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HRM Week 1 > Thyroid Hormone Physiology > Flashcards

Thyroid Hormone Physiology Flashcards

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1
Q

What are the parts of the sectioned thyroid?

A

Thyroid follicle, C cells, Follicular cells, Colloid, Capillaries, Capsule

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2
Q

What do C cells secrete?

A

Calcitonin

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3
Q

What do Follicular cells secrete?

A

Thyroid hormone

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4
Q

What is Colloid?

A

Glycoprotein

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5
Q

What makes up the thyroid capsule?

A

Connective tissue

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6
Q

What are follicular cells involved in?

A

Thyroid hormone synthesis

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7
Q

What does the Thyroid follicle contain?

A

Colloid which is a proteinaceous containing thyroglobulin, a glycoprotein necessary for the synthesis of thyroid hormones (T3 and T4)

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8
Q

What is the significance of Parafollicular “C” cells?

A

Produce calcitonin, important for calcium regulation.

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9
Q

What are unique characteristics of the Thyroid Gland?

A

Requires trace element, iodine. Stores thyroid hormone as a thyroglobulin complex.

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10
Q

What is TRH?

A

Thyrotropin releasing hormone

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11
Q

What is TSH?

A

Thyroid stimulating hormone

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12
Q

What are the two thyroid hormones?

A

T3 - triiodothyronine

T4 - thyroxine

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13
Q

What are other negative regulators of the Hypothalamic Pituitary Thyroid Axis?

A

Somatostatin (hypothalamic), Dopamine (hypothalamic), and high glucocorticoids (adrenal cortex) all dec. TSH release.

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14
Q

How is Thyrotropin Releasing Hormone (TRH) synthesized?

A

Translated as a preprohormone. Mature protein originally identified as a tripeptide. Now its a tetrapeptide.

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15
Q

What is the function of TRH?

A

Stimulates release of TSH from thyrotrophs of the anterior pituitary.

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16
Q

Where is TRH found?

A

Mostly hypothalamus. Also found in cerebral cortex, GI and Pancreas.

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17
Q

What is an important role of TRH?

A

Has important role in regulation of energy homeostasis, feeding behavior, thermogenesis, and autonomic regulation. TRH controls energy homeostasis mainly through stimulation of TSH and ultimately regulation of circulating thyroid hormone levels.

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18
Q

How far is TRH distributed?

A

Widely distributed in CNS and regarded as a NT or modulator of neuronal activities in extra hypothalamic regions, including cerebellum.

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19
Q

How does Thyrotropin Releasing Hormone (TRH) cause the release of TSH?

A

First TRH binds to transmembrane TRH receptors on thyrotrophs of the anterior pituitary gland. This promotes the release and synthesis of thyroid stimulating hormone (TSH).

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20
Q

What is TRH and how does it act on the cell?

A

Protein hormone. ITs receptor is in the plasma membrane. TRH receptor (Gq) is coupled to PLC (phospholipase C) and inositol triphosphate signal so changes in Ca++ are involved in signal transduction induced by TRH binding to TRH receptor. Large release in calcium stores from IP3 results in secretory vesicles fusing with the cell membrane and TSH secretion.

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21
Q

Where are TSH, FSH and LH made?

A

Anterior Pituitary

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22
Q

What is the structure of Thyroid Stimulating Hormone (Thyrotropin - TSH)?

A

28 kDa glycoprotein consisting of alpha and beta chains. Alpha chain is the same as found in other pituitary hormones, LH, FSH, and the placental hormone hCG. Beta chain is specific to TSH and confers specificity of hormonal action.

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23
Q

How does TSH-TSH receptor signal transduction work?

A

Receptors reside on plasma membrane of thyroid follicular cells. It’s a G-protien coupled receptor. TSH: TSH receptor binding stimulates many aspects of thyroid hormone synthesis and release.

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24
Q

What two products does Iodine and Tyrosine combine to make?

A

Thyroxine (T4 - 4I), Triiodothyronine (T3 - 3I).

