Physiology of Cardiovascular System PDF

Physiology of Cardiovascular System 1 he Cardiovascular System Heart: a double sided pump that establishes blood pressure, needed to get blood flow out to the tissues. Blood Vessels: passageways for blood to be distributed throughout the body a...

Physiology of Cardiovascular System 1 he Cardiovascular System Heart: a double sided pump that establishes blood pressure, needed to get blood flow out to the tissues. Blood Vessels: passageways for blood to be distributed throughout the body and exchange materials to/from the tissues Blood: liquid connective tissue that 2 ) Physiology of Heart The heart is a large muscle forms a double-sided pump – 1) pumps blood to the lungs and blood from the lungs – 2) pumps blood to the body and receives blood from the body made up of cardiac muscle, and cardiac nervous tissue, with protective epithelial and connective tissues 3  2 Circulatory Pathways Pulmonary Circuit: heart to lungs, lungs back to heart – Replenishing circuit: blood from right side of the heart is low oxygen, high carbon dioxide blood travels to the lungs, picks up oxygen, removes carbon dioxide oxygenated blood returned to the left side of heart Systemic Circuit: heart to body tissues, body tissues back to heart – Delivery Circuit: oxygenated blood pumped out of left side of heart delivered to tissues for metabolic functions metabolism uses up oxygen, gives off carbon 4  Pulmonary and Systemic Circulatory Pathways Right Right atrium ventricle Venae Pulmonary cavae artery Other systemi Digestiv Systemic Pulmonar Brai Kidney Muscle Lungs c e circulatio y n s s organs tract n circulatio n Aort Pulmonary a veins Left Left (b) Dual pump action of the ventricle atrium heart 5 Fig. 9-2b, p.  Pathway of Blood through Heart Aort a Superior vena Pulmonary cava artery Pulmonary (SL) valve Pulmonary veins Left Pulmonary atrium veins Left AV, BV, Mitral Right valve atrium Aortic (SL) Right AV, TV valve Chordae valve tendineae Papillary muscle Left ventricle Right ventricle Inferior vena Interventricul cava ar septum 6 (a) Location of the heart valves in a longitudinal section of the Fig. 9-4a, p.  Pathway of Blood through Heart Starting at the right side: Deoxygenated blood returns via the SUP/INF VENA CAVA to RIGHT ATRIUM, through tricuspid valve, into right ventricle Deoxygenated blood pumped out of RIGHT VENTRICLE, through pulmonary semi-lunar valve, into PULMONARY TRUNK to the pulmonary arteries, to the lungs Oxygenated blood returns to heart via pulmonary veins to LEFT ATRIUM, through the bicuspid valve, into the left ventricle 7 Oxygenated blood pumped out of LEFT VENTRICLE  Heart Valves 4 valves ensure one-way flow of blood through the heart: – Atrio-ventricular valves: Tricuspid & Bicuspid Valves located between the atria and ventricles open for blood flow into ventricles, when atrial pressure exceeds ventricular pressure closed during pumping of ventricles, when ventricular pressure is high Choradae tendinae & papillary muscles prevent valve eversion (flipping backwards) – Semi-lunar valves: Pulmonary SL and Aortic SL located in the pulmonary trunk and aorta open during ventricular pumping to allow blood 8  Heart Valves When pressure is greater behind the valve, it opens. Valve opened When pressure is greater in front of the valve, it closes. Note that when pressure is greater in front of the valve, it does not open in the opposite Valve closed; does not direction; that is, it is a open one-way valve. in opposite direction 9 Fig. 9-3, p. Right atrium Right AV Chordae valve tendineae Direction of backflow Septu of m Right blood ventricle Papillary muscle (c) Prevention of eversion of AV valves 10 Fig. 9-4c, p.  Cardiac Muscle Cells Cardiac muscle is striated (contains actin and myosin) and branching Adjacent cells connected by intercalated discs, which contain: – Desmosomes: mechanically hold cells together as heart contracts – Gap Junctions: electrically connect cells 11  Plasma membranes of Desmosom adjacent cardiac muscle e fibers Gap Action junction potential Intercalated disctwo types of (b) Intercalated discs contain membrane 12 junctions: mechanically important desmosomes Fig. 9-6b, p.  