Thyroid Gland + Aldosterone+ Androgens Flashcards
Aldosterone is a mineralocorticoid
Receptors are present in organs of ___
1.Aldosterone acts on:
uThe ___ convoluted tubules of the ___
uThe __ ___
uThe __ ___
- Inc Na+_ ___
- Inc K+____
- Regulated by ___, and ____ ___
Acts on kidneys, sweat glands and intestinal mucosa
K will stimulate Aldos secretion
That is bc heart is very sensitive to K. Can trigger ___ which can be deadly.
Angiotensin II also stimulates aldosterone
Aldosterone is a mineralocorticoid
Receptors are present in organs of excretion
1.Aldosterone acts on:
uThe distal convoluted tubules of the kidneys
uThe sweat glands
uThe intestinal mucosa
- é Na+ retention.
- é K+ excretion.
- Regulated by K, and angiotensin II
Acts on kidneys, sweat glands and intestinal mucosa
K will stimulate Aldos secretion
That is bc heart is very sensitive to K. Can trigger arrhythmia which can be deadly.
Angiotensin II also stimulates aldosterone
Role of aldosterone in regulating blood pressure
Renin angiotensin aldosterone system is very important for regulating blood P and blood volume
If blood volume ___(ECF ____), Decrease BP, Nervous Stimuli, ___, or Urine Na [] , that will be sensed by the___ (JG apparatus)
The kidney will then secrete ____
That will convert ___ to ___
___ will converted I à II
Angiotensin II will stimulate the adrenal cortex to secrete ___
Leads to ____ of Na. Water follows
Will lead to ___ in blood volume
Increase in blood volume will then feed back and ___ this process
Compounds that inhibit converting enzyme will inhibit action of aldosterone (ACE inhibitiors) so important for patients wit ___ BP
nRole of aldosterone in regulating blood pressure
Renin angiotensin aldosterone system is very important for regulating blood P and blood volume
If blood volume falls (ECF depletion), Decrease BP, Nervous Stimuli, NE, or Urine Na [] , that will be sensed by the kidney (JG apparatus)
The kidney will then renin
That will convert angiotensinogenà angiotensin I
Angiotensin converting enzyme will converted I à II
Angiotensin II will stimulate the adrenal cortex to secrete aldosterone
Leads to reabsorption of Na. Water follows
Will lead to increase in blood volume
Increase in blood volume will then feed back and inhibit this process
Compounds that inhibit converting enzyme will inhibit action of aldosterone (ACE inhibitiors) so important for patients with high BP
Aldosterone secretion is regulated by the renin-angiotensin system.
- When the volume or pressure of blood perfusing the kidney___, the ____ cells secrete a proteolytic enzyme renin into the ___ ___
- Renin cleaves angiotensinogen, a protein from the ___, to form angiotensin I, a __apeptide.
- Angiotensin I is cleaved by angiotensin converting enzyme (ACE), a peptidase, to form angiotensin II, an __apeptide hormone.
- Angiotensin II ___ the blood pressure, and stimulates secretion of ___e by the adrenal zona ___a cells.
- When the volume or pressure of blood perfusing the kidney falls, the juxtaglomerular cells secrete a proteolytic enzyme renin into the blood stream.
- Renin cleaves angiotensinogen, a protein from the liver, to form angiotensin I, a decapeptide.
- Angiotensin I is cleaved by angiotensin converting enzyme (ACE), a peptidase, to form angiotensin II, an octapeptide hormone.
- Angiotensin II raises the blood pressure, and stimulates secretion of aldosterone by the adrenal zona glomerulosa cells.
