Thyroid Gland + Aldosterone+ Androgens

Question 1

Aldosterone is a mineralocorticoid
Receptors are present in organs of ___

1.Aldosterone acts on:

uThe ___ convoluted tubules of the ___

uThe __ ___

uThe __ ___

2. Inc Na+_ ___
3. Inc K+____
4. 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

Answer 1

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

2. é Na+ retention.
3. é K+ excretion.
4. 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

Question 2

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

Answer 2

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

Question 3

Aldosterone secretion is regulated by the renin-angiotensin system.

1. When the volume or pressure of blood perfusing the kidney___, the ____ cells secrete a proteolytic enzyme renin into the ___ ___
2. Renin cleaves angiotensinogen, a protein from the ___, to form angiotensin I, a __apeptide.
3. Angiotensin I is cleaved by angiotensin converting enzyme (ACE), a peptidase, to form angiotensin II, an __apeptide hormone.
4. Angiotensin II ___ the blood pressure, and stimulates secretion of ___e by the adrenal zona ___a cells.

Answer 3

1. When the volume or pressure of blood perfusing the kidney falls, the juxtaglomerular cells secrete a proteolytic enzyme renin into the blood stream.
2. Renin cleaves angiotensinogen, a protein from the liver, to form angiotensin I, a decapeptide.
3. Angiotensin I is cleaved by angiotensin converting enzyme (ACE), a peptidase, to form angiotensin II, an octapeptide hormone.
4. Angiotensin II raises the blood pressure, and stimulates secretion of aldosterone by the adrenal zona glomerulosa cells.

Question 4

___ in Plasma K levels can also stimulate aldosterone release

Answer 4

Increase in Plasma K levels can also stimulate aldosterone release

Question 5

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

Answer 5

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

Question 6

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

Answer 6

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

Question 7

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 __ __ __

Answer 7

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

Question 8

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

Answer 8

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

Question 9

The thyroid is a composite tissue with several endocrine functions.

Sits like a ___

___ the larynx

Answer 9

The thyroid is a composite tissue with several endocrine functions.

Sits like a bowtie

Below the larynx

Question 10

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

Answer 10

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

Question 11

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

Answer 11

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

Question 12

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

Answer 12

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

Question 13

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

Answer 13

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

Question 14

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

Answer 14

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

Question 15

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.

Answer 15

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.

Question 16

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

Answer 16

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

Question 17

Deficiency of iodineà ____

Answer 17

Deficiency of iodineà Goiter

Question 18

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____

Answer 18

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

Question 19

Regulation of thyroid hormone secretion

1. The hypothalamus secretes____ releasing hormone (TRH) in response to inputs from the __ __ ___
2. The anterior pituitary secretes ___ in response to ___
3. TSH stimulates ___ and ___ of thyroid follicle cells.
4. TSH stimulates each of the steps in the previous slide.
5. TSH acts via the ___ ___ – __ ___ –___ __ ___ cascade.
6. Thyroid hormones exert___ feedback on secretion of___. They diminish expression of genes that enable t____s to respond to ___

Answer 19

1. The hypothalamus secretes thyrotropin releasing hormone (TRH) in response to inputs from the central nervous system.
2. The anterior pituitary secretes TSH in response to TRH.
3. TSH stimulates growth and metabolism of thyroid follicle cells.
4. TSH stimulates each of the steps in the previous slide.
5. TSH acts via the adenyl cyclase – cyclic AMP –protein kinase A cascade.
6. Thyroid hormones exert negative feedback on secretion of TSH. They diminish expression of genes that enable thyrotrophs to respond to TRH.

Question 20

____ is like most of the time inhibitory

Answer 20

Somatostatin is like most of the time inhibitory

Question 21

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

Answer 21

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

Question 22

Thyroid hormones in blood

In healthy adults ~___% of the T4 is protein-bound.

1. The protein-bound T4 is 100 nM while the free T4 is 0.02 nM.
2. 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

Answer 22

Thyroid hormones in blood

In healthy adults ~99.98% of the T4 is protein-bound.

1. The protein-bound T4 is 100 nM while the free T4 is 0.02 nM.
2. 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

Question 23

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%)

Answer 23

T4

uTBG ( 70-75%)

uTTR (15-20%)

uAbumin (5-10%)

T3

uTBG (70-75%)

uAlbumin (25-30%)

Question 24

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%)

Answer 24

T4

uTBG ( 70-75%)

uTTR (15-20%)

uAbumin (5-10%)

T3

uTBG (70-75%)

uAlbumin (25-30%)

Question 25

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

Answer 25

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

Question 26

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

Answer 26

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

Question 27

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

Answer 27

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

Question 28

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___

Answer 28

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

Question 29

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

Answer 29

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

Question 30

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

Answer 30

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

Question 31

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

Answer 31

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

Question 32

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

Answer 32

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

Question 33

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.

Answer 33

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.

Question 34

Thyroid hormone is necessary for the regular progression of__ ___and ___

uThyroid hormone accelerates ___ of the ___ and ___

Answer 34

Thyroid hormone is necessary for the regular progression of tooth development and eruption.

uThyroid hormone accelerates shedding of the hair and skin

Question 35

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 ___ ___, ___ ___ ___, ____ ___, ___ ___, ___ ___ ___

Answer 35

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…

Question 36

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

Answer 36

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

Question 37

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”

Answer 37

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”

Question 38

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.

Answer 38

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.

Question 39

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

Answer 39

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

Question 40

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

Answer 40

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

Question 41

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

Answer 41

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

Question 42

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

Answer 42

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