Physiology of the Heart

 

                                                                    Majid Ali, M.D.

The heart exists to pump oxygen to all cell populations of the body. Just as a water pump functions well if it pumps clean water and an air pump functions well if it pumps clean air, the heart functions well and remains healthy it pumps clean blood. So, heart coronary disease is a problem of the circulating blood, which has two guardian angels: the spirit (sun) and the bowel (soil). That simply stated, is my Sun-Soil Model of Heart Health.

Oxygen drives electron transfer events in human biology. Electrons generate electromagnetic energy fields. Energy fields regulate all redox-related phenomena and oxygen homeostasis. Energy (voltage) changes as biomembranes open or close ion channels in membranes. Changes in ionic concentration inside the cells trigger, amplify or otherwise modify the behavior of proteins. Proteins are workhorses—some working as catalysts driving metabolic pathways, others serving as messengers. Proteins travel with lipids, sugars, and redox-restorative molecular species, and communicate with them at different levels of form and function. Changes in some proteins switch genes on or off. Genes, in turn, encode for other proteins that are essential for cellular replication, differentiation, and demise. The heart is an elegant example of that oxygen order of human biology. Every facet of oxygen homeostasis is clearly reflected in the workings of the heart. It is a muscular electromagnetic device designed to assure that every cell in the body is delivered its required oxygen needs, moment by moment, year after year. All acquired acute and chronic cardiac states are but varying reflections of disorder in that oxygen order of human biology.

Two Hearts, One Lung

The heart is a single organ only on the surface, though structurally it is encased within a single pericardial sac and its four chambers are strongly enjoined. Functionally, it is a different story. The right and left atria, its upper two chambers, work in unison —as a single neuromuscular entity—while the same holds for the right and left ventricle located below the upper chambers. When the two atria act synergistically —a functional characteristic assured by a structural syncytium of myocardial fibers that make up their wall—the blood flows from the right atrium into the right ventricle through the tricuspid valve and from the left atrium to the left ventricle through the bicuspid (mitral) valve. Functionally, the heart works as two organs in yet other way. The “right heart”—comprising right atrium and right ventricle—pushes venous, deoxygenated blood to the lungs via pulmonary arteries. Similarly, the “left heart”—comprising left atrium and left ventricle— pumps oxygenated blood it receives from the lungs to the arterial tree via the aorta.

In contrast to the heart, the lungs—though structurally distinct and located on either side of the heart —work as a single functional unit. From a pathophysiologic point, the essential functions of ventilation, oxygenation of blood, disposal of carbon dioxide and other volatile waste substances are served in identical fashion and to similar degrees in both lungs. The same holds for “neuro-pulmonary” regulatory functions. Individuals who lose one of the lungs abruptly during surgery—for resection of neoplasm, for instance— rapidly adjust to the loss of that organ without suffering clinically significant long-term consequences. The remaining lung, of course, hypertrophies to compensate for the surgically absent pulmonary parenchyma. Henry Gray’ Gray’s Anatomy10 and Arthur Guyton’s Human Physiology and Mechanisms of Disease11 are two highly recommended texts for detailed study of the anatomy and physiology of the heart.

The cavity of the right atrium can contain up to two ounces of blood and is larger than that of the left atrium. Its walls are thinner than those of the left atrium. The right ventricle can accomodate about three ounces of blood and forms most of the front surface of the heart, located behind the sternum. The left ventricle is larger and has a thicker wall than the right ventricle, the ratio of thickness between the two being 3:1. It forms the apex of the heart and most of the posterior surface. The cusps of the mitral valve are anchored to the wall of the left ventricle through thick muscular structures called chordae tendineae. Uncommonly, infarction of the muscle in those structures leads to rupture of chordae tendineae and acute incompetence of the valve and subsequent acute heart failure.

