Heart_Braun_Notes_2024-25.pdf

Microanatomy of the Heart Rod D. Braun Page 1 of 25 MICROANATOMY OF THE HEART 1. Describe the relationship of the pericardium to the rest of the heart. Define the layers...

Microanatomy of the Heart Rod D. Braun Page 1 of 25 MICROANATOMY OF THE HEART 1. Describe the relationship of the pericardium to the rest of the heart. Define the layers of the pericardium and describe their components. Describe the function of pericardial fluid. Describe the flow of blood through the heart. Describe the structures that separate the 4 chambers of the heart. 2. Describe the microanatomy and function of the cardiac skeleton. Describe the anatomical location and histological organization of the cardiac skeleton. Describe the components of the cardiac skeleton. Describe the functions of the cardiac skeleton. 3. Describe the microanatomy and functions of the layers of the heart wall Describe the relationship between the 3 tunics of blood vessels and the layers of the heart wall (epicardium, myocardium, and endocardium). Identify the layers of the heart wall at the LM level. Describe the content and arrangement of basic tissues found in the layers of the heart wall. Compare and contrast the features of the atrial and ventricular walls and distinguish between them at the LM level. Compare and contrast atrial and ventricular myocardial cells. Describe the production and effects of atrial natriuretic factor (ANF or ANP) and brain natriuretic peptide (BNP). 4. Describe the functional organization of the cardiac impulse conduction system beginning with the sinoatrial (SA) node and ending with ventricular myocardial cells. Describe the difference between SA and AV nodal cells and normal myocardial cells. Describe the location of Purkinje fibers in the heart wall and identify them in LM sections. Compare and contrast Purkinje fibers with normal cardiac muscle cells. 5. Describe the microanatomy and function of heart valves. Describe the histological organization of cardiac valves. Describe the relationship of cardiac valves with the papillary muscles and chordae tendineae. Identify papillary muscles and chordae tendineae in LM sections of the heart. Microanatomy of the Heart Rod D. Braun Page 2 of 25 Lecture Content Outline Cardiovascular system: Review I. Pericardium and heart A. Pericardium B. Chambers of the heart II. Cardiac skeleton A. General features B. Components C. Functions of cardiac skeleton III. Heart wall A. Epicardium B. Myocardium C. Endocardium IV. Impulse conduction system A. Characteristics B. Sinoatrial (SA) node C. Atrioventricular (AV) node D. Bundle of His (AV bundle) and left and right bundle branches E. Purkinje fibers V. Valves of the heart A. Four valves B. Structure C. Chordae tendineae Microanatomy of the Heart Rod D. Braun Page 3 of 25 MICROANATOMY OF THE HEART CARDIOVASCULAR SYSTEM: REVIEW A. COMPONENTS: heart, blood vessels, and lymphatic vessels. We will only be concerned here with the heart. B. CIRCULATIONS: Two circuits (circulations) distribute blood in the body (Figure 1). 1. Pulmonary circulation a. Deoxygenated blood is pumped from heart to lungs via the Figure 1. Schematic of cardiovascular system: heart and two pulmonary circulations (pulmonary and systemic). Modified from Human Histology: A Microfiche Atlas, Erlandsen & Magney (1985). artery. b. Oxygenated blood returns to heart via the pulmonary vein. 2. Systemic circulation a. Oxygenated blood is pumped from heart to other tissues via arteries. b. Nutrient exchange occurs in capillaries. c. Deoxygenated blood returns from tissues to heart via veins. Microanatomy of the Heart Rod D. Braun Page 4 of 25 C. TUNICS (LAYERS) OF BLOOD VESSELS: Recall that blood vessel walls can have three tunics or layers (Figure 2). The number of tunics and the cellular and extracellular components of the tunics will vary with the size and function of different blood vessels (see Vascular System lecture). Layers of the heart wall are analogous to the vessel tunics Figure 2. Vessel tunics. Modified from Graphic 8-1 from (see Section III). rd Color Atlas of Histology (Gartner & Hiatt, 3 ed., 2000). 1. Tunica intima a. Innermost layer of blood vessel wall. b. The tunica intima includes a single layer of squamous epithelial cells known as vascular endothelium. 