5/8/18 Anatomy and histology of the endocrine system

Describe the anatomy and histology of the adrenals

2 well demarcated tissue components: *Cortex* surrounds the medulla. The cortex is bright yellow-orange due to the large amount of lipid (the cortex produces only steroid hormones) *Medulla* is more red-brown to grey, and may have a similar gross appearance to neural tissue

Describe the histology of the posterior pituitary

Neuropil background Herring bodies: where hormones are stored Pituicytes: support cells

What are some of the organizational patterns of endocrine tissues

Note: BL image is actually parathyroid, not zona fasciculata

What are pituicytes? What are Herring bodies?

Pituicytes: specialized glial cells Herring bodies: swellings of the distal axons where hormones are stored

Describe the embryology of the parathyroid glands

Superior parathyroid - pouch 4 Inferior parathyroid - pouch 3

Describe the histology of the pancreas

*Acinar cells*: exocrine component (makes proenzymes) *Islet cells*: endocrine. Lighter cells that form nest within spherical body. More numerous in the tail of pancreas

What are the 3 different cells in the pancreas (note: cannot be distinguished histologically - must use immunohistochemistry)

*Alpha cells*: produce glucagon (peripheral in islet) *Beta cells*: produce insulin (central in islet) *Delta cells*: produce somatostatin (scattered in islet)

What are the divisions of the pituitary glands?

*Anterior pituitary (adenohypophysis)*: - Anterior lobe (pars distalis) - Intermediate lobe (pars intermedia) - Pars tuberalis (surrounds pituitary stalk, separated from anterior lobe by a fibrous trabecula) *Posterior pituitary (neurohypophysis)* - Median eminence (accepts axons of hypothalamic nuclei carrying stimulatory and releasing factors that enter the hypophyseal portal system) - Infundibular stalk, which carries axons arising from hypothalamic nuclei that continue on to the infundibular process - Infundibular process itself (pars nervosa)

What are C cells? Where are they located and what do they produce?

*C cells (parafollicular cells)* are scattered in follicles inside the basement membrane of the throid, but not in contact with colloid, as well as outside follicles Produce the peptide hormone *calcitonin*, which is stored in vesicles and secreted in response to ↑ blood Ca

Describe the histology of the parathyroids. What are the important cell types?

*Chief cells*: secrete parathyroid hormone (↑ serum Ca). Round, forms small clusters/rosettes *Oxyphil cells*: function unknown. Big, bright pink cells, very eosinophilic, granular cytoplasm. Also lots of fat (adipose)

Describe the histology of the medulla

*Chromaffin cells*: produce epinephrine, norepinephrine Sustentacular cell Adrenal vein

What are the different types of soluble cell signaling?

*Endocrine:* Signal (hormone) travels through blood stream to reach distant target cell Must have good vasculature *Paracrine:* Signal travels through extracellular space to reach nearby target cell *Autocrine:* Signal travels through extracellular space and binds to the cell producing it Negative feedback or amplification at a cellular level

What are the important nuclei involved in hypothalamic-pituitary connections?

*Paraventricular nucleus* produces oxytocin *Supraoptic nucleus* produces antidiuretic hormone (ADH), vasopressin *Ventral nucleus* produces releasing factors and inhibitory hormones for anterior pituitary

• Compare and contrast the cellular biology of different endocrine tissues. • Describe the gross anatomy of the major endocrine glands. • Explain the embryologic development of the major endocrine glands. • Characterize the microscopic anatomy (histology) of the major endocrine glands. • List the relevant hormones produced by each cell type in the major endocrine glands.

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Name two important general rules of endocrine tissues

A given endocrine tissue generally produces one biochemical type of hormone (i.e., peptide, steroid, or amino acid derivative) A given endocrine tissue may produce more than one specific hormone, but each cellin that tissue generally produces only one hormone.

What is a tropic hormone?

A hormone that acts upon another endocrine gland, whereas a direct hormone acts on some other non-endocrine tissue

How do acidophils stain on H&E? What is their function?