 

The Heart’s Transistors

In transistors, the electron flow through a semiconductor is governed by the voltage applied to one of the electrodes. The semiconductor essentially serves as a channel for the transfer of electrons while the electrode at the site of the change in voltage serves as the ‘gate’ of that channel. Biomembranes of microbes and humans house proteins that essentially function as field-effect transisters, and are designated as voltage-gated ion channels. Application of appropriate voltage imposed across biomembranes cause those channels to open and allow a current of ions—energetically, a wave of energy —to cross through the membrane. During the early 1950s, Hodgkin and Huxley described the conceptual functional model of such channel proteins.12 Recently, the structure and function of voltage-gated ion nchannels has drawn intense scrutiny.13-18 Indeed, It was only in 2003 that the x-ray structure of a potassium ion channel was made visible and tests of a hypothesis for voltage-sensor motion described by the Nobelist MacKinnon and colleagues.19,20

Three types of cell membrane channels play critical roles in nodal excitation and conducting phenomena:

1. Fast sodium channels;

2. Slow calcium-sodium channels; and

3. Potassium channels.

The speed of electron and ion transfer during the creation and conductance of action potentials (propagating energy waves) is astounding. Opening of the fast sodium channels for a few 10,000ths of a second results in massive influx of positively charged sodium ions with a quick spike-like onset of action potential (up to +20 mV) which creates an observable contraction of the ventricular myocyte.This is followed by a plateau-like action potential (from +20 to about -10 mV) at the cell membrane produced by much slower opening of the slow calcium-sodium channels. The plateau-like action potential lasts for a few tenths of a second. The cycle is completed when potassium channels open at the end of that period, permitting a rapid movement of positively charged potassium ions out of the cell, thus restoring the original ‘resting’ level of the electrical state.

The sinus nodal fibrils fuse with atrial myocytes to provide fast conductance of action potentials directly to the atrial musculature in its entirey. The propagating energy pulses of the nodal fibrils—again, potential in the prevailing electrophysiology parlance—spread throughout the atrial walls, much like the ripples move through the surface of the still water of a pond when a child hurls a stone in it. One of the sites to which the energy field spreads from the sinus node—at a velocity of about 0.3 m/sec—is the atrioventricular node located in the posterior septal wall of the right atrium immediately behind the tricuspid valve. In addition to that general slower spread, there are also routes of faster motion (about 1 m/sec) of the energy pulse through specialized atrial fibers called internodal pathways. The slight delay during that travel confers a physiologic advantage: It gives the ventricles some additional time to fill up further through atrial contraction before the ventricles contract.

The A-V node links the atrial myocytes to the ventricular musculature through right and left bundles of Purkinje cell. The action potentials of the ventricular cells are faster both in development and dissipation than those of the sinus node. This is due to the lower negativity (-55 to -60 mV) of the sinus node than of the ventricular fibers (due to the natural membrane leakiness of some of the nodal cells as described above). On the inside aspect of the cell membrane, the ‘gates’ of the fast sodium channel remain closed when the value is -60 mV or greater.

The Deplorization- Repolarization Cycle of the Cardiac Myocyte

The depolarization-repolarization cycle of a cardiac myocyte is a continuum. It may be divided into the following phases for the conceptual understanding of the clinical significance of derangements of the cycle:

A. A theoretical ‘energized resting’ phase;

B. A phase of initiation of deplorization;

C. A phase of completion of depolarization;

D. A theoretical ‘intermission’ phase;

E. A phase of initiation of replorization; and

F. A phase of completion of repolarization.

Those phases are schematically expressed in the five parts of Figure 4 (1-5). Again, it is important to recognize thatenergetically both the states of positivity and the so-called ‘negativity’ are electrically-charged energy states.Specifically, a negative value indicates a concentration of electrons. Thus, when the surface of a cell is designated as ‘negative’ in the various phases, it does not signify an ‘energy deficit state’—an energy ‘hole,’ so to speak—on the cell membrane. The confusion caused by term electronegativity can be avoided by the terms “electronicity” and “hyperelectronicity” for the states of electron density and hyperpolarization respectively. The same holds for the cell interior.