2. Tunica media a. Middle layer of blood vessel wall. b. Depending on the type of vessel, the predominant element of the tunica media is either circumferentially arranged smooth muscle cells or elastic lamellae. c. The smooth muscle cells produce the extracellular molecules of the tunica media. Microanatomy of the Heart Rod D. Braun Page 5 of 25 3. Tunica adventitia a. Outermost connective tissue layer of vessel wall. b. It consists of longitudinally arranged collagen and elastic fibers, smooth muscle cells, and fibroblasts. c. It may contain vasa vasorum and nervi vascularis. Figure 3. Layers of the pericardium. Note reflexion at the base (top) of the heart, where the pericardium attaches to the heart wall. Also, note that the visceral layer of the serous pericardium is the same as the epicardium of the heart wall. The red box on the right shows the location of the histological section presented in Figure 4, and the blue box shows the location of the histological section presented in Figure 5. I. PERICARDIUM AND HEART The heart is located in the middle mediastinum and is surrounded by the pericardial sac (Figure 3, left). A. PERICARDIUM: 1. Pericardial sac (pericardium) has two layers (Figure 3): a. Fibrous pericardium (external fibrous layer): dense fibroelastic connective tissue (Figure 4, *) that blends in with surrounding loose connective tissue. Microanatomy of the Heart Rod D. Braun Page 6 of 25 b. Serous pericardium, which is further divided into two layers: i. Parietal layer of serous pericardium: loose connective tissue plus layer of squamous epithelium (mesothelium) (Figure 4, arrowhead). Figure 4. Parietal layer of serous pericardium Parietal layer is and fibrous pericardium (*). Pericardial cavity is at bottom. Arrowhead: mesothelium. The location of adjacent to the this histological section is indicated by the red box in the diagram shown in Figure 3. Modified fibrous pericardium from Visual Aids for Human Histology, Case (Figure 4, *). ii. Visceral layer of serous pericardium (Figure 5, bracketed): loose connective tissue plus layer of squamous epithelium (mesothelium). Figure 5. Visceral layer of serous pericardium or This layer is also epicardium (bracketed) and myocardium (bottom). Pericardial cavity (space) is at top of called the figure. Surface of visceral layer bordering the pericardial cavity is lined by mesothelium. The epicardium of the location of this histological section is indicated by the blue box in the diagram shown in Figure 3. Modified from Michigan Medical Histology heart wall. Microanatomy of the Heart Rod D. Braun Page 7 of 25 2. Parietal and visceral layers of the serous pericardium are continuous. a. The layers meet at the superior reflexion at the base of the heart (Figure 3). b. The two layers form the walls of the pericardial sac (cavity). 3. In between the parietal and visceral layers of the serous pericardium is the pericardial cavity (Figure 3). a. The pericardial cavity is actually a narrow space that is lubricated by a thin film of pericardial fluid. b. This space contains only several milliliters of pericardial fluid and functions to help lubricate the heart to prevent friction during beating. B. CHAMBERS OF THE HEART 1. The human heart consists of four chambers: right and left atria and right and left ventricles (Figures 6 and 7). 2. Path of blood flow in heart (Figure 7) a. Deoxygenated blood returns from the body tissues via the inferior and superior vena cava to the right atrium. b. It passes from the right atrium to the right ventricle via the tricuspid valve. Microanatomy of the Heart Rod D. Braun Page 8 of 25 Figure 6. Schematic showing chambers of the heart, interatrial septum, and interventricular septum. Components of impulse Figure 7. Chambers of the heart and path of blood conduction system also shown (Section IV). Modified from Figure flow. Figure 13-4 in Textbook of Medical Physiology th 13.5 in Histology: A Text and Atlas (Ross & Pawlina, 6 ed., 2011). th (Guyton, 6 ed., 1980). c. Blood is then pumped through the pulmonary semilunar valve to the pulmonary artery, which delivers the blood to the lungs, where it is oxygenated. d. Oxygenated blood returns to the left atrium of the heart via the pulmonary vein. e. Blood passes through the mitral or bicuspid valve to fill the left ventricle. f. Oxygenated blood is pumped from the left ventricle, through the aortic semilunar valve, into the aorta and the arterial tree. Microanatomy of the Heart Rod D. Braun Page 9 of 25 g. After flowing through the systemic circulation, blood returns to the right atrium via the veins. The cycle begins again. 