Microanatomy of Endocrine Glands II (PDF)

Microanatomy of Endocrine Glands II Dr. Avril Genene Holt Page 1 of 22 MICROANATOMY OF ENDOCRINE GLANDS II Learning Objectives: 1. Describe the microanatomy and functions of the pineal gland (epiphysis)....

Microanatomy of Endocrine Glands II Dr. Avril Genene Holt Page 1 of 22 MICROANATOMY OF ENDOCRINE GLANDS II Learning Objectives: 1. Describe the microanatomy and functions of the pineal gland (epiphysis). Describe the anatomical appearance, location, and histological organization of the pineal gland. Describe the cell types in the pineal gland and their function. Describe the histological diagnostic feature of the pineal gland. Compare and contrast the features of the pineal gland with those of other endocrine glands. 2. Describe the microanatomy and functions of the thyroid gland. Describe the anatomical appearance, location, and histological organization of the thyroid gland. Describe the cell types in the thyroid gland and their function. Describe thyroid follicles: a. cells making up the epithelium, b. content of the lumina, c. relationship with the vasculature and d. histological staining characteristics in LM (H&E, PAS). Describe the process of thyroglobulin synthesis by follicular cells and the reuptake and processing of thyroglobulin into its component products as well as their role and/or fate. Describe the location and appearance of parafollicular ("C cells") cells in LM and TEM. Describe the function of parafollicular cells and the mechanism controlling secretion. 3. Describe the microanatomy and functions of the parathyroid gland. Describe the anatomical appearance, location, and histological organization of the parathyroid gland. Describe the cell types in the parathyroid gland and their function. Describe age-related changes in the parathyroid gland. Describe the mechanism controlling secretion of the glandular products in the parathyroid gland. 4. Describe the microanatomy and functions of the adrenal (suprarenal) gland. Describe the histological organization of the adrenal cortex. Compare and contrast the organization and products of the subdivisions of the adrenal cortex. Describe the course of blood vessels and blood flow within the adrenal gland. Describe the histological organization of the adrenal medulla. Describe the cell types and products within the adrenal medulla. Describe the control mechanism for hormone secretion within the adrenal medulla. Microanatomy of Endocrine Glands II Dr. Avril Genene Holt Page 2 of 22 Lecture Content Outline: I. Introduction to endocrine system - Overview II. Pineal Gland A. Relationships and Development B. Contents C. Functions III. Thyroid Gland A. Structure B. Blood Supply C. Cell Types IV. Parathyroid Glands A. Morphology B. Cell Types C. Function V. Adrenal Glands (Suprarenal Glands) A. Relationships B. Blood Supply C. Adrenal Cortex D. Adrenal Medulla I. Introduction to Endocrine System (Review) The endocrine system produces a variety of secretions called hormones that influence numerous other cells and organ systems. The hormones are typically carried through Figure 1. Endocrine glands release hormones that influence cells and organ systems. The hormones the vasculature to a distant site but may also can go into the blood and act at a distant site in true endocrine fashion (a). They can act on diffuse and function locally in a paracrine neighboring cells in a paracrine fashion (b). They manner (Figure 1). can even act on the same cells that produce them, which is called an autocrine effect (c). Figure 21.1 in Ross and Pawlina, 6th ed., 2011. Hormones include three classes of compounds: (1) Peptides, proteins, and glycoproteins. These substances are produced within the rough endoplasmic reticulum, packaged in the Golgi complex, stored in secretory vesicles, and released at the cell surface. Microanatomy of Endocrine Glands II Dr. Avril Genene Holt Page 3 of 22 (2) Steroids. These compounds are produced by the cooperative action of enzymes located in smooth endoplasmic reticulum and mitochondria on substrates found in lipid droplets. Their transport in the blood stream requires binding to plasma proteins or