PHYSIOLOGICAL PROPERTIES OF HEART. HEART AS A PUMP
1. Morphology and functional organization of heart
a) Structure of heart. The heart contains four chambers: two upper atria, which receive venous blood and two lower ventricles, which eject blood into arteries. The right ventricle pumps blood to the lungs, where the blood becomes oxygenated. The left ventricle pumps oxygenated blood to the entire body.
The right and left atria receive blood from the venous system. The right atrium and ventricle are separated from the left one by septum, which is the muscular wall. This septum normally prevents mixture oxygenated and not oxygenated blood.
Between the atria and ventricles there is a layer of dense connective tissue known as fibrous skeleton of the heart. The connective tissue of skeleton also forms rings, called annuli fibroses around two pairs of one-way valves.
b) Structure of myocardium. Bundles of myocardial cells in the atria attach to the upper margin of this fibrous skeleton and form a myocardium. The myocardial cell bundles of the ventricles attach to the lower margin and form a different myocardium. As a result, the myocardium of the atria and ventricles are structurally and functionally separated from each other.
Weight of whole myocardium consist 250-300g. Atria myocardium has two layers of muscle cells – circular and
longitudinal. Circular cells layers surround mouth of vessels, which fall into atria and may cover again it in constriction.
Ventricles myocardium has three layers of muscle cells. External and internal layer have spiral form and are common for both ventricles. Middle layer has circular orientation and is separated in every ventricle.
c) Functional specialties of myocardial cells. Myocardial cells contain actin and myosin filaments and contracts by means of the sliding filament mechanism. Myocardial cells are joined by gap junctions, due to which electrical impulses can spread to all cells in the mass. Sarcoplasmatic reticulum in myocardial cells is developed slightly. That is why some amount of calcium may enter the myocardial cell from the outside.
Besides contractive myocardial cells there are modified cells of the conduction system of the heart. They can generate and conduct impulses through myocardium.
d) Electrophysiological properties of the contractive myocardium. The main electrophysiological properties of the contractive myocardium are automaticity, contractility, conductability and excitability.
Automaticity is property to contract replying to electrical impulses, originated in pacemaker cells of the conduction system of the heart.
Contractility is property to contract replying to irritation.
Conductibility is property to spread electrical impulses through the conduction system and contractive myocardium.
Excitability is property to reply the irritation.
2. Automaticity of the heart
a) Structure of conduction system.
Specialized excitatory and conductive system of the heart: consists of:
1. Sinus node “SA” node: also called sinoatrial node, located in the right atrium. It is concerned with the generation of rhythmical impulse; it is the pacemaker of the heart that initiates each heart beat. This automatic nature of the heart beat is referred to as automaticity.
2. Internodal pathways conduct the impulse generated in SA node to the AV node.
3. The AV node (atrioventricular node), located near the right AV valve at the lower end of the interatrial septum, in the posterior septal wall of the right atrium. At which impulse from the atria is delayed before passing into the ventricles.
4. The AV bundle (bundle of His) conducts the impulse from the atria into ventricles.
5. The left and right bundles of purkinje fibers, which conduct the cardiac impulse to all parts of the ventricles. The purkinje fibers distribute the electrical excitation to the myocytes of the ventricles.
The SA node as the pacemaker of the heart: (Automaticity & rhythmicity)
Automaticity is the property of self-excitation (i.e. the ability of spontaneously generating action potentials independent of any extrinsic stimuli) while rhythmicity is the regular generation of these action potentials. In other words, the cardiac impulse normally arises in the SA node, which has the capability of originating action potentials and functioning as pacemaker. This action potential then spreads from the SA node throughout the atria and then into and throughout the ventricles.
The contractile cardiac muscle cells don’t normally generate action potentials but they can do in certain pathological conditions. This mean that all parts of the conduction system are able to generate a cardiac impulse; (autorhythmicity), but the normal primary pacemaker is the SA node, while the AV node is a secondary pacemaker and the Purkinje system is a tertiary (or latent) pacemaker. The AV node acts only if the SA node is damaged or blocked, while the tertiary pacemaker takes over only if impulse conduction via the AV node is completely blocked.
