I. General Features of the Circulatory System
The circulatory system is responsible for the transport and homeostatic distribution of oxygen, nutrients, wastes, body fluids and solutes, body heat, and immune system components.
The cardiovascular system is a closed system of tubes, through which the blood circulates with the aid of an in-line pump. It has four main components: the heart, a muscular pump; the arteries, which carry blood from the heart to the tissues; the veins, which return blood from the tissues to the heart; and the capillaries, which intervene between the arteries and veins, allowing an exchange of nutrients, oxygen, and waste products between the blood and other tissues.
The lymphatic vascular system comprises another set of vessels, in which lymph (excess tissue fluid, cellular debris, and lymphocytes) moves in only one direction (toward the junction of the lymph vessels with the large veins in the neck). This system lacks a separate pump and includes three vessel types. Lymphatic capillaries are blind-ended endothelial tubes that collect lymph from the intercellular spaces. Lymphatic vessels collect lymph from lymphatic capillaries. Lymphatic ducts collect lymph from smaller lymphatic vessels and empty into the jugular and subclavian veins.
C. Walls of Blood and Lymphatic Vessels
Circulatory system components are hollow, with an open channel, or lumen, at their center. They are described in terms of their wall structure (II). Vessel walls typically have three concentric layers or tunics. In lymphatic vessels, tunic borders are less distinct than those in blood vessels. Local weakening of vessel walls as a result of embryonic defects, disease, or lesions may cause a thin-walled outpocketing, or aneurysm, that may rupture, causing a hemorrhage.
The tunica intima is the inner layer and borders the lumen. The intima of arteries and veins and that of the heart (the endocardium) are virtually identical. It consists of endothelium (a simple squamous epithelium bordering the lumen, underlaid by a thin basal lamina) and subendothelial connective tissue. Capillaries consist solely of endothelium. In arteries, the intima is separated from the tunica media by a fenestrated layer of elastin, the internal elastic lamina.
The tunica media, or middle layer, consists mainly of circumferential vascular smooth muscle fibers. Arteries generally have a thicker media (more muscle and elastic fibers) than do veins or lymphatic vessels. Medium-sized arteries often exhibit an external elastic lamina between the media and the tunica adventitia. The heart's media (myocardium) is much thicker than that of the largest artery (aorta) and consists of cardiac muscle.
The tunica adventitia, the outermost layer, consists chiefly of type I collagen and elastic fibers that anchor the vessel in the surrounding tissues. In veins, the adventitia is the thickest layer; in large veins, it may contain longitudinal smooth muscle. In all large vessels, the adventitia contains small blood vessels (vasa vasorum) that supply oxygen and nutrients to cells in the vessel wall too far from the lumen to be nourished by diffusion. The heart's outer layer (epicardium) is not an adventitia but rather a serosa (connective tissue covered on its outer surface by a simple squamous mesothelium). The smooth surface reduces friction between the beating heart and surrounding structures.
Blood vessels are classified according to type and size. Comparisons are based on structure (Fig. 11–1) and function and often focus on the tunics’ thickness and composition (Tables 11–1 and 11–2).
These are the smallest vascular channels, with an average diameter of 7 to 9 μm. Their walls consist of a simple squamous epithelial (endothelial) cell sheet rolled into a tube and surrounded by a thin basal lamina. The cells attach to one another at their borders by junctional complexes, including tight (occluding) junctions and gap junctions. Some blood capillaries have fenestrations (pores) in their endothelial linings.
Capillary beds. The arterial tree's basic plan is such that a few large-diameter vessels branch to feed an increasing number of smaller-diameter vessels. Capillaries are the smallest vessels and hence the most numerous. They commonly occur as components of a profusion of interconnecting channels termed a capillary bed (see Fig. 11–1).
