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.

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

Nodal His (NH) zone most distal, connects with the bundle of His

Purkinie system/ventricular conduction system = made up of bundle of HIS and purkinje fibers o Bundle of HIS located at the interventricular septum. The bundle of HIS forms right and left bundle branches. The left bundle branch will divide to form the posterior and anterior fascicles. 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.

0 4

-90 mv

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. Since there are many potassium leak channels on the membrane of the skeletal muscle and there is a concentration gradient for potassium, the tendency is for potassium to move out decreasing the amount of positively charged ions inside. Also present inside the cell are negatively charged molecules including proteins which are large molecules so they remain inside. The main extracellular cation is sodium, 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. The membrane is permeable to chloride at rest, it allows the chloride ions to move in but because of the presence of the negatively charged ions inside the cell, chloride will eventually get out. To maintain the concentration of Na and K inside the cell, you have the activity Na-K pump (3 Na out, 2 K in). These things stabilize the RMP of the cell to -90mv.
PHOTO: The cardiac conduction system

All of these cells are automatic cells and can generate own action potential. But in a normally functioning heart, 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. They are called latent pacemakers because although they do not normally generate action potential, in some abnormal conditions, they can be stimulated to generate their own action potential. The primary pacemaker of heart is the one that determines the heart rate number of heart beats per minute. The average heart beats per minute is 75-80 beats per minute. The SA node is the primary pacemaker of the heart because it is the fastest that can generate an action potential. 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 SA node will fire at a high rate of 75-80 beats per minute with each action potential that will depolarize other automatic cells. With each depolarization, 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. The Na-K pump will extrude sodium ions. The more frequent the other automatic cells are depolarized, the more sodium ions will enter the cell, the more Na-K pump will be activated, the more sodium ions will be extruded from the cell that would cause the cell to be hyperpolarized. If the other automatic cells are hyperpolarized, they will become less excitable. When the overdrive stops, the activity of Na-K pump will not stop immediately; it will remain active, continuing to extrude sodium ions, the more the other automatic cells will become hyperpolarized, the more they will become less excitable, and the more their automaticity will be diminished. (44m) 2. Non-automatic cells Non-automatic cells cannot generate own AP and are specialized mainly for contraction. The presence of non-automatic cells in the heart, even if you cut the automatic innervation to the cardiac muscle, it can still contract. Non-automatic cells are the cardiac muscle cells present in the atrial wall and ventricular wall.

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 more potassium leak channels present on the membrane, more K+ will move out of the cell, making the membrane potential more negative and vice versa. Phase O depolarization opening of fast voltage gated Na+ channels Phase 1,2,3 repolarization re-establishing the RMP, brought about by the closure of fast voltage gated Na channels and opening of slow voltage gated K channels. Since these K channels are slow, they remain open for a long time allowing K+ to continuously move out so that at some point, the MP will go below the resting level = hyperpolarization. When the K+ gated are closed, the RMP will be restored Automatic Fiber Action Potential 1

4 Properties of Myocardial Cells 1st Property: Automaticity generation of action potentials 4 Shannen Kaye B. Apolinario, RMT -60 mv

250-300 milliseconds hyperpolarization Action potential of an automatic cell- SA node

Difference from the AP of skeletal muscle: Duration is longer 250-300 millisecond RMP is less negative - -60 mv Phase 4 slow rise in membrane potential and is unstable. The slow rise in membrane potential is called the pre-potential or slow diastolic depolarization. There is more Na leak channels, membrane potential increases. Phase 0 Depolarization. Somewhat inclined, depolarization occurs slowly Phase 1,2,3 Repolarization. Inclined, occurs slowly, 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. Voltage gated K channels will open allowing K efflux. But repolarization cannot occur rapidly because of the long lasting Ca channels are still open. Ca influx and K efflux Midway of repo: Ca channels close, K channels open Na leakage, Decrease K -40 mv -50 mv -60 mv 250-300 milliseconds Action potential of an automatic cell (same thing happens in SA node, AV node, bundle of HIS) With parasympathetic or vagal stimulation, the neurotransmitter released (NTA) released is acetylcholine (Ache). When Ache binds with muscarinic 2 receptors in the SA node, it increases permeability to K+, allowing more K+ efflux. Parasympathetic or vagal stimulation will hyperpolarize the SA node. If it is hyperpolarized, it is less excitable and the duration of the membrane pre-potential is longer or delayed generation of action potential. In parasympathetic or cholinergic stimulation, SA node is inhibited, heart rate decreases. The opposite happens with sympathetic stimulation, 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, making it more excitable and the heart rate increases. 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 - -90, straight line, it is stable Phase 0 depolarization, straight line. Occurs rapidly due to opening of fast voltage-gated Na channels = Na influx then reaches the threshold voltage of -60 mv resulting to depolarization. When the membrane potential reaches -20 mv, it will open up slow, long lasting voltage gated Ca channels = Ca influx. (The main factor responsible for depolarization is Na influx) Peak of the spike Na channels closes, K channels open. 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. no electrical activity. At the end of the plateau, 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 - -90 RMP is re-established. The increase membrane permeability to potassium is responsible for the -90 mv RMP. No hyperpolarization Although the K+ channels can remain open for a long time, because of the plateau, 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, fast-paced depolarization Differences: repolarization, no hyperpolarization, duration

PHOTO: Action potential of the SA node

PHOTO: Action potential of the atrium

Shannen Kaye B. Apolinario, RMT

Similarities and differences between the ventricle and atrium: Similarities: same, RMP, depolarization, phase 1 Differences: o phase 2 plateau. In the atrium, the membrane is more permeable to K+ than to Ca++. 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. 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, no fatigue, no tetanic contractions. One cannot elicit successive action potentials or contractions without tetanic or sustained contractions in the cardiac muscle = allow more time for ventricular filling. The musculature of the ventricle is thick so when it contracts, it compresses the coronary arteries. The coronary arteries supply blood and oxygen to the cardiac muscle thus when it is compressed, there is poor perfusion of cardiac muscle and less oxygen supply, this happens if there is tetanic contractions but in the cardiac muscle, there are no tetanic contractions. There is longer period of relaxation, when the ventricles are relaxed, there will be better perfusion of the cardiac muscle. Duration Action potential ARP RRP Heart rate of 75 beats per min 0.25 sec 0.20 sec 0.05 sec Heart rate 200/min 0.55 sec 0.13 sec 0.02 sec Skeletal muscle 0.005 sec 0.004 sec 0.001 sec

In Absolute or Effective Refractory Period (ARP), no amount of stimulus intensity will be able to re-excite the membrane of that cell. It covers the whole of depolarization until 1/3 of the repolarization phase. At phase 0, 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. In phases 1 and 2, 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. It is far from the CFL. In Relative Refractory Period (RRP), its level is near the critical firing level and resting level, 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.

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, if there is stimulus later in the RRP, that will open up more and more voltage gated Na channels so that its depolarization increases its amplitude, same thing happens in the SA node. 2nd Property: Rhythmicity It is said that the SA node generates the action potentials at regualr intervals. Even if the heart rate increases, if the impulses are still generated at regular intervals, that is still called the sinus rhythm.

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.

Photo: Normal ECG

Shannen Kaye B. Apolinario, RMT

P wave represents atrial depolarization QRS complex represents ventricular depolarization When seeing a normal sinus rhythm, take note of the interval between successive P waves regular interval, take note of the interval between successive QRS complex regular interval.

With regards to the right and left atrium, transmission of impulses can occur locally through gap junctions. When the impulse reaches the AV node, 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. Most of the delay will take place between the AN and N zones of the AV node. 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. The smaller fiber diameter and fewer gap junction causes increased resistance to impulse conduction - the AV nodal delay. 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. From the AV node, 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). Transmission of impulse in heart: basal. Conduction Speed in Cardiac Tissue SA node Atrial muscle AV node Bundle of His Purkinje fibers Ventricular muscle Conduction rate (m/sec) 0.05 1 0.05 1 4 1 antero-basal apex postero-basal

Photo: Sinus tachycardia

The heart rate may increase with sympathetic stimulation, during moderate to heavy exercise, and increase temperature during fever. In these three conditions, the heart rate will increase but if the impulses are generated at regular intervals, that is still sinus rhythm. But since the rate will increase, it is now called sinus tachycardia.

The part of the heart that will depolarize last is the postero-

Photo: Sinus bradycardia

On the other hand, in cold temperatures or if there is vagal over stimulation that inhibits the SA node, the rate of firing will decrease but if the impulses are generated at regular intervals, that is still sinus rhythm but this time, it is now called sinus bradycardia. If there is no rhythm or if it is irregular, it is now called arrhythmia. 3rd Property: Conductivity

Conduction speed is lowest in the AV node (not in the SA node because it is generation). Fastest is in the Purkinje fibers because of the large fiber diameter. In the atria and ventricles, conduction of impulses may occur locally through gap junctions. Reentry

Photo: Transmission of the cardiac impulse through the heart, showing the time of appearance (in fractions of a second after initial appearance at the sinoatrial node) in different parts of the heart.

All impulses from a normal functioning heart will come from the SA node. From the SA node, 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, middle internodal tract of Wenckeback and posterior internodal tract of Thorel. 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. 7 Shannen Kaye B. Apolinario, RMT

Photo: The role of unidirectional block in re-entry. In A, an excitation wave traveling down a single bundle (S) of fibers of continues down the left (L) and right (R) branches. The depolarization wave enters the connecting branch (C) from both ends and is extinguished at the zone of collision. In B, the wave is blocked in the L and R branches. In C, a bidirectional block exists in branch R. in D, a unidirectional block exists in branch R. the antegrade impulse is blocked, but the retrograde impulse is conducted through and re-enters bundle S.

A Normal direction. Coming from the SA node to the AV node to the bundle of His. From the bundle of His, the impulse will be transmitted to the left and right bundle branches. 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. 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. C Only one bundle branch is blocked (right bundle branch). 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. 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; this is called reentry or circus movement. D Since the right bundle branch is blocked, the transmission of impulse is blocked while that coming from the left will re-enter the area where the impulse came from, it goes round and round thats why it is called circus movement. 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. Since the distance is longer, when it reaches the area that is blocked, it becomes out of refractory/out of refractoriness so it can go back. Because of this phenomenon, this is the path that is responsible for atrial or ventricular fibrillation/flatter. In the synchronised contraction, the whole atria or the whole ventricle, there is an area that will contract and there is an area that will relax. 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, 2nd degree and 3rd degree heart block, all of these are abnormal conditions. The normal ratio between atrial and ventricular depolarization is 1:1, so that during atrial and ventricular contraction, if the atria will contract three times, the ventricles will also contracts three times but atrial contraction happens first than ventricular contraction causing an AV nodal delay.

