L08 - Physiology of thyroid Flashcards by Max Kam

Which muscles cover the thyroid gland?

Sternohyoid and Sternothyroid

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Anatomical location of the thyroid gland?

C5-T1

Below cricoid cartilage and 2nd to 4th trachea rings

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Define the function of cell types in thyroid gland?

Follicle cavities contain colloid

Principal/ follicular cells secrete thyroid hormones T3,T4

Parafollicular cells secrete calcitonin = regulation of calcium metabolism

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Explain the mechanism of Calcitonin release upon sensing high calcium levels?

1) Calcium sensing receptor (CaSR) = GPCR: sense rising Ca on parafollicular cells
2) G proteins trigger activation of PLC
3) Produce DAG, IP3&raquo_space; IP3 increase Ca2+ levels&raquo_space; exocytosis of calcitonin

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Which organs respond to calcitonin? What is the receptor?

Kidney = more excretion
Bone = less resorption 
intestines = less absorption

> > overall lower plasma Ca

express high-affinity calcitonin receptor (GPCR)

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Effect of calcitonin on bone?

Osteoclasts calcitonin receptor activated
»cAMP/ PKA pathway
» Inhibit osteoclast motility
» retraction of osteoclasts and inhibit bone resorption
» less Ca released into blood

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Effect of calcitonin on kidneys and GIT?

1) Inhibit Ca reabsorption in tubules, increase Ca excretion by urine
2) Produce less CALCITRIOL&raquo_space;Decrease GI absorption of Ca

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Origin and action of thyrotropin-releasing hormone (TRH)?

Origin = Parvocellular neurons of paraventricular nucleus (PVN) from hypothalamus

Action = Binds to its receptor (Gαq protein-coupled) in thyrotrophs in anterior pituitary = release thyroid stimulating hormone (TSH)

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Origin and action of TSH?

Origin = thyrotrophs in anterior pituitary

Action = bind TSH receptor (GPCR) on basolateral membrane of thyroid follicular epithelial (principal) cells&raquo_space; synthesis and secretion/release of thyroid hormones

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Intracellular reactions at the thyroid follicular cells after TSH stimulation?

cAMP and PLC pathway activaton:

cAMP:

Expression of Na/I symporter at basolateral membrane
Translocate Pendrin to apical membrane
Production of thyroid peroxidase
Produce and secrete thyroglobulin into colloid

PLC:
- Generate H2O2 by dual oxidase

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What drives the intake of Iodide into principal follicular cells at basolateral membrane?

Uptake by NIS: co-transport 2Na+ and 1I-

Na+ gradient is the driving force

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How is iodide transported across the principal cells of thyroid?

1) Uptake by NIS

2) Efflux into follicular lumen by Pendrin

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Role of thyroid peroxidase? ***

1) Oxidize iodide via H2O2 generated by dual oxidase
2) Incorporate Iodide into selected tyrosyl residues of THYROGLOBULIN&raquo_space; form mono-iodotyrosine(MIT) or di-iodotyrosine(DIT)

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Molecular composition of T4 and T3?

T4 = 2 DIT - 1 adenine

T3 = MIT + DIT - 1 adenine

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Where is iodinated thyroglobulin stored?

In follicle cavity as colloid

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Iodinated thyroglobulin can be released from the follicle cavities without modification T or F?

False

T3 and T4 need to be liberated from thyroglobulin scaffold before release

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Describe the liberation of T3 and T4 into blood stream?

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1) Endocytosis of iodinated thyroglobulin from follicle lumen at apical membrane
2) digestion by lysosomes to liberate T3, T4 from scaffold, thyroglobulin recycled back to follicle lumen
3) secreted as free hormone into blood at basal membrane

Compare the amount of T4 and T3 secreted by thyroid?

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plasma concentrations of T4 = 40-fold higher than those of T3

Describe how T3, T4 is carried in blood?

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Insoluble, need carrier proteins:

70%: thyroxine-binding globulin
~15%: albumin
~10%: transthyretin
~5% (more in liver disease): unbound T4 (active in circulation)

Half-life of T3 and T4?

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T4: 7 days

T3: 1 day

Describe the processing of thyroid hormone at target cells?

