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Therapeutics of thyroid disease Flashcards

1
Q

what cells secrete T3 and T4

A

Thyroid follicular cells

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2
Q

where is the thyroid gland? what does it consist of?

A

in front of the trachea

2 lobes

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3
Q

TF: some people have a third lobe?

A

TRUE

10-30%

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4
Q

if someone has a third thyroid lobe what is it called?

A

pyramidal

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5
Q

what are the functional units of thyroid cells?

A

thyroid follicles which are filled with thyroglobulin

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6
Q

what is the point of thyroglobulin?

A

acts as a store of iodide

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7
Q

how long can thyroglobulin supply thyroid hormones for?

A

90 days

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8
Q

what are parafollicular C cells?

A

in between the follicles

for calcitonin production

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9
Q

what happens when the body gets cold- in relation to the thyroid

A

thyrotropin releasing hormone from the hypothalamus

this causes the anterior pituitary to release TSH
TSH goes to the thyroid gland and triggers T3 and T4 release

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10
Q

T__ does negative feedback. explain?

A

3
to the anterior pituitary to reduce the amount of TSH secreted
AND
longer loop feedback to reduce TRH secreted from the hypothalamus

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11
Q

explain how low T3 concentrations increase the thyroid gland

A

Low T3 concentrations- likely we also have low signal of TRH from hypothalamus
Pituitary Thyrotropes will then increase the amount of TSH which will then increase amount of thyroid hormone secreted
This causes the enlargement of thyroid cells to increase amount of thyroid hormones

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12
Q

explain how high T3 concentrations causes thyroid regression?

A

High T3- TRH from hypothalamus will be low, will cause Pituitary thyrotropes to reduce TSH production (a and b subunits= of the TSH protein)
The production of TSH hormone will be low
This reduces thyroid gland activity.
Decrease in size of the thyroid gland

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13
Q

the TSH receptors are located on?

A

thyroid follicular cells

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14
Q

the TSHR is a ______ receptor.

how does this work?

A

GPCR

which activates adenylate cyclase to produce the intracellular messenger cyclic AMP

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15
Q

cAMP activates what In the cell

A

all functional aspects of the cell

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16
Q

what 4 things does cAMP do to the thyroid cells

A
  1. Thyroglobulin synthesis- colloid in the center of each of these follicles
  2. Iodide pumping into the thyroid follicular cells and follicular lumen;
  3. Iodination by thyroid peroxidase;
  4. Endocytosis, proteolysis and hormone release
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17
Q

how is iodide from the diet transported into the follicular lumen?

A

from the blood
over the basolateral membrane into the follicle via Na/Iodide symporter which is in conjunction with the Na/K ATPase pump

then across the apical membrane into the lumen via Pendrin transporter for I and CL ions

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18
Q

what transporter brings iodide over the basolateral membrane from the blood stream?

A

Na/K pump in conjunction with Sodium/ iodide symporter (NIS)

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19
Q

What transporter transports Iodide over the apical membrane?

A

Pedrin for I and Cl ions

exchanger

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20
Q

how many Na ions and I- ions are bought across the basolateral membrane at one time?

A

2 Na for each 1 I-

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21
Q

what happens to the iodide once it enters the lumen?

A

oxidised to atomic iodine.

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22
Q

where is thyroglobulin produced? where does it end up?

A

thyroid follicular cells

released by exocytosis into the lumen

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23
Q

where is the thyroid peroxidase enzyme complex located?

A

spans the apical membrane

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24
Q

what does the thyroid peroxidase enzyme complex do?

