Medical School · Year 1 · Histology · includes a quiz and discussion video

Lecture 3: Glandular Epithelium

Unit 1.2: Histology and Basic Tissues

Learning Objectives

By the end of this lecture, students will be able to:

1. Distinguish between exocrine and endocrine glands based on structure and function
2. Classify exocrine glands by their structure (simple vs. compound, tubular vs. acinar)
3. Describe the three mechanisms of secretion: merocrine, apocrine, and holocrine
4. Identify the structure and function of major exocrine glands
5. Describe the histological features of endocrine glands
6. Recognize different gland types in histological sections

Introduction to Glands

Glands are collections of epithelial cells specialized for secretion—the synthesis and release of specific products that serve functions elsewhere in the body. All glands develop from epithelial surfaces during embryonic life through downgrowths of epithelial cells into underlying connective tissue. This common developmental origin explains why glands maintain epithelial characteristics despite their diverse forms and functions.

Glands are fundamentally classified based on their method of releasing secretions. Exocrine glands retain their connection to the surface epithelium through a duct system, delivering their products to body surfaces or organ cavities. Examples include salivary glands (secreting into the oral cavity), sweat glands (secreting onto the skin surface), and the pancreas (secreting digestive enzymes into the duodenal lumen). Endocrine glands, by contrast, lose their connection to the surface during development and instead develop rich vascular networks. They release their products—hormones—directly into the bloodstream for distribution to target organs throughout the body. Examples include the thyroid gland, adrenal glands, and pituitary gland. Some organs contain both exocrine and endocrine components, functioning as mixed glands. The pancreas secretes digestive enzymes through its duct system (exocrine function) while also releasing insulin and glucagon from the islets of Langerhans into the blood (endocrine function).

<image>Panel A: Stage 1 showing continuous surface epithelium as single layer of light pink cuboidal cells with underlying pale blue mesenchyme as developmental starting point. Panel B: Stage 2 showing two parallel downgrowths of epithelial cells extending into the mesenchyme representing early gland development. Panel C: Exocrine gland differentiation with secretory acinus as grape-like cluster of darker cells connected to surface by tubular duct system with arrow showing secretion flowing through duct. Panel D: Endocrine gland differentiation showing isolated cell clusters that lost surface connection surrounded by red sinusoidal capillary network with arrows showing yellow hormones entering bloodstream.</image>

Exocrine Glands: Structural Classification

Exocrine glands vary enormously in complexity, from single cells to elaborate multi-lobed organs. A systematic classification based on structural features provides the vocabulary for describing any exocrine gland.

The simplest exocrine glands consist of single cells. The goblet cell represents the classic unicellular exocrine gland—an individual mucus-secreting cell interspersed among other epithelial cells, particularly in the respiratory and intestinal epithelia. Goblet cells produce and release mucins without forming any organized glandular structure beyond the single cell itself.

Multicellular exocrine glands are classified according to the complexity of their duct systems. Simple glands possess a single, unbranched duct connecting the secretory portion to the epithelial surface. Compound glands have branched duct systems with multiple generations of divisions, creating elaborate drainage networks. The major salivary glands and the pancreas exemplify compound glands.

The shape of the secretory portion provides additional classification criteria. Tubular secretory units are elongated tubes that may be straight, coiled, or branched. Acinar (or alveolar) secretory units are rounded, berry-shaped or flask-shaped structures. Tubuloacinar glands combine both shapes within the same organ.

Combining these features produces a complete classification. Simple tubular glands, such as the intestinal crypts (glands of Lieberkühn), consist of straight tubes opening directly to the epithelial surface. Simple coiled tubular glands, exemplified by eccrine sweat glands, have coiled secretory portions with unbranched ducts. Simple branched tubular glands, like gastric glands, have multiple branching secretory tubules sharing a common opening. Simple acinar glands, including sebaceous glands, have rounded secretory units with short ducts. Compound tubular glands, such as Brunner's glands of the duodenum, have tubular secretory units with branched duct systems. Compound acinar glands, like the parotid gland, have rounded acini drained by branched ducts. Compound tubuloacinar glands, including the submandibular gland and exocrine pancreas, combine tubular and acinar secretory units in the same organ.

