Circulatory system

1. Circulatory system components.

2. The general features of vessel wall structure.

3. Dependence of vessels’ wall on the haemodynamic conditions.

4. Arteries classification and functional meaning.

5. Elastic, mixed and muscular arteries structure.

6. Veins, their differences compare to arteries.

7. Veins classification and functions.

8. Morphofunctional characteristic and significance of the microcirculatory bed.

9. Blood capillary wall structure. Ultrastructural peculiarities and regeneration of the endothelium.

10. Classification of the capillaries on their  endothelium and basement membrane structure.

11. Microscopic structure of the arterioles and venules.

12. Anastomoses classification, structure and functions.

13. Lymphatic system components and significance. Lymphatic capillaries.

14. Layers  of the heart wall.

15. Structure of the endocardium. Comparison with the structure of the blood vessels’ wall.

16. Myocardium: structure of cardiac muscle cells compare to the cells of conductive system.

17. Comparison of the structure of  heart valves  and  vein valves.

18. Conducting system of the heart. Structural features of the atypical cardiomyocytes  and impulse generating  mechanism.

19. Nerve regulation of the heart activity.

20. Regeneration of the heart.

 

 

Circulatory system diseases are one of the most widespread diseases in the world. Nervous stress of modern life proves that. Very often death from the heart attack affects young working men contributes very much to the reason of mortality.

The circulatory system is a special system that mediates the continuous movement of all body fluids. Its principal functions being the transport of oxygen and nutrients to the tissues and transport of carbon dioxide and other metabolic waste products from the tissues. The circulatory system is also involved in temperature regulation and the distribution of molecules such as hormones, and cells such as those of the immune system. The circulatory system has two functional components: the blood vascular system and the lymph vascular system.

The blood vascular system comprises a circuit of vessels through which flow of blood is maintained by continuous pumping of the heart. The arterial system provides a distribution network of the capillaries, which are the main sites of interchange of gases and metabolites between the tissues and blood. The venous system returns blood from the capillaries to the heart. In contrast the lymph vascular system is merely a passive drainage system for returning excess extravascular fluid (the lymph) to the blood. The lymph vascular system has no intrinsic pulping mechanism.

The whole circulatory system has a common basic structure: an inner lining comprising a single layer of extremely flattened epithelial cells, called endothelium, supported by a basement membrane and delicate loose connective tissue with collagenous fibres, constitutes the tunica Intima.

An intermediate vascular layer, the tunica Media, contains smooth muscular tissue, collagen and elastic fibers. The muscular layer exhibits the greatest variation from one part of the system to another. For example, it is totally absent in capillaries but comprises almost the whole mass of the heart. Blood flow is predominantly influenced by variation in activity of the muscular layer.

The outer supporting tissue layer, called the tunica Adventitia, is presented with loose connective tissue. While the tissues of the large vessels walls cannot be sustained by diffusion of nutrients from their lumen, thus they are supplied by small arteries called vasa vasorum (i.e. "vessels of vessels"), which are derived either from the vessel itself or from adjacent arteries. The vasa vasorum give rise to a capillary network within the tunica Adventitia that may extend into the tunica Media.

 

the blood vascular system

 

The blood vascular system includes such components as arteries, veins, microcirculatory bed and the heart.

The function of the arterial system is to distribute blood from the heart to capillary bed throughout the body. The cyclical pumping action of the heart produces a pulsative blood flow in the arterial system. With each ventricles contraction (systole), blood is forced into the arterial system causing expansion of the arterial walls subsequent recoil of the arterial walls assists. In maintenance of arterial blood pressure between ventricular beats (diastole), this expansion and recoil is a function of elastic tissue within the walls of the arteries. The flow of blood to various organs and tissues may be regulated with varying the diameter of the distributing vessels. This function is performed by the circumferentially disposed smooth muscle of vessel walls and is principally under the control of the sympathetic nervous system and adrenal medullary hormones (adrenalin and noradrenalin).

The high blood pressure and speed are the principle features (hemodynamic conditions) of the blood flow in the arteries. The walls of the arterial vessels conform to the general three-layered structure of the circulatory system but are characterised by the presence of considerable elastin and the smooth muscle wall is thick relative to the diameter of the lumen.

There are three main types of vessels in the arterial system: elastic, muscular and mixed ones due to the amount of muscular and elastic fibers in the middle tunica.

Elastic arteries (aorta and pulmonary artery) are the largest vessels in human body. Their tunica Media mainly contains the elastic fibers, which is organized in specific perforated lamina. They have a yellowish color because of accumulation of elastin.

Common carotid and subclavian arteries, for example, are of mixed type. There are “fifty-fifty” muscular and elastic fibers in their wall. All of them are middle-sized vessels.

Muscular arteries (small arteries) are the main distributing branches of the arterial tree, e.g. the radial, femoral, coronary and cerebral arteries. They contain predominantly muscular fibers in the middle tunica.

 

The general structure of the mixed artery

Mixed arteries have the most complicated structure; all the other vessels may be compared to them.

 

 

Drawing of a medium-sized muscular artery, showing its layers. Although the usual histologic preparations cause the layers to appear thicker than those shown here, the drawing is actually similar to the in vivo architecture of the vessel. At the moment of death, the artery experiences an intense contraction; consequently, the lumen is reduced, the internal elastic membrane undulates, and the muscular tunica thickens.

 

Tunica Intima of mixed artery consists of 3 layers. Endothelium (special type of simple squamous epithelium) is the first one. It lies on the basement membrane bordered with loose connective tissue of subendothelial layer.

Elastic fibers of internal elastic lamina separate tunica Intima from the tunica Media. This one is the thickest in the arteries wall and contains chiefly concentric layers of smooth muscle cells and elastic fibers (fifty-fifty). This well developed tunica proves the circular shape of the arteries in the histologic specimen.

 External elastic lamina separates the Media from the outer tunica Adventitia; it is thinner then the internal ones and has the same compounds.

Elastic arteries

 

Aorta and pulmonary artery are typical elastic vessels, whose muscular tunic mainly consists of elastic fibers.

