Lecture 11: Histology of Thyroid and Parathyroid

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Questions and Answers

What is the primary function of follicular cells in the thyroid gland?

  • Producing parathyroid hormone (PTH)
  • Synthesizing, storing, and secreting T3 and T4 (correct)
  • Secreting calcitonin to regulate calcium levels
  • Initiating immune responses within the thyroid

Steroid hormones exclusively bind to surface receptors on target cells.

False (B)

What is the gelatinous material found within thyroid follicles called, and what are its primary components?

colloid; thyroglobulin, enzymes, glycoproteins

The ultimobranchial body, derived from the ventral portion of pharyngeal pouch 4, induces migration of neural crest cells into the thyroid, which differentiate into _____________ cells.

<p>parafollicular</p> Signup and view all the answers

Match the following cell types with their respective hormone secretions:

<p>Thyroid Follicular Cells = T3 and T4 Thyroid Parafollicular Cells = Calcitonin Parathyroid Chief Cells = Parathyroid Hormone (PTH)</p> Signup and view all the answers

Which of the following best describes the role of TPO (thyroid peroxidase) in thyroid hormone synthesis?

<p>Adds iodine to tyrosine residues on thyroglobulin (A)</p> Signup and view all the answers

Increased levels of T3 and T4 stimulate the release of TRH (thyrotropin-releasing hormone) from the hypothalamus.

<p>False (B)</p> Signup and view all the answers

Name the two primary cell types found in the parathyroid gland.

<p>chief cells, oxyphil cells</p> Signup and view all the answers

In response to low blood calcium levels, the parathyroid gland secretes _______, which increases calcium resorption in the kidneys and stimulates bone resorption.

<p>parathyroid hormone</p> Signup and view all the answers

Match the following conditions with their primary cause related to thyroid function:

<p>Hypothyroidism = Iodine deficiency Hyperthyroidism = Excessive thyroid hormone production Goiter = Enlargement of the thyroid gland</p> Signup and view all the answers

What is the primary mechanism by which increased thyroid hormone (TH) levels affect body temperature?

<p>Increasing metabolic activities in target cells (A)</p> Signup and view all the answers

Increased body temperature stimulates secretion of TRH by the hypothalamus.

<p>False (B)</p> Signup and view all the answers

What embryological structure connects the thyroid primordium to the foramen cecum of the tongue, and what happens to this structure during development?

<p>thyroglossal duct; atrophies</p> Signup and view all the answers

The process by which undegraded thyroglobulin is transported via megalin receptors to the basolateral cell surfaces and exocytosed into the blood is called the ________ pathway.

<p>transepithelial</p> Signup and view all the answers

Match the following terms related to thyroid hormone synthesis with their correct definitions:

<p>MIT = Monoiodotyrosine, one iodine atom DIT = Diiodotyrosine, two iodine atoms TPO = Thyroid peroxidase NIS = Sodium/iodide symporter</p> Signup and view all the answers

Which of the following is a characteristic histological feature of the thyroid gland?

<p>Follicles filled with colloid. (B)</p> Signup and view all the answers

The concentration of iodide inside follicular cells is lower than in the blood.

<p>False (B)</p> Signup and view all the answers

What hormone is produced by the chief cells of the parathyroid gland?

<p>parathyroid hormone; PTH</p> Signup and view all the answers

Graves' disease is an autoimmune disorder characterized by abnormal immunoglobulins that bind to _________ cell TSH receptors, leading to continuous thyroid hormone production.

<p>follicular</p> Signup and view all the answers

Match the following clinical manifestations with the related thyroid disorder:

<p>Hypothyroidism = Cold intolerance and fatigue Hyperthyroidism = Heat intolerance and irritability Goiter = Enlarged thyroid gland</p> Signup and view all the answers

Which of the following best explains the developmental origin of parafollicular cells in the thyroid gland?

<p>Migration of neural crest cells (D)</p> Signup and view all the answers

The thyroid gland is located on the posterior surface of the trachea.

<p>False (B)</p> Signup and view all the answers

List three functions of T3 and T4 hormones.