<image>Panel A: Simple glands showing simple tubular as straight tube from surface, simple coiled tubular with coiled secretory portion in dermis, and simple branched tubular with branching tubes sharing single opening. Panel B: Simple acinar showing round secretory unit with short duct and simple branched acinar with multiple acini connected to single duct with blue ducts and pink secretory units. Panel C: Compound glands showing compound tubular with tubular secretory units and branched duct system and compound acinar with spherical acini arranged in clusters around branching ducts. Panel D: Compound tubuloacinar showing mix of tubular and acinar units with complex branching ducts with anatomical examples and color legend distinguishing secretory portions from duct portions.</image>

Mechanisms of Secretion

The manner in which secretory cells release their products varies among different gland types, with three mechanisms recognized: merocrine, apocrine, and holocrine. These mechanisms differ in whether and how much of the cell itself becomes part of the secretion.

Merocrine secretion (also called eccrine secretion) is the most common mechanism and involves release of secretory products by exocytosis. Membrane-bound secretory vesicles fuse with the apical plasma membrane, discharging their contents into the gland lumen while the membrane is recycled. The secretory cell remains entirely intact and continues functioning. Merocrine secretion occurs in salivary glands, the exocrine pancreas, eccrine sweat glands, lacrimal glands, and most other exocrine glands. The term "merocrine" derives from the Greek for "part secretion," reflecting that only the vesicle contents—not any part of the cell itself—are released.

Apocrine secretion involves the release of secretion along with a portion of the apical cytoplasm. The apical region of the cell pinches off as a membrane-bound vesicle containing the secretory product mixed with some cytoplasm. The cell survives and regenerates its apical portion. Traditionally, apocrine secretion was attributed to mammary glands (for the lipid component of milk) and apocrine sweat glands. However, modern evidence suggests true apocrine secretion may be more limited than historically believed, with some apparent apocrine appearances representing fixation artifacts. The lipid droplets in mammary secretion may be released by a mechanism distinct from classic apocrine secretion.

Holocrine secretion represents the most extreme mechanism: the entire cell becomes the secretory product. Cells accumulate secretory material in their cytoplasm, then undergo programmed death and disintegration, releasing their contents as the secretion. Continuous replacement of lost cells from a proliferative basal layer maintains gland function. Sebaceous glands are the classic example of holocrine glands—basal cells divide, daughter cells fill with lipid droplets as they move toward the center of the acinus, and fully mature cells rupture to release sebum. The term "holocrine" derives from the Greek for "whole secretion."

<image>Panel A: Merocrine secretion showing tall cell with yellow secretory vesicles in apical cytoplasm then vesicles fusing with apical membrane releasing contents as yellow droplets while cell remains completely intact with vesicle-membrane fusion inset. Panel B: Apocrine secretion showing cell with orange secretory product accumulated in bulging apical region then apical portion pinching off as membrane-bound vesicle while basal portion with nucleus remains attached with dotted regeneration line. Panel C: Holocrine secretion cross-section through sebaceous gland showing small basal cells with prominent nuclei at periphery progressing inward to enlarged cells filled with white lipid vacuoles with pyknotic nuclei. Panel D: Center of holocrine gland where cells have completely disintegrated releasing yellow lipid contents into duct with arrows indicating direction of cell maturation and movement.</image>

Classification by Secretory Product

The nature of the secretory product provides another basis for classifying exocrine glands, with important histological correlates that aid microscopic identification.

Serous glands produce a watery, protein-rich secretion typically containing enzymes. The serous secretory cell has a characteristic appearance: pyramidal shape with a round, centrally located nucleus. The cytoplasm shows marked basophilia in the basal region due to abundant rough endoplasmic reticulum engaged in protein synthesis. The apical cytoplasm contains secretory (zymogen) granules that may appear eosinophilic or refractile. Serous cells typically form small, rounded acini with narrow lumens. Examples of serous glands include the parotid salivary gland, the exocrine pancreas (acinar cells), and the lacrimal glands. Serous secretions flow readily and contain digestive enzymes, antimicrobial proteins, or other functional proteins.

