CARDIOVASCULAR SYSTEM

The cardiovascular system consists of the heart and blood vessels. The heart is a specialized blood vessel that acts as a pump to circulate the blood. Knowledge of the structure and function of blood vessels is important in understanding vascular diseases, the leading cause of death in this country.

Blood vessels are divided into three groups: arteries, veins, and capillaries. Two other types of atypical blood vessels are sinusoidal capillaries and sinusoids. Arteries and veins are further divided, according to size, into large, medium, and small blood vessels. The vascular system is subjected to varying degrees of hydrostatic pressure, and the structure of vessels varies in an adaptive fashion. Blood vessels are thickest and their walls more complex in the immediate vicinity of the heart, where hydrostatic pressure is greatest. As blood vessels decrease in size their wall becomes thinner and less complex.

Arteries and veins of large or medium caliber have three tunics: tunica intima, tunica media, and tunica adventitia. See Figure 32 below. The tunica adventitia contains small blood vessels (vasa vasorum), which supply nutrients to tissues in the outer one-half of the wall of the blood vessel. Small nerves, representing fibers of the autonomic nervous system, are also present in the tunica adventitia and they innervate the smooth muscle of the vessel.

Figure 32: Left photo, schematic representation of the layers of a muscular artery. Taken from Stevens and Lowe, Basic Histology, p. 141, Figure 9.5a. Right photo, diagram comparing the structure of a muscular artery and an accompanying vein. Note that the three layers that comprise the wall of the vessels are the same, just found in different proportions. Taken from Junqueira and Carneiro, Basic Histology, a text and atlas, p. 227, Figure 11-18.

The terminology for small blood vessels varies greatly and is often different among anatomists, physiologists, and pathologists. In order to avoid some of the confusion, the student should use the classification given in lecture and in the laboratory outline. This may differ from that in the text, but it is in agreement with the functional aspects of the blood vessels and will be useful in physiology.

Capillaries

A capillary is a delicate tube 7-9 mm in diameter whose wall is composed primarily of endothelium and the basement membrane upon which the endothelium rests. See Figure 33 below. There is no smooth muscle in the walls of capillaries! This is a distinguishing feature that can help you differentiate capillaries from arterioles. Examine longitudinal sections and cross sections of capillaries between the cardiac muscle fibers (slide A50, Fe & Hematoxylin). Look in the white spaces between the individual fibers and notice the circular or longitudinal structures that are surrounded by a thin purple line and contain nuclei along the periphery. No blood cells are evident within these capillaries. For another example, look beneath the epithelium of the urinary bladder (slide C6, expanded, H&E). Here the capillaries are composed of highly attenuated endothelial cells that form narrow vascular channels. Also, look in the vagina in the connective tissue underneath the stratified squamous epithelium (slide C58, human, H&E), and between the pancreatic acini (slide B85, human, Masson’s trichrome). By focusing, it is possible to see the endothelial nuclei in three dimensions. Note the length, width, and thickness and that the long dimension is parallel with the axis of the vessel. In particular, the blood vessels, in the pancreas, contain vivid red blood cells within their lumen. Start with a larger vessel and work your way out into the smaller capillaries. Vessels are cut in longitudinal and cross sections.

Figure 33: Schematic diagram of a capillary. Note that the walls are comprised of a squamous epithelium sitting on a basal lamina. Taken from Junqueira and Carneiro, Basic Histology, a text and atlas, p. 216, Figure 11-2.

Capillaries may be of three types: continuous, fenestrated and discontinuous. See Figure 34 below. Capillaries with continuous endothelium are the most common type. The endothelial cells form a continuous internal lining without any intercellular or Intracytoplasmic defects. The examples of capillaries viewed above were all examples of continuous capillaries.

Figure 34: Types of capillaries. Taken from: Stevens and Lowe, Color Histology, p. 144, Figure 9.12.

Pericytes may be found in association with the endothelium of certain continuous capillaries. The pericyte when present is enclosed by a basal lamina that is continuous with the endothelium. It is a relatively unspecialized cell that is derived from the same precursor cells that form endothelial cells in new vessels and can give rise to smooth muscle cells during vessel growth.

