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Unit 2 Phys II > L15+16: Thyroid gland > Flashcards

L15+16: Thyroid gland Flashcards

1
Q

the thymus recieves ____ of total blood flow and entire cardiac output in ____

A

2% of total blood flow

1 hour

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2
Q

at what age is hypothalamus pituitary thyroid axis functional and begin secreting TH

A

12 weeks

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3
Q

cretinism

A

TH deficiency during gestation

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4
Q

functional unit of the thyroid

A

follicular cell

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5
Q

lumen contains ____ which ______

A

colloid

storage site for hormones

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6
Q

thyroglobulin

A

found in the colloid, contains thyroid HH in synthesis

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7
Q

found in the thyroid and release calcitonin

A

parafollicular cells

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8
Q

hyperthyroid

A

colloid is being reabsorbed

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9
Q

hypothyroid

A

decreased colloid reabsorption and thyroid hormone synthesis

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10
Q

hormone that causes thyrotrophs to release TSH

A

thyrotropin-releasing hormone

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11
Q

thyroid hormone synthesis and release is under feedback control of the

A

hypothalamic pituitary thyroid axis

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12
Q

TSH release causess

A

TSH is transported to the thyroid gland, binds TSH receptor on follicular cell –> stimulation of all steps in thyroid hormone synthesis

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13
Q

TSH receptor location

A

basolateral membrane of follicular cell

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14
Q

Synthesis of T3 and T4 occurs in _______ and is both _______

A

cytosol of follicular cell and colloid

intracellular and extracellular

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15
Q

T4 is

A

the major product of synthesis

a prohormone

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16
Q

converts T4 to T3 in the periphery

A

peripheral deiodinases

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17
Q

deactivate thyroid hormones

A

peripheral deiodinases

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18
Q

iodide comes from

A

diet

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19
Q

TSH stimulates

A
  1. Na+ iodide symporter
  2. thryoglobulin
  3. thyroid peroxidase
  4. T3 and T4 synthesis
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20
Q

thyroglobin (Tg)

A

glycoprotein that serves as a scaffold for tyrosine iodination, and thyroid hormone storage
has 132 tyrosine residues
produced in the cytosol of the follicular cell, contains in vesicles, and transferred to the apical membrane for thyroid hormone synthesis

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21
Q

thyroid peroxidase

A

oxidation of iodide and its incorportion into tyrosine residues to thyroglobin

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22
Q

Daily intake of iodide

A

400 ug

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23
Q

plasma pool of iodide

A

250-750 ug

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24
Q

total iodide content of the thyroid

A

7500 ug

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25
Q

form of iodide in the thyroid

A

iodithyronine/thyronines

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26
Q

amount of iodide taken up by the thyroid from the plasma

A

80 ug

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27
Q

amount released as HI or free

A

70-80 ug

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28
Q

HI=

A

hormone-associated iodine

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29
Q

what protects from iodide deficiency for about 2 months

A

large ratio of iodide in the form of hormone: amount turned over daily
100:1

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30
Q

tyrosine comes from

A

endogenous

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31
Q

iodide uptake in the follicular cells occurs by

A

Na+ iodide symporter (NIS) on basal surface

2 Na+/1 iodide

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32
Q

Na+ moves down its concentration gradient which is maintained by

A

Na+/K+ ATPase

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33
Q

how does iodide reach the colloid for production of thyroid hormones

A

Anoctamin-1 iodide channel on the apical membrane

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34
Q

TSH effects on anoctamin-1

A

opens the channel facilitating leak of iodide into the colloid

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35
Q

Low iodide diet effects to keep T3/T4 normal

A

NIS is increased

Kidneys reduce iodide excretion

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36
Q

mutations in NIS or iodide absent from diet cause

A

hypothyroidism

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37
Q

goiter occurs due to

A

lacking iodide–> enhanced TSH activity having a tropic effect

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38
Q

lack of iodide causes

A

loss of feedback control, effects of TSH go unopposed

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39
Q

feedback control in the thyroid occurs due to

A

T3/T4 negative feedback at the hypothalamus

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40
Q

congenital iodide transport defect (ITD)