___ in Plasma K levels can also stimulate aldosterone release
Increase in Plasma K levels can also stimulate aldosterone release
Adrenal Androgens
General info
They are ____: they ___ protein synthesis in peripheral tissues. This is the opposite of the action of ___
This anabolic action may assist th ___ __ ___ in females
Not very effective in males bc they are overpowered by testosterone
Adrenal Androgens
General info
uThey are anabolic: they increase protein synthesis in peripheral tissues. This is the opposite of the action of cortisol
uThis anabolic action may assist the pubertal growth spurt in females
Not very effective in males bc they are overpowered by testosterone
Adrenal Androgens
General info
uThe adrenal androgens can cause ______ if present in excessive amounts. This may occur as the result of an adrenal tumor
uThe adrenal androgens, especially ______, can serve as the substrate for __ ___ in___ tissue as well as in the ___ ____endocrine glands
u
Adrenal Androgens
General info
uThe adrenal androgens can cause masculinization if present in excessive amounts. This may occur as the result of an adrenal tumor
uThe adrenal androgens, especially androstenedione, can serve as the substrate for estrogen synthesis in adipose tissue as well as in the estrogen-secreting endocrine glands
u
Adrenal Androgens
Adrenal gland secretes both male and female sex hormones in ___ sexes
uDehydroepiandrosterone (DHEA)
FOnly adrenal sex hormone that has any ___ ____
FOverpowered by __ ___ in males
FPhysiologically significant in females where it governs
- Growth of ___ and ___ hair
- Enhancement of __ __ ___
- Development and maintenance of __ __ __
Adrenal gland secretes both male and female sex hormones in both sexes
uDehydroepiandrosterone (DHEA)
FOnly adrenal sex hormone that has any biological importance
FOverpowered by testicular testosterone in males
FPhysiologically significant in females where it governs
- Growth of pubic and axillary hair
- Enhancement of pubertal growth spurt
- Development and maintenance of female sex drive
Corticosteroids
uA. may cause severe inflammatory responses
uB. stimulate protein synthesis
uC. increase muscle mass
uD. may produce hypoglycemia
uE. Cause fluid retention and edema
u
Corticosteroids
uA. may cause severe inflammatory responses
uB. stimulate protein synthesis
uC. increase muscle mass
uD. may produce hypoglycemia
uE. Cause fluid retention and edema
u
The thyroid is a composite tissue with several endocrine functions.
Sits like a ___
___ the larynx
The thyroid is a composite tissue with several endocrine functions.
Sits like a bowtie
Below the larynx
Unique features of the Thyroid Gland
Only endocrine gland easily ___ and ___
Th are the only ones needing a trace element (___) for production of active hormone
Th is stored ___ in a proteinaceous material called thyroid ___
Th have no cell membrane receptor but act like steroids and bind to ___ receptors
Thyroid hormones require Iodine for their production
Th: Thyroid Hormone
Still protected but its extracellular
Unique features of the Thyroid Gland
Only endocrine gland easily seen and palpated
Th are the only ones needing a trace element (I) for production of active hormone
Th is stored extracellularly in a proteinaceous material called thyroid colloid
Th have no cell membrane receptor but act like steroids and bind to nuclear receptors
Thyroid hormones require Iodine for their production
Th: Thyroid Hormone
Still protected but its extracellular
Thyroid follicles: clumps of cells surrounding a lumen filled with colloid.
Follicular cells secrete ___
Parafollicular__ cells secrete ___
Parathyroids (not shown) secrete ___
Follicular cells secrete this colloidal material and it is in this colloidal material that Th are stored
In order for thyroid hormone to be released have to be reupatken by the follicular cells and passed to the blood stream
PTH regulates Ca
Thyroid follicles: clumps of cells surrounding a lumen filled with colloid.
Follicular cells secrete thyroid hormones
Parafollicular C-cells secrete calcitonin
Parathyroids (not shown) secrete parathyroid hormone (PTH).
Follicular cells secrete this colloidal material and it is in this colloidal material that Th are stored
In order for thyroid hormone to be released have to be reupatken by the follicular cells and passed to the blood stream
PTH regulates Ca
Thyroid hormones are iodinated amino acids
Made from ___
Tyrosine gets iodinated
Both of these hormones are active but __ is the most active form
In order for hormone to be active, inner ring needs to have 2 I
1 or 2 I on outer ring and you will be active
Inner ring needs 2 I for it to be active
If you have 2 on outer and 1 on inner ringà reverse T3à Inactive
The abundance of hormone in the body is ___
Thryoid Gland releases mainly T4
Within the peripheral tissues T4 gets converted to T3
T4 is a _____. Needs to be converted to T3 to have greater activity
Thyroid hormones are iodinated amino acids
Made from tyrosine
Tyrosine gets iodinated
Both of these hormones are active but T3 is the most active form
In order for hormone to be active, inner ring needs to have 2 I
1 or 2 I on outer ring and you will be active
Inner ring needs 2 I for it to be active
If you have 2 on outer and 1 on inner ringà reverse T3à Inactive
The abundance of hormone in the body is T4
Thryoid Gland releases mainly T4
Within the peripheral tissues T4 gets converted to T3
T4 is a prohormone. Needs to be converted to T3 to have greater activity
Hormones are stored and attached to protein called ___
T4 is attacheds to thyroglobulin
Stored in___ in this form
When its needed its taken up back into the cell, ___ and that releases the ___
T3, T4 and Reverse T3 are all stored and taken back up
Hormones are stored and attached to protein called thyroglobulin.
