Question 2: Outline the major functions, histology, location and ultra-structure of cardiac muscle tissue

*These posts are from coursework answers for my degree, but the Figures that are referred to in the text didn't scan well and have already been handed in. These long posts would probably not interest most people but if you enjoy quite in-depth reading of scientific problems then this may be for you.

Question 2: Describe with the aid of diagrams the histology, ultrastructure, location, and function of cardiac muscle tissue.

Answer:

The heart itself is a hollow organ consisting of four chambers, weighing approximately 250g to 350g. The uppermost chambers are smaller and contribute little to the forceful expulsion of blood from the heart. These are called the right and left atria. Below these atria are the ventricles, which are much more muscular and exert a great deal of pressure upon blood during their contraction. The right and left atria of the heart are divided by the interatrial septum, a relatively thin wall of muscle. The ventricles are separated by a thicker wall of muscle termed the interventricular septum. The four chambers operate as two individual pumps; the right atrium and ventricle pump deoxygenated blood to the lungs, while the left atrium and ventricle pump oxygenated blood to the rest of the bodily tissues. The heart is covered by the pericardium, a thick wall consisting of two layers, namely, the fibrous pericardium (outer layer) and the serous pericardium (inner). The serous pericardium is further sub-divided into three thin layers, the parietal layer, the pericardial cavity, and the visceral layer. The function of the cavity between these other two layers is to allow the heart to experience relatively low friction, so that its efforts of pumping are made more efficient and much less damage is caused by the repeated rubbing together of the two separated layers. The visceral layer of the serous pericardium is also known as the epicardium and forms one of three parts of the heart wall. The other parts are called the myocardium (muscle cells of the heart) and the endocardium. The epicardium is frequently thought of as being the outer layer of the heart, with the other previously mentioned layers being the external protective membranes enclosing it. The epicardium consists of one sheet of squamous epithelial cells on top of fragile connective tissue.  The endocardium is the innermost layer of the heart wall, it too is composed of squamous endothelial cells resting on delicate connective tissue.  This is the layer that rests on the surface of each of the chambers of the heart (Jardins, 2008, pp. 188-193).

The myocardium however, is of great importance for this piece of work. It is the relatively thick layer of the heart wall that is composed of cardiac muscle cells. These cardiac muscle cells make up most of the heart and it is their job to ensure that blood building up in the ventricles are subjected to a high enough level of pressure to be propelled around both the body and lungs during contraction of the heart. The heart muscles weave together, producing characteristic shapes of either bundles or spirals that create a network, joining all areas of the heart together. The general arrangement of cardiac muscle is illustrated in figure 2.1. This overall assembly is called the fibrous skeleton of the heart, and reinforces the structural integrity of the inner myocardium (Jardins, 2008, p. 192). The force produced by the contraction or shortening of the myocardial fibres in the ventricles is called the myocardial contractility.  When this force increases, the condition is called positive ionotropism, with negative ionotropism being the inverse (Jardins, 2008, pp. 210-211).

Cardiac muscle tissue is exclusively found within the heart. Its task is to contract forcibly, ensuring that blood is pumped throughout the body, where it can deliver nutrients and oxygen to body cells, especially those respiring at relatively high rates. It differs from skeletal muscle, and shares some similarity with many smooth muscle types in that it produces its own contractions, i.e. cardiac muscle tissue is autorhythmic. Cardiac tissue is also not controlled voluntarily. While the average human being can affect his or her heart rate indirectly by choosing which activities to engage in, what foods and drinks to consume (caffeine being a strong stimulus for increasing the heart rate) and by controlling their rate of breathing, the contractions of the heart are not controlled directly. One cannot decide to make their heart beat at a certain rate simply by willing it to occur. Cardiac muscle cells are cylindrical in shape and branch out, forming connections with one another called intercalated disks. They are typically 100-500 micrometres in length and 12-20 micrometres in diameter. Their nucleus or nuclei are centrally located, but most cardiac muscle cells only contain a single nucleus, with 2 being uncommon. They are striated, and capable of their own spontaneous contractions without nervous innervation. (Seeley, Vanputte, Regan and Russo, 2011, pp. 275-276). The basic structure of cardiac muscle cells are shown in figure 2.2. In this diagram the striations are clearly shown.

Desmosomes are also present within cardiac muscle which helps bind the cells together. Desmosomes are attachments formed by protein which extend fibres into the cytoplasms of two adjacent cells, acting as an anchor that prevents the cells from drifting apart. They are highly useful for bridging gaps between skeletal or cardiac muscle cells as these types of cell undergo considerable stresses which would tear them apart if their junctions were weak. The intercalated disks separating cardiac cells contain gap junctions which serve the purpose of propagating action potentials, similar to myelin sheaths which surround nerve cells in the brain. This occurs because gap junctions contain proteins called connexons which allow small molecules and ions to pass through them. For this reason, gap junctions are highly useful for the transmission of electrical impulses (Pack, 2001, pp. 24-25). Both of these structures and others are shown in figure 2.3. The action potentials are comparable between both neurons and cardiac muscle cells, except that cardiac muscle action potentials last longer, followed by a longer period (as compared to skeletal muscle and nerve cell duration) in which the resting potential occurs, this may also be described by saying that the cardiac muscle fibres are in their polarised state (this length of time is called the refractory period), as shown by Seeley, VanPutte, Regan and Russo (2011), p. 309. While the fibres of the heart cells are in this resting state, there is an electrical charge difference between the inside of the cardiac muscle cells and the extracellular fluid. This difference in charge is called the resting membrane potential or RMP. This is largely due to the electrolytes potassium, sodium and calcium (Jardins, 2008, p. 397-398).