A. The Theoretical ‘Energized Resting’ Phase

In the theoretical energized resting phase, a cardiac myocyte carries a negative charge on its interior —in reality, a strong ‘electron-dense’ state—while its surface is positively charged (Figure 4.A). Since the surface of the cell membrane carries a similar charge throughout, two electrodes of a galvanometer applied to two different regions of the cell surface will not register a differentail, and hence will not show a deflection on the meter.

Figure 4.1

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B. The Phase of Initiation of Depolarization (Beginning of the Action Potential)

The term depolarization refers to a process of charge reversal. The commencement of depolarization involvesconversion of the positive charge on the surface of a segment of the membrane to a negative charge—with the flow of electron energy from the energized cell innards and the development of a positive charge in the interior of the cell corresponding to that region of the surface as shown in 4.B. In this state, one section of the cell membrane has depolarized while the remaining cell has not. If one of the electrode is applied to the deploarized area while the other is placed on the remaining surface not affected by the action potential yet—the original ‘un-deploarized’ state—the meter will register a differenetial between the two areas and record positively—an upward swing. For example, when the action potential (energy wave) illustrated above involves the atrial musculature, it produces an upward deflection recognized as the first part (upswing) of the P wave on the electrocardiogram. The P wave of the lectrocardiogram precedes atrial contraction.

Figure 4. 2

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C. A Phase of Completion of Depolarization;

This phase represents when the process of the reversal of charges on the cell membrane and cell interior (deploraization) has been completed as illustrated in Figure 4. C. As the electrical change involves the full length of the cell membrane, the two electrodes of the galvanometer cease to register any differential between the two areas. Thus, no current flows and meters displays a return to the original state (following a downward deflection). In the case of the atrial P wave, the process of completion of depolarization is represented by the second (downswing) portion of the P wave.

Figure 4.3

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The Theoretical ‘Intermission’ Phase

Under physiologic conditions, the interval between the completion of depolarization and the commencement of repolarization is only a theoretical intermission, and actually represents a continued state of the completed depolarization phase. It is of significance only when the depolarization-repolarization continuum is interrupted by ion channel dysfunction. Schematically, the Figure 4. C also pertains to this state.

E. A Phase of Initiation of Replorization (Charge Reversal to the Original ‘Resting’ State

The term repolarization also refers to the process of charge reversal but in a direction opposite to that observed during depolarization. Specifically, it is reversal of changes that occurred on the cell surface as well its interior during deploarization. As in the case of depolarization, the change in thee lectrical charge does not take place instantly throughout the cell membrane and the cell interior. Rather, the process begins with one segment of the cell surface and then spreads to involve the surface in its entirety. The initiation of repolarization is illustrated in Figure 4. D)

Figure 4. 4

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Again, as in the case of the initiations of depolarization, two electrodes applied to two different regions will register a charge differential and the recorder will exhibit a deflection. However, the direction of the electrical charge change in this case will be opposite (downswing) to that observed during depolarization. In the case of atrial motion, the recorder deflection during atrial reploarization—the so-called atrial T wave—is masked by the much stronger QRS complex of ventricular action potentials.

F. A Phase of Completion of Replorization

This phase represents when the process of the reversal of charges on the cell membrane and cell interior created by deploraization has been completed and the original ‘resting’ phase has been completed. As the electrical change now involves the full length of the cell membrane, the two electrodes of the galvanometer cease to register any differential between the two areas. Thus, no current flows and meters displays a return to the original state. In the case of the atrial P wave, the process of completion of depolarization is represented by the second (upswing) portion of the atrial T wave. As for the surface and interior charges are concerned, this state is schematically expressed in Figure 4. E . Of course, this is the same state as shown in Figure 4. A, representing the completion of the depolarization-repolarization cycle and full return to the original ‘resting’ state.

