THE BASICS OF ENDOCRINE GLAND HISTOLOGY AND EMBRYOLOGY

1. Development of Endocrine Glands

Endocrine glands arise from different embryonic germ layers (ectoderm, mesoderm, and endoderm) and undergo complex morphogenetic movements, proliferation, and differentiation processes during embryonic and fetal development.

1.1 Thyroid Gland Development

The thyroid gland is among the first endocrine glands to develop.

• Step 1: Origin (Week 3-4): Development begins around the 3rd to 4th week of gestation as a median endodermal thickening in the floor of the primitive pharynx, specifically between the tuberculum impar and the copula, in the region that will become the posterior part of the tongue. This thickening rapidly forms a small pouch or diverticulum.
• Step 2: Descent: This diverticulum elongates, forming the thyroglossal duct, and descends caudally through the neck, passing ventral to the hyoid bone and laryngeal cartilages.
• Step 3: Bifurcation and Formation: The distal end of the thyroglossal duct expands and bifurcates into two lobes (future left and right lobes of the thyroid gland). The isthmus, connecting the two lobes, develops from the portion of the duct just superior to the bifurcated lobes.
• Step 4: Migration and Location: By the 7th week, the thyroid gland reaches its definitive position in the anterior neck, inferior to the larynx and trachea.
• Step 5: Duct Regression: The thyroglossal duct typically degenerates and disappears between the 7th and 10th weeks. Remnants can persist, leading to thyroglossal duct cysts or fistulas.
• Step 6: Follicle Formation and Differentiation: Endodermal cells differentiate to form cellular cords, which then break up into follicles. Colloid begins to appear in the follicular lumens around 11 weeks, and iodine uptake and hormone synthesis start shortly thereafter. Parafollicular (C) cells, which produce calcitonin, are derived separately from neural crest cells that migrate into the developing thyroid from the ultimobranchial bodies (structures arising from the 4th and 5th pharyngeal pouches).

1.2 Parathyroid Gland Development

The parathyroid glands develop from the pharyngeal pouches, which are endodermal outpouchings of the lateral walls of the pharynx.

• Step 1: Origin from Pharyngeal Pouches (Week 5-6): The superior parathyroid glands develop from the dorsal portion of the 4th pharyngeal pouch. The inferior parathyroid glands develop from the dorsal portion of the 3rd pharyngeal pouch.
• Step 2: Migration with Other Structures: The structures derived from the 3rd pouch (thymus ventrally, inferior parathyroids dorsally) migrate caudally. The structures from the 4th pouch (superior parathyroids dorsally, ultimobranchial body ventrally) also migrate, but less extensively.
• Step 3: Relative Positioning: Because the 3rd pouch structures migrate further caudally than the 4th pouch structures, the inferior parathyroids (from the 3rd pouch) end up located inferior to the superior parathyroids (from the 4th pouch), despite originating from a more superior pouch. They typically come to rest on the posterior surface of the thyroid gland.
• Step 4: Cell Differentiation: Principal (chief) cells, which synthesize and secrete parathyroid hormone (PTH), and oxyphil cells differentiate within the parathyroid tissue.

1.3 Pituitary Gland (Hypophysis) Development

The pituitary gland has a unique dual origin, arising from two different embryonic sources that later fuse.

• Step 1: Origins (Week 4):
  • The anterior pituitary (adenohypophysis) originates from an ectodermal outpouching of the roof of the primitive mouth (stomodeum), known as Rathke’s pouch.
  • The posterior pituitary (neurohypophysis) originates from a neuroectodermal downgrowth from the floor of the diencephalon (part of the developing brain), called the infundibulum.
• Step 2: Migration and Elongation: Rathke’s pouch elongates rostrally towards the developing brain, detaching from the oral ectoderm around the 6th week. The infundibulum grows caudally towards Rathke’s pouch.
• Step 3: Fusion and Differentiation: The two components meet and fuse. The wall of Rathke’s pouch facing the infundibulum thickens dramatically to form the pars distalis, the largest part of the adenohypophysis. A small part of Rathke’s pouch that wraps around the infundibular stalk forms the pars tuberalis. The posterior wall of the pouch remains thin and forms the pars intermedia (often rudimentary in humans). The infundibulum differentiates into the pars nervosa (posterior lobe) and the infundibular stalk (pituitary stalk).
• Step 4: Capsule Formation: Connective tissue from the surrounding mesenchyme forms a capsule around the developing gland.

