ENI - The thyroid gland Flashcards
What is the embryological origin of the thyroid gland?
- Downgrowth from pharyngeal endoderm of developing tongue (follicular cells)
- C cells are from ultimobranchial body
Describe the structure of the thyroid glands
- Thyroid follicles
- Single layer of follicular cells around lumen filled with protein rich colloid where hormones are stored
- Microvilli on colloid side
- Cell cells large, pink cytoplasm, interspersed between follicular cells
- Lots of contact with capillaries on basal side
- Tight junctions between neighboruing cells
What is the function of the parafollicular cells?
- Connective tissue near follicles
- secrete calcitonin
What is the colloid?
- Stored within follicles
- Primarily thyroglobulin
- T3 and T4 bound to thyroglobulin
- Normally only 10% of tyrosines in thryroglobulin are iodinated
What is the function of iodine in the body?
Thyroid hormone synthesis, this is its only role
Describe the synthesis of the thyroid hormones
- Iodide pumped from blood into follicular cells using secondary active transport with sodium, down sodium concentration gradient (is against iodine gradient)
- Stimulates by TSH
- Once iodide in, diffuses through cell to colloid end
- Thyroperoxidase (TPO) at colloid end
- Golgi in cell produce thyroglobulin (with 120 tyrosine residues), transported into colloid via exocytosis
- Thyroperoxidase catalyses iodination of thyroglobulin using the iodide
- Iodide oxidised to iodine as H2O2 is reduced
- Iodine added to tyrosine within thyroglobulin, catalysed by iodinase enzyme
- This coupling reaction produces monoiodotyrosinase or diiodotyrosinase
How are T3 and T4 produced from monoiodo and diiodotyrosinase?
- Mono and diiodo combine to form T3
- 2x diiodo to form T4
Describe the process of thyroid hormone secretion
- Get from colloid to basal membrane and into capillary network
- Endocytosis for colloid uptake
- Intracellular vesicles fuse with lysosomes
- Lysosomal enzymes split thryoid hormones from thyroglobulin
- Hormones diffuse across basal plasma membrane into interstitium (lipid soluble so bound to thyroid hormone binding globulin or albumin)
Compare the blood concentrations of the thyroid hormones
- 50-60 times higher blood levels of T4 compared to T3 in circulating blood concentrations
- Very small amount of free hormones (0.03% T4, 0.3% T3)
- Equilibrium between bound and free
Describe the deiodination of thyroxine
- Deiodinated to triiodothyronine within cells of many tissues, esp liver and kidneys
- Free hormones enter cells
- Can be converted to T3 or rT3
- Therefore deiodination pathways are mechanism for regulation
- Active T3 using 5’-deiodinase
- rT3 using 5-deiodinase
- Different position of iodine removed
What is the function of rT3?
- No action and so will slow metabolism
- Adaptation to starvation or illness
How are thyroid hormones excreted?
- Catabolised by liver and kidney
- Further deiodinated to diiodotyrosine and monoiodotyrosine
- Produces conjugated excretory products
- Iodide either recycled or excreted via urine
What are the actions of thyroid hormones?
- Development and growth
- Increase metabolic actions
- Increase breakdown of glycogen in MSK system
- Increased efficiency of oxygen delivery to tissues
- Respiratory system effects
- Maintain normal function of adult nervous system
- Reproductive system
- Gastrointestinal system
What are the effects of thyrotropin hormone (TSH)?
- Increased endocytosis and proteolysis of thyroglobulin from colloid
- Increased activity of Na+/I- symport
- Increased iodination of tyrosine
- Increased size and secretory activity of thyroid follicular cels
- Increased number of follicular cells
- Goitre (enlarged from TSH stimulation)
Describe the regulation of TSH and TRH
- Hypothalamus secretes TRH
- Stimulates TSH release from anterior pituitary (water soluble)
- Acts on thyroid gland
- Adenyl cyclase signal transduction pathway
- Negative feedback from thyroid hormones in long and short loops
Where is most T3 produced?
In the tissues, by deiodination of T4
Which of the thyroid hormones is the primary biologically active hormone?
T3
What are the effects of thyroid hormones on development?
- Required in foetal period and first few months
- Lack leads to reduced development and maturation of brain cells (permanent, cretinism in humans)
What are the effects of hypothyroidism on growth?
- Required for normal growth
- In young animal: growth retardation, smaller, shorter bones, dealyed closured of physes
Describe the role of thyroid hormones in carbohydrate metabolism
- Stimulate glucose metabolism
- Increase glucose uptake into cells
- Insulin sensitivity
- Insulin secretion
- Glycolysis in liver and skeletal muscle
- Gluconeogenesis
Describe the role of thyroid hormones in fat metabolism
- Enhances fat metbaolism
- Mobilise lipids fom adipose stores
- Accelerate oxidation of lipids to produce energy (by increasing size and number of mitochondria as this is where beta-oxidation takes place)
Describe the role of thyroid hormones in basal metabolic rate
- Increase BMR in all tissues except brain, gonads nad spleen
- Increase heat production
- Increase oxygen consumption
What is the effect of hyperthyroidism on basal metabolic rate and body weight?
- BMR twice normal level
- Weight loss
What is the effect of hypothyroidism on basal metabolic rate and body weight?
- BMR 50% of normal
- Weight gain
Describe the effect of hypothyroidism on the musculoskeletal system
- Reduced muscle tone, changes in fibre type
- Not seen clinically, very little cahnge in MSK system seen
Describe the effect of hyperthyroidism on the musculoskeletal system
- Protein depletion
- AAs used for gluconeogenesis
- Muscle tremors
What are the normal physiological effects of the thyroid hormones on the cardiovascular system?
- Increased blood flow and cardiac output
- Increased heart rate
- Increased contractility
- Aims to increase oxygen supply to the body
What are the effects of hypothyroidism and hyperthyroidism on the cardiovascular system?
Hypo: bradycardia
Hyper: tachycardia
What is the normal action of the thyroid hormones on the respiratory system?
- Increased basal metabolic rate
- Increased demand for oxygen thus increased excretion of carbon dioxide (increased ventilation)
What are the effect of hypo and hyperthryoidism on respiration rate?
- Hypo: little change seen
- Hyper: increased respiration rate
What is the normal action of the thyroid hormones on the nervous system?
- Development
- Enhances sympathetic nervous system (increases epinephrine receptors)
- Needed for optimal nerve conduction
What is the effect of hypothyroidism on the nervous system?
- Slower reflexes
- Lethargic
- Mentally slower
- Require more sleep
What is the effect of hyperthyroidism on the nervous system?
- Hyperexcitable
- Tired becuase of increased nerovus and muscular activity, but difficulty sleeping
What is the effect of hypothyroidism on the reproductive system
- Reduced sexual drive
- Reduced sperm production
- Irregular or absent cycling