The+Endocrine+System+II+-+Thyroid,+Parathyroid,+Pancreatic+Islets,+and+Adrenals

=**Objectives**=


 * 1. Describe the histology of the thyroid gland.**

The thyroid consists of two lateral lobes connected by a narrow isthmus lying over the 2nd and 3rd trachial rings. It is embryological origin is from a down growth of the base of the tongue to the upper tracheal region, leaving a embryological remnant called the thyroglossal duct. The parenchyma of the thyroid is enclosed externally by a layer of dense irregular connective tissue. Beneath this outer connective tissue is a thin inner connective tissue capsule that penetrates the lobes of the gland, dividing it into lobules.

The functional units of the thyroid gland are spherical, cyst-like follicles. They consist of a simple cuboidal epithelium surrounding a colloid-filled space. The follicles vary in size and shape and are closely packed together. Look for a ring of epithelial cells around the pink-staining, homogenous colloid. The follicular cells (principal cell) are cuboidal and range from squamous to low columnar depending on their activity level. Active follicles are thought to have columnar cells while inactive follicles have squamous cells. The nucleus is spherical and has a vesicular chromatin pattern. The cytoplasm is faintly basophilic. The follicular cells secrete thyroglobulin, a glycoprotein, which is stored extracellularly in the colloid. The thyroglobulin is iodinated by thyroperoxidase produced by follicular cells and secreted into the lumen. Desmosomes and gap junctions seal off the border between follicular cells so that anything traveling form the colloid to the fenestrated capillaries must pass through the follicular cells. Thyroxin is absorbed from the colloid by follicular cells and released into the blood as thyroid hormone.

Parafollicular cells (light cells or “C” cells) are located in the connective tissue between follicles or adjacent to follicular cells within follicles. Sometimes the parafollicular cells are squeezed in between the follicular cells and occupy the same basement membrane but do not reach the lumen of the follicle because of the insulation from the thin cytoplasmic extensions (tight junctions) of the follicular cells. These cells are of neural crest origin and are slightly larger than the follicular cells and have a lighter staining cytoplasm. They secrete calcitonin, which lowers the calcium level in the blood.

The thyroid gland stroma consists of a thin layer of connective tissue and rich capillary network present between the follicles. Delicate septa subdivide the gland into poorly delineated lobules. The septa are continuous with the connective tissue capsule. This has a dense inner layer and an outer areolar layer.


 * 2. Describe the function of thyroid follicular cells and the synthesis, storage, and secretion of thyroid hormone.**

The thyroid follicular cell functions to synthesize and secrete thyroid hormone. Thyroglobulin is synthesised in the rER and packaged for secretion to the lumen; thyroperoxidase produced by the follicular cell and secreted into the lumen attaches iodine to thyroglobuin to produce iodinated thyroglobulin. When thyroid hormone is signaled for secretion by TSH, the iodinated thyroglobulin is taken up in colloid droplets on the apical surface and undergoes lysosomal digestion to produce T3 and T4 as well as mono-iodotyrosine and di-iodotyrosine. T3 and T4 are active forms of thyroid hormone; mono-iodotyrosine and di-iodotyrosine act as iodine carriers and are de-iodinated in the cytoplasm and reserved for recycling.


 * 3. Describe and identify the parafollicular (C-cells).**

Parafollicular cells are located in the connective tissue between follicles on the same basement membrane and are of neural crest origin, migrating into the thyroid during development. They are considerd part of the amine precursor uptake and decarboxylation (APUD) cell line. They are larger and lighter staining than follicular cells and have a spherical, centrally located nucleus. Parafollicular cells are located in the connective tissue between follicles or adjacent to follicular cells within follicles. Sometimes the parafollicular cells are squeezed in between the follicular cells and occupy the same basement membrane but do not reach the lumen of the follicle because of the insulation from the thin cytoplasmic extensions (tight junctions) of the follicular cells. They secrete calcitonin, which lowers the calcium level in the blood. Calcitonin is released in response to elevated plasma levels of Ca++ and inhibits ostioclast activity and promotes excretion of Ca++ from the kidney. Ca++ concentration is under the control of the Parathyroid gland.


 * 4. Describe and identify the histology of the parathyroid glands. Distinguish the chief (principle) cell from the oxyphil cells.**

Typically there are four parathyroid glands about the size of an apple seed attached to the dorsal surface of the thyroid gland with a pair of parathyroid masses located at each of the upper and lower portions of the thyroid lobes because of different embryologic origin. The inferior parathyroids are derived from the 3rd pharyngeal pouch and descended from thymus; the superior parathyroids are derived from the 4th pharyngeal pouch and descended from the thyroid. The connective tissue capsule of the parathyroid gland is continuous with the capsule of the thyroid gland. Delicate tissue septa extend into the parenchyma to divide the gland into poorly defined lobules. Finer septa divide the epithelial glandular cells into anastomosing cords or groups. Fat cells may help separate the groups of cells. Note the rich capillary network.