In fenestrated capillaries (see Figure 32 above), the endothelial cells are pierced by pores (fenestrations), which, extend through its full thickness and provide channels across the capillary wall. In some fenestrations, there may be a thin non-membranous diaphragm across its opening. Examples of fenestrated capillaries can be found in the gastrointestinal mucosa, in certain endocrine glands such as the pars distalis of the hypophysis, thyroid gland, and adrenal cortex and in the renal glomeruli. Fenestrated capillaries in the GI tract and gall bladder have fewer fenestrae and a thicker wall when no absorption is taking place. Study the fenestrated capillaries in slide C76 and C77 (pituitary, human, H&E and Halmi’s stain, respectively). It will be difficult to see the fenestrations but look for the capillaries between the individual cells in the anterior pituitary. In one slide, the rbcs are staining bright pink. In the other, the rbcs are staining reddish-orange.

Discontinuous capillaries (Sinusoidal capillaries or sinusoids) are larger and more irregularly shaped than other capillaries. They are thin-walled blood vessels lined by endothelial cells and specialized phagocytic cells (Kupffer cells of the liver). The lumen is irregular in shape and 50 mm or more in diameter. The phagocytic cells belong to the reticuloendothelial system (RES) or macrophage system of the body. Unusually wide gaps are present between the endothelial cells that permit leakage of material into and out of these vessels. There may be partial or complete absence of the basal lamina underlying the endothelium. Sinusoids should be identified in spleen (slide A57, monkey, plastic, H&E), and liver (slide B73, monkey, H&E). In slide B73, the sinusoids are the white spaces located between the cords or plates of hepatocytes. They don’t contain any rbcs within their lumen. Compare to slides B72 and B75, (liver, human & fetal human, respectively, H&E), that contain rbcs (staining red) within the sinusoidal lumens.

Arterioles

Arterioles are the smallest part of the arterial tree. These vessels regulate the flow of blood into capillaries (see Figure 35 below), which in turn, drain into venules, the first component of the venous system. Histologically, the intima of an arteriole is composed of endothelial cells lying on a basement membrane. The media layer of an arteriole has either scattered smooth muscle fibers or a single complete layer of smooth muscle around the endothelial tube. The elastic tissue forms an elastic net rather than an internal elastic membrane. Reticular fibers and collagenous fibers surround individual smooth muscle fibers and condense externally to form the tunica adventitia. The diameter of an arteriole ranges from capillary size to around 20 mm, depending largely on the degree of vasoconstriction. The arteriole is sometimes called a metarteriole (smallest arterioles or pre-capillary arteriole). Identify cross sections and longitudinal sections of arterioles in the esophagus (slides B38 and B39, upper and middle esophagus, monkey and human, H&E) and ileum (slide B59, monkey, plastic, H&E). Arterioles can be distinguished from small arteries by the number of smooth muscle layers in the tunica media layer and the tunica intima of a small artery has an internal elastic membrane.

Figure 35: Microvasculature. Taken from: Stevens and Lowe, Color Histology, p. 143, Figure 9.8.

Venules

Capillaries drain into postcapillary venules, which are the smallest venules (~10 - 25mm in diameter). They resemble capillaries in structure, but contain more pericytes. Postcapillary venules drain into large collecting venules (~20-50mm in diameter). Here the pericyte layer becomes more continuous and is surrounded by collagen fibers. As the venules increase in diameter, smooth muscle cells replace the pericytes and form a layer that is 1 to 2 cells in thickness. Use the slides listed above to identify venules, the smallest of the veins. Note that one or two venules may accompany each arteriole. The lumen is usually larger and the wall is thinner in the venule than in the arteriole. The wall of the venule lacks distinct layers and is so thin that it resembles a capillary wall.

Small arteries and small veins

These are the unnamed blood vessels. The arteries possess three tunics, which vary in thickness, but there must be at least two layers of smooth muscle for it to be classified as a small artery. Intimal, medial and adventitial layers are present in veins but they are not as clearly demarcated as in arteries. The veins contain an elastic net and some smooth muscle fibers separated by connective tissue. In comparison to arteries, veins have a larger lumen and a relatively thinner wall. Therefore, they appear collapsed in histologic sections. Study and compare the structure of the small arteries and veins that are present in the esophagus (slides B38 and B39, upper and middle esophagus, monkey and human, H&E) and ileum (slide B59, monkey, plastic, H&E).

