Histology of the Blood Vessels
The blood vessels are made of three layers, called from the luminal side outward, the tunica intima, the tunica media and the tunica adventitia. These three layers are analogous to the endo-, myo- and epicardium, respectively. The thickness of these three layers varies greatly depending upon the size and type of vessel (large, medium & small arteries and veins; capillaries).
- The tunica intima consists of an endothelium (present in all vessels) and any subendothelial connective tissue that may be present (highly variable depending on vessel). The endothelium of vessels entering or leaving the heart is continuous with that of the heart.
- The tunica media is the layer of concentrically-arranged smooth muscle, the autonomic control of which can alter the diameter of the vessel and affect the blood pressure. Smooth muscle cells (in contrast to cardiac and skeletal) have secretory capabilities, and (depending on the vessel), the tunica media contains varying amounts of collagen fibres, elastic fibres, elastic lamellae, and proteoglycans secreted by the smooth muscle cells. The tunica media of arteries is larger than that of veins of similar size.
- The tunica adventitia is made chiefly of longitudinally arranged collagen fibres. It tends to be much larger in veins than arteries.
- Low power view of large vein
- Higher power view of wall of large vein
- Medium Veins
- Medium vein with valve
- High power view of vein wall and valve
- High power view of medium vein
- Medium artery and vein
- Small Veins or Venules
- Arteriole and venules
- Small artery and vein
- Capillaries in longitudinal section
- Section of tongue with capillaries and other blood vessels
Arteries carry blood away from the heart. They are classified into three types according to their size: large or elastic arteries; medium (or muscular or distributive) arteries; and small arteries or arterioles, which are less than 0.5 mm in diameter. These types are all continuous with one another. A characteristic feature of arteries, regardless of size, is a well-defined lumen, rounded or oval, maintained by the muscularity of the vessel wall.
The aorta and its branches (brachiocephalic, subclavian, pulmonary, beginning of common carotid and iliac) are distinguished by their great elasticity. This helps them smooth out the large fluctuations in blood pressure created by the heartbeat. During systole, their elastic laminae are stretched and reduce blood pressure. During diastole, the elastic rebound helps maintain arterial pressure.
Tunica intima: Large arteries often have a large subendothelial layer, which grows with age or disease conditions (arteriosclerosis). Both connective tissue and smooth muscle are present in the intima. The border of the intima is delineated by the internal elastic membrane. The internal elastic membrane may not be conspicuous because of the abundance of elastic material in the tunica media.
Tunica media: This is the thickest of the three layers. The smooth muscle cells are arranged in a spiral around the long axis of the vessel. They secrete elastin in the form of sheets, or lamellae, which are fenestrated to facilitate diffusion. The number of lamellae increase with age (few at birth, 40-70 in adult) and with hypertension. These lamellae, and the large size of the media, are the most striking histological feature of elastic arteries. In addition to elastin, the smooth muscle cells of the media secrete reticular and fine collagen fibers and proteoglycans (all not identifiable). No fibroblasts are present.
Tunica adventitia: This is a relatively thin connective tissue layer. Fibroblasts arethe predominant cell type, and many macrophages are also present. Collagen fibres predominate and elastic fibres (not lamellae) are also present. The collagen in the adventitia prevents elastic arteries from stretching beyond their physiological limits during systole. Blood vessels supplying the adventitia and outer media are also present, these are called vasa vasorum ("vessels of the vessels"). (The inner part of the media is supplied from the lumen via pinocytic transport).
Figure 11 shows a low power view of the aorta (from slide 29). The thickness of the tunica media and the abundance of wavy red elastic lamellae is evident. Elastin is also present in the (partially detached) tunica intima but the endothelium cannot be distinguished. An arteriole (vasa vasorum) is present in the adventitia. The big red lines running across the aorta are artefacts produced where the tissue folded during preparation.
Figure 12 shows a higher power view of the aorta. At this magnification, it is hard to distinguish the tunica intima from the tunica media. (It is easier to do at lower magnification because the staining differences (muscular media more reddish, CT intima more yellowish) are more obvious.) At this magnification, the elastic lamellae are the most conspicuous features of both the intima and media. In addition, some endothelial cell nuclei can be seen. (These are frequently stripped away during preparation, if you dont find them in some areas of your slides, that is what happened.) Pale, purple smooth muscle cells nuclei can be seen mainly in the media, but are also present in the intima. A bit of the collagenous adventitia is seen at the extreme top right. The upper and lower part of the aorta within the field of view are bounded by artefacts (folds in tissue).
