Glands are composed of secretory epithelial cells (glandular cells), which are specialized in the synthesis, storage (not in all cases), and secretion of various products. These products can vary greatly in nature (peptides, proteins, carbohydrates, lipids, amines).
The synthesis, storage, and release of each of these types of products require the development of specific cellular organelles, such as ribosomes, rough endoplasmic reticulum or smooth endoplasmic reticulum, Golgi apparatus dictyosomes, etc., forms of storage, if applicable, for example, in granules, and for their secretion. Thus, different types of glandular cells exhibit specific characteristics that allow histological recognition.
Glandular cells generally display cellular structural and functional polarity, which is due to the presence of a secretory pole, through which the secretion product is released, and a synthesis pole for the same, where cellular organelles involved in its formation are located. When the secretion product is stored in granules, they accumulate at the secretory pole.
In addition to the type of secretion product, glands are histologically classified based on the medium to which they discharge their secretion and their structure, including the number of cells that form it, the shape of secretory accumulations, and other characteristics, as described below.
- Exocrine glands secrete their products into the external environment, including the body surface or the lumen of hollow organs that are in contact with the external environment (digestive tract, respiratory pathways, urinary and genital ducts).
Exocrine glands maintain continuity with the lining epithelium from which they originate, so that their secretory pole communicates with the external environment, either directly or, more commonly, through an excretory duct formed by a continuation of the lining epithelium itself.
- Endocrine glands lack excretory ducts, and their secretion products, known as hormones, are released into the internal environment (blood, hemolymph, interstitial fluid, etc.).
- Unicellular glands are composed of individual secretory epithelial cells, such as goblet cells located among the lining cells of the intestinal epithelium in vertebrates.
- Multicellular glands consist of clusters of secretory cells, often along with lining epithelial cells, typically accumulating in specific anatomical regions to form organs. Examples include the macroscopic salivary glands in mammals. In other cases, glandular cells are embedded within other organs, such as the Langerhans islets in the pancreas of mammals, containing endocrine cells.
These are glands that secrete their products into the external environment, either onto the body surface (epidermis, gills) or into the lumen of hollow organs with openings that connect to the outside (digestive and genitourinary tracts, respiratory pathways, lungs). They can be both unicellular and multicellular. They secrete a wide variety of products of different natures, primarily glycoproteins, mucopolysaccharides (mucus), lipids, waxes, and also ions.
Unicellular exocrine glands are located among the cells of lining epithelia, with their apical pole facing the external environment. The secretory pole of these glands is oriented towards the apical pole of the epithelium, while the nucleus and synthesis organelles are situated towards the cellular basal pole and the epithelium.
In multicellular exocrine glands, secretory cells accumulate in specific regions, forming adenomeres, which contain a lumen continuous with the external environment, toward which the secretory pole of the glandular cells is oriented.
The adenomeres can either directly connect with the lining epithelium they originated from, i.e., open onto the surface of the epithelium, or they can be situated deeper within the connective tissue (lamina propia, dermis) and connect to the superficial epithelium through an excretory duct. This duct is formed by lining epithelium, which, depending on the gland, may exhibit characteristic specializations, such as basal striations in some mammalian salivary glands.
The basal limit of each adenomer is marked by the presence of the basement membrane, which is continuous with that of the excretory duct epithelium and the lining epithelium it communicates with.
In some multicellular glands, myoepithelial cells, branched and contractile, are located beneath the glandular epithelium or the excretory ducts, enveloped by the basement membrane of the adenomer or duct.
Both adenomeres and excretory ducts are supported by underlying connective tissue. Generally, the connective tissue closest to adenomeres is loose in nature and contains reticular fibers, which surround the adenomeres.
Larger multicellular glands are typically encapsulated by connective tissue and divided into portions. The larger divisions are referred to as lobes, and their subdivisions are known as lobules. These divisions arise from connective tissue septa that extend from the capsule and branch out to form increasingly finer septa. Vascularization and innervation run through these septa to supply adenomeres and, if present, excretory ducts.
Based on their shape, unicellular glands are referred to as cuboidal or columnar. A particular case of columnar glands is the goblet cells, which are mucous cells found in the intestinal epithelium. These cells have a goblet-like shape, with a tapered basal end, a basal enlarged part housing the nucleus, and a secretory apical end with a globular shape.
Pluricellular glands are classified based on the morphology of adenomeres and the presence or absence of excretory ducts, as well as whether these ducts are branched or not.
Regarding excretory ducts, they can be distinguished as follows:
-Secretory Lining Epithelia, both stratified and simple, lack excretory ducts and consist mainly of mucous-secreting cells.
