Cardiovascular physiology Lecture Notes General introduction 1) Circulatory system is composed of 2 units: pulmonary circulation and systemic circulation.

2) Pumping of blood to the pulmonary system is done from right ventricle and through pulmonary arteries, while to systemic circulation done from left ventricle and through aorta then through large arteries then small arteries and then arterioles and finally to capillaries (where the gas and nutrients exchange occur with tissues) and then from capillaries the venous system will begin bringing the blood back to the heart through inferior and superior vena cava. 3) Circulatory system consist of 3 parts: pumping part which is the heart, arteries which transport blood to tissues, veins which transport blood back to heart. 4) Left ventricle in larger in mass than right ventricle because it needs more pressure to pump blood through systemic arteries and for 2 reasons: a) because it need to pump blood for larger distance than pulmonary arteries b) because of total peripheral resistance which is exerted by arteries. Note: peripheral resistance is the resistance of blood vessels to the blood flow, it is dependent on (1) diameter of blood vessel (more diameter less resistance and vise versa) and on (2) distensibilty of blood vessels (meaning how much the blood vessel able to distend in response to a certain blood pressure), we have to know that arteries have distensibilty because of presence of elastic tissue. 5) Veins have more distensibilty than arteries so that they are capacitating more blood and that is because they are much thinner than arteries although they have less elastic tissue. Note: the more distensible vessel the less resistance it has, so the veins actually has very low resistance. Q. What is the larger portion of vascular system? A. When we compare large arteries if put together with small arteries if put together with arterioles if put together we will find the arterioles have largest portion of vascular system and for this they have larger portion of peripheral resistance. Note: Capillaries have no resistance because they have very thin wall (only single layer of cells).

Q. What will increase resistance? A. When the diameter of blood vessel decrease (vasoconstriction) or when the blood vessel becomes less distensible (rigid) Brief description on the heart * Consist of 2 atria and 2 ventricles; the 2 atria are separated from ventricles by a fibrous ring, which prevent electricity (action potential) to pass through them. * There is SA node (sino-atrial node) found in the right upper atrium where the superior vena cava join right atrium, this node generate frequent action potentials spontaneously to all cardiac muscle (it is called pace maker). Note: all cardiac muscle has the feature of generating and conducting action potential, but the SA node is riding the rhythm of heart because it has the following : a) Has resting membrane potential (-60) which is higher than other parts of the heart i.e. less negative than others. b) Has the feature of spontaneous depolarization rhythmically and this because of Na+ leak to inside. * When action potential generated in SA node it spread directly to both atria and the two atria behave like one unit in transmitting the current until the current reach to atrioventricular node (AV node which is special tissue present between two atria and ventricles), this node is the only way to transmit impulse down the ventricle, it has small fibers and thus the conduction of current through them is slow, that's why we consider AV node as a delay station for the impulse when it moves down to ventricles . Q. What is the benefit of presence of AV node delay? A. When AV node delay impulse to reach ventricles by this it gives enough time for atria to complete their contraction and emptying of blood to ventricles before ventricles contract, otherwise (if there is no delay both atria and ventricles will contract simultaneously and there will be no proper filling. * After AV node the impulse will be transmitted by special fibers called Bundle of His (AV bundle), which is short and will branch into 2 branches, left and right bundle branches (one for left and other for right ventricle). * These branches will branch extensively through cardiac ventricular mass to form Purkinji fibers, these fibers are large and they conduct action potential fast (actually this is the function of Purkinji fibers to speed up conduction of impulse to all ventricular