Cells of capillaries
Endothelial cells, the chief structural components of capillaries, are simple squamous epithelial cells of mesenchymal origin joined by intercellular junctions (including zonulae occludens) to form a tube. The nucleus causes each cell to bulge into the capillary lumen, but the cell thins toward its periphery to as little as 0.2 μm. Abundant pinocytotic vesicles occur throughout the cytoplasm; organelles and filaments collect near the nucleus. Key endothelial cell functions include the following: (1) producing angiotensin-converting enzyme (ACE) (mainly in the lung) to convert angiotensin I to angiotensin II (19.II.D); (2) inactivating bioactive compounds (e.g., bradykinin, serotonin, prostaglandins, norepinephrine, and thrombin) and thus regulating their effects; (3) breaking down lipoproteins (lipolysis) to yield triglycerides and cholesterol (for energy metabolism, hormone synthesis, and cell membrane assembly); (4) preventing thrombus (clot) formation (endothelial cells release prostacyclin, an inhibitor of platelet aggregation; damage to these cells may induce local clotting by decreasing prostacyclin release and uncovering the basal lamina, whose collagen stimulates thrombogenesis); (5) participating in capillary transport (II.A.4); and (6) participating in angiogenesis (II.A.5).
Pericytes, or adventitial cells, are small mesenchymal cells scattered along capillaries. Each is surrounded by its own basal lamina and clings by long cytoplasmic processes to capillary surfaces. These mesenchymal stem cells may be contractile and may differentiate into a variety of cell types.
Types of capillaries. Capillaries, like all vessels, are classified by wall structure.
Continuous capillaries have a smooth, nonporous, endothelial lining. The cells attach tightly by junctional complexes. Continuous capillaries occur in muscles, brain, and peripheral nerves.
Fenestrated capillaries have endothelial cells perforated by pores (fenestrae). The pores may be open or covered by thin diaphragms that limit the size of macromolecules able to pass. Fenestrated capillaries occur in tissues where a rapid exchange between the tissues and blood is required. Fenestrated capillaries occur in the kidneys, intestines, and endocrine glands.
Sinusoidal capillaries (1) have unusually wide lumens (30–40 μm); (2) follow a tortuous path; (3) have gaps between their endothelial cells, often allowing cells to pass; (4) have many fenestrations; (5) often have phagocytes interspersed among their endothelial cells; and (6) have discontinuous basal laminae.
Transport across capillary walls. Capillaries are exchange vessels because capillary beds serve as sites for the exchange of oxygen, nutrients, and many other substances between blood and tissues. Structural bases exist for at least four types of transcapillary transport. Fenestrae penetrate the endothelium, facilitating passive diffusion. Intercellular clefts are spaces between neighboring endothelial cells, especially in sinusoidal and lymphatic capillaries, through which particles and even cells may pass. Pinocytosis is the process by which small amounts of plasma or tissue fluid are endocytosed by endothelial cells. This mechanism is followed by the transport of membrane-bound pinocytotic vesicles across the endothelial cytoplasm in either direction. Diapedesis is the process by which leukocytes pass from blood into tissues. It involves the opening of junctions between endothelial cells by means of locally released substances (e.g., histamine, which is involved in inflammation and increases vascular permeability).
Angiogenesis is the term applied to the sprouting of new vessels from existing vessels. It involves localized activation of endothelial cells to produce matrix metalloproteases (MMPs) and other enzymes, which degrade the underlying basal lamina and create a gap. Activation also stimulates the proliferation of endothelial cells in the region, which then migrate into the gap to form a solid model of the developing sprout. Finally these cells rearrange to form the walls and a lumen in the growing sprout. Sprout elongation continues following this basic mechanism. Many growth factors are known to have a role in activating angiogenesis. The best studied of these are vascular endothelial growth factor (VEGF) and fibroblast growth factors (FGFs). Tissue hypoxia is also known to stimulate angiogenesis, in part through the expression of hypoxia inducible factor (HIF) in the endothelial cells. Well-studied inhibitors of angiogenesis include angiostatin, endostatin, and tissue inhibitors of metalloproteases (TIMPs), which inhibit the action of MMPs. Normal angiogenesis supports wound healing and tissue regeneration after trauma that disrupts or destroys a tissue's blood supply. In such cases, therapeutic enhancement of angiogenesis may enhance healing. Rapidly growing tumors deplete the available oxygen and also release growth factors that stimulate angiogenesis. The new vessels further support tumor growth and metastasis. In these cases, targeted inhibition of angiogenesis may prove therapeutic in slowing or stopping tumor growth by depriving the tumor of its blood supply.
