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Block 3; Week 6 Michelle > Thyroid O'Driscoll > Flashcards

Thyroid O'Driscoll Flashcards

1
Q

How much does the thyroid gland?

A

15-20 grams

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2
Q

Where is the thyroid gland located?

A

below the larynx

anterior to the trachea

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3
Q

Describe the cellular composition of the thyroid gland.

A 
follicular cells
endothelial cells
parafollicular (C) cells
fibroblasts
lymphocytes
adipocytes
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4
Q

What happens in the follicular cells?

A

thyroid hormone synthesis

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5
Q

What is the fcn of the endothelial cells of the thyroid gland?

A

they line the capillaries that provide blood to the follicles

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6
Q

What is the function of the parafollicular (C) cells?

A

production of calcitonin, important in calcium metabolism

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7
Q

Describe the morphology of the thyroid follicular cells.

A

they are closed off follicles
lined w/ cuboidal epithelial cells
filled w/ colloid: mainly composed of thyroglobulin

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8
Q

What does the apical surface of the follicular/epithelial cells face? The basolateral side?

A

Apical: faces the lumen
Basolateral: faces the interstitium, the capillaries

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9
Q

What are the 2 main thyroid metabolic hormones?

A

T4 (thyroxine) & T3

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10
Q

What percentage of thyroid secretions are T4? What % are T3?

A

T4: 93% of secretions
T3: 7% of secretions

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11
Q

Which has a greater plasma conc’n: T3 or T4?

A

T4!!!

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12
Q

Which is more potent: T4 or T3?

A

T3!!

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13
Q

What is a second source of T3, aside from the thyroid gland?

A

Much of the T4 is converted into T3 once it reaches the tissues. This happens thru peripheral monodeiodination

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14
Q

What are the 5 factors involved in thyroid hormone synthesis?

A 
TSH
Thyroglobulin
Iodine
Membrane Transporters
Enzymes
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15
Q

What is the structure of thyroglobulin?

A

large glycoprotein w/ multiple tyrosine residues

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16
Q

Where is the thyroglobulin synthesized, secreted, & stored?

A

Synthesized: thyroid follicular cells
Secreted: thru apical membrane into follicular lumen
Stored: in the colloid, in the follicular lumen

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17
Q

What is the function of thyroglobulin?

A

it is a scaffold in the follicular lumen for thyroid hormone synthesis

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18
Q

Why is iodine important in the diet? How much iodine do you need each week?

A

important for thyroid hormone synthesis
1mg required per week…we get enough in our table salt
**most preventable global cause of mental retardation
**in higher elevations, less iodine in the soil

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19
Q

What are the basic steps of thyroid hormone synthesis?

A
  1. Iodide Trapping
  2. Formation & Secretion of Thyroglobulin
  3. Iodide Oxidation & coupling of Iodide w/ thyroglobulin
  4. Endocytosis of Thryoglobulin & release of thyroid hormones
  5. Recycling Iodide
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20
Q

What is iodide trapping?

A

process of concentrating iodide in the cell

influenced by TSH

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21
Q

Describe in detail Stage 1 of thyroid hormone synthesis, the iodide trapping.

A

Iodide is in the capillaries by the follicles.
NIS: Sodium Iodide Symporters bring iodide into the follicle cell.
This movement is driven by the Na/K pump.
Iodide gets into the follicular lumen via pendrin (a chloride-iodide counter transporter)

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22
Q

T/F The concentration of iodide in the follicular cells is much lower than in the blood.

A

False. It is 30X higher. Thus, when transporting iodide into the follicular cell, it is up a conc’n gradient.

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23
Q

What physical characteristic is important for the follicular cells to transport iodide?

A

their morphological polarization. Wider near the capillaries, room for transporters.

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24
Q

What is the second stage of thyroid hormone synthesis? How does this work?

A

thyroglobulin is formed & secreted.
it is formed in the ER & Golgi & secreted into the follicular colloid
each molecule of it has a ton of tyrosine AA
the thyroid hormones are made within the thyroglobulin molecule

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25
Q

What is stage 3 of thyroid hormone synthesis? How does it work?

A

the iodide is oxidized & coupled w/ thyroglobulin
Details:
*iodide gets into the lumen of the follicle & is oxidized by thyroperoxidase (TPO)
*once the iodine is oxidized it can combine w/ tyrosine AA w/i the thyroglobulin molecule (called organification)

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26
Q

Tyrosine is first iodized to ____ & then to ____.

A

MIT & then to DIT

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27
Q

What is T4 composed of? What is T3 composed of?

A

T4: DIT + DIT
T3: MIT + DIT

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28
Q

What is reverse T3?

A

An inactive form of T3 that can be formed.

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29
Q

What all does TPO or thyroperoxidase catalyze?