specialized carriers. (3) Amino acid analogues and derivatives, including catecholamines. In general, protein hormones act on cell surface receptors and exert their physiological effects through second messenger systems whereas steroid hormones enter the target cell and bind to their DNA, causing the production of new proteins and hormone- specific responses. The organization of endocrine organs facilitates the release of their products into blood vessels. These organs have no duct system. Instead, they usually appear as clumps or cords of cells, surrounded by a dense plexus of fenestrated capillaries. The hypophysis (pituitary gland) was covered in an earlier lecture. This lecture will include the pineal, thyroid, parathyroid and adrenal glands. Other endocrine organs include the endocrine pancreas which was discussed in the GI Renal course. There are endocrine components in the ovary and testis as well as a diffuse system of endocrine cells within the lining of the respiratory system and the gastrointestinal system. Each of these other endocrine elements have been discussed in earlier lectures. Microanatomy of Endocrine Glands II Dr. Avril Genene Holt Page 4 of 22 I. Pineal Gland (Epiphysis cerebri) (Figure 2) A. Relationships and Development 1. Dorsal extension from the posterior part of the roof of the diencephalon. 2. Lumen is obliterated as walls thicken with age. Figure 2. Section through pineal gland (H&E). 3. Remains attached to the roof of the third ventricle. 4. Covered by a capsule that is continuous with the pia mater and extends into the gland as septae and trabeculae, separating the parenchyma into clumps of cells (lobules) (Figure 3, top). B. Contents (Figure 3) 1. Pinealocytes a. Major cell type (95%). Figure 3. Top: Section through the pineal gland (H&E). The very thin capsule at the top of the b. Relatively large cells section (Cap) sends connective tissue (CT) trabeculae down into the gland, dividing the with deeply creased parenchyma into small clumps of cells or lobules (L). Bottom: Higher magnification view of (crenated) nuclei, parenchyma in pineal gland, showing presence of corpora arenacea or brain sand (BS). Most of the prominent nucleoli, nuclei belong to pinealocytes. Inset: High magnification view showing glial cells (G) and long cytoplasmic around a piece of brain sand (BS). Most of the processes with club- other nuclei belong to pinealocytes. Some fibroblasts are also visible in the upper right. A: shaped terminations. artery, C: capillary, V: vein. Plate 82.2 from Chapter 21 in Ross and Pawlina, 7th ed, 2016. Microanatomy of Endocrine Glands II Dr. Avril Genene Holt Page 5 of 22 2. Glial cells a. Less numerous than pinealocytes (5%). b. Cells have long cytoplasmic processes that form a supporting network associated with blood capillaries. They may have neuroendocrine activity. 3. Corpora arenacea, brain sand, or acervuli (Figure 3) a. Concretions of calcium phosphate salts located in areas of glia and stroma. b. Number and size increase with age. c. Corpora arenacea make the pineal a useful radiological landmark in computerized tomography (CT) scans. C. Functions 1. Pinealocytes synthesize serotonin, melatonin, and a number of specific peptides (e.g., neurohormones). 2. Hormones may play a role in regulating gonadal function, since tumors that destroy the pineal are associated with early-onset puberty. 3. Role in adjusting to sudden changes of day length (jet lag) and in seasonal affective disorder (SAD). Microanatomy of Endocrine Glands II Dr. Avril Genene Holt Page 6 of 22 II. Thyroid Gland A. Structure (Figures 15 and 16) 1. Two lateral lobes, connected by an isthmus, that cross the midline at the level of the larynx/upper trachea. Occasionally a pyramidal lobe extends up from the isthmus. Weight about 40 grams. 2. Connective tissue stroma. A delicate connective tissue covering forms a thin capsule extending into Figure 4. Structure and location of the thyroid gland. Plate 76 in Netter, 2014. and subdividing the gland into lobules. 