17 | Adrenal Gland Flashcards
1
Q
fetal adrenal
A
relatively bigger for body size
large steroidogenic fetal zone
2
Q
embryological origins
A
- adrenal cortex: mesoderm
- adrenal medulla: neuroectoderm (modified S-ANS)
3
Q
adrenocorticoids
A
- adrenal cortical hormones
- derive from cholesterol
- specific product based on stimuli and cell enzymes
- rate limited by cholesterol to pregnenolone
4
Q
StAR
A
[steroid acute regulatory protein]
- production promoted by stimulating factors
- StAR stimulates transport of cholesterol from cytosol to mitochondria
- in mitochondria, enzymes to yield prenenolone
5
Q
mineralocorticoid vs. glucocorticoid
A
typically:
- mineralocorticoid: aldosterone
- glucocorticoid: cortisol
- high levels of each produces alternate effect
- cortisol can readily bind to and activate MC rec
- but MC tissues contain enzyme that converts cortisol to cortisone, reducing mC effects
6
Q
steroid secretion
A
- de novo synthesis
- can’t be stored
- lipid soluble, diffuse across membrane down concentration gradient into circulation
7
Q
steroids in circulation
A
bound to plasma binding proteins -transcortin OR -corticosteroid binding globulin (CBG) AND -albumin
- binding of GCs favored over MCs, cortisol has longer half life than aldosterone (90 vs. 30 min) in the plasma
- though stable DHEAs have far longer half life (15 hrs) and far higher plasma concentrations
8
Q
steroid hormone clearance
A
liver and kidney
9
Q
mineralocorticoid receptors
A
cytosolic
Type I
-mostly in kidney, colon, sweat, salivary glands
10
Q
glucocorticoid receptors
A
cytosolic
Type II
-various tissues of the body
11
Q
ACTH (role in cortisol + androgen production)
A
- derived from POMC (pro-opiomelanocortin)
- ACTH is required for function of zona fasiculata and zona glomerulosa
- circulating level is controlling factor for cortisol and androgen synthesis
- binding increases cAMP that leads to StAR production
- can bind to receptors on all 3 cortex layers
12
Q
circadian rhythm/sensitivity
A
CRH + ACTH subject to feedback inhibition from cortisol
AM: low sensitivity, less negative feedback, higher CRH/ACTH/cortisol
PM: higher sensitivity, more inhibitory feedback, less CRH/ACTH/cortisol
(stress can override diurnal rhythm)
13
Q
cortisol - “stress hormone”
A
necessary for:
- vital functions during times of prolonged stress (mostly physiological)
- permissive function, hormone doesn’t initiate change, but is required for full expression of change
- can be protective
14
Q
cortisol + catecholamines
A
-cortisol req. for catecholamines to be effective, increased catecholamine responsiveness to cortisol responsible for many effects of cortisol
15
Q
++cortisol - blood glucose
A
high cortisol increases BG (glucocorticoid)
-through mechanisms that oppose insulin (wants to store glucose)
16
Q
++cortisol - catabolism
A
high cortisol promotes catabolism
- breakdown of protein from muscle and CT to free AAs for gluconeogenesis (increasing BG)
- also stimulates gluconeogenic enzyme production in liver
17
Q
++cortisol - glucose use
A
high cortisol decreases glucose use
-inhibits glucose transport into cells (increasing BG)
(not in brain)
18
Q
++cortisol - protein synthesis
A
high cortisol decreases protein synthesis everywhere except liver
- reduced AA uptake into muscle
- increased protein catabolism
- plasma AA levels rise (can be used for glucose synthesis)
19
Q
++cortisol - fat metabolism
A
high cortisol increases lipolysis to liberate fatty acids and glycerol for gluconeogenesis
-but increases central fat deposition, while periphery loses fat and muscle mass
20
Q
++cortisol - CNS
A
high cortisol
- feedback inhibition of CTH and ACTH
- perception effects (deficiency can lead to accentuation of senses)
- initial euphoria then depression
21
Q
cortisol - cardiovascular effects
A
cortisol is required to maintain the CVS
- maintains sensitivity to Epi/NE
- w/out vasodilation and decreased BP
22
Q
cortisol - developmental effects