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25
Which Thyroid hormone is more active?
T3
26
Which Thyroid hormone has a longer half life?
T4
27
How is T3 and T4 transported into the cell?
A symporter with Na+. You need a sodium gradient in order for this to occur. It's similar to Na+ glucose transporter in the kidney.
28
What are the 7 Steps of Thyroid Hormone Synthesis?
Iodide Uptake. Iodide Oxidation to Iodine. Iodination of tyrosine-thryoglobulin. Conjugation of MIT DIT thyroglobulin. Endocytosis of T3 T4 thyroglobulin. Proteolysis to mature hormone. Secretion of T3, T4.
29
What happens to T4 intracellularly?
It is converted to T3.
30
Which TH bind to thyroid hormone receptors?
Both T3 and T4 but is thought that most T4 is converted into T3.
31
Where is the thyroid receptor?
Inside the cell. T3 and T4 go through the membrane and bind in the cell.
32
What is the half life of thyroid hormones?
T3 has shorter circulating t1/2 of about 1 day. T4 is about 6 days.
33
What are the three Thyroid Hormone Carrier Proteins?
Thyroxine binding globulin (TBG, thyroid binding globulin), Transthyretin, Albumin
34
How much TH does Thyroxine binding globulin bind?
75 percent of T4 and 75 percent of T3. 1 binding site for one thyroid hormone molecule.
35
How much TH does Transthyretin bind?
Binds 20 percent of T4 and 5 percent of T3. 2 binding sites for thyroid hormones.
36
How much TH does Albumin bind?
Binds 5 percent of T4 and 20 percent of T3. Several binding sites for thyroid hormone.
37
How much of T4 and T3 is bound?
99.98 T4, 99.95 T3
38
When do serum proteins increase?
During pregnancy, estrogen or androgen treatment.
39
When do serum proteins decrease?
By hyperthyroidism, malnutrition, and nephritic syndrome (i.e., diseases that cause protein loss)
40
What is net TH?
Total hormone (bound plus free). It may fluctuate.
41
What enzyme converts T4 to T3? What can they make if the inner ring rather than outer ring is deiodinated?
Deiodinase I and II. T4 can be converted to rT3 and this causes hormone deactivation.
42
What are Deiodinases important for?
Activation and deactivation of Thyroid Hormones.
43
Where is Deiodinase I present? What is significant about it?
Highly prevalent in liver and kidney. Converts less active T4 to more active T3 so increases T3 within the cells and in the circulation. Converts T4 to rT3 for disposal. Is a drug target, Prophylthiouracil sensitive.
44
What is Deiodinase II?
Present in brain, pituitary, skeletal and cardiac muscles. Converts T4 to supply intracellular T3.
45
What is Deiodinase III?
Present in brain, skin, placenta. Deactivates the hormones.
46
What two processes does TSH stimulate in the thyroid gland?
Secretion of mature thyroid hormones and Production of new thyroid hormone batch.
47
What things get stimulated by TSH in order to produce new TH?
Thyroid peroxidase synthesis. Thyroglobulin transcription. Na+/I- transport activity (increases I- availability to the follicular cell)
48
How does T3 and T4 lead to changes in gene transcription?
First, T3T4 are bound to thyroxin binding globulin. Free T3 and T4 enter cell by diffusion or by carrier mediated transport. T4 is converted to T3. Then T3 and T4 bind THR which can dimerize with another T3:THR or with retinoid X receptor. Monomer or dimers bind thyroid response elements on thyroid responsive genes and initiate gene transcription.
49
What TH has a higher affinity to THR?
T3
50
What are the two thyroid receptors?
Alpha and beta
51
What enzyme converts T4 to T3?
5'3' monodeiodinase activity removes the 5' iodine.
52
How many different energy dependent thyroid hormone transporters have been identified in humans?
10. Ensuring that intracellular levels are higher in cells than in ECF or plasma.
53
What is Thyroid Hormone necessary for?
Normal metabolism, growth and development and virtually every tissue of the body is affected either directly or indirectly.
54
What does Thyroid Hormone promote?
Oxygen consumption, heat production and free radical formation.
55
What are the main functions of Thyroid Hormone?
Regulation of BMR. Increased heat production. Increased glucose utilization, uptake and synthesis. Permissive sympathetic side effects, Inc. heart rate, Inc. contractility.
56
Why do many states mandate newborn testing of thyroid function?
Cretinism. If hormone replacement is started within a few days of birth, growth and development will be normal.
57
What is Cretinism?
Congenital lack of thyroid hormone in infants.
58
What are the effects of Cretinism or Maternal Hypothyroidism?
Profound mental retardation, Short stature, Delay in motor development, Coarse hair, Protuberant abdomens.
59
What is the Etiology of Maternal Hypothyroidism (three causes)?
Lack of iodine in the maternal diet (very rare currently). Mother with Hashimoto's thyroiditis makes blocking anti-TSH receptor antibodies. Exposure to radioactive iodine or antithyroid drugs during pregnancy.
60
What is the US RDA for Iodine?
150 micrograms per day for both men and women.
61
What is the Tolerable Upper Intake Level (UL) of Iodine for adults?
1,100 ug/day (1.1 mg/day)
62
What are natural sources of Iodine?
Sea life, like kelp and certain seafood, as well as plants grown in iodine-rich soil.
