Table of Contents
Physiology of the Heart
Being the central element of blood circulation, the heart is responsible for maintaining constant blood circulation in the body. It also participates in the regulation of blood pressure by responding to changes in blood volume by adjusting the force and frequency of its contractions. ANP (atrial natriuretic peptide) is a hormone produced in the right atrium, which regulates the water and salt levels of the body when the atrium is stretched. This results in more water being excreted by the kidneys in order to reduce blood volume and blood pressure.
Anatomy of the Heart
Before going into the depths of physiology, we should first recapitulate the structure of the heart. The heart is a muscular, hollow organ that is situated in the mediastinum in the chest. Two ventricles and two atria (singular: atrium) comprise the four chambers of the heart. The aortic and pulmonary valves separate the ventricles from the aorta and pulmonary artery, respectively. The ‘right’ heart supplies the lungs with blood, while the ‘left’ heart supplies blood to the rest of the body.
The heart consists of specialized muscle tissue known as the myocardium. There is also a separating layer of connective tissue between the atria and the ventricles called the cardiac skeleton. The innermost lining of the heart is known as the endocardium, whereas the epicardium constitutes the outer lining. The solid, protective capsule surrounding the heart is called the pericardium (lat. endo, myo, epi, peri). The upper region of the heart, to which major vessels are attached, is called the base of the heart (basis cordis) (‘base’ does not refer to the bottom of the heart, as one might think), and the lower portion is referred to as the apex (apex cordis).
Blood supply to the heart
Two major vessels, namely, the left and right coronary arteries, supply blood to the heart. Both coronary arteries originate from the aorta (aortic sinus) that lies behind the aortic valve. The heart supplies its fibers with a part of the expelled oxygen-rich blood.
Excitation and the electrical conduction system of the heart
Autorhythmicity and electrical conduction in the heart are unique features of the cardiac muscle. This muscle belongs to the group of striated muscles. Contrary to skeletal muscles, the cardiac muscle cannot be voluntarily controlled.
The beating of the heart occurs due to muscle contraction. Specialized muscle cells in the myocardium, known as pacemaker cells, spontaneously generate electrical impulses. This cellular network is, therefore, referred to as the excitation and electrical conduction system; the remaining muscle cells stimulated by this contraction constitute the working myocardium.
Pacemaker cells have no resting membrane potential; however, they can spontaneously depolarize. They generate action potentials at regular intervals (pacemaker cells in the sinus node can generate 60–80 impulses/minute). The sinus node is referred to as the primary pacemaker.
In the case of a sinus node dysfunction (e.g., due to a myocardial infarction caused by a vascular obstruction preventing oxygen supply), the atrioventricular (AV) node sets the cardiac rhythm to 40–55 beats/min. As the tertiary pacemaker, the conduction system (bundle of His, His-Tawara bundle, Purkinje fibers) in the ventricles can set a rhythm up to 25–40 beats/min.
The heart at a glance
- Endocardium, myocardium, epicardium, pericardium
- Right ventricle
- Left ventricle
- Right atrium
- Left atrium
- Heart valves (mitral, pulmonary, tricuspid, and aortic valves)
- Base and apex
- Left and right coronary arteries
Excitation and electrical conduction systems
- Sinus node
- Atrioventricular node (AV node)
- Bundle of His
- His-Tawara bundle
- Purkinje fibers
Prof. Joseph Alpert describes the anatomical structures of the human heart in the lecture “Anatomy of the Heart.”
You can watch the full lecture here: Cardiology.
Mechanics of the Heart
The cardiac cycle consists of systole, during which blood is expelled from the heart, and diastole, during which the heart fills passively with blood via muscle relaxation. The systole is divided into the contraction and ejection phases, while the diastole is divided into the relaxation and filling phases.
