Heart histology

Gross anatomy

Early embryology

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 sinuatrial 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).

Cardiac myocytes

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 fibers 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.

Specialized cardiomyocytes

The rhythmic contraction of the heart is completely independent of conscious effort. The specialized cardiomyocytes that facilitate this feature are the sinuatrial node, atrioventricular node and the Purkinje fibres. Unlike average cardiomyocytes, these cells have inherently leakage 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 sinuatrial node cells are more easily depolarized than the atrioventricular node and Purkinje fibres. Therefore, it will be the first to become depolarized. The sinuatrial 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 sinuatrial 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 sinuatrial 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.

Histological layers

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.