6.2 Erythrocytes (Red Blood Cells)

Red blood cells, or erythrocytes, make up 45% of the volume of human blood. There are about 25 trillion erythrocytes in the body, and each cubic millimeter of blood contains about 5 million erythrocytes. The average man has about 5.5 million erythrocytes per cubic millimeter of blood, and the average woman has about 4.8 million. Erythrocytes measure about 7 micrometers in diameter, and about 2 micrometers thick. If 6 red blood cells were placed in a row, they would reach across the period at the end of this sentence.

In image 6.2a, note that the erythrocyte is shaped like a disk and is slightly concave on top and bottom, like a doughnut without the hole poked completely through. This shape provides a larger surface area for gas diffusion than a flat disk or a sphere and it allows the erythrocyte to fold as it passes through narrow capillaries. As the red blood cell matures, it destroys most of its own organelles--such as, its nucleus, mitochondria, Golgi, etc.--and fills its cytoplasm with mostly hemoglobin molecules and some important enzymes. Image 6.2b is a mature erythrocyte. In the disease called sickle cell anemia, some of the red blood cells are abnormally shaped. A genetic defect, which substitutes an amino acid in the beta chains of hemoglobin, causes the hemoglobin molecules to collapse, and that can result in the collapse of the entire red blood cell, producing the classic "sickle" shape. Image 6.2c includes examples of this deviant shape of red blood cells, which can result in the blockage of blood vessels.

Because red blood cells are specialized for a gas transport function, almost the entire weight of an erythrocyte consists of hemoglobin, an oxygen-carrying complex of globular proteins. The function of hemoglobin is to pick up oxygen that has been inhaled into the lungs, to transport it via the blood vessels to body tissues, and to release it to the tissues as needed. Hemoglobin also carries waste carbon dioxide from the tissues to the lungs, where the gas is exhaled. Hemoglobin is enclosed inside the red blood cells because free hemoglobin molecules could leak through the wall of blood vessels and be lost in the urine. Also, if they were floating free in the blood plasma, they would make the blood too thick, raising its viscosity and its osmotic pressure, all of which would strain the heart.

To maintain normal quantities of erythrocytes, the body must produce new mature cells at the astonishing rate of 2 million per second. In the human adult, blood production takes place in the red bone marrow in the spongy bone of the cranium, ribs, sternum, and bodies of the upper vertebrae.

6.3 Leukocytes (White Blood Cells)

The leukocytes of the blood are classified primarily on the basis of the shape of their nucleus and on the content and staining reaction of their cytoplasm. Image 6.3a shows the inside of an arteriole where the leukocytes ("Le"), tunica intima ("TI")- which is the inner surface layer of the arteriole, and biconcaved-shaped erythrocytes ("BE") are labeled. Image 6.3b shows a light micrograph of two kinds of leukocyte-the lymphocyte (labeled "a"), seen with a large spherical nucleus, and the monocyte (labeled "b"), a larger cell with a C-shaped nucleus. Leukocytes can move in an amoeboid fashion and can squeeze through pores in capillary walls to get to a site of infection. This movement of leukocytes through capillary walls is called diapedesis.

Leukocytes are classified according to their stained appearance. Those leukocytes that have granules in their cytoplasm are called granular leukocytes, and those that do not are agranular leukocytes. The granular leukocytes are also identified by their odd-shaped nuclei, which are often twisted into lobes separated by thin strands. The granular leukocytes are therefore known as polymorphonuclear leukocytes.

There are two types of agranular leukocytes: Iymphocytes and monocytes. Monocytes (image 6.3c) are the largest of the leukocytes and generally have kidney or horseshoe-shaped nuclei. These cells are voracious phagocytes that are capable of ingesting up to 100 bacteria before self-destructing. Lymphocytes (image 6.3d), on the other hand, are smaller cells with large round nuclei surrounded by a halo of cytoplasm. 

Granular leukocytes with granules that have little affinity for stains are called neutrophils. Neutrophils (image 6.3e) are the most abundant type of leukocyte, comprising 50%-70% of the leukocytes in the blood. Note the multi-lobed nucleus and the poorly stained granules. Granular leukocytes with pink-staining granules are called eosinophils (image 6.3f). Note the striking presence of the pinkish granules in the cytoplasm and the multilobed nucleus. Finally, leukocytes with blue-staining granules are called basophils (image 6.3g). These cells are believed to be immature forms of mast cells which are known to secrete anticoagulants and inflammatory substances into the blood.

6.4 Thrombocytes (Platelets)

Thrombocytes (image 6.4a) are the smallest of the formed elements of the blood and are actually fragments of large cells called megakaryocytes, found in bone marrow. The fragments that enter the circulation as platelets lack nuclei but, like leukocytes, are capable of amoeboid movement. Image 6.4b shows a purple mass of thrombocytes, indicated at the tip of the arrow. The platelet count is about 300,000 per cubic millimeter of blood, so they are much less numerous than red blood cells.

