Histology_Ross

Histology_Ross. VI: The layer of polymorphic cells contains cells with diverse shapes, many of which have a spindle of fusiform shape. These cells are called fusiform cells. In addition to pyramidal cells, granule cells, and fusiform cells, two other cell types are also present in the cerebral cortex but are not recognizable in this preparation: the horizontal cells of Cajal, which are present only in layer I and send their processes laterally, and the cells of Martinotti, which send their axons toward the surface (opposite to that of pyramidal cells). Layer I of cerebral cortex, brain, human, Luxol fast cells appear as naked nuclei, with the cytoplasm being indistinguishable blue—PAS ×350. from the nerve fibers that make up the bulk of this layer. Also present is a small capillary (Cap). The pink outline of the vessel is due to the PAS stain-This micrograph is a higher power of layer I, the plexiform ing reaction of its basement membrane.


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Histology_Ross. layer. It consists of nerve fibers, numerous neuroglial cells (NN) and occasional horizontal cells of Cajal. The neuroglial Layer II of cerebral cortex, brain, human, Luxol fast blue—PAS ×350. This micrograph shows layer II, the small pyramidal cell layer. Many small pyramidal cells (PC) are present. Granule cells (GC) are also numerous, though difficult to identify here. Layer IV of cerebral cortex, brain, human, Luxol fast prominent. The micrograph also reveals a number of capillaries. Note how blue—PAS ×350. they travel in various directions. This micrograph shows layer IV, the granular layer. Many of the cells here are granule cells, but neuroglial cells are also


Histology_Ross

Histology_Ross. Layer VI of cerebral cortex, brain, human, Luxol fast region. Pyramidal cells (PC) are readily recognized. Other cell types present blue—PAS ×350. include fusiform cells (FC), granule cells, and Martinotti cells. This micrograph shows layer VI, the layer of polymorphic cells, so named because of the diverse shape of the cells in this White matter, brain, human, Luxol fast blue—PAS ×350. the cortex, the cytoplasm of the cell is not distinguishable. Thus, they appear as naked nuclei in the bed of nerve processes. The neuropil is essentially a This micrograph shows the outer portion of the white matter. densely packed aggregation of nerve fibers and neuroglial cells. The small round nuclei (NN) belong to neuroglial cells. As in KEY BV, blood vessel Cap, capillary CC, cerebral cortex FC, fusiform cells GC, granule cells NN, neuroglial nuclei PC, pyramidal cells PM, pia mater V, vein WM, white matter


Histology_Ross

Histology_Ross. KEY BV, blood vessel Cap, capillary CC, cerebral cortex FC, fusiform cells GC, granule cells NN, neuroglial nuclei PC, pyramidal cells PM, pia mater V, vein WM, white matter The cerebellum is a portion of the brain lying behind and below the cerebrum; it serves to coordinate both voluntary movements and muscle function in the maintenance of normal posture. Cerebellum, brain, human, H&E ×40. The cerebellar cortex has the same appearance regardless of which region is examined. In this low-magnification view of the cerebellum, the outermost layer, the molecular layer (Mol), is lightly stained with eosin. Under this is the granular layer (Gr), which stains intensely with hematoxylin. Together, these two layers constitute the cortex of the cerebellum. Deep in the granular layer is Cerebellum, brain, human, H&E ×400.


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Histology_Ross. At the junction between the molecular and granular layers are the extremely large flask-shaped cell bodies of the Purkinje cells (Pkj ). These cells are characteristic of the cerebellum. Each possesses numerous dendrites (D) that arborize in the molecular layer. The Purkinje cell has a single axon that is not usually evident in H&E sections. This nerve fiber represents the beginning of the outflow from the cerebellum. The figure shows relatively few neuron cell bodies, those of the basket cells (BC ), in the molecular layer; they are widely removed from each other and, at another region that stains lightly with H&E and, except for location, shows no distinctive histologic features. This is the white matter (WM ). As in the cerebrum, it contains nerve fibers, supporting neuroglial cells, and small blood vessels, but no neuronal cell bodies. The fibrous cover on the cerebellar surface is the pia mater (Pia). Cerebellar blood vessels (BV ) travel in this layer. (Shrinkage artifact has


Histology_Ross

Histology_Ross. and small blood vessels, but no neuronal cell bodies. The fibrous cover on the cerebellar surface is the pia mater (Pia). Cerebellar blood vessels (BV ) travel in this layer. (Shrinkage artifact has separated the pia mater from the cerebellar surface.) The rectangular area is shown at higher magnification in Figure on right.


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Histology_Ross. best, show only a small amount of cytoplasm surrounding the nucleus. In contrast, the granular layer presents an overall spotted-blue appearance due to the staining of numerous small nuclei with hematoxylin. These small neurons, called granule cells, receive incoming impulses from other parts of the CNS and send axons into the molecular layer, where they branch in the form of a T, so that the axons contact the dendrites of several Purkinje cells and basket cells. Incoming (mossy) fibers contract granule cells in the lightly stained areas called glomeruli (arrows). Careful examination of the granular layer where it meets the molecular layer will reveal a group of nuclei (G ) that are larger than the nuclei of granule cells. These belong to Golgi type II cells. Cerebellum, brain, human, silver stain ×40.


Histology_Ross

Histology_Ross. Cerebellum, brain, human, silver stain ×40. The specimen in this figure has been stained with a silver procedure. Such procedures do not always color the specimen evenly, as do H&E. Note that the part of the molecular layer on the right is much darker than that on the left. A rectangular area on the left has been selected for examination at higher magnification in Figure 4. Even at the relatively low magnification shown here, however, the Purkinje cells can be recognized in the silver preparation because of their large size, characteristic shape, and location between an outer molecular layer (Mol ) and an inner granular layer (Gr). The main advantage of this silver preparation is that the white matter (WM ) can be recognized as being composed of fibers; they have been blackened by the silver-staining procedure. The pia mater (Pia) and cerebellar blood vessels are also evident in the preparation. Cerebellum, brain, human, silver stain ×400.


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Histology_Ross. Cerebellum, brain, human, silver stain ×400. At higher magnification, the Purkinje cell bodies (Pkj ) stand out as the most distinctive and conspicuous neuronal cell type of the cerebellum, and numerous dendritic branches (D) can be seen. Note, also, the blackened fibers within the granular layer (Gr), about the Purkinje cell bodies, and in the molecular layer (Mol) disposed in a horizontal direction (relative to the cerebellar surface). The arrow indicates a T turn characteristic of the turn made by axons of granule cells. As these axonal branches travel horizontally, they make synaptic contact with numerous Purkinje cells. KEY BC, basket cells BV, blood vessels D, dendrites G, Golgi type II cells Gr, granular layer Mol, molecular layer Pia, pia mater Pkj, Purkinje cells WM, white matter arrows: Upper right figure, glomeruli; Lower right figure, T branching of axon in molecular layer rectangular area, areas shown at higher magnification


Histology_Ross

Histology_Ross. The spinal cord is organized into two discrete parts. The outer part, called the white matter of the cord because of its appearance in unfixed specimens, contains ascending and descending nerve fibers. Some of the fibers go to and from the brain, whereas others connect different lev-els of the spinal cord. The inner part of the spinal cord, called the gray matter because of its appearance in unfixed specimens, contains the cell bodies of neurons as well as nerve fibers. The gray matter forms an Hor butterfly-shaped pattern surrounding the central canal. The gray matter is described as having dorsal (posterior) horns and ventral (anterior) horns. The ventral horns contain the large cell bodies of motor neu-rons, whereas the dorsal horns contain neurons that receive, process, and retransmit information from the sensory neurons whose cell bodies are located in the dorsal root ganglia. The size of the gray matter (and, therefore, the size of the spinal cord) is different at different


Histology_Ross

Histology_Ross. information from the sensory neurons whose cell bodies are located in the dorsal root ganglia. The size of the gray matter (and, therefore, the size of the spinal cord) is different at different levels. Where the gray matter contains many large motor nerve cells that control the movement of the upper and lower limbs, the gray matter and the spinal cord are considerably larger than where the gray matter contains only the motor neurons for the muscle of the torso.


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Histology_Ross. Spinal cord, human, silver stain ×16. A cross-section through the lower lumbar region of the spinal cord is shown here. The preparation is designed to stain the gray matter that is surrounded by the ascending and descending nerve fibers. Although the fibers that have common origins and destinations in the physiologic sense are arranged in tracts, these tracts cannot be distinguished unless they have been marked by special techniques, such as causing injury to the cell bodies from which they arise or by using special dyes or radioisotopes to label the axons.


Histology_Ross

Histology_Ross. The gray matter of the spinal cord appears roughly in the form of a butterfly. The anterior and posterior prongs are referred to as ventral horns (VH ) and dorsal horns (DH ), respectively. The connecting bar is called the gray commissure (GC ). The neuron cell bodies that are within the ventral horns (ventral horn cells) are so large that they can be seen even at this extremely low magnification (arrows). The pale-staining fibrous material that surrounds the spinal cord is the pia mater (Pia). It follows the surface of the spinal cord intimately and dips into the large ventral fissure (VF ) and into the shallower sulci. Blood vessels (BV ) are present in the pia mater. Some dorsal roots (DR ) of the spinal nerves are included in the section.


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Histology_Ross. KEY BV, blood vessels DH, dorsal horn DR, dorsal root GC, gray commissure N, nucleus of ventral horn cell NB, Nissl bodies NN, nucleus of neuroglial cell Np, neuropil Pia, pia mater VF, ventral fissure VH, ventral horn arrows, cell bodies of ventral horn cell


Histology_Ross

Histology_Ross. OVERVIEW OF THE CARDIOVASCULAR SYSTEM / 400 HEART / 402 Intrinsic Regulation of Heart Rate / 405 Systemic Regulation of Heart Function / 407 GENERAL FEATURES OF ARTERIES AND VEINS / 408 Layers of Vascular Wall / 408 Vascular Endothelium / 409 ARTERIES / 414 Large Arteries (Elastic Arteries) / 415 Medium Arteries (Muscular Arteries) / 417 Small Arteries and Arterioles / 420 CAPILLARIES / 421 Classification of Capillaries / 421 Functional Aspects of Capillaries / 422 ARTERIOVENOUS SHUNTS / 423 VEINS / 424 Venules and Small Veins / 425 Medium Veins / 425 Large Veins / 425 ATYPICAL BLOOD VESSELS / 426 LYMPHATIC VESSELS / 427 Folder 13.1 Clinical Correlation: Atherosclerosis / 411 Folder 13.2 Clinical Correlation: Hypertension / 416 Folder 13.3 Clinical Correlation: Ischemic Heart Disease / 429


Histology_Ross

Histology_Ross. The cardiovascular system is a transport system that carries blood and lymph to and from the tissues of the body. The constitutive elements of these fluids include cells, nutrients, waste products, hormones, and antibodies. The cardiovascular system includes the heart, blood vessels, and lymphatic vessels. The cardiovascular system consists of a pump represented by the heart and blood vessels, which provide the route by which blood circulates to and from all parts of the body (Fig. 13.1). The heart pumps the blood through the arterial system under significant pressure; blood is returned to the heart under low pressure with the assistance of negative pressure in the thoracic cavity during inspiration and compression of the veins by skeletal muscle. The blood vessels are arranged so that blood delivered from the heart quickly reaches a network of narrow, thin-walled vessels—the blood capillaries—within or in proximity to the tissues in every part of the body.