The SA node discharges at an intrinsic rhythmical rate of 100-110 times per minute (sinus rhythm). Under abnormal condition; the AV nodal fibers can exhibit rhythmical discharge and contraction at a rate of 40 to 60 times/minute. While those of purkinje fibers discharge at a rate between 15 and 40 times/minute.
Autorhythmicity is a myogenic property independent of cardiac innervation. This is evidenced by the following:
* Completely denervated heart continues beating rhythmically.
* Hearts removed from the body and placed in suitable solutions continue
beating for relatively long periods.
* The transplanted heart (denervated heart) has no nerve supply but they beat regularly.
Self-excitation of SA node:
What causes the SA node to fire spontaneously?
Although the SA node discharges at an intrinsic rhythmical rate of 100-110 times per minute but the pulse rate averages 70 or 80 times per minute, this is because of the effect of vagal tone. SA node does not have a stable resting membrane potential which starts at about – 60 mV. This is due to the inherent leakiness of the SA nodal fibers to Na+ ions that causes this self-excitation (Na+ influx). in other words, because of the high Na+ ions concentration in the ECF as well as the negative electrical charge inside the resting sinus nodal fibers, the positive Na+ ions outside the fibers tend to leak to the inside, rising the membrane potential up to a threshed to fire an action potential.
Atrioventricular node (AV node):
The conductive system is organized, so that cardiac impulse will not travel from the atria into ventricles too rapidly. There is a delay of transmission of the cardiac impulse in the AV node to allow time for the atria to empty their blood into the ventricles before ventricular contraction begins.
b) Electrophisiological properties of conduction system.
Action potential of SA node
The resting membrane potential of SA node is of -55 to -60 mV (millivolts). The cause of this reduced negativity “less negative” is that the cell membrane of the sinus fibers are naturally leaky to sodium ions “Na+ influx”. Therefore; Na+ influx causes a rising membrane potential “gradual depolarization” which when reaches a threshold voltage at about – 40 mV, the fast calcium and sodium channels opened, leading to a rapid entry of both Ca+2 and Na+ ions causing the action potential to about 0 mV (zero), to be followed by repolarization which is induced by K+ efflux out of the fiber because of the opening of K+ channels. This repolarization carries the resting membrane potential down to about -55 to -60 mV at the termination of action potential.
Action potential of ventricular cardiac muscle fiber
The membrane potential of cardiac ventricular muscle fiber cells is about -90 mV; the interior of the cell is electrically negative with respect to the exterior due to disposition; distribution of ions mainly Na+, K+ and Ca+2 ions across its membrane.
The action potential (AP) is an electrical signal or impulse produced by ionic redistribution that the potential changes into positive inside the cell (depolarization), to be followed by restoration of the ions; returning back to the resting potential (repolarization). Stimulation of cardiac muscle cells by SA produces a propagated action potential, that is responsible for muscle contraction i.e., excitation-contraction coupling. In other words, stimulation of cardiac muscle cells specifically those of the ventricles is performed by the propagated AP of the SA node from which the electrical impulses originating and propagated over the heart. According to the figure (a), the propagated AP of the SA node depolarized the ventricular muscle fiber cells rapidly with an overshoot (phase 0), followed by a plateau at around zero potential level (phase 2). This plateau is unique for the heart muscle; and is followed by phase 3 and 4; as final repolarization i.e., for the potential to return to baseline.
Ionic basis of the action potential of the cardiac ventricular muscle fiber cell:
The action potential of cardiac ventricular muscle fiber cell includes the following phases (a):
* Phase 0 (upstroke): initial rapid depolarization with an overshoot to about +20 mV are due to opening of the voltage-gated Na+ channels with rapid Na+ influx.
* Phase 1 (partial repolarization): initial rapid repolarization is due to K+ efflux (K+ outflow) followed the closure of Na+ channels when the voltage reaches at nearly +20 mV.
* Phase 2 (plateau): subsequent prolonged plateau is due to slower and prolonged opening of the voltage-gated Ca+2 channels with Ca+2 influx, Ca+2 enter through these channels prolong depolarization of the membrane.
* Phase 3 (rapid repolarization): final repolarization is due to opening of the voltage-gated K+ channels at zero voltage with rapid K+ outflow (K+ efflux) followed the closure of Ca+2 channels and, this restores the membrane to its resting potential.