Acidophils stain red on H&E and secrete simply polypeptide hormones. They include two main types: 1) *Somatotrophs*, which secrete growth hormone. They account for 40-50% of the cellularity and are more concentrated in the lateral aspect of the gland 2) *Lactotrophs*, which secrete prolactin. They account for 15-20% of the cellularity and are scattered throughout the gland

Describe the dual embryonic origin of the pituitary gland

Adenohypotohysis arises from *Rathke's pouch*, an outpouching of oral ectoderm at the roof of the mouth The neurohypophysis is an outpouching of the neural tube from the floor of the 3rd ventricle that retains its connection with the remainder of the CNS as it differentiates into the infundibular stalk and pars nervosa

How do basophils stain on H&E? What is their function?

Basophils stain blue-purple on H&E and secrete glycoprotein hormones. They include three main types: 1) *Corticotrophs*, which secrete adrenocorticotropic hormone (ACTH). (ACTH can be further processed to form melanocyte stimulating hormone (MSH) and β-lipotropic hormone.) They account for 15-20% of the cellularity and are more concentrated in the medial aspect of the gland 2) *Thyrotrophs*, which secrete thyroid stimulating hormone (TSH). They account for 5% of the cellularity and are more concentrated in the anterior aspect of the gland. 3) *Gonadotrophs*, which secrete follicle stimulating hormone (FSH) and luteinizing hormone (LH). They account for 10% of the cellularity and are scattered throughout the gland.

Describe the embryologic origins of the thyroid

Begins as an outpouching of oral endoderm from the floor of the mouth, between the anterior 2/3 and the posterior 1/3 of the tongue. This outpouching is called the *thyroid diverticulum* and the opening at its superior aspect is the foramen cecum. The thyroid gland descends in the anterior midline through the thyroglossal duct, past the hyoid bone, thyroid cartilage, and cricoid cartilage to find its final position in the anterior-inferior neck

Describe the circulatory aspect of the hypothalamic-pituitary connections

Blood flow between the hypothalamus and anterior pituitary is important because it is through this hypophyseal portal system that stimulatory and inhibitory hormones travel from the hypothalamus to the anterior pituitary. Blood flow originates from the superior hypophyseal artery, which branches to form a capillary bed called the primary plexus The primary plexus surrounds axon terminals of hypothalamic neurons in the stalk. When APs cause release of these stimulatory or inhibitory hormones from hypothalamic neurons, they enter the primary plexus and flow into hypophyseal portal veins, which then give rise to a second plexus in the pars distalis of the anterior pituitary. This second capillary bed delivers these stimulatory and inhibitory hormones from the portal system and also receives hormones secreted by the anterior pituitary, which act at various tissues throughout the body Note: these blood vessels lie outside the blood-brain barrier.

How do Chromophobes stain on H&E? What is their function?

Chromophobes stain relatively clear on H&E and are non-secretory. They are usually thought of as cells that have already discharged their hormones. They may also serve as a stem cell reserve for the other cell types.

What are the different types of endothelial cell linings? Which type do endocrine organs have?

Continuous, fenestrated, and sinusoid The capillaries of endocrine tissues have *fenestrated endothelial cell linings*. *Fenestrations* are small pores within the endothelial cells that increase their permeability to large molecules, like many hormones Especially important for peptide-based hormones

Describe the embryology of the adrenals

Fetal cortex: intermediate mesoderm Permanent cortex: coelomic Mesoderm medulla: neural crest

Describe the histology of the thyroid

Follicular epithelium is arranged as cuboidal epithelium surrounding a central mass of secreted *thyroglobulin (colloid)* and bounded on the outside by a basal lamina *Follicular cells* - free triiodothyronine (T3) and thyroxine (T4) *C cells (parafollicular cells)*: calcitonin (think clear cells)

Describe the 4 anatomical parts of the pancreas

Head, body, tail, uncinate process ("hook")

Which of the following correctly pairs an endocrine cell type with the hormone it produces? A. δcell—somatostatin B. Basophil—vasopressin C. Oxyphil—parathormone D. Chief cell—calcitonin E. α cell—insulin

