The conducting system of the heart

The conducting system of the heart 1. The nodal system: Which consists of two nodes in the right atrium: The sinoatrial node (also called the S-A node or the sinus node). The atrioventricular node (also called the A-V node). 2. The internodal pathway: 3. The purkinje system (also called the His-Purkinje system): The atrioventricular bundle (also called the A-V bundle or the bundle of His). The right and left bundle branches. The Purkinje fibers.

Functional histology 1. The contractile muscle fibers: Differences between the contractile cardiac muscle fibers and skeletal muscle fibers. 2. Nodal fibers of the S-A and A-V nodes: 3.The Purkinje fibers of the Purkinje system:

INTERCALATED DISC (TIGHT JUNCTION)

STRUCTURE OF A MYOCARDIAL CELL Mitochondria Sarcolemma T-tubule SR Fibrils

Myocardial Contraction Myocardial fiber Myofibril myosin Myofilaments actin relaxed The heart muscles are composed of myocardial fibers which comprises smaller myofibrils. Myofibrils are made up of yet smaller myofilaments, each is 5 – 10 nanometers. The thin filaments (actin) and the thick filaments (myosin) are linked together by cross bridges, which project from myosin. Myocardial contraction occurs when cross bridges from myosin link to appropriate sites on the actin filaments and swivel to a new position. This sliding process is initiated and controlled by Ca++ ions. The energy required for this motion is supplied by ATP (see next slide). For further details, please consult any textbook on physiology (e.g., Best and Taylor’s Physiological Basis of Medical Practice) or cardiovascular dynamics (e.g., Rushmer). contracted

Functions of the atria      1. The main function of the atria is to accommodate blood returning to the heart during ventricular systole until it is passed on to the ventricles during ventricular diastole.      2. The pumping action of the atria increases the ventricular filling. This increases the pumping capacity of the ventricles by 15-20%.

Function of the ventricles      The ventricles are the central pumps of the circulatory system. They pump the venous return which they received by the atria. The right ventricle pumps the systemic venous return into the pulmonary circulation and the left ventricle pumps the pulmonary venous return back into the systemic circulation.

Ventricular volumes End-diastolic volume (EDV): is the volume of blood in the ventricle at the end of diastole. It is about 130 ml.       End-systolic volume (ESV): is the volume of blood in the ventricle at the end of systole. It is about 55 ml. Stroke volume (SV): is the volume of blood that is pumped by the ventricle per beat. It is equal to the difference between the EDV and ESV. Its is about 75 ml. Diastolic filling volume (DFV): is the volume of blood which flows from the atrium into a ventricle during diastole. It is equal to the difference between the EDV and the ESV. It is about 75 ml.

Properties of the cardiac muscle The heart has four basic properties which are essential for its functioning as the central pump of the CVS. These are:         1. Autorhythmicity       2. Conductivity      3. Excitability       4. Contractility

Autorhythmicity Automaticity Rhythmicity Autorhythmicity Autorhythmicity is a myogenic innate property of the heart independent of its nerve supply.

Autorhythmicity The conducting system of the heart is responsible for generating rhythmic, electrical impulses which drive the heart to beat in a rhythmic way. The focus which generates the highest frequency of impulses is he one that drives the whole heart and is called the pacemaker of the heart. The normal pacemaker of the human heart is the S-A node.

Autorhythmicity There are several possible sites in the conducting system that can act as possible pacemakers: Sino-atrial (SA) node Atrio-ventricular (AV) node Purkinje system   If the primary pacemaker is damaged or blocked, the secondary pacemaker takes over. If the flow of impulses from the atria to the ventricles stops completely, the tertiary pacemaker takes over and the ventricles continue to beat at the idioventricular rhythm.

