GLANDS
Objectives
The objective for today is to become familiar with the general appearance of exocrine glands and their classification scheme based on structure.
| You should become able to: |
1. distinguish secretory and duct portions of glands in sections of tissues.
2. understand the nomenclature for describing the secretory and duct portions of glands.
| intralobular | myoepithelial cell | |
| interlobular | exocrine | |
| simple | eccrine (merocrine) | |
| branched | apocrine | |
| compound | holocrine | |
| tubular | serous | |
| acinar (alveolar) | mucous | |
| excretory duct |
3. distinguish serous from mucous cells after H&E and PAS staining.
4. classify glands in sections of tissue as simple, branched or compound.
* * * * *
 |
Blue Histology |
Slides
|
|
|
D-63 | Mammary gland |
|
| | D-64 |
Lactating breast |
 | D-114 | Colon | |
|
| | D-122 |
Pancreas |
|
| | D-128 |
Submaxillary (submandibular) gland |
| D-162 | Sebaceous gland (scalp) | |
| D-165 | Fingertip (H&E) | |
| D-170 | Lacrimal gland |
Optional slide
| D-127 | Submaxillary gland (PAS stain) |
Prologue
The word "gland" implies a specialized secretory function, which in turn implies cell specialization. Therefore we classify glands only by their general arrangement, and whether they are exocrine or endocrine. Exocrine glands represent invaginations of ectodermal or endodermal epithelia and in general, the larger the gland is the deeper it penetrates into the underlying connective tissue. The simplest sort of gland amounts to little more than a localized pocket of goblet cells within an epithelium. (Some people even call a single goblet cell a "unicellular gland".) Larger glands extend into the lamina propria, or penetrate through the mucosa into the submucosa if still larger. Some very large glands protrude all of the way through the wall of an organ and form a separate organ on its own, e.g. liver, pancreas, salivary glands.
Small glands may be composed entirely of secretory cells. These may be arranged in a blind tube leading to the surface. The pattern of invagination decides whether they are branched or unbranched, and whether they are straight or coiled. More substantial glands typically are differentiated into a duct portion connected to the surface and a secretory portion at the distal end. If the gland is a large one the ducts branch as they descend, to form a compound gland instead of a simple gland.
Ducts with only a conductive function are called excretory ducts. Smaller twigs of duct in some glands have auxiliary secretory functions, such as adding, removing or substituting particular ions to the secretion. Another sort of duct function is to store secretions that are released only periodically. In this case the ducts are expanded. The functions of the ducts vary from one gland to another and ducts may be given names specific to a particular gland.
Histologists also name ducts by a second, alternative scheme; according to their position. Ducts that lie within a lobule are called intralobular and typically are nestled in amongst the secretory units. The analogy with a bunch of grapes is useful, with the stem connecting the grapes (standing for the secretory units) being intralobular ducts. The entire lobule empties through a single final interlobular duct. This duct emerges from the bunch of grapes - no, I mean from the lobule - and runs in the connective tissue between lobules. There will joins with the ducts from other lobules to form a branching system of interlobular ducts. Thus we have two parallel systems of nomenclature, 1) according to structure/function and 2) according to location. For example, interlobular ducts usually are excretory. Also, the submaxillary salivary gland described below has three types of intralobular ducts, "intercalated ducts", "striated ducts" and short segments of "intralobular excretory ducts".
The shape of the secretory units also is taken into account in the classification of glands. In the above analogy to a bunch of grapes, the rounded clusters of secretory cells are called acini (singular: acinus) or alveoli. Elongated secretory units are described as tubular. Tubuloalveolar glands have an enlarged swelling at the ends of the tubules. All of these adjectives are run together in classifying glands. Thus, as we will see below, the submandibular gland is a branched compound tubuloalveolar gland.
Endocrine glands also originate as outpocketings of endodermal or ectodermal sheets, and so originally have a rudimentary duct system. This degenerates as the gland matures, isolating the cluster of endocrine cells deep within the body. We will defer consideration of this type of glands for a future laboratory session.
* * * * *
Slide descriptions
D-114 Colon (H&E)
The colon has two grades of glands. The simpler are individual goblet cells scattered in the surface epithelium as "single cell" intraepithelial glands.
