Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
108 Cards in this Set
- Front
- Back
|
what are some of the most common endocrine disorders
|
thyroid problems
|
|
|
what are the 2 active forms of thyroid hormone, which is MORE active? which is more abundant
|
T3
T4 **T3, is MORE active **T4 is more abundant |
|
|
so if T3 is more active than T4 but more T4 is secreted how to the tissues ensure they get enough thyroid hormone
|
they convert T4 to T3 at the tissue
|
|
|
colloid is found where, what does it contain
|
in the lumen of follilcles
**thyroglobulin, like pre thyroid hormone. is endocytosed into the surronding follicular cells(needs to be iodinated?!) |
|
|
what are 3 uniquie features of TH synthese
|
1. needs LOTS of I2 from diet
2. done intra/extracellulary 3. T4 is major secretory product but its not the most active (T3 is active) |
|
|
what is colloid in the strictest sence of the word
|
TG with T4 T3 DIT and MIT bound
**colloid is stored in this form until TSH is released to stim release |
|
|
how do we see TH in circulation
|
BOUND!
1. TBG 2. Prealbumin 3. Albumin 4. Free **only hte FREE is active to TGB serves to make a resevoir of TH in circulatio that can be activated very wuickly |
|
|
why do we have TH circulating bound to TBG
|
so that we have some TH in the blood ready to act fast when it gets the signal
**only free TH is active |
|
|
what happens to TH levels in liver failure
|
1. no liver no TBG
2. No TGB, free TH 3. transient increase in TH will inhibit the production of TH (-) feedback |
|
|
what happens to TH with pregnancy
|
lots of estrogen keeps TBG around, this decreases the amt of free TH.
**the transient decrease in TH will cause the TH to increase syntheiss **recall in liver failure there was a transtien increase which caused production of TH to decrease |
|
|
what is the way to measure TBG in circulation
|
T3 resin uptake test
|
|
|
what is the T3 resin uptake test
|
way to measure TBG in circulation
|
|
|
wht turns T4 into T3 at the target tissue
|
5'iodinase
**does so by removing 1 I2 |
|
|
what happens to 5'iodinase in starvation?
|
this converts T4 to T3
**inactive in starvation in most tissues except brain **inhibiting 5"iodinase in sk mm will decrease O2 consumption and decrease BMR **BUT the brain remains active |
|
|
the main regulation of TH secretion is what? how does it wotk
|
Hypothalamic-Pituitary Axis
1. Hypothalamis releases TRH 2. TRH acts on pituitary to release TSH (thyrotrophs of the ant pit) 3. TSH acts on thyroid to release T4/T3 |
|
|
what was the first gland to be recognized as an endocrine gland? is this also the largest endocrine gland?
|
thyroid
also the largest, has a high blood flow rate! |
|
|
what sorts of thing are associated with TH
|
growth
maturation metabolic rate heat production energy metabolizm |
|
|
does the thyroid fx in utero?
|
yep?
At 12 weeks its secreted TH |
|
|
is the fetal hypothalamus pituitary axis fx?
|
sure it
**it plays a critical role in development of CNS and fetal growth |
|
|
what happens to a fetus who doest get TH for some reason, perhaps the fetal hypothalmaus/pititary/thyrpid axis is off
|
mental retaradion: poor CNS development
wont grow |
|
|
what is the fx unit of the thyrpid
|
follicular cell:
lume is full of colloid, storage site for horomoens, has |
|
|
where is colloid? what does it contain
|
its the extracellular part of follicular cells role in TH synthesis. its int he lumen
**it have thyroglobulin (TG) **storage site for hormoens, recall the weird stroage site for TH (peptise is in vesicle) |
|
|
other than follicular cells what cell is in the thyroid
|
clear cells.
aka P cells **secrete calcitonin to reduce PTH, acts in opposition of the parathyroid |
|
|
what does calcitoni do? what secretes it?
