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Endocrine > Lecture 7 > Flashcards

Lecture 7 Flashcards

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1
Q

What is the blood supply to the thyroid gland?

A

Superior and Inferior thyroid arteries

Superior, middle, and inferior thyroid veins–>drain into internal jugular vein

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2
Q

What is the innervation of the thyroid gland?

A

Middle and Inferior cervical ganglion (sympathetic nervous system)

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3
Q

What is the thyroid glast derived from?

A

the brachial pounch endoderm

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4
Q

The epithelium of the thyroid gland are arranged in follicles that contain large storage of what?

A

thyroglobulin

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5
Q

What do inactivated follicles look like?

A

have flattened squamous eptihelium

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6
Q

What do follicular cells transform to when active?

A

cuboidal epithelium

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7
Q

What is the follicle of the thyroid gland?

A

epithelial cells surrounding lumen

  • lumen filled with colloid-30% of thyroid mass, thyroglobulin is major component
  • microvilli extend into the colloid
  • basement membrane-delineates follicle
  • close to fenestrated capillaries
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8
Q

What do the parafollicular cells (C cells) do?

A
  • produce calcitonin
  • other proteins that maintain follicle
  • do not touch colloid
  • contain many small granules
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9
Q

What are iodothyronines?

A

Thyroid hormones

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10
Q

What two precursors do they require?

A

TG and iodine(excess dietary iodide secreted in the urine)

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11
Q

What is the wolf-chaikoff effect?

A

an intrathyroid response that assures constancy of iodide storage in the face of changes in dietary iodide

-increases in iodide intake decrease gland transport and hormone synthesis, and vice versa

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12
Q

What are very high iodine doses used for clinically?

A

rapid shutdown of thyroid hormone production in hyperthyroid patients

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13
Q

WHat is the most preventable cause of mental retardation?

A

thyroid hormone deficiency
(ex cretinism)
-WHO campaign for all countries to have access to iodized salt

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14
Q

T4
half life
travel in the blood
binds

A

Thyroxine=T4

  • long half life 7-8 days
  • tightly bound to transport proteins in blood
  • binds with low affinity
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15
Q

T3

A

Triiodothyronine=T3

  • primary active form
  • most is converted intracellularly from T4
  • very low circulating
  • bind with high affinity, low capacity to receptor (don’t need much to saturate receptor)
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16
Q

rT3

A

Reverse triiodothyronine=rT3

-biologically inactive

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17
Q

What are the parts of the HPT axis?

A

Hypothalamus-PVN-Thyrotropin-Releasing Hormone (TRH)
-Negative feedback by T4/T3 synthesis

Pituitary-Thyrotropes
Thyroid Stimulating Hormone (TSH)
-negative feedback by intracellular T3(release) “thyroid sensor)

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18
Q

What tonically inhibits the TSH release?

A

somatostatin and dopamine

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19
Q

THe thyroid follicle is functionally polarized what is the apical surface exposed to what does it do?

A
  • exposed to the lumen (colloid)
  • thyroid hormone synthesis
  • Iodination of TG
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20
Q

What is basolateral surface exposed to? What does it do?

A

blood
iodine uptake “trap”
-thyroid hormone release

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21
Q

What are the 7 steps in thyroid hormone synthesis?

A
  1. Iodide trapping: TSH stimulates iodide trapping by increasing the activity of the NIS co-transporter in the basal membrane of the follicular epithelial cell

-NIS-sodium iodide symporter
(lithium inhibits symporter)

  1. Transport: oxidized by thyroid peroxidase to form iodine
  2. Iodination: Iodination of tyrosyl residues on thyroglobulin (in lumen)
  3. Conjugation: Conjugation of iodinated tyrosines to form T4 and T3-linked thyroglobulin (in lumen)
  4. endocytosis: conjugated thyroglobulin with T4/T3 enters follicular epithelial cell. Packaged in endosomes
  5. Proteolysis: TG, MIT, DIT, T4, T3 released from vesicle
  6. Secretion: T4/T3 secreted into circulation at basal membrane
    * All stps are stimulated by TSH
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22
Q

What inhibits NIS

A

lithium

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23
Q

What inhibits TPO(thyroid peroxidase)?

24
Q

What is T4 made with?