Mucous glands produce a viscous, gel-like secretion rich in mucins—large glycoproteins that become highly hydrated and form the protective mucus coating many epithelial surfaces. Mucous secretory cells have a distinctive appearance quite different from serous cells. The nucleus is flattened and pressed against the basal cell membrane because accumulated mucin granules distend the apical and central cytoplasm. The cytoplasm appears pale or empty in H&E-stained sections because mucins are lost during routine processing. However, mucins stain intensely with the periodic acid-Schiff (PAS) reaction due to their carbohydrate content. Mucous cells tend to form tubular secretory units with wider lumens than serous acini. The sublingual salivary gland is predominantly mucous, as are many of the minor salivary glands.

Mixed glands (seromucous glands) contain both serous and mucous cells within the same organ. A characteristic feature of mixed glands is the serous demilune—a crescent-shaped cap of serous cells partially surrounding mucous acini. Historically, these demilunes were thought to represent distinct compartments, but recent studies using rapid fixation techniques suggest that demilunes may partly be artifacts of slower fixation, with serous and mucous cells more intermingled in living tissue. Regardless, the presence of both cell types is genuine. The submandibular salivary gland is the classic example of a mixed gland, containing both serous and mucous acini along with serous demilunes.

<image>Panel A: Serous acini at 600x showing cluster of three acini with pyramidal cells around tiny lumens displaying purple round central nuclei, blue-purple basophilic basal cytoplasm from abundant RER, and bright pink apical zymogen granules. Panel B: Mucous acini showing two tubules with flattened basal nuclei pressed against basement membrane and pale foamy cytoplasm appearing white to very pale pink with wider lumens than serous acini. Panel C: PAS-stained inset of mucous acini showing intense magenta staining highlighting mucin content that was extracted in standard H&E processing. Panel D: Mixed acini showing pale mucous acinus with basal nuclei capped by crescent-shaped serous demilune of darker cells with round nuclei wrapping around outer aspect with visible draining duct.</image>

Major Exocrine Glands

Salivary Glands

The three pairs of major salivary glands—parotid, submandibular, and sublingual—demonstrate the spectrum from pure serous to predominantly mucous secretion. Understanding their histological differences aids both identification and appreciation of functional diversity.

The parotid gland is the largest salivary gland, located anterior to the external ear. It is purely serous, consisting entirely of serous acini that produce a watery secretion rich in salivary amylase for starch digestion and various antimicrobial proteins. Histologically, the parotid shows uniformly dark-staining acini with pyramidal cells containing round central nuclei and basophilic cytoplasm with apical zymogen granules. A notable feature of aging parotid glands is the progressive infiltration of adipose tissue between the secretory lobules. The parotid duct (Stensen's duct) empties into the oral cavity opposite the second upper molar.

The submandibular gland lies beneath the mandible and is a mixed gland that is predominantly serous. It contains both serous and mucous acini, along with serous demilunes capping some mucous tubules. The mixture gives the submandibular a more varied histological appearance than the uniform parotid. The submandibular duct (Wharton's duct) opens at the sublingual papilla on the floor of the mouth.

The sublingual gland is the smallest major salivary gland, located beneath the tongue. It is predominantly mucous, with most secretory units being mucous tubules, though some serous demilunes and mixed acini are present. Histologically, the sublingual appears much paler than the other major salivary glands due to the predominance of mucous cells. Multiple small ducts (ducts of Rivinus) open along the sublingual fold, with some joining to form a larger duct (Bartholin's duct).