1st degree heart block Incomplete heart block. All impulses from the SA node can still be transmitted to the ventricles. Based on the spacings in the photo, there is atrioventricular depolarization happening. The ratio of ventricular depolarization is still 1:1. So that when it contracts three contractions in the atria, there will also be three contractions in the ventricles. The difference from the normal is that it has a longer duration of the AV nodal delay. 2nd degree heart block Not all impulses from the SA node will reach the ventricles. What happens is P-P-QRS, P-P-QRS. This time, the ratio of the atrial to ventricular depolarization is 2:1 or 3:1. Not all the impulses reach the ventricles but since there are impulses that can reach the ventricles, this is still an incomplete heart block. 3rd degree heart block Complete heart block. No impulses from the SA node will be able to reach the ventricles. What happens is P-P-P-P. The atria will be contracting normally at a rate that is dictated by the SA node; that is 75 beats per minute. Initially, 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. The two are latent pacemakers and they are also automatic cells. For 20 seconds, there will be no impulse coming from the SA node, the latent pacemaker in the ventricle specifically the Purkinje fibers will be activated, it will escape from the overdrive suppression and this is called the ventricular escape. When activated, the Purkinje fibers will generate its own impulse causing the ventricles to contract at a rate that is dictated by the Purkinje fibers. If the contraction in the atria is 75 beats per minute, in the ventricle, it is 30-40 beats per minute. The firing of Purkinje fibers is slower than the SA node. 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. For example, there is atrial contraction that is initiated by the impulse from the SA node, other parts of the atria will be activated, and there will be an ectopic fossi impulse coming from other sources. So when it contracts, if there is another impulse, there will be another contraction and this is premature contraction or extrasystole.

PHOTO: Frequency summation and tetanization

In wave summation in the skeletal muscles, if three maximal stimuli is applied successively, the magnitude of the 2nd contraction is higher than the first because in the muscle, calcium ions have not yet returned to the sarcoplasmic reticulum and when another stimuli is applied, there will be more releasing of calcium ions that will increase the force of contraction. In cardiac muscle, the magnitude of the 2nd contraction is lower than the first. Take note that extrasystole can only be elicited during the mid or late diastole. It is not able to elicit an extrasystole during systole or early diastole because of the long duration of the Absolute Refractory Period. 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).

PHOTO: AV blocks. A, First-degree block; the PR interval is 0.28 second (normal: <0.20 sec). B, Second-degree block (2:1). C, Third-degree block; note the dissociation between the P waves and the QRS complexes

Shannen Kaye B. Apolinario, RMT

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. The longer the relaxation phase, the more blood will be filled in the ventricles, the greater the stretch of the cardiac muscle will be and the greater the force of contraction will be. 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. 4th Property: Contractility Important characteristic of a cardiac muscle: Involuntary. Activity of the heart is not controlled by the cerebral cortex, it is controlled by the autonomic nervous system although there are automatic cells present in the heart. Smaller. Compared to skeletal muscle cell, the cardiac muscle cell is smaller Either binucleated or mononucleated Striated. Just like the skeletal muscle cell, the cardiac muscle is striated. Striated means that the muscle fibers are distinctly separated from one another. What separates the individual muscle fibers is the Z line that is why the area between two Z lines will form a sarcomere. 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.

Nebulin forms the scaffold of the thin filament 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. Fair amount of elastic tissue that will enable the chambers of the heart to dilate to accommodate a greater volume of blood. Connective tissue. Presence of connective tissue that will prevent over distension or overstretching of a cardiac muscle when the cardiac size increases. More mitochondria and active capillaries. Compared to the skeletal muscle, 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. Sarcoplasmic reticulum. The sarcoplasmic reticulum in the cardiac muscle is less well developed. Meaning to say, it cant 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). 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.

PHOTO: Syncytial, interconnecting nature of cardiac muscle fibers.

Presence of the intercalated disk. The intercalated disk is present on the Z line. Its function is to separate one muscle fiber from another but at the same time, to connect one muscle fiber to another by means of gap junctions. 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, 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. The cardiac muscle cell anatomically is striated but functionally or physiologically, it is a syncytium. 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. 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. Contractile proteins present: Thick filament - myosin Thin filament actin, troponin, tropomyosin Meromyosin, C protein forms the scaffold or suport of the thick filament 9 Shannen Kaye B. Apolinario, RMT

PHOTO: Cardiac muscle (panel A) has high resistance to stretch when compared with skeletal muscle (panel B). When either cardiac or skeletal muscle is stretched, there is an increase in resting tension (RT). If the muscle is then stimulated to contract maximally, it generates more tension (termed total tension TT). The difference between total tension and resting tension at any given length is the force produced by contraction (e.g. active tension AT). The bell-shaped dependence of active tension on muscle length is consistent with the sliding filament theory of cardiac and skeletal muscle. It is, however, difficult to stretch cardiac muscle beyond its optimal sarcomere length, as evidenced by the rapid rise in resting tension in the middle of the bell-shaped AT curve.

Above is a graph that shows the importance of the presence of elastic tissue in the cardiac muscle. The blue line represents the resting tension tension that develops in the muscle before contraction. The red line represents active tension tension that develops in the muscle during contraction. Because of the many elastic tissue in the cardiac muscle, even in the resting state or resting length, passive tension increases in the muscle and it can dilate so that when the cardiac muscle fiber contracts, the difference between active and passive tension is smaller compared to skeletal muscle. The importance of that is the different chambers of the heart can accommodate a large volume of blood with little increase in pressure. Excitation-Contraction Coupling

potassium ions pumped into the cell so that it will create a concentration gradient for sodium increased concentration outside, low concentration on the inside. That will now activate the sodium-calcium exchange pump that will pump three Na+ in, 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. In patients suffering from heart failure, the main problem is poor force of contraction of the ventricle. This poor force of contraction has to be made strong by giving cardiac glycosides (e.g. digitalis). The main mechanism of action of cardiac glycosides is to inhibit the sodiumpotassium pump. If this pump is inhibited, Na+ will not be extruded so that will not create a concentration gradient for Na+. If there is no concentration gradient for Na+, 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. Arrangement of Muscle Fibers When the heart contracts, it rotates slightly to the right and that will expose the cardiac apex. The heart can rotate when it contracts because of the arrangement of muscle fibers. The arrangement of muscle fibers is synospiral and bulbospiral. 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 + 1 receptor

PHOTO: Excitation-contraction coupling in the heart requires Ca++ influx through L-type Ca++ channels in the sarcolemma and T tubules.

Present on the membrane or sarcolemma is a calcium pump, calcium-sodium exchange pump, sodium-potassium exchange pump and the last two are antiporters. Invagination of the sarcolemma will form the T-tubules. Present on the membrane of the T-tubules are voltage-gated calcium channels. Inside the cell, there are myofilament and sarcoplasmic reticulum (SR). On the membrane of the sarcoplasmic reticulum is another calcium pump. Also on the membrane of SR are ryanodine receptors and these receptors are calcium-gated calcium channels. What happens is when a membrane is depolarized, 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. 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. 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. The trigger is also Ca++ from the ECF that will bind with ryanodine receptors hence it is called calcium-gated calcium channels. It needs Ca++ from ECF to trigger movement of Ca++ from SR into the cytoplasm. That is why it has two sources of Ca++ compared to skeletal muscle the SR and ECF. If there are already many Ca++, the force of contraction is stronger. With repolarization, it is expected that the muscle will relax but for the muscle relax; 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. 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. But the most important means by which calcium is extruded from the cardiac muscle cell is through the activity of the sodium-calcium antiporter. Initially, with repolarization, the sodium-potassium pump is activated that will pump three sodium ions out in exchange for two 10 Shannen Kaye B. Apolinario, RMT

First, the sympathetic nerves that innervate the heart originate from T3, T4, and T5 segments (T = thoracic). Pre-ganglionic fibers from T3, T4 and T5 will synapse with the sympathetic ganglia and this is called the sympathetic chain. Post-ganglionic fibers from the sympathetic chain will bind with 1 receptors in the heart and the neurotransmitter agent (NTA) released by these sympathetic nerves is norepinephrine (NE). 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. Sympathetic nerves innervate ALL structures in the heart either automatic and non-automatic so that will include the sinoatrial (SA) node, atrioventricular (AV) node, ventricular conduction system or the Purkinje system as well as the atrial and ventricular muscle. Parasympathetic: CN 10 Acetylcholine + M2 SAN AVN Atrial muscle

On the other hand, parasympathetic innervation to the heart is carried by the vagus nerve which originates from the medulla. So the vagus nerve will bind with muscarinic 2 receptors in the heart and the NTA released is acetylcholine (Ache). 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. The structures in the heart that receive parasympathetic or vagal innervation are the SA node, AV node, only the proximal part of the bundle of His, atrial muscle, and there is very little, if any, vagal innervation to the ventricles. 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

In relation to this, lets look at how the autonomics regulate cardiac activity: First, regulation of heart rate is called chonotropic regulation. 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, increasing the heart rate. On the other hand, parasympathetic or vagal stimulation will inhibit the SA node, decreasing the heart rate. 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. Sympathetic stimulation will increase the velocity of conduction of impulses in the heart so it will decrease the duration of the AV nodal delay. In contrast, parasympathetic stimulation decreases the velocity of conduction of impulses in the heart prolonging the duration of the AV nodal delay. *** In parasympathetic or VAGAL stimulation, buma-VAGAL ang heart rate and velocity of conduction. 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++. Sympathetic stimulation increases the force of contraction of both the atria and ventricles. As for parasympathetic stimulation, it decreases the force of atrial contraction and it has no direct effect on the force of ventricular contraction. It has no direct effect but it has an indirect effect, that is, 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, the more the ventricular wall is stretched, and the greater will be the force of ventricular contraction. Cardiac Cycle Cardiac cycle is the sequence of events - 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. Electrical events depolarization, 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. All the electrical events taking place in the heart can be recorded by the electrocardiogram (ECG). To get an ECG tracing, electrodes are placed on the four extremities of the subject as well as on different locations on the chest wall. 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. By placing electrodes particularly on the four extremities, bipolar limb leads are formed or standard limb leads. There are three bipolar limb leads Lead I, II and III. These leads will represent electrical potential difference between two electrodes placed on two different extremities. In order to have an electrical potential difference between two electrodes, one electrode is arbitrarily designated as the negative electrode and the other one is the positive electrode.