 

 

Low power view of wall of aorta, an elastic artery:

 

 

Detail of inner portion of aortic wall: "a" bar = depth of tunica intima (next to lumen). In the media there are many layers of wavy, dark-stained elastic membranes, alternating with the paler pink smooth muscle and areolar connective tissue. (Note that these are elastic membranes, not just fibers. Think of many layers of rubber sheets enwrapping the vessel and you have cut across them and are looking at the cut edges. These sheets are fenestrated; i.e., they have holes in them, thus allowing passage of nutrients diffusing from the blood in the aortic lumen out into the tissues of the wall). Arrows = nuclei of smooth muscle cells.

 

The highly elastic nature of the aortic wall may be demonstrated in the specimens in whom the elastic fibres are stained brown with orsein. The three basic tunices of the wall can be seen: the tunica Intima well developed tunica Media and the tunica Adventitia. The tunica Intima consists of a single layer of flattened endothelial cells supported by a layer of collagenous tissue rich in elastin disposed in the form of both fibres and dicontinuous sheets. The subendothelial supporting tissue contains scattered fibroblasts and other cells with ultrastructural features like in smooth muscle cells and known as myointimal cells. Both cell types are probably involved in elaboration of the extracellular constituents. The myointimal cells are not invested by basement membrane and are thus not of epithelial (myoepithelial) origin. With age, the myointimal cells accumulate lipid and the Intima progressively thickens: in a more extreme form this represents one of the early changes of arteriosclerosis. The tunica Media is particularly broad and extremely elastic. At high magnification, it is seen to consist of concentric fenestrated sheets of elastin separated by collagenous tissue and relatively few smooth muscle fibres. The collagenous tunica Adventitia consists of loose connective tissue with collagen and elastic fibers, smooth myocytes, vessels (vasa vasorum) and nerves. Small vasa vasorum also penetrate the outer half of the tunica Media.

 

 

          Detail of outer portion of aortic wall, showing blood vessels (vasa vasorum) in the adventitia. These vessels bring nutrients only to the outer one-third or so of the vessel wall.

 

Blood flow within elastic arteries is highly pulsative: with advacing age the arterial system becomes less elastic thereby peripheral resistance increases and thus arterial blood pressure increases too.

 

Muscular arteries

 

          Muscular arteries Intima is similar to that of mixed arteries except of subendothelial layer is somewhat thinner and a few smooth muscle cells may be present. The Intima often is so thin as to be indistiguishable at low magnification. The Media has the same basic structure as in elastic arteries but the elastic tissue is reduced to a well-defined, fenestrated elastic sheet, the intetrnal elastic lamina, separating the tunica Intima from the tunica Media, and a less defined external elastic lamina at the junction of the Media and the tunica Adventitia. Sometimes the internal elastic lamina is diplicated. The tunica Media comprises a thick layer of circumferentially arranged smooth muscle. It may contain up to 40 layers of smooth muscle cells, although the number of layers diminishes as the artery becomes smaller.

The broad tunica Adventitia is mainly composed of collagen with considerable elastin, a few fibroblasts and adipose cells. Lymphatic capillaries, vasa vasorum, and nerves are also found in the Adventitia, and these structures may penetrate to the outer part of the Media.

 

Diagrams of a muscular artery prepared by H&E staining (left) and an elastic artery stained by Weigert’s method (right). The tunica media of a muscular artery contains predominantly smooth muscle, whereas the tunica media of an elastic artery is formed by layers of smooth muscle intercalated by elastic laminas. The adventitia and the outer part of the media have small blood vessels (vasa vasorum) and elastic and collagenous fibers.

 

 

          A medium-sized (muscular) artery, showing the typical 3 wall layers:

 

 

          Cross sections of small arteries. A: The elastic lamina is not stained and is seen as a pallid lamina of scalloped appearance just below the endothelium (arrowhead). Medium magnification. B: A small artery with a distinctly stained internal elastic lamina (arrowhead).  Gomori stain. Low magnification.

 

 

          A small artery cut longitudinally. Notice the circular arrangement of smooth muscle cells cut tangentially at the left end. For most of the vessel, the muscle is cross-cut, looking almost like an epithelium. The real epithelium, however, is the simple squamous endothelium immediately lining the lumen, with thin, flat nuclei oriented longitudinally along the vessel.

 

          Another medium-sized, muscular artery (also called a distributing artery). This is typical of the arteries you dissected in the arm; it usually runs with a vein and nerve. There is a characteristic inner elastic membrane (dark pink with arrow pointing to it) and a heavy circular muscle in tunica media. Note that a = adventitia.

 

 

EM photo of inner elastic membrane (white band). Endothelial cells are bunched up because the wall is contracted.

 

The microcirculatory bed

 

The microcirculation is that part of the citculatory system concerned with the exchange of gases, fluids, nutrients and metabolic waste products. In different tissues, the structure of the rnicroclrculation varies to meet specific functional requirements. The principle components of microcirculatory bed are: arterioles, capillaries, venules and anastomoses.

Microcirculatory bed performs next functions: blood distribution and regulation of blood supply, gases and   matters exchanges,  blood deposition and barriers between blood and tissues.

 

Arterioles are the terminal branches of the arterial tree, which supply the capillary beds. There is a gradual transition in structure and function between the three types of arterial vessel rather than an abrupt demarcation. At all, the amount of elastic tissue decreases as the vessels become smaller and the smooth muscle component assumes relatively greater prominence.

 

          Cross section of 2 venules and 4 small arterioles. The walls of the arteries are thicker than the walls of the veins. A lymphatic vessel can be seen at the top. Note the cross sections of smooth muscle cells and the field of loose connective tissue that surrounds the vessels. Toluidine blue stain. Medium magnification.

 

Arterioles may be defined as those vessels of the arterial system with a lumen less than 0,3 mm in diameter, although the distraction between small muscular arteries and large arterioles is somewhat artificial. The tunica Intima is very thin and comprises the endothelial lining, a little collagen supporting tissue and a thin internal elastic lamina. The tunica Media is almost entirely composed of smooth muscle cells in six concentric layers or less. The tunica Adventitia may be almost as thick as the tunica Media and merges with the surrounding collagen tissues. There is no external elastic lamina in such vessels.

 

 

The smallest arterioles have a single layer of smooth muscle outside the endothelium, and a lumen hardly wider than a capillary. Toward the upper center of this field is a round, cross-cut arteriole with just one or two layers of muscle in the media. To the right is the more irregular, wider shape of a venule with only a thin adventitial wall.