Functional Syncytium Because regions of the heart are connected electrically by gap junctions, they form a “functional syncytium” – when one cell undergoes an action potential, the AP spreads to all connecting cells, they all contract together 13  The Intrinsic Conduction System The heart has electrical activity AV Node independent of the SA Node nervous system Action potentials in the heart are generated by the intrinsic conduction system, a set of electrical pacemaker cells Purkinje fibers 1. SA Node 2. AV Node Bundle of His 3. Bundle of His (AV Bundle) 14  SA Node The SA Node is located in the AV Node SA Node upper right atrium Fastest, sets the pace of the heart 70 – 80 action potentials per minute at rest Activity spreads to Purkinje fibers BOTH atria and to the AV Node Bundle of His 15  AV Node The AV Node is located in the lower AV Node right atria, near the SA Node ventricular septum 2nd fastest, only sets the pace if there is damage to the SA Node 40-60 action potentials per minute Purkinje fibers Activity pauses first, then spreads to Bundle of His Bundle of His AV Nodal Delay , 16 due to fibrous tissue,  Bundle of His & Purkinje Fibers The Bundle of His is located within the AV Node interventricular SA Node septum, and has a right and a left branch The Purkinje Fibers travel up the outer walls of the ventricles 20-40 action potentials per minute Purkinje fibers activity spreads to ventricles Bundle of His 17  Electromechanical Properties of Heart Cardiac function is not fully dependent on intact nervous pathway. Heart continues to beat after full denervation, because of its intrinsic properties. A. Automaticity B. Conductivity C. Contractility D. Refractoriness A. Automaticity (myogeny): – 1. Act as a pacemaker, setting the rhythm of electrical excitation that causes contraction of heart. – 2. Highly developed in nodal tissues but observed in any piece of cardiac tissue. Inherent rates: SA node =70-80 bpm, AV node =60-65 bpm Atria = 60-65 bpm, Ventricles =30-40 bpm 18  Conductivity and Contractility B. Conductivity: From conduction system, a network of specialized cardiac muscle fibers that provide a path for each cycle of cardiac excitation to progress through the heart. – Most highly developed in Purkinji network, which is weakly contractile. – Conduction velocity is 6 times that of the rest of myocardium. C. Contractility: – Atrial and ventricular muscles are contractile muscles. Highly specialized for contraction. Follow ALL-or-NONE response pattern. 19  Refractoriness D. Refractoriness – Cardiac cell is unresponsive to further stimuli. – During the phase of contraction, heart is unexcitable (refractory) to stimulation. – Normal refractory period of ventricle is 0.25 – 0.30 sec. There are two degrees of refractoriness: – 1. Relative refractoriness: Only APs of smaller amplitudes and rates of rise can be generated (strong stimulus). – 2.Absolute refractoriness. No other AP can be triggered, even by extremely strong 20  Primary pacemaker SA node is the primary pacemaker due to following findings: – 1. First region to display electrical activity is SA node. – 2. Crushing and localized cooling of SA node leads to bradycardia. – 3. Application of drugs and humoral agents to SA node leads to alteration of heart rate (HR). 21  SA node as Pacemaker Cardiac excitation begins in sinoatrial (SA) node. – SA node have no stable resting potential. – The spontaneous depolarization is a pacemaker potential. – Pacemaker potential reaches threshold it triggers an action potential. – Following the Action potential, atria contract. – Connects directly with atrial muscle fiber. Have no contractile muscle filaments. SA node initiate an AP – ANS and hormones modify timing and strength of heartbeat. In Resting person. – Ach released by parasympathetic nerves slows SA node 22  Mechanism of Sinus Nodal Rhythmicity Cardiac muscle have 3 types of ion channels – 1. leaky Na+ channels – slow upstroke spike of AP. – 2. Voltage gated Ca2+ channels – rapid depolarization. Also called as slow Na+ - Ca2+ channels. Activatation make SA node self excitatory. – 3. Voltage gated K+ channels – return to RMP by rapid repolarization. 1. Due high Na+ con on outside, Na+ ions leak into SA node by leaky Na+ channels. – Leads to slow raise of RMP (-60 mV to -55mV) to Threshold Potential (-40 mV). 2. Voltage gated Ca2+ channels become “activated”. – Ca2+ channels closed. – At the same time, open large no of voltage gated K+ channels. 3. Large quantities of positive K+ ions diffuse out of fiber. – Both of these effects reduce intracellular potential back to its negative 23 resting level and terminate AP (-60 mV to -55mV).  24 Fig. 9-7, p.  