1.4 Adrenal Gland Development

The adrenal gland also has a dual origin, with the cortex and medulla developing separately from different germ layers.

• Step 1: Cortical Origin (Week 5): The adrenal cortex develops from intermediate mesoderm located between the root of the mesentery and the developing gonad. Cells from this region form a mass called the fetal cortex (or primitive cortex).
• Step 2: Medullary Origin (Week 7): The adrenal medulla originates from neural crest cells. These cells migrate from the adjacent sympathetic ganglia into the center of the developing fetal cortex.
• Step 3: Formation of Permanent Cortex (Later Fetal Period): A second wave of mesodermal cells from the same area surrounds the fetal cortex, forming the definitive (permanent) cortex.
• Step 4: Differentiation: The fetal cortex occupies most of the gland volume during fetal life and produces steroid hormones essential for fetal survival. After birth, the fetal cortex regresses, and the permanent cortex differentiates into the characteristic three zones: zona glomerulosa, zona fasciculata, and zona reticularis. The neural crest cells in the center differentiate into chromaffin cells, which synthesize and secrete catecholamines (epinephrine and norepinephrine).

1.5 Pancreas Development

The pancreas, both exocrine and endocrine, develops from endodermal buds arising from the primitive foregut.

• Step 1: Bud Formation (Week 4): Two pancreatic buds appear: a larger dorsal bud and a smaller ventral bud. Both are extensions of the endodermal lining of the duodenum. The dorsal bud arises directly from the dorsal wall, while the ventral bud arises from the bile duct diverticulum.
• Step 2: Rotation and Fusion: As the duodenum rotates due to stomach growth, the ventral pancreatic bud is carried dorsally and rotates posteriorly to lie below and behind the dorsal bud. The two buds then fuse, typically around the 6th week.
• Step 3: Duct System Formation: The main pancreatic duct (duct of Wirsung) forms from the duct of the ventral bud and the distal part of the dorsal bud duct. The proximal part of the dorsal bud duct may persist as the accessory pancreatic duct (duct of Santorini).
• Step 4: Differentiation: Endodermal cells give rise to both the exocrine (acinar cells and duct system) and endocrine components (islets of Langerhans). The islets differentiate from clusters of cells budding off from the developing ducts. Insulin secretion begins around week 10, and other islet hormones (glucagon, somatostatin, pancreatic polypeptide) differentiate later.

2. Microscopic Structure and Cells of the Pituitary Gland

The pituitary gland (hypophysis) is located at the base of the brain, suspended from the hypothalamus by the pituitary stalk (infundibulum), and housed within the sella turcica of the sphenoid bone. Microscopically, it is clearly divided into two main parts with distinct origins and structures: the adenohypophysis (anterior pituitary) and the neurohypophysis (posterior pituitary).

2.1 Adenohypophysis (Anterior Pituitary)

The adenohypophysis develops from oral ectoderm (Rathke’s pouch) and is responsible for synthesizing and secreting numerous peptide hormones that regulate other endocrine glands and various body functions. It is typically organized into three parts:

