Lecture 22-thyroid gland Flashcards

1
Q

Structure of thyroid gland

A

1•THYROID FOLLICLES (the big pinkish things)
2•FOLLICULAR CELLS (the darker pink cells which surround them)
3•COLLOID (light pink stuff at the centre of the thyroid follicles – full of THYROGLOBULIN
4•CAPILLARIES
5•CAPSULES OF CONNECTIVE TISSUE
6•‘C’ CELLS

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2
Q

T3 is

A

Triiodothyronine
=10% TH secretion
=most potent
inactive form = rT3 = 0.9% secretion, increases with stress

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3
Q

rT3 is

A

Reverse T3 (triiodothyronine)
=0.9% secretion
=inactive form
=iodine removed from inner ring rather than outer ring as in T3

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4
Q

T4 is

A

Thyroxine
=90% secretion
=less potent form
=converts to T3 inside cells

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5
Q

Which is most potent thyroid hormone?

A

T3

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6
Q

Which is most synthesised thyroid hormone?

A

T4

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7
Q

What increases the production of rT3?

A

Stress

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8
Q

What % of thyroid hormone = T3

A

10%

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9
Q

What % of thyroid hormone = T4?

A

90%

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10
Q

What % of thyroid hormone = rT3

A

0.9%

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11
Q

What is the difference between T3 and rT3

A

in rT3 iodine is removed from the inner ring, rather than the outer ring (As in T3) therefore it is biologically inactive.

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12
Q

We absorb iodine as?

A

Iodide (I-)

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13
Q

what is the recommended dietary requirement for iodine?

A

1mg/week

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14
Q

How do we store iodine?

A

With an IODIDE PUMP in the follicular cells

20-50xs higher Iodide concentration inside cell than in the plasma

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15
Q

What are the main ingredients for TH?

A

(1) Iodide (I-)

2) Thyroglobulin (Thyroglobin precursor) (produce in follicular cells

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16
Q

What are the 6 stages of thyroid hormone synthesis?

A

(1) IODIDE TRAPPING (bringing iodide into follicular cells)
(2) SYNTHESIS OF THYROGLOBULIN (Synth in ER; modified in Golgi; transported in vesicles to apical surface; exocytosed to colloid)
(3) OXIDATION OF IODIDE–>IODINE (by enzymes in colloid)
(4) IODINATION OF TYROSINE (residue on thyroglobulin molecule; iodine binds tyrosine on thryoglobulin ==> DIT or MIT)
(5) Coupling tyrosine residues (MIT+DIT=T3; DIT + DIT=T4)
(6) PINOCYTOSIS & DIGESTION OF COLLOID (back into follicular cell; digestion after fusing with a lysosome which cleaves T3/T4 and uncoupled DIT/MITs)

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17
Q

Thyroglobulin

A

precursor for thyroglobin

contains the amino acids TYROSINE

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18
Q

DIT

A

DIiodothyronins (Tg+ two I-)

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19
Q

MIT

A

MONOiodothyronins (Tg+ one I-)

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20
Q

What moves iodide into the follicular cell?

A

Sodium-Iodide symporter (pump that transports iodide across the membrane into the follicular cell)

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21
Q

What moves iodide from the thyroid follicular cell into the colloid?

A

Iodide-Chloride antiporter

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22
Q

What is formed with the iodine & thyroglobulin bind together in the colloid?

A

Either DITs or MITs (di-iodo-thryonins or mono-iodio-thyronins)

