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Epithelial Tissue Elena Stark, MD, PhD Stephen Schettler, PhD Department of Pathology & Laboratory Medicine David Geffen School of Medicine at UCLA Contributor: Paul Frank DGSOM Class of 2014 THIS FILE HAS COPYRIGHTED MATERIAL. IT IS INTENDED FOR YOUR USE ONLY. DO NOT DISTRIBUTE OR SHARE IT. Nongraphical content and organization Copyright 2012 M.E. Stark, MD, PhD. 1 3 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 26 27 28 30 32 33 36 37 38 39 41 1. Epithelial Tissue – Introduction 2. Epithelia – Types 2.1 Epithelia – Types – Simple Squamous 2.1/2.2 Epithelia – Types – Simple Squamous/Simple Cuboidal – Visualization 2.2 Epithelia – Types – Simple Cuboidal 2.3 Epithelia – Types – Simple Columnar 2.4 Epithelia – Types – Stratified Squamous 2.5 Epithelia – Types – Pseudostratified 2.6 Epithelia – Types – Transitional 2.7 Epithelia – Types – Recap; Next Topics 3. Epithelia – Cell Surfaces 3.1 Epithelia – Cell Surfaces – Lateral Surface 3.1.1 Epithelia – Cell Surfaces – Lateral Surface – Zonulae Adherentes 3.1.2 Epithelia – Cell Surfaces – Lateral Surface – Desmosomes 3.1.3 Epithelia – Cell Surfaces – Lateral Surface – Tight Junctions 3.1.4 Epithelia – Cell Surfaces – Lateral Surface – Gap Junctions 3.2 Epithelia – Cell Surfaces – Cell Junctions, Image 3.3 Epithelia – Cell Surfaces – Recap; Next Topics 4. Epithelia – Basement Membrane 4.1 Epithelia – Basement Membrane – Hemidesmosomes 4.2 Epithelia – Basement Membrane – Recap; Next Topics 5. Epithelia – Exocrine Glands 5.1 Epithelia – Exocrine Glands – Shape of Duct 5.2 Epithelia – Exocrine Glands – Shape of Secretory Portion 5.3 Epithelia – Exocrine Glands – Mode of Secretion 5.4 Epithelia – Exocrine Glands – Type of Secretion 5.5 Epithelia – Exocrine Glands – Adenocarcinoma 5.6 Epithelia – Exocrine Glands – Recap; Next Topics 6. Epithelia – Endothelium and Mesothelium 7. Epithelial Tissue – Image Sources The “Back to Main Menu” button has been disabled on pages 43 to 92 (these are the hyperlink/highlight pages). To return to the Main Menu: first, go back to the original page by clicking BACK or ; Then click the “Back to Main Menu” button, as it is functional on pages 3 to 42. 2 1. Epithelial Tissue – Introduction Epithelia are present in all organs of the body, in conjunction with the other 3 types of tissue. Epithelia usually sit on a layer of connective tissue (which usually sits on muscle tissue) with nerves interspersed throughout. The term epithelia (singular: epithelium) refers to specialized cells that: a. Cover all the surfaces of the body (ie, skin, gums) b. Line the lumen, or internal cavity, of hollow organs (ie, lining of blood vessels, lining of the digestive tract). As you will see throughout your medical school career, all organs of the body are compartmentalized and lined by something. In almost every case, the something is a layer of epithelial cells. As an example, the image at right shows a cross-section of the wall of the heart, which is formed by the endocardium, myocardium, and the epicardium. The external surface of the heart (the surface exposed to the chest cavity) is covered by a layer of cells (epithelium) that covers and constitutes part of the epicardium . Meanwhile, the internal cavity of the heart – called the lumen – is exposed to the blood being pumped through the heart. The lumen is lined by a layer of cells (epithelium) that covers and constitutes part of the endocardium , this particular epithelium has a special name: endothelium (more on this later). 3 1. Epithelial Tissue – Introduction To illustrate the general concept, here is another example of how epithelia line and cover organs. Also note other tissues in between layers of epithelia, such as connective tissue layers, muscle layers, and nerves interspersed throughout. Don’t worry about knowing which is which at this point. The figure illustrates the concept of epithelia lining and covering organs. (We do NOT expect you to know which layer is which now, we will study all those layers and structures in detail in Block 3.) The point here is to show you that the digestive tract is lined by an epithelium and covered by another epithelium . Between these epithelia we observe connective tissue; and sandwiched in between are layers of muscle (depicted as the darker red layers); with nerves (depicted as yellow lines or meshes) interspersed. The figure is a portion of the small intestine. 4 1. Epithelial Tissue – Introduction Remembering from the module “Introduction to Histological Tissues,” epithelia have abundant cells and a very small amount of extracellular material (ECM) . This is a high magnification (about x600) of the epithelium in the respiratory tract. (Ignore the i.ds in the image.) 5 2. Epithelia – Types There are different types of epithelia. Try to think of how the structure of each type of epithelium may relate to its function. Epithelia are typically classified by the following criteria: – Number of layers of cells – Shape of the cells If there is only 1 layer of cells, the epithelium is called simple. If there are more, the epithelium is called stratified. Stratified epithelia are named for the shape of the cells on the top layer. There are 3 possible shapes of epithelial cells: – Squamous (flat-shaped) – Cuboidal (square-cube-shaped) – Columnar (column-shaped) Notice that all 3 of these illustrations (to the right) are of simple epithelia (ie, only 1 layer of cells). Under the cell layer, there are other layers (here in dark orange and pink) – most likely of connective tissue. 6 2. Epithelia – Types Simple or stratified is combined with the cell shape to name the different epithelia. Thus we have: • Simple squamous: 1 layer of flat cells • Simple cuboidal: 1 layer of square-cube-shaped cells • Simple columnar: 1 layer of column-shaped cells • Stratified squamous: 2 or more layers of cells where the top layer has flat cells Stratified cuboidal and stratified columnar epithelia do exist, but are rare (they will be presented in context, as they arise in later blocks). Note: there are 2 other types of epithelia: transitional and pseudostratified. These epithelia are NOT described as simple or stratified. (We will talk about them later in this module.) Simple squamous Simple cuboidal Simple columnar Stratified squamous 7 2.1 Epithelia – Types – Simple Squamous Now that we have the basic concept of the different types of epithelia, let’s look at them in histological slides. We will take these tissues 1 at a time. This is very important. Start training your eye to real histological images, understanding what you are observing. Simple squamous: 1 layer of flat cells Examples of locations: • Lining of blood and lymph vessels, and heart • Air sacs of lungs FORM FITS FUNCTION: The relatively thinness of this epithelium allows oxygen to diffuse through and into the underlying tissue; nutrients can be rapidly transported across, as well. In addition, it is possible for some types of cells to “crawl” between the spaces that exist between the cells of a simple squamous epithelium. ORIENT YOURSELF: To visualize the relationship between the figure and the image, take the flat sheet of cells (the figure at the top), mentally roll it into a cylinder, and look through the cylinder – like a telescope. The bottom image shows a cross-section of a capillary, which is always lined with a simple squamous epithelium, called endothelium. (More on endothelium in later slides.) A cell Image: cross-section of a capillary. 8 2.1/2.2 Epithelia – Types – Simple Squamous/Simple Cuboidal – Visualization How to visualize the relationship between a flat sheet of cells and a cross-section. 9 2.2 Epithelia – Types – Simple Cuboidal Simple cuboidal epithelium is very similar to simple squamous, the only difference being that the cells form a barrier that is a bit thicker. Simple cuboidal: 1 layer of square-cube-shaped cells Examples of locations: • Nephrons (tubules forming the internal architecture of kidneys) • Some glands and their ducts These epithelia line structures where secretion and/or absorption take place. FORM FITS FUNCTION: Cuboidal cells are actively involved in transporting substances into or out of a lumen, or into or out of the extracellular environment. As such, their cuboidal shape is a function of the additional cellular machinery required to carry out their role. ORIENT YOURSELF: To visualize the relationship between the figure and the image, take the flat sheet of cells (the figure at the top), mentally roll it into a cylinder, and look through the cylinder – like a telescope. The bottom image shows a cross-section of a portion of a nephron, which is the functional unit of the kidneys (to be covered in Block 2). A cell Image: cross-section of a portion of a nephron. 10 2.3 Epithelia – Types – Simple Columnar Simple columnar epithelium is very similar to simple cuboidal, the only difference being that the cells form a barrier that is even thicker. Simple columnar: 1 layer of column-shaped cells Examples of locations: • Lining of most of the digestive tract • Lining of the gallbladder • Some glands • Lining of small bronchi • Lining of the uterine tubes • Lining of portions of the uterus FORM FITS FUNCTION: These epithelia are lining structures where absorption and/or secretion of substances take place. ORIENT YOURSELF: The bottom image shows a portion of the wall of a villus, which is a finger-like projection found in the wall of the small intestine. A cell Longitudinal section. Make note of the plane in the illustration (above). 