All major salivary glands share certain histological features. Intercalated ducts are small ducts lined by simple cuboidal epithelium that connect acini to larger ducts. Striated ducts are larger intralobular ducts with distinctive basal striations caused by infoldings of the basal plasma membrane containing numerous mitochondria—these cells modify saliva composition through ion exchange, absorbing sodium and secreting potassium and bicarbonate. Myoepithelial cells surround acini and intercalated ducts, contracting to assist secretion.

<image>Panel A: Parotid gland at 200x showing uniform dark-staining serous acini with round nuclei and basophilic-eosinophilic cytoplasm plus clear fat cells between lobules and labeled intercalated and striated ducts. Panel B: Submandibular gland showing mixture with predominant dark serous acini, scattered pale mucous tubules with flattened basal nuclei, and serous demilunes as dark crescents capping pale mucous units. Panel C: Sublingual gland showing predominantly pale mucous tubules with characteristic foamy cytoplasm and basal nuclei with only occasional darker serous components appearing much lighter overall. Panel D: Higher magnification inset at 25 micrometer scale showing typical demilune in detail with prominent striated duct and 100 micrometer scale bars for main panels.</image>

Exocrine Pancreas

The exocrine pancreas constitutes the vast majority of pancreatic tissue and functions as a compound acinar gland producing digestive enzymes. The secretory units are serous acini composed of pyramidal cells with basal basophilia (abundant rough ER for protein synthesis) and prominent apical zymogen granules containing the precursors of digestive enzymes including trypsinogen, chymotrypsinogen, lipase, and amylase.

A distinctive feature of pancreatic acini is the presence of centroacinar cells—pale-staining cells located within the center of acini that represent the beginning of the intercalated duct system extending into the acinar lumen. These cells are not seen in salivary gland acini and help distinguish pancreatic from salivary tissue. Centroacinar cells and intercalated duct cells secrete the bicarbonate-rich fluid component of pancreatic juice, while acinar cells contribute the enzyme component.

Sweat Glands

Eccrine sweat glands are simple coiled tubular glands found throughout the skin, most densely on the palms, soles, and forehead. They function in thermoregulation through evaporative cooling. The secretory portion lies coiled in the dermis and consists of three cell types: dark cells (glycoprotein-secreting), clear cells (watery secretion), and myoepithelial cells. The duct extends through the dermis and epidermis to open directly onto the skin surface. Eccrine sweat glands use merocrine secretion.

Apocrine sweat glands are found in the axillae, perianal region, and areolae. They are larger than eccrine glands with wider lumens and open into hair follicles rather than directly onto the skin surface. Their secretion is thicker and contains proteins that bacteria can metabolize to produce body odor. Despite their name, whether these glands use true apocrine secretion is debated.

Sebaceous Glands

Sebaceous glands are simple branched acinar glands that produce sebum—an oily substance containing lipids that lubricates hair and skin, provides antimicrobial activity, and prevents water loss. They are almost always associated with hair follicles, emptying into the upper portion of the follicle. Sebaceous glands represent the classic example of holocrine secretion: basal cells divide, and daughter cells progressively fill with lipid droplets as they move toward the center of the acinus, eventually disintegrating to release their contents. Histologically, sebaceous glands show the characteristic progression from small peripheral cells with visible nuclei to enlarged central cells filled with lipid vacuoles with small, pyknotic nuclei.

Endocrine Glands

Endocrine glands lack ducts and release their products—hormones—directly into the bloodstream through fenestrated capillaries that intimately surround the secretory cells. This arrangement contrasts sharply with the duct-dependent organization of exocrine glands.

Endocrine glands display two fundamental organizational patterns. In the cord and clump arrangement, secretory cells are organized as anastomosing cords or irregular clusters surrounded by a rich network of sinusoidal capillaries. This pattern maximizes the contact between secretory cells and blood vessels, facilitating rapid hormone release. Examples include the adrenal cortex, where cells arranged in cords produce steroid hormones; the anterior pituitary, where various cell types in clusters produce trophic hormones; and the parathyroid glands, where chief cells in sheets and cords produce parathyroid hormone.

