mv 250-300 milliseconds Action potential of an automatic cell (same thing happens in SA node. Phase 0 – Depolarization. In parasympathetic or cholinergic stimulation. (The main factor responsible for depolarization is Na influx) Peak of the spike – Na channels closes. straight line. no electrical activity.-90. bundle of HIS) With parasympathetic or vagal stimulation. The slow rise in membrane potential is called the pre-potential or slow diastolic depolarization. Ca influx and K efflux Midway of repo: Ca channels close. AV node. Somewhat inclined. Hyper: prolonged opening of K channels Non-automatic Fiber Action Potential (ventricular muscle) PHOTO: Action potential in the ventricle (250-300 milliseconds) Activation of slow (inclined) voltage gated long lasting Ca++ channels allowing Ca influx with some Na influx = MP will become less negative RMP .2. RMT . No hyperpolarization –Although the K+ channels can remain open for a long time. it increases permeability to K+. Apolinario. duration PHOTO: Action potential of the SA node PHOTO: Action potential of the atrium 5 Shannen Kaye B. When Ache binds with muscarinic 2 receptors in the SA node. SA node is inhibited. membrane potential increases. allowing more K+ efflux. When the membrane potential reaches -20 mv. The opposite happens with sympathetic stimulation. making it more excitable and the heart rate increases.-90 RMP is re-established. because of the plateau. Voltage gated K channels will open allowing K efflux. At the end of the plateau. there is hyperpolarization like in the skeletal muscle The increase in sodium leakage and a decrease in the membrane permeability to potassium will account for the automaticity of the SA node. long lasting voltage gated Ca channels = Ca influx. Inclined. K channels open. depolarization occurs slowly Phase 1. it is stable Phase 0 – depolarization.Difference from the AP of skeletal muscle: Duration is longer – 250-300 millisecond RMP is less negative . heart rate decreases. There is more Na leak channels. If it is hyperpolarized.-60 mv Phase 4 – slow rise in membrane potential and is unstable.3 –Repolarization. it is absolute refractory because all the voltage gated sodium channels are open and it is not able to re-open the already open sodium channels. 2nd Property: Rhythmicity It is said that the SA node generates the action potentials at regualr intervals. Photo: Normal sinus rhythm PHOTO: Relationship between action potential and contraction in the ventricle A contraction cannot be elicited unless the ventricle is almost completely relaxed.20 sec 0.02 sec Skeletal muscle 0.13 sec 0. Even if the heart rate increases. no amount of stimulus intensity will be able to re-excite the membrane of that cell. that is still called the sinus rhythm. that will open up more and more voltage gated Na channels so that its depolarization increases its amplitude. The coronary arteries supply blood and oxygen to the cardiac muscle thus when it is compressed.55 sec 0. when the ventricles are relaxed. More K+ conductance than Ca++ conductance that will make the duration of the plateau shorter and not sustained as compared to that of the ventricle. it compresses the coronary arteries. the Na channels are already close but it is still absolute refractory because Na channels are voltage gated and they only open at a certain voltage or membrane potential near the critical firing level of about -60mv more so if the membrane potential is at its resting level. PHOTO: Changes in action potential amplitude and upstroke slope as action potentials are initiated at different stages of the relative refractory period of the preceding excitation As the membrane potential reaches the relative refractory period as well as the RMP.001 sec In Absolute or Effective Refractory Period (ARP). Apolinario. same thing happens in the SA node. In phases 1 and 2. RMP.05 sec Heart rate 200/min 0. One cannot elicit successive action potentials or contractions without tetanic or sustained contractions in the cardiac muscle = allow more time for ventricular filling. There is longer period of relaxation.25 sec 0. It covers the whole of depolarization until 1/3 of the repolarization phase.Similarities and differences between the ventricle and atrium: Similarities: same.004 sec 0. o Repolarization phase is shorter in atrium than in the ventricle Periods of Refractoriness ARP RRP The importance of prolonged duration of refractoriness is for the ventricles to be filled with blood resulting to a more effective pumping action. It is far from the CFL. no fatigue. RMT . The musculature of the ventricle is thick so when it contracts. if there is stimulus later in the RRP. no tetanic contractions. there will be better perfusion of the cardiac muscle. this happens if there is tetanic contractions but in the cardiac muscle. the membrane becomes more excitable so that a stronger than threshold stimulus can be able to open up the voltage gated sodium channels and elicit a second action potential. there are no tetanic contractions. phase 1 Differences: o phase 2 – plateau. the membrane is more permeable to K+ than to Ca++. if the impulses are still generated at regular intervals. At phase 0. In the atrium. Duration Action potential ARP RRP Heart rate of 75 beats per min 0. In Relative Refractory Period (RRP). there is poor perfusion of cardiac muscle and less oxygen supply. depolarization. its level is near the critical firing level and resting level. Photo: Normal ECG 6 Shannen Kaye B.005 sec 0. in D. There is a delay in the transmission of impulses in the AV node because it has a small fiber diameter and few gap junctions – spaces or channels between the membranes of the muscle fibers that will allow ions to flow freely from one muscle fiber to the next. transmission of impulses can occur locally through gap junctions. the impulse will be transmitted to the AV node and transmission of impulses from the SA node to the AV node is facilitated by means of three internodal tracts: anterior internodal tract of Bachmann. conduction of impulses may occur locally through gap junctions. the antegrade impulse is blocked. In A. . If there is no rhythm or if it is irregular. showing the time of appearance (in fractions of a second after initial appearance at the sinoatrial node) in different parts of the heart. But since the rate will increase. Conduction Speed in Cardiac Tissue SA node Atrial muscle AV node Bundle of His Purkinje fibers Ventricular muscle Conduction rate (m/sec) 0. there is a delay in the transmission of impulses so the velocity of conduction decreases at the AV node and this is called the AV nodal delay. 7 Shannen Kaye B. Transmission of impulse in heart: basal. a bidirectional block exists in branch R. middle internodal tract of Wenckeback and posterior internodal tract of Thorel.P wave – represents atrial depolarization QRS complex – represents ventricular depolarization When seeing a normal sinus rhythm. the rate of firing will decrease but if the impulses are generated at regular intervals. an excitation wave traveling down a single bundle (S) of fibers of continues down the left (L) and right (R) branches. The part of the heart that will depolarize last is the postero- Photo: Sinus bradycardia On the other hand. the heart rate will increase but if the impulses are generated at regular intervals. With regards to the right and left atrium. the wave is blocked in the L and R branches. it is now called sinus bradycardia. take note of the interval between successive QRS complex – regular interval. Fastest is in the Purkinje fibers because of the large fiber diameter. The importance of AV nodal delay is for the ventricles to remain in a relaxed state for a longer period of time allowing more time for the ventricular filling and to ensure that the atria and ventricles will not contract simultaneously. that is still sinus rhythm but this time.the AV nodal delay.05 1 0. Reentry Photo: Transmission of the cardiac impulse through the heart. The depolarization wave enters the connecting branch (C) from both ends and is extinguished at the zone of collision. Most of the delay will take place between the AN and N zones of the AV node. All impulses from a normal functioning heart will come from the SA node. In C. From the AV node. In B. a unidirectional block exists in branch R. during moderate to heavy exercise. but the retrograde impulse is conducted through and re-enters bundle S. RMT Photo: The role of unidirectional block in re-entry. In these three conditions. take note of the interval between successive P waves – regular interval. In the atria and ventricles. Take note that the tips of the fibers of the SA node are directly connected to the right atrial muscle cells so there is direct transmission of impulses from the SA node to the right atrium. Apolinario. in cold temperatures or if there is vagal over stimulation that inhibits the SA node. When the impulse reaches the AV node. that is still sinus rhythm. it is now called arrhythmia.05 1 4 1 antero-basal apex postero-basal Photo: Sinus tachycardia The heart rate may increase with sympathetic stimulation. it is now called sinus tachycardia. 3rd Property: Conductivity Conduction speed is lowest in the AV node (not in the SA node because it is generation). and increase temperature during fever. From the SA node. The smaller fiber diameter and fewer gap junction causes increased resistance to impulse conduction . the impulse will then travel to the bundle of His then to the left and right bundle branches then to the Purkinje fibers then it would stop (from antero-basal apex end). From the bundle of His. there will also be three contractions in the ventricles. RMT . in the ventricle. the ratio of the atrial to ventricular depolarization is 2:1 or 3:1. For 20 seconds. the ventricle will not contract because no impulses will reach the ventricles but there are pacemaker cells in the ventricles – the bundle of His and Purkinje fibers. when it reaches the area that is blocked. Take note that extrasystole can only be elicited during the mid or late diastole. This time. Not all the impulses reach the ventricles but since there are impulses that can reach the ventricles. What happens is P-P-P-P. From the left and right bundle branches to the apex of the heart but there is a connecting fiber between the right and left bundle branches. The difference from the normal is that it has a longer duration of the AV nodal delay. In the synchronised contraction. Coming from the SA node to the AV node to the bundle of His. So when it contracts. Because of this phenomenon. B – Both left and right bundle branches are blocked so there is no impulse transmission to the apex of the heart as well as to the connecting fiber. The one that goes to the connecting fiber can now go to the apex but can also go back to the area that is blocked. the transmission of impulse is blocked while that coming from the left will re-enter the area where the impulse came from. the impulse will be transmitted to the left and right bundle branches. it becomes out of refractory/out of refractoriness so it can go back. C. The impulse that is supposed to go the right bundle branch is blocked but the left bundle branch goes to its normal route – to the apex and to the connecting fiber. Apolinario. there will be no impulse coming from the SA node. there will be another contraction and this is premature contraction or extrasystole. What happens is P-P-QRS. First-degree block. 1st degree heart block – Incomplete heart block. Another contraction can be produced only during the mid or late diastole when the muscle is almost completely relaxed (Note: “almost” but not yet relaxed). this is called reentry or circus movement. When activated. the ventricles will also contracts three times but atrial contraction happens first than ventricular contraction causing an AV nodal delay.20 sec). it is 30-40 beats per minute. other parts of the atria will be activated. Third-degree block. If the contraction in the atria is 75 beats per minute. PHOTO: Frequency summation and tetanization In wave summation in the skeletal muscles. B. Reentry or circus movement is possible because the distance travelled by this impulse is longer compared to other one which is blocked so it becomes refractory. C – Only one bundle branch is blocked (right bundle branch). the Purkinje fibers will generate its own impulse causing the ventricles to contract at a rate that is dictated by the Purkinje fibers. all of these are abnormal conditions. PHOTO: AV blocks. Another abnormal condition is the presence of a premature contraction or an extrasystole wherein another contraction happens in response from an impulse that will not come from the SA node. The firing of Purkinje fibers is slower than the SA node. The atria will be contracting normally at a rate that is dictated by the SA node. and there will be an ectopic fossi – impulse coming from other sources. the magnitude of the 2nd contraction is lower than the first. 2nd degree and 3rd degree heart block. No impulses from the SA node will be able to reach the ventricles. there will be more releasing of calcium ions that will increase the force of contraction. Based on the spacings in the photo. there is an area that will contract and there is an area that will relax. D – Since the right bundle branch is blocked. there is atrioventricular depolarization happening. In cardiac muscle. it will escape from the overdrive suppression and this is called the ventricular escape. Initially. P-P-QRS. Ectopic Tachycardias Atrial contraction Ventricular contraction AV nodal delay Most of the blocks takes place in the AV node so that it will produce the 1st degree. The ratio of ventricular depolarization is still 1:1. there is atrial contraction that is initiated by the impulse from the SA node. For example.A – Normal direction. if there is another impulse. this is the path that is responsible for atrial or ventricular fibrillation/flatter. that is 75 beats per minute. So that when it contracts – three contractions in the atria. it goes round and round that’s why it is called circus movement. the whole atria or the whole ventricle. 3rd degree heart block – Complete heart block. Second-degree block (2:1). the PR interval is 0. if three maximal stimuli is applied successively. calcium ions have not yet returned to the sarcoplasmic reticulum and when another stimuli is applied. All impulses from the SA node can still be transmitted to the ventricles. 2nd degree heart block – Not all impulses from the SA node will reach the ventricles. the magnitude of the 2nd contraction is higher than the first because in the muscle. so that during atrial and ventricular contraction. Since the distance is longer. A. The two are latent pacemakers and they are also automatic cells. the latent pacemaker in the ventricle specifically the Purkinje fibers will be activated. if the atria will contract three times. note the dissociation between the P waves and the QRS complexes 8 Shannen Kaye B. The normal ratio between atrial and ventricular depolarization is 1:1. It is not able to elicit an extrasystole during systole or early diastole because of the long duration of the Absolute Refractory Period. this is still an incomplete heart block.28 second (normal: <0. What separates the individual muscle fibers is the Z line that is why the area between two Z lines will form a sarcomere. it can’t store large quantities of calcium ions that will provide for full contraction so there has to be another source of Ca++ for the cardiac muscle contraction and that is the extracellular fluid (ECF). Striated means that the muscle fibers are distinctly separated from one another. there are more mitochondria as well as active capillaries in the cardiac muscle and that is important because the main source of energy for cardiac muscle contraction is oxidative metabolism. PHOTO: “Syncytial. When either cardiac or skeletal muscle is stretched. as evidenced by the rapid rise in resting tension in the middle of the bell-shaped AT curve. Compared to the skeletal muscle. Contractile proteins present: Thick filament . Apolinario. It is. More mitochondria and active capillaries. The difference between the skeletal and cardiac muscle cell is that the membrane of the cardiac muscle branches out to reconnect with the membrane of the next muscle fiber so that the force generated with one muscle fiber can be transmitted to the other muscle fibers as well. Meaning to say.Remember that one of the important factors that will determine the force of cardiac muscle contraction is the volume of blood that will stretch the muscle before contraction. Sarcoplasmic reticulum. it can be transmitted rapidly causing the whole bundle to be depolarized at the same time and to contract as a single unit and this is called a syncytial type of arrangement of muscle fibers. Connective tissue. Activity of the heart is not controlled by the cerebral cortex. The sarcoplasmic reticulum in the cardiac muscle is less well developed. The bell-shaped dependence of active tension on muscle length is consistent with the sliding filament theory of cardiac and skeletal muscle. 