|
decreases blood calcium levels. secreted by C cells (parafollicular) cells in the THYROID
*OPPOSES PTH From parathyrid |
|
|
how can we look at the colloid to determine the activity of the thyroid
|
Hyperthyroid: not lots of colloid in lumen, it is being reabs
Hypothyroid: excess of colloid, non is being reabs Normal Thyroid: prbly some chunks taken out |
|
|
what are the 4 major steps of TH synthesis
|
1. take up I
2. Organification: incorproate I into tyrosine on TG 3. Coupling of iodinated Tryosines to form TH 4. Diffusion of thyroid hormone into the blood |
|
|
how is I taken from the blood into the follicular cell
|
Na/I pump, symport
**Iodide trap: I moves against gradient, Na moves with electrochemical gradient |
|
|
what is the first thing that happens in the colloid when we are making TH
|
Organifiction
I is added to tyrosine |
|
|
what are 3 key things to remember about TH synthesis
|
1. I must come from diet
2. TH synthese is intra and extracellular 3. T4 is major product but T3 os more active |
|
|
what is the prohormone T3 ot T4
|
T4, it is peripherally modified
|
|
|
WHEN WE refer to the intra and extracelluar areas of TH synthesis what do we mean
|
Intracellular: what happen in the follicular cell (iodine enters, T3.T4.MIT.DIT are cleaved from TG)
Extracellular: the parts that happen int he colloid: oxidation, organification , coupling |
|
|
what are the stores of I that we have in the body
|
1. Thyroid: HUGE store
2. Plasma: smaller recerve |
|
|
after you ingest I what 2 things can happen
|
1. pee it out
2. keep it in plasma: the stuff in plasma can then either be excreted, remain in plasma or go to thyroid |
|
|
the first step of TH synthesis includes getting the start materials ready what are the atart materials adn how are they made
|
1. Tyrosine: comes from the body
2. Iodide: taken up from the diet. Enters the follicular cells via iodine trap: basolateral surface (near the BV) take 2 Na and 1 I in. synport |
|
|
what does the Na/I trap do
|
its on the basolateral surface of follicular cells
*brings in 2 Na with its conc/eletrical gradient, and 1 I is coupled to it AGAINST its gradient. |
|
|
how is the Na/I trap regulated
|
with decreased I in the blood this transporter is stimulated
**cant keep up in severe deficiency |
|
|
can the expression if the Na/I transporter maintain I levels in the thyroid in severe depletion?
|
nope, it will only upregulat a bit but cant sustain prolonged deficiency
|
|
|
what drugs inhibit the Na/I trap
|
perchlorate
thiocyanate **block I uptake to decrease TH synthesis |
|
|
so we know that low I in the diet increases the activity of the Na/I trap, what else helps us conserve I when its low?
|
Kidney: reduce excretion, conserve reabs
Use T3 instead of T4 (T3 has one less iodide) **if these mechs fail (the trap esp) there is a decrease in TH, hypothyroidism |
|
|
does hypothyroidism due to I defeicieny develop quickly?
|
nope, we have like 100 times more I in the thyroid than the plasma so we have reserves for like 2 months
**recall we also have conservation mechs. Kideny, increase trap, use more T3 |
|
|
what hormone stim the iodine trap
|
TSH from the ant pit in response to THR
|
|
|
so once we have used the I trap to get the I from the blood into the follicular cell it then passes through the apical membrane (via pendrin) into the colloid, what happens next
|
1. OXIDATION: iodide is oxidized to iodine (I- --> I2)
thyroid peroxidase 2. ORGANIFICATION: I2 attaches to tryosine on TG *when 1 I attaches, MIT. when 2 I attact DIT 3. Coupling: DIT + DIT = T4 DIT + MIT = T3 |
|
|
what is pendrin, megalin
|
carries I from the follicular cell across the apical membrane into the colloid where it is oxidixed nad organified
Megalin: carries the TG that has T3/T4/DIT/MIT across the basolateral membrane from the colloid into the follicilar cell |
|
|
what inhibitsthyroid peroxidase? what does this affect
|
PTU, inhibits several steps in TH synthesis
Osidation Organification |
|
|
what is TG where is it made?