Ordinarily, there is close to 40x the concentration of potassium ions contained within the cardiac cell than outside of it.  However, the inside of the cell only contains about 1/20 the concentration of sodium ions and 1/5 the concentration of calcium ions compared to the outside of the cell membrane. This large difference in electrolyte concentrations causes potassium ions to leave the cardiac cell and sodium ions to enter. However, potassium ions find it very easy to diffuse out of the cell while sodium ions have more difficulty permeating the membrane. The result is that roughly 50-75 potassium ion may leave for every sodium ion that enters. The product of this situation is a relative negativity of the cardiac cell in relation to its outside environment, due to so many positive ions leaving the cell. This results in the RMP previously described, giving the cell a charge of approximately -90 mV (Jardins, 2008, pp. 397-399). 

Normally, the muscle fibres of the cardiac ventricles may be stimulated to contract between 60 and 100 times per minute (i.e. the resting heart rate). There are 5 main phases of the action potential in cardiac muscle cells. These are shown below, and in figure 2.4.

Phase 0; the early phase, or phase of rapid depolarization is the prompt for cardiac muscle contraction and begins due to reception of an electrical impulse propagated from the sinoatrial, or SA node of the heart. This impulse encourages the mass influx of sodium ions into the cardiac cell through specific sodium ion channels and results in a net voltage of +30 mV. This overall event is termed depolarisation. The rise in voltage of the membrane potential is very rapid, as shown by the steep upward curve in the diagram, which is labelled with a zero.

Note the label of the threshold value which is at a very low value on the graph, barely higher than -90 mV. This shows that cardiac muscles cells are sufficiently excitable to be stimulated for contraction without much influence from pacemaker cells.

The phases following phase 0 mark specific stages that the cells go through in order to repolarise and regain their resting membrane potential.

Phase 1; the initial repolarisation, will occur in which potassium ions leave the cell, lowering its electrical difference to roughly +10 mV. This is a relatively quick process but continued repolarisation is prevented by the next phase, this is why the downward movement marked by a one on the diagram is short-lived.

Phase 2; the plateau state, calcium ions move into the cell, and lower the outward diffusion of potassium ions, resulting in a slower rate of repolarisation and consequently prolonged state of stimulation for the cell. This causes the myocardial cells to contract for a longer period of time than other cells that operate by a similar mechanism, for example, neurons and skeletal muscle cells.

Phase 3: the final rapid depolarisation, at point, the diffusion of calcium ions into the cell stops occurring and the potassium ions once again flow rapidly out of the cell, causing it to reach an electrical difference of -90 mV once again with its surrounding environment.

Phase 4: the resting / polarised state. Finally, sodium, potassium and calcium ion pumps cause all of the ions to return to their normal concentrations, allowing the cell to once again become stimulated to contract (Jardins, 2008, pp. 399-400).

The specially adapted pacemaker cells of the heart have the ability to generate their own action potential without external stimulation. Parasympathetic and sympathetic stimulation from the nervous system can slow down or speed up cardiac contractions, but the heart muscles are capable of contracting by themselves.

Figure 2.5 shows the conductive system of the heart. The electrical cycle is initiated at the sinoatrial (SA) node, also known as the pacemaker of the heart, which is located in the right atrium. The impulse produced here is conducted through both the right and left atria. In the former, it travels through the anterior, middle, and posterior intermodal tracts, which join at the atrioventricular (AV) junction. The left atrium receives its electrical impulses via the Bachmann’s bundle which conducts it from the SA node. Both of these atria contract at the same time, which pumps blood into their respective ventricles. At this point, the AV junction transmits the signal along the bundle of His and into the ventricles. This bundle separates (shown at the bottom of figure 2.5) into two separate bundle branches which consist of Purkinje fibres which spread along the apex (base of the heart) and direct themselves towards the heart’s base. (Jardins, 2008, pp. 402-403).

The heart is required to pump blood through both the pulmonary and systemic circulatory systems. Blood is pumped to the lungs via the right ventricle, and to all other tissues from the left ventricle. The atria are involved in these contractions, but to a relatively low extent, and thus are routinely ignored due to consideration of the ventricles. Given the much greater distance of blood travel that the left ventricle must support, it contains more cardiac muscle cells and pumps blood at a higher pressure. When the blood travels around the body, waste products such as carbon dioxide diffuse into the blood stream, possibly binding to haemoglobin, and are transported ultimately to the right ventricle of the heart, where they can be taken to the lungs and breathed out. According to Seeley, VanPutte, Regan and Russo (2011), p. 675, there are 4 main functions of the heart which are shown below.

