Adrenal Gland Flashcards
1
Q
cortex
A
- derived from mesoderm
- secretes glucocorticoids, mineralcorticoids, androgens
- essential for life- fatal in 4-14 days if lost
2
Q
medulla
A
- derived from NCC
- epi, norepi. dopa, dopamine
- modified post ganglionic SNS cells
- total loss is not life threatening
3
Q
steroid hormone synthesis in adrenal cortex
A
- starts at cholesterol
- to pregnenolone via 20,22 desmolase (P450 side chain cleavage enzyme)
- rate limiting step
- all enzymes are cyt P450 family except for cytosolic 3-b-hydroxysteroid dehydrogenase
- then a bunch of other enzymes take it to final products
- can get to cortisol in two pathways- through corticosterone (3b, 21a, 11b) and then 17a or use 17-a-hydroxylase first and then go through 3-b-hydroxysteroid DH, 21a and 11 b to cortisol
- see picture please
4
Q
aldosterone synthesis in zona glomerulosa
A
- layer lacks 17-a-hydroxylase, but has aldosterone synthase
- goes from pregnenolone to progesterone with 3-beta- hydroxysteroid DH
- then to 11 deoxycorticosterone via 21a
- then to corticosterone via 11b
- then finally to aldosterone with aldosterone synthase
- only this layer has that enzyme
5
Q
aldosterone
A
- no storage pool of pre-synthesized aldosterone
- once secreted, 37% remains free in the plasma, rest weakly binds to CBG and albumin
- stimulates kidney to reabsorb water and socium and enhance potassium secretion
- increases transcription of Na/K pump and expression of apical sodium channels
6
Q
synthesis of cortisol and androgens in zona fasciculata and reticularis
A
- androgens down from pregnenolone or progesterone (3bDH), then down through 17a, 17,20 desmolase
- cortisol as talked about above (17 first or last, then 3 bDH, 21a, 11b)
- these layers don’t have aldosterone synthase but have 17a
7
Q
DHEA
A
- dehydroepiandroesterone and androstenedione are two adrenal androgens
- far less potent than testosterone or dihydrotestosterone
- andro can be converted to testosterone in peripheral tissues
- DHEA peak production in the 20s, maintains sex drive in females after menopause
8
Q
cortisol transport in plasma
A
- 90% bound to cortisol binding protein
- 7% bound to albumin
- 3% circulates free
9
Q
cortisol mechanism of action
A
- free cortisol enters cell by diffusion
- binds to cytoplasmic receptor
- migrates to the nucleus
- modulates gene transcription
- cortisol inhibits expression of CRH and ACTH in the corticotrophs of ant pit
- inhibits transcription of POMC gene
10
Q
cortisol action
A
- in muscle increases protein degradation and lipolysis
- FA used for work, aa used for proteins elsewhere
- in liver causes increased gluconeogenesis
- blocks glucose uptake except in the brain
- anti-IF and suppresses immune system
- inhibits phospholipase A2, Cox1 and 2, also IL2 and its receptor
- promotes fat deposition in face and trunk
- decreases osteoblastic activity in bone and interferes with calcium absorption in gut
- can cause emotional instability (receptors expressed in the brain)
11
Q
Anti IF action of cortisol
A
- inhibits production of cytokines
- inhibits production of chemo-attractants
- stabilizes lysosomal enzymes
- contributes to vasoconstriction and decreased cap perm
12
Q
immunosuppressive effects of cortisol
A
- decreases lymphocyte proliferation
- inhibits hypersensitivity reactions (histamine release from mast cells)
- inhibits Fc receptor on macrophages
13
Q
analogs
A
- if cortisol potency for glucocorticoid and mineralcorticoid taken as 1 (g and m)
- predisone increases G 3.5-5 and m 0.8
- prednisolone g4, m 0.8
- dexamethasone g 25-80, m 0
- fludrocortisone acetate g 15, m 200
14
Q
cellular action of CRH
A
- exhibits effect on corticotroph
- CRH binds to receptor
- activates Gs, increases cAMP, activates PKA
- PKA P a calcium channel, influx causes release of ACTH
- also causes synthesis of new ACTH
15
Q
cellular action of ACTH
A
- ACTH binds to receptor
- Gs activated, inc cAMP, increase PKA
- PKA increases synthesis of enzymes and activity of P450SCC- the first enzyme in the cholesterol to hormone synthesis pathway
- receptor called melanocortin 2
16
Q
control of cortisol secretion
A
- long feedback-cortisol from adrenal gland inhibits corticotrophs in ant pit (ACTH) and hypothal (CRH)
- short feedback ACTH from ant pit inhibits hypothal
- inhibits POMC gene in ant pit and exocytosis of ACTH
17
Q
CRH and CRH receptor
A
- CRH from paraventricular nucleus
- receptors are G coupled receptors
18
Q
ACTH
A
- comes from POMC gene in corticotroph
- trophic for cortex cells
19