The answer is (A). Delta cells are components of the islets of Langerhans and produce somatostatin. The other major islet cells include alpha cells, which produce glucagon, and beta cells, which produce insulin. (A) (correct answer) (B) Basophils produce FSH, LH, ACTH, and TSH. Vasopressin is produced by hypothalamic neurons (specifically, those in the supraoptic nucleus). (C) There are no known major secretory products of oxyphils. Parathormone is produced by chief cells. (D) Chief cells produce parathormone. Calcitonin is produced by thyroid C-cells. (E) Alpha cells produce glucagon. Insulin is produced by beta cells.

Each of the following endocrine tissues is derived from embryonic endoderm EXCEPT the: A. anterior pituitary. B. follicular epithelium of the thyroid. C. superior parathyroid glands. D. inferior parathyroid glands. E. islets of Langerhans.

The answer is (A). The anterior pituitary derives from an outgrowth of oral ectodermcall Rathke's pouch. (A) (correct answer) (B) The follicular epithelium of the thyroid derives from the thyroid diverticulum, an outpouching of oral endoderm at the base of the tongue. (C) The superior parathyroid glands derive from pharyngeal pouch 4, which develops from endoderm associated with the pharyngeal apparatus. (D) The inferior parathyroid glands derive from pharyngeal pouch 3, which develops from endoderm associated with the pharyngeal apparatus. (E) The islets of Langerhans derive from duodenal endoderm growing into the ventral and dorsal mesenteries as ventral and dorsal pancreatic buds, respectively.

Which of the following gives rise to the inferior parathyroid glands? A. Ultimobranchial body B. Second pharyngeal pouch C. Third pharyngeal pouch D. Fourth pharyngeal pouch E. Foramen cecum

The answer is (C). The inferior parathyroid glands arise from the third pharyngeal pouch, along with the thymus. This explains why they may be found as low as inside the thymus itself. (A) The ultimobranchial body gives rise to the cells that mature into thyroid C-cells. (B) The second pharyngeal pouch gives rise to the palatine tonsils. (C) (correct answer) (D) The fourth pharyngeal pouch gives rise to the superior parathyroid glands, as well as the ultimobranchial body. (E) The foramen cecum is a blind-ending divot in the tongue base that represents the initial proximal opening of the thyroglossal duct.

Which of the following is true regarding the adenohypophysis? A. It receives direct innervation by the supraoptic nucleus. B. The basophils within it produce growth hormone. C. It is supported by modified glial cells called pituicytes. D. The acidophils within it produce prolactin. E. It develops from the neural tube.

The answer is (D). Acidophils are red-staining cells of the anterior pituitary (adenohypophysis) and produce growth hormone and prolactin. (A) This statement is true regarding the posterior pituitary. (B) Basophils produce FSH, LH, ACTH, and TSH. (C) This statement is true regarding the posterior pituitary. (D) (correct answer) (E) This statement is true regarding the posterior pituitary.

A 15-year-old female is brought to her pediatrician for a mass growing at the base of her tongue. A biopsy demonstrates unremarkable thyroid tissue. This location for ectopic thyroid tissue is common because, during development, the thyroid: A. receives incoming C-cells from the ultimobranchial body. B. arises near the sulcus terminalis and descends into the cervical sinus. C. arises in the lateral endoderm and moves toward the midline. D. arises at the foramen cecum and descends down the thyroglossal duct. E. arises from the third and fourth pharyngeal pouches.