3. Follicular organization a. Gland arranged into spherical follicles ranging in size up to 1 mm in diameter Figure 5. Light micrograph of thyroid gland (H&E). (Figures 5 and 6). Microanatomy of Endocrine Glands II Dr. Avril Genene Holt Page 7 of 22 b. Lumen of follicles is filled with colloid, the stored secretory product of the follicular cells, iodinated thyroglobulin (Figures 6 and 7). Figure 6. Light micrograph of thyroid gland (H&E), showing the spherical arrangement of c. Follicles are lined with thyroid parenchymal cells and the presence of colloid within the follicle lumen. Slide F9-D2 a simple cuboidal from Erlandsen and Magney (1985). epithelium resting on a basement membrane (Figure 7). B. Blood Supply 1. Mostly from superior and inferior thyroid arteries. Figure 7. Light micrograph of a group of thyroid follicles (H&E). Note the simple cuboidal 2. The arteries deliver blood to epithelium lining the follicles. The follicle lumens a dense network of fenestrated contain colloid (iodinated thyroglobulin). Slide F9-D6 from Erlandsen and Magney (1985). capillaries that surrounds each follicle (Figure 8). 3. Veins in gland form a rich plexus. 4. Good lymphatic drainage. Figure 8. SEM of a vascular cast of the thyroid gland. Note the tortuous arrangement of fenestrated capillaries around the follicles. The basket-like arrangement of capillaries is indicative of the high vascularity of the thyroid gland. Slide F9-D5 from Erlandsen and Magney (1985). Microanatomy of Endocrine Glands II Dr. Avril Genene Holt Page 8 of 22 C. Cell Types 1. Thyroid follicular cells (Figure 9) a. Simple cuboidal epithelium is typical, may vary in height with activity. b. Epithelium rests on a thin basement membrane, surrounded by fenestrated Figure 9. TEM of follicular cells lining a thyroid capillaries. follicle. The follicle lumen containing colloid is at the top of the image. Part of a fenestrated capillary is at the bottom. CRD: colloid resorption droplets, EBL: basal lamina of c. Produce thyroxin (T4) fenestrated capillary endothelial cell, En: cytoplasm of fenestrated capillary endothelial and triiodothyronine cell, FBL: basal lamina of follicular cell, G: Golgi apparatus, JC: junctional complex, L: lipid (T3). droplet, Mv: microvilli, N: nucleus, rER: rough enoplasmic reticulum, Figure 21.15 in Ross and Pawlina, 7th ed., 2016. d. These are the only endocrine cells that provide for extracellular storage of secretory product. e. Mechanism of thyroid hormone production (Figure 10). i. Follicular cells concentrate I- at least 30-fold from the blood by means of ATP-dependent iodide transporters. ii. Rough ER synthesizes thyroglobulin Microanatomy of Endocrine Glands II Dr. Avril Genene Holt Page 9 of 22 polypeptides, adds mannose and glucosamine. Figure 10. Diagram of steps in thyroid hormone synthesis. Figure 21.17 in Ross and Pawlina, 7th ed., 2016. iii. Golgi condenses this protein, adds galactose, fucose and mannose. iv. Thyroglobulin is released by exocytosis into the follicle lumen. v. Follicular cells also produce thyroid peroxidase, which is packaged in the same vesicles as thyroglobulin polypeptide. vi. Thyroid peroxidase is inserted into the apical membrane and participates in the Microanatomy of Endocrine Glands II Dr. Avril Genene Holt Page 10 of 22 oxidation of iodide to free iodine and in the iodination of thyroglobulin. vii. Iodine is coupled to tyrosine groups in thyroglobulin, forming mono- and diiodothyronine (MIT and DIT) Coupling of two DIT yields T4; one MIT and one DIT yield T3. viii. Iodinated thyroglobulin (colloid) is stored in the follicle lumen and is then taken into follicular cells by endocytosis. ix. Colloid is hydrolyzed by lysosomal enzymes. T3 and T4 are released into the blood for transport by serum carrier proteins; MIT and DIT forms are recycled. x. All stages of T3 and T4 synthesis are controlled by TSH; feedback control by the hormones regulates synthesis and release of TRH. xi. T4 and T3 are produced in a 20:1 ratio by the thyroid. T3 is 5 times more active and is generated from T4 in kidney, liver, and heart. xii. T3 and T4 act to regulate tissue basal metabolism of carbohydrates, proteins, and fats; heat production; body and tissue Microanatomy of Endocrine Glands II Dr. Avril Genene Holt Page 11 of 22 growth and development. 