• Pars Distalis: This is the largest and anterior-most part, forming the bulk of the adenohypophysis. It is characterized by cords and nests of endocrine cells supported by a reticular connective tissue framework and surrounded by a rich network of sinusoidal capillaries. The cells are classically classified based on their staining properties with histological dyes:
  • Chromophils: These cells stain intensely due to the presence of secretory granules containing hormones.
    • Acidophils: Stain with acidic dyes (like eosin), appearing reddish or pink. They constitute about 40% of the cells.
      • Somatotrophs: Produce Growth Hormone (GH).
      • Lactotrophs (Mammotrophs): Produce Prolactin (PRL).
    • Basophils: Stain with basic dyes (like hematoxylin), appearing bluish or purple. They constitute about 10% of the cells.
      • Corticotrophs: Produce Adrenocorticotropic Hormone (ACTH) and Melanocyte-Stimulating Hormone (MSH; in pars intermedia remnants).
      • Thyrotrophs: Produce Thyroid-Stimulating Hormone (TSH).
      • Gonadotrophs: Produce Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH).
  • Chromophobes: These cells constitute about 50% of the cells and stain weakly or not at all. They are typically smaller cells with less cytoplasm. They are thought to represent either degranulated chromophils that have released their hormones, or undifferentiated stem cells, or potentially resting chromophils.
• Pars Intermedia: A narrow band located between the pars distalis and the pars nervosa. In humans, it is often rudimentary, consisting of cysts (Rathke’s cysts) lined by cuboidal epithelium and scattered basophils (corticotrophs) that produce ACTH and peptides related to MSH.
• Pars Tuberalis: A funnel-shaped region that wraps around the infundibular stalk. It consists mainly of gonadotrophs and contains portal vessels of the hypophyseal portal system, but its precise function is less understood compared to the pars distalis.

The adenohypophysis lacks direct neural connections from the hypothalamus but is regulated by releasing and inhibiting hormones transported from the hypothalamus via the hypophyseal portal system, a specialized capillary network.

2.2 Neurohypophysis (Posterior Pituitary)

The neurohypophysis develops from neuroectoderm (infundibulum) and is essentially an extension of the brain. It does not synthesize hormones but stores and releases hormones produced by neurosecretory neurons in the hypothalamus. It consists of two parts:

• Pars Nervosa: The larger, posterior part. Microscopically, it is composed of unmyelinated axons of neurosecretory neurons originating from the supraoptic and paraventricular nuclei of the hypothalamus. These axons form the hypothalamo-hypophyseal tract.
  • Pituicytes: These are the characteristic glial-like cells of the pars nervosa. They are branched cells with irregular nuclei and are the predominant cell type other than axons. They function as supporting cells for the axons and blood vessels.
  • Herring Bodies: These are dilations or swellings along the axons where neurosecretory material (hormones bound to carrier proteins, neurophysins) is stored before release into the bloodstream. The hormones stored and released here are Antidiuretic Hormone (ADH or vasopressin) and Oxytocin.
• Infundibulum (Pituitary Stalk): Connects the pars nervosa to the hypothalamus. It contains the axons of the hypothalamo-hypophyseal tract and the portal vessels.

The neurohypophysis is supplied by capillaries that receive hormones stored in Herring bodies, allowing for their release directly into the systemic circulation.

3. Microscopic Structure of the Thyroid Gland

The thyroid gland, located in the anterior neck, is encased in a connective tissue capsule from which septa extend into the parenchyma, dividing it into lobules. The functional unit of the thyroid gland is the thyroid follicle.

3.1 Thyroid Follicle

The thyroid follicle is the striking and defining feature of thyroid histology.

• Structure: Follicles are spherical or oval structures of varying sizes. Each follicle consists of a central lumen filled with a gel-like substance called colloid, surrounded by a single layer of epithelial cells, the follicular cells.
• Colloid: The lumen contains colloid, which is primarily composed of synthesized and stored thyroglobulin, a large glycoprotein that serves as the precursor protein for the thyroid hormones. The amount of colloid in the lumen varies with the activity level of the gland.
• Basement Membrane: Each thyroid follicle is surrounded by a basement membrane, external to the follicular cells.
• Vascular Supply: The spaces between the follicles are filled with a delicate reticular connective tissue that contains a dense network of fenestrated capillaries, which are essential for supplying raw materials to the follicular cells and collecting secreted hormones. Lymphatic vessels are also present.

3.2 Follicular Cells

These are the principal cells lining the thyroid follicle lumen.