4th Property: Contractility Important characteristic of a cardiac muscle: Involuntary. tropomyosin Meromyosin. Presence of connective tissue that will prevent over distension or overstretching of a cardiac muscle when the cardiac size increases. difficult to stretch cardiac muscle beyond its optimal sarcomere length. the greater the stretch of the cardiac muscle will be and the greater the force of contraction will be. Just like the skeletal muscle cell. The intercalated disk is present on the Z line.myosin Thin filament – actin. C protein – forms the scaffold or suport of the thick filament 9 Shannen Kaye B. however. The syncytial arrangement of muscle fibers is important because it will provide synchronized contraction of the atria and ventricles that is important for the pumping action of the heart. the more blood will be filled in the ventricles. The longer the relaxation phase. And because the transverse tubular system in the cardiac muscle is more developed – it has a bigger diameter. . it can allow more Ca++ from the ECF to enter the cardiac muscle cell. The cardiac muscle cell anatomically is striated but functionally or physiologically. Nebulin – forms the scaffold of the thin filament α actinin – will connect the thin filament to the Z line Titin – connects the thick filament to the Z line Tropomodulin – regulates the length of the thin filament Elastic tissue. Present in the intercalated disk are channels that will allow ions to flow freely from one muscle fiber to the next so that when an action potential is generated anywhere in a bundle. If the muscle is then stimulated to contract maximally. It will also provide synchronized relaxation of the atria and ventricles that is important for filling of blood in the different chambers of the heart. The difference between total tension and resting tension at any given length is the force produced by contraction (e. RMT PHOTO: Cardiac muscle (panel A) has high resistance to stretch when compared with skeletal muscle (panel B). active tension – AT). the cardiac muscle cell is smaller Either binucleated or mononucleated Striated. to connect one muscle fiber to another by means of gap junctions. there is an increase in resting tension (RT). Compared to skeletal muscle cell. Fair amount of elastic tissue that will enable the chambers of the heart to dilate to accommodate a greater volume of blood. Its function is to separate one muscle fiber from another but at the same time. There is a decrease in the magnitude of the 2nd contraction because the relaxation phase is not yet complete so the filling of the blood is less resulting to less stretch of the muscle and less force of contraction. it is controlled by the autonomic nervous system although there are automatic cells present in the heart.g. Smaller. it is a syncytium. the cardiac muscle is striated. troponin. Presence of the intercalated disk.” interconnecting nature of cardiac muscle fibers. it generates more tension (termed total tension – TT). Pre-ganglionic fibers from T3. Excitation-Contraction Coupling potassium ions pumped into the cell so that it will create a concentration gradient for sodium – increased concentration outside. ventricular conduction system or the Purkinje system as well as the atrial and ventricular muscle. The difference of this from the skeletal muscle is that the Ca++ from the SR will not move out unless there is a trigger that will cause the Ca++ to move out. Inside the cell. and there is very little. This poor force of contraction has to be made strong by giving cardiac glycosides (e. RMT First. even in the resting state or resting length. this will activate the voltage-gated calcium channels of the membrane of the T tubule and that will allow Ca++ to enter from the extracellular fluid (ECF) to the inside of the cardiac muscle cell. The effect of Ache on the myocardial cells is to increase membrane permeability to K+ so that will hyperpolarize the myocardial cells inhibiting them or decreasing cardiac activity. and T5 segments (T = thoracic). Arrangement of Muscle Fibers When the heart contracts. Chronotropic regulation: Sympathetic Increased frequency of discharge of the SA node Increased the heart rate Parasympathetic Decreased frequency of discharge by the SA node Decreased the heart rate . The blue line represents the resting tension – tension that develops in the muscle before contraction. the sodium-potassium pump is activated that will pump three sodium ions out in exchange for two 10 Shannen Kaye B. it rotates slightly to the right and that will expose the cardiac apex. On the membrane of the sarcoplasmic reticulum is another calcium pump. the main problem is poor force of contraction of the ventricle. The importance of that is the different chambers of the heart can accommodate a large volume of blood with little increase in pressure. T4 and T5 will synapse with the sympathetic ganglia and this is called the sympathetic chain. atrial muscle. it is expected that the muscle will relax but for the muscle relax. there are myofilament and sarcoplasmic reticulum (SR). Also on the membrane of SR are ryanodine receptors and these receptors are calcium-gated calcium channels. That is why it has two sources of Ca++ compared to skeletal muscle – the SR and ECF. The structures in the heart that receive parasympathetic or vagal innervation are the SA node. the force of contraction is stronger. Present on the membrane or sarcolemma is a calcium pump. Parasympathetic: CN 10 Acetylcholine + M2 SAN AVN Atrial muscle On the other hand. Present on the membrane of the T-tubules are voltage-gated calcium channels. low concentration on the inside. What happens is when a membrane is depolarized. AV node. It needs Ca++ from ECF to trigger movement of Ca++ from SR into the cytoplasm. digitalis). with repolarization. The effect of NE at the myocardial cells is to increase membrane permeability to Ca++ and Na+ so that will make the myocardial cell more excitable and therefore increased cardiac activity. atrioventricular (AV) node. Ca++ has to be removed. Ca++ is removed by the activity of calcium pump on the membrane of the SR that will actively transport Ca++ back into the SR. the difference between active and passive tension is smaller compared to skeletal muscle. The arrangement of muscle fibers is synospiral and bulbospiral. nothing will activate the sodium-calcium pump so Ca++ will remain inside the cell and that can be utilize to increase the force of ventricular contraction. If there is no concentration gradient for Na+. T4. if any.Above is a graph that shows the importance of the presence of elastic tissue in the cardiac muscle. the sympathetic nerves that innervate the heart originate from T3. Autonomic Innervation of the Heart How does the Autonomic Nervous System (ANS) regulates the cardiac activity? Sympathetic: T3 T4 T5 SA node AV node Purkinje system Atrial muscle Ventricular muscle Norepinephrine + β1 receptor PHOTO: Excitation-contraction coupling in the heart requires Ca++ influx through L-type Ca++ channels in the sarcolemma and T tubules. With repolarization. Post-ganglionic fibers from the sympathetic chain will bind with β1 receptors in the heart and the neurotransmitter agent (NTA) released by these sympathetic nerves is norepinephrine (NE). Invagination of the sarcolemma will form the T-tubules. Apolinario. Sympathetic nerves innervate ALL structures in the heart either automatic and non-automatic so that will include the sinoatrial (SA) node. Na+ will not be extruded so that will not create a concentration gradient for Na+. calcium-sodium exchange pump. Another means to remove Ca++ is through the activity of the calcium pump on the sarcolemma that will actively transport Ca++ back into the ECF. So the vagus nerve will bind with muscarinic 2 receptors in the heart and the NTA released is acetylcholine (Ache). only the proximal part of the bundle of His. Because of the many elastic tissue in the cardiac muscle. But the most important means by which calcium is extruded from the cardiac muscle cell is through the activity of the sodium-calcium antiporter. If there are already many Ca++. In patients suffering from heart failure. vagal innervation to the ventricles. sodium-potassium exchange pump and the last two are antiporters. That will now activate the sodium-calcium exchange pump that will pump three Na+ in. If this pump is inhibited. in exchange for one Ca++ that is pumped out of the cell and that is the main means by which Ca++ is extruded from the cardiac muscle cell. The main mechanism of action of cardiac glycosides is to inhibit the sodiumpotassium pump. Initially.g. parasympathetic innervation to the heart is carried by the vagus nerve which originates from the medulla. The trigger is also Ca++ from the ECF that will bind with ryanodine receptors hence it is called calcium-gated calcium channels. The red line represents active tension – tension that develops in the muscle during contraction. The heart can rotate when it contracts because of the arrangement of muscle fibers. Some of this Ca++ will immediately bind with troponin C forming the calcium-troponin C complex that will initiate muscle contraction but some of the Ca++ will bind with the ryanodine receptors on the membrane of SR activating the calcium-gated calcium channels that will allow Ca++ to move out from the SR to the cytoplasm to bind with troponin C. passive tension increases in the muscle and it can dilate so that when the cardiac muscle fiber contracts. the amplitude of the different ECG waves. The electrode of the left arm is designated as the negative electrode that of the left leg as the positive electrode. it is preferable to use lead II because it approximates the direction of impulse transmission in the heart – right arm is negative. regulation of heart rate is called chonotropic regulation. PHOTO: Einthoven triangle illustrating the electrocardiographic connections for standard limb leads I. decreasing the heart rate. In contrast. and the greater will be the force of ventricular contraction. the electrode that is on the right arm is the negative electrode that of the left arm is the positive electrode. bipolar limb leads are formed or standard limb leads. Right arm (negative) Left leg (positive) Lead II 11 Shannen Kaye B. parasympathetic stimulation will prolong the duration of the AV nodal delay allowing more time for ventricular filling so the more the ventricles are filled with blood. it decreases the force of atrial contraction and it has no direct effect on the force of ventricular contraction. In order to have an electrical potential difference between two electrodes. II. In lead I.electrical and mechanical events taking place in the heart from the beginning of one heart beat initiated by an impulse from the SA node to the beginning of the next heart beat also initiated by an impulse from the SA node. Sympathetic stimulation increases the force of contraction of both the atria and ventricles. it is always positive. There are three bipolar limb leads – Lead I. On the other hand. Lead III represents electrical potential difference between electrodes that are placed on the left arm and on the left leg. increasing the heart rate. the more the ventricular wall is stretched. buma-VAGAL ang heart rate and velocity of conduction. RMT . II and III. It has no direct effect but it has an indirect effect. Inotropic regulation Sympathetic Increased force of atrial and ventricular contraction Parasympathetic Decreased force of atrial contraction Regulation of the force contraction of the myocardial cells or inotropic regulation is by increasing membrane permeability to Ca++. that is. repolarization of the atria and depolarization and repolarization of the ventricle Mechanical events – contraction or relaxation of the atria and ventricles Electrical events The electrical events will precede the mechanical events. By placing electrodes particularly on the four extremities. In one lead. Sympathetic stimulation will increase the velocity of conduction of impulses in the heart so it will decrease the duration of the AV nodal delay. parasympathetic or vagal stimulation will inhibit the SA node. Electrical events – depolarization. The electrode that is placed on the right arm is always negative and on the left leg. All the electrical events taking place in the heart can be recorded by the electrocardiogram (ECG). let’s look at how the autonomics regulate cardiac activity: First. Dromotropic regulation Sympathetic Increased velocity of conduction Decreased duration of AV nodal delay Parasympathetic Decreased velocity of conduction Increased duration AV nodal delay Regulation of the velocity of conduction of impulses in the heart is called dromotropic regulation. Lead II will approximate the direction of impulse transmission in the heart. To get an ECG tracing. The sympathetic nervous system will increase the activity of the SA node so that this stimulation will increase the frequency of discharge of action potentials from the SA node. Cardiac Cycle Cardiac cycle is the sequence of events . These leads will represent electrical potential difference between two electrodes placed on two different extremities. electrodes are placed on the four extremities of the subject as well as on different locations on the chest wall. left leg is positive (from base to apex). parasympathetic stimulation decreases the velocity of conduction of impulses in the heart prolonging the duration of the AV nodal delay.In relation to this. As for parasympathetic stimulation. one electrode is arbitrarily designated as the negative electrode and the other one is the positive electrode. Lead II represents electrical potential difference between electrodes that are placed on the right arm and on the left leg. Lead I represent electrical potential difference between electrodes that are placed on the right arm and on the left arm. the electrode is positive when it is located nearer on the apex of the heart. So that when asked to measure the duration of the different ECG waves. Apolinario. *** In parasympathetic or VAGAL stimulation. This electrodes act as sensors so that it will be able to pick up electrical potentials produced by the myocardial cells so that what is seen on the ECG tracing will represent electrical potentials and electrical activities of the myocardial cell. and III. The electrode of the right arm is designated as the negative electrode that of the left leg as the positive electrode. the positive electrode is on the left leg. if the electrode moves toward a positive electrode. it is actually the S-T interval. From the beginning of P to the beginning of the QRS complex is the P-R interval. There is a straight line because of the equal conductance of Ca+ and K+. it is recorded as an upward or positive deflection. So in the ventricles the first part of the ventricles that will depolarize is the last part to repolarize and the last part to depolarize will be the first part to repolarize. the phase of repolarization that represents the S-T segment is the plateau or phase II. there will an AV nodal delay ad that is represented by the straight line called a P-Q or P-R segment. Remember that the impulse is generated from the SA node transmitted to the AV node so the direction of impulse transmission in the atria is it moves towards a positive electrode. When the impulse reaches