During the filling phase, if the pressure within the ventricles exceeds that within the atria, the atrioventricular valves (mitral and tricuspid) close. During the contraction phase, all valves are closed when the ventricles begin to contract. This phenomenon is referred to as isovolumetric contraction (‘iso’ means equal, referring to a constant volume during contraction), during which, the pressure within the heart increases.
The ejection phase begins with the opening of the semilunar valves (aortic and pulmonary valves) after the ventricular pressure exceeds the pressure within the aorta and pulmonary trunk. This is an auxotonic contraction, during which the ventricular pressure increases and, at the same time, the ventricular volume decreases. This pressure-volume change can be described using Laplace’s law as follows:
K = Ptm * (r / 2 * d),
where K = wall tension, Ptm = transmural pressure, r = ventricular radius, d = wall thickness. With a decrease in the ventricular volume and the radius of the ventricle, the thickness of the wall increases. Therefore, with constant tension in the walls, the transmural pressure increases, which allows auxotonic contraction. During systole, the valve plane is pulled toward the apex owing to the attachment of the pericardium to the diaphragm.
The relaxation phase commences with the closing of the semilunar valves. Isovolumic relaxation time is defined as the time interval between the completion of aortic ejection and the beginning of ventricular filling. If the ventricular pressure falls below the pressure within the atria, the AV valves open.
During diastole, the valve plane returns to its initial position, which makes the AV valves cover the blood volume of the atria, thus reaching almost maximum filling of the ventricles (80–90%). This process is called a valve plane mechanism. Furthermore, atrial contraction causes the filling of the ventricles during the filling phase (10–20%). After the AV valves close, a new cycle begins.
Excitation and Electrical Conduction Systems
All cells of the working myocardium are connected to each other via gap junctions, creating the so-called functional syncytium. The electrical impulses generated by the pacemaker spread to the atria. The connective tissue of the cardiac skeleton provides electrical insulation between the atria and the ventricles. The AV node is responsible for conducting electrical impulses to the ventricles.
At this point, the AV node plays the role of a ‘brake’ and slows down the further conduction of impulses. Consequently, the ventricles contract after the atria, which explains the typical pumping rhythm of the heart that is seen in images. The muscle fibers of the conduction system comprise the bundle of His, His-Tawara bundle, and Purkinje fibers, which rapidly conduct impulses through the ventricles leading to their contraction.
In the event of a third-degree atrioventricular block, the conduction function of the AV node enables the ventricles and atria to contract independent of each other. This phenomenon can be observed in ECGs as separate curves with independent rhythms. If the intrinsic rhythm of the ventricular pacemaker is inadequate to bring about the contraction of the cardiac chambers, the use of a pacemaker is suggested. A temporary interruption or slowing down of conduction results in a first-degree or second-degree atrioventricular block.
Cardiac Action Potential
The action potentials generated by the pacemaker cells are significantly different from those generated by the working myocardium. This topic is worth your attention because it is a popular exam subject.
Pacemaker cells are capable of the autonomic excitation of the working myocardium owing to their ability to depolarize spontaneously. After the excitation of the cells and repolarization, the membrane potential does not attain a static resting potential (as is the case with other cell types); rather, the cell slowly begins to depolarize again. This process is called slow diastolic depolarization (SDD) because it takes place during diastole when the heart muscles are not contracting.
A special, voltage-gated ion channel in the pacemaker cells (called HCN channel or ‘funny channel’) enables SDD. These cells repolarize up to -60 mV, resulting in slow diastolic depolarization during which, the membrane potential becomes positive again owing to the influx of sodium and potassium ions. The threshold potential (potential for opening) of the HCN channel is -40 mV.
Once this threshold is reached, the channels open and Ca2+ ions enter the cells. A rapid increase in Ca2+ conductivity triggers an action potential. The voltage-gated potassium channels allow K+ ions to flow out of the cell, following which, the membrane potential becomes negative and the cell repolarizes. A new cycle begins at -60 mV.
Important: The duration of an action potential varies depending on the excitation system and is attributed to the different number of ion channels in the cells. The action potential lasts the longest in the Purkinje fibers.