CARDIAC ELECTROPHYSIOLOGY

THE RESTING MEMBRANE POTENTIAL OF THE CARDIAC CELL OUT K+ K+ 5mEq 145mEq Na+ Na+ 145mEq 10mEq Em= -60LogKi/Ko -90mv

The pacemaker potential The pacemaker cells are characterized by having an unstable membrane potential. This is the basis for automaticity

Na+ K+ AUTOMATICITY Gradually increasing PNa -0 -60 mV THRESHOLD RESTING

The pacemaker potential The pacemaker cells are characterized by having an unstable membrane potential. After firing an action potential, the membrane potential decreases i.e. the membrane depolarizes gradually from a basal value of ~ -60mV to a critical firing level of –45 mV. At this level, an action potential is fired and the cycle is repeated. The gradual depolarization of the S-A nodal cells is called the pacemaker potential or the prepotential. The early part of the pacemaker potential is caused by a decrease in the permeability of the membrane to K+. The late part is caused by Ca++ influx through the transient (T-type) Ca++-channels.

THE SA NODE PACEMAKER POTENTIAL

The pacemaker action potential When the pacemaker potential reaches the critical level (~ -45 mV), an action potential is produced in the pacemaker cells. This action potential propagates to the surrounding myocardial cells.

THE SA NODE ACTION POTENTIAL

ELECTROPHYSIOLOGY OF THE CONTRACTILE FIBER AMP +20 1 To oscilloscope 2 3 mv Cardiac Cell 4 -90 300 t (msec)

MEMBRANE POTENTIAL (mV) PHASE 0 = Rapid Depolarization (inward Na+ current) 1 1 2 2 = Plateau (inward Ca++ current) 3 = Repolarization (outward K+ current) MEMBRANE POTENTIAL (mV) 4 = Resting Potential 3 4 -90 TIME

ACTION POTENTIALS FROM DIFFERENT AREAS OF THE HEART ATRIUM VENTRICLE mv -90mv mv -90mv mv -60mv SA NODE time

ACTION POTENTIALS VENTRICULULAR CELL SAN 1 2 3 3 4 -50 -50 MEMBRANE POTENTIAL (mV) 4 -100 -100

The pacemaker action potential differs from the action potential of the contractile myocardial cells in the following:       Depolarization phase is mainly due to Ca2+ influx through long-lasting (L-type) Ca2+-channels. Depolarization phase is relatively slow to develop. There is no plateau phase. Repolarization immediately follows depolarization.

Ectopic foci An ectopic focus is an area in the contractile myocardium, which discharges electrical impulses. Normally, the contractile myocardium has a stable resting membrane potential and is incapable of discharging impulses. Under some non-physiological conditions, some myocardial cells acquire rhythmic electrical activity and act as foci that send un-timed electrical impulses or might even take over the heart and act as the pacemaker.

Chronotropism means an influence on the heart rate. A +ve chronotropic factor (or effect) is one that increases the heart rate. A –ve chronotropic factor (or effect) is one that decreases the heart rate.

Factors that influence cardiac autorhythmicity Several factors influence autorhythmicity by influencing the rate of discharge from the heart pacemaker. These factors could be classified into:       Nervous factors      Chemical factors Physical factors Mechanical factors

Factors that influence cardiac autorhythmicity

Nervous factors The most important factor in the regulation of the heart rate is the activity of the cardiovascular centers in the medulla oblongata. This activity is transmitted to the heart via its sympathetic and parasympathetic nerve supply.

Sympathetic nerve supply There is a resting sympathetic tone that tends to increase the heart rate up to 120 beats/min. This tone is weak and is masked by the strong inhibitory vagal tone that decreases the heart rate down to 75 beats/min during rest. However, stimulation of the sympathetic cardiac nerves has a +ve chronotropic effect. The heart rate may g up to 200 beats/min. The sympathetic chemical transmitter noradrenaline decreases the permeability of the pacemaker membrane to K+. This accelerates the depolarization of the membrane → shortens the duration of the pacemaker potential → increases the frequency of discharge of impulses from the S-A node → increases the heart rate.

Parasympathetic nerve supply There is a resting inhibitory vagal tone that keeps the heart rate at its resting level of ~ 75 beats/min. During deep quite sleep, the vagal tone increase and the heart rate decreases down to 60 beats/min. Vagal stimulation has a –ve chronotropic effect. The parasympathetic chemical transmitter acetyl choline increases the permeability of the pacemaker membrane to K+. This slows down the depolarization of the membrane → prolongss the duration of the pacemaker potential → deccreases the frequency of discharge of impulses from the S-A node → decreases the heart rate.