the AV node.atrial depolarization. T wave is only a part of ventricular repolarization because ventricular repolarization starts at the end of QRS complex. it is recorded as a downward or negative deflection. there is an isoelectric line or the S-T segment. from the end of S to the end of T. Recall the action potential generated in the ventricle. In the ventricles. ECG Rules: Depolarization (+) electrode = upward QRS complex will represent ventricular depolarization. The P-R interval will cover the P wave representing atrial depolarization and the P-R segment that represents AV nodal delay. If ever there is an ECG wave that will represent atrial 12 Shannen Kaye B. it will appear as a downward or negative deflection because the direction of repolarization in the atria follows the direction of depolarization – repolarization is toward a positive electrode. P-R segment (isoelectric) S-T segment (isoelectric) PHOTO: Depolarization of interventricular septum from the left to right bundle branch PHOTO: Important deflections and intervals of a typical scalar ECG. and T wave represents ventricular repolarization. RMT . it is recorded as negative or downward deflection and if repolarization will move away from a positive electrode. So when it is said ventricular repolarization. In the QRS complex. if depolarization will move away from a positive electrode. Apolinario. not just the T wave. The P-R segment starts at the end of P up to the beginning of the QRS complex. Above is an example of an ECG tracing that shows electrical events in the heart in one cardiac cycle. During systolic phase of the Depolarization away from (+) electrode = downward Repolarization (+) electrode = downward Repolarization away from (+) electrode = upward Why is there an upward or positive deflection and a downward or negative deflection? The rule in ECG is that if depolarization will move towards a positive electrode. again it is moving away from a positive electrode so the S wave which represents depolarization of the posterobasal part of the ventricle is recorded as negative or downward deflection. Repolarization will occur in the opposite direction: from posterobasal apex anterobasal. So from the end of S wave to the beginning of T wave. It is moving away from a positive electrode because from the apex. The T wave will represent only the phase III of repolarization or the final phase of repolarization and it is a positive or upward deflection. So which part of the heart will depolarize last? Usually it goes from the anterobasal apex posterobasal so when the wave of depolarization moves from the apex to posterobasal part. there is no change in membrane potential. On the other hand. the atrial and ventricular muscles will contract and it is called the systole. It is a complex made up of three waves. it is a positive deflection. Then there is a second downward deflection which is the S wave. QRS wave or complex represents ventricular depolarization. That is why the P wave is recorded as an upward deflection. Mechanical events Following depolarization. it will go up hence it is recorded as an upward or positive deflection. In repolarization. The P wave represents atrial depolarization. P wave P wave . it is recorded as an upward or positive deflection. R wave is a very high positive deflection that represents depolarization of the cardiac apex that is definitely towards a positive electrode. the repolarization does not follow the direction of depolarization.repolarization. This means that in the atria. the first part to depolarize is also the first part to repolarize and the last to depolarize is also the last part to repolarize. It is a straight or isoelectric line because of the delay on the impulse transmission at the AV node. The positive electrode is in the left leg [it is moving from the left to right bundle branch] so it is moving away from a positive electrode that is why the Q wave which represents the depolarization of the interventricular septum and is recorded as a downward or negative deflection. there is an initial negative or downward deflection that represents depolarization of the interventricular septum which will occur from left bundle branch to right bundle branch. unlike in the atria. Remember that in lead II. There is no ECG wave that represents atrial repolarization because atrial repolarization occurs simultaneously with ventricular depolarization. When ventricular pressure exceeds 80 mmHg. there will be atrial filling. in the ECG that is recorded as the P-R segment. There will be a condition again wherein the SL valves are now closed.ventricular filling VP – ventricular pressure At the beginning of one cardiac cycle. The importance of the AV nodal delay is that it will provide more time for ventricular filling. the AV valves are still closed so there is no change in ventricular volume but since the ventricles are in a relaxed state.cardiac cycle. the ventricular pressure increases. filling. . the atrium and ventricles are all relaxed – atrial systole and ventricular diastole. But remember that the AV valves does not over-bulge into the atria when the ventricular pressure is increased because when the ventricles contract. In the process. there is 80% of ventricular filling. before an impulse is generated from the sinoatrial (SA) node. ventricular pressure decreases and this is called isovolumic relaxation. When the impulse reaches the AV node. AP (V wave) AP > VP open AV valves rapid inflow diastasis – reduced inflow of blood to the ventricles atr. atr. VP dec. there will be a decrease in the atrial pressure.53 of a second and this happens at the heart rate of 75 beats per minute. diastole dec. The response of the ventricular muscle to repolarization is to relax so there will be ventricular diastole therefore ventricular pressure will start to decrease. When the atria are contracting. Apolinario. atrial filling vent. The response of the ventricular muscle to depolarization is to contract so following ventricular depolarization will be ventricular systole. Wenckeback and Thorel.semilunar vent. depo (QRS) atr. AP (a wave) An impulse will be generated from the SA node transmitted to the AV node. But there is a short interval of time between ventricular diastole and closure of SL valves which is called protodiastole. depo (P wave) AVN VCS delay (P-R segment) vent. the duration of the cardiac cycle will decrease so the duration of the systole and diastolic phases is also decreased. inc. At the same close AV valves (1st heart sound) isovolemic contractions: slight inc. AP 20% VF inc. the atria will undergo depolarization recorded in the ECG as the P wave. From the AV node.decrease depo – depolarization inc.antrioventricular AVN – atrioventricular node dec. The average duration of one cardiac cycle is 0. diastole inc. blood is ejected from the different chambers of the heart. so whenever the AV valves are open. Transmission of the impulse from the SA node to the AV node is facilitated by the three internodal tracts: Bachman. the blood that is contained in the aorta will drop off to the arteries to the different organs of the body and the veins are also collecting blood so that little by little. repo vent. there is no change in ventricular volume because all the cardiac valves are closed but since the ventricles are contracting. – atrial AV . systole inc. There will be a condition wherein the SL are still closed and the AV valves are now closed. In fact. Pressure in the aorta or in the arterial system is always high so that when arterial or aortic pressure now exceeds ventricular pressure.27 second and that of the diastolic phase is longer which 0. The response of the atrial muscle to depolarization is to contract so there will be atrial systole. When the ventricles contract. When the ventricular pressure exceeds atrial pressure. there is still blood ejected to the ventricles and that will account for only 20% of ventricular filling. ventricular pressure still increases and this high pressure may push the AV valves to bulge into the atria and that will cause a slight increase in atrial pressure which is now called the C wave. VF vent. A wave is not an ECG tracing. there will be a pressure gradient and that will now close the AV valves therefore the first heart sound will be heard. the papillary muscles will contract pulling the chordae tendinae which will prevent over-bulging of the AV valves into the atria resulting to only a slight increase in the atrial pressure. The response of the atrial muscle to repolarization is to relax so atrial diastole happens. this will push open the SL valves and following the opening of the SL valves is the period of rapid ejection of blood from the ventricles to the arteries: aorta and pulmonary arteries. Since the atria is relaxed. the volume of the blood in the ventricles as well as ventricular pressure will start to decrease. When the heart rate increases. AP (C wave) VP > 80 mmHg open SL valves rapid ejection reduced ejection. But there is a greater decrease in the duration of the diastolic phase and there is a constant duration in the systolic phase when the heart rate increases. It is not needed for the atria to contract to have ventricular filling because its contraction is weak – “primer pump”. When the ventricles are contracting. repo VP > AP atr. there will be filling of blood in the different chambers of the heart. So the period of rapid ejection will now be followed by a period of reduce ejection of blood from the ventricles to the arteries and at the same time. inc. But when it is ejecting more and more blood. the impulse will now be transmitted to the ventricular conduction system (VCS) or Purkinje system and that will cause ventricular depolarization in the ECG recorded as the QRS complex. VP (S-T interval) AP > VP protodiastole close SL valves (2nd heart sound) isovolemic relaxation. there is increase in ventricular pressure and this is called isovolumic or isovolumetric contraction phase of the cardiac cycle. The duration of the systolic phase is 0. it is only a label to the increase atrial pressure during atrial systole. 80% of ventricular filling (VF) takes place when all four chambers of the heart are in a relaxed state. although it is a weak pump. 13 Shannen Kaye B. atrial pressure increases and remember that there are no cardiac valves between the atria and veins so that any increase in atrial pressure can be transmitted to the veins so that in the recording of the jugular venous pressure curve will show increase atrial pressure during atrial systole and this is called A wave. During diastolic phase.8 second.increase repo – repolarization SAN – sinoatrial node SL . there will be a delay called the AV nodal delay. Correlation of the Electrical and Mechanical Events in the Heart in One Cardiac Cycle SAN atr. Following repolarization. this will close the semilunar valves and that will produce the second heart sound. Simultaneous with ventricular depolarization is atrial repolarization and no ECG wave represents atrial repolarization. – ventricular/ventricle VF. the muscles will relax and it is called diastole. The ventricles will undergo repolarization so this is the S-T interval in the ECG. The semilunar (SL) valves are closed but the atrioventricular (AV) valves are open so that will allow blood to flow from the atria to the ventricles. RMT . systole atr. When the atria contracts. . But as the volume of blood in the ventricles decreases. It will increase slightly during atrial systole because of the additional volume of blood that will be ejected by the atria to the ventricles. all the cardiac valves are closed so there will be no change in the volume of ventricles. All throughout the period of ventricular diastole. and to the different organs of the body so the volume of blood in the aorta will decrease and that will now cause the aortic wall to recoil. While at the beginning of isovolumic relaxation. Remember that in isovolumic contraction. the aortic pressure is stable and is slightly low but it is still higher compared to the ventricular pressure. So that means at that point. blood that is contained in the aorta will now be distributed to the arteries. All of these events take place in the heart for 0. It will continually increase during the period of rapid ejection because of the increased volume that will be ejected from the ventricle to the aorta. slight increase with atrial systole because of the additional volume of blood ejected from the atria to the ventricles. there will be greater force exerted by that volume of blood on the aortic wall. it will be slightly stabilized so that the period of rapid inflow will be followed by a period of reduced inflow of blood to the ventricles called diastasis. to the arterioles. It will continue to decrease during the period of isovolumic relaxation. Again. Ventricular Pressure Curve SL valves open SL valves close – 2nd heart sound ***Atrial pressure curve – yellow dotted line Aortic pressure or arterial pressure is always high. Ventricular pressure will actually increase during isovolumic contraction and still high during the period of ejection of blood. When atrial pressure exceeds ventricular pressure. The pressure difference between the aorta and the ventricles will cause the closing of the SL valves when aortic pressure exceeds ventricular pressure. the atrial filling increases which will again increase atrial pressure and is called the V wave. the aortic pressure decreases because there will be peripheral run-off blood. During the period of reduced ejection. Atrial Pressure Curve incisura Phases: as – atrial systole ic – isovolumic contraction ejection – rapid and reduced ejection phase ir – isovolumic relaxation R inflow – rapid inflow of blood to the venticles diastasis as – atrial systole The period of ventricular systole covers from the beginning of isovolumic contraction until the end of the ejection phase while the ventricular diastole will start with isovolumic relaxation up to the end of atrial systole. the SL valves close so the second heart sound will be heard. Apolinario. It will remain low during the periods of rapid inflow of blood to the ventricles and diastasis. meaning to say. So if the volume of blood in the aorta is greater. What will happen at the end of isovolumic contraction? There will be opening of the SL valves. the first heart sound will be heard. there is a slight vibration of blood inside so there will be slight increase again in aortic pressure which is called a dichotic notch or incisura. When there is more blood filled in the ventricle. When the aortic wall recoils. *** Ventricular pressure curve – green line 1st heart sound 14 AV valves open Shannen Kaye B. Opening of the AV valves mark the end of isovolumic relaxation so there will be period of ventricular filling.8 second. From that.time as isovolumic relaxation. this will now open the AV valves which will be followed by a period of rapid inflow of blood to the ventricles and this event will account for the 80% of ventricular filling. Cardiac Cycle Ventricular pressure is initially low. there will be another impulse from the SA node beginning another cycle. RMT . Closing of the AV valves will mark the onset of isovolumic contraction. ventricular pressure will also decrease. During isovolumic contraction. heart sounds.Ventricular Volume Curve The 3rd heart sound heard in abnormal conditions is due to ventricular filling. Again. and left ventricular pressure pulses correlated in time with aortic flow. Closure of the AV valves will mark the onset of the period of isovolumic contraction so when seen at the ventricular volume curve. venous pulse. Apolinario. 