Lecture & Vodcast 2 -- Exam 5 Flashcards
What occurs in the follicle of the thyroid gland?
thyroid hormone (TH) production
What is so special about the way thyroid hormone is synthesized?
only hormone synthesized extracellularly
What is colloid in the thyroid gland?
thick liquid where thyroid hormone is made
What is the precursor molecule for thyroid hormone?
tyrosine
When synthesizing thyroid hormone, tyrosine is converted into ____ and _____
MIT
DIT
What is the difference between the intermediate of thyroid hormones MIT and DIT?
MIT: C3 iodide
DIT: C3 & C5 iodide
The combination of DIT + DIT results in the formation of ….
T4 (inactive)
- most common in blood
The combination of MIT + DIT results in the formation of ….
T3 (active form)
What enzyme converts T4 into the active T3?
5’ deiodinase (removes 5’ iodine)
What enzyme converts T4 into the reverse T3?
type III deiodinase
What are the 7 steps of thyroid hormone synthesis?
- iodide trapping
- thyroglobulin synthesis
- iodination
- coupling
- endocytosis
- proteolysis
- secretion/recycling
What occurs during step 1 of thyroid hormone synthesis, iodide trapping?
Na/I symporter brings Na and iodide into cell
What occurs during step 2 of thyroid hormone synthesis, thyroglobulin synthesis?
thyroglobulin is made which is the source of tyrosine for later steps
** inside cell
What occurs during step 3 of thyroid hormone synthesis, iodination?
iodide is converted into iodine which combines with tyrosine
** apical side of cell
What occurs during step 4 of thyroid hormone synthesis, coupling?
MIT + DIT = T3
DIT + DIT = T4
** apical side of cell
What occurs during step 5 of thyroid hormone synthesis, endocytosis?
T4 / T3 is brought back inside cell to be recycled or stored to be secreted
What is the hypothalamic pituitary thyroid axis?
hypothalamus: TRH
pituitary: thyrotrophs sense TRH and release TSH
thyroid: TSH induces production and release of T4 and T3
Does somatostatin and dopamine __increase/decrease___ the release of TSH?
decrease
If you have just eaten what is the affect on TSH secretion?
increase (wants to increase metabolism)
If you are stuck in the snow for 12 hours what is the affect on TSH secretion?
decrease (wants to slow metabolism and preserve energy)
___ can directly AND indirectly negatively feedback to prevent TRH and TSH secretion
T4
What is the thyroid hormones primary role?
increase metabolism (increases after eating)
In primary hyperthyroidism, what is the affect on levels of T4, T3, and TSH
T3 & T4: increase
TSH: decrease
What is Graves disease?
autoantibodies that activate TSH receptor on thyroid causing increased T4 and T3 secretion
** hyperthyroidism
Does hyperthyroidism cause increased or decreased weight?
decreased (increased metabolism)
Why does hyperthyroidism cause a goiter?
thyroid gland swells due to constant stimulation of TSH by auto-Ab causing increased thyroid follicles size
In primary hypothyroidism, what is the affect on levels of T4, T3, and TSH?
T3 & T4: decrease
TSH: increase
Why does TSH levels increase in hypothyroidism?
no negative feedback due to lack of T3 and T4 so pituitary keeps making TSH
What is Hashimoto’s disease?
autoantibodies destroy thyroid follicles
- hypothyroidism
Does hypothyroidism cause increased or decreased weight?
increase (decreased metabolism due to underactive thyroid)
Why does hypothyroidism cause decreased heart rate (bradycardia)?
decreased sympathetic activity
Why do babies with hypothyroidism have decreased growth and cognitive issues?
thyroid hormone is important in growth and brain development
Hypercalcemia causes _________ nerve excitability
decreased
Hypocalcemia causes _________ nerve excitability
increased
Does hypo or hyper-calcemia cause tetany (spasms)?
hypocalcemia (increased nerve excitability)
What 3 places regulate Ca2+ balance?
gut, bones, kidneys
Osteoblasts or osteoclasts contain receptors for PTH, Vitamin D3 and estrogen.
osteoblasts (build bone)
Osteoblasts or osteoclasts contain receptors for calcitonin.
osteoclasts (breaks down bone)
What cells break down bone?
osteoclasts
What cells build bone?
osteoblasts
What are the 2 sources of vitamin D?
milk and sun
What is the role of Vitamin D in regards to calcium?
- regulates Ca2+ levels
stimulates formation of calbindin to remove Ca2+ out of cell
Vitamin D3 is converted into ___________ in the liver which is a intermediate for active vitamin D
25-OH-vitaminD3
What are the 2 forms of vitamin D made from 25-OH-vitamin D3?