Drawing of small artery and small vein

Using slide B38, find cross sections of a small artery and vein and draw them mostly in outline but in some areas fill in details to illustrate the components of the tunics and their arrangement.

Medium arteries and medium veins

These are the named blood vessels, which are dissected in gross anatomy. Medium sized arteries are often referred to as muscular arteries because they have more smooth muscle in their tunica media than so the small and large arteries. These arteries contain a prominent internal elastic membrane that separates the endothelial lining with its basal lamina and subendothelial layer from the smooth muscle layer of the media. The tunic media consists primarily of smooth muscle cells amid collagen fibers. The smooth muscle cells are arranged in a spiral fashion such that when they contract, they assist in maintaining blood pressure. The media layer is separated from the adventitial layer by an external elastic membrane. This adventitia is relatively thick and contains collagen and elastic fibers, scattered fibroblasts and some adipose cells.

Medium-sized veins are 1-10mm in diameter and they have an endothelial layer that sits on a basement membrane. An indistinct condensation of elastic fibers that produce a thin, discontinuous internal elastic lamina is separated from the endothelial layer by a narrow zone of collagen fibers. Together these three components comprise the inner layer of a small vein. The outer layers, the tunica media and adventitia, vary considerably in thickness due to the proportions of collagen fibers, elastic fibers and smooth muscle present within them.

Study slide A88, artery, vein & nerve (femoral), monkey, (H&E). Good example of a muscular artery, companion vein and the accompanying nerve. This constitutes a neurovascular bundle.

Study slide A89, artery, vein & nerve (femoral), monkey, (Voerhoff’s). Same section as slide A88, but stained to show the distribution of elastin. Specifically notice the internal and external elastic membranes staining black in the muscular arteries. The vein, located to the left of the artery, is irregular in shape and its walls are difficult to distinguish in comparison to the artery. The profiles of nerve are located to the right and below the arteries.

Study slide A90, artery, vein & nerve (femoral), monkey, (H&E). Elastin is stained deep purple in this preparation. Although some elastin can be seen in the tunica media of the artery, the internal and external elastic membranes contain most of the elastin as is typical of muscular arteries.

Study in slide A91 (artery, cross-section, human, elastin). This is a section of a large muscular artery and a portion of accompanying vein. There are several profiles of smaller vessels, nerves and lymph nodes present as well. Compare and contrast the walls of the smaller vessels with the muscular artery and vein.

Study slide A92, coronary arteries, cross-section, pig (Trichrome). Differentiate between the three layers of the arterial wall. Collagen fibers in the tunica adventitia are staining blue-green, nuclei and smooth muscle cells are red-violet. Coronary arteries often contain an intimal layer of longitudinally oriented smooth muscle fibers.

Study slide A93, coronary artery, cross-section, chimpanzee (H&E). Coronary arteries are thick-walled; muscular arteries differing from most other muscular arteries due to the inclusion of significant quantities of longitudinally oriented smooth muscle in the tunica intima.

Large arteries

Elastic arteries have sheets of elastic tissue in their walls and are the largest diameter arteries. The largest arteries are the aorta and pulmonary arteries, which receive the main output of blood from the left ventricle of the heart and pulmonary circulation respectively. Thus they are subjected to high systolic pressures. These large vessels are also adapted to smooth out the surges in blood flow since blood only flows through them during systole. The elastic tissue in their tunic media provides the resilience to smooth out this pressure wave. The immediate branches of these arteries are also considered to be elastic arteries (brachiocephalic, common carotids, etc.).