Lead I represent electrical potential difference between electrodes that are placed on the right arm and on the left arm. In lead I, the electrode that is on the right arm is the negative electrode that of the left arm is the positive electrode. Lead II represents electrical potential difference between electrodes that are placed on the right arm and on the left leg. The electrode of the right arm is designated as the negative electrode that of the left leg as the positive electrode. Lead III represents electrical potential difference between electrodes that are placed on the left arm and on the left leg. The electrode of the left arm is designated as the negative electrode that of the left leg as the positive electrode.

PHOTO: Einthoven triangle illustrating the electrocardiographic connections for standard limb leads I, II, and III.

The electrode that is placed on the right arm is always negative and on the left leg, it is always positive. In one lead, the electrode is positive when it is located nearer on the apex of the heart. Lead II will approximate the direction of impulse transmission in the heart. So that when asked to measure the duration of the different ECG waves, the amplitude of the different ECG waves, it is preferable to use lead II because it approximates the direction of impulse transmission in the heart right arm is negative, left leg is positive (from base to apex).

Right arm (negative)

Left leg (positive)

Lead II

11

Shannen Kaye B. Apolinario, RMT

repolarization, 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. 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. When the impulse reaches the AV node, there will an AV nodal delay ad that is represented by the straight line called a P-Q or P-R segment. The P-R segment starts at the end of P up to the beginning of the QRS complex. It is a straight or isoelectric line because of the delay on the impulse transmission at the AV node. From the beginning of P to the beginning of the QRS complex is the P-R interval. The P-R interval will cover the P wave representing atrial depolarization and the P-R segment that represents AV nodal delay.

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.

Above is an example of an ECG tracing that shows electrical events in the heart in one cardiac cycle. The P wave represents atrial depolarization, QRS wave or complex represents ventricular depolarization, and T wave represents ventricular repolarization. ECG Rules: Depolarization (+) electrode = upward

QRS complex will represent ventricular depolarization. It is a complex made up of three waves. In the QRS complex, 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. 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. R wave is a very high positive deflection that represents depolarization of the cardiac apex that is definitely towards a positive electrode. Then there is a second downward deflection which is the S wave. 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, 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. T wave is only a part of ventricular repolarization because ventricular repolarization starts at the end of QRS complex. So from the end of S wave to the beginning of T wave, there is an isoelectric line or the S-T segment. Recall the action potential generated in the ventricle, the phase of repolarization that represents the S-T segment is the plateau or phase II. There is a straight line because of the equal conductance of Ca+ and K+; there is no change in membrane potential. 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. In the ventricles, the repolarization does not follow the direction of depolarization, unlike in the atria. Repolarization will occur in the opposite direction: from posterobasal apex anterobasal. It is moving away from a positive electrode because from the apex, it will go up hence 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. So when it is said ventricular repolarization, it is actually the S-T interval, from the end of S to the end of T, not just the T wave. Mechanical events Following depolarization, the atrial and ventricular muscles will contract and it is called the systole. 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, it is recorded as an upward or positive deflection. On the other hand, if depolarization will move away from a positive electrode, it is recorded as a downward or negative deflection. In repolarization, if the electrode moves toward a positive electrode, it is recorded as negative or downward deflection and if repolarization will move away from a positive electrode, it is recorded as an upward or positive deflection. Remember that in lead II, the positive electrode is on the left leg.

P wave

P wave - atrial depolarization, it is a positive deflection. 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. That is why the P wave is recorded as an upward deflection. There is no ECG wave that represents atrial repolarization because atrial repolarization occurs simultaneously with ventricular depolarization. If ever there is an ECG wave that will represent atrial 12 Shannen Kaye B. Apolinario, RMT

cardiac cycle, blood is ejected from the different chambers of the heart. Following repolarization, the muscles will relax and it is called diastole. During diastolic phase, there will be filling of blood in the different chambers of the heart. The average duration of one cardiac cycle is 0.8 second. The duration of the systolic phase is 0.27 second and that of the diastolic phase is longer which 0.53 of a second and this happens at the heart rate of 75 beats per minute. When the heart rate increases, the duration of the cardiac cycle will decrease so the duration of the systole and diastolic phases is also decreased. 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. Correlation of the Electrical and Mechanical Events in the Heart in One Cardiac Cycle SAN atr. depo (P wave) AVN VCS delay (P-R segment) vent. depo (QRS) atr. repo VP > AP atr. systole inc. VF vent. systole atr. diastole inc. VP dec. AP 20% VF inc. AP (a wave)

An impulse will be generated from the SA node transmitted to the AV node. Transmission of the impulse from the SA node to the AV node is facilitated by the three internodal tracts: Bachman, Wenckeback and Thorel. In the process, the atria will undergo depolarization recorded in the ECG as the P wave. The response of the atrial muscle to depolarization is to contract so there will be atrial systole. When the atria contracts, although it is a weak pump, there is still blood ejected to the ventricles and that will account for only 20% of ventricular filling. When the atria are contracting, 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. A wave is not an ECG tracing, it is only a label to the increase atrial pressure during atrial systole. When the impulse reaches the AV node, there will be a delay called the AV nodal delay, in the ECG that is recorded as the P-R segment. The importance of the AV nodal delay is that it will provide more time for ventricular filling. From the AV node, 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. The response of the ventricular muscle to depolarization is to contract so following ventricular depolarization will be ventricular systole. When the ventricles contract, the ventricular pressure increases. Simultaneous with ventricular depolarization is atrial repolarization and no ECG wave represents atrial repolarization. The response of the atrial muscle to repolarization is to relax so atrial diastole happens. Since the atria is relaxed, there will be a decrease in the atrial pressure. When the ventricular pressure exceeds atrial pressure, there will be a pressure gradient and that will now close the AV valves therefore the first heart sound will be heard. There will be a condition wherein the SL are still closed and the AV valves are now closed, there is no change in ventricular volume because all the cardiac valves are closed but since the ventricles are contracting, there is increase in ventricular pressure and this is called isovolumic or isovolumetric contraction phase of the cardiac cycle. When the ventricles are contracting, 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. But remember that the AV valves does not over-bulge into the atria when the ventricular pressure is increased because when the ventricles contract, 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. When ventricular pressure exceeds 80 mmHg, 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. But when it is ejecting more and more blood, the volume of the blood in the ventricles as well as ventricular pressure will start to decrease. 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, 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, there will be atrial filling. The ventricles will undergo repolarization so this is the S-T interval in the ECG. The response of the ventricular muscle to repolarization is to relax so there will be ventricular diastole therefore ventricular pressure will start to decrease. Pressure in the aorta or in the arterial system is always high so that when arterial or aortic pressure now exceeds ventricular pressure, this will close the semilunar valves and that will produce the second heart sound. But there is a short interval of time between ventricular diastole and closure of SL valves which is called protodiastole. There will be a condition again wherein the SL valves are now closed, the AV valves are still closed so there is no change in ventricular volume but since the ventricles are in a relaxed state, ventricular pressure decreases and this is called isovolumic relaxation. At the same

close AV valves (1st heart sound)

isovolemic contractions: slight inc. AP (C wave) VP > 80 mmHg open SL valves rapid ejection reduced ejection; atrial filling vent. repo vent. diastole dec. VP (S-T interval) AP > VP protodiastole close SL valves (2nd heart sound) isovolemic relaxation; inc. atr. filling; inc. AP (V wave) AP > VP open AV valves rapid inflow diastasis reduced inflow of blood to the ventricles atr. atrial AV - antrioventricular AVN atrioventricular node dec. - decrease depo depolarization inc. - increase repo repolarization SAN sinoatrial node SL - semilunar vent. ventricular/ventricle VF- ventricular filling VP ventricular pressure

At the beginning of one cardiac cycle, before an impulse is generated from the sinoatrial (SA) node, the atrium and ventricles are all relaxed atrial systole and ventricular diastole. 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. In fact, 80% of ventricular filling (VF) takes place when all four chambers of the heart are in a relaxed state. It is not needed for the atria to contract to have ventricular filling because its contraction is weak primer pump, so whenever the AV valves are open, there is 80% of ventricular filling. 13 Shannen Kaye B. Apolinario, RMT

time as isovolumic relaxation, the atrial filling increases which will again increase atrial pressure and is called the V wave. When atrial pressure exceeds ventricular pressure, 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. When there is more blood filled in the ventricle, 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. From that, there will be another impulse from the SA node beginning another cycle. All of these events take place in the heart for 0.8 second. Cardiac Cycle

Ventricular pressure is initially low. It will increase slightly during atrial systole because of the additional volume of blood that will be ejected by the atria to the ventricles. Ventricular pressure will actually increase during isovolumic contraction and still high during the period of ejection of blood. But as the volume of blood in the ventricles decreases, ventricular pressure will also decrease. It will continue to decrease during the period of isovolumic relaxation. It will remain low during the periods of rapid inflow of blood to the ventricles and diastasis. Again, slight increase with atrial systole because of the additional volume of blood ejected from the atria to the ventricles. Closing of the AV valves will mark the onset of isovolumic contraction. Remember that in isovolumic contraction, all the cardiac valves are closed so there will be no change in the volume of ventricles. So that means at that point, the first heart sound will be heard. Opening of the AV valves mark the end of isovolumic relaxation so there will be period of ventricular filling. What will happen at the end of isovolumic contraction? There will be opening of the SL valves. While at the beginning of isovolumic relaxation, the SL valves close so the second heart sound will be heard. 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. 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. 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. So if the volume of blood in the aorta is greater, there will be greater force exerted by that volume of blood on the aortic wall. During the period of reduced ejection, the aortic pressure decreases because there will be peripheral run-off blood, meaning to say, blood that is contained in the aorta will now be distributed to the arteries, to the arterioles, 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. When the aortic wall recoils, 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. All throughout the period of ventricular diastole, the aortic pressure is stable and is slightly low but it is still higher compared to the 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.

