Epithelial Tissue Characteristics

Epithelial tissue or epithelium [the plural form is epithelia] occurs as a sheet of cells to cover an organ surface or line a body cavity. In other cases, epithelial tissue makes up the bulk of the cells in glandular tissues. The covering type of epithelium is abundant and widespread. These are the cells that make up the skin, the internal surfaces of the cardiovascular system, the digestive tract, the reproductive tract, and the respiratory tract. Epithelial tissue also covers internal body cavities. The functional cells of the accessory organs of the digestive system, that is, the liver, pancreas, and gall bladder, are mostly epithelial cells. Other glandular organs, that is, pituitary, adrenal, thyroids, salivary, and so forth, are also composed of epithelial cells. Epithelial cells form boundaries between different regions of the body. For example, the epidermis of the skin creates a protective barrier between the inside and outside of the body. The same is true for the epithelial cells that line the internal surface of the respiratory or digestive tract. Other specialized epithelial cells include reproductive cells (ova and spermatozoa), rods and cones of the retina, taste buds, and others. This explains the many functions attributed to epithelial tissues: (1) protection, (2) absorption, (3) secretion, (4) excretion, (5) filtration, and (6) sensory reception.

Distinctive features also contrast epithelial tissues from the other three tissue types. One of these is the degree of cellularity of the epithelial tissues compared with other tissues. Specifically epithelial tissue is composed of cells that are very tightly packed together so that usually there is a little space between the cells. In fact, for the epithelial cells to successfully complete their roles as protective barriers, adjacent cells form specialized contacts. Epithelial cells acting to absorb or secrete products are described as being polarized. This is most easily visualized for glandular secretory cells. The basal region of the cell (closest to the basement membrane and capillaries) can be thought of as the manufacturing site for the cell. Products to be secreted are packaged and processed in the Golgi for subsequent secretion from the cells in the apical region of the cell (see Fig. 2.8). In other cases, the apical end of the cell (near the free surface) is acting to absorb nutrients or move surface secretions. For example, the cells of the intestinal tract and kidney tubules have extensive microvilli. This markedly increases surface area to improve function. Other epithelial cells are even more specialized with cilia. For example, cells lining the ova duct or the respiratory tract that function to propel substances along their surfaces.

The epithelial cells, however, are not alone in carrying out their activities. The cells are attached to a thin supporting sheet or layer of nonliving material called the basal lamina. This layer is composed of proteins and glycoproteins that are produced by the epithelial cells. In some regions, for example, Bowman’s capsule of the kidney tubules, the basal lamina is particularly thick so that it acts as a filtration barrier to prevent the movement of plasma proteins into the urinary filtrate. Underneath the basal lamina, the reticular lamina appears. This is an additional layer of more fibrous proteins, for example, collagens and elastic, that link the epithelial cells with the connective tissue underneath. These two layers or lamina (basal +reticular) are collectively called the basement membrane. It defines the boundary between the epithelium and the connective tissue or stromal. Interestingly, although there are nerve fibers, that is, sensory nerves that penetrate the epithelium of the skin or intestinal tract, the epithelium is avascular. It does not contain blood vessels. These appear in the loose more open spaces of the connective tissue. This means that both the nutrients that supply the epithelial cells and waste products from the cells depend on diffusion to pass between the tightly packed epithelial cells and the capillaries underneath. This likely explains why it is rare to find epithelial tissue that contains more than a few strata of living cells. A final property is the capacity of epithelial cells for rapid growth and regeneration. Think in your own life, how quickly skin abrasions heal. However, this may have a downside when you consider that most cancers are carcinomas, that is, derived from epithelial cells.

Simple Epithelium

As you will likely experience in a laboratory setting with a microscope and set of slides or in multimedia presentations, tissue samples contain multiple cell types and in the case of epithelial tissues often more than one type of epithelium. This means that while the focus of a particular specimen may be on a specific cell layer, it does not mean this cell or tissue type is exclusive. Our first example (Fig. 4.9) shows epithelial cells growing on the surface of a cell culture dish. These cells have proliferated and arranged themselves into a pavement of cells one cell layer thick. If you imagined these cells growing on a flexible sheet that could be rolled into a tube you would have a simple recreation of a capillary. Regardless, in this view, you are looking directly down onto the surface of the cells. Each cell looks something like a fried egg, with the nucleus the yolk of the egg. The cells are flattened and closely packed together. They would be classified as simple squamous. As another way to visualize simple squamous cells, imagine the flattened floor tiles in a kitchen as single squamous epithelial cells all linked together to make the floor. The grout between the tiles would represent the membrane junction complexes that anchor epithelial cells together and create functional barriers between tissue compartments, that is, the surface and the subflooring underneath. It is typical to find simple squamous epithelium in areas where absorption and filtration occur and a thin barrier is desirable, for example, capillaries or lining of alveoli of the lungs. Can you rationalize why simple squamous would be a poor choice for the surface of the body?