muscle the same time. * Electricity (action potential) passes through heart in access from upper right (SA node) to lower left (top of left ventricle). * So we have the following types of fibers in the heart, contractile fibers represent the mass of atria and ventricles and the conductive fibers or non-contractile fibers represent SA node, AV node, AV bundle, left and right bundle branches and Purkinji fibers. * Always remember that SA node has higher rate of firing because they has higher resting potential so they reach threshold for action potential easier and because of the spontaneous Na leak to cell which is the cause of pace maker activity. Action potential of the heart * Consist, as we know of depolarization phase caused by Na entrance and plateau phase caused by Ca entrance and repolarization phase caused by K efflux. * The plateau phase prolong the duration of action potential in heart and this has important significance in cardiac muscle contraction. Q. Why we need the plateau in cardiac action potential? A. Because the cardiac muscle is large mass and have to pump blood to all body efficiently so we need enough time for the cardiac muscle to contract efficiently so we need to prolong action potential for enough strength and duration of contraction and the plateau do this prolongation Note: we know that Ca entry causes plateau so keep in your mind that whenever Ca increase inside cardiac cell the force of contraction is larger. Note: When the venous return (amount of blood coming back to heart from tissues) increase, it will dilate ventricles and this will result in more force of contraction of the ventricles (Frank Starling law). Electrocardiogram (ECG) * It is recording of electrical events of the heart as the action potential spread from SA node down to ventricles, this action potential which is composed of depolarization and repolarization are recorded as deflections (upward and downward) by ECG machine. * When the electrical events occur in heart, little amount of electricity is transmitted to the body surface that's why we record electrical events in ECG from the body surface. * Before discussing events of ECG we have to know the cardiac electrical events which is composed of:

1) Soon after SA node fire action potential, the atria will be stimulated so they will undergo depolarization followed by contraction then repolarization follow. 2) When atria finish contraction and emptying of blood into ventricles followed by repolarization the impulse has spread to ventricles through AV node (after some delay) to give enough blood for atria to contract, then ventricles stimulated to produce depolarization then it will contract followed by repolarization during this time the atria are relaxed, after that there is a period of rest from electrical activity for both waiting for next firing from SA node. * As a summary we have the following sequence: (Atrial depolarization)..(Atrial contraction)....(Atrial repolarization) ...(ventricular depolarization)..(ventricular contraction).......(ventricular repolarization.) ECG waves You should look at the drawings of ECG waves during reading the following, ECG waves consist of P wave, QRS complex, T wave. 1) P wave: represent atrial depolarization. 2) Period between P wave and R wave (PR) represent atrial contraction. 3) QRS complex represent different ventricular parts depolarization. 4) P-R interval: represent also the delay time of AV node (the time needed for the impulse to travel from atria to ventricles). 5) Period between S and T wave (S-T segment): represent ventricular contraction. 6) T wave: represent ventricular repolarization. 7) Time between T wave and next P wave represent ventricular relaxation and filling Note: Atrial repolarization occurs during time of ventricular depolarization, and because that ventricular depolarization is larger in magnitude than the atrial repolarization (as an electrical event) so the atrial repolarization is hidden and not shown in ECG record. Notes: 1- Q wave is not always present and usually we see only RS waves but in sometimes the Q wave is very large and that indicate pathological condition in the heart (myocardial infarction). 2- You have to know that contraction means emptying of the chamber and relaxation means filling. 3- Increase Ca entry will produce more force of contraction.

4- Increasing K level will decrease firing rate of SA node (because it makes hyper polarization and less frequent firing. Mechanical events of cardiac cycle 1) Contraction and emptying a chamber is called systole while relaxation and filling of a chamber is called diastole. 2) Both atria and ventricles undergo separate cycles of systole and diastole. 3) All the events described are referred to left side of the heart because all the heart has similar events except that the pressure in right ventricle is lower. 4) We will now describe the events in cardiac cycle regarding ECG, volume changes in chambers, pressure changes and valve activity. Note: we have 2 heart sounds (S1and S2), S1 resulted from closure of AV valves (tricuspid and mitral) after ventricular systole, S2 resulted from closure of semi lunar valves (aortic and pulmonary) in the beginning of ventricular diastole. * Please refer to graphical drawing of cardiac cycle when reading the following (last page) 1) Early ventricular diastole Period of passive filling of ventricles of atria because blood from venous system still flow into atria which make atrial pressure slightly above ventricular pressure although both of them relaxed making blood pass from atria to ventricles this represented in (1) in the figure. * It corresponds to T-P interval on ECG. * During this period the blood pass to ventricles, which represent large percentage of the whole blood that will found in the ventricle after filling complete, and more than blood volume that come by atrial contraction. 2) Late ventricular diastole * During this period the SA node fire to stimulate atria which will contract to empty further blood to ventricles in ECG it is the P wave (point 3 in the figure), atrial pressure increase slightly above ventricular pressure (point 4 in figure) this blood passing to ventricles will increase the ventricular pressure (point 5) and volume (point 6). 3) End ventricular diastole * Ventricular diastole ends at the onset of ventricular contraction, when ventricular filling is complete. * The volume present in the ventricle at the end of diastole is the maximum amount of blood present in the ventricle though out the cycle and it is called end diastolic volume