Mechanism of Sinus Nodal Rhythmicity 4. Opening of voltage 3. Ca2+ dep Depolarization dep K+ channels 2. Opening of voltage gated Ca2+ channels Th P RMP 85- 90 mV 1. Opening of leaky Na+ channels In Sinus nodal fiber “resting” potential is much less negative only -60 mV in nodal fiber instead of -90 mV in ventricular muscle fiber. At -55 mV fast Na+ channels already become “inactivated,”. 25 Only slow Na+channels open (activated) and cause AP.  AP of AV node – AV node specialized in slow conduction. Depend on voltage gated Ca2+ channels. AV node cells are smaller in size. Few gap junctions. RMP is – 60 mV Voltage gated Na+ channels not function. Only functional channel is voltage gated Ca2+ channel. 26  AP of AV bundle From AV bundle, AP enters both right and left bundle branches to ventricle. – The bundle branch pass through interventricular septum towards apex of heart. – Specialized in fast conduction. The A-V bundle divides into L and R bundle branches that lie beneath the endocardium on two respective sides of ventricular septum. The total time for transmission of cardiac impulse from initial bundle branches to last of ventricular muscle fibers in normal heart is about 0.06 second. 27  Purkinje cells Finally, large-diameter Purkinje fibers conduct AP beginning at apex of heart to remainder of ventricular myocardium. Specialized conductive tissue of heart for fast conduction system. – Purkinje cells are broad cells (70-80 µm in diameter) compared with ventricular myocardial cells (10-15 μm in diameter). – Cells are arranged in along the axis of current flow. – Gap junctions are more. – Diameter of cell is more. – RMP is – 90 mV The ventricles contract, push the blood upward to SL valve. 28  Role of Vagal Effects in AP. Stimulation of vagal nerves secrete Ach gives two effects. – Decreases the rate of rhythm of sinus node. – Decreases the excitability of A-V junctional fibers between the atrial musculature and A-V node. Slowing transmission of cardiac impulse into ventricles. – The Ach acting on cell membrane of SA node makes the membrane more permeable to K +. This produces two effects: – 1. Repolarization or resting membrane potential. – 2. Reduction in the rate of formation of pre-potential. These conditions lead to longer time for the Pre-potential to reach threshold thus making HR slower 29  Action Potential of Cardiac Muscle The AP initiated by SA node travels along conduction system and spreads out to excite the “working” atrial and ventricular muscle fibers, called contractile fibers. Cardiac muscle AP have three phases. – 1. Depolarization phase. – 2. Plateau phase. – 3. Repolarization phase. 30  Action potential in contractile fiber Fast Na+ channels closed Some K+ channels open T.P -70 mV -90 mV R.M.P The presence of plateau in action potential causes ventricular contraction to 31 last as much as 15 times as long in cardiac muscle as in skeletal muscle.  Depolarization The RMP of contractile fiber is -90 mv. When a contractile fiber is brought to threshold by an AP, from neighbouring fibers, its voltage gated fast Na+ channels open. Inflow of Na+ down the electrochemical gradient produces a rapid depolarization. – Within a few milliseconds, the fast Na+ channels automatically inactivate and Na+ inflow decreases. – Resting potential changes from -90mV to +30 mV. Then early partial re-polarization caused by opening of voltage gated K+ channels. 32  Plateau Phase A period of maintained depolarization, opening of voltage-gated slow Ca2+ channels in sarcolemma and Sarcoplasmic reticulum. – Also called as slow Ca2+ - Na+ channels. – When these channels open, Ca 2+ ions move from interstitial fluid into cytosol. – Increased Ca2+ concentration in cytosol triggers contraction. Before plateau phase begins, some voltage gated K+ channels open, allowing K+ to leave contractile fiber. – Depolarization is sustained during the plateau phase because Ca2+ inflow just balances K+ outflow. – The plateau phase lasts for 0.3sec. 33  Repolarization The recovery of RMP during repolarization phase of cardiac AP resembles excitable cells. After a delay more voltage-gated K+ channels open. Outflow of K+ restores the negative RMP (- 90 mV). Ca2+ channels in sarcolemma and SR are closing, remove Ca2+ form cytosol, contributes to repolarization. 