Neurobiology 104 – 2003 Dr Geoff Meyer

The Cardiovascular System

The cardiovascular system consists of the blood and lymphatic vascular systems, and is composed of:

The heart--whose function is to pump blood.

Arteries--whose function is to carry the blood, with nutrients and oxygen, to the tissues.

Capillaries--through whose walls the interchange between blood and tissue takes place.

Veins--whose function is to carry the products of metabolism to the heart.

Lymphatic vessels--whose function is to return fluid which has leaked into the tissue spaces, to the blood.

By distributing hormones, nutrients and oxygen to the cells and tissues of the body, and transporting waste products to the excretory organs, the circulatory system contributes to the integrated functioning of the organism.

The Heart.

The heart is a muscular organ that contracts rhythmically, pumping the blood through the circulatory system. It contains four chambers (two atria and two ventricles) through which blood is pumped. Valves guard the exits of the chambers, preventing the backflow of blood. Septae separate the left and right halves of the heart. The atria receive blood from the body or lungs, while the ventricles pump blood to the body or lungs. For this reason the ventricles are much bigger, and contain more cardiac muscle than the atria. The walls of the heart consist of three tunics: the internal or endocardium ; the middle or myocardium; and the external or epicardium.

Tunics: The endocardium is analogous to the intima of blood vessels. It consists of a single layer of squamous endothelial cells resting on a thin subendothelial layer of loose connective tissue that contains elastic and collagen fibers, as well as some smooth muscle cells. Between the endocardium and the myocardium is a layer of connective tissue which consists of nerves, veins and Purkinje cells.

The myocardium is the thickest of the tunics of the heart and consists of cardiac muscle cells arranged in layers that surround the chambers in a complex spiral. A large number of these layers insert into the fibrous skeleton.

The epicardium consists of a layer of mesothelial cells on the outer surface of the heart and some underlying connective tissue. The blood vessels and nerves that supply the heart lie in the epicardium and are surrounded by adipose tissue that cushions the heart in the pericardial cavity.

Fibrous skeleton. The fibrous skeleton of the heart is composed of dense connective tissue. It serves as the site of attachment of the cardiac valves, as well as the site of insertion of the cardiac muscle cells.

Valves. The cardiac valves consist of a central core of dense fibrous connective tissue, containing both collagen and elastic fibers, lined on both sides by endothelial layers. The bases of the valves are attached to the fibrous skeleton.

Regulation of Heart Rate.

Cardiac muscle is capable of contracting in a rhythmic manner without any direct stimulus from the nervous system. The pace of this beating action is initiated at the sinoatrial (SA) node , a group of specialized cardiac muscle cells. Because of this function, the SA node is referred to as the pacemaker. The SA node initiates an impulse that spreads along the cardiac muscle fibers of the atria, through the atrioventricular (A-V) node to the ventricles. Specialized cardiac muscle cells, Purkinje cells form Purkinje fibers, which play an important role in impulse conduction. The contraction is initiated in the atria, forcing blood into the ventricles. Then a wave of contraction in the ventricles begins at the apex of the heart, forcing blood from the heart through the aorta and pulmonary trunk.

Both the sympathetic and parasympathetic divisions of the autonomic nervous system contribute to the innervation of the heart. Although these nerves do not affect generation of the heartbeat, they do affect rhythm. Stimulation of the parasympathetic system promotes a slowing of the heartbeat, while stimulation of the sympathetic system accelerates the rhythm of the pacemaker.

All blood vessels have a number of structural features in common. They are usually composed of the following layers, or tunics:

1. Tunica Intima. The intima consists of a layer of endothelial cells lining the lumen of the vessel, and lying on a basal lamina. Beneath the endothelium is the subendothelial layer, consisting of a loose connective tissue, and sometimes smooth muscle cells. In arteries, the intima is separated from the media by an internal elastic lamina, which contains fenestrae through which substances can diffuse to the underlying tissue.

2. Tunica Media. The media consists mainly of concentric layers of helically arranged smooth muscle cells, with variable amounts of elastic fibers and elastic lamellae, reticular fibers and ground substance. Smooth muscle cells synthesize this extracellular material. In larger muscular arteries, an external elastic lamina separates the media from the adventitia.

3. Tunica Adventitia. The adventitia consists of longitudinally arranged collagen and elastic fibers. The adventitial layer gradually merges with the surrounding connective tissue.

Vasa Vasorum. In large vessels, vasa vasorum (vessels of the vessels) provide metabolites to the adventitia and the media, since these layers are too thick to be nourished solely by diffusion from the lumen.