* Phase 4 (complete repolarization): The membrane potential goes back to the resting level (-90 mV) i.e., restoration of the resting potential. This is achieved by the Na+-K+ pump that works to move the excess K+ in and the excess Na+ out.
c) Function of pacemaker centers.
Some other regions of the heart, including the area around SA-node and the atrio-ventricular bundle can potentially produce pacemaker potentials. The rate of spontaneous depolarization of these cells however is slower, than that of SA-node.
As it determined SA-node produce 60-90 impulses per minute, AV-node – 40-50, bundle of His – 20-30 and Purkinje fibers 10-20 impulses per minute. The potential pacemaker cells are stimulated by action potential from SA-node before they can stimulate themselves through their own pacemaker potentials. If action potentials from the SA-node are prevented from reaching these areas (through blockade of conduction), they will generate pacemaker potentials at their own rate and save as sites for the origin of action as pacemakers.
A pacemaker other than SA-node is called as ectopic pacemaker or ectopic focus.
If the heart of a frog is removed from the body, and put in physiological solution, it will still continue to beat as long as the myocardial cells remained alive.
At a result of experiments with isolated myocardial cells and clinical experience with patients who have specific heart disorders, many regions within the heart have been shown to be capable of originating action potentials and functioning as pacemakers.
In a normal heart, however, only one region demonstrates spontaneous electrical activity and by this means functions as a pacemaker – SA-node.
Conductibility of the heart
a) Conduction of impulses in atria. After excitation of SA-node impulses conduct by bundle of Thorel, Venkenbuh and Buhman to AV-node.
Action potentials from SA-node spread at a rate of 0,8-1,0 m/s across the myocardial cells of both atria. At first the right atrium is excited and left is the second.
b) Peculiarities of conduction through AV-node. The conduction rate slows considerably as the impulse passes into the AV-node. Slow conduction of impulses (0,03-0,05 m/s) through the AV-node is caused by special form of AV-node and peculiarities of impulse development in cells of AV-node, as absence of rapid diffusion of ions. Slow conduction in AV-node is necessary for proper order of contracting atria and ventricles.
c) Excitation of ventricles. After the impulses spread through the AV-node, the conduction rate increases in the atrio-ventricular bundle and reaches 5 m/s in the Purkinje fibers. As a result of this rapid conduction of impulses, ventricular contraction begins 0,1-0,2 s after the contraction of atria.
High velocity of impulses in ventricles is caused by rapid Na+-gates.
At first middle part of septum is excited, than impulses spread to apex of heart, than to the right ventricle wall, to the left ventricle wall and to basal parts of ventricles myocardium.
Excitability of heart
a) Excitability changing during excitation. Once contractive myocardial cell has been stimulated by action potentials origin in SA-node, it produces its own action potentials. The majority of myocardial cells have resting membrane potentials of about -90 mV. When stimulated by action potentials from a pacemaker region these cells become depolarized to threshold. At this point their voltage – regulated Na+-gates open.
The upshot phase of the action potential of no pacemaker cells is due to the inward diffusion of Na+. This period called depolarization.
Following the rapid reversal of the membrane polarity, the membrane potential quickly declines to about -15 mV. Opening K+ and Cl- gates and inward diffusion of K+ and Cl- causes it. This period called quickly initial repolarization.
Then this level potential maintained for 200-300 ms and cells plato phase. It’s due to opening of slow Ca2+ gates. Gradually slow Ca2+ diffusion stops and than diffusion of K+ increases. Rapid repolarization at the end of the plato is achieved by rapid outward diffusion of K+. During last phase of rest initial distribution of ions inwards and outwards is recovered by function of the sodium-potassium pumps. The heart normally cannot be stimulated until after it has relaxed from its previous contraction because myocardial cells have long refractory periods. It corresponds to the long duration of their action potentials. Summation of contractions is thus prevented and myocardium must relax after each contraction. The rhythmic pumping action of the heart is thus ensured.
Refractory period:
* Absolute refractory period (ARP), it is the interval during which no action potential can be produced, regardless of the stimulus intensity i.e., no stimulus however strong, can produce a propagated action potential. It lasts the upstroke plus plateau and initial repolarization till mid-repolarization at about -50 to -60 mV. It means that the cardiac muscle caot be exited during the whole period of systole and early part of diastole. This period prevents waves summation and tetanus.
