Overview – Epithelia
Plate 2-1. Simple Squamous Epithelium: The Lung
Plate 2-2. Simple Cuboidal Epithelium: The Thyroid Gland
Plate 2-3. Simple Columnar Epithelium: The Intestine
Plate 2-4. Stratified Squamous Epithelium: The Esophagus
Plate 2-5. Pseudostratified Columnar Epithelium: The Trachea
Having introduced cells, we move now to tissues – groups of cells and their products that perform specific functions. The classic tissues – epithelia, nerve, muscle, and connective tissue – are combined to make up the major organs that, taken together, form the organism known as the human body.
The first class of tissue we shall consider is the epithelium. Epithelia cover the body and line the inner and outer surfaces of organs. Although they are supported by connective tissue, they contain none; although they are underlain by capillaries, epithelia are avascular.
Epithelia are organized in a variety of ways, and their spatial organization both permits and reflects their functions. Epithelial nomenclature is straightforward, usually employing two or three words for each descriptive term. The first word tells whether the tissue is made of one cell layer (simple) or of more layers (stratified). The second word describes the shape of the uppermost layer of cells, be they squamous, cuboidal, or columnar. The third word, if any, describes the way in which the uppermost cells are specialized. Some epithelia are specialized by bearing cilia; others, by being filled with the water-resistant protein Keratin. The integument, for example, is covered by a stratified squamous keratinized epithelium. This name indicates that skin consists of several cell layers, the uppermost cells of which are flat and filled with Keratin.
Because form follows function in biologic systems – a recurring theme in the study of microanatomy – epithelia adopt specific forms in order to perform specific functions. Given that epithelia are surfaces, one can, as a simple exercise in armchair bioengineering, list the possible functions a biological surface can perform, design a cellular surface capable of performing each function, and generate the actual epithelial classes that organs do have in the human body.
Among these functions is the ability of a cellular surface to selectively transport substances across itself. In addition, it can elaborate and secrete materials; conversely, it can absorb materials from its surroundings. Furthermore, a biologic surface can protect its contents from water loss, physical damage, and the like; and it can move materials along itself. These functions differ from one another and call for a variety of cellular designs. In the lungs, where gas exchange occurs, and in capillaries, which supply nutrients and gases to all cells of the body, rapid transport of materials is essential. These organs need a single thin layer of flat cells – a simple squamous epithelium. Active Transport of materials, on the other hand, requires more metabolic machinery, necessitating a single layer of cells with more bulk to house the cytoplasmic organelles that do the work. Consequently, simple cuboidal epithelia often constitute surfaces such as those in the kidney that actively transport molecules and ions against a concentration gradient. Secretory surfaces, too, require large cells that contain the cytoplasmic machinery required to synthesize and package proteins, glycoproteins, and other macromolecules for export. Consequently, most secretory surfaces consist of a single layer of large cells – either a simple cuboidal or simple Columnar Epithelium. The same holds true for absorptive epithelia; they need space to house the organelles required to process materials taken up into the cell.
Protective surfaces, however, face a different set of problems. They must place a layer of tough, waterproof, expendable cells at the epithelial surface and provide for their periodic replacement. This requirement calls for a stratified Squamous Epithelium, in which flattened surface cells (Squames) are periodically shed and replaced by mitotic activity and differentiation of other underlying cells.
These and several other examples of the ways in which form follows function in epithelia are depicted and described in this chapter.
Simple Squamous Epithelium: The Lung
As mentioned in the overview, epithelia are cellular linings or coverings. Of these, perhaps none are thinner or more delicate than the simple squamous epithelia that line the lungs and capillaries. Figures A and B are a matched pair of light and electron micrographs of serial sections taken through the monkey lung that clearly show the super-thin nature of the epithelia that line the alveoli of the lungs and the capillaries that course through them.
The lung is designed to move material across its borders rapidly. In an average day of rest, a person’s lungs exchange some 550 L (138 gal; 17 ft â ‰ ¥) of oxygen and carbon dioxide between blood and the atmosphere. This extremely rapid and efficient gas exchange is facilitated by the design of the thin, gossamer-like epithelium lining the lung’s airspaces, or alveoli, and their associated capillaries.