3. The atria are separated by the interatrial septum, and the ventricles are separated by the interventricular septum (Figure 6). 4. The two atria and two ventricles are separated by the cardiac skeleton. II. CARDIAC SKELETON A. GENERAL FEATURES 1. The cardiac skeleton is the central supporting structure of the heart to which some of the cardiac muscle fibers are attached and Figure 8. Position and components of the cardiac skeleton. From Human with which the Histology: A Microfiche Atlas, Erlandsen & Magney (1985). valves are supported (Figure 8). 2. Structures of the cardiac skeleton are composed of dense irregular connective tissue. Microanatomy of the Heart Rod D. Braun Page 10 of 25 B. COMPONENTS (Figures 8 and 9) 1. Annuli fibrosi a. Ring of dense irregular connective tissue that surrounds each of the four cardiac valves to stabilize them. Each is an annulus fibrosus. Figure 9. Components of cardiac skeleton (blue) as viewed from above with atria removed. Figure 13.4 in Histology: A Text and Atlas (Ross & th Pawlina, 6 ed., 2011). b. The core of the valve cusps (leaflets) arise from this connective tissue as well. c. Histologically an annulus fibrosus just appears as dense irregular connective tissue (Figure 10, “fibrous skeleton”). Figure 10. Atrial and ventricular walls showing 3 layers of the heart wall on the left side of the heart and a section through 2. Trigona fibrosi (right an annulus fibrosus. Figure 13.8a from Histology: A Text th and Atlas (Ross & Pawlina, 6 ed., 2011). and left fibrous trigones): Triangular islands of connective tissue that serve to strengthen the annuli fibrosi. 3. Septum membranaceum (membranous part of the interventricular septum): An extension of the cardiac skeleton into the interventricular septum (Figure 8, label a). Microanatomy of the Heart Rod D. Braun Page 11 of 25 C. FUNCTIONS OF CARDIAC SKELETON 1. Separates atrial musculature from ventricular musculature. 2. Functions as sites of origin (points of insertion) of cardiac muscle. 3. Localizes and stabilizes valves. 4. Limits the diameter of valves. 5. Prevents spread of electrical impulses except via the conducting system. III. HEART WALL The wall of atria and ventricles is composed of three layers: A) epicardium, B) myocardium, and C) endocardium (Figures 3 and 10). A. EPICARDIUM: The external layer of the heart wall (Figures 10 and 11). 1. The epicardium is also known as Figure 11. Epicardium (bracketed) and myocardium (bottom). From Michigan Medical Histology the visceral reflection (layer) of (MacCallum, 2000). the serous pericardium (Figure 3). 2. It is analogous to the tunica adventitia of blood vessel walls. 3. The epicardium consists of: a. A layer of simple squamous epithelium Figure 12. Epicardium. Note: top of image is pericardial cavity. Fig 8.3a from Wheater’s Functional called mesothelium (M, Histology (Young & Heath, 4th ed., 2000). Figure 12) with its associated basal lamina. Microanatomy of the Heart Rod D. Braun Page 12 of 25 b. Epicardial connective tissue i. Contains fat (A), collagen fibers, elastic fibers (F), arteries, veins, and nerves (Figure 12). ii. The portion of this tissue connecting to the myocardium is often referred to as subepicardium. 4. The coronary arteries, cardiac veins, and nerves that supply the heart are located in the connective tissue, and are typically surrounded by adipose tissue (Figures 11 and 12). 5. Epicardium is the region where fat is stored in the heart. B. MYOCARDIUM: The middle layer of the heart wall containing the cardiac muscle cells. 1. It is analogous to the tunica media of blood vessel walls. 