Thyroid Hormone Physiology Flashcards

1
Q

What is the largest endocrine specific gland?

A
  • thyroid gland
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2
Q

What is the main function of the thyroid gland?

A
  • regulate basal metabolic rate
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3
Q

The thyroid is located below which important structure in the trachea and either side of what cartilaginous area?

A
  • larynx

- cricoid cartilage

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4
Q

Label the key parts of the thyroid gland using the labels below:

  • right thyroid lobe
  • left thyroid lobe
  • isthmus
A

1 - right thyroid lobe
2 - left thyroid lobe
3 - isthmus (connects left and right lobes)

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5
Q

What 2 muscles cover the thyroid gland?

A

1 - strap muscles

2 - sternocleidomastoid

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6
Q

What important chemical that must be consumed in the diet is required for thyroid hormone production?

A
  • iodine
  • recommended 150ug/day
  • contained within seafood, dairy products, seaweed, iodized salt, prunes, potatoes, lima beans
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7
Q

The thyroid is not a uniform structure, rather it is composed of follicles. Each follicle is composed of which type of epithelial cells?

A
  • cuboidal epithelial cells
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8
Q

The thyroid is not a uniform structure, rather it is composed of follicles. Each follicle is composed of cuboidal epithelial cells. What is the name of the area contained within the follicles that is surrounded by cuboidal epithelial cells?

A
  • colloid
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9
Q

The thyroid contains C cells. What do these cells secrete?

A
  • calcitonin

- regulate plasma calcium levels

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10
Q

Label the cross section of the thyroid gland using the labels below:

follicle
RBCs
capillary
C cells
colloid
cuboidal epithelial cells
A
1 - follicle
2 - capillary 
3 - C cell
4 - cuboidal epithelial cell
5 - RBCs
6 - colloid
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11
Q

Dietary iodine is ingested in food as I2 but is absorbed as what?

A
  • iodide
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12
Q

Which fascia is the thyroid gland enclosed by?

A
  • pretracheal fascia
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13
Q

In development the thyroid gland develops from the floor of what?

A
  • pharynx

- near the root of the tongue

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14
Q

Colloid is a substance that is contained within the follicles of the thyroid gland. What is the colloid substance composed of?

A
  • rich in thyroglobulin

- thyroglobulin is a large (660 kDa) tyrosine rich dimeric glycoprotein

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15
Q

Colloid is a substance that is contained within the follicles of the thyroid gland. The colloid substance is rich in thyroglobulin, a large (660 kDa) tyrosine rich dimeric glycoprotein. The thyroglobulin is produced by which 2 key organelles of the follicular cuboidal epithelial cells?

A
  • rough endoplasmic reticulum

- golgi

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16
Q

Thyroglobulin, the precursor for thyroid hormones and contains between 10-20 thyroid molecules that can be used to form thyroxine (T4) and triiodothyronine (T3). How is T4 and T3 formed from thyroglobulin?

A
  • iodine is bound to tyrosine residues of the thyroglobulin
  • iodine and tyrosine are then cleaved from the thyroglobulin forming T1 and T2
  • T1 and T2 can the be combined to create T4 and T3
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17
Q

The thyroid secretes thyroxine (T4) and triiodothyronine (T3). What % of T3 and T4 are secreted?

A
  • triiodothyronine (T3) =7%

- thyroxine (T4) = 93%

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18
Q

Triiodothyronine (T3) and thyroxine (T4) referred to as T3 and T4, why are they referred to as T3 and T4?

A
  • T refers to tyrosine
  • number relates to number of iodine molecules they have bound to tyrosine
  • T3 = 3 iodine molecules
  • T4 = 4 iodine molecules
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19
Q

Triiodothyronine (T3) and thyroxine (T4) are referred to as T3 and T4 because the T relates t tyrosine amino acid and the number relates to the number of iodine molecules bound to the tyrosine (T3 = 3 iodine molecules and T4 = 4 iodine molecules). Does T3 or T4 have a longer half life?

A
  • T4 has a longer half life

- T4 can be converted into T3 within cells

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20
Q

What are the 2 major extra-thyroidal organs that convert Thyroxine (T4) into triiodothyronine (T3)?

A

1 - liver

2 - kidney

21
Q

The 2 major extra-thyroidal organs that convert Thyroxine (T4) into triiodothyronine (T3) are the liver and the kidneys. What enzyme is response for converting T4 into T3?

A
  • iodothyronine de-iodinases

- can convert to active or inactive T3

22
Q

The 2 major extra-thyroidal organs that convert Thyroxine (T4) into triiodothyronine (T3) are the liver and the kidneys. Iodothyronine de-iodinases can convert T4 into the active T3. What are the 2 types of de-iodinases and where can they be found?

A
  • type 1 (D1) = liver, kidney, thyroid

- type 2 (D2) = muscle, brain, pituitary, skin and placenta

23
Q

The 2 major extra-thyroidal organs that convert Thyroxine (T4) into triiodothyronine (T3) are the liver and the kidneys. Iodothyronine de-iodinases can convert T4 into the active T3. There is a third type of Iodothyronine de-iodinases (D3) that does what to T4?