The image shown in Figure 4.10 is from the kidney and is mostly parenchymal tissue. It shows a series of cross‐sectioned tubules from several nephrons. You should remember that epithelial cells are often found on free surfaces, even though some of the surfaces may be very minute internal surfaces, that is, the inside of small vessels or tubules. Some of these tubules are lined by a single layer (simple) of squamous epithelial cells but others are lined by a single layer of cuboidal epithelial cells. Can find examples of each? Perhaps a hint is in order. For many of the squamous epithelial cells, the cytoplasm is very thin so the most prominent feature of the cells is the nucleus, which often seems to protrude into the space of the tubule. Can you pick some of these out of the image?

Figure 4.11 shows a portion of this tissue taken at a higher magnification of 1000×. This is accomplished by the use of the 100× objective lens of the microscope and the 10× eyepiece. This means that the magnification reaching your eye is 1000‐fold. The camera used to take the photographs also utilizes a 10× lens mounted in the position where the eyepieces would normally be located. There can also be additional magnification associated with printing or viewing but this does not really increase true resolution. At this magnification, the difference in the cellular appearance of squamous and cuboidal epithelial cells should be apparent in the lower portion of the image. Many of the cuboidal cells have distinct pink staining around their borders and the nucleus when present is generally oval shaped and positioned in the center of the cells. Three of these cells are present near the center of the image. For the low squamous cells surrounding the lumen of a smaller duct (lower portion of the slide), the cells have only a thin rim of cytoplasm, but the nuclei are prominent and seem to protrude into the lumen of the duct.

Figure 4.12 is taken with a 20× objective and is an image of a tangential section of a blood vessel, specifically a vein. You can see clusters of red blood cells in the lumenal space of the vessel. The cells that line the side of the lumen are endothelial cells. Notice the difference in the staining compared with Figure 4.10. This means you need to learn structures not based on color but on morphological characteristics.

Figure 4.13 shows a similar section through an artery at higher magnification. The box (yellow) in the figure indicates a portion of the tunica intima or interna, which is composed of simple squamous epithelial cells (also called endothelial cells), and the layer just under these cells, the tunica media, which has smooth muscle cells in arteries. The yellow arrow points to the nucleus of an endothelial cell and the red arrow to another endothelial cell nucleus, which was synthesizing DNA at the time, the sample was taken. The brown stain is due to the attachment of an antibody that is specific for the presence of bromodeoxyuridine (BrdU) an analogue of thymidine that is used to measure DNA synthesis. You should recall the relevance of these analogs in the study of cell proliferation from your earlier reading.

Before we leave our discussion on simple epithelium, as you have likely gathered from the figure descriptions, some simple squamous epithelia have specialized names. The term endothelium (meaning inner covering) is used to describe the lubricating, cell covering for all vessels of the cardiovascular system, including the lymphatic vessels and the internal surfaces of the chambers of the heart. Capillaries are specifically made of endothelium. This structure promotes rapid easy movement of nutrients to the surrounding cells as well as the corresponding uptake of waste products. Similar simple squamous cells also make up the mesothelium (middle covering) the epithelium that makes the serous membranes of the body. These are the coverings of the internal organs and body cavities that are well‐lubricated to allow organs to slide past one another.

Figure 4.14 is an image from a tissue sample taken from a section of the small intestine. A portion of a villus is shown with a layer of simple columnar epithelial cells covering the outer portion. The nuclei appear mostly in a row in the lower third of the cell. Notice the cells are tall and narrow.

Although not apparent at lower magnification, the apical ends of the cells have many microvilli, which add capacity for absorption. This is also called the brush border. If you look closely, you should notice that the outer rim of the cells looks as if they have been slightly colored. This is because the microvilli clump slightly and trap proteins when the tissue is preserved. These associated proteins and carbohydrates are called the glycocalyx. The accumulated material and closely aligned microvilli allow staining and explain the darker rim.

