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+ CAPS 301: Respiratory, Renal, GI, Endocrinology, Reproduction > Thyroid Gland > Flashcards

Thyroid Gland Flashcards

1
Q

Where is the thyroid gland?

A

in anterior neck, on trachea just inferior and lateral to thyroid cartilage of larynx

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2
Q

Does the thyroid gland receive higher or lower blood flow per unit weight than kidneys?

A

higher

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3
Q

How many lobes does the thyroid gland have?

A

2 – left and right

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4
Q

What are the lobes of the thyroid gland connected by?

A

isthmus (median tissue mass)

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5
Q

What are thyroid glands composed if?

A

20 million thyroid follicles (spherical functional units)

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6
Q

What are the walls of follicles formed by?

A

follicular cells (cuboidal epithelial cells)

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7
Q

What do follicular cells produce?

A

thyroglobulin (TGB)

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8
Q

What is thyroglobulin (TGB)?

A

glycoprotein containing about 130 tyrosine amino acids

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9
Q

What does the lumen of each follicle do?

A

stores gelatinous colloid made primarily of TGB

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10
Q

What do C (parafollicular) cells do?

A

responsible for secretion of calcitonin

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11
Q

What is calcitonin?

A

hormone involved in calcium homeostasis

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12
Q

What are thyroid hormones?

A

iodinated thyronines and are called:

  • tetraiodothyronine (thyroxin or T4)
  • triiodothyronine (T3)
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13
Q

What is the structure of T4?

A

two tyrosine amino acids linked together + 4 iodines

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14
Q

What is the structure of T3?

A

two tyrosine amino acids linked together + 3 iodines

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15
Q

Describe the amount of T4 vs. T3.

A
  • more than 90% of TH released from thyroid gland is T4

- but almost all of it is eventually converted to T3 in target tissues

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16
Q

What are the functions of plasma membranes of epithelial cells?

A

different functions depending on location:

  • exposed to lumen – apical surface
  • exposed to interstitial space – basolateral surface
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17
Q

What are the general steps of thyroid hormone synthesis?

A
  1. formation and storage of TGB
  2. iodide trapping and oxidation to iodine
  3. iodination
  4. coupling
  5. colloid pinocytosis
  6. proteolysis
  7. secretion and recycling
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17
Q

What are the general steps of thyroid hormone synthesis?

A
  1. formation and storage of TGB
  2. iodide trapping and oxidation to iodine
  3. iodination
  4. coupling
  5. colloid pinocytosis
  6. proteolysis
  7. secretion and recycling
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18
Q

Thyroid Hormone Secretion – 1. formation and storage of TGB

Where is TGB gene?

A

long arm of chromosome 8

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19
Q

Thyroid Hormone Secretion – 1. formation and storage of TGB

What happens in this step?

A
  • translation of TGB mRNA in RER of follicular cells – nucleus
  • protein is glycosylated in Golgi apparatus, packaged into vesicles and released by exocytosis into lumen of follicle to become a major component of the colloid
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20
Q

Thyroid Hormone Secretion – 2. iodide trapping and oxidation to iodine

What happens in this step?

A
  • follicular cells accumulate iodide (or iodine ions) from blood
  • uptake of I- into cell is Na+ K+ ATPase-dependent
  • SECONDARY ACTIVE TRANSPORT: uptake of I- into cell by Na+/I- symporter (NIS or iodide trap) – co-transports 1 I- with 2 Na+ across basolateral membrane into cell
  • iodide diffuses across follicular cell
  • FACILITATED DIFFUSION: transported across apical membrane into colloid by pendrin (chloride-iodide ion counter-transporter)
  • iodide is also oxidized to iodine by thyroid peroxidase (TPO)
    result: iodide in colloid
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21
Q

Thyroid Hormone Secretion – 3. iodination

What happens in this step?

A
  • within the colloid, TPO catalyzes immediate binding of iodine with 10-12 tyrosine amino acids on each TGB
  • each tyrosine can interact with either: one iodine to form monoiodotyrosine (MIT) OR two iodines to form diiodotyrosine (DIT)
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22
Q

What is monoiodotyrosine (MIT)?