1,25-OH- vitamin D3
24,25-OH- vitamin D3
Is 1,25-OH- vitamin D3 or 24,25-OH- vitamin D3 the active form of vitamin D?
1,25-OH- vitamin D3
When 1-alpha-hydroxlase acts on 25-OH-vitaminD3, what form of vitamin D made?
1,25-OH- vitamin D3
** active form
When 24-alpha-hydroxlase acts on 25-OH-vitaminD3, what form of vitamin D made?
24,25-OH- vitamin D3
** inactive form
Where are 1,25-OH- vitamin D3 24,25-OH- vitamin D3 located?
kidney
Hypocalcemia causes 1,25-OH- vitamin D3 or 24,25-OH- vitamin D3 to be made.
1,25-OH- vitamin D3
Hypocalcemia ___________ secretion of PTH
increases
Increased PTH secretion causes 1,25-OH- vitamin D3 or 24,25-OH- vitamin D3 to be made.
1,25-OH- vitamin D3
Low phosphate causes 1,25-OH- vitamin D3 or 24,25-OH- vitamin D3 to be made.
1,25-OH- vitamin D3
High 1,25-OH- vitamin D3 causes 1,25-OH- vitamin D3 or 24,25-OH- vitamin D3 to be made.
24,25-OH- vitamin D3
** too much 1,25 causes negative feedback on itself
vitamin D bind to receptor in gut which causes the production of _________
calbindin
What is the role of calbindin in the small intestine?
carrier Ca2+ out of cell so it can be taken into blood stream
In the intestines do Ca2+ and phosphate follow the same direction or go in opposite directions?
same direction
What is the role of chief cells in the parathyroid gland?
secrete parathyroid hormone in response to Ca2+ levels
** Ca2+ sensors
What is the role of oxyphil cells in the parathyroid gland?
provides structural integrity
Does high or low Ca2+ levels inhibit PTH secretion?
high
What is the caveat involving chief cell’s Gq receptor?
the release of intracellular calcium actually inhibits release of PTH
What is the role of the parathyroid hormone?
raises Ca2+ levels in blood
In the kidneys do Ca2+ and phosphate follow the same direction or go in opposite directions and why?
opposite
there would be too much salt and would cause kidney stones
hypocalcemia causes __increased/decreased__ PTH secretion which causes increased ___1-alpha-hydoxylase / 24-alpha-hydroxylase___ activity which results in ___1,25-OH- vitamin D3 or 24,25-OH- vitamin D3___ to be made causing ___increased/decreased___ Ca2+ reabsorption from the GI
increased
1-alpha-hydoxylase
1,25-OH- vitamin D3
increased
Osteoclasts break down bone under the stimulation of _____ in order to release Ca2+ to increase its levels in the blood
PTH
- done indirectly
How does PTH indirectly stimulate osteoclasts to breakdown bone to release ca2+?
osteoBLASTS have PTH receptors; when PTH binds to osteoBLASTS it releases cytokines to stimulate osteoCLASTS
What is estrogen’s effect on osteoblasts?
limits its ability to produce cytokines to activate osteoclasts (why in menopause decreased estrogen causes bone damage)
PTH causes __________ plasma Ca2+ and ________ plasma phosphate
increase
decrease
What is the role of calcitonin?
decreases Ca2+ levels and increases phosphate levls
** opposes PTH
What cell produces calcitonin?
C-cells
How does calcitonin decrease Ca2+ levels?
binds to osteoclasts to prevent their function
Vitamin D deficiency results in _____calcemia
hypocalcemia (decreased GI reabsorption b/c no calbindin produces to move Ca2+ out of GI cells)
In hyperparathyroidism, what is the effect on PTH, Ca2+ and PO4- levels?
increased PTH
increased Ca2+
decreased PO4
(elevated Ca2+ is not feeding back to decrease PTH)
Increased calcium can lead to kidney _________
stones
increased PTH leads to what effect on bones?
increased degradation (due to trying to increase Ca2+ levels)
Elevated calcium not caused by hyperparathyroidism is a result of ______
PTHrP (tumor of the parthyroid gland)
PTHrP binds to osteo______ similar to PTH causing their activation
osteoBLASTS
(go on to activate osteoclasts via cytokines)
Why does PTHrP cause a vicious cycle?
it causes release of Ca2+ from bones but that Ca2+ can feed the cancer
PTHrP can also bind to PTH receptor in kidneys to stimulate Ca2+ _________ and phosphate _________
Ca2+ reabsorption = hypercalcemia
phosphate secretion