Histology_Ross

Histology_Ross. In the capillaries, a two-directional exchange of fluid occurs between the blood and tissues. The fluid, called blood filtrate, carries oxygen and metabolites and passes through the capillary wall. In the tissues, these molecules are exchanged for carbon dioxide and waste products. Most of the fluid reenters the distal or venous end of the blood capillaries. The remaining fluid enters lymphatic capillaries as lymph and is ultimately returned to the bloodstream through a system of lymphatic vessels that join the blood system at the junction of the internal jugular veins with the subclavian veins. Normally, many of the white blood cells conveyed in the blood leave the blood vessels to enter the tissues. This occurs at the level of the postcapillary venules. When pathologic changes occur in the body, as in the inﬂammatory reaction, large numbers of white blood cells emigrate from these venules.


Histology_Ross

Histology_Ross. Arteries are the vessels that deliver blood to the capillaries. The smallest arteries, called arterioles, are functionally associated with networks of capillaries into which they deliver blood. The arterioles regulate the amount of blood that enters these capillary networks. Together, the arterioles, associated capillary network, and postcapillary venules form a functional unit called the microcirculatory or microvascular bed of that tissue. Veins, beginning with the postcapillary venule, collect blood from the microvascular bed and carry it away. FIGURE 13.1 • Photograph of the human heart. This specimen was sectioned in the oblique plane to visualize all of the chambers of the heart. The posterior part of the heart is on the left; the anterior part has been removed and is shown on the right. Note the thickness of the ventricular walls and the intermuscular septum. The interatrial septum, which separates the atria, is also visible.


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Histology_Ross. Two circuits distribute blood in the body: the systemic and the pulmonary circulations. Two pathways of circulation are formed by the blood vessels and the heart:  Pulmonary circulation conveys blood from the heart to the lungs and from the lungs to the heart (Fig. 13.2). arch of aorta  Systemic circulation conveys blood from the heart to other tissues of the body and from other tissues of the body to the heart. Although the general arrangement of blood vessels in both circulations is from arteries to capillaries to veins, in some parts of the systemic circulation it is modified so that a vein or an arteriole is interposed between two capillary networks; these vessels constitute a portal system. Venous portal systems occur in vessels carrying blood to the liver, namely, the hepatic portal system (portal vein), and in vessels leading to the pituitary, the hypothalamic–hypophyseal portal system.


Histology_Ross

Histology_Ross. FIGURE 13.2 • Diagram depicting circulation of blood through the heart. Blood returns from the tissues of the body via the superior vena cava and inferior vena cava. These two major venous vessels carry the blood to the right atrium. Blood then passes into the right ventricle and is pumped into the pulmonary trunk before flowing into the pulmonary arteries, which convey the blood to the lungs. The blood is oxygenated in the lungs and is then returned to the left atrium via the pulmonary veins. Blood then passes to the left ventricle and is pumped into the aorta, which conveys the blood to the tissues of the body. From the heart to the lungs and from the lungs to the heart constitutes the pulmonary circulation; from the heart to the tissues and from the tissues to the heart constitutes the systemic circulation.


Histology_Ross

Histology_Ross. The heart lies obliquely, about two-thirds on the left side of the thoracic cavity, in the middle mediastinum—the space enclosed between sternum, vertebral column, diaphragm, and lungs. It is surrounded by a tough fibrous sac, the pericardium, which also contains the beginnings and ends of the great vessels entering and leaving the heart. Through the pericardium, the heart is strongly attached to the diaphragm and neighboring organs that lie in the thoracic cavity. The heart is a muscular pump that maintains unidirectional flow of blood.


Histology_Ross

Histology_Ross. The heart contains four chambers—the right and left atria and right and left ventricles—through which blood is pumped (see Fig. 13.1). Valves guard the exits of the chambers, preventing backflow of blood. An interatrial septum and an interventricular septum separate the right and left sides of the heart. The right side of the heart pumps blood through pulmonary circulation. The right atrium receives blood returning from the body via the inferior and superior venae cavae, the two largest veins of the body (Fig. 13.3). The right ventricle receives blood from the right atrium and pumps it to the lungs for oxygenation via the pulmonary arteries. The left side of the heart pumps blood through systemic circulation. The left atrium receives the oxygenated blood returning from the lungs via the four pulmonary veins. The left ventricle receives blood from the left atrium and pumps it into the aorta for distribution into the remainder of the body.


Histology_Ross

Histology_Ross. FIGURE 13.3 • Diagram of the blood circulation. This diagram shows the right and left side of the heart artificially separated. The right side of the heart pumps blood through the low-pressure pulmonary circulation. The right atrium receives deoxygenated blood returning from the body via the inferior and superior venae cavae. The right ventricle receives blood from the right atrium and pumps it to the lungs for oxygenation via the pulmonary arteries. The left side of the heart pumps blood through the high-pressure systemic circulation. The left atrium receives the oxygenated blood returning from the lungs via the four pulmonary veins. The left ventricle receives blood from the left atrium and pumps it into the aorta for systemic distribution. The heart contains the following:  A musculature of cardiac muscle for contraction to propel the blood.


Histology_Ross

Histology_Ross.  A fibrous skeleton that consists of four fibrous rings surrounding the valve orifices, two fibrous trigones connecting the rings, and the membranous part of the inter-ventricular and interatrial septa. The fibrous rings are composed of dense irregular connective tissue. They encircle the base of the two arteries, leaving the heart (aorta and pulmonary trunk) and the openings between the atria and the ventricles (right and left atrioventricular [AV] orifices) (Fig. 13.4). These rings provide the attachment site for the leaflets of all four valves of the heart that allow blood flow in only one direction through the openings. The membranous part of the interventricular septum is devoid of cardiac muscle; it consists of dense connective tissue that contains a short length of the atrioventricular bundle of the conducting system of the heart. The fibrous skeleton provides independent attachments for the atrial and ventricular myocardium. It also acts as an electrical insulator by


Histology_Ross

Histology_Ross. bundle of the conducting system of the heart. The fibrous skeleton provides independent attachments for the atrial and ventricular myocardium. It also acts as an electrical insulator by preventing the free flow of electrical impulses between atria and ventricles.


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Histology_Ross.  A conducting system for initiation and propagation of rhythmic depolarizations, which results in rhythmic cardiac muscle contractions (Fig. 13.5). This system is formed by modified cardiac muscle cells (Purkinje fibers), which generate and conduct electrical impulses rapidly through the heart. In the sudden cessation of normal heart rhythm leading to abrupt cessation of blood circulation called cardiac arrest, the conducting system of the heart fails to produce or conduct electrical fibrous ring of pulmonary conus trunk ligament left fibrous fibrous ring trigone of tricuspid fibrous ring of mitral valve


Histology_Ross

Histology_Ross. FIGURE 13.4 • Fibrous skeleton of the heart as seen with the two atria removed. This fibrous network (indicated in blue) serves for the attachment of cardiac muscle; it also serves for the attachment of the cuspid valves between the atria and ventricles and for the semilunar valves of the aorta and the pulmonary artery. The atrioventricular bundle passes from the right atrium to the ventricular septum via the membranous septum of the fibrous skeleton. FIGURE 13.5 • Chambers of the heart and the impulse-conducting system. The heart has been cut open in the coronal plane to expose its interior and the main parts of its impulse-conducting system (indicated in yellow). Impulses are generated in the sinuatrial (SA) node, transmitted through the atrial wall to the atrioventricular (AV) node and then sent along the AV bundle to the Purkinje fibers.


Histology_Ross

Histology_Ross. impulses that cause the heart to contract and supply blood to the body. Sudden cardiac arrest is a medical emergency; first-aid treatment such as cardiopulmonary resuscitation (CPR) and defibrillation (delivering a therapeutic dose of electrical energy to the heart) can improve the chances of survival. If not treated, cardiac arrest leads to sudden cardiac death. Heart rhythm pathologies associated with cardiac arrest include tachycardia (accelerated heart rhythm), fibrillation (rapid, irregular, and ineffective contractions), bradycardia (decelerated heart rhythm), and asystole (total absence of heart rhythm).


Histology_Ross

Histology_Ross.  A coronary vasculature that consists of two coronary arteries and cardiac veins. The right and left coronary arteries provide the arterial blood supply to the heart. They originate from the initial part of the ascending aorta near the aortic valves and circle the base of the heart, with branches converging toward the apex of the heart. Venous drainage of the heart occurs via several cardiac veins, most of which drain into the coronary sinus located on the posterior surface of the heart. The coronary sinus drains into right atrium. The wall of the heart is composed of three layers: epicardium, myocardium, and endocardium. The structural organization of the wall of the heart is continuous within the atria and ventricles. The wall of the heart is composed of three layers. From the outside to the inside, they are as follow.


Histology_Ross

Histology_Ross.  The epicardium, also known as the visceral layer of serous pericardium, adheres to the outer surface of the heart (Fig 13.6). It consists of a single layer of mesothelial cells and underlying connective and adipose tissue. The blood vessels and nerves that supply the heart lie in the epicardium and are surrounded by adipose tissue that cushions the heart in the pericardial cavity. The epicardium is reflected back at the great vessels entering and leaving the heart as the parietal layer of serous pericardium, which lines the inner surface of the pericardium that surrounds the heart and roots of great vessels. Thus, there is a potential space containing a minimal amount (15–50 ml) of serous (pericardial) fluid between the visceral and parietal layers of the serous pericardium. This space is known as the pericardial cavity; its lining consists of mesothelial cells (see Fig. 13.6). The condition in which excess ﬂuid (blood or pericardial effusion) rapidly accumulates in the pericardial


Histology_Ross

Histology_Ross. is known as the pericardial cavity; its lining consists of mesothelial cells (see Fig. 13.6). The condition in which excess ﬂuid (blood or pericardial effusion) rapidly accumulates in the pericardial cavity is called cardiac tamponade. It is commonly caused by both blunt and penetrating chest injuries and by myocardial rupture or pericarditis (inﬂammation of pericardium). This is a life-threatening condition in which accumulating ﬂuid compresses the heart, preventing the heart’s chambers from filling properly with the blood. Relieving the pressure is usually accomplished with pericardiocentesis (a procedure to drain the ﬂuid from the pericardial cavity).