Factors that influence cardiac autorhythmicity

Cutting or blocking the vagal nerve supply to the heart (e. g Cutting or blocking the vagal nerve supply to the heart (e.g., by atropine) leads to an increase in the heart rate up to ~ 120 beats/minute. This is the sinus rhythm boosted by the resting sympathetic tone. If this is followed by cutting or blocking the sympathetic nerve supply to the heart (e.g., by atenolol), the heart rate decreases down to 105 beats/minute; the natural inherent sinus rhythm. Cutting or blocking the sympathetic nerve supply to the heart with an intact vagal parasympathetic supply produces no significant change in heart rate, i.e. it remains at its resting level of ~ 75 beats/minute.

Both substances have a +ve chronotropic effect. Chemical factors Adrenaline and noradrenaline are released into the blood under conditions of stress. Both substances have a +ve chronotropic effect.

Physical factors Arise in body temperature by 1 °C increases the heat rate by 20 beats/minute. The rise in body temperature increase the heart rate by increasing the permeability of he membrane to Ca++ during the pacemaker potential and increasing the speed of ionic fluxes across the membrane during the action potential. The only physiological condition that rises body temperature above the normal resting range is muscular exercise.

Mechanical factors

The sick sinus syndrome This is a pathological condition where there is bradycardia accompanied by frequent attacks of dizziness and syncope. It is caused by a disease of the S-A node depressing its activity and decreasing the rate of impulse generation. This condition is treated by implantation of an artificial pacemaker.

Impulses can spread easily between cardiac muscle fibers. Conductivity Impulses can spread easily between cardiac muscle fibers. Yet, conduction in the heart is normally carried out by the specialized conducting system to ensure the spread of the excitation wave from the S-A node to all over the heart in certain pattern.

The origin and pathway of the cardiac impulse The normal cardiac impulse originates inside the S-A node, the normal pacemaker of the heart. The impulse is then conducted to the surrounding atrial wall through the peripheral S-A nodal tissue. Then it propagates in three pathways:   To the right atrium through the atrial muscle fibers To the left atrium through the interatrial ‘Bachmann’s bundle’ To the A-V node through the internodal bundles

The A-V bundle conducts the impulses to the buddle branches. The impulse picked up by the A-V node is delayed for 0.1 – 0.15 second, then passed on to the A-V bundle. The A-V bundle conducts the impulses to the buddle branches. Then from the bundle branches to the Purkinje fibers on to the ventricular muscle fibers.

Important functional characteristics of the A-V node The A-V node is characterized by: Very slow conductivity: This delays the transmission of impulses to the ventricles (A-V nodal delay). This delay allows the atria to finish with their systole before passing the impulse to the ventricles to start ventricular systole. Long absolute refractory period after conducting an impulse: This limits the number of impulses that can be transmitted from the atria to the ventricles to 230 impulse/min. This protects the ventricles from receiving high frequency of impulses from the atria.

Factors that influence conductivity       Sympathetic stimulation accelerates conduction and decreases the A-V nodal delay. Parasympathetic stimulation slows conduction and may produce various degrees of heart block.

The one-way conduction in the A-V bundle The A-V bundle conducts impulses only in one direction, i.e. from the A-V node to the bundle branches. This prevents the reentry of impulses from the ventricles into the atria.

Excitability is the ability to respond to stimuli.   The resting membrane potential of the contractile fibers is stable at about – 90 mV. When an effective stimulus is applied, a propagated action potential is produced in the cell membrane.