• Appearance: They are typically cuboidal epithelial cells, but their shape varies depending on the gland’s activity state. In an inactive gland, they may appear flattened (squamous). In a highly active gland, they become taller (columnar).
• Nucleus and Cytoplasm: They have round, centrally located nuclei. Their cytoplasm contains organelles involved in protein synthesis and secretion, including abundant rough endoplasmic reticulum, a prominent Golgi apparatus, lysosomes, and secretory vesicles containing thyroglobulin.
• Function: Follicular cells are responsible for synthesizing thyroglobulin and thyroid hormones (thyroxine, T4, and triiodothyronine, T3). This complex process involves the uptake of iodide from the blood, synthesis of thyroglobulin, iodination of tyrosine residues on thyroglobulin within the colloid, coupling of iodinated tyrosines, and finally, endocytosis of iodinated thyroglobulin, cleavage of T3/T4, and their release into the bloodstream.

3.3 Parafollicular Cells (C Cells)

These cells are distinct from follicular cells in origin, location, and function.

• Origin: Derived from neural crest cells via the ultimobranchial bodies.
• Location: Located individually or in small clusters within the basement membrane of the thyroid follicle, or in the interfollicular connective tissue. Importantly, they are usually not part of the follicular epithelium lining the lumen, and they do not have direct contact with the colloid.
• Appearance: Generally larger than follicular cells, with pale-staining cytoplasm and eccentric nuclei. Electron microscopy reveals abundant small, membrane-bound granules containing their secretory product.
• Function: Parafollicular cells secrete calcitonin, a hormone that helps regulate calcium metabolism by lowering blood calcium levels. Calcitonin acts primarily on osteoclasts, inhibiting bone resorption. Their secretion is stimulated by high blood calcium levels.

In summary, the thyroid gland’s structure is elegantly designed around the thyroid follicle, where follicular cells produce and store thyroid hormones in the colloid, while interspersed parafollicular cells contribute to calcium homeostasis via calcitonin.

Conclusion

The development of the endocrine glands highlights the complex orchestration of cellular migration, proliferation, and differentiation originating from all three embryonic germ layers, resulting in functionally specialized tissues. The microscopic structures of glands like the pituitary and thyroid reveal intricate organizations of secretory cells, supporting elements, and vascular networks, meticulously arranged to synthesize, store, and release hormones that govern vital bodily functions. A thorough understanding of these developmental processes and microscopic architectures is essential for comprehending endocrine physiology and pathology.

1. The Parathyroid Glands: Guardians of Calcium Homeostasis

The parathyroid glands are small endocrine glands located in the neck, typically situated on the posterior surface of the thyroid gland. Despite their size, they play a critical role in regulating calcium and phosphate levels in the blood through the secretion of parathyroid hormone (PTH).

1.1. Overall Microscopic Structure

Microscopically, each parathyroid gland is encased in a thin connective tissue capsule. Delicate septa, extensions of the capsule, penetrate the gland, dividing the parenchyma (the functional tissue) into irregular lobules or cords, although this lobulation is often indistinct compared to other glands.

The parenchyma is composed primarily of clusters or cords of cells, interspersed with a rich network of fenestrated capillaries and reticular fibers. A characteristic feature, particularly in older individuals, is the presence of numerous adipocytes (fat cells) within the stroma, which can constitute up to 50% of the gland volume by late adulthood.

1.2. Cellular Composition

The parathyroid gland parenchyma contains two main cell types:

• Chief Cells (Principal Cells): These are the most abundant and functionally significant cells of the parathyroid gland.
  • Morphology: Chief cells are relatively small, polygonal cells, measuring about 7-10 µm in diameter. In standard hematoxylin and eosin (H&E) staining, they typically possess a pale eosinophilic or slightly basophilic cytoplasm and a round, centrally located, basophilic nucleus.
  • Functional States: Chief cells exist in different functional states.
    • Inactive Chief Cells: Contain relatively few organelles involved in protein synthesis and secretion (e.g., sparse rough endoplasmic reticulum, few Golgi complexes) and may contain glycogen granules. Their cytoplasm appears paler.
    • Active Chief Cells: Exhibit features indicative of active protein synthesis and secretion, including abundant rough endoplasmic reticulum, well-developed Golgi complexes, and secretory granules containing PTH. Their cytoplasm may appear slightly more basophilic due to the RER.
  • Arrangement: Chief cells are typically arranged in cords or clusters, closely associated with capillaries, allowing for rapid hormone secretion into the bloodstream.
  • Function: Chief cells are responsible for synthesizing and secreting parathyroid hormone (PTH) in response to low blood calcium levels. PTH acts on bone (stimulating osteoclast activity to release calcium), kidneys (increasing calcium reabsorption and phosphate excretion), and indirectly on the intestine (enhancing calcium absorption via activation of Vitamin D) to raise blood calcium.
• Oxyphil Cells: These are larger cells, about 10-15 µm in diameter, and are less numerous than chief cells.
  • Morphology: Oxyphil cells are characterized by their distinctive acidophilic (eosinophilic) cytoplasm, which stains intensely pink with eosin in H&E preparations. This striking eosinophilia is due to the massive accumulation of mitochondria within the cytoplasm. They have a smaller, darker, and often pyknotic (shrunken) nucleus compared to chief cells.
  • Arrangement: Oxyphil cells often appear singly but tend to increase in number with age and frequently form small nests or clusters, particularly in older individuals. They are rarely seen before puberty.
  • Function: The precise function of oxyphil cells remains unclear. They do not appear to synthesize or secrete significant amounts of PTH. Some theories suggest they may be transitional forms of chief cells, perhaps aged or exhausted cells, or that they play a supportive metabolic role due to their abundant mitochondria.

In summary, the parathyroid gland is characterized by cords of small, pale chief cells responsible for PTH production, interspersed with larger, acidophilic oxyphil cells, all supported by a vascular connective tissue stroma containing adipocytes.

2. The Adrenal Glands: Masters of Stress and Metabolism

The adrenal glands, located superior to the kidneys, are retroperitoneal organs. Each gland is composed of two functionally and embryologically distinct regions: an outer cortex and an inner medulla. These regions produce different sets of hormones vital for regulating stress responses, metabolism, blood pressure, and electrolyte balance.

2.1. Overall Microscopic Structure

The adrenal gland is covered by a dense connective tissue capsule. Connective tissue trabeculae extend inward from the capsule, carrying blood vessels and nerves, but they do not divide the gland into distinct lobules. The parenchyma is clearly demarcated into the outer cortex and the inner medulla, each possessing a unique cellular arrangement and composition. The gland receives a rich blood supply, essential for delivering hormones to the circulation.

2.2. The Adrenal Cortex: Steroid Hormone Synthesis

The adrenal cortex is the larger, outer portion of the gland. It is responsible for synthesizing steroid hormones (corticosteroids and androgens) and is histologically divided into three concentric zones based on the arrangement of its cells and their primary secretory product:

• Zona Glomerulosa (ZG):
  • Location: The outermost layer of the cortex, directly beneath the capsule.
  • Cell Arrangement: Cells are arranged in rounded or oval clusters (glomeruli), separated by thin connective tissue septa and capillaries. This arrangement gives the zone its name (glomerulus meaning “little ball”).
  • Cell Morphology: Cells are relatively small, cuboidal to columnar, with round nuclei and cytoplasm that contains moderate amounts of lipid droplets, giving it a somewhat foamy or vacuolated appearance in H&E. They have a prominent smooth endoplasmic reticulum (SER), characteristic of steroid-producing cells.
  • Function: The primary site of mineralocorticoid synthesis, principally aldosterone. Aldosterone’s synthesis is regulated mainly by the renin-angiotensin-aldosterone system and potassium levels, not significantly by ACTH (adrenocorticotropic hormone). Aldosterone regulates electrolyte balance by promoting sodium reabsorption and potassium excretion in the kidneys.
• Zona Fasciculata (ZF):
  • Location: The broad middle layer, constituting about 65-80% of the cortex’s volume.
  • Cell Arrangement: Cells are arranged in long, straight cords, typically one or two cells thick, running perpendicular to the gland surface and separated by sinusoidal capillaries. This “fascicle” or bundle arrangement gives it its name.
  • Cell Morphology: Cells are larger and more polyhedral than those in the zona glomerulosa. Their cytoplasm is characteristically pale and vacuolated due to a high content of lipid droplets (cholesterol esters and fatty acids), which are precursors for steroid synthesis. In H&E sections, these lipid droplets are often dissolved during processing, leaving the cytoplasm with a clear or “spongy” appearance, leading to the term “spongiocytes” for these cells. They possess abundant SER and mitochondria.
  • Function: The principal site of glucocorticoid synthesis, primarily cortisol. It also produces small amounts of androgens. Cortisol synthesis is regulated by ACTH from the pituitary gland. Glucocorticoids are essential for glucose metabolism, suppressing inflammation, and helping the body cope with stress.
• Zona Reticularis (ZR):
  • Location: The innermost layer of the cortex, adjacent to the medulla. It is the narrowest cortical zone.
  • Cell Arrangement: Cells are arranged in irregular, anastomosing cords that form a net-like (reticular) pattern, separated by capillaries.
  • Cell Morphology: Cells are generally smaller than those in the zona fasciculata. Their cytoplasm is often more eosinophilic than fasciculata cells and contains fewer lipid droplets. Lipofuscin pigment granules may be present, increasing with age. Cells show features of steroid synthesis but may appear more condensed or even degenerating towards the medulla.
  • Function: Primarily synthesizes androgens (like dehydroepiandrosterone, DHEA) and smaller amounts of glucocorticoids. Like the fasciculata, its activity is largely regulated by ACTH. Adrenal androgens contribute to secondary sex characteristics, particularly in females.