25
WHat is T3 made with?
1 MIT(outter ring)+ 1 DIT
26
Reverse T3 what is the outer ring?
DIT
27
Why would you use a radioactive iodide uptake test? | How does the radioactive iodide test work?
to determine function of thyroid gland 1. iodide is uptaken into thyroid epithelial cell 2. iodide is transported by the sodium iodide symporter 3. radioactive iodide and anions like pertechnetate can be transported by NIS Hot nodule=black cold nodule=light-->thyroid cancer
28
What is an organification defect?
iodine cannot be incorporated into tyrosine. Test by blocking NIS with inhibitor (ie. perchlorate)-no more can come in-rest just diffuses out
29
WHat does the line for graves disease look like?
hyperthyroid but also taking it up fast and dumping it fast
30
More T4 is produced and stored in the thyroid, what happens to 80% of T4 in the periphery?
Deiodinated to T3
31
Does T4 have low receptor affinity? WHat about rT3?
yes t4 low receptor affinity | rT3 has no biological activity
32
What does Type 1 deiodinase do? | Where is it? What does it make?
outer and inner ring deiodinase - liver, kidney, thyroid, skeletal muscle - primary source of T3 in circulation - will make T3 and reverse T3
33
What does Type 2 deiodinase do? | Where is it? What does it make?
Outer ring deiodinase Brain, pituitary, placenta, cardiac muscle Will only make T3 -thyroid hormone "sensor" in the pituitary
34
What does Type 3 deiodinase do? | Where is it? What does it make?
Inner ring deiodinase brain, placenta, skin -only make rT3 -protective since it is inactive Inner==reverse
35
Is thyroid hormone bound during transport? By what 3 things?
yes 99% bound TBG(70%) Thyroxine-binding globulin -T4 has highest affinity for this but TBG is lowest in concentration TRR (10%) Transthyretin Albumin (15-25%)
36
Is T3 or T4 more tightly bound? How does this affect their half life?
T4=tightly bound=longer half-life approx. 7 day T3=approx. 1 day
37
Can TBG reversibly release T4 onto target tissues?
yes, unique
38
What do estrogen and hepatitis increase?
TBG
39
What do nephrotic syndrome and steroids decrease?
TBG
40
Thyroid hormone receptors are part of the nuclear receptor family, same as steroid hormones, what does the receptor form a heterodimer with?
Retinoic acid Receptor
41
Where are thyroid hormone receptors expressed?
on nearly every cell type
42
What is T3 T4 affinity to the THR?
T3=high affinity low capacity | T4=low affinity very little biological activity at physiological concentrations
43
What does thyroid hormone do to the metabolism?
Increases basal metabolic rate - stimulates hepatic gluconeogenesis - stimulates proteolysis - stimulates lipolysis - overall increased energy/oxygen consumption, increased thermogenesis
44
Does thyroid hormone promote Brain maturation?
yes
45
Does thyroid hormone stimulate b-adrenergic receptors?
yes in heart, skeletal muscle, adipose tissue
46
How does T3 increase cellular oxygen consumption and heat production?
by increasing mitochondrial activity
47
What is the BMR, carbohydrate, protein, lipid, thermogenesis change with hypo and hyperthyroid?
1. BMR Hypo=decrease Hyper=increase 2. Carb Met Hypo=decreased gluconeogenesis and glycogenolysis normal serum glucose Hyper=increased gluconeogenesis and increased glycogenolysis normal serum glucose 3. Protein Metabolism Hypo=decreased synthesis and decreased proteolysis Hyper=increased synthesis and increased proteolysis -muscle wasting 4. Lipid Metabolism Hypo=decreased lipogenesis, decreased lipolysis, and increased serum cholesterol Hyper=increased lipogenesis, increased lipolysis, decreased serum cholesterol 5. Thermogenesis Hypo=decreased (cold intolerance) Hyper=increased (heat intolerance
48
T3 is critical for normal brain development, what does it do?
- neuronal cell migration/differentiation - myelination - synaptic transmission
49
What is cretinism a deficiency in? What does it lead to?
- iodine deficiency during development - short stature/impaired bone formation - mental retardation - delayed motor development
50
T3 increases cardiac output, resting heart rate and stroke volume increase, how is this affected in hyperthyroidism?
-arrhythmias due to increased beta adrenergic receptors
51
Why do you get goiter in both hyperthyroidism and hypothyroidism?
hypo-no negative feedback, so you get excess production of TSH -->hyperactive follicular cells hyper-making lots of thyroid hormone
52
What are 3 causes for a goiter(enlarged thyroid)?
cancer-3:1 women: men Hyperthyroid-Grave's disease Hypothyroid-Hashimoto's thyroiditis, iodine deficiency
53
What is grave's disease?
Autoimmune-antibodies stimulate TSH receptor (long-acting thyroid stimulator-LATS) -elevated T4/T3 (TSH will be low) -diffuse symmetrical goiters with hyperthyroid Symptoms: tachycardia, ophthalmopathy, irritability, hyperactivity, heat intolerance, weight loss, nervousness, muscle wasting
54
What is hashimoto's thyroiditis?
Autoimmune destruction of thyroid follicles antibodies against TPO and TG Diffuse goiter with hypothyroid symptoms: lethargy, fatigue , hair loss, cold intolerance, brittle nails, decreased appetite, weight gain
55
What is thyroid storm?
``` Emergency life threatening situation hyperthyroid coupled with severe acute illness symptoms: high fever tach altered mental status severe nausea, vomiting, diarrhea severe circulatory collapse--resulting in death ``` Treatment propylthiouracil (PTU-only acute treatment)-->inhibits thyroid peroxidase (TPO) -carbimazole-->inhibits TPO -beta blockers to restore normal heart function

Endocrine (11 decks)

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