Phases and ionic basis of the myocardial action potential

MEMBRANE POTENTIAL (mV) PHASE 0 = Rapid Depolarization (inward Na+ current) 1 1 2 2 = Plateau (inward Ca++ current) 3 = Repolarization (outward K+ current) MEMBRANE POTENTIAL (mV) 4 = Resting Potential 3 4 -90 TIME

Phase 0 (Rapid depolarization): It is caused by the rapid influx of Na+ into the cell.       Phase 1 (Early partial repolarization): During this phase, the permeability of the membrane to Na+ is rapidly reduced, but the membrane permeability for both Ca2+ and K+ increases. The overall effect is a small change in the membrane potential toward the resting membrane potential (repolarization). Phase 2 (Plateau of the action potential): This coincides with an increased permeability for Ca2+. The inward movement of Ca2+ and the decreased efflux of K+ maintain the membrane potential near zero during this phase of the action potential. Phase 3 (Rapid repolarization): due to a reduction of the inward Na+ and Ca2+ currents and a large increase in the outward K+ current. Phase 4 (Complete repolarization): the membrane goes back to the resting level (- 90 mV). Na+-K+ pump works to drive the excess Na+ out and the excess K+ in.

Excitability changes following an effective stimulus to contractile cardiac muscle Following the application of an effective stimulus to ventricular cardiac muscle, its excitability passes by the following phases:

REFRACTORY PERIODS MV ARP -90 RRP TIME

The absolute refractory period During the absolute refractory period, the excitability level is 0%. No stimulus however strong can produce a propagated action potential in the heart. This period begins with sarcolemmal depolarization till mid-repolarization ( to a membrane potential of –40 to –50 mV). It lasts for the whole period of systole and the early part of diastole.

The relative refractory period During the relative refractory period the excitability level is more than 0 but less than 100% of the resting basal level. The heart responds only to stronger stimuli. It is a short period that begins at mid-repolarization and ends shortly before complete repolarization. It lasts for a short period during diastole.

The significance of the long absolute refractory period of the ventricular muscle It lasts for the whole period of systole and the early part of diastole. This means that the ventricle would not respond to any stimulus until it finishes with its systole and have some diastole. So the long absolute refractory period protects the ventricle against tetnization if it receives multiple successive stimuli.

Contractility Contractility is the ability of the muscle to convert the potential energy of food into mechanical energy.

Calcium transport across the myocardial sarcolemma There are four different ways for transport of calcium across the myocardial sarcolemma: Transient (T-type) calcium channels Long-lasting (L-type) calcium channels Calcium pump Na+-Ca2+ exchanger

Ca++ SARCOLEMMA Mitochondria 20% T-tubule 80% SR THICK MYOFILAMENT 10% Mitochondria 20% 80% T-tubule Ca++ SR THICK MYOFILAMENT THIN MYOFILAMENT

Excitation-contraction coupling in the myocardial cell Contraction: When the myocardial cell is excited → Na+ influx → depolarization of the sarcolemma → depolarization of the T-tubules → Ca2+ influx through slow calcium channels, this calcium is called depolarizing calcium → release of calcium from the sarcoplasmic reticulum, this calcium is called activator calcium. → activator calcium starts contractile process by binding to troponin-C.

Excitation Contraction Coupling Excitation contraction coupling is similar in cardiac and skeletal muscle. Increased intracellular Ca2+ triggers contraction by binding to troponin on the thin filament. In cardiac muscle Ca2+ comes from both the extracellular fluid and sarcoplasmic reticulum.

Relaxation Relaxation: Calcium is cleared from the sarcoplasm by the Na+-Ca2+ exchanger and two calcium pumps, one in the sarcoplasmis reticulum that reuptakes calcium back into the reticulum, and another in the sarcolemma that pumps calcium out into the extracellular fluid. The clearance of calcium from the sarcoplasm terminates the contraction and starts the relaxation process.

The preload and afterload of the heart During diastole, blood fills the ventricle till it reaches the end-diastolic volume (EDV) before the start of contraction. Therefore, the EDV is called the preload of the heart. The ventricle then contracts to eject the blood against the resistance of the arterial blood pressure. Therefore, the load of the arterial blood pressure is called the afterload of the heart.

Inotropism means an influence on contractility. A +ve inotropic factor or effect is one that increases myocardial contractility. A -ve inotropic factor or effect is one that decreases myocardial contractility.

Factors that influence myocardial contractility * Sympathetic stimulation has a +ve inotropic effect * Parasympathetic stimulation has a –ve inotropic effect on the atrial myocardium only because the vagus nerves do not supply the ventricles * The preload (EDV): * Heart rate: