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Physio > Body Metabolism: Thyroi Hormones > Flashcards

Body Metabolism: Thyroi Hormones Flashcards

1
Q

Which thyroid lobe is larger?

A

Right

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2
Q

What is colloid primarily made up of?

A

Thyroglobulin

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3
Q

Parafollicular cells

A

. Located in thyroid gland btw follicles and synthesize calcitonin

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4
Q

Dietary iodine

A

. Most important source for replenishment of extracellular iodide taken for thyroid hormone synthesis from extracellular fluid
. Usually organic iodine that is converted to iodide in GI tract prior to absorption and entry into ECF
. 20% is removed from extracellular fluid by thyroid gland
. 80% is freely filterable at glomerulus then some is passively reabsorbed and the rest is excreted in urine

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5
Q

Intake of iodide into thyroid

A

. Transported through Na/I cotransporter (NIS) fueled by Na driving force
. TSH stimulates this
. Most iodide in gland is utilized in thyroid hormone synthesis but some does diffuse back into circulation
. Iodide leaves cell and enters follicular lumen across apical membrane via pendrin protein

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6
Q

NIS blockers

A

. Thiocyanate and perchlorate

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7
Q

Relationship btw iodide content in thyroid and activity of iodide trap

A

. Inverse relationship

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8
Q

Thyroglobulin

A

. Large glycoprotein synthesized by thyroid follicular cells
. Released via exocytosis into colloid
. Contains 100 Tyr residues but only a few are subject to iodination

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9
Q

Thyroid hormone synthesis on thyroglobulin

A

. Iodide oxidized by thyroid perioxidase (TP) using H2O as substrate
. Thyroglobulin enters follicular lumen via exocytosis and its Tyr react w/ oxidized iodide to attach it to thyroglobulin forming 3-monoiodo-tyrosine (MIT)
. Second iodination forms 3,5-diiodotyrosine (DIT)
. 2 DIT molecules then oxidatively coupled by TP to form iodothyronine/thyroxine (T4)
. MIT and DIT coupling on thyroglobulin form T3 but it is small amt
. T3 and T4 remain attached to thyrglobulin during this

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10
Q

What stimulates thyroid peroxidase?

A

. Stimulates by TSH

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11
Q

Thyroid synthesis relationship w/ extracellular iodide

A

. Biphasic relationship
. Wolf-Chaikoff effect
. At low to moderate levels of extracellular iodide the synthesis of thyroid hormone is stimulated
. At high levels of extracellular iodide the synthesis of thyroid hormone is inhibited
. Mechanism involves inhibition of H2O generation by iodinated lipid derivative iodohexadecanal

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12
Q

Thyroid hormone storage

A

. Stores a large amt of hormone that slowly turns over
. T3 and 4 remain attached to thyroglobulin in colloid until secretion bc iodide cannot be stored as free anion
. Per molecule thyroglobulin: 7 MIT, 6 DIT, 2 T4, and 0.2 T3
. Once thyroglobulin is iodinated, it is stored in follicles lumen as colloid

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13
Q

Secretion of thyroid hormone

A

. Membrane- bound protein receptor megalin mediates thyroglobulin uptake through endocytosis
. Expression of megalin and its insertion in apical face of follicular cells is TSH-dependent
. Thyroglobulin-containing colloid droplet is moved towards the basal membrane of follicular cell by microtubules and micofilaments
. At same time lysosomes migrate to fuse w/ colloid droplets and T4 and 3 are released to diffuse out of cell into capillary
. Iodide is removed from MIT and DIT and 50% is recycled while rest leaks back into ECF

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14
Q

T/F thyroglobulin is not secreted from gland

A

T

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15
Q

T3 synthesis outside of thyroid gland

A

. 80% from de-iodination of T4 mostly in liver
. 5’-deiodinase (D1 or D2) removes iodine from 5’ position on outer ring of T4 to produce T3
.

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16
Q

Is there any T4 formed outside of thyroid gland?

A

No

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17
Q

How many times more potent is T3 over T4?

A

10 times more potent

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18
Q

Types of 5’-deiodinase

A

D1: liver, kidneys, and thyroid
. D2: CNS and placenta
. D3: peripheral tissues

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19
Q

Reverse T3

A

. 5’-deiodinase can remove iodine from 5 position of inner ring to produce this
. Has no biological effect

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20
Q

Activity of Type I 5’-deiodinase can be dec. ___

A 
. Burns 
. Trauma
. Advanced cancer
. Renal failure
. MI
. Febrile states
. Starvation 
. Administration of high glucocorticoids
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21
Q

Pathological conditions that dec. T3 production continued effect

A

. Dec. T3 production

. Since 5’-deiodinase catalyze the metabolism of rT3 to T2 the rT3 are consequently inc.

22
Q

TSH reaction to plasma T3 decrease during pathological conditions that dec. type I 5’-deiodinase

A

. No compensatory rise
. Type II 5’-deiodinase mediates the conversion of T4 to T3 w/in pituitary and CNS and is NOT affected by pathological conditions
. Local T3 in pituitary remains normal so thyrotrophs see adequate amounts of T3

23
Q

Thyroid transport

A

. Most T3 and 4 is attached to proteins produced by liver

. Small amt exists in plasma as free, unbound hormone

24
Q

Binding proteins for T4

A

. Thyroxine-binding globulin (TBG, 70%)
. Albumin (10%)
. Thyroxine-binding pre-albumin (TBPA, 20%)

25
Q

Things that cause inc. TBG

A

. Pregnancy
. Newborn state
. Oral contraceptives and other estrogen sources
. Infectious and chronic active hepatitis
. Genetically determined

26
Q

Things that dec. TBG

A 
. Androgens and anabolic steroids 
. Large dose of glucocorticoids 
. Chronic liver disease 
. Severe systemic illness
. Active acromegaly 
. Kidney disease w/ proteinuria
. Genetically determined
27
Q

T3 binding proteins

A

. TBG 70%

. Albumin 40%

28
Q

Assessment of thyroid function must consider 2 things:

A

Degree of protein binding

. Measurement of bound and free hormone in plasma

29
Q

Half life for T3, T4, and rT3

A

. T3: 1 day
. T4: 6 days
.rT3: 0.7 days

30
Q

General functions of thyroid hormones

A

. Adjusts O2 consumption
. ATP synthesis
. Heat production
. Adjusts these based on heat production, alterations in energy requirements, supply of calories, and temperature of environment

31
Q

Places thyroid hormone acts on in cell

A

. Mitochondria: enhance conversion of substrates into metabolic energy
. Plasma membrane: inc. entry of substrates into cell
. Nucleus: induce protein synthesis (mitochondrial respiratory enzymes and metabolic enzymes)

32
Q

Thermogenic effect of thyroid hormones

A

. Heat production by inc. metabolism and O2 consumption
. Effect occurs in tissues EXCEPT brain, ant. Pituitary, gonads, and spleen
. Develops after latency period of several hrs to days
. Stimulates Na/K-ATPase that generates ADP to stimulate mitochondrial O2 consumption and heat production
. Stimulate futile cycles of catabolism and anabolism to create heat
. May induce expression fo mitochondrial uncoupling proteins (thermogenin)
. Protein dissociates oxidative phosphorylation from ATP generation so mitochondria produces heat w/o generating ATP

33
Q

Metabolic effects of thyroid hormones

A

. Alters metabolism of carbs, far,and protein
. Permissive to metabolism, E, GH, and insulin
. Metabolism of substrate supports prevailing O2 consumption and requirements for heat production