<p>metabolism, heat production, body growth</p> Signup and view all the answers

The thyroid-stimulating hormone (TSH) is released by the __________ pituitary, which, in turn, stimulates the thyroid gland to produce T3 and T4.

<p>anterior</p> Signup and view all the answers

Match the following terms with the associated function they influence.

<p>Calcitonin = Blood calcium levels Parathyroid Hormone (PTH) = Calcium resorption</p> Signup and view all the answers

What cellular feature is characteristic of parathyroid oxyphil cells?

<p>Acidophilic cytoplasm filled with mitochondria (D)</p> Signup and view all the answers

Parathyroid glands are derived from pharyngeal pouches 1 and 2.

<p>False (B)</p> Signup and view all the answers

What is the role of the enzyme 5-deiodinase in the lysosomal pathway of thyroglobulin reabsorption?

<p>deiodinates T3, T4, DIT, MIT</p> Signup and view all the answers

In Hashimoto's thyroiditis, abnormal _________ attack thyroglobulin, TPO, and TSH receptors, leading to hypothyroidism.

<p>autoimmunoglobulins</p> Signup and view all the answers

Match the following symptoms with the associated thyroid related disease.

<p>Increased heart rate, weight loss = Hyperthyroidism Extreme fatigue, weight gain = Hypothyroidism</p> Signup and view all the answers

In which of the following conditions is there high PTH to compensate for hypocalcemia?

<p>Secondary hyperparathyroidism (D)</p> Signup and view all the answers

Calcitriol targets osteoclasts directly

<p>False (B)</p> Signup and view all the answers

In DiGeorge syndrome, what chromosome is the deletion in?

<p>22</p> Signup and view all the answers

Parafollicular cells are derived from Neural ______

<p>crest</p> Signup and view all the answers

Match each hormone with its function

<p>T3/T4 = Increases metabolism parathyroid hormone = Increase bone resorption via osteoclasts</p> Signup and view all the answers

What percentage of people approximately have 4 parathyroid glands?

<p>5% (B)</p> Signup and view all the answers

Most calcium resorption occurs in the kidneys.

<p>False (B)</p> Signup and view all the answers

Where do the parathyroid glands originate from?

<p>pharyngeal pouches 3 and 4</p> Signup and view all the answers

T3 concentration is _____ than T4 concentration in the blood.

<p>lower</p> Signup and view all the answers

Match the location with what vascular supply it recieves

<p>Thyroid Gland = Superior and Inferior thyroid arteries Parathyroid Gland = Inferior thyroid artery</p> Signup and view all the answers

Which of the following describes the action of steroid hormones?

<p>They can bind to either surface receptors or cytoplasmic receptors. (C)</p> Signup and view all the answers

The primary function of parafollicular cells in the thyroid is the synthesis and storage of thyroglobulin.

<p>False (B)</p> Signup and view all the answers

The thyroid gland originates from what embryonic structure?

<p>pharyngeal floor</p> Signup and view all the answers

In response to TSH stimulation, thyroglobulin is transported to ______ where it is degraded for hormone release.

<p>lysosomes</p> Signup and view all the answers

Match the following hormones with their roles in calcium regulation:

<p>Parathyroid Hormone (PTH) = Increases serum calcium levels by stimulating bone resorption and increasing calcium reabsorption in the kidneys. Calcitonin = Decreases serum calcium levels by inhibiting osteoclast activity and promoting calcium deposition in bone. Calcitriol (active Vitamin D) = Increases serum calcium levels by promoting calcium absorption in the intestines.</p> Signup and view all the answers

Flashcards

Cell-cell signaling

Communication between cells based on distance and chemical signals.

Hormone signaling

Hormones bind to surface or cytoplasmic receptors, triggering secondary messengers and cascades.

Homeostasis

Maintaining stable internal conditions via regulatory mechanisms.

Negative feedback

A regulatory mechanism where the end product inhibits its own production.

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Thyroid follicles

Functional units of the thyroid; sacs of colloid surrounded by follicular cells.

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Follicular cells

Simple cuboidal cells that surround the colloid in thyroid follicles; produce thyroglobulin.

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Colloid

Gelatinous substance in thyroid follicles; contains thyroglobulin.