63
What is fortified with iodine?
Iodized salt.
64
What are signs of Cretinism in newborns?
Respiratory difficulty, cyanosis, jaundice, poor feeding, horse cry, umbilical hernia, and marked retardation of bone maturation.
65
What does tibial length have to do with hypothyroidism?
Proximal tibial epiphysis and distal femoral epiphysis have certain lengths in full-term infants that weigh greater than 2.5 kg. Shorter than expected values strongly suggest hypothyroidism.
66
What if hormone replacement is delayed significantly in Cretinism?
Physical development (bone age and height) will proceed but mental development will not.
67
What are the Physiological Effects of Low Thyroid Hormone in Adults?
Slow course of symptoms. Lethargy, Somnolence, Slowed intellectual functions including speech, Stiffness and aching muscle, Cold intolerance, Delayed depp tendon reflex relaxation, Anovulation and amenorrhea common, Menorrhagia less common.
68
What are the physiological effects of Excess Thyroid hormone in adults?
Inc. HR, Inc. sensitivity to catecholamines via inc in number of beta adrenergic receptors in heart, skeletal muscle, adipose tissue and lymphocytes. Amplifies catecholamine post-receptor action. Increased O2 demand leads to increased production of EPO and increases erythropoiesis. Promotes GI motility resulting in increased defecation.
69
What effect does excess thyroid hormone have on adult bone?
Promotes bone turnover with net bone loss and hypercalciuria.
70
What effect does excess thyroid hormone have on adult muscle?
Promotes increased protein turnover and net loss of skeletal muscle with myopathy. Muscle weakness, muscle degeneration, muscle fatigue, heat intolerance. Increase in speed of muscle contractions and relaxation.
71
What effect does excess thyroid hormone have on adult glucose?
Increases hepatic gluconeogenesis and glycogenolysis and intestinal glucose absorption, therefore can worsen control of glucose levels with diabetes patients.
72
What effects does excess thyroid hormone have on cholesterol?
Increase in LDL receptor number and thereby accelerates LDL clearance. (total LDL cholesterol levels are typically elevated with hypothyroidism)
73
What effects does excess thyroid hormone have on sex hormones?
Alters the production, responsiveness and metabolic clearance of several hormones. Can cause precocious puberty. Promotes aromatization of androgens to estrogens and inc sex hormone binding globulins which can contribute to gynecomastia. Impairs GnRH and regulation of ovulation causing infertility.
74
What is Thyrotoxicosis?
Refers to any cause of excessive thyroid hormone concentration and its effect on organ systems.
75
In the spectrum of endocrine emergencies, what ranks as one of the most critical illnesses?
Thyroid storm
76
What is Thyroid storm?
Represents extreme manifestation of thyrotoxicosis.
77
What drugs are used to treat Thyroid storm?
Beta adrenergic blockers, Thioamides (antithyroid), Corticosteroids (to cover for functional hypoadrenalism induced by thyrotoxicosis)
78
What is the incidence of thyroid storm?
Less than 10 percent of patients hospitalized for thyrotoxicosis. Mortality ranges from 20 to 30 percent.
79
What is Primary hypothyroidism?
Problem lies in thyroid gland. Can be due to congenital defects, Gland destruction (surgical, radioactive, external radiation), Iodine deficiency, Autoimmune (Hashimoto thyroiditis - chronic lymphocytic thyroiditis)
80
What happens to TRH, TSH and TH levels in primary hypothyroidism?
TH levels dec. TSH and TRH levels inc.
81
What is Hashimoto thyroiditis?
Antibodies react against proteins in the thyroid gland followed by immune mediated gland destruction.
82
What is Secondary or tertiary hypothyroidism?
Problem lies in pituitary gland or hypothalamus (respectively). Usually associated with other pituitary deficiencies.
83
What happens to TRH, TSH and TH levels in Secondary or tertiary hypothyroidism?
TRH levels inc, TSH and TH levels dec.
84
What happens to TRH, TSH and TH levels in thyroid hormone resistance syndromes (with normal hormone production)?
TRH, TSH and TH all inc.
85
What is Thyrotoxicosis?
Hyperthyroidism tha tresults in toxicosis in target tissues.
86
What is Graves' disease?
Production of thyroid stimulating immunoglobulins (TSI). T cells become sensitive to thyroid antigen and stimulate B cells to produce Abs that mimic TSH. Result is hyperstimulation of thyroid hormone production. IgG can cross placental membranes and affect fetus.
87
What happens to TRH, TSH and TH levels in this scenario?
TH inc. TRH and TSH both dec.
88
What has uncontrolled maternal hyperthyroidism (Graves) associated with?
Fetal tachycardia, small for gestational age babies, prematurity, stillbirths, and possibly congenital malformations.
89
When can goiter develop?
Its an enlarged thyroid gland. Can manifest with hypo- or hyperthyroidism. Develops most often in patients distant from ocean.
90
What causes the gland to enlarge in goiter?
Trophic TSH stimulus in hypothyroidism. Trophic thyroid stimulating immunoglobulins in hyperthyroidism

HRM Week 1 (11 decks)

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