T4 is attacheds to thyroglobulin
Stored in colloid in this form
When its needed its taken up back into the cell, cleaved and that releases the T4
T3, T4 and Reverse T3 are all stored and taken back up
Thryoid gland is good at concentrating iodine
Iodine doesn’t’t have any other purpose in the body
___ moves into the cell along its gradient
E from this will help move Iodide against its gradient into the cell
Iodide gets into cell
Gets taken out of cell
As it passes thru the membrane, we have a ___ enzyme that will oxidize it from ___–> ___
Iodine then gets incorporated into molecules and these tyrosine molecules are attached to ___
You can have 1 or 2 iodine attached to benzene ring
Then these can ___ to form T3 and T4 or reverse T3
When body needs Th, e___ occurs. cell pinches off a piece of thyroglobulin molecule
Any piece that’s pinched off will have many of these attached.
Fuse with___ enzymes and then those will cleave it from ___ and T3/T4 gets released
Can then go to peripheral tissues
Thryoid gland is good at concentrating iodine
Iodine doesn’t’t have any other purpose in the body
Na moves into the cell along its gradient
E from this will help move Iodide against its gradient into the cell
Iodide gets into cell
Gets taken out of cell
As it passes thru the membrane, we have a peroxidase enzyme that will oxidize it from iodideàiodine
Iodine then gets incorporated into tyrosine molecules and these tyrosine molecules are attached to thryoglobulin
You can have 1 or 2 iodine attached to benzene ring
Then these can couple to form T3 and T4 or reverse T3
When body needs Th, endocytosis occurs. cell pinches off a piece of thyroglobulin molecule
Any piece that’s pinched off will have many of these attached.
Fuse with lysosomal enzymes and then those will cleave it from thryroglobulin and T3/T4 gets released
Can then go to peripheral tissues
Thyroid Hormones
General Information
uThe parathyroid glands, located ___ the thyroid, secrete parathyroid hormone (PTH).
uThe thyroid gland is made up of ___, clumps of cells that surround a lumen that is filled with colloid.
uThe follicular cells secrete the thyroid hormones, ___ and ____
uBetween the follicles are ___ and parafollicular or C-cells. The C-cells secrete calcitonin.
General Information
uThe parathyroid glands, located behind the thyroid, secrete parathyroid hormone (PTH).
uThe thyroid gland is made up of follicles, clumps of cells that surround a lumen that is filled with colloid.
uThe follicular cells secrete the thyroid hormones, thyroxin and triiodothyronine.
uBetween the follicles are capillaries and parafollicular or C-cells. The C-cells secrete calcitonin.
Thyroid hormone synthesis and secretion
Synthesis
uUptake of ___ from the bloodstream by ___ transport.
uOrganification: iodide is ___ and incorporated into t___ residues in the protein thyroglobulin producing ___ and ____
uSome MIT and DIT residues undergo ___ to form T3 and T4 residues, still in __ ___
uThyroglobulin containing T3 and T4 is ___ in the lumen of thyroid follicles as colloid.
uThyroglobulin is taken into the cells by ___
uHydrolysis of thyroglobulin to __ ___, including T3 and T4 in the phagolysosomes
uSecretion of __ and ___ into the extracellular fluid.
u
u
Synthesis
uUptake of iodide from the bloodstream by active transport.
uOrganification: iodide is oxidized and incorporated into tyrosine residues in the protein thyroglobulin producing monoiodotyrosine (MIT) and diiodotyrosine (DIT).
uSome MIT and DIT residues undergo coupling to form T3 and T4 residues, still in peptide linkage.
uThyroglobulin containing T3 and T4 is stored in the lumen of thyroid follicles as colloid.
uThyroglobulin is taken into the cells by endocytosis.
uHydrolysis of thyroglobulin to amino acids, including T3 and T4 in the phagolysosomes
uSecretion of T4 and T3 into the extracellular fluid.
u
u
Deficiency of iodineà ____
Deficiency of iodineà Goiter
Regulation of Thyroid Hormone
Hypothal: Secretes TRH
TRH gets placed into capillaries and taken to ant pit
TRH binds to thyrotropic cells and these cells secrete TSH
TSH goes to thyroid gland where it has a receptor on follicular cells
Then all of the processes just discussed except the peroxidase activity will occur.