Figure 4.5

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The Hyperpolarization State

Hyperpolarization is a state in which the negative charge in the cell interior is stronger than that under ordinary conditions (Figure 4. F). This state is significant under both physiologic and pathologic conditions. Physiologically, in the case of the sinus node the potassium channels remain open for a few tenths of seconds after the termination of atrial action potential, permitting a large outflow of positively charged potassiom ions, thus leaving the cell interior hyperpolarized—with a higher level of ‘negativity.’ As a result the energized resting membrane potential is brought down to about -55 to -60, as indicated earlier. The physiologic vagal effect on the heart is mediated by a simliar effect on potassium membranes—acetylcholine increases permeability of the fiber membrane to potassium ions which flow out, leaving behind a cell interior with higher level of negativity—and consequently less prone to depolarization. Not unexpectedly, the state of hyperpolarization slows the heart rate. Under pathophysiolgic stresses, the vagal effect can slow the heart rate to dangerously low levels, even threatening cardiac standstill and death.

4. F. Hyperpolrization

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Some Leaky Cell Membranes Preserve Life—others Assure Death

How does the sinus node auto-excite? That simple question gives a glimpse of Nature’s ingeniuty in creating a pacemaker for the heart that performs flawlessly for over one hundred years in many people. Nature made the membranes of some nodal fibrils naturally leaky. That membrane permeability charactristically allows a continous flow of positively charged sodium into the cells, thus increasing the membrane potential. Thus, the energized resting potential of the nodal fibrils continues to rise. (As mentioned ealier, there is really no true ‘resting’ potential in those cells.) Influx of sodium ions eventaully raises the resting potential to a threshold voltage of about -40 mV at which the calcium-sodium channels open—allowing a rapid flush into the cell of both calcium and sodium ions and the consequent discharge.

The natural nodal cell membrane leakiness to sodium ions can be expected to have a flip side. Specifically, why does it not lead to a disastrous state of persistent depolarization in the sinus node—with consequent unremitting contraction of myocardium? The answer to that question provides a second fascinating glimpse into Nature’s elegance of design and sense of economy. The calcium-sodium channels close within about 100 to 150th milliseconds, as the stimulus for their opening abates, preventing further influx of sodium and calcium ions. Concurrently, potassium channels open permitting a rapid efflux of potassium ions from the cell innards. The movement of potassium leads to rapid change in the inside charge—excess negativity within the cell—producing s state of hyperpolarization. That state of hyperpolarization pulls the ‘resting’ membrane potential down to about -55 to -60 mV as the action potential terminates.

The next question concerns the fate of the hyperpolarization state. Specifically, why does it not persist? Potassium channels again! Those openings close within few tenths of a second after the action potential is over preventing further efflux of potassium ions. Enter the naturally leaky cell membranes again! Sodium again begins to leak inward, moving the ‘resting’ potential upward until it reaches the threshold voltage of -40 mV. Auto-excitation of some nodal cells begins again, initiating another cycle. My grandfather lived to be over 100 years. He never suffered from any heart disorder. That means his sinus node created 100,000 action potentials every day of the month, every year of his life. That was the amazing miracle of his ‘leaky’ sodium channels in his sinus nodal fibrils. Those ‘leaky’ membranes served my grandmother equally well, for she lived for over ninety years without any heart disease.