Can you distinguish individual epithelial cells? Columnar cells are usually associated with absorption and secretion and are found lining the intestinal tract from the stomach to the rectum. This epithelium has two modifications that greatly aid its functioning. The first is the presence of the microvilli that markedly increases absorptive surface and the second is the presence of goblet cells. These unicellular glands produce mucus that is secreted on the epithelial surface. This increases lubrication and provides protection. These specialized secretory cells also appear in the respiratory and reproductive tracts. Although the images shown in Figures 4.14 and 4.15 are excellent, representative examples of the features of intestinal tract epithelium, it is important to appreciate that not all histological sections are of such quality. Moreover, as indicated previously, the plane of section can make it difficult to interpret a given tissue section.

The image in Figure 4.16 is also a section through the intestine. It is still possible to distinguish the presence of villi and the appearance of the epithelium, but can you detect some of the problems? First, the image is a bit out of focus, and second, it is a bit too thick. This makes it difficult to distinguish individual cells. The villi have become pushed into one another during processing, so it takes some effort to distinguish individual structures. Finally, to the upper right and far right of the section, there are some tears that have altered the orientation of the tissue.

Many other artifacts also can occur. The point is that section preparation is sometimes as much an art as a science, so patience is needed as you study even professionally prepared slides. Regardless, several villi have been sectioned roughly along their longitudinal axis. This simply illustrates what you can and will see when you examine actual slides. Because you know what you are looking for in columnar epithelial cells from Figures 4.14 and 4.15, you should still be able to distinguish several villi covered by a layer of columnar epithelial cells.

Figure 4.17 illustrates a similar section of the duodenum, but the sample is from a calf and the animal was injected with BrdU 2 hours before the tissue was collected. Remember this is the analogue of DNA that gets incorporated into cells that are in the S‐phase of the cell cycle. In this section, many of the villi are cut at a tangent to the longitudinal axis but you can see that there are many brown stained nuclei (indicating the cells were synthesizing DNA, that is, the presence of BrdU) in the lower regions of the villi. It is well known that the cells that populate the villus proliferate in lower crypts and are lost from the upper region of the villus as they age. To maximize the opportunity to detect labeled cell nuclei but also be able to distinguish basic tissue structure the sample was only briefly counter‐stained in hematoxylin but without eosin. This gives the pale blue staining to the cells, but it is less distinct than in the H&E‐stained sections of intestinal tissue (Figs. 4.14 and 4.15).

Figures 4.18 and 4.19 give examples of simple columnar epithelial cells from the reproductive tract. The complex folding of the internal surface is evident (Fig. 4.18) and the regular arrangement of epithelial and goblet cells is apparent (Fig. 4.19).

Figure 4.18 shows a tissue section from the anterior (fornix) vagina of a cow taken during the follicular phase of the estrus cycle. Notice the epithelium is on the internal surface and as the higher magnification (40× objectives) image (Fig. 4.19) shows the epithelium is also a simple columnar epithelium.

Stratified Epithelium

To this point, we have considered examples of simple epithelium with squamous, cuboidal, or columnar cells. Now let’s consider stratified epithelium types. As you should surmise, the stratified types are better able to withstand physical trauma and wear and tear than simple epithelial but are much less efficient at absorption. This means these cells are also poorly adapted for secretion. When secretions are needed along a stratified epithelial surface this is usually accomplished by the presence of exocrine glands that are located inferior to the epithelial surface. Ducts that radiate from the glandular cells to the surfaces provide needed secretions. However, most of the lubrication for these internal epithelial surfaces is provided by goblet cells. As mucus accumulates in the cells, they eventually rupture to release their contents.

Remember that with stratified epithelium, the classification depends on the shape of the epithelial cells on the outer surface, adjacent to the lumen or free surface. The first image in this series (Fig. 4.20) is a section through the cornea taken at a very low magnification (4×) objective. The outside of the cornea is covered by a stratified squamous epithelium and the inside by a simple squamous epithelium. The bulk of the corneal structure (arrow) consists of collagen fibers arranged in lamella that are parallel to each other along with some scattered fibroblasts.

The outer stratified squamous epithelium of the cornea is about five cells thick (Fig. 4.21). The basal cells appear as cubes or polyhedrons, but the cells are progressively flattened as they migrate to the surface. Because the outermost cell layer is flatted, the classification is stratified squamous. Can you detect any of the fibroblast nuclei in the underlying substantia propria (the name given to the bulk of the corneal tissue)? Figure 4.22 shows the epithelial layer on the inner surface also at higher magnification. The cells are in a single layer, and they are highly flattened, so it is an example of simple squamous epithelium. Another area where this epithelial type appears is on the internal surface of the lung alveoli. What better way to promote rapid diffusion of gases than with a single layer of thin epithelial cells?