2. Parafollicular Cells a. Large cells that stain poorly with H&E. b. Parafollicular cells can be found in two locations. i. Within wall Figure 11. Light micrograph of thyroid gland stained for the hormone calcitonin. Cells that are of follicle stained dark brown contain calcitonin. These parafollicular cells are located in the wall of the beneath thyroid follicle underneath the follicular cells. follicular Slide F9-D8 from Erlandsen and Magney (1985). cells (Figure 11): When included within the basement membrane of the follicle, they do not contact the lumen. ii. In small clusters within the interstitium (connective tissue) between follicles. Microanatomy of Endocrine Glands II Dr. Avril Genene Holt Page 12 of 22 c. Contain secretory granules in close proximity to surrounding capillaries (Figure 12). d. Produce calcitonin Figure 12. Right: TEM of parafollicular cell in (thyrocalcitonin). the wall of a thyroid follicle. A follicular cell is to i. Depresses the right, and a fenestrated capillary is in the lower left corner. Note that the secretory osteoclast granules are accumulated in the cytoplasm near the capillary. Left: Blow-up of boxed region in activity, i.e., it image on the right, showing calcitonin secretory granules. Figure 21-6 and 21-7 in Rhodin, 1974. stops release of Ca++ from bone breakdown. ii. Increases renal and intestinal Ca++ excretion. iii. The result of both of these actions is lowered blood calcium. IV. Parathyroid Glands A. Morphology Microanatomy of Endocrine Glands II Dr. Avril Genene Holt Page 13 of 22 1. Two glands about the shape and size of a pea are associated with the dorsal surface of each lobe of the thyroid gland. 2. Surrounded by very delicate connective tissue (CT) capsule extending incomplete trabeculae into the gland (Figure 13). 3. Essential for life. Figure 13. Light micrograph of parathyroid gland (H&E). 4. Fat cells and connective tissue (CT) increase with age. 5. Cells arranged in clumps within a rich vascular network. 6. Two cell types (Figures 14 and 15) a. Principal or chief cells i. Relatively small cells with large nuclei and a few small secretory granules. ii. Produce hormone parathyroid hormone (parathormone - PTH) Microanatomy of Endocrine Glands II Dr. Avril Genene Holt Page 14 of 22 Figure 14. Light micrograph of parathyroid gland Figure 15. TEM of parenchyma in parathyroid parenchyma (H&E), showing the presence of gland, showing principal or chief cells and an principal or chief cells and oxyphils (clump of oxyphil at right. 1: nuclei of chief cells, 2: eosinophilic cells at bottom center of field. Slide oxyphil cell crowded with mitochondria, 3: F9-E3 from Erlandsen and Magney (1985). glycogen, 4: lipid droplet, 5: mitochondria, 6: cell borders, 7: lumen of fenestrated capillary, 8: secretory granules. Figure 22-4 in Rhodin, 1974. b. Oxyphil cells i. Appear at 4-7 years and increase with age. ii. Larger, acidophilic cells with many mitochondria and small nuclei. They may derive from chief cells. iii. Function largely unknown, but show traces of PTH. B. Function 1. PTH action is opposite to calcitonin. 2. If blood calcium is low, PTH will: a. Stimulate release of Ca++ from bone by activating osteoclasts (Figure 16) b. Stimulate Ca++ resorption by kidney tubules and intestines. Microanatomy of Endocrine Glands II Dr. Avril Genene Holt Page 15 of 22 Figure 16. Diagram showing the role of PTH in the activation of osteoclasts to degrade bone and release Ca++. Note that PTH binds to an osteoblast, which then in turn drives the formation of an activated osteoclast. Modified from Figure 4-27 in Histology and Cell Biology (Kierszenbaum, 4th ed., 2016). V. Adrenal Glands (Suprarenal glands) A. Relationships 1. Crescent-shaped, paired organs, located at the cranial pole of each kidney. 2. Each gland consists of two separate endocrine organs: the adrenal cortex and the adrenal medulla (Figure 17). 