The flow of blood through capillary beds is regulated mainly by the small arteries, which supply them. Contraction of the circularly arranged smooth muscle cells of their wall reduces the diameter of the lumen and hence blood flow. Generalized constriction of small arteries throughout the body markedly increases peripheral resistance to blood flow and this compartment of the circulatory system thus has an important role in the regulation of systemic blood pressure.

Exchange occurs mainly within the capillaries, extremely thin walled vessels, forming an interconnected network. Within the capillary bed blood flow is controlled with the muscular sphincters of the small arteries. The capillaries drain into a series of vessels of increasing diameter namely post-capillary venules, collecting venules and small muscular venules that make up the venous component of the microcirculation.

 

Three-dimensional representation of the structure of a capillary with fenestrae in its wall. The transverse section shows that, in this example, the capillary wall is formed by 2 endothelial cells. Note the basal lamina surrounding endothelial cells.

 

 

 

 

There are three types of capillaries: continuous, fenestrated and sinusoids due to their size and structure of basement membrane and endothelium. Diameter varies between as little as 3 to 4 ìm (half diameter of a red blood cell) and 30 to 40 ìm.

The principal differences may be observed first of all in the nature of the capillary endothelium and basement membrane.

 

EM of different capillary endothelia.

Note: basal lamina (1) under each one. Also pinocytotic vesicles (PV) and fenestrations (arrows).

 

A single layer of flattened endothelial cells lines the capillary lumen. The thin layer of cytoplasm is difficult to resolve by light microscopy. The flattened endothelial cell nuclei bulge into the capillary lumen in longitudinal section the nuclei appear elongated, whereas in transverse section they appear more rounded in shape. Near this nuclear zone of the endothelial cell different organelles (Golgi apparatus, mitochondria, endoplasmic reticulum, ribosomes) may be observed in so called “organelles zone”. Peripheral part of the cell is the thinnest and has no organelles, there may be a lot of vesicles, which are the evidence of transcellular transport. Each endothelial cell has two surfaces: the first one lies over the basement membrane is termed “basal surface” the opposite one – luminal surface may have some processes “microvilli”, which are the evidences of cell activity.

 

 

                Endothelium (simple squamous epithelium) lines the lumen of all blood and lymph vessels, as well as the heart. Here flat endothelial nuclei are seen ringing a venules with erythrocytes inside. Venule is identified because its wall consists of endothelial layer and a thin coat of connective tissue outside it, the lumen of this vessel is too large to be a capillary, and it can’t be sinusoid because they don't occur in ordinary connective tissue areas like this.

 

 

 

A capillary lying in the endomysium between skeletal muscle fibers. This one shows very dark endothelial nuclei and has 3 pink r.b.c.'s lined up in a row inside.

 

Muscular and adventitial layers are absent, occasional flattened cells called pericytes embrace the capillary endothelial cells and may have a contractile function. Note  that the diameter of capillaries is similar to that of the red blood cells contained within them.

Next scheme illustrates the ultrastructure of capillaries of the continuous endothelium type, the type found in most tissues. Capillary of this type has nonfenestrated endothelium and continuous basement membrane. Endothelial cells are seen to encircle the capillary lumen, their plasma membranes approximating one another very closely and bound together by scattered tight junctions of the fascia occludens type. Small cytoplasmic flaps called marginal folds extend across the intercellular junctions at the luminal surface.

The capillary endothelium is supported by a thin basement membrane and adjacent collagen fibrils. A pericyte embraces the capillary. They are disposed in the basement membrane inside. In the adjacent supporting tissue, note a fibroblast and larger diameter collagen fibrils cut in transverse and longitudinal section.

 

Exchange between the lumen of the continuous type capillary and the surrounding tissues is believered to occur in three ways. Passive diffusion through the endothelial cell cytoplasm mediates exchange of gases, ions and low molecular weight metabolites. Proteins and some lipids are transported by pinocytotic vesicles. White blood cells pass through the intercellular space between the endothelial cells in some way negotiating the endothelial intercellular junctions. Some workers maintain that the intercellular spaces also permit molecular transport. In capillaries of the continuous endothelial type, the basement membrane and surrounding structures are thought to present so called hysto-hematical barrier to exchange between capillaries and surrounding tissues.

Continuous (somatic) capillaries are the smallest ones and may be found in striated muscles (both skeletal and cardiac), skin, lungs, and central nervous system. The endothelial cells form a lining on the uninterrupted basement membrane. These are the most common type of capillaries.

Peripheral part of endothelial cell may have special fenestrations. At low magnification they appear as pores through attenuated areas of the endothelial cytoplasm: however, only a small proportion of these areas are fenestrated. At high magnification, the fenestrations appear to be traversed by a thin electron-dense line, which may constitute a diaphragm: the biochemical and functional nature of this is not understood. The permeability of fenestrated capillaries is much greater than that of continuous endothelium type capillaries and molecular labeling techniques have demonstrated that fenestrations permit the rapid passage of macromolecules smaller than plasma proteins from the lamina of fenestrated capillaries into surround tissues.

 

 

          Electron micrograph of a transverse section of a continuous capillary. Note the nucleus (N) and the junctions between neighboring cells (arrowheads). Numerous pinocytotic vesicles are evident (small arrows). The large arrows show large vesicles being formed by infoldings of broad sheets of the endothelial cell cytoplasm. x10,000.

 

Fenestrated capillaries are largest (10-20 ìm), their endothelial cells contain numerous large pores or fenestrations in the peripheral portion of cells which are closed with special diaphragms called fenestrae. Like continuous endothelium type capillaries, all fenestrated capillaries are supported by a basement membrane that is continuous across the fenestrations pericytes are rarely found in association with fenestrated capillaries. Such capillaries are found in some tissues where there is extensive molecular exchange with the blood; such tissues include the small intestine, endocrine glands and the kidney.

 

 

          A fenestrated capillary in the kidney. Arrows indicate fenestrae closed by diaphragms. In this cell the Golgi complex (G), nucleus (N), and centrioles (C) can be seen. Note the continuous basal lamina on the outer surface of the endothelial cell (double arrows). Medium magnification.