More substantial are the simple tubular glands which extend down the full thickness of the lamina propria of the mucosa. They empty individually onto the surface directly without intervening ducts. These glands have several acceptable names; "mucosal glands", based on their location, and "crypts of Lieberkühn" as a specific proper name for the mucosal glands of the large and small intestines. They also can simply be called the "glands of the colon" because they are the only glands of that organ (ignoring individual goblet cells).
The glands of the colon have two fundamental functions. First they are secretory. Their abundant goblet cells produce mucus. You will have no problem identifying their large pale mucous cells. The glands also are cytogenic. The stem cells for the epithelium that lines the intestines are located down in the glands. Here they divide continually (with a generation time of about one day). The newly formed cells get pushed up the glands and onto the surface. Within a few days they die, are sloughed and are replaced. Presumably the stem cells are sequestered in the glands to protect them from the rather hostile environment of the lumen of the GI tract.
The epithelium of the glands is simple columnar. The nuclei are close to the base of the cells and the apical region, in the case of the goblet cells, is filled with secretory material. The "free surface" of the epithelium is a small tubular lumen which extends to the surface. A basal lamina, which you cannot see, surrounds each gland and separates its epithelial cells from the surrounding connective tissue.
An elongated structure, such as a gland will appear quite differently when cut in different orientations (illustrations of three orientations). As discussed in earlier laboratory sessions, it is always important for you to find areas with the simplest plane of section for your study. In this case you should look for a region which has been sectioned perpendicular to the surface, so that the tubular glands are shown longitudinally. Then find a section cut parallel to the surface, where the glands are cut transversely. In most unselected sites the glands will be cut obliquely to some degree or other.
The longitudinal view will show you: 1. The length of the glands. They extend the full thickness of the lamina propria. 2. That the glands are straight instead of coiled. 3. That the glands have no ducts. Find an example of a gland opening onto the surface.
The transverse section lets you see that the glands: 1. Are round in cross section. 2. Have a small lumen. 3. Are surrounded by a loose, cellular connective tissue. 4. Are abundant. Estimate the percentage of the volume of the lamina propria taken up by the glands versus the surrounding connective tissue.
D-165 Fingertip
(H&E)
[If the tissue on your slide does
not resemble the picture above, obtain a replacement slide]
Sweat glands are a good example of the next stage in glandular complexity. They are coiled simple tubular glands but with a differentiated secretory and duct portion.
In the fingertip, the ducts extend from the epidermis
(stratified epithelium, dark pink) deep into the connective tissue dermis (light
pink) illustration. At the
base of the dermis they start coiling, and then change abruptly to secretory portions.
Because the secretory portion and part of the duct is highly coiled, you can easily
find clusters of randomly oriented sections of both (illustration).
It is worthwhile looking at sections cut at various angles. The ducts are
derivatives of the epidermis and retain their stratified character by consisting
of a double layer of basophilic cells, best observed in transverse sections. The
secretory cells are larger and paler than the duct cells, and form a single pseudostratified
layer. Some nuclei are dark while others are paler and the two sorts of nuclei
lie at different heights. Since all of the cells touch the basement membrane the
epithelium is pseudostratified.
| List four ways that ducts differ visually from the secretory portions of sweat glands | ||
| 1. | ____________________________ | |
| 2. | ____________________________ | |
| 3. | ____________________________ | |
| 4. | ____________________________ | |
You will be able to find myoepithelial cells at the periphery of the secretory portions of the sweat glands if you look carefully. These are bona fide epithelial cells within the basement membrane but they have long arms of cytoplasm filled with actin and myosin. Therefore, they can contract and squeeze the sweat out of the lumen of the gland. Because of the high content of these contractile proteins the cytoplasm of myoepithelial cells is substantially more eosinophilic than that of the secretory cells. Looking at the picture above would you say that the arms of cytoplasm tend to extend longitudinally along the glands or that they tend to wrap circumferentially around the glands? Right! and this is what they look like if a section is cut tangentially through the very edge of a gland.
