(endo) adrenal gland Flashcards
where are the adrenal glands found?
superior to the kidneys
describe the arterial supply of the adrenal glands
each adrenal gland is supplied by three groups of arteries:
- superior adrenal arteries
- middle adrenal arteries
- inferior adrenal arteries
describe the venous drainage of the adrenal glands
right adrenal gland = directly into the inferior vena cava
left adrenal gland = first, into the left renal vein and then into the inferior vena cava
how does the arterial supply of the adrenal glands compare to their venous drainage?
many arteries supply the adrenal glands but only one vein drains each one
how is the venous drainage of the right adrenal gland different to that of the left?
right = directly into IVC left = left renal vein into IVC
what are the two parts of the adrenal gland?
adrenal cortex (outer) adrenal medulla (middle)
what are the components of the adrenal cortex?
zona glomerulosa
zona fasciculata
zona reticularis
what is the function of the adrenal cortex?
secretes corticosteroids
mineralocorticoids, glucocorticoids, sex steroids
what is the function of the adrenal medulla?
secretes catecholamines
adrenaline, noradrenaline
name the corticosteroids secreted by each zone of the adrenal cortex
1) zona glomerulosa = mineralocorticoids (e.g. aldosterone)
2) zona fasciculata = glucocorticoids (e.g. cortisol)
3) zona reticularis = sex steroids (e.g. androgens, oestrogen)
name the catecholamines secreted by the adrenal medulla
adrenaline/epinephrine (80%)
noradrenaline/norepinephrine (20%)
[dopamine - noradrenaline precursor]
name the primary mineralocorticoid
aldosterone
name the primary glucocorticoid
cortisol
name the primary sex steroids
androgens, oestrogens, progestogens
what type of cells are found in the adrenal cortex?
epithelial cells and their associated capillary networks
what type of cells are found in the adrenal medulla?
neuroendocrine/chromaffin cells
what are chromaffin cells?
neuroendocrine cells found mostly in the medulla of the adrenal glands (i.e. phaeochromocytes)
= cells that receive neuronal input that then triggers the secretion hormones (e.g. adrenaline, noradrenaline) into the bloodstream
why is dopamine found in the adrenal medulla?
dopamine is the precursor molecule to noradrenaline, which is synthesised in the adrenal medulla
what is the primary molecule from which steroid hormones are synthesised?
cholesterol
describe how cholesterol is converted into progesterone
cholesterol TO pregnenolone = side-chain cleavage enzyme
pregnenolone TO progesterone = 3-beta hydroxy steroid dehydrogenase
which enzyme catalyses the conversion of cholesterol to pregnenolone?
side-chain cleavage enzyme
which enzyme catalyses the conversion of pregnenolone to progesterone?
3-beta hydroxy steroid dehydrogenase
which two corticosteroids are normally given rise to from progesterone?
1) aldosterone (mineralocorticoid)
2) cortisol (glucocorticoid)
describe how progesterone is converted into aldosterone
21 hydroxylase (progesterone to 11-deoxycorticosterone)
11 hydroxylase (11-deoxycorticosterone to corticosterone)
18 hydroxylase (corticosterone to aldosterone)
describe how progesterone is converted into cortisol
17 hydroxylase (progesterone to 17 hydroxy-progesterone)
21 hydroxylase (17 hydroxy-progesterone to 11 deoxycortisol)
11 hydroxylase (11 deoxycortisol to cortisol)
list the enzymes required to convert cholesterol into aldosterone
1) side-chain cleavage enzyme
2) 3-beta hydroxysteroid dehydrogenase
3) 21 hydroxylase
4) 11 hydroxylase
5) 18 hydroxylase
list the enzymes required to convert cholesterol into cortisol
1) side-chain cleavage enzyme
2) 3-beta hydroxysteroid dehydrogenase
3) 17 hydroxylase
4) 21 hydroxylase
5) 11 hydroxylase
what is the two main mechanisms of action of aldosterone?
1) stimulates sodium reabsorption from the DCT and the collecting duct (= increasing water reabsorption and raising blood volume)
2) stimulates K+ and H+ ion secretion into the tubular filtrate from the bloodstream
where does aldosterone act?