In the follicular arrangement, secretory cells surround a central lumen that stores the secretory product in a modified form until release is triggered. The thyroid gland exemplifies this pattern: follicular cells surround lumens filled with colloid, a gel-like material containing thyroglobulin from which thyroid hormones are cleaved when needed. This arrangement allows hormone storage and regulated release rather than continuous secretion.

Major endocrine glands each have distinctive histological features. The thyroid gland consists of follicles of varying sizes lined by simple cuboidal to columnar epithelium, with the follicle lumen containing pink-staining colloid; C cells (parafollicular cells) producing calcitonin lie between follicles. The parathyroid glands contain chief cells (small, with pale cytoplasm producing PTH) and oxyphil cells (larger, with eosinophilic cytoplasm and unknown function). The adrenal cortex shows three zones—zona glomerulosa (producing aldosterone), zona fasciculata (producing cortisol, cells appearing pale and lipid-laden), and zona reticularis (producing androgens)—while the adrenal medulla contains chromaffin cells producing catecholamines. The anterior pituitary contains chromophobes (pale, sparse cytoplasm) and chromophils subdivided into acidophils (producing growth hormone and prolactin) and basophils (producing ACTH, TSH, FSH, LH). The posterior pituitary stores hormones produced in the hypothalamus, appearing as Herring bodies (axonal dilations containing hormone) among pituicytes (glial-like supporting cells). The pancreatic islets of Langerhans appear as pale-staining islands within the darker exocrine tissue, containing alpha cells (glucagon), beta cells (insulin), delta cells (somatostatin), and other minor cell types.

<image>Panel A: Cord and clump pattern in adrenal cortex showing secretory cells arranged in columns with yellow zona glomerulosa at top, pale pink lipid-rich zona fasciculata in middle, and darker pink zona reticularis below. Panel B: Sinusoidal capillaries as thin red fenestrated channels weaving between cell cords with ultrastructure inset showing steroid-secreting cell releasing hormone triangles directly into bloodstream. Panel C: Follicular pattern in thyroid showing circular follicles of varying sizes with ring of pink cuboidal epithelial cells surrounding central lumen filled with pale pink-orange colloid. Panel D: Follicular cell detail inset showing apical microvilli extending into colloid, endocytosed colloid droplets, basal hormone release into capillary, and C cell in interfollicular space producing calcitonin.</image>

Myoepithelial Cells

Myoepithelial cells are specialized contractile cells found in many exocrine glands, positioned between the secretory or duct epithelium and the basement membrane. They share characteristics of both epithelial cells (origin, location) and smooth muscle cells (contractile proteins).

Structurally, myoepithelial cells are stellate or spindle-shaped with multiple processes that wrap around acini and ducts. They contain actin and myosin filaments and express smooth muscle actin, which can be demonstrated immunohistochemically. When surrounding acini, their processes embrace the secretory unit like an octopus encircling a ball.

Functionally, myoepithelial cells contract in response to neural or hormonal stimulation, squeezing the secretory unit to expel contents into the duct system. This is particularly important in glands that must respond rapidly to stimulation, such as salivary glands (responding to food) and mammary glands (responding to suckling).

Histologically, myoepithelial cells can be difficult to identify in routine H&E sections because they are flattened and their nuclei blend with those of adjacent cells. Clues to their presence include small, dark, flattened nuclei at the periphery of acini, oriented parallel to the basement membrane. Immunohistochemistry for smooth muscle actin, calponin, or p63 reliably identifies them.

Myoepithelial cells are clinically relevant in breast pathology, where their presence around proliferating epithelium indicates a benign (in situ) process, while their absence suggests invasion through the basement membrane—a hallmark of malignancy.

