Adrenal gland Flashcards
how many carbons are in cholesterol and describe the structure
26
see google docs
What does the adrenal cortex secrete
Corticosteriods
Name 3 types of corticosteroids
Mineralocorticoids ( aldosterone) Glucocorticoids ( cortisol) Sex steroids( androgens, oestrogens)
what is a steroid
Hormone that is made from cholestrol
What is the precursor material for steroid hormones
Cholesterol
what is the effect of angiotensin II on the adrenals
Activation of : 1) 3 Hydroxysteroid dehydrogenase 2) 21hydroxylase 3) 11 hydroxylase 4) 18 hydroxylase by side chain cleavage
what is the precursor molecules for aldosterone
cholesterol
What does aldosterone do
Control blood pressure , sodium and lowers potassium
retains water and sodium in kidney and increase K excretion
what is the effect of ACTH on the adrenals
Activation of following enzymes by side chain cleavage:
1) 3 hydroxysteroid dehydrogenase
2) 21 hydroxylase
3) 11 hydroxylase
4) 17 hydroxylase
How does cholesterol turn to aldosterone
Cholesterol –> progesterone –> 21 hydroxylase ( enzyme) –> 11-deoxycorticosterone
–> 11 hydroxylase ( enzyme) –> corticosterone –> 18hyroxylase ( enzyme) –> aldosterone
How does cholesterol turn into cortisol
1) Cholestenone 2) Progesterone ( 17 hydroxylase) 3) 17-OH progesterone 21 hydroxylase 4) 11-deoxycortisol 11 hydroxylase
How does cholesterol turn into sex steroids
1) cholesterol
2) progesterone
17 hydroxylase
3) Sex steroids
4) Androgens
5) Oestrogens
How does cortisol fluctuate throughout the day
Diurnal rhythm
Highest after waking and lowest at night
What is 1ary adrenal failure and what is the common cause?
disease that destroys the adrenal cortex
causes:
1) autoimmune ( common in uk) ( antibodies attack adrenal cortex)
2) TB of adrenal glands ( worldwide)
3) Congenital adrenal hyperplasia
Symptoms of adrenocortical failure ( ie Addison’s)
Fall in blood pressure
Loss of salt in the urine
Increased plasma potassium
( first 3 due to lack of cortisol)
Fall in glucose due to glucocorticoid deficiency
High ACTH resulting in pigmentation
High ACTH due to loss of negative feedback by cortisol on the pituitary.
POMC → ACTH + MSH (leading to hyperpigmentation).
Also breaks down into endorphins, enkephalins and other peptides.
Vitiligo
Muscular weakness
Eventual death due to severe hypotension : Addisonian crisis
Why do you get hyperpigmentation / tanned in Addison’s disease
Loss of negative feedback of cortisol to pituitary –> lead to high levels of ACTH
to make ATCH
POMC –> ACTH + MSH ( MSH leads to hyperpigmentation)
Note : could also be due to autoimmune vitiligo ( which may coexist)
Why do pateints with Addison’s have low bp?
No cortisol / aldosterone so bp low
Causes of adrenocortical failure
Adrenal glands destroyed
or enzymes in steroid synthetic pathway not working ( common)
What tests do you do for Addions
1) 9 am cortisol ( low in Addison’s)
2) look out for ACTH ( high in Addison’s)
3) Short synACTHen test where you give 250ug of synACTHen IM ( intramuscular) to measure cortisol response if after a while cortisol levels don’t increase = Addison’s
What does a typical Addison’s pateints results
A typical Addison’s patient:
cortisol at 9am of 100 (normal range = 270-900)
cortisol of 150 after administration of synacthen measured at 9:30am (normal range = >600)
What are treatment of Adrenal failure
1) Fludrocortisone ( 50 - 100mg daily)
2) 1-2 dehydro - hydrocortisone aka prednisolone ( 4-4mg once daily)
3) Oral hydrocortisone ( 3x daily would prefer prednisolone instead)
Why use fludrocortisone not aldosterone
Fludrocortisone is aldosterone with a H replaced by a F.
Normal half life of aldosterone is too short for safe once daily administration. As fluorine does not exist in natural steroid its presence reduces metabolism. It binds both to Mineralocorticoid receptor and Glucocorticoid receptors and has a half life of 3.5 h and effects can be seen for 18h
Why cant use used oral hydrocortisone as a treatment of adrenal failure
too short half life for once daily administration .
If taken more more than OD it creates peaks and troughs which are v harmful
why use prednisolone instead of oral hydrocortisone
Prednisolone has longer half life + is more potent (higher binding affinity)