Platelets survive about five to nine days and then are destroyed by the spleen and liver. Platelets play an important role in blood clotting. They constitute the major portion of the mass of the clot, and phospholipids in their cell membranes serve to activate the clotting factors in plasma that result in the formation of the threads of fibrin that reinforce the platelet plug. Platelets that clump together in a blood clot release a chemical called serotonin, which stimulates constriction of nearby blood vessels and therefore restricts the flow of blood to the injured area.

6.5 Heart Walls

Image 6.5a is an illustration of the layers of the heart wall and image 6.5b is a micrograph of the heart wall. The wall of the heart has three layers: (1) a thin inner layer called the endocardium (the web-like layer on the right side of image 6.5a and the layer labeled "c" in image 6.5b); (2) a thick middle muscular layer called the myocardium (the largest middle layer in image 6.7a and labeled "a" in image 6.5b); and (3) a thin outer layer called the epicardium (the thin layer closest to the myocardium in image 6.5a and the layer labeled "b" in image 6.5b). The heart sits in a protective sac, called the pericardial sac which is the leftmost layer in image 6.5a.

The epicardium in image 6.5c is labeled "a" and has a thin layer of secretory cells (on the left side of image 6.5c), which secretes serous fluid. The darker area to the right is the myocardium (labeled "b" in image 6.5c), which is the engine of the heart.

Select slide 4. In image 6.5d, the endocardium, a thin fibrous layer lined with endothelium, is labeled "b". Next to the endocardium is the myocardium, labeled "a" in image 6.5d.

6.6 Heart Valves

Image 6.6a is an illustration of a heart and image 6.6b is a cadaver heart with the valves identified. There are four heart valves that prevent the backflow of blood within the heart. The two atrioventricular valves (tricuspid and mitral/bicuspid valve) prevent blood from flowing back into the atria from the ventricles when the ventricles are in systole. The two semilunar valves (each containing three, half-moon shaped leaflets) prevent blood from returning to the ventricles from the major arteries when the heart enters diastole. The pulmonary semilunar valve (top in both images 6.6a and 6.6b) blocks the return of blood from the pulmonary artery, while the aortic valve (middle of both  images 6.6a and 6.6b) blocks the return of blood from the aorta. Also shown on the image 6.6a is the attachment of the two coronary arteries (left and right) to the base of the aorta. In image 6.6b, the heart shows three (one left and two right) bypass vessels that have been surgically implanted onto the heart to replace the defective and clogged coronary arteries.

The valve between the left atrium and left ventricle is called the bicuspid (or mitral) valve. Image 6.6b is a frontal section of the heart, showing the position of the bicuspid/mitral valve between the left ventricle (black chamber on the bottom) and the left atrium (white chamber on the top right). Note also on image 6.6b the white tendinous cords, called chordae tendinae, that stretch from the valve into the ventricle. These chordae tendineae are seen attaching to a large papillary muscle that is fixed onto the inner wall of the left ventricle. During ventricular systole, the papillary muscles contract, putting tension on the chordae tendineae which supports the valve cusps and prevents the backflow of blood into the atrium from the ventricle.

Image 6.6d is a composite slide of examples of pulmonary stenosis. These four pictures represent congenital malformations of the pulmonary valve. They all share a "stenosis" or narrowing of the opening of the valve. In the pictures on the top left, top right, and bottom left there is no typical view of a three-leafed valve. They have fused to form nozzle-like structures which produce a very narrow aperture upon opening. The pulmonary valve at the bottom right does present the typical three-leafed structure, but the valve flaps are sealed together in several places, again restricting the opening of the valve.

Image 6.6e is an example of valvular insufficiency. In valvular insufficiency there is an inability for the valve to completely close, thereby allowing blood to backflow during closure. This picture is an example of aortic insufficiency. In some more aged patients the aorta undergoes dilation (note the enlarged aorta in the heart picture on the left) and the valve becomes insufficient (note the hole remaining in the closed aortic valve in the picture on the right).

Image 6.6f is a comparative example of a normal aortic valve, both in the closed and open position. On the left note the complete closure of the valve (all three leaflets tightly apposed to one another) and on the right observe the complete opening (no stenosis) of the valve cusps.

Image 6.6g is an example of an abnormal condition called calcific aortic stenosis. In this disease the valve undergoes degeneration, showing vegetative growths on the valve leaflets that calcify with time. The result is that the valve cannot open completely and presents a stenosis to blood flow.

6.7 Blood Vessels

Large blood vessels called arteries carry the blood away from the heart. The major arteries divide into smaller arteries, then into still smaller arterioles, and finally into tiny capillaries. The capillaries converge into very small vessels called venules, which in turn join to form longer vessels called veins. The major veins return blood to the atria of the heart. Image 6.7a is an electron micrograph showing a medium sized artery (MA) and vein (MV). In general, arteries have thicker walls than veins. Image 6.7b is a micrograph showing an artery (labeled "a") and vein (labeled "b").