Histology_Ross

Histology_Ross.  The myocardium, consisting of cardiac muscle, is the principal component of the heart. The detailed histologic structure and function of cardiac muscle is discussed in Chapter 11, Muscle Tissue. The myocardium of the atria is substantially thinner than that of the ventricles. The atria receive blood from the large veins and deliver it to adjacent ventricles, a process that requires relatively low pressure. The myocardium of the ventricles is substantially thicker because of the higher pressure required to pump the blood through the pulmonary and systemic circulations (Fig. 13.7).


Histology_Ross

Histology_Ross.  The endocardium consists of an inner layer of endothelium and subendothelial connective tissue, a middle layer of connective tissue and smooth muscle cells, and a deeper layer of connective tissue, which is also called the subendocardial layer. The latter is continuous with the connective tissue of the myocardium. The conducting system of the heart (see the following section called “Intrinsic Regulation of Heart Rate”) is located in the subendocardial layer of the endocardium. The interventricular septum is the wall between the right and left ventricles. It contains cardiac muscle in all but the membranous portion. Endocardium lines each surface of the interventricular septum. The interatrial septum is much thinner than the interventricular septum. Except in certain localized areas that contain fibrous tissue, it has a center layer of cardiac muscle and a lining of endocardium facing each chamber.


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Histology_Ross. FIGURE 13.6 • Layers of the heart and pericardium. This schematic diagram shows the anatomical relationship between the layers of the heart. In the middle mediastinum, the heart and roots of the great vessels are surrounded by the pericardium, which is often covered by highly variable amounts of adipose tissue. The pericardium has two layers: a tough external fibrous layer called the fibrous pericardium and a parietal layer of serous pericardium that lines its inner surface. The parietal layer of the serous pericardium is reflected back at the great vessels entering and leaving the heart as the visceral layer of the serous pericardium or epicardium. The epicardium lines the outer surface of the heart. The pericardial cavity is a space between the visceral and parietal layers of the serous pericardium, and it is lined by the mesothelial cells. Deep to the epicardium is the myocardium consisting of cardiac muscle. Note a small amount of adipose tissue of the epicardium, which contains


Histology_Ross

Histology_Ross. pericardium, and it is lined by the mesothelial cells. Deep to the epicardium is the myocardium consisting of cardiac muscle. Note a small amount of adipose tissue of the epicardium, which contains the coronary arteries and cardiac veins. The inner layer of the myocardium is called the endocardium, which is lined by the mesothelium with an underlying thin layer of connective tissue.


Histology_Ross

Histology_Ross. Heart valves are composed of connective tissue with overlying endocardium. The heart valves attach to the complex framework of dense irregular connective tissue that forms the fibrous rings and surrounds the orifices containing the valves (Fig. 13.8). Each valve is composed of three layers.  The fibrosa forms the core of the valve and contains fibrous extensions from the dense irregular connective tissue of the skeletal rings of the heart.  The spongiosa is loose connective tissue located on the atrial or blood vessel side of each valve. It is composed of loosely arranged collagen and elastic fibers infiltrated with


Histology_Ross

Histology_Ross.  The spongiosa is loose connective tissue located on the atrial or blood vessel side of each valve. It is composed of loosely arranged collagen and elastic fibers infiltrated with FIGURE 13.7 • Horizontal section through the ventricles of the heart. This photograph shows a cross section of the human heart at the level of the ventricles. Cusps of both the tricuspid valve in the right ventricle and the mitral valve in left ventricle are visible with their attachments to the chordae tendineae. Cross sections of the papillary muscles in both ventricles are visible. Note the differences in the thickness between the wall of the right and left ventricles. Adipose tissue of the epicardium contains branches of the coronary arteries and tributaries of the coronary veins. RV, right ventricle; LV, left ventricle. (Courtesy of Dr. William D. Edwards, Mayo Clinic, Rochester, MN.)


Histology_Ross

Histology_Ross. FIGURE 13.8 • Photomicrograph of the left atrial and left ventricular walls. a. This photomicrograph shows a sagittal section of the posterior wall of the left atrium and left ventricle. The line of section crosses the coronary (AV) groove containing the coronary sinus and circumflex branch of the left coronary artery. Note that the section has cut through the fibrous AV ring of the mitral valve, which provides the attachment site for the muscle of the left atrium and the left ventricle and the cusp of the mitral valve. The ventricular wall consists of three layers: (1) endocardium (arrowheads), (2) myocardium, and (3) epicardium. The visible blood vessels lie in the epicardium and are surrounded by adipose tissue. The layers of the mitral valve are shown at higher magnification in Figure 13.9b. 35.


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Histology_Ross. b. This high magnification of the area indicated by the rectangle in a shows the characteristic features of the inner surface of the heart. Note that the endocardium consists of a squamous inner layer of endothelium (End), a middle layer of subendothelial dense connective tissue (DCT ) containing smooth muscle cells (SMC), and a deeper subendocardial layer containing Purkinje fibers (PF). The myocardium contains cardiac muscle fibers (CMF) and is seen on the left. 120. large numbers of proteoglycans. The spongiosa acts as a shock absorber to dampen vibrations associated with the closing of the valve. It also confers flexibility and plasticity to the valve cusps. In the aortic and pulmonary valves, spongiosa located on the blood vessel side is called arterialis. It corresponds to the loose connective tissue located on the atrial side of the AV (tricuspid and mitral) valves, which is called the auricularis.


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Histology_Ross.  The ventricularis is immediately adjacent to the ventricular or atrial surface of each valve and is covered with endothelium. It contains dense connective tissue with many layers of elastic fibers. In the AV valves, the ventricularis continues into the chordae tendineae, which are fibrous, threadlike cords also covered with endothelium (Fig. 13.9). They extend from the free edge of the AV valves to muscular projections from the wall of the ventricles, which are called papillary muscles. Valve cusps are normally avascular. Small blood vessels and smooth muscle can be found only in the base of the cusp. The surfaces of the valve are exposed to blood, and the cusps are thin enough to allow nutrients and oxygen to diffuse from the blood.


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Histology_Ross. Several diseases affect the valves of the heart, causing their degeneration (e.g., calcification, fibrosis) and resulting in heart malfunction because of insufficiency or stenosis of valvular orifices. These conditions, known collectively as valvular heart disease, include rheumatic heart disease, vegetative endocarditis, degenerative calcific aortic valve stenosis, and mitral annular calcification. For example, rheumatic fever causes inﬂammation of the heart valves (valvulitis). Inﬂammation induces angiogenesis in the valve and vascularization in the normally avascular layers of the valve. These changes most commonly affect the mitral valve (65% to 70%) and aortic valve (20% to 25%). This inﬂammation can lead to progressive replacement of elastic tissue by irregular masses of collagen fibers, causing the valve to thicken. The valves become rigid and inﬂexible, which affects their ability to open and close. Intrinsic Regulation of Heart Rate


Histology_Ross

Histology_Ross. Intrinsic Regulation of Heart Rate Contraction of the heart is synchronized by specialized cardiac conducting cells. Cardiac muscle can contract in a rhythmic manner without any direct stimulus from the nervous system. For the heart to be an effective pump, it is necessary for the atria and ventricles to contract in a coordinated rhythmic manner. The electrical activity (impulses) that results in the rhythmic pulsations of the heart is initiated and propagated by the conducting system of the heart. The rate of depolarization of cardiac muscle


Histology_Ross

Histology_Ross. FIGURE 13.9 • Mitral valve in the human heart. a. This photograph shows a sagittal section of the posterior wall of the left ventricle and the posterior cusp of the mitral valve. The chordae tendineae extend from the papillary muscle to the ventricular side of the mitral valve cusp. Note the thickness of the myocardium in the left ventricle. Glistening inner surface of the heart represents the endocardium, the outer surface of the myocardium is covered by the epicardium. 2. (Courtesy of Dr. William D. Edwards, Mayo Clinic, Rochester, MN.) b. Photomicrograph of a mitral valve. This photomicrograph shows a section through one of the two cusps of the mitral valve. Both sides of the cusp are covered by the endothelium. Note that the valve exhibits a layered architecture. Beginning at the atrial side (top of the image), the first layer underlying the endothelium is the spongiosa—not well developed in this part of the cusp. The second layer is the fibrosa, which forms the majority of the


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Histology_Ross. side (top of the image), the first layer underlying the endothelium is the spongiosa—not well developed in this part of the cusp. The second layer is the fibrosa, which forms the majority of the dense connective tissue in the core of the valve. The third layer, the ventricularis, is formed by dense connective tissue containing layers of elastic and collagen fibers. 125.


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Histology_Ross. varies in different parts of the conducting system; the fastest is in the atria, the slowest in the ventricles. The contraction cycle of the heart is initiated in the atria, forcing blood into the ventricles. A wave of contraction in the ventricles then begins at the apex of the heart, forcing blood from the heart into the aorta and pulmonary trunk.


Histology_Ross

Histology_Ross. The conducting system of the heart consists of two nodes—the sinoatrial node and the atrioventricular node—and a series of conduction fibers or bundles (tracts). Electrical impulses are generated at the sinoatrial (SA) node, a group of specialized nodal cardiac muscle cells located near the junction of the superior vena cava and the right atrium (see Fig. 13.5). Since the SA node has the fastest rate of depolarizations, it is referred to as the pacemaker of the heart. The pacemaker rate of the SA node is about 60 to 100 beats per minute. The SA node initiates an impulse that spreads along the cardiac muscle fibers of the atria and along internodal tracts composed of modified cardiac muscle fibers. The impulse is then picked up at the atrioventricular (AV) node and carried across the fibrous skeleton to the ventricles by the AV bundle (of His). The bundle divides into smaller right and left bundle branches and then into subendothelial branches, commonly called Purkinje fibers. The


Histology_Ross

Histology_Ross. skeleton to the ventricles by the AV bundle (of His). The bundle divides into smaller right and left bundle branches and then into subendothelial branches, commonly called Purkinje fibers. The components of the conducting system convey impulses at a rate approximately four times faster than the cardiac muscle fibers and are the only elements that can convey impulses across the fibrous skeleton.


