Adrenal Glands Flashcards
What are the 3 main stresses an organsim responds to? [3]
Hypotension
Infection
Starvation
Adrenal Cortex:
Zona [] - adreno androgens. Eg. [].
Zona [] - glucocorticoid hormones eg. []
Zona [] - minerocorticoid hormones eg. []
Adrenal Cortex
Zona reticulars - adreno androgens. Eg. testosterone
Zona fasciculata - glucocorticoid hormones eg. cortisol
Zona glomerulosa - minerocorticoid hormones eg. aldosterone
How is direct communication possible between the adrenal cortex and medulla? [1]
No barrier between the medulla and the zona reticulata - so direct communicaton is possible
The medulla contains [] cells.
chromaffin cells
Cortex – derived from the embryonic [].
Medulla – derived from the [] neural crest cells.
Cortex – derived from the embryonic mesoderm.
Medulla – derived from the ectodermal neural crest cells.
What are the 3 arteries that supply the adrenal glands? [3]
Which arteries do they come from? [3]
Superior adrenal artery – arises from the inferior phrenic artery
Middle adrenal artery – arises from the abdominal aorta.
Inferior adrenal artery – arises from the renal arteries.
Label A-D
A: superior adrenal artery
B: inferior phrenic artery
C: middle adrenal artery
D: inferior adrenal artery
Hyperplasia of the ZF would cause which disease? [1] Because of an overproduction of what? [1]
Cushings disease: high levels of cortisol
Why might you see expansion of ZG in body?
If the Na is low in blood: expansion of the ZG to produce more aldosterone.
All pathways in the steroidogenic enzyme pathway start with which molecule? [1]
Cholesterol: The different enzymes of the different zones allow cholesterol to be turned into di#erent hormones.
Different enzymes expressed in the cortex zones:
ZG: For aldosterone synthesis? [1]
ZF: For cortisol synthesis? [1]
ZR: for testosterone synthesis? [1]
ZG: For aldosterone synthesis: Aldosterone synthase: P450c 11AS
ZF: For cortisol synthesis: p450c 11B-hydroxylase
ZR: for testosterone synthesis: 17a-hydroxylase
What is release of aldosterone stimulated by? [2]
rising K+ [1]
fall in blood volume/BP [1]
ZG cells are distinguished by expression of the type I [] receptor , [] synthase, low levels of [], and no expression of [].
ZG cells are distinguished by expression of the type angiotensin II receptor (AT1), aldosterone synthase, low levels of p450c17 (which produces testosterone) and no expression of p450c11β (which produces cortisol)
Explain hyperaldosteromism affects the RAAS system
Renin converts angiotensin -> ANG1
ANG1 converted to ANGII by ACE (from lungs) ANG II:
Causes direct vasoconstricton + binding to ANG II receptors in ZG
ZG cells produce aldosterone: causes vasoconstriction + remodelling - (ininflammation in heart + vasculature).
Second effect of aldosterone: ‘sodium savour’: Na reabsorption + water reabsorption : Have to exchange K+ at the ENAC channels on the distal tubule.
Aldosterone release triggered by RAAS and high serum K+ levels.
RAAS system is triggered by? [4]
Na loss
haemorrhage
upright posture
decreasing renal blood
Aldosterone binds to [] receptor
Aldosterone binds to mineralocorticoid receptor
The enzyme families that control conversion of cholesterol to adrenal cortex enzymes are? [2]
cytochrome p450
hydroxy-steroid dehydrogenase (HSD) classes.
ZG cells express receptors for [] but the main regulators of secretion of aldoseterone are [] and small increases in the extracellular [] concentration.
ZG cells express receptors for ACTH but the main regulators of secretion are angiotensin II (Ang II) and small increases in the extracellular potassium concentration.
Angiotensin II levels increase because of volume depletion causing renin release in the kidney, but sodium depletion does not seem to cause aldosterone release through this mechanism. Aldosterone release is inhibited by somatostatin, heparin, atrial natriuretic peptide and dopamine
mineralocorticoid receptor is activated by which two substrates? [2]
Why is that important? [1]
mineralocorticoid receptor: activated by cortisol AND aldosterone
So in cells where aldosterone is active, cortisol is deactivated otherwise receptor would be overwhelmed
What is the role of 11β-HSD2? [1]
11 β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2): converts active cortisol to inactive cortisone and protects mineralocorticoid receptor (MR)
Aldosterone renal effects:
Explain MoA of Aldosterone on Principal cell
- Aldosterone binds to MR in tubular cell
- This activates Na/K+ pump on capillary side to pump Na+ out of cell
- Creates an Na gradient -> allows Na+ to flow down ENaC channels on luminal wall. The ENaC channels are also upregulated by aldosterone.
- Potassium is excreted into the lumen due to the K+ gradient created by Na/K pump
- Electrical neutrality maintained by Cl- reabsorpon.
Aldosterone renal effects:
Explain MoA of Aldosterone on Intercalated cell?
Essentially it stimulates and upregulates expression of the ENaC sodium channel in the principal cell, and the Hydrogen ATPase in the intercalated cell. Sodium influx leads to potassium influx.
Aldosterone binds to MR
Activates Na/K pump
H+K+ATPase activated on luminal wall -> loss of H+ into the lumen and excreted
This -> alkalosis.
Aldosterone XS causes which 3 physiological changes? [3]
Hypertension, hypokalaemia and metabolic alkalosis.
What is Conn’s syndrome aka? [1]
Caused by? [2]
AKA: Primary aldosteronism
can occur from a unilateral adrenal adenoma, or from hyperplasia of the ZG of both adrenal gland
What is Liddle syndrome caused by? [1]
What are the symptoms? [3]
C
Caused by: overexpression of ENaC channels
Symptoms: of hyperaldosteronism - Hypertension, hypokalaemia, metabolic alkalosis
Which enzyme being suppressed / mutated causes syndrome of apparent mineralocorticoid excess? [1]
Why does that create symptoms of hyperaldosternism? [1]
When 11BHSD-2 enzyme is supressed/mutated - cortisol isnt deactivated and will binds to MR.
symptoms of hyperaldosteronism
Explain MoA of cortisol being released from hypothalamus to adrenal cortex [3]
What receptor is activated to release cortisol? [1]
Hypothalamus: releases CRH hormone
AP: CRH stimulates release of ACTH from POMC processing
Adrenal cortex: ACTH causes release of Cortisol by binding to melanocortinn-2 receptor in ZF
Specifically, how does ACTH binding to Melanocortin-2 receptor (ACTH Receptor) work? [3]
Upregulation of all enzymes creating cortisol from cholesterol.
Causes release of stored cortisol
Causes hyperplasia of stored cortisol in prep. For further release later on.
Which enzyme is the final step in producing cortisol from cholesterol? [1]
CYP11B1
Explain with condition of glucocorticoid remediable aldosteronism
Fusion of the CYP11B1 promoter to the coding region of CYP11B2 results in** aldosterone production in the Zona Fasciculata**.
Because ACTH normally upregulates the expression of CYP11B1, in this case it also upregulates CYP11B2, leading to aldosterone excess. (AND therefore HTN, hypoK and met. alkalosis)
What can stimulate HPA axis to produce cortisol? [3]
Inflammation
Stress
Circadian rhythm (highest in morning)
What effect does increasing cortisol levels have on HPA axis?
-ve feedback: reduces it