* Relative refractory period (RRP), it is the interval during which a second action potential can be produced but at higher stimulus intensity i.e., the heart responds only to stronger stimuli. It lasts from the end of ARP (midrepolarization) and ends shortly before complete repolarization i.e., it lasts for a short period during diastole.
b) Excitability of the heart and skeletal muscles. Electrical impulses that originate at any point of myocardium can spread to all cells, according to ruler “all or nothing”. Because all cells in myocardium are electrically joined a myocardium behaves as a single functional unit. Unlike it, in skeletal muscle contraction depends oumber of excited neurons, which stimulate motor unit. Unlike skeletal muscles, cardiac muscle capable to produce action potentials by pacemaker cells. The rate of heartbeat is regulated by autonomic nervous system. In difference, skeletal muscles are regulated by somatic nervous system.
5. Contractibility of the heart
a) Mechanism of contraction and relaxing of the heart muscle. Like skeletal muscle cells, cardiac muscle cells are striated. They contain actin and myosin filaments arranged in the form of sarcomeres. They contract by means of the sliding filament mechanism. Myocardial cells are short, branched and interconnected. Gap junctions join adjacent myocardial cells. That is why a myocardium contracts to its full extent each time and all of its cells contribute to the contraction. After opening Ca2+- gates contraction begins. The mechanism of contraction is similar to skeletal muscles. Sliding on thin filaments they produce shortening of the sarcomeres. In the process of contraction, the thin filaments slide deeper and deeper toward the center, producing increasing amounts of overlap with thick filaments. Sliding of the filaments is produced by the action of numerous cross brigs that extend out from the myosin toward the action. Before the cross brigs combine with actin the globular head function as myosin ATP-ase enzymes. Then cross brigs combine with actin and can attach to actin.
Mechanism of contraction and relaxing of the heart muscle.
b) Contractibility cardiac and skeletal muscles:
– In skeletal muscles long fibrose cells are separated from each other functionally and structurally. But myocardial cells are short, branched and interconnected by gap junctions.
– Skeletal muscle produce contractions, which are graded depending on the number of cells stimulated. But a myocardium contracts as a single functional unit.
– Skeletal muscles require external stimulation by somatic motor nerves before they can produce action potentials and contract. But cardiac muscle is able to produce action potentials automaticity.
– Skeletal muscle capable to summation of contraction, but myocardial muscle pumps the blood by rhythmic contractions.
Contractility is the ability of the cardiac muscle to contract.
The effect of various factors on contractility is called inotropism; a positive (+ve) inotropic effect means an increase in myocardial contractility, whereas a negative(-ve) inotropic effect means a decrease in myocardial contractility.
Excitation-Contraction coupling in the heart muscle:
As in skeletal muscles, the depolarization wave reaching via the T tubules causes the opening of Ca+2 channels in the sarcoplasmic reticulum adjacent to the T-tubules. The released Ca+2 from the cisternae of the sarcoplasmic reticulum (activator Ca+2; aCa+2) binds to troponin C, leading to cross bridge formation between actin and myosin, which results in contraction.
In cardiac muscle, the amount of this activator Ca+2 is often insufficient to initiate contraction, but it can be increased indirectly by the following mechanism:
The depolarization wave in the T-tubules opens the long-lasting Ca+2 channels in the T-tubule membrane, and sarcolemma, Ca+2 diffuses from the ECF through these channels into the cardiac muscle fibre cell causing a small increase in the cytosolic (fluid of the cytoplasm) calcium concentration in the region of the T-tubules and adjacent sarcoplasmic reticulum. This Ca+2 is called depolarizing Ca+2, and although its amount is normally very small, yet it is important because it acts as a signal for the release of large amount of activator Ca+2 from the cisternae of sarcoplasmic reticulum, it is mainly this cytosolic Ca+2 that causes the contraction, i.e. once Ca+2 is in the cytoplasm, it binds to troponin and stimulates contraction. As a result, myocardial cells contract when they are depolarized. The force of contraction is directly proportional to the amount of cytosolic Ca+2.