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Histology_Ross. If the SA node fails to function (e.g., because of insufficient blood supply), then the area with the next fastest intrinsic rate of depolarization will take over. In this situation, the AV node will drive the heart contractions at a rate of about 50 beats per minute. In complete heart block when the conduction of electric impulses to the ventricles is interrupted, the ventricles will beat at their own rate of about 30 to 40 beats per minute, driven by depolarization of Purkinje fibers. Purkinje fibers have the slowest rate of intrinsic depolarization of the entire conducting system. The spread of electrical impulses through the myocardium can be monitored and recorded by the electrocardiogram (ECG). The ECG is obtained by placing electrodes at different points on the skin at specific distances from the heart. Electrodes record electrical activity of the heart by measuring voltage differences between different points. The coordinated spread of the electrical activity through the heart


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Histology_Ross. from the heart. Electrodes record electrical activity of the heart by measuring voltage differences between different points. The coordinated spread of the electrical activity through the heart is responsible for the shape of the ECG waveform, careful analysis of which can provide information about heart rate, cardiac rhythm, conduction times through various parts of the heart, effects of electrolyte concentration, effects of cardiac medication, and location of pathologic (ischemic) damages in the heart.


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Histology_Ross. The nodal cardiac muscle cells in both the SA and AV nodes are modified cardiac muscle fibers that are smaller than the surrounding atrial cardiac muscle cells. They contain fewer myofibrils and lack typical intercalated discs. The AV bundle, the bundle branches, and the Purkinje fibers are also composed of modified cardiac muscle cells, but they are larger than the surrounding ventricular muscle cells (Fig. 13.10 and Plate 32, page 432). The terminal ramifications of the conducting system consist of Purkinje fibers. Cardiac conducting cells that make up the bundle of His originate at the AV node, pass through the fibrous skeleton of


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Histology_Ross. FIGURE 13.10 • Photomicrograph of the ventricular wall containing the conducting system. This photomicrograph shows a Mallory-Azan–stained section of the ventricular wall of a human heart. The upper two thirds of the micrograph is occupied by the endocardium (E) containing a thick layer of Purkinje fibers. The free luminal surface of the ventricle (top) is covered by endothelium and an underlying layer of subendothelial connective tissue (stained blue). The deep layer of endocardium contains the Purkinje fibers. Note the intercalated discs in the fibers (arrows). The Purkinje fibers contain large amounts of glycogen, which appear as homogeneous, pale-staining regions that occupy the center portion of the cell surrounded by the myofibrils. The nuclei (N) are round and are larger than the nuclei of the cardiac muscle cells in the myocardium (M). They are frequently surrounded by the lighter-stained cytoplasm, which represents the juxtanuclear region of the cell. Because of the


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Histology_Ross. the nuclei of the cardiac muscle cells in the myocardium (M). They are frequently surrounded by the lighter-stained cytoplasm, which represents the juxtanuclear region of the cell. Because of the considerable size of the Purkinje cells, the nuclei are often not included in the section. Among the Purkinje fibers course nerves (NF ) that belong to the autonomic nervous system. 320.


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Histology_Ross. the heart, course along both sides of the interventricular septum (see Fig. 13.5), and terminate as Purkinje fibers in the myocardium of the ventricles. The cells that form the Purkinje fibers are larger than ventricular muscle cells. Their myofibrils are located at the periphery of the cell. The nuclei are round and are larger than the nuclei of the cardiac muscle cells in the myocardium. Because of the considerable size of the cells, the nuclei are often not included in the section. Intercalated disks are present in Purkinje fibers, but they are variable in appearance and number depending on their location. They are positive for periodic acid–Schiff (PAS) staining because of the large amount of glycogen they contain. With hematoxylin and eosin (H&E) and most other stains, the glycogen-rich center portion of the cell appears homogeneous and stains pale (see Fig 13.10). Because of the stored glycogen, Purkinje fiber cells are more resistant to hypoxia than are ventricular muscle


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Histology_Ross. center portion of the cell appears homogeneous and stains pale (see Fig 13.10). Because of the stored glycogen, Purkinje fiber cells are more resistant to hypoxia than are ventricular muscle cells.


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Histology_Ross. Systemic Regulation of Heart Function As mentioned above, the heart beats independently of any nervous stimulation. This spontaneous rhythm of the heart can be altered by nerve impulses from both sympathetic and parasympathetic divisions of the autonomic nervous system. The autonomic nerves do not initiate contraction of the cardiac muscle but rather regulate the heart rate (a chronotropic effect) according to the body’s immediate needs. Stimulation of the parasympathetic nerves decreases the heart rate.


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Histology_Ross. Stimulation of the parasympathetic nerves decreases the heart rate. The parasympathetic nerve supply to the heart originates in the vagus nerve (cranial nerve X). Presynaptic parasympathetic fibers synapse with postsynaptic neurons within the heart. Their short postsynaptic fibers terminate chiefly at the SA and AV nodes but also extend into the coronary arteries that supply the heart. The release of the neurotransmitter acetylcholine from the terminals of these fibers slows the heart rate (an effect known as bradycardia), reduces the force of the heartbeat, and constricts the coronary arteries of the heart. Stimulation of the sympathetic nerves increases the heart rate.


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Histology_Ross. Stimulation of the sympathetic nerves increases the heart rate. The sympathetic presynaptic fibers that supply the heart originate in the lateral horns at the level of the T1 to T6 segments of the spinal cord. They conduct electrical signals to the cell bodies of postsynaptic neurons located in the cervical and thoracic paravertebral ganglia of sympathetic trunks (see Fig. 12.25, page 380). The postsynaptic fibers terminate at the SA and AV nodes, extend into the myocardium, and also pass through the epicardium to reach the coronary arteries. The autonomic fibers secrete norepinephrine that regulates the rate of impulses emanating from the SA node. The sympathetic component causes the rate of contraction to increase (an effect known as tachycardia) and increases the force of muscle contraction. Sympathetic stimulation produces dilation of the coronary arteries by inhibiting their constriction.


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Histology_Ross. The heart rate and the force of contraction can be regulated by circulating hormones and other substances. Changes in the force and rate of cardiac muscle contractions are regulated by hormones secreted from the adrenal medulla. These hormones include epinephrine and norepinephrine that reach the heart muscle cells via the coronary circulation.


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Histology_Ross. Activation of adrenergic receptors (mainly 1 type) by epinephrine and less efficiently by norepinephrine increases the force of contraction (a positive inotropic effect) and the heart rate (a positive chronotropic effect). Other substances that have positive inotropic and chronotropic effects on the heart include Ca2, thyroid hormones, caffeine, theophylline, and the cardiac glycoside digoxin. These substances all increase intracellular Ca2 levels in cardiac myocytes. Substances that have negative inotropic and chronotropic actions on the heart muscle include adrenergic-receptor antagonists such as propranolol or Ca2 channel blockers. These substances decrease the heart rate and the force of cardiac muscle contraction. The central nervous system monitors arterial pressure and heart function through specialized receptors located within the cardiovascular system.


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Histology_Ross. The central nervous system monitors arterial pressure and heart function through specialized receptors located within the cardiovascular system. The activity of the cardiovascular system is monitored by specialized centers in the central nervous system (CNS). Specialized sensory nerve receptors that supply afferent information about blood pressure are located in the walls of large blood vessels near the heart and within the heart itself. The information received from all types of cardiovascular receptors initiates the appropriate physiologic reflexes. The receptors function as follow.


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Histology_Ross. blood pressure. These receptors are located in the carotid sinus and aortic arch.  Volume receptors (low-pressure receptors) located within the walls of the atria and ventricles sense central ve nous pressure and provide the CNS with information about cardiac distention.  Chemoreceptors detect alterations in oxygen, carbon dioxide tension, and pH. These receptors are the carotid and aortic bodies located at the bifurcation of the com mon carotid arteries and in the aortic arch, respectively. The carotid bodies consist of cords and irregular groups of epithelioid cells. A rich supply of nerve fibers is associated with these cells. The neural elements are both afferent and efferent. The structure of the aortic bodies is essentially similar to that of the carotid bodies. Both receptors function in neural reflexes that adjust cardiac output and respiratory rate. Layers of Vascular Wall The walls of arteries and veins are composed of three layers called tunics.


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Histology_Ross. Layers of Vascular Wall The walls of arteries and veins are composed of three layers called tunics. The three layers of the vascular wall, from the lumen outward (Fig. 13.11 and Plate 33, page 434), are the following. FIGURE 13.11 • Schematic diagram of the major structural features of blood vessels. The layers or tunics of the blood vessel walls are labeled in the upper two panels. The arrangement of the microcirculatory bed in certain parts of the body is shown in the lowest panel. Note the location of pericytes and their relationship to the basal lamina. Also, an arteriovenous (AV) anastomosis is shown within the microcirculatory bed.


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Histology_Ross.  The tunica intima, the innermost layer of the vessel, consists of three components: (a) a single layer of squamous epithelial cells, the endothelium; (b) the basal lamina of the endothelial cells (a thin extracellular layer composed chiefly of collagen, proteoglycans, and glycoproteins); and (c) the subendothelial layer, consisting of loose connective tissue. Occasional smooth muscle cells are found in the loose connective tissue. The subendothelial layer of the intima in arteries and arterioles contains a sheetlike layer or lamella of fenestrated elastic material called the internal elastic membrane. Fenestrations enable substances to diffuse readily through the layer and reach cells deep within the wall of the vessel.


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Histology_Ross.  The tunica media, or middle layer, consists primarily of circumferentially arranged layers of smooth muscle cells. In arteries, this layer is relatively thick and extends from the internal elastic membrane to the external elastic membrane. The external elastic membrane is a layer of elastin that separates the tunica media from the tunica adventitia. Variable amounts of elastin, reticular fibers, and proteoglycans are interposed between the smooth muscle cells of the tunica media. The sheets or lamellae of elastin are fenestrated and arranged in circular concentric layers. All of the extracellular components of the tunica media are produced by the smooth muscle cells.


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Histology_Ross.  The tunica adventitia, or outermost connective tissue layer, is composed primarily of longitudinally arranged collagenous tissue and a few elastic fibers. These connective tissue elements gradually merge with the loose connective tissue surrounding the vessels. The tunica adventitia ranges from relatively thin in most of the arterial system to quite thick in the venules and veins, where it is the major component of the vessel wall. In addition, the tunica adventitia of large arteries and veins contains a system of vessels called the vasa vasorum that supplies blood to the vascular walls themselves, as well as a network of autonomic nerves called nervi vascularis that control contraction of the smooth muscle in the vessel walls. Histologically, the various types of arteries and veins are distinguished from each other by the thickness of the vascular wall and differences in the composition of the layers. Table 13.1 summarizes the features of the various types of blood vessels.