Innervation. Most blood vessels that contain smooth muscle in their walls are supplied with a profuse network of unmyelinated sympathetic nerve fibers. Discharge of norepinephrine from these nerves results in vasoconstriction.

Arteries. Arteries transport blood to tissues. They resist changes in blood pressure in their initial portions (near the heart) and regulate blood flow in their terminal portions.

Arteries are classified according to their size into large elastic arteries, muscular arteries of medium or large diameter and arterioles. In general the walls of arteries are thicker than the walls of veins of the same diameter.

(1). Large elastic arteries. These include the aorta and its large branches. These are also called conducting arteries. They contain a large amount of elastic tissue in the media. The intima consists of the endothelium and a relatively thick subendothelial layer of connective tissue. An internal elastic lamina is present, which delimits the intima from the media. The media consist of layers of concentrically arranged elastic laminae, which contain perforations to allow for diffusion. Between the elastic laminae are smooth muscle cells, reticular fibers and ground substance. The adventitia consists of dense connective tissue containing elastic and collage fibers.

(2). Muscular arteries. Most of the named arteries in the body are muscular arteries , which are also called distributing arteries. The intima is similar to that of the elastic arteries and may contain smooth muscle cells. The internal elastic lamina is prominent. The media contains layers of smooth muscle cells, which decrease in number as the size of the artery decreases. Elastic lamellae, reticular fibers and ground substance are present. An external elastic lamina is prominent in larger muscular arteries. The adventitia consists of collagen and elastic fibers and adipose cells. Lymphatics, nerves and a vasa vasorum are also found in the adventitia.

(3). Arterioles. These generally contain 1 to 3 layers of concentrically arranged smooth muscle cells in the media. It shows no external elastic lamina. The intima consists of the endothelial cells lying on a thin subendothelial layer. The adventitia is thin.

The large elastic conducting arteries serve to transport blood away from the heart. The high content of elastic laminae serve to smooth out the large fluctuations in pressure caused by the heart-beat. During ventricular contraction (systole) the elastic laminae of the conducting arteries are stretched and reduce the pressure change. During ventricular relaxation (diastole), ventricular pressure drops to a low level, but the elastic rebound of conducting arteries helps maintain arterial pressure.

The function of the muscular distributing arteries is to furnish blood to the various organs. The muscle layer in these arteries can control the flow of blood by contracting, or not contracting, in response to local chemical or neural input.

In atherosclerosis , lesions form due to focal thickening of the intima, proliferation of smooth muscle and deposition of cholesterol in smooth muscle cells. These changes may extend to the inner part of the tunica media, and the thickening may become so great as to occlude the vessel. The large elastic arteries of the heart are most prone to atherosclerosis.

Capillaries. Capillaries are composed of a single layer of endothelial cells rolled up in the form of a tube. The average diameter of capillaries is 7 to 9 mm--about the diameter of an erythrocyte. The external surfaces of these cells usually rest on a basal lamina secreted by the endothelial cells. The total length of capillaries in the body is about 96, 000 km. Endothelial cells are held together by zonula occludens junctions. Mesenchymal cells are associated with capillaries and small venules. These cells, called pericytes, have the potential to transform into other cell types, particularly into endothelial cells. Following injury, pericytes proliferate and differentiate to form new blood vessels and connective tissue cells, thus participating in the repair process. They also contain contractile proteins such as actin and myosin, suggesting that they participate in contraction.

Capillaries can be grouped into four types:

(1). Continuous capillaries, which do not have fenestrae in their walls. Such capillaries are found in all types of muscle tissue, connective tissue, exocrine glands and nervous tissue. Numerous pinocytotic vesicles are present on both surfaces of muscle capillaries, where they are responsible for the transport of molecules in both directions across the endothelial cell. Few or no pinocytotic vesicles are encountered in the continuous capillaries supplying most parts of the nervous system. Nutrients are transported across the endothelial cells by receptor-mediated processes. This feature accounts in part for the existence of the blood-brain barrier.

(2). Fenestrated capillaries, are characterized by the presence of large fenestrae (windows) in the walls of the endothelial cells. These fenestrae are 60 - 80 nm in diameter and are closed by a specialized diaphragm that is thinner than a cell membrane. A continuous basal lamina is present. Fenestrated capillaries are found in tissues where a rapid interchange of substances occurs between blood and tissue, such as the kidney, intestine and endocrine glands.