34
Q

Cardiovascular effects of thyroid hormone

A

. Modulates adrenergic activity of heart by variety of mechanisms
. Rate of transcription for alpha-myosin, Ca-ATPase, beta-adrenergic receptors, G-proteins and adenylyl cyclase
. Net effect: inc. HR, SV, and CO
. Blood flow and O2 delivery to tissues is inc.
. Excessive thyroid hormone can be treated by beta-blockers (propranolol)

35
Q

Respiration effects of thyroid hormone

A

. Augments O2 supply and CO2 removal by inc. the rate of ventilation
. Thyroid hormone inc. O2 carrying capacity of blood by enhancing RBC production

36
Q

Effects of thyroid hormone on brain

A

. Does not alter metabolic rate

. Essential for normal system development

37
Q

Effect of thyroid hormone on growth

A

. Permissive for growth hormone to exert its biological effect on target tissues
. Absence of hormone slows growth and development
. Permissive for metabolic effects of hormones that modulate metabolism: E, GH, and insulin

38
Q

Metabolism of thyroid hormones

A

. Metabolized via de-iodination
. None of the di-iodothyronines or mono-iodothyronines have biological effects
. Remaining unmetabolized thyroid hormones are excreted through feces

39
Q

Hypothalamic factors that modulate the release of thyroid hormones

A

. TSH from pituitary

. TRH and somatostatin from hypothalamus

40
Q

Most important physiological regulator of thyroid hormone secretion

A

TSH

41
Q

TSH

A

. Belongs to glycoprotein family
. Synthesized by cells in ant. Pituitary
. Enhances all steps in thyroid hormone production in gland
. Modulates the growth of thyroid tissue itself (trophic effect)

42
Q

Thyroid hormone negative feedback loop

A

. T3 and T4 inhibit release of TRH and TSH from hypothalamus and ant. Pituitary
. Dec. in TSH diminished thyroid hormone secretion
. T3 acts on ant. Pituitary to inhibit TRH receptor synthesis and reduce receptor sensitivity

43
Q

Thyroid hormone levels w/ primary hypersecretion of thyroid hormones by thyroid gland

A

. Inc. T3 and 4

. Dec. TRH and TSH

44
Q

Thyroid hormone levels w/ primary hypersecretion of TSH

A

. Inc. TSH, T3 and 4

. Dec. TRH

45
Q

Thyroid hormone levels w/ inability of thyroid gland to synthesize hormones

A

. Dec. T3 and 4

. Inc. TRH and TSH

46
Q

Thyroid hormone levels w/ insufficient secretion of TSH by ant. Pituitary

A

. Dec. TSH, T3 and 4

. Inc. TRH

47
Q

Estrogen relationship to thyroid hormones

A

. Estrogens inc. thyroxine binding globulin conc. In plasma and elevate total serum conc. Of T4 and T3
. Inc. responsiveness of thyrotroph in ant. Pituitary to TRH possibly through inc. in TRH receptors

48
Q

Age effect on thyroid

A

. Modify thyroid hormones

. T3 serum levels start to decline at middle age while T4 remains constant

49
Q

Effect of glucocorticoids on thyroid hormones

A

. Depress pituitary TSH secretion

50
Q

Nutritional effects of thyroid hormone

A

. Starvation or high glucocorticoids dec. T3 generation from T4 and inc. the accumulation of rT3
. Carb lack appears to play a role in these effects since they can be reversed by administration of carbs

51
Q

Acute Iodine deficiency

A

. Plasma levels of T4 fall, plasma levels of TSH rise
. Initially plasma levels of T3 maintained in normal range (T3 will decline if iodine deficiency is prolonged
. Inc. in TSH combined w/ iodine deficiency inc. the ratio of MIT to DIT that is formed on thyroglobulin
. Ratio of T3 to T4 that is formed on thyroglobulin also inc.
. Majority of T3 comes from thyroid gland rather than de-iodination of T4

52
Q

Chronic iodine deficiency

A

. Inc. levels TSH induce hypertrophy of thyroid cells

. Can lead to goiter

Physio (62 decks)

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