A
  • converts T4 into inactive form of T3

- a different molecule of iodine is removed to do this

24
Q

How is thyroglobulin created in the cuboidal epithelial cells and secreted into the colloid?

A
  • amino acid (tyrosine) and iodide are taken up by thyroid gland from blood
  • thyroglobulin is synthesised in rough endoplasmic reticulum
  • sugars added to thyroglobulin in golgi
  • thyroglobulin and peroxidase packed into vacuoles
  • endocytosis secretes vacuoles into colloid where iodine is added to the tyrosine molecules of the thyroglobulin
25
Q

Once thyroglobulin is created and secreted into the colloid, how is it then converted into thyroxine (T4) and triiodothyronine (T3) and secreted into the blood?

A
  • thyroglobulin broken down and endocytosed into the the cuboidal epithelial cells
  • colloid droplets of thyroglobulin merge with lysosomes
  • lysosomes proteolytic enzymes breakdown thyroglobulin into T3 and T4
  • T3 and T4 are then secreted into the blood
26
Q

What transporter is present on the basolateral membrane (closest to the blood vessels) of the thyroid follicular cells that allows iodide to enter the thyroid follicular cells?

A
  • Na+/iodide symtransporter
  • iodide molecule crosses with 2 Na+ molecules
  • N+ moves down concentration gradient
  • iodide- moves against concentration gradient as lots of iodide already in the cell
27
Q

What is present on the apical membrane (facing the colloid) thyroid follicular cells that is initially involved in transporting iodide into the colloid and the oxidation of iodide into something else?

A
  • pendrin an anion (negative charge ion) exchanged
  • exchanges iodide- for Cl-
  • involved in oxidising iodide into iodine in the colloid
28
Q

Pendrin is present on the apical membrane (facing the colloid) of the thyroid follicular cells and is initially involved in oxidation of iodide into iodine. What other enzyme is involved in the oxidation of iodide to iodine and the binding of iodine to thyroglobulin?

1 - iodothyropsine de-ionidase
2 - thyroid peroxidase
3 - peroxidase
4 - lipase

A

2 - thyroid peroxidase

facilitates the formation of T3 and T4 through combinations of monoiodotyrosine (MIT) and diiodotyrosine (DIT)

29
Q

What are the 4 things that can be created through the binding of tyrosine and iodine?

A

1 - monoiodotyrosine (MIT)
2 - diiodotyrosine (DIT)
3 - triiodothyronine (T3)
4 - thyroxine (T4)

30
Q

Na+/Iodide symtransporters are present on the basolateral membrane (closest to the blood vessels) of the thyroid follicular cells that allows iodide to enter the thyroid follicular cells. What other transporter is present on the basolateral membrane to facilitate iodide going against the concentration gradient?

A
  • Na+/K+ ATPase pump
  • Na+ moves out of the cell and into the blood
  • Na+ gradient allows Na+/iodide symtransporter to then function
31
Q

In the Chernobyl disaster there were large amounts of radiation in the form of iodine-131, which is a highly radioactive form of iodine. Iodine consumed in our normal diets is iodine-127, but the body is unable to tell the difference between the 2. Iodine is essential for creating thyroid hormones and is absorbed mostly by the thyroid. Why were people following the Chernobyl disaster given strong doses of K+/iodine?

A
  • a high dose of iodine-127 means the thyroid is full
  • blocks iodine-131 from being absorbed in the thyroid
  • reduces the risk fo thyroid cancer
32
Q

What does the hypothalamus and then pituitary gland secrete that then goes on to stimulate the thyroid gland?

A
  • hypothalamus = thyrotropin releasing hormone (TRH)

- pituitary gland = Thyroid-stimulating hormone (TSH) also known as thyrotropin

33
Q

There is a small network of blood vessels within the brain that connects the hypothalamus and the pituitary gland. What is this network of blood vessels called?

A
  • hypothalamic-hypophyseal portal system
34
Q

Once the thyroid gland has been stimulated to secrete thyroxine (T4) and triiodothyronine (T3) and the levels in the blood rise, how do T3 and T4 then regulate further secretion of T3 and T4 from the thyroid gland?

A
  • involved in negative feedback loop
  • T3 in tissues inhibits hypothalamus and pituitary glands stimulation
  • T4 in blood inhibits hypothalamus and pituitary glands stimulation
35
Q

Thyroid Stimulating Hormone (TSH) also known as thyrotropin is a glycoprotein produced by what?

A
  • thyrotrope cells of the anterior pituitary

- then goes on to stimulate the thyroid gland

36
Q

Thyroid Stimulating Hormone (TSH) also known as thyrotropin is a glycoprotein produced by the thyrotrope cells of the anterior pituitary, which then goes on to stimulate the thyroid gland. What type of cell receptor does TSH bind with on the thyroid gland?