*** Ventricular pressure curve green line 1st heart sound 14 AV valves open

Shannen Kaye B. Apolinario, RMT

Ventricular Volume Curve

The 3rd heart sound heard in abnormal conditions is due to ventricular filling. There is an increase in ventricular filling coinciding with the appearance of the 3rd heart sound.

At the start, there is additional increase in volume with atrial systole additional 20% of ventricular filling. During isovolumic contraction, all cardiac valves are closed so there is no change in the ventricular volume. During period of rapid ejection, blood is ejected from the ventricles so the ventricular volume will decrease. In the period of isovolumic relaxation, all cardiac valves are closed so there is no change in ventricular volume. During the period of rapid inflow, there is a very high increase in ventricular volume. It is somewhat stabilized in diastasis and a slight increase again during atrial systole. Atrial Pressure or Central Venous Pressure (CVP) Curve

c c

PHOTO: Left atrial, aortic, and left ventricular pressure pulses correlated in time with aortic flow, ventricular volume, heart sounds, venous pulse, and the electrocardiogram for a complete cardiac cycle.

Ventricular Volume Pressure Curve (Ejection Loop) A wave is increase in atrial pressure during atrial systole. 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. The V wave is increase atrial pressure during isovolumic relaxation where it is simultaneous with the increase in atrial filling. Heart Sounds The 1st heart sound is due to closure of the AV valves. Closure of the AV valves will mark the onset of the period of isovolumic contraction so when seen at the ventricular volume curve, it is a straight line no change in ventricular volume. 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. Again, there is no change in the ventricular volume. 15 Shannen Kaye B. Apolinario, RMT

PHOTO: Relationship between left ventricular volume and intraventricular pressure during diastole and systole. Also shown by the heavy red lines is the volume -pressure diagram, demonstrating changes in intraventricular volume and pressure during the normal cardiac cycle. EW, net external work.

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, the unit is mmHg. The horizontal axis represents changes in ventricular volume and the unit is either cc or mL. In relation to changes in ventricular volume and pressure, the cardiac cycle is divided into four phases. The letters represent each point. Point A - ventricular volume is 50 mL. This 50 mL is actually the volume of blood remaining in the ventricles after contraction. At 50 mL, the pressure is low a little above 0 mmHg. At point A, the atrioventricular valves open. Phase I from 50 mL, the volume of blood in the ventricles increased to 120 or 130 mL but there is little increase in pressure. Phase I is ventricular filling. Point B - the volume of blood is 130 mL. There is closing of the AV valves so the first heart sound is heard. Phase II the volume of blood is 130 mL and the pressure continues to increase. At phase II, there is period of isovolumic contraction. Point C opening of SL valves. When the SL valves open, the ventricular pressure still increases but the volume is already decreasing. From C prime, it is the period of rapid ejection. Phase III in the latter part of Phase III the volume decreases and the pressure decreases, this is now the reduced ejection. Point D closing of the SL valves so the second heart sound is heard. Phase IV the volume of blood is still 50 mL but the pressure is decreasing and decreasing. This is isovolumic relaxation. I can do EVERYTHING through Him who gives me strength -Philippians 4:13 GOD BLESS YOU!

16

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Cardiodynamics (Gloria Marie M. Valerio, 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, 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, although the workload of the left ventricle is greater than that of the right ventricle, although the left ventricular wall or musculature is thicker than that of the right ventricle, the output of the two ventricles are the same. Heart Rate (HR) the number of contractions/heart beats/cardiac cycles per minute Normal Value (normal resting adult): 75 beats per min. * In a normally functioning heart, the heart rate and rhythm are determined by the activity of the SA node. 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. End Diastolic Volume (EDV) is the amount/quantity/volume of blood in the ventricles at the end of diastole, before systole = PRELOAD Normal Value: 110-130 mL * Whatever amount of blood that will be present in the ventricles after the ventricular filling time, before contraction of the ventricle; that is the end diastolic volume. 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. 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. No matter how strong the force of ventricular contraction is, there will always be a certain amount of blood that will remain in the ventricles.

Correlation of SV, EDV, ESV with the Ejection Loop From point D to point A, the volume of blood increases in the ventricles with little increase in pressure, this is the ventricular filing time. At point A, the atrioventricular (AV) valves will close so that whatever amount of blood will be present in the ventricles before closure of the AV valves, that is now the end diastolic volume (EDV) which is a little less than 150 mL, average of 130 mL. From point A to point B, the ventricles will now start to contract, but since all the valves are closed, there will be no change in ventricular volume. From point B to C, 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. At point C, the semilunar (SL) valves will close, the ventricles will start to relax and the volume of blood that is now in the ventricles is the end systolic volume (ESV). Stroke volume is equal to EDV minus ESV or ESV + SV will be the EDV. CO = SV x HR EDV ESV Whatever factor that will affect EDV and ESV will also affect the SV. Whatever factor that will affect the SV and HR will affect the CO. As for the SV, this is determined mainly by the force of myocardial contraction. So if the force of myocardial contraction increases, the SV will increase. On the other hand, if the force of myocardial contraction decreases, the SV will also decrease. We can therefore say that the HR, SV as a reflection of the force of myocardial contraction are factors intrinsic to the heart that will affect the cardiac output. But aside from factors intrinsic to the heart, there are also factors outside the heart called peripheral factors that may also affect the cardiac output. What are the factors outside the heart that may affect the cardiac output? 1. Total blood volume 2. Status of the venous sytem that will deter blood back to the heart 3. 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. The heart and the vascular system are actually inter-dependent and that is because of the close nature of the cardiovascular system. 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, before contraction.

PHOTO: Preload

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Take note of where the black arrows are directed. These black arrows represent the EDV. It is directed towards the ventricular wall so the greater the volume or EDV, the greater the force that will be exerted on the ventricular wall. If the force exerted on the ventricular wall is greater, that will now stretch the ventricular wall and if the ventricular wall is stretched, that will now increase the force of myocardial contraction. So in other words, the greater the EDV, the more the ventricular wall is stretched, the greater will be the force of contraction. And if the force of contraction is increases, stroke volume increases, cardiac output increases. So EDV is directly related to cardiac output. Factors Affecting EDV 1. Effective filling time

Both of the equations are true but there is a range of heart rate. The horizontal axis on the graph represents heart rate while the vertical axis represents cardiac output. Based on the graph, when the heart rate increases from 060 beats per minute, there is a corresponding increase in cardiac output. They are directly related because when the heart rate increases from 0-60, 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. In the first phase, sympathetic stimulation increases the heart rate. Sympathetic stimulation increases not only the heart rate but also the force of contraction. When the heart rate increases, the stroke volume increases therefore the cardiac output increases. When the heart rate increases from 60-180 beats per minute, the duration of the filling time is quite affected but still, the ventricles can still be filled with blood because from 60-180 beats per minute, the increase in heart rate is equal to the decrease in stroke volume so that the cardiac output is maintained at a constant level. When the heart rate increases from 180 beats per minute and above, the duration of the filling time is now severely compromised. And sympathetic stimulation can no longer compensate on the very short duration of filling time. So the increase in heart rate is now less than the decrease in stroke volume so the cardiac output will now decrease. There is a range wherein the cardiac output will start to decrease with an increase in heart rate. If you will recall, if the heart rate is 75 beats per minute, the duration of one cardiac cycle is 0.8 sec, the duration of the systolic phase is 0.27 sec, and much longer is the duration of the diastolic phase which is 0.53 sec. 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, 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 0.80 sec Systole 0.27 sec Diastole 0.53 sec Heart Rate 200 beats/min 0.30 sec 0.16 sec 0.14 sec

Filling time refers to the duration of the diastolic or relaxation phase because that is when the ventricles are filled with blood. FT EDV SV CO

If the duration of filling time increases, there will be enough time for the ventricles to accommodate a larger volume of blood so the EDV increases. Again, if the EDV is greater, the greater the ventricular wall is stretched, the greater the force of contraction so the SV as well as the CO increases. All are directly directed. HR FT EDV SV CO

One factor that will influence the duration of the filling time is heart rate. When the heart rate increases, 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. HR FT EDV SV CO

The reverse is also true that when the HR decreases, the duration of the filling time will increase, more EDV, SV and CO. Increased HR decreases the CO and decreased HR increases the CO but going back to the formula: CO = SV x HR, heart rate is directly related to CO, meaning to say that an increase in HR will increase the CO. Which among the formula is true? In the formula, it is directly related and of course that is true. If the HR increases, there will be an increase in the frequency of depolarization on the sarcolemma of the cardiac muscle cell. So the more the cardiac muscle is depolarized, the more Ca++ enters the cell and if more Ca++ enters the cell, the greater the force of contraction, the more the stroke volume increases, increased cardiac output. That is how an increase in HR will increase the CO. What about the other equation?

When the heart rate increases to 200 beats per minute, the duration of cardiac cycle will decrease from 0.8 to only 0.3 sec but if you will compare the decrease in the duration of systole and diastole, diastole is more affected (bigger decrease in duration of diastole) from 0.53 to 0.14 sec which means that the filling time is really compromised and the EDV is severely decreased. 2. Effective filling pressure EFP = CVP ITP EFP - effective filling pressure CVP central venous pressure ITP intra-thoracic pressure Aside from the duration of the filling time, another factor that may influence the diastolic volume is the effective filling pressure or transmural pressure - pressure difference between the inside and outside of the heart. Pressure inside the heart is the central venous pressure while outside is the intra-thoracic pressure. The greater the difference between the pressure inside and outside of the heart, the greater the effective filling pressure. And when the effective filling pressure is greater, that will now distend the ventricles, allowing the ventricles to accommodate a larger EDP. 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.

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3.

Myocardial compliance

All elastic structures have the property of compliance and that is the measure of distensibility or stretchability of an elastic structure. C=V P Compliance is equal to change in volume over change in pressure. For a structure to have an increase in compliance, the change in volume should be higher or greater compared to the change in pressure. And this is true for the ventricles, 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. 4. 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. Because of the closed nature of the cardiovascular system, whatever volume of blood that will return to heart per minute, will be effectively ejected or pumped by the heart per minute so that means venous return is equal to cardiac output. The average venous return is also 5 L or 5,000 mL per minute. 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. So if the force of myocardial contraction increases, SV will increase, ESV will decrease. If the force of myocardial contraction decreases, SV will decrease, ESV will increase. In other words, force of myocardial contraction is inversely related to the end systolic volume (ESV).