|
thyroglobiliun, a large protein made in ER/Golgi
**sent to colloid, it has Tryosine that combines with iodine |
|
|
what is the result of organification
|
well inthe colloid, thyrpid peroxidase has already oxidized iodine and now the I2 is added to Try on TG
**when 2 I attach we get DIT **when 1 I attach we get MIT **organification is also done by thrypoiid peroxidase, |
|
|
what is wolff chiakoff effect
|
when there is lots of I in the diet organification (incorporation of I with Try on TG) is inhibited
**block TH synthesis with increased I in diet **temporary *due to decreased activity of Na/I trap |
|
|
what is it called when we cant orgaify I into Try on TG bc the Na/I trap has been inhibited by increased i in diet
|
wolffe CHaikoff
|
|
|
what enzyme catalyzes coupling, what happens
|
Thyroid peroxidase
the DIT and MIT fromend from organification (also thyroid peroxidase) are coupled to for T3 and T4 T4= DIT+DIT (FAST) T3= DIT+MIT (SLOW) **not all DIT and MIT are coupled, some stay on TG **at this pt the TH is made and ready but requires TSH for secretion **keep in mind thyroid peroxidase is inhibited by PTU |
|
|
what does T3/T4 look like (what stage in synthesis) when it needs TSH for secretion
|
its T3 and T4 bound to TG
**its just waiting for TSH to stimulate it so can be endocytoses by follicular cells |
|
|
secretion of TH is stim by what? how does it happen
|
TSH from Ant Pit
**we left the T3/T4 attached to TG in the colloid. now when it gets TSH the TG:T3:T4:DIT:MIT is endocytosed by megalin **the colloid fuses with lysosomes where proteases free the T3.T4 from the TG and they enter the blood **MIT and DIT are deiodinated and the liberated I is recycled |
|
|
in the follicular cell what happens to the the DIT and MIT that were liberated from TG
|
they are deiodinated by thyroid deiodinase
**the I is receycled adn the try is reused |
|
|
what brings I across the apical membrane?
what brines TG across the apical membrane |
pendrin: I from cell to colloid
megalin: TG from colloid to cell |
|
|
what are teh 7 steps of TH synthesis
|
1. Uptake: Na/I trap, increased with low dietary I. pendrin to cross apical surface
2. Oxidation: thyroid peroxidase 3. Organification: add I to try to make DIT/MIT, thyroid peroxidase 4. Coupling: DIT+DIT to make T4 FAST, DIT+MIT to make T3 slow. Thyroid peroxidase. TG with the T3/T4 sits here until TSH stim for release 5. Secretion: TSH stimulated, colloid engulfed via megalin 6. Hydrolysis:: the T3 T4 DIT and MIT are liberated from TG by proteases in lysosomes 7. DIT MIT are diiodinated. T3 T4 diffuse into the blood |
|
|
ok so what can inhibit the I trap? what is PTU
|
Inhibit trap: percholoate, thiocyanate, increased I in diet
PTU: propylthiouracil, inhibits peroxidase (used in oxidation, organification, and coupling) to decrease TH synthesis |
|
|
what are teh 3 things the thyroid makes
|
1. T4, LOTS prohormone is peripherally converted into T3 via deiodinase
2. T3, ACTIVE!!! 3. rT3 NOT ACTIVE |
|
|
what are 2 places we have deiodinases? what are type 1 2 3 deiodinases?
|
peripherally to convert T4 to T3
**in the follicular cells to free the I that is on the DIT and MIT that was on the TG (when the colloid is endocytosed and the products are cleaved from TG) 1. Liver, kidney, thyroid sk mm. activating. high blood flow, low affinity 2. Glial cells, pituitary, thyroid. activating. HIGH AFFINITY, super sensitive to regulation 3. bran, placenta, skin. inactivating |
|
|
what is the inactivating deiodinase? where is it
|
type 3. brain, placenta, skin
**the type 1 is in liver kidney thyroid sk mm ( high BF, low affinity) **the type 2 is in glial cells, pituitary, thyroid (HIGH affinity, tight regulation) |
|
|
how is TH found in plasma
|
little is free, most bound to protein
1. Thyroxine Binding Globulin TBG, super abundant 2. albumin 3. prealbumin binding pritein, **keep in mind, only the studd that is free can bind its receptor |
|
|
what 2 hormones inhibit TH secretion? how?what else?
|
dopamine
somatostatin **thses 2 are released from the hypothalmus to inhibit TSH **of course the end product. T3/T4 will inhibit. feedback to inhibit the hypothalamus AND ant pit |
|
|
what does dopamine and somatostatin do to TH
|
decrease release. from hypothalmus to decrease TSH
**of course the end product T3/4 will inhibit release as well. feedback on both the hypothalamus and ant pit |
|
|
how is TH secretion regulated
|
hypothalamic (TRH)
Pituitary (TSH, stim all steps of synthesis, required for endocytosis of colloid) |
|
|
what does TRH act on
|
thyroprophs in the ant pit, this causes them to release TSH
TSH then causes the thyroid to secrete T3.T4 and also makes the thyroid grow (trophic effect) |
|
|
waht does TSH do? when is it increased?
