Adrenal Gland Physiology - Sukimar 117 Flashcards
Most important sex steroids secreted by the adrenals are ____
weak androgens: DHEA-S
RLS of cholesterol break down to pregnenolone
Requires enzyme 20, 22 Desmolase
a cytochrome P450 enzyme
The zona glomerulosa makes aldosterone, while the zona fasciculata makes cortisol (most important glucocorticoid made by adrenal). Why cant the ZG make cortisol if cholesterol breakdown occurs throughout the adrenal cortex?
ZG lacks the enzyme 17a-hydroxylase
which breaks down prenenolone to 17 a-hydroxypregnenolone + breaks down progesterone to 17a-hydroxyprogesterone,
which eventually gets broken down to cortisol.
(pg 318 FA)
Most common congenital enzyme deficiency of adrenal enzyme - presents in infancy (salt wasting) or childhood (precocious puberty)
- effect?
21-hydroxylase
needed for breakdown of both:
Progesterone → → Aldosterone
17-hydroxyprogesterone → Cortisol
defect = neither aldosterone or cortisol is synth + adrenal androgens are increased
Most important glucocorticoid secreted by adrenal cortex
- majority exists in what state?
cortisol - by ZF
- 90% bound to proteins (CBC + albumin)
Binding of glucocorticoids such as cortisol leads to ↑er levels of plasma hormone, what happens to its biological activity?
Unchanged. BC it is the [ ] of free hormone (set point) that is regulated and active.
Important actions of glucocorticoids
(glucose mobilization)
- stimulation of gluconeogenesis in liver
- Increased proteolysis in muscle and other soft tissues:
- providing aa substrates for gluconeogenesis
- Great for maintaining/elevating blood glucose in times of stress
Hallmark of high levels of cortisol for prolonged periods
muscle weakness
Other: BIGFIB (319 FA) B: ↑ BP I: ↑ Insulin resistance G: Gluconeogenesis (Lipolysis, proteolysis) F: ↓ Fibroblast activity (striae, ez bruising, thin skin) I: ↓ Inflammatory and Immune response B: ↓ Bone formation (osteoporosis)
ACTH effects on cortisol secretion
(+) feedback on cholesterol desmolase
- ACTH → elevated cAMP → increase rate of pregnenolone
Increases LDL uptake
Interacts with cells of ZF to promote cortisol secretion.
Effects of stress on cortisol levels
overrides neg feedback of cortisol on Hypothalamus (CRH) and pituitary (ACTH)
Increases cortisol production up to 40x
Which is more potent, adrenal androgens or testes derived androgens?
Testes (duh)
But in females it is the major source of H with androgen like activity.
Why are adrenal androgens imp for females?
Libido
Growth of pubertal hair
Major stimulus for aldosterone secretion is ____. Which also happens to be a powerful pressor agent.
Angiotensin II
(remember aldosterone is regulated by RAS)
AGII is also a powerful pressor (Increase BP)
*Renin is secreted by JG apparatus in response to ↓ plasma volume or sodium
Addison’s disease
Chronic Primary adrenal insufficiency
- due to adrenal atrophy or destruction by disease
(autoimmune, TB, Metastasis, fungal disorder)
- life threatening
- both mineralocorticoid and glucocorticoid secretion is deficient
- mucosal HYPERpigmentation (Due to MSH, a byproduct of ↑ACTH prod from pro-opiomelanocortin)
(cushings disease is a ACTH secreting pit adenoma which can stimulate mc and gc prod)
Sx of adrenal insufficiency
weakness, fatigue, orthostatic hypotension, muscle aches, GI disturbances, sugar/salt cravings (hyponatremia), HYPERkalemia
- note that only primary adrenal insufficiency has muscosal hyperpigmentation, not secondary or tertiary
- secondary Spares the skin
Secondary adrenal insufficiency
ACTH insufficiency
- only glucocorticoids needs to be replaced
(aldosterone synthesis is preserved)
Hyperaldosteronism due to 2 possibilities
sx?
- tumor of adrenal cortex (primary)
- inappropriately high activity of RAS (secondary)
Hyperadolsteronism
HYPO kalemia
Alkalosis
What is the most common cause of Cushing syndrome? What is responsible for majority of endogenous causes of Cushing syndrome.
Most common: Exogenous steroids
Endogenous cause: Cushing disease - ACTH secreting pituitary adenoma
Other cause: primar y arenal adenoma, hyperplasia, carcinoma
2 tests to differentiate betwn the Difference betwbtwn Cushing disease and Ectopic ACTH secretion when ACTH is elevated >20pg/ml
- High dose dexamethasone suppression test
- adequate suppression = Cushing - CRH stimulation test
- ↑ ACTH, cortisol = Cushing
Development of adrenal medulla
- time period
Derived from neural crest
~7 weeks of gestation, neuroectodermal cells of neural crest invade the primitive cortex and develop into medulla
Medulla is basically a specialized sympathethic ganglion
What are adrenal chromaffin cells, and why are they called that?
They are cells of the medulla and bind chromium dyes
Stimulated by cholinergic pregang. fibers of SNS.
They release EPI and NE
There are two classes of adrenergic receptors a + b. Which one does Epi and Norepi act on?
Epi: activates B-adrenergic receptors
- stim adenylyl cyclase → cAMP
Norepi: activates a-adrenergic receptors
- a1: activ Gq/PLC
- a2: activ Gi
What can trigger the rapid response of EPi
Danger, Trauma, Pain
Physiological stressors:
Hypotension, hypoglycemia, exercise
Activate cholinergic fibers in the greater splanchnic nerve