 

Large diameter (more then 20 ìm) capillaries are called sinusoids: these are found in the liver, spleen, lymph nodes and bone marrow. They take their name from the irregular shape of the surface. Sinusoids usually have an irregular outline, which conforms to the cellular arrangement of the tissue in which they are found. Their discontinuous endothelium: do not form a continuous interface between the lumen and surrounding tissues: this arrangement is found only within the sinusoids, and basement membrane is interrupted.

Different capillaries characteristic features

 

Capillary type

Size, d (ìm)

Endothelium

Basement membrane

Location

Continuous

< 10
Continuous
Continuous

Muscles, con-nective and nervous tissue, exocrine glands

Fenestrated

10-20

Fenestrated

Continuous

Kidney, intestine, endocrine glands

 

Sinusoidal

>> 20

Fenestrated

Discontinuous

Hematopoietic organs

 

 

 

          Diagram of routes of transport across capillary or sinusoidal endothelial cells. (Notice that we now also consider discontinuous endothelium as well as the types you saw on the previous slide.)

"Spikes" on the outer leaflet of membrane = glycocalyx layer.

 

 

This sinusoid, like a capillary, has only an endothelial wall, but its lumen is characteristically considerably wider. Also, in some locations in the body (such as bone marrow, liver, and spleen) the endothelial cells of sinusoids are rather loosely joined together, thus permitting passage of blood cells between them.

 

 

In the middle of the field is a sinusoid (filled with orange-colored r.b.c.'s) in the marrow cavity of spongy bone. (The larger empty circles are fat cells.)

 

Post-capiIIary and collecting venules. The capillary beds are drained by a series of thin-walled vessels which form the first part of the venous system, Post-capillary venules are the smallest of these vessels and are formed by the union of several capillaries to produce a vessel similar in structure but of a wider diameter. Blood flow in post-capillary venules is sluggish and these vessels appear to be the main point at which white blood cells enter and leave the circulation. Post-capillary venules drain into collecting venules, which are characterized, by their larger diameter and a greater number of enveloping pericytes. Collecting venules drain into vessels of progressively greater diameter, the walls of which contain a recognizable layer of smooth muscle and which are therefore known as muscular venules.

 

Types of microcirculation formed by small blood vessels. (1) The usual sequence of arteriole —> metarteriole —> capillary —> venule and vein. (2) An arteriovenous anastomosis. (3) An arterial portal system, as is present in the kidney glomerulus. (4) A venous portal system, as is present in the liver.

 

arterio-venous anastomoses (shunts)

 

As a rule there is a network of capillaries between the arterioles and venules, but sometimes it is necessary to pass the blood very quickly through the anastomoses. These structures of the microcirculatory bed prove direct connections between the arterial and venous systems. They have diameter at about 30-500 ìm and length 4 ìm.

AVA functions are the next:

1.     Regulation (correction) of the blood pressure.

2.     Blood supplying of organs.

3.     Venous blood saturation with oxygen.

4.     Blood withdrawing from the depot.

5.     Regulation of the tissues fluid passage to the venous bed.

The abundance of the capillary network thus depends on the functional necessities of the tissue. For example, the dense collagen tissue of tendons has a sparse capillary network; in contrast, cardiac muscle has an extensive capillary network, which pervades the interstices between the muscle fibres. The capillary network comprises small diameter capillaries, consisting of only a single layer of endothelial cells.

Due to their structure AVA may be divided into such groups: typical (proper) and nontypical. In the first ones the pure arterial blood passes to the venules. Nontypical are longer and similar to short capillary, that is why the mixed blood passes in it.

There are simple and special typical anastomoses. Blood flow in simple shunts is regulated by the contraction of middle tunic myocytes. Note that small capillaries arise from arterioles. At the origin of each capillary there is a sphincter mechanism, the precapillary sphincter, which is involved in regulation of capillary blood flow. Hole also a direct wide-diameter communication between the arteriole and venule: an arterio-venous shunt. Contraction of the smooth muscle of the shunts directs blood through the network of small capillaries, thus regulation of blood flow in the microcirculation is mediated by arterioles, precapillary sphincters and artero-venous shunts. The smooth muscle activity of these vessels is modulated by the autonomic nervous system and circulating hormones, e.g. adrenal catecholamines. In addition, the concentration of oxygen and metabolites, such as lactic acid, regulate the local flow of blood within tissues; this process is called auto regulation.

In the second group of typical anastomoses there are special myoid or epithelioid cells, which lie along the vessel. The last ones may be simple or compound due to the amount of anastomoses branches. Compound typical anastomoses contain few branches surrounded with connective tissue capsule.

 
The venous system

 

With the exception of the venous components of the microcirculation the venous system merely functions as a low pressure collecting system for the return of blood from the capillary networks to the heart.  The others functions of the veins are storage of the blood and drenage.

Blood flow in veins occurs passively down a pressure gradient towards the heart. With each inspiratory cycle, a negative pressure is created within the chest and hence within the right atrium of the heart. Venous blood return from the limbs is aided by the contraction of skeletal muscles, which compress the veins contained within them. During expiration, the pressure gradients are reversed and blood tends to flow in the opposite direction. This is prevented by the presence of valves in veins of medium size. The valves also overcome the problem of reverse flow due to the effects of gravity especially in the lower limbs. Waive failure is the basis for the development of varicose veins.

Veins are classified due to their structure into fibrous (nonmuscular) and muscular type. The last ones include the vessels with well, middle and worse developed muscular elements in the wall.

 

Medium-sized vein with a much less compact muscle layer than you saw in the preceding arteries. The tunica media is indicated by bar "a". Bar "b" = adventitia, which is at least as wide as the media, and often even wider. There is no evident inner elastic membrane. (Blood in the lumen stains red here.) To the right, compare sizes and walls of one small artery (d) and two very small veins (c) and (e).

 

 

          Cross section through a small artery and its accompanying muscular vein. Because of vasodilatation, the arteriole is unusually filled with blood. At this stage the internal elastic lamina is not distinguished. Many other small arterial branches and capillaries can be seen in the surrounding connective tissue. Pararosaniline–toluidine blue (PT) stain. Medium magnification.

