Lesson 25 - Endocrine System II (Notes) PDF

Cytology and Histology _____________ LESSON 25 ______________ ENDOCRINE SYSTEM (II) I. THYROID GLAND The thyroid is an endocrine gland located in the dorsolateral area of the trachea, at the level of the larynx. It is made up of 2 lobes surrounded by a capsule of loose connective tissue rich in re...

Cytology and Histology _____________ LESSON 25 ______________ ENDOCRINE SYSTEM (II) I. THYROID GLAND The thyroid is an endocrine gland located in the dorsolateral area of the trachea, at the level of the larynx. It is made up of 2 lobes surrounded by a capsule of loose connective tissue rich in reticulin fibres that emits thin trabeculae that, in turn, divide each lobe into irregular lobules. It is derived from the endoderm of the ground of the embryonic pharynx, and is shaped like a butterfly, with two lobes joined by the isthmus at its posterior pole. It is a follicular endocrine gland that has two types of cells that, in turn, produce two different types of hormones: 1) Follicular cells make up 90% of the glandular parenchyma and produce the thyroid hormones T3 (tri-iodothyronine) and T4 (thyroxine or tetra-iodothyronine), which are derived from amino acids and regulate the body's basal metabolism. 2) Parafollicular cells make up 10% of the glandular parenchyma and produce calcitonin, a protein hormone that regulates calcium metabolism (Figure 1). A B Figure 1.- Follicular cells forming thyroid follicles (A) and parafollicular cells forming cords (B). HE staining in (A) and calcitonin in (B). Follicular cells form a simple cuboidal or columnar epithelium that surrounds a central cavity and rests on a basement membrane around which a network of basket capillaries is arranged. This structure is called the thyroid follicle and is the morphological unit of the thyroid parenchyma. This hollow sphere contains a macroscopically gelatinous and microscopically eosinophilic substance that is homogeneous in sections stained with haematoxylin-eosin and is called colloid (Figure 1). The colloid is glycoprotein in nature and is called iodized thyroglobulin, which is the storage form of the thyroid hormones T3 and T4. Production of thyroid hormones (Figure 2): • Synthesis and storage phase: Thyroglobulin is synthesized by the rough endoplasmic reticulum and the Golgi complex and secreted by exocytosis to the colloid in response to stimulation of follicular cells by pituitary TSH. Follicular cells also produce and secrete thyroid peroxidase to the colloid, and take iodine through the basement membrane, transporting it to the colloid. Thyroid peroxidase produces the oxidation of iodine and its combination with thyroglobulin in the colloid, where it is stored. • Mobilization and passage to blood: Pituitary TSH also induces the formation of pseudopods on the surface of follicular cells, which capture iodine thyroglobulin Cytology and Histology through endocytosis, fusing with lysosomes to form heterolysosomes, in which iodinated thyroglobulin undergoes proteolysis to give rise to thyroxine (T4) and tri-iodothyronine (T3). These two hormones are secreted by diffusion along the basal border of the follicular cells and reach the basket capillaries surrounding the thyroid follicle. Figure 2.- Thyroid hormone production scheme (Häggström, M., 2014.Medical gallery.WikiJournal of Medicine 1 (2)) The size of the thyroid follicles and the morphology of the follicular cells vary with their functional status: • Synthesis follicle (active follicles): The follicles are medium in size (0.5 millimetres), with pale colloid and homogeneous surface and columnar cells with the nucleus at the basal pole surrounded by abundant rough endoplasmic reticulum and numerous mitochondria. Above the nucleus, a well-developed Golgi complex is located, and at the apical pole are numerous small, mediumdensity secretory granules containing thyroglobulin, the glycoprotein synthesized by follicular epithelial cells. The apical surface of the cells presents microvilli. • Resting follicle (inactive follicles): The follicles are large (0.9 to 1.0 millimetres), they contain abundant dark and homogeneous colloid that reaches the apical border of the follicular cells, and the follicular epithelial cells are cuboidal or even squamous and contain few organoids in their cytoplasm. • Secretion follicles (intermediate follicles): The follicles are small in size (0.2 to 0.5 millimetres) and the colloid presents numerous clear vacuoles next to the apical surface of the follicular cells, which are cuboidal in morphology and present endocytosis vesicles, lysosomes and phagolysosomes which are located in the apical portion of the cytoplasm and are electrodense. Between the follicular epithelial cells, near their apical border, there are numerous modes of attachment. Parafollicular cells or C cells are derived from the neural crest and are arranged singly or in small groups between the follicular cells and the basement membrane (Figure 1). Their cytoplasm is pale and contains a highly developed RER and Golgi complex, as well as numerous small secretion granules, of moderate to high electron density, distributed throughout the