patient sem 1 : Thyroid Flashcards
where is the thyroid gland?
the thyroid gland is found infront of the trachea and Adams apple
how many lobes does the thyroid have ?
2: left and the right , some people (10-30%) have a 3rds lobe - the pyramidal lobe
Describe the microscopic structure of the thyroid gland
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
what is the function of a parofollicular c cell?
production and secretion of calcitonin ( responsible for calcium homeostasis)
How is the thyroid gland regulated?
hypothalamus releases TRH
ant. pituitary releases TSH
thyroid gland releases Thyroid hormones (T3 and T4)
describe the differences between t3 and t4 (thyronine hormones)
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
what happens when there is a low body temperature
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
describe the effects of low t3 on thyroid gland
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
describe the effects of high t3 on thyroid gland
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
describe how TSH has an effect on the thyroid
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
name 4 functions of the thyroid cells
thyroglobulin synthesis
iodide pumping into follicular cells and follicular men
iodination by thyroid peroxidase
endocytosis,proteolysis and hormone release
What is thyroglobulin? where is it found
(backbone of thyronine synthesis), found in centre of follicles
how does iodide enter the follicular cells?
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
how is thyroglobulin produced?
produced by the endoplasmic reticulum in the follicular cells nd exocytosed into thyroid lumen
how are iodotryrosines formed and coupled in the thyroglobulin molecules
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)
what does DIT and MIT mean?
di- iodotryosine
mono-iodotyrosine
ROLE OF TPO?
addition of iodide to thyorogobulin backbone
conjugation and DIT and MIT
How are T3 and t4 formed
DIT + DIT = T4
MIT + DIT = T3
describe the release of T3 and T4?
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
why is T4 used as a medicine rather than t3
longer half life
easily converted to t3
what is reverse t3?
inactive hormone, less than 1% of thyroid hormone production
t4 is easily converted to rT3
name the four groups of thyroid anti-thyroid drugs ?]what are theorems
Thyronine hormones : levothyroxine sodium (T4) ( tablets and oral solution)
liothyronine sodium (t3) (tablets and sole iv selection)
antithyroid drugs:
carbimazole (tablets)
propylthiouricil
How do we get thyronine hormones to target tissues?
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)
Why is the liver important in thyroid disease?
liver disease leads to loss of effective t4 transport
Describe the importance of thyroxine binding globulin?
large circulating reservoir binds to any t4 to prevent loss in the urine
Describe the function and half life of thyroid binding hormones
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
how are T3 and t4 transported into cells?
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
what are the types iodiothyronine deiodinases ? what do they do
DIO1 and DIO2 converts t4 into t3
DiO1 and DIO3 converts T4 into rT3
they are selenocysteine- containing enzymes
selenium accepts iodides
where is DIO1 found
what is its major product
liver, kidney,muscle,thyroid
circluating T3
where is DIO2 found
what is its major product
areas of the CNS pituitary thyrotropes intracellular T3 (important for feedback regsulation
what is the importance of DIO3?
what is its major product?
rT3
protective enzyme - decreases high concentrations of thyroid hormone
describe the thyroid hormone receptor
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
compare t3 and t4 binding affinity to TR
15: 1
t3: t4
what affect does binding of T3 to the TR have on growth hormone concentrations?
increases them
what affect does binding of T3 to the TR have on prolactin concentrations?
decrease
what affect does binding of T3 to the TR have on concentrations of alpha and beta subunits of TSH?
reduce alpha and beta sub units of TSH
what are the 5 biological actions of thyroid hormones
control of basal rate control of growth foetal development Cardiovascular effects Musculoskeletal effects
what problems can arise from iodine deficiency in foetus?
foetus: miscarriage, stillbirth, congenital abnormalities
what problems can arise from iodine deficiency in childhood and adolescent
goiter - can be subclinical
impaired mental function
impaired physical development
what problems can arise from iodine deficiency in neonates
neonatal loiter
neonatal hypothyroidism
impaired mental function
how does thyroid have cardiovascular effects?
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
how does thyroid have musculoskeletal effects?
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