11 2.4 Epithelia – Types – Stratified Squamous Stratified squamous epithelium usually contains many cell layers. The theme with stratified epithelia in general is that they protect the underlying tissue. Stratified squamous: 2 or more layers of cells where the top layer is formed by flat cells Examples of locations: • Skin (shown in the image) • Lining of the oral cavity and esophagus • Lining of the vagina Basal layer : the deepest layer of cells in the epithelium. These cuboidal-appearing cells are the stem cell layer for this tissue. They constantly divide to replenish the lost or damaged layers above them. FORM FITS FUNCTION: This type of epithelium serves as a barrier for points of contact between the outside world and the body, where physical forces or exposure (to toxic chemicals, radiant energy, or infectious agents) takes place. These cells are replaced rapidly in order to maintain an intact barrier with the outside world. ORIENT YOURSELF: The bottom image shows skin cells. (This will be covered in lab, later in Block 1.) 12 2.5 Epithelia – Types – Pseudostratified A We mentioned earlier that there are 2 other types of epithelia that are NOT described as simple or stratified. The first type is pseudostratified epithelium. A B Pseudostratified epithelia are comprised of a single layer of cells attached to the same basement membrane**. The appearance is stratified because this epithelium is made up of several different types of cells of varying heights that become superimposed over each other. B Examples of location: • Upper respiratory tract (most commonly) (This will be covered in detail in Block 2.) ORIENT YOURSELF: The image at right shows an example of pseudostratified epithelium of the trachea. **All epithelia rest on a layer of tissue called basement membrane (details later). For now, know that the layer of cells in every simple epithelium and the deepest layer of a stratified epithelium attach to a basement membrane. A cell 13 2.6 Epithelia – Types – Transitional The second type of epithelium that is NOT simple or stratified is transitional epithelium. It changes appearance based on distension of the lumen of the organ it lines. It is a specialized stratified epithelium. Location: • Unique to the urinary system (bladder, ureter, urethra, etc) and appears different depending on whether the organ it lines is full or empty. When the organ is distended (full), the epithelium resembles a simple squamous epithelium. When the organ is empty or relaxed, the epithelium will appear stratified and cuboidal. One key feature of a transitional epithelium in a relaxed state is a “scalloped” appearance of the lumenal layer of cells. (We will go into more detail in Blocks 2 and 3.) ORIENT YOURSELF: The top image shows the entire wall of a full urinary bladder including its transitional epithelium , which appears very flat because it is distended (full). The arrow is on the lumen (space within the bladder). The bottom image shows a portion of the wall of an empty urinary bladder. Notice the appearance of the epithelium, it looks stratified cuboidal. 14 2.7 Epithelia – Types – Recap; Next Topics Topics covered so far: • The 6 most common types of epithelia and their very general locations and functions. • All epithelia have an abundance of cells and very little ECM. The cells are very close to one another. In epithelia it is very important that the cells remain very close to one another because of the tissue functions. Topics to be covered next: - Junctions – the structures that attach the cells to each other. There are different types of junctions between epithelial cells. - The basement membrane – a layer of connective tissue that epithelia rest on. (This is a very important structure.) - Exocrine glands – structures that secrete something to the exterior. Sometimes epithelia fold to form glands. Glands in the human body are structures that secrete something either to the exterior or into the bloodstream. - Two specialized types of simple squamous epithelia – endothelium (plural: endothelia) and mesothelium (plural: mesothelia). (We will introduce these in this module, and encounter them again in future blocks.) 15 3. Epithelia – Cell Surfaces Epithelial cells are very close to one another and must remain in tight proximity. Thus, there are structures between the cells that keep them “attached.” The figure represents 2 epithelial cells. Here we can see a simple cuboidal epithelium, but these concepts apply to all epithelia. ORIENT YOURSELF: • Notice that the epithelial cells are “on top” of another tissue, this is connective tissue – we call it the basement membrane. (More on this later.) • The space at the top of the figure would be an opening or space, called the cavity. It is lined by epithelial cells. If these cells were in the GI tract, the space would be the lumen of the GI tract. The epithelial cells have 3 sides: 1. Apical or lumenal surface (this particular figure shows finger-like projections, called cilia or microvilli – depending on their size – but NOT all epithelial cells have these) 2. Lateral surface 3. Basal surface Underlying connective tissue. 16 3.1 Epithelia – Cell Surfaces – Lateral Surface Epithelial cells have 3 surfaces. The apical or lumenal surface is closest to the lumen. The basal surface is closest to the connective tissue underlying the epithelium. The lateral surface is where the cell junctions are located. The lateral surface of epithelial cells contains cell junctions that attach contiguous epithelial cells to one another. In histology these junctions are classified as “stronger” and “weaker”: 1. Stronger junctions hold cells tightly together; they are called anchoring junctions. There are 2 types of these: - Zonulae adherentes - Desmosomes 2. Weaker junctions assist in holding cells together. There are 2 types of these: - Tight junctions (the choice of words is confusing… but that is what they are called…) - Gap junctions Underlying connective tissue. The following slides elaborate on both strong and weak junctions. 17 3.1.1 Epithelia – Cell Surfaces – Lateral Surface – Zonulae Adherentes Zonulae adherentes (singular: zonula adherens) are a type of “strong” or anchoring cell junctions. Zonula Adherens EPITHELIAL CELL Actin filaments Anchor proteins Cadherins (Ca2+ dependent) EPITHELIAL CELL Anchor proteins Actin filaments Zonulae adherentes have the structure represented above and at right: – Notice the green lines in the figure above, they represent transmembrane proteins. They go through the membrane of each epithelial cell, linking the contiguous epithelial cells. These proteins are cadherins. They are attached to each cell and link to each other (cadherin to cadherin) in the intercellular space. – Cadherins of each epithelial cell also link to anchor proteins in the cytoplasm, which in turn link to actin filaments of the cytoskeleton of the cell. Thus a zonula adherens has the following 3 components: – Cadherins (transmembrane proteins) – Anchor proteins – Actin filaments (these are really part of the cytoskeleton of the cell, but they contribute to the zonula adherens) Underlying connective tissue. Zonulae adherentes tend to be close to the apical surface, but are still on the lateral surface. 18 3.1.2 Epithelia – Cell Surfaces – Lateral Surface – Desmosomes Desmosomes are the other type of “strong” or anchoring cell junctions. Desmosome EPITHELIAL CELL Keratin filaments Anchor proteins Cadherins (Ca2+ dependent) EPITHELIAL CELL Anchor proteins Keratin filaments Desmosomes have very similar structure to the zonulae adherentes: – Cadherins (transmembrane proteins) – Anchor proteins BUT instead of actin filaments they have – Keratin filaments, also called intermediate filaments Keratin is much stronger than actin; thus, desmosomes are stronger than zonulae adherentes. Desmosomes are described as forming button-like junctions. They tend to be positioned near a zonula adherens, although towards the basal surface of the cell; but still on the lateral surface. Underlying connective tissue. CLICK HERE FOR A CLOSER VIEW OF A DESMOSOME. 19 3.1.3 Epithelia – Cell Surfaces – Lateral Surface – Tight Junctions Tight junctions are “weak” cell junctions. Tight Junction EPITHELIAL CELL EPITHELIAL CELL Transmembrane protein Transmembrane protein (Ca2+ dependent) Tight junctions Tight junctions are formed when the extracellular domains of transmembrane proteins (on the lateral surfaces of adjacent cells) interlock with the help of calcium. Some membrane structures (ie, ion channels) are found only on the apical surface or only on the basolateral surface. Tight junctions help keep these structures on the proper surface, thus maintaining the polarization of the cell. Tight junctions can block the passage of lumenal content between cells. Underlying connective tissue. The cytoskeleton of the cell does NOT contribute to tight junctions. 20 3.1.4 Epithelia – Cell Surfaces – Lateral Surface – Gap Junctions Gap junctions are the other type of “weak” cell junctions. Gap Junction EPITHELIAL CELL EPITHELIAL CELL Connexon Gap junctions Gap junctions are formed by transmembrane proteins, called connexins. Many connexin protein chains form a connexon. Gap junctions create a channel whereby cytoplasm and its water-soluble contents can flow between cells to couple the cells metabolically and electrically. The cytoskeleton of the cell does NOT contribute to the structure of gap junctions. Underlying connective tissue. 21 3.2 Epithelia – Cell Surfaces – Cell Junctions, Image So far we have used an illustration to show epithelial cell junctions, as these are NOT visible through the Light Microscope. Here we show a TEM image with several cell junctions. Legend TJ = tight junction (referred to by some authors as zonula occludens) ZA = zonula adherens D = desmosome TEM image of a portion of 2 epithelial cells. 22 3.3 Epithelia – Cell Surfaces – Recap; Next Topics Topics covered so far: • The 6 most common types of epithelia and their very general locations and functions. • The different types of junctions between epithelial cells. Topics to be covered next: - The basement membrane – a connective tissue layer underlying an epithelium. -Exocrine glands – formed by an epithelium that folds in on itself; the cells in that epithelium secrete something to the exterior of the body. - Two specialized types of epithelia – endothelium (plural: endothelia) and mesothelium (plural: mesothelia). (We will introduce these in this module, and encounter them again in future blocks.) 