A

oxidation of iodide
organification of iodine/iodination of tyrosines on the scaffold of thyroglobulin
Synthesis of T3 & T4

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30
Q

What happens if someone doesn’t have activity of TPO?

A

their thyroid hormone production rate falls to zero

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31
Q

Where is some thyroid hormone stored? How much is stored?

A

follicular colloid, a part of the thyroglobulin molecule
**enough is stored here to supply the body with thyroid hormone for 2-3 months–>thus when you experience iodine deficiency you won’t see the fall in levels for several months…

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32
Q

Where are the plasma proteins that bind thyroid hormones synthesized?

A

the liver

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33
Q

What percentage of T3 & T4 are bound to plasma proteins?

A

99%

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34
Q

What are the 3 types of binding proteins for T3 & T4? What % of T3/T4 bind to each?

A

TBG: Thyroxine-Binding Globulin (70%)
Prealbumin (15%)
Albumin (15%)

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35
Q

What is another name for pre albumin?

A

transthyretin

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36
Q

What percentage of T3 is found free? What % of T4?

A

Free T3: 0.3%

Free T4: 0.03%

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37
Q

What’s the deal with plasma proteins? Do they get overwhelmed easily?

A 
They don't get easily saturated. 
Implications: 
*they are unsaturated
*They can store 3X their amount
*sudden changes in hormone secretion don't effect free thyroid very much...
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38
Q

Describe how pregnancy can alter thyroid hormone levels.

A 
Pregnancy
High Estrogen Levels
Binding Protein Synthesis increases
New Equilibrium b/w free & bound hormone
Increase in total thyroid hormone levels
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39
Q

Why do thyroid hormones have a large reserve? Why do they have a delayed clearance?

A

b/c they are bound to binding proteins (longer half-life)…stored in the blood & peripheral tissues

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40
Q

What is the half life of T3? T4?

A

T3: 1 day
T4: 6 days

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41
Q

Why is the half life of T3 so much shorter than T4?

A

b/c the binding proteins have a higher affinity for T4.

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42
Q

How are thyroid hormones excreted?

A

conjugated to glucuronic acid & excreted in bile

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43
Q

Which has a greater biological activity? T3 or T4?

A

T3!!

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44
Q

What is the main source of T3 that is used by the body?

A

that that is converted from T4 in the peripheral tissues

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45
Q

What percentage of the thyroid hormone released from the gland is T3? T4?

A

93% T4

7% T3

46
Q

What % of the T4 is deiodinated to form T3?

A

40%

47
Q

Which deiodinases are responsible for turning T4 into rT3?

A

DI & DIII

48
Q

Which deiodinases are responsible for turning rT3 into T2?

A

DI & DII

49
Q

Which deiodinases are responsible for turning T4 into T3?

A

DI & DII

50
Q

Which deiodinases are responsible for turning T3 into T2?

A

DI & DIII

51
Q

Where is deiodinase type I most active?

A

liver
kidney
thyroid

52
Q

Where is deiodinase Type II most active?

A 
brain
pituitary
thyroid
skeletal muscle
cardiac muscle
53
Q

Where is deiodinase Type III most active?

A

Brain
Placenta
Fetal Tissues

54
Q

Does DI cut the outer or inner ring?

A

both!

55
Q

Does DII cut the outer or inner ring?

A

outer ring only

56
Q

Does DIII cut the outer or inner ring?

A

inner ring only

57
Q

DI is a major source of what kind of T3?

A

T3 that is circulating

58
Q

DII is a major source of what kind of T3?

A

T3 that is produced in tissues

59
Q

What is the vibe of DIII? What does it protect?

A

It decreases T3 levels & protects the fetus & adult brain.

60
Q

Which form of thyroid hormone has a shorter latent period: T3 or T4?

A

T3–>active faster, after only 6-12 hours

61
Q

What happens after TSH binds to the TSH receptor on the thyroid gland?

A

G protein coupled receptor, an increase in cAMP.

Genomic & Non-genomic effects

62
Q

What are the genomic effects of TSH on the thyroid gland?

A

Increased Gene Transcription

Increase in NIS, Thyroglobulin, TPO, NO synthase, Growth factors

63
Q

What are the non-genomic effects of TSH on the thyroid gland?

A

An increase in cAMP
increased proteolysis of thyroglobulin (means more T3 & T4 release)
NIS activity increases (increased iodide trapping)
Increase in tyrosine iodination (T3 & T4 synthesis)

64
Q

What is the effect of TH on TSH or TRH (from the hypothalamus)?

A

It decreases them both. Negative feedback inhibition.
It also decreases the TRH receptor on the anterior pituitary.
this allows for a constant conc’n of free T3 & T4.