cytoplasm, in which calcitonin accumulates (Figure 1). This hormone is synthesized in response to high levels of calcium in the blood, inducing its decrease by reducing the reabsorption of calcium from bone tissue. II. PARATHYROID GLAND The parathyroid glands (two or more than two) can be found inside or outside the thyroid. If they are outside, they can travel from the thyroid area to the entrance of the Cytology and Histology thoracic cavity along the trachea, and then they are surrounded by a thin capsule of loose connective tissue. If they are inside, they are surrounded by the thyroid stroma (Figure 3). They are highly vascularized with numerous capillaries and sinusoids between which the parenchymal cells are arranged in small irregular cords or small nests. In all species, they present parenchymal cells called chief or principal cells that produce parathormone (Figure 1) (hypercalcemic), while in horses and ruminants they also present a second type of parenchymal cells called oxyphil or oxyphilic cells. A A Figure 3.- Thyroid (left) and parathyroid (right) glands (A), HE, 4X. Parathyroid cell under electron microscope (B). The chief or principal cells are the most numerous, they have a spherical nucleus and a variable cytoplasm with their functional state. The inactive cells have a poorly stained cytoplasm, with few organelles and few secretory granules which are more numerous in the active chief cells. The active chief cells also present a slightly basophilic cytoplasm with abundant rough endoplasmic reticulum and a welldeveloped Golgi complex, as well as numerous mitochondria and secretory vesicles (Figure 1). Chief cells produce parathormone in response to low calcium serum levels; this hormone increases calcium levels by increasing its reabsorption from bone tissue, decreasing its excretion at the renal level and stimulating its absorption at the intestinal level. Oxyphil cells are scarcer and larger than chief cells. In the horse and ruminants they can be isolated or in small groups, being very scarce in the rest of the domestic mammals. These cells contain little rough endoplasmic reticulum, small Golgi complex, few secretory granules, but numerous mitochondria. Its role is unclear. III. ADRENAL GLANDS The adrenal glands are two glands that are located in the perirenal adipose tissue retroperitoneally, near the cranial pole of both kidneys. They have very variable size and morphology in the different animal species, although they are usually elongated, measuring between 1-1.5 cm of length. The parenchyma is clearly divided into a cortex, which represents 70-80% of the volume of the gland, is brownish-reddish in colour and of mesodermal origin, and a medulla, which represents approximately 2030% of the volume of the gland, with a greyish colouration and neuroectodermal origin. The stroma is made up of a thin capsule of dense connective tissue that occasionally emits fine trabeculae that penetrate the cortex, but do not usually reach the medulla. In the capsule it is common to observe small groups of undifferentiated cells, similar to those of the cortex, and which are reserve cells that undergo proliferation and differentiation processes throughout the life of the animal. The cortex is located on the periphery of the gland, being divided into 3 zones that, from outside to inside, are: the glomerular zone, the fascicular zone and the reticular zone (Figure 4). • The glomerular zone or zona glomerulosa (Figure 4; Figure 5) is made up of irregular cords of cells interspersed with capillaries (hence the name glomerular) Cytology and Histology in ruminants, while in the rest of the species the cells form arches whose convex portion is oriented towards outside and separated from each other by little connective tissue. Due to this morphology, it is also called the arcuate zone. The cells of the glomerular zone have a columnar morphology, of variable height, with a spherical or ovoid basophilic nucleus in a central position, and a homogeneous cytoplasm. At the ultrastructural level, these cells present abundant SER, mitochondria with tubular crestae, multilocular Golgi complex, scant RER, and some lipid vacuoles scattered in the cytoplasm. Therefore, its ultrastructural characteristics correspond to those of steroid-producing cells. Figure 4.- Diagram of the adrenal gland cortex (Gl, glomerular zone; Fa, fascicular zone; Re, reticular zone). • • The fascicular zone or zona fasciculata (Figure 4; Figure 5) is a continuation of the glomerular zone into the adrenal gland and is the largest of the three cortical layers. It is made up of single-layer cords of cuboidal or slightly columnar cells that are arranged parallel to each other and radially and between which there is little reticular connective tissue with abundant capillaries. The cells have characteristics similar to those of the glomerular zone, but the cytoplasm is more vacuolized and for this reason they are called spongiocytes. At the ultrastructural level, these cells are similar to those of the glomerular zone, but with a larger cytoplasm and a greater amount of SER and RER, tubular mitochondria, numerous electron lucent lipid vacuoles, greater quantity