34 Ca2+ signaling in cardiac muscle Excitation-Contraction Coupling Affected by epinephrine () and 1 Ca2+ out ACh () of Ca2+ Entry for 3 Na+ during action in potential 35  Electrocardiogram (ECG) and Cardiac cycle 36  Electrocardiogram (ECG or EKG) The ECG is a composite record of AP produced by heart muscle fibers during each heart beat. – Recording of voltage of beating heart at the surface of body. – Measurement of vector ( have both force and direction). The instrument used to record the changes is Electrocardiograph. – ECG of heart is recorded from specific sites of body in graphic form relating voltage (vertical axis) with time (horizontal axis). – Waves – Produced due to fluctuation of needle during ECG recording. 37  Application of ECG The Electrocardiograph used for – 1. Detect the abnormality in conducting pathway. – 2. Detect the enlargement and damaged regions of heart. – 3. Detect the cause of chest pain. By analyzing electric potential fluctuations, physician can get some insight into – Determination of Heart rate, – Relative size of heart chambers, – A variety of disturbances of rhythm, conduction arrhythmia and conduction block, – Location and progress of ischemic damage (myocardial infarction) 38 – Hypertrophy, Pericarditis and myocarditis. Heart Excitation Related to ECG 39 40  Direction of depolarization 4 1 4 5 2 4 3 4 41 Vectorial Analysis Summary 42 ECG Machine How Many leads and electrodes are There in 12 – lead ECG? What is the d/ce b/n lead and 43 Electrocardiographic Leads Three types of electrocardiographic leads. 1. Standard bipolar limb leads. 2. Augmented unipolar limb leads. – aVR, aVL and aVF. 3. Precordial chest leads. – V1, V2, V3, V4, V5 and V6. 44  Electrocardiographic Leads Standard bipolar limb leads. Two electrodes located on different sides of heart, in this case on limbs. The “lead” is not a single wire connecting from body but combination of two wires and their electrodes to make a complete circuit between body and electrocardiograph. 45 With respect to average  Standard bipolar limb leads Recorded from two electrodes located on different sides of heart, in this case, on limbs. – Record voltage between 2 electrodes (leads) placed on wrists and legs. Lead I. – Negative terminal of ECG connected to RA and positive terminal to LA. Electric potential difference b/n Left arm & Right arm. Lead II. – Negative terminal of ECG connected to RA and positive terminal to LF. Electric potential difference b/n Left leg & Right arm. Lead III. – Negative terminal of ECG is connected to LA and positive terminal to LF. Electric potential difference b/n Left arm & Left leg. 46 47 Chest Leads (Precordial Leads) QRS in V1, V2, are negative because chest electrodes are nearer the base of the heart (direction of electronegativity). V3 is in between electronegative and electropositive – biphasic. QRS of leads v4-v6 are positive because they are nearer the apex (direction of electropositivity). 48 Voltage and Time Calibration of ECG Horizontal calibration lines are arranged 10 of small line divisions upward or downward in standard electrocardiogram is 1 mV. 1 inch in vertical direction is 1 second and each inch is divided into 5 dark vertical lines. – Intervals between these dark lines represent 0.20 second. – The 0.20 second intervals are again divided into 5 smaller intervals by thin lines by 0.04 second. – Paper speed 25mm/sec or 300 big sq/min. 49  Electrocardiograph Atria Ventricles – Cardiac AP arise from SA node, at 0.04 sec P wave appears in Ventricular ECG. Depolarization P wave for Atrial / SA Atrial Ventricular Repolarization node depolarization. Depolarization – Spreads from SA node through contractile fibers in both atria. – Speed is moderate velocity. – About 0.2 sec after onset of P wave, AP enter into AV bundle Atrial repolarization record is masked by larger QRS complex. 50  Electrocardiograph QRS complex for rapid Ventricular depolarization. (3 steps) – The AP spreads through ventricular contractile fibers. 1. Ventricular septal depolarization. 2. Major ventricular depolarization towards apex. 3. Basal ventricular depolarization. – After 0.2 sec onset of P wave, Depolarization of ventricle produce QRS complex. T wave indicates ventricular repolarization (recover from depolarization). (0.4 sec after onset of P wave) – Repolarization of ventricular contractile fibers begins at apex and spreads throughout the ventricular myocardium. – By 0.6 sec, ventricular repolarization is complete and ventricular contractile fibers are relaxed. Next 0.2 sec, contractile fibers in both atria and ventricles relaxed. 