(3). Some capillaries have no diaphragm covering the openings of the fenestrae. Instead, a very thick basal lamina is present which separates the capillary lumen from specialized epithelial cells (podocytes) which cover the capillary. This type of capillary is characteristic of the glomerulus of the kidney.

(4). Discontinuous sinusoidal capillaries have greatly enlarged diameters and follow a tortuous path, which greatly slows the flow of blood. The endothelial wall is discontinuous and the endothelial cells show many fenestrations without diaphragms. Sinusoidal capillaries are found mainly in tissues where there is an interchange of blood between the sinusoid and the tissue, such as bone marrow and spleen.

Capillary blood flow. Capillaries anastomose freely, forming a rich network that interconnects the small arteries and veins. The arterioles branch into small vessels surrounded by a discontinuous layers of smooth muscle, the metarterioles. These then branch into capillaries that form a network with a large surface area, to facilitate the exchange of nutrients between the tissues and blood. There is ring of smooth muscle at the point where capillaries originate from the metarteriole. This precapillary sphincter can completely stop the flow of blood to the capillary bed. The entire capillary network does not always function simultaneously. The flow of blood can also be directed through arteriovenous anastomoses that enable the arterioles to empty directly into venules. When vessels of the arteriovenous anastomoses contract, all the blood must pass through the capillary network. When they relax, some blood flows directly to the a venule instead of circulating through the capillaries. Capillary circulation is controlled by neural and hormonal stimulation. Because of their thin walls and slow blood flow (0.3 mm/sec, vs. 320 mm/sec in the aorta), capillaries are a favorable place for the exchange of water, solutes and macromolecules between blood and tissues.

Functions of capillaries. Capillaries perform important functions: (1). they serve as a selective permeability barrier. Capillaries are the sites at which O₂, CO₂, substrates, and metabolites are transferred from blood to the tissues. Permeability of capillary walls varies with the size and charge of the permeating molecules and with the structure of the endothelial cell. Inflammation can alter the permeability of the junctions between endothelial cells, causing swelling at the site of inflammation. White blood cells exit capillaries to access the connective tissue spaces to combat infections etc. (2). Capillary endothelial cells perform important metabolic functions. They produce substances which have an effect on blood flow, and also break down substances which are produced by other cells. (3). When endothelial cells are damaged or die, the underlying connective tissue becomes a site for the formation of a blood clot (thrombus) which can grow and obstruct blood flow, a potentially life-threatening condition. When endothelial cells are present, they prevent such thrombus formation, and are thus said to exert an antithrombogenic effect.

Veins return blood to the heart, aided by the action of smooth muscle and specialized valves. They are classified according to their size as venules , or as veins of small, medium or large size.

Venules have very thin walls. The intima consists of only endothelial cells sitting on a media which contains only a few smooth muscle cells. The adventitia is thin and consists of collagen and elastic fibers.

With the exception of the main trunks, most veins are small or medium-sized. The intima usually has a thin subendothelial layer, while the media consists of small bundles of smooth muscles, reticular and elastic fibers. The adventitia consists of collagen bundles.

Small and medium veins have valves in their lumen. These are composed of elastic connective tissue and are lined on both sides by endothelium. The valves direct the flow of blood to the heart. The propulsive force of the heart is aided by contraction of the smooth muscle surrounding these veins.

Large veins have a well developed intima, with a subendothelial layer of connective tissue and some smooth muscle cells. The media is relatively thinner, with a few layers of smooth muscle cells and connective tissue. The adventitia is thick and contains longitudinal bundles of smooth muscle, collagen and elastic fibers.

Lymphatic Vascular System.

The function of the lymphatic system is to collect fluid from the tissue spaces and return it to the blood. Unlike the blood, it circulates in only one direction--toward the heart.

The lymphatic capillaries originate in the various tissues as thin, blind ended vessels that consist of a single layer of endothelium. These capillaries are held open by numerous elastic fibers, which also bind them firmly to the surrounding connective tissue. Lymphatic capillaries absorb some of the electrolytes and proteins that continuously leave the blood capillaries. Since there are no tight junctions between the endothelial cells, tissue fluid can easily enter the lymphatic system. The thin lymphatic vessels gradually converge and end up as two large trunks--the thoracic duct and the right lymphatic duct, which enter into the venous system. Interposed in the path of the lymphatic vessels are numerous lymph nodes. The larger lymphatic vessels have a structure similar to veins, with thinner walls which contain some smooth muscle bundles. They have internal valves which assure the unidirectional flow of lymph. Lymphatic circulation is aided by the contraction of the surrounding skeletal and smooth muscles.