|
1. make thyroid secrete hormones
2. make thyroud gorw. trophic effects **recall TSH is stimulated to be made by thyrotrophs in the ant pit by TRH from the hypothalamus |
|
|
ok so TSH from ant pit binds to receptor on thyroid. we know the the thyroid will increase syntheiss if T3/4 and grow, what are the specifics? what mech is used
|
cAMP
1. TH secretion: increased I trap, increase iodination, coupling, endocytoses, proteolysis. Glucose oxidation, NADPH generation 2 Growth of Thyroid: increaed DNA, RNA, Protein, Phispholipid, cell size/number, increased follicle formation |
|
|
doe T3 feedback to the hypothalamus or ant pit to decrease synthesis
|
both
somatostatin and dopamine (from hypothalamus) also inhibit TH by inhibiting TSH |
|
|
how do T3/T4 work to feedbak
|
1. Inhibit Hypothalamus: inhibit release of TRH
2. Inhibit Ant Pit: inhibit TSH by down regulating TRH receptor on the thyrotrophs **T3 is te KEY regulator: supress TSH release and transcription of TSH gene |
|
|
in the pituitary how does T3 regulate? how does it get there
|
T3 made from T4 deiodination, Type 2 deiodinase
*KEY peripheral reguator to decrease TSH |
|
|
what does TH do at a traget cell
|
diffuses past PM, in the cytosol T4 is deiodinated to T3. (recall, must be free, no TBG)
T3 then binds to a nuclear receptor and the complex acts a a TF Controls: Growth, CNS, ANS, BMR, heart/lungs, Metabolism |
|
|
TSH uses what 2 path?
what about TH (T3.T4) |
TSH: cAMP
TH: SRE (diffuse through PM and bind receptor to alter gene expression) |
|
|
T3 downregulates what receptor where? this inhibits secretion of what
|
downregulated TRH receptor in the ant pit. this means that less TSH is secreted
|
|
|
what is the effect of graves disease
|
**AB that bind to and stimulateTSH receptors (its like exogenous TSH that is NOT controlled with feedback)
This causes increased T3.T4 but LOW TSH **the high T3 is cuusing a decrease in expression of TRH receptors, so TSH secretion is decreased. feedbact to ant pit |
|
|
TH works synergistically with what to promote bone growth
|
GH
Somatomedians |
|
|
how does TH promote bone maturation
|
ossification and fision of growth plates
**recall TH, GH, and somatomedians work synergistically to promote bone growth |
|
|
why do we screen for neonetal hypothyroidism
|
TH is good for CNS maturation,
decreased TH leads to retardation |
|
|
we know that in babies TH is good for CNS developemnt and a lack of TH can lead to retardation. wht is the effect of TH in the adult CNS (increase, decrease)
|
Hyperthyroidism: hyperexcitable, irritable
ypothyroidism: listless, slow speech, decreased mental capacity, decreased memory |
|
|
what does TH do to the ANS
**we know it affectes the CNS in both babies and adults |
ANS
**TH stim the SNS. TH upregulates B1 receptors in the heart |
|
|
why does treatment of hyperthyroidism with a b blocker help?
|
TH upregulates B1 in the heart
**if we can block this receptor we bring activity of b receptors to a normal level |
|
|
wht does TH do to BMR? does it do this in ALL tissues
|
increase O2 consumption and BMR via increased Na/K ATPase
*increased heat **EXCEPT in teh brain, gonads, spleen |
|
|
how does TH ater the Na/K ATPase? what effect does this have
|
increase the na/K pump
*this increases o2 consumption, increase BMR, increase temperature **This is NOT seen in the brain, balls or spleen |
|
|
what does TH do to the heart
|
well we know it will increase b1 receptors
**increased HR and CO, this ensures lots of O2 is being delivered bc there is an increase in O2 consumption with TH |
|
|
how does TH affect the lungs
|
increase RR
**increased O2 consumption so we want to keep O2 moving, increased RR is one way to ensure O2 delivery to tissies |
|
|
so what does Th do to metabolism
|
increased! we have increased Na/K so increased o2 consumption. we need to meet these needs.
get more glucose!!!!! 1. increase glucose abs from GI 2. glycogenolysis increased 3. gluconeogenesis increased 4. glucose oxidation increased 5. lipolysis increased 6. protein syntheiss/degradation. overall degradation, (-) N balance |
|
|
with a secretion of TH what do we want glucose to do
|
increase glucose available
**we have increased metabolism Gluconeogeneiss, glycogenolysis, lipolysis, glucose oxidation, |
|
|
the increase in O2 consumption with increased TH is the result of what? what are the results of this
|
increased O2 consumption caused by: increased Na/K ATPase
Causes: increase BMR, body temo NOT SEEN IN BRAIN, GONADS, SPLEEN |
|
|
as a result of increases RMR by TH metabolism wants to...