The only process that is not dependent on TSH is____
Hypothal: Secretes TRH
TRH gets placed into capillaries and taken to ant pit
TRH binds to thyrotropic cells and these cells secrete TSH
TSH goes to thyroid gland where it has a receptor on follicular cells
Then all of the processes just discussed except the peroxidase activity will occur.
The only process that is not dependent on TSH is iodideàiodine
Regulation of thyroid hormone secretion
- The hypothalamus secretes____ releasing hormone (TRH) in response to inputs from the __ __ ___
- The anterior pituitary secretes ___ in response to ___
- TSH stimulates ___ and ___ of thyroid follicle cells.
- TSH stimulates each of the steps in the previous slide.
- TSH acts via the ___ ___ – __ ___ –___ __ ___ cascade.
- Thyroid hormones exert___ feedback on secretion of___. They diminish expression of genes that enable t____s to respond to ___
- The hypothalamus secretes thyrotropin releasing hormone (TRH) in response to inputs from the central nervous system.
- The anterior pituitary secretes TSH in response to TRH.
- TSH stimulates growth and metabolism of thyroid follicle cells.
- TSH stimulates each of the steps in the previous slide.
- TSH acts via the adenyl cyclase – cyclic AMP –protein kinase A cascade.
- Thyroid hormones exert negative feedback on secretion of TSH. They diminish expression of genes that enable thyrotrophs to respond to TRH.
____ is like most of the time inhibitory
Somatostatin is like most of the time inhibitory
Thyroid hormones in blood
Thyroid hormones travel in the blood bound to ___
___ __ ___ carries 70-75% of T4.
______ also called______) carries 15-20% of T4.
uSerum ___ carries 5-10% of T4.
uT3 is bound to ___(70-75%) and ___ (25-30%)
u
Thyroid hormones in blood
Thyroid hormones travel in the blood bound to proteins
uThyroid‑binding globulin (TBG) carries 70-75% of T4.
uTransthyretin (TTR, also called thyroid‑binding pre‑albumin, TBPA) carries 15-20% of T4.
uSerum albumin carries 5-10% of T4.
uT3 is bound to TBG (70-75%) and albumin (25-30%)
u
Thyroid hormones in blood
In healthy adults ~___% of the T4 is protein-bound.
- The protein-bound T4 is 100 nM while the free T4 is 0.02 nM.
- It is the free T4 concentration that correlates with the __ ___ to thyroid hormones.
Binding to transport proteins provides for__ ___ of the hormone to all of the cells along a ____
Only freee T3 and T4 are active
Ones that are bound to transport proteins are not active.
They just act as a storage so when more is needed it can be released.
Will take awhile, even if not producing any more Th for that to be used up
Same for T3. 0.05% is free
Thyroid hormones in blood
In healthy adults ~99.98% of the T4 is protein-bound.
- The protein-bound T4 is 100 nM while the free T4 is 0.02 nM.
- It is the free T4 concentration that correlates with the physiologic responses to thyroid hormones.
Binding to transport proteins provides for uniform delivery of the hormone to all of the cells along a capillary.
Only freee T3 and T4 are active
Ones that are bound to transport proteins are not active.
They just act as a storage so when more is needed it can be released.
Will take awhile, even if not producing any more Th for that to be used up
Same for T3. 0.05% is free
Thyroid hormones travel in the blood bound to proteins.
T4
uTBG ( 70-75%)
uTTR (15-20%)
uAbumin (5-10%)
T3
uTBG (70-75%)
uAlbumin (25-30%)
T4
uTBG ( 70-75%)
uTTR (15-20%)
uAbumin (5-10%)
T3
uTBG (70-75%)
uAlbumin (25-30%)
Thyroid hormones travel in the blood bound to proteins.
T4
uTBG ( 70-75%)
uTTR (15-20%)
uAbumin (5-10%)
T3
uTBG (70-75%)
uAlbumin (25-30%)
T4
uTBG ( 70-75%)
uTTR (15-20%)
uAbumin (5-10%)
T3
uTBG (70-75%)
uAlbumin (25-30%)
Thyroid hormones are activated or inactivated by ____, depending.
