Epithelial Tissue

I. The Basic Tissues
The first of the basic tissues we will be discussing is epithelia, the simplest of the four basic tissues. It can develop from ectoderm, mesoderm, or endoderm. The other basic tissues are connective tissue, muscle tissue, and nervous tissue, which we will consider in subsequent lectures.

II. Epithelial Tissue
There are two major subdivisions of epithelial tissue:
—Epithelial membranes (usually referred to simply as epithelia)
These are continuous sheets of cells that cover outer surfaces or line internal surfaces.
—Epithelial glands
Glands develop when epithelia invaginate into underlying connective tissue and differentiate into secretory units.

III. Epithelial Membranes
An epithelial membrane consists of a continuous sheet of cells, one or more layers thick, which is attached to the underlying connective tissue by a basement membrane. The cells are joined together at specialized regions called cell junctions. An important point to remember is that epithelia do not contain blood vessels. Nutrients and oxygen reach epithelial membranes by diffusing from blood vessels located in the connective tissue beneath the basement membrane.

A. Functions of epithelia
Epithelia serve essentially three different functions, depending on their particular specializations:
—Protection (e.g., skin)
—Absorption (e.g., intestinal lining)
—Secretion (e.g., stomach lining)

B. Types of epithelia
There are three types of epithelia, each distinguished by the number of cell layers comprising the epithelial membrane:
— Simple has one layer of cells.
— Stratified has two or more layers of cells.
— Pseudostratified has one layer of cells, but appears stratified because cells are of different heights. Nevertheless, all cells are in contact with the basement membrane.

C. Simple epithelia
By virtue of their structure, simple epithelia are suited for absorption and secretion. They are classified according to the shape of the constituent cells:
—Simple squamous has a single layer of flattened cells (e.g., mesothelium of body cavities and endothelium of blood vessels).
—Simple cuboidal has single layer of cube-shaped cells (e.g., collecting tubules of kidney).
—Simple columnar has single layer of tall, column-shaped cells. This type of epithelium often contains absorptive cells interspersed with secretory cells. In the small intestine, for example, there are secretory cells called goblet cells which secrete mucus. The absorptive cells, on the other hand, have microvilli on their luminal surfaces to facilitate absorption of nutrients. Collectively, these microvilli give rise to the striated border visible in the light microscope. In some cases, the columnar cells maybe ciliated with goblet cells interspersed in between (e.g., some parts of the lower respiratory tract). And in the case of the stomach lining, all of the columnar cells are mucus-secreting.

D. Stratified epithelia
Due to multiple layers of cells, stratified epithelia are well-suited for protection.
—Stratified squamous has multiple layers of cells, the outermost layer of which contains squamous cells. There are two varieties: nonkeratinized (e.g., lining of vagina) and keratinized, in which the superficial cell layers have been transformed into a hard layer of nonliving keratin (e.g., epidermis of skin).
—Stratified cuboidal usually has two or three layers of cuboidal cells. This type of epithelium is largely confined to the lining of large ducts.
—Stratified columnar has several cell layers, the outermost of which contains columnar cells. This type of epithelium is relatively rare, but is found in some large ducts and a few other places.
—Transitional is similar to stratified squamous epithelium (nonkeratinized variety), except that the outermost cell layer consists of large, rounded cells that are often polyploid or binucleate (e.g., lining of urinary bladder).

E. Pseudostratified epithelia
—Pseudostratified ciliated columnar
All cells lie in contact with the basement membrane, but not all cells reach the epithelial surface. This gives the illusion of several cell layers, but is actually only one cell layer. The taller cells that reach the epithelial surface are either ciliated cells or goblet cells. Those that don't reach the surface are basal cells, which serve as stem cells for the others. This type of epithelium lines most of the upper respiratory tract. In the ductus epididymis of the male, however, the epithelium consists of pseudostratified columnar cells that lack true cilia and have nonmotile stereocilia instead. The epithelium here also lacks goblet cells.

IV. Cell Junctions
There are three types of cell junctions found in epithelia: (1) tight junctions, which are found only in epithelia, (2) adhering junctions, and (3) gap junctions. Both adhering and gap junctions are found in other tissues as well.

A. Tight junctions
In tight junctions, the membranes of contiguous cells are fused together along a system of surface ridges, thereby occluding the intercellular space. Often, the tight junction forms a belt around the cell perimeter, near the apical (luminal) surface. This is called a zonula occludens. Zonula occludens form a complete, tight seal and prevent the passage of material across the epithelium (e.g., macromolecules are prevented from passing from the intestinal lumen into the intercellular space). Sometimes a tight junction is restricted to specific areas of the cell perimeter, thereby forming an incomplete seal. This is called a fascia occludens (e.g., the endothelium of blood vessels).

B. Adhering junctions
There are two types of adhering junctions: (1) zonula adherens and (2) macula adherens.
—The zonula adherens is a belt-like junction extending around the perimeter of the cell. It is located just below the zonula occludens on the lateral aspect of contiguous cells. The intercellular gap between adjoining cells is filled with a filamentous material. The zonula adherens is also the site for the attachment of a circumferential band of microfilaments located just deep to the membrane.
—The macula adherens—also called a desmosome —is a small, circular junction located just below the zonula adherens. It represents a series of button-like junctions scattered around the cell perimeter in an uneven row. Electron-dense plaques are seen on either side of the opposed membranes. These plaques serve as attachment sites for bundles of tonofilaments (a type of intermediate filament). Running between the two plaques is a fine electron-dense line, which is thought to represent transmembrane linkers extending across the intercellular gap. Hemidesmosomes (half-desmosomes) are seen between epithelial cells and the underlying basement membrane to which they are attached. Together, the zonula occludens, zonula adherens, and macula adherens constitute the junctional complex visible in the electron microscope. In the light microscope, the junctional complex is seen as the terminal bar.