23 4. Epithelia – Basement Membrane All epithelia rest on a layer of connective tissue, called the basement membrane. The basement membrane (BM) is a thin fibrous connective tissue layer between the epithelium and the underlying supporting tissue . All epithelia are avascular (ie, they contain NO blood vessels). In order to receive nutrition from the blood, epithelia rest superficial to a layer of supporting tissue which contains blood vessels. The basement membrane is between the epithelium and the supporting connective tissue. Blood vessels do NOT penetrate the basement membrane; however, it allows transudate (fluid leaked out of the vasculature) to serve the cells of the overlying epithelium. The basement membrane controls permeability to and from the epithelium. Nerves course through underlying tissue and must penetrate the basement membrane in order to innervate the epithelium. Thus, nerves do penetrate the basement membrane. Another very important function of the basement membrane is that it controls epithelial growth, impeding the epithelium from growing “downward.” In malignant growth, the epithelium crosses over the basement membrane. 24 4. Epithelia – Basement Membrane The basement membrane is produced by both the epithelium and the underlying supporting tissue. The basement membrane is a non-cellular structure produced by 2 types of cells: • Epithelial cells that are supported by the basement membrane • Fibroblasts, which are cells of the underlying supporting tissue The primary components of the basement membrane are: • Type IV collagen (unlike other types, collagen type IV forms flat sheets, NOT cords) • Heparan sulphate, which is a glycosaminoglycan • Ground substance, which is a gel-like suspension of glycoproteins and proteoglycans that includes • Fibronectin • Laminin • Entactin Laminin is the most common glycoprotein in the basement membrane. It attaches to: 1- Other components of the basement membrane, 2- Transmembrane proteins in the epithelial cell, called integrins. Integrins transmit information about external stress to the nucleus of the epithelial cell. This is important when responding to and recovering from injury. BM A basement membrane (BM) supporting a pseudostratified epithelium (illustration and image). Ignore the other i.ds. 25 4.1 Epithelia – Basement Membrane – Hemidesmosomes Hemidesmosomes link epithelial cells to the basement membrane. Epithelia that experience high abrasive force are reinforced by junctions called hemidesmosomes, which are similar to desmosomes in the lateral surface of adjacent epithelial cells (as previously described). Refer to the previous slide, as we describe the main components of a hemidesmosome: 1- Laminin in the basement membrane 2- Anchor proteins 3- Integrin proteins in the epithelial cells that happen to be attached to keratin of the cytoskeleton of the epithelial cell. NOTE: With Light Microssopes basement membranes can be seen if they are thick or if they have been specifically stained. The basement membrane in this image is particularly thick. With EM, the 3 sublayers of a basement membrane can be seen. While the distinction of these constitutes too much detail for our purposes, know that these layers are called: • Lamina lucida • Lamina densa (or basal lamina**) • Lamina fibroreticularis **Some authors refer to the basement membrane as the basal lamina (1 of its 3 sublayers). However, this may lead to confusion, so we will refer to the basement membrane as the basement membrane. 26 4.2 Epithelia – Basement Membrane – Recap; Next Topics Topics covered so far: • The 6 most common types of epithelia and their very general locations and functions. • The different types of junctions that attach epithelial cells to each other. • The basement membrane, which is a connective tissue layer underlying an epithelium. Topics to be covered next: - Exocrine glands – formed by an epithelium that folds on itself; the cells in that epithelium secrete something to the exterior. -Two specialized types of epithelia – endothelium (plural: endothelia) and mesothelium (plural: mesothelia). (We will introduce these in this module, and encounter them again in future blocks.) 27 5. Epithelia – Exocrine Glands Glands in the human body are structures that secrete something either into the exterior (then called exocrine glands) or into the bloodstream (then called endocrine glands). Only exocrine glands are presented here (however, we will discuss endocrine glands in Block 3). Epithelia can invaginate, or fold inward, to form exocrine glands. For example, mammary glands, digestive glands, and sweat glands all arise from epithelial tissue. These glands secrete their products into ducts that ultimately lead to the exterior of the body (and NOT into the blood stream). Can you see a folded epithelium in the figure? 28 5. Epithelia – Exocrine Glands Exocrine glands are formed by epithelial cells that specialize in secreting some substance to the exterior. Exocrine glands are formed when the cells in an epithelium proliferate and invaginate. The gland has a space in the center called the lumen. The cells closest to the surface, in conjunction with the corresponding lumen, form the duct of the gland . The rest of the gland is the secretory portion . Observe the apical surface of the cells in the gland. Observe the lateral surface of the cells in the gland. Observe the basal surface of the cells in the gland. The gland is surrounded by blood capillaries . 29 5.1 Epithelia – Exocrine Glands – Shape of the Duct Exocrine glands are classified in a number of ways according to the: 1- Shape of the duct 2- Shape of the secretory portion 3- Mode of secretion 4- Type of secretion Exocrine glands are classified, as the following, according to the shape of their duct: •Short •Long and coiled (We will elaborate in lab.) Short duct Long coiled duct 30 5.1 Epithelia – Exocrine Glands – Shape of the Duct Notice how a cut through a coiled duct looks on a slide. Keep this in mind when looking at virtual slides in lab. The illustration does NOT match perfectly, as this is only to show the concept. 31 5.2 Epithelia – Exocrine Glands – Shape of the Secretory Portion Exocrine glands are classified in a number of ways according to the: 1- Shape of the duct 2- Shape of the secretory portion 3- Mode of secretion 4- Type of secretion Exocrine glands can be described, as the following, according to the anatomical arrangement of the gland cells – ie, the shape of the secretory portion: •Acinar or alveolar (glands of this type resemble bunches of grapes) •Tubular (glands of this type are simple tube-like, U-shaped portion) Acinar gland. Acinar gland cross-section. ; Tubular gland. In the images, note the difference between a cross-section and a longitudinal section. Tubular gland longitudinal or sagittal section. ; 32 5.3 Epithelia – Exocrine Glands – Mode of Secretion Exocrine glands are classified in a number of ways according to the: 1- Shape of the duct 2- Shape of the secretory portion 3- Mode of secretion 4- Type of secretion Exocrine glands can also be described according to the gland cells’ mode of secretion (there are 3 modes): 1- Merocrine – the secretory product is released from the cell via exocytosis Merocrine 33 5.3 Epithelia – Exocrine Glands – Mode of Secretion Exocrine glands are classified in a number of ways according to the: 1- Shape of the duct 2- Shape of the secretory portion 3- Mode of secretion 4- Type of secretion Exocrine glands can also be described according to the gland cells’ mode of secretion (there are 3 modes): 2- Apocrine – the apical portion of the cell, which contains the secretory product, breaks away from the rest of the cell Apocrine 34 5.3 Epithelia – Exocrine Glands – Mode of Secretion Exocrine glands are classified in a number of ways according to the: 1- Shape of the duct 2- Shape of the secretory portion 3- Mode of secretion 4- Type of secretion Exocrine glands can also be described according to the gland cells’ mode of secretion (there are 3 modes): 3- Holocrine – the entire cell breaks apart, beginning with the rupture of the plasma membrane; the secretory product is released into the duct (along with fragments of the dead cell) Holocrine 35 5.4 Epithelia – Exocrine Glands – Type of Secretion Exocrine glands are classified in a number of ways according to the: 1- Shape of the duct 2- Shape of the secretory portion 3- Mode of secretion 4- Type of secretion Finally, exocrine glands are classified, as the following, according to the type of secretion: •Mucous glands – secrete mucus, which is rich in mucigens (large glycosolated proteins that absorb water and, as a result, produce a thick gel-like material). •Serous glands – secrete a viscous fluid rich in proteins (that are often enzymes) not as thick as mucus. Other exocrine glands are specialized in secreting substances like sweat (sweat glands), sebum/oil (sebaceous glands), or milk (mammary glands). (We will cover these in more detail as we proceed through the different systems in Blocks 2 and 3.) In general with use of H&E, serous cells stain darker than mucous cells . The exact shade of color is dependent on the sample, as there can be variations – depending on the composition of the secretion, and on the degree in which the sample “takes the stain in.” In this course, we will give you examples that are clearly lighter (for mucous cells) and clearly darker (for serous cells). 36 5.5 Epithelia – Exocrine Glands – Adenocarcinoma Tumors developing from glandular epithelium are called adenocarcinomas. Because there are epithelial glands in many organs – such as the stomach, uterus, colon, pancreas, liver, prostate, breast, and thyroid – we refer to adenocarcinomas in these organs when the epithelial cells in their respective glands become neoplastic. In some adenocarcinomas, the epithelial cells have a fairly normal morphology; but they secrete abnormal amounts of mucus. In other adenocarcinomas, the epithelial cells form very atypical glands that have abnormal cell morphology. •Normal glandular epithelium in the endocervix •Adenocarcinoma (Observe the difference in the glandular epithelial cells; don’t worry about the details at this point, you’ll learn them next year, just focus on the concept for now). 