Cardiology: Anatomy and histology

Gross anatomy and histology of the heart

Gross anatomy of the heart

The heart consists of four chambers. Blood flows into the right atrium via the superior and inferior venae cavae. The left and right atria connect to the ventricles via the mitral (two cusps) and tricuspid (three cusps) atrioventricular (AV) valves, respectively. The AV valves are passive and closed when the ventricular pressure exceeds that in the atrium. They are prevented from being everted into the atria during systole by fine cords (chordae tendineae) attached between the free margins of the cusps and the papillary muscles, which contract during systole. The outflow from the right ventricle passes through the pulmonary semilunar valve to the pulmonary artery, and that from the left ventricle enters the aorta via the aortic semilunar valve. These valves close passively at the end of systole, when ventricular pressure falls below that of the arteries. Both semilunar valves have three cusps.
The cusps or leaflets of the cardiac valves are formed of fibrous connective tissue, covered in a thin layer of cells similar to and contiguous with the endocardium (AV valves and ventricular surface of semilunar valves) and endothelium (vascular side of semilunar valves). When closed, the cusps form a tight seal (come to apposition) at the commissures (line at which the edges of the leaflets meet).
The atria and ventricles are separated by a band of fibrous connective tissue called the annulus fibrosus, which provides a skeleton for attachment of the muscle and insertion of the valves. It also prevents electrical conduction between the atria and ventricles except at the atrioventricular node (AVN). This is situated near the interatrial septum and the mouth of the coronary sinus and is an important element of the cardiac electrical conduction system.
The ventricles fill during diastole; at the initiation of the heartbeat the atria contract and complete ventricular filling. As the ventricles contract the pressure rises sharply, closing the AV valves. When ventricular pressure exceeds the pulmonary artery or aortic pressure, the semilunar valves open and ejection occurs. As systole ends and ventricular pressure falls, the semilunar valves are closed by backflow of blood from the arteries.
The force of contraction is generated by the muscle of the heart, the myocardium. The atrial walls are thin. The greater pressure generated by the left ventricle compared with the right is reflected by its greater wall thickness. The inside of the heart is covered in a thin layer of cells called the endocardium, which is similar to the endothelium of blood vessels. The outer surface of the myocardium is covered by the epicardium, a layer of mesothelial cells.
The whole heart is enclosed in the pericardium, a thin fibrous sheath or sac, which prevents excessive enlargement. The pericardial space contains interstitial fluid as a lubricant.

Structure of the myocardium

The myocardium consists of cardiac myocytes (muscle cells) that show a striated subcellular structure, although they are less organized than skeletal muscle. The cells are relatively small (100 × 20 μm) and branched, with a single nucleus, and are rich in mitochondria.
They are connected together as a network by intercalated discs (Figure 2.2), where the cell membranes are closely opposed. The intercalated discs provide both a structural attachment by ‘glueing’ the cells together at desmosomes, and an electrical connection through gap junctions formed of pores made up of proteins called connexons. As a result, the myocardium acts as a functional syncytium, in other words as a single functional unit, even though the individual cells are still separate. The gap junctions play a vital part in conduction of the electrical impulse through the myocardium.
The myocytes contain actin and myosin filaments which form the contractile apparatus and exhibit the classic M and Z lines and A, H and I bands (Figure 2.3). The intercalated discs always coincide with a Z line, as it is here that the actin filaments are anchored to the cytoskeleton. At the Z lines the sarcolemma (cell membrane) forms tubular invaginations into the cells known as the transverse (T) tubular system. The sarcoplasmic reticulum (SR) is less extensive than in skeletal muscle and runs generally in parallel with the length of the cell (Figure 2.4). Close to the T tubules the SR forms terminal cisternae that with the T tubule make up diads (Figure 2.5), an important component of excitation–contraction coupling. The typical triad seen in skeletal muscle is less often present. The T tubules and SR never physically join, but are separated by a narrow gap. The myocardium has an extensive system of capillaries.