2. Cardiac muscle is composed of cardiac muscle cells (cardiomyocytes) (Figure 13). Remember: a. Cardiac muscle cells contain one or two nuclei, are packed with myofibrils and large Figure 13. Cardiac muscle in myocardium. Striations are mitochondria, and visible within the cells. Arrowheads identify intercalated discs between neighboring cardiac muscle cells. From connect to each other via Michigan Medical Histology (MacCallum, 2000). extensive intercalated discs (Figure 13, arrowheads). Microanatomy of the Heart Rod D. Braun Page 13 of 25 b. Intercalated discs (Figure 14) consist of: i. Fascia adherens (FA): connect two cardiac muscle cells via a junction binding to actin thin filaments in Figure 14. TEM of intercalated disc in myocardial cells. Fig 8.3a from Wheater’s Functional Histology (Young & Heath, th 4 ed., 2000). each cell. ii. Desmosomes (D): connect the two cells via desmin and vimentin intermediate filaments. iii. Gap junctions (N): provide for ionic communication and coupling between the cardiac muscle cells. 3. Differences in myocardial thickness (Figure 15): a. The atrial myocardium is thinner than ventricular myocardium. b. The myocardium of the left ventricle is three times thicker than the myocardium of the right ventricle. Microanatomy of the Heart Rod D. Braun Page 14 of 25 Figure 15. Schematic of the human heart demonstrating the relative thicknesses of the heart wall in the different chambers. Plate 228 (Chapter 4) from Atlas of Human Anatomy (Netter, F.H., th 7 ed., 2019). 4. Atrial myocardial cells are smaller (about 10 μm vs. 15-20 μm diameter; Figure 16), have a less elaborate t- tubule system, and have more gap junctions. Figure 16. SEM images of atrial (left) and ventricular (right) cardiac muscle cells at same magnification. Modified from Figure 3 in Miyamoto et al., Heart Vessels 16:232-240 (2002). Microanatomy of the Heart Rod D. Braun Page 15 of 25 5. Atrial and ventricular cardiac muscle cells both release a hormone. a. Atrial cardiac muscle cells produce, store, and secrete a polypeptide called atrial natriuretic factor (ANF, atrial natriuretic polypeptide, ANP). i. ANF is stored in electron dense Figure 17. TEM of atrial cardiac muscle cell. Arrows: ANF granules. Fig 12-3 in Histology and st Cell Biology (Kierszenbaum, 1 ed., 2002). granules (Figure 17). ii. Released into surrounding capillaries when atrial wall is stretched. b. Ventricular cardiac muscle cells store and release brain natriuretic peptide (BNP). i. Called BNP because it was first discovered in the brain. ii. Stored in granules and released into surrounding capillaries when ventricular wall is stretched. c. Physiological effects of ANF (ANP) and BNP i. The receptors for these molecules are found in cells in the adrenal cortex, kidney, and vascular smooth muscle. ii. ANF and BNP stimulate the kidney to excrete sodium and water in the urine and function in maintaining blood volume. Microanatomy of the Heart Rod D. Braun Page 16 of 25 iii. These effects will be covered in more detail in a subsequent Physiology lecture. C. ENDOCARDIUM: The internal layer of the heart wall. 1. Endocardium lines cardiac valves and papillary muscles, as well as the inner walls of the atria and ventricles. 2. The endocardium is analogous to the tunica intima of blood vessels. 3. The endocardium consists of: a. Endothelium (simple squamous epithelium) with associated basal lamina (Figure 18). Figure 18. Endocardium of atrial wall. Top: lumen of atrium, Bottom: myocardium. Note endothelial cells lining b. Endocardial atrial lumen. connective tissue i. Contains fibroblasts, collagen fibers, elastic fibers, and some smooth muscle cells. ii. The deeper layer of this connective tissue, where it connects to the myocardium, is often called the subendocardial layer. IV. IMPULSE CONDUCTION SYSTEM A. CHARACTERISTICS 1. The impulse conduction system consists of specialized cardiac muscle fibers that initiate and conduct electrochemical impulses resulting in the coordinated contraction and relaxation of the heart. Microanatomy of the Heart Rod D. Braun Page 17 of 25 2. Control of contractions a. Cardiac muscle is capable of contracting without any stimulus from the nervous system, although the autonomic nervous system modulates heart rate. b. Stimulation of sympathetic nerves accelerates heart rate, while stimulation of parasympathetic nerves slows heart rate. 3. Components of the conduction system (Figure 19 and 20): a. Impulse is initiated in the sinoatrial node (SA node). b. Impulse travels through the atrial muscle, resulting in Figure 19. Impulse conduction system of heart. Figure atrial contraction. 