A

hypothyroidism
goister
reduced uptake of radioactive iodide

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41
Q

other characteristics of NIS

A

expressed in gastric mucosa, placenta, and lactating mammary gland for iodide uptake
concentrates iodide in milk in lactating gland
not under control of TSH

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42
Q

Grave’s disease

A

autoantibodies are produced against TSH receptor and NIS

bind and stimulate growth of gland

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43
Q

Grave’s disease causes

A

hyperthyroidism

goiter caused by TSH stimulation

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44
Q

Radioactive iodine uptake (RAIU)

A

uses tracer dose of 123^I to measure uptake by gamma detection

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45
Q

reflects the activity of the thyroid gland

A

NIS

46
Q

normal RAIU

A

15% after 6 hours

47
Q

Organifaction defect

A

when iodine cannot be incorporated inoto tyrosine

48
Q

perchlorate

A

inhibits NIS

49
Q

transports iodide to the apical membrane and secretes it into the follicular lumen

A

pendrin

50
Q

thyroid peroxidase

A

oxidizes iodide to iodine at the apical luminal membrane

51
Q

oxidizing agent used by thyroid peroxidase

A

H2O2

52
Q

pendrin belongs to the solute carrier family

A

SLC26A family

53
Q

where else pendrin is expressed

A

inner ear, important in endocochlear potential and structural development

54
Q

Pendred syndrome

A

high heterogeneity/variability in mutations of pendrin:
goiter during childhood
hearing loss

55
Q

low iodide diet + pendred syndrome

A

goiter and overt hypothyroidism

56
Q

in the colloid, iodine attaches to

A

a tyrosine on Tg

about 20% are iodinated, 5% will become active thyroid hormone

57
Q

tyrosine + 1 iodide

tyrosine + 2 iodides

A

monoiodotyrosine (MIT)

diiodotyrosine (DIT)

58
Q

wolff chaikoff effect

A

iodine metabolism within the cell regulated independently of TSH
increased concentration of intrathyroidal iodide inhibits organification temporarily

59
Q

how to make T4

A

2 diiodotyrosine are coupled

60
Q

how to make T3

A

couple monoiodotyrosine and diiodotyrosine

61
Q

when are Tg/T3/T4 no longer stored in the colloid

A

upon stimulation of TSH

62
Q

enzymatically couples MIT and DIT to form T3 and T4

A

thyroid peroxidase

63
Q

megalin

A

how follicular cells engulf colloid contains Tg, T3, T4

64
Q

lysosomes

A

target the engulfed colloid

65
Q

protesases

A

split T3 and T4 from thyroglobin, which then diffuse into blood

66
Q

intrathyroidal deoiodinase

A

deiodinates excess MIT and DIT

67
Q

Tg levels in plasma

A

small amount leaks out normally

higher in hyperthyroidism

68
Q

inhibitors of iodide uptake

A

perchlorate, thiocyanate

69
Q

inhibitors of oxidation of iodide, organification, coupling

A

propylthiouracil

70
Q

bind to T3 and T4

A

** thyroxine binding globulin (TBG) **
albumin
transthyretin
lipoprotein

71
Q

T4 structure

A

2 iodines on both inner and outer rings

72
Q

T3 structure

A

2 iodines on inner ring, 1 on 3’ of outer ring

73
Q

rT3 structure

A

2 iodines on outer ring, 1 on 3’ of inner ring

74
Q

T4 is converted to T3 or rT3 by

A

deiodinase enzymes

75
Q

deiodinates inner ring of T4 to produce inactive rT3

A

deiodinase type 3

76
Q

deiodinates outer ring of T4 to produce active T3

A

deiodinases type 1 and 2

77
Q

deiodinates T3 to produce T2

A

deiodinase type 3

78
Q

deiodinates rT3 to produce T2

A

deiodinases type 1 and 2

79
Q

excretion of thyroid hormones

A

increased solubility by hepatic conjugation to sulfo/glucuronide

80
Q

2 effects of thyroid hormones

A
  1. genomic effects: gene transcription

2. nongenomic effects: acute, do not require transcriptions

81
Q

nongenomic effects

A

mostly exerted by T3: rapid effects on ion fluxes (mostly CV): stimulate

  1. Ca++ ATPase at plasma membrane and SR
    - released Ca+, inotropic, increased CO
  2. Na+/H+ antiporter in muscle
  3. O2 consumption
82
Q

