Mstn Ii - Lecture 33

Front 1

thyrotropin releasing hormone (TRH)

where it's made and released:
structure:

Back 1

hypothalamus synthesize and release TRH

- 3 AA neuropeptide produced in the parvoventricular nucleus

Front 2

once at the anterior pituitary, the TRH:

Back 2

bind to the TRH receptors located on the thyrotroph cells -> these cells produce TSH

Front 3

after TSH is made, it:

structure:

Back 3

- travels to the thyroid -> thryoid produces thyroid hormones

- structure: glycoprotein made up of an alpha and beta subunit
- all glycoproteins share the same alpha unit, but different beta subunits.

Front 4

TSh binds to the TSH receptors on the thyroid gland:

Back 4

- thyroid -> triiodothyronine (T3) and thyroxine (T4)
- T4 is the predominant hormone that circulates

Front 5

5'thyroxine deiodinase

Back 5

converts T4 when it enters the cell, removes one iodide molecule -> T3 is made locally inside the target tissue.

Front 6

T3, T4 regulate:

Back 6

- negatively exerts negative feedback on the hypothalamus and pituitary gland.

Front 7

low levels of 5'-thyroxine deiodinase:

Back 7

then T4 will bind and exert its effect, but it won't be as avid as T3's effect

Front 8

thyroid gland histology:

- where thyroid hormones are store:
- cells activated and activated:

Back 8

- follical surround a colloid matrix that stores thyroid hormone
- when not activated, the thyroid cells = cuboidal appearance
- binding of TSH on the basolateral side stimulate thyroid cells -> causes the cells, increase in size and produce invaginations into the colloid
- allows an increase in the apical surface area to capture more of the colloid matrix to break out the thyroglobulin -> release of T3 and T4

Front 9

thyroid hormones are:

Back 9

created by tyrosine and iodide via the iodinase enzyme.
- monoiodotyrosine
- diiodotyrosine
- combine these 2 to give T3 and T4

Front 10

once TSH binds to the TSH receptor, what happens inside the thyroid cells:

Back 10

- binding causes an increase in cAMP
- cAMP stimulates the active transport of iodide against its concentration gradient -> bringing iodide into the cell via the Na/K ATPase

Front 11

once inside the thyroid cell, the iodide:

Back 11

- organification process where it is attached to a thyroglobulin molecule.
- via a hydrogen peroxidase driven coupling, it is sent into the colloid and stored as thyroglobulin

Front 12

cAMP:

Back 12

- drives all steps in the thyroid hormone production
- stimulate active transport of iodide
- increases the endocytosis of the thyroglobulin

Front 13

lysosome in the thyroid hormone production pathway:

Back 13

- after thyroglobulin is endocytosed, lysosome is stimulated for proteolysis of the thyroglobulin -> T3 and T4 diffuse out of the thyroid cell through the basolateral plasma membrane and into circulation

Front 14

TSH's effects on the thyroid cell:

Back 14

- increase cAMP -> increase iodination, coupling, proteolysis, diffusion of thyroid hormones
- increases the number of thyroid cells and the size of the cells

TSH stimulates hormone production but also for the size and structure of the thyroid cells

Front 15

T3 and T4's effects:

Back 15

- stimulate transcription (mRNA)
- increase Na/K ATPase
- increase Mito, respiratory enzymes
- increase other enzymes/proteins/hormones

Front 16

low physiological levels of thyroid hormone:

high levels of TH for long periods:

Back 16

low: anabolic effect on other cells

high: catabolic and cause the breakdown of stored substances such as muscle mass

Front 17

increase TH:

Back 17

- body requires more energy
- stimulate food intake by stimulating appetite centers to bring in the necessary substrates for the oxidative processes that produce cellular energy.
- stimulate mobilization of carbs, proteins and fats
- direct effect on cardiovascular tissues by increasing the appearance of beta-adrenergic receptors -> increase uptake of oxygen -> usfeul in the increased oxidative processes.
- increase in ventilation to allow better oxygen delivery to the tissues
- production of heat: TH uncouples proteins -> interfere with the normal electron flow, producing heat: TH involved in thermogenesis

Front 18

when TH hormones are elevated for a good length of time:

Back 18

reduction in muscle mass and fat tissue to the catabolic effect

Front 19

when a person is placed in cold:

Back 19

- increase in TSH level in the blood

dramatic in children

Front 20

when a person is placed in warm environment:

Back 20

decreases TRH release thereby decrease T3 and T4 release

dramatic in children

Front 21

primary hypothyroidism

Back 21

defect in thyroid gland so cannot produce adequate T3/T4

lack the ability to have long loop negative feedback -> high levels of TSH in the plasma

Front 22

primary hypopituitarism

Back 22

defect in pituitary so cannot produce adequate TSH -> no T3/T4

Front 23

primary hyperthyroidism

Back 23

too much T3/T4 -> excessive negative feedback -> low levels of TSH in the blood

Front 24

inject TRH

normal person:
primary hypothyroidism:
primary hyperthyroidism:

Back 24

normal: stimulate production and release of TSH into the bloodstream -> levels decline according to normal half-life

hypothyroidism: enormous rise in TSH -> due to the lack of TH -> loss of negative feedback -> dramatic increase in the # of TRH receptors on the thyrotophs to compensate.

hyperthyroidism: excessive negative feedback -> reduces # of TRH receptors -> no rise in TSH after TRH injection because TRH is downregulated and desensitized

Front 25

Graves Disease

Back 25

- hyperthyroidism
- autoimmune condition where the body produces thyroid stimulation immunoglobulin -> bind to TSH receptors -> activates the production and release of TSH -> increase TH
- bulging eyes: TH stimulate production of proteoglycans -> accumulate in the interstitial spaces such as the eyes -> draw in water -> swelling
- increase in hormones increases fibroblast growth around the eyes

Front 26

Goiters

Back 26

- not enough iodine
- body cannot produce enough thyroid hormones
- deficiency in T3/T4 decreases the negative feedback -> see an increase in TRH/TSH.
- increase in TSH -> hypertrophy and hyperplasia of thyroid cells - guioter

goiters are not absolute sign of iodine deficiency... could be graves

Front 27

distinguish between hyper or hypothyroidism:

Back 27

- take blood sample and measure TSH level

if high: patient = hypothyroidism
low: hyperthyroidism

Front 28

Cretinism

Back 28

- prenatal or neonatal deficiency in thyroid hormone levels
- decrease stimulation of brain matter growth by decresing myelination and branching
- mental retardation

Front 29

Myxedema

Back 29

- adult form of cretinism
- hypothyroidism
- added fat deposition in the periphery and midsection
- deposition of mucopolysaccarides in the interstitial spaces of the periphery causing water build up and edema.
- poor wound healing so they may have a lot of bruises on their body.
- thinning of the skin, constipation, cold intolerance, and reduced appetite yet increased fat and water accumulation

Front 30

adult hyperthyroidism

Back 30

- accelerated heart rate -> due to increased beta-adrenergic receptors on the heart
- increased rate of respiration
- increased appetite with little weight gain/weight loss
- diarrhea due to increase GI motility
- heat intolerance
- jittery state of nature

Front 31

thyroid storm

Back 31

when hyperthyroidism: lots of beta-adrenergic receptors: if operate, likely to aggravate the area and release catecholamine into circulation -> acceleration in cardiac activity -> high heart rate -> ventricular fibrillation (Thyroid storm)

to avoid this: give patients beta-blockers to block the beta adrenergic effect

Front 32

excess iodide:

Back 32

decreases thyroid hormone and thyroid gland.

short term: inhibit the production of thyroid hormone and decreases the thyroid gland tissue size