65
Q

Thyroid Hormone Receptors (TRs) have higher affinity for T3 or T4? What types of receptors are these? What effect do they have?

A

Higher affinity for T3
This is found in peripheral tissues
nuclear receptors–>change transcription
Increase in growth, cardiac output & metabolism

66
Q

Which TH effect is faster: genomic or non-genomic?

A

Non-genomic is faster.

67
Q

Where are the main sites of the non-genomic response?

A

plasma membrane
cytoplasm
cell organelles–>mitochondria

68
Q

What is the basic response to thyroid hormone?

A

Enhanced mobilization of carbs, fats, & proteins
Increase in O2 consumption
Increase in basal metabolic rate & heat production

69
Q

What does thyroid hormone do to carbohydrate metabolism?

A

Increased uptake of glucose in the cells
Enhanced gluconeogenesis
Increased glucose absorption in the GI tract

70
Q

What does thyroid hormone do to lipid metabolism?

A

Mobilizes fat stores
Increases Plasma FFA conc’n
Accelerates FA oxidation
Increases LDL receptors on liver–>decreases plasma cholesterol

71
Q

In a case of hypothyroidism: what would happen to plasma cholesterol?

A

It would increase plasma cholesterol.

72
Q

What would thyroid hormone do to nitrogen metabolism?

A

Increased Protein Synthesis

An even greater increase of protein degradation

73
Q

Why is it that an increase in thyroid hormone can cause a relative vitamin deficiency?

A

b/c with the increase in production of many enzymes–>need more vitamins

74
Q

If a person had hyperthyroidism & weight gain–>why would that be?

A

b/c increased thyroid hormone causes increased metabolic rate & appetite. Sometimes the appetite predominates.

75
Q

What is the effect of thyroid hormone on the skeletal system?

A

important for growth & bone maturation

76
Q

What is the effect of thyroid hormone on the central nervous system?

A

essential for maturation of the CNS during the perinatal period
cerebral & cerebellar growth
myelination
vascularization
axonal & dendritic density
cell migration & differentiation affected

77
Q

What is the effect of thyroid hormone on the cardiovascular system?

A

Blood flow & cardiac output increases (vasodilation)
Increase in heart rate
Increase in heart strength b/c of increase in enzymatic activity
Increase in systolic pressure
Increase in pulse pressure

78
Q

What would an intense, crazy increase in thyroid hormone do to heart strength?

A

It would decrease it b/c of long-term protein catabolism

79
Q

What is the effect of T3 on cardiovascular hemodynamics?

A 
T3 causes tissue thermogenesis
Body needs to get rid of heat
Decrease in systemic vascular resistance via NO production
Diastolic BP lowers
Decrease in afterload
RAAS activated
Increase in Preload
Increase in Cardiac Output
80
Q

What is the effect of thyroid hormone on respiration?

A

It increases the rate of metabolism & therefore O2 utilization…
Activates mechanisms that increase resp rate & depth

81
Q

What is the effect of thyroid hormone on GI?

A

It increases appetite & food intake.
It increases secretions & motility
Too much thyroid hormone: increased frequency of bowel movements
Too little thyroid hormone: constipation

82
Q

What is the effect of thyroid hormone on sleep?

A

exhausts muscles & CNS
Too much thyroid hormone: always tired, but can’t sleep
Too little thyroid hormone: sleep 12-14 hrs/day

83
Q

What does thyroid hormone do to muscle vigor?

A

a little increase in thyroid hormone: muscles react w/ vigor
Too much thyroid hormone: weakness b/c of protein catabolism
Too little thyroid hormone: sluggish muscles
**fine muscle tremor: sign of hyperthyroidism

84
Q

What does thyroid hormone do to the CNS?

A

increases excitatory effects
Hyper: nervousness, psychoneurotic tendencies
Hypo: lack of energy, dulled mental capacity

85
Q

What does thyroid hormone do to the autonomic nervous system?

A

increases the effects of sympathetic stimulation

86
Q

What does thyroid hormone do to pancreatic secretions?

A

More thyroid hormone
more glucose metabolism
more insulin secretion

87
Q

What does thyroid hormone do to pituitary secretions?

A

More thyroid hormone
Less TSH
More GH

88
Q

What are the main categories of primary hyperthyroidism?

A

Graves’ Disease
Hyperfunctioning Thyroid Nodules
Therapy-Induced Hyperthyroidism (excess T3 & T4 substitution)
Thyroiditis

89
Q

What are the main categories of secondary hyperthyroidism?

A

TSH secreting pituitary adenomas

90
Q

What are the symptoms of hyperthyroidism?

A 
Highly Excitable
Heat Intolerance
Increased Sweating
Weight Loss
Increased frequency of bowel movements
Muscle Weakness
Nervousness
Fatigue w/o sleep
Hand tremor
91
Q

What are the main categories of primary hypothyroidism?