|
liberate glucose!
increase abs from GI, gluconeogenseis, glycogenolysis, lipolysis |
|
|
what happens to protein metabolism with TH secretion
|
synthesis and degradation. FUTILE
net effect is degradation, can lead to negatine protein balance **recall GH will cause a + Nitrogen balance |
|
|
what hormone leads to - N balance, +?
|
(-) TH
(+) GH |
|
|
what is the first sign of hyperthyrpoidism
|
increase HR and RR
|
|
|
what does T3 do to vascular resistance
|
decreases it
*may see a decrease in diastole |
|
|
B1 are increased by TH in what tissue
|
heart
sk mm adipocytes |
|
|
so in adults Th is catabolic (degradation exceeds synthesis) is this the case fetally
|
nope, anabolic fetally
**also works with GH to increase bone formation |
|
|
so if a kiddo has decreased TH can the effects be reversed?
|
well first need to know the effects are bone growth and retardation
**when caught at birth NORMAL DEVELOPMENT **if caught later growth can susally catch up but mental fx can still be low |
|
|
what is cretinism
|
defect in TH
deficit in growth and mental capacity |
|
|
TH has these effects:L
Growth CNS BMR METABOLISM CARDIO |
Growth: growth formatin, bone matruation
CNS: maturation BMR: Na/K, O2, Heat, BMR (all increase) METABOLISM: glucose abs, glycogenolysis, gluconeogenesis, lipolysis, protein catabolism (all icnrease) CARDIO: increase CO |
|
|
what are some of the specifics about hoe TH increases CO and HR
|
increase myosin
increase contractility decrease peripheral vascular Resistance (increased CO2 as a vasodilator) |
|
|
so what happens to TSH if we cant make T3/T4 due to I deficiency
|
increases
**T3/4 arent available to turn off the mechanism so more TSH is released, this makes the thyroid grow --> goiter |
|
|
the goiter seen as what kind of effect of what hormone
|
trophic effect of TSH
**with I deficieny we cant make T.3/4 but our body knows we need it and there is no T3/4 to inhibit TSH secretion. so TSH is just made and made and causes the thyroid to grow and gorw **goiter is a result of HYPOthyroidism |
|
|
Low levels of thyroid hormones
result in continuous release of TSH which grows the thyroid gland. why does this happen |
no TH to feedback adn inhibit the ant pit from releasing TSH
|
|
|
what is another name for adult onset hypothyroidism
|
hashimotos disease
|
|
|
so in hypothyroidism like hashimotos disease what happens to:
metabolic rate weight N balance heat production CO RR goiter? energy? mental capacity |
decreased metabolic rate
weight gain + N balance (normal TH is -) decreased heat production decreased CO decreased RR lethargic goiter yes growth/mental retardation |
|
|
if you have hypothyroidism what can caise it? what do TSH levels look like
|
hashitomotos thyroditis
removal of thyroid I defeicency Cretinism (congenital) decreased TRH or TSH **TSH is increased usually bc we dont have T3/4 inhibiting the mech **can be a decrease in TSH if primary defect is in hypothalmus or ant pit |
|
|
what does TSH look like with hypothryoidism due to I deficiency or hoshomotimo
|
increased
**no T3.4 to turn the mech off |
|
|
how is hypothyroidism tx
|
thyrpoid hormone replavement
**levothyroxine sodium (levothyroid, synthyroid, levoxine) *the drugs have longer 1.2 lives than T3 |
|
|
what is the disease where we make AB that mimic TSH?
|
graves disease, hyperthyroidism
**AB mimic TSH and bind to their receptors to increase T3/T4 we get LOTS of T3/4 bc its being made w/o regulation **TSH is low in this case |
|
|
expothalamus is seen in what thyroid condistion
|
graves
Hyperthyroidism |
|
|
how can hyperthryoidism be treated?
|
remove thyroid
radioactive I to kill the gland drugs to inhibit synthesis of TH (PTU, block peroxidase) B blockers |
|
|
what dose PTU, do?
What dose Methylthiouracil do// |
inhibit thyroid peroxidase: oxidation, organificaiton, coupling, converstionof T4 to T3
Methykthiouracil: blocks Na/I pump, oxidation and coupling **both are used to treat HYPERthyroidism |