Deiodinase enzymes
These are the enzymes that can remove the iodine atom from thryoid hormones
5: Removes iodine from ___ ring
5’: removes from the ___ ring
Thyroid hormones are activated or inactivated by deiodination, depending.
Deiodinase enzymes
These are the enzymes that can remove the iodine atom from thryoid hormones
5: Removes iodine from inner ring
5’: removes from the outer ring
Thyroid hormones are activated or inactivated by deiodination, depending.
5’/3’- deiodinases convert thyroxin (T4) to ____, the active form of the hormone by removing I from the outer ring
Circulating T4 is a ___
The 5/3-deiodinase converts T4 to inactive ___ by removing I from inner ring.
Thyroid hormones and their metabolites may be converted to __ ___ products by coupling them to ___ ___, and then cleared into the ___
Persons with their thyroid removed have normal ___ levels if given oral ___ supplements,
Thryroid hromone are coupled with glucuronic acid and then cleared in the urine
Thyroid hormones are activated or inactivated by deiodination, depending.
5’/3’- deiodinases convert thyroxin (T4) to triiodothyronine (T3), the active form of the hormone by removing I from the outer ring
Circulating T4 is a prohormone.
The 5/3-deiodinase converts T4 to inactive reverse T3 by removing I from inner ring.
Thyroid hormones and their metabolites may be converted to water-soluble products by coupling them to glucuronic acid, and then cleared into the urine.
Persons with their thyroid removed have normal T3 levels if given oral T4 supplements,
Thryroid hromone are coupled with glucuronic acid and then cleared in the urine
Deiodinase enzymes
5’/3’-deiodinase acts on the outer ring
uTwo forms, type 1 present in high conc. In___ ___ ____ and generates ___ of the T3 that reaches the circulation
FType 1 ____by caloric restriction or __ ___and T3 levels ___ and so does ___ __
During times of hunger or crisis then a lot of T3 is not produced
High levels of T3 or T4 will ___e the BMR
If you don’t have access to food, why would you want to increase your metabolic rate. You aren’t supplying E to maintain that metabolic rate
Deiodinase enzymes
5’/3’-deiodinase acts on the outer ring
uTwo forms, type 1 present in high conc. In liver, kidney, thyroid and generates most of the T3 that reaches the circulation
FType 1 inhibited by caloric restriction or severe stress and T3 levels decrease and so does metabolic rate
During times of hunger or crisis then a lot of T3 is not produced
High levels of T3 or T4 will increase the BMR
If you don’t have access to food, why would you want to increase your metabolic rate. You aren’t supplying E to maintain that metabolic rate
Deiodinase enzymes’
uType __ found in___ ___ ___ and supply these tissues with T3 from plasma derived T4
uLocal generation of T3 in pituitary causes __ ___ of ___ or thyrotropin
FType 2 is __ ___by caloric restrictions so under low caloric conditions local T3 levels in the pituitary are ___ and no compensatoy___ in TSH levels occurs.
That enzyme is not affected by calorie intake
This enzyme is the one that generates T3 within the pit
Even in times of shortage of food, still make adequate T3 in the pituitary so pit doesn’t sense any change in levels of T3/T4
If pit sensed fall in T3 or T4 it will ___ TSH and that will further produce T3 and T4 ___ is ___ __ ___
By having local generation of T3 in pit, you have maintain adequate levels of TSH even in times of hunger and its not___
Deiodinase enzymes’
uType 2 found in pituitary, CNS, placenta and supply these tissues with T3 from plasma derived T4
uLocal generation of T3 in pituitary causes feedback inhibition of TSH or thyrotropin
FType 2 is not affected by caloric restrictions so under low caloric conditions local T3 levels in the pituitary are normal and no compensatoy rise in TSH levels occurs.