The Cardiac Cycle and Electrocardiography

All events occurring from the commencement of one heartbeat to the beginning of the next are collectively designated as the cardiac cycle. In essence, the cycle comprises a phase of relaxation (diastole), during which the heart chambers fill with blood, followed by a phase of cardiac contraction (systole) during which the blood is pumped into the pulmonary arteries from the right heart and into the aorta from the left ventricle. The volume of blood in each ventricle at the end of diastole in healthy adults—designated as the end-diastolic volume—ranges from 110 to 120 milliliters (ml). During ventricular contraction, the bulk of that volume (about 70 ml) is pumped out. That constitutes stroke volume output.That, of course, means that a significant volume of ventricular contents (about 40 ml) remains in the ventricular cavities at the end of systole. That volume is designated as the end-systolic volume. The difference between the end-diastolic and end-systolic volumes—the stroke volume output, as pointed out earlier—is clinically used as an indicator of the pump efficiency of the heart. Thus, the portion of the end-diastolic volume that is pumped (about 60%) is referred to as the ejection fraction. In the states of increased demand for oxygen—during physical exercise, anemia, and others—the heart responds by dramatically increasing cardiac output. The increased blood flow into a normal heart can increase the end-diastolic volume to as much as 150 to 180 ml, whereas increased force of contraction can reduce end-systolic volume to as low as 10 to 20 ml. Together those changes can rapidly increase the cardiac pumping capability by 300 to 400 percent of the resting values.

The heart sounds heard with a stethoscope are produced by valvular activities during the cardiac cycle. Sine the valve openings are essentially passive, such events do not produce audible sounds. By contrast, during valve closures their vanes are brought together forcibly by sudden changes in the pressure differentials across them, which also create additional vibrations by turbulence in the blood in close vicinity of valves. The first heart sound is produced by the relatively slower closure of the atrioventricular (A-V) valves whereas the the second heart sound is generated by rapid snapping together of the cusps of the aortic and pulmonary valves. That explains why the first heart sound is of low pitch and longer lasting, while the second sound is of higher pitch and lasts for a shorter period of time.

For individuals with well-preserved cardiovascular homeostasis, the aortic pressure during systole rises to a level of 100 to 120 mm Hg and falls to 65-75 mm Hg during diastole. That lateral pressure exerted on the walls of the aorta by the blood contained in it during systole and diastole are designated as the systolic and diastolic aortic blood pressures. The pressures of the blood in brachial arteries—measured clinically at the elbows with mercury monometers—is, for practical purposes, the same as in the aorta during the cardiac cycle. Mercury monometers have been replaced in advanced countries with a variety of modern electronic pressure transducer devices, which do not have the disadvantages of mercury—a metal which has a considerable inertia (and is slow to respond), and is also highly toxic. The basic design of transducers involves the use of thin and highly stretched metal membranes that permit conversion of pressure changes into electrical signals to be recorded on high-speed electrical recorders.

Each cardiac cycle is initiated by the ‘spontaneous’ generation of an action potential in the sinus node—not a spontaneous event in reality, in light of the continuum of the sodium ion transfer during to the intrinsic ‘leakiness’ of some nodal fibrils, as described earlier. The nodal potential spreads throughout the atrial musculature and triggers its contraction, with consequent ‘pumping’ of atrial contents into the ventricles, the so-called ‘priming the ventricular’. The atrial impulse (action potential) takes about one-tenth of a second to travel from its atrial nodal origin to the ventricles, thus providing for a slight but valuable delay in the ventricular contraction, which creates a robust pressure as it pumps blood throughout the arterial tree. However, atrial contraction contributes only ten to fifteen percent of the ventricular volume. Thus, the loss of atrial pacing in atrila fibrillation is tolerated by most people for long periods without significant loss of myocardial performance. Ventricular fibrillation, by contrast, is often fatal when not arrested expediently.

The electrocardiogram in health is a record of the electrical energy generated by the heart activity through one cycle and recorded by a set of electrodes placed at specific sites on the skin of the limbs and the chest wall. It comprises an initial deflection designated the P wave followed by a sequence of three deflections designated as the “QRS complex” which, in turn, is followed by the last deflection named the T wave. The P wave is produced by the electrical energy wave (potential) generated as the atria depolarize prior to their contraction. Similarly, the QRS deflections are electrical pulses produced by the spreading of the depolarizating pulse throughout the ventricles prior to their contraction. The T wave is produced by potentials generated as the ventricles recover from their state of depolarization. Under physiologic conditions, this process usually takes 0.25 to 0.35 seconds after ventricular depolarization.