Within physiologic limits, 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. 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. the greater the EDV, the greater will be the force exerted on ventricular wall, the more the ventricular wall will be stretched and that will now increase the force of contraction and this is called heterometric autoregulation. Autoregulation means that the heart itself can regulate its own force of contraction. Metric is the length. Hetero - changes. So the change in the length of cardiac muscle will enable the heart to regulate its own force of contraction. 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. There is a limit because when the cardiac muscle is overstretched or distended, 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, it becomes weak. 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. 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. 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. But during atrial systole, there is an additional amount of blood that will be ejected to the ventricles so the EDV increases. If the force of contraction in the atria is greater, there will be more than the 20% that will be added in the ventricular filing, the EDV will be more increased. Increased total blood volume. Total blood volume is actually one factor that will affect venous return. So if the total blood volume increases, venous return will increase, EDV will also increase so that will stretch the ventricular wall. Increased venous tone. One property of smooth muscle cells present in the vascular wall as well as in the visceral wall is the tone. For example, the stomach and the small intestinal wall have a tone, the same is also true with blood vessels, arteries and veins - their wall has a tone. When the smooth muscle layer in the veins contract, there will be veno-constriction, the blood cannot go back to the heart. 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. If the venous wall is in a relaxed state, the blood in the veins cannot go back to the heart. So what is venous tone? Tone means state of partial contraction. One property of smooth muscle is they can remain partially contracted for a long time. If the wall of the veins is partially contracted, 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. Increased pumping of skeletal muscle. When you remain in a standing position for a long time, blood pools in the veins of the lower extremities. So again, if there is pooling of blood in the veins of the lower extremities, the venous return will decrease, EDV will decrease, 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, SV increases so the remaining part becomes smaller. Since the force of myocardial contraction will affect the ESV, 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 starlings Law . Factors Affecting ESV a. 1. Force of myocardial contraction Frank Starlings Law

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stretched. But once you move, the skeletal muscle will contract and that will compress the veins. When the veins are compressed, that will open up the venous valves. The opening of the valves is directed toward the heart. So when the veins are compressed by skeletal muscle contraction, venous valves will open and blood will return to the heart. * The three factors: increased total blood volume, increased venous tone and increased pumping of the skeletal muscle will first influence venous return. Venous return will then influence EDV, EDV is the one that will exert force on the ventricular muscle to stretch the ventricular muscle. Increased negative intrathoracic pressure. Increased negative intrathoracic pressure allows the ventricles to distend, so that will stretch the ventricular muscle.

But that is not the end of sympathetic effects. It does not allow Ca++ to always enter the cell because when it always depolarizes, more Ca++ will enter the cell. But hidni dun nagtatapos ang sympathetic effects. Hindi lang basta nagpapapasok ng ca kasi malimit magdepolarize, mas madaming ca na papasok Another action of sympathetics is when norepinephrine and epinephrine bind with 1 receptors in the heart, this will cause activation of G-proteins. 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). As a second messenger, 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). One action cAMP-PK is to phosphorylate the Ca++ channels on the sarcolemma. When it is phosphorylated, that will allow more Ca++ to enter that will increase the force of myocardial contraction. But take note that sympathetic stimulation will increase not only the force of contraction; it will also facilitate relaxation of the cardiac muscle by the action of cAMP-PK. So another action of cAMP-PK is to phosphorylate troponin I so that troponin cannot bind with Ca++. If troponin cannot bind with Ca++, the muscle will relax because troponintropomyosin complex will go back to cover the active site of actin due to absence of troponin-Ca++ complex. Another action of cAMP-PK is to phosphorylate an intracellular protein called phospholamban. The normal action of phospholamban is to inhibit the Ca++ pump on the sarcoplasmic reticulum. If the Ca++ pump is inhibited, Ca++ will not return it will remain bound to troponin C so there will still be muscle contraction. But once phosphorylated by cAMPPK, the inhibitory effect of phospholamban will decrease so the Ca++ pump will be activated and when activated, 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. So again, aside from increasing the force of myocardial contraction, sympathetic stimulation can also facilitate relaxation of the cardiac muscle. 3. Calcium

All of these are factors will affect cardiac muscle length before contraction. So if these factors will increase, cardiac muscle length will increase before contraction so that during contraction, the force of myocardial contraction will increase. 2. 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, norepinephrine, epinephrine; and parasympathetic that will release acetylcholine. Sympathetic stimulation will increase the force of contraction of both the atria and ventricles primarily because norepinephrine binds with 1 receptors will increase membrane permeability to calcium allowing more Ca++ to enter myocardial cell and that will increase the force of contraction. But aside from this, sympathetic stimulation can also increase the heart rate so the more frequent the myocardial cell is depolarized, again, the more Ca++ will enter the myocardial cell and that will increase the force of contraction. In contrast, vagal or parasympathetic stimulation by releasing acetylcholine will decrease the force of atrial contraction. It has no direct effect on the force of ventricular contraction because there is very little, if any parasympathetic or vagal innervation to the ventricles.

Another important factor that will affect the force of myocardial contraction will be the amount Ca++ available that will bind with troponin C. In contrast to the skeletal muscle, there are two sources of Ca++ for myocardial contraction: sarcoplasmic reticulum and ECF. That means that the plasma Ca++ level will have an effect on the force of myocardial contraction. 4. Adequate coronary flow

Another factor is adequacy of the coronary arteries. Remember that the coronary arteries supply blood and oxygen to the cardiac muscle itself. So when there is an obstruction (e.g. thrombus or embolus) in one of the branches of coronary arteries, there will be an area of that myocardium that will be deprived of oxygen supply so the area will be ischemic. If the ischemic area is not corrected, it will cause necrosis to the tissue developing an infarct and that infarcted area cannot contract anymore. Since there is an area in the myocardium that is not contracting, the overall force of contraction will decrease and that will predispose to ventricular or heart failure. 5.
PHOTO: Schematic diagram of the movement of calcium in excitation-contraction coupling in cardiac muscle. Influx of Ca++ from interstitial fluid during excitation triggers release of Ca++ form the sarcoplasmic reticulum (SR). The free cytosolic Ca++ activates contraction of the myofilaments (systole). Relaxation(diastole) occurs as a result of uptake of Ca++ by the SR, by extrusion of intracellular Ca++ by the 3 Na+-1 Ca++ antiporter, and to a limited degree by the Ca++-ATPase pump. R, -adrenergic receptor: cAMP-PK, cAMP-dependent protein kinase.

Heart rate

The force of myocardial contraction can also be influenced by heart rate. It is mentioned earlier that when the heart rate increases, the depolarization of cardiac muscle will be more frequent and remember that with each depolarization, it allows more Ca++ to enter and that will increase the force of contraction.

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Factors that influence or regulate heart rate: Autonomics. The most important factor. 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. On the other hand, parasympathetic or vagal stimulation will make the SA node more permeable to K+ so that will hyperpolarize the SA node making it less excitable, decreasing the heart rate. Hormones. Aside from the neurotransmitters released by the autonomic nerves, heart rate can also be affected by several hormones one of which is cortisol - corticosteroids from the adrenal cortex. The effect of cortisol is to potentiate the effect of epinephrine so that means increased corticosteroids may increase the heart rate. Other hormones are T3 and T4 thyroid hormones. Thyroid hormones directly stimulate the SA node so that one clinical manifestation of hyperthyroidism is tachycardia. Neural reflexes. 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. These reflexes that regulate arterial blood pressure can also regulate heart rate. Bainbridge reflex. This time, when venous return 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. When the right atrial wall is stretched, the SA node is stimulated and that will increase the heart rate. So this Bainbridge reflex is sensitive to an increase in blood volume that will return to the right atrium. Exercise. During exercise, heart rate increases for two reasons: increased metabolism and increased sympathetic stimulation. Excitement and anxiety. Emotions like excitement and anxiety will also increase the heart rate partly because of increased sympathetic stimulation. Temperature. Increased environmental temperature can also increase the heart rate. Not only environmental temperature but also body temperature so when there is fever, heart rate increases.

7.

Afterload

Afterload is the aortic pressure load, opposing force to left ventricular contraction. Why in the aortic artery only and not in pulmonary artery? Because remember that there is low/no pressure area in the pulmonary circulation, not much resistance to right ventricular contraction unless there is pulmonary hypertension. More of the resistance happens in the left ventricle because there is high pressure area in the arterial system. So when we say afterload, it is the pressure in the aorta.

PHOTO: Afterload

Remember the photo on preload, the arrows are directed on the ventricular wall because the EDV exerts force on the ventricular wall to increase the force of contraction. When the ventricles contract, 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, EDV will have a hard time to go out. So if the aortic pressure increases, stroke volume decreases, end systolic volume increases and this is shown on the photo below:

6.

Cardiac glycosides

Cardiac glycosides are given to patient suffering from congestive heart failure. The main purpose of giving cardiac glycosides is to increase the force of myocardial contraction. When the muscle is relaxed, the Na-K pump is activated. 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. If the Na+-Ca++ pump is activated, 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. It is needed for the Ca++ to remain inside the cell to have an increased force of contraction. 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. If the Na-Ca pump is not activated, 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.

The normal stroke volume is still represented by the red line. When the aortic pressure increases, the tendency of the ventricles is to increase its contraction because the pressure against it is stronger. Thats why the pressure in the ventricles is increasing and increasing but because the opposing force is greater, stroke volume is decreased and the end systolic volume is increased. So what is the consequence of that? There is much left so in every venous return, what will happen in the EDV? There is much left but

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even if there is less amount that goes out, some will still go back to the heart, 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. When the EDV is increased, the ventricular wall will be stretched; its contraction will be increased. But even if the contraction is increased but there is persistent increase in aortic pressure, 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. Since the SV is less, 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.

