Histology of the Heart
The heart is a critical organ that keeps blood moving throughout the body. Blood is an important medium that not only carries nutrients and oxygen throughout the body, but it also collects waste products and returns them to the liver and kidney for further processing and excretion.
The heart is able to achieve this autonomy based on its histological make-up. The organ is comprised of specialized conductive tissue that can generate an action potential independent of the nervous system. This article will look at the early embryology of the heart (not including cardiac origami), review the basic gross anatomy, and discuss the cellular architecture and histological arrangement of the organ. Clinically relevant points will also be discussed.
Mono-nucleated, with the nucleus centrally placed and numerous mitochondria located in the cytoplasm
Features: sarcomeres, intercalated discs, gap junctions, desmosomes, fascia adherens
Features: leaky ion channels, fewer myofibrils, reduced potential resistance
Cells: sinoatrial node, atrioventricular node, Purkinje fibers
Endocardium: simple squamous epithelium with the subendocardial tissue found underneath
Myocardium: cardiomyocytes are branched and it is highly vascularized
Epicardium: double layer of connective tissue surrounding the heart in the mediastinum
The heart is a muscular, four-chambered system that is responsible for pumping blood through the vascular network. The organ is located within the thoracic cavity in a region known as the mediastinum. It is bordered bilaterally by the lungs, anteriorly by the sternum and posteriorly by the oesophagus and thoracic vertebra.
The heart is composed of left and right atria and ventricles. The atria are superior to (and less muscular than) the ventricles. The right and left atria are receptacles for blood coming from the body and lungs, respectively. On the other hand, the right and left ventricles eject blood from the heart to the lungs and body, respectively. As a result of this arrangement, the right side of the heart contains oxygen poor blood, while the left side contains oxygen rich blood. Under normal conditions, blood from the left and right sides of the heart does not mix. This separation is achieved by the interatrial and interventricular septum (both of which are continuous with each other) that runs roughly along the midline of the heart.
There are two sets of valves located in the heart:
- The atrioventricular valves regulate one way passage of blood from the atria to the ventricles. The mitral valve is located on the left side of the heart, while the tricuspid valve is found on the right side.
- The outlet valves allow blood to leave the heart to one of two destinations. From the right side of the heart, blood leaves the right ventricle and passes through the pulmonary valve to gain access to the lungs via the pulmonary arteries . On the left side of the heart, blood leaves the left ventricle and passes through the aortic valve to perfuse the entire body via the derivative vessels of the aorta.
The action potential responsible for cardiac contraction is generated primarily from the sinoatrial node, located near the orifice of the superior vena cava. The impulse is transmitted across the atria and to the atrioventricular node, where it then depolarizes the ventricles via the bundle of His and associated Purkinje fibres.
The development of the heart coincides with the increased nutrient demand of the embryo to the extent where the yolk sac is no longer an ideal nutritional source. A cluster of cells known as progenitor heart cells aggregate in the region cranial to the primitive streak in the epiblast layer of the embryo. After these cells migrate from the epiblast layer to the splanchnic layer, they become the primary heart field. These cells settle as a semi-circular cluster of cells cranial to the neural folds. The primary heart field cells are destined to form both left and right atria, the left ventricle, and majority of the right ventricle.
About 20 days after the primary heart field cells appear, the secondary heart field develops in the splanchnic mesoderm. They will form the remainder of the right ventricle, as well as the great vessels that take blood away from the heart. Once the definitive primary heart field has been formed, the cells then differentiate, under the influence of neighbouring pharyngeal endoderm, into cardiac myoblasts. Myoblasts are early progenitor cells that differentiate into muscle cells. Cardiac myoblasts specifically differentiate into myocardiocytes, which makes up the myocardium (muscular layer of the heart). Of note, there are two other types of muscle fibres not discussed in this article (smooth and striated). Additionally, primary heart field cells also form islands of blood that will later participate in vasculogenesis.
The primary and secondary heart fields undergo significant folding that transforms the clusters of cells into the cardiac tube, and subsequently the familiar four-chambered heart. As these changes occur, the myocardium produces excess extracellular matrix containing a lot of hyaluronic acid that creates a partition between it and the adjacent endothelium.
The heart contains three basic layers similar to those seen in arteries and veins. The outermost layer is the epicardium, which is derived from the proepicardium (from the septum transversum). The middle layer is the myocardium, and the innermost layer is the endocardium, which originated from mesothelial cells of the outflow tract.
There are two major “pacemaker” centres in the heart that automatically generate an action potential. These are specialized myocardiocytes that depolarize more rapidly than surrounding cells. The chief pacemaker of the heart is the sinoatrial node. These cells were originally part of the sinus venosus (quadrangular cavity that preceded the right atrium). Their migration to a region adjacent to the opening of the superior vena cava was facilitated by the absorption of the sinus venosus into the right atrium. The atrioventricular node is the secondary pacemaker site of the heart. It is continuous with the bundle of His and both are derived from atrioventricular canal cells and sinus venosus cells (particularly those from its left wall).
Unlike skeletal muscle cells, cardiomyocytes are usually mono-nucleated; although there are some instances where di- or multinucleated cells have been encountered. The nuclei are also centrally located within the cylindrical cell. The cytoplasm of the cardiomyocyte (sarcoplasm) contains a large number of mitochondria to meet the high metabolic demand of the cells.
There are repeating units of contractile fibres known as sarcomeres. Each sarcomere is made up of thin and thick myofilaments known as actin and myosin, respectively. Bundles of myofilaments (myofibrils) extend across the length of the cell. The myofilaments are bordered on either side by dense Z lines that can be observed intersecting light areas of the cell known as I bands. As a result of the regularly repeating contractile units (sarcomeres), cardiac tissue has a distinct striated appearance (due to alternating I bands and dark regions known as A bands) on light microscopy, much like skeletal muscle tissue.