(EDV), which is about 135 ml. 4) Ventricular excitation and ventricular systole * After atrial contraction is finished the impulse has spread to ventricles through AV node and special conducting system to make ventricular stimulation (QRS complex) (point 8) then the ventricular pressure start to increase (which is the beginning of ventricular systole) (point 9) so the AV valves will close because the ventricular pressure now is higher than atrial pressure and this closure will produce 1st heart sound. 5) Isovolumetric ventricular contraction * When ventricles start to contract and its pressure increase AV valves will close and the aortic valve is still closed in the beginning because the pressure inside aorta is larger so the ventricle will contract without ejection (i.e., without change in volume and this for short period) until pressure increase enough to open aortic valve and ejection of blood start (point 10) and the pressure continue to increase (point 11). 6) Ventricular ejection * When pressure inside the ventricle increase enough then the aortic valve will open (point 12) (when the ventricular pressure is more than aortic pressure) and when the blood flow though aorta it will increase aortic pressure (point 13) and in the same time ventricular volume decrease continuously (point 14). * We conclude from above that ventricular systole consist of (isovolumetric contraction and ventricular ejection). * The amount of blood volume ejected in this period is called stroke volume (SV). 7) End of ventricular systole * At the end of systole there is some of volume remain inside the ventricle and actually the amount ejected is about half of blood already present before contraction, this remained volume is called end diastolic volume and by this we can calculate the stroke volume = end diastolic volume (EDV) - end systolic volume (ESV)... SV = 135 65 = 70 ml. 8) Ventricular repolarization and onset of ventricular diastole * When the ventricles repolarize (T wave) (point 16) this occur on the end of ventricular systole and the ventricles start to relax and the pressure begin to fall until it become less than aortic and at this time the aortic valve close (point 17) producing second heart sound, this closure of the valve causes disturbance in aortic pressure making some notch

called dicrotic notch (and no more blood leave ventricles after the closure of aortic valve (point 18)). 9) Isovolumetric ventricular relaxation * When aortic valve closed the pressure inside the ventricle is still higher than that of atrium so the AV valves are also closed and by this no blood comes to ventricles or leave them and this occur while ventricles are relaxing and no change in volume (isovolumetric relaxation) (point 19 and 20). 10) Ventricular filling * When the pressure inside ventricles fall below the atrial pressure the AV valves open and ventricular filling begin (during ventricular diastole) * Notice that ventricular diastole include both (isovolumetric relaxation and ventricular filling) Notes: 1) Atrial relaxation and depolarization occur during ventricular depolarization and contraction (i.e., AV valves are closed) at the same time the blood keep flowing to atrium and accumulate there waiting for AV valves to open during ventricular diastole to pass to the ventricles rapidly and this is called (rapid filling phase). 2) When we talked about the (ventricle) we mean the left ventricle (because the same events will occur to the right one except for the pressure is lower in the right ventricle. ( 3 when blood is ejected from left ventricle to aorta during ventricular ejection the blood pressure in arterial vessels will increase to maximum and this is called (systolic pressure). ( 4 when blood ejected from the ventricle to aorta it will distend the aorta (dilate it ) and making systolic pressure , this dilation is due to presence of elastic tissue and after the ejection of blood end the aorta will recoil to resume its original size and by this it pump blood again (don't forget that aortic valve is closed ) to the systemic arteries and because of this aortic recoiling it will make what is called diastolic pressure . Cardiac out put (C.O.): * It is the amount of blood pumped from the heart per minute, it is C.O = heart rate X stroke volume, i.e. when one of them increase it will increase the cardiac out put