37 5.6 Epithelia – Exocrine Glands – Recap; Next Topics Topics covered so far: • The 6 most common types of epithelia and their very general locations and functions. • The different types of junctions that attach epithelial cells to each other. • The basement membrane, which is a connective tissue layer underlying an epithelium. • Exocrine glands – mucous glands, serous glands; sweat glands, sebaceous glands, and mammary glands – are formed by an epithelium that folds on itself; the cells in that epithelium secrete something to the exterior. Topics to be covered next: - Two specialized types of epithelia – endothelium (plural: endothelia) and mesothelium (plural: mesothelia) – these are considered membranes. (We will give examples in Blocks 2 and 3; as here, only the concept is important.) 38 6. Epithelia – Endothelium and Mesothelium Endothelium (plural: endothelia) and mesothelium (plural: mesothelia) are simple squamous epithelia that are specialized. Remember: simple squamous epithelia are formed by 1 layer of flat cells; and line and cover organs. Endothelium is the simple squamous epithelium lining that is specific to: the walls of the heart, blood vessels (arteries, veins, and capillaries), and lymphatic vessels. Endothelium : Notice that in arteries, veins, and capillaries, the most internal layer (lining) is an endothelium. (Ignore the labels; just focus on the concept.) 39 6. Epithelia – Endothelium and Mesothelium Endothelium (plural: endothelia) and mesothelium (plural: mesothelia) are simple squamous epithelia that are specialized. Remember: simple squamous epithelia are formed by 1 layer of flat cells; and line and cover organs. Mesothelium is a simple squamous epithelium that covers certain organs in the body and lines internal body cavities (lines CAVITIES; NOT organs). Cells forming mesothelia often secrete a substance called serous (viscous) fluid; thus, mesothelia are also referred to as serous membranes. Visualize the thoracic cavity lined by a mesothelium. The thoracic wall is internally lined by this tissue, which goes on to cover the outer aspect of the organs in the thoracic cavity – much like a blanket draping over the organs. Thus, the internal thoracic wall, the lungs, and heart are all covered by this mesothelium. Similarly, organs in the abdomen and pelvis are covered by a mesothelium. (If this is not clear, ask in lab.) The image at top shows a portion of an ovary – the pink part is the organ, the whitish-blue portion on the right side of the image is the pelvic cavity. Notice that the outermost layer (covering) of the ovary is a mesothelium . The bottom figure illustrates the location of mesothelium lining the thoracic wall and covering the lungs (real images shown in lab). (Ignore the labels; just focus on the concept.) Image: www.faculty.une.edu 40 7. Epithelial Tissue – Image Sources 1. Mescher AL. Junqueira’s Basic Histology. 12th ed. McGraw-Hill Medical; August 28, 2009. 2. Young B, et al. Wheater’s Functional Histology. 5th ed. Churchill Livingstone, Elsevier Limited; March 14, 2006. 3. Young B, et al. Wheater’s Basic Pathology. 5th ed. Churchill Livingstone, Elsevier Limited; December 15, 2009, 2010. 4. Gartner LP, Hiatt JL. Color Textbook of Histology. 3rd ed. W.B. Saunders Company; November 17, 2006. 5. University of New England, Biddeford & Portland, Maine; Westbrook College of Health Professions. University of New England Web site. http://www.faculty.une.edu. 2011. 6. University of Connecticut Health Center; Radiology, Department of Diagnostic Imaging and Therapeutics. University of Connecticut Health Center Web site. http://www.radiology.uchc.edu. 2011. 41 42 BACK 1. Epithelial Tissue – Introduction Epithelia are present in all organs of the body, in conjunction with the other 3 types of tissue. Epithelia usually sit on a layer of connective tissue (which usually sits on muscle tissue) with nerves interspersed throughout. The term epithelia (singular: epithelium) refers to specialized cells that: a. Cover all the surfaces of the body (ie, skin, gums) b. Line the lumen, or internal cavity, of hollow organs (ie, lining of blood vessels, lining of the digestive tract) As you will see throughout your medical school career, all organs of the body are compartmentalized and lined by something. In almost every case, the something is a layer of epithelial cells. As an example, the image at right shows a cross-section of the wall of the heart, which is formed by the endocardium, myocardium, and the epicardium. The external surface of the heart (the surface exposed to the chest cavity) is covered by a layer of cells (epithelium) that covers and constitutes part of the epicardium . Meanwhile, the internal cavity of the heart – called the lumen – is exposed to the blood being pumped through the heart. The lumen is lined by a layer of cells (epithelium) that covers and constitutes part of the endocardium , this particular epithelium has a special name: endothelium (more on this later). 43 BACK 1. Epithelial Tissue – Introduction Epithelia are present in all organs of the body, in conjunction with the other 3 types of tissue. Epithelia usually sit on a layer of connective tissue (which usually sits on muscle tissue) with nerves interspersed throughout. The term epithelia (singular: epithelium) refers to specialized cells that: a. Cover all the surfaces of the body (ie, skin, gums) b. Line the lumen, or internal cavity, of hollow organs (ie, lining of blood vessels, lining of the digestive tract) As you will see throughout your medical school career, all organs of the body are compartmentalized and lined by something. In almost every case, the something is a layer of epithelial cells. As an example, the image at right shows a cross-section of the wall of the heart, which is formed by the endocardium, myocardium, and the epicardium. The external surface of the heart (the surface exposed to the chest cavity) is covered by a layer of cells (epithelium) that covers and constitutes part of the epicardium . Meanwhile, the internal cavity of the heart – called the lumen – is exposed to the blood being pumped through the heart. The lumen is lined by a layer of cells (epithelium) that covers and constitutes part of the endocardium , this particular epithelium has a special name: endothelium (more on this later). 44 BACK 1. Epithelial Tissue – Introduction To illustrate the general concept, here is another example of how epithelia line and cover organs. Also note other tissues in between layers of epithelia, such as connective tissue layers, muscle layers, and nerves interspersed throughout. Don’t worry about knowing which is which at this point. The figure illustrates the concept of epithelia lining and covering organs. (We do NOT expect you to know which layer is which now, we will study all those layers and structures in detail in Block 3.) The point here is to show you that the digestive tract is lined by an epithelium and covered by another epithelium . Between these epithelia we observe connective tissue; and sandwiched in between are layers of muscle (depicted as the darker red layers); with nerves (depicted as yellow lines or meshes) interspersed. The figure is a portion of the small intestine. 45 BACK 1. Epithelial Tissue – Introduction To illustrate the general concept, here is another example of how epithelia line and cover organs. Also note other tissues in between layers of epithelia, such as connective tissue layers, muscle layers, and nerves interspersed throughout. Don’t worry about knowing which is which at this point. The figure illustrates the concept of epithelia lining and covering organs. (We do NOT expect you to know which layer is which now, we will study all those layers and structures in detail in Block 3.) The point here is to show you that the digestive tract is lined by an epithelium and covered by another epithelium . Between these epithelia we observe connective tissue; and sandwiched in between are layers of muscle (depicted as the darker red layers); with nerves (depicted as yellow lines or meshes) interspersed. The figure is a portion of the small intestine. 46 BACK 2. Epithelia – Types There are different types of epithelia. Try to think of how the structure of each type of epithelium may relate to its function. Epithelia are typically classified by the following criteria: – Number of layers of cells – Shape of the cells If there is only 1 layer of cells, the epithelium is called simple. If there are more, the epithelium is called stratified. Stratified epithelia are named for the shape of the cells on the top layer. There are 3 possible shapes of epithelial cells: – Squamous (flat-shaped) – Cuboidal (square-cube-shaped) – Columnar (column-shaped) Notice that all 3 of these illustrations (to the right) are of simple epithelia (ie, only 1 layer of cells). Under the cell layer, there are other layers (here in dark orange and pink) – most likely of connective tissue. 47 BACK 2. Epithelia – Types There are different types of epithelia. Try to think of how the structure of each type of epithelium may relate to its function. Epithelia are typically classified by the following criteria: – Number of layers of cells – Shape of the cells If there is only 1 layer of cells, the epithelium is called simple. If there are more, the epithelium is called stratified. Stratified epithelia are named for the shape of the cells on the top layer. There are 3 possible shapes of epithelial cells: – Squamous (flat-shaped) – Cuboidal (square-cube-shaped) – Columnar (column-shaped) Notice that all 3 of these illustrations (to the right) are of simple epithelia (ie, only 1 layer of cells). Under the cell layer, there are other layers (here in dark orange and pink) – most likely of connective tissue. 