of electron dense lysosomes and lipofuscin pigment, as well as a greater number of communicating junctions. The reticular zone or zona reticularis (Figure 4; Figure 5) is made up of anastomosed cords, oriented in different directions, of polyhedral cells with morphological characteristics similar to those of the fascicular zone, but which are somehow smaller, with less vacuolized cytoplasm and a more pyknotic nucleus. With electron microscopy, a greater amount of heterochromatin is observed at the nucleus level, while the cytoplasm has fewer lipid vacuoles, less SER and mitochondria and a smaller Golgi complex, while they show a greater amount of lipofuscin pigment than cells of the fascicular zone. These changes in the innermost cells of the reticular zone indicate that they undergo degenerative processes. A B C Figure 5.- Cells of the glomerular zone (A), fascicular zone (B) and reticular zone (C) of the adrenal cortex. Cytology and Histology Histiophysiology of the adrenal cortex The adrenal cortex is essential for life. It produces three large groups of hormones, mineralocorticoids, glucocorticoids, and sex hormones. They are steroid hormones, (they are synthesized from cholesterol) that are stored in intracytoplasmic lipid vacuoles. (1) The main mineralocorticoid produced by the glomerular zone of the adrenal cortex is aldosterone, which acts on the distal convoluted tubules of the kidney increasing tubular reabsorption of sodium. As a consequence, tubular secretion of potassium and hydrogen ions increases, and water retention occurs. Therefore, aldosterone helps regulate blood volume and electrolyte balance. Aldosterone secretion is independent of ACTH. The release of this hormone occurs when there is a decrease in the concentration of sodium or an increase in the concentration of potassium in the blood through the action of the renin-angiotensin system. (2) Glucocorticoids are produced in the fascicular zone, the main one being cortisol, followed by cortisone and corticosterone. Glucocorticoids regulate the metabolism of carbohydrates, proteins, and fats. Thus, cortisol is hyperglycemic and reduces the peripheral use of glucose (it is, therefore, diabetogenic), decreases protein synthesis at all levels except at the liver level, and is lipolytic in adipose tissue. In addition, it has anti-inflammatory and anti-allergic effects, which is why it is widely used in veterinary medicine. The synthesis and release of glucocorticoids is regulated by the pituitary through its blood levels and corticotropic hormone (ACTH). (3) Lastly, the normal adrenal cortex also produces small amounts of androgens, oestrogens, and progesterone at the level of the reticular zone, both in males and females. The adrenal medulla (Figure 6) is arranged in the central portion of the gland, it is smaller than the cortex and the transition between the two is usually irregular, with cortical cell cords penetrating the medulla. The adrenal medulla is made up of 2 types of cells: glandular cells and ganglion cells. • The glandular or chromaffin cells form irregular groups, have polyhedral morphology, are large, and are polarized (on one side a capillary and on the other side, a venule). They have a very basophilic cytoplasm with granules that stain brown with chromium salts, and that is why they are called chromaffin cells and belong to the APUD system of endocrine cells. Cytoplasmic granules contain catecholamines. With immunohistochemical techniques, two types of glandular cells can be differentiated in the adrenal medulla: a) Norepinephrine (noradrenaline) producing cells: Under electron microscopy, these cells contain large, spherical nuclei, numerous secretory granules with an electrodense nucleus, abundant RER, mitochondria, and Golgi complex. b) Cells that produce epinephrine (adrenaline): They are larger than the previous ones and the secretory granules are of lower electron density and more homogeneous. • Sympathetic ganglion cells are found, singly or in groups, between the strands of chromaffin cells. Histiophysiology of the adrenal medulla The activity of the adrenal medulla is regulated by the hypothalamus through sympathetic endings of the splanchnic nerves, which upon receiving stimuli release acetylcholine, which stimulates the chromaffin cells of the adrenal medulla, which secrete adrenaline and norepinephrine to capillaries, increasing abruptly (up to 300 times) the plasma concentration of adrenaline, which increases the heart rate and tissue irrigation, and the release of glucose, among other actions, while norepinephrine increases blood pressure. These two catecholamines are produced in situations of stress, alertness, or sudden emotional changes and are rapidly degraded. The adrenal glands are one of the most irrigated organs in the body, with numerous arteries that penetrate the capsule, branch through the trabeculae and give rise to numerous sinusoid capillaries that are located between the cords of cells both Cytology and Histology at the level of the cortex and the medulla. These sinusoid capillaries lead to postcapillary venules communicating with larger venules. Figure 6.- Diagram of the adrenal medulla.