51 nterval and segments P-Q interval – Time required for AP to travel through atria, AV node and remaining fibers of conduction system (upto Apex). P-R segment (End of P wave and when Q wave absent) – Duration of current is held in AV node. P-R interval (starting from P wave) – Atrial depolarization and AV nodal delay (0.16 sec). – Longer P-R interval is AV node block. Normal R-R interval is 0.83 sec HR = 60/R- R interval. S-T segment, – Ventricular fibers completely depolarized during plateau phase of AP. Q-T interval. – Beginning of ventricular depolarization to end of ventricular repolarisation. U wave – Electrical activity of papillary muscle. 52  Cardiac cycle Events that occur in one complete heart beat. – One complete sequence of contraction and relaxation of all four chambers of heart. – Each cycle is initiated by AP of Sinus node. – When heart beats, 2 atria contract together, 2 ventricles contract together and both relaxed. – Systole is contraction phase of cardiac cycle. Contraction of atria and ventricles. – Diastole is relaxation phase of cardiac cycle. Muscle fiber lengthening and filling of atria and ventricles. Coronary perfusion occurs. 53  Events of Cardiac Cycle Electrical events of summated ECG voltage changes: – P wave, – QRS complex, – T waves. Mechanical events of : – Myocardial systole and diastole. – Opening and closing of cardiac valves. – Pressure changes. – Volume changes. – Heart sounds. 54  AV valve open All valves are closed 5 SL valve closed Dubb AV valve closed 80 Lubb 120 All valves are 8 - 25 120 closed SL valve open 55  Cardiac cycle of left ventricular function RPVFSPVF A.C SEP Left Ventricular pressure REP Mitral Mitral close open Left atrial pressure Time scale S3: Audible in children and in adults during exercise (During rapid filling). 56 S4:Caused by rapid ventricular filling during atrial systole (hypertropied heart).  Atria as Primer Pumps Atrial diastole – R. Atria receives blood from SVC & IVC. – L. Atria receives blood from Pulmonary veins. Atrial systole – 80% of blood flow from veins directly reach ventricles through atria. – Atrial contraction causes an additional 20% filling of ventricles. However heart can work without 20% of filling, because it has capacity of pumping 300 to 400 % more blood than is required by the resting body. – The atria fail to function only at the time of exercise or physically active. (shortness of breath) That’s why persons with atrial fibrillation survive for many years without any circulatory problem. 57  Pressure Changes in the Atria Three minor pressure curve for atria. a wave – when atria contracted. – RA pressure increases to 4-6 mm Hg and LA pressure increases to 7-8 mm Hg. c wave – When ventricles starts contracted. – Slight backflow of blood into atria at onset of ventricular contraction but mainly by bulging of A-V valves. v wave – Occurs at end of ventricular contraction. – Slow flow of blood into atria from veins while A-V valves are closed during ventricular contraction. A cardiac AP arises in SA node. – During atrial depolarization, P wave appears in ECG. – After P wave begins, the atria contract (0.1 sec). End of atrial systole is the end of ventricular diastole (relaxation). End of ventricular diastole each ventricle contains 110 - 120 ml of blood called end-diastolic volume (EDV). 58  Ventricular systole and diastole Ventricular systole. 1. Isovolumetric Contraction Period (IVC). 2. Ventricular Ejection. – Maximum ejection period (REP). – Reduced ejection period (SEP). Ventricular diastole. 1. Isovolumetric relaxation (IVR). 2. Filling phase 59  Isovolumetric contraction – Atrial systole fills ventricles. Contraction of ventricular contractile fibers begins shortly after QRS complex appears and continues during S-T segment. – Ventricular depolarization causes ventricular systole. – 0.05 sec both SL valves and AV valves closed. – Closure of A.V Valves produce 1st heart sound (Lubb). During this period, tension is increasing in muscle but little or no shortening of muscle fibers is occurring. – but no emptying only Intraventricular pressure rises. – This is the period of isovolumetric contraction. 