* Heart rate increased by sympathetic stimulation and decreased by parasympathetic stimulation * When the force of the contraction of the heart increase it will increase the stroke volume, and the force of contraction increased either by (1) extrinsic control (sympathetic stimulation) or by (2) intrinsic control (Frank-Starling law), i.e. when the venous return increase which may be caused by vasoconstriction of veins by sympathetic stimulation it will increase the amount of blood filling in the ventricle in the end of the diastole (End diastolic volume) and this will result in more force of contraction and thus more stroke volume * Dont forget that increased Ca level will also increase the force of contraction and stroke volume * In a summary; sympathetic stimulation will increase heart rate (increase C.O.) and force of contraction (increased stroke volume and C.O.) and increase venous return, which also increase the stroke volume * Keep in your mind that when CO. is increased blood pressure will increaseusually Pressure gradient: Q. What we need in order to make blood flow? A. To make blood flow between two points there must be a pressure difference between these points (pressure gradient) and blood will flow from high to low pressure Example the pressure in aorta and large vessels is greatest, while in the venous end (vena cavae and right atrium) is lowest, thats why blood flow in this forward direction Blood flow: Amount of blood volume passing through the vessel per unit time, is directlyproportional to pressure gradient in that vessel and inversely proportional to the resistance Blood flow = pressure gradient / resistance (the blood flow could be the cardiac out put)

Velocity of the blood flow: * Amount of blood flow per a distance of the blood vessel * It is inversely proportional to cross sectional area i.e. when the diameter of vessel increase for a given blood flow (constant) Resistance: * It is the opposition of a vessel to blood flow, so when the resistance increase blood flow will decrease for a given pressure gradient, and this resistance is resulted from friction of the flowing blood with the wall of the vessel Resistance depend on 4 factors : 1- viscosity of blood 2- length of blood vessel 3- radius or diameter of the vessel 4- Distensibility of the blood vessel, when increase it decrease the resistance(Distensibility decrease with aging) * When the viscosity of the blood increase the resistance increase also, viscosity is determined by the number of RBCs in the blood (hematocrit) * Usually viscosity is constant in normal persons so, it doesnt affect on resistance * When the length of the vessel increase the resistance will increase because more friction will happen between blood and the wall but also this factor is constant (not changed), so it doesnt affect resistance * When the radius of the vessel decreased it will increase resistance (inversely proportional) this factor is the most important in determining resistance (changeable) * Resistance is inversely proportional to the fourth power of the radius (i.e. the radius multiplied by itself 4 times) * So any change in radius will produce significant change in resistance Q. What is the relationship between resistance and cardiac out put? A. When the diameter of the vessel increase the resistance will decrease and vice versa, so if there is arterial vasodilatation it will decrease the

resistance and thus cardiac out put increase Q. How vasodilatation occurs? A. By the following factors; (1) increased CO2 (2) NO (nitric oxide) (3) certain substances and hormones * CO2 increase when tissue metabolism increase as to say they will dilate vessels (decreased resistance) and make more blood flow to that tissue of particular metabolism Q. What happen if the muscle is in exercise? A. CO2 will increase which will make vasodilatation and increase blood flow; also there is sympathetic stimulation, which will affect heart (the rate and stroke volume) and thus increasing cardiac out put to whole body including the muscles, also sympathetic stimulation make venous constriction and by this increasing venous return and then stroke volume and C.O. * NO (nitric oxide) is produced intrinsically by the endothelium of the blood vessel it causes vasodilatation some times called (endothelial derived factor) Pharmacological point: there is a drug called Viagra that contain synthetic nitric oxide will cause vasodilatation in blood vessels of penis used to treat conditions of impotence (difficult errection), those patients shouldnt take this drug when they are taking antihypertensive drugs because both of the drugs will reduce blood pressure Q. Why old persons develop hypertension? A. Because the blood vessels will become more resistant (atherosclerosis) and for that the blood flow will be reduced, but the heart try to pump more forcefully to keep the blood flow to organs constant Venous system: * Veins are more distensible than arteries so that they capacitate more blood than them and for that they are considered as blood reservoir * For the reason above, the veins has low resistance and therefore the blood pressure inside them is low also