The parenchyma is composed of two types of cells: (1) principal or chief cells and (2) oxyphil cells. The principal cell is the most numerous and is polygonal in shape with a light staining cytoplasm. The chief cells secrete parathyroid hormone (PTH), which raises the blood calcium level. The target cell/organ of this hormone is osteoblasts in bones, distal convoluted tubules of the kidney, and small intestine, acting to stimulate osteoclast activity, Ca2+ resoprtion, and synthesis of 1,25-dihydroxycholecalciferol (a vitamin D derivative that facilitates calcium absorption from small intestine). PTH hormone secretion from chief cells is directly under control of plasma calcium concentrations. Oxyphil cells are scattered singly or in small clusters and have distinct cell boundaries. They are larger but less numerous than the chief cells and have an acidophilic cytoplasm due to numerous mitochondria. The function of oxyphil cells is unknown though they are not hormone secreting and possibly differentiated from chief cells.


 * 5. Describe the overall histology of the adrenal gland, its blood supply, and the embryological origin of each region.**

The adrenal glands consist of a pair of flattened, crescent-shapped glandular masses that lie on the superior-medial border of the kidneys. They consist of 2 concentric layers of tissue covered by thick fibroelastic connective tissue with rich vascular supply. The suprarenal gland is a composite organ consisting of two parts that are functionally, structurally and embryologically different: the outer cortex and inner medulla. The cortex is derived from mesoderm, the medulla from neural crest ectoderm. The adrenal gland receives blood from the superior adrenal artery (a branch from inferior phrenic artery), middle adrenal artery (a branch from the aorta) and inferior adrenal artery (a branch from the renal artery). These arteries branch in the outer capsule to form the capsular arteries. The capsular arteries penetrate the parenchyma of the gland where they branch extensively to form cortical and medullary arterioles. Cortical arterioles give rise to the capillary plexus of the cortex (zona glomerulosa) and the long cortical sinuses. The medullary arterioles form the capillary matrix of the medulla.


 * 6. Describe the three zones of the adrenal cortex, their constituent cells, and substances produced by the cells in each zone.**

The cortex is divided into three concentric zones: the zona glomerulosa, zona fasciculata and zona reticularis. Secretion of adrenocorticoids is controlled by the release of ACTH from basophils in the anterior pituitary and by the renin/angiotensin system.

The zona glomerulosa is thin and located immediately deep to the capsule; it is composed of small pyramidal or columnar cells located in spherical aggregates surrounded by capillaries. These cells have large deeply staining nuclei and homogenously staining cytoplasm. Zona glomerulosa cells secrete mineralcorticoid hormones aldosterone and deoxycorticosterone. Mineralocorticoids play a role in water an electrolyte homeostasis by promoting resorption of Na+ from the distal convoluted tubules of the kidney, sweat glands and salivary glands. Mineralocorticoids are controlled by the renin/angiotensin system but also to stress related release of ACTH.

The zona fasciculata makes up the majority of the cortex and is responsible for secreting the glucocorticoids, particularly the hormone cotisol but also cortisone and corticosterone. Cells of the zona fasciculata are larger than those of the glomerulosa, have centrally located vesicular nuclei and are often binucleated. Their cytoplasm is lightly basophilic with numerous lipid droplets, mitochondria and short microvilli on the apical surface that extend into capillary sinusoids.

Cortisol down regulates the immune system and suppresses inflammation by inhibition of lymphocyte production and turnonver. It also modulates carbohydrate metabolism by promoting formation of glucose from protein during a starvation scenario. Cortisol is under negative feedback control from corticotrophs in the anterior pituitary (which release ACTH) and hypothalamic neurosecretory cells (which secreted corticotrophin releasing hormone).

The zona reticularis is the deepest zone of secretory cells and are adjacent to the medulla. Like other endocrine organs, it has irregular anastomosing cords separated by sinusoids. Cells in the reticularis are smaller than those in the fasciculata and have deep staining nuclei. They have few lipid droplets in the cytoplasm but numerous secondary lysosomes and lipofuscin pigment granules. The zona reticularis secrete residual amounts of cortisol and several weak androgens.


 * 7. Describe the functions of each hormone secreted by the adrenal gland and the clinical disorders associated with each.**

Zona glomerulosa secrets aldosterone and deoxycorticosterone. These minerocorticoids act to promote resorption of Na+ from the distal convoluted tubules of the kidney, sweat glands, and salivary glands. Their secretion is primarily controlled by the renin/angiotensin system and secondarily by ACTH secretion from the anterior pituitary.

Zona fasciculata secretes glucocorticoids, primarily cortisol, cortisone and corticosterone. These glucocorticoids modulate the immune system, down-regulating response and inflammation by inhibiting production and turnover of lymphocytes (T cells and B cells). It also modulates carbohydrate metabolism, promoting formation of glucose from protein. Cortisol is under negative feedback control by ACTH from the anterior pituitary (corticotrophs) and CRH from the hypothalamus (hypothalamic neurosecretory cells).

Zona reticularis secretes residual amounts of cortisol and also several weak steroid androgens. These secretions are normally not physiologically significant.

Adenomas are tumors of the zona reticularis cells that secrete large amount of androgens. In prepubescent males, this can cause precocious development of sex organs and secondary sexual characteristics. In females, adrenogenital syndrome can result with androgenization of genitalia, development of male secondary characteristics, and pseudohermaphroditism in severe cases.