Contraction ends when the cytosolic Ca+2 concentration restored to its original level. In other words, relaxation of the cardiac muscle occurs as a result of release of the actin-myosin combination, this is achieved by decreasing the intracellular Ca+2 to its pre- contraction level, which occurs by:
1- Active re uptake of Ca+2 into the sarcoplasmic reticulum by Ca+2 pump (primary active transport of Ca+2).
2- Active pumping of excess Ca+2 outside the fibres by Na+- Ca+2 exchanger carrier protein (secondary active transport ; counter transport).
The heart normally cannot be stimulated again until after it has relaxed from its previous contraction because myocardial cells have long refractory periods that correspond the long duration of their action potentials. Summation of contractions and tetanus are thus prevented, and the myocardium must relax at each contraction to ensure the rhythmic pumping action of the heart.
Factors that affect cardiac contractility:
* Mechanical
* Cardiac
* Extra cardiac
Mechanical factors:
* Preload (venous return)
* Afterload
The preload:
The preload is the load that determines the initial length of the resting muscle before contraction. The level of the preload is represented by the end-diastolic volume (EDV) i.e., by the venous return (VR). It affects the tension developed in the muscle. When the venous return (EDV), increases, the strength of ventricular contraction increases too, leading to an increase in the stroke volume (Frank-Starling law).
Frank-Starling’s law of the heart
This law describes the length-tension relationship in muscles; it states that the force of contraction of the ventricles depends on the initial length of ventricular muscle fibers. In such a way, that the force of myocardial contraction is directly proportional to the initial length of the cardiac muscle fibres (i.e. to the preload (VR) or EDV). This means that the greater the degree of stretching of the myocardium before contraction, the greater the force of contraction. In other words, Frank-Starling law reflects the relationship between ventricular end-diastolic volume (EDV) and stroke volume; when the blood returns to the heart during the filling phase, this blood will distend the ventricles so the ventricles will produce more powerful contraction to pump the increased volume of the blood.
The Significance of Frank-Starling’s law
The Starling’s law allows autoregulation of myocardial contractility (regulation of the contractility by changing the length of the muscle fibers), in the following conditions:
(1) Iormal hearts. Starling’s law allows changes in the right ventricular output to match changes in the venous return (VR), and maintains equal outputs from both ventricles. For example, if the systemic VR increases, the EDV of the right ventricle increases, leading to a forceful contraction that increases its output to match the increased VR. At the same time, the increased right ventricular output increases the pulmonary VR to the left ventricle, which also increases its EDV, resulting in an increase of its output, which balances the increased right ventricular output.
(2) In denervated hearts (e.g. transplanted hearts); autoregulation of myocardial contractility becomes the main mechanism.
(3) In cases of rise of the arterial blood pressure: the stroke volume of the left ventricle would decrease. However, the retained blood in the left ventricle plus blood returning to it from the left atrium during the next diastole increase the EDV. This leads to a forceful contraction, thus the accumulated blood in the left ventricle will be ejected in spite of the increased arterial blood pressure.
The Afterload:
The afterload is the load that the muscle faces when it begins to contract. In the intact heart, the afterload is produced by the aortic impedance which is determined by:
* The aortic pressure (arterial systolic blood pressure).
* The arterial wall rigidity (arteriosclerosis).
* Blood viscosity (polycythemia).
Cardiac factors:
* The myocardial mass.
* The heart rate.
The myocardial mass:
A significant injury or loss of the functioning ventricular muscle (e.g. due to ischemia or necrosis) decreases the force of myocardial contractility. This also occurs in cases of heart failure.
The heart rate:
The force of cardiac contractility is affected by the frequency of stimulation. An increase in the frequency of stimulation (i.e. shortening the intervals between the stimuli) causes a proportional increase in the force of contraction.
Accordingly, tachycardia causes a +ve inotropic effect while bradycardia exerts a -ve inotropic action. The +ve inotropic effect in tachycardia is due to the increase in the number of depolarization (which increases the intracellular Ca+2 content and its availability to the contractile proteins (troponin C)).
Extra cardiac factors:
These factors affect the cardiac inotropic state and they include the following:
* Neural
* Physical
* Chemical
Neural factors:
Sympathetic stimulation and noradrenaline exert a +ve inotropic effect by increasing;
* Cyclic-AMP in the cardiac muscle fibres (which leads to activation of the Ca+2 channels and more Ca+2 influx from the ECF).
