Week 4 Physiology - Endocrine

Question 1

What is the general cellular structure of the thyroid gland, and how does this relate to function?

Answer 1

Gland is composed of multiple exocrine glands, involving follicular epithelial cells surrounding a large pool of colloid.

Thyroid hormone is stored in these large pools of colloid until ready for secretion, and are formed within the follicular cells.

Question 2

What is the arterial supply of the thyroid gland?

Answer 2

Superior thyroid artery, (which is first branch of external carotid) and inferior thyroid artery (branch of subclavian)

Question 3

Describe H-P-T axis?

Answer 3

Hypothalamus secretes TrH, travels via capillary network (hypophyseal portal system) to act on anterior pituitary to secrete TSH, which then acts upon thyroid gland to secrete thyroid hormone

Question 4

What cells to ‘C’ cells of the thyroid gland synthesise?

Answer 4

Calcitonin - for tonin’ the calcium down

Question 5

How is iodine incorporated into TH synthesis?

Answer 5

Iodine trapping which occurs in thyroid gland - transported from blood by Na+/Iodine symporter on basolateral membrane of follicular cell.

Then crosses apical membrane to colloid via Iodine/Cl- exchanger (Pendrin).

Question 6

What is the role of thyroglobulin in thyroid hormone synthesis?

Answer 6

Thyroglobulin is peptide which contains tyrosyl groups that attach iodine. Either MIT or DIT attach to this residue, which determines whether T3 or T4.

Within colloid, it serves as a storage centre for the bound thyroid hormone until signalled for secretion into blood

Question 7

How does thyroid hormone get from colloid to blood?

Answer 7

Iodinated thyroglobulin is re-absorbed into follicular cell via endocytosis, and then intracellularly fuses with lysosomes to hydrolyse the thyroblobin and leave behind the T3 or T4 molecules.

Question 8

Which is more active, T3 or T4?
Which is more abundantly released?

Answer 8

T3 = more active
T4 = more abundant

Question 9

What is the t1/2 of T3 vs T4?

Answer 9

T3 = 24 hours
T4 = 8 days

Question 10

What is the purpose of T4 if it is poorly active?

Answer 10

Large reservoir in circulation that can be peripherally converted to T3

Question 11

Where does the biggest amount of peripheral conversion of T4 occur?

Answer 11

Liver and kidneys

Question 12

What type of receptor is a TrH receptor on anterior pituitary?

Answer 12

GPCR, phospholipase C pathway

Question 13

What type of receptors is Thyrotropin Receptor on follicular cells?

Answer 13

GPCR, GPCR adenylyl cyclase pathway

Question 14

What events occur on binding of TR?

Answer 14

All stages of thyroid hormone synthesis and release

i.e. iodine uptake, iodination of thyroglobulin, endocytosis of thyroglobulin, secretion of TH

Also hyperplasia of thyroid gland if high ongoing activation (goitre)

Question 15

Where is the thyroid hormone receptors usually located?

Answer 15

Almost every cell in body, and within nucleus - for transcription/gene regulation.

Question 16

What physiological effects does thyroid hormone have in the body?

Answer 16

• Increased BMR
• Increased carbohydrate metabolism + futile anabolism and catabolism to increase metabolic rate
• Increased beta-adrenergic receptor expression, increased sensitivity to catecholamines

Question 17

What are clinical features of hyperthyroidism?

Answer 17

Heat intolerance
Proximal myopathy
Weight loss
Diarrhoea
Tremor
Tachycardia
Hyperreflexia

Question 18

What are the clinical features of hypothyroidism?

Answer 18

Fatigue
Weight gain
Bradycardia
Constipation
Mental slowing
Depression
Alopecia

Question 19

What are the layers of the adrenal cortex and corresponding hormones?

Answer 19

Cortex:
- Zona glomerulosa = mineralcorticoid
- Zona fasiculata = glucocortoid
- Zona reticularis = sex hormones

Medulla
- Dopamine
- Noradrenaline
- Adrenaline

Question 20

What are the 2 effects of aldosterone at the collecting duct of kidney?

Answer 20

1. Increased ENAC insertion (fast effect) - causing increased sodium reabsorption
2. Increased Na+ reabsorption via Na+/K+ exchanger, loss of hydrogen ions

Question 21

What leads to increased secretion of aldosterone?

Answer 21

Low pressure/volume states
Increased renin secretion

Question 22

What is the trophic hormone for cortisol?

Answer 22

CrH from hypothalamus, then ACTH from anterior pituitary

Question 23

When is peak production/secretion of cortisol?

Answer 23

Between 4am-10am

Question 24

What are the permissive effects of glucocorticoids?

Answer 24

Increased effects of catecholamines/pressor reactivity

Decreased bronchial reactivity

Question 25

What effect do glucocorticoids have on metabolism?

Answer 25

Increased protein catabolism
Increased glycogenolysis and gluconeogenesis
Increased BSL
Antagonism of insulin effects peripherally
Increased lipolysis

Question 26

Where are the parathyroid glands located?

Answer 26

4 glands, posterior aspect of thyroid gland

Question 27

What causes release of PTH?

Answer 27

Lowered Calcium levels in plasma

Question 28

What are the mechanisms by which PTH increases plasma levels of calcium?

Answer 28

1. Activation of osteoclasts –> release of Ca2+ and PO4-
2. Increased Ca2+ reabsorption in kidneys via paracellular route in PCT and under PTH regulated Ca2+ channels in DCT
3. Increased intestinal absorption of Ca2+ indirectly via stimulating kidneys to transform Vit D to active form, which acts at enterocytes to increase absorption of calcium
4. Reduced PO4 reabsorption in kidneys, meaning less PO4 will complex the ionised calcium and blood and render it unavailable for cellular processes