A
permissive in maturation of fetal organ systems, intestinal enzymes, pulmonary surfactant
23
Q
cortisol - renal effects (primary, secondary)
A
free water clearance
- hypothalamic neurons secreting CRH also release ADH
- cortisol feedback inhibition both
- without cortisol, increased CRH and ADH
- increased ADH, inc H20 reabsorption, dec free water clearance (even with decreased plasma osm)
- hypotension secondary to low adrenergic receptors without cortisol also increases ADH levels
- together can cause water intoxication
24
Q
cortisol - bone effects
A
promotes bone breakdown
-in excess enhances osteoclast activity, promoting osteoporosis development
25
cortisol - immune function
contains inflammatory response
- in high doses, suppresses inflammatory response
- used in synthetic GC's (prednisone)
- stabilizes lysosomal membranes, dec capillary permeability, dec phagocyte activity, suppression of IL-1, inhibits eicosanoid production (PGs, leukotrienes)
26
cortisol elimination
filtered in glomerulus, appears in urine
| also reduced and conjugated in liver, metabolites filtered
27
adrenal androgens - relative production
- large quantities in fetus, important during fetal development
- postnatally low, but rises during prepuberty (onset of hair growth and secretion)
28
adrenal androgens - females
- major androgen source in adult females
- converted to testosterone in periphery, contribute to axillary/pubic hair growth
- some androstenedione converted in periphery to estrogen, major source of E post-menopause
29
DHEA levels
- similar to cortisol as young adult
- decline with age
- DHEA-S filtered and excreted
30
aldosterone function
-increase Na reabsorption in distal nephron, inc K+ secretion
(increased Na/K pump activity, and number of rec)
-production due to ANII + plasma K+ levels
- ANII produced due to increased renin from fall in AA perfusion pressure or by S-ANS stimulation
- renin influenced by Na+/Cl- at MD, electrolyte levels, ANII feedback
31
aldosterone production
- stimulated by ANII by cells of zona glomerulosa
- increased intracellular 1,4,5-triphosphate, increases StAR
- levels also inc by inc. E (pregnancy), increased PV
32
hyperaldosteronism
hyposmotic sweat and saliva
33
adrenal medulla - structure
- cells are modified postganglionic S-ANS neurons
- innervated by splanchnic nerves
- chromaffin cells w/ secretory granules
34
chromaffin granules
store catecholamines
5:1 epi:norepi ratio
ATP also present 1ATP:4catecholamines
35
catecholamine synthesis
tyrosine to DA to norepineprhine
NE mostly converted to epi
-catalyzed by PNMT, which is inducible by cortisol
-medulla receives blood from cortex, rich in corticosteroids. cortisol can fine tune epi:NE ratio
36
granule release
- secreted in response to S-ANS *ACh/cholinergic stimulation (NOT andrenergic - NE/E)
- ACh binding, inc Ca2+ levels, promote exocytosis
37
catecholamines in circulation
50% free in solution, 50% loosely w/ albumin
- rapidly cleared (10-15s)
- taken up by neurons, repackaged or inactivated by MAO
- non-nueronal tissue, inactivated by MAO or COMT
- degradation products coupled with sulfate/glucuronic acid, excreted in urine
-almost all epi in circulation adrenal, but circ NE from other sympathetic synapses
38
catecholamine receptors/function
- equally effective on B1
- NE is potent a agonist, little effect on B2
- E is more potent a agonist, powerful on B2
39
catecholamine effects
stimulate gluconeogenesis, glycogenolysis, lypolysis
-increase BG and FFA levels
-increase CO
in excess: hypertension, headache, anxiety, sweating, palpitations, chest pain, postural hypotension)
40
adrenal gland organization
```
[cortex - all steroid hormones]
glomerulosa: mineralocoritcoids (aldosterone)
fasciculata: glucocorticoids (cortisol)
reticularis: adrogens, DHEA
[medulla]
catecholamines (E, NE)
```
41
prednisone
synthetic glucocorticoid
acts as a pure GC, no mineralocorticoid effects
