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Y3 Patient Sem 1 > The Thyroid Hormone and Gland > Flashcards

The Thyroid Hormone and Gland Flashcards

1
Q

what is the structure of the thyroid gland?

A

situated infront of the trachea, just below the adams apples.
consists of 2 lobes (right and left), but 10% of people have a 3rd lobe

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2
Q

whatis the 3rd lobe called?

A

pyramidal lobe - this doesn’t effect how the thyroid gland works

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3
Q

what does the thyroid follicular cell secrete?

A

T3 and T4

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4
Q

what are the functional units within the thyroid gland/

A

the follicles - these are filled with thryoglobulin

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5
Q

what does thryoglobulin contain?

A

sufficient iodine to supply the thyroid for 90 days

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6
Q

why is iodine needed within the thyroid?

A

it is critical for the thryoid function as it makes the thyroid hormone

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7
Q

how does thyroid gland produce thyroid hormone?

A

as an interaction between the thryoid follicular cells and the colloid

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8
Q

what is the function of parafollicular C cells?

A

they are in between the follicles and are responsible for the secretion of calcitionin - which is needed for calcium homeostasis.

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9
Q

how is thyroid gland function regulated?

A

the endocrine organs work through an axis.
when a change in environment is detected by neurones in the hypothalmus - the body will repsond by secreting TRH which travels to the anterior pituitary gland.
this then stimulates TSH which works on the thyroid gland and triggers the release of T3 andT4.

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10
Q

what is TRH?

A

thyrotropin releasing hormone

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11
Q

what is TSH?

A

thyroid stimulating hormones

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12
Q

which is more important t3 or t4?

A

T3 is most important within the body as it has a feedback effect to reduce the amount of TSH produced and TRH.

but t4 is produced in a much greater quantity.

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13
Q

what happens if we have a low t3?

A

it is likely you will also be having a low TRH from the hypothalmus. this means you need to increase TSH that is secreted to try and improve the amount of thyroid hormone produced. this means you have a thyroid enlargement and increased activity to try and increase the amount of TRH.

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14
Q

how does TSH stimulate thyroid follicular cells to produce t3 and t4?

A

the thyroid follicular cells have cell surface receptors for TSH, which is a g protein coupled receptor. this means when it binds it activates adenylate cyclase to produce intracellular messenger cAMP.

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15
Q

what does cAMP activate do?

A
  1. thryoglobulin synthesis - colloid centre of the follicles
  2. iodide pumping - into the follicular cells and lumen
  3. iodination by thyroid peroxidase
  4. endocytosis, proteolysis and hormone release
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16
Q

where does iodide come from in humans/

A

diet - imn the blood but neede to get it through the baolateral cell membrane

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17
Q

what is the basolateral memrbane>

A

this is the membrane of the thyroid follicle cell that is facing the blood

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18
Q

how is iodide transported into follicular cells?

A

transporter on the basolateral side is the sodium/iodide transporter which brings iodide ions to the thyroid follicular cells.
this is used in conjunction with Na/K/ATPase as it requires energy.
you need to maintain the sodium gradient to aid the transport of iodide into the cell

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19
Q

which transporter allows iodide to move into the follicle itself?

A

the pendrin transporter

which is found in a number of different cells

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20
Q

how is thyroglobulin produced in the follicular cell?

A

need to travel from basolateral to apical. this isfrom the blood to the thyroid follicle lumen. as thyroglobulin is produced in the follicle cells and is then released by exocytosis into the thryoid lumen

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21
Q

how are the iodothyronines formed and coupled in the thyroglobulin molecule?

A

TPO enzyme complex situatied in membrane near the lumen adds iodide to the thyroglobulin backbone of tyrosine molecules.
this spans the apical membrane
not only does it ADD iodine but it also CONJUGATES the two tyrosine molecules together

22
Q

what is TPO?

A

thyroid peroxidase

23
Q

what does 2 DIT produce?

A

t4 produced

24
Q

what does it mean if you have a DIT with a MIT?

A

t3 produced

25
Q

what is t4 name?

A

tetraiodothyronine

26
Q

what is t3 name?

A

triiodothyronine

27
Q

how does it undergo apical to basolateral transportation/

A

the huge complex of the iodinated backbone will be taken into the cell by endocytosis.
once it is in the cell it will be subjected to proteolysis by the lysosomes and this will release either t3 or t4 from the backbone.
any leftovers will be recyled to produce the hormones

28
Q

which thryonine hormone has a longer half life/

A

t4

but t3 is more potent and active and t4 can be converted into t3 whenever it is required

29
Q

what is the other type of thryonine hormone?

A

reverse t3
this is inactive and less than 1% is secreted in the boyd.
the MIT is in a different position. t4 will be converted into reverse t3 to protect to body

30
Q

when would you use t3 and t4 in treatment?

A

for hypothyroidism
t4 = levothyroxine sodium
t3 = liothyronine sodium

31
Q

when would you use anti-thryoid drugs?

A

for hyperthyroidism

  • carbimazole
  • propylthiouracil
32
Q

how is t4 transported in serum?

A

T4 is hydrophobic so therefore insoluble in serum.