3. Connective tissue stroma - Figure 17. Light micrograph of an adrenal gland a delicate CT in the (H&E). The outer region with three different regions of staining is the adrenal cortex and capsule and extending into consists of three zones. The cortex surrounds the innermost basophilic region, the adrenal medulla. the cortex as trabeculae; The large spaces are veins in the medulla. many reticular fibers. Microanatomy of Endocrine Glands II Dr. Avril Genene Holt Page 16 of 22 Figure 18. Diagram of structure and blood flow through the adrenal gland. Slide F9-E7 from Erlandsen and Magney (1985). B. Blood supply (Figure 18) 1. Arteries a. Capsular b. Cortical - give rise to capillaries in the cortex c. Medullary - arterioles ("medullary arterioles") course through the cortex and form capillary network in the medulla. 2. Veins a. There are no veins in the adrenal cortex. Microanatomy of Endocrine Glands II Dr. Avril Genene Holt Page 17 of 22 b. Venous return begins at the cortico-medullary junction where thin-walled cortical capillaries carrying hormone-rich but oxygen-poor blood from the cortex merge with the oxygen-rich blood of the medullary arterioles to form the thin-walled venous blood supply to the medulla. Figure 19. Light micrograph of the cortex of the adrenal gland. The 3 zones of the cortex stain differently. The outermost zone (top) is the zona glomerulosa (ZG), with basophilic staining. The middle zone, zona fasciculata (ZF) stains lightly staining. The innermost cortical layer, zona reticularis (ZR), stains darkly. A portion of the medulla is visible at the bottom of the image. Figure 20. Diagram illustrating the organization of the There is a thin connective tissue capsule just cells within the adrenal gland. Figure 21.21 in Ross and outside the zona glomerulosa. Pawlina, 6th ed., 2011. C. Adrenal cortex - three zones of glandular cells (Figures 19-21) 1. Zona glomerulosa (Figure 21) - outer zone (10-15%). a. Rounded clumps of cells, in close proximity to fenestrated capillaries. b. Dependent on angiotensin II. c. Produces aldosterone, a mineralocorticoid that increases sodium uptake in the kidney. Microanatomy of Endocrine Glands II Dr. Avril Genene Holt Page 18 of 22 d. Cytoplasm contains some lipid droplets and mitochondria with conventional cristae. e. Cells take up cholesterol by Figure 21. Light micrograph of the outer region of the adrenal cortex (H&E). The eosinophilic means of receptor- layer at the top is the thin connective tissue capsule of the adrenal gland. Just below that is mediated the zona glomerulosa that contains rounded clumps of cells. At the bottom of the image is the endocytosis of upper region of the zona fasciculata. LDLs, and making modifications through a series of hydroxylation reactions. During synthesis the developing hormone shuttles between the mitochondria and the smooth ER, which both contain synthetic enzymes. 2. Zona fasciculata (Figure 21) - middle zone (60-80%). a. Cells organized into straight cords or columns that run radially. b. Products are glucocorticoids, primarily cortisol, which function to promote metabolism and suppress inflammatory responses. This is an ACTH dependent zone. c. Cells contain numerous lipid droplets, mitochondria with tubulovesicular cristae, and an abundance of sER. These 3 components function together (Figure 22). Microanatomy of Endocrine Glands II Dr. Avril Genene Holt Page 19 of 22 Figure 22. TEM of zona fasciculata cell at high magnification. This cell is characterized by a large number of lipid droplets (unstained in this micrograph) and distinctive mitochondria which contain short tubulovesicular cristae, typical of those found in steroid-secreting endocrine cells. The cytoplasm also contains well developed smooth endoplasmic reticulum and occasional “thumb-print” patches of rough endoplasmic reticulum. These cells mainly secrete cortisol. Cells of the zona reticularis and most other steroid-secreting cells would look similar. Slide F9-F5 from Erlandsen and Magney (1985). 