A

it adds iodide onto tyrosine residues on the thyroglobulin backbone

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25
how many places on the tyrosine residue can iodine be added onto?
2- either side of the OH
26
how is iodine bound to the tyrosine residues
covalently
27
what two things can be made when the iodine is bound to the tyrosine residues?
mono-iodotyrosine | Di-iodotyrosine
28
when is Di-i made?
when 2 iodine molecules are added to the backbone
29
what does the addition of either one or 2 iodines effect?
wether T3 or T4 is produced
30
what enzyme conjugates 2 tyrosines together?
Tyrosine peroxidase enzyme
31
TF: tyrosine peroxidase enzyme can conjugate more than 2 tyrosine molecules together
FALSE- always 2
32
how do you get T3?
if you conjugate a DIT with a MIT
33
How do you get T4?
if you conjugate DIT and DIT
34
what bond is formed when you conjugate 2 tyrosine molecules?
ester
35
where does iodation and conjugation via TPO occur?
in the thyroid follicular lumen
36
what happens to the iodinated thyroglobulin once its formed?
moves back into the cells by endocytosis
37
what happens to the conjugated iodinated tyrosine residues once they're back in the cells
T3 and T4 is cleaved from thyroglobulin and released by the cells into the bloodstream
38
how are the conjugated, iodinated tyrosine residues cleaved from thyroglobulin
proteolysis by lysosomes
39
what happens to the thyroglobulin and iodide once this process is complete?
recycled
40
what is the major form of thyronine hormone in the blood?
T4- thyroxine
41
T4 has a _____ half life then T3?
LONGER
42
T4 is ______ potent than T3?
less
43
TF: T4 can be converted into T3?
true
44
is reverse T3 secreted alot?
no less than 1%
45
what is reverse T3?
MIT is reversed
46
if levels of T4 are too high, what will the body do?
convert it to rT3
47
Levothyroxine sodium treats?
hypothyroidism
48
liothyronine sodium treats?
hypothyroidism
49
what does levothyroxine sodium contain?
thyroxine T4
50
what does liothyronine sodium contain?
T3
51
drug treatments for hyperthyroidism? mechanism of action?
block synthesis of thyronine hormones Carbimazole tablets propylthiouracil tablets
52
T4 is hydro____. therefore ______ in serum
phobic | insoluble
53
why can liver disease lead to loss of effective T4 transport?
as the liver makes the binding proteins needed to transport hydrophobic T4 in the blood
54
what is the most important thyroid hormone binding protein?
TBG- thyroxine- binding globulin
55
what binding protein delivers most thyroid hormones to the brain?
transthyretin (TTR)
56
transthyretin binds ___% of T4
20
57
Thyroxine binding globulin binds ___% T4. AND prevents its loss in...
70-75 | urine
58
TF: transthyretin binds T3 and T4
false only T4
59
What is the ratio of : | protein bound T4:T3
20:1
60
albumin binds __% T3 and ___% T4
30 | 10
61
examples of transporters which allows T3 and T4 to enter cells?
OATP1c1 MCT8 MCT10
62
T_ is biologically active
3
63
what must happen to T4?
be converted to T3
64
what converts T4 into T3?
INTRACELLULAR iodothronine deiodinases- iodine removed
65
where are iodothronine deiodinases (DIOs) located
intracellularly
66
what does the enzyme iodothronine deiodinases (DIOs) contain?
seleno-cysteine
67
how does the selene-cysteine in the iodothronine deiodinases convert T4 into T3?
selenium accepts iodide
68
how many types of DOI's are there?
3
69
which types of DIOs make T3?
DIO1 or DIO2
70
which types of DIOs make rT3?
DIO1 and DIO3
71
What is DIO1 important for?
circulating t3
72
Where does DIO1 predominate?
``` the liver kidney muscle all good blood supply! thyroid ```
73
DIO1 produces most of the _____ T3. NOT _____ T3.
INTRACELLULAR | circulating
74
DIO2 is important for?
converting intracellular T4 into T3
75
Where does DIO2 predominate?
CNS pituitary thyrotropes skeletal muscles sometimes
76
DIO2 controles?
intracellular T3 levels
77
what is DIO2 important for?
feedback regulation
78
what does DIO3 produce?
rT3
79
why is DIO3 important?
prevents thyroid hormone reaching specific tissues e.g. pregnancy
80
what happens to DIO3 when you produce too much thyroid hormone?