* The heart rate.
Conversely, parasympathetic stimulation and acetylcholine exert a -ve inotropic effect (by opposite mechanism) but on the atrial muscle only (since the vagi nerves don’t supply the ventricles).
Physical factors:
A moderate rise of the body temperature strengthens cardiac contractility (by increasing the Ca+2 influx and ATP formation in the muscle) while an excessive rise of the body temperature (e.g. in fever) exhausts the metabolic substrates in the cardiac muscle and decreases its contractility. Hypothermia also decreases cardiac contractility.
Chemical factors:
(A) Hormones:
Catecholamines (epinephrine, norepinephrine and dopamine), glucagon and the thyroid hormones; all exert a +ve inotropic effect.
(B) Blood gases:
Moderate hypoxia (O2 lack) and hypercapnia (CO2 excess) increase the cardiac contractility, whereas severe hypoxia and hypercapnia directly depress the cardiac muscle and decrease its contractility.
(C) H + ion concentration (pH):
An increase of the blood [H+] i.e. drop of the blood pH (acidosis) produces a -ve inotropic effect, whereas a decrease of the blood [H+] i.e. rise of the blood pH (alkalosis) produces a + ve inotropic effect.
(D) Inorganic ions:
* Sodium: Hypernatraemia favors Na+ influx and Ca+2 efflux by the
Na+-Ca+2 exchanger carrier, thus it has a -ve inotropic effect. On the other
hand, hyponatraemia exerts a +ve inotropic effect by an opposite mechanism.
* Potassium: Hyperkalaemia has a -ve inotropic effect (weakens the myocardial contractility; flaccidity) and may stop the heart in diastole. This is because the excess K+ in the ECF decreases the resting membrane potential (more positive resting membrane potential; closer to the threshold)) in the cardiac muscle fibers, so the amplitude of the action potential is reduced leading to less influx of the depolarizing Ca+2 and in turn less release of activator Ca+2 from the sarcoplasmic reticulum. In addition, Hyperkalaemia increases excitation and decreases conduction leading to ectopics and dilated, flaccid heart. On the other hand, hypokalaemia produces a +ve inotropic effect by an opposite mechanism.
* Calcium: Hypercalcaemia exerts a +ve inotropic effect as a result of more cytosolic Ca+2. Whereas hypocalcaemia has a little (or no) -ve inotropic effect, since lowering of the serum Ca+2 level causes fatal tetany before affecting the heart. However, hypocalcaemia causes cardiac flaccidity like Hyperkalaemia.
Functions of the Heart
* Generating blood pressure
* Routing blood
* Heart separates pulmonary and systemic circulations
* Ensuring one-way blood flow
* Regulating blood supply
* Changes in contraction rate and force match blood delivery to changing metabolic needs
Electrical Activity of Heart
* Heart beats rhythmically as result of action potentials it generates by itself (autorhythmicity)
* Two specialized types of cardiac muscle cells
* Contractile cells
* 99% of cardiac muscle cells
* Do mechanical work of pumping
* Normally do not initiate own action potentials
* Autorhythmic cells
* Do not contract
* Specialized for initiating and conducting action potentials responsible for contraction of working cells
Intrinsic Cardiac Conduction System
* SA Node 70-80 bpm
* Sets the pace of the heartbeat
* AV Node 40-60 bpm
* Delays the transmission of action potentials
* Purkinje fibers 20-30 bpm
* Can act as pacemakers under some conditions
Intrinsic Conduction System
* Autorhythmic cells:
* Initiate action potentials
* Have “drifting” resting potentials called pacemaker potentials
* Pacemaker potential – membrane slowly depolarizes “drifts” to threshold, initiates action potential, membrane repolarizes to -60 mV.
* Use calcium influx (rather than sodium) for rising phase of the action potential
Physiology of cardiac muscle
The heart is composed of three major types of cardiac muscle.
1- The atrial muscle.
2- The ventricular muscle.
3- Specialized excitatory and conductive muscle fibers; an excitatory system of the heart that helps spread of the impulse (action potential) rapidly throughout the heart.