To summarize the factors that will determine the cardiac output, there are factors intrinsic to the heart and there are factors outside the heart. Factors intrinsic to the heart will include the heart rate and the force of myocardial contraction. Factors outside the heart or peripheral/coupling factors will include the preload (factors that will affect EDV) and afterload or aortic pressure load. 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. Eating (30%) eating increases blood flow to the gastrointestinal tract. Increase in blood flow increases venous return and increases cardiac output. Exercise (up to 700%) increased metabolism, sympathetic stimulation. Increased environmental temperature Pregnancy due to increased blood volume that will increase venous return. 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. Heart diseases examples are congestive heart failure, myocardial infarction, cardiac valve diseases, arrhythmias, chronic hypertension all of these factors that will decrease the force of myocardial contraction.

PHOTO: Pressure-Volume Loop. Cardiac output is the volume of blood pumped by the heart each minute. In the steady state the output from both the right and left ventricles is the same. The pressure-volume loop for the left ventricle is depicted here. 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. Increases in arterial pressure (increased afterload) decrease stroke volume and thus cardiac output (lower panel).

No change Sleep Moderate change in environmental temperature

8.

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. If the aortic valve hardens, even if the ventricular pressure is greatly increased, the SV and cardiac output will still be diminished. Blood will again accumulate in the left ventricle and eventually, the left ventricle will dilate so the force contraction will decrease. 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. In patients suspected of having congestive heart failure, one procedure that is requested is 2-D echocardiogram to determine the ejection fraction (EF). Because if the EF falls below what is normal, it means that the SV is decreased and it is decreased because the ventricular contraction is weak.

Cardiac Output

Myocardial contractility 6

Afterload

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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. It means that in the elderly where the physical activity is less, the skeletal muscles atrophy so the body surface area decreases and the cardiac output and cardiac index is decreased. Compared to the athletes who have welldeveloped muscles, 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, the heart compensates so the CO increases. Cardiac Reserve Maximum percentage that cardiac output can increase above normal (300-600%)

In certain conditions, the CO may be increased from 5L to 1315 L per minute and that is called a hypereffective heart. Hypereffective because the heart can pump blood a volume that is greater than what is normal. Hypereffective heart happens if there is sympathetic stimulation and parasympathetic inhibition, during moderate to heavy exercise or during athletic activities that will involve endurance (e.g. 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.g. congestive heart failure, rapid arrhythmia, cardiac valvular diseases).

Ask and it will be given to you; seek and you will find; knock and the door will be opened to you. For everyone who asks receives; he who seeks finds; and to him who knocks, the door will be opened. -Matthew 7:7-8 GOD BLESS YOU 7 Shannen Kaye B. Apolinario, RMT |

Circulatory or Vascular System (Gloria Marie M. Valerio, 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. Take note that the blood vessels are not rigid tubes, they are distensible. The primary function of the circulatory system is to service the needs of the tissues that is - by transporting blood, 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. As what we have learned from the previous lecture, the circulatory system is divided into two pulmonary and systemic circulation. The pulmonary circulation receives unoxygenated or venous blood from the right heart and supplies blood to the lungs. On the other hand, 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. Since the systemic circulation will supply blood to almost all organs of the body, it is also called peripheral or greater circulation. Blood Vessels

In the different organs of the body, the arteries will divide into smaller branches forming the arterioles. This time, the wall of the arterioles contains more smooth muscle fibers than elastic tissue . In fact, among all the different types of blood vessels, 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, that will decrease tremendously blood flow to the capillaries and to the tissues. On the other hand, when the smooth muscle layer of the arteriolar wall relaxes or if there is vasodilatation, that will now increase tremendously blood flow to the capillaries and to the tissues. 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, resistance to blood flow is highest in the arterioles so the arterioles are called resistance vessels. The smallest blood vessels are the capillaries. The capillary wall is thin and porous - it allows exchange of fluids and some solutes between intravascular and interstitial fluid compartments. The capillaries are known as exchange vessels. From the capillaries, blood will be collected by the venules which will then coalesce to form the bigger veins. Comparing the wall of the vein to that of an artery, 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. It means that the vascular capacity is bigger and veins are also called capacitance vessels. There are two functions of veins: one is to act as blood reservoir and another one is to return blood back to the heart. In the veins of the limbs or extremities, there are venous valves present with openings of which are directed towards the heart. So that when you move your limbs and the skeletal muscles contract that will open up the venous valves and facilitate venous return. Layers of the Blood Vessel 1. 2. 3. Tunica intima Tunica media Tunica adventitia

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).

On the right is the arterial system or distributing vessels. On the left is the venous system or collecting vessels. When the left ventricle contracts, blood is ejected to the aorta and from the aorta to the arteries. 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 . One important characteristic of the aortic as well as arterial wall is that it contains more elastic tissue than smooth muscle fibers . So that will make the aortic and arterial wall highly distensible so during ventricular systole, when blood is ejected to the aorta, the aortic wall will distend to accommodate the large volume of blood. On the other hand, during ventricular diastole, the aortic and arterial wall will recoil on the contained blood. 1 Shannen Kaye B. Apolinario, RMT|

Except for the capillaries, the wall of the different blood vessels is made up of the same structure. There are three layers of the vascular wall. The innermost layer is the tunica intima which is made up of the endothelium and basement membrane. The middle layer is the tunica media which is made up of smooth muscle fibers. The outermost layer is the tunica adventitia which is made up of connective tissue. Just like in the heart, 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.

Properties and Characteristic of the Vascular Smooth Muscle 6. 2 types of Smooth Muscle 1. 2. Multiunit Single unit 7.

structures which are called calveolae. However, this calveolae are actually analogous to the T-tubules. Few mitochondria. There are fewer mitochondria in the smooth muscle and the main source of energy for contraction is glycolysis. Sarcoplasmic Reticulum. 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, there has to be another source of calcium ions and that is the extracellular fluid (ECF). 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. Contractile Proteins. Contractile proteins are also present that will include actin, myosin and tropomyosin but there is no troponin so in order to contract, calcium will bind with another protein and that is calmodulin so you have a calcium-calmodulin complex that will initiate vascular smooth muscle contraction. Stimuli. Stimuli that will cause contraction of the vascular smooth muscle. Remember that in the skeletal muscle, the primary stimulus will be neural or nervous. 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. In vascular smooth muscle, there are different types of stimuli that can stimulate the vascular smooth muscle: a. Neural. 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. Sympathetic adrenergic nerves innervate the blood vessels in the skin and viscera while sympathetic cholinergic nerves innervate the blood vessels in the skeletal muscle. The neurotransmitter agent that is released by sympathetic nerves is norepinephrine. 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. On the other hand, when either norepinephrine or epinephrine binds with beta-2 receptors, that will cause relaxation of the vascular smooth muscle so there will be vasodilatation. Remember in relation to beta-2 receptors, epinephrine has a greater effect than norepinephrine. In sympathetic cholinergic, you have acetylcholine binding with muscarinic receptors that will also relax the vascular smooth muscle in the skeletal muscle so there will be vasodilatation. b. Hormones. Aside from neural, the vascular smooth muscle can also be stimulated by circulating hormones which could either be vasoconstrictors or vasodilators. Among the circulating vasoconstrictors are angiotensin 2 and vasopressin or antidiuretic hormone (ADH). Among the circulating vasodilators are bradykinin and histamine. Stretch. Stretch of the muscle will initiate a reflex action. For example, when the blood volume and blood pressure increased, that will now stretch the arterial wall that will initiate a reflex action that will cause vasoconstriction. Local factors. Local factors for example actively metabolizing tissue so there will be oxygen consumption and production of carbon dioxide. So that oxygen tension (pO 2) will decrease and pO2 pCO2 carbon dioxide tension (pCO 2) will increase, these two factors will also cause vasodilatation. pH = H+

8.

9.

PHOTO: Control systems of smooth muscle. Contraction (or inhibition of contraction) of smooth muscles can be initiated by (1) the intrinsic activity of pacemaker cells, (2) neutrally released transmitters, or (3) circulating or locally generated hormones or signalling molecules. The combination of a neurotransmitter, hormone, or drug with specific receptors activates contraction by increasing cell Ca++. 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. Hormone concentrations depend on diffusion distance, release, uptake, and catabolism. Consequently, 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. A. Multiunit smooth muscles resemble striated muscles in that there is no electrical coupling and neural regulation is important. B. Single-unit smooth muscles are like cardiac muscle, and electrical activity is propagated throughout the tissue. Most smooth muscles probably lie between the two ends of the single unit-multiunit spectrum.

There are two types of smooth muscles in the body: multi-unit smooth muscle and single unit smooth muscle. In the visceral wall as well as the vascular wall, the type of smooth muscle fibers present is mostly the single unit type. Characteristics of Smooth Muscle 1. 2. Smaller. Compared to the skeletal muscle cell, the smooth muscle cell is smaller Involuntary. The activity of the vascular smooth muscle is not regulated by the cerebral cortex. Resting Membrane Potential. The RMP is less negative, it is also unstable. It ranges from -50 to -60 mv. 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. So that the duration of the contraction-relaxation cycle in the vascular smooth muscle is also longer. Tonic contraction. Another important property of the vascular smooth muscle - it can remain partially contracted for a long time with little expenditure of energy and that is what we call tonic contraction. Sarcolemma. 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. Also present is a calcium pump, a sodium-potassium anti-porter, and a sodiumcalcium anti-porter. However, invaginations of the sarcolemma will not form the T-tubules; instead the invaginations will form cave-like 2 Shannen Kaye B. Apolinario, RMT|

3.

c.

4.

d.

5.

Other local factors that will cause vasodilatation will include a decrease in plasma pH so increase hydrogen, increase lactic acid concentration. Increase potassium, increase adenosine, all of these will produce vasodilatation. There are several factors that can either stimulate or inhibit the vascular smooth muscle. Contraction-Relaxation Cycle

Latch-Bridge Mechanism Repolarization Ca++ out Myosin phosphatase Dephosphorylation of myosin relax M+A On the other hand, with repolarization, Ca++ will be removed either through the activity of the Ca++ pump on the sarcoplasmic reticulum, Ca++ pump on the sarcolemma or Ca++-Na+ antiporter. In the skeletal muscle as well as in the cardiac muscle, once Ca++ is unbound from troponin, it is expected to relax but in this case, even if Ca++ is removed from calmodulin, the vascular smooth muscle will remain contracted that is why it is capable of tonic contraction with little expenditure of energy. It will take some time before the muscle will relax by activation of another intracellular enzyme called myosin phosphatase. When activated, myosin phosphatase will cause dephosphorylation of myosin. When myosin is dephosphorylated, it will be unbound from actin and that will bring about relaxation and this is called the latch-bridge mechanism. Smooth Muscle Fiber

PHOTO: Regulation of smooth muscle myosin interactions with actin by Ca++stimulated phosphorylation. In the relaxed state, cross-bridges are present as highenergy myosin-ADP-Pi complex in the presence of ATP. Attachment to actin depends on phosphorylation of the cross-bridge by a Ca++-calmodulin-dependent myosin-lightchain kinase (MLCK). Phosphorylated cross-bridges cycle until they are dephosphorylated by myosin phosphatase. 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.