Note: never forget that blood pressure is directly proportional to resistance Case discussion: if some one lost blood by bleeding lets say 1 liter his blood volume and blood pressure will decrease, how the body will compensate for that? There will be sympathetic stimulation which will result in; (1) vasoconstriction for veins to increase the venous return and so to increase the cardiac out put (2)stimulation of the heart to increase heart rate and stroke volume and both will increase the C.O. (3) vasoconstriction to arteries to increase resistance and so increasing blood pressure, all these factors will increase the blood pressure back to normal Dont forget that Pressure = cardiac out put X resistance

venous and arterial vasoconstriction (all these mediated by sympathetic), all these factors will increase the blood pressure 2) Renin angiotensin aldosteron system: * As you know that renin is released from kidneys, which will result in production of angiotensin II and secretion of aldosteron, angiotensin make vasoconstriction and aldosteron increase blood volume by increasing Na reabsorption and both effects will increase the blood pressure Notes: 1- when the blood volume increase this will increase the venous return and by this increasing C.O. and blood pressure 2- keep in your mind that vasoconstriction in veins will cause increased venous return, while in arteries will cause increased resistance and thus blood pressure Q. How to measure blood flow? A. (1) By magnetic device around blood vessel, which will detect moving particles in blood (2) By ultrasound device (sonar) which use physical phenomenon called Doppler shift Q. How to measure blood pressure (BP)? A. (1) directly by inserting a needle (a canula) to blood vessel, which is linked to a device measure the blood pressure (2) By sphygmomanometer as follow: a) When we apply a pressure by a cuff on large artery (like Brachial artery) and when this pressure is more than systolic pressure then there is no blood flow b) Then we decrease the pressure of the cuff gradually until it become like systolic pressure at this point we will hear a turbulent blood flow by the stethoscope applied on the artery then we know that this level of pressure in the cuff is equal to systolic pressure c) And then we continue decreasing the pressure inside the cuff until the turbulent flow sound disappear , and at this point of pressure present inside the cuff when the sound disappear it is the value of the diastolic pressure

Q. How venous return is controlled? A. By the following: 1) Venous valves: they allow the blood to flow in one direction toward heart only * When the skeletal muscles contract in normal body activity they compress on the neighboring veins that lie near by them and thus squeezing them to push blood toward heart only because of the presence of venous valves 2) Sympathetic stimulation, which causes vasoconstriction to veins 3) Respiration: as we know that there is negative intrathoracic pressure (intra pleural) which is changing in respiratory cycle and that help in pumping blood through the veins that lie inside thoracic cage Regulation of blood pressure: controlled by:

1) Baroreceptors; in aortic arch and carotid sinus, if blood pressure decreased the baroreceptor will send information to brain stem where the cardiovascular centers, these centers will make reflex increase in heart rate, force of contraction

Note :there are two types of blood flow: 1- Laminar flow: when the fluid molecules slide smoothly in one direction and there is no sound associated with the flow 2- Turbulent flow: when the molecules of the fluid move in more than one direction and not smoothly and there is a sound associated with the flow, and this occur as a result of narrowing or stenosis of the vessel (example in atherosclerosis plaque ) * When we examine an old man patient we suspect that he has atherosclerosis and thats why we put the stethoscope on the neck (carotid arteries) to hear if there is any turbulent flow Definitions: 1- pulse pressure = systolic pressure diastolic pressure 2- mean arterial pressure = diastolic pressure + 1/3 (pulse pressure)