Q
POMC
A
- precursor protein called pro-opiomelanocortin
- ACTH and alphaMSH come from here
- beta lipotropin
- MSH and beta endorphin during pregnancy
20
Q
MSH
A
- melanin stimulating hormone
- anorexogenic
21
Q
diurnal variation in ACTH
A
- highest levels in early morning and lower levels in the evening
- information about light/dark transmitted from retina to suprachiasmatic nucleus of hypothal which controls circadian rhythms of body
- CRH release from hypothal is in pulses, results in pulsatile secretion of ACTH
22
Q
stress and cortisol secretion
A
- physical, psychosocial and biochemical stress enhances CRH secretion and enhanced ACTH secretion which result in increased secretion of cortisol
- hypoglycemia stimulates both, cortisol raises blood glucose levels
23
Q
21-a-hydroxylase deficiency
A
- can’t get to corticosterone or cortisol
- salt losing hypotension/dehydration/ hyperkalemia
- common for genetic disease
- decreased cortisol and aldosterone, increased ACTH, adrenal hyperplasia, increased androgen production, ambiguous genitalia in females
- diagnosis by elevation of 17-hydroxyprogesterone before and after ACTH stimulation test
- molecular analysis of CYP21 gene
24
Q
hormone replacement therapy for 21
A
- glucocorticoids like prenisolone and dexamethason provied reliable sub
- reduces ACTH levels
- reducing ACTH reduces stimulus for hyperplasia
- mineralcorticoids are replaced in all infants with salt wasting and in most patients with elevated renin levels
- fludrocortisone only one available
25
Q
consequences of 21a deficiency
A
- decreased aldosterone- loss of salt, hypotension, dehydration
- decreased cortisol synthesis-hypoglycemia, increased size of adrenal gland
- increased androgen synthesis-virilizing effect in males, ambiguous genitalia in females
26
Q
17 a dehydroxylase deficiency
A
- reduced cortisol and androgens
- increased corticosterone (weak glucocorticoid, mitigates adrenal insufficiency)
- increased aldosterone, hypertension and hyperkalemia
- reduced estrogen synthesis in ovary
-hormone replacement-hypertension and mineralcorticoid excess treated with glucocorticoid replacement, genetic females need estrogen, genetic males need testosterone or surgery
27
Q
clinical features of 17 a deficiency
A
- hypertension
- hyperkalemia
- sexual infantilism in genetic females
- pseudohermaphroditism and sexual infantilism in genetic males
- increased size of adrenal gland due to increased corticosterone
28
Q
cushing’s syndrome
A
- exposed to too much cortisol for long periods of time
- prolonged use of immunosuppressive drugs (prednisone), adrenal tumors, tumors that increase ACTH (pit), ectopic ACTH syndromes
- disease is pit tumor that increases ACTH
- syndrome is excess cortisol of any etiology
29
Q
symptoms of cushings syndrome
A
- moon face, florid complexion, upper body obesity, rounded face, increased fat around the neck, thinning arms and legs
- change in body fat distribution
- skin thinning and fragility
- osteopenia
- increased freq and severity of infections
- muscle wasting and weakness
- glucose intolerance
- hypokalemia and hypertension
- females can grow hair on their face
30
Q
diagnosis of cushing’s
A
- urinary or salivary cortisol measurement
- dexamethason suppression test
- if adrenal tumor, cortisol high and ACTH low
- if ACTH producing tumor, both will remain high
- dexa provides negative feedback- should stop ACTH (if pit tumor secreting, it won’t, if adrenal tumor, it will, but cortisol will stay high because adrenal gland messed up)
- treated with surgery to remove adrenal adenoma or ATCH producing adenoma
- if both adrenals removed need to replace with hydrocortisone
- alternatively can inhibit cortisol synthesis, limited efficacy
31
Q
addison’s disease
A
- hypoadrenal function
- AI, TB, infection
- lack of aldosterone results in hypotension, hyperkalemia
- lack of cortisol results in hypoglycemia, weakness, weight loss and in general a poor tolerance to stress
- primary adrenal disease and increased ACTH causes hyperpigmentation of skin and mucous membranes
32
Q
diagnosis of addisons
A
- determine if levels of cortisol are sufficient
- ACTH stim test- blood cortisol, urine cortisol, or both measured before and after a synthetic form of ACTH given by ijection
- CRH stimulation test- inject CRH, measure cortisol and ACTH before and after
- primary adrenal problem have high ACTH but not cortisol, secondary problem have no ACTH or cortisol
- treat by replacing cortisol and fludrocortisone if necessary for aldosterone