Each cardiomyocyte is attached to its neighbouring cell via intercalated disks. These are densely stained ends of the cell that are heavily populated by desmosomes, gap junctions and fascia adherens. Gap junctions permit rapid transmission of action potentials from one cell to the other. They extend across the membranes of juxtaposed cells, creating direct pathways for ions to flow. This allows all the cells of the heart to contract in synchrony. The desmosomes and fascia adherens are anchoring proteins that hold the myofibrils and the cardiomyocyte’s cytoskeleton in place.
The rhythmic contraction of the heart is completely independent of conscious effort. The specialized cardiomyocytes that facilitate this feature are the sinoatrial node, atrioventricular node and the Purkinje fibres. Unlike average cardiomyocytes, these cells have inherently leaky ion channels that result in easier depolarization. Furthermore, there are fewer myofibrils in the heart conductive tissue than there is in the contractile tissue. Consequently, there is less resistance in these cells, making it easier for an action potential to flow through them. The reduction in resistance is further compounded by the fact that these cells are somewhat wider than their contractile counterparts, allowing for free flow of the stimulus.
The sinoatrial node cells are more easily depolarized than the atrioventricular node and Purkinje fibres. Therefore, it will be the first to become depolarized. The sinoatrial node cells will also repolarize and generate another action potential before the atrioventricular node cells or Purkinje fibres have a chance to do so in a normal heart. This arrangement results in electrical flow being generated at the sinoatrial node, spreading across the atria (resulting in atrial contraction), then passing to the atrioventricular node.
There is an insulating fibrous annulus at the atrioventricular junction across the heart (except at the atrioventricular node) that prevents the action potential from randomly crossing from the atria to the ventricle. The atrioventricular node also has fewer gap junctions and utilizes slow calcium channels in its depolarization process. Consequently, the action potential is delayed at the atrioventricular node; giving the recently depolarized ventricle time to recover.
Although the heart’s rhythm is intrinsically regulated, both the sinoatrial node and atrioventricular node can be modified by the sympathetic and parasympathetic systems. The resulting effect is a change in inotropy (strength of contraction of the heart) and chronotropy (the rate of contraction). The sympathetic pathway will increase the inotropy and chronotropy, while the converse is achieved by the parasympathetic nervous system.
Like the vessels that branch from it, the heart has three distinct histological layers. The abluminal surface is called the epicardium; which is also the visceral component of the pericardium. The luminal surface is known as the endocardium, and the myocardium is the muscular layer that resides between the other two layers.
The endocardium can be compared to the tunica intima of blood vessels. It forms the luminal surface of the heart and is composed of simple squamous epithelium. Deep to the endocardium is the subendocardial tissue, which contains loose vascularized connective tissue. The subendocardial tissue also contains nerves as well as Purkinje fibres. In areas where the myocardium is thin (i.e. atria) the endocardium is relatively thicker.
Like the muscular tunica media, the myocardium is the middle layer of the heart that contains a large quantity of muscle cells. As opposed to the unbranched linear appearance of muscle cells in skeletal muscle tissue, cardiomyocytes are arranged in a branched, linear manner. This layer is highly vascularized and the cardiomyocytes contain glycogen granules as an additional energy source.
The pericardium is a fibrous double layered connective sheath that encases the heart within the mediastinum. The visceral portion (that is in contact with the heart) is called the epicardium. It is a mesothelium derivative that is rich in adipocytes and neurovascular tissue. This layer is well lubricated, which facilitates smooth movement of the heart against the parietal pericardium during contraction.
There are several adaptive mechanisms employed by different organs to handle a stressful environment. For muscle tissue, they increase in size with increasing systemic demand. Cardiomyocytes respond in a similar manner to a prolonged increase in peripheral resistance. Cardiac hypertrophy secondary to essential hypertension is the most common form of cardiac enlargement observed in medical practice.
Essential hypertension is characterized by an increase in peripheral vascular resistance (reflected in an increased systolic and diastolic blood pressure) that makes it more difficult for the heart to pump blood throughout the body. The amount of myofibrils within the cardiomyocytes increases, resulting in an increase in the size of the cells. Typically, the left ventricle undergoes concentric hypertrophy. However, right ventricular hypertrophy and even atrial hypertrophy, can be observed in late stages of the disease.
Hypoxic Injury & Myocardial Infarction
The heart is constantly beating from intrauterine development and only stops when an individual is deceased. This heavy work load requires a constant supply of oxygen and nutrients as well as a shuttle to get rid of generated waste. Blood is delivered to cardiac tissue via the coronary arteries (which arise from the root of the aorta). Unfortunately, these arteries can become obstructed by plaque formation (atherosclerosis) or as a result of an embolus (originating from deep vein thrombosis, atrial fibrillation, etc). The loss of blood supply results in hypoxic injury to the cardiomyocytes that – if it is not resolved immediately – can result in death of the tissue within the region.
This process is the core aspect of a myocardial infarction. Classically, patients present with pressing, burning, or crushing retrosternal pain that radiates up the left side of the chest, neck and shoulder. Some individuals may experience symptoms of indigestion, with epigastric pain. There are hallmark changes on electrocardiography that a clinician should look out for if this is the suspected lesion (ST- segment elevation are characteristic of MI, but may be absent). Pathologically, the remaining tissue is firm and maintains the typical cell structure for that tissue, but the nucleus of the cell is destroyed. This is the hallmark feature of coagulative necrosis that follows infarction of any organ, except brain tissue (which undergoes liquefactive necrosis). Furthermore, the American Heart Association recommends measuring cardiac troponin as a confirmatory test for a myocardial infarction.