That enzyme is not affected by calorie intake
This enzyme is the one that generates T3 within the pit
Even in times of shortage of food, still make adequate T3 in the pituitary so pit doesn’t sense any change in levels of T3/T4
If pit sensed fall in T3 or T4 it will secrete TSH and that will further produce T3 and T4 which are not really needed
By having local generation of T3 in pit, you have maintain adequate levels of TSH even in times of hunger and its not increased
Thyroid Hormone Actions
____
uThyroid hormones ____ tissue respiration: O2___ and heat___
___ and ___ ___
uThyroid hormones stimulate body growth and central nervous system development in well‑nourished children.
u
Hyper: BMR is high…___ a lot of weight, release a lot o___t and they __ a lot
If Th is deficient at birth not supplied quickly then __ can occur and you will have __ ___
That’s why they look for this when babies are born
If given Th after brith can have catch up growth
However, if its given too late, CNS underdevelopment wont be reversed
Thyroid Hormone Actions
Respiration
uThyroid hormones increase tissue respiration: O2 consumption and heat production
Growth and CNS Development
uThyroid hormones stimulate body growth and central nervous system development in well‑nourished children.
u
Hyper: BMR is high…lose a lot of weight, release a lot of heat and they sweat a lot
If Th is deficient at birth not supplied quickly then MR can occur and you will have stunted growth
That’s why they look for this when babies are born
If given Th after brith can have catch up growth
However, if its given too late, CNS underdevelopment wont be reversed
Thyroid Hormone Actions
Deficiency
uIodine deficiency in children leads to ____
__ ___, ___ stature, ___ in motor development, ___ hair, ___ abdomen.
FLow levels of thyroid hormone if discovered shortly after birth may reverse the ___ effects but the ___ effects are i____e if not detected within a __ __ after birth
___ metabolism cause __ ___e, ___ sweating, ___ skin, weigh___ ___ cardiac output
u
u
Thyroid Hormone Actions
Deficiency
uIodine deficiency in children leads to cretinism
mental retardation, short stature, delay in motor
development, coarse hair, protuberant abdomen.
FLow levels of thyroid hormone if discovered shortly after birth may reverse the growth effects but the CNS effects are irreversible if not detected within a few days after birth
uDecreased metabolism cause cold intolerance, decreased sweating, dry skin, weight gain, low cardiac output
u
u
Thyroid Hormone Actions
Actions continued,Thyroid hormones
____ nervous system activity
___ carbohydrate___ from the intestine
___ rate of ___ and ___ ___
u ___r blood cholesterol levels
u
u
u
u
Actions continued,Thyroid hormones
ustimulate nervous system activity
u↑ carbohydrate absorption from the intestine
u↑ rate of carbohydrate and lipid metabolism
u lower blood cholesterol levels
u
u
u
u
Thyroid Hormone Actions
Actions continued, Thyroid hormones
___ the number of b-adrenergic receptors thus ____ ____ to epinephrine and noradrenaline
Fyou may not be able to administer __ __ containing ___e, as this can cause cardiac problems during hyperthyroid episodes
u Avoid ___ in these patients
uDo not treat patients with active thyroid disease
uMonitor b__ __e, minimize___
F
Th Increase number of B adrenergic Receptors
Heart has B1 receptors These are Responsible for heart rate and force of contraction
Excess hormone–> very sensitive even to normal levels of catecholamines (epi, NE)
If you give them a shot of epi, heart will be SOOO fast. Get palpitations. Very dangerous. These people should not be treated with epi in any form.
Excess thyroid levels have fast powerful contractions
Bc of this affect, much of the symptoms of excess Th is due to effect of catecholamines due to increases sensitivity to them
Stress causes release of Epi/NE and that further aggravates the situation
Thyroid Hormone Actions
Actions continued, Thyroid hormones
uIncrease the number of b-adrenergic receptors thus increasing sensitivity to epinephrine and noradrenaline
Fyou may not be able to administer local anesthetics containing epinephrine, as this can cause cardiac problems during hyperthyroid episodes
u Avoid Aspirin in these patients
uDo not treat patients with active thyroid disease
uMonitor blood pressure, minimize stress
F
Th Increase number of B adrenergic Receptors
Heart has B1 receptors These are Responsible for heart rate and force of contraction
Excess hormone–> very sensitive even to normal levels of catecholamines (epi, NE)
If you give them a shot of epi, heart will be SOOO fast. Get palpitations. Very dangerous. These people should not be treated with epi in any form.