13.5 in Histology: A Text and Atlas (Ross & Pawlina, 7th ed., 2016). c. Impulse is also conducted to the atrioventricular node (AV node) via specialized internodal fibers. At AV node, the signal is delayed Figure 20. Impulse conduction system of heart, showing conduction speeds of each component. (Figure 20). Microanatomy of the Heart Rod D. Braun Page 18 of 25 d. From the AV node, the impulse passes to the Bundle of His and the left and right bundle branches, which rapidly transmit the impulse through the interventricular septum (Figure 19). e. The impulse is then conducted to the Purkinje fibers, which pass the impulse along at 4 m/sec (Figure 20). f. The Purkinje fibers deliver the impulse to a subset of ventricular cardiac muscle cells. g. The stimulated ventricular cardiac muscle cells conduct the impulse to other ventricular cardiac muscle cells via gap junctions in intercalated discs, resulting in ventricular contraction. 4. Electrocardiogram (ECG, EKG) a. The conduction of electrical contraction impulses through the heart is responsible for the voltage trace recorded as the ECG (Figure 21). b. Details on the ECG will be provided by Dr. Figure 21. Impulse conduction system of heart. Relationship of path of impulse to EKG. Lasley in a series of Physiology lectures. Microanatomy of the Heart Rod D. Braun Page 19 of 25 B. SINOATRIAL (SA) NODE 1. Location a. SA node lies in the wall of the right atrium close to the orifice of the superior vena cava Figure 22. SA node surrounding branch of coronary (Figure 19). artery (trichrome stain). Smaller nodal cells are interspersed in connective tissue outside the arterial tunica adventitia. Larger atrial myocardial cells at top left. From University of Kansas Medical Center b. SA node often surrounds a branch of the coronary artery (Figure 22). 2. SA nodal cells a. Modified cardiac muscle cells that are spindle shaped and smaller than normal cardiac muscle cells (5-7 μm diameter). (Figures 22 and 23) b. Myofibrils are fewer in number and less organized Figure 23. SEM of SA nodal cells. Note spindle shape and small size (compare to Figure 16). than normal cardiac muscle Modified from Fig 4 in Miyamoto et al., Heart Vessels 16:232-240 (2002). cells. Therefore, SA nodal cells typically exhibit a paler staining appearance in H&E or trichrome (Figure 22). c. SA nodal cells are joined by intercalated discs that are less well developed than in normal cardiac muscle cells. 3. Since contraction of the heart (about 70 beats/minute) is initiated at the SA node, it is referred to as the pacemaker. Microanatomy of the Heart Rod D. Braun Page 20 of 25 4. The SA node initiates an impulse that spreads through atrial cardiac muscle cells, causing contraction, and along tracts of modified cardiac muscle fibers (internodal fibers) to the atrioventricular node (AV node). C. ATRIOVENTRICULAR (AV) NODE 1. Location: Lies in the floor of the right atrium just above the tricuspid valve (Figure 19). 2. AV nodal cells Figure 24. Top: LM of AV nodal cells (fibers). Bottom: LM a. AV nodal cells appear of AV nodal cells connecting with fibers from Bundle of His. as a mass of small, pale-staining cells isolated by connective tissue (Figure 24). b. They are similar to SA nodal cells in appearance. c. Cells are roughly spindle shaped and in some areas form a Figure 25. SEM of AV nodal cells. Note size and formation of meshwork. Modified from reticular meshwork (Figure 25). Fig 4 in Miyamoto et al., Heart Vessels 16:232-240 (2002). d. Intercalated discs connect the cells, but they are poorly developed. 3. The impulse is delayed in the AV node to allow filling of the ventricles. Then the impulse passes into the Bundle of His (Figures 19, 20, and 24). Microanatomy of the Heart Rod D. Braun Page 21 of 25 D. BUNDLE OF HIS (AV BUNDLE) AND LEFT AND RIGHT BUNDLE BRANCHES 1. Course of bundle of His a. Runs from the AV node in the right atrium into the interventricular septum by traversing the right fibrous trigone of the cardiac skeleton (Figure 9 and Figure 19). b. Then it runs along the margin of the septum membranaceum (Figure 26). 2. The Bundle of His divides Figure 26. Bundle of His (bracketed) in septum into left and right bundle membranaceum. Trichrome stain. From Michigan Medical Histology. D.K. MacCallum (2000). branches in the interventricular septum (Figure 19). 3. Cells in the bundles are larger than the nodal cells, but still have fewer myofibrils than typical cardiac muscle cells. 