48 BACK 2. Epithelia – Types There are different types of epithelia. Try to think of how the structure of each type of epithelium may relate to its function. Epithelia are typically classified by the following criteria: – Number of layers of cells – Shape of the cells If there is only 1 layer of cells, the epithelium is called simple. If there are more, the epithelium is called stratified. Stratified epithelia are named for the shape of the cells on the top layer. There are 3 possible shapes of epithelial cells: – Squamous (flat-shaped) – Cuboidal (square-cube-shaped) – Columnar (column-shaped) Notice that all 3 of these illustrations (to the right) are of simple epithelia (ie, only 1 layer of cells). Under the cell layer, there are other layers (here in dark orange and pink) – most likely of connective tissue. 49 BACK 2.1 Epithelia – Types – Simple Squamous Now that we have the basic concept of the different types of epithelia, let’s look at them in histological slides. We will take these tissues 1 at a time. This is very important. Start training your eye to real histological images, understanding what you are observing. Simple squamous: 1 layer of flat cells Examples of locations: • Lining of blood and lymph vessels, and heart • Air sacs of lungs FORM FITS FUNCTION: The relatively thinness of this epithelium allows oxygen to diffuse through and into the underlying tissue; nutrients can be rapidly transported across, as well. In addition, it is possible for some types of cells to “crawl” between the spaces that exist between the cells of a simple squamous epithelium. ORIENT YOURSELF: To visualize the relationship between the figure and the image, take the flat sheet of cells (the figure at the top), mentally roll it into a cylinder, and look through the cylinder – like a telescope. The bottom image shows a cross-section of a capillary, which is always lined with a simple squamous epithelium, called endothelium. (More on endothelium in later slides.) A cell Image: cross-section of a capillary. 50 BACK 2.2 Epithelia – Types – Simple Cuboidal Simple cuboidal epithelium is very similar to simple squamous, the only difference being that the cells form a barrier that is a bit thicker. Simple cuboidal: 1 layer of square-cube-shaped cells Examples of locations: • Nephrons (tubules forming the internal architecture of kidneys) • Some glands and their ducts These epithelia line structures where secretion and/or absorption take place. FORM FITS FUNCTION: Cuboidal cells are actively involved in transporting substances into or out of a lumen, or into or out of the extracellular environment. As such, their cuboidal shape is a function of the additional cellular machinery required to carry out their role. ORIENT YOURSELF: To visualize the relationship between the figure and the image, take the flat sheet of cells (the figure at the top), mentally roll it into a cylinder, and look through the cylinder – like a telescope. The bottom image shows a cross-section of a portion of a nephron, which is the functional unit of the kidneys (to be covered in Block 2). A cell Image: cross-section of a portion of a nephron. 51 BACK 2.3 Epithelia – Types – Simple Columnar Simple columnar epithelium is very similar to simple cuboidal, the only difference being that the cells form a barrier that is even thicker. Simple columnar: 1 layer of column-shaped cells Examples of locations: • Lining of most of the digestive tract • Lining of the gallbladder • Some glands • Lining of small bronchi • Lining of the uterine tubes • Lining of portions of the uterus FORM FITS FUNCTION: These epithelia are lining structures where absorption and/or secretion of substances take place. ORIENT YOURSELF: The bottom image shows a portion of the wall of a villus, which is a finger-like projection found in the wall of the small intestine. A cell Longitudinal section. Make note of the plane in the illustration (above). 52 BACK 2.4 Epithelia – Types – Stratified Squamous Stratified squamous epithelium usually contains many cell layers. The theme with stratified epithelia in general is that they protect the underlying tissue. Stratified squamous: 2 or more layers of cells where the top layer is formed by flat cells Examples of locations: • Skin (shown in the image) • Lining of the oral cavity and esophagus • Lining of the vagina Basal layer : the deepest layer of cells in the epithelium. These cuboidal-appearing cells are the stem cell layer for this tissue. They constantly divide to replenish the lost or damaged layers above them. FORM FITS FUNCTION: This type of epithelium serves as a barrier for points of contact between the outside world and the body, where physical forces or exposure (to toxic chemicals, radiant energy, or infectious agents) takes place. These cells are replaced rapidly in order to maintain an intact barrier with the outside world. ORIENT YOURSELF: The bottom image shows skin cells. (This will be covered in lab, later in Block 1.) 53 BACK 2.4 Epithelia – Types – Stratified Squamous Stratified squamous epithelium usually contains many cell layers. The theme with stratified epithelia in general is that they protect the underlying tissue. Stratified squamous: 2 or more layers of cells where the top layer is formed by flat cells Examples of locations: • Skin (shown in the image) • Lining of the oral cavity and esophagus • Lining of the vagina Basal layer : the deepest layer of cells in the epithelium. These cuboidal-appearing cells are the stem cell layer for this tissue. They constantly divide to replenish the lost or damaged layers above them. FORM FITS FUNCTION: This type of epithelium serves as a barrier for points of contact between the outside world and the body, where physical forces or exposure (to toxic chemicals, radiant energy, or infectious agents) takes place. These cells are replaced rapidly in order to maintain an intact barrier with the outside world. ORIENT YOURSELF: The bottom image shows skin cells. (This will be covered in lab, later in Block 1.) 54 BACK 2.5 Epithelia – Types – Pseudostratified A We mentioned earlier that there are 2 other types of epithelia that are NOT described as simple or stratified. The first type is pseudostratified epithelium. A B Pseudostratified epithelia are comprised of a single layer of cells attached to the same basement membrane**. The appearance is stratified because this epithelium is made up of several different types of cells of varying heights that become superimposed over each other. B Examples of location: • Upper respiratory tract (most commonly) (This will be covered in detail in Block 2.) ORIENT YOURSELF: The image at right shows an example of pseudostratified epithelium of the trachea. **All epithelia rest on a layer of tissue called basement membrane (details later). For now, know that the layer of cells in every simple epithelium and the deepest layer of a stratified epithelium attach to a basement membrane. A cell 55 BACK 2.5 Epithelia – Types – Pseudostratified A We mentioned earlier that there are 2 other types of epithelia that are NOT described as simple or stratified. The first type is pseudostratified epithelium. A B Pseudostratified epithelia are comprised of a single layer of cells attached to the same basement membrane**. The appearance is stratified because this epithelium is made up of several different types of cells of varying heights that become superimposed over each other. B Examples of location: • Upper respiratory tract (most commonly) (This will be covered in detail in Block 2.) ORIENT YOURSELF: The image at right shows an example of pseudostratified epithelium of the trachea. **All epithelia rest on a layer of tissue called basement membrane (details later). For now, know that the layer of cells in every simple epithelium and the deepest layer of a stratified epithelium attach to a basement membrane. A cell 56 BACK 2.6 Epithelia – Types – Transitional The second type of epithelium that is NOT simple or stratified is transitional epithelium. It changes appearance based on distension of the lumen of the organ it lines. It is a specialized stratified epithelium. Location: • Unique to the urinary system (bladder, ureter, urethra, etc) and appears different depending on whether the organ it lines is full or empty. When the organ is distended (full), the epithelium resembles a simple squamous epithelium. When the organ is empty or relaxed, the epithelium will appear stratified and cuboidal. One key feature of a transitional epithelium in a relaxed state is a “scalloped” appearance of the lumenal layer of cells. (We will go into more detail in Blocks 2 and 3.) ORIENT YOURSELF: The top image shows the entire wall of a full urinary bladder including its transitional epithelium , which appears very flat because it is distended (full). The arrow is on the lumen (space within the bladder). The bottom image shows a portion of the wall of an empty urinary bladder. Notice the appearance of the epithelium, it looks stratified cuboidal. 57 BACK 3. Epithelia – Cell Surfaces Epithelial cells are very close to one another and must remain in tight proximity. Thus, there are structures between the cells that keep them “attached.” The figure represents 2 epithelial cells. Here we can see a simple cuboidal epithelium, but these concepts apply to all epithelia. ORIENT YOURSELF: • Notice that the epithelial cells are “on top” of another tissue, this is connective tissue – we call it the basement membrane. (More on this later.) • The space at the top of the figure would be an opening or space, called the cavity. It is lined by epithelial cells. If these cells were in the GI tract, the space would be the lumen of the GI tract. The epithelial cells have 3 sides: 1. Apical or lumenal surface (this particular figure shows finger-like projections, called cilia or microvilli – depending on their size – but NOT all epithelial cells have these) 2. Lateral surface 3. Basal surface Underlying connective tissue. 