In the case of simple epithelia, the mucus forms a continuous layer of certain thickness on the epithelium, and mucous granules are not observed at the apical pole of the cells. These epithelia are also referred to as simple epithelia with a closed mucous apical border.
- Simple Glands, where the adenomer or multiple adenomeres open to the exterior through a single excretory duct. When multiple adenomeres open into the same excretory duct, the gland is branched (branched simple gland).
- Compound Glands, which have multiple adenomeres with individual excretory ducts that unite to form a branching pattern of branched excretory ducts. The excretory ducts of compound glands have different names based on their location, generally ranging from initial (smaller) ones to the final ducts that open to the exterior, intralobular, interlobular, and interlobar
Based on their shape, adenomeres are classified as:
- Acinar or alveolar, with rounded or enlarged sac-like adenomeres and wide lumina.
- Tubular, when the adenomer has an elongated shape, which can sometimes coil upon itself to form a spiral, and its lumen is narrow.
- Tubuloacinar, when the proximal portion near the excretory duct of the adenomer is tubular, and the distal portion (the bottom) is acinar.
Based on the type of secretion product, both unicellular and multicellular exocrine glands are classified into:
- Mucous glands, which secrete mucopolysaccharides, resulting in a viscous secretion (mucus). In most mucous glands, these cellular types present an apical cytoplasm filled with mucus granules, which do not stain with routine techniques like HE or trichrome stains, thus appearing empty. The mucus contained in these granules can be visualized using staining techniques for mucopolysaccharides, such as the PAS or the Alcian Blue stain. This latter technique, based on the pH of the dye, allows differentiation between neutral, weakly sulfated mucopolysaccharides, which stain greenish, and strongly sulfated, deeply blue-staining basic types.
In both unicellular glands and mucous adenomeres of multicellular mucous glands, the nucleus and organelles involved in mucopolysaccharide synthesis are located in the basal part of the cells. However, this is due to the fact that during tissue fixation and embedding processing, mucus granules swell, causing the displacement of the nucleus and organelles towards the basal pole. Thus, in developing mucous cells, the nucleus occupies a more central position.
- Serous glands, whose secretion consists of proteins or glycoproteins, which accumulate in granules of various sizes and staining characteristics, either acidophilic or basophilic, or form complex structures, depending on the nature of the protein(s) they contain.
The cytoplasm of serous exocrine cells presents basophilic perinuclear regions, corresponding to accumulations of rough endoplasmic reticulum, and the nucleus tends to be located centrally or slightly displaced toward the basal pole. In proximity to the nucleus and to the cisternae of the rough endoplasmic reticulum, Golgi dictyosomes are located, from which the secretory granules are formed.
- Mixed glands, a term applied to multicellular glands that contain both mucous and serous adenomeres, which can be located in different lobes or lobules or mixed within the same gland.
Similarly, this class includes mixed adenomeres, which are characteristic of submandibular salivary glands in mammals. In these adenomeres, mucous cells accumulate toward the proximal end of the excretory duct, while serous cells are usually located in the distal part, forming the so-called von Ebner's serous demilunes (or Gianuzzi's demilunes).
Mixed secretion is also found in the fundic glands of the stomach in vertebrates, which contain mucous cells (neck cells) and serous cells (chief cells). Moreover, in mammals, these glands contain oxyntic cells (or parietal cells) that secrete Cl- and H- ions (hydrochloric acid).
Furthermore, mammary adenomeres are also mixed, with secretory cells that produce serous secretion (milk proteins), lipids, and carbohydrates (lactose).
- Sebaceous glands, which synthesize and secrete fatty substances in the form of droplets within their cytoplasm. In histological techniques using paraffin embedding, the lipids are removed by organic solvents, and the cytoplasm shows only the voids left by the lipid droplets.
Based on the manner in which the secretory product is released, exocrine glands are classified as follows:
- Merocrine glands release their secretion through exocytosis. In other words, the product is stored in granules, and the membrane of these granules fuses with the plasma membrane, allowing the secretion to be released. This is the case for mucous secretion by goblet cells and serous secretion by exocrine pancreatic cells.
- Apocrine glands release their secretion by shedding a portion of the apical pole of the glandular cell, without causing its death. The apical portion that is shed consists of a part of the cytoplasm and the surrounding plasma membrane, containing the secretory products. This mode of secretion is typical of mammary secretory cells, where the shed cellular portion includes large lipid droplets, proteins and glucids.
- Holocrine glands undergo degeneration of glandular cells after synthesizing and storing the product. The product is released when the plasma membrane ruptures. This is the mode of secretion of sebaceous glands in the skin of mammals. These glands store lipid and wax droplets that are released when the secretory cells die and their membranes rupture.