The action potential generated in the working myocardium is different from that in the pacemaker cells.
In contrast to the pacemaker cells, the cells of the working myocardium have a stable resting membrane potential of -85 mV during diastole. It is sustained by potassium flux through the voltage-gated potassium channels.
If an electric impulse is received from the pacemaker cells at this point, the potassium channels begin to close and the membrane potential becomes more positive. Once the threshold potential of -65 mV is attained, the voltage-gated sodium channels open and sodium flows rapidly into the cell, resulting in the generation of an action potential. Repolarization initially begins in the voltage-gated calcium channels (L-type Ca2+) and finally reaches resting membrane potential after the reopening of the potassium channels. The influx of calcium is also an important signal transmitter for electromechanical coupling, ensuring that cells are not only excited but also contracted.
Action potential in the heart at a glance
An action potential in the pacemaker cells has the following characteristics:
- No stable resting membrane potential
- Slow diastolic depolarization
- Depolarization through calcium influx
- Varied duration
An action potential in the working myocardium has the following characteristics:
- Prolonged duration (300 ms)
- Resting potential/plateau phase
- Extremely rapid depolarization
- Depolarization through sodium influx
Electromechanical coupling describes the transformation of an incoming electrical signal (in the form of an action potential) into a mechanical contraction of the cardiac muscle. It is similar to the electromechanical coupling in the skeletal muscle but differs fundamentally in one key point.
In cardiac muscle cells, calcium efflux from the sarcoplasmic reticulum is responsible for the intracellular increase in calcium, which is necessary for the contraction of the cardiac muscle. In comparison, in the skeletal muscle, a mechanically coupled receptor (dihydropyridine receptor) in the cell membrane causes an increase in intracellular calcium during depolarization.
Hyperkalemia and Hypokalemia
Understanding the influence of the electrolyte concentration of blood on heart rhythm is essential not only for an examination but also in clinical practice. The concentration of K+ in and around the cardiac muscle affects the conductivity of the potassium ion channels and, therefore, the excitation of the cardiac muscle.
Elevated potassium levels (hyperkalemia, > 5.0 mmol/L) can lead to the reduced excitability of the working myocardium, cause cardiac arrhythmia, and may even lead to cardiac arrest. Potassium deficiency (hypokalemia, < 3.6 mmol/L) also leads to cardiac arrhythmia but in a ‘more active’ manner; the symptoms include ventricular extrasystoles and ventricular fibrillation.
An electrocardiograph records electric fields on the surface of the skin. Electric fields are created by the transfer of charges during the electrical activity in the heart and are represented in the ECG by the differences in potential. The ECG only provides information about the electrical activity and involution in the myocardium and not about its mechanical activity.
The mathematical vector that describes the strength and direction of the electric field points from the excited to the unexcited cells.
According to Einthoven, the limb leads are bipolar.
According to Goldberger, the limb leads are unipolar. With the help of an operational amplifier circuit, two electrodes are connected to an indifferent electrode at a high level of resistance.
This knowledge allows us to understand the basics of the voltage curve in an ECG. The current resulting vector is projected onto the respective limb lead. If a vector is perpendicular to the direction of a limb lead, the potential difference measured in this limb lead is 0 mV, as the scalar product (the projection of one vector onto another) is 0.
If a vector is parallel to the limb lead, its total value is measured as a potential difference.
The basics of ECG
All students should familiarize themselves with the basics of ECG. Memorizing the description and significance of each component will help in the interpretation of abnormal ECGs.