60  Ventricular Ejection Continued contraction of ventricles causes pressure inside the chambers to rise sharply. L. ventricular pressure raise above 80 mmHg upto 120 mmHg. – The SL valves are open is ventricular ejection last for 0.25 sec. Immediate opening of SL valves cause Maximum ejection of blood (70%). It is called as Maximum ejection period or Period of Rapid ejection. Period of slow ejection (30%). When some blood is moved out, the rate of ejection becomes slower. Hence it is called as Reduced ejection period or Period of slow ejection. R. ventricular pressure slightly above 8 mm Hg -25 mmHg. Ejection of blood causes increase pressure in aorta and pulmonary artery. – Decrease Intraventricular Pressure. – Closure of SL valves produce 2nd heart sound (Dubb). 61  Ventricular- end systolic volume Left and R. ventricle ejects 70 mL of blood into aorta and pulmonary artery. – The volume remaining in each ventricle at end of systole, about 50 ml, is end- systolic volume (ESV). Stroke volume. – The volume ejected per beat from each ventricle. – Equals end-diastolic volume minus end systolic volume. SV = EDV - ESV. 120 ml - 50 ml = 70 ml (SV). – T- wave marks onset of ventricular repolarization. 62  Isovolumetric relaxation Atria and the ventricles are both relaxed. – Ventricular repolarization causes ventricular diastole. – Ventricles relax - pressure decreases – blood from aorta and pulmonary trunk cause back flow, which close SL valves. – SL valves close, ventricular blood volume does not change because all four valves are closed This period is called isovolumetric relaxation. When ventricular pressure drops below atrial pressure, the AV valves open and ventricular filling begins. 63  Ventricular Diastole A-V valves closed, blood accumulate in R and L atria. After atria filled by blood, push A-V valve open allow blood to flow rapidly into ventricles. – Cause rise of left ventricular volume curve. Period of filling of ventricles divided into three parts. Period of rapid filling. (Rapid Passive Ventricular Filling) – Pressure gradient blood rushes rapidly from atria into ventricles. – About 75 % filling occurs due to pressure gradient only. small amount of blood normally flows into ventricles. (Slow P V F) – It is other wise called as Diastasis – (from veins to ventricles) No flow phase. atria contract give additional thrust to inflow of blood into ventricles. – 20 % of the filling of ventricles during each heart cycle. 64 – Next cardiac cycle begins with P wave. Summary of cardiac cycle 65  Ventricular volumes Ventricular end diastolic volume (VEDV). – Volume of blood in ventricle at the end of ventricular diastole (relaxation phase) EDV = 110 - 120 ml. Ventricular end systolic volume (VESV). – Volume of blood that remains in ventricle at the end of ventricular systole (contraction phase). ESV = 40 - 50 ml. Stroke volume output (SV). – Volume of blood ejected from ventricle during ventricular systole. – (stroke volume) SV = EDV – ESV = 70 ml. Ejection fraction: Fraction of end-diastolic volume that is ejected EF = SV/EDV = 60%. 66  Heart Valves and Heart Sounds Closing of valves causes audible sounds but opening of valves not produce any sound. – “Lub” is associated with closure of A-V valves at beginning of V. systole. (1 st sound) The first sound about 0.14 second. – “Dub” is associated with closure of SL (aortic and pulmonary) valves at the end of V. systole. (2nd sound). SL valves are more rigid than AV valves. The second about 0.11 second. Greater elastic coefficient of tight arterial walls provide principal vibrating chambers sound. Sound due to – When AV valves close, Vibration of taut valves immediately after closure, along with vibration of adjacent walls of heart and major vessels around heart. – When SL valves close, they bulge backward toward ventricles and their 67 elastic stretch recoils blood back into the arteries.  Phonocardiograms Normal and murmurs Systolic Murmur of Aortic Stenosis. – Blood is ejected from left ventricle through only a small fibrous opening of aortic valve. – Sound heard in upper chest and lower neck called “Thrill” Systolic Murmur of Mitral Regurgitation. – Blood flows backward through the mitral valve into L. atrium during systole. Diastolic Murmur of Aortic Regurgitation. – No abnormal sound is heard during systole, but during diastole. Diastolic Murmur of Mitral Stenosis. – Blood passes with difficulty through the stenosed mitral valve from L. atrium68into the L. ventricle.  