Figure 4.23 provides another very common example of stratified squamous epithelium. The section is from an internal body opening that is moist but requires protection. Examples of this type of epithelium would include the lip, mouth, posterior vagina, and anus. The bracketed area indicates the epithelial portion of the tissue; the lower portion of the image is the connective tissue or stroma. Notice the multiple layers of cells but the fact that the outermost layer of cells is flattened (arrows), therefore, the stratified squamous classification. In contrast to areas that are moist, the skin also needs the protection provided by multiple layers of cells, but the excess loss of moisture can be a problem for many animals. Figure 4.24 shows the beginnings of the keratinization process. The number of cell layers and classification is similar except that there is now a layer of keratin (a cellular protein) and a layer of progressively dying cells. This keratin layer provides protection. As a specific example, the keratin that is produced in the teat opening of lactating cows is a very important protection against mastitis. In experiments in which keratin has been artificially removed, the incidence of mastitis is markedly increased. Figure 4.25 shows a more extreme example of the protection that is provided by keratinization in the skin. Here dead and dying cells form a very distinct outer layer (between the brackets) that markedly increases protection against abrasion. The layer is especially increased in skin areas subjected to pressure. Figure 4.26 shows some of the cellular features of skin at higher magnification. Here you can begin to see staining and morphological characteristics that allow the epithelial cells in varying strata within the epithelium to be distinguished. These will be described in more detail in our discussion of the integumentary system.

Other types of stratified epithelium occur on the internal surfaces of some of the larger tubular structures in the body, that is, the trachea, reproductive tract, and bladder. These will be considered in subsequent slides. Stratified cuboidal epithelium is usually associated with various exocrine glands, in which secretions made by the secretory cells of the gland must be transported through ducts to be emptied. The cells, which compose the walls of the ducts, generally do not produce secretions themselves but provide a passageway for products to the site of secretion. Exceptions include the ductal cells of the salivary gland and pancreas, which can act to modify secretions produced by the acinar cells. Figure 4.27 illustrates a cross section through a duct leading from a sweat gland. Note the roughly double layer of epithelial cells. The tissue surrounding the duct is mostly collagen fibrils and other extracellular matrix materials, a few fibroblasts, and blood vessel cells.

The cells in Figure 4.28 illustrate a type of epithelium found in the trachea and areas of the reproductive tract. These are pseudostratified because although the cells appear to be residing in multiple layers, each of the epithelial cells is anchored to the basement membrane. This may only be by a thin projection of cytoplasm but because all the cells are attached the layer only appears to be stratified. The sample is from the oviduct of a cow. Clusters of cilia are evident as tufts protruding from the apical ends of the cells.

The drawing provided in Figure 4.29 illustrates the arrangement of pseudostratified epithelial cells. Again, the nuclei appear at various layers, but all are attached to the basement membrane. It is also usual for this epithelial type to have goblet cells and cilia. Another example of pseudostratified columnar epithelium is shown in Figure 4.30. This sample is a cross section through the epididymis of a bull. In this tissue, there is a more complex surface specialization, called stereocilia. These structures, similar but more elaborate than simple cilia, are evident as the elongated spikes that protrude into the lumenal space of the tubule. The center of the lumen is also filled with stored spermatozoa, a highly specialized epithelial cell.

The final epithelial type (Fig. 4.31) we will consider is transitional. This type appears in the lining of the bladder and it is unique because its appearance changes as the bladder expands and contracts. When relatively empty the epithelium is similar in appearance to non‐keratinized stratified squamous. As the bladder fills, the expansion reduces the number of apparent cell layers. In the non‐distended state, the rounded surfaces of the epithelial cells seem to protrude into the lumenal space. Notice the cross section of the vein and artery just below the epithelium. The nuclei of the larger circumference of the vein (upper) also provide an excellent example of simple squamous epithelium.

Epithelial Cell Junctions

Along the adjoining borders of epithelial cells, there are specialized cell junctions. These are regions or sites where some special contact between cells can be recognized. Three functional classes of junctional complexes include: (1) occluding junctions, (2) anchoring junctions, (3) and communicating junctions. Some of the communicating junctions, for example, the gap junction, also appear in other cell types. However, because of the importance of epithelial tissue in creating tissue compartments or barriers, it is important to understand the role of cell junctions in this process. To illustrate the idea of barriers, consider the differences between milk and blood. Blood circulates throughout the mammary gland within the capillaries just underneath the secretory epithelial cells of the mammary alveolus (see Fig. 4.8). However, the composition of blood or interstitial fluids and milk is very different. The same is true for the fluid environment of the gut lumen compared with the composition of the interstitial fluid of the lacteals in the villi of the intestine. How are these differences developed and maintained? This is where junctional complexes come into play.