Examine with the scanning objective the section of large elastic artery (aorta, cross-section, human, elastic) on slide A84. Note the relative thickness of the tunics. The tunica intimal is relatively thick and consists of an endothelial layer with its basal lamina, a subendothelial layer of connective tissue and an internal elastic membrane. Identify each of these layers under higher power. The internal elastic membrane is not as conspicuous because it is one of the many elastic layers in the wall of the vessel. It is usually only identified because it is the innermost of the elastic layers of the arterial wall. The tunica media is the thickest of the three layers. The numerous, thick, black-stained elastic membranes are the predominant substance of the media. They are interconnected by finer elastic fibers and also by smooth muscle, which spirals at a slight angle to the transverse axis of the vessel. The smooth muscle is surrounded by reticular fibers and a few collagenous fibers. In elastic arteries, the tunica adventitia is relatively thin – half the thickness of the media – and contains collagen fibers, elastic fibers and connective tissue cells (fibroblasts and macrophages). The tunic adventitia contains blood vessels (vasa vasorum) and nerves (nervi vascularis) that supply the blood vessel wall.

Study slide A82, aorta, longitudinal section, human, (H&E). Delineate the three layers of the arterial wall. Notice the thickness of the tunica intima and the thinness of the tunic adventitia in comparison to the tunica media.

Study slide A83, aorta, human, (Voerhoff's). Same section of tissue as seen on slide A82. The three tunics of the elastic artery are readily distinguished.

Study slide A85, aorta, cross-section, monkey, plastic, (H&E). Note the absence of a vasa vasorum in the tunica intima and tunica media.

Drawing of tunica media of elastic artery

From slide A84 (elastic, H&E), draw part of the tunica media to show several fenestrated elastic membranes, and the arrangement of other tissue components that occur between the membranes.

Large veins

Examine the section of slide A87, vena cava, cross-section, human, (elastic). Note the difference in thickness of the various tunics in comparison to the aorta. In large veins, the tunica media is relatively thin and consists of an endothelial lining with its basal lamina, a small amount of subendothelial tissue and some smooth muscle cells. Observe the thin tunica media with its sparse, circularly arranged smooth muscle. Also present are collagen fibers and some fibroblasts. The most obvious feature is the thickness of the tunica adventitia. In large veins, such as the vena cava and subclavian veins, large bundles of longitudinal disposed smooth muscle cells are found with the usual collagen and elastic fibers.

Tabulate the important identifying characteristics you can use to differentiate between the types of medium blood vessels.

HEART

The heart is a pump with four chambers and valves that maintain a one-way flow of blood. The wall of the heart includes: (1) cardiac musculature for contraction to propel the blood out of each chamber and into the major vessels, (2) a fibrous skeleton for attachment of the valves and (3) an internal conducting system for synchronization of muscle contraction.

Cardiac wall

The structure of cardiac muscle was studied earlier and should be reviewed at this time (slides A49, Trichrome and A50, Fe-Hematoxylin).

Study slide A73, heart, human, (Trichrome). Ventricular wall with myocardium and epicardium. Note the coronary vessels and nerve fibers in the pale adipose tissue comprising the epicardium. Muscle fibers stain red and collagenous fibers green.

Study slide A74, ventricle & papillary muscle, monkey, plastic (H&E). This is a thin section through the ventricular wall. Intercalated disks are well stained. Some sections will have Purkinje fibers near the inner layer (endocardium). These will be large, pale fibers with voluminous sarcoplasm and relatively few myofibrils.

Fibrous Skeleton

The fibrous skeleton is comprised of dense connective tissue that encircles the base of the two arteries leaving the heart and the openings between the chambers. It serves as an attachment for cardiac muscle and the cuspid valves of the atria and ventricles. It also serves as an attachment site for the semilunar valves of the aorta and the pulmonary artery. The atrioventricular (A-V) bundle passes from the right atrium to the ventricular septum via the fibrous skeleton. See Figure 36 below.

Figure 36: Schematic diagram of the conducting system of the heart. Taken from Junqueira and Carneiro, Basic Histology, a text and atlas, p. 228, Figure 11-20.

Study slide A78, aortic valve, human, (Trichrome). Nice profile of the valve leaflet flopped back against the aortic wall. The stain is unusual. Most fibers (myofibrils, collagen, etc.) are blue, nuclei are very pale often appearing as ghosts or negative images. Intercalated disks of ventricular myocardial cells are very prominent. RBC's are red-orange and enable

visualization of the extensive plexus of capillaries in the myocardium.