Analysis of Ventricular Pumping Diastolic pressure curve is determined by filling heart with greater volumes of blood. Systolic pressure curve is determined by recording systolic pressure achieved during ventricular 5 mm Hg contraction at each volume of filling. – R. Ventricle Systole Pressure is 60- 80 mm Hg. 69 Volume-pressure  volume-pressure diagram of the cardiac cycle Phase I – Period of filling. – Ventricular volume is 45ml (ESV) and diastolic pressure is 0 mm Hg. – Ventricular volume increase to 115 ml (EDV). – Diastolic pressure increase to 5 mm Hg. Phase II – Period of isovolumic contraction. – No change in ventricular volume (All valves closed). – Pressure inside the ventricle increases to pressure in aorta (80 mm Hg). Phase III – Period of ejection. – Systolic pressure rises higher due to more contraction of ventricle (120 mm Hg). – Volume of ventricle decreases because aortic valve has opened and blood flows out of ventricle into aorta. Phase IV – Period of isovolumic relaxation. – At the end of period of ejection, aortic valve closes and ventricular pressure falls back to diastolic pressure level. – The ventricle returns to its starting point, with about 50ml of blood left in ventricle and at an atrial pressure near 0 mmHg. 70  Cardiac Output (CO) CO is volume of blood pumped by each ventricle in 1 min to pulmonary and systemic circulation. CO is product of heart rate (HR) and stroke volume (SV). – CO = Stroke volume X Heart rate – SV is amount of blood pumped out by ventricle each beat. (70 ml/beat). – HR is number of heart beats per minute. (75 beats / minute). – CO = 70 X 75 ml / min = 5250 ml/ min = 5.25 L / min. – CO always equals the venous return. – CO determined by venous return. 71  Stroke volume Stroke volume (SV) = EDV – ESV. To increase stroke volume Increase EDV – Increase venous return Increase blood flow by decrease resistance (F = ∆P/ R). – Increase ventricular compliance Decrease ESV – Increase contractility – Decrease after load. Three factors regulate the stroke volume. – 1. Preload/ VR/ EDV (effect of stretching). – 2. Myocardial Contractility. – 3. After load (effect of contracting). 72  Effect of preload Preload (based on Frank – Starling law). Length tension relationship of cardiac muscle. Stretched muscle contracts more forcefully than outstretched muscle. – Volume of blood reach the ventricle at the end of diastole (EDV). After passive (80%) and active filling (20%). – VR increased – EDV increased– more forceful the next contraction. – Increase SV leads to increase in CO. – Pressure during filling of ventricle. – Change in EDV – Change in myocardial stretch – change in myocardial contractility – change in strove volume (Ejection fraction). – Heart rate is inversely proportional with EDV. 73  Frank-Starling Law of the Heart Intrinsic ability of heart to adapt to increasing volumes of inflowing blood. Diastolic filling of heart is directly proportional with displacement of heart muscle. – Greater the heart muscle is stretched during filling →↑force of contraction →↑blood pumped to aorta. – More the heart fills, greater the force of contraction. – Preload or degree of stretch, of cardiac muscle cells before they contract is the critical factor controlling stroke volume. Depends on EDV. – Exercise increases venous return to the heart, increasing EDV→↑ SV. – Blood loss and extremely rapid heartbeat (decreases ventricular filling time and decreasing EDV) →↓SV. 74 Frank-Starling Law 75  Contractility – Effect the contractile force of ventricular myocardium. Positive ionotropic agent (Increase SV). Increase Heart rate. Increase AP. – More Ca2+ enter the AP. Sympathetic stimulation – Norepinephrine – stimulate B1 receptors. – Increase the activity of Ca2+ pump. – Concentration of intracellular Ca2+ in SR. Cardiac glycosides (digitalis). – Inhibit Na+ - K+ ATP ase – increase intracellular Ca2+. Negative ionotropic agent (decrease SV) Increased K+ level in interstitial fluid. Parasympathetic stimulation – Decrease intracellular Ca2+ 76 Effect of contractility in Frank starling law 77  Effect of After load Afterload - (increase Total Peripheral resistance) Pressure in ventricles causes blood to push SL valves open. The pressure that must be overcome before a SL valve can open is termed afterload. Arterial pressure against which the ventricle contract. – Pressure exerted by blood in large arteries leaving the heart. Increase afterload due to increase hypertension or atherosclerosis. Afterload inversely proportional with cardiac output. 78 Preload and After load 79  Effect in volume pressure curve. Preload increase EDV, increase SV , increase pressure volume curve. After load decrease stroke volume, decrease pressure volume curve 80 and increase ESV.  