Arteries have a thicker tunica media than do veins. The media is best exemplified in medium-sized (muscular) arteries. Large (elastic) arteries contain more elastin in their media and adventitia than any other vessels. Arteries are also distinguished by refractile, eosinophilic internal and external elastic laminae. In most sites, veins accompany arteries. In cross-sections through paired vessels, arteries appear rounder than veins, with thicker walls and smaller lumens. For more details, see Table 11–1.
In cross-sections, veins often appear collapsed. They have thinner walls than arteries and may contain more erythrocytes in sectioned tissue. They have a thicker adventitia, which in larger veins may contain longitudinal smooth muscle. Veins contain valves that help maintain unidirectional blood flow. These extensions of the intima into the lumen consist of a fibroelastic connective tissue core covered on both sides by endothelium. Blood pressure is low in veins. Valves help ensure return of blood to the heart and help prevent blood pooling. Pooling (stasis) can lead to clot formation and obstruct blood flow. For more details, see Table 11–2.
Portal vessels carry blood from one capillary (or sinusoidal) bed to another without first returning it to the heart. Examples include the hepatic portal vein between the intestines and the liver, the hypophyseal portal veins in the pituitary, and the efferent arterioles of the renal cortex.
E. Carotid and Aortic Bodies
These unencapsulated chemoreceptors comprise clumps and cords of epithelioid cells permeated by fenestrated and sinusoidal capillaries. Carotid bodies lie at the bifurcation of the common carotid artery. The left aortic body is in the wall of the aorta, near the origin of the subclavian artery. The right aortic body is in the angle between the common carotid and subclavian arteries. Changes in blood oxygen, CO2, or pH levels generate nerve impulses in their rich supply of unmyelinated nerve endings. The glossopharyngeal nerve transmits these signals to the brain, where they elicit responses that maintain homeostasis.
This unencapsulated mechanoreceptor at the bifurcation of the common carotid consists of a dilation of the arterial lumen (sinus) and a thinned media, whose outer portion contains many large nerve endings. The sinus is a baroreceptor, responding to increased blood pressure by generating impulses that are carried by the glossopharyngeal nerve to the brain, where they elicit peripheral vasodilation and reflexive slowing of the heart.
G. Arteriovenous Anastomoses
These direct connections between arteries and veins regulate blood flow by smooth muscle contraction. When they are open, more blood passes directly from arteries to veins, bypassing the capillary bed. Complex anastomoses between arterioles and venules, called glomera, occur mainly in the finger pads, nail beds, and ears. The arterioles of glomera lack an internal elastic lamina and have more smooth muscle in their media, which can contract to completely or partially close the vessels. Arteriovenous (AV) anastomoses permit efficient management of blood distribution during stress, heavy exertion, and temperature changes. They also help regulate blood pressure and other physiologic processes, such as erection and menstruation. The precapillary sphincters of metarterioles (branches of the smallest arterioles that feed capillaries) regulate the amount of blood flowing through the AV anastomoses versus the capillary beds. When the sphincters are closed, blood is shunted through the AV anastomosis. When they are open, more blood flows into the capillary bed.
H. Blood and Nerve Supply to Blood Vessels
Oxygen, nutrients, and wastes are not able to reach all cells in the walls of large arteries and veins by simple diffusion from the lumen. The vasa vasorum (“vessels of the vessels”) form a capillary network to distribute blood to cells in the vessel walls. All blood vessel walls except capillaries and some venules contain a rich nerve supply. Unmyelinated vasomotor fibers (sympathetic fibers) arise in the sympathetic ganglia, ramify in the adventitia, and terminate in small knoblike endings in the media. Arteries usually contain more of these fibers, which stimulate smooth muscle contraction. Small intra-adventitial ganglia occur in the aorta and in some other large arteries. Myelinated fibers occur in bundles in the adventitia. Their unmyelinated (free) nerve endings appear to be sensory. Many terminate in the adventitia; some extend to the intima.
Simplified schematic diagram of the vessels of the blood vascular system. Schematic cross-sections of the various types of vessels are also shown. Compare the relative thickness of the three tunics in the cross-sections: intima (light gray), media (medium color), and adventitia (light color).
Table 11–1. Comparison and Classification of Arteries. ||Download (.pdf)
Table 11–1. Comparison and Classification of Arteries.
