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Pharm Year 3 Sem1 patient > patient sem 1 : Thyroid > Flashcards

patient sem 1 : Thyroid Flashcards

1
Q

where is the thyroid gland?

A

the thyroid gland is found infront of the trachea and Adams apple

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2
Q

how many lobes does the thyroid have ?

A

2: left and the right , some people (10-30%) have a 3rds lobe - the pyramidal lobe

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3
Q

Describe the microscopic structure of the thyroid gland

A

functional units : thyroid follicles
each follicle is full of thyroid globulin which is an iodide store (essential for gland functioned for thyroid hormone)
follicles also contain follicular cells on the perimeter
and colloid glycoprotein in the centre
parafollicular C cells between the cells

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4
Q

what is the function of a parofollicular c cell?

A

production and secretion of calcitonin ( responsible for calcium homeostasis)

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5
Q

How is the thyroid gland regulated?

A

hypothalamus releases TRH
ant. pituitary releases TSH
thyroid gland releases Thyroid hormones (T3 and T4)

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6
Q

describe the differences between t3 and t4 (thyronine hormones)

A 
t3 is more active
t3 is secreted in a smaller quantity
t3 has 3 iodide molecules ,t4 has 4 
t3 is invoelt in negative feedback loop for HPT axis
t3 has a shorter half life
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7
Q

what happens when there is a low body temperature

A

hypothalamus detects low body temperature, triggers release of thyroid hormone via HPT axis, leads to an increase in basal metabolic rate, heat generated
homeostasis achieved.
negative feedback brings thyroid hormone back to normal

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8
Q

describe the effects of low t3 on thyroid gland

A

if there are low levels of T3, likely low TRH , stimulates pituitary thyrotropes increasing TSH levels,TSH causes enlargement of thyroid via follicular cells overactivity

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9
Q

describe the effects of high t3 on thyroid gland

A

if there are high levels of T3, TRH will be low, high T3 cause thyrotropes to reduce TSH production, , reduces thyroid gland activity, less hormone produces, decreased size

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10
Q

describe how TSH has an effect on the thyroid

A

TSH in blood stimulates follicular cells to produce thyronine hormones

follicular cells have cell surface receptors for TSH
(gPCR)
activates adenylate cyclase to produce cAMP

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11
Q

name 4 functions of the thyroid cells

A

thyroglobulin synthesis

iodide pumping into follicular cells and follicular men

iodination by thyroid peroxidase

endocytosis,proteolysis and hormone release

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12
Q

What is thyroglobulin? where is it found

A

(backbone of thyronine synthesis), found in centre of follicles

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13
Q

how does iodide enter the follicular cells?

A

transported into basolateral cell membrane via sodium/iodide symporters (NIS) (is a co transporter)
co- transports NA and I- to maintain Na+ gradient which powers iodide movement
gradient maintained by Na/K+ ATPase transporter to actively transport Na out to maintain gradient

then over apical membrane into lumen via the Pendrin transporter : an ionexchanfer (cl- and iodide -) found in many body cells

once in cell, iodide oxidised to iodine

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14
Q

how is thyroglobulin produced?

A

produced by the endoplasmic reticulum in the follicular cells nd exocytosed into thyroid lumen

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15
Q

how are iodotryrosines formed and coupled in the thyroglobulin molecules

A

TPO adds iodide onto the backbone
addition occurs either side of the Oh molecules, max 2 iodide per backbone
backbones can join together (conjugate) tp produce t3 (3 iodides) or t4 (hormones)

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16
Q

what does DIT and MIT mean?

A

di- iodotryosine

mono-iodotyrosine

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17
Q

ROLE OF TPO?

A

addition of iodide to thyorogobulin backbone

conjugation and DIT and MIT

18
Q

How are T3 and t4 formed

A

DIT + DIT = T4

MIT + DIT = T3

19
Q

describe the release of T3 and T4?

A

conjugated into a huge inactive complex , lysosomal endocytosis transports back into follicular cell, proteolysis of complex releases thyroxine (t4) and triiodothyronine (T3)
excess iodide receyles into lumen to produce more hormone
T3 and T4 ready for secretion into blood

20
Q

why is T4 used as a medicine rather than t3

A

longer half life

easily converted to t3

21
Q

what is reverse t3?