Heart Rate HR is the number of cardiac cycles per minute – Normal HR: 60 to 100 beats/minute. – Resting person HR is 75 b/min. < 60 beats/minute, bradycardia but normal in athletes. > 100 beats/minute, tachycardia. (upto 250 b/ min). HR varies with the following factors – Age: Higher in newborn infants (120 b/min) gradually with childhood. – Sex: Higher in females (85 b/min). – Time of the day: ↓morning, ↑evening. – Resting and sleep: Decreased. – Physical training: low in athletes (45-60 b/min). – Body position: ↑standing, ↓supine positions. – Temperature : Temperature ↑ HR ↑ (During fever). How to count HR – Counting arterial pulsation, heart sound and ECG cycles. 81  Heart regulation – Adjustment in HR important in short term control of CO and BP. Tissues require different volumes of blood flow under different conditions. During exercise, hemorrhage, decrease SV in myocardial damage. There are 3 primary properties regulated within heart. – All properties have both positive and negative effects. – They can increase HR to 4 - 5 times. 1. Chronotropic properties (Refers to heart rate). 2. Dromotropic properties (Refers - speed of conduction). 3. Inonotropic properties (Refers – force of contraction). 82  Heart Regulation Intrinsic regulation – Increase Venous blood return to R. Atrium. – Cause SA node to stretch, leads to SA node depolarized faster – Increase blood to R. Atrium cause increase HR. This is called as bainbridge reflux. Extrinsic regulation (ANS) – Parasympathetic nervous system signals via vagus nerves – decreased HR and force of contraction. Affect both chronotropic and ionotropic properties. – Sympathetic nervous system signals via T1- T5 in spine, effect chronotropic and dromotropic properties of heart. 83 Result in effecting ionotropic properties.  Effect of sympathetic nervous system Sympathetic (HR 250 > 100 b/ min). Release more Norepinephrine (NE) than Epinephrine (E). NE binds to beta-1 receptors on cardiac muscle fibers cause two effects. – 1. In SA and AV node fibers, NE speeds the rate of spontaneous depolarization. Which fire impulses more rapidly and HR increases. – 2. In contractile fibers, atria and ventricles, NE enhances Ca 2+ entry through voltage-gated slow Ca2+ channels, thereby increasing Contractility. (greater ejection during systole) When stimulated – Increasing volume of blood pumped and increasing ejection pressure. Increase the maximum cardiac output. When depressed – Decreases both HR and strength of ventricular muscle contraction.84  Effect of parasympathetic nervous system Parasympathetic Nerves (Vagus) (HR < 20 b/ min). – Vagal axons terminate in SA node, AV node and atrial myocardium. – Released Ach cause hyperpolarization of SA node. – Decreases HR by slowing the rate of spontaneous depolarization in autorhythmic fibers. – Negative chronotropic Na+ during depolarization. – Negative dromotropic effect due to Ca2+ and K+ Has no or little effect in contractility of ventricles. – When parasympathetic stimulation continues it leads to heart beat at the rate of 20 to 40 b/ minute. – Decrease strength of heart muscle contraction by 20 to 30 %. 85  Nervous system control of heart. Medulla oblongata Thoracic region Release Adrenaline Enhances Ca2+ entry through voltage-gated slow Ca2+ 86 channels  Chemical Regulation of Heart Rate Hypoxia, Acidosis (low pH) and Alkalosis (high pH) all depress cardiac activity. 1. Hormones. Epinephrine, Nor epinephrine and Thyroid. Enhance cardiac contractility and increase HR. 2. Cations – Elevated blood K+ decrease HR and contractility. Excess Na + blocks Ca2 + inflow during cardiac AP, force of contraction. – whereas excess K+ blocks generation of AP. Dilation of heart, flaccid and slow the heart rate. Cause weakness of heart and abnormal rhythm leads to death. – Moderate interstitial Ca2+ level speeds HR and strengthens HB. – Excess calcium ions. - Spastic contraction of heart muscles. – Deficiency of calcium leads to 87 Cardiac flaccidity – similar to the effect of high K+ ions.  Role of SA node in Regulating HR HR is determined by the rate of discharge of impulse from SA-node. Following factors affect SA node directly or indirectly. – Factors that directly stimulate SA-node. ↑Body temperature = ↑HR. R-atrial distension, by ↑blood volume = ↑HR – R-atrial distension →Stretch receptors → medullary CV-center → sympathetic stimulation → ↑HR Catecholamine: AD, NAD = ↑HR (+ve chronotropic effect). 88 The End 89