1) kidney = distal convoluted tubule & cortical collecting duct
2) sweat glands
3) gastric glands & colon
how does aldosterone increase blood volume?
increased sodium reabsorption from the tubular filtrate into the bloodstream via apical ENaCs & basolateral Na+-K+ ATPases
increased sodium reabsorption stimulates more water reabsorption into the bloodstream in order to regulate the osmotic gradient, increasing blood volume
which molecule regulates aldosterone secretion?
renin
how does the renin-angiotensin system regulate aldosterone secretion?
liver releases angiotensinogen
angiotensinogen is converted into angiotensin I via renin
angiotensin I is converted into angiotensin II via ACE (angiotensin-converting enzyme) released in the lungs
angiotensin II acts on the zona glomerulosa of the adrenal gland to increase aldosterone synthesis
from where is renin released?
juxtaglomerular apparatus
when is renin released?
when the arterial blood pressure falls, the decrease is detected by baroreceptors that subsequently increase renin secretion from the juxtaglomerular apparatus into the bloodstream
list the three factors that stimulate renin release
1) fall in afferent arteriole blood pressure and therefore the renal perfusion pressure, detected by baroreceptors
2) decrease in Na+ load to the top of the loop of Henle detected by the macula densa cells
3) increased sympathetic nervous system activity, detected by the beta-1 adrenergic receptors
which receptors detect a fall in afferent arteriole blood pressure?
baroreceptors
which cells detect a fall in Na+ load at the top of the loop of Henle?
macula densa cells
which receptors detect increased renal sympathetic activity?
beta-1 adrenergic receptors
besides increased aldosterone biosynthesis, what is the main function of angiotensin II?
vasoconstriction
which enzymes are activated by angiotensin II and why?
side-chain cleavage enzyme 3 hydroxysteroid dehydrogenase 21 hydroxylase 11 hydroxylase 18 hydroxylase
= aldosterone biosynthesis
what is the main function of cortisol?
normal stress response
= 1) metabolic effects
= 2) weak mineralocorticoid effects
= 3) renal and cardiovascular effects
what are the metabolic effects of cortisol?
- peripheral protein catabolism
- hepatic gluconeogenesis
- fat metabolism (lipolysis in adipose tissue)
= increased blood glucose concentration
(enhanced effects of glucagon and catecholamines)
what are the weak mineralocorticoid effects of cortisol?
the mineralocorticoid receptor binds both aldosterone and cortisol with equal affinity
(IN EXCESS) when cortisol binds to the MR in the kidney, it (like aldosterone) stimulates sodium reabsorption and regulates blood pressure
what are the renal and cardiovascular effects of cortisol?
renal = excretion of water load
cardiovascular = increased vascular permeability
how does cortisol cause an increase in the excretion of water in the kidneys?
at NORMAL levels, cortisol negatively feeds back to reduce CRH & ADH secretion
so with less ADH, there is less water reabsorption and more water excretion into the tubular fluid
(NB - in EXCESS, cortisol acts on the MR to stimulate sodium and therefore water retention)
explain the negative feedback system involving cortisol
increased cortisol will cause reduced ACTH (pituitary gland) and reduced CRH (hypothalamus)
which enzymes are activated by ACTH and why?
side-chain cleavage enzyme 3 hydroxysteroid dehydrogenase 17 hydroxylase 21 hydroxylase 11 hydroxylase
= cortisol biosynthesis
compare aldosterone regulation to cortisol regulation
aldosterone regulation = renin-angiotensin system (RAAS)
cortisol regulation = negative feedback system with the anterior pituitary gland (ACTH, CRH)
differentiate between cortisol and prednisolone
prednisolone has one more double bond than cortisol giving it
1) a longer half-life
2) increased potency
3) increased binding affinity
what is Addison’s disease?
primary adrenal failure
i.e. direct damage to the adrenal glands impairing aldosterone and cortisol biosynthesis
define primary adrenal failure
when there is direct damage to the adrenal glands impairing aldosterone and cortisol biosynthesis
what are the two possible causes of Addison’s disease?
