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Physiology > Lecture 14: Thyroid Gland > Flashcards

Lecture 14: Thyroid Gland Flashcards

1
Q

Where is the thyroid gland located

A

below Larynx alongside trachea

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2
Q

What is the follicule

A

The functional units of the thyroid gland, composed of spheres filled with colloid surrounded by a single layer of folluicular cells

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3
Q

What is thyroglobulin

A

Glycoprotein rich in tyrosine, is the main component of colloid

Harbors thyroid hormones at various stage of synthesis

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4
Q

What are the two endocrine cells of the thyroid gland

A

Follicular and C cells

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5
Q

What are follicular cells

A

Major secretory cells at various stages of thyroid hormone synthesis. They surround the follicles

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6
Q

What are C-cells

A

Cells that secrete calcitonin and are important for Ca2+ balance

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7
Q

What type of hormone is thyroid hormone

A

Amine, made from two tyrosine molecules with three or four iodine molecules

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8
Q

Iodine is converted to ___ and transported to thyroid gland

A

Iodide

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9
Q

Are thyroid molecules hydrophobic or hydrophilic

A

Hydrophobic

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10
Q

Why is storage of this hormone important

A

Iodine is of dietary origin so may vary and it is needed to form the thyroid hormone

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11
Q

How much thyroid hormone does the thyroid gland store

A

Enough for 3-4 months

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12
Q

What is the HPT axis

A

Regulates thyroid gland function, thyroid gland growth and T3/T4 synthesis

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13
Q

Where is thyrotropin releasing hormone released from and what does it stimulate

A

Released from hypothalamus and stimulates release of thyroid stimulating hormone from pituitary thyrotropes

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14
Q

TSH stimulates the release of

A

T3 and T4

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15
Q

How is the HPT axis regulated

A

Negative feedback of the thyroid hormone at the hypothalamus and anterior pituitary

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16
Q

HPT axis is regulated by ___ rhythm

A

Diurnal

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17
Q

The HPT axis requires dietary intake of what

A

Iodine

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18
Q

Describe how release of TRH can be used to measure ACTH in horses who potentially have Cushing’s

A

Pituitary adenoma cells lose receptor specificity for hypothalamic releasing and usually TRH will stimulate release of the corticotrophs in the pars intermedia to release ACTH

Measure at t=0, 0, 30 minutes

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19
Q

T3 or T4: rapid action and degradation, 10x more binding affinity, metabolically active, signaling form

A

T3

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20
Q

T3 or T4: slow to respond, slow to bind receptors, less active, is the blood transport form

A

T4

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21
Q

What is the precursor for thyroid hormone synthesis

A

Tyrosine

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22
Q

During thyroid hormone synthesis, iodides are attached to two tyrosine to create what two different molecules

A

Monoiodothyrosine (MIT) and diiodothyrosine (DIT)

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23
Q

During thyroid hormone synthesis: what coupling reactions take place to make T3 and T4

A
  1. MIT + DIT—> T3
  2. DIT + DIT—> t4
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24
Q

What is the first step in thyroid hormone synthesis

A

Thyroglobulin is synthesized in follicle cells and exocytosed to colloid

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25
Q

The second step of thyroid synthesis involves ___ being transported by secondary active transport Na+/K+ ATPase

A

Iodide

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26
Q

what is iodide trapping

A

All iodide in body is concentrated in thyroid

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27
Q

Step 3 of thyroid hormone synthesis involves the oxidation of iodide to active iodide by what enzyme

A

Thyroperoxidase (TPO)

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28
Q

In thyroid hormone synthesis the activated iodide exit through channels into the ___

A

Colloid

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29
Q

After activated iodide molecules exit into colloid, tyrosine iodination in the colloid occurs. What does that involve

A

Iodides in the colloid are quickly attached by thyroperoxidase to tyrosine molecules within the Tg molecule

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30
Q

What is the perioxidase coupling reaction during thyroid hormone synthesis that results in T3 and T4

A

Syntheses of thyroid hormone from MIT and DIT, peroxidase coupling of MIT and DIT with Tg molecule

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31
Q

DIT + DIT forms what form of thyroid hormone

A

T4 (thyroxine)

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32
Q

MIT + DIT forms what form of thyroid hormone

A

T3 (tri-iodothyronine)

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33
Q

After Tg-thyroid hormone complex is created where is it taken

A

Into follicular cell by phagocytosis

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34
Q

What must occur after Tg-thyroid is phagocytosed into follicular cell in order to make active T3 and T4

A

Lysosomes cleave Tg-complex

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35
Q

After cleavage of Tg-complex by lysosomes what happens to the lipophilic thyroid hormones