Coronary circulation

The heart has a rich blood supply, derived from the left and right coronary arteries. These arise separately from the aortic sinus at the base of the aorta, behind the cusps of the aortic valve. They are not blocked by the cusps during systole because of eddy currents, and remain patent throughout the cardiac cycle. The right coronary artery runs forward between the pulmonary trunk and right atrium, to the AV sulcus. As it descends to the lower margin of the heart, it divides to posterior descending and right marginal branches. The left coronary artery runs behind the pulmonary trunk and forward between it and the left atrium. It divides into the circumflex, left marginal and anterior descending branches.
There are anastomoses between the left and right marginal branches and the anterior and posterior descending arteries, although these are not sufficient to maintain perfusion if one side of the coronary circulation is occluded.
Most of the blood returns to the right atrium via the coronary sinus, and anterior cardiac veins. The large and small coronary veins run parallel to the left and right coronary arteries, respectively, and empty into the sinus. Numerous other small vessels empty into the cardiac chambers directly, including thebesian veins and arteriosinusoidal vessels.
The coronary circulation is capable of developing a good collateral system in ischaemic heart disease, when a branch or branches are occluded by, for example, atheromatous plaques. Most of the left ventricle is supplied by the left coronary artery, and occlusion can therefore be very dangerous. The AVN and sinus node are supplied by the right coronary artery in the majority of people; disease in this artery can cause a slow heart rate and AV block.

Vascular anatomy

The blood vessels of the cardiovascular system are for convenience of description classified into arteries (elastic and muscular), resistance vessels (small arteries and arterioles), capillaries, venules and veins. Typical dimensions for the different types of vessel are illustrated (Figure 3.1).

The systemic circulation

Arteries

The systemic (or greater) circulation begins with the pumping of blood by the left ventricle into the largest artery, the aorta. This ascends from the top of the heart, bends downward at the aortic arch and descends just anterior to the spinal column. The aorta bifurcates into the left and right iliac arteries, which supply the pelvis and legs. The major arteries supplying the head, the arms and the heart arise from the aortic arch, and the main arteries supplying the visceral organs branch from the descending aorta. All of the major organs except the liver are therefore supplied with blood by arteries that arise from the aorta. The fundamentally parallel organization of the systemic vasculature has a number of advantages over the alternative series arrangement, in which blood would flow sequentially through one organ after another. The parallel arrangement of the vascular system ensures that the supply of blood to each organ is relatively independent, is driven by a large pressure head, and also that each organ receives highly oxygenated blood.
The aorta and its major branches (brachiocephalic, common carotid, subclavian and common iliac arteries) are termed elastic arteries. In addition to conducting blood away from the heart, these arteries distend during systole and recoil during diastole, damping the pulse wave and evening out the discontinuous flow of blood created by the heart’s intermittent pumping action.
Elastic arteries branch to give rise to muscular arteries with relatively thicker walls; this prevents their collapse when joints bend. The muscular arteries give rise to resistance vessels, so named because they present the greatest part of the resistance of the vasculature to the flow of blood. These are sometimes subclassified into small arteries, which have multiple layers of smooth muscle cells in their walls, and arterioles, which have one or two layers of smooth muscle cells. Resistance vessels have the highest wall to lumen ratio in the vasculature. The degree of constriction or tone of these vessels regulates the amount of blood flowing to each small area of tissue. All but the smallest resistance vessels tend to be heavily innervated (especially in the splanchnic, renal and cutaneous vasculatures) by the sympathetic nervous system, the activity of which usually causes them to constrict.

Arterial anastomoses

In addition to branching to give rise to smaller vessels, arteries and arterioles may also merge to form anastomoses. These are found in many circulations (e.g. the brain, mesentery, uterus, around joints) and provide an alternative supply of blood if one artery is blocked. If this occurs, the anastamosing artery gradually enlarges, providing a collateral circulation.
The smallest arterioles, capillaries and postcapillary venules comprise the microcirculation.

Veins

The venous system can be divided into the venules, which contain one or two layers of smooth muscle cells, and the veins. The veins of the limbs, particularly the legs, contain paired semilunar valves which ensure that the blood cannot move backwards. These are orientated so that they are pressed against the venous wall when the blood is flowing forward but are forced out to occlude the lumen when the blood flow reverses.
The veins from the head, neck and arms come together to form the superior vena cava, and those from the lower part of the body merge into the inferior vena cava. These deliver blood to the right atrium, which pumps it into the right ventricle.
The one or two veins draining a body region typically run next to the artery supplying that region. This promotes heat conservation, because at low temperatures the warmer arterial blood gives up its heat to the cooler venous blood, rather than to the external environment. The pulsations of the artery caused by the heartbeat also aid the venous flow of blood.