Type, Functions, and Examples
Elastic, large, or conducting arteries: largest-diameter arteries in the body (e.g., aorta); conduct blood away from heart; help maintain constant arterial pressure; when heart's left ventricle contracts (systole), blood is expelled into aorta under high hydrostatic pressure, causing elastic arteries to stretch; as ventricle relaxes (diastole), ventricular pressure drops and elastic walls of large arteries contract, converting force that expanded them back to hydrostatic pressure
Thicker than in muscular arteries; endothelial cells of all vessels larger than capillaries contain rodlike Weibel-Palade granules that store components of factor VIII; endothelium rests on thin basal lamina, underlain by thick subendothelial connective tissue; a porous internal elastic lamina may lie between intima and media, but is hard to distinguish owing to abundant elastin in media
Contains abundant elastin as concentric, fenestrated membranes that increase in number with age; several circular layers of smooth muscle fibers lie between elastic membranes; muscle cells are interwoven with reticular (type III collagen) fibers and immersed in sparse chondroitin sulfate ground substance
Thin relative to vessel diameter; contains elastic and type I collagen fibers and external elastic lamina that may be hard to distinguish
Muscular, medium-sized, or distributing arteries: variable diameter; occur in many tissues and organs as distributing branches of elastic arteries; examples found in limbs and abdominal cavity
Contains typical endothelium and subendothelial connective tissue; prominent internal elastic lamina appears as wavy, refractile line between intima and media
Thick (up to 40 smooth muscle layers); collagen, elastic fiber, and proteoglycan amounts vary (larger arteries contain more elastin in media)
Relatively thin, contains mostly collagen fibers
Arterioles: small arterial vessels, 0.5 mm or less in diameter
Typical endothelium; often lacks subendothelial connective tissue and internal elastic lamina
One to five layers of smooth muscle encircling vascular lumen
Very thin, composed of collagen fibers
Metarterioles: branches of arterioles; constriction restricts blood flow to capillaries; precapillary sphincters, smooth muscle rings around metarterioles at capillary origins, slow capillary flow
Typical endothelium; no subendothelial connective tissue or internal elastic lamina
Incomplete single layer of smooth muscle
Table 11–2. Comparison and Classification of Veins. ||Download (.pdf)
Table 11–2. Comparison and Classification of Veins.
Type, Functions, and Examples
Large veins: largest-diameter veins (e.g., superior and inferior venae cavae); conduct blood toward heart
Well developed, includes thick subendothelial connective tissue layer
Contains several layers of smooth muscle cells and abundant reticular and collagen fibers; elastin is sparse
Best-developed layer in large veins; abundant collagen and longitudinal bundles of smooth muscle strengthen vessel wall to prevent excessive distention
Small and medium-sized veins: narrower than large veins, thinner walls; examples—saphenous (leg), hepatic portal (abdominal cavity)
Typical endothelium; less subendothelial tissue extensions of intima protrude into lumens as valves; no internal elastic lamina
Thin relative to vessel diameter; few elastic fibers
Relatively thick, but unlike large veins contains little if any muscle; contains mostly collagen
Venules: small version of vein morphology; postcapillary venules receive blood that leaves the capillaries
Contains typical endothelium, but lacks valves
Very thin; mostly collagen
The heart has four chambers: two atria, thinner-walled chambers located at the base (top) of the heart, which collect returning blood, and two ventricles, thicker-walled chambers located in the body and apex of the heart, whose forceful contractions redistribute the collected blood. See the next section (IV) for a description of the route of blood through these chambers.
The walls of the heart have three layers or tunics.
The endocardium (inner layer) is homologous to the intima of vessels and has three major components. The innermost layer is the endothelium, which is underlain by a thin, continuous basal lamina. Surrounding this is a layer of subendothelial connective tissue with elastic fibers and some smooth muscle. The subendocardium is a layer of areolar tissue with small blood vessels, nerves, and, in the ventricles, branches of the impulse-conducting system (bundle branches and Purkinje fibers; III.E.1–5).
The myocardium is the middle layer. It consists mainly of cardiac muscle fibers and carries out the forceful contractions that allow the heart to serve as a pump. It is homologous to the thinner media of vessels. It contains the impulse-conducting system and parts of the cardiac skeleton (III.C). Each cardiac muscle fiber is surrounded by an endomysium, and each fascicle of fibers is surrounded by perimysium. The muscles in the atria and ventricles differ in some important respects.