A

Diffuse through plasma membrane into circulation

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36
Q

What happens to leftover MIT’s and DIT’s after thyroid hormone synthesis

A

They are of no use
Storage form

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37
Q

What happens to iodide after thyroid hormone synthesis is complete

A

Unused iodide is cleaved from MIT and DIT by follicular deiodinase and returns to colloid

38
Q

What does thyroid binding globulin bind

A

75% of T3/T4

39
Q

What species have almost no thyroid binding globulin

A

Rabbits and guinea pigs

40
Q

What does transthyretin bind

A

10% T4

41
Q

Where does transthyretin transport T4 to

A

Secreted into cerebral spinal fluid and allows transport to nervous system

42
Q

What does albumin bind

A

15% t4 and 25% t3

43
Q

What percent of T4/T3 is free

A

1%

44
Q

What organ only excretes free T3/T4

A

Kidney

45
Q

What is the half life of T3

A

1 day

46
Q

What is the half life of T4

A

7 days

47
Q

What hormone fraction is important for thyroid hormone signaling and HPT feedback

A

Circulating free hormones

48
Q

What hormone fraction of thyroid hormone allows for a serum reserve capacity

A

Bound hormones

49
Q

Deiodinase cleaves iodine groups to make active T3 and T4, at what carbon is active T3 cleave

A

Carbon 5 of the outer ring

50
Q

What organs does active T 3 go to

A

Liver and kidney

51
Q

Deiodinase cleaves iodine groups to make active t3 and T4, at which carbon is the iodide removed to create reverse T3

A

Carbon 4 of inner ring

52
Q

Where is type I deiodinase found

A

Liver, kidney, thyroid

53
Q

Where is type II deiodinase found

A

Brain, pituitary, brown fat, thyroid, placenta, striated muscle

54
Q

Where is type III deiodinase found

A

Brain, placenta, skin

55
Q

Which deiodinase promotes thyroid signaling and which one inhibits

A

Deiodinase II promotes
Deiodinase III inhibits

56
Q

What is the main effect of T3/T4

A

Regulate metabolic rate

57
Q

How does direct regulation of thyroid hormone occur

A

Thyroid hormone binds to AdNT in inner mitochondrial member and, AdNT exchanges free ATP with ADP across inner mitochondrial membrane where it binds T3R receptor on mtDNA

58
Q

How does the indirect regulation of T3 work

A

T3 binds T3R in nuclear genome, nuclear genes like NRF and PGC-1 influence mitochondrial biosynthesis include RNA polymerase mitochondria and mitochondrial transcription factor A

RNA polymerase and Mitochondrial transcription factor A will for to mtDNA along with thyroid hormone bound to T3R

59
Q

What do thyroid hormone receptors bind on DNA

A

Thyroid response element

60
Q

Unbound thyroid hormone receptor interacting with TRE leads to ___

A

Repression of the transcription through a co-repressor protein

61
Q

The bound thyroid hormone receptor complex interacting with TRE leads to ____

A

Activation of transcription through coactivator proteins

62
Q

How does T3 bound receptors affect Na+K+ ATPase

A

Stimulate/increase Na+/K + ATPase which increases O2 consumption, increased basal metabolic rate

63
Q

How does T3 bound receptors impact uncoupling proteins

A

Increase uncoupling protein—> enhanced fatty acid metabolism and heat production without ATP synthesis

64
Q

How does T3 bound receptor impact protein synthesis and degradation

A

Enhancing growth and differentiation with a net increase in catabolism

65
Q

How does T3 bound receptors impact the liver

A

Liver opposes insulin by stimulating glucogenesis and glycogenolysis, acts synergistically with peripheral tissues to with insulin to facilitate glucose uptake

66
Q

How does t3 bound receptors impact catecholamine receptors

A

Increase catecholamine receptors, enhancing effects of SNS

67
Q

How does T3 bound receptors impact cholesterol

A

Increases cholesterol synthesis and LDLR regulation

68
Q

What is the physiological effect of thyroid hormone on liver

A

Regulates triglyceride and cholesterol metabolism , lipoprotein metabolism

69
Q

What is the physiological effect of thyroid hormone on bone

A

Increases bone maturation, promotes epiphyseal plate closure

70
Q

What is the physiological effect of thyroid hormone on adipose tissue

A

Induces adipose tissue differentiation, lipid mobilization and storage, and thermogenesis

71
Q

What is the physiological effect of thyroid hormone on cardiovascular system

A

Increases CO, increases blood following, decreases resistance

72
Q

What is the physiological effect of thyroid hormones on pituitary

A

Regulates synthesis of pituitary hormones, stimulates GH and inhibits TSH

73
Q

What is the physiological effect of thyroid hormone on the brain

A

Necessary for nerve atonal cell growth and devleopmen; controls expression of genes with associated myelnation and cell differentiation, migration

74
Q

Hyper or hypothyroidism: increased HR, increased Cardiac contractility, increased cardiac output