D-170, Lacrimal gland
The lacrimal gland produces the tears to keep the eye moist. It is a tubular gland but one that is branched and compound. This allows the gland to be much larger than the individual glands of the colon or fingertip. Because of its size the lacrimal large gland is divided into a series of lobules by septa of connective tissue. This connective tissue provides pathways for blood vessels, nerves and large excretory ducts. It is clear that lobules are units of structure. You have no trouble picking them out visually. They are also units of function. All of the secretion produced by a lobule is carried away in one interlobular duct. This overlap between the structure and function of lobules of glands is the usual case but not universal. In the liver, the unit of structure as indicated by the stroma does not correspond to the lobule as a unit of secretory function. This leads to ambiguity (as we shall discuss in the liver lecture). However, the few exceptions merely underscore the strong usual correspondence between subunits of structure and of function among most glands (and other organs).
You will have little problem picking out large interlobular ducts in the connective tissue partitions between lobules. They are lined by a low stratified, pseudostratified or simple columnar epithelium, depending on their size. They are simply transport pipes to the outside and therefore called excretory ducts. These ducts originate within individual lobules and fuse into a single duct which travels to the under the eyelid. Developmentally, a column of epithelial cells from the conjunctiva (the mucosa of the inner eye lid) grew all of the way down through the lamina propria and then branch in the underlying C.T. to form an independent organ deep behind the eyelid. The last parts of the gland to form were the secretory units.
The excretory ducts extend a ways into the lobules and branch there a few times before changing to the secretory portion (see diagram in the printed syllabus). However, for the most part the tears run through the tree of branching secretory tubules in the gland. Because fluid collects from long coalescing tubules the lumen becomes fairly large as it approaches the excretory duct. Therefore some of the sections through the tubules show a much larger lumen than that of the sweat gland that you just looked at. Other sections cut near the ends of the tubules have small lumens. This variation in cross sections is just what one would expect for a branched tubular gland (am I right or am I right?) If you snoop around you can find some sections that are cut longitudinally for a ways. They show clearly that this gland is tubular instead of acinar.
Look at the secretory cells. They are tall cuboidal and stain palely. Their main action is to secrete fluid. They do this by pumping ions across their apical membrane and allowing water to follow passively. For this they need energy and so have a substantial component of mitochondria. Mitochondria stain well with eosin and you will find that cells with an abundance of them characteristically are strongly acidophilic. Tears also contain a small amount of protein, especially lysozyme. The secretory cells synthesize this protein and therefore they should have a slight basophilia. Can you verify this? Compare their color with the low, cuboidal epithelial cells of the excretory duct which do not synthesize proteins.
One last note: Any gland divided into lobules must be compound. If the duct from each lobule emptied separately to the surface instead of fusing into a single final duct, the tissue would be considered to be a collection of glands instead of one gland (Indeed, this is the case for the prostate and breast. A breast has mammary glands in it.). Finish this slide by taking a last look at the delicate sheets of connective tissue ramifying throughout the lobule to invest each tubule. Where would the basement membranes in this gland be?
D-122 Pancreas (H&E)
The pancreas is another gland large enough to need septa of connective tissue to break it up into lobules. It demonstrates several further glandular features of interest. First, it is actually two glands in one. Most of the tissue is a compound exocrine gland, with secretory units and ducts. However, it also includes clusters of endocrine cells. These are the islets of Langerhans that produce insulin, among other things. Their destruction leads to diabetes, as you undoubtedly know. You can find these islets as round balls of paler staining cells plunked down within the lobules of exocrine tissue. We will deal with their cells later, but you can easily see (using 430X) that they are arranged very differently from exocrine glands. The cells are bunched into irregular sheets or clumps with no lumen or ducts. Most of the natural spaces between the cells are enlarged capillaries and it is into them that the cells secrete.
Direct your attention to the exocrine pancreas. The secretory units are acini instead of tubules. That is, they are more or less round (actually spherical - my flat-earth friends do not dispute that the world is round) and larger than the duct that they drain into. The acini are composed of several dozen cells and show usually 3-5 nuclei in a section. Pick out these units, which may be easiest to recognize at the edge of the lobule. Each acinus has a lumen in its center but this usually is very difficult to see. It is only large enough to handle the secretion from a few dozen cells. The lumen drains into a small duct called an intercalated duct, example2. These ducts fuse with one another and finally run into an excretory duct (again, see the diagram in your printed syllabus). Intercalated ducts are abundant but somewhat hard to recognize. Do not waste much time searching for them on your slides at this time. Remember, we will return to a relatively leisurely lab on the pancreas and liver when we consider the digestive system.
