Flashcards in Metabolism - The Thyroid Deck (27)
Where is the thyroid gland?
Anterior to the lower larynx and trachea. The 2 lobes wrap around the cricoid cartilage and are held by an isthmus.
What is the blood supply to the thyroid gland?
Inferior and superior thyroid arteries.
Inferior, middle and inferior thyroid veins.
How is T3/4 formed?
1). An active transport pump pumps Na+ out of the follicular cells and K+ in
= conc gradient so Na+ can move back into cells via Na+ /I- symptorter, therefore bringing Iodide into the cell.
2). The I- is concentrated using an iodide trap.
3). I- is secreted into the colloid, where peroxidase aids it in reacting with the tyrosine residues present on the thyroglobulin of the colloid.
--> if one iodine binds to tyrosine, it is MIT
--> if 2 iodine molecules bind to tyrosine, it is DIT
4). A vesicle forms in the colloid in which DIT/MIT are packaged.
5). The DIT can react with another DIT or with MIT to give T4 or T3 respectively.
6). Vesicle is taken in via endocytosis.
How is TSH synthesised and where is it secreted from?
It is synthesised and in the RER and glycosylated on its cisternae, before being packaged and sent to the Golgi.
What is the structure of TSH?
A large glycoprotein of alpha and beta unit.
Where is TSH secreted and what controls this?
The anterior pituitary
Why is T4 usually made n greater amounts?
It is more stable (as it has a greater affinity for TBG than T3 so is less likely to be free and therefore used) and can be converted into the less stable form T3 for usage by deiodination.
How does deiodination occur and where?
Removal of the 5' iodine in the liver or kidney.
Removing the 3' creates inactive T3
How do T3/4 cause their effects on cells?
1). They enter the cell and act upon high affinity receptors located in the nucleus.
2). Binding = a conformational change which unmasks the DNA binding domain,
3). The THreceptor complex can now bind to this domain, and activate or inhibits transcription of certain genes.
What are the non tissue specific effects of T3/4?
-Increases BMR (more O2 consumption, more mitochondria etc)
-Stimulation of catabolic pathways
-Increase tissue responsiveness to the SNS, and some hormones
-Promotes growth and development of tissues (protein synthesis)
What are the tissue specific effects of T3/4?
- increased myelination
- increased mental activity and reflex speed
- increased cardiac output
- increases protein turnover
What can effect T3/4 levels other than level of TSH/TRH?
What is TBG and what increases its synthesis?
It is the protein which carries T3/4 in the blood, and oestrogen increases its synthesis.
What are is the primary causes of hypothyroidism?
- autoimmune destruction of the follicular cells in the thyroid gland or production of an antibody which blocks the TSH receptors.
What are the symptoms of hypothyroidism?
Mild weight gain (slowing of catabolism)
Myexderma (swelling of skin due to oedema because of increased
GAG deposition, less protein turnover)
Bradycardia (decreased HR)
Cold intolerance (already generating little heat)
Mood swings, poor concentration/memory/initiative
What is the treatment for hypothyroidism and how must this be dealt with?
- doseage must be given and corrected in a trial/error method in order to avoid hyperthyroidism
- when there are no longer any signs of hypo/hyperthyroidism, measure the blood TSH conc. If this is normal and T4 is normal, the pituitary gland is functioning normally.
What effect does hypothyroidism have if it occurs untreated at birth?
Congenital neonatal hypothyroidism.
What is euthyroidism?
When the thyroid is functioning normally.
What is compensated euthyroidism and what is done about it?
When TSH is high but T3/4 are still normal.
The patient simply has regular check ups.
What is sick euthyroidism and what do we do about it?
Sick inpatients may have abnormal T3/4 levels, however, this is actually due to stress as they're ill.
We don't measure the T3/4 of ill inpatients unless there is a very strong suspicion of thyroid problems.
What are the causes of hyperthyroidism?
1). Graves' disease
- production of an antibody which stimulates TSH receptors on the follicular cells (female preponderance)
2). Excessive iodine intake or T3/4 therapy
3). An adenoma secreting TSH or T3/4
- pituitary or ectopic
What is the treatment for hyperthyroidism?
1). Carbimazole - prevents iodine uptake into colloid = no T3/4
2). Radioactive iodine treatment - taken up into cells and therefore destroys them
3). Surgery - removal of the thyroid gland BUT this can cause hypothyroidism
What are the symptoms of hyperthyroidism?
1). Mild weight loss - increase in catabolism = uses fats
2). Tachycardia - increased HR
3). Exophthalmos - bulging eyes and eyelid lag
4). Heat intolerance - already producing a lot
5). Hyper reflexive - due to increase in reflex speed and myelination of neurones
7). Increased bowel movements
How does a goitre occur and what is it showing?
Can occur in hypo/hyperthyroidism.
In hyperthyroidism, it is due to increased TH levels causing the growth and division of follicular cells.
What does TSH stimulate?
1). Growth and division of follicular cells
2). Synthesis of thyroglobulin
3). Coupling reactions of MIT/DIT
4). Iodide trap
5). Exocytosis of T3/4
What is a quaternary cause of hypothyroidism?
- failure to iodinate tyrosine residues