 

The structure of the venous system conforms to the general three-layered arrangement elsewhere in the circulatory system, but the elastic and muscular components are much less prominent features. A major part of the total blood volume is contained within the venous system. Variations in relative blood volume, due for example to dilation of capillary beds or hemorrhage, may be compensated by changes in the capacity of the venous system. These changes are mediated by smooth muscle in the tunica Media, which controls the luminal diameter of muscular venules and veins.

 

          Diagram comparing the structure of a muscular artery (left) and accompanying vein (right). Note that the tunica intima and the tunica media are highly developed in the artery but not in the vein.

 

Muscular veins are characterized by a clearly defined intimal layer devoid of elastic fibres and a tunica Media consisting of one or two layers of smooth muscle fibers. Veins are characterized by a thicker muscular wall and a poorly developed internal elastic lamina. Note that the tunica Adventitia of these vessels is continuous with the surrounding collagenous supporting tissue. The tunica Intima consists of little more than the endothelial lining: in veins that are not distended with blood the endothelium may be thrown up into folds. The tunica Media is thin compared with that of arteries and consists of two or more layers of circularly arranged smooth muscle fibers. The tunica Adventitia is the broadest layer of the vessel wall and is composed of longitudinally arranged thick collagen fibers, which merge with the surrounding collagenous tissue. Note that the wall of the vein is thin relative to the diameter of the lumen. In contrast, in most arteries, the thickness of the wall approximates the diameter of the lumen.

The principle differences of arteries and veins:

1.     Thinner wall.

2.     Larger size (diameter).

3.     Irregular shape at the cross section.

4.     Collagen fibers are predominant.

5.     Absence of external elastic membrane and thinner internal one.

6.     The largest tunica is Adventitia.

7.     Valves presence in veins.

 

Large veins such as the femoral and renal veins have a relatively thick muscular wall consisting of several layers of smooth muscle separated by layers of collagenous connective tissue. The tunica Media and tunica Intima also contain a few elastic fibres but there is no distinct internal elastic lamina as in arteries of comparable size. The tunica Adventitia is broad and contains numerous vasa vasorum reflecting the need for arterial blood by the tissues of the vein wall. Vasa vasorum as well as lymphatics also penetrate the whole thickness of the muscular wall and are much more numerous than in arterial vessels of similar size.

The largest vessels of the venous system, the venae cavae, have a structure similar to that just described except that the smooth muscle is disposed longitudinally rather than in a circular fashion. This arrangement may reflect the need for elongation and shortening to accommodate chest expansion and contraction during the respiratory cycle.

 
The lymph vascular system

 

In addition to blood vessels, the human body have a system of endothelial- lined thin-walled channels that collect drain excess fluid, the lymph, from extracellular spaces and returns it to the blood vascular system. Unlike the blood, lymph circulates in only one direction – toward to the heart. Lymph is formed in the following manner. At the arterial end of blood capillaries, the hydrostatic pressure of blood exceeds the colloidal osmotic pressure exerted by plasma proteins. Water and electrolytes therefore pass out of capillaries into the extracellular space, some plasma proteins also leak out through the endothelial wall. At the venous end of blood capillaries, the pressure relationships are reversed and fluid tends to be drawn back into the blood vascular system. In this way, about two percent of plasma passing through the capillary bed is exchanged with the extracellular tissue fluid. The rate of tissue fluid formation at the arterial end of capillaries generally exceeds there-uptake of fluid at the venous end. Lymph capillaries converge to fora progressively larger diameter lymphatic vessels. As in veins, lymphatic circulation is aided by the action of the external forces (e.g., contraction of surrounding skeletal muscle) on their walls. These forces act discontinuously, and indirectional lymph flow is mainly a result of the presence of many valves in these vessels. Contraction of smooth muscle in the walls of larger lymphatic vessels also helps to propel lymph toward the heart.

  Lymph enters the venous system by a single vessel on each side of the body, namely the thoracic duct (on the left) and the right lymphatic duct. Movement of lymph in the lymph vascular system is similar to movement of blood in the venous system but valves are more numerous in lymphatic vessels. Along the course of the larger lymphatic vessels are aggregating of lymphoid tissues called lymph nodes where lymph is sampled for the presence of foreign material (antigen) and where activated cells of the immune system and antibodies join the general circulation.     Lymphatic vessels are found in all tissues except the central nervous system, cartilage, bone, bone marrow, thymus, placenta, cornea and teeth.

 

 

Two lymphatic vessels (LV). The vessel on top was sectioned longitudinally and shows a valve, the structure responsible for the unidirectional flow of lymph. The solid arrow shows the direction of the lymph flow, and the dotted arrows show how the valves prevent lymph backflow. The lower small vessel presents a very thin wall.  PT stain. Medium magnification.

 

 The structure of lymphatic vessels conforms closely to that of vessels of similar diameter in the venous system. Lymphatic vessels may be distinguished from venous vessels by the absense of erythrocytes and the presence of small numbers of leucocytes mainly lymphocytes. Lymphatic capillaries differ from blood capillaries in several respects which reflact the greater permeability of lymphatic capillaries. In particular, the endothelial cell cytoplasm of lymphatics is extremely thin and has no fenestrations. There are no zonula occludens between neighboring cells, the basement membrane is rudimentary or absent and there are no pericytes. Fine collagen filaments known as anchoring filaments link the endothelium to the surrounding supporting tissue preventing collapse of the lymphatic lumen.

 

Lymphatic vessel with a connective tissue. wall even thinner than a vein. There is a cut leaflet of a valve across the lumen. Material in the lumen contains no r.b.c.'s, mostly just structureless lymph and some lymphocytes. There are some fat cells and lymphocytes in the surrounding connective tissue.

 

The larger lymphatic vessels have a structure similar to that of veins except that they have thinner walls and lack a clear-cut separation between layers (Intima, Media, Adventitia). They also have more numerous internal valves. The lymphatic vessels are dilated and assume a nodular, or beaded, appearance between the valves.

The structure of the large lymphatic ducts (thoracic duct and right lymphatic duct) is similar to that of veins, with reinforced smooth muscle in the middle tunic. In this layer, the muscle bundles are longitudinally and circularly arranged, with longitudinal fibers predominating. The Adventitia is relatively undeveloped, like arteries and veins, large lymphatic ducts contain vasa vasorum and a rich neural network.