The pulmonary circulation

The pulmonary (or lesser) circulation begins when blood is pumped by the right ventricle into the main pulmonary artery, which immediately bifurcates into the right and left pulmonary arteries supplying each lung. This ‘venous’ blood is oxygenated during its passage through the pulmonary capillaries. It then returns to the heart via the pulmonary veins to the left atrium, which pumps it into the left ventricle. The metabolic demands of the lungs are not met by the pulmonary circulation, but by the bronchial circulation.
This arises from the intercostal arteries, which branch from the aorta. Most of the veins of the bronchial circulation terminate in the right atrium, but some drain into the pulmonary veins.

The splanchnic circulation

The arrangement of the splanchnic circulation (liver and digestive organs) is a partial exception to the parallel organization of the systemic vasculature (see Figure 3.1). Although a fraction of the blood supply to the liver is provided by the hepatic artery, the liver receives most (approximately 70%) of its blood via the portal vein. This vessel carries venous blood that has passed through the capillary beds of the stomach, spleen, pancreas and intestine. Most of the liver’s circulation is therefore in series with that of the digestive organs. This arrangement facilitates hepatic uptake of nutrients and detoxification of foreign substances that have been absorbed during digestion. This type of sequential perfusion of two capillary beds is referred to as a portal circulation. A somewhat different type of portal circulation is also found within the kidney.

The lymphatic system

The body contains a parallel circulatory system of lymphatic vessels and nodes. The lymphatic system functions to return to the cardiovascular system the approximately 8 L/day of interstitial fluid that leaves the exchange vessels to enter body tissues.
The larger lymphatic vessels pass through nodes containing lymphocytes, which act to mount an immune response to microbes, bacterial toxins and other foreign material carried into the lymphatic system with the interstitial fluid.

Vascular histology and smooth muscle cell ultrastructure

Larger blood vessels share a common three‐layered structure.
Figure 4.1 illustrates the arrangement of these layers, or tunics, in a muscular artery.
A thin inner layer, the tunica intima, comprises an endothelial cell monolayer (endothelium) supported by connective tissue. The endothelial cells lining the vascular lumen are sealed to each other by tight junctions, which restrict the diffusion of large molecules across the endothelium. The endothelial cells have a crucial role in controlling vascular permeability, vasoconstriction, angiogenesis (growth of new blood vessels) and regulation of haemostasis. The intima is relatively thicker in larger arteries and contains some smooth muscle cells in large and medium‐sized arteries and veins.
The thick middle layer, the tunica media, is separated from the intima by a fenestrated (perforated) sheath, the internal elastic lamina, mostly composed of elastin. The media contains smooth muscle cells embedded in an extracellular matrix (ECM) composed mainly of collagen, elastin and proteoglycans. The cells are shaped like elongated and irregular spindles or cylinders with tapering ends and are 15–100 μm long. In the arterial system, they are orientated circularly or in a low‐pitch spiral, so that the vascular lumen narrows when they contract. Individual cells are long enough to wrap around small arterioles several times.
Adjacent smooth muscle cells form gap junctions. These are areas of close cellular contact in which arrays of large channels called connexons span both cell membranes, allowing ions to flow from one cell to another. The smooth muscle cells therefore form a syncytium, in which depolarization spreads from each cell to its neighbours.
An external elastic lamina separates the tunica media from the outer layer, the tunica adventitia. This contains collagenous tissue supporting fibroblasts and nerves. In large arteries and veins, the adventitia contains vasa vasorum, small blood vessels that also penetrate into the outer portion of the media and supply the vascular wall with oxygen and nutrients.
These three layers are also present in the venous system but are less distinct. Compared with arteries, veins have a thinner tunica media containing a smaller amount of smooth muscle cells, which also tend to have a more random orientation.
The protein elastin is found mainly in the arteries. Molecules of elastin are arranged into a network of randomly coiled fibres. These molecular ‘springs’ allow arteries to expand during systole and then rebound during diastole to keep the blood flowing forward. This is particularly important in the aorta and other large elastic arteries, in which the media contains fenestrated sheets of elastin separating the smooth muscle cells into multiple concentric layers (lamellae).
The fibrous protein collagen is present in all three layers of the vascular wall and functions as a framework that anchors the smooth muscle cells in place. At high internal pressures, the collagen network becomes very rigid, limiting vascular distensibility. This is particularly important in veins, which have a higher collagen content than arteries.