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Parafollicular cells (C cells)

Larger cells between thyroid follicles; secrete calcitonin.

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Calcitonin

Hormone produced by thyroid parafollicular cells; lowers blood calcium.

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T3

Tri-iodothyronine, a thyroid hormone.

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T4

Tetra-iodothyronine (thyroxine), a thyroid hormone.

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Thyroglobulin

Glycoprotein synthesized by follicular cells; precursor to thyroid hormones.

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Thyroid Peroxidase (TPO)

Enzyme responsible for iodinating and coupling tyrosine residues in thyroglobulin.

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Graves' disease

Autoimmune disease causing hyperthyroidism.

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Goiter

Enlargement of the thyroid gland.

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Hashimoto's thyroiditis

Autoimmune disease causing hypothyroidism.

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Parathyroid Glands

Located on the posterior surface of the thyroid gland, regulates calcium levels.

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Parathyroid Cells

The two cell types are chief cells and oxyphil cells.

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Chief cells

More numerous and secrete parathyroid hormone (PTH).

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Parathyroid hormone (PTH)

Secrete parathyroid hormone; increase blood calcium by acting on bone, kidney, and intestine.

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Oxyphil cells

Less common, larger, acidophilic cells in the parathyroid with high mitochondrial content.

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Hyperparathyroidism

A condition of elevated PTH, leading to hypercalcemia; often caused by parathyroid adenoma.

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Hypoparathyroidism

A condition of decreased PTH, leading to hypocalcemia; can cause muscle spasms and convulsions.

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Study Notes

Cell-Cell Signaling

  • Cell-cell signaling can be defined based on the distance to the target.
  • Cell-cell signals are chemical in nature.

Hormone Signaling

  • Steroid hormones bind to surface or cytoplasmic receptors.
  • Hormone signaling often involves secondary messenger cascades.
  • Overall hormone secretion is controlled by feedback mechanisms.

Homeostasis

  • Feedback loops regulate homeostasis.
  • Negative feedback causes oscillation.
  • Stress or disturbance changes the internal environment and receptors detect the change.
  • Corrective measures are activated and counteract the change to return to the set point.

Thyroid Location and Anatomy

  • Pyramidal lobes extend upward from the isthmus in 40% of the population.
  • Accessory thyroid glands are isolated tissue masses that can occur anywhere between the hyoid and aortic arch.

Thyroid Histology

  • Thyroid gland functional units are follicles, ranging from 0.2 to 1.0 mm in diameter.
  • Follicular cells are simple cuboidal epithelium surrounding the colloid.
  • The colloid is a gelatinous material made of thyroglobulin, enzymes, and glycoproteins.
  • Parafollicular cells are larger cells located between follicles and near capillaries.
  • Blood capillaries surround follicles, and these capillaries are fenestrated.
  • The thyroid is the only endocrine gland that stores a large quantity of secretory product extracellularly, lasting up to 3 months without additional synthesis.

Thyroid Follicular (Principal) Cells

  • Follicular cells function in absorption and secretion.
  • They have slight basophilic and spherical nuclei.
  • Microvilli are located on the apical (colloid) surface.
  • The basal lamina covers the basal surface.
  • Follicular cells produce tri-iodothyronine (T3) and tetra-iodothyronine/thyroxine (T4).

Thyroid Parafollicular (C) Cells

  • Parafollicular cells are located between follicular cells and the basement membrane of the follicles, and are not exposed to the follicular lumen.
  • They can be solitary or in small clusters with Prominent Golgi bodies and Numerous secretory vesicles.
  • These cells are neural crest derivatives.
  • Parafollicular cells produce calcitonin hormone.

Thyroid Embryonic Development

  • Week 4: Endodermal thickening of the primitive pharyngeal floor (thyroid primordium) occurs just caudal to the 1st pharyngeal arch.
  • The thyroid primordium grows caudally as a ductlike invagination called the thyroglossal duct.
  • The thyroglossal duct remains connected to the foramen caecum of the tongue.
  • Week 5: Thyroglossal duct ends anterior to the trachea and divides into two lobes.
  • The duct atrophies during migration but may leave an embryological remnant.
  • Week 9: Endodermal cells differentiate into follicular cells.
  • Parafollicular cells are neural crest cells induced to migrate into the thyroid by the ultimobranchial body, which forms from the ventral portion of pharyngeal pouch 4.