15 Shannen Kaye B. there is no change in the ventricular volume. During period of rapid ejection. ventricular volume. it is a straight line – no change in ventricular volume. there is a very high increase in ventricular volume. Atrial Pressure or Central Venous Pressure (CVP) Curve a c c v PHOTO: Left atrial. RMT . At the start. The 2nd heart sound is due to the closure of the SL valves that will now mark the onset of the period of isovolumic relaxation. Heart Sounds The 1st heart sound is due to closure of the AV valves. aortic. The V wave is increase atrial pressure during isovolumic relaxation where it is simultaneous with the increase in atrial filling. all cardiac valves are closed so there is no change in the ventricular volume. all cardiac valves are closed so there is no change in ventricular volume. blood is ejected from the ventricles so the ventricular volume will decrease. There is an increase in ventricular filling coinciding with the appearance of the 3rd heart sound. Ventricular Volume Pressure Curve (Ejection Loop) A wave is increase in atrial pressure during atrial systole. It is somewhat stabilized in diastasis and a slight increase again during atrial systole. and the electrocardiogram for a complete cardiac cycle. C wave is slightly increased in atrial pressure during isovolumic contraction when the increased ventricular pressure pushes the AV valves to bulge into the atria. there is additional increase in volume with atrial systole – additional 20% of ventricular filling. In the period of isovolumic relaxation. During the period of rapid inflow. ” demonstrating changes in intraventricular volume and pressure during the normal cardiac cycle. The horizontal axis represents changes in ventricular volume and the unit is either cc or mL. Phase III – in the latter part of Phase III – the volume decreases and the pressure decreases. “ I can do EVERYTHING through Him who gives me strength” -Philippians 4:13 GOD BLESS YOU! 16 Shannen Kaye B. Phase II – the volume of blood is 130 mL and the pressure continues to increase. EW. there is period of isovolumic contraction. Point A . The letters represent each point. When the SL valves open. This is isovolumic relaxation. In relation to changes in ventricular volume and pressure. This 50 mL is actually the volume of blood remaining in the ventricles after contraction. this is now the reduced ejection. Point B . At phase II.ventricular volume is 50 mL. the cardiac cycle is divided into four phases.the volume of blood is 130 mL. At 50 mL. Reduced ejection Rapid ejection Volume of blood remain on ventricles after contraction PHOTO: Pressure-volume loop The vertical axis will represent changes in ventricular pressure. it is the period of rapid ejection. Point C – opening of SL valves.PHOTO: Relationship between left ventricular volume and intraventricular pressure during diastole and systole. Phase I – from 50 mL. the pressure is low – a little above 0 mmHg. the ventricular pressure still increases but the volume is already decreasing. net external work. RMT . the atrioventricular valves open. Phase I is ventricular filling. Also shown by the heavy red lines is the “volume -pressure diagram. There is closing of the AV valves so the first heart sound is heard. Phase IV – the volume of blood is still 50 mL but the pressure is decreasing and decreasing. the volume of blood in the ventricles increased to 120 or 130 mL but there is little increase in pressure. From C prime. Apolinario. the unit is mmHg. At point A. Point D – closing of the SL valves so the second heart sound is heard. that is the end diastolic volume. What are the factors outside the heart that may affect the cardiac output? 1. although the workload of the left ventricle is greater than that of the right ventricle. CO = SV x HR EDV – ESV Whatever factor that will affect EDV and ESV will also affect the SV. It is the EDV that will exert force on the ventricular wall stretching the ventricular wall before it contracts thus it is called preload or the load of the ventricle that is needed to be ejected. Stroke volume is equal to EDV minus ESV or ESV + SV will be the EDV. Stroke Volume (SV) is the amount/quantity/volume of blood ejected by each ventricle per contraction/per heartbeat/per cardiac cycle SV = EDV – ESV Normal Value: 70 mL The stroke volume of the left ventricle is the same of that of the right ventricle. On the other hand. Correlation of SV. the volume of blood increases in the ventricles with little increase in pressure. before contraction of the ventricle. that is now the end diastolic volume (EDV) which is a little less than 150 mL. The heart and the vascular system are actually inter-dependent and that is because of the close nature of the cardiovascular system. MD) Definition of Terms: Cardiac Output (CO) is the amount/quantity/volume of blood ejected by each ventricle per minute CO = SV x HR Normal Value: 5 L/min 5. From point A to point B. the ventricles will start to relax and the volume of blood that is now in the ventricles is the end systolic volume (ESV). So if the force of myocardial contraction increases. SV as a reflection of the force of myocardial contraction are factors intrinsic to the heart that will affect the cardiac output. if the force of myocardial contraction decreases. there will always be a certain amount of blood that will remain in the ventricles. But aside from factors intrinsic to the heart. End Systolic Volume (ESV) is the volume of blood in the ventricles at the end of systole Normal Value: 45-50 mL * ESV is the amount/quantity/volume of blood remaining in the ventricles after contraction. this is the ventricular filing time. RMT | . Total blood volume 2. End Diastolic Volume (EDV) What are the factors that will influence the EDV? EDV is the volume of blood in the ventricles after the relaxation phase. this is determined mainly by the force of myocardial contraction. Whatever factor that will affect the SV and HR will affect the CO. End Diastolic Volume (EDV) is the amount/quantity/volume of blood in the ventricles at the end of diastole. the atrioventricular (AV) valves will close so that whatever amount of blood will be present in the ventricles before closure of the AV valves. before contraction. but since all the valves are closed. From point B to C. the semilunar (SL) valves will close. the SV will increase. EDV. the heart rate and rhythm are determined by the activity of the SA node. PHOTO: Preload 1 Shannen Kaye B. before systole = PRELOAD Normal Value: 110-130 mL * Whatever amount of blood that will be present in the ventricles after the ventricular filling time. there are also factors outside the heart called peripheral factors that may also affect the cardiac output. As for the SV. Status of the arterial system which is the opposing force to ventricular contraction All of these factors make up the vascular or circulatory system so that means that the activity of the heart is dependent on the status of the vascular system and vice versa – the status of the vascular system is also dependent on the activity of the heart. No matter how strong the force of ventricular contraction is. Heart Rate (HR) the number of contractions/heart beats/cardiac cycles per minute Normal Value (normal resting adult): 75 beats per min. 000 mL/min * Although the left ventricle will pump blood against a higher pressure of resistance in the systemic circulation compared to the right ventricle. the SV will also decrease. At point A.Cardiodynamics (Gloria Marie M. although the left ventricular wall or musculature is thicker than that of the right ventricle. that is the period of ejection of blood from the ventricles so the EDV will be decreased and the amount that will be ejected is the stroke volume. the output of the two ventricles are the same. Apolinario. We can therefore say that the HR. * In a normally functioning heart. there will be no change in ventricular volume. the ventricles will now start to contract. ESV with the Ejection Loop From point D to point A. average of 130 mL. Status of the venous sytem that will deter blood back to the heart 3. Valerio. At point C. RMT | . that will now increase the force of myocardial contraction. the duration of cardiac cycle will decrease from 0.16 sec 0. there will be enough time for the ventricles to accommodate a larger volume of blood so the EDV increases.14 sec Filling time refers to the duration of the diastolic or relaxation phase because that is when the ventricles are filled with blood. the duration of one cardiac cycle is 0. the ventricles can still be filled with blood because from 60-180 beats per minute. there will be an increase in the frequency of depolarization on the sarcolemma of the cardiac muscle cell. that will now distend the ventricles. Effective filling pressure EFP = CVP – ITP EFP . more EDV. if the heart rate is 75 beats per minute. 2.80 sec Systole 0. Again. Based on the graph. The longer duration of the diastolic phase is important because it is during the diastole that the ventricles are filled with blood and at the same time. These black arrows represent the EDV. if the EDV is greater. it is during diastole that perfusion of oxygen supply to the cardiac muscle is better. Cardiac Cycle Duration with Heart Rate Duration Heart Rate 75 beats/min Cardiac cycle 0. What about the other equation? When the heart rate increases to 200 beats per minute. Which among the formula is true? In the formula. heart rate is directly related to CO. If the HR increases.pressure difference between the inside and outside of the heart.53 to 0. They are directly related because when the heart rate increases from 0-60.8 sec. HR FT EDV SV CO The reverse is also true that when the HR decreases. Effective filling time Both of the equations are true but there is a range of heart rate. Apolinario. The intra-thoracic pressure is always negative or below atmospheric pressure and that will enable the heart as well as the other dilatable structures in the thoracic cavity to be distended so it can accommodate greater volume. the duration of the systolic phase is 0.27 sec. FT EDV SV CO If the duration of filling time increases. And when the effective filling pressure is greater. the greater the EDV. and much longer is the duration of the diastolic phase which is 0. When the heart rate increases. the greater the ventricular wall is stretched. the greater the effective filling pressure. the more the ventricular wall is stretched. 2 Shannen Kaye B. If you will recall.30 sec 0. Factors Affecting EDV 1. That is how an increase in HR will increase the CO. that will now stretch the ventricular wall and if the ventricular wall is stretched. the greater the force that will be exerted on the ventricular wall. There is a range wherein the cardiac output will start to decrease with an increase in heart rate. Sympathetic stimulation increases not only the heart rate but also the force of contraction. another factor that may influence the diastolic volume is the effective filling pressure or transmural pressure . When the heart rate increases.8 to only 0. It is directed towards the ventricular wall so the greater the volume or EDV. the greater the force of contraction so the SV as well as the CO increases. The greater the difference between the pressure inside and outside of the heart. In the first phase. When the heart rate increases from 60-180 beats per minute. cardiac output increases. So EDV is directly related to cardiac output. stroke volume increases. the more Ca++ enters the cell and if more Ca++ enters the cell.14 sec which means that the filling time is really compromised and the EDV is severely decreased. there is a corresponding increase in cardiac output. SV and CO. the duration of the filling time will decrease – less time for ventricular filling so the EDV will decrease and so will the SV and CO. the stroke volume increases therefore the cardiac output increases. the duration of filling time is not yet compromised because the normal heart rate is 75 beats per minute so that means that the ventricles can still be filled with blood adequately so the cardiac output increases.27 sec Diastole 0. And sympathetic stimulation can no longer compensate on the very short duration of filling time. it is directly related and of course that is true. So the increase in heart rate is now less than the decrease in stroke volume so the cardiac output will now decrease.53 sec. And if the force of contraction is increases.Take note of where the black arrows are directed. the duration of the filling time will increase. All are directly directed. So the more the cardiac muscle is depolarized. the increase in heart rate is equal to the decrease in stroke volume so that the cardiac output is maintained at a constant level. the duration of the filling time is now severely compromised. When the heart rate increases from 180 beats per minute and above. the more the stroke volume increases. allowing the ventricles to accommodate a larger EDP.effective filling pressure CVP – central venous pressure ITP – intra-thoracic pressure Aside from the duration of the filling time. sympathetic stimulation increases the heart rate. If the force exerted on the ventricular wall is greater. the greater will be the force of contraction. So in other words. diastole is more affected (bigger decrease in duration of diastole) from 0. increased cardiac output. HR FT EDV SV CO One factor that will influence the duration of the filling time is heart rate. Pressure inside the heart is the central venous pressure while outside is the intra-thoracic pressure. when the heart rate increases from 0–60 beats per minute. the duration of the filling time is quite affected but still. Increased HR decreases the CO and decreased HR increases the CO but going back to the formula: CO = SV x HR. the greater the force of contraction.3 sec but if you will compare the decrease in the duration of systole and diastole. meaning to say that an increase in HR will increase the CO.53 sec Heart Rate 200 beats/min 0. The horizontal axis on the graph represents heart rate while the vertical axis represents cardiac output. arteries and veins . For example. So if the total blood volume increases. 1. Because of the closed nature of the cardiovascular system. there will be less overlapping between thin filaments and thick filaments so there will be less myosin length that will bind on the actin active site so when it contracts.their wall has a tone. The connective tissue on the cardiac muscle and on the pericardium prevents overdistention when the cardiac size increases because connective tissue is less distensible while the elastic tissue allows distension. If the venous wall is in a relaxed state. C=∆V ∆P Compliance is equal to change in volume over change in pressure. Increased pumping of skeletal muscle. If the force of contraction in the atria is greater. The veins are called capacitance vessels because the smooth muscle layer is thin and it has elastic tissue so the venous wall is highly distensible so it can accommodate large volume of blood. Since the force of myocardial contraction will affect the ESV. there is an additional amount of blood that will be ejected to the ventricles so the EDV increases. But during atrial systole.3. the change in volume should be higher or greater compared to the change in pressure. the greater will be the force exerted on ventricular wall. For a structure to have an increase in compliance. End Systolic Volume (ESV) What is the major factor that will affect the volume of blood remaining in the ventricles after contraction or ESV? It is the force of contraction. Increased total blood volume. Factors Affecting ESV a. the more the ventricular wall will be stretched and that will now increase the force of contraction and this is called heterometric autoregulation. Myocardial compliance All elastic structures have the property of compliance and that is the measure of distensibility or stretchability of an elastic structure. 