C. Gap junctions
Gap junctions are essentially communications junctions consisting of small, circular regions of opposed cell membranes with a narrow gap in between. The gap is bridged by tiny tubular channels that allow passage of ions and various small molecules from cell-to-cell. These channels are called connexons and are thought to represent transmembrane proteins that interlock across the narrow gap. Thus, gap junctions permit direct cell-to-cell transfer of low molecular weight nutrients and intracellular messengers like cAMP, as well as maintain electrical coupling between cells. Gap junctions are also called nexuses.

V. The Terminal Web
Just beneath the striated border of intestinal epithelial cells is a horizontal network of microfilaments, intermediate filaments, and spectrin, which acts to stabilize the filaments. Some myosin is present, too, which provides contractile properties. This region is called the terminal web. The microfilaments from the microvilli and zonula adherens, as well as the tonofilaments from the desmosomes, all intermingle to some degree within the terminal web.

VI. Epithelial Glands
There are two types of glands derived from epithelia: exocrine glands and endocrine glands.
All exocrine glands consist of two components: (1) groups of specialized cells called secretory units that produce the characteristic secretions, and (2) tubular ducts that convey these secretions onto an epithelially-covered surface.

A. Classification of exocrine glands
Based on number of ducts
—Simple gland has a single unbranched duct (e.g., sweat gland).
—Compound gland has a branched duct system (e.g., pancreas).

Based on shape of secretory unit
—Tubular gland, the secretory unit is tube-shaped.
—Alveolar (acinar) gland, the secretory unit is rounded.
—Tubuloalveolar gland, both types of secretory units are present.

Based on composition of secretion
—Serous gland, which secretes enzymes in a watery fluid (e.g., parotid gland).
—Mucous gland, which secretes a viscous glycoprotein called mucus (e.g., sublingual gland).
—Mixed (seromucous) gland, in which both types of secretion are produced in the same gland because it contains both serous and mucous cells (e.g., submandibular gland). In H & E sections, serous cells exhibit the following features: The base of the cell contains a large, spherical nucleus, and the surrounding cytoplasm appears intensely basophilic due to an abundance of RER. The apical end of the cell contains numerous eosinophilic zymogen granules filled with secretory enzymes. In contrast, mucous cells in H & E sections appear differently: The base of the cell contains a flattened nucleus, and the cytoplasm appears pale and vacuolated due to an abundance of secretory granules containing mucin. This mucin can be visualized by the PAS-stain. When mucin is released from the cell, it becomes hydrated to form mucus. Mixed glands consist of both serous and mucous secretory units, as well as secretory units that contain both serous and mucous cells. Such mixed secretory units are composed mostly of mucous cells, with a small "cap" of serous cells called a serous demilune. Both cell types secrete into the same lumen. Surrounding each secretory unit are the processes of a myoepithelial cell, which cradle the unit like a loose "basket". Contraction of myoepithelial cells expels the secretions into the duct system.

Based on mode of secretion
—Merocrine gland. Secretion occurs via exocytosis. This is the most common method (e.g., pancreas).
—Holocrine gland. The entire cell and its contents form the secretory product. For example, in the sebaceous gland, cells in the basal portion of the gland are displaced into the interior regions as new cells arise in the lining layer. The displaced cells, deprived of their proximity to the blood supply, begin to degenerate and accumulate lipid. Eventually, the disintegrated cells emerge from the gland as oily sebum.
—Apocrine gland. The apical portion of the cell membrane and associated cytoplasm are expelled as the secretory product. However, this concept is now largely considered to be incorrect. Most glands which were once thought to secrete by this mechanism are now known to secrete via merocrine secretion. The only gland which might secrete via apocrine secretion is the mammary gland.

B. Organization of exocrine glands
There are two major components of any exocrine gland:
—Parenchyma, which is the epithelial component of the gland consisting of the secretory units and ducts.
—Stroma, which is the connective tissue component of the gland (for support), as well as blood vessels and nerves.
The capsule is fibrous connective tissue that encloses the gland. Septa consist of fibrous connective tissue, continuous with the capsule, that subdivides the parenchyma into lobes (big glands) or lobules (small glands). Such septa are referred to as interlobar or interlobular septa, respectively. Intralobular ducts lie within the parenchyma of the lobules. These ducts empty into the interlobular ducts located within the interlobular septa, between the lobules. These, in turn, eventually empty into the main duct leaving the gland. The pathway for exocrine secretions is: alveolus—intercalated duct—intralobular duct—interlobular duct—main duct.

C. Control of exocrine secretion
The process of secretion is regulated by nerve impulses from the autonomic nervous system (both sympathetic and parasympathetic components), as well as by certain hormones.

D. Endocrine glands
Endocrine glands have no ducts, but rather secrete their hormones directly into the bloodstream to produce effects in distant tissues. Groups of secretory cells are therefore situated near capillaries. The gland is surrounded by a connective tissue capsule, projections of which may extend into the gland as trabeculae. In most cases, regulation of endocrine secretion is via negative feedback. We will consider the endocrine system in detail towards the end of the course.