transporter that shows a preference for T4

A

OATP

83
Q

transporter that shows a preference for T3

A

MCT

84
Q

MCT8 gene mutations

A

associated with psychomotor retardation and thyroid hormone resistance

85
Q

transporters for thyroid hormones (4)

A
  1. NTCP
  2. OATP
  3. LAT
  4. MCT
86
Q

NTCP

A

Na+ taurochlorate contransporting peptide

87
Q

OATP

A

Organic anion transporting polypeptide

-Na+ independent

88
Q

LAT

A

L and T type amino acid transporters

89
Q

MCT

A

monocarboxylate transporters

90
Q

Thyroid hormone receptor is found

A

intracellularly

associated with thyroid response element (TRE) gene promotor region

91
Q

binding of thyroid hormone to THR

A

regulates transcription of TRE

92
Q

THR has a greater affinity for

A

T3: 10x more

90% of response initiated by T3

93
Q

calorigenic actions of thyroid hormones

A

increased basal metabolic rate
increased body temperature
increased oxygen consumption

94
Q

mechanism of calorigenic actions of thyroid hormones

A

increasing activity of Na+/K+ ATPase

95
Q

Tissues where calorigenic effects of thyroid hormones do not occur

A

brain
gonads
spleen

96
Q

Metabolic effects of thyroid hormones

A

increased glucose absorption from gut
increased gluconeogenesis, lipolysis
increased protein synthesis and proteolysis (futile cycling)
Net degradation of tissue protein: negative nitrogen balance

97
Q

Cardiovascular effects of thyroid hormones

A

mediated by T3
Increased CO, ventilation
chronotropic, inotropic
reduced vascular resistance

98
Q

Sympathetic nervous system effects of thyroid hormones

A

Heterologous up regulation

increased synthesis of B receptors in cardiac/skeletal muscles, adipocytes

99
Q

hypothyroid children will have

A

delays in bone development, heigh, and mental health that can be attenuated with early thyroxine treatment

100
Q

Thyroid hormones and growth

A

act synergistically with growth hormone

promote bone formation, maturation of CNS, axonal growth, myelination

101
Q

2 negative feedback mechanisms for thyroid hormone release

A
  1. T3 inhibits TRH release in hypothalamus
  2. T3 down regulates TRH on thyrotrophs
    - T4 converted to T3 also downrgulates
102
Q

T4 is converted to T3 in negative feedback pathways by

A

T4 pituitary deiodinase

5’, type 2

103
Q

Hypothyroid

A

decreased carbohydrate, protein, lipid metabolism
Increased serum cholesterol
Normal levels of serum catecholamines

104
Q

Hyperthyroid

A

increased carbohydrate, protein, lipid metabolism
Decreased serum cholesterol
Normal levels of serum catecholamines BUT increased sensitivity to them due to up-regulation of B receptors

105
Q

Adult onset hypothyroidism aka

A
  1. Thyroiditis

2. Hashimoto’s

106
Q

Hyperprolatinemia

A

occurs with hypothyroidism, low T3/T4 increases TRH secretion, which increases prolactin synthesis

107
Q

Goiter is always present with

A

Hyperthyroidism

+/- hypothyroidism, so don’t make any assumptions

108
Q

Cardiovascular effects of hyperthyroidism

A

High pulse rate and increased CO

-these are to offset decreased PVR?

109
Q

Hyperthyroidism aka

A

Graves disease

110
Q

Hyperthyroidism treatment

A
  1. removal
  2. Radioactive 131^I destroys gland
  3. B blockers
  4. Propylthiouracil: decreases T4 to T3 conversion

Unit 2 Phys II (11 decks)

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