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Histology_Ross. In the adult human body, a circulatory system consists of about 60,000 miles of different-sized vessels that are lined by a simple squamous epithelium called endothelium. The endothelium is formed by a continuous layer of flattened, elongated, and polygonally shaped endothelial cells that are aligned with their long axes in the direction of the blood flow. At the luminal surface, they express a variety of surface adhesion molecules and receptors (i.e., low-density lipoprotein [LDL], insulin, and histamine receptors). Endothelial cells play an important role in blood homeostasis. The functional properties of these cells change in response to various stimuli. This process, known as endothelial activation, is also responsible for the pathogenesis of many vascular diseases (e.g., atherosclerosis; Folder 13.1). Inducers of endothelial activation include bacterial and viral antigens, cytotoxins, complement products, lipid products, and hypoxia. Activated endothelial cells exhibit new


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Histology_Ross. Folder 13.1). Inducers of endothelial activation include bacterial and viral antigens, cytotoxins, complement products, lipid products, and hypoxia. Activated endothelial cells exhibit new surface adhesion molecules and produce different classes of cytokines, lymphokines, growth factors, and vasoconstrictor and vasodilator molecules, as well as molecules that control blood coagulation.


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Histology_Ross. Endothelial cells participate in the structural and functional integrity of the vascular wall. Endothelial cells are active participants in a variety of interactions between the blood and underlying connective tissue and are responsible for many properties of the vessels (Table 13.2). These properties include the following.


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Histology_Ross.  The maintenance of a selective permeability barrier allows selective movement of small and large molecules from the blood to the tissues and from the tissues to the blood. This movement is related to the size and charge of the molecules. The endothelium is permeable to small hydrophobic (lipid-soluble) molecules (e.g., oxygen, carbon dioxide) that readily pass through the lipid bilayer of the endothelial cell membrane (a process called simple diffusion). However, water and hydrophilic (water-soluble) molecules (e.g., glucose, amino acids, electrolytes) cannot diffuse across the endothelial cell membrane. These molecules and solutes must be either actively transported across the plasma membrane and released into the extracellular space (transcellular pathways) or transported across the zonula occludens between two epithelial cells (paracellular pathway; see Chapter 5, Epithelial Tissue, page 125). The transcellular pathway uses numerous small pinocytotic vesicles (a


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Histology_Ross. across the zonula occludens between two epithelial cells (paracellular pathway; see Chapter 5, Epithelial Tissue, page 125). The transcellular pathway uses numerous small pinocytotic vesicles (a clathrin-independent form of endocytosis) to transport bulk material from the blood into the cell. In addition, some specific molecules (e.g., LDL, cholesterol, transferrin) are transported via receptor-mediated endocytosis (a clathrin-dependent process), which uses endothelial-specific surface receptors. In some blood vessels, larger molecules are transported through fenestrations within the endothelial cells visible in transmission electron microscope (TEM) preparations.


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Histology_Ross.  The maintenance of a nonthrombogenic barrier between blood platelets and subendothelial tissue is done by producing anticoagulants (agents that prevent coagulation such as thrombomodulin and others) and antithrombogenic substances (agents that prevent or interfere with platelet aggregation and release of factors that cause formation of clots, or thrombi, such as prostacyclin [PGI2] and tissue plasminogen activator). Normal endothelium does not support the adherence of platelets or the formation of thrombi on its surface. Damage to endothelial cells causes them to release prothrombogenic agents (agents that promote thombi formation) such as von Willebrand factor or plasminogen-activator inhibitor.


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Histology_Ross.  The modulation of blood ﬂow and vascular resistance is achieved by the secretion of vasoconstrictors (endothelins, angiotensin-converting enzyme [ACE], prostaglandin H2, thromboxane A2) and vasodilators (nitrous oxide [NO], prostacyclin). This subject is discussed in more depth in the next section.  The regulation and modulation of immune responses is done by controlling the interaction of lymphocytes with the endothelial surface, which is mainly achieved through the expression of adhesion molecules and their receptors on the endothelial-free surface as well as by secretion of three classes of interleukins (IL-1, IL-6, and IL-8).


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Histology_Ross.  Hormonal synthesis and other metabolic activities are done by the synthesis and secretion of various growth factors—for example, hemopoietic colony-stimulating factors (CSFs) such as granulocyte–macrophage CSF (GM-CSF), granulocyte CSF (G-CSF), and macrophage CSF (M-CSF); fibroblast growth factor (FGF); and platelet-derived growth factor (PDGF). Endothelial cells also synthesize growth inhibitors such as heparin and


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Histology_Ross. TABLE Characteristics of Blood Vessels 13.1 Arteries Vessel Diameter Tunica intima (inner layer) Tunica media (middle layer) Tunica adventitia (outer layer) Large artery (elastic artery) >10 mm Endothelium Connective tissue Smooth muscle Smooth muscle Elastic lamellae Connective tissue Elastic fibers Thinner than tunica media Medium artery (muscular artery) 2–10 mm Endothelium Connective tissue Smooth muscle Prominent internal elastic membrane Smooth muscle Collagen fibers Relatively little elastic tissue Connective tissue Some elastic fibers Thinner than tunica media Small artery 0.1–2 mm Endothelium Connective tissue Smooth muscle Internal elastic membrane Smooth muscle (8–10 cell layers) Collagen fibers Connective tissue Some elastic fibers Thinner than tunica media Arteriole 10–100 µm Endothelium Connective tissue Smooth muscle Smooth muscle (1–2 cell layers) Thin, ill-defined sheath of connective tissue Capillary 4–10 µm Endothelium None None Veins Vessel Diameter Tunica intima


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Histology_Ross. Endothelium Connective tissue Smooth muscle Smooth muscle (1–2 cell layers) Thin, ill-defined sheath of connective tissue Capillary 4–10 µm Endothelium None None Veins Vessel Diameter Tunica intima (inner layer) Tunica media (middle layer) Tunica adventitia (outer layer) Postcapillary venule 10–50 µm Endothelium Pericytes None None Muscular venule 50–100 µm Endothelium Smooth muscle (1–2 cell layers) Connective tissue Some elastic fibers Thicker than tunica media Small vein 0.1–1 mm Endothelium Connective tissue Smooth muscle (2–3 layers) Smooth muscle (2–3 layers continuous with tunica intima) Connective tissue Some elastic fibers Thicker than tunica media Medium vein 1–10 mm Endothelium Connective tissue Smooth muscle Internal elastic membrane in some cases Smooth muscle Collagen fibers Connective tissue Some elastic fibers Thicker than tunica media Large vein 10 mm Endothelium Connective tissue Smooth muscle Smooth muscle (2–15 layers) Cardiac muscle near heart Collagen fibers


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Histology_Ross. Connective tissue Some elastic fibers Thicker than tunica media Large vein 10 mm Endothelium Connective tissue Smooth muscle Smooth muscle (2–15 layers) Cardiac muscle near heart Collagen fibers Connective tissue Some elastic fibers, longitudinal smooth muscles Much thicker than tunica media transforming growth factor (TGF-). Endothelial cells function in the conversion of angiotensin I to angiotensin II in the renin–angiotensin system that controls blood pressure, as well as in the inactivation or conversion of a several compounds conveyed in the blood (norepinephrine, thrombin, prostaglandins, bradykinin, and serotonin) to inactive forms.


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Histology_Ross.  Modification of the lipoproteins occurs by oxidation. Lipoproteins, mainly LDLs with a high cholesterol content and very low-density lipoproteins (VLDLs), are oxidized by chapter 13 Cardiovascular System GENERAL FEATURES OF ARTERIES AND VEINS 411 Atherosclerotic lesions are the most common acquired abnormality of blood vessels. More than half of the annual deaths in the United States are related to complications of atherosclerotic disease, which includes ischemic heart disease (see Folder 13.3), myocardial infarction, stroke, and gangrene of the limbs. Lesions develop pri-marily in the tunica intima of large elastic arteries follow-ing endothelial injury, which leads to endothelial dysfunction. Factors that predispose to endothelial in-juries include low-LDL cholesterol hyperlipidemia, hyper-glycemia (in diabetes), hypertension, increased toxin levels associated with cigarette smoking, and certain viral and bacterial infections caused by cytomegalovirus (CMV) or Chlamydia


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Histology_Ross. hyper-glycemia (in diabetes), hypertension, increased toxin levels associated with cigarette smoking, and certain viral and bacterial infections caused by cytomegalovirus (CMV) or Chlamydia pneumoniae, respectively. Altered function of vascular endothelium leads to increased per-meability to LDL cholesterol and increased adherence of white blood cells to the endothelium. Endothelial injury in-creases the production of reactive oxygen species such as O2 , H2O2, OH, and ONOO, which in turn oxidize LDL in the tunica intima of the artery. In response to this injury, monocytes from the bloodstream enter the tunica intima and differentiate into macrophages. Macrophages phagocytize oxidized LDL, slowly transforming themselves into foam cells with a characteristic spongy appearance of the cytoplasm loaded with lipid-containing vesicles. Foam cells and infiltrated T lymphocytes form the initial atherosclerotic lesion, or fatty streak. This lesion under-goes further remodeling and growth into


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Histology_Ross. loaded with lipid-containing vesicles. Foam cells and infiltrated T lymphocytes form the initial atherosclerotic lesion, or fatty streak. This lesion under-goes further remodeling and growth into fibrofatty plaque as smooth muscle cells migrate from the media and fibrob-lasts form a protective capsule of connective tissue (Fig. F13.1.1). A thick layer of fibrous connective tissue con-taining scattered smooth muscle cells, macrophages, foam cells, T lymphocytes, cholesterol crystals, and cell debris is known as an atheromatous plaque. Progression of the plaque is marked by accumulation of lipid and loss of integrity of the endothelium. In advanced lesions, blood stasis and clotting (thrombosis) may lead to occlusion of the vessel. Other changes seen in advanced lesions in-clude thinning of the tunica media, calcification of accu-mulated extracellular lipids, and necrosis within the lesion (Fig. F13.1.2ab). Progression from simple to complicated lesions can be found in some people as


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Histology_Ross. of the tunica media, calcification of accu-mulated extracellular lipids, and necrosis within the lesion (Fig. F13.1.2ab). Progression from simple to complicated lesions can be found in some people as early as their 20s and in most individuals by age 50 or 60 years.