The majority of named arteries are medium (muscular or distributive) arteries. There is no sharp dividing line between elastic (large) and muscular (medium) arteries; in areas of transition, arteries may appear as intermediates between the two types. Medium arteries have less elastic tissue than large arteries, the predominant constituent of the tunica media is smooth muscle.
Tunica intima: The tunica intima is thinner than in large arteries, there are fewer smooth muscle cells and less elastic tissue. The outermost part of the intima is defined by a very prominent internal elastic membrane (not obscured by elastic lamellae as in large arteries). The basement membrane of the endothelium may rest directly on the internal elastic membrane, or be separated by a subendothelial layer of CT. The tunica intima increases in thickness with age, and may also become expanded by lipid deposits.
Tunica media: Smooth muscle cells predominate in the tunica media, and little elastic material is present. As in large arteries, no fibroblasts are present. Elastic fibres (few), collagen, and ground substance are produced by the smooth muscle cells. These are arranged in a spiral fashion and their contraction helps maintain blood pressure. In tissue preparation, the internal elastic membrane of the intima appears wavy due to the contraction of the smooth muscle of the media.
Tunica adventitia: The main constituent of the adventitia is collagen fibres, secreted by fibroblasts. Elastic fibres are also present, a concentration of such fibres at the inner boundary of the adventitia is called the external elastic membrane. The external elastic membrane is not as prominent as the internal, and as arteries get smaller (see small arteries, below) disappears much earlier. The tunica adventita is relatively larger than in elastic arteries, it can be up to the same size as the media. It will often blend in with the CT of surrounding structures. Adipose cells may be present.
Figure 13 shows a low power view of a medium artery. Notice how the shape of the vessel is fairly well-defined. The tunica intima cannot be clearly distinguished at this magnification. The muscular tunica media stains reddish, and the internal and external elastic membranes bordering it can be distinguished. The collagenous adventitia blends in with surrounding connective tissue. Two folds and a tear (artefacts) are present in the wall.
Figure 14 shows a higher power view of the wall of a medium or muscular artery. The large media consists mainly of smooth muscle whose nuclei can be discerned with a bit of effort. Fine wavy elastic fibres can also be seen in the media. No endothelial cell nuclei can be clearly seen in the intima, however a subendothelial layer of CT and well-defined internal elastic membrane are present. Part of the adventitia is in the field of view, its external elastic membrane is prominent, and other elastic fibres can be seen within it.
Different textbooks will give slightly different numbers for what constitutes the diameter of small arteries and arterioles. Again there is a gradation to larger vessels. The general construction of small arteries is very similar to that of muscular arteries. The media is still muscular and has up to 8-10 layers of smooth muscle cells. This number is reduced as the arteries get smaller, the smallest arterioles have 1-2 layers of smooth muscle cells. The adventitia becomes thinner and the external elastic membrane disappears. The intima becomes smaller and the internal elastic membrane also eventually disappears. However, it persist much longer than the external, and it is not uncommon to see very small arteries which still have an internal elastic membrane. Small arteries also maintain their shape, and tend to be round or oval.
Figure 15 shows a high power view of a small artery. (It is the vasa vasorum of Fig. 11.) Notice its rounded shape, the muscularity of the media (counting smooth muscle nuclei reveals about 5 or 6 layers of smooth muscle) and the persistence of the internal elastic membrane. Elastic tissue is also seen in the adventitia, an external elastic membrane can almost be imagined toward the bottom of the figure. The endothelial cell nuclei bulge prominently into the lumen (their presence is a matter of luck as they are often removed), but no subendothelial tissue is visible. Red blood cells are present in the lumen.
Figure 16 shows a high power view of a small artery (above) and arteriole (below). (They are vasa vasorum of a large vein.) The arteriole has only 2 layers of smooth muscle. Endothelial cell nuclei can be seen in both cases but the internal elastic membranes have disappeared. The adventitias blend in completely with surrounding CT. Note that even these small vessels retain their shape.
Veins are the vessels that return blood to the heart. Like arteries, they are classified as large, medium and small, and the sizes blend into one another with no sharp demarcations. Although the same layers (intima, media and adventitia) are present, they are often not as well defined as in arteries. A big difference between arteries and veins is the thickness of their walls and the relative amount of muscle tissue (media). In comparably sized vessels, arteries have thicker walls and a much larger media. In veins, the adventitia is larger than the media. Because of these features, veins do not retain their shape. They often appear floppy in sections, and the lumen may not be patent. Veins are frequently of an irregular shape. Veins also have less elastic tissue than do arteries. Even in larger veins, the internal elastic membrane may be poorly developed or absent. (It may also be present, so dont assume something is an artery just because you see elastic tissue.) Valves, which function to prevent the backflow of blood especially in the lower part of the body, are also seen quite frequently in veins. Veins often travel in close proximity to their arterial counterparts, which is convenient for histological comparison.