2.3. The Adrenal Medulla: Catecholamine Headquarters

The adrenal medulla is the inner, centrally located portion of the gland. It is essentially a modified sympathetic ganglion.

• Location: The core of the adrenal gland, surrounded by the cortex.
• Cell Type: The main cell type is the chromaffin cell. These cells are derived from neural crest cells, similar to postganglionic sympathetic neurons, but they lack axons and dendrites and instead secrete their products into the bloodstream.
  • Morphology: Chromaffin cells are relatively large, polyhedral cells, typically arranged in cords or clumps around capillaries and venules. Their cytoplasm stains basophilic in H&E. A defining characteristic is their affinity for chromium salts (used in some fixatives), which oxidize catecholamines into brown pigments, hence the name “chromaffin” (affinity for chromium). Ultrastructurally, they contain numerous dense-core secretory granules.
  • Function: Chromaffin cells synthesize and secrete catecholamines, primarily epinephrine (adrenaline) and norepinephrine (noradrenaline), directly into the bloodstream. Epinephrine is the predominant hormone, constituting about 80% of the secretion. These hormones are released in response to sympathetic nervous system stimulation (e.g., stress, fear, exercise) and mediate the “fight-or-flight” response, affecting heart rate, blood pressure, metabolism, and blood flow distribution.
• Other Features: The adrenal medulla contains a rich network of capillaries and venous sinusoids. Some scattered sympathetic ganglion cells may also be present. It receives direct innervation from preganglionic sympathetic fibers.

In summary, the adrenal gland presents a clear zonation in its cortex (glomerulosa, fasciculata, reticularis) producing distinct steroid hormones, surrounding a medulla composed of chromaffin cells secreting catecholamines, all within a connective tissue capsule.

3. The Pancreas: A Dual-Function Organ

The pancreas is an elongated gland located posterior to the stomach. It is unique in that it serves as both an exocrine gland, producing digestive enzymes, and an endocrine gland, producing hormones that regulate blood glucose.

3.1. Overall Microscopic Structure

The pancreas is covered by a thin connective tissue capsule, from which septa extend into the gland, imperfectly dividing it into lobules. Within these lobules lie the functional components: the vast majority consists of the exocrine pancreas, while scattered within this tissue are the lighter-staining clusters of the endocrine pancreas, known as the Islets of Langerhans.

3.2. The Exocrine Pancreas: Digestive Enzyme Factory

The exocrine component constitutes the bulk (about 80-85%) of the pancreatic tissue.

