Thyroid Gland Flashcards
Describe the location of the thyroid gland
- Below thyroid cartilage (Adams apple), just above supersternal notch
- Lies against and around front larynx and trachea
Explain the appearance of thyroid gland
- Butterfly shape with 2 lobes joined by isthmus
- Isthmus extends from 2nd and 3rd rings of the trachea
Describe the structure of the thyroid gland
- Follicular cells arranged in spheres called thyroid follicles which are separated by connective tissue
- Follicles filled with colloid, a deposit of thyroglobulin
- Colloid is extracellular even through it is inside the follicle
- Parafollicular cells produce calcitonin (calcium homeostasis) and found in connective tissue
How is radiography on the thyroid performed
- Radiography done through thyroid uptake and scan or MRI
- Technetium-99 (sometimes iodine) taken orally and used for isotope scanning
What are the hormones produced in the thyroid gland
- Follicular cells produce thyroxine and T3
- Parafollicular cells produce calcitonin
Explain the process of T3&T4 synthesis in follicular cells
- Iodide enters through iodide trap against concentration gradient
- Amino acids synthesise thyroglobulin on basal surface of epithelium
- Thyroglobulin undergoes exocytosis and secreted into lumen of follicle
- Oxidation of iodide produce iodinating species
- Iodination of side chains of tyrosine residues in thyroglobulin form MIT (mono-iodotyrosine) and DIT (di-iodotyrosine)
- Coupling of DIT with MIT or DIT to form T3 & T4 respectively within thyroglobulin
- Thyroxine or T3 reuptake through pinocytosis and proteolytic cleavage of thyroglobulin occurs to release T3 & T4 into plasma
How are T3 and T4 stored
Stored extracellularly in lumen of follicles as part of thyroglobulin molecules (before pinocytosis)
What is the role of thyroid peroxidase
- Thyroid peroxidase - regulates 3 iodine reactions
- Oxidation of iodide to iodine (requires presence of hydrogen peroxide)
- Addition of iodine to tyrosine acceptor residues on the protein thyroglobulin
- Coupling of MIT and DIT to generate thyroid hormones within the thyroglobulin protein
Is T3 or T4 secreted more
- Most T4 is converted to T3 outside thyroid (mostly in liver and kidney)
- 90% of thyroid hormone secreted is T4
- Biological activity of T3 is 4 times that of T4
How is thyroid hormone secretion controlled
- Hypothalamus releases thyrotropin releasing hormone (TRH) which stimulates anterior pituitary to produce thyroid stimulating hormone (TSH)
- Thyroid hormones effect virtually every cell in the body by effecting cellular differentiation and development or effect metabolic pathways
- The entire pathway is controlled through negative feedback
- Depends on circulating volume of T3 and T4, stress (increases release), temperature (fall in temp increases release)
Explain the structure and role of TSH
- Glycoprotein hormone consisting of alpha and beta subunit covalently bound
- Alpha subunit also present in FSH and LH, but beta subunit provides unique biological activity
- G protein receptor activation by TSH resulting in iodide uptake and oxidation
- Results in thyroid hormone synthesis and release
- TSH induces second messenger pathways
- Results in thyroid hormone synthesis and release
How are thyroid hormones transported in the blood
- Lipid soluble hormones - need protein to transport in blood
- Thyroxine binding globulin, pre-albumin and albumin transport thyroid hormone
What happens to T3 and T4 plasma levels in response to oestrogen
- Oestrogens increase synthesis of thyroxine binding globulin during pregnancy - produces fall in free T3 and T4 in circulation as more is bound
- Removes inhibitory feedback - more TRH and TSH produced
- Free T3 and T4 returns to normal but total amount in blood increased
- Removes inhibitory feedback - more TRH and TSH produced
Explain the effects thyroid hormones have on the body
- Increase in basal metabolic rate and heat production
- In most tissues (except testes, brain and spleen)
- Increase size and number of mitochondria
- Stimulating synthesis of enzymes in respiratory chain
- Stimulation of metabolic pathways
- Lipid metabolism - stimulates lipolysis and ß-oxidation of fatty acids
- Carbohydrate metabolism - stimulate uptake of glucose in cells, gluconeogenesis and glycogenolysis
- Important in normal growth and development
- Affect bone mineralisation - physical growth
- Synthesis of heart muscle protein
- Sympathomimetic effects
- Promote effects of sympathetic nervous system
- Increase target cell receptors of adrenaline and noradrenaline
- Tissue specific effects
- Cardiovascular system - increase heart’s responsiveness to adrenaline
- Increase cardiac output and peripheral vasodilation to carry extra head to body surface
- Nervous system - essential for both development and adult function
- Increase myelination of nerves and development of neurons
- Mental retardation due to lack of development of nervous system
- Increase myelination of nerves and development of neurons
- Cardiovascular system - increase heart’s responsiveness to adrenaline
Explain the mechanism of action of T3 and T4
- T3 and T4 cross plasma membrane and interact with specific receptors in nucleus and mitochondria
- Nuclear receptors
- 10 fold greater affinity for T3 than T4
- Function as hormone-activated transcription factors
- When thyroid hormone binds, complex promotes gene expression rather than repress (when DNA bound)
- New protein facilitate net effects of hormone