Excess thyroid levels have fast powerful contractions
Bc of this affect, much of the symptoms of excess Th is due to effect of catecholamines due to increases sensitivity to them
Stress causes release of Epi/NE and that further aggravates the situation
Thyroid Hormone Actions
uT3 stimulate ____ of mineralized mature bone. Th stimulate bone turnover.
uTh is required for___ bone growth after birth but matures __ ___ in fetal bones
FTh stimulate bone resorption by increasing local release of resorptive____ such as ___
FIncreased levels of ____ signals bone resorption.
uT3 receptors on osteoblasts stimulate bone formation as evidence by an increase in ___ and__ ___ levels.
Thyroid Hormone Actions
uT3 stimulate remodeling of mineralized mature bone. Th stimulate bone turnover.
uTh is required for linear bone growth after birth but matures growth centers in fetal bones
FTh stimulate bone resorption by increasing local release of resorptive cytokines such as interleukins.
FIncreased levels of hydroxyproline signals bone resorption.
uT3 receptors on osteoblasts stimulate bone formation as evidence by an increase in osteocalcin and alkaline phosphatase levels.
Thyroid hormone is necessary for the regular progression of__ ___and ___
uThyroid hormone accelerates ___ of the ___ and ___
Thyroid hormone is necessary for the regular progression of tooth development and eruption.
uThyroid hormone accelerates shedding of the hair and skin
Mechanism of Action of Thyroid Hormone
T4 gets converted T3
T3 crosses membrane
Bind to thyroid receptor which is usually bound to another receptor called Retnoid X receptor
This complex binds to TRE (thyroid response element) part of DNA
That increases tx of ___ ___, ___ ___ ___, ____ ___, ___ ___, ___ ___ ___
T4 gets converted T3
T3 crosses membrane
Bind to thyroid receptor which is usually bound to another receptor called Retnoid X receptor
This complex binds to TRE (thyroid response element) part of DNA
That increases tx of B receptors, Na/K pump, gluconeogenic enzymes, resp enzymes, myosin heavy chain…
Thyroid hormone (T3) acts through a genomic mechanism.
The T3 receptor (TR) is located in the nucleus, bound to a__ __ ___(TRE) in the DNA as a heterodimer with a ___ __ ___r (RXR).
uWhen T3 binds to the TR, the activity of RNA polymerase ___ is altered leading to a change in the pattern of gene expression
u
Thyroid hormone (T3) acts through a genomic mechanism.
The T3 receptor (TR) is located in the nucleus, bound to a thyroid response element (TRE) in the DNA as a heterodimer with a retinoid X receptor (RXR).
uWhen T3 binds to the TR, the activity of RNA polymerase II (pol II) is altered leading to a change in the pattern of gene expression
u
Graves Disease
B lymphocytes synthesize immune globulins that bind to and activate ___ receptors
u___ ___ ↑, T3 and T4 synthesis ___
uThyroid ___ to produce a ___
uUntreated person becomes ___
___ metabolic rate with weight loss, sweating ___ interolerance,___ and more ___heart beat, muscle ___ and wasting, tremulousness, difficulty ___ and changes in ___ ___and skin __
___ enlargement of the thyroid
This is a hyperthyroid state.
Can occur thru different methods.
One important way is shown on next slide.
As T3 and T4 increase, what will decrease? TSH and TRH
As TSH decreases, thyroid gland will atrophy
Thyroid enlarges to produce a goiter
“Hold that thought…Im not sure we can have a goiter”
Graves Disease
B lymphocytes synthesize immune globulins that bind to and activate TSH receptors
uIodide trapping ↑, T3 and T4 synthesis ↑
uThyroid enlarges to produce a goiter
uUntreated person becomes hyperthyroid
F↑metabolic rate with weight loss, sweating heat intolerance, rapid and more forceful heart beat, muscle weakness and wasting, tremulousness, difficulty concentrating and changes in hair growth and skin texture.
FSymmetrical enlargement of the thyroid
This is a hyperthyroid state.
Can occur thru different methods.
One important way is shown on next slide.
As T3 and T4 increase, what will decrease? TSH and TRH
As TSH decreases, thyroid gland will atrophy
Thyroid enlarges to produce a goiter
“Hold that thought…Im not sure we can have a goiter”
Graves Disease
Abnormal immunoglobulin is called __ __ ___
uTSI also stimulate connective tissue in the ____ muscles leading to___ and forward ___ of the eyes (___).
uAlso seen is a ____of the skin over the lower legs.
TSI binds TSH receptor on follicular cells and act like TSH.
Once it binds, thyroid will release T3 and T4
TSI also stimulates conn tissue.