58 BACK 3. Epithelia – Cell Surfaces Epithelial cells are very close to one another and must remain in tight proximity. Thus, there are structures between the cells that keep them “attached.” The figure represents 2 epithelial cells. Here we can see a simple cuboidal epithelium, but these concepts apply to all epithelia. ORIENT YOURSELF: • Notice that the epithelial cells are “on top” of another tissue, this is connective tissue – we call it the basement membrane. (More on this later.) • The space at the top of the figure would be an opening or space, called the cavity. It is lined by epithelial cells. If these cells were in the GI tract, the space would be the lumen of the GI tract. The epithelial cells have 3 sides: 1. Apical or lumenal surface (this particular figure shows finger-like projections, called cilia or microvilli – depending on their size – but NOT all epithelial cells have these) 2. Lateral surface 3. Basal surface Underlying connective tissue. 59 BACK 3. Epithelia – Cell Surfaces Epithelial cells are very close to one another and must remain in tight proximity. Thus, there are structures between the cells that keep them “attached.” The figure represents 2 epithelial cells. Here we can see a simple cuboidal epithelium, but these concepts apply to all epithelia. ORIENT YOURSELF: • Notice that the epithelial cells are “on top” of another tissue, this is connective tissue – we call it the basement membrane. (More on this later.) • The space at the top of the figure would be an opening or space, called the cavity. It is lined by epithelial cells. If these cells were in the GI tract, the space would be the lumen of the GI tract. The epithelial cells have 3 sides: 1. Apical or lumenal surface (this particular figure shows finger-like projections, called cilia or microvilli – depending on their size – but NOT all epithelial cells have these) 2. Lateral surface 3. Basal surface Underlying connective tissue. 60 BACK 3. Epithelia – Cell Surfaces Epithelial cells are very close to one another and must remain in tight proximity. Thus, there are structures between the cells that keep them “attached.” The figure represents 2 epithelial cells. Here we can see a simple cuboidal epithelium, but these concepts apply to all epithelia. ORIENT YOURSELF: • Notice that the epithelial cells are “on top” of another tissue, this is connective tissue – we call it the basement membrane. (More on this later.) • The space at the top of the figure would be an opening or space, called the cavity. It is lined by epithelial cells. If these cells were in the GI tract, the space would be the lumen of the GI tract. The epithelial cells have 3 sides: 1. Apical or lumenal surface (this particular figure shows finger-like projections, called cilia or microvilli – depending on their size – but NOT all epithelial cells have these) 2. Lateral surface 3. Basal surface Underlying connective tissue. 61 BACK 3. Epithelia – Cell Surfaces Epithelial cells are very close to one another and must remain in tight proximity. Thus, there are structures between the cells that keep them “attached.” The figure represents 2 epithelial cells. Here we can see a simple cuboidal epithelium, but these concepts apply to all epithelia. ORIENT YOURSELF: • Notice that the epithelial cells are “on top” of another tissue, this is connective tissue – we call it the basement membrane. (More on this later.) • The space at the top of the figure would be an opening or space, called the cavity. It is lined by epithelial cells. If these cells were in the GI tract, the space would be the lumen of the GI tract. The epithelial cells have 3 sides: 1. Apical or lumenal surface (this particular figure shows finger-like projections, called cilia or microvilli – depending on their size – but NOT all epithelial cells have these) 2. Lateral surface 3. Basal surface Underlying connective tissue. 62 BACK 3.1 Epithelia – Cell Surfaces – Lateral Surface Epithelial cells have 3 surfaces. The apical or lumenal surface is closest to the lumen. The basal surface is closest to the connective tissue underlying the epithelium. The lateral surface is where the cell junctions are located. The lateral surface of epithelial cells contains cell junctions that attach contiguous epithelial cells to one another. In histology these junctions are classified as “stronger” and “weaker”: 1. Stronger junctions hold cells tightly together; they are called anchoring junctions. There are 2 types of these: - Zonulae adherentes - Desmosomes 2. Weaker junctions assist in holding cells together. There are 2 types of these: - Tight junctions (the choice of words is confusing… but that is what they are called…) - Gap junctions Underlying connective tissue. The following slides elaborate on both strong and weak junctions. 63 BACK 3.1 Epithelia – Cell Surfaces – Lateral Surface Epithelial cells have 3 surfaces. The apical or lumenal surface is closest to the lumen. The basal surface is closest to the connective tissue underlying the epithelium. The lateral surface is where the cell junctions are located. The lateral surface of epithelial cells contains cell junctions that attach contiguous epithelial cells to one another. In histology these junctions are classified as “stronger” and “weaker”: 1. Stronger junctions hold cells tightly together; they are called anchoring junctions. There are 2 types of these: - Zonulae adherentes - Desmosomes 2. Weaker junctions assist in holding cells together. There are 2 types of these: - Tight junctions (the choice of words is confusing… but that is what they are called…) - Gap junctions Underlying connective tissue. The following slides elaborate on both strong and weak junctions. 64 BACK 3.1 Epithelia – Cell Surfaces – Lateral Surface Epithelial cells have 3 surfaces. The apical or lumenal surface is closest to the lumen. The basal surface is closest to the connective tissue underlying the epithelium. The lateral surface is where the cell junctions are located. The lateral surface of epithelial cells contains cell junctions that attach contiguous epithelial cells to one another. In histology these junctions are classified as “stronger” and “weaker”: 1. Stronger junctions hold cells tightly together; they are called anchoring junctions. There are 2 types of these: - Zonulae adherentes - Desmosomes 2. Weaker junctions assist in holding cells together. There are 2 types of these: - Tight junctions (the choice of words is confusing… but that is what they are called…) - Gap junctions Underlying connective tissue. The following slides elaborate on both strong and weak junctions. 65 BACK 3.1 Epithelia – Cell Surfaces – Lateral Surface Epithelial cells have 3 surfaces. The apical or lumenal surface is closest to the lumen. The basal surface is closest to the connective tissue underlying the epithelium. The lateral surface is where the cell junctions are located. The lateral surface of epithelial cells contains cell junctions that attach contiguous epithelial cells to one another. In histology these junctions are classified as “stronger” and “weaker”: 1. Stronger junctions hold cells tightly together; they are called anchoring junctions. There are 2 types of these: - Zonulae adherentes - Desmosomes 2. Weaker junctions assist in holding cells together. There are 2 types of these: - Tight junctions (the choice of words is confusing… but that is what they are called…) - Gap junctions Underlying connective tissue. The following slides elaborate on both strong and weak junctions. 66 BACK 3.1.1 Epithelia – Cell Surfaces – Lateral Surface – Zonulae Adherentes Zonulae adherentes (singular: zonula adherens) are a type of “strong” or anchoring cell junctions. Zonula Adherens EPITHELIAL CELL Actin filaments Anchor proteins Cadherins (Ca2+ dependent) EPITHELIAL CELL Anchor proteins Actin filaments Zonulae adherentes have the structure represented above and at right: – Notice the green lines in the figure above, they represent transmembrane proteins. They go through the membrane of each epithelial cell, linking the contiguous epithelial cells. These proteins are cadherins. They are attached to each cell and link to each other (cadherin to cadherin) in the intercellular space. – Cadherins of each epithelial cell also link to anchor proteins in the cytoplasm, which in turn link to actin filaments of the cytoskeleton of the cell. Thus a zonula adherens has the following 3 components: – Cadherins (transmembrane proteins) – Anchor proteins – Actin filaments (these are really part of the cytoskeleton of the cell, but they contribute to the zonula adherens) Underlying connective tissue. Zonulae adherentes tend to be close to the apical surface, but are still on the lateral surface. 67 BACK 3.1.2 Epithelia – Cell Surfaces – Lateral Surface – Desmosomes Desmosomes are the other type of “strong” or anchoring cell junctions. Desmosome EPITHELIAL CELL Keratin filaments Anchor proteins Cadherins (Ca2+ dependent) EPITHELIAL CELL Anchor proteins Keratin filaments Desmosomes have very similar structure to the zonulae adherentes: – Cadherins (transmembrane proteins) – Anchor proteins BUT instead of actin filaments they have – Keratin filaments, also called intermediate filaments Keratin is much stronger than actin; thus, desmosomes are stronger than zonulae adherentes. Desmosomes are described as forming button-like junctions. They tend to be positioned near a zonula adherens, although towards the basal surface of the cell; but still on the lateral surface. Underlying connective tissue. CLICK HERE FOR A CLOSER VIEW OF A DESMOSOME. 68 BACK 3.1.2 Epithelia – Cell Surfaces – Lateral Surface – Desmosomes Desmosomes are consist one of the of “strong” or anchoring cell junctions. Desmosomes oftypes 3 components: Desmosome Cadherin molecules (CAMs) are in the lateral plasma membranes EPITHELIAL CELLcells; they CELLthe narrow of the adjacent bind to oneEPITHELIAL another across Cadherins intercellular space. in the figure. Anchor These are green Keratin Anchor Keratin filaments proteins proteins filaments (Ca2+ dependent) Anchor proteins are located on the cytoplasmic face of the lateral plasma membrane of the cells; they to the Desmosomes have veryadjacent similar structure toconnect the cadherin molecule. These are yellow in the figure. zonulae adherentes: – Cadherins (trans-membrane proteins) Keratin filaments (intermediate filaments) attach to the anchor – anchor proteins. Theseproteins are blue in the figure. – BUT instead of actin filaments they have keratin filaments (also called intermediate filaments). Keratin is much stronger than actin thus desmosomes are stronger than zonulae adherentes. Desmosomes are described as forming button-like junctions. They tend to be positioned near a zonula adherens but towards the basal surface of the cell (still on the lateral surface though). Underlying connective tissue. CLICK HERE FOR A CLOSER VIEW OF A DESMOSOME. 