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Histology_Ross.  FOLDER 13.1 Clinical Correlation: Atherosclerosis


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Histology_Ross. FIGURE F13.1.1 • Schematic diagram of cellular interactions in the formation of an atheromatous plaque. Endothelial cells express cell adhesion molecules that initiate monocyte migration through the endothelium. Platelet-derived growth factor (PDGF) and other growth factors (blue arrow) released from endothelial cells stimulate migration of the smooth muscle cells from the tunica media to the tunica intima. In the tunica intima, smooth muscle cells produce large amounts of extracellular matrix (proteoglycans, collagen) that increase the thickness of the tunica intima. Foam cells derived from both macrophages and smooth muscle cells accumulate LDLs, which cross the endothelial barrier (yellow arrows) and are oxidized by free radicals produced by the endothelial cells. lumen lipid uptake cell adhesion molecules endothelium tunicaintimainternal elastic membrane tunicamediamonocyte smooth muscle cells cytokines oxidized LDL foam cells LDL LDL PDGF continued next page free radicals


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Histology_Ross. cell adhesion molecules endothelium tunicaintimainternal elastic membrane tunicamediamonocyte smooth muscle cells cytokines oxidized LDL foam cells LDL LDL PDGF continued next page free radicals produced by endothelial cells. Modified LDLs, in turn, are rapidly endocytosed by macrophages to form foam cells (see Fig. F13.1.1). Foam cells are a characteristic feature in the formation of atheromatous plaques.


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Histology_Ross. Endothelium of blood vessels controls contraction and relaxation of smooth muscle cells in the tunica media influencing local blood flow and pressure. The endothelial-derived relaxing factor (EDRF) was historically one of the early compounds discovered in the endothelial cells that was causing relaxation of blood vessels. For years, researchers had difficulty characterizing EDRF chemically. It is now known that most of the vascular effects of EDRF can be attributed to nitric oxide (NO) and its related compounds, which are released by endothelial cells in arteries, blood capillaries, and even lymphatic capillaries. As a chemical compound, NO is a gas with a very short physiologic half-life measured in seconds; hence, the difficulty with its discovery. Shear stress produced during the interaction of blood flow with vascular endothelial cells initiates nitric oxide (NO)-derived relaxation of blood vessels.


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Histology_Ross. Vasodilation (the relaxation of smooth muscle cells) increases the luminal diameter of the vessels, decreasing vascular resistance and systemic blood pressure. Endotheliumderived nitric oxide (NO) is one of several critical regulators of cardiovascular homeostasis. It regulates the blood vessel diameter, inhibits monocyte adhesion to dysfunctional endothelial cells, and maintains an antiproliferative and anti-apoptotic environment in the vessel wall. NO is an endogenous vasodilatory gas continuously synthesized in endothelial cells by endothelial nitric oxide synthase (eNOS). This Ca2-dependent enzyme catalyzes oxidation of L-arginine and acts through the G-protein–signaling cascade. Endothelial cells are constantly subjected to shear stress, the dragging force generated by the blood flow. Shear stress increases synthesis of a potent eNOS stimulator, the vascular endothelial growth factor (VEGF), and triggers a variety of other molecular and physical changes in endothelial cell


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Histology_Ross. flow. Shear stress increases synthesis of a potent eNOS stimulator, the vascular endothelial growth factor (VEGF), and triggers a variety of other molecular and physical changes in endothelial cell structure and function. Once NO is produced by endothelial cells, it diffuses out through the cell and basement membrane to the underlying tunica media and binds to guanylate cyclase in smooth muscle cytoplasm. This enzyme increases production of cGMP, which activates smooth muscle protein kinase G (PKG). Activation of protein kinase G has a negative effect on intracellular concentration of Ca2, causing smooth muscle relaxation (Fig 13.12). Note that NO is also a signaling molecule in many pathologic and physiologic processes.


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Histology_Ross. TABLE Summary of Endothelial Cell Properties and Functions 13.2 Major Properties Associated Functions Active Molecules Involved Maintenance of selective permeability barrier Simple diffusion Active transport Pinocytosis Receptor-mediated endocytosis Oxygen, carbon dioxide Glucose, amino acids, electrolytes Water, small molecules, soluble proteins LDL, cholesterol, transferrin, growth factors, antibodies, MHC complexes Maintenance of nonthrombogenic barrier Secretion of anticoagulants Secretion of antithrombogenic agents Secretion of prothrombogenic agents Thrombomodulin Prostacyclin (PGI2), tissue plasminogen activator (TPA), antithrombin III, heparin Tissue thromboplastin, von Willebrand factor, plasminogenactivator inhibitor Modulation of blood flow and vascular resistance Secretion of vasoconstrictors Secretion of vasodilators Endothelin, angiotensin-converting enzyme (ACE) Endothelial-derived relaxation factor (EDRF)/nitric oxide (NO), prostacyclin Regulation of cell growth


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Histology_Ross. of vasoconstrictors Secretion of vasodilators Endothelin, angiotensin-converting enzyme (ACE) Endothelial-derived relaxation factor (EDRF)/nitric oxide (NO), prostacyclin Regulation of cell growth Secretion of growth-stimulating factors Secretion of growth-inhibiting factors Platelet-derived growth factor (PDGF), hemopoietic colony-stimulating factors (GM-CSF, G-CSF, M-CSF) Heparin, transforming growth factor (TGF-) Regulation of immune responses Regulation of leukocyte migration by expression of adhesion molecules Regulation of immune functions Selectins, integrins, CD marker molecules Interleukin molecules (IL-1, IL-6, IL-8), MHC molecules Maintenance of extracellular matrix Synthesis of basal lamina Synthesis of glycocalyx Type IV collagen, laminin Proteoglycans Involvement in lipoprotein, cholesterol, metabolism Production of free radicals Oxidation of LDL Reactive oxygen species (ROS), LDL, VLDL Modified from Cotran S, Kumar V, Collins T, Robbins SL, eds. Robbins Pathologic


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Histology_Ross. cholesterol, metabolism Production of free radicals Oxidation of LDL Reactive oxygen species (ROS), LDL, VLDL Modified from Cotran S, Kumar V, Collins T, Robbins SL, eds. Robbins Pathologic Basis of Disease. Philadelphia: WB Saunders, 1999.


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Histology_Ross. It acts as an anti-inflammatory agent under normal physiologic conditions, although its overproduction induces inflammation. NO is also involved in immune reactions (it stimulates macrophages to release high concentrations of NO), is a potent neurotransmitter in the nervous system, and contributes to the regulation of apoptosis. The pathogenesis of inflammatory disorders of the joint, gut, and lungs is linked to local overproduction of NO. Recently, NO inhibitors have been used to manage inflammatory diseases.


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Histology_Ross. Metabolic stress in endothelial cells also contributes to smooth muscle relaxation. Endothelium-derived relaxing factors include prostacyclin (PGI2), which in addition to relaxing smooth muscles is a potent inhibitor of platelet aggregation. PGI2 binds to receptors on the smooth muscles; stimulates cAMP-activated protein kinase A (PKA), which in turn phosphylates myosin light chain kinase (MLCK); and prevents activation of the calcium– calmodulin complex. This type of relaxation occurs without change in the intracellular Ca2 concentration. represents another endothelium-derived relaxing factor that acts on Ca2-dependent potassium channels causing hyperpolarization of smooth muscle cells and their relaxation (see Fig 13.12). Endothelins produced by vascular endothelial cells play an important role in both physiologic and pathologic mechanisms of the circulatory system.


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Histology_Ross. Endothelins produced by vascular endothelial cells play an important role in both physiologic and pathologic mechanisms of the circulatory system. Vasoconstriction (contraction of smooth muscle) in the tunica media of small arteries and arterioles reduces the luminal diameter of these vessels and increases vascular resistance. Vasoconstriction increases systemic blood pressure. In the past, vasoconstriction was thought to be mainly induced by nerve impulses or circulating hormones. Today it is known that endothelium-derived factors play an important role in both physiologic and pathologic mechanisms of the circulatory system. Members of the endothelin


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Histology_Ross. FIGURE 13.12 • Molecular mechanism of blood vessel vasodilatation. Relaxation of smooth muscle cells in the wall of the blood vessel causes an increase of its diameter and decreases in vascular resistance and systemic blood pressure. Nitric oxide (NO) produced by the endothelial nitric oxide synthase (eNOS) in endothelial cells is an important molecule regulating relaxation of vascular smooth muscles. Other molecules include ADP, vascular endothelial growth factor (VEGF ), bradykinin, prostacyclin (PGI2), and endothelium-derived hyperpolarizing factor (EDHF ). Shear stress produced between erythrocytes and endothelial cells as well as VEGF activate eNOS, increasing the production of NO. Once NO is produced, it diffuses to the underlying smooth muscles and activates guanylate cyclase production of cGMP, which in turn activates cGMP-dependent protein kinase G (PKG) metabolic pathways, causing smooth muscle relaxation. Metabolic stress of endothelial cells caused by increased levels of


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Histology_Ross. of cGMP, which in turn activates cGMP-dependent protein kinase G (PKG) metabolic pathways, causing smooth muscle relaxation. Metabolic stress of endothelial cells caused by increased levels of ADP or PGI2 stimulates cAMP-activated protein kinase A (PKA) metabolic pathways in smooth muscles, causing their relaxation. In addition, EDHF opens the potassium channels, causing hyperpolarization of smooth muscle cell membranes, further leading to their relaxation. (Based on Noble A, Johnson R, Thomas A, Bass P. The Cardiovascular System. London, New York: Churchill Livingstone, 2005.) family of 21 amino acid peptides produced by vascular endothelial cells are the most potent vasoconstrictors. The family consists of three members: endothelin-1 (ET-1), endothelin-2 (ET-2), and endothelin-3 (ET-3). Endothelins act mainly as paracrine and autocrine agents and bind to their own receptors on the epithelial cells and vascular smooth muscles (Fig 13.13). The ET-1 is the most potent naturally


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Histology_Ross. (ET-3). Endothelins act mainly as paracrine and autocrine agents and bind to their own receptors on the epithelial cells and vascular smooth muscles (Fig 13.13). The ET-1 is the most potent naturally occurring vasoconstricting agent that interacts with its ETA receptor on vascular smooth muscles.


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Histology_Ross. High levels of ET-1 gene expression are associated with many diseases that are caused in part by sustained en-dothelium-induced vasoconstriction. These include systemic hypertension (see Folder 13.2), pulmonary hypertension, atherosclerosis, congestive heart failure, idiopathic cardiomyopathy, and renal failure. It is interesting to mention that snake venom from the Israeli burrowing asp (Atractaspis engaddensis) contains sarafotoxin, a highly toxic protein that exhibits a very high degree of sequence homology with ET-1. After it enters the circulation, it binds to ETA receptors and causes life-threatening, intense coronary vasoconstriction. This is remarkable because endothelin is a natural compound of the human vascular system, whereas sarafotoxin is a toxin in the snake venom. The other endothelium-derived vasoconstrictors include thromboxane A2 and prostaglandin


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Histology_Ross. H2. Thromboxane A2 is synthesized from prostaglandin H2. In addition, decreased rate of NO production or inactivation of NO by the superoxide anion (O2–) has a stimulating effect on smooth muscle contraction (see Fig. 13.13). Traditionally, arteries are classified into three types on the basis of size and the characteristics of the tunica media.  Large arteries or elastic arteries such as the aorta and pulmonary arteries convey blood from the heart to the systemic and pulmonary circulations, respectively (see Fig. 13.2). Their main branches—the brachiocephalic trunk, common carotid, subclavian, and common iliac arteries—are also classified as elastic arteries.  Medium arteries or muscular arteries (most of the “named” arteries of the body) cannot be sharply distinguished from elastic arteries. Some of these arteries are difficult to classify because they have features that are intermediate between the two types.


