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Questions and Answers
What is the primary function of follicular cells in the thyroid gland?
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.
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?
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.
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.
Match the following cell types with their respective hormone secretions:
Match the following cell types with their respective hormone secretions:
Which of the following best describes the role of TPO (thyroid peroxidase) in thyroid hormone synthesis?
Which of the following best describes the role of TPO (thyroid peroxidase) in thyroid hormone synthesis?
Increased levels of T3 and T4 stimulate the release of TRH (thyrotropin-releasing hormone) from the hypothalamus.
Increased levels of T3 and T4 stimulate the release of TRH (thyrotropin-releasing hormone) from the hypothalamus.
Name the two primary cell types found in the parathyroid gland.
Name the two primary cell types found in the parathyroid gland.
In response to low blood calcium levels, the parathyroid gland secretes _______, which increases calcium resorption in the kidneys and stimulates bone resorption.
In response to low blood calcium levels, the parathyroid gland secretes _______, which increases calcium resorption in the kidneys and stimulates bone resorption.
Match the following conditions with their primary cause related to thyroid function:
Match the following conditions with their primary cause related to thyroid function:
What is the primary mechanism by which increased thyroid hormone (TH) levels affect body temperature?
What is the primary mechanism by which increased thyroid hormone (TH) levels affect body temperature?
Increased body temperature stimulates secretion of TRH by the hypothalamus.
Increased body temperature stimulates secretion of TRH by the hypothalamus.
What embryological structure connects the thyroid primordium to the foramen cecum of the tongue, and what happens to this structure during development?
What embryological structure connects the thyroid primordium to the foramen cecum of the tongue, and what happens to this structure during development?
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.
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.
Match the following terms related to thyroid hormone synthesis with their correct definitions:
Match the following terms related to thyroid hormone synthesis with their correct definitions:
Which of the following is a characteristic histological feature of the thyroid gland?
Which of the following is a characteristic histological feature of the thyroid gland?
The concentration of iodide inside follicular cells is lower than in the blood.
The concentration of iodide inside follicular cells is lower than in the blood.
What hormone is produced by the chief cells of the parathyroid gland?
What hormone is produced by the chief cells of the parathyroid gland?
Graves' disease is an autoimmune disorder characterized by abnormal immunoglobulins that bind to _________ cell TSH receptors, leading to continuous thyroid hormone production.
Graves' disease is an autoimmune disorder characterized by abnormal immunoglobulins that bind to _________ cell TSH receptors, leading to continuous thyroid hormone production.
Match the following clinical manifestations with the related thyroid disorder:
Match the following clinical manifestations with the related thyroid disorder:
Which of the following best explains the developmental origin of parafollicular cells in the thyroid gland?
Which of the following best explains the developmental origin of parafollicular cells in the thyroid gland?
The thyroid gland is located on the posterior surface of the trachea.
The thyroid gland is located on the posterior surface of the trachea.
List three functions of T3 and T4 hormones.
List three functions of T3 and T4 hormones.
The thyroid-stimulating hormone (TSH) is released by the __________ pituitary, which, in turn, stimulates the thyroid gland to produce T3 and T4.
The thyroid-stimulating hormone (TSH) is released by the __________ pituitary, which, in turn, stimulates the thyroid gland to produce T3 and T4.
Match the following terms with the associated function they influence.
Match the following terms with the associated function they influence.
What cellular feature is characteristic of parathyroid oxyphil cells?
What cellular feature is characteristic of parathyroid oxyphil cells?
Parathyroid glands are derived from pharyngeal pouches 1 and 2.
Parathyroid glands are derived from pharyngeal pouches 1 and 2.
What is the role of the enzyme 5-deiodinase in the lysosomal pathway of thyroglobulin reabsorption?
What is the role of the enzyme 5-deiodinase in the lysosomal pathway of thyroglobulin reabsorption?
In Hashimoto's thyroiditis, abnormal _________ attack thyroglobulin, TPO, and TSH receptors, leading to hypothyroidism.
In Hashimoto's thyroiditis, abnormal _________ attack thyroglobulin, TPO, and TSH receptors, leading to hypothyroidism.
Match the following symptoms with the associated thyroid related disease.
Match the following symptoms with the associated thyroid related disease.
In which of the following conditions is there high PTH to compensate for hypocalcemia?
In which of the following conditions is there high PTH to compensate for hypocalcemia?
Calcitriol targets osteoclasts directly
Calcitriol targets osteoclasts directly
In DiGeorge syndrome, what chromosome is the deletion in?
In DiGeorge syndrome, what chromosome is the deletion in?
Parafollicular cells are derived from Neural ______
Parafollicular cells are derived from Neural ______
Match each hormone with its function
Match each hormone with its function
What percentage of people approximately have 4 parathyroid glands?
What percentage of people approximately have 4 parathyroid glands?
Most calcium resorption occurs in the kidneys.
Most calcium resorption occurs in the kidneys.
Where do the parathyroid glands originate from?
Where do the parathyroid glands originate from?
T3 concentration is _____ than T4 concentration in the blood.
T3 concentration is _____ than T4 concentration in the blood.
Match the location with what vascular supply it recieves
Match the location with what vascular supply it recieves
Which of the following describes the action of steroid hormones?
Which of the following describes the action of steroid hormones?
The primary function of parafollicular cells in the thyroid is the synthesis and storage of thyroglobulin.
The primary function of parafollicular cells in the thyroid is the synthesis and storage of thyroglobulin.
The thyroid gland originates from what embryonic structure?
The thyroid gland originates from what embryonic structure?
In response to TSH stimulation, thyroglobulin is transported to ______ where it is degraded for hormone release.
In response to TSH stimulation, thyroglobulin is transported to ______ where it is degraded for hormone release.
Match the following hormones with their roles in calcium regulation:
Match the following hormones with their roles in calcium regulation:
Flashcards
Cell-cell signaling
Cell-cell signaling
Communication between cells based on distance and chemical signals.
Hormone signaling
Hormone signaling
Hormones bind to surface or cytoplasmic receptors, triggering secondary messengers and cascades.
Homeostasis
Homeostasis
Maintaining stable internal conditions via regulatory mechanisms.
Negative feedback
Negative feedback
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Thyroid follicles
Thyroid follicles
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Follicular cells
Follicular cells
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Colloid
Colloid
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Parafollicular cells (C cells)
Parafollicular cells (C cells)
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Calcitonin
Calcitonin
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T3
T3
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T4
T4
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Thyroglobulin
Thyroglobulin
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Thyroid Peroxidase (TPO)
Thyroid Peroxidase (TPO)
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Graves' disease
Graves' disease
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Goiter
Goiter
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Hashimoto's thyroiditis
Hashimoto's thyroiditis
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Parathyroid Glands
Parathyroid Glands
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Parathyroid Cells
Parathyroid Cells
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Chief cells
Chief cells
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Parathyroid hormone (PTH)
Parathyroid hormone (PTH)
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Oxyphil cells
Oxyphil cells
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Hyperparathyroidism
Hyperparathyroidism
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Hypoparathyroidism
Hypoparathyroidism
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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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