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T4 = prohormone
T3 = active
T4 must be converted to T3 by DEIODINASE I or II

> > T3 bind to thyroid hormone receptor(THR)
activate thyroid hormone-response element (TRE)
transcriptional regulation of target genes

Define the 2 types of thyroid hormone receptors?

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THRα, THRβ

Extent of expression of THRα, THRβ ?

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Expressed in all tissues

THRα: mainly in brain, peripheral tissue (heart, skeletal muscle, kidney, liver)

THRβ: highly in brain, head region (pituitary gland, retina, inner ear, lung etc.)

3 principle functions of thyroid hormones?

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 Growth, development

 Control of body temperature

 Control of basal metabolic processes

Define the effect of thyroid hormone on nervous system?

1) Regulate neuronal migration, myelination >> fetal, post-natal CNS development 2) Enhance sympathetic nervous system activity >> wakefulness, alertness

Define the effect of thyroid hormone on CVS?

1) VASODILATION to decrease systemic vascular resistance 2) Increase cardiac output: Regulate genes important for myocardial contraction, electrochemical signaling e.g. β1-adrenergic receptors, SERCA (Ca2+ reserve)

Effects of thyroid hormone on skeletal muscles?

 Development of muscle mass  Differentiation of contractile characteristics

Effect of thyroid hormone on Gut?

Increase glucose absorption , rate of secretion of digestive enzymes, motility of GI tract

Effect of thyroid hormone on Adipose tissue?

- Promote thermogenesis: weight loss in brown adipose tissue - Increase β-adrenoceptor expression = catecholamine-mediated lipolysis

Effect of thyroid hormone on skin?

Regulate epidermal cell proliferation, homeostasis

Explain how hyperthyroidism occurs in pregnancy?

hCG shares same α subunit (structurally similar) as LH, FSH, TSH >> acts as weak agonist of TSH receptor (without increase in TSH level) >> turn on thyroid function

Pathogenesis of Grave's disease?

autoimmune: thyroid-stimulating immunoglobulin (TSI) directly stimulates TSH receptor >> continuously stimulates thyroid hormones (T3, T4) production without TSH increase

List symptoms of hyperthyroidism?

- Intolerance to heat; facial flushing; weight loss - Graves’s ophthalmopathy: bulging eyes - Goiter (affecting airway, esophagus) - Cardiac hypertrophy/ arrhythmia - Diarrhea - Tremors - Thyrotoxic periodic paralysis

Explain why hyperthyroidism causes tremor?

thyroid hormone inhibits acetylcholinesterase >> increase Ach at snaptic celeft >> tremors, muscle fatigue, degeneration

Explain how hyperthyroidism cause Thyrotoxic periodic paralysis?

hypokalemia secondary to hyperthyroidism >> increase K+ efflux cause more negative membrane potential >> muscle weakness (e.g. heart, respiratory muscle)

List 4 causes of Hypothyroidism?

1) Autoimmune inflammatory reaction e.g. Hashimoto's thyroiditis 2) Congenital diseases e.g. cretinism: poor development 3) Iatrogenic: removal, irradiation 4) Iodine deficiency

List symptoms of hypothyroidism?

- Intolerance to cold; subnormal temperature; weight gain - Extreme fatigue, muscle weakness - Deep cocky voice - Slow HR - Dry skin with brittle and thick nails and Myxedema - Constipation

Explain why hypothyroidism causes deep cocky voice?

1. Mucopolysaccharide deposits on vocal cord = change vibration frequency 2. Enlargement of thyroid gland = compress laryngeal nerve

Cause of resistance to thyroid hormone?

mutation in the THR = | reduction/lack of end organ responsiveness to TH

Effects of THRα mutation? Symptoms?

hypothyroidism in peripheral tissues: - Nervous system: Impaired neural development + Abnormal cortical layering and cerebellum development (same as THR-B) - Heart: SLOW heart rate (diff. to THR-B) - Intestine: chronic constipation - Bone: delayed development

Compare the T3, T4 and TSH levels between 2 types of THR mutation?

THRα = normal level of T3, T4, TSH THRβ = elevated T3, T4, TSH

Effects of THRβ mutation?

Nervous system: (same as THRa mutation)  Impaired neural development  Abnormal cortical layering and cerebellum development Thyroid: goiter Heart: fast heart rate HPT axis: impaired negative feedback

L08 - Physiology of thyroid Flashcards

(42 cards)