 

Higher power of valve made of a core of fine c.t. with endothelium covering both surfaces. Valves in veins are constructed similarly.

 

Small blood vessels, with 3-layered walls:

These vessels are often found running together in the c.t. coats of body organs.

Structure of a lymphatic capillary at the electron microscope level. Note the overlapping free borders of endothelial cells, the discontinuous basal lamina (arrows), and the attachment of anchoring fibrils (AF).

 

Heart

 

Heart is the hollow muscular organ, which lies in the mediastinum of the thoracic cavity and is cowered with pericardium. It has right and left portions, each of them consist of two chambers separated with valves. Two more valves are disposed at the entrance of Aorta Pulmonary Artery. The main function of the heart is pumping the blood through the circulatory system by means of rhythmical contractions. It is also responsible for producing a hormone called atrial natriuretic factor. Its walls consist of three tunics: the internal or Endocardium: the middle or Myocardium; and the external, or Pericardium. The central fibrous region of the heart, the fibrous skeleton, serves as the base of the valves as well as the site of origin and insertion of the cardiac muscle cells. The central fibrous body is located at the level of the cardiac valves. Extensions of the central fibrous body surround the heart valves to form the valve rings (annuli fibrosi), which support the base of the valve. A downward extension of the fibrocollagenous tissue of the aortic valve ring forms the membranous interventricular septum between the right and left ventricles. These structures consist of a dense connective tissue, with thick collagen fibers oriented in various directions. Certain regions contain nodules of fibrous cartilage.

Origin. The primitive heart appears in embryo at the beginning of the 3rd week, when two mesenchymal tubes are formed. Later these structures will be cowered with visceral mesoderm. Thus, endocardium takes its origin from mesenchyme (similar to vessels), myocardium and pericardium are developing from the Myoepicardial lamina of mesoderm.

 

 

The heart wall, like blood vessels in general, has three main layers, though they are not called intima, media, and adventitia. As in vessels, however, the innermost and outermost layers are primarily connective tissue; the middle one is muscle --- in this case, cardiac muscle. From left to right, then, in this picture of ventricle wall, there is first a very thin endocardium, which consists primarily of an endothelial lining and a very small amount of connective tissue underneath it. The muscle layer, or myocardium is next and is by far the thickest layer and constitutes the bulk of the heart. To the far right is the epicardium, which contains considerable fat. In gross anatomy the epicardium is called the visceral layer of the serous pericardium; it has an outermost lining layer of mesothelium.

 

A high magnification reminder of the appearance of cardiac muscle cut longitudinally, with central nucleus, branching fibers, and cross-striations. Muscle fibers spiral around the heart in all directions and can thus exert the necessary squeezing action as the heart contracts. Remember that these muscle cells are attached end to end by junctions at the intercalated disc. Axon terminals of autonomic neurons innervate some of the muscle cells, and the stimulus is spread to neighboring muscle cells by the intercalated discs and by gap junctions along the side walls of the cells.

 

Cardiac muscle in cross-section. Note also the many cross cut capillaries in the connective tissue endomysium between muscle fibers. As you might expect from the constant work the heart performs, it is a highly vascularized organ. Capillaries in this (or any) muscle have endothelium that is continuous and non-fenestrated.

 

The tunica Intima of the heart, the Endocardium consists of an endothelial lining and its supporting tissue. It is homologous with Intima of the blood vessels. It lines the chambers of the heart and varies in thickness in different areas, being thickest in the atria and thinnest in the ventricles, particularly the left ventricle.  Endocardium consists of 4 layers: endothelial, subendothelial, muscular-fibrous and outer connective tissue layer. The first one is presented with single layer of squamous endothelial cells resting on a basement membrane. Loose connective tissue of a subendothelial layer contains elastic and collagen fibers. The next more robust fibro-elastic layer contains smooth muscle cells and elastic fibers. This accommodates movement of the myocardlum without damage to the endothelium. The deepest aspect of the endocardium (the outer connective tissue layer may also contain a small amount of adipose tissue. The subendothelial tissue becomes continuous with the perymyslum of the cardiac muscle. The endocardium contains blood vessels, nerves and branches of the conducting system of the heart.

The valves of the heart consist of leaflets of collagenous tissue. The surfaces being invested with a thin endothelial layer continuous with that of the heart chambers and great vessels. At the attached margins of each valve, the lamina fibrosa becomes condensed to form a fibrous ring (valve annulus) and the rings of the four valves together form a central fibrous cardiac "skeleton" which is continuous with the collagenous tissue of the myocardlum, endocardium and epicardium. The mitral and tricuspid leaflets are connected to the papillary muscles by collagenous strands, the chordae tendinae, which also merge with the fibrous lamina of the valve leaflet. The heart valves prevent blood flowing back into the heart chambers after empting.

 

 

The surface of the ventricular lumen is very irregular because of the presence of papillary muscles in the wall. These irregularities are, of course, lined with endothelium.

 

 

Low power of a Mallory-stained heart, showing two channels (above) that are continuous with the lumen of the left ventricle (below). The left-hand channel is the aorta, with some blue connective tissue in its wall. There is also one cusp of the semilunar valve, with its blue core of dense collagen. Remember that valves are lined over their entire surface by endothelium which is continuous with aortic endothelium above and the ventricular endothelium below. To the right in this picture is the atrioventricular channel, with chordae tendinae extending down from the mitral valve and attaching to the papillary muscles of the ventricle. Like valves, the chordae tendinae are also composed of dense collagenous connective tissue covered by an endothelial lining.

 

The middle tunic of the heart, Myocardium, is the thickest tunic and is made up of cardiac muscle, the structure of which meets the unique functional requirements of the heart. Cardiomyocyte is the morphofunctional unite (MPU) of the cardiac muscular fibers. Cardiac muscle cells arranged in layers that surround the heart chambers in a complex spiral. A large number of these layers insert themselves into fibrous cardiac skeleton. The arrangement of these muscle cells is extremely varied, so that in histologic preparations of small area, cells are seen to be oriented in many directions. The muscle cells of the heart are grouped into two populations: contractile cells and the impulse generating – conducting cells responsible for the electrical signal that initiates the heartbeat.