Forces the eye out the socket
Diplopia: Double vision
You will get a goiter bc TSI acts like TSH
You have goiter in presence of Low TSH
TSH is low because we feedback and inhibit it
Normally when we get a goiter its because of ___ TSH
In this case you still get a goiter even with low TSH because TSI is acting like TSH.
Graves Disease
Abnormal immunoglobulin is called thyroid-stimulating immunoglobulin (TSI)
uTSI also stimulate connective tissue in the extraocular muscles leading to diplopia and forward protrusion of the eyes (exophthalmos).
uAlso seen is a thickening of the skin over the lower legs.
TSI binds TSH receptor on follicular cells and act like TSH.
Once it binds, thyroid will release T3 and T4
TSI also stimulates conn tissue.
Forces the eye out the socket
Diplopia: Double vision
You will get a goiter bc TSI acts like TSH
You have goiter in presence of Low TSH
TSH is low because we feedback and inhibit it
Normally when we get a goiter its because of Excess TSH
In this case you still get a goiter even with low TSH because TSI is acting like TSH.
Hypothyroidism
Women ___ affected than men
uMost common cause worldwide is __ ___
uMost common cause in the US is an __ ___: ___ ____
FCaused by ___ antibodies vs thyroid ___cells, microsomes and___ receptors
FAb blocks and destroy ___ function
F___ TSH but ___ T3 and T4 levels
Low Th
Inhibition on ant pit removed
Release TSH
That stimulates Thyroid gland
Goiter is easy to see
Hypothyroidism
Women more affected than men
uMost common cause worldwide is iodine deficiency
uMost common cause in the US is an autoimmune disorder Hashimoto thyroiditis
FCaused by antithyroid antibodies vs thyroid follicular cells, microsomes and TSH receptors
FAb blocks and destroy thyroid function
FElevated TSH but normal T3 and T4 levels
Low Th
Inhibition on ant pit removed
Release TSH
That stimulates Thyroid gland
Goiter is easy to see
Hypothyroidism
Symptoms of hypothyroidism
uPainless ___, ___ changes, peripheral___, constipation, headache, joint aches, fatigue and in women ___
uCheck TSH levels in women with ___. Sometimes these patients develop other ____ disorders
___ coma can be life-threatening. Hypothermia and coma evolve slowly
Females who have amenorrhea (abnormal absence of menstruation) that could be due to low thyroid hormones
Low BMR
Everything is slowed down in the body
These Th stimulate degredation of ___ (glycoproteins that have ability to absorb a lot of water)
Without Th, GAGs accumulate and absorb a lot of H20. That gives you the edema
Hypothyroidism
Symptoms of hypothyroidism
uPainless goiter, skin changes, peripheral edema, constipation, headache, joint aches, fatigue and in women anovulation
uCheck TSH levels in women with amenorrhea. Sometimes these patients develop other autoimmune disorders
uMyxedema coma can be life-threatening. Hypothermia and coma evolve slowly
Females who have amenorrhea (abnormal absence of menstruation) that could be due to low thyroid hormones
Low BMR
Everything is slowed down in the body
These Th stimulate degredation of GAG (glycoproteins that have ability to absorb a lot of water)
Without Th, GAGs accumulate and absorb a lot of H20. That gives you the edema
Hyper
Primary: defect at thyroid gland. TSH is ___
Secondary hyper: At level of pit. Can have ___ in TSH or __ __ in TSH
Hypo:
Primary Low T4, ___ TSH (bc no inhibition by T4)
Secondary: Low T4, ___ TSH or __ change
Hyper
Primary: defect at thyroid gland. TSH is low
Secondary hyper: At level of pit. Can have increase in TSH or no change in TSH
Hypo:
Primary Low T4, High TSH (bc no inhibition by T4)
Secondary: Low T4, LowTSH or no change
In your exam of your patient, look for this
Large tongue bc things haven’t been broken down (macroglossia)
Enlarge salivary glands
Enamel hypoplasia
Thick lips bc things not broken down
Hyper:
Osteoporosis: Bone resorption is outpacing bone formation
In your exam of your patient, look for this
Large tongue bc things haven’t been broken down (macroglossia)
Enlarge salivary glands
Enamel hypoplasia
Thick lips bc things not broken down
Hyper:
Osteoporosis: Bone resorption is outpacing bone formation