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Histology_Ross.  Small arteries and arterioles are distinguished from one another by the number of smooth muscle layers in the tunica media. By definition, arterioles have only one or two


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Histology_Ross. FIGURE 13.13 • Molecular mechanism of blood vessel vasoconstriction. Contraction of vascular smooth muscle in a blood vessel (vasoconstriction) decreases its diameter and increases vascular resistance, leading to increased systemic blood pressure. Binding of angiotensin II and thrombin to vascular endothelial cells stimulate synthesis of endothelium-derived factors that regulate smooth muscle contraction. These include endothelins (the most potent family of vasoconstrictors), prostaglandin H2 (PGH2), and its derivative thromboxane A2. They bind to their own receptors on the smooth muscle cell membrane, causing an influx of Ca2 and an increase in the release of intracellular-stored Ca2 from the sarcoplasmic reticulum. The reduced rate of nitric oxide (NO) production, which is a potent vasodilatator, or inactivation of NO by the superoxide anion (O2–) has a stimulating effect on smooth muscle contraction. (Based on Noble A, Johnson R, Thomas A, Bass P. The Cardiovascular System. London,


Histology_Ross

Histology_Ross. or inactivation of NO by the superoxide anion (O2–) has a stimulating effect on smooth muscle contraction. (Based on Noble A, Johnson R, Thomas A, Bass P. The Cardiovascular System. London, New York: Churchill Livingstone, 2005.) layers, and small arteries may have as many as eight layers of smooth muscle in their tunica media.


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Histology_Ross. Elastic arteries have multiple sheets of elastic lamellae in their walls.


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Histology_Ross. From a functional standpoint, elastic arteries serve primarily as conduction tubes; however, they also facilitate the continuous and uniform movement of blood along the tube. Blood flow occurs as follows: The ventricles of the heart pump blood into the elastic arteries during systole (the contraction phase of the cardiac cycle). The pressure generated by contraction of the ventricles moves the blood through the elastic arteries and along the arterial tree. Simultaneously, it also causes the wall of the large elastic arteries to distend. The distension is limited by the network of collagenous fibers in the tunica media and tunica adventitia (Fig. 13.14). During diastole (the relaxation phase of the cardiac cycle), when no pressure is generated by the heart, the recoil of the distended elastic arteries serves to maintain arterial blood pressure and the flow of blood within the vessels. Initial elastic recoil forces blood both away from and back toward the heart. The flow of blood toward


Histology_Ross

Histology_Ross. arteries serves to maintain arterial blood pressure and the flow of blood within the vessels. Initial elastic recoil forces blood both away from and back toward the heart. The flow of blood toward the heart causes the aortic and pulmonary valves to close. Continued elastic recoil then maintains continuous flow of blood away from the heart.


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Histology_Ross. The tunica intima of the elastic artery consists of endothelium, subendothelial connective tissue, and an inconspicuous internal elastic membrane. The tunica intima of elastic arteries is relatively thick and consists of the following.


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Histology_Ross.  In the endothelial lining with its basal lamina, the cells are typically flat and elongated, with their long axes oriented parallel to the direction of blood flow in the artery (Fig. 13.15). In forming the epithelial sheet, the cells are joined by tight junctions (zonulae occludentes) and gap junctions (Fig. 13.16). Endothelial cells possess rodlike inclusions called Weibel-Palade bodies that are present in the cytoplasm. These specific endothelial organelles are electron-dense structures and contain von Willebrand factor and P-selectin. Von Willebrand factor is a glycoprotein synthesized by arterial endothelial cells. When secreted into the blood, it binds coagulating factor VIII) and plays an important role in platelets’ adhesion to the site of endothelial injury. The antibody to von Willebrand factor is commonly used as an immunohistochemical marker for identification of en-dothelium-derived tumors. P-selectin is a cell adhesion molecule involved in the mechanism of neutrophil–


Histology_Ross

Histology_Ross. Willebrand factor is commonly used as an immunohistochemical marker for identification of en-dothelium-derived tumors. P-selectin is a cell adhesion molecule involved in the mechanism of neutrophil– endothelial cell recognition. It initiates neutrophil migration from the blood to the site of action in the connective tissue.


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Histology_Ross.  FOLDER 13.2 Clinical Correlation: Hypertension


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Histology_Ross. Hypertension, or high blood pressure, occurs in about 25% of the population and is defined by a sustained dias-tolic pressure greater than 90 mmHg or a sustained systolic pressure greater than 140 mmHg. Hypertension is often as-sociated with atherosclerotic vascular disease and with an increased risk of cardiovascular disorders such as stroke and angina pectoris. In most cases of hypertension, the luminal diameter of small muscular arteries and arterioles is reduced, which leads to increased vascular resistance. Re-striction in the luminal size may also result from active con-traction of smooth muscle in the vessel wall, an increase in the amount of smooth muscle in the wall, or both. In individuals with hypertension, smooth muscle cells multiply. The additional smooth muscle then adds to the thickness of the tunica media. Concomitantly, some of the smooth muscle cells accumulate lipid. This is one reason why hypertension is a major risk factor for atherosclerosis. In fat-fed animals,


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Histology_Ross. the thickness of the tunica media. Concomitantly, some of the smooth muscle cells accumulate lipid. This is one reason why hypertension is a major risk factor for atherosclerosis. In fat-fed animals, hypertension accelerates the rate of lipid accumulation in vessel walls. In the absence of a fatty diet, hypertension increases the rate of intimal thickening that occurs naturally with age. Cardiac muscle is also affected by chronic hypertension that leads to pressure overload, resulting in compensatory left ventricular hypertrophy. Ventricular hypertrophy in this condition is caused by an increased diameter (not length) of cardiac muscle cells with characteristic enlarged and rectangular nuclei. Left ventricular hypertrophy is a com-mon manifestation of the hypertensive heart disease. Ventricular hypertrophy makes the wall of the left ventricle uniformly much thicker and less elastic, and the heart must then work harder to pump blood (Fig. F13.2.1). Untreated hypertensive heart disease


Histology_Ross

Histology_Ross. hypertrophy makes the wall of the left ventricle uniformly much thicker and less elastic, and the heart must then work harder to pump blood (Fig. F13.2.1). Untreated hypertensive heart disease would lead to cardiac failure. Recent studies have shown that prolonged reduction of blood pressure in patients with ventricular hypertrophy as a result of chronic hypertension can reduce the degree of hypertrophy. normal wall of right ventricle hypertrophied wall of left ventricle FIGURE F13.2.1 • Horizontal section of the heart with left ventricular hypertrophy. This photograph shows a cross section of the ventricles of the heart from a patient with chronic hypertension. The walls of the left ventricle are concentrically thickened, resulting in decreases of the cavity diameter. Note the wall of the right ventricle, which has normal dimensions. (Reprinted with permission from Rubin R, Strayer DS. Rubin’s Pathology. 5th ed. Baltimore: Lippincott Williams & Wilkins, 2008.)  The subendothelial


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Histology_Ross. the right ventricle, which has normal dimensions. (Reprinted with permission from Rubin R, Strayer DS. Rubin’s Pathology. 5th ed. Baltimore: Lippincott Williams & Wilkins, 2008.)  The subendothelial layer of connective tissue in larger elastic arteries consists of connective tissue with both collagen and elastic fibers. The main cell type in this layer is the smooth muscle cell. It is contractile and secretes extracellular ground substance as well as collagen and elastic fibers. Occasional macrophages may also be present.


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Histology_Ross.  The internal elastic membrane in elastic arteries is not conspicuous because it is one of many elastic layers in the wall of the vessel. It is usually identified only because it is the innermost elastic layer of the arterial wall. Endothelial cells participate in the structural and functional integrity of the vascular wall. Endothelial cells not only provide a physical barrier between the circulating blood and the subendothelial tissues but also produce vasoactive agents that cause constriction and relaxation of underlying vascular smooth muscles. Multiple roles and functions of the endothelium lining of blood vessels are described in detail at the beginning of this chapter (see page 409). The tunica media of elastic arteries consists of multiple layers of smooth muscle cells separated by elastic lamellae. The tunica media is the thickest of the three layers of elastic arteries and consists of the following.


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Histology_Ross. The tunica media is the thickest of the three layers of elastic arteries and consists of the following.  Elastin in the form of fenestrated sheets or lamellae between the muscle cell layers. These lamellae are arranged in concentric layers (Figs. 13.17a, 13.14, and Plate 33, page 434). As noted, fenestrations in the lamellae facilitate the diffusion of substances within the arterial wall. The number and thickness of these lamellae are related to blood pressure and age. At birth, the aorta is almost devoid of lamellae; in the adult, the aorta has 40 to 70 lamellae. In individuals with hypertension, both the number and the thickness of the lamellae are increased.


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Histology_Ross. FIGURE 13.14 • Diagram and photomicrograph of an elastic artery. a. This schematic diagram of a typical elastic artery shows its cellular and extracellular components. Note the organization of smooth muscle cells in the tunica media and the distribution of elastic lamellae. The internal elastic membrane is not well defined and is represented by the innermost elastic lamellae of the arterial wall. b. This low magnification photomicrograph shows the section of the wall of the human aorta stained with Weigert’s resorcin-fuchsin elastic stain to visualize elastic lamellae interspersed with the smooth muscle cells of the tunica media. Only the tunica media, which is the thickest of the three layers of the elastic arteries, is labeled on this image. Note that elastic lamellae, collagen fibrils, and blood vessels are present in the tunica adventitia. 48.


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Histology_Ross.  Smooth muscle cells are arranged in layers. The smooth muscle cells are arranged in a low-pitch spiral relative to the long axis of the vessel; thus, in cross sections of the artery they appear in a circular array. The smooth muscle cells are spindle-shaped with an elongated nucleus. They are invested with an external (basal) lamina except where they are joined by gap junctions. Fibroblasts are not present in the tunica media. Smooth muscle cells synthesize the collagen, elastin, and other molecules of the extracellular matrix. In addition, in response to growth factors (i.e., PDGF, FGF) produced by endothelial cells, smooth muscle cells may proliferate and migrate to the adjacent intima. This characteristic is important in normal repair of the vascular wall and in pathologic processes similar to those occurring in atherosclerosis.  Collagen fibers and ground substance (proteoglycans) are synthesized and secreted by the smooth muscle cells.


