Flashcards in Endo - Adrenal Deck (55)
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1
long term stress response (glucocorticoids)
1. protein/fat converted to glucose or broken down for energy
2. increased blood glucose
3. suppress immune
2
adrenal zones (+hormones)
zona glomerulosa (aldosterone)
zona fasciculata (cortisol + androgens)
zona reticularis (cortisol + androgens)
medulla (E/NE)
3
making E/NE
tyrosine --> dopa --> dopamine --> NE --> E
cortisol needed to make E from NE
4
E:NE release
4x more E
more important for beta 2 receptors
5
embryonic origin of adrenal gland
cortex (mesoderm)
medulla (neuroectoderm)
6
adrenal gland innervation
cortex (nearly none)
medulla (SNS)
7
making aldosterone
rate limiting step: Ang II stimulates cholesterol desmolase (chl to pregnenolone)
pregnenolone --> progesterone
--> deoxycorticosterone (#2 most potent natural MCC)
--> corticosterone
--> aldosterone
8
making cortisol
rate limiting step: ACTH stimulates cholesterol desmolase (chl to pregnenolone)
pregnenolone / progesterone
+ 17 alphahydroxylase
--> --> cortisol
9
making androgens
rate limiting step: ACTH stimulates cholesterol desmolase (chl to pregnenolone)
pregnenolone / progesterone
+ 17 alphahydroxylase
--> --> androgens
10
why is only aldosterone made in ZG? (not cortisol or androgens)
ZG doesn't have 17-alpha hydroxylase
11
things that stimulate cortisol
ACTH
↓ cortisol levels
Stress
ADH
Serotonin
Sleep-wake transition
α-agonists, β-antagonist
12
things that inhibit cortisol
↑ cortisol levels
Opioids
Somatostatin
13
ACTH effects on adrenal gland
stim production of cortisol, adrenal androgens and aldosterone (slightly)
only cortisol feeds back
adrenal gland hyperplasia (via IGF-1)
14
POMC
preproopiomelanocortin is precursor for ACTH
when ACTH is metabolized it makes MSH
15
cortisol release type
pulsatile
constant in amt released, changes in freq
summation for larger pulses
16
cortisol diurnal pattern
ACTH + cortisol peak before waking
lowest before sleep
17
what determines circadian rhythm
suprachiasmatic nucleus
18
things that alter suprachiasmatic nucleus
chronic GCCs (blunt morning peak)
lack of natural light during day, artificial light at night
variable work schedule*
19
cortisol and stress
stress overrides negative feedback
enhance activity of CRH-ACTH system
20
cortisol transport
bound in blood
corticosteroid-binding globulin (CBG, transcortin) - 75%
albumin - 15-20%
unbound 5%
21
cortisol inactivation
takes place in liver
inactivates and conjugates w/ glucuronide or sulfate to up solubility for kidneys
22
cortisol half life
70 min
23
cortisol mech
1. unbind from transport protein
2. enter cell
3. bind to receptor complex (includes HSPs - heat shock proteins)
4. HSPs released
5. receptor binds to DNA
6. regulates gene expression
24
cortisol effects (time)
lag period - need to synth new protein
last a long time - slow protein turnover
25
cortisol actions (broad)
stim gneo in response to low blood sugar
increase protein/lipid breakdown (makes gneo substrates)
anti-inflammatory
suppress immune response
26
cortisol actions (metabolism)
up gneo
up protein/lipid breakdown
inhibits insulin-stimulated gluc uptake by muscle/adipose (like GH)
blocks suppressive effects pf insulin on hepatic glucose output
-----------> provide brain w/ glucose
27
cortisol w/ protein and fat
direct lipolytic effect is small
permissive for lipolytic action of catecholamines
stim appetite
stim lipogenesis in certain spots (face/trunk)
increase protein breakdown up decrease AA utilization everywhere but liver (down protein synth)
28
cortisol and muscles
basal levels of cortisol needed for normal contractility
excess --> atrophy
29
cortisol and bones
decrease bone formation*:
- down vit D synth
- inhibit making osteoblasts
- up apoptosis of osteoblasts/cytes
increase bone reabsorption
- make cytokines --> activate osteoclasts
30
cortisol and CV
basal levels needed for normal BP (permits vessels to respond to adrenergic.angiotensin)
excess -->. hypertension
31
cortisol and kidney
up GFR
inhibit ADH
none --> dehydration (?)
32
cortisol and CNS
receptors: hippocampus, reticular activating substance, autonomic nuclei
affects learning, emotions
excess: insomnia, euphoria or depression
33
cortisol and fetus
stim synth of surfactant
stim maturation of GI enzymes
+ help fetal CNS, retina, skin
34
cortisol and immune
inhibit inflammatory (asthma)
prevents rejection of transplant
vulnerable to infection
35
Cushing's syndrome
hypersecretion of cortisol
ACTH dependent or independent
36
ACTH dependent hypersecretion causes
pituitary microadenoma (Cushing's disease - 80%)
ACTH secreting ectopic tumor (20%)
CRH secreting ectopic tumor (rare)
37
ACTH independent hypersecretion causes
adrenal tumor
iatrogenic - give GCCs for arthritis, allergies, transplants
38
Cushing's syndrome Sx
truncal obesity
moon face
hypertension
skin atrophy
diabetes
gonadal dysfxn
muscle weakness
hirsuitism, acne
mood changes
osteoporosis
39
cushing's syndrome Dx
1. high cortisol in plasma, urine, saliva -- unreliable
2. 24 hr urine cortisol -- screening
3. dexamethasone suppression test
40
Cushing's Dx using DEX (broad)
DEX suppression test
25x higher affinity for cortisol receptors than cortisol
See if cortisol levels drop when DEX is given as a result of negative feedback
41
Cushing's Dx using DEX (steps + results)
1. 2 mg overnight
2. 8 mg overnight
42
Cushing's Dx using DEX (results)
after 2 mg --> normal people cortisol will drop a lot (neg feeddback
after 8 mg --> Cushing's disease will drop 50% (tumor only inhibited by high levels)
after 8 mg --> adrenal tumors won't drop (no feedback)
43
cortisol hyposecretion types
primary adrenal insufficiency (Addison's)
secondary adrenal insufficiency
44
Addison's mech
autoimmune destruction of adrenal cortex -->
deficiencies in cortisol, aldosterone and adrenal androgens
excess ACTH from lack of feedback
45
Addison's Sx
hyperpigmentation (esp @ elbows, knuckles - from excess ACTH --> excess MSH)
weakness
depression
weight loss
hypotension
46
secondary adrenal insufficiency mech
lack of ACTH from drugs or tumors/infections of pituitary gland
deficiency of cortisol but not aldosterone
sluggish response to ACTH due to atrophy
47
secondary adrenal insufficiency Sx
like Addison's (but w/o hyperpigmentation)
mild orthostatic hypotension
poor response to stress
48
adrenal insufficiency Dx
cosyntropin stimulation test
rapid: screening
prolonged: differential
49
cosyntropin stimulation test
cosyntropin is synthetic ACTH
normal: cortisol goes up
primary: cortisol never goes up
secondary: cortisol starts to go up after a long time (sluggish)
50
high cortisol, high ACTH
cushing's disease (pit tumor) or ectopic ACTH tumor
51
high cortisol, low ACTH
adrenal tumor
52
low cortisol, high ACTH
primary adrenal insufficiency (Addison's)
53
low cortisol, low ACTH
secondary adrenal insufficiency
54
congenital adrenal hyperplasia mechanism
21-hydroxylase deficiency -->
no cortisol or aldosterone made
--> up ACTH (no neg feedback)
--> up androgen production
55