• Structure: It is composed of numerous acini, which are spherical clusters of secretory cells surrounding a small central lumen. These are classic serous acini.
• Acinar Cells:
  • Morphology: Acinar cells are pyramidal or wedge-shaped, with their apex facing the central lumen and their base resting on a basal lamina. They exhibit distinct polarity.
    • Basal region: Basophilic staining due to the abundant rough endoplasmic reticulum (RER) involved in protein synthesis. The nucleus is typically round and located basally.
    • Apical region: Acidophilic (eosinophilic) due to the presence of numerous large, membrane-bound secretory granules called zymogen granules. These granules contain inactive precursors of digestive enzymes (e.g., trypsinogen, chymotrypsinogen, amylase, lipase).
  • Function: Synthesize, store, and secrete a wide array of digestive enzymes into the pancreatic duct system. This secretion is stimulated primarily by cholecystokinin (CCK) and acetylcholine.
• Duct System: The acinar lumens drain into a system of ducts.
  • Centroacinar Cells: Unique to the pancreas, these are pale-staining, flattened cells that form the beginning of the duct system within the lumen of the acinus itself. They are the initial cells of the intercalated ducts.
  • Intercalated Ducts: Small ducts lined by low cuboidal epithelium, receiving secretions from the acini (including contributions from centroacinar cells, which secrete bicarbonate and fluid).
  • Intralobular Ducts: Formed by the convergence of intercalated ducts, still within the lobule, lined by cuboidal epithelium.
  • Interlobular Ducts: Larger ducts located in the connective tissue septa between lobules, lined by columnar epithelium.
  • Main Pancreatic Duct (Duct of Wirsung) and Accessory Duct (Duct of Santorini): These large ducts collect secretions from the interlobular ducts and empty into the duodenum. They are lined by tall columnar epithelium, often with scattered goblet cells. Duct cells in general contribute bicarbonate-rich fluid, stimulated by secretin, which helps neutralize acidic chyme entering the duodenum.

3.3. The Endocrine Pancreas: The Islets of Langerhans

The endocrine component consists of clusters of endocrine cells known as the Islets of Langerhans.

• Structure: Islets are spherical or oval clusters of cells, typically 100-200 µm in diameter, scattered throughout the exocrine tissue. They stain more lightly in H&E than the surrounding acini, giving them a pale appearance under the microscope. They are richly vascularized by fenestrated capillaries.
• Cell Types: Islets are composed of several types of endocrine cells, distinguished by their location within the islet and the hormones they produce. Specialized immunostaining techniques are required to definitively identify each type, but some general patterns exist:
  • Beta Cells (B cells): The most numerous type (about 70-80% of islet cells). They are typically located in the central core of the islet. They produce and secrete insulin, the primary hormone that lowers blood glucose levels. Betal cells stain less densely with H&E.
  • Alpha Cells (A cells): Make up about 15-20% of islet cells and are usually located in the periphery of the islet. They produce and secrete glucagon, which raises blood glucose levels.
  • Delta Cells (D cells): Relatively scarce (5-10%). They are scattered throughout the islet. They produce and secrete somatostatin, a hormone that inhibits the release of insulin, glucagon, and other gastrointestinal hormones.
  • PP Cells (F cells): Also scarce (about 1%) and more common in the head of the pancreas. They produce pancreatic polypeptide, which helps regulate pancreatic exocrine secretions and appetite.
• Function: The hormones secreted by the islet cells are released directly into the bloodstream, playing a critical role in regulating carbohydrate, fat, and protein metabolism, with insulin and glucagon being the primary regulators of blood glucose homeostasis.

In summary, the pancreas reveals a striking arrangement: the majority of the tissue is composed of enzyme-secreting serous acini and their associated duct system (exocrine function), with scattered, lighter-staining clusters, the Islets of Langerhans, containing specialized cells that secrete hormones (endocrine function).

Conclusion

Microscopic examination of the parathyroid glands, adrenal glands, and pancreas reveals highly specialized structures and cell types, each uniquely adapted to perform critical endocrine and/or exocrine functions. The parathyroid glands, with their chief and oxyphil cells, precisely regulate calcium. The adrenal glands, with their distinctly zoned cortex and medulla, manage stress responses, metabolism, and electrolyte balance through steroid and catecholamine production. The pancreas ingeniously combines vast exocrine acinar tissue for digestion with scattered endocrine islets for metabolic regulation. Understanding these microscopic details is essential for appreciating the complex physiology and potential pathology of these vital organs.