Study slide A79, aortic valve, human, (H&E). Sagittal section of aorta at the level of the aortic valve. Note the appearance of "chondroid tissue" in the cardiac skeleton at the valve base and, to a lesser extent, in the valve plate. A portion of the atrial wall is seen beneath the aorta.

Slide A80 shows the aortic semilunar valve and the AV valve, human, (Voerhoff’s). See Figure 37 and 38 below as a reference. Hint: For correct orientation, place the slide on the stage backwards to match the diagram. This is a fortunate plane of section, which includes the aorta, aortic valve, atrial wall, membranous septum, AV valve and interventricular septum. The aorta is sectioned longitudinally and stains dark black due to the elastic fibers present within it. Identify the leaflets of the valves and the annulus of dense connective tissue to which the leaflets attach. The AV valve (tricuspid) is more representative than is the short piece of aortic valve. The aggregate of modified cardiac muscle fibers beneath the fibrous annulus of the AV valve is probably part of the AV Bundle. The fibers are not yet enlarged to form Purkinje fibers. Study the basic pattern of the leaflets, noting that they are folds of endocardium reinforced with dense connective tissue that forms the central core. The endocardium facing the left ventricular chamber is better developed than that on the right and some smooth muscle can be seen within the endocardial layer. Also note the manner in which the cardiac muscle fibers take origin from the annulus. Cardiac and smooth muscle are yellowish orange and collagenous tissue (e.g., cardiac skeleton) stains red.

Figure 37: Aortic semilunar valve and the AV valve.

Figure 38: Heart Valve. E = endothelium, M = myocardium, S = fibroelastic supporting structures and F = lamina fibrosa. Taken from Wheater’s Functional Histology, a text and colour atlas, p. 146, Figure 8.5.

Purkinje Fibers

Purkinje fibers are modified cardiac muscle fibers found in the subendocardium of the ventricles. They constitute part of the specialized impulse conducting system, which connects to the right and left bundle branches and regulates the heartbeat. These are large muscular fibers with a vacuolated cytoplasm due to the high glycogen content. Other characteristics that help distinguish Purkinje fibers from typical cardiac muscle fibers are that they contain fewer myofibrils, and more sarcoplasm.

Study slide BB35, heart, Purkinje fibers, human, (H&E). Purkinje fibers of the bundle are present in the deep portion of the endocardium ("subendocardium”).

Study slide BB36, heart, moderator band, human, (H&E). This is a section of the septomarginal trabecula, a band of muscle, which carries, as Purkinje fibers, a branch from the right atrioventricular bundle. It is not a distinct structure in most hearts.

Study slide BB37, heart, Purkinje fibers, ox, (Best's Carmine). Purkinje fibers are located in the subendocardium and are intensely stained red due to the large quantity of glycogen in their sarcoplasm.

Study slides A77, heart, Purkinje fibers, (iron hematoxylin). Species of unknown origin, but probably from an ungulate (cow). Note the prominent bundles of Purkinje fibers, which in contrast with those of the human heart, are occasionally found deep in the myocardium.

Lymphatic vessels

These vessels convey fluids from the tissues to the bloodstream. They are an adjunct to the blood vessels (See top photo in Figure 39a below). However, in contrast to blood vessels, which carry blood to and from tissues, lymphatic vessels are unidirectional (See bottom photo in Figure 39b below) due to the presence of valves which direct the flow of lymph. They are also more permeable than blood vessels. The smallest lymph vessels are lymphatic capillaries. They are especially numerous in loose connective tissues of the skin and in mucous membranes. They converge into larger vessels that ultimately unite to form two main channels that empty lymph into the blood stream.

Figure 39: Lymphatic vessels. Top photo, small lymphatic vessel next to a small vein. Lymphatics due not contain RBCs, but often contain a few lymphocytes. Bottom photo, a valve present within the lymphatic vessel. Taken from Wheater’s Functional Histology, a text and colour atlas, p. 156, Figures 8.22 and 8.23.