Atrial cardiac muscle is arranged in overlapping networks (musculi pectinati), giving the atria's inner surface a woven appearance. Cells in the outer myocardium form a complex helical pattern around the chamber, resembling the arrangement in the ventricles. Collagen and elastic fibers are interspersed among the muscle cells. Compared to ventricular cardiac muscle, atrial cells (1) are smaller, (2) have many granules containing atrial natriuretic factor, (3) have a less extensive T tubule system, (4) have more gap junctions, (5) conduct impulses faster, and (6) contract more rhythmically.
Ventricular cardiac muscle comprises complex cells layers wound helically around the ventricular cavity. This aids in “wringing out” the heart during contraction, maximizing the percentage of blood in the cavity expelled during contraction (ejection fraction). Superficial muscle layers surround both ventricles, whereas the deeper layers surround each ventricle individually and contribute to the interventricular septum. The inner and outer layer cells also differ in their metabolic activity. Elastic connective tissue is less abundant in ventricular than in atrial myocardium.
The epicardium, or visceral pericardium, is the outermost tunic. Although it occupies the same position as the tunica adventitia, it is a serosa rather than an adventitia. It consists of a single layer of squamous mesothelial cells, a thin basal lamina, and a layer of subepicardial areolar connective tissue that binds the epicardium to the myocardium. The smooth mesothelial surface reduces friction between the heart and the surrounding structures during contraction.
The dense connective tissue scaffolding into which the cardiac muscle fibers insert and from which the cardiac valves extend is the heart's cardiac, or fibrous, skeleton. It has three major groups of components. The annuli fibrosae are dense connective tissue rings that surround and reinforce the valve openings in the atrioventricular canals and at the origins of the aorta and pulmonary artery. The trigona fibrosae are two triangular dense connective tissue masses, occasionally containing cartilage, lying between the two groups of annuli fibrosae. The septum membranaceum is a dense fibrous plate forming the top of the otherwise muscular interventricular septum. Along with the muscle fiber arrangement, the fibrous skeleton directs the force of myocardial contraction so that the heart wrings the blood from its chambers. Parts of the skeleton may calcify during disease and aging.
These control the direction of blood flow through the heart. Each is a fold of endocardium enclosing a platelike core of dense connective tissue anchored in, and continuous with, the annuli fibrosae. The tricuspid valve, between the right atrium and ventricle, has three cusps (flaps). The free edge of each is anchored to papillary muscles in the floor of each ventricle by fibrous cords called chordae tendineae. The bicuspid, or mitral valve, between the left atrium and ventricle, has two cusps, each anchored by chordae tendineae to papillary muscles in the ventricle floor. The semilunar valves, each composed of three cusps, are not attached by chordae tendineae. Each has a characteristic thickening (nodule) at the center of its free edge. The semilunar valves are the aortic valve, between the left ventricle and aorta, and the pulmonary valve, between the right ventricle and pulmonary artery.
E. Impulse-Generating and Impulse-Conducting System
This system comprises unusual cardiac muscle cells specialized to initiate and conduct electrochemical impulses. The distribution of these cells allows the impulses they carry to coordinate myocardial contraction.
The sinoatrial (SA) node, or pacemaker node, is a small cell mass in the right atrium's median wall, near the opening of the superior vena cava. All cardiac muscle cells contract spontaneously; those with the fastest intrinsic rhythm lead neighboring cells to contract faster. Because the SA node's cells have the fastest intrinsic rhythm, they set the pace for the rest of the heart. Autonomic nerve fibers and ganglia near the SA node do not directly dictate heart rhythm but modulate heart rate. Impulses generated in the SA node travel slowly through ordinary atrial cardiac muscle to the atrioventricular node. This slow conduction allows the atria to complete their contraction before the ventricles begin theirs.
The atrioventricular (AV) node is a cell cluster on the right side of the interatrial septum. As impulses leave the AV node, they pass rapidly along the atrioventricular bundle.
The AV bundle (of His) is a bundle of specialized cardiac muscle fibers, 15-mm long and 2- to 3-mm wide, passing from the interatrial septum into the interventricular septum. It gives off a smaller bundle branch to each ventricle.