The answer is (D). The thyroid gland originates at the foramen cecum and descends down the thyroglossal duct to reach its final position in the lower anterior neck. Ectopic thyroid tissue may be found anywhere along this track, including at the base of the tongue, in the midline neck (a thyroglossal duct cyst may also create a mass here), or projecting from the isthmus of the thyroid as a pyramidal lobe. (A) The thyroid does indeed receive C-cells from the ultimobranchial body, but this answer fails to explain why the base of the tongue is a common location for ectopic thyroid tissue. (B) The thyroid does arise near the sulcus terminalis (the foramen cecum is found at the apex of the sulcus), but the thyroid descends down the thyroglossal duct. The cervical sinus is created when the second, third, and fourth pharyngeal clefts overgrow on the lateral aspect of the pharyngeal apparatus and is normally obliterated in postnatal life. (C) The thyroid derives from midline endoderm; the pharyngeal pouches derive from lateral endoderm. (D) (correct answer) (E) The parathyroids, thymus, and ultimobranchial bodies derive from the third and fourth pharyngeal pouches; the thyroid receives C-cells from the ultimobranchial body, but this answer again fails to explain why the base of the tongue is a common location for ectopic thyroid tissue.

Cushing syndrome may be caused by hyperplasia or an adenomatous growth of the cells of the zona fasciculata. As such, the cells that make up this tumor would be expected to have what cytologic appearance? A. Duotone cytoplasm with deep blue on one side, pink on the other B. Dense blue cells with little cytoplasm C. Cells with highly eosinophilic, solid cytoplasm D. Cuboidal cells with extracellular hormone stores E. Cells with vacuolated pink to clear cytoplasm

The answer is (E). The zona fasciculata contains cells that produce cortisol. The zona fasciculata is composed of cords of cells with "frothy," vacuolated pink to clear cytoplasm. As such, tumors arising from these cells often recapitulate the same cytology. (A) This is a good description of a pancreatic acinar cell, or other cells that produce lots of enzymatic secretions. (B) This is a good description of lymphocytes. (C) This is a good description of acidophils of the anterior pituitary, as well as many other cell types. (D) This is a good description of thyroid follicular epithelium. (E) (correct answer)

What are chromaffin cells?

The chromaffin cells of the adrenal medulla produce catechol amines (epinephrine and, to a lesser extent, norepinephrine), which are stored in cytoplasmic dense granules. As a "displaced" prevertebral ganglion, it receives innervation from cholinergic splanchnic nerves and are under control of the sympathetic NS. Thus the chromaffin cells are like postsynaptic sympathetic neurons that simply secrete their products into the blood stream through the adrenal vein, rather than down an axon.

Describe the zona reticularis

The deepest layer of the adrenal cortex; produces *androgens* (most notably *DHEA* and *androstenedione*) under the stimulation of ACTH. Histologically, it contains a net-like pattern of small pink cells.

Why are the pharyngeal pouches relevant to the formation of the thyroid?

The fourth pharyngeal pouch gives rise to the ultimobranchial body, which travels inferomedially toward the substance of the thyroid gland to give off the cells that travel into the gland and terminally differentiate into C-cells.

Describe the zona fasciculata

The middle layer of the adrenal cortex; produces *glucocorticoids* (most notably *cortisol*) under the stimulation of ACTH. Histologically, it contains cords of pink to clear, "frothy" cells. This "froth" represents lipid vacuoles containing cholesterol esters.

Describe the zona glomerulosa

The most superficial layer of the adrenal cortex; produces *mineralocorticoids* (most notably *aldosterone*) under the stimulation of *angiotensin II* (although ACTH also mildly stimulates this layer). Histologically, it contains small balls of small, purple cells.

Describe the embryology of the pancreas

The pancreas develops as two separate buds: The ventral pancreatic bud is a subdivision of the hepatic diverticulum, a growth of duodenal endoderm that fills in the ventral mesentery. The hepatic diverticulum also gives rise to the liver and gallbladder, as well as the biliary tree. The dorsal pancreatic bud emerges separately as a growth of duodenal endoderm into the dorsal mesentery After these buds form, the ventral bud begins to rotate clockwise around the duodenum, carrying the biliary tree with it. The two buds meet to the left of the duodenum and fuse together, forming the mature pancreas.