4. The branches terminate in the connective tissue between the endocardium and myocardium (subendocardium) of the right and left ventricles, where they connect to Purkinje fibers. Figure 27. Purkinje fibers (P) in subendocardium. E: endocardium, M: myocardium. Figure 8.4a in E. PURKINJE FIBERS th Wheater’s Functional Histology (Young & Heath, 4 ed., 2000). 1. Located in the subendocardial connective tissue of ventricular endocardium (Figure 27). Microanatomy of the Heart Rod D. Braun Page 22 of 25 2. These fibers transmit impulses to a subset of ventricular cardiac muscle cells at the endocardium/myocardium interface. Note: In some larger animals, e.g., cows, Purkinje fibers extend deep into the myocardium as intramural Purkinje fibers, but there is no evidence that this occurs in humans. In humans the Purkinje fibers are restricted to the subendocardial tissue and the inner myocardium. 3. Characteristics of Purkinje fibers: a. Larger than normal cardiac muscle cells (Figure 26). b. The large amount of glycogen in these cells makes them look pale-staining and vacuolated (Figure 26). c. Cells and nuclei are more rounded in appearance than normal cardiac muscle cells. d. Contain few myofibrils and lack a T tubule system (Figure 28). e. Connected by intercalated discs, but the connections are less well developed than those found in Figure 28. Isolated cardiac cells stained with a fluorescent normal cardiac muscle membrane marker. A: Purkinje fiber, B: ventricular cardiac muscle cell. Note lack of T-tubules in Purkinje fiber (A). (Cordeiro et al., J. Physiol., 531: 301-314, 2001). cells. Microanatomy of the Heart Rod D. Braun Page 23 of 25 V. VALVES OF THE HEART Cardiac valves control the direction of blood flow through the heart (Figure 6, reproduced at the right). A. FOUR VALVES (Figures 6 and 7) 1. Left atrioventricular (mitral or bicuspid) valve: 2 cusps 2. Right atrioventricular (tricuspid) valve: 3 cusps 3. Pulmonary semilunar valve: 3 cusps Figure 6. Chambers of the heart and path of blood flow. Figure 13-4 in Textbook of Medical Physiology th 4. Aortic semilunar valve: 3 cusps (Guyton, 6 ed., 1980). B. STRUCTURE OF VALVES (Figure 29) 1. Cardiac valves extend from the annuli fibrosi of the cardiac skeleton (FS in Figure 29). 2. The valves consist of a core of fibrous dense irregular Figure 29. Heart valve. S = fibroelastic supporting layer, M connective tissue, the = myocardium, E = endocardium, F = fibrosa, FS = fibrous skeleton (fibrous ring or annulus fibrosi). Modified from Fig fibrosa (F), continuous with 8.5 from Wheater’s Functional Histology (Young & Heath, 4th ed., 2000). annuli fibrosi (FS). 3. Valves are covered on the free atrial and ventricular surfaces by endocardium (E). Microanatomy of the Heart Rod D. Braun Page 24 of 25 C. CHORDAE TENDINEAE 1. The atrioventricular valves are attached to the heart wall by fibrous cords of dense regular connective tissue that extend from the free edges of the valves to papillary muscles (fingerlike muscular Figure 30. Sagittal section of posterior wall of left ventricle and projections extending posterior cusp of mitral valve. Modified from Figure 13.9a in th Histology: A Text and Atlas (Ross & Pawlina, 7 ed., 2016). from the ventricular walls, Figures 7, 15, and 30). 2. These fibrous cords are called chordae tendineae (Figures 30 and 31). 3. Under the control of the papillary muscles, they function to prevent eversion of Figure 31. Chordae tendineae linking papillary muscle to heart atrioventricular valve valve. Trichrome stain. From Michigan Medical Histology. D.K. MacCallum (2000). leaflets. Microanatomy of the Heart Rod D. Braun Page 25 of 25 References: Gartner, L.P. and Hiatt, J.L., Color Atlas of Histology, 3rd ed., Lippincott Williams & Wilkins: Philadelphia, 2000, Ch. 8. Kierszenbaum, A.L., Histology and Cell Biology: An Introduction to Pathology, 1st ed., Mosby: St. Louis, 2002, Ch. 12. MacCallum, D.K., Michigan Medical Histology, University of Michigan, Ann Arbor, 2000. Ross, M.H. and Pawlina, W., Histology: A Text and Atlas, 6h ed., Lippincott Williams & Wilkins: Philadelphia, 2011, Ch. 13. Ross, M.H. and Pawlina, W., Histology: A Text and Atlas, 7th ed., Lippincott, Williams, & Wilkins, WoltersKluwer Health: Philadelphia, 2016, Ch. 13. (major source) Young, B. and Heath, J.W., Wheater’s Functional Histology: A Text and Colour Atlas, 4th ed., Churchill Livingstone: Edinburgh, 2000, Ch. 8. RDB: 09/15/2022