69 BACK 3.1.3 Epithelia – Cell Surfaces – Lateral Surface – Tight Junctions Tight junctions are “weak” cell junctions. Tight Junction EPITHELIAL CELL EPITHELIAL CELL Transmembrane protein Transmembrane protein (Ca2+ dependent) Tight junctions Tight junctions are formed when the extracellular domains of transmembrane proteins (on the lateral surfaces of adjacent cells) interlock with the help of calcium. Some membrane structures (ie, ion channels) are found only on the apical surface or only on the basolateral surface. Tight junctions help keep these structures on the proper surface, thus maintaining the polarization of the cell. Tight junctions can block the passage of lumenal content between cells. Underlying connective tissue. The cytoskeleton of the cell does NOT contribute to tight junctions. 70 BACK 3.1.4 Epithelia – Cell Surfaces – Lateral Surface – Gap Junctions Gap junctions are the other type of “weak” cell junctions. Gap Junction EPITHELIAL CELL EPITHELIAL CELL Connexon Gap junctions Gap junctions are formed by transmembrane proteins, called connexins. Many connexin protein chains form a connexon. Gap junctions create a channel whereby cytoplasm and its water-soluble contents can flow between cells to couple the cells metabolically and electrically. The cytoskeleton of the cell does NOT contribute to the structure of gap junctions. Underlying connective tissue. 71 BACK 4. Epithelia – Basement Membrane All epithelia rest on a layer of connective tissue, called the basement membrane. The basement membrane (BM) is a thin fibrous connective tissue layer between the epithelium and the underlying supporting tissue . All epithelia are avascular (ie, they contain NO blood vessels). In order to receive nutrition from the blood, epithelia rest superficial to a layer of supporting tissue which contains blood vessels. The basement membrane is between the epithelium and the supporting connective tissue. Blood vessels do NOT penetrate the basement membrane; however, it allows transudate (fluid leaked out of the vasculature) to serve the cells of the overlying epithelium. The basement membrane controls permeability to and from the epithelium. Nerves course through underlying tissue and must penetrate the basement membrane in order to innervate the epithelium. Thus, nerves do penetrate the basement membrane. Another very important function of the basement membrane is that it controls epithelial growth, impeding the epithelium from growing “downward.” In malignant growth, the epithelium crosses over the basement membrane. 72 BACK 4. Epithelia – Basement Membrane All epithelia rest on a layer of connective tissue, called the basement membrane. The basement membrane (BM) is a thin fibrous connective tissue layer between the epithelium and the underlying supporting tissue . All epithelia are avascular (ie, they contain NO blood vessels). In order to receive nutrition from the blood, epithelia rest superficial to a layer of supporting tissue which contains blood vessels. The basement membrane is between the epithelium and the supporting connective tissue. Blood vessels do NOT penetrate the basement membrane; however, it allows transudate (fluid leaked out of the vasculature) to serve the cells of the overlying epithelium. The basement membrane controls permeability to and from the epithelium. Nerves course through underlying tissue and must penetrate the basement membrane in order to innervate the epithelium. Thus, nerves do penetrate the basement membrane. Another very important function of the basement membrane is that it controls epithelial growth, impeding the epithelium from growing “downward.” In malignant growth, the epithelium crosses over the basement membrane. 73 BACK 4.1 Epithelia – Basement Membrane – Hemidesmosomes Hemidesmosomes link epithelial cells to the basement membrane. Epithelia that experience high abrasive force are reinforced by junctions called hemidesmosomes, which are similar to desmosomes in the lateral surface of adjacent epithelial cells (as previously described). Refer to the previous slide, as we describe the main components of a hemidesmosome: 1- Laminin in the basement membrane 2- Anchor proteins 3- Integrin proteins in the epithelial cells that happen to be attached to keratin of the cytoskeleton of the epithelial cell NOTE: With Light Microssopes basement membranes can be seen if they are thick or if they have been specifically stained. The basement membrane in this image is particularly thick. With EM, the 3 sublayers of a basement membrane can be seen. While the distinction of these constitutes too much detail for our purposes, know that these layers are called: • Lamina lucida • Lamina densa (or basal lamina**) • Lamina fibroreticularis **Some authors refer to the basement membrane as the basal lamina (1 of its 3 sublayers). However, this may lead to confusion, so we will refer to the basement membrane as the basement membrane. 74 BACK 5. Epithelia – Exocrine Glands Exocrine glands are formed by epithelial cells that specialize in secreting some substance to the exterior. Exocrine glands are formed when the cells in an epithelium proliferate and invaginate. The gland has a space in the center called the lumen. The cells closest to the surface, in conjunction with the corresponding lumen, form the duct of the gland . The rest of the gland is the secretory portion . Observe the apical surface of the cells in the gland. Observe the lateral surface of the cells in the gland. Observe the basal surface of the cells in the gland. The gland is surrounded by blood capillaries . 75 BACK 5. Epithelia – Exocrine Glands Exocrine glands are formed by epithelial cells that specialize in secreting some substance to the exterior. Exocrine glands are formed when the cells in an epithelium proliferate and invaginate. The gland has a space in the center called the lumen. The cells closest to the surface, in conjunction with the corresponding lumen, form the duct of the gland . The rest of the gland is the secretory portion . Observe the apical surface of the cells in the gland. Observe the lateral surface of the cells in the gland. Observe the basal surface of the cells in the gland. The gland is surrounded by blood capillaries . 76 BACK 5. Epithelia – Exocrine Glands Exocrine glands are formed by epithelial cells that specialize in secreting some substance to the exterior. Exocrine glands are formed when the cells in an epithelium proliferate and invaginate. The gland has a space in the center called the lumen. The cells closest to the surface, in conjunction with the corresponding lumen, form the duct of the gland . The rest of the gland is the secretory portion . Observe the apical surface of the cells in the gland. Observe the lateral surface of the cells in the gland. Observe the basal surface of the cells in the gland. The gland is surrounded by blood capillaries . 77 BACK 5. Epithelia – Exocrine Glands Exocrine glands are formed by epithelial cells that specialize in secreting some substance to the exterior. Exocrine glands are formed when the cells in an epithelium proliferate and invaginate. The gland has a space in the center called the lumen. The cells closest to the surface, in conjunction with the corresponding lumen, form the duct of the gland . The rest of the gland is the secretory portion . Observe the apical surface of the cells in the gland. Observe the lateral surface of the cells in the gland. Observe the basal surface of the cells in the gland. The gland is surrounded by blood capillaries . 78 BACK 5. Epithelia – Exocrine Glands Exocrine glands are formed by epithelial cells that specialize in secreting some substance to the exterior. Exocrine glands are formed when the cells in an epithelium proliferate and invaginate. The gland has a space in the center called the lumen. The cells closest to the surface, in conjunction with the corresponding lumen, form the duct of the gland . The rest of the gland is the secretory portion . Observe the apical surface of the cells in the gland. Observe the lateral surface of the cells in the gland. Observe the basal surface of the cells in the gland. The gland is surrounded by blood capillaries . 79 BACK 5. Epithelia – Exocrine Glands Exocrine glands are formed by epithelial cells that specialize in secreting some substance to the exterior. Exocrine glands are formed when the cells in an epithelium proliferate and invaginate. The gland has a space in the center called the lumen. The cells closest to the surface, in conjunction with the corresponding lumen, form the duct of the gland . The rest of the gland is the secretory portion . Observe the apical surface of the cells in the gland. Observe the lateral surface of the cells in the gland. Observe the basal surface of the cells in the gland. The gland is surrounded by blood capillaries . 80 BACK 5.4 Epithelia – Exocrine Glands – Type of Secretion Exocrine glands are classified in a number of ways according to the: 1- Shape of the duct 2- Shape of the secretory portion 3- Mode of secretion 4- Type of secretion Finally, exocrine glands are classified, as the following, according to the type of secretion: •Mucous glands – secrete mucus, which is rich in mucigens (large glycosolated proteins that absorb water and, as a result, produce a thick gel-like material). •Serous glands – secrete a viscous fluid rich in proteins (that are often enzymes) not as thick as mucus. Other exocrine glands are specialized in secreting substances like sweat (sweat glands), sebum/oil (sebaceous glands), or milk (mammary glands). (We will cover these in more detail as we proceed through the different systems in Blocks 2 and 3.) In general with use of H&E, serous cells stain darker than mucous cells . The exact shade of color is dependent on the sample, as there can be variations – depending on the composition of the secretion, and on the degree in which the sample “takes the stain in.” In this course, we will give you examples that are clearly lighter (for mucous cells) and clearly darker (for serous cells). 