The right and left bundle branches travel a short distance before branching to form Purkinje fibers.
Purkinje fibers are cardiac muscle cells specialized to conduct electrochemical impulses. They are wider than typical cardiac muscle cells, with sparse myofilaments concentrated at the cell periphery. They are wider than bundle branch cells and, like typical cardiac muscle cells, connect by intercalated disks and have one or two central nuclei. Impulses pass through gap junctions between the Purkinje fibers and the cardiac muscle cells they contact.
Ventricular cardiac muscle cells are the last link in the impulse conduction chain. They not only contract in response to the impulse, but propagate (albeit more slowly) the impulses they receive from Purkinje fibers to their neighbors. Thus, the cardiac musculature functions as a syncytium, its cells contracting as one in a synchronous, coordinated manner.
F. Blood Supply to the Heart
The coronary arteries arise near the aorta's origin and supply oxygen-rich blood to the myocardium. Blockage of a coronary vessel or its branches by a thrombus or atherosclerotic plaque (fatty deposit in the media and intima) deprives the tissue supplied by the vessel of oxygen and nutrients. This ischemia leads to localized tissue necrosis or infarction. Tissues with high energy and oxygen demands, like the brain and myocardium, are particularly susceptible to infarction. The capillary density in cardiac muscle is greater than in skeletal muscle and is a diagnostic feature of this tissue in histologic section. Most of the venous blood returns through the coronary sinus to the superior vena cava as it enters the heart.
G. Lymphatics of the Heart
The myocardium contains abundant lymphatic capillaries that begin as blind-ended tubes near the endocardium and drain into larger lymphatic vessels in the epicardial connective tissue.
H. Innervation of the Heart
Many myelinated and unmyelinated autonomic motor fibers (sympathetic and parasympathetic) enter the heart's base (top) and ramify, forming plexuses and innervating several ganglia. There are no motor end plates in the heart. The ANS adjusts the heart rate to meet changing demands by various organs and tissues. Generally, sympathetic stimulation increases and parasympathetic stimulation decreases the heart rate.
Venous blood returns to the heart through the superior and inferior venae cavae. It enters the right atrium, which contracts and forces blood through the tricuspid valve to the right ventricle. Contraction of the right ventricle forces blood through the pulmonary (semilunar) valve into the pulmonary artery, through which it reaches the capillaries surrounding the lungs’ alveoli. Here, the blood picks up oxygen and releases carbon dioxide and other volatile wastes. Newly oxygenated blood is collected in the pulmonary veins and carried to the left atrium, which contracts to force it through the bicuspid (mitral) valve into the left ventricle. The left ventricle subsequently contracts, forcing blood through the aortic (semilunar) valve into the aorta for distribution to the body. The aorta's numerous branches distribute blood to arteries of successively smaller diameters (muscular arteries, arterioles) until it reaches the capillary beds, where it releases its oxygen and nutrients to the tissues and picks up carbon dioxide and other metabolic by-products. Some fluid escapes from the capillaries into intercellular tissue spaces; most of which returns to the capillary lumen before the blood leaves the tissue. The blood in the capillary bed enters the venules and subsequently enters veins of increasing diameters (medium-sized veins, large veins), finally returning to the heart through the largest veins, the superior and inferior venae cavae.
A. Lymphatic Vessels and Ducts
The walls of these vessels and ducts resemble those of veins. The beaded appearance of lymphatic ducts and vessels reflects the presence of valves that control the direction of lymph flow. The adventitia is thin and lacks smooth muscle. The media contains both longitudinal and circular smooth muscle, but longitudinal fibers predominate.
Like blood capillaries, these are simple squamous endothelial tubes. Unlike blood capillaries, they have a greater diameter (as wide as 100 μm) and a thinner discontinuous basal lamina. They lack fenestrations and have fewer tight junctions than blood capillaries.
The route of the lymph is unidirectional. Excess tissue fluid is collected by blind-ended lymphatic capillaries in the region of the blood capillary beds and carried through lymphatic vessels to lymphatic ducts. There is one major lymphatic duct on each side of the body: the thoracic duct on the left and the right lymphatic duct on the right. The lymphatic ducts deliver lymph to the venous system at the junction of the jugular and subclavian veins in the neck. The lymphatic system is discussed further in Chapter 14.