Firstly, the generation of blood pressure, which is produced by the forceful contractions of the cardiac muscle. Without this blood pressure the blood would either not travel the full distance along blood vessels to the cells of the body and lungs, or would travel slowly enough to lead to pathology. This condition is known as circulatory hypoxia and can occur for a few different reasons, but in this specific case the sluggish movement of blood through peripheral blood vessels can lead to inadequate unloading of oxygen molecules in order to oxygenate tissues. These tissue cells will undergo metabolic reactions at roughly their normal rate, but the slowly moving red blood cells will have already lost oxygen molecules, causing a reduced oxygen pressure gradient between them and the respiring cells. Thus, oxygen will be delivered to the tissue at a reduced rate, resulting in hypoxia (elaborated upon by Jardins, 2008, p.261).

Secondly, the separation of blood returning from and travelling to, both the pulmonary and system circulatory systems. This allows deoxygenated blood to become oxygenated by travelling through the lungs, and then subsequently be pumped around the body. The result of this is that there is a greater efficiency in the transport of oxygen and waste products around the body, than if these two circulations were combined.

Thirdly, blood is kept flowing in its intended direction. This is achieved by valves present in the heart that prevent the backflow of blood. If this were not the case then blood could pool inside the heart without reaching its necessary destination.

Lastly, the heart controls the supply of blood to other cells in the body as a whole (lungs included). The pressure and frequency of cardiac muscle cell contraction regulates the amount of blood passing tissue at any given time. This allows the heart to change condition of blood flow based on how much oxygen / nutrients are needed by other cells, and how much waste must be removed from these cells as well. During exercise for example, a person’s bodily cells would both require more oxygen and nutrients to be delivered to respiring tissue, as well as needing more carbon dioxide and related metabolic by-products to be removed at the same time. Such a circumstance calls for a higher rate and forcefulness of cardiac muscle cell contraction, i.e. an increase in both frequency and myocardial contractility, with the latter also known as positive ionotropism.  Both of these factors increase the cardiac output, i.e. the amount of blood that is pumped by the blood per unit of time.

The equation for cardiac output (CO) is given below:

CO = HR x SV

Where HR is heart rate and SV is stroke volume. The heart rate is determined by many factors such as blood pressure and sympathetic and parasympathetic stimulation of cardiac muscle, whereas stroke volume is mainly controlled by the following three factors: ventricular preload, ventricular afterload, and contractility of myocardial cells (Jardins, 2008, p. 209).

The term ventricular preload describes the extent to which myocardial fibres stretch before contracting (at the end of diastole). Under normal circumstances, the greater the stretching, the greater the force of contraction and resultant cardiac output (Jardins, 2008, p. 209).

Ventricular afterload then, is the force that the ventricles must overcome in order to pump blood. This is determined by the viscosity and volume of blood that must be pumped, the resistance of peripheral blood vessels, and the cross-sectional area of lumen that the blood is pumped into. This information explains the left ventricular hypertrophy experienced in atherosclerosis. The systolic pressure of arteries is increased in order to compensate for a reduced vessel lumen due to the build-up of atherosclerotic plaque, which means that the left ventricle must work harder in order to overcome a greater resistive force (ventricular afterload) and pump blood around the body. The introduction of a stent in an affected artery increases the size of the lumen, decreasing the resistance experienced by the blood and reducing the effort of the left ventricle, among other benefits. (Jardins, 2008, pp. 209-210).

Finally, contractility of the myocardium, has been mentioned briefly above as the force produced by the shortening (or contraction) of muscle fibres in the ventricles.

Given the chief importance of cardiac function in the body, it is vital that the heart be able to produce energy from various different sources. Schmidt (2000, p. 119) explains that the heart is more than capable of breaking down ketones and fatty acids, even when glucose is adequately present, for its energy requirements.

A rough formula for estimating how fast a heart may beat at its maximum frequency is shown below:

Maximum heart rate = 220 – age

Thus, we can see that there is a general rule that as one ages, the maximum frequency of heart rate decreases. While beyond the scope of this article, the reasons for this are interesting to note briefly. The reasons for why aging may decrease maximum heart rate are possibly that as age increases, oxygen supply to heart muscle increases, or that compliance in heart cells decreases with age, or also, that there is an increase in connective tissue infiltrating SA and AV junctions, as well as bundle branches (Jardins, 2008, pp. 387-388).

Question 2 References:

Jardins, T.D., 2008. Cardiopulmonary Anatomy & Physiology Essentials of Respiratory Care 5^th ed. USA, NY: Nelson Education, Ltd.

Mescher, A.L., 2013. Junqueira’s Basic Histology Text & Atlas, 13^th ed. China: The McGraw-Hill Companies.

Pack, P.E., 2001.  Anatomy and Physiology, Hoboken, NJ: Wiley Publishing, Inc.

Schmidt, F., 2000. Biochemistry II, New York, NY: Wiley Publishing, Inc.

Seeley, R.R, VanPutte, C.L., Regan, J. and Russo, A.F., 2011. Seeley’s Anatomy & Physiology, 9^th ed. New York, NY: McGraw-Hill.