<image>Panel A: Longitudinal section through salivary gland acinus with tall pyramidal secretory cells showing round nuclei and pink-purple apical secretory granules connected to intercalated duct. Panel B: Green-yellow myoepithelial cells as flattened stellate cells with multiple processes embracing secretory unit lying between epithelium and magenta basement membrane. Panel C: Three-dimensional inset showing myoepithelial cell wrapped around acinus with nucleus and 6-8 arm-like processes spreading like basket plus contracted state inset with arrows showing acinus compression expelling secretory material. Panel D: Immunohistochemistry showing myoepithelial cells stained brown positive for smooth muscle actin while secretory cells remain unstained demonstrating selective marker identification.</image>

Clinical Correlations

Sjögren syndrome is an autoimmune disease in which the immune system attacks exocrine glands, particularly the salivary and lacrimal glands. Lymphocytic infiltration progressively destroys secretory tissue, leading to dry mouth (xerostomia) and dry eyes (keratoconjunctivitis sicca). Patients experience difficulty swallowing, increased dental caries, and ocular discomfort. Biopsy of minor salivary glands from the lower lip shows lymphocytic aggregates replacing normal acinar tissue. Sjögren syndrome may occur in isolation (primary) or in association with other autoimmune diseases such as rheumatoid arthritis (secondary).

Salivary gland tumors are relatively common, with most arising in the parotid gland. Pleomorphic adenoma (benign mixed tumor) is the most common salivary gland tumor, containing both epithelial elements and myxoid/chondroid stromal components. Despite being benign, it can recur if incompletely excised. Warthin tumor (papillary cystadenoma lymphomatosum) occurs almost exclusively in the parotid, contains oncocytic epithelium with lymphoid stroma, and has a risk of bilateral occurrence. Mucoepidermoid carcinoma is the most common malignant salivary gland tumor, containing mucus-secreting cells, epidermoid cells, and intermediate cells.

Cystic fibrosis results from mutations in the CFTR gene encoding a chloride channel essential for hydrating exocrine secretions. Defective chloride (and secondarily bicarbonate) secretion leads to abnormally thick, viscous secretions that obstruct ducts and damage organs. In the pancreas, thick secretions block ducts, leading to destruction of exocrine tissue and eventually endocrine tissue, causing malabsorption and diabetes. In the lungs, thick mucus impairs mucociliary clearance and promotes infection. In sweat glands, defective chloride reabsorption causes elevated sweat chloride—the basis of the diagnostic sweat test.

Acne vulgaris involves sebaceous glands and their associated hair follicles. Hormonal stimulation (androgens) increases sebum production. Abnormal keratinization of the follicular epithelium creates a plug that obstructs the follicle opening (comedone). Accumulated sebum behind the obstruction supports proliferation of Cutibacterium acnes (formerly Propionibacterium acnes), which metabolizes sebum and triggers inflammation. Rupture of the distended follicle wall releases contents into the dermis, inciting a more intense inflammatory response.

Summary

Glands are epithelial cells specialized for secretion, derived from surface epithelia during development. Exocrine glands maintain duct connections to surfaces, while endocrine glands lose this connection and secrete hormones into the bloodstream.

Exocrine glands are classified by structural complexity (simple versus compound ducts), by the shape of secretory portions (tubular, acinar, or tubuloacinar), and by the nature of their secretion (serous, mucous, or mixed). Three secretion mechanisms exist: merocrine (exocytosis with cell intact), apocrine (apical cytoplasm released), and holocrine (entire cell becomes secretion).

The major salivary glands illustrate the spectrum of secretory types. The parotid is purely serous, producing watery enzyme-rich saliva. The submandibular is mixed with serous predominance, featuring characteristic serous demilunes. The sublingual is predominantly mucous, producing viscous secretion. All contain striated ducts for electrolyte modification and myoepithelial cells for secretion assistance.

Endocrine glands are organized as cords and clumps (adrenal cortex, pituitary, parathyroid) or as follicles (thyroid). Rich capillary networks facilitate hormone release into the circulation.

Clinical disorders affecting glands include autoimmune destruction (Sjögren syndrome), neoplasia (pleomorphic adenoma, mucoepidermoid carcinoma), genetic defects affecting secretion (cystic fibrosis), and inflammatory conditions (acne).

Key Terms

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