Thyroid T3 and T4 Synthesis

  • The anterior pituitary releases thyroid-stimulating hormone (TSH; thyrotrophin) to stimulate synthesis and storage of thyroglobulin within follicular cells.
  • T3 is tri-iodothyronine, and T4 is tetra-iodothyronine (thyroxine).
  • T3 has a half-life of 1.5 days, and T4 has a half-life of 7 days.
  • T3 has 2-10x greater activity than T4.
  • Thyroglobulin precursor is synthesized in the rER and then transported to the lumen (colloid).
  • Iodide is actively pumped from blood into cells via NIS proteins; intracellular [iodide] is 30-40x greater than blood serum.
  • Pendrin transports iodide into the colloid, and it is immediately oxidized by TPO into iodine.
  • TPO adds iodine (1-2) to tyrosine residues of thyroglobulin and if one iodine is added, it’s MIT, and if two iodine atoms are added, it’s DIT.
  • Oxidative coupling produces T3 and T4; MIT + DIT = T3, and DIT + DIT = T4.
  • These remain attached to a thyroglobulin molecule.
  • Reabsorption in response to TSH follows 2 paths: Lysosomal & Transepithelial.
  • (5-L) endocyted thyroglobulin is transported to endosomes or mature lysosomes and is deionized by 5-deiodinase to free up T3, T4, DIT, and MIT, which is normally how the thyroid functions.
  • (5-TE) undegraded thyroglobulin is transported via megalin receptors to the basolateral cell surfaces and is exocytosed to the blood.
  • This avoids the lysosomal pathway.
  • The release ratio of T4 to T3 is 20:1 and T3 is 5x more active, so most is converted by organs from T4.
  • As thyroglobulin folds into its tertiary structure, iodinated tyrosines are brought into close proximity. Oxidative coupling reactions join two iodinated tyrosines.

Thyroid Functions

  • T3 and T4 functions regulate metabolism, heat production, and body growth/development.
  • Calcitonin functions modify blood calcium levels.

Thyroid Feedback Loop with Pituitary

  • A stimulus (e.g., low body temperature) causes the hypothalamus to secrete thyrotropin-releasing hormone (TRH), which acts on the anterior pituitary.
  • Thyrotropic cells in the anterior pituitary release thyroid-stimulating hormone (TSH).
  • TSH stimulates follicular cells of the thyroid gland to release thyroid hormone (TH).
  • TH stimulates target cells to increase metabolic activities, resulting in an increase in basal body temperature.
  • Increased body temperature is detected by the hypothalamus, and secretion of TRH by the hypothalamus is inhibited.
  • TH also blocks TRH receptors on the thyrotropic cells, inhibiting synthesis and release of TSH.,
  • TH effects take several hours to reach peak levels and Calcitonin effects reach peak in about 1 hour.

Clinical Thyroid Conditions

  • Hypothyroidism: caused by iodine deficiency or autoimmune issues resulting in Fatigue, low HR, cold intolerance, weight gain, and enlarged thyroid.
  • Hyperthyroidism: excessive thyroid hormone in circulation causing Irritability, high HR, heat intolerance, weight loss, and enlarged thyroid.
  • Goiter is either diffuse or multinodular and presents with enlarged follicular lumens (increased colloid).
  • In Hashimoto’s (autoimmune) thyroiditis, abnormal autoimmunoglobulins attack thryoglobulin, TPO, and TSH receptors.
  • Low thyroid hormone stimulates more TSH, which causes attempted overproduction of thyroglobulin, enlarging the thyroid gland early on (goiter).
  • Continued lymphocyte attacks destroy thyroid cells, and the gland shrinks over time (no goiter).
  • In Graves disease is caused by abnormal immunoglobulins that bind to follicular cell TSH receptors & trigger cAMP activity.
  • This causes continuous thyroid hormone production but normal TSH levels due to negative feedback.
  • The thyroid hypertrophies and colloid gets depleted from contact with the apical follicular surface.
  • One result of Graves disease may be Ophthalmopathy which occurs in 30% of patients.