Although intercalated ducts are hard to find the excretory ducts are obvious. They usually are surrounded by a layer of eosinophilic connective tissue. The excretory duct system begins within the lobule and continues in the connective tissue between lobules. The final duct from the pancreas leads into the duodenum. This is where the exocrine tissue originated: the endocrine portion migrated in from the neurocrest.
Examine the acinar cells at high power. Their main function is to synthesize and secrete digestive enzymes for the small intestine. True, they have to secrete some water as well (the trypsinogen, chymotrypsinogen, nucleases etc. obviously do not sift through the ducts as a powder) but their main product is proteinaceous. Actually, it is the duct cells that secrete most of the water. They also pump bicarbonate ions into it to raise the pH for the intestine, but that is another story for later. The structure of the acinar cells strongly reflects their synthetic function. The cells are dark staining and basophilic. Most of the numerous ribosomes are located in the basal part of the cells. The apical regions are filled with secretory granules. These contain the digestive proenzymes. Where the preservation is good the granules are visible as eosinophilic dots in the tops of the cells. If the contents of the granules have leeched out, the apical the cytoplasm will look "foamy". Contrast the appearance of these cells with those of the lacrimal gland that synthesize only traces of protein.
Before leaving the pancreas, let’s review its features of interest.
| 1. | a combination of endocrine and exocrine tissues. Why do you think that they are intermingled in a single organ? | |
| 2. | two types of intralobular ducts. What are they called and what is the function of each? | |
| 3. | acinar organization: Can you recognize a compound acinar gland from a compound tubular gland? Yes? Good for you! | |
| 4. | protein synthesis. Could you now make a good guess as to whether or not an unknown gland that you come across produces a secretion rich in protein? | |
| 5. | What else can you learn from this slide?? If your mind is blank, how about this minor point. The acinar cells of the pancreas have to be wedge shaped to fit into a spherical acinus. They are usually described as pyramidal instead of cuboidal. If you wish to call them and the epithelium cuboidal, that is OK. Their nuclei are round. But be prepared to nod wisely if some instructor or board exam question mentions the "pyramidal" acinar cells of the pancreas. Wait a minute; what does the shape of the nucleus have to do with this? |
D-128, Submaxillary (submandibular) gland (H&E)
Scan this slide with your 3.5X objective, noting that the gland is divided into lobules by connective tissue. At higher power observe that there are two types of secretory cells: mucous and serous (illustration). The mucous cells stain poorly and have darkly stained nuclei flattened out at the base of the cell. (Mucus is a noun, mucous the adjective, thus, mucous cells produce mucus). These cells are closely related to goblet cell. The serous cells are stained vigorously by hematoxylin. The basophilia suggests quantities of ribosomes; indeed, this cell type makes enzymes for export. Its secretion is watery instead of gooey, even though it contains a high concentration of dissolved protein.
Note that the two types of cells stick with their own kind pretty much instead of intermingling (like the men and women [blokes and birds] at an Australian cocktail party.) The mucous cells would correspond to the Australian males who hog the center positions around the doorways. The serous cells are exiled to the periphery, either as all-serous acini or as a layer of cells that cap the distal end of a mucous acinus. (I love going to Australian parties because the blokes are always out of the way.) The serous caps look crescent shaped in the right plane of section and therefore are called serous demilunes (demi, hemi, semi, half - they all mean the same, and lune refers to the moon, as in Sydney's Luna Park - the Coney Island down under.)
The distinction between serous and mucus cells is very important, so make sure that you can see their differences on this slide. Some glands are wholly serous or mucous, while many others, as seen here, are mixed serous-mucous.