Depolarization Ca + calmodulin Myosin light-chain kinase Phosphorylation of myosin Increased ATPase M+A contraction

PHOTO: Apparent organization of cell-to-cell contacts, cytoskeleton, and myofilaments in smooth muscle cells. Small contractile elements functionally equivalent to a sarcomere underlie the similarities in mechanisms between smooth and skeletal muscle. Linkages consisting of specialized junctions or interstitial fibrillar material functionally couple the contractile apparatus of adjacent cells.

Smooth muscle is non-striated. There is no regular arrangement of the actin and myosin filaments so that when you observe the smooth muscle under the microscope, alternating thick and thin filaments and alternating light and dark bands will not be seen. The structure of a smooth muscle fiber is usually arranged in bundles. Another characteristic, there is no Z line, instead of the Z line, 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. So that force generated in one muscle fiber can be transmitted to other muscle fibers as well. Also, 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, 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. That is why the type of the smooth muscle is singleunit smooth muscle.

If the membrane is depolarized, that will allow Ca++ to enter the vascular smooth muscle cell. When the Ca++ enters, it will bind with calmodulin which will now initiate the contraction process. What happens is that the calcium-calmodulin complex will activate an intracellular enzyme that is myosin light chain kinase. When activated, myosin light chain kinase will cause phosphorylation of myosin which will then increase the activity of ATPase. With increased activity of ATPase, myosin will now form cross bridges with actin and that will bring about contraction. 3 Shannen Kaye B. Apolinario, RMT|

Attached to the dense bodies are the actin filaments and interspersed within the actin filaments are the myosin filaments. 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. When activated, 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. Differentiation of the Blood Vessels Char. 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. As to radius, the vena cava actually has a bigger radius than the aorta but the aorta has the thickest wall. Composition of the vascular wall you have elastin, smooth muscle, collagen. Elastin and collagen component is highest in the aorta but take note the smooth muscle component is most abundant in arterioles. The capillary wall has no elastin, no smooth muscle, and no collagen. As for transmural pressure, this is difference in the pressure between the inside and outside of a blood vessel and the transmural pressure is highest in the aorta, lowest in the vena cava. It is mentioned earlier that the arterial system is a high pressure area while the venous system is a low pressure area.

1 4.5 12

109 300 0.010

1010 5,000 0.004

3 x 108 4,000 0.02

18 17

2 +++

0.02 +

0.001 0

0.002 +

1.5 +

++ +++ 110

+++ + 70

0 0 20

+ + 10

++ + 5
PHOTO: Internal diameter, wall thickness, and relative amounts of the principal components of the vessel walls of the various blood vessels that compose the circulatory system. Cross sections of the vessels are not drawn to scale because of the huge range from the aorta and venae cavae to capillary.

50

0.3

0.017

0.02

4.6

Let us now differentiate the blood vessels that make up the circulatory system so you have the aorta, arterioles, capillaries, venules and vena cava. Number in the body: there is only 1 aorta, 2 vena cava superior and inferior, millions of arterioles, millions of venules, and billions of capillaries. As to cross-sectional area, you will notice that although the aorta is the biggest artery in the body, its cross-sectional area is small. Compare it to the smallest blood vessel in the body which is the capillary, it has the biggest cross-sectional area. What does cross-sectional area mean? If you put the blood vessels side by side, there is one aorta, two vena cava and billions of capillaries and if you spread all of those, which among those blood vessels would occupy the most space. When we say cross-sectional area, that is not the size of the blood vessel - you put the blood vessels side by side then spread it, 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. Correlate it with the velocity of the blood flow. When we say velocity of blood flow, that is the distance travelled by a volume of blood per unit of time. As you can see, cross-sectional area is inversely related to velocity. The aorta which has a small cross-sectional area has the highest velocity of blood flow, in contrast, the capillaries with the biggest cross sectional area has the lowest velocity of blood flow. Why did that happen? You will learn later on that again because of the closed nature of the circulatory system, 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. So if blood flow is 5L/min, in a big blood vessel like the aorta, it can easily fill up 5 L. What about the capillaries? It is small and numerous, it is slower to fill up the 5L so although the volume is the same in both, the blood flow in the aorta is faster compared to the 4 Shannen Kaye B. Apolinario, RMT|

PHOTO: Phasic pressure, velocity of flow, and cross-sectional area of the systemic circulation. The important features are the inverse relationship between velocity and cross-sectional area, the major pressure drop across the small arteries and arterioles, and the maximal cross-sectional area and minimal flow rate in the capillaries. AO, aorta; ART, arterioles; CAP, capillaries; LA, large arteries; LV, large veins; SA, small arteries; SV, small veins; VC, venae cavae; VEN, venules.

This graph will show you again the relationship between crosssectional area and velocity of blood flow. So to summarize, cross-sectional area increases from the aorta to the capillaries, it decreases from the capillaries to the vena cava. For the velocity of blood flow, it is highest in the aorta so it decreases from the aorta to the capillaries; it increases from the capillaries to the vena cava. As to pressure, again, pressure is high in the arterial system, highest in the aorta and then it progressively decreases towards the vena cava but the biggest drop in pressure is in the arterioles.

Velocity V=D T The formula for velocity is distance over time and the unit is centimetres per second. As said earlier, when we say velocity, that is the distance that is travelled by a volume of blood in a blood vessel. 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.

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, that is the measure of the degree of stretching or distensibility of an elastic structure. 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. Vascular Distensibility Which of the two will have more elastic tissue, artery or vein? Arteries have more elastic tissue and the elastic tissue is responsible for the distensibility of a blood vessel. Which is more distensible, artery or vein? It is supposed to be the artery but the arteries are 8x less distensible than the veins. 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, it can accommodate a large volume of blood compared to the artery. There are more elastic tissue in the arterial wall than in the venous wall but the venous wall is thinner. Meaning to say, if you have an artery and a vein of the same size, both can accommodate the same volume of blood but in order to stretch the arterial wall which is thick and strong, that volume of blood will exert a greater pressure or force. Compare it to the same volume of blood in the vein, whose wall is thin and also distensible so the same volume of blood will exert less force or pressure to distend the venous wall. So the venous wall being thinner that also has elastic tissue, it is more distensible, it can accommodate a large volume of blood with little increase in pressure. Arteries are 8x less distensible than the veins i.e. a given increase in pressure causes about 8x as much increase in blood in a vein as in on artery of comparable size. Veins = increase V little P Arteries = increase V higher P In the case of the veins, increase in volume but there is only little increase in pressure. In the arteries, same volume and increase in pressure. So the compliance is higher in veins.

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. The two are directly related so if the blood flow is increased, velocity is also increased. When you say velocity, again, that is the distance that a volume of blood will travel per unit of time in a blood vessel (unit: cm/s). 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). And again, the two are directly related. We already explained why velocity is inversely related to crosssectional area. Distribution of Blood Volume

PHOTO: Distribution of blood (in percentage of total blood) in the different parts of the circulatory system.

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, about 65% of the blood is contained in the venous system, 13% in the arteries, 2% in the arterioles, 5% in the capillaries, 7% in the heart and 9% in the pulmonary circulation. Vascular Compliance or Capacitance C=V P V = change in volume P = change in pressure 5 Shannen Kaye B. Apolinario, RMT|

Where:

PHOTO: A to D, When the arteries are normally compliant, blood flows through the capillaries throughout the cardiac cycle. When the arteries are rigid, blood flows through the capillaries during systole, but flow ceases during diastole.

At the top, is a normal artery or aorta. Below, you have a rigid aorta or artery. Still we are discussing compliance or stretchability of the arterial or aortic wall. A - During ventricular systole, blood will be ejected to the aorta so that the volume of blood in the aorta will increase and under normal conditions, the aortic wall will distend. At the same time, during ventricular systole, that volume of blood will be transported under high pressure to the arteries, to the arterioles, capillaries and therefore to the tissues. B - Now, during ventricular diastole (ventricles are not ejecting), the aortic wall being distensible, it can now recoil on the contained blood. And because of the recoil of the aortic wall, that will still push blood to the arteries, arterioles, capillaries and to the tissues so that means although the ejection of blood from the ventricles to the arterial system is pulsatile, the transport of blood to the tissues is continuous so there is still transport of blood to the tissues during diastole. C - What will happen if the arterial wall becomes rigid for example there is atherosclerosis which is common in the elderly. So that will make the arterial wall less distensible. During ventricular systole, blood will be ejected to the aorta, it can still be transported under high pressure to the arteries, arterioles, capillaries and to the tissues but as you can see here, it is not distended anymore. . . D - So that during ventricular diastole, because the walls are already rigid, it can no longer recoil. Nothing will push the blood towards the arteries, arterioles, capillaries and tissues so that means if the arterial wall becomes rigid i.e. atherosclerosis, that will already compromise blood supply to the tissues during ventricular diastole. Laplace equation

Large artery

Capillary

In the case of the capillary, 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. That is why the capillary wall is not prone to rupture. Compare it to a large artery, its wall is strong, 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. 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. It is equal to cardiac output and venous return so that means the average blood flow is 5,000 mL or 5L/min. Ohms Law Volume flow = Pressure Resistance According to Ohms law, blood flow is equal to pressure gradient over resistance. A B

PHOTO: Diagram of a small blood vessel to illustrate the law of Laplace: T = Pr, where P = intraluminal pressure, r = radius of the vessel, and T = wall tension as the force per unit length tangenital to the vessel wall. wall tension acts to prevent rupture along a theoretical longitudinal slit in the vessel.