1) autoimmune damage to the adrenal cortex (commonest cause in the UK)
2) tuberculosis of the adrenal gland (commonest worldwide cause)
why do patients with Addison’s disease appear tanned?
due to impaired levels of cortisol + via the negative feedback system, there is increased ACTH secretion via the APG
increased ACTH requires more POMC to be cleaved: a byproduct of which is aMSH, which stimulates skin pigmentation (i.e. tan)
what are the characteristic symptoms of Addison’s disease?
increased pigmentation (visible tan/bronzing)
autoimmune vitiligo can co-exist
low blood pressure (due to lack of aldosterone & cortisol)
what is a ‘salt-losing Addisonian crisis’?
in Addison’s disease, impaired biosynthesis of aldosterone + cortisol = deficiency
reduced sodium reabsorption and therefore more salt (& therefore water) loss in the urine
= low blood pressure
= eventual death
how can Addison’s disease present both with hyperpigmentation and vitiligo?
hyperpigmentation = increased ACTH requiring more POMC cleavage, producing increased levels of aMSH
vitiligo = can sometimes have autoimmune damage to melanocytes, leading to reduced melanin production so white patches of skin
what are the common symptoms of Addison’s disease?
skin = hyperpigmentation, vitiligo
gastrointestinal = nausea, vomiting, diarrhoea, constipation, abdominal pain
general = low BP, weight loss, weakness
what are the common symptoms of Addisonian crisis?
hyponatraemia, hypoglycaemia, syncope
severe diarrhoea & vomiting
fever
convulsions
describe how an Addisonian crisis is treated
1) rehydrate with normal saline
2) give dextrose to prevent hypoglycaemia that may have been caused by glucocorticoid deficiency
3) give hydrocortisone or another glucocorticoid
why is rehydration with normal saline required to treat an Addisonian crisis?
Addisonian crisis = mineralocorticoid/aldosterone deficiency = reduced salt reabsorption = reduced water reabsoprtion = low blood pressure
!! saline required to correct blood volume deficit and hypotension !!
why is dextrose required to treat an Addisonian crisis?
to prevent/treat hypoglycaemia that may have been caused by glucocorticoid deficiency
(NB - the glucocorticoid, cortisol, has metabolic effects)
what is Cushing’s syndrome?
a condition caused when you have too much cortisol (or another glucocorticoid)
what are the main symptoms of Cushing’s syndrome?
red cheeks moon face fat pad (buffalo hump) easy bruising thin skin red/purple striae centripetal obesity proximal myopathy (muscle wasting) poor wound healing (skin ulcers)
- impaired glucose tolerance (diabetes)
- depression
- high blood pressure/hypertension
- osteoporosis
list four possible causes of Cushing’s syndrome
1) taking steroids by mouth
2) pituitary-dependent Cushing’s disease (pituitary adenoma)
3) ectopic ACTH (lung cancer)
4) adrenal adenoma or carcinoma
what are female and male-specific signs of Cushing’s disease?
females = amenorrhoea, hirsutism
males = erectile dysfunction
from where is the medulla derived from?
ectodermal neural crest cells
what is the main precursor for adrenaline and noradrenaline synthesis?
tyrosine
then converted into dopamine then converted into norepinephrine and then into epinephrine
where are catecholamines stored?
within the neuroendocrine/chromaffin cells of the adrenal medulla
what stimulates catecholamine release from the adrenal medulla?
released from their cytoplasmic granules in response to the acetylcholine from preganglionic sympathetic neurones
what is the function of catecholamines?
‘fight or flight’ response
i.e. tachycardia, sweating, alertness, increased blood glucose, vasoconstriction
how do noradrenaline and adrenaline circulate in the bloodstream?
bound to albumin
which two hepatic enzymes are responsible for catecholamine degradation?
1) monoamine oxidase
2) catechol-O-methyl transferase
how is catecholamine release from the adrenal medulla regulated?
adrenal medulla is under autonomic control
i.e. preganglionic sympathetic neurones that release ACh