4. there will be more than the 20% that will be added in the ventricular filing. RMT | . will be effectively ejected or pumped by the heart per minute so that means venous return is equal to cardiac output. and the cardiac muscle will not be The normal systolic volume (red line) is about 70 mL but if the force of myocardial contraction increases. what now are the factors that will influence the force of myocardial contraction? What is the EDV and the relationship between EDV and force of myocardial contraction is reflected in the Frank starling’s Law . the greater the EDV. One property of smooth muscle cells present in the vascular wall as well as in the visceral wall is the tone. Actin filament Myosin filament But remember that overstretching or overdistention of the cardiac muscle does not occur in the first place because of the presence of connective tissue. SV will increase. blood pools in the veins of the lower extremities. Force of myocardial contraction Frank Starling’s Law 3 Shannen Kaye B. there will be veno-constriction. remember that the ventricles can accommodate a large volume of blood with little increase in pressure and that is because of the presence of the elastic tissue in the cardiac muscle that will enable the ventricles to distend. Venous return VR = CO 5 L/min The most important factor that determines the EDV is the volume of blood returning to the heart per minute and that is venous return. whatever volume of blood that will return to heart per minute. Total blood volume is actually one factor that will affect venous return. EDV will decrease. So what is venous tone? Tone means state of partial contraction.000 mL per minute. if there is pooling of blood in the veins of the lower extremities. The average venous return is also 5 L or 5. So if the force of myocardial contraction increases. force of myocardial contraction is inversely related to the end systolic volume (ESV). In other words. Hetero . If the wall of the veins is partially contracted. the stomach and the small intestinal wall have a tone. Factors that affect cardiac muscle length: Stronger atrial contraction. Remember that most of the ventricular filling will take place when the ventricles as well as the atria are in a relaxed state. the venous return will decrease. the force of myocardial contraction will be determined by the initial muscle length that means resting length of the cardiac muscle or length of the cardiac muscle before it contracts. So again. The force of contraction will depend on the length of the cardiac muscle before it contracts so what will stretch the cardiac muscle before it contract ? The force that will be exerted by the EDV. ESV will increase. When you remain in a standing position for a long time. Autoregulation means that the heart itself can regulate its own force of contraction. ESV will decrease. it becomes weak. So the change in the length of cardiac muscle will enable the heart to regulate its own force of contraction. When the smooth muscle layer in the veins contract. the EDV will be more increased. SV will decrease. If the force of myocardial contraction decreases. EDV will also increase so that will stretch the ventricular wall. Apolinario. the same is also true with blood vessels. Increased venous tone. One property of smooth muscle is they can remain partially contracted for a long time. SV increases so the remaining part becomes smaller. Within physiologic limits. the blood cannot go back to the heart. venous return will increase. Metric is the length. there will be less capacity to accommodate blood so the blood will go back to the heart thus increasing venous return and EDV and that will stretch the cardiac muscle cell. There is a limit because when the cardiac muscle is overstretched or distended. And this is true for the ventricles. Remember that this only happens within physiologic limits – it does not stretch continuously when the EDV is increasing and more and more powerful the force contraction becomes. the blood in the veins cannot go back to the heart.changes. Ca++ will not return – it will remain bound to troponin C so there will still be muscle contraction. But once you move. Another action of cAMP-PK is to phosphorylate an intracellular protein called phospholamban. So another action of cAMP-PK is to phosphorylate troponin I so that troponin cannot bind with Ca++. But that is not the end of sympathetic effects. Venous return will then influence EDV. venous valves will open and blood will return to the heart. Activated G-proteins will activate the enzyme system adenylyl cylcase that will lead to the formation of an intracellular ligand or a second messenger that is cyclic AMP (cAMP). if any parasympathetic or vagal innervation to the ventricles. 4 Shannen Kaye B. sympathetic stimulation can also increase the heart rate so the more frequent the myocardial cell is depolarized. Remember that the coronary arteries supply blood and oxygen to the cardiac muscle itself. Relaxation(diastole) occurs as a result of uptake of Ca++ by the SR. the force of myocardial contraction will increase. there will be an area of that myocardium that will be deprived of oxygen supply so the area will be ischemic. So when the veins are compressed by skeletal muscle contraction. β-adrenergic receptor: cAMP-PK. mas madaming ca na papasok Another action of sympathetics is when norepinephrine and epinephrine bind with β1 receptors in the heart. Another important factor that will affect the force of myocardial contraction will be the amount Ca++ available that will bind with troponin C. The opening of the valves is directed toward the heart. PHOTO: Schematic diagram of the movement of calcium in excitation-contraction coupling in cardiac muscle. there are two sources of Ca++ for myocardial contraction: sarcoplasmic reticulum and ECF. this will cause activation of G-proteins. One action cAMP-PK is to phosphorylate the Ca++ channels on the sarcolemma. So if these factors will increase. So when there is an obstruction (e. In contrast. and parasympathetic that will release acetylcholine.g. Apolinario. The free cytosolic Ca++ activates contraction of the myofilaments (systole). βR. Influx of Ca++ from interstitial fluid during excitation triggers release of Ca++ form the sarcoplasmic reticulum (SR). But aside from this. If the Ca++ pump is inhibited. * The three factors: increased total blood volume. the skeletal muscle will contract and that will compress the veins. increased venous tone and increased pumping of the skeletal muscle will first influence venous return. and to a limited degree by the Ca++-ATPase pump. cAMP will mediate the actions of catecholamines on the cardiac muscle cell and one action of cAMP is to cause activation of another intracellular enzyme that is protein kinase A (cAMP-PK). Increased negative intrathoracic pressure. RMT | . the overall force of contraction will decrease and that will predispose to ventricular or heart failure. When it is phosphorylated. 2. more Ca++ will enter the cell. norepinephrine. again. But hidni dun nagtatapos ang sympathetic effects. Autonomics Aside from cardiac muscle length another factor that will influence the force of myocardial contraction is the autonomic innervations: sympathetic that will release catecholamine. the inhibitory effect of phospholamban will decrease so the Ca++ pump will be activated and when activated. 4. Hindi lang basta nagpapapasok ng ca kasi malimit magdepolarize. that will allow more Ca++ to enter that will increase the force of myocardial contraction. the depolarization of cardiac muscle will be more frequent and remember that with each depolarization. If the ischemic area is not corrected. As a second messenger. it will also facilitate relaxation of the cardiac muscle by the action of cAMP-PK. thrombus or embolus) in one of the branches of coronary arteries. that will open up the venous valves.stretched. EDV is the one that will exert force on the ventricular muscle to stretch the ventricular muscle. aside from increasing the force of myocardial contraction. But once phosphorylated by cAMPPK. Calcium All of these are factors will affect cardiac muscle length before contraction. epinephrine. It is mentioned earlier that when the heart rate increases. cardiac muscle length will increase before contraction so that during contraction. vagal or parasympathetic stimulation by releasing acetylcholine will decrease the force of atrial contraction. Since there is an area in the myocardium that is not contracting. it will actively transport Ca++ back to the sarcoplasmic reticulum so there will be no Ca++ that is attached to troponin and the muscle will relax. 3. the more Ca++ will enter the myocardial cell and that will increase the force of contraction. sympathetic stimulation can also facilitate relaxation of the cardiac muscle. That means that the plasma Ca++ level will have an effect on the force of myocardial contraction. so that will stretch the ventricular muscle. It has no direct effect on the force of ventricular contraction because there is very little. In contrast to the skeletal muscle. But take note that sympathetic stimulation will increase not only the force of contraction. Sympathetic stimulation will increase the force of contraction of both the atria and ventricles primarily because norepinephrine binds with β 1 receptors will increase membrane permeability to calcium allowing more Ca++ to enter myocardial cell and that will increase the force of contraction. If troponin cannot bind with Ca++. Heart rate The force of myocardial contraction can also be influenced by heart rate. Increased negative intrathoracic pressure allows the ventricles to distend. Adequate coronary flow Another factor is adequacy of the coronary arteries. The normal action of phospholamban is to inhibit the Ca++ pump on the sarcoplasmic reticulum. it will cause necrosis to the tissue developing an infarct and that infarcted area cannot contract anymore. 5. When the veins are compressed. by extrusion of intracellular Ca++ by the 3 Na+-1 Ca++ antiporter. So again. cAMP-dependent protein kinase. it allows more Ca++ to enter and that will increase the force of contraction. It does not allow Ca++ to always enter the cell because when it always depolarizes. the muscle will relax because troponintropomyosin complex will go back to cover the active site of actin due to absence of troponin-Ca++ complex. Neural reflexes. The most important factor. Aside from the neurotransmitters released by the autonomic nerves. When the ventricles contract. When the right atrial wall is stretched. it is the pressure in the aorta. not much resistance to right ventricular contraction unless there is pulmonary hypertension. heart rate can also be affected by several hormones one of which is cortisol . RMT | . Sympathetic nerves innervating the SA node and the effect of norepinephrine is to increase membrane permeability to Na+ and Ca++ that will make the SA node more excitable so the heart rate will increase. If the Na+-Ca++ pump is activated. when venous return increases. During exercise. Other hormones are T3 and T4 – thyroid hormones. 3 Na+ will go inside and Ca+ will go outside decreasing the concentration of Ca+ inside the cell and that is not ideal if there is congestive heart failure. Why in the aortic artery only and not in pulmonary artery? Because remember that there is low/no pressure area in the pulmonary circulation. This time. Apolinario. That’s why the pressure in the ventricles is increasing and increasing but because the opposing force is greater.corticosteroids from the adrenal cortex. The main purpose of giving cardiac glycosides is to increase the force of myocardial contraction. parasympathetic or vagal stimulation will make the SA node more permeable to K+ so that will hyperpolarize the SA node making it less excitable. Emotions like excitement and anxiety will also increase the heart rate partly because of increased sympathetic stimulation. These reflexes that regulate arterial blood pressure can also regulate heart rate. PHOTO: Afterload Remember the photo on preload. heart rate increases. the blood or EDV goes in the aorta so the direction is directed towards the aorta but the pressure in the aorta counteracts the EDV so when the pressure is greater on the aorte. If the Na-Ca pump is not activated. Excitement and anxiety. Cardiac glycosides Cardiac glycosides are given to patient suffering from congestive heart failure. Heart rate can also be influenced by neural reflexes that are centered on the medulla and that will include reflexes that actually regulate arterial blood pressure: the baroreceptor reflex and the chemoreceptor reflex. So what is the consequence of that? There is much left so in every venous return. stroke volume decreases. When the aortic pressure increases. the arrows are directed on the ventricular wall because the EDV exerts force on the ventricular wall to increase the force of contraction. EDV will have a hard time to go out. The effect of cortisol is to potentiate the effect of epinephrine so that means increased corticosteroids may increase the heart rate. Afterload Afterload is the aortic pressure load. what will happen in the EDV? There is much left but 5 Shannen Kaye B. When the muscle is relaxed. Hormones. Exercise. opposing force to left ventricular contraction. end systolic volume increases and this is shown on the photo below: 6. the Na-K pump is activated. So if the aortic pressure increases. the volume of blood in the right atrium will increase and that will stretch the right atrial wall where you have the SA node. there will be no increase concentration of Ca++ that will go out of the cell or Ca++ will remain inside the cell so the force of contraction is increased. Increased environmental temperature can also increase the heart rate. More of the resistance happens in the left ventricle because there is high pressure area in the arterial system. So when we say afterload. the SA node is stimulated and that will increase the heart rate. The normal stroke volume is still represented by the red line. Thyroid hormones directly stimulate the SA node so that one clinical manifestation of hyperthyroidism is tachycardia. So this Bainbridge reflex is sensitive to an increase in blood volume that will return to the right atrium. 7. It is needed for the Ca++ to remain inside the cell to have an increased force of contraction. On the other hand. heart rate increases for two reasons: increased metabolism and increased sympathetic stimulation. stroke volume is decreased and the end systolic volume is increased. So what the cardiac glycosides do is to inhibit the Na-K pump so there will be no concentration for Na+ and that will not activate the Na-Ca pump.Factors that influence or regulate heart rate: Autonomics. Not only environmental temperature but also body temperature so when there is fever. Na-K pump will extrude 3 Na+ in exchange for 2 K+ transported into the cell creating a concentration gradient for Na that will now activate the Na+Ca++ pump. the tendency of the ventricles is to increase its contraction because the pressure against it is stronger. decreasing the heart rate. Temperature. Bainbridge reflex. To summarize the factors that will determine the cardiac output. Since the SV is less. Cardiac Output Myocardial contractility 6 Afterload Shannen Kaye B. Because if the EF falls below what is normal. These are the major factors that will determine cardiac output Effects of Various Conditions on Cardiac Output Increase: Anxiety or excitement (50-100%) – partly because of sympathetic stimulation. myocardial infarction. it means that the SV is decreased and it is decreased because the ventricular contraction is weak. Factors outside the heart or peripheral/coupling factors will include the preload (factors that will affect EDV) and afterload or aortic pressure load. The pressure-volume loop for the left ventricle is depicted here. Exercise (up to 700%) – increased metabolism. the SV and cardiac output will still be diminished. Epinephrine Decrease: - Sitting or lying down from a standing position (20-30%) Rapid arrhythmias – heart rate of 200 beats per minute that will severely compromise the duration of the filling time so that will decrease the cardiac output. RMT | .even if there is less amount that goes out. Increase in blood flow increases venous return and increases cardiac output. so what will happen to the EDV? EDV will increase because there is much [blood] left and there was an additional amount added during the relaxation phase. Increased environmental temperature Pregnancy – due to increased blood volume that will increase venous return. cardiac valve diseases. sympathetic stimulation. In the steady state the output from both the right and left ventricles is the same. Determinants of Cardiac Output Cardiac factors: Heart rate Coupling factors: Preload The volume of blood that should be ejected per contraction should be 65-70% of 130 mL that is why the average stroke volume is 70 mL. less will still be ejected so that eventually there will be pulling of blood in the left ventricle and that will cause the left ventricle to