A

Hyperthyroidism

75
Q

Hyper or hypothyroidism: decreased heart rate, decreased cardiac contractillity, decreased CO

A

Hypothyroidism

76
Q

Hyper or hypothyroidism: Increased vascular resistance, decreased RBF, decreased B-adrenergic receptor sin kindey

A

Hypothyroidism

77
Q

Hyper or hypothyroidism: decreased RAAS, decrease filtration pressure, decrease GFR

A

Hypothyroidism

78
Q

Hyper or hypothyroidism: increased RAAS, increased filtration pressure, increases GFR

A

Hyperthyroidism

79
Q

Hyper or hypothyroidism: increased TGF, increased tubular mass, increased Na/k+ ATPase and decreased ability to concentrate urine

A

Hyperthyroidism

80
Q

Hyper or hypothyroidism: decreased TGF, decreased tubular mass, decreased Na/K ATPase, decrease NHE activity, decreased urinary concentrating ability

A

Hypothyroidism

81
Q

Clinical case: weight loss in feline- owner complained pet showed weight loss over 6 months, matted fur, Temp=103, owner reports healthy appetite and high activity: what is initial diagnosis and what could lead to increase temperature

A

Diagnosis: hyperthyroidism
Temp increase: increased basal metabolism

82
Q

Clinical Case: weight loss feline cont. blood work shows T4=52nmol/L (normal: 1.3-32.3). MRI of head is unremarkable. What is most likely origin of hyperthyroidism

A

Primary hyperthyroidism- overactive thyroid gland

83
Q

In HPT axis how does primary hyperthyroidism affect release of upstream hormones

A

Since thyroid gland is overactive and not due to overstimulation from hypothalamus or anterior pituitary, the hyperthyroidism will cause increased negative feedback on anterior pituitary, decreasing release of TSH

84
Q

Clinical case: goiterism and failure to thrive: farmer complains of failure to thrive, prolonged gestation, kids born hairless and stunted growth. Also observe mass on neck. Pasture has abundant rapeseed, white clower and sparse grass. What is initial diagnosis and what is cause

A

Diagnosis: hypothyroidism
Cause: thioglycosides in rapeseed will cause dietary iodine deficiency because it blocks uptake of iodine in gut.

85
Q

Clinical case: goieterism and failure to thirve in kids cont: what could have causes the presence of goiter in kids

A

Goitrin is compound excreted in milk or passed in utero on to offspring which can cause mass and hypothyroidism

86
Q

What explains the presence of goiters in HPT axis

A

Goiters is a result of lack of negative feedback from thyroid hormones, so no negative feedback via T3/T4, which will cause increased secretion of TSH and enhance growth of thyroid gland

87
Q

Does the following situation cause goiters: hypothyroidism caused by primary failure of thyroid gland, decreased T3 and T4 levels, increased TSH. Is a goiter present and why

A

Yes, primary impact to thyroid gland so unable to secrete t3/t4 to act in negative feedback loop to anterior pituitary, so increase TSH released onto thyroid gland causing increased growth of gland

88
Q

Does the following situation cause goiters: hypothyroidism, anterior pituitary defiancy, decreased T3/T4, decreases TSH and/or decreases TRH. Is a goiter present, why or why not?

A

No goiter, anterior pituitary deficiency means it can’t release TSH. (increased TSH correlates with presence of goiters

89
Q

Will the following situation causer a goiter to be present: hypothyroidism caused by iodine deficiency. Decreased T3/T4 and increased TSH. Is a goiter present, why or why not

A

Yes, because iodine is only needed to make t3/t4 not needed to release TSH from anterior pituitary so we have excess release of TSH on thyroid gland without negative feedback from t3/t4 therefore enhanced growth of thyroid

90
Q

Would the following situation cause a goiter: hyperthyroidism caused by thyroid-stimulating immunoglobulin: Graves’ disease, increase T3/T4, decreased TSH. Is a goiter present, why or why not

A

Yes, only scenario where goiter is present and TSH is low because thyroid stimulating immunoglobulin acts like TSH therefore enhancing growth of thyroid

91
Q

Would the following situation cause goiters: hyperthyroidism cause by excess pituitary function, ex: thyrotroph adenoma, increased T3/T4 and increased TSH and/or TRH. Is a goiter present, why or why not

A

Yes because tumor causes insuppressible release of TSH from pituitary onto thyroid that is not stopped by negative feedback loop so increase TSH will enhance growth of thyroid gland

92
Q

Does the following situation cause goiters: hyperthyroidism caused by hypersecreting thyroid hormone, increased T3/T4 and decreased TSH

A

No because only thyroid gland is implicated not any upstream signaling so won’t cause increase in TSH, if anything will cause a decrease in TSH release

Physiology (10 decks)

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