Both Alveolus and capillary are lined by a single layer of flat cells that provide an excellent example of simple Squamous Epithelium. Figures A and B at right are light and electron micrographs of sections taken through an Interalveolar Septum – a wall separating two adjacent alveoli – in the lung of the macaque. Here, the air-filled alveolar spaces (A) lie above and below the interalveolar Septum itself (S). The lung, of course, is highly vascular, and many capillaries (C) supply the Interalveolar Septum with blood. Although details of its construction are not evident by light microscopy (Figure A), the extreme flatness of the Interalveolar Septum‘s simple squamous epithelia is nevertheless apparent. The barrier interposed between blood and air can be as thin as 0.15um, approaching the limit of resolution of the light microscope. When the area enclosed within the circle is viewed by electron microscopy, as in Figure B, one can see that the wall of the Septum is actually two cell layers thick – each layer consisting of the simple squamous epithelium lining the Alveolus and the simple squamous epithelium lining the adjacent capillary. This construction is evident in the area indicated by the arrow. Here, the two epithelia have pulled apart and are seen to be separated by an artifactual space in which splayed connective tissue fibrils (CT) are evident. The prominent Nucleus (N) helps to identify the capillary endothelial cell to which it belongs.
The epithelial cells that line capillaries are routinely referred to as endothelial cells, and the capillary epithelium is called an Endothelium – a term reserved for the layer of flat cells lining blood vessels, lymph vessels, and other cavities. A structure called the basement membrane underlies the capillary Endothelium as with all epithelia. The Basement Membrane varies in thickness. In some epithelia it is visible by light microscopy. When viewed with the electron microscope, the Basement Membrane is seen to consist of a thin, amorphous feltwork, some 500 to 800 â ‰ ˆ thick, called the Basal Lamina, closely associated with small bundles of reticular fibers embedded in a protein-Polysaccharide Ground Substance. As its name suggests, the basement membrane always covers the bottom of an epithelium and separates the epithelium from the structures that it overlies.
Figures A & B
Figures A and B. Matched pair of light and electron micrographs of nearly serial sections taken through the lung of the macaque. A, alveolar space; B, (Figure B only) Basement Membrane; C, capillary; CT, connective tissue fibrils (Figure B only); E, Erythrocyte; N, Nucleus of capillary endothelial cell; S, Interalveolar Septum; 1, alveolar epithelium; 2, capillary epithelium (Endothelium); circle, attenuated region of interalveolar Septum; arrow, artifactual separation of alveolar and capillary epithelia. Figure A, 2,000 X; Figure B, 8,500 X 26
Simple Cuboidal Epithelium: The Thyroid Gland
As mentioned in the overview, cells engaged in the active biosynthesis or degradation of macromolecules are frequently cuboidal. An epithelium composed of a single layer of such cells, called a simple cuboidal epithelium, is easy to recognize in histological preparations.
Figure A at right is a high-magnification light micrograph of a section taken through the thyroid gland; Figure B is a low-magnification electron micrograph of a corresponding region within the same tissue sample. The thyroid gland, described in Chapter 19, consists of a collection of individual functional units called follicles. Each Follicle is a spherical structure consisting of a central mass of colloidal material (CO) surrounded by a simple Cuboidal Epithelium (E). The epithelial cells elaborate and secrete the Colloid, which contains, among other things, Thyroglobulin – Thyroid Hormone complexed with a carrier protein.
The thyroid gland is an endocrine organ. The hormone it produces, delivered directly into the bloodstream, is borne by the blood to target tissues located at some distance from the organ itself. The thyroid gland is unique among endocrine organs in that it stores large quantities of hormone prior to the hormone’s release into the general circulation. This capacity for storage may have developed in part because Thyroid Hormone molecules contain the element iodine; since iodine is not always present in the mammalian diet, the ability to manufacture excess hormone when iodine is available and to store it for use in times of dietary iodine deficiency may have conferred a selective advantage upon animals equipped to do so.