(can be used to promote surfactant development in fetus)
42
long term prednisone - immune function
depressed immune function (may be goal)
- inhibition of cytokines, leukotrienes, PGs (inflammatory response mediators)
- depress lymphocyte and monocyte proliferation
43
long term prednisone - blood sugar levels
cortisol normally acts to increase BG
- BG elevated
- since GCs have diabetogenic/counter insulin effects, may show similar symptoms
44
long term prednisone - blood pressure
cortisol required for CVS response to catecholamines
| -increased blood pressure, increased sensitivity
45
long term prednisone - physical appearance
(symptoms associated with Cushing's syndrome)
- moon face, buffalo hump, central obesity/fat deposition
- thinned limbs (peripheral fat and muscle breakdown)
- easy bruising (loss of CT supporting microvasculature)
- high glucose levels (hyperglycemia), thus also hyperinsulinemia
- stimulated appetite, overeating (hyperphagia)
46
Cushing's syndrome vs. disease
- syndrome: excess GC activity (i.e. w/ prednisone)
| - disease: pituitary tumor that leads to overproduction of ACTH, and thus oversecretion of cortisol from adrenal galnd
47
long term prednisone - long term consuences
- decreased renal Ca2+ reabsorption, decreased GI uptake of Ca2+ . w/ dec plasma Ca2+, increased PTH to try and raise
- increased bone reabsorption, increased risk of osteoporosis
- GC promotes gastric secretions, peptic ulcers. also lack of PGs which provide mucosal protection.
- impaired sleep and memory (CNS)
48
long term prednisone - consequence of prompt cessation
- circulating prednisone inhibits CRH, ACTH, cortisol
- zona fasciculata and reticularis will have atrophied
- with immediate stop, no time for these to grow and patient would have little to no glucocorticoid levels (adrenal insufficiency)
49
high endogenous vs. exogenous cortisol
| [hypertension]
endo: cortisol has some MC activity, normally controlled by enzyme at rec. not adequate in excess.
- physiological response of aldosterone
- may have higher BP than w/ high exogenous cortisol, increased water retention
50
high endogenous vs. exogenous cortisol
| [ACTH levels]
- endo: high endogenous cortisol due to ACTH-producing pituitary tumor
- exo: negative feedback from cortisol, very low levels of ACTH
51
high endogenous vs. exogenous cortisol
| [sex hormones]
ACTH stimulates zona fasciculata to produce androgens
- exo: have low ACTH, low androgens
- in women excess exogenous cortisol can lead to body hair growth (hirsutism), deep voice, acne
52
Addison's disease
destruction of adrenal gland
- unable to produce aldosterone, androgens, cortisol
- can be triggered by illness, trauma, or significant stress
- high levels of ACTH, no negative feedback
53
Addison's disease - biological effects
- no cortisol: decrease CVS sensitivity to catecholamines, decreased GC activity
- no aldosterone: increase Na+ loss, hyponaturemia. low ECF vol and PV.
- with hyponaturemia, can have hyperkalemia
- cortisol normally maintains BG, may be hypoglycemic
54
Addison's disease - hyperpigmentation
high levels of ACTH, increased a-MSH levels
| -melanin darkens skin
55
Addison's disease - hypotension
without aldosterone, decreased Na+ and water reabsorption
- low plasma volume, leads to hypotension
- also have low TPR, venous tone, cardiac contractility, catecholamine sensitivity
56
apparent mineralocorticoid excess
- symptoms: high BP, hypokalemic, alkalosis, low Na+ secretion
- symptoms of hyperaldosteronism
- BUT have low aldosterone, and high cortisol levels
- genetic defect, no enzyme to degrade cortisol at MC receptor
- would treat with pure GC to induce negative feedback on ACTH, or inhibition of MC receptor
57
phenochromatoma
tumor of chromaffin cells, excessive amounts of catecholamines
- increased peripheral resistance, tachycardia, vasoconstriction
- hypertension, headaches
- weight loss
- increase blood glucose levels (counter insulin effects)