3. Zona reticularis (Figure 23) - inner zone (5-7%). a. Anastomosing network of smaller, darker cells. Fewer lipid droplets, more lipofuscin. b. Produces gonadocorticoids, mostly dehydroepiandrosterone; also some cortisol. This region is also ACTH dependent. Figure 24. Light micrograph showing the junction between the zona reticularis (left) and Figure 23. Light micrograph of the inner region the adrenal medulla (right). Note the cortical of the adrenal cortex (H&E). The pale-staining capillaries draining into the medullary capillaries. region at the top of the image is the lower portion The capillaries are carrying blood rich in cortical of the zona fasciculata. Just below that is the zona hormones into the medulla. Slide F9-F7 from reticularis that contains smaller, darker cells. Erlandsen and Magney (1985). D. Adrenal Medulla 1. Network of polyhedral cells surrounded by capillaries and Microanatomy of Endocrine Glands II Dr. Avril Genene Holt Page 20 of 22 cortical veins (Figure 24). 2. Cells are modified postganglionic sympathetic neurons. 3. Part of chromaffin system of cells that stain with dichromate salts. 4. Cells exhibit prominent Figure 25. TEM of the junction between the zona reticularis (left) and the adrenal medulla (right). Note Golgi complexes and the difference between the steroid-secreting cells of the zona reticularis and the protein-secreting cells of membrane-bound secretory the medulla. The zona reticularis cells contain lipid droplets (D), and many mitochondria, but no secretory granules containing granules, since they are steroid-secreting cells (see Figure 22). The epinephrine (Ep) and norepinephrine chromogranins that are (Nor) containing cells of the adrenal medulla are complexed with the characterized by the presence of many secretory granules. D: lipid droplet, Ep: epinephrine cell in catecholamines (Figure 25). medulla, N: nucleus of zona reticularis cells, Nor: norepinephrine cell in medulla, S: fenestrated capillary (sinusoid). Slide F9-F8 from Erlandsen and Magney (1985). 5. Separate cell populations produce epinephrine (80%) or norepinephrine (20%) (Figure 26). 6. Influence of cortex on medulla a. The cells that make epinephrine contain Figure 26. TEM of the adrenal medulla showing the the enzyme different granule types within norepinephrine- secreting (NE) and epinephrine-secreting (Ep) cells. phenylethanolamine Slide F9-G2 from Erlandsen and Magney (1985). N-methyltransferase (PNMT) that catalyzes synthesis of epinephrine from norepinephrine. The synthesis of PNMT is induced by glucocorticoids Microanatomy of Endocrine Glands II Dr. Avril Genene Holt Page 21 of 22 (in venous drainage from zona fasciculata). b. Glucocorticoids are also thought to suppress axon formation of adrenal medullary cells during development. 7. Note that the products of the adrenal cortex are not stored in vesicles, but the products of the adrenal medulla are stored in membrane-bound vesicles. Clinical Correlations Hypoadrenocorticism (Addison’s Disease) – Destruction of adrenal cortex (sometimes by tuberculosis) leads to weakness, weight loss, low blood pressure. Increased secretion of ACTH causes increased skin pigmentation. Hyperadrenocorticism (Cushing’s Syndrome) – Increased activity of adrenal cortex leading to obesity, hirsutism, “moon face”, thinning of skin and lipodystrophy. Pheochromocytomas – tumors of the adrenal medulla that lead to hypertension, elevated heart rate, anxiety, weight loss. Microanatomy of Endocrine Glands II Dr. Avril Genene Holt Page 22 of 22 References: Erlandsen, S.L. & Magney, J.E. Histology Microfiche Atlas, Univ. of Minnesota Press, Minneapolis, 1985 (fiche 9 & 12). Hammersen, F., (Sobotta/Hammersen) Histology A Color Atlas of Cytology, Histology, and Microscopic Anatomy, Urban & Schwarzenberg, Baltimore-Munich, 1980. [Cited in figures as “Sobotta”] Kessel, R.G. & Kardon, R.H. Tissues and Organs: A Text/Atlas of Scanning Electron Microscopy, W.H. Freeman & Co., San Francisco, 1979. Meyer, D. Unpublished Histology Slides, Wayne State University School of Medicine, 1972. Netter, F.H., Atlas of Human Anatomy (6th ed.), Saunders-Elsevier, Philadelphia, 2014, Chapter 1. Rhodin, J.A.G., Histology A Text and Atlas, Oxford University Press, New York, 1974, Chapter 32. Ross, M.H. & Pawlina, W., Histology (6th ed.), Lippincott, Williams & Wilkins, Baltimore, 2011, Chaps. 20 & 21. Ross, M.H. and Pawlina, W., Histology: A Text and Atlas, 6th ed., Lippincott Williams & Wilkins: Philadelphia, 2011, Ch. 21. Ross, M.H. and Pawlina, W., Histology: A Text and Atlas, 7th ed., Lippincott, Williams, & Wilkins, WoltersKluwer Health: Philadelphia, 2016, Ch. 21.