Since an electrocardiogram reflects all energetic events occurring during a complete cardiac cycle, of necessity it must include both depolarization and repolarization phases. In that context, as outlined above, the P wave and QRS complexes represent depolarization waves while the T wave is a record of venrricular repolarization. The repolarization deflection of the atria —designated atrial T wave—is hidden beneath the QRS complex.

Figure 6. The Pattern of Electrical Energy Pulses (an Electrocardiogram) Generated by a Single Cardiac Cycle Is Illustrated

 

 

 

 

 

 

 

Figure 44-10

1,2,3 / Stein

 

 

 

 

 

 

Autonomic Neurocircuitry of the Heart

The study of anatomic and functional characteristics of the cardiac autonomic neurocircuitry reveals valuable insights into the workings of the heart. Safety first. That must be accepted as the prerequisite of all mechanical designs. Safety in the operation of a machine calls for a fast-responding braking system while the gas-pedal function can be slow to gear up without significant drop in the long-term functionality of the unit. Teleologically, it might be expected that the cardiac autonomic circuitry would exhibit a similar basic design. That, indeed, is the case. The parasympathetic system essentially serves as the fast-acting braking system of the heart, while the sympathetic drive may be rightfully seen as the gas pedal. That design serves the heart well as it responds to minute-by-minute changes occurring within the body as well as those in its immediate environment. The heart was not designed to be a trigger-happy organ. The faster parasympathetic and slower sympathetic influences blend to assure that. The problems, of course, begin when that delicate autonomic balance is repeatedly put in jeopardy by unrelenting adrenergic hypervigilence, as well as cholinergic disturbances cuased by diverse pathophysiologic factors. The issues of chronic anger and unrelenting sadness are paramount among those factors.

What are the anatomic and neurochemical bases of faster-acting parasympathetic and slower sympathetic pulses? The question is discussed at length in a later chapter entitled “Oxidative Dysautonomia.” Below, I briefly present the anatomic and functional aspects of cardiac autonomic circuitry to shed some light on the subject.

The parasympathetic supply to the heart comes through the vagus nerves, while the sympathetic innervation is provided through sympathetic chains. The parasympathetic nerves are predominantly distributed to to the sinus and atrioventricular nodes, with limited supply to the ventricular musculature. By contrast, the sympathetic nerves directly reach all segments of the heart, with a particularly strong representation in the ventricles. Furthermore, the parasympathetic outflow is of high frequency (with consequent rapid conduction), whereas the sympathetic discharges are of low frequency, with the resulting slower rate of transmission.

The chemical basis of parasympathetic influences involves the release of acetylcholine at the vagal endings, which greatly increases the permeability of cardiac myocyte membranes to potassium. The expected result is rapid leakage of potassium out of the conductive fibers. That results in increased ‘negativity’ (stronger negative electrical charge) inside the cells—a phenomenon designated as hyperpolarization. That state markedly reduces the tissue excitability—makes the excitable tissue much less excitable.

The chemical basis of sympathetic influences is the release of catecholamines at the sympathetic endings with the following main effects:

1. Increase in the rate of sinus nodal discharges;

2. Increases in the speed of conduction;

3. Increase in the level of excitability; and

4. Increase in the force of contraction.

In light of those functional characteristics of the autonomic fibers in the heart, the anatomic aspects of the basic design of cardiac neurocircuitry provides an extra level of safety in the gas-pedal/brake-pedal dynamics of the heart. Thus, the parasympathetic focus on the excitatory and conducting system provides for more prompt and effective responses than the sympathetic innervation of the ventricular musculature. Furthermore, the parasympathetic outflow is of higher frequency than that of the sympathetic signaling. That—as discussed in the later chapter entitled “Oxidative Dysautonomia” —contributes to yet additional levels of safety in the autonomic homeostasis of the heart, and in the functions of the other body organs.

 

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