A

tyrosine + one iodine

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23
Q

What is diiodotyrosine (DIT)

A

tyrosine + two iodines

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24
Q

Thyroid Hormone Secretion – 4. coupling

What happens in this step?

A

internal rearrangement within TGB links MITs and DITs in a highly specific fashion:

  • coupling of two DITs results in T4
  • coupling of MIT and DIT produces T3
  • coupling can occur within a single molecule, or between different molecules of TGB
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25
Q

Thyroid Hormone Secretion – 4. coupling

Coupling of what results in T4?

A

two DITs

26
Q

Thyroid Hormone Secretion – 4. coupling

Coupling of what produces T3?

A

MIT and DIT

27
Q

Thyroid Hormone Secretion – 4. coupling

Why is T4 the main product?

A

because coupling of two DITs is more frequent

28
Q

Thyroid Hormone Secretion – 4. coupling

Note: At this point, both thyroid hormones are still attached to…..

A

TGB molecules, and stored in colloid

29
Q

Thyroid Hormone Secretion – 5. colloid pinocytosis

What happens in this step?

A

small droplets of colloid (endosomes) containing iodinated thyroglobulins enter follicle cells by endocytosis, and combine with lysosomes to form endolysosomes

30
Q

Thyroid Hormone Secretion – 6. proteolysis

What happens in this step?

A

lysosomal enzymes within endolysosomes release T3 and T4, and MITs and DITs, from thyroglobulin molecules

31
Q

Thyroid Hormone Secretion – 7. secretion and recycling

What happens in this step?

A
  • free T3 and T4 diffuse through basal membrane out of follicular cell and into vast network of capillaries surrounding the follicles
  • MITs and DITs are hydrolyzed by cytoplasmic deiodinase enzyme to tyrosine amino acids and iodine ions, which are then recycled within the follicular cell
32
Q

What do all steps in synthesis of thyroid hormones require?

A

TSH

all steps require – including expression of TGB and TPO genes, NIS action, and iodination of TGB

33
Q

What does 99.5% of T3 and T4 do upon entering blood?

A

binds immediately with several plasma proteins (all of which are produced by liver)

  • mainly thyroxine-binding globulin (TBG)
  • less with transthyretin
  • less with albumi
34
Q

What does 0.5% of T3 and T4 do upon entering blood?

A

remains free (does not bind) and is responsible for biologic activity

35
Q

Regulation of Biological Activity of Thyroid Hormones

What is the homeostasis of thyroid hormones (TH) regulated by? (2)

A
  • one based on hypothalamic-pituitary-thyroid (HPT) axis

- one at intracellular level

36
Q

Regulation of Biological Activity of Thyroid Hormones

Hypothalamic-Pituitary-Thyroid (HPT) Axis – Diagram

A

–

37
Q

Regulation of Biological Activity of Thyroid Hormones – Intracellular Level

What is the main hormone produced by thyroid?

A

T4

38
Q

Regulation of Biological Activity of Thyroid Hormones – Intracellular Level

Does T3 or T4 have higher affinity for TH receptor?

A

T3 possesses 100x higher affinity for TH receptor and is responsible for all biological effects

39
Q

Regulation of Biological Activity of Thyroid Hormones – Intracellular Level

How does T4 bind with TH receptors?

A

can cross plasma membranes only through cell-specific transporters

  • mutations in transporters can cause severe neurological defects in humans
  • mutations in MCT8 transporter cause severe neurologic defects in humans
40
Q

Regulation of Biological Activity of Thyroid Hormones – Intracellular Level

Where are TH receptors located?

A

in nucleus of target cells

41
Q

Regulation of Biological Activity of Thyroid Hormones – Intracellular Level

Once inside the cell, the concentration of THs is controlled by what?

A

three deiodinase enzymes (D1, D2 and D3)

42
Q

Regulation of Biological Activity of Thyroid Hormones – Intracellular Level

What does both D1 and D2 do?