A
  • GPCR

- specifically Gas

37
Q

Thyroid Stimulating Hormone (TSH) also known as thyrotropin is a glycoprotein produced by the thyrotrope cells of the anterior pituitary, which then goes on to stimulate the thyroid gland. TSH is able to bind with the GPCR Gas. What is the intracellular pathway of Gas?

A
  • GTP becomes GDP activating the alpha
  • GTP causes activation of adenyl cyclase (AC)
  • AC converts ATP to cAMP
  • cAMP a 2nd messenger molecule binds and activates protein kinase A
  • phosphorylation inside the cell occurs
38
Q

What effect can the cold have on the thyroid hormone stimulation?

A
  • lower temperature stimulates the hypothalamus to increase body temp
  • hypothalamus secretes more thyrotropin releasing hormone (TRH)
  • TRH stimulates the anterior pituitary which then secretes thyroid stimulation hormone (TSH)
  • TSH binds to thyroid and increases T4 and T3
  • increased T4 and T3 increase basal metabolic rate in an attempt to increase temperature
39
Q

What effect can fasting have on the thyroid hormone stimulation?

A
  • fasting causes reduced levels of leptin which inhibits hunger
  • less leptin means less stimulation of hypothalamus and thyrotropin releasing hormone (TRH) release
  • lower TRH means less stimulation of anterior pituitary gland and less thyroid stimulation hormone (TSH) release
  • less TSH means less stimulation of thyroid gland and less T4 and T3
  • less T4 and T3 means a reduction in the basal metabolic rate
40
Q

Thyroxine (T4) and triiodothyronine (T3) are amino acid hormones, that behave like steroid hormones, so they are hydrophobic and need to be bound to plasma proteins to move around in the blood. What are 3 examples of liver synthesised plasma proteins that can transport T3 and T4 in the blood?

A
  • thyroxine binding globulin (TBG)
  • thyroxine binding prealbumin or transthyretin (TTR)
  • albumin
41
Q

Thyroxine (T4) and triiodothyronine (T3) are amino acid hormones, that behave like steroid hormones, so they are hydrophobic and need to be bound to plasma proteins to move around in the blood. 3 examples of liver synthesised plasma proteins that can transport T3 and T4 in the blood are:

  • thyroxine binding globulin (TBG)
  • thyroxine binding prealbumin or transthyretin (TTR)
  • albumin

By binding to the these plasma proteins, does this increase or decrease their half life?

A
  • increases the half life, specifically T4 (lasts around 6 days)
  • T3 has a lower affinity for binding to plasma proteins
42
Q

Thyroxine (T4) and triiodothyronine (T3) are amino acid hormones, that behave like steroid hormones, so they are hydrophobic and need to be bound to plasma proteins to move around in the blood. 3 examples of liver synthesised plasma proteins that can transport T3 and T4 in the blood are:

  • thyroxine binding globulin (TBG)
  • thyroxine binding prealbumin or transthyretin (TTR)
  • albumin

How do T3 and T4 enter the cells?

A
  • via active membrane transport called monocarboxylate transporter 8 (MCT8)
  • a transporter protein for thyroid hormones
43
Q

Once thyroxine (T4) binds and enters the cells through MCT8, what is the first thing that happens to it?

A
  • converted into triiodothyronine (T3)

- converted by de-iodinase

44
Q

Once thyroxine (T4) binds and enters the cells through MCT8, it is converted into triiodothyronine (T3) by de-iodinase. T3 then has a high affinity to bind with what?

A
  • thyroid hormone receptors
45
Q

Once thyroxine (T4) binds and enters the cells through MCT8, it is converted into triiodothyronine (T3) by de-iodinase. T3 then has a high affinity to bind with thyroid hormone receptors. This then binds with what and enters the nucleus to act on DNA transcription?

A
  • retinoid X receptors (RXR)
46
Q

Once thyroxine (T4) binds and enters the cells through MCT8, it is converted into triiodothyronine (T3) by de-iodinase. T3 then has a high affinity to bind with thyroid hormone receptors (THR). This then binds with retinoid X receptors (RXR) inside the nucleus. What is the THR/RXR receptor complex then able to do?

A
  • bind with DNA, specifically the THR aspect of the THR/RXR complex
  • the part of th DNA the THR/RXR binds with is called the thyroid hormone response elements or hormone response elements (HREs)
  • binding to the HREs is able to modulates gene expression, transcription and protein synthesis
47
Q

The figure below shows the basal metabolic rate following an injection of thyroxine (T4) and the following de-iodination by iodothyronine deiodinase enzyme creating triiodothyronine (T3). How does this explain the curve observe in the figure below in relation to basal metabolic rate (BMR)?

A
  • low BMR initially as the T4 has not undergone de-iodination by iodothyronine deiodinase enzyme
  • as T4 begins to undergo de-iodination the levels of T3 increase as does BMR
48
Q

What is the normal secretion levels of thyroxine (T4) and triiodothyronine (T3) by the thyroid gland?

A
  • T4 = 100ug

- T3 = 35ug