Ducts are easy to distinguish in this tissue. The interlobular ducts are excretory. They are lined with simple, pseudostratified or even stratified epithelium depending on their size. The ducts within the lobules (intralobular) are more complex. They consist of two types; intercalated and secretory. Check the diagrams in your textbook. Intercalated ducts are similar in appearance to those of the pancreas, which you have just looked at. They are formed of elongated, tall squamous, epithelial cells with elongated nuclei and are not easy to find. Intercalated ducts run into striated ducts (example). Secretory = striated ducts are more substantial. They shift ions into and out of the secretion flowing through them. These activities require energy and therefore the ducts have an abundance of mitochondria. Because mitochondria have large amounts of insoluble protein, cells with a lot of them stain bright red with H&E. Here the elongated mitochondria are arranged vertically at the base of the cells. If the ducts are especially well preserved the mitochondria appear as fine radial striations at the rim of the duct. For this reason "striated duct" is a synonym for these secretory ducts. Unfortunately, our material is not preserved well enough to show these striations distinctly, although you may be able to imagine them in some sections..
Lastly, the submaxillary gland is tubulo-alveolar in form. This is why the secretory units look so messy. Most of the all-serous secretory units are spherical acini but many of the mucous units are (branching) tubular with swollen acini at the ends. Can you more or less make this out in the picture to the right or in your slide - it is not easy? Actually, most compound glands are tubuloalveolar. Even the lacrimal gland, which I described earlier as tubular is usually considered to be tubuloalveolar. If it is tubuloalveolar, it is just barely so. If I lied to you I just barely lied.
D-63, Mammary gland (H&E)
This slide is from a female who had never given birth and probably was a child. At this stage of development the gland consists almost entirely of ducts. True secretory units do not form until pregnancy. Nevertheless, the lobular organization is easy to see by eye and at low power. The ducts are embedded in intralobular connective tissue that is quite cellular. The lobules are surrounded by less cellular interlobular connective tissue. It contains numerous adipose cells. The prepubertal breast tissue does not differ markedly from the postpubertal, nulliparous breast with regard to its glandular tissue. The duct system is somewhat more rudimentary in the child but mainly the breast is is much, much less filled out with fat.
Slide D-64, Lactating breast
Compare the glandular tissue in this section with that in slide D-63. Note that the lobules are greatly expanded due to the addition of more ducts and secretory alveoli (illustration). The interlobular septa are stretched thinner than in the resting breast.
It is difficult to tell the intralobular ducts from the alveoli because both are lined with secretory cells that secrete milk (illustration). Do not worry about distinguishing them. The ducts need larger lumens because they also store the milk between breast feedings. Observe the jagged lumenal surfaces of the secretory cells. These cells secrete in an apocrine manner, by pinching off vesicles of their apical cytoplasm containing fat droplets. The material inside the expanded ducts is milk. The alveoli and ducts are provided with many myoepithelial cells. Their nuclei are elongated instead of spherical. Another abundant cell type is the plasma cell. These cells make antibodies that are secreted into the milk. (We will discuss the structure and function of plasma cells later when considering the lymphatic system, so do not worry too much about these cells now.)
I probably don't have to point out that the preservation of this tissue is not the best.
D-162 Scalp (H&E)
Use this slide to look at sebaceous glands. They can be located as clusters of very pale-staining foamy-looking cells in the dermis associated with the hair follicles. In fact these glands empty their secretion into the crevice between the hair and the outer root sheath surrounding it. They are simple branched acinar glands with a stratified epithelium. Their cells undergo holocrine secretion; that is, the entire contents of the cell are shed as the oily exudate called sebum. A single layer of flattened basal cells along the basement membrane at the outer edge of the gland can divide. As the resulting cells get pushed into the interior, they fill with lipid droplets. This gives them a spongy appearance. Eventually, the cells cannibalize their intracellular organelles and lyse. The lysed cells are pushed as a goo into the short duct leading into the hair follicle. Try to find a gland sectioned to show the full height of the epithelium so that you can trace the stages that the individual cells go through as they mature (example).
If you were unhappy with the preservation of sweat glands on slide D-165 you get another chance to examine these structures here. Use the diagram above to find where they are located, about half way down in the dermis.
* * * * *
Optional slide
D-127, Submaxillary gland (PAS stain)
This slide has been stained for carbohydrates to emphasize the mucous cells. Now these cells have their turn at staining darkly and the serous cells are pale (why is this?) What percent of the secretory cells would you say produce mucus? Can you see pale serous "demilune" cells capping a red mucous alveolus on your slides? Well, can you at least distinguish the intralobular ducts from the serous acinar cells?