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Histology_Ross.  Collagen fibers and ground substance (proteoglycans) are synthesized and secreted by the smooth muscle cells. The tunica adventitia in the elastic artery is a relatively thin connective tissue layer. In elastic arteries, the tunica adventitia is usually less than half the thickness of the tunica media. It consists of the following.  Collagen fibers and elastic fibers form a loose network of elastic fibers (not lamellae) that are less organized than those in the tunica media. The collagen fibers help prevent the expansion of the arterial wall beyond physiologic limits during systole of the cardiac cycle.  Fibroblasts and macrophages are the principal cells of the tunica adventitia.


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Histology_Ross.  Fibroblasts and macrophages are the principal cells of the tunica adventitia.  The vasa vasorum (blood vessels) and nervi vascularis (nerves) include arterial branches and veins similar to that of vasculature in general and provide nutrients and remove waste products from the outer portion of the arterial wall. They may partially enter the outer part of the tunica media. The inner part of the wall is supplied by nutrients from the lumen of the vessel. The hemodynamic impact (i.e., increased blood pressure) on the function of the vasa vasorum may play a role in the pathogenesis of atheromatous plaques. Muscular arteries have more smooth muscle and less elastin in the tunica media than do elastic arteries.


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Histology_Ross. Muscular arteries have more smooth muscle and less elastin in the tunica media than do elastic arteries. Generally, in the region of transition between elastic arteries and large muscular arteries, the amount of elastic material decreases, and smooth muscle cells become the predominant endothelial cells cytoplasm of endothelial cells basal lamina junctional complex ba FIGURE 13.15 • Diagram and scanning electron micrograph of the endothelium. a. This schematic drawing shows the luminal surface of the endothelium. The cells are elongated with their long axis parallel to the direction of blood flow. Nuclei of endothelial cells are also elongated in the direction of blood flow. b. Scanning electron micrograph of a small vein, showing the cells of the endothelial lining. Note the spindle shape with the long axis of the cells running parallel to the vessel. 1,100.


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Histology_Ross. FIGURE 13.16 • Diagram depicting segments of two adjacent endothelial cells. This diagram shows cell-to-cell and cellto-extracellular matrix junctions in the endothelial cells. Junctional complex near the luminal surface (dashed line box) comprises the zonula occludens and the zonula adherens, and a desmosome represents a group of cell-to-cell junctions that maintain selective permeability barrier. Cell-to-cell communication junctions are represented by an area of gap junctions (green). Anchoring junctions (cell-to-extracellular matrix) are represented here by hemidesmosomes and focal adhesions. Observe the organization of the cytoplasm and cytoplasmic inclusions, the Weibel-Palade bodies, that are characteristic of endothelial cells. Pinocytotic vesicles in the cell on the left have been positioned to suggest the pathway of vesicles from the lumen of the blood vessel to the basal cell membrane or to the lateral cell membrane as indicated by the dashed arrows. Various markers have


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Histology_Ross. positioned to suggest the pathway of vesicles from the lumen of the blood vessel to the basal cell membrane or to the lateral cell membrane as indicated by the dashed arrows. Various markers have been traced through pinocytotic pathways across the endothelial cell. Luminal surface of the endothelial cells expresses variety of endothelial cell-surface receptors.


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Histology_Ross. FIGURE 13.17 • Photomicrographs of the wall of elastic and muscular types of arteries. a. This photomicrograph shows a cross section of the human aorta stained with resorcin-fuchsin to demonstrate elastic material. Three layers can be recognized: the tunica intima, the tunica media, and the tunica adventitia. The tunica intima consists of a lining of endothelial cells that rest on a thin layer of connective tissue containing smooth muscle cells, occasional macrophages, and collagen and elastic fibers. The boundary between it and the tissue below, the tunica media, is not sharply defined. The tunica media contains an abundance of smooth muscle cells (note the blue-staining nuclei) and numerous elastic fenestrated membranes (the red, wavy lamellae). The tunica adventitia, the outermost part, lacks elastic laminae, consists mainly of connective tissue, and contains the blood vessels and nerves that supply the aortic wall. 300. b. Photomicrograph of a cross section through a muscular


Histology_Ross

Histology_Ross. part, lacks elastic laminae, consists mainly of connective tissue, and contains the blood vessels and nerves that supply the aortic wall. 300. b. Photomicrograph of a cross section through a muscular artery in a routine H&E preparation shows that the wall of the muscular artery is also divided into the same three layers as in the elastic artery. The tunica intima consists of an endothelial lining, a small amount of connective tissue, and the internal elastic membrane. This structure has a scalloped appearance when the vessel is constricted and is highly refractile. Constriction also causes the endothelial cell nuclei to appear rounded. The tunica media consists mainly of circularly arranged smooth muscle cells and collagen and elastic fibers. The nuclei of the smooth muscle cells, when contracted, have a corkscrew appearance. The tunica adventitia consists mostly of connective tissue. A well-defined external elastic membrane is not apparent in this vessel, but profiles of elastic


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Histology_Ross. contracted, have a corkscrew appearance. The tunica adventitia consists mostly of connective tissue. A well-defined external elastic membrane is not apparent in this vessel, but profiles of elastic material (arrows) are present. 360.


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Histology_Ross. constituent of the tunica media (Fig. 13.18 and Plate 34, page 436). Also, a prominent internal elastic membrane becomes apparent, helping to distinguish muscular arteries from elastic arteries. In many instances, a recognizable external elastic membrane is also evident. The tunica intima is thinner in muscular arteries and contains a prominent internal elastic membrane. The tunica intima is relatively thinner in muscular arteries than in elastic arteries and consists of an endothelial lining with its basal lamina, a sparse subendothelial layer of connective tissue, and a prominent internal elastic membrane. In some muscular arteries, the subendothelial layer is so scanty that the basal lamina of the endothelium appears to make contact with the internal elastic membrane. In histologic sections, the internal elastic membrane usually appears as a well-defined, undulating or wavy structure because of contraction of the smooth muscle (Fig. 13.17b).


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Histology_Ross. The thickness of the tunica intima varies with age and other factors. In young children, it is very thin. In muscular arteries of young adults, the tunica intima accounts for about one-sixth of the total wall thickness. In older adults, the tunica intima may be expanded by lipid deposits, often in the form of irregular “fatty streaks.” The tunica media of muscular arteries is composed almost entirely of smooth muscle, with little elastic material. The tunica media of muscular arteries consists of smooth muscle cells amid collagen fibers and relatively little elastic material. The smooth muscle cells are arranged in a spiral fashion in the arterial wall. Their contraction helps maintain blood pressure. As in elastic arteries, there are no fibroblasts in this layer. The smooth muscle cells possess an external (basal) lamina except at the sites of gap junctions and produce extracellular collagen, elastin, and ground substance.


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Histology_Ross. FIGURE 13.18 • Diagram and photomicrograph of a muscular artery. a. In this schematic diagram of a muscular artery, the cellular and extracellular components are labeled. Note the distribution of cellular components in all three tunics and the locations of external and internal elastic membranes. b. In this photomicrograph of a cross section through a muscular artery in Weigert’s resorcin-fuchsin elastic stain preparation, note two distinct layers of elastic tissue: a wavy-appearing inner layer of the internal elastic membrane and a well-defined outer layer of the external elastic membrane. The relatively thick tunica media enclosed by the internal and external elastic membranes consists mainly of circularly arranged smooth muscle cells, collagen, and fine elastic fibers. The tunica intima in this preparation is indiscernible; the tunica adventitia is well defined, consisting mostly of connective tissue with collagen and elastic fibers. 175.


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Histology_Ross. The tunica adventitia of muscular arteries is relatively thick and is often separated from the tunica media by a recognizable external elastic membrane. The tunica adventitia of muscular arteries consists of fibroblasts, collagen fibers, elastic fibers, and, in some vessels, scattered adipose cells. Compared with elastic arteries, the tunica adventitia of muscular arteries is relatively thick—about the same thickness as the tunica media. Collagen fibers are the principal extracellular component. However, a concentration of elastic material immediately adjacent to the tunica media is often present and as such constitutes the external elastic membrane. Nerves and small vessels travel in the adventitia and give off branches that penetrate into the tunica media in the large muscular arteries as the vasa vasorum. Small arteries and arterioles are distinguished from one another by the number of smooth muscle cell layers in the tunica media.


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Histology_Ross. Small arteries and arterioles are distinguished from one another by the number of smooth muscle cell layers in the tunica media. As mentioned previously, arterioles have only one or two layers, and a small artery may have as many as eight layers of smooth muscle in the tunica media (Fig. 13.19) and (Plate 35, page 438). Typically, the tunica intima of a small artery has an internal elastic membrane, whereas this layer may or may not be present in the arteriole. The endothelium in both is essentially similar to endothelium in other arteries, except that at the electron microscope level, gap junctions may be found between endothelial cells and the smooth muscle cells of the tunica media. Last, the tunica adventitia is a thin, ill-defined sheath of connective tissue that blends with the connective tissue in which these vessels travel. Arterioles control blood flow to capillary networks by contraction of the smooth muscle cells.


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Histology_Ross. Arterioles control blood flow to capillary networks by contraction of the smooth muscle cells. Arterioles serve as flow regulators for the capillary beds. In the normal relationship between an arteriole and a capillary network, contraction of the smooth muscle in the wall of an arteriole increases the vascular resistance and reduces or shuts off the blood going to the capillaries. The slight thickening of the smooth muscle at the origin of a capillary bed from an arteriole is called the precapillary sphincter. Most arterioles can dilate 60% to 100% from their resting diameter, and they can maintain as much as 40% constriction for a long time. Therefore, a large decrease or increase in vascular resistance has a direct effect on distribution of blood flow and systemic arterial pressure. This regulation directs blood to where it may be most needed. For instance, during strenuous physical exertion such as running, blood


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Histology_Ross. FIGURE 13.19 • Electron micrograph and photomicrograph of arterioles. a. This electron micrograph shows a cross section of an arteriole. The tunica intima of the vessel is composed of an endothelium and a very thin layer of subendothelial connective tissue (collagen fibrils and ground substance). The arrows indicate the site of junction between adjoining endothelial cells. The tunica media consists of a single layer of smooth muscle cells (SM). The tunica adventitia is composed of collagen fibrils and several layers of fibroblasts (F) with extremely attenuated processes. Red blood cells are visible in the lumen. 6,000. b. Photomicrograph of arteriole and venule in the dermis. One arteriole is seen in longitudinal section, and another is seen in cross section. The round and ovoid nuclei in the wall of the longitudinally sectioned arteriole belong to the smooth muscle cells of the tunica media. Their round to ovoid shape indicates that these cells have been cut in cross section. The