A given exocrine gland can exhibit several characteristics of morphology and secretion type, so its histological nomenclature should encompass various classification terms as indicated above, such as merocrine mucous unicellular gland, simple alveolar (or acinar) mucous gland, or merocrine serous compound tubuloalveolar gland.
Endocrine glands, which secrete hormones into the internal environment, originate embryonically from lining epithelia and can be either unicellular or multicellular glands. They are classified based on their morphology and secretion product.
- Unicellular endocrine glands remain anchored to the lining epithelium from which they originate, but their basal, secretory pole faces the basement membrane of the epithelium, allowing hormones to be released into the intercellular space or interstitial fluid, or directly into the circulation (blood, hemolymph, etc.).
An example of unicellular endocrine glands is the enteroendocrine system, which consists of numerous endocrine cells dispersed among the lining cells of the digestive tract epithelium in vertebrates. Similar systems composed of unicellular endocrine glands are also found in other organ systems (respiratory, renal, sexual) and in endocrine glands of vertebrates.
Within these systems, there are various types of unicellular endocrine glands that differ in the hormones they secrete, their locations, and their morphology. Initially, these endocrine cells were classified based on their staining characteristics (chromaffin, argentaffin, argyrophilic, metachromatic) and their ability to capture and decarboxylate amines (APUD cells). However, modern immunodetection techniques such as immunoperoxidase staining allow them to be identified based on the type of product they secrete.
From that terminology, regarding structure, the classification of open unicellular endocrine glands remains relevant. In these glands, the apical pole contacts the external environment (for example, the lumen of the stomach), while closed unicellular glands do not reach the surface of the epithelium. Open unicellular endocrine glands often possess microvilli at the apical end, which play a role in capturing stimuli from the external environment and regulating secretion.
- Multicellular endocrine glands form when progenitor cells of endocrine cells sink into the mesenchyme (precursor tissue of connective tissue), forming cellular cords and losing communication with the lining epithelium.
The cellular cords of endocrine cells, along with the surrounding mesenchymal-derived tissues and structures (connective tissue, vascularization), as well as visceral innervation, might be included within other organs. These organs can be glandular (for example, the islets of Langerhans embedded in the exocrine pancreas of mammals) or non-glandular (as is the case of the interrenal endocrine tissue (equivalent to the corticoadrenal), which resides in the kidney of teleost fish).
In other cases, the cords, surrounding tissues, and accompanying structures give rise to endocrine organs, such as the adrenal glands of mammals, the thyroid, or the anterior pituitary gland (adenohypophysis).
Multicellular endocrine glands are histologically organized in two main ways:
- Parenchymal glands, in which endocrine cells form cellular cords that are interposed between numerous blood capillaries. Examples include the islets of Langerhans (endocrine pancreas) or the cortex and medulla of the adrenal glands.
- Follicular glands, like the thyroid, in which secretory cells are arranged to form follicles. These follicles consist of a simple epithelium surrounding a cavity where a precursor of the active hormone is stored.
Based on the biochemical type of hormone they secrete, endocrine cells are classified into:
- Peptide or polypeptide secreting, which contain basophilic or acidophilic granules of varying sizes and ultrastructure. The cytoplasm presents perinuclear basophilic areas corresponding to the development of the rough endoplasmic reticulum. The release of the endocrine granules occurs by exocytosis.
- Steroid secreting, which accumulate lipid droplets, sometimes seasonally, lipid droplets, and the cytoplasm is acidophilic due to the accumulation of mitochondria with tubular cristae, and smooth endoplasmic reticulum tubules involved in the synthesis of steroid hormones. There is no accumulation of steroid hormones in granules and their release occurs through the plasma membrane, which is permeable to lipid products.
- Amine secreting, such as catecholamines (adrenaline, noradrenaline, dopamine) or serotonin, are stored in small cytoplasmic granules that are difficult to observe with routine techniques. Although these cells secrete different biogenic amines, they are grouped under the designation of APUD cells because they can capture and decarboxylate amine precursors (Amine Precursor Uptake and Decarboxylation). The cytoplasm of cells that synthesize and store catecholamines, like those in the adrenal medulla, stains with chromium salts, hence they are categorized as chromaffin cells. Others, such as those storing dopamine, exhibit autofluorescence after formaldehyde fixation. The secretion of catecholamines occurs by exocytosis of the granule contents.
An endocrine gland may contain more than one type of endocrine cells, as seen in the adrenal (suprarenal) glands of mammals, where the cortex contains secretory cells of steroid hormones (corticosteroids), and the medulla harbors chromaffin cells secreting amines (adrenaline and noradrenaline). Similarly, in the thyroid gland, it comprises follicular cells secreting thyroid hormones (T3 and T4), and parafollicular cells (C cells), which are APUD cells (producing serotonin) but also secrete calcitonin (a polypeptide hormone).