A

inactive hormone, less than 1% of thyroid hormone production
t4 is easily converted to rT3

22
Q

name the four groups of thyroid anti-thyroid drugs ?]what are theorems

A 
Thyronine hormones : 
levothyroxine sodium (T4) ( tablets and oral solution)

liothyronine sodium (t3) (tablets and sole iv selection)

antithyroid drugs:
carbimazole (tablets)
propylthiouricil

23
Q

How do we get thyronine hormones to target tissues?

A

thyroxine conjugates with binding proteins which are synthesised in the liver, albumin (5-10%
thyroxine binding globulin (binds 70-75%) and transthyretin (TTR) (binds 20% and takes to CNS)

24
Q

Why is the liver important in thyroid disease?

A

liver disease leads to loss of effective t4 transport

25
Q

Describe the importance of thyroxine binding globulin?

A

large circulating reservoir binds to any t4 to prevent loss in the urine

26
Q

Describe the function and half life of thyroid binding hormones

A

TBG bind T3 and T4, half life 5 days
transthyretin binds T4 only half life of 2-3 days
albumin binds T3 (30%) and t4 (10%)
protein bound T4 and T3 20:1

27
Q

how are T3 and t4 transported into cells?

A

free (non protein bound) T3 and T4 enter cells by specific transporters (e.g. MCT8, MCT10 and OATP1c1)
t3 is bio active, t4 inactive, converted toT3 by intracelluclar iodthyronine deiodinases

28
Q

what are the types iodiothyronine deiodinases ? what do they do

A

DIO1 and DIO2 converts t4 into t3
DiO1 and DIO3 converts T4 into rT3
they are selenocysteine- containing enzymes
selenium accepts iodides

29
Q

where is DIO1 found

what is its major product

A

liver, kidney,muscle,thyroid

circluating T3

30
Q

where is DIO2 found

what is its major product

A 
areas of the CNS pituitary thyrotropes
intracellular T3 (important for feedback regsulation
31
Q

what is the importance of DIO3?

what is its major product?

A

rT3

protective enzyme - decreases high concentrations of thyroid hormone

32
Q

describe the thyroid hormone receptor

A

produced by TR(alpha) and TR(beta)
found in nucleus
heterodynes with retinoid X receptor
functions as a transcription factor i.e. binding to response element to increase transcription
binds to TRE
inhibit gene transcription when thyroid hormone not bound to it or in some cells binding decreases

33
Q

compare t3 and t4 binding affinity to TR

A

15: 1
t3: t4

34
Q

what affect does binding of T3 to the TR have on growth hormone concentrations?

A

increases them

35
Q

what affect does binding of T3 to the TR have on prolactin concentrations?

A

decrease

36
Q

what affect does binding of T3 to the TR have on concentrations of alpha and beta subunits of TSH?

A

reduce alpha and beta sub units of TSH

37
Q

what are the 5 biological actions of thyroid hormones

A 
control of basal rate
control of growth
foetal development
Cardiovascular effects
Musculoskeletal effects
38
Q

what problems can arise from iodine deficiency in foetus?

A

foetus: miscarriage, stillbirth, congenital abnormalities

39
Q

what problems can arise from iodine deficiency in childhood and adolescent

A

goiter - can be subclinical
impaired mental function
impaired physical development

40
Q

what problems can arise from iodine deficiency in neonates

A

neonatal loiter
neonatal hypothyroidism
impaired mental function

41
Q

how does thyroid have cardiovascular effects?

A 
T3 increases 
cardiac contraction and output
heart rate
oxygen supply
CO2 removal from tissues
INCREASED OUTPUT

inc of myocardial ca 2+ uptake
inc expression of alpha myosin heavy chain and decrease in delta
inc expression of Ryanadone receptor in SR

inc metabolism
thermogenesis
vasodilation
sensitivity to catecholamines

42
Q

how does thyroid have musculoskeletal effects?

A

T3 has a potent stimulatory effect on bone turnover
inc both formation and resorption
t3 inc linear bone growth after birth
T3 inc rate of muscle relaxation
normal skeletal muscle function requires T3

Pharm Year 3 Sem1 patient (12 decks)

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