dilate. Factors intrinsic to the heart will include the heart rate and the force of myocardial contraction. chronic hypertension all of these factors that will decrease the force of myocardial contraction. But even if the contraction is increased but there is persistent increase in aortic pressure. arrhythmias. Apolinario. When the EDV is increased. the left ventricle will dilate so the force contraction will decrease. No change Sleep Moderate change in environmental temperature 8. Increases in arterial pressure (increased afterload) decrease stroke volume and thus cardiac output (lower panel). the ventricular wall will be stretched. even if the ventricular pressure is greatly increased. If the aortic valve hardens. Blood will again accumulate in the left ventricle and eventually. In patients suspected of having congestive heart failure. there are factors intrinsic to the heart and there are factors outside the heart. Stenosis Ejection Fraction (EF) Percentage of the EDV is ejected by the left ventricle per contraction EF = SV x 100 EDV Normal value: 65-70% Another condition that will increase aortic pressure is stenotic aortic valve. The cardiac output is calculated as: Cardiac output = Heart rate x stroke volume where: stroke volume = end-diastolic volume – end systolic volume Increases in venous return (increased preload) increase the stroke volume and thus cardiac output. - PHOTO: Pressure-Volume Loop. Heart diseases – examples are congestive heart failure. its contraction will be increased. Eating (30%) – eating increases blood flow to the gastrointestinal tract. some will still go back to the heart. eventually the venous return will also be lessened because there is a decrease in the amount ejected so less will go back or return to the heart. Cardiac output is the volume of blood pumped by the heart each minute. one procedure that is requested is 2-D echocardiogram to determine the ejection fraction (EF). the heart compensates so the CO increases.Cardiac Index Cardiac output per square meter or body surface area Normal value: 3L/min/m2 of body surface area Another factor that may influence cardiac output is body surface area and the normal cardiac index is 3L/min/m2. he who seeks finds. congestive heart failure.g. the door will be opened. RMT | . during moderate to heavy exercise or during athletic activities that will involve endurance (e. Hypereffective heart happens if there is sympathetic stimulation and parasympathetic inhibition. they have a bigger body surface area so the CO and cardiac index is increased because what happens is that when there is increased need (bigger muscles) to be supplied with blood. It means that in the elderly where the physical activity is less. Apolinario.g. Hypereffective because the heart can pump blood a volume that is greater than what is normal. Compared to the athletes who have welldeveloped muscles. the skeletal muscles atrophy so the body surface area decreases and the cardiac output and cardiac index is decreased. the CO may be increased from 5L to 1315 L per minute and that is called a hypereffective heart. seek and you will find. “Ask and it will be given to you. knock and the door will be opened to you. marathon races). The opposite is a hypoeffective heart –the heart pumps blood that is less than normal and that is brought about by cardiac diseases (e. and to him who knocks. cardiac valvular diseases). For everyone who asks receives. Cardiac Reserve Maximum percentage that cardiac output can increase above normal (300-600%) In certain conditions.” -Matthew 7:7-8 GOD BLESS YOU 7 Shannen Kaye B. rapid arrhythmia. resistance to blood flow is highest in the arterioles so the arterioles are called resistance vessels. The capillary wall is thin and porous . Tunica intima Tunica media Tunica adventitia PHOTO: Schematic diagram of the parallel and series arrangement of the vessels composing the circulatory system. There are two functions of veins: one is to act as blood reservoir and another one is to return blood back to the heart. When the left ventricle contracts. On the left is the venous system or collecting vessels.it allows exchange of fluids and some solutes between intravascular and interstitial fluid compartments. 2. when blood is ejected to the aorta. 1 Shannen Kaye B. the wall of the different blood vessels is made up of the same structure. Take note that the blood vessels are not rigid tubes. On the right is the arterial system or distributing vessels. From the capillaries. Apolinario. Comparing the wall of the vein to that of an artery. blood will be collected by the venules which will then coalesce to form the bigger veins. RMT| Except for the capillaries. the venous wall is thinner and more distensible that is why the veins can accommodate a large volume of blood with little increase in pressure and the volume of blood that is contained in the veins is what we call unstressed blood volume because of the low pressure area of the venous system. that will now increase tremendously blood flow to the capillaries and to the tissues. The capillaries are known as exchange vessels.by transporting blood. among all the different types of blood vessels. MD) The Circulatory System or Vascular System is made up of different types of blood vessels that are arranged either parallel or in series with one another forming a closed system of conduits or tubes that will transport blood to and from the heart. It means that the vascular capacity is bigger and veins are also called capacitance vessels. Since the systemic circulation will supply blood to almost all organs of the body. it is also called peripheral or greater circulation. The middle layer is the tunica media which is made up of smooth muscle fibers. On the other hand. there are venous valves present with openings of which are directed towards the heart. Blood Vessels In the different organs of the body. the aortic and arterial wall will recoil on the contained blood. when the smooth muscle layer of the arteriolar wall relaxes or if there is vasodilatation. The primary function of the circulatory system is to service the needs of the tissues that is . On the other hand. The pulmonary circulation receives unoxygenated or venous blood from the right heart and supplies blood to the lungs. . So that when you move your limbs and the skeletal muscles contract that will open up the venous valves and facilitate venous return. the arteries will divide into smaller branches forming the arterioles. the wall of the arterioles contains more smooth muscle fibers than elastic tissue . blood is ejected to the aorta and from the aorta to the arteries. the systemic circulation receives arterial or oxygenated blood from the left heart and supplies blood to almost all organs of the body except for the lungs. during ventricular diastole. the circulatory system is divided into two – pulmonary and systemic circulation. Valerio. The innermost layer is the tunica intima which is made up of the endothelium and basement membrane. As what we have learned from the previous lecture. In the veins of the limbs or extremities. The crescent-shaped thickenings proximal to the capillary beds represent the arterioles (resistance vessels). So one important function of the arterioles is to regulate blood flow to the capillaries and to the tissues and also because of its thick muscular layer. it will transport essential substances like oxygen and nutrients to the tissues and at the same time it will transport the waste products of metabolism away from the tissues. they are distensible. So that will make the aortic and arterial wall highly distensible so during ventricular systole. One important characteristic of the aortic as well as arterial wall is that it contains more elastic tissue than smooth muscle fibers . the presence of connective tissue in the vascular wall will prevent overstretching or over distension of the vascular wall when blood volume as well as blood pressure increases. There are three layers of the vascular wall. that will decrease tremendously blood flow to the capillaries and to the tissues. This time. The wall of the aorta and arteries is strong and thick so it is able to transport oxygenated blood under high pressure to the different organs of the body and we call the blood volume that is contained in the arterial system as stressed blood volume . Just like in the heart. 3. Layers of the Blood Vessel 1. The capillary beds are represented by thin lines connecting the arteries (on the right) with the veins (on the left). On the other hand. the aortic wall will distend to accommodate the large volume of blood. In fact.Circulatory or Vascular System (Gloria Marie M. The smallest blood vessels are the capillaries. the arteriolar wall has the thickest muscular layer so that when the smooth muscle layer of the arteriolar wall contracts or if there is vasoconstriction. The outermost layer is the tunica adventitia which is made up of connective tissue. d. Local factors. Aside from neural. epinephrine has a greater effect than norepinephrine. The vascular smooth muscle cell is also surrounded by the sarcolemma and present on the sarcolemma are voltagegated as well as ligand-gated calcium channels. c. Stimuli. Few mitochondria. Another important property of the vascular smooth muscle . Contraction (or inhibition of contraction) of smooth muscles can be initiated by (1) the intrinsic activity of pacemaker cells. Remember in relation to beta-2 receptors. that will now stretch the arterial wall that will initiate a reflex action that will cause vasoconstriction. Sympathetic adrenergic nerves innervate the blood vessels in the skin and viscera while sympathetic cholinergic nerves innervate the blood vessels in the skeletal muscle. For example. 5. 2. Contractile Proteins. Stretch. Hormone concentrations depend on diffusion distance. Sarcoplasmic Reticulum. calcium will bind with another protein and that is calmodulin so you have a calcium-calmodulin complex that will initiate vascular smooth muscle contraction. There are fewer mitochondria in the smooth muscle and the main source of energy for contraction is glycolysis. So that the duration of the contraction-relaxation cycle in the vascular smooth muscle is also longer. PHOTO: Control systems of smooth muscle. myosin and tropomyosin but there is no troponin so in order to contract. It ranges from -50 to -60 mv. Remember that in the skeletal muscle. Single-unit smooth muscles are like cardiac muscle. In vascular smooth muscle. Tonic contraction. Resting Membrane Potential. The sarcoplasmic reticulum is less welldeveloped so that means it is not able to store large quantities of calcium ions just like in the cardiac muscle cell so in order to contract. First is again neural so we have autonomic innervation and the vascular smooth muscle is innervated mainly by the sympathetic nervous system so you have sympathetic adrenergic and sympathetic cholinergic. and electrical activity is propagated throughout the tissue. The action potential generated is brought mainly by opening of slow calcium channels so that will make the duration of the vascular smooth muscle action potential longer than that in the skeletal muscle. instead the invaginations will form cave-like 2 Shannen Kaye B. Neural. There are two types of smooth muscles in the body: multi-unit smooth muscle and single unit smooth muscle. The activity of the vascular smooth muscle is not regulated by the cerebral cortex. Compared to the skeletal muscle cell. 2 types of Smooth Muscle 1. B. You also have norepinephrine and epinephrine from the adrenal medulla so that when either norepinephrine or epinephrine binds with alpha-1 receptors that will cause contraction of the vascular smooth muscle so there will be vasoconstriction. Contractile proteins are also present that will include actin. when the blood volume and blood pressure increased. . Sarcolemma. Local factors for example actively metabolizing tissue so there will be oxygen consumption and production of carbon dioxide. Hormones. release. this calveolae are actually analogous to the T-tubules. Among the circulating vasoconstrictors are angiotensin 2 and vasopressin or antidiuretic hormone (ADH). Also present is a calcium pump. Apolinario. 9. In sympathetic cholinergic. and a sodiumcalcium anti-porter. Multiunit smooth muscles resemble striated muscles in that there is no electrical coupling and neural regulation is important. when either norepinephrine or epinephrine binds with beta-2 receptors. a sodium-potassium anti-porter. Stimuli that will cause contraction of the vascular smooth muscle. structures which are called calveolae. you have acetylcholine binding with muscarinic receptors that will also relax the vascular smooth muscle in the skeletal muscle so there will be vasodilatation. In the visceral wall as well as the vascular wall. RMT| 3. that will cause relaxation of the vascular smooth muscle so there will be vasodilatation. the type of smooth muscle fibers present is mostly the single unit type. You have an action potential for a somatic nerve transmitted to the skeletal muscle cell that will depolarize the skeletal muscle cell and that will now initiate the excitationcontraction coupling. uptake. these two factors will also cause vasodilatation. However. Characteristics of Smooth Muscle 1. there are different types of stimuli that can stimulate the vascular smooth muscle: a. the vascular smooth muscle can also be stimulated by circulating hormones which could either be vasoconstrictors or vasodilators. Smaller. or drug with specific receptors activates contraction by increasing cell Ca++. The combination of a neurotransmitter. pH = H+ 8.Properties and Characteristic of the Vascular Smooth Muscle 6. Also present on the membrane of the sarcoplasmic reticulum are ryanodine receptors that will bind with calcium coming from the ECF and there is also a calcium pump. The RMP is less negative. The neurotransmitter agent that is released by sympathetic nerves is norepinephrine. Multiunit Single unit 7. the primary stimulus will be neural or nervous. So that oxygen tension (pO 2) will decrease and pO2 pCO2 carbon dioxide tension (pCO 2) will increase. A. Most smooth muscles probably lie between the two ends of the single unit-multiunit spectrum. 2. or (3) circulating or locally generated hormones or signalling molecules. Stretch of the muscle will initiate a reflex action. the smooth muscle cell is smaller Involuntary. b. (2) neutrally released transmitters. On the other hand. The response of the cells depends on the concentration of the transmitters or hormones at the cell membrane and the nature of the receptors present. invaginations of the sarcolemma will not form the T-tubules. cells lacking close neuromuscular contacts will have a limited response to neural activity unless they are electrically coupled so that depolarization is transmitted from cell to cell. and catabolism. However. Among the circulating vasodilators are bradykinin and histamine. 4. hormone. Consequently. it is also unstable.it can remain partially contracted for a long time with little expenditure of energy and that is what we call tonic contraction. there has to be another source of calcium ions and that is the extracellular fluid (ECF). It will take some time before the muscle will relax by activation of another intracellular enzyme called myosin phosphatase. There are several factors that can either stimulate or inhibit the vascular smooth muscle. there are gap junctions present in the membrane allowing ions to flow freely from one muscle fiber to the next so that when an action potential is generated anywhere in a bundle. When activated. When activated. Ca++ pump on the sarcolemma or Ca++-Na+ antiporter. there is no Z line. With increased activity of ATPase. So that force generated in one muscle fiber can be transmitted to other muscle fibers as well. In the relaxed state. Apolinario. all of these will produce vasodilatation. In the skeletal muscle as well as in the cardiac muscle. Contraction-Relaxation Cycle Latch-Bridge Mechanism Repolarization Ca++ out Myosin phosphatase Dephosphorylation of myosin relax M+A On the other hand. Linkages consisting of specialized junctions or interstitial fibrillar material functionally couple the contractile apparatus of adjacent cells.Other local factors that will cause vasodilatation will include a decrease in plasma pH so increase hydrogen. and myofilaments in smooth muscle cells. alternating thick and thin filaments and alternating light and dark bands will not be seen. the vascular smooth muscle will remain contracted that is why it is capable of tonic contraction with little expenditure of energy. 