The mechanism of release of Thyroid Hormone is unusual. When called upon by the Hypothalamus to release hormone, the simple Cuboidal Epithelium of the thyroid gland follicles actively takes up tiny droplets of Colloid from the follicular interior by Pinocytosis. Once Thyroglobulin is within the Cytoplasm, the hormone itself – usually diiodothyronine or triiodothyronine – is enzymatically cleaved from the carrier protein and released from the basal pole of the cell. Once free in extracellular space, the hormone diffuses rapidly into the capillaries within the rich vascular bed that underlies the epithelium.
From the discussion above it is evident that the cuboidal cells of the thyroid Follicle are active in the biosynthesis and degradation of macromolecules. Figure B at right shows that this activity is manifest in the cytoplasmic organization of the cells. Around the centrally located nuclei (N), for example, are profiles of many Mitochondria (M) and Cisternae of the rough Endoplasmic Reticulum (RER). The endoplasmic reticulum is active in the synthesis of materials that are packaged within the numerous secretory vesicles (V) that populate the apical pole of the cell. The apical cell surface bears small, finger-like projections called Microvilli(arrow) that amplify the area of the cell membrane available for the exchange of materials in and out of the cell.
Most of the cell components lie close to or beneath the limit of resolution of the light microscope and thus are difficult to detect in Figure A. Although the nuclei (N) are evident by light microscopy, the secretory vesicles (V) and Mitochondria(M) appear only as fuzzy areas of increased density embedded in an amorphous Cytoplasm. One can learn to identify structures barely visible at the level of the light microscope by carefully comparing light micrographs, such as that in Figure A, with electron micrographs of corresponding areas, such as that in Figure B.
Figures A and B. Light and electron micrographs of the simple Cuboidal Epithelium that lines follicles within the thyroid gland. Parts of two adjacent follicles, each with its own epithelium, are shown. CO, Colloid; E, epithelium; M, mitochondrion; N, Nucleus of epithelial cell; RER, rough Endoplasmic Reticulum (Figure B only); V, Secretory Vesicle; arrow, small Microvilli (Figure B only). Figure A, 4,750 X; Figure B, 7,900 X 28
Simple Columnar Epithelium: The Intestine
A simple Columnar Epithelium consists of a single layer of cells in which each cell is taller than it is wide. Considerable variation exists between the height-to-width ratios of cells in different kinds of simple columnar epithelia; consequently, some are described as “low columnar” and others as “high columnar.” Unfortunately, the specificity of terminology is limited. In many cases, low columnar and high cuboidal epithelia are difficult to distinguish from one another.
Figures A and B at right are a matched pair of light and electron micrographs of serial thick (1 Â µm) and thin (800 â ‰ ˆ ) sections taken through the first segment of the small intestine, the duodenum. Here, the intestinal surface is thrown into folds called villi that greatly increase the area of intestinal surface available for absorption of ingested nutrients. In the figures at right, a portion of a Villus (V) that projects into the intestinal lumen (L) has been cut in longitudinal section. The outer surface of the Villus, exposed to the lumen and its contents, is lined by a simple Columnar Epithelium (EP) that rests upon the Lamina Propria (LP). The Lamina Propria is a thin core of loose connective tissue that lends structural support to the Villus. The dotted line marks the boundary where the Basement Membrane of the epithelium makes contact with the Lamina Propria.
The primary function of the epithelium covering the duodenum is the absorption of digested food. Consequently, these epithelial cells are endowed with surface specializations that facilitate transport of nutrients from the lumen of the gut into the cell. Furthermore, the cell possesses a system of cytoplasmic organelles capable of breaking down absorbed materials into molecular components suitable for delivery into the circulatory system which then distributes the components to the body. In Figures A and B, the lumenal surface of the intestine is modified to form a brush border (BB). Also called the Striated Border, the brush border is composed of thousands of tiny, finger-like Microvilli (MV) that provide each cell with a thirtyfold increase in surface area. Beneath the brush border, the apical portion of the lateral surfaces of the cells maintains contact with one another by junctional complexes (arrows) that appear, at low magnification, as dense dots. The Junctional Complex, consisting of a tight junction (Zonula Occludens), an Intermediate Junction (Zonula Adherens), and a Desmosome (Macula Adherens), serves to bind the cells together and prevent direct diffusion of materials from the lumen of the intestine into the intercellular spaces.