- P wave: Excitation spreading in the atrial myocardium
- PQ interval: AV node conduction (200 ms)
- QRS complex: Excitation spreading in the ventricular myocardium
- R peak: Ventricular excitation spreading from the base to the apex (assessment of the heart’s electrical axis)
- ST segment: Ventricles are excited
- T wave: Repolarization of the ventricular myocardium
- QT interval: Approximate duration of an action potential (300–400 ms)
- Isoelectric line: Fully excited or unexcited myocardium (zero potential)
The common irregularities that can be detected using an ECG are as follows:
- First-degree atrioventricular block: PQ interval is extended (200 ms)
- Second-degree atrioventricular block: Not every QRS complex is followed by a P wave
- Third-degree atrioventricular block: P waves and QRS complex appear independently, but regularly, from each other
- Ventricular extrasystoles: Deformed and broadened ‘formless’ QRS complexes
- Myocardial infarction: Elevation of the ST segment
- Blockage of the ventricular conduction system: Broadened QRS complex; the heart’s electrical axis is altered
Control of Cardiac Activity
The Frank-Starling mechanism
The heart can adapt to short-term changes in pressure and volume via the Frank-Starling mechanism (intracardiac) and vegetative innervation (extracardiac).
Autonomic nervous system
The autonomic nervous system regulates the performance parameters of the heart. The neurotransmitters of the sympathetic and parasympathetic nervous systems activate signaling pathways in the myocardium, which affect both pacemaker cells and the working myocardium and influence cardiac output. The most important factors affecting cardiac output are as follows:
- Heart rate (chronotropic)
- Force of contraction (inotropic)
- Conduction speed (dromotropic)
The parasympathetic nervous system regulates cardiac activity via the neurotransmitter, acetylcholine, which slows the heart rate. Muscarinic (acetylcholine) receptors are present in the atria; parasympathetic effects are weak in the ventricles. Acetylcholine binds to the muscarinic receptors (M2) and activates the Gi protein.
As a result of the signaling cascade, the potassium channels open and the SDD of the pacemaker cells extends. The action potential occurs after some delay and the heart rate decreases.
The sympathetic nervous system releases noradrenaline and adrenaline, which increase the heart rate. The ventricles are innervated only by the sympathetic nerves. The neurotransmitter binds to the β-1 adrenergic receptors and activates G proteins (Gs protein). As a result, the sodium and calcium channels open even wider. The increased sodium conductivity leads to rapid action potentials, which causes an increase in the heart rate. The additional calcium flux supports electromechanical coupling and the force of contraction increases.
The autonomic nervous system of the heart at a glance
|Sympathetic nervous system||Parasympathetic nervous system|
|Positive chronotropic effect||Negative chronotropic effect|
|Positive dromotropic, positive inotropic, positive lusitropic, and positive bathmotropic effects||Negative dromotropic and negative bathmotropic effects|
|Neurotransmitter: Noradrenaline, adrenaline, β-1 receptors, Gs protein; sodium conductivity +, calcium flux +||Neurotransmitter: Muscarinic acetylcholine receptors (M2), Gi protein; potassium conductivity +|
The effect of the sympathetic and parasympathetic nervous systems on the heart is an important examination topic. Studying the signaling pathways of the different receptors will help understand their pharmacology more easily, especially the activity of cardiotropic substances. Beta-blockers (e.g., metoprolol) decrease the heart rate and the force of contraction and are indicated in the treatment of coronary heart disease and arterial hypertension.
Blood and Oxygen Supply to the Heart
The cardiac muscle needs a continuous and adequate supply of oxygen to maintain a consistent force of contraction. The heart requires about 10% of the oxygen in the body (10–50 mL/min depending on whether it is at rest or stress). The cardiac muscle uses about 70% of the oxygen transported by the blood (compared to 25% used by the rest of the body). Therefore, an increased oxygen demand during physical activity is met by the increased blood flow to the coronary arteries. Coronary blood flow can increase fivefold during exercise.
The left and right coronary arteries split and form numerous anastomoses with each other. In the case of thrombosis or stenosis in one of the coronary arteries, collateral circulation cannot adequately supply the myocardium with oxygenated blood. This leads to ischemia (oxygen deficiency), which is a medical emergency. If unattended, it may lead to necrosis of the heart tissue and myocardial infarction.