T=Pr Where: T = tension on the wall P = transmural pressure (pressure inside blood vessel) r = radius of the vessel

Lets say this (above) is a blood vessel with point A and point B. So for blood to flow from point A to point B, there has to be difference in pressure between point A and point B. the greater the difference in pressure, the greater will be the blood flow so that if the pressure in point A is equal to that in point B, there will be no blood flow, it becomes stagnant. As for resistance, that is the impediment to blood flow and there are two types of resistance depending on the arrangement of the blood vessels. For example, there are blood vessels arranged in series or arranged in parallel with one another. 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. Tension is tension on the wall and pressure is inside a blood vessel. So they are directly related. How come a small blood vessel like a capillary is less prone to rupture while in large vessel i.e. artery or aorta is more prone to rupture.

resistance

P = distending pressure T = wall tension

T
6 Shannen Kaye B. Apolinario, RMT|

In in series arrangement, lets say you have an artery connected to an arteriole, connected to a capillary and then you have a venule and finally a vein. If the arteriole will constrict, resistance to blood flow will increase and so will resistance in the capillaries, venules, and vein because no blood will flow. So that means that when the blood

vessels are arranged in series, the total resistance is equal to the sum of all the resistances in individual blood vessels. Parallel: resistance

TR <

On the other hand, an artery will give rise to several arterioles arranged in parallel with one another. Each arteriole can function independently of the others so that if one arteriole will constrict, 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. The sum of all the resistances to blood flow in the systemic or peripheral circulation is what we call total peripheral resistance (TPR). Factors that will increase resistance to blood flow: Poiseuilles Equation Resistance = Length x Viscosity x 8 r4 Factors that will increase resistance to blood flow are expressed in Poiseuilles equation. So resistance is directly related to length of a blood vessel. The longer the blood vessel is, the higher the resistance to blood flow. It also related to blood viscosity. 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. In polycythemic patients, there is increase RBC production, increase RBC count, increase haematocrit that will make blood more viscous so resistance to blood flow is increased. On the other hand, the opposite is true to anaemic patients, decrease RBC count, decrease haematocrit that will make blood less viscous so that the rate of blood flow increases. Another important factor related to resistance but this time inversely related is the radius of a blood vessel and not just the radius, radius to the 4th so that will make it a very important factor. Meaning to say, during vasoconstriction, if the lumen of a blood vessel will decrease twice its normal size, that means blood flow will decrease 4x. or if during vasodilatation, the lumen or the radius of a blood vessel will increase twice its normal size, that means blood flow will increase 4x normal. So the radius of the blood vessel is very important in regulating resistance to blood flow. 2 Types of Blood Flow 1. Laminar Flow

One type of blood flow is laminar flow wherein blood flows at a constant rate. When we say laminar flow, the layer of blood that is in close contact with the vascular wall hardly moves. The next layer which is a little farther away from the vascular wall will flow at a low velocity. The next layer will move at a higher velocity. That means the highest velocity will be at the center and that will be the direction, that will be the rate along a blood vessel meaning to say, 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. 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, it creates no sound. 2. Turbulent Flow

When blood flows in different directions, 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. In the heart, the abnormal sound is a murmur; in the blood vessel it is called a bruit. What are the conditions that will predispose to a turbulent type of blood flow? 1. 2. If the velocity of blood flow increases. If the blood passes over a rough surface. Remember that endothelial lining of a blood vessel is smooth. But if there will an injury on the blood vessel wall or if there will be atherosclerotic plaques deposited on the blood vessel wall, that will make the endothelial lining rough and when blood passes over a rough surface, the direction of blood flow is disturbed. If there is an obstruction. So along a blood vessel, blood flows laminar then suddenly there is a thrombus, that will again change the direction and the rate of blood flow will be disturbed When the blood vessel makes a sharp angle, that will again predispose to a turbulent type of blood flow.

3.

4.

Reynolds Number Re = Diameter x Velocity x Density Viscosity The factors that will increase the tendency of blood flow to become turbulent are expressed in Reynolds number. The factors that are directly related to the Reynolds number are diameter of blood vessel, velocity of blood flow, and density of the fluid or medium whereas blood viscosity is inversely related to the Reynol ds number. When will turbulent flow occur? If the Reynolds number is below 2,000, blood flow is laminar and there is very little turbulence but it will easily die out. Between 2,000 to 3000 is the transition from laminar to turbulent flow but above 3000, blood flow is definitely turbulent 0 1 Velocity 2 Venous Return Volume of blood that goes back to the heart per minute 5,000 mL/min

PHOTO: When flow is laminar, all elements of the fluid move in streamlines that are parallel to the axis of the tube; the fluid does not move in a radial or circumferential direction. The layer of fluid in contact with the wall is motionless; the fluid that moves along the central axis of the tube has the maximal velocity.

Shannen Kaye B. Apolinario, RMT|

Venous return is the amount/quantity/volume of blood that will return to the heart per minute. It is equal to cardiac output and equal to blood flow so it is 5,000 mL or 5L/min. 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.

long time, there will be pulling of blood on the lower extremities. Since the venous return cannot be facilitated because of the damaged venous valves, 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. Negative intra-thoracic pressure. 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.

Venous return is equal to mean circulatory static filling pressure (MCSFP) the measure of the degree of filling of the systemic or circulatory system. Meaning to say, 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. It is actually directly related to the total blood volume (TBV). 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, 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. It is expressed as systolic pressure over diastolic pressure. 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. Why will the pressure in the aorta increase during ventricular systole? Because when blood is ejected into the aorta, the volume of blood in the aorta will increase and that will exert pressure on the aortic wall to distend the aortic wall. in the elderly, systolic pressure is usually high (higher than normal 130, 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. 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. 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, arterioles, capillaries and tissues and the aortic wall will recoil.

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. 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, you increase the tone of the venous wall that will now increase the veins vascular capacity and therefore increase venous return. So, sympathetic stimulation increase venous tone, decrease vascular capacity, and increase venous return. CVP is central venous pressure or more specifically pressure in the right atrium which is normally 0 mmHg. For venous return to increase, CVP should be lower than the pressure in the venous system. When will the right atrial pressure or CVP increase? There are factors: 1. Rate of venous return increases. 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. Pumping capacity of heart. The other factor is the pumping ability of the heart. If the pumping ability of the heart is normal, the volume of blood in the right atrium will be ejected to the right ventricle and on to the pulmonary circulation. 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. Resistance in veins. 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- 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), that will now compress the veins so the resistance in the veins will increase and that will decrease venous return. Venous pump. Other factors that may influence venous return will be the venous pump or activity of the venous valves. We all know that when you move your limbs, the venous valves will open and that will facilitate venous return. What will happen when the venous valves are damaged? When you stand for a 8 Shannen Kaye B. Apolinario, RMT|

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PHOTO: Arterial systolic, diastolic, pulse, and mean pressure. Mean arterial pressure (Pa) represents the area under the arterial pressure curve.

Pulse Pressure = SP DP Where: SP = systolic pressure DP = diastolic pressure

The difference between the systolic pressure and diastolic pressure is the pulse pressure. Again, in the elderly with atherosclerosis, what will happen to the pulse pressure? It will increase because the systolic pressure, the diastolic pressure will not change so that will now increase the pulse pressure. What about during moderate to heavy exercise? The sympathetic nervous system is stimulated so that will increase the heart rate, increase the stroke volume, and increase the cardiac output. When the cardiac output increases, the systolic pressure increases. What happens to the diastolic pressure? During exercise, with increased metabolism, there is increase heat production. Increase heat production will cause vasodilatation decreasing the total peripheral resistance (TPR). With a decrease in TPR, diastolic pressure decreases so that will widen the pulse pressure. The pulse pressure can actually be influenced by two factors: one is stroke volume greater stroke volume, increase systolic pressure, no change in diastolic pressure so that will increase the pulse pressure. The other factor is compliance of the arteries. So again, when the arterial wall becomes rigid, its compliance will decrease and that will again increase the systolic pressure, no change in diastolic pressure so that will widen the pulse pressure. Another condition is in hyperthyroidism. Thyroid hormones can directly stimulate the SA node and the myocardial cell so increase heart rate, increase stroke volume, increase cardiac output, increase systolic pressure. But at the same time, thyroid hormones can increase intracellular metabolism. Again, that will increase heat production, vasodilatation, decrease TPR, decrease diastolic pressure. So in hyperthyroidism, you have an increase systolic pressure, decrease diastolic pressure that will widen or increase the pulse pressure. So hyperthyroid patients are prone to what we call high cardiac output failure. Mean Arterial Pressure (MAP) MAP = DP + 1/3 (SP-DP) Where: MAP = mean arterial pressure DP = diastolic pressure SP-DP = pulse pressure

recoils, the volume of blood is still high and that will increase the diastolic pressure. Factors that Affect ABP To summarize, here are the factors that affect the arterial blood pressure: 1. Blood volume. How come we always say that if there is hypervolemia, there is hypertension or if there is hypovolemia, there is hypotension? If blood volume increases, that will increase initially the MCSFP. When increased, MCSFP will increase venous return. The effect of an increased venous return on the heart increases the following parameters: end diastolic volume that will stretch the ventricular wall, increase force of contraction, increase stroke volume, increase cardiac output, and increase blood pressure. Compliance of arteries. When the compliance of the arteries decreases, it increases mainly systolic pressure. Cardiac output. Increase in cardiac output will increase mainly systolic pressure. Total peripheral resistance. Vasoconstriction that will increase TPR will increase mainly diastolic pressure.

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The average pressure in the circulatory system in one cardiac system is the mean arterial pressure (MAP). Remember that this is not the average of systolic and diastolic pressure. This is the average pressure in the circulatory in one cardiac cycle. And it is equal to the diastolic pressure plus one third of the pulse pressure. Why diastolic pressure? Because 60% of the cardiac cycle is diastole, only 40% is systole. 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. If for example TPR is normal, CO increases, which will be affected more, will it be the systolic pressure or diastolic pressure? Systolic pressure because if the stroke volume increases, increase CO, increase volume of blood in the aorta that will exert a greater force on the aortic wall. Now, if the TPR increases, which will be affected more? It is diastolic pressure but why? What causes an increase in TPR? Vasoconstriction. Remember that during diastole, supposed to be there is peripheral run off blood to decrease the volume of blood in the aorta and the aortic wall will recoil. What if there is vasoconstriction? Increase TPR, blood cannot runoff to the capillaries, to the tissues etc. so there will be pulling of blood in the arterial system so that when the arterial wall

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Shannen Kaye B. Apolinario, RMT|