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23
Q

DIT + MIT =

A

T3

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24
Q

DIT + DIT

A

T4

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25
What transports TH?
THYROXINE BINDING GLOBULIN (TBG) = specific transporter to which TH preferentially binds (>99% binds) Can also bind to albumin but mainly TBG
26
Conversion of T__ to T__ inside cells
By interactions with DEIODINASES T4=deoiodinases=>T3
27
DEIODINASES
Convert T4==>T3 (most potent) within target cells...so in thinned most of the TH is actually T3 although T4 is mainly secreted)
28
TH processing within cells
1. Separates from TBG (in blood) 2. Diffuses into cells 3. Interacts with deiodinases (converts T4-->T3) 4. binds to NUCLEAR RECEPTOR =changes transcription/translation to increase protein synthesis & various cell specific metabolic effects.
29
What does TH do once in the cell?
Binds to nuclear receptors which changes the transcription and translation of the cell
30
What is the mechanism of release of TH?
TRH tonic basal release from hypothalamus => Acts on TSH in the anterior pituitary => ++ feedback on thyroid gland to produce TH ==> -tive feedback on AP and hypothalamus
31
What are the effects of TH on BMR?
1•++ basal metabolic rate 2•++# and size of the mitochondria (60-100%) 3•++ATP production 4•++VO2 5•++active transport of ion across membranes
32
What is the normal rate of release of TH per day?
100µG
33
TRH
¬ Thyroid releasing hormone (secreted by hypothalamus onto the anterior pituitary) (tonic basal release)
34
TSH
¬ Thyroid stimulating hormone (secreted by anterior pituitary onto thyroid)
35
T3/T4:
¬ Thyroid hormones (secreted by thyroid), Have negative feedback on pituitary & hypothalamus.
36
EFFECTS OF TSH ON THYROID:
1. + TH synthesis 2. + TH secretion 3. + Size of gland 4. + Blood flow to thyroid
37
EFFECTS OF TH ON TARGET CELLS
1. + BMR (+60-100%) 2. + ATP production 3. + # & size mitochondria 4. + VO2 (O2 consumption increased) 5. + Active transport of ions across membrane
38
EFFECTS OF TH ON CHO METABOLISM
1. + glucose absorption (in GIT & uptake into cells) 2. + glucose oxidation (mainly in liver, fat & muscle) 3. + gluconeogenesis (more glucose formed from non-CHO sources) 4. + insulin secretion (to facilitate + glucose uptake)
39
EFFECTS OF TH ON LIPID METABOLISM
1. + Lipolysis 2. + Lipogenesis 3. NET = + [FFA], -- TG + cholesterol in blood
40
EFFECTS OF TH ON PROTEIN METABOLISM
1. Synthesis | 2. Degradation
41
What are the THERMOGENIC EFFECTS of TH?
1- b/c TH ++ BMR 2-by-product of ATP production is heat 3-Remove thyroid = reduced ability to thermoregulate 4-Infants/adults in arctic have ++ TH in circulation
42
Effect of TH on GROWTH AND MATURATION in the SKELETAL SYSTEM
o ++ bone formation => acts synergistically with other growth factors o Involved in bone maturation (maybe), including closure of epiphyses
43
Effect of TH on GROWTH AND MATURATION in the CNS
o Mental state: ♣ Hypothyroid= sluggish ♣ Hyperthyroid= anxious o Essential for normal brain development
44
Effect of TH on GROWTH AND MATURATION in the CARDIOVASCULAR SYSTEM
1 o + stimulation of sinoatrial node => 2 o + heart rate & contractility=> 3 o + cardiac output => 4 o + tissue blood flow * Increased tissue blood flow * Increased cardiac output * Increased heart rate * Increased contractility
45
What is the effect of HYPOTHYROIDism on mental state?
♣ Hypothyroid= sluggish
46
What is the effect of HYPERTHYROIDism on mental state?
♣ Hyperthyroid= anxious
47
The 5 CAUSES of HYPOthyroidism (in adults)
(1) HASHIMOTO'S THYROIDITIS (autoimmune disease where thymocytes are destroyed = reduced TH production/secretion) (2) REDUCED levels of TSH (pit-1 deficiency) (3) REDUCED TRH (4) Post-ablative hypothyroidism: (5) Dietary iodine deficiency
48
What is POST ABLATIVE HYPOTHYROIDISM
People with hypERthyroidism then treated with radioactive iodine = destroys too many cells=> hypOthyroidism
49
What is the most common cause for HYPOTHYROIDISM?
Dietary iodine deficiency - Long term deficiency (remember substantial stores in cells, takes a while to deplete). - Without iodine cannot synthesise functional TH
50
What are the effects of TH on metabolism?
1• Increased lipid metabolism: lipolysis and lipogenesis 2• Rapid mobilization of lipids from fat tissue 3• Increased free fatty acids and degreased triglycerides In terms of protein metabolism, increased synthesis but also increased breakdown (degredation).
51
What is the effect of the thyroid on temperature regulation?
1•Increased BMR increases thermogenic effect | 2• Increased thyroid in cold conditions
52
How does TH affect protein metabolism?
Increased protein synthesis and increased degradation
53
What are the effects of TH on the bone?
Increases rate of growth of bone and plays a role in bone maturation (closing of the epiphyses)
54
What is involved with Hashimotos thyroiditis?
Thyrocyte destruction
55
What does hashimoros cause?
Decreased levels of TSH or TRH, caused by post-ablative hypothyroidism
56
What are the side effects of hypothyroidism?
``` 1•Lack of energy 2•++ body weight 3•MYXEDEMA connective tissue in subcutaneous skin leading to oedema 4•Decreased sensory and memory capacity 5•Poor tolerance of cold 6•Goiter ```
57
MYXEDEMA
connective tissue in subcutaneous skin leading to oedema
58
What are the consequences of iodine deificency in developing children?
1•Severe irreversible mental and physical retardation 2•Short stature 3•Bone age retardation 4•Malformation of facial bones
59
What causes hyperthyroidism?
* GRAVES DISEASE | * TUMOURS that secrete TH. Treated by surgical removal
60
GRAVES DISEASE
Antibodies (igGs) that bind and activate the TSH receptors=> ++TSH => ++TH production Treated with drugs
61
What is characteristic of hyperthyroidism?
Low TRH and TSH and high T3 and T4
62
What are the symptoms of hyperthyroidism?
1•++ metabolic rate & heat production 2•++protein degradation 3•++fatty acid metabolism 4•Exaggeration of autonomic responses 5•Hyper-excitability and restlessness 6•EXOPTHALMOS (pressure behind the eyes)
63
EXOPTHALMOS
Fatty deposits on ocular muscle + fluid accumulation behind eye balls (pushes eyeballs forward)
64
GOITROGEN (PTU)
Analogous to iodine deficiency | Low levels of T3 and T4, absence of negative feedback means high TSH & TRH
65
THYROXINE
Added dose of TH = ++T4 | => negative feedback to hypothalamus + anterior pituitary = reduced TRH & TSH