The large veins are the venae cavae and portal vein and their tributaries.
The tunica intima consists of the endothelial lining with its basement membrane, a small amount of subendothelial connective tissue and some smooth muscle cells. It blends in with the tunica media which is relatively thin, and in addition to smooth muscle cells may contain collagen fibres and some fibroblasts (in contrast with the media of arteries). The most distinguishing feature of large veins is the large tunica adventitia. The adventitia is the thickest layer in large veins and is made of collagen fibres, some elastic fibres and fibroblasts. Prominent bundles of longitudinally-arranged smooth muscle are a distinguishing feature.
Figure 17 shows part of a large vein in cross section. Note that the lumen is irregular, the media is relatively small, and the adventitia, with smooth muscle bundles, is several times as wide as the media. The intima cannot be distinguished at this magnification. The vein is lying in loose connective tissue with some blood vessels and much adipose tissue.
Figure 18 shows a higher power view of the wall of the large vein in Figure 17. The endothelium appears to have been stripped away as no endothelial cell nuclei are identifiable. Bundles of smooth muscle sit in the wavy collagen fibres of the adventitia. Blood vessels (vasa vasorum) are also seen.
The tunica consists of the endothelium and a thin subendothelial layer with smooth muscle cells among the connective tissue elements. A thin internal elastic membrane may or may not be present. (If present, it is not nearly as prominent as in arteries).
The tunica media is much thinner relative to that of an artery, and consists mostly of circularly arranged smooth muscle but also contains collagen fibres. The tunicas intima and media therefore tend to be less distinct from one another than is the case in arteries.
The tunica adventitia is usually thicker than the media and is made up mostly of collagen fibres. It may contain longitudinally oriented smooth muscle bundles. (Remember gradations between the vessels of different sizes are continuous.)
Figure 19 shows a part of a medium vein with a valve. Note the thinness of the veins wall in contrast to the wall of a small artery lying to the left. The two vessels are separated by some adipose tissue. The tunica intima of the vein cannot be distinguished from the media. Its lumen contains a large amount of coagulated blood, and some non-coagulated blood cells toward the top.
Figure 20 shows a high power view of the top part of the vein and the valve seen in Figure 19. A few endothelial cell nuclei can be seen but the intima is not distinct. The valve is a fold of the tunica intima reinforced with connective tissue. The tunica media and tunica adventitia are about the same size, the latter blends merges with the surrounding connective tissue (which in the field of view is adipose tissue). Some coagulated blood can be seen adhering to the right side of the valve, and dispersed to the left of it. Some individual, mainly white, blood cells can be seen at the top.
Figure 21 shows a high power view of another medium vein. The lumen is irregular, and the tunica media and adventitia are about the same size. A few muscle bundles are seen in the adventitia. At the top of the figure, the circularly arranged smooth muscle of the media is broken up with connective tissue (asterisks), creating an indistinct boundary between the media and adventitia. The endothelium has been stripped away and the intima is not distinguishable. Some coagulated blood is seen in the lumen. Adipose tissue and a nerve are seen at the right of the figure.
Figure 22 shows part of the wall of a medium artery and part of its (presumably) accompanying vein. The vein has been cut in a longitudinal section. (The bottom of the vein and surrounding tissue have been damaged, so ignore everything below the upper wall of the vein.) Neither tunica intima (if still present) can be distinguished at this magnification, but the wavy, red internal elastic membrane denoting the outermost part of the intima is seen clearly in the artery. The tunica media of the artery is several times larger than that of the vein, and the shape of its lumen (even though only a bit is visible) is regular. In contrast, the lumen of the vein is wavy. The adventitia of both vessels blends in with the connective tissue through which they are travelling.
Different types of venules are described but are not distinguishable with the light microscope. Post capillary venules (which receive blood from capillaries) have only an endothelial lining (intima) and lack a smooth muscle media. They are surrounded by pericytes, which are undifferentiated mesenchymal cells. The basement membrane of the endothelial cells and pericytes may fuse. It is at the level of post-capillary venules that white blood cells leave the blood to enter the tissue. The endothelium of post-capillary venules is the main site of action for vasoactive agents such as histamine and serotonin which cause extravasation of fluid and WBCs during inflammation or allergic reactions.