Blood vessel walls vary in thickness. This variation is due to the presence or absence of one or more of three layers of tissues and to the differences in their thicknesses. The tunica intima is the innermost layer. It is formed of a layer of simple squamous epithelium called the endothelium, plus a layer of connective tissue and a basement membrane. The endothelium of the tunica intima is the only layer present in vessels of all sizes. Moreover, it is continuous with the endocardium of the heart. The middle layer of blood vessels, the tunica media, is generally quite thick and is composed of smooth muscle fibers (mostly circularly arranged) mixed with elastic fibers. The outermost layer is the tunica adventitia. This relatively thin layer of connective tissue contains elastic and collagenous fibers that run parallel to the long axis of the vessel. The walls of the larger vessels are too thick to be nourished by diffusion from the blood in the vessel. Instead, they are supplied by their own small nutrient vessels--the vasa vasorum--which are located in the tunica externa and arise either from the blood vessel itself or from other vessels located close by.

Image 6.7c is an example of an arteriole (labeled "b") and a venule (labeled "a"). After blood passes through the capillaries it enters a venule. The arterioles play a major role in regulating the flow of blood into the capillaries. When the smooth muscle of the tunica media contracts, the internal cavities, or lumens, of the vessels are narrowed--that is, the vessels undergo vasoconstriction, which restricts the flow of blood into the capillaries. When the muscles relax, the lumens of the arterioles enlarge---that is, the vessels undergo vasodilation, which allows the blood to enter the capillaries freely.

Image 6.7d is an angiogram of blood vessels in the brain. Blood vessels can be visualized in a living person by injecting dyes that are opaque to X-rays into the vessels, and then taking an X-ray. If a blood vessel bursts (called a hemorrhage), extensive tissue damage can result. Image 6.7e shows the damage that occurred in the brain following an intracerebral hemorrhage.

Image 6.7f is a light microscope cross-section slide of a small capillary (labeled "b") and a larger arteriole (labeled "a"). Note the flattened endothelial cells which form the walls of these vessels. These vessels are located inside of a loose connective tissue stroma which also contains several adipose cells (solid pink cells on the bottom and top left of the screen).

Image 6.7g is a more magnified cross-sectional view of a capillary. The arrow points to the thin wall of the capillary, a good example of a simple squamous epithelium. Several blood cells can be seen inside the capillary lumen, and adipose cells can be observed outside of the vessel (top right of image 6.7g). Image 6.7h is an electron micrograph image of capillaries ("Ca") with arterioles ("Ar") and venules ("Ve"). The capillaries are fed blood directly by arterioles and drained by venules, and as the tissue moves, the capillaries are capable of coiling (indicated by the arrows  in image 6.7h). Capillaries can be so small that red blood cells have to pass through them in single file. Because capillaries have extremely thin walls (see capillary wall at tip of arrow in image 6.7h), they are sites at which the exchange of materials between the blood and the interstitial fluid (cells) takes place. Capillary structure varies from one part of the body to another, but, in general, a capillary consists of a single layer of endothelial cells surrounded by a thin basal lamina. There is no tunica media or tunica adventitia present, and a single endothelial cell may form the entire circumference of a capillary. Endothelial cells are held to one another by tight junctions that can form a seal to prevent molecular loss from the blood.

6.8 Arteries and Arterioles

Because different arteries contain varying amounts of elastic and muscle tissue, some are called elastic arteries, and others are called muscular arteries. The large arteries, such as the aorta and its major branches and the pulmonary trunk, are called elastic arteries. The walls of these arteries are composed of the three tunics described earlier--the tunica intima, media, and adventitia; labeled "TI", "TM", and "TA" in image 6.8a, and "a", "b", and "c" in the light microscope image 6.8b, respectively. 

The tunica media of the large arteries is very thick, and in addition to smooth muscle fibers it also contains many elastic fibers. During ventricular systole, elastic arteries are stretched as blood is ejected from the heart. During diastole, the recoil of the elastic arteries helps maintain pressure within the vessels. The tunica media of the walls of most smaller arteries consists almost entirely of smooth muscle cells, with relatively few elastic fibers. Such arteries are called muscular arteries.

Because of the high pressure of the blood inside them, arteries sometimes rupture or balloon out (called an aneurysm, as seen in image 6.8c).

Arteries are also susceptible to a condition called atherosclerosis, in which fat, fiber, and cellular deposits form on the inside surface of the vessel. Image 6.8d shows a large atherosclerotic deposit on the inside of an artery.

When an arterial vessel has a diameter of less than 0.5 mm, it is referred to as an arteriole, as shown in the electron microscope picture (image 6.8e). Arterioles have a relatively thin tunica media (labeled "TM" in image 6.8e) that is composed of 2-3 layers of smooth muscle cells. The sparse tunica adventitia (labeled "TA" in image 6.8e) can be seen with label lines on the fibers that comprise it, and the inner tunica intima (labeled "TI" in image 6.8e) is seen with its epithelial cells (labeled "EC" in image 6.8e) protruding into the arteriole lumen (labeled "Lu" in image 6.8e). In the smallest arterioles-that is, those closest to the capillaries--the external elastic membrane is lost and the tunica media is gradually reduced until it is composed of only a few scattered smooth muscle cells.