Patients with Addison’s disease typically have a darkening of their exposed skin, lower blood pressure and weakness. Addison’s disease is primarily a hypoadrenalism with idiopathic atrophy of the adrenal cortex. Decreased glucocorticoids results in weakness and drowsiness due to low blood glucose. Decreased minerocorticoids results in decreased blood pressure, decreased extracelluar fluid volume, and decreased resorption of Na+ and Cl- ions in the kidneys. ACTH secretion is typically increased.

Cushing’s disease is primarily a hyperadrenalism resulting from adrenal cortical tumors or excessive synthetic glucocorticoid use. Patients typically have a redistribution of fat around neck, face (moonface), and abdomen. Thinning of skin and loss of fat in the hypodermis causes underlying blood vessels to show through, exhibiting a characteristic blush. Excessive glucocorticoids results in antianabolic effects on protein synthesis, causing wasting of limb musculature, and thinning of bones. Lastly, patients are typically hyperglycemic, due to loss of proper glucocorticoid modulation.

The adrenal medulla releases catecholamines: epinephrine and norepinephrine. Catecholamines reinforce actions of the sympathetic nervous sytem in preparation for dealing with stress. Specifically, they cause elevated plasma glucose levels by stimulating glycogenolysis, increase blood pressure and cardiac output, dilate the coronary and skeletal muscle blood vessles, and cause cutaneous vasoconstriction. Release is controlled by sympathetic branches of the autonomic nervous system in response to environmental and emotional stress.


 * 8. Describe the organization of the adrenal medulla and its constituent cells.**

Chromafin cells arranged in irregular clumps between wide fenstrated capillaries.


 * 9. Indicate which cells of the adrenal medulla secrete hormones, and identify the hormones secreted by each.**

Chromaffin cells of the adrenal medulla are divided into epinephrine cells and norepinephrine cells which can only be distinguished by immunohistochemistry. Epinephrine cells have round granules and tend to cluster around adrenal sinusoids. Norepinephrine cells have flattened or ovoid granules and tend to cluster around adrenal arterioles.

Epinephrine is synthesized from norepinephrine via addition of a methyl group. The enzyme that catalyzes this methylation is glucocorticoid-induced. That is, the norepinephrine in cells closest to the adrenal sinusoids and farthest from the adrenal arterioles are bathed in glucocorticoids secreted by the adrenal cortex and become methylated to epinephrine. The norepinephrine in cells farther away from the adrenal sinusoids and closes to adrenal arterioles are not methylated and remain norepinephrine.

Release of catecholamines from the adrenal medulla result from neural impulses from their preganglionic fibers of the autonomic system via splanchnic nerve and is Ca+ dependent.


 * 10. Identify the endocrine component of the pancreas, the specific hormone producing cells and the functions of each hormone.**

The endocrine pancreas consists of the islets of Langerhans which are multihormonal endocrine microorgans situated within the parenchyma of the pancreas among the pancreatic acini. These cells secrete several hormones involved in stimulation of digestion and regulation of glucose transfer. Each islet consists of small clusters containing up to several hundred endocrine cells and appear to be more concentrated in the tail of the pancreas. Pancreatic islets are arranged in cords separated by a dense network of fenestrated capillaries and encapsulated by a delicate network of reticular fibers that support the parenchymal cells and separate them from the surrounding pancreatic acini. Islet cells are typically more pale and smaller than cells of pancreatic acini. Five distinct cell types have been identified: alpha, beta, delta, F and G cells. Alpha cells are located near the periphery of the islet and have an indented nuclus. They secrete Glucagon which signals the release of glucose from glycogen by the liver, raising blood glucose levels.

Beta cells are small and concentrated in the center of islets. They secrete insulin which signals the transfer of glucose from plasma to target tissues and stimulates the conversion of glucose to glycogen in the liver. Diabetes mellitus type I early onset involves the reduced beta cell secretion of insulin. Type II late onset involves the defect of insulin receptors despite normal beta cell insulin secretion. Diabetes mellitus is characterized by hyperglycemia due to decreased tissue uptake of glucose from plasma, increase glucose in urine (glucosuria), and increased excretion of water (polyuria).

Delta cells are larger than alpha and beta cells. These cells secrete somatostatin which acts as a neurotransmitter in the brain and a hormone in other tissues. In the hypothalamus, somatostatin inhibits growth hormone (somatotrophin) release. In the pancreas, somatostatin functions as a paracrine hormone, inihibiting the release of glucagon and insulin.

Alpha, beta, and delta cells appear to be connected by gap junctions, allowing their secretions to affect each other by local diffusion (paracrine) effects. Glucogon and insulin release by alpha and beta cells, respectively, is regulated primarily by direct feedback of plasma glucose.

F cells secrete pancreatic polypeptide which stimulates the release of gastric secretions in the gut and inhibits bile release from the gall bladder. However, pancreatic polypeptide is not a primary regulator of either function.

G cells secrete gastrin which increases HCL secretion and increases gastric motility.