This means you need to have it transported with specific binding proteins which will be synthesised by the liver

33
Q

what will liver disease lead to?

A

it can lead to the loss of effective t4 transport to peripheral tissues - affecting thyroid function

34
Q

what are the 3 thyroid hormone binding proteins?

A
  • thyroxine binding globulin (TBG)
  • transthyretin (TTR)
  • albumin
35
Q

what is TBG?

A
  • Binds 70-75% of plasma T4
  • Large circulating reservoir of T4
  • Prevents loss in urine – as it is bound to the proteins. Keeps the hormones within the bloodstreams
36
Q

what is TTR?

A
  • Binds 20% of plasma T4

* Important for the delivery to the CNS

37
Q

what is albumin?

A
  • Binds 5-10% of plasma T4

* Ubiquitous binding protein

38
Q

what is the binding specifcity of the thryoid hormone binding proteins and their half lives?

A
  • TBG binds to both T4 and T3; half life = 5 days
  • Transthyrtetin binds to T4 only; half life = 2-3 days
  • Albumin binds T3 (30%) and T4 (10%)
39
Q

how is t3 and t4 transported into cells?

A
  • bound t3 and t4 cannot enter cells
  • free t3 and t4 can enter cells via specific transporters (MCT8, MCT10, OATP1c1)
  • t3 is biologically active
  • t4 is relatively inactive and will be converted to t3 by intracellular idothryonine deiodinases
40
Q

how do iodothyronine deiodinases work?

A

selenium accepts the iodide from the t4 to make it a t3.

DIO 1 and DIO 2 are the most active and will make t3 by removing the correct iodide.

41
Q

what is iodothronine deiodinase 1 (DIO1)?

A
  • predominates in liver, kidney and muscle -> due to them having greatest blood supply
  • also found in thyroid
  • produces MOST of the circulating T3 - not intracelluar producing it on the outside of the cell
42
Q

what is Iodothryonine deiodinase 2 (DIO2)?

A
  • predominates in the areas of the CNS and pituitary thryotropes
  • controls intracellular t3 concentration
  • important for feedback regulation
  • found in skeletal muscle in some species
43
Q

what is Iodothryonine deiodinase 3 (DIO3)?

A
  • produces inactive T3
  • prevents thyroid hormones acces to specific tissues - especially during pregnancy
  • if you have too much thyroid hormone you might take DIO3 to reduce these levels.
44
Q

what is the thyroid hormone action?

A

there are thyroid hormone receptors either TRa or TRb (alpha and beta)
they are found in the nucleus, and heterodimer with retinoid X receptors.
• Binds to TRE
• 15-fold increase of affinity for T3 than T4
• Increased gene transcription
• Can also inhibit gene transcription!
• Stop the part of the gene being transcribed and acts as a transcriptions blocker
• When thyroid hormone binds to the receptor it releases the block so they will go away and the gene will be transcribed and a protein produced

45
Q

what are the 5 biological actions of thryoid hormones?

A
  1. Control of metabolic rate
  2. Growth
  3. Foetal development
  4. Cardiovascular effects
  5. Musculoskeletal effects
46
Q

how does it control basal metabolic rate?

A

receptors change the gene transcription to increase basal metabolic rate.
if you increase metabolic rate you will have to increase other things to be able to adapt.
need to increase oxygen consumption within the boyd, so the body needs to supply more oxygen - this means tou need to have an effect on the heart to circulate the oxygen around the body.
this also means you need to increase ventilation so you can remove the co2 - and you need treduce muscle mass as nutritents will be released from their tissues to increase metabolic rate

47
Q

how do thyroid hormones have growth regulating roles?

A
  • most bodily functions are affected
  • often synergise with other hormones
  • defeiences lead to abnormal growth, development, reproduction and metabolims
  • exerts effects on all organs and tissues throughout life
48
Q

what is the role of thyroid hormones in foetal development?

A
  • KEY ROLE IN DEVELOPING NEURAL AND SKELETAL SYSTEMS
  • loss of T4 supply to foetus leads to irreverisble mental impairment and dwarfism = cogenital iodine defiecny syndrome
  • it is essential for normal growth of the feutus
  • this happens if the iodide supply was disrupted or not availlable in eqaul amounts
49
Q

what does T3 increase in the heart?

A
  • cardiac contraction and output
  • heart rate
  • oxygen supply to tissues
  • co2 removal from tissues
50
Q

what is the direct effect of the thyroid hormones on the heart?

A
  • increased myocardial Ca2+ uptake
  • increased expression of alpha-myosin heavy chain and decrease beta-myosin
  • increased expression of RYR in SR (calcium channel)
51
Q

what are the indirect effects of thyroid hormones on the heart?

A
  • increased metabolisum, thermogenesis and vasodilation
  • increased sensitivity to catecholamines
  • need to bring back temperature to cool body back down
52
Q

what are the muscoskeletal effects of thyroid hormones?

A
  • T3 has a potent stimulatory effect on bone turnover - increases both formartion and resorption
  • T3 increases linear bone growth after birth
  • T3 increases the rate of muscle relaxtion - but it can lead to tremors
  • for normal skeletal muscel function you require T3

Y3 Patient Sem 1 (20 decks)

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