Exchange vessel structure

Capillaries and postcapillary venules are tubes formed of a single layer of overlapping endothelial cells. This is supported and surrounded on the external side by the basal lamina, a 50–100 nm layer of fibrous proteins including collagen, and glycoproteins.
Pericytes, isolated cells that can give rise to smooth muscle cells during angiogenesis, adhere to the outside of the basal lamina, especially in postcapillary venules. The luminal side of the endothelium is coated by glycocalyx, a dense glycoprotein network attached to the cell membrane.
There are three types of capillaries, and these differ in their locations and permeabilities.
Continuous capillaries occur in skin, muscles, lungs and the central nervous system. They have a low permeability to molecules that cannot pass readily through cell membranes, owing to the presence of tight junctions which bring the overlapping membranes of adjacent endothelial cells into close contact. The tight junctions run around the perimeter of each cell, forming a seal restricting the paracellular flow of molecules of molecular weight (MW) 10 000. These junctions are especially tight in most capillaries of the central nervous system and form an integral part of the blood–brain barrier.
Fenestrated capillaries are much more permeable than continuous capillaries. These are found in endocrine glands, renal glomeruli, intestinal villi and other tissues in which large amounts of fluid or metabolites enter or leave capillaries. In addition to having leakier intercellular junctions, the endothelial cells of these capillaries contain fenestrae, circular pores of diameter 50–100 nm spanning areas of the cells where the cytoplasm is thinned. Except in the renal glomeruli, fenestrae are usually covered by a thin perforated diaphragm.
Discontinuous capillaries or sinusoids are found in liver, spleen and bone marrow. These are large, irregularly shaped capillaries with gaps between the endothelial cells wide enough to allow large proteins and even erythrocytes to cross the capillary wall.

Smooth muscle cell ultrastructure

The cytoplasm of vascular smooth muscle cells contains thin actin and thick myosin filaments (Figure 4.2). Instead of being aligned into sarcomeres as in cardiac myocytes, groups of actin filaments running roughly parallel to the long axis of the cell are anchored at one end into elongated dense bodies in the cytoplasm and dense bands along the inner face of the cell membrane. Dense bodies and bands are linked by bundles of intermediate filaments composed mainly of the proteins desmin and vimentin to form the cytoskeleton, an internal scaffold giving the cell its shape. The free ends of the actin filaments interdigitate with myosin filaments. The myosin crossbridges are structured so that the actin filaments on either side of a myosin filament are pulled in opposite directions during crossbridge cycling. This draws the dense bodies towards each other, causing the cytoskeleton, and therefore the cell, to shorten. The dense bands are attached to the ECM by membrane‐spanning proteins called integrins, allowing force development to be distributed throughout the vascular wall. The interaction between the ECM and integrins is a dynamic process which is affected by forces exerted on the matrix by the pressure inside the vessel. This allows the integrins, which are signalling molecules capable of influencing both cytoskeletal structure and signal transduction, to orchestrate cellular responses to changes in pressure.
The sarcoplasmic reticulum (SR, also termed smooth endoplasmic reticulum) occupies 2–6% of cell volume. This network of tubes and flattened sacs permeates the cell and contains a high concentration (~0.5 mmol/L) of free Ca2+. Elements of the SR closely approach the cell membrane. Several types of Ca2+‐regulated ion channels and transporters are concentrated in these areas of the plasmalemma, which may have an important role in cellular excitation.
The nucleus is located in the central part of the cell. Organelles including rough endoplasmic reticulum, Golgi complex and mitochondria are mainly found in the perinuclear region.