At their apical poles, the columnar absorptive cells of the epithelium contain numerous vesicles, Mitochondria (M), and elements of the rough Endoplasmic Reticulum (RER). Above the nuclei, dilated Cisternae of the Golgi apparatus (G, Figure B) are present. In a section cut at right angles to the epithelial surface, as in Figure A, the nuclei (N) are aligned in a single row in the middle of the epithelium; the simple columnar nature of the epithelium is apparent. Unfortunately, sections are frequently not cut at the ideal angle, and the microscopist is faced with that major histological problem – misleading images produced by the plane of section. Were the intestinal epithelium cut in an oblique plane of section, it would appear to contain more than one layer of nuclei, lending a false appearance of stratification to the epithelium. Fortunately, with experience, you will learn to differentiate between true stratified columnar epithelia (which are rare) and obliquely sectioned simple columnar epithelia (which are common).
Figures A and B. Matched pair of light and electron micrographs of serial sections taken through the simple Columnar Epithelium of the duodenum. BB, brush border; EP, epithelium; G, Golgi Apparatus (Figure B only); L, lumen; LP, Lamina Propria (Figure A only); M, Mitochondria (Figure B only); N, nuclei; MV, Microvilli; RER, rough Endoplasmic Reticulum (Figure B only); V, Villus (Figure A only),arrow, Junctional Complex; dotted line, border between epithelium and Lamina Propria. Figure A, 4,000 X; Figure B, 4,300 X 30
Stratified Squamous Epithelium: The Esophagus
Stratified Squamous Epithelium, as the name indicates, is several cell layers thick. Its uppermost layer consists of a sheet of expendable flattened cells that are periodically worn off and shed from the epithelial surface. A typical stratified Squamous Epithelium is depicted in Figures A and B, a matched set of light and electron micrographs of serial thick and thin sections taken through the surface of the esophagus.
The primary function of the esophageal epithelium is protection of underlying tissues from abrasion by the swallowed bolus of food that passes through it rapidly on its journey from mouth to stomach. Consequently, the esophageal epithelium is thick and its upper surface is tough. The flat uppermost cells, called Squames (S), are shed periodically and replaced by cells that migrate upward. New cells are supplied by mitotic activity in the basal layer of cells (B).
In Figures A and B at right, for example, the mitotic activity of the basal cell layer is evident in the condensed chromosomes of a cell caught in the Metaphase of Mitosis (arrow). Whereas the stem cells of the stratum basale are large and rounded, the cells in the overlying strata become progressively flattened. As the cells approach the epithelial surface, their Cytoplasm becomes keratinized. As the process of keratinization proceeds, the number of cytoplasmic organelles decreases, the Nucleus darkens and becomes smaller, and dense granules Keratohyalin Granules (K) become evident. Eventually the surface cells come to contain little other than Keratin; at this point, the cells are flat plates that form a smooth, durable surface along which swallowed food can slide. In the case of rodents, such as the mouse that provided the tissues shown at right, the food in the diet is quite rough. As a result, the superficial cells of the rodent esophageal epithelium become completely keratinized; that is, the superficial Squames have lost their nuclei and are flat plates of Keratin. Consequently, their esophageal epithelium is classified as keratinized stratified Squamous Epithelium. The food eaten by humans and other primates, however, tends to be softer and more hydrated. Consequently, our esophageal epithelium is lined by an epithelium whose surface cells, although filled with Keratin, retain their nuclei. Consequently, human and primate esophageal epithelium is classified as nonkeratinized stratified Squamous Epithelium. The fact that the same epithelium in different animals may be classified in different categories can be a source of confusion, which can be somewhat alleviated by simply looking at the tissue sample and classifying it according to the perception of its histologic organization.