In circumstances where it is necessary to maintain a seal between epithelial cells, the lateral margins of the cells become fused together along a system of membrane ridges between adjacent cells. These ridges extend completely around the perimeter of the cells to create a sort of belt located near the apical ends of the cells. These junctional complexes are called zona occludens or tight junctions to indicate that they produce an effective barrier. For example, during the latter stages of mammary development in the pregnant heifer, the approach of parturition signals both the structural differentiation of the alveolar cells and the maturation of tight junctions between the cells. Increases in circulating glucocorticoids, along with declining progesterone, seem to be especially important. Once this occurs, paracellular (transport of components between the cells) is dramatically reduced. This creates an effective blood–milk barrier so that transfer of serum components into milk or milk constituents into blood is minimized. This does not mean that transport cannot occur but that wholesale leakage is prevented. The effectiveness of this barrier function is readily apparent from a study of secretions obtained from animals with acute mastitis or experimental treatments known to disrupt the tight junctions. One of the effects of this disruption is the appearance of serum proteins in milk, for example, albumin. Conversely, these situations also allow abrupt increases in the appearance of lactose and α‐lactalbumin (and likely other milk components) in serum.

Adhering junctions are a second class of membrane specializations that act to anchor epithelial cells together. These complexes also appear as bands or belts that circumnavigate the perimeter of the cells below the level of the tight junctions. In intestinal epithelial cells, these complexes are called zona adherens. As you traverse along the lateral membrane toward the basal end of the cell, a second type of adhering junction, the desmosome or macula adherens appears. Anchoring junctions are widely distributed and allow the epithelium to maintain structural integrity by linking cells together and linking cells to the underlying extracellular matrix. These complexes are plentiful in tissues that are subjected to mechanical stress, for example, skin. The adherens junctions are focal points where actin filaments attach to the junctional proteins. In general terms, there are two basic parts of these complexes. The intracellular attachment proteins create a plaque or thickening on the cytoplasmic side of the cell membrane and provide sites for the attachment of cytoskeleton proteins and transmembrane linker proteins. The transmembrane linker proteins have cytoplasmic tails that attach to the plaque, but the extracellular domains of the proteins interact with the extracellular domains of adjacent junction proteins or with other extracellular matrix proteins, that is, hemidesmosomes. In the case of the adhesion belts in epithelial sheets, the complexes in companion cells are directly opposed. The transmembrane linker protein is a member of a family of Ca²⁺‐dependent proteins called cadherins. The plaque or adhesion belt through the actions of several linker proteins (catenin, vinculin, and others) binds bundles of actin fibers that radiate into the cytoplasm interacting with the cytoskeleton. It is thought that changes in the orientation and contraction of these bundles explain the folding of epithelial sheets to create tubular structures during development.

Desmosomes, unlike the bands of the zona adherens, are limited to spots or patches of the membrane between adjacent cells. They could be envisioned as spot welds or small dollops of glue to help bind adjacent epithelial cells together. To carry this analogy a bit further, the zona adherens could be thought of as miniature packing straps that bind the epithelial cells. Both the zona adherens and desmosomes are closely associated with microfilaments within the cytoskeleton of two cells that are linked. A variant of the desmosome the hemidesmosome has the structure of only half a desmosome. This complex serves to anchor the epithelial cells to the underlying basement membrane. For desmosomes, the transmembrane linker proteins also belong to the cadherin family of proteins, but the specific intracellular protein associated with the plaque varies. In most cells, these are keratin filaments but desmin filaments fulfill the same function in cardiac cells.

A final type of structure is the gap junction. In this instance, proteins aligned in neighboring cells essentially create pores that pass from one cell to the other. This can be imagined as small pipes passing between two adjacent apartments. Gap junctions appear not just in epithelial tissue but are prominent in cardiac muscle, some types of smooth muscle cells, and between cells of the nervous system. Gap junctions allow for the direct passage of small molecules (typically less than 300 MW) between cells. This is important for cell‐to‐cell communication and rapid responses necessary for nerve function and muscle contraction. We will discuss the specific physiological events related to cell junctions in subsequent chapters. A stylized view of cellular junctions is provided in Figure 4.32. Figure 4.33 illustrates the structure of the gap junction.