Collecting venules have a thin adventitia in addition to the pericytes surrounding the intima. The adventitia consists of of longitudinally arranged collagen fibres with a few elastin fibres.
Muscular venules have 1-3 layers of smooth muscle surrounding the intima, and an adventitia as described above.
When looking at a venule which appears to have a media, it is generally not possible to tell if the nuclei of the media belong to smooth muscle cells or pericytes.
Figure 23 shows one arteriole and two venules lying in some adipose tissue (looks like chicken wire fence). Some endothelial cell nuclei can be seen bulging into the lumen of the arteriole. The wall of the arteriole is seen to be thicker than that of the venules and its lumen is well-defined. The adventitia is not distinct in any of the vessels, and blends in with the little bit of yellowish collagenous CT through which they are running.
Figure 24 shows a small artery and vein found at the periphery of a ganglion (slide 80). These vessels are larger than those in the previous figure but I call them small as the artery has fewer than 8 layers of smooth muscle. Part of another small vein is seen at the bottom left. Red blood cells can be seen in the lumina of all three vessels.
The media of the small artery is much larger than that of the small veins. A few bulgy endothelial cells can be seen in the artery, but otherwise an intima is not distinguishable. Elastic tissue is also not identifiable. A few flattened endothelial cells appear to be present in the vein. The adventitia of the vessels blends in with the surrounding CT. An adventitia is most distinct along the top left of the vein, where it borders on adipose cells.
Capillaries are the smallest diameter vessels and the site of exchange of metabolites between blood and tissues. Capillaries are just wide enough to allow the passage of red blood cells, only one cell at a time. (It is during this squeezing through the capillaries that mis-shapen RBCs, as in sickle cell anemia and thalassemia, rupture.)
Capillaries consist of a single layer of endothelial cells and their basement membrane. The endothelial cells are joined together by tight junctions. At intervals, these tight junctions are interrupted, leaving small spaces allowing the passage of fluid between blood and ECF. These interruptions do not occur in the brain, and the lack thereof is responsible for the blood-brain barrier present in most of the brain. Endothelial cells also have pinocytotic vesicles which are involved in transporting macromolecules.
Capillaries are classified according to the structure of their endothelial cells.
- Continuous capillaries (most capillaries) have a continuous endothelial cells with no fenestrations (openings) in their walls. They are found in nervous tissue, muscle tissue, lung, connective tissue and exocrine glands.
- a. Fenestrated capillaries have endothelial cells in which are found small openings, called fenestrae, of about 80- 100 nm in diameter. The fenestrations are covered by a small non-membranous diaphragm (which may be the remnant of the glycocalyx enclosed by pinocytotic vesicles from which the fenestrae may be formed). The basement membrane of endothelial cells is continuous over the fenestrae. Fenestrae allow greater permeability and the rapid passage of macromolecules smaller than plasma proteins. Fenestrated capillaries are found in the intestine and endocrine glands.
b. A special type of fenestrated capillary with no diaphragm is found in the renal glomerulus. This capillary has a thick basement membrane.
- Sinusoids, also called discontinuous capillaries, have a large lumen and follow a tortuous path. They have many fenestrations with no diaphragm , and a discontinuous or absent basal lamina. The lumen is lined with phagocytic cells. They are found in the liver, hematopoietic organs (bone marrow, spleen) and some endocrine organs.
At intervals, the endothelial cells of capillaries may be surrounded by pericytes, undifferentiated mesenchyme cells (as in post-capillary venules). Pericytes can differentiate into fibroblasts and smooth muscle cell, and function in wound repair and the formation of new vessels. Pericytes are associated much more frequently with continuous than with fenestrated capillaries.
It is not possible to distinguish different types of capillaries (except sinusoids) with the light microscope. They are recognized by their small (1 RBC) diameter and thin wall.
Figure 25 shows some capillaries in longitudinal section running along nerve cell bodies (somata) and fibres in a ganglion (slide 80). Note how the red blood cells are stacked one on top of another in the capillaries. Some endothelial cell nuclei can be seen. In addition to the capillaries, some larger blood vessels can be seen.
Figure 26 shows a section through muscle tissue with capillaries and larger blood vessels from the tongue (slide 92; the tissue at the top right is nervous tissue). The blood vessels are expanded and blood cells are absent because the specimen has been perfused. The smallest circles are the capillaries, often an endothelial cell nucleus can be seen. Circles that are larger than the size of a single red blood cells are larger blood vessels.
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