The dramatically different functions of the inner linings of the lung (Plate 2-1) and the esophagus Ã ± i.e., rapid transport of gases as opposed to protection from surface abrasion – are manifest in their dramatically different epithelial organization. Whereas the thickness of the lung’s epithelium measures less than a Micrometer, that of the mouse esophagus shown at left is 65 to 70 Â µm. Human esophageal epithelium is even thicker. Furthermore, the connective tissue that supports the esophageal epithelium, the Lamina Propria (LP), is extensive. Collagen fibrils (F) are evident, as are the cells that make Collagen, the fibroblasts (FB). Tiny capillaries (C) course through the Lamina Propria, as do thin-walled lymph vessels (L).
Figures A and B. Matched pair of light and electron micrographs of cross sections taken through the wall of the esophagus of the mouse. B, basal cell; C, capillary; F, Collagen fibrils; FB, Fibroblast; K, Keratohyalin Granules; L, lymph vessel (Figure A only); LP, Lamina Propria; S, Squames; arrow, dividing cell. Figure A, 1,400 X; Figure B, 1,600 X 32
Pseudostratified Columnar Epithelium: The Trachea
Thus far, we have examined simple epithelia, which consist of a single layer of cells, and a stratified epithelium, which consists of several layers of cells. Now we come to a pseudostratified epithelium – one that looks stratified but is not. A pseudostratified epithelium actually consists of one layer of cells in which each cell makes direct contact with the Basement Membrane.
A single layer of cells can give the false appearance of stratification because in a pseudostratified epithelium, several different cell types, different in height, sit side by side. Their nuclei frequently lie at different levels, and some cells do not reach the epithelial surface. This arrangement is shown clearly in Figures A and B at right – a matched pair of light and electron micrographs of the pseudostratified Columnar Epithelium that lines the trachea of the monkey. Here, the apical surface of the epithelium contacts the tracheal lumen (L); the basal surface rests upon a very well developed and conspicuous Basement Membrane (BM). The tracheal epithelium contains three cell types: ciliated cells (C), goblet cells (G), and Basal Cells (B). The nuclei of these different kinds of cells all lie at different levels, lending a false appearance of stratification to the epithelium. The nuclei of the ciliated cells (N1), for example, lie in the middle of the epithelium, whereas the goblet cells’ nuclei (N2) are pushed down to the base of the cell. The nuclei of the Basal Cells (N3) lie right next to the basement membrane (BM). Why are the cells of the tracheal epithelium arranged in this manner?
The primary function of the trachea is to carry air, large volumes of it every day, from the mouth to the lungs and back out again. Since raw atmospheric air is unsuitable for admission to the lungs, the epithelium of the trachea, along with that of the nasal cavity, must moisten the air, trap airborne particles and bacteria taken in with every breath, and then get rid of the entrapped particles. During all of these operations, the tracheal epithelium must protect itself from drying out. The tracheal epithelium accomplishes these tasks by covering itself with a moving layer of viscous, highly hydrated Mucus. The sticky Mucus traps airborne particles the way flypaper collects flies. All the while, it is protecting the cells beneath from desiccation and is actively moistening the inhaled air. The Mucus needs to be replaced frequently by the goblet cells. After the Mucus is secreted and established on the epithelial surface by the goblet cells, it must be moved up to the mouth to be swallowed or expectorated. This task is accomplished by the ciliated epithelial cells, whose cilia (arrow) beat in a highly coordinated, wavelike fashion (called the Metachronal Wave) with their active strokes directed toward the oral cavity. During the course of life, the ciliated cells and goblet cells of the pseudostratified Columnar Epithelium of the trachea occasionally need to be replaced. Replacements are provided by mitotic activity of the Basal Cells that lie close to the basement membrane.
Figures A and B. Matched pair of light and electron micrographs of serial sections taken through the trachea of the macaque. B, Basal Cells; BM, Basement Membrane; C, ciliated cell; G, Goblet Cell: L, lumen of trachea; N1, Nucleus of ciliated cell; N2, Nucleus of Goblet Cell; N3, Nucleus of basal cell; arrow, cilia that project from surface of ciliated cell. Figure A, 1,750 X; Figure B, 1,750 X