Parathyroid Location and Histology

  • Parathyroid gland is near the thyroid but very different histology.
  • Paired superior and inferior parathyroid glands are located on the posterior surface of the thyroid.
  • Each gland is surrounded by a thin CT capsule and contains has two primary cell types the Chief (or principal) cells, and Oxyphil cells.
  • Blood capillaries - fenestrated

Parathyroid Chief (Principal) Cells

  • Slightly acidophilic cytoplasm and these are Small cells (7-10um diameter).
  • Chief cells have Numerous vesicles in cytoplasm and have lipid droplets and glycogen stores.
  • They Synthesize, store and secrete parathyroid hormone (PTH).
  • Chief cells Differentiate during embryonic development and regulate fetal calcium metabolism.

Parathyroid Oxyphil Cells

  • Larger than chief cells, more rounded and exhibit Acidophilic cytoplasm.
  • Oxyphil cells mitochondria fill cytoplasm and have No secretory vesicles.
  • Little rER present and are Present in parathyroid singly or in clusters, more common in older people.
  • Function uncertain and Differentiate at puberty.
  • Parathyroid glands contain More than 50% adipocytes in older people.
  • Up to 10% have parathyroid attached to the thymus.

Parathyroid Embryonic Development

  • Pharyngeal pouch 3 derivations: the dorsal portion forms inferior parathyroid and the ventral portion forms the thymus.
  • Pharyngeal pouch 4 derivations: dorsal portion forms the superior parathyroid and the ventral portion forms the ultimobranchial body.
  • The ultimobranchial body induces migration & differentiation of neural crests into parafollicular cells of the thyroid (~wk 7).
  • Approximately 5% of people have more than 4 parathyroid glands.
  • Parathyroids can be ectopically located in the neck and upper thorax.
  • DiGeorge syndrome: involves deletion of the long (‘q’) arm of chromosome 22.
  • This occurs in approximately 1:4000 births and results in hypoplasia of 3rd & 4th pharyngeal pouch derivatives.
  • Digeorge syndrome also can lead to thymic hypoplasia (immunodeficiency), hypoparathyroidism (missing or hypoplastic inferior parathyroid glands), seizures (hypocalcemia), heart defects (mild-severe), and abnormal facial features (underdeveloped chin & low set ears).

Parathyroid Function

  • Parathyroid hormone (PTH) causes increased serum Ca2+ and reduction serum phosphate.
  • PTH affects multiple targets in bone and Directly targets osteoprogenitor, osteoblasts, & osteocytes and Indirectly targets osteoclasts thru osteoblasts to increase bone resorption and release calcium & phosphate.
  • In the Kidneys stimulation of tubular resorption of Ca2+ and increase secretion of phosphate occurs.
  • PTH activates a hormonally active version of vitamin D3 ((Calcitriol: 1,25-(OH)2D3)) and acts in concert with PTH.
  • In the Intestines increased Ca resorption occurs (although not as well as vitamin D3).
  • Calcitriol also affects renal absorption and osteoclasts.
  • When high level of Ca²+ is in blood it stimulates the thyroid gland, which causes Parafollicular cells to release more calcitonin.
  • PTH effects take several hours to reach peak levels and Calcitonin effects reach peak in about 1 hour.
  • When it comes to Parathyroid conditions:
  • Primary hyperparathyroidism = high PTH due to abnormal parathyroid causing Increased serum Ca2+ levels (hypercalcemia) in which often see pathological deposits of Ca2+ (kidney stones), and results in 'weak' bone, CNS & PNS depression, and most common in adult over 69yo.
  • Secondary hyperparathyroidism = high PTH to compensate for hypocalcemia due to Vitamin D deficiency with resulting Rickets (children), and Osteomalacia (adults).
  • Hypoparathyroidism = low PTH resulting in Decreased serum Ca2+ levels (hypocalcemia), dense bone, spastic muscle contractions, and generalized convulsions and the treatment is to increase Ca2+ uptake from the gut with Vitamin D/calcium supplements.

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