 

Contractile Myocardium has muscular fibers, which consist of cardiomyocytes; each of them is of cylindrical shape (50-120 ìm long and 15-20 in diameter) and is covered with sarcolemma, which consists of plasmalemma and basement membrane. There is one or two centrically disposed nuclei and a lot of mitochondria and glycogen inclusions in the cytoplasm. Presence of myoglobin (special pigmental protein inclusion) is the specific feature of cardiomyocytes. It is the source of oxygen in the contraction. Intercalated disks interconnect the cells. There are a lot of anastomoses between the nearest muscular fibers. Thus myocardium is some kind of a functional syncytium, which allows him to pass the impulses and to contract very simultaneously and quickly.

 

Myoendocrine ce4ll of the heart

 

There are some specific cells of irregular shape with processes in the atria. They have a well-developed rough endoplasmic reticulum, Golgi apparatus and neuroendocrine granules, which is known as atrial natriuretic factor, hormone that can regulate the volume of extracellular fluid and blood pressure. It increases the excretion of water and sodium and potassium ions by the distal convoluted tubule of the kidney. It also inhibits rennin secretion by the kidneys and aldosterone secretion by the adrenal glands.

 

 

Conducting system of the heart

 

The coordinated contraction of the myocardium during each pumping cycle is mediated by a specialized conducting system of modified cardiac muscle fibers. With each cardiac cycle, a wave of excitation originates in the pacemaker region of the right atrium the sino-atrial node: the excitatory stimuli arise spontaneously at a regular interval, the rate being modulated by the autonomic nervous system. The wave of excitation spreads throughout the atria causing there to contract thus forcing blood into the ventricles, by this taxes, the wave of excitation has spread to the atrioventricular node from which an excitatory stimulus is passed rapidly throughout the whole ventricular myocardium via the atrioventricular bundle or bundle of His. This bundle divides within the interventricular septum to give rise to smaller branches called Purkinje fibers, which pass in the subendocardial supporting tissue before penetrating the ventricular myocardium. This system permits coordinated contraction of the entire ventricular myocardium.

The conducting cells are larger than myocardial cells, and sometimes binucleate. The extensive pale cytoplasm contains relatively few myofibrils, which are arranged in an irregular manner immediately beneath the plasma membrane of the cell. The cytoplasm is rich in glycogen and mitochondria but, in contrast to other cardiac muscle cells, there is no tubule system. Connections between the Purkinje cells are via desmosomes and gap junctions rather than by intercalated discs as in the rest of the myocardium. The exitatory cells of the sinoatrial and atrioventricular nodes are small specialized myocardial fibers with electrochemical stimuli being transmitted via gap junctions. The cells contain little contractile protein or glycogen and are embedded in dense collagenous tissue containing numerous autonomic nerve fibers.

There are 3 types of conducting cells: pacemakers, intermediate and cells of  Purkinje fibers. First ones lie at the center of sinoatrial and atrioventricular nodes and 60-80 times per minute are changing polarities of their membrane thus producing stimuli for heart contractions.

 

 

Bundle of His arises from atrioventricular node and lies in the interventricular septa. Then it is branching into 2 “feet” and at last cells of Purkinje fibers, which are placed between endocardium and myocardium, send stimuli to contractile cells.

These large oxyphilic cells have homogenous cytoplasm enriched with glycogen and nuclei which usually are excentrically placed in cell. Few myofibrilles have no regular location. These cells are closely packed in fibers-like aggregations which are well visible in the cross section of heart wall.

One more type of cardial cells – myoendocrine cells or secretory cardiomyocytes. Cells of this type are mainly disposed in atria and auricles of heart. They have basophilic cytoplasm with few myofibrilles and well developed endoplasmic reticulum. Cytoplasm contains small osmiophilic granules containing Na-uretic factor, cardiodilatin and cardionatrin. These hormones allow to increase urine production, so, volume of blood decreases and heart may work easily.

 

 

          Inner surface of the heart, with pale, large Purkinje fibers lying in the subendocardial layer. Endocardium (or intima) is above. The beginning of the myocardium (media, cardiac muscle) is below.

 

The heart is enclosed within the pericardial sac, which is composed of compact fibrocollagenous and elastic tissue, and lined internally by a layer of flat mesothelial cells, also termed the pericardium.

The pericardial cavity is the space between the parietal and visceral pericardial layers. It contains a small amount of serous fluid to lubricate the surface and permit friction-free movement of the heart within the cavity during its muscular contractions.

The epicardium forms the outer covering of the heart and has an external layer of a flat mesothelial cells. These cells lie on a stroma of fibrocollagenous support tissue, which contains elastic fibers, as well as the large arteries supplying blood to the heart wall, and the larger venous tributaries carrying blood from the heart wall. The large arteries (coronary arteries) and veins are surrounded by adipose tissue, which expands the pericardium.

The coronary arteries originate from the first part of the aorta just above the aortic valve ring and pass over the surface of the heart in the pericardium (with autonomic nerves), sending brunches deep into myocardium. This superficial location of the arteries is of great importance since it permits surgical bypass grafting of blocked arteries.

 

Students’ Practical Activities:

Students must know and illustrate such histologic specimens:

Specimen 1. Muscular artery.

Stained with haematoxylin and eosin.

 

 

At a low magnification artery is round or oval-shaped. Its wall consists of three tunics: outer, middle and inner. At a high magnification it is seen that lumenal surface of inner tunic is cowered by the endothelial cells, then subendothelial layer and inner elastic membrane are disposed. The widest middle tunic predominantly consists of smooth myocytes, which are disposed circularly. There are a few elastic fibers between them. Thin outer elastic membrane separates the middle tunic from the outer one. The last tunic (adventitia) is composed of a loose connective tissue.

Illustrate and indicate: 1.Tunica intima: a) endothelial layer; b) subendothelial layer; c) internal elastic lamina. 2. Tunica media: a) smooth muscle cells. 3. Adventitia.

   

   Specimen 2. Elastic artery: aorta.

       Stained with orcein-haematoxylin.

 

 

       At a low magnification the wall of aorta is easily identified compare to the muscular artery ones by the structure of the middle tunic, which has a lot of elastic membranes. Watch the specimen at a high magnification; draw the wall of the aorta.