Describe the location of the pituitary gland

The pituitary resides on the ventral surface of the brain, just inferior to the optic chiasm into which the optic nerves enter (and, at least partially, cross the midline). This relationship is of clinical significance: a pituitary adenoma may grow upward and compress the optic chiasm, causing a characteristic visual field defect (bitemporal hemianopsia). The pituitary is also just medial to the uncus of the temporal lobe, and anterior to the brainstem. Close relationship between the hypothalamus and pituitary (via the pituitary stalk) Sella turcica (sphenoid bone) is next to the sphenoid sinus, allowing surgical access

Describe the histology of the pituitary

The posterior lobe is much pinker, like brain tissue (due to the high amount of neuropil and relative paucity of nuclei) The anterior pituitary is much more blue-purple, given its increased cellular density The red spotting in the anterior pituitary demonstrates the high vascularity of this gland

What structure is at risk for a lesion during thyroid surgery?

The recurrent laryngeal nerves (lie just behind thyroid itself)

FLIP QUICKLY! This is the answer card. Prompt and image on other side. - - - This is an islet of Langerhans, identifiable by its relatively spherical shape and sieve-like pattern of cellularity. The red cells in question are relatively few in number and concentrated at the periphery of the islet; thus, they likely represent α cells, which produce glucagon. The answer is (C). (A) The structure in the image is an islet of Langerhans; aldosterone is produced by the zona glomerulosa of the adrenal cortex. (B) The structure in the image is an islet of Langerhans; follicle stimulating hormone is produced by gonadotrophs in the anterior pituitary (which are a subtype of basophil). (C) (correct answer) (D) The other (green) cells in the image are β cells, which are larger in number and more concentrated toward the internal aspect of the islet. They produce insulin. (E) The structure in the image is an islet of Langerhans; norepinephrine is produced by the chromaffin cells of the adrenal medulla (as well as certain neurons).

This image demonstrates immunofluorescent staining of an endocrine tissue. The blue circles represent nuclei, and the red and green cytoplasmic staining corresponds with different secretory products of those individual cells. The red cells* likely produce: A. aldosterone. B. follicle stimulating hormone. C. glucagon. D. insulin. E. norepinephrine.

Describe the histology of the anterior pituitary. What are the 3 major types of cells found here?

Three types of cells can be differentiated by routine (H&E) stains: acidophils, basophils, and chromophobes.

What is the main substance within colloid?

Thyroglobulin (a precursor to T3 and T4)

What are 3 different ways that endocrine cells store hormones?

Tissues that produce peptide or amino acid derivative hormones may use intracellular storage granules (as visualized in the upper left image by electron microscopy), or may store hormone extracellularly, as shown in the thyroid tissue to the upper right Tissues that produce steroid hormones tend to produce their hormones on demand, when stimulated by another (tropic) hormone or another stimulus

FLIP QUICKLY! This is the answer card. Prompt and image on other side. - - - The parathyroid contains quite a bit of fat, starting in puberty (clear cells in the image). In the parenchyma, there is an admixture of small, blue-purple cells (chief cells) and larger pink, granular cells (oxyphils). The answer is (B). (A) The thyroid is composed of spheres of follicular cells surrounding acellular pink material (colloid). (B) (correct answer) (C) The adrenal cortex is composed of cells with varying morphology, but the presence of fat and the characteristic combination of small blue cells and larger pink cells does not match any of the adrenal cortical layers. (D) The adrenal medulla is composed of larger lavender to purple cells and smaller, spindled sustentacular cells. (E) The pancreas contains nests of pale, polygonal cells with a background of duotone acinar cells.

What endocrine tissue is shown in this image? A.Thyroid B.Parathyroid C.Adrenal cortex D.Adrenal medulla E.Pancreas

What do follicular cells produce when stimulated by TSH?

When stimulated by TSH, follicular cells can also endocytose iodinated thyroglobulin at their apical end and break down the thyroglobulin to form *free triiodothyronine (T3) and thyroxine (T4)*, which are soluble and readily secreted at the basal end of the cell into adjacent capillaries. There, they are bound to carrier proteins (*thyroid binding globulin, TBG*).

What are the 3 layers of the adrenal cortex?

Zona glomerulosa Zona fasciculata Zona reticularis Order: GFR Products (from superficial to deep): Salt, sugar, sex