Gap junctions are composed of transmembrane proteins called connexins. When arranged to create a complex, six connexin proteins align to form a pore or channel called a connexon. As illustrated in the upper panel, when connexons of two adjacent cells become aligned, they create an aqueous pore that connects the two cells. However, unlike tight junctions, the outer leaflets of the adjacent cells are not fused. Gap junctions can also alternate between open and closed states. For example, a decrease in pH or an increase in Ca²⁺ concentration promotes closure. Consequently, the functionality of gap junctions can be regulated.

Glandular Epithelial Types

Numerous glands serve multiple physiological functions. The simplest classification of glands is based on the number of cells. The single or unicellular gland represented by mucus‐secreting goblet cells is the most rudimentary. Multicellular glands include two subtypes: (1) exocrine and (2) endocrine glands. Exocrine glands are familiar examples, that is, salivary or mammary glands, in which products or secretions made by the epithelial cells are transported via a duct to be emptied. Endocrine glands, in contrast, are ductless. Hormones produced from these secretory cells are captured by capillaries surrounding the tissue and transported to target tissues throughout the body. We will consider the structure and function of endocrine glands in subsequent chapters.

In addition to the structural organization of multicellular exocrine glands, there are also differences in how secretions are released from the cells. Early anatomists tried to define the origin of the mammary gland by classifying the secretion mechanism for the secretory cells. To illustrate, sebaceous glands exhibit a holocrine mode of secretion in which cells are ruptured and sloughed to become a part of the secretion. Sweat glands follow an apocrine mode of secretion in which only portions of the cells are lost so that individual cells are capable of periodic secretion. Other glands follow a merocrine mode of secretion in which products are secreted, but the secretory cells remain intact. Mammary cells follow both apocrine and merocrine modes of secretion. Specifically, as lipid droplets form in the cytoplasm of the cells, these droplets progressively enlarge, migrate to the apical end of the cell, and protrude into the alveolar lumen until the membrane‐bound droplets pinch off to become the butterfat of milk. Because the membrane surrounding the lipid droplet is derived from the plasma membrane of the cell, a portion of the cell is lost to become a part of the cellular secretion. This is an example of an apocrine mode of secretion. For secretion of specific milk proteins and lactose, these products are packaged into secretory vesicles in the Golgi apparatus. These vesicles both singly or in chains fuse with the apical plasma membrane and release their contents via exocytosis. Because only the secretory vesicle contents are lost from the cell, this mode of secretion is merocrine. The details for secretion patterns of mammary cells were not settled until mammary tissue from lactating mammals was studied with transmission electron microscopy in the early 1960s. Thus, attempts to determine the phylogeny of the mammary glands based solely on secretion patterns were futile. It seems likely that the primitive mammary gland arose from a hybrid combination of both types of glandular cells. Diagrams showing holocrine, merocrine, and apocrine modes of secretion are shown in Figure 4.34.

Epithelial glands follow several distinct patterns of development based on the arrangement of cells within the secreting unit of the gland. Simple glands have a duct that opens onto a surface. Usually, cells that create the duct opening or neck are nonsecretory and serve as a passageway for products made deeper within the gland. The shape of the gland mimics the shape of tubes or rounded flasks called alveoli or acini. The presence of a single glandular unit denotes a simple gland. Depending on the shape of the secretory structure, the gland is classified as simple tubular or simple alveolar. By contrast, compound glands are branched with multiple secretory units opening into a duct. Depending on the specifics of the secretory units, glands are classified as compound tubular, alveolar, or tubuloalveolar. Mammary glands are compound alveolar glands. Various arrangements of the cells within glands are illustrated in Figure 4.35.

The type of products they secrete also distinguishes subclasses of exocrine glands. Mucus glands produce a viscous glycoprotein mixture called mucus. Serous glands produce a watery or whey‐like secretion that contains enzymes. The exocrine portion of the pancreas is an example. Some glands (e.g., parotid salivary glands) produce both types of secretions because they contain a mixture of mucus and serous cells. In typical H&E‐stained sections, mucous secretory units are very pale stained compared with the serous secretory units. The serous cells usually have an intense basophilic staining of the basal areas of the cells. This is because of the abundant amounts of endoplasmic reticulum, as the cells are actively producing proteins for secretion. The pale‐staining mucus‐secreting cells typically have a flattened nucleus with most of the area of the cells packed with vacuoles containing mucus. Examples are illustrated in Figure 4.36 (Box 4.2).