Illustrate and indicate: 1. Tunica intima: a) endothelium nuclei. 2. Tunica media: a) elastic membranes. 3. Adventitia: a) “vessels of vessels”.

 

Specimen 3. Muscular vein.

Stained with haematoxylin and eosin.

 

At a low magnification let you recognize the vein and middle sized artery. The lumen of the vein (left) is larger and flattened.the inner tunic of the vein has no elastic membrane, the middle one is much more thinner than in muscular artery (middle). Adventitia of the vein is thick and contains smooth myocytes. Watch the specimen at a high magnification, paint the wall of the vein.

Illustrate and indicate: 1. Tunica intima: a) endothelial layer; b) subendothelial layer. 2. Tunica media. 3. Adventitia.

 

Specimen 4.  Arterioles, venules, capillaries (total specimen of the pia mater).

Stained with haematoxylin and eosin.    

 

 

          At a low magnification special attention should be paid on the dense network of hemocapillaries. At a high magnification let you identify the arteriole, capillary and venule due to the wall structure peculiarities. In the wall of arteriole the cross striations may be observed because of circular disposition of the smooth myocytes. Venules have larger diameter, smooth myocytes almost are absent in the wall, there are a lot of blood cells in the lumen. Capillaries in the specimen have a small size and thin wall (which consists of one layer of the endotheliocytes).

Illustrate and indicate: 1. Arteriole: a) endothelium nuclei; b) smooth muscle cells nuclei. 2. Venule: a) endothelium nuclei; b) adventitial cells nuclei; c) blood cells. 3. Capillaries: a) endothelium; b) blood cells.

 

Specimen 5.  Lymphatic capillaries.

Stained with haematoxylin and eosin.    

 

          At a low magnification lymphatic capillary diameter is much larger then the hemocapillary. At a high magnification it is seen, that lymphatic capillary wall has only endothelial cells.

       Illustrate and indicate:  1. Endothelium nuclei. 2. Capillary lumen.

 

Specimen 6. Endocardium.

Stained with haematoxylin and eosin.

 

 

          The endocardium, the innermost layer of the heart, consists of an endothelial lining and its supporting connective tissue. The endothelium is supported by a delicate layer of the connective tissue. The subendothelial connective tissue becomes continuous with the perimysium of the cardiac muscle. The endocardium contains blood vessels, nerves and branches of the conducting system of the heart (modified cardiac muscle fibers).

          Modified cardiac muscle fibers (Purkinje fibers) cross in the subendocardial connective tissue before penetrating the ventricular myocardium. The conducting cells are large, sometimes binucleate, with extensive pale cytoplasm containing relatively few myofibrils which are arranged in an irregular manner immediately beneath the plasma membrane of the cell. The cytoplasm is rich in glycogen and mitochondria but in contrast to cardiac muscle cells, there is no T tubule system. Connections between the Purkinje cells are via desmosomes and gap junctions rather than by intercalated discs as in the myocardium.

Illustrate and indicate: I.Endocardium. 1.Endothelium; 2.Subendothelial layer; 3.Muscular-elastic layer; 4.External layer of the loose connective tissue. 5.Purkinje fibers (modified cardiac muscle fibers).

Specimen 7. Myocardium.

 Stained with   iron haematoxylin.

 

 

The tunica media of the heart is called the myocardium and is thickest in the ventricular walls. The myocardium is made up of cardiac muscle, the structure of which meets the unique functional requirements of the heart. In the specimen cardiac muscle is composed of cardiac muscle cells, which are seen to contain one nuclei and an extensive cytoplasm which branches to give the appearance of a continuous three-dimensional network. The elongated nuclei are mainly centrally located. The branching cytoplasmic network is readily seen with prominent intercalated disks marking the intercellular boundaries. Note the typical cross-striations. In the specimen one can find the delicate connective tissue, extremely rich in blood capillaries, filling the intercellular spaces.

Illustrate and indicate: 1.Cardiac muscles: a)cardiac muscle cells nuclei; b)myofibrils; c)cross-striations; 2.Intercalated disks; 3.Connections between cardiac muscles fibers; 4.Connective tissue with blood vessels.

 

References:

A – Basic:

1.     Practical classes materials: http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/English/medical/III%20term/14%20Circulatory%20system.htm

2.     Lecture presentations: http://intranet.tdmu.edu.ua/ukr/kafedra/index.php?kafid=hist&lengid=eng&fakultid=m&kurs=2&discid=Histology,%20cytology%20and%20embryology

3.     Stevens A. Human Histology / A. Stevens, J. Lowe. – [second edition]. –Mosby, 2000. – P. 137-158.

4.     Wheter’s Functional Histology : A Text and Colour Atlas / [Young B., Lowe J., Stevens A., Heath J.]. – Elsevier Limited, 2006. – P. 152-167.

5.     Singh I. Textbook of Human Histology with colour atlas / Inderbir Singh. – [fourth edition]. – Jaypee Brothers Medical Publishers (P) LTD, 2002. – P.168-177.

6.     Ross M. Histology: A Text and Atlas / M. Ross W.Pawlina. – [sixth edition]. – Lippincott Williams and Wilkins, 2011. – P.400-440.

 

B – Additional:

1.     Eroschenko V.P. Atlas of Histology with functional correlations / Eroschenko V.P. [tenth edition]. – Lippincott Williams and Wilkins, 2008. – P.171-189.

2.     Junqueira L. Basic Histology / L. Junqueira, J. Carneiro, R. Kelley. – [seventh edition]. – Norwalk, Connecticut : Appleton and Lange, 1992. – P.236-250.

3.     Charts: http://intranet.tdmu.edu.ua/index.php?dir_name=kafedra&file_name=tl_34.php#inf3

4.     Disk:  http://intranet.tdmu.edu.ua/data/teacher/video/hist/  

5.     Volkov K. S. Ultrastructure of cells and tissues – Ternopil : Ukrmedknyha, 1999. – P. 40-47.  http://intranet.tdmu.edu.ua/data/books/Volkov(atlas).pdf

6.       http://en.wikipedia.org/wiki/Circulatory

7.       http://www.meddean.luc.edu/LUMEN/MedEd/Histo/frames/histo_frames.html

8.        http://www.udel.edu/biology/Wags/histopage/histopage.htm