3 Shannen Kaye B. When myosin is dephosphorylated. Note that cross-bridge phosphorylation at a specific site on a myosin regulatory light chain requires ATP in addition to that used in each cyclic interaction with actin. it can be transmitted readily and that will cause the whole bundle to depolarize and to contract as a single unit and that arrangement of the muscle fiber is called synctitium. with repolarization. Smooth Muscle Fiber PHOTO: Regulation of smooth muscle myosin interactions with actin by Ca++stimulated phosphorylation. Smooth muscle is non-striated. there are dense bodies attached to the membrane of the smooth muscle which will also provide an attachment between the membrane of the individual muscle fibers. myosin will now form cross bridges with actin and that will bring about contraction. RMT| . That is why the type of the smooth muscle is singleunit smooth muscle. myosin light chain kinase will cause phosphorylation of myosin which will then increase the activity of ATPase. Phosphorylated cross-bridges cycle until they are dephosphorylated by myosin phosphatase. When the Ca++ enters. instead of the Z line. that will allow Ca++ to enter the vascular smooth muscle cell. Another characteristic. once Ca++ is unbound from troponin. it is expected to relax but in this case. If the membrane is depolarized. What happens is that the calcium-calmodulin complex will activate an intracellular enzyme that is myosin light chain kinase. increase adenosine. it will bind with calmodulin which will now initiate the contraction process. Increase potassium. even if Ca++ is removed from calmodulin. it will be unbound from actin and that will bring about relaxation and this is called the latch-bridge mechanism. Ca++ will be removed either through the activity of the Ca++ pump on the sarcoplasmic reticulum. Depolarization Ca + calmodulin Myosin light-chain kinase Phosphorylation of myosin Increased ATPase M+A contraction PHOTO: Apparent organization of cell-to-cell contacts. There is no regular arrangement of the actin and myosin filaments so that when you observe the smooth muscle under the microscope. The structure of a smooth muscle fiber is usually arranged in bundles. myosin phosphatase will cause dephosphorylation of myosin. Small contractile elements functionally equivalent to a sarcomere underlie the similarities in mechanisms between smooth and skeletal muscle. Also. cross-bridges are present as highenergy myosin-ADP-Pi complex in the presence of ATP. increase lactic acid concentration. Attachment to actin depends on phosphorylation of the cross-bridge by a Ca++-calmodulin-dependent myosin-lightchain kinase (MLCK). cytoskeleton. collagen.you put the blood vessels side by side then spread it.6 Let us now differentiate the blood vessels that make up the circulatory system so you have the aorta.002 + 1. The aorta which has a small cross-sectional area has the highest velocity of blood flow. in contrast. LA. So to summarize. wall thickness. and relative amounts of the principal components of the vessel walls of the various blood vessels that compose the circulatory system. it has the biggest cross-sectional area.000 0. large arteries. . Correlate it with the velocity of the blood flow. that is not the size of the blood vessel .02 + 0. Composition of the vascular wall you have elastin. you will notice that although the aorta is the biggest artery in the body. 2 vena cava – superior and inferior. the capillaries with the biggest cross sectional area has the lowest velocity of blood flow. Differentiation of the Blood Vessels Char. and the maximal cross-sectional area and minimal flow rate in the capillaries. that is the distance travelled by a volume of blood per unit of time.010 1010 5.004 3 x 108 4. It is mentioned earlier that the arterial system is a high pressure area while the venous system is a low pressure area. pressure is high in the arterial system. venules and vena cava. What does cross-sectional area mean? If you put the blood vessels side by side. the vena cava actually has a bigger radius than the aorta but the aorta has the thickest wall. RMT| PHOTO: Phasic pressure.5 12 109 300 0. Number in body Crosssectional area Radius (mm) Wall thickness (microns) Elastin Smooth muscle Collagen Trasmural pressure (mmHg) Peak velocity (cm/s) Aorta Arteriole Capillary Venules Vena cava 2 capillaries which is slower because it is numerous and smaller and that is why the velocity is inversely related to the cross-sectional area. millions of venules. its cross-sectional area is small. capillaries. For the velocity of blood flow. which among those blood vessels would occupy the most space. 1 4. Elastin and collagen component is highest in the aorta but take note the smooth muscle component is most abundant in arterioles. cross-sectional area is inversely related to velocity. cross-sectional area increases from the aorta to the capillaries. the major pressure drop across the small arteries and arterioles. When we say velocity of blood flow. lowest in the vena cava. So if blood flow is 5L/min. it is slower to fill up the 5L so although the volume is the same in both. When we say cross-sectional area. CAP. capillaries. there is one aorta. this is difference in the pressure between the inside and outside of a blood vessel and the transmural pressure is highest in the aorta. which among the blood vessels will occupy the biggest space and of course that will be the most numerous even though it is the smallest and that will be the capillaries. As to pressure. arterioles. 50 0. again. and cross-sectional area of the systemic circulation. small veins. The capillary wall has no elastin. VC. velocity of flow. and no collagen. in a big blood vessel like the aorta. the blood flow in the aorta is faster compared to the 4 Shannen Kaye B. it decreases from the capillaries to the vena cava. two vena cava and billions of capillaries and if you spread all of those.3 0. SA.5 + ++ +++ 110 +++ + 70 0 0 20 + + 10 ++ + 5 PHOTO: Internal diameter. Why did that happen? You will learn later on that again because of the closed nature of the circulatory system. Apolinario. Compare it to the smallest blood vessel in the body which is the capillary.017 0. large veins. and billions of capillaries.02 4. AO. that means myosin can pull the actin filament on one side in one direction at the same time pulling the other actin filament on the other side in the opposite direction. ART. blood flow is equal to cardiac output equal to venous return so that means the blood flow in every blood vessel per unit of time is the same. As for transmural pressure.000 0. The important features are the inverse relationship between velocity and cross-sectional area. venules. When activated. aorta. millions of arterioles.02 18 17 2 +++ 0. it can easily fill up 5 L. What about the capillaries? It is small and numerous.Attached to the dense bodies are the actin filaments and interspersed within the actin filaments are the myosin filaments. it increases from the capillaries to the vena cava. As to cross-sectional area. As to radius. This graph will show you again the relationship between crosssectional area and velocity of blood flow. it is highest in the aorta so it decreases from the aorta to the capillaries. no smooth muscle. SV. highest in the aorta and then it progressively decreases towards the vena cava but the biggest drop in pressure is in the arterioles. And the myosin filaments here form what we call side-polar crossbridges – myosin on one side is attached to actin and it is attached to actin on the other side. LV.001 0 0. Cross sections of the vessels are not drawn to scale because of the huge range from the aorta and venae cavae to capillary. arterioles. VEN. Number in the body: there is only 1 aorta. As you can see. venae cavae. smooth muscle. small arteries. that is the distance that is travelled by a volume of blood in a blood vessel. about 65% of the blood is contained in the venous system. whose wall is thin and also distensible so the same volume of blood will exert less force or pressure to distend the venous wall. it can accommodate a large volume of blood with little increase in pressure. RMT| Where: .Velocity V=D T The formula for velocity is distance over time and the unit is centimetres per second. increase in volume but there is only little increase in pressure. artery or vein? It is supposed to be the artery but the arteries are 8x less distensible than the veins. 13% in the arteries. How come that the venous system can accommodate large volume of blood with little increase in pressure? When we say compliance or vascular capacity or capacitance. But when you say blood flow that is the volume/quantity/amount of blood that will pass through a blood vessel per unit of time (unit: mL/unit of time). Veins = increase V little P Arteries = increase V higher P In the case of the veins. it is more distensible. So the venous wall being thinner that also has elastic tissue. that is the measure of the degree of stretching or distensibility of an elastic structure. So the compliance is higher in veins. velocity is also increased. Distribution of Blood Volume PHOTO: Distribution of blood (in percentage of total blood) in the different parts of the circulatory system. the two are directly related. So a structure can be distensible because of the presence of elastic tissue and compliance is equal to change in volume over change in pressure or how much blood can be accommodated in a blood vessel for every mmHg increase in pressure. it can accommodate a large volume of blood compared to the artery. Which is more distensible. same volume and increase in pressure. We already explained why velocity is inversely related to crosssectional area. 5% in the capillaries. Meaning to say. What is the difference between velocity and blood flow because the two are directly related? Velocity is equal to blood flow over cross-sectional area. As said earlier. In the arteries. There are more elastic tissue in the arterial wall than in the venous wall but the venous wall is thinner. The two are directly related so if the blood flow is increased. artery or vein? Arteries have more elastic tissue and the elastic tissue is responsible for the distensibility of a blood vessel. a given increase in pressure causes about 8x as much increase in blood in a vein as in on artery of comparable size. When you say velocity. again.e. Compare it to the same volume of blood in the vein. if you have an artery and a vein of the same size. And again. 7% in the heart and 9% in the pulmonary circulation. Apolinario. So how did that happen? The artery has more elastic tissue so we expect it to be more distensible than the vein but how come that it is 8x less distensible? The veins has higher vascular capacity. Vascular Compliance or Capacitance C=ΔV ΔP Δ V = change in volume Δ P = change in pressure 5 Shannen Kaye B. Arteries are 8x less distensible than the veins i. V=Q X Where: Q = blood flow X = area How much quantity of blood that can be stored in a given portion the circulation for each millimeter of mercury pressure rise. that volume of blood will exert a greater pressure or force. when we say velocity. Vascular Distensibility Which of the two will have more elastic tissue. 2% in the arterioles. both can accommodate the same volume of blood but in order to stretch the arterial wall which is thick and strong. Percentage 39 % 25 % 8% 5% 2% 5% 7% 9% Parts of circulatory system Large veins Small veins and venules Large arteries Small arteries Arterioles Capillaries Heart Pulmonary circulation At any point in a cardiac cycle. that is the distance that a volume of blood will travel per unit of time in a blood vessel (unit: cm/s). Tension is tension on the wall and pressure is inside a blood vessel. So that means that when the blood . there has to be difference in pressure between point A and point B. you have a rigid aorta or artery. it can now recoil on the contained blood. the greater the difference in pressure. it can no longer recoil. C . and T = wall tension as the force per unit length tangenital to the vessel wall. the greater will be the blood flow so that if the pressure in point A is equal to that in point B. and vein because no blood will flow. its wall is strong. And because of the recoil of the aortic wall.PHOTO: A to D. If the arteriole will constrict.e. capillaries and to the tissues so that means although the ejection of blood from the ventricles to the arterial system is pulsatile. but flow ceases during diastole. That is why the capillary wall is not prone to rupture. . Ohms Law Volume flow = Δ Pressure Resistance According to Ohms law. For example. wall tension acts to prevent rupture along a theoretical longitudinal slit in the vessel. to the arterioles.e. blood flows through the capillaries during systole. that is the impediment to blood flow and there are two types of resistance depending on the arrangement of the blood vessels. As for resistance. capillaries and to the tissues but as you can see here. Below. there is less tension on the wall so that means less pressure is needed to balance the tension on the wall so its transmural pressure is also less. because the walls are already rigid. So for blood to flow from point A to point B. B . blood will be ejected to the aorta so that the volume of blood in the aorta will increase and under normal conditions. during ventricular systole. the aortic wall will distend. capillaries and therefore to the tissues. A . let’s say you have an artery connected to an arteriole. Compare it to a large artery. When the arteries are normally compliant. . blood will be ejected to the aorta.What will happen if the arterial wall becomes rigid for example there is atherosclerosis which is common in the elderly. where P = intraluminal pressure. is a normal artery or aorta. artery or aorta is more prone to rupture. capillaries and tissues so that means if the arterial wall becomes rigid i. Still we are discussing compliance or stretchability of the arterial or aortic wall. When the arteries are rigid. venules. It is equal to cardiac output and venous return so that means the average blood flow is 5. T resistance P P = distending pressure T = wall tension T 6 Shannen Kaye B. r = radius of the vessel. Apolinario. there are blood vessels arranged in series or arranged in parallel with one another. blood flows through the capillaries throughout the cardiac cycle. So that will make the arterial wall less distensible. the aortic wall being distensible.000 mL or 5L/min.So that during ventricular diastole. So they are directly related. that volume of blood will be transported under high pressure to the arteries. connected to a capillary and then you have a venule and finally a vein. it becomes stagnant.During ventricular systole. How come a small blood vessel like a capillary is less prone to rupture while in large vessel i. that will already compromise blood supply to the tissues during ventricular diastole. Series: artery arteriole capillary venule vein TR = Laplace equation that is wall tension is equal to the product of distending pressure and radius of a blood vessel. At the top. RMT| In in series arrangement. there will be no blood flow. arterioles. At the same time. the transport of blood to the tissues is continuous so there is still transport of blood to the tissues during diastole. it can still be transported under high pressure to the arteries. D . arterioles. During ventricular systole. blood flow is equal to pressure gradient over resistance. arterioles. during ventricular diastole (ventricles are not ejecting). so the wall tension is high so that the pressure needed to balance the wall tension is also high so that will make the transmural pressure high also that is why a large blood vessel like an artery or aorta is more prone to rupture. it is not distended anymore. A B PHOTO: Diagram of a small blood vessel to illustrate the law of Laplace: T = Pr. Nothing will push the blood towards the arteries.Now. that will still push blood to the arteries. resistance to blood flow will increase and so will resistance in the capillaries. Laplace equation Large artery Capillary In the case of the capillary. T=Pr Where: T = tension on the wall P = transmural pressure (pressure inside blood vessel) r = radius of the vessel Let’s say this (above) is a blood vessel with point A and point B. atherosclerosis. Blood Flow Volume of blood that passes through a specific point in the circulatory system per minute Approximately equal to CO and VR Blood flow is the amount/quantity/volume of blood that will pass through a specific point in the circulatory minute per minute. increase RBC count. That means the highest velocity will be at the center and that will be the direction. In polycythemic patients. Another important factor related to resistance but this time inversely related is the radius of a blood vessel and not just the radius. If there is an obstruction. that will make the endothelial lining rough and when blood passes over a rough surface. decrease RBC count. or if during vasodilatation. If the velocity of blood flow increases. On the other hand. Apolinario. radius to the 4th so that will make it a very important factor. The longer the blood vessel is. during vasoconstriction. the abnormal sound is a murmur. Turbulent Flow When blood flows in different directions. when the blood reaches the end of the blood vessel it cannot be that the one in contact with the blood vessel wall will have the highest velocity and the one at the center will have the lowest velocity. in the blood vessel it is called a bruit.vessels are arranged in series.000 mL/min PHOTO: When flow is laminar. an artery will give rise to several arterioles arranged in parallel with one another. the total resistance is equal to the sum of all the resistances in individual blood vessels. the fluid does not move in a radial or circumferential direction. Meaning to say. it creates a sound and that is what we call a turbulent flow and the sound that is produced by turbulent flow is a bruit.000. 