it increases to protect from thyroid overload
81
thyroid hormone receptors are _____ receptors
nuclear TRa TRb
82
how do thyroid hormone receptors exist?
as heterodimer with retinoid X receptors (RXR) | transcription factors
83
how do thyroid hormone receptors in the nucleus work when thyroid hormone isn't present?
bind to Thyroid response element (TRE) of the gene if thyroid hormone ISNT present, it blocks transcription by recruiting repressors and preventing transcription for that gene?
84
what happens when thyroid hormone binds to receptors in the nucleus?
the repressors will leave and the gene will be transcribed and a protein will be produced
85
TR have a ____ fold affinity for T3 than T4
15
86
TF: thyroid hormone binding ONLY increases transcription.
FALSE | can inhibit- depends on the cell type
87
what regulates intracellular supplies of T3 to the nucleus of T3 target cells?
``` MCT8 MCT 10 OATP1C1 DIO2, 3 T4 rT3 ```
88
In the anterior pituitary gland T3 binding has a _____ effect on transcription
promoting
89
what happens in the anterior pituitary when T3 binds?
increase in growth hormone produced
90
T3 ____ prolactin production
decreases
91
T3 ______ alpha and beta subunits of TSH
decreases
92
why does T3 reduce the amount of prolactin and alpha and beta subunits of TSH?
as if there's a high amount of T3, you dont need any more | so by decreasing these, no more T3 will be produced
93
TF: T4 conversion to T3 only happens intracellularly
FALSE | intra or extra
94
biological actions of thyroid hormones?
``` metabolic rate control growth foetal development CV effects muscoskeletal effects ```
95
how does T3 control basal metabolic rate?
In this case the T3 increases transcription: you will increase the NA/K ATPase pump proteins, mitochondrial resp enzymes, other enzymes and proteins for tissue growth and maturation If you increase the MRE then you will have a higher oxygen consumption, so effects the heart to pump more blood, also effects ventilation to increase delivery of oxygen Increased ventilation also needed to rid body of CO2 Increased metabolic rate: Muscle mass and adipose will decrease as need the nutrients released from their breakdown Increased body temperature- other mechanisms needed to bring this down
96
what can deficiencies in thyroid hormones lead to?
abnormal growth, development, reproduction, behaviour and metabolism effects all organs throughout life
97
role of thyroid hormone in foetal development?
developing neural and skeletal systems
98
loss of T4 supply to a foetus leads to irreversible....
mental impairment and dwarfism
99
what is this lack of T4 supply to a foetus known as?
congenital iodine deficiency syndrome- mental impairment and dwarfism
100
if thyodide hormones are disrupted in the foetus what can happen?
stillbirths miscarriage congenital morbidity and mortality congenital iodine deficiency syndrome
101
if thyroid hormones are disrupted in a neonate what can occur?
neonatal goiter neonatal hypothyroidism impaired mental function
102
if thyroid hormones are disrupted in childhood and adolescent?
loiter- swelling round the neck hypothyroidism impaired mental function impaired physical function
103
metamorphosis requires....
thyroid hormones | in other species obviously
104
overall cardiovascular effects of T3?
``` increases: cardiac contraction and output heart rate oxygen supply to tissues CO2 removal from tissues ```
105
physiological effects on cardiovascular function of T3?
increased: myocardial Ca2+ uptake expression of a-myosin heavy chain and DECREASED expression of b expression of Ryan-dine receptor in SR
106
T3 causes vaso____
dilation | bring body temperature down
107
T3 _____ sensitivity to catecholamines?
INCREASES
108
T3 bone turnover effects?
stimulatory effect increasing formation and resorption
109
T3 effect on linear bone growth?
increases after birth
110
T3 _____ rate of muscle relaxation?
INCREASES
111
muscoskeletal effects when you have hypo or hyperthyroidism?
muscle tremors and weakness

Patient (19 decks)

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