A 
Hashimoto's Disease
Endemic Colloid Goiter (dietary iodine deficiency)
Congenital Hypothyroidism (Cretenism)
Defects of Hormone Synthesis
Treatments for Hyperthyroidism
Thyroid Surgery & Radiation Therapy
92
Q

What are the main categories of secondary hypothyroidism?

A

Disorders of the anterior pituitary or hypothalamus

93
Q

What are the symptoms of hypothyroidism?

A 
Fatigue
Muscular Sluggishness
Low HR & CO
Weight Gain
Constipation
Mental Sluggishness
Myxedema
Cold Intolerance
Hoarseness
Goiter
Hypercholesterolemia
94
Q

What type of a disease is Graves’?

A

diffuse toxic goiter

an autoimmune disease

95
Q

What are some examples of hyper functioning thyroid nodules? What happens w/ these?

A

Examples: toxic adenoma, toxic multinodular goiter
Causes hyper secretion of thyroid hormone
Low TSH
other part of thyroid (not toxic nodule) inhibited from excreting thyroid hormone.

96
Q

What’s the deal w/ thyroiditis causing primary hyperthyroidism?

A

this is inflammation of the thyroid gland

can cause excess thyroid hormone stored in the gland to leak out into the bloodstream

97
Q

With TSH secreting pituitary adenomas…what disease do you have? What are the T4, T3 & TSH levels like?

A

This is secondary hyperthyroidism
TSH high
T4 & T3 high
**b/c of the adenoma, can’t stop producing TSH even tho there is negative feedback from thyroid hormones

98
Q

If you have goiter, do you have hyper or hypothyroidism?

A

Could have either. Goiter is present in either.

99
Q

In Grave’s Disease…do you have hypo or hyperthyroidism? What is the mechanism? What are the levels of T3, T4, & TSH?

A

High T3 & T4
Low TSH (b/c of negative feedback
Hyperthyroidism
**antibodies called TSI: thyroid-stimulating immunoglobulins form & activate the TSH receptors on the thyroid gland.

100
Q

What are 3 main symptoms of Grave’s Disease?

A

Goiter (hypertrophy & hyperplasia of the thyroid gland)
Pretibial Myxedema (deposition of CT–>cutaneous & dermal edema)
Graves’ opthalmopathy

101
Q

What are the 2 forms of Graves’ opthalmopathy?

A 
Exophthalmos (protusion of the eyeballs)
Thyroid Stare (eyes going in strange directions)
102
Q

What causes exophthalmos?

A

the autoimmune rxn causes edema of the retro-orbital tissues & degeneration of the extra-ocular muscles

103
Q

What is an example of something that causes secondary hypothyroidism? What does this do to TSH, T3, T4 levels?

A

Disorders of the anterior pituitary or hypothalamus–>this impairs TSH release
T3, T4 & TSH will all be low

104
Q

With Hashimoto’s Disease…what are the TSH, T3, & T4 levels? What are some of the things that can cause this?

A

High TSH
Low T3 & T4
**antibodies against thyroglobulin, thyroperoxidase, TSH receptor blockers
**sometimes thyroiditis can deteriorate the thyroid tissue & lead to fibrosis–stops secretion of thyroid hormones

105
Q

What can you see in a histo slide of thyroid gland that indicates Hashimoto’s disease?

A

lymphocyte infiltration of the thyroid gland

a part of the cell-mediated immune response

106
Q

What TSH, T3, & T4 levels are seen in endemic colloid goiter? Describe how iodine deficiency can cause this.

A

High TSH
Low T3 & T4
Iodine deficiency: a bunch of thyroglobulin secreted into the colloid…goiter. No T3 & T4 produced, but bunches of TSH try to make it happen.

107
Q

What are 4 things aside from dietary iodine deficiency that can cause endemic colloid goiter?

A

Deficiency of Iodide Trapping Mechanism
Deficiency Peroxidase System
Deficient coupling of iodinate tyrosines in thyroglobulin
Deficiency of the deiodinase enzyme (no I recycling)

108
Q

What is another name for cretinism? What are 2 things that can cause it?

A

congenital hypothyroidism

congenital lack of the thyroid gland & dietary iodine insufficiency

109
Q

When do the symptoms of congenital hypothyroidism first appear? What are they?

A

a few weeks after birth b/c they were depending on mom’s thyroid hormones
sluggish movements
retarded physical & mental development
short, stocky appearance (b/c skeletal muscle is more retarded than soft tissue growth)

110
Q

What is the treatment for Cretinism?

A

daily oral thyroxine & iodide replacement

need to begin soon after discovered before damage becomes permanent, critical time window.

Block 3; Week 6 Michelle (5 decks)

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