2. the fluid that moves along the central axis of the tube has the maximal velocity. The layer of fluid in contact with the wall is motionless. Between 2. So resistance is directly related to length of a blood vessel. the lumen or the radius of a blood vessel will increase twice its normal size. there is increase RBC production. What are the conditions that will predispose to a turbulent type of blood flow? 1. If the blood passes over a rough surface. The sum of all the resistances to blood flow in the systemic or peripheral circulation is what we call total peripheral resistance (TPR). that will again predispose to a turbulent type of blood flow. RMT| . blood flows laminar then suddenly there is a thrombus. that means blood flow will increase 4x normal. Reynold’s Number Re = Diameter x Velocity x Density Viscosity The factors that will increase the tendency of blood flow to become turbulent are expressed in Reynold’s number. It also related to blood viscosity. blood flow is laminar and there is very little turbulence but it will easily die out. The next layer will move at a higher velocity. The direction is straight at a constant rate so that laminar flow is also called stream line and this type of blood flow is silent. In the heart. that will be the rate along a blood vessel meaning to say. Remember that blood is 3-4x more viscous than water and there are two factors that make blood viscous: haematocrit/concentration of red blood cells and concentration of plasma proteins. that will again change the direction and the rate of blood flow will be disturbed When the blood vessel makes a sharp angle. So the radius of the blood vessel is very important in regulating resistance to blood flow. if the lumen of a blood vessel will decrease twice its normal size. 2. the opposite is true to anaemic patients. Parallel: resistance TR < On the other hand. Remember that endothelial lining of a blood vessel is smooth. Each arteriole can function independently of the others so that if one arteriole will constrict. So along a blood vessel. the layer of blood that is in close contact with the vascular wall hardly moves. it creates no sound. the direction of blood flow is disturbed. 7 Shannen Kaye B. decrease haematocrit that will make blood less viscous so that the rate of blood flow increases. 3. But if there will an injury on the blood vessel wall or if there will be atherosclerotic plaques deposited on the blood vessel wall.000 to 3000 is the transition from laminar to turbulent flow but above 3000. all elements of the fluid move in streamlines that are parallel to the axis of the tube. The next layer which is a little farther away from the vascular wall will flow at a low velocity. and density of the fluid or medium whereas blood viscosity is inversely related to the Reynol d’s number. velocity of blood flow. increase haematocrit that will make blood more viscous so resistance to blood flow is increased. blood flow is definitely turbulent 0 1 Velocity 2 Venous Return Volume of blood that goes back to the heart per minute 5. the resistance will increase only in this (arrow) arteriole so the total resistance this time will become less than the resistance in one blood vessel. When will turbulent flow occur? If the Reynold’s number is below 2. The factors that are directly related to the Reynold’s number are diameter of blood vessel. that means blood flow will decrease 4x. 4. the higher the resistance to blood flow. Laminar Flow One type of blood flow is laminar flow wherein blood flows at a constant rate. Factors that will increase resistance to blood flow: Poiseuille’s Equation Resistance = Length x Viscosity x 8 Π r4 Factors that will increase resistance to blood flow are expressed in Poiseuille’s equation. When we say laminar flow. 2 Types of Blood Flow 1. abdominal pressure increases because for example during pregnancy or if there is tumor in the abdominal cavity or if there is ascites (accumulation of fluid in the abdominal cavity). Why will pressure in the aorta decease during ventricular diastole? Because there is no more ejection of blood from the ventricles and the volume of blood that is present in the aorta will drop off to the arteries. When the rate of venous return increases above normal so that will easily fill up the right atrium so that is increased volume blood in the right atrium will increase the CVP. Venous return is equal to mean circulatory static filling pressure (MCSFP) – the measure of the degree of filling of the systemic or circulatory system. when blood blow in the systemic circulation stops the pressure exerted by the volume of blood in the systemic circulation is what we call MCSFP – how much blood is present in the systemic circulation when blood flow stops. Factors that Regulate Venous Return VR = MCSFP – CVP RV Where: MCSFP = Mean Circulatory Static Filling Pressure CVP = Central Venous Pressure RV = resistance in veins 5. It is equal to cardiac output and equal to blood flow so it is 5. The other factor is the pumping ability of the heart. What will happen when the venous valves are damaged? When you stand for a 8 Shannen Kaye B. arterioles. the volume of blood in the right atrium will be ejected to the right ventricle and on to the pulmonary circulation. Diastolic Pressure (DP) = is the lowest pressure in the aorta at diastole Diastolic pressure is the lowest pressure recorded in the aorta during ventricular diastole. the volume of blood in the aorta will increase and that will exert pressure on the aortic wall to distend the aortic wall. Negative intra-thoracic pressure. 140 and the average is 120 mmHg) because of atherosclerosis that will cause hardening of the aortic wall so the volume of blood ejected by the left ventricle will have to exert a greater force to stretch the already rigid aortic wall. the venous valves will open and that will facilitate venous return. in the elderly. Next is resistance in the veins which is quite low because remember that the veins are low pressure area but resistance may increase if the intra. CVP is central venous pressure or more specifically pressure in the right atrium which is normally 0 mmHg. When will the right atrial pressure or CVP increase? There are factors: 1. sympathetic stimulation increase venous tone. So. Where: So increase in the total blood volume will increase the MCSFP and therefore increase the venous return but it is inversely related to vascular capacity. MCSFP = TBV VC TBV = total blood volume VC = vascular capacity Arterial Blood Pressure Force exerted by the volume of blood on the arterial wall When you get your BP: 120/80. We all know that when you move your limbs. What if there is right-sided heart failure? So the pumping ability of the right heart is depressed so the blood in the right atrium will back up in the venous system and that will now increase the venous pressure so that one clinical manifestation of right-sided heart failure will be distension of the neck veins. what does that mean? What do you mean by arterial blood pressure? That is the force exerted by the volume of blood on the arterial wall. Venous pump. It is actually directly related to the total blood volume (TBV).000 mL or 5L/min. you increase the tone of the venous wall that will now increase the veins vascular capacity and therefore increase venous return. Since the venous return cannot be facilitated because of the damaged venous valves. CVP should be lower than the pressure in the venous system. Rate of venous return increases. Remember there is increase capacitance if the venous wall is in a relaxed state because the veins will accommodate a large volume of blood and that blood will not return to the heart so with sympathetic stimulation. 3. Apolinario. Meaning to say. 4. Pulse Pressure = SP – DP Where: SP = systolic pressure DP = diastolic pressure . Resistance in veins. that will now compress the veins so the resistance in the veins will increase and that will decrease venous return. diastolic. If the pumping ability of the heart is normal. Mean arterial pressure (Pa) represents the area under the arterial pressure curve. decrease vascular capacity. Why will the pressure in the aorta increase during ventricular systole? Because when blood is ejected into the aorta. It is expressed as systolic pressure over diastolic pressure. Pumping capacity of heart. systolic pressure is usually high (higher than normal – 130. long time. capillaries and tissues and the aortic wall will recoil. RMT| 2. Blood Pressure: Systolic Pressure (SP) = is the highest pressure in the aorta at systole Systolic pressure is the highest pressure recorded in the aorta during ventricular systole. and increase venous return. the accumulation of blood in the lower extremities will now cause stretching or distension on the wall of the veins and that will cause varicosities. For venous return to increase.Venous return is the amount/quantity/volume of blood that will return to the heart per minute. A negative intra-thoracic pressure that will allow the veins and the heart to dilate so that will facilitate venous return and allow more blood to be accommodated in the heart. and mean pressure. there will be pulling of blood on the lower extremities. Other factors that may influence venous return will be the venous pump or activity of the venous valves. PHOTO: Arterial systolic. pulse. The difference between the systolic pressure and diastolic pressure is the pulse pressure. With a decrease in TPR. and increase the cardiac output. 3. the systolic pressure increases. So hyperthyroid patients are prone to what we call high cardiac output failure. the volume of blood is still high and that will increase the diastolic pressure. Remember that during diastole. to the tissues etc. supposed to be there is peripheral run off blood to decrease the volume of blood in the aorta and the aortic wall will recoil. The pulse pressure can actually be influenced by two factors: one is stroke volume – greater stroke volume. The average pressure in the circulatory system in one cardiac system is the mean arterial pressure (MAP). RMT| . Blood volume. so there will be pulling of blood in the arterial system so that when the arterial wall “Trust in the Lord with all your heart and lean not on your own understanding. and he will make your paths straight. increase systolic pressure. no change in diastolic pressure so that will widen the pulse pressure. decrease diastolic pressure. and increase blood pressure. Another condition is in hyperthyroidism. its compliance will decrease and that will again increase the systolic pressure. diastolic pressure decreases so that will widen the pulse pressure. increase the stroke volume. The effect of an increased venous return on the heart increases the following parameters: end diastolic volume that will stretch the ventricular wall. MCSFP will increase venous return. CO increases. there is hypertension or if there is hypovolemia. the diastolic pressure will not change so that will now increase the pulse pressure. vasodilatation. When the compliance of the arteries decreases. here are the factors that affect the arterial blood pressure: 1. Compliance of arteries. when the arterial wall becomes rigid. Increase heat production will cause vasodilatation decreasing the total peripheral resistance (TPR). that will increase initially the MCSFP. Again. in the elderly with atherosclerosis. So in hyperthyroidism. So again. And it is equal to the diastolic pressure plus one third of the pulse pressure. Apolinario. no change in diastolic pressure so that will increase the pulse pressure. with increased metabolism. blood cannot runoff to the capillaries. Cardiac output. decrease diastolic pressure that will widen or increase the pulse pressure. Vasoconstriction that will increase TPR will increase mainly diastolic pressure. 4. if the TPR increases. what will happen to the pulse pressure? It will increase because the systolic pressure. This is the average pressure in the circulatory in one cardiac cycle.” -Proverbs 3:5-6 GOD BLESS YOU 9 Shannen Kaye B. When increased. The other factor is compliance of the arteries. thyroid hormones can increase intracellular metabolism. How come we always say that if there is hypervolemia. Why diastolic pressure? Because 60% of the cardiac cycle is diastole. increase cardiac output. But at the same time. only 40% is systole. increase force of contraction. you have an increase systolic pressure. What happens to the diastolic pressure? During exercise. When the cardiac output increases. which will be affected more? It is diastolic pressure but why? What causes an increase in TPR? Vasoconstriction. that will increase heat production. Now. in all your ways acknowledge him. Again. What if there is vasoconstriction? Increase TPR. there is increase heat production. Mean Arterial Pressure (MAP) MAP = DP + 1/3 (SP-DP) Where: MAP = mean arterial pressure DP = diastolic pressure SP-DP = pulse pressure recoils. Remember that this is not the average of systolic and diastolic pressure. there is hypotension? If blood volume increases. Factors that Affect ABP To summarize. increase stroke volume. increase cardiac output. it increases mainly systolic pressure. increase volume of blood in the aorta that will exert a greater force on the aortic wall. Increase in cardiac output will increase mainly systolic pressure. decrease TPR. will it be the systolic pressure or diastolic pressure? Systolic pressure because if the stroke volume increases. 2. If for example TPR is normal. Thyroid hormones can directly stimulate the SA node and the myocardial cell so increase heart rate. increase systolic pressure. increase stroke volume. increase CO. ABP = CO x TPR Where: ABP = arterial blood pressure CO = cardiac output TPR = total peripheral resistance The formula for arterial blood pressure (ABP) is cardiac output (CO) times total peripheral resistance. What about during moderate to heavy exercise? The sympathetic nervous system is stimulated so that will increase the heart rate. Total peripheral resistance. which will be affected more.