81 BACK 5.4 Epithelia – Exocrine Glands – Type of Secretion Exocrine glands are classified in a number of ways according to the: 1- Shape of the duct 2- Shape of the secretory portion 3- Mode of secretion 4- Type of secretion Finally, exocrine glands are classified, as the following, according to the type of secretion: •Mucous glands – secrete mucus, which is rich in mucigens (large glycosolated proteins that absorb water and, as a result, produce a thick gel-like material). •Serous glands – secrete a viscous fluid rich in proteins (that are often enzymes) not as thick as mucus. Other exocrine glands are specialized in secreting substances like sweat (sweat glands), sebum/oil (sebaceous glands), or milk (mammary glands). (We will cover these in more detail as we proceed through the different systems in Blocks 2 and 3.) In general with use of H&E, serous cells stain darker than mucous cells . The exact shade of color is dependent on the sample, as there can be variations – depending on the composition of the secretion, and on the degree in which the sample “takes the stain in.” In this course, we will give you examples that are clearly lighter (for mucous cells) and clearly darker (for serous cells). 82 BACK 6. Epithelia – Endothelium and Mesothelium Endothelium (plural: endothelia) and mesothelium (plural: mesothelia) are simple squamous epithelia that are specialized. Remember: simple squamous epithelia are formed by 1 layer of flat cells; and line and cover organs. Endothelium is the simple squamous epithelium lining that is specific to: the walls of the heart, blood vessels (arteries, veins, and capillaries), and lymphatic vessels. Endothelium : Notice that in arteries, veins, and capillaries, the most internal layer (lining) is an endothelium. (Ignore the labels; just focus on the concept.) 83 BACK 6. Epithelia – Endothelium and Mesothelium Endothelia and mesothelia are simple squamous epithelia that are specialized. Remember simple squamous epithelia are formed by one layer of flat cells. Also remember we said epithelia line and cover organs. ****OMIT THIS SLIDE**** Mesothelium is a simple squamous epithelium that covers certain organs in the body and lines internal body cavities. Cells forming mesothelia often secrete a substance called serous (viscous) fluid, thus mesothelia are also referred to as “serous membranes”. Visualize the thoracic cavity lined by a mesothelium. The thoracic wall is internally lined by this tissue which goes on to cover the outer aspect of the organs in the thoracic cavity. Thus the internal thoracic wall, the lungs and heart are covered by this mesothelium. Ask in lab if this is not clear. Mesothelium: ignore the labels and focus on the concept. Notice that the outermost layer (covering) of the ovary (top image) and the lining of the thoracic wall and covering of the lungs (bottom image) are mesothelia. 84 BACK 1. Epithelial Tissue – Introduction Remembering from the module “Introduction to Histological Tissues,” epithelia have abundant cells and a very small amount of extracellular material (ECM) . This is a high magnification (about x600) of the epithelium in the respiratory tract. (Ignore the i.ds in the image.) 85 BACK 1. Epithelial Tissue – Introduction Remembering from the module “Introduction to Histological Tissues,” epithelia have abundant cells and a very small amount of extracellular material (ECM) . This is a high magnification (about x600) of the epithelium in the respiratory tract. (Ignore the i.ds in the image.) 86 BACK 5.2 Epithelia – Exocrine Glands – Shape of the Secretory Portion Exocrine glands are classified in a number of ways according to the: 1- Shape of the duct 2- Shape of the secretory portion 3- Mode of secretion 4- Type of secretion Exocrine glands can be described, as the following, according to the anatomical arrangement of the gland cells – ie, the shape of the secretory portion: •Acinar or alveolar (glands of this type resemble bunches of grapes) •Tubular (glands of this type are simple tube-like, U-shaped portion) Acinar gland. Acinar gland cross-section. ; Tubular gland. In the images, note the difference between a cross-section and a longitudinal section. Tubular gland longitudinal or sagittal section. ; 87 BACK 5.2 Epithelia – Exocrine Glands – Shape of the Secretory Portion Exocrine glands are classified in a number of ways according to the: 1- Shape of the duct 2- Shape of the secretory portion 3- Mode of secretion 4- Type of secretion Exocrine glands can be described, as the following, according to the anatomical arrangement of the gland cells – ie, the shape of the secretory portion: •Acinar or alveolar (glands of this type resemble bunches of grapes) •Tubular (glands of this type are simple tube-like, U-shaped portion) Acinar gland. Acinar gland cross-section. ; Tubular gland. In the images, note the difference between a cross-section and a longitudinal section. Tubular gland longitudinal or sagittal section. ; 88 BACK 6. Epithelia – Endothelium and Mesothelium Endothelium (plural: endothelia) and mesothelium (plural: mesothelia) are simple squamous epithelia that are specialized. Remember: simple squamous epithelia are formed by 1 layer of flat cells; and line and cover organs. Mesothelium is a simple squamous epithelium that covers certain organs in the body and lines internal body cavities (lines CAVITIES; NOT organs). Cells forming mesothelia often secrete a substance called serous (viscous) fluid; thus, mesothelia are also referred to as serous membranes. Visualize the thoracic cavity lined by a mesothelium. The thoracic wall is internally lined by this tissue, which goes on to cover the outer aspect of the organs in the thoracic cavity – much like a blanket draping over the organs. Thus, the internal thoracic wall, the lungs, and heart are all covered by this mesothelium. Similarly, organs in the abdomen and pelvis are covered by a mesothelium. (If this is not clear, ask in lab.) The image at top shows a portion of an ovary – the pink part is the organ, the whitish-blue portion on the right side of the image is the pelvic cavity. Notice that the outermost layer (covering) of the ovary is a mesothelium . The bottom figure illustrates the location of mesothelium lining the thoracic wall and covering the lungs (real images shown in lab). (Ignore the labels; just focus on the concept.) Image: www.faculty.une.edu 89 BACK 6. Epithelia – Endothelium and Mesothelium Endothelium (plural: endothelia) and mesothelium (plural: mesothelia) are simple squamous epithelia that are specialized. Remember: simple squamous epithelia are formed by 1 layer of flat cells; and line and cover organs. Mesothelium is a simple squamous epithelium that covers certain organs in the body and lines internal body cavities (lines CAVITIES; NOT organs). Cells forming mesothelia often secrete a substance called serous (viscous) fluid; thus, mesothelia are also referred to as serous membranes. Visualize the thoracic cavity lined by a mesothelium. The thoracic wall is internally lined by this tissue, which goes on to cover the outer aspect of the organs in the thoracic cavity – much like a blanket draping over the organs. Thus, the internal thoracic wall, the lungs, and heart are all covered by this mesothelium. Similarly, organs in the abdomen and pelvis are covered by a mesothelium. (If this is not clear, ask in lab.) The image at top shows a portion of an ovary – the pink part is the organ, the whitish-blue portion on the right side of the image is the pelvic cavity. Notice that the outermost layer (covering) of the ovary is a mesothelium . The bottom figure illustrates the location of mesothelium lining the thoracic wall and covering the lungs (real images shown in lab). (Ignore the labels; just focus on the concept.) Image: www.faculty.une.edu 90 BACK 5.5 Epithelia – Exocrine Glands – Adenocarcinoma Tumors developing from glandular epithelium are called adenocarcinomas. Because there are epithelial glands in many organs – such as the stomach, uterus, colon, pancreas, liver, prostate, breast, and thyroid – we refer to adenocarcinomas in these organs when the epithelial cells in their respective glands become neoplastic. In some adenocarcinomas, the epithelial cells have a fairly normal morphology; but they secrete abnormal amounts of mucus. In other adenocarcinomas, the epithelial cells form very atypical glands that have abnormal cell morphology. •Normal glandular epithelium in the endocervix •Adenocarcinoma (Observe the difference in the glandular epithelial cells; don’t worry about the details at this point, you’ll learn them next year, just focus on the concept for now). 91 BACK 5.5 Epithelia – Exocrine Glands – Adenocarcinoma Tumors developing from glandular epithelium are called adenocarcinomas. Because there are epithelial glands in many organs – such as the stomach, uterus, colon, pancreas, liver, prostate, breast, and thyroid – we refer to adenocarcinomas in these organs when the epithelial cells in their respective glands become neoplastic. In some adenocarcinomas, the epithelial cells have a fairly normal morphology; but they secrete abnormal amounts of mucus. In other adenocarcinomas, the epithelial cells form very atypical glands that have abnormal cell morphology. •Normal glandular epithelium in the endocervix •Adenocarcinoma (Observe the difference in the glandular epithelial cells; don’t worry about the details at this point, you’ll learn them next year, just focus on the concept for now). 92