A

generate T3 by removing 1 iodine from T

43
Q

Regulation of Biological Activity of Thyroid Hormones – Intracellular Level

What does D3 do?

A

serves as physiological terminator of TH activity by degrading both T4 and T3 their respective inactive metabolites

44
Q

Regulation of Biological Activity of Thyroid Hormones – Intracellular Level

What accounts for T3 measured in plasma?

A

80% – deiodinase-coordinated conversion of T4 to T3 in target tissues
20% – secreted by thyroid gland

45
Q

Regulation of Biological Activity of Thyroid Hormones – Intracellular Level

What are some rapid effects by THs? (3)

A

(non-genomic effects)

  • stimulation of sugar transport
  • Ca2+ ATPase activity
  • increased Na+ transport in muscle

occur within seconds or minutes

46
Q

Regulation of Biological Activity of Thyroid Hormones – Intracellular Level

What are non-genomic effects mediated by?

A

binding to membrane receptors and activation of second messenger signaling cascades

47
Q

Physiologic Functions of Thyroid Hormones

Why are THs critically important throughout pregnancy?

A

responsible for normal brain development in fetus

48
Q

Physiologic Functions of Thyroid Hormones

What are THs important for during development and in adults?

A
  • key regulators of basal metabolic rate (minimum level of energy required to maintain vital functions at rest) in most tissues
  • critically important for normal development of nervous and skeletal systems, and maturation of reproductive system
49
Q

Physiologic Functions of Thyroid Hormones

Overall, what do THs play significant role in?

A

almost all tissues and organs in the body

50
Q

Pathology of Thyroid Hormones

Hypothyroidism – Diagram

A

–

51
Q

Pathology of Thyroid Hormones

What is the most common cause of hypothyroidism worldwide?

A

iodine deficiency

52
Q

Pathology of Thyroid Hormones

What is the most common cause of hypothyroidism in North America?

A

Hashimoto’s thyroiditis

53
Q

Pathology of Thyroid Hormones

What is Hashimoto’s thyroiditis?

A

autoimmune disorder involving anti-thyroid antibodies that block and eventually destroy thyroid function

have high levels of plasma TSH

54
Q

Pathology of Thyroid Hormones

What is TH release regulated by?

A

hypothalamus-pituitary-thyroid axis

55
Q

Pathology of Thyroid Hormones

How does the incidence of hypothyroidism change with aging?

A

increases

56
Q

Pathology of Thyroid Hormones

What are typical symptoms of hypothyroidism? (2)

A
  • thyroid gland enlargement (goiter)

- low metabolic rate resulting in intolerance to cold and weight gain

57
Q

Pathology of Thyroid Hormones

What may result in permanent decrease in psycho-neurological function?

A

genetic deficiency of fetal thyroid gland or maternal factors, such as lack of iodine in diet during pregnancy

in a newborn, symptoms include profound mental retardation and short disproportionate body

58
Q

Pathology of Thyroid Hormones

What is the most common form of hyperthyroidism?

A

Grave’s disease

59
Q

Pathology of Thyroid Hormones

What is Grave’s disease?

A

autoimmune disorder involving production of abnormal antibodies called thyroid stimulating immunoglobulin (TSI)

TSI molecules bind to TSH receptors and permanently switch them on → continuous release of thyroid hormones

low or undetectable levels of plasma TSH

60
Q

Pathology of Thyroid Hormones

What do clinical manifestations of hyperthyroidism include? (6)

A
  • formation of goiter
  • ↑ metabolic rate, resulting in intolerance to heat
  • weight loss, despite adequate food intake
  • rapid and irregular heartbeat
  • eye and skin problems also common
  • severe: exophthalmos
61
Q

Pathology of Thyroid Hormones

What is exophthalmos?

A

bulging eyes, caused by TSI antibodies binding to muscles that move our eyeballs, and connective tissues behind the eyeballs, pushing eyeballs out

62
Q

Pathology of Thyroid Hormones

Hyperthyroidism – Diagram

A

–

+ CAPS 301: Respiratory, Renal, GI, Endocrinology, Reproduction (32 decks)

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